Diazo Chemistry, Vol. 2, Aliphatic, Inorganic and Organometallic Compounds

H. Zollinger

Diazo Chemistry II

VCH Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

© VCH Verlagsgesellschaft mbH, D-69451 Weinheim (Federal Republic of Germany), 1995 Distribution: VCH, P. O. Box 101161, D-69451 Weinheim (Federal Republic of Germany) Switzerland: VCH, P. O. Box, CH-4020 Basel (Switzerland) United Kingdom and Ireland: VCH (UK) Ltd., 8 Wellington Court, Cambridge CB11HZ (England) USA and Canada: VCH, 220 East 23rd Street, New York, NY 10010-4606, (USA) Japan: VCH, Eikow Building, 10-9 Hongo 1-chome, Bunkyo-ku, Tokyo 113 (Japan) ISBN 3-527-29222-5

Heinrich Zollinger

Diazo Chemistry II Aliphatic, Inorganic and Organometallic Compounds

Weinheim • New York Basel • Cambridge • Tokyo

Prof. Dr. Drs. h. c. Heinrich Zollinger Technisch-Chemisches Laboratorium Eidgenossische Technische Hochschule CH-8092 Zurich Switzerland

This book was carefully produced. Nevertheless, author and publisher do not warrant the information contained therein to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate. Published jointly by VCH Verlagsgesellschaft, Weinheim (Federal Republic of Germany) VCH Publishers, New York, NY (USA) Editorial Director: Dr. Thomas Mager Production Manager: Dipl. Wirt.-Ing. (FH) Hans-Jochen Schmitt

Library of Congress Card No. applied for. A catalogue record for this book is available from the British Library. Die Deutsche Bibliothek - CIP-Einheitsaufnahme Zollinger, Heinrich: Diazo chemistry / Heinrich Zollinger. - Weinheim ; New York ; Basel; Cambridge ; Tokyo : VCH. 2. Aliphatic, inorganic and organometallic compounds. -1995 ISBN 3-527-29222-5 © VCH Verlagsgesellschaft mbH, D-69451 Weinheim (Federal Republic of Germany), 1995 Printed on acid-free and chlorine-free paper. All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form -by photoprinting, microfilm, or any other means -nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law. Composition: Filmsatz Unger & Sommer, D-69469 Weinheim. Printing: betz-druck Gmbh, D-64291 Darmstadt. Bookbinding: GroBbuchbinderei J. Spinner, D-77831 Ottersweier Cover design and composition of chemical formulas: Graphik & Text Studio Dr. Wolfgang Zettlmeier, D-93164 Laaber-Waldetzenberg. Printed in the Federal Republic of Germany

Dedicated in friendship to RolfHuisgen

Preface

As the title of this book indicates it is a continuation of Diazo Chemistry /, which was finished ten months ago and which contains the chemistry of aromatic and heteroaromatic diazo compounds. The general principles discussed in the Preface of that book are also the basis for this volume. The most important principle is again generality, readability and many references for the reader who is interested in more detailed information. To convey knowledge, to become acquainted with new ideas a delicate equilibrium between selection and redundancy is necessary. Redundancy has its place, particularly for results that are unexpected for the reader or that are in contrast to his experience. In recent decades all branches of science have become increasingly specialized and "disciplined". I hope that I found a way of describing the peculiar in such a way that allows the general to shine through. This should help to follow the main sequence of describing - interpreting - understanding nature as much as possible. There is a French saying that some art is 'Tart pour 1'art" instead of "Part pour rhomme". This saying must also be applied to the two volumes of Diazo Chemistry, for example, in the art of disregarding a good scientific publication at the appropriate place - even if the authors may be disappointed at not finding their names in a certain part of these two books. I am aware, however, that my choice of subjects is biased. When I mention art, this indicates not only some relation between art and scientific book writing, but with science in general. That relation may have been realized by the French painter Delacroix who said: "What I demand is accuracy for the sake of imagination". Accuracy and imagination are indeed both characteristic, not only for art, but also for science. I think that this statement is even justified on the basis of Platon's ideas. He discovered first that what he called philo-sophia, i.e., thinking developed from that great power that the Greeks called eros and, second, that thinking can be understood only if eros is included. The later European tradition has, however, forgotten that origin to a large extent. Yet, sympathetic understanding and intuition are, in my opinion, a part of the eros side of scientific thinking and reasoning. Therefore, I have also neglected in this book three taboos of conventional scientific writing at a few, but appropriate, places, namely the use of "I" instead of "we" or the passive voice, of metaphors, and of narrative style. The chemistry of diazo and diazonium compounds is generally assumed to be completely a domain of organic chemistry. I came, however, to the conclusion that there are new, interesting and meaningful correlations with the inorganic diazonium salts, the transition metal complexes with organic diazo and diazonium ligands, and even with dinitrogen complexes and nitrogen fixation. They justify a joint and comparative discussion with organic diazo chemistry. I am aware that under the title Diazo Chemistry III have covered areas that have not previously been included in

VIII

Preface

a book on that subject. Some readers may think these excursions stray too far. Such raids are, however, not predatory incursions although they led me outside my usual sphere of experimental activity. There may even be organic chemists who not only have little interest in the inorganic parts of this book, but who may criticize the fact that I included them, and that inclusion of aliphatic diazo chemistry is, in their opinion, already outside my personal proper limits, because some 90 percent of my diazo publications are in aromatic chemistry. How shall I answer such criticisms? I may quote G. Binnig, Nobel Laureate in Physics (1986), who said at a symposium in the Swiss Alps in 1993 that interest outside one's proper area is a condition against sterile expertism and for obtaining new ideas. I also remember, however, a short curriculum I had to write for a booklet on the Chemistry Department at ETH (Kisakiirek, 1994). The editor told the authors not to provide data in a Who-is-Who style, but in a more personal manner. In my curriculum I wrote one sentence saying that I learned the style and techniques of physical organic chemistry in the 1940's and 1950's from Gerold Schwarzenbach, Christopher K. Ingold and Paul D. Bartlett. One of them was an inorganic chemist (Schwarzenbach) and Ingold became interested in the stereochemistry of inorganic coordination compounds in his later years and led to the IUPAC Cahn-IngoldPrelog rules of stereochemical nomenclature! Therefore, I may apply the German proverb to myself "Der Apfel fallt nicht weit vom Stamm" (The apple does not fall too far from the tree). Organic diazo chemistry is, however, also growing in its own limits; it is still far from reaching maturity. This is evident in the large Chapters 6, 7 and 8, the subjects of which were treated either only briefly in my first diazo book in 1961 (deamination of amines) or not at all (dipolar cycloadditions, carbenes and carbenoids based on diazo compounds) because they were practically unknown at that time and, surprisingly enough, they were either not treated in diazo monographs in the 25 years after 1961 or with little originality. The literature was checked systematically until early Autumn 1994, including some papers published later, of which I had copies of the manuscripts from the authors. Some important papers, published late in 1994 after the manuscript of this book had already been submitted to the publisher, could be mentioned briefly in footnotes or by adding corresponding statements ("very recent paper"). I dedicated Diazo Chemistry I to Paul D. Bartlett, in part for the reason mentioned above. This volume is dedicated to Rolf Huisgen. He and I are about the same age. Studying chemistry in Germany and in Switzerland, respectively, at a time when the borders of our countries were closed and our knowledge of international science remained at the status of 1939, we had to find our own ways after the war. We came to diazo chemistry from different sides. Huisgen concentrated for quite some time on diazoalkanes (see his autobiography, 1994, pp. 21 and 28). His review in 1955 became a landmark of understanding that there are significant properties of diazoalkanes that can be understood on the basis of physical organic chemistry, properties that are in part different from those of aromatic compounds. And five years later he became the father of dipolar cycloaddition! With that work he demonstrated that one can successfully apply knowledge on diazoalkanes to a large number of analogous 1,3-dipolar reagents.

Preface

IX

I am grateful that I have been able to finish work on this book in spite of rny increasing age. I am very thankful to many colleagues who answered questions I had in discussions and by writing. Their number is too large to be mentioned (besides the fact that I would be embarrassed if I forgot any of them!). I must mention, however, three of my colleagues at ETH, F. Diederich, D. Seebach, and L. M. Venanzi, as well as those colleagues who were kind enough to read certain chapters or sections of the manuscript and to discuss their comments with me during visits to their universities in 1992 and 1993. Their work helped me to improve the quality of this book. They are Profs. J. Fishbein (Wake-Forest University, Winston-Salem, NC), R. Glaser (University of Missouri at Columbia), W. Kirmse (Ruhr-Universitat, Bochum), R. A. Moss (Rutgers University, New Brunswick, NJ), T.T. Tidwell (University of Toronto) and E.H. White (Johns Hopkins University, Baltimore, MA). I thank Professor Kirmse also for his kind offer to write a section (Summary and Outlook) for the deamination chapter. Very decisive for improving the quality of this book was again the help that I received from my former coworker Dr. M. D. Ravenscroft (now with Dow Deutschland Inc., Rheinmiinster) in order to make my English more understandable and for many suggestions concerning the content, and from Dr. M.V Kisakiirek, Managing Director of Helvetica Chimica Act a Publishers, who also read the manuscript critically. In particular he checked the nomenclature, a problem that became urgent because the new Guide to the IUPAC Nomenclature of Organic Compounds (IUPAC, 1994 a) only became available after the manuscript was finished. I thank again Mr. J. Meienberger, Head of the Chemistry Library of ETH for his help in database literature searching, and two former secretaries, Mrs. S. Braun and Mrs. M. Gray, who typed the whole manuscript, and Dr. P. Skrabal, who helped me read the galley and page proofs. He found not only many misprints that I missed, but he came across several scientific errors in my text. As mentioned in volume I, I am very grateful to my wife Heidi for understanding my activities for this book. I will close with a quotation of the poet T. S. Eliot (1888-1965): "The only wisdom we can hope to acquire is the wisdom of humility; humility is endless". Kiisnacht, Zurich, September 1994

Heinrich Zollinger

Contents

Symbols, Quantities and Units XV Abbreviations and Acronyms XVI 1 Introduction 1 1.1 1.2

History of Aliphatic, Inorganic, and Organometallic Diazo Compounds 1 Nomenclature and General References 5

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds 11 2.1 Stable Aliphatic Diazonium Ions 11 2.2 Introduction to the Methods for the Synthesis of Aliphatic Diazo Compounds 15 2.3 Preparation of Aliphatic Diazo Compounds by Nitrosation of Aliphatic Amines 20 2.4 Cleavage of TV-Alkyl-Af-nitroso Amides 28 2.5 Syntheses Starting with Ketones or Aldehydes 34 2.5.1 Dehydrogenation of Hydrazones 34 2.5.2 Bamford-Stevens Reaction 40 2.5.3 Forster Reaction 46 2.5.4 Miscellaneous Reactions 47 2.6 Diazo Transfer to Active Methylene Compounds 48 2.7 Diazo Transfer to Alkenes 63 2.8 Diazo Transfer to Alkynes 75 2.9 Diazoethene and its Derivatives 81 2.10 Synthesis of Alkenediazonium Salts 83 2.11 Synthesis of Compounds with a Csp-attached Diazonio Group 91 3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand 95 3.1 Addition Products of Dinitrogen to Nonmetallic Inorganic Species 95 3.2 Diazo Derivatives of Polyhedral Boron Hydrides 101 3.3 Addition Products of Dinitrogen to Transition Metal Complexes 107 3.4 Short Review on the Chemistry of Nitrogen Fixation 114 4 Kinetics and Mechanism of Aliphatic Diazotizations 121 4.1 Nitrosation of Alkylamines 121 4.2 Carcinogenicity of 7V-Nitrosoamines 127

XII

Contents

4.3 4.4

Mechanisms of Diazoalkane Syntheses 132 Acid-Base Equilibria of Aliphatic Diazo Compounds 138

5 The Structure of Aliphatic Diazo Compounds 145 5.1 5.2 5.3 5.4

Aliphatic Diazonium Ions 145 Diazoalkanes and Related Compounds 146 Theoretical Investigations on Aliphatic Diazonium Salts, and on Alkane, Alkene, and Alkyne Diazo Compounds 161 Isomers of Diazomethane 173

6 Reactions of Aliphatic Diazo and Diazonium Compounds not Involving Initial Dediazoniation 191 6.1 6.2 6.3 6.4 6.5

Azo Coupling Reactions of Aliphatic Diazonium Ions and Related Processes 191 Introduction to 1,3-Dipolar Cycloadditions 195 Mechanism of 1,3-Dipolar Cycloadditions 200 Regio- and Diastereoselectivity of Dipolar Cycloadditions with Diazoalkanes 212 Cycloaddition Reactions with Diazoalkanes in Organic Synthesis 228

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates 241 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8

Introduction to Deamination Mechanisms 241 Routes to Alkanediazonium Ions 244 Deamination Mechanisms of Open-Chain Amines: Substitution Products 253 Eliminations and Rearrangements in Deamination of Open-Chain Amines 271 Deamination of Alicyclic Amines 278 A Challenge to Revisit Deamination Mechanisms 290 Synthetic Applications of Deamination Reactions 295 Summary and Outlook (by Wolfgang Kirmse) 302

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates 305 8.1 Introduction to General Carbene Chemistry 305 8.2 Formation of Carbenes and Carbenoids by Dediazoniation of Diazoalkanes 314 8.3 Addition of Carbenes to Alkenes 318 8.4 Addition of Carbenes and Carbene Precursors to Aromatic Hydrocarbons and to Fullerene[60] 324 8.5 Insertion, Abstraction, and Rearrangement Reactions of Carbenes 335 8.6 Carbenes from a-Diazocarbonyl Compounds: The Wolff Rearrangement and the Arndt-Eistert Reaction 344 8.7 Transformations Involving Metal Carbenoids 358 8.8 Enantioselective Reactions of Carbenoids 373

Contents 9 Miscellaneous Reactions Involving Diazo and Related Compounds 383 9.1 9.2 9.3 9.4 9.5

Electrophilic and Nucleophilic Substitution at the C(a)-Atom of Diazo Compounds 383 The N08)-Electrophilicity of Aliphatic Diazo Compounds 395 Electron Transfer to and from Diazo Compounds: Ion Radicals 400 Oxidations and Reductions of Diazo Compounds 408 Dediazoniations of Alkenediazonium Ions 414

10 Metal Complexes of Diazonium and Diazo Compounds 421 10.1 10.2 10.3

Structure of Metal Complexes Containing Arenediazonium Ions as Ligands 421 Synthesis of Aryldiazenido Metal Complexes 430 Diazoalkanes as Ligands in Transition Metal Complexes 439

11 Epilogue: From Peter Griess' Discovery to Organometallic Diazo Compounds 455 References 459 Index 507

XIII

Symbols, Quantities and Units

D Ea Em EI, E2, £diss / AGf° AH? H0 / k K LD50 PA 5 e \

kJ mol'1 V kJ mol"1 mdyn/pm kJ mol'1 kJ mol'1 Hz * * mg kg'1 kJ mol'1 ppm L mol'1 cm'1 nm

dipole moment Activation energy or enthalpy redox potential kinetic energy valence force constant free energy of formation free enthalpy of formation Hammett acidity function NMR coupling constant reaction rate constant equilibrium constant lethal dose for 50 % population proton affinity chemical shift (NMR) extinction coefficient wavelength (UV)

* Units (mol, s) depending on kinetic order (k) and stoichiometry (K).

Abbreviations and Acronyms"

BNOX CAMEO CID, CISD CIDNP cmc D CC DDQ DIBAL-H 4-DMAP DMNNG EHMO EXAFS FAB MS FMO HMO IGLO IPOX MNDO MNNG MPOX OCAMS PMO QCISD, QCISDT SCF TEMPO TIPPS VZPE

:

benzyl-2,3,4,5-tetrahydrooxazol-2-one computer-assisted mechanistic evaluation of organic reactions configurational interaction theory chemically induced dynamic nuclear polarization critical micelle concentration dicyclohexylcarbodiimide 2,3-dichloro-5,6-dicyano-l ,4-benzoquinone diisobutyl aluminum hydride dimethylaminopyridine A^Af''-dimethyl-Ar''-nitrosoguanidine extended Hiickel molecular orbital extended X-ray absorption fine structure fast atom bombardment mass spectrometry frontier molecular orbital Hiickel molecular orbital individual gauge for localized orbitals 4-isopropyloxazol-2-one modified neglect of differential overlap A^methyl-Af'-nitro-Af-nitrosoguanidine 4-methyl-5-phenyloxazol-2-one orbital correspondence analysis in maximum symmetry perturbation molecular orbital quadratic configurational interaction theory self-consistent field 2,2,6,6-tetramethylpiperidin-l-oxyl 2,4,6-triisopropyl benzene sulfonyl vibrational zero-point energy

Abbreviations and acronyms used only once are explained where they are mentioned.

1 Introduction

1.1 History of Aliphatic, Inorganic and Organometallic Diazo Compounds The beginning of diazo chemistry is generally dated to 1858 when Peter Griess discovered and identified the first aromatic diazo compound. Griess investigated this class of compounds during the following two decades (see reviews by Saunders and Allen, 1985, Zahn, 1989, and Zollinger, 1994, Sect. 1.1). Transient diazonium ions had been obtained, however, ten years before the discovery of Griess, but it took many years until their formation was established. In 1848 Piria treated two aliphatic amines with nitrosating reagents in water and found that the amino group was replaced by a hydroxy group * (see Sect. 2.1). The first aliphatic diazo compound was isolated much later, namely in 1883 by Theodor Curtius (1857-1928). He obtained diazoacetate 1.2 by diazotization of aminoacetate 1.1. Diazoacetate was the first diazoalkane (Scheme 1-1). H2N—CH2—COOEt + HNO2

(1-1)

HO—CHg—COOEt

* It must be emphasized that Piria was unable to describe this reaction in the way that we now express it, as concepts such as substituent, functional group, etc. were still unknown at that time. Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

2

1 Introduction

It became clear much later that diazoalkanes are obtained only if deprotonation of the metastable diazonium intermediate is faster than the dediazoniation or, in other words, if the C(a)-H bond is less stable than the C(a)-N(a) bond. This is the case for aliphatic amines containing a C(a)-atom substituted by an acidifying group. Diazoalkanes lacking such substituents must be prepared by other methods. Diazomethane was first obtained by von Pechmann in 1894 from 7V-methyl-7Vnitroso carbamate (1.3) in ether with methanol and K2CO3 (1-2). Under these conditions, deprotonation of the TV-methyl group takes place first and the carbanion-like C-atom formed has a stabilized bond to the N(a)-atom (see Sects. 5.2 and 5.3). NO

CHoOH-K2CO3

HO

\

ROOC— RO

CH3

(1-2)

ROM + CO2

Alkanediazonium ions (R — N = N) were identified only after the introduction of superacid media and the stabilizing effect of electron-withdrawing substituents like fluorine was taken into account. The first such compound was the 2,2,2-trifluoroethanediazonium ion CF3CH2N^ , prepared by Mohrig and Keegstra (1967) by protonation of the corresponding diazoethane in FSO3H at -78°C. Alkene- and alkynediazonium salts (1.4 and 1.5) were characterized first in the 1950's (Newman and Kutner, 1951; Newman and Weinberg, 1956) and in 1985 (Helwig and Hanack), respectively. Today, compounds with diazonio groups attached to sp3-, sp2 (aromatic)-, sp2(alkene)- and sp-hybridized C-atoms are known. R

\

C=C

/N2+

R— C=C — N2+

X

X

R

R"

1.4

1.5

Alkane-, alkene-, and alkynediazonium ions are structurally and theoretically interesting compounds (Sects. 5.1 and 5.3), but they are of little interest for organic synthesis. An interesting development of diazo chemistry started in the 1960's because inorganic and coordination chemists became interested in diazo compounds with respect to four areas: 1) The well-known old laboratory preparation of dinitrogen by thermal decomposition of solutions containing the ammonium and nitrite ions had been thought for decades to involve nitrosation of ammonia, but it was only much later that Olah et al. (1985 a) found experimental evidence for the intermediacy of the parent diazonium ion HN^ (protonated dinitrogen): thanks to the development of superacid media, a number of other "simple" diazonium compounds of type XN2+ were found in the 1980's (see Sect. 3.1).

1.1 History of Aliphatic, Inorganic and Organometallic Diazo Compounds

3

2) Purely inorganic diazo compounds, which resemble aromatic diazonium ions, were discovered by the group of Muetterties (Knoth et al., 1964) in the context of their work on polyhedral boron hydrides. The l,10-bis(diazonio)octahydrodecaborate zwitterion was the first compound of that class (see formula 3.10 in Fig. 3.1). In the same year, but independently, Hawthorne and Olsen demonstrated that the parent of the bis (diazonio) compound mentioned above, the decahydrodecaborate diazonio ion, reacts with arenediazonium ions (see Zollinger, 1994, Sect. 12.11). This is the first azo coupling reaction of a purely inorganic coupling component. 3) and 4). It is a striking coincidence that two discoveries were made, also in 1964-65, by which diazo chemistry attained two firm positions in coordination chemistry: in 1964 King and Bisnett isolated and characterized the first transition metal complex containing an arenediazonium ion, a so-called aryldiazenido ligand (Sect. 10.1)*. Allen and Senoff (1965) found the first transition metal complex with dinitrogen as ligand. This discovery was not only very important for an understanding of the chemistry by which atmospheric nitrogen is taken up by living organisms (nitrogen fixation by nitrogenase), but it was soon demonstrated that the bonding of N2 to transition metals is in many, but not all, cases similar to the formation of organic diazo compounds (see Sects. 3.3 and 3.4). In contrast to aromatic diazo compounds, diazoalkanes are less important as large-scale industrial intermediates. Nevertheless, their dediazoniation reactions offer a series of important applications in organic synthesis, since Wolff (1902) discovered the rearrangement of diazo ketones into carboxylic acids (1-3). After R—CO—CHN2 + H2O

*-

R—CH2—COOH + N2

(1-3)

modifications, this reaction became three decades later the key to the Arndt-Eistert method for the preparation of homologous carboxylic acids (Arndt and Eistert, 1935, see Sect. 8.6). As a result of the introduction of stable precursors (see Sect. 2.4), diazomethane became available as an easy-to-handle reagent for the Arndt-Eistert reaction and for the alkylation of OH groups in alcohols, enols, and carboxylic acids. Since the 1950's and 1960's when (so-called) heteroatom organic compounds enjoyed increasing interest, the use of sulfonyl and phosphoryl diazo compounds for synthetic purposes became a frequent entry to S, P and other organic compounds substituted with less common groups. Reactions of diazocarbonyl compounds were in the cradle of what was much later named as 1,3-dipolar cycloadditions. After his pioneering work with diazoacetate (see above) Curtius suggested to his coworker Buchner to investigate reactions of this diazo compound and of diazoacetic acid with unsaturated carboxylic acids and carboxylates. Buchner (1888) investigated first the reaction of diazoacetate with fumaric acid - it was the first 1,3-dipolar cycloaddition, but at that time not realized as such.

* The first metal complex with an alkyldiazenido ligand was found three years later (Bagga et al., 1967), see Sect. 10.2.

4

/ Introduction

In the course of this work, Buchner found in 1889 a derivative of the hitherto unknown compound pyrazole by reaction of methyl diazoacetate with dimethyl ethynedicarboxylate (1-4). CH3OOC N

CH

9 C

N

COOCH3

I H

In spite of some related reactions discovered in the following 71 years, it was Rolf Huisgen who realized in 1960 that all these reactions were based on the addition of a 1,3-dipole to a dipolarophile (Scheme 1-5).

The structure of diazoalkanes is an example represented by these 1,3-dipoles:

There are numerous other 1,3-dipoles of the same type, from azides (-N 3 ) to ozone (O3). Huisgen (1963 a, 1984, p. 5) lists 18 examples, which lead to an enormous variety of heterocyclic and other compounds. Previously, these compounds were either unknown or difficult to obtain. No wonder that a book of two volumes (1623 pages) was published on 1,3-dipolar cycloadditions by Padwa in 1984! * This development is one of the most remarkable examples in organic chemistry that application of the principles of physical organic chemistry can lead to a complete and very diverse framework of synthetic methods. We agree with Padwa's statement that Huisgen's work in this area was monumental**. We will discuss 1,3-dipolar cycloadditions of diazoalkanes in Sections 6.2-6.4. Another relatively recent development is based on mechanistic interest in carbenes, for which the thermal and the photolytic dediazoniation of diazoalkanes has become one of the two major points of access (see Chapt. 8). * March (1992, p. 836) lists 27 books and review papers on that subject. ** A little personal episode may be mentioned here: In 1958 the present author visited one of the large German chemical enterprises. Its vice-president for research, just returned from a meeting in Munich, said: "I told Professor Huisgen that he should stop his research work on reaction mechanisms and that he should invent the Huisgen reaction". Two years later Huisgen had "his" reaction - thanks to his interest in reaction mechanisms! The combination of reaction mechanisms and novel synthetic methods is evident also in the title of Huisgen's autobiography (1994): "The Adventure Playground of Mechanisms and Novel Reactions".

1.2 Nomenclature and General References

5

Methylene (:CH2), the parent carbene, was already considered by Nef (1895, p. 359) to exist. Better evidence was found by Staudinger and Kupfer (1912) in the reaction of diazomethane with carbon monoxide, yielding ketene (1-6). CH2N2

-^^

:CH2

-^*

CH2=C=0

(1-6)

Staudinger's historical merits for our knowledge of diazoalkanes, based on his work between 1911 and 1921, became somewhat overshadowed by his later and clearly more fundamental and pioneering ideas about the formation and structure of macromolecules (Nobel Prize 1953). It should be emphasized, however, that his development of the concept of polymerization was, at least in part, based on his observations of the formation of polymethylene in the dediazoniation of diazomethane. Macromolecular chemistry, therefore, appears to be "a child of early diazo chemistry"! It is also appropriate to mention the modern mechanistic work on the very first type of reaction in the chemistry of aliphatic diazo compounds, namely deamination (1-1). In contrast to the 1,3-dipolar cycloadditions deaminations of aliphatic amines are relatively seldom applied for synthetic purposes (see Sect. 7.7), because they lead in most cases to a mixture of nucleophilic substitution products as well as elimination and rearrangement products. It has been clear, at least since the work of Young and Andrews (1944), Ingold's group (Brewster et al, 1950) and others, that, basically, these reactions belong to the class of nucleophilic aliphatic substitutions in spite of a bewildering number of complicating factors (see Chapt. 7). Returning to the mid-19th century and the discoveries of Piria and Griess the later development of their work is comparable to the case of two sisters who did not know that they were close relatives because they were separated at birth. They did not meet for decades. Few people in their neighborhood had the feeling that the two girls might be sisters. After many years some neighbors brought them together and the two girls realized that they had more in common than they realized during the long time of separation. They found out also that they even have cousins (inorganic and organometallic diazo compounds) that indeed showed similarities to one or both sisters. These characteristics were, however, hardly realized by the public before. From then on the sisters and cousins were happy and proud of their common decendency. This fairy-tale is a fancy background of Diazo Chemistry I and II!

1.2 Nomenclature and General References We emphasized in the Preface that the subject of this book and of that on aromatic diazo compounds (Zollinger, 1994) are closely related, but that the two books are independent. As a consequence, it should be possible to read one of the books without frequent consultation of the other. Strict adherence to that policy would force the

6

1 Introduction

author to repeat almost verbatim the section on nomenclature as given in the other book. We will not do that, but will provide a short summary of the present status of nomenclature rules for compounds and for reactions. We use the Nomenclature of Organic Chemistry of the International Union of Pure and Applied Chemistry, 1979 Edition ("Blue book'', IUPAC 1979), the Revised Nomenclature for Radicals, Ions, Radical Ions, and Related Species (IUPAC, 1993), the Guide to IUPAC Nomenclature of Organic Compounds (IUPAC, 1994 a), and additional rules applied by the Chemical Abstracts Service for the "1987-1991, Index Guide" (Chemical Abstracts, 1992). For quantities, units, and symbols in physical chemistry, we use the list published by IUPAC (1987 b). We are aware of the fact that readers, accustomed to units such as kcal or Hartree (instead of kJ), A (instead of pm or nm), etc., will have to think for a second before reading further, but we are convinced that books should be written for the younger generations who, one hopes, will grow up with a scientific language that will be identical around the globe and through all generations and fields of science. Therefore, we also prefer the system recommended by the IUPAC Commission on Physical Organic Chemistry for the nomenclature of reactions (IUPAC, 1981, 1989 a, 1989 b, 1989 c; see also Guthrie and Jencks, 1989) and already adopted in some modern textbooks (e. g. March, 1992). We use the term "diazo compounds" not only to name specific structures according to IUPAC rules (e. g., diazomethane, see below), but also as a class name (as meant in the title of this book and in chapter headings), including neutral, cationic, anionic, and radical compounds with the group — N2 or — N2 —, but excluding azo compounds, i.e., compounds in which the -N 2 - group is bound on both sides to C-atoms. Compounds RN^X~ are named by adding the suffix "-diazonium" to the name of the parent compound RH, the whole being followed by the name of X~ (Rule C-931.1). IUPAC (1979, 1994) gives in this context "benzenediazonium" as a specific example, but not methanediazonium. In the general literature, H3C —N^ and other aliphatic diazonium ions are, in most cases, called "methyldiazonium" and "alkyldiazonium" ions. As this usage is not consistent with IUPAC nomenclature, we recommend (and use in this book) the name methanediazonium etc. ion (salt) etc. Specific diazonium compounds are registered in Chemical Abstracts under the heading of the parent compound, e. g. Ct^N^BRjT under Methane, diazonium tetrafluoroborate. The substituent -N/ is called "diazonio" (not diazonium). The new Guide to Nomenclature (IUPAC, 1994a) includes a major change for naming diazo compounds of the general type R —N2 —X where R is an aliphatic, aromatic, or heterocyclic group, and X is any organic or inorganic group (Rule R-5.3.3.4). The rule is logically based on the fact that these compounds are derivatives of diazene (HN = NH). Particularly important for this book* is the nam-

* We were unable to use the 1994 names in volume I. The new IUPAC Guide became available six weeks before the manuscript of this volume was conveyed to the publisher!

1.2 Nomenclature and General References

7

ing of R —N2 —X, when R = alkyl, and X = OH or O~. These compounds were originally called diazohydroxides and diazotates (see Zollinger, 1994, p. 3, Table 1-1). More recently the names diazotic acid and diazoates were used, but now diazenols and diazenolates (both as (Z) and (E) isomers) are preferred. R is considered as a substituent of the parent molecule diazene. Therefore, the corresponding name has to be used, e. g., methyldiazenol, not methanediazenol. This may cause some confusion with the naming of the chemically related Lewis acid which, as mentioned above, is called methanediazonium ion! The logics, however, are clear: H3C —N^ is a derivative of the parent compound methane; in the case of H3C —N2 —OH, diazene is the parent. Compounds containing the neutral (formally zwitterionic) group =N2 attached to the C-atom are named by adding the prefix "diazo" to the name of the parent compound (Rule 931.4, e. g. diazomethane, ethyl diazoacetate). Unfortunately "diazo compounds" is not an entry in the General Subject Index of Chemical Abstracts. Diazomethane is found in the Chemical Substance index under "Methane, diazo-". The IUPAC rules for the nomenclature of chemical changes (see above) provide a general guideline of nomenclature for the so-called straightforward transformations. They include substitutions, additions, and eliminations that may involve configurational changes, but not molecular rearrangements. In contrast to "reactions", naming of "transformations" refers only to changes in the species designated as "substrate", but not to the changes in the reagent. Thus, "chlorination" is used for any process in which an atom or a group of a substrate is replaced by a Cl-atom, irrespective of the reagent used (C12, C1OH, Cl" etc.) and the mechanism (heterolytic or homolytic). The group or atom that is replaced can be specified in the complete name of the transformation, which comprises a) the name of the entering group, followed by a hyphen, b) the syllable *de' also followed by a hyphen, c) the name of the leaving group or atom, and d) the suffix -ation' (Rule 1.1). For example, the chlorination of acetic acid is a chloro-de-hydrogenation, the introduction of a chlorine atom by a Sandmeyer reaction is a chloro-de-diazoniation. Similar conventions are used for additions and eliminations. Additions include the attachment of two univalent groups or atoms to an unsaturated system, e. g. to alkenes, carbonyl groups, but also to one atom of the substrate as in carbenes (Rule 2.1). For example, the addition of hydrocyanic acid to the carbonyl group of an aldehyde is an O-hydro-C-cyano-addition. The addends are named in the Cahn-Ingold-Prelog order of priority (IUPAC, 1976). The rules for naming eliminations are analogous to those for additions, using the suffix -elimination'. The IUPAC recommendations for oral and written naming of organic reaction mechanisms (IUPAC 1989 a) are intended to replace the mechanistic nomenclature devised by Ingold (1953, 1969)*. Ingold developed his method in the 1930's, i. e. at a time when relatively few mechanisms were unambiguously known. In the following decades several new mechanisms and variants were established making the applica-

* A second system (IUPAC, 1989 b) allows a linear representation of reaction mechanisms for computer storage and retrieval.

8

/ Introduction

tion of that system quite complex and no longer self-explanatory. The IUPAC recommendations are more flexible and extendable to cases not known at present. These recommendations are based on indicating the steps of a mechanism by capital letter symbols (D for dissociation or detachment, A for association or attachment) for each step combined with plus signs. In concerted reactions, the symbols are given without a plus sign (AD). Capital letters are used to indicate bond formation or scission involving a nucleophile, an electrophile or a radical (AN, AE, AR; or DN, DE, DR, respectively). Table 1-1 gives some examples for classical mechanisms together with the corresponding notations of the Ingold system. The IUPAC document (1989 a, p. 47) includes a more detailed list. For chemists who are familiar with the old, but not (yet) with the new conventions, consultation of this list is recommended to denote a mechanism. In contrast to the Ingold system, the IUPAC recommendations allow description of more complex additions and eliminations, and mechanisms involving rearrangements and cyclizations. Table 1-1. Examples of notations for reaction mechanisms in the IUPAC system (1989 a) together with corresponding Ingold-system names. Ingold name

IUPAC name

Footnotes

Substitutions

SN2 SN1

ANDN D

N

+A

N

S N l'orB A L l

a)

SE2

b)

none

c)

DN + DE

El

d)

Rearrangement (intra-l/AN)l/DN + 2/AN(intra-2/DN)

none

e)

l/DN + 3/AN AE + DE

Addition AN + AE

Elimination

a) b)

c) d) e)

Nucleophilic substitution of 1-X-propene via an allyl cation, see Scheme (7-22) and text. SE2 was proposed by Ingold for the two-step electrophilic aromatic substitution. In analogy to his method for nucleophilic substitutions at a saturated C-atom, the corresponding one-step substitution at a saturated C-atom by an electrophile would also be an SE2 mechanism! A nonconcerted addition mechanism in which a nucleophile adds first followed by an electrophile in a separate step. A nonconcerted elimination analogous to c). Migration of a group in a nucleophilic aliphatic substitution, see Scheme (7-3 e) and text.

The mechanism of a nucleophilic substitution, in which cleavage of a nucleofuge Y from position 1 of an alkene leads to an allyl carbocation, is followed in a separate step by attachment of a nucleophile X in position 3 (1-7). The Ingold name SN1' (Table 1-1) indicates only that the mechanism could be related to the classical SN1

1.2 Nomenclature and General References

9

process. The IUPAC notation (1/DN + 3/AN), however, contains the additional information that the nucleofuge leaves from position 1 and that the nucleophile is introduced in position 3. V

/

V

/

(1-7)

x—c—

/

3

The last entry of Table 1-1 is detailed in (1-8): a two-step nucleophilic aliphatic substitution in which the loss of the leaving group Y is concerted with cyclization involving the group Z in position 2, the latter moving in the second step to the position 1, a process that is again concerted with addition of the nucleophilic reagent X.

f I

_C_C- Y

»

\ cA / -C

+Y-

+X

(1-8)

x—c—c—z 2

1

For terminology and concepts of physical organic chemistry, we mostly use the Glossary of Terms Used in Physical Organic Chemistry (IUPAC, 1994 b) and the Compendium of Chemical Terminology (IUPAC, 1987 a). The most comprehensive and recent overview on diazo compounds are the corresponding volumes of Patai's work The Chemistry of Functional Groups, namely the two volumes on diazonium and diazo groups (Patai, 1978), the two volumes on hydrazo, azo, and azoxy groups (Patai, 1975), and the two Supplement C volumes on triple-bonded groups (Patai and Rappoport, 1983). Volumes on diazo and diazonium groups (Patai, 1978) contain chapters on aromatic and aliphatic compounds. There are also chapters in which certain aspects of aromatic and aliphatic compounds are treated together. These volumes do not contain chapters on alkene-

10

1 Introduction

and inorganic diazonium ions. Organometallic compounds are discussed only briefly, as they have been investigated rarely before 1978. There is a chapter, however, on alkenediazonium salts in Supplement C (Bott, 1983). Detailed descriptions of preparative methods for diazoalkanes are provided by Houben-Weyl, Methoden der organischen Chemie: Volumes X/4 and E 14b (Mtiller, 1968; Klamann and Hagemann, 1990). In the 1980's, two monographs were published that cover parts of our book, namely Regitz and Maas' Diazo Compounds (1986) and Williams' Nitrosation (1988). The book of Regitz and Maas focuses on synthesis of aliphatic diazo compounds. It is disappointing, however, that very important areas of aliphatic diazo chemistry are neglected or, at best marginally or occasionally mentioned in that book, e. g., 1,3-dipolar cycloadditions, deaminations via diazo compounds, carbene and carbenoid reactions. Williams emphasized rather mechanistic and physical organic aspects. His book includes not only information on nitrosation of aromatic and aliphatic primary and secondary amines, but also on O-, S-, and C-nitrosation.

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

2.1 Stable Aliphatic Diazonium Ions All diazonium ions, whether aromatic or aliphatic, contain two nitrogen atoms in a manner similar to the two nitrogens in dinitrogen molecules. There is a triple bond between the two atoms, as can be concluded from NMR spectra and X-ray structure analysis (see Zollinger, 1994, Sect. 4.2). As dinitrogen is a very stable molecule, it is hardly surprising that the C-N bond is rather weak, and dediazoniation is a common reaction of diazonium ions. In solution at room temperature, an aromatic diazonium ion loses N2 in a first-order reaction with a half-life of some hours. Most salts of aromatic diazonium ions can be kept in the solid state almost indefinitely, if not heated or subjected to mechanical shock (see Zollinger, 1994, Sect. 2.3). Aliphatic diazonium ions, on the other hand, are extremely unstable. Although they were obtained as very unstable intermediates in 1848 when Piria treated aspartic acid (2-aminosuccinic acid) with nitrosating reagents, leading to malic acid (2-hydroxysuccinic acid), they were not identified directly for almost 120 years. Piria's reaction allowed, in some cases, the substitution of a primary amino group by a hydroxy group. This reaction is also characterized by eliminations and rearrangements (see Chapt. 7). Aliphatic diazonium ions were postulated and subsequently identified as intermediates in the acid-catalyzed decomposition of aliphatic diazo compounds (see Sect. 7.2). The reason for the quite different stability of aliphatic and aromatic diazonium ions is the strong n — n interaction of C(l) and N(a) in the aromatic series, which is, of course, not present in alkane diazonium ions (see Zollinger, 1994, Sects. 8.3 and 8.4). In the dediazoniation of an aliphatic diazonium ion (2.1), a primary product is a carbocation (2.2 in 2-1). The latter will either react with a nucleophile (solvent, anion from the mineral acid used for diazotization, etc.) or rearrange (see Sects. 7.3 and 7.4). ^+

products

(2-1)

R, R' = H, alkyl, aryl other substituents Diazo Chemistry II: Aliphatic, Inorganic and Organometattic Compounds. By Heinrich Zoliinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

12

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

The C — N bond of the transient diazonium ion may also be stabilized by elimination of a proton from the C(l) atom to form a diazoalkane (2.3). Although the diazonio group is a very strongly acidifying substituent, the deprotonation of the diazonium ion 2.1 is in most cases only competitive with the dediazoniation if the acidity of the C(a)-proton in 2.1 is further increased by additional acidifying substituents in either one or both groups R and R'. Such cases will be discussed in Section 4.3. Here we will concentrate on methods by which the diazonium ion 2.1 is stabilized to the extent that it can be observed and characterized in solution. This can be done by protonation of the diazoalkane at low temperature in super acids, i. e., in the absence of strong nucleophiles. The first alkanediazonium ion was obtained and characterized by Mohrig and Keegstra (1967). They prepared the 2,2,2-trifluoroethanediazonium ion (CF3CH2Nih) by protonation of the corresponding diazoethane in fluorosulfonic acid (FSO3H-CDC13) at -78°C. The ion was characterized by *H NMR spectroscopy. The spectra are consistent with protonation at C(a) (quartet at 6.3 ppm, /HF = 6.1 Hz) and not at N(P). At -20°C, dediazoniation took place, nucleophilic attack leading to the corresponding ester (CF3CH2 — OSO2F). Diderich (1972) described the protonation of l-phenyl-2,2,2-trifluorodiazoethane (C6H5-CN2-CF3) in FSO3H-SO2 at -60°C and the 1H NMR spectrum of the resulting ion. The quartet at 5.6 ppm with /HF = 6 Hz can be ascribed to the added proton in the diazonium ion C6H5CH(N2+)CF3. In analogous fashion, Mohrig et al. (1974) prepared the bis (trifluoromethyl)methanediazonium ion [(CF3)2CHNih] by protonation of bis (trifluoromethyl)diazomethane [(CF3)2CN2] in FSO3H-CDC13 at -70°C. A kinetic study of the stability of this diazonium ion was carried out using *H NMR spectroscopy. The energy of activation for dediazoniation was found to be Ea = 79 ± 9 kJ mol"1. The parent compound, methanediazonium ion (2.4, Scheme 2-2), was first identified in solution by Berner and McGarrity (1979) in an investigation of protoncoupled 13C NMR spectra of the system CH2N2-FSO3H-SO2C1F in the range — 85 to —106 °C. TWo major peaks were observed, one of which was a quartet at 43.78 ppm. On heating, dediazoniation took place and methylfluorosulfate (H3C-OSO2F) was detected. With FSO3D, the decoupled 13C NMR spectrum changed in the expected manner (singlet to triplet) and the methylfluorosulfate product was found to be also monodeuterated. The second product was originally assumed to be the isomeric methylenediazenium ion H2C = N + = NH, i.e., N(/?)-protonation was proposed to have taken place. McGarrity and Cox (1983) subsequently found that this second product is only formed because the system originally investigated contained some SO2. Methylenediazenium ion cannot be detected in FSO3H - SO2C1F, but only in a more acidic medium, i.e., in SbF5 —FSO3H (2.5, Scheme 2-2). Methylenediazenium ion is thermodynamically less stable than methanediazonium ion; its formation is a kinetically controlled process. McGarrity's results are the best evidence for the ambident nucleophilicity of diazomethane: both, the C- and the N(/?)-atoms are nucleophilic centers/This ambivalence was substantiated much earlier, however, by Huisgen and Koch (1954,

2.1 Stable Aliphatic Diazonium Ions H2C-N2H I

13

2.6

(2-2) -SO

CH2N2 + HOSO2F

-120°C

-120°C < > -120°C

+ CH2N2H + FSO3~

SbFn —^

. CHoNoH

25

T

'

CH3N2+ + FS03'SbF5

^

CH2N2 + HOSO2F-SbF5

SbF5 CH3OS02F + N2

<

*

CH3OS02F.SbF5 + N2

1955), who demonstrated that diazomethane reacts at both these centers with arenediazonium salts (see Sects. 4.4 and 6.5, and Zollinger, 1994, p. 339). Scheme 2-2 summarizes the results of the work of McGarrity and Cox. The scheme also includes the reaction with SO2: Methylenediazenium ion (2.5) adds SO2 at the C-atom and forms compound 2.6. Such complexation of strong alkylating agents by SO2 has been well documented by Gillespie et al. (1976), Peterson et al. (1976), and by Olah and Donovan (1978). More recently, Olah (1993) postulated that the equilibrium between the methanediazonium ion (2.4) and the methylenediazenium ion (2.5) in superacid media is not a deprotonation-reprotonation process via diazomethane as shown in (2-2), but involves the diprotonated dication (H3C-^=I^-H). So far, however, there is no experimental evidence nor a theoretical basis available for this dication. It is interesting and unexpected that diazoethane reacts in a different way under similar conditions (2-3) (McGarrity et al., 1980). In FSO3H-SbF5-FSO2C1, only ethyl fluorosulfate (2.8) and the 7V-protonated diazenium ion (2.9) are observed; the C-protonated diazonium ion (2.7) is not detected. Attempts to protonate diazocarbonyl compounds in superacids at C(l) failed (Allard et al., 1969; Wentrup and Dahn, 1970). When diazoacetone (2.10) was treated at -60 to -80°C in FSO3H - SbF5 - SO2 or in HF-SbF5-SO2, the Oprotonated enoldiazonium ions with (Z)- and (^-configuration (2.11 and 2.12) were detected by *H NMR spectroscopy. It may be that there is a hydrogen bond formed between the OH and the diazonio group in 2.11. At temperatures above — 60 °C, the C-protonated ketodiazonium ion 2.13 is formed preferentially. N2 is eliminated rapidly and the resulting carbenium ion adds to FSO3~ forming a fluorosulfonate (Wentrup and Dahn, 1970). Two years before Wentrup and Dahn's work Avaro et al. (1968) investigated two other a-diazo ketones in FSO3H-CDC13-SO2. They found that 2-diazo-5a cholestanone (2.14, R=H) and its 4,4-dimethyl derivative (2.14, R=CH 3 ) exhibit a

14

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds CH 3 —CH = N2 + FSO3H -120°C

[CH3— CH2-N = N FS03-]

CH3-CH = N=

2.9

2.7 -60°C

-N,

CH3—CH2—OSO2F

(2-3)

CH3—CH —N=NH

2.8

OSO2F -N2 +H2O

CH3—CH=O + FSO3H

R

/H

x

R

x

"

N2

"

2.10 HF-SbF5-SO2 or FSO3H-SbF5-SO2

<-60 Q C

>-60°C

(2-4)

\

^=0 HO

2.11

/H NJJ+

R

\

+

A+

C=C

HO

H

2.12

98^17

R

\

C—C O^

2.13

2.2 Introduction to the Methods for the Synthesis of Aliphatic Diazo Compounds

15

new *H NMR signal. The authors ascribed this signal to the corresponding 2-diazonio-2-hydro derivatives. This result is rather surprising as H/D exchange of diazo ketones in acidic D2O indicates reversible C-protonation. The explanation may be that the 2-hydroxyalkenediazonium ions 2.11 and 2.12 are thermodynamically much more stable than the alkanediazonium ion 2.13 (see also Sect. 2.10). An important contribution to this question was made recently in a joint investigation by Laali and Maas (Laali et al., 1993). Diazoacetates containing a tri(2-propyl)silyl- [(2-C3H7)3Si-] or a pentamethyldisilanyl group [(CH3)3Si - (CH3)2Si-] were found to be more stable in superacid media than diazoacetates without silyl groups. The (Z)- and (£T)-O-protonated alkenediazonium ions could be identified in FSO3H-SbF5 (1:1)-SO2 at <-75°C and O-protonated alkanediazonium dications were found in FSO3H-SO2. The methanediazonium ion has been generated in an ion cyclotron and its gasphase reactions have been studied (Foster and Beauchamp, 1972; Foster et al., 1974; McMahon et al., 1988)*. Complexes of alkanediazonium ions with transition metals (Mo and W) are stable in the solid state (Lappert and Poland, 1969; Day et al., 1975; Herrmann, 1975a; Herrmann et al., 1975b; Hillhouse et al., 1979; see discussion in Sect. 10.3). Foster and Beauchamp found that the decomposition of the methanediazonium ion to a methyl cation and dinitrogen in the gas phase is endothermic to the extent of 158 kJ mol"1. This is indeed in dramatic contrast to its very rapid dediazoniation in solution. Obviously, this is due to nucleophilic participation of the solvent at the C-atom from the back side relative to the diazonio group. In aromatic diazonium ions this pathway cannot be considered for steric reasons. This assumption was already postulated by Bartlett and Knox in 1939. Curtin et al. (1962) were able to trap an alicyclic bridgehead diazonium ion in solution for the first time in 1962 (see Sect. 6.1).

2.2 Introduction to the Methods for the Synthesis of Aliphatic Diazo Compounds The preparation of aromatic and heteroaromatic diazonium compounds follows, with very few exceptions, the same basic pattern, namely the diazotization of the corresponding amines. Under appropriate conditions (temperature and acidity), formation of the desired diazonium ion is a rapid and smooth process with a yield of almost 100%. Diazotization may even be applied as a titration method (see Zollinger, 1994, Sect. 2.1). * Formation of the gaseous methanediazonium ion by the fragmentation of the azomethane molecular ion (Prasil+and Forst, 1968) and by the nucleophilic displacement of HF in protonated fluoromethane (CH3FH) by N2 (Holtz et al., 1970) has also been reported.

16

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

The situation is completely different for the synthesis of diazoalkanes including their derivatives y)C = N2. Here, more than ten different types of reactions are available. The choice between these types is, roughly speaking, not dependent on the structure of the substituents X and Y. For several specific aliphatic diazo compounds, more than one of these reaction types was, and still is, recommended. Small changes in the structure frequently have great influence on the yield: several examples will be given in the following sections. For the organic chemist who wants to obtain a specific aliphatic diazo compound as a synthetic reagent, we strongly recommend to search the literature for a welldescribed synthesis of that specific diazo compound, not to study the general literature on aliphatic diazo compounds and to adopt a good method described for a slightly different compound. At present, with the relatively easy online access * to the chemical literature, this information can be found rapidly. An even faster and cheaper, and, for some years, also better information source, are the 267 pages of the Compound Index in Vol. E14b II of Houben-Weyl (Klamann and Hagemann, 1990). Aliphatic diazo compounds are often formed as short-lived intermediates in the synthesis of other compounds, e.g., of carbenes and carbenium ions, which are themselves transient intermediates for other products. In such cases, starting materials and methods are very often basically the same as for synthesis of diazo compounds as final products, but performed at higher temperature under irradiation or in other solvents. Such reactions will not be discussed here but in Chapter 7, which deals with dediazoniations of aliphatic diazo compounds. Another important criterion is the availability of the starting material. Table 2-1 shows ten types of synthetic process. Methods 7 and 2 are based on aliphatic amines, 5-5 on derivatives of carbonyl compounds, 6 on hydrocarbons with a relatively acidic CH proton, and 7-9 are reactions of diazoalkanes obtained by one of the types 1-6. Reaction 10 involves a diazo ketone, which can be obtained by reaction 9, the first step of the Arndt-Eistert synthesis. The first method corresponds essentially to aromatic diazotization. As discussed in Section 2.1 (Scheme 2-1), this method is applicable for the synthesis of a diazo compound only if loss of a proton from the C(a)-atom of the primarily formed alkanediazonium ion is faster than the loss of dinitrogen. Method 2 is related to the first method, as the starting material, the 7V-nitroso amine, is also obtained by the nitrosation of a compound containing an NH group. In this case R refers not only to an alkyl group, but also to various other groups (see Sect. 2.4). In addition, 7V-alkyl,7V-nitroso sulfonamides can be used in an analogous way as carboxamides in method 2. Methods 3-5 are considered if the corresponding carbonyl compounds are available for the synthesis of the oximes, hydrazones, or 4-toluenesulfonyl-hydrazones. As discussed in Section 2.5, reaction type 5 can also be applied to obtain adiazo ketones, starting from a ketone in which a CH2 group adjacent to the carbonyl group is oximated. I emphasize "relatively" for similar reasons to those mentioned recently by an expert (Zass, 1994).

2.2 Introduction to the Methods for the Synthesis of Aliphatic Diazo Compounds

17

Table 2-1. Types of diazoalkane syntheses. Orgflrac Syntheses a)

General scheme of the syntheses

No.

H 1 — C-NH2 + HN02

-**

^C=N2 + 2H2O

2

(2)

H O 1 II — C— N-C— R + OH~ 11 1 NO

-^

^C=N2 + H2O + RCOO~

4

(3)

^C=N-NH2 + Oxb)

-^

^C=N2 + H2O + Red

4

(4)

^C=N— NHSO2Arc) + OH"

^^

^C^N2 + H2O + ArSO2~

1

(5)

^X=N-OH + NH2C1

-*

^C=N2 + H2O + HC1

1

-^

^C=N2 + ArSO2NH~

3

-^

?H xN2 ~ C ~~ C \

(1)

H (6)

(7)

— C~ d > + N3S02Arc)

C=O + J^C=N2

H

(*)

^C=CC^ + ^C=N2

(9)

RCOC1 +

«»,

"^C=^N22 R-C' + OH~ II 0

H

^C=N2

1

2

c2

^ ~h" \

N

°

-^

R— C 1I I1 0

+ HC1

2

-*>

^C=N2 + ROXT H

1

a

) Number of syntheses described in detail in Organic Syntheses, Coll. Vol. I- VIII (1932-1994) and Vol. 70-71 (1992-1993). b ) Ox = metal oxides and various other oxidants for hydrazone oxidation. c ) Ar = 4-CH3C6H4 in most cases. d ) Or a precursor of a carbanion.

The diazo transfer method 6 is also used for aromatic diazonium salts (see Zollinger, 1994, Sect. 2.6). Diazo transfer is, however, more relevant for the synthesis of aliphatic diazo compounds. In addition to the schematic presentation in Table 2-1, the transfer of N2 from the azide to the carbanion may be combined with the dissociation of certain groups attached to the anionic carbon (see Sects. 2.6 and 2.7). The last four reaction types are characterized as being basically either additions (7-9) to or cleavage 10 of an aliphatic diazo compound containg the corresponding

18

2 Methods for the Preparation of Alkam, Alkene, and Alkyne Diazo Compounds

structural requirements. There are other related addition reactions that are used, particularly for the introduction of heteroatom groups into diazoalkanes. Table 2-1 contains the number of specific examples of the various reaction types that can be found in Organic Syntheses up to 1994. Examination of the more recent volumes of Organic Syntheses is also recommended because, in most cases, they provide information on the acute and chronic toxicity and other dangerous properties (tendency to explode, etc.). Toxicity and tendency to explode are indeed serious hazards to be taken into account when synthesizing and working with aliphatic diazo compounds. It is astonishing that most monographs on diazo compounds do not discuss or even mention these problems. Based in part on work published by Staudinger and Gaule (1916), Eistert et al. (1968, Table 1, p. 486) classify diazoalkanes in the following sequence of increasing thermal stability, i.e., decreasing tendency to explode: R2CN2 < ArCRN2 < Ar2CN2 < (RCO)2CN2 « (ArCO)2CN2 R = H or alkyl Primary diazoalkanes, i. e., monosubstituted diazomethanes, are more stable than the corresponding secondary (disubstituted) diazoalkanes. In the series of primary diazoalkanes, the tendency for decomposition increases from diazomethane to 1-diazooctane (Adamson and Kenner, 1935). The remarkable stability of silylated diazoalkanes (Seyferth et al., 1968, 1972; Seyferth and Flood, 1971) has led to investigations on their use in synthesis as a stable and safe substitute for diazomethane (Aoyama and Shioiri, 1981; Mori et al., 1982; Shioiri et al., 1990; Anderson and Anderson, 1991, see Sect. 2.6). (Trimethylsilyl)diazomethane is now commercially available (Petrarch). At least one explosion of diazomethane has been observed at the moment crystals suddenly separated from a supersaturated solution. Stirring with a Teflon-coated, i. e., relatively soft, magnetic stirrer is greatly preferred to a ceramic or glass stirrer or to swirling the reaction mixture by hand. As diazoalkanes also undergo dediazoniation by photolysis (Sect. 8.1), solutions of these compounds should not be exposed to direct sunlight or placed near a strong artificial light source. Most diazomethane explosions occur during distillation from an ether solution. Under no circumstances should all the ether be distilled from the reaction vessel: an excess must always be present. Sharp glass edges facilitate the explosive decomposition of diazomethane, so the ends of glass tubes should be rounded in a flame and ground-glass joints should be replaced by cork or rubber. Particular caution should be taken when a solvent with a higher boiling point then ether is used. Such a solvent has a lower vapor pressure than ether so that the concentration of diazomethane in the vapor phase above the reaction mixture is higher and an explosion is more likely to occur. Further useful information on precautions to be taken when synthesizing or working with diazomethane are given in the Organic Synthesis contributions of De Boer and Backer (1963), Moore and Reed (1973), Black (1983) and by Cohen in the Journal of Chromatography (1984).

2.2 Introduction to the Methods for the Synthesis of Aliphatic Diazo Compounds

19

Toxicity of diazoalkanes is a particular problem because of their high volatility. The first members of the homologous series of unsubstituted diazoalkanes are gases at room temperature. Boiling points are as follows: CH2N2: — 24 to — 23°C (101.3 kPa = 760 Torr, Staudinger and Kupfer, 1912); CH3CHN2: -19 to -17°C (11.9 kPa, Adamson and Kenner, 1937, also b.p.'s of following diazoalkanes): CH3CH2CHN2: -8.0 to -7.5°C (5.53 kPa); (CH3)2CN2: -31 °C (1.87 kPa); CH3CH2CH2CHN2: -5.5 to -3.5°C (3.4 kPa); (CH3)2CHCHN2: -1 to +1°C (1.26 kPa). Higher homologs (up to 1-diazooctane) were obtained only by co-distillation with ether; their boiling points are therefore not known (Adamson and Kenner, 1935, 1937). Di(tert-butyl)diazomethane is described by Barton et al. (1974) as an orange liquid that can be distilled at room temperature in vacuo. Diazomethane freezes at -145°C (Aldrich, 1989). The main danger of diazoalkanes is that one can work with them for some time without noticeable effects, but later asthma-like symptoms develop, followed by an allergic oversensitivity. Toxicity of diazoalkanes is due to their acid-catalyzed decomposition to form carbocations. These ions alkylate desoxynucleic acids. This alkylation is the cause for the carcinogenicity of the 7V-nitrosodi- and -monoalkylamines, which is discussed in more detail in the context of the chemistry of nitroso amines (Sect. 4.2). The Nnitroso derivatives of primary amines are precursors of the aromatic and aliphatic diazonium ions. As shown in Section 5.6 7V-nitroso compounds of secondary aliphatic amines undergo enzymatic reactions in living organisms in which carbocations are ultimately formed. Therefore, method 2 for diazoalkane syntheses in Table 2-1 is, in principle, questionable, because the 7V-nitroso compounds required are toxic. Therefore, the synthesis of diazomethane starting with 7V-nitroso methylurea (see Sect. 2.4) had to be abandoned, although it was a popular access to diazomethane for many years. This nitroso compound has been reported to be a potent carcinogen (Graffi and Hoffmann, 1966). A large number of syntheses of aliphatic diazo compounds (including all the methods summarized in Table 2-1) have been discussed by Eistert et al. (1968), by Regitz (1972, 1974, 1977 a, 1977 b, 1978), Hegarty (1978), Regitz and Heydt (1984), Regitz and Maas (1986) and in a volume of Houben-Weyl (Bohshar et al., 1990). In the books of Regitz (1977 a, 1977 b) and of Regitz and Maas (1986) and in HoubenWeyl, many examples can be found compiled in tables together with the corresponding yields. Careful scrutiny of these tables is particularly recommended in the context of the remarks made above. We will not repeat the tables and summaries published in the monographs mentioned above in the following sections on syntheses of diazo compounds. Some miscellaneous methods, which do not belong to the types of syntheses in Table 2-1, are known, but have no significance. They have been discussed by Regitz and Maas (1986). The extremely large variety of methods available today for the synthesis of diazoalkanes and their derivatives in the widest sense is most evident by examination of the 410 pages on diazo compounds in the corresponding new volume of HoubenWeyl (Klamann and Hagemann, 1990) or even by simply browsing through the table of contents. There, the methods are systematized in more than 300 sections, built up

20

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

with a seven-digit decimal classification! It cannot be the aim of the present book to list all those methods. For the same reason, Chapter 2 includes little information on the synthesis of diazoalkanes containing a heteroatom group at the diazocarbon atom (e.g., 1-diazo-l-S-alkanes with S = - S - , -SO-, -SO2-, l-diazo-7V-alkanes and 1-diazo-l-P-alkanes), because the preparations of these diazoalkanes would have to be treated in several sections of this chapter besides some specific syntheses. Bohshar et al. (1990) have already discussed them comprehensively (1-S-derivatives: p. 1292, l-N: p. 1307, 1-P: p. 1316).

2.3 Preparation of Aliphatic Diazo Compounds by Nitrosation of Aliphatic Amines As already indicated in the preceeding section, nitrosation of aliphatic amines yields alkanediazonium ions with a considerable life-time only in superacids and at very low temperature. Under more usual conditions, the diazonium ion either loses N2 and the carbocation formed yields solvolysis products (in water the corresponding alcohol) and various rearrangement products or, alternatively, a proton is eliminated from the C(a)-atom to give a diazoalkane (2.3 in Scheme 2-1). In this manner, Curtius (1883) prepared the first aliphatic diazo compound, diazoacetic ester (see Sect. 1.1), from aminoacetic ester (glycine ethyl ester). His original procedure consisted of dissolving the glycine ethyl ester (or its hydrochloride) in water and adding sodium nitrite, sulfuric acid, and ether. The diazo compound formed dissolves on shaking in the ether layer, which is then separated, dried, and purified. Ethyl diazoacetate, N2 = CH —COOC2H5, is formed in good yield (80-94%). It can be distilled without danger under reduced pressure or in steam. Apart from Curtius's revised procedure (1888a), there are several examples of examined preparation methods in the literature (see Womack and Nelson, 1955, and Searle, 1963). Because of the required loss of a proton, the applicability of this method is restricted to those amines that carry strongly electron-withdrawing substituents, such as COOR, CONR2, CN, CH3, a,a'-diketo groups or phosphoryl groups, on the neighboring C-atom or on the carbon atoms on both sides. Dehmlow et al. (1986) were able to show that 2-aminoazulene derivative 2.15 can be diazotized in aqueous dioxane with NaNO2 and sulfuric acid (2-5). The diazo compound is formed under deprotonation at the methylene group in position 6*.

* Aminoazulenes without an activated methylene substituent (such as 2.15) undergo nitrosations in the same way as benzenoid aromatic amines, see Zollinger, 1994, p. 28.

2.3 Preparation of Aliphatic Diazo Compounds by Nitrosation of Aliphatic Amines

21

COOC2H5

(2-5) COOC2H5

2.15

HNOo

(2-6)

2.16

As the proton release is often too slow under the acidic conditions used for the diazotization of aromatic amines, syntheses of aliphatic diazo compounds by this method are carried out without an excess of mineral acid. Usually, equimolar amounts of amine, HC1 and NaNO2, or amine and NOC1, are used. A better alternative is nitrosation with pentyl nitrite in the presence of up to 30% acetic acid, as found by Takamura et al. (1975). Yields higher than 60% were obtained with aamino-substituted esters of some aliphatic carboxylic acids. The diazo compound is often extracted into an immiscible organic solvent as soon as it is formed. Searle (1963) recommends dichloromethane for the synthesis of diazoacetates, as CH2C12 has the ability to protect the diazo compound from decomposition caused by aqueous mineral acid. Another synthesis of an aliphatic diazo compound in a two-phase system was reported by Moore and Arnold (1983). 4-Diazo-5-alkynyl-7V-hexyl-5-methoxy pyrrolidine-2,3-diones (2.17) were synthesized by nitrosation of the corresponding 3-chloro-4-amino-5-alkynyl-5-methoxy-A/r-n-hexyl-3,4-pyrrolidenine-2-ones (2.16) in a mixture of dichloromethane and aqueous HC1 at 0 °C (2-6). The overall reaction is probably a diazotization followed by a hydroxy-de-chlorination and a hydroxyde-protonation. It is even possible to nitrosate an aliphatic amine in a basic medium if nitrosyl chloride is used as reagent (Miiller and Rundel, 1958; Miiller et al., 1960a)*. A solu* Metal-nitrosyl complexes can also be used for diazotizations at relatively high basicities, as discussed later in this section.

22

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

tion of NOC1 in anhydrous ether is added slowly to a three- to four-fold excess of methylamine (2-7) at -80°C. The methylammonium chloride precipitate formed is filtered off, and an aqueous solution of 40% KOH (cooled to -20°C) is added to the filtrate. The diazomethane (2.20) formed is dissolved in the ether layer, which can be used as such for methylation. It can be shown by UV spectroscopy that the primary product is 7V-nitrosomethylamine (2.18). Addition of potassium ethoxide instead of aqueous KOH permits isolation of potassium (Z)-methyldiazenolate (2.19); the latter is very stable and can be transformed into diazomethane by treatment with aqueous KOH (2.7). The (Z)-configuration of the methyldiazenolate 2.19 was confirmed by X-ray analysis (Huber et al., 1965). Although this method has already been patented (Phrix-Werke, 1960, 1962), it is not widely used. x~

C2hLOK

—^

/

^

- C2H5OH

K+

N

H3C —N

2.19 NOCI-ether, -80°C H3C —NH2

+•

H3C —NH—NO

K

2.18

KOH-H2 2O

—^

H2C = N2

2.20

Bakke and Svendson (1981; see also Bakke, 1982) investigated whether the yield of diazo compounds in reactions of an excess of the corresponding amine with NOCI in ether at low temperature (-50 to -75 °C) could be improved by varying the procedure used for work-up of the crude reaction mixture. Their results are disappointing with respect to the yields and the number of by-products. For example, the best yield of phenyldiazomethane from benzylamine among five work-up procedures was 31%; four other products were identified (with other procedures up to nine by-products were detected). With 1-aminooctane, the same method led to a 40% yield of 1-diazooctane, but no diazo compound with 2-aminooctane! Even in series of nitrosations of alkylamines with electron-withdrawing substituents, such discrepancies between comparable compounds are known. Thus, Oilman and Jones (1943) found 10% of l-diazo-2,2,2-trifluoroethane in the reaction of 2,2,2-trifluoroethylamine, HC1, and NaNO2. This result was confirmed by Dyatkin and Mochalina (1964). Nevertheless, Atherton et al. (1971) were unable to synthesize l-diazo-2,2-difluoroethane by nitrosation of 2,2-difluoroethylamine and with 2,2,3,3-tetrafluoropropylamine they obtained a yield of only 10%. Good yields are reported, however, for the diazotization of the fluorinated aminoalkane 2.21 (Coe et al., 1983) and of 2-amino-l,l,l-trifluoro-3-nitro-propane (2.22, Aizikovich and Bazyl, 1987). Jin et al. (1992) claim that l-diazo-2,2,2-trifluoroethane can be ob-

2.3 Preparation of Aliphatic Diazo Compounds by Nitrosation of Aliphatic Amines

F3C-CF2

CH2—NH2 C

FgC-CF/

23

^ O2N—CH2—CH—CF3

X

CF3

2.21

2.22

tained better and more safely by a modified Bamford-Stevens reaction (see Sect. 2.5). The first diazocarbonyl compound reported (Curtius, 1883, see Sect. 1.1) was the nitrosation product of glycine ethyl ester (2.23, n = 0). Later, Curtius (1904), Curtius and Darapsky (1906), and Curtius and Thompson (1906) synthesized the diazo derivatives of the corresponding di-, tri- and tetrapeptide esters (2.23, n = 1,2,3). M2=CH—CO— (NH—CH2—CO)n— OC2H5 2.23

Given the problems in obtaining acceptable yields in nitrosation of aliphatic amines, it is clear that such difficulties are expected to multiply enormously, if only one of two amino groups should be nitrosated. Selective nitrosation (2-8) of one of two aliphatic amino groups was investigated for the synthesis of azaserine (O-diazoacetyl-L-serine; 2.25) by Moore et al. (1954) and Nicolaides et al. (1954). Azaserine is a natural diazoacetate, isolated by Fusari et al. (1954 a, 1954 b) from culture broth filtrates of a Streptomyces strain. The original synthesis had to be performed within the pH range 4.5-5.0 in order to nitrosate predominantly the amino group of the glycine residue. Even so, the yield of azaserine was less than 6%, when the procedure was reproduced by Curphey and Daniel (1978). O H2N — CH2—C — OCH2—CH—COOT

N2=CH—C — OCH2— CH—COO+

2.24

(2-8)

NH3

2.25

A resurgence of interest in azaserine as a cytotoxic amino acid for use against tumors of the exocrine pancreas in the 70's (see review by Longnecker, 1984) prompted re-examination of the synthesis of azaserine. The low yields obtained in the original synthesis are due to competing reaction of the serine amino group in Oglycylserine (2.24). Therefore, Curphey and Daniel (1978) protected this group as the trifluoroacetylamino derivative (2.26). In this way the amino group of the glycyl residue was smoothly converted to the diazoalkane by nitrosation (2-9) with aqueous

24

2 Methods for the Preparation of Alkane, Athene, and Alkyne Diazo Compounds

O II H3N—CH2—C—OCH2—CH—COCT NHCOCF3

2.26

LiN02, CICH2COOH

O N2=CH—C—OCH2—CH—COOH

(2-9)

NHCOCF3 Acylase I

O II N2=CH—C—OCH2—CH—COO+

NH3

2.25

lithium nitrite and in the presence of a catalytic amount of chloroacetic acid *. The trifluoroacetyl protecting group at the serine amino group was finally removed enzymatically with acylase I. The overall yield of this process is reported to be 49%. The structure derived by Fitzgerald and Jensen (1978) indicates that, relative to other diazoalkanes with a carbonyl group in the a-position, azaserine is relatively little influenced by conjugative effects (zwitterionic mesomeric structure of a diazonium enolate, see 2.31 a-c below, and Sect. 5.2). a-Aminoacetamides can be converted into the corresponding diazoacetamides, generally with low to moderate yield. An exception is the formation (2-10) of the benzhydryl ester of 6-diazopenicillic acid (2.28) which is obtained in >90% yield by neutral nitrosation of the corresponding amine 2.27 with NaNO2 in aqueous acetone (Matlin and Chan, 1981). In a-aminoacetohydrazide (2.29), the amino group and the N(/?)-atom of the hydrazino group will be nitrosated (2-11). The result is diazoacetyl azide (2.30) which is, surprisingly enough, claimed to be stable in spite of the cumulation of two potentially explosive substituents (Neunhoeffer et al., 1968). The yield, however, is only 10-15%.

* Curphey and Daniel (1978) found the catalytic effect of this acid by serendipity. They observed that crude samples of 2.26 reacted with aqueous LiNO2 much more rapidly than the recrystallized samples. TLC tests indicated 7V-(trifluoroacetyl)serine as a likely catalytic impurity, and chloroacetic acid was selected as an acid of similar strength. Neither acetic nor hydrochloric acid was as effective. The authors chose LiNO2 rather than NaNO2, because inorganic Li salts are soluble in the ethanol used for purification of azaserine (Curphey, 1989).

2.3 Preparation of Aliphatic Diazo Compounds by Nitrosation of Aliphatic Amines H

25

N2

H NaN02/H2O/(H3C)2CO

H

^

'""""

COO—CH2—C6H5

H

2.27

x

( " )

COO—CH2—C6H5

2.28

2/HCI CH 2 CI 2 /H 2 O,-5 9 C / H2N—NH

*

*

/ N3

2.29

C-CH=N2 *

(2-11) '

v

2.30

The nitrosation method is not recommended for a-aminoketones, but it works well for 2-amino-l,3-dicarbonyl compounds, as found by Wolff (1902)* for the preparation of 3-diazopentane-2,4-dione (2.31). Cyclic diazo-a,a'-diketones, such as 2-diazocyclohexane-l,3-dione (2.32, R=H) and its 5,5-dimethyl derivative (diazodimedone, 2.32 R=CH 3 ), can be synthesized without major difficulties (Eistert et al., 1959; Stetter and Kiehs, 1965). The parent compound, diazomalonodialdehyde (2.33) was prepared only in 1973 by Arnold and Sanliova. The smooth formation of diazo-a,a'-diketones and the decreased tendency for proton addition at the central C-atom can be explained by the resonance structures 2.31 a-c. l,4-Bis(diazo)cyclohexane-2,3,5,6-tetraone (2.34) is a borderline case between adiazo ketones and (aromatic) 1,4-quinone diazides. Compound 2.34 can be obtained by bis-diazotization of l,4-diamino-benzene-2,3,5,6-tetrol (Henle, 1906). //

O

P //

H3C — C

H3C

C

H3C —C

H3C —C

H3C—C

O~

O 2.31 a

O

2.31 b

.0

//° N2

2.31 c

Qv

p

°

°

C=N2

xX

o

2.32

or / H3C—C

2.33

2.34

* In that paper, Wolff assigned, however, the wrong structure to the product, but corrected it later (1912) himself.

26

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

Acylated or sulfonated a-amino ketones are smoothly converted to the corresponding a-diazoketones. Open-chain diazo-a,a'-dicarbonyl compounds form complexes with boron trifluoride. There are two types of such complexes, as shown by Fahr and Hormann (1965) by means of IR spectra. In the solid state, the complexes show similarities to aromatic diazonium compounds, they have a quasi-aromatic six-membered chelate ring (2.35). They also undergo a reaction typical of solid aromatic diazonium salts, namely the Balz-Schiemann reaction (see Zollinger, 1994, Sect. 10.4), in which the corresponding fluoro-a,a'-dicarbonyl compound 2.36 is formed (2-12) (Prim and Schank, 1978). In benzene solution, however, the 1:2 complex is not chelated, rather Fahr and Hormann's IR data indicate structure 2.37.

(and enols)

= C6H5>C2H5>CH3 R'= C6H5JCH3,OCH3,OC2H5

(2-12)

2.37

a-Phosphorylalkylamines can be transformed into phosphoryldiazoalkanes by nitrosation. The phosphoryl group is, however, a weaker electron-withdrawing group than the carbonyl group. Therefore, nitrosation should be conducted in acetic acid and not in mineral acid (Regitz and Eckes, 1980). The first phosphoryldiazoalkane synthesized was (diazomethyl)diphenylphosphine oxide (2.38) (Kreutzkamp et al., 1965). C6H5 O=P —CH=N2

2.38

C6H5

An interesting substituted diazomethane, diazomethanedisulfonic acid (2.39), was mentioned by von Pechmann in 1895, as being obtained by the reaction sequence (2-13). So far as we know, this compound has not been investigated further during

2.3 Preparation of Aliphatic Diazo Compounds by Nitrosation of Aliphatic Amines

HCN + 2 NaHSO3

*• (NaO3S)2CHNH2

HN 2

° > (HO3S)2C=N2

27

(2-13)

2.39

almost 100 years! As compounds with two sulfonic groups at the same C-atom are difficult to obtain, it seems questionable whether von Pechmann really obtained the compound 2.39. The diazotization products of 2- and 4-aminophenols, -naphthols (etc.), possess a mesomeric (zwitterionic) phenolate-diazonium and quinone-diazide structure. We discussed these structures in the context of aromatic diazotization (Zollinger, 1994; Sect. 2.4) because the synthetic methods used are closely related to those used for aromatic diazonium salts. This is also the case for the diazotization of amino-di-, tri- and tetrazoles, which, in their neutral form, contain a heterocyclic NH group in the yff-position to the amino group. After diazotization, the NH group is very acidic. Following deprotonation the product corresponds to a heterocyclic diazoalkane. Similarly, the diazotization product of 4-(dicyano)methylaniline ((4-aminophenyl)malonitrile) may lose the CH proton. This compound is, therefore, sometimes called a vinylene homolog of diazomalonitrile (Regitz and Maas, 1986, p. 205). Summarizing the work accomplished on the synthesis of aliphatic diazo compounds by nitrosation of aminoalkanes, it has to be emphasized that precaution is absolutely necessary in its application. With few exceptions (e.g., amino-a,a'-dicarbonyl compounds), the results are unreliable for most classes of amines. This method is not recommended if the specific compound has not been described so far in the literature, or if another method (see Sects. 2.4-2.6) is available. We add here a short discussion of another method for diazotization of aliphatic amines, although it is not suitable for the generation of diazoalkanes. Diazotization under alkaline conditions is possible by using certain metal nitrosyl complexes. First, pentacyanonitrosylferrate (Fe[CN]5NO2~Naih, sodium nitroprusside) is used for diazotizations. Although it was observed at the beginning of this century that a gas, presumably N2, was evolved in the reaction of nitroprusside with amines (Hofmann, 1900; Manchot and Woringer, 1913), no reports appeared on the organic products of this reaction until 1971, when Maltz et al. determined the stoichiometry and the products of reaction with primary and secondary amines. The latter form 7Vnitrosoamines (2-14). With primary amines typical products of diazotization-dediazoniation reaction sequences were found, but no diazoalkane, in spite of the fact that pH values up to 12.7 were observed by Maltz et al. As nitroprusside is converted to the corresponding nitro complex by hydroxide ion (2-15), later experience with this method led to the conclusion that it cannot be applied at a pH above ca. 11 *. The method is not used for the generation of diazoalkanes, but for alkyldiazenolates (R-N 2 -O~, see Sect. 7.2). Evidence against the intermediacy of diazoalkane comes from experiments in D2O with benzylamine and nitroprusside. The benzyl alcohol obtained did not con* For kinetic investigations as a function of pH, see Sect. 4.1.

28

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

Fe[CN]5NO2~ + 2 R2NH -

+ 2 OT

<

^ Fe [CNlgNRgH3- + R2NNO + H+

(2-14)

»

(2-15)

Fe[CN]5NO2^ + H2O

tain deuterium at the C(a)-atom. This indicates that phenyldiazomethane was not an intermediate in the deamination. Besides this iron-nitrosyl complex, nitrosyl complexes of other transition metals can be used for nitrosation. As discussed by Bottomley et al. (1973, see also review by Bottomley, 1978), these complexes are not only sources of nitrosyl ions (NO + ) as two-electron acceptors, but also of nitroxide (NO*) as one-electron donor. Bottomley found that they are nitrosating reagents only if their NO stretching frequency is greater than 1886 cm"1. The ruthenium nitrosyls are particularly interesting with respect to their reaction with aliphatic and aromatic primary amines. We discuss them in the context of metal dinitrogen complexes (Sect. 3.3). Formation of diazoalkanes by cleavage of a secondary N-nitroso compound (R-N(NO)-R') is the subject of the next section as nitrosation is carried out in a preliminary step.

2.4 Cleavage of 7V-Alkyl-7V-nitroso Amides This cleavage is probably the most widely used method for the preparation of diazoalkanes. A wide variety of 7V-nitroso compounds can be employed. They all belong to the type 2.40, in which X is a good hydrolytic leaving group with electronwithdrawing substituents, mainly based on carboxylic or sulfonic acids, namely alkane-amides and arene-carboxamides (2.41), carbamates* (2.42), ureas (2.43), arene-sulfonamides (2.44), but also guanidines (2.45) and TV-KAf-nitrosoalkylamino)methyl]amides (2.46). A few other types of 7V-nitroso compounds have also been described as potential sources for diazo compounds, but they are not as important (see Regitz and Maas, 1986, pp. 296-298). Franchimont (1890) observed that nitrosomethyl carbamates evolved a yellow gas when treated with alkali, and von Pechmann (1894, 1895), after investigating the reaction carefully, established the structure CH2N2 for diazomethane. He recognized its close relationship to diazoacetates and the differences between it and aromatic diazo compounds. The preparation follows Scheme 2-16. * Also called urethanes.

2.4 Cleavage of N-Alkyl-N-nitroso Amides

29

.NO X—N

2.40 CHR I FT

R and R'= alkyl, aryl, H or other substituents X = R"-CO- (R" = alkyl, aryl or H)

(2.41)

R'-O-CO- (R" = alkyl or aryl)

(2.42)

R"2-N-CO- (R" = H or alkyl) Ar-SO2-

(2.43)

(2.44)

O2N-NH-C-

(2.45)

NH R' -CO-NH-CrV (R" = alkyl, aryl or OR)

(2.46)

CH2N2 + KHCO3 + ROM

(2-16)

COOR

1-Methyl-l-nitroso urea may be used in place of the carbamate (2-17) and for many years probably presented the most popular method for preparing diazomethane solutions.

+ KOH

*•

CH2N2 + KOCN + H2O

(2-17)

CO—NH2

Following Arndt (1943), 1-methyl-l-nitroso urea is added to aqueous potassium hydroxide and ether at 5 °C in a flask fitted with a condenser set for distillation. On heating the mixture to the boiling point of ether, the yellow diazomethane is codistilled with the ether and collected in ice-cooled ether contained in another flask. On completion of the reaction, the distillate becomes colorless. For the synthesis of substituted diazoalkanes, ethanol (Kusmierek et al., 1987; for diazophenylmethane) or two-phase systems, e. g., aqueous NaOH and methylcyclohexane (Kirmse and Buschhoff, 1967), are recommended instead of aqueous solutions.

30

2 Methods for the Preparation of Alkane, Alkene, and Alky ne Diazo Compounds

1-Methyl-l-nitroso urea was subsequently shown to be a potent carcinogen (see Sect. 4.2), and its use is now discouraged. For the synthesis of diazoalkanes, for which no other route is described in the literature, 7V-alkyl-7V-nitroso ureas may still be the reagent of choice. This is the case, for example, for diazo acetaldehyde (2.48), which was obtained (2-18) by Abdallah et al. (1983) by cleavage of 7V-(2,2-dimethoxyethyl)-7V-nitroso urea (2.47). The corresponding 7V-nitroso urea was also used successfully for the preparation of 4-(2-diazoethyl)-2,3,3-trimethylcyclopentene (2.49) by Adam et al. (1985). Various other methods failed to lead to this diazoalkane. NO (CH30)2CH— CH2 — N

*-

0=CH— CH=N2

+ 2 CH3OH

, +

2.47

H3C

+ OK" -

(2-18)

-nrN OCN

CH3

2.49

Like nitroso carbamates, l-alkyl-3-nitro-l-nitroso guanidines (2.45) also cause skin irritations; they are also potent mutagens (Adelberg et al., 1965). It was, therefore, recommended to replace all these nitroso compounds of relatively low molecular mass, high volatility and lipophilicity by 7V,7V'-dimethyl-TViTV'-dinitroso tetraphthalamide (2.50), trade name Nitrosan; Moore and Reed, 1972) or by TV-nitrososulfamides such as 7V-methyl-7V-nitroso-4-toluenesulfonamide (2.51, trade name Diazald; De Boer and Backer, 1963). The nitroso compound 2.50 is added to a mixture of ether, diethylene glycol monoethyl ether, and aqueous NaOH at 0°C. The formation of diazomethane is

NO

H3C

C=O

2.50

2.4 Cleavage of N-Alkyl-N-nitroso Amides

31

rapid at this temperature. Ether is distilled in 2-2.5 h. The distillate contains the diazomethane in 76-80% yield. Determination of the yield of diazomethane in codistillates of ether or other solvents is achieved, for occasional cases, most conveniently by titration: an exactly weighed sample of benzoic acid (ether solution) in excess over the expected amount of diazomethane is added to an aliquot of the diazomethane solution. Methyl benzoate is formed rapidly and almost quantitatively. The unreacted benzoic acid is then titrated with 0.1 M NaOH solution. For routine analyses spectrophotometric measurement at the absorption maximum of diazomethane (400 nm) is recommended. For Af-methyl-Af-nitroso-4-toluenesulfonamide (2.51), the cleavage of the N —S bond is more difficult than the cleavage of the corresponding N - C bond in carboxamides. The reaction is run either in carbitol —water —KOH mixtures* at 50-70°C, giving gaseous diazomethane in 48-78% yield, or in the presence of ether, giving ether solutions of diazomethane in up to 90% yield (Hudlicky, 1980). With other TV-alkylated 7V-nitroso-4-toluenesulfonamides, yields may be considerably lower, for example, in the preparation of alkoxy diazoalkanes (Groth et al., 1964), as the following figures demonstrate: 1-diazo-l-ethoxyethane 47-49%, l-diazo-3-methoxypropane 5-8%, and l-diazo-4-methoxybutane 3-5%. If the yield with 7V-alkylated 7V-nitroso-4-toluene-sulfonamides is not suitable, the corresponding urea derivatives may give more satisfactory results, as shown by Adam et al. (1985) for the synthesis of 4-(2-diazoethyl)-2,3,3-trimethylcyclopentene (2.52, X = CH2CHN2). The synthesis via the 4-toluenesulfonamide and its 7V-nitroso derivative (2.52, X = CH2CH2-N(NO)SO2C7H7) failed, but the route via the corresponding N-nitroso urea (N-nitroso-N-[2-(2,2,3-trimethylcyclopent-3-en-l-yl)ethyl]urea, 2.52, X = CH2CH2N(NO)CONH2) gave the diazo compound in 46% yield.

2.52

Sekiya et al. (1976) found that the terephthalamide 2.50 and the 4-toluenesulfonamide 2.51 are still not entirely stable. They recommended replacing these starting materials for the synthesis of diazomethane by A/r-[(N-alkyl-7V-nitrosoamino)methyl]benzamide (2.53). The preparation is carried out in a stirred diethylene glycol solution with a large excess of KOH, over which petroleum ether is layered. The temperature is kept constant at the boiling point of petroleum ether. As can be seen from Scheme 2-19, it is claimed that dibenzoylaminomethane (2.54) and form-

* Carbitol is the trade name of Union Carbide for diethylene glycol monoethyl ether (2-(2-ethoxyethoxy)ethanol),

32

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds C6H5CON—CH2—N—CH2R

H 2.53

+ OhT

N^ O

C6H5CONj CH2-^N — CH2R

HO-

C6H5CON=CH2

RCH2—N2—O-

(2-19)

hH2O

C6H5CONHCH2OH

= N2 + OH"

C6H5CONH2 + CH2O C6H5CON=CH2

(C6H5CONH)2CH2 2.54

aldehyde are formed in addition to the diazoalkane. The formaldehyde apparently formed in that sequence of reactions has not, however, been detected. This mechanism is still tentative. Compound 2.53 is commercially available (Diazald II). Aldrich (1989) developed an apparatus for the non-hazardous preparation of diazomethane from l-methyl-3-nitro-l-nitroso guanidine (2.45, R = R/ = H), which is convenient for the generation of one mmole or less of diazomethane, and three kits for the generation from Af-methyl-7V-nitroso-4-toluenesulfonamide (Diazald) for the preparation of up to 50, 100, or 200 mmoles, based in part on a design of Hudlicky (1980). These kits allow generation of diazomethane solutions in a closed system. Such systems are necessary due to the extreme toxicity of diazomethane, causing pulmonary edema when the vapor is inhaled. For the generation of deuterated diazomethane (CD2N2) or 13C-diazomethane Diazald-N-methyl-d3 (98% D) and -7V-methyl-13C (99% 13C) are available. (D2)Diazomethane can also be generated in the kits by using the deuterated Diazald precursor, but in deuterated solvents (Aldrich, 1989). For the preparation of diazoethane (2-20) 4-(A^ethyl-A^-nitrosoamino)-4-methylpentan-2-one (7V-nitroso-/?-ethylamino-isobutyl methyl ketone, 2.55) is commercially available (Fluka). The method was developed by Adamson and Kenner (1937). The

2.4 Cleavage of N-Alkyl-N-nitroso Amides

33

H3C/

(2-20)

starting material for 2.55 is 4-methylpent-4-en-2-one (mesityl oxide), which is nitrosated after nucleophilic addition of ethylamine to the ethylenic double bond. Diazoethane is obtained in 50% yield by alkaline cleavage with sodium 2-propoxide in 2-propanol and ether. The method of Adamson and Kenner (1935, 1937) is also applied for higher homologs, but the yields decrease (1-diazooctane: 16%) due to the higher instability of these compounds (see Sect. 2.2). As shown in (2-20), mesityl oxide is regenerated in the reaction. 7V-Alkyl-7V-nitroso carbamates (2.42) are also frequently used for the preparation of homologs of diazomethane. Although not strictly belonging to this section, the method of Janulis and Arduengo (1983) for the formation of 5-diazo-l,2,3,4-tetrakis(trifluoromethyl)cyclopenta-l,3-diene (2.57) may be mentioned (2-21). It is related to Tedder's (1957) 'direct introduction of the diazonio group' (see Zollinger 1994, Sect. 2.6). The cyclopentadienide salt 2.56 is mixed with nitrosyl tetrafluoroborate at -78°C and after addition of acetonitrile slowly warmed to room temperature. The 5-nitroso derivative formed is treated in CH2C12 with an aqueous solution of KNO2 at -30°C, and aqueous HCI is added. The product is obtained from the organic phase at room temperature.

1. +N0 BF4~ .

^I(CH3)4

-

2. KNO2/HCI

1-

F

3Cx/

N2 II C

xs,.CF3

\\

^

If

J /I

F3C

(2-21)

CF3

2.57

An analogous method, in which l,6-diphenylhexane-l,3,4,6-tetrone (2.58; Ar = C6H5) is nitrosated with N2O3 in CH2C12 at -30°C to yield the 2,5-bis-diazo derivative 2.59 (2-22), was found by Rubin et al. (1980).

Aiv ^ChU /ChW JVr ^ ^ ^ ^ ^ ^ O

O

O 2.58

N203

O

AK

N2 II

C^ ,C^ .Ar ^^ ^ ^ ^ O

Ar = C H

6 5 etc'

N2 II

O 2.59

O

O

(2-22)

34

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

2.5 Syntheses Starting with Ketones or Aldehydes By three reaction types (3), (4), and (5) in Table 2-1 of Sect. 2.2, ketones or aldehydes are used as starting materials. Therefore, it is reasonable to treat them together in this section. At the end (Subsection 2.5.4) a related diazomethane synthesis (depicted many decades ago by Staudinger) will be added, although it is not strictly related to this section. From the synthetic point of view, it is not particularly interesting, but mechanistically it is worthy of discussion because nitrilimine, an isomer of diazomethane, is probably formed as a steady-state intermediate in this reaction.

2.5.1 Dehydrogenation of Hydrazones Curtius discovered both the first synthetic route to aliphatic diazo compounds by nitrosation of amines (1883, see Sect. 2.3) and, in 1889, also their preparation by dehydrogenation of hydrazones, i.e., reaction (3) in Table 2-1. He treated the monoand the bis-hydrazone of benzil (1,2-diphenylethanedione, 2.60) with yellow mercury (n) oxide (2-23). With the monohydrazone 2.61, he obtained 2-diazo-l,2-diphenylethan-1-one (azibenzil, 2.62). The corresponding bis-diazo compound (2.64) of

C H5C
\>

2.60 + HgN—NH2

T

-HgO

/\ 0

H5C/

<2'23>

x\O

X

H5C6/

2.61

2.62

+ HgN—NH2

//N-NH, C

M-NH,

N2

C

"

,CX

2.63

H5C6x ^-2H S 0

C H5C6/ ^

2.64

^ -2N 2

C

"

C i^

2.65

2.5 Syntheses Starting with Ketones or Aldehydes

35

the bis-hydrazone 2.63 was not, however, sufficiently stable for isolation. Two equivalents of nitrogen are eliminated, leading to 1,2-diphenylethyne (2.65). Tsuji et al. (1983) found a simpler and cheaper modification of the classical dehydrogenation with the toxic Hg(n) or Pb(iv) salts (see Cope et al., 1963), namely the oxidation in an O2 — pyridine — CH2C12 system in the presence of catalytic amounts of CuCl. This method is very useful for the synthesis of ethyne derivatives and cycloalkynes (review of cycloalkynes: Meier, 1991). If the phenyl rings in benzil (2.60) are replaced by pyridin-2-yl rings, the corresponding mono- and dihydrazones do not give l,2-(dipyridin-2-yl)ethyne, but ring closure of the initially formed mono- and bisdiazo compounds, respectively, to the corresponding l-[(pyridin-2-yl)carbonyl]pyrido[l,2-c][l,2,3]triazole (2.66) and 1,1'bis(pyrido[l,2-c][l,2,3-triazole) (2.67) takes place, as shown by Boyer and Goedel (1960). This observation demonstrates that the N(/?)-atoms in diazo compounds such as 2.62 and 2.64 are electrophilic and, therefore, able to react with nucleophilic centers. This type of reaction is successfully competitive with dediazoniation only if the nucleophilic center is very close. Indirectly, one can conclude that the dediazoniations in (2-23) have half-lives comparable to those of diffusion-controlled reactions.

2.66

2.67

Nowadays, hydrazone dehydrogenation with HgO is probably the synthetic method, next to cleavage of 7V-nitroso compounds, that is most frequently used for diazoalkanes substituted with alkyl, aryl, heteroaryl, or carbonyl groups. The reaction must be conducted in an apolar solvent. Ether is most frequently used, but benzene, furan, dioxane, and hexane are also used. In more polar solvents such as 1,2-dimethoxyethane, diglyme, ethanol, or tetrahydrofuran the corresponding nitrile may be formed (Mobbs and Suschitzky, 1971). Yields can often be increased by the addition of sodium sulfate, which binds the water formed, and small amounts of alcoholic KOH (e.g., 0.05 equivalents, see Day et al., 1966). Miller (1959) proposed the mechanism (2-24) for the dehydrogenation, explaining the role of the potassium ethanolate in deprotonating the mercury-hydrazone complex. Mechanism 2-24 is difficult to understand on the basis of observations made by Droescher and Jenny (1968). These authors mentioned that well crystallized, very pure HgO is not active for dehydrogenation of hydrazones. When a Guinier-Preston diagram * of very pure HgO was compared with that of a sample that was activated

* The Guinier-Preston technique is an X-ray method that allows detection of atoms of higher mass on solid surfaces. It is applied predominantly for metal alloys.

36

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

X

X X

C = N—NH2

+ HgO

X

*-

Y

C = N—NH2— HgCT

Y

X

\

-

C = N—N—HgOH \/ Y I

+ -QR

X

•«

~ HOR

\

C = N—NH—HgOH

. /

Y

(2-24)

I

X X

C = N=N + HgOhT

'

I

Hg + "OH

by potassium ethanolate, it was shown that the latter is more diffuse and has 12 lines less than the purified sample. If the oxide has additional lines, due to the presence of metallic mercury, it is also not active. These observations make the mechanism for activation proposed by Miller (1959) questionable. A definite decision is unfortunately not possible, as the problem was not studied in detail either by Droescher and Jenny or by Miller. Droescher and Jenny (1968) made their observations on the activity of HgO in the context of synthesizing (4-methoxybenzoyl)(4-methoxyphenyl)-diazomethane (2.69) from the corresponding hydrazone 2.68. They obtained 2.69 in 80% yield in tetrahydrofuran at — 20 °C. With inactive HgO but in the presence of potassium ethanolate they observed a dediazoniation. It is likely that desoxyanisoin (2.70) is formed in a Wolff-Kishner reaction (2-25). Klaerner et al. (1986) optimized the preparation of fresh and active HgO. It is important to work in the dark because light deactivates HgO. Stoichiometrically, one equivalent of HgO is necessary for the dehydrogenation of a hydrazone. Examples have been published in Organic Syntheses: Smith and Howard (1955) described the procedure for diphenyldiazomethane, obtained from benzophenone hydrazone in petroleum ether in 89-96% yield. The necessity for the absence of moisture is emphasized, but no activation of the mercury(n) oxide seems to be required. Andrews et al. (1988) have reported on the dehydrogenation of acetone hydrazone to 2-diazopropane (70-90% yield) in ether in the presence of catalytic amounts of KOH in ethanol. There are also cases where two equivalents are used, e.g., the procedure for (benzoyl)(phenyl) diazomethane (2.62, yield 87-94%) published in Organic Syntheses by Nenitzescu and Solomonica (1943). Neither these nor other authors have explained, however, why two equivalents would be necessary. Several other dehydrogenation reagents have been recommended for hydrazones. Lead(iv) tetraacetate in dichloromethane was used by Barton et al. (1974) to form diphenyldiazomethane from benzophenone hydrazone. The authors claim that a 100% yield can be obtained and that the method is better than dehydrogenation with

2.5 Syntheses Starting with Ketones or Aldehydes

37

OCH3

OCH3

|

OCH3

+inacti^

HgO

KOEt

Y

(2-25)

yellow mercury(n) oxide. In a contribution to Organic Syntheses, Middleton and Gale (1988) used Pb(OAc)4 for the preparation of bis(trifluoromethyl)diazomethane (2-diazo-l,l,l,3,3,3-hexafluoropropane). Benzonitrile was used as solvent. This is rather surprising, considering the general experience on the effect of solvent polarity mentioned above. As acetic acid is formed when using lead(iv) tetraacetate, this dehydrogenation reagent can only be used for the synthesis of diazoalkanes with low acid sensitivity, i. e., those containing electron acceptor substituents at the diazo Catom, such as CF3 (above), CN (diazomalonitrile, Ciganek, 1965 a), or phenylsulfonyl (Diekmann, 1963). Lead(iv) tetraacetate can be used only for the syntheses of substituted diazoalkanes with a low electron density at the C(a)-atom, which decreases the sensitivity to protonation. Manganese(iv) oxide must be in activated form in order to be effective. It is prepared from potassium permanganate and manganese(n) sulfate tetrahydrate in alkaline solution (Attenburrow et al., 1952; Morrison et al., 1961). Besides some diazoalkanes with aromatic, heteroaromatic, or alicyclic rings at the diazomethane C-atom (e. g., Nagai and Hirata, 1989, for aryldiazomethanes), it is often used for the synthesis of a-diazo ketones, if the reaction of an acyl halide with a diazoalkane (first step of the Arndt-Eistert synthesis, see Sect. 8.6) is not successful. For these compounds, of the three major routes starting from 1,2-dialkylated or 1,2-diarylated ethanones (Scheme 2-26), Hauptmann and Wilde (1969) demonstrated that pathway B is widely applicable. A ketone is first brominated at the C(a)-atom (Hauptmann et al., 1965). The a-bromoketone then reacts with three equivalents of hydrazine leading to a-ketohydrazone 2.72 (for the stoichiometry, see Scheme 2-27). For the dehydrogenation to the a-diazo ketone, MnO2 in chloroform is used. With this

38

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds RCOCH2R' 2.71

RCOCOR

nvywwi ILJI ri

i iwwwi n i

RCOCHBrR' + 3 H2N — NH2

^

lf.

nf,.\

(2-26)

RCOCR' + H2N — NH3Br

+ 2 NH3

(2-27)

NNH2

method, Hauptmann's group synthesized 37 a-diazo ketones, among them nine previously unknown. Pathway A has already been discussed (2-23). In the reaction sequence C, introduction of the formyl group by a Claisen ester condensation with a formic acid ester is followed by treatment with 4-toluenesulfonyl azide, i. e., by a diazo transfer reaction (Regitz and Menz, 1968; see Sect. 2.6). MnO4 is also frequently used for the synthesis of bis- and tetradiazo compounds from the corresponding bis- and tetrahydrazones (Teki et al., 1986; Hannemann et al., 1988 and references therein). Silver oxide and silver carbonate have the advantage of a higher rate of reaction with hydrazones relative to mercury(n) oxide. Therefore, these reagents are mainly used for the synthesis of labile diazoalkanes. Ag2O is, for example, suitable for the dehydrogenation of cyclohexanone hydrazone to give diazocyclohexane (2-28), whereas with HgO, the main product is di(cyclohexyl)azine (Heyns and Heins, 1957). Fetizon et al. (1975) found that diazoalkanes can be obtained with Ag2CO3 in refluxing benzene in a very short time in yields similar to those obtained with HgO or MnO2. If the reaction time is too long, however, azines and the starting ketone are formed in similar amounts as with MnO2 (Fetizon et al., 1973).

HgO/C6H6 - 5 t o + 20<€ N-Nx

A

^

N II J^

Ag 2 0/xylene -35to-15<€ ^ yield 20-27%

(2-28) '

'

2.5 Syntheses Starting with Ketones or Aldehydes

39

Nickel peroxide is used occasionally. Nakagawa et al. (1966) reported a 100% yield of phenylbenzoyldiazomethane at 0°C, but at room temperature benzophenone was found. Upon comparison with the procedure of Nenitzescu and Solomonica, which leads to an 87-94% yield at room temperature with HgO (see p. 36), one is skeptical with respect to the work of Nakagawa et al. Among other dehydrogenation reagents, we should mention triphenylbismuth carbonate (97% yield of diphenyldiazomethane, Barton et al., 1979), and sodium hydride in THF, which was used by Padwa et al. (1983 a) to prepare (E)-l,4-diphenyl-4-diazobut-l-ene (2.74) from (£)-!,4-diphenylbut-3-en-l-one 7V-tosylhydrazone (2.73)* (2-29). It was also used by Krebs et al. (1984) for the synthesis of diazocyclopentane, -hexane and -heptane derivatives with two methyl groups at the two C-atoms in the positions a- and a'- to the diazo C-atom. At the same time, Cullen et al. (1984) published the synthesis (2-30) of the corresponding diazocyclopentene, 4-diazo-3,3,5,5-tetramethylcyclopentene (2.78). They added first an equivalent of bromine and afterwards triphenylphosphine to the corresponding hydrazone 2.76. The triphenylphosphanylidene derivative 2.77 was isolated and heated for two hours without solvent at 185 °C. NNHTs

II pH 6

2.73

*

2.74

(2-29)

1. + Br 2 /C 6 H 6

- -

- '

-'

- '

p-30)

2. P(C6H5)3 N(C2H5)3

2.76

2.77

2.78

* The 4-diazobut-l-ene 2.74 is formed in equilibrium with the intramolecular 1,3-cycloaddition product, 3,6-diphenyl-l,2-diazabicyclo[3.1.0]hex-2-ene 2.75.

40

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

A new oxidation reagent for the synthesis of diazoalkanes from hydrazones is 7,7-diacetoxy-iodobenzene (phenyliodosoacetate): it was used by Smith's group (Bedford et al., 1981) for the formation of 5-(diazomethyl)-l,4-diphenyl-l,2,3-triazole from the hydrazone of l,4-diphenyl-l,2,3-triazole-5-carbaldehyde in cyclohexylamine and CH2C12 at -40°C (2-31).

Hp6_|(o-CO-CH3)2

^

„.

^

Recently, two methods were published that have attracted some interest, because no metal salts are necessary as oxidation reagents. Shi and Xu (1990) found that substituted (trifluoromethyl)-diazoalkanes (CF3CRN2, R = alkyl or aryl) are obtained by refluxing trifluoromethyl ketones and 2,4,6-tri(isopropyl)benzenesulfonyl hydrazone in a methanolic solution of KOH. Kumar (1991) synthesized a-diazocarbonyl compounds under tri-phase phase-transfer catalysis using a polystyrene-supported (tributyl)(methyl)-ammonium chloride catalyst, methanesulfonyl chloride, NaN3, and methylsulfonyl azide in 1,2-dichloroethane and a carbonyl-activated substrate (69-94% yield).

2.5.2 Bamford-Stevens Reaction The formation of aliphatic diazo compounds by cleavage of 4-toluenesulfonyl hydrazones into diazoalkanes and 4-toluenesulfinic acid, the Bamford-Stevens reaction, is closely related to the dehydrogenation of alkylhydrazones discussed at the beginning of this section. In the dehydrogenation reaction a hydrogen molecule must be formally eliminated from the N(/?)-atom of a hydrazone by an oxidizing agent (Scheme 2-32, pathway A). Toluenesulfonyl hydrazones, the starting compounds in the Bamford-Stevens reaction, are normally obtained from aldehydes or ketones with 4-toluenesulfonyl (or other arenesulfonyl) hydrazides (pathway C). They can also be considered as reaction products of alkyl hydrazones with 4-toluenesulfonyl chloride (pathway B), i. e., of a reaction in which one of the hydrazone H-atoms is eliminated as a proton. The second H-atom is lost in the Bamford-Stevens reaction, again as a proton, but combined with the cleavage of the N - S bond resulting in the formation of a 4-toluenesulfinate ion, i. e., a sulfur compound at the oxidation level SIV, whereas the starting 4-toluenesulfonyl chloride was at the level SVI. In other words, the oxidizing reaction in pathway B is built into the molecule of the reaction intermediate, the 4-toluenesulfonyl hydrazone, whereas in the dehydrogenation method A an "external" oxidizing reagent Ox has to be added. An alternative

2.5 Syntheses Starting with Ketones or Aldehydes

H2N—NH22 —2 —+» -H20

\ C=

y/

B + H2N-NH-SQ2Ar

-H20

41

N_Nu 2

A D

' 7/

-HCI

(2-32)

method with an internal oxidation was suggested by Dana and Anselme (1975). As shown in D, an arylsulfenyl chloride (Ar = 2-nitrophenyl) is used, which forms a sulfenylhydrazone as intermediate. Methylsulfenyl chloride can also be used (Shelnut et al., 1975). So far as we can see, this method has not been used again, probably because of the instability and poor availability of sulfenyl chlorides. The Bamford-Stevens sequence of reactions was used first by Borsche and Frank (1926), but its synthetic potential was discovered only 26 years later by Bamford and Stevens (1952) and was subsequently applied by many chemists. Aryldiazomethanes (Ar —CH = N2) are readily prepared by exposure of the arenecarbaldehyde tosylhydrazone to base (Dudman and Reese, 1982). The pink-red naphthalen-1-yldiazomethane, for instance, is obtained by addition of sodium methoxide to a suspension of 1-naphtaldehyde 4-toluenesulfonyl hydrazone in methanol. The diazoalkane can be isolated by dilution with water (Bailey et al., 1983). A surprisingly high yield of 98% was reported by Just et al. (1988) for the Bamford-Stevens synthesis of bis(4-nitrophenyl)-diazomethane, using 1 M NaOH at 75 °C (3 h). Shechter's group (Kaufman et al., 1965) showed that the Bamford-Stevens reaction can be exploited in vacuo instead of in solution. A series of corresponding examples was provided by Creary (1990) for Organic Syntheses (see below). Wulfman et al. (1988) showed that phase-transfer catalysis improves the method further. Jin et al. (1992) found a convenient modification of the Bamford-Stevens reaction for the synthesis of 1-diazo-2,2,2-trifluoroethane (2.80), a compound known to be dangerous if prepared by methods involving nitrosation of the corresponding amine. Jin et al. described a method in which 2,2,2-trifluoro-l-triphenyl-silyl)acetaldehyde 2,4,6-triisopropylbenzenesulfonylhydrazone (2.79) is converted to the diazo compound 2.80 in a onestep reaction, which is assumed to follow mechanism (2-33). Optimum yields (not given) are obtained in THF or methanol in the presence of triethylamine, or in methanol with K2CO3.

42

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds NNH —SO2Ar

HB+

NN—SO^r +B

F3C-C-Si(C6H5)3

>

F3C-C-Si(C6H5)3

2.79

(2-33)

(H5C6)3Si-O—S—Ar

+

F3C—CH=N2

Wtta* J C/N—S—Ar

-*

^N F3C—CH

2.80

/T~\

°

/

Ar =

The Bamford-Stevens synthesis is related to the Shapiro reaction (Shapiro and Heath, 1967; reviews: Shapiro, 1976; Adlington and Barrett, 1983), in which a 4-toluenesulfonyl hydrazone of an aldehyde or a ketone is treated with at least two equivalents of a very strong base, usually, methyllithium (see Organic Syntheses examples of Chamberlin et aL, 1983, and Shapiro et al., 1988). The Shapiro reaction leads to an olefin by a hydrogen shift. The mechanism has been proposed by Casanova and Waegell (1975) as given in (2-34). This mechanism involves a diazenide anion 2.81 as intermediate.

N—N-\Ts (2-34) H

2°

i

.

For the Bamford-Stevens reaction, smaller amounts of methyllithium or other bases, such as sodium alcoholates, LiH, NaH, sodium ethylene glycolate, or NaNH2 are used. The consequence is that the C - H group adjacent to the hydrazone moiety does not dissociate (2-35). Padwa et al. (1983 b) applied a similar process (2-36, NaH in THF) for the synthesis of the diazoalkene 2.82.

2.5 Syntheses Starting with Ketones or Aldehydes

rr I

^

H

N—NH—Ts

—- -nbase

I

H

~^~ ~?~r ™ slow

N—N-^Ts

43

I

H

N2

Ts: see (2-34)

NNH-Ts

N2 H5C^

^^^

f2"36)

" "

2.82

i~. M m\

-r-

^^

Ts: see (2-34)

The problem concerning the neighboring CH group does not exist in the Bamford — Stevens reaction of 2,2,4,4-tetramethylpentan-3-onej4-toluenesulfonylhydrazone (2.83), which gives di(tert-butyl)diazomethane (23*4), with sodium hydride in tetrahydrofuran in 90 % yield (Barton et al., 1974) (2-37). (CH3)3Cx C = N—NHSOoAr

>~ THF

(CH3)3C

(CH3)3Cx £ = N2 (CH3)3C

2.83

(2-37)

2.84

Depending on the solvent used, the reaction often does not stop (or is not stopped by intention) at the diazoalkane stage, but goes on to carbenes or to carbocations. Carbenes and their reaction products (olefins) are formed in apolar systems, carbocations and subsequently, their stable products in protic solvents (2-38).

— C— C—

I— > H

I H

II N2

— C— CH — I I H N2+

J I

-C = C—

H

I

-N2

+

—C —CH—

H

(2-38)

+ Nu

I

>- —C —CH —

H

Nu

44

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

The Bamford- Stevens reaction is frequently used not for the isolation of aliphatic diazo compounds, but for the synthesis of the products obtained by dediazoniation either by the carbene or the carbocation mechanisms in (2-38). As 4-toluenesulfonylhydrazones are fairly stable under Bamford-Stevens conditions, the reactions must be carried out at higher temperature, which is, of course, a disadvantage when it is desired to stop the reaction at the diazoalkane stage. Yields above 90 % can, however, be obtained in some cases, particularly for the synthesis of 9-diazofluorene (Dudman and Reese, 1982). Dudman and Reese (1982) showed also that the use of 2,4,6-triisopropylbenzenesulfonylhydrazone is preferable to that of 4-toluenesulfonylhydrazone because of higher yields. This result is likely to be due to greater release of steric compression in the decomposition of 2,6-substituted arenesulfonylhydrazones. Because of the low thermal reactivity of 4-toluenesulfonylhydrazones their photolytic cleavage was successfully investigated for the synthesis of 13-diazospiro[11.12]tetracosane (2.85) in hexane at 16 °C. Nickon and Zurer (1981) obtained 2.85 by this method in 95 % yield. It is important to use a Pyrex filter (i. e., transmitting UV light up to 270 nm). If the light between 220 and 270 nm is not transmitted, spiroalkenes are obtained.

2.85

Under more vigorous conditions, the Bamford-Stevens reaction yields diazoalkanes only as unobservable, metastable intermediates. The carbene formed is also metastable. This procedure is used, however, for the synthesis of compounds that are carbene products. Pyrolysis in vacuo without a solvent has been successfully used in recent years for aryldiazomethanes (Creary, 1990; Meese, 1985) and for cycloalkyldiazomethanes (Chari et al., 1982). Heating the sodium salt in an apolar solvent (e.g., hexane) can also be recommended (e.g., for l-diazo-4,4-dimethyl-l,4-dihydronaphthalene, Mathur et al., 1985, or for diazoindenes, Kapur et al., 1988). Under extremely careful exclusion of moisture it is possible to obtain 3-diazo-2-oxobicyclo[2.2.1]heptane (2.86) (Yates and Kronis, 1984) in good yield. Yet, diazobicycloalkenes without an a-keto group, e.g., 4-diazobicyclo[3.2.1]oct-2-ene (2.87) and -octa-2,6-diene (2.88) are formed only in modest yields (Murahashi et al., 1982), as well as 7-diazocyclohepta-l,3,5-triene (2.89; Kuzaj et al., 1986). No drastic reaction conditions are required for Bamford-Stevens reactions of adiketone mono-4-toluenesulfonyl hydrazones. The conditions are similar to those of quinone mono-4-toluenesufonyl hydrazones discussed in Section 2.6. a-Diazophosphonates and a-diazophosphinates are frequently synthesized with the help of the Bamford-Stevens reaction, as a-oxophosphoryl compounds (2.90) are easily available by the Michaelis-Arbuzov reaction (2-39).

2.5 Syntheses Starting with Ketones or Aldehydes

45

N2 2-86

"

2.87

I P R'CT ^OR'

+

)c-R" //

*

2.88

!..»

FTO—P-C V

2.89

(2-39)

2.90

The 4-toluenesulfonylhydrazones obtained from the a-oxophosphoryl compounds 2.91 form two isomers which can be identified easily due to the hydrogen bond in the (Z)-isomer 2.92 (2-40). Both isomers readily undergo cleavage to the common adiazophosphoryl compound 2.93, as shown by Regitz and coworkers (Regitz et al., 1968; Scherer et al., 1972; Felcht and Regitz, 1975; Theis and Regitz, 1985a, 1985b).

2.91 Ts—NH—NH2 A, C2H5OH

C6H5

H5C2O

'/

H5C20

C6H5 I

^>

\ 2.92

KOH

2.93

M

46

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

2.5.3 Forster Reaction The third reaction type to be discussed in this section is the Forster reaction. It was discovered by Forster in 1915, as he had obtained (benzoyl)(phenyl)diazomethane (2-diazo-l,2-diphenylethan-l-one, 2.62) by treatment of (Z)- and (£)-benzil monooxime ((Z) = 2.95) with sodium hypochlorite and ammonia (which readily forms chloramine). a-Keto-monoximes like 2.95 are obtained easily from a-methylene-containing ketones (e.g., 2.94) by the oximation reaction, i.e., a nitrosation with a nitrous acid ester followed by a C -»O proton shift (2-41).

(2-41) . .

~~

O

\^s

HgC/

X

NOH

HgQ/

\>

2.94

Forster's method was ignored for many decades, until it was realized that it is useful for the synthesis of a-diazo ketones (Horner et al., 1958, 1959; Cava et al., 1958; Jung et al., 1985). It can be used also for the synthesis of unsubstituted diazoalkanes, e.g., for diazomethane starting from formaldehyde (Rundel, 1962), but it has no importance for such syntheses. This is also the case for the synthesis of aryldiazoalkanes such as diazophenylmethane, diazodiphenylmethane and diazofluorene (Meinwald et al., 1959). The application of the Forster reaction to the synthesis of a-diazo ketones is particularly important for derivatives of indanone and steroidal ketones with a methylene group in the a-position to the carbonyl function. The reaction allows functionalization of the a-methylene group. Examples include the synthesis of 2-diazo-3,3-diphenyl-indan-l-one (2-42; Cava et al., 1958) and 16-diazo-3/?-hydroxy-androst-5-en-17-one (2-43, Muller et al., 1962; Wheeler and Meinwald, 1988). O 1. Oximation O

Cnr^tfir

vnnsvtim-1

.^^^ <J^

I] ^Y**

\

(2-42)

a,a'-Bis(diazo) ketones can also be obtained with this method using a,a'-bis(methylene) ketones. An example is 2,6-bis(diazo)cyclohexan-l-one (2.96, Kirmse, 1959; Trost and Whitman, 1974). Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

2.5 Syntheses Starting with Ketones or Aldehydes O

47

O

2.96

2.5.4 Miscellaneous Reactions A mechanistically interesting method for the formation of diazomethane was found by Staudinger and Kupfer (1912). They obtained diazomethane from hydrazine and chloroform in 25 % yield. In spite of the ready availability of the reagents, the method is not attractive for the synthesis of diazomethane, even after Sepp et al. (1974) were able to increase the yield to 48% by adding small amounts of 18-crown-6*. The mechanism (2-44), which was tentatively proposed by Hegarty (1978, p. 579), is, however, interesting because of the hydrazonyl chloride 2.97 formed primarily; elimination of HC1 gives the zwitterionic nitrile imine 2.98, which is an isomer of diazomethane (for a discussion of diazomethane isomers, see Sect. 5.4).

— ? Hf I

HCCI3 + NH2NH2

^

N

C = N—NH2

" ™ >

H—C = N—N—H

* Systematic name of 18-crown-6 is 1,4,7,10,13,16-hexaoxacyclooctadecane.

(2-44)

48

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

A new method for the synthesis of 1,1-dialkyldiazomethanes (2.101) has been developed by Warkentin's group (Majchrzak et al., 1989). 7V-Acylhydrazones of ketones (2.99) are oxidized with lead tetraacetate to 2,5-dihydro-l,3,4-oxadiazoles (2.100). This intermediate undergoes a photolytic cleavage if irradiated with UV light (300 nm) at room temperature in benzene (2-45). R" O=C R \ _ R/

\

/

Pb(OAc)4/CH3OH

NH

Rv

Y/

Q

\/

OCH3

*- D,/\ T^n" R \ _ / R

2.99

2.100

hv

*• _ R"—COOCH3

R

\

R//

C = N2

(2-45)

2.101

Several other syntheses of diazomethane have been reported, but they are rarely used (see Regitz and Maas, 1986, and in Klamann and Hagemann's volume of Houben-Weyl, 1990).

2.6 Diazo Transfer to Active Methylene Compounds In diazo transfer reactions both N-atoms, i. e., the entire diazo group, are introduced into a suitable substrate from a diazo donor (2-46). In most cases this transfer reagent is a sulfonyl azide (Y=N 2 = Ar-SO 2 N=N 2 or R-SO 2 -N=N 2 ), from which the N(/?)- and N(y)-atoms will form the diazo group in the product. There are, however, also cases in which the diazo group of an aromatic diazonium ion or of a diazoalkene is transferred. Such examples are of minor importance. Y=N2 + X

^

Y + N 2 =X

(2-46)

We will discuss the diazo transfer reactions in two parts (Sects. 2.6 and 2.7) because of the broad variety of methods and compounds involved. Mechanistically, this classification is, however, not necessary. The first scientist who carried out a diazo transfer reaction was Dimroth (1910). The process was rediscovered by Curtius and Klavehn (1926) — more than 40 years after Curtius established the first diazoalkane synthesis, and two years before he died (see Sects. 1.1 and 2.3) — and again by Doering and DePuy in 1953. Their synthesis of diazocyclopentadiene from cyclopentadienyllithium and 4-toluenesulfonyl azide (tosyl azide, see Zollinger, 1994, page 33, Scheme 2-31) has, however, only been occasionally used for other diazo transfer reactions (e.g., by Farnum and Yates, 1960;

2.6 Diazo Transfer to Active Methylene Compounds

49

Fuseo et al., 1963; Rosenberger et al., 1964). As a reaction of general scope, it was not recognized for another decade. One reason may have been that diazocyclopentadiene was considered — in our opinion correctly — as an aromatic diazonium zwitterion. Furthermore, diazo group transfer from 4-toluenesulfonyl azide to phenoxide ions yields also aromatic diazo compounds (see Zollinger, 1994, Sect. 2.6). The method was, however, not yet tested at that time for the synthesis of typical diazoalkanes. Systematic work on synthetic applications of diazo transfer was initiated by Regitz (1964a-c, 1965b). He soon realized the general character of the method (1967) and coined the term diazo group transfer reaction. In this book, we employ simply diazo transfer reaction, as already used by March in Advanced Organic Chemistry (1992): Diazo transfer reagents may contain various groups as donors of two N-atoms, namely azido, diazo, or diazonio groups. Therefore, we consider the (shorter) term preferable. Most important is the diazo transfer reaction for the introduction of a diazo group into compounds containing a CH2 group bonded to two groups X and Y, of which at least one acidifies the CH2 group and dissociation of one of the protons converts the sp3C- into an sp2C-atom. Examples include groups such as COOR, CHO, COR, CONR2, COO~, NO2, SOR, SO2R, SO2OR, SO2NR2, POR2, PO(OR)2 and others* (R may be, in most cases, an alkyl or aryl residue). The classical transfer reagent is 4-toluenesulfonyl azide used in the presence of a base**. The mechanism is probably as depicted (in a simplified form) in Scheme (2-47). It will be discussed in Section 4.3. It must be emphasized that aryl azides are highly explosive; accidents have

base

\-

CH +

+

-

N=N—N—Ts

Y

X

Y—C —N 3 —Ts

(2-47)

H

C=N=N Y

+ Ts—NH

^

Ts—NH2

Ts: see (2-34)

* An exception is the nitrilo group. For 2-diazonitrile syntheses, the use of a benzothiazolium salt as transfer reagent is described later in this section. ** For a general method in CH2C12 with tertiary amines as base, see Meier et al. (1986). K2CO3 in acetonitrile also seems to be suitable (Koskinen and Mufioz, 1990).

50

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

been reported by Spencer (1981), and Rewicki and Tuchscherer (1972). Hazen et al. (1981) found out, however, that the isomeric mixture of dodecylbenzenesulfonyl azides exhibits a very low specific heat of decomposition and no impact sensitivity at the highest test level. This compound is currently used, on a commercial scale for the production of a diazo keto ester (see later in this Section). Under special conditions (addition of lithium amide, phase-transfer catalysis), compounds with apparently unactivated methylene groups (e. g., 5-methoxy-l-tetralone, Lombardo and Mander, 1980) or even with a methyl group at an arylcarbonyl group (Sugihara et al., 1987) undergo diazo transfer with arenesulfonyl azides. This is also the case for esters of 4-arylbut-3-enoic acid and related compounds (Davies et al., 1989, and references therein). Difficulties have been reported in the chromatographic separation of the desired product from excess 4-toluenesulfonyl azide and 4-toluenesulfonamide (Doyle et al., 1985; Hudlicky et al., 1985). Taber et al. (1986, 1988) found that methanesulfonyl azide (mesyl azide) is generally a superior reagent for diazo transfer*. The advantage of methanesulfonyl azide (mesyl azide) is that it is easily separated from the desired product by washing the organic phase (CH3CN or ether) with 10 % aqueous NaOH solution. Other transfer reagents are either more expensive or show similar disadvantages to those of 4-toluenesulfonyl azide (see Taber et al., 1986, references 5 and 6). Since 1985, Taber (1989) prefers mesyl azide to 4-toluenesulfonyl azide in all diazo transfers. Another, completely different azide was successfully employed by Mori et al. (1982) for the synthesis of (trimethylsilyl)diazomethane (2.104), namely commercially available diphenyl phosphazidate (DPPA, 2.103). The methylene group in (chloromethyl)trimethylsilane (2.102) is not sufficiently reactive. Therefore, the corresponding (carbanion-like) Grignard compound methyl(trimethylsilyl)magnesium chloride is formed first (2-48). A yield of 85 % of the diazo compound 2.104 is obtained with DPPA, whereas the yield is only 17 % with 4-toluenesulfonyl azide. This method is also used for an entry in Organic Syntheses (Shioiri et al., 1990). (Trimethylsilyl)diazomethane (2.104) was previously obtained by nitrosation of 7V(trimethylsilylmethyl)urea (Seyferth et al., 1972; Aoyama and Shioiri, 1981). (Silylsulfonyl)- and (phosphonyl)diazomethanes are, with a few exceptions, thermally stable and unexplosive derivatives of diazomethane. Reaction of the lithium salt

(CH3)3SiCH2CI

+M9

>

[(CH3)3SiCH2MgCl] 1

(2-48)

s—0)2P(0)N3

2.103

(CH3)3SiCH=N2 2.104

* For other arenesulfonyl azides used for diazo transfer, see Houben-Weyl (Klamann and Hagemann, 1990, p. 1054).

2.6 Diazo Transfer to Active Methylene Compounds

51

(2.105) of (trimethylsilyl)diazomethane (Aoyama et al., 1985 a, 1985 b) with chloroor bromoalkanes leads to homologs of diazomethane with a trimethylsilyl group in the a-position (2.106) (2-49, Aoyama and Shioiri, 1988). The synthesis and use of 2.106 as a reagent in organic chemistry have been reviewed by Anderson and Anderson (1991). (CH3)3SiC(Li)N2 + RCH2X

*~ RCH2C-Si(CH3)3

(2-49)

N2 2.105

2.106

For some diazo transfer reactions, a more lipophilic azide than mesyl or 4-toluenesulfonyl azide, is preferred. This is the case, for instance, in the Merck process for the synthesis of the /Mactam antibiotic thienamycin (Loracarbef), in which benzenesulfonyl azide with an dodecyl substitutent on the benzene ring is used (Salzmann et al., 1980; Reider and Grabowski, 1982; Bodurow et al., 1989; Reider, 1993). We will discuss the chemistry of the Merck process in Section 8.7. a-Methylene groups activated by only one carbonyl group react in most cases only if an aryl group is present in the other a-position (/?-aryl ketones). With such compounds, side products are obtained under certain conditions. Thus, phenylacetone (2.107) yields the expected a-diazo ketone 2.108, but also 2.109 as the product of a Wolff rearrangement (2-50) (Regitz, 1965 b; Hendrickson and Wolf, 1968). In the reaction of 1,2-diphenylethan-l-one (2.110) with 4-toluenesulfonyl azide 2-diazo-l,2-diphenylethan-l-one (2.111) is formed under alkaline conditions, whereas the rearranged 2,2-diphenyl-7V-tosylacetamide 2.112 (2-51) is isolated in an acidic medium (Regitz, 1964 b, 1965 b).

(2-50) NHTs 2.107

2.108

/C6H5

"

2.109

2.111

H5C6—CH2-CX X

2.110

(2-51)

O x

u^

NHTs

2.112

52

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

The diazo transfer method offers a route to terminal diazo derivatives, as a-diazo ketones are smoothly cleaved by treatment with alkali ethoxide. An Organic Syntheses procedure is described by Regitz et al. (1973) for obtaining tert-butyl diazoacetate (2.114). The diazo transfer from 4-toluenesulfonyl azide to tert-butyl acetoacetate (2.113) in anhydrous acetonitrile and one equivalent of triethylamine yields tert-butyl a-diazoacetate (94-98%) after cleavage of the central C-C bond of the primarily formed a-diazo ketone with sodium methoxide (2-52). With ethyl acetoacetate instead of the tert-butyl ester 2.113, the yield is, however, only 65% (Regitz, 1965 b). H3C XC

ox

+TsN 3

— CH2—COOC(CH3)3

H3C

COOC(CH3)3 -

~

2.113 NaOCH3/CH3OH - CH3COOH

COOC(CH3)3 HC

\ 2.114

Another method was found by Ok et al. (1988) for diazoacetates involving esters derived from valuable or sensitive alcohols (2-53). The corresponding alcohol (2.115) is esterified with glyoxalic acid 2,4,6-triisopropylbenzenesulfonyl hydrazone (2.116, TIPPS), using dicyclohexylcarbodiimide (DCC) for condensation, followed by the addition of 4-(dimethylamino)pyridine (4-DMAP). Q

H

4-SCVKr _pc^ 2.115

±PMAP^

^ ^^ ^

(2_53)

2.116

This cleavage of /?-carbonyl groups is particularly facile if the a-position contains only one H-atom. The order of preference for cleavage is CHO >COR>COOR (Hendrickson and Wolf, 1968). With an aldehyde function as leaving group, this modification is called deformylating diazo transfer (Regitz, 1967). This reaction has found wide use in cases of a-methylene ketones without another neighboring activating group. For such starting materials, the aldehyde group is first introduced by a Claisen condensation, followed by the deformylating diazo transfer (2-54). The base mentioned in (2-54) is either an alkali methoxide in diethyl ether, pulverized sodium in diethyl ether, or triethylamine in dichloromethane or

2.6 Diazo Transfer to Active Methylene Compounds R'— C — CH2— R" II O

HCQQR

»

ROH

-

R'— c—CH—R" +TsN3-bas% II I //° O CHO - HC

R/_C_C_R-

II O

53 (2.54)

II N2

NH—Ts

R' = R"= H,alkyl

acetonitrile (Regitz and Menz, 1968). The latter method is particularly useful for the synthesis of cyclic (2.117, n = 5-12, Regitz and Riiter, 1968; see also Taber et al., 1986; Askani and Taber, 1991) and bicyclic ketones such as trans-5-diazobicyclo[6.1.0]nonan-4-one (2.118, Wiberg and de Meijere, 1969) and 3-diazol-methyl-bicyclo[2.2.1]heptan-2-one (2.119, Gibson and Erman, 1966). In Organic Syntheses, the preparation of 2-diazocyclohexanone by deformylating diazo transfer of 2-(hydroxymethyl)cyclohexanone is described (Regitz et al., 1988). Cyclic a-diazo ketones have also been synthesized by diazo transfer with phase-transfer catalysis (Lombardo and Mander, 1980).

(H2C)n_2

tf 2.117

2.118

As the formylation of a methyl ketone is usually highly selective for the methyl group, such formylated methyl ketones easily give the a-diazomethyl ketones by addition of a sulfonyl azide (LeBlanc and Sheridan, 1988). Instead of the replacement of a formyl group a trifluoroacetyl group can also be used (Doyle et al., 1985; Danheiser et al., 1990a). The synthesis follows the reaction sequence (2-55). Provided that the necessary reagents are available, the method has the advantage of higher yields in the synthesis of vinyl- and aryl-a-diazo ketones. Danheiser's process has often been used since 1990, e.g., for the first synthesis of

N

Li+ / THF

F3C—CO—O—CH2—CF3, -78°C

H3C—S02—N3/N(C2H5)3

FT

54

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

enantiomerically pure TV-protected /?-amino-a-keto esters from a-amino acids and dipeptides by McKervey's group (Darkins et al, 1994; see Sect. 9.4). Excellent yields of diazo compounds can be achieved, if both neighboring Catoms of the reacting methylene group are carbonyl functions, e.g., 1,3-diketones, /?-keto esters (as in 2-52), dialkyl malonates, etc. (Regitz and Liedhegener, 1966; Hendrickson and Wolf, 1968; for more recent work see Popik et al., 1991, and Ye and McKervey, 1994). For these compounds, synthesis by diazo transfer has almost entirely replaced the synthesis by diazotization of amines. The diazo transfer from 4-acetaminobenzenesulfonyl azide to ethyl acetoacetate yielding ethyl diazoacetoacetate is the subject of an Organic Syntheses procedure (Davies et al., 1992c). Diazo groups located between two carbonyl groups are relatively strong electrophiles. The starting 1,3-dicarbonyl compounds, on the other hand, have a nucleophilic C-atom in the 2-position, as revealed by their keto-enol equilibria and the acidity of the methylene group. If they are used in excess over 4-toluenesulfonyl azide, the 2-diazo-l,3-dioxo compound formed may react with the excess of the 1,3-dicarbonyl compound. In this two-step reaction an azo compound is, therefore, the final product. In Scheme 2-56, this sequence is shown for 5,5-dimethylcyclohexane-l,3-dione (2.120) with the primary product 2-diazo-5,5-dimethylcyclohexane-l,3-dione (2.121), followed by the formation of the corresponding 2,2'-azobis(l,3-dioxo) compound. The latter is likely to be present as an H-bonded dienol (2.122). This type of reaction was discovered by Regitz and Stadler (1964, 1965) and called an 'azo group transfer'. In our opinion, this term is not correct, as the overall sequence is a diazo transfer reaction followed by an azo coupling reaction.

O

(2-56)

There are two reactive methylene groups in a,y,e-trioxo compounds of the type 2.123. With one equivalent of diazo-transfer reagent, 2//-3,4-dihydropyrazol-4-one 2.125 is obtained, not the monodiazo compound 2.124 (Regitz and Geelhaar, 1968). This compound is obviously the product of an intramolecular azo coupling reaction (2-57). Two equivalents of 4-toluenesulfonylazide, however, lead to the/?,£-bis(diazo)a,y,e-trioxo compound 2.126. An interesting problem is the question whether the pyrazolone 2.125 is an intermediate in the formation of the bis(diazo) compound 2.126 or if 2.126 is formed directly from the monodiazo compound 2.124. This question has not been examined by the authors mentioned. Regitz et al. (1969) found an analogous reaction pattern with a compound, which contains four activated methylene groups (2-58). Very recently, Sezer and Anag (1994) found that 2-azido-l-ethylpyridinium tetrafluoroborate is a suitable diazo transfer reagent for the introduction of diazo groups

2.6 Diazo Transfer to Active Methylene Compounds

55

N(C2H5)3

2.123 I TsN3/CI-^CN I N(C2H5)3

.C— C — C

'

R'

,C—C—C

2.126

2.125

C Hp

0

0

O

II

C Hp

/C6H5 Ov

% U

(2-58) 2molTsN3

O

N2 O

N2

56

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

into acylacetaldehydes (RCO - CH2 - CHO). The reaction proceeds partially without deformylation to yield 16 new a-diazo-/?-oxoaldehydes (RCO - CN2 - CHO), in part together with diazomethyl ketones (RCO — CHN2). Polymer-bound arylsulfonyl azides have been tested as diazo transfer reagents (Roush et al., 1974; Diirr et al, 1981). Yields with diethyl malonate and acetylacetone are slightly lower than those with 4-toluenesulfonyl azide. In contrast to these compounds with two neighboring activating groups, yields with monoactivated methylenes (ethyl propionate and cyclohexanone) are much lower. This method is therefore, not recommended in the described form. Nevertheless, phase-transfer catalysis is an advantageous method for diazo transfer reactions, as mentioned previously for cyclic a-diazo ketones (Lombardo and Mander, 1980) and shown also by Starks (1971) and Ledon (1974). Di(tert-butyl) malonate reacts with 4-toluenesulfonyl azide in methylene chloride and in the presence of a small amount (2 mol-%) of methyl(trioctyl)ammonium chloride as phase-transfer catalyst. After workup with aqueous NaOH di(tert-butyl) diazomalonate is obtained in 59-63% yield, whereas without phase-transfer catalysis the yield is only 47 % after a reaction time of 4 weeks! The procedure is described in Organic Syntheses (Ledon, 1988). Diazo transfer to malonates and vinylogous malonates has also been investigated by Davies et al. (1985). Methylene compounds with two neighboring sulfone groups can also be used for diazo transfer reactions as shown in 1964 by Klages and Bott. They obtained diazobis(ethylsulfonyl)methane (2.127) and diazobis[(diethylamino)sulfonyl)]methane (2.128) in aqueous ethanol and NaOH at - 5 °C and in ether with methyllithium at room temperature, respectively. In a similar way, methylene compounds activated by a sulfone and a carbonyl group, yield diazo derivatives, e. g., 1-diazol-(4/-toluene)sulfonyl propan-2-one (2.129, van Leusen et al., 1965), 2-diazo-2-(methylsulfonyl)-2-phenylethan-l-one (2.130, Illger et al., 1972), l-diazo-l-[(4'-nitrophenyl)sulfonyl)]propan-2-one (2.131, Hodson et al., 1968), and other a-diazo/?-oxo-/?'-sulfonyl compounds (Monteiro, 1987 b) and similar diazoalkanes (van Leusen and Strating, 1988). H5C2— S02- C — S02-C2H5

(H5C2)2N—S02- C — SO2— N(C2H5)2

N2

N2

2.127

2.128

2.6 Diazo Transfer to Active Methylene Compounds

57

As discussed above for diazo transfer reactions of 1,3-diones (1.120), a-diazo/?-oxo-/?'-sulfonyl compounds are relatively strong electrophiles and can undergo azo-coupling reactions with an excess of the methylene substrate. Thus, Regitz (1965 a) obtained only the dipotassium salt of the azo compound 2.133 in the reaction of 3-oxo-2,3-dihydrobenzothiophene-l,l-dioxide (2.132) with 4-toluenesulfonyl azide, even when working without an excess of 2.132 (2-59). After acidification and heating in ethyleneglycol, dimethylformamide, or dimethylsulfoxide, the azo compound was cleaved again (probably via its hydrazone tautomer 2.134), and 2-diazo-2,3-dihydrobenzothiophen-3-oxo-l,l-dioxide (2.135) was obtained.

TsN 3 /C 2 H 5 OH/ KOH

(2-59)

2.135

Methylene compounds activated by cyano or nitro groups (e. g., malonodinitrile, see Keller et al., 1975, and Stadler et al., 1975) exhibit a complex product pattern in classical diazo transfer reactions with tosyl azide. It seems, however, that benzothiazolium salts (Balli et al., 1978a), or such salts in combination with NaN3 in CH3OH-H2O (Kolobov et al., 1987) can be used for the synthesis of 2-diazonitriles. a-Diazophosphine oxides and -phosphonates can be obtained in a similar way by diazo transfer reactions, although these groups do not very particularly activate the methylene group. Yields are generally higher, if in addition to the activating ability

58

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

of the P = O group, a carbonyl group is present as a second substituent at the methylene group to be substituted by the diazo group. Comparison of the yields of the three diazophosphonates, diazobenzyl diethyl phosphonate (2.139, Regitz et al., 1968), tetraethyl diazomethylene(bisphosphonate) (2.137, Regitz et al., 1968) and (diazo) (dimethoxy)phosphorylacetic acid dimethylamide (2.138, Bartlett and Long, 1977), demonstrated this effect very well. The same effect is also found when the yield of diazobenzyl-diphenylphosphine oxide (2.136, Regitz et al., 1968; Regitz and Anschiitz, 1969) is compared with that of diazophenylacyl diphenylphosphine oxide (2.140, Petzold and Henning, 1967; Regitz et al., 1968; Regitz and Anschiitz, 1969; Corbel et al., 1987). C6H5

H5C20

H5C6-P-C-C6H5

O

OC2H5

OCH3

H5C20-P-C-P-OC2H5

N2

O

2.1 36 (24%)

H3CO-P-C-C-N(CH3)2

N2 O

O

2.1 37 (35%)

N2 O

2.1 38 (70%)

C6H5 H5C20-P-C-C6H5

O

H5C6-P-C-C-C6H5

N2

O

2.1 39 (30%)

N2 O

2.1 40 (65-1 00%)

Bartlett and Long (1977) were able to synthesize a-diazophosphonates (as dianions, 2.143) by transesterification of the corresponding dimethyl a-diazophosphonates (2.141) with bromo-(trimethyl)silane, furnishing the extremely moisture-sensitive bis(trimethylsilyl) esters (2.142), which were hydrolyzed under very mild (pH 8-9) aqueous conditions. The half-life for decomposition of a-diazobenzylphosphate dianion is less than 1 min in aqueous solution at pH 8.0, although it can be prolonged by appropriate choice of the buffer (2-60). As mentioned earlier in this section (Schemes 2-56 and 2-59), an azo coupling reaction may follow the diazo transfer to a reactive methylene compound. The mechanistic rationale of the subsequent azo coupling is the fact that, in general,

X

P03(CH3)2

X^

(j

/P03[Si(CH3)3]2

.

X^

.

fi

N2

fj

N2

2.141

N2

2.142

0

II X = (H C ) N — S—, 5

22

O

/P032-

2.143

0

O

II II (H C) N—C— , or (2-C H ) N —C — 3

2

3

72

(2*0)

2.6 Diazo Transfer to Active Methylene Compounds

59

diazo transfer reactions must be carried out either in excess of the methylene compound or (and) in slightly alkaline solution in order to shift the equilibrium from the methylene compound to its carbanion. The latter is, however, also the reactive substrate in the azo coupling reaction. This diffculty can be avoided by using a more electrophilic diazo transfer reagent than a sulfonyl azide. Such a reagent is an azidinium salt, in particular the 3-ethylbenzothiazol-2-azidinium tetrafluoroborate (2.144). The chemistry of azidinium salts has been intensively investigated by Balli (Balli, 1961; Balli and Miiller, 1964; Balli and Gipp, 1966; Balli and Low, 1966; Balli and Felder, 1978; Balli et al., 1978 a-b). A characteristic example is the introduction of a diazo group into barbituric acid (2-61): with the azidinium salt 2.144 in 2 M sulfuric acid at 50 °C 5-diazobarbituric acid (2.145) is formed in 84% yield (Balli et al., 1978b), whereas diazo transfer with 4-toluenesulfonyl azide in aqueous ethanol and KOH at 20 °C results in a much lower yield (61%, Regitz, 1964 c). The same azidinium salt was used for the first syntheses of nitro- and cyanodiazoalkanes (2.146, 2.147, Balli and Miiller, 1964; Balli and Low, 1966; Balli et al., 1978a). The series of cyanodiazo ketones (2.147) demonstrates, however, that yields of diazo transfer reactions with an azidinium salt may vary considerably. Diazo transfer products were not obtained with nitroalkanes lacking a carbonyl group in the other neighboring position of the reacting C-atom (e. g., with nitromethane, nitroacetonitrile, and phenylnitromethane).

-N+ BF4

(2-61) 2.144

2.145

N2=CV

NC—C —C —R

H, ft

2.146 R = OCH3 (18%) C6H5 (21%)

2.147 R = CH3 (51%) C6H5 (88%) OC2H5 (73%) NH2 (12%)

60

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

l,3,5-Tris(diazo)cyclohexane-2,4,6-trione (2.148) can be obtained in 96% yield by diazo transfer from 2-azido-3-ethyl-benzothiazolium tetrafluoroborate to benzene-l,3,5-triol (phloroglucin, Balli et al., 1978 b). Analogously, the five-membered ring compound 2,5-bis(diazo)-cyclopentane-l,3,4-trione (2.149) and 3,5-bis(diazo)pyran-2,4,6-trione (2.150) were synthesized (Maier et al., 1990). They are interesting for the synthesis of dioxides of carbon OC^C^O, n = 1, 2, or 3 (Maier et al., 1988, 1990, 1991; Holland et al., 1988).

O

2.150

a-Cyano-a-(phenylsulfonyl)diazomethane [ = diazo(phenylsulfonyl)acetonitrile, Balli et al., 1978a] and a-diazophosphonium salts (2.152, Regitz et al., 1981 a) can also be obtained with the azidinium salt 2.144 as transfer reagent. The yields of 2.152 are strongly dependent on the type of the group R (high yields with R = alkyl and alkyloxy) and the solvent (high yields in benzene and ethanol). With aryl residues as R and in methylene chloride the yields of the corresponding a-diazophosphonium salts are low, and significant amounts of (bromomethyl)triphenylphosphonium tetrafluoroborate (2.151) are formed (2-62). Consecutive azo coupling is, however, also possible if azidinium salts are used as transfer reagents, and heteroaromatic enols, aromatic or heteroaromatic amines as substrates (Balli and Gipp, 1966; Balli and Felder, 1978; Balli et al., 1994). An example is the reaction of 5-methyl-2-phenyl-3,4-dihydropyrazol-3-one (2.153) with the azidinium salt 2.144 (2-63). At pH 3-4 the 4-diazo derivative 2.154 is formed, but O (HsCeJgP-CH,—C-R + |

||

/-N3

BF4

X~ C2H5

.. (2-62)

(H5C6)3P-CH2Br BF42.151

(H5C6)3PX R ^C~C^

BF4-

r/

^o

2.152

2.6 Diazo Transfer to Active Methylene Compounds

H3C 2 144

C2H5

'

61

Ns

pH 3.0-4.0

(2-63)

pH 5.0 - 8.0

C6H5

2.155

at pH 5-8, the azo compound 2.155 is also found. 4-Diazo-5-methyl-2-phenyl-3,4-dihydropyrazol-3-one (2.154) has, of course, the ambient character of a diazonium-enolate zwitterion, and the azo product 2.155 is in equilibrium with the tautomeric hydrazone. This reaction may, therefore, also be placed in Section 2.6 of the volume on aromatic diazo compounds (Zollinger, 1994). (Azido)(chloromethylidene)dimethylammonium chloride (2.156), as a diazotransfer reagent, is comparable to the benzothiazolazidinium salt 2.144. The former also reacts in neutral or acidic solution (Kokel and Viehe, 1980). The yield of 2-diazo-5,5-dimethylcyclohexane-l,3-dione (2.121, 78-80%) is comparable to that with the benzthiazolazidinium ion 2.144 (Balli et al., 1978a)*. In the azido-ammonium ion 2.156, the reactivity of the azido group is increased by the vinylogous position of the ammonium group, in a similar way to that in the thiazolium ion 2.144. The electron-withdrawing effect of the two vinylogous cyano

H3C

N3

cr ^

N=C H3C

H3C

^

Cl

N C

/N-N2+

cr

/ - \ H3C

Cl

2.156

* It may be that the mixture of l-ethyl-2-chloropyridinium tetrafluoroborate and NaN3, recommended by Monteiro (1987 a) for diazo transfer to activated methylene compounds is essentially based on the primary formation of l-ethyl-2-azidopyridinium ions as transfer reagent.

62

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

groups is obviously the source of the diazo transfer capability of 2-azido-2-phenyl1,1-dicyanoethene (2.157), and not the formal charge. This compound was proposed for this purpose by Arnold and Regitz (1980). Another diazo transfer reagent, for which a high reactivity is claimed, using only a catalytic amount of base, is (azido) tris(diethylamino)phosphonium bromide (2.158; McGuiness and Shechter, 1990).

NC

N3 [(C2H5)2N]3P+ Br

X C=C

NC

C6H5

2.157

2.158

As mentioned at the beginning of this section, diazo compounds may act as diazo transfer reagents. Nevertheless, few cases are known (see however, the addition of diazomethane to alkynes in Sect. 2.8). A lucid example within the framework of this section is the formation of ethyl diazoacetate (2.161) and 4-nitroaniline from the triazene 2.160, which is the 7V-azo-coupling product of the aromatic diazonium ion 2.159 and ethyl aminoacetate (Baumgartner, 1967). For synthetic purposes, the method is hardly of interest due to low and variable yields (30-66%). McGarrity (1974) reported that the diazo transfer reaction via the triazene 2.160 in (2-64) gives a quantitative yield if catalyzed by acid and not by base. H5C2OOC-CH2—NH2

+

HP nor PH M H5C2OOC — CH2— N X

*•

N—

2.160

2.159 H5C2OOC—CH =

2.161

More recently, this reaction was re-investigated in greater detail by Vaughan's group (Daniels et al., 1977; Raines et al., 1981; Baines et al., 1983). The triazene 2.160 was degraded with concentrated HC1 in ethanol at ambient temperature for 36 h or with triethylamine in boiling ethanol for one hour. 4-Nitroaniline was isolated in 60 and 90% yield, respectively, but no diazoacetate was found. In chloroform after 24 h at room temperature, ethyl diazoacetate was detectable by *H NMR. These authors (Baines et al., 1983) found, however, that five triazenes of type 2.160 with electron-withdrawing substituents in the 4-position formed l-aryl-1,2,3l/f-triazol-5-ols (2.162) in ethanol and KOH. The NMR spectra show that they are the major component in the keto-enol equilibrium (2-65). These compounds yield

2.7 Diazo Transfer to Alkenes

Ar—N X %

Ar—N X ^N

^

63

(2_65)

O

HO 2.162

the diazoacetamides 2.163, by refluxing in absolute ethanol, obviously by cleavage of the N(1)-N(2) bond. A similar example with a relatively electrophilic diazoalkane is the diazo transfer (2-66) from ethyl diazonitroacetate (2.164) to 5,5-dimethylcyclohexane-l,3-dione (2.120) described by Schollkopf et al. (1969). Ar—NH—C—CH=N 2 II O 2.163

(2-66)

O XCOOC2H5 N2=C V

C2H5oH/N(C2H5)3

^

H3C / ( X )=N2 H3C Y_^

COOC2H5 + H2C

O 2.164

2.121

2.7 Diazo Transfer to Alkenes As mentioned already in Section 2.6, it is somewhat arbitrary to discuss diazo transfer reactions to alkenes in isolation from those to activated methylene compounds. The most important activation in methylene compounds is that of a neighboring carbonyl group and, as a consequence, the active methylene compound is in equilibrium with the corresponding enol, i.e., with an alkene: as established by the systematic work of Huisgen (review: Huisgen, 1984), typical diazo transfers involve 1,3-dipolar cycloaddition of a 1,3-dipole (azides) to a multiple-bond system, the dienophile (see Chapt. 6). In diazo transfer, this dienophile is an alkene or an alkyne, and the primary product is a A2-l,2,3-triazoline or a A2-l,2,3-triazole,

64

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

respectively*. This 1,3-dipolar cycloaddition was discovered by Michael (1893), when he found diethyl l-phenyl-l,2,3-triazole-4,5-dicarboxylate by reaction of phenyl azide with diethyl acetylenedicarboxylate. Today, it is the most important synthetic route to 1,2,3-triazoles and A2-triazolines (reviews: Gilchrist and Gymer, 1974; Finley, 1980). In the subsequent part of the diazo transfer one or two bonds of these fivemembered heterocycles is (are) cleaved, leading to diazo compounds. In Scheme 2-67 various pathways from an alkene (2.166) and an azide (2.165) through A2-l,2,3-triazolines (2.167 or 2.168) to diazoalkanes are shown. Here X1, X2, Y1, and Y2 are either hydrogen, alkyl, aryl, or heteroatom substituents (e.g., OH, NR2, etc.), and R refers to an alkyl, aryl, or arylsulfonyl group.

(2-67)

R—NH2

Some substituents may be charged (e. g., O ), but, for convenience, charge is not indicated in the scheme. Competitive and consecutive reactions, which may be dominant in many cases (e. g., dediazoniations), are also not included. The scheme is not intended for mechanistic considerations. In particular, the formation of the triazoline may be a one- or a two-step reaction (see Sect. 6.3). It should be taken into account that unsymmetrically substituted alkenes do not add to azides regiospecifically, i. e., that the two orientationally isomeric triazolines * Greek capital delta (A) with a superscript is used to denote a double bond. In line with IUPAC (1979, p. 54), we use A only exceptionally, e.g., 2.167 is a 4,5-dihydro-A2-l,2,3-triazole.

2.7 Diazo Transfer to Alkenes

65

2.167 and 2.168 are formed in a certain ratio. Products of ring opening, which are analogous to pathways A, B, and C of triazoline 2.168, are, of course, also possible for triazoline 2.167 (A', B', C'). Although their structures with respect to the substituents are different from the products of triazoline 2.168, the mechanisms of ring opening remain the same. Furthermore, (E)- and (Z)-substituted alkenes will, depending on the actual mechanism of cycloaddition, yield stereochemically different triazolines or products in equilibrium. These stereochemical considerations are important for the elucidation of the mechanism of 1,3-dipolar cycloadditions involving azides as 1,3-dipoles (see Sect. 6.3 and the reviews by Huisgen, 1984, and Lwowski, 1984). The main purpose of including Scheme 2-67 in this section is the fact that the intermediate triazolines can form diazoalkanes by three different ways of ring-opening, as shown in formula 2.168 by A, B, and C. In pathway A, the two bonds to the N-atom (N1) of the azide are cleaved. The diazoalkane syntheses discussed in Section 2.6 proceed by this process. Pathway B is closely related to A; if the C(a)-N1 bond is sufficiently strong, the amine residue R —N~ will be protonated and it will remain within the rest of the diazoalkane. If there is no H-atom at C(/?), no diazoalkane can be formed. The intermediate alkyldiazonium zwitterion 2.169 will lose N2, and the carbocation will be solvolyzed or it will form rearranged products that are of no immediate interest in the context of the present section. With very few exceptions, we will discuss the chemistry of azide additions only for reactions leading to diazo compounds. We will review first the influence of the organic residue R of the azides used for the reactions in Scheme 2-67. Fusco et al. (1961 a, 1961 b, 1962) studied the formation of triazolines by cycloaddition of enamines and aromatic azides (2-68). 5-Aminox

Ar—N 3

+

\

R2N

/*2

C=C

X

H

X1

/N ^N K XNX 2 170

'

(2-68)

xi=H(etc.)

'- RjNH

X1

X2

W /

2.171

\

2.172

66

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

l-aryl-4,5-dihydro-l//-l,2,3-triazoles (2.170) are obtained easily and in good yield. With acid or by heating, l-aryl-l,2,3-triazoles (2.171) and amines ar formed from these dihydrotriazoles. If X1 = H and, in some other cases, the five-membered ring is opened, N2 and an amidine (2.172) are formed. The ring opening obviously corresponds to the formation of the diazonium zwitterion 2.169 in Scheme 2-67, which decomposes by dediazoniation and rearrangement of Y1 in the carbocation. Later, Fusco et al. (1963) used toluenesulfonyl azide for the addition to enamines. The expected dihydrotriazole was not observed, but diazomethane and an amidine were obtained, as shown for the reaction with a-(7V-methylanilino)styrene (2.173) in (2-69). This route obviously corresponds to pathway C in Scheme 2-67. Dediazoniation products were also observed with toluenesulfonyl azide (Bianchetti et al., 1965; Huisgen et al., 1965). C6H5

(2-69) H5C6-N

C6H5

C II N

+

CH2 II N2

Ts/

Indole and its derivatives may be considered as enamines. Their reaction products with azides demonstrate, however, that in most cases complex dediazoniation products are formed rather than diazoalkanes. Their structure was elucidated mainly by Bailey's group (review: Peach and Bailey, 1979). Under phase transfer conditions 2-aryl- or 2-heteroaryl-substituted indoles are converted into the corresponding 3-diazo-3//-indoles by 4-toluenesulfonyl azide (2-70) (Gonzalez and Galvez, 1981).

TsN3 / NaOH / H2O benzene / TEBCI (2-70)

R = C6H5, a-pyridyl, a-thiophenyl

X = H, Cl, or F TEBCI = (triethyl)benzylammonium chloride

2.7 Diazo Transfer to Alkenes

61

The influence of the organic moiety of the azide in cylcoadditions to enol ethers is analogous to that in additions to enamines. Comparative cycloadditions of 4-(methoxyphenyl)-, 4-(nitrophenyl)-, and 4-toluene-sulfonyl azide to 2,3-dihydrofuran show that the rate of cycloaddition increases dramatically in the sequence mentioned (Huisgen et al., 1965). Yet, the dihydrotriazoles formed (2.174) are stable only in the case of the first aryl azide mentioned. With 4-toluenesulfonyl azide the product of dediazoniation (2.175) was the only compound detected (96% yield). Analogous results were obtained with 3,4-dihydro-2//-pyran.

o

HC—CH


/

Ts-N// 2.174

2.175

The results discussed above clearly demonstrated that the cleavage of the dihydrotriazole ring to diazoalkane products following Scheme 2-67 is facilitated most by 4-toluenesulfonyl azide, although, in some cases, diazoalkanes can also be obtained with other aryl azides. Unfortunately, no study has been conducted comparing reactivity, products, and the yields of reactions with methanesulfonyl azide. This transfer reagent was recommended by Taber et al. (1986, see Sect. 2.6) as a superior reagent to 4-toluenesulfonyl azide. The much lower reactivity of the phosphoryl azides 2.177 in Scheme 2-71 is probably the reason that diazomethane and phosphorylated imino ethers are formed in 50-80% yield with isopropyloxyethene (2.176) (Berlin and Khayat, 1966). A dihydrotriazole intermediate was not observed. R = CH-OCH(CH3)2 + R-P-Ns U

2.176

2.177

OCH(CH3)2 ^

H2C = N2 +

HC^ R N-P-R

O

R = C2H5O,C4H9O, C6H5

As shown by the preceeding example, alkenes with an electron donor substituent on one of the alkene C-atoms form dihydrotriazoles with that substituent in the 5-position. Many additional examples, particularly with enamines, can be found in the literature (e.g., Dalla Croce and Stradi, 1977). Alkenes with an electron-acceptor substituent generally add azides in the opposite manner, i. e., the substituent will be in the 4-position. Examples of such cycloadditions have been described by Huisgen et al. (1966b). These authors synthesized alkyl 2-diazo-3-(phenylamino)propionates

68

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

(2.179) by base-catalysed ring opening of alkyl 4,5-dihydro-l-phenyl-l//-l,2,3-triazole-4-carboxylates (2.178), which were obtained from alkyl acrylates and phenyl azide (2-72). As the diazo compound 2.179 is a 1,3-dipole, it undergoes a second cycloaddition with excess acrylate to give the dihydropyrazole 2.180. .COOR H2C=CK

+

H5C6—N3

COOR H2C —CH \

HA

•"V 2.178

•Et a N

COOR H2C-CX

""""" ROOC

.NH N2 H5C/ 2.179

+

.COOR H

^=CH/

N

/

(2.72)

H2C /Nl~ H5C6 COOR H2C— C ROOC

/ / ^ NH 2.180

Acrylonitrile adds analogously to phenyl azide giving 4,5-dihydro-l-phenyl-l/fl,2,3-triazol-4-carbonitrile (2.181; Gurvich and Terentev, 1953). This compound can also be cleaved with triethylamine to form 2-diazo-3-anilinopropionitrile (2.182, Huisgen et al., 1966 b). The ring opening is much faster than that of the alkyl carboxylate 2.178 in (2-72), but it is interesting that it does not lead to completion, but to an equilibrium mixture of 29% diazoalkene 2.182 and 11% triazoline 2.181 (2-73). The regiospecificity of addition of substituted alkenes to azides is not as absolute as the preceeding examples with enamines, enol ethers, and acceptor-substituted alkenes may imply: in all those cases the reverse addition product was not detected. This does not mean that it cannot be formed. Ouali et al. (1980) found cases in which both isomers were indeed obtained. Methyl acrylates with an acceptor substituent at

2.7 Diazo Transfer to Alkenes

1CN

"H

XNX X

XN X

69

CN

-. TiT

NH N2

Ar

N

2.181

2.182

each of the two alkene C-atoms (2.183) can form the corresponding diazoalkane 2.186 for obvious reasons only if there is an H-atom in the 4-position of the intermediate dihydrotriazole 2.185. Neither this compound (only its isomer 2.184) nor the diazoalkane 2.186 was detected when benzyl azide (R = C6H5CH2 —) was used as reagent. With methyl azide (R = CH 3 -) only traces, with phenyl azide (R = C 6 H 5 -) considerable yields, of the diazoalkanes 2.186 were achieved (Table 2-2). With other substituents in the methacrylate, the reactions followed pathway A when methyl azide or phenyl azide was used as transfer reagent (2-74). It is clear from Scheme 2-67 that substituted ethenes of the type XYC = CX'Yf (X * Y; X' 4= Y') yield dihydrotriazoles 2.167 and 2.168 with chiral C-atoms C(a) and C(/?). If the formation of these dihydrotriazoles is a concerted reaction only one stereoisomer of each of the two dihydrotriazoles is expected. If the heterocyclic ring is formed in two steps, however, racemic mixtures result. The stereochemistry of this cyclization reaction is, therefore, an important mechanistic tool. It will be discussed in Section 6.3 in the general context of the mechanism of 1,3-dipolar cycloadditions. Here we will mention first of all Huisgen and Szeimies' classical investigation (1965). They found that the reaction (2-75) of 4-nitrophenyl azide with (£>propenyl propyl ether (2.187) furnished only the dihydrotriazole 2.189. The (Z)-isomer (2.188) gave the (Z)-adduct 2.190 (10%) besides the propionimidate 2.191 (19%). In artificial mixtures of the stereoisomers 2.187 and 2.188, 3 % of the minor component was detected. Therefore, the stereospecificity is greater than 97%. At the same time Scheiner (1965) prepared dihydrotriazoles by the addition of phenyl azide to (Z)- and to (^-methylstyrene and obtained in each of the two cases a different, but isomeric, dihydrotriazole without the other isomer. As the yields of these triazoles were low

Table 2-2. Yields of cycloaddition of azides R-N3 to substituted methyl acrylates (Scheme 2-74).

R

X

Y

CH3

CN

COOCH3

CH3

COCeft

COOCH3

CH3

COCH3

COOCH3

Oft

COOCH3

COOCH3

Oft

COQft

COOCH3

a

) Traces of diazoalkane 2.186.

Yield of Diazoalkane 2.186 a

) ) a ) 50% 60% a

70

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

(2.74)

2.184

*-*

H3coocr R

2.186

wX

J f

^

C-CH3

C-H H3C 2.188

H 2.187 +

> -^ N0 2 C 6H4N 3

4-N02C6H4N3

(2-75)

4-N02C6H4— N )

(-.CH3

H-)

(--H CH3

2.189

2.190

2.191

(22% and 24%, respectively), and as no artificial mixtures were investigated, conclusions regarding the stereospecificity are, however, hardly justified. Subsequently, higher stereospecificities were found for other 1,3-dipolar cycloadditions to alkenes (e.g., 99.997% for dihydropyrazoles formed from diazomethane and alkenes, Bihlmaier et al., 1978, see also Huisgen, 1984, p. 61-76). Intramolecular 1,3-dipolar cycloadditions of (2Z,4Z)-, (2^4^)-, and (2£,4Z)-6azidohexa-2,4-dienoates (2.192) are also stereospecific, as investigated by Sundberg and Pearce (1982). In Scheme (2-76) products are shown for the reaction

2.7 Diazo Transfer to Alkenes

71

of the (Z,Z)-isomer (R = R' = CH3): the primary product 3a,6-dihydro-3//-pyrrolo[l,2-c][l,2,3]triazole, not characterized) is converted to the a-diazo-2,5-dihydropyrrole-2-acetate 2.193, which is the kinetically determined product. The final (thermodynamically determined) product is the 2-substituted pyrrole 2.194.

(2-76)

Rr C. /COOR

H

N2 2.193

The diazo transfer to ketones has already been discussed in Section 2.6. It is likely that the latter react through the corresponding enol or enolate. Therefore, their reaction with azides may be a 1,3-dipolar cycloaddition, but also a Dimroth reaction (1902), i.e., attack of the terminal azide N-atom on the carbanion, followed by cyclization (see Lwowski, 1984, p. 606). Indeed, there are many reports on diazo transfers to ketones in which dihydrotriazoles have been observed as metastable intermediates or final products. Olsen and Petersen (1973 a, 1973 b, see also Olsen, 1973) found both diastereomeric dihydrotriazoles in reactions of aryl and alkyl azides with a large number of ketones. Does this indicate that they are therefore not stereospecific cycloadditions? The answer is "not unambigously": These authors found that in the formation of l-benzyl-4,5-dihydro-4,5-dimethyl-l//-l,2,3-triazol-5ol (2.195, R = R' = CH3, R" = CH2C6H5) only one isomer was detected by *H NMR spectroscopy if the spectrum was recorded immediately after dissolution in CHC13. Yet, a mixture of both isomers was found after a few minutes. It is reasonable to assume that this equilibration proceeds through the triazene 2.196. No ring opening of these dihydrotriazoles to the diazo compound, as indicated in Scheme 2-67, was found in these reactions. All the same, we have included Olsen's work here, as it is important in the context of the mechanism of cycloadditions as an apparent contrast to Huisgen's investigations. Diazo transfer reactions to enamines are very important for the synthesis of diazoaldehydes. They can be obtained in good yields from formyl enamines (2.198) and 4-toluenesulfonyl azide (2-78), e.g., a-diazobutyraldehyde (2.199, R" = C2H5) was synthesized for the first time by this route from a-ethyl-/?-(dimethylamino)acrolein and a-diazoacetaldehyde (2.199, R" = H) in an analogous fashion (Kucera and Arnold, 1966; Arnold 1967; Kucera et al., 1970; Menicaglia et al., 1987). It is probable that the corresponding dihydrotriazole is the metastable primary intermediate

72

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

»_

R-CH2-<"

H

B

-OH/

t**-0"

»

-

*

°H

H p

2.195

2.197

Y

R

(2-77)

P R' N NH— R"

2.196

that is cleaved via pathway C in Scheme 2-67. Kucera and Arnold (1967) made the observation that the yield of diazoacetaldehyde is good (71-74%) only if the substituents R and R' do not strongly increase the basicity of the amino group. The pATa of the corresponding amine should be in the range 4.6-5.3, e.g., with R = H or CH3, R' = C6H5, but not R = R' = alkyl (pATa = 10.7-11.1), R,R' = morpholino (p#a = 8.3), or R = R' = C6H5 (p^a = 0.8). Methanesulfonyl azide did not show any advantage relative to 4-toluenesulfonyl azide (see Sect. 2.6 for methanesulfonyl azide).

(2-78) v

N— Ts

2.198

2.199

No general pattern can be recognized in the reaction of azides with cycloalkenes. Angle strain can greatly enhance the rate of azide addition to cycloalkenes, as shown by work on norbornene and its derivatives (Huisgen et al., 1965), on hexamethylbicyclo[2.2.0]hexa-2,5-diene (Dewar benzene) (Paquette et al., 1972) and related compounds (review: Lwowski, 1984, p. 579ff). Normally, dihydrotriazoles are primary products, followed by a dediazoniation to aziridines. Diazo compounds are formed only in rare cases, e.g., with trifluoromethylated Dewar thiophenes (Kobayashi et al., 1977, 1980). A diazo transfer reaction takes place, however, between diazoalkanes and derivatives of cyclopropene. Thus, in the reaction of dimethyl 3,3-dimethyl-cyclopropene-l,2-dicarboxylate (2.200) with diazomethane, the primary product 2.201, a diaza bicyclo[3.1.0]hexene, isomerizes on irradiation to the diazo compound 2.202 (2-79). Acid catalysis, however, leads to the isomerization of 2.201 to the 1,4-dihydropyridazine 2.203 (Franck-Neumann and Buchecker, 1969). An analogous reaction of

2.7 Diazo Transfer to Alkenes

H3C H3C

73

CH3

CH3

+ H2C=N2 -> H3COOC^

^COOCH3

2.200

2.201

(2-79)

hv

H 3 C X/ CH3

H3Cx/CH3

HsCOOC^ ^C^ ^COOCH3 C C

II

N2

II

CH2

2.202

methyl diazenolate with 3,3-dimethylcyclopropene was found by Aue and Hellwig (1974). Padwa et al. (1983 c) investigated the addition of 2-diazopropane to 1,2-diphenylcyclopropene (2.204). As shown in (2-80) they found that the primary cyclization product l,5-diphenyl-4,4-dimethyl-2,3-diazabicyclo[3.1.0]hex-2-ene (2.205) can undergo a renewed cyclization to form 3,5-diphenyl-6,6-dimethyl-l,2-diazabicyclo[3.1.0]-hex-2-ene (2.206).

(2-80)

2.204

2.205

2.206

The group of Regitz (Regitz, 1975; Heydt and Regitz, 1978; Regitz et al., 1979a; Heydt et al., 1980) investigated the reaction of numerous dimethyl-(cycloprop-l-enyl)phosphonates and (cycloprop-l-enyl)-(diphenyl)phosphine oxides with diazoalkanes in ether at 0°C (2-81). The primary products (2.207) are formed regiospecifically. They isomerize thermally or photochemically in benzene or toluene to the phosphoryldiazo compounds 2.208. Carbonyl-substituted methylene triphenylphosphoranes show similarities to enolates due to their zwitterionic mesomeric structure (2.209). They react with alkyl, aryl, aroyl, and 4-toluenesulfonyl azides. The primary dihydrotriazole is aromatized to the corresponding triazole (2.210)) by loss of triphenylphosphine oxide. Ring opening does not take place, however, with the azides mentioned above. The adiazo-7V-cyanoimine 2.211 is formed with cyanogen azide (R" = CN) (Arnold and Regitz, 1980; Danion et al., 1981; Regitz et al., 1981 b; 2-82).

74

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

(2-81)

R and R' = H, CH3, or C(CH3)3 R" = H, CH3, or PO(C6H5)2 R"' = OCH3 or C6H5 R""and R'"" = H, CH3, C6H5, or PO(OCH3)2

(H5C6)3P^

/Or

or R"—N3

R^J_

L^R' -'H^PO

v^

(2 82)

/-c-c' \ R' R 2.209 R = H, alkyl R' = H, alkyl, aryl, R^zr alkyl, aryl, aroyl, tosyl, CN

'

I for R" = CN R^

2

N/

2.211

a-Diazocarbonyl and a-diazosulfonyl compounds (2.213, X = CO - R and SO2- Ar, respectively) can be obtained (2-83) if the reactive methylene group in the triphenylphosphorane contains a proton as in 2.212. For the formation of adiazocarbonyl compounds 2-azido-3-ethylbenzothiazolium tetrafluoroborate (see Sect. 2.6; 2.144) must be used as diazo transfer reagent (Regitz et al., 1979b). For the synthesis of a-diazosulfonyl compounds, 4-carboxybenzenesulfonyl azide was used (van Leusen et al., 1975; Stackhouse and Westheimer, 1981). a-Diazophosphonium salts (2.215)) can be obtained in good yield from (acylmethyl)(triphenyl)-phosphonium salts (2.214) with 2-azido-3-ethyl-benzothiazolium tetrafluoroborate (Regitz et al., 1981 a). With the acetone-l,3-bis(phosphonium) salt 2.216 it is possible, by this method, to obtain the monodiazo-bis(phosphonium) salt or the bisdiazo-bis(phosphonium) salt, depending on the ratio of the reagents (2-84).

2.8 Diazo Transfer to Alkynes

(H5C6)3P=CH-X

+

75

Y-N3

2.212

"x _ *

(2

"83)

N/°~ 2.213

X = SO2—Ar

or CO—R

C2H5

O II (H5C6)3P—CH2—C —R

+

2.214 |

<-2"5

(2-84)

(H5C6)3PX

,C BF4-

N/ 2 215

-

O II (H5C6)3P-CH2-C-CH2-P(C6H5)3

2 Cf

2.216

2.8 Diazo Transfer to Alkynes The cycloaddition of hydrazoic acid and of organic azides to alkynes to give 1,2,3-triazoles is possible in almost all combinations. Ring opening reactions, in analogy to those of alkenes (see Scheme 2-67), are, in general, possible only with alkynes substituted by amino and alkoxy groups, i. e., with ynamines and ynyl ethers,

76

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

and by using arenesulfonyl azides, methanesulfonyl azide or cyanogen azide. As shown in Schemes (2-85) and (2-86), the primary product is the 1,2,3-triazole with an amino or alkoxy group, respectively, in the 5-position (2.218 and the analog in 2-86). The triazole is in equilibrium with the corresponding diazoalkane 2.219 and 2.220, i.e., with an a-diazoamidine or an a-diazocarbonimidate, respectively (Ynamines: Harmon et al., 1970; Himbert and Regitz, 1972 a, 1973; Arnold and Regitz, 1979; Himbert, 1979; Himbert et al., 1980; Regitz et al., 1981 a; Himbert and Henn, 1981; Himbert and Schwickerath, 1981. Ynyl ethers: Grtinanger et al., 1965; Hermes and Marsh, 1967; Himbert and Regitz, 1972b; Schubert and Regitz, 1982).

(2-85)

2.217

R = H, CH3) COOCH3, COR, alkenyl, etc. R' and R" = CH3, C2H5, C6H5, etc. (R' * R" and R' = R") Ace = SO2Ar, SO2CH3, CN, 3-ethylbenzthiazolium-2-yl Ion, etc.

M

C

8 "N «

M

^

v

N

\* I

/IN2

(2-86)

C

FfO^

N—SO2—R" 2 220

'

R = H, CH3, R = CH R'' = CH3, C6H5, various 4-X-C6H4, mesityl

The equilibrium between the triazole 2.218 and the diazoamidine 2.219 in (2-85) is very strongly influenced by the substituent R in the alkyne and the acceptor part of the azide, as shown for some examples in Table 2-3. The amino group in the 5-position of the triazole 2.218 is necessary for ring opening. For instance, 5-aryland 5-alkyl-l-(4-toluene)sulfonyl-l,2,3-triazoles do not form the corresponding diazoalkane (Harvey, 1966). The amino group of the diazoamidine 2.219 decreases the electrophilicity of the N(/?)-atom in the diazo group, thereby reducing the tendency to recyclize to the triazole. The aryl substituents of the acceptor group Ace decrease the nucleophilicity of the imino group in the sequence given in Table 2-3. As a result, the diazoamidine is the favored equilibrium form in this sequence.

2.8 Diazo Transfer to Alkynes

77

Table 2-3. Triazole ^=^diazoamidine equilibria in additions of azides to ynamines (Scheme 2-85); in CDC13, 40 °C; (Data from Harmon et al., 1970; Himbert and Regitz, 1972 a, 1973). Equilibrium % triazole % diazoamidine 2.218 2.219

R

Ace

CH3

SQAH4-4-N(CH3)2

CH3

S02C6H2-2,4,6-(CH3)3

CH3

S02C6H5

CH3

SO2CH3

CH3

SO^eftH-d

CH3

S02C6H4-N02(2,4or 6)

<5 a )

96 67 62 30

4

33 38 70

<5 a )

>95 a )

a

>95 a )

<5 )

all SO2Ar

H

>95 a )

a

) The authors (Himbert and Regitz, 1972 a, 1973) write 100%/0% in these cases. As the analytical technique (*H NMR) probably did not then allow detection of small percentages, we write > 95%/< 5%.

In the isolation and crystallization of these equilibrium mixtures it is interesting that, with the exception of the last two entries in Table 2-3, the crystallization equilibria are on the side of the triazole. This is also the case for the reaction of arenesulfonyl azides with ethoxyacetylene (Scheme 2-86), although in solution the adiazoimidate 2.220 is strongly favored. If cyanogen azide or 2-azido-3-ethylbenzothiazolium tetrafluoroborate is used as diazo transfer reagent, only the diazoamidines are detected (Regitz et al., 1981 a). This is consistent with the interpretation of the results of Table 2-3. In the context of the rearrangements of triazoles discussed previously, the thermal isomerization (2-87) of alkyl 5-azido-l,2,3-triazole-4-carboxylates (2.221) into 5-diazoalkyl substituted tetrazoles (2.222) and the rearrangement equilibrium (2-88) of COOCH3

N2

COOCHs

N—N

C

//"

f\ C6H5

Y

N

(2-87)

2_222

N—N XN

2.224

(2-88)

78

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

azidotriazoles (2.223) with diazoester substituted tetrazoles (2.224) must be mentioned. Both were discovered by UAbbe's group (UAbbe et al., 1985; UAbbe and Beenaerts, 1989a, 1989b; review: UAbbe, 1990). The reaction of ynamines of type 2.217, in which R is a diphenylphosphinyl group, their sulfur or seleno analog ((C6H5)2P(X), X = O, S, Se), corresponds to that of reaction (2-85). Again, the triazoles are in equilibrium with the diazoamidines (Himbert and Regitz, 1974). A large number of /?-metalyl-ynamines show the same reaction pattern. The metals are trialkylated or triphenylated Si, Ge, and Sn (Himbert et al., 1976). The regioselectivity of addition of arenesulfonyl azides and cyanogen azide to strong donor-substituted alkynes is high, but low with alkyl and aryl azides. These azides of low electrophilicity are not, however, useful for the synthesis of diazo compounds, as the triazole form can be cleaved only in rare cases. Simple alkyl- and arylacetylenes react with azides of all kinds to form triazoles. The regioselectivity of the addition of cyanogen azide to propyne (2-89) is low (Regitz et al., 1981 a). The two isomeric triazoles and diazo-N-cyanoimines are formed in similar proportions. Separation of the isomers was not possible. H

H3C

H

H3C

H3C-C^C-H CH3CN, 45^

—'

"

N3-CN

II

IA (2-89)

H N— CN

H3Cx NC — N

H N2

For acceptor-substituted alkynes, it is possible to use trimethylsilyl azide as transfer reagent (cyanogen azide does not react). The reaction (2-90) is not regiospecific, but the silylated triazoles 2.225 can be hydrolyzed and deprotonated to the anion 2.226. The latter reacts regiospecifically with cyanogen bromide to form the triazole-carbonitrile 2.227, which is in equilibrium with the a-diazo-7V-cyano-imine 2.228 (Regitz et al., 1981 b). Cycloaddition of 1,3-dipolarophiles to alkynes for the synthesis of diazo compounds can also be applied to reaction of diazoalkanes with alkynes (2-91). 2-Diazopropane and 1,2-diarylethynes readily form 3/f-pyrazoles (2.229). These pyrazoles isomerize photochemically to the 4-diazo-2-methyl-3,4-diarylbutenes (2.230), i.e., to a vinyldiazo compound (Pincock et al., 1973; Arnold et al., 1976; Leigh and Arnold, 1979). Some cyclopropene (2.231) is formed in a consecutive dediazoniation, i. e., by cyclization of the carbene formed. The method is not useful for unsymmetrically substituted alkynes because these cycloadditions are not regiospecific. It is, however, applicable to the synthesis of diazoalkenes with alicyclic

2.8 Diazo Transfer to Alkynes R

Ace R—C = C —ACC

N3-Si(CH3)3

V-^/

1. Hydrolysis 2. NaH / THF

Ace \ //O\\

/ N£

N

2.225

2.226

tr R

/ACC

Vc NC-N*

\

-* "-

2.228

R

79

(2-90)

ACC

H NC

2.227

= H or CH3

Ace = COC6H5, COOCH3, PO(C6H5)2,

Ar. \\v

(2-91)

substituents in the /^-position (2.234, 2-92). If diazocyclohexane is to be used, it can be photochemically generated in situ from l,2-diazaspiro[2.5]oct-l-ene (2.232). The spiro-3//-pyrazole 2.233 also isomerizes photochemically (2-92), as shown by Gstach and Kisch (1982). The photochemical isomerization of a 3//-pyrazole into the corresponding vinyldiazoalkane has been studied further by Pincock and Mathur (1982) including the formation of the corresponding cylcopropene (2-93). These authors used an amethyl-/?-phenyldiazoalkane (2.235) for this synthesis. The 3//-pyrazole (2.236) cannot be obtained from 2-diazopropane and 1-phenylpropyne because of the low regiospecificity of the cycloaddition. The authors synthesized 2.235 from the corresponding 4-toluenesulfonylhydrazone with potassium tert-butoxide. In the context of these syntheses of vinyldiazoalkanes, the work of Severin and Pehr (1979) on the formation of 3-diazoprop-l-ene derivatives should be mentioned,

80

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds H3COOC

:N2

COOCH3

H£OOC—C=C—COOCH3

2.232

2.233 (2-92)

hv

H3COOC

COOCH3

\

N2

2.234

(2-93) FT

R = aryl FT = alkyl

although it is not strictly related to this section. Reaction of cyclopentadiene with glyoxal mono(dimethylhydrazone) in the presence of potassium ethoxide yields 5-[(2-dimethylhydrazono)ethylidene]cyclopenta-l,3-diene (2.237). On reaction with hydrazine, the dimethylhydrazino group is replaced by the hydrazino group that is subsequently dehydrogenated to give the 5-(2-diazoethylidene)cyclopenta-l,3-diene 2.238 (2-94). Indene or fluorene can also be used for this synthesis in place of cylcopentadiene. //—& (/ \\ + O=CH—CH=N— N(CH3)2

*•

^\ |

XCH=N-N(CH3)2

>=CH

(2-94)

2.238

2.9 Diazoethene and its Derivatives

81

The diazo transfer from diazoalkanes to alkynes has also been applied to diphenylalkynylphosphine oxides. Low regiospecificity with unsymmetrically substituted alkynes was also observed here (Heydt and Regitz, 1977, 1978).

2.9 Diazoethene and its Derivatives Diazoethene (2.239) is a remarkable molecule because it is highly cumulative and isoelectronic with propadienone (2.240). Unsubstituted diazoethene has not, however, been isolated or experimentally characterized directly, but difluorodiazoethene has (see below).

= C

HgC^C

2.239

2.240

We will discuss theoretical investigations on diazoethene in Section 5.3. Those studies verified the bent structure, as indicated in 2.239 and 2.240. Derivatives of diazoethene have been invoked as highly unstable intermediates in a series of Wittig reactions. Gilbert's group added ketones to dimethyl diazomethylphosphonate (2.241) in the presence of potassium tert-butoxide in THF at - 78 °C. In addition to potassium dimethyl phosphate and molecular nitrogen, dialkylated ethynes (2.246) were isolated. Scheme (2-95) shows the intermediates that are likely for this reaction: C-Alkylation (2.242) is followed by the formation of a 1,2-oxaphosphetane (2.243). Elimination of dimethyl phosphate gives the diazoethene (2.244), from which N2 is eliminated to form the carbene 2.245. The alkyne is formed by the usual 1,2-shift of one of the alkyl groups. The carbene 2.245 can

H3CO

R

P — CH

+

7 C=O

**a II « 2.241

'\

R—C = C —R 2.246

2.245

]

H3COx_

_ |

M3uu g

y

\

(2-95)

82

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

be trapped with protic nucleophiles or with cyclohexene (Gilbert et al., 1979; Gilbert and Weerasooriya, 1980, 1982, and further papers; see Gilbert and Giamalva, 1992, ref. 7). Lahti and Berson (1981) trapped the carbene 2.245 with 3,3-dimethylcyclopropene and isolated the allene 2.246, as well as the corresponding allenes, with 1,3,3-trimethylcyclopropene. These products are expected, if carbene 2.245 is a transient intermediate (2-96).

+ K —- XX

—- '

2.245

/>

(2 96)

-

2.246

Brahms and Dailey (1990) reported the first spectroscopic observation of a substituted diazoethane, i.e., difluorodiazoethene (2.248). These authors irradiated difluoropropadienone (2.247) monochromatically (A = 240 ± 10 nm) in a nitrogen matrix at 11 K (2-97). Difluorodiazoethene reached a photochemical steady state concentration of ca. 2% of that of difluoropropadienone. The diazoethene was detected by IR and verified by the expected spectral shift when working in a 15N2 matrix. \ + ^O

2.247

^

C= F/ \

+C

r

N

°

(2-97)

^N

2.248

Product analyses of thermal reactions, among others also 1,3-cycloadditions, undertaken with a-diazo-a-silylketones (2.249) indicate that diazoethenes are transient intermediates and that these compounds occur in equilibrium (2-98) as /?siloxydiazoalkenes (2.250) (Briickmann and Maas, 1987; Munschauer and Maas, 1991, and references therein).

(2-98) 2.249

2.250

2.10 Synthesis of Alkenediazonium Salts

83

2.10 Synthesis of Alkenediazonium Salts In view of the contrast between the alkanediazonium ions, with their exceedingly weak C — N bond, and the arenediazonium ions, which can be isolated readily as salts, the behavior of alkenediazonium ions is expected to be in an intermediate range of C-N bond stability. It is rather surprising that a systematic search for syntheses of alkenediazonium ions started only in the 1960's. Curtin et al. (1965 a, 1965 b) selected the most obvious approach, namely the nitrosation of alkenylamines (vinylamines). They chose first (1965 a) (2,2-diphenylethenyl)amine (2.251). For reasons that are not clear from their paper, they conducted the diazotization first in refluxing benzene or ether with 2-pentyl nitrite as nitrosating reagent. Under these conditions 1,2-diphenylethyne (2.254) was formed in 50-85% yield. The formation of this product can be interpreted by the hypothesis that 2,2-diphenylethenediazonium ion (2.252) is indeed formed, but that its dediazoniation to the 2,2-diphenylethenyl cation is very fast. This cation rearranges to the 1,2-diphenylethenyl cation 2.253, which forms diphenylethyne (2.254) by deprotonation (2-99). Hanack's group (Alvarez et al., 1993) showed that 7V-silylated imines (2.255) can be nitrosated. The products indicate metastable vinyldiazonium ions and vinyl cations as intermediates.

_

+c5H1l0NO

C— C NH2 2.251

2.252

(2.99)

G—C

2.254

Si(CH3)3

N CH2R 2.255

Attempts to trap the diazonium intermediate 2.252 by addition of nitrosyl chloride to a solution of the amine 2.251 in CH2C12 at -70°C, followed by addition of a methanol solution of the sodium salt of 2-naphthol, gave no azo compound. (It seems to the present author that the reaction conditions for these trapping experiments have not been studied in sufficient detail to be conclusive.) In their second paper, Curtin et al. (1965 b) selected 3-amino-2-phenyl-l/f-inden-l-one (2.256) for

84

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

diazotization. Here, we will not discuss the products isolated (all were N-free) but mention that diazotization with nitrosyl chloride at -10°C in DMSO-THF and other aprotic solvents did not allow trapping of the diazonium ion with 2-naphthol either. More important, the reaction mixture showed the development of an IR absorption at 2090 cm"1, which then disappeared following first-order kinetics. As arenediazonium ions show the NN stretching frequency at 2100-2350 cm"1 and diazoalkanes at 2010-2170 cm"1, the result suggests that the 2090 cm"1 band may be attributed to the alkenediazonium ion 2.257. More recent reviews (Bott, 1973, 1983) show that newer and well defined alkenediazonium salts have NN stretching frequencies in the range 2060-2260 cm"1. It is also possible, however, that the band at 2090 cm"1 is due to the diazoalkane 2.258 formed by addition of chloride ion to C(2) of 2.257 (2-100).

2.256 (2-100)

Newman's group postulated, in a series of papers published between 1951 and 1973 (see Newman and Liang, 1973), the formation of alkenediazonium salts in the alkaline solvolysis of 4- and 5-substituted 3-nitroso-l,3-oxazolidin-2-ones (2.259 in Scheme 2-101). On this basis, Hassner and Reuss later (1974) analyzed a large group of substituted 3-nitroso-l,3-oxazolidinones with respect to products. Their work makes it very clear that these decompositions follow different pathways, depending on the substituents in the 4- and 5-positions and on the reaction conditions. Scheme 2-101 shows that, for 3-nitroso-l,3-oxazolidin-2-ones with an H-atom at C(4) (2.259), an alkenediazonium ion (2.260) is a likely intermediate for the formation of vinyl ethers 2.261 and 2.262, perhaps via the carbocation 2.263. The intermediacy of the carbene 2.264 was indicated by trapping experiments with alkenes, in which alkylidenecyclopropanes 2.265 were detected (Newman and Okoroduru, 1968; Newman and Patrick, 1970; Patrick et al., 1972). Further and important support for the hypothesis of alkenediazonium ions in the decomposition of nitroso oxazolidinones is provided by investigations by Kirmse et al. (1979) with the 15N-labeled nitroso compounds 5,5-dimethyl-3-nitroso-[3-15N]l,3-oxazolidin-2-one (2.259, R' = H; R" = R777 = CH3) and 5,5-pentamethylene-3-nitroso-[3-15N]-l,3-oxazolidin-2-one (2.259, R'= H, R"-R"'= -[CH2]5-). The authors determined the 15N content of products of decompositions conducted in the presence of lithium azide. The results are consistent with TV-coupling of the intermediate with azide ions (for coupling of arenediazonium ions with azide ions see Zollinger, 1994, Sect. 6.4). If a H-atom is also present in position 5 in the nitroso oxazolidinone 2.259 (R"7 = H) dediazoniation gives only disubstituted alkynes (2.266).

2JO Synthesis of Alkenediazonium Salts

85

(2-101)

2.262

2.264

2.265

By intention, we have reviewed that work here only superficially. We agree with the short statement by Stang (1978) that the mechanism of these ring opening reactions is still not completely understood. The work of Newman's and Curtin's groups is, however, worth remembering for its historical significance: One might conclude that alkenediazonium ions have an unexpectedly and surprisingly low stability. This is not generally true, however, because the first alkenediazonium salts were isolated in the mid-1960's, and they had decomposition points above 100 °C. In Sect. 2.1, it was mentioned that a-diazo-/?-carbonyl compounds may be considered to be stabilized by a mesomeric l-diazonio-alkene-2-hydroxide zwitterionic structure, and that a 2-hydroxyalkene-l-diazonium ion may be formed by O-protonation (Scheme 2-3). As shown by Allard et al. (1969) and by Wentrup and Dahn (1970)

86

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

enoldiazonium ions are relatively stable only in superacid media like FSO3H-SbF5-SO2 and HF-SbF5-SO2 at temperatures below -60°C. Stability is expected, however, to be better in /?-diazo-a,)>-dicarbonyl compounds due to more extended resonance. This is indeed the case, as shown by Bott (1964, 1966), if hydrogen chloride, antimony pentachloride, and various diazodicarbonyl compounds are dissolved in CH2C12 (2-102). N2 II ^'^'•^

^C^ II °

/fi

+ HCI + SbCU

*» (2-102)

SbCI6~

2.267

Crystalline salts of diazonium hexachloroantimonate 2.267 can be isolated. The O--H — O bond obviously increases the stability. Chlorides are not stable, presumably because HCI is evolved, whereas the vapor pressure of SbCl5 is low. In addition to protonation, the six-membered ring can also be formed with Lewis acids, for example in the case of diazomalonic ester (2.268) by two equivalents of SbCl5. One antimony tetrachloride cation acts as a Lewis acid and the second as counter ion (SbClg"). Analogous salts are formed with boron trifluoride (2.269). The alkenediazonium salts (2.271) obtained by Regitz and Schwall (1969) from imines of 2-diazoindane-l,3-dione (2.270) are remarkable because protonation takes place with mineral acid in aqueous ethanol and because these alkenediazonium salts should be regarded in the context of the failure of Curtin's group (1965 b) to obtain an alkenediazonium salt by diazotization of 3-amino-2-phenyl-l//-inden-l-one CI4

SbCI6-

N2+-C

§F2 BF4

W N2+

2 268

= CH3, C6H5 = C6H5, C6H5

2269

2.10 Synthesis of Alkenediazonium Salts

87

(2.256). The imines of 2-diazoindane-l,3-diones have carbonyl-like functions in both neighboring positions to the diazo group and an imino N-atom, which is, of course, much more basic than a carbonyl O-atom (2-103).

+ H+

ii

i

\

i

i

\

M

+

(2-103)

X = H, 4-NO2, 4-CI, 4-I, 4-CH3, 4-OCH3 2.270

2.271

Another stable salt is the protonated product 2.273 of phenyl(pyridin-4-yl)diazomethane (2.272), which was discovered by Reimlinger (1963, 1964). The relatively low NN stretching frequency (2060 cm"1) indicates, however, that this compound may not be classified as an alkenediazonium ion, but rather as a diazoalkane, protonated at a relatively remote heterocyclic N-atom (2-104).

(2-104)

cci3—co22.273

If a reagent with an electrophilic C-atom is added instead of a proton to a a-diazo-/?-carbonyl compound a much more favorable equilibrium is obtained. Bott (1964, 1966) added the Meerwein reagent triethyloxonium hexachloroantimonate to ethyl diazoacetate (2.274) and to (4-nitrophenyl)-diazoacetic-acid piperide (2.276) and obtained the isolable alkenediazonium salts 2.275 and 2.277 (2-105 and 2-106).

sbc,6 +0Et336^ o* 2.274

Eto

x

EtO

^_^

/H

Eto ^

^

N2

; ,

N^ EtO

2.275

^

SbCI6~

(2-105)

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

+ OEt3SbCI6 ^ -OEt 2

(2-106)

SbCI6~

2.277

In 1971, Bott showed for one case that alkenediazonium salts can be obtained by nitrosation, not of aminoalkenes, but from their isocyanate derivatives (2.278) with nitrosyl hexachloroantimonate under aprotic conditions (CH2C12). By this method, 2,2-dichloroethenediazonium hexachloroantimonate (2.279) was synthesized in 40% yield (2-107). It may be mentioned that this nitrosation cannot be used for aromatic isocyanates: nitrosyl cations attack phenyl isocyanate by nitrosation of the aromatic ring, as shown by Olah et al. (1966).

cr

C=C/

2.278

P

H

>

cr

/C =

C

v

SbCI

H

6~

+ C

°2

(2-107)

2.279

Curtin et al. (1965 a) investigated the nitrosation of 9-(aminomethylidene)fluorene without being able to find convincing evidence for an alkenediazonium ion as metastable intermediate. 9-(Diazoniomethylidene)fluorene (2.281) was obtained, however, by Bott (1970, 1975) from two sources, namely the corresponding 4-toluenesulfonylazoalkene (2.280, an "azofulvene"), by addition of SbCl5 and HCI, and from fluorene-9-carbaldehyde 4-toluenesulfonylhydrazone (2.282) with SbCl5 (2-108). In the second synthesis Bott assumes that antimony pentachloride is an oxidizing agent besides its Lewis acid function. A similar synthetic method was used by Bott (1975) for preparing 2-chloro-3methylbut-1-ene-diazonium tetrachloro-(4-toluenesulfinato)stannate (2.184) from 2,2-dichloro-3-methylbutyraldehyde-4-toluenesulfonylhydrazone (2.283) in dichloromethane using stannic chloride as reagent (2-109). Whereas HCI was added in the reactions with SbCl5, this is apparently not the case for the reaction with stannic chloride. Bott did not investigate or explain this difference, nor did he determine the configuration at the C = C double bond.

2.10 Synthesis of Alkenediazonium Salts

89

[Ts-2SbCI5]"

(2-108)

2.281

2.282

X N—NH—Ts (CH3)3C—CCI2—CHX + SnCI4

2.283 -HCI

(2-109)

/H N2+

Cl

2.284

Seven alkenediazonium hexachloroantimonates and three alkenediazonium tetrachloro(4-toluene-sulfinato)stannates were synthesized by Bott (1975). All except the 2-chlorobut-l-enediazonium hexachloroantimonate can be isolated, and all decompose in the solid state, depending on substituents, in the range 50-132°C. It seems that the stability, as reflected in the decomposition temperature, is related to the stability of the vinyl cations formed. A systematic investigation of these problems, which could define the potential of alkenediazonium ions for synthetic applications, would be desirable. At present, there are very few reactions known of alkenediazonium ions that have such a potential (see Sect. 9.5). Lorenz and Maas (1987) found a novel route to alkenediazonium salts in the O~ acylation of a-diazo ketones with benzoyltriflate or diphenylacetyl triflate, i. e., with carboxylates with a very weak base, in dichloromethane at — 70 °C (see Scheme 9-50). They are not stable at higher temperature, but form 1,3-dioxolium salts (see Sect. 9.5).

90

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

Theoretical papers on alkenediazonium ions will be discussed in the context of the structure of diazonium ions in Section 5.3. Alkenediazonium salts are of potential interest for azo imaging systems, because diazonium ions of type 2.285 were calculated by the Pariser-Parr-Pople (PPP) approximation to have absorption maxima in the visible part of the electronic spectrum (n = 1:452 nm; n = 2:534 nm, Walkow et al., 1980). As such diazonium salts are, however, thermally very unstable, they cannot be used for such purposes. Nevertheless, Walkow et al. found that benzenediazonium ions with an ethenyl group in the 4-position (2.268) show a similar bathochromic shift. Synthesis (2-110) of compounds with an a-cyanostilbene-4-diazonium structure (2.287, n = 1) and the vinylogous butadiene compound 2.287 (n = 2) is straightforward (Walkow et al., 1980; Walkow and Epperlein, 1984). Their use in a multicolored azo imaging system has been described by Marx (1990) and reviewed by Zollinger (1991, Sect. 14.4).

2.285

n = 1 or 2

2.286

n = 1 or 2

(H3C)2I

(H3C)2N^

?—(CH*

(2-110)

(H3C)2N-/

^ 2.287

n = 1 or 2

2.11 Synthesis of Compounds with a Csp-attached Diazonio Group

91

2.11 Synthesis of Compounds with a Csp-attached Diazonio Group As mentioned in the preceding section, alkenediazonium salts are thermally fairly stable. One might conclude therefore that alkynediazonium salts might also be stable. Tedder and Robson (1963 a, 1963 b) described a synthesis of hex-1-ynediazonium nitrate, starting with the nitrosation of dihex-1-ynyl mercury with nitrosyl chloride and followed by diazotization with nitric oxide, i. e., a modification of Tedder's so-called direct introduction of the diazonio group (see Zollinger, 1994, Sect. 2.6). The authors claimed to have detected the diazonium salt by its capability to form an azo compound with 2-naphthol. Robson et al. (1963) also published a communication in which they described the diazo transfer from 4-toluenesulfonyl azide to (hex-l-ynyl)lithium. These two methods, however, could not be reproduced by Helwig and Hanack (1985). The classical synthesis of diazonium salts is not applicable to alkynediazonium salts, because primary ynamines are inaccessible. They are prototropic isomers of the much more stable nitriles. Helwig and Hanack (1985) were, however, successful with a synthetic method that was useful for the formation of alkenediazonium salts, namely the elimination of hydrogen halide from 1-halogenoalkanal (4-toluene)sulfonylhydrazones and dissociation of the product, the alkene(4-toluene)sulfonyldiazenes, into alkenediazonium salts with the help of Lewis acids (see Sect. 2.10, Scheme 2-109). By analogy, 1,2-dihalogenoalkanal (4-toluene)sulfonylhydrazones should form alkynediazonium salts. This pathway was indeed successful (2-111). C6H5—CH—C = N—NH— Ts

Br

Cl 2.288

N(C2H5)3

- HN(C2H5)3Br

= C — N=N—Ts SbCI6~

/=\ H

N2+ SbCI5Ts~

I * C6H5—C=C —N=N 2.291

SbCI5Ts~

(2-111)

92

2 Methods for the Preparation of Alkane, Alkene, and Alky ne Diazo Compounds

Starting with 2-bromo-l-chloro-2-phenylacetaldehyde (4-toluene)sulfonylhydrazone (2.288) (l-chloro-2-phenylethenyl)(4-toluenesulfonyl)diazene (2.289) was obtained with triethylamine in ether. A solution of the diazene in methylene chloride becomes greenish after addition of antimony pentachloride at — 30 °C. Above -20°C N2 is evolved. At -70°C, however, a red solution is formed. The latter develops N2 even at — 60 °C. The red solution corresponds to the l-chloro-2-phenylethenediazonium ion 2.290 (2-111). The structure of 2-phenylethynediazonium ion (2.291) can be attributed to the compound in the greenish solution on the basis of the IR spectrum (C = C at 2150 and 2255 cm-1, -N==N at 2295 cm-1) and of the following reactions with nucleophiles. The dominant property of the alkynediazonium ion 2.291 is the addition of nucleophiles to the triple bond. Addition of water or methanol to the CH2Cl2-SbCl5 solution leads to alkenediazonium ions 2.292 with OH, CH3O or Cl in the 2-position (2-112). The C — N bond in the alkynediazonium is more stable than the corresponding C — N bond of the alkenediazonium ion. With water, the final product of addition, dediazoniation of the alkenediazonium ion, and addition of HC1 is 2-chloro-l-phenylethanone (2.294). Without HC1, 2-hydroxy-l-phenylethanone (2.293) is formed (2-113). C6H5— C=C — N2+ SbCI5Ts- — ^-*-

C=C X/

(2-112) \2+

SbCI5Ts-

2.292 X = OH, OCH3, or Cl

O

C6H5-C-CH2OH 2.293 C6H5-C=C-N2+

H0O

—^

C6H5-C-CH2-N2+

-N

—

(2-113)

O C6H5— C— CH2CI 2.294

The higher stability of the alkynediazonium ion towards dediazoniation, relative to that of the alkenediazonium ion, is consistent with structure calculations obtained by Glaser (1987, 1989; see Sect. 5.3). It is unlikely, therfore, that alkyne cations can be obtained by dediazoniation of alkynediazonium ions. An alkynyl cation was formed, however, by spontaneous nuclear decay in l,4-bis(tritioethynyl)benzene, as found by Angelini et al. (1988). Another system that contains a Csp-attached diazonium function is the cyclopropeniumdiazonium salt 2.295. 2,3-Bis(dialkylamino)cyclopropeniumdiazonium salts (2.296) were synthesized successfully by Weiss et al. (1985) by four different routes (Scheme 2-114).

2.11 Synthesis of Compounds with a Csp-attached Diazonio Group

93

I2+ 2X~

2.295

2.296

R

2.300

— CHg,

/- CgHy

X' = BF4- SbCI6~

2.299

All these routes start from cyclopropenium salts, which can be obtained from the same type of starting material, namely l,2-bis(dialkylamino)-3-chlorocyclopropenium salts. Route A involves the classical diazotization of l,2-bis(diisopropylamino)-3-aminocyclopropenium tetrafluoroborate (2.297, R = 2-C3H7, X~ = BF^r), but with removal of water generated in the diazotization (addition of two equivalents of trimethylchlorosilane and use of nitrosyl hexachloroantimonate as nitrosating reagent in dry dichloromethane). Route B represents a novel method, namely a detert-butylating diazotization of l-(te^butylamino)-2,3-bis(dimethylamino)-cyclopropenium tetrafluoroborate (2.298, R = CH3, X~ = BF4- or SbCl6~) under the same conditions as route A. For routes C and D, l-hydrazino-2,3-bis(diisopropylamino)cyclopropenium tetrafluoroborate (2.299, R = 2-C3H7) and the corresponding dication 2.300, dehydrogenated in dry dichloromethane with SOC12 or Id, are used. Method D gave better results than C: Yields with methods, A, B and D were around 90%, with C 69-90%. The IR spectra of all diazonium salts 2.296 exhibit an intensive absorption for the diazonio group between 2130 and 2155 cm"1. Reactions with most nucleophiles result in either no reaction or total destruction, leading to dark oils or tars, besides loss of N2. The diazonium salts react smoothly, however, with water to give 2-(dialkylcarbamoyl)-2-(dialkylamino)ethenediazonium salts 2.301 (2-115). Thermolysis of the solid hexachloroantimonate salt at 130 °C resulted in the l,2-bis(dialkylamino)-3-chloro-cyclopropenium antimonate 2.302 (25%), i.e., in a Balz-Schiemann chloro-de-diazoniation, in addition to unidentified products.

94

2 Methods for the Preparation of Alkane, Alkene, and Alkyne Diazo Compounds

-N 2

O 2.301

SbCle-

CH2c,2

^

^

„,

(2-115)

2SKV

2.296

Addition of a 3-4 M excess of HBF4 to a suspension of these cyclopropenium-1-diazonium salts converted them in near quantitative yield to bright yellow salts, which analyzed correctly for the addition of HBF4. Normal BF^~ and SbClg" vibrational modes in the IR spectra indicate a protonation of this small dication — a rather surprising result. The protonation site is open, however, for discussion. Topological analyses of the electron density functions of the cyclopropeniumdiazonium dication and its 2,3-diamino derivative have been published by Glaser (1990). We will discuss them in Section 5.3.

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

3.1 Addition Products of Dinitrogen to Nonmetallic Inorganic Species As there is a fairly large number of inorganic compounds that contain a primary amino group, it is of interest to briefly review how they react under the nitrosation conditions that are usually employed in the preparation of organic diazo and diazonium compounds. Good examples to start with are ammonia, the simplest amine, and its hydroxy derivative, hydroxylamine. Both react readily with nitrous acid in acidic aqueous solution, as shown in Schemes (3-1) and (3-2): ammonia yields molecular nitrogen. This method was used as a preparative process for N2 decades before fractionation of air became commercially available. The product of the corresponding reaction of hydroxylamine is dinitrogen oxide (originally called nitrous oxide). NH3 + HNO2 HO—NH2 + HNO2

>-

N2 + 2 H2O

(3-1)

>• O=N—N + 2 H2O

(3-2)

Surprisingly, the mechanisms of these two reactions were not investigated until quite recently. Olah et al. (1985 a) obtained 14N15N when they treated 14NH3 with 15 NO + BEj~, which is consistent with a diazotization mechanism (3-3)-(3-5) analogous to that of a primary aliphatic amine involving protonated dinitrogen (H — N = N) as intermediate, i. e., the parent ion of the whole class, of inorganic and organic diazonium ions. According to IUPAC nomenclature, N2H + is called the diazynium ion (Chatt, 1982). Attempts by Olah et al. to protonate N2 in HF-SbF5, one of the strongest superacids, have not been successful. This result is hardly surprising if the mechanism of addition of N2 to a phenyl cation is considered: Zollinger (1987, 1990) has demonstrated that the electrophile must provide an empty o orbital and rc-back donation. Nevertheless, N2D+ has been observed in a mass spectrometer by Shannon and Harrison (1965) in mixtures of N2 and tetradeuteromethane. Under such conditions it is likely that N2D+ is formed in reactions shown by (3-6) and (3-7). A kinetic investigation of the nitrosation of ammonia in aqueous acid solution in the range 0.5 — 0.20 M for hydrogen-ion concentration [H + ] was conducted by Bryant and Williams (1988). In contrast to earlier and less reliable kinetic work, they found a first-order dependence on [NH/] and on [HNO2], and a zero-order dependence on Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

96

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand (3-3) H—N^N + H2O

(3-4) (3-5) (3-6)*) (3-7)*)

acid. The reaction is strongly catalyzed by both bromide and thiocyanate ion. The kinetics are, therefore, consistent with a mechanism in which BrNO or ONSCN reacts with the free base NH3 in the rate-limiting step. The N-nitrosoammonium ion formed rapidly decomposes to give, ultimately, N2. This mechanism is completely analogous to the diazotization of aromatic amines (see Zollinger, 1994, Sects. 3.2-3.4) and, with respect to the rate-determining part, to the formation of N-nitrosodialkylamines (Sect. 4.1 of this book). Lines have been found in spectra of interstellar space that Turner (1974) and Green et al. (1974) interpreted as being due to the diazynium ion. Protonation of dinitrogen has been investigated by theoretical chemists for twenty years (Hillier and Kendrick, 1975; Chadha and Ray, 1982; Del Bene et al, 1982; Botschwina, 1984; DeFrees and McLean, 1985; Kraemer et al., 1986; Glaser et al., 1993 a). Although all these investigations came to the conclusion that the three atoms in HN/ are in a linear arrangement and that a bridged structure [^]+ is energetically less favorable, we will concentrate the discussion on the second paper of Glaser's group (1993 a). They determined optimized structures for the linear and the bridged arrangements at RHF, MP2, and CISD (full) levels, including vibrational zero-point energy corrections (6-31G* and 6-311G (df, p) basis sets). The best estimate for the proton affinity is 486 kJ mol"1; the dissociation of HN^ into the H atom and the N2+ radical cation is endothermic by 635 kJ mol"1. The bond lengths are 102.7 pm (HN) and 108.4 pm (NN) on the CISD (full)/6-311G (df, p) level**. The bridged structure does not represent a minimum on the potential energy surface. It is, therefore, a transition state between H — N(a) = N(/?) and N(a) = N(/J) — H. The rearrangement has a calculated activation energy of 220 k J mol ~l. It is remarkable, however, that the more stable form of protonated diphosphorus (HP/) is the bridged structure. The proton affinity of P2 is, as expected, higher (674 kJ mol"1). We will discuss phosphorus analogs of organic diazonium ions in Section 5.3. In contrast to ammonia, the reaction of hydroxylamine reflects the nitrosation of organic amines with an electron withdrawing substituent at the C(a)-atom, e.g., aminoacetate (1.1): the hydroxy group acidifies the NH part on the one hand, and, on the other, it will readily lose the proton after the strongly acidifying diazonio group has * Schemes 3-6 and 3-7 are given as published by Shannon and Harrison (1965). ** For comparison the NN distance in N2 was calculated on that level to be 109.0 pm (experimentally 109.76 pm, Davis and Ibers, 1970).

3.1 Addition Products of Dinitrogen to Nonmetallic Inorganic Species

97

been formed (see Zollinger, 1994, Sect. 7.3): the reaction product, dinitrogen oxide (3.1), is isoelectronic with diazomethane (3.2). H

O=N=N H

3.1

\ C=N=N

:C=N=N

3.2

3.3

Diazomethylene (3.3) and diazomethane are structurally similar, but not isoelectronic. In 1960, Robinson and McCarty tentatively assigned a band at 424 nm to diazomethylene in the photodecomposition of diazomethane (in solid krypton, 4.2 K). At the same time, Milligan and Jacox (1960) independently prepared diazomethylene by the photolysis (210-280 nm) of matrix-isolated cyanogen azide. It is likely that diazomethylene is formed by homolytic dissociation of cyanogen azide into an azide and a cyanide radical, recombination to the isocyanogen azide, formation of atomic carbon and dinitrogen, and attack of the C-atom on N2 (3-8)-(3-10). The last step of this mechanism is supported by the trapping of the C-atoms in a pure N2 matrix (Weltner and McLeod, 1964; DeKock and Weltner, 1971). (3-8) (3-9)

(3-10)

Diazomethylene is interesting, as its structure is a combination of those of diazomethane and methylene (: CH2), the latter being the product of dediazoniation of diazomethane. Its chemical reactivity has not been investigated systematically, although its IR spectrum is well known (see summary of Jacox, 1984, p. 966). The UV emission spectra obtained by exciting matrix-isolated diazomethylene with dye lasers in argon at 10 K have been investigated by Wilkerson and Guillory (1977)*. The close relationship between diazomethane, hydrazoic acid, and dinitrogen oxide is evident on the basis of energies (kJ mol"1) of their highest occupied molecular orbitals (HOMO) and lowest unoccupied orbitals (LUMO) (Houk et al., 1973a; Houk and Yamaguchi, 1984), as well as of their dipole moments (DP, in D):

N2 = CH2 LUMO

+12.7

HOMO -63.5

DP

1.5

N2 = NH

N2 = O

+0.7

-0.7

-75.5

-85.4

0.85

0.17

* The methylidyne radical (CH") was detected by Becker et al. (1984) during the photolysis of diazomethane in the presence of H- and O-atoms.

98

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

The decrease in the dipole moments in that series indicates an increasing charge cancelation in the resonance hybrid N = N = X<-»N = N-X (see also Sect. 5.2). The replacement of X = C by the more electronegative heteroatomic groups NH and O reduces the intra-orbital repulsion and, thereby, the orbital energies. That diazomethane, however, cannot be obtained by straigtforward nitrosation of methylamine is due to the higher stability of the C — H bond compared with that of the C -N(a) bond in the methanediazonium ion, as already discussed in Sections 2.1 and 2.2. There are additional correlations between the kinetics of hydroxylamine nitrosation and the kinetics of aniline diazotization, as shown by Hughes and Stedman (1963) and by Hughes et al. (1968). At low acidities of aqueous perchloric acid, dinitrogen trioxide reacts with free hydroxylamine, corresponding to region A in Ridd's mechanistic evaluation (1965) of the diazotization of aniline (see Zollinger, 1994, Fig. 3-1, p. 46). At higher acidities, the nitrosyl cation reacts with both free hydroxylamine and the 7Vprotonated form (3.4). The overall reaction rate is too high to involve the O-protonated hydroxylamine (3.5), which is present only in extremely low concentration in the acidic media applied by Hughes and Stedman (aqueous HC1O4). The equilibrium between the two protonated isomers of hydroxylamine (Scheme 3-11) is strongly in favor of the 7V-protonated form 3.4. Therefore, Hughes and Stedman suggested that the nitrosating species replaces a proton of the hydroxylammonium ion 3.4. HO—NH2

+ H+

"*XN.

a(0

> H

\r\

KIII

w

i^r"i3

3 4

-

(3-H) \

+

O

NH

'

H^ 3.5

In analogy to Ridd's work with aromatic amines, it is possible that the O-atom of the hydroxylammonium ion 3.4 provides electrons for the formation of a chargetransfer complex 3.6 with the NO+ ion (3-12). For obvious reasons, the NH^" group of complex 3.6 is much more acidic than the NH3+ group in uncomplexed hydroxylammonium ion 3.4: pKa(3A)>pKz(3.6)- As suggested by Zollinger (1988), complex 3.6 will, therefore, lose a proton of the NH3+ group relatively easily. The NO+ group of the complex 3.7 can subsequently be rearranged to the hydroxy-nitrosoammonium ion 3.8, which, in turn, will lose another proton, leading to 7V-nitrosohydroxylamine 3.9 (3-12). O-deprotonation of 3.8 is, of course, also possible. This process is more dominant than 7V-deprotonation to 3.9. It can be omitted, however, in this context, since Odeprotonation is a side-equilibrium that does not lead to the reaction product N2O. 7V-Nitrosohydroxylamine (3.9) gives dinitrogen oxide in the usual way (3-13) via the hydroxydiazonium ion. At a very early time, this mechanism was investigated using 15 N-labeled nitrous acid and O-alkylated hydroxylamines (Leffler and Bottner-By, 1951).

3.1 Addition Products of Dinitrogen to Nonmetallic Inorganic Species N0+

1 HO—NH3

99

N0+ -H+

<

»

I HO—NH2

+

+H

3.6

3.7

(3-12)

HO—NH

<

3.9

NO I HO—NH —*—**

.

.

HO—NH2 3.8

HO—N=N

>* O— N=N

(3-13)

Nitrosation products of inorganic amines in aqueous systems were investigated by Fitzpatrick et al. (1984) and summarized by Williams (1988, p. 104ff). The availability of superacid systems made it possible to study some further inorganic diazonium ions. Fluorodiazonium hexafluoroarsenate (F — N = N AsF^f; a white solid) was first prepared by Moy and Young (1965) by fluoride ion abstraction from (Z)-difluorodiazene by AsF5 at low temperature (3-14) (see also Bormann and Glemser, 1966; Pankratov and Savenkova, 1968). Christe et al. (1991) prepared the corresponding hexafluoroantimonate salt FN2+ SbFg". F—N=N AsF6-

(3-14)

The fluorodiazonium ion is interesting, because ab initio calculations of Pulay et al. (1975), Peters (1987) and Yakobson et al. (1988) indicated the presence of a surprisingly short N —F bond (123-128 pm). These results were confirmed by investigations of Glaser and Choy (1991) at more sophisticated levels (RHF/6-31G* and MP2 (full)/6-31G). In a crystal structure determination of FN2+AsF6~, Christe et al. (1991) found that FN/ is linear, as expected, but that only the sum of the NF and NN bond lengths could be determined. The partitioning of this sum was achieved by local-density functional calculations, providing both the geometry and the vibrational frequencies. Values of 122 pm and 110 pm were found for the NF and NN bond lengths, respectively. This is the shortest NF bond known so far, while the NN bond length is comparable with that of N2 (109.8 pm), and with that of other diazonium ions (see Zollinger, 1994, Table 4-1, p. 67).

100

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

Christe et al. (1991) also showed that fluorodiazonium hexafluoroarsenate is an extremely good fluorinating agent. For example, it reacts with xenon forming a xenonfluoronium salt (3-15). It is not, however, an efficient fluorination agent for aromatic compounds (Olah et al., 1985b). FN2+ AsF6- + Xe

*

>

XeF+ AsFef

+ N2

(3-15)

Schmidt (1966) described the preparation and IR spectra of the hydrohexachloroantimonates of methyl azide and hydrazoic acid, and viewed them as aminodiazonium salts. A more detailed study of the protonation of methyl and ethyl azides, as well as of hydrazoic acid, under superacidic conditions was carried out by Olah's group (Mertens et al., 1983). Protonation with FSO3H-SbF5, HF-SbF5, or HF-BF3 resulted in the formation of stable aminodiazonium ions, as shown by *H, 13C, and 15 N NMR. More recently, Olah and Ernst (1989) found that aminodiazonium ions are also formed if trimethylsilyl azide is dissolved in trifluoromethanesulfonic acid (triflic acid). The aminodiazonium triflate (H2NN^OSO2CF3~) acts, by dediazoniation, as a synthon for "NH^", which is a strong electrophile: in the presence of benzene or substituted benzenes, the corresponding aromatic amines are formed in high yields (in most cases 93-96% based on the azide used). Glaser and Choy (1991) investigated the aminodiazonium ion theoretically at the RHF/6-31G* and the MP2(full)/6-31G* levels. As for other ions of type X — N^ (X = H, HO, and F), they found that linear arrangements of the three central atoms (not the H atom in OH and NH2 groups) represent energy minima in contrast to bridged structures. Cyanodiazonium tetrafluoroborate (NC-N/BF<j~) was generated by Olah et al. (1985 b) by nitrosation of cyanamide with NO + BF^r in dichloromethane, in acetonitrile, or in thionyl chloride. The cyanodiazonium ion readily decomposes, undergoing rapid dediazoniation. Following an analogous procedure, nitrodiazonium ion can be formed from nitroamide. For the methoxydiazonium ion (H3CO-N^), Olah et al. (1986) methylated dinitrogen oxide at the O-atom with methyl fluoride and SbF5 in SO2F2, or with CH3O + -SOClF-SbF6- in SO2C1F at -80°C. The methoxydiazonium hexafluoroantimonate precipitates and can be dissolved in methyl fluoride. Attempts to prepare the hydroxydiazonium ion (HO — Ns N) by protonation of dinitrogen oxide in the strongest superacids known, such as SbF5 - HF (1:1) and SbF5-FSO3H (4:1) in SO2C1F, provided no direct evidence for the hydroxydiazonium ion. On the basis of the concept of isoelectronic structures, which we applied above for the comparison of dinitrogen oxide and diazomethane, the hydroxydiazonium ion should be compared with the isoelectronic methanediazonium ion, which had been observed applying several techniques (see Sect. 5.1). The lower stability of the hydroxydiazonium ion is understandable, however, because the O — H bond is weaker than a C — H bond in the methanediazonium ion. The hydroxydiazonium ion was also considered in the theoretical evaluation of compounds X — N^ by Glaser and Choy (1991) mentioned above.

3.2 Diazo Derivatives of Polyhedral Boron Hydrides

101

Inorganic diazonium salts have been reviewed by Laali and Olah (1985). Diazosilane (SiH2N2) is an inorganic analog of diazomethane. It has not yet been observed or isolated, but its structure and stability were calculated by Thomson and Glidewell (1983) using MO methods. They are discussed in the section on isomers of diazomethane (Sect. 5.4).

3.2 Diazo Derivatives of Polyhedral Boron Hydrides All inorganic diazonium ions (X-N 2 + ) discussed in Section 3.1 are characterized structurally, first, by a small group X consisting of one to five atoms, and, second, by little or no stabilization of the X —N(a) bond. These inorganic diazonium ions are, therefore, comparable to simple aliphatic diazonium ions, e.g., H3C —N/. There are, however, also a few inorganic diazo compounds in which X has 18 or more atoms and, in addition, the members of this group have a stability and reactivity comparable to those of aromatic diazo compounds. These are the mono- and bis(diazo)boranes, which were discovered by the group of Muetterties in their work on cluster-type boron hydrides (Knoth et al., 1964). Before discussing these diazo compounds, we will briefly review the chemistry of cluster compounds of boron hydrides. It is a field of inorganic chemistry that showed a tremendous increase in the number of substances known during the past three decades (see the books of Muetterties, 1975, and Housecroft, 1990). A characteristic of these substances is that their structures are polyhedra, called deltahedra, because they are made up of triangular faces. They are stable and well characterized by X-ray investigations and by HB NMR spectroscopy *, but they cannot be adequately rationalized in terms of two-center electron pair bonds. In many clusters, each atom appears to be bound to several other atoms. Boron hydrides (boranes) and carboranes (i.e., boranes in which one or more formal BH~ groups are replaced by CH groups) contain too few electrons to allow two-center bonds. There are various solutions for the valence problems posed by boranes and carboranes, first of all the postulate of three-center electron pair bonds. Such bonds are not simply a formalism, but they can be integrated into MO treatments that, when applied to questions of structure and stability, lead to results that fit experimental data. It is remarkable that this postulate was applied to investigations on boranes at an early

* The term 'cluster' should not, however, give the impression of a disordered structure. It was used first by Cotton (1966) for compounds that contain a group of two or more metal atoms in entities with direct and substantial metal-metal bonding. Later, the term was extended to other compounds with such bonds between main group elements. For an introduction to cluster chemistry in general, see the monograph of Mingos and Wales (1990).

102

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

date*, as can be seen in Lipscomb's classical monograph (1963), and later in books and reviews by Wade's group (Wade, 1971, 1976; Coates et al., 1967). Wade also wrote a short review on cluster shapes for nonspecialists (1975). Modern textbooks of advanced inorganic chemistry also contain this subject (e.g., Cotton and Wilkinson, 1988, p. 179; Shriver et al., 1990, p. 627). Boranes and carboranes have structures in which their skeletal B- or C-atoms form triangular-faced polyhedra. There are basically three structural types, namely the closo- (an euphonious modification of the Greek clovo = cage, i. e., a complete or 'closed' polyhedron), the nido (from Latin 'nest-like') and the arachno- (from Greek 'cob-web') structure**. Each of these three types is adopted by cluster compounds of specific atomic ratios. c/oso-Structures occur in borane dianions RnH%~, in carborane anions (CB^.iH^)", and carboranes (C2BAZ_2H,Z). Each skeletal atom has a single H-atom terminally attached by a bond directed outwards, away from the polyhedron center (see the example of B10H?0~ in Fig. 3-1 below). m'rfo-Structures are adopted by boranes B^H^+4 and their related carboranes CEn_iHn+3, ^2^n-2^n+2 etc., and tfrac/mo-structures by boranes B^H^+6 and related carboranes CB n _!H w+ 5, C 2 B A j_ 2 H w+4 etc. In other words, carboranes have the general formula [(CH)a(EH)bHc]x~, where the sum (a + c + x) is equal to 2 for a closostructure, 4 for a mdo-structure, and 6 for an #rac/mo-structure. Wade (1976) derived a set of guidelines, the so called 'Wade's rules', for relating the structures of boranes to their composition. They are based on the results of MO calculations and pertain to boranes of the type B W H^~, where m > n and x > 0. For m = n, Wade's rules predict that the c/oso-structure is preferred. Analogous rules apply to the nido- and arachno-types. We will not discuss these two types, because only c/oso-structures have been found for diazoboranes. In addition to Stock's experimental work, as well as Lipscomb's and Longuet-Higgins theoretical investigations, and pioneering X-ray structure studies by Lipscomb and others (mentioned, in part, above; see also Lipscomb's book, 1963), nB NMR spectroscopy was very helpful for structural elucidations. With the advent of twodimensional correlation spectroscopy techniques (2D-COSY) (see Ernst et al., 1987; Ernst 1992), uncertainties in assignment of peaks have been considerably reduced, as shown by the work of Wade (1991) on derivatives of 1,2-carboranes (C2B10H12) and others (see review of Beaudet, 1988). Structural and electronic aspects of boranes and carboranes have been summarized by various authors in the book edited by Olah et al. (1991).

* It is said that three-center electron pair bonds were postulated first by Longuet-Higgins in a seminar he gave as an undergraduate student at Oxford (Longuet-Higgins, 1949, see also his review published in 1957). He had also predicted the existence of the icosahedral B12Hi2~ ion by an LCAO-MO approach before it was synthesized (Longuet-Higgins and Roberts, 1955). Hydrides of boron had been known since the turn of the century, but prior to the investigations of Stock in the 1920's and 1930's, all of the proposed structures were incorrect. ** In c/oso-structures, there is a B- or C-atom at each vertex of the deltahedron; nido- and arachno-structures are formally derived from c/oso-deltahedra with one and two missing vertices, respectively.

3.2 Diazo Derivatives of Polyhedral Boron Hydrides

103

The c/050-borane dianions (B^H^") are particularly interesting for the content of this book because of the type of reactivity by which they are characterized, described by Muetterties and Knoth (1968). All closo-ions are comparable to aromatic hydrocarbons in that the delocalized bonding MO's are completely filled, and the LUMO's lie considerably higher in energy. Therefore, electrophilic substitution reactions are possible for these compounds. The ions B10Hi0~ [decahydro-decaborate (2 — ), Fig. 3-1] and B12H?2~ are hydrolytically stable and have been the most thoroughly studied. Many electrophilic substitutions have been studied (summary, see Housecroft, 1990, Scheme 7.3.1, p. 145). Halogenation of B10H?0~ and B12H?2~ shows the typical reactivity pattern of electrophilic aromatic substitution. The reactivity decreases in the sequence C12 > Br2 > I2 in aqueous or ethanolic solution. It is also reduced with increasing substitution, which is possible, however, up to the very stable perhalogeno ions (e.g., Bi0Cli0~). The apical positions (1,10 and 1,12, respectively) are the most reactive. The positional selectivity increases when less reactive electrophiles are used. Azo coupling is highly representative for its selectivity phenomenon in electrophilic substitution of aromatic compounds. As Hawthorne and Olsen (1964, 1965) found, B10H?0~ (but not B12H?2~) reacts with 4-bromobenzenediazonium tetrafluoroborate. Substitution takes place exclusively in one of the apical positions. We have already discussed azo coupling reactions of borane anions in detail in the book on aromatic diazo compounds (Zollinger, 1994, Sect. 12.11). We also treated the problem of the aromatic character of boranes in that section, since azo-coupling reactions of arenediazonium ions are experimental probes for aromaticity.

1 2-

B

OH

•

H (to be substituted)

Fig. 3-1. Structure of the decahydrodecaborate dianion (3.10) (after Dobrott and Lipscomb, 1962).

104

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

Here, we discuss the diazoboranes. They were discovered in Muetterties' group. In their first paper (Knoth et al., 1964), they described the reaction of the diammonium salt of decahydrodecaborate dianion (3.10) with excess nitrous acid (10-12 equiv.) in aqueous solution (3-16). A brown solid precipitate was obtained that was very difficult to handle because it detonated extremely readily. Yet, it rapidly forms the bisdiazonium inner salt 3.11 when reduced with sodium borohydride. (B10H10)2~ (NH4)2 + HNO2 3/10

** [brown solid] JNaBH4

(3-16)

- (B10H8)2-— 3.11

The decahydrodecaborate dianion (3.10) displays a close, bicapped, Archimedian anti-prismatic framework (Fig. 3-1), confirmed by X-ray crystallography (Dobrott and Lipscomb, 1962). Reactions take place at the apical sites first. Before we discuss the nitrosation - reduction process (3-16), we will refer to the investigation of Spalding's group (Whelan et al., 1982) on the electronic, molecular, and crystal structure of the bisdiazo product (3.11) because it clarified some hitherto open questions. Whelan et al. recorded photoelectron spectra, determined the crystal structure by X-ray analysis, and compared these experimental values with the results of MNDO calculations. The X-ray measurements gave structural data with a residual error index R = 0.43 (for the meaning of R see Sect. 5.1). The molecule has C2 symmetry but shows only slight deviations from the expected D4d, because of the angles N(2) -N(l) -B(l) of 178.7° at the two apical corners, which deviate significantly from 180°. The bond lengths B(1)-N(1) and N(1)-N(2) are 149.9 pm and 109.1 pm, respectively. The NN bond is, therefore, of the same length as in typical arenediazonium salts (see Zollinger 1994, Table 4-1), but is shorter than the bond length in diazomethane (112 pm, see Fig. 5-1 this book). All bond lengths calculated by MNDO agree with the experimental values within 5 pm in the BN2 unit. Considering the complicated type of bonding, this result is noteworthy indeed. The BNN system has calculated charges of -0.34, 0.27, and 0.14, respectively. Summarizing these results, it can be stated that the two functional groups in 3.11 are not classical diazonio groups, rather hybridized diazonio — diazo groups, as symbolized by the mesomeric structure 3.12a-3.12b. Knoth et al. (1964) made some observations with respect to the reaction pathway (3-16). These results were supplemented further in a later paper by Knoth (1966).

3.2 Diazo Derivatives of Polyhedral Boron Hydrides

105

These authors assume that their reaction is similar to the so-called direct introduction of the diazonio group into aromatic compounds that do not contain amino groups. As described by Tedder (1957; see review by Zollinger, 1994, Sect. 2.6), this method is a substitution of carbon-bonded H-atom by a diazonio group and requires the use of 3 equivalents of nitrous acid (see Zollinger, 1994, Schemes 2-35 and 2-36). In the present case, only the first part of Tedder's process can be analogous, namely the nitrosation. The explosive, water-insoluble intermediate and another water-soluble intermediate, mentioned only in Knoth's second paper (1966), as well as the necessity to use a reducing reagent (NaBH4 or zinc and HC1) for the second part, are different. The only further mechanistic information provided by the authors is an IR band of the first (explosive) intermediate at 2380 cm"1, which may be due to an NO+ cation. This information is not sufficient to draw any conclusions on the mechanism for formation of this interesting bisdiazo compound *. The reported yield is 24%. A second method of preparation consists of diazotization of the corresponding diamine 1,10-B10H8(NH2)2~ with nitrosyl chloride in glyme. This route is of no synthetic value, since the diamine is actually prepared from the bisdiazo compound. Knoth (1966) described briefly the synthesis of the diamine as its Tl^ salt by reaction of 3.11 with 100% ammonia at 200 °C in a platinum tube. The diazotization is mentioned by Knoth but not described. In contrast to the 1,10-diaminooctahydrodecaborate itself, the perchlorinated and periodinated derivatives 1,10-B10X8(NH2)2~ (X = Cl or I) can be bis-diazotized with sodium nitrite in mixtures of water, ethanol and acetic acid (Knoth, 1966). In the case of the reaction of l,10-B10Cl8(NH2)i~ Knoth obtained 14% of the monodiazotized compound (N2)B10C18NH3, in addition to the bis-diazo derivative (70%). No experiments are described with the aim of optimizing the monodiazotization. Experience in the diazotization of aromatic diamines (benzene-1,4diamine, 4,4/-diamino-l,l/-diphenyl, etc., see Zollinger, 1994, Sect. 2.6) indicates that selective mono-diazotization of diamino-boranes may also be tricky. l-Monodiazononahydrodecaborate(l—) [1-B10H9(N2)~] can be synthesized by a method of Leyden and Hawthorne (1973, 1975). As mentioned before, decahydrodecaborate(2 —) (3.10) reacts well with one equivalent of an arenediazonium salt to form the 1-phenylazo derivative ArN2HB10H^" (3.13) (Hawthorne and Olsen, 1964, 1965). The tetramethylammonium salt of a protonated phenylazo compound containing electron-withdrawing substituents in the benzene ring (e.g., 2,4,6-Br3 or 4-NO2) is formed in acetonitrile at -35°C. After neutralization at room temperature and workup, the tetramethylammonium salt of the monodiazoborate and the benzene derivative can be isolated (44% yield of 3.14; Scheme 3-17). This method also works if one of the apical positions in the starting material is substituted by a trimethylammonium or a dimethylsulfonium group and the other by a (substituted) phenylazo group. They can also be obtained, however, by the nitrosation —reduction method, as shown by Knoth et al. (1965) for the [l-B10H9S(CH3)2r anion, to yield [1,10-(N2)B10H8S(CH3)2]. * Chemical Abstracts lists this diazoborane as decaborate-, octahydro-, bis(dinitrogen).

106

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

+ ArH

3.13

(3-17)

3.14

The diazonio groups in diazoboranes are interesting for synthetic purposes in the chemistry of the c/oso-borate anions because they may be replaced by nucleophiles. This was shown by Knoth (1966) for the bisdiazoborane 3.11. Leydon and Hawthorne (1975) and Komura et al. (1987) used the monodiazoborane 3.14. Knoth (1966) described the amino-de-diazoniation with NH3 (without solvent at 200 °C under pressure), with pyridine (at reflux), with acetonitrile, followed by hydrolysis to the bisacetylaminoborane B10H8(NH2COCH3)2. With sodium azide it is possible to substitute only one of the diazo groups. Carbonylation leads to the dicarbonylborane B10H8(CO)2 when carried out with carbon monoxide at 140 °C under pressure without solvent. In a solution of cyclohexane at the same temperature, a mixture of B10H8(CO)2, C6H11BioH7(CO)2 and (C6H11)2B10H6(CO)2 was obtained (Knoth, 1985). When the carbonylation was carried out in methane or in benzene, the compounds CH3B10H7(CO)2 and (CH3)2H10H6(CO)2 and C6H5B10H7(CO)2 (two isomers) were identified by GC-MS. The perchlorinated diazoborane 1,10-B10C18(N2)2 reacts analogously. Leydon and Hawthorne (1975) demonstrated that the replacements described by Knoth also apply to the monodiazoborane 3.14. Komura et al. (1987) depicted a synthesis of the 1-thiol B10H9SH2~ (3.15) by reaction of the monodiazoborane 3.14 with A^TV-dimethylthioformamide, followed by alkaline hydrolysis (3-18). Knoth (1972) was able to form a ruthenium complex with a diazenido ligand, using l-(dimethylsulfonio)-10-diazonio(10)-borane. The reaction is described in Scheme 10-13 (Sect. 10.2). Li and Jones (1992) developed a route to diazomethane and carbene derivatives, substituted with o-carboranes, which will be discussed in Section 8.3. H

\ :C-N(CH3)2

[B10H9— N2]~ 3.14

S

= N(CH3)2

B10H9— SKT 3.15

(3-18)

3.3 Addition Products of Dinitrogen to Transition Metal Complexes

107

3.3 Addition Products of Dinitrogen to Transition Metal Complexes Metal -dinitrogen complexes are discussed briefly in this book, because they are structurally related to diazo and diazonium coupounds. In these complexes a diazo group is bonded to a metal and not to a C-atom, as in organic compounds. Addition products of aliphatic and aromatic diazo compounds will be reviewed in Chapter 10. The first indirect evidence for the formation of such complexes is due to Volpin and Shur (1964). They observed that a mixture of an organotitanium compound and a reducing agent absorbs dinitrogen from the gas phase under nonaqueous anaerobic conditions. After the addition of aqueous acid, ammonia was detected. The first dinitrogen complex of a transition metal was discovered by Allen and Senoff (1965). They attempted the synthesis of the hexaamminoruthenium complex [Ru(NH3)6]2+ by the reaction of hydrazine with ruthenium trichloride trihydrate in water, and they found that the dinitrogen complex [Ru(NH3)5(N2)]2+ (3.16) was formed *. The origin of dinitrogen was disproportionation of hydrazine in situ, with simultaneous formation of ammonia (3-19 and 3-20). 3 H2N—NH2

*- N2 + 4 NH3

+ N2

^

[Ru(NH3)5(N2)]2+ + NH3

(3-19)

(3-20)

3.16

Shortly afterwards, Shilov et al. (1966) showed that free N2 can also be taken up as a ligand in Ru11 complexes. The discovery of the first dinitrogen metal complex was, therefore, serendipitous. This fact is rather surprising as it was well known, in 1965, that carbon monoxide, which is isoelectronic with N2, forms a very large number of transition metal complexes. CO complexes had already been well identified with respect to bonding and structure at that time**. Furthermore, it had been known since the 1930's that molybdenum is an essential part of dinitrogen fixation in bacteria and blue-green algae. Nitrogenase enzymes are the major source of fixed nitrogen in nature (see Sect. 3.4). * The ruthenium complex 3.16 contains no metal-carbon bond. By definition, therefore, it is not an organometallic compound. Nevertheless, its synthesis marks the beginning of the organometallic chemistry of dinitrogen and it is the link to the understanding of the chemistry of nitrogen fixation in nature! Was it really necessary to separate organometallic compounds from other metal coordination complexes? We will return to this question in the Epilogue (Chapt. 11). ** It must be mentioned, however, that owing to the higher electronegativity of nitrogen relative to carbon, N2 is a poorer electron donor than CO. The ionization potential of N2 (15.6 eV) is also considerably higher than that of CO (14.0 eV).

108

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

The most likely explanation for the lateness of the discovery of in vitro syntheses of dinitrogen- metal complexes is probably the dominance of the paradigm that N2 is an (almost) inert molecule. The influence of that paradigm (in the sense of Kuhn, 1962) on another scientific discovery was discussed in the book on aromatic diazo compounds (Zollinger, 1994, Chapt. 9). Since the pioneering work of Allen, Senoff, and Shilov et al., dinitrogen complexes have been synthesized with the majority of transition metals. Numerous reviews have been published. Because of the rapidly growing literature, we will only mention summaries published since the mid-1980's (Colquhoun, 1984; Pelikan and Boca, 1984, 1985; Leigh, 1986, 1991; Johnson et al., 1987; Hidai and Mizobe, 1989; Henderson, 1990; Shilov, 1992a; Hidai and Mizobe, 1993). The stabilities of these complexes are highly dependent on the co-ligands. The latter may be ammonia (particularly with Ru and Os), organic phosphines (with Ti, Fe, CO, Ni), halides (with Re, Os, Ir) etc. Electron-rich metals in lower oxidation states, especially 4d and 5 d metals in groups towards the left of the transition series, form the most stable complexes. There are several types of dinitrogen complexes known. In the monohapto * complexes, N2 is bound end-on (3.17). In bridging (binuclear) complexes (3.18), the two N-atoms are located between the two metal atoms. In both types of complex, the NN bond is normally almost as short as an NN triple bond (112-116 pm, N2= 109.76 pm; Davis and Ibers, 1970). Since 1981, binuclear Ta-, W-, and other complexes with diazenido ligands have been analyzed in which the bridging nitrogens are significantly further apart (see Henderson, 1990, Table 1; and below), namely 128-133 pm and more. In these cases, the electron distribution is, therefore, better represented by (3.19). 3.17

LnM—N=N

3.18

LnM—N=N—M'L'n

3.19

LnM=N— N=ML

(M= M' or

Binuclear dinitrogen complexes with two identical metal atoms (called homobinuclear complexes) are obtainable most often by binding N2 at a coordinatively unsaturated metal or by substituting another ligand (e. g., Cl) and forming first a mononuclear dinitrogen complex. This primary product will react with another unsaturated species only if it is more susceptible to attack at the N(/?)-atom. Homobinuclear N2 complexes can also be obtained by coupling of two nitrene-like species formed as transient intermediates in dediazoniation of metal azide complexes (Kane-Maguire et al., 1970), and by coupling of substituted hydrazines (see, e.g., Murray and Schrock, 1985). Within the scope of this book, the method of Ziegler et al. (1976) is interesting, because N2 is transferred by nitrogen exchange from a * The hapticity of a ligand (//) refers to the number of binding sites of the ligand to a metal atom. Bridging N2 to two metals is indicated by ^/-N2.

3.3 Addition Products of Dinitrogen to Transition Metal Complexes

109

diazoalkane (3-21)*. As far as we know, this reaction has not been applied to other cases, nor is it known what product is formed from the (formal) trifluoromethyl carbene. 2[Mn(7/5-C5H5)(CO)2(THF)] + CF3CHN2

» (3 21

CF3CH:

" >

Side-on structures 3.20 are rare. They were found first in matrices, e.g., Co(// 2 -N 2 ) (Ozin and Vander Yoet, 1973) and Fe(// 2 -N 2 )^, x = 1 -5 (Doeff et al., 1984). Bridging side-on dinuclear complexes 3.21 were found and characterized crystallographically by Evans et al. (1988) in a samarium compound in which the NN bond length (108.8 pm) is not significantly different from that of free N2. Quite different NN distances have been found, however, in bridging side-on dinitrogen complexes of zirconium by Fryzuk et al. (1990, 1993). These authors reduced ZrCl3[N(SiMe2-CH2PR2)2] (R = 2-C3H7 and tert-C4H9) with Na-Hg under N2 and obtained the corresponding binuclear dinitrogen complexes [[(R2PCH2 — SiMe 2 ) 2 NH 3 ]ZrCl) 2 (//-A/ 2 :// 2 -N 2 ) of type 3.22**. The NN bond length is 154.9. pm, i.e., longer than the NN single bond in hydrazine. This value clearly indicates that the metal — nitrogen interaction is completely different from that of the binuclear side-on samarium complexes described by Evans et al. 3.20

N LnM—ill N

3.21

N LnM—-IIIHI— MLn N

or

.N l_Xj| N

N

(CH3)2NXN>

Ck\

N(CH3)2

3.23

* /75-C5H5 refers to a cyclopentadienyl anion ligand that is bound to the metal by five C-atoms. ** Formula 3.22 represents the corresponding complex with phosphine ligands PH3.

110

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

In 3.22, one of the Zr d orbitals is unavailable for bonding due to the ancillary tridentate ligand, which positions the amine donor and the chloride to overlap effectively with that d orbital. This explanation is supported by MO calculations. X-Ray structures of related binuclear dinitrogen - Ti end-on complexes, e.g., 3.23 (Beydoun et al. , 1992) support the conclusions of Fryzuk and coworkers. Compound 3.23 has (Z)-disposed neutral amine donors instead of (£>disposed phosphine ligands in 3.22. Three other edge-on bi- and tetranuclear dinitrogen complexes are known (see Fryzuk et al., 1993, structures III-V). X-Ray structures are most informative on bonding in dinitrogen metal complexes. In addition, IR spectra are very useful, particularly on the basis of the NN stretching frequency. End-on complexes of type 3.17 are characterized by a strong NN stretching band in the region 1980-2220 cm"1. The shift of this band to shorter wavenumbers relative to dinitrogen (Raman: 2331 cm"1, Davis and Ibers, 1970) indicates a strong back-donation (see below) in the metal — N (a) bond. The intensities of the NN and CO stretching bands in their corresponding complexes were used at an early date (Darensbourg and Hyde, 1971 ; Darensbourg, 1972; Mason and van Bronswijk, 1971) to assess the degree of electron release from the dn orbitals to the NN and CO p% orbitals, respectively. The stretching of the NN or the CO bond during a vibration increases the importance of the p% bond component. This process corresponds to a flow of electron density from the dn orbitals into the p% orbitals. There is an inverse correlation between the wavenumber and the intensity of the band. N2 complexes with low v(N2) values have high absorption intensities and, therefore, electron donation from the metal to the nitrogens occurs. The intensities of the bands in the corresponding CO complexes are higher. CO is, therefore, both a stronger n acceptor than N2, but also a stronger o donor due to its assymmetric structure. This dn—p% delocalization more than compensates for the electron density donated to the metal (o — rfo* bond) by the lone pair on one of the N-atoms or the C-atom of CO, respectively. This delocalization is called "back donation" or "back bonding". An orbital representation for the bonding in end-on complexes of N2 is given in Figure 3-2. This description is supported by MO calculations performed by the groups of Hoffmann and Fukui (Hoffmann et al., 1977; Yamabe et al., 1980). We will discuss mainly these mononuclear end-on complexes, as they are more closely related to diazo compounds than the binuclear complexes *.

N-N

o- c/a

bond

dn - PK

back donation

Fig. 3-2. Schematic representation of orbital overlap in end-on metal complexes of N2. * For recent theoretical work on binuclear dinitrogen complexes see, e.g., Fryzuk et al., 1993, Blomberg and Siegbahn, 1993 and references given therein.

3.3 Addition Products of Dinitrogen to Transition Metal Complexes

111

The representation of orbital overlap in Figure 3-2 corresponds qualitatively to that in arenediazonium ions, as discussed in our book on aromatic diazo compounds (Sects. 8.3 and 8.4): the C —N o bond in Ar-N/is also stabilized by n electron donation from the pn orbitals of the aryl group to the diazonio group. There is, however, an important difference with respect to the magnitude of the back donation in metal complexes of N2 relative to the bonding of the diazonio group in arenediazonium ions: The latter are electrophiles, the N(/?)-atom being attacked by nucleophiles (see Zollinger, 1994, Chapts. 7 and 8). In most cases, N2 —metal complexes are nucleophilic, due to very strong back donation. For example, complexes of Mo and W add one or two protons at the N(/?)-atom (Chatt et al., 1974; Heath et al., 1974; Hidai et al., 1976a ; Colquhoun, 1984; Shilov, 1992a; Leigh, 1992). Protonation has been intensively investigated, because it is likely to be the first step in biological fixation after formation of an N2 complex (Sect. 3.4). Dinitrogen-metal complexes can also act as simple donors to Lewis acids like A1C13 or A1(CH3)3 (Donovan-Mtunzi et al., 1985, and references therein). In the context of general diazo chemistry the investigation of Hidai's group (Ishii et al., 1992a) of the anionic dinitrogen-tungsten complex 3.24 [P-P = dppe = (C6H5)2PCH2CH2P(C6H5)2] in the reaction with methyl 4-fluoro-benzoate, coordinated with tricarbonyl-chromium, is particularly interesting. Strong back donation from the anionic tungsten center to coordinated dinitrogen leads to the nucleophilic substitution of fluoride ion and the formation of a compound with a phenylazo group. This process may be called a nucleophilic azo-coupling reaction! * It should not, however, be characterized as a ("semiaromatic") azo compound, as it has a relatively long NN bond (131.4 pm). It is important to note that the reaction does not take place with the uncoordinated 4-fluoro-benzoate. Nucleophilic attack at the /?-nitrogen is, however, also possible, but only with very strong nucleophiles. Treatment of the complex [Mn(//5-C5H5)(CO)2(N2)] with phenyllithium and quenching with acid gives the phenyldiazenido complex [Mn[^5-C5H5)(CO)2(NrC6H5)]- (Sellmann and Weiss, 1978).

(CO)3Crx

/=)

N COOCHg

N

-^

II

0-22)

N C

3-24

•

'

g

s * A similar case is discussed in Sect. 3.4 (Reaction of the N2-Mo complex of the crown thioether 3.27 with methyl bromide).

112

5 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

Armor and Taube (1970) investigated the N(a), N(/?) rearrangement of the two Natoms in the (pentaammino)diazenidoruthenium complex ion 3.16. Interesting similarities to the corresponding rearrangement of the arenediazonium ions (see Zollinger 1994, Sect. 8.3, p. 171) are shown. The enthalpy of activation of the rearrangement in 3.16 is 88 kJ mol"1 and the enthalpy of activation for the loss of N2 is 117 kJ mol"1. Thus, the rearrangement proceeds via an intermediate that is only about 29 kJ mol"1 lower in energy than that required for complete dissociation. This result may indicate a side-on bonded intermediate similar in structure to the tight ion-molecule pair suggested by Zollinger's group (Hashida et al., 1978, and Maurer et al., 1979) for the two-step dediazoniation of arenediazonium ions. The dinitrogen ligand can be replaced by other ligands. An interesting case was found by Perthuisot and Jones (1994): In the complex Fe(depe)2N2 (depe = l,2-bis(diethylphosphino)-ethane) N2 is replaced irreversibly by ligands like CO, H2, ethyne, etc. Particularly interesting is the ready reaction at the CH2 group of 2-methylstyrene, forming HFe(depe)2(CH = CHC6H4CH3). Summarizing the general discussion on the coordination of dinitrogen with transition metals, we draw attention to a review of Togni and Venanzi on "nitrogen donors in organometallic chemistry and homogenous catalysis" (1994). They start their review with the statement that textbooks on organometallic chemistry and homogeneous catalysis make sporadic reference to the use of N-donors as ligands, but that hitherto no attempt has been made to examine their role systematically, as has been done for P-donors. It goes without saying that Togni and Venanzi's systematization is based predominantly on amines as N-donors. Neither dinitrogen nor diazo compounds are included in the review. I have full understanding for not discussing these two types of N-ligands. On the basis of the fundamental principle of coordination as a reaction of transition metals, i. e., Lewis acids, with ligands, i. e., Lewis bases, one would not expect dinitrogen or diazo compounds to form coordination complexes with metals at all — but they do! We may speculate on that dichotomy: We see first a correlation to the theoretical work of Glaser's group (Glaser and Choy, 1991; Glaser et al., 1992b; Horan and Glaser, 1994; Glaser and Horan, 1995; and further papers, discussed in Sect. 5.3 of this book). Glaser investigated on a comparative basis ten different inorganic, aliphatic, and aromatic diazonium ions and, in addition, the methanediazonium ion with 14 sets of theoretical approaches. Electron density analysis has revealed that the overall charge of the diazonio group is, in most cases, small (see Table 5-3). In a nut shell Glaser et al. (1992b, p. 998) say "that the cations force N2 to form diazonium ions". Isn't that also the case for metal ions? Second, back donation was shown by various authors (see earlier in this section) to be important for coordination compounds, and, by a dual substituent parameter treatment, for the stability of arenediazonium ions (Zollinger, 1990, 1994, p. 168 ff.). Further work is necessary to bring these speculations to a systematization of dinitrogen and diazenido coordination chemistry (see also the Epilogue, Chapt. 11)! In the context of this book, investigations on the reactions of nitrosyl ruthenium complexes with aromatic and aliphatic primary amines are interesting, as they permit conclusions on the relative stabilities of bonds between dinitrogen and Ru11, aryl

3.3 Addition Products of Dinitrogen to Transition Metal Complexes

113

and alkyl cations. Guengerich and Schug (1978) found that the (pentaammino)(nitrosyl) ruthenium(n) complex in (3-23) forms the rutheniumpentaammino-dinitrogen complex in the reaction with primary aliphatic amines. In analogy to some synthetic methods used for organic diazo compounds (see Sects. 2.6-2.8, and Zollinger, 1994, Sect. 2.4), this reaction may be called a diazo transfer. The (bipyridine)(nitrosyl)(chloro) ruthenium(n) complex in (3-24) reacts, however, with an aromatic amine to form an aryldiazenido complex, as found by Bowden et al. (1973, 1977). This latter reaction demonstrates clearly that nitrosyl ruthenium complexes are nitrosating reagents. It is, therefore, likely that the primary product in the first-mentioned reaction is an alkyldiazenido complex. We conclude from these two reactions that the Ru11 —N bond in the dinitrogen-Ru complex is stronger than the N-C sp 2 bond in the alkyldiazenido-Ru complex, but weaker than the N-C sp 2 bond in the aryldiazenido-Ru complex. This complex is able to deliver an arenediazonium ion, as shown by the azo coupling reaction in Scheme (3-25). Ru[NH3]5NO*- + 2 RNH2 —*—*~

Ru[bipy]2[No]ci2+ + ArNH2

Ru[NH3]5N22+ + ROM + RNH3+

(3-23)

Ru[bipy]2[N2Ar]ci2+ + H2O

(3-24)

—>—>-

Ru[bipy]2[N2Ar]d2+

(3-25) r^^T^^V" Ru[bipy]2[OH] Cl

As mentioned above, bridging (or binuclear) N2 complexes of type 3.18 and 3.19 are formally not related to organic diazonium or diazo compounds, but to azo compounds. It must be emphasized, however, that, with respect to the NN bond lengths, binuclear complexes of type 3.19 only have a similarity to azo compounds, but in the majority (3.18) the bond lengths are almost the same as those of aromatic diazonium ions (see above). In both types of homobinuclear complexes, the three bonds M—-N—'N—-M are collinear*. The vibrational frequency of the NN bond is much smaller (1660 cm"1) than in end-on N2 complexes (see above), but closer to that of the corresponding frequency of azo compounds like azomethane (Kahovek et al., 1937, 1938) and azobenzene (Stammreich, 1950)** or (£>arenediazocyanides (1390-1450 cm"1, Ignasiak et al., 1975). Ta and W bridging complexes, for which * The corresponding bridging complexes with CO are not collinear. ** v (Raman) = 1442 cm"1 is reported for azomethane and for azobenzene.

114

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

Churchill and Wasserman (1982) and Churchill et al. (1984), respectively, published X-ray data, have analogous structures with M-N—N angles between 175.6° and 178.9° and NN distances of 128 to 129 pm (see also Murray and Schrode, 1985). Correlations of additions of dinitrogen to transition metal complexes, to carbenes, and to aryl cations have been discussed by Yamabe et al. (1980), by Grieve et al. (1985) and by Zollinger (1983, 1990): arenediazonium ions and diazoalkanes as ligands for transition metals are discussed in Chapter 10. It is interesting to mention in the context of this section that transition metal complexes with aryl- and alkyldiazenido ligands can be formed, in part in good yield, by N(/?)-arylations and N(/?)-alkylations, respectively, of the corresponding end-on dinitrogen complexes (see examples in Sects. 3.3 and 10.3, respectively).

3.4 Short Review on the Chemistry of Nitrogen Fixation All biochemical work on biological fixation of dinitrogen conducted during the last three decades strongly indicates that the formation of dinitrogen addition products with metal-complex enzymes and the low-temperature reduction of their dinitrogen ligand occupy a key position in that process. As free-living organisms, only very primitive bacteria and blue-green algae are able to fix nitrogen. Symbiotic microorganisms, e.g., rhizobium, are more important. They live in the soil and enter the root hairs of various species of legumes (beans, peas, etc.), infecting certain cells and causing the formation of characteristic nodules. Only after this nodulation can they fix nitrogen and provide the plant with ammonia in exchange for carbohydrates. The efficiency for N2 is very high and decreases only if the nitrogen partial pressure is lower than about a tenth of that in the atmosphere. Energetically, however, the formation of ammonia is quite inefficient, as the consumption of 1 g glucose only results in the production of ca. 18 mg NH 3 . Since 1930, it has been known that molybdenum is closely associated with the metabolism of N2. Vanadium is used by cultures of some bacteria in place of Mo (review: Eady, 1990) and a nitrogenase containing iron only was found by Bishop's group (Chiswell et al., 1988). Modern biochemical research on nitrogenases, the group of enzymes responsible for nitrogen fixation, was initiated in 1960, when nitrogenase from Clostridium pasteuricum was first extracted in active form by Carnahan et al. (1960). As soon as the enzyme comes into contact with atmospheric oxygen, it loses its activity. Nitrogen fixation works, therefore, only under anaerobic conditions. The enzymology and biochemistry of nitrogenases started only a few years before the first dinitrogen metal complex was discovered by Allen and Senoff in 1965. Cooperation and mutual encouragement increased when more and more results were found on both sides. Two iron-sulfur proteins are involved in the nitrogenase complex. The larger protein, the nitrogenase itself, consists of four subunits and has an

3.4 Short Review on the Chemistry of Nitrogen Fixation

115

overall molecular mass of 220000-240000 daltons (g mol"1). The protein has two Mo atoms and about thirty atoms each of Fe and S. Homocitric acid was found to be an endogenous ligand and to be essential for the biosynthesis. These clusters are strongly implicated as the substrate-binding sites. They are called iron molybdenum cofactor (FeMoco; review: Burgess, 1990; Evans et al., 1993), but the binding mode of N2 is not yet clear. The two FeMoco clusters are probably adjacent to about 700 pm. The smaller protein has a molecular mass of 60000-70000 daltons. Extended X-ray absorption fine structure (EXAFS) studies show that it includes a single Fe4S4 cubane cluster (P-cluster) similar to that in ferredoxins, which are important for various electron transport chains in living organisms. The smaller protein in the nitrogenase system is a strongly reductive reductase that is obviously responsible for the transfer of electrons to the larger protein. Various X-ray structures determined since 1985 (Tsuprun et al., 1985; Sosfenov et al., 1986; Moffat, 1990; Bolin et al., 1991; Georgiadis et al., 1992; Kim and Rees, 1992a, 1992b; discussion: Sellmann, 1993) demonstrate the improvement in accuracy of models for the active site of FeMoco in nitrogenase in Azotobacter vinelandii. As shown in Figure 3-3, the model constructed on the basis of Kim and Rees' results shows a slightly distorted double cubane structure, one with three Fe atoms and one Mo atom with the homocitrate ligand, the other with four Fe atoms. The two cubane-like entities are combined by two sulfur bridges and a crosslinking ligand of unknown structure (X). The P cluster also consists of two bridged 4 Fe:4 S cubanes cross-linked by two cysteine thiol ligands. The significance of the work of Kim and Rees for science in general is evident from the fact that in the book Chemistry Imagined, written by Roald Hoffmann, in a unique collaboration with artist Vivian Torrence (1993), nitrogen fixation and, in particular, the structure of the active site of FeMoco in nitrogenase (Fig. 3-3) is the subject of a particular essay. It seems fairly certain that the formation of ammonia in nitrogen fixation is based on four processes or groups of processes, namely (1) formation of a dinitro-

N(his) X = unknown ligand

Fig. 3-3. Model for the active site of FeMo-cofactor in nitrogenase (after Reedijk, 1993, p. 471; based on the X-ray investigation of Kim and Rees, 1992 a, 1992 b).

116

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

gen-metal complex, (2) one or more nitrogen protonations, (3) electron transfer processes, i. e., reduction, and (4) dissociation of the NN bond. From our knowledge on structure and reactivity of the dinitrogen molecule, e. g., the very high dissociation energy of the triple bond (940 kJ mol"1), it is obvious that the major problem is not the formation of the diazenido complex (1), but the consecutive steps (2)-(4). In particular, it is unlikely that diazene (HN=NH) is an intermediate, as it is thermodynamically very unfavorable. Chemical research on nitrogen fixation concentrated, therefore, in recent years on reduction mechanisms of dinitrogen complexes (see review of Shilov, 1992). Investigations on model systems have been conducted for all these processes. There is no doubt that results from such models will one day form a good basis for understanding the mechanism of enzymatic nitrogen fixation. For the dinitrogen-metal complex either a mono- or binuclear complex (see Sect. 3.3) must be considered. Both types are well-known, and protonation has been investigated (mononuclear complexes: Henderson et al., 1983, 1989; Shilov, 1992, and references therein; binuclear complexes: Dilworth et al., 1990; Henderson et al., 1990; Henderson and Morgan, 1990; Shilov, 1992; Blomberg and Siegbahn, 1993)*. In a review, Henderson (1990) illustrated the range of binuclear species that contain nitrogenous residues from the mono- to the tetra-protonated forms. Among the systems studied are not only transition metal complexes with organic ligands, but also apparently simple inorganic metal compounds: quite frequently, heterogenous systems based on co-precipitation of mixed metal hydroxides of Cr11, V11, Ti11, Nbm, and Tam give good yields of hydrazine at high pH, or ammonia at low pH, particularly in the presence of Mg ions (see summaries by Shilov, 1987, and by Henderson et al., 1983). An example is the sequence of reactions (3-26). In the protonation step, V11 changes into Vm. There are also investigations using binuclear dinitrogen-divanadium model complexes with organic ligands (e.g., 2,4,6-trimethylphenyl by Floriani's group: Ferguson et al., 1993). A well-known system that simulates nitrogenase was developed at a relatively early time by Schrauzer (1975). The Mo source is an alkali metal molybdate as complex with (H-)-L-cystein to simulate the sulfur ligand 3.25, a salt of the complex Fe4S4-cubane type anion [Fe4S4(SR)4]2~ (3.26) as a model for the P-cluster in nitrogenase, and disodium dithionite (Na2S2O4) as reducing agent. In alkaline solution (pH 7-10), this system indeed produces ammonia from dinitrogen, but with an efficiency about 1000 times lower than that of nitrogenase in vitro. The overall reaction in Schrauzer's system corresponds to that of nitrogenase (3-27). An interesting later development of Schrauzer's 4 Fe: 4 S cluster 3.26 was accomplished by Yoshida et al. (1988). These authors showed that the 16-membered quadridentate crown thioether 3.27 (3,3,7,7,ll,ll,15,15-octamethyl-l,5,9,13-tetrathiocyclohexadecane, Me8[16]aneS4) forms a dinitrogen-molybdenum(O) complex easily (5 atm N2). The observation of Yoshida and coworkers that this complex can be

* There are several other references on the chemistry of nitrogen reduction in model complexes and on the biochemistry with nitrogenases.

3.4 Short Review on the Chemistry of Nitrogen Fixation

111

H N=N

>

^u\

JkT + H+ -4-o^ // ^-O^ L yOfl ^— u _> ""sS VL>CI

V:

CX

M Mg

Mg

/O

(3-26)

NH3

SR

RS 3.25

3.26

\

3.27

methylated with methyl bromide at the two N(/?)-atoms is also interesting in the context of our discussion of the nucleophilicity of N2 complexes in Section 3.3 (Scheme 3-22). A completely different system was developed by Shilov and coworkers (Didenko et al., 1983 and Russian references therein): they used a vessel containing sodium amalgam, apparently coated with the phospholipid phosphatidylcholine (lecithin). Molybdenum is added as MoCl5 to methanol as solvent. The results indicate that two Mom ions are involved in the reduction of each N2 molecule. The reaction proN2 + 8 e" + 8 H+

*»

2 NH3 + H2

(3-27)

118

3 Inorganic Diazo Compounds and Metal Complexes with Dinitrogen as Ligand

ceeds at 1 atm N2 pressure and room temperature. The main product is hydrazine, but some ammonia is also formed. It is assumed that the amalgam is coated with the lecithin so that the positive ionic head is directed to the amalgam surface and the hydrophobic tail to the solution; thus, protecting the amalgam against hydrolytic decomposition. This system demonstrates a fundamental problem of nitrogen fixation: any system must supply at least six hydrogen atoms for ammonia formation from one molecule of N2 (neglecting for a moment that the natural process also forms one equivalent of H2, see Scheme 3-27). A sufficiently high reducing potential is necessary, but — in an aqueous system — without reducing mainly H2O to H2!)*. It is known that nitrogenase reduces ethyne (acetylene) to ethene and ethane**. This is also the case for Schrauzer's system mentioned above. Schrauzer (1975) tested his process with diazene, which may be an intermediate in the reduction of dinitrogen (see, however, the remark about diazene made earlier). Diazene decomposed, however, to hydrazine, following Scheme 3-28. The experiment neither supports nor contradicts the hypothesis of the intermediacy of diazene in nitrogen fixation, because it is known that hydrazine is reduced to ammonia if added to the natural nitrogenase system. 3 HN=NH

^

2 N2 + H2 + H2N—NH2

(3-28)

A more detailed review of the biochemistry of nitrogenase is not within the scope of this book. There are many reviews and books on this subject, e.g., those written by Stewart and Rowell (1986), Shilov (1987, 1992b), Gallon and Chaplin (1988), Gresshoff et al. (1990), Burgess (1991), Smith and Eady (1992). There are also books on molybdenum enzymes (e. g., Spiro, 1985). Most reviews mentioned earlier in this section and in Section 3.3 contain short outlines of recent progress in the biochemistry of nitrogenase. A short general comment seems to be appropriate at the end of this section. Nitrogen fixation research is a fascinating example of truly multidisciplinary work on a genuine biological problem. In spite of efforts from inorganic, organic, and physical chemistry, from crystallography, biochemistry, and biology, we are still relatively far away from a satisfactory level of understanding. The problem has, however, yet another aspect: at the end of the last century, European and North American civilization realized that the supply of Chilean saltpeter would eventually come to an end, and that this would probably lead to famine. Search for a new source for nitrogenous fertilizers was a challenge for the chemists. That problem was solved shortly before the first world war by Haber and Bosch in Germany. The Haber-Bosch process was indeed extremely welcome, but even look-

* It is clear that neither Schrauzer nor Shilov had the intention to include this problem in their models, as their reducing reagents are not regenerated in those model processes. ** Nitrogenase also reduces nitrous oxide (N2O), cyclopentene, and methylisocyanide (CH3NC).

3.4 Short Review on the Chemistry of Nitrogen Fixation

119

ing at it superficially, the dominant problem of N2 chemistry is also evident: The Haber-Bosch process works under extremely vigorous reaction conditions, necessary because of the low reactivity of N2! That did and still does not matter as long as energy and hydrogen are available at the present prices. That will, however, probably change in the future, when hydrogen must be obtained from water, and not from methane and mineral oil as at present. By that time, a large-scale process using transition-metal catalysts may have been found, but the major economic and energy problem will still be the reduction of nitrogen — or the interdisciplinary research of microbiologists, genetic engineers, and chemists will achieve a technologically feasible bioengineering process for nitrogen fixation. This could be new types of microorganisms for nitrogen fixation, which may, after appropriate genetic engineering, have higher rates of nitrogen turnover. They may be used in combination with selected strains of leguminosae, say one season in five years, to supply nitrogenous material as natural fertilizer to the soil for the following four years. These are long-range problems that we have to consider, although they are only very marginally related to the content and aim of this book!

4 Kinetics and Mechanism of Aliphatic Diazotization

4.1 Nitrosation of Alkylamines The diazotization mechanism of primary aliphatic amines has been investigated relatively little. The obvious reason is the fact that alkanediazonium ions are, in general, not stable (see Sect. 2.1). Their instability is, however, not a justification against kinetic measurements as it is likely that, experimentally, the decrease in concentration of either one of the reagents, amine or nitrosating reagent, or the amount of N2 found, could be followed as a function of time. In analogy to the diazotization kinetics of aromatic amines, formation of the N — N bond, i. e., the nitrosation step of diazotization, is also rate-determining if primary aliphatic amines are used as reagents. As early as 1937, Schmid and Muhr stated that identical kinetics should govern the diazotization of aromatic and aliphatic amines. There is an early and remarkable exception, however, to the paucity of investigations on the diazotization mechanism of aliphatic amines. Taylor (1928; Taylor and Price, 1929) examined the rate of diazotization of alkylamines, as well as that of the decomposition of ammonium nitrite. Taylor found the rate to be always proportional to the concentration of amine, but dependent on the square of the concentration of nitrite. This unexpected kinetic influence of the nitrosating reagent remained unnoticed, however, for a long time. It was explained correctly only by Ingold's group more than 20 years later (Hughes et al., 1950) by the postulate that, in aromatic diazotizations, N2O3 is the nitrosating reagent under the specific reaction conditions (see review: Zollinger, 1994, Sect. 3.1). It is, therefore, not surprising that, apart from Taylor's observation of the rate dependence on the square of the nitrite concentration, the other major type of kinetics, namely a rate proportionality to [HNO2][H+] — consistent with the nitrosyl ion (NO + ) or the nitrosoacidium ion (H 2 O—NO + ) as reagent — is also dominant for diazotization of aliphatic amines. Such conscientious and detailed investigations as those of Ridd's group undertaken with aromatic amines in order to determine reactive forms in aromatic diazotizations (see Zollinger, 1994, Sect. 3.2) have, however, never been conducted with aliphatic amines*. Nevertheless, it is known that the pH range 3-5 is, in general, optimal for the fast rates and high yields in diazotization of aliphatic amines. * See, however, the results of Hovinen and Fishbein (1992, also Hovinen et al., 1992) on the deamination mechanism of methylamine (see Sect. 7.2) and the kinetic investigations made at the University of Santiago de Compostela (Spain) in this Section (Casado et al., 1981 a-1985b). Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

122

4 Kinetics and Mechanism of Aliphatic Diazotization

Secondary aliphatic amines form stable 7V-nitrosoamines, however, and therefore, their investigation will be discussed briefly in this section, although 7V-nitroso derivatives of secondary aliphatic amines do not fall within the scope of this book. We will see that kinetics and mechanisms of nitrosation of secondary amines display many similarities with the diazotization of primary aromatic amines. Casado et al. (1983 c) studied the nitrosation kinetics of diethyl-, 1,1'- and 2,2'-dipropyl-, l,l'-and 2,2'-dibutyl-, benzylmethyl-, benzylethyl- and cyclohexyl(methyl)amine under conditions used for the classical measurements with aromatic amines by Ridd in Ingold's school 25 years before (Hughes et al., 1958; Hughes and Ridd, 1958) and which had been already used by Taylor (1928) as mentioned above. Casado et al. (1983 c) found the same second-order rate dependence on nitrous acid concentration involving, therefore, dinitrogen trioxide as the reactive species. With all the amines mentioned, rate constants for the nitrosating step (N2O3 + R2NH) were of the order of 108 M -1 s"1, a value that is fairly close to the calculated limit of 7 x 109 M"1 s"1 for encounter-controlled reaction (Schmoluchowski, 1917; see also Zollinger, 1994, Sect. 3.3). The low enthalpies of activation (10-20 kJ mol"1) found by Casado et al., also indicate such a process. Under slightly more acidic conditions, Casado et al. (1981 a, 1985 a) identified, in addition to the quadratic term, a linear term with respect to the concentration of the nitrosating reagent. This result is in line with investigations on the kinetics of aromatic diazotization. The linear term is consistent with NO+ (or H2NO^) as electrophilic species. Furthermore, Castro et al. (1986 a) investigated the nitrosation of the secondary aliphatic amines in aqueous acidic solution in the presence of bromide ions. As expected for these reaction conditions, two kinetic terms were obtained, one second- and one first-order with respect to the electrophile, corresponding to N2O3 and NOBr, respectively. The intrinsic rate constants for attack of NOBr on the amines (0.7-5.0 x 107 M"1 s"1) are lower than expected for diffusion control by about two powers of ten or more and about 50-100 times slower than that of the reaction of NOBr with the aniline derivatives (see the summary by Ridd, 1978). As a tentative explanation, the authors consider that NOBr-amine encounter pairs may be formed when there are n orbitals in the amine, and that encounter pair formation is less favored when no such orbital is present. It must also be emphasized, however, that these calculations of intrinsic rate constants for the reaction step ONX + R2NH (X = ONO or halogens) are directly dependent on the numerical value of the equilibrium constants Ko^x- The accurate determination of these constants is experimentally difficult, as shown for ^fN2o3: earlier measurements by Stedman (1979) gave a value of ca. 2.1 x 10"1 M -1, whereas more recent determinations resulted in #N2o3 = 3.0 x 10~3 M -1 (Markovits et al., 1981). Catalysis by other nucleophiles has also been found for secondary aliphatic amines, e. g., by thiocyanate (Fan and Tannenbaum, 1973), and by thiourea and its tetramethyl derivative (Meyer and Williams, 1988, and earlier investigations mentioned there). The results are comparable to those of aromatic diazotizations (Zollinger, 1994, Sect. 3.3). The rate of nitrosation of long-chain amines increases if the critical micelle concentration is exceeded (Moss et al., 1973a).

4.1 Nitrosation of Alkylamines

123

The nitrosation of a-amino acids is especially interesting because of the biological importance of 7V-nitrosoamines (see Sect. 4.2). The nitrosation mechanism was investigated first with amino acids containing a secondary amino group, namely proline (4.1, X = H), 4-hydroxyproline (4.1, X = OH), and sarcosine (4.2), but also with cysteine (4.3).

H3C — NH-CH2-COOH

/CH2SH H2N-Ch/

4.2

4.3

Earlier mechanistic studies by Mirvish et al. (1973, review 1975) and others were followed more recently by detailed kinetic and spectroscopic investigations by Casado et al. (1985 a), by Meyer and Williams (1988), Patel and Williams (1989,1990) and Oh and Williams (1989). The nitrosation mechanism of the amino acids is rendered more complex due to the presence of other groups that can also be nitrosated. It seems to be a general phenomenon that, besides direct 7V-nitrosation, the 7V-nitroso compound is also formed in a parallel reaction, in which a slow intramolecular rearrangement (e. g., 4.4) follows the attack of the nitrosyl ion on the carboxylate group of the amino acid. In the case of cysteine, primary 5-nitrosation of the thiolate anion can be observed. Considering the high nucleophilicity of the sulfur atom, this effect is not surprising. O-Nitrosation at the hydroxy group of hydroxyproline has also been observed.

H

7VCO 4.4

The nitrosation of amides is related to that of a-amino acids in as much as the amino group of an amide is directly bonded to a carbonyl C-atom, but not to a methylene or methine group (CH2 or CHR) adjacent to a carboxyl group. As expected on the basis of the lower nucleophilicity of the amide N-atom, nitrosation of amides is slower than that of a-amino acids. Nevertheless, nitrosation of amides is sufficiently fast that such reactions can be used as scavengers of excess nitrous acid employed in diazotizations. As discussed in Volume 1 (1994, p. 12), the classical reagent for that purpose is urea, because its nitrosation yields, obviously through a very unstable diazonium intermediate, only gaseous products (CO2 and N2) besides water (see Zollinger, 1994, Scheme 2-2, p. 13). More recently, urea has often been replaced by sulfamic acid (H2N-SO3H) due to its faster reaction. Williams' group

124

4 Kinetics and Mechanism of Aliphatic Diazotization

(Fitzpatrick et al., 1984) investigated the kinetics of these two and seven other nitrous acid scavengers. The reaction kinetics of the addition of the nitrosyl cation to phenylurea have been studied by Casado's group (Meijide et al., 1987). There is evidence for an initial O-nitrosation step followed by two competitive rearrangements of the nitroso groups to the two N-atoms of the ureido part. One of the N-nitroso compounds formed may be converted into the benzenediazonium ion. Meijide et al. assume, however, that the O-nitroso intermediate leads directly to the benzenediazonium ion (4-1). NO ff N0++ H5C6—NH—C—NH2

<

»

ff H5C6—NH—C —NH2

H5C6N2+

(4-1)

With respect to mechanistic investigations of amide nitrosation, it was found only relatively recently that the mechanism is different from that of amines. These investigations started with observations of Berry and Challis (1974), who did not detect any nucleophilic catalysis. This result became understandable when two groups (Hallett and Williams, 1980; Snyder and Stock, 1980) independently found that the nitrosation of amides showed the features of general base catalysis due to a ratelimiting proton transfer from the initially rapidly and reversibly formed 7V-nitroso amide, and not a rate-limiting attack by the nitrosation reagent. As a consequence, the amide nitrosation also shows a primary kinetic isotope effect (Casado et al., 1983a, 1984b). A detailed kinetic investigation (Castro et al., 1986b) demonstrated that the slopes and curvature of Br0nsted plots of the general base catalysis are not consistent with 7V-nitrosation but rather with O-nitrosation followed by an O,N rearrangement of the nitroso group (4-2). Base catalysis is based on the O-nitroso cation in (4-2) being a steady-state intermediate and the inequality k-\ [X~] >&2[B] in (4-3). This relationship is more likely to be the case for amides than for amines, because of the presence of a carbonyl group at the amino group. Peptides can also be nitrosated, primarily at the terminal and side-chain amino groups. This is a method for the determination of the number of primary amino groups in peptides. In addition, amide groups in the chain can also be nitrosated. It has been shown (Garcia et al., 1984) that nitrogen oxides give mono- and dinitroso derivatives with some dipeptides. As nitrogen oxides are present in modern urban atmospheres, this result has implications with respect to the potential carcinogenicity of TV-nitroso compounds (see Sect. 4.2). The nitrosation mechanism of aliphatic amines by metal nitrosyl complexes was studied with various secondary amines and one primary amine (ethylamine) using pentacyanonitrosylferrate (sodium nitroprusside). Very little mechanistic information is available for reactions with other metal nitrosyl complexes (see also Sects. 2.3, 4.3, and 7.2).

4.1 Nitrosation of Alkylamines

125

(4-2)

^ _

C— N \

*

>

V

\ DO

, u+ ~"~R on

"S, Jr

*' The nitrosation of primary alkylamines leads to deamination products. Hungarian chemists (Dozsa et al, 1984; Katho et al., 1984; Katho and Beck, 1988) investigated the kinetics by spectrophotometry and by N2-volumetric measurements in aqueous solution at pH 8.6-10.2. The results are consistent with the mechanism (4-4), in which an alkyldiazenido-iron complex 4.5 is formed followed by its decomposition to the dinitrogen-iron complex 4.6 by attack of hydroxyl ions. In the opinion of the present author, however, there are other mechanisms that would also support the kinetic data. Mechanistic investigations of Casado et al. (1983 b, 1985 b) and Butler et al. (1984) with secondary alkylamines show that the rates of these nitrosations are of firstorder in the concentration of nitroprusside ion and of first- or second-order in the amine concentration. Normally, both terms are present but, sometimes, depending

[(CN)5Fe—NO]2"

(CN)5Fe—N

+ H2NR

X

NH2R

-H20

r(CN)5Fe-N2l3- « + °^ L

-J

4.6 -N 2 | + H 2 0

[Fe(CN)5H2o]3"

— ROH

[(CN)5Fe-N2— R]S L

J

4.5

126

4 Kinetics and Mechanism of Aliphatic Diazotization

on the amine structure and on the experimental conditions, the first- or the secondorder term can dominate. Furthermore, the hydrolysis of nitroprusside ion can be a competitive reaction at high basicity (see Scheme 2-15). Reactions were usually conducted in buffers in the pH range 11-13. As shown in Schemes (4-5)-(4-7), a weak addition complex (low constant K) of the amine with the nitroprusside ion (probably to the nitroso nitrogen atom) is formed first. In both of the two following competitive dissociations of this complex, the Af-nitrosoamine is formed. In (4-6), a second amine molecule and in (4-7) water replaces the nitrosyl ligand at the sixth coordination site of the iron ion. With ethylamine, the primary nitrosoamine forms the diazonium ion, which decomposes rapidly to give ethanol and N2 (Butler et al., 1984).

Fe(CN)5N02- + R2NH

Or Fe(CN)5N

+

Fe(CN)5N(+ NHR2J

l2+ R2NH

(4-5)

s w

'°

»

Fe(CN)5NR2H3- + R2NNO + H+

(4-6)

S W

>

Fe(CN)5H2O3- + R2NNO + H+

(4-7)

NHR2J

Or

I2-

Fe(CN)5N

+ H20

'°

NHR2J

Product distribution in alkaline nitrosations with nitroprusside ion is significantly different from that in acidic solution (McGarvie and Kimura, 1986; see Sect. 7.4). A mechanistically different type of nitrosation was discovered by Keefer and Roller (1973), namely a nitrosation of secondary aliphatic amines with nitrite anions in alkaline solution, catalyzed by aldehydes. Although it is unlikely to be applicable to diazotization, i. e., to primary amines, it will be mentioned here because it is a good example of the fact that, in chemistry, particularly in organic chemistry, for a certain type of reaction, e. g., nitroso-de-protonation (which includes substitution of protons bonded to C, N, O, S, etc., atoms), practically all methods follow the same basic pattern (in the case of nitrosation substitution by an electrophilic nitrosating reagent). The Keefer-Roller nitrosation is apparently different if one looks at the stoichiometric equation (4-8). A careful kinetic investigation (Casado et al., 1981 b, 1984 a) on the concentration and pH dependence of this reaction revealed that the nitrite anion and free amine base enter the substitution process and that formaldehyde is a true catalyst, as it is not required in equimolar amounts. CH20 R2NH + ONCT

(Cat }

' >

R2N—NO + OhT

(4-8)

4.2 Carcinogenicity of N-Nitrosoamines

127

One might, therefore, conclude that this is an example of a general principle in modern organic synthesis, discovered by Corey and by Seebach, called symmetrization of reactivity (Corey, 1967) or, more commonly, Umpolung* (Seebach, 1969, 1979; Seebach and Enders, 1975; Hase, 1987). Generally speaking, it refers, for example, to addition of a nucleophile Nu 5 ~ to an electrophile E 5+ , in which the 8's indicate that the charge may be a fraction of unit charges only. In such reactions involving a reversal of the normal polarity ("Umpolung"), the two reagents are changed in such a way that one or both change their nature, i. e., the electrophile becomes the nucleophile, but the products are still the same. The Keefer-Roller nitrosation is not such as case, however, if one includes the mechanistic role of the catalyst, as shown in the sequence given in (4-9, R7 = H for formaldehyde). The aldehyde reacts first with the amine, forming an iminium ion. The Hard and Soft Acid and Base principle of Pearson (1963, 1968; Parr and Pearson, 1983; see also Zollinger, 1994, Sect. 3.2) predicts that the reaction of one of the O-atoms of the nitrite ion with the aldehyde C-atom of the iminium ion is the most likely reaction. In the last step, this addition product rearranges through an NN bonded four-membered ring transition state or intermediate into the nitrosoamine and the aldehyde. This mechanism is consistent with Casado's kinetic results. OH

R2NH + R'CHO

I (4-9)

t

R2NNO + R'CHO

4.2 Carcinogenicity of 7V-Nitrosoamines We will discuss the carcinogenic properties of nitrosoamines in spite of the fact that it seems to be a problem particularly related to 7V-nitroso derivatives of secondary amines. In 1956, Magee and Barnes found that rats fed with 7V-nitrosodimethylamine developed hepatic tumors. Nitrosoamines cause alkylation of DNA, as suggested first by Druckrey et al. (1967) and Druckrey (1973). They postulated the pathway shown in (4-10), originally for 7V-nitrosodimethylamine, but likely to be valid for all dialkyl- and cycloalkylamines with at least one H-atom bonded to one of the C(a)atoms. The nitrosoamine is metabolized by a cytochrome P450-dependent, so-called mixed-function oxidase. This enzyme catalyzes the hydroxylation of the C(a)-atom * This German word is also used in English, as well as "anglo-americanized" expressions, like "umpoled synthons", although they look and sound unpleasant.

128

4 Kinetics and Mechanism of Aliphatic Diazotization R

.

\_N* R'CH/

/O

R

enzymatic

»

hydrOXylati n

°

X0

\_N* R'C/ OH

R+ -*

RN2+ •«

(4-10)

R— N2-OH + R'CHO

to form a-(hydroxyalkyl)-A^-nitrosoalkylamine and its dealkylation to alkyldiazenol and an aldehyde (formaldehyde in the case of N-nitrosodimethylamine). The alkanediazonium ion will rapidly form the alkyl cation, which is a strong alkylating reagent. The importance of the primary a-hydroxylation was demonstrated by Lijinsky (1982), who showed that 7V-nitroso-2,6-dimethylpiperidine is not carcinogenic, in contrast to 7V-nitrosopiperidine. On the basis of mechanism (4-10), it is likely that nitrosation products of primary amines are also carcinogenic. This is, however, not easy to observe, since nitrosoamines of primary amines very rapidly decompose solvolytically, whereas 7V-nitroso derivatives of secondary amines may accumulate and degrade over a longer period. Indeed, alkylation products of DNA in vitro have been found in the presence of 7Vnitroso-alkyl-ureas (summary: Wiessler, 1986). With Af-nitroso-butylurea, even rearranged butyl-1- and butyl-2- guanine and thymine adducts were found, i. e., products which are typical for the well-known rearrangement of the 1-butyl into the 2-butyl cation. Alkylation under physiological conditions can occur at the ring N-atoms of the DNA bases adenine, guanine, cytosine, and thymine, and also at the O-atoms of hydroxy or carbonyl groups as well as the phosphate groups. The alkylation of the carbonyl group of guanine (so-called O6-alkylation), forming a lactim ether (Antrup and Stoner, 1982) (4-11), is a more sensitive cause of carcinogenicity than TV1 -alkylation.

The differentiation between O- and 7V-alkylation is less pronounced in ethylation than in methylation. The latter occurs preferentially at N centers (Singer, 1975, 1976). Theoretical comparisons of stabilities and dediazoniation reactivities were carried out by Sapse et al. (1988) and, at a more advanced level, by Glaser et al. (1991). These authors found that the activation energy of dediazoniation of the methanediazonium ion is greater than that of the ethanediazonium ion by 128 kJ mol"1. This explains the lower selectivity of the alkylations by ethyl cations.

4.2 Carcinogenicity of N-Nitrosoamines

129

In contrast to 7V-nitrosoamines, TV-nitrosoamides, 7V-nitrosoalkylureas and related compounds are able to alkylate DNA in vitro (Loveless, 1969). They usually cause tumors at the site of administration, indicating that their nonenzymatic decomposition products are again alkyl cations. Nitrosoamides are indeed unstable in aqueous solution. Preussmann and Stewart (1984) investigated over 300 7V-nitroso compounds for carcinogenic potential. Of the 7V-nitrosoamines, 86% were found to be positive for carcinogenicity. For the TV-nitrosoamides, the corresponding figure is 91%. The acute toxicity LD50 of 7V-nitrosodialkylamines is in the range of 18 mg kg"1 (7V-nitrosocyclohexylamine). Alkylureas have LD50 between 100 and 300 mg kg'1 (Druckrey, 1973)*. It is not easy to draw conclusions on the susceptibility of man to 7V-nitroso compounds from studies with animals, as different animals often given quite different tumor responses. For example, in rats the most common site of tumor induction is the esophagus, but in the Syrian golden hamster the esophagus never responds. The pancreatic duct of the hamster, however, is a common target of 7V-nitrosoamines containing a /?-hydroxygenated propyl group, but pancreas duct tumors have never been observed in rats (Lijinski, 1987). N-Nitrosoamines are subject to various acid-base reactions (see Zollinger, 1994, Chap. 5). Obviously, products of such equilibria may be a cause of the carcinogenicity of Af-nitrosoamines. Among the protonated derivatives are O- and 7Vdiazenium ions of secondary 7V-nitrosoamines (4.7 and 4.8, respectively). They were extensively discussed (see, for example, Ohannesian and Keefer, 1988, for Odiazenium ions; Keefer et al., 1988, for TV-diazenium ions). With respect to primary 7V-nitrosoamines, their deprotonation products, the diazenolates (R —N2 —O~), have also been explored (see, for example, Jarman and Manson, 1986; Carmella and Hecht, 1987). Ukawa and coworkers observed that some (Z)-diazenolates are less mutagenic than the corresponding (EHsomers in bacteria (Ukawa et al., 1988) and in mammalian cells (Ukawa and Mochizuki, 1991). Conclusions on correlations between these differences of the biological activities and the purely chemical reactivities of (Z> and (£>diazenolates are premature, however (see remarks by Ho and Fishbein, 1994). In recent years, the compound Af-methyl-AT'-nitro-TV-nitrosoguanidine (4.9, MNNG) has been intensively investigated because it is a powerful direct-acting carcinogen. It is also used as a diazomethane generator that is activated on treatment R

\+

,N=N

^ 4.7

/ OH

\+

// .0

R'— N— N 4.8

* LD50 = 50% lethal dose. It should be emphasized (even in a book for organic chemists) that the LD50 test is now outdated because of the large number of mammals necessary to carry out such tests (see Zbinden, 1981). The European Community issued a statement (Anonymous, 1990) of its intention to replace the LD50 test by the so-called Fixed Dose Procedure.

130

4 Kinetics and Mechanism of Aliphatic Diazotization

with aqueous base (Black, 1983). The anion 4.10 has been confirmed by an X-ray analysis (Rice et al., 1994). The solvolytic decomposition of MNNG leads to methyldiazenolate and the anion of nitrocyanamide, but not directly from the anion 4.10 of MNNG, as postulated by Lawley and Thatcher (1970), but via the mono- and the dianion (4.11), as demonstrated by Fishbein's group (Galtress et al., 1992) in a careful kinetic study in the pH range 6-13 (4-12). Fishbein's result explains also the extraordinary stability of the compound with a methylamino group (A^AP'-dimethyl-A^-nitro-Af-nitrosoguanidine (DMNNG).

(4-12)

Chemoprotection against the alkylating activity of MNNG can be obtained by a glutathione-S-transferase *, which has been isolated by Jensen and Mackay (1990). It is likely that this transferase affords chemoprotection by selectively catalyzing the denitrosation of MNNG by glutathione. Therefore, Santala and Fishbein (1992) investigated the alkanethiolate-stimulated decomposition of MNNG in aqueous solution. Two competitive reactions were detected and kinetically investigated, namely the deamination to methyldiazenolate and to the thiol [RS-(Af-nitroformamidino)] adduct (4.13) and reaction to methyl-nitroguanidine (4.14), which is a denitrosation product. The yield ratio is strongly dependent on the basicity of the thiolate anion. The yield of methyl-nitroguanidine increases with decreasing basicity (90 % with pentafluoropropanethiolate). Kinetic studies demonstrate that the deamination is consistent with an addition intermediate (4.12) of the thiolate ion. For the denitrosation, the present data do not allow a differentiation among several possible mechanisms. The thiolate deamination mechanism of MNNG is analogous to that investigated by the same group (Wichems et al., 1992) where deamination was catalyzed by cyclic amines. How are the nitrosoamines formed in a living organism? Apart from the possibility that nitrogen oxides are taken up from the environment, endogenic ways of forming enzymatic nitrosating agents are likely to be in operation, as work of en* Glutathione is the tripeptide built up from glutaminic acid, cysteine, and glycine.

4.2 Carcinogenicity of N-Nitrosoamines

131

NH2

\c

NH2

C-NNCV 2 | _ NH2 I

/

ON

'

RS

^

^ ^NNO* 4.13 +

^CH3 4.12

CH3-N2-0-

(4-13) NH2 CH3 49

'

^

| ^

RSNO +

HN^ CH3

4.14

zymologists shows. Stuehr and Marietta's group demonstrated, for example, that immunostimulated macrophages can oxidize the N-atom in arginine to form a nitrosating agent that converts secondary amines to their N-nitroso derivatives before formation of free nitrite and nitrate (lyengar et al., 1987). Such a reaction was mimicked in vitro by Stershic et al. (1988) with the help of a polypyridylammineosmium(ii) complex and diethylamine in a phosphate buffer (pH 6.8) and by a potential of 0.65 V (vs. calomel). The ammine complex was indeed transformed into an 7V-nitroso- diethylamine complex. For these reasons, structure-reactivity relationships in carcinogenesis by N-nitroso compounds are difficult to generalize (see Lijinski, 1987, 1992; Dai and Zhong, 1987). A short book on the toxicology and microbiology of nitrosoamines was edited by Hill (1988). Another book on chemical carcinogens, edited by Searle (1984), contains three chapters on nitrosoamines. Some nitrosoamines have other biological effects than carcinogenic action. N-(2Chloroethyl)-7V'-cyclohexyl-Ar-nitrosourea (4.15) has a cytostatic effect (Ferguson, 1975) and another 7V-nitrosourea derivative, streptozotocin (4.16), is an antibiotic (Herr et al., 1967). Various types of triazenes [RR'N-N 2 -R", R,R',R" = alkyl, aryl, H, etc.) are interesting with respect to carcinogenicity. We discuss aliphatic triazenes briefly in this section although they are not directly related to 7V-nitrosoamines *. 1,3-Dialkyl- and 1,3,3-trialkyltriazenes can be obtained from alkyl azides (Sieh et al., 1980a; Smith and Michejda, 1983). Hydrolysis of triazenes leads to amines (RR'NH2) and metastable alkanediazonium ions (R"N2+; see Smith et al., 1984, 1986, 1989), which decompose in the ways discussed in Chapter 7. 1,3-Dialkyltriazenes (KroegerKoepke et al., 1991) and 1,3,3-trialkyltriazenes (Sieh et al., 1980b) exhibit a high level of mutagenicity by alkylation of the Opposition of guanine in DNA of Salmonella typhimurium. The mutagenic activity follows the order methyl > ethyl > butyl.

* For a review of the carcinogenicity and mutagenic properties of l-aryl-3-mono- and -dialkyltriazenes, see Zollinger, 1994, Sect. 13.4.

132

/

4 Kinetics and Mechanism of Aliphatic Diazotization

V-NH—C —N—CH2CH2CI

NO 4.15

4.16

1-Alkyl-triazolines (4.17) were investigated more recently by the same group (Smith et al., 1993). These compounds may be considered as cyclized (Z)-triazenes. It was deduced from very similar dose-response curves for 1-methyltriazoline and 1-methylaziridine and from comparison of the activities of alkyltriazolines, alkyltriazenes, and alkylaziridines that the ultimate mutagenic intermediate is the aziridinium ion 4.18 and not the diazonium ion (4-14).

(4-14)

4.3 Mechanisms of Diazoalkane Syntheses In this section we will review mechanistic investigations on some synthetic routes to diazoalkanes. As discussed in Chapter 2, diazotization of primary aliphatic amines generally does not lead to diazoalkanes, because the intermediate alkanediazonium ion loses the diazonio group faster than a proton of the C(a)-atom. Diazoalkane formation is dominant if the deprotonation rate is increased by acidifying substituents in the a-position (see Sect. 2.3). Curtius' synthesis of ethyl diazoacetate (1883) is the classical example. Hart and Brewbaker (1969) showed clearly that acidifying substituents favor diazoalkane formation over dediazoniation; electron-donating substituents exert the opposite effect. One might expect that diazotization of aliphatic amines under alkaline conditions or in the presence of strong proton acceptors used for general base catalysis might also yield diazoalkanes. This alternative route, however, has not been successful so far, as shown by the experiments of Maltz et al. (1971), who nitrosated amines with disodium pentacyanonitrosyl ferrate (Fe[CN]5NO2~Naih) at pH up to 12.7 (see Sect. 2.3).

4.3 Mechanisms of Diazoalkane Syntheses

133

Under alkaline conditions, on the other hand, diazenols and diazenolates may also be involved, in particular, as well known for diazoalkane formation via the Nalkyl-7V-nitrosoamides, -urethanes and related 7V-nitroso compounds (see Sect. 2.4). The intermediacy of diazenolates already has been observed qualitatively by Hantzsch and Lehmann (1902). The investigation of hydrolytic partitioning of alkyldiazenolates into diazoalkanes and dediazoniation products (4-15) was started by Moss (1966) and Kirmse and Wachterhauser (1967). With R = methyl, benzyl, or allyl in (4-15), the diazoalkane is the main product; with R = alkyl a rather even partition between the two pathways was found; secondary alkyldiazenolates gave almost exlusively dediazoniation products. It is interesting to note that most of the investigations were carried out in the years in which primary interest on these reactions concentrated on carbocation chemistry and less on diazoalkane formation (see, e.g., review by Moss, 1974). We refer also to the corresponding discussion (Sects. 7.2-7.5). dediazoniatlon products

R—N

(4-15)

More recently, Fishbein and coworkers investigated in detail the kinetics of the decay of six alkyldiazenolates, namely (^-methyldiazenolate (Hovinen and Fishbein, 1992; Hovinen et al., 1992), (£>butyldiazenolate, (£>methoxyethyldiazenolate, (£>cyanoethyldiazenolate, (Z)- and (£T)-2,2,2-trifluoroethyldiazenolate (Ho and Fishbein, 1994) in water (in part with 4% 2-propanol by volume) at 25 °C and ionic strength of 1 M NaClO4. We shall discuss the majority of Fishbein's results in Section 7.2, because intermediate or final formation of the corresponding diazoalkanes was not detectable, except for (Z)-2,2,2-trifluoroethyldiazenolate. This compound is more reactive than the (£>isomer by a factor of 2600. This result presents not only the first quantitative analysis of the difference in reactivity between identically substituted (Z)- and (^-alkyldiazenolates*, but also the first observation of 2,2,2-trifluorodiazoethane in spectra taken immediately after mixing in the stoppedflow spectrophotometer. The final product, however, is 2,2,2-trifluoroethanol in fairly high yield (86%), as in the reaction of the (£>isomer (94%). In addition, dediazoniation of the (Z)-isomer exhibits general acid catalysis. The mechanism is likely to be a concerted assistance of the acid to diazonium ion formation from the diazenol and a rapid side equilibrium to the diazoalkane (4-16). This mechanism is supported by H/D-exchange results in D2O.

* A ratio of kz/kE = 105 was determined for the dediazoniation of methyl 4-nitrophenyldiazenolate by Broxton and Stray (1982).

134

4 Kinetics and Mechanism of Aliphatic Diazotization CF3CH2-OH

(4-16)

CF3CH2— N2+ + H2O + A

As already mentioned, the most important type of diazoalkane syntheses starts from 7V-nitroso-Af-acylalkylamines and related compounds, since von Pechmann (1894) developed the first synthesis for diazomethane. Generally, mechanism 4-17 is proposed for the formation of the alkyldiazenolate and the release of the carboxylate group. The diazenolate with (Z)-configuration is assumed to be the product, as established by X-ray analyses (Muller et al., 1960 b, 1963) and NMR (Suhr, 1963; White et al., 1972). (Z)-Diazenolates were also obtained from 7V-nitroso-7V-alkylurethanes. (£")-Diazenolates react in a similar way, also forming diazoalkanes and dediazoniation products (Thiele, 1908; White et al., 1972). The relatively high yields of diazoalkanes obtained with Af-nitroso reagents are difficult to understand considering the much lower yields obtained from isolated (Z)- or (£)-diazenolates *. On the basis of recent results of Fishbein's group (see above), a comparative study of the yields of diazoalkane from an 7V-nitroso-7V-acylalkylamine and by hydrolysis of the corresponding (Z)- and CE^-diazenolates under strictly identical reaction conditions is desirable. O >

N

0

_pc2H5 -

X

OC2H5

R

*

X

II /N R

OR'

+

XC=0

(4-17)

R'O

The diazo transfer reactions, discussed in the synthesis Sections 2.6-2.8 clearly indicate that arylsulfonyl azides and other compounds with the azido group act as electrophilic reagents, that add to nucleophiles, e.g., to C-anions of so-called active methylene compounds. This result is qualitatively easy to comprehend, since the N(/?) and N(y)-atoms of the azides are electronically similar to the diazonio group, as shown in the mesomeric structures 4.20b-4.20c. ArSO2— N—N=N 4.20a

^

*~ ArSO 2 —N—N=N 4.20b

*

>-

ArSO2—N—N=N 4.20c

* In that context, Huisgen's result (1951 b) stating that cyclic aromatic 7V-nitrosoacylamides (4-18) are rearranged into cyclic diazo esters only if the ring size is suitable for the formation of the (£>compound 4.19 (n = 3 or 4), should be taken into consideration (review: see Zollinger, 1994, p. 138f).

4.3 Mechanisms of Diazoalkane Syntheses

C= O

135

(4-18)

4.19

Indeed, Regitz has found (1964 b, 1965 b) a 1:1 adduct of 4-toluenesulfonyl azide with the potassium salt of l-(2/,4',6'-trimethylphenyl)-2-phenyl-ethan-l-one to which he ascribed the structure 4.21. The latter can be isolated and reacts to give the 2-diazo derivative 4.22 (4-19). Ar ^C—CH—C6H5 K+ + O

^C~C^ _ O N 2 —N—Ts

Ts —N3

K+

N

N2

(4-19)

Ar = H3C

4-21

// Cf

CH3

+ Ts—NH K+

4.22

We claim, however, that this reaction is likely to be more complex *. The isolated intermediate salt may be the prototropic isomer 4.23 formed intermolecularly from 4.21, which is the primary steady-state intermediate. Compound 4.23 is energetically more favorable because in 4.23 — in contrast to 4.21 — conjugation (7c-orbital overlap) between the arylcarbonyl part and the 4-toluenesulfonyl azide part is not interrupted by an sp3 C-atom. Intermediate 4.21 may, however, also react directly to give the diazoketone 4.22 via a cyclic transition state 4.24 that contains, however, a less favorable (Z)-azo group. The prototropy 4.21 <=* 4.23 was included at an early date for the mechanism of the diazo transfer from 4-toluenesulfonyl azide to the cyclopentadienyl anion by Roberts (see review Roberts, 1990, p. 217) and by Huisgen (1990). A transition state similar to 4.24 was mentioned by Balli et al. (1974) for the diazo transfer of azidinium salts to pyrazolin-5-one and 5-aminopyrazole compounds (see below). * See also the remark by March (1992, p. 594).

136

4 Kinetics and Mechanism of Aliphatic Diazotization

Today, it would be easy to assign either structure 4.21 or 4.23 to the isolated intermediate on the basis of NMR spectroscopy. Evidence for the hypothetical cyclic transition state is more difficult to find. Activation entropies of the second step of (4-19) may offer an answer based on comparative data of compounds where such a transition state is impossible. Ar,

Ar A

C6H5

/C—Cx 7

O

4.23

K+

\

-

6-1 -

5'I—Ts

N2—NH—Ts

4.24

When 1,2-diphenyl-l-ethanone (4-19, Ar = C6H5) was used by Regitz (1964 b, 1965 b) a rather unstable intermediate and another end product were found in addition to the diazoketone 4.22 (Ar = C6H5). In our opinion there is not enough mechanistic information available for an interpretation, considering also the experience with 15NY-labeled 4-toluenesulfonyl azide in the reaction with cyclopentadienyl anion. For these reactions Roberts and coworkers found, besides the expected diazocyclopentadiene with 15N in the a-position, some 15Np-labeled product (Duthaler et al., 1978). Mechanistically interesting methods were developed by Balli's group for the investigations of cyclic azidinium salts as diazo transfer reagents (see Schemes 2-61 2-63 in Sect. 2.6). Balli et al. (1974 b) measured the rates of reaction of twelve azidinium tetrafluoroborates of the general structure 4.25 with l-(4'-sulfophenyl)-3-methylpyrazolin-5-one (4.26) and l-(3'-sulfophenyl)-3-methyl-5-aminopyrazole (4.27) in aqueous buffer solutions (4.26: pH 1.69-4.60, 25 °C, ionic strength 0.05 M" 1 ; 4.27: 40 °C, ionic strength 0.10 M" 1 , pH not given). Among these twelve azidinium salts were 2-azido-3-ethylbenzothiazolium tetrafluoroborate, which is the azidinium salt most frequently used for diazo transfer reactions (see Sect. 2.6, 2.144), l-ethyl-2-azido-pyridinium tetrafluoroborate (4.28), which has the lowest reactivity of the series, 2-ethyl-3-azido-benz[rf]isothiazolium tetrafluoroborate (4.29; highest reactivity) and various azido-indazolium, -chinolinium, -thiazolium, -benzo[rf]isoxazolium, -benzoxazolium, -benzo[c,d]indolium, -naphtho[2,\-d\thiazolium, and -benzoselenazolium tetrafluoroborates *.

4.26

M

3^

The sequence of these salts indicates increasing diazotransfer reactivity.

4.27

4.3 Mechanisms of Diazoalkane Syntheses

4.28

137

4.29

As shown in Scheme 2-61, the diazo transfer is a dihydro-de-diazoniation of the azidinium ion leading to the 2-amino-3-ethyl-benzothiazolium ion (4.30). This compound was characterized by Balli et al. (1974 a) as an N-acid; deprotonation gives 2-imino-3-ethyl-benzothiazol (4.31). (4-20)

Balli et al. (1974 b) showed that there is a free-energy relationship between the acidity constants Ka and the rate constants of the two series of diazo transfer reactions of the twelve azidinium salts mentioned above with the two diazo acceptors 4.26 and 4.27 following Equation 4-21. In analogy to Swain and Scott's nucleophilicity equation (1953), Balli's group developed the linear free-energy relation 4-21 for the electrophilicity of azidinium salts. If aHet = 0 is correlated with the slowestreacting azidinium ion (4.28) and p = 1 with the pKa values of the acid-base systems of type 4-20, good linear relationships are obtained. This result is consistent with a rate-determining addition of the azidinium ions to the two substrates 4.26 and 4.27. log(/c//co)=p<7Het

It is also interesting to note that the rates for the more reactive azidinium ions (&« 107 M"1 s"1) are higher than the rates of azo coupling reactions of the same substrate (4.26) with arenediazonium ions within a factor of 1.1-2.1 (Dobas et al., 1969), and that the aminopyrazole 4.27 reacts slower with azidinium ions than the pyrazolone 4.26 by a factor of 1500. This difference is comparable to that in azo coupling reactions of 2-naphthylamine-6-sulfonate anion and 2-naphtholate-6-sulfonate dianion (rate ratio 1:330, Zollinger, 1953). Several readers of this section would be disappointed that not more mechanistic results that can certainly be found in the literature are discussed here. There is no doubt that there are investigations of good quality, but in most cases it is my feeling that they are useful and interesting only within the limits of the specific reaction or structure involved, but not for a broader scientific context. This is the reason for the brief character of this section. It demonstrates a very significant difference in the mechanisms of diazotization of aromatic and aliphatic primary amines!

138

4 Kinetics and Mechanism of Aliphatic Diazotization

4.4 Acid-Base Equilibria of Aliphatic Diazo Compounds Huisgen's classical review (1955) on the reactivity of aliphatic diazo compounds starts with the statement "Die Diazoalkane zeigen in ihrer Reaktivitat eine erstaunliche Vielseitigkeit, die hinter der der aromatischen Diazo-Verbindungen nicht zuriicksteht" (The reactivity of diazoalkanes shows an amazing versatility that is not inferior to that of aromatic diazo compounds). Huisgen's aim at that time was to demonstrate that work on diazoalkanes should not be restricted to "formal analogies" (to aromatic diazo compounds) or to incidental discoveries. Indeed, his synopsis of experimental results obtained during the preceding seven decades demonstrates that a systematic classification of the known facts is possible and allows extentions — extensions to which Huisgen made interesting contributions in the immediately preceding half decade. The vast majority of diazoalkane reactions are based on the ambident nucleophilic character of diazoalkanes, as shown by the mesomeric structures of diazomethane 4.32 a and 4.32 b. Br0nsted and Lewis acids can be added at the C- and the N(/?)atoms. The reaction with Br0nsted acids is particularly important. Alkanediazonium ions are obtained by proton addition at the C-atom giving rise to dediazoniation and various reactions of carbocations (see Chapt. 7). In addition to Br0nsted acids, Lewis acids of various types, e. g. , carbonyl compounds, 1,3-dienes, and many others react at the nucleophilic C-atom of diazoalkanes, as already depicted systematically by Huisgen in 1955*. In the context of diazo chemistry the reaction with arenediazonium salts, discovered by Huisgen and Koch (1954, 1955), is particularly interesting. 4-Nitrobenzenediazonium chloride undergoes an azo coupling reaction at the C(a)-atom of ethyl diazoacetate at 0°C in methanol with dediazoniation of diazoacetate. With diazomethane the primary azo coupling and dediazoniation are followed by a rearrangement, the mechanism of which was elucidated by 15N labeling in a joint investigation of Clusius and Huisgen (Clusius et al., 1954). We have previously discussed this in detail (Zollinger, 1994, p. 340).

4.32b

The mesomeric structures with electron sextets at the N(/?)- (4.32 c and 4.32 d) and the C-atom (4.32 e) are the basis for understanding that diazoalkanes also have the properties of Lewis acids, and may react at these centers (see Sect. 9.2). Dediazoniation of diazoalkanes also takes place, however, without primary addition of a Br0nsted or Lewis acid at the C-atom. Carbenes are obtained thermally, photolytically, and by transition-metal catalysis (Chapt. 8). For up-dated reviews see Regitz and Maas, 1986, Chapt. 14, and this book, Sections 8.6 and 9.1.

4.4 Acid-Base Equilibria of Aliphatic Diazo Compounds

139

Reactions with radicals were hardly known when Huisgen published his review in 1955 and, even today, homolytic processes involving diazoalkanes are not numerous. One group of reactions that is very important nowadays was not mentioned in Huisgen's review - simply, because he did not realize in 1955, that five years later he would discover that a few reactions known since the late 19th century were the nucleus of the class of 1,3-dipolar cycloadditions! Diazoalkanes were the first and are probably the most widely used representative of some twenty 1,3-dipole reagents known today (Sects. 6.2-6.5)*. As indicated in the title of this section we concentrate here on the acid and base equilibria of aliphatic diazo compounds, emphasizing their quantitative aspects. The protonation equilibria of diazoalkanes in solution are of primary importance. Investigation of them, however, is extremely difficult because the diazoalkanes undergo rapid dediazoniation in acid solution. To a certain degree, the paucity of equilibrium measurements is compensated by a wealth of relevant kinetic data, which allow at least some semiquantitative conclusions to be drawn. As early as 1907, Fraenkel measured the rate of decomposition of ethyl diazoacetate in 10 ~3 M aqueous nitric acid and found that it was first-order in diazoacetate and nitric acid. As early as 1905 Bredig and Fraenkel used that decomposition rate as a dynamic method for the determination of hydroxonium ions — a welcome device long before commercially available electronic equipment and glass electrodes were used for pH determination! ** Albery and Bell showed in a classical paper (1961) that the protonation rates of ethyl diazoacetate correlate with Hammett's acidity function HQ up to the fastest rates measured. Experiments with acids in aprotic solvents indicated, however, general acid catalysis (Br0nsted, 1928), but also showed second-order kinetics with respect to the acid. In the 1920's to 1930's and again in the period 1950-1970 almost the whole spectrum of kinetic and related methods for the investigation of mechanisms was applied to dediazoniations of aliphatic diazo compounds (see summaries by Hegarty, 1978, p. 571, and McGarrity, 1978, p. 182). The following types of mechanisms were found: 1) Pre-equilibrium protonation (Scheme 4-22) was found to be typical for diazomethane, for diazoacetates (R = C2H5O2C -; R' = H), a-diazo ketones (R = R" - CO, R' = H) in aqueous or partly aqueous systems. These reactions are characterized by specific, not general, acid catalysis, by faster reaction in D2O than in H2O, because D3O+ is a stronger acid than H3O + , and by deuterium exchange (R7 = H replaced by D). Results have been summarized by More O'Ferrall (1967). The mechanism of the dediazoniation and subsequent product-forming steps (reaction with nucleophiles Nu, rearrangements, alkene formation) are not within the scope of this section (see, however, Sects. 7.3 and 7.4).

* Scheme 6-6 in Section 6.2 demonstrates that the bifunctional character of 1,3-dipoles is easily explainable on the basis of the four mesomeric structures 4.32a-c and e. ** At a much later date, Shorter and his coworkers (Aslam et al., 1981) used the rate of reaction of diazodiphenylmethane with benzoic acid for a comprehensive correlation analysis for 23 alcohols and 44 aprotic solvents.

140

4 Kinetics and Mechanism of Aliphatic Diazotization

products

(4-22)

2) Rate-determining proton transfer takes place with mono- and diaryldiazomethanes (R = Ar, R' = H and Ar, respectively) and with secondary diazo ketones (R = R"-CO, R' = CH3). Proton transfer (ki in 4-22) is not necessarily slower than in the reactions discussed under 1), but &2 is, relative to Ar_ l 5 faster. General acid catalysis is observed (in the case of diphenyldiazomethane with a Br0nsted coefficient a « 0.5, Diderich and Dahn, 1970). Primary kinetic isotope effects with monoaryldiazomethanes (R' = D in 4-22) show k^/kD = 3.5-3.6 with acetic and benzoic acid being general catalysts (More O'Ferrall et al., 1964, and earlier papers mentioned there). The reaction is, in contrast to reactions of type a), faster in H2O than in D2O (Dahn and Diderich, 1971). The participation of the second step in the rate-limiting part of the reaction is documented by a rate increase with stronger nucleophiles (Nu = Cl~ < Br~ < I~ < NCS~, Swain-Scott relationship, Swain and Scott, 1953). 3) In aprotic solvents. The mechanism of protonation is basically the same as that discussed above. The second order term observed by Br0nsted (1928, see above) is due to an equilibrium of the acid catalyst forming dimeric aggregates. Therefore, fastest rates are measured in dipolar aprotic solvents, e.g., dimethyl sulfoxide (Blues et al., 1974). All these kinetic measurements verify a prediction made by Staudinger and Gaule at a very early date (1916), namely, that with acetic acid or trichloroacetic acid in inert solvents the reactivity of substituted diazoalkanes and a-diazo-carbonyl and a,a'-dicarbonyl diazo compounds increases as the protonation equilibrium is shifted towards the corresponding alkanediazonium ion. This prediction includes the compounds listed in sequence 4-23:

HsCs, H2C=N2

-

H3C—CH=N2

>

C=N2 XC=N H3C

HsCe^ > > H6C6

(4-23) W

^C=Ng ROOC^ H5C6-q; > ,C=N2 = \\ ROOC O

o The reactivity sequence stated by Staudinger and Gaule was the very early qualitative precursor for the quantitative determination of the acid -base equilibrium constant of diazomethane by McGarrity and Smyth (1980). The major difficulty of

4.4 Acid- Base Equilibria of Aliphatic Diazo Compounds

141

such work on the thermodynamic aspect of diazoalkane protonation is, of course, the rapid and practically irreversible dediazoniation of the system (4-22). McGarrity and Smyth, however, were able to measure the rate constant of the nucleophilic attack of water and hydroxide ion on the methanediazonium ion (k-\ and A^, respectively) in THF- water (60: 40 v/v) at 25 °C, using a continuous flow system for kinetics and pH measurement (pH 4.0-5.5). H/D exchange studies showed that the deprotonation of methanediazonium ion (£_i) is slower than the addition of water as nucleophile in the dediazoniation (k2). Hydroxide ion, however, is slower as nucleophile than as proton acceptor. The measured rates allow calculation of a pKa value of 10 for the methanediazonium ion in this system. This acidity is comparable to that of nitroalkanes (p#a = 10.2, TUrnbull and Maron, 1943) and acetylacetone (p#a = 9, Pearson and Dillon, 1953). It is, however, quite different from another monosubstituted methane, i.e., acetonitrile (CH3 — C^N, pKa = 25-31, Hibbert, 1983, p. 700 and 733; for a review of carbon acids in general see Jones, 1973). The H/D exchange of methanediazonium ion, generated from four precursors of diazomethane (A^-acetoxymethyl-7V-nitrosomethylamine, 7V-methyl-7V-nitrosoethyl carbamate, 1-methyl-l-nitrosourea, and 1,3,3-trimethyltriazene), was investigated by Smith et al. (1985) in phosphate buffers/D2O at pH 7.4 (20 °C). The results are consistent with the Scheme (4-24). CH2N2 CH3N2+

* ^

CHDN2 CH2DN2+^

^ ^

^

CD2N2 ^ ^

CHD2N2+>^

^

^ CD3N2+ ^ (4-24)

I D20

CH3OD

I D2O

CH2DOD

I D20

CHD2OD

D2O

CD3OD

We have already mentioned in Section 2.1 that the generation of methanediazonium ion in an ion cyclotron (Foster and Beauchamps, 1972; Foster et al., 1974) demonstrated that this ion has a much greater stability against dediazoniation in the gas phase than in solution. These authors also found that the generation of methanediazonium ion is very suitable for subsequent proton transfer reactions leading to diazomethane with ammonia, azomethane, and methylamine as proton acceptors. These experiments allowed the conclusion that the proton affinity of diazomethane (gas-phase basicity, see below) is higher than that of ammonia, but lower than that of azomethane and methylamine. This sequence is therefore quite different from basicities in solution! Gas-phase acidity and basicity became a diversified and extensively investigated field of physical chemistry, not least, as an experimental counterpart to theoretical work that is, in almost all investigations, conducted without taking account of solvent interaction. We will not discuss the general literature on the theory and techniques of gasphase acidity and basicity here (see, e.g., Bowers, 1979; Gal and Maria, 1990). They are defined as the Gibbs free energies (AG°acid and AG°base) of the ionization for the gas-phase acidity of an acid into the corresponding base and a proton, and analogously for the basicity (see Gal and Maria, 1990, p. 169 ff). The ther-

142

4 Kinetics and Mechanism of Aliphatic Diazotization

modynamics and kinetics of that dissociation are, of course, influenced by the basicity of the corresponding proton acceptor. To eliminate this influence, in the socalled bracketing technique, the acid is allowed to react with a series of proton acceptors, A~, of known basicity, and the occurrence or nonoccurrence of proton transfer is monitored as indicated above in the classical, semiquantitative work on the basicity investigation of diazomethane by Beauchamp's group: In this way Foster et al. (1974) estimated the acidity of the methanediazonium ion, i. e., the basicity of diazomethane, to be ca. 867 kJ mol"1 (first step in 4-25). A more accurate determination was made by McMahon et al. (1988) (886 kJ mol"1). CH3N2+

«

>

CH2=N2

<

»

CH=N2

(4-25)

The second step of (4-25) refers to the acidity of diazomethane, i.e., to its deprotonation to the diazomethyl anion. Diazoalkyl anions were obtained in solution by reaction of a carbanion with nitrous oxide (4-26) (Bierbaum et al., 1977). R—CH2 + N2O —>—*»

RC = N2 + H2O

(4-26)

It would appear today, however, that the acid-base equilibrium of diazomethane with its anion is better known in the gas-phase than in solution! The same group (DePuy et al., 1989) investigated reactions of the diazomethyl anion with CS2, COS, CO2, SO2, and with a series of a,/?-unsaturated aldehydes and ketones — all in the gas phase using a flowing afterglow apparatus (DePuy and Bierbaum, 1981) and selected ion flow tube techniques (Van Doren et al., 1987). For the acidity of diazomethane, DePuy et al. (1989) showed that it is AG°acid = 1526 ± 12 kJ mol"1, because they found that diazomethane reacts rapidly by proton transfer to the three bases A~ (NH2~, HO~, and HO2~) (AG°acid(A~) = 1655 ± 3, 1605 ± 2, and 1542 ± 3 kJ mol"1, respectively), but reacts slowly and incompletely with F~ (1529 ±2 kJ mol"1). With acetone enolate ion (1509 ± 8 kJ mol"1), only traces of diazomethyl anion were found; therefore, the acidity of diazomethane appears to lie between that of H2O2 and acetone. In analogous fashion, Kroeker and Kass (1990) found that diazomethane is more acidic than diazirine (AG°acid = 1647 ± 13 kJ mol"1), but less acidic than cyanamide (H2NCN, AG°acid = 1463 ± 13 kJ mol"1). This comparison is interesting, because these two compounds are isomers of diazomethane (see Sect. 5.4). Another interesting equilibrium study of methanediazonium ion was realized by Kebarle's group (McMahon, 1988). Although it does not need to be considered within the scope of this section, we will review it briefly here. These authors measured methyl cation transfer equilibria for the dilute gas-phase reaction 4-27 with B'CH3+ + B <

*

B' + BCH3+

(4-27)

4.4 Acid-Base Equilibria of Aliphatic Diazo Compounds

143

a pulsed high-pressure mass spectrometer and an ion cyclotron resonance mass spectrometer and determined a scale of relative methyl cation affinities of 24 bases B, MCA(B). The experiments and, therefore, the scale were calibrated to the methyl cation affinity of N2, which was calculated from the known heats of formation of methanediazonium ion (A//?-890 kJ mor1) and methyl ion (A//?= 1095 kJ mol"1). Thus, one obtains for the process 4-28 MCA(N2) = 1095-890 = 203 kJ mol-1). CH3N2+ «

N2 + CH3+

(4-28)

Experimentally, it is interesting that the primary reagent for the production of the methyl cation in 4-28 and in systems with other bases was dimethylfluoronium ion (CH3&CH3). This ion was formed from CH3F in the presence of dinitrogen and reacted with the latter following the equilibrium 4-29. Disturbing side reactions could be eliminated only in a relatively small range of initial concentrations (N2 667 Pa; CH3F 0.667 Pa). With lower concentrations of CH3F a complex mixture of primary products, e.g., N^, N 3 + , and N4+ in the first 0.1 msec after the electron pulse (McMahon, 1988, Fig. 1) was observed. CH3FCH3 + N2

<

»

CH3F

+ CH3N2+

(4-29)

Free energies, relative to those of CHsN/, for 23 bases B in Scheme 4-27, including the extremely weakly basic inert gas krypton, covered a range of —9.2 kJ mol"1 for B = Kr to 58 kJ mol"1 for B = CH3Br. Theoretical investigations into the proton affinity of diazoalkanes have been made since the 1970's. Among the older work, the paper of Niemeyer (1976) has some relevance in the context of this section. On the basis of CNDO/2, MINDO/3 and ab initio calculations (the latter at STO-3G and 4-31G levels) Niemeyer concluded that C-protonated diazomethane is more stable than the N(/?)-protonated isomer, and that protonation is exothermic. Glaser and Choy (1991) calculated the energy change of protonation of diazomethane, nitrous oxide and hydrazoic acid at RHF/6-31G* and MP2/6-31G* levels (945, 585, and 792 kJ mol"1, respectively). Consideration of vibrational zero-point energies reduces these values to 907, 560, and 757 kJ mol"1, respectively. The value of diazomethane (907) corresponds reasonably well to Beauchamp's experimental value mentioned earlier (p. 142, 867 kJ mol"1)*. Later Horan and Glaser (1994) were able to get an even better value (883). It is discussed in Section 5.3.

* The basicities of the three compounds mentioned have already been estimated earlier by Jolly's group (Beach et al., 1984) using the so-called equivalent-cores application (diazomethane: 865 kJ mol-1).

5 The Structure of Aliphatic Diazo Compounds

5.1 Aliphatic Diazonium Ions In contrast to arenediazonium salts (see Zollinger, 1994, Sect. 4.2), our knowledge of the structure of alkanediazonium salts is still limited. Alkanediazonium ions have been identified as relatively stable entities only in solution so far. Therefore, no X-ray structures are available. As discussed in Section 2.1, Mohrig and Keegstra (1967) obtained 2,2,2-trifluoroethanediazonium ion by protonation of 2,2,2-trifluorodiazoethane in fluorosulfonic acid at — 78 °C. This diazonium ion and two others identified subsequently by protonation of the corresponding diazoalkanes in super acids by Diderich (1972, l-phenyl-2,2,2-trifluorodiazoethane) and by Mohrig et al. (1974, bis(trifluoromethyl)diazomethane) were characterized by !H and 19F NMR (8 and JHF, see Sect. 2.1). Berner and McGarrity (1979), and McGarrity and Cox (1983) obtained the parent ion, methanediazonium ion, by protonation of diazomethane with fluorosulfuric acid in sulfuryl chlorofluoride (SO2C1F) at -120°C. McGarrity et al. (1980) were, however, unable to identify the ethanediazonium ion under these conditions, only the rearranged product, ethenediazenium ion (CH3 —CH = N^ — H, see Sect. 2.1), was detected. !H and 13C data for some diazonium ions are given in Table 5-1. The *H chemical shift of the methanediazonium ion correlates well with that of methyl groups attached to other strongly electron-withdrawing substituents. Table 5-1. 1H and compounds.

13

C NMR data for alkanediazonium ions, alkenediazenium ions, and related

8 IH

8 13C

Reference a'

4.75s

44.5 q

McGarrity and Cox, 1983

7.22 d 14.lt

76.6 dt

McGarrity and Cox, 1983

3.28s

23.3 t

Albright and Freeman, 1977

2.41 dd 7.52 dq 13.48 dq

—

McGarrity et al., 1980

CF3 — CH2— N2+

6.3 q

-

Mohrig and Keegstra, 1967

CH2=C = CH2

4.55s

74.0 t

Whipple et al., 1959

ow CH2:=N2— H CH2=N2 CH3— CH=N 2 — H

a)

See references for coupling constants.

Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

146

5 The Structure of Aliphatic Diazo Compounds

No counter ion effect is discernible for samples with other anions. The protoncoupled 13C NMR spectrum consists of a quartet (/= 163 Hz), as expected for CH 3 -N 2 + . The multiplicity of the !H NMR spectra of methene- and ethenediazenium ions (see Table 5-1) show the expected coupling for slow exchange. The triplet of doublets in the 13C NMR spectrum of methenediazenium ion is consistent with the assigned structure. The 13C NMR chemical shift of this ion is comparable to that of the terminal C-atoms in allene. The JH chemical shift and the splitting of the 2,2,2-trifluoroethanediazonium ion are consistent with its structure; the shift change relative to the methanediazonium ion is considerable but fairly well understandable. Our knowledge on the electronic structure of alkenediazonium salts was modest for a long time. It was assumed, however, that mesomeric structures involving substituents at the C-atom had to be considered due to the fact that practically all isolated alkenediazonium salts (see Sect. 2.10) have electron-donating substituents (see Sect. 5.3). Recently, however, Glaser's group (Glaser et al., 1992 c; Chen et al, 1993) investigated 2,2-diethoxy- and 2,2-dichloroethene-l-diazonium hexachloroantimonate by IR, *H and 13C COSY NMR spectroscopy, and by X-ray structure determination. Both compounds are characterized by two symmetry-independent cations in the assymmetric unit of the monoclinic unit cell of the crystals. With respect to atomic distances and bond angles, the two cations differ, however, only little. In particular, the C = C bond lengths are significantly longer (137.4 pm and 137.8 pm for the two cations of the diethoxy derivative, 134.4 pm and 135.0 pm for the dichloro compound) than those of typical alkene C = C bonds (129.0 pm, see Allen et al., 1987). MO calculations of geometries and charge localizations are consistent with these experimental results (see Sect. 5.3).

5.2 Diazoalkanes and Related Compounds The question whether the structure of diazomethane and ethyl diazoacetate was linear or cyclic was clarified in favor of the linear structure by Boersch's X-ray diffraction investigation in 1935 (see Sect. 1.1) *. We start this section with the discussion of bond lengths and bond angles of diazomethane on the basis of Boersch's results and those of the microwave investigation of Cox et al. (1958) and Moore and Pimentel (1964b) (Fig. 5-1). The N = N bond is longer than the N = N bond in dinitrogen (109.76 pm, Davis and Ibers, 1970) and in arenediazonium ions (108-111 pm, see Zollinger, 1994, Sect. 4.2), but much shorter than an N=N bond in azoalkanes (149.3 pm) or in azobenzene (143.1 pm)**. The CN bond is much shorter than a C(sp3)-N(sp3) bond (146.9 pm) * Further historical problems of the structure of diazomethane are discussed in Section 5.4 in the context of its isomers. ** Comparative data from Allen et al. (1987) if no reference is given.

5.2 Diazoalkanes and Related Compounds

147

116.5°

127° 132pm

112pm

N(2) v '

107.5 pm

Fig. 5-1. Bond lengths and bond angles in diazomethane (Cox et al., 1958; CH bond length from Moore and Pimentel's IR analysis, 1964 b).

or a C(sp3)-N(sp2) bond (145.8-147.9 pm); its length corresponds, however, to C(sp2) = N(sp3) bonds (127.9-132.9 pm). Diazomethane is planar (C2v symmetry). The IR spectrum of diazomethane is characterized by the strong NN stretching band (2102 cm"1 in the gas phase, 2075 cm"1 in the solid state, 2096 cm"1 in Ar or N2 matrices, Moore and Pimentel, 1964 a, 1964 b and references cited therein). Moore and Pimentel's two papers are still, in spite of their age, an excellent account of the IR spectrum of diazomethane. They also include measurements and discussions of the three isotopically-labeled diazomethanes CHDN2, CD2N2, and CH215N14N. Fadini et al. (1978) measured the CN and NN stretching bands of the three isotopic diazomethanes CH214N2, CH214N15N, and CH215N14N. They were found at the following wavenumbers: CN 1136, 1112, and 1170 cm"1; NN 2097, 2075, and 2073 cm"1, respectively. More recently, Vogt et al. (1984 b) recorded the NN stretching band of gaseous diazomethane by means of an interferometer and a tunable diode laser spectrometer. With that equipment, the structure of the band was resolved for the first time, and nine subbands were analyzed. The recording was made with a resolution of 0.07 cm"1. At room temperature, diazomethane is a yellow gas. The electronic spectrum in the gaseous state has two maxima, a very weak one at 410 nm (e « 3 L mol"1 cm"1, with a long tail of diffuse bands on the bathochromic side) and a more intense maximum at 215-217 nm (e > 104) (Brinton and Volman, 1951; Herzberg, 1966, p. 530; Bastide and Maier, 1976). The vacuum UV spectra (135-200 nm) of gaseous diazomethane and deuterated diazomethane were recorded by Merer (1964). Suhr's (1963) early measurements and those of Koster and Danti (1964) of the chemical shift in the *H NMR spectrum (8 = 3.20 and 3.34 ppm, respectively, i.e., at ca. 1.9 ppm higher field than ethene) indicated that NMR is an interesting technique for diazoalkanes. Indeed, 13C and 15N NMR spectra of diazomethane and its derivatives provide useful information on the electronic structure. The chemical shift of the C-atom (5 = 23.3 ppm, relative to TMS, Albright and Freeman, 1977) shows a peculiarly high-field resonance relative to isoelectronic compounds with H2C(sp2)= groups like ketenimines (Firl et al., 1975), 1,2-dienes (Runge and Kosbahn, 1976) and nitrile oxides (Christl et al., 1973). Only ketenes show shifts to even higher field (Olah and Westerman, 1973; Firl and Runge, 1974). The valence force constant /(NN) was calculated by Fadini et al. (1978) to have a value that corresponds, on the basis of Siebert's formula (1966), to an NN bond order of 2.66. Analogously, the CN bond order was calculated to be 0.913. The coupling force con-

148

5 The Structure of Aliphatic Diazo Compounds

stant /(NN/CN) = 0.0191 mdyn/pm indicates a strong interaction between the two stretching frequencies. The dipole moment of diazomethane was measured by Cox et al. (1958). The surprisingly small value of 1.50 ± 0.01 D is consistent with the unusually low force constant obtained by Moore and Pimentel (1964 c) in their evaluation of out-of-plane CH2 bending frequencies in the IR spectrum of diazomethane. All these physical data on diazomethane are explainable with the conclusion that this compound is a mesomeric hybrid of structures 5.1 a, 5.1 b, and 5.1 c, with a decreasing importance in that sequence. Moore and Pimentel (1964 c) calculated the theoretical dipole moments for 5.1 a to be 5.46 D and for 5.1 b to be 6.24 D (with opposite signs). They deduced from these values that 5.1 a predominates over 5.1 b. From these data only, the mesomeric structure 5.1 c is actually not necessary. It was, however, added a long time ago (e. g., Eistert, 1938) because of the reactivity of N(2) as an electrophilic center (for other mesomeric structures see Sect. 4.4, 4.32a-4.32e).

X

C = N=N

-+

\\

*•

X

C —N=N

-«

^

5.1 a

^

c —N=N

H

5.1 b

5.1 c

Several experimental results obtained with substituted diazomethanes, however, cannot be understood with the hybrid structures 5.1a-5.1c only. The discussion of substituted derivatives will allow a more sophisticated interpretation of the electronic structure of diazoalkanes. It is surprising that, to the best of our knowledge, X-ray structures have only been published for diazomethanes in which the two H-atoms are replaced by a hydrocarbon, namely 2-bromo-9-diazofluorene (5.2; Griffiths and Hine, 1970) and 9-diazofluorene (5.3; Tulip et al., 1978). There is also an X-ray analysis of the heteroaromatic diazo compound 3-diazoindazole (5.4; Leban et al., 1978).

5.2

X = Br

5.4

5.3 X = H

In addition, X-ray analyses were made for several diazo ketones that we will discuss later in this section, and also analyses of several diazoalkanes and ethyl diazoacetates containing a group bonded to the C(l) atom by heteroatoms (i. e., Si, Hg, Pb, Pd, and Zn; see Regitz and Maas, 1986, Table 1.1, p. 9, and Lorberth et al., 1991). 2-Bromo-9-diazofluorene (5.2), 9-diazofluorene (5.3), and 3-diazoindazole (5.4) have bond lengths comparable to those of diazomethane; NN 112.4 (±0.4) pm, 112.5

5.2 Diazoalkanes and Related Compounds

149

(±0.4) pm, and 111.0 (±0.3) pm, respectively; and CN 132.5 (±0.4) pm, 132.4 (±0.4) pm, and 133.8 (±0.3) pm, respectively (Griffiths and Hine, 1970, R = 0.09; Tulip et al., 1978, R = 0.044; Leban et al., 1978,.R = 0.049). In comparison with other NN and CN bond lengths mentioned in the discussion of the structure of diazomethane earlier in this section, it can be stated that these three diazo compounds show a type of bond and charge delocalization similar to that of diazomethane. ll,12-Bis(diazo)-ll,12-dihydroindeno[2,l-0]fluorene (5.5) may be considered as a representation of an (almost) 'doubled' 9-diazofluorene. It was obtained by Sugawara et al. (1984) as green needles with double absorption maxima at 490 (e = 36) and 568 nm (e = 16 L mol"1 cm"1), suggesting strong through-space interaction between the two diazo chromophores. Ready formation of an aromatic cyclic azine (5.6) is further evidence for the close proximity of the two diazo groups in 5.5. These conclusions were supported by the X-ray crystal structure (Miyazaki et al., 1991). The indeno[2,l-a]fluorene moiety is planar, the N atoms deviate slightly from the plane in order to avoid the strain caused by the short contact between the N-atoms. Their through-space distance is shorter (300 pm) than the sum of their van der Waals radii.

(5-1)

With respect to IR spectra, we will concentrate the discussion of substituted diazomethanes to significant differences in the NN stretching frequency relative to that of diazomethane (2075-2102 cm"1, depending on measuring conditions, see above). Several alkyldiazomethanes display frequencies in the region 20302080 cm"1 in CC14 (Yates et al., 1957; Day et al., 1966; and others), e.g., 4-diazooctane 2050 cm"1. Perfluorinated diazoalkanes display higher frequencies. They are indicative of a higher contribution of the carbanion-diazonium mesomeric structure of type 5.1 b, as shown by bis(trifluoromethyl)diazomethane and bis(perfluoroethyl)diazomethane (2137 and 2119 cm"1, respectively; Gale et al., 1966). A similar effect was found by Ciganek (1965 a) for dicyanodiazomethane, for which the anionic charge mesomerism as indicated in 5.7 seems to be a reasonable explanation. Replacing one or both H-atoms by phenyl groups in diazomethane results in small, but probably understandable shifts of the NN stretching frequencies to lower values:

150

5 The Structure of Aliphatic Diazo Compounds

diazophenylmethane 2062 cm"1, diazodiphenylmethane 2042 cm"1 (Foffani et al., 1960). We shall return to these two compounds in the context of their electronic spectra before we discuss their structure on the basis of 13C- and 15N NMR spectra.

- Nixc— iW 5.7

The IR spectrum of diazocyclopentadiene has been discussed by Zollinger (1994, Sect. 4.2). As stated above, diazomethane is yellow. Homologous diazoalkanes are slightly more reddish, e. g. , diazoethane Amax = 450 and 470 nm (double peak, Brinton and Volman, 1951 ; Bradley et al. , 1964). The colors of mono- and diphenyldiazomethane and their aryl-substituted derivatives are, however, strongly shifted to the more bathochromic side, i. e. , to red and purple shades. The absorption bands of monophenyldiazomethane (Amax = 491, 275 nm; e = 26, 22000 L mol"1 cm"1, respectively), diphenyldiazomethane (Amax = 526, 288 nm; e = 101, 21300 L mol"1 cm"1, respectively) and (4-methoxyphenyl)diazomethane (Amax = 507, 276 nm; e = 27, 29000 L mol"1 cm"1, respectively) are representative examples (Kirmse and Horner, 1959; Closs and Moss, 1964). These bathochromic shifts in the spectra of mono- and diphenyldiazomethane suggest that aromatic groups on the C-atom of diazomethane do something else to the electronic structure than just enhancing the contributions of mesomeric structures of the type 5.1 b by delocalizing the partial negative charge from C(l) into the aromatic ring(s). This fact also becomes evident in the 15N NMR chemical shifts of N(l) and N(2). As observed by Roberts' group (Duthaler et al., 1978), these compounds show substantial downfield shifts of 13-20 ppm and 41-45 ppm for N(l) and N(2), respectively, relative to diazomethane (in diethyl ether and cyclohexane, upfield from 1 M H15NO3 in D2O, see Table 5-2). As sugggested by Roberts and his coworkers, these shifts are compatible with a contribution of the mesomeric structure 5.8. It is known that diphenylmethylcarbenium ions 5.9 are characterized by large bathochromic shifts in their electronic spectra relative to the corresponding diphenylethanes, as shown by Zollinger's group (Bernasconi et al., 1973).

C—N=N 5.8

5.2 Diazoalkanes and Related Compounds

151

In Table 5-2, representative results of 13C and 15N NMR measurements of various diazo compounds are given (Duthaler et al., 1978). The 15N(1) and 15N(2) NMR chemical shifts are at rather low field relative to those of arenediazonium ions. This is in contrast to the 13C NMR chemical shifts of C(l). These 13C NMR shifts correlate well with those of the corresponding C-atoms of the appropriate carbanions ()CH~, n = 5, slope = 0.40, r = 0.994) but surprisingly also with the shifts of the corresponding hydrocarbons ()CH2, n = 6, slope = 1.05, r = 0.997)*. The underlying cause of these correlations still has to be explained. Diazocyclopentadiene and its tetracyano derivative were discussed previously in the context of arenediazonium ions (Zollinger, 1994, Sect. 4.2, p. 79 f). Table 5-2. 13C and 15N NMR chemical shifts of C(l)-atoms and N-atoms of diazo compounds (data from Duthaler et al., 1978). Compound

6 i3C(l) a)c)

5 KN(l) b)c)

6 i5N(2)b)c)

H2C=N2

23.3

90

-14

H5Q£H=N2

47.2

76.8

-62.5

(H5C6)2C=N2

62.3

70.7

-65.5

HAX /> f

57.7

92.7

-32.0

63.2

89.0

- 65.0

72.2

106.2

*£/

\ ^xx^^

92.6

147.1

41.6

79.8 102.1-115.8 123.0

117.1 146.8-150.2 152.2

9.6 50.8-57.2 57.1

a

) Downfield from TMS in ppm. > Upfield (+) and downfield (-) from external 1M H15NO3 in D2O. c ) Solvents etc. see Duthaler et al. (1978).

b

* Mono- and diphenyldiazomethane were not included in these correlations.

152

5 The Structure of Aliphatic Diazo Compounds

It is instructive to plot 15N against 13C chemical shifts, as carried out by Zollinger's group (Grieve et al., 1985) for the data given in Table 5-2 and for some additional compounds. Figure 5-2 clearly demonstrates, that 15N and 13C shifts help classification of these compounds in two distinct groups, those with a dominant diazonium structure and those with a predominantly diazoalkane structure. Structurally interesting derivatives of diazoalkanes are those substituted at C(l) by a carbonyl group, in particular the a-diazo ketones. Wolff (1900, 1902, 1912; Wolff and Hall, 1903) who synthesized them first, assumed originally a structure of a 1,2,3-oxadiazole (5.11) for a-diazo ketones (5.10).

yA 5.10

5.11

A valence tautomerism between 5.10 and 5.11 should not be neglected completely (see Zollinger, 1994, p. 74). Positive evidence for the open structure 5.10 comes, however, from X-ray investigations on a-diazoketones. Structures were determined by X-ray measurements for only a few compounds, but the results clearly state that they have basically the structure 5.10. Hope and Black (1972) evaluated the X-ray data of l,4-bis(diazo)butane-2,3-dione (5.12) and found the following bond lengths and bond angles: C(1)-N(1) 131.3pm, N(1)-N(2) 111.4pm, C(2) = O(l) 122.2pm, C(1)-C(2) 141.8 pm, C(1)-N(1)-N(2) 176.8°, N(l) - C(l) - C(2) 116.5°, C(2)-C(3)-0(1) 125.2°, C(1)-C(2)-C(3) 114.0° (R = 0.029, < j = l p m ) * . The molecule has a center of symmetry in the crystal. H

OH)

C(4) = N(3)=N(4)

N(1)=Cm

0(2)

H 5.12

The C(2)-carbonyl and the N(l)-diazo group are in the (Z)-configuration, the C(2)and C(3)-carbonyl groups in the (^-configuration. The NN distance is slightly shorter than the corresponding distance in diazomethane, but somewhat longer (but not statistically significant) than that in aromatic diazonium ions. The N(l) — C(l) distance is, however, shorter than that of aromatic diazonium ions but not clearly different from that in diazomethane. The distance C(l) - C(2) is shorter than a con* For R factors, crystallographic atom numbering and SI units, see introduction to Sect. 4.2 in Zollinger (1994).

110

120

•

•

110

„• % 100

oR

OH

90

70

C Chemical Shift, ppm ^n

13

80

^

60

'\ 50

40

30

—

Fig. 5-2. Correlation of 15N and 13C NMR chemical shifts of C(l) and N(oc) of arenediazonium ions and diazo compounds (after Grieve et al., 1985). H, NO2, OH, CH3 and OCH3 indicate the unsubstituted and 4-substituted benzenediazonium ions. C(l) is the C-atom to which the diazo or diazonio group is linked.

150

i? 130

6

CD

1

CO

*f

a 90

E

70

9

Ho2

g 5r

3

*

a.

§

154

5 The Structure of Aliphatic Diazo Compounds

jugated C(sp2)-C(sp2) single bond (145.5 pm, Allen et al., 1987), but longer than a C(sp2) = C(sp2) bond in compounds with the structural element C=C — C = O (134.0 pm, Allen et al., 1987). The C(2) = O(1) bond length corresponds to that of the carbonyl group in compounds C = C - C = O (122.2 pm, Allen et al., 1987). In conclusion, it is likely that each part of this "dimeric" a-diazo ketone has a structure based on the mesomeric structures 5.13 a, 5.13 b and 5.13 c. Analogous conclusions can be drawn from the X-ray structure of l-diazo-2-phenylethan-2-one (co-diazoacetophenone; Aliev et al., 1985).

H

H

5.1 3a

H

5.1 3b

5.1 3c

The mesomeric structure 5.13 c indicates that (Z)/(E>isomerism is likely because of the double-bond character of the C(l) - C(2) bond. We will discuss that question below in the context of NMR spectra. The X-ray structure determination of 2-diazo-l,2-diphenylethan-l-one ('azibenziP, 5.14) was accomplished by von Schnering et al. (1986). Relative to l,4-bis(diazo)butane-2,3-dione longer CN and NN bonds (134.3 and 112.4 pm, respectively), a shorter carbonyl bond (120.8pm) and a remarkably longer C(1)-C(2) bond (147.3 pm) were reported. The two phenyl groups are configurated (E) to each other. s

/C — C

CH— CH2CH2— O— Cx

X

°'

C6H5

5.14

^

\ 5.15

The natural product azaserine (O-diazoacetyl-L-serine, 5.15, Fusari et al., 1954 a, 1954 b; Moore et al., 1954; Nicolaides et al., 1954) was analyzed by Fitzgerald and Jensen (1978) and gave results consistent with those mentioned above. There are also X-ray structure determinations available for cyclic compounds containing an a-diazocarbonyl grouping. In 3-diazocamphor (3-diazo-l,7,7-trimethylbicyclo[2.2.1]heptan-2-one, 5.16; Cameron et al., 1972, R = 0.056, a = 0.7 pm), the CO and NN distances and the CNN angle are in the range of values obtained with open chain a-diazo ketones. The CN distance (129.6 pm) is somewhat shorter. 5-Diazo-6-methoxy-5,6-dihydrouracil (5.17) and its tricyclic derivative 2'-deoxy-5-diazo6-hydro-O6,5/-cyclouridine were investigated by Abraham et al. (1971). The various interatomic distances are similar to those summarized above. Bond angles were not reported (R = 0.056 and 0.052, respectively, a = <0.7 pm). 3,6-Bis(diazo)cyclohexane-l,2,4,5-tetraone (5.18) is an interesting borderline case between l,3-dicarbonyl-2-diazocycloalkanes and quinone diazides (5.19, also the 1,2-isomer). We discussed the latter compounds in the book on aromatic diazo com-

5.2 Diazoalkanes and Related Compounds

155

5.17

pounds (Zollinger, 1994, p. 70). Quinone diazides have bond lengths of the CC bonds adjacent to the carbonyl group and to the diazo group in the range 139-146pm, and slightly shorter CC bonds between CH groups (136-137pm). Ansell (1969) made an X-ray investigation of the bisdiazo-tetraone 5.18 (R = 0.079, o = 1.0 pm). All CC distances are longer than those in a quinone ring, but the CC bonds at the C-atoms with the diazo group are shorter (143 pm) than those of the 1,2- and 4,5-CC bonds (154 pm). They are all longer than C = C bonds in cyclohexadienones (133.3 pm, Allen et al., 1987). The widening of the ring angles at the Catoms with the diazo groups is very large (129.0°), and all the other ring angles are small (114.4-114.9°). The NN distance seems to be slightly longer than normal for diazonium ions (110.7 pm), but the difference is hardly significant. These results indicate, therefore, that 5.18 has practically no aromatic character, but 5.19 has. Therefore, the bis(diazo)-tetraone can be considered as a "cyclic dimer" of a l,3-dicarbonyl-2-diazoalkane.

O

A similar, but more complex, case is 3-diazo-2,3-dihydrophenalene-l,2-dione-l-(4'bromophenylsulfonyl)-hydrazone (5.20), which was investigated by Maas et al. (1982).

5.20

156

5 The Structure of Aliphatic Diazo Compounds

Apart from the possibility of valence isomerism 5.10^5.11, geometrical isomerism between (Z)- and (£>forms (e. g. , 5.21 and 5.22, below), and two types of keto-enol tautomers (5-2) and two diazo-nitrile imine tautomers (5-3) is also conceivable. OH r*

RCH2

x~x

RCH2

'

<5'2>

XHN2

OH ,<X

O

H

RCH2

O

The presence of such equilibria was indicated, because the electronic spectra of adiazo ketones display isosbestic points in mixtures of nonpolar and hydroxylic solvents when the solvent ratio was changed (Miller and White, 1957). In aprotic solvents l-diazo-propan-2-one has a dominant band at 245 nm. In ethanol, the intensity of this band decreases by 15% and a new strong band appears at 273 nm (Csizmadia et al., 1969; Yates et al., 1975). Similar spectral changes are also found, however, in a-diazo ketones without acidic H-atoms in the a-positions to the carbonyl groups (Fahr, 1959). These changes cannot, therefore, be due to tautomeric equilibria such as (5-2) or (5-3). We shall return to keto-enol equilibria, however, later in this section. As suggested by Fahr and investigated by Foffani's group (Pecile et al., 1964), the solvent dependence of the UV spectra of diazo ketones is due to hydrogen bonding of the protic solvent with the O-atom of the carbonyl group. These authors also found that in IR spectra the strong carbonyl stretching frequency, observed at 1662 cm"1 in apolar solvents, decreases significantly in intensity in the presence of phenol and bands at 1643 and 1633 cm"1, which are very weak in pure apolar solvents, become more intense with increasing phenol concentration. These observations may be explained by a decreased CO bond strength if a hydrogen bond )C = O--HOC6H5 can be formed.

5.2 Diazoalkanes and Related Compounds

157

The greater weight of the mesomeric structure 5.13 c in a-diazo ketones causes a shift of the NN stretching frequency to higher values by ca. 30-40 cm"1 relative to diazoalkanes. 2-Diazo-l,3-diones show even larger shifts (see examples given by Regitz and Maas, 1986, in Table 1.8). The partial double-bond character of the C(O) — C(N) bond, as visualized by the mesomeric structure 5.13 c, is the reason why it is feasible that stable (Z)- and (£)-isomers 5.21 and 5.22 exist.

° 5.21

5.22

Experimentally, the existence of these isomers was demonstrated by Sorriso's group (Paliani et al., 1976) by examining the NN stretching band of various a-diazo ketones in CC14. Indeed, the following compounds showed two bands: 1-diazopropan-2-one (2088 and 2107 cm"1), 3-diazobutan-2-one (2068 and 2087 cm-1) and 3-diazo-l,4-diphenylbutan-2-one (2071 and 2088 cm"1). A series of other a-diazo ketones, however, showed only one band, e. g. , diazoacetophenone. IR spectra were also used in investigations of 2-diazo-l,3-diones and interpreted assuming mixtures or predominance of one isomer (Nikolaev and Popik, 1989 a). The criterion of the number of NN stretching bands is, however, not safe for a decision with respect to the presence of a (Z)- and an OE>isomer. Cyclic diazo ketones like 2-diazocyclohexanone (5.23) and 3-diazobicyclo[2.2.1]heptanone (5.24, diazonorcamphor) can exist only as (Z)-isomers because of their ring geometry. Nevertheless, both compounds are characterized by two IR bands in the region of the NN stretching frequencies, (5.23): 2080 and 2230cm- 1 ; 5.24: 2080 and 2140 cm"1; Bassani et al., 1974). As these wavenumbers indicate, there is a greater difference between them than between those quoted above from Sorriso's work, and there are other cases in the literature where the spectrum shows another band, separated from the NN stretching band by an even larger gap, but where the occurrence of both rotamers is unlikely for other reasons (e.g., Regitz et al., 1979).

N2 5.23

5.24

The two rotamers can be detected by comparing experimental dipole moments with calculated values (see Piazza et al., 1968, Sorriso and Foffani, 1973, and the summary by Sorriso, 1978, p. 120). By using this method, Nikolaev and Popik (1989b) found that l-aryl-3-methyl-2-diazo-l,3-diones undergo a (ZfE)^(EtE)

158

5 The Structure of Aliphatic Diazo Compounds

equilibrium, in contrast to the l,3-diaryl-2-diazo-l,3-diones, which occur as (Z,Z)-rotamers. Proton, 13C, and 15N NMR spectra probably provide less ambiguous results on rotamer equilibria of diazocarbonyl compounds in solution, but only at low temperature (*H: Kaplan and Meloy, 1966; Wentrup and Dahn, 1970; Kessler and Rosenthal, 1973; Curci et al., 1974; 13C: Zellhofer, 1980; 15N: Lichter et al., 1977). The NMR results show that, at the temperatures given in parentheses, the only diazoaldehyde investigated (2-diazoethan-l-one) consists of 31% (E)- and 69% (Z)-isomer ((E)/(Z) = 0.449 (253 K)), whereas in a-diazo ketones the (Z)-isomer is much more dominant (l-diazopropan-2-one, (E)/(Z) = 0.082 (233 K)) (Kaplan and Meloy, 1966, *H NMR in DCC13). If the methyl group of l-diazopropan-2-one is substituted by a chlorine atom or a phenyl group, the (£)-isomer can no longer be detected (Kessler and Rosenthal, 1973, in CD2C12 at 173 K). Under the same conditions, substitution by a 2,4,6-trimethylphenyl group results in an (£)/(Z)-ratio of 0.32. As the 2,6-methyl groups force the phenyl ring out of the C(O)-CH-N 2 plane, one has to conclude that n — n overlap C6H5 — C(l) is responsible for the extreme dominance of the (Z)-isomer in diazoacetophenone (2-diazo-l-phenylethan-1-one). If C(l) or C(l) and C(3) in l-diazopropan-2-one are substituted by alkyl, phenyl, or other groups, the (E)-form is dominant or even the only detectable isomer. The X-ray structure determinations, discussed earlier in this section, demonstrate that the configuration in the solid state is that expected from studies in solution. Nevertheless, one should not generalize that rule on the basis of the small number of structure determinations made with crystals. In diazo esters almost equal amounts of the two rotamers were found (methyl diazoacetate: (£)/(Z) 0.859, ethyl diazoacetate 0.840, both at 223 K in CDC13, Kessler and Rosenthal, 1973). The activation energy for isomerization from the (Z)- to the (^-isomer is in the range 65-75 kJ mol"1 for diazo ketones and 38-52 kJ mol"1 for diazo esters (Kaplan and Meloy, 1966; Kessler and Rosenthal, 1973). Another isomerization problem of a-diazo ketones and a-diazo aldehydes is the question whether the corresponding diazoenols in Scheme 5-2 can be detected. To the best of our knowledge, no experimental or theoretical investigations have been carried out on the capability of a-diazocarbonyl compounds to form diazoenols. In the chemistry of enols in general, impressive advances have been made since the late 1970's, as shown clearly in the volume on enols in the Patai series, edited by Rappoport (1990). As an example, the enols of the simple compounds acetaldehyde and acetone, ethenol (vinyl alcohol), and prop-l-en-2-ol, were assumed for many decades to exist on the basis of various reactions typical for these carbonyl compounds. They were, however, generated independently and characterized only in 1976 by Saito and in 1982 by Holmes and Lossing, respectively. Considering that these molecules were elusive for a very long time, a surprising number of synthetic methods have been developed for them since 1976 (see review of Hart et al., 1990). On that basis, the present author is moderately optimistic that, one day, the enol of an a-diazo aldehyde or an a-diazo ketone may be generated and characterized. The precise information now available on keto-enol equilibria of simple enols, on the influence of substituents and on cyclic carbonyl compounds, together with recent work on sim-

5.2 Diazoalkanes and Related Compounds

159

pie unsaturated diazo compounds, will be helpful. Some less favorable indications will be presented, however, in the following paragraphs. The diazo group of a-diazocarbonyl compounds has some diazonio group character (5.13 b and 5.13 c). This indicates the presence of electron-withdrawing inductive and mesomeric effects, which are comparable to analogous effects in a-nitroand a-cyano ketones. Experimental and theoretical investigations (reviewed by Toullec, 1990) demonstrate that the nitro and the cyano groups destabilize the keto form by inductive electron withdrawal and mesomeric stabilization of the enol. In ethanol or water, the enol content of a-cyano ketones is much higher than in apolar solvents, e.g., for 2-oxo-l,2-diphenylpropanenitrile no enol was detectable in hexane, but 70% was found in ethanol. It may be speculated, therefore, that a diazo group has an analogous effect as shown in the keto -enol equilibrium (5-4).

Vc"° X

N/

R

O

V 5.25

+

N2

The resulting enol 5.25 contains cumulative double bonds at the diazo C-atom. Structure 5.25 is comparable to propadienol (5.27), the enolic isomer of prop-2-enal (5.26), which was synthesized by Capon et al. (1985). H

\

/° X

H2C^

H

5.26

H

/OH

/

H'

\ 5.27

The comparison indicates that the enol of an a-diazocarbonyl compound may be a (relatively!) stable entity. Unfortunately, however, the situation looks less favorable on the basis of our present knowledge on diazoethene (5.28). As discussed in Section 2.9, 2,2-dialkyl derivatives of this compound are likely to be formed in reactions of ketones with dimethyl diazomethylphosphonate (2-95), but they lose N2 very rapidly. The resulting unsaturated carbenes can be trapped or undergo a 1,2-alkyl shift to give 1,2-dialkylethynes. 2,2-Difluorodiazoethene, however, is detectable at a

160

5 The Structure of Aliphatic Diazo Compounds

5.28

steady-state concentration of 2% when 3,3-difluoropropadienone is photolyzed in an N2 matrix (Brahms and Dailey, 1990; see Sect. 2.9 for experimental aspects, Sect. 5.3 for theory). As an N2 matrix is not a polar medium favoring enols with electron-withdrawing a-substituents, we conclude that these factors increase the difficulties associated with detecting the enol form of an a-diazocarbonyl compound. This discussion of the potential existence of enols of a-diazocarbonyl compounds brings us to the structure of alkenediazonium ions. The mesomeric structures 5.13 b and 5.13 c of an a-diazocarbonyl compound have a similarity with alkenediazonium ions (5.29a-5.29b). Scheme 5-6 shows one of Bott's synthetic routes to alkene diazonium salts (see Sect. 2.10).

_c/

// O

(C2H5)30+

^\N

2

(5-6)

SbCI6-

H5C20/ 5.29a

5.29b

Returning to the enol problem for a moment, it is very unlikely that this reaction starts under superacidic conditions with a deprotonation at the a-C atom, forming the common base of the diazo ester and its enol. The introduction of the second ethyl in 5.29 is unlikely to be an alkylation of the enol. Bott (1985) reported, however, an observation that strongly indicates the presence of the deprotonated form of the alkenediazonium salt 5.30. If this salt is kept with 0.05 equiv. OCD3~K+ for 20 h in the perdeuterated solvent mixture (CD3)2SO - CD3OD (5:2), almost complete exchange of the a-H for D is observed, but no nitrogen is evolved. It is likely that this exchange represents an acid-base equilibrium (5-7). The conjugate base 5.31 of this reaction is structurally related to the enol 5.25 with (at least) partial cumulative double bonds at the C(a)-atom! A structural problem of alkenediazonium ions, which is similar to that of adiazocarbonyl compounds, is the potential existence of rotamers around the CC bonds. Due to their double bond character based on the mesomeric structure 5.29 a, two rotamers are expected. Indeed, in the *H NMR spectrum of 5.29 the signals of the two ethyl groups appear separately (Szele et al., 1983). In perdeuterated nitrobenzene, the methylene signals of the ethyl groups are already coalesced at room temperature, but the methyl groups absorb as two triplets separated by 22.15 Hz (at 90 MHz). The coalescence temperature is 350 ± 5 K, corresponding to a rotation barrier of 75-77 kJ mol"1, which is, therefore, significantly higher than that of

5.5 Theoretical Investigations

161

CH3

N

CH3 / \ /H(D) C=C

N

f CH3

V

B(C6H5)4-

+ CD30^ in CD3OD *- CD 3°-

t

\ CH3 A I

+ CD3OD(H)

(5-7)

CH3 / C=C — N2+

5.30

N7 CH3 5.31

diazo esters (38-52 kJ mol"1, see above) and indicates a higher double bond character, similar to that of ketene acetals (5.32, Sandstrom, 1983). Lebedev (1991) published an extensive review on the mass spectrometry of diazoalkanes, diazo ketones, diazo esters, cyclic diazo compounds (including diazoquinones), and related compounds.

"W RO

R"

5.32

5.3 Theoretical Investigations on Aliphatic Diazonium Salts, and on Alkane, Alkene, and Alkyne Diazo Compounds Theoretical work on aliphatic diazo compounds has been published for a long time. Initially such investigations were particularly promising on diazomethane. The limited computer facilities available in the 1960's gave relatively meaningful results with this small molecule. Later, more sophisticated ab initio techniques allowed more complex problems to be handled, e.g., explanation of the instability of certain substituted diazoalkanes. We will discuss work on diazoalkanes, diazoalkenes, and related compounds first and investigations on aliphatic diazonium ions later in this section.

162

5 The Structure of Aliphatic Diazo Compounds

The three first semiempirical investigations on diazoalkane structures (bond lengths, bond angles and electron densities) were made by Owen (1961), Schuster and Polansky (1965) using the HMO method, and by Hoffmann (1966), who applied the EHMO technique. We will not enumerate other publications based on various semiempirical methods that were conducted during the following ten years because they have been reviewed extensively by Moffat (1978a)*. That year also marked the more intensive use of ab initio methods after their first application by Andre et al. (1969). That first investigation was, however, invalidated because of an error in geometry. In 1978 two key papers using the ab initio basis were published. Moffat (1978 b) investigated diazomethane and seven derivatives of diazomethane; Vincent and Radom (1978) compared methanediazonium ion and benzenediazonium ion. The latter paper will be discussed later in this section; however, we mention it here together with Moffat's work because both publications are, even today, a must for study by scientists interested in the theory of diazo compounds. Moffat used ab initio single configuration calculations on the minimal STO-3G basis for bond lengths, bond angles, gross atomic charges and total electronic energies for the following diazoalkanes: N2CH2, N2CHF, N2CF2, N2CHCH3, N2C(CH3)2, N2CHCN, diazopropyne (N2CH - C = CH3), and diazocyclopentadiene (N2CC4H4). Calculated NN bond lengths vary from 117.5 pm for diazocyclopentadiene to 119.0 pm for diazomethane, and to 122.6 pm for difluorodiazomethane. Charge distribution in diazomethane can be summarized in the formula [H2C] +0-086[N2] -°-086. In the two fluorinated diazomethanes the charge on the diazo group is more negative and more concentrated on the N(/?)-atom. Diazoacetonitrile and diazocyclopentadiene, however, are calculated to have positively charged diazo groups. The total electronic energy of diazomethane was found to be -378 kJ mol"1; for all the other diazoalkanes the energy values are more negative, culminating in —883 kJ mol"1 for difluorodiazomethane. In all cases the highest occupied molecular orbital is a n orbital perpendicular to the plane of the molecule. There is a fairly large number of theoretical investigations on diazoalkanes, particularly on diazomethane, in the context of reactions of these diazo compounds, e. g., on the use of diazoalkanes as 1,3-dipoles in cycloadditions or the rearrangement of diazomethane into its isomers. We will return in later chapters to such papers in the discussion of these reactions. A remarkable investigation that is, in a certain sense, a continuation of Moffat's work discussed above, is McAllister and TidwelPs evaluation (1992b) of substituent effects on diazomethane by ab initio calculations using the Hartree-Fock method with geometry optimization and energy calculations using the 6-31G* basis set and the Monstergauss program. McAllister and Tidwell calculated energies of diazomethane and of 19 monosubstituted derivatives (5.33), values for the energy

* In the monograph of Regitz and Maas (1986, p. 12) only such theoretical investigations on diazoalkanes are (very briefly) reviewed that were published before the mid 1970's.

5.3 Theoretical Investigations

163 (5-8)

differences of the isodesmic reaction* (5-8) and of the isomerization of the corresponding diazirine into the diazoalkane**. In my opinion, McAllister and TidwelPs paper is remarkable for two reasons, first, for the discussion of the correlation of the data to those obtained earlier by TidwelFs group on the effect of substituents on ketenes (5.34; Gong et al., 1991), which are isoelectronic with diazomethanes, and on diazocyclopolyenes (5.35, n = 1-3; McAllister and Tidwell, 1992 a). The second reason is the fact that the authors are able to describe and to discuss their work on less than two journal pages!

=N=CH— R

O=C = CH—R

5.33

5.34

The energy exchange in the isodesmic reaction (5-8) is a valuable measure of energy differences t±E due to electronic charges, since the number and types of bonds are unchanged. For diazoalkanes 5.33, just as for ketenes 5.34, McAllister and Tidwell found a linear correlation between AE and the substituent group electronegativities KBE (Boyd and Edgecombe, 1988; Boyd and Boyd, 1992). The diazoalkanes are stabilized by electropositive groups (R = Na > Li > BH2 > A1H2 > MgH > Be > SiH2 > CH = O > PH2, etc.) and destabilized by electronegative groups (F > OH > Cl > NH2 > CF3). Most interesting are the deviations from the linear relationship: There are positive deviations for Tt-acceptor groups, particularly for R = CH=O and BH2, indicating mesomeric stabilization of these species, as shown in 5.36a-5.36b. This result is well known for the relatively high stability of adiazocarbonyl compounds. Negative deviations were found for R = HO and NH2. The geometries with coplanar OH and NH bonds, respectively, were calculated to be less stable than the twisted conformations 5.37 and 5.38 in which lone-pair donation to the diazomethane function is minimized. This destabilization by 7i-donation is also analogous to that found for ketenes (Gong et al., 1991). We will return to the stereochemistry of diazocarbonyl compounds later in this section.

_ C = N=N H

"

C — N=N H

5.36a

5.36b

* Isodesmic reactions are processes in which not only the number of electron pairs is held constant but also formal chemical bond types are conserved, and only the relationships among the bonds are altered. ** For the diazoalkane-diazirine equilibria, see Sect. 5.4.

164

5 The Structure of Aliphatic Diazo Compounds

5.37

5.38

In conclusion, McAllister and TidwelPs work (1992 b) clearly demonstrates the influence of electronegativity and conjugation on the stability of diazoalkanes. In the other paper of McAllister and Tidwell (1992 a), the authors reported on the use of the same techniques as in the investigation on substituted diazomethanes (1992 b) for a comparative study of diazocycloalkenes, namely diazocyclopropene (5.35, n = 1), diazocyclopentadiene (n = 2), and diazocycloheptatriene (n = 3) with the corresponding fulvenes (5.39, n = 1-3) and ketenes (5.40, n = 1-3).

5.39

5.40

The three series of cyclic diazo compounds, fulvenes and ketenes show analogous effects*. They are manifested in isodesmic-energy comparisons, dipole moments, atomic charges and bond lengths, calculated as discussed above for McAllister and Tidwell's investigation of monosubstituted diazomethanes (5.33). In all three series the most stable compound is the derivative with the five-membered ring (n = 2), the cyclopropenes and the cycloheptatrienes are less stable. The stabilization and destabilization are due to the aromatic character of the cyclopentadienes and the antiaromatic properties of the cyclopropenes and the cycloheptatrienes. Among other results of the calculations the aromaticity-antiaromaticity effect is elegantly demonstrated in the comparison of calculated CN and NN bond lengths of diazocyclopropene and diazocyclopentadiene and those of the corresponding compounds with a cyclopropyl and a cyclopentaenyl ring (Fig. 5-3): The last two compounds mentioned have calculated CN and NN bonds that are within the limits of normal diazoalkane bond lengths (see Fig. 5-1 for diazomethane, and Allen et al., 1987, for other diazo compounds). The calculated bond lengths in diazocyclopropene and diazocyclopentadiene however, are, significantly different from those for "normal" diazoalkanes and correspond, in the case of diazocyclopentadiene, fairly well to a recent experimental determination derived from the microwave spectrum (Sakaizumi et al., 1990: CN = 130.0 pm, NN = 113.9 pm). Those of diazocyclopentadiene are intermediate between those of a diazoalkane and arenediazonium ion — a result that is not surprising as we know since Doering and DePuy's classical investigation (1953) that this compound has reaction characteristics that are similar to those of aromatic diazonium ions (see Sect. 2.6, * For a more extensive discussion on ketenes and their relations to diazoalkanes, see the monograph of Tidwell on ketenes (1995).

5.3 Theoretical Investigations

165

134.9 123.2

116.0

145.1

130.0 144.1

125.0 153.8

112.7 N= N

145 3

'

Fig. 5-3. C-N and N-N bond lengths (in pm) of some cyclic diazo compounds, calculated by McAllister and Tidwell (1992 a).

and Zollinger, 1994, pp. 309 and 342). Diazocyclopropene is the reverse case: nothing is known experimentally that indicates a similarity to diazonium ions. It is well known from experimental data that a-diazo-/?-ketones and >ff-diazo-a,ydiketones are, in general, more stable than diazoalkanes lacking a carbonyl group in a neighboring position (see Sect. 5.2, 5.13 a-c). Yet, the stability is also influenced (negatively) by twisting the diazocarbonyl fragment, e. g. , as shown in comparisons of open-chain diazo ketones with cyclic analogs (see Nikolaev et al., 1991, and Popik and Nikolaev, 1993, and references there). Such distortions were investigated by Goodman et al. (1994) with the help of molecular mechanics calculations. Their paper contains structural results for distortions of seven diazo ketones and diazo diketones. The MM2 modeling program is based on force field parameters developed from a combination of X-ray data, IR spectroscopy, and ab initio and semiempirical calculations. The results showed that X-ray data and calculated geometries could be compared only after allowance for the effect of crystal packing forces. Valence bond (VB) calculations were performed on diazoalkanes by Walsh and Goddard in 1975. They concluded from their combination of ab initio generalized valence bond and configuration interaction that the structure of diazoalkanes has to include some singlet biradical character with strong bonding between the radical n orbitals on the C(a)-atom and on the N(/?)-atom resulting from the interaction with the 7i pair on the N(a)-atom (5.41).

C — N=N* \/'

5.41

In the context of the recent renaissance of the VB theory distortion of atomic orbitals has been studied to avoid zwitterionic structures (Cooper et al. , 1987) *. For the case of diazomethane in such a VB treatment, the N(a)-atom becomes hypervalent since it takes part in five covalent bonds, i. e. , a net double bond with the C-atom * For a recent paper of Cooper's group see Cooper et al., 1994.

166

5 The Structure of Aliphatic Diazo Compounds

and a net triple bond with the N(/?)-atom (Cooper et al., 1990). It is claimed that this treatment can also be applied to 1,3-dipolar cycloadditions of diazoalkanes *. A similar VB-based hypothesis on the structure of diazoalkanes has been developed by Trinquier and Malrieu (1987). On that basis, the authors postulated a distortion of the molecule in a trans-bent way, with angular N—N —C and nonplanar N-CR 2 arrangements**. Horan and Glaser (1994) calculated the proton affinity of diazomethane by a series of increasingly sophisticated levels of an initio theory. Their best value (883 k J mol"1) is within experimental results. We shall discuss that work of Horan and Glaser in our review of theoretical investigations of the methanediazonium ion later in this section. Horan and Glaser (1994) calculated the proton affinity of diazomethane by a series of 14 very sophisticated MO methods. Their best value (883 kJ mol"1) is within experimental results. We shall discuss that work of Horan and Glaser in our review of theoretical investigations of the methanediazonium ion later in this section. We add to the discussion of diazoalkanes some remarks on mono- and difluorodiazomethane. As mentioned above, Moffat (1978 b) calculated extreme values for the total electronic energy and for the NN bond length of difluorodiazomethane. McAllister and Tidwell (1992 b) came to the analogous conclusion that fluorine substituents have an extremely destabilizing influence on diazomethane. Boldyrev et al. (1992) found that mono- and difluorodiazomethane are not viable species as no barrier could be found for these compounds against exothermic dediazoniation. We shall discuss these compounds in the following section on isomers of diazomethane, as difluorodiazirine is known. There we shall also discuss diazosilane (SiH2N2) and its isomers. As mentioned in Section 2.9, diazoethene (5.42, X = H) is interesting because it is isoelectronic with propadienone (5.43), but until today only difluorodiazoethene (5.42, X = F) has been observed (Brahms and Dailey, 1990). Therefore, diazoethenes are interesting targets for theoretical investigations. After a semiempirical study of difluorodiazoethene (Lahti, 1987) on the basis of MINDO/3 and MNDO calculations, Lahti's group (Murcko et al., 1988) investigated the parent compound in ab initio MP2/4-31G and MP2/6-31G* structural optimizations. It was found in these two approaches that diazoethene is expected to be bent (CCN angle 117.3-117.8°). This result is rather unfamiliar for a cumulene-type molecule, but consistent with

5.42

5.43

i5.44

* Hypervalent structures have been discussed also on the basis of MO theory by Pople's group (Kahn et al., 1987a). See also footnote 13 in the paper of Horan and Glaser (1994). ** No numerical data on the geometry are presented in Trinquier and Malrieu's paper.

5.5 Theoretical Investigations

167

analogous results for propadienone. The MP2/4-31G optimized structure calculations of Brahms and Dailey (1990) resulted in the doubly-bent structure 5.44. It is consistent with an analysis of the IR spectrum. As mentioned in the introductory remarks to this section, the year 1978 is characterized by two key investigations each based on ab initio calculations of diazomethane (Moffat) and of methanediazonium ion (Vincent and Radom). We start the discussion, therefore, on alkanediazonium ions with their paper*, which concentrates on methane- and benzenediazonium ion (for a review of the latter, see Zollinger, 1994, pp. 84 ff). The study was carried out with minimal (STO-3G) and split-valence (4-31G) basis sets. Two structures with a bridging C-atom constrained to lie on the perpendicular bisector of the NN bond were included in the calculations. The NN bond lengths for the open and the two bridged structures were calculated to be 113.9 pm and 115.5 pm respectively, with the STO-3G basis set, and 107.9 pm and 108.5 pm, respectively, with the 4-31G basis set. For the N2 molecule these two basis sets yield bond lengths of 113.4 pm and 108.5 pm, respectively. Experimental values for the methanediazonium ion are not known, but experience with arenediazonium ion clearly indicates that the NN distance is not significantly larger in diazonium ions than in the N2 molecule (see Zollinger, 1994, pp. 67 ff). The authors interpret this result by an orbital interaction diagram that demonstrates the primary interaction between an essentially lone pair HOMO orbital on N2 with the lowest LUMO orbital of the methyl cation, which is the 2p orbital at C+ . As the HOMO of N2 is not heavily involved in bonding within the N2 fragment, this interaction does not result in a significant change in the NN bond length on formation of the methanediazonium ion. In contrast to the benzenediazonium ion the CN bond (151.3 pm with 4-31G) is slightly longer than a "normal" CN single bond (146.9 pm in alkylamines, see Allen et al., 1987). Vincent and Radom also calculated the binding energy for the open and the bridged structures as the difference in energy between these structures and separated N2 and methyl cation. The bridged structures were found to have very low binding energies (<21 kJ mol"1); the binding energy of the open structure was calculated as 117-216 kJ mol"1 (depending on basis sets used). We will not discuss them further, as this difficult problem was solved much later with better results. A very instructive investigation of the structure of the methanediazonium ion was performed by Wiberg and Breneman (1990), who calculated structures of 35 monosubstituted methanes. Their analysis is based on 6-31G** wave functions, which have been calculated by using 6-31G*-optimized geometries. The main interest was the distribution of electron population among the atoms in these molecules, for which they used Bader's theory (1985, 1990, 1991) of atoms in molecules. Wiberg and Breneman found surprisingly good linear correlations for the charge density path between atoms and various structural parameters, in particular with the location of the point of minimum charge density on that path, called the bond critical point. Among the 20 compounds with threefold symmetry the methanediazonium ion is the species with the highest charge density at the CH bond critical point. The CN and NN bond lengths were calculated to be 105.96 pm and 107.28 pm, respectively. Previous semiempirical treatments are reviewed by Vincent and Radom (1978).

168

5 The Structure of Aliphatic Diazo Compounds

Earlier Glaser (1989) investigated diazonium ions theoretically and demonstrated that the classical Blomstrand-Hantzsch notation (see Zollinger, 1994, pp. 2 and 64, R — ISI = N, also called Lewis-Kekule formula) does not represent the electron density well. In following papers (Glaser, 1990; Glaser and Choy, 1991; Glaser et aL, 1991) this result was corroborated. Particularly important and interesting for that conclusion was an investigation on the basis of Bader's theory (Glaser et aL, 1992 b) that included the methanediazonium ion, but, in addition, nine other inorganic and organic diazonium ions (see Table 5-3). Comparative studies in that group of cations XN^ are on a safer basis than the comparison of the methanediazonium ion with 19 other monosubstituted methanes investigated by Wiberg and Breneman because among them is only one other cation (methaneammonium ion) in addition to 15 neutral compounds, two anions, and a zwitterion. Glaser and coworkers were interested first of all in the stability of the X — Na bond, i. e. , in the dediazoniation energy. Their calculations are not, however, based only on the difference between heats of formation of XN^ and the sum of heats of formation of X+ and N2, but on what they call fragment transfer energies. For the determination of the energies of the fragments in the molecules, they used Bader's theory, which is based on a partitioning of the molecular electron density distribution into atomic regions, the basins, the means of properties of the gradient vector field of the electron density. With this partitioning, kinetic energies of the fragments (kEi and AE2) can be calculated. Examples of this notation are (5-9) and (5-10), the sum of which corresponds to the dediazoniation energy (AEdiss, 5-11). N2

X[(XNN)+]

AE

* >

X+

AEi + AE2 = AEdiss

(5.9)

(5-10) (5-11)

The sums of the transfer energies &E\ and AE^ the directly calculated RHF/6-31G* dissociation energies, as well as the integrated charges of the XN^ ions (1C) are given in Table 5-3. The differences between these two SCF energy values reflect the numerical accuracy of the determination of the atomic energies via integration. As can be seen, these differences are rather small and of no consequence for the conclusions. It is well known that the accurate determination of binding energies requires the consideration of electron correlation effects, and the best values reported are also included in Table 5-3. The charges on the diazonio groups show that the positive charge is concentrated mainly on the hydrocarbon fragment, not only in the case of the methanediazonium ion but for all other diazonium ions with C — N linkages. However, this is true only in part for the inorganic representatives — a "full" cationic charge on the diazonio group was calculated to be present in the fluorodiazonium ion! Glaser's work disclosed further insights and correlations: the transfer energies of process (5-9) A^ are in all cases negative (&E\ = —23 to —1640 kJ mol"1), except

5.3 Theoretical Investigations

169

Table 5-3. Dediazoniation energies and integrated charges (1C) of the diazonio group of XN2+ ions according to Glaser et al. (1992 b). XN2+

AE,

FN2+ HON2+ H2NN2+ H3CN2+ H5C2N2+ H3C2N2+ HC2N2+

A£dissa)

IC(N2) A£j + AE2

direct

Affdiss "best value"

-1641.9 -941.1 -309.0 -164.8 -330.1 -23.2 186.9

1.055 0.736 0.372 0.161 0.158 0.077 -0.007

653.3 378.7 215.8 108.8 24.2 75.8 177.7

668.1 372.9 215.8 108.9 24.2 75.3 179.1

852.7b) 526.8b) 333.5b) 192.0c) 61.1c) 119.2d) 367.8d)

840.6b) 505.0b) 307.9b) 171.lc) 41.0c) 95.4d) 347.3d)

-401.9

0.223

304.4

304.5

293.3 e)

274.1e)

-159.0

0.117

-12.5

-20.5

-15.1

e)

-30.1e)

-59.0

0.018

105.9

107.0

141.0°

121.8°

^

H2N C6H5N2+ a

> Unless stated otherwise, RHF/6-31G*//RHF/6-31G* values are given (kJmor1; Glaser et al., 1992 b). The "best values" are binding energies that include electron correlation corrections. The A//diss values are determined using the best values for AEdiss but also include corrections for vibrational zero-point corrections. b > MP4(SDTQ,fc)/6-311G**//MP2(full)/6-31G* + 0.9.AVZPE(RHF/6-31G*), Glaser and Choy,1991. c > MP4(SDTQ,fc)/6-311G**//MP2(full)/6-31G* + 0.9.AVZPE(RHF/6-31G*), Glaser et al., 1991. Data for methane- and ethanediazonium ions are for the highest common level used in that paper. For recent state-of-the-art computations of the binding energy of methanediazonium ion, see Horan and Glaser, 1994, and discussion in the text. d > MP4(SDQ,fc)/6-31G*//RHF/6-31G* + 0.9.AVZPE(RHF/3-21G), Glaser, 1989. e ) MP4(SDQ,fc)/6-31G*//RHF/6-31G* + 0.9.AVZPE(RHF/3-21G), Glaser, 1990. ° MP3(fc)/6-31G*//RHF/6-31G* + 0.9.AVZPE(RHF/6-31G*), Glaser and Horan, 1995.

that for the ethynediazonium ion (HC = C-N 2 + ). This means that the diazonio groups are destabilized in the diazonium ions compared with free N2. This destabilization increases as the electronegativity of X increases. The N2 transfer energies are fairly well correlated with the N2 charges (Glaser et al., 1992 b, Fig. 1). The slope of that correlation represents the average negative ionization energy of the dinitrogen molecule (ca. 1521 kJ mol"1). Correlation effects may affect the magnitude of the values of b£\ , but it has been argued convincingly that electron

170

5 The Structure of Aliphatic Diazo Compounds

correlation changes the differences between the fragment transfer energies and the charge of N2 presents strong evidence that the ionization potential of the diazonio group in a molecule essentially equals the ionization potential of free N2. In 1993 Glaser and Choy published a full paper on the electron density distributions (at the RHF/6-31G* level and including electron correlation at the MP2(full)/ 6-31G* level) in the heterosubstituted systems XN/ (X = F, HO, H2N) and compared these systems with methanediazonium ion. The results show that the positive charge on the N(/?)-atom is always larger than that on N(a). The N(a)-atom may even carry a negative charge! Unconnected structures of electrophile and dinitrogen must be considered for adequate representation of the density distribution in XN^. In the preceding discussion of the methanediazonium ion we did not enumerate all experimental and theoretical values published for the C —N binding energy. As there are three different values within the group of experimentally determined energies as well as more than three values calculated from theoretical basis, Horan and Glaser (1994) recalculated the reaction energy for the process CH3+ + N2 -> CH3N^ using full fourth-order M011er-Plesset perturbation theory, configurational interaction theory (CID, CISD), quadratic CI theory (QCISD, QCISD(T)), Gaussian-1 (Gl) and Gaussian-2 (G2) theory, and coupled cluster methods (CCD, CCSD, ST4CCD, CCSD(T)) with large basis sets (6-31G* 6-311 + G**, 6-311G(2df,p) and others), with and without inclusion of vibrational zero-point energies (VZPE). The expert will realize that these calculations are based on recent advances of theoretical methods for a sophisticated evaluation of electron correlation effects; they were possible only with appropriate hardware. The result is a table with 14 sets of total energies for the methanediazonium ion, for diazomethane, the methyl cation and dinitrogen, as well as of the binding energy of the methanediazonium ion (Eb) and of the proton affinity of diazomethane (PA). Horan and Glaser consider as best values: Eb = 184 kJ mol"1, PA = 883 kJ mol"1*. The calculated binding energy of methanediazonium ion is practically identical with the classical experimental value of Foster et al. (1974). McMahon's group determined the binding energy two times (McMahon et al., 1988; Glukovtsev et al., 1994). The second investigation was made in collaboration with Radom and resulted in a new value of E^ = 184 kJ mol"1 in truly outstanding agreement with the prediction of Glaser and Horan. Very interesting is the result that the dissociation energies of higher homologs of methanediazonium ion are much smaller. In 1986, Ford calculated dediazoniation energies for methane-, ethane-, and propanediazonium ions with semiempirical (MNDO, AMI) and ab initio procedures. The dediazoniation enthalpies at 25 °C are found to be, at the MP3/6-31GV/HF/6-31G* level, 159, 46, and 42 kJ mol-1, respectively. The significant difference between methane- and ethanediazonium ions has been explained by Glaser et al. in 1991 based on reduced electrostatic contributions to the CN bonding in the ethane derivative. The different stabilities may be the reason for observations in DNA alkylation, namely that methylation occurs preferentially at N centers of DNA, and that ethylation differentiates significantly * Horan and Glaser consider triple excitations as important. Therefore, the best values given above are mean values of those calculation methods which include triple excitation only.

5.3 Theoretical Investigations

111

less between the N and the O nucleophiles (see, e.g., Lown et al., 1984; Yuspa and Poirier, 1987). Ford's paper of 1986 and an earlier theoretical investigation of Ford (Ford and Scribner, 1983) had an important influence on the experimental work on dediazoniation mechanisms: it suggested to Kirmse to reinvestigate the stereochemistry of deaminations (Brosch and Kirmse, 1991) because theory was not consistent with the classical experiments of Streitwieser and Schaeffer (1957 a), who found significant amounts of racemate in the deamination product of [l-2H]-l-butylamine. The reinvestigation by Brosch and Kirmse using a new and better method for stereochemical analysis of product led to the surprising result of practically complete inversion of configuration (see Sect. 7.3 for details). This development is indeed a very gratifying case of a scientific development in which theory triggered an experimental reinvestigation of a reaction, the result of which was not in accordance with theory. Hegarty's group (Malone et al., 1988) investigated, in an ab initio study, addition of hydrogen atoms to the N(a)- and N(/?)-atoms of methanediazonium ions. The energy surface was determined at the UHF/3-21G level, and the relative energies were estimated at the UMP4SDQ/6-31G** level. The addition to the central (Na) atom exhibits an appreciably larger energy barrier than that to the terminal (N^) atom. The transition state of the latter reaction is only marginally bent. After the transition state, a bifurcation of the pathway leads to (Z)- and (E)-isomers of the product. In addition to ethenediazonium ion, which was included in the extensive investigation of ten diazonium ions by Glaser et al. (1992 b, see Table 5-3 above), Glaser 's group (Glaser et al., 1992 a, 1992 c; Chen et al., 1993) studied also alkenediazonium ions with substituents in the /^-position, i. e. , compounds that were synthesized and investigated experimentally by Bott and others (see Sects. 2.10 and 9.5). Glaser's work concentrated on 3-diazonioprop-2-enoic acid, for which the two (Z)-ro tamers 5.45 and 5.46, and the two CE>rotamers 5.47 and 5.48, are feasible. Ab initio calculations on restricted Hartree-Fock basis including electron-correlation effects handled by M011er-Plesset perturbation theory to second- and third-

.\

^

,

vv

Vtfc-S\

5.45

5.46

VC—C," ^

/c— o 5.47

\C = C \/ 5.48

172

5 The Structure of Aliphatic Diazo Compounds

order with 3-21G and 3-21G* basis sets gave the result that the (Z)-rotamer 5.45 is 7.8 kJ mol"1 more stable than 5.46. For the (E>rotamers, 5.47 was found to be 4.1 kJ mol"1 more stable than 5.48. A challenging problem is the question whether theory is able to detect any neighboring group interaction in the (Z)-rotamers between the diazonio group and the O-atom of the carboxy group. In aromatic diazo chemistry it was found that distortions in 3-carboxylatonaphthalene-2-diazonium zwitterion, in corresponding diazonium salts, and in quinoline-8-diazonium 1-oxide tetrafluoroborate may be due to an attractive interaction between the diazonio-N(a)-atom and the carbonyl Oatom, and between the N(/?)-atom and the counter ion (for literature and discussion, see Zollinger, 1994, pp. 72 and 73). Glaser's general result for all investigated organic diazonium ions, however, is the slightly negative charge on the N(a)-atom. A consequence would be, of course, that simple electrostatic attraction cannot be the cause of those effects. The geometry calculations of the (Z)-rotamers 5.45 and 5.46 made by Glaser et al. (1992d) gave the result that the angle 8 in 5.45 is smaller (123.5°) than in 5.46 (129.0°, both with 6-31G* basis set). An analogous effect is calculated for the angle e. For the conjugate base of 5.45 and 5.46, i.e., the diazonio-carboxylate, the calculated angle 8 (124.0°) is not smaller than that in 5.45. These results are not compatible with electrostatic N---O attraction only. They are clearly different from those found for the aromatic diazo compounds mentioned above. The authors propose a bonding model that is based on the electron densities. Electron density calculations also allowed a deeper understanding of the geometry of the two 2,2-disubstituted ethene-1-diazonium salts of which Glaser's group (Glaser et al., 1992c; Chen et al., 1993) made X-ray structure analyses (see Sect. 5.1). As discussed in Section 2.11, alkynediazonium ions have been postulated as metastable intermediates several times, but the first successful preparation of such a compound was reported only ten years ago (Helwig and Hanack, 1985). Alkynediazonium ions might be possible precursors for ethynyl cations, i.e., for C(sp)-centered carbocations. Early calculations of Glaser (1987) at the HF/6-31G* and the MP2/6-31G* levels indicated a very high CN binding energy (627 kJ mol'1) and, therefore, Glaser considered the stability of the ethynediazonium ion as too high for dediazoniation to occur. As shown in Table 5-3, the binding energy obtained with more sophisticated methods (Glaser et al., 1992b) is calculated to be significantly lower (177-179 kJ mol"1), but still higher than that of alkane-, alkene-, and arenediazonium ions. Diphosphonium ions (5.49), the phosphorus analogs of diazonium ions, are unknown, and of the PN ions 5.50 and 5.51 two aromatic compounds were reported by Niecke et al. (1988 a, 1988 b), and Curtis et al. (1994) described the gas phase generation of methylphosphoazonium ion. Glaser et al. (1992 a, 1993 b) investigated the three types of phosphorus analogs 5.49-5.51 (R = CH3) with ab initio techniques at the RHF/6-31G* MP2(full)/ 6-31G(df,p), and MP3/6-31GVRHF/6-31G* levels. Stabilities, spectroscopic properties, and electronic structures (1992 a) and the potential energy surfaces and elecR—p=p 5.49

R—N=P 5.50

R—P=N 5.51

5.4 homers of Diazomethane

173

tronic densities (1993 b) were calculated, the latter also for the phenylated analogs (R = C6H5). The results suggest that methanediphosphonium ion (5.49) and methanephosphazonium ion (5.50) should be stable ions that can be formed by addition of P2 and PN to methyl cation in the gas phase. The methaneazophosphonium ion (5.51) is predicted to isomerize easily into 5.50. Charge distribution is qualitatively best represented by 5.52-5.54. + R— P==P 5.52

5f 8- &f R-*-N=P

?" 5R— P=N

5.53

5.54

For the protonation of P2 and PN we refer to the discussion in Section 3.1, as these are purely inorganic compounds. Schindler (1987 b) tried to use IGLO correlation effects (IGLO = individual gauge for localized molecular orbitals) to calculate the magnetic susceptibility and NMR chemical shifts of N-containing compounds. For NN multiple bonds, however, the results were not satisfactory. The first step of the polymethylene formation was studied with ab initio techniques at RHF/3-21G by Chen and Ning (1993). The results indicate a two-step reaction for the formation of ethene (5-12). The intermediate is calculated to have a structure that is similar to an aziridine. The authors do not discuss whether that intermediate and the ethene will continue polymerization. :CH2(1A) 2

+ CH2N2

-

^ H2C-CH2

5.4 Isomers of Diazomethane In addition to the various interesting characteristics of diazomethane with respect to structure and reactivity, this smallest organic diazo compound attracted the attention of organic, physical, and theoretical chemists because it is isoelectronic with a variety of other molecules and anions and because of its isomers. Diazomethane possesses 16 valence shell electrons. This is also the case for two other molecules of similar structure and reactivity: dinitrogen oxide (O = N = N) and ketene (H2C = C = O). We have already discussed the similarity to ketene in Section 5.3. Furthermore, diazomethane is also isoelectronic with species that have little in common with its structure and reactivity, namely carbon dioxide, nitryl ion (NO2+), hydrogen azide, azide ion (Nf) and, of course, the structural isomers of diazomethane. Interest in isomeric diazomethanes started in 1934, i. e., even before Boersch (1935) clearly corroborated the structure of diazomethane itself (see Sect. 5.1). Miiller and Kreutzmann (1934) hydrolyzed diazomethyllithium 5.55 in ether suspension at

174

5 The Structure of Aliphatic Diazo Compounds

-80°C with an aqueous solution of a weak acid, e.g., potassium dihydrogen phosphate or ammonium chloride. By evaporation of the solvent mixture at - 50 °C in vacuo they obtained a pale yellow liquid that they called isodiazomethane (5-13). The same product can be obtained with the sodium salt and the triphenylmethylphosphonium salt [(C6H5)3£CH3] of diazomethyl anion. The yellow liquid is very unstable: decomposition starts on heating to 15 °C, and the compound explodes at ca. 35-40°C (Mtiller and Ludsteck, 1954; Miiller and Rundel, 1955). The tautomerization of diazomethane was originally assumed by Miiller et al. (1965) to lead to formonitrile imine (5.56, usually called simply nitrile imine), but they did not, however, explain the lack of 1,3-dipolar reactivity expected for such a compound. This problem was later solved by Mtiller et al. (1968). *H NMR demonstrated the structural equivalence of the two hydrogens and, therefore allowed, the structure of aminoisonitrile (7V-isocyanamide, 5.57) to be assigned to that isomer. Catalysis by KOH easily causes reisomerization of 5.57 to diazomethane. It is uncertain, however, whether nitrile imine (5.56) or only the common anion 5.55 of nitrile imine and diazomethane or another possible intermediate is involved in this two-step tautomerization (see, however, Hart, 1973).

5.55 H2O

I

-

*

HC = N=NH

T -<

^

-

~ 1

HC = N—NH

:Cr=N—NH2 ^

?

(5-13)

J

5.56

^ :c=N—NH2 5.57

The structure of isocyanamide was confirmed by the analysis of the millimeterwave spectrum by Schafer et al. (1981). Schwarz and coworkers (Goldberg et al., 1994) were able to show very recently that nitrile imine (5.56) is stable in the gas phase. It can be generated in a beam experiment by neutralization-reionization mass spectrometry neutralizing the radical cation HCNNH + '. The same authors also calculated the structures and energetics of nitrile imine by a hybrid method of Hartree-Fock and density functional theory (DFT). It is possible to replace both H-atoms of diazomethane by silver (Blues et al., 1974) if an ether solution of diazomethane is treated with a solution of silver acetate in pyridine (see also Sect. 9.1). The crimson disilverdiazomethane (5.58) yields diazomethane when hydrolyzed in an aqueous solution of KCN. In addition to isocyanamide (5.57) two other isomers of diazomethane have been characterized: diazirine* (5.59) and cyanamide (5.60). * The present author does not recommend calling this compound cyclic diazomethane, as done by McBreen et al. (1992).

5.4 Isomers of Diazomethane

175

Ag X C=

N=N

^

N \=>N CH2

5.58

H2N-C = N

5.59

5.60

For cyanamide, no rearrangement into diazomethane is known for obvious structural reasons. Diazirine, however, is the most interesting isomer of diazomethane in various respects. As discussed briefly before (Sect. 5.1), a cyclic structure was originally proposed by Curtius (1889) for ethyl diazoacetate and other aliphatic diazo compounds. In 1960, however, Paulsen and, in the following years, Schmitz and Ohme (1961 a-c), and Graham (1962) achieved the first synthesis of diazirine*. As Scheme (5-14) shows, they used methods that are completely independent of diazomethane. With ammonia and hydroxylamine-O-sulfonic acid (or NH2C1 with an oxidant such as tert-butyl hypochlorite, ^C4H9OC1), formaldehyde (for monoand disubstituted diazirines other aldehydes and ketones, respectively) forms diaziridine (5.61, originally called an isohydrazone), which is then dehydrogenated to diazirine with silver oxide or bichromate (5-14).

H2C=0

%, '

> H2C^|.. -^*

H2CCII

(5-14)

NH3 + f-C4H9OCI

The general chemistry of diazirine, as far as it is related to the present subject, has been discussed by Liu (1982, 1987), Moss (1989), Creary (1992), Cameron et al. (1992) and others. Graham (1962) described a direct one-step synthesis of diazirine by the reaction of difluoroamine (HNF2) with tert-butyl- or octyl azomethine (H2C=N —R) in CC14 solution in a vacuum system. A yield of 62% was reported without any further information on mechanistic details. It seems that dealkylation and defluorination take place in the transient l-alkyl-2-fluoro-diaziridine (5.62, 5-15). Later, various modifications and other syntheses for diazirine and substituted diazirines were developed (see Schmitz, 1984). The preparation of pentamethylenediazirine (5.63) has been described by Schmitz and Ohme (1973) in Organic Syntheses. Pierce and Dobyns (1962) verified structure 5.59 for diazirine on the basis of the rotational microwave spectrum in the frequency region 7.8-41 GHz. The NN, CN,

* The isomer discussed here is 3//-diazirine. As the other isomers are not related to diazoalkanes (and therefore not mentioned in this book) we use the term diazirine without prefix.

176

5 The Structure of Aliphatic Diazo Compounds

5.63

and CH distances, the bond angles, given in Fig. 5-4, and the dipole moment (1.59 D) were calculated from the data obtained with the isotopic isomers H213CN2 and H2C14N15N. The HCH and NCN planes are mutually orthogonal.

117° (

Cxgr

64.5° 122.8pm

Fig. 5-4. Interatomic distances and bond angles in diazirine (after Pierce and Dobyns, 1962; angles in the ring after Schmitz, 1984). The HCH and NCN planes are mutually orthogonal.

J

H NMR and IR results are consistent with this structure. A high resolution IR spectrum was interpreted by Winnewisser's group (Gambi, 1984; Gambi et al., 1984). Diazirine is a colorless gas with boiling point -14°C. The UV spectrum of the gas shows six well-separated bands between 301 and 324 nm (e308 = 176 L mol"1 cm"1, Graham, 1962). The mass spectra and appearance potentials of diazirine and diazomethane have been compared with each other by Paulett and Ettinger (1963 a). These results are consistent with more recent work of Winnewisser's group (Bogey et al., 1984; Vogt et al., 1984a) who recorded the microwave spectrum of diazirine in the more extended range of 8-400 GHz and interpreted both its fine structure and that of the 15N isotopomer. Diazirine can be stored in glass containers, although, as mentioned by some authors, it decomposes explosively in the presence of air and is also decomposed by ultra-violet light. In the presence of mineral acids, it decomposes slowly, whereas most diazoalkanes (including diazomethane) are not only very sensitive to mineral acid, but also to carboxylic acids. Valence isomerization of diazoalkanes into diazirines and vice versa is possible by photolysis, although it is always accompanied by dediazoniation. The photolysis of diazirines was investigated intensively in recent years (e.g., by O'Gara and Dailey, 1992, and by Modarelli and Platz, 1993; see also the book of Michl and BonacicKoutecky, 1990). An electronically excited state is obtained that can, in principle, decay by at least four competitive pathways (Scheme 5-16): a) fluorescence, b) intersystem crossing with the production of triplet carbene, c) formation of an excited diradical followed by internal conversion and production of singlet carbene, and d)

5.4 Isomers of Diazomethane

111

(5-16)

adiabatic rearrangement and subsequent intramolecular conversion to diazoalkane. In substituted diazirines containing at least one H(a)-atom, Modarelli et al. (1992) proposed that an additional competitive process involving a 1,2-H shift concerted with N2 extrusion is possible. Yamamoto et al. (1994) investigated the mechanisms of these carbene formations by MC - SCF calculations (see later in this section, Scheme 5-25). Elegant examples, which also demonstrate the difference in photochemical stability of the two isomers (as mentioned above), are 6,6,8,8-tetrafluoro-7-diazotridecane (5.64) and the corresponding 3,3-bis(l,l-difluorohexyl)diazirine (5.65). As shown by Erni and Khorana (1980), the photochemical isomerization of this diazoalkane into the diazirine (5.65) requires light of wavelength A = 410 nm, whereas the reverse isomerization is possible only with light of higher energy, namely A = 310 nm. It is also interesting to note that the dediazoniation by-products 5.66-5.68, which are typical reaction products of transient carbenes, are formed in both forward and reverse isomerizations *. 2=C(CF2— C5H11)2

. II/C(CF2-C5H11)2

< A = 310nm

5.64

Hx

CF2

A F-V\/

C

F 5.66

5.65

CsHii

4H9

H

(5-17)

N

Hx

CF2—C5H-n

'/\ F^./ \^

H

F

/^2

C

F2C=Cv

C4H9

5.67

5.68

The by-products 5.66-5.68 are very likely to have been formed via the diazoalkane. This question cannot, however, be answered accurately, as Erni and Khorana did not mention yields obtained in an experiment starting with the diazoalkane. Work conducted in the 1960's by Prey's group (summary: Frey, 1966) demonstrated that the * For photolytic isomerization of the perfluorinated 3-diazobutan-2-one at 10 K in an Ar matrix see Laganis et al. (1983).

178

5 The Structure of Aliphatic Diazo Compounds

mechanisms of competitive photolyses of diazirines to dediazoniation products via diazoalkanes or directly are very complex. These mechanisms were investigated in more detail using kinetic methods and isotopic labeling by the groups of Liu and of Stevens and by others. As this is a borderline problem within the scope of this book, we will concentrate on only a few representative examples. In the liquid-phase photolysis of pentamethylenediazirine (5.63) Steven's group (Bradley et al., 1977) showed by experiments in CH3COOD that 59 % of the diazirine decomposed via the diazonium ion (5-18) and 41 % via the carbene (5-19).

•#, : * 5.63 ' CH3COOD

(5-18)

- CHgCOO-

OCOCH3 (H29)5

alkene

)C^

(H29)5

^N 5 63

'

(5-19) (H29)5

carbene products

With 3-butyl-3-phenyldiazirine, however, Liu et al. (1981) found that the photolysis in CD3COOD proceeded only via mechanism (5-18), without any participation of the carbene intermediate. Experiments with 3-benzyl-3-chlorodiazirine in CD3COOD and CD3COOD-CC14 mixtures (Liu et al., 1984) can be explained with the mechanism (5-20) involving only the carbene intermediate. Yet with 3-phenyl-3-(trifluoromethyl)diazirine (5.69),

5.4 homers of Diazomethane

179

-N2

insertion of CD3COOD

H5C6-CH2x /OCOCD3 C C\ c

(Z) and (E)

/\

X

H(D)

+ CDgCOcr

photolysis is accompanied by the formation of l-diazo-2,2,2-trifluoro-l-phenylethane (5.70) (Brunner et al., 1980) in contrast to the thermolysis of 5.69, where Liu et al. (1986) did not detect the diazoalkane 5.70. A kinetic investigation gave results that are consistent with the mechanism (5-21), i.e., with a carbene-dinitrogen intermediate *. F3CX

11N

X

5.69

(5-21)

Experimental evidence for the thermal isomerization from a substituted diazirine to the corresponding diazoalkane was also reported by Doyle et al. (1989 a). They used diazirines as stable diazoalkane precursors which, with the help of the catalyst rhodium(n) perfluorobutyrate, undergo carbenoid-type reactions. An example is reaction (5-22). Less competition is observed from side reactions that were dominant * For a comparable, but probably not strictly analogous complex of aryl cations and N2, see Zollinger, 1994, Sects. 8.3 and 8.4.

180

5 The Structure of Aliphatic Diazo Compounds

(5-22)*

H

CH2CH2CH3

when the diazoalkane was used directly or when the diazirine was used in the absence of the catalyst. Valence isomerizations of a-diazo ketones and the corresponding diazirines are also known. A particularly instructive case is the system 3-diazoindolin-2-one (5.71a)^spiro[diazirine-3,3'-indoline]-2'-one (5.72a), and TV-methyl derivatives, which were investigated by Voigt and Meier (1975).

hv

5-71

a: R = H b: R = CH3

'

»

- -

(5.23)

5.72

This system is interesting because of three characteristic phenomena, namely: 1) The photolysis of 3-diazoindolin-2-one (5.71 a, R = H) does not take place by irradiation at the most bathochromic band (A = 450 nm, shoulder with log e = 1.3), but at 290 nm, i.e., close to the band at Amax = 300nm (log e = 3.9). As discussed by Hoffmann theoretically on the basis of EHMO calculations in 1966, i. e., many years before this experiment was carried out, such a valence isomerization is likely to proceed only if a higher singlet (S2) is reached by irradiation. 2) That photolysis has a half-life f1/2 * 35 min (27 °C in CD3OD). The deconvolution of the spectra as a function of time shows that the diazirine 5.72 is formed as a transient intermediate with a maximum concentration of «13 mol-% after 20 min. 3) The reverse reaction is possible not only photochemically, but also thermally. This is due to the lower thermal stability of this diazirine relative to the compound without a carbonylamino group, i. e., pentamethylenediazirine (5.63, Schmitz and Ohme, 1973). This decrease in stability of 5.72 is likely to be due to the pseudoconjugation of the three-membered ring with the carbonyl group, decreasing the * This formulation is taken from Doyle et al. In the opinion of the present author, it does not unambigously explain the experimental results.

5.4 Isomers of Diazomethane

181

C-N bond order of the diazirine. One of the two C-N bonds is weakened (or cleaved) in the transition state, probably in a similar way to that indicated in the mechanism of reaction (5-19). In contrast to the photolysis, however, in the thermal reaction the second C-N bond becomes stabilized after dissociation of the first. That stabilization is due to conjugation of the diazo group with the carbonyl group in addition to the release of the strain energy of the diazirine ring, which was calculated by Polta and Thiel (1986) to be ca. 83 kJ mol"1. Therefore, the yield of 3-diazoindolin-2-one (5.71 a) is claimed to be practically quantitative, i. e., dediazoniation is negligible. In the photochemical reaction of the diazirines 5.72 (R = H or CH3) in CH3OH, however, the final products are, as shown in (5-24), 3-methoxy-oxindole (5.73 a) and 3-methoxy-l-methyloxindole (5.73b), respectively, with small amounts (<5%) of the isoindigos (5.75, R = H and CH3, respectively) and of the azines (5.76, R = H and CH3). By continuous irradiation the two methoxy-oxindoles 5.73 lose formaldehyde in a Norrish-II reaction to form the corresponding oxindoles (5.74).

5.72 a, b

hv (A>290nm) -N2

(5-24)

5 76a b

-

'

At an early date, Moore and Pimentel (1964 d) carried out photolyses of diazirine in a solid matrix of N2. They detected diazomethane, but concluded from results using a 15N2 matrix that diazomethane was derived from the reaction of primarily formed methylene with dinitrogen (for later work on reactions of other carbenes with N2 see Sect. 8.1).

182

5 The Structure of Aliphatic Diazo Compounds

Engel (1980) and Liu (1982) report in their reviews that the formation of diazomethane in the photolysis of diazirine is still controversial, in contrast to the photolysis of 3-substituted diazirines, where rearrangement into the respective diazoalkanes is unquestioned. In addition to the three well-characterized and identified isomers of diazomethane, cyanamide (5.60), 3//-diazirine (5.59), and aminoisonitrile (5.57) discussed earlier, six other isomers (see later in this section) are conceivable. It is, therefore, not surprising that all these isomers of diazomethane have attracted the attention of physical chemists interested in the experimental determination of heats of formation and in theoretical calculations of thermodynamic stabilities. From mass spectra and appearence potentials, Paulett and Ettinger (1963a, 1963b) estimated the heat of formation to be 331 kJ mol"1 for diazirine and 206 kJ mol"1 for diazomethane. In other words, diazirine is thermally less stable than diazomethane by 125 kJ mol"1. Shortly after these investigations, Bell (1964) suggested that the heats of formation should be calculated using a different set of assumptions, which resulted in lower absolute values, but still with the same difference between A//f for diazomethane and diazirine*. The first theoretical investigation of diazirine vs. diazomethane was carried out by Hoffman (1966), who used extended Hiickel MO calculations. His results, together with the experimentally determined geometries of Pierce and Dobyns (1962), showed that diazomethane is 120 kJ mol"1 more stable than diazirine. The ionization potentials were calculated to be 844 kJ mol"1 for diazomethane and 902 kJ mol"1 for diazirine. These results compare roughly with the experimental values of Paulett and Ettinger (1963a, 1963b) for these potentials (637 and 718 kJ mol""1, respectively). Other historically interesting investigations with remarkable good conformity with experiment are the SCF ab initio calculations of Snyder and Basch (1969), and Kochanski and Lehn (1969). Further theoretical investigations on diazomethane and on diazirine appeared after Moffat published his review (1978 a), e.g., those by Devaquet's group (Bigot et al., 1978), Moffat (1979), Cambi et al. (1984), Hori et al. (1984), Mueller-Remmers and Jug (1985), Chen and Tang (1988), Wiberg and Breneman (1990), Kramarenko et al. (1990), Kroeker et al. (1991) and a joint paper of Olivucci and Robb's groups (Yamamoto et al., 1994), which contains additional references from the early 1990's. We will not discuss these investigations here, with the exception of the last four papers mentioned, because they contain no results on other isomers and, partly, their results are not in agreement with others**. Wiberg and Breneman's paper (1990) is important for diazomethane (see Sect. 5.3), but less for a comparison with diazirine. We will first provide some elementary definitions for clarification and concentrate subsequently on the results of two relatively recent theoretical papers in which both, * See the discussion by Moffat (1978 a, p. 9, Table 8 and pp. 13-14). ** The paper of Chen and Tang (1988) contains a table of reaction energies of the diazomethane-diazirine isomerization calculated by nine different MO methods. The results vary between -531 and +132 kJ mol"1. The experimental value is +34 (±21) kJ mol"1 in favor of diazomethane (Halgren et al., 1978). See also the book of Michl and Bonacic-Koutecky (1990) for

5.4 Isomers of Diazomethane

183

diazomethane and diazirine together with seven other possible isomers of CH2N2, the corresponding silicon compounds SiH2N2, and the isomers of difluorodiazomethane (CF2N2) are compared on the basis of several MO methods. The present author has the impression from the literature on the stability of diazomethane relative to diazirine that two different physico-chemical phenomena were called (thermal) stability in some of the publications, namely the thermodynamic stability, as defined by the free energy of formation AG? and the free enthalpy of formation A//? for the (hypothetical) formation of a compound from the elements in a gas phase reaction under standardized conditions (298 K, 1 mol). AG? and A//? are related to one another by the free entropy AS? in the Gibbs-Helmholtz equation AG?= AT/f-TAS?. The absolute values of AG?, A//? and AS? do not give definite information on the stability of a compound, as this word is used in the everyday language of a chemist, because it is related to an unrealistic chemical process, namely the formation from the elements. If A//f is known, however, for a given compound and for a real product of one of its reactions, the difference in magnitude of the two free enthalpies tells us whether this reaction is likely to take place, but we cannot depict at all, at least in principle, the half-life of such a reaction. That second question is, therefore, a kinetic problem. Qualitatively, a chemist should differentiate between the two questions by saying, e. g., that compound XY has a low thermodynamic, but a high kinetic stability etc. Instead of "kinetic stability", the term "inertness" is recommended in some modern textbooks, e.g., that by Dickerson, Gray, Darensbourg and Darensbourg, "Chemical Principles" (1984; German ed., 1988). The term was coined originally by Taube (1952) for ligandexchange reactions of metal complexes. The compartmentalization in chemistry is probably the reason why this term is used only rarely outside inorganic chemistry * If inertness has to be defined in quantitative terms, the activation energy parameters (A^ or A//* and AS*) must be used. As they refer only to the rate of one specific reaction, they are, however, not a useful description of the term "inertness". The latter should be used, in our opinion, as a qualitative term, and quantitatively only for comparing two or more compounds (that are closely related structurally) in the same reaction by making reference to the rate constants or the activation parameters mentioned. Returning to the problem of the relative stabilities of diazomethane and its various isomers like diazirine etc., we emphasize that all previously mentioned heats of formation are free enthalpies of formation, but that the diazoalkane ^ alkyldiazirine isomerizations (5-17), (5-18), and (5-23) are cases of differences in inertness. We will now discuss several papers on the calculation of geometries and heats of formation of up to nine isomers of diazomethane, diazodifluoromethane, and diazosilane by using various MO methods. The first two papers were published by Thomson and Glidewell (1983) for CH2N2 and SiH2N2, and by Glidewell et al. (1987) for CF2N2. * I hesitate somewhat to give these rather elementary remarks on thermodynamic and kinetic stabilities, but experience in teaching organic chemistry and some cases of misunderstanding in discussions of specific diazo reactions in the (modern) scientific literature justify such remarks.

184

5 The Structure of Aliphatic Diazo Compounds

Of most interest from a general point of view is the fact that Glidewell and coworkers compared MO calculations with the ab initio SCF method* and calculations carried out with the MNDO method (Dewar and Thiel, 1977). GlidewelPs results are, therefore, not only interesting for the specific three sets of isomeric fiveatomic molecules discussed, but generally for a comparative evaluation of various MO methods. We will discuss first the series of the following nine compounds with the formula CH2N2; diazomethane (5.1), cyanamide (5.60), 3H-diazirine (5.59), isocyanamide or aminoisonitrile (5.57), nitrile imine or formonitrile imine (5.56), carbodiimide (5.77), iso- or l//-diazirine (5.78) and the carbene cyclodiiminomethylene, which may be a singlet (5.79 b) or a triplet (5.79 a). As mentioned in part earlier in this section, only the first four of these isomers are well known as isolated compounds. Derivatives of 5.77, 5.78, and isocyanamide (5.57) are known (Schafer et al., 1981), but the parent compounds are not; the two carbenes 5.79 b and 5.79 a have not yet been observed. H

\

\l— C = N

5.60

H

\

N=N \ /

5.59

+ _

N— N=C

5.57 HN— NH

H-N=C = N-H

HN

W/N CH

5.77

_

5.78

5.56 HN— NH

V

V

ft

tl

5.79 a

+

H— C = N=N— H

5.79 b

The calculated geometrical parameters for diazomethane (5.1) are in reasonable agreement with experimental data for all calculation methods. For cyanamide (5.60), it became clear from Vincent and Dykstra's study (1980) on the cyanamide -isocyanamide (5.57) rearrangement that SCF calculations without polarization functions predict a planar structure in agreement with experiment (i.e., N — C — N = 180°), and that additions of such functions result in a non-planar structure. Thomson and GlidewelPs results (1983) show that the deviation from planarity is appreciable only for the 4-31G* geometry (178.3°), but the C = N bond is too short by 2.5 pm relative to the experimental value. The MNDO method shows the best agreement with experimental data. For diazirine (5.59), the 3-21G and MNDO calculations agree reasonably well with experiment (no results for the other levels have been reported). The results for isocyanamide (5.57) parallel those of cyanamide, except that SCF calculations give a small deviation from planarity. In nitrile imine (5.56) and carbodiimide (5.77) a reasonable agreement of the structural parameters with those of Houk's group (Caramella et al., 1977 a) and Moffat (1979) was found; nitrile imine is predicted to be planar. The last three isomers (5.78- 5.79 b) have such a high energy of formation that the values reported for their geometrical parameters * Using the split-valence 3-21G basis set and by including electron correlation by the MP3 method (Pople et al., 1976) on the 3-21G and the 6-31G* basis sets.

5.4 Isomers of Diazomethane

185

are doubtful. For instance, the calculated NH bond length of 1/f-diazirine (5.78; 101.8-102.3 pm instead of an average of 100.9 pm given in the tables of Allen et al., 1987) does not correspond to that of a stable ring system. Particularly interesting in the context of this book are the calculated heats of formation of the nine isomeric structures mentioned above. They are given in Table 5-4. Table 5-4. Enthalpies of formation (A//f) of CH2N2 isomers, relative to cyanamide (kJ mol"1) for different basis sets (Thomson and Glidewell, 1983).

Diazomethane (5.1) Cyanamide (5.60) Diazirine (5.59) Isocyanamide (5.57) Nitrile inline (5.56) Carbodiimide (5.77) Isodiazirine (5.78) Carbene singlet (5.79 b) Carbene triplet ( 5.79 a)

MNDO

3-21G

6-3 1G*/ 3-21G

MP3/6-31G*// 3-21G

459 0 533

977 0

1101

822

700 0 874 782

577 0 639 772

875 133 879

1537

1346

1167

320

178 -

164 -

2491 2733

2385 1845

1451 2345

1505

2107 2601 2710

The calculated order of relative energies is almost the same at the MP3/6-31GV/3-21G level and with MNDO for seven of the nine isomers, namely in the sequence of increasing energies, i.e., decreasing (thermodynamic) stability: cyanamide > carbodiimide > diazomethane > diazirine > nitrile imine > carbenes. Only the sequence of the two carbenes and the position of isocyanamide is different in the two methods of calculations. The calculated values for cyanamide, diazomethane and diazirine are consistent with the sequence of experimental data. The experimental energy difference between diazomethane and diazirine is, as discussed earlier in this section, still a matter of discussion, but it is likely that A/ff for diazirine is about 125 kJ mol"1 higher than that of diazomethane. This value corresponds roughly with the result of the MNDO calculation (74 kJ mol"1) and the ab initio results, provided that electron correlations are included (174 and 62 kJ mol"1). More recent calculations of the potential-energy surface for the conversion of diazirine to diazomethane by ab initio and MNDO methods have been made by Kramarenko et al. (1990). In addition to the calculation of the energies of formation of the two compounds, the energy barrier of the conversion, i.e., a measure of the inertness of diazirine, was calculated and found to be ca. 125 kJ mol-1. More recently, McAllister and Tidwell (1992) calculated the isomerization energy between diazomethane and diazirine also ab initio using the 6-31G* basis, but with the Monstergauss program (see their paper) and found diazomethane to be 20.0 kJ mol"1 more stable, i.e., a significantly smaller difference than that reported by Thomson and Glidewell. In a joint paper of Thomson with Schleyer's group (Boldyrev et al., 1992), ab initio calculations using higher levels (e.g., MP2(full)/6-31G*) also yielded smaller energy differences between diazomethane and diazirines (13.4-27.2 kJ mol"1, depending on the method).

186

5 The Structure of Aliphatic Diazo Compounds

The slightly older calculations of Chen and Tang (1988) made by the MINDO/3 SCF method with energy-gradient optimization (energy difference diazomethane-diazirine 109 kJ mol"1) are, therefore, probably outdated. This is not the case for the MC —SCF calculations with a 6-31G* basis, performed by Olivucci and Robb with their coworkers (Yamamoto et al., 1994). They calculated the energies of diazomethane (a) in Scheme 5-25), diazirine (c), bent, in-plane diazomethane (b), bent, out-of-plane diazomethane (d), and twisted, out-of-plane diazomethane (e), singlet and triplet methylene and the potential surface of this system including various excited states. Relative to the energy of the ground state of singlet methylene, diazomethane is found to be more stable by 92.8 kJ mol"1, and diazirine by 31.4 kJ mol"1. The difference of these values (61.4 kJ mol"1) corresponds very well with the respective difference found by Thomson and Glidewell (1983) using MP3/6-31GV/3-21G (see Table 5-4).

Almost exactly at the same time as the paper by Olivucchi and Robb's group (Yamamoto et al., 1994) appeared, Boch et al. (1994) published comparative calculations on the energy levels of diazomethane, (trimethylsilyl)diazomethane, nitrile imine (5.56), aminoisonitrile (5.57) and the corresponding compounds in which a hydrogen atom is replaced by a lithium atom. The energies were calculated by Hartree-Fock, M011er-Plesset 2, 3, and 4(full), CISD(FC), QCISD(T)(FC), all with 6-311 + +G(d,p) basis sets. Unfortunately, we received knowledge of that investigation only at a time when the manuscript of this book was already in press. Therefore, we can only mention the X-ray crystal structure of C-lithiated (trimethylsilyl)diazomethane, which fits well the calculations mentioned. An interesting comparison of diazomethane, diazirine (5.59), cyanamide (5.60) and aminoisonitrile (5.57,7V-isocyanamide) was conducted by Kroeker et al. (1991). They compared the experimental acidities of three of these compounds with

5.4 Isomers of Diazomethane

187

calculated deprotonation energies. For these calculations geometry optimizations of the four isomers were carried out at the Hartree-Fock level with the G-31+ G* basis set. Electron correlation was accounted for with second-order M011er-Plesset theory (MP2). The deprotonation energies were corrected for zero-point vibrational energies. The results together with experimental values for the gas phase are given in Table 5-5. The experimental gas-phase energy for diazirine corresponds to a p^Ta of 34-39 in DMSO. Table 5-5. Calculated and experimental deprotonation energies of diazomethane and three of its isomers in the gas phase (after Kroeker et al., 1991) in kJ mol"1.

MP2

exp.

Ref. for exp.

1537

1559

Liasetal., 1988; Kroeker and Kass, 1990

1694

1676

Kroeker and Kass, 1990

H2N— CN

1471

1463

Filley et al., 1987

H2N— NC

1496

-

-

H2C=N2

^N

Kroeker and Kass (1990) compared also the CH and NH acidities of diazomethane, diazirine, cyanamide and isocyanamide (see Sect. 4.4). The calculated energies correspond well with the experimental values. An important result of these calculations is the comparison of the geometries of diazirine and its anion: The remaining hydrogen bends further away from the plane of the ring (74.1 ° in the anion instead of 59.1 ° in diazirine), and the CN bond lengths increase (152 pm instead of 145 pm). These changes in geometry tend to localize the negative charge on the C-atom and minimize the cyclic 47i-electron interaction. As it is known that in the flash thermolysis of tetrazole (5.80) in the vapor, cyanamide, diazomethane, and dinitrogen are formed, Guimon et al. (1989) calculated with ab initio (3-21G*) and with MNDO methods the potential energy surface including the compounds mentioned and diazirine (5.59), carbodiimide (5.77), isodiazirine (5.78), and the nitrene 5.82. Tetrazole is calculated slightly more stable than its isomer 5.81. An interesting subject is the influence of substituents on the relative stability of the corresponding diazomethane and diazirine derivatives, because there is a qualitative indication that difluorodiazirine is more stable than difluorodiazomethane.

H \

/

C —N

H

V> 5.80

s

H \

C= N

\>5.81

188

5 The Structure of Aliphatic Diazo Compounds

\C=N /H X

:N 5.82

Difluorodiazomethane (CF2N2) is not yet known experimentally, but difluorodiazirine has been known for more than a quarter of a century by the work of Mitsch and his coworkers (Bjork et al., 1965; Mitsch, 1966). The geometry is significantly different from that of diazirine; the NN bond is 6.5 pm shorter, the CN bond is 5.6 pm longer, and the N-C-N angle is larger (53.95° compared with 48.9° in diazirine; Hencher and Bauer, 1967). Difluorocyanamide (F2NCN) is also a known compound. Its structure was verified in a microwave evaluation by Lee et al. (1972). Whereas cyanamide is almost planar at the amino N-atom, F2NCN is markedly pyramidal with a bond-angle sum at N of only 313.6°. Glidewell et al. (1987) were the first to attempt to solve that problem by theory (by ab initio SCF on the HF/3-21G level and by MNDO). Their calculations gave the result that difluorodiazomethane should be more stable than the known difluorodiazirine. As this conclusion is doubtful, the groups of Thomson and Schleyer as well as McAllister and Tidwell investigated it again by the methods they had already applied for the unsubstituted isomers. In both papers, energy values are reported indicating that difluorodiazirine is more stable by 107-122 kJ mol'1 (Boldyrev et al., 1992) and 51.9 kJ mor1 (McAllister and Tidwell, 1992). In addition, in both communications additional substituted diazomethanes and corresponding diazirines were investigated theoretically (Boldyrev et al.: monofluoro derivatives; McAllister and Tidwell: 19 monosubstituted compounds). The latter two authors found that the correlation with substituent electronegativities on the basis of an isodesmic reaction for monosubstituted diazomethanes (see Sect. 5.3, Scheme 5-8) is not present for the corresponding substituted diazirines. Results for the other isomers of difluorodiazomethane are not directly interesting for the subject of this book. More relevant is the replacement of carbon for silicon in the series of isomers of diazomethane. For the two most important sila-isomers for discussion here, diazosilane (H2Si=N2) and siladiazirine, no experimental evidence appears to have been published, but silacarbodiimide (HN = Si = NH) is known (Ando et al., 1981 a), although no information on structural parameters is available. Thomson and GlidewelPs calculations (1983) give very different results for silacarbodiimide with ab initio/3-21G and MNDO calculations: at the 3-21G level the N-Si-N angle is predicted to be 180°, with MNDO 118°; the SiN bond is calculated to be short with SCF (155 pm), but long with MNDO (163 pm). Diazosilane is predicted to be quite different from diazomethane. The Si —N —N fragment is calculated to be essentially linear, but the angles H —Si —N and H —Si —H are postulated to be 85° and 95°, respectively. The typical delocalization of orbitals in diazomethane over the C-N-N fragment does not result from calculations of H2SiN2. There the HOMO is largely localized on the Si atom. A detailed examination of the wave function shows little bonding between the Si- and

5.4 Isomers of Diazomethane

189

N(a) atoms. If that bond is stretched to 400 pm, the energy is increased by only about 25 kJ mol"1. The authors conclude from this result that diazosilane is a loose complex of distorted H2Si and N2. The structure of sila-diazirine is not substantially different from that of the carbon compound. However, the charges on the atoms are quite different, the silicon bearing a positive charge of 0.87 compared with the carbon charge of —0.23. As a consequence, the N-atoms are calculated to carry a significant negative charge.

6 Reactions of Aliphatic Diazo and Diazonium Compounds not Involving Initial Dediazoniation

6.1 Azo Coupling Reactions of Aliphatic Diazonium Ions and Related Processes In the 1930's, investigations on the diazotization of aromatic amines and the reactions of nitrous acid with aliphatic amines made it likely that in the latter processes alkanediazonium ions are formed as intermediates, that the deamination of aliphatic amines belongs mechanistically to the class of nucleophilic aliphatic substitution (see Chapt. 7), and that the formation of the alkanediazonium ion is followed by a very fast dediazoniation. These considerations led to the hypothesis that alkanediazonium ions may be trapped by a rapid addition, e. g., in an azo coupling reaction. In a classical investigation, Bartlett and Knox (1939) showed that l-chloro-7,7-dimethylbicyclo[2.2.1]heptane (6.1, R = CH3, X=C1) solvolyzes very slowly, while deamination of the respective amine (6.1, R=CH 3 , X=NH 2 ) proceeds easily. This work started a significant activity on nucleophilic substitution of bridgeheadsubstituted alicyclic compounds (for early reviews, see Bartlett, 1951, and Applequist and Roberts, 1954). They led to the idea that diazonium ions formed in deaminations of bridgehead amines may be trapped as azo compounds. Curtin et al. (1962) successfully used 9-aminotriptycene-l,4-dione in dichloromethane at — 78 °C in the presence of 2-naphthol (6-1; yield: 50%). Later, Scherer and Lunt (1966) could demonstrate that azo coupling of the diazonium salt derived from the extremely electrophilic bridgehead polychlorinated homocubaneamine 6.2 took place with 2-naphthol and even with coupling components of relatively low reactivity (methoxyand 1,3,5-trimethylbenzene)*. On the other hand, trapping by azo coupling was not

* For the formation of a homocubyldiazonium ion in the thermolysis of the corresponding homocubyl-W-nitrosoacetamide see the work of Rtichardt's group (Mergelsberg et al., 1983). Trapping experiments were not performed, however. Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

192

6 Reactions of Aliphatic Diazo and Diazonium Compounds .R

(6 1)

'

observed in deamination of bicyclo[2.2.1]heptane-l-amine (6.1, R=H, X=NH 2 ; Kirmse and Seipp, 1974; Kirmse et al., 1979). Azo coupling reactions are frequently observed in diazo transfer processes in which 4-toluenesulfonyl and other azides react with highly reactive methylene compounds, e.g., with dicarbonyl compounds (see Sect. 2.6, Schemes 2-56, 2-59, and 2-63). Such reactions were not, however, investigated mechanistically. Thus, although it is likely that alkanediazonium ions are intermediates, there is no direct evidence for their intermediacy. The first azo coupling products of simple (i. e., not bridgehead) compounds were detected by Nesnow and Shapiro (1969), when they allowed l,2-dihydro-6-hydroxypyridin-2-one (6.3) to react with a large excess of diazomethane (1:100) in ether. They isolated l,2,3,6-tetrahydro-l-methyl-2,6-dioxopyridine-3-one methylhydrazone (6.4) in addition to the expected products of N- and 0-methylation (6-2). An analogous result was reported by Testaferri et al. (1975) for the reaction of diazoethane with the thieno[3,2-6]thiophene derivative 6.5, where Oll-ethylation and azo coupling in 3-position are observed. Nesnow and Shapiro and Testaferri et al. assume that the diazoalkanes are first protonated, in the case of l,2-dihydro-6-hydroxypyridin-2-one by the proton of the hydroxy group, with the thienothiophene derivative due to the tautomerism 6.5 ^ 6.6, i.e., by one of the protons of the methylene groups in 3- and 5-position of 6.5 and 6.6, and the formation of an intermediate ion pair of type 6.7.

6.1 Azo Coupling Reactions of Aliphatic Diazonium Ions and Related Processes

6.4(14%)

,fX)^o N S^^V

6.5

3

193

(2%)

_

<^}=o x g^^/ 6 6

-

Although the thienothiophene derivative is a rather special case of an azo coupling component *, the explanation of Testaferri et al. with the help of the ion pair 6.7 seems to have general significance (although the authors do not mention it): even if dediazoniation of the ethanediazonium ion in the ion pair would be extremely fast, the azo coupling may compete within the ion pair. It is known from the work of Bourne et al. (1988, 1992) and others that azo coupling reactions of arenediazonium ions can be diffusion-controlled (see review, Zollinger, 1994, Sect. 12.9). There is no obvious reason why this should not also be the case for alkanediazonium ions. There are few known cases of azo coupling with classical aromatic coupling components, e.g., diazomethane, ethyl diazoacetate, and diazoketones with benzene1,3,5-triol (Severin, 1958) and dicyanodiazomethane with 7V,7V-dimethylaniline (Ciganek, 1965 a). Occasionally, competition between 1,3-dipolar cycloaddition and azo coupling of diazoalkanes has been observed. Three cases of reactions with enamines have been

* It seems that the thienothiophene 6.5 has not been tested as such in azo coupling with aromatic diazonium salts.

194

6 Reactions of Aliphatic Diazo and Diazonium Compounds

reported by Schollkopf et al. (1975) and Huisgen et al. (1979 a, 1979 b), but not evaluated further in more detail. As discussed intensively in the book on aromatic diazo compounds (Zollinger, 1994, Chapt. 6), azo coupling takes place not only with C-nucleophiles, but also occurs at nucleophilic N-, O-, S-, and P-atoms. Kirmse and his coworkers devoted considerable effort to investigate short-lived alkanediazonium ions by their reactivity in AT-azo coupling, using lithium azide as nucleophile. Aromatic and aliphatic diazonium ions react with azide ions not only by addition and dediazoniation, leading to aryl and alkyl azides, but also via pentazoles, which later lose N2 (see reviews: Huisgen, 1984, p. 152; Zollinger, 1994, Sect. 6.4). The two pathways can be differentiated by a- or /?-15N labeling. Kirmse et al. (1973) made the interesting observation with this technique that cyclopropanediazonium ions react with azide ions in the manner of an azo coupling reaction, whereas butane-1-diazonium ions do not. Bicyclo[2.2.1]heptane-l-diazonium ions react neither by azo coupling, nor via pentazoles, but the complete loss of 15N (if a labeled diazonium ion and unlabeled azide ion are used) is consistent only with the addition of N3~ to the carbocation, i.e., after the dediazoniation (Kirmse et al., 1979). Kirmse et al. (1973) found, however, in the azido-de-diazoniation of the 15N-cyclopropanediazonium ion that here the analogous result (no 15N label in the cyclopropylazide formed) is the result of a base-catalyzed reaction. This indicates that here the diazonium ion is first deprotonated to diazocyclopropane. This intermediate loses N2 with formation of the cyclopropylidene carbene, which then reacts with the azide ion and is finally protonated to give cyclopropyl azide. The investigations of Kirmse's group (1973) also include the reaction of azide ions with some alkenediazonium ions. Formation of alkenylidenecarbenes (RR'C = C:) is known from other reactions with alkenediazonium ions (e.g., Patrick et al., 1972). Product ratios and the results of 15N(a)- and 15N(/?)-labeling indicate that alkenylidenecarbenes are formed in the reaction of azide ions with 2,2-dialkyl- and 2-cycloalkylethene-l-diazonium ions, but not with 3-methylbut-2-enediazonium ions (as expected). It is rather curious that P-coupling of diazoalkanes had been found at a very early date. Staudinger and Meyer (1919) discovered that such reactions take place with trialkyl- and triarylphosphines. As shown later by Wittig and Haag (1955), even diazomethane reacts with phosphines. These couplings proceed so readily, because the P-azo product (6.8) is stabilized by acceptance of 7i-electrons into the empty d orbital of the P-atom *. Azo coupling reactions with stable aliphatic diazonium ions (see Sect. 2.1) have not been investigated, as far as we are aware. N-P(Ar)3

^

N=P(Ar)3 R2C = N

R2C —N 6.8

* For a recent investigation with 4-ethyl bicyclic phosphite, see Pei and Xu (1993).

6.2 Introduction to 1,3-Dipolar Cycloadditions

195

All investigations on C-, N- and P-azo coupling reactions of aliphatic diazonium ions provide evidence that aliphatic diazonium ions indeed exist, albeit only as shortlived intermediates. Activity in this field, therefore, drastically decreased during the 1980's. We should emphasize that the investigations conducted previously are not sufficient for a general understanding of the structural and energetic requirements for obtaining azo coupling products from precursors of aliphatic diazonium ions. Azo coupling reactions of diazoalkanes have been reviewed by Hegarty (1978, p. 214), and by Szele and Zollinger (1983, p. 3).

6.2 Introduction to 1,3-Dipolar Cycloadditions In the historical introduction to this volume (Sect. 1.1), it was mentioned that Buchner studied reactions of ethyl diazoacetate with ethenedicarboxylic acid in 1888. In the following year, he discovered pyrazole, obtained from methyl diazoacetate and dimethyl acetylenedicarboxylate followed by thermolysis. Finally, in 1893 Buchner et al. synthesized 4,5-dihydro-l//-pyrazole (2-pyrazoline) from methyl diazoacetate and methyl acrylate. Von Pechmann, the discoverer of diazomethane, performed analogous reactions of fumarates and maleates (von Pechmann, 1894, von Pechmann and Burkard, 1890)*. Two other classes of compounds and their five-membered ring derivatives with alkenes and alkynes were found in the 1890's, namely azomethine oxides

=]^J( j, or nitrones** by Beckmann in 1890, and azides by Michael in 1893. Two additional classes with corresponding reactions of five-membered ring compounds only were discovered in the first half of the 20th century, namely 1,2,3- (later also 1,2,4-) trioxolane ring formation of ozone by Harries (1905) and isoxazole syntheses with nitrile oxides (-C = N = O) by Quilico and Fusco (1937). The first attempt at a general concept for the formation of five-membered rings with compounds containing a central N-atom, i. e. , with four of the five groups of reagents above, was undertaken by Smith in 1938. Smith also included azoxy compounds and Staudinger's addition products of 7V-arylazomethine oxides to diphenyl ketene. Staudinger and Miescher (1919) assumed these compounds were azomethine ylides. Yet, Hassall and Lippman (1953) showed that this assumption was not correct. In the late 1950's, Huisgen developed the general concept of 1,3-dipolar Cycloadditions — again at the University of Munich, where Buchner and von Pechmann had found the first cyclizations of this type 70 years earlier. Since the 1950's, it has been known that the dominant character of diazomethane is that of a carbanion base (see Sect. 4.4). The addition of a,/?-unsaturated com* In part, Buchner's and von Pechmann's original structures of the products were not correct, as structural theory at the end of the 19th century was still in its infancy. Original representations of these and other early authors can be found in Huisgen's review (1984). ** The name nitrone reflects a misleading analogy with ketones (Pfeiffer, 1916).

196

6 Reactions of Aliphatic Diazo and Diazonium Compounds

pounds such as acrylates and the subsequent cyclization was formulated by Eistert (1941) and Young et al. (1944) as a two-step reaction (6-4). This mechanism is, however, difficult to apply to the fast cycloaddition of diazoacetates (Alder et al., 1931) and 3-diazobutane-2-one (Diels and Konig, 1938) with alkenes of the bicyclo[2.2.1]heptene type, because alkene C-atoms without electron-withdrawing substituents show no electrophilic character. The reverse sequence of steps in (6-4), i. e., first an additon of N at the central C-atom of the acrylate, would also be unusual, as the N (/?)-atom of diazoalkanes is only a weak electrophilic center. Fleischmann (in Huisgen's group, 1958) showed that, in such cyclization reactions, the rate of reaction of diazomethane with bicyclic alkenes relative to that of /?-diazo ketones and 2-diazo-l,3-diketones is higer by a factor of 104-105.

COOCH3

This and other evidence led Huisgen to propose (1960, 1961) a concerted mechanism for these reactions. In his early publications, he emphasized already that this mechanism is not only typical for diazoalkane cycloadditions, but also for those of the other compounds mentioned before in this section, and he also showed that the dipolar character of these reagents is most important. We will concentrate on general principles of all 1,3-dipolar cycloadditions in the rest of this section. Mechanistic aspects and the theoretical basis will be discussed in detail in the following section, with preference for diazo dipoles. 1,3-dipolar cycloadditions are reactions of a 1,3-dipole (a=b + — c~) with a doubleor triple-bond system, the dipolarophile (d=e; Huisgen, 1963a, Scheme 6-5*). It is called dienophile when used in cycloadditions with dienes (Diels —Adler reactions). The three atoms of the 1,3-dipole are either C, N, or O **. The charge of the onium center b is compensated by the negative charge that is distributed over the atoms a and c, and the ambivalence of the 1,3-dipoles is illustrated by the sextet structures (Scheme 6-6).

1,3-Dipole

Dipolarophile

nd=e c'

" \a—e ri /

(6 5)

-

* The dashed line between d and e indicates the cycloaddition with a triple-bond dipolarophile. d and e may be, besides alkenes and alkynes, functional groups CEEE X or X^ Y, where X and Y are N, O, S, Se, or P (see Sect. 6.5). ** In some cases, b may be an atom of the third-period elements P or S, respectively.

6.2 Introduction to 1,3-Dipolar Cycloadditions

197

Octet structures

(6-6)

Sextet structures + /£\

- **

*~ ~a

'^c+

Experience has shown, however, that simple resonance considerations are not satisfactory for predicting and understanding regioselectivity in reactions with unsymmetric dipolarophiles. A 1,3-dipole as shown in Schemes 6-5 and 6-6 corresponds to a system with three parallel atomic p-orbitals, i.e., to an allyl anion, but without net charge. It is, therefore, called an allyl-type 1,3-dipole. The system may contain, however, an additional 7i-bond in the plane perpendicular to the allyl anion type molecular oribtal, and then belongs to the propargyl — allenyl type. Normally, 1,3-dipoles of this type are linear, whereas those of the allyl type are bent. The term "1,3" relates to the reactivity in these positions, not to formal charges. A series of theoretical studies (e. g., by Hiberty and Leforestier, 1978; Yamaguchi et al., 1980; see review of Houk and Yamaguchi, 1984) clearly show, however, that some of these 1,3-dipoles have considerable biradical character (e.g., O3 53% and CH2N2 28% in ab initio calculations at the 4-31G level). We will return to biradicals in the mechanistic discussion of Sect. 6.3. Permutation to second-period elements yields six 1,3-dipoles of the propargyl — allenyl type and twelve of the allyl type (Table 6-1)*. In 1960, cycloadditions of only six of these 18 classes had been described in the lieterature (see Table 6-1). Four other 1,3-dipoles were known, but not yet used for cycloadditions. The last column of the table demonstrates clearly how many new classes of cycloaddition reactions were discovered in the 1960's and 1970's after Huisgen had identified the general concept behind all these cyclizations. These data are the most convincing evidence for our claim that 1,3-dipolar cycloadditions are the most important achievement for organic synthesis that was based on preceding mechanistic considerations, as described in Huisgen's Schemes 6-5 and 6-6. An interesting addition to Huisgen's classical list of 18 1,3-dipoles (Table 6-1) are the cyclopropenone ketals, e. g., 6.9. Although known for more than two decades (Baucom and Butler, 1972), their mechanistic behavior and synthetic potential (e.g., for a synthesis of colchicine) was realized only by Boger and Brotherton-Pleiss (review: 1990). Cyclopropenone ketals do not, however, belong to the scope of this volume. 1,3-Dipolar additions of carbonylcarbenes are closer to diazo chemistry, because carbonylcarbenes are formed from a-diazo ketones. Carbonylcarbenes are

* In those classes of 1,3-dipoles where only third-period element compounds are used or known, it is mentioned (footnotes b and d: S instead of O).

Table 6-1. Classification of 1,3-dipoles consisting of carbon, nitrogen, and oxygen centers (after Huisgen, 1963 a, 1994; mesomeric formulae show formal charges only, but not electron pairs). First use for cycloaddition

Propargyl-Allenyl Type Nitrilium Betaines -«N-<

—

-C=N=<

+

-

-

+

+

-

-

+

Nitrile Ylides

Huisgen et al., 1962 c

Nitrile Imines

Huisgen et al., 1967

Nitrile Oxides

Quilico and Fusco, 1937

Diazoalkanes

Buchner, 1888

Azides

Michael, 1893

Nitrous Oxide

Buckley and Levy, 1951

Azomethine Ylides

Huisgen et al., 1963

Diazonium Betaines N=N-C^ •* +

^

N=N=C<

-

N=N— O

+

*<

^

N=N=O

Allyl Type Nitrogen Function as Middle Center >=N~< -

^ /C~N=<

Azomethine Imines a) Huisgen and Eckell, 1960; sydnones: Vasil'eva et al., 1961

>=N-N^ — ^

>-W

'

*" ' \~ Nitrones

~\

"*

\ \

+ -

~l

\

"*

-+

*"

Azimines

Gait et al., 1972

Azoxy Compounds

Challand et al., 1973

Nitro Compounds

Leitich, 1976

C^

Carbonyl Ylides

Linn and Benson, 1965

N^

Carbonyl Imines

Burgess and Penton, 1974 )

O

Carbonyl Oxides

N^

Nitrosimines

Criegee (1975), Sander (1990), Bunnelle(1991)c) -

O

Nitrosoxides

Barton and Robson, 1974 )

0

Ozone

Harries, 1905

~l~

1

O=N-6 i

Beckmann, 1890

\

1

•<

>•

O— N=O i

Oxygen Atom as Middle Center

6.2 Introduction to 1,3-Dipolar Cycloadditions

199

a

) The class of azomethine imines includes the sydnones, see Sect. 6.3. ) Thiocarbonylimine^C=S— N^. c ) Carbonyl oxides are intermediates in ozonizations (the references are reviews; see also Scheme 9-36 in Section 9.4).

b

d

) ThiosulfinylamineXxN=S-S.

1,3-dipoles that react with dipolarophiles such as ethenes, ethynes, etc., as shown in Scheme 6-8 (Huisgen et al., 1964a, 1964b). In contrast to other 1,3-dipolar cycloadditions, these reactions are not stereospecific. Diazo ketones that are not as electrophilic as 2,3,4,5-tetrachloro-6-diazocyclohexa-2,4-dien-l-one give 1,3-dipolar cycloaddition products only in very low yield. Photolysis yields only traces (Huisgen et al., 1964a). Ketocarbenoids are important for cyclopropanations (see Sect. 8.6).

75°C

(6-7)

6.9

200

6 Reactions of Aliphatic Diazo and Diazonium Compounds

Huisgen's general concept was not only fruitful for synthetic applications after 1960, but also for thorough evaluations of the mechanism of 1,3-dipolar cycloadditions, carried out simultaneously. Within three years, Huisgen came to quite remarkable conclusions (1963 a, b) with respect to stereochemistry and orbital control of these reactions: they fitted very well to the principle of conservation of orbital symmetry (Hoffmann and Woodward, 1965). We will discuss this and subsequent mechanistic work on 1,3-dipolar cycloadditions in Sect. 6.3. There are numerous reviews on 1,3-dipolar cycloadditions. We will mention only those published since 1984, first of all the two-volume handbook, edited by Padwa (1984), then reviews by Drygina and Garnovskii (1986), Samuilov and Konovalov (1986), Huisgen (1988), Tsuge et al. (1989), Carruthers (1990), Padwa and Schoffstall (1990), Padwa (1991 a, 1991 b), Wade (1991) and Rauk (1994)*. This extensive literature clearly demonstrates the current interest in these cyclization reactions. Occasionally, the term 1,3-dipolar cycloaddition is also used for the reaction of diazoalkanes with transition metal complexes, e. g., (6-9), investigated by McCrindle and McAlees (1993). This is not, however, a 1,3-dipolar cycloaddition as coined by Huisgen. This term should not, therefore, be used for reactions that involve a dipolar reagent, but only in a cycloaddition with a dipolarophile, as shown in Huisgen's mechanism (Schemes 6-5 and 6-6). They may be called [3 + 1] dipolar cycloadditions, however, in order to underline the difference to the [3 + 2] reactions. H R

~Cx\ S

N

!l

N "fc

N

ci' vci

P

17

H-PlS

1

Cl

-P = P(C6H5)2—CH—CH—P(C6H5)2 CH3

6.3 Mechanism of 1,3-Dipolar Cycloadditions On the basis of the discussion in the preceding section (Schemes 6-5 and 6-6, Table 6-1) one easily realizes that in 1,3-dipolar cycloadditions six Ti-electrons are involved, four provided by the 1,3-dipole and two by the dipolarophile, as described See the additional reviews discussing diazoalkane cycloadditions only, in Sect. 6.5.

6.3 Mechanism of 1,3-Dipolar Cycloadditions

201

by the notation [7i4s + 7t2s]. A cyclic transition state with six rc-electrons leads every organic chemist to consider the idea of aromatic character and, therefore, of a planar arrangement of all five atoms involved. The mesomeric structures of the 1,3-dipoles shown in Table 6-1 indicate, however, that planarity is unlikely in all those of the 18 classes in which one or both of the terminal atoms a and c bear two substituents, e. g., the C-atom in nitrones, in 2-diazopropane, in azomethine ylides, and imines, etc. These substituents do not allow approach of the dipolarophilic atom d to the C-atom a, except after a 90° rotation around the a=b double bond. Such rotational barriers have been measured; e.g., in nitrones they are 140 ± 6 kJ mol"1 (Dobashi et al., 1973). Activation enthalpies A//* of nitrone cycloadditions are, however, only 66-76 kJ mol"1 (Huisgen et al., 1969). Activation barriers for many cycloadditions with various 1,3-dipoles and dienophiles are even lower (see the compilation of Huisgen, 1984, Tables 12-14, e.g., diazomethane + ethyl acrylate, one of the fastest cycloadditions, k = 2.16 M"1 s"1; A//* = 31 kJ mol"1). The answer to this dilemma was provided by Huisgen et al. (1962 a, 1962 b) by the cycloaddition reaction of C-methyl-7V-phenylsydnone (6.10) with styrene, which yields, via the bicyclic intermediate 6.11 and elimination of CO2, 4,5-dihydro5-methyl-l,3-diphenyl-l//-pyrazole (6.12). As mentioned briefly in Section 6.2 (Table 6-1, footnote a), sydnones are cyclic azomethine imines. As Huisgen (1968) demonstrated later, sydnone and azomethine imine cycloadditions are kinetically very similar with respect to solvent effects and in the sequence of reactivity with a series of 11 dipolarophiles.

6.10

6.11 I (6-10)

6.12

The intermediate 6.11 cannot be planar. Interaction of the ethene n molecular orbital of styrene can take place with the MO of the sydnone 1,3-dipole only if the o-bond systems of these reagents are located in two approximately parallel planes. Therefore, Huisgen (1963b) suggested the two-plane orientation complex 6.13 for the transition state of this cycloaddition. This transition state is feasible not only for

202

6 Reactions of Aliphatic Diazo and Diazonium Compounds

6.13

a sydnone, but also for all other 1,3-dipoles. The four overlapping p orbitals are converted into sp3 orbitals and form the two new o bonds. The central N-atom is raised and pyramidalized. If one is interested in the development of scientific ideas, the basic principles of this mechanism and, particularly the postulate of the two-plane orientation complex 6.13 are remarkable, because they were published two years before Hoffmann and Woodward established the principle of the conservation of orbital symmetry for cyclization reactions in 1965. This principle also includes the postulate of two-plane orientation complexes, but primarily for Diels-Alder reactions, which are also [;c4s + 7t2s] cyclizations. Inclusion of the Huisgen mechanism (6-10) into the framework of the Woodward — Hoffmann rules was accomplished in an annex to a paper of Huisgen's group published in 1967 (Eckell et al.) and in the review of Woodward and Hoffmann (1969)*. Yet even before that evaluation, Fukui (1966) demonstrated that this frontier orbitals overlap principle readily allows prediction of the favored mechanism. This principle is based on a preference for those pathways that show maximum overlap of the highest occupied orbital (HOMO) of one reagent with the lowest unoccupied orbital (LUMO) of the other reagent**. The two reagents combine suprafacially. Although the first MO symmetry correlations for 1,3-dipolar cycloadditions (Eckell et al., 1967; Woodward and Hoffmann, 1969) were made for the electronic prototype allyl anion + ethene only, it was shown that heteroatoms and substituents destroy the molecular symmetry, but will allow application of selection rules, as orbital symmetry is normally not changed. Inclusion of 1,3-dipolar cycloaddition into the framework of orbital symmetry control made it clear that not only cyclizations in which (4 + 2) n electrons are involved in the bonding process, but also analogous reactions with (4q + 2) n electrons (q > 1) follow the same principles. Not many such cases are known. An example is the addition of diazocyclopentadiene

* Huisgen's mechanism was also discussed on the basis of the principle of orbital correspondence analysis in maximum symmetry (OCAMS) by Halevi (1992, p. 168). ** For further reviews of the frontier orbital approach, see Fukui (1970, 1971, 1982) and Fleming (1976).

6.3 Mechanism of 1,3-Dipolar Cycloadditions

203

to dimethyl ethynedicarboxylate (6-11) in which dimethyl-2//-cyclopenta[c]pyridazine-3,4-dicarboxylate (6.14) was found to be the main product (Cram and Partos, 1963). This process is a [7i8s + 7i2s] cycloaddition, i.e., q = 2.

(6-11)

In this section we discuss first experimental data that are helpful for providing an answer to the question whether in 1,3-dipolar cycloadditions the two o bonds are formed in a concerted process, i. e., with one transition state (as shown in 6.13), or stepwise via a zwitterionic or biradical intermediate. We include investigations with dipole reagents other than diazo compounds, when appropriate or even necessary for understanding mechanistic problems in cyclization reactions of diazoalkanes. In the second review (1963 b) of Huisgen, the ambiguity "concerted or zwitterionic intermediate" remained an open question. Woodward and Hoffmann's selection rules define the conditions under which concerted processes are allowed, but they do not forbid a two-step pathway *. The sydnone 6.10 in cycloaddition (6-10) belongs to the allyl-type 1,3-dipoles, and is, therefore, bent, as shown in the transition state 6.13. The propargyl — allenyl type 1,3-dipoles are, however, not bent at the central atom. This is, therefore, the case for diazoalkanes, i.e., the 1,3-dipoles of central interest for this book. Is it indeed possible that transition states similar to 6.13 can be formed at all in 1,3-dipolar cycloaddition of diazomethane? Bastide and Henri-Rousseau (1972) calculated by CNDO/2 that bending diazomethane to an angle of 109° at the N(a)-atom requires 92 kJ mol"1! This result seems to exclude a transition state of the type discussed for the sydnone reaction. Yet, analogous calculations, conducted by Houk et al. shortly afterwards (1973 a), have shown in addition that bending at the N(a)-atom does not change the HOMO-LUMO energy differences significantly. Fukui's group (Minato et al., 1974) found by semiempirical SCF calculations (including configuration interaction) of diazomethane reactions that the cyclization was concerted (no intermediate), but that the new bonds are not formed synchronously. The problem of bending diazomethane for the cycloaddition transition state was basically answered by Leroy and Sana's investigations (1975, 1976 a). Using ab initio SCF calculations at the STO-3G level, they evaluated some 150 points on the hypersurface of diazomethane, ethene, and the primary cyclization product 1-pyrazoline. The essential results are shown in Scheme 6-12. There is no second transition state,

* This was shown for the Diels-Alder cyclization of (Z)- and (£>l,2-dichloro-l,2-difluoroethene in the classical investigation of Bartlett and Mallet (1976).

204

6 Reactions of Aliphatic Diazo and Diazonium Compounds

i. e. , there is no intermediate * Most important is the geometry of the two reagents in the transition state: bond angles are changed relatively little relative to those in the reagents, bond lengths are still the same, but change strongly after the transition state**. All these data are consistent with a very early transition state, i. e., an energy maximum without very large geometry changes on the way to the transition state ***. We will return to the bending of diazoalkanes in the transition state in Section 6.4, where we will discuss an improved perturbation program of Sustmann and Sicking (1987 a, 1987 c). 180°

130pm 114pm 148pm Nx124pm <>N 112

7

(6-12)

-

134pm Reagents

Transition state

Product

Leroy and Sana's main conclusion explains some kinetic data obtained by Huisgen's group in cycloadditions of benzonitrile oxide, diphenylnitrile imine, diazomethane and diphenyldiazomethane with a series of ethyne- and ethene-based dipolarophiles (6-13 and 6-14). In the reactions with diphenylnitrile imine and benzonitrile oxide (Bast et al., 1973) the cyclizations with the ethene compounds are 2-10 times faster than those with the derivatives of ethyne. The analogous reactions with the two diazoalkanes (Fisera et al., 1978) show a smaller difference between the two dipolarophiles. The results of the reactions with benzonitrile oxide and diphenylnitrile imine (6-13) cannot be understood on simple arguments of aromaticity, which predict that reactions with ethyne-type dipolarophiles should proceed faster, as an energetically more favorable transition state is formed. This is not the case with the ethene reagent. The conclusion from theory, however, indicates that, with both dipolarophiles, the transition state is reached with a structure in which aromaticity is not yet built up. The experiments with the diazoalkanes (6-14) lead to the same conclusion. Here, the primary products with both dipolarophiles are not aromatic. In the combination diazomethane + ethyne reagent, the primary nonaromatic pro-

* This conclusion is consistent with ab initio calculations at the molecular orbital level (Komornicki et al., 1980), but in contrast to analogous work including extensive electron correlation (Hiberty et al., 1983). See also our remarks in this section after the discussion of the reaction in (6-17). ** Today, i.e., almost two decades after Leroy and Sana's investigation, it seems that it would be worthwhile to reinvestigate that hypersurface with more sophisticated methods available now. Is the C-N-N angle really only 150°? *** Leroy and Sana (1976b), and Leroy et al. (1976, 1978) also investigated other types of 1,3-dipoles in addition to diazomethane. We do not review them here because of space reasons.

6.3 Mechanism of 1,3-Dipolar Cycloadditions

r6 w 5^X' J\ U

M

\

R

/=<

X

i

+

RC^CR'

<< R/

+

-

C6H5—C = N-X

205

PM ^

+ RCH=CHR'

*-

O6H5-^X

H

-

X = N-C6H5

\

/

(6-13)*

(6-14)* HlR"

duct, a 3//-pyrazole, rearranges by a C,N(/?)-proton shift into the aromatic pyrazole, but this is, of course, a secondary reaction that has no influence on the cycloaddition. Nevertheless, cycloadditions are significantly slower if the aromaticity of either a 1,3-dipole or a dipolarophile is lost in the reaction. A typical example is the comparison of the two dipolarophiles cyclopentadiene and furan. Caramella et al. (1976) found that the rate of reaction of benzonitrile oxide with the nonaromatic cyclopentadiene is 930 times faster than that with the aromatic furan. The rate ratio indicates a 15-25% loss of aromaticity, a result that is consistent with an early transition state. The examples given above on the influence of aromaticity in the reagents and its missing influence if the products are aromatic compounds were understandable on a relatively simple basis. More general structure - reactivity relationships were, however, not yet found in the 1960's in spite of a large body of experimental data. This situation changed relatively quickly when the principle of conservation of orbital symmetry was applied, as mentioned earlier in this section. In a semiquantitative way it can be depicted as shown in the MO symmetry correlation diagram of Figure 6-1**. The schematic energy correlation in this figure shows the electron flow in the reaction, namely from the highest occupied orbital of the 1,3-dipole (i|/2) to the lowest unoccupied orbital of the dipolarophile (XI/B), and from the HOMO of the dipolarophile (\|/A) to the LUMO of the 1,3-dipole (11/3). The two terms A^ and A£"n correspond to the energies of the two HOMO —LUMO interactions in the transition state. Their sum is, therefore, a measure of the reactivity. The energy levels of all MO's of both reagents are, of course, dependent on their structure. The reactivity of the case depicted in Figure 6-1 is influenced more by the HOMO(dipole) — LUMO(dipolarophile) energy difference A^n than by the interaction HOMO(dipolarophile) — LUMO(dipole), i.e., A£ I II >A£' I . The reverse case > A.E'n) and extremes like A.E'n > A£"j« 0 are also feasible. This clearly ex-

* R' R" = COOAlk, w-C4H9, C6H5, H and other substituents. ** As mentioned above, the first such diagram for a dipolar cycloaddition was published by Eckell et al. (1967). Figure 6-1 is based on a more recent representation of Huisgen (1988, Scheme 13).

206

6 Reactions of Aliphatic Diazo and Diazonium Compounds

1,3-Dipole

(LUMO)

v¥3

/1 ^ -D^

oOo a—b—c -

(HOMO)

¥2

Dipolarophile

od-e o

*B

{LUMO)

a-b-c

0 0 oO , Oa—b—c --

0"0

Fig. 6-1. MO symmetry correlation diagram for 1,3-dipolar cycloadditions.

plains that simple structure — reactivity relationships (e. g., Hammett relations) are not likely to be found, except for the two extreme cases. The theoretical background for the calculation of A£j and A£"n and its application to the structure — reactivity correlations is due to Sustmann (Sustmann, 1971; Sustmann and Trill, 1972; review: 1974, and other papers mentioned there) and Houk's group (Houk et al., 1973a, 1973b, 1980; reviews: Houk, 1975; Houk and Yamaguchi, 1984; and Rauk, 1994)*. These calculations are based on the determination of the HOMO and LUMO energy levels \|/2, 11/3, XJ/A> and \|/B of the 1,3-dipole and the dipolarophile (Fig. 6-1) including perturbation, i.e., interaction forces (PMO). The appropriate HOMO — LUMO coefficients allow prediction of which of the two newly forming a bonds will be the strongest in the transition state. Such knowledge is useful not only for structure — reactivity relationships, but also for regiospecificity, which we will discuss in Section 6.4. The frontier orbital - second-order perturbation concept (Sustmann and Trill, 1972) led to an equation for the energy gain bJZ resulting from formation of the two new o bonds in the cycloaddition, shown in a simplified form in (6-15). The \\f terms, AJ?!, and A^n correspond to those in Figure 6-1. Az and An include the overlap between the occupied and unoccupied orbitals and the resonance integral. AE = AE, + AEN = '

"

—

¥A - Vs

+

"

¥2 - %

* An elementary description was published by Huisgen (1984, pp. 110-120).

(6-15)

6.3 Mechanism of 1,3-Dipolar Cycloadditions

207

The result of these calculations allows recognition of the dominant bond formation and, as a consequence, the interpretation of substituent effects. As mentioned above, there are, on a semiquantitative basis, three types of combinations between A£n and AJEj (Fig. 6-1); A£n > A^; AEn « ABj; A£n < ABj. These combinations are called types I, II and III by Sustmann (1971), or HO-controlled, HO,LU-controlled, and LU-controlled by Houk et al. (1973 b)*. In type-I reactions, the HOMO(dipole) - LUMO(dipolarophile) interaction is dominant**. The dipole reagent has nucleophilic character and, therefore, electrondonating groups in the 1,3-dipole and electron-attracting substituents in the dipolarophile increase the reactivity. Cycloadditions with diazoalkanes belong to type I. The influence of substituents is shown in Hammett plots for the rate constants of diazomethane Cycloadditions in the 3,4-position of 1-substituted butadienes (p = 4A6; Huisgen et al., 1975), phenylethynes (/?=1.86; Kadaba and Colturi, 1969), and phenylethenes (p = 1.32; Koszinowski, 1980)***. The magnitude of the p values reflects the fact that substituent effects are transmitted better through the short butadiene chain than through the benzene ring. This ring also interferes sterically, as it is placed at the reacting ethene double bond. Cycloadditions of phenyldiazomethanes with substituents in the phenyl ring follow a Hammett relation with a negative p value, as shown by the reaction with ethyl acrylate (p = —1.30; Huisgen and Geittner, 1978). This may be expected, as electron-withdrawing substituents decrease the nucleophilicity at the C-atom bearing the diazo group. Diazoacetates and other diazocarbonyl compounds belong to type II. Azides are also type II dipoles. Type III is represented by 1,3-dipoles like N2O and ozone. Discussion of such dipoles, however, is not within the scope of this book. Returning to diazoalkanes, it is not surprising to see that decreasing their nucleophilicity by introduction of electron-withdrawing substituents in the 1- or 2-position of the alkane chain lowers the cycloaddition rate, as one expects on the basis of the results for substituted phenyldiazomethanes. Examples include the rate of methyl diazoacetate with ethyl acrylate, which is 270 times slower than that of diazomethane, but it seems to be strange that methyl diazoacetate does not give a linear Hammett relationship and, even more interestingly, that its rate with an enamine (1-pyrrolidinocyclohexene, 6.15) is 6710 times faster than that of diazomethane (Reissig, 1978, see also Huisgen, 1984, p. 118, and Huisgen et al., 1979). An explanation of this behavior was possible only after Sustmann and Houk had made their PMO evaluation of 1,3-dipolar cycloaddition. The change from diazomethane to diazoacetate reflects a change from a type-I to a type-II reaction,

* HO, HO,LU, and LU refer to the frontier orbitals of the dipole. ** For an example, we refer to the cycloaddition of diazomethane to ethene, for which Sustmann and Sicking (1987 a) developed an improved perturbation MO program (see Sect. 6.4): HOMO (CH2N2) - LUMO (C2H4) = - 46.2 kJ mol ~l; HOMO (C2H4) - LUMO (CH2N2) = -12.2kJ mor1. *** Hammett plots of the results of these three investigations were published by Huisgen (1984, p. 122).

208

6 Reactions of Aliphatic Diazo and Diazonium Compounds

6.15

i. e., for the latter A^ has a comparable influence on the reactivity compared with that of A^n, whereas A^ can, in a first approximation, be neglected for the reactivity of diazomethane. The increased reaction rate of diazoacetate with an enamine reflects the dominant contribution of A^. Houk's calculations of the HOMO and LUMO orbital energies of parent 1,3-dipoles (Caramella et al., 1977a; Houk and Yamaguchi, 1984, p. 423) show that the replacement of a C-atom by a more electron-attracting, i.e., a more electronegative, heteroatom decreases the interorbital electron repulsion and the orbital energies. As an example, we list in Table 6-2 HOMO and LUMO orbital energies for the stepwise replacement of the CH2 group by an NH group and then of the three N- by O-atoms, i. e., the change from diazomethane to hydrogen azide, to nitrous oxide, and finally to ozone. Table 6-2. HOMO and LUMO orbital energies OP2, ¥3) of diazomethane and its hetero-analogous compounds (after Caramella et al., 1977a; Houk and Yamaguchi, 1984), in kJ mol"1.

LUMO HOMO Cycloaddition type

N=N=CH2

Nr=N=NH

N=N=0

0=0=0

+ 130 -640 I

+ 7.0 -760 II

-78 -850 III

-155 -950 III

It may be added that the differentiation in types I, II, and III and the orbital interaction scheme in Figure 6-1 makes violation of the reactivity - selectivity rule in dipolar cycloadditions at least qualitatively understandable: Faster cycloadditions are more selective. In the following paragraphs, we will discuss some stereospecificities as well as theoretical refinements for a better understanding of experimental results. Stereospecificity is related to retention and inversion of reactant structure during the course of a cycloaddition. Under certain conditions, Stereospecificity is a criterion for the differentiation between a concerted and two types of two-step cycloadditions, as shown in Scheme 6-16 for a 1,2-disubstituted (Z)-dipolarophile. The two-step processes may involve pairs of zwitterionic intermediates (6.16 and 6.17) or biradicals (6.18 and 6.19). A condition for such experiments is, of course, that no (Z)/OE)-isomerization occurs either before or after the cyclization. Formation of the trans-cyclization product in any amount is compatible only with a two-step mechanism. On the other hand, retention of dipolarophile configuration

6.3 Mechanism of 1,3-Dipolar Cycloadditions

209

F\ 6.17 ^"in

a—b=c concerted

c/s

«.,..!?

trans

'

S, 6.18

6.19

is not conclusive for a concerted process. If the rate ratio &i0nic/£rot (or ^rad/^rot) is very large, however, both the two-step mechanism and the concerted pathway lead to the as-product. This criterion was applied to many cycloadditions during the last 60 years. Excluding cases for which inadequate analytical techniques were applied no reaction with stereorandomization was found until 1986. This development culminated in an investigation of Huisgen's group. Bihlmaier et al. (1978) studied the cycloaddition of diazomethane with methyl (Z)- and (J£)-2-butene-2-carboxylate (6.20 and 6.21, respectively) and studied the pyrazolines formed by an NMR — GC technique. The result was that the stereospecificity of the first reaction was found to be >99.94% and that of the second > 99.997%. These values correspond, for the case of a twostep process, to a rate ratio £i0nic//:rot > 1700 and > 33000, respectively. These ratios are so large that a two-step mechanism is unlikely (but nevertheless cannot be absolutely excluded). Analogous investigations with stereoisomerically pure isomers of 1,3-dipoles are possible with substituted ylides and carbonyl ylides. We will mention here only that ^

NCH3

H»,

''C=c'x V

H3C/

COOCH3

6.20

*C=C H

sC 6.21

vNCOOCH3

210

6 Reactions of Aliphatic Diazo and Diazonium Compounds

also in these cases retention was found within the limits of the accuracy of analytical product determinations (see Huisgen, 1984, p. 72-76). It is interesting that Huisgen preferred the concerted pathway since 1960 and defended it (see Huisgen, 1976) against proposals for a two-step diradical mechanism (Firestone, 1968, 1972, 1977) — but it was again Huisgen' s group that found the first case of a two-step cycloaddition (Huisgen et al., 1986 a), namely that of 2,2,4,4,tetramethyl-3-thioxocyclobutan-l-one S-methylide (6.23, obtained from the corresponding 5/?/>o-l,3,4-thiadiazol 6.22 by N2 evolution) combined in situ with dimethyl 2,3-dicyanofumarate. The 1,3-dipole is the sulfur analog of a carbonyl ylide (see Table 6-1). The cis- and frwzs-cycloadducts 6.25 and 6.27 were obtained in a 48 : 52 ratio and in a total yield of 94% in THE The cis /trans ratio in a series of seven solvents reflects a small increase with solvent polarity on the £"T -parameter scale of Dimroth and Reichardt (Reichardt, 1988). The cis/trans ratio ranges from 38 : 62 in CC14 to 62 : 38 in acetonitrile, probably varying due to the solvent effect on the conformational equilibrium between the zwitterions 6.24 and 6.26. The measured rate is that of the dediazoniation step 6.22 -> 6.23. In contrast to the reaction with dimethyl 2,3-dicyanofumarate, the cycloaddition of 6.23 with dimethyl fumarate was found to be stereospecific. No isomerization product (<0.03%) was found. 45 °C

6.22

6.23 (6-17)

6.26

6.3 Mechanism of 1,3 -Dipolar Cycloadditions

211

Cycloadditions of the same thiocarbonyl ylide 6.23 with dimethyl maleate indicated a minor participation of the zwitterionic pathway (cis/trans = 98.9 : 1.1, yield 81%, Mloston et ah, 1989). The basic condition for a two-step mechanism is seen by Huisgen (Huisgen et ah , 1986; Huisgen, 1988) in a strongly dominant HOMO(dipole) - LUMO(dipolarophile) interaction in the transition state. Thiocarbonyl ylides have high MO energy levels, close to those of the allyl anion (review: Huisgen et ah, 1984). On the other hand, 2,3-dicyanofumarates with four electron-attracting substituents have quite different MO energy levels. Fumarates and maleates are less extreme cases. A second reason is the steric shielding of one of the atoms in the thiocarbonyl ylide 6.23, which hinders the concerted addition of fumarates and maleates less than that of the dicyanofumarate. This investigation opened the way to further two-step Cycloadditions of the thiocarbonyl ylide 6.23 with other electrophilic alkenes, e.g., with l,2-dicyano-l,2bis(trifluoromethyl)ethene (Huisgen et ah , 1989). Both the latter dipolarophile and tetracyanoethene demonstrated that, besides the 1,3-dipolar addition product 6.28, the cyclic ketene imine 6.29 is formed in a reversible 1,7-ring closure (6-18, Huisgen et ah, 1986 b, 1989).

/S.

I^Ch^ 6.23

+

,C=C NC

CN

(6-18)

X = COOCH3,CN,orCF3

The question whether the intermediates 6.24 and 6.26 are zwitterions or biradicals has not yet been answered. As known from the tri- and tetramethylene species (see Hoffmann, 1968; Hoffmann et ah, 1970; Hiberty, 1983; Harcourt and Little, 1984; and Ejiri et ah, 1992), zwitterions and biradicals are probably extremes of a structure-dependent degree of charge separation *. Huisgen's experimental evaluation of the thiocarbonyl ylide Cycloadditions allows an understanding of the dichotomy of answers to the question "concerted or two* For the corresponding problem of 1,3-dipoles, see Yamaguchi (1983), Houk and Yamaguchi (1984, Sect. 2.1), and Kahn et al. (1987 a).

212

6 Reactions of Aliphatic Diazo and Diazonium Compounds

step?", which came from MO calculations as discussed earlier in this section. All those theoretical investigations had, as far as we can see, tended towards an "all or nothing" answer. The experiments indicate, however, that the answer is either "concerted" or "two-step" depending on the detailed structure of the reagents with respect to HOMO and LUMO levels as well as of the transition state with the additional consideration of steric hindrance. The lack of experimental and theoretical data of transition states in cycloadditions was emphasized in Houk and Yamaguchi's review (1984, p. 447; see also Houk et al., 1986a, pp. 1110, 1117). Huisgen's work on the concerted/two-step borderline is an important contribution to this field. We think that the use of molecular mechanics (Burkert and Allinger, 1982) may become fruitful for understanding dipolar cycloaddition processes because it allows evaluation of steric interactions on a more quantitative basis *. Finally, the work of Bernardi et al. (1987, 1989) should be mentioned. His group studied the origins of the mechanistic preferences for pathways in cycloadditions by transforming multiconfiguration self-consistent field calculations (MC-SCF) to their equivalent valence bond form.

6.4 Regio- and Diastereoselectivity of Dipolar Cycloadditions with Diazoalkanes If the dipolarophile is assymmetric (d =£ e in d=e, Sect. 6.2, Scheme 6-5), there are two alternatives for the diazoalkane and all other unsymmetrical 1,3-dipoles in their cycloadditions with that dipolarophile. For example, diazomethane and an ethene derivative with an alkyl substituent R may yield the 3- or the 4-alkyl-l-pyrazolines (6-19), or a mixture of both. These primary products rearrange at higher temperature or in the presence of base to give the corresponding alkyl-2-pyrazolines.

a

p

and

°r

(6-19)

* For relatively early examples in cycloaddition chemistry, see Sect. 6.4 (Houk et al., 1986b; Shea and Kim, 1992).

6.4 Regio- and Diastereoselectivity of Dipolar Cycloadditions with Diazoalkanes

213

It is surprising that it has been known for only a relatively short time that in reaction (6-19) only the 3-alkyl-l-pyrazoline can be found if simple alkenes (hex-1-ene, R = C4H9, and allylbenzene, R = C 6 H 5 -CH 2 -) are used (Huisgen et al., 1980). At the same time, however, Firestone (1980) reported an 86 : 14 ratio for 4,5-dihydro-3and 4,5-dihydro-4-methyl-3//-pyrazole for the reaction with propene (R = CH3), whereas Huisgen et al. (1980) found only addition of propene in the 3-methyl mode when using 2-diazopropane. These authors also obtained the same regioselectivity for reactions of 2-diazopropane and ethyl diazoacetate with hex-1-ene and allylbenzene. Ethoxyethene forms 3-ethoxy-4,5-dihydro-3//-pyrazole with diazomethane (Firestone, 1976), but ethoxyethyne inverts the regiochemistry and gives, after aromatization, a 4:96 mixture of 3- and 4-ethoxypyrazole (6-20, Sustmann et al., 1990).

(6 20)

'

96%

4%

The influence of substituents in alkynes is also demonstrated by Padwa and Wannamaker (1990) for the reaction of 2-diazopropane with aryl-ethynyl sulfones (6.30), substituted in the 2-position with either a methyl, phenyl, or trimethylsilyl group. As shown in (6-21) addition of the aryl 2-(trimethylsilyl)ethynyl sulfone takes place with a specificity that is the reverse of that of the compounds containing a methyl or phenyl group in the 2-position.

SOaAr

(6-21)

ArO2S

In the context of the ethynyl sulfones 6.30 Padwa's Cycloadditions of phenylsulfonyl-substituted propa-l,2-dienes like 6.31 with diazomethane should be mentioned briefly (Padwa et al., 1993a, with many references on allenes used as dienophiles). The example in (6-22) demonstrates the regiospecificity of the cycloaddition to the more reactive electron-deficient n bond. The ready reactivity of cumulated double bonds is based on the relief of strain when the 1,2-propadiene

214

6 Reactions of Aliphatic Diazo and Diazonium Compounds

CH2=C=C

« n rH b<J 2U6H5

CH2N2

H2C

S02C6H5

6.31 (6-22)

H3C

S02C6H5

undergoes the addition reaction. This cycloaddition is also a fine example of an aromatization of the primary dihydropyrazole by two proton shifts. Intramolecular dipolar cycloaddition may also result in products that do not correspond to experience with related intermolecular cyclizations. An example is the intramolecular reaction of 6-diazohex-l-ene (6.32), which was investigated by Kirmse and Grassmann (1966). This reaction leads to 2,3-diaza-bicyclo[3.3.0]oct-2-ene (6.34), i. e., with a regioselectivity that corresponds to the formation of a 4-alkyl-lpyrazoline. N N 6.32

6.33 (6-23)

6.34

The approximate representation of the transition state 6.33 demonstrates that the principally also conceivable reverse cycloaddition could result in a strained ring system. More important than this explanation is the conclusion that the "wrong" regiochemistry of this reaction does not need much more activation energy than that of the expected cyclization. If, for example, the regioisomer ratio in intramolecular cycloadditions were 98 :2, i. e., when the minor product can be detected only with much analytical effort, the activation energy for the minor product is only 10 kJ mol"1 higher than that of the main product. Can we understand regioselectivity effects on the basis of theory? The examples of experimental results discussed earlier in this section and the fact that an energy

6.4 Regio- and Diastereoselectivity of Dipolar Cycloadditions with Diazoalkanes

215

difference of 10 kJ mol"1 (or less) is sufficient to obtain 3- or 4-substituted 1-pyrazolines are a challenge for theory and lead to doubts at the same time. As discussed in Section 6.3, frontier orbital calculations including perturbation (PMO) allow us successfully to understand 1,3-dipolar additions. On the other hand, however, these calculations result in small differences &E (Fig. 6-1) of large energies (HOMO and LUMO). These small values are, in most cases still larger than the 10 kJ mol"1 difference in which we are interested when we evaluate regioselectivities. Nevertheless, regioselectivity was discussed — successfully — in one of the pioneering papers on the theory of 1,3-dipolar cycloadditions. Houk et al. (1973 b) postulated "that the preferred regioisomeric transition state will be that in which the larger terminal coefficients of the interacting orbitals are united, and the propensity for addition in one direction will depend on the difference in the squares of the terminal coefficients". This statement is shown by Houk et al. in a figure that depicts transition state (A) to be more stable than (B) (Fig. 6-2). The large —large orbital overlap between atoms a and d in (A) initiates bond formation at a greater distance and earlier than that of the two small —large interactions in (B).

Fig. 6-2. Scheme representing stabilization of regioisomeric transition states in 1,3-dipolar cycloadditions (after Houk et al., 1973 b).

The frontier orbital energies for diazomethane and a series of substituted ethenes as dipolarophiles result in two conclusions: (1) Those reactions with unsubstituted ethene and with its derivatives containing a conjugated (e.g., CH2 = CH— in butadiene) or an electron-withdrawing substituent are controlled by the HOMO(dipole) - LUMO(dipolarophile) overlap, those with electron-rich dipolarophiles (e. g., ethoxyethene) are predicted to follow clearly the reverse overlap, and in alkyl-substituted ethenes both modes are approximately equally important. (2) With respect to reactivity, highest cyclization rates are calculated for ethenes with electron-withdrawing substituents, followed by electron-rich ethenes and those with conjugating groups. For ethene and alkylethenes, the rates are lowest. Eleven years later, Houk and Yamaguchi (1984, p. 442) stated that, with respect to FMO analysis of regioselectivity and reactivity for diazonium betaines, "it had not yet been necessary to change this description in any substantial way". We agree, if this statement refers to basic principles (application of frontier orbital concepts), but

216

6 Reactions of Aliphatic Diazo and Diazonium Compounds

not so much if specific cases of regioselectivity, such as some of those discussed in the introduction of this section, should be evaluated, e.g., the reaction of diazomethane with ethoxyethene, for which an unexplained discrepancy between experiment and theory exists, but also for several cases where steric hindrance was postulated (see Huisgen's review, 1984, p. 141). Steric factors are well known as being hardly accessible to theory, but an accurate quantification of electronic effects, compared with experimental data, would allow evaluation of the steric contribution to the experimental result. Therefore, Sustmann felt that it would be desirable to devise a more comprehensive explanation of the regioselectivity in the cycloaddition of diazomethane. Sustmann and Sicking (1987 a) developed a program, called PERVAL (perturbation + ev#/uation) that makes use of graphical evaluations of the numerical results. Its fundamental perturbation theory is based on the MINDO/3 approximation. The program allows differentiation between covalent and noncovalent interactions in a molecular complex (see, for its first application for cycloadditions of formonitrile oxide, Sustmann and Sicking, 1987 b). On this basis Sustmann and Sicking (1987 c) evaluated first the addition of diazomethane to ethene. MINDO/3 calculations gave heats of formation of 114.6 kJ mor1 for CH2N2, 98.4 kJ mol'1 for ethene, and 328.2 kJ mor1 for a transition state in which the distance between the molecules is 225 pm. The perturbation energies between the reactants were calculated to be 197.5 and -78.8 kJ mol"1 for the first- and second-order contribution, respectively. The sum of A//f for the reactants plus the two perturbation contributions is therefore 331.7 kJ mol"1 — in very good agreement with the A//f value for the transition state. The HOMO — LUMO interactions are calculated to be -46.2 kJ mol"1 for HOMO(CH2N2)LUMO(C2H4) and -12.2 kJ mor1 for HOMO(C2H4) - LUMO(CH2N2). The sum of these two stabilizations places emphasis on the importance of HOMO — LUMO interactions, but they are not the only interactions, as this sum corresponds to about three quarters of the total second-order stabilization. The calculations showed also that the more the angle C-N-N of diazomethane bends from 180° to 130°, the more favorable the HOMO - LUMO stabilization will become. These very promising results were then applied to diazomethane cycloadditions with ethene derivatives, monosubstituted with a methyl, methoxy, phenyl, ethenyl or a methoxycarbonyl (COOCH3) group, or 1,2-disubstituted ethenes with phenyl and COOCH3, or methyl and COOCH3 groups, or 1,1-disubstituted with two COOCH3 groups. How well do the experimentally observed regioselectivities agree with the calculated main interaction, i.e., with the HOMO(CH2N2)-LUMO(C2H2XY) energy difference between the two regioisomer additions? These energy pairs show differences of 0.4 kJ mol-1 for X = 1-H, Y = 2-CH3, to 3.3 kJ mor1 for X = 1-H, Y = 2-COOCH3, for X = 1-CH3, Y = 2-COOCH3, and for X = 2-CH3, Y = 2-COOCH3. These differences should reflect expected regioisomer ratios (see earlier in this section). They are smaller than the corresponding values that can be deduced from data given by Houk et al. (1973 b). The particularly small difference calculated for the cycloaddition with propene (X = 1-H, Y = 2-CH3) is in accordance with experiment in a remarkable way. Methoxyethene remains, however, the

6.4 Regio- and Diastereoselectivity of Dipolar Cycloadditions with Diazoalkanes

217

outstanding exception as calculations clearly favor "normal" 3-addition. The cycloaddition rate of propene fits, however, the correlation of calculated secondorder interactions well. The improvement can be seen also from a plot of log k values for all nine cycloadditions against the calculated interactions. The regression coefficient of this plot is better (r2 = 0.94) than that for an earlier correlation with CNDO/2 interaction energies (Sustmann et al., 1977, r2 = 0.86). In conclusion, the incorporation of noncovalent interactions in Sustmann's PERVAL method extends the theoretical approach to reactivity and, to a certain extent, to regioselectivity in cycloadditions. These repulsive forces are electrostatic in nature and, therefore, their range reaches further than that of the covalent interactions. At the same time the groups of Gandolfi and Rastelli published a joint investigation (Burdisso et al., 1987) on the theory of diazoalkane cycloadditions to a wide group of mono- and disubstituted alkenes. This work is based on the calculation of nonfrontier charge-transfer (CT) interactions, because the authors feel that "the practical use of FMO theory has reached such a high degree of Versatility' as to account for whatever experimental result one has to handle". Their own calculations indeed lead to better correlations between log k of cycloaddition rates and CT interaction energies - but only after introduction of empirical reduction parameters! The recent paper of Sustmann and Siangouri-Feulner (1993) on [4 + 2] cycloadditions contains general comments to the application of FMO methods which are also valid for 1,3-dipolar cycloadditions. It would appear, however, that Gandolfi and Rastelli did not directly continue the work discussed in their paper of 1987, but in a very recent paper they included a study on the 1,3-dipolar cycloaddition of methoxyethene with diazomethane and with formonitrile oxide (Rastelli et al., 1994). This investigation is a continuation of a series of seven publications of these authors, published since 1990 and is based on a procedure that rests on the intuitive concepts of classical stereo — electrostatic repulsions and of vicinal delocalizations. Vicinal (repulsive) interactions between bonding and antibonding orbitals originating from closed-shell repulsions and from electrostatic interactions have already been considered to play a role in the staggered model of Houk et al. (1983a, 1983b), and by Hehre's group (Kahn et al., 1987b; Kahn and Hehre, 1987), respectively*. The investigation of Rastelli and coworkers was based on geometry and transition state calculations at various levels of theory (AMI, HF/STO-3G, HF/3-21G, and HF/6-31G*). It was found that the transition states for the formation of both regioisomers, i.e., the 3- and 4-methoxy-l-pyrazolines (see Scheme 6-19, R = OCH3), exist in two conformations. Both conformations of the transition states leading to 3-methoxy-l-pyrazoline are strongly preferred. This result is consistent with the experimental result for the corresponding reaction with ethoxyethene (see earlier in this section). Recently, Sustmann's group, in collaboration with Huisgen, also presented another computational approach to cycloaddition chemistry that reflects the rapid development in more and more sophisticated computer applications (Sustmann etal., 1993). * In a recent paper of Houk's group (Wu et al., 1993), electrostatic interactions are considered as being closely related to FMO theory.

218

6 Reactions of Aliphatic Diazo and Diazonium Compounds

The subject of this investigation is the cycloaddition of diazomethane to thioformaldehyde and thioketones (R2C = S, R = H, C2H5, 2-C3H7, tert-C4H9). These dipolarophiles are interesting for two reasons: they are extremely reactive (see Huisgen and Li, 1983; Huisgen and Langhals, 1989) and their cycloaddition with diazomethane leads to a mixture of the two regioisomers, 1,3,4- and 1,2,3-thiadiazoline 6.35 and 6.36, respectively (Krapcho et al., 1974). The ratio 6.35/6.36 depends strongly on solvent polarity and on steric effects of the groups R (Mloston and Huisgen, 1989).

S

1— R

R

(\ S

R-A

R

6.35

6.36

Sustmann et al. (1993) applied both semiempirical MNDO-AM1 and -PM3 calculations and ab initio RHF and CASSCF calculations on different levels (3-21G* 6-31G*). Most interesting are the results on the cyclization mechanism with thioformaldehyde (R = H): The ab initio techniques suggest that both regioisomers should be formed in a concerted way, but with MNDO-AM1 and -PM3 a concerted cyclization is predicted only for the 1,3,4-thiadiazoline 6.35. The 1,2,3-thiadiazoline 6.36 should be formed via a planar intermediate of type 6.37 in which the distance between the two C-atoms is calculated to be 327 pm (PM3) or 366 pm (AMI)*.

I I x-\

n^o

. /•>! I

ori2

6.37

The (extended) differential discussion of the results led the authors to the conclusion that the ab initio calculations are in better agreement with experiments (solvent effect and influence of substituents on regioisomer ratio) than the AMI and the PM3 results. Related reactions of diazoalkanes were investigated with 4,4'-dimethyl-l,3-thiazol5(4//)-thiones 6.38 by Heimgartner, Mloston and coworkers. 2-Diazopropane forms 2,5-dihydro-l,3,4-thiadiazoles 6.39 followed by a rapid dediazoniation process via thiocarbonylides 6.40 (6-24) (Mloston and Heimgartner, 1992). Diazomethane gave a mixture of 1,4-dithiane 6.42 (20%), 1,3-dithiole 6.43 (19%), thiirane 6.44 (22%), 4,5-dihydro-5-methylidene-l,3-thiazole 6.45 (ca. 6%), and thiazolone 6.46 (ca. 2%), when 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione (6.41, R = C6H5) was used * Caramella et al. (1977b) found already that semiempirical methods have a tendency to favor intermediates.

6.4 Regio- and Diastereoselectivity of Dipolar Cycloadditions with Diazoalkanes

219

(6-25, Kagi et al., 1993). The thiirane 6.44 loses sulfur easily, as found earlier in the similar reaction sequence with 2-diazopropane (6-24). With di(tert-butyl)diazomethane the spiro compound corresponding to the 2,5-dihydro-l,3,4-thiadiazole 6.39 is sufficiently stable to be analyzed by 13C NMR spectroscopy and by X-ray diffraction (Mloston et al., 1994).

(6-25)

6.44

6.45

6.46

Heimgartner's group investigated also the analogous thiirane formation of l,3-thiazole-5(4#)-thiones 6.41 with phenyldiazomethane (Petit et al., 1994) and found the diastereoisomeric trans- and c/s-thiiranes 6.47 and 6.48, respectively. They can be desulfurized stereospecifically with triphenylphoshine to the (E)- and (Z)-benzylidene derivatives 6.49 and 6.50, respectively. Reaction of the same thiazole —thiones 6.41 with ethyl diazoacetate gives, however, a complex mixture of seven products (Kagi et al., 1994). Vasella and his coworkers explored the preparative potential of another type of thiocarbonyl compound, namely the glyconothio-O-lactone 6.51, as dipolarophile in

220

6 Reactions of Aliphatic Diazo and Diazonium Compounds

R—^

J

+

^C^

_N2 > R^

^7

C6H5 + R^ 'S^H

6.41

6.47

°

J^ V

H C6H5

6.48 (6-26)

6.49

the reaction with diazomethane. The primary products were derivatives of 2,5-dihydro-l,3,4-thiadiazole (6.52) and 4,5-dihydro-l,2,3-thiadiazole (6.53) which, after treatment with triethylamine and pyridine, respectively, gave the hydroxythiadiazole 6.54 and 6.55. In mild thermolytic processes, the two dihydrothiadiazoles 6.52 and 6.53 lose N2.

6.51

6.52

6.53

There is interest in cycloaddition of diazoalkanes to cycloalkenes for various reasons. Small rings (cyclopropene and cyclobutene) react easily and often in good yield as a result of their angle-strained double bond. Their products with diazomethane, 2,3-diazabicyclo[3.1.0]hex-2-ene (6.56) and 2,3-diazabicyclo[3.2.0]hept2-ene (6.57) and their substituted derivatives are interesting for synthetic purposes, e. g., by azo-extrusion leading to ring contraction. With substituted cyclopropenes and a-substituted diazoalkanes epimer and regioisomer mixtures are obtained. In most cases, the ratios of products are in-

6.4 Regio- and Diastereoselectivity of Dipolar Cycloadditions with Diazoalkanes

6.56

221

6.57

fluenced predominantly by steric factors, as shown, for example, in the formation of a 60:40 mixture of eAro/e«^o-4-methyl-2,3-diazabicyclo[3.1.0]hex-2-ene (6.58/6.59) in the reaction of diazoethane with cyclopropene. This reaction was investigated by Hammond's group (Eaton et al., 1972). A methyl group at one of the sp2-C-atoms of cyclopropene leads to a regioisomer mixture of 1- and 5-methyl-2,3-diazabicyclo[3.1.0]hex-2-ene in a 2:1 ratio with diazomethane (Zaitseva et al., 1975). H

3Cx

/\

/

,

(6-28)

6.59

An interesting reaction that is not easy to understand is the cycloaddition of diazoalkanes to os-3,4-dichlorocyclobutene (6.60). Franck-Neumann (1969) found that the diazomethane was unexpectedly added on the sjw-diastereotopic side of this dipolarophile (6.61). Martin's group (Landen et al., 1988a, b; Hake et al., 1988) confirmed this result for diazomethane and 12 monosubstituted diazomethane derivatives. anti-Addition (6.62) was found only for disubstituted diazomethanes RR'C = N2 (R and R' = CH3, C6H5) and for diazofluorene.

(6-29)

6.62

In spite of the fact that these authors also included investigations on the stereoand regioselectivities of Cycloadditions of cyclobutenes substituted with other groups (CH3S: Landen etal., 1988 b; CH3O, COOCH3, -O-CO-O- and -O-CO- : Hake et al., 1988), no convincing general basis (or bases) for the selectivity effects was found. Gandolfi and Rastelli's groups (Burdisso et al., 1988 a) investigated Cycloadditions of diazomethane to two bicyclic systems, bicyclo[3.2.0]hept-6-ene (6.63) and 2,4-dioxabicyclo[3.2.0]hept-6-ene (6.64). They also investigated the reaction of c/5-3,4-(diacyloxy)-cyclobutenes (Burdisso, 1988 b).

222

6 Reactions of Aliphatic Diazo and Diazonium Compounds

O

& 6.63

6.64

It is well known that the reactivity of ring-strained cycloalkenes with various 1,3-dipoles is higher than that of simple unstrained cycloalkenes (for CH2N2: cyclopentene k = 0.27 x 10~3 M -1 s"1; cyclohexene k = 0.4 x 10~3 M ~l s"1, Geittner et al., 1977). An extended and systematic investigation including regioselectivity and theoretical calculations has, as far as we are aware, only been undertaken for cycloadditions of 2,4,6-trinitrophenyl azide (Shea and Kim, 1992) * Shea and Kim's work includes (^-cycloalkenes, bicyclic alkenes and bridgehead alkenes. Changes of strain energies (ASE) on going from reactant to product were evaluated by molecular mechanics (MM2), and a good correlation (r = 0.96) was obtained for a plot of log k versus the calculated relief of strain energy. For bridgehead alkenes, the authors found a reversal of the normal trend of regioselectivity. An analogous investigation of diazoalkane cycloadditions would be welcome! The reactions of 1,4-benzoquinone with diazoalkanes have a long history since the pioneering work of von Pechmann and Sell (1899). It seems that the cycloaddition with diphenyldiazomethane at the first C=C bond does not decrease the reactivity of the first isolated compound 3,3-diphenyl-3//-indazole-4,7-diol (6.66, formed by dienolization of the pyrazoline 6.65), because secondary products, namely 3,3-diphenyl-7-(diphenylmethoxy)-3//-indazol-4-ol (6.67) and 8-(diphenylmethoxy)3,6-dihydro-3,3,5,5-tetraphenylbenzo[l,2-c;5,4-c']dipyrazol-4-ol (6.68) were also found (Fieser and Peters, 1931). The regioselectivity of CC versus CO addition was investigated by Oshima and Nagai (1988) for a series of six 1,4-benzoquinone derivatives, substituted in the 2-, 2,3-, 2,5-, 2,6-, 2,3,5-, and 2,3,5,6-positions by the corresponding number of Cl-atoms. The results show a steady change of the regioselectivity from CC to CO addition. As this trend is in contradiction to MNDO - FMO calculations, the authors assume that this discrepancy is due to steric repulsion by the chloro substituents. It stands to reason that norbornene, for decades the favorite hobby horse for many physical organic chemists, studied in reactions with several 1,3-dipoles, leads to exo adducts. endo-Isomers are formed (besides exo) in substituted norbornenes. A relatively recent investigation of 2-diazopropane cycloaddition to norbornene, the endo- and exo-isomers of 5-methyl-, 5-phenyl-, and 5-(methoxycarbonyl)norbornene, and other bicyclo[2.2.1]hept-2-enes (Majchrzak and Warkentin, 1990) is interesting because the results are consistent with a concerted mechanism, but allow the conclusion that CC bond formation runs well ahead of NC bond formation. This explains the observed regioselectivity. Figure 6-3 represents the situation of partially formed CC and CN bonds leading to the two regioisomers by addition of 2-diazopropane in the exo-position. For structure A, a relatively large nonbonded * Kinetics of cycloadditions with the unsubstituted cycloalkenes C5H8-C8H14, including 1-methylcyclopentene and -heptene were measured earlier by Baily and White (1966).

6.4 Regio- and Diastereoselectivity of Dipolar Cycloadditions with Diazoalkanes

223

6.66 + (C6H5)2CN2

1

-N 2

_

(6-30)*

H

H5C6

6.68

6.67

Fig. 6-3. Interaction between encircled groups as source for asynchronous formation of CC and CN bonds in concerted cycloadditions of 2-diazopropane to substituted norbornenes: — earlier than (after Majchrzak and Warkentin, 1990).

interaction between the encircled H-atom and the encircled substituent R is present, if this C-atom of the norbornene is becoming bond to the C-atom of the dipole (which is expected for a type-I cycloaddition; see Sect. 6.3). This 'Interaction is smaller for the reverse addition of the dipole (structure B). Indeed, the isomer ratio of the regioisomers is in favor of the latter (B/A = 1.35-1.61, depending on substituent R). If R is in the exo position, however, the ratio B/A is 1.0 ± 0.05, i.e., R has no influence on the regioselectivity. If the CC bond is better developed in the transition state than the CN bond, the regioselectivity thus can be explained. * For further products, see Oshima and Nagai (1988).

224

6 Reactions of Aliphatic Diazo and Diazonium Compounds

Diastereomeric cycloadducts are obtained when the dipole and the dipolarophile each form a chiral center in the cyclization reaction. Two different types of diastereospecificity occur in dipolar cycloadditions: 1) The 1,3-dipole reagent bears a terminal C-atom with two different substituents, and the dipolarophile bears two such substituents at each reacting atom. In addition to the two regioselective approaches of the two reagents two diastereomeric adducts are feasible, as shown in Scheme 6-31. This type of diastereospecificity was investigated in detail with nitrones (see Gree et al., 1975; Joucla and Hamelin, 1978). 2) The two faces of the dipolarophile are not equivalent for the suprafacial addition of the dipole. Additions to c/s-3,4-disubstituted cyclobutenes belong to this group. 3) The oldest known type of diastereoselectivity is the addition to dipolarophiles that form chiral centers at the reacting atoms. In the context of Buchner's pioneering work on cycloaddition of diazoalkanes (see Sects. 1.1 and 6.2), Buchner investigated the reactions of methyl diazoacetate with ethyl (E)-3phenylprop-2-enoate (ethyl cinnamate) and of ethyl diazoacetate with methyl (J5T)-3-phenylprop-2-enoate (Scheme 6-31) with his coworkers Dessauer (1893) and von der Heide (1902). They found two isomeric 4,5-dihydro-3//-pyrazoles 6.69 and 6.70 * which, on dehydrogenation, gave the same prototropic mixture of ethyl methyl 4-phenylpyrazole-3,5-dicarboxylates (6-32). The ratio found was 80:20. This surprising result was rationalized 78 years after Buchner's discovery: Eberhard and Huisgen (1971) repeated Buchner's work. They corroborated the ratio mentioned, but they also found a third isomer, 6.76, in a yield of 10%, i. e., a product of the opposite regiochemistry. If the ester alkyl groups of the two reagents were exchanged, the two pyrazolines 6.69 and 6.70 were obtained in a ratio of 20:80 with 9% of 6.77, i. e., again a regioisomeric product. The inverse ratios 80:20 and 20:80 .N

N MM

\\4

//ii0 u j W"5

H""}

H5C2OOC

H

6.76

McOpv-'^Jvy~«-»y^/'

\\4

Uiii

MM I/

rt jI

H3COOC

n |_, U M

6 5

H

6.77

indicate that methyl and ethyl esters have the same effect. The three 4,5-dihydro-3//-pyrazoles 6.69-6.71 are those expected if methyl- and ethyl (£')-3-phenylprop-2-enoate do not isomerize into the corresponding (Z)-compounds during cycloaddition. Obviously the base attacks the 4,5-dihydro-3/f-pyrazoles from the less hindered side in the protomerization to the corresponding 4,5-dihydrol//-pyrazoles, otherwise the c/s-4,5-disubstituted compounds 6.72 and 6.75 should also be detectable. The yields of the two 4,5-dihydro-l//-pyrazoles 6.73 and 6.74 allow calculation of the rate ratios k(syri)/k(anti) = k'(syn)/k'(anti) = 1.5. The structures of the transi* Structures assigned by Brey and Jones (1961).

6.4 Regio- and Diastereoselectivity of Dipolar Cycloadditions with Diazoalkanes

I

if *

"'I

2^«S

* I-' T " 9,

«!

tn

^

iZ

^

+z

o

i

^

C?

II IO

8

\ / O

- x

x

im

.CM

__

/

/ "^

\

-f

12 |

H

''l-T-

CO

'

*

o

225

226

6 Reactions of Aliphatic Diazo and Diazonium Compounds H N— N

H N— N

(6-32)

tion states 6.78 and 6.79 for the cycloaddition in the syn- and anti-mode, respectively, provide an explanation for the result that these ratios are significantly different from unity. Overlap of n orbitals between the phenyl ring and the carbonyl group of the esters leads to an attraction of these substituents in the syn transition state (6.78). On the other hand, there is also a repulsive interaction caused by steric hindrance between these syn groups. This effect becomes dominant if tert-butyl diazoacetate is used instead of the methyl ester. The corresponding isomeric 4,5-dihydro-l//-pyrazoles 6.73 and 6.74 ((CH3)3C instead of C2H5) are formed in a ratio 34:66, corresponding to k'(syri)/k'(anti) = 0.47*. .COOR 'COOR L

H-C=C 6.78 syn

6.79 anti

More recently, Houk et al. (1986 b) demonstrated that the steric interaction in dipolar cycloaddition can be reproduced by molecular mechanics calculations (MM2) of transition state models. These calculations are in good agreement with experimental diastereomer ratios in the reaction of 4-nitrobenzonitrile oxide with various 3-substituted but-1-enes. A stereochemically interesting observation was made by Carrie's group (Vebrel et al., 1987) in their investigations of diazomethane cycloaddition to methyl l,2-dihydronaphthalene-3-carboxylates substituted at the 1- or 2-position by alkyl or phenyl groups. The 4,5-dihydro-3//-pyrazoles were isomerized into the l//-isomers for easier identification by *H NMR spectroscopy, in part also by X-ray analyses (6-33). The preferred conformations for the dihydronaphthalenes are 6.80 and 6.81 for the compounds with a substituent in the axial- (i. e., 2-) and pseudoaxial (i. e., 1-) positions, respectively. As shown in (6-33) and (6-34) dihydronaphthalenes with a substituent in either position undergo addition of diazomethane from the less hindered face opposite to that substituent. * For further examples that demonstrate different interactions with other reactants, see Huisgen and Eberhard (1977).

6.4 Regio- and Diastereoselectivity of Dipolar Cycloadditions with Diazoalkanes

227

(6-33)

,COOCH3 (6-34)

The interesting observation mentioned above relates to diazomethane cycloaddition to the chromium (tricarbonyl) (methyl l,2-dihydro-te#o'-2-methylnaphthalene3-carboxylate) complex 6.82 (6-35). This chromium complex yields a mixture of the diastereomeric pyrazolines 6.83 and 6.84 in a ratio 92:8. The latter isomer corresponds to the pyrazoline formed with the uncomplexed methyl l,2-dihydro-2-methylnaphthalene-3-carboxylate (6.80, R = methyl), as major product. The corresponding chromium complex of the methyl

(6-35)

OC—Cr OC 6.83

CO 6.84

228

6 Reactions of Aliphatic Diazo and Diazonium Compounds

l,2-dihydro-e«rfo'-2-methylnaphthalene-3-carboxylate undergoes addition of diazomethane, however, with high diastereoselectivity and forms the same product as the uncomplexed compound. The configuration of 6.83 was established by X-ray analysis (Mercier et al., 1983). The presence of the bulky Cr(CO)3 group results in dominant inversion of the cycloaddition selectivity.

6.5 Cycloaddition Reactions with Diazoalkanes in Organic Synthesis Some years ago, Huisgen et al. (1987 b) mentioned that diazoalkane cycloadditions to electron-deficient CC multiple bond compounds and other dipolarophiles represent the class of [3+2] cycloadditions that has been most intensively studied for synthetic purposes. This is also evident from the reviews that concentrate on preparative aspects of diazoalkane cycloadditions (Regitz and Heydt, 1984; Stanovnik, 1991). Yet, in contrast to these statements, not a single 1,3-dipolar cycloaddition with a diazoalkane is reported in Organic Syntheses!* The plethora of such reactions is bewildering. This becomes clear from Regitz and Heydt's review: in a total of 148 pages it contains 714 references. Not taking into account the table of contents and the list of references, two thirds of the text consist of formulae, schemes, and tables, and only one third is proper text. In other words, very little text is given for each reference. The review is organized into 27 sections, each covering a different type of dipolarophile, namely 11 systems with C = C and double bonds involving hetero atoms (from >C = N— to O2), 13 sections on heterocumulene systems like ketenes, CS2, isocyanates, etc., and 3 systems with triple bonds. The review of Stanovnik (1991) concentrates on diazoalkane additions to some nitrogen containing heteroaromatic systems, namely to monocyclic pyridazines, and to bicyclic and polycyclic azolo- and azinopyridazines with a bridgehead N atom. In this section, we will discuss some general aspects of synthetic applications and provide examples, including their use in synthesis of natural products. Buchner accomplished the first synthesis of pyrazole by a cycloaddition in 1889, but not by the direct reaction of diazomethane and ethyne, but with methyl diazoacetate and an electron-deficient dipolarophile, ethynedicarboxylate (see Sect. 6.2). Unsubstituted ethene and ethyne were considered for a very long time to be not sufficiently reactive for synthetic purposes, although von Pechmann (1898 b) had reported a 50% yield of pyrazole from diazomethane and ethyne shortly after the discovery of diazomethane. The knowledge of diazomethane being explosive is probably the reason that the obvious advantage of a reaction under pressure in order * Padwa's recent review in Comprehensive Organic Syntheses (1991 a) indicates, however, a certain saturation with respect to cycloadditions of diazoalkanes relative to those with other 1,3-dipoles. For an older review, see Wulfman et al. (1978, p. 824).

6.5 Cycloaddition Reactions with Diazoalkanes in Organic Synthesis

229

to obtain a higher rate and yield was investigated only much later: Reimlinger (1959) obtained pyrazole in 95 % yield in an ether solution of ethyne and diazomethane, and Huisgen et al. (1980) synthesized 4,5-dihydro-3//-pyrazoles analogously from ethene and diazomethane. This procedure is also applicable to alkylated ethenes, as shown by de Suray et al. (1974) for phenylated ethenes, and even for a phenanthrene derivative. The high regioselectivity (see Sect. 6.4) is welcome for preparative purposes. The 3-alkyl-4,5-dihydro-3/f-pyrazoles rearrange with HC1 to give high yields of 3-alkyl-4,5-dihydro-l/f-pyrazoles, which can be easily dehydrogenated with sulfur to give 3-alkylpyrazoles. The primary 4,5-dihydro-3//-pyrazoles often escape isolation by tautomerization to the 4,5-dihydro-l/f-pyrazoles. 1,3-Dienes give complex mixtures of products that are not interesting for preparative purposes. Substituted ethyne cycloadditions have been rarely used. The regioselectivity is high (6-36). The primary 5-substituted 3//-pyrazoles (6.85) rearrange easily into the corresponding l//-pyrazoles (6.86) if at least one R is hydrogen. The yields are not predictable, however, e. g., for the reaction of diazomethane with phenylethyne it is only 30% (Kirmse and Horner, 1958), but with (4-nitrophenyl)ethyne it is 92% (Manecke and Schenck, 1959). Yields with carbonylalkynes (R-CO-C = CH) are generally high.

Ar-C=CH

+

)C=N2 R'

R, R' = H, alkyl, aryl

6.85

The reaction system (6-37) includes the thermal azo-extrusion * of a cyclic azo compound to a cyclopropane derivative and the "direct" formation of cyclopropanes, catalyzed by metal complexes. Synthetic routes to cyclopropane derivatives became an important subject in the last two decades, and one frequently used method is the 1,3-dipolar cycloaddition of a diazoalkane to an alkene followed by thermal or photolytic azo-extrusion of the 4,5-dihydro-3//-pyrazole formed to the cyclopropane derivative (6-37 A). This route can be followed in many cases without isolation, or even without direct observation, of the 4,5-dihydro-3//-pyrazole. Therefore, it is formally very similar to cyclopropane formation from alkenes with diazoalkanes, in which a carbene is first formed by azo-extrusion of the diazoalkane (see Sect. 8.3). As shown in pathway (6-37 B), this step can be catalyzed by copper, palladium, or rhodium complexes (see Sects. 8.2, 8.7, and 8.8). There are cases where it is not clearly known whether route A or B is followed **. Scheme 6-37 also includes * IUPAC rules (IUPAC 1989 c, p. 753) state that azo-extrusion is written with a hyphen. The terms denitrogenation and nitrogen extrusion, both used by Adam et al. (1992, 1993) and Adam and Sendelbach (1993) should not be used. They are superfluous and ambiguous. ** For examples of cyclopropanation of alkenes by diazoalkanes that are catalyzed by metal complexes [Mo(CO)6] and [Mo(AcO)4], but that follow the dipolar cycloaddition - azo-extrusion pathway see Doyle et al. (1982 a).

230

6 Reactions of Aliphatic Diazo and Diazonium Compounds

a third alternative (C), namely a pyrazoline side equilibrium (reversible first step of pathway A, dashed arrow), and an azo-extrusion of the 4,5-dihydro-3//-pyrazole (second step of A) that is much slower than pathway C, consisting of a primary dediazoniation of the diazoalkane into a carbene followed by cyclopropanation by the carbene. This pathway has not, as far as we know, been either discussed or found. As we have shown for other reactions in volume 1, (Zollinger, 1994, p. 364, Schemes 12-74 and 12-75), it is not possible to distinguish, by kinetic methods, pathways involving side equilibria from those with intermediates. It may be possible, however, to achieve a decision by a comparative evaluation of structural effects if a series of carefully designed reagents is chosen or if the alternative pathways are evaluated by a theoretical approach (see also the discussion of C60 reactions with diazoalkanes in Sect. 8.4).

(6-37)

An instructive example for pathway 6-37 A was found by Franck-Neumann and Miesch (1984). Reaction (6-38) demonstrates that the cycloaddition with 2-diazopropane takes place, as expected, at the double bond of methyl 5-methylhexa-2,4-dienoate (6.87) substituted by the (electron-withdrawing) ester group. The intermediate dihydropyrazole can be isolated. It is interesting, however, that in the subsequent azo-extrusion leading to the substituted cyclopropane carboxylate 6.88 (trivial name: crysanthemic ester), the cis/trans ratios of the thermal, of the photolytic (high pressure Hg lamp), and of the benzophenone-sensitized photolytic methods are very different, in spite of the yield being the same (90%).

COOCHg

+

(H3C)2C=N2

-

^^^Ly^

6.87

6.88

A (HOt)) cis/trans = 2:1 photolysis " = 4:1 photolysis, sens. " = 0.25 : 1

(6-38)

6.5 Cycloaddition Reactions with Diazoalkanes in Organic Synthesis

231

In general, photolytic azo-extrusion from 4,5-dihydro-3//-pyrazoles is superior to thermolysis. Photolysis was introduced as a method for synthesis by Jeger's group (Kocsis et al., 1960). The configurations of the products in the thermolysis, in the direct photolysis, and in the sensitized photolysis are often quite different. Cyclopropanation for the synthesis of alkyl cyclopropanes via dihydropyrazoles is preferred to the direct route via carbenes, because, in the latter, the C - H insertion of the carbene into the alkyl group is faster than the Cyclopropanation. The dihydropyrazole pathway was used in particular for the formation of highly strained bicyclo [1.1.0] butanes (Franck-Neumann, 1967; Komendantov and Bekmukhametov, 1971; 6.89) and bicyclo[2.1.0]pentanes (Vogelbacher et al., 1984; 6.90).

o 6.89

A 6.90

The nature of the cyclopropane-forming reaction is still controversial in the sense of a differentiation between a two-step cleavage of the two CN bonds and a concerted formation of a biradical in the azo-extrusion part of the reaction (for a review of the older literature, see Mackenzie, 1975, p. 354, and Engel, 1980, p. 118). This reaction does not strictly belong to the scope of this book. Therefore, we will not discuss it further except to refer to an investigation of Reedich and Sheridan (1988) who reported that, in contrast to earlier results (see, e. g., Cichra et al., 1980, and other references there), both thermal and photochemical processes take place by stepwise cleavage in a pair of isomeric dihydro-pyrazoles. More important for the general applicability of the formation of cyclopropane derivatives by azo-extrusion of dihydro-pyrazoles is the relatively old systematic stereochemical investigation of Bergman's group (Clarke et al., 1977). These authors thermolyzed the optically active 3-ethyl-4,5-dihydro-5-methyl-3//-pyrazoles 6.91 and 6.92 in Table 6-3. They observed considerable optical activity in the cyclopropane products, as shown by the different yields of the pairs 6.93/6.94 and 6.95/6.96. Engel (1980) interpreted these results with very small energy differences between competing pathways. For the subject of the present section, we conclude that azo-extrusion of 4,5-dihydro-3/f-pyrazoles is not likely to be a generally recommended method for the synthesis of specific stereoisomers of cyclopropane derivatives. In the majority of cases, metal complex-catalyzed reactions of diazoalkanes with ethenes are probably preferable (see Sect. 8.7). Cyclopropanations by azo-extrusion of dihydro-pyrazoles may be accompanied by rearrangement of substituents. For instance, Hamaguchi and Nagai (1989) showed that, in 4-(arylseleno)- and 4-(arylthio)-4,5-dihydro-pyrazoles, these heteroaryl groups migrate into the 5-position with formation of cyclopropanes or ring opening to ethene derivatives. The present broad interest in the chemistry of cyclopropane derivatives is reflected in the large number of reviews on synthetic methods: we mention only relatively recent publications by Doyle (1986a), Tsuji and Nishida (1987), Maas (1987), and Hel-

232

6 Reactions of Aliphatic Diazo and Diazonium Compounds

Table 6-3. Isomeric l-ethyl-2-methyl-cyclopropanes obtained in the thermolysis of cis- and fraHS-3-ethyl-5-methyl-l-pyrazoline (after Clarke et al., 1977). Products H3C,,/\ ..H H

QjHg

H.,, /\ H3C^^

.C2H5 ^H

H3G,. /\ H

,C2H5 ^H

H... /\

..H

H3C

t^s

6.93

6.94

6.95

6.96

28%

38%

10%

22%

10%

17%

35%

36%

H,.^/X^H ^£\

/ Oft N=N

6.91 H 3 G,/\,.'H

ri \

/ ^-y^s

N=N

6.92

quist (1991 a). These reviews discuss the cycloaddition — azo-extrusion and the metalcomplex catalysis pathway (6-37 A and 6-37 B, respectively). Helquist (1991) gives many examples for thermolytic and photolytic cyclopropanations via dihydropyrazoles (Tables 1 und 2, respectively, pp. 955, 959) and for metal-catalyzed cyclopropanations (Table 3, p. 962). Some photolytic azo-extrusions proceed with excellent yields (see, e.g., Franck-Neumann and Buchecker, 1980). We will return to some cyclopropanations via cycloaddition — azo-extrusion later in this section. Double bonds of benzene and related aromatic compounds do not react with diazoalkanes in 1,3-cycloadditions. The corresponding benzo-annellated dihydropyrazoles such as (1 a,6a)-6,9,9-trimethyl-7,8-diazabicyclo[4.3.0]nona-2,5,7-triene (6.98, R = H) can be synthesized, however, from methyl cyclohexa-l,4-dienecarboxylate (6.97, R = H), as shown by Klarner et al. (1990). The reduction of the ester group to a methyl group was carried out with di-isobutylaluminum hydride (DIBAL-H), esterification of the OH group with methanesulfonyl chloride and reduction with lithium triethyl borohydride. The second double bond was introduced by bromination with Br2 on a polymeric carrier after Bongini et al. (1980). Cycloaddition with 2-diazopropane in ether at - 5 °C and the following steps gave 6.98 in a yield of 58 %. The dihydroarene-diazopropane adduct 6.98 is interesting because of very different product ratios in thermal and photolytic azo-extrusion, as shown in Table 6-4. The different products under varying photolytic conditions are likely to be due to excitation of different chromophores. The absorption at 245 nm (log e = 3.69) is due

"-*» 6.97

6.5 Cycloaddition Reactions with Diazoalkanes in Organic Synthesis

233

Table 6-4. Products in the thermolysis and in various photolyses of the dihydroarene-diazopropane adduct 6.98 (after Klarner et al., 1990).

6.98

Thermolysis in benzene (28-50°C) Photolysis in ether, 254 nm Photolysis in ether, 350 nm Photolysis in benzophenone, 350 nm

• ~

C\ 6.99 94 18 90

cx 06 a ^^\\

^x\

6.100 Product ratio (%)

3 10 10

3

_ 100 72 -

to the 7t -> 7i* transition of the cyclohexa-l,3-diene system, that at 330 nm (log e = 2.54) to the n -* 71* transition of the azo group. The formation of toluene is probably due to a [3 + 2] cycloreversion starting from an excited singlet state. This can be conclued from the observation that toluene is not found in the presence of benzophenone, which is known to quench singlet states. An explanation for the two trimethylcyclohepta-l,3,5-trienes 6.99 and 6.100 was found in the investigation of that cyclohexa-l,4-dienecarboxylate that contains an additional methyl group (6.97, R=CH 3 ) and in which the carboxylic ester group was transformed by deuterium reduction steps resulting in compound 6.101 after cycloaddition with 2-diazopropane. Two pathways are proposed by Klarner, namely for thermolysis and for photolysis with light of wavelength 350 nm, an unusual process in which eight electrons are involved, and for photolysis with more energetic UV light an azo-extrusion of a biradical intermediate (6-40). The second pathway is analogous to diazopropane additions to cyclobutadiene and to cyclooctatetraene, which were also investigated by Klarner's group (Klarner and Glock, 1984; Clock et al., 1985; Klarner et al., 1986).

234

6 Reactions of Aliphatic Diazo and Diazonium Compounds

Very active interest in a new addition reaction of aliphatic diazo compounds started in 1991 when WudPs group reported that diphenyldiazomethane forms diphenylmethanofullerene with buckminsterfullerene (C60; Suzuki et al., 1991). Although this investigation showed that the reaction proceeds via the formation of a dihydro-pyrazole, i.e., in the mode of a 1,3-dipolar cycloaddition followed by an azo-extrusion, we shall discuss the syntheses of methanofullerenes in its entirety in the chapter on carbenes (Sect. 8.4) because Diederich's recent work (see review of Diederich et al., 1994b) shows that the methano bridge can also be obtained from a carbene. The question whether the dihydro-pyrazoles are intermediates or sideequilibrium products (see earlier in this section) is also open for the reaction of C60 with diazoalkanes. Nitriles may be interesting dipolarophiles for cycloadditions with diazoalkanes because 1,2,3-triazoles are the expected products, as shown in 1908 by Peratoner and Azzarello, and by Tamburello and Milazzo (1908). The first-mentioned authors studied the reaction of diazomethane with cyanogen (CN)2, Tamburello and Milazzo that with cyanogen bromide. The products are 5-cyano- and 5-bromotriazole. Cycloaddition of diazomethane gives acceptable yields only if the cyano group is bonded to electron-attracting substituents (review: Benson and Savell, 1950). From the synthetic point of view, 1,2,3-triazoles are more conveniently obtained by another dipolar cycloaddition, namely that of azides with ethenes. Interesting cases for the cycloaddition of diazo compounds to a cyano group are the reactions with (cyano)(trinitro)methane (6-41) investigated by Ladyzhnikova et al. (1988). The cycloaddition of methyl diazoacetate (R = CH3OCO) takes place regiospecifically in good yield (65 %), whereas those with diazomethane and its homologs give mixtures of isomeric triazoles. R R—CHN2

+

NC —C(NO2)3

*~

C(N02)3

N'

\j

(6-41)

H

Investigations of Huisgen et al. (1987 a, 1987 b) demonstrate that, in ethene derivatives with one or more cyano groups in the 1- and 2-positions, competitive cycloadditions at the C = C bond and at the cyano group take place. Aromatic diazonio groups may be mentioned her due to their — at least formal — similarity to nitrile groups. In 1955 Huisgen and Koch investigated the reaction of 4-nitrobenzenediazonium chloride with an excess of diazomethane. They found that diazomethane reacts as a C-nucleophile in an azo coupling reaction (see Zollinger, 1994, Sect. 12.6, p. 339). In ether, 12% of l-(4-nitrophenyl)-l//-tetrazole (6.102) was, however, also found and Reimlinger et al. (1970) isolated l-(l//-pyrazol-5-yl)-l//tetrazole (6.103) in 24% yield from pyrazole-3-diazonium chloride and diazomethane. The low yields indicate clearly that these tetrazole formations are not interesting for synthetic purposes. Are they really concerted dipolar cycloadditions? Bronberger and Huisgen (1984) investigated this question by allowing arenediazonium ions to

6.5 Cycloaddition Reactions with Diazoalkanes in Organic Synthesis

/N

235

/=/N~N

/N~"

OH X X

AT

N

6.102

6.103

react with dipoles that have higher HOMO energy levels and for which a good bond stability is expected for the new o bonds formed with the two diazonio N-atoms. Indeed, they showed that azomethine ylides and thiocarbonyl ylides yielded the expected products of dipolar cycloaddition - but their discussion is outside the scope of this book. Diazoalkanes have the disadvantage, for synthetic purposes, of being toxic and, in many cases, explosive. An important strategy for diazoalkane reactions is the use of diazoalkane precursors. Tosyl hydrazones are often used for such purposes as they easily yield diazoalkanes when an external base is added (see Sects. 3.5.1 and 3.5.2). A further improvement is due to Eschenmoser's group (Felix et al., 1972). This method is based on the work of Huisgen et al. (1966 a), who observed that an aziridin-1-yl imine derivative (6.104), when heated, dissociated into styrene and phenyldiazomethane (6-42). Eschenmoser and coworkers used cis- or trans-l-ammo2,3-diphenyl- and other 1-aminoaziridines for the formation of aziridinyl imines 6.105 with ketones and aldehydes. In apolar and polar organic solvents in the presence of the corresponding reagents these compounds thermally yield the products expected for a reaction with the diazoalkane (for intramolecular cycloadditions, see, for example, Padwa and Ku, 1980 a). A transient aziridinyl imine was used by Schultz and Puig (1985) in the course of their total synthesis (6-43) of (+)-longifolene, a sesquiterpene found in essential oils obtained from the oleo-resins of Pinus longifolia.

(6-42)

C6H5

RCR'=N'

^ 6.105

R = alkyl, R R' = cycloalkyl, R'= alkyl, H

236

6 Reactions of Aliphatic Diazo and Diazonium Compounds H5C6x

COOCH3

1.

^N-NH2

(6-43)

COOCH3

1,3-Dipolar cycloadditions are interesting also for other syntheses of natural products. It is surprising, however, that they have been widely used only since the 1970's, because the primary heterocyclic adducts do not, in most cases, show an obvious resemblance to the structures of natural products (see review of Mulzer, 1991), but also because, before that time, the potential of 1,3-dipolar adducts for secondary ring cleavage and for the formation of other ring systems was not clearly recognized. This is particularly obvious for the introduction of the cyclopropane ring by azo-extrusion of 4,5-dihydro-3/f-pyrazoles, discussed above. An instructive example was provided by Schneider and Goldbach (1980), who obtained the dihydro-pyrazole 6.107 in the reaction of 3-diazoprop-l-ene with (E, ZH,3,5-octatriene by attack on the terminal double bond. Photolysis of 6.107 (>310 nm) at —10 °C provided dictyopterene B (6.109) together with the c/s-isomer 6.108, which gave ectocarpene (6.110) in a Cope rearrangement. Both these natural products are constituents of Pacific brown algae found in the waters around Hawaii. The polycyclic sesquiterpenes are a particular challenge for synthetic organic chemists because they demonstrate the virtuosity of living organisms to build intricate molecules by unusual formation and rearrangements of rings from the common origin of a relatively simple acyclic C15 precursor. Examples are (-)-cyclocopacamphene (6.112) and, earlier in this section, (+)-longifolene (6.106).

6.5 Cycloaddition Reactions with Diazoalkanes in Organic Synthesis

237

hv

(6-44)

Cope

6.110 6.109

For the synthesis of the sequiterpene (- )-cyclocopacamphene (6.112) an elegant application of an intramolecular cycloaddition, forming the annellated pyrazole derivative 6.111 followed by a photolytic azo-extrusion to the cyclopropane, was described by Piers et al. (1971).

(6-45)

6.111

6.112

An instructive example for an application of 1,3-dipolar cycloadditions for the synthesis of model compounds in the reduction of ribonucleotides was provided by Samano and Robins (1992): Treatment of 3',5'-0-(l,l,3,3-tetraisopropyldisiloxanel,3-diyl)-2'-deoxy-2'-methyleneadenosine (6.113, R=1,1,3,3-tetraisopropyldisiloxane1,3-diyl) with excess diazomethane in ether (6-46) gave a mixture of the spiropyrazole derivatives 6.114 (88%) and 6.115 (4%), which can be transformed into the corresponding spirocyclopropanes (6.116). This result is remarkable, because other spirocyclization methods were not successful for this ribonucleotide. The synthesis of optically active cyclopropanes via formation of dihydro-pyrazoles by 1,3-cycloaddition and azo-extrusion has been studied since the late 1950's. Modest success (10% ee) was achieved by cycloaddition of diazoalkanes to acrylic acid, esterified with ( —)-menthol, as studied by Walborsky's group (Impastato et al., 1959). Today, the use of chiral metal complexes as catalysts for the synthesis of chiral

238

6 Reactions of Aliphatic Diazo and Diazonium Compounds B

RO—,

^

B

RO—i

^

B

RO—i

n

B

V-O

(C2H5)20

Q/-V

Orig

RO

6.113

R = 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl B = adenin-9-yl

(6-46)

cyclopropanes from diazo compounds and ethene derivatives is more important (see Sect. 8.8). Mukai's group (Nishizawa et al., 1980), and Padwa and Ku (1980b) discovered that 1-allyl-substituted diazomethanes (6.117) undergo an intramolecular 1,1-cycloaddition to give l,2-diazabicyclo[3.1.0]hex-2-enes 6.118 instead of the expected 1,3-dipolar cycloaddition to 2,3-diazabicyclo[3.1.0]hex-2-enes (6-47). Further work of both groups (see Padwa et al., 1983b; Miyashi et al., 1986) established that these diazoalkenes undergo the 1,1-cycloaddition with complete retention of configuration, but the reaction seems to be limited to a-phenyl-substituted compounds. This formal nitrene-type cycloaddition is reversible.

(6-47)

6.117

6.118

Other types of intramolecular diazoalkane cyclizations were summarized by Tsuge et al. (1989) and Wade (1991). Originally, it was planned to close this chapter with a section on 1,5-dipolar cycloadditions — mainly stimulated by Huisgen's review from 1980. As we could find only few (although interesting) papers on that subject, we add a short summary of such reactions to this section*. In 1935, Adamson and Kenner showed that 3-diazoprop-l-ene (6.119, R = R' = H) slowly cyclizes to give pyrazole (6-48, R7 = H). Closs et al. (1963) found that, besides formation of pyrazole, 1,1-disubstituted 3-diazoprop-l-enes form cyclopropanes via carbenes. Pyrazole formation is an intramolecular 1,3-dipolar cycloaddition; 3-diazopropene is, however, also a 1,5-dipole in the sense of Huisgen's Schemes 6-5 and 6-6, i.e., a compound with a potential diazonio group (6.120; -IsfsN = -6 = a; see discussion by Huisgen, 1980). * The recent reviews on intramolecular cyclizations of diazoalkanes (Tsuge et al., 1989; Wade, 1991) do not include information on 1,5- and 1,7-dipolar cycloadditions.

6.5 Cycloaddition Reactions with Diazoalkanes in Organic Synthesis

R

239

V- NH

6.119

(6-48)

R'

6.120

Pyrazoles were not obtained from 5-diazopenta-l,3-diene derivatives, but 1,2-diazepines (6.121) were (Robertson and Sharp, 1983), i.e., 1,7-cyclization is preferred to the 1,5-reaction (6-49).

(6-49)

If the second double bond after the diazo group is part of a benzene ring, however, such a compound cyclizes by 1,5-closure to give a 3//-pyrazole 6.122 (6-50; Sharp et al., 1975). If the carbon atoms C(l) and C(2) are part of a cyclopentyl ring (6-51), those diazo compounds give the 3/f-l,2-benzodiazepine 6.124 (Stanley et al., 1979). The overall reaction of (6-51) is the replacement of a phenyl H-atom by a diazo group via a reversible Src-electrocyclization to the tricyclic intermediate 6.123 and a 1,5-sigmatropic hydrogen migration. Sharp's group also investigated the corresponding reactions containing thiophene rings (2- and 3-thienyl) instead of phenyl groups (Miller and Sharp, 1984), the formation of l/f-2,3-benzodiazepines from a(2/-alkenylaryl)diazoalkanes (Reid et al., 1973), and the influence of substituents on the phenyl rings in reactions of type (6-51) (Miller et al., 1984). Nitrile imines of type

240

6 Reactions of Aliphatic Diazo and Diazonium Compounds

(6-50)

6.123

6.124

6.125 give l//-l,2-benzodiazepines (6.126, R or R' = H, Garanti and Zecchi, 1977, 1979; see also Padwa and Nahm, 1981), and Sharp's group (Motion et al., 1992) showed that intramolecular cyclizations of diene-conjugated nitrile ylides (6.127) gave analogous products. If R and R' are methyl or phenyl groups, no 1,7-cycloaddition takes place. At the end of this section, it may be said that even though most five- and sixmembered heterocyclic rings can now be readily prepared, the synthesis of sevenmembered rings is not straightforward. 1,7-Cyclizations of conjugated 1,5-dipoles and related reactions may be a subject for more work in the future.

(R'=H)

(6-52) N—N=CR"

6.125

— N=C—C6H5

6.127

6.126

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

7.1 Introduction to Deamination Mechanisms In an earlier review (Zollinger, 1994, Chapt. 8) we explained that the dediazoniation of aromatic diazonium ions to aryl cations and dinitrogen, or to aryl radicals and dinitrogen in the presence of suitable electron donors, is based primarily on the high stability of N2. Analogous aliphatic diazonium ions show similar behavior, but the existence of diazenides (R-Nf) and diazoalkanes also opens the possibility of generating carbanions, e.g., in the Wolff-Kishner reduction and related reactions (see the classic book of Cram, 1965, and the monographs of Staley, 1985, and Buncel and Durst, 1980-1987), and carbenes (see Chapt. 8 of this book). Aromatic diazonium ions contain C — N bonds that are stabilized by n back-donation (see Zollinger, 1994, Sect. 8.4). This effect is not present in most alkanediazonium ions. As a result, they can be observed directly only in special cases (see Sects. 2.1 and 7.3 of this book) and most alkanediazonium ions undergo dediazoniation in very fast reactions, either a bimolecular nucleophilic displacement (an ANDN reaction in the new IUPAC terminology, i.e., addition of a nucleophile and (simultaneous) dissociation of a nucleofuge (IUPAC, 1989a); SN2 after Ingold), a monomolecular dissociation forming a carbocation (DN + AN (the + sign indicates that dissociation and association are two separate steps; SN1 after Ingold), or, in one clearly established case found by Kirmse's group (Bunse et al., 1992; see Sect. 7.3), a dediazoniation taking place homolytically by electron transfer. The primary products of dediazoniations of all types (except ANDN) are extremely reactive and undergo secondary reactions with relatively low activation barriers *. Accordingly, the selectivity of these transient intermediates in consecutive steps is also low. A multitude of final products is formed in most cases. The immediate molecular neighborhood of these species is much more productdetermining than in intermediates with lower reactivity. For example, counterions have a greater influence in consecutive steps than similar ions in the bulk solution. It was shown by isotope labeling that the transient intermediates react preferentially with the water molecules formed during deamination steps rather than with molecules in the bulk water.

* See the discussion of Williams (1985), based on a comparison of secondary deuterium isotope effects in nucleophilic substitutions of R-X, where X stands for various leaving groups, including N2. Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

242

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

As mentioned in Section 1.1, the first diazotization of amines, followed by dediazoniation, was carried out by Piria in 1848, well before Griess discovered and isolated aromatic diazo compounds (1858). Piria added an impure HNO3-HC1 solution to a mixture of asparagine and aspartic acid in water and obtained malic acid (7-1). It was not possible for Piria, however, to realize that the primary reaction products were diazonium ions. Yet, Piria's process was one of the few types of reaction via aliphatic diazonium ions that became important for synthetic purposes, after Ingold's group (Brewster et al., 1950) discovered that a-amino acids undergo clean retentive deamination (see Sect. 7.7). HO2C — CH2—CH—COOH NH2

inH^o)^^ H02C — CH2—CH—COOH /

H2NCO—CH2—CH—COOH

|

-N2

/

(7-1)

OH

NH2

Attention towards an aliphatic diazonium ion as a transient intermediate in nitrosation of alkylamines was subsequently further distracted by investigations of Linnemann and Siersch (1867), who found that in the reaction of propylamine even more propan-2-ol was detected than the propan-1-ol expected. Kinetics of nitrosations of alkylamines were determined as early as 1928 by Taylor, but it was not until Hammett, in his pioneering book on physical organic chemistry (1940, p. 295), that the analogy to the aromatic series was established. He suggested that diazonium ions are also intermediates in the reactions of aliphatic primary amines. Quite early, Ingold and coworkers (Baker et al., 1928) proposed carbocations * as intermediates in these reactions, as the product pattern and the stereochemistry display similarities to those of nucleophilic aliphatic substitutions of molecules with anionic leaving groups like halogenide ions, arenesulfonate ions, etc. (7-2). An important criterion of Ingold for differentiation between the mono- and bimolecular nucleophilic substitution mechanisms was, at that time, the stereochemical evidence available from initial investigations of McKenzie and Richardson (1923), McKenzie and Roger (1924), and McKenzie and Lesslie (1929) for nitrosation of terR_NH2

H20 R+
R— X ' X~ = Hal", ArSO3~ etc.

> FT— OH + H+

(7-2)

^ Alkene + H+ R' = rearranged R

* We use the present terminology for this historical introduction, rather than that of the original publications (carbonium ion; see also remark of Bentley et al., 1988).

7.1 Introduction to Deamination Mechanisms

243

tiary yS-amino alcohols. Such reactions were later investigated in more detail by Ingold's group (Brewster et al, 1950). All these early results were consistent with the DN + AN mechanism. Indeed, Roberts and Mazur (1951 a) found in a comparative study that reactions of aqueous nitrous acid with four substituted l-amino-but-2-enes and 3-amino-but-l-enes yielded the same mixtures of substituted butenols (methylated allylic alcohols) as those of silver ion catalyzed aqueous solvolyses of the corresponding chlorides. This fits the hypothesis that both types of reaction result in the formation of the same carbocation, independent of the route from the amine or from the chloride. This rate-determining part of the reaction is followed by fast product-determining steps. The nitrosation products of these buteneamines are, however, rather exceptional. Far more examples are known in which amine nitrosation gives other compounds or significantly different product ratios than in the solvolysis of alkyl halogenides or arenesulfonates. For instance, Huisgen and Riichardt (1956) found 28% propan-2-ol in the deamination of propylamine in aqueous HC1. In acetic acid, the nitrosation of propylamine yielded more than 30% 1-methylethyl acetate, but the acetolysis of (l-propyl)-4-toluenesulfonate led to only 2.8% of this product. It is a general experience that rearrangements are more frequently observed in nitrosation of alkylamines than in other solvolyses that follow the DN + AN mechanism. This difference is clearly seen in the product analyses of nitrosation reactions of 2-arylalkylamines (7.1) by Cram and McCarty (1957), Coke (1967), and by Kirmse and Feyen (1975). These reactions are characterized by competing 1,2-shifts of all possible groups (Ar, R, and H) attached to the C(/?)-carbon. In the solvolysis of the corresponding sulfonates (7.2), however, only the aryl group migrates (Lancelot et al., 1972; Kirmse and Feyen, 1975). 7.1

X = NH2

7.2

X = OSO2Ar

R, R' = alkyl or H

An elegant comparison was made for the nitrosation of 1,2-dimethylpropylamine (7.3) and the solvolysis of the corresponding 4-toluenesulfonate (7.4). Kirmse and Krause (1975) labeled C(2) with deuterium. With this method, it was possible to show that with the amine an H-shift and a methyl shift take place, whereas the solvolysis of the 4-toluenesulfonate proceeds almost exclusively with an H-shift. These examples on replacement of a primary aliphatic amino group by nucleophiles via nitrosation demonstrate that the mechanism of these reactions is obviously very complex. H3Cx • i /-*.

XCH3

v

73 7.4

x

^

= NH2

244

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

Before we discuss those mechanisms in detail (Sects. 7.3-7.6), we will review in the following section the various methods developed for the formation of alkanediazonium ions, because most of these routes contributed substantially to our understanding of the reaction steps following formation of the alkanediazonium ion. The products obtained are always compounds in which the amino group has been replaced by another nucleophilic group, or in which it is eliminated together with a proton, leading to an alkene. Formation of both types of product may be, and indeed in most cases is, accompanied by rearrangements. The major characteristic of these reactions is the replacement: the traditional name for all processes of this type is deamination. This name was criticized by Collins in 1971 because, in his opinion, this term should be used only for a reaction in which an amino group is replaced by an H-atom. The new IUPAC nomenclature for transformations (IUPAC, 1989 c) eliminated this problem, as the general term 'deamination' concerns replacement of an amino group by any other group, but can be specified by prefixes, e. g., the formation of an alcohol in the aqueous nitrosation of an alkylamine is a hydroxy-de-amination.

7.2 Routes to Alkanediazonium Ions The most important routes to alkanediazonium ions are shown in Scheme 7-3, which is an extended version of a scheme published by Kirmse (1976, 1979). The classical route is the reaction of the alkylamine (7.6) with sodium nitrite and mineral acid (HX) in aqueous solution. The mechanism and the pre-equilibria involved are the same as in the diazotization of aromatic amines, which have been extensively investigated since the work of Hughes, Ingold, and Ridd (1950; see Zollinger, 1994, Chapt. 3). Specific aspects of the nitrosation of alkylamines are discussed in Section 4.1 of this book. An important observation was made by Moss (Moss and Talkowski, 1971; Moss et al., 1973 a) in the nitrosation of 1-methylheptylamine. Above the critical micelle concentration (cmc\ the alkylammonium ions form aggregates in which the hydrophobic alkyl chains are aligned towards the interior of the micelles and the ammonio groups are oriented to the surface. Acid-base equilibrium between amine and ammonium ion is faster than molecular transfer to and from the micelle. Therefore, diazotization also takes place in the micelles, where it is faster than in the bulk solution. Product distribution and stereochemistry are influenced markedly by this micellar effect, as we will see in Section 7.3. The deamination of 1-methylheptylamine is a case of intramolecular micellar catalysis. It was shown later that added micelle-forming compounds not involved in the reaction also influence the rate, the product distribution, and the stereochemistry of deamination. Another important diazotization method is the use of glacial acid for the nitrosation of alkylamines, because of the formation of an ion pair 7.12 between the acetate ion and the diazonium ion. In water the influence of acetate ion is small.

7.2 Routes to Alkanediazonium Ions

245

R2CH-Li+ + N2O 7.8

R2CH—NH2

R2CH—N2—O- ^

+

7.9 ^

R2CH— I/ 7.10XCOR'

Na2Fe(CN)5NO 7.7

R2CH—NH2 + X —NO

^

R2CH—N2—OH ^

[R2CH—N=N X-]

*»

R2CH—fSl^N ^

j-R'COOH

[R2CH—N=N -QOCR'] 7.12

R2CH—N=N

X

HX

7.14

/N—NHAr R2CH—NX 7.16

I hv

(7-3)

R2 N

N—SO^'

7.13

NAr

R2CH—NH—N 7.15

R2CH—NH2

+ ArN2+

Maltz et al. (1971) introduced disodium pentacyano(nitrosyl)ferrate (sodium nitroprusside, 7.7) as nitrosating reagent. This compound has the advantage that it is effective for nitrosations and diazotizations at pH 9-11. This allows the synthesis of alkyldiazenolates (7.9) without deamination by-products, as well as dediazoniations in neutral or weakly alkaline solutions. Nitrosation in aprotic solvents is possible, either with an alkyl nitrite in the presence of an equivalent of acid, or with nitrosyl chloride (Bakke, 1967), or with dinitrogen tetroxide (Wudl and Lee, 1971; Barton and Narang, 1977). Doyle et al. (1978) generated nitrosyl chloride in situ by the reaction of titanium tetrachloride

246

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

with 1-methylbutyl- or tert-butyl nitrite in dimethylformamide and showed that chloro-de-diazoniation becomes the dominant reaction under these conditions. In all these cases, the system is not completely free of water, because in all reactions generating diazonium ions from amines and any nitrosating reagent, one equivalent of water is produced. This problem is not encountered in the thermal rearrangement of 7V-nitroso amides (7.10, R' = alkyl). Aliphatic 7V-nitroso amides were first studied by von Pechmann (1898 a). The rearrangement was originally investigated and elucidated for aromatic 7V-nitroso amides by Huisgen and others (see summary by Zollinger, 1994, Sect. 6.7.5). Huisgen's work clearly showed that, in the rearrangement of the Af-nitroso amides, the (£")-diazo ester (7.11) is formed. lonization of (7.11) leads to an ion pair (7.12), in which the distance between the C-atom adjacent to the diazonio group and the carboxylate group is greater than in the ion pair of the same stoichiometry, but formed by addition of a carboxylic acid to a diazoalkane (7.14). For obvious reasons, the carboxylate anion formed in such a protonation of a diazoalkane in an aprotic solvent is closer to the C-atom to be protonated. We will see in Section 7.3 that this hypothesis is consistent with different product ratios of dediazoniations of diazonium-carboxylate ion pairs originating from these two routes of formation. Instead of Af-nitroso amides (7.10, R' = alkyl or aryl), N-nitroso carbamates (7.10, R' = OR") and 7V-nitroso ureas (7.10, R7 = NHR) can also be used (Kirmse and Wachtershauser, 1967; Hecht and Kozarich, 1973)*. More recently, Kirmse's group (Kirmse and Rode, 1986; Kirmse et al., 1986 a) demonstrated that 7V-nitroso carbamates are preferable to 7V-nitroso amides because of higher yields in the nitrosation step. In the synthesis of 7V-[l-(3-hydroxypropyl)cyclopropyl] acetamide (7.17) Kirmse and Rode (1987 b) found that primary nitrosation takes place at the hydroxy group, and 7V-nitrosation was achieved only after complete O-nitrosation.

"NHCOCH3 7.17

Recently, White et al. (1992 a) showed that 7V-nitroso sulfamates (7.18), a class of compounds related to 7V-nitroso amides, can be used for the generation of diazonium ions in aqueous buffers at pH 2, i. e., in an acidity range where direct nitrosation of aliphatic amines is very slow.

f°

^N\ FT SO3-

K+

7.18

* For some other nitroso compounds and related reagents developed by White for the examination of alkylamines in organic solvents, see White et al., 1992b, refs. 3-7.

7.2 Routes to Alkanediazonium Ions

247

7V-Nitroso amides can also be used for the formation of alkyldiazenolates (7.9) by bases. Alkyldiazenolates can be isolated from aprotic solvents as alkali metal salts, as found by Hantzsch and Lehmann (1902). More modern procedures have been described by Tandy and Jones (1965) and by Moss (1966)*. One obtaines the (Z)-diazenolate, as confirmed by X-ray analysis (Miiller et al., 1963). From Scheme 7-3, one might assume that the route starting with diazenolates will lead to the same products as the nitrosation of alkylamines because the diazenol is common for both pathways. The mechanism of formation of a diazenol from a diazenolate is not, as one might expect, a simple protonation. The mechanism was elucidated only recently by Fishbein's group (Hovinen and Fishbein, 1992; Hovinen et al., 1992). This work may be described as a textbook application of kinetic and related methods. In the first paper, it was shown, on the basis of the pH-rate profile in the range pH 6.0-10.5, that the dediazoniation of (£>methyldiazenolate involves a rate-limiting reaction of a protonated diazenolate. In the light of the well-known complexity of the acid-base equilibria of aryldiazenolates (see Zollinger, 1994, Sect. 5.2), a basic mechanism was presented by keeping the problem of the protonation site of the reacting species open. Only in the second paper was it shown that the overall process is a complex system of three acid-base equilibria, mainly O- and Af-protonation of the (E')-methyldiazenolate and the side-equilibrium of the C-deprotonation of methanediazonium ion to diazomethane, followed by the dediazoniation step (Scheme 7-4). For all equilibrium and rate constants indicated in Scheme 7-4 quantitative experimental results or semiquantitative data from comparisons with related compounds were obtained. The postulated upper limit of the Af/O-protonation

* For a review of the older literature, see Moss (1974). Thallium(i) [(£>methyldiazenolate] was prepared and characterized in detail (including an X-ray structure)-by Keefer et al. (1988 a). ** In contrast to the authors (Hovinen et al., 1992) of this scheme, we represent the equilibrium KG between the diazenol and the 7V-nitroso amine with dotted rather than full arrows, because it is likely that it is not an intramolecular proton rearrangement (see Reynolds and Thomson, 1986). We label the rate constant for the NO-bond heterolysis of the diazenol with k\. This is consistent with the later papers of Fishbein's group, discussed below.

248

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

equilibrium constant Ko was based on an evaluation of the UV spectrum in the region where absorption due to an N-nitroso group is expected (350nm): less than 1.5% of the total protonated diazenolate was in the nitrosoamine form at pH 6.66. The measured kinetic p#a of 8.63 for the decomposition of the diazenolate (Hovinen and Fishbein, 1992) and the lower limit of pKo (< 1.82) allows calculation of the limiting value of pATN to be less than 6.81. The observed decomposition rate constant (&0bs) is independent of pH in the range 4.25-6.53, i.e., at values where the equilibrium concentration of the protonated diazenolate is practically constant. The solvent isotope effect in this pH-independent region (A:H2o/^D2o = 1.49 ± 0.09) is also independent of pH. An isotope effect above unity is expected because of the fractionation factor (0) for the lyoxide ion product of $ = 0.434 (Gold and Grist, 1971; see Chiang et al., 1980). On the basis of the solvent isotope effect and the absence of buffer catalysis loss of the proton does not contribute to the rate-limiting step. The temperature dependence of the observed rate constants leads to the activation energy parameters A//* = 69.6 ± 1.5 kJ mor1 and AS* = -4.5 ± 9.5 J K"1 mol"1. Negative values of AS* are known for DN + AN substitutions. The experimental value of AS* is at most slightly positive. This may be due to solvent electrostriction about the hydroxide ion as leaving group. Electrostriction is also consistent with the solvent isotope effect. There is a large solvent effect in this dediazoniation. The pH-independent rate is 680 times lower in pure ethanol relative to the 96:4 mixture of water and ethanol used for the bulk of the experiments. This result is expected because k\ involves ion pair formation from a neutral reactant. Fishbein and coworkers (Finneman et al., 1993) also investigated kinetics and products of the dediazoniation of two slightly more complex diazenolates, (£>l-methylpropyl- and (jE')-l-phenylethyldiazenolate in aqueous buffer (pH 6-12). Here, the side equilibria of Af-protonation and of C-deprotonation cannot be detected analytically or kinetically. The products are the unrearranged alcohols (53% 2-butanol and 99.1% 1-phenylethanol, respectively) and alkenes (7% but-1-ene + 32% but-2-ene, and 0.9% styrene, respectively). The kinetics are compatible with pK& values of the (E)-diazenols 7.19 (R = 1-methylpropyl: 8.83, 1-phenylethyl: 8.32) and the mechanism (7-5)*.

^

R—N2+

+ "OH

(7-5)

7.19 products

* Fishbein's results with (£")-diazenolates are in apparent conflict with the "ion-triplet" mechanism (7-6), but that mechanism is viable for the more reactive (Z)-diazenolates, for which it was suggested by Moss (1974), see later in this section (Scheme 7-20). See also results of Ho and Fishbein (1994) on a (Z)-diazenolate below.

7.2 Routes to Alkanediazonium Ions

249

products

(7-6)

N=N

R+

~OH -OH

If the diazenoles 7.19 decompose directly to the carbocation R+, N2, and hydroxyl ion, the carbocation character of R in the transition state is expected to be stabilized by mesomeric interaction with the benzene ring (in the case of the 1-phenylethyldiazenolate reaction). The rate constant k\ for that decomposition is, however, smaller by a factor of 16 relative to the reaction of the 2-butyldiazenolate. Therefore, no carbocation character is likely for the transition state of the ratelimiting step in (7-5). The rate constant k\ for (£>2-butyldiazenolate is 37 times greater than that found for (^-methyldiazenolate (Hovinen et al., 1992). This result is consistent with calculations of Ford (1986) and Glaser et al. (1991). Recently, Ho and Fishbein (1994) continued their studies on the decomposition of diazenolates in water with an extensive investigation of the effects of structure on the rates and mechanisms by which primary (£>alkyldiazenolates decompose *. Ho and Fishbein chose the following (^)-diazenolates for this work: butyl-, 2-methoxyethyl-, 2-cyanoethyl-, 2,2,2-trifluoroethyl-l-diazenolate. Results for (£>methyldiazenolate, the subject of the earlier work (see above), were included in the evaluation. The kinetics were measured at 25 °C, ionic strength 1 M (NaClO4) in 96:4 water-propan-2-ol by UV spectrometry in the pH range 5-13. The kinetic results showed that all reactions were cleanly first order, and, with exception of 2,2,2-trifluoroethyldiazenolate, the rates increased by less than 15 % in the presence of varying concentrations (0.02-0.30 M) of eight buffers. Within the pH range 4-10 the observed rate constants (&0bs) followed the rate law (7-7), where Ka is taken as the ionization constant for the diazenol. This rate law corresponds to rate-limiting formation of the diazonium ion from the (£>diazenol, i. e., in principle to the dominant part of Scheme 7-4, which Fishbein's group postulated for the decomposition mechanism of (£>methyldiazenolate (7-5)**.

For (Z)-2,2,2-trifluoroethyldiazenolate the kinetic results are consistent with a rate law in which a term kH[H+] is added to the numerator of (7-7). It corresponds to a second rate-limiting step of the decomposition, namely catalysis of dissociation of the NO bond of the diazenolate assisted by H +. After this rate-limiting step, the 2,2,2-trifluoroethanediazonium ion does not dissociate into the corresponding carbocation and N2, finally producing 2,2,2-trifluoroethanol, but it can lose a proton * This work is a fine example of the recommendation that we made independently and at the same time (see Sect. 7.6). ** The side-equilibria ATN, Ko, and KD were found to be neglible in this investigation.

250

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

to give 2,2,2-trifluorodiazoethane, as previously reported by Dahn and Lenois (1979; see also Loehr et al. , 1988). This mechanism corresponds, therefore, to that pathway in Scheme 7-4 that ends in 2,2,2-trifluorodiazoethane. The decomposition kinetics of this compound were also studied as a function of pH. The competition between that pathway and reaction (7-5) is consistent with hydron exchange experiments in D2O (details in Ho and Fishbein's paper). Ho and Fishbein discussed their kinetic results and the products found in detail. A common mechanism for all (^-diazenolates studied is indicated by the substituent effects. There is a good correlation of the logarithmic rate constants (k{) against Taft's <7* substituent constants (Taft, 1956). The slope of the plot has a value /?* = -4.38 (r2 = 0.977), which indicates a change in charge of «0.9 in going from the ground state of the diazenol to the transition state. The value of p* corresponds to experience with heterolytic bond cleavage leading to aromatic and aliphatic diazonium ions (e. g. , Smith et al. , 1984, 1992; Broxton and McLeish, 1982; Broxton, 1978). Acid catalysis was also found in a few cases (Smith et al., 1986; Broxton and Stray, 1982). In summary, Ho and Fishbein's paper verifies the mechanistic conclusions of their previous investigations on a broader basis *. In addition, it contains the first comparison of the decomposition kinetics of a pair of (Z)- and (£>diazenolates. The isomeric 2,2,2-trifluoroethyldiazenolates were studied comparatively, i. e. , under the same reaction conditions. Ho and Fishbein found that the (Z)-diazenolate follows the same rate law as the (£)-isomer, and that the (Z)-isomer reacts much faster in the acid-independent process (rate constant k\) and in the acid-catalyzed process (&H): #i(Z)/A:i(£) = 2600 and £H(Z/^H(£) = 11000, respectively. Broxton and Stray (1982) reported a roughly comparable ratio for methyl 4-nitrophenyldiazenolate We will discuss the dediazoniation step again in Section 7.3 in relation to the problem of the contribution of nucleophiles to the rate-limiting step under other reaction conditions than those used by Fishbein. The l-alkyl-3-aryltriazenes (7.15; see Scheme 7-3) are easily obtained from aromatic diazonium salts and alkylamines. They exist in a tautomeric equilibrium (see Zollinger, 1994, Sect. 13.4) and, under acid catalysis, they dissociate into both possible combinations of amine and diazonium ion. The aliphatic amine and aromatic diazonium ion will, however, react further with each other, whereas in the combination alkanediazonium ion + aromatic amine the diazonium ion will decompose rapidly into the carbocation and dinitrogen. This system has been used little for mechanistic or preparative deamination studies, obviously because a very complex product pattern is inherent in it. The carbocation may react with the aromatic and the aliphatic amine at the amino group. A modified method was described by Southam and Whiting (1982) using anhydrous acetonitrile as medium at —10 to -5°C**.

* See also the most recent paper of Fishbein's group (Finneman and Fishbein, 1994). ** A water-free system for deamination of l-alkyl-3-aryltriazenes was used first by White and Scherrer (1961).

7.2 Routes to Alkanediazonium Ions

251

The protonation of diazoalkanes (7.14) is also a versatile method for forming alkanediazonium ions and ion pairs. A classical example is Huisgen and Riichardt's investigation of 1-diazopropane (1956). In benzene, the reaction of 1-diazopropane with benzoic acid yields almost exclusively propyl benzoate, whereas in water with perchloric acid a propanol mixture containing 28% propan-2-ol was found. The 1,2-H shift leading to propan-2-ol seems to be minimized by the formation of the diazonium-benzoate ion pair. In water, protonation of the diazoalkane takes place even under neutral or weakly alkaline conditions, but the acid-base equilibrium is strongly on the side of the diazoalkane, as shown by a very slow evolution of N2. Yet, in acid solution the protonation of diazoalkanes is practically irreversible, i. e., dediazoniation is faster than deprotonation, as shown first by Kirmse and Kinkier (1967). In the same decade the influence of substituents at the C(l)-atom was evaluated. As expected, diazoalkanes with an a-carbonyl or an a-sulfonyl group, i.e., diazo ketones (RCO-CHN2), diazo esters (ROOC-CHN2), and diazo sulfones (RSO2-CHN2), are weaker bases than diazoalkanes. Proton addition to these compounds is slower. The stability of the diazonium ions formed is a function of the rate ratio of the deprotonation-dediazoniation of these ions. More O'Ferrall (1967) has reviewed the work with diazocarbonyl compounds. Engberts et al. (1969) investigated the dediazoniation of diazo sulfones. In diazo ketones and esters with an alkyl or aryl group at the C(l)atom (RCO-CR'N2 and ROOC-CR'N 2 , respectively) and in diphenyldiazomethane attack of the acid is so slow that protonation becomes rate-limiting (More O'Ferrall et al., 1964; Dahn et al., 1968; Dahn and Ballenegger, 1969; Albery et al., 1972). Albery and Bell (1961) and Albery et al. (1968) found that the rates of these dediazoniations follow the acidity function HQ as expected, because of the diazo-diazonium pre-equilibrium, but they are also influenced by the nucleophilicity and the concentration of the acid anion (X~ = Cl~ < Br~ < I~). These results are consistent with a steady-state system (7-8). RCO-CHN2 + H+

»

RCO-CH2N2+

+X

" > RCO-CH2X

(7-8)

In my opinion, surprisingly little attention has been paid to the problem of overall yields in deamination and related reactions. For mechanistic evaluations much weight is given, correctly, to product ratios, as they are the best way to elucidate mechanisms after the rate-limiting step. If product ratios are based, however, on a low overall yield, then their use for mechanistic conclusions may be uncertain because secondary products, e. g., polymers were neglected in the evaluation. Overall yields may vary with the method of deamination within a very wide range, as shown by results on deamination of octylamine with various methods, applied under comparable conditions (Table 7-1). Dauben and Willey (1962) found an interesting photochemical method for the generation of alkanediazonium ions in neutral or alkaline aqueous systems. The anions of sulfonyl hydrazones (7.13) eliminate sulfinate ions (R'-SOi~) photochemically and the corresponding diazoalkane is formed. In most cases, the

252

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

Table 7-1. Overall yields in deaminations of 1- and 4-aminooctane by various methods. Method

Solvent

Yield, %

Reference

1 -Aminooctane Nitrosoamide 1 -Alkyl-3-aryltriazene R-NH2 + HNO2 ditto ditto ditto R-NH2 + sodium nitroprusside

AcOH AcOH AcOH AcOH H2O, pH 2 H20, pH 4 and 8 H2O, pH 10

55

Southam and Whiting (1982) ditto ditto Maskill et al. (1965) Monera et al. (1989) ditto ditto

4-Aminooctane Nitrosoamide 1 -Alkyl-3-aryltriazene R-NH2 + HN02 4-Diazooctane

AcOH AcOH AcOH AcOH

96-98

23 25 30 38 61

87 91-100

10 30

Southam and Whiting (1982) ditto ditto ditto

photochemical dediazoniation of the diazoalkane to form a carbene is slower than the protonation to give the alkanediazonium ion. This photolysis can also be used, however, for the 'direct' formation of singlet carbenes or, in the presence of benzophenone as sensitizer, of the corresponding triplet carbene as shown, for example, by a joint investigation by the groups of Kirmse and Houk (Homberger et al., 1989) on 4-toluenesulfonyl hydrazone sodium salts of 2-allylbenzaldehyde, by Kirmse and Mrotzeck's work (1988) on 2-thia-5- and -6-norbornanediazonium ions and their SS-dioxides, and by Bentley's publication in collaboration with Kirmse (Bentley et al., 1988) on the photolysis of the tricyclo[3.3.0.02'7]octan-6-one 4-toluenesulfonyl hydrazone (7.20; see also Sect. 7.5). Photolyses of 4-toluenesulfonyl hydrazones were reviewed by Ando (1978, p. 362) and Padwa and Ku (1980 a).

N—NHTs 7.20

Short reference will be made to the decomposition of benzylazoxy-4-toluenesulfonate (7.21) studied by Maskill's group (Maskill, 1980; Maskill and Jencks, 1984,1987; Conner and Maskill, 1988; Gordon and Maskill, 1989, and further papers mentioned there). As shown in (7-9), this reaction also leads to solvolysis products of carbocations, but with nitrous oxide as a leaving group rather than an N2 molecule. The intermediacy of an alkoxydiazonium ion (7.22) is postulated on the observation that considerable amounts of benzyl thiocyanate (7.23) and some benzaldehyde

7.3 Deamination Mechanisms of Open-Chain Amines: Substitution Products . ,/ R- N 1

CF3CH2OH / H2O 1 : 1 — ^

253

[R+ N20 -OTs]

NaSCN

\ 53%

R

=

(v

/>—CH2

RO—N2+

N20

7.22

ROM + ROCH2CF3

(7-9)

and by-products ^^HgO, buffer

C6H5CHO + N2

7.24

(7.24) are formed*. Similar experiments were also conducted by Maskill and coworkers with 2-adamantyl- and with phenylazoxytoluenesulfonate. Although this reaction does not lead to an alkanediazonium ion, it is obvious that it is another method that is closely related to the deamination pathways discussed in this section. The azoxytoluenesulfonate method is related to the use of Nnitroamides as a source for carbocations because the leaving group is also nitrous oxide (7-10). The 7V-nitroamide decomposition was used extensively by White and coworkers in the 1960's and 1970's (see White and Grisley, 1961; White et al., 1973; White and Field, 1975, and literature cited there). JV-Nitro carbamates (7.25, R' = OR") can also be used. Baumgarten and Curtis (1982) have reviewed deamination methods in general, including those via nitrosations.

R—NH—COR7

>- R—N—C —R'

—*—^

R+ + N2O + ~OOCR' (7-10) RO—C —R'

O

7.3 Deamination Mechanisms of Open-Chain Amines: Substitution Products We have reviewed the early history of primary aliphatic amine deaminations up to the 1950's in Section 7.1. The mechanisms that were postulated and evaluated until the late 1960's or mid-1970's have been discussed by various authors (White and * For some critical remarks to this reaction scheme see White et al. (1992 b).

254

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

Woodcock, 1968; Collins, 1971; Moss, 1971, 1974; Kirmse, 1976, 1979; Whittaker, 1978, p. 617), but surprisingly only rarely later (briefly by Laali and Olah, 1985, more extensively by Manuilov and Barkhash, 1990). March reviews extensively other aliphatic nucleophilic substitutions in his book Advanced Organic Chemistry (1992), but he makes little reference to deamination mechanisms. We want to discuss these mechanisms on the basis of the classical but up-dated Scheme 7-11, proposed in a slightly different form by Streitwieser (1957), and regarded at the level of knowledge gained up to the 1990's. We classify our discussion into amines, in this section open-chain amines without rearrangement, and subsequently eliminations and rearrangements of open-chain amines (Sect. 7.4), and mono-, bi- and tricyclic compounds with amino groups (Sect. 7.5).

H+>

2^

A

A

o

displacement by solvent with inversion

solvolysis, elimination etc.

elimination

(7-11) solvolysis, elimination etc.

solvolysis, elimination etc.

trapping with radical scavengers

We begin the discussion on deaminations of open-chain amines with the only case in which the rate-limiting step is the formation of the alkanediazonium ion. This brings us to the evaluation of compounds in which the amino group is attached to C(l) of an «-alkane. Two relatively recent investigations of Fishbein's and Kirmse's groups (Hovinen and Fishbein, 1992; Brosch and Kirmse, 1991), using diazotization kinetics of methylamine and the deamination products of two stereochemically pure l-amino[l-2H]alkanes, respectively, elucidated clearly fundamental problems of

7.3 Deamination Mechanisms of Open-Chain Amines: Substitution Products

255

deamination mechanisms. Their results are landmarks for the understanding of deaminations. They will be guidelines for our further discussion in this and the following sections. Subsequently, we will discuss in this section compounds in which the amino group is bonded to the central C-atom of a secondary or a tertiary alkyl group (i.e., RR / CH-NH 2 and RR'R"C-NH2, respectively). It is not meaningful, however, to follow this sequence too rigidly because comparisons of results with, for example, amines containing primary and secondary alkyl groups, are important for mechanistic considerations. For the same reason, some comparative data obtained for cyclic compounds are included briefly in this section. Recent evidence for deamination initiated by electron transfer, i. e. , a homolytic mechanism (pathway (f) in Scheme 7-11) will be reviewed at the end of this section. Bis(trifluoromethyl)diazomethane (7.26) is protonated in fluorosulfonic acid and the equilibrium is essentially on the side of the corresponding diazonium ion (7.27) at -70°C (Mohrig et al., 1974). As mentioned in Section 2.1, this was the first reasonably stable alkanediazonium ion observed. At -5 to +5°C, it undergoes slow dediazoniation (7-12). The kinetics of this reaction were found to be of first-order both in the concentration of diazonium ion and of the nucleophile. This is consistent with an ANDN-type displacement of the diazonio group by the fluorosulfonate anion (k\ > k_\\ k_\ < k2), but not with unimolecular dediazoniation of the diazonium ion, followed by reaction of the alkyl cation with fluorosulfonate (DN + AN, IUPAC, 1989 a). FS03H

7.26

L > fr-i

(CF3)2CHN2+ + -QSO2F

7.27 (7-12)

(CF3)2CH—OSO2F + N2

Basically, the dediazoniation of diazoacetate (7.28) and diazoacetone (7.29) follows the same mechanism. The intermediate diazonium ions are not stable, but are steady state intermediates (k\ < /r_i; k_\ > k2). McCauley and King (1952), Albery and Bell (1961), and Albery et al. (1968) found that the measured overall rate constants k of these dediazoniations are proportional to the acid strength in aqueous solution (Hammett acidity function h0) reflecting the expected influence of acid on k\, but the constants k also increase linearly with addition of salts of the acid used. The influence of these acid anions is a function of their nucleophilicity (Cl~ < Br- < I-)* RO—CO—CHN2 7.28

H3C—CO—CHN2 7.29

* There is also, of course, a term for water as a nucleophile.

256

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

Diazomethane derivatives substituted by two aromatic rings (e. g. , diphenyldiazomethane) or fused aromatic systems (diazofluorene, diazoacenaphthenone) decompose analogously, but with rate-limiting protonation (as shown by general acid catalysis; see, e.g., More O'Ferrall et al., 1964). The recent work on the dediazoniation of the (jE')-methyldiazenolate (Hovinen and Fishbein, 1992; Hovinen et al., 1992; Ho and Fishbein, 1994) demonstrates that the ANDN mechanism also exists in this case. The evidence given by Fishbein and coworkers for the mechanism of (J£t)-methyldiazenolate protonation to methyldiazenol was already discussed in detail in the preceding section. In the context of Scheme 7-1 evidence for a rate-limiting ANDN mechanism is provided by decomposition experiments in the presence of a large excess of sodium iodide applied to experiments performed in D2O. Under these conditions, 80% of the yield is methyl iodide. The observed rate is, however, only 1.25 times higher. With other good-to-strong nucleophiles in concentrations up to 1 M («-propylamine, methoxylamine, morpholinoethanesulfonate, hydrazine) no dependence on nucleophile concentration was found. Diazomethane is not on the direct pathway to methyl cation and methanol, as shown by deuterium labeling (see, however, later in this section, experiments with the 7V-nitroso acetamide of [l-2H]butylamine). We emphasize that the results with (J£')-methyldiazenolate as described above are completely different from those with (Z)-diazenolate. They will be discussed later in this section. As the investigations of Fishbein' s group were made in the physiological pH range, they are important for the mechanistic investigation of carcinogenic nitroso compounds, which are potential sources of alkylating reagents (see Galtress et al., 1992, reviewed in Sect. 4.2). It would be welcome if Fishbein' s work on the early steps of the methylamine deamination would be continued by a stereochemical investigation of the dediazoniation proper by use of chiral methylamine, i. e. , the compound in which the C-atom is stereospecifically substituted by the three isotopes of hydrogen, i. e. , protium, deuterium, and tritium. The first compounds with a chiral methyl group were (R)- and (5)-[2-2H,2-3H]acetic acid, synthesized by the groups of Cornforth and Arigoni in 1969 (Cornforth et al., and Liithy et al., respectively)*. As far as we are aware, there is only one investigation on a deamination of a chiral methylamine, namely Gautier's (1980) investigation of the pyrolysis of (R)- and (5)7V-[2H, 3H]methyl-Af-nitroso-4-toluenesulfonamide (7.30) to give methyl 4-toluenesulfonate (7-13). The reaction was conducted in chlorobenzene at 95 °C (12 h, yield T

I

7C-N-S02C7H7

T

— i— ^

\

N2 +

C-0-S02C7H7

(7-13)

H

7.30

H

* Compounds with chiral methyl groups are used mainly in bioorganic research (review: Floss et al., 1985).

7.3 Deamination Mechanisms of Open-Chain Amines: Substitution Products

257

65 %). Analysis of the product demonstrated that the methyl ester was formed by inversion of configuration, i. e., the stereochemistry expected for an ANDN substitution (pathway (a) in Scheme 7-11). Gautier's result is in contrast to that found by White et al. (1981) in the deamination of A^-(l-methylpropyl)-7V-nitroso-4-toluenesulfonamide, i.e., an amide with a "classical" chiral C-atom*. At lower temperature (40°C) the product isolated in low yield (9-19%, in acetonitrile, pentane and CH2C12) showed retention of configuration. We will return to investigations with chiral compounds below. The investigations with diazenolates were made in water and ethanol. Diazenolates can also be decomposed, however, in aprotic solvents by addition of one equivalent of an acid HX. An ion pair is formed that contains one water molecule. Deaminations by this route have been investigated mainly by Moss (review: Moss, 1974). A completely different route to diazenolates is the alkylation of nitrous oxide (N2O) by lithium salts of alkyl anions (Beringer et al., 1953; Meier and Frank, 1956). This method cannot be recommended, however, because of the formation of by-products. Diazenolates can be esterified by alkyl- and arylcarbonyl chlorides (White et al., 1972, 1992b). The second major mechanistic criterion besides kinetics is the configuration of the products: racemization is expected for a DN + AN mechanism, inversion of configuration for an ANDN mechanism. For obvious reasons, this criterion cannot be applied to systems in which the alkanediazonium ion is formed in a protonation equilibrium from a diazoalkane because that leads to racemates (see, for a classical case, Streitwieser and Schaeffer, 1957 b). The configuration of products provides interesting information, however, for deamination reactions of amines in which the amino group is bound to the chiral C-atom of a secondary or tertiary alkyl group. Considerable methodological progress was achieved when, with the greater availability of hydrogen isotopes in the 1940's and 1950's, it became clear that the C(l)-atom in a [l-2H]alkylamine (R-CHD-NH 2 ) is chiral. This result opened the possibility of investigating the stereochemistry of deamination of primary alkylamines. Streitwieser and Schaeffer (1956) synthesized amino [l-2H]butane and investigated (1957 a) the configuration of the acetoxy-de-amination product [1-2H] butyl acetate in acetic acid as solvent by polarimetry, the only tool available at that time. The configuration of this product was found to be 69 ± 79/o inverted (31 ± 1% racemized). The authors concluded that it was the result of two competitive reactions, namely (1) an ANDN-type substitution, yielding the inverted stereoisomer (reaction (a) in Scheme 7-11), and (2) primary formation of free butyl cations, leading to racemization (reaction (b)). In the same paper, the authors also reported an investigation into the analogous reaction with 2-methyl[l-2H]propylamine and found 28 % inversion of configuration (error limits not given).

* The deamination of 1-methylpropylamine is, however, with respect to chirality, not comparable to that of labeled methylamine, because in 1-methylpropylamine the amino group is at a secondary C-atom, where retention of configuration is characteristic.

258

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

This paper became exceedingly influential on a large number of publications of many authors during the following decades. It was probably the most frequently cited paper on deamination for a considerable time. The hypothesis that this reaction is based on (at least) two competitive mechanisms was a reasonable basis to explain the numerous products in the deamination of butylamine, which had already been analyzed by Whitmore and Langlois a quarter of a century earlier (1932) to be (in aqueous HC1) 25% butan-1-ol, 13% butan-2-ol, 5% 1-chlorobutane, 3% 2-chlorobutane, 36% butenes, and a trace of butyl nitrite*. It became customary for many authors to use the designations Ar s , kc, and k&, as given in Scheme 7-14, for the three main pathways for the solvolytic substitution of diazonio groups, namely the direct displacement (ANDN; &s), the formation of a carbocation (kc), and the anchimeric assistance (£A) by suitable groups R.

(7-14) <

It is not an exaggeration to state that Brosch and Kirmse's contribution to the same reaction, but 34 years later (1991), was a sensation. At that time, theory and experiment (Ford and Scribner, 1983) indicated that the dediazoniation of 1-alkanediazonium ions is endothermic in the gas phase. Therefore, Brosch and Kirmse considered it as rather unlikely that racemates are really formed in such significant amounts as found by Streitwieser and Schaeffer for [1-2H] butylamine (31%) and 2-methyl[l-2H]propylamine (72%). Brosch and Kirmse, therefore, reinvestigated these two deaminations using the shift reagent [Eu(dcm)3][tris(rf^-dicampholylmethanato)europium(m)] (see Shapiro et al., 1983, and others), by which the 2H NMR spectra of the complexes derived from this chiral reagent and products exhibited well-resolved peaks for the

* Products of elimination and rearrangements will be discussed in Sect. 7.4. ** In reaction schemes and equations in which we do not specify the nucleophilic reagent, we write Nu~ with the meaning of including both anionic and neutral nucleophiles (e.g., solvent molecules).

7.3 Deamination Mechanisms of Open-Chain Amines: Substitution Products

259

diastereomer deuterons. The result was indeed that both amines were deaminated in acetic acid and in water with practically complete (±2%) inversion of configuration!* Later, the same authors (1993) found essentially the same result for the deamination of [l-2H]octylamine, but only in submicellar aqueous solution and in acetic acid (see later in this section). Primary cations (pathway kc in Scheme 7-14) are not, therefore, within experimental error, involved in these deaminations. The additional result that the inversion of configuration was complete not only in acetic acid (Streitwieser's experiments), but also in water renders it extremely unlikely that carbocation-counterion pairs must be considered for the stereochemistry of these two reactions. In a second paper, Streitwieser and Schaeffer (1957 b) used the same sample of [l-2H]butylamine for the JV-nitroso amide method of deamination in acetic acid and found complete racemization. They rationalized this result by assuming the formation of 1-diazobutane as an intermediate, as shown in (7-15). Although a repetition of this process, but using the 2H NMR method for stereochemical analysis, is not likely to give a substantially different result, it would be welcome for clarification. H(D)

^

(D)H

N=N

+ (D)HOOC—CH3

(7-15)

The results of Brosch and Kirmse undoubtedly have had a broad influence on mechanistic interpretations of the stereochemistry of deaminations. An example is the investigation of Monera et al. (1989) on the decomposition products of octanediazonium ion (7.31) in aqueous buffer solutions at pH 2, 4, 8, and 10. In accord with Streitwieser (1957) and Maskill et al. (1965), they assumed that the bimolecular displacement of the diazonio group by water starts from the conformation of 7.31 that is likely to be the most stable. As the diazonio group at C(l) and the alkyl chain (R) at C(2) are in antiperiplanar conformation in 7.31 A, an ANDN-like displacement, as found by Brosch and Kirmse, is, in the opinion of the present author, more likely than a displacement from the two other conformations (7.31 B and 7.31 C)**.

* From the point of view of the history and the philosophy of scientific discoveries, it is interesting to compare the sequence of papers Streitwieser-Schaeffer (1956) -> Ford-Scribner (1983) -> Brosch-Kirmse (1991) with that of the dediazoniation of aromatic diazonium ions. The history of mechanistic elucidation in the aliphatic series was strictly logical, whereas that of the aromatic compounds was characterized by a psychological barrier of breaking the paradigm of the (apparent) inertness of N2 reacting with a simple organic species, the phenyl cation (for a review of that case, based on the theories of Popper and Kuhn, see Zollinger, 1994, Chapt. 9). ** For further discussion of the elimination and rearrangements of 7.31A-7.31C, see Sect. 7.4.

260

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

(7-16)

There is no doubt that conformational control is an important factor for the stereochemistry of deamination pathways. The configuration of the products depends, in principle, on the relative stability of the various conformers of the reactants (amines) and intermediates (e. g., diazonium ions), but also on the activation barriers between the various conformers. Conformational control of stereochemistry is dominant only if the activation energies of conformational changes are greater than those of the product-forming steps. The activation energies of conformational changes are small in open-chain CC bonds (ca. 10-15 kJ mol"1) so that the relative population of the conformers is not usually product-determining. Alicyclic, particularly polycyclic, amines are more rigid with respect to conformation equilibria; therefore, we will discuss the influence of conformation in more detail later (Sect. 7.4). Brosch and Kirmse's results (1991) also have some implications on reactions involving ion-pair intermediates. We shall return to those consequences after a discussion of general aspects of ion pairs as transient intermediates in deaminations. Among the investigations in which kinetic measurements and product analysis played a major role for the development of hypotheses on the structure of various ion pairs, those based on deaminations of chiral 1-phenylethylamine by various methods and those starting with alkyldiazenolates are, in our opinion, a good introduction to the complexity of ion-pair intermediates. A thorough investigation of 1-phenylethylamine deaminations by various routes was published by White et al. (1992 b). White's group investigated five processes that all start initially from 1-phenylethylamine. In three of these, dinitrogen is formed as a leaving group and, in the other two, nitrous oxide is formed (Table 7-2). The other leaving group in all these reactions is naphthalene-2-carboxylate ion (for reaction 1 and 5 benzoate was also tested). As indicated in Table 7-2, the carbonyl O-atom of the naphthalene-2-carboxylate group was labeled with 18O, and 18O distribution was determined for the naphthoate formed*. All reactions were carried out in dioxane, in part also in dichloromethane and in acetic acid. The results in Table 7-2 clearly show that, in dioxane and in dichloromethane, all five reactions result in amounts of retention of configuration that are not * Part of the data are taken from White and Aufdermarsh (1961).

7.3 Deamination Mechanisms of Open-Chain Amines: Substitution Products

261

Table 7-2. Deamination intermediates and products of 1-amino-l-phenylethane derivatives in dioxane at 25°C after White et al. (1992 b), R = 2-naphthyl. Reaction

Reagent

Intermediate

Product and O distribution

i«0

1

J>

HA, f H^-^ H

HA,

/*

/ 54.55 %

\\

xN-o"Si

— H^ C~N

HA

— HC-C-° 3

H

j

% overall retention of configuration in ester dioxane dichloro- acetic methane acid

18

18

0

/

I"

R +N

*

«X

73

~76

67

~68

81

~ 82

^wo

o HA^

X N—OT

HA,

X N—O^

"R X

*"

"H'

«

HA^

Jl

V °n/c^R

H3C'yC H

R

+

HA, ^ ^N -O3 H/"

, RC PP'SOTI + oa

o-

72-74

69

S

II

CV

HA, ^-O^ H-)C"y 3^

N

+ N2

57%-0

18Q

f

K+

X-Q

R

"^

J^

H3C'y y H

y

71-75

\ 43 % 18O 57 % 18O

HA,

H

I8

S

HA, f=o'8o

o

68_69

6g

significantly different from each other (68-76%), but are slightly lower than those found in acetic acid, i. e., in a solvent which is more strongly interacting with reactants and intermediates *. 18O Scrambling also gave results that are very similar for the three reactions for which this criterion was investigated. Unfortunately, the authors provide little specific information on other products than the naphthoates mentioned in Table 7-2. It is stated only that styrene is formed, obviously a product of proton elimination (reaction (c) in Scheme 7-11). White et al. (1992 b) rationalized their and preceding results by a scheme that we reproduce here in a slightly modified version (Scheme 7-17). It is characterized, first of all, by the concept of inert molecule-separated ion pairs, used earlier by White in a slightly different form ("vibrationally excited ion pair") (see, e.g., White et al., 1967). It was extensively used by Moss and Landon (1970), by Moss (1974), and by Whiting and coworkers (Maskill and Whiting, 1976; Whiting, 1982; see also * Earlier results of Baron and Kirmse (1976) demonstrated that in methanolysis of 1-phenylethane-l-diazonium ion the amount of retention of configuration is practically independent of type and concentration of added base (80-82%), but not in chiral phenyl[2H]methanediazonium ion (7.32).

262

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

7.32

Sect. 7.5). These inert molecules* are N2 and N2O in the five reactions of Table 7-2. Their occurrence explains the fact, at least in part, that, in deaminations of alkylamines, the product ratios are often distinctly different from those of alkyl chlorides (etc.) and 4-toluenesulfonates (see Sect. 7.1). In the proposed inert molecule-separated ion pair, the distance carbocation-N2-counter ion is not changed as illustrated by 7.33, 7.34 and 7.35 in Scheme 7-17, but structures 7.34 and 7.35 are characterized by rotation of the carbocation relative to the counterion. Escape of the inert molecule leads to the intimate ion pairs 7.36 and 7.37. The formation of solvent-derived products becomes dominant only if the carbocation and the solvent have a relatively high reactivity. The distribution of 18O in the products is reasonably close to 50:50 in order to conclude that rotation of the carboxylate is almost free in the inert molecular-separate ion pair stage. Based on Brosch and Kirmse's result (1991) that from optically active [l-2H]butylamine completely inverted [l-2H]butan-l-ol was obtained, we added this type of bimolecular displacement to White's Scheme 7-17 (pathway ANDN to 7.38). As shown later (Sect. 7.6), it is not, however, unambiguous to assume that this reaction indeed follows an ANDN mechanism. The work of White's group is related in some part to investigations made by Collins and coworkers more than 30 years ago (Collins and Christie, 1960; Collins et al., 1961; see also Collins' review, 1971). They investigated the thermal decomposition products of A^-nitroso-7V-(l,2,2-triphenyl[l-14C]ethyl[2-14C]acetamide (7.39) in unlabeled acetic acid (7-18). The mixture is characterized by the ester of retained configuration in which the acetyl group was still labeled (7.40), and the inverted ester from which the label had been lost, i. e., it was formed by reaction with the solvent (7.41). The reader who is not well acquainted with the extensive and controversial literature of deamination mechanisms of the last five decades may have the impression from our relatively detailed review of White et al.'s recent paper and of the related work of Collins' group that the dominant role of ion pairing in deaminations was not clearly recognized earlier. This is by no means the case. The paper of White's group (1992 b) was chosen for this discussion because it combines and expands previous partial results with 1-phenylethylamine derivatives for which mechanistic conclusions are not disguised by a multitude of products as they are illustrated in the introductory Scheme 7-1. This term is not strictly correct, as neither N2 nor N2O is completely inert.

7.3 Deamination Mechanisms of Open-Chain Amines: Substitution Products

263

HS-OC+O CK: b

1

c"

7.33

( retention: \ \ major path y

(7-17) - N2, - H+

Vs b

'

'

x

I \

inversion: minor path

I /

7.38

Actually, the first experimental evidence for ion pairs as intermediates in deamination mechanisms was obtained very early by Ott (1931). He observed that the reaction of optically active 1-phenylethylamine with nitrous acid in acetic acid gave 1-phenylethanol acetate with partial retention of configuration, whereas the analogous reaction in water yielded the alcohol with partial inversion of configuration. Ion-pair intermediates have been postulated specifically, at least since the 1950's, e.g., by Huisgen in his pioneering work on the rearrangement of 7V-nitroso amides (Huisgen, 1951 a, 1955, and other early papers of his group; see also work of Cohen, e.g., Cohen and Jankowski, 1964), by White (1955) on the influence of solvent polarity, and by More OTerrall, who realized that diphenyldiazomethane in ethanolic solutions of carboxylic acids gave much higher proportions of benzhydryl esters than expected based on the relatively low nucleophilicity of free carboxylate ions (review: More OTerrall, 1967).

264

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates 14

C H3

14

ONx /CO-"CH3

14

in 12CH3COOH

N2 (7-18) H5C6

7.39

12

CH3COO~

O

X

' N 2

-14CH3coo-

H

14

V

CH3

o/

o

H5C6

O

7.40

7.41

The inert molecule-separated ion pair formation in Scheme 7-17 may be regarded as a two-fold dissociation of R — N2 — OCOR', giving successively the diazonium ion-counterion pair (R —N/ ~OCOR') and the separated ion pair (R+ N2 "OCOR'), or it may be a concerted decomposition, leading directly to (R+ N2 "OCOR'). Southam and Whiting (1982) presented arguments for the second alternative in deaminations of octane-4-amine based on internal-external product ratios for 7V-nitroso butanamide solvolyses in acetic acid. That explanation is, however, falsified by the results of Fishbein's group discussed earlier in this section*. As mentioned earlier in this section, the term inert molecule-separated ion pair is not strictly correct. The complexity of such intermediates becomes even more evident if a carboxylic acid (HX, X = R'COO" in Scheme 7-21, later in this section) is used as reagent in alcohols (X = "OR) or even in water (X = ~OH). The latter type of deamination was introduced by Moss et al. (1970, 1971; see also Moss and Lane, 1967) in an elegant study of the hydrolysis of optically active octyl2-diazenolate (containing unlabeled oxygen) in ether with H218O. The inverted octan-2-ol contained more 18O than the octan-2-ol with retained configuration (7-19). OH

34%18O

72%18O

* For an earlier review on concerted versus two-step dediazoniations of diazo compounds R-N 2 -X, see Vaughan and Stevens (1978).

7.3 Deamination Mechanisms of Open-Chain Amines: Substitution Products

265

Experiments conducted with optically active (Z)-l-phenylethyldiazenolate in alcohol by Moss and Landon (1970) and by Kirmse and Arold (1970) gave results that are analogous to those using octyl-2-diazenolate with H218O. The compound 7.42 is formed with predominant retention of configuration and the ether 7.43 with high inversion. Other examples with similar results were provided by the ammonolysis and the hydrazinolysis of (Z)-l-phenylethyldiazenolate (Moss et al., 1973b; Moss and Powell, 1975, respectively) as well as in the ethanolysis and thioethanolysis of 2-octyldiazenolate (Moss and Lane, 1967; Moss et al., 1970; Moss and Grover, 1976). in ROM

/

N=N

\

, ,

-

Rcr

(7-20)

-.III^LJ

RO RO

^

i

-N2

OH

H 7.42

OR

CH3

7.43

Mechanism 7-20 clearly demonstrates that the dediazoniation starting with (Z)-diazenolate is completely different from the dediazoniation of (£>methyldiazenolate (Scheme 7-4, in the previous section), investigated by Fishbein's group (Hovinen et al., 1992). The different mechanisms of the (Z)- and (£>systems are a consequence of the much higher stability of (£)-diazenolates. Gold et al. (1984) were also able to demonstrate that, starting from propyl- and (5)-l-phenylethyl[16O]diazenolates (7.44), in dediazoniation in H218O (= HX), the "internal" water molecule (H216O) is an effective competitor for the "external" bulk water (H218O), when an amine R-NH 2 with R = secondary alkyl group was used, but not when R is a primary alkyl group. This difference between diazenolates with primary and secondary alkyl groups provides evidence for the conclusion of

266

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

Moss (1974) that R —N 2 + X~ is involved when R is a primary alkyl group, but R + N 2 X~ when R is a secondary alky group. The differentiation was found to be optimal under alkaline conditions, but equilibration between internal and external water dominated in neutral solution. Scheme 7-21 (slightly modified from Whittaker 1978, p. 621, and from Banert et al., 1986) shows that the three intermediate complexes contain, besides the cation and the nitrogen molecule, either the internal or the external anion (7.45 and 7.47, respectively) and, in 7.46 an H216O water molecule and the external anion. R—NH2 + HNO2 R—OH -N2

R— N2—O~ [ R ~ N2+ Jsolv(H 2 0)

7.44 + HX + HX

R-N2-OH

i

|R-N2+

^

\^ X-|

-H20 2

-+

T

1

[R-N2+ X'J

(7-21)

R

f

-owl

N2 J

[

R+

7.45 ~ N?

H20

N2

*-

1

I"

Y_

J

L

N2

R+

7.46 *

^/-HX

7.47

-H 2 0'

R—OH

R—X

HX = H218O (Gold etal., 1984) = R'COOH (Banertetal., 1986)

Kirmse and coworkers (Kirmse and Siegfried, 1989; Banert et al., 1986) intensively investigated the reactions shown in Scheme 7-21; first, by conducting the reactions with six structurally different amines, and second, by using for each of these deaminations 3-4 solvents of decreasing polarity (water, acetic, 3,3-dimethylbutyric, and 2-ethylhexanoic acid), as shown by their ^(30) solvent parameters (see Reichardt, 1988). Water has a much higher nucleophilicity, however, than the carboxylic acids and, therefore, the results in water are not directly comparable with those for the other three solvents. Decreasing polarity of these carboxylic acids increases the extent of front-side attack of the internal nucleophile H2O via collapse of the

7.3 Deamination Mechanisms of Open-Chain Amines: Substitution Products

267

ion pair 7.46 (for the configuration of R —OH, see below). The reactions of the external nucleophile X~ yield increasing amounts of products R —X with inverted configuration in solvents of lower polarity. It is known that the structure of the amines is the major factor determining the configuration of the products in aqueous deaminations. Kirmse's work included the following amines: ejco-norbornyl-2-amine (7.48), trans-4-(tert-butyl)cyclohexylamine (7.49), (+)-(S)-l-methylpropylamine (7.50), (2#,3S)-l,2-dimethylbutylamine (7.51), cyclopropylamine (7.52) and its 2,2,3-trideuterated derivative (7.53), 4,4-dimethyladamantyl-2-amine (7.54) and its a«fr'-isomer*. JH LJ r» M U

-S^iCHg

5 2

NH2 7.48

/—

7.49

\ X NH2

^ 7.50

NHo

7.52

The aqueous deamination results demonstrate that two types of decomposition can be differentiated (see Scheme 7-14): 1) Competing hydrolysis via attack of H2O on the carbocation (kc) and concerted attack of water on the diazonium ion (&s) result in partial inversion of configuration, if steric hindrance and neighboring group participation can be neglected (e.g., for 7.50). 2) Partial retention of configuration is found for steric congestion (e. g., 7.51) and alkyl bridging (7.48, syn- and anti- 7.54) (via pathways kc and £A, respectively). The stereochemistry of alcohol formation in water and in carboxylic acids is strongly influenced by the substrates of group (1), but little by those of group (2). We will discuss the case of cyclopropylamine later in another context in this and in the following section. There are two methods by which the distance between ions in ion-pair intermediates can be varied. Both were developed by the group of Moss using diazenolates as precursors to diazonium ions and carbocations**. The first method * The first two compounds and their deaminations were described by Kirmse and Siegfried (1983), 1,2-dimethylbutylamine in water by Kirmse and Prolingheuer (1980), and the others by Banert et al. (1986). ** See also White et al. (1972).

268

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

is based on a comparison of the (Z)- and (£>diazenolates in diazo decompositions. (Z)-Diazenolates are formed by deacylation of Af-nitroso amide under basic conditions. The (£T)-isomer can be obtained from alkyl hydrazines, 1-methylbutyl nitrite, and base (Thiele, 1910). When the (Z)- and the (£>isomers of optically active 1-phenylethyldiazenolate are alkylated with triethyloxonium tetrafluoroborate under the same reaction conditions, both isomers form predominantly 1-ethoxy-l-phenylethane with retained configuration, but the stereospecificity of the (Z)-product is higher (Moss and Landon, 1970; Moss and Powell, 1976). This is consistent with the C---O separation in the ion pair generated from either isomer ((Z): 7.55, (E): 7.56). N2 R+

1

f

-OEt

-OEt 7.55

7.56

The second method is based on the treatment of a diazenolate with thionyl chloride (Moss and Matsuo, 1976). As shown in (7-22), the carbocation and the chloride ion are separated by two neutral ("inert") molecules. With this method alkyl chlorides are produced with reduced retention of configuration. N

>> >>

N=N x

osoci

2

R+

c '

(

}

R—Cl

Micellar deamination is a method based on a special type of solvent effect. Originally, Moss (1971, p. 34) observed that deaminations of 1-methylheptylamine in water were characterized by rate constants up to 15 times higher, when conducted at higher concentration than the critical micelle concentration. As such deaminations are usually carried out at pH 3-5, the 1-methylheptylamine is present mainly as the ammonium ion. Not surprisingly, this ion has the properties of an amphiphile, i. e., an ion in which a lipophilic "tail" is joined to a hydrophilic head group. The latter may be cationic, as in the above case, or anionic, as in soaps and synthetic detergents, or nonionic, as in some textile auxiliaries. All these compounds form aggregates at higher concentration in water. The aggregates are roughly spherical with the polar groups on the surface and the hydrocarbon chains in the center. These micelles are in equilibrium with monomers. The driving force for micelle formation is the socalled hydrophobic bonding*. It is an entropy effect based on the hypothesis that * Hydrophobic interactions would be a more adequate expression. For reviews on micelles and hydrophobic interactions, see Fendler and Fendler (1975), Menger (1979), Turro et al. (1980), Lindman and Wennerstrom (1980), Burdett (1983), and Vitaglioano (1983).

7.3 Deamination Mechanisms of Open-Chain Amines: Substitution Products

269

water molecules in the immediate neighborhood of amphiphilic ions or molecules have a more ordered structure (clusters, so-called "iceberg" structure). The increase in deamination rate in the presence of micelles is also observed if amphiphilic compounds, not involved in the deamination proper, are added (e.g., trimethyl-1-methylheptylammonium salts; Moss, 1971). More interesting than the overall rate increase of deaminations in the presence of micelles is the influence of the latter on the configuration of the deamination products, as described in the pioneering investigation of Moss et al. (1973 a). In dilute aqueous perchloric acid 1-methylheptylamine is deaminated by nitrous acid to give predominantly octan-2-ol with inversion of configuration (and elimination products), if the concentration of the amine is below the cmc. Above this concentration, the amount of the configurationally inverted product decreases more and more. At a total amine concentration that is five times higher than the cmc, racemic octan-2-ol is formed, and, at still higher amine concentration, the result is increasing net retention. This effect is only observed, however, when perchloric, tetrafluoroboric, alkane-, or arenesulfonic acid is used, but not with hydrochloric, hydrobromic, or acetic acid. The anions of these two groups of acids are characterized by low and high degrees of hydrate formation, respectively. Therefore, the immediate aqueous layer adjacent to the ammonio groups of the 1-methylheptylammonium ion at the surface of the micelle (Stern layer) contains counterions of the first group in a denser form than that in the Stern layer with chloride, bromide, or acetate ions, which contains more water molecules*. The micellar stereochemical control was, therefore, explained by Moss et al. (1973 a) by the proposal of front-side return for retention and by the change in polarity at the reaction site (see also Kirmse et al., 1977, Sect. 7.4). The less polar solvent favors front-side attack and leads, therefore, to retention. Brosch and Kirmse (1993) applied their stereochemical technique for the deamination of optically active [l-2H]butylamine (Brosch and Kirmse, 1991) to that of (R)[l-2H]octylamine. They found similar micellar effects with respect to the ratio of octan-1-ol, octan-2-ol, octan-3-ol, and octan-4-ol, and other products (a total of ten compounds) as Moss et al. (1973 a) observed for 1-methylheptylamine. Yet, the configuration of the main product [1-2H]octan-1-ol was different: below the cmc, ca. 95% inversion was found, but above the cmc the enantiomeric purity of [1-2H]octan-1-ol decreased to 80.0%, whereas l-nitro[l-2H]octane was formed with 89,6% retention of configuration and yields between 4.6 and 10.3% (0.3-0.6% below cmc). These results indicate different mechanisms for primary amine (Brosch and Kirmse) and 1-methylheptylamine deamination (Moss et al., 1973a). The authors explain the partial racemization in octan-1-ol under cmc conditions, as well as the formation of 1-nitrooctane, by involvement of a radical pair 7.58 as the characteristic intermediate formed from the diazonitrite 7.57 as shown in * In a short communication without experimental details and little interpretation of data, Singer et al. (1982) describe deamination of octylamine in water in presence of bromide and chloride ions, which shows that, in these cases, the product ratio RX/ROH (X = Cl or Br) increases significantly above the cmc. More dramatic changes in selectivity RBr/ROH were found by Moss et al. (1982) for a micellar aromatic dediazoniation (see Zollinger, 1994, Sect. 8.3).

270

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

mechanism (7-23)*. More experimental evidence for this mechanism could be welcome, particularly in comparison to the other homolytic deamination reaction found and well documented by Kirmse's group shortly before this investigation on micellar deamination (Bunse et al., 1992). R—N2+

NO2"

^_ >

R—O—NO

CN "CN 7.60

^^ ^^*-

7.61

OH CN 7.62

(7-24)

7.64

* Mechanism (7-23) is a simplified version of Brosch and Kirmse's proposal.

7.4 Eliminations and Rearrangements in Deamination of Open-Chain Amines

271

As mentioned at the beginning of this section, Kirmse and coworkers (Bunse et al., 1992) found the first clear case of a homolytic aliphatic dediazoniation * As shown in Scheme 7-24, the aqueous diazotization of 2-amino-2-methylpropanenitrile (7.59) with two equivalents of NaNO2 (or N2O4) yields products that are likely to be formed from the carbocation 7.60, namely 2-hydroxy-2-methylpropanenitrile (7.62) and 2-methylprop-2-enenitrile (7.61), but also 2-methyl-2-nitropropanenitrile (7.64), and the 7V,7V-disubstituted 2-amino-2-methylpropanenitrile (7.66). The two last-mentioned products are probably formed via the radical 7.63. Direct evidence for this radical was found by experiments conducted in the presence of the radical scavenger 2,2,6,6-tetramethylpiperidin-l-oxyl (TEMPO) to give 7.65 in good yield. In other experiments, dimerization and oxidation products of the radical 7.63 were identified. More recently, Kirmse and his coworkers found two other deamination reactions where product studies indicated the intermediate formation of radicals, namely the nitrous acid decompositions of 2-aminobutylnitrile (Bunse and Kirmse, 1993) and of the epimeric 2-aminonorbornyl-2-carbonitrile (Kirmse et al., 1993b). Like 2-amino2-methylpropylnitrile (7.59), these compounds are characterized by a CN group at the same C-atom as the NH2 group.

7.4 Eliminations and Rearrangements in Deamination of Open-Chain Amines We start this section with a short discussion of conformational control, because conformations of alkylamines and alkanediazonium ions are important factors for the deamination mechanisms. The distribution and configuration of products is often a function of the relative population of conformers. If two conformers yield two different products basically two cases have to be distinguished: 1) The activation energies of the forward and backward conformational equilibration are small relative to the activation energies of the reactions leading from each conformer to the respective product; the ratio of the two products is independent of the relative population of the two conformers. 2) The activation barrier in the conformation equilibrium is higher than that of the two product-determining steps; the product ratio is then a function of the relative population of conformers (see the discussion given by Kirmse, 1979; p. 183). Conformational effects were studied by Southam and Whiting (1982) in deamination of 1-propylpentylamine by diazotization, by decomposition of 7V-Nitroso-7V(l-propylpentyl)butyramide and of l-phenyl-3-(l-propylpentyl)triazene, as well as by protonation of 4-diazooctane (all in acetic acid). With all methods except the last, the (Z)/(E)-ratio of oct-3- and -4-enes was near 1:3. In the protonation of 4-diazooctane, however, roughly equal amounts of (Z)- and (£)-isomers were found. * Ambiguous cases were reported earlier by Curtin et al. (1962) and by Scherer and Lunt (1966).

272

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

This is consistent with an intimate diazonium ion-acetate ion pair, which loses N2 before it can stereomutate. We have already made brief reference to the population of conformers in octane-1-diazonium ion (7.31) in Section 7.3 when discussing the conclusions of Monera et al. (1989) on the deamination of octylamine (7-16). Here, we discuss first results of these authors and of Southam and Whiting (1982) on the elimination and 1,2-hydrogen shift. Scheme 7-25 shows that conformers 7.31 B and 7.31 C, with one /?-H-atom aligned tf/tf/periplanar to the departing diazonio group, should be more predisposed to elimination and rearrangement than conformer 7.31 A. The ratio of substitution to elimination is practically independent of pH (2-10). This excludes participation of hydroxide ions in the elimination process. A common hydrogenbridged intermediate (7.67), as proposed by Monera et al., is unlikely, but it may be a transition state in Scheme 7-25. Another case of a deamination in an alkaline medium with no observable (base-catalyzed) formation of olefin was reported by McGarvey and Kimura (1986).

H+ H

(7-25)

Rearranged products

Hydride shifts of the type indicated by Monera's intermediate 7.67 are the cause of the addition of nucleophiles at C-atoms other than that originally bearing the amino group and also for the formation of CC double bonds at more remote positions. Instructive examples of 1,2-, 1,3- and 1,4-hydride shifts (or multiple 1,2-shifts) were described by Southam and Whiting (1982) for the deamination of octylamine and 1-propylpentylamine in acetic acid. Apart from the product of direct substitution in 1-octanediazonium ion, octylacetate (46.0-47.7%), 1-methylheptyl-, 1-ethylhexyl-, and 1-propylpentyl acetates were found in decreasing yields (16.9-18.5%, 2.4-2.8%, and 0.15-0.19%, respectively). An analogous series of elimination products was also reported, namely 18.2-20.6% of oct-1-ene, 1.7-2.0%

7.4 Eliminations and Rearrangements in Deamination of Open-Chain Amines

273

of (Z)-oct-2-ene, and 0.23-0.52% of (Z)-oct-3-ene, and 7.7-8.1%, 0.85-0.95%, and 0.04-0.10% of (£>oct-2-, -3-, and -4-enes, respectively. We include a classical problem in deamination mechanisms in this section, namely the dediazoniation of 3- and 1-substituted allyldiazonium ions (7.68 and 7.69, respectively), although these reactions are not rearrangements in the usual sense. If these dediazoniations proceed via an allyl cation (7.70), then one expects that they should give identical mixtures of substitution products 7.71 and 7.72. At an early date, Young's group (Semenov et al., 1958) found, however, that the composition of the product mixture depends on the structure of the diazonium ion. The original explanation was based on the hypothesis of 'hot' carbocations formed from diazonium ions in contrast to the cations formed from allyl derivatives with other leaving groups. This hypothesis was subsequently abandoned on the basis of detailed investigations with labeled compounds by Kirmse's group (see below).

(7-26)

771

Nu 7.72

Allyl cations are also formed by dediazoniation of cyclopropanediazonium ions (7.73). Dediazoniation of this ion without synchronous ring opening is rather unlikely*. Reaction products of the three groups of diazonium ions 7.68, 7.69, and 7.73, each substituted with R = C6H5, CH3, C(CH3)3, or D, were determined in the presence of nucleophiles of varying concentration (Kirmse and Schtitte, 1972). The results demonstrate that the product ratios of the cyclopropanediazonium ion are the same as those of the secondary prop-2-enediazonium ion (substituent at C(l), 7.69), and that the ratios are independent of the nucleophile concentration. The product ratios 7.71/7.72 obtained with the primary prop-2-enediazonium ion (7.68), however, are higher and increase with [Nu~]. This strongly indicates that a significant part of this reaction is based on bimolecular substitution (frs in Scheme 7-14),

* It was observed, however, to a small extent (3-5%) with 1-alkylcyclopropanediazonium ions (Kirmse et al., 1986; Kirmse and Rode, 1987a and 1987b).

274

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

whereas such a mechanism is not detectable in the dediazoniation of the 1-substituted prop-2-enediazonium ion 7.69. Kirmse et al. (1975, 1977) investigated the product ratio of aqueous deaminations for which (3-methylalkan-4-yl)amines were used under various conditions in acidic solution, as well as with disodium pentacyanonitrosylferrate (7.7). The product distribution of alcohols formed from (2S)-l-ethyl-2-methylbutylamine (7.74) are given in Scheme 7-27 and Table 7-3.

7.75

7.76

(7-27)

h NaNO2 r

HX

40-50% alkenes + nitrite esters

A rather complex mixture of seven alcohols can be detected (besides alkenes and nitrites). The product ratio of the alcohols (normalized to 100 % in Table 7-3) is dependent on the initial concentration of the amine 7.74, on the nitrosating reagent and on the mineral acid used. The product ratio in HC1O4, to a lesser extent also in HC1, is dependent on the concentration of the amine, and is obviously also influenced by the cmc. The influence of micelles can be seen in the yields for 7.75, i. e., the product of "straightforward" substitution, and also in the configuration of the compounds formed by a 1,2-hydride shift, 3-methylhexan-3-ol (7.76) and

7.4 Eliminations and Rearrangements in Deamination of Open-Chain Amines

275

Table 7-3. % Products in the alcoholic fraction of (2S)-l-ethyl-2-methyl butyl-1-amine (7.74) after Kirmseetal. (1977).

NaNO2, HC1O4, pH 3.5 [7.74] = 2.80 M 1.30 0.41 0.08

7.75

7.76

7.77

7.79

27.1 29.7 34.8 32.4

62.8 54.2 48.8 55.2

(cmc = 0.72 M) 4.1 1.9 6.4 0.7 5.6 0.2 2.8 0.1

NaNO2, HC1, pH 3.5 [7.74]- 3.30 M 1.40 0.27

51.4 47.9 38.3

33.9 40.3 43.5

(cmc = 1.4 M) 6,9 0.5 2.5 6.0 -

Na2[Fe(CN)5NO], K2CO3, H2O [7.74] = 0.116 M

24.0

65.0

3.8

0.5

7.78

3.3 7.3

7.80t

0.5 9.0a) 10.6a) 1.5

7.80e

0.3 0.7

7.3a) 9.3a) 12.3a)

6.7a)

a

) Sum 7.78 + 7.80t + 7.80e.

4-methylhexan-2-ol (7.77). The evaluation shows that the product 7.76 consists of a fraction formed in free solution with dominant inversion and a fraction formed in micelles with dominant retention. In HC1 the influence of the cmc is smaller. These results correspond to the experience of Moss et al. (1973) with 1-methylheptylamine (see Sect. 7.3). In the alkaline deamination, both the yield and the retention of configuration is almost twice as high as in acid (40.8% retention). Kirmse et al. (1977) explain this result tentatively by the assumption that nitrosation and dediazoniation take place within the ligand sphere of the complex metal ion. The fractions of 7.76 and 7.77 are so heavily influenced by these factors that bridged ions (alkeneprotonium ions) are unlikely to be the cause for product determination. Quite clearly, the reaction prefers an H-shift to the tertiary C-atom (7.76). 3-Methylhexan-2-ol (7.80) is a product of a 1,3-H shift. If such a shift takes place directly, the chiral center is not involved and both diastereomers (7.801 and 7.80 e) should have the same enantiomeric purity of the starting amine 7.74 (94%). This was indeed found to be so for 7.80t (95 ± 5%), but not for 7.80e (55 ± 5%). This result is consistent, however, with an H-shift in a protonated cyclopropane (7.81 -> 7.82 + 7.83). This concept was verified by the deamination products of [2-2H]-7.74 (Scheme 7-28). The formation of 3-ethylpentan-2-ol (7.78) is consistent with a mechanism that includes formation of the protonated cyclopropane 7.81 and additional H-shifts therein. The tertiary alcohol 3-ethylpentan-3-ol (7.79) is likely to be formed by a further 1,2-H shift from 7.78. Additional work of Kirmse's group with (1^25)-l,2-dimethylpentylamine and, later with (27?,3S)-3-methyl-2-pentylamine is also consistent with the mechanisms discussed above (Kirmse and Prolingheuer, 1980; Kirmse et al., 1980a, 1980b; Banert et al., 1986).

276

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

(7-28)

7.80t

The classical organic substituent that undergoes a shift in nucleophilic aromatic substitutions via a bridged cationic intermediate is the phenyl group. The first stereochemical evidence for such a shift was obtained by Cram (1949) in the acetolysis of l-methyl-2-phenylpropyl-4-toluenesulfonate. In this and related systems with an aromatic ring in the a-position to the reacting C-atom, the aryl group, behaving as a neighboring group, forms a bridged ion, i. e., the phenonium ion (7.84) in a concerted step with the release of the leaving group (7-29). The result is that either a substitution product 7.85, with retention of configuration, or a product with rearranged aryl group (7.86) is formed, whereas in the classical ANDN attack (SN2), the product 7.87 is configurationally inverted (7-29).

(7-29)

7.87

An instructive comparison of the ease with which groups undergo rearrangement in deamination was carried out by Kirmse et al. (1980 c) with enantiomerically pure substituted 2-phenylalkylamines (7.88) in aqueous HC1O4 (pH 3.5). As shown in Table 7-4, evaluation of the products demonstrates that "direct" substitution is responsible for only a small fraction and that phenyl shifts are by far the most important rearrangement. This fact was already known from many other investigations.

7.4 Eliminations and Rearrangements in Deamination of Open-Chain Amines

277

New evidence, however, is provided for the increase in alkyl shifts with increasing volume of the migrating alkyl residues at the cost of phenyl migration. Products obtained by a phenyl shift from the 2- to the 1-position, i. e., by migration from a secondary to a primary C-atom, have complete inversion of configuration at the 2-position *. This result is consistent with the phenonium ion as intermediate. The reaction products of the third entry in Table 7-4 (OR)-3-methyl-2-phenylbutylamine) were compared with the hydrolysis products of (/?)-3-methyl-2-phenylbutyl-4-toluenesulfonate. The major difference between these two reactions is the observation — supported by 2H-labeling — that isopropyl migration can successfully compete with phenyl migration only in the deamination. This lower selectivity of alkanediazonium ions in rearrangements is well known and is due to less neighboring group participation (see Cram and McCarty, 1957). Table 7-4. Reaction pathways in deamination of 2-arylalkylamines (7.88) in % (after Kirmse et al. 1980 c).

H — C — CH2NH2

R

CH3 C2H5 CH(CH3)2 C(CH3)3 a

Configuration of amine (S) (S)

(R) (S)

R "direct" hydrolysis 5.3 7.1 3.9 5.2

7.88 Rearrangements a

~H

~ Alkyl

~C6H5 )

13.2 8.9 18.4 10.7

5.7 6.7 13.4 32.9

72.3 76.5 62.9 44.8

Not identified 3.5 0.8 1.4 6.4

) Including products of consecutive steps after the phenyl shift.

In spite of limited space**, we have discussed deaminations in these thorough investigations of Kirmse and coworkers in some detail because they demonstrate nicely some of the causes for the complex variety of products formed in deamination in addition to those discussed in Section 7.3.

* For alkyl migrations the degree of inversion decreases from 70% (methyl) to 55% (tert-butyl) (Kirmse et al., 1980b). ** Reactions that proceed via bridged transition states or intermediates belong to those processes with anchimeric assistance. For more detailed discussions, see the comprehensive monograph of Capon and McManus (1976) and the review of Kirmse (1979, p. 196).

278

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

1.5 Deamination of Alicyclic Amines As discussed in Section 7.4, conformational control in deamination of open-chain amines is difficult to evaluate because the activation energies of conformational changes are often smaller than those of the steps in deamination reactions. Alicyclic amines are more suitable for such mechanistic investigations. In addition, the conformers of such amines can be locked if they contain bulky substituents (tert-butyl) or if the amines are based on bi- and polycyclic hydrocarbons (decalinamines, cholestaneamines, norbornylamines, etc.). We shall therefore concentrate first on the deamination of the epimeric 4-(tert-butyl)cyclohexylamines. Then, we will discuss the structural problems of cyclic carbocations formed in deamination of norbornylamine, cyclopropylmethylamine, and cyclobutylamine, i. e., compounds that are at the center of interest in the debate on classical versus nonclassical carbocations. The most extensive investigation on the deamination of trans- and cis-4-(tertbutyl)cyclohexylamine (7.89 and 7.90, respectively) by the three procedures mentioned was conducted by Whiting's group (Maskill et al., 1965; Maskill and Whiting, 1976) in acetic acid (in part in butyric acid). The amount of work involved in the deamination of ten different starting materials becomes evident from the fact that a total of 17 and 12 products was detected and analyzed for the experiments in the trans- and the ds-series, respectively. The corresponding tables contain 116 analyses! The products are cycloalkenes (from elimination), acetates and butyrates from external substitution, and products of internal substitution (ArNH, AcO, OH, depending on the procedure used). Two isolated products, obtained in 0.3-0.5 % and 2.5% yield, were identified later by Whiting's group (Cooper et al., 1982), as cis- and ^ra/w-S-butylcyclopentylmethyl esters, i. e., products of ring contraction. Maskill and Whiting's investigation is of general interest: it allows comparison of yields in the ten reactions. Dediazoniation via triazenes (7.91 and 7.92) gives very good yields: 93-99% (cis) and 77-85% (trans); via nitroso amides (7.93 and 7.94) 55% (cis) and 75-84% (trans) are reported. Direct deamination yields are low, as expected (18% for cis, 14% for trans). Nevertheless, it is interesting to note that the yields in c/s-deamination can be doubled (37%) when the reaction is conducted under nitrogen*. Comparison of product distributions from cis- and tows-precursors demonstrates clearly that there are practically no feasible common intermediates that allow a crossover between the two series. This is best shown from the total extent of hydride shift, which is very low for all six experiments with trans-amine and its derivatives (1.3 to > 2.2%), but high in the c/s-series (>26% to >34%; >14% for direct deamination). 4-(teAt-Butyl)cyclohex-l-ene is an elimination product formed in relatively small amount (7.6-17%) from trans-compounds, but it is by far the dominant product in the c/s-series (70-78%). In external substitution by acetate this result is reversed. Internal substitution accounts for 15.1-44% of products with the trans* Occasionally, such improvements in yield under an inert atmosphere were also reported for other deaminations, but they have never been evaluated mechanistically, to the best of our knowledge.

Diazo Chemistry II: Aliphatic, Inorganic and Organometattic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

7.5 Deamination of Alicyclic Amines

7.89

Z = NH2

7.91

Z = NH —N 2 —Ar a )

7.93

279

7.90 b

Z = N(NO)COR )

7.92 7.94

a

) Ar = C6H5> and C6H4-4-NO2

b

) R = CH3, in part also n-C3H7

reagents, but only for 3.1-11 % with c/s-compounds. The dominant substitution products of tarns-reagents are neither rearranged nor inverted. These major products are formed by external substitution in reactions of triazenes (52-56%), of the nitrosobutyramide (38%), and in direct deamination (56%), but by internal substitution in reactions of nitroso-acetamide (34-36%). Without further discussing other product distributions, we emphasize the high stereospecificity of these deaminations, which excludes interpretations involving free or symmetrically solvated carbocations as the principal reaction pathway. In Maskill and Whiting's opinion (1976), they are consistent with mechanisms involving fragmentation of diazene intermediates (R-N 2 -X) to give unrearranged and rearranged ion pairs initially separated by N2, i.e., a mechanism previously suggested for other deaminations by Moss (1974, see Sect. 7.3)*. The approximately equal yields of products from internal (X) and external (Y) nucleophiles can be explained by the formation of hydrogen-bonded species [X--«H•••¥]", e.g., [CH3CO2"-H---O2CC3H7]~. Such paired hydrogen-bonded anions may also explain, in part, the large solvent effect of the 4-c/s//raAZS'-substitution product ratio for direct deamination of tatfw-4-(tert-butyl)cyclohexylamine. In water this deamination proceeds with predominant retention of configuration because no analogous ion pairs can be formed (see Kirmse's interpretation in Kirmse and Siegfried, 1983, and Banert et al., 1986). In Schemes (7-30) and (7-31), the formation of ion pairs with such twinned anions is shown for the diazo compounds derived from the trans- and the ds-amine (7.89 and 7.90), respectively**. The products of reactions (7-30) and (7-31) are comparable to the triple ion pairs of Moss in (7-7) and (7-20).

(7-30)

* We assume that a mechanism via diazonium ions is not ruled out. See also Section 7.3 for the striking difference in the stereochemistry of deaminations starting with (Z)- and (£>diazenolates. ** X=HO-, ArNH-, RCOQ-; HY=R'COOH (solvent). For another position of [X-H-Y]after a 2,1-hydride shift in such an ion pair, see Maskill and Whiting (1976, Scheme 2).

280

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

- HY

(7-31)

With these mechanistic interpretations in mind, it is no longer surprising that the deamination products of 4-(teAt-butyl)cyclohexylamine derivatives are so different from those formed in solvolysis of the diastereomers of 4-(tert-butyl)cyclohexyl 4-toluenesulfonyl arylates, investigated by Winstein and Holness (1956), by Whiting's group (Campbell et al., 1968) and others, and in solvolysis of the corresponding trifluoromethanesulfonates (Traynham and Elakovich, 1973). Both diastereomers give predominantly elimination products (70-80% unrearranged cyclohexene), configurationally inverted products of substitution (11-21%), and similar amounts of products resulting from 1,2-hydride shifts. All these products are consistent with dominant crossover from the diastereomeric precursors through a common carbocation. For another classical problem of nucleophilic aliphatic substitution and rearrangement, namely pinacolic deaminations and rearrangements, the use of cyclohexane derivatives with a tert-butyl group instead of open-chain alkane derivatives was very helpful. The stereochemistry of these reactions was studied first by Bernstein and Whitmore (1939). Specific labeling with 14C, used first by Collins and his coworkers (Benjamin et al., 1957), helped significantly to elucidate the complex pathway of pinacolic deamination. Even summarizing the results would take far too much space here. The next focus of this section is deamination of exo- and efldo-2-norbornylamine because these reactions belong to the group of aliphatic nucleophilic substitutions in bicyclo[2.2.1]heptyl systems, for which Winstein and Trifan (1949, 1952) postulated a new type of carbocation intermediate, which was later called a nonclassical ion (see Bartlett, 1965, page V; Roberts, 1990, p. 67). We will, therefore, first briefly discuss nonclassical carbocations in general and then deamination in bicyclo[2.2.1]heptyl systems. Winstein and Trifan found that the acetolysis of ejto-2-norbornyl 4-bromobenzenesulfonate (7.95) resulted in a racemic mixture of the two exo-acetates (7.98 and 7.99). The endo-isomer (7.96) also gave the ejco-acetates, which were at least 93% racemic, but the endo-compound reacted about 350 times slower than the exo-isomer (Scheme 7-32). These results were rationalized by Winstein and Trifan for the exocompound by assistance of the C(l) — C(6) bonding electrons in the departure of the leaving group by which the nonclassical carbocation intermediate (7.97) is formed. The latter will be attacked at the C(l)- and C(2)-atoms by the nucleophile and, therefore, a racemic mixture of the exo-acetates is formed. Solvolysis of the endoisomer (7.96) cannot profit from participation of the C(l) - C(6) bond because those electrons are not in a sterically favorable position for backside attack. Therefore, the

7.5 Deamination ofAlley die Amines

7.96 - OBs

281

°BS

_ QBs

(7-32)

7.98

7.99

endo-acetolysis is much slower than the exro-acetolysis, although the rate roughly corresponds to that of acetolyses of alkyl bromobenzenesulfonates that follow the DN + AN mechanism. Since the 1950's, an enormous amount of work has been carried out on other nucleophilic substitutions of norbornane derivatives and related compounds. This was particularly due to the alternative mechanistic explanation proposed by H. C. Brown in 1962 (see also Brown, 1966, 1976, 1977). He postulated that instead of the nonclassical intermediate 7.97, the expected classical carbocation 7.100 is formed in a rapid equilibrium with the ion 7.101. In his opinion, 7.97 is not an intermediate, but corresponds to the transition state in the equilibrium 7.100^7.101 (Scheme 7-33). Arguments for and against Winstein's and Brown's proposals by other researchers can be found first of all in Bartlett's anthology (1965) and in the literature until the present day (see some 30 references in the period 1977-1988 in March's book, 1992, p. 321)*.

7.95

+-

L 7.100

7.101

* J. D. Roberts described this debate in a particularly revealing way in his autobiography (Roberts, 1990, p. 66-68, 82-89, 250-259).

282

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

Particularly in the first half of the more than forty years since Winstein and Trifan's proposal, the contributions concentrated mainly on kinetics and product ratios of 2-norbornane derivatives * Olah's development of superacid media ("magic acid", see review of Olah et al., 1985d) allowed preparation of stable solutions of aliphatic carbocations. As a result, direct spectroscopic investigation with UV, IR, NMR, etc., became feasible for carbocations in general and for the 2-norbornyl cation in particular (NMR in liquid phase: Olah et al., 1982; NMR in solid phase: Yannoni et al., 1982; IR: Koch et al., 1989, 1990). It would be very interesting for the problem of the existence of the nonclassical 2-norbornyl cation to determine the crystal structure of one of its salts. Due to the generally low stability of such salts, it was not possible to analyze a salt of the unsubstituted 2-norbornyl cation. Laube (1987) was, however, successful in obtaining a crystal structure of the l,2,4,7-tfft#-tetramethyl-2-norbornyl cation (as salt with Sb2Fn, 7.102).

Atomic distances: C(1)-C(2) 144 pm C(1)-C(6) 174 pm C(2)-C(6) 209 pm Other CC bond lengths in the five-membered ring: 150-155 pm (details see Laube, 1987)

The atomic distances between C(l), C(2), and C(6) found by Laube are consistent with a bridged carbocation. Particularly interesting are the correlations between the experimental IR and NMR spectra of the 2-norbornyl cation and theoretical predictions of such spectral data. The IR spectrum published by Koch et al. (1990) was recorded using Vancik and Sunko's technique (1989) in which 2-chloronorbornane and SbF5 are deposited simultaneously from the gas phase on a Csl window at 77 K. During a slow temperature increase to 150 K, formation of the carbocation could be observed by the change in the IR spectrum. Koch et al. (1990) compared the frequencies and intensities of 21 absorption bands observed in the range 878 — 3110 cm"1 with results that were calculated on the basis of a structure of the nonclassical 2-norbornyl cation obtained by Koch et al. (1989) using the 6-31G* basis set and dynamic electron correlation on the MP2 level. The calculated IR bands correlated very well with the experimental frequencies and intensities. The calculated structure of this cation was, * In 1987 more than one hundred substituted 2-norbornyl derivatives were known (Laube, 1987).

7.5 Deamination of Alicyclic Amines

283

therefore, clearly verified by the IR spectrum. The calculations of the energy hypersurface showed only one minimum (that of the nonclassical ion) and not two, as expected for equilibrium (7-33). A similar comparison between experiment and theory was accomplished for the experimental 13C NMR spectra of the 2-norbornyl cation (Yannoni et al., 1982; Myhre et al., 1990a), using CPMAS (cross polarization magic angle spinning for solid-state NMR) and applying the IGLO procedure (individual gauge for localized molecular orbitals) developed by Kutzelnigg and Schindler (Kutzelnigg, 1980; Schindler and Kutzelnigg, 1982; Schindler, 1987 a). The IGLO method gives particularly successful consistency between theory and experimental NMR spectra (*H and 13C) for bridged carbocations (Bremer et al., 1989). All theoretical and experimental results are consistent with a symmetrically bridged structure for the 2-norbornyl cation*. The interatomic distances of the C(1)-C(6) and C(2)-C(6) atoms were calculated to be 182.9 pm and that of the C(1)-C(2) atoms 139.4 pm. Comparison of the 13C NMR spectrum of the 2-norbornyl cation (Myhre et al., 1990) with that of its 1,2-dimethyl derivative (Myhre et al., 1985) shows, however, a very important difference. In the spectrum of the 2-norbornyl cation, the position of the signal for the C(l) and C(2) atoms is constant in the temperature range 6-120 K, whereas that of the dimethyl derivative is split above 80 K. This observation indicates that, in the latter, an equilibrium exists between two nonsymmetrical, partially bridged, structures (7-34). This equilibrium was already detected by Goering and Humski (1968, 1975; see also Goering and Clevenger, 1972)**.

(7-34)

In the context of the historical development of our knowledge of the structure of the 2-norbornyl cation since Winstein and Trifan's postulate in 1949, this comparison with the 1,2-dimethyl derivative is very important for aspects provided by the theory of scientific discoveries. As discussed in our book on aromatic diazo compounds (Zollinger, 1994, Chap. 9), verifications are never definitive, in science "proofs" are not possible (the term proof should only be used in mathematics); falsifications, however, can be definitive. It was shown that molecular orbital calculations and their application to experimental data on the IR and NMR spectra for the 2-norbornyl cation are consistent with a symmetrical, nonclassical cationic intermediate, but not with a rapid equilibrium between two classical intermediates. The

* The tf«/7-l,2,4,7-tetramethylnorbornyl cation has, however, an unsymmetrically bridged structure as shown in formula 7.102. ** Kinetic investigations and product analyses of substituted norbornyl arenesulfonates were made by Grob's group (Bielmann et al., 1988; Flury et al., 1988) and evaluated in a slightly different way. Their interpretation, however, is not consistent with theory (see Lenoit et al., 1988).

284

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

latter hypothesis is, therefore, falsified — it is, however, falsified only for this cation ! The experiments with the l,2-dimethyl-2-norbornyl cation demonstrate that, in that closely related compound, an equilibrium does exist. In addition, the data indicate partially bridged structures for the two equilibrium partners. Brown's opposition to all nonclassical ions in cyclo[2.2.1]alkane systems now has to be abandoned for the most frequently investigated cation, but, based on the evidence for an equilibrium of two isomeric cations in (7-34), his hypothesis is not generally falsified. There are three relatively short, recent reviews in which the structural problems of the 2-norbornyl and other carbocations are discussed for the general reader. Both were written shortly after the decisive theoretical and experimental investigations were carried out, namely by Schleyer's group (Buzek et al., 1992), by Kirmse (1992), and by Walling (1993). Buzek et al. do not, however, clearly follow the principles briefly discussed in the preceding paragraph of this section. The 2-norbornyl cation is part of the group of hypervalent carbon compounds, which are discussed in the books of Olah et al. (1987) and Minkin et al. (1987). Hanack (1990) edited a volume of Houben-Weyl on carbocations. Berndt (1993) described interesting correlations between nonclassical carbocations of the type discussed above with related compounds among methylidene-boranes After this general discussion of the nucleophilic substitution of norbornane derivatives, we will concentrate on the deamination of exo- and e/ic/o-2-norbornylamine. The acetolysis of norbornanediazonium ions was first studied by Corey et al. (1963) and by Berson and Remanick (1964). Their results could not be interpreted easily either by Winstein's or by Brown's hypothesis, as seen, for example, in Bartlett's annotated reprint collection (1965), in which he emphasized the need for fully resolved reagents and for better separation methods. Two decades later, the methodology was significantly better for both these aspects. Therefore, Kirmse and Siegfried (1983) investigated the deamination of both enantiomeric amines again, not only in acetic acid, but also in water and in two carboxylic acids with large alkyl groups (3,3-dimethylbutyric acid and 2-ethylhexanoic acid), which are less polar than acetic acid. In water (HC1O4, pH 3.5), exo-2-norbornylamine (7.103) yielded racemic exonorbornan-2-ol (7.109, R=H) and less than 0.1% endo-alcohol (7.110, R=H). The e/z6fo-2-norbornylamine (7.104), however, gave 10.2% endo-alcohol with complete retention of configuration and 89.8 % of almost racemic exo-alcohol. Experiments with the two enantiomeric 2-norbornylamines labeled with deuterium in the 2-position demonstrated that hydride shifts are minimal. The racemizations observed are, therefore, almost entirely due to Wagner -Meerwein rearrangements (Scheme 7-35). The results of deaminations in acetic acid were in agreement with those of Berson et al. (1964), i.e., partial retention in the exo-acetate (10.5% and 20.5%; 7.109, R = COCH3) obtained from the exo- and from the endo-amine, respectively, but practically full retention (98 ±2%) of the endo-acetate (7.110, R=COCH 3 ) obtained from 7.103 and 7.104. In the less polar carboxylic acids, the authors observed increasing yields of the endo-ester from the exo-amine, decreasing yields of endoester, and increasing enantiomeric purities of exo-alcohols and exro-esters.

7.5 Deamination of Alley die Amines

285

(7-35)

7.112

7.109

7.110

OR

R = H, COAlk

Most interesting in these products are the endo-alcohols and e«rfo-esters formed. Kirmse and Siegfried argue against their formation by trapping of a classical norbornyl cation (positive charge in 2-position), but for intermediacy of the 7-bridged norbornyl cation (7.108), which is also formed in the rearrangement of bicyclo[3.1.1]heptyl derivatives (7.111, Kirmse et al., 1983; Kirmse 1986) and in the protonation of tricyclo[3.2.0.02>7]heptane (7.112, Davis and Johnson, 1974; Kirmse and Streu, 1987). The optically active exo-products from the exo-amine may result either from a chiral norbornyl cation, but, more likely, as emphasized by Collins (1975), by asymmetry in the diazonium-carboxylate ion pairs, which give carbocation-carboxylate ion pairs (see Scheme 7-17 in Sect. 7.3). The authors emphasized, however, that these "product studies cannot distinguish a rapidly equilibrating and highly exo-selective classical norbornyl cation from the bridged species" 7.107 and 7.108 as intermediates (Scheme 7-35).

286

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

Manuilov and Barkhash (1985) interpret the product ratios in the deamination of 3,4,5,6-tetrafluorotricyclo[6.2.2.02'7]dodeca-2(7),3,5,9-tetraene-ll-e«^oand ll-exoamine (7.113 and 7.114) and -dodeca-2(7),3,5-triene-9-e/zrfo- and 9-exro-amine (7.115 and 7.116) in an analogous way as Kirmse and Siegfried (1983), i.e., with two competitive carbocations, bridged in the 3,4,5- and in 4,5,8-positions. The F-atoms in the aromatic ring make it possible to determine the degree of epimeric purity of the reagents and the products with high accuracy by means of high-resolution 19F NMR spectra. Product ratios were determined in acetic acid, methanol, and DMSO, and compared with product ratios of solvolysis of the corresponding arenesulfonates.

7.113

X = NH2) Y = H

7.115

X = NH2, Y = H

7.114

X = H, Y = NH2

7.116

X = H, Y = NH2

Kirmse et al. (1991) came more closely to a differentiation between classical and nonclassical carbocation intermediates in deamination by the photolytic formation and nucleophilic substitution of diazonium ions from the 4-toluenesulfonyl hydrazones of 6,6-dimethyl- and 5,5,6,6-tetraalkylnorbornan-2-one 7.117, 7.118 and 7.119 (Scheme 7-36). By running the reactions in D2O/NaOD, the diazonium ions were labeled with deuterium in the 2-position. For all three reagents, the alkylated exo-norbornanols (from 7.117: 7.120 and 7.121) showed a distribution of deuterium in positions 1 and 2 that was very close to 1:1 (49.5:50.5 to 47.6:52.4). If these deviations from an equal distribution were caused by two classical ion intermediates,

(7-36)

7.121 49.5%

7.5 Deamination ofAlley die Amines

287

the energy difference of the two classical intermediates should be less than 2 kJ mor1*. Deuterium label distributions in the deamination of exo- and ewcto-tricyclop.S.O.O2'7] octyl-6-amine (7.122 and 7.123, respectively) were determined in a joint investigation of Bentley and Kirmse (Bentley et al., 1988). The results indicate that the bicyclohexyl-type bridged ion structure 7.124 and the open structure 7.125 are approximately equivalent with respect to energy level, but that the norbornyl-type ion 7.126 is not involved in the deamination, a result that is in accord with MM2 force field calculations (Scheme 7-37). 7.122: X = NH2, Y = H 7.123: X = H, Y = NH2

x

Y

t7-37) \

\

/

I

*"

7.124 7.125

The three investigations summarized above (Manuilov and Barkhash, 1985; Kirmse et al., 1991; Bentley et al., 1988) are a selection from papers, published since the mid-1980's, which demonstrate that there are indeed deaminations with various types of cationic intermediates. In general, solvolysis of bicycloalkylarenesulfonates and halogenides give less complex product mixtures and higher yields of identified products than deaminations. The latter process occasionally may provide advantages, e. g., in the case of bicyclo[2.1.1]hexane derivatives (7.127), where reactions of the optically active 4-bromobenzenesulfonates were found to be obscured by internal return and inverting displacement (Kirmse et al., 1986b). At the end of this section, we discuss deamination of small-ring compounds with an amino group directly attached to the ring or via a methylene group, because nonclassical carbocations also appear in these reactions. Demjanov (1907) made the

7.127

* As discussed a long time ago (Zollinger, 1956; see summary: Zollinger, 1994, Sect. 12.8), such small energy differences may also be due to a "detour" around a single minimum.

288

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

puzzling observation that cyclopropylmethylamine (7.128) and cyclobutylamine (7.129) both gave about the same mixture of cyclopropylmethanol and cyclobutanol. Roberts and Mazur (1951 a) verified these results and showed that small amounts of but-3-enol are also formed (7-38). In addition, Roberts and Mazur (1951 b) demonstrated, by using cyclopropyl[14C]methylamine, that the 14C label was found in the 1- and 2-positions of cyclopropylmethanol (ratio 46 : 54) and in the 2- and 3-positions of cyclobutanol (72 : 28).

2—

NH2 or

7.128

<^\-NH2

HN 2

° >

[>-CH2OH + <^\—

7.129

ca. 48%

OH

ca. 47%

(7-38)

+ H2C = CH— CH2— CH2OH ca. 5%

Obviously, Roberts and Mazur draw the conclusion from the but-3-enol formed in (7-38) that but-3-enylamine would behave in the same way. Indeed, this is the case, but two new products were also found, but-3-en-2-ol (7.130) and but-2-en-l-ol (7.131). These products result from 1,2-hydride migrations. H2C=CH— CH— CH3

H3C — CH=CH— CH2OH

OH 7.130

7.131

Protolysis of cyclopropyldiazomethane in water gives essentially the same product ratio as shown in (7-38) (Moss et al., 1968 a). The decomposition of the deuteriumlabeled (cyclopropylmethyl)diazenolate in H218O afforded a slightly different ratio of cyclopropyl methanol- cyclobutanol (1.28 : 1) with little 16O, but extensive scambling of D (Moss and Shulman, 1968; Moss et al., 1968). All these fairly similar results are, however, in sharp contrast to solvolysis of cyclopropylmethyl chloride, which is much more reactive than cyclobutyl chloride or 4-chlorobut-2-ene (Roberts and Mazur, 1951 a). There was also positive evidence for internal return in the cyclopropylmethyl chloride solvolysis, although the solvent used (50% aqueous ethanol) is known to be unfavorable for internal return. Another reaction, closely related to the protolysis of cyclopropyldiazomethane mentioned above, is the reaction of that diazoalkane with ethereal benzoic acid. The product ratio cyclopropylmethanol: cyclobutanol = 5.8 indicated a strong decrease of skeletal rearrangement (Moss and Shulman, 1968). It is obvious from these (and other) investigations that the mechanism of these reactions is complex indeed. There are still open questions, but we will summarize how the experimental results are interpreted at present. The rationalization of the rates, and product and labeling ratios discussed above was based mainly on 13C NMR spectra in superacids and on high-level MO calculations.

7.5 Deamination of Alley die Amines

289

The methyl cation is increasingly stabilized if it is substituted by one, two or three cyclopropyl groups. This stabilization is a result of hyperconjugation between the bent orbitals of the 2,3- and 2,4-cr-bonds in the three-membered rings (7.132 A-7.132C) (see X-ray structures of Childs et al., 1990, and earlier literature cited there) and the C(l)-atoms. This is the reason for the greater reactivity of cyclopropylmethyl derivatives. The initially formed cyclopropylmethyl cation 7.132 can rearrange into other isotopomeric cyclopropylmethyl cations (7.133 and 7.134) and cyclobutyl cation 7.135 * (Scheme 7-39). Solvolysis of specifically labeled cyclopropylmethyl derivatives demonstrated that these rearrangements proceed stereospecifically (Majerski and Schleyer, 1971). 13C NMR spectra in superacid (amorphous SbF5) at low temperature (5-17 K) were interpreted as being consistent with a mixture of the "bisected" cyclopropylmethyl cations 7.132-7.134 and the cyclobutyl cations 7.135 (Myhre et al., 1990b; see also earlier work by Roberts' and Olah's groups: Staral et al., 1978; Prakash et al., 1985).

(7-39)

7.133

7.134

7.135

7.132

These NMR results are consistent with MO calculations performed independently by Koch et al. (1988) and by the joint groups of Saunders, Schindler, Schleyer and Wiberg (Schleyer et al., 1988) at the MP2/6-31G* and higher levels of theory (full fourth-order M011er-Plesset perturbation theory*). The C4H7+-system consists, in the light of these calculations, of a cyclobutyl cation (better described as a nonclassical pentacoordinated bicyclobutanonium ion, 7.135) and a bisected cyclopropyl cation (7.132) with an isomerization barrier of 2.5 kJ mol"1.

* There are several isotopomeric cyclobutyl cations 7.135, as already found by Roberts and Mazur (1951 b). ** Koch et al. (1988, Table I) give an instructive summary of previous theoretical results for various postulated structures of C4H7+cations (see also Koch, 1991).

290

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

1.6 A Challenge to Revisit Deamination Mechanisms In Sections 7.3-7.5, we discussed a selection of investigations on the deamination mechanisms of aliphatic amines by direct nitrosation in various solvents and by rearrangement processes of amine derivatives. These investigations are a very small fraction of all studies made in that area. It would take too many pages to summarize, and even more, to critically discuss the majority of all results. In 1983, Kirmse and Siegfried published a paper with the title "2-Norbornanediazonium Ions Revisited". These authors considered it essential to reinvestigate the deamination of the endo- and exo-norbornylamine, not least within the context of the well-known discussion on nonclassical carbocations. We adopt the word 'revisit' from this paper for this section and combine it with 'challenge', i. e., an expression indicating encouragement to reinvestigate deamination mechanisms in the future, because today (1995) we still have the impression that there are too many ambiguities in mechanistic interpretations of experimental results in deamination studies. Results obtained during the last ten years or so are certainly more reliable; Bartlett's statement in 1965 of a need for better resolved reagents and for improved separations of isomers for work on nonclassical carbocations was definitely appropriate. Care was taken successfully, as shown by the investigation of the deamination of [l-2H]butylamine by Brosch and Kirmse (1991) discussed in Section 7.3. We will use this reaction to demonstrate, however, that the conclusion that can be drawn from Brosch and Kirmse's result of a practically complete inversion of configuration in that deamination, namely bimolecular reaction following the ANDN mechanism, is likely to be unambiguous. Other mechanisms are also consistent only with partial inversion. One of them is included in Scheme 7-17, namely the formation of the ion pair 7.37, which leads to partial inversion. White et al. (1992b), when proposing Scheme 7-17, considered such a pathway as a 'minor path' for the 1-phenylethyl and for tertiary groups, the compound with retained configuration being expected as the major product. Another possibility is a reaction involving a carbocation with the front face shielded by the N2 molecule, as also considered by White (1993). Finally, Gautier's (1980) interpretation of the pyrolysis of chiral N[2H,3H]methyl-A/-nitroso-4-toluenesulfonamide (7-13, see Sect. 7.3) is also consistent with Brosch and Kirmse's result: Gautier considers that the methanediazonium ion rotates in order that the 4-toluenesulfonate ion can attack the carbocation from the rear. All these interpretations fit the experimental results - but which is the most credible? This question is, in our opinion, a typical case to be solved on the basis of Popper's book Logic of Scientific Discovery (1935, 1980): A hypothesis is postulated from observations. The hypothesis should then be tested by experiment, designed either to verify or to falsify the original hypothesis. A verification is never definitive and absolute, but a falsification is. If two or more hypotheses fit certain experimental results, a new experiment must be designed in such a way that it will verify one hypothesis, but falsify the other. By such a procedure, erroneous hypotheses can be

7.6 A Challenge to Revisit Deamination Mechanisms

291

abandoned. As discussed in our other book on diazo chemistry (Zollinger, 1994, Chapt. 9), the explanation why such a strictly logical procedure is not often followed is clear - the human mind prefers to verify and not to falsify! To decide difficult cases one often uses as a stopgap the principle of Ockham's razor, i. e., one choses that interpretation of a mechanism that is the simplest. If the basis for this choice is clearly declared as a stopgap, it is acceptable — in spite of the danger that, later, other scientists will quote that interpretation without reservation. The discussion for and against the existence of nonclassical carbocations lasted three decades (Sect. 7.5) and may be classified as an application of Popper's verification/falsification methodology although — to the best of our knowledge — no chemist involved in that process made explicit reference to Popper: experiments were designed in such a way as to differentiate between the existence or nonexistence of such ions. Classical physical-organic methods (kinetics, identification of product ratios, and product configuration) were, however, unable to answer that question, mainly because those carbocations were steady-state intermediates under conventional reaction conditions. That situation changed, however, when the techniques of superacid systems, low-temperature spectroscopy, including X-ray investigations, and more reliable molecular orbital calculations, became available (see Sect. 7.5). We are, therefore, convinced that the existence of nonclassical carbocations in nucleophilic substitutions of norbornanes and related compounds is now on such a fairly safe basis that a general rejection of their existence is no longer appropriate, particularly because relatively recent results demonstrate that similar reactions without nonclassical carbocations are also feasible. The general status of our knowledge on displacement and rearrangement reactions of such bicyclic hydrocarbon derivatives is, however, not yet so well worked out that reactivities and products can be predicted on the basis of generally applicable rules. As an example, we make reference to three deamination investigations of Kirmse's group, namely that of the two 2-norbornylamines, discussed already (Kirmse and Siegfried, 1983), that of l-methyl-2-e«cfo-norbornylamine (Banert et al., 1983), and that of eA2
292

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

of (jE')-l-methylpropyldiazenolate (Finneman et al., 1993), and the kinetics of four other simple (E)- and one (Z)-diazenolates (Ho and Fishbein, 1994; see also Finneman and Fishbein, 1994). The work on methylamine — clearly the simplest aliphatic amine — also demonstrates, however, that not only the amine, but also the deamination method must be simple. We discussed the stereochemistry of the deamination in the rearrangement of a derivative of chiral methylamine (7.30) in Section 7.3, but first, we have doubts whether Gautier's result (1980, inversion) of the pyrolysis of that 7Vmethyl-Af-nitroso-toluenesulfonamide in an aprotic solvent at 95 °C is comparable with the direct nitrosation of an amine in water, and second, the result of Gautier is contrary to that of the stereochemical investigation of a somewhat more complex amide deamination, namely that of N-(l-methylpropyl)-7V-nitroso-4-toluenesulfonamide (White et al., 1981; see Sect. 7.3)*. We consider general rules as useful for the development of scientific knowledge, but we admit that we are skeptical about apparent exceptions to such rules. We shall explain this skepticism with the help of a specific example. In 1870, Fittig and Jannasch found that in the reaction of durene (1,2,4,5-tetramethylbenzene) with one equivalent of nitric acid in sulfuric acid almost half of the durene yielded dinitrodurene and practically all the remaining durene could be recovered. Very little of the expected product, mononitrodurene, was found. Although a fairly large number of qualified and well-known chemists reinvestigated this problem during the following 99 years, including, for example, Willstatter and Kubli (1909), no explanation was found. This reaction became known as an exception to the well-documented general rule that the rate of introduction of a second nitro group into benzene or its derivatives is at least a thousand times slower than that of the first nitro group. In the case of durene, the primarily formed mononitrodurene was obviously nitrated for the second time at a rate at least fifty times faster than that of durene. The explanation of this phenomenon was found by Zollinger's group only in 1969 (Hanna et al., 1969; Hunziker et al., 1971). The first and the second substitution reactions are significantly faster than (micro)diffusion. When a droplet ("eddy") of the nitrating solution is added to the durene solution a peripheral, monomolecular zone of mononitrodurene is formed. This zone is still in immediate contact with the droplet of the nitrating solution. If the reaction of the mononitrodurene molecules with the nitrating reagent is faster than the diffusion of mononitrodurene molecules into the bulk durene solution, a large fraction of dinitrodurene will be formed, in spite of the fact that the intrinsic rate of the second substitution is about 103 times slower than that of the first (for a graphic representation see Zollinger, 1991, p. 125, Fig. 7-3). We referred to the durene nitration phenomenon, although an electrophilic aromatic substitution is not directly related to the reactions of this section. There may, however, be an indirect correlation because we have the impression that

* White postulated recently (1993) that this discrepancy between his and Gautier's results can be explained in terms of the lifetimes of the corresponding diazonium ions with respect to the carbocations.

7.6 A Challenge to Revisit Deamination Mechanisms

293

microdiffusion effects may have a more dominant role in deamination mechanisms than assumed hitherto. This is indicated by observations and interpretations by several authors, in particular by White et al. (1992b; see Sect. 7.3, Scheme 7-17) in his concept of inert molecule-separated ion pairs. It has to be assumed with a high degree of certainty that at least the diffusion of a (practically) inert molecule like N2 from a position between a cation and an anion has a rate typical for molecular diffusion. Such a process may easily influence product ratios to a large extent. We are, therefore, extremely skeptical whether it is appropriate to discuss products whose content in a product mixture is small *. As mentioned in previous sections, nitrosations of amines with recoveries of identified products greater than 80% are relatively rare (e.g., see Doyle et al., 1978, for the rather complex deamination of benzylamine with in situ generation of nitrosyl halides by titanium tetrahalides). Any mechanistic conclusions based on lower total yields are not sufficiently reliable. The relatively large amounts of unidentified products may be caused by homolytic processes. There are only two investigations of Kirmse's group on a deamination, in which clear evidence for homolysis was found (Bunse et al., 1992; Brosch et al., 1993; see Sect. 7.3). Yet, the observation of Maskill and Whiting (1976; see Sect. 7.5) that the change of the atmosphere from air to N2 had a significant influence on the deamination yield of cis-4-(tert-butyl)cyclohexylamine (7.90) also indicates that competitive homolyses may be responsible for low yields. A further cause for homolysis may be the relatively large excess of nitrosating compound (NaNO2, etc.) used in most direct nitrosations. The last-mentioned disadvantage of deaminations of amines with nitrosating compounds in aqueous and other protic solvents is, of course, not present if Af-nitroso amides and related compounds discussed earlier (7.10, and footnote on p. 246, concerning White's pioneering work) are used in aprotic solvents. Studies based on stereochemical comparisons of reacting amines that result in product racemization are usually interpreted as being due to the formation of a diazoalkane as intermediate. 2H-Labeling of the amine or the use of 2H-labeled solvents (D2O, CH3COOD, etc.) helps to test that hypothesis. Early examples were the investigations with nitroso amides in acetamide by Streitwieser and Schaeffer (1957 b) and in nonpolar solvents by White and Aufdermarsh (1957). The experimental results are, however, significantly different for deaminations of nitroso sulfamides (see Gautier, 1980, and White et al., 1980, as mentioned above) and demonstrate, therefore, that Af-nitroso amides of carboxylic and sulfonic acids cannot simply be compared with respect to their rearrangement and dediazoniation mechanisms. Investigations are not reliable if conclusions are drawn on the basis of statements about the extent of retention or inversion of configuration without such tests on potential formation of diazoalkanes as steady-state intermediates. * A similar statement was also made by Manuilov and Barkhash (1990), who mentioned two extreme cases of yields (0.039 and 0.114%) in a paper of Collins and Benjamin (1972). These examples are, in our opinion, not completely appropriate in this context, as Collins and Benjamin used these figures only for numbering exo/endo ratios of norbornyl derivatives where the other stereoisomer was formed in yields of 25.6% and 19%, respectively, i. e., where the large dominance of one isomer over the other had to be demonstrated.

294

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

I gave some examples of uncertainties in the last few paragraphs of this section because they are, to some extent, the reasons why we do not discuss deamination mechanisms in more detail in this book. Therefore, I did not try to provide generally applicable explanations for the fact that, in nucleophilic aliphatic substitutions, N2 as a leaving group often gives very different products from those obtained with halide ions or arenesulfonate ions as leaving groups. Experience during the last two decades demonstrates that early explanations of the type 'exceptions of a general rule' must be abandoned. The work of Kirmse's group demonstrated that various products obtained with diazonium ions are not due to different carbocations ('hot carbonium ions'), but to differences in the preceding compounds, i.e., the diazonium ion relative to the corresponding haloalkanes and alkyl sulfonate ester (see the review of Kirmse, 1976). In this context, a problem that was very important for the development of our knowledge on the stereochemistry of nucleophilic aliphatic substitutions with halide and arenesulfonate ions, is that of internal return, i. e. , the reverse reaction from an ion pair [R+ X~] (X = halide or sulfonate). Internal return has to be considered briefly for N2 as leaving group in deaminations. It has always been assumed that internal return does not occur in deaminations. Since the analogous reaction was identified positively, however, in dediazoniations of arenediazonium ions (Bergstrom et al., 1974; see Zollinger, 1994, Sect. 8.3), internal reaction of an aliphatic carbocation with N2 can no longer be excluded with certainty. It is, however, less likely, as it was shown that, in the breaking and forming of a single bond between an aromatic carbon atom and N2, n-n bond interactions are important (Zollinger, 1990a). Such an effect is not feasible for alkanediazonium ions. The applicability of the Hammond postulate and the Curtin-Hammett principle was discussed in the review of Manuilov and Barkhash (1990) on the mechanism of deamination. This principle allows evaluation of the effect of conformational changes on the reactivity of compounds A and A' forming B and B' in the kinetic system (7-40), in which the steps with rate constants k\ and k3 may be monomolecular or bimolecular (with a reagent R); A and A7 are conformers of the starting material. B

«

1

A(-fR)

<

> A'(+R) -

- B'

(7-40)

The basic concept was developed by Curtin in 1954 and shortly after also by Winstein and Holness (1955). Complete kinetic analyses were published considerably later by Katritzky's group (Imbach et al., 1966) and by Seeman et al. (1980)*. The extensive review of the applications and extensions of Curtin-Hammett/Winstein-Holness kinetics published by Seeman (1983) demonstrates, in our opinion, that the kinetic data available today are not sufficient for a quantitative evaluation of deamination by these concepts. * For Hammett's contribution and early criticisms by various authors, see Seeman's review (1983).

7.7 Synthetic Applications of Deamination Reactions

295

In conclusion, we propose a specific research program for deaminations in aqueous systems based on ideas mentioned in this section, namely to investigate (a) deamination kinetics and products of a series of simple aliphatic amines in water with sodium nitrite and perchloric acid at various acidities, (b) decompositions of diazenolates of the same amines in water and (c) decompositions of a standard type of 7V-nitroso amides, again of the same amines and all in the same aprotic solvent. The reaction conditions should be as similar as possible in the experiments of all three series. The series of amines should include methyl-, ethyl-, 1-methylethyl-, 1-methylpropyl-, and (tert-butyl)amine and [l-2H]ethylamine, but not amines with longer aliphatic chains, as the very informative work of Southam and Whiting (1982) demonstrated clearly that, in deaminations of such amines, many mechanistically complex products are formed. In addition, micellar effects increase the complexity of reactions with such amines (see Sect. 7.3). It is obvious from the series of amines that we have proposed that this program is based on the work of Brosch and Kirmse (1991), Hovinen and Fishbein (1992), Hovinen et al. (1992), Finneman et al. (1993), and Ho and Fishbein (1994). Work with chiral 1-methylpropyl- and [l-2H]ethylamine will provide information on the stereochemistry of these reactions. Investigations with 7V-nitroso amides and related 7V-nitroso compounds have the advantage that many difficulties with combined nitrosation and dediazoniation processes (as discussed above) can be avoided. Their results cannot, however, always be applied for an understanding and improvement of the most classical deamination method, i. e., the hydroxy-de-amination of an amine in an aqueous nitrosation.

1.1 Synthetic Applications of Deamination Reactions It has already been mentioned in Section 7.1 that, due to the formation of a series of highly reactive intermediate ions and complexes (ion pairs, etc.), a large number of products are formed in the majority of "direct" deaminations of alkylamines and deaminations via precursors. Therefore, deaminations do not display the same importance for syntheses as for mechanistic studies. There are very few exceptions. The most important are the methylation of alcoholic and carboxylic OH groups with diazomethane. This reaction is used for cases where high yields and mild conditions are required, e. g., for expensive hydroxy compounds like certain natural products. The methyl ester formation as well as the methylation of phenols does not need an acid catalyst as these substrates catalyze themselves the dediazoniation. For ether formation an acid catalyst, e. g., HBF4, is added (except from phenols). Typical is the methylation of 3/Miydroxycholestane, which proceeds in dichloromethane in 95 % yield, as shown in the Organic Syntheses method of Neeman and Johnson (1973). Analogously, ethers can be transferred in dialkylmethyloxonium salts, as described in another Organic Syntheses procedure (Helmkamp and Pettitt, 1973) for the formation of a trimethyloxonium salt obtained

296

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

by the 0-methylation of dimethyl ether. All these methods, however, are useful only for methylation, as higher diazoalkanes than diazomethane give too many by-products (hydrogen shifts, alkene formation etc.). Because of the toxicity and the relative instability of diazomethane, this methylation reagent has been replaced in recent years in many cases by (trimethylsilyl)diazomethane. The latter is now commercially available as a 2 M solution in hexane (Aldrich). Aoyama and Shioiri (1990) described a general method for the methylation of alcohols in the presence of esters, ketones and CC double bonds. Methyl carboxylates are quickly obtained from carboxylic acids with this reagent in the presence of methanol (Hashimoto et al., 1981; information from Aldrich, 1994). Also quite important and useful is the retentive hydroxy- and halo-de-amination of a-amino acids (see below). Our discussion of the influence of counterions, (so-called) inert molecules, and the solvent on the configuration of substitution products in deamination (Sect. 7.3) showed clearly that the immediate neighborhood of the reacting C-atom is of decisive importance. It is, therefore, not surprising that nucleophilic substituents of the reacting amine influence the overall process significantly. It has been known for a long time, going back at least to the early work by Ingold's school (Brewster et al., 1950; see Ingold's book, 1969, p. 538), that deamination of a-amino acids affords a-hydroxy acids with retention of configuration. The observed retention is the result of a double inversion with the chiral a-lactone as intermediate (Scheme 7-41).

(7-41)

Olah et al. (1979) and Barber et al. (1982) showed that in situ diazotization and fluoro-de-diazoniation of a-amino acids in hydrogen fluoride-pyridine (7:3) is an interesting method for the synthesis of a-fluorocarboxylic acids. In the presence of KCI or KBr the corresponding chloro- or bromocarboxylic acids, respectively, are found in excellent yields by using the less acidic 48:52 hydrogen fluoride-pyridine system (Olah et al., 1983). The stereochemistry of chloro-de-diazoniations was investigated by Koffenhoefer and Schurig. In an Organic Syntheses process these authors (1988) describe that (5)-2-chloroalkanoic acids of high enantiomeric purity can be obtained from (S)-2-amino acids. All these results are consistent with a double inversion. If the C(a)-atom of the a-amino acid 7.136 is substituted by a second alkyl residue, or if the substituent R is branched further, the pattern of deamination products is much more complex, as the example of (S)-terMeucine (7.137; Quast and Leybach, 1991) demonstrates (Scheme 7-42). The deamination of L-glutamic acid (7-43) is useful because it leads to the pure (+)-CS')-y-butyrolactone-y-carboxylic acid (7.138, (5)-tetrahydro-5-oxofuran-2-car-

7. 7 Synthetic Applications of Deamination Reactions

S

(CH3)3C°'

+

H

OH

7.137

(CH3)2Cx

(CH3)3C°'

291

X

H

C. XCOOH

(CH3)2Cx +

.Cx H° CH3

K

10%

^OOH

>- C \ CH3

6%

boxylic acid), which is an intermediate for pheromone syntheses (Gringore and Rouessac, 1990, an Organic Syntheses reaction; for related pheromone syntheses and for the stereochemical mechanism with overall retention, see Smith and Williams, 1979). As shown in Scheme 7-43, the mechanism presumably involves anchimeric assistence of the a-carboxy group in the decomposition of the diazonium ion, leading to a labile a-lactone which rearranges into the (+)-(5)-y-butyrolactone-y-carboxylic acid. HOOC

HOOC

HNOp

^c

->•

-H+

COOH

(7-43)

H COOH

7.138

a-Lactones are intrinsically reactive and, therefore, generally unstable. Only few a-lactones have been observed since Wheland and Bartlett (1970) identified di(teAt-butyl)acetolactone at — 60 °C. Stereochemical investigations of products supported oxaspiropentanone (7.139) as intermediate in the diazotization of 1-aminocyclopropanecarboxylic acid (7-44; Pirrung and Brown, 1990).

'^'^

'^

''

NH3+

7.139

products

(7-44)

298

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

The bis-deamination of L-lysine with pentacyanonitrosyl ferrate (sodium nitroprusside, see Sect. 2.3) leads in relatively good yield (30%) to L-piperidine-2-carboxylic acid (Kisfaludy et al., 1982) whereas in older multistep processes only 6-11% was obtained. For many decades, ring expansion and contraction was dominated by deaminations of cycloalkylamines by nitrosating reactions, as discovered by Demjanov and Lushikov (1903) and named after Demjanov. The Tiffeneau reaction (Tiffeneau et al., 1937) is a nitrosation of a 1,2-aminoalcohol. Today, one uses often the name Demjanov-Tiffeneau reaction (or Tiffeneau-Demjanov) for both processes. In the second half of this century a number of different ring expansion and contraction methods were found. This becomes evident in the recent monograph of Hesse (1991), in which there is only one reaction scheme related to the Demjanov-Tiffeneau reaction proper. Other processes, such as ring expansion by adding diazomethane to a cyclic compound with one or more double bonds forming a bicyclic compound with a cyclopropane ring, either in a 1,3-dipolar addition followed by azo extrusion of the pyrazoline intermediate (see Sect. 6.5), or by forming methylene as synthon for cyclopropanation (Sects. 8.4-8.5), are mentioned in the section with the title "Tiffeneau-Demjanov Rearrangement" in the book by Hesse. They are useful methods for ring enlargement, but they have nothing in common with these name reactions. For an extensive review on the Demjanov-Tiffeneau reactions one has to rely, therefore, on the old report of Smith and Baer (1960), on the monograph of Gutsche and Redmore (1968), and on shorter discussions by Wulfman (1978, p. 298) and Whittaker (1978, p. 627) in the Patai series "The Chemistry of Functional Groups". The review of Krow (1987) on one carbon ring expansions of bridged bicyclic compounds contains examples of the Tiffeneau reaction. Krow uses the names of both reactions, however, in a much broader sense (see below). As a rule, ring expansions are favored in small rings and in bicyclic systems, because these compounds are characterized by high ring strain (Berson and Reynolds-Warnhoff, 1964). This rule is, however, not general as the comparison of the Demjanov reaction of cyclohexylmethylamine (Smith and Baer, 1952; 7-45) and of cyclopropylmethylamine (Roberts and Mazur, 1951 a; see Scheme 7-38 in Sect. 7.5) shows. Yet, the yield of 47% cyclobutanol in 7-38 is significantly larger than that of cyclopentanol in the deamination of 2-cyclopropylethylamine (Cartier and Bunce, 1963). The later ring expansion by two CH2 groups by a 1,3-alkyl shift is, of course, not a Demjanov reaction. A similar 1,3-alkyl shift was found by Meikle and Whittaker (1974) in the deamination of eftdo-myrtanylamine (7.140, Scheme 7-46). In spite of competing 1,2-alkyl and 1,2-hydride shifts, the 1,3-alkyl shift results in release of the highly strained four-membered ring. The expected 1,2-alkyl shift expands the six- to a sevenmembered ring and results, therefore, in little release of strain. A hydride shift has no influence on the bicyclic carbon skeleton.

CH2NH2

^ |

)

^J

66%

OH + ( \

} /

33%

CH2OH + ( \

X^ (7-45) / OH

1%

7.7 Synthetic Applications of Deamination Reactions

299

(7-46) /.—*"* + ~

f^

^\y

^x"^

^^V

CH2NH2 OAc

OAc

9%

7.140

11%

With respect to cyclobutanol, we draw attention to two newer synthetic methods, which were described more recently by Krumpolc and Rocek (1990) and by Salaiin and Fadel (1990) in Organic Syntheses. Both are simple acid-catalyzed ring expansions of cyclopropylmethanol that give cyclobutanol in ca. 80% and 51% yield, respectively. They demonstrate the advantage over the main weakness of deaminations, namely the formation of various by-products which are found in most deaminations. The Tiffeneau reaction is used to form ring-enlarged ketones, as the examples 7-47 show for the synthesis of cyclooctanone (7.142, n = 7; yield 61 %, Blicke et al., 1953) and cycloheptanone (7.142, n = 6; yield 40-42%, Dauben et al., 1963). -NH2

-Ox

,CH2-N2+

HNO2 >— -H+

"(CHa)/

(7-47)

(CH,)^

Obviously, the zwitterion 7.141* is the characteristic intermediate for the Tiffeneau rearrangement. This can also be obtained in the reaction of a ketone with diazomethane (7-48) and leads, therefore, also to the next higher homolog of the starting cycloalkanone (see also Sect. 9.1). * Most authors do not assume the formation of a zwitterion, but of a cation for this intermediate. We think that a zwitterion is more likely here than only in the next step.

300

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

(7-48)

This reaction is due to the nucleophilicity of the diazomethane C-atom (see Sects. 4.4 and 9.1). If diazo compounds have to be used that are less nucleophilic, e.g., diazoacetates, the reaction proceeds smoothly in the presence of Lewis acids such as BF3 and SbF5 (Dave and Warnhoff, 1983). We shall discuss such reactions in more detail in Section 9.1. As the reagents used for the process in Scheme 7-48 are different from those in Tiffeneau reactions, and the intermediate 7.141 is not stable enough to be detectable, this process should not be called a Tiffeneau rearrangement. Reactions 7-47 and 7-48 are obviously not restricted to diazonio substituents as leaving groups. Analogous reactions have often been conducted with halogenomethyl- and other substituted methylcycloalkanols (see review of Larock, 1989, p. 630). Ring enlargements of cycloalkanones were also reviewed by Burke and Grieco (1979), Smith and Dieter (1981), Black (1983), and Anderson (1985). Ring contractions in deaminations have also been found, but far less frequently than expansions. An example was mentioned already in Section 7.5: Roberts and Mazur (1951 a) found that cyclopropylmethylamine and cyclobutylamine yield cyclopropylmethanol and cyclobutanol in approximately the same yields (see Scheme 7-38). The stereochemistry of the deamination of stereoisomeric 2-amino-4-(te/t-butyl) cyclohexanols (7-49) was studied by Cherest et al. (1965). The reaction depends obviously on which group is antiperiplanar to the amino group, but with conformationally mobile systems, no general conclusions were possible. As the discussion in the preceding sections demonstrated that in many deaminations "free" carbocations or their ion pairs of various types are intermediates, other reactions involving carbocations may be also feasible with alkylamines or their

7.7 Synthetic Applications of Deamination Reactions

301

derivatives under deamination conditions. White et al. (1988, 1995) studied this question by applying the TV-nitroso amide method of deamination for Friedel-Crafts alkylation of benzene, toluene, pyrrole, and furan*. As alkylating reagents, Nnitroso sulfonamides (White et al., 1988), JV-nitroso amides of three carboxylic acids and four related types of deamination precursors (two of them forming N2O rather than N2) were used. The alkylating group was benzyl in most cases. The reactions were run in the aromatic hydrocarbons as reagents and solvents that gave better results than the use of a cosolvent like CD3NO2 or CDC13. The expected alkylated aromatic hydrocarbons were indeed found, but only in low yields (6-19%)**. In the reaction with toluene, the isomer distribution is characterized by a much higher fraction of meta-product (14-21 %) relative to classical Friedel-Crafts reactions (3-6%). The /7
RONO CH3COOH '

I

|l

11^1

(7-50)

* The analogous reaction of an aromatic TV-nitroso amide (7V-nitrosoacetanilide) with benzene forming biphenyl was discovered by Bamberger in 1897. ** The authors give yields in percent for the Friedel-Crafts product and for the ester, i. e., the reaction product of the carbocation with the anion formed from the nitroso compound. The sum of these two figures is 100%. It seems doubtful that the material balance is really as perfect! *** Other products (see text) are not given in (7-50) and (7-51).

302

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

CH3

7.146 (31%)

7.8 Summary and Outlook (kindly contributed by Wolfgang Kirmse, Ruhr-Universitat, Bochum, FRG) In the preceding sections, many deamination reactions have been reviewed, some of them in detail. The discussion may have left the impression of great diversity and, occasionally, ad hoc explanations. Therefore, it will be appropriate to extract some general principles and guidelines. The key to understanding deamination reactions is the pivotal role of diazonium ions (Streitwieser and Schaeffer, 1957 b) (Scheme 7-11). Although reactants and products are manifold, diazonium ions mark the crossroads at which all reaction paths merge. Streitwieser's hypothesis, a stroke of genius at its time, has since been supported by a growing body of evidence. In favorable cases, aliphatic diazonium ions have been detected spectroscopically (Mohrig and Keegstra, 1967; Mohrig et al., 1974; Berner and McGarrity, 1979; McGarrity and Cox, 1983). In the past, there has been concern that diazonium ion precursors might contribute to product formation. However, recent kinetic studies (Hovinen and Fishbein, 1992; Hovinen et al., 1992; Finneman et al., 1993) have confirmed that the dissociation of (Zi)-diazenols proceeds stepwise (R-N 2 -OH^R-Ni h + HO~) rather than in a concerted fashion (R-N 2 -OH -»R + + N2 + HO~). Moreover, the reaction rates of diazenols are but slightly affected by nucleophiles; these observations exclude bimolecular displacement (X~ + R-N 2 -OH-»X-R + N2 + HO~). Thus, diazenols (and, by inference, their esters) do not mimic the reactions of diazonium ions. The ubiquitous equilibration of diazonium ions with diazo compounds is a side reaction that leads to incorporation of deuterium from deuterated solvents. As a rule, the intervention of diazoalkanes does not open additional routes to products. There are rare examples of extremely labile diazo compounds (e.g., diazocyclopropanes: Kirmse and Jendralla, 1978; Kirmse and Hellwig, 1982; Kirmse et al., 1983, 1985), decomposition of which may induce carbenic reactions. The chemistry of aliphatic diazonium ions is most logically described in terms of Streitwieser's "compressed energy scale". Streitwieser and Schaeffer (1957b) pointed

7.7 Synthetic Applications of Deamination Reactions

303

out that the small activation barrier of nitrogen extrusion from aliphatic diazonium ions brings the rates of several competing processes closer together. The competing processes are conveniently classified as solvolytic displacement (&s), unassisted ionization (£c), and neigboring group participation (&A, see Scheme 7-14). As a consequence of the compressed energy scale, the relative contributions of these diverse mechanisms are less substrate-dependent for diazonium ions than for halides or sulfonates. Nevertheless, some limitations remain. Complete inversion of configuration has been demonstrated for methanediazonium ion (Gautier, 1980) and alkane-1-diazonium ions (Brosch and Kirmse, 1991), thus excluding the intermediacy of primary carbocations. On the other hand, solvolytic displacement (k§) appears to be negligible with tertiary alkanediazonium ions. A maximum of competing processes is normally observed for secondary alkanediazonium ions. It should be recalled that even the analogous halides and sulfonates represent "borderline" cases in solvolytic reactions. The effect of structural variation is most clearly seen for dediazoniation reactions in polar solvents, preferably water. Less polar solvents, such as acetic acid, play a dual role, enhancing solvolytic displacement, with inversion of configuration, as well as ion pairing, leading to retention (Banert et al., 1986). The prevailing reaction path depends on the relative stability of the diazonium ion and carbocations. Thus, aarylethanediazonium ions react with predominant retention of configuration. The formation of resonance-stabilized benzylic cations facilitates the decay of diazonium ions pairs to give carbocations with frontside orientation of the counterion. In contrast, longer lived alkane- and cycloalkanediazonium ions prefer inversion of configuration because the extrusion of nitrogen is assisted by the solvent. In order to focus on ion pairing, the thermolysis of nitroso amides in nonnucleophilic solvents is the method of choice (Huisgen and Ruchardt, 1956; White et al., 1992b and earlier papers). Although these studies of ion pairing are interesting in their own right, the results apply only to a rather narrow range of reactants and reaction conditions. In particular, dediazoniation reactions in water are not significantly influenced by ion pairing. Admittedly, the yields of aqueous nitrous acid deamination reactions are often poor, owing largely to secondary reactions of alkyl nitrites. However, these complications can be avoided by means of alternative methods, such as photolysis of toluenesulfonylhydrazone sodium salts or base-induced cleavage of nitroso amides. Neighboring group participation (&A) is worthy of a special comment. As a rule, £A processes provide low energy reaction paths that are more prominent in solvolyses of sulfonates than in deamination reactions. Aryl participation in the 2-aryl-l-methylpropyl system (Cram and McCarty, 1957) may be cited as a textbook example. However, if neighboring group participation is associated with an increase in strain energy, the energetically more demanding &A process will be accentuated by the better leaving group. Therefore, the 7-bridged norbornyl cation (7.108, Kirmse and Siegfried, 1983; Kirmse, 1986) and the bridged 4-cycloheptenyl cation (Kirmse et al., 1984) are accessible from appropriate diazonium ions, but not from sulfonates. These cases should not be regarded as "exceptional", since they fit nicely into the framework of current theory. Excessively strained intermediates, such as 7.126, cannot be generated even from diazonium ions (Bentley et al., 1988).

304

7 Dediazoniation Reactions Involving Diazonium Ion Intermediates

During the past decades, substantial progress has been made in validating dediazoniation mechanisms. The implications of the excellent leaving group N2 are now well understood, at least in a qualitative sense. Unsolved problems notwithstanding, the field has reached a state of maturity. Although mechanistic evaluations have profited greatly from advances in methodology, improved control of selectivity has rarely been achieved. Synthetically useful dediazoniation reactions remain limited to cases of powerful neighboring group participation, such as retentive deamination of a-amino acids and the Demjanov rearrangement, as well as to the classical methylations of alcohols and carboxylic acids (Sect. 7.7).

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

8.1 Introduction to General Carbene Chemistry As shown in the preceding chapter, a characteristic feature of aliphatic diazo compounds is that a diversity of reaction intermediates is formed by dediazoniation. Alkanediazonium ions and ion pairs containing carbocations are generated mainly in protic media (Chapt. 7). The diazo reactions in this chapter are characterized by processes run either in the gas phase, in relatively inert matrices, or in — typically, but not exclusively — aprotic and comparatively apolar solvents, either thermally or photolytically or with transition metal catalysis of various types. The metastable intermediates are carbenes (RR'C:), i.e., neutral, apparently divalent, carbon compounds*, or their transition metal complexes (coined carbenoids, see later in this section). It is interesting to recall that the synthesis of a compound that we now call a carbene, namely methylene (H2C:), was already attempted in the early 19th century, i.e., before the tetravalency of carbon was established. Dumas (1835) and Regnault (1839) thought then that it should be possible to obtain a compound consisting of one carbon and two hydrogen atoms by dehydration of methanol (a compound of which only the atomic ratio 1C:4H: 1O was then known)** Analogously to the ion pairs involving carbocations mentioned above, diazo compounds are not the only source of carbenes, as they can also be obtained as metastable intermediates by other methods than by dediazoniation of diazoalkanes (see below). At the end of the 19th century, structural organic chemistry was developed to such an extent that it was realistic to attempt the synthesis of a compound such as methylene because then at least two compounds with formally divalent C-atom (more precisely, dicoordinate carbon) were known, namely carbon monoxide and hydrogen isocyanide. A suggestion of Geuther in 1862 can also be mentioned, as he speculated that :CC12 might be formed in the alkaline hydrolysis of trichloromethane (chloroform), a suggestion shown to be correct 88 years later!***. An * In the 1979 edition of the IUPAC Nomenclature of Organic Chemistry the term "radical" was used for several items including explicitly carbenes, and "free radicals", i.e., particles with an odd number of electrons (Rule C-81). In the Revised Nomenclature for Radicals, Ions, and Related Species (IUPAC, 1993), the adjective "free" is not used for the second group of particles. Therefore, the term "radical" should no longer be used for carbenes. ** Mesomeric formulations were, of course, also unknown at that time! *** For further examples from the 19th century see Kirmse (1969, p. 6). Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Veriagsgesellschaft mbH ISBN: 3-527-29222-5

306

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

optimistic statement of Nef, published in 1895 on an investigation on cyano compounds (p. 359), was, therefore, not as naive as we may consider today: "Es wird nun meine nachste Aufgabe sein, das Methylen oder Derivate desselben... darzustellen" (My next goal will be to synthesize methylene or derivatives of it). A century ago, Nef could not know, by any means, how unstable methylene actually is and how much theoretical and (indirect) experimental work was necessary to obtain reliable information on its structure (bond length, bond angle) and its energy of formation! In fact, reactions involving methylene and other carbenes, as metastable intermediates, were studied successfully in the first half of this century, e.g., by Staudinger and Kupfer (1912), who obtained ketene (H2C = C = O) when they pyrolyzed diazomethane in the presence of CO, or by Meerwein et al. (1942), who discovered the insertion of the methylene group of diazomethane into O-H and C — H bonds of alcohols. Modern carbene chemistry started, however, in a rather unusual way when Hine (1950) conducted a kinetic study of the alkaline hydrolysis of trichloromethane (chloroform). He proposed a two-step a-elimination involving CC12 as an intermediate. The result of this mechanistic study was unusual because it opened a new field of synthetic organic chemistry, whereas, in general, such studies improve our understanding of fields already known from synthetic work. Hine's dichlorocarbene was subsequently applied to a cyclopropane synthesis by Doering and Hoffmann (1954, see later in this section). As mentioned by Doering and Knox (1956, footnote 9), the present meaning of the name carbene was "collaboratively conceived by Doering, Winstein, and Woodward in a nocturnal Chicago taxi and later (1951) delivered diurnally in Boston". Carbenoids have been defined by Closs and Moss (1964) as "intermediates that exhibit reactions qualitatively similar to those of carbenes without necessarily being free divalent carbon species". As mentioned already, this definition is applicable first of all to transition metal complexes of carbenes. Today, the a-elimination of hydrochloric acid from chloroalkanes (review: Kirmse, 1965) is the second most important method for the formation of carbenes, following the decomposition of diazo compounds. Two other methods, more closely related to the formation of carbenes from diazoalkanes, are the photolysis of ketenes (8-1, the CO formed is isoelectronic with N2) and the decomposition of diazirines (reviews: Liu, 1982, 1987). Some other methods are used only occasionally, e.g., the decomposition of certain cyclopropanes (review: Hoffmann, 1971, 1985) and carbene formation starting from metal-carbonyl complexes with Grignard reagents (so-called Fischer carbene complexes; Fischer and Maasbol, 1967, and later investigations by Fischer's group; reviews: Brookhart and Studabaker, 1987; Helquist, 1991 b) and from mercury complexes (Schollkopf and Gerhart, 1967). It is not within the scope of this book to give detailed information on these and some other synthetic routes to carbenes (see monographs and reviews on carbenes mentioned at the end of this section, and Scheme 10.5, p. B 516, in Cary and Sundberg's book Advanced Organic Chemistry, 1990). :CH2 + CO

(8-1)

8.1 Introduction to General Carbene Chemistry

307

Although Skell and Woodworth (1956) and Skell and Garner (1956) postulated that carbenes might be found in singlet and triplet states (see Sect. 8.3), it took a long time until the knowledge on structures of carbenes and of methylene, in particular, was secured. In 1975, Caspar and Hammond published (p. 223) a table listing theoretical treatments of carbene structure and energetics — starting with a classic paper of Mulliken (1932), the table contains 16 pages! * That amount of scientific work is clearly proportional to the amount invested for the elucidation of the nonclassical carbocation discussed in Section 7.5. There is, however, an important difference. The latter problem requires, at least in principle, a yes or no answer to the question whether a nonclassical carbocation exists at all. For carbenes, the existence as such was not doubted — the aim of the search was to find various numerical parameters of their structures. Staying with the parent compound methylene for the moment, it seems that, after Caspar and Hammond compiled their table in 1975, the results obtained later were no longer fundamentally doubted**. The controversies before 1975 were concerned mainly with the question whether the ground state is a singlet or a triplet and whether these two molecules display a linear or a bent arrangement of the three atoms. After 1975, there is almost general agreement that the bond angle is 136° in the triplet and ca. 102° in the singlet, and that the triplet is the ground state (T! = 3B!) with an excited singlet state (S0 = ^i) and a doubly excited singlet state (Si = lEii Fig. 8-1), all representing discrete entities with quite a small SO/T! energy splitting (ca. 38 kJ mol"1, see Lengel and

State energies

Fig. 8-1. Electronic states of methylene.

* For the early history of carbene chemistry, see also Skell (1985). ** This is evident from analogous tables published by Wentrup in 1979 (p. 140) and in 1984 (p. 164): No basically different results were published after 1975. See also the remarks of Moss and Jones (1981, p. 60 and 1985, p. 46) and for nonempirical calculations, the review of Minkin et al. (1989, table 2, p. 625EE).

308

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

Zare, 1978). This value was experimentally verified by several authors (see e.g., Hayden et al., 1983; Kellar et al., 1983; Leopold et al., 1984). In the singlet (S0), the two nonbonding electrons lie in the H — C — H plane (sp2 orbital), whereas in the triplet they occupy the sp2 and the p orbital. Knowledge on the SQ —T! energy gap of methylene was also improved significantly after 1975, particularly since nonempirical methods were used more extensively. A very informative compilation of values calculated using various computational schemes with minimal-to-very-large basis sets was published by Minkin et al. (1989, Table 2; see also Shavitt, 1985, and Schaefer, 1986). The same authors found that, among semiempirical methods (CNDO, INDO, MINDO/2, MINDO/3 and MNDO), preference should be given to the MINDO/3 method. Triplet methylene was directly observed first by Skell and Wassermann's groups (Bernheim et al., 1970; Wassermann et al., 1970) using ESR spectroscopy. After a search lasting more than ten years, Herzberg and Shoosmith (1959; see also Herzberg, 1961, 1966) recorded the UV spectrum of the singlet in the gas phase. The singlet was produced as primary product by photolysis of diazomethane. This result is expected on the basis of spin conservation. The singlet decays into the triplet, which is more stable. In solution, the singlet is trapped by almost any molecule before it can undergo intersystem crossing to the triplet. Trapping takes place either by chemical reaction (mainly bond-insertion processes, see Sect. 8.5), or by (physical) collision with molecules that are almost inert to reactions with methylene. Such molecules favor intersystem crossing to the triplet (e.g., hexafluorobenzene or perfluorohexane; see Turro et al., 1987)*. Methylene reacts, however, in a nitrogen matrix at 77 K with N2, as shown in a classical investigation by Moore and Pimentel (1964 d). Diazomethane was also detected by Maier and Reisenauer (1986), resulting from the irradiation of dihalogenomethanes X —CH 2 I (X = I, Br, Cl) with light of wavelength 313 nm at 13 K in a polyethylene film in the presence of N2, and by O'Gara and Dailey (1992) in the reaction of bromo-trifluoromethyl-carbene with N2 in an argon matrix at 12 K (see Scheme 8-9). At room temperature, however, Zollinger and coworkers (Grieve et al., 1985) could not detect N2 exchange of various 15N-labeled diazoalkanes with unlabeled N2 under reaction conditions leading to carbene formation. The difficulties in the direct recording of carbene spectra were overcome during the last two decades, first by pulse methods, which allow creation of high concentrations of carbenes during a short time interval, and second by the isolation of carbenes in low-temperature matrices (review: Zuev and Nefedov, 1989). The spectra obtained by the latter technique and those by pulse methods at room temperature were shown to be the same. In the 1980's and 1990's, over two dozen substituted derivatives of methylene were investigated experimentally or by theoretical methods with respect to their structure and the S0 —T! energy gap. Russon et al. (1992) have recently discussed singlet-triplet energy separations. At an early date, Hoffmann's group (Hoffmann et al., 1968; Gleiter and Hoffmann, 1968) introduced principles of the influence of * For a recent investigation on carbene-collision processes in the gas phase, see Garcia-Moreno et al. (1993) and the large number of references mentioned there.

8.1 Introduction to General Carbene Chemistry

309

substituents on the stability of the singlet and the triplet, and on their energy gap on the basis of EHMO calculations. n,7i-Electron-donor substituents (halogens, NH 2 , OH) and 7T-acceptor substituents stabilize the singlet to such an extent that it becomes the ground state. Experimental values, for instance, are —63 (Scuseria et al., 1986) and —237 kJ mol"1 (Koda, 1982) for mono- and difluorocarbene, respectively. Theoretical results (Scuseria et al., 1986; Carter and Goddard, 1987; Cai, 1993 and references there) agree with the experimental values within 8 kJ mol"1. The elegant ab initio techniques used by Schaefer (Schaefer, 1986; Scuseria et al., 1986) are probably still beyond computational and financial constraints for arylsubstituted carbenes*. Li and Schuster (1988) found, however, in a comparative study of 21 such carbenes with three semiempirical methods (MNDO, MINDO/3, AMI) that, in general, MINDO/3 gives the best correlation with experimental values; the worst result being that for diphenyl carbene (26 kJ mol"1 higher than the experimental value). On the other hand, for xanthenylidene (8.1) a singlet ground state is obtained by these calculations. This result is in agreement with experiment (Dewar et al., 1984).

An interesting case of a carbene is nitromethylene (HC —NO 2 ), with respect to synthesis, reactions, and theory. Syntheses were attempted since the early 1970's, but the compound has been detected only recently by O'Bannon et al. (1992). Nitromethylene was one of the carbenes included in the early EHMO calculations of Hoffmann et al. (1968). The most comprehensive theoretical study was carried out by Bolton and Schaefer (1993) on an ab initio level. The most interesting aspect of this calculation is the suggestion that the singlet is lower in energy than the triplet by about 29 kJ mol"1** We discuss qualitative and quantitative aspects of singlet and triplet carbene reactions in Section 8.3 and 8.4. Is it possible to stabilize carbenes by suitable substitution to the extent that they are stable enough to be isolated? In CO and in isocyanates, which are structurally related to carbenes, the heteroatom compensates for the electron deficiency on the C-atom. Although an organic chemist would not intuitively consider these molecules as carbenes, they undergo some reactions that are typical for carbenes. There are, however, at least four groups of clearly "organic" compounds with a carbene-like C-atom bonded to two heteroatoms, namely 8.2-8.7. They were synthesized in various ways by Wanzlick and Schickora (8.2; 1960, 1961), by Quast and * For a general review on arylcarbenes, see Schuster (1986). ** Bolton and Schaefer's paper contains extensive references to previous experimental and theoretical investigations on nitrocarbenes (R - C - NO2).

310

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates C6H5 N

r^

TT^ \

/

w

\\

P —C —Si(CH3)3

N

C6H5 8.2

8.5

8.3

8.4

8.6

R = CH3

8.7

R = CD3

Hiinig (8.3; 1964, 1966), by Bertrand's group (8.4; Igau et al., 1988), and by Arduengo et al. (8.5; 1991). For compound 8.5, an X-ray crystal structure determination was carried out, in addition to 13C NMR spectroscopy. Arduengo et al. (1992 a, 1992b) found other stable imidazol-2-ylidenes besides 8.5, e.g., 8.6 and 8.7. All these compounds are characterized by typical carbene reactions (see review of Regitz, 1991, and papers of Arduengo et al., 1991, 1992a, 1992b, 1994a, 1994b). The crystal structures of 8.5 and five other imidazol-2-ylidenes (Arduengo et al., 1992 a, 1994) show that the N —C —N bond angle at the carbene center is 101.2-102.2°, i.e., the angle calculated for S0 of methylene. Assuming, therefore, a singlet ground state for 8.5 and its five derivatives, it is likely that the stability of the singlet relative to that of the triplet is due to the increased ring strain of the latter as a result of an N(l) —C(2) —N(2) angle that is probably similar to that of methylene (136°, see above). This explanation has not been mentioned by Arduengo et al., but Dixon and Arduengo (1991) emphasize the electronic factors operating in the n- and o-framework. Ti-Electron donation into the carbene p orbital occurs from the electron-rich system N — C = C — N, decreasing electrophilic reactivity of the carbene. Additional stability is to be attained from the o-electon-withdrawal effect on the carbene C-atom by the more electronegative N-atoms. The steric effect arising from two adamantyl substituents is probably of minor importance, as 1,3,4,5-tetramethylimidazol-2-ylidene (8.6) is also stable. In 1994 Arduengo et al. published a detailed neutron and X-ray diffraction study as basis for a determination of the distribution of electrons in its perdeuterio derivative 8.7. The results show that this compound is a true carbene with negligible ylide character.

8.1 Introduction to General Carbene Chemistry

311

In spite of the fact that reactions of diazo compounds via carbenes are discussed in detail in Section 8.3 and later in this chapter, products formed from carbenes in general are summarized briefly here because the subject of Section 8.2 (dediazoniation mechanisms of diazo compounds to carbenes) is based to a significant extent on investigations of their reaction products. This short synopsis is mainly based on historically important investigations, although it also contains reactions in which the carbene or carbene-like precursor is not a diazo compound, but, for example, an alkyl halide. The most important carbene reaction — mechanistically and for synthetic applications — is the cycloaddition to alkenes, i. e., the formation of cyclopropanes. This reaction was studied briefly by Buchner and Geronimus (1903) long before Hine's "rediscovery" of carbenes. They found ethyl 2-phenylcyclopropanecarboxylate in the reaction of ethyl diazoacetate with styrene. Besides the attention given by Staudinger et al. (1924), however, little attention was paid to that work, apart form the fact that it may be a 1,3-dipolar cycloaddition followed by an azo-extrusion (Sect. 6.5). The first clear case of a cyclopropanation via a carbene was presented by Doering and Hoffmann in 1954*. They added trichloro- or tribromomethane and a base to a nonaqueous solution of cyclohexene and obtained 7,7-dichloro- (or 7,7-dibromo)bicyclo[4.1.0]heptane (norcarane, 8-2).

— X3CH

^ X2C:

^

X2(Xn

I

(8-2)

Cyclopropanations will be discussed in Section 8.3. The reaction of carbenes with aromatic hydrocarbons is related to that with alkenes. Doering and Knox (1950, 1953) investigated this reaction using benzene as substrate even before their work with cyclohexene. They observed, however, ring expansion to give cycloheptatriene besides toluene (8-3, X = H). Norcaradiene as an intermediate was isolated only much later in the addition of dicyanomethylene

(8-3)

(X: see text)

* For earlier unpublished work of Doering and Knox, see Doering and Hoffmann (1954, footnote 10). In IUPAC nomenclature, Cyclopropanations are called ep/-methylene additions.

312

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

(X = CN in 8-3) by Ciganek (1967). A more generally applicable route to norcaradiene derivatives was realized by the Simmons-Smith procedure (1959) using CH2l2 and a Zn — Cu couple (which may be called a carbenoid reagent, yet in a somewhat broader sense than the term carbenoid is used today, see Sect. 8.7). The formation of toluene in the reaction of diazomethane with benzene (8-3) brings us to the second characteristic reaction of carbenes, namely insertion into single bonds, in this case into an sp2-C —H bond. Here again "prehistoric" examples (i.e., investigations before 1950) of Buchner and Meerwein are known (Buchner and Schulze, 1910; Buchner and Scholtenhammer, 1920; Meerwein et al., 1942), as well as early systematic work by Doering's group after 1950. Doering et al. (1956 a) found that the photochemical dediazoniation of diazomethane in pentane yields hexane, 2-methylpentane, and 3-methylpentane by insertion into sp3-C-H bonds at C(l), C(2), and C(3), respectively, at 15 °C in the ratio 49: 34:17, and at - 75 °C in the ratio 48 : 35 :17; i. e., at both temperatures very close to the statistical ratio of 50:33.3 :16.7 or 6:4:2. In other words, the very small temperature dependence and the product ratios indicate that the selectivity of the primary and secondary CH goups is essentially nonexistent. Tertiary CH groups (in 2,3-dimethylbutane) were found to be not much different. Diazomethane reacts with cyclopentane to give methylcyclopentane and no cyclohexane, i.e., no C —C bond insertion was observed. Doering and Knox (1956) investigated the thermal and photolytic dediazoniation of diazoacetate with pentane and with 2,3-dimethylbutane obtaining similar results; only a slight preference for tertiary CH group insertion was found. Shortly afterwards, Frey and Kistiakowsky (1957) and Frey (1958) confirmed the extremely low selectivity in the gas phase, but they also found abstraction products, according to Scheme 8-4. The intermediacy of radicals could be shown in the presence of radical scavengers, such as O2 and NO, where such abstraction and recombination products were not found, but only the insertion products were obtained. R—X

+• R' + *CH2X

+• R—CH2X + R—R +

XH2C —CH2X

(8-4)

Insertion into O — H bonds of alcohols occurs faster than into their C — H bonds. The corresponding ethers are, therefore, easily detectable. Carbenes are also subject to rearrangements. Migration of hydrogen (8-5; Wilt and Wagner, 1964), and alkyl and aryl groups (8-6; Philip and Keating, 1961) results (partly via more stable carbenes) in various products. The Wolff rearrangement (Wolff, 1902; see Sect. 1.1, Scheme 1-3, and Sect. 8.6) is an important carbene rearrangement based on diazo ketones. Intramolecular C — C bond cleavage in photolyses of diazoalkanes was observed in compounds with strained rings adjacent to the carbene C-atom, e.g., in the photolysis of cyclopropylphenyldiazomethane where 1-phenylcyclobutene is one of the products (8-7; Moss and Wetter, 1981; Celebi et al., 1993). Carbenes are the conjugate bases of carbocations, as shown in 1963 by Kirmse for the photolysis of diphenyldiazomethane in methanol. This work also provides early

8.1 Introduction to General Carbene Chemistry

313

(8-5)

38%

H3C

C6H5

50%

hv

-

H3C

CH3

9%

16%

CH2 0 CH 2

H C

3

41%

^-^

(8-7)

evidence for the dependence of the quantum yield on the wavelength of the irradiation: The quantum yield was found to be higher with UV light of the second absorption maximum of diphenyldiazomethane (294 nm) than with visible light corresponding to the first maximum (526 nm). In the first 25 years of modern carbene chemistry (since Hine's investigation, 1950), a vast number of monographs and reviews have been published on this subject: In the volumes on diazo compounds of the Patai series, Ando (1978) lists 31 references of this type! During the following 18 years, however, this number decreased considerably. At the borderline of these periods, the two books of Kirmse (1969, 1971) and those edited by Jones and Moss (1973) and by Moss and Jones (1975) were published, followed later by three progress reports of the same authors (Moss and Jones, 1978, 1981, 1985). There are two relatively new reviews by Minkin et al. (1989) and Frey (1991) which focus on theoretical and reactivity aspects of carbenes *. The review of Minkin et al. is part of a series of review papers on carbenes published in Russian Rev. Chem. (Nefedov, 1989). Selectivity of carbenes in cyclopropanation is the subject of short reviews by Moss (1980, 1989). The most recent approach to theoretical evaluations of carbene reactions and products was published by Helson and Jorgensen (1994) on the basis of Jorgensen's program CAMEO (computer-assisted mechanistic evaluation of organic reactions, see Jorgensen et al., 1990). Helson and Jorgensen claim that their evaluations cover all reactions of carbenes and carbenoids. In our opinion, experience in the coming years is necessary to comment on this claim, if we consider the wide variety of reactions * Unfortunately, the review of Frey is only published as a conference report.

314

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

and dependence of products on reaction conditions, catalysts in carbenoid reactions described, in part only, in this chapter. There are two volumes of Houben- Weyl on carbenes (Regitz, 1989). The chapters on acyclic carbenes (Zeller and Gugel, 1989), arylcarbenes (Wentrup, 1989), and alkylidenecarbenes (Stang, 1989) are particularly important for the scope of this book. There has been no comprehensive monograph on carbenes since the books of Kirmse, Jones, and Maas were published in the early 1970's * Does this development indicate a decrease in interest in carbene chemistry? Not at all! One might even say that it seems that the enormous increase in the number of investigations on carbene reactions, particularly with the help of complex rhodium and related metal catalysts, makes it difficult to write a book on all aspects of carbene chemistry. The catalytic procedures for metal -carbene transformations from aliphatic diazo compounds are now the most important tool for cyclopropanations and related processes in organic synthesis. We shall mention reviews on that subject in Sections 8.7 and 8.8. Nitrenes are the nitrogen analogs of carbenes. The most common method for their formation is basically the same as that of carbenes from diazoalkanes, namely thermolysis or photolysis of azides (8-8).

Aorh

%

R— N +

N2

(8-8)

R— N— N=N

Nitrenes are also highly reactive species. Much less is known about their structure and reactivity compared with that of carbenes. Besides C-nitrenes, N-, O-, and sulfonyl nitrenes are also known (reviews: N- and O-nitrenes: Kuznetsov and loffe, 1989; sulfonyl nitrenes: Abramovitch and Sutherland, 1970). There are two monographs on nitrenes, edited by Luvowski (1970) and by Scriven (1984), and reviews by Luvowski (1978, 1981, 1985) and by Scriven (1982). Nitrenes are not included in this book. Silylenes, however, (SiH2, SiXY) will be mentioned briefly in Section 8.3.

8.2 Formation of Carbenes and Carbenoids by Dediazoniation of Diazoalkanes As already reviewed briefly in Section 8.1, carbenes can be formed starting from various precursors. In this section, we shall discuss various methods based on diazo compounds. More than twenty years ago, the review on diazoalkane-based carbene We see a clear difference between a monograph and a compilation like Houben-Weyl.

8.2 Formation of Carbenes and Carbenoids by Dediazoniation of Diazoalkanes

315

chemistry (Baron et al., 1973) covered half of the carbene monograph edited by Jones and Moss. The rapid development of metal-carbene chemistry (carbenoids, see below) since the 1970's lead to a further increase in investigations based on diazoalkanes. It must be emphasized, however, that some other reactions were historically important for the concept of carbenes (e.g., a-elimination of haloalkanes, see Sect. 8.1), or are methods of choice for specific products (e.g., dihalocarbenes) or for specific processes of carbene formation, e. g. , gas-phase reactions of methylene formed from ketene, as shown in the work of Wagner's group (Bohland et al., 1986; Kraus et al., 1993 a, see Sect. 8.3) and others. Diazirines, which are closely related to diazoalkanes (see Sect. 5.4), are also a source of carbenes. Various carbenes that were not available (or only with great difficulty) from other precursors have been investigated by Moss and coworkers in the second phase of their systematic elucidation of the selectivity of carbenes in cyclopropanation (see review: Moss, 1989). Detailed studies of kinetics and products of diazirine photolyses demonstrate that the mechanism of azo-extrusion is very similar to that of the dediazoniation of diazoalkanes. As diazirines are not within the scope of this book, we mention here only one investigation of a diazirine azo-extrusion, because the carbene formed (identified as singlet) reacts with N2 and the corresponding diazoalkane is detected in small yield (8-9; O'Gara and Dailey, 1992)*. N2 tl

hv,340nm

Br

+

CF3

N2 ^

IT

Br

CF3

V

;

Ketone 4-toluenesulfonylhydrazone salts can be used for carbene formation. The mild thermolysis and the photolysis of these salts leading to diazoalkanes are known as the Bamford-Stevens reaction. If run under more energetic conditions, the metastable diazoalkanes form carbenes and their subsequent products (e.g., alkenes), or, in the presence of mild acids, products of carbocations (see Subsect. 2.5.2). Basically, there are three types of process by which diazoalkanes dissociate into dinitrogen and a carbene, namely thermolysis, photolysis, and catalysis with a transition metal or a metal complex. Pure carbenes are likely to be formed only by thermolysis or photolysis in the gas phase. In solution, these two processes probably lead under all conditions, even in the presence of practically inert solvents, to (at least loose) addition products with solvent molecules. Metal catalysis in the decomposition of diazoalkanes has been known for almost a century (Silberrad and Roy, 1906), but it was only in 1952, i.e., shortly after carbene chemistry had started (see Sect. 8.1) that Yates realized that transition metal catalysts generate transient electrophilic metal carbenes (8.8, Scheme 8-10). As these complexes are not carbenes in the proper sense, but react in most cases like carbenes, * Structural and energetic comparisons between diazoalkanes and the corresponding diazirines are discussed in Sect. 5.4.

316

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates [MLn]+

R2C = N2 ' -N2 ^'

[y\/i=CR2 *

(8-10)

^ U\/i-cR2] 8.8

Closs and Moss (1964) suggested to call them "carbenoid reagents" or, simply, "carbenoids". In the last three decades, interest in the synthetic uses of carbenes shifted first from thermolysis to photolysis and now strongly to carbenoids. Most fundamental principles of carbene reactions are based, however, on thermolytic and photolytic investigations. As emphasized by Hoffmann and coworkers at an early date (Gleiter et al., 1972), the thermal dediazoniation of diazoalkanes is not a linear fragmentation, by a lengthening of the C = N double bond in the C---N---N axis, as one might assume in analogy to the dediazoniation of an aromatic diazonium ion. Such a process is symmetry-forbidden, as the carbene formed would be in an excited singlet state (Py) and not in the singlet ground state (Fig.8-2) *. It is, therefore, likely that fragmentation does not follow this pathway: in the case of diazomethane, the N2 molecule being formed turns out of the C — N — N axis during dissociation, as one would expect on the basis of the Woodward-Hoffmann rules (Woodward and Hoffmann, 1969). This turn possibly also explains — at least qualitatively —the equilibration between diazomethane and diazirine (see Sect. 5.4)**.

Fig. 8-2. Symmetry-forbidden dediazoniation of diazomethane (after Gleiter et al., 1972).

Yamabe et al. (1980) investigated this problem in more detail and confirmed the assumption that the thermal and photolytic dediazoniation along the path of least motion (a C2v dissociation) is unfavorable. Nevertheless, it is possible if the symmetry of the system is reduced to C2 or Cs. Closed-shell Hartree-Fock MO calculations led to the result that the lowest excited state of diazomethane can initiate the dediazoniation through the bent-in-plane path (C5). These results were corroborated by Csizmadia's group (Wang et al., 1991) in ab initio calculations with 3-21G and * The excited singlet (pj) is not shown in Fig. 8-1 (Sect. 8.1). ** The formation of diazirine from diazomethane may, however, also proceed via complete dissociation to CH2 and N2. So far as we are aware, this question has not been verified experimentally.

8.2 Formation of Carbenes and Carbenoids by Dediazoniation of Diazoalkanes

317

6-31G* basis sets and geometry optimizations by fourth-order M011er-Plesset calculations. Analogously, the dediazoniation of 2-diazoacetaldehyde was studied. We discussed further theoretical investigations on carbene formation in Section 5.4 in the context of comparisons of diazomethane with diazirine (e.g., Yamamoto et al., 1994). In these theoretical investigations, the product was always the singlet carbene. As discussed in Section 8.1, however, the energy gap between singlet and triplet is in most cases very small and, in general, in favor of the triplet. This idea was proposed by Bethell et al. at a relatively early date (1965, 1970, 1971, 1974), partly based on early observations of product formation of carbenes - a subject that we will discuss in Section 8.5. Quantitative results on the kinetics of these equilibria became available only with the advent of laser flash photolysis*. The latter was used by Schuster's group (Grasse et al., 1983) for the photolysis of diazofluorene in acetonitrile at room temperature. The reaction leads to the formation of the singlet carbene (fluorenylidene), which undergoes intersystem crossing to the triplet with a rate constant of 3.6 x 109 s"1. A few years later, Turro et al. (1987a) were able to determine the corresponding rate constant for the parent carbene (methylene) in solution at 0°C: k = 8 x 108 s"1. As expected, these rates are close to diffusion control, but significantly slower than in the gas phase (Langford et al., 1983). Simon and Peter (1984), and Griller et al. (1984) have reviewed laser flash photolysis of carbene formations. Absolute rates of singlet-triplet interconversions A:ST and &TS have been summarized for carbenes by Eisenthal et al. (1985) and by Schuster (1986). There are a series of photochemical investigations in which product ratios indicate that, in some cases, it is neither the singlet nor the triplet carbene in their ground states that forms certain products with a given substrate. The results indicate that photoexcited diazo compounds or carbenes in excited states may react. Evidence for such mechanisms came hitherto only from product studies, some of these cases will be mentioned only in the sections on the corresponding products. Potential reactive intermediates in carbene formation are summarized in Scheme 8-11. The latter includes the excited singlet and triplet carbenes, as well as the formation of triplets by triplet sensitizers such as benzophenone or thioxanthone (3Sens) and the direct formation of products from the excited diazo compound with the substrate S: . Product

R2ctr (8-11)

3

Sens

* Conventional flash photolysis was first used in 1976 by Closs and Rabinow for the determination of a rate constant in a carbene reaction.

318

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

formation of the various forms of carbenes are not included in this scheme, but such processes will be discussed in succeeding sections. As mentioned earlier in this and the preceding section, carbene reactions starting with diazo compounds can be catalyzed by transition metal complexes that contain an open coordination site on the metal. The metal atom is therefore electrophilic and adds to the nucleophilic C (a)-atom of the diazoalkane, followed by dediazoniation (8-10, earlier in this section). The metal carbene formed (8.8; LnM = CR2 in 8-10) transfers the carbene to a substrate S: and the original metal complex [MLJ is regenerated (except the weakly bound ligand B), as shown in the catalytic cycle of Scheme 8-12 (Doyle, 1986 a, 1986 b). The overall reaction bypasses the carbene proper and, therefore, the reagent 8.8 is called a carbenoid. The metal-carbene complex 8.8 may be called a carbene precursor in analogy to precursors in photolytic carbene formation from diazo compounds. SCR2

R2C =

8.3 Addition of Carbenes to Alkenes In this and the following sections, we shall discuss the reactions of carbenes only on the basis of some typical examples. A comprehensive treatment would be the subject of a monograph devoted to carbenes only. The addition to alkenes is the most important reaction of carbenes; first, because it is the simplest synthesis of cyclopropanes (particularly if carbenoids are used, see Sect. 8.7), and, second, it has been very well studied mechanistically. At a very early period of modern carbene chemistry, SkelPs group (Skell and Woodworth, 1956; Skell and Garner, 1956; Woodworth and Skell, 1959; Skell, 1985) found what became known as the Skell-Woodworth rule. Singlet and triplet carbenes can be differentiated by studying the products obtained in the cycloaddition of carbenes to alkenes: singlets only yield the corresponding stereospecific products with (Z)- and (jE')-substituted ethenes, but the addition of a triplet carbene results in non-specific mixtures with both (Z)- and (^-substituted alkenes. These results can be easily rationalized, as the bond-forming electrons of the singlet and triplet are paired and unpaired, respectively. On the assumption that in case of the singlet the

8.3 Addition of Carbenes to Alkenes

319

p-7t and sp2-7i* orbital overlaps with the alkene take place synchronously, or one rapidly succeeds the other, an (jE')-alkene will form a taws-cyclopropane (Scheme 8-13). In the case of the corresponding reaction with a triplet carbene, however, the two unpaired electrons cannot form a new covalent bond, as they have parallel spins. Thus, one of the unpaired electrons will form a bond with that 7i-electron of the alkene that has the opposite spin. This process leaves two unpaired electrons with the same spin, which can form a bond only after one of them has reversed its spin in a collision process. For a certain time, the biradical allows fast rotation about the CC bond of the original alkene. Thus, a mixture of cis- and £rafls-cyclopropane derivatives will result as final product (Scheme 8-14).

H

\

c=c

R

/R

+H2c

H

H

\ /R C=C R H

(8-14)

Experimentally, Doering and LaFlamme (1956) found, in the direct photolysis of diazomethane in (Z)-but-2-ene, a ratio of 46:1 of the cis- and taws--l,2-dimethylpropanes. Nevertheless, a ratio of only 19:1 was obtained in the photolysis sensitized by benzophenone, whereby the singlet is transformed into the triplet (Kopecky et al., 1962). As the singlet is usually the primary product of the dediazoniation and, as it has, in most cases, a higher energy than the triplet (see Sect. 8.1), the carbenes react generally as the singlet before they have a chance to decay into the triplet state. As the rate of that decay is very high (k = 108-109 s"1, see Sect. 8.2), the rate of the singlet addition to the alkene is even higher, i. e., at or very close to diffusion control. This conclusion was made and evaluated before direct determinations of these rate

320

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

constants of carbenes with alkenes became measurable thanks to laser pulse photolysis: the groups of Turro and Moss measured the rate constants of addition of fluoro-, chloro- and bromophenylcarbene to four alkenes (Turro et al., 1982, 1987b; Gould et al., 1985). In their comprehensive investigation of chemical and physical properties of fluorenylidene (8.10, Scheme 8-16), Schuster and coworkers (Grasse et al., 1983) determined the rate constants of this carbene with 15 alkenes and alkadienes. Fluorenylidene is a particularly interesting carbene because of its rapid interconversion between singlet and triplet, and the very small energy gap between these states (<4.5 kJ mol"1). The increased energy and reactivity of triplet fluorenylidene may be traced back to the enforced contraction of the carbene bond angle to 108°, relative to 136° in triplet CH2 (see Sect. 8.1), an effect that is not present in diphenylcarbene. The photolysis kinetics and the singlet-triplet gap of diphenylcarbene (23 kJ mol"1) were investigated earlier by Closs and Rabinov (1976) and by Eisenthal, Turro and coworkers (1980). Due to the small energy between singlet and triplet, reactions of triplet fluorenylidene were claimed to be found already by Jones and Rettig (1965). Grasse et al. (1983), however, are careful in their conclusions, as indicated in Scheme 8-15, by the quotation marks. It is taken from their paper. 1. Hydrogen abstraction 2. Nonstereospecific cyclopropanation "triplet-reactions ('8.10

«~^

3

8.10)^^ 8.9 - N2

(8-15)

"singlet-reaction 1. Ether formation 2. Ylide generation 3. Stereospecific cyclopropanation

(8-16)

8.10

The other carbene reactions shown in Scheme 8-15 will be discussed in Section 8.5. There again, we will see that violations of the Skell-Woodworth rule can be explained if the size of the singlet-triplet gap and the rates of forward and reverse intersystem crossing of carbenes are taken into account. In addition, it should be

8.3 Addition of Carbenes to Alkenes

321

mentioned that excited cyclopropanes, if formed as primary products, e. g., at low pressure in the gas phase, may undergo cis/trans-isomerization after they have been formed (see Rabinovitch et al, 1959; Frey, 1959). In the 1980's, it became possible to directly measure rates of thermal carbene reactions with alkenes in the gas phase. In two papers of Wagner's group (Bohland et al., 1986; Kraus et al., 1993a), the reaction rates of triplet methylene with an excess of four alkenes, namely ethene, 2,3-dimethylbut-2-ene (tetramethylethene), cyclohepta-l,3,5-triene, and hexa-l,3-diene, were measured in helium gas phase at a temperature of 23-455°C. Methylene was formed from ketene and the increase in product concentration was determined as a direct measure of CH2 in a far-IR laser magnetic resonance spectrometer (built for this purpose) with discharge flow and flash photolysis systems (Bohland et al., 1984). The primary product of ketene is the singlet CH2, which forms the triplet by collisional deactivation with a secondorder rate constant that is 103-104 times higher (Langford et al., 1983) than those of the reactions of the triplet with the alkenes mentioned. Measured rate constants were, however, corrected for the small contribution from the singlet reaction with the alkene. The evaluation of the rate constants with all four substrates (range 105-108 M"1 s"1) by the Arrhenius equation resulted in pre-exponential factors that are almost the same for all four reactions (3.2-8.6 x 109 M"1 s"1) and very small activation energies (Ea = 14.4-24.1 kJ mol"1). In another investigation, Wagner's group (Bohland et al., 1985) also determined the rate constant for 1 CH2 + CH2 = CH2. It was found to be 7.9 x 1010 M"1 s"1, and the experiments clearly indicated that this rate is temperature-independent *. The rate constant corresponds roughly to the rate constant of the triplet at 300 °C, but the triplet reacts about 100 times slower than the singlet at room temperature. The main primary product of the thermolysis with ethene was cyclopropane, provided that the alkenes were present in large excess. The observed isomerization to propene was shown to be a consecutive reaction. Cvetanovic et al. (1967) also found products that indicate the formation of allyl radical intermediates leading, in multistep reactions, to hexa-l,3-diene, pent-1-ene, and butane. The authors assumed that these compounds resulted from recombination of allyl and ethyl radicals. It is well known from combustion chemistry that the addition of methylene precursors to unsaturated hydrocarbons leads to higher hydrocarbons as precursors of soot (see e.g., Homann and Wellmann, 1983). On the other hand, it is unlikely that methylene is formed from methane or other hydrocarbons in the pyrolysis of coke. In contrast to methylene, its analog silylene is a product of the pyrolysis of silane and disilane (8-17; Purnell and Walsh, 1966; Bowrey and Purnell, 1970). Laser-induced fluorescence was used to study the formation of silylene and its reactivity (see, e.g., Baggott et al., 1988; Jasinski and Chu, 1988), but silylene is not within the scope of this book as there are no diazo compounds involved in its chemistry. Literature in which the reactivity of silylene is compared with that of methylene is reviewed briefly in a publication of Skancke (1993, p. 640). * Theoretical work (Zurawski and Kutzelnigg, 1978) also suggests that there is no activation barrier, i. e., no temperature dependence of the rate.

322 Si2H6

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates ^

SiH2

+ SiH4 (8-17) SiH2 + H2

We mentioned above that Bohland et al. (1985) found that the rate of the gasphase reaction of singlet methylene and ethene was temperature-independent. This result corresponds to the activation energy of halophenylcarbene reactions with alkenes in solution by Turro et al. (1982), e.g., Ea « 4 kJ mol"1 for the addition of C6H5CC1 to hex-1-ene. Even negative activation energies were obtained for addition to 2-methylbut-2-ene and 2,3-dimethylbut-2-ene. Differential activation parameters for addition of C6H5CC1 to (H3C)2C = C(CH3)2, (H3C)2C = CHCH3, (£>CH3CH = CHC2H5, and to H2C = CH-C4H9 yielded AA/7* values ranging from -18 to -6.3 kJ mol"1 in that sequence of the four alkenes, AAG* in the range 9.2-18 kJ mol"1 and an almost constant entropy term AA/S* ( — 23 to -20Jmol~ 1 K"1). The differences in AA/f* and AAG* correspond to the classical alkene reactivity sequence (Skell and Cholod, 1969). Negative activation energies may be due to a reversible and thermodynamically unfavorable formation of an alkene-carbene complex. Moss (1989) does not consider that reason as likely, because complexes have never been observed, nor is their existence supported by reasonably high level calculations (Houk et al., 1984, 1985). Houk concluded that A//* decreased continuously along the reaction coordinate (i. e., A/7* and Ea were negative), but that there was a free-energy barrier to addition (AG* > 0) because of a dominant unfavorable entropy of activation. Model potentials for the description of A//* and TAS* allow a satisfactory description of the experimental data. We think that this mechanism is still open for further discussion. The laser-flash investigations involving spectra of transient intermediates (e.g., Grasse et al., 1983) clearly demonstrate the experimental difficulty in the detection of an additional species. Therefore, the fact that no alkene-carbene complex was observed is not safe evidence against such a hypothesis (but, of course, neither for its existence!). It is remarkable that a relatively early empirical approach to the reactivity problem of carbenes in cyclopropanation is still useful after absolute rate constants for carbene formation and for their reaction with alkenes became available and highlevel calculations on these processes became feasible. This approach is Moss' carbene selectivity index, W C XY> developed in the 1970's (Moss and Mamautov, 1970; Moss et al., 1977; reviews: Moss, 1980, 1989), i.e., at a time when absolute rate constants for carbene reactions were not yet available. Therefore, Moss and coworkers determined product ratios (ki/kQ) of CXY(£j) and CC12(£0) as standard carbene with 2-methylprop-l-ene as reference alkene and a standard set of four other alkenes: (H3C)2C = C(CH3)2, (H3C)2C = CHCH3, (Z)- and (£)-CH3CH = The term mCXY is defined as the least-squares slope of vs. log(Ar1/^o)cci2' Originally, ten carbenes were evaluated by the selectivity index, covering a range of mcxv = 0.29-1.48 (CC12 = 1.00). The term mcxy correlated fairly well with equation (8-18), where £X,Y represents the sums of Taft's appropriate dual substituent parameters (see Ehrenson et al., 1973).

8.3 Addition of Carbenes to Alkenes mCXY = -1-10^ x y O R + + 0.53^XY°F - 0.31

323 (8-18)

Besides the common properties of parameters like mcxy (correlation of selectivities of known and unknown carbenes), equation (8-18) indicates that increasing 7i-electron donation and increasing inductive withdrawal by X and Y both augment the selectivity of the carbene CXY. As selectivity is inversely related to reactivity, Zollinger (1990) used the inverse coefficients of (8-18), i.e., £ R =1.10 and £F = —0.53, for a mechanistic interpretation of reactions with opposite signs of resonance and field reaction constants*. This result can be understood on the basis of HOMO-LUMO interactions in these cyclopropanations (Moss et al., 1979; Rondau et al., 1980; for an earlier hypothesis see Hoffmann, 1968). As shown in Figure 8-3, the carbene is inherently both an electrophile and a nucleophile. Depending on the character of substituents, it is, in the transition state, the [LUMOcarbeng-HOMOaikeneKP/71) electrophilic (E) orbital interaction or the [HOMOcarbene-LUMOalkene](o/7i*) nucleophilic (N) interaction that is dominant**.

E

P/TI Fig. 8-3. HOMO-LUMO interactions in carbene-alkene cycloadditions (after Moss, 1989).

This FMO approach easily allowed an extension of the group of ten carbenes used for the original work with the selectivity index mcxy to other, less electrophilic carbenes that became available in the 1980's by various methods (see review: Moss, 1989): Electrophilic carbenes, such as CC12 and CF2, add with increasing rate to increasingly electron-rich olefins ([LUMO?arbene-HOMOalkene] dominating), whereas nucleophilic carbenes such as (H3CO)2C add with increasing rate to alkenes of decreasing rc-electron availability. The opposite signs in (8-18) explain that the racxy * Reactions with opposite signs of resonance and field reaction constants are rare. In our compilation, only 14 such reactions are mentioned (Zollinger, 1990, Table I), among them 6 involving dediazoniations (see Zollinger, 1994, Sect. 8.4). The main question is still open: What is the basic reason that there are thousands of reactions for which the classical Hammett equation (i. e., field and resonance effects operate in the same direction) is applicable but only few processes in which the field and resonance effects have opposite signs. ** One realizes that this frontier molecular orbital (FMO) approach for this [1 + 2]cycloaddition is analogous to that for 1,3-dipolar cycloadditions (Sect. 6.3).

324

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

curve has maxima at both ends, corresponding to strongly electrophilic and strongly nucleophilic carbenes. Inbetween are the so-called ambiphilic carbenes, e.g., H3COCC1 (Moss et al., 1977; see also Moss et al., 1987). Before we close the discussion of carbene reactions with alkenes we mention tetrahedral boron hydride-substituted diazomethanes (8.11-8.13) which were obtained by the group of Jones (Li and Jones, 1992; Li et al., 1993) by manipulating substituted o-carboranes, as shown in (8-19). Reaction of 8.13 with (J£')-but-2-ene yielded the pure (^-derivative, i.e., the product of singlet addition. With (Z)but-2-ene 3 % triplet reaction product was observed. The percentage of triplet products was higher with 8.13 (22 and 18% with (E)- and (Z)-but-2-ene, respectively) (Huang et al., 1992).

(8-19)

•

•

: location of carbon atoms

8.11 8/|2

8.13

R = H, H R

R = CH3,CH3

Formation and reactions of alkylidenecarbenes (R2C = C:) were already mentioned in Section 2.9. The work of Gilbert and Giamalva (1992, see also preceding papers from Gilbert's group in reference 7) demonstrates that in the cyclopropanation of 2-methylprop-l-enylidene ((CH3)2C = C:) with substituted styrenes it is the singlet that reacts at — 78 °C in tetrahydrofuran in the presence of potassium tertbutoxide. A Hammett GQ evaluation gives good evidence for the electrophilic character of the carbene (Q = —0.64). The ^-values for 2-methylprop-l-enylidene cover in various solvents and with several carbene precursors a large range (— 0.44 to —4.3). 4,5-Dihydro-l//-pyrazoles can be excluded as intermediates because their formation is normally characterized by positive ^-values (Murahashi et al., 1982).

8.4 Addition of Carbenes and Carbene Precursors to Aromatic Hydrocarbons and to Fullerene[60] In Section 8.1 it was briefly discussed that carbenes react with benzene leading to various products (8-3). With photolytically generated methylene, toluene and cycloheptatriene are obtained in the ratio 1: 3.5 (Doering et al., 1953; products with

8.4 Addition of Carbenes and Carbene Precursors

325

diazoacetate: Doering et al., 1956b) to 1:4.1 (Hartz et al., 1993). This ratio is dependent on the solvent and highest in the gas phase (1: 3.3; see discussion by Schoeller, 1975). The formation of toluene is a CH insertion reaction, that of cycloheptatriene is likely to proceed via norcaradiene (see 8-3), because more electrophilic carbenes such as dicyano- and bis(trifluoromethyl)carbene yield the norcaradiene derivatives, which rearrange into the corresponding cycloheptatrienes (Ciganek, 1965 b, 1967, 1968) either photolytically or thermally. With the slightly less electrophilic carbene generated from diazoacetates the norcaradiene was not observed in reaction with benzene, but only with more nucleophilic substrates, e.g., furan and thiophene (Schenck and Steinmetz, 1963). In additions of ethyl diazoacetate to naphthalene, mono- and dicyclopropanation were observed (8-20, Huisgen and Juppe, 1961), with methylene the dominant product was 2-methylnaphthalene (Hartz et al., 1993). The same authors found that, in the reaction of methylene with toluene, the products are methylcycloheptatrienes (ca. 77%, isomers not separated), ethylbenzene (10%), and the three dimethylbenzenes (13%). H

N2CH—CO2R

140 150 c

~

°>

\,C0 2 R

^^^^J^ 52%

(8-20)

10%

4%

In recent years, the groups of Nefedov and Olah investigated the methenylation of aromatic hydrocarbons in solution and Wagner in the gas phase (see below). The transition metal-catalyzed reactions will be discussed in Section 8.7. Olah's group (Hartz et al., 1993) investigated the reaction of singlet and triplet methylene with benzene, toluene, hexamethylbenzene, pentafluorobenzene, naphthalene, and anthracene. Singlet methylene was generated by photolysis of diazomethane (no details given). For triplet methylene, diazomethane was irradiated (313 nm) in the presence of benzophenone as sensitizer. Kinetic isotope effects were determined by using equimolar solutions of deuterated and undeuterated substrates. The results, however, are not very conclusive; in our opinion, there is only relatively clear evidence that a common intermediate for the two products from benzene formed with the singlet can be excluded, because the two isotope effects found for

326

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

toluene (kn/kD = 1.34 ± 0.04) and for cycloheptatriene (1.05 ± 0.04) are clearly different. With triplet methylene, they are for toluene 12.1 ±1.0 and for cycloheptatriene 1.06 ± 0.04. A series of ab initio calculations at MP2/6-31GV/RHF/6-31G* and UMP2/6-31GV/UHF/6-31G* levels of theory were carried out to investigate benzynium-methylide structure 8.14 and the biradical structure 8.15 as potential intermediates. Species 8.14 may be a transition state in the valence isomerization of norcaradiene into cycloheptatriene, 8.15 may be an intermediate on the way to norcaradiene. H

8.14

CH2

8.15

In conclusion, more detailed experimental and theoretical work would be welcome for this reaction system in solution. Wagner's group (Hack et al., 1988; Kraus et al., 1993 b) investigated the kinetics in the gas phase of the reaction of singlet and triplet methylene with benzene, naphthalene, phenanthrene, anthracene, and biphenyl at 172-417 °C (for benzene 23-410°C) using the isothermal discharge flow system with far-IR laser magnetic resonance detection, already mentioned in Section 8.3. It was possible to separate two competing primary processes, i. e., the reaction of the triplet with the aromatic hydrocarbons vs. the collisional excitation of the triplet to the singlet state (followed by reaction of the singlet with the aromatics), under the reasonable assumption that the activation energy of the triplet reaction with the bi- and tricyclic aromatic hydrocarbons is smaller than the singlet-triplet energy gap (see also Kraus et al., 1993 a). On this basis, rate constants for the reactions of the singlet at room temperature with these aromatic hydrocarbons were estimated to be so fast that every collision of 1CH2 and, e.g., C6H6 leads to reaction. These data allowed calculation of the rate constants for the corresponding reactions of the triplet for the temperature range mentioned. The first step is considered to be the formation of an addition complex of 3CH2 to the aromatic Ti-system and, from there, to a vibrationally excited triplet diradical as a first intermediate. The formation of stable products was rationalized on the basis of unimolecular rate theory (Bohland et al., 1989). This theory suggests a relatively unstable norcaradiene, which rearranges rapidly into cycloheptatriene, but not into toluene. The latter result is in contradiction to experiment. Conclusions for the higher aromatics are only tentative. Unfortunately, experimental product determinations were not carried out. A logical continuation after the reactions of carbenes with aromatic hydrocarbons would be the corresponding reactions with aromatic annulenes, i.e., [10]-, [14]-, [18]annulene, etc. No work has been published on that subject, mainly due to the inaccesibility of the simple [4n + 2]annulenes (n = 2,3,4; Vogel, 1994).

8.4 Addition of Carbenes and Carbene Precursors

327

An interesting aspect in the context of this section, however, is the question whether a carbene can add to the C (9) = C (10) bond of naphthalene and if in the product atoms C(9) and C(10) are connected to each other by a single bond in a cyclopropane derivative ('bisnorcaradiene') (8.16), or whether there is no longer a bond between them, i.e., l,6-methano[10]annulene (8.17; bicyclo[4.4.1]undeca-l,3,5,7,9-pentaene) is formed, or if an equilibrium between these two valence isomers can be detected.

8.16

8.17*

This problem was solved by VogePs group, but not directly with naphthalene as substrate. As discussed earlier in this section, naphthalene undergoes addition of carbenes in the 1,2-position only. Vogel et al. (1963) started with 1,4,5,8-tetrahydronaphthalene (8.18), which reacts with dichlorocarbene (from CHC13 and potassium tert-butylate) with high selectivity at the central double bond (8.19, Scheme 8-21). Bisdechlorination with sodium in liquid ammonia yields 8.20, which gives l,6-methano[10]annulene (8.17) after tetrabromination and treatment with alcoholic KOH (Vogel and Roth, 1964) or, more elegantly, directly with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) (Vogel et al., 1988). The UV and *H NMR spectra, in particular the A2B2 system of 8 protons at 8 6.8-7.5 and a sharp signal (2 protons) at 8 0.5 indicate a strong ring current and a strong shielding of the methano protons. These results are consistent with the annulene structure 8.17, but not with the cyclopropane derivative 8.16. This result was, at the time, very important for the theory of aromaticity, because the ring of the [10]annulene does not display the expected characteristics of aromatic compounds. The cause is steric hindrance between the H-atoms at C(l) and C(6), which does not allow a planar 10-membered ring. Substitution by the methano bridge, however, does allow planarization. Analogous methods were used by Vogel for mono- and bismethano[14]annulenes and for the interesting bridged 1,6:8,13-propandiylidene[14]annulene 8.21 (see Vogel et al., 1970a, 1970b and literature mentioned there).

8.18

8.19

8.20

8.17 (8-21)

* The heavy bonds indicate the aromatic (4n + 2) system of jr-electrons.

328

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

8.21

l,6-Methano[10]annulene (8.17) reacts with diazomethane by ring expansion to give bicyclo[5.4.1]dodecapentaene (8.22, and probably its double bond isomers). With triphenylmethyl fluoroborate as hydride-transfer reagent, bicyclo[5.4.1]dodecapentaenylium tetrafluoroborate (8.23) can be obtained, i.e., an aromatic carbocationic salt with 10n electrons (8-22). This reaction was also found by VogePs group (Grimme et al., 1965). The first step corresponds to the analogous reaction of benzene and demonstrates, therefore, the aromatic character of l,6-methano[10]annulene *.

8.17

BF4~

(8-22)

(

\^ 8.22

8.23

In 30 years since the synthesis and characterization of l,6-methano[10]annulene, Vogel and his coworkers made a very large number of other bridged annulenes available, either by replacing the methano bridge with other groups, e. g., by - O or — NH —, by the synthesis of the corresponding bis-, tris- and tetrakismethano[14]-,-[18]- and -[22]annulenes (e.g., 8.24), by synthesizing methano-bridged heteroaromatic annulenes (reviews: Vogel, 1980, 1982) and by linking the properties of l,6-imino[10]annulenes (8.25) via diimino[14]annulene (8.26) to the chemistry of porphyrine (8.27) and its homologs (review: Vogel, 1993).

CH2

CH2

CH2

CH2

8.25 ^x^

8.27

* For another reaction of 8.17, see Vogel et al. (1974).

8.4 Addition of Carbenes and Carbene Precursors

329

Exactly 29 years after VogePs ring discovery and structural elucidation of l,6-methano[10]annulene, his work became an important guide-line for a completely different type of methano-bridged species, namely for the structure of compounds obtained by reaction of diazoalkane-based carbenes with buckminsterfullerene[60] *, specifically for the work of Diederich (Isaacs and Diederich, 1993; Isaacs et al., 1993). It is really a fascinating experience for me as the author of this book to have seen the development from the start of carbene chemistry in 1950 (the investigation of Doering and Knox on the reaction with benzene) up to the more rewarding investigations with alkenes (Sect. 8.3), and simultaneously VogePs work on bridged annulenes (formally not at all related to diazo chemistry) and in 1993 that unexpected cross-fertilization found with methanofullerenes. We shall discuss first the beginning of diazo chemistry with fullerenes and subsequently the relation to methanoannulenes. Since the discovery of fullerene[60], the first representative of the family of spheroidal carbon molecules, by Kroto et al. (1985) and, in particular, after it had become available in larger quantities (Kratschmer et al., 1990), chemists developed interest in its functionalization (reviews: McLafferty, 1992; Pagan et al., 1992; Olah et al., 1993; Billups and Ciufolini, 1993; Kroto et al., 1994; Hirsch, 1994; Diederich et al., 1994b). Among these investigations were reactions with diazoalkanes published by WudPs group (Suzuki et al., 1991, 1992a; Wudl, 1992) and that of Diederich (Isaacs et al., 1993; Isaacs and Diederich, 1993). Wudl and his coworkers report that the reactions of C60 with diazomethane, its mono- and diphenyl derivatives, and with diazoacetate, all in toluene at room temperature proceed via a 1,3-dipolar cycloaddition to give the corresponding dihydropyrazoles and (by azo-extrusion) the bridged fullerenes. Analogously, two equivalents of buckminsterfullerene react with bis(diazoalkanes) (Suzuki et al., 1992a). In contrast to the first four publications of Wudl and coworkers, which do not contain the usual experimental details of the reactions, the first paper of Diederich's group (Isaacs et al., 1993) gives full information on the reaction of C60 with ethyl and tert-butyl diazoacetate in refluxing toluene (7 h). Equimolar amounts of ethyl diazoacetate and C60 gave, after chromatography on silica gel, a purple product fraction, which was shown by the detailed *H and 13C NMR analysis to be a mixture of the three (ethoxycarbonyl)methylene-bridged C60 isomers 8.28-8.30 in a ratio of ca. 1:1:3 under kinetic control. No evidence for isolable dihydropyrazole intermediates was found (no N in elementary analysis, no NN bonds in IR, no NMR signals attributable to dihydropyrazoles). The very different chemical shifts of the methylene and ethyl protons in the three isomers indicate that these protons are in clearly different environments. When the isomer mixture was heated in toluene for an additional 24 h, the color of the solution changed from purple (Amax = 597, 539, 425, 406, and 337 nm) to pink-red (Amax = 495, 429, 417, 404, 395, and 331 nm). The isolated product gave a less complex 1H NMR spectrum that corresponds to 8.28, which is obviously the equilibrated, most stable isomer of the three primary products. Analogous results were obtained in the reaction with tert-butyl * We call this compound here fullerene[60] or simply C60.

330

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates 5 = 6.79 ppm 5 = 4.31 ppm

ROOC

H

5

= 3 32

'

ppm

COOR

8.28

8.29

8.30

R = C2H5 or (CH3)3C (8 values for the ethyl ester)

diazoacetate (R = C(CH3)3), but with 8.29 as the thermodynamically most stable isomer. We will discuss these three structures later in this section. As mentioned briefly in Section 6.5, it should be emphasized that there is no clear evidence available whether cyclopropanes, including these methanofullerenes, are formed via dihydropyrazoles, i.e., by a 1,3-dipolar cycloaddition, or by the primary dediazoniation of the diazoalkane to a carbene that subsequently reacts with C60. It may be that the mechanism is a dipolar cycloaddition followed by azo-extrusion at low temperature (20°C, i.e., Suzuki's conditions), but a carbene reaction in boiling toluene (Isaacs and Diederich), as shown in Section 6.5, Scheme 6-37, pathways C and A, respectively. In addition, the dihydropyrazole may be the product of a sideequilibrium only, but the reagents form the cyclopropane-type methanofullerene via pathway C. A mechanism via primary dediazoniation is, however, unlikely as dediazoniation of diazoacetate without C60 in boiling toluene is much slower than it is in the presence of C60 (Diederich, 1994). Yet, the formation of methanofullerenes via carbenes was demonstrated unambigously by the use of carbenes from various other precursors than diazoalkanes. Nogami's group (Tsuda et al., 1993) showed that dichlorocarbene, generated by pyrolysis of sodium trichloroacetate in a mixture of benzene and 1,2-dimethoxyethane, reacts with C60 to give the [6,6]-closed methanofullerene, as shown by negative ion fast atom bombardment mass spectrometry (FAB MS) and by 13 C NMR spectroscopy. The preparation of (dimethoxymethano)fullerene (8.32) by Isaacs and Diederich (1993) was based on the use of the oxadiazole 8.31 as a convenient source for dimethoxycarbene, found by Warkentin's group (El-Saidi et al., 1992) (8-23). Methano-bridged C60 compounds can also be obtained from diazirine precursors, as shown by joint work of Vasella's and Diederich's groups (Vasella et al., 1992) and by Komatsu et al. (1993 a, 1993 b). Further possibilities for methanofullerene syntheses were found by Nakamura's group (Tokuyama et al., 1993) and by Rubin's group (An et al., 1994; Anderson et

8.4 Addition of Carbenes and Carbene Precursors

331

H3CO^ ^OCH3 ^>>

,OChh

/VA 8.31

T^A

(8-23)

^••^

8.32

al., 1994a, joint work with Diederich). Nakamura used cyclopropenone acetals to generate ethenyl carbenes (vinyl carbenes) by thermolysis and hydrolysis of the intermediate ketene acetals. Rubin used diethynyl carbenes obtained by thermolysis of lithium salts of 4-toluenesulfonyl hydrazones. Furthermore, substituted methanofullerenes can be produced by addition/elimination reactions (Bingel, 1993; Hirsch et al., 1994; Anderson et al., 1994a), but they are not within the scope of this book. Before we discuss experimental evidence for the structures of isomeric methanofullerenes, we return briefly to WudPs and Diederich's observations that isomer mixtures are formed with diazoacetates under kinetic control and that they equilibrate to 8.28 as most stable isomer. It is surprising, however, that, for the parent (unsubstituted) methanofullerenes C61H2, it was not possible to thermally rearrange isomers into the compound corresponding to 8.28. When Smith et al. (1993) synthesized C61H2 by photolysis of the corresponding dihydropyrazoles, they obtained a mixture (4:3) of two isomers and observed neither thermal nor photolytic interconversion. The electronic structure of C60 is best described as a fusion of [5]radialene and cyclohexa-l,3,5-triene substructures (Taylor, 1992; Hirsch, 1994). It is known that the double-bond character in the five-memberend rings in C60 is low. Methano bridging can take place, however, as we have already seen (8.28-8.30), at the [6,5] or the [6,6] ring junctions and, in addition, valence isomerization is possible in both cases. This results in four isomeric methanofullerenes and eight, if the two substituents at the methano C-atom are different. Structure and naming of the four isomers are shown in Figure 8-4. The most convincing evidence for structure 8.36, i.e., the [6,6]-closed isomer was provided recently by an X-ray investigation carried out jointly by Diederich's group at ETH Zurich and by Gross and coworkers at the Universite Louis Pasteur in Strasbourg. They found that the 61,61-bis[4-(trimethylsilyl)buta-l,3-diynyl]-l,2-dihydro-l,2-methanofullerene[60] (8.37) has bond lengths that are only compatible with a [6,6]-closed structure (Anderson et al., 1994b). At the same time, Osterodt et al. (1994) published the structure of another substituted methanofullerene[60], namely that of (3,4-dimethoxyphenyl)phenylmethanofullerene[60] (8.36, R and R = C6H5 and 3,4-(CH3O)2C6H3, respectively). A [6,6]-closed structure was also found for this compound.

332

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

8.33

8.34

[6,5]-open

[6,5]-closed

8.35

8.36

[6,6]-open

[6,6]-closed

Fig. 8-4. The four possible isomeric methanofullerenes (after Isaacs and Diederich, 1993).

(H3C)3Sk

/Si(CH3)3

8.37

8.4 Addition of Carbenes and Carbene Precursors

333

The paper of Diederich's group (Isaacs et al., 1993) includes a thorough analysis of the 13C NMR spectra of 8.28 (R = CH3CH2) and 8.29 (R = C(CH3)3) and of the primary mixtures of both reactions. All 32 fullerene resonances for the two pure isomers and the 96 resonances for the mixtures 8.28-8.30 with both diazoacetates could be identified. Assignments were in agreement with recent calculations of local ring currents in C60 by Pasquarello et al. (1992) and with the extensive and welldocumented work of Vogel in methano-bridged annulenes, as discussed above (8.16-8.17). 1H NMR spectra were published in a joint publication by Wudl's and two Italian groups (Prato et al., 1993a), providing experimental evidence for ring currents in methanofullerenes. Further work by Isaacs and Diederich (1993), combined with a literature review, showed that the results for compounds 8.28-8.30 can be generalized: Bridging in Qo by diazo compounds and by diazirines occurs both at the [6,6]- and the [6,5]ring junctions. These methanofullerenes can adopt a 7r-homoaromatic (open transannular bond) or a <7-homoaromatic structure (closed), as discussed above. So far, all methanofullerenes that are bridged at the [6,6]-ring junction have a closed transannular bond ([6,6]-closed, 8.36), but all derivatives that are bridged at the [6,5]-ring junction possess an open transannular bond ([6,5]-open, 8.33). Isaacs and Diederich (1993) explain this result convincingly by two effects: First, it is energetically more favorable to bridge the shorter [6,6]-ring junction in a (7-homoaromatic way, positioning the bridgehead C-atoms at shorter distance, and to bridge the longer [6,5]ring junction in a 7r-homoaromatic way, i. e., with a greater transannular distance. Second, and more important, in a [6,6]-closed methanofullerene, all double bonds are localized in cyclohexa-l,3,5-triene substructures, which corresponds to a favorable bonding arrangement in fullerenes. In contrast, mesomeric structures of the [6,6]-open valence isomer (8.35) show that three [6,5]-ring junctions have attained greater double-bond character, whereas two [6,6]-ring junctions show high single-bond character. Therefore, the [6,6]-open structure is energetically disfavored. In contrast to the valence-isomerization equilibria found for l,6-methano[10]annulenes (Vogel, 1982), however, the major driving force for the position of these equilibria in the four methanofullerenes is not substituent effects. The preference for [6,6]-closed fullerenes (like 8.28) relative to the [6,6]-open isomers and for the [6,5]open fullerenes (like 8.29 and 8.30) is best explained with the conservation of the favorable bonding in C60 with higher double-bond character at [6,6] bonds and higher single-bond character at [6,5] bonds. WudPs group, however, assumed open structures for [6,6]-ring-bridged (monophenylmethano)- and (diphenylmethano)fullerenes (Suzuki et al., 1991; Wudl, 1992), but later also closed structures (see Taylor and Walton, 1993, p. 688; Sijbesma et al., 1993; Prato et al., 1993b)*. The experimentally preferred formation of the [6,6]-closed and [6,5]-open isomers of methanofullerenes was corroborated by Diederich et al. (1994 a) in a PM3 com-

* I cannot help adding that this fact supports the remark I made earlier in this discussion of methanofullerenes: Wudl's preliminary communication do not supersede the results published in Diederich's two full papers.

334

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

putational study* and the investigations were extended to the theoretical and experimental evaluation of substituent effects at the methano bridge. The following substituted methanofullerenes were investigated: R = R = H, CH3O, COOC2H5, COO(f-C4H9), C6H5. For the parent compound (R = R=H), PM3 calculations predict that the [6,6]-closed isomer (8.36) and the [6,5]-open isomer (8.33) are almost equal in energy (1.4 kJ mol~ J in favor of 8.33). For all the substituted methanofullerenes, the [6,6]-closed isomer (8.36) is significantly more stable: R = R = CH3O : 19.6; COOC2H5:25.3; COO(f-C4H9): 26.2; C6H5: 30.6 kJ mol"1). It was possible to thermally rearrange the [6,5]-open isomer of the two malonate derivatives and the diphenyl substituted compound to the [6,6]-closed isomers, but not the parent compound. These results also demonstrate that the preservation of the bonding pattern within C60 is the dominant cause for the structure of methanofullerenes. The calculation of the geometrical parameters reveals a remarkable invariance in the geometries of the [1,5]- and [l,6]-methanoannulene sub-units within the fullerene spheres of all five compounds. The lack of variation with substituents strongly suggests that the valence isomer equilibrium is determined by the rigidity and electronic structure of the fullerene sphere itself. It is interesting to note that the [6,5]-open isomer (8.33) can avoid placing formal double bonds within five-membered rings, but only by violation of Bredt's rule, i. e., by placing double bonds at the bridgehead C-atoms. We mention briefly another reaction of C60, although it does not belong to additions of carbenes to fullerenes. It is, however, based on 2-diazoniobenzenecarboxylate as precursor for benzyne, which reacts with C60 as shown by Tsuda et al. (1992). A 1:1 product was isolated and analyzed, but no structure was proposed. Various methanofullerenes containing suitable substituents at C (61) undergo reactions to other products by means of those groups. Such processes are described in papers from the groups of Diederich and Wudl (see above and Wooley et al., 1993). These reactions are, however, outside the scope of this book, except the work on bis(phenethylamino succinate)C60, obtained from the corresponding 4,4'-disubstituted diphenyldiazomethane. Such compounds are claimed to inhibit an HIV-1 protease on the basis of the hypothesis that fullerene[60] has approximately the same diameter as the cylinder that describes the active site of that protease. These investigations were conducted by Wudl's group in collaboration with pharmaceutical chemists (Friedman et al., 1993; Sijbesma et al., 1993). A comprehensive review on syntheses, structures, and chemical properties of methanofullerenes has been published by Diederich et al. (1994b).

* PM3: See Stewart (1989). For some experience with other methods, see Diederich et al. (1994 a) and Raghavachari and Sosa (1993).

8.5 Insertion, Abstraction, and Rearrangement Reactions of Carbenes

335

8.5 Insertion, Abstraction, and Rearrangement Reactions of Carbenes We have already briefly discussed (Sect. 8.1) reactions other than cyclopropanation of alkenes that are typical for carbenes, namely insertion into C —H and O —H bonds, abstraction of H-atoms, and rearrangements. Except for ether formation (insertion into the OH bond) and rearrangement of diazocarbonyl compounds (Sect. 8.6) they are of little interest in organic synthesis. The relationship between the reactivities of singlet and triplet carbenes in some of these processes has, however, attracted the interest of many investigators. Chemical evidence from such studies led to the conclusion that the singlet state can be intercepted due to its higher energy and that it displays a different chemistry from that of the triplet, since Skell and Woodworth developed their rule in the late 1950's and indicated that it may also be applied to carbene reactions other than cyclopropanation. In Section 8.1 the observation of Doering et al. (1956a) was discussed, in which Doering demonstrated the extremely low (almost nonexistent) selectivity of methylene insertion in the photolysis of diazomethane in pentane. Is this a reaction of the singlet or triplet? An answer to this question was obviously impossible in 1956. More informative is a process described by Roth (1972). The direct and the sensitized (benzophenone) photolysis of diazomethane in toluene yields ethylbenzene, but a CIDNP effect can only be observed from the sensitized reaction. This result leads to the conclusion that the direct photolysis is a concerted CH insertion of a highly reactive species, whereas the sensitized reaction takes place by a hydrogen abstraction, followed by a radical addition (8-24). It is, therefore, likely that it is the singlet that reacts in the first reaction, but the triplet in the second process.

(8-24)

(C6H5)2CO

Moss and Joyce (1978) demonstrated in an elegant labeling experiment that the triplet abstracts an H-atom before the new CC bond is formed: Triplet fluorenylidene (3F1) abstracts an allylic H-atom at 77 K from 2-methylprop-l-ene, labeled with 13C at the CH2 group (8-25). In the radical pair 8.38 both termini of the allylic radical have an even chance (except for the 12C/13C isotope effect) to combine with the fluorenylidene triplet. A singlet insertion reaction would, however, bypass the radical pair and would not lead to scrambling of the label.

336

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

With the advent of laser flash photolysis techniques, it became possible to study the kinetics of the fluorenylidene triplet in low-temperature glasses where the equilibrium population of the low-lying singlet state is reduced (see work of Tomioka et al., 1980b, and earlier papers of Tomioka and reviews of Platz, 1988, 1990). Platz and coworkers (Ruzicka et al., 1992) measured the rate of decay of the fluorenylidene triplet and of the transient absorbance of the fluorenyl radical in methylcyclohexane-toluene and other matrices at 122-90 K. Hydrogen transfer from the matrix to the fluorenylidene triplet has a pseudo-first-order rate constant in the range 103-105 s"1. The corresponding Arrhenius plot is very interesting (Fig. 8-5). The clear break at ca. 101 K separates an activation energy of 23 kJ mol"1 from 5 kJ mol"1 above and below the break, respectively. The most likely explanation for that break is a change of dominant mechanism from 'classical' hydrogen abstraction (above 101 K) to quantum mechanical tunneling (for tunnel effects in general, see Bell, 1980, and for these reactions see Platz, 1988). The break was not observed in a perhalogenated (i. e., hydrogen-free) glass, but was found in 2-methyltetrahydrofuran. In ethanol the fluorenylidene singlet can be trapped at room temperature by insertion into the OH bond prior to intersystem crossing. The corresponding product, 9-ethoxyfluorene is even detectable in ethanol at 77 K. Theoretical studies on carbene insertions into XH bonds are based essentially on investigations by Schaefer's group (Bauschlicher et al., 1976, 1977) on the pathway for singlet methylene into the hydrogen molecule (X = H) to afford methane. Later, insertion of methylene into methane and ethane CH bonds have been calculated at the Hartree-Fock level (Gordon et al., 1987, and Gano et al., 1991, respectively). With third-order Moller-Plesset perturbation theory corrections, the barriers for insertions were found to be very small (<0.8 kJ mol"1), consistent with experimental data. Bach et al. (1993) developed an FMO model for insertion of various carbenes into CH bonds of methane and ethane. The transition states are classified as o or n approaches, in which the empty carbene p orbital is aligned either with the oCH2

8.5 Insertion, Abstraction, and Rearrangement Reactions of Carbenes

337

122 K 13 12 11 90 K

In/c 10 9 8

h-

J

85

90

I

95

100

105

110

4

1/T(x10 ) Fig. 8-5. Arrhenius plot of the pseudo-first-order decay of 3F1 in methylcyclohexane-toluene (Tin K), after Ruzicka et al. (1992).

or the TCCH2 fragment orbital. The a approach is slightly favored over the n approach for CH2, HCCH3, C(CH3)2, CHF, and CF2. Vinylidene (C = CH2), however, shows a slight preference for the n approach. It is interesting to note that the energy barriers of these insertions do not correlate with HOMO or LUMO energies or their energy gaps, but with the singlet-triplet energy differences of these carbenes. The authors also performed calculations of methylene insertions into O-H and C-F bonds. As mentioned in Section 8.1, carbenes easily undergo insertion into O —H bonds. At an early date, Kerr et al. (1967) found that in the photolysis of diazomethanetert-butanol mixtures insertion is eleven times faster at O — H than at C — H bonds. The relative rates of ether formation for methanol, ethanol, 2-propanol, and tertbutanol are 2.01:1.95 :1.37:1.00. Before that investigation, Kirmse (1963) postulated that diphenylcarbene is protonated to form the diphenylmethyl carbocation, which, as a strong electrophile, adds to the alcoholate anion (or to the alcohol followed by deprotonation) forming the ether (8-26a). Bethell et al. (1969, 1971), however, favored an electrophilic attack of diphenylcarbene at the O-atom, i. e., an ylide intermediate on the basis of isotope effects (8-26 b). Finally, a concerted process via the transition state 8.39 may be feasible (8-26 c). For various mono- and bicyclic carbenes, e. g., benzocycloheptenylidenes (Kirmse et al., 1981; Kirmse and Sluma, 1988; Kirmse et al., 1993a) and cyclopentenylidenes (Kirmse et al., 1985), product and label distribution were compatible with mechanism (a), but not with mechanism (b). The photolytic reactivity of diazomethane with the four aliphatic alcohols, mentioned above, is in contradiction to the gas-phase acidities of these alcohols: Gaseous tert-butanol is the strongest acid among them (see Blair et al., 1973; Arnett et al., 1974), but according to Kerr et al.'s

338

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

Ar2CH—OR

(8-26)

8.39

measurements (1967) ether formation was slower than with the other alcohols. Towards diphenylcarbene, however, the reactivity of alcohols in solution increased with increasing acidity (Eisenthal et al., 1985). Kirmse et al. (1990) generated five substituted diphenylcarbenes from the corresponding diazomethanes by laser flash photolysis in acetonitirile-water mixtures or in trifluoroethanol and were able to measure the rate constants and the visible spectra after the flash. The results obtained corresponded to rates and spectra of the respective diarylcarbocations observed in time-resolved measurements by heterolytic photocleavage of methylsubstituted diarylmethanes (Ar2CHX, X = OAc or Cl), a method developed by McClelland et al. (1988, 1989)* The kinetic isotope effect A:H/&D found by Moss et al. (1988) for attack of the significantly nucleophilic dimethoxycarbene on CH3OH(D) suggests a substantial OH to carbene proton transfer during this reaction. It seems, therefore, that — in spite of good evidence for the carbocation mechanism (8-26 a) — the situation is still ambiguous. This was also realized by the group of Moss (Du et al., 1990). They investigated the reactivity of dimethoxycarbene and fluoromethoxycarbene with methanol, ethanol, 2-chloroethanol, 2-fluoroethanol, 2,2,2-trifluoroethanol, l,l,l,3,3,3-hexafluoropropan-2-ol and acetic acid. The carbenes were generated photochemically from the appropriate diazirines. We will not discuss the experimental results, only the major tentative conclusion — expressed by the authors in a very cautious form! They proposed that "relatively unstable, predominantly electrophilic carbenes, such as C1CC6H5, probably react with the nucleophilic MeOH by a rate-determining ylide-type LUMO(p)/alcohol HOMO(O-2p) interaction", cf. 8.40, and "A highly stabilized nucleophilic carbene, such as (H3CO)2C, probably reacts predominantly by a proton transfer", i.e., a mechanism involving the transition state 8.41. In addition, the authors express the opinion that between these extremes the concerted mechanism via the transition state 8.39 may be considered (this process, not necessarily with diarylcarbenes, is shown in Scheme 8-26 c).

* Recently, such carbocation formations were studied kinetically by stopped-flow laser-flash photolysis by Scaiano's group (Belt et al., 1993). The quantum yield of diphenylcarbocation formation is low (0.007).

8.5 Insertion, Abstraction, and Rearrangement Reactions of Carbenes

339

These ideas fit very well to our discussion in Section 8.3, where we showed that carbenes may react predominantly via the HOMO or via the LUMO, or, in other words, that the opposite signs of the resonance and field effects of carbene substituents and of the substrate lead to correlations of reactivities that cannot be explained by a standard combination of resonance and field effects. One hopes that, some time in the future, there will be a sufficient number of strictly comparable rate coefficients of carbenes with alcohols to evaluate them with a dual substituent parameter system, as we have done for cyclopropanations with substituted carbenes (Zollinger, 1990). Since the pioneering study of Closs and Rabinow (1976), several authors showed that the reactions of carbenes with alcohols occur via the singlet and that the rates indicate diffusion control (Eisenthal et al., 1980; Grasse et al., 1983; Du et al., 1990). To the best of our knowledge, positive evidence for ether formation of triplet carbenes with alcohols can not be found from the literature. No triplet reaction was detected, even for 2,2',4,4/,6,6'-hexamethyldiphenylcarbene, which, for steric reasons, is a carbene with very clear separation of singlet and triplet reactions (Nazran and Griller, 1984). Kirmse (1994) has reviewed reactions of carbenes with O — H bonds. A general mechanistic problem exists with alkylcarbenes because they are often difficult to detect as metastable intermediates due to intramolecular insertion. In the case of l-(bicyclo[2.2.1]-heptyl)diazomethane (1-norbornyldiazomethane), Bian and Jones (1993) showed that the formation of the carbene can be demonstrated by the stereospecific addition to alkenes, leading to the corresponding cyclopropane derivatives. The stereospecificity is, of course, evidence for trapping the singlet. It is not known yet whether this method has general applicability. Besides insertion, singlet carbenes undergo characteristic rearrangements, mainly 1,2-migrations to alkenes if the carbene C(a)-atom is adjacent to a saturated C(/?)atom (see Scheme 8-27, after Nickon, 1993).

(8-27)

M = migrating group; T = group at terminus = bystander group (can be same or different)

340

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

There are two basic problems in these migrations: (1) Two or three different substituents at the C(/?)-atom or substituents at the terminal group (T) may compete for migration, and (2) the migration can be influenced by nonmigrating substituents at C(yff) or T (called "bystander" by Nickon). Qualitatively, the sequence C6H5 > H > CH3 for the migratory ability has been known for a long time (see example in Sect. 8.1, Scheme 8-6). Nickon developed a method to describe the influence of bystanders in a quantitative way using a bystander assistance factor X, symbolized by B[X] *. The definition of the rate constants for propylidene (8.42) and Xsubstituted propylidenes (8.43 and 8.44) is given below these formulae. If the rate constants for H-migration in propylidene (A:H), for C- and H-migration in the substituted propylidenes (formulae 8.43 and 8.44, with kx and £Ha> respectively) are known, they allow calculation of B[X], as shown below 8.44. Of course, all rates must be determined under the same reaction conditions. For example, when X = C6H5, the carbene 8.45 gives $6% 1-phenylprop-l-ene (8.46) and 14% 3-phenylprop-1-ene (8.47) if the carbene was obtained at 150 °C from the 1-phenyl-propan2-one 4-toluenesulfonylhydrazone salt under aprotic conditions (Bamford-Stevens reaction, 8-28, experimental data after Seghers and Shechter, 1976). After statistical correction (2 Ha vs. 3 Hb), one obtains a bystander assistance factor B[Ph] of 9.2**. This factor can be further separated into the corresponding factors for the (E)- and (Z)-alkene formed, B[Ph£] = 7.4 and B[Phz] = 1.8.

ty

VA

V^.

CH2—C^

CH2—C^

CH3

8.42

X—C —C \H

CH3

8.43

/CH = M[H]

X —CH 2 —C —CH3

8.45

8.44

kx = M[X]

+-

^

X —CH=CHCH3

8.46

= M[H]- B[X]

+

X —CH2CH=CH2

(8-28)

8.47

Using this type of evaluation, Nickon (1993) calculated the bystander assistance factors B[X] given in Table 8-1 for aprotic Bamford-Stevens reactions at 150 ± 10 °C (experimental data from various sources). These factors show, for example, that the bystanding methoxy group is overall (i. e., B[X]) more powerful than the methyl group but that this dissimilarity manifests itself only in the B[XZ] array, not in the formation of the (E)-alkene (B[X^]). This result may be due to an entropy effect (see Moss et al., 1992). Most interesting is, * More generally, B[X]M (M = migrating group). If M = H, the M in the subscript is omitted. ** For details, see Nickon, 1993, p. 85. B[X]-factors for (E)- and (Z)-alkenes are indicated by Nickon with subscripts A (anti) and S (syn). We think this should be changed to (E) and (Z).

8.5 Insertion, Abstraction, and Rearrangement Reactions of Carbenes

341

Table 8-1. Some bystander assistance factors for hydrogen migration in thermally generated carbenes of type 8.43-8.44 (after Nickon, 1993).

X C6H5

CH3 C2H5 CH30

B[X]

B[XE]

9.2

7.4

28.5 32.3 73.5

20.1 26.6 20.3

B[XZ]

1.8 8.4 5.7 53.3

however, the result that the inherent migratory abilities of the three most important groups do not display the known migration order, but that this order is dictated to a large part by the bystander groups. Nickon's treatment can be extended to the migration ratio of axial vs. equatorial H-atoms when cyclohexylidenes rearrange to the corresponding cyclohexenes (see Nixon, 1993). This problem is well known and has also been investigated theoretically. Relatively recent ab initio calculations of Evanseck and Houk (1990) show that the groups not migrating adopt a flattened geometry. This and other conformation adjustments predict that Hax and Heq interact with carbene orbitals to approximately the same extent. Nickon's treatment of some experimental data led to the result that the inherent aptitude of an Hax is about 1.7 times larger than that of the Heq in thermal rearrangements of cyclohexylidenes, but 1.2 in protic reactions (Nickon et al., 1993; Stern et al., 1993). A more detailed discussion of these phenomena is, in our opinion, outside the scope of this book. Nickon's evaluation of bystander assistance in carbene rearrangements allowed some interesting conclusions on the origin of migration abilities. We have, however, the feeling that a number of inexplicable cases may be found because the basis of the evaluation is purely empirical, and not really mechanistic. This opinion is based on observations that demonstrated that, in a number of cases, alkenes formed photolytically from carbene precursors are derived from two competitive mechanisms, namely in part from carbenes and in part from photoexcited states of the nitrogeneous precursors of carbenes or from carbene excited states (see Scheme 8-11 in Sect. 8.2). Such cases leading to a rearrangement were found quite early by Chang and Shechter (1979) and more recently by Seburg and McMahon (1992), by the groups of Jones (Fox et al., 1992), and of Platz (see £elebi et al., 1993, and references therein). If a carbene C-atom and the corresponding C-atom of the carbene precursor compete in migration, it is hardly feasible that these two reactions have the same bystander assistance factor. It may be that this possibility limits the general use of bystander assistance factors. Nickon (1993) does briefly mention this possible limitation. We add to the purely organic carbene rearrangements the reactions of carbenes with molecular oxygen (8-29), because they involve an oxygen rearrangement from the primary O-oxide (8.49) to the dioxirane (8.50), as shown by Dunkin and Shields (1986) for cyclopentadienylidene (8.48). Molecular oxygen is a triplet and, therefore, the reaction of 3C>2 is an exceptional case in the sense that triplet carbenes react faster with 3O2 than singlet carbenes, as

342

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

+ 02 ^— 8.48

L:^^0

—^

^K|

8.49

(8-29)

8.50

shown by Ganzer et al. (1986), Sander (1989), Sander et al. (1990, and further papers of Sander cited therein), by Scaiano et al. (1989) and others. These authors determined the rates of reaction of free carbenes in O2-doped argon matrices at low temperature (33-45 K). The mechanisms and products are shown in Scheme 8-30* (R = H, C6H5, or CF3; R' = C6H5, 2-ClC6H4, or CF3).

(8-30)

ot We add to these investigations a recent study of Tomioka's group (Hirai et al., 1994), in which reaction of O2 was used for trapping a triplet carbene and where it was possible to observe the triplet carbene at ambient temperature by laser flash photolysis. (2,4,6-Tri(ter^butyl)phenyl)phenyldiazomethane (8.51) afforded photolytically 4,6-di(ter^butyl)-l,l-dimethyl-3-phenylindan (8.53) almost quantitatively. It is an insertion of the intermediate carbene into a CH bond of the tert-butyl group at C(2). No solvent adducts were found in benzene, cyclohexane or methanol. As * This scheme is a slightly modified version of Scheme 2 of Sander et al. (1990). In part, spin states of metastable intermediates and excited states are tentative.

8.5 Insertion, Abstraction, and Rearrangement Reactions of Carbenes

343

indicated in Scheme (8-31), irradiation at 266 nm suggests that the singlet carbene 8.52 may be involved. In the presence of benzophenone (BP) as a triplet sensitizer, irradiation at 355 nm also yields the indan derivative 8.53, but only in the absence of oxygen. In the presence of O2 the triplet carbene (8.54) is trapped and forms the carbonyl oxide 8.55. These observations indicate that the singlet 8.52 generated by direct irradiation is trapped almost instantaneously by the tert-butyl group before it undergoes intersystem crossing. Sensitized photolysis of 8.51, however, generates the triplet more effectively. It also forms the indan, either directly or via the reverse intersystem crossing. Laser pulse spectra evaluations allow determination of the triplet

(8-31)

8.55

8.53

344

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

lifetime to be ca. 120 ^is. The spectrum of the triplet (340 nm) is similar to that obtained during the photolysis of 8.51 in a 2-methyltetrahydrofuran glass at 77 K. In the context of this investigation of the reaction of (2,4,6-tri(tert-butyl)phenyl)phenyldiazomethane with O2, we will mention first some triplet lifetimes of other diphenylcarbenes, and afterwards we will discuss briefly an intramolecular oxidation of a phenylcarbene. Thanks to the use of laser flash photolysis, Nazran and Griller (1983, 1984) were able to demonstrate that the lifetime of the diphenylcarbene triplet (1.7 \is) is significantly shorter than that of its 2,2/,4,4/,6,6'-hexamethyl derivative (200 jas). Tomioka et al. (1992 a) showed that the lifetime of the hexachlorodiphenylcarbene is 18 ms. The lifetime of decafluorodiphenylcarbene triplet was estimated to be ca. 1 jus at 10 K by Tomioka et al. (1993). An interesting intramolecular oxidation was found by Tomioka et al. (1992 b) when studying the photochemistry of (2-nitrophenyl)diazomethane (8.56) in an argon matrix at 10 K. Irradiation at A > 350 nm provided 2-nitrosobenzaldehyde (8.57), presumably as a result of intramolecular reduction of the nitro group with the neighboring carbene center (8-32)*. .CHO (8-32)

8.56

As reactions of carbenes in organic glasses were discussed in this and other sections of this chapter we close this section with a short reference to a very interesting review of Tomioka (1994) of which we became aware when this chapter was already submitted to the publisher. Tomioka emphasizes strongly a caveat against extrapolations from solution results and from liquid phase mechanistic rules to matrix conditions. This can be shown, for example, in the stereospecificity of cyclopropanations of insertion products into the allylic CH bonds of alkenes. Studying Tomioka's review is clearly a must for all chemists who work with carbenes in a matrix!

8.6 Carbenes from a-Diazocarbonyl Compounds: The Wolff Rearrangement and the Arndt-Eistert Reaction In the thermal, photochemical or metal-catalyzed dediazoniation of a-diazocarbonyl compounds, ketenes are usually, but not always formed. The reaction is known as the Wolff rearrangement, because it was discovered by Wolff early in this century For consecutive photochemical reactions of 8.57, see Tomioka's paper.

344

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

lifetime to be ca. 120 ^is. The spectrum of the triplet (340 nm) is similar to that obtained during the photolysis of 8.51 in a 2-methyltetrahydrofuran glass at 77 K. In the context of this investigation of the reaction of (2,4,6-tri(tert-butyl)phenyl)phenyldiazomethane with O2, we will mention first some triplet lifetimes of other diphenylcarbenes, and afterwards we will discuss briefly an intramolecular oxidation of a phenylcarbene. Thanks to the use of laser flash photolysis, Nazran and Griller (1983, 1984) were able to demonstrate that the lifetime of the diphenylcarbene triplet (1.7 (is) is significantly shorter than that of its 2,2',4,4',6,6'-hexametriyl derivative (200 us). Tomioka et al. (1992 a) showed that the lifetime of the hexachlorodiphenylcarbene is 18 ms. The lifetime of decafluorodiphenylcarbene triplet was estimated to be ca. 1 jus at 10 K by Tomioka et al. (1993). An interesting intramolecular oxidation was found by Tomioka et al. (1992 b) when studying the photochemistry of (2-nitrophenyl)diazomethane (8.56) in an argon matrix at 10 K. Irradiation at A > 350 nm provided 2-nitrosobenzaldehyde (8.57), presumably as a result of intramolecular reduction of the nitro group with the neighboring carbene center (8-32)*. CHO (8-32)

8.56

As reactions of carbenes in organic glasses were discussed in this and other sections of this chapter we close this section with a short reference to a very interesting review of Tomioka (1994) of which we became aware when this chapter was already submitted to the publisher. Tomioka emphasizes strongly a caveat against extrapolations from solution results and from liquid phase mechanistic rules to matrix conditions. This can be shown, for example, in the stereospecificity of cyclopropanations of insertion products into the allylic CH bonds of alkenes. Studying Tomioka's review is clearly a must for all chemists who work with carbenes in a matrix!

8.6 Carbenes from a-Diazocarbonyl Compounds: The Wolff Rearrangement and the Arndt-Eistert Reaction In the thermal, photochemical or metal-catalyzed dediazoniation of a-diazocarbonyl compounds, ketenes are usually, but not always formed. The reaction is known as the Wolff rearrangement, because it was discovered by Wolff early in this century * For consecutive photochemical reactions of 8.57, see Tomioka's paper. Diazo Chemistry II: Aliphatic, Inorganic and Organometattic Compounds. By Heinrich Zoliinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

8.6 Carbenes from a-Diazocarbonyl Compounds

345

(Wolff, 1902, 1904, 1912). He realized that diazoacetophenone yielded the expected alcohol (8-33; a) in boiling water, but in the presence of silver oxide phenyl acetic acid (8-33; b). we/*

H5C6—CO—CH2OH

+ N2

H5C6-CO-CHN2 *

(8_33)

50-C

H5C6—CH2—COOH

+ N2

The Wolff rearrangement of a-diazocarbonyl compounds (8.58, R = H, alkyl, aryl, OR) has great synthetic importance because in most cases the ketenes formed react smoothly with water, alcohols, and amines (Scheme 8-34). An early application that still has considerable importance is the homologization of carboxylic acids (Arndt-Eistert reaction; Arndt and Eistert, 1935). As shown in Scheme 8-34, the reaction starts from the chloride of the acid RCOOH, which leads to an a-diazo ketone with diazomethane (R' = H), followed by the Wolff rearrangement and the hydrolysis of the ketene intermediate to give the homologous carboxylic acid (8.59, R' =H). In alcohols and amines esters (8.60) and amides (8.61, R' = H), respectively,

s~

RR'CH—COOH 8.59

8.60 8 58

-

|

HNR-R'^

RR'CH—CONR"R'"

8.61

C—OH

8.63

(8-34)

346

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

are obtained. Cyclic a-diazo ketones (8.58, R-R') are subject to ring contraction, a reaction that has some importance in synthesis (8.62). The phototransformationof2,l- and 1,2-naphthoquinonediazides* into the corresponding indene-3carboxylic acids (8.63) is a related ring contraction that also proceeds via Wolff rearrangements (see Zollinger, 1994, Sect. 10.13) and that has numerous applications in imaging technology (see Reiser, 1989, p. 409; Zollinger, 1991, Sect. 14.8; and Reichmanis, 1993) and recently also in KrF excimer laser resists (see Horiguchi et al., 1990). This ring contraction was discovered by Siis (1944). At that time, Stis assumed that indene-1-carboxylic acid is formed by the photolysis of 2,1-naphthoquinonediazide. Only in the 1970's, was it found that it is the 3-isomer (see discussion in Zollinger, 1994, p. 285). Kresge's group (Andraos et al., 1994) was able to show that the 1-isomer is also formed and that the failure of previous investigations of the photolysis reaction to detect it is due to the facile isomerization to the 3-isomer and the preponderance of the latter at equilibrium (K= [3]/[l] = 100-300, depending on reaction conditions). Scheme 8-34 also contains the formation of 2,3-bis(trifluoromethyl)oxirene (8.64), which was found by the group of Strausz (Torres et al., 1983) in the photolysis of l,l,l,4,4,4-hexafluoro-3-diazobutan-2-one (8.58, R = R' = CF3) in an Ar matrix. Both the primarily formed ketocarbene and the oxirene could be observed directly. This is an important result in the context of the mechanism(s) of the Wolff rearrangement. Further reactions that may take place under Wolff conditions, are - among others — dimerization to lactones (8.65, Yates and Clark, 1961; Huisgen et al., 1964a), oligomerizations (e.g., Quintana et al., 1973), and the insertion reactions discussed in Section 8.5. Insertions of ketocarbenes into C-H and X-H bonds have been described by Adams and Spero (1991). There are many other applications of ketenes and ketocarbenes obtained as transient intermediates in Wolff rearrangements. Particularly important are reactions allowing the synthesis of novel mono- and polycyclic ring systems. A fundamental example is the formation of cyclobutadiene by matrix photolysis of cyclopropenyldiazo ketone to cyclopropenylketene, which undergoes decarbonylation to form cyclobutadiene (8-35, Maier et al., 1984), and the photodecomposition of l,3-bis(diazo)indan-2-one (8.66), which Tomioka and coworkers converted in an argon matrix at 10 K to the tricyclic cyclopropenone derivative 8.68 (Murata et al., 1993b). The two diazo groups of 8.66 are cleaved stepwise in solution and in matrices at 10 K. It is interesting that in the photolysis of the first diazo group no Wolff rearrangement occurs in solution or in an argon matrix doped with O2, but the ketocarbene formed can be detected at 10 K, as well as the diazoketene 8.67 and the cyclopropenone 8.68 (Scheme 8-36). The large variety of products related to photolysis and thermal dediazoniations of diazo ketones is documented in a recent investigation of Padwa et al. (1993 b) of alk-2-enyl- and alk-2-ynyl-substituted a-diazoacetophenones. Thus, the photolysis of a-diazo-2-ethenylacetophenone (8.69) resulted in the formation of 2-naphthol (8-37, * These compounds are also called diazonaphthoquinones.

8.6 Carbenes from a-Diazocarbonyl Compounds

347

HX

L>=°

-N2 M2

8.66

8.67

(8-36)

8.68

(8-37)

8.70

8-71

yield). Thermolysis, however, produced besides 2-naphthol (50%) 25% of ljFf-lfl,2-dihydrocycloprop[fl]inden-2-one (8.71). This is a nice example of competition of the Wolff rearrangement yielding 2-naphthol and intramolecular cyclopropanation of the initially generated keto carbene 8.70. The related 2-alkynyl-substituted a-diazoacetophenone derivative 8.72 gives the corresponding naphthol derivative 8.73 (8-38). This is, however, only the case if the

(8-38)

8.72

348

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

a-methyl group is present. Without this group, i. e., compound 8.74, a completely different reaction is found, namely dimerization involving a 1,3-dipolar cycloaddition followed by a proton shift to a transient pyrazole derivative (8.75), which undergoes insertion with the neighboring diazo group to give 8.76 (8-39).

(8-39)

8.76

If the phenyl group is replaced by the groups - CH2 - CH2 - C6H5 (8.77) or -CH 2 -O-C 6 H 5 (8.78), photolysis of these diazo ketones yields 7,8-dihydrobenzo[c]phenanthren-6-ol (8.79), and 6/f-benzo[b]naphthol[l,2,-rf]pyran (8.80), respectively (8-40). Padwa et al. (1993 b) also investigated the products obtained when these alkeneand alkyne-substituted a-diazobenzophenones were decomposed catalytically by

(8-40)

8.77

X = —CH2—

8.79

8.78

X = — O—

8.80

8.6 Carbenes from a-Diazocarbonyl Compounds

349

dirhodium tetraacetate, and again different products were obtained. This paper clearly demonstrates, therefore, how diverse products may be obtained from these substituted a-diazoacetophenones by the three reaction conditions, thermal, photolytical, and catalytic. It can hardly be said that these products were predictable! Another method for the synthesis of highly substituted polycyclic aromatic and heteroaromatic compounds was found by Danheiser et al. (1990 b). As shown in Scheme 8-41, the process starts from the unsaturated a-diazo ketones (8.81), from

(8-41)

which unsaturated ketenes (8.82) are formed in a photochemical Wolff rearrangement. The ketene combines with an alkyne in a regiospecific [2 + 2] cycloaddition resulting in a cyclobutenone *. By a 4n electron electrocyclic cleavage an enylketene is produced and it undergoes a 671 electrocyclization to afford the phenol (8.83) via the corresponding cyclohexa-2,4-dienone. This cascade of reactions takes place in 1,2-dichloroethane at 107 K (later room temperature). Yields for 17 different entries are between 31 and 64%. An impressive example for a reaction with a heteroaromatic diazo ketone is the synthesis (8-42) of the marine carbazole alkaloid hyellazole (8.84). For the synthesis of starting materials, Danheiser's method was used (Danheiser et al., 1990a; see Sect. 2.6, Scheme 2-55). The wide applicability of such processes to organic synthesis including that of natural products was summarized by Ye and McKervey (1994). The plenitude of reactions in Scheme 8-34 explains the fact that yields and ratios of products in Wolff rearrangements vary widely. They depend very much on the * Examples of analogous [2 +2] cycloadditions of ketenes with alkenes in photolytic Wolff rearrangements have been known since 1964 (Masamune and Castellucci; see references given by Danheiser et al., 1990b, footnote 11).

350

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates O

1. CH^C=COCH3 2. (CF3S02)20

(8'42)

X = OH 8 84

-

X = OS02CF3

specific type of a-diazocarbonyl compound (substituents R and R/, ring size and stiffness of R — R' etc.) and on the reaction conditions (thermal, photolytic, catalytic, solvent, temperature, etc). This is also the case for the mechanism. A large number of experimental and theoretical investigations have been carried out, but the mechanism is still being debated. A summary is given in Scheme 8-43. Dediazoniation and the 1,2-rearrangement may occur in a concerted manner or in two or three steps via the ketocarbene, the diazirine, or the oxirene. The intermediacy of the diazirine is rarely observed, e.g., by Rau and Bokel (1990; for a summary of earlier work see Lewars, 1983, p. 528). ...

-N2

(8-43) /

"'

-N

R

\

products (see 8-34)

8.6 Carbenes from a-Diazocarbonyl Compounds

351

The C2RR'O potential energy hypersurface includes oxirene, the ketocarbene, and the ketene in (8-43 ; R = R = H). It has been studied very recently in a joint investigation by the groups of Radom and Schaeffer (Scott et al., 1994) with ab initio methods incorporating high levels of electron correlation and basis sets that include up to f and g functions. The mesomeric structures of a-diazocarbonyl compounds (8.85a-8.85c) demonstrate that they are more stable than unconjugated diazo compounds and that the rotation around the central C - C bond is restricted. In the presence of bulky substituents, the coplanarity is no longer optimal, the compounds are accordingly less stable, and ketene formation occurs at lower temperature (see later in this section).

// 8.85a

8.85b

8.85c

As a result of this restricted rotation, the two conformers 8.86 and 8.87 can be observed in !H NMR spectra (Kaplan and Meloy, 1966). The barrier for interconversion is 64.8 kJ mol"1, and 92% of the equilibrium mixture is the S-c/s-conformer 8.86 (R = CH3, R7 = H). Tomioka et al. (1980 a) showed that 8.86 is more reactive in the Wolff rearrangement.

(8-44) N2 8.87

Wolff's discovery in 1902-1912 was accomplished by using thermal and silvercatalyzed conditions. Photochemical Wolff rearrangements were discovered only 50 years later (Homer and Spietschka, 1952). During the last 40 years, more preparative and mechanistic work was made under photolytic conditions. Nevertheless, we will discuss first mechanistic investigations of the thermal method. Thermal rearrangements are kinetically first order with respect to the a-diazocarbonyl compound (Jugelt and Schmidt, 1969) and they are little influenced by solvents or nucleophiles (Bartz and Regitz, 1970). A concerted migration with dediazoniation is unlikely, as the rates do not show a correlation with the migratory abilities of the groups present. These results are consistent with an unassisted rate-determining dediazoniation to the ketocarbene, at least in an aprotic medium. The increase in the rate in the presence of acids and the catalysis by metals, metal oxides, and ions may be due to hydrogen bonding of the carbonyl O-atom and metal complex formation. These effects were examined in a theoretical investigation of Csizmadia's group (Wang et al., 1991). These authors compared the thermal dissociation of diazomethane and 2-diazoacetaldehyde by ab initio computations with 3-21G and 6-31G*

352

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

basis sets and taking into account the correlation energies with an MP4//6-31G* calculation. The carbonyl group in 2-diazoacetaldehyde has the effect that the N — C — C group is no longer linear. This makes the dediazoniation a process that is close to a single-bond cleavage, i. e., to an energetically favorable process. Jugelt and Schmidt (1969) also investigated the influence of substituents in 4- or 4'-position of l-diazo-l,2-diphenylethanone ("azibenzil"; 8.88, either X or Y=H). The Hammett reaction constant Q was found to be 0.75 for substituents X (Y=H). These figures reflect stabilization of the potential negative charge of the nitrogensubstituted C-atom of the a-diazocarbonyl compound and a decrease in the rate of dediazoniation. Electron-donating substituents X stabilize the diazo ketone by conjugation with the carbonyl group.

8.88

For the investigation of the migratory tendency of groups in Wolff rearrangements, the results obtained with unsymmetrically substituted 2-diazo-l,3-dicarbonyl compounds (8.89) are interesting (8-45). Systematic investigations under comparable thermal and photolytic conditions had already been made at an early time (see review of Meier and Zeller, 1975, Table 2), more recently by Tomioka et al. (1983), by Nikolaev et al. (1991, and earlier references mentioned there), by Nikolaev and Popik (1992), Meier et al. (1988), McMahon et al. (1985), and by others. The results demonstrate that the product ratios found for thermolysis and photolysis are in part similar, in part quite different. In general, the migration tendency

(8-45)

8.90

8.6 Carbenes from a-Diazocarbonyl Compounds

353

is high if the migrating group has a high electron density. For thermolysis, the sequence of migration tendency H > C6H5 > CH3 > NR2 > OR was found, but, in photolysis, phenyl and methyl change their positions in that sequence (Meier and Zeller, 1975). Tomioka et al. (1983) and Nikolaev and Popik (1992) showed in series of cyclic and acylic 2-diazo-l,3-diketones that the Wolff rearrangement depends on various parameters. The results indicate that, on the way from planar cyclic to highly skewed acyclic aroylacyldiazomethanes, a concerted Wolff rearrangement turns into a carbenic process. The migration tendency in cyclic 2-diazo-l,3-dicarbonyl compounds was also investigated. The arrows in 8.91, 8.92, and 8.93 indicate the migrating center (after Meier and Zeller, 1975).

/ 8.91

8.92

An interesting comparative study of a cyclic compound with three open-chain 2-diazo-l,3-dicarbonyl compounds was performed by Nikolaev and Popik (1992). In 8.94, the three functional groups are in the S-c/s,S-c/s-conformation, the sixmembered ring is planar. Compounds 8.95 (R = CH3) and 8.96 (R = t-Bu) are S-cis, S-c/s-skewed and the equilibrium mixture of 8.97 +* 8.98 consists of S-cis9S-cis- and S-cis,S-trans-conformers that are strongly skewed. In 8.94, alkyl rearrangement is clearly dominant over aryl migration (> 50:1), in 8.95 it is still dominant (2:1), but, for 8.96, 8.97, and 8.98, it is practically only the aryl group that migrates (< 1:50). The results are the same for thermal and photolytic reactions. Only in the case of 8.96 is a large amount of insertion product found (45-60%, other compounds 0-4%). The authors interpret the results of 2-diazo-l,2,3,4-tetrahydro-4,4-dimethyl-

O S-cis, S-cis 8.94

B-cis, S-ds 8.95 R = CH3 8.96 R = C(CH3)3

S-cis,S-cis

(H3C)3C

354

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

naphthalene-l,3-dione (8.94) by a concerted elimination of N2 and migration, while, for the acyclic nonplanar compounds, the generation of an intermediate diacylcarbene (8.90, in 8-45) is postulated. As indicated earlier in this section, there are still contradictory proposals for the mechanism(s) leading from 2-diazo-l-carbonyl and -1,3-dicarbonyl compounds via Wolff rearrangements to ketenes (Scheme 8-43). Nikolaev and Popik's investigation (1992) demonstrates that compounds that are appearently similar in structure may be characterized by quite different reaction pathways in 8-43. Additional confusion arose by the observation of transient (metastable) intermediates that were assigned to ketocarbene, oxirene, and ketene structures without unambiguous evidence for the structure postulated. First, it has to be emphasized that under specific structural or reaction conditions such intermediates have clearly been observed. This is, for example, the case for the formation of a stable oxirene under Wolff reaction conditions, if the — C(O) —C(N 2 )— moiety is linked to trifluoromethyl substituents on both sides (see 8-34, 8.64, R=R' = CF3; Torres et al., 1983; or for fulvenones, Blocher and Zeller, 1994). These results cannot be generalized, however, because the groups of Zeller and Strausz showed by tracer marking that oxirenes are not in all cases Wolff intermediates (Zeller et al., 1971; Zeller, 1975; Fenwick et al., 1973)*. Analogously, the clear evidence for ketocarbenes as precursors of certain strained ketenes formed on irradiation of diazoketones at low temperature in Ar matrices (McMahon et al., 1985) cannot be interpreted to indicate that mechanisms with "bypasses" around ketocarbenes are impossible (for discussions of bypass mechanisms in Wolff rearrangements see £elebi et al., 1993, and further references therein). Flash photolysis allowed even better detection of transient intermediates but the assignment of structures to any metastable intermediate observed in such an experiment is an additional problem! This fact is demonstrated very well in an investigation of several naphthoquinonediazides by Tanigaki and Ebbesen (1987, 1989). They assigned oxirene and ketene structures to two successively formed transient species. In other studies (Delaire et al., 1987; Shibata et al., 1988), however, the first transient species was assigned as a ketene and the second the structure 8.99, i. e., the water addition product of the ketene**.

8.99

* For a recent theoretical investigation of oxirene stability by Schaefer's group, see Vacek et al. (1991). ** This compound is called ketene hydrate by Barra et al. (1992), but carboxylic acid enol by Andraos et al. (1993).

8.6 Carbenes from a-Diazocarbonyl Compounds

355

Such discrepancies, in my opinion, reflect a lack of intellectual sophistication in the evaluation of experimental observations. Such an approach was basically known in ancient philosophy. In this century, it was developed and advocated in particular by (Sir) Karl Popper in his book The Logic of Scientific Discovery (1959, 1980). Very briefly it says that scientific hypotheses should be verified (experimentally or theoretically), but one should realize that corroboration (verification in Popper's terms) can never be safe against falsifications which, in contrast, can be definite. As discussed in an Interlude in the book on aromatic diazo chemistry (Zollinger, 1994, Chapt. 9), the human mind has a tendency for verification, and hesitates to search for falsification. It is, indeed, very rewarding to see that in a recent joint paper of the groups of Kresge and Scaiano (Andraos et al., 1993) these principles are followed, although Popper or other reference to the philosophy of science is not specifically mentioned. To clarify the confusing situation of hypotheses proposing various transient species in photolyses of naphthoquinonediazides, Andraos et al. carried out a detailed investigation of the flash photolysis of five substituted 1- and 2-diazo-l,2-naphthoquinones in aqueous solution. They observed the formation and decay of two transient species. From the form of acid-base catalysis of their decay and the magnitude of the solvent isotope effects (^H2o/^D2o) as a function of the acidity of the solvent, they reached the conclusion that the first transient is a ketene and the second a carboxylic acid enol (8.99), i. e., the water-addition product of the ketene. In the sense of Popper's ideas, the discussion part of their paper is remarkable because the authors provide arguments against hypotheses that the observed transient intermediates may be ketocarbenes or oxirenes. It must be added, however, that these results do not falsify a hypothesis that ketocarbenes or oxirenes exist as steady-state intermediates, i. e., at concentrations too low to be observed. I close the discussion on that investigation of the groups of Kresge and Scaiano by saying that the paper is a pleasure for a physical organic chemist because it combines in a masterly way modern kinetic methods with interpretations of acid-base catalysis including isotope effects. Two years earlier, Scaiano's group (Barra et al., 1992) investigated the kinetics of the photolysis of l,2-naphthoquinone-2-diazide in acetonitrile as solvent. They found a second-order dependence on the concentration of water added to the acetonitrile. This result is consistent with either 8.100 or 8.101 as transition state between the ketocarbene and the indene-3-carboxylic acid. A differentiation between 8.100 and 8.101 is possible on the basis of theoretical investigations on the addition of water to ketenes. Such nucleophilic additions were =f=

O---H

f^c-cf H*

/

O—H

0---H

3

O—H

V-H' H

H 8.100

8.101

356

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

studied by various authors (see discussion by Seikaly and Tidwell, 1986, and Tidwell, 1995, Sect. 5.5). On the basis of the large coefficient of the LUMO at the C(a)-atom in the ketene plane, one expects nucleophilic attack at this atom. The most reliable results of calculations are likely to be those of Skancke (1992), for the system CH2 = C = O + 2 H2O (gas phase; MP4(SDTQ)/6-31GV/RHF/6-31G* level). On this basis, the transition state for addition of (H2O)2 at the C = O bond (8.101) lies 20 kJ mol"1 below that for addition to the C = C bond (8.100). The activation barriers for the dimer addition are clearly lower («42 kJ mol"1) for both modes of addition than those for the monomer addition. These results indicate that the addition will follow both pathways, with a slight preference for the C = O addition. Comparison of these theoretical with experimental results (Bothe et al., 1980) shows that the latter are lower by 40 kJ mol"1. This result probably indicates that more than two water molecules are involved in the reaction — a result that is not surprising! In a number of Wolff rearrangements, acid or base catalysis was observed. Allen et al. (1992) gave a tentative explanation for these catalyses, as well as for the surprisingly large influence of conjugating substituents like C6H5, (E) — C6H5CH = CH, and C6H5C = CH, which increase the reactivity relative to H by factors of two, three, or four powers of ten. Ene-diols have been observed in the hydration of tri- and pentamethylated diphenylketenes (Allen et al., 1992). In these sterically hindered ketenes, the rate of hydration is independent of acidity between pH 1 and 9; only weak buffer catalysis is observed. As we see these mechanisms today, they were — at least in principle — originally proposed in a contribution of Lacey (1964) to the volume of alkenes in Patai's series Chemistry of Functional Groups, but not considered in many investigations made after 1964. Investigations of cyclic ketenes, like the pentafulvene (8.102), generated photochemically from 2-diazo-l,2-benzoquinone (Urwyler and Wirz, 1990), and its benzo derivative (8.103) (Barra et al., 1992; Andraos et al., 1993, 1994; Almstead et al., 1994) are in accordance with the mechanisms discussed above. Trimethylsilylketene [(CH3)3SiCH = C = O] reacts slower by a factor of 4 x 103. This can be ascribed to the stabilization of the acylium ion by silicon ((CH3)3SiCH2
C=O

8.102

8.103

8.6 Carbenes from a-Diazocarbonyl Compounds

357

2-diazo ketones and of l-diazo-l,2-benzoquinone. The results predict that l-diazo-l,2-benzoquinone and 2-diazoethan-l-one form the ketene in a concerted dediazoniation-rearrangement process, whereas cyclic diazo ketones first form an oxirene. Today, it is probably appropriate to say that, with such a complex process as the Wolff rearrangement appears to be, theoretical investigations should be made at the highly-sophisticated ab initio level in order to lead to conclusive results. An authoritative monograph on the chemistry of ketenes has been written by Tidwell (1995; see also his review, 1990). The Wolff rearrangement has also been reviewed by Maas (1989), Gill (1991), and Ye and McKervey (1994). There is an Organic Syntheses procedure for the thermal Wolff rearrangement of 2-diazo-l,2-diphenylethanone to diphenylketene by Smith and Hoehn (1955) and another procedure for a Wolff rearrangement catalyzed by silver benzoate (Lee and Newman, 1988). There are relatively few recent investigations on the influence of metal catalysts, e.g., by Smith et al. (1984) on copper salts, and by Kropf and Reichwaldt (1992) on silver oxide. This neglect of metal catalysis is surprising, as Wolff discovered the rearrangement of diazo ketones when he used silver oxide as catalyst (see Scheme 8-33). Finally we will discuss briefly the Arndt-Eistert reaction, mentioned already in the context of the general scheme (8-34) of preparative methods. This reaction (1935) is actually a sequence of three reactions, first a nucleophilic substitution of an acyl chloride by diazomethane, followed by a metal-catalyzed Wolff rearrangement, and finally hydrolysis of the resulting ketene. The mechanism of the first of these three steps will be discussed in Section 9.1; the other two steps have been described earlier in this section. In the 1930's and later, but before instrumental analytical methods (IR, NMR, Xray, etc.) were easily available, the Arndt-Eistert reaction was very welcome for the characterization of degradation intermediates of natural products (Bachmann and Stuve, 1942). Bridson and Hooz (1988), and Scott and Sumpter (1993) described processes for the first step, and Lee and Newman (1988) for the overall reaction sequence in Organic Syntheses. The reported yields for both steps are excellent (84-90% each). Larock reviewed various procedures for Arndt-Eistert reactions (including the little investigated metal catalysis) in his book Comprehensive Organic Transformations (1989, p. 933). It is possible to use bis(diazoketones) for the synthesis of bisketenes as well as for Arndt-Eistert reactions. Such cases were studied by Gleiter et al. (1992) and by the group of Prinzbach in the context of dodecahedrane and related syntheses (e. g., Fessner et al., 1983; Melder et al., 1992). An apparently similar reaction to the Arndt-Eistert process is the homologization of aldehydes and ketones by diazomethane. In the IUPAC nomenclature of transformations (1989 c), both are methylene insertions, but the homologization of aldehydes and ketones does not involve a carbene or ketene intermediate. We discussed it therefore in Section 7.7 in the context of dediazoniations via diazonium ions and carbocations. It is worthwhile to draw attention to the early work of Wolff, as mentioned at the beginning of this section. He discussed in one of his early papers the striking fact that, in boiling water, diazoacetophenone yields the expected (at least at that time) product of a hydroxy-de-diazoniation, but, in the presence of silver

358

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

oxide, the acid — even at a lower temperature (50 °C), as shown in Scheme 8-33! For a long time, the cause for this lower temperature was "explained" by the catalytic effect of the silver ion — but it was not until the 1950's that it was realized that the classical hydrolysis was a deamination via a diazonium (zwitter) ion, and that the catalytic version was a carbenic reaction or — considering the catalyst — a process involving a carbenoid.

8.7 Transformations Involving Metal Carbenoids Catalysis of dediazoniation reactions of aliphatic diazo compounds by transition metals has been known since the beginning of this century. The understanding of this catalysis started in 1952, shortly after the concept of carbenes was introduced (see Sect. 8.1). Yates postulated that transition-metal catalysts react with diazo compounds by formation of transient electrophilic metal carbenes, because that complex can be depicted as a metal-stabilized carbocation (8.104). Doyle (1986 a) proposed the catalytic cycle (8-46) for the formation of the carbenoid 8.104 and its reaction with an electron-rich substrate S: . The reagent S: is, first of all, an alkene in cyclopropanation, but can also belong to other groups of compounds, to be discussed later in this section. SCR2

-A V

R2C = N2

L

/^^ 4

8 104

-

<8-46) J

Until the end of the 1970's, interest in such reactions concentrated on catalysis by copper salts (review: Burke and Grieco, 1979), obviously influenced by the long, broad, and successful experience with copper2+- and copper+-ions in aromatic diazo chemistry (Sandmeyer, Pschorr and Meerwein reactions, see Zollinger, 1994, Chapts. 8 and 10). A landmark was the discovery of Salomon and Kochi (1973), who found that cyclopropanations with diazomethane in the presence of copper(i) trifluoromethanesulfonate (triflate;~OTf) resulted in reduction of Cu2+ to Cu + , and that the rate of dediazoniation is inversely proportional to the alkene concentration. These results strongly indicate that formation of an alkene-Cu+ complex (8-47; n ^2) precedes the complex formation with the diazoalkane. In copper chelates like bis(acetylacetonato)-copper(n) (Nozaki et al., 1966), formation of alkene complexes is negligible (at least not detectable). The comparison

8.7 Transformations Involving Metal Carbenoids

359

(R2C=CR2)nCu+ ~OTf

= CR2)n_1Cu+ ~OTf

+ R2C=CR2

(8-47)

(R2C = CR2)n^ Cu — CHR'— N2+ ~OTf

of the effect of this copper chelate with copper triflate in the cyclopropanation of 7-methylocta-l,6-diene (8-48) demonstrates that the reaction involving a catalyst that is capable of forming an alkene-copper complex leads to a higher percentage of cyclopropanation at the less substituted double bond, whereas the reverse regioselectivity is obtained, if a copper chelate is used as catalyst (Salomon and Kochi, 1973).

(8-48)

Palladium(n) and rhodium(n) acetates were introduced by Teyssie's group (Pd: Paulissen et al., 1972; Rh: Paulissen et al., 1973). They differ from one another in their ability to coordinate with alkenes and have, therefore, a different regio- and substrate specificity (Anciaux et al., 1980). Cobalt complexes are first of all interesting because of their effect on enantioselectivity. We will discuss them in Section 8.8. Here, we emphasize only that enantioselectivity provides the most convincing evidence for the involvement of metal-carbene intermediates in cyclopropanations. Stereochemical data support the occurence of these intermediates, as also shown by Doyle et al. (1984b): They compared reactivities and stereoselectivities of cyclopropanations of phenyldiazomethane and eleven different open-chain alkenes containing a terminal double bond or a double bond in the chain, and a cyclic alkene (cyclopentene) catalyzed by the binuclear complex Rh2(OCOCH3)4 (8.127, see later in this section), with the reactivities and stereoselectivities of cyclopropanations of the same alkenes with (benzylidene)(pentacarbonyl)tungsten [(CO)5W(CHC6H5)], i.e., a stable metal-carbene. An almost perfect linear relationship of the cyclopropane derivatives of the eleven alkenes with the two carbene sources was obtained. On this basis, Doyle and his coworkers concluded that the reaction starts with an initial association of the alkene 7t-bond with the electrophilic center of the metal-carbene complex, followed by o-bond formation with backside displacement

360

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

of the catalyst. In cyclopropanations with a-carbonyl diazo compounds, transcyclopropane products are formed preferentially. This can be explained by an interaction of the developing electrophilic C-atom of the original alkene with the nucleophilic carbonyl O-atom, as shown in the transition state 8.105.

8.105

The regioselectivity of cyclopropanations at dienes is a function of electronic influence of the catalyst and of substituents in the diazo compound and in the diene. A transition state 8.106, with little charge development at the alkene bond, is likely to be formed when PdCl2 is used. The latter favors cyclopropanation at the C(3) = C(4) bond of 2-methylbuta-l,3-diene (isoprene), but, when Rh2(OCOCH3)4 is used, by which some charge is developed (transition state 8.107) formation of the cyclopropane ring at the C(1) = C(2) bond is strongly favored (Doyle et al., 1982 b, 1984 a).

V

V

/ \

/ \

\\.-CR2- - -MLn

8.106

t ;

8.107

Stereoselectivity of cyclopropanation with 22 alkenes and regioselectivity of monosubstituted buta-1,3-dienes are highest for a copper(i) catalyst, intermediate for two Rh11 catalysts and lowest for a PdCl2 complex. On the basis of these comparisons, Doyle et al. were able to define and determine simple linear relationships, namely an index S of relative Stereoselectivity (1984 a), and R of relative regioselectivity (1982 b). More data on stereo- and regioselectivities were summarized by Doyle (1986). We shall return to the mechanism of Stereoselectivity of cyclopropanation later in this section in the context of dihydrofuran formation. Yields are, in general, highest with rhodium catalysts. Copper bronze as a suspension was practically the only catalyst for cyclopropanation before the 1960's (see Fuson and Cleveland's Organic Syntheses procedure for its preparation, 1955). It is still used, obviously because it is cheap and easily available. The yields with copper bronze, however, are clearly lower than with Cu- or Rh-catalyst in a homogeneous system: Doyle (1986, Table I) found four cyclopropanations described in the literature that were conducted under heterogeneous (Cu bronze) and homogeneous

8.7 Transformations Involving Metal Carbenoids

361

catalysis (Cu and Rh compounds). The average yield of the four heterogeneous reactions was 61%, that of the homogeneous processes 82%. A very impressive comparison of yields in cyclopropanations of a large number of alkenes with methyl and ethyl diazoacetate under identical reaction conditions, but with three different catalysts, namely copper(n) triflate, palladium(n) diacetate, and dirhodium(n) tetraacetate, was made by Anciaux et al. (1980). They demonstrated that the rhodium catalyst gives the highest yield in 17 out of 20 cases; the palladium catalyst is better in three cases, and copper triflate is lower, except in one case in which it equals the result with the rhodium catalyst. Maas (1987, p. 85 ff.) reports in his review on other comparisons beside that of Anciaux and coworkers; in the large majority of cases, the rhodium-based catalyses tabulated in that review are shown to be optimal. We will return to comparisons of catalysts in the context of selectivities later in this section. We should mention, however, that Doyle (1986) found three relatively old patents of large chemical manufacturers for the continuous production process of ethyl chrysanthemate (8.108), using copper bronze (Shim and Martin, 1970; Nurrenbach and Boll, 1974; Milner et al., 1978)*. For a continuous process, a heterogeneous catalyst has certain advantages. On the basis of an enquiry that we made in 1992 by six large manufacturers concerning the use of diazoalkanes in general for large scale production, we have doubts whether the three patents mentioned really became the basis of a commercial process.

A critical factor for the undoubtedly most interesting group of catalysts for the reactions of carbenoids, the rhodium complexes, is the price of rhodium. In 1993, it was US$ 1500 per Troy ounce ($ 50 per g), i.e., fourteen times higher than that of copper**. Therefore, soluble rhodium carboxylates of terminally functionalized poly(ethenecarboxylic acids) have been developed recently (Bergbreiter et al., 1991; Doyle et al., 1992a). They are effective and recoverable cyclopropanation catalysts. Alkoxyalkenes (alkyl vinyl ethers, 8.109) form dihydrofurans with various diazocarbonyl compounds, e.g., ethyl 3-diazo-2-oxopropionate (diazopymvate, 8.110) in the presence of copper and rhodium catalysts (see Wenkert et al., 1977, * More recently, Yadav et al. (1989) synthesized (IR )-c/5-chrysanthemic acid from (R,R )-tartaric acid with copper acetoacetate as catalyst. It is a valuable intermediate for the synthesis of pyrethroids (see also Franck-Neumann et al., 1985, and Krief et al., 1988). ** The price of rhodium is also a problem for catalytic converters in car exhaust technology where combinations of three expensive platinum-group metals are used — Pd, Pt, and Rh. As a result, Allied Signal developed Pd-only catalysts in recent years.

362

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

1978, 1981; Alonso et al., 1983, and the extensive discussion in the review of Maas, 1987, p. Ill ff.). The variation of substituents in the investigation of reaction 8-49 in boiling benzene by Alonso et al. (1983) demonstrates the broad applicability of this process: R=H, CH3, C2H5 or C6H5; R' = H or CH3; R and R' = -(CH 2 ) 5 -; R" = H or C6H5; and R'" = CH3, C2H5, C4H9. 2-Diazo-l,3-dicarbonyl compounds such as 3-diazopentadione (8.111) and 2-diazo-3-oxobutyrates (8.112) can also be used, but diazo esters cannot (Wenkert et al., 1977; Alonso et al., 1982). R-

R N

„/

/

„,

\

I

8.109

o H3(T

o >< N2 8.111

o "CH3

H3CT

^

"OR

N2 8.112

Alonso et al. (1983) also studied the regio- and stereoselectivity of these reactions. Interesting reagents are 1- and 2-methoxybuta-l,3-diene. As shown in (8-50), l-methoxybuta-l,3-diene (8.113) reacts with high selectivity at the unsubstituted double bond, whereas, with the 2-methoxy isomer (8.114), cycloaddition at the more electron-rich double bond is the main reaction (8-51). There are also cases known from the series of reactions with substituted alkoxyethenes (8.109), which show that these cycloadditions proceed stereospecifically; the configuration of the dihydrofuran corresponds to that of the alkoxyethene. Furans may be formed in the reaction with metal carbenoids derived from diazocarbonyl compounds, if alkynes are used instead of alkenes. Furan formation is particularly favored when the carbenoid is a 3-diazo-2-oxopropionate (e.g., 8.110, Wenkert et al., 1983) or contains two electron-withdrawing groups (see Davies and Romines, 1988) and when electron-donating groups are present in the alkyne. Davies

8.110

8.113

8.7 Transformations Involving Metal Carbenoids

363

H3cq 8.110 Rh2(OCOCH3)4

OCH3

9 :1

8.114

et al. (1992c) described the synthesis of ethyl 2-methyl-5-phenylfuran-3-carboxylate (8.115) using Rh2(CH3COO)4 as catalyst in an Organic Syntheses procedure. These dihydrofuran syntheses may be considered as 1,3-dipolar cycloadditions because the ketocarbene (8.117 a) formed in the reaction of diazocarbonyl compounds (8.116), like 8.110, with metal complexes has dipolar character (8.117b).

COOC2H5 8.115

(8-52) 8.116

8.117a

8.117b

There is no doubt that such a ketocarbene is expected to be a 1,3-dipole, as discussed in Section 6.2, but the process 8-52 is not a carbeno/d reaction, as shown in Doyle's general scheme 8-46. The dihydrofuran syntheses are, therefore, only apparently dipolar cycloadditions. Doyle et al. (1984b) suggested a mechanism for these cycloadditions that is closely related to his explanation of the preferential transstereoselectivity in cyclopropanation by a-carbonylcarbenes. One argument of Doyle for this conclusion is the close analogy between the results of dihydrofuran formation of 1- and 2-methoxybuta-l,3-diene with ethyl 3-diazo-2-oxopropionate (8.110) and the cyclopropanation of these butadiene derivatives with ethyl diazoacetate (Doyle et al., 1981, and other papers; see Maas, 1986, p. 97). We return, therefore, to the transition state of cyclopropanation (8.105) here in order to investigate whether it is consistent with the mechanism of formation of dihydrofuran. Doyle's transition state for the cyclopropanation of alkenes with ethyl diazoacetate is a basis for the apparently completely different reaction with diazocarbonyl compounds that leads to dihydrofurans. Structure 8.105 shows the cyclopropanation process after the reaction of diazoacetate with a transition-metal complex. The essential phenomenon is that, as a nucleophile, the carbonyl group of the diazoacetate in-

364

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

fluences the association between the reacting ethene and the electrophilic carbene. The scheme predicts that increasing the size of the ester group should lead to an increase in taws-selectivity. This is indeed the case, if the selectivity of the reaction with ethyl diazoacetate is compared with that of l-isopropyl-l,2-dimethylpropyl diazoacetate. 7V,7V-Dimethyldiazoacetamide is also a more selective reagent, not for steric reasons, but because its carbonyl group is a better nucleophile (Doyle, 1986, p. 928, where further evidence for the mechanism is discussed). As mentioned above, dihydrofurans were not found in reactions of diazoacetates with alkoxyalkenes. This observation was the basis for Doyle et al. (1984 b) to postulate that increased stabilization of the bond between the O-atom of the carbonyl group and the electrophilic center of the original alkene will favor formation of the dihydrofuran products. This is shown in Scheme 8-53, which is a bifurcation afte^ the transition state 8.105.

(8-53)

»-H I

M

"

'H

hi

"

CH3

The third group of transformations involving metal carbenoids of aliphatic diazo compounds are insertions into C —H, N —H, and other bonds. Although known since the 1950's, using copper catalysts (see review of Burke and Grieco, 1979), these insertions have become a significant contribution to organic syntheses only since Teyssie's group found that rhodium compounds are much better catalysts for insertions than copper bronze and copper complexes (Demonceau et al., 1981, 1984). The selectivity of CH insertion normally increases in the sequence primary < secondary < tertiary C —H bonds, corresponding to the electrophilic character of carbenoid reagents (Demonceau et al., 1984). Intramolecular CH insertions with rhodium catalysts are synthetically important. Acyclic diazo compounds containing aliphatic chains yield in most cases fivemembered rings, e.g., in (8-54) the taws-cyclopentanone 8.119 is formed diastereoselectively in 11% yield (Taber and Ruckle, 1986). The diazoketo ester 8.120 containing an alkyl chain with a terminal C = C bond leads to the cyclopentanone 8.121 in 62% yield (8-55), which demonstrates that the insertion dominates an intra- or intermolecular cyclopropanation, as found by Wenkert's group (Checcherelli et al., 1990).

,COOCH3 (8-54)

8.118

8.119

8.7 Transformations Involving Metal Carbenoids

365

(8-55)

8.120

8.121

Scott and Sumpton (1993) described an Organic Syntheses procedure in which l-diazo-4-phenylbutan-2-one (8.122) is used for a cyclization. Compound 8.122 is comparable, to a certain extent, to the diazoketo ester 8.118, as there is also an alkyl chain between the diazo group and a phenyl substituent. As shown in Scheme 8-56, the reaction is, however, different, as, in addition to a cyclization, a ring enlargement of the benzene ring takes place. The primary product 8.123 is unstable and forms 3,4-dihydro-2//-azulen-l-one (8.124).

(B-S6)

8.122

8.123

8.124

CH insertion also works for the synthesis of lactones, particularly of y-butyrolactones. Interesting cases demonstrating the importance of the Rh ligands for the CH insertion selectivity were found by Doyle et al. (1989b; see also Doyle's review, 1992). They compared binuclear rhodium complexes of type 8.125 with four bridging carboxylate and carboxamide ligands, namely the tetraacetamide [Rh2(HNCOCH3)4] (8.126), the tetraacetate [Rh2(OCOCH3)4] (8.127), and the tetraperfluorobutyrate [Rh2(OCOC3F7)4] (8.128). The arrows in formula 8.125 indicate the two unsaturated (electrophilic) centers of the dirhodium-tetracarboxylate catalysts. They used these three catalysts for lactonization (8-57) of the two diazo esters 8.129 (Z = H and COCH3). The results demonstrate that the rule for the sequence of reactivity of primary, secondary, and tertiary C - H bonds (mentioned above) has

R 8.125

366

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates CH3

cT I/

CH3

C3F7

cr ^o I/ I/

I/

8.126

o

8.127

o

8.128

"V^ .^-W,

-=^-

. -Vy-W

'^J^ H3C^ ^CH3

8.129

8.130

<™

H3C H3CX

"CH3

8.131

Z = H or COCH3

only a limited validity. With the perfluoro catalyst [Rh2(pfb)4] (8.128), indiscriminate CH insertion occurred with both diazo esters and total yields were relatively low (45-56%). The two other catalysts gave higher total yields (81-97%), and in part, very different ratios of the two isomers 8.130 and 8.131. Dirhodium tetraacetamide (8.126) had a very high selectivity in favor of the tertiary CH group, i. e., > 99% 8.130 for both diazo esters 8.129. Dirhodium tetraacetate (8.127) showed good selectivity for the tertiary CH group (8.130) only with the diazo ester containing an additional carbonyl group (8.129, Z = COCH3, ratio 8.130:8.131 = 90:10), but was not able to discriminate products for the other diazo ester (8.129, Z = H, ratio 8.130:8.131 = 53 :47). The influence of a change of substituent in the or-position to the diazo group was also demonstrated by Doyle's group for syntheses of /Mactams (Doyle et al., 1988, 1989 c). Treatment of some substituted 7V-benzyl-7V-(^r^-butyl)diazoacetoacetamides (8.132, R=COCH 3 ) with dirhodium tetraacetate (8.127) in refluxing benzene resulted in the exclusive formation of frwzs-disubstituted /Mactams 8.133 in excellent yield (8-58). The same reactions, but with the corresponding acetamides (8.132, R = H), lead to products of insertion into the neighboring aromatic ring (8.134), albeit under different reaction conditions (CH2C12, room temperature). These unexpected results were rationalized and extended to related systems by Doyle (see his review, 1992), but we do not discuss his explanations here because this would require too much space, as other experimental data must be included. More recently, Doyle et al. (1993 a) also investigated the effectiveness of various rhodium catalysts with chiral ligands for enantiocontrol in CH insertion reactions (see Sect. 8.8). Padwa's group (Brown et al., 1994) has recently published a broad investigation on the cyclization reactions of ethyl 7V-benzyl-2-diazo-7V-phenylmalonate amide (8.135) and related a-diazoamides. The results demonstrate that, when using a new

8.7 Transformations Involving Metal Carbenoids

367

(8-58)

8.134

catalyst dirhodium tetra(perfluorocarboxamide), the main product is ethyl 1-benzyl2,3-dihydro-2-oxoindole-3-carboxylate (8.136), whereas with dirhodium tetraacetate (8.127) ethyl l,4-diphenyl-2-oxoazetidine-3-carboxylate (8.137) is obtained (8-59).

(8-59)

8.136

NH insertions were already known at the time of the exclusive use of copper catalysts for metal-carbene transformations, but, like CH insertions, they became important in synthesis only at the time of growing interest in rhodium catalysts. A breakthrough was the intramolecular carbenoid insertion into the NH bond of azetidin-2-one, catalyzed by [Rh2(OCOCH3)4] (8.127), as it was first described for the synthesis of thienamycin (8.140) by the group of Salzmann (1980) in the Merck laboratories. This synthesis (8-60) opened the way for many related pharmaceutical products of the carbapenem and the carbacephem type (see Maas, 1987, Table 21, p. 201). At an early date, the NH insertion of the parent compound 8.141 was studied

368

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

Rh2(OCOCH3)4

(/

J_N ^k H N2^COOpNB

N

/'

H3C

- 2

//—N

0^

8.138

//

^

(8-60)

HOA

H3c

^

C/

^ COCT

8.141

8.140

by four groups (Ratcliffe et al. , 1980; Kametani et al. , 1981 ; Berges et al. , 1981 ; Ueda et al., 1983). It is interesting that the intramolecular insertion from 8.138 to 8.139 gives a quantitative yield and that only the more stable feto-compound 8.139 is formed. Intramolecular carbenoid insertion into NH bonds of diazohydrazides of type 8.142 is also possible, as shown by Lawton et al. (1987). In boiling benzene, diazetidine-l,2-diones (8.143) are obtained in good yield (87-93%), if dirhodium tetraacetate is used as catalyst (8-61).

<8-61)

R = C0H5, R' = CH2COOC2H5, OCOCH2C6H5

OH and SH insertions are also known. They are used for the synthesis of aalkoxyketones by reaction of a-diazocarbonyl compounds with alcohols, and for the synthesis of a-phenylthioketones, using thiophenol (see review of Maas, 1987, p. 204). Ylide generation from diazo compounds by reaction of carbenoids is a better method than photochemical or thermal dediazoniation in the presence of organic substrates containing heteroatoms, because these dediazoniations without metal catalysis yield, in most cases, not very selective carbenes. Here again, the coppercatalyzed route is in most cases inferior to that with rhodium catalysts. The diazoketo ester with a terminal thioalkyl group (8.145) can be obtained from the

8.7 Transformations Involving Metal Carbenoids

369

thiolactone 8.144 and lithiodiazoacetate, followed by in situ alkylation. Under rhodium catalysis in boiling benzene, it forms the cyclic sulfonium ylide 8.146 (8-62) (Moody and Taylor, 1988), which depending on the character of the alkyl group R, undergoes various reactions (Stevens 1,2-rearrangement, 2,3-sigmatropic rearrangement, or fragmentation at the C —R bond). 1.

8.144

H£2OOCX /Li jf N2

8.145 j

(8-62)

Not only compounds with thioalkyl groups, but also those with aliphatic or aromatic sulfine groups react intramolecularly with carbenoid groups, as the examples in Schemes 8-63 and 8-64 demonstrate (Moody et al., 1988). In these reactions, cyclic sulfoxonium ylides are obtained. 1,3-Dipoles can be synthesized by intramolecular carbenoid dediazoniations. They were investigated first of all by Padwa's group (Padwa et al., 1988a, 1988b, 1989a,

(8-64)

370

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

1989b, 1992; Padwa and Zhi, 1990; reviews: Padwa, 1991 c, 1993; Padwa and Hornbuckle, 1991; Padwa and Krumpe, 1992). These reactions present an interesting combination of two major subjects of this book, namely metal carbene transformation (Sects. 8.7-8.8) and 1,3-dipolar cycloadditions (Chapt. 6). Basically, they are rhodium-catalyzed reactions of a-diazo ketones in the presence of various heteroatoms. In the most interesting cases, the heteroatom is bound to a substituent of the a-diazo ketone and the initially formed dipole compound reacts with a dipolarophile A=B (8-65). If diazoimides of type 8.147 are used instead of diazoketones, representatives of so-called isomunchnones (8.148; Scheme 8-66) are formed (see Hertzog et al, 1992, and other papers of Padwa and coworkers mentioned there). They are interesting synthons for the preparation of bi- and tricyclic heterocycles (e.g., Padwa and Hertzog, 1993).

(8-65)

(8-66)

Another 1,3-dipole with properties that are representative for such compounds (see Sect. 6.2) is 8.150, which can be obtained by [Rh2(OCOCH3)4] catalysis from the a-diazoacetophenone derivative 8.149 (Padwa et al., 1988a). The 1,3-dipole reacts easily in an intramolecular fashion to form the tetracyclic compound 8.151. The dipole can, however, be trapped by dimethyl ethynedicarboxylate and the tricyclic compound 8.152 is isolated. From a structural chemistry point of view the synthetically complex products that Padwa's group obtained in all cases (see literature mentioned above) are fascinating. It may be said, however, that the variety of reaction paths observed makes it difficult to see whether the knowledge gained by these studies can be used for other syntheses. Another tandem synthesis* based on rhodium-carbene complexes, the cyclopropanation-Cope rearrangement sequence 8-68, was extensively investigated by Davies and coworkers (review: Davies, 1993). This sequence leads to cycloheptadienes (8.154), which are useful for the synthesis of important natural products containing densely functionalized seven-membered rings. The sequence 8-68 requires ready access to 3-diazoalk-l-enes (vinyldiazomethanes) as basis for the rhodium* Tandem syntheses are also known as domino or cascade reactions (see Tietze and Beifuss, 1993).

8.7 Transformations Involving Metal Carbenoids

371 (8-67)

O

8.151

(8-68)

8.153

carbene complex 8.153. Davies (Baum et al., 1987; Davies et al., 1990) found diazo transfer to ethene derivatives containing an electron-withdrawing group in the /?position to be effective for the synthesis of yff-diazoethenes. Another method starts from the condensation of lithium diazoacetate with carbonyl compounds, followed by dehydration of the resulting alcohol (Padwa et al., 1990). A related method begins with a sodium-borohydride reduction of diazoacetoacetates, followed by dehydration of the alcohol (Davies et al., 1992b). In some cases, this cyclopropanation-Cope rearrangement sequence leads, however, to mixtures of cycloheptadienes and other compounds (see, e. g., de Meijere et al., 1991). Ring enlargement of benzene and 1-methoxynaphthalene is possible, but it is not interesting for alkylated benzenes because relatively unstable isomers are formed. Methoxybenzene (anisole) only shows substitution at C(4). No ring enlargement was observed (Davies et al., 1992a). The method is, therefore, not generally ap-

372

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

plicable to aromatic compounds (see, however, the original work of Teyssie's group (Anciaux et al., 1980, 1981) and further investigations reviewed by Ye and McKervey (1994, p. 1121). Dzhemilev et al. (1991) conducted an interesting investigation on the yield of cycloheptatriene formed in the reaction of benzene with diazomethane with various catalysts. The yield decreases in the presence of transition metal complexes in the series Rh-C (100%), Rh2(CF3COO)4 (57%), CuCl (39%), CuBr (37%), Rh2(CH3COO)4 (17%), activated charcoal (15%). Toluene, biphenyl, and dimethylbenzenes yield mixtures of the corresponding regioisomeric cycloheptatriene derivatives in 82-98% yield. With naphthalene, cyclopropanation took place in the 1,2-position only (98%). The benzonorcaradiene formed resisted isomerization to benzocycloheptatriene. Methenylation of aromatic hydrocarbons without catalysts was discussed in Section 8.4. Intramolecular reactions of the type of sequence 8-68 are interesting because the stereochemistry of cyclopropanation is controlled by the diene geometry (see examples in the review of Davies, 1993). They are also useful because of the enantioselectivities that can be obtained in these reactions (see Sect. 8.8, Schemes 8-75 to 8-78). Before we close this section, it should be mentioned that rhodium catalysts were added by Godfrey and Ganem (1990) to solutions of 7V-nitroso amides and they observed that the same products were obtained as with diazo compounds. This is, of course, not surprising, as diazo compounds are intermediates in the decomposition of Af-nitroso amides. Yet, it is remarkable that, to the best of our knowledge, this method has not been investigated more frequently. We add an investigation of Chinese chemists to this section, although it is not related to carbenoid reagents that we have discussed above. Zhou et al. (1993) studied reactions of dimethyl diazomalonate and ethyl diazoacetate with carbonyl compounds mediated by diorganyl tellurides and catalytic amounts of cuprous iodide (8-69). Dibutyl telluride (8.155) yields the dimethyl l-arylethene-2,2-dicarboxylate 8.157 with 4-chlorobenzaldehyde in 95% yield at 100 °C. It is assumed that the reaction passes the telluronium ylide 8.156 as intermediate. If so, the process is clearly different from the carbenoid transformations discussed in this section. The originally diazo-substituted C-atom has nucleophilic character in 8.156 and is not electrophilic, as in 8.104.

(H9C4)2Te + N2=C(COOCH3)2 — ^-^ -N2

8.155

(H9C4)2Te+ — -C(COOCH3)2 8.156

(H9C4)TeO +

C = C(COOCH3)2 H

8.157

8.8 Enantioselective Reactions of Carbenoids

373

There are three leading reviews on metal carbenoid transformation, written by Doyle (1986), by Brookhart and Studabaker (1987), and by Maas (1987). They include aspects of synthesis and of mechanism. The more recent reviews in Trost and Fleming's Comprehensive Organic Synthesis were written by Helquist (1991, use of diazoalkanes) and by Davies (1991, diazo carbonyl compounds). The review of Ye and McKervey (1994) on a-diazocarbonyl compounds also contains examples of metal carbenoid transformations. The book of Hegedus (1994) contains representative syntheses of complex organic molecules obtained by transition metal-catalyzed reactions of diazo compounds. The enormously increased activity in the organometallic chemistry of rhodium is reflected in the review of Sharp (1995). For the period 1981-1992, Sharp found 20000 compounds with Rh - C bonds. He considered 2000 references and he gives 1319 formulae of stable rhodium complexes. His review does not include catalysis by transient Rh catalysts!

8.8 Enantioselective Reactions of Carbenoids It is interesting to note that for the assymmetric formation of cyclopropanes of high enantioselectivity, the use of ketocarbenoids with chiral auxiliaries, e.g., diazoacetates as borneol or menthol esters, has been fairly common for a long time. A pioneering discovery was made, however, relatively early by Noyori's group (Nozaki et al., 1966, 1968; see also Noyori, 1990, 1994), which found some enantioselectivity («6% ee = enantiomeric excess) with the chiral copper catalyst 8.158. After additional work by various authors using more selective chiral copper catalysts in the late 1960's and 1970's (review: Aratani, 1985), two very succesful copper catalysts and a useful cobalt complex were found by the groups of Matlin (8.159), Pfaltz (8.160) and Nakamura (8.161). Matlin et al. (1984) reported that the reaction of 2-diazo-5,5-dimethylcyclohexane-l,3-dione (2-diazodimedone) with styrene (8-70) results in the exclusive formation of only one enantiomer of the spirocyclopropane (as shown by NMR). We do not know the reasons that no further work was reported by these or other authors using the catalyst 8.159 except that of Dauben et al. (1990), who found practically no enantioselectivity when using Matlin's catalysis for the intramolecular cyclopropanation of l-diazohept-6-en-2-one. Pfaltz and his coworkers (Fritschi et al., 1986, 1988a, 1988b; Pfaltz, 1989, 1993) used the semicorrin-copper complex 8.160 and the corresponding 2:1 complex 8.162 as a reagent for cyclopropanation of styrene, buta-l,3-diene, 1-methylpenta-2,4-diene, and hept-1-ene (8-71). The yield and the enantiomeric excess found for the two products are shown in Table 8-2. Where does the high enantioselectivity of catalyst 8.160 come from? The efficiency is depicted in Scheme 8-72, proposed by Doyle (1991). The orientation of the bulky (CH3)2COH groups (R) minimizes steric interaction with the carbene ligand, but allows optimum interaction with the approaching double bond of the alkene

374

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates C6H5

8.159

(8-70)

"CO2Fr 8.163

+

R'

A, 8.164

"CO2R'

(8-7D

8.8 Enantioselective Reactions of Carbenoids

375

Table 8-2. Products of cyclopropanations (8-71) with the semicorrin-copper complex 8.160, after Fritschi et al. (1988 b).

R1

R

cfit c6i

1^

CH 2=CH (H3C)2C=CH C5HU

Yield (%) 8.163/8.164

85:;15 82::18 63::37 63::37 82::18

(17?,37?,45)-Menthyl 65-75 (15,35,47?)-Menthyl 60-70 (15,35,47?)-Menthyl 60 (15,35,47?)-Menthyl 77 (15,35,47?)-Menthyl 30

ee (%)

8.163

91 97 97 97 93

(15,25) (15,25) (15,27?) (15,27?) (15,25)

ee (%]I 8.164

90 95 97 97 92

(15,27?) (15,27?) (15,25) (17?,25) (15,27?)

(8-72)

502 S

A'002 ^vV6"5

^xA S S

S\

/fl /R

C66H6

8.165

8.166

R

fl

R

S

H5C6/

8.167

8.168

COZ = benzyloxycarbonyl

(styrene). The four limiting configurations are shown in this front view. Two of them (8.167 and 8.168) are less favorable because R and the phenyl group of styrene are on the same side, as shown in the figure above formulae 8.167 and 8.168. Therefore, monosubstituted alkenes are expected to give higher enantioselectivity than 1,2-disubstituted alkenes. Similar ligands, but on the basis of 4,4',5,5/-tetrahydro-2,2'-methylene bioxazoles (8.169), were developed first by Masamune's group (Lowenthal et al., 1990; Lowenthal and Masamune, 1991), by Evans et al. (1991, 1992) and again by the group of Pfaltz (Miiller et al., 1991). The latter two groups also described ligands of the 4,4/,5,5'-tetrahydrobioxazole (8.170). In addition, Leutenegger et al. (1992) and Nishiyama et al. (1992) developed 5-azasemicorrin ligands (8.171) and analogous aza derivatives of the bioxazole 8.169, respectively. Copper complexes of these three types of ligands also efficiently catalyzed the formation of highly enantiomeric cyclopropanes from alkyl diazoacetates and styrene, hept-1-ene, and other alkenes. All these results show that the enantio- and diastereospecificity are highly dependent on the size of substituents R in 8.169-8.171 and of methyl groups at the methylene C-atom in 8.169 or of phenyl groups in the

376

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

8.169

8.170

8.171

4,4'-positions of 8.169. It is likely that copper(i) is the catalytically active oxidation state. Ito and Katsuki (1994, and preceding papers mentioned in reference 5) demonstrated that the cyclopropanation of styrene with diazoacetates as well as the ring expansion of oxetanes to tetrahydrofurans gives products of high asymmetry (in part >90% ee) if copper complexes of chiral 2,2/-bipyridine derivatives are used as catalysts. The structure of these complexes is similar to that of catalysts like 8.160 and complexes of 8.169. The work of Nakamura (Tatsuno et al., 1974; Nakamura et al., 1978a, 1978b) is not only interesting because he used a cobalt complex (8.161) as cyclopropanation catalyst, but also because of enantiomeric selectivity. The latter was high when using dienes and styrene as substrate (8-73), but low with simple alkenes. /== H5C6

+ +

N2=/

CO22CH22f-C H 44 9 9

8 161 ' > 87%

(8-73)

HgCtf

A

'"CO2CH2?-C4H9

70%

88% ee (1 S,2S)

. A.. H5C£"

"CO2CH2f-C4H9

30%

81 % ee (1 S,2fi)

Nakamura's catalyst was used later by Scholl and Hansen (1986). As cyclopropenyl esters are formed in analogous reactions of metal carbenoids with alkynes, it may be that the final products are furan derivatives, as it is known (Komendantov et al., 1975) that such rearrangements (8-74) take place easily in the presence of copper catalysts. Chiral rhodium(n) catalysts were tested for enantioselectivity in cyclopropanations surprisingly late after the discovery of their general effectiveness in carbenoid reactions. The first investigations were carried out by the group of McKervey (Kennedy

R = CgH5, n - C^g, t-

8.8 Enantioselective Reactions of Carbenoids

377

and McKervey, 1988; Kennedy et al., 1990) and by Brunner et al. (1989). McKervey and coworkers used mandelate and proline derivatives of dirhodium tetraacetate (8.172 and 8.173); Brunner's group tested various enantiomerically pure carboxylic acids R'R"R'"CCOOH with substituents R' to R'" as H, CH3, C6H5, OH, NHCOCH3 and CF3 in dirhodium complexes.

In cyclopropanation of styrene with ethyl diazoacetate, Brunner et al. obtained products for which the ee was less than 12%, and in an intramolecular cyclopropanation McKervey's group also reached only 12%. In applications to aromatic cycloaddition and CH insertion reactions, ee was higher, but still less than 40%. These disappointing results are due to the fact that in chiral dirhodium tetracarboxylates, the centers of chirality are far removed from the carbene center in the metal-carbene adduct. This explanation encouraged Doyle to test dinuclear rhodium complexes with chiral carboxamides. It is known (Bear et al., 1984) that the isomer 8.174, possessing four bridging amide ligands positioned such that each rhodium atom has a pair of nitrogen donor atoms in a c/s-arrangement, is the preferred configuration. Doyle et al. (1990), therefore, synthesized the three chiral dirhodium complexes tetrakis(4-alkyl-2,3,4,5-tetrahydrooxazol-2-ones) 8.175 (IPOX = 2,3,4,5-tetrahydro-4-isopropyloxazol-2-one), 8.176 (BNOX = 4-benzyl-2,3,4,5-tetrahydrooxazol2-one), and 8.177 (MPOX = 2,3,4,5-tetrahydro-4-methyl-5-phenyloxazol-2-one) and tested them in the reaction of D- and L-menthyl diazoacetate with styrene. These complexes block approach by styrene in such a manner that generally ee values for the ds-cyclopropanes are greater than those for the frows-cyclopropanes (cis: 20-63% ee, trans: 4-34% ee for the same combinations). The chirality of the menthyl group also has a significant influence on the enantiomer ratios. Further experiments conducted by Alonso and Fernandez (1989) and others suggest that metal carbenes are stabilized by electron donation through the

R 8.174

378

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates H

Rh2(4S-IPOX)4 8.175

Rh2(4S-BNOX)4

Rh2(4H-MPOX)4

8.176

8.177

dirhodium-ligand framework and from substituents on the carbene. Polar substituents of the carboxamide can orient and stabilize the bound carbene, thereby directing incoming nucleophiles to backside attack on the side of the carbene, opposite of the stabilizing substituent. On this basis, in a joint effort with Martin and Muller (1991 a), Doyle developed a series of dinuclear rhodium 2-pyrrolidone-5-carboxylate complexes that might give better enantiomeric ratios in cyclopropanations (see also Muller and Polleux, 1994). This was indeed the case for a series of intramolecular cyclopropanations of allyl diazoacetates with the complex Rh2((5S)-MEPY)4 obtained with chiral methyl 2-pyrrolidone-5-carboxylate (MEPY = 8.178): an ee between 65 and ^94% was found. Doyle et al. (1993 a) continued that work with additional inter- and intramolecular cyclopropanations as well as with intramolecular CH insertions. Doyle and his coworkers again obtained good-to-excellent enantioselectivity with the same catalyst. Examples are given in Schemes 8-75 to 8-77. In additional papers, Doyle's group reported that the same catalyst also gives very high optical yields in alkyne cyclopropenations and in other CH insertions (Doyle et al., 1991 b; Doyle et al., 1992 b, 1993 c, 1994; Protopopova et al., 1992). Mechanistically most important are the X-ray structures determined for [Rh2((5S)-

H 8.178

(8-75) c/s:

86%(1S,2fl) *

48%

<1 S' 2S>

o-Men = o-Menthyl, (+)-(1S,2fi, 5S)-2-(2'-propyl)-5-methyl-1-cyclohexyl

8.8 Enantioselective Reactions of Carbenoids

98%(1S,5fl)

91%(S)

379

(8-76)

(8-77)

MEPY)4] and another dinuclear rhodium catalyst that showed lower enantioselectivity (Doyle et al., 1993 a). Those structures allowed an understanding of yield and selectivity results on the basis of the effects described above. As mentioned in Section 8.7, rhodium catalysts are very expensive. This is even more the case for chiral Rh catalysts. A practical alternative to their use for asymmetric cyclopropanation was developed by Davies and Cantrell (1991) in the context of Davies' work on 3-diazoalk-l-enes (vinyldiazomethanes). The intramolecular cyclopropanations of these diazo compounds are remarkably c/s-stereoselective in contrast to intermolecular reactions with diazoacetates. Consequently, Davies and Cantrell studied the strategy to use chiral auxiliaries bound to the diazoalkene in order to achieve asymmetric induction. In searching for a suitable auxiliary of relatively low price, (~)(R)-pantolactone (8.179, developed by Helmchen's group; Poll et al., 1985) appeared to be a reasonable choice because it would be incapable of 5-membered ring formation by an intramolecular CH insertion, a common sidereaction in carbenoid chemistry. The corresponding 2-diazo-4-phenylbut-3-enoate 8.180 gave cyclopropanes with styrene in refluxing dichloromethane and at 0 °C on [Rh2(OCOCH3)4] catalysis in 91% and 84 % yield, respectively, of the two cisisomers 8.181 and 8.182 (Scheme 8-78). The major isomer is obtained in 89% ee at reflux and 91% at 0°C; its configuration was (1R,2R). Six other chiral ahydroxy-ester auxiliaries were tested and resulted in useful information on their structural requirements as chiral auxiliaries for this cyclopropanation. Other ligands L for the catalyst were also tested (Davies et al., 1993; Davies and Hutcheson, 1993). Synthetic aspects were discussed in a joint paper with Doyle's group (Doyle et al., 1993 b). The high diastereoselectivity with a-hydroxy esters as auxiliaries indicates that a fairly rigid transition state must be involved. As a plausible explanation, the authors propose that the carbonyl group of the auxiliary interacts with the carbenoid complex 8.183 to generate a dipolar complex 8.184 prior to the cyclopropanation step (8-79). The complex is rigid, as only 5-ring but not 6-ring lactones are effective.

380

8 Dediazoniation Reactions Involving Carbene and Carbenoid Intermediates

(8-78)

8.182

(8-79)

w 8.183

8.184

Davies and coworkers assume, however, that the reaction does not proceed to an uncoordinated ylide, as suggested by Padwa and Krumpe (1992)*. This method of diastereoselective cyclopropanation can also be used with reasonable success for the enantioselective entry to tropanes by a "tandem" cyclopropanation-Cope rearrangement of the 2-diazobut-3-enoate with the (7?)-pantolactone auxiliary group in the presence of 7V-(tert-butoxycarbonyl)pyrrole (8.185). The product 8.186 was obtained by Davies and Huby (1992) with 69% ee. It can be transferred in three steps into 8-azabicyclo[3.2.1]octane-2-carboxylates (8.187), which are the parent compounds for the corresponding 3-aryl derivatives. The latter are valuable probes for studying the neurochemistry of cocain abuse (Carroll et al., 1992; Lewin et al., 1992; Abraham et al., 1992). Another group of medicinally interesting compounds, namely ether analogs (8.188, R = C2H5) of the tetrahydrofuranone antibiotic (-)-acetomycin (8.188, R = COCH3), can also be obtained by the method via 2-diazobut-3-enoates, as Davies and Hu (1993) demonstrated. This section has clearly demonstrated that enantioselective rhodium-carbenoid reactions only developed strongly in recent years, but it seems that today (1995), they are at the frontier of scientific activities on diazo-carbenoid chemistry. There, I see * For further details of the mechanism, see Davies et al. (1993, Scheme III).

8.8 Enantioselective Reactions of Carbenoids BOC

N—BOC

381

O

•K-tr^ ~i

H3C —N^

xCOOCHg

3

8.185

^^

8.186

8.187

a similarity to recent European Championship races on the Rotsee in Switzerland: Rowing crews that are in the middle field for the first 1000 or 1500 meters of the race, may win because they have still enough energy for the last 500 meters and, therefore, they may cross the goal line first! Diazo carbenoid chemistry, however, is not yet on the finishing line, but developments such as the synthesis of polymer-bound soluble rhodium complexes that are recoverable and, therefore, less sensitive to the exceedingly expensive rhodium (Doyle et al., 1992 a) or the use of relatively inexpensive chiral auxiliaries for enantiocontrol (Davies and Cantrell, 1991) are still energy reserves that may be important to win the race! Enantioselective use of aliphatic diazo compounds was reviewed by Doyle in three papers (1991, 1992, 1993), and by Ye and McKervey (1994). Potential industrial applications were summarized in a book edited by Collins et al. (1992). Scientific aspects of asymmetric catalysis in general were discussed in a monograph by the pioneer of the use of chiral catalysts, Noyori (1994). There is no doubt that further progress reports will be necessary in coming years!

9 Miscellaneous Reactions Involving Diazo and Related Compounds

9.1 Electrophilic and Nucleophilic Substitutions at the C(«)-Atom of Diazo Compounds In various chapters, the nucleophilicity of the C(a)-atom of aliphatic diazo compounds has been mentioned. It is, therefore, not surprising that electrophilic reagents will substitute a proton or another electrofugic group in this position, in particular as the C(a)-atom is sp2-hybridized. Accordingly, experience from electrophilic aromatic substitution might be applicable, and aliphatic diazo compounds might have been substituted successfully and often by many electrophilic reagents since the beginning of this century. An overview of the literature tells us that the situation is quite different from that mentioned above, as demonstrated by the following two examples. Classical electrophilic substitutions, like nitration and halogenation, have been accomplished only since the 1960's (see below). The pioneering work of Huisgen and Koch (1954, 1955) on diazoalkanes as coupling components for azo coupling with arenediazonium ions (see Sect. 4.4) is not mentioned in the large chapter on substitution reactions in the monograph of Regitz and Maas in 1986. There are various reasons that may lie behind this development. First, for almost 100 years, electrophilic substitutions were a domain of aromatic chemistry and, at least before Huisgen's review (1955) on the reactivity of diazoalkanes, the large majority of organic chemists did not spend much time on the question that, apparently, there are no similarities between aromatic and aliphatic diazo compounds. Second, it is obvious - even today - that electrophilic substitution reactions of aliphatic diazo compounds are more complex and, therefore, less predictable than the substitution of sp2-hybridized C-atoms in aromatic and aliphatic compounds by arenediazonium ions. Nitration of aliphatic diazo compounds was studied by Schollkopf's group (Schollkopf and Schafer, 1965; Schollkopf et al., 1969). They nitrated ethyl diazoacetate with dinitrogen pentoxide in CC14, at — 30 °C and obtained, besides ethyl diazonitroacetate (9.2, yield 35%), the nitric ester of ethyl glycolate (9.3, 21%). Scheme 9-1 explains the low yield. Stoichiometrically, only half an equivalent of the diazoacetate is nitrated; the other half is the proton acceptor for the deprotonation of the intermediate with a diazonio group (9.1). Schollkopf et al. (1969) tried, therefore, to improve the yield of the diazonitro compound 9.2 by adding good proton acceptors like pyridine or triethylamine, but they Diazo Chemistry II: Aliphatic, Inorganic and Organometattic Compounds. By Heinrich Zoliinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

384

9 Miscellaneous Reactions Involving Diazo and Related Compounds

C —COOC2H5 + N2O5

F-

*-

H—C —COOC2H5

*

v No39.1 C-COOC2H5

H2C— COOC2H5 ~

N

2

(9-1)

+

I

/C— COOC2H5 K,^

+

-

9.2

were not successful. Therefore, we have doubts whether the mechanism is indeed as simple as that shown in Scheme 9-1. tert-Butyl diazoacetate can be nitrated by the same method. On treatment of tertbutyl diazonitroacetate with trifluoroacetic acid in diethyl ether Schollkopf and Markusch (1966, 1971) obtained the parent compound, diazonitromethane in good yield (86%, 9-2). Diazonitromethane is very explosive. 02NX C—COOC(CH3)3

+ F3CCOOH

*-

yCH

NjT

CH3 + 2 CO2 + H2C=C

(9-2) CH3

Diazodinitromethane can be obtained by further treatment of diazonitromethane with N2O5 (Schollkopf and Markusch, 1969, 1971). Schollkopf's method was applied by Regitz et al. (1979 c) to the nitration of a-diazomethylphosphoryl compounds. No detailed reports on halogenations of diazo compounds with molecular chlorine or bromine can be found in the literature. Chloro- and bromodiazomethane are obtained, however, by treatment of CH2N2 with tert-butyl hypochlorite or hypobromite, respectively, at —100 °C in a pentane-chlorotrifluoromethane mixture. These diazohalogenomethanes are very unstable. The bromination and iodination products of diazomethylphosphoryl compounds, which Regitz et al. (1979 c) obtained from the silver derivatives of these diazomethane derivatives with cyanogen bromide (BrCN) and molecular iodine, are somewhat more stable. In contrast to diazomethane, a-diazo-/?-carbonyl and -yff-phosphoryl compounds cannot be halogenated by the direct methods mentioned above, but the corresponding a-mercury-bis(a-diazo-yff-carbonyl) (9.4) or (a-diazo-a-silver-yff-phosphoryl) derivatives (9.6) must be synthesized first. The metallated compounds 9.4 and 9.6 react with molecular bromine and iodine or with other halogenation reagents, like sulfuryl chloride or cyanogen chloride. The compounds 9.5 and 9.7 are obtained in a yield of 30-90% (Schollkopf et al., 1968, for ethyl diazoacetate; Regitz et al., 1979c, for diazophosphoryl compounds).

9.1 Electrophilic and Nucleophilic Substitutions at the C(a)-Atom of Diazo Compounds

385

Schemes 9-3 and 9-4 are sequences of two substitutions, first a metallode-hydrogenation, followed by a halogeno-de-metallation. Scheme 9-3 is analogous to the well known electrophilic aromatic sulfonation of anthraquinone in position 1. This isomer is obtained only if the reaction is run in the presence of catalytic amounts of mercury (n) salts. Nowadays, however, larger effort is devoted to either replace mercury by other catalysts, or in the search for processes leading to (practically) complete recovery of the mercury. This case raises two questions with respect to the reaction sequence (9-3); first, whether it is possible to apply a one-pot process with catalytic amounts of a mercury compound (not necessarily HgO) to the synthesis of compounds 9.5, and second, whether mercury can be completely recycled in processes using either stoichiometric or catalytic amounts of the element. The observation of Schollkopf and coworkers, that the mercury method is applicable to a-diazo-/?-carbonyl compounds, but not to diazomethane, is likely to be due to the same reason as the selective sulfonation of anthraquinone in the 1-position. The mercury ion approaches the reacting CH group via a complex with the O-atom of the neighboring carbonyl group. Mercuration of a-diazo-/?-carbonyl compounds and of anthraquinone are different, however, in another aspect, namely substitution by the metal takes place at the C-atom neighboring the carbonyl group

2

^C-COOC2H5

+

HgO

-^-

N2

S02Q2, Br2, or I2

(9-3)

Hg)<2

X = Cl, Br, or I

gx

9.6 h BrCN or I2

X = Br or I

AgX

R = OCH3 or C6H5

x y

D r

II

o 9.7

Q r\

(9-4)

386

9 Miscellaneous Reactions Involving Diazo and Related Compounds

of diazoacetate, but at the second C-atom from the carbonyl group of anthraquinone. The literature on metallo-de-hydrogenations of aliphatic diazo compounds is, in contrast to that on substitutions with classical electrophilic reagents, fairly large. It includes the monovalent metals Li, Na, and Ag, the divalent metals Mg, Zn, Cd, and Hg, the trivalent metal Tl, and the tetravalent metals Ge, Sn, and Pb. In addition, substitutions with the hetero atoms B, As, Sb, Bi, and Si, as well as metallo-demetallations are reported in the literature. Although the synthesis of diethyl mercury(bisdiazoacetate) (9.4) was performed quite early (Buchner, 1895), the majority of papers on metallation was published in the 1960's and 1970's*. Nowadays, most important for organic syntheses are lithiodiazoalkanes and, to a certain extent, the silver compounds. Both have a relatively high solubility in organic solvents. Lithiodiazomethane is synthesized from diazomethane by lithiode-hydrogenation with phenyl- or butyllithium (Muller and Ludsteck, 1954) or lithium A^-methyl-N-(trimethylsilyl)amide (Scherer and Schmidt, 1965) in ether. The relatively new and important (trimethylsilyl)diazomethane (see Sect. 2.6) can be lithiated also with butyllithium (Colvin and Hamill, 1974; Aoyama et al., 1985 a, 1985 b)**. The metallation of ethyl diazoacetate with butyllithium takes place in ether or in THF-ether even at -110°C (Schollkopf et al., 1974). This result is easily understandable as the C — H bond of diazoacetate is significantly weaker than that in diazomethane. Lithiumdiazoalkanes are highly explosive. Diazocarbonyl and diazophosphoryl compounds react with silver (n) oxide easily (Schollkopf and Rieber, 1969). In diazomethane, both H-atoms are replaced with silver acetate in a mixture of ether and pyridine (Blues et al., 1974). Mono- and disilver diazo compounds are often used for C-alkylation (see examples given by Regitz and Maas, 1986, Sect. 14.6). Derivatives of diazo compounds containing silyl groups are noteworthy. (Trimethylsilyl)diazomethane became a very important substitute for diazomethane, as mentioned several times in this book (e.g., in Sects. 2.6, 7.7, and 10.3). (Trimethylsilyl)diazomethane is obtained by reaction of lithiodiazomethane with chlorotrimethylsilane (Lappert and Lorberth, 1967). The remaining H-atom of the (trimethylsilyl)diazomethane can be replaced by another trimethylsilyl group in the same way (Glotzbach and Lorberth, 1980). An interesting compound is the diazoacetate containing a pentamethyldisilanyl group (9.9). The latter was obtained by Ando et al. (1981 c) in the reaction (9-5) of mercury bis(ethyl diazoacetate) with bis(pentamethyldisilanyl) disulfide (9.8). Organic reagents containing an electrophilic C-atom substitute aliphatic diazo compounds at the C(a)-atom. Summarizing the extensive literature on such reac* Regitz and Maas (1986) give in Sections 14.1 -14.2 and in the Addendum 47 references on metallations of aliphatic diazo compounds, six of which were published in the period 1895-1959, 34 between 1960 and 1979, seven after 1979. The largest number of references is related to mercuration and metallo-de-mercuration, but their importance nowadays is small, due to the environmental problems related to mercury. ** For a recent theoretical investigation of lithiodiazomethane and C-lithiated (trimethylsilyl)diazomethane, including an X-ray crystal structure of the latter, see Boche et al. (1994).

9.1 Electrophilic and Nucleophilic Substitutions at the C(a)-Atom of Diazo Compounds

y

CH3

COOC2H5\

^,

387

COOC2H5

(CH3)3Si —Si —S4-

(9-5)

*• 2 (CH3)3Si —Si-C CH3

CH3

9.8

N2

9.9

tions, one easily recognizes that the large majority of such processes was accomplished with diazoalkanes containing electron-withdrawing substituents at the C(a)-atom, i.e., with diazocarbonyl, -phosphoryl, and some -sulfonyl compounds. In about half of these investigations, a metallated derivative (mainly Li, Hg, or Ag) was used. Only few substitutions with unactivated diazoalkanes, such as diazomethane, are reported. This summary indicates, therefore, that aliphatic diazo compounds are often not sufficiently nucleophilic for such substitutions and that general predictions for applications to other, apparently similar, reactions are not reasonable. A reaction that does work with simple diazoalkanes is the acylation with acid chlorides. This synthesis of diazo ketones was found by Staudinger et al. (1916 b), but its broad applicability and the optimization of the reaction conditions is mainly due to the work of Arndt and Eistert (Arndt et al., 1927; Arndt and Amende, 1928). Eistert proposed mechanism 9-6 for this reaction in 1935 and it was corroborated later in many respects. Mechanism 9-6 explains that the second equivalent of diazomethane is necessary to remove one of the CH2-protons before dediazoniation and, therefore, to prevent the formation of the (chloromethyl)alkyl ketone 9.10. Scott and Minton (1977, and references given there) showed that in some cases triethylamine and other amines also can be used as proton acceptors. Their method is the basis of two Organic Syntheses procedures, i. e. , l-diazo-2-phenylethan-2-one from benzoyl chloride (Bridson and Hooz, 1988) and l-diazo-4-phenylbutan-2-one from 3-phenylpropionyl chloride (Scott and Sumpter, 1993)*. When working on the acylation of diazomethane, Arndt and Eistert (1935) found the method for homologization of carboxylic acids in which acylation of the diazo ketone with the acid chloride is followed by a Wolff rearrangement (see discussion in Sect. 8.6). n **/P R— C + CH2— N2+ N

°" I R— C — CH2— N2+

^

ci

R

"

"

(9-6)

"

o>-CH^,

9 10

-

See also Regitz and Maas, 1986, Tables 14.8 and 14.9.

+ CH3CI + N2

388

9 Miscellaneous Reactions Involving Diazo and Related Compounds

When diazoacetates are used as substrates, the reaction with acyl chlorides leads to diazo-a,a'-dicarbonyl compounds, e.g., with acetyl chloride to ethyl 2-diazo3-oxobutanoate (9-7)*. ^O H3c-C(

COOC2H5 + HC -

Cl

H3C -

COOC2H5 C-C

O

N2

(9-7)

N2

Pettit and Nelson (1986) have designed an apparatus for diazo ketone preparation in which the carboxylic acid is first treated with oxalyl chloride dissolved in ether in one compartment. The acid chloride is formed after addition of triethylamine and a catalytic amount of dimethylformamide. Then the solution is filtered and added to ethereal diazomethane at - 78 °C in the second compartment. Another useful electrophilic reagent for additions to diazo compounds is bis(trichloromethyl) carbonate (CO(OCC13)2; "triphosgene")** As shown by Padwa's group (Marino et al., 1994; Brown et al., 1994), it allows synthesis of ethyl 2-diazomalonyl chloride (H5C2OCO - CN2 - COC1) with ethyl diazoacetate. Ethyl 2-diazomalonyl chloride can be used for the preparation of a-diazoamides (see Sect. 8.7, Schemes 8-59 and 8-66). It is interesting that systematic investigations on reactions of aliphatic diazo compounds with simple aldehydes and ketones were conducted relatively late, namely in the early 1970's. Schollkopf and Frasnelli (1970) demonstrated that, using metallated diazocarbonyl compounds, aldehydes form aldols in excellent yields (>90%), as shown in (9-8) for the example of benzaldehyde. Later, Schollkopf et al. (1974) showed that the metallation step is not necessary when organometallic bases, such as butyllithium are present in the aprotic, nonpolar system (e. g. , in ether -THF-hexane). The method can be generalized for many aldehydes and ketones, even with KOH as base (Schollkopf and Scholz, 1976). H H5C6-C 0

COOC2H5 + HC "*

^

j COOC2H5 H5C6-C-C in

0-8)

N

*

A slightly more complex case was investigated at about the same time by Woolsey and Khalil (1972), namely the reaction of l-diazo-3-phenylpropan-2-one with benzaldehyde (9-9). It is more complex because one might expect a reaction of the aldehyde with the CH2 group of the diazo ketone, and secondly, the reaction was run in ethanol with NaOH as base and not in the system used originally by Schollkopf and his coworkers. The product was, however, 2-diazo-l-hydroxy-l,4-diphenylbutan-3-one, as expected for an aldol-type substitution. * For additional examples, see Regitz and Maas (1986, Table 14.10). ** "Triphosgene" is a typical example of a trivial name that should be eliminated from the literature because it is not at all related to the structure of the compound, but only to its origin.

9.1 Electrophilic and Nucleophilic Substitutions at the C(a)-Atom of Diazo Compounds

H H5C6-C

H |

CH2-C6H5 +

N2=CH-C

-

-

389

/C-CH2C6H5

H5C6-C-C

X

(9-9)

N

These results drew attention to a reaction studied by Biltz and Kramer in 1924, the general applicability of which, however, was not recognized for 50 years ! These authors studied the reaction of ethyl diazoacetate with the tetrahydrate of pyrimidine2,4,5,6-tetrone (9.11, alloxane) and found the addition product 9.12 (9-10). N2 HO

II C— COOC2H5

yCOOC2H5

HC

HN

NH 0

9.11

HN

NH O 9.12

Regitz and Maas (1986, Table 14.5) give 23 further examples of diazomethyl alkylation with aldehydes and ketones. A potential difficulty may be the dimerization of diazocarbonyl and related compounds in the presence of alkali hydroxides, by which l,4-dihydro-l,2,4,5-tetrazines are formed (see the discussion in Sect. 9.2). We know, however, of only one case in which this reaction interfered (Disterdorf and Regitz, 1976; diazomethyl(diphenyl)phosphine oxide, (H5C6)2P(O)-CH = N2). In the context of ring enlargements by the Tiffeneau rearrangement, we have already mentioned in Section 7.7 the ring enlargement of cyclic ketones by reaction with diazomethane (see Scheme 7-48). This process is, of course, also an electrophilic substitution at the C(a)-atom of a diazoalkane. Two ring enlargements of this type are described in Organic Syntheses, namely the formation of cycloheptanone from cyclohexanone (33-36% yield) by de Boer and Bakker (1963) and of 2-phenylcycloheptanone from cyclohexanone and phenyldiazomethane (41-46% yield) by Gutsche and Johnson (1963). Substantial improvements in yields and selectivities of ring expansions of type 7-48 are possible by using (trimethylsilyl)diazomethane [(CH3)3SiCHN2] instead of diazomethane, as shown by the work of the group of Aoyama and Shioiri (Hashimoto et al., 1980, 1982; Mori et al., 1982). An example (9-11) is the ring expansion of 2-methylcyclohexanone to 2-methylcycloheptanone (9.13). (Trimethylsilyl)diazomethane gives predominantly 9.13 (69%). With diazomethane the major product is the epoxy derivative 9.15 (26%)*. 2-Methylcycloheptanone (9.13) is formed in low yield (10%, but together with its 3-methyl isomer 9.14 7%). The higher regioselectivity of the reaction with (trimethylsilyl)diazomethane is likely to be due to the bulky silyl group. * For a very recent report on a stereoselective formation of an epoxide, see Bravo et al. (1994).

390

9 Miscellaneous Reactions Involving Diazo and Related Compounds

RCHN2

(9-11)

9.13

9.14

9.15

(Trimethylsilyl)diazomethane was also applied successfully to the total synthesis of pinguisane-type sesquiterpenes for the ring expansion (9-12) of the bicyclooctenone 9.16 by Uyehara et al. (1986). The same authors used (trimethylsilyl)diazomethane for the ring expansion of the bicyclic ketone 9.17 (9-13) in studies on the synthesis of the novel sesquiterpenoid (±) nakafuran-8, a bicyclo [4.2.2] decadiene with antifeedant properties (Uyehara et al., 1992).

. .F,0,C,H.,. 2. K2C03/CH3OH

9.16

(CH3)3Si-CHN2

+

/f,/

-

L^ff

9.17

0-13)

85%

Alkyl halides that show a DN + AN mechanism (Ingold terminology: SN1) in nucleophilic aliphatic substitutions can be used as electrophilic reagents in C-alkylations of diazoalkanes. An example is the synthesis of ethyl 2-diazopent-4-enoate (9.18) by reaction of ethyl silver diazoacetate with 3-iodoprop-l-ene (allyl bromide) (9-14, 66%; Schollkopf and Rieber, 1969). Cyclopropenylium ions (e. g. , 9.19) are known to be electrophilic. Eisenbarth and Regitz (1982) synthesized tert-butyl tri(te/t-butyl)cyclopropen-3-yl diazoacetate (9.20)

= CH— CH2I

/COOC2H5 + AgCx N N2

COOC2H5 -

^

H2C=CH— CH2— C

(9-14)

X

N2

9.18

9.1 Electrophilic and Nucleophilic Substitutions at the C(a)-Atom of Diazo Compounds

391

from tert-butyl mercury-bis(diazoacetate) and tri-te/t-butylcyclopropenylium tetrafluoroborate. In a thermally induced ring enlargement via the pyridazine derivative and azo-extrusion (9-15), l,2,3,4-tetra(tert-butyl)cyclobutadiene (9.21) is obtained (Eisenbarth and Regitz, 1982; see also Masamune et al., 1973).

R

+

Hg

9-19

R = '-c4H9

I _ (9-15)

9.21

Heteroaromatic cyclic cations like pyrylium and thiopyrylium ions (9.22, X = O or S, respectively; R = H or alkyl) react with diazocarbonyl and diazophosphoryl compounds in the 2-, 4- and 6-positions if these are not substituted (R = H). Triethylamine is necessary for removal of the proton in one of these positions, to form the 4//-pyran or -thiopyran (9.23; 9-16), as found by the group of Regitz (Regitz and Khbeis, 1984; Regitz et al., 1985).

N

2

BF49.22

X = O, S Y = COOAlk, POAIk2 R = see text

|

(9-16)

392

9 Miscellaneous Reactions Involving Diazo and Related Compounds

Basically, an analogous situation is found with imidazolium, thiazolium, and their benzo-annelated derivatives (9.24), although byproducts may interfere with a straightforward addition to diazo compounds (see Regitz et al, 1985). ^__H /

X = N-Alk, N-Ar, S, O Y = N-Alk, N-Ar

9.24

Two recent investigations of the groups of Olah and Adam led to impressive examples of diazoalkane reactions with unconventional electrophilic reagents. Olah et al. (1992) studied the reaction of triphenylcarbenium tetrafluoroborate (10 mmol) with diphenyldiazomethane in dry dichloromethane hoping to detect the 1,1,2,2,2-pentaphenylethyl cation (9.25). The reaction yielded, however, tetraphenylethene (79%) and a small amount (< 0.2%) pentaphenylethane. Using perdeuterated triphenylcarbenium salt or 13C-enriched diphenyldiazomethane, the authors demonstrate, by analysis of the labeled products, that the results are consistent with the mechanism (9-17), i.e., with the 1,1,2,2,2-pentaphenylethyl cation as steady-state intermediate, which is expected to undergo 1,2-phenyl migration via a phenonium ion and subsequent phenyl group scrambling. 3,4-Tetrasubstituted-l,2-dioxetanes (9.26) are electrophilic reagents that form stable adducts with nucleophiles, e.g., with carbanions (Adam and Heil, 1992). Adam and Treiber (1994) demonstrated that the sterically less hindered oxygen atom of these dioxetanes add at the C(a)- and at the N(/?)-atom of diazoalkane to form the O,N-dipole (9.27) and the O,C-dipole (9.29), respectively. Dediazoniation and cyclization of 9.27 leads to 1,3-dioxolanes (9.28) and that of 9.29 to fragmentation, i.e., to the ketones 9.30 and 9.31 (9-18). After the numerous reactions with electrophiles, it is remarkable that it was only in 1994, that Weiss et al. found a nucleophilic reaction at the C(a)-atom of a diazo compound with preservation of the diazo function. These authors synthesized the a-(aryliodonio)diazo compounds 9.32 and 9.33 by reaction of bis(pyridinioiodo)benzene bis(trifluoromethylsulfonate) with ethyl and tert-butyl diazoacetate, respectively (9-19)*. The structure 9.33 was corroborated by an X-ray structure analysis. These novel substituted diazoacetates are characterized by an "Umpolung" (see Seebach, 1969, 1979; Seebach and Enders, 1975; Hase, 1987) of the reactivity of the C(a)-atom. It allows substitution of 9.32 with a series of neutral nucleophiles at room temperature to give new a-substituted diazoacetates (9.34) (9-20).

For another way to synthesize 9.32 and 9.33, see Weiss et al. (1994).

9.1 Electrophilic and Nucleophilic Substitutions at the C(a)-Atom of Diazo Compounds

9.25

393

394

9 Miscellaneous Reactions Involving Diazo and Related Compounds O—O

R

(9-18) 9.29

R4\ R5

O

1

R^^R1

R1

R2

9.30

+

1 2/

R ^

9.31

9.28

'\xwi1 ——

T O

^ \

•/—'

9.32:R = C2H5 . R = {_c

9 33

OR

n"

<9"19)

9.2 The N(p)-Electrophilicity

of Aliphatic Diazo Compounds

395

N2

9 32 + Nu

N + U^°" C

-

(9 20)

-

Nu+ = —

—S(CH3)2 —As(C6H5)3 —Sb(C6H5)3 —N(C2H5)3

9.2 The N(/?)-Electrophilicity of Aliphatic Diazo Compounds The electrophilicity of aromatic diazo compounds is well known and is extensively documented by the azo coupling reaction, one of the classical electrophilic aromatic substitutions (see Zollinger, 1994, Chapt. 12). Aliphatic diazo compounds, however, are considered by most chemists as being unable to react as electrophiles in azo coupling reactions. This assumption is incorrect. The reactivity as electrophiles of a series of substituted diazoalkanes lies in between that of arenediazonium ions and that of diazoalkanes. Alkanediazonium ions are highly reactive N(/?)-electrophilic compounds, but azo coupling reactions are generally slower than the (competitive) dediazoniation (see Sect. 6.1). The 1,2- and 1,4-quinone diazides (e.g., 9.35) are closely related to arenediazonium ions, as shown by the mesomeric structure 9.35 b. They are used on a large scale in industrial azo coupling reactions (see Zollinger, 1991, p. 149 ff.), but their reaction rates are slower than those of arenediazonium ions.

9.35a

9.35b

The mesomeric structure 9.35 a is related to cyclic diazo ketones; based on this structure, 1,2-benzoquinone diazide may be called 2-diazocyclohexa-3,5-dien-l-one

396

9 Miscellaneous Reactions Involving Diazo and Related Compounds

(9.35 a). The compound without the two C = C bonds is 2-diazocyclohexan-l-one. As far as we know, no azo coupling reaction has been reported thereof. The loss of aromaticity in going from the quinone diazide 9.35 to 2-diazocyclohexan-l-one is compensated in heterocyclic diazo ketones (e. g. 2.154, p. 61) by electron-withdrawing groups. The most representative case of an electrophilic reaction of an aliphatic diazo group was found, however, more than one hundred years ago, but relatively few chemists of our time know it! Curtius, the discoverer of ethyl diazoacetate, studied in 1884, 1888b and later (Curtius et al., 1906-1908) the reaction of that compound with aqueous and ethanolic alkali hydroxide. In dilute alkali hydroxide the ester was hydrolyzed, as expected. In concentrated solution, however, in addition to hydrolysis, a "dimerization" product was observed. Curtius elucidated its structure as l//,4/f-l,2,4,5-tetrazine-3,6-dicarboxylate dianion (9.36)*. Hantzsch, the great pioneer in aromatic diazo chemistry, became interested in that really novel reaction and corroborated the experimental work and the conclusions of Curtius (Hantzsch and Silberrad, 1900; Hantzsch and Lehmann, 1900) — but, subsequently, there was complete silence on this reaction for almost half a century!

cocr N NH

cocr 9.36

It was Huisgen, in his classical review (1955, p. 455), who stated that the two molecules of ethyl diazoacetate had different functions in that dimerization. One of them is a C-nucleophile, analogous to the many cases that we have already discussed in Section 9.1; the other, however, is an 7V-electrophile, as given in the mesomeric structure 9.37 b. It reacts like an arenediazonium ion in an azo coupling reaction, analogous to the azo coupling of diazoalkanes, which Huisgen and Koch reported shortly before publication of the review of 1955 (see Sect. 4.4). The first azo coupling reaction is followed by a second, which is an intramolecular azo coupling. Scheme 9-21 depicts the formation of l//,4//-l,2,4,5-tetrazine-3,6-dicarboxylate in a slightly different way, as established by Huisgen in 1955, assuming first that the ester groups are hydrolyzed before the azo coupling, an assumption supported by observations reported previously by Curtius**. * Much later (Chae, 1965; Neugebauer et al., 1983), it became clear that the 1,4-dihydro compound is the most stable isomer. ** There are a number of open questions in (9-21), e.g., whether the 7V-electrophile is indeed the anion 9.37, or if the alkyl diazoacetate reacts as an electrophilic reagent before the ester hydrolysis. Another open problem is the question whether diazoalkanes lacking an electron-withdrawing group also form l/f,4//-l,2,5,6-tetrazines. We found neither positive evidence nor a negative statement for such possibilities. Yet, it might be worth investigating this question, e. g., with a 1:1 mixture of diazomethane and lithiodiazomethane.

9.2 The N(j3)-Electrophilicity of Aliphatic Diazo Compounds

397

=N=CH—COOR + OH~ V -ROH

N=N=CH—COCT

9.37a N=N—CH—COO~ /

9.37b

•QOC—

(9-21)

>

N=N

-ooc-c'

COCT

'

2H+

H

^C— COCT

~OOC— Cv

H

9.36

After Huisgen's explanatory review, there was still silence on this reaction in the scientific community for some years until it was realized by Carboni and Lindsey (1962) that substituted 1,2,4,5-tetrazines are very reactive towards simple alkenes. Sauer et al. (1965), working in the same department as Huisgen at the University of Munich, evaluated such reactions in more detail, including alkynes in addition to alkenes. In the 1970's, dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate (9.38) became much in demand as a synthon. It is obtained easily by esterification of 9.36, followed by treatment with nitrous gases* (9-22; Organic Syntheses, Roger et al., 1992). As the development from the first report of Curtius (1884), one year after the discovery of diazoacetate, to the present widespread use of 1,2,4,5-tetrazines in This dehydrogenation method was discovered by Curtius and Lang (1888).

398

9 Miscellaneous Reactions Involving Diazo and Related Compounds COOCH3

9.36

V

T

^=^

J

0-22)

^T COOCH3 9.38

heterocyclic chemistry is interesting for the history and philosophy of scientific discoveries, we will spend a page on the present state of their applications in the synthesis of heterocycles. Dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate was recognized as an electron-deficient compound that is suitable for Diels-Alder reactions by azo-extrusion with electron-rich, unactivated, and electron-deficient dienophiles (Boger, 1983, 1986; Boger et al., 1992). Diazines can be synthesized by these processes under azo-extrusion. The diazines give pyrroles easily. An example is the synthesis of dimethyl 4,5-dihydro4-phenyl-l ,2-diazine-3,6-dicarboxylate (9.40) with l-phenyl-l-(trimethyIsilyloxy)ethene (9.39) as dienophile (9-23, 90-96%). By ring contraction with zinc dust in glacial acetic acid, dimethyl 3-phenylpyrrole-2,5-dicarboxylate (9.41) is obtained in 52% yield. Instead of 9.39, the corresponding styrene with an a-morpholino group can also be used (87%), but the compound with an a-pyrrolidino group yields only traces of the diazine 9.40 (Boger et al., 1984; also described in an Organic Syntheses contribution of Boger et al., 1992). C = N Heterodienophiles can also be used for the reaction with the tetrazine 9.38. An example is shown in Scheme 9-24, in which the 1,2,4-triazine (9.42) is the product (yield 68%, Boger et al., 1992). Two additional reactions of the tetrazine 9.38 illustrate the wide scope of application in heterocyclic syntheses: N

H5c6 /UCOOR OSi(CH3)3

(CH3)3Si<

COOR R = CH3> C2H5

9.39

:OOR - HOSi(CH3)3

9.41

(CH3)3Si<

\-r\ N1

9.2 The N(/3)-Electrophilicity of Aliphatic Diazo Compounds

399

COOCH3 9.38

+

^T

X"'"

^T

>^N

(9-24)

Cycloaddition of 7V-sulfinylaniline derivatives (9.43) with 9.38 yields dimethyl l-phenyl-4//-l,2,4-triazole-2,5-dicarboxylates (9.44) in methanol (2 d at 80 °C; 9-25; Seitz and Krampchen, 1977). Nair (1975) and Anderson and Hassner (1974) reported on the reaction of 1-azirines (9.45) with tetrazines (R = COOCH3, and Ar (9-26)). The primary product from the cycloaddition is probably the triazepine 9.46, which is not stable, but rearranges by one and two 1,5-hydrogen shifts to 9.47 and 9.48, respectively. These rearrange further to afford pyrimidines (9.49) or pyrazoles (9.50), or both. Reactions 9-25 and 9-26 have now been known for about twenty years. We mention them here in the hope that this will encourage readers to corroborate the structure of the assumed intermediates by direct experimental or theoretical evidence. Roger's reviews (1983, 1986; Boger et al., 1992) contain many more examples, including numerous natural products. COOCH3

\V-

N

N=S=0

+

I

N

II

9.43

R = H, CH3, C2H5

400

9 Miscellaneous Reactions Involving Diazo and Related Compounds

(9-26)

R

R' R = Ar, COOCH3 R7 = H, C6H5

9.50

9.3 Electron Transfer to and from Diazo Compounds: Ion Radicals There are several aspects of electron transfer reactions to and from diazo compounds: First, the processes in an electrochemical cell, in particular those taking place at the surfaces of the cathode and the anode; second, the structure of the intermediates and final products obtained in electrochemical processes; third, reactions of diazo compounds carried out with inorganic and organic reduction or oxidation reagents. The two types of investigations mentioned first are clearly within the domain of physical chemists and the last is a subject in which synthetic organic chemists are interested. It is, however, surprising that joint investigations covering two or all three aspects are relatively rare. We will discuss the investigations that are based on electrochemical techniques, including their mechanisms and products (as far as they are reliably known), in this section and concentrate in Section 9.4 on reactions without that technique but using

9.3 Electron Transfer to and from Diazo Compounds: Ion Radicals

401

old and new reduction and oxidation reagents or, stated in more general terms, electron-donor and electron-acceptor compounds. It is appropriate to start the discussion on electron-transfer processes to and from diazo compounds with polarographic results on electron additions to a-diazo ketones. For such a reaction one expects the formation of a diazo anion radical, in which the negative charge is localized mainly on the O-atom and to give diazenyl radical character to the diazo group (9.51).

9.51

In aqueous buffer solutions (pH 6), Bailes and Leveson (1970) observed, however, three polarographic waves in the reduction of 2-diazo-l-phenylethan-l-one (9.52). They correspond to the transfer of six, two, and two electrons, respectively, a result corroborated by controlled-potential coulometry by the same authors. These three waves are consistent with the mechanism (9-27), i. e., formation of a-aminoacetophenone (9.53), acetophenone (9.54), and 1-phenylethanol (9.55). Furthermore, polarography starting with the intermediates 9.53 and 9.54 gave results consistent with the waves for parts B and C of mechanism (9-27).

XCHN2

+6

y6H+

H5C6-C

* O

/CHNH2 5 6

A

9.52

O

9.53 + 2e + 2H+ 8

HP PH •< « H 5C6—CH

+ 2e + 2H+

"

'

(9-27)

-Nl 3 -NH

,CH3

HP r H5C6—C

OH

9.55

9.54

As a diazo chemist, one is surprised that no dediazoniation is involved. Cleavage of the NN bond in part A of (9-27) is, however, well documented for hydrazone groups in the a-position to a carbonyl function (Cardinali et al., 1973). It is likely that part A consists, therefore, of three two-electron transfers, forming first the hydrazone, then the imine, and finally the amine 9.53. Ethyl diazophenylacetate is reduced to phenylacetate in aqueous dioxane at pH 7 (Jugelt et al., 1972). The authors reported that dinitrogen is formed, clearly indicating that the mechanism of this reduction is different from that of 2-diazol-phenylethan-l-one. Under aprotic conditions (sulfolane), ethyl diazoacetate, but

402

9 Miscellaneous Reactions Involving Diazo and Related Compounds

not diazomethane *, is reduced easily to ethyl acetate with formation of dinitrogen (Elofson et al., 1974). With diazodiphenylmethane, however, Elofson's group found a complex mixture of diphenylmethane (20%), diphenylaminomethane (20%), and small amounts of l,2-bis(diphenylmethyl)diazene (9-28). The diversity of products in the reduction of ethyl diazoacetate, ethyl diazophenylacetate, and diazodiphenylmethane, as well as the lack of reactivity of diazomethane, can hardly be rationalized. (C6H5)2CN2

(9-28) (C6H5)2CH2 + (C6H5)2CHNH2 +

(H5C6)2CHN=NCH(C6H5)2

In the early 1980's, Bethell and Parker (1981, 1982) started to study electrochemical kinetics of one-electron transfer to or from diazodiphenylmethane and of 9-diazofluorene (Parker and Bethell, 1981). These classical and widely investigated diazoalkanes also showed, however, relatively complex effects (see below), which were (correctly) considered not to be representative for the formation mechanism of diazoalkene anion radicals. This is indeed the case for 2-diazo-l,2-diphenylethan-l-one (9.56). Bethell et al. (1984), Hawley's group (1985), and Bethell and Parker (1986a) studied the electrontransfer kinetics to 9.56 and to diethyl diazomalonate in acetonitrile and, partly, in dimethylformamide. Linear-sweep voltammetry studies demonstrated that the anion radical formed at the electrode decomposes by a first-order mechanism (for 9-diazofluorene, however, Parker and Bethell, 1981, found second-order kinetics) and, when using deuterated acetonitrile (CD3CN) as solvent, a negligibly small deuterium kinetic isotope effect was determined. Yet, in the anion-radical formation of diazodiphenylmethane, a large isotope effect was observed by Bethell and Parker (1981, 1982): ArcH3CN/£cD3CN«30, at 8°C. The magnitude of this effect is indicative of tunneling, but it rules out proton or hydrogen atom transfer from the solvent as the rate-determining part of the reaction**. As the observed rates are not extremely fast, it is likely that only the electron transfer takes place at the electrode surface and that the consecutive steps take place in solution (see Jones, 1981). On this basis, the mechanism 9-29 was proposed by Bethell and Parker***. The kinetics of the formation of diazo and carbene cation radicals were also studied by Parker, Bethell and coworkers (Parker and Bethell, 1987; Bakke et al., 1987)****. They used diazodiphenylmethane and its 2,2'-bridged derivatives 9.58 and 9.59. In * For an oxidative electrochemical reaction of diazomethane, see later in this section. ** In the presence of hydroxylic compounds and other proton donors, these reactions are more complex; see Bethell and Parker (1986) for a mechanism involving a complex of a hydrogen-bonded water molecule to the diazo anion radical 9.57. *** It seems to us that this dediazoniation is indeed slower than those of aromatic diazenyl radicals (see Zollinger, 1994, Sect. 8.6, p. 189 ff.). **** por Eg£ spectra of radical cations formed by one-electron oxidation of two diaryldiazomethanes and of 1-phenyldiazoethane, see Ishiguro et al. (1987).

9.3 Electron Transfer to and from Diazo Compounds: Ion Radicals M2

"Ov

"

403

N2*

H5C6

C6H5

9.56 fast

HX fast

_X

(9-29)

H

H5C6

v<

H5C6

C6H5

the presence of pyridine bases, the proton-catalyzed chain reactions of these diazo compounds can be inhibited and, therefore, methanol can also be used as solvent in addition to acetonitrile.

Under these conditions, the primary reactions after the formation of the diazoalkane cation radical can be studied. First-order kinetics were found. The rates are independent of pyridine and methanol and there is practically no deuterium isotope effect in tetradeuterated methanol. The solvent isotope effect (CD3CN and CD3OD and its mixtures) is minimal (e.g., ^CH3OH/^CD3OD = 1-02). These results indicate a simple unimolecular dissociation of the CN bond, forming the dinitrogen molecule and the carbene cation radical. Although we gave only a brief summary of some electrode kinetic investigations, they demonstrate that rate-limiting dediazoniation is likely to be often, but not always, the first step after electron transfer at the electrode. The frequently used method of drawing conclusions from products in order to explain the mechanism after the rate-limiting step has limited validity, however, for reactions involving diazoalkane ion radicals and the corresponding carbene ion radicals because there is often a variety of quite different products formed. Bethell and Parker (1988) classified the reactions of diazo anion radicals and their corresponding carbene anion radicals as well as the reactions of the cation radicals. For the anion radicals intermediates and final products were identified. They correspond at least to four reaction types, namely a) dimerization of the diazo anion

404

9 Miscellaneous Reactions Involving Diazo and Related Compounds

radical before dediazoniation, b) reaction with the (intact) diazoalkane, leading to a chain reaction, c) hydrogen abstraction from the solvent, d) protonation by (relatively) good proton donors such as diethyl malonate and 2,2,2-trifluoroethanol. The difficulties in such an evaluation are very well exemplified by the reduction of 9-diazofluorene (Parker and Bell, 1981; Herbrandson et al, 1983; Bethell and Parker, 1986b). The main final product is l,2-bis(fluoren-ylidenamino)diazene (9.62). Voltammetry at ambient- and low temperature showed that the tetrazine dianion 9.60 is detectable at all temperatures, but that a second intermediate with the tentatively assigned structure 9.61 is also present below — 25 °C (9-30). Both these dimers yield fluorenone azine in two steps (and ring opening of 9.61).

(9-30)

9.61

In most cases in which dimerization is not dominant, proton transfer to the diazo anion radical is the reaction responsible for the majority of final products. These pathways were studied in detail with diphenyldiazomethane in aprotic solvents without added protic compounds (Bethell and Parker, 1981, 1982; Van Galen et al., 1984). Benzophenone hydrazone and diphenylmethane were the major products in this case (9-31)*. * For the multiple pathway leading to these products, see the papers mentioned, and Bethell and Parker (1988), Scheme II.

9.3 Electron Transfer to and from Diazo Compounds: Ion Radicals (C6H5)2CN2

»

> (C6H5)2CH2 + (C6H5)2C = NNH2

405 (9-31)

These products demonstrate that C- and 7V-protonation of the diazo anion radical are feasible. Therefore, there is a certain similarity to the nucleophilic character of these atoms in diazoalkanes. We agree, however, with the statement in the review of Bethell and Parker (1988): "Further investigation of the relationship between charge distribution in RR'CN2~ and protonation is clearly necessary". Bethell et al. (1989 a, 1989 b) studied the kinetics and products of the decomposition of three bis(diazo)indenofluorenes, e.g., ll,12-bis(diazo)-ll,12-dihydroindeno[2.1-#]fluorene (9.63). They found electrochemically-induced chain processes in dimethylformamide solution leading to formation of polyazines.

9.63

Reaction products of carbene cation radicals formed from diazodiphenylmethane were investigated by Pragst and Jugelt (1970). Later, Parker and Bethell (1987) studied the products of diazodiphenylmethane and the two related compounds 9.58 and 9.59, which we discussed above in the context of kinetics. The major products are given in Table 9-1. Table 9-1. Major products (%) of constant current electrooxidation of diazodiphenylmethane (DDM) and its derivatives 9.58 and 9.59 in methanol at 60°C (after Parker and Bethell, 1987). Products

DDM

Ar2CHOCH3 Ar2C=O Ar2C(OCH3)2

32.2 53.6 a

)

9.58

9.59

3.2

56.6

24.5 61.4

30.4

7.1

a

) Not detected.

The very different results for the three diazoalkanes indicate that, under constant current electrolysis, the oxidations take place by competing one- and two-electron transfer pathways. The first steps are shown in Scheme 9-32. The carbene cation radical (9.64) shows the behavior of a radical, abstracting a hydrogen atom from the solvent, and of an electrophile, which reacts at the (nucleophilic) O-atom of methanol. The carbocation 9.65 reacts in the next step in a heterolytic addition to form Ar2CHOCH3, whereas the a-methoxy radical 9.66 gives the corresponding cation by a second one-electron oxidation step to form Ar2C(OCH3)2. It is more

406

9 Miscellaneous Reactions Involving Diazo and Related Compounds ^^^r

Ar2C'+ + CH3OH 9.64

Ar2C—H

+ *CH2OH

9.65 ^^*-

(9.32) +

Ar2C—OCH3 + H 9.66

difficult to understand how diphenylketone is formed. The authors did not investigate that question further, but tentatively consider a pathway via an amethoxy-diaryl carbocation and a nucleophilic displacement as plausible (see their equation 6). The yield ratios of the three diazoalkanes are quite different and can hardly be rationalized. The complexity of product formation by electron transfer from the diazo compound to the electrode is also evident in preparative electrochemical oxidations of diazoalkanes (see review by Fry, 1978). We have already mentioned the investigation of Elofson et al. (1974) in sulfolane because electron transfer to diazomethane did not occur. Yet, electrochemical oxidation in the presence of pyridine was successful and yielded 7V-methylpyridinium perchlorate. The mechanism suggested by Elofson has been questioned by Fry (1978, p. 496). The redox potentials of one-electron oxidation and reduction of aliphatic diazo compounds are relatively small. A table published by Bethell and Parker (1988, p. 400) contains seven corrected oxidation potentials including those of diazomethane, ethyl diazoacetate, diazodiphenylmethane, 9-diazofluorene, and of compounds 9.56 and 9.59. They were obtained by various authors using a rotating platinum disk electrode in acetonitrile and cover the range E1/2(ox) 0.77-2.10 V. The reduction potentials E1/2(red) —1.12 to —1.71 V for four compounds (diethyl diazomalonate, diazodiphenylmethane, 9.56 and 9-diazofluorene) are not strictly comparable because the measurement conditions (cyclic voltammetry) were not exactly the same. Theoretical studies on the structure of the carbene cation and anion radical of the parent species (H2C*+ , and H2C! ~, respectively) performed by MINDO/3, SCF/CI and ab initio (4-13 G) calculations led to the conclusion that the structures H2C:(2A!) and H2C:(2Ei) are similar to those of the neutral carbene in its lowest singlet (*A!) and triplet (3BO state, respectively, if one compares CH bond lengths and HCH angles (see summary of Bethell and Parker, 1988; for neutral carbenes, see also Sect. 8.1 of this book). Removal of an electron from the neutral carbene is energetically much more expensive than addition of an electron. This theoretical result corresponds to conclusions that can be drawn from experimental experience concerning reaction products. They demonstrate that carbene cation radicals are very electrophilic. In this section, we discussed radicals generated by one-electron transfer to or from diazo compounds, i. e., redox reactions. We will add here a reaction of diazo compounds with stable organic n cation radicals, although this process is neither a reduction nor an oxidation. In the 1960's Ledwith found the [2 + 1] alkene cyclodimerization (review: Ledwith, 1972), which is based on the generation of small concentrations of chain-carrying cation radicals from n donor molecules, such as electron-rich alkenes, conjugated

9.3 Electron Transfer to and from Diazo Compounds: Ion Radicals

407

dienes, and styrenes. These reactions are characterized by very small activation energies (<20 kJ mol"1). Since the 1980's, Bauld and his coworkers evaluated the span of such cyclizations. Among them is also the cyclopropanation of alkenes with ethyl diazoacetate (Stufflebeme et al., 1986). Two typical examples are given in Schemes (9-33) and (9-34). Reaction 9-33 is conducted with a very electron-rich alkene, (£>l-(4'-methoxyphenyl)prop-l-ene (9.67) in dichloromethane at 0°C. It is initiated with 10 mol % of tris(4-bromophenyl)aminium hexachloroantimonate (9.68) as one-electron donor for the chain reaction. (Z)-l,2-Diphenylethene is less ionizable; therefore, cyclopropanation was carried out with the more potent single electron acceptor tris(2,4-dibromophenyl)aminium hexachloroantimonate (9.69). The yields are 64% and 81% for reactions (9-33) and (9-34), respectively.

(9-33)

9.67

C6H5

C6H5 , q eq

H5C200C-CHN2

+

II

>

Z\ HgCaCXJC^

(JKJ4) ^C6H5

9.68 : X = H 9.69 : X = Br

The electron transfer to and from diazo compounds was reviewed by Fry (1978) and by Bethell and Parker (1988). In a recent short review on applications of electrochemistry to organic synthesis (containing no examples involving diazo compounds), Utley (1994) stated that the "ready availability of electrochemical equipment ... has helped to lower the activation barrier which has formerly inhibited the involvement of mainstream organic chemists". This statement is quite correct, but, after having studied the literature on the electrochemistry of aliphatic diazo compounds and having written this and the following section, I rather incline to the opinion that it needs more to encourage chemists to use electrochemistry for organic synthesis, e.g., some procedure descriptions published in a journal specializing in synthetic methods, or, even better, in Organic Syntheses.

408

9 Miscellaneous Reactions Involving Diazo and Related Compounds

9.4 Oxidations and Reductions of Diazo Compounds As mentioned in the introduction to Section 9.3, we will discuss reactions with oxidation and reduction chemicals in this section. We will concentrate mainly on reagents that oxidize or reduce the diazo function and only marginally on reactions that involve reactions with other sites of diazo compounds. Diazoalkanes are fairly stable toward oxidation reagents. This is evident from one of the major reactions for their synthesis, the hydrazone dehydrogenation (see Subsect. 2.5.1). The diazoalkanes formed are stable against attack by the transitionmetal oxides used as dehydrogenation reagents. Diazo compounds are also not attacked by atmospheric oxygen at ambient temperature, although they react with ozone and in photosensitized oxygenations. Bailey et al. (1965) found that in a-diazocarbonyl compounds with a terminal diazo group ( —CH=N 2 ) the diazo function is replaced by an O-atom, i.e., a glyoxal derivative is formed primarily, but the final products result from CH bond cleavage. In other cases, however, the a,/?-dicarbonyl compound is stable. An example, described by Ursini et al. (1992), is the oxo-de-diazoniation (9-35) of various 6-diazopenicillanates (9.70, R = 4-NO2C6H4CH2 and other alkyl groups). The adiketone is obtained at -15 to -10°C in dichloromethane with ozone in 86-97% yield.

(9-35) COOR

COOR

9.70

The first photolytic reaction of a diazoalkane in the presence of dioxygen was made at a very early time. Staudinger et al. (1916 a) found that diazodiphenylmethane afforded mainly benzophenone. A second, historically important investigation was conducted by Bartlett and Trayler (1962), who were able to isolate the cyclic bisperoxide 9.72 in the photolytic oxygenation of diazodiphenylmethane and suggested that 9.72 was formed from the carbonyl oxide 9.71. Later, Murray and Higley (1973) demonstrated with 18O2 that benzophenone is not formed by cleavage of the cyclic bisperoxide (9.72), but in a competitive reaction of the carbonyl oxide (9-36). In addition, some minor products are indicative for radical intermediates that may be caused by the diradical mesomeric structure 9.71 c of the carbonyl oxide. With increasing knowledge and experience on the reactivity of singlet and triplet carbenes (see Sect. 8.1), and of singlet and triplet dioxygen (see Sect. 8.5) in the 1960's and 1970's, it seemed to be feasible to consider that a ^-molecule, as a highly electrophilic reagent, may attack the nucleophilic C(a)-atom of diazoalkanes

9.4 Oxidations and Reductions of Diazo Compounds

409

(CeH^Nz _D*_». (C6H5)2C: -Nj

(C6H5)2C=6— 6 -*-

*•

(C6H5)2C— O— 6

9.71 a

9.71 b

-<-

^ (C6H5)2C— O— 6 9.71 c

(9-36)

O— O (C6H5)2C/

0—0

9.72

(Bethell and Wilkinson, 1970) and that, therefore, a diazocarbonyl oxide (9.73), and even its cyclization product 9.74, may be intermediates before the release of dinitrogen.

R2c

R 2 2C/S

o—o~ 9.73

\

/

o—o

9.74

These investigations were started again by Murray's group, who trapped carbonyl oxides derived from singlet-oxygen oxygenation of diazo compounds with aldehydes (Higley and Murray, 1974) and with naphthalene (Chaudhary et al., 1976). In a typical experiment, Higley and Murray irradiated a solution of diazodiphenylmethane in acetonitrile containing Methylene Blue as sensitizer and benzaldehyde. The major products were 3,3,5-triphenyl-l,2,4-trioxolane 9.77 (26%)* and benzophenone (9.76, 67%), for which mechanism (9-37) was postulated. The last step of (9-37) is a 1,3-dipolar cycloaddition of the carbonyl oxide 9.71**. The dipolar reactivity of the carbonyl oxides is easily recognizable in its mesomeric structure 9.71 b (see also Table 6-1 in Sect. 6.2). A diazocarbonyl oxide of type 9.75 has been directly observed by IR spectroscopy at 10 K by Tomioka's group (Murata et al., 1990; see later in this section). The photosensitized oxygenation of a-diazo ketones also follows a slightly different pathway and leads to different products. Ando et al. (1979) found that openchain a-diazo ketones react in alcohols via carbonyl oxides, peroxides, and a CC bond cleavage to give carboxylates as final products (9-38). * In many papers, this intermediate is called an azonide in analogy to the similar type of compounds discovered by Criegee (see Criegee and Schroder, 1960, and Criegee's review, 1975) in the ozonolysis of alkenes. In that reaction a 1,2,3-trioxolane, i. e., an ozonide, is initially formed which, however, rearranges via a carbonyl oxide of type 9.71 and a carbonyl compound into a 1,2,4-trioxolane like 9.77 (see review of Kuczkowski, 1983). ** The formation of benzophenone (9.76) is probably also a 1,3-dipolar cycloaddition.

410

9 Miscellaneous Reactions Involving Diazo and Related Compounds

Ar2CN2 +

1

Ar2C

Q2

0—0" 9.75

D

x

L

(9-37)

o-oj

9.76

9.77

Y /v -

R'

- R"OH

0—0

Y

-

RCOOR" + R'COOR"

(9-38)

OOH

4,6-Di(tert-butyl)-2-diazo-l,2-benzoquinone (9.78), however, forms a cyclic peroxide (9.80), as shown by Ando et al. (1981 b) (9-39). The same reaction was independently investigated by Ryang and Foote (1981), who demonstrated that, before loss of N2, the e/zrfo-peroxide 9.79 can be observed. Scaiano et al. (1989) characterized the parent benzoquinone oxide, various derivatives thereof being obtained from the corresponding cyclic diazo ketones as well as from 9-diazofluorene *, and from diazodiphenylmethane by laser flash photolysis at room temperature. The parent benzoquinone oxide has an absorption maximum at 410 nm. The rate constants of 2-diazo-l,2-benzoquinone and of the carbene of this diazo compound with singlet oxygen were found to be l.OxlO 9 ]^" 1 s"1 and

(9-39)

9.78

9.79

* The photolytic oxygenation of 9-diazofluorene was investigated already by Ando et al. (1979).

9.4 Oxidations and Reductions of Diazo Compounds

411

5.0 x 109 M ~1 s"1, respectively. The carbonyl oxides can be scavenged by aldehydes as shown in Scheme 9-37. Tomioka's group (Murata et al., 1990, 1993 a, 1993 b) investigated the photosensitized oxygenation of l,3-bis(diazo)indan-2-one (9.81) in methanol-dichloromethane at 0°C and in an argon matrix (35 K, 9-40). The two major products are methyl 2-[(methoxycarbonyl)-carbonyl]benzoate (9.85, 34%) and dimethyl phthalate (9.90, 24%). By stopping the irradiation, the two diazo ketones 1-diazoindan-2,3-dione (9.82) and l-diazo-3,3-dimethoxyindan-2-one (9.87) can be isolated. The vinylogous diazo carbonyl oxide 9.86 has been directly observed by IR spectroscopy, when the reaction was run in the Ar matrix. Absorption bands at 945 cm"1 and 970 cm"1 are consistent with the structure 9.86. The authors assume that the attack of singlet oxygen on the diazo diketone 9.82 is followed by nucleophilic attack of methanol and leads, via a dioxetane (9.83) or a hemiacetal (9.84), to methyl 2-[(methoxycarbonyl)-carbonyl]benzoate (9.85) and, in case of the intermediate 9.87, via a hydroperoxide (9.88) and an e#do-peroxide (9.89) to dimethyl phthalate (9.90). The loss of N2O from the 1O2 adducts of 9.82 and 9.87 does not take place, probably because the cyclic 1,2,3-triketone formed in that reaction is an energetically unlikely product as a result of the unfavorable arrangement of the three carbonyl groups (see, e.g., Laird, 1979). Another experimental result is also consistent with the hypothesis that cyclic 1,2,3-triketones are not stable. 2-Diazoindan-l,3-dione (9.91) is oxidized by tert-butyl hypochlorite in ethanol to the 2-monoacetal 9.92 of indan-l,2,3-trione. The monoacetal undergoes hydrolysis to 2,2-dihydroxyindan-l,3-dione (ninhydrin hydrate; 9.93), but the trione itself could not be identified (9-41). The relatively recent use of dioxiranes (9.94: Murray and Jeyaraman, 1985; Adam et al., 1991) for organic oxidation is also interesting for diazo chemistry. Dimethyldioxirane (9.94, R = CH3) can be used for mild oxo-de-diazoniations of adiazocarbonyl compounds. Prato's group (Ihmels et al., 1991) used it for the synthesis of diketones, glyoxal hydrates, and for the formation of ethyl dihydroxyacetate from ethyl diazoacetate. The yields are excellent. It is noteworthy that diazocarbonyl compounds with oxidation-sensitive heterocyclic substituents undergo oxode-diazoniation exclusively. McKervey's group applied this method (Darkins et al., 1993) to the synthesis of homochiral TV-protected amino acids and dipeptides and, later (Darkins et al., 1994), for the first example of formation of an a-keto ester by dimethyldioxirane oxidation. Eleven homochiral TV-protected /?-amino-a-keto esters (9.96) were obtained from the corresponding a-diazo compounds (9.95) under neutral conditions in acetone in essentially quantitative yield, not involving detectable racemization (9-42). Previous syntheses of these compounds proceeded with extensive racemization. The diazo esters 9.95 were obtained via the Danheiser process (Danheiser et al., 1990a, see Scheme 2-55, Sect. 2.6) from the a-amino compounds. We are aware of only two investigations in which treatment with oxidizing reagents leads to attack of diazo compounds at positions other than at the diazo group. Air oxidation of 5-(diazoacetyl)-4,5-diphenyl-4,5-dihydropyrazole (9.97) in an ether hexane mixture yields the corresponding 3-hydroperoxide (9-43; Gulp et al., 1973). A surprising result is the oxidation of the benzyl group of 3-phenyl-4-diazo-5-benzylpyrazole (9.98) to a benzoyl group with chromic acid in 74% (9-44), observed by

412

9 Miscellaneous Reactions Involving Diazo and Related Compounds

9.4 Oxidations and Reductions of Diazo Compounds

413

C2H5OH

N2

+

(CH^C —O—Cl

>

(9-41)

NHR ' O

O

NHR'

II

N2 9.94

O

9.95

9.96

R = CH3 FT = protecting group R" = ami no acid residue

pB^S

''5^6

i—CH=N2

V

H

o *—*

^\ /

NH

p6^5

L-CO—CH=N2 \

(9-43)

HO—C

9.97

O N2+

N2+

CH2-C6H5

"*

^ M IN ^

H 9.98

^^

-

_

i JLI

O C-C6H5

^ M

^^ -H+

N2 J^/

^M

414

9 Miscellaneous Reactions Involving Diazo and Related Compounds

Farnum and Yates (1962). This is, of course, a borderline case between a diazo and a diazonio group and, therefore, it cannot be generalized. In contrast to the formation of aromatic hydrazines from arenediazonium salts, reduction of aliphatic diazo compounds is not used as a general synthetic method. As far as we know from the literature, the cause(s) for that discrepancy has (have) never been evaluated. We cannot offer an answer. We can only draw attention to a potential determinant in investigations on reactions in which aliphatic diazo compounds and hydride ions are involved. In their work on the generation of carbene anion radicals from a-diazocarbonyl compounds, Bethell et al. (1984) found that the first detectable product in the electrochemical reaction of 2-diazo-l,2-diphenylethan1-one was the 1,2-diphenylethenolate radical anion (see Scheme 9-29 in Sect. 9.3). Bethell and Parker (1986 a) investigated the kinetics and the products of that reaction in more detail. They came to the hypothesis that the azine 9.99, which is the final product under preparative conditions, is formed in a catalytic chain reaction in which a hydride-ion transfer is involved. Although the authors indicate that this hypothesis is tentative, it may be surprising, because there are at least two investigations in which a-diazo ketones react with sodium borohydride and this hydride ion donor attacked only the carbonyl groups (Severin and Lerche, 1970; Nikolaev et al., 1982).

/C-C6H5 /N=C\ N

O

C6H5

9.99

The discussion in this section demonstrated that the literature on oxidation and reduction of aliphatic diazo compounds is rather limited. This is also reflected in reviews. In the book on diazo and diazonium groups of the Patai series, they are discussed in the chapters of McGarrity (1978, p. 203), Ando (1978, p. 437), and Wulfman et al. (1978, p. 874). Each of these authors devotes only 1-3 pages to this subject. This is also the case in the monograph of Regitz and Maas (1986, p. 525). Ye and McKervey (1994, p. 1147) discuss the newer oxidations.

9.5 Dediazoniations of Alkenediazonium Ions We will discuss the dediazoniation of alkenediazonium ions separated from that of alkanediazonium ions (Chapt. 7) because alkenediazonium ions behave quite differently with respect to dediazoniation. As the diazonio group is bonded to an sp2-C-atom, this difference is not surprising. The reactivity of alkenediazonium ions is, however, also significantly different from that of arenediazonium ions in

9.5 Dediazoniations of Alkenediazonium Ions

415

which the diazonio group is also attached to an sp2-C-atom (see review by Zollinger, 1994, Chapts. 8 and 10). As discussed already in Section 2.10, the chemistry of alkenediazonium ions started only with the work of Bott in 1964. In occasional preceding investigations, alkenediazonium ions were postulated as metastable intermediates, e.g., in the nitrosation of 1,2-diphenylethenylamine, which yielded diphenylethyne in good yield (Curtin et al., 1965 a), in the aceto-de-amination of 3-amino-2-phenylindenone with sodium nitrite in acetic acid (1965 b), or in analogous acetolyses of ethenyltriazenes (Jones and Miller, 1967). Some further reactions with metastable alkenediazonium ions were reviewed by Bott (1964). The discovery of stable alkenediazonium salts by Bott initiated some investigations on the reactivity of these compounds, e. g. , with the hexachloroantimonate of the 2,2-diethoxyethene-l-diazonium ion (9.100). Saalfrank and Ackermann (1981 a, 1981 b) reported that 9.100 reacts with primary amines to give l//-l,2,3-triazoles. This process might be the result of an initial Af-azo-coupling reaction with the amine (characteristic of diazonium salts) with subsequent cyclization of the resulting triazene, or result from attack of the amine at the C(/?)-atom with formation of a diazoalkane that cyclizes (9-45).

c=c H5C20

N=N

H

C— C

SbCI6- + RNH2 N2+

H5C20

9.100 H5C20— C— CHN2

Later, Saalfrank and Weiss (1984) showed that three ethenediazonium hexachloroantimonates with aryl, methoxy, and piperidino substituents form oj,a>'-di-l//-l,2,3-triazolylalkanes in the reaction with a;,a/-diaminoalkanes (H2N — (CH2)«— NH2, n = 2,3,4 and 6). Hydrazines (9.102; R3 = H or 6 different organic groups) yield the l/f-l,2,3-triazoles 9.103 only with l-(4'-nitrophenyl)ethene-l-diazonium salt (9.101, R1 = R2 = H, R = 4'-NO2C6H4), but with 2,2-diethoxyethene-l-diazonium salt (9.101, Ri = R2 = OC2H5, R = H) the 2-diazohydrazones 9.104 (Saalfrank and Weiss, 1985). The influence of substituents on the weight of the two pathways in Scheme 9-46 certainly demonstrates the difficulty of rationalizing the reactivity of alkenediazonium ions. This fact is also evident from two investigations by Saalfrank et al. (1985, 1989) on the reaction of substituted ethenediazonium ions (9.105; R = R/ = C2H5O or R = CH3O, R' = 4-CH3OC6H4) with carboxylic acid hydrazides (9.106). They yield either 1,3,4-oxadiazoles (9.107), 6//-l,3,4-oxadiazines (9.108), or, via 9.108, 5,6-dihydro-4//-l,3,4-oxadiazines (9.109 and 9.110), again depending on the substituents (9-47).

416

9 Miscellaneous Reactions Involving Diazo and Related Compounds 1

R1

3 R

\

/

*

V

9.101

N—N

a

9.102

/R

''

R3

R2

R

~~C~~C~

V"T^(^N-J|' R

X (9-46)

R1 R3

N

c—

R

\ N2+

R' 9.105

N—N

9.107

Zollinger's group (Szele et al., 1983 a) studied the reactions of such an alkenediazonium salt with O-nucleophiles (ethers, alcohols, water, 2-naphthol) and with a secondary amine (diethylamine), since, in the latter reaction, the cyclization of Scheme 9-46 would not be possible. The reactivity of the ethenediazonium salt 9.100 towards the nucleophiles mentioned shows that it has the properties of the corresponding carbocation, since it can ethylate the nucleophile and is prone to attack at the C(/?)-atom of the original ethene-1-diazonium ion. The thermal decomposition pattern is typical of that for an oxonium salt. Reactions with amines are similar to those of ketene acetals. No product that could be explained in terms of an azo coupling reaction, e.g., with 2-naphthol, could be observed. The electrophilicity of the diazonio group is, therefore, low. N-Azo coupling products with azide ions have been postulated with good arguments, however, by Kirmse and Schnurr (1977) with certain short-lived ethene diazonium intermediates produced from nitroso oxazolidones.

9.5 Dediazoniations of Alkenediazonium Ions

417

In an additional investigation, Szele et al. (1983 b) investigated the methanolysis of (fluoren-9-ylidene)methanediazonium hexachloroantimonate (9.111), which can be considered as an ethenediazonium ion (9.111 a) or as a carbocation (9.111 b). This and similar compounds were postulated as intermediates in the solvolysis of nitroso oxazolidones (Newman and Okorodudu, 1969; Kirmse et al., 1979, and others), in the nitrosation of ethenylamines (Curtin et al., 1965a, 1965b) and in the acidic decomposition of ethenylamines (Jones and Miller, 1967). The methanolysis of 9.111 in methanol took place at — 20 °C and gave only 9-methoxyphenanthrene (9.112).

CH3OH - N2, - HSbCI6

9.112

In O-deuterated methanol, no labeled product was obtained, showing that the possible mechanism involves either the formation of an ethenyl cation (9.113) rearranging to an aryl cation (9.114) or the formation of a /?-alkoxycarbene (9.115) that rearranges to an arene. More detailed information on this unusual reaction can hardly be given. From the point of view of the broad interest in alkenyl cations (see Stang, 1973; Hanack, 1976; Stang et al., 1979; Hanack and Subramanian, 1990), better positive or negative evidence for the intermediacy of alkenyl cations like 9.113 was, therefore, highly desirable. Bott (1994) investigated the thermal dediazoniation of the

9.115

418

9 Miscellaneous Reactions Involving Diazo and Related Compounds

substituted ethenediazonium salts 9.116-9.119 in dichloromethane and in 1,2-dichloroethane in the presence of chloride ions. The products are consistent with the mechanisms (9-49) involving alkenyl cations (9.120 and 9.121). Compound 9.119 does not rearrange (product 9.122), but 9.116-9.118 form the corresponding rearranged products (9.123).

Br

\ C = CH—N

+ 2

SbCI6-

Br

9.116

S02.(SbCI5)2]~

9.119

(9-49)

The investigations of Bott and the groups of Saalfrank and Zollinger reported above demonstrate that reactions of 1- and 2-substituted ethenediazonium salts with various nucleophiles yield unexpected products. The structures of these products depend strongly on the substituents of the ethenediazonium salts. It is, therefore, hardly possible to use such diazonium salts as generally applicable synthons. As a consequence, it is not surprising that the groups mentioned did not continue their investigations into synthetic applications of ethenediazonium ions. More interesting is the use of the thermolabile /?-(acyloxy)alkenediazonium trifluoromethanesulfonates (triflates) 9.124 (R and R' = C6H5, CH3; R" = C6H5, CH(C6H5)2), synthesized by Lorenz and Maas (1987) in Oacylation of a-diazo ketones with benzoyl triflate or diphenylacetyl triflate in dichloromethane at — 70 °C

9.5 Dediazoniations of Alkenediazonium Ions

419

(9-50). When these solutions were slowly heated to room temperature, dediazoniation took place and the corresponding 1,3-dioxolium salts 9.125 could be isolated. The lower stability of /?-(acyloxy)alkenediazonium ions relative to that of /?-alkoxyethenediazonium ions is understandable on the basis of the lower electron donating power of the substituents. R O

R

R'

+ >-<

R"-< OTf

Q/

C= C ^U

X

N2

R'

O7 X C=

TfO-

V 0

R" 9.124 Tf = CF3SO2 R, R', R" see text

I -70°C to room temp. | ~ N2

R'

Tfcr R" 9.125

(9.59)

10 Metal Complexes of Diazonium and Diazo Compounds

10.1 Structure of Metal Complexes Containing Arenediazonium Ions as Ligands The terms 'complex' for chemical structural entities and 'complexation' for the phenomenon of complex formation are used in chemistry for a large variety of interactions between two or more molecules or ions held together by forces that are not clearly 100% covalent bonds or 100% Coulomb attractions between cations and anions. Although we know today that these classical types of interaction are very rarely realized in pure form (if ever), these two extreme cases are an excellent working basis for the large majority of chemical problems on which chemists worked and still work for scientific and industrial purposes. There are molecular complexes, however, the formation and existence of which are not understandable with only the two principles mentioned. Molecular complexes may be held together by hydrogen bonding, by ion pairing, by van der Waals forces, by 7t-acid to Ti-base interaction, by backdonation, by solvent reorganization ('iceberg effects'), etc. — in other words, by a plethora of quite different phenomena. The result is the fact that the term complexation embraces a large number of fairly different effects. This chapter demonstrates that this statement is applicable to diazo compounds. Therefore, the reader should not be surprised to find here two sections on diazo and diazonium compounds as ligands in metal complexes and, in the volume on aromatic diazo chemistry (Chapt. 11), a discussion of host-guest complexation chemistry. It appears appropriate to include complexes with arenediazonium ions as ligands in the present volume and not in that on aromatic diazo chemistry because here these complexes can be discussed in the context of the corresponding aliphatic compounds (Sect. 10.3) and of the addition products of dinitrogen-to-metal complexes (Sect. 3.3). Interactions between transition metals and arenediazonium ions were already known in the early history of diazo chemistry. Since the discoveries of Sandmeyer (1884), Pschorr (1896), Meerwein et al. (1939), and others, various metal-catalyzed replacements of the diazonio group by other substituents became important synthetic methods in organic chemistry. We have discussed these reactions in several sections of our first book (Zollinger, 1994, Chapts. 8 and 10). Very little work was carried out, however, on the structure and properties of the primary addition products of transition metals on diazonium ions before organometallic chemistry started to grow strongly in the 1950's. As briefly mentioned in Section 1.1, the first isolated and well characterized transition metal complex conDiazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

422

10 Metal Complexes of Diazonium and Diazo Compounds

taining an arenediazonium ion as ligand was dicarbonyl(cyclopentadieno)(4-methoxybenzenediazenido)molybdenum * [Mo(//5 - C5H5 )(CO)2(N2 - C6H4 - 4 - OCH3)]. King and Bisnette (1964) obtained this complex by displacement of a carbonyl group in tricarbonyl(cyclopentadieno)molybdenurn by the arenediazonium ion**. It is likely that the majority of readers of this book will be scientists who do not work, or perhaps only marginally, in organometallic chemistry. It is, therefore, appropriate to give a very brief summary on concepts and nomenclature in this growing and fascinating field of general chemistry, which started to bridge inorganic and organic chemistry since about 1950, after a full century of almost completely separate development in these two classical fields of chemistry***. We therefore start this section with a discussion of some terms that are used to describe structures of organometallic compounds. Originally, organometallic chemistry was concerned with compounds containing metal-carbon bonds. Much earlier, namely already in the 19th century, metal complexes with organic ligands, but metal-heteroatom bonds (mainly M-O, M-N, and M-S bonds) were known, investigated structurally and used technologically (e.g., metal-complex dyes). As aliphatic and aromatic diazo compounds are, in most cases, bound to the metal atom as ion with one or both nitrogen atoms, they are not organometallic compounds in a strict sense. Nevertheless, their chemistry is, with respect to synthetic methods and structures, very closely related to that of organometallic compounds. These similarities are reflected even in textbooks of inorganic chemistry (e. g., Cotton and Wilkinson, 1988) or in monographs on organometallic chemistry (e.g., Collman et al., 1987; and Pruchnik, 1990). There are several useful reviews on organometallic diazo compounds, in part concentrating on additions of diazoalkanes or of diazonium ions, but in most cases, also covering related complexes, e. g., dinitrogen complexes (which may add alkyl groups to the outer nitrogen atom, see Sect. 10.2) or complexes with diazenes [M(NR=NR)J, hydrazines [M(NR2NR2)], hydrazides(l-) [M(NR-NR2)] and hydrazides(2-) [M(NNR2)]****. As we will see, some of these complexes are formed in reactions with diazo compounds, and some may form diazenido complexes by dissociation of the NR bonds*****. * In the newer literature on metal complexes with arenediazonium groups, this ligand is called aryldiazenido. We may add that the prefix aryl- became questionable in our opinion, since the word aryldiazonium was replaced by arenediazonium (IUPAC, 1979). Nevertheless, we will use aryldiazenido for the class and replace 'aryl' by 'arene' only in cases like that mentioned above. In complexes containing Ar - NN - H groups we use the term 'aryldiazene' in concordance with the literature. We label the two nitrogen atoms in all these ligands a and /?, relative to the aromatic ring, not relative to the metal. Organometallic chemists number, however, the nitrogen attached to the metal 1. ** Earlier, unsuccessful attempts to synthesize metal complexes with diazenido ligands were undertaken by Schrauzer (1961), and by Clark and Cookson (1962) (see Sect. 10.2). *** We emphasize 'almost completely', because there are important exceptions, e. g., Alfred Werner (1866-1919, Nobel Prize 1913) whose work on the stereochemistry of metal complexes was influenced by van t'Hoff's and Le Bel's concept of the asymmetric carbon atom. **** Tne number in parenthesis indicates whether the mono- or dianion of the hydrazine derivative is the ligand. ***** In all these formulae above, R may be H, an alkyl, or an aryl group.

10.1 Structure of Metal Complexes Containing Arenediazonium Ions as Ligands

423

Most important for this chapter are the two reviews of Sutton (1975, 1993). His second review contains some 300 references — and it is not intended to be comprehensive! There are also chapters on diazenido complexes by Bruce and Goodall (1975) and by Niemeyer (1978) in the volumes on hydrazo, azo, and azoxy compounds in the Patai series. The respective chapter of Johnson et al. (1987) in Comprehensive Coordination Chemistry contains a discussion of diazenido complexes. In 1994, complexes containing diazenido ligands were known for 19 transition metals, as shown in the corresponding part of the Periodic Table (Table 10-1). We have only included complexes that, in accordance with the present definition of organometallic compounds (see above), are not chelate complexes of organic compounds such as salicylic acid (2-hydroxybenzoic acid) or 2,2/-dihydroxyazo and similar dyes whose coper, cobalt, chromium, and nickel complexes are widely used industrially. It is interesting, viewed particularly from the experience of classical coordination chemistry or metallized dye technology, that no diazenido complexes of copper and nickel could be found hitherto in the literature. Table 10-1. Transition metal part of the Periodic Table. Bold-faced symbols: Diazenido complexes described. Symbols in light type brackets: No organometallic compounds with diazenido ligands found in the literature (also not for lanthanides and actinides).

[Sc]

Ti

V

Cr

Mn

Fe

Co

[Ni]

[Cu]

[Zn]

[Y]

Zr

Nb

Mo

Tc

Ru

Rh

Pd

[Ag]

[Cd]

[La]

[Hf]

Ta

W

Re

Os

Ir

Pt

Au

[Hg]

The centers of interest in organometallic chemistry are the geometrical arrangement of the atoms and the type of bonding between metal atoms or ions and organic ligands. Atoms or groups in either of the two reaction partners that form a covalent bond are regarded as one-electron donors. Any compound with a reacting electron pair is a two-electron donor. Groups that can form a single bond and, at the same time, donate an electron pair can be considered as three-electron donors. A simple example is the acetate ion which, as a ligand for a metal atom or ion (M), is either a one- or a three-electron donor (10.1 and 10.2, respectively). There is an enormous number and diversity of ligands, ions, and molecules that can react with metals. A recent extensive monograph (Pruchnik, 1990) mentions 70 classes of ligands (but not diazenido complex-forming compounds!). In general, formal charges of metal ions, ligands, and ligand groups are not given, but the total charge of a complex is, if it is an anion or cation. In the nomenclature of a complex, the oxidation state of the metal may be mentioned in parentheses immediately after the name of the metal. A \i in front of a ligand indicates that it bridges two or more metal atoms (number given as subscript). The letter r| with a superscript indicates to how many atoms of a ligand the metal is bound (e. g., TI 5 for the cyclopentadienyl anion ligand). The prefix T|l is used only in cases where, in addition to a one-bond addition (e.g., in 10.1), bonds to two ligand atoms may also be feasible (10.2).

424

10 Metal Complexes of Diazonium and Diazo Compounds O

M—
11 C.

Q

X M M

ou

V-CH ,C — UH3

x x

10.1

-

10.2

An informative table of common organometallic ligands with names, formal charges, and number of electrons donated is given by Collman et al. (1987, p. 24). On the basis of this introduction, we will now discuss the structures found for aryldiazenido complexes. For an organic chemist, the most surprising observation in metal complex formation of arenediazonium ions is the fact that the nitrogen atoms have the function of electron donors and not electrophiles as in additions to organic and (nonmetallic) inorganic compounds. We shall return to this phenomenon later in this section. There are at least eight types of structure discussed for aryldiazenido complexes (Carroll and Lalor, 1973; Collman et al., 1987; Cotton and Wilkinson, 1988; Sutton, 1993), namely singly and doubly bent structures (10.3 and 10.4) and, less common, bridging bimetallic structures (10.5 and 10.6). In addition, there are four types of structure for which, today, only a few well-documented complexes are known, the side-on (10.7) and the linear type (10.8). The latter is based on a (substituted) boranediazenido group (see below). Finally, there are the interesting bimetallic structures of the cation 10.9, with a \i2-T\ ^aryldiazenido bridging mode, found by Sutton's group (Einstein et al., 1990)*, and 10.10, in which the aryldiazenido group is not bridging parallel, but normal to the cobalt-cobalt bond (DeBlois et al., 1988). In structure 10.3, the oxidation state is not changed by this type of complex formation, which can be regarded as derived from ArN^ in which, however, ArN2+ is a three-electron donor! The M — N — N bond is almost but not quite linear, and the Ar

Ar

If U

," ^

M

M

I

I

10.3

M' N

A

ff U

II

IIM

MM'

10.4

Ar

10.5

10.6

Ar

Ar N 10.7

N II N II M 10.8

Ar _ /

OC,.,, /

\

Cp

ocv _,,,Cp

~~ ..... -r- ..... co ~~ 00

CO 10.9

C6H5 10.10

* A similar diosmium complex was found by Churchill's group (Samkoff et al., 1984).

10.1 Structure of Metal Complexes Containing Arenediazonium Ions as Ligands

425

N —N —C bond angle may be significantly larger than 120°. For example, in the Run-complex 10.11 the Ru-N-N angle is 171.2° and the N - N - C angle 137.1° (Haymore and Ibers, 1975 b). The iron(0)-complex 10.12, however, has corresponding angles of 179.2° and 124.2° (Haymore and Ibers, 1975 a). A table of dimensions, given by Barrientos-Penna et al. (1980) shows that the majority of singly bent diazenido complexes have N —N —C angles near 120°. C6H4-4-CH3 / N II N Ck... 1 ,,.P(C6H5)3 )3P^ |U>ci Cl

P(C6H5)3

oc,, |

^Fe-N=Nx p

(CeH5)3

10.11

10.12

For an organic chemist, the formal view of the arenediazonium ion as a three-electron donor can be better understood if the diazonium ion is considered to be coordinated through the o lone-pair on the /^-nitrogen together with strong back donation of electrons from the filled dn or hybrid dprc metal orbital to the empty pjc* orbital on Np, as shown in Sutton's structure 10.13a (1975). The population of TC* orbitals on ArNi1" should leave the M - N - N and N - N - C angles close to 180°. Structure 10.13 b, on the other hand, indicates by its valence-bond picture a N - N - C angles of 120°, although still an M - N - N angle of 180°. Orbital overlap or, in other words, electron flow, is in the opposite direction to form the formal o and 7i bonds between M and N.

:N==N—Ar \->>

10.13b

10.13a

As discussed in Section 2.6 the diazo group in diazocyclopentadiene and its derivatives has significant diazonio group character. This property is also reflected in the formation of diazenido metal complexes. Schramm and Ibers (1978, 1980 a) substituted the carbonyl ligand in the iridium complex [IrCl(CO)(P(C6H5)3]2] with 2,3,4,5-tetrachlorodiazocyclopentadiene. In the product [IrCl(NrC5Cl4)[P(C6H5)3)2] (10.14) the angles Ir-N p -N a and N p -N a -C were found to be 174.9° and 141.0°, respectively. This complex corresponds, therefore, to the singly bent type 10.3. One or two additional ligands, e. g., P(CH3)3 or NO +, can be added easily to the metal of this four-coordinate complex (Schramm and Ibers, 1980b).

426

10 Metal Complexes of Diazonium and Diazo Compounds

Cl

L = P(C6H5)3

10.14

The doubly bent aryldiazenido group (10.4) is characteristic for contributing one electron to a two-electron, two-center o-bond with the metal. Formally, therefore, such a one-electron donor ligand is an arenediazo anion (ArNf in 10-1 A), but the synthesis is still based on arenediazonium ions. They attack, however, an electronrich metal atom or, in other words, the metal atom undergoes a formal one-electron oxidation (10-1B). -Ar M t"N'=N—;

^N—Ar (10-1) M-N

N—Ar

The doubly bent aryldiazenido metal complexes should, therefore, correspond structurally to organic azo compounds. One expects angles of about 120° at both nitrogen atoms and (Z)/(E) geometrical isomerism. As shown by Gaughan and Ibers (1975) in the first X-ray structure determination of a doubly bent (£>aryldiazenido metal complex, the expectation with respect to the angles is fulfilled quite well: the rhodium complex 10.15 (Scheme 10-2) has M - N - N and N-N-Ar angles of 125.1° and 118.9°, respectively. The M-N distance is considerably longer (196.1 pm)

(10-2) (C6H5)2P'

pp.6 10.15

Cl

70.7 Structure of Metal Complexes Containing Arenediazonium Ions as Ligands

427

than that of the singly bent aryldiazenido complexes (170-180 pm), as expected on the basis of the one-electron donor formalism for doubly bent complexes. The interesting type of diazenido complex 10.7 was found by Latham et al. (1986 a) when they made an X-ray investigation of the dichloro(r|5-cyclopentadieno)-(r|2phenyldiazenido) titanium complex (10.16), which was synthesized by the same group (Dilworth et al., 1978, 1983). It is, as shown in 10.16, a side-on diazenido complex*. The bonds between the Ti-atom and the two N-atoms form an almost perfect isosceles triangle with angles of 34.9°, 70.6° and 74.5° at the Ti-, N(jff)- and N(a)-atoms, respectively. The C-N a -Ti angle is 159° and the C-N a -N p angle is 126.6°. The NN bond length is 121.9 pm. A basically similar structure had been found earlier by Schramm and Ibers (1980 c) for a ruthenium complex with a tetrachloro(diazocyclopentadienyl) ligand [Ru(CO)2(N2C5Cl4)(PPh3)2]. The closely related iridium complex 10.14, however, has a singly bent diazenido ligand with the Np atom as sole coordination site! The structure 10.16 reflects a general property of titanium, namely a preference for TI 2-coordination to two N-atoms (see Durfee et al., 1990). This effect has also been documented for organohydrazide(l —) complexes of titanium (Latham et al., 1986b).

10.16

We are aware of only one diazenido metal complex that corresponds almost to the linear type 10.8, namely the dihydro(triphenylphosphino)[l-(dimethylsulfonio)-10(10)-boranediazenido]ruthenium complex [(RuH2[N2B10H8S(CH3 )2 ] [P(C6H5 )3) ] (10.32; see Sect. 10.2). Schramm and Ibers (1977) determined its structure by an Xray analysis. They found that the Ru-Np-N a angle is 175.9° and the N(3-N a -B angle 172.7°. In so-called bridging aryldiazenido complexes either two metal atoms are bonded to the N(P)-atom (10.5), or one metal is bound to each of the two N-atoms (10.6). The first type is documented by the (tetracarbonyl)(diazenido)manganese complex [Mn(N2-C6H5)(CO)4]2 (10.17; Abel et al., 1974). The two Mn-N(p) bonds have almost the same length (203.1 pm and 202.1 pm), indicating similar character. The two Mn —N(P) —N(a) angles, however, are quite different (119.6° and 134.4°, for the angles to the Mn-atoms in (E)- and (Z)-position, respectively, relative to the phenyl group). There is obviously steric repulsion between the phenyl group and the (Z)-oriented Mn-atom. The diazo complex 10.9 is structurally interesting, because the two iridium atoms are bonded to the two N-atoms of the same diazenido ligand, thereby resulting in parallel NN and Mr bonds (Einstein et al., 1990). Furthermore, it is important to * The side-on double coordination is indicated in the short-hand description of such complexes by the prefix r|2 in analogy with r|5 for cyclopentadienyl complexation.

428

10 Metal Complexes of Diazonium and Diazo Compounds

N CO N[I CO OC^/ x!/CO

Mn Mrv OC' 1 ^ i "CO CO CO

10.17

note that this binuclear complex was obtained by the reaction of 4-methoxybenzenediazonium ion (= ArN/) with 2 equivalents of the mononudear bis(ethene) complex [IrCp(C2H4)2] *, i. e., the Mr bond was formed in the same reaction as the addition of the arenediazonium ion. The binuclear cobalt complex 10.10, however, contains an NN bond that is not parallel, but normal to the bond between the two cobalt atoms and each of the azo Natoms is bonded to both metal atoms (DeBlois et al., 1988). Some other interesting structures of binuclear complexes with diazenido and related ligands will be mentioned in the context of syntheses, as the bonding of the ligand is not fundamentally different from those summarized by the structures 10.3-10.10. For obvious reasons, the most informative method for the elucidation of metal complex structures is X-ray analysis. When this was less easily available, IR spectroscopy yielded the highest number of reliable results. This was particularly true when Haymore et al. (1975) showed that the NN stretching vibration, which normally overlaps with aryl vibrational modes, can be mathematically decoupled in 2H- or 15 N-labeled complexes. Complexes of type 10.3 can be generally identified by the presence of frequencies above ca. 1650 cm"1, those of type 10.4 by low frequencies (less than ca. 1500cm"1). The other types mentioned earlier in this section (10.5-10.10) are much more difficult or even impossible to detect on the basis of IR spectra only. Within a given structural type, however, IR spectra gave information on electron flow when changing ligands, d^-p^ back-donation from the metal to ligands, at an early time of investigations on metal complexes with diazenido groups (King and Bisnette, 1966; Fischer and Sutton, 1973; and others). Haymore and Ibers (1975) suggested correction parameters for NN vibration frequencies, when structural parameters of a given type were changed (e. g., period and group of the metal in the Periodic Table, charges, ligands, and coordination numbers). These correction parameters lost importance due to their restricted applicability (structure type) and due to the better availability of more precise information from X-ray structure analysis. 1 H NMR spectra yield, in most cases, insufficiently specific data**. Interesting conclusions could be drawn, however, from 19F NMR data. Cenini et al. (1971) and * Cp = cyclopentadienyl. ** An important result, however, was the evidence that protonation of diazenido ligands takes place at the N-atom adjacent to the metal, as shown by Liang et al. (1973) on the basis of 15N - !H coupling constants.

70.7 Structure of Metal Complexes Containing Arenediazonium Ions as Ligands

429

Lalor's group (Carroll et al., 1974) investigated platinum(aryldiazenido) complexes with 4-substituted benzenediazonium ions and with the three isomeric fluorobenzenediazonium ions as ligands. They were able to detect decreasing Pt — N double bond character when electronegative substituents are present. Taft et al. (1973) measured the 19F NMR chemical shifts of seven pairs of molybdenum and tungsten complexes each containing a 3- and a 4-fluorobenzenediazenido ligand. The shift difference 8^-8^ is between -0.14 and -5.02 (in ppm), and reflects the electronic effects of the sum of the other ligands on the aryldiazenido ligand via the metal atom. The less shielded the fluoro atom at C(4) is relative to the fluoro atom at C(3), the less electron flow into the aryldiazenido ring has taken place. It is surprising that Taft did not apply his dual substituent parameter treatment (Taft, 1957; Ehrenson et al., 1973; see also Zollinger, 1994, pp. 150 and 168) to metal complexes with diazenido ligands. This approach was made by Garner and Mays shortly afterwards (1974) because the difference 8p-8w represents an overestimation of the resonance effects as symbolized by structures like 10.18 for a 4-fluorobenzenediazenido platinum complex. Garner and Mays investigated neutral [PtCl(N=NAr)[P(C2H5)3)2] and cationic [Pt(N=NAr)(L)[P(C2H5)3]2]+ complexes (Ar = 4- and 3-fluorophenyl). They found that in the neutral complex the metal, together with the two phosphine and the chloro ligand, acts through the azo bridge as a weak 7r-donor and as a weak o-acceptor. In the cationic complexes, the corresponding parts of the complex are better o-acceptors but do not change significantly as 7i-donors. This result is in accordance with Button's structure 10.13 a for back-donation. In addition, Garner and Mays, in the analogous cationic complexes 10.19, investigated the stability in dediazoniation following Scheme 10-3. The stability follows the sequence L = NH3 « pyridine > P(C2H5)3 « RNC > CO, demonstrating the overall electron-donating effect of the grouping Pt(L)[P(C6H5)3]ih.

10.18

[pt(4-N2-C6H4X)(L){P(C6H5)3}2]+

""2

>

[Pt(4-C6H4X)(L){P(C6H5)3}2]+

10.19 X = N(C2H5)2, N(CH3)2, OCH3, H, CH3, F, NO2

Based on our own experience with dual substituent parameters, more extensive application of this tool for the investigation of back-donation phenomena in organometallic compounds is highly recommended. Theoretical investigations have not yet, so far as we are aware, provided a basis to account for the relative importance of a and n components of the bonding in diazenido complexes. This problem was studied for carbonyl complexes by

430

10 Metal Complexes of Diazonium and Diazo Compounds

Bauschlicher and Bagus (1984), but even for structurally simple molecules like MCCO)^ (x = 4, 5 or 6) substantial approximations were necessary, which then made the final results uncertain. As stated by Cotton and Wilkinson (1988, p. 59), we still have to rely on experimental evidence in attempting to understand bonding in metal complexes of re-acid ligands. Semiempirical concepts may be helpful for better understanding the character of metal-ligand bonds in general. Pearson (1982, 1991) showed that electronegativity and hardness of a series of ligands are correlated to the bond strength in such complexes. The order with respect to the fractional number of electrons transferred (A7V) is related to the electronegativity (x) and the hardness (rj) of the donor (D) and acceptor (C), as given in (10-4). For a given metal, the calculated values of A7V for a series of ligands correspond fairly well with experimental values. Unfortunately, Pearson's work does not include diazenido ligands. (XC-XD)

10.2 Synthesis of Aryldiazenido Metal Complexes There is a variety of methods for the synthesis of metal complexes with diazenido ligands and there are also some syntheses involving reactions of metal complexes with arenediazonium ions that yield complexes with other ligands, e.g., diazenes and, vice versa, diazenido metal complexes can be obtained in some cases with other reagents than diazonium ions. The first reported diazenido metal complex was obtained by King and Bisnette (1964) by ligand exchange, as shown in (10-5): one of the three carbonyl groups in the molybdenum complex 10.20 was replaced by an aryldiazenido ligand (10.21) in tetrahydrofuran. The 18-electron Mo configuration requires the aryldiazenido ligand to be a three-electron donor; the anionic complex 10.20 becomes a neutral product (10.21) by this substitution. Similar diazenido complexes were found with the iron-phosphine complex [Fe(CO)3[P(C6H5)3]2] by Ibers and Haymore (1975): one carbonyl group is replaced by a diazenido ligand. An X-ray structure determination demonstrated a singly bent FeN2Ar structure (Sect. 10.1, type 10.3).

ArfV

10.20

-

•*-

10.21

• ™

(10-5)

70.2 Synthesis of Aryldiazenido Metal Complexes

431

Many attempts to replace a carbonyl by an aryldiazenido ligand in transition metal complexes containing only carbonyl ligands, failed, however, as King and Bisnette made attempts with [Y(CO)6]", [Mn(CO)5]~, and [Co(CO)4]~ in 1964, and Schrauzer (1961), Clark and Cookson (1962) earlier. The latter two investigations, indeed, represent the first reactions of organometallic compounds with arenediazonium ions, but only vigorous evolution of N2 and CO was observed. Apart from ligand replacements, simple addition of arenediazonium ions to rhodium and platinum complexes was already known in the early 1970's by Cenini et al. (1971), by Ibers' group (Gaughan et al., 1973; Gaughan and Ibers, 1975) and by Laing et al. (1973). Cenini's group described the synthesis of a series of cationic (aryldiazenido)[tris(triphenyl)phosphino]platinum complexes 10.22 by reaction of 4-substituted arenediazonium tetrafluoro- and tetraphenylborates with [tris(triphenyl)]phosphino platinum. Scheme 10-6 shows that addition of diazonium salts — in contrast to replacement — leads to an increase in the oxidation state of the metal. In an analogous way Ibers' group synthesized the rhodium complex 10.15, which has already been discussed in Section 10.1. [pt{P(C6H5)3}3] + 4-XC6H4N2+ Y(10-6) [ Pt(4-XC6H4N2){P(C6H5)3}3]+ Y-

10.22 X = N(C2H5)2, N(CH3)2, OCH3, H, CH3, F, NO2 Y = BF4> B(C6H5)4

(Trimethylsilyl)phenyldiazene (10.23) is an interesting alternative to arenediazonium salts, although the N(/?)-Si bond is clearly covalent. Abel and Burton (1979; see also earlier references there) used it to replace a carbonyl group in monobromo(pentacarbonyl)manganese (10-7). The trimethylsilyl part of 10.23 (as 2 [Mn(CO)5Br] + 2 (CH3)3Si-N2-C6H5

10.23

C6H5

(10-7)

N CO

CO

co / N \'/ Mn Mn

I XNX £ ^CO CO CO

10.24

+ 2 (CH3)3SiBr + 2 CO

432

10 Metal Complexes of Diazonium and Diazo Compounds

leaving group) reacts with the Br-atom of the Mn complex. Therefore,it is not a simple substitution and, indeed, as an X-ray structure determination shows, a binuclear complex with bridging diazenido ligands (10.24) is formed. We emphasize that complex 10.24 has only a superficial similarity to the structure of the binuclear Co-complex 10.10 in Section 10.1! The same reagent 10.23 was also used by Leigh's group (Latham et al., 1986a; Dilworth et al., 1978, 1983) in the synthesis of the titanium complex 10.16, which we discussed in Section 10.1 because of its side-on diazenido ligand. There are several methods for syntheses of diazenido metal complexes that are, in a certain sense, related to the direct replacement and the addition of arenediazonium ions discussed above. In hydrido complexes (e. g., 10.25) a ligand can be substituted by an arenediazonium ion (10-8). In the diazenido complex formed, the hydrido ligand is rendered sufficiently acidic to be subsequently lost (10-9) from the metal. Attack by chloride ion at the metal, followed by protonation of the diazenido ligand (10-10), gives the aryldiazene complex 10.26. Although this sequenc of reactions leads to aryldiazene complexes, the syntheses and properties of which are outside the scope of this book, we mention this method because diazenido complexes are formed as intermediates, as shown by Henderson (1985). The deprotonation of diazenes to diazenido complexes, i.e., the reaction of step (10-9), does not, however, work in some other cases, as shown by Bordignon's group (Albertin et al., 1986), although it has been used since Parshall found that pathway to diazenido complexes in 1965 (newer literature see Albertin et al., 1986, 1987, 1989; Amendola et al., 1990).

[RhHCI2{P(C2H5)(C6H5)2}c]

+

4-X-C6H4-N2+ (10-8)

[RhHCI2(N2— C6H4— X){P(C2H5)(C6H5)2}2]

+

H+

- |! [RhCI2(N2— C6H— X){P(C2H5)(C6H5)2}2]

[RhCI3(HNN— C6H4— X){P(C2H5)(C6H5)2}2] 10.26

The overall reaction from 10.25 to 10.26 is an insertion into a metal-hydrogen bond. It is, however, only an apparent insertion, as the Rh - H bond dissociates in the diazene ** diazenido equilibrium (10-9), as already emphasized by Sutton in 1975. Other interesting cases are the reactions of tungsten mono- and bis-hydrido complexes with diazonium salts. The monohydrido complex 10.27 yields the aryldiazene complex 10.28 (Smith and Hillhouse, 1988) in an 1,1-insertion (10-11). The bishydrido complex 10.29 (10-12), however, adds one of the two H-atoms at the

10.2 Synthesis of Aryldiazenido Metal Complexes O OC^ | /P(C6H5)3 /W^ (C6H5)3P/ | ^CO H

433

O ArN2+

*-

OC^ | /P(C6H5)3 .\W (C6H5)3P^ | >0 ^N^

hr

(10-11) ^

l

^N

| Ar

10.27

10.28

. /H W.

(C5H5)2WH2 + C6H5N2+

(10-12)

10.29

nitrogen adjacent to the phenyl ring, i.e., it is a 1,2-insertion. The product is a phenylhydrazido(2 —) complex (Carroll and Sutton, 1980). The diversity of mono- and bishydrido complexes can be exemplified also for cobalt complexes. In contrast to the apparent insertion into W —H bonds (see above), the monohydride [CoH[P(OC2H5)2(C6H5))4] is only oxidized in the presence of arenediazonium salts. The cationic bishydride [CoH2[P(OC2H5)2(C6H5)}4] + , however, yields the aryldiazenido complex [Co(N2Ar)[P(OC2H5)2(C6H5))4]2+ (Albertin and Bordignon, 1990; Albertin et al., 1990)! Most interesting is also Sutton's remark (1993, p. 1016) that all attempts to synthesize nickel complexes with diazenido groups have failed. The few diazonium ions that are found in the chemistry of polyhedral boron hydrides (see Sect. 3.2) also form diazenido complexes with transition metal derivatives. Knoth (1972) found various ways (Scheme 10-13) to add the ligand 10-diazonio-l-(dimethylsulfonio)decaborane (10.31) * to ruthenium complexes to obtain complex 10.32, namely by addition to [Ru(N2)H2[(C6H5)3P)3] (10.30) under release of N2, or to [Ru(Cl)2[(C6H5)3P)4] (10.33), or to [RuHCl[(C6H5)3P)4] (10.34), followed by addition of HC1. The primary product with the two chloro ruthenium complexes is the complex [Ru(Cl2)[(C6H5)3PJ3N2B10H8S(CH3)2], which is extremely explosive when dry. The latter is hydrogenated by NaBH4 to give the complex 10.32, which is fairly stable. Diazenido complexes can also be obtained by what may be called intra-complex diazotization, namely by reaction of a complex containing a nitroso ligand with an aromatic amine. Diazotization with nitroso complexes as nitrosating reagent is known (see Sect. 2.3). Bowden et al. (1973, 1977) found that (nitrosyl)ruthenium complexes like [Ru(bipy)2(NO)Cl]2+2PF^" react with primary aromatic amines to form the corresponding aryldiazenido complex [Ru(bipy)2(N2Ar)Cl]2+2PFg~. The For the synthesis of this and related inorganic diazonium compounds, see Sect. 3.2, p. 105.

434

10 Metal Complexes of Diazonium and Diazo Compounds [Ru{(C6H5)3P}3(HCI)(C6H5CH3)] + N2 (+ AIEt3)

[Ru{(C6H5)3P}3(N2)H2] 10.30

h N2B10H8S(CH3)2 N

2

10.31

[(C6H5)3P]3RuH2 (10-13)

O =B o

= H

10.32 H NaBH4

[Ru(CI2){(C6H5)3P}3{N2B10H8S(CH3)2}] >x+HCI

4]

+ NzBHrt^CHafe

[Ru(HCI){(C6H5)3P}4{N2B10H8S(CH3)2}]

10.33

[Ru(HCI){(C6H5)3P}4] + N2B10H8S(CH3)2 10.34

general applicability of this method is, however, doubtful (see remark of Sutton, 1975, p. 460). In this context, the work of Laali and Murray (1990) may be mentioned. Aiming at synthesizing (carbonyl)chromium complexes containing aryldiazenido ligands, these authors studied the reaction of nitrosyl ions with tricarbonyl(2-methylaniline)chromium. Diazotization competes with NO + attack at the metal center and decarbonylation. Complex mixtures of products are obtained. They indicate that the Cr(CO)3-complexed diazonium ion is unstable and undergoes dediazoniation, even at low temperature, predominantly by homolytic pathways. Competing heterolytic dediazoniation products are observable in highly ionizing solvents of low nucleophilicity, such as CF3SO3H, FSO3H, and CF3CH2OH.

10.2 Synthesis of Aryldiazenido Metal Complexes

435

Based on the classical work of King and Bisnette (1964, see introduction to this section), the ligand replacement in (cyclopentadienyl)(phosphine) complexes of molybdenum has been greatly expanded by Lalor's group (see Ferguson et al., 1990; Deane et al., 1990, and references given therein). Bis(aryldiazenido)(cyclopentadienyl)(triphenylphosphine) complexes [MoCsHs^ArX^AOf P(C6H5 ) 3 j] + PF6~ with two different aryldiazenido ligands can be synthesized by stepwise replacement with two different arenediazonium ions. They are useful for the synthesis of a variety of other bis(aryldiazenido)molybdenum complexes. For the synthesis of molybdenum complexes with more than two diazenido ligands, diazonium ion addition or replacement is, however, no longer the method of choice; condensation of di- and polyoxomolybdate complexes with hydrazines is preferred. They were investigated mainly by Zubieta's group. We show Zubieta's work on two typical examples. Hsieh and Zubieta (1985) synthesized a tetranuclear oxomolybdate complex containing four phenyldiazenido ligands (10.36) by reaction of [MoO2(butane-2,3-diolate)2]-(butane-2,3-diol) (10.35) with excess phenylhydrazine (10-14). CH3 C,H_CH3 CHOH

-2

O

HOH

o \

+ >4 C6H5NHNH2 + N(C2H5)3

in CH3OH/H+

O

Mo

O

/ / \ \ Mo H3CO OCH3 3 3 \ \ / / O Mo O //\\ H5C6-N2 N2-C6H5

(10-14)

CH3

2 HN(C2H5)3

10.35

10.36

The second example (Kang et al., 1989) is the reaction of an octaoxomolybdenum complex (10.37) with phenylhydrazine and with 1,1-dialkylhydrazines. Although the latter hydrazine reactions are not within the scope of this section, but do belong to Section 10.3, we mention it here in order to demonstrate that an apparently small change in the hydrazine structure may lead to completely different diazenido complexes: with phenylhydrazine, the complex 10.39, a tetranuclear product with four diazenido groups, is formed. With dialkylhydrazines, however, an octanuclear complex (10.38) with six diazenido groups was found (Scheme 10-15)!* Insertion reactions of arenediazonium ions into metal-carbon bonds are rather rare. Legzdins et al. (1989) found the chromium complex 10.40 with a methyl(aryl)diazene ligand in the reaction of [Cr(C5H5)(NO)2(CH3)] with 4-nitrobenzenediazonium tetrafluoroborate. * The nitrogen-containing ligands in 10.36 and 10.39 may be viewed as diazenido or as hydrazido(3 -) ligands, respectively. We leave this question open. This discussion leads too far into structural organometallic chemistry and need not be discussed for these specific compounds.

436

10 Metal Complexes of Diazonium and Diazo Compounds in 5

s s

uu x% <

£ =1*

0,0 I

O 0> O/'\

°xx//0 1— /\ 0)

/ \S c/ ' °^ i=0

-

A X/N\

0/X0

"^,-Q

-

S

10.2 Synthesis of Aryldiazenido Metal Complexes

437

N O

As palladium catalysts play a significant role in various synthetic methods based on the dediazoniation of arenediazonium salts (see Zollinger, 1994, Sects. 12.8 and 12.9), we discuss in the following two investigations on the interaction of palladium complexes with diazonium ions. No (aryldiazenido)palladium complexes were reported in the literature, until Rattray and Sutton (1978) found that the complex [Pd2(dppm)2Cl2] [dppm = (C6H5)2PCH2P(C6H5)2; 10.41] reacts smoothly with various substituted benzenediazonium tetrafluoroborates (10-16) in acetone without dediazoniation to yield 1:1 complexes of the type [Pd2(dppm)2(N2-Ar)Cl2] + BF,j~ (10.42) *. Previously, it was found (Olmstead et al., 1977) that the complex 10.41 adds CO or isocyanides (RNC) by insertion of these ligands in a bridging position between the two Pd atoms. The NMR spectra of the diazenido complex 10.42 reveal that the four P atoms are still equivalent and the AA'BB' spectrum of Ar is consistent with a bridging ligand. More recently, structure 10.42 was corroborated by an X-ray investigation of the analogous platinum complex (Neve et al., 1992). CH2

CH2

(C6H5)2PX

/

(CflH5»2P

+

Cl— Pd — Pd— Cl

hArN2 BF4-

X

P(C6H5)2

\ A / Cl— Pd II Pd— Cl

CH2

CH2

10.41

10.42

(10-16)

Rattray and Sutton's binuclear complex 10.42 contains Pd^atoms. Palladium(O) complexes resulted, however, in spontaneous elimination of N2 to give arylpalladium complexes (Kikukawa and Matsuda, 1977; Rattray and Sutton, 1978). Yet, Matsuda's group (Yamashita et al., 1980) was able to obtain (aryldiazenido)palladium(O) complexes by adding two equivalents of an arenediazonium tetrafluoroborate or hexafluorophosphate to a suspension of [[P(C6H5)3)4Pd°] in dichloromethane at — 78°C and allowing the mixture to warm to room temperature. Scheme (10-17) demonstrates that a mixture of the aryldiazenido and the aryl complex of Pd is formed. The aryldiazenido complex is subject to dediazoniation at room temperature. UV-irradiation facilitates this dediazoniation. Only in the case of 4-methoxybenzenediazonium hexafluorophosphate was it possible to isolate the aryldiazenido complex and to identify it by elemental analysis, 1H NMR, and IR spectroscopy. * Binuclear complexes of this type of structure are called A-frame complexes (see Sect. 10.3).

438

10 Metal Complexes of Diazonium and Diazo Compounds 4 ArN2+ X- +

[{(C6H5)3P}4Pd]

[(ArN2)Pd{P(C6H5)3}3]+ X- + [ArPd{P(C6H5)3}3]+ X~ + [ArN2P(C6H5)3]+ X- + [ArP(C6H5)3]+X-

An interesting reaction may also be mentioned in this section, although it does not lead to an aryldiazenido complex. It is known that transition metal alkynilide complexes [M(Ca = CpR)(Ln)] can be protonated and alkylated at the C(/?)-atom (review: Bruce and Swincer, 1983). This is consistent with theoretical findings that electron density in the HOMO is localized on this C-atom (Kostic and Fenske, 1982). Bruce et al. (1987) found that this type of reaction takes place with arenediazonium salts as electrophiles. Addition of seven arenediazonium hexafluorophosphates to an equimolar amount of [Ru(C = CR)[P(C6H5)3)2(r|5-C5H5)] in diethyl ether or tetrahydrofuran led to complexes of type 10.43 in good yield. Analogous compounds were found with the corresponding (alkynilide)osmium complex.

RU-C

/R

= C

PF

6

R =

/ \ N=N (C6H5)3P P(C6H5)3 \

10.43

In the next section, we will discuss several alkyldiazenido complexes which were obtained by alkylation of dinitrogen complexes with strongly nucleophilic alkylation reagents. At least one such case is also known for aryldiazenido complexes. Sellmann and Weiss (1978) showed that a (dinitrogen)manganese complex reacts with phenyllithium (see Sect. 3.3). Zinc is considered to be a borderline transition metal. ZnCl2 is used as an additive to arenediazonium chlorides because it increases the inertness ("kinetic stability") towards explosive dediazoniation. Three X-ray investigations of such socalled double salts (ArN^)2ZnCl4~ (see Zollinger, 1994, p. 24) reveal that the two diazonium ions are not coordinated to the metal atom (Mostad and R0mming, 1968). These compounds are not, therefore, complexes containing aryldiazenido ligands.

10.3 Diazoalkanes as Ligands in Transition Metal Complexes

439

10.3 Diazoalkanes as Ligands in Transition Metal Complexes By definition, the formation of a transition metal complex is based on coordination of one or more atoms of the ligands with the metal atom or ion. The ligand is an electron donor or, in other words, a nucleophile. In diazoalkanes the strongest nucleophilic centre is not the N(j6)-, but the C(a)-atom (see Sect. 4.4). Therefore, carbon coordination is more often observed and used synthetically than in complex formation with arenediazonium ions. In carbon coordination of diazoalkanes to transition metals, the diazo group is either still present, and such coordination products can be used as synthons like diazoalkanes themselves, or coordination with the metal leads to dediazoniation. For these reasons we have already discussed carbon coordination in Section 9.1. The present section concentrates on diazoalkane ligands in which coordination to the metal takes place through one or both diazo N-atoms, i.e., in analogous ways to those with aryldiazenido ligands (Sects. 10.1 and 10.2). The development of our knowledge of transition metal complexes with alkyldiazenido ligands is very different from the situation for aryldiazenido complexes discussed in the preceding two sections. There seem to be two reasons for that development. First, the direct interaction of diazoalkanes with transition-metal complexes more often results in dediazoniation or in coordination at the C(a)-atom (see above) and not in the straightforward addition or in the substitution of a ligand by the diazo compound. The second reason is the greater variety of synthetic methods for the preparation of (relatively) stable metal complexes with alkyldiazenido ligands. This variety did not lead, however, at least until today, to a larger number of structurally well characterized alkyldiazenido complexes relative to the aryldiazenido complexes. For these reasons, we start this section not with a discussion of structural types of alkyldiazenido complexes, but with the syntheses. Here, it is remarkable, that, in two early reviews and in three specific papers published in the 1970's and 1980's, the first synthesis of alkyldiazenido complexes was claimed in various papers published in 1967, 1969, 1972, 1978, and in the mid-1980's. These uncertainties are, in the opinion of the present author, related to the two reasons mentioned in the preceding paragraph. Our own literature search leads us to the conclusion that Niemeyer (1978) was correct when he quoted the two papers of Mill's group (Bagga et al., 1967; Baikie and Mills, 1967) as first descriptions of alkyldiazenido complexes. These authors found that in thermal reactions and under irradiation, both pentacarbonyliron and dodecacarbonyltriiron form mixtures of orange and black complexes with diaryldiazomethanes. X-Ray structure determination showed that the orange product obtained from pentacarbonyliron and di(/?-tolyl)diazomethane is a 2:2 complex (10.44, Bagga et al., 1967) and that the black product obtained from dodecacarbonyltriiron and diphenyldiazomethane is a 3 :2 complex (10.45, Baikie and Mills, 1967). It is surprising that the reactions lead to a mixture of two quite different products and, as indicated by their color, that they are structurally not the same, irrespec-

440

10 Metal Complexes of Diazonium and Diazo Compounds Ar

\>e3 cooc

r\i

10 44

'

10.45

tive of the type of the reaction (thermal or photochemical) and irrespective of the type of ironcarbonyl used *. We shall return to binuclear complexes later in this section. Lappert and Poland (1969) were the first authors who reported on the discovery and characterization of mononuclear alkyldiazenido complexes by reaction of (trimethylsilyl)diazomethane with tricarbonyl(cyclopentadienyl)molybdenum hydride and the analogous tungsten hydride. Scheme (10-18) demonstrates that these reactions are not simple substitutions of a carbonyl by a diazenido ligand, but that they are insertions of the diazoalkane into the M —H bond (see also Lappert and Lorberth, 1967). [Mo(CO)3(Tf-C5H5)H] + (CH3)3SiCH=N2

"CO

> [Mo(CO)2(n5-C5H5){N2CH2Si(CH3)3}]

(10-18)

Herrmann (1975 a) showed later that this reaction is not typical for the presence of the trimethylsilyl group only. It also occurs with diazomethane, diazoethane, and phenyldiazomethane. An X-ray structure analysis of the corresponding W complex (Hillhouse et al, 1979) revealed that the W-N p = Na and Np = N a -C angles are 173.3° and 116.5°, respectively. This result and the N=N bond length (121.5 pm) are consistent with an NN-double bond (10.46).

* The origin of the two hydrogens in 10.44 is not clear at all.

70.3 Diazoalkanes as Ligands in Transition Metal Complexes

441

A characteristic feature of complex 10.46 is the capability of adding electrophilic reagents at the N(a)-atom, e.g., other metal complexes (Hillhouse et al., 1983) or, with trifluoromethanesulfonic acid in ether, protons (Herrmann et al., 1984). A similar alkyldiazenido complex of manganese was obtained by Herrmann (1975 b) with diethyl diazomalonate (10-19), which replaces the THF ligand in the Mn complex (10.47). This diazenido complex is remarkably stable; the diazenido ligand can be exchanged for a carbonyl ligand with CO only under high pressure. By analogy with the IR spectra of comparable aryldiazenido complexes [M(Ti5-C5H5)(CO)2(N2Ar)], e.g., M = Mo (Carroll et al., 1974), it was originally assumed that the IR band at 1951 cm"1 corresponds to the NN stretching frequency, and that such a value indicates strong N = N triple bond character and, therefore, an N —N —C angle close to 180°, i.e., a dominant mesomeric structure 10.48 b. However, the X-ray based structure of a comparable iridium complex, also obtained by ligand exchange with 2,3,4,5-tetrachlorodiazocyclopentadiene by Schramm and Ibers (1978, 1980a, see 10.14 in Sect. 10.1), provides evidence for an N — N — C angle in 10.48 that is significantly smaller than 180° and for relatively little N = N triple bond character of this diazenido ligand.

N2C(COOC2H5)2

(10-19)

COOC2H5 10.48a

10.48b

C

°OC2H5

Ordinary diazoalkanes without strongly electron-withdrawing substituents, namely monoaryldiazomethanes, diphenyldiazomethane and a-phenyldiazoethane, were found by Hillhouse and Haymore (1982) to react with the tricarbonylbis(dimethyldithiocarbamato) complexes of tungsten and molybdenum [M(CO3[S2CN(CH3)2)2] at room temperature. The diazenido complexes, which were isolated in good yield, are very stable in an N2 atmosphere. Two carbonyl ligands were substituted by one diazoalkane: [M(CO)(N2CR'R")(S2CNR2)2]. NMR and IR spectra indicate that the diazoalkane ligand in these complexes behaves as a terminal, singly bent, four-electron donor ligand. Until today, it is a general rule that 1:1 adducts of diazoalkanes with transition metals are unstable in most cases. The stability can be significantly increased if dibenzoyldiazomethane is used as ligand. This was demonstrated by Cowie et al. (1986 a) in the synthesis of iridium complexes. As shown in (10-20), dibenzoyldiazomethane replaces the dinitrogen ligand in the starting material. The reaction is run

442

10 Metal Complexes of Diazonium and Diazo Compounds «rans-[lrCI(ISI2){P(C6H5)3}2] + (C6H5CO)2CN2

IrCI [^(COVtfcfPfCehysk] 10.49

\+ HO (1 eq)

IrCI [N^COCeHsMDlPfCeHsU;,] 10 50

-

(10-20) +

L = PfCH^CeHg), f-C4H9NC, NO

(C6H5)3P

(C6H5)3P

H

Ck. | .,,,N=N>X

O

Ck |

(C6H5)3P

c H5C/

10.52

10.51

under nitrogen in toluene suspension at room temperature. The color of the system changes rapidly from yellow to green. The green product precipitates completely on addition of hexane. The reagents are used in a 1:1 molar ratio, and the yield is 96%. The tetra-coordinated product 10.49 forms penta-coordinated complexes of type 10.50 by addition of dimethyl(phenyl)phosphine, tert-butyl isocyanide, and nitrosyl ion. On the basis of IR data and in analogy with the structure of the corresponding Ir complex containing a 2,3,4,5-tetrachlorodiazocyclopentadiene ligand (Schramm and Ibers, 1978, 1980a) instead of the dibenzoyldiazomethane, the structure of 10.49 is likely to be that containing the intact diazoalkane ligand coordinated in an rj 1 , singly bent geometry (no detailed data given). Most interesting is the reaction with hydrochloric acid, added in a 1:1 ratio as the dimethylacetamide — HCI adduct, which is to be used in an extremely dry form. A 1:15 mixture of the compounds 10.51 and 10.52 is obtained. In contrast, Schramm and Ibers (1978, 1980 a) found that the reaction of the tetrachlorodiazocyclopentadiene complex [(lrC\(N2C5C\4)(P(C6U5)3}2] with HCI yielded only the species corresponding to structure 10.52. Cowie et al. (1986 a) characterized the compound 10.52 by an X-ray structure that corresponds to the octahedral metal complex shown, which explains the relatively high thermal stability of this compound. The stability is due to the dibenzoyldiazomethane ligand acting as bifunctional ligand through N(/?)- and through one of the benzoyl O-atoms or, in other words, to a chelate effect.

10.3 Diazoalkanes as Ligands in Transition Metal Complexes

443

The reaction with HC1 involves a reversible hydride transfer from the Ir- to the N(/?)-atom. This process is obviously a condition for the chelate formation. In a subsequent paper, Cowie et al. (1986 b) reported on the formation of interesting and unexpected products obtained from this chelate complex 10.52. When the latter was refluxed in toluene, dediazoniation and ortho metalation of one of the phosphine groups took place leading to the /?-diketonate complex shown in Fig. 10-1. The diketonate group chelates through both O-atoms and is formed by hydride transfer from the metal to the carbene C-atom that is generated by the dediazoniation.

Fig. 10-1. Perspective view of the dediazoniation product of the Ir-complex 10.52 (with 20% thermal ellipsoids, after Cowie et al., 1986 b).

An interesting, related reaction also giving a chelated complex was found much earlier by Green and Sanders (1967). In the reaction of the anionic complex [Mo(C5H5)(CO)3]- with ethyl diazoacetate (N2CHCOOC2H5) followed by protonation they isolated the complex 10.53, the structure of which was established by an X-ray investigation of Knox and Prout (1969). It is interesting to observe that, for the formation of the six-membered hydrogen-bonded ring one of the carbonyl ligands of the reacting Mo complex is involved. In the similar reaction of dicarbonyl(TJ 5-cyclopentadienyl)(tetrahydrofuran)manganese with ethyl diazomalonate no fivemembered ring was detected in the X-ray structure. The Mn —N —N angle is 176.9°, the N-N-C angle 150.5° (Herrmann et al., 1981). Another type of end-on addition product of diazoalkanes to metal complexes was found by the group of Schwartz (Smegal et al., 1986). They used oxomolybdenumbis(alkylamino-dithio-carbamates) [MoO(S2CNR2)2], R = CH3 or C2H5, which are prepared from readily available disodium molybdate

444

10 Metal Complexes of Diazonium and Diazo Compounds

C

CO

^ ^N CO H 10.53

(Na2MoO2 • 2H2O) and sodium methylamino- or ethylamino-dithiocarbamate. In THF, the Mo compound is treated with various simple diazoalkanes, e.g., phenyl-, diphenyl-, methylphenyl-, and secondary alkyl-diazomethanes. In this reaction (10-21), metalloazines of type 10.54 are formed as yellow crystals in a broad spectrum of yields up to 99%. The ratio of (Z)- to (E)-isomers was determined based on 13C NMR spectroscopy. These metalloazines behave as active carbonyl equivalents in a Wittig-type reaction with phosphoranes (10-22) and form the corresponding ethene derivatives.

/R3

OMo(NN=CR1 R2)(S2CNR2)2

+

(C6H5)3P=C

V

(10-22) /R3

:

+ Ng + OMo(S2CNR2)2

+ P(C6H5)3

V

In Section 10.2, Sutton (1993) was quoted because all attempts to synthesize aryldiazenido complexes of nickel were without success. Nevertheless, alkyldiazenido complexes are known, as seen below. Some alkyldiazenido complexes of nickel, palladium, molybdenum, and ruthenium were obtained by ligand exchange or by ligand addition. They were later demonstrated not to have end-on structures, but a side-on (n2) coordination at both diazo N-atoms. Itsuka and coworkers demonstrated that in bis(tert-butylisocyanide)

10.3 Diazoalkanes as Ligands in Transition Metal Complexes

445

complexes of nickel and palladium a ligand can be exchanged by diphenyldiazomethane [M(Y-BuNC)2(N2C(C6H5)2)] and by diazofluorene [M(J-BuNC)(N2C13H8)] (Otsuka et al., 1972, 1975; Yarrow et al., 1973). Analogous products were obtained by these authors with triphenylphosphine complexes of Ni and Pd. Similarly, a (TJ 5-cyclopentadienyl)molybdenum complex with diazofluorene was synthesized by the same group (Nakamura et al., 1974). The main evidence for the side-on coordination was delivered by the X-ray structure analyses of [Ni(f-BuNC)(N2C13H8)] (Nakamura et al., 1977) and of [Ru(CO)2(N2C5Cl4)[P(C6H5)3]2] (Schramm and Ibers, 1980c; 10.56). Based on that information, the structure is best described by a hybrid of structures 10.55 a and 10.55 b. A common feature of these structures is that the diazoalkane is an T|2-7t-bound, two-electron donor. 1ST

M—||

N+

-*

CAr2 10.55a

^

N+ M —|| N

CAr2 10.55b

P(C6H5)3 °C',,, OC^

69.5<^N

P(C6H5)3 10.56

In addition to the (diazenido)ruthenium complex 10.56, Schramm and Ibers (1980b) also investigated the complex obtained by reaction of [IrCl(N2)[P(C6H5)3]2] with 2,7-dibromo-9-diazofluorene in the presence of ethanol. They obtained a compound of the composition [IrHCl(2,7-Br2N2C13H6)[P(C6H5)3]2]. The *H NMR spectrum exhibits a 1:2:1 triplet (2J = 14.7 Hz) at 8 = -26.93, indicating a hydride ligand coupled to two equivalent phosphorus nuclei. A very strong IR band at 2224 cm"1 may be assigned to an Ir —H bond. In analogy to known orthometalated aryldiazenido complexes of iridium (Gilchrist and Sutton, 1977; Cobbledick et al., 1977), Schramm and Ibers assume that a possible structure for their compound is the ortho-metalated hydrido complex 10.57. No X-ray investigation of this complex was attempted, unfortunately, because it seems to the present author that the (Z)-configuration of the azo bridge is rather doubtful. In all these reactions of chloroiridium complexes no insertion into the Ir — Cl bond was observed. For chloroplatinum(n) complexes, however, such insertions have been observed. McCrindle and McAlees (1993) investigated the reaction of the dichloro(l,5-cyclooctadiene)platinum complex with three monosubstituted diazo-

446

10 Metal Complexes of Diazonium and Diazo Compounds .Br

10.57

methanes and found a step-wise insertion into both Pt — Cl bonds. This significant difference between Pt - Cl and Ir - Cl bonds is remarkable. These two metals are in the same period of the Periodic Table and within directly neigboring groups (see Table 10-1 in Sect. 10.1). A very interesting synthetic approach to alkyldiazenido complexes was discovered by Chatt et al. (1972) in the context of their work on dinitrogen as ligand in transition metal complexes. They found that in the reaction of dinitrogen complexes of molybdenum and tungsten with acid halides, (acyldiazenido)- and (aryldiazenido)chloro complexes were formed (10-23). Later, Chatt's group (Diamantis et al., 1975; Ben-Shoshan et al., 1976; Chatt et al., 1977a; Bevan et al., 1977) as well as George and coworkers (Day et al., 1975; Busby and George, 1976) realized that this type of diazenido complex synthesis works not only with acyl halides, but also with alkyl halides (10-24) and with gew-dibromides (10-25) under tungsten-filament irradiation (Ben-Shoshan et al., 1980). [M(N2)2(dppe)2] + RCOCI

[M(N2)2(dppe)2] + RX

*-

^->-

[MCI(N2COR)(dppe)2]

(10-23)

[MX(N2R)(dppe)2]

(10-24)

[wBr(N2CRR')(dppe)2]+ Br

(10-25)

-N2

[W(N2)2(dppe)2] + Br2CRR'

^-^

R = alkyl or aryl M = Mo or W dppe = 1,2-bis(diphenylphosphino)ethane

An interesting approach to another group of diazenido complexes by the use of dinitrogen complexes was found by Hidai's group (Watakabe et al., 1983; Hidai et al., 1986) in the reaction of cw-[W(N2)2[P(C6H5)3)4] and cis[W(N2)2[(C6H5)2PCH2CH2P(C6H5)2]2] with acetylacetone (10-26). In this reaction, ketazines are not formed, but complexes with an alkenyldiazenido ligand and an acetylacetonate chelate ligand (e. g., 10.58) are. It is likely that the first step is addition of one or two protons from acetylacetone to the N(/?)-atom. Dinitrogen metal complexes can also be silylated at the N(/?)-atom by treatment with suitable trialkylsilane derivatives. Such reactions were also investigated by

10.3 Diazoalkanes as Ligands in Transition Metal Complexes

447

O

(10-26) CH3

O

- P(C6H5)3 °LJ° = acetylacetone 10.58

Hidai's group (Hidai et al., 1984; Komori et al., 1989a and 1989b). In the 1984 and 1989 a papers, they described the use of trimethyliodo-, -bromo- and -chlorosilane for the silylation of tungsten and molybdenum complexes, e. g. , for the formation of ^«5-[WI[NNSi(CH3)3)[P(CH3)2(C6H5)]4] from c/s-[W(N2)2[P(CH3)2(C6H5)]4], and in the 1989 b paper trimethylsilyltriflate (Me3SiOSO2CF3). The second reaction works more smoothly. An interesting observation was made when the iodo(trimethylsilyldiazenido) molybdenum and tungsten complexes were treated with metallic sodium sand in THF under argon: bis(trimethylsilyl)amine and ammonia were produced in substantial yield accompanied by the formation of free dinitrogen, the starting dinitrogen metal complex, and sodium amide (10-27). If the reaction was carried out under N2, the dinitrogen complex was formed in higher yield (Komori et al., 1989 a). A more detailed investigation of that process is recommended.

[M(N2)2{P(CH3)2C6H5}4] + (CH3)3Sil ^^^

[Ml{NNSi(CH3)3}{P(CH3)2C6H5}4] + Na

in THF

(1 0-27)

HN{Si(CH3)3}2 + N2 + NaNH2 + NH3

Another synthesis of alkyldiazenido complexes is due to Chatt et al. (1977 b), and independently to the work of Hidai et al. (1976 b), namely a route by condensation of hydrazido(2 —) metal complexes with aldehydes or ketones. The original work of Hidai et al. (1976 a) concentrated on molybdenum complexes, that of Chatt et al. (1977 b) on tungsten, but both groups used the same type of ligands as their starting material complexes, namely [Mo(NNH2)(dppe)2]+X~ (X = F, Cl, Br or I)*. The dppe = l,2-bis(diphenylphosphino)ethane.

448

10 Metal Complexes of Diazonium and Diazo Compounds

hydrazido(2-) complexes of Mo and W can be obtained by treatment of the corresponding dinitrogen complexes with tetrafluoroboric acid in THF (Hidai et al., 1976a; Chatt et al., 1976, 1977c) in good yield (10-28). Structure analysis of the hydrazido(2-)molybdenum complex (10.59) demonstrated that the Mo-N-N linkage is essentially linear, that the N —N —C angle is 125°, and that two hydrogen atoms are attached to the N(/?)-atom (Hidai et al., 1976a, 1978). Complex 10.59 readily condenses with a variety of aldehydes and ketones in dichloromethane to afford a new kind of diazenido ligand, namely the hydrazone-type ligand in complex 10.60 in good yield (10-29). The brown to green salts are fairly stable in air. ™F >

M(N2)(dppe)2 + 2 HBF4

[MF(NNH2)(dppe)2] + BF4~

+ BF3 • THF

(10-28)

10.59

In a joint paper of Chatt's and Hidai's groups (Bevan et al., 1978), it is shown that hydrazido(2-) complexes of tungsten that contain mono(tertiary)phosphines [WX2(NNH2)(PR3)3] (X = Cl, Br, I) can easily be obtained from the dinitrogen complexes with hydrogen halides (HX). Further protonation to yield hydrazido(l—) complexes has also been achieved and compounds such as [WCl3(NHNH2)[P(CH3)2(C6H5))3] have been isolated. The reaction of the hydrazido(2 —) complexes with ketones follows in principle reaction (10-29), but leads to neutral complexes like 10.61 (X = F, Cl, Br, I). The IR and the *H and 13 C NMR spectra indicate meridional phosphine ligands and the azine-like bonding of the N-atoms to W- and C-atoms (see also Mizobe et al., 1980). These complexes can be deprotonated at one of the alkyl groups R or R7 to the corresponding alkenyldiazenido complexes, e.g., to 10.62 (if R = R' in 10.61). Lithium di(2-propyl)amide or sodium bis(trimethylsilyl)amide is used as reagent (Ishii et al., 1990, 1992).

10.59 + R'R"C = O

CH2CI

*-

[MF(N—N=CR'R")(dppe)2] + BF4~

+ H2O

(10-29)

10.60

Complexes of type 10.61 can also be converted into isocyanide complexes (one X in 10.61 = C=N —^-C 4 H 9 ) which, after reaction, first with A1(CH3)3 and second with trimethyloxonium salt (Meerwein reagent) and CO, yield, e.g., the alkyldiazenidoaminocarbene complex 10.63 (Harada et al., 1994). If the substituents R or R' in the complexes 10.61 and 10.64 contain an a-CH group (10-30), the latter can be deprotonated in benzene suspension with lithium diisopropylamide (LDA) and the resulting alkenyldiazenido complex (10.65) can be acylated with isocyanates, isothiocyanate, or diphenylketene to give regiospecifically a-acylated and a-diacylated diazoalkane complexes (10.66 and 10.67) after reprotonation (Miyagi et al., 1991). Diazoalkane complexes of type 10.64 can be methylated or phenylated at the CH2R" group by lithium dimethyl- or

10.3 Diazoalkanes as Ligands in Transition Metal Complexes

R \

CH2 II C

R

// ~ '

C6H5

A,

1ST

1ST

^

H/X

N

449

v

\\\y-j/ oc—w=c r^<\ \ N—CpHgJg ^r;^

C6H5(CH3)2P-W-P(CH3)2C6H5 /

P ^

C6H5(CH3)2P' Y

p v^

H 10.61

10.62 10.63 ©

CHgR"

CHR"

= P(CH3)2C6H5

CHRXONHR

CR/r(CONHR)2

rp-H-p^ A^ Vp^

|

^D/

F 10.64

10.65

10.66

10.67

, f P = (C6H5)2PCH2CH2P(C6H5)2 or {P(CH3)2C6H5}2

(10-30)

R = C6H5, 4-CH3C6H4, 1-C10H7, f-C4H9 R' = H, CH3 R" = H, CH3

diphenylcuprate (LiCuR2), respectively, as shown by Hidai's group (Seino et al., 1994). An X-ray structure analysis of the complex 10.67 (R = C6H5, R' = CH3, R" = H) revealed that the W - N - N angle is 170.4° and the N - N - C angle is 122.1°, i.e., similar to those of the starting material (10.64). The hydrazidometal(l-) complex [WCl3(NHNH2)(PMe2Ph)3] mentioned above condenses with acetone to yield an (alkylidene)hydrazido(l —) metal complex [WCl3(NHN = CMe2)(PMe2Ph)3] (Bevan et al., 1978). In the context of the formation of metal complexes with dialkyl diazenido groups from the corresponding complexes with dialkylhydrazido(2 —) ligands, it is interesting to refer to the reverse reaction. Chatt's group (Diamantis et al., 1977; Chatt et al., 1980) found that organodiazenido complexes of the type [MX(NNR)(diphos)2] with M = Mo or W, R = alkyl, X = Br or I, diphos = (C2H5)2PCH2CH2P(C2H5)2 or Ar2PCH2CH2PAr2 react in THF with alkyl bromides (R;X') or iodides to give dialkylhydrazidometal(2-) derivatives [MBr(NNRR/)(diphos)2]+ X/ ~.

450

10 Metal Complexes of Diazonium and Diazo Compounds

In this type of reaction nucleophilicity of the diazenido group was investigated for some series of Mo and W complexes in which the diphosphine ligands had 4-substituted aryl groups (10-31) with Y = CF3, Cl, H, CH3 and CH3O, i.e., a series of substituents with increasing nucleophilicity (Hussain et al., 1986). frans-[MBr(NpNaC2H5)(Ar2PCH2CH2PAr2)2]

+ CH3I (1

I trans- [MBr(NpNaCH3C2H5)(Ar2PCH2CH2PAr2)2]+

°~31)

l~

Ar = 4-Y-C6H4

Tungsten complexes react about an order of magnitude faster than their molybdenum counterparts. The influence of the aryl substituents is greater for the tungsten compounds. The electronic influence of the substituents on the nucleophilicity at the N(a)-atom is essentially inductive, as shown by the correlation versus Hammett's ap and a +: the correlation coefficient for ap is better (r = 0.97) than that for a+ (r = 0.92). The relatively large reaction constant (p = -0.6 per aryl substituent) clearly indicates, however, that the efficiency of the substituent on the aryl group in transmitting the effects is quite large. We have already mentioned earlier in this section that the first stable alkyldiazenido complexes described in the literature in the 1960's were di- and trinuclear complexes. Since then it was shown that diazoalkanes can coordinate to more than one metal atom in a variety of bridging modes. In 1980, Messerle and Curtis reported the reaction of tetracarbonyldi(cyclopentadienyl)dimolybdenum (10.68) with diaryldiazomethanes, resulting in the formation of air-stable green monoalkyldiazenido adducts, in which the terminal diazo nitrogen bridges the two Mo-atoms (10.69 in 10-32). At higher temperatures, dediazoniation to 10.70 takes place. Herrmann's group (Bell et al., 1982; Herrmann et al., 1983; Herrmann and Ihl, 1983) as well as Curtis et al. (1986) reported on similar reactions that result in more complex products. These authors investigated the reactions of molybdenum- and tungsten-containing carbonyl and pentamethylcyclopentadienyl ligands with dialkyldiazomethanes in which the diazo ligands were found to be bonded at both N-atoms and to be asymmetrical, as shown in 10.71. The thermal reactions of the diazenido complexes 10.69 and 10.71 are completely different from one another. Messerle and Curtis' complex undergoes a simple dediazoniation. The //-diarylcarbene formed as (unidentified) intermediate acts as a bidentate ligand to the rest of the binuclear molybdenum complex and forms 10.70. In the case of Herrmann's complex, however, a symmetrically bridged imine ligand is formed and the other nitrogen atom undergoes insertion into an M — CO bond to form a terminal isocyanate ligand (10.72). By the reversible addition of carbon monoxide to 10.72 the complex 10.73 was formed. This equilibrium is a good evidence for a Mo = Mo double bond in 10.72. All structures in reaction sequence (10-33) have been established by X-ray analyses. Analogous reactions were found with the corresponding tungsten complex (Herrmann and Ihl, 1983).

10.3 Diazoalkanes as Ligands in Transition Metal Complexes OC

451

CO

Cp-Mo = Mo-Cp

OC

+ Ar2CN2

CO 10.68 25°C

Cp = Ti5-C5H5

Cp-Mo

OC

Mo-Cp

CO OC

(10-32)

CO

10.69 60°C

- N2

Cp(CO)2Mo -

Mo(CO)2Cp

10.70

CH3

* = CH3 I (10-33)

h CO (0°C) -CO (AT)

Earlier, Herrmann et al. (1976 a, 1976 b) found that the mononuclear (pentacarbonyl)(hydrido)manganese complex 10.74 forms a 10 : 1 mixture of the di- and trinuclear complexes 10.75 and 10.76 with diazomethane, if the reagents are mixed in THF at — 85 °C and the system is allowed to reach room temperature (10-34). In the same reaction with the analogous rhenium complex, only the binuclear complex

452

10 Metal Complexes of Diazonium and Diazo Compounds (CO)5MnNH + CH2N2 10.74

-H 2 ) -CO -^°to25°C (10-34)

\j

OC

PO II pnCO | C I , Mri"N ^'N-Mh-CO

OP^ I

SI

NT

H

(CO)4Mn/

H

-Mn(CO)4 N=NN

10.76

10.75

corresponding to 10.75 was found. With analogous hydridocarbonyl molybdenum and tungsten complexes, mixtures of mono- and binuclear products were found in the reaction with diazoalkanes (Herrmann and Biersack, 1977). An example for the introduction of a diazoalkane ligand into a cluster complex built from three osmium atoms with nine CO molecules and one diphenylacetylene (10.77) was described by Shapley's group (Clauss et al., 1981). The reaction yields almost equal amounts of a thermally stable //-diazomethane adduct (10.78) and a //methylene complex (10.79; 10-35). This dediazoniation product can also be obtained from the //-diazomethane adduct 10.78 by irradiation. An X-ray structure of a related Os complex was published more recently by Day et al. (1992).

\

/C6H5

(10-35)*

10.77

10.78

10.79

Woodcock and Eisenberg (1985 b) described an interesting insertion product of ethyl diazoacetate and diethyl diazomalonate (10.81, R=H, R' = COOC2H5, and R=R' = COOC2H5, respectively) between the two rhodium atoms of the complex 10.80 under reductive elimination of H2 (10-36). This type of tricyclic structure is called an A-frame (see also 10.42 in Sect. 10.2). Evidence for this structure is provided by IR, *H and 31P NMR spectra, which are consistent with A frame compounds that were analyzed earlier by these authors (Woodcock and Eisenberg, 1984, 1985a; Kubiak et al., 1982). These complexes do not undergo elimination of N2 either thermally or photolytically to form the corresponding //-alkylidene complexes, * All three complexes contain three carbonyl ligands at each of the osmium atoms (Clauss et al., 1981).

10.3 Diazoalkanes as Ligands in Transition Metal Complexes

453

N2CRR

'

10.80

10.81

(C6H5)2

nor do the diazoalkane ligands undergo NN bond cleavage. In these two respects, they are clearly different from the complexes studied by Herrmann et al. (1983) and by Clauss et al. (1981) that we discussed before. Some Wnuclear metal complexes containing a silyldiazenido ligand and two different metal centers were synthesized by Street et al. (1991) in Hidai's group. They showed that the trisubstituted silyl ligands of tetracarbonyl(silyl)cobalt complexes 10.83 were transferred to the dinitrogen ligands of molybdenum and tungsten complexes of type 10.82 to give silyldiazenido complexes 10.84, in which one of the carbonyl groups acts as a bridging ligand between the two metal atoms (10-37). In benzene, yields of 35-90%, depending on ligand [P(C6H5)3 or (C6H5)2PCH2CH2P(C6H5)2], metal (W or Mo), and substituents on silicon (CH3 or C6H5), can be obtained at room temperature, but only under rigorously dry conditions. The structure of the Mo complex was determined by an X-ray investigation to be octahedral around the Mo atom. The silyldiazenido and the (bridging) //-carbonyl ligands mutually occupy the trans positions. The Mo - N - N bonds are almost linear (177.1 °) and the N - N - Si bonds enclose an angle of 152.2°. The NN and NSi bond lengths of 121 pm and 173 pm, respectively, indicate bond orders between one and two. The four carbonyl ligands are arranged tetrahedrally around the cobalt atom. These complexes can be converted to silylhydrazidometal(2-) complexes with H2O, CH3OH, or HBr. [M(N2)(P)4] + [R2R'SiCo(CO)4] 10.82

10.83

(10-37) frans-[M(NNSi FyV)(P)4] [Oi-OC)Co(CO)3] 10.84

M = W, Mo P = phosphines (see text) R, R' = CH3 and C6H5 or C6H5 and CH3

454

10 Metal Complexes of Diazonium and Diazo Compounds

The nonspecialist reader of this section may come to the conclusion that the area of transition-metal complexes with alkyldiazenido ligands is not very large. This impression is reinforced by the fact that these complexes lose the diazo group relatively easily, as mentioned in the beginning of the section. It is wrong, however, if one considers the fact that diazoalkanes have been used, and still are, extensively in the preparation of carbenes via metastable diazenido intermediates of metal-complex catalysts in laboratory scale syntheses, in the Fischer-Tropsch reaction, and in olefin metathesis (see, e.g., Herrmann, 1978; Doyle 1986a, 1986b; and Sects. 8.7 and 8.8 of this book). We add to this section a few remarks on the reaction of diazoalkanes with transition metal atoms that are not complexed. Margrave, Billups and their coworkers (Chang et al., 1988) investigated the reactions of iron atoms that were vaporized in a resistant tantalum furnace over the range 1300-1500 °C. The iron atoms and diazomethane were condensed on a Cu surface with argon or dinitrogen at 11-14 K. Products were determined with a Fourier-transform IR spectrometer. The two major products are FeCH2 and N2FeCH2. The latter seems to be the product of insertion of Fe atoms into the N = C bond of diazomethane. The same authors investigated the analogous reactions of copper with diazomethane (Chang et al., 1987).

11 Epilogue: From Peter Griess' Discovery to Organometallic Diazo Compounds

We started volume I of Diazo Chemistry with the discovery of the first isolated diazo compound by Griess (1858). We ended the second volume with metal complexes containing diazo ligands. The purpose of this short epilogue is not to give a summary of the work carried out on diazo chemistry during the intervening 137 years, but to show that the development of knowledge in diazo chemistry is a fine example of the way by which, I think, chemists developed their part of science after the pioneering era, which began with Lavoisier's introduction of material balance in chemical reactions (1787) and ended with the discovery of the Periodic System of elements by Mendelejev in 1869. The subtitles of the two volumes indicate that we divided the subject into five groups, i.e., aromatic, heteroaromatic, aliphatic, inorganic, and organometallic diazo compounds. The three purely organic groups are clearly dominant — this is not surprising because diazo chemistry is considered to be part of organic chemistry. The fact that more space is used for aromatic than for aliphatic diazo compounds is, however, not consistent with organic chemistry in general. The reason is not only the earlier discovery of the first diazo derivatives of aromatic hydrocarbons (1858) than of aliphatic compounds (Curtius, 1883), but the much greater interest of the chemical industry in aromatic diazo chemistry: Since the 1860's, azo dyes were produced (see Travis, 1993, p. 214); their share of the total production of organic colorants is at present about 50%, and this percentage is even slowly increasing. The incessant activities in aromatic diazo chemistry also become evident from the literature on the synthesis of these compounds. A comparative overview of Chapters 2 in volumes I and II demonstrates that there are more relatively old, but optimized, procedures available for aromatic than for aliphatic compounds. Similar statements hold for papers on mechanisms of syntheses and on applications of reagents. Yet, it is surprising that for the metal-catalyzed diazo process, the Sandmeyer reaction (1884), a convincing and well-documented mechanism was found only one hundred years later (see Vol. I, p. 232 f.). On the other hand, the detailed elucidation of the mechanism of electrophilic aromatic substitution (nitration, halogenation, sulfonation, etc.) is based mainly on investigations of the azo coupling reactions in the 1950's (see Vol. I, Sects. 12.7-12.8). In general, empirical synthetic applications of arenediazonium salts have always been considerably ahead of an understanding of the reaction. In aliphatic chemistry, the situation is, in some areas at least, different. The most impressive example is Huisgen's review (1955) on the chemistry of diazoalkanes and, as a consequence, his discovery of the framework of 1,3-dipolar cycloadditions, which, after 1960, became very fruitful for diazoalkanes and many other 1,3-dipoles. Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

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11 Epilogue: From Peter Griess* Discovery to Organometallic Diazo Compounds

As briefly mentioned in Section 8.7 (p. 361) in 1992 we made an enquiry into large scale use of diazoalkanes. In production of the six largest manufacturers asked worldwide none used simple diazoalkanes such as diazomethane because of the volatility of such toxic compounds, which, in addition, are also explosive. Although aromatic diazo compounds are not harmless, they can be more easily handled (see, however, Vol. I, ps. 19, 22, 72). Organometallic chemistry started some forty years ago and developed rapidly, particularly that part involving transition metals. This can be illustrated by the facts that, in the period 1981-1992, not less than 1319 stable Organometallic compounds containing rhodium, a relatively rare member of the platinum group, were described (Sharp, 1995), or that stable complexes containing diazenido ligands with at least 19 transition metals are known (Sutton, 1993). On the other hand, no aryldiazenido complex of copper has been described, in spite of the fact that such coordination compounds may be formed in the Sandmeyer, Pschorr, and Meerwein reactions. The latter have been known, in part, for more than a century! We are aware, of course, that the search for the structure of catalysts is methodically very different from that for stable compounds. This is likely to be the reason that in the majority of review papers either structures of stable compounds or catalysts are discussed but correlations between these areas of interest are not *. Organometallic chemistry is defined as the chemistry of compounds with at least one carbon-metal bond. This is understandable for historical reasons. It is, however, unfortunate that a number of authors call ligands that form metal-heteroatom bonds "spectator ligands". Their role is far from that of being mere spectators. As discussed in Section 3.3, the first complex with dinitrogen does not even contain a C — M bond (3.16) and, by definition, does not formally belong to organometallics! This example demonstrates that the classification of complexes as those with and those without a metal-carbon bond is artificial or even false. In metal complexes, the ligands are electron donors and the metal is the acceptor, i. e., a Lewis acid. Looking at diazo chemistry superficially one may get the impression that at least the diazonium ions and the (so-called) inert dinitrogen ** are not suitable as donors. This is not the case, as shown in Sections 3.3-3.4 and in Chapter 10, respectively. In spite of more than 400 coordination compounds with diazenido and dinitrogen-ligands, the number of these compounds is not yet sufficient for systematization. For amines and related N-compounds which have been used as ligands in many more cases, such an investigation was only recently conducted on a broad basis by Togni and Venanzi (1994). Therefore, the development of our knowledge of underlying principles of the chemistry of metal complexes with diazenido and dinitrogen ligands is analogous to that of aromatic and aliphatic diazo chemistry, in the sense that such a development takes decades. Might theoretical chemistry bring a significant contribution to our general knowledge of transition metal complexes with diazenido and dinitrogen ligands? It is likely that this will indeed be the case, but hardly in the near future. * A remarkable exception is Togni and Venanzi's review (1994) on nitrogen donors. ** For a short discussion of the inertness of N2, see the Interlude in Vol. I (Chapt. 9).

11 Epilogue: From Peter Griess' Discovery to Organometallic Diazo Compounds

457

This question brings us back to purely organic and inorganic diazo chemistry. We consider, as indicated already in Section 5.3, the results on electron density distributions in ten organic and inorganic diazonium ions obtained by Glaser et al. (1992 b) as a major contribution to our knowledge on the structure of these ions. It was found in the series of compounds [XNN]+ that the positive charge is calculated to be located almost completely on the diazonio group (X = F), as expected for a diazonium ion in its classical formula X — N = N. The charge on X decreases almost continuously for other inorganic and organic diazonium ions (see Table 5-3) and becomes very small for the benzenediazonium ion. The dative bond description X<- N s= N, as proposed by Glaser et al. (1992b), therefore, has to be considered for any conclusions on structures, spectra, and reactivities of arene- and alkanediazonium ions. In the most recent part of their work, Glaser et al. (1995) compare the dative bond model of benzenediazonium ion with the calculated structures and binding energies of noble gas systems (C6H5-E) + . Also, in these cases, coordination of nobel gas atoms (E = He, Ne, and Ar) with the phenyl cation results in considerable stabilization (83, 97, and 94 kJ mol"1, respectively)*. As Glaser's results for ten diazonium ions clearly show that there are intermediate cases between the two extreme cases of positive charge locations, it is, in our opinion, impossible to use one of the two structures as "the" structure. The problem is analogous to that of mesomeric structures and even to tautomerism (e. g., the enol formula of a carbonyl compound is not written, even in cases where it is known that, say, the keto-enol equilibrium is 3:7!). Therefore, we still use the classical formula for all diazonium ions, except in cases where the dative bond model is important for the specific problem. Glaser's theoretical discovery that the charge distribution on diazonium ions varies from almost complete location on the residue X to location on the diazonio group will hopefully encourage an experimentalist to test product formation from diazonium ions with practically uncharged residues X, e. g., X = F: are the products consistent with reactions of fluorine atoms or fluoro cations? The analogous question is, of course, also open and worthwhile for the basic understanding of the diazonio functional group. It is the scientifically most important aspect of the inorganic diazonium ions. How reliable are numerical results of theoretical investigations? More and more sophistication in calculation methods improve their reliability — but they may become even better in the future! A recent case is the comparison of the dissociation energies of the methane- with the benzenediazonium ion in Glaser's work. In 1992, they were calculated to be practically identical, but in the most recent calculation (1995) the values of// diss were significantly different (176 and 122 kJ mol"1, respectively). A caveat is therefore appropriate for conclusions that reach too far. The experimental chemist would appreciate it if the authors of theoretical papers would indicate the reasons for which improved results arise. From my own experience at the time when experimental physical-organic evidence for the intermediacy of the phenyl cation in the dediazoniation of the benzenediazonium was increasing, I remember the honest statement of Castenmiller and Buck (1977) in their theoretical * For related coordination compounds of noble gases, see Bieske and Maier (1992).

458

11 Epilogue: From Peter Griess' Discovery to Organometallic Diazo Compounds

paper on the same problem: "Calculations of this kind of model appear to be beyond the scope of the present possibilities''. Another theoretician wrote to me in 1977 (with copies to other scientists) that the phenyl cation cannot be an intermediate because his published calculation resulted in a much higher activation energy to its formation. Theoretical work consistent with experimental data was published later by other scientists (see Vol. I, Sect. 8.4). Summarizing this epilogue, diazo chemistry demonstrates what is likely to be the most important characteristic of chemistry, namely that after any revolutionary discovery (in the sense of Kuhn, 1962), it is necessary to obtain broad experience with large numbers of related compounds and reactions (called normal science by Kuhn) in order to understand correlations of the discovery in a larger framework — a process that, in my opinion, is a primordial goal in scientific work.

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Index

Aceto-de-amination 415 l-Alkyl-3-aryltriazenes, see Triazenes (-)-Acetomycin 380 Alkyldiazenido ligands 3, 15, 113, 114, 115, Acrylic acid, (-)-menthol ester, as chiral 439 ff., 450 (nucleophilicity), 454 dipolarophile 237 Alkyldiazenoles and -olates 27, 128, 129, Acyldiazenido ligands 446 133, 245, 247ff., 250, 256, 257, 265f., /?-(Acyloxy)alkenediazonium salts 418ff. 268f., 279, 302, see also specific diazenols Alicyclic amines, deamination l-Alkyl-4,5-dihydro-l,2,3-triazoles, mechanisms 278 ff. mutagenicity 132 Alkanediazonium ions l-Alkyl-2-fluorodiaziridine 175 - dediazoniation 11 ff., 16, 20ff., 191, 302f. Alkyl group shifts 277, 298 - deprotonation 12 Alkylidenecarbenes 81 f., 326 - formation 244ff., 250, 251 f. Alkyl nitrites 245f., 301 - history 11, 12 JV-Alkyl-N-nitroso amides 17, 28ff., 246, - identification 2 247 - NMR data 145 A^-[(N-Alkyl-7V-nitrosoamino)methyl]benz- routes to, 244 ff. amide 31 f. - stability 11, 303 7V-Alkyl-7V-nitroso carbamates 2, 28ff., 33, - structure 145 ff. 246 - synthesis 12ff., 302 7V-Alkyl-7V-nitroso ureas, see Urea derivatives - theoretical investigations 161, 167ff., 457 Alkynediazonium ions - trapping by azo coupling 191 ff. - dediazoniation 172 [2 + 1] Alkene cyclodimerization 406 f. - identification 2, 92 Alkenediazenium ions 12ff., 145 - properties 92ff. Alkenediazonium ions . - syntheses 91 ff. - /?-(acyloxy)alkenediazonium ions 418ff. - theoretical investigations 169f., 172 - JV-azo coupling reactions 415, 416 Allenes, from diazoethene 82 - dediazoniation 194, 414 ff. Allyl cations 273 - deprotonation 160 Allyldiazonium ions, see 3-Propenediazonium - identification 2 ions - literature 10 Allyl-substituted diazoalkanes, intramolecular - reactions 415 ff. 1,3-dipolar cycloaddition 238 - rotamers 160f. Amides - spectroscopy 146 - nitrosation 123 f. - structure 160f., 169 - use as scavenger of HNO2 123f. - synthesis 83ff., 91, 160 Amidines 65f. - theoretical investigations 169ff., 171 f. a-Amino acids Alkenes - deamination 242, 296 f. - as dipolarophiles 212ff., 224ff., 229f. - fluoro-de-diazoniation 296 - reaction with carbenes 21 If., 318ff., /?-Amino alcohols, deamination 243 321 ff. 1,2- and 3,1-Aminobutenes, deamination a-(2'-Alkenylaryl)diazoalkanes 229 f. products 243 Alkenyl cations 417 f. cis- and tams-2-Amino-4-(teAt-butyl)cyclohexAlkenyldiazenido ligands 448 f. anols, deamination 300 Alkenylketenes 349 2-Aminobutylnitrile, deamination 271 Alkoxyalkenes, in dihydrofuran syntheses 1-Aminocyclopropanecarboxylic acid, 361 ff. diazotization 297 Alkoxydiazonium ions 252f., see also Amino-de-diazoniation 106 Methoxydiazonium ion Aminodiazonium ion 100, 169 Diazo Chemistry II: Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright © 1995 VCH Verlagsgesellschaft mbH ISBN: 3-527-29222-5

508

Index

Aminoisonitrile, comparison with CH2N2 174, 184ff. l-(Aminomethyl)-l-hydroxycycloalkanes, ring expansion by deamination 299 2-Amino-2-methylpropylnitrile, deamination 271 3-Amino-2-phenyl-l//-inden-l-one, nitrosation 83 f., 86 f. 9-Aminotriptycene-l,4-dione, deamination 191 Ammonia, reaction with nitrous acid 95 f. Anchimeric assistance 277 [4n + 2]Annulenes, reaction with :CH2 326 ff. Arenediazo anion 426 Arenediazonium ions - as ligands of metal complexes 421, 424 ff. - NMR data 151 - reaction with diazoalkanes 138, 234 - structure 457 Arndt-Eistert reaction 3, 16, 37, 345, 357 ff Aromaticity - of diazocyclopolyenes 164 f. - in dipolarophiles 205 2-Arylalkylamines, deamination products 243 277 Arylcarbenes 320 Aryldiazenido ligands 3, 111, 113, 114, 422 ff. Aryldiazenol esters 250 Aryl-a-diazo ketones 53 Aryldiazomethanes - acid-base equilibria 140 - spectroscopy 149ff. - syntheses 35, 36, 37, 39, 41, 44, 46 - see also Phenyldiazomethane, Diphenyldiazomethane a-(Aryliodonio)diazo compounds 392, 394 f. l-Aryl-3-methyl-2-diazo-l,3-diones, , t<^r rotamers 1-Aryl-l //-tetrazoles, formation in reactions /,. „ V, ,. . . of diazoalkanes with arenediazonium ions

, \ . . , ,.. . 1cr A Azotobacter vinelandu H5f. ,« 11^c^»r A Azoxysulfonates, solvolysis 252 f.

Asparagine, deamination 242 Aspartic acid, deamination 11, 242 Azaserine 23 f., 154 Azibenzil, see 2-Diazo-l,2-diphenylethan-l-one Azides, as 1,3-dipolar reagents 195, 198, 207, 208, 222 Azidinium salts, see Benzothiazolazidinium salts (Azido)(chloromethylidene)dimethylammonium chloride 61 2-Azido-3-ethylbenzothiazolium tetrafluoroborate 49, 57, 59ff., 136f. - see also Benzothiazolazidinium salts

Back-donation - general aspects 421 - interaction of carbenes with alkenes 323 - in metal complexes 110, 111, 425, 428, 429 Bader's theory of atoms in molecules 167, 168 ff. Balz- Schiemann reaction - of a cyclopropeniumdiazonium salt 93 f. - 2-diazo-l,3-dicarbonyl compounds 26 Bamford- Stevens reaction 23, 40ff., 315, 340

234

2-Azido-l-ethylpyridinium tetrafluoroborate 136f. 2-Azido-2-phenyl-l,l-dicyanoethene 62 (Azido)tris(diethylamino)phosphonium bromide 62 Azines, in reduction of diazo ketones 414 Azinopyridazines, as polarophiles 228 Aziridine, in polymethylene formation 173 Aziridin-1-yl imine derivative, as precursor of diazoalkane 235 f. Azo coupling reactions - of alkanediazonium ions with azide ion 194 - of alkanediazonium ions with C-coupling components 191 ff. ~ °f arenediazonium ions with diazoalkanes 138, 234 " °f aryldiazenido complexes 113 of ~ boranes 103 " competition with 1,3 -dipolar cycloaddition 193f - N-coupling 194 - P-coupling 194 ~ of diazoalkanes (as precursors of alkanediazonium ions) 192 f. ~ of 2-diazocyclohexan-l-one, -1,3-dione and °f heterocyclic diazo ketones 54, 57, 60 f. ~ in diazo transfer Processes 54, 57, 58 f., 60f 62 137 192 " > ' - "nucleophilic" lllf. - of quinone diazides 395 f. ~ thieno[3,2-£]thiophene as coupling c m n . . A ° P° ent ^ Azo-extrusion, see Dediazoniation Azolopyridazines, as dipolarophiles 28 oTm ° immeS' ^ 1>3"dlP°lar reagentS -A 1 ^ A- i ™ *^ l'*'*V°to reagents \! . ' ,.' - - ,. , A Azomethine ylides, as 1,3-dipolar reagents

Index

509

Benzene, reaction with :CH2 312, 324ff., Bis(trichloromethyl) carbonate 388 328, 372 Bis(trifluoromethyl)diazomethane 12, 37, Benzenediazonium ion, theoretical 145, 149, 255 investigations 167, 169ff., 457 Bis(trifluoromethyl)methanediazonium ion Benzodiazepines 239, 240 12, 255 Benzoquinone oxide 410 c/oso-Borane dianions 103 Benzoquinones, diazoBoranes - 1,2: azo coupling 395 f. - boron hydride-substituted diazomethanes reaction with O2 410 f. 324 - 1,4: as dipolarophiles 395 f. - cluster compounds of, 101 ff. - see also Quinone diazides Boron hydrides, see Boranes Benzothiazolazidinium salts, as diazo transfer Bridgehead-substituted alicyclic compounds reagents 49, 57, 59ff., 136f. 191 f. (Benzoyl)(phenyl)diazomethane, see 2-DiazoBuckminsterfullerene, see Fullerene[60] 1,2-diphenylethan-l-one Butane-1-diazonium ion, reaction with azide Benzylamine, deamination 293 ion 194 3-Benzyl-3-chlorodiazirine 178 Butenes, reaction with CH2N2 319 Bicycloalkenes and corresponding Butenylamines, deamination 288 heteroalkenes, as dipolarophiles 196, 220, [l-2H]-Butylamine, deamination 257ff., 262, 221, 222f.,238 290,291 - see also Bicycloheptenes, Norbornene [2-2H]-Butylamine, see 2-Methyl-[l-2H]Bicyclo[1.1.0]butanes, formation by propylamine 1,3-dipolar cycloaddition 231 4-(tert-Butyl)cyclohexylamines, epimeric, Bicyclobutanonium ion 289 deaminations 267, 278ff., 293 Bicyclo[2.2.1]heptan-l-amine, deamina(£)-l-Butyldiazenolate ion, dediazoniation tion 192 mechanism 249 Bicyclo[2.2.1]heptane-l-diazonium ion, (£)-2-Butyldiazenolate ion, see (£)-l-Methylreaction with azide anion 194 propyldiazenolate ion Bicyclo[2.2.1]heptene and derivatives, as tert-Butyldiazoacetate 52, 226 dipolarophiles 196 3-Butyl-3-phenyldiazirme 178 Bicyclo[2.1.0]pentanes, formation by y-Butyrolactones synthesis with diazoacetate 1,3-dipolar cycloaddition 231 carbenoids 365 f. 2,3-Bis(dialkylamino)cyclopropeniumdiazonium salts 92 ff. Bis(diazoalkanes), reaction with fullerene[60] QO, see Fullerene[60] 329 Carbamates, see 7V-Alkyl-7V-nitroso Bis(diazo)boranes 101 ff., 105 f. carbamates l,4-Bis(diazo)butane-2,3-dione, X-ray data Carbapenem, see Thienamycin 152, 154 Carbene anion radicals 406, 414 Bis(diazo)cycloalkanes 25, 46, 60 Carbene cation radicals 402f., 405, 406 3,6-Bis(diazo)cyclohexane-l,2,4,5-tetraone Carbenes 154 f. - bicyclic carbenes 337 f. ll,12-Bis(diazo)-ll,12-dihydroindeno[2,l-a]fluo- in combustion chemistry 321 rene, X-ray analysis and reactions 149 - cycloadditions with alkenes 311, 318ff., l,2-Bis(diazo)-l,2-diphenylethane 34 f. 321 f. 2,5-Bis(diazo)-l,6-diphenylhexane- dediazoniation of sulfonyl hydrazone 1,3,4,6-tetrone 33 anions 252 l,3-Bis(diazo)indan-2-one - from diazirines 315 - oxygenation 411 f. - diazoalkanes as precursors 4,43, 176ff., - Wolff rearrangement 346f. 306, 311, 314ff. Bis(diazo)indenofluorenes 405 - electrophilic, nucleophilic, and amphiphilic Bis(diazoketones) 357 carbenes 323f., 325, 338 l,10-Bis(diazo)octahydrodecaborate 3, 104ff. - general introduction 305ff., 313 /?,<5-Bis(diazo)-a,y,e-trioxo compounds 54f. - insertion reactions 312, 335ff., 345f. Bis(perfluoromethyl)diazomethane 149 - intramolecular reactions 313, 342f., 344, Bisperoxides 408 f. 345, 346 ff.

510

Index

- migratory ability of substituents 340 f. - monocyclic carbenes 337f., 341 - in photolyses of diazirine/diazoalkane systems 176 ff. - reactions with arenes 311, 324 ff. - reaction with fullerene[60] 330f. - reactions in matrices vs. solvents 344 - reactions with N2 308, 315 - reactions with O2 341 ff., 408 f. - reactivity index for carbenes :CXY (Moss) 322 ff. - rearrangements 312, 339 ff. (see also Wolff rearrangement) - rearrangements of cycloalkylidenes 341 f. - singlet-triplet interconversions, kinetics, and energies 307, 317, 318ff., 326, 335f., 337, 339, 342f. - stable carbenes 209 f. - substituted methylenes 308f., 320 - theoretical investigations 307, 309, 313, 316f., 323 - see also Methylene Carbene triplet sensitizers 317f., 335, 343, 409 Carbenoids - cobalt catalysts 359, 373f., 376 - copper catalysts 358f., 360ff., 367, 368, 372, 373 ff. - in cyclopropanations 358ff., 373ff. - definitions 306, 312, 314, 316, 318 - in dihydrofuran syntheses 361ff. - enantioselective reactions 373ff., 381 - formation (catalytic cycle) 358 - formation of 1,3-dipoles 369 f. - insertion reactions 364f., 367f. - mechanism of dihydrofuran synthesis 363 f. - palladium catalysts 359, 360f. - reviews 373 - rhodium catalysts 359, 360ff., 364ff., 372, 373, 376ff., 379ff. - ylide generation 368 f. Carbitol, see 2-(2-Ethoxyethoxy)ethanol Carbocations - alkenyl cations 417 f. - in dediazoniations of diazonium and diazenolate ions 241 f f., 249, 262 f f., 266ff., 271, 273f., 278ff., 308, 338 - in dehydrogenations of hydrazones 43, 44 - "hot" 273 - insertions 301 f. - nonclassical 280ff., 289, 290, 291 - strain in cyclic Carbocations 303 - structural information from NMR an IR spectra 282, 283 - in superacids 282ff., 288, 289

- theoretical investigations 282, 284, 287, 289 - X-ray analysis of a norbornyl salt 282 - see also Methyl cation Carbodiimide, comparison with CH2N2 184ff. Carbonium ions, see Carbocations Carbon monoxide, as carbene 305, 309 Carbonyl-de-diazoniation 106 Carbonyl oxides - as 1,3-dipolar reagents 199, 409 - intermediate in oxo-de-diazoniations 409 ff. Carbonyl ylides, as 1,3-dipolar reagents 198, 209 Carboranes 101, 102, 324 Carboxamides, 7V-alkyl-7V-nitroso 28ff., 133, 134 Carboxylic acid enol 354 Carcinogenicity - chemoprotection 130 - of Af-nitrosoamides and related compounds 129f., 131 - ofTV-nitrosoamines 127ff., 256 - of triazenes 131 f. Cascade reactions, see Tandem syntheses Chelate effect 442 Chloro-de-diazoniation 7, 93, 296 Chloroform, see Trichloromethane 2-Chloro-3-methylbutenediazonium salt 88 Clostridiwn pasteuricum 114 CN bond stability, in diazonium ions 168ff. 18-Crown-6 47 Crown thioether, in nitrogenase model reaction 111, 116 Crysanthemic acid ester, synthesis 230, 361 Curtin-Hammett principle, application to deamination 294 Cyanamide, comparison with CH2N2 142, 174ff., 184ff. a-Cyanodiazo compounds 59, 68f. Cyanodiazonium ion 100 Cyanogen, as dipolarophile 234 Cyanogen bromide, as dipolarophile 234 a-Cyanostilbene-4-diazonium salts 90 (Cyano)(trinitro)methane, as dipolarophile 234 Cycloadditions - of alkenylketenes 349 - carbene-alkene cycloaddition 323 f. - diazoalkanes with transition metal complexes 200 - see also 1,3-, 1,5-, 1,7-, and [3 + «]-Dipolar cycloadditions, and Diels-Alder reactions Cycloalkenes, as dipolarophiles 220 ff. Cycloalkyldiazomethanes 44

Index

511

Cycloalkylidenes 341 f. Cyclobutadiene - as dipolarophile 233 - formation 346 f. Cyclobutylamine, deamination 288, 300 Cyclobutyl cation 289 (-)-Cyclocopacamphene 236 f. Cyclodiiminomethylene, comparison with CH2N2 184 ff. Cycloheptatriene, formation 324 f., 326, 372 4-Cycloheptenyl cation 303 Cyclohexa-l,4-dienecarboxylate, as dipolarophile 232 f. Cyclohexylmethylamine, ring expansion by deamination 298 Cyclooctatetraene, as dipolarophile 233 Cyclopentadiene, as dipolarophile 205 Cyclopropanation, see Cyclopropane(s) Cyclopropanediazonium ion - dediazoniation 273 f. - reaction with azide ion 194 Cyclopropane(s) - "direct" formation from diazoalkanes and alkenes 229 f., 318 ff. - formation by azo-extrusion of a 4,5-dihydro-3#-pyrazole 229f - formation with carbenoids 358 ff., 373 ff. - formation catalyzed by one-electron donors

- of chiral methylamine derivatives 256 ff., 260 ff., 290 - compressed energy scale 302 f. - conformational control 260 ff., 271 ff., 278 ff. - elimination mechanisms 271 ff. - hydride shifts 272 f., 274 f. - initiated by (homolytic) electron transfer 255, 270 f., 293 - internal return (of N2) 294 - ion-pair intermediates 260 ff., 271 ff., 278 ff. _ mechanisms 5, 171, 191, 241 ff., 251 f., 253 ff., 256 ff., 260 ff., 267 ff., 290, 294 _ mechanistic nomenclature 241, 258, 260 _ micellar effects 268 f., 274 f., 295 _ molecular mechanics 287 _ rate-limiting formation of alkanediazonium ions 254, 255 - reviews of mechanisms 253 f. - solvent effects 266 ff., 284 _ stereochemistry 254, 256, 257 ff., 260 ff., 267 ff. _ sumrnary anci outlook (by W. Kirmse) 302 ff Decahydrodecaborate dianion 103 ff. Decahydrodecaborate diazonio anion 3,

? , *„, „„„ Cycopropene(s) 376, 378 Cyclopropemumdiazonmm salts - dediazoniation 93 f. - protonation 94 syntheses y^ i. - theoretical investigations 169 Cydopropenone ketals, as l,3-dlpolar reagents

Dediazoniation _ alkanediazonium ions llff . ? 16> 20ff., 241 ff 294 _ alkene'diazonium ions 194> 414ff. _ ^nediazonmm ions 112, 241, 259, 294 - azo-extrusion after 1,3-dipolar cycloadditions 218 f., 220, 229f., 234, 329 _ {n diazoalkane/diazirine rearrangements

Cyclopropen-3-yldiazoacetates 390f. Cyclopropenylketene 346 f. Cyclopropylamine, deamination 267 Cyclopropyldiazomethane, dediazoniation 288 2-Cyclopropylethylamine, ring expansion by H^arrvUiatirm oQs CycCopSthylaline, deamination 288, 289, 298, 300 (CyclopropylmethyDdiazenolate, dediazoniaton 288 Cyclopropylphenyldiazomethane 312 Cysteine, nitrosation 123

- of "diazo Compounds into carbenes 230 , „ v -~ f (see also sect. '•*) - homol of diazoic ketones 401 ff. ~ y^ » of diazoalkanes 241, 270 f. " mechanism, of alkyldiazenolates 248 ff. ~ °* m^^ complexes with diazenido hgands «9, 434, 437, 438, 439, 443, 446, 447, 452 , , , . , ' see alfso ™™c of compound or reaction for specific dediazomations Demjanov-Tiffeneau reaction 298 ff. , 304 2'-Deoxy-5-diazo-6-hydro-O^,5'-CyCloundine, X-ray analysis 154 Desoxynucleic acids, alkylation by diazoalkanes 19 7,7-Diacetoxy-iodobenzene (phenyliodosoacetate) 40 1,1-Dialkyldiazomethanes 48, see also 2-Diazopropane

Deamination - of alicyclic amines 278 ff. - applications in syntheses 295 ff. - of chiral 1-alkylamines 254, 256 f., 265 f.

512

Index

1,10-Diaminooctachlorodecaborate, diazotization 105 1,10-Diaminooctahydrodecaborate, diazotization 105 Diazald®, see 7V-Methyl-Ar-nitroso-4-toluenesulfonamide Diazald® II, see 7V-[(Ar-Alkyl-7V-nitrosoamino)methyl]benzamide Diazene(s) 116, 118, 431 Diazene intermediates, in deamination 279 Diazenide anions 41, 241 Diazenium ions, see Alkenediazenium ions Diazenols and -olates, see Alkyldiazenols and -olates Diazenyl radical 401, 402 f. 1,2-Diazepines 239 Diazetidine-l,2-diones 368 Diaziridine 175 l//-Diazirine - comparison with CH2N2 184ff. - substituted 188 f. 3//-Diazirine(s) - comparison with CH2N2 142, 174ff., 184ff. * - photolysis 176f., 181 f. - as precursor of carbenes and ketenes 314, 330, 350 - structure 175 f. - valence isomerization into CH2N2 176 Diazoacenaphthenone 256 Diazoacetaldehyde, see 2-Diazoethan-l-one Diazoacetamides 24f., 63, 364 - acylations 388 - alkylation 390 - in carbenoid reactions 361, 364, 373, 375, 377 - chiral esters 373 ff. - cycloaddition with alkenes 311,325,361 - "dimerization" 389, 396ff. - as 1,3-dipolar reagents 195, 196, 207, 213, 219, 224, 228, 234 - electrophilic substitutions of, 383 - formation of a-(aryliodonio)diazo compounds 392, 394f. - insertion reactions 312 - mass spectrometry 161 - metallations 286f., 452 - oxidation 411 - as precursors of diazonium ions in azo coupling reactions 192 - protonation 15, 139, 251, 255 - reactions with carbonyl compounds 388, 389 - reaction as C-electrophile 392, 394f., 396 ff.

- reactions mediated by diorganyl tellurides 372 - reaction with fullerene[60] 329 ff. - reaction with Meerwein reagent (Et3OSbCl6) 87 - reaction with 4-nitroaniline 62 - redox potential 406 - reduction 401 f. - in ring expansions 300 - rotamers 158 - structure 175 - synthesis 1, 3, 20, 52, 132, 138, 139 - X-ray analysis 148 Diazoacetoacetamides, for carbenoid cyclizations 366f. Diazoacetoacetate, ethyl 54, 371 Diazoacetone 13f., 255 Diazoacetonitrile 162 Diazoacetophenone, see 2-Diazo-l-phenylethan-1-one Diazoacetyl azide 24 f. O-Diazoacetyl-L-serine, see Azaserine Diazo aldehydes, see Diazocarbonyl compounds and 2-Diazoethan-l-one Diazoalkane cation radical 403 Diazoalkanes - acid-base equilibria 138ff., 251 - boiling points 19 - carbene formation 4, 312, 313, 315ff. - containing a heteroatom group 20 (see also 1-Diazo-N-, -P-, -S-, and -Sialkanes) - dediazoniations 4, 125, 128, 132ff., 138ff., 308, 315ff. - as 1,3-dipolar reagents 4, 196ff., 204, 221, 228, 234 (see also Diazomethane) - electron transfer to and from diazoalkanes 400ff. - N(yff)-electrophilicity 395 ff. - halogenation 383 - HMO investigations 162 - literature, general 9f. - mass spectrometry 161 - mechanisms of syntheses 132ff., 248ff. - metal-complex formation 317 ff. - metallation 384ff., 441 f. - molecular mechanics 165 - nitration 383 - oxidations 408ff., 414 - photolysis 18, 138f., 335ff. - reaction with Ar3C+ 392 - reaction with arenediazonium ions 138, 393 - reactions with Lewis acids 138f., 383ff. - redox potentials 406 - reductions 414

Index - structure and spectroscopy 148 ff. (see also Diazomethane) - synthesis by cleavage of TV-nitroso amides 17, 28 ff. - synthesis by dehydrogenation of hydrazones with metal oxides 17, 34ff., 40ff., 46ff. - synthesis by dehydrogenation of hydrazones without metal oxides 40 - synthesis by diazo transfer 17, 48ff., 63ff., 75ff. - synthesis by nitrosation 17, 20ff. - synthesis by ring opening of dihydrotriazoles 64 ff. - syntheses by other methods, see BamfordStevens reaction, Forster reaction - theoretical investigations, ab initio 161 ff., 166ff., 176ff., 184ff. - thermal stability 18 - toxicity 19 - use in industrial processes 361, 456 l-Diazo-7V-alkanes 20, 49 1-Diazo-P-alkanes 20, 26, 49, 50, 57f., 60, 73ff., 78, 81, 384, 386, 387, 389 1-Diazo-l-S-alkanes 20, 26f., 49, 50, 56f., 60, 387 l-Diazo-l-S/-alkanes 386f. - see also (Trimethylsilyl)diazomethane Diazoalkenes 39, 42f., 44f., 53, 78, 79, 159ff., 161, 370f., 379 1-Diazo-l-, -3-, and -4-alkoxyalkanes 31 a-Diazoamides, for carbenoid cyclizations 366 f. Diazoamidines 76 ff. Diazo anion radicals 401, 402 f. Diazoates, see Diazenolates Diazobarbituric acid 59 Diazobicycloalkanes and -alkanones 53, 154, 157 3-Diazobicyclo[2.2.1]heptanone 157 Diazobis(ethylsulfonyl)methane 56 Diazoboranes 101 ff., 104ff., 427, 433 f. Diazobutane 259 3-Diazobutan-2-one 157, 196 a-Diazobutylaldehyde 71 f. 3-Diazocamphor, X-ray analysis 154 Diazocarbonyl compounds - diazonio character of the diazo group 154, 159, 351 - formation of carbenes 344 ff. - oxidations 13ff., 85f., 140f., 251 - protonation 13ff., 85f., 140f., 251 - solvent effects 156 - structure and isomerisms 154ff., 158f., 163, 165, 351

513

- see also Diazoacetates, Diazo aldehydes, Diazo ketones, Ketocarbenes, Ketocarbenoids, Wolff rearrangement Diazocarbonyl oxides 409 f. Diazo cation radicals 402 f. Diazo chemistry, general history 1 Diazochloro- and -bromomethane 384 2-Diazo-5a-cholestanone 13 f. Diazo-Af-cyanoimines 78 Diazocycloalkanes 38, 39, 44, 53ff., 63, 79f., 154, 157, 302 Diazocycloalkenes 39, 44f., 163 Diazocycloheptatriene 163, 164 2-Diazocyclohexane-l,3-dione - 5,5-dimethyl 54 - synthesis 25 2-Diazocyclohexanone 53,157 Diazocyclopentadiene and derivatives 48, 135, 136, 150, 151, 162, 163, 164f., 202f., 425, 427, 441, 442 Diazocyclopolyenes (n = 1, 2, 3) 163 f. Diazocyclopropane(s) 302 Diazocyclopropene 163, 164ff. 2-Diazo-l-cyclopropenylethan-l-one 346f. £-Diazo-a,y-dicarbonyl compounds - BF3 complexes 26, 86 - in dihydrofuran synthesis 362f. - as 1,3-dipolar reagents 196 - protonation 86, 140ff. - structure and isomerism 154ff. - synthesis 25f., 33, 54ff. - in Wolff rearrangements 352ff. Diazodicyanomethane, see Dicyanodiazomethane Diazo-2,2-difluoroethane 22 Diazo-2,2-difluoroethene 82, 159f., 166 Diazodifluoromethane 162, 166, 183f., 188 2-Diazo-2,3-dihydrobenzothiophen-3-oxo1,1-dioxide 57 Diazodimedone, see 2-Diazo-5,5-dimethylcyclohexane-l,3-dione 2-Diazo-5,5-dimethylcyclohexane-l,3-dione 25, 373 Diazodinitromethane 384 3-Diazo-l,4-diphenylbutan-2-one 157 2-Diazo-l,2-diphenylethan-l-one - dediazoniation 352, 357 - electron-transfer kinetics 402 f. - electron-transfer products 414 - NMR data 151 - synthesis 34, 46, 51, 136 Diazodiphenylmethane, see Diphenyldiazomethane 2-Diazo-l,2-dipyridylethan-l-one, ring closure to triazole 35

514

Index

Diazoenols (tautomers of diazocarbonyl compounds) 156, 158f., 160 Diazo esters, see Diazenolates Diazoethane - boiling point 19 - as 1,3-dipolar reagent 321 - metal complex formation 440 - as precursor of ethanediazonium ion in azo coupling reaction 192 - protonation 13 f. - synthesis 32 f. - theoretical investigations 162 - UV/VIS spectrum 150 2-Diazoethan-l-one - dediazoniation 317, 351 f., 357 - structure and isomerism 158, 163 - synthesis 30, 71 f. Diazoethene and derivatives 81 f., 159ff., 166, 371 Diazoethylidene derivative 80 9-Diazofluorene and derivatives - electron transfer 402, 404f. - dediazoniation 256, 320 f. - metal complexes 445 - NMR data 151 - reaction with O2 410 - redox potential 406 - synthesis 44, 46 - X-ray analysis 148 Diazofluoromethane 162,164 2-Diazo-l,l,l,3,3,3-hexafluoropropane, see Bis(trifluoromethyl)diazomethane Diazohydrazides, for intramolecular carbenoid reactions 368 Diazohydroxides, see Diazenols 16-Diazo-3/?-hydroxyandrost-5-en-17-one 46 a-Diazoimidates 76 f. Diazoindandiones - 1,2,3: oxygenation 411 f. - 2,1,3: oxygenation 411, 413 2-Diazoindan-l-one(s), synthesis 46 3-Diazoindazole, X-ray analysis 148 3-Diazo-3#-indole 66 3-Diazoindolin-2-one, rearrangement into corresponding diazirine 180f. Diazo ketone/diazirine rearrangement 180f. Diazo ketones - acylation 387 - carbenoid reactions 361, 363ff., 369f. - cyclic 53, 157, 410 - diazo ketone/diazonio enolate mesomerism 14f., 25, 89f. - as 1,3-dipolar reagents 196, 198 f. - mass spectrometry 160 - mechanism of formation by diazo transfer 135 f.

-

polarography 401 f. protonation 13ff., 139, 140, 251 reaction with carbonyl compounds 388 reaction with NaBH4 414 rotamers 157 f. structure 14f., 25, 89f., 152ff., 157ff. syntheses 16, 20, 25, 30, 34ff., 37f., 46f., 51 ff., 388 - Wolff rearrangements 3, 345ff., 351 f. Diazomalonates 86, 372, 402, 406, 441, 452 Diazomalonitrile 37 Diazomalonodialdehyde 25 Diazomalonyl chloride, ethyl 388 Diazomethane - acid-base equilibria 140f., 247, 256 - acylation 387 - in Arndt-Eistert reaction 345, 357, 387 - boiling point 19 - bond angles and lengths 146f., 149, 162 - charge distribution 162 - in Chemical Abstracts 1 - deprotonation energy (calc.) 87, 316 - as 1,3-dipolar reagent 195, 196, 201, 203, 207ff., 212ff., 216, 217, 218, 220, 226ff., 228f., 234, 237f., 329 - enthalpies of formation (calc.) 185 - formation of epoxide 389f. - formation from isopropyloxyethene 67 - formation of methylene 316 ff. - formation of polymethylene 5, 173 - history 2, 29, 455 - HMO investigations 162ff., 316 - in homologizations of aldehydes and ketones 299f., 357f. - hypervalent structures 166 - insertion reactions 335 ff. - instability (explosions) 18 - IR spectra 147, 149 - isoelectronic compounds 97, 147, 173 - isomeric compounds 142, 173ff., 182ff. - isomerization to/from diazirine 163, 176f., 182ff., 316, 317 - isotopically labeled 32, 147 - retaliations 386f., 440, 446, 451, 452 - as methylation reagent 295f., 304 - MO investigations 97, 160ff., 166ff., 168ff., 176ff., 184ff. - NMR data 145, 147, 151 - nucleophilicity 12, 300, 383 - photolysis 176f., 182, 308, 312, 316 - potential energy surface 187 - as precursor of methanediazonium ion in azo coupling reactions 192 f. - protonation llf., 166, 170, 191 f. - reaction with alkenes 319 f.

Index - reaction with arenediazonium ions 138, 234 - reaction with CO 306 - reaction with fullerene[60] 329 - reaction with lithiodiazomethane 396 - reaction with metal atoms 454 - reduction 402 - for ring expansions 298, 299f., 372 - substituent effect (theory) 162f. - syntheses 2, 29ff., 46, 47, 48, 98 - tetrahedral boron-hydride substituted 324 - theoretical investigations (ab initio) 162 ff., 166 ff., 316, 351 f. - toxicity 19 - UV/VIS spectrum 31, 147 - VB investigations 165f. Diazomethanedisulfonic acid 26 f. 5-Diazo-6-methoxy-5,6-dihydrouracil, X-ray analysis 154f. Diazomethyl anion 142, 174 (Diazomethyl)diphenylphosphine oxide 26 Diazomethylene 97 Diazomethylphosphonates 81, 159 Diazonaphthoquinones, see Quinone diazides Diazonio group - bonded to sp2-C atom 83, 414f. - bonded to sp-C atom 91 ff. - at bridgehead carbon 15, 191 f. - charge distribution 168ff., 172, 457 - notation 168ff., 457 9-(Diazoniomethylene)fluorene 88 3-Diazoniopropenoic acid, structures of rotamers 171 f. 9-Diazoniotryptycene-l,4-dione cation, trapping with 2-naphthol 191 2-Diazonitriles 49, 57 Diazonitrite 269 f. Diazonitromethane 384 Diazonium ions, inorganic 95ff., 101, 112, 457 Diazonorcamphor 157 Diazooctane - dediazoniation 252 - synthesis 22 4-Diazooctane, dediazoniation 252, 271 f. Diazo-l,2-oxaphosphetanes 81 cr-Diazo-/?-oxoaldehydes 56 2-Diazo-3-oxobutyrates 362 . 3-Diazo-2-oxopropionate, in dihydrofuran synthesis 361 ff. 6-Diazopenicillic ester 24 f., 408 5-Diazopenta-l,3-diene, as 1,5 dipolarophile 239 3-Diazopenta-2,4-dione 362 3-Diazoperfluorobutanone 177 2-Diazo-3-(phenylamino)propionates 67f.

515

l-Diazo-4-phenylbutan-2-one, cyclization and ring expansion 365 2-Diazo-l-phenylethan-l-one - alk-2-enyl- and alk-2-ynyl-substituted 346 ff. - IR data 157 - polarography 401 - structure 154, 158 - Wolff rearrangement 345ff., 357f. l-Diazo-3-phenylpropan-2-one 388 3-Diazo-3-phenylpropan-2-one 51 a-Diazophosphinates 44f., see also DiazoP-alkanes a-Diazophosphonates 44f., see also DiazoP-alkanes a-Diazophosphonium salts 74 f. 2-Diazopropane - as 1,3-dipolar reagent 73, 78, 201, 213, 218, 219, 222f., 230, 232 - as ligand 450 f. - theoretical investigations 162 l-Diazopropan-2-one 156, 157, 158 3-Diazoprop-l-ene 79f., 236, 238f. Diazopropyne 162 Diazoquinones, see Quinone diazides Diazosilane 101, 183, 188f. a-Diazo-/?-silylketones 82 Diazo sulfones 251 7-Diazo-6,6,8,8-tetrafluorotridecane, photochemical isomerization into corresponding diazirine 177 Diazotic acids, see Diazenols Diazotization - of aliphatic amines 16f., 20ff., 244 - of 2-aminoazulene derivatives 20 f. - of /?-amino-a,y-dicarbonyl compounds 25 ff. - in aprotic solvents 245 f. - of aromatic amines 15, 96, 98, 121, 122 - in glacial acetic acid 244 - of inorganic amines 95 ff. - "intra-complex" 433 f. - kinetics (aliphatic amines) 121 ff. - mechanisms (aliphatic amines) 121 ff., 132 ff. - with metal nitrosyl complexes 21, 27, 124ff., 132, 245, 433 - micellar catalysis, intermolecular 269 - micellar catalysis, intramolecular 122, 244, 268 f., 274 f., 295 - phase-transfer catalysis 21 Diazo transfer reactions - deformylating transfer 52 f. - diazo transfer reagents 48, 49, 50, 51, 52, 54, 57, 59f., 61 f., 67, 136f.

516

Index

- in 1,3-dipolar cycloadditions 63 ff., 70 ff., 75 ff. - to enamines 63 ff. - to enol ethers 67 - to indole 66 - mechanisms 134 ff. - phase-transfer catalysis 50, 56 - by polymer-bound arylsulfonyl azides 56 - in syntheses of aromatic diazo compounds 49 - in syntheses of diazoalkanes 17, 48ff., 63ff., 75ff. - in syntheses of triazoles and dihydrotriazoles 63ff. - to transition metals 108f., 113 - via triazenes 62 f. l-Diazo-2,2,2-trifluoroethane 22f., 41 l-Diazo-2,2,2-trifluoro-l-phenylethane 179 3-Diazo-l,7,7-trimethylbicyclo[2.2.1]heptan-2one, see 3-Diazocamphor Diazynium ion (N2H+), formation 2, 95, 96 Dibenzoyldiazomethane 441 f. Di(tert-butyl)diazomalonate 56 Di(tert-butyl)diazomethane 19, 43, 219 Dichlorocarbene 306, 330 2,2-Dichloroethenediazonium salts 88, 146, 172 Dictyopterene B 236 Dicyanodiazomethane 149, 193 Dicyanomethylene 311 Diels-Alder reactions 202, 203, 217 2,2-Diethoxyethenediazonium salts 88, 146, 160, 172, 415f. Diethynyl carbenes 331 Difluorodiazirine 188 Difluorodiazoethene, see Diazodifluoroethene Difluorodiazomethane, see Diazodifluoromethane Dihydrofurans, syntheses with diazocarbonyl compounds 361 f., 364 l,2-Dihydronaphthalene-3-carboxylate - chromium(tricarbonyl) complex as dipolarophile 227 f. - as dipolarophile 226f. 4,5-Dihydro-3/f-pyrazoles 212ff., 224ff., 229, 231, 236, 237, 329, 330, 331 4,5-Dihydro-A2-l,2,3-triazole and derivatives - nomenclature 64 - reactions 68ff. -synthesis 63 ff. 2,2-Dihydroxyindan-l,3-dione 411,413 Dimethoxycarbene 330f., 338 4,4-Dimethyladamantyl-2-amine, deamination 267 (2/?,35)-l,2-Dimethylbutylamine, deamination 267

A^A/^'-Dimethyl-A^TV'-dinitrosoterephthalamide 30 f. l,2-Dimethyl-2-norbornyl cation 284f. 1,2-Dimethylpropylamine, deamination 243 Dinitrogen - addition to methyl cation 143 - addition to phenyl cation 95 - bond length 96 - dissociation energy 116 - internal return of N2 in deaminations 294 - isoelectronic with CO 107 - as leaving group in alkanediazonium ions 303 - as ligand of metal complexes 3, 107ff., 114ff., 117f. - protonation 2, 95, 96 - reaction with carbenes 308, 315 Dinitrogen fixation, see Nitrogen fixation Dinitrogen oxide - as 1,3-dipolar reagent 198, 207, 208 - formation 95 - isoelectronic with CH2N2 97 f. - as leaving group 252, 253, 260ff. - methylation 100 - reaction with alkyl anions 257 1,2-Dioxetanes 392, 394 Dioxides of carbon 60 Dioxiranes, as oxidation reagents 411, 413 1,3-Dioxolanes 392 1,3-Dioxolium salts 89, 419 Diphenylcarbene and derivatives 309, 320, 337, 338, 344, 357 Diphenyldiazomethane 36f., 39, 46, 139, 140, 150, 222, 234, 256, 263, 312f., 329, 334, 392f., 402ff., 406, 408, 410, 439, 445, 450 2,2-Diphenylethenediazonium ion 83 Diphenylmethanofullerene[60] 234 Diphenyl phosphatidate (DPPA), as diazo transfer reagent 50 Disphosphonium ions (R-P 2 + ) 172f. Diphosphorus, protonated 96 1,3-Dipolar cycloaddition - competition with azo coupling 193f., 234 - concerted vs. stepwise cycloaddition 208ff., 211 f., 222f. - diastereoselectivity 224ff. - 1,3-dipolar reagents, list 198 f. (see also 363, 370) - electron notation 210ff. - frontier orbital approach 202, 215f., 217 - Hammett relationships 206,207 - history 3f., 139, 195f., 455 - intramolecular 214, 235, 237, 238 - leading to dimerization 348 - mechanism 200 ff.

Index - molecular mechanics 212, 226 - in natural product syntheses 235 ff. - in reactions of diazoalkanes with fullerene[60] 329, 330 - regioselectivity 212 ff., 217 ff., 222 f. - reviews 200, 228 - 1,7-ring closure 211 - solvent effects 210 - stereospecificity 199, 208 ff. - structure-reactivity relationships 204 ff., 207 ff. - theoretical investigations 202 ff., 216 ff., 226 - 1,2,3-triazole formation 63 ff. - use of diazoalkane precursors 235 - VB investigations 166 1,5- and 1,7-Dipolar cycloadditions 211, 238 ff. [3 + «]Dipolar cycloadditions, n = 1 vs. n = 2 200 Dipolarophile, definition 4, 196 f., see also specific compounds 1,3-Dipolar reagents - allyl type 197 ff., 203 - biradical character 197 - definition 196 - examples 4, 195 ff. - list 198 f. - propargyl-allenyl type 197 ff., 203 Dipole moments, of rotamers of diazocycloalkanones 157, 164, see also specific compounds

517

Ethenediazonium ion 169, 171, 172, 415, see also Alkenediazonium ions Ethenediazenium ion 145 f. Ethenedicarboxylic acid and esters, as dipolarophiles 195, 199 Ethenes, substituted, as dipolarophiles 208 ff., 215, 216, 217, 229, 234 Ethenyl carbenes 331, 337 Ethoxyethene, as dipolarophile 216, 217 2-(2-Ethoxyethoxy)ethanol 31 Ethylamine - deamination 295 - [l-2H]labeled 295 l-Ethyl-2-azidopyridinium ion 61 3-Ethylbenzothiazol-2-azidinium tetrafluoroborate, see Benzothiazolazidinium salts (£>Ethyldiazenolate ion (and 2-substituted), dediazoniation mechanism 249 f. (Z)-Ethyldiazenolate ion, 2,2,2-trifluoro, dediazoniation mechanism 249 f. (2S)-l-Ethyl-2-methylbutylamine, deamination 274 f. Ethyne 228, 229 Ethynediazonium ion 169 Ethynedicarboxylates, as dipolarophiles 194, 203, 228 Ethynes, in 1,3-dipolar cycloadditions 213 f., 229 Eximer laser resist technology 346

co-npo-, m. 128, Dodecahydro-dodecaborate dianion 102, 103 Domino reactions, ^Tandem syntheses DPPA, see Diphenyl Phosphatidate Dual substuuent parameters (DSP) -torcaroenes i^i., w - for metal complexes with diazenido ligands Dutene, nitration 292

87r-Electrocyclization 239 Electronegativity, in metal-ligand bonding 430 Enamines, as dienophiles 63 ff., 67, 71 f. Ethanediazonium ion 145, 169, 170, 193 Ethene - as dipolarophile 203 f., 216, 228 - reaction with carbenes 321, 322

99f.( 169f.; 457 Pormonitrile imine, see Nitrile imine Formonitrile oxide, see Nitrile oxide Forster reaction 46f. Friedel- Crafts alkylation, with ./V-nitroso amides 301

F l u o o m u m ion

"taSof^iazoalkanes with C60 230, 234, 329 ff. - reaction of 2-diazoniobenzenecarboxylate (as benzene precursor) 334 Fulvenes, comparison with diazocycloalkenes 164 Fumarates, as dipolarophiles 194, 210, 211 Furan ~ 2,3-dihydrofuran as dipolarophile 67 - as dipolarophile 205 - reaction with :CH2 325

518

Index

Gas-phase reactions - :CH2 312, 315, 321 f., 325, 326 - methanediazonium ion 15 L-Glutamic acid, deamination 246 Glyconothio-O-lactone, as dipolarophile 219 f. Guanidines, 7V-alkyl-7V-nitroso 28f., 32 ™ i **r>rTT i Haber-Bosch process 118f. Ha ogeno-de-metallation 385 6S> re 6S 320 322 ' . Hammett equation - dediazoniation of ^diazo-l^-diphenylethan-l-one 352 - m 1,3-dipolar cycloadditions 206 207 - nucleophilicity of N(a) in diazenido metal . Afr. complexes 450 - see also Dual substituent parameters Hammond postulate applications to dominations 294 Hard and Soft Acid and Base principle 127, 430 Heteroaromatic systems, as dipolarophiles 67, 205, 228 Homocubaneamine, deamination 191 Homocubyl-AT-nitrosoacetamide 191 Hydrazoic acid 97f., 100 Hydrazones, dehydrogenation 34 ff. Hydride shifts 272f., 274f., 278ff., 288, 298 Hydrophobic interactions 268, see also Deamination, Diazotization Hydroxy-de-amination 1, 244, 296, 297 ff. Hydroxy-de-diazoniation 357, see also Hydroxy-de-amination Hydroxydiazonium ion 100, 169 Hydroxylamine, diazotization 95, 96 ff. 4-Hydroxyproline, nitrosation 123 Hyellazole 349

Imaging technology 90, 346 Imidazolium ions 392 Imidazol-2-ylidenes 310 Inertness, see Stability Ion-pair intermediates, see Deamination Iron molybdenum cofactor (FeMoco) 115f. 7V-Isocyanamide, see Aminoisonitrile Isocyanides 305, 309 Isodiazirine, see 1//-Diazirine "Isodiazomethane" 174 Ketene hydrate(s) 354f. Ketene(s) 5, 147, 163, 164, 228, 306, 315, 321, 345ff., 350ff., 354ff.

Ketenes, cyclic 164, 356 Ketocarbenes 345 ff., 350ff., 354ff., 363 Ketocarbenoids 199, 360, 361, 362ff., 370f., 373 ff. /?-Lactams, synthesis by intramolecular carbenoid reactions 366f. Lactones _ intermediates in deamination of ^^ adds 2% ^ - y: by dimerization of ketenes 345f- y: formation in intramolecular carbenoid reactions

365f

(S)-tert-Leucine, deamination 296f. Lithiodiazoacetates _ carbenoid reaction with thiolactones .• ^Qjoo ^ ~~f lormauon Lithiodiazoalkanes 173,386,396 (+)-Longifolene 235, 236 Loracarbef, see Thienamycin L-Lysine, bisdeamination 248

369

M

*gic acid, see Super acids Maleates, as dipolarophiles 194 Mercury derivatives of diazoalkanes

384ff.,

391

Mercury oxide, as dehydrogenation reagent 34ff. complexes, see Transition metal complexes Metallo-de-hydrogenation 385 ff. Metallo-de-metallation 386 Metal nitrosyl complexes ~ in diazoalkane syntheses 21, 27f., 132 ~ see also Pentacyanonitrosyl ferrate Methaneazophosphonium ion (H 3 C-PN + ) 173 Methanediazonium ion 12f., 15, 100, 141 ff., 145f., 167ff., 171, 247, 457 Methanephosphazonium ion (H 3 C-NP + ) 173 Methanephosphonium ion (H 3 C-P 2 + ) 173 Methanesulfonyl azide 50, 67 l,6-Methano[10]annulenes - synthesis and structure 327, 329 - imino analog 328 Methanofullerenes[60] - syntheses 329 ff. - structure of isomers 330ff. Methenediazenium ion 145 f. 1- and 2-Methoxybuta-l,3-diene, in dihydrofuran syntheses 362f. Methoxydiazonium ion 100 (4-Methoxyphenyl)diazomethane 150

Metal

Index

519

(3-Methylalkan-4-yl)amines, deamination Neighboring group participation 258, 276, 274 f. 277, 295 f., 298, 303, 304 1- and 2-Methylallyl ion 273, 289 Ninhydrin hydrate, see 2,2-DihydroxyindanMethylamine 1,3-dione - chiral derivative 256 f. Nitrenes 314 - nitrosation 22, 291, 295 Nitrile imine(s) 2-Methyl-3-aminobutane, see 1,2-Dimethyl- comparison with CH2N2 47, 156, 174, propylamine 184 ff. Methyl cation - as 1,3-dipolar reagents 198, 204, 239 f. - stabilization by cyclopropyl groups 289 Nitrile oxides, as 1,3-dipolar reagents 195, - theoretical investigations 167, 170 f. 198, 204, 216, 217 Methyldiazenolate ion Nitrite's, as dipolarophiles 234 - (Z): 22, 256 Nitrile ylides, as 1,3-dipolar reagents 198, - (£): 247 f., 256, 265 209 Methylene 5, 97, 181, 305 f., 307 f., 312, 315, 7V-Nitroamides, as source for carbocations 317, 321 f., 324 f., 337 253 2'-Methyleneadenosine derivative, as 7V-Nitrocarbamates, as source for carbocations dipolarophile 237 f. 253 Methylenediazenium ion 12 f. Nitrodiazo compounds 59 1-Methylethylamine, deamination 295 Nitrodiazonium ion 100 1-Methylheptylamine, micellar catalysis of Nitrogenase enzymes nitrosation 244, 268 ff. _ biochemistry and structure 3, 107, 114 ff., 5-Methylhexa-2,4-dienolate, as dipolarophile ^g 2 ?° . . - model compounds for, 116f. Methylidyne radical, in photolysis of CH2N2 _ products in nitrogen fixation 117, 118 97 , t , . . . t. Nitrogen fixation N-Methyl-N-nitro-N-nitrosoguanidme, as _ chemical steps in, 111, 114, 115 ff. carcinogen 129 ff. _ energetics 118 f. 7V-Methyl-7V-nitrosocarbamates, see 7V-Alkyl_ njstory 3 jQ7 113ff N-nitrosocarbamates - see also Nitrogenase enzymes am C 32 ltrOS° t0 Nitrogen oxides (NO,, etc.), as nitrosation 290, 292 l-Methyl-2-,^o-norbornylamme, deamination

DMUoge oxide Nitromethylene 309 Nitrones> ^ Azomethine oxides

_x/rll * , ,. , • <,™ (2-Nitrophenyl)diazomethane, photolysis 344 7-Methy octa,6-diene, cyclopropanation 359 Nit side> 'sodium, see Pentacyanonitrosyl 2 2-Methyl[l. f . ._ „ H] -propylamine, deamination rerraie / oi™ u i i j • .Nitrosan, see AA,7V'-Dimethyl-A^A^'-dinitrosomme> deammatl n 267 29? ° ° terephthalamide (£)-l-Methylpropyldiazenolateion, Nitrosation dediazoniation mechanism 248 f., 292 - of a-ammo acids 123 N-(l-MethylPropyl)-N-nitroso-4-toluene' of 2-amino-l 3-dicarbonyl comsulfonamide 292 P°unds 25ff ' ... Micellar effects, see Deamination, Nitrosation P1 am™?01* A/51;. . . Microdiffusion, influence on product ratio ' m,tPTtlC f 1VCntS £5£ ~ °f hydroxylamme 95, 96, oof 98 f. ^c/o-Myrtanylamine, deamination 298f. ~ of isocyanatoethenes 88 - literature, general 10 - mechanisms (aliphatic amines) 121 ff. , 242 ff. Nakafuran-8 390 - with metal nitrosyl complexes 27 f., 113, Naphthalene, reaction with carbene precursors 124 ff., 132, 245 325, 326, 327 f., 372 - micellar catalysis 122, 244 Naphthoquinone diazides, see Quinone - with nitrite ions 126 f. diazides - phase-transfer catalysis 21

520

Index

- of primary aliphatic amines 5, 10, 20ff. - of secondary aliphatic amines 27 7V[(7V-Nitrosoalkylamino)methyl]amides 28 f., 133, 134 7V-Nitrosoamides - for alkylations of aromatic hydrocarbons 301 - 14C-labeled, 260f., 262f. - reactions in presence of Rh catalysts 372 -rearrangements 246, 252, 261 ff., 271 ff., 278ff., 293, 295, 303 - see also M^-Nitrosoalkylamino)methyl]amides TV-Nitrosoamines - acid-base equilibria 129 - from amines with metal nitroso complexes 126 - carcinogenicity 127ff. - formation in living organisms 130 - from primary aliphatic amines 121 ff. - from secondary aliphatic amines 122 ff. - solvolysis 129 f. W-Nitrosobutyramides, deamination 279 7V-Nitrosocycloalkylamines, carcinogenicity 127 f. Af-Nitrosodialkylamines, carcinogenicity 127 f. Nitrosohydroxylamine 98 7V-Nitrosomethylurea 19 3-Nitroso-l,3-oxazolidinones, solvolysis 84 f. Af-Nitroso-A/-(l-propylpentyl)butyramide, deamination 271 f. 7V-Nitroso sulfamates 246 Nitrosyl chloride 21 f., 245f. Nitrosyl ruthenium complexes 111 Nitrous acid, scavengers for, 123 f. Nitrous oxide, see Dinitrogen oxide NN bond lengths - arenediazomum ions 104 - azo compounds 146 - l,4-bis(diazo)butane-2,3-dione 152 - cyclic diazocarbonyl compounds 155 - diazenido complexes 440, 453 - diazoboranes 104 ff. - diazocycloalkanes and related compounds 148 f - 2-diazo-l,2-diphenylethan-l-one 154 - diazomethane 146f. - dinitrogen 96, 167 - metal complexes with N2 108, 109, lllff. - theoretical investigations 162, 164, 167 - see also under name of compound(s) N (a), N (/?) rearrangement - in aromatic diazonium ions 111 - in metal complexes of N2 111

Nomenclature - of diazo compounds 6f. - of reaction mechanisms 6, 7ff. - of reactions 6 - terms in physical organic chemistry 9 Norbornanediazonium ions - 2-: dediazoniation 290 - 6-: dediazoniation 252 Norbornene(s), as dipolarophiles 222 f. Norbornyl-2-amines, deamination - endo: 280, 284ff., 290, 291 - exo: 267, 280, 284 ff. ex °- an<^ endo-2-Noibomyl 4-bromobenzenesulfonate, nonclassical - carbocation in acetolysis 280f., 287 2-Norbornyl cation - 6-bridged 280ff., 285ff. ~ 7-bridged 285, 303 ~ classical 281 f., 284, 286f. ~ 1,2-dimethyl 283 ~ 6,6-dimethyl 286 " ion pairs 285 f. ~ other substituted 286 f. - 1,2,4,7-tetramethyl 282 " see also Carbocations 1-Norbornyldiazomethane, carbene formation 339 Norcaradiene 311, 325, 326

j_ and 4-Octanediazonium ion, see 1- and 4-Octylamine (£Z)-l,3,5-Octatriene, as dipolarophile 236 j. and 4_octylamine _ deamination of 4-octylamine 264, 271 f. -l[l-2H]-octylamine, deamination 259, 269 _ yields in various deamination processes 251 f 269 272 f Octyl-2-diazenolate, chiral, deamination 18 w j tn H2 O 264, 265 6/M,3,4-Oxadiazines 415 f. Oxadiazoles _ 1^,3: as valence tautomers of diazo ketones 152 _ i>2,4: carbene precursors 330f. _ 1,3,4: from alkenediazonium salts 415 f. Oxetanes 376 Oxindols, formed in photolysis of 3-diazoindolin-2-one 181 Oxirenes, in ketene reactions 345, 350f., 354 Oxo-de-diazoniation 408 f f., 411 ff. Ozone, as 1,3-dipolar reagent 195, 199, 207, 208

Index (-)CR)-Panolactone 379f. Pentacyanonitrosyl ferrate, disodium, as nitrosation reagent 27f., 124ff., 132, 245, 274f., 298 Pentamethylenediazirine 175f., 178, 180 Peptides, nitrosation 124 Peroxides, in oxygenation of diazocarbonyl compounds 409 ff. Phase transfer catalysis, in syntheses of diazo compounds 21, 40, 56 Phenonium ion intermediate 277, 392 1-Phenylcyclobutene 312f. Phenyldiazomethane - in cyclopropanation 359 - as 1,3-dipolar reagent 235 - metal complex formation 440 - precursor as 1,3-dipolar reagent 235 - reaction with fullerene[60] 329 - in ring expansion 389 - synthesis 22, 39, 150, 151 1-Phenylethylamine, chiral, deamination 260 ff * (£)- and (ZH-Phenylethyldiazenolate ion - (£): dediazoniation 248f., 265 - (Z): dediazoniation 265 2-Phenylethynediazonium salt 91, 92 Phenyl group shifts 276f., 303, 392 l-Phenyl-3-(l-propylpentyl)triazene, deamination 271 f. Phenyl(pyridm-4-yl)diazomethane, protonation 87

l-Phenyl-2,2,2-trifluorodiazoethane 12, 145 Phenylurea, as scavenger for HNO2 124 Pmacolic deaminations 280 Pmguisane 390 Polymethylene 5, 173 Proline, nitrosation 123 Propa-l,2-dienes, as dipolarophiles 211 Propadienone 81 Propanediazonium ion 170 Propene, as dipolarophile 216 3-Propenediazonium ion, dediazoniation

521

Radical scavengers, in homolytic deaminations 271 Rhizobium microorganisms 114f. Rhodium catalysts and complexes 359, 360ff., 364ff., 372, 373, 376ff., 379ff., 456 Ring contractions - in deaminations of alicyclic amines 278, 288, 298, 300 - dediazoniations of cyclic diazo ketones 346 f. Ring expansions - in carbenoid reactions 365, 371 f., 376 - of cyclic ketones with CH2N2 299f., 389 - in deamination of alicyclic amines 288, 298 ff. - of l,6-methano[10]annulene with CH2N2 299f., 389 Ruthenium nitrosyl complexes 28, 113

Sarcosine, nitrosation 123 Sensitizers, see Carbene triplet sensitizers Shapiro reaction 42 Silacarbodiimide 188 Siladiazirine 188 Siladiazoalkanes 82 silane

321f

Silverdiazoalkanes 384,386,390 silyldiazo ligand 453 Silylenes 314, 321 f. (Silylphosphonvl)diazomethanes 50 (Silylsulfonyl)diazomethanes 50 Skell-Woodworth rule 318f., 320 Stability, thermal vs. "kinetic", definition jg3 433 Sulfamic acid, as scavenger for HNO2 123 f. Sulfonamides, JV-alkyl-7V-nitrosoarene- 28 ff. Sulfonyl hydrazone anion, photolytic deamination 251 f., 303 Superacids 282, 288, 289, 291 Sydnones, as 1,3-dipolar reagents 199, 201 f.

2,1 j

(£)-3-Prop-2-enoate, methyl, as dipolarophile 224 Propylamine, deamination 242, 243 (l-Propylpentyl)amine, deamination 271 f. 3//-Pyrazoles 78, 213 f., 222f., 224, 226, 228f 238 f Pyrazolines, see 4,5-Dmydro-3//-pyrazoles Pyridazines, as dipolarophiles 225 Pyryliumions 391 1,2- and 1,4-Quinone diazides 25, 27, 154f., 161, 198, 354, 355, 356f., 410f., see also Benzoquinone, diazo-

Ta Qm

^ syntheses, of carbenoids 370ff., 380 I6!1™!68 3/r ... ,u 2,3,4,5-Tetrachloro-6-diazocyclohexa-2,4-dien1-one, as 1,3-dipolar reagent 199 Tetra(diazo)hexaoxo compound 54f. Tetrahydrofurans 376 l//,4/M,2,4,5-Tetrazine-3,6-dicarboxylates - formation from diazoacetate 396ff. - as synthons 397 ff. Tetrazoles - from azido-l,2,3-triazoles 77 - azo-extrusion in flash thermolysis 187

522

Index

1,2,3- and 1,3,4-Thiadiazoline 218 2-Thia-5-norbornanediazonium ion, dediazoniation 252 Thiazolium ions 392 l,3-Thiazol-5-(4//)-thiones, reaction with diazoalkanes 218 f. Thienamycin 51, 367 Thieno[3,2-£]thiophene derivatives, as azo coupling components 192f. Thiiranes, formation in 1,3-dipolar cycloadditions 219 f. Thiocarbonyl ylides, as 1,3-dipolar reagents 211 Thioformaldehyde, as dipolarophile 218 Thioketones, as dipolarophiles 218 Thionyl chloride, reaction with diazenolates 268 Thiopyrylium ions 391 Tiffeneau reaction 298 ff., 389 Toluene - formation from :CH2 + C6H6 312, 325 f. - reaction with :CH2 325 Transition metal complexes - with alkyldiazenido ligands, structure 439 - with alkyldiazenido ligands, syntheses 439ff. - with aryldiazenido ligands, structure 422, 424 ff. - with aryldiazenido ligands, syntheses 111, 43Off. - with diazenes 422, 430, 431, 432, 435 - with hydrazines and hydrazides 422, 427, 433, 435, 447f. - metalloazines 444 - metals involved in diazenido complexes 423

456

- with N2 3, 107ff., 438, 441 f., 446ff., A*,- nomenclature 422, 423, 427, 437 - with silyldiazenido ligands 453 - structural types and analyses 424ff., 4 ~ sf Triazenes - l-alkyl-3-aryltriazenes as source for n j. • • ^cn 252, ">£*> 271 ~>n
; ,. , . ,. , ,. f - as intermediates in diazo transfer reactions 62 f. - mutagenicity 131 f. 1,2,3-Triazoles 63f., 68, 75ff., 234, 415f. A2-l,2,3-Triazoline, see 4,5-Dihydro-A21,2,3-triazole (2,4,6-Tri(tert-butyl)phenyl)phenyldiazomethane 342 ff. Trichloromethane, hydrolysis 305, 306 2,2,2-Trifluorodiazoethane 133, 250

2,2,2-Trifluoroethanediazonium ion 2, 12, 145 f. (Trifluoromethyl)diazoalkanes 40 (Trimethylsilyl)diazomethane 18, 50f., 186, 296, 386, 389, 390, 440 Trimethylsilylketene 356 (Trimethylsilyl)phenyldiazene 431 Triphenylcarbocation, reaction with Ar2CN2 392f. 1,2,4-Trioxolanes 409 f. Triphosgene, see Bis(trichloromethyl) carbonate l,3,5-Tris(diazo)cyclohexane-2,4,6-trione 60 Tunnel effect - in electron transfer reactions of diazoalkanes 402 ~ i*1 reactions of carbenes 336 Umpolung 127, 392 Urea, as scavenger for HNO2 123 Urea derivatives, 7V-alkyl-7V-nitroso-, - carcinogenicity 30, 128, 129 - cytostatic effect 131 - as source for diazoalkane synthesis 28ff.. 50, 133, 246 Urethanes, see Carboxamides Vinyl carbenes, see Ethenyl carbenes Vinyl-a-diazo compounds, see Diazoalkenes 9

„ ,£ST2T , . Wolff-Kishner reduction 241 Wolff rearrangement - in diazo transfer reaction 51 ' hist °ry . 3>344j;> 357f' mechamsln ' 350ff ' *«?\cf ^ „34*> 348> 351> 357 - photolytic 346ff., 355 - products 345ff., 352ff. reviews 337 ~ theoretical investigations 351 f., 355ff. ,, , 344ff., ~> AAfC , c 1 r. - thermal 351 f. Woodward-Hoffmann rules 200,202

Xanthenylidene 309 Ynamines, diazo transfer to ynamines 75, 76 ff. Ynyl ethers, diazo transfer to ynyl ethers 75 ff.