Chemistry of Carbon Compounds: 2nd Supplement to 2r.e v.3B, C, D

Second Supplements to the 2nd Edition of RODD' S CHEMISTRY OF CARBON COMPOUNDS Second Supplements to the 2nd Edition...

Author: Malcolm Sainsbury

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Second Supplements to the 2nd Edition of

RODD' S CHEMISTRY OF CARBON COMPOUNDS

Second Supplements to the 2nd Edition of

RODD'S CHEMISTRY OF CARBON COMPOUNDS VOLUME I

ALIPHATIC COMPOUNDS ,k

VOLUME II

ALICYCLIC COMPOUNDS ~r

VOLUME III

AROMATIC COMPOUNDS ,k

VOLUME IV

HETEROCYCLIC COMPOUNDS

VOLUME V

MISCELLANEOUS GENERAL INDEX ,k

Second Supplements to the 2nd Edition of

RODD'S CHEMISTRY OF CARBON COMPOUNDS A modern comprehensive treatise Edited by M A L C O L M SAINSBURY

School of Chemistry, The University of Bath, Claverton Down, Bath BA2 7AY, England Second Supplement to VOLUME III AROMATIC C O M P O U N D S Part B: Benzoquinones and Related Compounds: Derivatives of Mononuclear Benzenoid Hydrocarbons with Nuclear Substituents Attached through an Element other than the Non-metals in Groups VI and VII of the Period Table Part C: Nuclear-substituted Benzenoid Hydrocarbons with more than one Nitrogen Atom in a Substituent Group Part D: Monobenzenoid and Phenolic Aralkyl Compounds, their Derivatives and Oxidation Products" Depsides, Tannins, Lignans, Lignin and Humic Acid (Partial" Chapter 12 in this volume)

1995 ELSEVIER Amsterdam - Lausanne - New York- Oxford-Shannon-Tokyo

ELSEVIER SCIENCE B.V. Sara Burgerhartstraat 25 EO. Box 211, 1000 AE Amsterdam, The Netherlands

ISBN: 0-444-82242-9

9 1995 ELSEVIER SCIENCE B.V. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior written permission of the publisher, Elsevier Science B.V., Copyright & Permissions Department, P.O. Box 521, 1000 AM Amsterdam, The Netherlands. Special regulations for readers in the U.S.A. - This publication has been registered with the Copyright Clearance Center Inc. (CCC), 222 Rosewood Drive Danvers, MA 01923. Information can be obtained from the CCC about conditions under which photocopies of parts of this publication may be made in the U.S.A. All other copyright questions, including photocopying outside of the U.S.A., should be referred to the copyright owner, Elsevier Science B.V., unless otherwise specified. No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. This book is printed on acid-free paper. Printed in The Netherlands.

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Contributors to this Volume J. MALCOLM BRUCE Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, U.K. S.M. FORTT School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, U.K. STEPHEN T. MULLINS Department of Chemistry, Brunel University, Uxbridge, Middlesex UB8 3PH, U.K. A.J. PEARSON Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-7078, U.S.A. MALCOLM SAINSBURY School of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, U.K. P.D. WOODGATE Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-7078, U.S.A.

vii

Preface to Volume III B/C/D (partial) This volume spans several very important areas of aromatic chemistry. It includes chapters devoted to benzoquinone, nitro compounds, metallo derivatives and aromatic hydrocarbons with substituents which contain more than one nitrogen atom, e.g., azobenzenes, azides, etc. The first chapter is written by Dr. Malcolm Bruce. It is fitting that I should recognise Dr. Bruce's special contribution to Rodd, since it was he who wrote on this subject in the 2nd edition in 1974 and again in the 1st Supplement. Dr. Bruce's enthusiasm and lifelong interest in this subject is still very evident, and this can easily be judged by the style with which he has surveyed progress in benzoquinone chemistry in the last decade. The application of organometallic chemistry to synthesis has been spectacular, and two chapters in this volume emphasise this development. With so much information, the task of condensing the most significant new knowledge into a readable and informative account is a daunting one. Yet the authors, Dr. Mullins and Professors Pearson and Woodgate, have managed this with skill and flair. Dr. Simon Fortt has written on the chemistry of the nitroarenes. This is a subject steeped in history, but it is still very much alive and relevant today as is highlighted in Dr. Fortt's contribution. I would like to thank all the authors for making my job as editor an easy and intellectually rewarding one. Malcolm Sainsbury

Bath March 1995

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ix

Contents Volume III B/C/D (partial)

A r o m a t i c Compounds: Benzoquinones a n d related compounds: Derivatives of mononuclear benzenoid hydrocarbons with n u c l e a r s u b s t i t u e n t s a t t a c h e d t h r o u g h an e l e m e n t othe r t h a n the n o n - m e t a l s in Groups VI and VII of the Periodic Table N u c l e a r - s u b s t i t u t e d benzenoid h y d r o c a r b o n s with more t h a n one nitrogen a t o m in a s u b s t i t u e n t group Monobenzenoid a n d phenolic a r a l k y l compounds, their derivatives a n d oxidation products: Depsides, tannins, lignans, lignin a n d h u m i c acid List of contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . List of common abbreviations a n d symbols used . . . . . . . . . . . . . . . . . . . . . . . .

vi vii xiii

Chapter 8. Benzoquinones and Related Compounds by J. M A L C O L M BRUCE 1. I n t r o d u c t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. O ve r vie w of quinone reactivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) Electron t r a n s f e r . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) Addition of nucleophiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) Cycloaddition reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (d) S u b s t i t u t i o n reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (e) P h o t o c h e m i s t r y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (f) Complexes a n d molecular assemblies . . . . . . . . . . . . . . . . . . . . . . . . . . (g) Ring f r a g m e n t a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. S y n t h e s i s of benzoquinones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) F r o m phenols and h y d r o q u i n o n e s and their ethers . . . . . . . . . . . . . . . . (b) F r o m cyclobutene-1, 2-diones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. B e nz oquinone m e t h i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) Overview of quinone m e t h i d e reactivity . . . . . . . . . . . . . . . . . . . . . . . . . (b) 1,2-Benzoquinone m e t h i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) 1, 4-Benzoquinone m e t h i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. Thiobenzoquinones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7. B e n z oquinone imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) 1, 2-Benzoquinone imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) 1, 4-Benzoquinone imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8. H o m o b e n z o q u i n o n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9. Benzoquinols (hydroxycyclohexadienones) . . . . . . . . . . . . . . . . . . . . . . . . . . (a) 1, 4-Benzoquinols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) 1, 2-Benzoquinols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) 1, 4-Benzoquinol imines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1 2 3 3 7 14 20 21 25 27 29 29 31 35 35 36 42 45 46 46 47 48 49 50 52 53

X

Chapter 9. Derivatives of Benzenoid Hydrocarbons with Substituents containing a single Nitrogen Atom by S.M. F O R T T 1. N i t r o d e r i v a t i v e s of benzene, its homologues a n d o t h e r s u b s t i t u t e d b e n z e n e s (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) O x i d a t i o n of a r o m a t i c a m i n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (c) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. N i t r o s o d e r i v a t i v e s of benzene a n d its homologues . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. N - A r y l h y d r o x y l a m i n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. N - A r y l n i t r o n e s a n d N - a r y l n i t r o x i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. A r o m a t i c a m i n e s derived from b e n z e n e and its homologues n u c l e a r p r i m a r y monoamines ................................................ (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. B e n z e n e d i a m i n e s a n d b e n z e n e t r i a m i n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7. N - S u b s t i t u t e d a r y l a m i n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8. N - A r y l a m i d e s (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9. N - A r y l i s o c y a n a t e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10. N - A r y l u r e a s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11. N - A r y l c a r b a m a t e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (b) P r o p e r t i e s a n d reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12. N - A r y l c a r b o d i i m i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13. N - A r y l i s o c y a n i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14. N - A r y l i s o t h i o c y a n a t e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15. N - A r y l a m i d e s of sulfur acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16. N - A r y l a m i d e s of p h o s p h o r u s acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

55 55 59 60 64 64 65 66 66 67 69 70 70 74 76 76 77 78 78 83 84 84 85 87 87 87 89 89 89 89 89 90 91 91 91 92 92

Chapter 10. Aromatic Compounds of the Non-Transition Metals by S T E P H E N T. M U L L I N S 1. I n t r o d u c t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. G r o u p 1 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 L i t h i u m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

95 95 95

xi 2.2 S o d i u m , p o t a s s i u m , r u b i d i u m , c a e s i u m . . . . . . . . . . . . . . . . . . . . . . . . . 3. G r o u p 2 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 B e r y l l i u m , m a g n e s i u m , calcium, s t r o n t i u m , b a r i u m . . . . . . . . . . . . . . . 3.2 Zinc, c a d m i u m a n d m e r c u r y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. G r o u p 3 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 B o r o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 A l u m i n i u m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. G r o u p 4 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Silicon a n d g e r m a n i u m . . . . . ................................ 5.2 T i n a n d lead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. G r o u p 5 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7. G r o u p 6 m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

109 112 112 117 123 123 126 128 128 139 145 149

Chapter 11. Aromatic Compounds of the Transition Elements by A.J. P E A R S O N A N D P.D. W O O D G A T E 1. I n t r o d u c t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. M a n g a n e s e , t e c h n e t i u m a n d r h e n i u m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 ~6 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 7/2 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 ~1 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Iron, r u t h e n i u m a n d o s m i u m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 ~6 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 ~2 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. C h r o m i u m , m o l y b d e n u m a n d t u n g s t e n . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 (~-Arene)Cr(CO)3 C o m p l e x e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (a) P r e p a r a t i o n s ............................................. (b) S t r u c t u r e of (rl~-arene) complexes: influence of the Cr(CO)3 group . . . . . (c) R e a c t i o n s of (~6-arene)Cr(CO)~ complexes . . . . . . . . . . . . . . . . . . . . . . . 4.2 Nucleophilic A d d i t i o n to t h e ~ - a r e n e ring . . . . . . . . . . . . . . . . . . . . . . (i) A d d i t i o n d i s p l a c e m e n t ; SNAr, 1 9 4 - (ii) Nucleophile a d d i t i o n - o x i d a t i o n , 1 9 7 - (iii) N u c l e o p h i l e a d d i t i o n - e l e c t r o p h i l e addition, 2 0 0 4.3 (~6-Arene)M(CO)3 complexes (M = Mo, W) . . . . . . . . . . . . . . . . . . . . . . . 5. O t h e r m e t a l s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

151 152 152 162 163 165 165 183 185 186 186 192 193 194

211 212

Chapter 12. Nuclear Substituted Benzenoid Hydrocarbons with more than one Nitrogen Atom in the Substituent by M A L C O L M S A I N S B U R Y 1. A r y l n i t r o s a m i n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 (i) S y n t h e s i s , 215 - (ii) Reactions, 216 2. A r y l d i a z e n e c a r b o n i t r i l e s (arylazo c y a n i d e s ) . . . . . . . . . . . . . . . . . . . . . . . . 216 3. A r y l a z o s u l p h i d e s a n d oxidised d e r i v a t i v e s . . . . . . . . . . . . . . . . . . . . . . . . . 216 (i) S y n t h e s i s , 2 1 6 - (ii) Reactions, 2 1 7 4. 2 - A l k y l - l - a r y l d i a z e n e s ( a r y l a z o a l k a n e s ) , 2 - a l k e n y l - l - a r y l d i a z e n e s (arylazoalkenes) and related compounds ................................. 219 (i) S y n t h e s i s , 219 - (ii) Reactions, 220 5. A r y l d i a z e n e oxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223

xii 6. A z o a r e n e s (1, 2 - d i a r y l d i a z e n e s ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224 (i) S y n t h e s i s , 2 2 4 - (ii) Reactions, 2 2 9 7. A z o x y a r e n e s (1, 2 - d i a r y l d i a z e n e N-oxides) . . . . . . . . . . . . . . . . . . . . . . . . . . 232 (i) S y n t h e s i s , 2 3 2 - (ii) Reactions, 2 3 4 8. A r e n e d i a z o n i u m salts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236 (i) S y n t h e s i s , 2 3 6 - (ii) Reactions, 2 3 8 9. A r y l h y d r a z i n e s a n d a r y l h y d r a z o n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256 (i) S y n t h e s i s ( a r y l h y d r a z i n e s ) , 256 - (ii) Reactions ( a r y l h y d r a z i n e s ) , 257 - (iii) P h y s i c a l p r o p e r t i e s ( a r y l h y d r a z o n e s ) , 260 - (iv) S y n t h e s i s ( a r y l h y d r a z o n e s ) , 261 - (v) C h e m i c a l reactions ( a r y l h y d r a z o n e s ) , 262 10. N - A r y l h y d r a z o n o y l h a l i d e s a n d a r y l n i t r i l i m i n e s (arylnitrile imides) . . . . . . 301 (i) S y n t h e s i s ( h y d r a z o n o y l halides), 3 0 1 - (ii) Reactions, 3 0 2 11. S u b s t i t u t e d a r y l h y d r a z i n e s a n d 1 , 2 - d i a r y l h y d r a z i n e s ( h y d r a z o b e n z e n e s ) . . 311 (i) S y n t h e s i s , 3 1 1 - (ii) Reactions, 3 1 3 12. F o r m a z a n s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 (i) S y n t h e s i s , 3 1 4 - (ii) Reactions a n d physical properties, 3 1 9 13. A r y l a z i d e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 (i) Reactions, 320 - (ii) U s e s in heterocyclic s y n t h e s e s , 322 14. A r y l t r i a z e n e s (diazoamino c o m p o u n d s ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 (i) Biological i m p o r t a n c e , 327 - (ii) Synthesis, 328 - (iii) Reactions, 333 15. H e x a z e n e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336 Guide to t h e i n d e x . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Index .........................................................

339 341

xiii

List of Common Abbreviations and Symbols Used

A /~ Ac a as, a s y m r n ,

at. B Bu b.p. c, C CD conc. D D D d dec., decomp deriv, E E l , E2 E lcB ESR Et e f.p. G GLC g H h Hz I IR J J K k kcal M Me rn m.p. Ms

acid ,~,lgstr6m units acetyl axial asymmetrical atmosphere base butyl boiling point concentration circular dichroism concentrated Debye unit, 1 x 10-is e.s.u. dissociation energy dextro-rotatory; dextro configuration density with decomposition derivative energy; extinction; electromeric effect uni- and bi-molecular elimination mechanisms unimolecular elimination in conjugate base electron spin resonance ethyl nuclear charge; equatorial freezing point free energy gas liquid chromatography spectroscopic splitting factor, 2.0023 applied magnetic field; heat content Planck's constant hertz spin quantum number; intensity; inductive effect infrared coupling constant in NMR spectra Joule dissociation constant Boltzmann constant; velocity constant kilocalories molecular weight; molar; mesomeric effect methyl mass; mole; molecule; m e t a melting point mesyl (methanesulphonyl)

xiv

N NMR NOE n

molecular rotation Avogadro number; normal nuclear magnetic resonance Nuclear Overhauser Effect normal; refractive index; principal quantum number

0

ortho-

ORD P Pr Ph P PMR R S

optical rotatory dispersion polarisation; probability; orbital state propyl phenyl para-; orbital proton magnetic resonance clockwise configuration counterclockwise configuration; entropy; net spin of incompleted electronic shells; orbital state uni- and bi-molecular nucleophilic substitution mechanism internal nucleophilic substitution mechanism symmetrical; orbital secondary solution symmetrical absolute temperature p-toluenesulphonyl triphenylmethyl time temperature (in degrees centrigrade) tertiary ultraviolet optical rotation (in water unless otherwise stated) specific optical rotation dielectric constant; extinction coefficient dipole moment; magnetic moment Bohr magneton microgram micrometer wavelength frequency; wave number magnetic; diamagnetic and paramagnetic susceptibilities dextrorotatory laevorotatory negative charge positive charge

S~I, Ss2 SNi S sec

soln. symm. T Tosyl Trityl t temp. tert UV O~

s

# PB #g #m A /J X, Xd, X~

(+) (-) +

Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds, Vol.III B, C,D(Partial), edited by M. Sainsbury 9 1995 Elsevier Science B.V. All rights reserved.

Chapter 8 BENZOQUINONES AND RELATED COMPOUNDS J. MALCOLM BRUCE 1.

Introduction

Chapter 8 of Volume III, Part B, of the First Supplement to the Second Edition of "Rodd's Chemistry of Carbon Compounds" covered the literature on benzoquinones and related compounds from early 1973 to mid-1979. The present Chapter contains, mainly, information published from then until mid-1994. Overall, this period has been one of consolidation, with earlier methods of synthesis being complemented by new ones, and modes of reaction being extended successfully to new systems, often of greater complexity than those used previously, thus further establishing the selectivity of oxidation of phenols, hydroquinones, and catechols, and the ability of the 1,2- and 1,4-benzoquinonoid moieties to behave as one-electron acceptors and as electrophiles, and, in cyclo-addition reactions, as both dienophiles and, for the 1,2-series, as heterodienes. Notable advances include a general method of synthesis of variously substituted quinones via thermal ring expansion of alkenyl- and alkynyl-cyclobutenolones (the former affording hydroquinones, which can be oxidised to benzoquinones, the latter benzoquinones directly), and a definitive study of the regiochemistry of nucleophilic substitution in 2-chloro-l,4-naphthoquinone, the results of which appear to be applicable to halogeno-1,4benzoquinones. New examples of the photochemistry of benzoquinones have continued to appear.

Benzoquinone methides and dimethides have attracted growing attention, particularly with respect to their applications in synthesis, especially in intramolecular Diels-Alder reactions, and to their roles in biological systems. 7,7,8,8-Tetracyano-1,4benzoquinone dimethide (TCNQ) and its congeners continue to be of interest for the preparation of electrically-conducting polymers, and the results have triggered interest in heterocyclic analogues (hetero-TCNQs) in which an endocyclic double bond of the sixmembered ring of the classical quinone methide system has been replaced by a hetero-atom, often sulfur. Improved procedures for the synthesis of benzoquinols (hydroxycyclohexadienones) have been developed, enabling the r01e of these compounds in synthetic methodology to be extended. 2.

Bibliography

Several major publications have appeared during the period under review, and together provide extensive coverage of a large part of it. "The Chemistry of the Quinonoid Compounds", Volume 2 (eds. S. Patai and Z. Rappoport, Wiley-lnterscience, Chichester, 1988) is in two parts, and totals 1711 pages. Part 1 deals with synthesis, analysis, spectroscopic properties, ground and excited state reactions, and electrochemistry. Part 2 covers radiation chemistry, quinhydrones and semiquinones, solid-state photochemistry, quinones as oxidants, quinone ketals and imines, and the biochemistry of quinones. "Naturally Occurring Quinones III, Recent Advances" (R.H. Thomson, Chapman and Hall, London, 1987) runs to 732 pages, of which the first 134 relate to benzoquinones. The same author devotes 12 pages to their synthesis in his Chapter "The Total Synthesis of Naturally Occurring Quinones" (in "The Total Synthesis of Natural Products", ed. J. ApSimon, Wiley, Chichester, 1992, Vol. 8, pp. 312 -531). Dopaquinone (a 1,2-benzoquinone) is an intermediate in the biosynthesis of melanins from tyrosine; research in this area has been reviewed in "Melanins and Melanogenesis" (G. Prota, Academic Press, San Diego, 1992). K.T. Finley's "Quinones: The Present State of Addition and Substitution Chemistry", originally scheduled to appear in the quinones "Update" volume of S. Patai's "The Chemistry of Functional Groups", has been published in "Supplement E: The

Chemistry of Hydroxyl, Ether and Peroxide Groups" (ed. S. Patai, Wiley, Chichester, 1993, Volume 2, Chapter 19, pp. 1027-1134). It covers addition and substitution by halogens and by nitrogen, oxygen, and sulfur nucleophiles, reactions at the carbonyl group(s), alkylation and acylation, cyclo-additions, including Diels-Alder and 1,3-dipolar cyclo-additions, and tandem reactions. Its inappropriate location notwithstanding, it provides an extensive review of the literature from 1983 to 1990. These publications, together with those cited in the present Series in Chapter 8 of Volume III, Part B, in the Second Edition, and in its First Supplement, highlight the development over the last 30 years of an extensive collection of reviews on quinone chemistry. The present Chapter supplements them in a selective, rather than an exhaustive, manner. 1

(a)

Overview of Quinone Reactivity

Electron Transfer

A characteristic of the quinonoid system is its ability to accept an electron, resulting in reduction to the corresponding semiquinone, an aromatic anion radical, viz (2) from 1,4benzoquinone (1), and (4) from 1,2-benzoquinone (3). Under comparable conditions, 1,2-benzoquinone is more readily reduced than 1,4-benzoquinone, a contributory factor being the

O

O~

o

oG

(1)

(2)

(3)

(4)

relief of dipolar and lone pair repulsions which are peculiar to the vicinal dione moiety in which rotation about the carbon-oxygen bond

is precluded (cf. A.R. Katritzky, et a/., J. Chem. Soc., Chem. Commun., 1990, 715). Electron-accepting substituents favour the reduction by stabilising the semiquinone. Donor substituents exert the opposite effect. This holds true in both solution and the gas phase, although in the gaseous state (P. Kebarle et al., J. Phys. Chem., 1986, 90, 2747; J. Am. Chem. Soc., 1988, 110, 400) the inductive effect of the oxygen atom of the methoxy group is markedly more important in stabilising the semiquinone than is the lone pair in conjugatively destabilising it. The reduction potentials of a variety of 2,5diaziridino-3,6-disubstituted-1,4-benzoquinones have been calculated to +50 mV using the COSMO continuum solvation model (H.S. Rzepa and G.A. SuSer, J. Chem. Soc., Chem. Commun., 1993, 1743); aziridino-1,4-benzoquinones are reductive bioalkylating agents, and show promise in cancer chemotherapy (Z.-D. Huang et a/., J. Med. Chem., 1993, 36, 1797). Addition of a further electron to the semiquinone to give the dianion (of the hydroquinone or catechol) is a higher energy process. Both one- and overall two-electron steps, denoted by E 11/2 and E21/2 respectively, can be quantified by cyclic voltammetry, conveniently using a glassy carbon electrode in an aprotic solvent, e.g. anhydrous dimethylformamide containing a supporting electrolyte such as tetrabutylammonium tetrafluoroborate. This technique provides corresponding data for the reverse (oxidation) process in which electrons are removed stepwise, one from the dianion to yield the semiquinone, the second from the semiquinone to regenerate the quinone (R.C. Prince et al., Methods Enzymol., 1986, 125, 109). The greater the electron affinity of the quinone, the more easily it effects oxidation/dehydrogenation of appropriate substrates. The high potential quinones 2,3-dichloro-5,6-dicyano1,4-benzoquinone (DDQ) (5) and tetrachloro-1,2-benzoquinone (6) (respectively E 11/2 +597 mV and +197 mV in dimethylformamide versus saturated calomel reference; cf. 1,4-benzoquinone, -401 mV) are frequently employed for this purpose. The distinction between electron and hydride transfer from substrate to oxidant is difficult to establish, and the precise mechanism may be governed by the medium in which the process occurs (cf. C Reichardt, "Solvents and Solvent Effects in Organic Chemistry", Second Edn, VCH, Weinheim, 1988; C.I.F. Watt, Adv. Phys. Org. Chem., 1988,

24, 57; J.W. Bunting, Bio-org. Chem., 1991, 19, 456; C.A. Coleman, J.G. Rose and C.J. Murray, J. Am. Chem. Soc., 1992, 114, 9755; J.-P. Cheng et al., J. Org. Chem., 1993, 58 5050). CI

O CI

~N

CI

N

CI

O

O

CI

(5)

(6)

Free energy hydride affinities (-AGH) in dimethyl sulfoxide for simple 1,2- and 1,4-benzoquinones range from 58 kcal mol-1 for tetramethyl-l,4-benzoquinone (duroquinone) to 101 kcal mol-1 for 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ); for chlorosubstituents, the effect of electronegativity dominates over that of lone pair polarisation (J.-P. Cheng et al., J. Org. Chem., 1993, 58

5050). Electron transfer to DDQ is likely to be the first step in each of the following cases where it is used for the cleavage of silyl ethers (K. Tanemura, T. Suzuki and T. Horaguchi, J. Chem. Soc., Perkin Trans. 1, 1992, 2997), acetals (K. Tanemura, T. Suzuki and T. Horaguchi, J. Chem. Soc., Chem. Commun., 1992, 979; A. Oku, M. Kinugasa and T. Kamada, Chem. Lett., 1993, 165), and dithioacetals (L. Mathew and S. Sankararaman, J. Org. Chem., 1993, 58, 7576). It is also likely to be involved in the oxidative polymerisation by DDQ of diphenyldisulfide to poly(p_-phenylene sulfide), (-C6H4S-)n (E. Tsuchida et al., Macromolecules, 1992, 25 2698); lower-potential benzoquinones also effect this polymerisation, but only in the presence of trifluoroacetic acid; electron transfer is then probably to the protonated quinone, which is a more effective acceptor (E. Tsuchida and K. Yamamoto, in J. Reedijk, ed., "Bioinorganic Catalysis", Marcel Dekker, New York, 1993, Chap. 4). Similarly, the arylation of 1,4-benzoquinones by aromatic hydrocarbons (the Pummerer reaction) requires the presence of a

Lewis acid, aluminium(lll) chloride, to complex with the quinone; arylation by phenols probably involves the aluminium phenolate also (G. Sartori et al., J. Chem. Soc., Perkin Trans. 1, 1993, 39; cf. H.-J. Kn61ker and N. O'Sullivan, Tetrahedron, 1994, 50 10893). Low potential quinones, such as 2,6-di-t-butyl-1,4benzoquinone, act as electron relays in the ruthenium(ll)-catalysed oxidation of secondary alcohols to ketones by cobalt complexes (G.-Z. Wang, U. Andreasson and J.-E. B&ckvall, J. Chem. Soc., Chem. Commun., 1994, 1037) and by manganese dioxide (U. Karlsson, G.-Z. Wang and J.-E. B&ckvall, J. Org. Chem., 1994, 59, 1196). At the other extreme of the redox potential scale are the benzoquinones which mediate electron transfer cascades in key bioprocesses such as photosynthesis, e.g. the ubiquinones (7) and the plastoquinones (8) [E 11/2 (n = 10) -602 mY, and (n = 9) -619 mV respectively], in these systems, changes in the number of

MeO

H n

MeO"-~r~-Me O (7)

Me

H

n Me" O (8)

isoprene units in the side-chain have relatively little effect on the reduction potential (R.C. Prince, P.L. Dutton and J.M. Bruce, FEBS Lett., 1983, 160, 273), although the side-chains play vital rSles in anchoring the quinones within photosynthetic reaction centres; the first three isoprene units are especially important (K. Warncke et al., Biochemistry, 1994, 33, 7830). Addition of an electron to a ubiquinone or to a plastoquinone produces the semiquinone, which can transfer a single electron to a neighbouring quinone, thus regenerating the initial quinone and enabling the stepwise transport of electrons to continue (G. Lenaz, ed., "Biochemistry, Bioenergetics, and Chemical Application of Ubiquinone", Wiley, Chichester, 1985; M. Iwaki and S. Itoh, in J.R.

Bolton, N. Mataga and G. McLendon, eds, "Electron Transfer in Inorganic, Organic, and Biological Systems", American Chemical Society, Washington, D.C., 1991, Chap. 10; B.L. Trumpower, "Function of Quinones in Energy Conserving Systems", Academic Press, New York, 1992; A. Labahn et al., J. Phys. Chem., 1994, 98, 3417). It is less likely that under biological conditions a second electron will be transferred to the semiquinone to afford the hydroquinone dianion in isolation. However, such a transfer becomes feasible within the hydrated protein network of the reaction centre, where electron transfer to the semiquinone may occur following, or concomitantly with, proton-abstraction involving, e.g. water, a feature which both results in proton transfer and highlights the r61e of the medium in controlling overall reactivity (J.M. Keske, J.M. Bruce and P.L. Dutton, Z. Naturforsch, 1990, 45c, 430; cf. T.H. Fife, Acc. Chem. Res., 1993, 26, 325). Examples of this aspect of the reactivity of quinones in vitro are cited elsewhere in this Chapter.

(b)

Addition of Nucleophiles

Nucleophilic addition is more complex than electron addition, and can lead to several types of product, the nature of which is dependent on the nucleophile, the counterion, and the medium. In general, soft nucleophiles give products of attack at alkenic carbon; hard nucleophiles afford products arising from addition to carbonyl carbon (M. Solomon et al., J. Am. Chem. Soc., 1988, 110, 3702). The latter process may be reversible unless the incipient oxyanion, or hydroxy group, is subsequently trapped, as in the formation of trimethylsilyl ethers (9) by reaction with trimethylsilyl cyanide in the presence of zinc(ll) iodide; treatment with fluoride ion regenerates the carbonyl group (D.A. Evans and R.Y. Wong, J. Org. Chem., 1977, 42,350). However, complexing of the quinone with the Lewis acid probably precedes or accompanies addition of the cyano moiety. Complexation of this type is also involved in other reactions which lead to attack at the ethenic double bond, e.g. allylation effected with allyltrimethylstannanes in the presence of boron(Ill) fluoride etherate, which affords the hydroquinone counterparts of the ubiquinones (7) (Y. Naruta and K. Maruyama, Org. Synth., 1993, 71,125).

NC

SiMe 3

OH

O SO3H

OH SO3H

SO2Ph

O

OH

OQ

OH

(9)

(10)

(11)

(12)

Hydrogen sulfite (HSO3-) adds reversibly to carbonyl carbon in 1,4-benzoquinone, but irreversibly to alkenic carbon to afford, ultimately, the sulfonic acid (10) (M.P. Youngblood, J. Org. Chem., 1986, 51, 1981). The irreversibility is a consequence of enolisation of the initial adduct (11) to give the (aromatic) hydroquinone. Overall, the quinonoid moiety is reduced following, in principle, a Michael addition (P. Perlmutter, "Conjugate Addition Reactions in Organic Synthesis", Pergamon, Oxford, 1992). If the ultimate objective is to obtain the quinone, e.g. a ubiquinone (7) resulting from prenylation, then the corresponding intermediate hydroquinone must be oxidised in a subsequent step. Since the hydroquinonesulfonic acids are troublesome to isolate, this type of nucleophilic addition is more conveniently studied using benzenesulfinic acid as the nucleophile, particularly under overall acidic conditions, affording the corresponding sulfone (12). These reactions are particularly clean because the initial quinone is incapable of oxidising the hydroquinone (12), and complicating redox equilibria are therefore avoided (e.g. Ell/2, vide supra, 1.4-benzoquinone,-401 mV; phenylsulfonyl-l,4benzoquinone, -40 mV). The effects of substituents carried by the quinone on the orientation of nucleophilic addition, which is essentiallygoverned by the criteria for Michael addition, can therefore be evaluated conveniently (J.M. Bruce and P. LloydWilliams, J. Chem. Soc., Perkin Trans. 1, 1992, 2877). Interestingly, consideration of electronic effects usually enables the position of nucleophilic attack to be predicted reliably; the predictions of molecular orbital calculations are generally in agreement (M.D. Rozeboom, I.-M. Tegmo-Larsson and K.N. Houk, J. Org. Chem. 1981, 46, 2338). Thus for monosubstituted 1,4-

benzoquinones (13), when R is an electron donor, the order of reactivity towards addition of the nucleophile is position 5 > 6 > 3, and when R is an acceptor, the order is 3 > 6 > 5 unless the system is otherwise perturbed by effects of the medium in which the reaction is performed. O

OH

R

O

SO2Ph

O

OH

(13)

(14)

O

i ~

O

~]} O (15)

Reactions with sulfinic acids are frequently effected in aqueous media, with the fairly readily oxidised sulfinic acid being generated in situ from its sodium salt. The medium is therefore acidic. According to prediction, acetyl-l,4-benzoquinone (13; R = COMe) affords the hydroquinone (14)in high yield (J.M. Bruce and P. Lloyd-Williams, J. Chem. Soc., Perkin Trans. 1, 1992, 2877). The xanthone-1,4-quinone (15) can be regarded as a vicdisubstituted-1,4-benzoquinone in which the lone pair from the oxygen atom in the ring is delocalised on to the peri carbonyl groups, thus devolving control of the position of nucleophilic addition to the 4-carbonyl moiety. Michael addition at the 2-position would therefore be expected. Under the usual experimental conditions (the quinone in dichloromethane shaken with aqueous sodium benzenesulfinate acidified with trifluoroacetic acid) the hydroquinone (16) is formed almost exclusively, indicating that the quinone is protonated between the carbonyl groups (as 17) prior to reaction with the sulfinic acid; the protonated 1-carbonyl group thus controls the regiochemistry of the Michael addition (J.M. Bruce and I.M. Farhat, unpublished work). In this example, protonation under mild conditions is particularly favourable because it removes lone pair-lone pair repulsion between the peri carbonyl groups (cf. A.R. Katritzky et al., J. Chem. Soc., Chem. Commun., 1990, 715). Nonetheless, it serves to illustrate the dramatic effect which the medium can exert

]0 on the outcome of the reaction. Thus protonation, and, equivalently, Lewis-acid complexation, can play a dominant r61e in controlling the reactivity of even simple quinones towards nucleophiles. The phenomenon is in no way unexpected: it is a particular example of the chemistry of the carbonyi group. Further examples, including nucleophiles other than those which are sulfurbased, are given in the sequel.

O

OH

O

~,,,~ L . SO2Ph OH

O

O

(16)

(17)

Due to their relative instability, simple 1,2-benzoquinones have been less extensively studied, although, overall, vinylogous Michael [1,6-] addition is preferred, perhaps reflecting the extent of stabilisation in the formal intermediate: addition of the nucleophile (Nu-) at a position adjacent to a carbonyl group leads to the maximally (cross) conjugated enolate (18), in contrast to the enolate (19) which would be the result of formal 1,4-addition. Protonation and enolisation of (18) then leads to the 3-substituted catechol (cf. D.J. Liberato et al., J. Med. Chem., 1981, 24, 28).

Nu_CX oOo Nu H (18)

H (19)

]! The highly reactive dopaquinone is a key intermediate in melanogenesis, and undergoes both intermolecular addition of, particularly, thiols, and intramolecular addition (i.e. cyclisation) to yield, subsequently, 5,6-dihydroxyindole and related species (G. Prota, "Melanins and Melanogenesis", Academic Press, San Diego, 1992; R.V. Bensasson, E.J. Land and T.G. Truscott, "Excited States and Free Radicals in Biology and Medicine", Oxford Science Publications, Oxford, 1993, Chap. 8). Of the more stable 1,2-benzoquinones, the reactions of 3-tbutyl- (20) and, particularly, 3,5-di-t-butyl-l,2-benzoquinone (21) have been studied to a greater extent. Whilst the 3-t-butyl compound allows for addition to occur at positions 5- and/or 6-, all nuclear positions other than the 1-carbonyl carbon in the di-tbutylquinone are extensively shielded by the bulk of the t-butyl groups, with the result that reactions at oxygen (e.g. heterodiene addition: see below) have been highlighted. 4,5-Dialkoxy-l,2-benzoquinones, e.g. (22), are comparatively stable, but behave atypically from the parent: the two adjacent vinylogous ester moieties are responsible, and may direct addition reactions to the carbonyl groups (e.g. organolithium reagents: K.F. West and H.W. Moore, J. Org. Chem., 1982, 47, 3591), although vinylogous amides, e.g. (23), result from reaction with amines (Z.-D. Huang et al., J. Med. Chem., 1993, 36, 1797).

{ ~ O O

M e O ~ O MeO" ~

(20)

(21)

MeO~O CICH2CH2NH"

~ (23)

"O

"O

(22)

]2 Formation of a semiquinone from a quinone involves single electron transfer. However, although nucleophilic addition has been shown in the foregoing examples as a two-electron (polar) process, bond formation and breaking may occur via successive singleelectron transfer steps (S.S. Shaik, Progr. Phys. Org. Chem., 1985, 1.5, 197; A. Pross, J. Am. Chem. Soc., 1986, 10.8.,3537; E.C. Ashby, Acc. Chem. Res., 1988, 24, 414; J.-M. Sav~ant, Acc. Chem. Res., 1993, 2__66,455) in which the semiquinone would be implicated as a transient intermediate, with the nucleophile becoming, again transiently, a 'free' radical. However, intervention of the semiquinone per s_eeseems unlikely, since the radical-radical combination which would ensue in order to form the nucleophilecarbon bond in the initial adduct, e.g. (18), would have to be sufficiently energetic to overcome the aromaticity of the semiquinone. Transfer of the two electrons is thus likely to be virtually simultaneous, and the process becomes formally analogous to a classical Michael addition (S. Hoz, Acc. Chem. Res., 1993, 26, 69; P. Perlmutter, "Conjugate Addition Reactions in Organic Synthesis", Pergamon, Oxford, 1992; A. Pross, in J.M. Harris and S.P. McManus, eds, "Nucleophilicity", American Chemical Society, Washington, D.C., 1987, Chap. 23). Readily polarised nucleophiles such as enamines (e.g. CH2=CH.NR2) add readily to quinones, usually via a deeplycoloured ~-complex. The arguments of the previous paragraph concerning mechanism then apply" semiquinone and cation radical (as 24) versus zwitterion (25) formed directly, this then collapsing by proton-loss, as shown, to afford the dihydrobenzofuran (26).

OQ

O (~

IL

OH

+.

Oo (24)

NR2

~(~ O (25)

(~NR2

NR2 (26)

]3 The corresponding vinyl ethers (CH2=CH.OR) and ketene acetals [CH2=C(OR)2] are usually insufficiently reactive for the corresponding addition to occur 'spontaneously'; prior protonation, or Lewis-acid complexation, at quinonoid oxygen is a prerequisite [protonated quinones are potent oxidents, i.e. electron-acceptors (O. Hammerich and V.D. Parker, Acta Chem. Scand., B, 1982, 36, 63)]. Similarly, phenols add to the 3-position of 2-acyl-l,4benzoquinones in the presence of trifluoroacetic acid, protonation at the oxygens of both the acyl group and the 1-carbonyl group of the quinone providing the driving force (P. Kuser et al., Helv. Chim. Acta, 1971,54, 980). Overall, a complement of electrophilicity (the quinone) and nucleophilicity (the substrate) is required, and can be achieved via either of the components. Control by the former is well-illustrated by the regiospecific addition to the 3- position of acetyl-1,4benzoquinones of silyl vinyl ethers (M.A. Brimble, M.T. Brimble and J.J. Gibson, J. Chem. Soc., Perkin Trans. 1, 1989, 179; G.A. Kraus et al., J. Org. Chem., 1990, 55, 1105; 1990, 55, 4922). The r61e of single electron transfer, developed for other systems (cf. A. Pross, Acc. Chem. Res., 1985, 18, 212; E.C. Ashby, Acc. Chem. Res., 1988, 21,414) remains to be established. The diversity of quinonoid systems available for study may in due course lead to a fuller understanding of the factors which control these reactions, ranging from the extremes of single electron transfer and electron pair transfer to a continuum of reactivity governed by the redox chemistry of the reactants and the nature of the environment in which the reaction occurs. Formal addition to the quinonoid nucleus, and its consequences, is well exemplified by the reaction of 1,4benzoquinone with chlorine in diethyl ether: the 2,3-dichloro-adduct (27) is formed in high yield. Enolisation with hydrogen chloride in dry diethyl ether affords the corresponding hydroquinone (28) (J.Y. Savoie and P. Brassard, Can. J. Chem., 1966, 44, 2867). However, when the enolisation is effected with concentrated hydrochloric acid in acetone, the isomeric 2,5-dichlorohydroquinone (29) is formed in high yield, possibly via elimination of hydrogen chloride to afford chloro-1,4-benzoquinone and subsequent readdition-enolisation (J.M. Bruce and P. Marshall, unpublished work).

]4 O

(c)

OH

OH

c,

CI

CI

CI

CI CI

O

OH

OH

(27)

(28)

(29)

Cycloaddition Reactions

Diels-Alder additions to 1,4-benzoquinones have been studied extensively. 1,3-Butadiene and its simple congeners afford 1:1 adducts (30) and, under more forcing conditions, especially in media of low polarity, bis-adducts (31). In more polar media, or at high temperature, the initial adduct may enolise to afford the corresponding hydroquinone (32). Complications then ensue because this hydroquinone carries two electron-donating alkyl substituents, and is oxidised to the corresponding quinone (33) by unreacted 1,4-benzoquinone, which is reduced to the hydroquinone concomitantly. This process is redox driven, e.g. Ell/2: 1,4benzoquinone,-401 mV; 2,3-dimethyl-l,4-benzoquinone,-543 mY. O

O

OH R

O

O (30)

(31)

OH (32)

Further dehydrogenation of (33) to the 1,4-naphthoquinone (34) may ensue [cf. R.T. Brown eta/., J. Chem. Res. (S), 1994, 220], with the formation of more hydroquinone. This forms the

].5 deeply coloured quinhydrone (the 1:1 1,4-benzoquinone hydroquinone complex) and mixed quinhydrones with the newly formed quinones (33) and (34). Complex mixtures thus result. Appropriate attention to experimental conditions, particularly the choice of solvent, can minimise or eliminate these side-reactions. Bis-adducts (31) are usually unaffected. O

O R

O

R O

(33)

(34)

Under kinetic control, the addition is endo, readily established for the addition of cyclopentadiene which, with 1,4benzoquinone, affords (35); the bis-adduct is endo-anti-endo (36) (R. Brown et al., J. Chem. Soc., Perkin Trans. 2, 1974, 132). Although the mono-adduct (35) can be enolised, more forcing conditions are required than those needed for enolisation of the non-bridged analogues (30): a norbornadiene is formed from (35). In consequence, additions involving cyclopentadiene usually occur cleanly. O

O

O

O (35)

(36)

]6 Addition of cyclopentadiene to methyl-1,4-benzoquinone (toluquinone) in ether affords the endo mono-adduct at the unsubstituted enone moiety, in high yield. The presence of lithium perchlorate leads to the formation of the corresponding endo-antiendo adduct, but, unusually, accompanied by about 15% of the endo-anti-exo isomer (P.A. Grieco et al., J. Am. Chem. Soc., 1990, 112, 4595). Complications due to enolisation of the initial 1:1 adduct are precluded by a substituent at the ring junction. These adducts are formed from, e.g., 2,5- and 2,6-disubstituted 1,4-benzoquinones. Those carrying a methoxy group provide clear exemplification of the r61e of complexation with Lewis acids. Thus 2-methoxy-5-methyl1,4-benzoquinone and 1,3-pentadiene afford a 1:1 mixture of the adducts (37) and (38) in the absence of Lewis acid, whereas (37) predominates in the presence of tin(IV) chloride, and (38)is the major product when boron(Ill) fluoride is used. The former may complex with the oxygens of the 1-carbonyl and the methoxy groups, whilst the latter may bind selectively t5 the 4-carbonyl group (J.S. Tau and W. Reusch, J. Org. Chem., 1980, 45, 5012). O

MeO

O

. H. ~ O (37)

MeO

H O (38)

2,3-Dichloro-5,6-dicyano-l,4-benzoquinone (DDQ, 5) reacts with cyclopentadiene in cold benzene to afford the expected endoadduct (39), the electron-accepting cyano groups controlling the regiochemistry of the addition. At reflux, the adduct (39) undergoes dissociation-recombination to give the thermodynamically-favoured isomeric exo-adduct (40). Both reactions are quantitative (J.M. Bruce and H. Finch, unpublished work). Clean endo-exo transformations of this type are, inevitably, rare in the Diels-Alder chemistry of benzoquinones.

]7 O CI

CN

CI

CI

O C N

CI

CN

O

O (39)

(40)

Strongly electron-accepting substituents dominate in controlling the regiochemistry of Diels-Alder additions. Thus acyl- and aroyl-, cyano, arylsulfonyl- and nitro-l,4-benzo-quinones (41; X as specified) afford the corresponding 1,3-pentadiene adducts (42) in high yield. Treatment of the acyl and aroyl compounds (42; X = COAIk, COAr) with organic bases such as pyridine result in enolisation, to (43), and subsequent [1,5] migration of X to yield the corresponding acyl- and aroyl-hydroquinones (44; R = AIk, Ar) (J.M. Bruce et al., J. Chem. Soc., Chem. Commun., 1981, 166, 169, 171; 1982, 686; S.C. Cooper and P.G. Sammes, J. Chem. Soc., Perkin Trans. 1, 1984, 2407 ).

,(

o x

O

o

O

(41)

OH (42)

O

OH

OH (44)

=

(43) O

-

O (45)

]8 When the substituent, X, is a good leaving group (CN, SO2Ar, NO2), similar treatment leads to elimination, probably via the enol (43), and formation of the corresponding 5,8-dihydro-1,4naphthoquinone (45) (cf. J.M. Bruce and P. Lloyd-Williams, J. Chem. Soc., Perkin Trans. 1, 1992, 2877). Recently, there has been a renewal of interest in the DielsAlder reaction of 1,4-benzoquinones (46) with substituted styrenes (47), which, although it requires forcing conditions, provides a useful synthesis of 1,4-phenanthraquinones (48). An excess of the benzoquinone is employed in order to oxidise the initial adduct, via its bis-enol (the corresponding hydroquinone), to the phenanthraquinone (N.D. Willmore, L. Liu and T.J. Katz, Angew. Chem., Internat. Ed. Engl., 1992, 31, 1093; A.B. Padias, T.-P. Tien and H.K. Hall, J. Org. Chem., 1991,56, 5540; L. Liu and T.J. Katz, Tetrahedron Lett., 1990, 31, 3983). O ii/JJ~~]

O a2

R2 R 1--;-~,

R1--~[,[

R3 R3

0 (46)

(47)

(48)

Interestingly, [2 + 2] additions, previously in the province of excited state (photo) chemistry, can be effected in the presence of titanium(IV). Thus methoxy-l,4-benzoquinone and (E)propenylbenzene in the presence of a mixture of titanium(IV) chloride and titanium(IV) isopropoxide yield, inter alia, the adduct (49) (T.A. Engler, K.D. Kombrink and J.E. Ray, J. Am. Chem. Soc., 1988, 110, 7931). Under similar conditions, benzyloxy-1,4benzoquinone and 7-methoxy-2H-chromene probably afford the corresponding [2 + 2] adduct (50), transiently: it isomerises to the pterocarpan system (51), providing a novel entry to this series of compounds (T.A. Engler, K.D. Combrink and J.P. Reddy, J. Chem. Soc., Chem. Commun., 1989, 454).

]9 O

O MeO

~~,~OMe

BnO.v~

h

O

H

0

(49)

(5o) OH BnO

o-7( `

(51)

o

OMe

Studies of the Diels-Alder chemistry of 1,2-benzoquinones have been much less extensive, to some extent as a consequence of the lower stability of the 1,2-quinones. However, even those carrying electron-accepting groups afford the expected Diels-Alder adducts when the quinones are generated in situ by oxidation of the corresponding catechols (R. AI-Hamdani and B. Ali, J. Chem. Soc., Chem. Commun., 1978, 397; D. Pitea et al., J. Org. Chem., 1985, 50, 1853; J. Lee, H.S. Mei and J.K. Snyder, J. Org. Chem., 1990, 55, 5013). Addition of the diene to monoalkyl-l,2-benzoquinones occurs at the least-substituted enone moiety (S. Knapp and S. Sharma, J. Org. Chem., 1985, 50, 4996). 1,2-Benzoquinones can also behave as heterodienes (D.L. Boger and S.M. Weinreb, "Hetero-Diels-Alder Methodology in Organic Synthesis", Academic Press, San Diego, 1987, pp. 167213; T.-L. Ho, "Polarity Control for Synthesis", Wiley, New York, 1991, pp 224-231), especially via inverse electron-demand. Thus, 4-t-butyl-1,2-benzoquinone reacts readily with the enamine (52) to afford the dihydrodioxin (53) (Y. Omote, A. Tomotake and C.

20 Kashima, J. Chem. Soc., Perkin Trans. 1, 1988, 151), whilst 3,5-dit-butyl-1,2-benzoquinone reacts, under more forcing conditions, with a variety of acyclic 1,3-dienes to produce adducts analogous to (54) (V. Nair and S. Kumar, J. Chem. Soc., Chem. Commun., 1994, 1341).

Cj (52)

(53)

H

1

R2

(54) (d)

Substitution Reactions

Studies of the nucleophilic displacement of chlorine from 2[13C].2_chloro_ 1,4-naphthoquinone highlight two addition-elimination mechanisms which have important regiochemical consequences for parallel substitutions in 1,4-benzoquinones (55) where X is the leaving group. Ipso attack, as (56), leads to substitution at the centre carrying the leaving group, whereas vicinal attack, as (57), followed by isomerisation to (58), results in attachment of the nucleophile (Nu-) at the adjacent alkenyl carbon. Attack by hard nucleophiles is predominantly ipso, and that by soft nucleophiles is exclusively vicinal; amines are borderline in reactivity, but ipso attack is favoured in polar media, whereas vicinal attack predominates in solvents of low polarity (D.W. Cameron, P.J. Chalmers and G.I. Feutrill, Tetrahedron Lett., 1984, 25, 6031).

2] These observations must be taken into account in rationalising the substitution chemistry of 1,4-benzoquinones, especially that described in the older literature.

o

,1~].[I ~ X

('c3

o

R--

o--

X~-Nu

R

o

~~r,.x

R-~~

R

xJ~H

Nu o

(55)

Nu

o

(56)

(57)

(58)

Displacement of leaving groups, particularly methoxy, from the 4- position of 1,2-benzoquinones appears to occur via ipsosubstitution, although yields are not high (Z.-D. Huang et al., J. Med. Chem., 1993, 36, 1797).

(e)

Photochemistry

Since quinones are coloured, much of their photochemistry, including that involved in photosynthesis, can be explored using visible light. Hydrogen-abstraction from the formyl group of aldehydes by excited 1,4-benzoquinones is particularly clean, the resulting acyl or aroyl radicals being scavenged by ground-state quinone either at the alkene moiety to yield, ultimately, the corresponding acyl- or aroyl-hydroquinone, or at oxygen to afford the mono-ester. The latter predominates with high-potential quinones, and has been explained in terms of initial electron transfer from the radical to the quinone in its ground state. Cyclodimerisation of 1,4-benzoquinones to afford cyclobutanes is common, whilst [2 + 2] cyclo-addition of alkenes can occur at both the ethene moiety, affording cyclobutanes, and the carbonyl group, affording spiro-oxetanes. Cyclo-addition of alkenes to photoexcited 1,2-benzoquinones occurs in the [4 + 2] mode, giving dihydrodioxins. Hydrogen-abstraction from, and fragmentation and

22 cyclisation involving, side-chains of 1,4-benzoquinones can occur. These aspects have been reviewed (J.M. Bruce, in S. Patai, ed., "The Chemistry of the Quinonoid Compounds", Wiley, l-ondon, 1974, Chap. 9; K. Maruyama and A. Osuka, in S. Patai and Z. Rappoport, eds., "The Chemistry of the Quinonoid Compounds", Vol. 2, Wiley, London, 1988, Chap. 13). Electron transfer from metalloporphyrins to triplet 1,4benzoquinone (S. Yamauchi et al., J. Photochem. Photobiol. A: Chem., 1992, 65, 177; M.N. Paddon-Row, Acc. Chem. Res., 1994, 27, 18) and from thianthrene to the triplets of 2,5-dichloro- and tetrachloro-l,4-benzoquinone (G. Jones, B. Huang and S.F. Griffin, J. Org. Chem., 1993, 58, 2035; see also G. Jones and B. Huang, Tetrahedron Lett., 1993, 34, 269; M.M. Ayad, Spectrochim. Acta, A, 1994, 50, 671) affords the corresponding substrate cation radicals and semiquinones. Similar electron transfer occurs from N,Ndimethylaniline and from triphenylamine to excited 1,4benzoquinone and duroquinone (tetramethyl-1,4-benzoquinone), and has been studied by CIDNP (N.E. Polyakov and T.V. Leshina, J. Photochem. Photobioi. A: Chem., 1990, 55, 43), and from tbutyldimethylamine to 2,5-dichloro-1,4-benzoquinone in sunlight (Zhong-Li Liu et al., J. Chem. Soc., Chem. Commun., 1991, 1054), which results in the formation of aryloxy-1,4-benzoquinones. CIDNP has also been used to establish that photo-excited 1,4-benzoquinone can function as a mediator of electron transfer from 1,4-dimethoxynaphthalenes as donors to 1', l'-dicyanomethylenecyclohexane as the ultimate acceptor (Y.-C. Liu et al., J. Photochem. Photobiol. A: Chem., 1992, 67 279). The quantum yield for formation of triplet 1,4-benzoquinone is high in solvents of low polarity, but decreases progressively as the polarity of the medium is increased; intermolecular electron transfer eventually predominates (R. Marquardt, S. Grandjean and R. Bonneau, Photochem. Photobiol. A: Chem., 1992, 69, 143). Analogous, intramolecular, processes occur in systems containing 1,4-benzoquinones linked to porphyrin moieties (Z.-M. Liu, W.-Z. Feng and H.-K. Leung, J. Chem. Soc., Chem. Commun., 1991,209; J.R. Bolton et ai., in J.R. Bolton, N. Mataga and G. McLendon, eds, "Electron Transfer in Inorganic, Organic, and Biological Systems", American Chemical Society, Washington, D.C., 1991, Chap. 7; M.R. Wasielewski, Chem. Rev., 1992, 92, 435; D. Gust, T.A. Moore and A.L. Moore, Acc. Chem. Res., 1993,

23 26, 198; H. Grennberg, S. Faizon and J.-E. B&ckvall, Angew. Chem. Int. Ed. Engl., 1993, 32 263; H.A. Staab et al., Chem. Ber., 1994, 127, 231; Angew. Chem. Int. Ed. Engl., 1994, 33, 1463; L. Sun et al., Angew. Chem. Int. Ed. Engl., 1994, 33, 2318). Irradiation of the 1,4-benzoquinone-di-aquabridged [Mn(N,N'3,5-dichlorosalicylidene-1,2-diaminoethane)(H20)2]2 complex with visible light results in photolysis of water, with evolution of oxygen (N. Aurangzeb et al., J. Chem. Soc., Chem. Commun., 1994, 1153). Photoreduction of 1,4-benzoquinone by electron transfer from porphyrin - ~-cyclodextrin systems has been studied (Y. Kuroda et al., J. Am. Chem. Soc., 1993, 115, 7003), and the synthetical usefulness of the formation of acylhydroquinones from photo-excited 1,4-benzoquinones and aldehydes (vide supra) has been re-examined, in particular as an alternative to the classical FriedeI-Crafts acylation of aromatic compounds (G.A. Kraus and M. Kirihara, J. Org. Chem., 1992, 57, 3256). Triplet tetramethyl- and tetrachloro-1,4-benzoquinone cause cleavage of O-O, C-C, and o~-C-H bonds in hydroperoxides such as PhCHMe.OOH, whereas triplet 2,3-dichloro-5,6-dicyano-l,4benzoquinone (DDQ) abstracts o~-C-H exclusively (G. M6ger and M. Gy6r, J. Photochem. Photobiol. A: Chem., 1991,59, 37). In some respects analogously, irradiation of a benzene solution of 1,4benzoquinone containing benzyl phenyl ether leads to the acetal (59), together with phenol and benzaldehyde (J.H. Penn et al., J. Org. Chem., 1994, 59, 3037). Similarly, irradiation of tetrachloro1,4-benzoquinone (chloranil) in the presence of the aziridine (60) and water in dichloromethane results in the formation of benzaldehyde and the Schiff's base PhCH=N.CH2Ph, in high yield (E. Hasegawa et al., J. Org. Chem., 1992, 57, 6342); the fragmentation may be initiated by single-electron transfer from aziridine nitrogen to the excited quinone. Proof of the anti head-to-tail structure (61) of the solid state [2 + 2] photodimer of 2-isopropyl-5-methyl-1,4-benzoquinone (thymoquinone) has been presented (R.J. Robbins and D.E. Falvey, Tetrahedron Lett., 1993, 34, 3509), and rates and stereochemistry of [2 + 2] spiro-oxetane formation from excited 1,4-benzoquinone and alkenes has been studied (D. Bryce-Smith et al., J. Chem. Soc., Perkin Trans., 2, 1991, 1587; cf. K. Maruyama and H. Imahori, J. Chem. Soc., Perkin Trans. 2, 1990, 257).

24 OPh

O

r

Ph

CH2Ph _

O

H O

N

Ph"" / \ "~Ph

I

I

OH

O

(59)

(60)

(61)

Phenylcyciopropane is a good electron-donor, and quenches triplet chloranil: in methanol, the product (62) of ionic cleavage is formed in high yield; irt dichloromethane, [2 + 3] cycloaddition occurs to afford the spiro-tetrahydrofuran (63) (Y. Takahashi et al., J. Chem. Soc., Chem. Commun., 1994, 1127). Ph O.,'L,,v-'~OMe o

CI

CI

ph

CI

CI

OH

0

(62)

(63)

A photo-[2 + 3] cycloaddition of potential generality is the formation of 2,3-dihydrobenzofurans (as 64) when mixtures of hydroxy-1,4-benzoquinones and alkenes are irradiated in acetone; the hydroquinones (64) are readily oxidised, in air, to the corresponding quinones (K. Kobayashi, Y. Kanno and H. Suginome, J. Chem. Soc., Perkin Trans. 1, 1993, 1449). Dihydroisosilabenzofurans, e.g. (65), are formed quantitatively when the corresponding disilanylquinone (66) is irradiated with visible light in hexane containing acetone, benzophenone or fluorenone

25 (H. Sakurai, J. Abe and K. Sakamoto, J. Photochem. Photobiol. A: Chem., 1992, 65, 111).

OH

O"SiMe3 ,,~

O

S[Me2

,7

R

OH

SiMe 3 I SiMe 2

O

(64)

(65)

(66)

Remarkably, the stereochemistry of the classical endo [4 + 2] Diels-Alder addition of cyclopentadiene to 1,4-benzoquinone and to toluquinone, giving the respective mono-adducts (67; R = H, Me), is inverted, giving the corresponding adducts (68; R = H, Me) with greater than 98% exo selectivity when the reaction is effected by irradiation at 300 nm in dry ethanol containing triethylamine; the mechanism has not been established (B. Pandey and P.V. Dalvi, Angew. Chem., Int. Ed. Engl., 1993, 32_ 1612). O

H

0

H

0

(67) (f)

O

(68)

Complexes and Molecular Assemblies

In the crystal, methoxy-1,4-benzoquinone is networked into a planar hexagonal array by intermolecular dipole-dipole and

26 extensive CH.-.O hydrogen bond interactions; one hydrogen of the methyl group, the three alkene hydrogens, and the three oxygen atoms are involved in hydrogen bonding (E.M.D. Keegstra et a/., J. Chem. Soc., Chem. Commun., 1994, 1633). Steady-state and transient absorption spectra of solid quinhydrones (1 "1 complexes between 1,4-benzoquinones and hydroquinones) have been shown to be dependent on the method of preparation of the crystals (K.K. Kalninsh et al., J. Photochem. Photobiol. A: Chem., 1994, 77. 9). The 'quinhydrone' between 1,4benzoquinone and 4,4'-dihydroxydiphenyldisulfide forms black crystals containing parallel chains of alternating quinone-phenol moieties linked by carbonyl-hydroxy hydrogen bonds (K. Sugiura et a/., Angew. Chem. Int. Ed. Engl., 1992, 3.j.1,852). The properties of covalently bound cage structures involving quinones and hydroquinones have been summarised as part of a wider review of "super" phanes (R. Gleiter and D. Kratz, Acc. Chem. Res., 1993, 2_.66,311). Macrocyclic bolaphiles containing two 1,4-benzoquinone units linked at their 2- and 5- positions have been employed to incorporate the quinonoid moieties into membrane systems, thus generating redox-active regions within the membranes (J.-H. Fuhrhop and M. Krull, in H.-J. Schneider and H. DQrr, eds, "Frontiers in Supramolecular Organic Chemistry and Photochemistry", VCH, Weinheim, 1991, pp. 223-249; G.H. Escamilla and G.R. Newcombe, Angew. Chem. Int. Ed. Engl., 1994, 3_33,1937). These systems are related to naturally occurring ones in which electron-storage and electron-transfer occur, such as enzymes and photosynthetic reaction centres where substituted 1,4-benzoquinone moieties play a key r61e (M. Iwaki and S. Itoh, in J.R. Bolton, N. Mataga and G. McLendon, eds, "Electron Transfer in Inorganic, Organic, and Biological Systems", American Chemical Society, Washington, D.C., 1991, Chap. 10; J.A. Duine and J.A. Jongejan, in J. Reedijk, ed., "Bioinorganic Catalysis", Marcel Dekker, New York, 1993; M. Baumgarten, W. Huber and K. MQllen, Adv. Phys. Org. Chem., 1993, 2_88,1; A. Labahn et al., J. Phys. Chem., 1994, 9__68,3417; K. Warnke et al., Biochemistry, 1994, 3,3, 7830). A range of macrocycles has been synthesised which contain cavities into which 1,4-benzoquinones can be incorporated, and

2"7 held in place by hydrogen bonding to each of the carbonyl oxygen atoms (C.A. Hunter et al., J. Am. Chem. Soc., 1992, 114, 5303; J. Chem. Soc., Chem. Commun., 1994, 1277; Chem. Soc. Rev., 1994, 2,3, 101). 1,4-Benzoquinones carrying polyether bridges linking the 2,6- positions have been described (M. Delgado et al., J. Am. Chem. Soc., 1992, 114, 8983). Monolayers prepared by reaction of gold surfaces with 11mercaptoundecanoic acid incorporate 2,2",4,4"-tetramethyl-4,4"diphenoquinone, which under electrochemical conditions can be redox cycled in situ with its hydroquinone, 2,2",4,4"-tetramethyl-4,4"dihydroxybiphenyl (M. Kunitake eta/., J. Chem. Soc., Chem. Commun., 1994, 563; see also C. Duschl, M. Liley and H. Vogel, Angew. Chem. Int. Ed. Eng., 1994, 3,3, 1274; A. Badia, R. Back and R.B. Lennox, Angew. Chem. Int. Ed. Engl., 1994, 3,3, 2332). Monolayers of substituted 1,4-benzoquinones result when a side-chain terminates in a thiol group through which binding to a gold surface can occur (J.J. Hickman et al., Science, 1991,2..52, 688).

(g)

Ring Fragmentation

Contraction of the 1,4-benzoquinone ring occurs when the quinone is treated with 4-nitrophenylazide" the enamine (69) is formed (I.T. Barnish and M.S. Gibson, J. Chem. Res. (S), 1992, 208; (M), 1740-1757). Extensive reorganisation takes place when the 3-azido-1,2-benzoquinone (70) is themolysed in boiling benzene, affording, possibly via a benzyne intermediate, the solvent-adduct (71) (K. Chow, N.V. Nguyen and H.W. Moore, J. Org. Chem., 1990, 5.5, 370). Analogous thermolysis of azidoquinones, as (72), results in symmetrical fragmentation to afford 2 mol of the corresponding cyanoketene (73) (H.W. Moore et a/., J. Org. Chem., 1990, 5.5, 3876). Electro-oxidative desorption of 2,2'-bisdehydrohydroquinone adsorbed at a benzenoid moiety on a platinum surface probably results in initial formation of the bis-quinone followed by oxidative cleavage of the adsorbed ring to afford the dicarboxylic acid (74); a more detailed understanding of electrochemical processes of this type may lead to the development of new synthetic methodology (A.T. Hubbard, Heterogeneous Chemistry Rev., 1994, 1, 3, and references therein).

28 CI

O

Me3S,~" ""3

O (69)

(70)

O

OH

,oC'X

R

R~~- x~ -N3

O II R~~CN

CN (71)

(72)

(73)

The oxidative cleavage of catechols to the corresponding (Z, Z)-muconic acids has long been considered to occur via the 1,2benzoquinones, and evidence of their transient involvement has been obtained from studies of the auto-oxidation of compounds such as 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxymandelic acid, and 3,4-dihydroxyphenylalanine (DOPA)in the presence of ~cyclodextrins in alkaline media (A.V. Eiiseev and A.K. Yatsimirskii,

CO2H

c~ "~,

__. OH

O O (74)

O2H CO2H . ~

(75)

"CHO (76)

29 J. Org. Chem., 1994, 5_99,264). However, cleavage of the 3,5-di-tbutylcatechol ring, to afford breakdown products such as (75) and (76), by oxygen in the presence of catalytic iron(ll) and water occurs via catechol-iron complexes; 3,5-di-t-butyl-l,4-benzoquinone is also formed, and survives (T. Funabiki et a/., J. Chem. Soc., Chem. Commun., 1994, 1453, 1951). Similar chemistry may be involved in the degradation of lignins (K. Valli et al., Appl. Environ. Microbiol., 1992, 5_88,221), and in the iron(Ill) catalysed oxidative degradation of 4-substituted-l,2-dimethoxybenzenes (veratroles): electronaccepting substituents such as formyl and acetyl induce the formation of muconic acids, whereas donor substituents such as tbutyl and hydroxymethyl lead to the formation of 5-substituted-2methoxy-l,4-benzoquinones (1. Artaud, K. Ben-Aziza and D. Mansuy, J. Org. Chem., 1993, 5._88,3373). Although 1,2- and 1,4-benzoquinones can be destroyed by oxidation, a route favoured in Nature involves reduction to the corresponding hydroquinones followed by oxygenation prior to ringcleavage (cf. D.L. IIIman, C&EN, 1993, 7.j.1,July 12, p.26).

1

(a)

Synthesis of Benzoquinones From Phenols and Hydroquinones and their Ethers

Treatment of 2,3,5-trisubstituted (variously H, Me, OMe) anisoles with dimethyl dioxirane affords the corresponding 1,4benzoquinones, sometimes quantitatively (W. Adam and M. Shimizu, Synthesis, 1994, 560). Oxidation of 2,5-dimethylphenol with hydrogen peroxide catalysed by a cerium(IV)-calix[8]arene gives a moderate yield of 2,5-dimethyl-1,4-benzoquinone, but similar treatment of phenol and 2,6-dimethylphenol results in hydroxylation only, the products being hydroquinone and its 2,6-dimethyl homologue respectively (H.M. Chawla, U. Hooda and V. Singh, J. Chem. Soc., Chem. Commun., 1994, 617). Calix[1-6]-para-quinones can be obtained by oxidative de-tbutylation of the corresponding 4-t-butylcalixarenes using thallium(Ill) trifluoroacetate (J.-D. van Loon et al., J. Org. Chem., 1990, 55, 5639; C.D. Gutsche et al., Isr. J. Chem., 1992, 32, 89; J.

30 Org. Chem., 1993, 5__88,3245; see also M. Tashiro et al., J. Org. Chem., 1990, 5,5, 2404). The calix[4]quinone is formed in good yield by oxidation of the corresponding hydroquinone with iron(Ill) chloride (Y. Morita et a/., J. Org. Chem., 1992, 5"7, 3658). Substituted 4-hydroxy-N,N-dimethylbenzylamines afford the corresponding 1,4-benzoquinones, including prenyl-1,4benzoquinones, when oxidised with Fremy's salt in a two-phase aqueous buffer - dichloromethane system (J.M.Sa& et a/., J. Org. Chem. 1992, 5.!, 589; 1993, 5_88,328). Hydroquinone monomethyl ether yields 1,4-benzoquinone when treated with aqueous nitric acid (B.D. Beake, J. Constantine and R.B. Moodie, J. Chem. Soc., Perkin Trans. 2, 1994, 335). Ammonium cerium(VI) nitrate continues to find use for the conversion of substituted hydroquinone monomethyl ethers into the corresponding 1,4-benzoquinones (T. Yoon, S.J. Danishefsky and S. de Gala, Angew. Chem. int. Ed. Engl., 1994, 3__33,853); the use of this reagent as a one-electron oxidant has been reviewed (G.A. Molander, Chem. Rev., 1992, 9._22,29). Treatment of hydroquinone with periodate-doped silica gel in dichloromethane affords 1,4-benzoquinone essentially quantitatively (M. Daumas et al., Synthesis, 1989, 64); ammonium cerium(VI) nitrate can also be used for the heterogeneous oxidation of hydroquinones to the corresponding benzoquinones (J. Morey and J.M. Sa&, Tetrahedron, 1993, 4_.99,105), as can silver(I) carbonate in benzene (J.S. Yadav, V. Upender and A.V. Rama Rao, J. Org. Chem., 1992, 5._7.7,3242). Gaseous nitrogen oxides (NOx) catalyse the auto-oxidation of hydroquinones suspended in dichloromethane to give 1,4-benzoquinones, in very high yield (E. Bosch, R. Rathore and J.K. Kochi, J. Org. Chem., 1994, 59, 2529; R. Rathore, E. Bosch and J.K. Kochi, J. Chem. Soc., Perkin Trans. 2, 1994, 1157). The traditional industrial route to hydroquinone from benzene, via mononitration, reduction to aniline, manganese(IV) oxidation to 1,4-benzoquinone and then reduction with iron(ll), generates environmentally unfriendly by-products, and alternative routes are being sought. One involves the bacterial conversion of D-glucose into quinic acid, from which hydroquinone, and 1,4benzoquinone, can be obtained by treatment with aqueous manganese(IV) oxide ( K.M. Draths, T.L. Ward and J.W. Frost,, J. Am. Chem. Soc., 1992, 114, 9725). Another is based on the wellestablished synthesis of phenol and acetone from cumene hydroperoxide. Thus alkylation of benzene with propene is allowed

3] to proceed to 1,4-bisisopropylbenzene, catalytic oxidation with oxygen then affords the o~,o~'-bishydroperoxide, and rearrangement cleavage of this under acidic conditions yields hydroquinone and 2 mol of acetone (J. Haggi n, C&EN, 1994, 7_22,April 18, p.22). One-electron oxidation, via pulse radiolysis, of hydroquinones and catechols in aqueous solution produces the semiquinones which disproportionate to form the corresponding quinones, thus enabling these quinones, particularly very unstable ortho-quinones, to be studied in aqueous media under conditions which may resemble those encountered in vivo (C.J. Cooksey eta/., Melanoma Res., 1992, 2,283; E.J. Land, J. Chem. Soc., Faraday Trans., 1993, 8_99,803). Representative of these transient compounds are 3,4-mandeloquinone (77) (M. Bouheroum, J.M. Bruce and E.J. Land, Biochim. Biophys. Acta, 1989, 998, 57) and Nacetyldehydrodopaquinone (78) (M. Sugumaran et a/., J. Biol. Chem., 1992, 267, 10355). -

O~o O

CO2H

H

(77)

O~,",,~ NHAc O (78)

Further evidence for the stabilisation of ortho-benzosemiquinones by complexation with zinc(ll) in aqueous solution has been provided by electron spin resonance spectroscopy (R.P. Ferrari et a/., Spectrochim. Acta, A, 1993, 4_.99,1261 ).

(b)

From Cyclobutene- 1,2-diones

Insertion of cobalt into 2,3-dimethylcyclobutenedione gives maleoylcobalt complexes such as (79) which on photolysis afford a transient diketene which can be effectively trapped with alkynes, R'C=-C.R2 to yield, following removal of the cobalt, the corresponding 1,4-benzoquinones (80) (L.S. Liebeskind et al., Organometallics, 1986, 5, 1086; J. Am. Chem. Soc., 1987, 109,

32 2759). In a further development, involving different ligands and Lewis acid (rather than photochemical) activation, the benzoquinone (81) has been prepared from 3-isopropyl-4methoxycyclobutene-l,2-dione (L.S. Liebeskind et al., Tetrahedron Lett., 1990, 31,3723). O

O

O

Cp /

-~ O (79)

CO

R2 O (80)

i

O (81)

The route developed by H.W. Moore and his collaborators is of particular importance because of its versatility, which enables it to be used for the regiospecific synthesis of not only a wide variety of substituted 1,4-benzoquinones per se, but also '1,4-benzoquinones' carrying fused heterocyclic systems (see, e.g., S.T. Perri, P. Rice and H.W. Moore, Org. Synth., 1990, 69,220). It is based on the addition of alkenyl- and alkynyl-lithiums to mono- and di-substituted cyclobutene-1,2-diones to yield the corresponding e~-ketols (82) and (83) in which R ] - R4 may be variously alkyl, aryl, heteroaryl, alkoxy, and trialkylsilyl. Thermolysis, under comparatively mild conditions, affords, respectively, transient ketenes (84) and (85) which cyclise to yield, probably, diradicals, such as (86) from the alkene (84), and (87) from the alkyne (85); hydrogen transfer, which may be intermolecular, then affords the hydroquinone (88), which can be oxidised conventionally to the corresponding quinone, and, in the case of (87), the quinone (89; R4 = H) directly (H.W. Moore, et al., J. Am. Chem. Soc., 1990, 112, 1897, 5372; J. Org. Chem., 1991, 56, 4048; 1992, 57, 3765, 6896; 1994, 59, 2276). Methyl ethers (82; OMe instead of OH) can also be used (L.S. Liebeskind, K.L. Granberg and J. Zhang, J. Org. Chem., 1992, 57, 4345).

33

R~..

R2

R3

II

R 1"

O

R3

I \ OH R4

R

(82)

(83)

R 2,,,,,,,,~e~'% R 3

R3

RI~R 4 OH

OH

(84)

(85)

O

O

@

R3

Rlf-~

o

OH

OH

(86)

(87)

, R3

O

OH

RI.."~

R4

R2

R3

R1

R4

OH

O

(88)

(89)

A recent variation, which extends the alkyne route to the direct synthesis of tetrasubstituted 1.4-benzoquinones. involves

34 thermolysis of the o~-ketol (83) in the presence of tributyltin(IV) methoxide, which affords the stannylquinones (89; R4 = SnBu3); palladium-induced coupling with aryl iodides, including substituted phenyl (methoxy, nitro and amino groups are tolerated) and various heterocyclic iodides, then yields the corresponding 1,4benzoquinones (89; R4 = aryl, heteroaryl) (L.S. Liebeskind and B.S. Foster, J. Am. Chem. Soc., 1990, ! 12, 8612; L.S. Liebeskind and S.W. Riesinger, J. Org. Chem., 1993, 58,408; see also J.P. Edwards, D.J. Krysan and L.S. Liebeskind, J. Org. Chem., 1993, 58, 3942). Moore's group has recently introduced the vinylcyclobutenone (90) as a new synthon for precursors of his thermolysis route to 1,4-benzoquinones; alternative substitution patterns can be generated via conjugate [1,6] Michael addition of nucleophiles to the dienone system (H. Liu et al., J. Org. Chem., 1994, 59, 3284).

\

OMe

I [i [ OMe (90)

Thermolysis of (83; R 1 = OMe, R2 =, e.g., CH2CH2S-9anthracenyl, R3 = CH2Ph), in which R 2 is a potential intercalator, in the presence of supercoiled DNA results in strand-cleavage, possibly via the diradical intermediate, as (87) (H.W. Moore et al., J. Org. Chem., 1994, 59, 2276). The use of substituted 2-alkoxy-4-vinyl-2-cyclobutenones allows catechols, which can be oxidised subsequently to yield the corresponding ortho-benzoquinones, to be prepared by an analogous sequence of reactions (A. Gurski and L.S. Liebeskind, J. Am. Chem. Soc., 1993, 115, 6101 ). Overall, the development of these versatile and synthetically useful methods represents a new era in the synthesis of quinones.

3.5 11

(a)

Benzoquinone Methides Overview of Quinone Methide Reactivity

The benzoquinone monomethides, of which the ortho (91) and para (92) isomers are the parents, occupy a unique position in that conjugate Michael addition of nucleophiles to the methylene groups of either, and cyclo-addition to the exocyclic enone system of the ortho-isomer, lead immediately to a benzenoid product, and are therefore thermodynamically favoured processes. In each case, Michael addition of the nucleophile affords a phenolate directly (two steps, addition and enolisation, are required to reach this level with a benzoquinone); the corresponding addition to a benzoquinone dimethide is less favourable since the immediate product is a benzylic carbanion. The properties of 1,2- and 1,4-benzoquinone dimethides have been reviewed (J.L. Charlton and M.M. Alauddin, Tetrahedron, 1987, 43, 2873). As with 1,2-benzoquinones, [4 + 2] cycloaddition to both 1,2benzoquinone mono- and di-methides occurs readily, in the dimethides with inverse electron demand (D.L. Boger and S.M. Weinreb, "Hetero Diels-Alder Methodology in Organic Synthesis", Academic Press, San Diego, 1987), because benzenoid systems [dihydrobenzopyrans and benzopyrans from the monomethides with alkenes and alkynes respectively (G.C. Paul and J.J. Gajewski, J. Org. Chem., 1993, 58, 5060), and the corresponding tetra- and dihydronaphthalenes from the dimethides (H. Fujihara, M. Yabe and N. Furukawa, J. Org. Chem., 1993, 58, 5291)] are formed directly.

CCo

~

H2

,(,) 0

(91)

(92)

36 This special reactivity towards nucleophiles is an important contributor to the mechanism of cancer chemotherapy via bioreductive alkylation with quinones (H.W. Moore and R. Czerniak, Med. Res. Rev., 1981, !, 249) exemplified particularly by the mitomycins (based on indole-4,7-quinones) and the anthracyclines (in which a 9,10-anthraquinone is central) where reduction to the semiquinone, or to the hydroquinone dianion or its equivalent, results in expulsion of a strategically placed leaving group with concomitant generation of a quinone methide; alkylation of DNA bases can ensue (see, e.g., M.G. Peter, Angew. Chem. Int. Ed. Engl., 1989, 28,555; G.E. Adams et al., eds, "Selective Activation of Drugs by Redox Processes", Plenum, New York, 1990; see also D.C. Thompson et al., Chem.-Biol. Interactions, 1992, 86, 129). Further, 1,4-benzoquinone monomethides are involved in the sclerotisation (tanning) of insect cuticle (M. Sugumaran et al., Arch. Insect Biochem. Physiol., 1990, 14, 93, 237; 1991, 16, 31; FEBS Lett., 1991,279, 145; J. Biol. Chem., 1992, 267, 10355), and in the biosynthesis of melanins (M. Sugumaran, H. Dali and V. Semensi, Bioorg. Chem., 1990, 18, 144) and eumelanins (M. Sugumaran and V. Semensi, J. Biol. Chem., 1991, 266, 6073). They also contribute to the formation of neolignans (S.R. Angle and K.D. Turnbull, J. Org. Chem., 1993, 58, 5360) and lignins (S.M. Shevchenko and A.G. Apushkinskii, Russ. Chem. Rev., 1992, 61,105; E. Tsuchida and K. Yamamoto, in J. Reedijk, ed., "Bioinorganic Catalysis", Dekker, New York, 1993, Chap. 4; H. Set&l& et al., J. Chem. Soc., Perkin Trans. 1, 1994, 1163).

(b)

1,2-Benzoquinone Methides

In solution, the epoxides (93) are in equilibrium with the corresponding dark red monomethides (94), which predominate when R = OMe rather than H; they are trapped by methanol to yield the phenols (95), and by ethyl vinyl ether to give the chromans (96) (W. Adam et al., Angew. Chem. Int. Ed. Engl., 1993, 32, 735; Synthesis, 1994, 111). Substituted 1,2-benzoquinone monomethides are also formed, conveniently, by thermolysis of benzoxaborins (97), and can be trapped in the presence of Lewis acid activators by a variety of nucleophiles including alcohols, enols (at carbon), amines, and thiols (C.K. Lau, et al., Can. J. Chem., 1989, 67, 1384; 1992, 70, 1717; see also S.H. Woo, Tetrahedron Lett., 1993, 34, 7587).

3"7 Thermolysis of 4H-1,2-benzoxazines has also been employed (M. Yato, T. Ohwada and K. Shudo, J. Am. Chem. Soc., 1990, 112, 5341); the parent compound is formed by gas-phase pyrolysis of chroman, and can be trapped stereospecifically by both (E)- and (Z)-2-butene (G.C. Paul and J.J. Gajewski, J. Org. Chem., 1993, 58,

506o). Ph

Ph

N

(94) O

(95) R2

R1 R

O B

Et (96)

OMe

R

R

(93)

Ph.

"Ph

(97)

Conjugate elimination of the elements of water from substituted saligenins (2-hydroxybenzyl alcohols) has often been used as a route to the corresponding 1,2-benzoquinone monomethides, and is involved in the formation of phenolformaldehyde resins, and, relatedly, of calixarenes (C.D. Gutsche, in J.L. Atwood, J.E.D. Davies and D.D. MacNicol, eds, "Inclusion Compounds", Oxford University Press, Oxford, 1991, Vol. 4, Chap. 2; I. Alam, S.K. Sharma and C.D. Gutsche, J. Org. Chem., 1994, 59, 3716), but the generality of the method has recently been enhanced by the use of better leaving groups at the benzylic position, e.g. as (98) in which X is thiolyl (T. Inoue, S. Inoue and S. Kato, Chem. Lett., 1990, 55; Bull. Chem. Soc. Japan, 1990, 63, 1647) or benzotriazolyl (A.R. Katritzky et al., J. Org. Chem., 1994,

38 5_99,1900); synthetically useful trapping at the methylene group, in situ, then ensues. a2

R1 ,

SiMe3 X

HO'~'~

O.~~

R2~~

R2

(98)

cH2 "O

R1

R1

(99)

(100)

Elimination can also be effected from 1,4-benzoquinones, as (99); the resulting methides (100) can be trapped with alcohols, carboxylic acids and enol ethers, the latter affording 2alkoxychromans (K. Karabelas and H.W. Moore, J. Am. Chem. Soc., 1990, 11.2, 5372). 1,2-Benzoquinone monomethides may be intermediates in the photoregeneration of alcohols which have been protected as I](o-hydroxystyryl) dimethylsilyi ethers (M.C. Pirring and Y.R. Lee, J. Org. Chem., 1993, 58, 6961), and in the formation of coumarins by gas-phase pyrolysis of o-hydroxycinnamates (M. Black et al., J. Chem. Soc., Chem. Commun., 1993, 959). 1,2-Benzoquinone dimethides have been extensively studied, particularly as transient reactants in syntheses, notably those based on [4 + 2] cycloadditions. The parent compound is conveniently prepared by thermolysis (at 80 oC) of 1,4-dihydro-2,3benzoxathiin 3-oxide, with extrusion of sulfur dioxide (M.D. Hoey and D.C. Dittmer, J. Org. Chem., 1991,56, 1947; see also G. Kanai, N. Miyaura and A. Suzuki, Chem. Lett., 1993, 845). It has also been obtained by an improved (potassium iodide - [18]crown-6) Finkelstein elimination from (~,o~'-dibromo-o-xylene, and trapped with buckminsterfullerene (C6o) (P. Belik et al., Angew. Chem. Int. Ed. Engl., 1993, 32, 78); various substituted 1,2-benzoquinone dimethides, prepared by the thermolysis of benzocyclobutenes, also form adducts with C60 (A. Gegel et al., Angew. Chem. Int. Ed.

39 Engl., 1994, 3,3,559; M. lyoda et al., J. Chem. Soc., Chem. Commun., 1994, 1929). (z-Substituted 1,2-benzoquinone dimethides can be generated by thermal extrusion of sulfur dioxide from cyclic sulfones (S.P. Maddaford and J.L. Charlton, J. Org. Chem., 1993, 5_88,4132), and by treatment of the corresponding 13-substituted o(tributylstannylmethyl)styrenes with arylsulfenyl chlorides (H. Sano, K. Kawata and M. Kosugi, SYNLETT, 1993, 831). Fluoride-induced elimination from benzylsilanes (101) may produce the ketenes (102) which can be scavenged with aldehydes to yield 3,4-dihydroisocoumarins, with fumarates to afford o~tetralones, and with 3,4-dihydroisoquinolinium salts to give 8oxoberbines; some of the products may arise directly from the benzylic carbanion without loss of X; the balance is controlled by the leaving-group power of X and the nucleophilicity of the medium (S.V. Kessar, eta/., J. Org. Chem., 1992, 57, 6716; cf. H. Fujchara, M. Yabe and N. Furukawa, J. Org. Chem., 1993, 5_.68,5291). Interestingly, the parent ketene (102; R = H) is formed By Xradiolysis of benzocyclobutenone in an argon matrix (T. Bally and J. Michalak, J. Photochem. Photobiol. A: Chem., 1992, 6_.99,185). Generation of an imino analogue of (102) has been described (A.R. Deshmukh et al., Synthesis, 1992, 1083). Treatment of the chromium carbonyl compound (103) with butyllithium at low temperature generates the alcoholate which fragments to the corresponding dimethide, which can be trapped by methyl acrylate; photochemical removal of chromium then affords cis-2-methoxycarbonyl-l-tetralol (E.P. KQndig, G. Bernardinelli and J. Leresche, J. Chem. Soc., Chem. Commun., 1991, 1713). R

O

~SiMe3

R

[~.~,OcH2

~~OAc Cr(CO)3

(101)

(102)

(103)

40 The most important route to 1,2-benzoquinone dimethides involves the thermolysis of benzocyclobutenes (vide supra, and, e.g., K. Kobayashi et al., J. Chem. Soc., Perkin Trans. 1, 1992, 3111; J.J. Fitzgerald, N.E. Drysdale and R.A. Olofson, Synth. Commun., 1992, 22, 1807; A.R. Deshmuhk et a/., J. Org. Chem., 1992, 5_!, 2485). It has been employed successfully in the construction of a wide range of fused-ring systems via intramolecular [4 + 2] cycloaddition, e.g. the formation of (104) from (105) in boiling o-dichlorobenzene, where R contains a chiral auxiliary which allows (104) to be taken on to complete the first enantioselective total synthesis of (+)-cortisone (K. Fukumoto et al., J. Org. Chem., 1990, 5.5, 5625); an extensive review of these and related reactions is available (T.-L. Ho, "Tandem Organic Reactions", Wiley-lnterscience, New York, 1992). The outcome of some of these cyclisations may be influenced by the presence or absence of oxygen (K. Kobayashi et al., J. Chem. Soc., Chem. Commun., 1992, 780).

R ..

~

H

H

H MeO

MeO (104)

(105)

An example of cyclisation on to a phenyl group is provided by the methylenecyclobutenol (106), which thermolyses in 50% yield to the 9,10-anthraquinone methide (107); a dehydrogenation, possibly effected by an intermediate or a by-product, is required in order to complete the process (J.-C. Bradley, T. Durst, and A.J. Williams, J. Org. Chem., 1992, 57, 6575); an example of rearomatisation of a dimethide by a [1,5] hydrogen shift has been described (G. Dyker, Angew., Chem. Int. Ed. Engl., 1994, 33, 103).

4]

OH

O ph

I Ph (106)

~ Ph (107)

Intramolecular abstraction of benzylic hydrogen by a photoexcited ortho carbonyl group has also provided a useful entry to 1,2benzoquinone dimethides, which have been trapped by alkenes to afford 1-hydroxytetralins (J.L. Charlton and M.M. Alauddin, J. Org. Chem., 1986, 51,3490; J.L. Charlton and K. Koh, J. Org. Chem., 1992, 57, 1514; R.M. Wilson and K.A. Schnapp, Chem. Rev., 1993, 93, 223) and, from (108), allowed to collapse to the benzocyclobutenol (109) as a single diastereoisomer (P.J. Wagner, D. Subrahmanyam and B.-S. Park, J. Am. Chem. Soc., 1991, 113 709).

O

(108)

OH

(109)

The quinone dimethide resulting from photo-induced extrusion of carbon monoxide from 1,1,3,3-tetramethylindanone has been used for the detection of nitric oxide, with which it gives a nitroxide having a characteristic electron spin resonance spectrum; it could be useful for the detection of nitric oxide in biological systems (H.-G. Korth et al., Angew. Chem. Int. Ed. Engl., 1992, 31,

42 891; see also I.M. Gabr, U.S. Rai and M.C.R. Symons, J. Chem. Soc., Chem. Commun., 1993, 1099). An unusual, quantitative, preparation of 1,2-benzoquinone dimethide is by photolysis, in a variety of solvents, of the bisselenoether (110): in situ scavenging with electron-poor alkenes and alkynes affords the corresponding [4 + 2] adducts in 84 - 97% yield (H. Fujihara, M. Yabe and N. Furukawa, J. Org. Chem., 1993, 58, 5291).

~

Se Se (110)

(111)

(112)

Benzo[b]thiete (111) represents a source of 1,2-benzothioquinone monomethide (K. Saul et al., Chem. Ber., 1993, 126, 775; Liebigs Ann. Chem., 1993, 313). The bisthiete (112) behaves analogously, stepwise, on photolysis or thermolysis; interestingly, scavenging with either maleate or fumarate results in trans addition (H. Meier and A. Mayer, Angew. Chem. Int. Ed. Engl., 1994, 33, 465).

(c)

1,4-Benzoquinone Methides

Monomethides can be obtained under mild conditions via oxidation of appropriately substituted catechols to the corresponding 1,2-benzoquinones: both (77), by decarboxylation (M. Bouheroum, J.M. Bruce and E.J. Land, Biochim. Biophys. Acta, 1989, 998, 57), and (78), by tautomerisation (M. Sugumaran et al., J. Biol. Chem., 1992, 267, 10355), afford the corresponding 1,4benzoquinone methides, that from the decarboxylation of (77) tautomerising to 3,4-dihydroxybenzaldehyde. Direct oxidation of 4-alkylphenols can also be used. Thus treatment of the phenol (113) with a large excess of silver(I) oxide in dichloromethane yields the comparatively stable methide (114),

43 which on treatment with zinc(ll) chloride cyclises to the methylenecyclopentane (115) in high yield (S.R. Angle and K.D. Turnbull, J. Am. Chem. Soc., 1989, 111, 1136): samarium(ll) iodide is also effective for this type of cyclisation (S.R. Angle and J.D. Rainier, J. Org. Chem., 1992, 57, 6883), although cyclisation on to methoxy-activated phenyl residues can occur 'spontaneously' in aqueous acetonitrile at pH 6.8 (U.T. Bhalerao, C.M. Krishna and G. Pandey, J. Chem. Soc., Chem. Commun., 1992, 1176; see also H. Set&l& et al., J. Chem. Soc., Perkin Trans. 1, 1994, 1163). Intermolecular [3 + 2] cycloaddition of styrenes has also been observed (S.R. Angle and D.O. Arnaiz, J. Org. Chem., 1992, 57, 5937). OH

.SiMe3 (113)

O

OH

--(, SiMe 3 (114)

CH2 (115)

Treatment of a mixture of 2,6-di-t-butyl-4-methylphenol and acetylacetone with manganese(Ill) acetate in acetic acid affords, in low yield via a radical-driven 13-elimination of the 4-methyl group, the methide (116) (H. Nishino et al., J. Org. Chem., 1992, 57, 3551); the parent monomethide is formed when 4-bromomethyl-2,6-di-tbutylphenol is treated with triethylamine (K. Omura, J. Org. Chem., 1992, 57, 306). o~,o~-Bistrifluoromethyl-l,4-benzoquinone monomethide has also been prepared (J.P. Richard et al., J. Am. Chem. Soc., 1990, 112, 9507, 9513).

44 O

O

O

Ph~

Ph

O

(116)

(117)

(118)

Cyclic voltammetry has been used to study the redox chemistry of the monomethides (117; R = Me, But ) and the dimethide (118) (M.F. Nielsen et al., J. Chem. Soc., Chem. Commun., 1994, 1395), and of bis-ketene systems (J.H.P. Utley, Y. Gao and R. Lines, J. Chem. Soc., Chem. Commun., 1993, 1540). The parent 1,4-benzoquinone dimethide has been prepared by pyrolysis of the corresponding para cyclophane" it forms oligomers with C60 in toluene at -78~ C (D.A. Loy and R.A. Assink, J. Am. Chem. Soc., 1992, 114, 3977). The structure of a highly strained multiply substituted bis-cyclobutene-fused benzoquinone dimethide has been established by X-ray crystallography (J.-D. van Loon, P. Seiler and F. Diederich, Angew. Chem. Int. Ed. Engl., 1993, 32, 1706). The chemistry of 7,7,8,8-tetracyano-1,4-benzoquinone dimethide (TCNQ) continues to attract attention. It forms cyclophanes by addition to spiro-cyclopropanes (T. Tsuji, T. Ishihara and S. Nishida, J. Org. Chem., 1993, 58, 1601), and suffers displacement of a cyano group and concomitant reductive aromatisation to a merocyanine-type zwitterion under prolonged treatment with triethylamine (M. Szablewski, J. Org. Chem., 1994, 59, 954). However, the major effort has been directed towards the synthesis of lipophilic derivatives and analogues [J. Miura eta/., J. Org. Chem., 1988, 5,3, 439; H.E. Katz and M.L. Schilling, J. Org. Chem., 1991,56, 5318; C.A. Panetta et al., SYNLETT, 1991, 301; S.L. Vorob'eva and N.N. Korotkova, J. Chem. Res. (S), 1993, 34; H. Isotalo et al., J. Chem. Soc., Chem. Commun., 1994, 573] for the

45 development of novel redox systems (K. Takahashi, Pure Appl. Chem., 1993, 6.5, 127; K. Takahashi and S. Tarutani, J. Chem. Soc., Chem. Commun., 1994, 519; S. Yoshida et al., J. Org. Chem., 1994, 5_99,3077), synthetic metals (T. Nakamura et a/., Synth. Met., 1993, 5__7,3853), and organic and organometallic molecular magnetic materials (J.S. Miller and A.J. Epstein, Angew. Chem. Int. Ed. Engl., 1994, 33, 385). Thiobenzoquinones

,

Few data are available for these often very reactive compounds. The sulfones (119; R = H) (S. Thea et al., J. Org. Chem., 1985, 50, 2158), and (119; R = CI) and (120) (L. Field and C. Lee, J. Org. Chem., 1990, 55, 2558), and the thianthrene systems (121) and (122) (S.-R. Shin and H.J. Shine, J. Org. Chem., 1992, 57, 2706) have been described. CI R

O

R

O~ CI

SO 2

SO

(120) (121) NH ~S

,~~~S

O_ Ph

| (122)

(123)

SO 2

(124)

46 Treatment of 4-methyl-2-(phenylthio)phenol sulfoxide with thionyl chloride affords the cation (123) which can be trapped by conjugate addition (arrow) of phenols to yield biaryls (M.E. Jung, C. Kim and L. von dem Bussche, J. Org. Chem., 1994, 59, 3248). The formation of 1,2-benzoquinone monomethides from benzo[b]thiete (111) and the bisthiete (112) has been noted in Section 5(b). The imine (124) has also been prepared (L. Field and C. Lee, J. Org. Chem., 1990, 55, 2558). ,

(a)

Benzoquinone Imines

1,2-Benzoquinone Imines

N-Aroylimines such as (125) are N-arylated on treatment with 2,6-disubstituted phenols in methanol (H.W. Heine et al., J. Org. Chem., 1990, 5.5, 4039); they behave as heterodienes in DielsAlder reactions with alkenes (G. Desimoni, G. Faita and P.P. Righetti, Tetrahedron, 1991,47, 5857), and irt additions to anthracenes (at the 9,10- positions) (H.W. Heine eta/., J. Org. Chem., 1989, 5_44,5926). In these instances the quinonoid moiety becomes benzenoid, providing the driving force (cf___,1,2. benzoquinone monomethides). O

OH

CI N.Ar

Ar

CI (125)

Ar H

(126)

(127)

Treatment of o-aminopheny113-styryl ketones (126) with trifluoroacetic acid gives 2-aryl-2,3-dihydro-4-quinolones in high yield, possibly via iminomethides (127) (C.M. Brennan et al., Can. J. Chem., 1990, 68, 1780; C.D. Johnson, Acc. Ch. Res., 1993, 26, 476).

4"7

(b)

1,4-Benzoquinone Imines

Condensation of hydroxy-1,4-benzoquinones with phenylhydrazines and primary amines occurs at the carbonyl group adjacent to the hydroxy function, and probably yields the corresponding quinone imines which in the former case tautomerise to the azobenzenes (F. Wang et a/., J. Org. Chem., 1994, 5_fi, 2409); a corresponding, but equilibrium, tautomerisation has been observed for 4-hydroxyazobenzenes in which the hydroxy group is encircled by a macrocycle attached at the two positions ortho to it (E. Chapoteau et al., J. Org. Chem., 1991,5_.66,2575). Selective electro-oxidation of N,N'-bis-4-methoxyphenyl-2,2,2trifluoroethanimidamide and related compounds in aqueous acetonitrile produces the corresponding quinone monoimines (K. Uneyama and M. Kobayashi, J. Org. Chem., 1994, 5_.99,3003). N-Chloro-1,4-benzoquinone monoimines undergo Nhydroxyarylation in the presence of phenolates, providing intermediates for the synthesis of substituted acridines (P.F. Corey, et al., Angew. Chem. Int. Ed. Engl., 1991,30, 1646). The mechanism of acidic hydrolysis of N-acetyi-1,4-benzoquinone monoimines has been studied (M. Novak and K.A. Martin, J. Org. Chem., 1991,5_66, 1585). Selective mono-oxidation of calix[6]arene with alkaline ferricyanide in the presence of 4-diethylamino-2-methylaniline produces a quinone imine which acts as a selective sensor for the uranyl ion (UO22+) (Y. Kubo et al., J. Chem. Soc., Chem. Commun., 1994, 1725). The spiro-dienone (128) opens to the quinone imine (129)in light, and can be regenerated thermally, suggesting that the system may be useful in molecular switching (J. Salbeck et al., Angew. Chem. Int. Ed. Engl., 1992, 3.~.1,1498). Acetaminophen (paracetamol; 4-acetamidophenol)is bioactivated by oxidation to N-acetyl-1,4-benzoquinone imine, which scavenges nucleophiles via Michael addition (R.B. Silverman, "Organic Chemistry of Drug Design and Drug Action", Academic Press, 1992, Chap. 7). Photolysis of the diazo-compounds (130; R = H, Me) affords the carbenes, which react with oxygen to give the corresponding 1,4-benzoquinone-O-oxides, which have lifetimes in excess of 20

48 ILLS(B.R. Arnold et al., J. Org. Chem., 1992, 5.!, 6469; see also G. Bucher and W. Sander, J. Org. Chem., 1992, 5"7, 1346).

NHMe

0

a N

O [1

-(,)i

R

N2 (128)

(129)

(130)

1,4-Benzoquinone N-benzoyl N-phenylsulfonyldi-imines react with enamines to afford 2,3-dihydro-5-phenylsulfonamido-indoles (D.L. Boger and H. Zarrinmayeh, J. Org. Chem., 1990, 5.5, 1379). N,N-Dicyano-1,4-benzoquinone di-imines have received attention as electron acceptors in organic and organometallic complexes which conduct electricity (A. Aum(~ller and S. H(~nig, Angew. Chem. Int. Ed. Engl., 1984, 2,3, 447; Liebigs Ann. Chem., 1986, 142; S. Henig, Pure Appl. Chem., 1990, 62,395; S.H(~nig et a/., Adv. Mater., 1991, 3, 225, 311; M.R. Bryce, Chem. Soc. Rev., 1991,20, 355; M.R. Bryce et al., J. Org. Chem., 1991,5_!7, 1690; S. HOnig et a/., Angew. Chem. Int. Ed. Engl., 1992, 3_!, 859). Poly(aniline) containing a 1"1 ratio of secondary amino and 1,4-benzoquinone di-imino residues becomes electrically conducting when the di-imino moiety is monoprotonated (R. Baum, C&EN, 1993, April 19, p. 36; see also J.C. Michaelson and A.J. McEvoy, J. Chem. Soc., Chem. Commun., 1994,79). ,

Homobenzoquinones

Homo-1,4-benzoquinones (131) are conveniently obtained by treatment of the 1,4-benzoquinone with a diaryldiazomethane (T. Oshima et al., Bull. Chem. Soc. Japan, 1988, 61,2507; 1989, 62, 2580; Tetrahedron Lett., 1993, 649; Chem. Lett., 1993, 1977). Some of these undergo thermal rearrangement, e.g., at 100 oC in

49 benzene, (131, R1 = R3 = Br; R2 = H; Ar = Ph) gives the xanthylium salt (132) (T: Oshima, K. Tamada and T. Nagai, J. Chem. Soc., Perkin Trans. 1, 1994, 3325). O RI,~,~Ar R2~ " ~ ~ 3

Ph He Ar

Br

(~

O (131)

O <J~~ ,~ gr ~

(132)

O (133)

The parent 'homo-1,4-benzynoquinone' (133) has a transient existence, but has been trapped with anthracene (T. Watabe, K. Oda and M. Oda, J. Org. Chem., 1988, 53, 216). Substituted 3,4-homo-1,2-benzoquinones isomerise to tropones when treated with boron(Ill) fluoride etherate (M.G. Banwell and M.P. Collis, J. Chem. Soc., Chem. Commun., 1991, 1343). ~

Benzoquinols (Hyd roxycyclohexadienones)

The most widely used methods of preparation involve the oxidation of ortho or para substituted phenols, particularly alkylphenols, but also 4-arylphenols, with phenyliodine bisacetate or trifluoroacetate (A. Varvoglis, "The Organic Chemistry of Polycoordinated Iodine", VCH, Weinheim, 1992; A. Pelter eta/., J. Chem. Soc., Perkin Trans. 1, 1992, 2246; 1993, 1891; P. Wipf eta/., J. Org. Chem., 1993, 5_68,1649, 7195; M. Kacun, D. Koyuncu and A. McKillop, J. Chem. Soc., Perkin Trans. 1, 1993, 1771; A. McKillop, L. McLaren and R.J.K. Taylor, J. Chem. Soc., Perkin Trans. 1, 1994, 2047), or by anodic oxidation (J.S. Swenton et al., J. Org. Chem., 1991,5_.66, 6156; 1992, 5_Z7,5568; 1993, 5__68,3308). The original Wessely oxidation [lead(IV) acetate in acetic acid] continues to be used (N.K. Bhamare, eta/., J. Chem. Soc., Chem. Commun., 1990, 739). Other oxidants include thallium(Ill) nitrate (T. Horie et al., J. Org. Chem., 1992, 57, 1038) and

50 chromium(VI) compounds [J. Muzart, J. Chem. Res.(S), 1990, 96]. Both sodium periodate (V. Singh and B. Thomas, J. Chem. Soc., Chem. Commun., 1992, 1211), and singlet oxygen, generated using Rose Bengal and visible light, have also proved effective (E. Navarro et al., Fitoterapia, 1992, 63, 251). Addition of alkyl- and aryl-lithiums to 1,4-benzoquinone affords the corresponding 1,4-benzoquinols (M. Solomon et al., J. Am. Chem. Soc., 1988, 110, 3702); perfluoroalkyl-lithium compounds behave similarly (H. Uno and H. Suzukib, SYNLETT, 1993, 91). Trifluoromethyltrimethylsilane, in the presence of potassium fluoride, behaves analogously, yielding the trimethylsilyl ether of the trifluoromethylbenzoquinol (G.P. Stahly and D.R. Bell, J. Org. Chem., 1989, 54, 2873).

(a)

1,4-Benzoquinols

Anodic oxidation of the hydroquinone diether (134) in the presence of methanol affords the bisketal (135) which can be hydrolysed selectively to the mono-protected 1,4-benzoquinone (136) (T.N. Biggs and J.S. Swenton, J. Org. Chem., 1992, 57, 5568). The corresponding dimethyl ketal reacts with Grignard reagents at the carbonyl group; cleavage of the resulting ketal with oxalic acid on silica gel affords the 1,4-benzoquinol (A. McKillop et a/., J. Chem. Soc., Chem. Commun., 1992, 1589). Aryl-lithiums behave analogously (J.S. Swenton et al., J. Org. Chem., 1993, 58, 3308). O~ O H

OMe

(134)

MeO

OMe

(135)

0

(136)

MeO

0

(137)

5] The resulting benzoquinols can be reductively aromatised to the corresponding 4-substituted phenols by treatment with sodium dithionite (K.A. Parker et al., J. Org. Chem., 1992, 51,5547) or zinccopper couple (J.S. Swenton et al., J. Org. Chem., 1993, 58, 3308). The corresponding ethers, such as 4-benzyl-4-methoxy-2,6dimethylcyclohexadienone, undergo quantitative dienone-phenol migration of the benzyl group when treated with aqueous acid, a rearrangement which is catalysed by certain antibodies (Y. Chen, J.-L. Reymond and R.A. Lerner, Angew. Chem. Int. Ed. Engl., 1994, 33, 1607). Treatment of 1,4-benzoquinone bisdimethylketal with titanium(IV) phenolates affords aryloxyhydroquinone dimethyl ethers in high yield (G. Sartori et al., J. Chem. Soc., Perkin Trans. 1, 1991, 3059). Oxidation of 4-methoxyphenol in the presence of sorbyl alcohol gives the transient benzoquinol ether (137), which undergoes spontaneous intramolecular Diels-Alder addition (A.E. Fleck, J.Ao Hobart and G.W. Morrow, Synth. Commun., 1992, 22, 179).

O

O

O

CO2Et

O

EtO2C (138)

CO2Et (139)

(140)

Several spiro-analogues and their ethylene ketals have been described (V.H. Pavlidis, H. Medcalf and I.G.C. Coutts, Synth. Commun., 1989, 19, 1247; J.S. Swenton, A. Callinan and S.J. Wang, J. Org. Chem., 1992, 57,78). Thermolysis of the spirocompound (138) at 145 oC results in cleavage of the cyclopropane

.52 ring to yield the enol ether (139); sensitised photolysis of (138) in the presence of penta-l,3-diene gives the o~-tetralone (140) (T.N. Biggs and J.S. Swenton, J. Org. Chem., 1992, 5__7_7,5568). Thermolysis of the cyclobutenones (141; R 1 = Bu or MeO; R2 = H or Me respectively) affords the corresponding spiro-oxiranes (142) (R.W. Sullivan et a/., J. Org. Chem., 1994, 5_99,2276). O RI~ Bn MeO

O.CH2R2

O Bn

MeO O

(141)

R2

(142)

O-O (143)

Peroxides, including the highly reactive spiro-dioxirane (143) (W.W. Sander, J. Org. Chem., 1988, 53, 2091), and the t-butyl peroxides (144, R 1 = H, OMe; R2 = AIk, Ar) [J. Muzart, J. Chem. Res.(S), 1990, 96] have also been described. O

OMe R1

~

I

Bu t~O (144)

(b)

O~CO2Et OAc (145)

(146)

1,2-Benzoquinols

The acetate (145), prepared by the lead(IV) acetate method, has been used as an intermediate in the synthesis of isotwistanes

53 (N.K. Bhamare et al., J. Chem. Soc., Chem. Commun., 1990, 739), and the transient spiro-oxirane (146), obtained by periodate oxidation of o-vanillyl alcohol, behaves as a diene towards [4 + 2] cycloaddition of spirocyclopentadienes (V. Singh and B. Thomas, J. Chem. Soc., Chem. Commun., 1992, 1211). Intramolecular mono- and bis-spirocyclisation of p_-tertbutylcalix[4]arene has been observed, the bis material being a mixture of three stereoisomers (A.M. Litwak et al., J. Org. Chem., 1993, 5_88,393).

(c)

1,4-Benzoquinol Imines

Electrolysis of 4'-alkyl- and 4'-aryl-acetanilides in methanolic lithium perchlorate - sodium hydrogen carbonate yields the imines (147) which can be hydrolysed to the corresponding ketones (J.S. Swenton et al., J. Org. Chem., 1993, 58, 867, 5607). Diazotisation of the aminoterephthalate (148) with nitrous acid followed by treatment with nickei(li) cyanide yields the protected, 'stable' (m.p. 152-153 oC), quinone diazide (149), the structure of which has been confirmed by X-ray crystallography (C.A. Panetta, Z. Fang and N.E. Heimer, J. Org. Chem., 1993, 58, 6146). O N.~R ~

O~ O H

O.

CO2Me

MeO

R2

(147)

MeO2C

O

MeO2C NH2 (148)

N(~

NQ

(149)

CO2Me

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Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds, Vol.III B, C,D(Partial), edited by M. Sainsbury 9 1995 Elsevier Science B.V. All rights reserved.

55

Chapter 9

DERIVATIVES OF BENZENOID HYDROCARBONS SUBST1TUENTS CONTAINING A SINGLE NITROGEN ATOM

WITH

S. M. Fortt

This chapter deals with material in much the same order as the 2nd edition, 1st supplement. The literature is covered from 1980 to 1993 inclusive. Other, more general reviews which contain much relevant information are: "Aromatics and Arenes" in "Methoden der Organischen Chemic" Eds. E. Mtiller and O. Bayer, Georg Thieme Verlag, Stuttgart, 1981, Vol 5/2b, "Comprehensive Organic Chemistry" Eds. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, Vol 4, p.423 and 'Whe Chemistry of the Functional Group: Supplement F, The Chemistry of Amino, Nitroso, Nitro Compounds and their Derivatives" Eds. S. Patai and Z. Rappoport, W'dey Interscience, Chichester, 1982. 1. Nitro Derivatives of Bcrlzene. it~ Homologues and other Substituted Benzenes (a) Prevaration Nitration General and Mechanistic Aspects A comprehensive treatise on the mechanism and kinetics of nitration has been published (K. Schofield, Aromatic Nitration, Cambridge University Press, Cambridge, 1980). Aspects of industrial nitration have also been discussed (K.L. Dunlap in Kirk-Othmer Encyclopaedia of Chemical Technology. Eds. M. Grayson, D. Eckroth, Wiley Interscience, Chichester, 3rd Edition, Vol. 15, p.916 and G. Booth in Ullman's Encyclopaedia of Industrial Chemistry, Eds. B. Elvers, S. Hawkins and G. Schulz, VCH, Weinheim, 5th Edition, 1991, Vol. A17, p a l l ) . The possible formation of radical cations as intemaexfiates in aromatic nitration is of current interest (J. H. Ridd and J. P. B. Sandall, J. Chem. Soc., Perkin Trans., 2, 1986, 327; R. B. Moodie et al., ibid., 1985, 467; 1986, 1097). The relevance of electron donor-acceptor (EDA) complexes is highlighted in a detailed study of electrophilic aromatic substitution (J. K. Kochi, Pure Appl. Chem., 1991, 63, 255). Interestingly, the nitration of arenes by oxidation of

56

their charge-transfer complexes with nitrosonium salts has been demonstrated. Products and isomer ratios are similar to those arising from ordinary clcctrophilicnitration(E. K. Kim and J. K. Kochi, J. Org. Chem., 1989, 54, 1692). The directing effect of the trifluoromethyl group in nitration has been studied under a variety of conditions (G. A. Olah et al., J. Am. Chem. Soc., 1987, 3708). Ipso-nitration continues to attract attention. Nitration of anilines with p-alkyl substituents occurs by ipso-attack followed by 1,3 rearrangement of the nitro group (J. H. Ridd et al., J. Chem. Sot., Perkin Trans. 2, 1981, 518). The mechanism, rate-profiles and isotope effects of this reaction have been thoroughly studied (J. H. Ridd et al., ibid., 1983, 331, 1185, 1191). 2Alkylphenols are similarly nitrated at low temperature in acetic anhydride to give initially cyclohexa-2,4-dienones that rearrange to o-nitrophenols (A. Fischer and G. N. Henderson, Tetrahedron Lea., 1980, 21,4661).

~

OH

HNO3Ac20 -4(PC

OH NO2

R

R

R

Nitration of 2,4,6-trimcthylphenolleads to a mixture of 4-nitzocyclohcxa-2,5dienone and 4-nitrocyclohexa-2,4-dienone, the latter rearranging to the former. This can be isolated, but is slowly converted into 2,6Mimcthyl-4nitrophenol (G. G. Cross et al.,Can. J. Chem., 1984, 62, 2803). 0

OH OH 0

NO2 NO 2

57 The direct observation (1H,13C N ~ ) of a monocyclic dienone, formed by addition of nitronium ion to an unsubstituted position of 2,6-di-t-butylphenol, has be~n reported. The relative stability of the dienone is attributed to steric effects. Thus nitration of 2,6-di-t-butylphenol leads to 2,6Mi-t-butyl-4nitrophenol and 2-t-butyl-4,6-dinitrophenol via intermexfiates 2,6Mi-t-butyl-4nitrocyclohexa-2,5-dienone and 2,6-di-t-butyl-4,6-dinitrocyclohexa-2,4dienone respectively (G.G. Cross, A. Fischer and G.N. Henderson, ibid., 1984, 62, 1446).

H

-2~

.

NO2

NO2

~ ~) ~-,2 NO2

NO2 NO2

Preparative Aspects Much recent work is characteriseA by the need for the regioselective mononitration of reactive arenes. Nitrobenzene is best prepared with a deficit of nitric acid-sulfuric acid (K. Gramatikov et al., Bioteknol. Khim., 1989, 1, 23). Toluene, when nitrated with nitric acid in the presence of m o n ~ o n i t e clay, shows little msubstitution and a 2:1 preference for the formation of the p-isomer over the oisomer (H. Suzuki, H. Koide and T. Ogawa, Bull. Chem. Soc. Jpn., 1988, 61, 501). Nitronium tetrafluoroborate complexed with crown ethers mononitrates benzene and toluene (B. Masci, J. Chem. Sot., Chem. Commun., 1982, 1262). The mononitration of phenols can be achieved by metal nitrates absorbeM onto silica gel (R. Tapia, G. Torres and J. A. Valderrana, Synth. Commun., 1986, 16, 681), or various clay supports (A. Cornelius and P. l.aszlo, Synthesis 1985, 909). Sodium nitrate-lanthanium (III) nitrate in a 2phase system is also effective for mononiwation of phenols (M. Ouertani, P. Gerard and H. B. Kagan, Tetrahedron Lett., 1982, 4315). Anilines are pnitrated by urea nitrate in sulfuric acid. Interestingly, if the p-position is

58 blocked m-substitution occurs selectively (T. P. Sura, M. M. V. Ramana and N. A. Kudav, Synth. Commun., 1988, 18, 2161). The transfer-nitration of arenes with N-nim>-pyridinium and N-nitro-quinolinium salts is reported (G. A. Olah et al., J. Am. Chem. Sot., 1980, 102, 3507). N-Nitropyrazole in the presence of Lewis acids provides a useful reagent for the mononitration of arenes (G. A. Olah, S. C. Narang and A. P. Fung, J. Org. Chem., 1981, 46, 3533). The use of silver nitrate in acetonitrile with boron trifluofide as catalyst allows the selective mononitration of a variety of polymethylbenzenes in good yield, although treatment of hexamethylbenzene with an excess of nitronium tetrafluoroborate provides a very clean dinitration leading to dinitroprehnitene (G. A. Olah et al., ibid., 1981, 46, 3533; Helv. Chem. Acta, 1990, 73, 1167). 4-Methyl-4-nitro-2,3,5,6-tetrabromocyclohexa-2,5-dienone mononitrates activated arenes (A.M. Kashmttri and A.M. Munawar, J. Mat. Sci. Math,, 1988, 28, 289) via a radical mechanism (J.H. Ridd, S. Trevellick and J.P.B. Sandall, J. Chem. Sot., Perkin Trans. 2, 1992, 1535). The preparation of polynitrobenzenes and polynitrotoluenes is of continuing interest. Three isomeric aminotetranitrotoluenes are prepared by mixed acid nitration of appropriate aminodinitrotoluenes and subsequent aromatic nitramine rearrangement. (R.L. Atldns, R.A. Hollins and W.S. Wilson, J. Org. Chem., 1986, 51,3261). Me

Me I-I2SO4

NI--I2

-,~ -NO2 NHNO2

Me H2SO4

O2N

NO2

NH2

The apparent ipso nitration of 4-amino-2,6-dinitrotolucnr to pentanitroanilinr under these conditions is described and oxidation, or ammonolysis, allows the synthesis of hexanitrobenzene and 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), respectively. Oxidation of these polynitroanilines is best achieved using ozone in oleum or hydrogen peroxide in oleum (R.L. Atldns et al., ibid., 1980, 45, 2341; 1984, 49, 503). The thermal rearrangement of the intermediate niwamine to diazo-phenols is also studied (R.L. Atkins and W.S. Wilson, ibid., 1986, 51, 2572). More recent work is described in which 2,3,4,5-tetranitrotoluene is prepared via deamination of the corresponding

59 tetranitrotoluidine by treatment with nitrosylsulfuric acid and hypophosphorus acid (A.T. Nielson et al., ibid., 1994, 59, 1714).

Me O2N~~]~ NO20NOSO3 H

Me O2N~'~ NO2

o2N

o2N-'T++ -No2

NH2

NO2

H2SO+

then

Me H3PO2 -O2N_O2N~L~ NO2.~ 'NO2

N2

A similar strategy has been used for the preparation of other polynitroarenes such as decanitrobiphenyl (A.T. Nielson et al., ibid., 1983, 48, 1056). The nitration of m-dinitrobenzene to 1,3,5-trinitrobenzene by metal nitrate salt in superacid solution is suggested to involve a protonitronium cation as the nitrating species (G.A. Olah et al., J. Am. Chem. Sot., 1992, 114, 5608). The side chain nitration of a variety of acylpentanitrobenzenes is shown to be o-selective and can be of some synthetic utility (T.Keumi et al., J. Org. Chem., 1989, 54, 4034; 1986, 51, 3439). The reaction mcxtes involved in side chain nitration are discussed (H. Suzuki et al., Chem. Lea., 1987, 891).

o

Me

HNO3 .

Me

Me

Ac20

~'Y

Me

NO2 Me

R = pentyl

(b) Oxidation of Aromatic Amines Aromatic amines arc oxidiscd to the corresponding nitro compounds by dimethyldioxirane under phase-transfer conditions in excellent yield (D.L. Zabrowski, A.E. Moormann and K.R. Beck, Jr, Tetrahedron Lett., 1988, 29, 4501; R.W. Murray, S.N. Rajadhyaksha and L. Mohan, J. Org. Chem., 1989, 54, 5783). Sodium perborate in acetic acid is an effective reagent for the oxidation of electron-deficient anilines (A. McKillop and J.A. Tarbin, Tetrahedron Lett., 1983, 24, 1505). Fluorine reacts with wet acetonitrile to produce an oxidising agent for the oxidation of aromatic amines to nitroarenes. The procedure has been applied to the preparation of an 180 containing nitro derivative (M. Kal and S. Rozen, J. Chem. Soc., Chem. Commun., 1991, 567).

60 (c) Properties and Reactions The syntheses, structures and properties of the g-complexes, Meisenheimer complexes and anion radicals formed by aromatic nitro compounds have been reviewed (A. Goraczko and K. Kozlowski, Pr. Wydz. Nauk. Tech., Bydgoskie Tow. Nauk., Ser. A, 1985, 15, 73). The formation of MeisenheingT complexes has been specifically and comprehensively reviewed (F. Terrier, Chem. Rev., 1982, 82, 77; E. Buncel in The Chemistry of the Functional Group, Supplement F, The Chemistry of Amino, Nitroso, Nitro Compounds and their Derivatives. Eds. S. Patai and Z. Rappoport, Wiley Interscience, Chichester, 1982, Chap.27, p.1225). A review on the history, structure and mechanism of formation of coloured Janovsky complexes is also available (J. Prousek, Chem. Listy, 1986, 80, 714). The aromatisation of anionic Janovsky a-complexes by Noxopiperidinium perchlorate allows the substitution of nitroarenes by acetone (A.K. Sheinkman, T.S. Chmilenko and G.G. Vdvokina, Zh. Org. Khim:, 1983, 19, 2218). The electron donor-accepter (EDA) complexes formed by tri- and dinitrobenzenes with hydroxyaromatic Schiff bases and N-substituted anilines have been studied (M. Gaber, G.B. Mohamed and M. Abd-el-Ghafa, J. Chem. Soc. Pak., 1987, 9, 423; N. Radha, D. Begum and J.S. Mary, Ind. J. Chem., See. A, 1987, 26A, 1006). The relative acidities of 4-nitro, 2,4-dinitro and 2,4,6-trinitrotoluene are considered ( J. Lelievre, P.G. Farrell and F. Terrier, J. Chem. Sot., Perkin Trans. 2, 1986, 333). The X-ray structure of cis-2-nitrostilbene shows that the molecule is in fact not planar and that there is no hydrogen bond between the nitro group and hydrogen atom on the central double bond (Z.V. Todres et al., Zh. Org. KhirrL, 1987, 23, 1805). The photochemical reduction of nitroarenes has been studied by timeresolved ESR spectroscopy in order to elucidate the initial processes involved (K. Akiyama et al., Bull. Chem. Soc. Jpn., 1986, 59, 3269). The first observation of chemically-induced dynamic electron-spin polarisation (CIDEP), due to nitrobenzene anion radicals in the presence of an electron donor, proves that radical generation takes place through a triplet mechanism. Photoreduction of nitroarenes with 10-methyl-9,10-dihydroacridine ( a NADH analogue) in the presence of perchloric acid leads to anilines (S. Fukuzumi and Y. Tokuda, Bull. Chem. Soc. Jpn. 1992, 65, 831), as does photo-reduction in the presence of semi-conductor particles (F. Mahdavi,

61 T.C. Bruton and Y. Li, J. Org. Chem., 1993, 58, 744). The use of nitroarenes containing groups such as 2-nitrobenzyl and 3-nitrophenyloxycarbonyl for the preparation of so-called "caged" compounds relies on their photolability. The subject has been reviewed (V.N.R. PiUai, Synthesis, 1980, 1). Nitroarenes can be used as radiosensitisers to hypoxic tumour cells and the effect of sterically demanding o-substituents on reduction potentials has been examined (M. Boyd et al., J. Chem. Sot., Perkin Trans. 2, 1994, 29). Nitroarenes (and nitrosoarenes) are commonly used as dyestuffs (R. Raue and J.F. Corbett in Ullman's Encyclopaedia of Industrial Chemistry, Eds. B. Elvers, S. Hawkins and G. Schulz, VCH, Weinheim, 5th F~tion, 1991, Vol. A17, p.383). The first Friedel-Crafts reaction of nitrobenzene has been reported (Y. Shen, H. Liu and Y. Chen, J. Org. Chem., 1990, 55, 3961): nitrobenzene is ethylated by ethanol-sulfuric acid. Nitroarenes can be ftmctionalise~ by the addition of Grignard reagents, followed by oxidation of the resultant aryl nitronate adducts back to nitroarenes (G. Bartoli, Ace. Chem. Res., 1984, 17, 109). - O.~rOMgX ~2

RMgBr ~

~R

KMnO,

~R

Hydrolysis of the intemm~tr nitronatr allows the preparation of nitroso compounds. Alternatively, reduction with LAH, or sodium borohydridr in the presence of Pd/C, leads to a l k y ~ e s (G. Bartoli et al., Tetrahextmn, 1987, 43, 4221). A variety of nitroarenes undergo nucleophific substitution. The subject is reviewed (C. Paradisi, Comprehensive Organic Chemistry, Eds. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, Vol 4, p.423). Halogenonitroarenes are most commonly employed. Sulfodechlorination of 2,4-dinitrochlorobenzene with potassium dithionite under phase-transfer conditions leads to a high yield of the corresponding benzenesulfonic acid (M. Gisler and H. Zollinger, Angew. Chem., 1981, 93, 184). Similarly, nucleophilic substitution of halogenonitroarenes by ammonia and simple amines is commonly reported to proceed under moderate pressure (T. lbata, Y. lsogami and J. Toyoda, Chem. Lett., 1987, 6, 1187; H. Kotsuki et al., Synthesis., 1990, 1147; T. Watanabe et al., ibid., 1980, 39; N.S. Nudelman, S.E. Socolovsky, Tetrahedron. Lett., 1980, 21, 3331; J.J. Kulagowski and

62 C.W. Rees, Synthesis, 1980, 215), although nitroaryl triflates are substituted in acetonitrile under reflux at ordinary pressures (H. Kotsuld et al., ibid., 1990, 1145). The difference in behavior of 1~ amines and 2 ~ amines of similar basicity when the substrate contains an o-nitro group has been further discussed (R.E. Akpojivi, T.A. Emokpae and J. Hirst, J. Chem. Soc., Perkin Trans. 2, 1994, 443). However, treatment of o-bromo or o-iodonitrobenzenes with stable enolate anions and cuprous iodide in hot DMF leads to symmetrical 2,2'-dinitrobiaryls and not the expected substitution products (S.V. Thiruvikraman and H. Suzuki, Bull. Chem. Soc. Jpn., 1985, 58, 1597). Nitro groups themselves are substituted if suitably activated by other substiments (J.H. Gorvin, J. Chem, Res. S ynop., 1992, 7, 226). Aromatic fluoro compounds can be prepared by nucleophilic exchange of nitro group by fluoride anion (F. Effenberger and W. S treicher, Chem. Ber., 1991, 124, 157) - yields are dramatically improved if the leaving nitrite ion is immediately trapped (M. Maggini et al., J. Org. Chem., 1991, 56, 6406). Alkoxides react with m-dinitrobenzene under basic, platinum catalyse~ conditions to give aryl ethers (M.D. Conner and M.E. Ford, Chem. Ind., 1992, 47, 359). The uncatalysed displacement of aromatic nitro group by phenoxides is considered to involve a radical mechanism (P.G. Sammes and D. Thefford, J. Chem. Soc., Chem. Commun., 1987, 1373). The so-called vicarious nucleophilic substitution (VNS) of hydrogen in nitroarenes by certain carbanions has been reviewed (M. Makosza and J. W'miarski, Acc. Chem. Res, 1987, 20, 282). The carbanion must generally contain a good leaving group and a carbanion stabilising group. Good pselectivity (relative to the nitro group) is often obtained (M. Makosza et al., J. Org. Chem., 1984, 49, 5273, 4562, 1494; Chem. Lett. 1984, 1623, 1619). Y ~.. H,-~.CRY

proton

+ X NO 2 N+

-o" "o-

R=H,SPh,Ph

_ , .+_

X = S P h , C I , S R ~'

o NO

No2

Y = S P h , SOzPh, S R ~

The mechanism of such substitutions is thought to involve an intermediate Meisenheimer complex, but other details are by no means clear. The subject

63 has been discussed (G.P. Stably, B.C. Statdy and J.R. Maloney, J. Org. Chem., 1988, 53, 690). One notable example is provided by the VNS of hydrogen, not halogen, in 2,4-dinitrofluorobenzcne (M. Makosza and J. Stalewski, Liebigs Ann. Chem., 1991, 6, 605). The method is of synthetic utility for the preparation of (chloromethyl)nitroarenes (M. Makosza and M. Bialecki, Synth. Lett., 1991, 3, 181). Direct hydroxylation of nitroarenes occurs by VNS of hydrogen using t-butylhydroperoxide anion (T. Brose et al., J. Prakt. Chem. / Chem. Zeitung, 1992, 334, 497). The VNS method is also used for the direct amination of nitroarenes (see later). The rearrangement of o-nitrobenzylidene malonate derivatives - prepared via a modified Knoevenagel reaction - in the presence of 2 ~ amine leads to 2amino-4-nitrobcnzoic acids (S. Kinastowski, S. W n u k and E. Kaczmarek, Synthesis, 1988, I 11). The rcductive carbonylation of nitroarcnes continues to attract intense interest.The individualreaction steps that arc believed to occur during metal camlyse~ carbonylation of nitroaromatics to isocyanatcs, carbamatcs, amines and ureas arc reviewed (S.H. Han, G.L. Gcoffroy, Polyhedron, 1988, 7, 2331). Ph_NH 2

CO -CO 2

Ph-N

I N

/\

M---M

Ph-N-M

Ph

Ph M

M _-

I

M

*

/ \N

CO

Ph-N=C=O

M--M

\I

M

Halides dramatic~y promote the formation and earbonylation of imido ligands at the metal centre. The proposed reaction steps for the ruthenium dodecaearbonyl catalyse~ water gas reduction of nitrobcnzenr to aniline have been individually observed (S. Bahaduri et al., J. Chem. Soe., Dalton Trans., 1984, 1765). An IR study has also been reported (J.D. Gargulak, W.L. Gladfeltcr and R.D. Hoffman, J. Mol. Catal., 1991, 68, L89; J. Am. Chem. Soc., 1991, 113, 1054). The use of palladium and ruthenium complexes as catalysts has been reviewed (T. Ikariya, Shokukai, 1989, 31, 271) as have those of rhodium (K. Nomura, M. Ishino and M. Hazana, Bull. Chem. Soc. Jpn, 1991, 64, 2624; J. Mol. Catal., 1991, 66, L1, L11, L19; 1992, 73, L1).

64 The area has been comprehensively discusse~ in a recent review (S. Cenini, M. Pizzotti and C. Crotti, Aspects Homog. Catal., 1988, 6, 97). Methods for reducing nitroarenes to the corresponding nitroso, hydroxylamino or amino compounds are discussed under those specific headings. 2. Nitroso Derivatives of Benzene and its Homoloeues

(a) Preparation

Nitrosation Aspects of aromatic nitrosation are discussed in more general reviews (Nitrosation, D.L.H. Williams, Cambridge University Press, Cambridge, 1987 and 1988; R.B. Moody, Org. React. Mech., 1986, 263; 1985, 265; 1984, 269). The kinetics and mechanism of nitrosation using HNO 2 in H2SO4 / CF3CO2H-H20 have been thoroughly examined (V.L. Lobachev, E.S. Rudakov and O.B. Savsunenko, Kinet. Katal., 1990, 31,795, 789). The gasphase nitrosation of benzene has also been studied using ab initio M.O. calculations (K. Raghavachari, W.D. Reents Jr. and R.C. Haddon, J. Comput. Chem., 1986, 265).

Preparative Aspects An electrosynthetic method for the preparation of nitrosobenzenes is reported (C. Lamoureux and C. Moiret, Bull. Soc. C']aim. Fr., 1988, 59). The method is based upon the reduction of nitroarene at a first porous electrode, followed by oxidation of the phenylhydroxylamine at a ~ n d . Pure, unpromoted trimanganese tetraoxide is reported to be a suitable catalyst for the selective reduction of nitrobenzene to nitrosobenzene (T.L.F. Fauvre, P.J. Seijsener and P.J. Kooyman, Catal. Lea., 1988, 1,457) Pyridinium chlorochromate oxidation of arylhydroxylamines leads to nitrosoarenes (W.W. Wood and J.A. Wilkin, Synth. Commun., 1992, 22, 1683). A new general method for the conversion of aromatic amines to the corresponding nitroso compounds has been described (E.C. Taylor et al., J. Org. Chem., 1982, 47, 552; 1984, 49, 2500) DMS, NCS

,~

9 NaOH

,nC

^

+

A

-N-SM OH

,

A

-N-O

65 (b) Prot)erties and Reactions The mutagenicity of certain p-substituted nitrosobenzenes has been related to their electron releasing ability (R.I. Gupta, M. Singh and T.R. Juneja, Ind. J. Exp. Biol., 1987, 25, 445). The substituent and solvent effects in the UV absorption spectra of nitrosoarenes have been detailed (G. Wan and M. Giurginca, Rev. Roum. Ofim., 1986, 31, 857). The EDA complexes of nitrosodimethyl~iline have been studied (J. Moskal, A. Moskal and P. Milart, Pol. Acad. Sci. Chem., 1984, 32, 317). The formation of mixed dimers in systems containing aliphatic and aromatic nitroso compounds have also been studied (V.A. Batyuk et al., Vesta. Mosk. Univ. Ser 2 Khim:, 1988, 29, 270). The use of nitroso compounds for the spin-trapping of inorganic radicals has been recently reviewed (D. Rehorek et al., Chem. Soc. Rev., 1991, 20, 341; Free Radical Res. Commun. 1990, 10, 75). The chemistry of aromatic nitroso compounds has been recently describext (Y.E. Belyaev, Khimiya, Leningradskoe Otcl, Leningrad, 1989). The reaction of nitrosoarenes with glyoxylic acid provides a new path for the preparation of N-arylhydroxamic acids (M.D. Corbett and B.R. Corbett, J. Org. Chem., 1980, 45, 2834; Experentia 1982, 38,1310). NO

0

No2

CHO

'

HO'N"CHO

0 ~

The Diels-Alder reactions of nitrosoarencs (and the similar, more commonly used nitrosocarbonylarcncs) are reviewed (S.M. Wcinreb and D.L. Bogcr, Hetcro-Dicls-Aldcr Methodology in Organic synthesis, Academic Press, N.Y. 1987, p71 ; S.M. Weinreb and P.R. Staib, Tetrahedron, 1982, 38, 3087). The reaction of nitrosoarencs with oxygenated dicnes is particularly efficient and can have some synthetic utility (E.C. Taylor, K. McDaniel and J.S. Skotnicki, J. Org. Chem.,1984, 49, 250(>, K.F. McClure and S.J. Danishefsky ibid., 1991, 56, 850). The cycloaddition of nitrosoarenes to benzothiete leads to two new heterocyclic ring systems (K. Saul et al., Chem. Ber., 1993, 126, 775). So called 'cascade reactions' involve addition of nitrosoarenes to dicnes followed by a series of rapid reactions and rearrangements of the unstable Diels-Alder adducts (A. Dcfoin et al., Helv. Chitin Acta, 1989, 72, 1199).

66 The product of the reaction of nitrosobenzene with pyran-2-thione arises from no less than six consecutive steps (A. Defoin et al., Helv. Cbirn~ Acta, 1985, 68, 1998). Nitrosoarenes with stericaHy demanding substituents are often used as radical traps leading to nitroxide radicals that do not react further. However nitrosobenzene itself traps the 2-diphenylmethylene-l,3-cyclopentadienyl diradical to give an unusually fused isoxazoline (W. Adam, S.E. Bottle and K. Peters, Tetrahedron Lett., 1991, 32, 4283). The reaction of nitrosoarenes with anilines in the presence of hypervalent iodine provides a useful method for the preparation of unsymmetrical azoxyarenes (R.M. Moriarty et al., Synth. Commun., 1990, 20, 2353). Treatment of nitrosoarenes with arylaminodimagnesium reagents also allows preparation of unsymn~tical azoarenes (M. Okubo, T. Takahashi and K. Koga, Bull. Chem. Soc. Jpn., 1983, 56, 302). Nitrosoarenes are reductively carbonylated (H. Alper and G. Vasapollo, Tetrahedron Lett., 1987, 28, 6411). 3. N-Arylhydroxylamin~s (a) Preparation Traditionally N-arylhydroxylamines are prepared by the electrolytic reduction of the corresponding nitroarenes. However, other methods for accomplishing this transformation, without concomitant formation of products of overreduction are available. Tin (II) complexes, prepared by treatment of tin (II) chloride with appropriate amounts of thiol and triethylamine, reduce aromatic nitro compounds to the corresponding hydroxylamines (M. Bartra et al., Tetrahedron, 1990, 46, 587). Sodium borohydride in ethanol catalysed by tellurium rapidly reduces p-substituted nitrobenzenes to the corresponding arylhydroxylamines (S. Uchida et al., Chem. Lett., 1986, 1069). Transferhydrogenation of a variety of substituted nitroarenes by hydrazine hydrate in ethanol-dichloromethane and Raney-nickel leads tO arylhydroxyamines, isolated as their benzohydroxamic acids (N.R. Ayyangar et al., Synthesis, 1984, 938). N-Arylhydroxylamines are also available from nitroarenes using o-xylene-cz,~-dithiol-iron complexes (K. Yanada, T. Nagano and M. Hirobe, Tetrahedron Lea., 1986, 27, 5113). The oxidation of secondary anilines by mCPBA in acetone affords o~, Ndiphenylnitrones which are reduced to the corresponding N-benzyl-Nphenylhydroxylamines by LAH in ether (J.W. Gorrod and N.J. Gooderhan, Arch. Pharm., 1986, 319, 261).

67 _ O.~w,,.ph HO.NAp FIN/ x Ph ~ mCPBA ~ IAH. ~ R

R

h

R

R=H,CI,Me Interestingly, N-allyl-N-arylhydroxylamines are available via the unusual 1,2addition of allyl Grignard reagents to nitroarenes, followed by LAH reduction in the presence of palladium on carbon (G. Bartoli et al., Tewahedron Lett., 1988, 29, 2251).

Ar --NO2

.

THF, -70aC

At'-

! ' OMga

OH

Co) Properties and Reactions Recent studies indicate that phenylhydroxylamine is intimately involved in aniline induced haemolytic anaemia (D.J. JoUow, S.J. Grossman and J.H. Harrison, Adv. Exp. Med. Biol., 1986, 197 (Biol. React. Intermed.3), 573). ESR studies show that the oxidation of phenylhydroxylamine by oxyHb to the phenylhydronitroxide radicalin turn leads to the thiyl radicals that arc causal in hacmolytic anaemia (K.R. Maples, P. Eycr and R.P. Mason, Mol. Pharmacol., 1990, 37, 311; T.P. Bradshaw et al., Adv. Exp. Med. Biol., 1991, 2831 (Biol.React. Intcrmcd. 4), 253). The 'selfoxidation reduction'of N-arylhydroxylamincs has received attention (C.H. Yang and Y.C. Lin, J. Chinese Chem. Soc., 1987, 34, 19). The prc-cquilibrium between phcnylhydroxylamincs and nitrosoarcnes has been further studied. It is shown that more electron-attractingp-substituents are obtained on the phcnylhydroxylaminc and more electron-releasing psubstitucnts are obtained on the nitrosobcnzcnc in accord with expcctcd maximisation of resonance stabilisation.(M.G. Hzzolatti and R.A. Yunes, Quire. Nova 1988, 11, 303). The subsequent condensation between these compounds in aqueous solution has been shown to be under general acid and base catalysis (A.R. Bccker and L.A. Stcmson, J. Org. Chem., 1980, 45, 1708).

68

NO

+

NHOH R2

RI

,

IdO_~H RI

o

1 R2

Rl and R2 interchange

RI

R2

mixture

The mechanism and kinetics of the Bambergcr-rcarrangemcnt have been studied in detail (T. Sone et al., J. Chem. Soc., Pcrkin Trans. 2, 1981, 29, 298; 1443). It is concluded that the reaction mechanism follows SN1 kinetics with the elimination of water from protonated phcnylhydroxylamine as the rate determining step. An intermediate nitrenium ion is then attacked intermolecularly by water. Treatment of N-arylhydroxylamines with acids in benzene leads to nitrenium ions that substitute the arcne. Thus in the presence of trifluoroacetic acid diphcnylamincs arc obtained and in the presence of the stronger acid, tfifluoromcthanesulfonic acid aminobiphcnyls are obtained (K. Shudo, T. Ohta and T. Okamato, J. Am. Chem. Soc., 198 l, 103, 645). Nitrenium ions are also generated by photolysis of aryl azides in benzene leading to diarylamincs (H. Takcuchi, K. Takano and K. Koyama, J. Chem. Soc., Chem. Commun., 1982, 1254). More recently the photolysis of some 1arylamino/alkylamino-2-mcthyl-4,Gdiphcnylpyridinium salts has been described, allowing the direct amination of benzene via nitrenium ions (H.Takcuchi et al., ibid., 1987, 961). The chemistry of arylnitrcncs has been specifically reviewed (E.F.V. Scrivcn et al., Angcw. Chem., 1979, 9 l, 965). Treatment of N-phcnylhydroxamic acids with vinyl acetate in the presence of Li2PdC14 affords 2,3-unsubstimted N-acylindolcs via a hetcro-Cope rearrangement of the N-phcnyl-O-vinylhydroxylaminc derivatives (P. Martin, Hclv. Chim. Acta, 1984, 67, 1647).

••'•S

OH ~"'OA'c ,cocH3

N-O , COCH3

",~ -NHCOCI_I3

, COCH3

The mechanism of nitrone formation by phenylhydroxylamine and furftwals under acid catalysis has bccn comprehensively studied (R. Fett, E.L. Simionatto and R.A. Yunes, J. Phys. Org. Chem., 1990, 3, 620).

69 Phenylhydroxylamine is employed in a variety of cycloaddition reactions which nomaally involve intermediate nitrones. For example, reaction with unsaturated aldehydes leads to isoxazolidinols and dioxazolidines (K.N. Zelenin et al., Khirrt Geterotsiki Soedin., 1987, 127ff, T. Sugimoto, M. Nojima and S. Kusakayashi, J. Org. Chem., 1990, 55, 4221). Reaction with allenic nitriles leads to quinolines (S.R. Landor et al., J. Chem. Sot., Perkin Trans 1, 1989, 251) 4. N-Arvlnitrones and N-Arvlnitroxides The preparation, properties and chemistry of N-arylnitrones and Narylnitroxides is discussed in more general reviews (H.G. Aurich in The Chemistry of the Functional Group Supplement F, The Chemistry of Amino, Nitroso, Nitro Compounds and their Derivatives. Ed S. Patai, Wiley Interscience, 1989, Chichester;, The Chemistry of Nitrones, Nitronates and Nitroxides, p.313-399 and Nitrones, Nitronates and Nitroxides, E. Breuer, H.G. Aurich and A. Nielson, Wiley lnterscience, 1989, Chichester). Reaction of pcntyl nitrite with an excess of aryl Grignard reagent leads to N,N-diarylhydroxylamines which are oxidised to diarylnitroxides (C. Bertie, Synthesis, 1983, 793). Similarly, N-nitrosodiphenylamine reacts with aryl Grignard reagents forming symmetrical diarylhydroxylamines which are oxidised by lead dioxide to diarylnitroxides (L. Cardellini, L. Greci and G. Tosi, Synth. Commun., 1992, 22, 201). A tetramethylene-bridged thiazolium salt catalyses the reaction of nitrobenzene with benzaldehyde and lriethylamine to give a, Ndiphenylnitrone (H. Inoue and S. Tamura, J. Chem. Sot., Chem. Commun., 1985, 279). A variety of r N-arylnitrones are prepared by the reactions of nitrosoarenes with the hydrolysis products of pyridinium salts formed by reaction of primary amines with 2-(ethoxycarbonyl)-4,6-diphenylpyrliums (A.R. Katritzky et al., Reel. J R. Neth. Chem. Sot., 1983, 102, 51). Ph

t. Hyd.

~/~co2m

9

2. ArNO

t. R

Ar = ~ N M e

2

70 cz-Aroyl-N-phenylnitrones are prepared by the silver oxide oxidation of the adducts of silyl enol ethers and nitrosobenzene (T. Sasuki, K. Mori and M. Ohno, Synthesis, 1985, 279). An interesting example of an acyl nitrone is provided by N-acetyl-l,4benzoquinonimine N-oxide. The nitrone undergoes rapid N-O rearrangement and is a strong acetylating agent (P.F. Alewood and I.C. Calder, Tetrahedron Lea., 1985, 26, 2467). A~-N-O

q5 0

N-OAt

q5 0

5. Aromatic Amines derived from Benzene arid its Homolo~es. Nuclear Primary Mono~mines (a) Prepara~ion Reduction of the Nitro Group Most papers published in this area describe protocols for the mild and selective reduction of nitro group in the presence of other reducible groups. Rapid reduction of nitroarenes is achieved with AI-NiCI2-THF (P. Sarmah and N.C. Barua, Tetrahedron Lett., 1990, 31, 4065) and Zn-NiCI2-MeOH (A. Nose and T. Kudo, Chem. Pharm. Bull., 1990, 38, 2097) - the latter system allowing reduction of nitro groups in the presence of car~nyl and carboxyl groups. Ni-A1 alloy, employed under basic conditions, is a useful reagent for the reduction of nitro, as well as nitroso, azoxy, azo and hydrazo compounds to aromatic amines (W. Oppolzer and P. Dudfield, Tetrahedron Lett., 1985, 26, 5037). A1 amalgam is also used (A.P. Krapcho and T.A. Collins, Synth. Commun., 1982, 12, 293) as are various metals in liquid ammonia (L. Maat, J.A. Peters and M.A. Prazeres, Reel. Tray. m . Pays-Bas, 1985, 104, 205). The use of iron powder in cone. hydrochloric acid continues (D.H. Klaubert et al., J. Med. Chem., 1981, 24, 742) and even A1 scrap has been used under these conditions (M.S. Khan et al., J. Chem. Soc. Pak., 1988, 10, 393; J. Mat. Sci. Math., 1990, 30, 63). The sensitivity of the Zinin reduction to the steric environment of the nitro group is further reported (T.E. Nickson, J. Org. Chem., 1986, 51, 3963). Sodium sulfide in aqueous 1,4-dioxan (Y. Lin and S.A. Lang, Jr., J. Heterocycl. Chem., 1980, 17, 1273) and under phase-transfer catalysis by _

71 tetrabutylammonium bromide (V.F. Shner et al., Zh. Org. Khim. SSSR, 1989, 25, 879) allows sele~ive reduction of nitro groups to amines. SnCI2 (F.D. Bellamy and K. Ou, Tetrahedron Lett., 1984, 25, 839), HgCl 2, MgC12, T~CI4 (J. George and S. Chandrasekaran, Synth. Commun., 1983, 13, 495) and SmI2 (Y. Zhang and R. Lin, ibid., 1987, 17, 329) all reduce nitroarenes to amines under mild conditions. Electrocatalytic reductions of nitroarenes using Devarda-copper electrodes in basic media are reportedly milder and more selective than those with conventional electrodes (G. Belot, S. Desjardins and J. Lessard, Tetrahe~on Lett., 1984, 25, 5347). Aromatic nitro groups are selectively reduced by thiols in the presence of iron or iron complexes (S. Murata, M. Miura and M. Nomura, Chem. Lett., 1988, 361; M. Kijima et al., J. Org. Chem., 1984, 49, 1434). Lithium cobalt (I) phthalocyanine is also used for the selective reduction of nitroarenes (H. Eckert, Angew. Chem. Int. Ed. Eng., 1981, 20, 208). Borane in THF is used for the reduction of nitro groups to amines (R.S. Varma and G.W. Kabalka, Synth. Commun., 1985, 15, 843), as has lithium aluminium hydride (A. Handan and J.W.F. Wasley ibid., 1985, 15, 71) and sodium borohydride (F. Rolla, J. Org. Chem., 1982, 47, 4327). A wide range of transition metal chlorides have been used in conjunction with sodium borohydride: TiCI4 (S. Kano et al., Synthesis, 1980, 695), SnCl2 (T. Satoh et al., Chem. Pharm. Bull., 1981, 29, 1443) FeCI2 (A. Ono, H. Sasaki and F. Yaginuma, Chem. Ind., 1983, 480), NiCI2 (J.O. Osby and B. Ganem, Tetrahedron Lett., 1985, 26, 6413; see also A. Nose and T. Kudo, Chem. Pharm. Bull., 1986, 34, 3905), CuCI (A. Ono, M. Hiroi and K. Shinazaki, Chem. Ind., 1984, 75). Sodium telluride (H. Suzuki, H. Manaki and M. Inouye, Chem. Lett., 1985, 1671) and benzenetellurol (N. Ohira et al., ibid., 1984, 853) are also efficient reagents for reduction of nitroaromatics to amines. Heterogeneous metal-catalysed hydrogenation of nitroarenes (see for example M.A. Avery, M.S. Verlander and M. Goodman, J. Org. Chem., 1980, 45, 2750) appears less widely used than the homogeneous metal-catalyse~ equivalent. The nature of the platinum catalyst and solvent effects in the hydrogenation of some chloronitrobenzenes have been discussed (J. Strutz and E. Hopf, Chem.-Ing.-Tech., 1988, 60, 297). A wide range of transition metal complexes have been used based principally on rutheniurn (F. Wada, M. Shimuta and T. Matsuda, Bull. Chem. Soc. Jpn., 1989, 62, 2709; Y. Watanabe et al., ibid., 1984, 57, 2440) palladium (P.K.

72 Santra and C.R. Saha, Chem. Ind., 1984, 713; S. Bhaltacharya and P. Khandual, Chem. Ind., 1982, 600) and platinum (Y. Watanabe et al., Tetrahedron Lett., 1983, 24, 4121) for the homogeneous metal catalyse~ reduction of a variety of nitroarenes. The use of such catalysts, immobilised on solid supports can lead to unusual selectivities (K. Mukkanti, S.Y.V. Rao and B.M. Choudray, ibid., 1989, 30, 251). Catalytic transfer-hydrogenation has been further studied. The transfer of hydrogen using triethylammonium formate or eyclohexene with Pd/C catalyst, (M.O. Terpko and R.F. Heck, J. Org. Chem., 1980, 45, 4926, 4992; S. Ram and R.E. Ehrenkaufer, Tetrahedron Lett., 1984, 25, 3415; R.A. Ranpulla and R.K. Russell, Synth. Commun., 1986, 16, 1229), hydrazine and Raney-nickel, (F. Yuste, M. Saldafia and F. Walls, Tetrahedron Lett., 1982, 23, 147; N.R. Ayyanger et al., Bull. Chem. Soc. Jpn., 1983, 56, 3159) and secondary alcohols and rhodium catalysts (K.F. Lion and C.H. Ching, J. Org. Chem., 1982, 47, 3018) allows selective reduction of nitroarenes to aromatic amines. Primary arylamines are also prepared by hydrogenolysis of aryl azides by catalytic transfer-hydrogenation using ammonium formate and Pd/C catalyst (T. Garteser, C. Selve and J.J. Delpeuch, Tetrahedron Lett, 1983, 24, 1609), or by (Ph3P)2CuBH4 reduction (S.J. Clarke, G.W.J. Fleet and E.M. Irving, J. Chem. Res. (S), 1981, 17). Sodium borohydride supported on ion-exchange resin has also been used (G.W. Kabalka, P.P. Wadganonkar and N. Chatla, Synth. Commun., 1990, 20, 293). Nuclear Amination

Aqueous NH 3 in formamide is reported to give high yields of anilines from activated halogenoarenes (H.J. Niclas et al., Z. Chem., 1985, 25, 137). The ammonolysis of simple aryl halides is reportedly improved using quaternary ammonium salts as phase-transfer catalysts (G. Barak and Y. Sasson, J. Chem. Sot., Chem. Commun., 1987, 1267). Phenols are converted to ~ilines by heating NH 3 and NH4C1 in a bomb at 180~ (A.M. Becker, R.W. Richards and R.F.C. Brown, Tetrahedron, 1983, 39, 4189). Electrophilic amination of aryUithiums and aryl Grignards is popular. A number of organic azides function as NH2+ synthons by metal hydride reduction of the lithiotriazene, or triazene, adducts formed. These include tosyl azide (J.N. Reed and V. Snieckus, Tetrahedron Lett., 1983, 24, 3795; N.S. Narasinhan and R. Ammanmanchi, ibid., 1983, 24, 4733), phenylthiornethylazide (B.M. Trost and W.H. Pearson, ibid., 1983, 24, 269), vinyl azides (E.W. Colvin, G.W. Kirby and A.C. Wilson, ibid., 1982, 3835)

73 and diphenylphosphorazidate (S. Mori, T. Aoyana and T. Shiori, Chem. Pharm. Bull., 1986, 34, 1524). O O

"

Ar-MgBr

N3--P(OPh)2 ,,- A r - N = N - N- - P (IIO P h ) 2

LAH

._ Ar_NH 2 .

Tetraphenylcyclopentadienone oxime-O-tosylate (R.A. Hagopian et al., J. Am. Chem. Sot., 1984, 106, 5753) and acetone oxirne-O-mesitylate (E. Erdik and M. Ay, Synth. React. Inorg. Metal-Org. Chem., 1989, 19, 663) also serve as NH2+ synthons by reactionwith aryl Grignards and reduction of the imines formed. O-(Diphenylphosphinyl)hydroxylamine also directly aminates aryl Grignard reagents (M. Bernheim and W. Schrott, Tetrahedron Lea., 1982, 5399). Anilines can also be prepared by the direct amination of arenes using trimethylsilyl azide (G.A. Olah and T.D. Ernst, J. Org. Chem., 1989, 54, 1203), or hydrazoic acid in the presence of both CF3SO3H and CF3CO2H (T. Takeuchi, T. Adachi and H. Nishiguchi, J. Chem. Sot., Chem. Commun., 1991, 1524). Vicarious nucleophilic substitution of nitroarenes leading to anilines has been described using 4-amino-1,2,4-triazole (A.R. Katritzky and K.S. Laevenzo, J. Org. Chem., 1986, 51, 5039) and sulfenamides (M. Makosza and M. Bealecki, ibid., 1992, 57, 4784) in the presence of strong bases. N-N

-

Nil ,IR

H2N-N ~ ~

B

NH 2

N

NI-~Cl

tBuOK, DMSO

_O.N-O -

NO2

_O,N,O_

Miscellaneous

Primary arylamines are prepared by the direct Ixrane-dimethylsulfide reduction of arylamides (H.C. Brown, S. Narasinhan and Y.M. Choi, Synthesis, 1981, 996, 605, 441). Reaction of aroyl chlorides with hydroxylamine-O-sulfonic acid in toluene at reflux leads to 1~ arylamines in a reaction similar to the Neber rearrangement (R.G. Wallace, J.M. Barker and M.L. Wood, ibid., 1990, 1143).

74

O

O

Ar.~Cl NH2OSO3H Ar.,JI,.N.O..sOzOH acidcaL

Ar-N=C=O

~

Ar--NI~

H

Treatment of 1~ N-arylamides with iodobcnzcne and formic acid in aq. acetonitrile also leads to 1~ arylamines as their formate salts (A.S. Radhakrishna et al., ibid., 1983, 538). Other well-known re.arrangements involving formation of isocyanates arc discussed later. Anilines can be prepared by Semmlcr-Wolff aromatisation of cyclohexenone oximes (Y. Tamura et al., ibid., 1980, 483, 887). The mechanism of this transformation has be~n studied (M.M. Yousif, S. Sacki and M. Hamana, J. Hetcrocycl. Chem., 1980, 17, 1029). The synthesis of 2-aminobcnzophenones has been reviewed (D.A. Walsh, Synthesis, 1980, 677). (b) Prooerties and Reactions 13C NMR data on m/p-substituted anilines is described in tcnns of substiment effects.(M. Budescnsky et al., Collect. Czech. Chem. Commun., 1991, 56, 368) and is also reported for aromatic amine-boranr adducts (M.A. Paz-Sandoval, Spe~trocim. Acta, Part A, 1987, 43A, 1331). The properties, manufacture and reactions of aniline (Y.T. Nikolacv and A.M. Yakukson, Khimiya, Moscow, 1984; S.A. Kudchadker, American Petroleum Institute Publication 718, Washington 1982) and o-anisidine (M.N. Morathe, Chem. Eng. World, 1987, 22, 36) have been reviewed. Anilines may be protected as their stabasr adducts by cyclocondcnsation with Me,2SiCICH2CH2SiMc2CI in the presence of tdcthylaminr (T. Hocgberg, Acta Phamm. Suec., 1986, 23, 414). Deprotr is achieved under mildly acidic conditions. Oxidation The oxidative dimerisation of aniline to ~nzidinr has been the subject of a molecular nmchanics study (D. I.ananbr et al., J. Chem. Soc., Perkin Trans. 2, 1991, 1437). The chemistry of the bcnzoquinonr in~e.s continues to attract attention. The kinetics and mechanism of the oxidative coupling reactions involving N,Nbis(2-hydroxyethyl)-p-phenylenextiaminr is describe~ (D.J. Palling, K.C. Brown and J.F Corbctt, J. Chem. Soc., Perkin Trans. 1, 1986, 65; 1981, 886). Benzoquinonr imines, not bcnzoquinonr N-chloramines, are the

75 reacting species involved in the Gibbs phenol assay (I. Pallagi and P. Dvortsak, J. Chem. Sot., Perkin Trans. 2, 1986, 105). The oxidation of arylamines to the corresponding nitroarenes has been previously mentioned (vide supra). Interestingly, a reexamination of samples of mauveine made by Perkin has shown that the literature structure is incorrect (O. Meth-Cohn and M. Smith, J. Chem. Sot., Perkin Trans. 1, 1994, 5). The Boyland-Sims (persulfate) oxidation of anilines gives not only o-sulfates, but also, contrary to previous work, substantial amounts of p-sulfates. The intermediates of the reaction are the arylhydroxylamine-O-sulfonates (E.J. Behrman, J. Org. Chem., 1992, 57, 2266; J. Chem. Sot., Perkin Trans. 1, 1992, 305). Halogenation Although electrophilic halogenation of anilines is well known, reliable and mild methods for selective monohalogenation are scarce. Regioselective monobromination of anilines has been reported using Nbromosuccinimide in DMF (F. Xu and Q. Wang, Huaxue Shiji 1986, 8, 374), bromine a b s o ~ onto zeolite (M. Onaka and Y. lzumi, Chem. Lett., 1984, 2007) and tetrabutylammonium tribromide (J. Berthelot et al., Synth. Commun., 1986, 16, 1641; Can. J. Chem., 1989, 67, 2061). A simple highly selective monobromination of anilines is afforded by treatment of the derived arylaminosilanes with N-bromosuccinimide in CO 4 and subsequent desilylation (W. Ando and H. Tsunaki, Synthesis, 1982, 263).

6 Br

Br

Treatment of anilines with 5,5-dibromo-2,2-dimethyl-l,3-dioxane-4,6-dione in DCM leads to p-bromoanilines in high yields (X. Huang and G. Wu, Huaxue Shiji, 1991, 13, 1). Deamination via Dediazotisation Dediazonisation by Sn/HCI in PEG-DCM gives good yields of arenes free from chlorinated products (N. Suzuki et al., Chem. Ind., 1985, 698). The synthetic applications of arenediazonium compounds are reviewed (Y. Hashida and S. Sekiguchi, Yuki Gosei Kogaku Kyokaishi, 1982, 40, 752) and their radical reactions discussed (C. Galli, Chem. Rev., 1988, 88, 765).

76 Fluorodiazotisation is perhaps the most common means of introducing fluorine into aromatic rings. The subject is reviewed (N. Yoneda and T. Fukuhara, Yuki Gosei Kagaku Kyokaishi, 1989, 47, 619). Nitrosonium tetrafluoroborate is a good reagent for accomplishing this transformation directly (D. Milner, Synth. Commun., 1992, 22, 73). Decomposition of the triazene formed by trapping diazonium ions with pyrrolidine in the presence of potassium iodide in CF3CO2H leads to aryliodides (N.I. Foster et al., Synthesis, 1980, 572). 3-Aryl-l-tetrazol-5-yltfiazenes have been used as a bench stable source of diazonium ion. The dediazoniation process is induced by acetic acid and does not involve free radicals (R.N. Buffer, P.D. O'Shea and D.P. Shelly, J. Chem. Sot., Perkin Trans. 1, 1987, 1039). Aromatic amines containing nitro substituents are deaminated by t-butyl nitrite in chloroform. Use of deuteriochloroform allows the preparation of deuterionitrobenzenes (K. Kikukawa and T. Koyama, Kinki Daigaku Kyushi Kogakubu Kenkyu Hokoku, Rigogaku-hen, 1989, 18, 1). Aryliminodimagnesiums The aryliminodimagnesiums derived from primary arylamine and ethyl magnesium bromide are especially useful for the preparation of antis by reaction with diaryl ketones (M. Okubu, S. Hayashi and M. Matsunaga, Bull. Chem. Soc. Jpn, 1981, 54, 2337) and for the preparation of unsymn~trical azo and azoxyarenes by reaction with nitroso and nitroarenes respectively (M. Okubu, K. Matsuo and A. Yamauchi, ibid., 1989, 62, 915; M. Okubu and IC Koga, ibid., 1983, 56, 203). The mechanistic aspects of these transformations are under study (M. Okubu et al., ibid., 1989, 62, 1621; 1991, 64, 196). N-Alkylation The N-alkylation of 1o arylamines is discussed more comprehensively below. 1o Arylamines add to terminal acetylenes in the presence of HgC12 as catalyst to give imines ( 2 ~ arylamines give enamines, J. Barluenga, F. Aznar and R. Liz, J. Chem. Sot., Perkin Trans., 1, 1980, 2732) and react regiospecifically with allylic alcohols in monoallylations catalysed by mercury (II) tetrafiouroborate (J. Barluenga, J. Perezprieto and G. Ascensio, Tetrahedron, 1990, 46, 2453). 6. Benzenediamines and Benzr (a) PreparatiQrl Phenyleneamines are most commonly prepared via the reduction of the corresponding nitroanilines (see, for example, E.A. Karakhanov et al., Neftekhimiya 1991, 31, 312; K. Nomura, M. Ishino and M. Hazama, Bull.

77 Chem. Soc. Jpn., 1991, 64, 2624; T.A. Parchevskaya, L.V. Bogutskaya and M.V. Belousov, Ukr. Khim. Zh., 1990, 56, 1268). o-Phenylenediamine is manufactured in a two step procedure involving nitration of aniline in acetic anhydride with 65% HNO 3 followed by reduction of the o-nitroanilide so obtained (CA, 1991, 115, P231846). o/p-Phenyleneamines are also manufactured from the corresponding dihalogenobenzenes by ammonolysis at elevated temperature, pressure in the presence of zinc or copper bromides and hydrocarbons (eg. n-nonane). Methods for the preparation of pphenylenediamine have been reviewed (M. Ignatowicz, Przem. Chem., 1984, 63, 520). o-Phenylenediamines are available via the rearrangement of aryl ketones in polyphosphoric acid (T. Benincori et al., J. Chem. Sot., Perkin Trans. 1, 1988, 10, 2721). Ph2CffiN-NHPh

acid cat -Ph2CO

~

NH2

Nil2

Catalytic reduction of phloroglucinol trioxime by Raney-nickel provides a convenient preparation of 1,3,5-triaminobenzene (I. Arai, Y. Sei and I. Murmatsu, J. Org. Chem., 1981, 46, 4597). NOH

.NH2 Ra-Ni, BuOAc

HON

NOH

H2N

NII2

(b) Propertie~ and Reactions N :5 Chemical shifts of 1,2-diaminobenzenes are reported (M. Sibi, Mag. Reson. Chem., 1991, 29, 400) and their energetics considered (D.A. Dixon A.C.S. SyrrL Ser. 1989, 404, 147). The charge-transfer spectra of the EDA complex of m-phenylenediamines with tetracyanoethylene have been compiled (B. Uno et al., Spectrochim. Acta, Part A, 1987, 43A, 995). Phenyleneamines find use in the preparation of synthetic fibres and dyes, as cross-linking agents as inhibitors in radical polymerisation and as antioxidants. Like some other aromatic amines they are mutagenic. Phenylenediamines are important for the preparation of drugs and pesticides (CA, 1989, 111, P57253z) and are monomers for the preparation of polyamides. The thermodynamics of polymerisation of phenylenediamines

78 with iso or terepthalic acids have been studied (N.V. Koryakin and I.B. Rabinovich, Vysokomol. Soextin. Ser. A, 1987, 29, 675). o/m-Phenylenediamines undergo a wide variety of cyclocondensations and are useful for the preparation of heterocycles, o-Phenylenediamine reacts with aminoacids to give benzimidazole derivatives with anti-bacterial activity (T.M. Aminabhavi et al., Inorg. C'him. Acta, 1986, 125, 125; O. Cherkaoui E.M.Essassi and R. Zniker, Bull. Soc. m . Fr. 1991, 225). Reaction with bis(dithiocarbamates) leads to bisCt~nzimidazoles) (J. Gavin et al., J. Heterocycl. Chem., 1990, 27, 221). o-Phenylenediamine is used to derivatise malto-oligosaccharides to quinoxalines in a HPLC method for the measurement of the degree of polymefisation (M. Takagi, Y. Daido, N. Morita, Anal. Sci., 1986, 2, 281) and commonly acts as a bidentate ligand in transition metal complexes ( see, for example, A. Prasad, L. Mishra and V.C. Agarwala, J. Chem. Sect.A: Inorg. Bio-inorg. Phy. The,or. Anal. Chem., 1991, 30A(2), 162). 7. N-Substitutexi Arvlamines (a) Preparatign

N-Alkylation A review of the methods for the mono and dialkylationof amines has been punished (H. Wurziger, Kontaktr 1987, 3, 8). Methods for the monoalkylation, of a~ilines most commonly involve the formation of intermediate arylimines (Schiff bases) or equivalents and subsequent convertion to alkylarylamine.Treatment with formaldehyde in the presence of sodium borohydridr (A.G. Giumanini et al.,Synthesis, 1980, 743; A.R. Katdtzky and A. Akutagawa, Org. Prep. Procedure Int., 1989, 21,340; S. Bhattacharyya, A. Chaterj~ and S.K. Duttachowdhury, J. Chem. Soc., Perkin Trans. I, 1994, I), or with ketones and diboranr in T H F (H.R. Morales and P-J Martin, Synth. Commun., 1984, 14, 1213) allows, monomethylation, or monoalkylation, of I~ arylamines l'r Monomethylation of anilines can also be achieved by treatment of N(alkoxymethyl)-N-arylamines, with sodium borohydddr in ethanol at reflux (J. Barluenga, A.M. Bayon and G. Ascensio, J. Chem. Soc., Chem. Commtm., 1984, 1334; L.E. Overman and R.M. Burk, Tetrahexiron Left. 1984, 25, 1635). Alternativelytreatment with mcthyllithium at -60~ leads to monomeric methyleneaxylamines which react on w a m ~ g with alkyllithiums to afford an overallmonoalkylation of I~ aromatic amines (J.Barluenga et al., J. Chem. Soc., Chem. Commun. 1983, I I09).

79

NHMo HN~OR

NaBH4 N=CH2 9 /

6

R

MeLi

~ R ~i~,,, HNAR

Thus N-(methoxymethyl)-N-phenylamine is used as a synthetic equivalent to N-methylenephenylamine (J. Barluenga et al., J. Chem. Sot., Perkin Trans. 1, 1988, 1631). lsolable monomeric N-methylenearylamines generally rely on steric hindrance by substituents at the o-position to prevent oligomerisation (F.P. Cortolano et al., Tetrahedron Lett., 1988, 29, 5875; A.G. Giumanini, G. Verardo and M. Poiana, J. Prakt. Chem., 1988, 330, 161). Similarly, N-(benzotriazolylmethyl)arylamines function as Schiff base equivalents and treatment with Grignard reagents leads to substitution of the benzotriazolyl moiety and the overall N-monoalkylation of 1~ arylamines (A.R. Katritzky, S. Rachwal and B. Rachwal, J. Chem. Sot., Perkin Trans., 1, 1987, 805). The method has been extended to the preparation of unsymmetrical N,N-dialkyanilines (A.R. Katritzky S. Rachwal and J. Wu, Can. J. Chem., 1990, 68, 456).

1. RIMgBr 2. R2MgBr

/"'R2 R~''NAr

Various N,N-diarylbenzylamines can be synthesised by reactions of N(arylmethylene)arenamines with (arylmethoxy)arenes in DMF in the presence of a strong base as a catalyst, which is obtained by reacting sodium metal with this solvent (M. Paventi and A.S. Hay, J. Org. Chem., 1991, 56, 5875). PhN= /

Ph

Na DMF '

ph~O v Ph

.

Ph Ph- N"

{" Ph

80 2 ~ and 3 ~ Arylamines are also available by treatment of thioamides with triethyloxonium tetrafluoroborate, followed by reductions with uxtium borohydride (S. Raucher and P. Klein, Tetrahedron Lett., 1980, 21, 4061). Similarly, 3 ~ amides are reduced to the corresponding amines by reduction of thioimidates with sodium cyanoborohydride (R.J. Sundberg, C. P. Walters and J.D. Bloom, J. Org. Chem., 1981, 46, 3730). Diborane reduction of amides in the presence of boron trifluoride also leads to 2 ~ and 3 ~ arylamines (H.C. Brown, S. N a r a s ~ and Y.M. Choi, Synthesis, 1981, 996, 605,

441). The formylation of anilines with acetic formic anhydride, followed by boranedimethylsulfide reduction, affords monomethylated anilines (S. Krishnamurphy, Tetrahedron Lett., 1982, 23, 3315).

CHO /~

AcOCHO

BH3SMe2

_20~C

Tt~

Trimethyl orthoformate in the presence of tosic acid monoalkylates 2 ~ arylamines (R.A. Swaringen, J.F. Eaddy and T.R. Henderson, J. Org. Chem., 1980, 45, 3986) and anilines are menoalkylate~ by alcohols in the presence of zeolites (M. Onaka et al., J. Chem. Soc., Chem. Commun., 1985, 1202 ; Chem. Lett., 1982, 11, 1783). Formamidines, based on N-methylaniline, can be deprotonated at the exposition and the resulting carbanions alkylate~ to give homologous amines (A.I. Meyers and S. Hellring, Tetrahedron Lett., 1981, 22, 5119).

~N.Me t.. N

t

1.BuLi 2.E 3.hyd.

ON~E H

Similarly, dimethylsulfoxide methylates anions derived from N-fonnylate~ ~ilir~es under phase-umlsfer conditions leading to monomethylated anilines, after aqueous work-up (V.K. Sharma, Ind. J. Chem. Se~t.B., 1983, 22B, 1153).

81 Unsymmetrical diarylamines have been prepared using methodology based on 1-aryl-2-ethoxycarbonyl-4,Gdiphenylpyridinium salts (A.R. Katritzky and A.J. Cozens, J. Chem. Sot., Perkin Trans. 1, 1983, 2611). Ph

Ph

NaH Ar migration Ar

At"

NHAr I

Ph hydrolysis "

HN/Arl ~Ar

Ar- N',Ar I

Arene Substitution Unsymmetrical diarylamines are synthesise~ by the coupling of arenes with nitrenium ions derived from aryl azides in the presence of triflic acid (H. Takeuchi and K. Takano, J. Chem. Sot., Chem. Commun., 1983, 447). Exchange reactions for the preparation of 2 ~ and 3 ~ anilines have been previously discussed. Palladium catalysed reaction of aryl bromides with N,Ndiethylamino(tributyl)tin leads to the corresponding diethylanilines (M. Kosugi, M. Kameyama and T. Migita, Chem. Lea., 1983, 927).

N-Dealkylation N,N-Dialkylanilines can be N-dealkylated selectively by photo-induced single electron-transfer in methanol (G. Pandey, K.S. Rani and U.T. Bhalerao, Tetrahedron Lea., 1990, 31, 1199).

Ring Synthesis The Diels-Alder reaction of vinylketenimines with acetylene esters leads to anthranilate esters (E. Differding and O. Vandevelde, ibid., 1987, 28, 397).

R TIPS

N~

NH2

TIPS

2Me

+ R~ ~

CO2Me

R

R

82 A one-step synthesis of 2,6-disubstimted 3~ anilines from aliphatic compounds is reported (P. Camps, C. Jaime and J. Molas, ibid., 1981, 22, 2487). The cycloaromatisation reactions of various enamines leads to 3~ arylamines (T.H. Chan and GJ. Kang, ibid., 1983, 24, 3051).

TMSCO2Me

~

Me~ ,

Me

Me" " ~ "OH

Miscellaneous

Alkyldiphenylsulfonium percklorates (B. Badet, M. Julia and M. RamirezMunoz, Synthesis, 1980, 926) and alkylsulfates also alkylate arylamines (I. Pop et al., Rev. Roum. Chim., 1988, 33, 283). N-Phenylation of anilines using triphenylbismuth acetate, or phenyllead triacetate in the presence of copper catalyst is reported (D.H.R. Barton et al., Tetrahedron Lett., 1987, 28, 3111 ; 1986, 27, 3615). 2-Oxazolidinones behave as aziridine equivalents for the aminoethylation of 1~ arylamines (G.S. Poindexter and D.A. Owens, J. Org. Chem., 1992, 57, 6257). N-Ethynylarylamines are available by flash pyrolysis of isoxazolones at 650~ (I-I. W. Winter and C. Wentrup, Angew. Chem., 1980, 92, 743), M e ~

N.O,,,~0

NHPh

FVP

HNPh =

tautomerises

~

HNPh~ m m

Reductive alkylation of nitro groups by methanol in the presence of ruthenium-phosphine catalysts gives N,N-dimethylanilines in high yields (K.T. Huh et al., Chem. Lett., 1988, 449). Treatment of nitroarenes with ethyl cyanoacetate and potassium hydroxide followed by hydrolysis leads to the corresponding amino derivatives in which an o-substituent is incorporated (Y. Tomioka, K. Ohkubu and M. Yamazaki, Chem. Pharm. Bull. 1985, 33, 1360).

83 (b) Properties and Reactions Oxidation

3 ~ Aromatic amines (when p substituted) form stable radical cations on oneelectron oxidation. The rate constants for the deprotonation of pAn2NCH3AsF6 (An = anisyl) by quinuclidine have been describe~ in a detailed kinetic study (J.P. Dinnocenzo and T.E. Banach, J. Am. Chem. Soc., 1989, 111, 8646; see also S.F. Nelson and J.T.lppoliti, ibid., 1986, 108, 4879). Nuclear Functionalisation

Methods for the regioselective nuclear alkylation, or alkenylation, of arylamines are reviewed (W.F. Burgoyne, Chemtech, 1989, 19, 690). In general acid catalysed alkene-alkylation of arylamines leads to good yields of o-alkylated compounds and allows the introduction of branched alkyl groups into this position (W.F. Burgoyne and D.D. Dixon, Appl. Cat., 1990, 63, 17). N-Alkylarylamines undergo exclusive o-acylation by alkyl nitriles in the presence of boron trichloride to give 2-acyl-N-alkylarylamines (K. Sasakura, Y. Terui and T. Sugasawa, Chem. Pharm. Bull., 1985, 33, 1836). N-(t-BDMS)-N-methylarylamine, when activated as its rl6-chromium tricarbonyl complex is substituted almost exclusively at the m-position by treatment with base and electrophile. This is attributed to the bulkiness of the silyl group. (M. Fukui, T. Ikeda and J. Oishi, ibid., 1983, 31,466). Me" N.TBDMS

/~e, N Me 1. BuLi, 2. PhCHO tL

Cr(CO)3

2.deproteet

Ph

OH A synthetic equivalent to o-lithio-N-methylaniline is described (H. Tanaka et al., Tetrahedron Lett., 1988, 29, 3811).

Me'N'OPr

Me'N'OPr

NHMc -Ni

84 The amino-Claisen reanmlgement has been further studied, but appears to give quite complex mixtures of products (I.B. Abdrakhmanov et al., Zh. Org. Khim., 1984, 20, 620; 1982, 18, 1466). The Fischer-Hepp rearrangement of some N-nitrosodiphenylamines has also been surveyed (S.P. Tetoria, A.K. Arinich and M.V. Gorelik, ibid., 1986, 22, 1562). The Meisenheimer reanangement of a series of N-(2- or 4-nitrophenyl) tertiary amine oxides has been the subject of a NMR and a kinetic study (AH. Kuthier et al., Org. Mag. Res. 1982, 18, 104; J. Org. Chem., 1981, 46, 3634). The mechanism is best descdbe~ as an intramolecular cyclic process and not as a homolytic dissociation-recombination sequence. 8. N-Arvlamides (a) Preparation The Beckmann rearrangement of oximes to anilides (often exploited for the preparation of anilines) has been reported to be promoted by aluminium iodide (D. Konwar, R.C. Boruah and J.S. Sandhu, Tetrahedron Lett., 1990, 31, 1063), or acidic clay (H.M. Meshrau, Synth. Commun., 1990, 3253). Ketoxime trirnethylsilyl ethers rearrange under the influence of antimony (V) salts (T. Mukuiyama and T. Harada, Chem. Lett., 1991, 9, 1653). Omius rearrangement of aroylazides under phase-transfer conditions leads to anilides (J.R. Pfister and W.E. Wymann, Synthesis, 1983, 38). Anilides can also be obtained via the diazotisation-rearrangement of tosylhydrazones of o/m-substituted benzophenones and a-substituted acetophenones (V. Joshi and R.K. Sharma, J. Ind. Chem. Sot., 1988, 65,

564). Formanilide is prepared via the formylation of aniline by pentafluorophenyl formate (L. Kisfaludy and L. Otvos Jr.,Synthesis, 1987, 5 I0), enol formates in the presence of ruthenium (H) (M. Neveux, C. Bruneau and P.H. Dixreuf, J. Chem. Soc., Perkin Trans. I, 1991, I197), and by N-formylformamide (prepared by ozonolysis of oxazole) (C. Kashima et al.,Tetrahedron Lett., 1989, 30, 156 I). Formanilide can also be prepared by reaction of aryl azides with the enolate of acetaldehyde (often formed by cycloreversion of T H F by BuLi) via the intermediate hydrotriazoles (L. Di Nunno and A. Scilimata Tetrahedron, 1986, 42, 3913) and by the sequential reductive N-formylation of nitroarenes in the presence of ruthenium (E.M. Nahmed and G. Jenner, Tetrahedron Lett., 1991, 32, 4917).

85

N3

6

OHC

+ H2C~L-S BuLl

THF

[~

~-c.o

proton

C~

~-~176

(b) Properties and Reactions The F ~ rotomerism of the amidc bond in formanflidc has been studied by dielectric polarisation showing considerable amounts of the Z isomer (K. Pralat and J. Jadzyn, Fiz. Dielektr. Radiospcktrosk., 1986, 13, 89). Fatty-acid anilides are suspected of causing toxic oil syndrome (A. Martinez Conde Ibanez, An. Quim. Ser.C, 1987, 83, 107; B. Kaphalia and G.A.S. Ansari, J. Anal. Toxicol. 1991, 15, 90). Diaminobenzan~des are useful for the preparation of certain polyng~ (polyamidines, CA, 1989, 110, P115509e). The telomerisation of anilides with butadiene in the presence of palladium catalyst is described (R.M. Safuanova, R.N. Fakhretdinov and U.M. Dzhemilev, Izv. Akad. Nauk. SSR. Ser. Khim. 1988, 821). The ruthenium catalyse~ N-alkylation of anilides with alcohols is also reported (Y. Watanabe, T. Ohm and Y. Tsuji, Bull. Chem. Soc. Jpn., 1983, 56, 2647). The photo-bromination of anilides by hexabromobenzene has been the subject of a mechanistic and kinetic study (M.M. Aly, I.M.A. Awad and A.M. Fahmy, Bull. Pol. Accad. Sci. Chem. 1987, 35, 77; Rev. Roum. Chim. 1983, 33, 167). Cyclocondensation of formanilides with benzofuroxane leads to unusual 2aryl-2H-benzotriazole-l-oxides (H.J. Niclas and B. G6hrmann, Synth. Commun., 1989, 19, 2141). N-Acylureas are prepared by the reaction of formanilides with phenylisocyanate (H.G. Schweim, Arch. Phann., 1987, 320, 430). N-Chloroanilides oxidise 1~ arylamines to the corresponding trans-azo compounds. A mechanism for this process has been proposed (A. Kumar and G. Bhattacharjee, J. Ind. Chem. Soc., 1991, 68, 523).

86

Nuclear functionalisation Acetaminophen (paracetamol) is manufactured from acetanilide by genetically engineered microbial synthesis (CA, 1987, 107, P5737h). The directed o-metalation reactions of N-arylamides have been recently reviewed (V. Snieckus, Chem. Rev., 1990, 90, 879; V. Snieckus and P. Beak, Acc. Chem. Res., 1982,15,3069. N-(t-Butyloxycarbonyl)aniline via the corresponding dilithio species gives a wide range of o-substituted anilines ( J.M. Muchowski and M.C. Venuti, J. Org. Chem.,1980, 45 4798; W. Fuhrer and H.Z. Gschwind, ibid., 1979, 44, 1133; S. Marburg and R.L. Tolman, J. Heterocycl. Chem., 1980, 17, 1333). H

tBu

uN'~oOtBu 2BuLi ~ N y O H EO

'Bu

{~~N.. ]{.-O hyd.

~ E NH2

The mechanism of the acid-catalyse~ Orton rearrangement in aprotic solvents has been studied for some N-bromo-4-chloroacetanilides. (P.D. Golding et al., Can. J. Chem., 1981, 59, 839). The mechanism is determined to be intramolecular, involving protonation of the substrate, followed by heterolytic fission of the N-Hal bond and intramolecular rearrangement of the resulting ion-pair to a g-complex. The Fries rearrangement of benzanilide in the presence of ZrOC12 (also TiC14, ThC14) gives good yields of p-aminobenzophenone (S. Ravi et al., Ind. J. Chem., Sect B, 1991, 30B, 443). The photo-Fries rearrangement in the presence of cyclodex~ leads to high o-selectivity (M.S. Syamala, N.B. Rao and V. Ramamurthy, Tetrahexiron, 1988, 44, 7234; M. Nassetta, R.H. De Rossi and J.J. Cosa, Can. J. Chem., 1988, 66, 2794). The translocation of the radical derived from o-iodoanilides by 1,5 H-atom transfer so as to give a radical adjacent to the anilide carbonyl is describe~ (D.P. ~ , A.C. Abraham and H. Liu, J. Org. Chem., 1991, 56, 4335).

87 9. N-Arvlisocvanates (a) Preparation Thermolysis of disilylated hydroxamic acids (prepared by reaction of hydroxamic acids with hexamethyldisilazide) gives isocyanates (J. Rigaudy and E. Lytwyn, Tetrahedron Lea., 1980, 21, 3367). TMSO. Ph~ = = N - O T M S

thermolysis -9

Ph- N=C=O

Arylisocyanates are synthcsised by the trifluomacetalisation of N,Ndiarylureas and subsequent thcrmolysis ( M.V. Vork and L.I. Samarai Ukr. Khim. Zh., 1990, 56, 1313), or by reaction of aryl carlxxiiimidcs with carboxylic acids (D.B. Guldcncr and D.J. Sikhema, Chem. Ind., 1980, 15, 628). Transition metal carbonylation of phcnylazidcs leads to phcnylisocyanatcs (G. La Monica and S. Cenini, J. Organomct. Chem., 1981, 216, C35) as does the reaction of carbon dioxide with aryliminophosphorancs (P. Molinai, M. Alajarin and M. Arques, Synthesis, 1982, 596). Adducts of nitrosocarbonylarenes and dimethoxyanthracene are decompose~ at 80~ in the presence of triphenylphosphine to give arylisocyanates in high yield. (J.E.T. Corrie, G.W. Kirby and R.P. Sharma, J. Chem. Sot., Perkin Trans. 1, 1982, 1371). (b) Prooerties and ReaCtions Quantum mechanical calculations on the conformation of phenylisocyanate suggest C-5 symmetry (M. Rernko et al., Z. Phys. Chem. 1987, 268, 874). A reinvestigation of the dipole moments of a series of p-substituted phenylisocyanates suggests a value of 7.93 x 10 -30 (ha-: as the dipole moment of the isocyanate group. (I. Daniel, F.Barnibol and P. Kristian, Collect. Czech. Commun., 1989, 54, 1441). A MINDO study is also reported (idem, Chem. Pap. 1989, 43, 609). Associative interactions of phenylisocyanate with nitrobenzene in hexadecane have been studied (M.G. Ivanov et al., Zh. Obshch. Khim., 1990, 60, 1209) and the O :7 (natural abundance) NMR spectra of a variety of substituted phenylisocyanates is reported (D.W. Boykin, Spectrosc. Lea., 1987, 20, 415). The mechanism and kinetics of cyclotrimerisation of arylisocyanates in the presence of base catalysts containing 4 ~ ammonium groups has been studied. (Y.M. Tsarfin, V.V. Zharkov and A.K. Zhitinkina, KineL Katal., 1988, 29, 1238; A.V. Selivanov et al., ibid., 1988, 29, 586; K. Matsunaga and Y. Yameshita, Toyo Daigaku Kogakuku Kenkyu Hokoku, 1985, 21, 57).

88

A new reaction of arylisocyanates with nitrite anion is described (N.P. Botting and B.C. Challis, J. Chem. Soc., Chem. Commun., 1989, 1585). 1,3Diaryltriazcnesare obtained via an intcnne~ate aryldiazotatcion. Ar-I~--C=O f O-NO

O Ar_ N_JNO O=N'J

Ar-..-N=N-O

O Ar-N=C=O

At- -N~~N,O

Ar- N=N=N-Ar

H+

Ar--~-N=N-Ar

The reaction of phcnylisocyanate with n-butanol in the presence of 3 ~ amines has been studied kinetically as a model process for polyurethane formation (R. Bacaloglu et al., J. Prakt. Chem. 1988, 330, 530). The rate determining step is the nucleophilic attack of the 3~ amine on the association of isocyanate with the alcohol forming a very reactive uronium salt. In the presence of tin compounds, rather than amines the rate determining step is the transfer from tin to isocyanate of alkoxide (idem, ibid., 541). Phenylisocyanate undergoes a wide variety of cycloaddition and cyclocondensation reactions and is useful for the synthesis of various heterocycles. Reaction with 1,1-dimethyloxirane gives a dioxolan-2-imine which rearranges to an oxazolidin-2-one (A.Baba and K. Seki, J. Heterocycl. Chem., 1990, 27, 1925). Enamines give azetidenones (C. Nisole et al., J. Chem. Res. Synop. 1991, 204). Reaction with vinylcycloproanes under palladium (0) catalysis leads to pyrrolidinones (K. Yamamoto, T. Ishida and J. Tsuji, Chem. Lett., 1987, 1157) and cycloaddition to iminophosphoranes leads to carbodiimides (H. Seifert, R. Noack and K. Schweflick, Z. Chem., 1990, 30, 368; P. Molina, M. Alajarin and A. Vidal, Tetrahedron, 1990, 46, 1063; P. Molina, E. After and A. Lorenzo, ibid., 1991, 47, 6737). Cyclocondensation of phenylisocyanate with ketene S,N-acetals leads to pyrimicliones (M. Gelbun and D. Martin, J. Prakt. Chem., 1987, 753, 329). 2Isocyanotobenzoyl chloride is a useful reagent for the elaboration of heterocycles (B.P. Acharya and R.Y. Rao, J. Sci. Ind. Res. 1988, 47, 152). The laser induced fluorescence UV specman of phenylisocyanate is due to the phenyl nitrene radical (G. Hancock and K.G. McKendrick, J. Chem. Soc., Faraday Trans 2, 1987, 83, 2011) although the signal long attributed to triplet phenylnitrene has unambiguously been shown to be due to the

89 cyanocyclopentadienyl radical (by rearrangement of "hot" phenylnitrene radical and a second photolysis, D.W. Oallin et al., J. Phys. Chem., 1990, 94, 8890; T. Ishida et al., Chem. Phys. Lea., 1990, 425, 170; 1988, 249, 150). 10. N-Arvlureas (a) Preparation N,N'-Diarylureas are available via the reductive carbonylation of aromatic nitro-compounds (A. Bassoli, B. Rindone and S. Cecini, J. Mol. Catal., 1991, 66, 163; 1990, 60, 155). A non-phosgene route for the synthesis of symmetrical NN,N~'diethyldiphenyl urea involves the condensation of aniline with urea and subsequent phase-transfer alkylation of N,N'-diphenylurea with diethyl sulfate (N.R. Ayyangar et al., Chem. Ind., 1988, 599). (b) Properties and Reactions The computational analysis of the crystal structure of N,N'-diphenylurea in relation to hydrogen-bonding is reported (J.S. Murray et al., Mol. Eng., 1991, 1, 75). The transamination of symmetrical diarylureas with diisobutylamine is descdbe~ (A.L. Chemiskyam, W.D. Gulyaev and V.T. Leonara, Zh. Org. Khim., 1988, 24, 2047) and the nitrosation of some N-phenylureas has been the subject of a kinetic and mechanistic study (A. Castro et al., J. Chem. Sot., Perkin Trans 2, 1988, 2021; 1987, 1759; 1986, 1725). It is suggested that the N-nitroso compound is formed via an initial O-nitrosation step, followed by rate-controlling loss of proton and that two parallel reaction paths operate, one being the reversible formation of the N-nitroso compound the other being irreversible formation of benzenediazonium ion, the only product from this reaction. N,N'-Diphenylurea undergoes a variety of cyclocondensation reactions. Reaction with benzoin leads to imidazolinones (M.H. Chawla and M. Pathak, Tetrahextron, 1990, 46, 1331). Photo-oxygenation of these intermediates in the presence of methylene blue leads to diacylureas. Similarly reaction with hydroxybutanones in the presence of CsF leads to oxazolidones (S. Sebti and A. Foucaud, J. Chem. Res. Synop., 1987, 72). 11. N-Arvlcarbamates (a) Preoaration N-Arylcarbamates are normally available via the reductive carbonylation of nitroarenes in the presence of alcohols (CA, 1990, 113, P152057p; 1989,

90 111, P239; 1987, 106, P32090c) but may also be manufactured via the alcoholysis of N,N-diphenylurea (CA, 1987, 107, P96448d, P96446b). N-Alkylation of N-arylcarbamates under phase-transfer conditions has been described (Kh. M. Shakhidoystov, D.N. Rakhimov and N.P. AbduUaev, Dokl. Akad. Nauk. UzSSR, 1988, 33). N-Alkylation of ethyl phenylcarbamate by 1,4--dichlorobut-2-ene is the first step in a stereospecific synthesis of Naryloxazolidinones, e.g., Toloxatane, which are analogue inhibitors of monoamine deoxygenase (J.P.Genet et al., Tewahedron Lea., 1990, 31, 515). (b) Properties and Reactions The structure-activity relationship of 69 substituted methyl, N-phenyl carbamates as fungicides has been considered (J. Takahashi et al., Pestle. Biochem. Physiol., 1988, 30, 262). The condensation of alkyl N-phenyl carbamates with methylenating agents such as formaldehyde has been much studied, since thermal decomposition of the resulting oligo/polymeric methylene bridged phenyl carbamates leads to isocyanates, useful for the preparation of polyurethane elastomers (CA, 1991, 115, P279615r, P71159n; 1990, 112, P180045f, P36704c; 1989, 109,

P191051u) The kinetics of reactions of urethanes with isocyanates, leading to aUophanates, have been analysed (L.V. Rakhlevskii, L.A. Bakalo and V.M. Fedorchenko, Kinet. Kaml., 1988, 29, 1062). The mechanism of thermal degradation of diphenyl alkyl allophanates has been studied providing a model for the cross-link sitesin polyurethane networks under thermal decomposition (M. Furukawa, N. Yoshitake and T.Yokoyama, Polyax Degrad. Stab., 1990, 29, 341). Reaction of methyl N-arylcarbamates with phosphorus pentachloride, or phosphorus oxychloride, at 140~ leads to N-arylisocyanates (D.N. Rakhimov, N.P. AbduUaev and K.M. Shakhidoyatov, Zh. Org. Khim., 1989, 25, 885). The sodium reduction and photoreduction of some arylcarbamates in the presence of HMPT has been considered.and the various competing reactions for both reaction conditions have been identified (A. Denbele, H. Deshayes and J.P. Pete, Bull. Soc. Chirn. Ft., 1988, 671). The interaction of alkyl phenylcarbamates with eerie ammonium nitrate provides an initiator for the free-radical polymerisation of acrolein (Z. Zhang et al., Gaofenzi Xuebao, 1990, 233). Nuclear benzoylation of methyl N-phenylcarbamate using (trichloromethyl)benzene in the presence of aluminium trichloride proceeds in

91 very high yield and has synthetic utility for the preparation of diaminobenzophenones, including the antithelmintic mebendazole (N.R. Ayyangar et al., Synthesis, 1991, 322 ; Org. Prep. Proced. Int., 1991, 33, 6271). Alkyl N-alkylarylcarbamates have herbicidal and fungicidal activity (K.F. Barnes, I.R. Browning and N.G. Clark, Pest.Sci., 1988, 23, 83). 12. ~-Arylcarbodiimides Symmetrical d i a r y l c ~ d e s are prepared from iminophosphoranes and carbon disulfide (N. De Kimpe et al., Org,. Prep. Proced. Int., 1982, 14, 213; Synthesis, 1982, 596). Treatment of thioureas with dipyridyltl~'onyl carbonate in the presence of DMAP also affords unsynmaetrical carbodiimides (S. Kim and K.Y. Yi, Tetrahedron Lea., 1985, 26, 1661). 13. Fl-Arylisocyanides Isocyanides can be prepared by the electrochemical reduction of caflxmimidoyl dichlorides ( A. Guirado et al., ibid., 1992, 33, 4779). PhN=CCh

e

,

phN=_.C

A general method for the preparation of o-diisocyanoarenes depends upon the dehydration of the corresponding formamides with trichloromethyl chloroformate (Y. Ito et al., Synthesis, 1988, 714). 14. lq-Arylisothiocyanates N-Arylisothiocyanates can be prepared by the base catalyse~ decomposition of methyl N-aryldithiocarbamates (C.S. PaL I.K. Youn and Y.S. Lee, ibid., 1982, 969). Treatment of N-aryldithiocarbamic acid tdethylammonium salts with triphenylphosphine and triethylamine in CO 4 also leads to Narylisothiocyanatcs ( I. Furukawa, N. Akr and S. Hashimoto, Chem. Express. 1988, 3, 215). Metathesis of aryl isothiocyanates has been used in a novel synthesis of st~cally hindered arylisothiocyanatcs ( N.S. Habib and A. Ricker, Synthesis, 1984, 825).

92 15. N-Arvlamides of Sulfur Acids The chemistry of the N-arylamidcs of sulfuracids is dcscribe~ in more general reviews contained in the three volumes of "The Chemistry of the Functional Group: The Chemistry of Sulfonic Acids, Esters and their Derivatives"; and "The Chemistry of Sulfenic Acids, Esters and their Derivatives"; as well as "The Chemistry of SulfinicAcids, Esters and theirDerivatives" (Eds. S. Patai and Z. Rappoport, Wiley Intcrscience,Chichestcr, N.Y. 1990, 1991).

Sulfamic acids The first isolation and characterisation of free phenylamidosulfuric acid, an intermediate postulated in the sulfonation of arylamines, is describe~. The phenyhmidosulfin'ic acid is prepared by adding concentrated. HC1 to a cold aqueous solution of the corresponding ammonium salts. They are zwitterionic, non-hygroscopic, crystalline solids that are stable at room temperature (F. Kanetani, Chem. Lett., 1980, 965).

Sulfenamides N-(4-Nitrophenylthio)-2,4,6-tri-t-butylphenylaminyl radical is prepared by oxidation of the corresponding sulfenamide with PbO2/K2CO 3 in benzene under nitrogen (Y. Miura et al., J. Chem. Soc., Chem. Commun., 1980, 37). The chemistry of sulfenamides is specifically reviewed (L. Cmine and M. Raban, Chem. Rev. 1989, 89, 689; I.V. Koral, Usp. Khim., 1990, 59, 681).

N-Thiosulfinylanilines The reaction of 2,4-di-t-butyl-6-methyl-N-thiosulfmylaniline with various electrophiles such as mCPBA and bromine has been investigated.(Y. Inagaki, R. Okazaki and N.Inamoto, Bull. Chem. Soc. Jpn., 1979, 52, 3615).

Sulfur Diimides The synthesis of diphenylsulfur diimide from N-sulfinyl~iline using a nickel (0) catalyst has been describeA (D. Walther, E. Dinjus and H. Wolf, Z. Chem., 1979, 19, 381). 16. N-Arvlamidcs of Phosohorus A~ids The chemistry of N-arylamides of phosphorus acids is described in more general reviews contained in the series Royal Society of Chemistry, Specialist Periodical Reports: Organophosphorus Chemistry, Volumes 13-24.

Phosphazenes The increasing importance of these intermediates is highlighted by the emergence of a fullchapter in the above publication.Readily availablevia the Staundingcr reaction, N-arylphoshazcncs are pcrphaps most commonly used in aza-Wittig reactions leading to hetcrocycles.

93 The NMR (31p, 15N, 13C) and cyclic voltammetry of substituted Narylphosphazenes have been studied with respect to substiment effects and their correlation with molecular orbital calculations. (M. Pomeranz et al., J. Org. Chem., 1986, 51, 1223). A compound containing the first stable P-N triple bond is reported (E. Niecke, M. Nieger and F. Reichert, Angew. Chem. Int. Ed. Eng., 1988, 7, 1715).

This page intentionally left blank

Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds, Vol.lll B, C,D(Partial), edited by M. Sainsbury

95

9 1995 Elsevier Science B.V. All rights reserved.

Chapter 10

AROMATIC COMPOUNDS OF THE NON-TRANSITION METALS

Stephen T. Mullins

1.

Introduction

Main group organometallic chemistry has continued to expand during the past decade and progress is mirrored by the publication of several reviews, as detailed annually in Organometallic Chemistry and Royal Society of Chemistry Annual Reports A. New text books include 'Organometallic Chemistry', A.W. Parkins and R.C. Poller, Macmillan Publishers Ltd, Hong Kong, 1986 and 'Chemistry of the Metal-Carbon Bond', vol 4, ed. F.R. Hartley, John Wiley & Sons, 1987, which focus primarily upon the use oforganometallics in synthesis and 'Principles of Organometallic Chemistry', Second Edition, P. Powell, Chapman and Hall, New York, 1988, which considers in detail the structure of organometallics as well as their use in synthesis and general chemistry.

2.

Group 1 Metals

2.1

Lithium

The preparation and use of aryl organolithium derivatives in synthetic

96 chemistry is now standard practice. Reviews have been published covering nitrogen and oxygen assisted lithiation (G.W. Klumpp, Recl. Trav. chim. PaysBas, 1986, 105, 1). The classical halogen-lithium exchange method for the preparation of aryllithium reagents (H. Cfilmanand A.L. Jacoby, J. org. Chem., 1938, 3, 108) has been applied to the preparation of aromatic organolitium reagents bearing electrophilic groups (W.E. Parham and C.K. Bradsher, Ace. chem. Res., 1982, 15, 300). Benzene is dilithiated efficiently using a combination of n-butyllithium and hydrocarbon soluble potassium tert-alkorddes (L. Lochmann, M. Fossatelli, and L. Brandsm, Recl. Trav. chim. Pays-Bas, 1990, 1.09, 529) for example MeaCEtOK, Et2CMeOK or Et3COK. A solution of n-butyl lithium in hexane is added to benzene, followed by a heptane solution of the potassium tertalkoxide in the temperature range -10 to -40~ This results in the formation of a mixture of mono- and dimetallated benzenes which can be quenched by adding dimethyl sulphide. Results for a variety of conditions are shown in table 1. Benzene dianion (1) (scheme 1) is also obtained by the reduction of hexakis(trimethylsilyl)benzene (2) using excess lithium metal in tetrahydrofuran (H. Sakurai et al., J. Amer. chem. Soc., 1991, ! 13, 1464).

_ SiMe3 Me3Si~

SiMe 3

SflVIe3

MeaSiF ~-~~ S i M e 3 SiMea

Li THF

(2)

Me3S~~

S~'Ie3

Me3Si-- ~-~~ S i M e 3 SiMe3 (i)

Schen~1

2+

[L~r~)]2

97 ,,

.

.

.

Bases

.

,

.

.

,

Equiv. of the Base

,,

Reaction time (h) at 20~

Yield PhSMe

Yield C6H4(SMe)2 t

BuLi and KOCMe2Et

2and2

1.5

45

47

BuLi and

2and2

3

45

49

BuLi and KOCMe2Et

8and8

2

17

81

BuLi and KOCMe2Et

2and6

1.5

50

35

BuLi and KOCEtzMe

2 and 2

2

33

48

BuLi and KOCEt2Me

4 and 4

2

32

57

BuLi and KOCEt3

2 and 2

2

25

46

BuLi and KOCEta

2and2

2.5

20

55

BuLi and

2 and 2

2.5

46

30

K0CM,Et

i

KOCMe, BuLi and

,

3 and3

34

,

,

,

27

KOCM, Table 1 Formation of mono- and dimetallated benzene from mixtures of potassium tert-alkoxides, n-butyllithium and benzene

98 The dianion (1) when generated at room temperature in oxygen free THF imparts a dark red colouration to the solution and is isolated as red crystals from hexane. As would be expected the dianion is very susceptible to oxygen and water and readily reverts to the silyl derivative (2) in contact with air. Reaction of (1) with water results in the formation of 1,2,3,4,5,6hexakis(trimethylsilyl)cyclohexa- 1,4-diene (3) (scheme 2). H

S~Nle3

Me3Si

SiMe 3

I-I20 (1) Me3Si"

/~

Me3Si

"SflVIe3 H

(3) Scheme 2 The most interesting feature of the structure of (1), as determined by X-ray crystallography, is that the Li ions are situated on the same side of the benzene ring, and despite electrostatic repulsions, are only 2.722 A apart. This structure is different from those previously reported for polynuclear aromatic dianions where the cations are above and below the plane of the aromatic ring, for example in the lithiation complexes of naphthalene, anthracene and fluorene (J.J. Brooks, W. Rhine, and G.D. Stucky, J. Amer. chem. Soc., 1975, 94, 7339, and 7346, and W.E. Rhine, J. Davis, and G.D. Stucky, J. Amer. chem. Soc., 1975, 97, 2079).

99 A structural determination of the 10~x electron dianion dilithium pentalenide (4) shows the two lithium cations to be on opposite sides of the aromatic dianion (P. von Ragu~ Schleyer et al., Chem. Comm., 1985, 1263). This agrees with MNDO calculations which also favour this opposite arrangement of metal ions. The two lithium ions are 115 and the five possible arrangements are shown in figure 1. Structure (4) is 5 kcal mol1 more stable than its nearest rival and at least 20 kcal mol q more stable than the others.

Li

Li A HtO = 9.4 kcal mol- 1 (4) Li

Li

Li A HtO =30.7 kcal mol- 1

AHtO = 14.4 kcal mol- 1 ,,,,L.i

.,,"Li

A Hto = 43.5 kcal mol- 1

A HtO = 39.5 kcal mol- 1 Figure 1

100 Aryllithium and aryl-metal-lithium clusters of the general formula AraM2Li2 (M = Cu, Ag, Au) have been prepared and their structures assigned by X-ray crystallography (G.van Koten and J.G. Noltes, J. Amer. chem. Soc., 1979, 101, 8593). These clusters have polynuclear structures with a metal core to which each of the aryl groups is bound by a three-centre two electron bond to two metal atoms. For example the structure of (2-Me3NCH2C6Ha)aM2Li2 is shown in figure 2.

Li

Me2

Me~

Figure 2 If the complexes of the type Ar4M4 and Ar4U2Li2 contain unsymmetrical aromatic groups, then they can exist as four unique stereoisomers which can be detected by proton n.m.r, spectroscopy. When the C(1) carbon of an asymmetrically substituted aromatic ring bridges two dissimilar metals then it becomes a centre ofchirality. Two such situations can occur; a) when the two metals bridged are not the same i.e. Cu and Li, or b) when the metal atoms are the same but differ in their coordination geometry. Again these isomers can be distinguished by proton n.m.r.

101 Other cluster organometallics of lithium which comain multicemre bonds have been reported such as intramolecularly chelated di and tetranuclear aryllithium compounds for example Li4[C6H4(2-CH2NMe2)]4 (G. van Koten, J. Amer. chem. Soc., 1982, 104, 5490). The structure of this compound, as determined by X-ray crystallography, contains four-cemre-two-electron=bonded C(aryl) atoms and hepta coordinate lithium atoms as shown in figure 3.

Li -~"

"-" '%~t, .

Mo,i Figure 3

This cluster was prepared by slow crystallisation from an ether-hexane solution containing an exact equimolar mixture of n-butyllithium and N,Ndimethylbenzylamine (scheme 3). CH2NMe2

CH2NMe 2

Et2o 4

+

Li

4 BuLi -BuH Scheme 3

-4

102 Other mixed metal organometallics containing lithium have been prepared, for example phenyl and p-tolyl-iron-lithium trans dihydrides (A.E. Silov et al., J. organomet. Chem., 1992, 428, 107). The action of excess phenyllithium on iron(II) chloride gives a zero valent iron complex [FePh4]Li4.4Et20 (A.E. Shilov et al., 1983, 244, 265) which reacts with nitrogen to produce a new iron-lithium complex containing dinitrogen coordinated to iron. A similar dihydrogen complex is formed when [ F e m r 4 ] L i 4 . 4 E t 2 0 , where Ar is phenyl, mor p-tolyl, interacts with hydrogen. Binuclear complexes are formed by interaction of the trans dihydride complexes with solvents such as diethyl ether and THF. Scheme 4 shows how the mixed metal complexes are formed. -30oc 7 PhLi + FeC13

[Li4FeIIph6] + 3 LiCI + 0.5 Ph 2

Et20 20oc

[Fe0ph4]Li4 . 4 Et20

+ ek2

Scheme 4

Both the Feu and Fe~complexes react readily with hydrogen to give dihydrides as well defined dark crystals. Infra red spectroscopy and X-ray crystallography reveal that the Fe n complex dihydrides show a central oetahedral unit Ar4FeH2with the hydrogens trans at the Fe atom. Fe-H bond lengths are typical of iron hydrides, and the i.r. stretching frequency for the Fell bond is about 1200 em"~. Although the preparation of the m-tolyl complex is successful, the o-tolyl and mesityl complexes can not be prepared, presumably due to sterir hindrance of the ortho-methyl groups.

103 Reactions of these iron complexes with hydrogen are carried out at room temperature. Reaction of the p-tolyl complex is complete within 3 hours whereas the m-tolyl complex takes 24 hours. This difference in reactivity is explained by steric hindrance to cis-trans isomerisation in the dihydride complex. It is evident that the cis-dihydride must form first, followed by isomerisation to the more stable trans isomer. This isomerisation requires the bending of the Fe-Ar bond, which is hindered by adjacent methyl groups. Mixed metal organometallics containing lithium and tin have been proposed as intermediates in lithium-tin exchange reactions used for the preparation of organolithium derivatives when more robust methods are not mild nor selective enough (H.J. Reich and N. Phillips, Pure and Applied Chem., 1987, 59, 1021 and J. Amer. chem. Sot., 1986, 108, 2102). Functionalised organolithium derivatives bearing electrophilic groups are regularly synthesised by this exchange method. The proposed intermediate is a pentavalent tin "ate" complex (5) based on kinetic studies and spectroscopic, mainly n.m.r., characterisation of lithium pentaarylstannate complexes.

Li+

R' .I..R R-~-~ R

R

(5) 1-Methyl-2-(methylthio)benzene (6) when treated with two equivalents of nbutyllithium in the presence of N,N,N',N'-tetramethyl-l,2-ethanediamine (TMEDA) gives the dilithio compound (7) (S. Cabiddu, C. Floris, and S. Melis, J. organomet. Chem., 1989, 366, 1).

104

M0 (e

c,~...sH2cLiH2Li

2 n-BuLi

SMe

(6)

(7)

When the methyl group in (6) is meta or para to the methylthio group the second lithiation does not occur at the benzylic position but ortho to the methylttfio group. The benzylic metallation of (6) can be explained in terms of methyl thio group metallation, aided by the unoccupied d orbitals on sulphur, followed by metallation of the benzylic position. The latter is mediated by interaction of the negative sulphur atom with a second molecule of butyllithium (8).

CH2 ' s~Li"'Bu I

CH2Li (8) Scheme 5 details the products from quenching the dilithium derivative (7) with eleetrophiles. Attempts to form a dicarboxylic acid by reaction

105 Et

~SE,

T /i

~

CH2CH2CH=CH2

"

'SCH2CH2CH=CH2

2 MeI

2 CH2=CHCH2Br

2 Me3SiCI (7)

sc,~/

PhCOCl

I CO ~SS

~S

(9) OLi (7)

2 CO2 +

0o)]

~

O

(11)

OLi H+

(9) Scheme 5

106 with carbon dioxide result in very low yields of the acid together with the sulphur heterocycle (9) which is formed in about 50% yield. Formation of (9) can be explained by addition of one molecule of CO2 to give intermediate (10) or (11), followed by intramolecular addition of the second lithiated site to the carbonyl function of the monoacid. This reaction is unusual in that it occurs when there is an excess of CO2. Normally this type of cyclisation only takes place when there is a deficiency of CO2. The dilithiated derivative (7) resists attempts to introduce regioselectively two different functional groups. For example, treating (7) with one equivalent of methyl iodide followed by an excess of methanol results in the formation of an equimolar mixture of (12) and (13).

Et

~ S M e (12)

,Me

~~I~SEt (13)

Reactions of the lithio derivative (7) with gem-dihalides provide useful routes to benzo-eondensed six membered heteroeylees, containing sulphur and one other heteroatom (scheme 6).

107 Me ;LMe ~ kS~ C l 2 p h

Me

2SIC12 [~s~Si~,,M~h

s~t~

/ph

Scheme6 Reaction of 1-bromo-2-[(trimethylstannyl)methyl]benzene(14) with n-butyl and tert-butyUitl,fium leads to 1-bromo-2-(lithiomethyl)benzene(15) and 1lithio-2-[(trimethylstannyl)methyl]benzene(16) respectively (H.J.R. de Boer, O.S.Akkermen, and F. Bickelhaupt, Organomet., 1990, 9, 2898). nButyllithiumeffects a lithium-tin exchange whereas tert-butyllitMum reacts by the more conventional lithium-halogen exchange process. The dilithiated derivative ~,2-dilithiotoluene (17) has also been prepared by reaction of (16) with tert-butyllittfium.

108 This remarkable selectivity is explained by making the following assumptions: i) lithium-tin exchange is faster than lithium-halogen exchange under identical conditions, ii) lithium-tin exchange is more sensitive to steric hindrance than lithium-halogen exchange, iii) exchange of both tin and halogen is retarded by the presence of electron donating substituents. Scheme 7 shows how these assumptions are applied to the selectivity of reactions of n- and tertbutyllithium with (14).

m

~

SnMeanB ~70~ ~ S n M e 3 ,r

j

tBuLi -70~ ow ls - ~

SnM3e

fast L 1

(14)

(16)

tBuLi I very .70Oc ', sbw

lBuLi I fist 25~ _

~

SnMe3tBu L~ ~ L i

(15)

SnMe3tBuL~ (18)

~~Li (17)

Scheme7

Li

109 n-Butyllithium is sterically undemanding and reacts by lithium-tin exchange (bearing in mind assumption i). Further reaction with n-butyllithium to give the dilithiated derivative (16) is strongly retarded by the presence of the benzylic carbanion, tert-Butyllitl,fium is much more sterically demanding than its n-butyl counterpart and so it reacts via lithium-halogen exchange to give (16) (N.B. assumption ii). Only when the temperature of the reaction is increased to 25~ does the lithium-tin exchange reaction take place to give the much more sterically congested stannate complex (18). This loses trimethyltert-butylstannane to give (17). 2.2

Sodium, Potassium, Rubidium, C~esium

Much less has been reported during the past decade regarding the heavier Group 1 metals. The reaction of organolithiums with heavier alkali metal alkoxides generates an aryl compound of the heavier alkali metal and lithium alkoxide (L. Lochman, J. Pospisil, and D. Lim, Tetrahedron Letters, 1966, 257 and L. Lochman and D. Lim, Organomet. Chem., 1971, 28, 153). When toluene is introduced as a third component to this reaction benzylpotassium is formed in good yield. Likewise when benzene is added phenylpotassium is produced (scheme 8) (L. Lochman, Coll. Czech. chem. Comm., 1987, 52, 2710).

+ RLi +

. M~

+ RH + OK

M~

OLi

K Scheme 8 Arylsodium derivatives can be prepared by a similar reaction of sodium alkoxides with aromatics and alkylithium derivatives. This reaction forms the

110 basis of a method for the facile coupling of non-activated aromatics (L. Lochman and J. Trekoval, Coll. Czech. chem. Comm., 1986, 51, 1439). When aryl bromides or iodides are added to the reaction mixture containing sodium or potassium alkoxide and butyllithium, the major organic reaction products are those due to coupling (scheme 9).

E. f ~ . Me + KBr + Me:

_.•.

Me

+ BuLi + OK

Me?

Br

OLi

Bu

Scheme 9 The reaction of potassium hydride with PfiMe2SiOH, followed by crystallisation of the product from benzene results in [(C6H6)KOSiMe2Ph]4. This complex has been characterised by elemental analysis, proton n.m.r., 29Si n.m.r, and its structure elucidated by X-ray crystallography (K.G. Caulton et al., Polyhedron, 1991, 2371). The complex is interesting due to the rl 6 bonding of the benzene to potassium. The benzene ring binds to potassium via its n-system as there are no better donors available in the complex. Here such bonding can occur without the back bonding found in transition metal arene complexes. The complex K2[la-N(SiMe3)2]22toluene also exhibits rl6-arene binding to potassium, and solutions of alkali metal compounds with low coordination numbers, in benzene are also likely to exhibit this type of arene/potassium binding. This shows that a hard Lewis acid such as K + has an affinity even for as soft a donor as the n-arene system. Arylsodium and potassium derivatives can be solubilized in benzene by the addition of magnesium 2-ethoxyethoxide (C.G. Screttas and M. MichaScrettas, Organometallics, 1984, 3, 904). One reason for the limited synthetic use of arylsodium and potassium derivatives is their intractability, they are

111 insoluble in solvems in which they might survive long enough to be useful. Organosodium and potassium derivatives do have certain advantages over the more ot~en used organolithium derivatives in that they are more reactive and so they do not require a Lewis base catalyst in order to effect more difficult metallations (C.G. Screttas and J.F. Eastham, J. Amer. chem. Soc., 1965, 87, 3276). The orientation of metallation is metal dependant (M. Schlosser and P. Schneider, Helv. 1980, 63, 2404) thus having a selection of Group 1 metal aryl derivatives, which are hydrocarbon soluble, would be a useful tool for any synthetic chemist. Scheme 10 shows the reaction of arylalkalimetal reagents with magnesium alkoxides. The resulting complex is quite stable in benzene for long periods of time at 13-22~ but at higher temperatures crystalline precipitates form.

nArM + mMg(OR)2

~

(ArM)n[Mg(OR)2]m

Scheme 10

The solutions exhibit normal organometallic reactivity towards carbon dioxide and benzophenone, and phenylsodium and potassium complexes effect metallation in the same way as organometallic reagents. For example they metallate toluene and dibenzofuran readily and react with thioanisole to metallate the methyl group. Arylc~esium derivatives are extremely reactive and of little synthetic use. Aryl complexes of c~esium of the type Cs[AI(CH3)212]:C6H4(CH3)2 have been prepared and their crystal structures reveal that the c~esium ion is sandwiched between two p-xylene molecules with an average Cs-C bond distance of 3.83A. The c~esium ion also has four iodine atoms within bonding distance, 3.925~, (Figure 4) (RD Rogers and J.L. Atwood, J. Cryst. tool. Structure, 1979, 9, 45).

112

o

~

o o = carbon

0

0

6b

db

O0

= iodine

O0

b ~

o

Caesium environment in C s[Al(CH3)212] P-C6H4(CH3)2 Figure 4 Potassium analogues of these complexes show a much stronger bonding interaction as revealed by rather shorter metal-carbon bond distances. The average K-C distance is in these complexes is 3.36A (J.L. Atwood, K.D. Crissinger, and R.D. Rogers, 1978, 155, 1). The reaction of benzene with CSC24results m an intercalation compound in which each c~esium is surrounded by two benzene tings, tilted at 36 ~ to the c axis (P. Touzain and A. Hamwi, Materials Science and Engineering, 1991, a l 0 , 275).

3.

Group 2 Metals

3.1

Beryllium, Magnesium, Calcium, Strontium, Barium

The chemistry of Grignard reagents is well established as is that of the corresponding beryllium analogues. Many reviews and papers have been published on these compounds and their chemistry. The preparation of highly functionalised aryl organometallics is of great

113 interest due to their versatility as reagents in the preparation of a wide range of highly functionalised organic molecules (see for example, S. Achyutha-Rao and P. Knochel, J. Amer. chem. Soc., 1991, 113, 5735 and H. Tsujiyama et al., Tetrahedron Letters, 1990, 31,4481). The preparation of these highly functionalised organometallics, which contain eleetrophilic groups, is not, however, straightforward as direct metal insertion is often difficult and can lead to mixtures of products. It has been reported that functionalised aryUithiums can be used to prepare organometallic derivatives of magnesium, zinc and copper. Functionalised aryl halides (19) can be converted in organolithium derivatives (20) by slow addition of butyllithium to the arylhalide at -100~ (scheme 11). Addition ofMgBr2, ZnI2, or CuCN:2LiCI to the organolithium at -100~ results in a transmetallation and furnishes more stable highly functionalised organometaUics (C.E. Tucker, T.N. Majid, and P. Knochel, J. Amer. chem. Soc., 1992, 114, 3983).

Y

y

Y

BuLl (1.5 eq) ,

X

~

~'~

- 100 oc 3 nimaes IHF

(19)

Li

ZnI2 or MgBr2 or CuCNLi or C uCNZnX

(20)

Y = CO2R, CN, CI, N 3, NO2 X=IorBr M = Z.n.I,MgBr, CuCN Scherr~ 11

M

114 Various eylopentadienyl magnesium complexes have been prepared by the reaction of dibutylmagnesium with eyelopentadienes (M.F. Lappert et al., J. organomet. Chem., 1985, 293,271). Such magnesium complexes are useful as mild ligand transfer reagents as is illustrated by the synthesis of Zr(CsH3Xz)C13, where X is H or SiMe3. An unusual reaction of aryl Grignards is that with (NPCI/)3 (21) which gives arylcyclotriphosphazines (22) and bis(arylcyclotriphosphazines) (23) (scheme 12) (H.R. Allcock, J.L. Desoreie, and P.J. Harris, J. Amer. chem. Soc., 1983, 105,2814).

CL\ / CI N~PxN CI~P~N/P~CI c/

Cl

(21)

PhMgBr

Ph_\ / CI N~PxN CI----~,,~N/P~Ph Ph

CI

(22)

Ph_-'___~P~N Cl p h ~ ~ ' N ~' " P h C1 (23)

Scheme 12 The mechanism of this reaction has been studied it seems that (22) and (23) are not related and form independently. In the case of (23), coupling of a monomeric cyclophosphine is implicated (scheme 13). Oxidation and reduction potentials of reactants have been correlated with product distribution in the reaction of various organomagnesium reagents with aromatic earbonyl and nitro compounds (M.Okubo, T. Tsutsumi, and K. Matsuo, Bull. chem. Soc. Jpn., 1987, 60, 2085).

115 CI\ /C1

CI\ /R

N~P~N

N~PxN

Cl--~. N/P----CI CI CI (21)

C1 (22)

t

-RCI

CI\ N/I~NIMgX l)

CI

l

R

R\ ,

N/I~N.~-MgX

~VlgX

II

r

I

CI

CI

Cl (22)

CI\ /CI CI\ /CI N~pxN N/P~N I

II

II

I

CI---'~',~N/P~ ~-N ~'P~- C I C1 RR C1 (23)

Scl'~'n~13

116 The electron-donating ability (EDA) of a series of Grignard reagents and the electron-accepting ability (EAA) of various arylnitro and carbonyl compounds have been detem~ed by cyclic voltametry. The relative efficiency of electron transfer in individual reactions is dependent on the combination of EDA and EAA values, a correlation can then be made between the distribution of normal and abnormal (free radical) products and AE, the difference between EDA and EAA. It is found that in reactions where AE is small, typically less than 2.2, high yields of products due to free radicals reaction are obtained; vigorous electron transfer occurs in these reactions. For cases where the AE value is 2.2 -2.8, good yields of normal products, in most cases above 65%, are obtained as the electron transfer process is subdued. Arylcalcium derivatives are far less well understood than their beryllium and magnesium counterparts principally due to their reactivity and difficulty of synthesis. Metal vapour reactions of calcium with aromatic compounds to give arylcalcium derivatives has been studied (K. Mochida et al., Organometallics, 1987, 6, 2293). Calcium is generated by vaporisation from a tungsten filament at 20 mg minq while an excess of the aromatic compound is co-condensed on the walls of a quartz reaction vessel. Arylcalciums are obtained as black solids in which the calcium atom is inserted into the C-H bond. They are very reactive and combine with electrophiles with ultimate displacement of calcium ion (scheme 14).

Ca(g)+ ~

(g) 77K

(24) Schen~14

ii)1-/20

S~/Ie3

117 3.2

Zinc, Cadmium and Mercury

Benzyllithium and magnesium compounds are otten difficult to prepare by conventional methods and decompose to give cross-coupled products even at low temperatures. Benzylic derivatives of zinc, however, can be prepared in high yield with little evidence of cross-coupling (S.C. Berk, P. Knochel, and M.C.P. Yeh, J. org. Chem., 1988, 53, 5791 and T.N. Majid and P. Knochel, Tetrahedron Letters, 1990, 31, 4413). The reactivity of the organozinc derivatives (25) towards electrophiles is much increased by transmetallation to the copper containing organometallics (26) (scheme 15).

R

Br

~ X

R

ZaBr

Zn, TI-IF 0oc, 2-3h

R

.Cu(CN)ZnBr

CuCN.2IziC1~ X (25)

R

E

E X (26)

X

X = COR, OAc, CN. CI, I E = aldehydes,acidchlorides,enones,allylicbromides R= CH3, H

Scheme 15 This methodology has been developed for the preparation of polyfunctional organometallics bearing sulphur (P. Knochel et al., Tetrahedron, 1992, 48, 2025).

118 Regioselective addition of copper-zinc arylorganometallics to 3-substituted pyridinium salts results in the formation of predominantly 4-arylpyridines, especially if the substituent is electron donating (M-J. Shia0 et al., J. chem. Res (S), 1992, 247). Pyridinium salts with electron withdrawing groups at the 3-position tend to give mixtures of both 2- and 4-arylated compounds. The ratio of 4 : 2 substitution is between 2.5 : 1 and 4 : 1. Analysis of the lowlying vacant orbitals on the pyridinium ring predicts that sott nucleophiles should preferentially substitute at the 4-position. Since mixed copper-zinc aryl organometallics generally act as soft nucleophiles the prediction is fulfilled in practice. Electroreduction of aryl chlorides or bromides in a cell fitted with a sacrificial zinc anode, in the presence of nickel-2,2'-bipyridine complex results in the formation of the corresponding zinc organometallic in good yield (S. Sibille, V. Ratovelomanana, and J. Perichon, Chem. Comm., 1992, 283). Perfluoroaryl cadmium reagents (27) have been prepared, under mild conditions, by the direct reaction of bromofluoroaromatics with powdered cadmium (P.L. Heinze and D.J. Burton, J. fluorine Chem., 1985, 29, 359). Both the mono and bis(aryl) cadmiums are formed in the ratio 85 : 15.

C6H5Br + Cd X = Br, C6F 5

DMF, RT ~

[C6F5CdX] (27)

Regiospecifie monoacetoxymercuration of a series of aryl substituted thiazolines results in derivatives which have increased fungicidal activity (J. Mohanty and G.N. Mahapatra, Indian J. Chem., 1982, 52).

119 Mercury acetate has been used to effect cyclisations of ortho substituted arylacetylenes (28) to afford a variety of chloromercuryheterocycles (29) (scheme 16) (R.C. Larock and L.W. Harrison, J. Amer. chem. Sot., 1984, 106, 4218). The cyclisations are carried out at either 0 or 25~ in acetic acid, in the presence of sodium chloride.

X-oC_) ( y/C ~'CR

NaCI

(28)

Y

HgCI

(29)

X = O, S, CO 2 Y=-,CO Scheme 16 Mercury trichloroacetate can also be used to effect aryl mercuration (M. Niemyjska et al., Bull. Poilish Acad. Sci. Chem., 1990, 38, 1). Mercury trichloroacetate, prepared in situ from mercury(H) oxide and trichloroacetic acid, reacts with benzene in the presence of sodium chloride to afford phenylmercury chloride, rather than phenylmercury trichloroactate. Metal exchange reactions provide a general route to organomeeurials. Silatranes (30) react with mercury(H) chloride to yield arylmercury chlorides (J.D. Nies, J.M. Bellama, and N. Ben-Zvi, J. organomet. Chem., 1985, 296, 315).

120 ArSi(OCH2CH3)3N + HgCI2

-

=

ArrtgCl + XSi(OCH2CH3)3 N

(30)

Mercury(II) chloride also reacts with ortho-manganated arylketones (31) to afford arylmercury chlorides (J.M. Cooney et aL, J. organomet. Chem., 1987, 336, 293). Yields ofmercurated products are generally good, about 65%, and the transmetallation is specific to the position ortho to the acyl group.

HgCI

P'2

R2

(31) R1 = CH3, Ph R2 = H, OCH3

A similar transmetallation reaction occurs between the gold trichloride complex (32) and the mercury complex (33) (scheme 17). A further transmetallation of the resulting complex (34) occurs when it is treated with the bisarylmercury (35) in the presence of tetramethyl ammonium chloride (J. Vincetnte et al., J. chem. Soc. Dalton, 1990, 10, 3083).

121

AuCl3(tht) + Hg(C6H4N=NPh)2 CI/ (32)

Ncl

(34)

(33)

I HgR

--Ph R = p-NO2C6H4, or C6F5

/

R

tht = tetrahydrothiophene

Ncl

(35) Scheme 17

Arylmercuric halides react with with [Et3NH][(I,t-CO)(B-RS)Fe2(CO)6] to give bridged acyl complexes of the type (la-R'C=O)(la-RS)Fe2(CO)6 (D. Seyforth et al., Organometallics, 1991, 10, 3363). N.m.r. has been used to determine the structure of coordinatively unsaturated aryliridium(III) complexes which comain iridium-mercury bonds. In particular, mercury coupling in the 3,p n.m.r, spectrum of (36) confirms the presence of Ir-Hg bonding, J(3~p-~99Hg)= 204.5 Hz. (W.R. Roper and G.C. Saunders, J. organomet. Chem., 1991,409, C 19). Complexes of this type are prepared by the reaction of arylmercurials with IrHCI2(PPh3)3 (Scheme 18).

122 IrHCI2(PPh3)3 + Hg(o-tolyl)2 I Ben~ne, rettux, 1.5h, 20%

Ph3P. I ,,,5~'~

C1---Ir~'

(36) Reduced

--

Pressur~o,

1 atm

12 78% or N~C150%

PhaP CI,,.... .] ....... /

Ph3P

....

~.

INHgx PhaP ~X

/

X - I or C1 IrCI(CO)(PPh3)2 + Hg(tolyl)2 S c h e m e 18

123 Sustituent effects on ~99Hgchemical shit,s in bisarylmercurials has been studied (Y-J. Wu et al., Chem. Res. in Chinese Universities, 1992, 8, 81). In general electron donating substituents in the aromatic tings of bisarylmercurials cause a downfield shit~ of the ~gHg chemical shift. This occurs because there is an increase in the electron density in the 6pz orbital of mercury by p-n conjugation, which results in paramagnetic shielding.

4

Group 3 Metals

4.1

Boron

The degree of involvement of the available 2p~-orbital on the sp 2 hybridised boron in triarylborirenes has been investigated (J.J. Eisch et al., J. Amer. chem. Soc., 1990, 112, 1847). These boron containing analogues of cyclopropene are readily prepared by the photolysis of diaryl(arylethynyl)boranes (scheme 19). Mes\

hv B----C~C----Mes

Mes'/

~ donor solvent

MeS~C__C/Mes \ / B[ Mes

Scheme 19 Triarylborirenes are surprisingly stable despite their considerable ring strain. Stabilisation is afforded by extensive delocalization of the two n-electrons of the ring among the boron and carbon p-orbitals, and the ring can be said to have H0ckel aromaticity analogous to that of the triphenylcyclopropenium cation. The alternative valence bond description involves the canonical forms shown (scheme 20) with considerable electron density residing on boron.

124

Xc=c \/

ArXc_cr \\/

~

~

B

B-

\11 _B

Ar

Ar

Ar

I

I

I

Scheme 20 The aromatic nature of various three membered rings containing boron has been studied using ab mJtio molecular orbital methods (P.H.M. Budzelaar and P.vonR. Schlyer, J. Amer. chem. Soc., 1989, !08, 3967). The studies reveal that the 2r~-species (37) and its amino derivatives are planar and aromatic with a resonance stabilisation energy of 55 kcal mol~. Derivatives of the diazaboridine ring system (38) are antiaromatic 4r~ systems. However, amino substituents on the boron relieve this destabilising effect by electron donation.

H

I N

/\ H/B~B~H

(37)

H

I

/N\ H/N--B~H

(38)

The unsaturated B3P3ring system is also aromatic as indicated by the shortness (1.84 A) of the B-P bonds (P.P. Power, Pure and Appl. Chem., 1991, 63, 859 and H.V.R. Dias and P.P. Power, J. Amer. chem. Soe., 1989, 111, 144).

125 Pentaaryl boroles can be prepared by two routes, (i) the interaction of an (E,E)-( 1,2,3,4-tetraaryl- 1,3-butadien- 1,4-ylidene)dilithium with an aryl(dihalo)borane and (ii) the exchange reaction between a 1,1-dialkyl2,3,4,5-tetraarylstannole and an arylboron dichloride (scheme 21) (J.J. Eisch, J.E. Galle, and S. Kozima, J. Amer. chem. Sot., 1986, 108, 379). R

RC~-CR

R

'

Method (ii) Me2SnCI2 J R

Me

R

"Me

~ R

R

{

Method (i) RBC12 R

R.R

R

R

Scheme 21 Pentaaryl boroles are strong Lewis acids, they complex with amines, ethers and nitriles and are very prone to oxidation, solvolytic cleavage, and DielsAlder reactions. This high reactivity and their unusual proton n.m.r, and electronic spectra can be explained by considering them as Huckel antiaromatic systems, the destabilization arising from the interaction of the 4r~electron four carbon fragment and the 2p~ orbitals on the boron.

126

4.2

Aluminium

Aluminium is known to interact with benzene (R. Srinnivas, D. SOlze, and H. Schwartz, J. Amer. chem. Soc., 1990, 112, 8334) affording complexes which are easily studied by e.s.r spectroscopy. Theoretical methods have now been applied to these complexes in order to establish their structure (M.L.McKnee, J. phys. Chem., 1991, 9_5, 7247). Figure 5 shows the three possible modes of interaction of aluminium with a benzene ring, i.e. 1,2- 1,3- and 1,4-addition. Calculations indicate that the most stable interaction is 1,4-addition, associated with a calculated binding energy of 7.4 kcal molq. This is in agreement with experimental observations.

A1

AI

A1

z ~ l H

H

1.350

Hd "

'N~H

,.....,H

H, ..... /~.453x..... ,H

H

1.4sl

.-,o,7 ,ii7 H

H

H

Bond lengths are given in Angs~oms Figure 5

Further calculations on the complex formed between alumim'um and benzene suggest there is little evidence for a stable AI ~-complex. The fine structure of the e.s.r, spectrum of the Al-benzene complex can be explained by the low distortion energy of the benzene boat structure which is enforced by bonding to the metal (S.J. Silva and J.D. Head, J. Amer. chem. Soc., 1992, 114, 6479). Theoretical studies have been undertaken on benzene complexes of univalent gallium salts (G.A. Bowmaker and H. Schmidbaur, Organometallics, 1990, 9,

127 1813). The model structures used in this study are shown in figure 6.

~+

Ki +

i I I !

I I ! I

<~>

<~>

l

,

"Ca*

a* ! !

i

J

' !

<(2)) C1 " ~ +.-CI..~Ga// ,

"CIj

\

Figure 6 Studies of the kinetics and the mechanism of aromatic thaUation (W. Lau and J.K. Kochu, J. Amer. chem. Soc., 1984, 106, 7100) show that both simultaneous electrophilic (two electron) and single electron transfer reactions

128 may occur. Three types of products are formed and these arise by either a) nuclear substitution, b) biaryl coupling, or c) side chain substitution (scheme 22). Ar-TI(O2CCF3)2 ArCH3 + TI(O2CCF3) 3

Ar-Ar -'- ArCH2.O2CCF3

Scheme 22 The preparation of arylthallium derivatives is also effected by reaction of thallium(Ill) chloride with arylsilver derivatives (A. Laguna et al., J. organomet. Chem., 1989, 365, 201).

5.

Group 4 Metals

5.1

Silicon and Germanium

The reaction of (LiSiMe3)6 (39) and its tertramethylenediamine adduct (LiSiMe3)2:(TMEDA) (40), with simple aromatic compounds has been examined (R. Balasubramanian and J.P. Oliver, J. organomet. Chem., 1980, 197, C7). Compound (39) reacts with benzene to give phenyllithium, however, in contrast (40) effects silylation as shown in scheme 23. Me3Si----Li (TMEDA complex) + LiH + TMEDA

Scheme 23

129 Both (39) and (40) metallate aromatic compounds beating acidic hydrogens, for example both afford benzyllithium upon reaction with toluene. Any difference in reactivity manifests itself only when the aromatic substrate does not have such an acidic site. Silicon containing cyclophanes have been prepared via the condensation of tris(2-thiophenyl)silane with 1,3,5-tris(bromomethyl)benzene (scheme 24) (R.A. Pascal, Jr. et al., J. Amer. chem. Sot., 1991, 113, 2672). The product has been characterised by proton n.m.r, and has a resonance at -1.04 ppm (Sill), compare this with a chemical shift of +6.13 ppm for the same resonance in an acyclic tris(alkyl)silane. The Si-H group exhibits a high-frequency stretching band in the i.r. spectrum of the cyclophane at 2457 cm "~, 280 cm"] above the acyclic model. Both spectroscopic features are due to the proximity of the Si-H group to the aromatic tings. X-ray crystallography reveals the structure of the cyclophane is as shown below, the distance between the apical silicon and the centre of the basal aromatic ring is only 3.34 A.

SLi

3~ L i

SH xc~

S Br

~H2Ph PhCH2~S~ X = Sill or P

Scheme24

S\CHePh

130 Silicon ions, Si§ form adducts with benzene and naphthalene molecues in the gas phase, this complexation significantly modifies the reactivity of the atomic silicon ion. Thus, significant differences are observed in the reaction of Si+ with D2, CO, N2, 02, H20, NH3, C2H2, and C4H2 in the presence of benzene and naphthalene and in the absence of these arenes (D.K. Bohme, S. Wlodek, and H. Wincel, J. Amer. chem. Soc., 1991, 113, 6396). There are also differences between the reaction of the two Si+-aromatic complexes. Reactions in the presence of benzene involve a n complex in which an atomic silicon ion is located above the benzene ring. Reactions in the presence of naphthalene, however, involve a neutral silicon atom sited above a charged aromatic surface. Theoretical and experimental studies have now provided evidence for the stability of the Si+-C6I~ n complex (H. Schwartz et al., J. Amer. chem. Soc., 1992, 114, 2802) The analysis of spectral characteristics and association constants of 1'1 complexes of phenyl derivatives of Si, Ge, Srg and Pb with tetracyanoethylene has revealed that there is little pn-d~ interaction and that the energies of the orbitals in the phenyl rings are unaffected by the size or electronegativites of the central atoms (J.E. Frey et al., J. Amer. chem. Sot., 1985, 107, 748). Electron diffraction studies ofp-bis(trimethylsilyl)benzene reveal that the two silicon atoms are nearly regularly tetrahedral but the benzene ring is considerably distorted 03. Rozsondai, B. Zelei, and I. Hargittai, J. mol. Structure, 1982, 95, 187). Phenylsiloxanes can be prepared by the reaction of benzene with pentamethyldisiloxanes (W.A. Gusstavson, P.S. Epstein, and M.D. Curtis, Organometallics, 1982, 1, 885). The reactions are eatalysed by Vaska's complex, (PPh3)(CO)IrCI, and is carried out under an atmosphere of nitrogen at 60~ The possible catalytic cycle is shown in scheme 25.

131

M-CI + RMe2SiH

~

M-H + Ph-H

--.,,t

"-

M-H

[M(H)(C1)SiMe2R]

+ RMe2SiCI

[MH2Ph ]

--- M - P h + H 2

"- M H

M - P h + RMe2SiH

.---

[M(H)(Ph)(S~VIe2R)] ~,,

Phil + RMe2SiH

~

H 2 + RMe2SiPh

+ PhSiMe2 R

Scheme 25

Hexamethylsilirane reacts with arenes, 1,3-dienes, conjugated acetylenes and benzyne with insertion of C=C or C~C into an Si-C bond of the silirane ring to give a silapentane or silacyclopentane (D. Seyforth et al., Organometallics, 1984, 3, 575). Scheme 26 shows how benzyne reacts with hexamethylsilirane via a two atom insertion. Side products due to Me2Si addition to the aromatic substrate are also formed, and at elevated temperatures the formation of these byproducts becomes competitive with the two atom insertion. For the two atom insertion reaction to be of synthetic use the reaction should be carried out with the addition of an inert diluent

Me

Me

Me Me~siMe2

Me

Me~- \ Me

M Scheme 26

Me

132 The photolysis of 1,4-bis(2-phenyltetramethyldisilanyl)benzene (41) in the presence of a large excess of isobutene in benzene yields (42), (43), and (44) in 49, 4, and 12% yields respectively (scheme 27). Irradiation over longer periods results in the formation of minor byproducts, less than 1%, the mass spectra of which (obtained by GC-mass spectrometry) corresponds to compounds (45), (46). and (47) (M. Ishikawa et al., J. organomet. Chem., 1992, 435, 249). Compounds (42) and (43) are formed by the rearrangement of (41), either a 1,3-dimethylphenylsilyl shift to the phenylene ring to yield (42) or a 1,3-shift of a dimethyl[(4-phenyltetramethyldisilanyl)phenyl]silyl group to an ortho carbon of a teminal phenyl ring to yield (43). These are primary photoproducts, compound (44) is not, but is formed by photolytic rearrangement of (43). This was confimed by isolating (43) and photolysing it, in a separate experiment, to give (44) in 9% yield.

~ /

~ SiMe2S i M e 2 - ~ ~

SiMe2---~O )

(45)

' SflVIe2H ~ (46)

SflVIe2H (47)

A series of pentacoordinate, anionic, arylsilyl complexes have been prepared in order to study the charge distribution in the aryl ring (K. Tamao, T. Hayashi, and Y. Ito, Organometallics, 1992, 11, 182). The anionic complexes are prepared by treating appropriate difluorosilanes

133

--~SiMe2SiMe2~SiMe2SiMe2~ (41)

I

.

.

.

.

.

.

.si~o~~_

so,~ s,~o~,so,~.,~

I CH2=CMe2

I

sosoocSs~ so,cc.o (43)

~

/

SiMe2CH2CHMe 2 (42)

.SilVle2

Me2Si~SiMe,2CH2CHMe2

SiMe2

Me2CHCH2SIMe2--~ ~,~-SilVIe2CH2CHMe2 @silo! ,:44, Schetm27

134 with KF in toluene in the presence of 18-crown-6 (R Damrauer and S.E. Danahey, Organometallics, 1986, 5, 1490). The complexes used in the study are shown in figure 7.

m

F X

- - - ~ ~ i

....,,F ~' "~R Me

F K +. 18-crown-6

i.....,F F

K+. 18-crown-6

X = CF 3, CI, H, Me, OMe, NMe2 R= CH3, Ph

~

F

X = 2-Me, 3-Me, 2,6-Me2, 3,5-Me2, 2,4,6-Me 3 R = Ph, 4-MePh, 3,5-Me2Ph

Figure 7 All have been examined by X-ray crystallography, which confirms their trigonalbipyramidal structures. ~gF and ~3C n.m.r, studies provide information about the charge distribution and by comparing the chemical shifts of the carbon resonances in the phenyl tings of Ph2SiF2 and PhESiFf with those of benzene the weak electron-accepting properties of the -SiPhF2, and the electron releasing nature of the -SiPhFf groups are established. The observation of the electronic effects in these complexes should be useful in the elucidation of reaction mechanisms of Si-C bond cleavage reactions which involve pentacoordinate intermediates. Aryl bridged cations have been proposed as intermediates in the solvolysis of organosilicon iodides by methanol and water ((2. Eabom, K.L. Jones, and P.D. Lickiss, J. chem. Soc., Perkin 2, 1992, 489). Two processes compete in the

135 solvolysis of (48); an SN2 process involving direct displacement of the iodide by the solvent and an SN1 mechanism involving loss of iodide, aided by the yaryl group, in the rate determining step.

Me2S i ..... ,,SiMe2i ~,,SiMe2

SN 1

Si S1

_-\

Y

M~ Me Y

(48) This SN1 mechanism is favoured when the Y group is electron releasing, conversely if Y is electron withdrawing then the Sr~2mechanism is favoured. The SN1 process is analogous to an electrophilic aromatic substitution and shows excellent correlation with o constants derived by Hammet considerations. Trimethylsilyl groups can be used to control regiochemistry in metal-ammonia reductions of naphthalene (P.W. Rabodeau and G.L. Karrick, Tetrahedron Letters, 1987, 28, 2481). For example, 1-methylnaphthalene is reduced, under Birch Reduction conditions, to give (49); reduction occurs in the unsubstituted ring as expected when the substituent is an electron releasing group. If, however, the methylnaphthalene carries a trimethylsilyl substituent then the reduction product is (50); reduction has been directed to the trimethylsilyl substituted ring. The final step in the process is the removal of the trimethylsilyl group by KOH or tetrabutylammonium fluoride. Thus a 'misoriented Birch Reduction' has been achieved.

136 Me

Me

Me

R=H

Me

R = SiMe 3 R

R

(49)

(50)

Aryl-germanium bonds are cleaved by elemental fluorine and by electrophilic fluorinating agents to yield aryl fluorides (Scheme 28). This method has been used to selectively introduce fluorine-18 into aromatic molecules (H.H. Coeenen and S.M. Moerlein, J. fluorine Chem., 1987, 36, 63). Yields of arylfluorides are highest when the aromatic ring bears electron releasing substituents, as expected for an electrophilic substitution.

[18F]. F2 or

18

[18F] - CH3CO2F ,,

.

X

X

X = OMe, Me, H, F, Br, CF3, NO 2 M = S i , Ge, Sn Schetne 28

137 Continuous visible-light irradiation of the germanium containing porphyrin (51) results in the photoeleavage of one of the o bonded phenyl groups, to give a zwitterionie porphyrin (G.B. Maiya, J.-M. Barbe, and K.M. Kadish, Inorg Chem., 1989, 28, 2524). The prophyrin has been eharaeterised by u.v.visible, proton n.mr. and e.s.r, speetroseopies. Laser-flash photolysis studies reveal that it is the triplet state of (51) which is photoreaetive. In contrast compounds, in which one or both phenyl groups of (51) are replaced by ferroeenyl ligands, are stable to photodegredation. It is postulated that energy transfer from the porphyrin triplet state to the axially bound ferroeene is involved in the stabilisation of these compounds.

R

R' (51) R=R' =ph R = R' = CHzPh R = R' = F erroeene R = P h, R' = F errocene Photolysis of digermanes results in cleavage of the Ge-Ge bond to give two germyl radicals which can abstract chlorine from CC14 to give chlorogermanes (K. Mochida et al., Bull. chem. Soc. Jpn., 1991, 64, 1889).

138 Similar pairs of radicals are formed in the photolysis of aryl-substituted germanium catenates. For example, irradiation of PhMe2GeSiMe3 results in the formation of PhMeEGe" and Me3Si', both can abstract chlorine from CC14 to give the chlorogermane and chlorosilane respectively (K. Mochida, H. Kikkawa, and Y. Nakadaira, J. organomet. Chem., 1991, 412, 9). Trialkylgermanium chlorides react with alkali metals to give trialkylgermyl anions, which upon treatment with aryl halides give the corresponding aryltrialkylgermanes. The mechanisms of these reactions has been studied (K. Mochida and N. Matsushige, J. organomet. Chem., 1982, 229, 11) and reveal that in the case ofaryl iodides, bromides and fluorides a radical process occurs (scheme 29), whereas, aryl chlorides usually react by an aryne process (scheme 30). ArX + R 3Ge-

[ArX-" R3Ge" ]

,

ArGeR3

tAr'X" "CR31

7 Ar"

Ar"

SH

+

-~ ArSH

Scheme 29

"GeR3

~

JAr"X" "GeR31

139

Me

Me

Me

()

R3GeH +

R3C~" e

CI

C1

Me

Me

( R3c,e

GeR3 Scheme 30

5.2

Tin and Lead

The cleavage of aryl-tin bonds by mercury(II) salts follows second-order kinetics when carried out in alcoholic solvents (M.R. Sedaghat-Herati and P. Nahid, J. organomet. Chem., 1982, 239, 307). The order of reactivity for the mercury(II) salts is HgCI2 > HgI2 >> Hgls. Measurement of activation parameters, which are low, suggests that an initial ~-complex is formed between PhSnE h and the mercury salt. This is supported by the high values for activation parameters obtained for the reaction of EtaSn with mercury halides; here the formation of ~x-complexes is not possible.

140 Reaction of YC6H4SnEt3 with mercury salts in THF is also second order (M.R. Sedaghat-Herati and T. Sharifi, J. organomet. Chem., 1989, 363, 39). The rate determining step involves reaction of the n complex formed between the reactants; the rate is not sensitive to substituents in the aromatic ring. The solid state structures of organotin halides of the type R3SnX and R2SnX 2 (R = aryl, X = CI, Br) have been elucidated by solid state 1195n n.m.r. (R.K. Harris et al., Organometallics, 1988, 7, 388). Comparison of solid state and solution state ll9Sn n.m.r, reveals that no gross changes in co-ordination of the metal occur between solution and solid state structures. Aryltributylstannanes bearing electron withdrawing groups have been prepared by palladium catalysed reaction ofhexabutylditin with aryl iodides (M. Kosugi, T. Ohya, and T. Migita, Bull. chem. Soc. Jpn, 1983, 56, 3855).

Pd(PPh3)4 Bu3SnSnBu3

+

ArI

~

ArSnBu3

+

Bu3SnX

This route to arylstannanes provides an alternative to the reaction of an arylorganometallic with an organotin halide, a method which is unsuccessful when the aromatic ring bears a reactive substituent (e.g. NOz, -COR, CN). Cross coupling of aryl triflates with stannylcuprates is also catalysed by tetrakis(triphenylphosphine)palladium to give arylstannanes (W.D. Wulff et al., Tetrahedron Letters, 1988, 29, 4795)

141 OSO2CF3

SnBu3 Pd(Ph3P)4

+ 03u3Sn)2Ct~NLi

H

'~CF3CO2 H

Neighbouring tertiary amine groups bonded to arylstannanes increase the rate by which these catalyse the palladium mediated arylation of furoyl chloride (scheme 31) (J. Brown et al., Chem. Comm., 1992, 1440).

Sn reagent Ph O

Ph3P\ /El ph Pq

Feb3 O Scheme 31

O

142 Furoyl chloride does not react appreciably with Ph3SnMe at 40~ but if compound (52) is used as the tin substrate the reaction shown in scheme 31 goes to completion in 30h at 20~ Thus, the amino substituent is involved in the key transmetallation step.

(52) Rate constants for the abstraction of bromine atoms by tributyltin radicals from a series of aryl bromides (D.P. Curran et al., J. org. Chem., 1991, 56, 7162) show that electronegative substituents on the arorhatic ring increase the rate of bromine abstraction. These measurements can be used in planning synthetic procedures where more than one radical precursor is present. Reaction of tetraarylstannanes or triphenyltin halides with diborane results in the transfer of one or more aryl groups from tin to boron. These arylboron intermediates yield phenols upon oxidation and boronic and borinic acids when hydrolysed (F.G. Thorpe et al., J. organomet. Chem., 1994, 62__~,7). The transfer of aryl groups is a stepwise process. Scheme 32 shows the possible sequence of reactions for tetraaryl stannanes.

Ar4Sn

+

BH 3

~

Ar3SnH

+

BH 3

,~

Ar2BH

+

Ar2SnH2

Ar4Sn

+

ArBH2

~- Ar2BH

+

Ar3SnH

Scheme 32

ArBH2

+

Ar3SnH

143 The presence of A r B H 2 is suggested by the formation ofboronic acids upon hydrolysis and the formation of borinic acids suggests Ar2BH is formed. The sequence of reaction for triaryltin halides is shown in scheme 33.

Ar3Sn

+

BH3

~

Ar3SnH

+

XBH2

Ar3Sn H

+

BH3

~

Ar2SnH2

+

ArBH2

Ar3SnH

+

XBH2

.~

Ar2SnH2

+

ArBHX

Scheme 33 The nature of X determines the reaction pathway, but the formation ArBH2 explains why monoarylboron species are observed aider hydrolysis in the presence of excess diborane. When stoichiometric quantities of diborane are used XBH2 becomes the dominant species formed. Structure (53) is believed to be the important reaction intermediate in the aryl transfer process.

Ar3S

1-13

(53)

144 Selective mono-fluorination of aromatic substrates can be achieved by ipsosubstitution oftrialkytin groups. The fluorination proceeds v i a an electrophilic substitution pathway and can be effected by elemental fluorine, caesium fluoroxysulphate (M.R. Bryce, R.D. Chambers, S.T. Mullins and A. Parkin, Bull. Soc. chim. France, 1986, 1624), or by trifluoromethyl hypofluorite (M.R. Bryce, R.D.Chambers, S.T. Mullins, and A. Parkin, J. fluorine. Chem., 1984, 26, 533). This methodology has been developed in order to selectively fluorinate imidazole derivatives

/~N~M Me3Sn~

e

F2/N2~

~ Me

/~N~M

e

F~}~ Me

Arylboronic acids undergo rapid boron-lead exchange with lead tetraacetate in the presence of catalytic quantities of mercury(II) acetate (J. Morgan and J.T. Pinhey, J. chem. Soc., Perkin I, 1990, 715). Hg(OAc)2 PhB(OH)2 + Pb(OAc)4

PhPb(OAc)3

This reaction has been developed as a convenient method for 'in situ' preparation of useful electrophilic C-arylating agents for ketones.

145 O ArB(OH)2 O2Et

i) Pb(OAc)4, Hg(OAc)2, CHC13 ii) 2- Ett~xycarbonylcyclopentanone

A series of tetraaryllead compounds have been studied by electron impact and fast atom bombardment mass spectrometry (M. Gielen, H.O. Van der Kooi, and J. Wolters, Main Group Metal Chemistry, 1987, 1_.0, 1).

6.

Group 5 metals

A series of arsenic compounds of general structure (54) have been prepared by the condensation of benzaldehydes, pyruvie acid, and p-arsanilir acid. Investigation of their antimicrobial activity shows them to be very effective against Staphyllococcus aureus, but not particulary potent against Escherichia coli (D.J. Bhatt, G.C. Kamdar, and A.R. Parikh, J. Inst. Chem., 1984, 56, 233).

~

C.O2H

H

o-- I OH

R (54)

146 The reaction of benzene with arsenic pentafluoride results in diphenylfluoroarsonium hexafluoroarsenate which reacts with CsF to give PhEAsF3 and C s A s F 6. 19F n.m.r, studies reveal that Ph2AsF3 is trigonal bipyramidal with the phenyl groups in equatorial positions (F.L. Tanzella and N. Bartlett, Anorg. Chem. org. Chem., 1981, 36B, 1461). Arsabenzene (55) is aromatic; it undergoes electrophilic substitution at the 2and 4-positions. For example, Friedel-Crafis acetylation results in a mixture of 2- and 4-acetylated products, nitration also gives a mixture of 2- and 4substituted products (A.J. Asche III. et al., J. org. Chem., 1981, 46, 881).

COMe +

~.COMe

+ CH3COC

(55)

Treating SbC13with naphthalene, anthracene or phenanthacene results in the formation of adducts of the general formula SbCI3.Ar (where Ar is the aromatic substrate). Further treatment of the adducts with cyclopentadienyl, or indenylsodium (RNa), then results in RESbCI3.Ar (R.C. Sharma and M.K Rastogi, Curr. Sci., 1983, 5_22,862). The non-benzenoid aromatic, lithium 2,5-dimethylstibacyclopentadienide (56) has been prepared as shown in scheme 34. This compound reacts with metals to give analogues (for example 57 and 58), of more familiar cyclopentadienyl complexes.

147 c~ R2Snn2

R

CCH3

R

I PhSbCl Li

I Li

I Ph

(56)

.,~CO) 5

FeCl2~

.CH3

i ~ Sb [ cH~

Mn(CO)3

b H3c

(57)

Fe

H3c

(58)

Scheme34

148 Cyclopentadienyl complexes containing bismuth have also been prepared (scheme 35) (A.J. Asche HI and J.W. Kampf, J. Amer. chem. Soc., 1992, !14, 372). Again, analogous compounds to ferrocene can be prepared using this new heterocycle in combination with Fe(II) salts.

Me3Si

\

SiMe 3

Me

/

i

i \ I

"

i)

i--Ph

SiMe 3

~--

~Li

"

Me" SiMe3

\

Me" SIMe3

\ SiMe 3

i) = BuLi ii) = PhBiI2 Scheme 35

Sterically crowded arylbismuth complexes are prepared by the reaction of BiC13 with 2,4,6-tris(trifluoromethyl)phenyllithium in ethereal solution. The products (1L,)2BiC1and (Rr)3Bi are monomeric in solution and in the solid state and whereas (Rr)2BiC1is relatively stable (Rf)3Bi is not, even in solution under an inert atmosphere (K.H. Whitmire et al., J. organomet. Chem., 1991,402,

55). The aryl groups in pentavalent bismuth organometallic complexes may migrate from bismuth to carbon. The rates of migration vary according to the substituents on the aryl ring, but the mechanism involved appears to be one of reductive elimination, without the generation of discrete ions or radicals (D.H.R. Barton, N.Y. Bhatnagar, J.-P. Finet, and W.B. Motherwell, Tetrahedron, 1986, 42, 3111).

149 7

Group 6 Metals

The organic chemistry of selenium and tellurium has been reviewed in two volumes of'The Chemistry of Functional Groups' (The Chemistry of Organic Selenium and Tellurium Compounds Vols 1 and 2, Ed, S. Patai, John Wiley, 1987, Chichester). A more recent text dealing with the organic chemistry of tellurium was published in 1994 (N. Petragnani, Tellurium in Organic Synthesis, Academic Press, 1994, London). Aromatic tellurides and ditellurides are receiving increasing attention as starting materials for the preparation of organic conductors and imaging systems, they are also useful as synthetic reagents. An efficient synthesis involves reaction of sodium telluride, from metallic tellurium and sodium hydride, with nonactivated aryl iodides (H. Suzuki and T. Nakamura, Synthesis, 1992, 549). Aryltellurides are also readily prepared by the action of tellurium tetrachloride with trivalent organometallic compounds of boron and aluminium. Aryl groups are transferred from the group 13 metal to tellurium (D.P. Rainville and R.A. Zingaro, J. organomet. Chem., 1980, 190, 277). Treatment of the teUuronium salt (59) with an organolithium, followed by addition of an aldehyde results in the formation of secondary alcohols (L.-L. Shi, Z.-L. Zhou, and Y.-Z. Huang, J. chem. Sot., Perkin I, 1990, 2847). The reaction (scheme 36) involves alkylation of (59) to give an unstable tetraorganotellurium, which undergoes nucleophilic addition to the aldehyde to produce the secondary alcohol (60).

150 OH R'Li

RCHO

!

RCHPh + (telluroniumhydroxide)

Ph2(Me)Te+BP1M-

H2o (59)

(60)

R= Ph, p-CIC6H4, p-BrC6H4, p-FC6H4, p-MeC6H4, p-MeOC6H4, 2-naphthyl, 2-pyridyl R' =

Me, Bu, Bu t, Ph Scheme 36

Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds, Vol.Ill B, C,D(Partial), edited by M. Sainsbury

151

9 1995 Elsevier Science B.V. All rights reserved.

Chapter 11 AROMATIC COMPOUNDS OF THE TRANSITION ELEMENTS A. J. PEARSON and P. D. WOODGATE 1. Introduction The preparation, structural characterization and properties of aromatictransition metal organometallics was treated in detail by M. A. Bennett in Volume IIIB, Chapter 11 of this Series, and the literature to around 1974 was covered therein. Much of the research on this area of chemistry during the last two decades has been directed towards applications in organic synthesis, and in materials chemistry, so these two themes will be focused upon in the present chapter. Advances in our understanding of the chemistry of organometallic complexes often occur alongside efforts to apply them in synthesis, which justifies this focus at the present time. Those readers who wish to acquire information on structure, spectroscopic properties, etc., are referred to Bennett's earlier review, as well as the references cited in the present chapter. The main advances that have taken place over the last ten years have been in the chemistry of arene-metal n:-complexes of the chromium, iron and manganese groups. Accordingly, the discussion will focus heavily on these metals. Also, while there have been many noteworthy advances in the use of the Heck reaction, involving the catalytic generation of aryl-palladium ~-complexes, these are considered to be outside the scope of this chapter and are not discussed (for reviews, see: A. D. Ryabov, Synthesis, 1985, 233-252; R. F. Heck, "Palladium Reagents in Organic Synthesis", Academic Press, New York, I985). A transition metal that is rt-complexed to an aromatic ring can mediate a wide variety of transformations, which are summarized diagrammatically in Figure 1. Not all metals allow the exploitation of all of these reactivity phenomena. For example, while the [Mn(CO)3] + group is the most activating with regard to nucleophile attack on an attached arene ligand, it does not effectively promote many of the other reactivity patterns shown in Figure 1, owing in part to its sensitivity toward reagents and reaction

152 conditions that are employed for such processes. The Cr(CO)3 group, on the other hand, being the least activating, shows the full range of chemistry shown in Figure 1. The activating power toward nucleophile additions has been reported to follow the order: Cr(CO)3 < Mo(CO)3 <<[ FeCp] + < [Mn(CO)3] +. For a given metal the reactivity of haloarene complexes toward nucleophilic substitution is" fluorobenzene > chlorobenzene > chlorotoluene (A. C. Knipe, S. McGuinness, and W. E. Watts, J. Chem. Soc., Perkin Trans. 2, 1981, 193). Figure 1" GeneralReactivityPatternsof Arene-Metal~-Complexes Reactions ai M and

MLn

L

Metallatlon ~ .~ . (deprotonation)r''~" H~ ' - ' ~ ~ = ~ b X Nucleophile ~ _ . . / \_v oNfUhC~OPidehsilcdisplacement addition to ring / H 2 C~ Stabilizationo! benzylic catbocations(SN1)

Stabilizationof benzylic carbanions(deprotonation)

STEREOCONTROL: ML n blocks syn face of complex, leading to nuc/eophile addition anti to metal.

2. Manganese, Technetium and Rhenium

2.1 176 Complexes The hexahapto arene complexes of manganese are extremely reactive toward nucleophiles, and offer some advantages over the analogous chromium derivatives, since a wider range of nucleophiles (less reactive) can be employed in various bond-fomaing reactions. Unfortunately, the rather harsh conditions that are nomaally used for their preparation [Mn(CO)sBr/A1CI3/ heat] preclude the use of aromatic compounds having sensitive functional groups. It has been shown that pentacarbon~,lmanganese perchlorate reacts with arenes to deliver the corresponding 1"1~ complexes, this method even allowing the preparation of the extremely moisture-sensitive fluorobenzene complex (K. K. Bhasin, W. G. Balkeen, and P. A. Pauson, J. Organomet. Chem., 1981, 204, C25). A similar method involving the use of pentacarbonylmanganese tetrafluoroborate under mild conditions (CH2C12, reflux) allows the preparation of rl6-veratrolemanganesetricarbonyl tetrafluoroborate (A. J. Pearson and I. C. Richards, J. Organomet. Chem., 1983, 258, C41) which reacts with enolate nucleophiles regiospecifically as shown in Equation 1. OLi

9

OMe

OMe [Mn(CO)s][BF4] CH2CI2,A 66%

q,~.)~Mn(CO)3 PFs"

~

O

M

e

O " ~-"'Mn(CO)3

(1)

153 The above methods of complexation, however, do not work universally, there being a number of arenes that either give poor yields or no complex at all. In such cases the method reported by Rybinskaya et al., involving treatment of the arene with Mn(CO)5C1, or Mn2(CO)8C12 in the presence of 48% aqueous HBF4 in trifluoroacetic anhydride at reflux temperature, is often a useful alternative (M. I. Rybinskaya, V. S. Kaganovich, and A. R. Kudinov, Bull. Acad. Sci. USSR, Div. Chem. Sci., 1984, 33, 813). It is noteworthy that air need not be excluded during this reaction, though of course the method is limited to acid stable aromatics. The reactions of arene-Mn(CO)3 cations with nucleophiles have been studied fairly extensively by S weigart and co-workers. Particularly interesting is the capability of the manganese group to allow sequential nucleophile additions in a stereocontrolled manner, ultimately allowing the conversion of aromatic molecules to stereodefined cyclohexadienes and cyclohexenones. This aspect of the chemistry of arene-manganese complexes has been reviewed recently, and a brief overview will be given here (R. D. Pike and D. A. Sweigart, Synlett, 1990, 565). Reaction of the benzene-Mn(CO)3 cation with Grignard reagents proceeds stereospecifically anti to the metal, as established by X-ray crystallography of a phenyl adduct (S. D. lttel et al., Organometallics, 1988, 7, 1323; Eq. 2). While the product dienyl complex itself is not very reactive toward nucleophiles (but see later), displacement of one CO ligand by NO + occurs easily, giving the electrophilic dienyl-Mn(CO)2NO cation. The latter complex reacts stereospecifically, again anti to the metal, with all nucleophiles except borohydride, which adds syn (Y. K. Chung et al., J. Am. Chem. Soc., 1982, 104, 4245; ibid., 1985, 107, 2388). +

~--IV~n(CO)3

RMgX ---

pF6-

NOPF6 Mn(CO)2N O Mn(CO)3 CH2CI2, 25 ~ 15min O PF6

~ : R

ca100% NaBD,1,T H F , f

Mn(CO)2NO

(2)

: R /

~

P(OMe)3

Mn(CO)2NO

Mn(CO)(NO)P(OMe)3 PFe

D

. R 9.

R'3

: R R"= Ph, n-Bu ~

R

The syn mode of hydride delivery from borohydride was confirmed by Xray structure determination of the diene complex that results from double nuc]eophile addition to the 4-methylaniso]e complex (Y. K. Chung et al., Organometal]ics, 1983, 2, 1479; Eq. 3). It should be observed that the poor regiose]ectivity during borohydride addition to the pheny]-substituted dienyl

154

complex shown here is probably the result of combined steric hindrance, and much better selectivity in favor of attack at the methyl-substituted terminus is anticipated for complexes lacking exo substituents. Mn(CO)3 NOPFe C H2CI,2

Me0 Ph~~"r

" ~ "Me

e~

calO0*/*

+

Mn(CO)~lO PFe"

V ' =PhM e

100% + I~/~"-Mn(CO)3 ~Me pF6-

MeO~

(3)

I NaBI-~,THF, MeOH 89*/. Me O ~ f ~ O)2N0 Iv. "Me Ph

Me O , ~ ~ n(CO)2N0 +

.v! Me Ph

1.5:1

The mechanism of e n d o hydride addition has been investigated for dienylM(CO)2NO complexes (M= Mn and Re), and is proposed to occur via addition to a CO ligand, followed either by direct transfer to the dienyl ligand or by deinsertion followed by a reductive elimination (R. D. Pike et al., J. Am. Chem. Soc., 1990, 112, 4798; Eq. 4). H. o

~n(CO)2N0

H'~ Mn(CO)NO "

:. R

: ~

O0

"~~nsfer ~

0 J

Mn(COJ2NO

reduclive

(4)

elimination

Mn(CO)2N0

R

Various nucleophiles have been studied as partners in these addition reactions. Thiophenoxide adds predominantly to the arene ligand, but small amounts are formed of the complex resulting from addition to CO; if thiophenol is used in the presence of trimethylamine N-oxide, which effects removal of a CO ligand, the product of CO ligand replacement is obtained. The same product is isolated from reaction of arene-Mn(CO)2(THF) complexes with thiophenol (M. Schindehutte, P. H. van Rooyen, and S. Lotz, Organometallics, 1990, 9, 293; Eq. 5). Several reactions of arenemanganese complexes with lithiated cyano-imines, as well as nitronates, have been reported (F. Rose-Munch and K. Aniss, Tetrahedron Lett., 1990, 31, 6351; Eq. 6, 7).

155 R

R~.,Mn(CO)3

PhSNa

IC')i v

pF 6-

~"~h

SPh

R = H, 1,3,5-Me3, or Mes

R

R

+

Mn(CO)2COSPh

minor

(5)

l hv, or Me 3NO,PhSH, TH F 65%

~'N~ I ~ - - - ' - - - Mn(CO)2SPh

HPF,

R~'X"~"I I~~M

=

+n

P (CO)2(HS h) PFe"

Mn(CO) 3

R LiC(Y)(Z)N=C ph2 Mn(CO)3 R

R~R (6)

61 - 86% except R = Me(c)(12%)

PF6

C(Y)(Z)N=CPhz

R = H or Me; (a) Y = CN, Z = H; (b) Y = CO2Me, Z = H (c) Y = CO2Me, Z = Me Mn(CO)3 a

~"~--" '4"~C

Mn(CO)3

LiCH(R')NO 2

+

Mn(CO)3 I pFe-

(7)

9

80 - 91%

-

CI

R

CHR'NO 2

R = H or Me

CHR'NO 2

R = H: 75:25; R = Me: 84:16

It has been found that chiral-at-metal dienyl-Mn complexes react diastereoselectively with carbon nucleophiles, such as stabilized enolates, e.g., dimethyl malonate anion (R. D. Pike et al., J. Am. Chem. Soc., 1989, 111, 8535; Eq. 8). While this behavior holds some promise for asymmetric synthesis, it suffers from the drawback that the chiral complexes would have to be optically resolved in order to produce non-racemic compounds. §

Mn(CO)(NO)PMe3

@

/Mn(CO)(NO) PMe3

NaCH(CO2Me)2O

: R

R

(8) "C H(CO21Vle)2

The arene ]igand acts as a spectator during nuc]eophile additions to dicarbonyl(alkene)(arene)manganese cations, which occur chemoselectively at the alkene ligand (W. A. Halpin et al., J. Am. Chem. Soc., 1989, I l l ,

376; Eq. 9).

O__ §

Mn(CO)3 pF6"

M e3N O

THF O__M+ n

--80 - 90%

alkene

PF6"

CH2CI20--f

(CO) 2(THF) ,, = pF 6. >80%

n(CO)2

R/~NR other arenes: C6Me6; C6H3Me3; C6HMe 5

alkene = propene; cyciopentene; norbornadiene; dihydroturan; ethyne

156

Nudeophile

O ~ ~

R--(

n(CO)2

(9)

R

X X = [PF:~*" H; CN

Analogous reactions of arene-Re(CO)3 complexes with nucleophiles, followed by activation and second nucleophile addition, have been reported, though rhenium is likely to be a less useful stoichiometric arene activator than manganese (R. D. Pike et al., Organometallics, 1989, 8, 2631; Eq. 10).

,~

R

I)de=r~, Re(CO)'r'AIC'3' ~ ~so ~ ~h 2) NH4PFs m. 71%

R=H:~~.Re(CO)3

R'~(CO)~ R'MQXPF 6" R

H

R = H or Me

NOPF6

pF6-

,,,. H R'

R'

R'= Ph (70%)

NaBH4, MeCN, ,~ THF, -5 oC

~L~;Re(CO)2NO

I

(lO)

M ,

H

R~

R'= Ph (17%) R'= Me (62%)

Reaction of NaP(O)(OR)2 with benzene-Mn(CO)3 leads to a dienyldialkylphosphonate which can be deprotonated with BuLi. Treatment of the anion with water leads to the endo phosphonate complex, but the reaction with BuLi is accompanied by some nucleophilic displacement of the phosphonite (H. K. Bae, I. N. Jung, and Y. K. Chung, J. Organomet. Chem., 1986, 317, C1; Eq. 11).

O_ +

NaP(O)(OR)2

Mn(CO)3

Mn(CO) 3

I)n'BuLi~__~

THF 0 Mn(CO)3 R = Me or El .-2) H20 P(O)(OR)2

+

O

Mn(CO) 3

P(O)(OR)2

Bu

65%

14%

(11)

A reversal of regioselectivity during the addition of Grignard reagents to substituted arene complexes has been observed. While vinyl-MgX reagents add to the less hindered position, methylmagnesium bromide adds predominantly to the more hindered position, but no explanation of this phenomenon was offered (R. P. Alexander and G. R. Stephenson, J. Organomet. Chem., 1986, 314, C73; Eq. 12). Conversion of the dienylMn(CO)3 complexes to cationic dienyl-Mn(CO)2NO systems was achieved but no reactions of these complexes with nucleophiles were reported.

157

Me MeO,,,,~ + I~ ~ - ' - - M n(CO)3 ~ M e

MeO

RMgBr =

~ M e Mn(CO) 3 MeO M y ~ , , , R " ~ ..._ +

pF 6-

: R

Me

e Mn(CO)3

R = CH=CH2; 4:1 (75%) R = CH=CHMe; 9:1 (unstable) R = Me; 1:4 (unstable)

R = CH=CH2,

M e

+ Mn(CO)2NO major product: NOPF6 MeO " ~ ( ~ L pF 6V.

(12)

Me

CH=CH 2 50% overall from arene-Mn(CO)3 complex

The reaction of benzene-Mn(CO)3 with phosphorus ylides results in the formation of substituted phosphonium derivatives which can be converted to alkenes in the presence of the dienyl-manganese group, using standard Wittig reaction conditions (S. Lee, Y. K. Chung, T-S Yoon, and W. Shin, Organometallics, 1993, 12, 2873; Eq. 13). Mn(CO)3 C - -

+ Ph3P=CHR d Mn(CO)3 = PF6" R = H (86%) : + R = Me (45%) CHRPPh3 R = OMe (63%) R = Et (60%)

Mn(CO) 3 1) LDA 2) R'CHO

O

42 - 66%

(13) .-" CR=CHR'

R'= Me, Ph, Et, p-CsH4OMe

PF6"

R = OCH2Ph (38%)

Treatment of arene-Mn complexes with sodium halides results in the formation of arene-Mn(CO)2X complexes, from which the halide can be displaced by hydride nucleophile. In some cases better yields are obtained when the halide addition is carried out in the presence of Me3NO; similar behavior is found for arene-rhenium complexes (R. J. Bernhardt and D. P. Eyman, Organometallics, 1984, 3, 1445; R. J. Bernhardt et al., Organometallies, 1986, 5, 883; Eq. 14 - 16). X=I

NaBH 4 80% =

hv, 3 - 5h

[(Arene)Mn(CO)3] § + NaX

= (Arene)Mn(CO)2X

Mn(CO)2H

(14)

Arene = C6Me6: X = I (76%); Br (64%); CI (19%) Arene = C 6H 3M e3, X = I

I R: 1940, 1890 cm'l; 1H NMR: ~ -10.9 for Mn-l-l. [(Arene)Mn(CO)3]*

+ Bu4NX

Me3NO ~ (Arene)Mn(CO)2X

(15)

Arene = C sMe6: X = I (80%); Br (79%); CI (23%) Arene = C sH3Me 3, X = 1(40%); Arene = 06H6, X = I (70%)" Arene = C 6HsM e, X = I (40%)

NaCN, MeOH, z~

MeLi,-78 ~

( C 6M e6) M n ( C O)2M e --

(C 6M e6) M n (C O)2Br

100%

(C sM e6) Mn(CO)2C N

(16)

158 As mentioned earlier the neutral dienyl-Mn(CO)3 complexes that result from nucleophile additions to the arene ring are rather unreactive towards most of the conventional nucleophiles used in this area of chemistry. Brookhart discovered that, while reaction of arene-Mn(CO)3 complexes with one equivalent of triisopropoxyborohydride or triethylborohydride leads to the expected dienyl complex, reaction with two equivalents of the hydride source affords diene-Mn(CO)3 anions (M. Brookhart and A. Lukacs, Organometallics, 1983, 2, 649; M. Brookhart, W. Lamana, and A. R. Pinhas, ibid., 1983, 2, 638). Reaction of these anions with water leads to the formation of the hydrogen bridged (so-called a g o s t i c ) c o m p l e x e s . Alternatively, treatment of the anions with oxygen effects their conversion to neutral diene complexes which can be demetalated to give the free dienes (M. Brookhart and A. Lukacs, J. Am. Chem. Soc., 1984, 106, 4161). These observations are summarized in the following equations. Other electrophiles, e.g., alkyl halides, can be used to effect alkylation, etc., of the anions.

~

[BH(OP?)3 ]

R.

1equiv

~Mn(CO) 3 Me R = H or Me

~

--

Mn(CO)3

R

Me R = H, 40:60 R = Me, 65:35

Me ,~~/_~_..._M3n§(CO) " ~ " ' ~ Me

Mn(CO)3

(17)

Mn(CO)a

[BH(OPr') 3]"

1 equiv

Me +

Me~M

(18)

e

2 equiv

Q

, [BH(OPri)3] Mn(CO)3 or Et3BH" S ~~}

~ /

I H20

1) KH 2) 0 2

~__~V~O

.H, )3 ~

O.~M

n(CO)3

(19)

Based on Brookhart's results, McDaniel and co-workers have reported the addition of reactive carbon nucleophiles to the neutral dienyl complexes to give, after oxidation, stereodefined disubstituted cyclohexadienes (X = CHPh2, 2-(1,3-dithianyl), C(Me)zCN, CPh3, C(Me)2CO2Et; B. C. Roell, Jr., et al., Organometallics, 1993, 12, 224; Eq. 20). Similarly, Sheridan et al. have shown that very reactive nucleophiles such as MeLi or PhLi react with neutral cyclohexadienyl-Mn(CO)3 complexes initially at a carbonyl ligand to give an acylmetalate. Treatment with acid (HBF4.OEt2) induces transfer of the alkyl group from CO to the endo face of the n-complex to give a mixture of agostic cyclohexenyl complexes which can be decomplexed

159 either using Brookhart's two-step KH/O2 sequence, or non-oxidatively using dppe to precipitate lHMn(CO)3(dppe)] (H. B. Sheridan et al. J. Chem. Soc., Dalton Trans., 1992, 1539; Eq. 21). Mn(CO)3

o Mn(CO)

F

x-.'"'.""Ix .o',] o..o -78 ~ to rt

.= R

,,"

(20)

X""

: R 43 - 91% overall X as in lext

| Mn(CO)3

n(CO)2CO

R2Li, Et20,d ..R1

1) HBF4

L

: Iu

2) 0 2 o r dppe

(21) -

FF

R'

R = H, Me, or p-tolyl

Addition of nucleophiles to anisole-Mn(CO)3 derivatives proceeds with good regioselectivity, favoring attack at the meta carbon, and the product dienyl complex can be converted to 5-substituted cyclohexenones. This reaction also creates a stereogenic center, but produces a racemic mixture. The application of this chemistry to organic synthesis would be more attractive if asymmetric induction could be achieved during the nucleophile addition step. Miles et al. have investigated the reactions of alkoxy substituted arene complexes with chiral enolates, using Evans' chiral auxiliaries, and have obtained reasonable levels of asymmetric induction. Conversion of the dienyl complexes to 2-arylpropionate esters, via oxidative demetalation, eliminates the ligand asymmetry and gives the products in high yield and high enantiomeric excess (W. H. Miles, P. M. Smiley, and H. R. Brinkman, J. Chem. Soc., Chem. Commun., 1989, 1897; W. H. Miles and H. R. Brinkman, Tetrahedron Lett., 1992, 33, 589; Eq. 22. For related chiral enolate additions to dienyliron and dienemolybdenum complexes, see: A. J. Pearson and J. Yoon, J. Chem. Soc., Chem. Commun. 1986, 1467; A. J. Pearson, S. L. Blystone and B. A. Roden, Tetrahedron Lett. 1987, 28, 2459). High levels of asymmetric induction have been observed during the addition of a number of hydride and carbon nucleophiles to arene complexes having a C2 symmetric dimethylpyrrolidine directing group; however, methods for the conversion of the product dienyl complexes to cyclohexenones have not yet been reported (A. J. Pearson et al., J. Am. Chem. Soc., 1993, 115, 10376; Eq. 23).

160

al

O

+

"~~m "~R

Mn(CO)3

Mn(CO)3 2 BF4 or PF6"

Me

(:a75% yield;>9:1 d.e. torR1= FI2=H 1) DDQ, LiOCH2Ph \ \ \ R1= H, R20Ph 2) MeCN,, ~ / = 6% ~ several steps H 2, Pd-C, ~ O EtOAc, EtOH RL j ~ L " COAr (22) 87% O'~O R2 CH2Ph H Me

a1

CI ~~

R1

Me,,.,, ~ . Me....~ . , M e Amine,2.5 equiv. N Me Mn(CO)3+ K2C~O3' 1 - 1CH2Cl2' 2h 1 ,~ ~ I V n(CO)3 PhMgBr' n ( C~OTHF ) 3 - 7 8~ . , M PF6"

87%

PF6

72%

(23)

Ph 95:5 d.e.

Reactions of a number of nucleophiles with chloroarene-Mn(CO)3 complexes leads to displacement of the halide. Since the Mn(CO)3 group is very easily removed from the arene ligand by treatment with acetonitrile at room temperature, this provides an exceptionally mild method for effecting nucleophilic aromatic substitution. Pauson showed in 1975 that even phenoxide nucleophiles will displace chloride at 0 ~ allowing construction of diaryl ethers (P. L. Pauson and J. A. Segal, J. Chem. Soc., Dalton Trans., 1975, 1677). A number of important natural products, such as vancomycin and related compounds, have a diaryl ether as a key structural feature, but the presence of sensitive peptide functionality in the molecule precludes the use of harsh reaction conditions for setting in place the ether bond (e.g., Ullmann coupling). Chloroarene-manganese complexes appear ideally suited to this kind of synthesis problem, and a number of publications have appeared delineating their application. For example, early work showed that aryl ethers could be prepared, without racemization, by the reaction of chlorobenzene-Mn(CO)3 with the phenoxides from protected tyrosine as well as hydroxyphenylglycine derivatives (A. J. Pearson, P. R. Bruhn and S.

Y. Hsu, J. Org. Chem., 1986, 51, 2137; Eq 24).

161 THF, MeCN + 0oC,30min ~ O Mn(CO)3 ,PF6" R R = CH2CH(NHAc)CO2Me (76%) R = CH(NHAc)CO2Me (75%)

...~ONa+C,~ R

~

~

+ Mn(CO)3 PF6"

/

/ MeCN, rt

(24) 55 - 65% overall yield

Coupled with nucleophile addition of chiral glycine enolate equivalents to arene-Mn(CO)3 complexes that result from the ether-forming reaction, this chemistry allows the preparation of diaryl ethers in which both aromatic rings carry an amino acid substituent (A. J. Pearson, P. R. Bruhn, F. Gouzoules and S. H. Lee, J. Chem. Soc., Chem. Commun., 1989, 659; A. J. Pearson and P. R. Bruhn, J. Org. Chem., 1991, 56, 7092). These studies have culminated in the synthesis of a 14-membered cyclic peptide/aryl ether which serves as a model for the construction of part of the ristocetin A structure, as outlined in the following scheme (A. J. Pearson, S. H. Lee, and F. Gouzoules, J. Chem. Soc., Perkin Trans.1, 1990, 2251; A. J. Pearson and H. Shin, Tetrahedron, 1992, 48, 7527; A. J. Pearson and H. Shin, J. Org.

Chem., 1994, 59, 2314). OH M

.

Nail, THF, 0 "C, 0.5h, then AgBF4 complex A, 0 "C, 45 min.; NH4PF6 70% =,

MEMO~~N,~NHBo c PFs" MeO~~~O ~

+

(CO)31~n""~l

Mn(CO)3 OMe

BF4

MeO

,O,M E ~ N ~ N H B o c

N:"~ ~ 1) MEOW.. N

I 2) NBS, Et20, rt, 15 rain. I 45 - 50% yield THF,-100 to-9Li5"C, 25 min.1

1) 0.25N HCI, THF 2) PhCH2OCOCI,etc. 90%

Me

OMe

Me

CI Me (A)

H

MeO~ MeO

OMe

Me

H((z):H(~) ratio = 15:4

162 OR' RO, 2) E ~MgBra.EIaO, d'cl' Et20,rt H H 3) MeO2C

. . ~ H NHBoc

HN~

M.

OH

~ H N ~ . o -'HH., ~ N

O

f~ T Io. HOA~,,,,'%OR."""

oM.

~o. " ~I ~ 1 ~

o

+ N H N'~H NH3 HN ~ .,,~.,, O H ~ O H ~

RISTOCETIN

.o- y

~o~ Me

A

y

OH

(R. R' and R"= sugar units)

Benzylic hydrogens are rendered acidic by the neighboring arenemanganese system, as expected. Deprotonation of hexamethylbenzeneMn(CO)3, followed by reaction of the intermediate methylene/dienyl complex with electrophiles provides a new method for functionalization of benzylic positions analogous to the well-known arene-chromium chemistry. The intermediate methylene compound shown below has been characterized by X-ray crystallography (D. M. LaBrush et al., Organometallics, 1991, 10, 1026). ~ MI

~ n(CO)3 PFe"

KHT ,HFrt, . 8h ~

(CO)3CHBr3 ~C~B+

~Mn(CO)3

77%

NI-14PF6 ~ooo/o

c 89

r2

(52%)

,

Ioc,. ) DC

~ + " 2)NH4PF6 : .~.T_____ Mn(CO)3 ,,,y~ LCOPh P F 6 "

o

~Mn(CO)3

+

~r~,Mn(CO~ L

12

"COl3

2.2 172 Complexes

Treatment of 111-aryl-Re(CO)(NO)Cp com.plexes (Cp = rl5-cyclopentadien yl) with acid results in the formation of rlZ-arene complexes, deprotonation of which returns the rl 1-complexes in a regioselective manner, depending on the substituent; e.g., R = Me gives 94:6 para/meta, while R = CF3 gives 16:84 para/meta (J. R. Sweet and W. A. G. Graham, J. Am. Chem. Soc., 1983, 105, 305; Eq. 25). +

~

R

HBF4 or F S O 3 H ,.Re(CO)(NO)Cp C H2Cl2, -78 *C

i~,~

Re(CO)(NO)Co X

R = H, Me, or CF3

Et3N

R

(25)

163 Low yield of a dirhenium arene complex, in which both rheniums are rl 2bound, is obtained on photolysis of C5Me5Re(CO)3 in benzene solution. The bonding arrangement of the product complex was determined crystallographically (H. van der Heijden, A. G. Orpen, and P. Pasman, J. Chem. Soc., Chem. Commun., 1985, 1576; Eq. 26). It has also been shown that rl2-complexes of selenophene can be prepared directly by displacement of tetrahydrofuran ligand from CsMesRe(CO)2(THF); the NMR spectrum of this complex shows the characteristic upfield shift expected for protons on the rl2-coordinated double bond, and the structure was confirmed by X-ray crystallography (M-G. Choi and R. J. Angelici, J. Am. Chem. Soc., 1990, 112, 7811; Eq. 27). Re(CO)2C P* Cp'Re(CO) 3

by, Phil

=

[CP'2Re2(CO)s ] + (rle.CeHeReCp *)

+

(26) Re(CO).eC p" (5%)

Cp'Re(CO)2(THF) +

~ Se

THF,rl, 7h 450

~)..~Re(CO)2Cp.

(27)

Se

2.3 1"11Complexes Reaction of aromatic ketones or aldehydes with PhCH2Mn(CO)5 leads to the product of ortho-metalation, a ~-aryl-manganese complex, which can be converted to the corresponding palladium complex by treatment with PdC12. The Pd complex undergoes the usual Heck-type reactions with olefinic compounds (L. H. P. Gommans, L. Main, and B. K. Nicholson, J. Chem. Soc., Chem. Commun., 1987, 761). Perhaps more interesting is the observation that direct reaction of the aryl-Mn complex with alkynes affords indene derivatives (N. P. Robinson, L. Main, and B. K. Nicholson, J. Organomet. Chem., 1989, 364, C37; Eq. 28, the formation of indenones from aldehydes is presumably due to oxidation of the initially formed indenols). A study of regioselectivity during the ortho-metalation of meta substituted acetophenones has been reported, and it has been found that activation of the aryl-Mn complex by reaction with Me3NO (to remove one CO ligand) allows direct coupling with alkynes in reproducibly good yields (L. S. Liebeskind et al., J. Org. Chem., 1989, 54, 669; Eq. 29). Analogous coupling reactions between rll-arylFe(CO)2Cp and alkynes, to give indenones, has also been recorded (I. R. Butler et al., J. Chem. Soc., Chem. Commun., 1987, 439). R1 ~Mn~(C 1::12

R1 + 0)4

i II

=Me: PhH, A

M j ~ ~

Hq4

a2'~'~'~ R3

R2 = H, R3 = R4 = ph (97%) R2=R 3=1:14=H (60%) R2 = H, R3 = R4 = SiMe 3 (8%) a2 = R3 = H, I:!4 = Ph (43%)

164 R1

O

J~Mn~(C

;+

R2

0)4

PhH,R'~=H~~ / - - A R2"'.,,,,~" ~ R3

Me

(CO~Mrl'---O

Me

~~'*~O

R4 (28) R2= H, R3 = R4 = Ph (56%) R3 R2 = NMe2, R3 = R4 = Ph (46%)

PhC H2Mn(C heptane, A O)5'~M

g~(C

Me

+

(29)

0)4 X

1) Me3NO /

X

X X = H (76%) X - F (85%); 4.5:1 X = CI (86%)" 1:1

2) RCCR~.,,, / Me " "

{~~H

x B, (6SO/o):14

X = OMe (94%); 2.1:1

'

X = CF3 (85%); 0:100 X = CN (11%)" 0:100

R X=H (60-77%)

An extensive series of applications of this chemistry to the functionalization of terpenoids in the podocarpic acid family have been reported by Woodgate and co-workers. The objective is to construct the steroidal ring system by attachment of the five-membered D ring, and some examples are given in Eq. 30 and 31. (R. C. Cambie, M. R. Metzler, P. S. Rutledge, and P. D. Woodgate, J. Organomet. Chem., 1990, 381, C26; R. C. Cambie et al., ibid., 1990, 398, C22; 1992, 431, 177; 1992, 429, 41; 1992, 429, 59; 1994, 464, 171; 1994, 467,237; 1992, 425, 59; 1992, 426, 213). OMeR / ~ Mer~ IT/O/~ ,~~V MeO2C R2 ~

O Me

R 1 Me

~

O~,~ ~rOH Me3NO' _1) eCN

-Mn(cO)4

2) HC-=CH

Me

Met"

IT ,~

W

MeO2C~ Me

(30)

R=H (95%) R = Me (92%)

R2 R3 ~ R3 1) Me3NO, PhCH2Mn(CO)5, MeL IJ MeCN heptane, A ~~/In(CO)4 -[ t L /" ~.. "'""'~d 2) RCH=CH2 R Me R1 = CO2Me, R2 = R3= H (96%) R1 = CH2OMe, R2= R3 = H (97%) R1 = CO2Me, R2 = OMe, R3 = H (97%) RI=cO2Me,R 2=OMe, R3=cO 2Me (92%)

R2 R3 Me

R

e.g. R = CO2Me" 60% 49%

59% 61%

(31)

165 3. Iron, Ruthenium and Osmium 3.1 176 Complexes

The standard method of preparation of arene-FeCp cations is to treat the arene with ferrocene in the presence of aluminum chloride and aluminum metal (the latter to reduce ferricinium produced during the reaction). This method has been used to effect the complexation of a number of heterocyclic bis(arene) derivatives, giving mono- or di- FeCp complexes (C. C. Lee, A. Piorko, and R. G. Sutherland, J. Organomet. Chem., 1983, 248, 357). A useful alternative that avoids the use of Lewis acid is to prepare the analogous arene-FeCp* cations (Cp* = rl5-C5Me5) by reaction of [Cp*Fe(CO)3IPF6 with the aromatic compound. The Cp*Fe(CO)3 cation is itself prepared in 67% yield by reaction of Cp*Fe(CO)2Br with CO in the presence of A1C13 in heptane at 60 ~ followed by treatment of the reaction mixture with HPF6; the corresponding CpFe(CO)3 cation is too unstable to isolate in this way (D. Catheline and D. Astruc, J. Organomet. Chem., 1982, 226, C52). Arene-RuCp complexes are a useful alternative to the iron derivatives for many synthetic applications. Although the cost of ruthenium makes them somewhat less attractive as stoichiometric intermediates, the complexing reagent can usually be recovered in good yield during demetalation and recycled. A number of methods are available for the preparation of areneRuLn complexes: reaction of a cyclohexadiene with RuC13 gives an areneRuC12 oligomer which can be converted to areneRuC12L on treatment with the appropriate ligand (L - DMSO, PPh3, P(OEt)3, etc.; T. J. Beasley et al., Organometallics, 1993, 12, 4599); treatment of [Ru(rl-arenel)Cl2]2 or [Cp*MCI2]2 (M = Ru, Rh, or Ir) with arene 2 in refluxing CF3CO2H affords high yields of [Ru(q-arenel)(rl-arene2)] 2+ or [Cp*M(rl-arene2)] 2+, respectively (M. I. Rybinskaya, A. R. Kudinov, and V. S. Kaganovich, J. Organomet. Chem., 1983, 246,279); reaction of mesitylene with RuCI3 in the presence of AIC13 and A1 (heptane, reflux, 8h), followed by anion exchange with NaBPh4, affords [bis(mesitylene)Ru][BPh4] in 55% yield (M. I. Rybinskaya, V. S. Kaganovich, and A. R. Kudinov, J. Organomet. Chem., 1982, 235,215). In contrast to ferrocene, ruthenocene is difficult to convert to arene-RuCp by ligand exchange and requires more forcing conditions: arene/Cp2Ru/A1Cl3/Al/H20(drops)/autoclave ca. 130 ~ Yields are still variable (N. A. Vol'kenau et al., J. Organomet. Chem., 1985, 288, 341). Another, less general method for the formation of arene-RuCp cations is via an acetylene insertion/ring expansion which occurs on treatment of cyclobutadiene-Ru(CO)Cp complexes with alkynes under photochemical conditions (M. Crocker et al., J. Chem. Soc., Chem. Commun., 1984, 1141). Finally, the neutral (rl6-naphthalene)Ru(COD) complex has been prepared in 10-20% yield by reaction of [{RuC12(rl4-COD)}n] with Li-naphthalenide,

166 and characterized by X-ray crystallography (M. Crocker et al., J. Chem. Soc., Dalton Trans., 1990, 2299). The conformational effect of attaching a cyclopentadienyliron(+ 1) moiety to hexakis(phenylethyl)benzene has been reported. The structures of the uncomplexed and complexed molecules are shown in Figure 2, and it can be seen that the metal is sufficiently bulky to force all the substituents into a normally unfavorable conformation (M. Zaworotko et al., Organometallics, 1991, 10, 1806). Figure 2: Effect of FeCp Complexation on Conformation of Substituted Arenes +

CH2Ph

C H2Ph

FeCp

C H2Ph

PFs

C H2Ph

Electron transfer reactions of a number of arene-FeCp and bis(arene)Fe complexes have been studied, in anticipation that these systems may be used in catalytic redox processes or in materials applications. A short review appeared in 1986 (D. Astruc, Acc. Chem. Res., 1986, 19, 377). Reduction of the yellow CpFe(II)C6R6 monocations, either electrochemically or by using Na/Hg amalgam, results in their conversion to green 19-electron CpFe(I)C6R6 electroneutral species. The hexaalkylbenzene complexes, usually formed in quantitative yield, are thermally stable and have been characterized by a variety of techniques, such as elemental analysis, mass spectrometry, infrared, EPR, 1H and 13C NMR, UV-VIS, and Mrssbauer spectroscopy. From these studies it is concluded that the HOMO of the Fe(I) complexes has high metal character. Complexes having fewer alkyl groups tend to dimerize during the reduction, dimerization being sterically inhibited for the peralkylated compounds (J-R. Hamon, D. Astruc, and P. Michaud, J. Am. Chem. Soc., 1981,103, 758). Hexamethylbenzene-FeCp cation forms charge transfer complexes with tetracyanoquinodimethane (TCNQ) and phenazine, but powdered samples of these compounds have very low conductivity. (M-H. Desbois, P. Michaud, and D. Astruc, J. Chem. Soc., Chem. Commun., 1985, 450). On the other hand, treatment of [arene-FeCp]I with TCNQ results in the formation of charge transfer complexes of structure [arene-FeCp]+[(TCNQ)2] - which can be obtained as dark green needles by slow cooling of the reaction mixture in acetonitrile as solvent. The X-ray structures of these compounds show segregated stacks of arene-FeCp and TCNQ 0.5-, and the compounds show activated d.c. conductivities of 0.21 and 4.13 ohm 1 cm -1 (arene = 1,3,5C6H3Me3 or C6Me6, respectively; R-M Lequan, et al., J. Chem. Soc., Chem. Commun., 1985, 116). Charge transfer complexes have also been

167 obtained by treatment of bis(arene) iron(II) and ruthenium(II) with hexacyanotrimethylenecyclopropane dianion. X-ray crystal structures show stacks of alternating (arene)2M and [C6(CN)6] with small interplanar distances (<3.30A), and the complexes show intense optical absorptions indicative of charge transfer interactions (M. D. Ward, Organometallics, 1987, 6, 754; see also: M. D. Ward and D. C. Johnson, Inorg. Chem., 1987, 26, 4213). Stable localized mixed-valence complexes containing Fe(I) have been prepared and studied by EPR and M/3ssbauer spectroscopy (M-H. Desbois et al., J. Chem. Soc., Chem. Commun., 1985, 447; J. Am. Chem. Soc., 1985, 107, 5280; Eq. 32). Cyclic voltammetry on these 36-electron Fe(II)/Fe(II) complexes show three quasi reversible waves, corresponding to four oxidation states" Fe(II)Fe(llI)c~Fe(lI)Fe(II)c:~Fe(I)Fe(II)c:~Fe(0)Fe(II)(MH Desbois et al., J. Chem. Soc., Chem. Commun., 1985,447). Similarly, the bis(arene)dicyclopentadienyldiiron complexes, shown in Equation 33, give five mixed valence states in their cyclic voltammograms" Fe(II)Fe(II)r Fe(ll)Fe(l)c=:,Fe(1)Fe(I)c~Fe(0)Fe(I)c:~Fe(0)Fe(0). These complexes range from 36 to 40 electron; the parent benzene Fe(II)Fe(I) complex is unstable, but the corresponding hexamethylbenzene derivative shows greater stability, and can be obtained as a purple air-sensitive crystalline solid in 80% yield by reduction with Na/Hg amalgam (M-H. Desbois et al., J. Am. Chem. Soc., 1985, 107, 5280). Arene-FeCp cations can also be oxidized; treatment with SbCI5 in methylene chloride at 203K gives [arene-FeCp] 2§ which have been characterized by EPR spectroscopy (S. P. Solodovnikov et al., J. Organomet. Chem., 1980, 201, C45). Fe

Fe

1 equiv C6Mes

~

2equivAICl3 ~ ~ 20~176

Fe

Na/Hg

- ~ .~~~

~Fe(ll)Fe(ll)

(32)

Fe(I)Fe(ll)

36e

37e

Fe +

NOBF4 Fe(ll)Fe(ll) 36e

Fe

~ Na2S203 Fe(ll)Fe(lll) 35e R

Fe Fe

ExcessC 61:t6,

AlCl3

R = H or Me

~

R

R ~ §

R

(a3)

R Fe+R Ra " " a

R

Fe(ll)Fe(ll) 36e

There has also been substantial interest in the redox behavior of arene-RuCp cations. An octamethylnaphthalene complex has been prepared and shown

168 to undergo reduction to give an q4-bound species, characterized by crystallography (Eq. 34). The interplanar angle (41.5 ~ is very characteristic of cyclohexadiene-metal complexes. (J. W. Hull, Jr., and W. L. Gladfelter, Organometallics, 1984, 3, 605). A method has been published for showing that apparent two-electron reductions of (T1-C6Me6)2Ru(II) by cyclic voltammetry are sequential one-electron reductions, in cases where the second reduction occurs at similar potential but is much slower than the first (D. T. Pierce and W. E. Geiger, J. Am. Chem. Soc., 1989, 111, 7636). solvent, A

+ [RuCI,2(arene)]2

AICI3, C IC H2C H2CI ,~ "

(34)

or

Ag B F4 then C F3C O2H, A 72 - 94%

Na/Hg I 47-73%

Arene = 1,2,3,4-C 6H2Me4; 1,3,5-CsH3Me 3"

H 1,3,5-CsH3Et3; 1,3,5-CsH3(i-Pr)3; 1-Me-4-(i-Pr)-C 6

~ Ru(arene)

Some interesting helically twisted multiply metalated rubrene derivatives have been prepared and structurally characterized (Eq. 35). The monoruthenium complex has the naphthalene core twisted about the long axis. The compound is blue but exhibits an intense red luminescence; the emission max.imum at 657 nm is red shifted relative to rubrene itself (562 nm). Cyclic voltammetry of the tetraruthenium complex shows reversible one-electron oxidations and reductions that are shifted to more positive potential relative to uncomplexed rubrene, as expected. The primary electrochemical events appear to be associated with the naphthalene system (P. J. Fagan et al., J. Am. Chem. Soc., 1988, 110, 2981; Eq. 36). I equiv [Cp* Ru(MeCN)3][OTI] C H2C 12,rl

(35) 4 equiv ][OTt]~ [Cp'Ru(MeCN) 3 C H 2C i2, repeatedly heat

"C

p"

and remove solvent 85% yield

4[OTI ] (Cp* = C sM es) "C p + R u - ~

I ~ - R u + C p"

169 Boekelheide and co-workers have published a series of papers describing the preparation and characterization of cyclophane complexes of iron and ruthenium, which show mixed valence systems in their redox behavior. A number of examples of the preparation and reactions of these complexes are given in the following equations, and the reader is referred to the primary literature cited here for detailed discussion of their electrochemical characteristics (R. T. Swann and V. Boekelheide, J. Organomet. Chem., 1982, 231, 143; R. G. Finke et al., Organometallics, 1983, 2, 347; R. T. Swann and V. Boekelheide, Tetrahedron Lett., 1984, 25, 899; R. T. Swann, A. W. Hanson, and V. Boekelheide, J. Am. Chem. Soc., 1984, 106, 818; idern., ibid., 1986, 108, 3324, R. H. Voegeli et al., J. Am. Chem. Soc., 1986, 108, 7010; D. K. Plitzko et al., J. Am. Chem. Soc., 1990, 112, 6546; K-D Plitzko and V. Boekelheide, Angew. Chem. Int. Ed. Engl., 1987, 26, 700; K. D. Plitzko et al., J. Am. Chem. Soc., 1990, 112, 6556.) §

Me

FeCp FeCp pF 6-

|

+ cyclophane

Me

P&

= X = R = H (43%) X = H, R = Me (79%) V~ X = OMe, R - Me (61%)

(36) X

§

lerrocene,AICI3, AI, .FeCp methylcycl~ % N 2, A

R _ ~

R = H (44%) R-- Me (43%)

Red-AI, ~

THF, 0 ~

I I~u2.

2BF4"

60%

2PF6"

FeCp

acetone,

, I~u

HCI

(cyclophane 1)

(cyclophane 1RuCI2)2

96%

(cycl~ [Red-AI = sodium

(cyclophanel)Ru

2,

\

CF3C O2H

bis(2-methoxyethoxy)- \ acetone;anion aluminumhydride] \ metathesis .'~ 82%

2 (cyclophane) 2BF 4

(37)

AgBF4 acetone 84%

cyclophane 2 = (cyclophanel)Ru2+(acetone)3 2BF4 ca 82%

Examples of complexes prepared by method of Eq. 38:

(38)

170

(C6Me6RuCI2)2 AgB1:4,acetone, C F3CO2H, A, 2h

[(cyclophane)Ru2(C6Mes)2]4* 4[B F4"]

Cyclophane

(39)

ca 80% Examples of complexes prepared as in Eq. 39:

4BF4"

4BF4

~

4BF4

4BF4

Cyclic voltammetry:

-

- 2+

2e

2e

,..._

,,..._

-2e

-2e

B

(VT NMR experiments suggest mixed valence complex at low temperatures)

(can be isolated in 92% yield)

AI, NaOH, 2BF4- hexane

HCI, acetone 67%

H X- Red-AI,THF, 0 ~

(40)

X"

Pentamethylcyclopentadienylruthenium complexes of cyclophanes have also been studied. The use of [Cp*Ru(CH3CN)3]+[OTf] - (Tf = CF3SO2) for attaching the metal to aromatic rings is particularly advantageous in these systems because of the enhanced solubility of these compounds compared with the Cp-metal hexafluorophosphates. The same reagent has been used to prepare a number of polyarene-ruthenium systems, as outlined in the following equations (P. J. Fagan, M. D. Ward, and J. C. Calabrese, J. Am. Chem. Soc., 1989, 111, 1698). The cyclophane complexes form charge

171 transfer complexes with TCNQ and with hexacyanotrimethylenecyclopropane dianion, the former showing a conductivity of 0.2 ohm 1 cm -1, although other complexes are effectively insulating (M. D. Ward et al., J. Am. Chem. Soc., 1989, 111, 1719). Reaction of anthracene cyclophane with [Cp*Ru(CH3CN)3]+[OTf] - resulted in the formation of dibenzo-pquinodimethane complexes in which the ruthenium prevents polymerization of this very reactive ligand (D. T. Glatzhofer et al., Organometallics, 1991, 10,833). +

RuCp* [Cp*Ru(MeCN)3][oml] ~ 91%

2cg3so 3"

(41)

I+ RuCp* 2+ CoCp*

2+ CoCp*

.

2CF3SO3

I. RuCp*

Examp/es of other comp/exes prepared by the method of Eq. 41: -

9

P Ru*Cp'~l~

Ru+CP" TJ~

Ru+Cp* k

J Y

(as a mixture)

OMe

MeO.,y~Ru+C

LLOJ, cp'Ru+ v ' " o MeO

P~

Ru+Cp *

L ~ -'Ru'c p" T

0

0 .....

Cp*Ru +-

+Cp* (OTI)6

I Cp.Ru § OMe

Cp.Ru+ ~ "-Ru+Cp* ,,-_L~ I (~(OTI) ~,,,E,,, ,

Cp.Ru+_ 0

4

Cp*Ru +-

Ru+Cp*

Ru+Cp

E = C, Si, Ge, Sn, Pb

(OTf') 4

OMe CP* Ru+--~[~J

The arene-FeCp system is quite stable to oxidation, and it is even possible to oxidize methyl groups to carboxylic acids in its presence. Indeed, this provides an excellent method for the preparation of aromatic carboxylic acid and other carbonyl complexes, the direct preparation of which is difficult because of the electron deficient nature of the aromatic ring. Recent examples of this procedure are shown in Eq. 43 - 45. Interestingly, the

172 product ketone complexes react with nucleophiles selectively at the carbonyl group. (C. C. Lee et al., J. Organomet. Chem., 1986, 310, 391; C. C. Lee, U. S. Gill, and R. G. Sutherland, J. Organomet. Chem., 1984, 267, 157). O

F'eCp 4S oc, 3h~ PFe

;~Cp

21 - 38%

PFe

X=OorS X = S: KMnO4 R,

OH

--

R= H (65%)

"~

O

F+eCp

~

PF(

-

'

F+eCp

02

(43)

PFB

23% overall one-pot

R = Me (70%)

1) (a) FeCP2,AICI 3, AI ~ decalin, 140 ~ 6h; .... Cpl~e (b) lh situ, H 2O, Et20 to remove organics; KMnO 4, H20, 60 "C, 10h. 2) NH4PFB

m-C PBA, C H2C12, rellux, 4h 85%

O - ~

A + FeCp

(44)

2PF( O 51% overall

~ ~

+ FeCp 02

(4s)

PFB

The FeCp moiety activates and aromatic ring toward nucleophile addition, or nucleophilic substitution of halide with nucleophiles of moderate reactivity. Chlorobenzene derivatives undergo a d d i t i o n of reactive nucleophiles, such as enolates, with good regioselectivity. Several examples of these Janovsky-type reactions are give in the following equation (R. G. Sutherland et al., J. Chem. Soc., Chem. Commun., 1985, 1296; Can. J. Chem., 1986, 64, 2031). y

X~

y

X=Z=H,Y=NO 2 (55%)

acetone,KOH, H20 X FeCp -

H2COMe

+

PFB

FeCp

X = Z = H, Y = SO2CBH4Me-p (70~ X = Z = H, = COPh (77%) X = Z = H, = CI (mixtures) Z = H, X = Y = CI (60%) Z = H, X = Me, Y = NO2 (50%) X = Z = C I , Y = H (65%) X=Me, Y = H , Z = N O 2 (65%)

(46)

Electron-withdrawing groups, such as C1, NO2, and CO, direct nucleophiles into the ortho position. Nucleophiles such as enolsilanes, cyanide, trichloromethyl anion, etc., also add to give the corresponding dienyl-FeCp complexes (cyanide: R. G. Sutherland et al., J. Organomet. Chem., 1987, 319, 379; J. Org. Chem., 1987, 52, 4618; C. H. Zhang et al., J. Organomet. Chem., 1988, 346, 67; enolsilanes: R. C. Cambie et al., J. Organomet. Chem., 1991,409, 385; trichloromethyl anion: R. G. Sutherland, C. Zhang, and A. Piorko, Tetrahedron Lett., 1990, 31, 6831; pyridazine-N-oxide

173

carbanions: R. C. Cambie et al., J. Organomet. Chem., 1989, 359, C14; 1992, 434, 97). In most cases, the dienyl complexes that result from nucleophile addition are converted to substituted aromatic compounds by oxidative demetalation, using quinone oxidants such as DDQ. It may be noted that methods for converting dienyl-FeCp complexes to cyclohexadienes or cyclohexenones are not yet available. Selected examples of nucleophile addition reactions, showing their regioselectivity, are given in the following equations. X

X

~ ~

NaCN, DMF, . , ~ d, 30 - 40 min ~ . ~ ~ ,,,,CN

+ FeCp PF6

X = NO2 (80%) X X= = COPh CO2Me(82%) (75%)

FeCp

O

O ~F+eCp

(47)

CN

NaCN, DMF, ~ d, 30- 40 min

( 8 5 % )(60%) X=CO X=O FeCp X = S (70%) X = SO2 (75%)

PF6 CI

(48)

CI Bu4NF, THF, rt

R = CHMeCOEI (67%) R = C H2C 02E! (56%)

F+eCp

PF6

Cl CI

Cl -o, + CI

~H 2

(49)

eCp

-o CI

N-N

'N+--N (50)

PF6" CI

OEI

ooo. ec

Cl F*eCp PF6

CI

43%

Cl

Cl THF -78 ~

,'CCl3 d, 30 min

'

70%

FeCp CI

CI

Cl

~

~0013

(51)

Y CI

Nucleophilic substitution reactions of chlorobenzene-FeCp derivatives have been studied quite extensively. Reaction of chlorobenzene-FeCp with sodium azide gives the azidobenzene complex which undergoes explosive decomposition at 165 ~ to give a mixture of aniline-FeCp and cyanoferrocene complexes; the same products are obtained in a controlled reaction by heating at 120 ~ in cyclohexane, and a mechanism for the ring contraction reaction has been proposed (C. C. Lee et al., J. Organomet. Chem., 1981, 220, 181). Reaction of chlorobenzene-FeCp complexes with amines, usually in the presence of mild base such as K2CO3 gives good yields of the corresponding aminobenzene-FeCp complexes, and the primary amine derivatives can be oxidized to nitrobenzene complexes by treatment with H202 in hot trifluoroacetic acid (C. C. Lee et al., J. Organomet. Chem., 1982, 231, 151). Several papers describe the use of stabilized enolates, such as malonates, sulphonylacetates, cyanoacetates, and

174

[3-keto esters, for nucleophilic substitutions. Interestingly, when these reactions are carried out in the presence of excess base (such as K2CO3 or KOBu t) monosubstitution of dichlorobenzene derivatives can be effected. The selectivity that is possible during these reactions is due to the in situ deprotonation of the initially formed adduct at the now very acidic benzylic position, to give a methylene-cyclohexadienyl-FeCp complex that is unreactive towards nucleophiles. Also noteworthy is the observation that NO2 can be used as a leaving group. Several examples of these reactions are given in the following equations (R. M. Moriarty, U. S. Gill, and Y. Ku, Polyhedron, 1988, 7, 2685; R. M. Moriarty and U.S. Gill, Organometallics, 1986, 5, 253; A. S. Abd-E1-Aziz, C. C. Lee, A. Piorko, and R. G. Sutherland, Synth. Commun., 1988, 18, 291; idem, J. Organomet. Chem., 1988, 348, 95; A. Piorko et al., J. Chem. Soc., Perkin Trans. 1, 1989, 469; A. S. Abd-EI-Aziz and C. R. de Denus, Synth. Commun. 1992, 22, 581; Idem, J. Chem. Soc., Perkin Trans. 1, 1993, 293). CI

~ ~ R

+ FeCp PF6"

CH(X)(Y) ]~~ + FeCp R PF6

(52) 2) NH4PF6,H20 50 - 83% X,Y = (CO2EI)2; (COMe)(CO2Et); R = H; p-CI; m-CI; o-CI; p - M e (SO2Ph)(COMe);(SO2Ph)(CO2Et); (COMe)z; (COPh)(COMe); (COCH2CMe2CHzCO); (Ph)COPh) CH(X)(Y) CH(X)(Y) ~ ~ FeCp + vacuum ~ subl 2~imati0on 0 (53) R pF653 - 93% R

X Me

1) CH2(X)(Y),K2CO3, DMF, 25 ~ 5 - 6h

Me

Nu NuH' K2CO3'Me~ M e DMF

zX

Nu Me,,~Me (54)

I,~.~"-F eCp 51 _82O~o I , . ~ ' ~ - FeCp 72.7~O/o PF6" pFe" X = CI or NO2;Null = Me2NH,BuNH2, pyrrolidine,EtOH, PhOH,p-tolSH O

CI

morpholine, [~N'~ F*eCp pF6- K2c 03, etc. ~ . .

I~-~CMe(CO2EI) 2

78%

(55) FeCp pF6" Me(C O2Et)2

Dichlorobenzene-FeCp complexes also react selectively with phenoxide nucleophiles and with amines, allowing access to a variety of unsymmetrically substituted complexes from relatively simple starting materials; this selectivity for the preparation of unsymmetrical triaryl diethers is not possible using the classical Ullmann condensation reaction, and offers a number of opportunities for the construction of unusual isoregic polymers, summarized in the following equations (A. S. Abd-E1-Aziz and D.

175 C. Schriemer, Inorg. Chim. Acta., 1992, 202, 123; A. S. Abd-El-Aziz, D. C. Schriemer and C. R. de Denus, Organometallics, 1994, 13, 374; A. J. Pearson, J. G. Park, and P. Zhu, J. Org. Chem., 1992, 57, 3583; C. C. Lee et al., J. Organomet. Chem., 1986, 315, 79; A. S. Abd-E1-Aziz et al., Organometallics, 1994, 13, 2299-2308; A. J. Pearson and A. M. Gelormini, Macromolecules, 1994, 27, 3675). Removal of the FeCp group is effected fairly easily by pyrolytic sublimation or by photolysis in acetonitrile, the latter being preferable when thermally sensitive functionality is present (for detailed studies on this ligand disengagement reaction, see: A. M. McNair, J. L. Schrenk, and K. R. Mann, Inorg. Chem. 1984, 23, 2633; A. M. McNair and K. R. Mann, Inorg. Chem., 1986, 25, 2519; T. P. Gill and K. R. Mann, Inorg. Chem. 1983, 22, 1986, Organometallics, 1982, 1,485, Inorg. Chem., 1980, 19, 3007, J. Organomet. Chem., 1981, 216, 65; J. L. Schrenk et al., Inorg. Chem., 1986, 25, 3501; D. Catheline and D. Astruc, J. Organomet. Chem., 1984, 272, 417). §

9 I~eCp R

PF6

HO " O - - - ~ O H K2CO3, DMF

CI

(57)

- 96% R= H, Me, CI

74

+

~eCp PFs"

o/_@_ix.

ArlOH, APO~.,,,,,-~/CI PF6" Nail ,THF ~ k'J

CI-~+CI

-,,~\

80 - 99%

FeCp

c

c

Nao

PFe FeCp +

Ar2OH'

NaH,THF

OA~

ArlO

+ PFs FeCp

""~

25 - 87%

NH2 (59)

"~.

PF6" FeCp

.~

C I ~ ~ + C FeCp I PF6"HN~QH

NO2

"-;'\ + "~- NO2 FeCp PFs"

K2C It,99% 03,16hTHF'

CI~N~O

H

(60)

FeCp pFe+

+

FeCp PF6 Excess XH K2C 03, etc. I

58 - 80%

I~i

FeCp PF6

Examples of X: OPh,SCsH4Me- p,

OCH2Ph, OMe, NHC~H4OMe-p, NI--!2, NHNH2, NHMe, NHCH2Ph,CH2COMe, CH(CO2EI)2, CH(COPh)2, CH(COMe)CO2Et

(58)

176 +

high dilution 1 equiv XH K2C 03, etc

FeCp PF6 ../ y ~~"

50 - 83%

(61)

I

+

+

FeCp PFe

FeCp PFs

-,~./ CI NaO.~

~~0 ~,.

"'~'C O2M e

CI

71%

CI

CO2Me

+

NaO.~ v-OH 82%

FeCp PFo" F/TO~~]~

HO . . . ~

(62) '~""

O" I ~ '

CO2Me

Reactions of 1,2-dichlorobenzene-FeCp comple• with a number of dinuc]eophi]es have been shown to give good yields of heterocyclic products. The phenoxazine and phenothiazine derivatives obtained from decomplexation may be of some pharmacological interest (R. G. Sutherland r al., J. Heterocycl. Chem., 1982, 19, 801; R. C. Cambie et al., J. Organomet. Chem., 1991, 420, 387; Eq. 63). +

§

FeCp PF6

FeCp PFs or THF-DMSO

I

HY-

A _--

(63)

v

X = Y = O , R = H (78%) X=S,Y=O,R=H X = Y = S, R = Me_ (82%) X NH, Y=O, - H (45%) X = NH, Y = S, R = H (23%)

(76%)

(91%) 190%! 94 % (48%) (24%)

Arene-RuCp (and Cp*) cations show reactivity similar to their iron counterparts during nuc]eophi]ic substitution reactions, but problems arise during nucleophile additions. A review appeared in 1988 (R. M. Moriarty, U. S. Gill, and Y. Ku, J. Organomet. Chem., 1988, 350, 157). Addition of hydride (from NaBH4) and PhLi to benzene-RuCp gives the expected dienyl complexes in 55 and 83% yield, respectively, but these reactions have not been studied in great detail. Treatment of the dienyl complexes with Nbromosuccinimide gives the (substituted) arene complex. The same authors showed that chloro- and fluorobenzene complexes undergo nucleophilic substitution on treatment with thiophenoxide, cyanide, hydroxide or piperidine nucleophiles, and that the fluorobenzene complex is the more reactive, as expected. Oxidation of toluene-RuCp to (benzoic acid)-RuCp, and of thiophenoxybenzene-RuCp to (rl6-diphenylsulfone)-RuCp can be effected in ca. 80% yield by treatment with KMnO4, without detriment to the metal moiety. (N. A. Vol'kenau et al., J. Organomet. Chem., 1984, 267, 313). Reaction of chloroarene-RuCp complexes with phenoxide proceeds in much the same way as for the chloroarene-iron analogs, and has been explored as methodology for the synthesis of aromatic polyethers (J. A.

177

Segal, J. Chem. Sot., Chem Commun., 1985, 1338; A. A. Dembek, P. J. Fagan, and M. Marsi, Macromolecules, 1993, 26, 2992; the latter authors used the RuCp* triflate salts and obtained high molecular weight polymers with better solubility than their RuCp hexafluorophosphate counterparts shown in Eq. 65). The construction of unsymmetrical triaryl diethers has also been shown (A. J. Pearson et al., J. Chem. Soc., Chem. Commun., 1989, 1363; A. J. Pearson and J. G. Park, J. Org. Chem., 1992, 57, 1744). Some examples of this chemistry are given in the following equations. §

R+uCp

RuCp PF6"

c,

~p el

50~ 10rain

F6-

CI O

N N 2equiv NaOAr, MF 85 ~ 20 min ' ' O M

e

O

~

+ PF " RuCp 6

11/~~ J[~OMe

O

(64)

O +

RuCp

CII ~

CI PF 6

DMSO, 85 - 90 ~ 2) DMSO, 160 ~

O 1.5h

O

(65) n

70 - 75%

X = CO or CMe2 M n = 6170, M w = 15600

The main advantage to using RuCp to activate the arene lies in the relatively mild conditions that are used to attach the metal, which tolerate the presence of sensitive functionality on the aromatic molecule. For example, complexes of protected 4-chlorophenylalanine can be prepared in good yield, without racemization, and coupled with phenoxides derived from arylamino acids. Decomplexation can also be effected in the presence of peptide functionality, without racemization, and this chemistry has been used in a formal synthesis of the angiotensin converting enzyme inhibitor K-13 (Figure 3; A. J. Pearson and K. Lee, J. Org. Chem., 1994, 59, 2304). Figure 3: Applicationof Arene-RutheniumChemistryto the Synthesisof K-13 Cl

[(CH3C N)3RuCp][PF6] ,

CI

.,L

~01,2-dichloroethan 93 - 98%

OR

BocHN

Figure 3 continued.....

"~"~

~1

~ O R BocHN

A

178 OMe ~ O H

[ ~ Me02C. J 0

..... ~-'O---"~/l'~u*t;'P..Lr'-

OMe NaO(2'6-But2)C 6H3 then complex A, i~'~ R C H2C Br -- ~ Me02C., J ~

~" 7.]

Nl-I~oc:

0 C 1"-12CH 2Br

0

'H

8,.,,o

MeO ~

MeO" v OH

steps

-I-IO2C'

"NHAc

NO

(K-13)

Complexation of the aromatic ring of a number of estrone derivatives has been studied; good yields but marginal stereoselectivity was observed. The use of chloroestrone derivatives, coupled with nucleophilic substitution, allows access to potentially useful functionalized estrone derivatives (R. M. Moriarty et al., Organometallics, 1989, 8, 960; J. Chem. Soc., Chem. Commun., 1990, 1765; Eq. 66). The degree of stereoselectivity that is observed during the complexation of ring-C aromatic diterpenoids, that are derived from or related to podocarpic acid, is dependent on the nature of substitution on the molecule (R. C. Cambie et al., J. Organomet. Chem., 1991,409, 263).

o

Nucleophile G .

MeO" ' ~ , + v RuCp PF6"

75-94% MeO

z& '~

G MeO

(66)

RuCp pF6"

Similar reactions of indole-RuCp complexes have been reported. Again, the use of chloroindole derivatives allows the preparation of substituted indoles that are not easily prepared by most standard procedures (R. M. Moriarty, Y. Ku, U. S. Gill, J. Chem. Soc., Chem. Commun., 1987, 1493; Organometallies, 1988, 7, 660; J. Organomet. Chem., 1989, 362, 187; Eq. 67).

179 n2

R1or R2---CI R3= Me: Nucle-ophi 88% le60

[(CH3CN)3RuCPl[PF6] R2 1,2-dichloroethane, I ~ ~ N 40- 50 ~ 15h R

R~~N

- - - - _ _

i~3

80-88%

R~

or

R ~~, (67)

....it ..._. ~,3 IJpi4u I-'16- n

CpRu PFe" Me CpRu PF6 Me R = OMe,CH(CO2Me)2,MeNH, SCH2CO2H,OCH2Ph Deprotonation of bcnzy]ic positions of a]kyi-substituted arcne-EeCp complexes occurs readily to give mcthy]enecyc]ohexadicnyl complexes. Reaction of these complexes with r162 such as aikyl halides, provides useful methods for the functiona]ization and homo]ogation of the side chain. Naturally, there are ]imitations on this methodology, depending on the reactivity of the a]kylating agent and its steric bulk. Pcra]ky]ation has led to the preparation of interesting dendritic molecules. A]kcnr groups can be functionalizcd in a variety of ways in the presence of the arene-EeCp moiety. Several examples of this reactivity are given in the following equations; all alkylation products can be demetalated in the usual way. (D. Astruc et al., J. Am. Chem. Soc., 1979, 101, 5445; C. C. Lee, U. S. Gill, and R. G. Sutherland, J. Organomet. Chem., 1981, 206, 89; D. Astruc et al., J. Am. Chem. Soc., 1981, 103, 7502; J-R. Hamon et al., J. Am. Chem. Soc., 1982, 104, 7549; F. Moulines and D. Astruc, Angew. Chem. Int. Ed. Engl. 1988, 27, 1347; F. Moulines et al., Synlett, 1992, 57; F. Moulines, B. Gloaguer, and D. Astruc, Angew. Chem. Int. Ed. Engl., 1992, 31,458; F. Moulines et al., Angew. Chem. Int. Ed. Engl., 1993, 32, 1075; J. L. Fillaut, R. Boese, and D. Astruc Synlett, 1992, 55; C. Moinet and E. Raoult, J. Organomet. Chem., 1982, 229, C13; S. L. Grundy, A. R. H. Sam, and S. R. Stobart, J. Chem. Soc., Perkin Trans. l, 1989, 1663). Fe*Cp ExcessKOBut'Mel'A ~,/ J i ~ ~ ' ~ e PF6. THF,25 ~ lh -/ "~" "i~"~ PF6

Fe+Cp

Na,Hg~

FeC (68) gr

~'] I Fe§

KOBJ'THF'

r

"~

L .B,

/

Br

L

.B, ~Br (69)

(

~*C

p PF,

::~,J

B~PF:.Br Br

180

/~9 OH

/

H

-BBN" H20 2, hlaOH

~

1)i-Am2BH; ~ 2) 12, NaOH, MeOH " ~ 00~176 I

H

/

I

~LFe+Cp pFs

HO"

.

.I

"1 OH

I

^

F~'I,"~"-p CH=:CHC~=B,, 2 days

PF6

j

=

'LL....J) 1~ ~1' I I I . ~

_

!!

~Fe+C

~, MeCN, PPh3

~ P

_

(70)

=

OR OR Fe+C p I

~

PF6

1) KOBut, THF, RO ROC6H4C H2Br, 40 ~ 1 day

O (71)

2) hv, MeCN, rt, 8h 50 - 6O%

R RO" v OR

NH2 Me , ~ _ . ~ I~J

Fe+Cp PFs"

KOBui, RX, THF ---48-85%

NHR Me . ~ _ _ I ~

Fe+Cp PFs"

RX = Mel, PhCOCI, MeCOCI, EtCOCI R NOH CH2R 1) KOBul, THF T 2) EtONO Fe§ p - Fe+C p 45% ~ PF6PF6"

~

(72)

(73)

181 +

FeCp

§

50 equiv. KOBUt, Mel

64% +

Me,, Me

FeCp (74)

M +

FeCp

KOBut'Mel ~05 ~~~~"

H

+

FeCp

Me,..Me

FeCp

KOBut'Mel ~

Me

(75) Me

(rl6-Arene)2Fe(II) complexes have also been investigated. Because these are dications, they have the potential to undergo consecutive addition of two nucleophiles. It has been found that both nucleophiles add to the same ring, except for peralkylbenzene complexes where steric hindrance prevails. Carbanion nucleophiles do not react with the parent (benzene)2Fe(II) complexes but alkylation of the dienyl complex resulting from hydride addition can be achieved. Two alkyl groups can be introduced stereospecifically by the sequence: hydride addition/alkyl addition/hydride abstraction/alkyl addition. Thus, hydride is used as a "protecting" group. The hydride abstraction reaction, using triphenylcarbenium, has been studied by ESR spectroscopic methods. At -130 ~ the spectra of two radicals were observed, one being iron-centered, and the other an organic radical (triphenylmethyl). As the temperature is raised the iron radical resonance becomes more intense, but at 0 ~ it disappears and signals for the triphenylmethyl radical are observed. These experiments suggest an electron transfer pathway for the hydride abstraction (D. Mandon and D. Astruc, Organometallics, 1989, 8, 2372). A number of reactions of bis(arene)iron complexes and their derived arene(dienyl) complexes are shown below. (D. A. Sweigart, J. Chem. Sot., Chem. Commun., 1980, 1159; A. M. Madonik et al., J. Am. Chem. Sot., 1984, 106, 3381; A. M. Madonik and D. Astruc, J. Am. Chem. Sot., 1984, 106, 2437; D. Mandon, L. Toupet and D. Astruc, J. Am. Chem. Soc., 1986, 108, 1320; D. Mandon and D. Astruc, J. Organomet. Chem., 1986, 307, C27; idem, ibid., 1989, 369, 383; idem, Organometallics, 1990, 9, 341; T. S. Cameron, M. D. Clerk, A. Linden, K. C. Sturge, and M. J. Zaworotko, Organometallics, 1988, 7, 2571.) R

FeC12,AICI3,

2+

80-190~ 1-20h (AICI4")2

(76)

182

Me >-~<" -Me--1 2+

Me ~'-M

e--l +

Me__Me NaBH4,0~ M e _ _ M e .Me"- Fe-'Me ----- Me"- Fe-"Me Me-,~_.L..<,,Me Me-~-.l..<- Me Me---~~ Me Me---~',.I. ~ , Me/ "Me M e ~ Me

"(77)

H

Me~ ~ Me

M

Fe ~9 ~

Me

2 x PhLi

Me

THF"80 ~ <5% yield

Me

~

(78)

Fe Me

Me i

i

Ph Ph Me Me--] 2+ Me MeT+ Me... Me Me"-~~Me MeLi,THF M e ' - - ~ ~ M e MeLi,THF M e ' - - ~ ~ M e Mef =.,-Me = Me" L--.,-Me - .M.e'~" #e ~'Me M e"~.-~l~M e .I00 oC M e,,~_.i':'--Me - Me.~..l_<. Me Me.....~r~.~._Me 370/o M e ~ _ M e -45~ M e - ~ , " ~r~Me Me/ "Me Me!~1e~Me Me" ~j~e i Me Me Me~Me-] 2+ MeF ~ ~ e MMe "--] + Fe-'- Me R" Me R Me~'-~Me Me Me/ Me I H R R = CN; C H2NO2;CH2CO2But Me Me'--~ 2+ Me'--~~Me 4 equiv Me" Fe ~Me

Me.~..j.~_<.Me Me---~~Me Me/ "Me

O

.aB., _

Fe 2+

Et3AI

-

M~

L" Me+ + Me

Me

Me 43 55%

Me Me"-] + M e - - - ~ ~ Me Me ~"

Fe~Me

(81)

CiC H2CH2Cl Me-~..l..<-Me 0~ M e_~./~, . M er--,~ . 93% Me" i~1e-'~~ Et Fe+

PhCH2MgBr

Fe C H2Ph

H

I Ph3C+ 9O 95% -

{ ~ I , , C H2Ph .,FeCI3,0~

O Q F

:CN

F e ~ (82)

"'C N

100% NC

87% C H2Ph

H C H2Ph

(79)

(80)

183 -"-t

Me Mel / Me'--'~~-Me Me".,~_I.~.M Fe-Mee Me .~~

M~~

R

Me__Me 1) PhCOCl M e . - - - ~ ~ M e 2) KOBu=t Me Fe Me Me-~_, l-~.-Me

+

Me,,>.__..<,Me Me__Me Fe Me KOBu' MMee-~...I..K-M e

Me

Me-y4

~

(83)

MO-yF~

so-*~

C H2 R = CH2 Ph (97%)

CHCOPh

3.2 172 Complexes Some interesting and potentially useful (rl2-arene)osmium complexes have been studied by Taube and Harman and their co-workers. Coordination of one double bond to the metal essentially destroys the aromaticity of the molecule and allows a variety of reactions typical of dienes to be effected. Anisole complexes behave more like dienol ethers and show enhanced reactivity towards electrophiles, despite the presence of the positive charge on the metal. The complexes are easily prepared by reaction of the arene with Os(NH3)5(OTf)3 (Tf = CF3SO2) in the presence of magnesium (to reduce Os III to OsII). Electron-donating substituents direct the osmium onto the 2,3-double bond, thereby allowing regiocontrol during the subsequent transformations. A number of examples are shown below. Especially noteworthy is the introduction of substituents onto the estradiol molecule to give non-aromatic steroid derivatives; note also the regiocontrol that is possible with the steroid system: at -35 ~ under mildly basic conditions attack at the angular carbon is observed, while Lewis acid catalysis at 20 ~ gives the product of reaction at C-4 (Eq. 89). (W. D. Harman and H. Taube, J. Am. Chem. Soc., 1987, 109, 1883; W. D. Harman, M. Sekine and H. Taube, J. Am. Chem. Sot., 1988, 110, 5725; M. E. Kopach, J. Gonzales, and W. D. Harman, J. Am. Chem. Soc., 1991, 113, 8972; M. E. Kopach, W. G. Hippie, and W. D. Harman, J. Am. Chem. Soc., 1992, 114, 1736; M. E. Kopach et al., J. Am. Chem. Soc., 1993, 115, 5322; J. Gonzales, M. Sabat, and W. D. Harman, J. Am. Chem. Soc., 1993, 115, 8857; M. E. Kopach and W. D. Harman, J. Am. Chem. Soc., 1994, 116, 6581.) R

00s(N

OMe 0 _

R

R

H3)s(OTI)3~_ o 2+ ___ Mg_ _ OsN (H3s) or 2(OTI) (84) 70 - 90% v 2(OTI) 2+ R= R= Os(NH3)s OMe i-Pr NH2 t-Bu NMe2 Ph COPfi CF3 OMe OMe

2+ -13)s MeCN, rt, 10 minMeOTI 0 - Os(Nl 2(OTI) [ Me

2+ 0 2, H20, H +cal. ~ O Os(NH3)5 2(OTF) NMe

93% M

(85)

184 OH Os(NH3)s 2(OTr)

maleic anhydride

24h 85%

O

OH C{~ 2+ MeOH, H+,A Os(NH3)5 = 2(OTI)

~_ H'~

O ~--%O.~O

~_

>90%

H,~

C O2M

MeO2

| NMe2 CH2=CHCO2MeNMe2 2+ TBSOTI,CD3CN ~ _ _ 2+ Os(Nl-13)5 Os(NH3)5 2(OTI')

(86)

NMe2 R3N,& (87)

2(OTI)

CO2Me ~-OTBS MeO

| NMe2

NMe2

~ , . . , O ")+ s(NH3)5 H-~%~ 2(OTr) MeO

NMe2

Bu4NBH4 H ~ _ 2 +Os(NH3)5 Ce(IV) 93- 98% ~ 2(OTt~ 48 - 51%

OTBS

H~

yield

CO2Me

(88)

CO2Me

MeOH

HO

67%

|HO" L

~ M e

OH C

Oo~ e(IV)

0

[

"

v

equilibrium mixlure

(89)

methyl vinyl ketone

O"- v 69% overall

v

v (97%)

-35 ~ (i-Pr)2NEl

20 ~ Zn(OTI)2

H =o

0 ,-~

v

Transfer of the [Os(NH~)5] 2+ group to 2,6-lutidine is possible, again with regiocontrol, but the 1"1"complex rearranges to a lutidinium ~-complex within hours, and the osmium transfers to nitrogen upon oxidation to Os(III) (R. Cordone and H. Taube, J. Am. Chem. Soc., 1987, 109, 8101). Pyrrole forms rl2-osmium complexes that show reactivity similar to the benzene derivatives, undergoing (presumably non-concerted) cycloadditions, and reactions with electrophiles, as summarized below (R. Cordone, W. D. Harman and H. Taube, J. Am. Chem. Soc., 1989, 111, 5969; W. H. Myers, M. Sabat, and W. D. Harman, J. Am. Chem. Soc., 1991, 113, 6682; W. H. Myers, J. I. Koontz, and W. D. Harman, J. Am. Chem. Soc., 1992, 114, 5684).

185 Me 2+ Os(NH3)s 2,6-1utidine ,,. N ~ ~ 2(OTI') Me

2+ MeN ~~ Os(NH3) 5 -e" 2(OTI') chemically irreversible [Os0")] oxidation Me (9o)

M e ~

[Os]§ MeCN

MHe+.N~~ + [Os00(NH3)4(MeCN)] Me

Me maleic

H

9

Os(NH3)s(OTI)3

Mo~ DME

H

~

N

anhydride, H H I1,5 min [Os]~ t~~O O +[Os]~ 2+ : Os(NH3)s 2(OTf) O O 4:1 ratioexo/endo

0

(91)

4. Chromium, Molybdenum and Tungsten

In this series the last review of aromatic compounds of the transition elements, including metal ~-arene complexes of Cr, Mo, and W, was published in 1974 (M. A. Bennett, "Rodd's Chemistry of Carbon Compounds", 2nd edn., Vol III Part B, ed. S. Coffey, 1974, 357). In the intervening decades there have been many reviews published in this area, reflecting the rapid growth in studies not only of the preparations and properties of the (q6-arene) complexes of the Group 6 metals, but particularly with respect to their applications in the synthesis of organic (metal-free) molecules. In the latter regard the development of routes which provide enantioselective syntheses as a consequence of transfer of planar chirality due to an (o-or m-differentially disubstituted ~6-arene)Cr(CO)3 moiety is particularly noteworthy. The primary literature in the general area of (q6-arene)M(CO)3 complexes (M - Cr, Mo, W) has been summarized regularly in compilations of annual surveys (e.g. Annual Survey for 1991; L. S. Hegedus, J. Organomet. Chem., 1993, 457, 167; and preceding surveys), which include references to the large number of specialist reviews then available. Consequently, this review will restrict its coverage of the literature mainly to 1990-1993, and to applications of (q6-arene)M(CO)3 complexes in organic chemistry. Literature cited is selective rather than comprehensive, the citations themselves leading to relevant related references.

186 4.1 ( fl6-Arene)Cr(CO)3 Complexes (a) Preoarations This section necessarily includes use of some of the reactions of (116arene)Cr(CO)3 complexes which are discussed further subsequently. By far the most common method for the preparation of an (rl6-arene)Cr(CO)3 complex continues to be thermally-promoted exchange from hexacarbonylchromium. Although the Mahaffy-Pauson procedure (C. A. L. Mahaffy and P. L. Pauson, Inorg. Synth., 1990, 28, 136), which uses a mixture of Bu20-THF (ca 10-12:1), still enjoys widespread use it is sometimes complicated by low yields due to thermal or autocatalytic decomposition of the required T16 complex during the relatively long reaction times. In an attempt to minimize or avoid these problems, Toma has conducted a study of a higher temperature/shortened time method using Cr(CO)6 in the presence of various organic additives as catalyst (M. Hudecek and S. Toma, J. Organomet. Chem., 1990, 393, 115; M. Hudecek and S. Toma., J. Organomet, Chem., 1991,406, 147; M. Hudecek, V. Gajda, and S. Toma, J. Organomet. Chem., 1991, 413, 155; P. Hrnciar and S. Toma, J. Organomet, Chem., 1991, 413, 161 ;P. Hrnciar et al., Coll. Czech. Chem. Commun., 1991, 56, 1477; P. Hrnciar et al., J. Organomet. Chem., 1994, 464, 65). For example, the inclusion of 1-3 molar equivalents of BuOAc in refluxing decalin led in a relatively short time to the formation of (rl6-C6HsCH3)Cr(CO)3 in high yield, using a condenser modified to minimize not only exposure of the hot solution to air but also loss of Cr(CO)6 from the solution due to sublimation. Similarly, (116C6H5NH2)Cr(CO)3 (2 h, 80%), (q6-~5CO2Me)Cr(CO)3 (76%; cf 15%), (q6-C6H5CONMe2)Cr(CO)3 (1 h, 23%), and (rlb-C6H5OH)Cr(CO)3 (14 h, 41%), amongst a range of functionalized arenes, were accessible. On the other hand, C6H5CHO, C6H5CH2C1, C6H5NO2, C6H5SH, and C6H5CH=CHCOCH=CHCOC6H5 were not suitable substrates under these conditions. Notably, (C6HsC1)Cr(CO)3 was prepared in 58% yield in the presence of BuOAc as catalyst, whereas dehalogenation was a significant problem in its absence. For complexes which can be produced as a mixture of regioisomers and/or diastereomers, the relatively high temperature of a thermally-induced exchange can promote isomerization of a kinetically formed product to the thermodynamically preferred isomer. For situations in which either regio- or stereo-control of subsequent C-C bond-forming reactions is required (see later) it is often desirable to use an arene exchange process at a lower temperature. In this regard, the use of (q6-naphthalene)Cr(CO)3 as the donor reagent (E. P. Ktindig et al., J. Organomet. Chem., 1985, 286, 183, J. A. S. Howell et al., J. Organomet. Chem., 1985,294, C1) is often preferable to the use of either (MeCN)xCr(CO)6_x (for a comment on the composition of this mixture as usually generated, see S. L. Ellis et al., J. Organomet. Chem., 1993, 444, 95) or Py3Cr(CO)3 or (NH3)3Cr(CO)3. For example, whereas

187 treatment of starphenylene or its hexakis(trimethylsilyl) derivative with (NH3)3Cr(CO)3 in refluxing dioxane for 14 h gave selectively the exo-rl 6Cr(CO)3 isomer of each ligand, (q6-C10H8)Cr(CO) 3 in THF at 50 ~ afforded selectively the regioisomeric endo complex (M. Nambu et al., J. Am. Chem. Soc., 1993, 115, 6138). R

exiting ~ R R R

dor~g R R = H, Me3Si

R

These results reflect the preference for kinetically-controlled coordination to the more nucleophilic central (endo) "cyclohexatriene" ring, but the thermodynamic stability of the rl6-complexed benzenoid (exo) ring. Incidentally, the endo regioisomer is the first example of an rl~ complex which demonstrates not only the ubiquitous metal-tripod rotation (AH* 46.4 kJ mo1-1) but also intramolecular metal-arene (endo-exo) exchange (AH* ca 115 kJ mol-1). Ligand exchange with (rlh-1methylpyrrole)Cr(CQ)3 has recently been used for the direct syntheses in good yields of the rl~ complexes of some nitrogen heteroaromatic compounds at or below room temperature in CH2C12 or EtOAc (A. Goti and M. F. Semmelhack, J. Organomet. Chem., 1994, 470, C4). Photolytically-promoted generation of (rl6-arene)Cr(CO)3 complexes has been used much less frequently. The scope and limitations of the lightinduced exchange from Cr(CO)6 have been investigated (G. B. M. Kostermans et al., J. Organomet. Chem., 1989, 363, 291); although the yields are generally lower (e.g. C6HhNMe2, 21%; C6HhC1, 0%; C6HhCO2Me, 19%, c f above) than those from a thermally-promoted process, the experimental conditions are relatively mild. This advantage has been exploited in the synthesis of the rl6-Cr(CO)3 complex of benzo[3,4c]thiophene (J. P. Selegue and K. A. Swardt, J. Am. Chem. Soc., 1993, 115, 6448). |

(OC)3Cr /

(OC)3Cr

(OC)3Cr

Since the free ligand degrades within minutes at room temperature, neither (EtCN)3Cr(CO)3, nor (NH3)3Cr(CO)3, nor (rl6-C10H8)Cr(CO)3 afforded any of the required complex on heating. The rlr-Cr(CO)3 complex of thiophene itself has recently been formed in 75% yield by exchange from (1"16-

188 C10H8)Cr(CO)3 in THF at 80 ~ (M. Struharik and S. Toma, J. Organomet. Chem., 1994, 464, 59). The rI6-Cr(CO)3 complexes of a number of polycyclic aromatic hydrocarbons have been synthesized by treatment of the arene at room temperature with (NH3)3Cr(CO)3 and BF3.OEt2 for 4-8 days (J. A. Morley and N. F. Woolsey, J. Org. Chem., 1992, 57, 6487). The Cr(CO)3 group can be transferred readily and diastereoselectively to an enantioenriched or enantiopure ligand having a stereogenic center at a benzylic site. For example, (rl6-C10H8)Cr(CO)3 has been used to generate the following complex with high diastereoselectivity (M. Uemura, R. Miyake, and Y. Hayashi, J. Chem. Soc., Chem. Commun., 1991, 1696; M. Uemura et al., J. Org. Chem., 1986, 51, 2859). Me 0

Me

H

Et20(THF)

Et

7,,.~.~0 (OC)3C(

H

(92)

El

[The designation of R or S is based on the Cahn-Ingo]d-Pre]og rule (see K. Sch]ogl in Topics in Stereochemistry, E. L. Erie] and N. L. A]]inger Eds., Wiley-Interscience, New York, 1967, 1, 39)]. In a number of complexes derived from optically active 1-tetralols, the mild conditions available by the naphthalene exchange procedure gave greater than 99% diastereoselectivity (H. G. Schmalz, B. Millies, J. W. Bats et al., Angew. Chem. Int. Ed. Eng., 1992, 31, 631). OH

RI R2

OH

(i), (ii), or (iii)

~~.

RI

OH

+

"i~

R2

R1

(93)

Ra

R3 (OC)3Cr.-" R3 (O R1 = R 2 = R 3 = H ; R I = R 3=H,R 2=OMe; R I=R2=OMe,R 3=H;R I=H,R2=R3=OMe

Rcaction conditions: (i) (TI6-CIoH8)Cr(CO)3(1.2 eq.), THF (1.5 eq), Et20, 70 ~ ; 90%, >99:1 (ii) Cr(CO)6 (1.1 eq), Bu20-THF(10:1), reflux: 30 h, 65%, 90:10; 41 h 28%, 52:48; (iii) Cr(CO)6 (1.1 eq), Bu20-CTH16(l:l)-cat. THF, reflux: 74%-70%, 93:7-99:1

Although the Kfindig transfer method also afforded the syn-l-tetralol complex in excellent yield and diastereoselectivity, use of the more accessible Cr(CO)6 as reagent gave good yields and stereoselection providing that Bu20-heptane (1:1) was used as solvent, with only a catalytic amount of THF (1:60 v/v). The syn:anti ratio decreased continuously during these conversions since the q~ unit can decomplex and then transfer to the opposite face of the arene ring to generate the thermodynamically preferred diastereomer. For any particular substrate

189 capable of giving a mixture of isomeric complexes it is often necessary to survey a range of experimental procedures with a variety of Cr(CO)3 donors in order to define optimum conditions to deliver the target complex with high selectivity. In a fundamentally different route, the well-known D6tz annulation sequence using a Fischer-type alkynylaminocarbene chromium complex provides a route to a diastereomerically pure (rl6-arene)Cr(CO)3 complex, the coordinated arene ring being generated during the annulation (K. H. Drtz, T. D. Schaefer, and K. Harms, Synthesis, 1992, 146). In a complementary approach which takes advantage of existing functionality, (rl6-o - or m-disubstituted benzaldehyde)Cr(CO)3 complexes, which have planar chirality, can be reduced enantioselectively (see later) using commercial bakers' yeast to give (at 50% conversion) a benzylic alcohol with good to high e.e. (S. Top et al., J. Organomet. Chem., 1991,

413, 125). ~'Q--X~C HO - ~ (OC)3Cr

~ C H O .= ~

R

(OC)3Cr

R

yeast 20 ~

(94)

+

+

R

R

~--~-I~CHO (oc)3cr

~--~I~CH2OH (oc)3cr

R = OMe, Me, CI, F, SiMe3 For R = OMe the kinetically-resolved aldehyde (1S) was recovered in 100% e.e., while the benzylic alcohol was isolated in 45% yield and 100% e.e., but with the antipodal absolute configuration (1R). The direction of hydride delivery leading to the observed enantioselectivity was rationalized on the basis of Prelog's rule. In a similar approach, a lipase isolated from either Pseudomonas fluorescens or Candida cylindracea has been used to generate products of opposite configuration either (i) during the monoacylation of [q6_l,2_bis(hydroxymethyl)benzene]Cr(CO)3with vinyl acetate or vinyl palmitate or vinyl benzoate; or (ii) during alcoholysis of the corresponding diesters of the complex with 1-butanol; or (iii) during acylation of (rl oC6H5CH2OH)Cr(CO)3 using racemic vinyl 2-phenoxypropanoate or vinyl 2-phenylpropanoate (Y. Yamazaki and K. Hosone, Agric. Biol. Chem., 1990, 54, 3357). Hydrolysis using pig liver esterase of the meso diesters [oC6H4(CH2CO2R)21Cr(CO)3 (R = Me, Et) gives the half-ester in good yield and with >94% e.e., the pro-S pendant ester being cleaved preferentially (B. Noezieux et al., Tetrahedron: Asymm., 1992, 3, 375). The rl6-Cr(CO)3 complexes of some o-substituted (Me3Si, Me, OMe) benzyl alcohols are resolved kinetically by lipase-catalyzed asymmetric transesterification with isopropenyl acetate. The S alcohol reacted enantioselectively (K. Nakamura et al., Tetrahedron Lett., 1990, 31, 3603).

190 Direct asymmetric introduction of the Cr(CO)3 moiety onto a 1,2disubstituted arene ring has been achieved (A. Alexakis et al., J. Am. Chem. Soc., 1992, 114, 8288), the aminal derived from (R,R)-l,2-bis(Nmethylamino)cyclohexane being very efficient in directing highly stereoselective transfer of Cr(CO)3 from the rl6-naphthalene complex at room temperature. Inversion of planar chirality was effected by submitting the resulting kinetically formed 2S 1"16 complex to the Mahaffy-Pauson solvent mixture at 140 ~ giving the 2R diastereomer. MeN~4e

(TI6_CloHs)Cr(CO)3 R

MeN_

NMe

Bu20-THF 140 ~

r.t. THF 4 days R = Me, 80%

enantiopure

2R 95%

(95) 01"(00)3 R = Me, 94% d.e.

R = Me, OMe

20 h

CHO

CHO

H3O§

Advantage has been taken of the enhanced susceptibility of an (1"16haloarene)Cr(CO)3 complex to undergo SNAr reactions to provide a catalytic asymmetric synthesis of an optically active molecule. Thus, treatment of (vl6-1,2-dichlorobenzene)Cr(CO)3 (a m e s o complex) with either a vinylmetal or a vinylborane reagent in the presence of an optically active ~:-allylpalladium catalyst [L* = BINAP or (S,R)-RPFA] resulted in a monocoupled product [CH2=CHZnCI, 44%; ratio of mono:di improved from 2:1 to 19:1 using CH2=C(Me)B(OH)2] with moderate enantioselectivity (CH2=CHZnCI, 42% e.e.) (M. Uemura, H. Nishimura, and T. Hayashi, Tetrahedron Lett., 1993, 34, 107). That is, one of the enantiotopic C-CI bonds reacts selectively with a non-racemic Pd(0) species to form a PdCarene bond, leading to the optically-enriched vinylated arene complex.

(OC)3Cr

!

CH2=CH.M

I

PdCI(=-allyl) 2 L* (0C)3Cs

(96)

The increased ability of (~6-arene)Cr(CO)3 complexes to undergo arene deprotonation (see later) has also been utilized. Thus, the asymmetric directed o r t h o metalation of a tartrate-derived aryl aldehyde Cr(CO)3 complex gives, after quenching with an electrophile, (q6-o-disubstituted arene) complexes with a high degree of diastereoselectivity (Y. Kondo, K. R. Green, and J. Ho, J. Org. Chem., 1993, 58, 6182).

191

MeO ~ . . Y O

Me

MeO ~ y O

Me

MeO ~ . Y O

Me

1) BuU (2.4 eq.),-30 ~ 2) e.g. M%SiCI

(OC)3Cr

(97)

I[r162-~,s

+

(OC)3Cr#

(OC~ 93:7 (86%d.e.)

The observed diastereoselectivity, which is thermodynamic in origin, reflects preferential removal of the pro-R ortho arene proton. The C2 symmetric chiral auxiliary can be hydrolyzed to afford a benzaldehyde complex without loss of optical activity. MeO~ / ~ ' O M e 0

0 '

C6H6'65%60% H2S04'~

CHO ~Me

(98)

Me

(oc)3cr~ (OCgCr4

(-) 93%e.e.

9 2 * d.e.

A similar approach has been used by the Aub6-Heppert group (J. Aub6 et al., J. Org. Chem., 1992, 57, 3563) on some chiral acetals derived from reaction of acetophenone with e!ther (S,S)-2,3-bis(methoxymethYnl 6) butanediol or enantiopure N,N,N ,N -tetramethyltartramide, followed by - i coordination using Cr(CO)6. The stereoselectivity, which increased with the Lewis basicity of the distal substituent on the dioxolane ring, again corresponds to preferential abstraction of the pro-R arene proton. XH2C4k .,,C1-12X Me3Si~

XH2C~,/~.CH2X

o

,o

1)tBuLi,-78~i=,. ~ M oe

2) Me3SiCI Cr(CO) 3

-~ (OC)3Cr

,,o

XH2C~)~.~,,CH2X o

,o

, ~ M e

i 89iMe3 (OC)3Cr

(99)

X = OMe, 82%" 78:22 (89% d.e.) X = NMe2, 62%" 94:6 (97% d.e.)

Very recently (B. A. Prise et al., J. Or g. Chem., 1994, 59, 1961) the enantioselective syntheses of some (rlt'-arene)Cr(CO)3complexes via deprotonation mediated by a non-racemic lithium amide base were reported. Hence enantiomerically enriched (rl6-arene)Cr(CO)3 complexes are now available directly via asymmetric deprotonation-electrophile quenching.

192

h•

X

1) P

" N " ~ Ph

Li

2) Me3SiCI

(oc)3cr~

X ..,~ ,,SiM~ O~

(100)

*'~

( )3Cr X = OMe, 83%, 84% e.e X = 2-(1,3-dioxolanyl), 36%, 84% e.e X = CONiPr2, 87%, 48% e.e X = CI, 27%, 51% e.e X = F, 57%, 16" e.e

(b) Structure of (Tl6-Arene) Complexes; Influence of the Cr(CO)3 Group From the highly diastereoselective or enantioselective reactions discussed above, it is obvious that there must be a high degree of specific orientation available to the transition states leading to the stereochemically-enriched substituted complexes. It has long been established that the Cr(CO)3 moiety can assume a preferred conformation in a substituted arene complex (e.g. syn-eclipsed for an electron-donating group, anti- eclipsed for an electronwithdrawing group; or staggered). Recently, X-ray analysis of a variety of complexes has established that the nature of the substituent can influence not only the preferred tripod orientation, but also that the geometry of the arene ring can alter slightly. For example, ~-donor substituents and their ipso-carbon are bent away from the Cr(CO)3 group, whereas r~-acceptor substituents and their ipso-carbon are bent slightly towards the Cr(CO)3 group in the solid state (A. D. Hunter et al., Organometallics, 1992, 11, 1550, and 2251). -

r.

.cr

.dr -

OC"" | ~CO

OC"" J ~CO

OC

~Q----~ i

OC ,,,,,.~r~co oc

Acceplor

OC

,-acceptance

~-~/~cceplor ~.

s S

o c " " *_.dr<'" | co oc

These distortions reflect electronic and not steric influences, and suggest some diminution of aromaticity in a comp]exed arene ring. In this regard NMR studies and ~:-SCF calculations on (TI6-arene)Cr(CO)3complexed benzannulenes (R. H. Mitchell et al., J. Am. Chem. Soc., 1990, 112, 7812) have led to the opposite conclusions, namely, that not only does a Cr(CO)3comp]exed ring have more bond-fixing power toward the other tings of the annulene system than benzene does, but also that the Cr(CO)3-comp]exed ring itself resists bond fixation more than benzene does. The estimate is that (1,16-__C6H6)Cr(CO)3 has ca. 1.3 times the resonance energy (i.e. is more "aromatic") than benzene. In a series of bis-Cr(CO)3-comp]exed [2,2]metacyc]ophanes the semi-quantitative correlation of the 13C NMR shifts

193

with the C-Cr (X-ray) distances underlines the importance of the orientation of the orbitals between chromium and the ligand carbons in distorted benzene rings in explaining the ubiquitous and characteristic shift of & towards higher field on complexation (J. Schulz, M. Nieger, and F. Vogtle, J. Chem. SOC.,Perkin Trans 2, 1992, 2095). In another investigation of the influence of complexation on arene reactivity, a coordinated Cr(CO)3 moiety has been compared with a nitro group with respect to base-promoted (ButOK, ButOD, 50 OC, 8h) hydrogen exchange in stilbene and 4,4'dimethoxystilbene (Z. V. Todres and E. A. Ionina, J. Organomet Chem., 1993, 453, 197). Although both the o-bound substituents and the q6coordinated group assist the exchange, for the Cr(C0)3 moiety the simultaneous presence of an electron-donor substituent (e.g. OMe) in the stilbene ligand was necessary. That is, instead of weakening the effect of a Cr(C0)3 acceptor, the OMe donor substituent strengthens it. This result is in accord with previous observations that removal of electron density from the arene ligand onto Cr(CO)3 proceeds more effectively when the arene ligand becomes a donor substituent also. Electrophilic substitution chemistry on (qhrene)Cr(CO)3complexes is not widely used. Not only are the complexes unstable towards oxidants/ electrophiles, but also the coordinated ring is expected to be deactivated towards attack of electrophiles commonly employed for SEAr reactions on the free arene. Only acylation and mercuriation are successful, and the regioselectivity of substitution differs from that in the free ligand. However, a recent study of Friedel-Crafts acetylation and H/D exchange in q6Cr(C0)3 complexes of biphenyl and diphenylmethane noted assistance to SE ( S . Rosca, F. Chiraleu, and S. I. Rosca, Rev. Roum. Chim., 1991, 36, 693; Chem. Abs. 1991, 117, 90437j). An early transition state (= a Kcomplex) was proposed for the rate-determining step; thus differing from the free arenes for which a late transition state (= a o-complex) is involved. This argument was used to rationalize the striking differences in orientation effects displayed by complexed arenes vs free arenes.

-

fc, Reactions of ($)-Arene,Cr(CO12 m lex s The major developments in the chemistry of (q -arene)Cr(C0)3 complexes since the last review in this series have been those concerned with the formation of either Carcne-Cnu~leophile/electrophileOf Cbenzylic-Cnucleo hile/ elecuo bile bonds, and cycloadditions. The electron-withdrawlng effect o the Cr(Cd)3 is manifested in enhanced susceptibility of a substituted ring towards SNAr. Moreover, the arene ring is activated not only towards attack by a nucleophile, but also towards removal of a proton. Therefore, under appropriate conditions the ring can be functionalized either by a nucleophile addition-quenching sequence, or by a deprotonation-electrophilequenching sequence. Moreover, the formation of either a carbocation or a carbanion at

F

194 a benzylic site is promoted by an q6-Cr(CO)3 moiety, thereby adding to the manifold of reactivity available to be selected and utilized in synthesis. Examples have also been reported where the influence of the rl6-Cr(CO)3 has been demonstrated at side-chain carbons further removed from the aromatic ring (for an example of remote 1,5 diastereoselection see M. Uemura, M. Tatsuya, and Y. Hayashi, J. Org. Chem., 1989, 54, 469). A review by the progenitor of many of the synthetically useful facets of 116Cr(CO)3 chemistry is available (M. F. Semmelhack, Comprehensive Organic Synthesis, 1991, 4, 517). The stereochemical aspects of the use of chiral (rl6-arene)Cr(CO)3 complexes in asymmetric synthesis have also been summarized (A. Solladie-Cavallo in Advances in Metal-Organic Chemistry, L. S. Liebeskind, Ed., JAI Press, Greenwich CT., 1989, 1, 99; A. SolladieCavallo, Trends Org. Chem., 1990, 1,237). Nucleophilic Addition to the q6-Arene Ring (i) Addition-Displacement; SNAr This sequence, which was reported in the original work of Nicholls and Whiting (1958) to demonstrate the influence of a Cr(CO)3 group on an arene ring, continues to be widely investigated and used. Detailed work by RoseMunch et al. has led to the definition of a variety of pathways which might be available to a particular nucleophile-substrate pair. A nucleophile may displace a leaving group not only via ipso attack, but also via attack at other arene carbons followed by Cr-mediated hydride shift(s), leading after aromatization to a product in which the entering nucleophile is situated either one (cine) or more (tele) carbons removed from the ipso site. The earlier work of the French group has been reviewed (J. C. Boutonnet et al., Bull. Soc. Chim. France, 1987, 640). More recent examples on monocyclic (rl6-haloarene)Cr(CO)3 substrates are also available (F. Rose-Munch et al., J. Organomet. Chem., 1989, 363, 103, 123, and 297; F. Rose-Munch, O. Bellot, and L. Mignon, J. Organomet. Chem., 1991, 402, 1). For example, primary and secondary a-sulfonyl carbanions react with (116C6H5CI)Cr(CO)3 to give, after CF3COOH treatment, aryl sulfones via ipso, cine, and tele SNAr (P. Khourzom, F. Rose-Munch and E. Rose, Tetrahedron Lett., 1990, 31, 2011 ). Cr(CO)3

C.r(CO)3

Cr(CO)3

Cr(CO)3 (101)

2) CF3COOH cJ

~ - J ~

16'/o

2 7 . '---SO2Ar

3"/o

SO2Ar

The operation of the tele pathway has also been demonstrated in polycyclic substrates (R. C. Cambie et al., J. Organomet. Chem. 1994, in press).

195

1) ~ O

OMe ~

C

CN r(CO) 3

Me02C

H

/

0

0

=

2) CF3COOH

CN

~,

MeO 2

(102)

18"; + otherproducts

The synergistic effect of a proximal Lewis base in promoting hydride attackmethoxide loss has been demonstrated (M. Persson, U. Hacksell and I. Osoregh, J. Chem Soc., Perkin Trans. 1, 1991, 1453), since reductive demethoxylation is faster in the endo complex. OMe

H

NPr2 LiAIH4( 10 eq.L

(oc)~c/

(103)

(oc)~c/ 96~176

Super-hydride can displace methoxide even from relatively electron-rich complexes (F. Rose-Munch, J. P. Dukic and E Rose, Tetrahedron Lett., 1990, 31, 2589), MeO,,~OMe

MeO~OMe LiBEI3H~c C y , ~

(OC)3Cr OMe

~OMe

r~

+

§

( )3 r OMe (OC)3Cr 73% 13% after40 ~ min

(104)

(OC)3C = 100% after2 h

and the unsubstituted intermediate q5-cyclohexadienyl anion can be isolated after being trapped with chlorotriphenylstannane (J-P. Dukic et al., J. Am. Chem. Soc., 1993, 115, 6434). H

LiBEI3H .._ 67 ~ min Cr(CO)3

U

%H

H

Ph3SnCI 53%

Cr(CO)3

U

H ._. Cr(CO)3.SnPh3

(105)

CF3COOH (OC)3Cr

(

)3C

Carbanions derived from an o~-imino ester or nitrile displace halide ions (F. Rose-Munch et al., J. Organomet. Chem., 1991, 415, 223; J. Organomet. Chem., 1990, 385, C1). Conformational studies of these complexes in solution by NMR, and of three of them by X-ray analysis, show that the nitrile or ester groups are antiperiplanar to the Cr(CO)3 moiety.

196

X

--~_I_~) R

(~:=C Ph2 THF/HMPA R " ~ ' - r t ~ Y + Li 1 _---"R 1 -78 ~ N=CPh,z y Cr(CO)3 Cr(CO)3 X = F, CI; Y = CN, CO2Me R = Me; R1 = H, Me

(106)

Optically pure or amino acids have been prepared by enantioselective substitution of (TI6-C6HsF)Cr(CO)3 using Schiff bases derived from Lalanine, L-leucine, or L-valine methyl esters and from (IR, 2R, 5R)-2hydroxypinan-3-one (M. Chaavi et al.,Tetrahedron, 1991, 47, 4619). F

Ar Ar ~::=NCH(R1)CO2Me ~C=NC(R')CO2Me R2 / C6H5 R2 LDA THF, HMPA ~ 1) H30+,air I= II ."1 ~ H2N'-'-I--COaMe or P.T.C. ~,,;'~.,,' 2) K2CO3 Cr(CO)3 10 - 76% Cr(CO)3 R1 9 - 70%

(107)

A]koxycarbony]ation of some monochloro- and dich]oro-arene complexes occurs under mild conditions in the presence of a palladium catalyst (J. F. Carpentier et al., Tetrahedron Lett., 1992, 33, 2001); for X = H or Me the yields were c a 67%. The o- and p-dichlorobenzene substrates gave essentially only monosubstitution, whereas the m e t a isomer afforded approximately equal amounts of both the mono- and di-substituted products. X ~ ~. I . CI Cr(CO)3

HCO2R/ROM~ X ~ . ] . ~ PdCI2.(PPh3)2 80 ~ 30 min

X,~_~

X,,~_ ~ l_ OR +

CO2Me +

Cr(CO)3

Cr(CO)3

H

(108)

Cr(CO)3

X = H, 4-Me, 2-CI, 3-C1, 4-C1

The substitution of halide ion in (T16-haloarene)Cr(CO)3 complexes by sulfur has been studied as a route for the thiation of aromatic tings (M. J. Dickens et al., Tetrahedron, 1991, 47, 8621). Although ipso displacement by a poorly nucleophilic heteroatom is rare, an example has been reported recently in which either amide anion or trifluoroethoxide anion react successfully with a very electron-poor p-trifluoromethylbenzene complex (F. Rose-Munch et al., J. Organomet. Chem., 1993, 456, C8). 1) NaNH2, NH3, HMPA F3C

CI Cr(CO)3

,-

F3C

2) MeOH,-78 ~

CF3CH20.Na+'~'~~ THF/HMPA F3C ~ O C H 2 C F 3 -50 ~ X=l-_/ Cr(CO)3 80%

NI-I2 + F3C Cr(CO)3

OMe Cr(CO)3

38% (109)

197 Palladium-promoted coupling has led to polymers with excellent thermal stability up to 750 ~ (M. E. Wright, Chem. Abs., 1991, 116, 4619). CI

CI ~

Ci

Cr(CO)3

Cl

=- polymer

(110)

Cr(CO)2.PBu3

(ii) Nucleophile Addition-Oxidation The susceptibility of an e x o - s u b s t i t u t e d anionic q5-cyclohexadienyl intermediate to undergo oxidative re-aromatization (by formal loss of hydride) on treatment with iodine (which also causes decomplexation) has long been recognized (M. F Semmelhack et al., J. Am. Chem. Soc., 1979, 101,3535). ~']i r(CO)3

1) Nuc" 2) 12

~

(111) Nuc

With the notable exception of those derived from sulfoxides (M. D. King, B. Kuipers and P. D. Woodgate, unpublished; but see S. Ostrowski and M. Makosza, J. Organomet. Chem., 1989, 367, 95), carbon nucleophiles derived from carbon acids with pKa __ 22 add successfully, nitrile- or ester- or 1,3dithiane-stabilized anions generally being the most widely used. Organolithiums or heteroatom nucleophiles generally do not add to arene carbon (but see later for a carboxan~de example). Regioselectivity studies have been carried out using various arene ligands. Since the Cr(CO)3 moiety is most commonly q6-bound symmetrically to the aromatic carbons (although there are cases where it is slightly displaced from central coordination) it should not exhibit any selective directing effect towards attack by a nucleophile. Hence, an extant substituent(s) should control site selectivity. For arenes bearing a single strong resonance donor (e.g. OR) meta attack by the nucleophile is strongly preferred, with small amounts of ortho attack. The regioselectivity is less for alkyl- and chloro-substituted arene complexes, for which both o and rn attack can be significant. Steric factors can influence regioselectivity; for example, -CH2CN can give appreciable amounts of products from attack ortho to a substituent, whereas-CMe'2CN gives virtually none. In a number of (q6_ methoxyarene)Cr(CO)3 complexes derived from tricyclic diterpenoids, however, -CH2CN predominantly attacked m e t a (R. C. Cambie et al., J. Organomet. Chem., 1988, 348, 317), illustrating the importance not only of substitution around the anionic carbon but also on the acceptor ring. In (q6_ benzene)Cr(CO)3 complexes, increase in the steric bulk of the existing substituent(s) disfavors ortho attack, and eventually m e t a attack also. In order to rationalize the experimentally observed regioselectivities a balance of charge control and orbital control (based on the magnitude of the LUMO

198 in the free arene ligand) is necessary to accommodate most of the data. Charge control [distribution of charge on the arene ligand induced by a preferential conformation of the Cr(CO)3 tripod] is usually limited to complexes which adopt a strongly preferred eclipsed conformation (established either by X-ray analysis for the solid state, or by an NMR approach for the solution phase; see F. Rose-Munch et al., J. Organomet. Chem., 1989, 363, 103). That is, arene carbons eclipsed by a CO ligand are expected to be more electrophilic than non-eclipsed carbons, and therefore more susceptible to nucleophilic attack under conditions of kinetic control. For example (M. Uemura et al., J. Organomet. Chem., 1991, 406, 371), 2lithio-l,3-dithiane reacts irreversibly (kinetic control; -78 ~ short time) with syn-eclipsed exo-(1-isopropyl-5-methoxy- l,2,3,4-tetrahydronaphthalene)Cr(CO)3 to give predominantly (after I2 workup) the product of attack meta to the OMe group, whereas the endo diastereomer, which has a preferred staggered conformation, affords mainly the product from ortho attack.

meta~ ,' 7% o rtho

iPr

93%

35%

meta ~~

iPr

versus65% ortho

OMe

OMe

Under conditions of" thermodynamic control (higher temperature, longer time) nitrile- or cyanohydrin-stabi]ized carbanions provide high regioselectivity for m e t a attack for both diastereomeric complexes, irrespective of the preferred conformation of the tripod. K~ndig has demonstrated that the reactions of certain nucleophiles with (1"16substituted arene)Cr(CO)3 complexes can be highly regioselective, with a product substitution pattern which is complementary to that found in classical SEAr. Indeed, the addition reaction between some nucleophilecomplex partners can be controlled to afford single stereoisomers (E. P. Kfindig et al., Helv. Chim. Acta, 1991, 74, 2007). Thus, both (l"16-1,2dihydrocyclobutabenzene)Cr(CO)3 and its indane homologue react with complete or very high regioselectivity for o~-substitution. r(CO)3

CMe2CN 1) LiMe2CN 2) 12

~

Li. s --~

(112)

86%

.Cr(CO)3

c H2C N (113)

2) 12

2)

89%

95%

In contrast, the complexes of 1,2,3,4-tetrahydronaphthalene and of 1,2dimethylbenzene give mixtures of the or- and [3-substituted products. Thermodynamic control of the product distribution was proved in several

199 cases, mixtures of intermediate anionic adducts being equilibrated to give, after oxidation, the [3-substituted derivative of tetralin or of o-xylene. The structures known for symmetrically (Tl6-o-disubstituted arene)Cr(CO)3 complexes (such as those of the four arene substrates used in this study) show them to adopt either the staggered syn conformation or the staggered anti conformation; since an eclipsed conformation is not preferred, charge control of nucleophilic addition should not be operative.

staggered syn

staggered an#

In accord with the expectation of frontier orbital control of the regiochemistry, EHMO calculations for the free ligands predict kinetic attack at the ot site for the four complexes. However, consideration of electronic effects alone does not allow prediction of the differences in regioselectivity observed in the cyclobutabenzene, indane, tetralin, and oxylene series; a steric effect also appears to be operating. Clearly, although good regiocontrol of nucleophilic addition can be obtained, careful experimentation is often necessary to define the optimum conditions. Interpretation of observed ratios of regioisomers must be based on experimentally established kinetic or thermodynamic control of the product distribution; rationalizations argued on the basis of the preferred conformation of the Cr(CO)3 tripod in the starting complex, which in any case are limited to conditions of kinetic control, may not be valid. For the addition reaction to be under kinetic control one or a combination of the following three requirements must be met: (i) temperature less than -50 ~ (ii) efficient solvation (e.g. by HMPA) of the Lewis acid cation (usually Li+); and (iii) very reactive carbanions. 2-Lithio-l,3-dithiane anions show no variation in the ratio of products derived from o, m, or p attack over the temperature range -78 to 0 ~ and their addition is therefore under kinetic control regardless of reaction temperature. Applications of this additionoxidation sequence in organic chemistry are extensive. Illustrative examples include (S. Chamberlin and S. Wulff, J. Am. Chem. Soc., 1992, 114, 10667):

9 (O

1) LDA 2) ]2 e

~" ~

OMe SPh OMe 85%

~O 0

+

Me

(114)

OMe 5%

(M. Uemura, H. Nishimura, and Y. Hayashi, Tetrahedron Lett., 1990, 31, 2319):

200

•L,•Me

~Me

_s.,

/ ~ O M ~Me e (OC)3Cr

2) 12H 50%

(115) OMeMe

(C. W. Holzapfel and F. W. H. Kruger, Aust. J. Chem., 1992, 45, 99): NHBoc

(OC)3Cr

Boc

Y

EiVL•

'COOMe

NH2

SPh

OOMe

2) 12 3) Ra-Ni 4) H+

~

(116)

~N H 31%

(R. C. Cambie et al., J. Organomet. Chem., 1994, 471,149): OMe

OMe

OyO

0

0

-.~,,~ 1) CN %Cr(CO)3 2) 92% 12

(117)

and (E. P. Kfindig et al., Organometallics, 1993, 12, 3724): Me

~ ' Q - ~ --~ " N-Nt~ (OC)3Cr enantiopure OMe

1) MeLi 2) Ph3C§ 55%

(118) = Me (OC)3Cr

>96.5

SAMP S

(OC)3Cr R

SAMP

<3.5

Prior to the latter report the exclusive reaction of an intermediate anionic adduct with electrophilic reagents (e.g. trityl cation) other than I2 was to remove the exo carbanion educt to regenerate the starting complex. The above highly diastereoselective sequence leads to (qO-o-disubstituted benzaldehyde)Cr(CO)3 complexes of high enantiomeric purity (S configuration). It is noteworthy that arene lithiation (see later) is not competitive with nucleophilic addition to the phenylmethanime (or phenyloxazoline, see later) complexes. (iii) Nucleophile Addition-Electrophile Addition As indicated previously the intermediate q5-cyclohexadienyl adduct can be induced to react with an electrophile to yield a cyclohexadiene. This disubstitution-dearomatization was demonstrated originally by Semmelhack, who found that CF3COOH was effective in protonating the anion at carbon rather than promoting reversal of the nucleophilic addition step. This

201 sequence, which provides a complementary alternative to Birch reduction/alkylation, is also effective on complexes of polycyclic substrates (R. C. Cambie et al., J. Organomet. Chem., 1994, in press), although in this case it is essential to add CF3COOH at -100 ~ to avoid regeneration of the starting complex.

o/

OMe

~

1)

MeOH2

OMe / - ~

CN

Cr(CO)3 ;i CF3COOH -100 *C MeOH2C#%,,, 60% (+ diene isomer)

-,

(119)

y

#

Li

~

Cr(CO)3

RX Cr(CO)3

J

Cr(CO)3R

,

i

Cr(CO)2L4 $ ,,

L (CO or PPh 3)

12

(120)

s

S

S .

'

_= ""C O R Cr(CO)2L2

L(C

-

R

Instead of being quenched by reaction with a proton the (1"15cyclohexadienyl) anion can react with a carbon electrophile (coupled with CO migration), leading to trans- 1,2-disubstituted cyclohexa- 1,3-dienes (E. P. Ktindig et al., Helv. Chim. Acta, 1990, 73, 386; Eq. 120)). Methyl iodide and primary iodides or primary triflates, as well as allyl bromide or benzyl bromide, were effective electrophiles. CO was preferred to PPh3 as the ligand to induce acyl migration, since the reaction was cleaner, the yields higher, and the Cr(CO)6 can be recovered and recycled. Nucleophileelectrophile double addition on (rl6-1-methoxynaphthalene)Cr(CO)3 has been used in a synthesis of the AB ring system present in aklavinone (E. P. Kfindig, M. lnage, and G. Bernadinelli, Organometallics, 1991, 10, 292). Simple alkyllithium reagents (MeLi, BuLi, PhLi, tBuLi, CH2=CHLi, LiCH2COOtBu), which normally lithiate (q6-arene)Cr(CO)3 complexes (see later), add with high regioselectivity o r t h o to an oxazoline or imine substituent (E. P. Ktindig et al., Synlett., 1991, 657). Advantage has been taken of the efficiency of this addition to trap the intermediate anion with a

202 carbon electrophile, affording (after acyl migration) a 1,5,6-trisubstituted cyclohexadiene with good stereo- and regiocontrol (E. P. Kiindig et al., J. Am. Chem. Soc. 1991, 113, 9676). N.-,, O

N.,,, O 1) MeLi 2) RX

N..,,, O +

R

N.,,,.O

§

§

R

O

.

O ~ , , . ~ ~

Orc

(OC)3Cr

N..,, O

(121) R

ca. 600/"

pot

r(CO)3

NaH/R 1Xone

As an alternative, albeit without the flexibility of the above sequence, double addition of a nucleophile can be achieved via an initial SNAr process (F. Rose-Munch, L. Mignon, and J. P. Schwarz, Tetrahedron Lett., 1991, 32, 6323). Me

. _ ~

F

1) 2 LiMe2CN, -30 ~ 5 days 2) CF3COOH, CO

Cr(CO~

CkMe2CN Me

CM~CN

9Me ~--~.__~CMe2CN

7%

(122)

40%

Arene deprotonation -Electrophile quenching The susceptibility of a complexed arene to undergo facile deprotonation continues to be utilized. A procedure in which the base and an electrophile are simultaneously present in situ has led to the regioselective hydroxylation, silylation, or carbethoxylation of the complexes of some polycyclic aromatic hydrocarbons (J. A. Morley and N. F. Woolsey, J. Org. Chem., 1992, 57, 6487). OH

* (OC

)3Or/

2) 1-1202

81%

(123) 9%

Dcprotonation-qucnching of (T16-cyc]obutabcnzcnc)Cr(CO)3affords mainly the (x-substituted arcnr (H. G. Wcy, P. Bctz, and H. Butcnschon, Chem. Bcr. 1991,124, 465). SiMe3 i] Me3SiCI

(OC)3Cr/

+ (OC)3Cr/

81%

(OC)3Cr

19%

203 One-pot difunctionalization of [2.2]metacyclophane can be effected via its bis[Cr(CO)3] complex (J. Schulz, Mnieger, and F. V6gtle, J. Chem. Soc. Perkin Trans 2, 1992, 2095). C02El

~

- c'ioI'

l'~'l----z- - Cr(CO) 3

1) 6 BuLl,TMEDA 2) CIC02Et

(125)

~Cr(CO)3 C02Et

(-)-(1S,2S)-(N,O-Dimethylephedrine)Cr(CO)3 and its (-)-(1S,2R)diastereomer undergo stereospecific removal of the pro-R ortho arene proton upon treatment with an alkyllithium reagent (S. J. Coote et al., Tetrahedron:

Asymm., 1990, 1, 817). OMe

Me

~N

,,,Me Me2

1) B u L i 2) Mel

(OC)3Cr/ (-)-(1S,2S)

OMe

~,~N,,M

e Me2

(126)

(OC)3Cr (-)-(1R,2S)

As mentioned earlier, asymmetric deprotonation followed by electrophile quenching has been used by Kondo et al. and Aub6 et al. to provide routes to enantioselectively enriched o-disubstituted complexes. Ortho lithiation of an optically active complex subtending a benzylic tertiary amine, and then reaction with an aldehyde, occurs with excellent diastereoselectivity (88-91%) (M. Uemura, R. Miyake, and Y. Hayashi, J. Chem. Soc., Chem. Commun., 1991, 1696). Me .~RN .(OC)3Cr"

Me Me2 1) R1Li [~~ NMe2 2) ROHO ~ s TM (OC)3Cr" R

(127)

Rieke has reported the scope and mechanism of the reaction of (q6.Tl6biphenyl)bislCr(CO)31 dianions with a wide variety of electrophiles (R. D. Rieke et al., Organometallics, 1992, 11,284; S. S. Yang, B. T. Dawson, and R. D. Rieke, Tetrahedron Lett., 1991, 32, 3341; R. D. Rieke et al., J. Am. Chem. Soc., 1990, 112, 8388), which give initial ipso attack exclusively, although 1,2-alkyl or-aryl migration can occur subsequently. Cr(CO)3

Cr(CO)3

COOH

RX

(OC)30r

(OC)3Cr

(OC)3Cr A

(128)

204

R=Me 1,2-Me migration

Me

A

Me +

THF, HMPA MeOTI, CO

OMe

+

Q 52%

2%

11%

Benzylic Deprotonation -Electrophile Quenching Formation and reaction of benzylic anions, stabilized by an ~6-Cr(CO)3 moiety, provides a further avenue for exploitation of the diverse reactivity of these complexes. For example, either 1,2- or 1,4-addition of an o~-lithiated complex to a carbonyl compound can be achieved (V. N. Kalinin, I. Cherepanov, and S. K. Moiseev, Mendeleev Commun., 1993, 43; V. N. Kalinin, I. A. Cherepanov, and S. K. Moiseev, Metalloorg. Khim., 1992, 5, 1356). The conjugate process occurs after transmetalation to an [TI6benzylcopper(1)] species. CHa

(OC)3Cr

CH2ki

E,Ni

CH2C(OH)Me2

M cO o%

Cr(CO)3 1) Cul ~2) CH2=CHCO2Me

(OC)3Cr U C CH2CO2H

(129)

69%XN~ Me3SiCI

Transmetalation to zinc leads to a heterobimetallic complex incorporating an T13-allylpalladium group (V. N. Kalinin et al., Mendeleev Commun., 1991, 77), which couples with iodobenzene to afford a biphenyl derivative. CH2ki

CH2ZnCI ZnCl2

Cr(CO)3

CH2Ph

[Pd('q3-CsHs)CI]2 Cr(CO)3

50%

_C H2

(OC)3Cr

~ )~ d

~

(130)

80%

Benzylic nitrosation leads to a synthesis of oximes and hydroximates (M. C. Senechal-Tocquer, D. Senechal, J. Y. Le B ihan, J. Organomet. Chem., 1992, 433, 261); the 6-methoxytetralin complex reacts at the "meta" benzylic site as a consequence of the electron-donating OMe substituent destabilizing a potential para benzylic anion. OMe [ ~

HO'N tBuOK, DMSO

OMe

[ ~ (131)

tBuONO

Cr(CO)3

63%

Cr(CO)3

205

C .2OMe

pue tBuOK. DMSO ~ tBuONO (~k=_!__.~ C,~

Cr(CO)3

85%

(132)

Cr(CO)3 "OH

Successive deprotonation-alkylation steps, both of which are regio- and stereoselective, have been employed in a synthesis of (1S,4S)-7,8dihydroxycalamenene (H. G. Schmalz et al., Tetrahedron Lett., 1993, 34, 6259). C r ~ (OC)3

BuLlHMPA OMe 1)THF, 2')'--~ "-"

OMe SiMe3 99% e.e.

95%

~r ~~ . ~ ''Me OMe I.L ~

1) SBuLi e[ r~~'c"~~M~ ~ _OMe THF, HMPA i ..~ ~'~ " Pr,'"

(OC)3Crf " ~ "OMe SiMe3

88% (OC)3

(133)

OMe SiMe3

Benzylic hydroxymethylation of chiral (o-alkoxy-, o-dia]kylamino-, or oalkyl-benzene)Cr(CO)3 substrates shows high or complete diastereose]ectivity (J. Lebibi et al., Tetrahedron, 1990, 46, 6011), allowing an enantioselective route to the decomplexed product. Me tBuOK, DMSO ~ (OC)3Cr (-)

CH20

CH2OH

~

_=~ H (OC~ r OMe (-)-s,s

CH2OH ~ H OMe (-)-R

Addition of the benzylic anion from p-(dipheny]methane)-, I~-fluorene-, or IJ.-(9,10-dihydroanthracene)-bis C r ( C O ) 3 to :~-bonded hydrocarbons (a]kene, benzene, cyclohexadienyl, cyc]oheptadieny], or cyc]oheptatrienyl) in cationic complexes of Mn, Re, Fe, Cr, Mo, W, or Co provides a synthesis of novel hydrocarbon-bridged heterometallic complexes (M. Wieser, K. Karagiosoff, and W. Beck, Chem. Ber., 1993, 126, 1081). Cr(CO)3

Cr(CO)3

[L~ (OC)3Cr

K+

~

(,3S)

(OC)3Cr M L n = Re(CO)5, Fe(CO)2C p MLn

Similarly, heterobimetallic or trimetallic complexes of Ti and Au have been prepared by addition of CpTiCl2or of Au(PPh3)C1 to a lithiated (T16arene)Cr(CO)3 substrate (P. H. van Rooyen, M. Schindehutte, and S. Lotz, Organometallics, 1992, 11, 1104). Benzylic alkylation of (rl6-methyl phenylacetate)Cr(CO)3 can be effected at a Pt cathode by electrolysis of the complex in MeCN in the presence of an alkyl bromide (A. A. Vasil'ev, V. I. Tartarinova, and V. Petrosyan, Mendeleev Commun., 1993, 27; A. A. Vasil'ev and V. A. Petrosyan, Metalloorg. Khim., 1993, 6,307).

206 Benzylic anions have also been generated via deprotonation of some (TI6allylbenzene)Cr(CO)3 complexes using tBuOK/THF or NaH/DMF or phasetransfer catalysis (M. C. Senechal-Tocquer et al., J. Organomet. Chem., 1991, 420, 185). The regioselectivity (or versus %') of trapping the anion depends not only on the carbonyl compound used as electrophile but also on the nature of the cation present. The results differ from those obtained for the non-complexed allylbenzenes, apparently reflecting steric strain in the ri6-arene. The aldol-type reaction between the benzylic anion derived from (rl6-2 ethylpyridine)Cr(CO)3 and a non-enolizable aldehyde is completely stereoselective (S. G. Davies and M. R. Shipton, Synlett., 1991, 25). .,,,,,,',~

1) LDA El (OC)3Cr

2) PhCHO or tBuCHO 3) 02

I~ ,, L N erythro

,, ,.,

~." ~. -R Me

(136)

R = Ph, tBu

Generation and Nucleophile Quenching of a Benzylic Cation It has long been established that an ri6-Cr(CO)3 moiety stabilizes not only a benzylic anion, but also a benzylic cation. Both NMR data and computational evidence indicate that a 4-(rl6-C6Hs)Cr(CO)3 substituent is electron-donating towards a pyrylium cation (B. Caro et al., Tetrahedron Lett., 1993, 34, 7259). Secondary benzylic acetates rl6-complexed by Cr(CO)3 react 100% stereoselectively with enolsilanes in the presence of ZnC12 (M. T. Reetz and M. Sauerwald. J. Organomet. Chem., 1990, 382, 121), resulting in the enantioselective ot-alkylation of a carbonyl compound by an optically active carbocation possessing planar chirality. OAc (OC)3Cr

ZnCI2 90%

(OC)3Cr

,?""~" ~"'" H ~T= O

(137) O S, optically pure

Participation by a Cr(CO)3 unit in the ionization of a benzylic alcohol with inversion of configuration to form a cationic intermediate has been demonstrated in the stereoselective cyclizations of some N-(3,4dimethoxyphenethyl) derivatives of 1-phenylethanolamines (S. J. Coote et al., Tetrahedron: Asymm., 1990, 1, 33). Subsequent trapping of the cation via SEAr occurs only on the unhindered exo face, again with inversion, resulting overall in retention of stereochemistry. The absolute configuration of the product is opposite to that obtained by cyclization of the noncomplexed starting material.

207

~ R~Cr(CO)3

y ~ R

MeO.,,,,[j~l HO" h

1) HBF,.OEI2

MeOI/~.~.~__../NMe

2) hv, O2

MeO =" ~1~ / 1 NMe MeO" ~ 75%

(138)

Treatment of an enantiopure acetal derived from an (q6-o-substituted benzaldehyde)Cr(CO)3 complex with a homoallylic alcohol in the presence of TIC14 leads enantioselectively (after decomplexation) to a cis-2-aryl-4chlorotetrahydropyran (S. G. Davies, T. J. Donohoe, and A. M. Lister, Tetrahedron: Asymm., 1991, 2, 1085, 1089). Cl ..-" M

~

CI 1) HC(OMe)3, H§ MAtO r ~ OMe 2) TiCI4, CH2=CH(CI-t2)~:~OH q'-,..~)-- CHO 3) hv, O2 (139) Cr(CO)3 (2R,3S) >g8%e.e. R

1) HC(OMe)3,H§ 2) TiCI4, EICH=CH(CH2)2OH~

3) hv, 0 2 (2S,3R,4R) >98%e.e.

I

R2....~ ~ ' 1 ]

c (col

:t

j

The mechanism proposed involves intramolecular cyclization of an intermediate O-homoallylic oxonium ion in a conformation with the benzylic H syn to the ortho substituent (OMe or Me). The relative stereochemistry between Cr(CO)3 and C2 is established by addition to the least hindered face of the benzylic cation/oxonium ion away from Cr(CO)3, that between C2 and C4 is derived from a chair transition state with ArCr(CO)3 equatorial and with antiperiplanar addition of the cation and chloride across the alkene. Pericyclic Reactions Pericyclic reactions which owe their stereoselectivity to the spatial demands placed on a transition state by a (rl6-arene)Cr(CO)3 group have received attention recently. Ktindig has provided the first example of diastereoselective cycloaddition to a transient planar chiral (oquinodimethane)Cr(CO)3 intermediate, generated under mild conditions by electrocyclic ring opening of an alkoxide (charge accelerated) and trapped in situ ( E. P. Kiindig and J. Leresche, Tetrahedron, 1993, 49, 5599).

208 OLi

-

.OAc 2.1BuLi,-78~ (ocher g

I

Li

~oc)3c/

Cr(CO&

OH R1 ',.,,"~ P"P"~_T~~..,~T ''R2R 3

OH R1 hv, 02

R4

~

R

(OC)3Cr"

(140)

R~R 2

3R2 ~.

,,~3" R4.. ! -78-0 ~

R4

R1 = CO2Me, R2 = R3 = R4 = H R 2 =CO2Me, R ] = R 3 = R 4 = H R 2 = SO2Ph, R ! = R 4 = H, R 3 = Ph

X-ray structure determination of three products showed that (anti-1tetrahydronaphthol)-Cr(CO)3 complexes are formed selectively. With esteror nitrile-substituted alkenes the major diastereomer is cis (endo addition), whereas the trans adduct (via endo addition) is largely preferred for vinyl sulfone educts. A reaction with enantiomerically pure (o~-oxy oquinodimethane)Cr(CO)3 generated from the (R,S)-syn cyclobutabenzene compl~ resulted in very high asymmetric induction (>93% e.e.). Similarly, sequential transformations of bis(alkoxides) derived from (T16-1,2dioxobe.,,zocyclobutane)Cr(CO)3 have enabled a double anionic oxy-Cope rearrangement to be carried out under mild conditions, affording a cyclopenta[a]indanone and two benzocyclooctadienones (M. Brands et al., J. Chem. Soc., Chem. Commun., 1994, 999; Eq. 141). O O Me ~ i 1' 6 CH2=O(Me)II ~ ~e - 7 8 2) H" , (141) (OC)3Cr 0)30 . Me (OC)3Cr 0 Me 48% 16% The acrylates of non-racemic (q6-1,2-disubstituted arene)Cr(CO)3 complexes with an amine and an hydroxyl group in the two benzylic positions serve as ~:-face selective auxiliaries in Lewis acid catalyzed DielsAlder cycloadditions (M. Uemura, Y. Hayashi, and Y. Hayashi, Tetrahedron: Asymm., 1993, 4, 2291; Eq. 142).

Me

I(.."T "mMe ~ O C O C H (OC)3Cr" - z. | s R

= C H 2

O Lewis ~ acid -78 ~ to rt

F COXc+ endo adducts

L/Xc= 0 ~ 0 . ~1 COXc (OC)3

4 /J (142)

(+ exo)

High endo selectivities (R = Ph, 80:20; R = 1-naphthyl or 2,4,6-C6H3Me3, > 99:1) were obtained, the diastereoselectivity in the endo adducts being

209 dependent largely on the nature of the substituent R at the carbinol stereocenter (R = aryl > alkyl) and on the Lewis acid. The conformational rigidity (essential for good stereocontrol) of an acrylate such as that where R 2,4,6-C6H3Me3 is determined by the strong electron-withdrawing ability of the Cr(CO)3 group. Chelation by the Lewis acid across NMe2 and the acrylate carbonyl imposes an s-transoid conformation on the enoate moiety. Consequently, the alkene undergoes C-C bond formations across the less shielded si face, leading to an R endo adduct. =

0.1 SnCI4,PhCH3 e

98%

(OC)3Cr I~le H i/i

~r(CO)3

Lewis acid-catalyzed hetero-Diels-Alder reactions have been investigated using (imino rlO-arene)Cr(CO)3 complexes with a non-activated alkene tethered to the 2-azadiene system (S. Laschat, R. Noe, and M. Riedel, Organometallics, 1993, 12, 3738). The tethered dienophile can attack only the face of the azadiene exo to that occupied by Cr(CO)3. Diastereoselective intramolecular cycloaddition resulted, the trans selectivity being controlled mainly by the coordinated metal, and to a minor extent by the catalyst, solvent, and substituents (Eq. 143). The cycloaddition of 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide to enantiopure Cr(CO)3-complexed styrenes proceeds with complete regioselectivity and with high stereoselectivity, affording a new route to optically active 3,5-disubstituted 4,5-dihydro-4-isoxazolines (C. Baldoli et al., Tetrahedron Lett., 1993, 34, 2529; Eq. 144). The preferred formation of the (1R, 5S) Cr(CO)3 complex requires that the nitrile oxide attacks the double bond from the face opposite that occupied by the rl6-Cr(CO)3, and that the reactive rotamer of the dipolarophile has a t r a n s o i d disposition (to minimize steric interactions). Ar Ms~R~.N

Me 70-2)~- -

(OC)3Cr/

(OC)3Cr/

~ 0

Ar M U N +

(144)

(OC)3Cr/ 98:2; 98% e.e.

Reactions at Side-chain Carbons: Remote Stereocontrol

The stereocontrol evident at the side-chain olefin in the previous example is also exemplified in many cases of diastereoselection during addition of a nucleophile to the carbonyl group of complexed benzaldehydes or acetophenones (some of which have been referred to earlier in this review). Addition of a ketone enolate to a chiral (benzaldehyde)Cr(CO)3 complex

210 occurs with complete stereocontrol (J. Brocard, L. Pelinski, and L. Maciejewski, Tetrahedron, 1990, 46, 6995), as does an ester enolate if the ortho substituent is an OMe group. Cr(CO) 3

7

cr,co,

_ z o (_ c.oc. co o so OMe

(145)

R1 R1 - H, Me, OMe

R1

Stereocontrol by a Cr(CO)3 moiety can also be manifested at sites more remote from the complexed ring. For example, some highly diastereoselective 1,2-additions of nucleophiles to an arylamine-derived imine carbon have been reported (P. B loehm et al., J. Organomet. Chem.,

1991,407, C 19). H

Nu

"~

(146)

Ph

-"-

--" Ph Cr(CO~ Nu = NaBD4, 50%; 93% d.e. Nu = MeLi, 42%; 85% d.e.

Cr(CO)3

Good diastereoselection results from reaction of the boron enolate derived from a chiral non-racemic (acetophenone)Cr(CO)3 complex with an aldehyde (M. Uemura et al., J. Org. Chem., 1992, 57, 5590; Eq. 147). Elimination of water from the aldol product affords an E enone complex; double stereoselection during conjugate addition with an optically active organocopper reagent can occur with high diastereoselectivity, again reflecting remote stereocontrol by the (rl6-arene)Cr(CO)3 unit (M. Uemura, et al., Organometallics, 1992, 11, 3705; Eq 148). Moreover, RCu.BF3 reagents gave mainly one diastereomer, while R2LiCu reagents gave mainly the epimer. O ..~oMM

O e 1) Bu2BOTI,IPr2NEI e 2") EtCHO

(OC)3Cr"

OH

s ~

El +

(OC)3Cr"

0

Me

0

(147)

8O%, 9:1

Me

Me

Me F 3 B . C u ~ O B u t

~s-OMo

R,S,R

Me

2) Ac20

8s%

'q

Me

Me

'"

(148)

3) Me~=

Cr(CO)3

Cr(CO)3

Or(CO)3

>98.5% d.e. O R

~

Me Me

LiCu@OBJ)2 86%

Cr(CO)3

O ~ ~.~s "OPri Cr(CO)3

Me Me OBut 95.5%d.e.

(149)

211 This control can be extended to 1,3,5-diastereoselection in the side-chain by conversion of the aryl ketone into a benzylic methyl substituent using the sequence shown. Rationalization of the stereochemical results for the conjugate additions is based on X-ray and NMR data, which indicate a preferred conformation for both the OMe and the enone group (anti disposed and s-cisoid), and on facially selective delivery of the alkyl group to the carbonyl and exo to Cr(CO)3. For R2CuLi, si face delivery occurs; for RCu.BF3 coordination of the aryl ketone with the Lewis acid could result in an s-transoid and anti-disposed conformer, to which re face delivery occurs. Further demonstrations that an ~6-Cr(CO)3 moiety can have both rateenhancing and steric effects at a site remote from the periphery of the complexed ring are provided by the highly diastereoselective conjugate addition of the carbanion from nitromethane to a 2-arylidene-l-tetralone complex (S. Ganesh, Tetrahedron Lett., 1991, 32, 1084), and by the exclusive endo attack during cyclopropanation of the same substrate (S. Ganesh et al., J. Chem. Soc., Chem. Commun., 1993, 224). O~ ~r(CO)3

+ Me2S=OI_ ~ Ar Bu,N.Br.,HO. 800/*

0

0 H KF, 18_crown_6 ~L .,,,~ /c H2N02 Ar CH3NO2 I1~.-"'~""T "~'~ ~ ~ A' (150) Cr(CO)3 (OC)3Cr 80-90%d.e.

The latter unprecedented example of endo selective nucleophilic addition is due presumably to initial attack of the ylide being rapid (exo) but reversible, and ring closure of the endo adduct being very fast in order to relieve unfavorable steric interactions. The non-complexed tetralone was unreactive under the conditions used. Applications in Catalysis Finally, mention must be made of the applications of (rl6-arene)Cr(CO)3 complexes as catalysts in hydrogenation and isomerization reactions (for a review of this area see M. Sodeoka and M. Shibasaki, Synthesis, 1993, 643). 4.3 (u6-Arene)M(CO)3 Complexes (M = Mo, W) In contrast to the well-developed and increasingly sophisticated use of (q6_ arene)Cr(CO)3 complexes in the synthesis of polyfunctional organic molecules, the analogous complexes of Mo and W have not been exploited. Although many (q6-arene)M(CO)3 complexes of molybdenum and tungsten have been prepared, in the main they incorporate a simple alkylarene. The broad structural and spectroscopic features, and dynamic behavior, which are characteristics of the Cr complexes, are also found in the Mo and W congeners. That is, a tripodal disposition of the carbonyl ligands around the metal is ubiquitous. However, in contrast to (q6-toluene)Cr(CO)3, (TI6-

212 toluene)Mo(CO)3 shows (X-ray) a preferred staggered orientation (D. Braga and F. Greponi, J. Chem. Soc., Dalton Trans., 1990, 3143). In general, (rl6-arene)tricarbonyl complexes of Cr are both thermally and oxidatively less stable than their Mo and W analogs. The chemistry of the Mo and W complexes is dominated by substitution at the metal (and displacement of the arene) by c~-donor ligands. Such reactions, which produce LnM(CO)3, become increasingly exothermic from Cr to Mo to W, in accord with the expected increase in bond strength going from from first to second to third row metals (S. L. Mukherjee et al., Inorg. Chem., 1992, 31, 4885). Consequently, it is not surprising that nucleophilic addition of a carbanion to the coordinated arene, followed by oxidative aromatization, has not been demonstrated for Mo and W. There is a single report of a de protonation - methylation sequence (Nail, DMF; presumably assisted bxy q~ followed by Mel treatment) at a benzylic site in T1UM(CO)3 complexes (M - Cr, Mo, W) derived from 2,4,6-trinitrotoluene (J. U. Ahmed et al., J. Bangladesh Acad. Sci., 1992, 16, 193; Chem. Abstr., 1993, 119, 8972d). Largely, however, (q6-arene)M(CO)3 (M = Mo, W) complexes have been used as catalysts for oligomerization or polymerization of alkenes (J. Astrar, Macromolecules, 1992, 25, 5150; J. S. Hamilton, J. J. Rooney, and D. G. Snowden, Makromol. Chem., 1993, 194, 2907) or alkynes (K. Tamura, M. Toshio, and T. Higashimura, Polym. Bull. (Berlin), 1993, 30, 537). 5. Other Metals

Arene-CoCp* dications have been subjected to electrochemical and EPR studies, and INDO calculations have been performed. During cyclic voltammetry, two reversible one-electron reductions were observed, and their separation is constant for a series of substituted arene complexes. Methyl substitution causes a shift of the reduction potential to more negative values, and MO calculations indicate that this is related to bonding of the ligand (U. Koelle, et al., J. Am. Chem. Soc., 1984, 106, 4152). Cyclic voltammetry studies on [(q6-hexamethylbenzene)RhCp*] 2+ show two oneelectron reductions: dication ~ monocation ~ neutral; NMR experiments suggest that the Rh(I) complex is q4 bound, thereby maintaining a 18 electron count. The corresponding iridium(III) complex undergoes a chemically reversible two-electron reduction to the Ir(I) species. The process appears to consist of two sequential one-electron reductions, but these are very close in potential (W. J. Bowyer and W. E. Geiger, J. Am. Chem. Soc., 1985, 107, 5657). The electrochemical behavior of these complexes has prompted an investigation of dimetallic cyclophane complexes. Both monoand dicobalt complexes can be prepared in good yield (Eq. 151), and have been studied using cyclic voltammetry. Electrochemistry is complicated by solvolysis, but the Cp* complexes are better behaved than the Cp ones. The

213 Co(III) complexes show two reversible reductions in their cyclic voltammograms, while the Co(II) complexes show very complex CV data, and are also paramagnetic (and not amenable to NMR study). (K.-D. Plitzko and V. Boekelheide, Organometallics, 1988, 7, 1573.) 2§

[benzeneCoCP2+][BF4"]2~(~CoCp -~___ 2(BF4")

~

Excess / [Cp'CoCI~,/ TIPF6

F

/

§

C.oCp"

CoCp*

C.oCP*2(BF 4. orPFe. ) NOPF6

,+ 2(PF6 ) CoCp" (70%)

(50%

(65%)

Arene-MCp* complexes (M = Ru, Rh, or Ir) react with hydride nucleophiles, allowing a sequence of reactions that ultimately results in the formation of cyclohexenes (S. L. Grundy and P. M. Maitlis, J. Organomet. Chem. 1984 , 272, 265; S. L. Grundy and P. M. Maitlis, J. Chem. Soc., Chem. Commun., 1982, 379). Benzene-CoCp 2+ also reacts with nucleophiles to give cyclohexadiene complexes, but the range of nucleophiles that can be used, coupled with the instability of the diene complexes, detracts from the synthetic utility of this system (Y-H Lai, W. Tam, and K. P. C. Vollhardt, J. Organomet. Chem., 1981, 216, 97). An rl2-pyridine-tantalum complex has been obtained from the reaction of pyridine with Ta(OSiBut3)3 at low temperature. Similar reaction with benzene affords a ditantalum complex in which the metals are in an unusual 1,2:4,5 anti arrangement (X-ray), contrasting with the rhenium complex shown earlier in Eq. 26. It is not possible to rule out an rl3-allyl structure for both metals because the remaining Ta-C lengths are within bonding distance (2.7]k vs 2.1-2.3A for other Ta-C distances; D. R. Neithamer et al., J. Am. Chem. Soc., 1988, 110, 4421; Eq. 153). Ta(OSiBut3)3 + pyridine

-78 "C -65%

(152) Ta(OSiBut3) 3 T.a(OSiBut3)3

Ta(OSiBut3)3 + benzene

-- ~ 0 ) ~.. - - , , j

I Ta(OSiBut3)3

(153)

214

Rh(H) (PMea) C p" hexane. 60 ~ +

- - Rh(PMe3) C p " "

(154)

Rh(H)(PMe3) C p "

0

-~

--

'-

"-

1155)

It has been postulated that the formation of 1"12 arene complexes provides a low energy path for arene C-H oxidative addition reactions; prior complexation could be followed by an intramolecular insertion process (G. W. Parshall, "Homogeneous Catalysis", John Wiley & Sons, New York, 1980, p. 123; J. Chatt and J. M. Davidson, J. Chem. Soc., 1965, 843). Investigations by Jones and co-workers have provided support for this proposal. Reaction of C5Me5Rh(PMe3)(C7D13)D with p-di-t-butylbenzene a t - 2 0 ~ results in the formation of rl2-(But2C6H4)Rh(CsMes)(PMe3), characterized by NMR spectroscopy (W. D. Jones and F. J. Feher, J. Am. Chem. Soc., 1984, 106, 1650) It was also shown that a o-bound phenylrhodium complex reacts witl~ phenanthrene at 60 ~ to give an 1"12 phenanthrene complex, character- ized crystallographically (Eq. 154), and that the same reaction with naphthalene affords an equilibrium mixture of 1"11 and 1"12 complexes (W. D. Jones and L. Dong, J. Am. Chem. Soc., 1989, 111, 8722; Eq. 155). The latter equilibrium is very sensitive to the electronic character of the naphthalene; with.2-methoxynaphthalene only the 3,4-rl complex is observed. Further demonstration of the rll-naphthyl/rl 2naphthalene equilibrium was demonstrated by NMR methods, using magnetization transfer between 31p nuclei, and it was shown conclusively that the 1] 2 complex is an intermediate during C-H activation. (S. T. Belt et al., J. Chem. Soc., Chem. Commun., 1991,266).

Second Supplements to the 2nd Edition of Rodd's Chemistry of Carbon Compounds, Vol.lll B, C,D(Partial), edited by M. Sainsbury

215

9 1995 Elsevier Science B.V. All rights reserved.

Chapter 12 NUCLEAR SUBSTITUTED BENZENOID HYDROCARBONS WITH MORE THAN ONE NITROGEN ATOM IN THE SUBSTITUENT MALCOLM SAINSBURY Introduction

Nomenclature and organisation In the chemical literature a variety of systems are used to describe the types of compounds included in this chapter. Here the system employed generally follows Chemical Abstracts since this is the primary source from which the data for the review was collected and such terms as arenediazonium, rather than aryldiazonium, are retained. Some sub-divisions of the subject matter have been made in order to provide a more readable account. Thus 1-alkyl-2-aryldiazenes are considered separately from 1,2-diaryldiazenes (azoarenes) and an attempt has been made to split the syntheses of closely related compounds such as arylhydrazines and arylhydrazones. However, to segregate the reactions of these compounds this is not a simple matter and there is much overlap. As a result all relevant sections should be consulted to provide a true reflection of progress in the area.

1. Aryinitrosamines (i) Synthesis

N-Nitroso-N,N-diphenylamine is synthesised from N-chloroformyl-N,N-diphenylamine by heating it with sodium nitrite in acetonitrile. This appears to be a general method applicable to the preparation of the N-nitroso derivatives of other secondary amines from the corresponding chloroformyl compounds (M.Nakajima and J.P.Anselme, Tetrahedron Letters, 1979, 3831). The N-nitrosation of 3,3-dialkyl-l-arylureas (ArNHCONR2) can be

216 accomplished by reacting them with sodium nitrite in formic acid at 0 ~ The products [ArN(NO)CONR z] decompose when heated to 33 ~ in argon, affording a mixture of arylisocyanates, N-nitrosodialkylamines, arylureas, and aryltriazenes (M.Tanno, S.Sueyoshi and S.Kamiya, Chem. Pharm. Bull., 1990, 38, 2644). N-Aryl-N-nitrosoacetamides [ArN(NO)Ac] are formed from the parent N-arylacetamides through reactions with dinitrogen trioxide. These products can be used to arylate alkenes in the presence of palladium bis(dibenzylideneacetone). Cycloheptene, for example, reacts with N-nitroso-N-phenylacetamide to give 3-phenylcycloheptene, but 1-octene is attacked randomly to afford a mixture of four isomeric phenyloctenes. Styrene yields a mixture of stilbene and 1,1-diphenylethene (K.Kikukawa et al., J. Org. Chem., 1985, 50, 299) (for other arylation methods and examples see sections 3, 4, 8 and 9 below). (ii) Reactions When aryl-N-nitrosoamines are heated in a mixture of hydrochloric acid and acetic acid they undergo the Fischer-Hepp rearrangement to give 4-nitrosoarylamines (S.P.Titova, A.K.Arinich and M.V.Goreelik, Zh. Org. Khim., 1986, 22, 1562).

2. Aryldiazene carbonitriles (arylazo cyanides) Aryl 1,4-bis(diazo carbonitriles) (2) form charge-transfer complexes with tetrathiofulvalenes. The former are synthesised in situ from 1,4-aminoarenes by diazotisation in the presence of sodium cyanide [S.Hiinig and T.Metzeuthin, Ger. Often., D.E. 401727 (1991); C.A., 1992, 116, 105876g]. Alternatively, 1,4-bis(N-nitrosoacetylamino)arenes (1) may be treated with trimethylsilyl cyanide (idem, Angew. Internat. Ed. Engl., 1991, 30, 563).

3. Arylazo suiphides and oxidised derivatives (i) Synthesis Arylazo sulphides (ArN=NSR), in which the SR unit is an acetylcysteine residue, are available from arenediazonium chlorides and N-acetylcysteine. The reagents are reacted together in an aqueous medium maintained at pH

217 N=NCN

N(NO)Ac

R

R

Me3SiCN iw--

N(NO)Ac

N=NCN

(1) 7-7.4 (V.I.Nifontov et al., Khim.- Farm., 1990, 24, 63).

(2)

(ii) Reactions Silver ions promote the decomposition of arylazo sulphides (4-RC6H4N=NSPh; R = Ac, Bn, or MeO) in pyridine/hydrogen fluoride to give arylfluorides (4-RC6HnF) (S.A.Haroutounian et al., J. Org. Chem., 1991, 56, 4993). The potassium salt of pentanedione reacts with (E)- or (Z)-arylazo sulphides to yield 3-arylpentanediones in modest yields (C.Dell'Erba et al., Tetrahedron, 1991, 47, 333). Similarly arylazo tbutyl sulphides (1) can be used to C-arylate other potassium enolates in dimethylsulphoxide solution. The mechanisms of the reactions are designated as SRNt dark types (idem, ibid., 1992, 48, 325; 1993, 48, 235).

Ar -- N - N - SC(Me)3 + (1)

,•R O

"K

.tBuSK

-N 2

Ar

R

O

Phenols react in much the same way and, for example, (2-cyanoaryl)azo tbutyl sulphides (2) combine with a range of phenols to afford 2-cyano-2'-hydroxybiphenyls (3) (G.Petrillo et al., Tetrahedron, 1991, 47, 9297). However, when the aryl group of the arylazo sulphide has an o-methyl substituent (see 4) indazoles (5) are produced. In this case 2-(methylidene)hydrazonocyclohexadienes may be reaction intermediates (for related work see C.Dell'Erba et al., Tetrahedron, 1994, 50, 3529).

218

X ~ [ ~

y

N=NsC(Me)3+

X

Y

DMSO. hv

CN

CN Z

(2)

(i) tBuOK

(ii) H +

(3)

X = H. Me. or MeO; Y = H. or Me; Z = H. Me. MeO. Br. NO2,CF3

N

m

N

II

R

N.SC(Me)3 (4)

R

R

H (5)

Arylazoxy aryl sulphones [ArN(O)=NSO2Ar'] plus carbon monoxide and a palladium catalyst, tetrakis(triphenylphosphine)palladium, yield benzoic acids and minor amounts of biaryls and diaryl ketones. If alcohols are added esters form, and with amines amides are produced. It seems that both aryl groups of the sulphones can be transferred and the reactions involve catalytic cycles in which diarylpalladium(II) species may participate (N.Kamigata et al., Sulphur Letters, 1990, 11, 177; J. Chem. Soc., Perkin 1, 1990, 549). In an extension of this work it has been shown that the same reagent combination serves to arylate tx,~-unsaturated esters and nitriles. Thus ethyl cinnamate is obtained from a reaction between ethyl acrylate and phenylazoxy phenyl sulphone (N.Kamigata, M.Satoh and T.Fukushima, Bull. Chem. Soc., Japan, 1990, 63, 2118). In yet another example, Kamigata et al. (Chem. Letters, 1987, 347) have demonstrated that aryl arylazo sulphones (ArN=NSO2Ar') can be used to arylate styrenes in the presence of tetrakis(triphenylphosphine) in benzene solution at 80 ~ Unfortunately these last reactions are unselective and a complex mixture of stilbenes and arylstyrenes is formed, together with aryl 2-(arylazo)-2-(phenyl)ethyl sulphones [PhCH(N=NAr)CH2SO2Ar' ]. In a similar procedure aryl arylazo sulphones can be reacted with norbom-

219 ene to afford norbomane-fused 2,3-dihydrobenzothiophene 1,1,-dioxides (N.Kamigata et al., Phospor. Sulphur Silicon., 1992, 69, 129).

Ph

"N~

N

+

~

Pd(PPh3)4,_

C oS.o

"~

"S02Ph

4. 2-Alkyl-l-aryldiazenes (arylazoalkanes), (arylazoalkenes) and related compounds

2-alkenyl- 1-aryldiazenes

(i) Synthesis 2-Alkyl-l-phenyldiazenes (PhN=NR, R = alkyl) are synthesised through the reactions of alkylamines (RNH2) with nitrosobenzene. Other products include azoxybenzene and a trace of aniline. Previously reactions of this type were considered unlikely. (Y.M.Wu, L.Y.Ho and C.H.Cheng, J. Org. Chem., 1985, 50, 392). Aryldiazenes are also formed by reacting acetanilides with nitrobenzenes in xylene with powdered sodium hydroxide, potassium carbonate and a phase transfer catalyst at 130 ~ Nitrosobenzenes, rather than nitrobenzenes, are assumed to be the reactive species leading to 1-acyl-l-arylhydrazine 2-oxides as intermediates (N.R.Ayyanger, S.N.Naik and K.V.Srinivasan, Tetrahedron Letters, 1989, 30, 7253). 0

O" ~Me

Ar -" N "

H

/~Me

B ~ -BH+

N \

O~ /

Ar "

N - N .. R Ar

N -N /

OP

~1~ Ar

MeCO2"-

RNO

t

220 Alkyl radicals couple with arenediazonium salts in the presence of metal ions (Ti3§ or Fe 2+) to give 2-alkyl-l-aryldiazenes. The reactions may proceed as follows, but appear to be highly sensitive to polar effects (A.Gitterio and F.Minisci, J. Org. Chem., 1982, 47, 1759; 1992, 57, 3929): ArN2 + + Ti(IIl) --* Ar" + N 2 + Ti(IV) At" + RI --> Arl + R" R ~+ N-N+Ar ~ R_N=N+*_Ar R-N=N+'-Ar + Ti(III) --~ R-N=N-Ar + Ti(IV) (R = primary, secondary, or tertiary alkyl, alkenyl, benzyl etc., Ar = 4-C1C6H4).

Phenylhydrazones of alkanals (PhNHN=CHCHR2) are converted into 2-alkenyl-l-phenyldiazenes (PhN=NCH=CR2) either by reaction with iodine and pyridine, followed by elimination of pyridinium iodide, or from (Na-tosyl)phenylhydrazones [PhN(tosyl)N=CHCHR 2] by treatment with potassium tbutoxide and elimination of toluenesulphinic acid. Both routes give configurationally mixed products, although the E,E-isomers are thermodynamically most stable (J.G.Schantl and T.Hebeisen, Tetrahedron, 1990, 46, 395). Acetone 4-chlorophenylhydrazone (4-C1-C6H4NHN=CMe2) reacts with bromine/acetamide to give 2-(2-bromoprop-2-yl)-l-(4-chlorophenyl)diazene [4-C1-C6H4N=NC(Br)Me2], which is unstable, and 2,2-bis[1-(4-chlorophenyl)azo]propane [(4-C1-C6H4N=N)2CMe2]. The fin'st product reacts with a wide range of nucleophiles which displace the bromine atom as bromide ion giving the corresponding derivatives [4-C1-C6H4N=NC(R)Me2; R - CN, 2-phthalimido, 4-morpholino, AcO, EtO, HS etc.] (J.G.Schantl and H.Gstach, Monatsh. Chem., 1985, 116, 1329). Catechol (1,2-hydroxybenzene) reacts with benzene diazonium chloride to give a mixture of 4- and 5-(phenylazo)-2,4-cyclohexadien-l-ones, the latter predominating (A.A.Matnishyan and A.M.Arzumanyan, Arm. Khim. Zhur., 1991, 44, 469; CA., 1992, 117, 191403a). (ii) Reactions Alcohols (ROH) undergo 1,4-additions to the diazadiene system of 1-phenyl-2-(1,2-diphenylethenyl)diazene in the presence of copper(H) and iron(II) cations. The products, phenylhydrazones of ct-alkoxybenzyl phenyl ketones, are normally formed in 90-95% yield (O.Attanasi, P.Battistoni and G.Fava, J. Org. Chem., 1981, 46, 447).

221

Ph '~1

Ph

ROH

H Ph

Cu2+/Fe2+

~N=-~k Ph

1H-4,5-Dihydro-l,3,4-benzotriazepines are formed when 1-aryl-2-iminodiazenes are heated. Probably the reactions proceed through initial isomerisation of the starting materials to give ortho-quinonoid tautomers, followed by intramolecular nucleophilic attack which regenerates the aromaticity of the benzenoid ring in the products (R.Fusca, A.Marchesini and F.Sannicolb, J. Het. Chem., 1986, 23, 1795). R1 A

N--~NAr

R~ ~1 R

"H

R

1

/N N~H R Ar

y

R~'e,-~ " ~

N,,Ar

R

Essentially the same type of process is implicated in the cyclisation of 1-(2-methylphenyl)diazenes (1; R= CONH 2, CO2Et, or COPh) to the corresponding indazoles in the presence of DBCO (idem, ibid., 1987, 24, 773).

--R ~

N ~ / \H

--R

(1) 1-Arylazo-2,2-dichloroethenes react with amines by addition/elimination

222 to afford the corresponding 1-arylazo-2,2-bis(diamino)ethenes. When the starting compounds are treated with benzene-1,2-dithiol benzo-1,3-dithioles (2) are produced (T.L.Gilchrist, J.A.Stevens and B.Parton, J. Chem. Soc., Perkin Trans.1, 1985, 1737). CI

H

R2NH

CI

N=NAr

R2'"~_~' ~" u' /

SH

R2N

\

N=NAr

s

H

S

N=NAr

(2) Treatment of 6-amino-5-(1-aryldiazen-2-yl)-l,3-dimethyluracils with ethyl propiolate gives Michael type adducts (3), which on treatment with a mixture of hydrochloric and acetic acids undergo acid catalysed rearrangements and cyclisations to form 8-(N-arylaminomethyl)theophyllines (4) (F.Yoneda and R.Koga, J. Het. Chem., 1982, 19, 813). 0

0

J.L O

N~ I

I

Me

(,3)

H

ii

H

CO2Et

_

I~ CH2NHAr

O

N I

Me

(4)

Other similar cyclisations are noted in reactions between 5-phenylazo-6-arylidene)hydrazino-l,3-dimethyluracils (5) and dimethylformamide dimethylacetal which afford pyrimido-l,2,4-triazines (6)

223 (S.Nishigaki et al., J. Het. Chem., 1982, 19, 769).

Me.Ij.EL . O

O

Me

I

Me

N

~

R

oL .o'

N"

I

,, L

I

H

Me

(6)

(5)

5. Aryldiazene oxides Synthesis

1-Aryl-2-bromodiazene 1-oxides [ArN(O)=NBr] are prepared by reacting nitrosobromides with nitrogen tribromide, generated in situ from ammonia and N-bromosuccinimide (A.M.Churakov et al., Ivz. Akad. Nauk. SSSR., Ser. Khim., 1990, 953). They react with terminal alkenes (CH2=CHR) to form 1-aryl-2-bromoethyldiazene 1-oxides [e.g. ArN(O)=NCH2CH(Br)R] (A.M.Churakov et al., Mendeleev. Commun., 1991, 141). 1,2,3,4-Tetrazine-l,3-oxides (2) are formed when 1-(2-aminophenyl)-2-tbutyldiazene 1-oxides (1) are treated with nitrosofluoroborate in acetonitrile, and the products are oxidised by exposure to 3-chloroperbenzoic acid (A.M.Churakov et al., lvz. Akad. Nauk. SSSR., Ser. Khim., 1990, 718; for similar reactions see A.M.Churakov, S.L.Ioffe, and V.A.Tarakovskii, Mendeleev. Commun., 1991, 101).

OI

[~

N+"N- C(Me)3 NH2 (i)

0I

~N+" N I+ ~ [ ~ J ~ N~.N-o -

(2)

224 6. Azoarenes (1,2-diaryldiazenes) (i) Synthesis Azoarenes are frequently synthesised by coupling reactions between electron-rich arenes and arenediazonium salts (also see section 8). In addition, the trialkylstannyl unit is an excellent leaving group and this can be exploited in formation of azoarenes. Thus various trialkylstannylarenes (R3SnC6H4R'; R = Me, or Bu) when treated with nitrobenzenediazonium tetrafluoroborates [2,4-X(NO2)C6H3N2BF4] !n acetoniwile solution at 20 ~ afford the corresponding azobenzenes [R C6H4N=NC6H3(NO2)X-4,2 ). Yields can exceed 80% (W.P.Neumann and C.Wicenec, Chem. Ber., 1991, 124, 2297). The oxidative coupling of aryliminodimagnesium bromides to afford symmetrical azobenzenes is promoted by the addition of copper(II) chloride, whereas condensations with nitrobenzenes to produce azoxybenzenes are improved if nickel(II), or cadmium(H) chlorides are added to the reaction mixtures (M.Okubo and H.Shiku, Bull. Chem. Soc., Japan, 1991, 64, 196; for related work see M.Okubo et al., ibid., 1983, 56, 199). Symmetrical azoarenes are also obtained by the cathodic reduction of aromatic nitro compounds in an undivided cell. The reductions are best carded out in alkaline methanol at constant current. In this way 2,2'-dimethylazobenzene can be prepared from 2-methylnitrobenzene in 95% yield (H.Tanaka, Y.Murami, and S.Torii, Chem. Express, 1989, 4, 531). Arylamines are oxidised by chromyl chloride (C.rO2C12) in carbon tetrachloride, or in chloroform, solution to yield Etard adducts. The products upon hydrolysis give azobenzenes, plus 1,4-benzoquinones, for example, 4-chloroaniline affords 4,4'-dichloroazobenzene, the iminobenzoquinone (7) and the imines (8) and (9) (C.Naillaiah and J.A.Strickson, Tetrahedron, 1986, 42, 4083). Bipyridylsilver permanganate is an effective oxidant for the conversion of 3-nitroaniline into 3,3'-dinitroazobenzene (H.Firouzabadi, B.Vessal and M.Naderi, Tetrahedron Letters, 1982, 23, 1847). Alternatively, potassium permanganate in benzene-water containg the phase-transfer agent tetrabutylammonium bromide is recommended (M.Heyayatullah and A.Roger, Bull. Soc. Chim., Belg., 1993, 102, 59).

225

O

"CL CI

O

CI 84 (8)

(7) CIl.~

N/ H

(9) Arenediazonium chlorides (ArN2C1) couple with 1,3-diaminobenzene at the ortho positions to afford tris(arylazo)diamines (10), whereas with diethylphenylamine para-coupling occurs to give azobenzenes (11) (Z.V.Stepanova, P.I.Grebneva and G.G.Skvortsova, Zh. Org. Khim., 1982,

18, 1711). The oxidation of anilines, using either superoxide ion in the presence of 18-crown-6 ether in dry benzene, or molecular oxygen in the presence of hydroxide ion, gives a mixture of the corresponding nitrosobenzene, nitrobenzene, and azobenzene in a constant molar ratio of (19:19:13). Aniline and hydrazobenzene both afford azobenzene in almost quantitative yield under these conditions: a result which suggests that hydrazobenzene, formed by the coupling of aniline, may be the precursor of azobenzene (E.B.-Hergovich, G.Speier and E.Winkelmann, Tetrahedron Letters, 1979, 3541). The major products from the irradiation of aniline in dichloromethane, chloroform, or carbon tetrachloride, with ultraviolet light are" azobenzene, hydrazobenzene, phenylisocyanide, 2- and 4-(phenylamino)anilines, N-(methylidene)aniline (PhN=CH2) and di(N-phenylamino)methylimine [(PhNH)2C=NH] (W.Bosyczyk and T.Latowski, Z. Naturforsch. B, Chem. Sci., 1989, 44, 1585; 1589).

226

ArN=N

NH2

NH2

ArN2CI \

N=NAr ArN=N

NH2

NH2

(~o)

~ ~ INEt2

i NEt2

ArN2CI v

ArN=N

(11) (Ar = 4-CH2=CHOC6H4)

N-[(Diphenylphosphinyl)oxy]arylamines [ArNHOP(O)Ph2] combine with N-methylaniline to give hydrazo compounds [ArNHN(Me)Ph], however, in the preence of a secondary aliphatic amine, such as dipropylamine, symmetrical azoaryls (ArN=NAr) are formed (G.Boche, C.Meier and W.Kleemiss, Tetrahedron Letters, 1988, 29, 1777). In related work hydroxamic acid derivatives (4-RC6H4N(OAc)OSOEMe) combine with butylamine to give azepines (12) as well as azoarenes (13) (F.Bosold, G.Boche and W.Kleemiss, ibid., p.1781). It is argued that the initial step in these last reactions is the formation of a singlet nitrene. The nitrene may then either undergo inter-systems crossing to afford a triplet which then gives the azoarene, or combine directly with butylamine to yield the azepine.

, ~ N

NHBu

(13)

(12) (R = NO2, COMe, CO2Me,CN)

227 The dianion of 1,4-dinitrocyclooctatetrene reacts with arenediazonium tetrafluoroborates to displace one of the nitro groups and to form 1-arylazo-4-nitrooctatetraenes (Z.V.Todres and G.Ts.Ovsepyan, Ivz. Akad. Nauk. SSSR., Ser. Khim., 1985, 2830).

O2N~

NO2

ArN2BF4.._._ THF/-10 to-50~

O2N " ~

N=NAr

In reactions with the dianion of 1,2-dinitrobenzene similar results are observed and 1-aryl-2-(2-nitrophenyl)diazenes are produced (Z.V.Todres, G.Ts.Ovsepyan and E.A.Ionina, Tetrahedron, 1988, 44, 5199). Perchloroazobenzene and 2,2',3,3',5,5",6,6'-octachloroazobenzene (16) have been synthesised from 1,4-diamino-2,3,5,6-tetrachlorobenzene. The common precursor is the 1,4-iminoquinone salt (14), formed from the diamine by treatment with chlorine and iodine in carbon tetrachloride. When this salt is treated with methanol 4,4-diamino-2,2',3,3',5,5',6,6'-octachloroazobenzene (15) is produced, this compound can be deaminated to give the octachloro derivative (17) by diazotisation and treatment with methanol, or be subjected to a Sandmeyer chlorodeamination reaction to afford the perchloro derivative (16) (M.Ballesteros et al., Tetrahedron Letters, 1980, 21, 4119). Solid benzenediazonium sulphate suspended in hexane reacts with sodium diethyl malonate to give the phenylhydrazone (18) of diethyl 2-formylmalonate, and the diazenes (19), (20), and (21) (M.U.Ahmad et al., J. Bangladesh Chem. Soc., 1990, 2, 33). CI

CI

H2N

Cl NH2

CI

CI

~

CI

HN

NH2 CI

CI (14)

CI21-

228 CI

CI

N I~"

MeOH H2N CI

NH2

CI

(15)

C'

CI

C'

_ ~

C'

N 4'

c~

C'__

Cl CI

CI

Cl

Cl

CI

CI

N 4'

CI

CI

CI

CI

(16)

(17)

[2.2] (4,4')Azobenzenophane 4,4'-dinitrobibenzyl. The two deformed from planarity both (N.Tamooki et al., Tetrahedron,

is formed by the reduction of azobenzene units of this compound are in the crystalline state and in solution 1990, 46, 5931).

NO2 I

LAH

N--N

=

N--N

NO2

CI

229 R i

H I

N_N

(CO2Et) 2

(18)

(19)

R

N" PhN=N

PhN=N

N -R (21)

(20) R = Biphenyl

(ii) Reactions (a) Reduction \ cyclisation Azoarenes are reduced to hydrazobenzenes, in good yield by reacting them with tributyltin hydride in boiling benzene. However, if the azobenzene is substituted in the ortho-position then cyclisation to a heterocycle may occur as a competitive process. For example, 1-(2-acylphenyl)-2-aryldiazenes (1) form indazoles (2), and 2,2'-dicyanoazobenzene (3) affords l l-aminoisoquinolino[4,3-b]indazole (4). These reactions do not normally require the presence of an initiator, but the addition of AIBN is necessary to effect the cyclisation of 2'-iodo-2-[Na-(4-methylphenylazo)]biphenyl (5) to N-(4-methylphenylamino)carbazole (6). This product is accompanied by 2'-iodo-2-[Np-(4-methylphenyl)hydrazino]biphenyl (7) (A.Albertini et al., J.

230

Org. Chem., 1992, 57, 607). R

[~

Bu4Sn

COR

N - Ar

v

N=NAr

(1)

(2)

NH 2 N.... CN

N- N

Bu4Sn

CN

(4)

(3)

Bu4Sn/AIBN I

Ar = 4-CH3C6H4

(6)

(5)

C

NHAr

NHNHAr

(7) (1,2,3-Benzotriazol-2-yl)phenols can be formed through the cyclisation of 2-[(2-nitrophenyl)azo]phenols with thiourea-S,S-dioxide (S.Tanimoto and T.Kamano, Synthesis, 1986, 647).

231

R HO

R

NH2CS(O)2NH2

II

N

N'

R [ ~ NO2

R

2-Arylcinnolines are available by the cyclodehydration of 2-(arylazo)phenylacetic acids by the action of oxalyl chloride (M.G.Hutchings and D.D.Devonald, Tetrahedron Letters, 1989, 30, 3715).

"•••

CO2H CIOCCOCIR , ~ ~ ~ ~ N'Ar

NO N" "Ar

(b) Reactions with carbenes Azoarenes react with carbenes to form 2-arylindazoles, but it is uncertain whether these reactions proceed through ylide intermediates, or by concerted cycloadditions (K.Krageloh, G.H.Anderson and P.J.Stang, J. Amer. Chem. Soc., 1984, 106, 6015). R

.~N

II

In view of this it is

:CXY

.~

N

R

surprising that azobenzene reacts with

232 dichlorocarbene, generated from chloroform by treatment with potassium hydroxide under phase-transfer conditions, to give N-phenyltetrachloroaziridine (8) plus smaller amounts of 2-chloro-l-phenylbenzimidazole (9) and 1-phenylbenzimidazol-2(3H)-one (10) (T.Fujiu, K.Izumi and S.Sekiguchi, Bull. Chem. Soc., Japan, 1985, 58, 1055). Ph i

Ph

o o, CI

Ph i

o,

CI (8)

(9)

(10)

H

(c) Isomerisation The thermal equilibrium of cis and trans-azobenzenes in solution normally favours the trans forms. Access to the cis isomers can be effected by photoexcitation, but in the dark such isomers undergo thermal relaxation back to the trans forms. However, for certain azobenzenes beating a 4-(N,N-dimethylamino) substituent the relaxation process is strongly inhibited by the presence of hydroxide anion (A.Sanchez and R.H.Rossi, J. Org. Chem., 1993, 54, 2094).

7. Azoxyarenes (1,2-diaryldiazene N-oxides) (i) Synthesis Nitrobenzenes can be reduced by sodium hydride and cadmium(II) chloride to afford azoxyarenes, whereas if the reductant is zinc(H) chloride the products are azoarenes (G.Feghouli et al., J. Chem. Soc., Perkin Trans.1, 1989, 2069). An alternative method is to use sodium borohydride in alkaline ethanol containing a catalytic amount of diphenyl ditelluride. In this case the active reductant is sodium benzenetellurolate and azoxyarenes are formed selectively in good to high yields (K.Ohe et al., J. Chem. Soc., Chem. Commun., 1988, 591). Electrochemical reduction of nitroarenes in acetonitrile at a mercury pool cathode can also be used to prepare azoxyarenes. Here the reactions are promoted if carbon dioxide is present and a proton source is unnecessary (T.Ohba et al., J. Chem. Soc., Chem. Commun., 1994, 263). Arylamines can be oxidised to azoxyarenes by a variety of oxidants,

233 however, most methods are not catalytic. An exception employs dilute aqueous hydrogen peroxide in boiling acetone over a TS-1 zeolite (H.R.Sonawane et al., J. Chem. Soc., Chem. Commun., 1994, 1215). Oxidation of 2,6-dimethylaniline with hydrogen peroxide/sodium tungstate gives 2,2',6,6'-tetramethylazobenzene dioxide (1). Reduction of this product with hexachlorodisilane in chloroform gives 2,2',6,6'-tetramethylazobenzene (2) (J.C.Stowell and C.M.Lau, J. Org. Chem., 1986, 51, 1614).

+OI1+

Si2CI 6

lb...

/

0-" N ~ ~ }

CHCI3

(1)

(2)

Certain 4,4'-dialkylazoxybenzenes, such as (3), show liquid crystalline properties. Compound (3) is synthesised from 4-pentylaniline as shown in scheme 1 [J.P., 60 32 757 (1985); C.A., 1985, 103, 71042w]"

CH3(CH2)4~

4-NH2C6H4Pr

EtMgBr

NH2

CH3(CH2)4

CH3(CH2)4

/

N(MgBr)2

O-

N+

v

Pr

02

(3) Scheme 1

The thermolysis of zwitterionic 2-nitro-N-(pyrid-l-yl)anilines (4) gives 1,2-bis[(Z)-(2-nitrophenyl)-O,N,N-azoxy]benzenes (5), not tris(N-2-nitrophenyl)triaziridines as previously thought (H.Hilpert, L.Hoesch and

234 A.S.Dreiding, Helv. Chim. Acta, 1981, 64, 2095). ~

O2N~

R

\ +

A O2N

i,~'~ N,,-N

(R = H,Me,Cl)

(4)

O2N ~_~.~jN.R (5)

(ii) Reactions (a) Reduction Azobenzene and azoxybenzene can be reduced by dihydrolipoamide in the presence of Fe 2§ to give hydrazobenzene, without the co-production of aniline (M.Kijima et al., J. Org. Chem., 1983, 48, 2407). Anilines are formed from azoxybenzenes if the reductants are sodium alkylthiolates (M.T.Dario et al., Tetrahedron Letters, 1994, 35, 301). This is unusual, since the reaction conditions (heating in propanol) are non-acidic, suggesting that the initial step is the formation of nitrosoarenes and sulphenamides. The former are recycled, but the latter are reduced to anilines"

RSNa Ar .N;N(O)Ar T

RS-

Ar.NO + Ar.NHSR PrOH

~ [H]

Ar.NH2

A

2,2'-Dimethylazoxybenzene undergoes nitration to afford 2,2'-dimethyl-4'-nitroazoxybenzene, which can be reduced with stannous chloride to give 2-methylaniline and 2-methyl-l,4-diaminobenzene (6). In addition, the unexpected product 4,4'-diamino-3,3'-dimethylbiphenyl (7) is obtained

235 (J.Urbanski and I.Wolak, Polish J. Chem., 1984, 58, 1035). Me

H2N ~

Me

NH2 (6)

Me

H2N ~

NH2 (7)

(b) Rearrangements The mechanism of the Wallach rearrangement has been reviewed (G.G.Furin, Usp. Khim., 1987, 56, 911). Generally the acid promoted rearrangements of 4,4'-disubstituted azoxybenzenes give 2-hydroxyarylazo compounds, however, when 4,4'-dimethylazoxybenzene is heated with aluminium trichloride in nitromethane for four hours at 100 ~ it yields 3-chloro-4,4'-dimethylazobenzene (14%), 4-chloromethyl-4'-methylazobenzene (21%), and 4,4'-dimethylazobenzene (30%). 4-Methylazoxybenzene (a mixture of N~(O) and N(O)~ isomers) affords 3-chloro-4-methylazobenzene, 4-chloromethylazobenzene, 4-chloro-4'-methylazobenzene, and 4-methylazobenzene. Similar chemistry is noted for other azoxyarenes (I.Shimao, Nippon Kaguku Kaishi, 1984, 2009; 1985, 1556; see also J.Yamamoto et al., ibid., 1987, 851). Azoxybenzenes give a 1:1 addition complexes when treated with antimony pentachloride in carbon tetrachloride. These complexes also undergo ortho-Wallach rearrangements when heated in an inert solvent to form o-hydroxyazobenzenes (J.Yamamoto, Y.Nishigaki and M.Umezu, Tetrahedron, 1980, 36, 3177). (c) Uses in heterocyclic synthesis The cyclisation reactions of N~l,(O)-o-(propanoyl)azoxybenzene (1) has been studied. In the presence of sodium methoxide and methanol a mixture of 1,2,3,4-tetrahydro-3-methoxy-3-methyl-2-phenylbenzopyridazin-4-one (2), bis(2-methylindolin-3(1H)-on-2-yl) (3), and azoxybenzene are formed (S.S.Mochalov, A.N.Fedotov and Yu.S.Shabarov, Khim. Geterot. Soedin., 1983, 688; 743).

236 O COEt

NaOMe/MeOH ~1'~...i'~ N .. N -. ph

II

I

H

o--N+ph

(2)

(1) O

~ _ ~ M

e

H N

(3)

8. Arenediazonium salts (i) Synthesis 1-Aryl-2-(piperid-l-yl)diazenes can be used as a source of diazonium salts. On treatment with methanesulphonic acid in organic solvents these compounds dissociate into the corresponding arenediazonium methanesulphonates and piperidine (T.J.Tewson and M.J.Welch, J. Chem. Soc., Chem. Commum., 1979, 1149). Similarly, 1-aryl-3-(tetrazol-5-yl)triazenes cleave when reacted with trifluoroacetic acid giving arenediazonium salts and 5-aminotetrazole. As such the parent compounds act as bench stable arenediazonium synthons and, for example, may be used to couple with phenols affording azo compounds. Alternatively they may be reacted with ammonium halides and trifluoroacetic acid to give halogenoarenes. It seems that radicals are not involved in these reactions (R.N.Butler and P.D.O'Shea, J. Chem. Soc., Perkin Trans. 1, 1987, 1039). Another convenient source of the benzenediazonium cation is from azobenzene-t~-hydroperoxide (T.Tezuka, S.Ando and T.Wada, Chem. Letters, 1986, 1667). Nitrodiazophenols (3) are prepared by the nitration of suitable anilines and the rearrangement of the product N,C-nitroamines (1). The rearrangement reactions are considered to involve 1,2,3-benzoxadiazoles (2) as intermediates (R.L.Atkins and W.S.Wilson, J. Org. Chem., 1986, 51,

237 2572).

O

H

_

H tO "N +. N

I

"N"

N+

<'0

_

/

O-H

N-N

R~ N O 2

02

NO2

Rv

NO2

"NO 2

(1)

N2+

N "" N

-NO2+

O--.------I~

-HO02

NO2 (3)

(2)

1- [4- (N-Chloroformyl-N-methylamino)phenyl]-2-(phenylsulphonyl)diazenes (4) are described as bifunctional reagents containing a protected diazonium group. With amines they afford the corresponding ureas (5) and when these are reacted with aqueous methanol in tetrahydrofuran, followed by ion exchange over Dowex-Cl-, the diazonium chlorides (6) are produced (P.Kessler et al., Synthesis, 1990, 1065).

o

O .

CI~ " N

R2N

I

N I

Me

Me

(4)

(5)

N=NSO2Ph

238

MeOH/H20

R2NL N~

Dowex-CI-

N2CI

I

Me (6)

An unsual reaction occurs when the amino(hydroxyethoxy)terephthalate ester (7) is diazotised with nitrous acid in the presence of nickel(II) cyanide. It seems that the diazonium salt (8) is initially formed, but it then undergoes irreversible intramolecular cyclisation to the stable quinone diazide (9) (C.A.Panetta, Z.Fang and N.E.Heimer, J. Org. Chem. 1993, 58, 6146).

CO2Me CH2CH2OHHNo2

CO2Me CH2CH2OH

CO2Me O ~)"~

-------tP,-

H2N

Ni(CN)2 X2N COeMe

CO2Me

(7)

(8)

N~. -

(

CO2Me (9)

(ii) Reactions The reactions of arenediazonium salts have been surveyed (K.Fukunishi and M.Nomura, Senryo Yakuhin, 1986, 31, 120). The complexation of arenediazonium ions by multidentate ligands has also been reviewed (R.A.Bartsch, Prog. Macrocyclic Chem., 1981, 2, 1) and various coupling interactions between diazonium salts and active methylene compounds have been investigated and summarised (N.Prasad and A.Sahay, Asia J. Chem. Reviews, 1993, 4, 23; A.Sahay, ibid., 33). (a) Arylation Quaternary salts and carboxylate anions in benzene, containing acetonitrile as co-solvent, mediate the Gomberg-Bachmann arylation reactions of arenediazonium tetrafluoroborates which lead to biaryls

239 (D.E.Rosenberg et al., Tetrahedron Letters, 1980, 21, 4141). Pyruvaldehyde oxime (MeCOCH=NOH) can be phenylated by benzenediazonium chloride to afford the oxime of 1-phenylpropane-l,2-dione [MeCOC(Ph)=NOH] (K.Kanungo et al., Vijnana Parishad, Anusandhan Patrika, 1980, 23, 295). Camphene (7) is arylated by arenediazonium tetrafluoroborates in the presence of palladium(II) acetate at 30-50 ~ in ethanol solution. The products undergo E/Z equilibration on exposure to ultraviolet light (Y.Wang et al., Synthesis, 1991, 967).

~~, F4

Pd(OAc)2

AF h~

~1~

Ar

~

(7) It is usual to employ palladium based catalysts to initiate the arylation of alkenes with arenediazonium tetrafluoroborates, and much work in this area has been reported by Kikukawa and colleagues. Thus the phenylation of ethene is carded out using benzenediazonium tetrafluoroborate in the presence of bis(dibenzylidene acetone)palladium and sodium acetate in a 1:1 mixture of acetone and dichloromethane. This gives styrene in ca 70% yield (K.Kikukawa et al., Bull. Chem. Soc., Japan., 1979, 52, 2609). Arenediazonium tetrafluoroborates can be used to displace the silyl substituent from 2,3-dimethyl-l-trimethylsilylbut-2-ene. Thus a reaction with 2,4-dinitrobenzene-diazonium tetrafluoroborate affords 2,4-dinitro-(2,3-dimethylbut-l-en-3-yl)benzene (H.Mayr and K.Grimm., J. Org. Chem., 1992, 57, 1057).

Me

O2N

Me

Me~

Me SiMe 3

02N

The 0~-arylation of ketones can be effected by reacting silyl enol ethers

240 with arenediazonium tetrafluoroborates in the presence of palladium(0) catalysts and tetraphenylborate anion. Alternatively, the ethers can be reacted with arenediazonium tetrafluoroborates in contact with pyridine, this procedure does not require catalysis (T.Sakakura, M.Hara and M.Tanaka, J. Chem. Soc., Perkin Trans 1, 1994, 283). In the case of ketene silyl ketals, however, only a minor amount of arylation occurs. Now the major reaction is the incorporation of the arenediazonium unit so that the corresponding hydrazones are produced (idem, ibid., 289).

OMe

PhN2BF4

Ph ~-~~OSiMe3

-----~pyridine

OMe

OMe

Ph , , ~ O Ph

+

Ph . , ~ O NNHPh

2% 83% Arenediazonium tetrafluoroborates in the presence of a palladium(0) catalyst also arylate alkenes terminated by a trimethylsilyl group. Mixed products result, some of which retain the silyl group while in others it is lost (K.Kikukawa et al., J. Organomet. Chem., 1984, 270, 277). ArN2BF4 SiMe 3

Pd(0)

..--

Ar ~

SiMe3

+

+

SiMe 3

Ar

Ar = Ph, 4-MeC6H4, 4-BrC6H4, 4-I-C6H4, 4-1C6H4. K.Kikukawa et al. (ibid., p.283) have also shown that arenediazonium tetrafluoroborates when treated with palladium(0) catalysts and triethylsilane (or polymethylhydrosiloxane), under an atmosphere of carbon monoxide, afford the corresponding araldehydes. Similarly, benzenediazonium chloride in aqueous acetonitrile containing Pd(0), generated in situ, phenylates prop-2-enol giving a mixture of 2-phenylpropanal and 0~-methylphenylacetaldehyde (K.Kikukawa et al., Tetrahedron, 1981, 37, 31). Arylation of alkenes may also be initiated in the presence of Ti(III) salts. Thus arenediazonium tetrafluoroborates react with alkenes (RCH=CHR, R = CO2H, CO2Me, CONH 2, CN) to give styrenes [Ar(R)C=CHR]

241 (A.Citterio, A.Cominelli and F.Bonavoglia, Synthesis, 1986, 308). However, arenediazonium salts when reacted with 4-methyl-3-penten-2-one give N-phenyldiazenyl derivatives (1). Reductive arylation, the expected reaction, is not observed (A.Citterio et al., Tetrahedron Letters, 1980, 21, 2909).

o

I"

Ph

(i) Arenediazonium chlorides, can be used for chloroarylation. For example, 2,3-dichloro-l,3-butadiene on treatment with benzenediazonium chloride gives 1-phenyl-2,3,4-trichlorobut-2-ene (A.V.Babakhanyan, S.V.Toganyan and V.O.Babayan, Arm. Khim., Zh., 1979, 32, 232; B.B.Grishchuk and N.I.Ganushchak, Izo. Vyssh. Uchebu. Zaved. Khim. Tekhrol., 1980, 23, 1210). In another illustration 4,4'-bis(diazonium)biphenyl dichloride (2) has been shown to arylate 2-vinylpyridine in the presence of copper(I) chloride. The solvent is a 1"1 mixture of water and acetone and the product is 4,4'-bis[2-chloro-2-(pyrid-2-yl)eth-l-yl]biphenyl (3). This compound can be dehydrochlorinated with potassium hydroxide in ethanol to yield 4,4'-bis[2-(pyrid-2-yl)ethen-l-yl]biphenyl (4). (N.I.Ganushchak, I.Yu.Prokopishin and A.I.Zyubrik, Ukr. Khim. Zh., 1980, 46, 81).

CIN2-XX-N2CI

PyCH(CI)CH2-XX-CH2CH(CI)Py

(2)

(3)

PyCH=CH-XX-CH=CHPy (4)

xxHowever, benzenediazonium chloride in the presence of copper(I)

242 chloride phenylates 4,4'-bis(2-cyanoethen-l-yl)biphenyl (5) to afford 4,4'-bis[(2-cyano-2-phenyl)eth-l-yl]biphenyl (6). The product on treatment with sodium hydroxide eliminates hydrogen cyanide to give 4,4'-bis(2-phenethen-l-yl)biphenyl (7) (N.I.Ganushchak et al., ibid., 1981, 47, 887).

NCCH=CH~

CH=CHCN (5)

NC(Ph)CHCH2~

CH2CH(Ph)CN

(6)

PhCH=CH~

CH=CHPh (7)

In more work of this kind it has been demonstrated that arenediazonium tetrafluoroborates react with methyl acrylates and the salts of N,N-diethyldithiocarbamic acid to give arylated derivatives (8), plus minor amounts of arylalkenes (9), and dithiocarbamates (10) (N.I.Grishuck et al., Zh. Obsch. Khim., 1990, 60, 432).

CO2Me R

+

ArN2BF4 Ar CO2Me M- S2CNEt2 '-~ R~X~S2CNEt2 Hflacetone pv

(8) o~,p,p-Trifluorostyrene undergoes arylation and coupling when it is reacted with arenediazonium salts and potassium thiocyanate in acetone solution at ca -30 ~ (E.E.Bilaya et al., Zhur. Obsch. Khim., 1986, 56, 1916).

243 CO2Me +

Ar

~

R

+

(9)

Ar - S2CNEt 2 (10)

(M+= NH 4, Na. or K) F

Ar

Arenediazonium tetrafluoroborates (ArN2BF4; Ar = Ph, 4-MeC6H 4, or 2,4-Me2C6H 3) react with sodium carboxylates (RCO2Na; R = Et, Me2CH, or Ph) and acetonitrile, or benzonitrile, to give the appropriate N-acylanilides (RCON(Ar)COMe or RCON(Ar)COPh respectively) (K.Kikukawa et al., Bull. Chem. Soc., Japan, 1982, 55, 3671). Palladium(II) acetate catalysed cross-coupling using tetramethylstannane as a source of methyl 'radicals' can be employed to convert arenediazonium tetrafluoroborates into the corresponding methylated arenes (N.A.Baumagin et al., Izv. Akad. Nauk. SSSR., Ser. Khim., 1990, 2665). 2,3-Dihydrobenzofurans are formed from 2-(O-allyl)benzenediazonium tetrafluoroborates by the action of copper(H) halides (chloride, or bromide) in dimethylsulphoxide. It is likely that aryl radicals are involved in these reactions and that a radical chain mechanism operates. Presumably there is sufficient copper(I) ion available to initiate the reaction which requires an interaction between the arenediazonium salt and copper(I) ion to generate a aryldiazene radical and copper(II) ion. Loss of nitrogen then affords an aryl radical which cyclises to form a dihydrobenzofuran radical. In turn this species reacts with copper(II) bromide producing the dihydrobenzofuran and copper(l) ion, thereby extending the chain reaction. Only the product from an 5-exo trig. cyclisation is observed (G.F.Meijs and A.L.Beckwith, J. Amer. Chem. Soc., 1986, 106, 5890).

244

N2BF4

Cu 2+

DMSO R (R = H or Me)

ArN2 ~ + Cu 2+

ArN 2+ + Cu + ArN2 ~ Ar ~ R~ +

CuBr 2

~ t ~

Ar ~ + N 2 ,._'.-

------I~

R 9 RBr + Cu + + Br-

Ar = 2-O-allylphenyl; R = 2,3-dihydrobenzofuran-3-yl

The above mechanism is a familiar one, similar to that suggested for the Sandmeyer and related reactions, and in similar work ferrocene, or a mixture of ferrocene and ferrocenium ion, instead of copper salts, can be used to generate the presumed aryl radicals (A.L.Beckwith, R.A.Jackson and R.W.Longmore, Austral. J. Chem., 1992, 45, 857). 2,5-Bis(2,3,3-trimethylbut-2-yl)benzenediazonium hydrogensulphate, prepared by diazotization of 2,5-bis(2,3,3-trimethylbut-2-yl)aniline (11) with sodium nitrite/sulphuric acid, on thermolysis gives 2,5-bis(2,3,3-trimethylbut-2-yl)phenol (12), together with 1,1,2,2-tetramethyl-5-(2,3,3-trimethylbut-2-yl)indane (13). The latter product probably arises through a cyclodeamination reaction involving the participation of an arene radical (S.Rein and P.Martinson, Acta Chem. Scand., Ser. B, 1979, B33, 773). (b) Replacement of the diazo unit by other functions Examples of this type of reaction are, of course, observed in the previous section, but here the emphasis is upon the replacement of the diazo unit by various atoms and simple functional groups. Such reactions can often be facilitated by the use of phase-transfer catalysts and this topic has been reviewed (G.W.Gokel et al., lsr. J. Chem., 1985, 26, 270).

245

C(Me)2C(Me)3

C(Me)2C(Me)3 OH

NH 2

C(Me)2C(Me)3 (11)

C(Me)2C(Me)3

C(Me)2C(Me)3

(12)

(13)

Arenes Arenediazonium tetrafluoroborates bearing electron withdrawing groups are protodediazoniated when reacted with formamide and triethylamine. The mechanism of the reaction is assumed to involve the transfer of a hydrogen atom of the formamide to the substrate to form an intermediate 1-aryl-3-formyltriazene (M.D.Treadgill and A.P.Gledhill, J. Chem. Soc., Perkin Trans. 1, 1986, 873). HCONH 2 ArN2BF4 ~ ArN=NNHCHO

--9 ArH

Et3N In similar procedures arenediazonium fluoroborates are easily reduced to the corresponding arenes by warming them in N,N-dimethylformamide. When the diazonium salt has an electron withdrawing substituent in the aryl ring the reaction proceeds at 25-45 ~ but if an electron donating group is present then the reaction requires a temperature of 65 ~ (R.J.Lahoti et al., Indian J. Chem., Sect. B, 1981, 20B, 767). Triphenylphosphine is another reductant for this type of reaction and 4-nitro-, 4-methyl- and 4-methoxy-benzenediazonium fluoroborates are readily converted into the corresponding arenes by treatment with this reagent in an alcoholic solvent and in the dark. Small amounts of biaryls are formed as by-products (S.Yashui et al., J. Chem. Soc., Perkin Trans. 2, 1994, 177). Halogeno compounds Methods for the preparation of fluorobenzenes from arenediazonium salts have been surveyed (N.Yoneda and T.Furuhara, Yuki, Gosei Kagaku,

246

Kyokaishi, 1989, 47, 619). Aryl fluorides are readily formed from arenediazonium hexafluorophosphates by treating them with boron trifluoride diethyl etherate (K.Shinhama et al., Syn. Commun., 1993, 23, 1577). 4-Fluorophenols are conveniently synthesised by the diazotisation of 4-aminophenols, and fluorodediazoniation is then achieved by heating the salts with hydrogen fluoride in pyridine solution (T.Fukuhara et al., J. Fluorine Chem., 1991, 51, 299). Sandmeyer reactions, particularly iodination, iodothallation, and other applications covering the literature from 1965 to 1985, are summarised by E.B.Merkushev (Synthesis, 1988, 923). In addition, the mechanisms of the Sandmeyer and other related reactions are reviewed by C.Galli (Chem. Reviews, 1987, 1755). As suspected previously a radical chain mechanism seems most probable (see section ii a) and in line with this there is evidence that in the Sandmeyer chlorodediazoniation process the yield of chlorobenzene is not changed by variations in the amount of the copper(I) chloride present in the reaction mixture (W.Dai, Huaxue Tongbao, 1989, 43, 56; CA., 1990, 112, 35339a). Promotion of the reaction by copper(l) ion is not mandatory and, for example, aryl chlorides can be generated from arenediazonium tetrafluoroborates by treating them with iron(II) and iron(Ill) chlorides in carbon tetracloride/acetonitrile (K.Daasbjerg and H.Lund, Acta Chem. Scand., 1992, 46, 157). Aniline can be diazotised when polyethylene glycol is the solvent. Solutions of the benzenediazonium halides so formed can then be utilised in Sandmeyer type reactions leading, for example, to improved yields of chlorobenzene, bromobenzene, and benzonitrile compared to those of conventional procedures (N.Suzuki et al., J. Chem. Soc., Chem. Commun., 1984, 1523). Benzenediazonium chlorides react with peracids in 50% aqueous acetic acid solution to give 2-chlorophenols. It is argued that these reactions involve aryloxychlorides as intermediates. When the concentration of peroxide, with respect to the diazonium salt, exceeds 1:2 both di- and tri-chlorophenols may form (Y.Furuya et al., Yukagaku, 1984, 33, 86; C.A., 1985, 102, 112958z). Aryltriflates Aryluiflates are available from arenediazonium tetrafluoroborates by thermal, or photochemical, induced decompositions in the presence of either trifluoromethanesulphonic acid, or trifluoromethanesulphonic anhydride (N.Yoneda et al., Chem. Letters, 1991, 459).

247 Nitroarenes 4-Nitrobenzenediazonium tetrafluoroborate reacts with sodium 4-nitrobenzenediazotate in acetonitrile solution to give 4-nitrophenol and nitrobenzene. In dimethylsulphoxide solution nucleophilic substitution of the nitro group by the diazotate ion occurs giving the zwitterion, 4-diazophenol (-O-C6H4N2+-4) (N.B.Kupletskaya et al., Zhur. Org. Khim., 1986, 22, 542; N.B.Kupletskaya and L.A.Kazitsyna, ibid., 1237). Arylazo exchange is noted in the reactions of 4-substituted arylazophenols with 4-nitrobenzenediazonium tetrafluoroborates in pyridine solution (K.Imafuku, J. Chem. Res., Synop., 1984, 342). Alcohols and phenols Dediazoniation of 2-(2-ethylphenyl)benzenediazonium chloride in a warm aqueous medium gives 2-ethyl-2'-hydroxybiphenyl (1), 9-methylfluorene (2), and 2-(1-hydroxyeth-2-yl)biphenyl (3) (W.R.Stumpe, Tetrahedron Letters, 1980, 21, 4891).

~

H20 -

N2

-HCI

(2)

(I)

(3)

Thiols and related compounds Diazonium groups can be replaced by hydrogen, or deuterium using thiophenol, or its deuterated analogue (PhSD) respectively, as reductants. Quantitative isotopic purity is observed in these reactions, which may involve free radical mechanisms (T.Sono, Y.Matsumura and K.Tsubata,

248 Chem. Letters, 1979, 1051. Arenediazonium tetrafluoroborates when reacted with alkali metal thiocarboxlates (RCOSK, or RCOSNa; R = Me,. or Ph), in dimethylsulphoxide afford arylthioesters (ArSCOR). The reactions proceed through the initial formation of 1-aryldiazen-2-yl thioesters (ArN=NSCOR) which fragment to give aryl radicals. These recombine with either thiocarboxylate anions (RCOS-), or the equivalent radicals in a solvent cage, to give the final products (G.Petrillo et al., Tetrahedron, 1989, 45,

711).

Reactions of 1,4-bis(diazonium)benzene di(tetrafluoroborate) with disulphides (R2S2; R = Ph, Bn etc.) in the presence of copper(II) chloride lead to the formation of 4-chlorophenylthiobenzene (4) and/or 1,2-bis(phenylthio)benzene (5). The result obtained depends upon the solvent used (L.V.Yashkina, B.V.Kopylova and R.Kh.Friedlina, lzv. Akad. Nauk. SSSR., Ser. Khim., 1980, 212).

F4BN2~

N2BF4 (4)

SLVS (5) Ketones Benzenediazonium tetrafluoroborates are converted into diaryl ketones by the action of stannanes and carbon monoxide in contact with palladium(II) acetate as catalyst. An alkyl group of the stannane becomes incorporated into the aroyl unit (K.Kikukawa et al., J. Chem. Soc., Perkin Trans. 1, 1987, 1511).

249

R4Sn/CO .=9

ArN2+BF6 -

ArCOR

Pd(OAc) 2

Carboxylic acids Palladium catalysed carbonylations are also used in the synthesis of carboxylic acids. Thus arylamines can be converted into arene carboxylic acids, via their arenediazonium tetrafluoroborates, by reactions with carbon monoxide under high pressure in the presence of a palladium catalyst and sodium acetate (N.T.Nagira et al., J. Org. Chem., 1980, 45, 2365). Other catalysis are similarly effective and arene carboxylic acids are conveniently synthesised from arenediazonium tetrafluoroborates by reacting them with carbon monoxide in aqueous dioxane in the presence of cupric chloride (G.A.Olah et al., Syn. Letters, 1990, 596). (c) Azo coupling A selection of representative coupling reactions are recorded here, other examples will be found in other sections throughout this chapter. The sigma complex formed during the coupling of 4-nitrobenzenediazonium chloride and N,N-dimethylaniline can be observed as an inclusion compound trapped within the cavity of cyclodextrin (H.Ye, W.Tong and T.D'Souza, Tetrahedron Letters, 1992, 33, 6271). Phenacylthiocyanates couple with arenediazonium chlorides to form hydrazones, not thiadiazol-2-imines as previously thought (M.H.Elnagdi et al., Spectrochim. Acta, 1990, 46A, 51). Diazo coupling between hydroxycalix[4]arenes and 4-nitrodiazonium salts is a selective process affording tetrasubstituted calix[4]arenes. No mono-, di-, or tri-substituted products are observed, even when excess of the hydrocalix[4]arenes are present. This 'all-or-nothing' substitution is considered to be the result of specific hydrogen bonding with the hydroxyl groups of the substrate (S.Shinkai et al., J. Chem. Soc., Perkin Trans. 1, 1989, 195); (for other studies in this area also see M.-1.Yeh et al., J. Org. Chem., 1994, 59, 754). Interestingly, resorcinol based tetrameric cyclophanes couple with the 4-sulphonatobenzenediazonium zwitterion at the para positions to give water soluble host molecules (K.Asakura et al., Chem. Letters, 1990, 1219).

250

/

I

a

R

w

N,,-N

so; The diazotisation of various [2.2]metacyclophanes has been used to show that the electronic effects of substituent groups in the metacyclophanes are transmittable between the two aryl tings by through-space interactions, propably through the agency of charge-transfer complexes. Thus the reactivity of one ring is enhanced and the other reduced towards coupling with diazonium salts (A.Tsuge et al., J. Chem. Soc., Perkin 2, 1993, 2211). (d) Applications to the synthesis of nitrogen containing heterocycles Indoles 2-Acetylindoles (2; R = H, Me, OMe, C1; R 1 = Me, or Ph) are conveniently synthesised by reacting 4-substituted benzenediazonium chlorides with substituted ethyl acetoacetates, and heating the product hydrazones (1) in boiling hydrochloric acid (S.B.Rajur, A.Y.Merwade and L.D.Basanagoudar, Syn. Commun., 1992, 22, 421).

R'Ct.o R1

MeCOCH(CH2R)CO2Et

Me

N2CI I

H

(I)

251 R1

HCI O

(2)

H

Pyrazoles, pyrazolines, and pyrazolidines Chloroacetoacetanilides (At = C6H4R-4; R = Me, or MeO) on coupling with benzenediazonium chloride give hydrazones (1) which cyclise in hot ethanol containing sodium acetate to give pyrazolinones (2) (I.A.Mohamed et al., Egypt. J. Chem., 1976, 195).

O Ci,v ~

PhN2Ci CI~.~N"~ON//L EtOH/NaOAc/ ~ O H ~ p,./Iq,../~ CONHPh CONHAr Ph" -" CONHArA " N (1)

(2)

Pentane-2,4-dione and arenediazonium chlorides afford the corresponding 3-(aryldiazenyl)pentane-2,4-diones (3). These products react with acylhydrazines to yield the pyrazoles (4) (V.S.Jolly, G.D.Arora and P.Talwar, Indian J. Chem., 1990, 67, 1001).

N=NAr @ O

NH2NHCOCHsCONHAr~ O

(3)

N=NAr e

COCH2CONHAr (4)

Indazoles Diazotisation of 2-aminoaryl chloroalkyl ketones, followed by reduction

252 of the diazonium salts through the addition of stannous chloride to the reaction mixtures, leads to 3-(2-chloroethyl)indazoles (K.Sasukura, A.Kawasaki and T.Sugasawa, Syn. Commun., 1988, 18, 259).

(~CH2) NN t 2CI

R~NHO(cH2)2cl 2

R

"H

A simple route to indazoles requires the reaction of arenediazonium tetrafluoroborates with potassium acetate in the presence of a crown ether (R.A.Bartsch and I.W.Yang, J. Het. Chem., 1984, 21, 1063).

R~~~L~ KOAc/18-crown-6~,R~~~N~ ._ N N2BF4 H

Pyrazines Ethyl 4,4-dicyano-3-methylbut-3-enoate reacts with arenediazonium chlorides to form 6-amino- 1-aryl-5-cyano-3-ethoxycarbonyl- 1,4-dihydro -4-methylpyrazines, which exist preferentially as the imino tautomers (G.H.Elgemeie et al., Arch. Pharm., 1989, 322, 539).

Me

I.Me ArN2CI EtO2C ~CN EtO2C~ CN ~__ NH CN Ar

253 Benzotriazines Benzenediazonium salts couple with 1,3-diaminobenzene to give 2,4-diaminoazobenzene (1, R=H), which on treatment with ethyl chloroformate in pyridine affords the dicarbamate (1, R=CO2Et). This in turn cyclises and hydrolyses in the presence of hydrochloric acid to give 6-amino-2,3-dihydro-2-phenyl-l,2,4-benzotriazin-3-one (2) (J.Sluaka and B.Vojtech, Collect. Czech. Chem. Commun., 1980, 45, 1379).

N=NPh

N.N.,

RHN,~NHR (1)

H2N

(2)

Pyrido[1,2-c]benzo-v-triazinium tetrafluoroborates can be synthesised by generating diazonium tetrafluoroborates from 2-(pyrid-2-yl)anilines. Thus the diazonium salts can be regarded as acyclic valence tautomers of the triazinium species (A.Messemer, J. Het. Chem., 1987, 24, 1133).

v

R

!

R BF4-

Tetrazoles Tetrazolium salts (2) are prepared by the reaction of diazonium salts (ArN2X; X = Br, or I) with phenylhydrazones, followed by oxidation of the products (1) with hydrogen peroxide in the presence of ferrous ion and ion exchange (D.D.Mukerjee et al., Acta Pharm., Jugosl., 1981, 31, 151).

254

N

CH=NNHPh

J

NHPh

ArN2 x , N=NAr

(1) Ph I

N SN N +- Ar

H202/Fe 2+ v

X(2)

Tetrazole macrocycles (6) have been synthesised by reacting arenediazonium chlorides with malonodinitrile and treating the product hydrazones (3) with sodium azide, ammonium chloride, and lithium chloride in dimethylformamide. This affords the corresponding tetrazoles. Two equivalents of the tetrazoles react with et,~dibromoalkanes in the presence of base to yield the corresponding a,~di(tetrazolyl)alkanes (4). Further treatment with sodium azide and then reaction of the products (5) with more a,~dibromoalkane and base produces the macrocycles (R.N.Butler, K.F.Quinn and B.Welke, J. Chem. Soc., Chem. Commun., 1992, 1492).

ArN2CI

CH2(CN)2 ~

/ CN ~ CN ArNH - N

(3)

NaN 3 / NH4CI/LiCl "= .v

255

ArN2CI

/ CN ~

CH2(CN)2 ~

NaN 3 / NH4CI/LiCI "= CN

ArNH - N

(3) CN ArNH - N

N,.

Br(CH2)nBr

CN

CN

/'~"~/N"N~N" N ~ ~ \

xN __.N

K2CO3 ArNH - N

N= N

N= N

NHAr

N-

(4) H

H

/ NaN 3/NH4CI/LiCI

t

N

I~ N"N'/,N

N~ "N I~i'

"f~N" ArNH ~

N-.N

K2CO3

N=N /

(5) N~.N,N ~

~r.."

N

.

N.'N,'N

,,,,~

N<'N - N,~nN..N ~N

(6)

Br(CH2)nBr

N/

"N -NHAr

256 9. Arylhydrazines and arylhydrazones The chemistry of the arylhydrazines and that of the arylhydrazones are intimately related and it is difficult to treat them as individual topics. Indeed, arylhydrazines are most commonly employed to generate arylhydrazones, although the latter may be reacted further without isolation. A typical example is in the Fischer indole synthesis (see below), here a carbonyl compound is reacted with an arylhydrazine to afford an indole. An arylhydrazone is formed initially, but it is often convenient to treat this directly with acid whereupon rearrangement and cyclisation occur 'in the same pot' to form the corresponding indole. In the following sections it will be noted that, although an attempt has been made to separate synthetic methods and some of the chemical reactions of the two groups of compounds, there is considerable overlap particularly in the application of these compounds to the synthesis of heterocycles.

(i) Synthesis (arylhydrazines) Arylhydrazines (ArNHNH2) are synthesised by reacting either aryllithiums or arylmagnesium bromides with di(tbutyl)azo dicarboxylate, followed by hydrolysis and decarboxylation of the initially formed adducts (J.P.Delmers and D.H.Klaubert, Tetrahedron Letters, 1987, 28, 4933). Arylhydrazines (ArNHN(R')R can be obtained from N-(diphenylphosphonoyl)arylamines [ArNHOP(O)Ph 2, Ar = C6H5, 4-C1C6H4, ,3-NCC6H4, 4-MeC6H4] by amination with secondary alkylamines (RNHR) (G.Boche and R.H.Sommerlade and F.Bosold, Angew. Chem., 1986, 98, 563). Formaldehyde, or hydrazine, are recommended reagents for the reduction of hydrazones to hydrazines (M.R.Islam et al., Bangladesh. Chem. Soc., 1990, 3, 141; CA., 1991, 114, 184888x). 1,1-Bis(2-methoxyphenyl)hydrazine [(2-MeOC6H4)2NNH2] is prepared in 50-80% yield by the Hofmann amide degradation of N,N-bis(2-methoxyphenyl)urea itself made by treating N,N-bis(2-methoxyphenyl)amine with either sodium isocyanate, or chlorosulphonyl isocyanate (Y.Murakami and Y.Yokoyama, Heterocycles, 1979, 12, 1571).

257

(ii) Reactions (arylhydrazines) a. Action as reductants Phenylhydrazine acts as a reductant for tetrakis(phenylimino)cyclobutane) giving 1,2-bi s (phenylamino)- 3,4- bi s(phenylimino)cyc lobutene ( 1) (J.B.Hans, G.Schmid and E.Wilhelm, Angew. Chem., 1980, 92, 134).

pPhhN~N N- NpPhh

PNHNH 2

pPh hNN~[~NH NHpPh h (1)

b. Alkylation and acylation It is possible to N-arylate 2-aroyl-l-(4-nitrophenyl)hydrazines (ArCONHNHC6Hn-4-NO2) by reacting them with aryl iodides in ethanol containing sodium ethoxide and cuprous iodide (V.P.Zhestkov, V.G.Voronin and Yu N.Portnov, Zh. Org. Khim., 1986, 22, 1560). Arylhydrazines are N-acylated by reaction with acid anhydrides first at the primary amino group and then at the secondary amino site (M.J.Hearn et al., J. Chem. Eng. Data., 1985, 30, 129; M.J.Hearn and J.E.Grimwade, Org. Prep. Proced. Int., 1980, 12, 249). However, when phenylhydrazine is reacted with excess acetic anhydride in the presence of 4-(dimethylamino)pyridine 1,1-diacetyl-2-phenylhydrazine is formed (H.Egg et al., Syn. Commun., 1992, 22, 1199). Other acylating agents also react at the primary amino group. Succinic anhydride, for example, forms the corresponding imide. This product is sufficiently stable to allow further reactions with more vigorous electrophiles which may attack the aromatic nucleus. Thus a reaction with sulphuryl chloride gives 2,4,6-trichlorophenylhydrazine, after removal of the N-acyl group by hydrolysis with concentrated hydrochloric acid in methanol [M.Fujiwara and T.Komjima, Eur. Pat. Appl. E.P. 208477 (1987); C.A., 1987 106 10186t]. N-Acylation at the secondary amino position is claimed to occur when arylhydrazinium chlorides are reacted with aroyl chlorides in dichloromethane solution [Spain P.E.S. 542369 (1985); C.A., 1987, 106, 18136r1.

258 c. Use as arylating agents Arylhydrazines react with dialkoxy disulphides in benzene at reflux to give biaryls, diaryl sulphides, and arylalkoxy tetrasulphides. Thus 4-nitrophenylhydrazine combines with diethoxy disulphide to give 4-nitrobiphenyl, ethoxy 4-nitrophenyl tetrasulphide and di(4-nitrophenyl) disulphide (H.Kagami and S.M.Ki, Bull. Chem. Soc., Jpn., 1979, 52, 3463). A plausible mechanism requires initial formation of a diazo disulphide (1) which reacts with more of the starting material to yield an unstable diazo tetrasulphide (2). This fragments, with loss of nitrogen, to afford an aryl radical, plus the ethoxy tetrasulphide radical (3). The radicals can couple with each other to produce an arylethoxy tetrasulphide, or with the solvent benzene to give a diaryl. Aryl ethoxy tetrasulphides are also unstable under the reaction conditions and decompose to diaryl tetrasulphides and diethoxy tetrasulphide: -EtOH ArNHNH 2 +EtOSSOEt ~ ArNHN---S=S ~ EtOSSOEt -EtOH Ar'+

ArN=NS4OEt ~ (2)

Ar" +

ArN=NSSH

EtOS4" + N2

(1)

Ar-C6H5 + H"

C6H6 ~

Ar ~ + EtOS4"---i~

ArS4OEt

(3) 2 ArS4OEt..--I~

ArS4Ar + EtOS4OEt (4)

(5)

The photolysis of 1-phenyl-2-sulphinylhydrazine (6) in aromatic solvents (C6H5-C1, -Br, or -OMe) gives the appropriate o-, m-, or p- substituted biphenyls (7).

259

C,H,X NHN:SO

.~ hv

X

(6)

(7)

Presumably the phenyl radical is generated first, and this then couples with the solvent. However, if nitrobenzene or pyridine are used as solvents phenylation is inhibited [G.DeLuca, G.Renzi and A.Pizzabiocca, Chem. Ind. (London), 1979, 899; J. Chem. Soc., Perkin Trans. 1, 1980, 1901]. 4-Nitroarylhydrazines generate the corresponding 4-nitroaryl radicals in the presence of copper(II) sulphate. These radicals may be trapped by methyl acrylate to yield 1:1 adducts (4-NO2ArCH2CH2CO2Me), together with smaller amounts of 1:2 addition compounds (4-NO2ArCH2CH(CO2Me)CH2CH2CO2Me) (T.Varea et al., Tetrahedron Letters, 1989, 30, 4709). 1,2-Dimethyl-l-phenylhydrazine undergoes oxidative coupling when reacted with tungsten oxytetrafluoride giving the dehydrodimer (8) and the complex dianion (9) (S.G.Sakharov, Yu.V.Kokunov and Yu.A.Buslaev, Dolk. Akad. Nauk., SSSR., 1985, 283, 163). .

/

Me

N-N Ph

Me

Ph

I

N-N

N-W

F4 ~ N - Me I Ph

(8)

,o

-

o "W-

Me

F4

(9)

Phenylhydrazine gives benzene, azidobenzene, aniline, biphenyl, azobenzene, and a trace of diphenylamine when it is oxidised at 20-25 ~ with aqueous sodium periodate in contact with an aliphatic ether as co-solvent. Phenylhydrazones and phenylazo alkyl ethers are also formed, and when aryl ethers are used phenylated-aryl ethers are detected (M.Tsuboi, Nippon Kagaku Kaishi, 1986, 1102; 1990, 179).

260 Arylamines, or arylhydrazines, can be used as arylating agents for alkenes in the presence of palladium(H) salts in acetic acid. For example, aniline, phenylhydrazine, or hydrazobenzene phenylate styrene and yield (E)-stilbene (Y.Fujiwara, M.Abe and H.Taniguchi, J. Org. Chem., 1980, 45, 2359). d. Use in the synthesis of diazenes etc. S-Methyl-N-nitrothiourea [MeSC(=NNO2)NH 2] and phenylhydrazine combine together to form the phenylhydrazinylnitrourea [PhNHNHC(=NNO2)NH2], which can be oxidised by bromine to yield the diazene [PhN=NC(=NNO2)NH 2] (O.A.Luk'yanov, T.G.Mel'nikova and Yu.A.Strelenko, Ivz. Akad. Nauk. SSSR. Ser. Khim., 1991, 1115). N-(Arylamino)guanidinium chlorides (ArNHNHC(=NH)NH3 + C1-) are readily prepared from the corresponding arylhydrazinium chlorides and N,N-dimethylaminonitrile [I.Erczi et al. Ger. Often., D.E. 3,445,339 (1985); C.A., 1986, 104, 109273h].

(iii) Physical properties (arylhydrazones) The crystal structure of (E)-benzaldehyde phenylhydrazone shows it to exist as a monoclinic, ordered molecule (space group P21/c), in which the angle between the benzene tings is 8.1(1) ~ (B.Vickery et al., Acta Cryst. Sect. C, Cryst. Struct. Commun., 1985, C41, 1072; also see M.G.B.Drew and G.R.Willey (Educ. Chem., 1985, 22, 106). Benzil monophenylhydrazone exhibits photochromic and thermochromic properties. In its lowest energy form the molecule has the trans-E conformation (1), but on irradiation this changes to give the cis-Z-isomer (2) (U.Miiller, H.J.Timpe and K.Gustav, J. Prakt. Chem., 1984, 326, 876).

Ph

0

PhNH- N

Ph

Ph

Ph NHPh (1)

(2)

261 (iv) Synthesis (arylhydrazones) Conventionally prepared 2,4-dinitrophenylhydrazones typically contain traces of acids, this has the effect of depressing their melting points. To avoid this problem such products should always be washed with sodium bicarbonate solution (M.Behforouz, J.L.Bolan and M.S.Flint, J. Org. Chem., 1985, 50, 1186). 2-(Arylhydrazono)cyclohexanones are synthesised by reacting arenediazonium salts with 1-trimethylsilyloxycyclohexene in acetonitrile as solvent [R.Sell, K.Kuehlmann and R.Czerwonka, D.D., 240 007 (1986); CA., 1987, 107, 6931d].

[~

OSi(Me)a

~

ArN2X/CH3CN

Ar ~N

~ I

H

Ambazone (1) is reduced by ascorbic acid to its aromatic dihydro derivative (2) which shows bacteriostatic and antineoplastic activity [H.Schulze et al., D.D., 267 252 (1989); C.A., 1989, 111, 21246u)] C(NH2)2

C(NH2)2

II

N" I

N

"N I

II

H

NH2

"N"

N

H"N~N

NH2

I

H

H

(1)

(2)

Three compounds are formed when squaric acid is reacted with phenylhydrazine: cyclobutanetetraone tetrakis(phenylhydrazone) (3), and the products (4) and (5) which contain two and three phenylhydrazine residues in various states of oxidation, respectively. The last compound (5) is in equilibrium with the tautomer (6) (H.S.E1Khadem et al., J. Chem.

262 Soc., Perkin Trans. 1, 1992, 1511). Ph "N.. N

Ph N..N/ // "H

Ph"N .. N/J

I~N..N -H

H"

\\

/

H

Ph H

Ph

"Ph (4)

(3)

Ph

H I

Ph "N.. N

N=Nt

H

H

H i Ph N..Nt

Ph "N.- N

H

h

N"N I Ph

Nr N

Ph

H (5)

(6)

(v) Chemical reactions (arylhydrazones) a. Hydrolysis Baker's yeast is recommended for the release of aldehydes and ketones from their hydrazones (A.Kamel, M.V.Rao and H.M.Meshram, Tetrahedron Letters, 1991, 32, 2657). Oxidative methods using dimethyldioxirine are also used when the presence of acid may cause the product carbonyl compounds to undergo condensation reactions (A.Altamura, R.Curci and J.O.Edwards, J. Org. Chem., 1993, 58, 7289). b. Oxidation Five coordinate Co(II)- Schiff base complexes mediate the oxygenation of 4-nitrophenylhydrazones (1) to give 1-(4-nitrophenylazo)-l-peroxycobalt(III)ethylbenzene complexes of the type (2), which with silica gel shed the metal and give 1-(4-nitrophenylazo)-l-hydroperoxyethylbenzenes (3). (A.Nishinaga et al., Tetrahedron Letters, 1982, 23, 339).

263 R

O2/C~ c:= NNHAr

R OOCo(lll) Me

R

H+

N=NAr

M~N=NAr

Me

(1)

OOH

(3)

(2)

(Ar = 4-NO2C6H4; R = 4-MeOC6H4)

Related reactions occur when 4-nitrophenylhydrazones of ketones (R2C=NNHC6Hn-4-NO2) are oxidised by tbutylperoxy(N,N'-disalicylidenediaminato)cobalt to give the corresponding 1-tbutyldioxy-l-(4-nitro phenylazo) compounds [R2C(OOtBu)N=NC6H4-4-NO2] (A.Nishinaga et al., Nippon Kagaku Kaishi, 1985, 378). Oxygenation of the arylhydrazones of benzaldehyde, or those of acetophenone [PhC(R)=NNHAr; R = H, or Me; Ar = Ph, or 4-MeC6H4], similarly affords the corresponding azoperoxides [Ph(R)C(OOH)N=NAr]. However, these products are only stable as solvates of petroleum ether, benzene, or ~propanol etc. Removal of the solvent causes decomposition, probably through the agency of the appropriate arenediazonium ions (T.Tezuka and S.Ando, Chem. Letters, 1985, 1621). c. Oxidative coupling When benzyl ketone 4-nitrophenylhydrazones (Ar = C6H4NO2-4) (1) are treated with mercury(II) acetate in acetic acid hydrazino transfer occurs to form substituted phenylglyoxal bis(N-4-nitrophenylhydrazones) (2). In addition, some C-acetoxylation occurs at the a-carbon atom of the benzyl group giving 3-acetoxy-l,2-bis(N-arylhydrazono)propanes (3) and (4) (R.N.Butler and G.J.Mori, J. Chem. Soc., Perkin. Trans. 1, 1980, 2218. 2RCH2 -

~ :((1NNHAr

1RCH2

)

Hg(OAc)2

2R

~ HOAc (R1 = R 2 = Ar)

1

R

.. NNHAr NNHAr

(2) Hg(OAc)2 ~ (RI = H" R2 = Ar)

264 2 R

H"

2 R

.. NNHAr

1R

Ac

" NNHAr

(3)

(4)

d. Reduction Selective hydrogenation of the nitro groups of the phenylhydrazones of 4-alkoxy-2-nitrobenzaldehydes is effected under catalytic transfer conditions in the presence of cyclohexene and 10% Pd/C. The corresponding amines are obtained in yields of 80-90% (R.A.Rampulla and R.K.Russell, Synth. Commun., 1986, 16, 1229). Phenylhydrazones of ketones (RR'C=NNHPh) undergo reductive dimerisation with zinc dust in carbon tetrachloride/ethanol to afford 1,2-bis(2-phenylhydrazin-l-yl)ethanes [PhNHNHC(RR')C(RR')NHNHPh] (N.H.Khan et al., Synth. Commun., 1980, 10, 363). Reduction of the 2,4-dinitrophenylhydrazones of aldehydes with Raney nickel in benzene gives good yields of the corresponding 2,4-diaminophenylhydrazines. If the reactions are carried out in the presence of acetic anhydride then the primary amino groups of the products are N-acetylated (M.M.Kidwai and N.H.Khan, Sci. Res. News, 1980, 2, 17). e. Rearrangement reactions Arylhydrazones of benzophenone combine with bromine and pyridine to afford 1-[(arylazo)diphenylmethyl]pyridinium bromides and pyridinium bromide. The former react with methanol acting as a nucleophile to give arylazodiphenylmethyl methyl ethers. Other nucleophiles, including alkoxide ions, acyloxy ions, and amines, can also be used to displace the pyridine unit from the salts (H.Gstach and J.G.Schantl, Syn. Commun., 1986, 16, 741; Monatsh. Chem., 1987, 118, 851).

265

Ph ---~\

,,

Br2

N-N, Ar

\

v"~ py

MeOH

OMe

v

N -

Ph+N--N-Ar, Ph Br N -

Ar

---.--l~ph. I I~' Ph

Ar

Ph

Ph The highly substituted hydrazone (1) rearranges in hot polyphosphoric acid solution to afford the 4'-aminobiphenyl glyoxylate (2) and 2,9-diamino-9-ethoxycarbonyl-6-methoxy-l,3,5,7-tetramethylfluorene (3). It is suggested that the formation of the first product involves a [5,5]-sigmatropic rearrangement, followed by a 1,2-aryl shift (F.Sannicolb, Gazz., 1985, 115, 91). CO2Et

CO2Et

O Me

H2

(2)

(1) EtO2C ,,~

INH2

NH 2

(3) Aryl hydrazones of 4-hydroxyacetophenones and benzophenones when heated with excess polyphosphoric acid at 100 ~ give diaryl ethers and biphenyl derivatives. Thus, the 2,6-dimethylphenylhydrazone (4) of

266

4-hydroxy-3,5-dimethyloxyacetophenone yields 4-acetyl-2,6-dimethylphenyl 4-amino-3,5-dimethylphenyl ether (5), whereas the 2,6-dimethylphenylhydrazone (6) of 4-hydroxyacetophenone gives 4-acetylphenyl 4-amino-3,5-dimethylphenyl ether (7) and 5-acetyl-4'-amino-2-hydroxy-3',5'-dimethylbiphenyl (8) (R.Fusco and F.Sannicolb, J. Org. Chem., 1981, 46, 90). If the hydroxy group is replaced by a thiol substituent then the reaction of the hydrazone gives the corresponding diphenyl sulphide, and when it is replaced by an amino function as in the hydrazone (9) diarylamines (e.g. 10) are produced (F.Sannicolb, Gazz., 1981, 111).

Me

Me

HO M _ . ~ ~ ~ k N

e ~,H

/

-N / ~

Me

z

PPA

AC ' ~ ~

O

"-

Me

Me

Me

Me (4)

(5)

Me

NH2

'e

HX

H t

N- N

Ac Me

X

PPA Me

Me

(6)

(7) Ac

Me

NH2

Me NH2 OH (8)

Me

when X -0

267

_CV< 'e Me

H2N

N-N I

\

Me

H

Me

Me

PPA Y

Me (~-M

Me

NH2

Me

(9)

(10)

f. Reactions as nucleophiles Phenyl hydrazones exhibit three types of reactions with alkenes: nucleophilic attack via carbon, nucleophilic attack via nitrogen, and 1,3-dipolar cycloaddition (through the azomethine imine ylide resonance contributor). The last two effects are well illustrated in the reactions of 2-methyl-l-phenylhydrazines (1) with alkenes such as styrene, methyl acrylate, fumaric acid, or maleic acid (G.LeFevre and J.Hamelin, Tetrahedron, 1980, 36, 887): Me

R---.<\ Phi N-N+.H

Me

R .'-'~\ tPh N-N H

"'...V / Me

R'--~\_ N/Ph N

Me

X, X

R

Ph

R -"
H" '~Ph X

(A)

268

(A) (i) X

x

\

/

..,. R

N"

N

R

~" Me

N~,N'H

" Ph

!

I

H

Ph

Arylhydrazines react with 2,5-bis(arylamino)-3-carboxy-l,4-benzoquinones (2) to give 5-arylamino-2-(arylazo)-l,4-dihydroxybenzenes (3). These reactions may proceed through initial nucleophilic attack of the arylhydrazine at the p-position to the carboxylic acid unit, even though this site is sterically hindered. Decarboxylation then occurs, followed by elimination of one molar equivalent of arylamine. The hydrazones thus formed tautomerise to the aromatic products (3) (W.Schaefer and M.Pardo, Rev. R. Acad. Cienc. Exactas, Fis. Nat. Madrid, 1979, 73, 611).

O ArNH" ~

CO2H

PhNHNH2ArNH

O L,.T/CO2H

-CO 2

, , ~ NHA~-I I N-N/ O H ~Ph

NHAr O (2) O

ArNH

~

I

O--H

O

ArNH

ArNH -ArNH2 NHA~ .~ bN

,-N

O H

"

'Ph

N O

i

N

H ~ \ Ph

O N "H \ Ph (3)

269 Another example of conjugate addition to an enone system is noted in the reactions of phenylhydrazine with 5-alkylfuran-2(5H)-ones. The corresponding 4-(2-phenylhydrazin-l-yl)tetrahydrofuran-2-ones are formed initially, but these react with more phenylhydrazine to yield the corresponding phenylhydrazones (J.Bohrisch et al., Tetrahedron Letters, 1993, 34, 2749). PhNHNH 2 PhNHNH

R

0

R"'

0

PhNHNH PhNHNH 2 NNHPh

g. Uses in heterocyclic synthesis (1) Indoles The Fischer indolisation reactions of arylhydrazones have been reviewed (see N.N.Sovorov, V.N.Shkil'kova and N.Ya. Podhalyuzina, Khim. Gerot. Soedin., 1988, 1443; D.L.Hughes, Org. Prep. Proced. Int., 1993, 25, 607). Evidence has been presented to show that under conditions of high acidity the aromatic ring of the phenylhydrazone may become protonated, as well as the more basic nitrogen atom. When this occurs isomerism of the hydrazone to the corresponding enamine becomes the rate limiting step. Under dilute acid conditions where only N-protonation is observed the rate limiting step is the [3,3] sigmatropic rearrangement which establishes a bond between the aromatic ring and the ~-carbon atom of the enamine (D.L.Hughes and D.Zhao, J. Org. Chem., 1993, 58, 228). The use of microwave radiation to improve the yields in Fischer indolisation reactions is recommended, using 96% formic acid as the reaction medium. This technique i s successful even when the phenylhydrazone contains strongly electron withdrawing groups (R.A.Abramovitch and A.Bulman, Syn. Letters, 1992, 795). Fischer indolisation of the Na-phenyl-2-methoxyphenylhydrazone of ethyl pyruvate in hydrogen chloride and ethanol occurs principally at the unsubstituted phenyl ring to give 2-ethoxycarbonyl-l-(2-methoxyphen-

270 yl)indole (1). The alternative 2-ethoxycarbonyl-7-methoxy-l-phenylindole (2, R = H), plus its 6-chloro derivative (2, R = C1), is also produced, together with the o-, p-, and m-chlorinated diphenylamines (4). It is evident that the methoxyl group assists the fragmentation of the hydrazone to afford the o-iminoquinone cation (3) which traps chloride ion to yield the isomeric diphenylamines (H.Ishii et al., J. Chem. Soc., Perkin Trans.1, 1989, 2407; Chem. Pharm. Bull., 1991, 39, 572).

.eyCOt,.N[••••N

~

r

MeO

Ph

c02Et OMe

(1)

• ~~N)-'-CO2Et Ph

MeO

(2)

MeO+

~?C' MeO

,,H

Ph

(3)

Ph

(4) Similarly, 2,4-dinitroaniline is produced, rather than the corresponding indole, when the 2,4-dinitrophenylhydrazone of cyclohexanone is heated in concentrated sulphuric acid (B.P.Das, M.Y.Jamal, and B.Choudhury, Indian J. Chem., 1990, 67, 72). The formation of arylamines in the attempted Fischer indolisation of arylhydrazones bearing electron donating groups is perhaps a very common event and one which contributes to low yields of indoles. Other reactions which can also reduce the yields include the formation of adducts. For example, in the cyclisation of the phenylhydrazone (5) of

271 2,2,5-trimethylcyclopentanone the amino ketone is formed as a result of hydrolysis of the indolenine (6). In addition, the dimer (7) is produced (J.Y.Laronze et al., Tetrahedron, 1991, 47, 4915). Similarly, when 2-methylindanone is reacted with 4-methylphenylhydrazine and then heated in acetic acid solution cis-4b,5,9b, l O-tetrahydro-8,9b-dimethyl-4b-(4-methylphenylhydrazin-Nb-yl)indeno[1.2-b]indole (8) is formed (D.W.Brown et al., Tetrahedron, 1991, 47, 4383).

H

(6)

(5)

S (7)

A reaction between cyclopropanone and phenylhydrazine in ethanol saturated with dry hydrogen chloride gives 3-(2-chloroethyl)-l-phenylindole in low yield. This product is accompanied by 1,2,3,4-tetrahydroquinazine and 1,2,3,4-tetrahydrocinnoline (B.Robinson and M.J.Shaw, Chem. Ind., 1985, 626).

272

Me

_@,H

4-MeCsH4NHNH2

N

iiv

N

HOAc

AN I

(8)

Me

CH2CH2CI PhNHNH 2 HCI

Ph I

"H N I

H

i H

When 2-(3-oxobutanoyl)-l-methyl-l-phenylhydrazine (9) is reacted with polyphosphoric acid 1,2-dimethyl-8-methylaminonaphtho[3,2,1-c,d]indol-10-one (12) is produced. This involves a complex series of reactions, which possibly requires the formation of the indole (10) as an intermediate. From this compound both arylation and N-N bond cleavage steps occur to give the final product, perhaps via a second intermediate (11) (M.J.Kornet, A.P.Thio and L.M.Tolbert, J. Org. Chem., 1980, 45, 30).

273

0

...Me

0

O

[~ N . . N . H

Me',N, ~ ~

PPA ~

Me ~Me

~e

(10) NHMe

(9)

NHMe I

~-- ~.,L

?ONH2

.-~-DP-

I [ ~ . ~ N,/~_Me

Me

(11) Me

(12) Me

More predictably Fischer indolisation of 3-(4-methoxyphenY~.hyd"_7 d " o~ono)-4-methylpiperidin-2-one (13) by reaction with polyphosphonc a ~ produces 1,2,3,4-tetrahydro-7-methoxy-9-methylpyrido[3,4-a]ind~176 (14) (A.Amone et al., Gazz., 1991, 121, 515). Me

MeO "~~

Me

o

(13)

!

H

MeO,

o

(14)

"H

274 (2) Pyrazoles, pyrazolines and pyrazolidines Phenylhydrazine reacts with 5-azido-2-furaldehyde to give at first the corresponding phenylhydrazone, but this loses nitrogen and ring opens to afford the phenylhydrazone (1) of 5-cyano-2-oxopent-3-enal. In the presence of a base, such as N,N-dimethylphenylamine, or triethylamine, this product recyclises to form 5-cyanomethyl-4-hydroxy-l-phenylpyrazole (2), or its tautomer (3) (F.Povazanec, J.Kovac and D.Hesek, Collect. Czech. Chem. Commun., 1980, 45, 150). PhNHNH2 N3

CHO

~

-N2

N3

ON.N.p,ONH---. ,O (1)

CH=NNHF

.---___. O (2)

(3)

Arylhydrazines combine with 2-cyano-3-ethoxybut-2-enethiamide (5) to afford the corresponding 3-arylhydrazinyl derivatives, but when these are heated with strong base they cyclise to 5-amino-l-aryl-3-methyl-4-thioformamidopyrazoles (6) (P.Giori et al., J. Het. Chem., 1985, 22, 1093). CSNH2 CSNH2 ArNHNH;Me~ B Me~ ~ ~ CN ~ N T " CN EtO ArNH "H

(4)

CSNH2 Me

NH2 N-N

(5)

,, Ar

A patent [O.Schalle and E.Klauke, Ger. Often., D.E. 3447211 (1986); C.A., 1984, 105, 152687d] describes a synthesis of 5-amino-l-aryl-3-cyanopyrazoles from the reactions of arylhydrazines with 2-cyano3-ethoxyacrylonitrile:

275 Ar- NHNH2 +

EtOCH=C(CN)2 NC

At-

NHNHCH=C(CN)2

NH2

y

~~N ~ N ` , Ar

When phenylhydrazine is heated under reflux with 3-cyanobenzopyran-4-one an intermediate iminohydrazine (6) is formed. This is tautomeric with the aminohydrazone (7). Prolonged heating of the tautomers causes opening of the chromone ring and recyclisation to 3-amino-4-(2-hydroxybenzoyl)- 1-phenylpyrazole (8) (C.Ghosh, D.K.Sinharoy and K.Mukhopadhyay, J. Chem. Soc., Perkin Trans. 1, 1979, 1964). O

( cm

PhNHNH2

O

O

NHNHPh

(6)

Ph NNHPh

0

(8)

NH2

0

NH2

(7)

Fused pyrones (9) when reacted with phenylhydrazine undergo ring opening to yield acyclic hydrazones (10), which recyclise to pyranylpyrazoles (11) and 3,5-diacylpyrazoles (12) (or their tautomers) (A.B.Saranovic, B.K.Razem and I.Susnik, Heterocycles, 1989, 29, 1559).

276 O

O

PhNHN PhNHNH2 ~

O

CO2Et

Me

O O

Me

CO2Et

(9) PhNHN

.•

Me

~CO2H CO2Et

0

(~o) Ph N"N

O

0 I

o

+

o

CO2Et

(11)

N-N

Ph ,,

CO2Et

(12)

o~-Formyloxiranes (13)react with phenylhydrazine in benzene solution to give 4-substituted 1-phenylpyrazoles (I.G.Tishchenko, I.F.Revinski and P.Nahar, Dokl. Akad. Nauk. BSSR, 1982, 26, 53). O R / ~/ \

CHO

PhNHNH2 ~

O R / V

Ph~N ~,~ H/ " . .

R

-H20 ----I~

Ph"

(13)

In another approach phenylhydrazones (14) can be reacted with N,N-dimethylformamide under Vilsmeir conditions to afford 3,4-disubstituted 1-phenylpyrazoles (R.A.Pawar and A.P.Borse, J. Indian Chem. Soc., 1989, 66, 203).

277 R

R

Me2CHO/POCI 3

R

R

==..=

N

"N Ph" "H

I

Ph

(14)

3,5-Dimethyl-4-phenylazo-l-(N-phenylthiocarbamoyl)pyrazole (15) can be prepared by heating 2,3,4-pentanetrione 3-phenylhydrazone with 1-phenylthiosemicarbazide in ethanol at reflux (R.Jain, S.Tyagi and S.Agrawal, J. Indian. Chem. Soc., 1981, 58, 813).

O

Me

PhNHN: ~ M e Me

~

NH2NHCSNHPh ._~N ~ PhN=N N "CSNHPh

O

Me

(15) In the presence of N,N-dimethylhydrazine and acetic acid 2,3,4-pentanetrione 3-arylhydrazones form bis(hydrazones) which cyclise to pyrazolium cations. These undergo N-demethylation in situ to give 4-arylazo-l,3,5-trimethylpyrazoles (H.V.Patel et al., Syn. Commun., 1992, 22, 3081). O

ArNHN: ~ ~ : : O

O

H2NNMe2 ~/~Me HAc ArNHN~ ~NNMe2 Me

278

HO Me Me

Me

Me

.~~ ArN=N

AcO N Me

Me

Me Me

N"

ArN=N

NI Me

Oxidation of bis(arylhydrazones) (16) of 3-methylpentane-2,4-dione with lead tetraacetate, or mercury(H) acetate, gives 1-aryl-3,4,5-trimethylpyrazoles (18). The reactions involve dehydrogenation of the conjugated enamine tautomers of the bishydrazones to yield cis-azohydrazones (17), which then cyclise with elimination of nitrogen and a molar equivalent of an arene (R.N.Butler and J.P.James, J. Chem. Soc., Perkin Trans. 1, 1982, 555).

Me .~NNHAr Me

Me ~NHNHA'o] Me ~ NNHAr Me

~ NNHAr ~ Me

Me . _ ~ N=NAr Me NNHAr Me

(16)

(17) Me

-----I~

Me

Me

+ Ar -ArH Me NNHAr

Me

N. Ar Me

-

(18)

Pyrolysis of the arylhydrazones of aliphatic aldehydes may give rise to

279 pyrazoles. Anilines and indoles are also produced. For example, the phenylhydrazone of butanal yields 5-methyl-1-phenylpyrazole, aniline, and 3-ethylindole (M.Tsuboi, Z.Takebe and I.Fujita, Nippon Kagaku Kaishi., 1989, 302). Me

H Me

Me

N"

+

I"H Ph

I Ph

H + C6H5NH2

Oxidation of the 4-nitrophenylhydrazone of furan-2-yl phenyl ketone with lead tetraacetate in the presence of boron trifluoride-diethyl etherate leads to 5-methyl-l-(4-nitrophenyl)-3-phenylfurano[3,2-c]pyrazole (R = Me) in 45% yield. 1-(4-Nitrophenyl)-3-phenylfurano[3,2-c]pyrazole (R = H) is also produced, but in only a trace amount (S.C.Kuo and S.C.Huang, Hua Hsueh., 1986, 44, 54; C.A., 1987, 106, 156342f). Ar H" N"

Pb(OAc)4

N

~_-

Ar NI R

N

BF3/Et20 Ph

Ph (Ar = 4-NO2C6H4)

Arylhydrazones of cyanoacetamide form 5-amino-4-(2- aryldiazene-l-yl)-3-hydroxypyrazoles when reacted with hydrazine (M.K.A.Ibrahim, M.E1-Moghayar and R.H.Mohamed, Indian J. Chem. Sect. B, 1987, 26B, 832).

280 NH 2

HO

H

2-Aryl-4,4-dimethyl-5-phenylpyrazol-3-ones are obtained from the intramolecular cyclisations of the arylhydrazones of ethyl 2,2-dimethyl-3-phenylpropan-3-onoate (H.G.Henning and A.Koppe, Z. Chem., 1987, 27, 367).

P"'o2Et

Ph v

N~ N

s \

H Ar

Ar

Various 4-arylhydrazono-5-phenylaminopyrazolin-3-ones (19) can be prepared by treating 5-phenylamino-2-pyrazolin-3-one, or a tautomer, with arenediazonium chlorides (F.A.Amer, A.E1-H.Harhash and M.A.NourEldin, Pak. J. Sci. Ind. Res. 1979, 22, 185).

O

ArN2CI

ArNHN

O

-

PhNH

sN " H

PhNH

"

(19) In addition to the formation of arylhydrazones, diphenylcyclopropenone is ring opened by reactions with arylhydrazines. However, the acyclic products recyclise to afford

281 1-aryl-4,5-diphenylpyrazolin-3(2H)-ones (20) (T.Toda et al., Heterocycles, 1987, 25, 79).

Ph Ph

I

ArNHNH2

L--o

I

O

Ph N ~ ' ~ _ ~ "

H

7-N, Ar

Ph

(20) R.Berthold [Ger. Often., D.E. 3,416,204 (1985); C.A., 1985, 104, 109628c] has disclosed that pyrazolones (22) are formed when sodium arylhydrazinylsulphonates (21) are heated at 95 ~ with an aqueous solution of 3-oxobutanamide.

O

J

NaO3S~tN-N~tH H

Ar

MeCOCH2CONH2~ H20

Me

(21)

" Ar (22)

Pyrazolines result from the oxidation of the 1,3-bis(arylhydrazones) (23) of 1,3-dicarbonyl compounds with either lead tetraacetate, or silver oxide (S.Stephanidou, Synthesis, 1985, 296). Me

Me

ArNHN NNHAr (23)

Me

[Ol

Me

N=NAr N-N % Ar

Another synthesis requires the reactions of phenylhydrazine with N-cinnamoylarylamines [ArNHOC(Ac)=CHAr] (N.K.Mandal, R.Sinha and K.P.Banerjee, J. Indian Chem. Soc., 1984, 61,979). Related work describes the syntheses of 3-heteroarylpyrazolines (25; R = furan-2-yl, thiophen-2-yl, or pyridin-2-yl) from the reactions of

282 phenylhydrazine with the corresponding 1-aryl-3-heteroarylpropenones (24) (S.P.Sachchar and A.K.Singh, J. Indian Chem. Soc., 1985, 62, 142; also see B.P.Singh et al., ibid., 1993, 69, 312).

Ar"~

R

PhNHNH2v-= A r ~ R N-N

0

Ph

(24)

(25)

The phenylhydrazone of benzaldehyde enters into cycloaddition reactions with N-arylmaleimides, when in the molar ratio 1"1, to give 5-aryl- 1,2,3,3a,4,5,6,6a-octahydro- 1,3-diphenylpyrr olo[3,4-c]pyrazole-4,6-diones (26) (Y.A.Ibrahim, S.E.Abdou and S.Selim, Heterocycles, 1982, 19, 819).

Ph N

'N I'H

Ph

O +

N - Ar

O

Ph

0

H-N

N-Ar

Ph

O (26)

When 4-carboxyphenylhydrazinium chloride is reacted with 4-methylpent-3-en-2-one 1-(4-carboxyphenyl)-4,5-dihydro- 3,5,5-trimethylpyrazole (27) is formed in 69% yield (M.S.Ventatesh and V.V.Nadkarny, J. Indian Chem. Soc., 1979, 56, 216). Sterically hindered pyrazolines (e.g. 28), act as scintillators [H.Guersten, Ger. Often., DE 4,023,860 (1990); C.A., 1992, 116, 151757]. They are synthesised from 2,6-disubstituted phenyl 3-(N,N-dimethylamino)propyl ketones through treatment with phenylhydrazine.

283

,

NHNH3Cll HC'

CO2H (27)

R PhNHNH2 ..~

Me 2

N..N Ph R (28)

Phenylhydrazine reacts with 2-cyano-3-ethoxyprop-2-enones (29) to afford 4-acyl-5-ethoxy-3-imino-l-phenylpyrazolidines (30), or their 3-aminopyrazoline tautomers (31) (H.G.McFadden and J.L.Huppatz, Austral. J. Chem., 1991, 44, 1263). R_

OEt

PhNHNH2

R

OEt Ph v

RCO

CN

RCON ~ L """IIJ NH

(29) EtO

"H

Ph

EtO

Ph

-EtOH

R RCO"

-H g NH (30)

R

r

RCO"

N-H \\ NH

(31)

284 3. Indazoles The 2-acetylphenylhydrazone (1) of ethyl N-(cyanoacetyl)carbamate hydrolyses and cyclises when heated with 20% hydrochloric acid to form 3-methylindazole. The starting material is prepared by diazotizing 2-aminoacetophenone and reacting the product with ethyl N-(cyanoacetyl)carbamate (J.Slouka, V.Bakarek and A.Lycka, Collect. Czech. Chem. Commun., 1982, 47, 1746). A simple synthesis of indazole-3-carboxylic acid involves treating phenylhydrazine with chloral hydrate and hydroxylamine hydrochloride in aqueous acid and heating the product with concentrated sulphuric acid (M.Sisti et al., J. Het. Chem., 1989, 26, 531). Diethyl 2-oxocyclohexane-l,4-dicarboxylate when reacted with phenylhydrazine in 50% ethanol yields 6-ethoxycarbonyl-3,3a,4,5,6,7-hexahydro-2-phenylindazol-3(2H)-one (2) (V.Skaric and V.Turjak-Zebic, J. Chem. Soc., Perkin Tram. 1, 1979, 2099). Me

Me

O

?. N2CI

CN

o

o

N. ~

CO2Et

N-H

CN

H

(1) Me r

4. Imidazoles 2-[(2-Phenylhydrazin-l-yl)formo]benzimidazole (2) is prepared by condensing ethyl (2-phenylhydrazin- 1-yl)glyoxalate (1) with 1,2-phenylenediamine at 150-180 ~ [P.A.Petyunin, N.M.Valyashko and A.M.Choudry, Farm. Zh. (Kiev), 1980, 66].

I

CO2Et

285

O

/

~~

N-N , ~ O

i CO2Et PhNHNH2

EtO2C

EtO2C

~

NH2

v

-NH2

PhNHNHCOCO2Et (1)

Ph

(2)

~

N ....CONHNHPh N

H (2)

(N-Arylamino)methyl phenyl ketones (3) react under aza-Wittig reactions to yield hydrazones (4). These products can be cyclised to imidazolinones (5) through treatment with phosgene (H.Gnichtel and M.Sinell, Ann., 1988, 919).

H i N

H !

Ph3P=NNHPh

NHph

R

Ar " y COPh (3)

(4) O

COCI2 v

I I

Ar. N,,~N ~ NHPh Ph

N (s)

5. Thiazoles and thiadiazoles Cyclocondensation of 1-chloro-l-(N-phenylhydrazono)propan-2-one (1)

286 with thiourea in ethanol gives 2-amino-4-methyl-5-(phenylazo)thiazole (2), and when this compound is treated with potassium thiocyanate it yields 2-acetyl-5-imino-4-phenyl-A 2-1,3,4-thiadiazoline (3) (N.F.Eweiss and A.Osman, J. Het. Chem., 1980, 17, 1713).

H Ph

.,N

(NH2)2C~~"

Ac "N

el

(1)

SCN

Ph

%

N-N

Me

Ph N-N

s, N

Ac

NH2

(e)

(3)

The N,N-diphenylhydrazones (4) react with chlorocarbonylsulphenyl chloride at 20-100 ~ to afford thiazolones (5). However, when the substrate contains a benzoyl group and the reaction is carded out at 0 ~ the 1,3-oxathiolone (6) is produced (C.H.Xi and G.Kollenz, Heterocycles, 1992, 34, 2293). R

CICOSCI 20-100~

j

H

Ph ~ N " H I N(Ph)2 (4)

CICOSCI ooc COPh R =

6. Thiatriazoles 3-(N-Benzylaminocarbonyl)-5-phenyl- 1,2,4,5-thiatriazole 1-oxide (2) is

287

R

Ph

S

>=o

Ph

N

Ph ~

I

II

N(Ph)2

,,,~O

>=o

S N

" N(Ph)2 (6)

(5)

formed when 2-benzyl-4-methoxy-l,2,5-thiadiazol-3-one 1-oxide (1) is reacted with phenylhydrazine (S.Karady et al., Tetrahedron Letters, 1985, 26, 6155).

MeO

H ~

S -N (1)

CONHCH2Ph

S-N ~CH2Ph

00

Ph ~N" ~ N/ ~

O'

(2)

7. Pyridazines Diethyl 2-c yano-3-methylpent-2-en- 1,5-dioate ( 1) couples with arenediazonium chlorides to yield intermediate hydrazones (2) which cyclise to 2-aryl-6-ethoxycarbonyl-4-cyano-5-methylpyridazin-3-(1H)-ones (3) (N.S.Ibrahim et al., Heterocycles, 1986, 24, 1219). 3-(N-Arylhydrazono)pentan-2,4-diones (4) when reacted with acetyl chloride, or acetic anhydride, in the presence of either concentrated sulphuric acid, or p-toluenesulphonic acid, form the corresponding N-acetyl derivatives (5), together with 3-acetyl-l-aryl-6-methyl-1H-pyridazin-4-ones (6) (H.V.Patel et al., Indian J. Chem. Sect. B., 1991, 30B, 932). 2-Aryl-2,3,5,6-tetrahydro-3,6-diphenylpyranopyridazin-8-ones (8) are obtained in two steps from the 2-(N-arylhydrazones) (7) of pentane-2,3,4-triones. First the benzylidene derivatives are formed through reactions with benzaldehyde in the presence of sodium hydroxide, and these products are then cyclised by heating them with acetic acid (H.V.Patel and P.S.Fernandes, Indian J. Chem. Soc. Sect. B., 1989, 28B, 167). Pentane-2,3,4-trione 3-(N-arylhydrazones) are deprotonated by sodium hydride and then N-acylated by chloroacetyl chloride to afford the

288 derivatives (9). In the presence of excess sodium hydride these cyclise to 3-acetyl- 1-aryl-5-chloro-4,5-dihydro-4-methylpyridazin-(5(1H)-ones (10). The same products are also formed if the starting hydrazones are reacted with chloroacetyl chloride in the presence of sulphuric acid, or 4-toluenesulphonic acid (H.V.Patel, Indian J. Chem. Sect. B, 1992, 31B, 273). 2,3,4,4a-Tetrahydro-2-phenylcyclopentano(c)pyridazine (11) is formed when the phenylhydrazone of 2-(2-chloroethyl)cyclopentanone is heated (B.Robinson and D.G.Hawkins, Chem. Ind., 1985, 697)

O NCi ' ~ CO2Et Me

ArN2CI,.~ ---9

CH2CO2Et

NC~ I I

OEt N"H" Ar N

Me~

O

(1) NC

N"

Ar

CO2Et (2)

v

Me

C02Et

(3) NNHAr O

O (4)

0

O Ac20 Aci ~ M e N Ac "N" H2SO4 I Ar (5)

A N~N~C

Me I

Ar (6)

289

MemO

Ph

PhCHO

Ar"~ "N / " ~ M 0

O

Ph

NaOH/H20 H

O

(7) HOAc

A

Ph.

~

O

Ar N ~ ~N~/~~,~

.,,Ph "*

O

(8)

~

H I

N"

N

"Ar

NaH

~176 Me

CICH2COCI

Me

N

~176 N"

Me

"Ar

Me (9)

Ar i

Nail

O,.

N,, N

Me

Me

(10)

Benzopyranopyridazinones (13) are synthesised through the cyclisation of the phenylhydrazones (12) of O-substituted 2-hydroxybenzaldehydes (K.Hajela and R.S.Kapil, Indian J. Chem., Sect. B., 1990, 29B, 683).

290

r

H,. Ph"

Ph" (11) OMe

O

' / " t ' ~ ~ " ~ ' ~ - - N ~ N ~ Ph

"N

"H

0

I (13) Ph

(12)

3-Acetyl-3,4-dihydro-4-hydroxycinnoline (15) is synthesised from ethyl 2-(N-phenylhydrazono)but-3-onoate (14) by treatment with aluminium trichloride (M.S.K.Youssef et al., Commun. Czech. Chem. Soc., 1991, 56, 1768).

~

EtO2C /~.COMe AICI3.~"~

OH

COMe

NSN I

H

8. Benzoxazines Thermolysis of ethyl 2-{N-[2-(allyloxy)phenyl]hydrazono}-2-azido acetate (1) in boiling benzene gives 1-ethoxycarbonyl-3,4,4a,5-tetrahydro-pyrimidino[4,5-c]-l,4-benzoxazine (2). The reaction involves initial formation of a nitrene intermediate, followed by intramolecular 1,4-cycloaddition (L.Geranti and G.Zecchi, Tetrahedron Letters, 1980, 21, 559).

291

CO2Et

CO2Et

N~N3

H i "N

N~N " I

-N 2 v

(2)

(i) 9. Triazoles and benzotriazoles

Oxidative cyclisation of the bis(N-arylhydrazones) of cyclohexan-l,2-dione leads to 2,4-diaryl-4,5,6,7-tetrahydrobenzotriazoles (R.N.Butler and J.P.James, J. Chem. Soc., Chem. Commun., 1983, 627).

~

NNHAr Pb(OAc)4 ~NN .,._ NNHAr

DCM

- Ar

N Ar

Related chemistry shows that tris(N-arylhydrazones) of cyclohexane-l,2,3-triones are also oxidised by lead tetraacetate to give fused cyclohexanotriazoles, but the products now retain one hydrazono unit (S.Lefpopoulou, S.Stephanidou and N.E.Alexandrou, J. Chem. Res. Synop., 1985, 82). 5-Dialkylamino-2-aryl-4-cyano-l,2,3-triazoles are obtained by the oxidative cyclisation of the amidines (1). The starting materials are themselves formed by treating the arylhydrazones of malononitrile with secondary amines. The related chloroimides (2) are converted into 4-amino-5-(N-arylhydrazono)- 1,2,5,6-tetrahydro-3-(pyridin- 1-yl)pyrid-2,6-dione chlorides by treatment with pyridine and Thorpe cyclisation (H.Sch~ifer et al., Monatsh. Chem., 1991, 122, 195).

292

NNHAr

N

Ar

NNHAr DCM/25~

NNHAr

NNHAr

(R = H, or Me;Ar = C6H4-CI-4,or CsH4-Me-4) ArN,,N ~CN R2NH H"

Ar N HN,,H~N (1)

ArNH,.N ~ CN~ CI O

C

CuSO 4pyridinAr.. ell~N,,CN~~ NIN

NC

N I H

NR2

pyridine ArNH"N ~

O

NR2

"H2

O

O CII

H

(2) Diazomethane adds to the N-acetylphenylhydrazone (3) to give 1- [(N-acetyl-N-phenyl)amino]-5,5-di(methoxycarbonyl)- 1,2,3-triazol-2-ine (4) in 92% yield. Treatment of this compound with trifluoroacetic acid generates 1- [(N-acetyl-N-phenyl)amino]-2,2-di(methoxycarbonyl)aziridine (5) (A.V.Prosyanik et al., Zh. Org. Khim., 1985, 21, 911).

Ac C.O2Me Ac CO2Me CH2N2 I N,,,~ CO2Me --------tI~ Ph ,, N~ Ph" N.. N-N (3)

(4)

CO2Me ~ /

N-N d" CO2Me

Ph

(5)

293 1,2,4-Triazoles are synthesised from N-benzyloxycarbonyl a-aminoacids by first esterification with methyl choroformate and triethylamine, and then reaction of the esters (6) with methyl 2-(N-phenylhydrazono)-2-[(triphenylphosphoranylidene)amino]acetate (7). Deprotection of the products (8) is achieved through successive hydrogenolysis and treatment with hydrogen chloride gas (L.Bruch6, L.Garanti and G.Zecchi, Synthesis, 1989, 399).

MeO2C /~ +

R MeO2C

NHZ

N

N - PPh3

-----t~

~N

' "Ph H

(6) MeO2C

(7)

..z N-,N~ =

R

Ph (8) (Z = benzyloxycarbonyl) 1,3-Diphenyl-5-vinyl-l,2,4-triazole (9) is synthesised in an excellent yield by the oxidation of the cycloadduct formed between the radical cation of 1-benzyl-2-phenylhydrazine and acrylonitrile. Electron transfer from the parent hydrazine is achieved by addition of the radical perchlorate salt of thianthrene, or the radical antimonyhexachloride of tris(2,4-dibromophenyl)amine. Evidence is presented to show that the radical cation of the hydrazine undergoes cycloaddition with the C~N bond of the nitrile and further oxidation leads to the triazoles. An alternative route, in which a nitrilimine is considered to be the reaction intermediate, is discounted because when 1,3-diphenylnitrilimine, generated from N-phenylbenzohydrazonoyl chloride and triethylamine (see next section), was reacted with acrylonitrile the product was not 1,3-diphenyl-5-vinyltriazole, but 5-cyano-l,3-diphenylcyanopyrazoline (10). This result complies with the accepted view that the dienophilic activity of the cyanide group is less than that of the vinyl group (H.J.Shine and A.K.M.Hoque, J. Org. Chem., 1988, 53, 4349).

294

Ph V +

N ,, NHPh +

N--

IO]

i,,,= r

~. Ph

f

N

N--

" N " Ph

(9)

+

Ph ~ N .

NHPh

-I.-

Ph " ~~N'N'/Ph \

CN

CN

(lo)

Arylhydrazines react with methyl 2,2,2-trifluoroethylimino ether to afford arylhydrazinylimines (11), which cyclise to 1,5-diaryl-3-trifluoromethyl-1,2,4-triazoles (12) when treated with aroyl chlorides (L.Czollner et al., Monatsh., 1988, 119, 349). 1,5-Diaryl-3-tbuty1-1,2,4-triazoles (14) arise when 1-(arylhydrazin-2-yl)-l-imino-2,2-dimethylpropanes (13) are reacted with araldehydes in boiling xylene during the course of 20 hours [J.P., 60 209 573 (1985); C.A., 1985, 104, 148884c].

295 Ar - NHNHC(CF3)=NH

ArNHNH2 + F3CC(OMe)=NH

(11)

Ar ArCOCI

N-N

v

(12) Ar H / N-N ,

H

Ar "

ArCHO ,

C(Me)3

z~

A

N -N C(Me)3

HN

(12) (13) Similarly, 5-amino-3-methylthio-l-phenyl-l,2,4-triazole (15) is formed when phenylhydrazine is reacted with the substituted guanidine (14) (R.Evers and E.Fisher, J. Prakt. Chem., 1985, 327, 609).

H2NyN~

O2N,,N

"sMe

SMe (14)

PhNHNH2

N-N t

Ph

MeS ~ ' ~ N/ ' ~ NH2 (15)

1,3,5-Trisubstituted 1,2,4-triazoles are available through the oxidation of N-alkylamide arylhydrazones (amidrazones) with either hydrogen peroxide, or potassium permanganate (B.I.Busykin and Z.A.Bredikhina, Synthesis, 1993, 59). The reaction of acetone phenylhydrazone with phenylisocyanate at 60 ~ for 15 hours gives an oil from which three compounds may be isolated: 2-[ 1-phenyl- 1-(N-phenylaminocarbonyl)hydrazono-2-yl] propane (16), 5,5-dimethyl-2,4-diphenyltriazolidin-3-one (17) and 5,5-dimethyl-2,4-diphenyl- 1-(N-phenylaminocarbonyl)triazolidin-3-one (18) (M.Heitmann and G.Zinner, Chem. Ztg., 1980, 104, 239). Presumably the hydrazone (16) is

296 formed first and cyclises to the triazolidinone (17), this then reacts with a second molecule of phenylisocyanate to furnish the third product (18).

Ar

H / "N - N

R~N

Ar [O ]

'~N - N

Ph

Ph

R~

I

H

Ar

H "N'- N\

Ar

AF

"N-N

~

N-N Ph

I

H

H

Me

Ph N-N

Me N - Ph J PhNHCO

Me

o I

Ph

(16)

(17) PhNHCO

Ph N-N

PhNCO

%

t=.=

M

N I

Ph (18)

Acetone arylhydrazones [ArNHN=C(Me).z] combine with acetyl isocyanate in toluene solution to gwe 4-acetyl-l-aryl-5,5-dimethyl-l,2,4-triazolidin-3-ones (19). These on acid hydrolysis ring open,

297 expel acetone, and cyclise again to give 2-aryl-5-methyl-l,2,4-triazolin-3(4H)-ones (20) (P.S.Ray and R.F.Hanh, J. Het. Chem., 1990, 27, 2017).

Ar _~,O Ar"N .! " ~ OH Ar O N H+/H20 .Me20 xN H-N N. ~ N ~ N N Me%e COMe H"'~ - H --N~COMe 2 OH O M e " ~ "H Me

Me

(19)

(20)

Semicarbazones (21) react with aqueous potassium hydroxide to give 1-aryl-3-hydroxy-l,2,4-triazoles (22), but thermal cyclisation in boiling xylene affords the isomeric 2-aryl-2,3-dihydro-l,2,4-triazol-3(H)-ones (23) (O.Tsuge, T.Hatta and R.Mizuguchi, Heterocycles, 1994, 38, 235).

Hx

~

,"%

Ar ..N

'~ O

(23)

N

A

ArNH

~O

,

,,N N xylene H ' ~ "H O (21)

KOH / H20

-~

Ar \N - ~k~:::: N,~I/N /

OH (22)

Heating N-(benzyl)benzenesulphonamide (C6H5SO2NHCH2C6Hs) with phosphorus trichloride at 170~ gives N-(0t-chlorobenzylidene)benzenesulphonimide [C6H.sSOEN=C(C1)Ph]. This reacts with ammonium thioisocyanate to gwe N-((z-isothiocyanatobenzylidene)benzenesulphonamide [C6HsSO2N=C(NCS)Ph], which is cyclised with phenylhydrazine in diethyl ether to yield 1,5-diphenyl-l,2,4-triazoline-3-thione (24) (G.Barnikow and R.Dieter, Z. Chem., 1980, 20, 97). Cyclohexanone phenylhydrazone, in dimethylformamide, is deprotonated by sodium hydride and the anion so formed can then be reacted with phenylthiocyanate to afford 5-spiro-cyclohexyl-2,4-diphenyl-l,2,4-triazolidine-3-thione (25) (G.L'abb6 and K.Allewaert, Bull. Soc. Chim., Belg., 1987, 96, 825).

298 S // Ph "'"~N ,,N ~ H I

Ph (24)

NNHPh

H Ph N .. N"

(i) Nail y

~ ~

(ii) PhCNS

Ph (25)

6-(2-Aminophenyl)-2,3,4,5-tetrahydro-l,2,4-triazine-3,5-dione (26) can be diazotized and coupled with ethylcyanoacetyl carbamate to give the hydrazone (27) (91%). When heated with concentrated hydrochloric acid this product cyclises to 2,3,4,6-tetrahydro-l,2,4-triazino[5,6-c]cinnolin-3one (28), whereas heating in aqueous base leads to 1-[1,2,4-triazine- (2H,4H)- 3,5- dione-5- yl]-2- [6-cyano- 1,2,4-triazine- (4H)- 3,5- dione-2-yl]benzene (29) (J.Slouka, Collect. Czech. Chem. Commun., 1979, 44, 2438). H

H

I

I

Ns

I

N

N"H

~

N,, H NHN=C(CN)CONHCO2Et

(26)

(27)

299 H

O

/

I N

N-H

N

O

"H

,.N

,

_CN

oJ--. i o

H

H

(28)

(29)

10. Benzotriazines 2-Acetylbenzenediazonium chloride combines with alkylamines (RCH2NH2; R=H, CN, or CO2Et) to give 3-(2-acetylphenyl)-l-alkyltriazenes (1) which tautomerise to 3-alkyl-4-hydroxymethyl-3,4-dihydrobenzotriazines (2). The latter easily dehydrate affording the corresponding 3-alkyl-4-methylene-3H-benzotriazines (3) (K.Vaughan et al., Can. J. Chem., 1985, 63, 2455). Me

Me

0

~ "~----

N . NHCH2R

OH

N"

(1)

N

(2)

-H20 ~

N~

"-

R

N

(3) Cyclohexanone 2-aminophenylhydrazone (4) is in tautomeric equilibrium with cyclohexane-3-spiro-l,2,3,4-tetrahydro-l,2,4-benzotriazine (5). The cyclic tautomer is oxidised in air to cyclohexane-3-spiro-3,4-di-

300 hydro-l,2,4-benzotriazine (6). The reverse reaction is achieved through catalytic hydrogenation over palladium on carbon (F.Sparatore and R.Cerri, J. Het. Chem., 1989, 16, 1001).

H I N N--

HI [~N,,N,.

NH2

H

(4)

O'

c N'N >

~'H2/Pd

N H

H

(5)

(6)

This is one example of a wider investigation which reveals that the 2-aminophenylhydrazones of aldehydes are easily oxidised in air to afford 3-substituted 1,2,4-benzotriazines (8). In the absence of oxygen, acids catalyse the formation of 2-substituted benzimidazoles (9) with loss of ammonia. It is suggested that both reactions proceed via 1,2,3,4tetrahydro-l,2,4-benzotriazines (7) (R.Cerri, A.Boido and F.Sparatore, ibid., 1979, 16, 1005).

[~

H I N"N~CHR NH2

H i [~N"N"H N I H (7)

02

~Nr

N

H (8)

301 H

H

I

N

I

H

(7)

H H

N I H

I

"NH 2 C+R " ~H

H

+ NH3 I

R

H

H

(9)

10. N-Arylhydrazonoyl halides and arylnitrilimines (arylnitrile imides)

(i) Synthesis (hydrazonoyl halides) Arylhydrazones of c~-ketoaldehydes (ArNHN=CHCOR), react with N-bromosuccinimide to afford (N-aryl)acetohydrazonoyl bromides [ArNHN=C(Br)COR]. The corresponding chlorides are formed if N-chlorosuccinimide is the reagent. Similarly nitration with nitric acid sulphuric acid mixtures affords the nitro analogues [ArNHN=C(NO2)COR] (K.C.Joshi, V.N.Pathak and S.Sharma, Org. Prep. Proced. Int., 1985, 17, 146). Nitrosobenzene and ethyl N,N-dibromoaminoacetate combine together to afford 2-(ethoxycarbonylmethyl)-l-phenyldiazene 1-oxide. This when treated with concentrated sulphuric acid rearranges to give a mixture of the phenylhydrazone (1) and its tautomer the phenylhydrazine (2). If the azoxy compound is reacted with hydrogen chloride then the product is ethyl 2-chloro-2-(phenylhydrazono)acetate (3) (O.A.Luk'yanov et al., Ivz. Akad. Nauk. SSSR., Ser. Khim., 1990, 352). O Ph NO

+

~ Br- N\

CO2Et

DCM

Ph

/--- COzEt

~N+~N ' I

Br

20~

O-

302

H2SO4

0 Ph ~ CO2Et N-N H H

OH Ph />--- CO2Et N-N / H (1)

(2)

CI Ph / ~ - CO2Et N-N / H (3) (ii) Reactions Hydrazonoyl halides readily afford nitrilimines under basic conditions and many of the reactions of hydrazonyl halides probably involve the initial formation of nitrilimines which then act as 1,3-dipolar species (see below). The spectra and kinetic behaviour of nitrilimines, generated photochemically from tetrazoles and from sydnones, have been studied (K.Bhattacharyya et al., J. Photochem., 1987, 36, 63; see also A.S.Shawali et al., Spectrochim. Acta, 1992, 42A, 1165). Diphenylnitrilimine (Ph CN+N-Ph), the ground state structure of which has a localized triple bond and a linear, or almost linear, array of CNN atoms, can be prepared by the photochemical irradiation of 2,5-diphenyltetrazole in polyvinylchloride (H.N.Toubro and A.Holm, J. Amer. Chem. Soc., 1980, 102, 2093). Alternatively, the nitrilimine can be obtained from the same substrate by thermolysis at 180 ~ It reacts with benzaldehyde phenylhydrazone to give 1,3,4,6-tetraphenyl- 1,2,4,5-tetraaza-2,5-hexadiene (1). This compound is said to isomerise to the bis(N-phenylhydrazone) (2) of benzil (B.I.Buzykin, and N.G.Gazetdinova, Izv. Akad. Nauk. SSSR, Ser. Khim., 1980, 1616).

PhN'N=C+Ph +

H,

PhCH=N" N,, Ph

PhNHN

Ph

---.

PhNHN ,.

Ph

PhNHN

Ph

---*

PhCH=N" " Ph (1)

(2)

303 Arylnitrilimines are implicated as reactive intermediates in many reactions which lead to heterocyclic products. Thus N-acylated phenylhydrazines can be used to generate 1,3-dipolar intermediates, which are trapped by alkenes and alkynes to produce pyrazolines and pyrazoles respectively (H.Wamhoff and M.Zahran, Synthesis, 1987, 876). The reactions employ a phosphorylating-dehydrophosphorylating reagent system comprising of triphenylphosphine-perchloroethene (a source of Ph3PC12), and triethylamine.

AF

Ar

Ph3PCI2

RC--CR

C"

R

Ar

I/

N

H"

"N" H I

Ph

N

",N+

Et3N

I

__

Ph_~

I

Ph

Another source of pyrazoles (4) is provided by the cycloaddition of 2,2-dicyanostyrene and the nitrilimine from the triethylamine promoted dehydrochlorination of the N-aryl-C-(phenylaminocarbonyl)formohydrazonoyl chlorides (3). Other compounds, such as deoxybenzoins, may be used in place of the styrene (H.M.Hassaneen et al., Org. Prep. Proced. Int., 1989, 119). The reaction of 1-[N-(2-nitrophenyl)hydrazono]-l-chloropropan-2-one (5, Ar = 2-O2NC6H4) with sodium ethoxide and ethylcyanocyanate yields 3-acetyl-5-amino-4-ethoxycarbonyl-l-(2-nitrophenyl)pyrazole (6). The hydrazononyl chloride (5) also reacts with acetylacetone, or with dibenzoylmethane, to give the corresponding 3-acetyl-4-acyl-l-(nitrophenyl)pyrazoles (7), which upon hydrazinolysis yield 7-methyl-2-(2-nitrophenyl)pyrazolo[3,4-d]pyridazines (8) (H.M.Hassaneen, A.O.Abdelhamid and A.S.Shawali, Heterocycles, 1982, 19, 319). Nitrilimines are also probably implicated in the formation of pyrazolo[3,4-b]pyridines and pyrrolo[3,4-c]pyrazoles when N-aryl-C-(chloroformyl)formohydrazonoyl chlorides are reacted with suitable precursors in the presence of bases (M.K.A.Ibrahim et al., J. Indian Chem. Soc., 1987, 64, 345).

304

PhNHCO

Et3N

N

~ "N"

Ar

PhNHCO + ~-=-- N - N

v

I

CI

Ar

H (3) PhNHCO

PhCH=C(CN) 2

Ph

-HCN I

Ar (4)

CI

NCCH2CO2Et

Ac ~ ' N N H A r NaOEt

EtO2C .

/

NH 2

~~~"XtN - Ar Ac ~

(5)

N

(6)

(ROC)2CH 2 ~ NaOEt R RCO

NH2NH2 ~ N N - Ar

N

-

Ar

N

Ac Me

(7)

(8) (Ar = 2-NO2C6H4; R = Me, or Ph)

A procedure which affords 4-acyl-2-aryl-5-(arylsulphonyl)pyrazoles (11) initially involves bromination of the hydrazones (9), to give N-aryl-C-(arylsulphonyl)formohydrazonoyl bromides (10). These are then reacted with 1,3-dicarbonyl compounds. Should potassium isothiocyanate

305 be used in place of the dicarbonyl reactants then the final products are thiadiazines (12) (H.M.Hassaneen et al., J. Het. Chem., 1985, 22, 395; see also A.S.Shawali et al., ibid., 1982, 19, 73). Ac

H

Br2/NaOAc

Br

H

RCOCH2CoRRCOx/~R

ArSO2..~ N,I~I ., Ar ------I~ ArSO2-'~N,, ~ "- Ar HOAc/Ac20 (9) (10)

~

"" ArSO2..~N, ~1.. Ar (11)

KSCN

NH

ArSO2"~N -N " Ar (12)

Again it seems probable that the reactions involve cycloadditions between the corresponding nitrilimines and the isothiocyanate ion, or the enolates. Similarly, other nitrilimines undergo cycloaddition reactions with 1,4-benzoquinones to produce both mono- and bis-adducts (13) and (14), respectively (N.G.Argyropoulos, D.Mentzafos and A.Terzis, J. Het. Chem., 1990, 27, 1983). N-Arylbenzohydrazonoyl bromides react with phenylethynecopper(I) to gwe the corresponding hydrazines (15, R = C-CPh), however, if 3-hydroxypropynecopper(I) is employed then 1-aryl-5-hydroxymethyl-3-phenylpyrazoles (16) are produced (L.Yu.Okhin, Zh.I.Orlova and L.V.Belousova, Khim. Gerot. Soedin., 1986, 856). 1,2,4-Triazoles (18) are synthesised through the oxidative cyclisation of C-aminohydrazones (17). The latter are themselves formed from N-arylbenzohydrazonoyl chlorides by reactions with alkylamines (B.I.Buzykin, Z.A.Bredikina and N.G.Gazetinova, Zh. Obshch. Khim., 1991, 61, 1034).

306

O 4-

R

O

-

PhN=N=CR +

N

v p

a

R' Ph

O

O (13)

R

O H

R

(14) H

p,_(

Ar N-N

R

t

'.

PhC=CCu Ph

Ph .Ar HOCH2C=CCu ~ N ,N- N H ~ I N

Br

"~Ar

HOCH2

(15)

(16)

CI NHCH2R ,~ RCH2NH 2,.,~ [O] ,._ ArNHN Ph v ArNHN Ph v (17)

R ~_N /~

Ar ~'N- N

Ph

(18)

Oxalodihydrazonyl dichlorides combine with sodium azide to afford the corresponding diazides, which upon reduction with lithium aluminiumhydride yield the diamines. When these are treated with acyl halides (RCOC1) cyclisation to bis(1,2,4-triazoles) occurs. The same products arise if the diazides are converted first into phosphinimes by reaction with triphenylphosphine, then hydrolysis to the diamines and, finally, treatment with acyl halides (A.S.Shawali et al., Tetrahedron, 1993,

307 49,2761).

ArNHN

CI

ArNHN ~

NaN3

/

N3

LAH y

CI ArNHN H2N

\\

NNHAr NH2

,v

N3

.coc,

"NNHAr

NHAr

Ar ,,_ ,, N

N ~.e,'R " Ar

R

Examples where nitrilimines add across the imine (C=N) bond are known, thus diphenylnitrilimine reacts with isoquinoline to form 3a,9b-dihydro-l,3-diphenyl-lH-naphtho[ 1,2-c][1,2,4]triazole (19). Similar additions of diarylnitrilimines to substituted pyridines yield 1,3-diaryl-3a,7b-dihydro-lH-benzo[c][1,2,4]triazoles (20) (L.Grubert et al., Liebig's Ann. Chem., 1992, 885). Ph N-N

N

PhC--N+N-Phv'= [~~~~N~

Ph

(19) Ar

N--N

C

ArC-N+NAr ,..-"-

i ~ j ~ N~

Ar

(2o) Diphenylnitrilimine, generated in situ from N-phenylbenzohydrazonoyl

308 49,2761).

ArNHN CI

CI \\

ArNHN ~/~ H2N

NNHAr

/

ArNHN ~

NaN3

NH2

~NHAr

"-

,/

N3

RCOCl ~--

N3

LAH

NHAr

Ar ,, . ,, N N \\ /~ R--

/

N ~.e/R "l

N / - - - ' ~ N " N " Ar

Examples where nitrilimnes add across the imine (C=N) bond are known, thus diphenylnitrilimine reacts with isoquinoline to form 3a,9b-dihydro-l,3-diphenyl-lH-naphtho[ 1,2-c][1,2,4]triazole (19). Similar additions of diarylnitrilimines to substituted pyfidines yield 1,3-diaryl-3a,7b-dihydro-lH-benzo[c][1,2,4]triazoles (20) (L.Grubert et al., Liebig's Ann. Chem., 1992, 885). Ph N--N N

Ph

PhC-N+N-Ph

(19) AF

N--N

N

ArC-=N+N-Ar

(20)

Diphenylnitrilimine, generated in situ from N-phenylbenzohydrazonoyl

309 chloride, adds to benzenesulphonyl isocyanate to produce a mixture of the oxadiazole (21) and the triazolinone (22) (M.Hedayatullah and M.Benji, Phosphorus Sulphur, 1987, 32, 163).

O

PhSO2-N

~ Ph

PhC-=N+=NPh + PhSO2NCO Ph

/

0

PhSO2 ~ N ~ N

(21) ~ Ph

Ph

(22) Benzaldehyde hydrazone and methyl 2-chloro-2-(phenylhydrazono)acetate condense together in the presence of triethylamine at 50 ~ to give the formazan (23). This reacts with phosgene to yield 4-benzylidenamino-5-methoxycarbonyl-2-phenyl-l,2,4-triazolin-3-one (24) (H.Ehrhardt, G.Heubach and M.Mildenberg, Liebig's Ann. Chem., 1982, 994). O PhSO2 -N ~~--~N-/~ ~Ph

PhC'=N+=NPh + PhSO2NCO Ph O

/ (23)

PhSO2 ~ N~,,N ~ Ph Ph

(24) N-Aryl-C-(ethoxycarbonyl)formohydrazonoyl chlorides cyclise on treatment with sodium ethoxide to produce a mixture of 2,5-diaryl-3,6-di(ethoxycarbonyl)-l,4-dihydro-l,2,4,5-tetrazines (25) and 2-aryl-5-ethoxycarbonyl-4-(arylhydrazono)pyrazol-3(4H)-ones (26) (M.O.Lozinskii et al., lzv. Akad. Nauk. SSSR., Ser. Khim., 1990, 2635).

310 CO2Et

Ar\ N-N

H/

NaOEt

N ~ N --Ar

N, N Ar ~"

\~--CI

I

CO2Et

I

+

I

CO2Et (25)

NNHAr

O~

II

CO2Et

N-N J Ar (26)

N-Phenyl-2,2,2-trifluoroacetohydrazonoyl bromide (27) reacts with potassium isothiocyanate, or with sodium isocyanate, to afford 2-imino-3-phenyl-5-trifluoromethyl- 1,3,4-thiadiazoline (28), or 2-phenyl-5-trifluoromethyl-l,2,4-triazolin-3-one (29), respectively. The first product is readily hydrolysed to the corresponding carbonyl compound: 3-phenyl-5-trifluoromethyl-l,3,4-thiadiazolin-2-one (K.Tanaka et al., J. Het. Chem., 1987, 24, 1391).

CF3

Ph tN-H

Br KNCS~// (27) ~ a N C O CF3N~_ ~

CF3

Nil

O

(28)

(29)

311 Cycloaddition of diphenylnitrilimine and tetrazol-5-yl-N-sulphonylimines leads to 2,4-diphenyl-5-(tetrazol-5-yl)-l,2,3,5-thiatriazole S-oxides (30) (R.N.Butler and G.A.O'Halloran, Chem. Ind., 1986, 750).

N', N .

Ph

N -N

N-N NSO

+ PhC=N+N-Ph

..-

N', N, I

R

I

R

N I

N I

S.--N (~' ~Ph (30)

5-Alkoxycarbonyl-l-arylamino-lH-tetrazoles (33) can be synthesised by the electrocyclisation of hydrazonylazides (32, Y = N 3) in contact with thionyl chloride. The starting materials are themselves formed by treating hydrazonyl chlorides (31, Y = C1) with sodium azide (L.Bruche, L.Garanti and G.Zecchi, Syn. Commun., 1992, 22, 309).

N ,-H 'N

X

CO2R

SOCI2 ~

N" 'N ~ CO2R N H ,bN ..N

X

Y = N3 (31)

Y (33)

(32)

R = Me or Et X = H, 4-NO 2, 2-COMe, 4-CI etc.

11. Substituted arylhydrazines and 1,2-diarylhydrazines (hydrazobenzenes)

(i) Synthesis tButyl arylhydroxamates (ArN(OH)COtBu) are used to synthesise 2-methyl-2-phenyl-l-arylhydrazines, by reacting them with N-methyl-

312 phenylamine at 80 ~ (G.Boche, F.Ferdinand and S.Schroeder, Ger. Often. D.E., 3,803,580 (1989); CA., 1990, 112, 55216m]. Alternatively, N-arylcarbamates (ArNHO2CR) can be used (G.Boche,. F.Bosold and S.Schroexler, Angew. Chem., 1988, 100, 965). 1,2-Diphenylhydrazines (ArNHNHAr) are conveniently prepared by the reduction of nitrobenzenes with formaldehyde/glucose in the presence of 1,4-naphthoquinone in 50% aqueous methanol at 50-55 ~ Sodium dodecylbenzenesulphonate is added as a phase-transfer catalyst [S.Yuan and S.Liu, CN 1,032,657 (1989); C.A., 1990, 113, 114802v]. Another system uses silica supported polyvinylpyridine polymer-palladium complexes as catalysts for the hydrogenation of azo, or nitro compounds, to hydrazoarenes (J.P.Mathew and M.Srinvasan, Polymer Internat., 1992, 29, 179). Tributyltin hydride is also an effective reagent for the reduction of azobenzenes to hydrazobenzenes (A.Alberti et al., J. Org. Chem., 1992, 57, 607). 2,4,6-Tricyano, or pentacyanoaryl halides (C1, or Br), undergo nucleophilic aromatic substitution by phenylhydrazine to give the corresponding polycyanoarylhydrazobenzenes. In related cases where two halogen atoms are present bishydrazo compounds are produced and if three halogen atoms are present in the starting materials these may all be replaced when the conditions are severe enough (e.g. 130 ~ 2 atm.). All the hydrazo compounds formed by these reactions, on oxidation with lead peroxide, give the corresponding azo derivatives (J.Rieser et al., Liebig's Ann. Chem., 1981, 1586). The phenylhydrazone of 2-oxomalonic acid adds hydroxylamine to give the hydroxyamino derivative (1, R - NHOH). This upon hydrogenation over a palladium catalyst yields 2-amino(2-phenylhydrazinyl)propanedioic acid (1, R = NH2) (A.A.Siddiqui, K.H.Khan, and Basheeruddin, Indian J. Chem. Sect. B, 1981, 20B, 1003).

CO2H PhNH.N.~-.~ CO2H

NH2OH ~

CO2H PhNHNH R--~

R=NHOH

CO2H (I)

Benzil and acetophenone undergo selective reduction by titanium(HI) chloride in aqueous solution to produce semidione radicals. These add to p-substituted arenediazonium tetrafluoroborates to yield azo derivatives (2), which in turn can be reduced to the corresponding hydrazines (3). Other

313 products are 1,1-diacyl-2-arylhydrazines (4) arising through rearrangement of the semidione-arylazo radical cations, prior to reduction (A.Clerici and O.Porta, J. Org. Chem., 1991, 56, 6813). Ph

k

o/I

/

R

Ti3+

Ph

R

0

ArN2BF4

O-H

~9

7g Ph \

//

0

R

Ph \

.+

Ti3+

\

R N=NAr OH

Ti3+

---~"

Ph \

R

/\ NHNHAr

II

0

OH

(3)

(2)

\/ N=N Ar OH

/

Ph

NHAr

0

COR

(4) (ii) Reactions

A mild oxidising agent for the conversion of hydrazobenzenes into azobenzenes is tetrabutylammoniumcerium(IV) nitrate (H.A.Muathen, Indian J. Chem. Sect. B, 1991, 30B, 522). Heating hydrazobenzene with potassium ethoxide at 300 ~ gives N-ethylaniline in 76% yield, however, if 1-phenyl-2-(4-pyridyl)hydrazine is reacted in this way, at the slightly lower temperature of 260 ~ 4-(N-ethylamino)pyridine is the only product (M.F.Marshalkin, V.A.Azimov and L.N.Yakhontov, Zh. Org. Khim., 1979, 15, 1781). Rhodium and ruthenium triphenylphosphine complexes [Rh(PPh3)3C1 and Ru(PPh3)3C12] catalyse hydrogen transfer from propan-2-ol to hydrazobenzene at 90-180 ~ to give acetone and aniline (90% yield) (B.M.Savchenko et al., lzv. Akad. Nauk. SSR., Ser. Khim., 1979, 2632). Hydrazobenzene reacts with diethoxy disulphide to give azobenzene in quantitative yield. The first step seems to be the formation of a N-ethoxy disulphide derivative (1) of hydrazobenzene which eliminates ethanol to

314 give an intermediate dithiadiazetine (2). This then expels sulphur releasing azobenzene (H.Kagani and S.Motoki, Bull. Chem. Soc. Jpn., 1979, 52, 3463). Ph~

IPh

H

H

EtOSSOEt

N-N

"--

Ph,, N _ N ,'Ph I

I

H S . SOEt

(1)

-EtOH h,,N_;,,Ph -Sn Ph~N Ph (2)

2-(2-Arylhydrazinyl)tropolones undergo benzidine-type rearrangements when heated with hydrochloric acid in ethanol at 50-60 ~ The products are 2-amino-5-(4-aminoaryl)tropolones (3), which on hydrolysis give 5-aryltropolones (4) (T.Nozoe et al., Chem. Letters, 1986, 1577).

0

0

ArNHNH.~~

H2N"~NHAr

(3)

(4) 12. Formazans

(i) Synthesis

3-Acetyl-5-aryl-l-(thiazol-2-yl)formazans (1) are formed when the arylhydrazones of pyruvaldehyde are reacted with 2-thiazolediazonium sulphate (L.V.Shmelev et al., Zh. Obsch. Khim., 1986, 56, 2393).

315

Ar,N,,H

N

I

+

(

Ar-N,,H ,,,J~S ~ N2)2SO4

,~

NI

COMe

II N

COMe (1)

5-Aryl-l-(2-methyltetrazol-5-yl)-3-phenylformazans (3) are prepared in 50-100% yields by the reactions of the 2-(2-methyltetrazol-5-yl)hydrazone (2) of benzaldehyde with arenediazonium chlorides (V.P.Shchipanov et al., Zh. Org. Khim., 1979, 15, 2207).

N=NAr Me

"

H (2)

Me ~

N

"N

,~ H

(3)

1,1",5,5'-Tetraphenyl-3,3"-biformazan (5) is prepared by reacting 3-formyl-l,5-diphenylformazan (4) with phenylhydrazine, followed by treatment of the product with benzenediazonium chloride. Dehydrogenation of the biformazan also causes rearrangement affording the tetrazol-5-yl betaine (6) (F.A.Neugebaur and H.Fischer, Chem. Ber., 1980, 113, 1226). Treating the biformazan (7) with paraformaldehyde and boron trifluoride diethyletherate in dichloromethane gives the bis(verdazylium) ion (8) which can be reduced by formaldehyde and ammonia in dimethylformamide to give the biradical 1,1',l,5,5'-tetraphenyl-3,3'-biverdazyl (9) (F.A.Neugebauer, H.Fischer and P.Meier, Chem. Ber., 1980, 113, 2049).

316 Ph Ph

"N"

H PhNHNH 2

i

N~N.~N~,Ph

i

Ph

(4) ~N"

,N

"H

H

I

N~N,~N." Ph

PhN2CI

Ph

-N..N

N'~N" Ph

N-N

Ph

N

i

N

"H

~N"

N-N % Ph

"N"

H

I

H PhNHNH 2

i

Ph

(6)

(5) Ph

Ph

t

x>- C'-

,+ N Ph"

Ph

Wr

CHO Ph

H "N" i N~ N

NN~y N .. N

N,~N.~NS Ph CHO

~

Ph

i

N

Ph J "H (4) Ph

"N"

H

I

N,~N~NsPh

PhN2CI

Ph

"N..N ,+

N , ~ N~,,N-- ph i

Ph"

N

Ph

N

N-N N -

/

Ph

Nx Ph

"H

(5)

(6)

A betaine (12) can be formed through the O-demethylation of 5-(4-methoxyphenyl)-2,3-diphenyltetrazolium tetrafluoroborate (11) and

317

Ph

Ph

Ph N-N

H/ N-N

Ph

HCHO

N--N

\>__<\

/

N-N

N -N

N - N '+

< ,>--<'

H /

N-N

(7)

Ph

Ph

Ph

(8) Ph

HCHO/NH 3

Ph

~N+_'N

Ph N-N"

N-N

N-N

N-N

< Ph

> Ph

(9)

treatment of the product with base. The tetrazolium salt is synthesised from the phenylhydrazone of 4-methoxylbenzaldehyde by reaction with the benzenediazonium cation. This affords 1,5-diphenyl-3-(4-methoxyphenyl)formazan (10) which can be oxidatively cyclised to the salt (12) with N-bromosuccinimide in the presence of sodium fluoroborate (S.Araki, N.Aoyama and Y.Butsugan, Tetrahedron Letters, 1987, 28, 4289). New formazans (13, R = H, 4-C1, 4-NO 2, or 4-CO2H) showing good virucidal activity are prepared from the 4-nitrophenylhydrazones of 4-methoxy-3-nitrobenzaldehyde and arenediazonium chlorides.

OMe

OMe

OMe PhN2+X

NBS/NaBF 4

.

Ph H" N,- N , .N

Ph

N ,,. N "Ph

"H

(1o)

N~

Ph

N

~i_~u , \

(i~)

Ph

318 O_

(i) BBr 3 (12) (ii) NaOH

Ph

/

h_ z "Ph

H

H

I

I

N

NO2

4-R-C6H4N2CI

I N

;I

-=

Me

NO2

NO2

NO2

"0.

R

(13)

Multidentate formazans of the type (15) can be prepared from bis(benzenediazonium) ethers (14) and sodium cyanoacetate in the presence of copper(II) ion in aqueous solution of pH <1. In addition to the two examples shown below, another bearing a OCH2CH2OCH2CH20 bridge between the two benzene rings has also been synthesised. These compounds are selective chelating agents for alkali metals (V.M.Dziomko et al., Zh. Obshch. Khim., 1981, 51, 2324). Mixed aryl heteroarylformazans [HetC(N=NAr)=NNHPh] are synthesised by treating heteroarylformylhydrazones (HetCH=NNHPh) with arenediazonium chlorides (D.T.Nguyen, T.D.Ha and T.K.D.Lai, Tap. Chi. Hoa. Hoc., 1988, 26, 31; C.A., 1991, 115, 135852t). Oxidation of phenylhydrazine by selenium dioxide in hydrochloric acid containing copper(I) chloride gives chlorobenzene. In absolute ethanol selenium dioxide affords the formazan [PhNHN=C(Me)N=NPh], which on continued oxidation gives 5-methyl-2,3-diphenyltetrazolium hydrogen-

319 selenite (16) (Yu.A.Sedov, Khim. Geterot. Soedin., 1983, 265). CN

N2CI

N ~'N ~'~'~ N N--H

0~0 (14)

O~n o (n = 2or3)

Ph

(15)

Ph ~N+"N"

N~

N HSeO 3-

/ Me (16) (ii) Reactions and physical properties

1-Aryl-3-benzyl-5-(4,6-diphenylpyrimidin-2-yl)formazans form complexes with several divalent metal ions (e.g. Cu(II), Ni(II), Co(II), and Hg(II)) (G.N.Lipunova et al., Zh. Obshch. Khim., 1983, 53, 178). Other formazans containing 3,5-dialkypyrazole units behave similarly and produce complexes with Pd(II), Ni(II), and Cu(II) salts (V.M.Dziomko, et al., Khim. Geterot. Soedin., 1984, 106). Formazans (2-HO-ArN=NC(R)=NNHAr-OH-2) bearing two 2-hydroxylated aryl groups form complexes with Yb(III) and Ce(III) ions. Some properties of these complexes (kmax etc.) have been compiled (I.A.Shikhova, M.I.Ermakova and N.I.Lathosh, Tr. Inst. Khim. Ural. Nauchn. Tsentr. Akad. Nauk. SSSR., 1978, 37, 63). X-Ray crystal analyses of the configurational isomers of 1,5-diaryl-3-(methylthio)formazans has established their structures. These results have allowed the origins of their visible spectra to be interpreted

320 (A.T.Hutton and H.M.N.H.Irving, J. Chem. Soc., Chem. Commun., 1980, 763). 2,3,5-Triaryltetrazolium chlorides (1) are synthesised from triarylformazans through reactions with thionyl chloride in benzene (S.A.Belyakov, Zh. Org., Khim., 1989, 25, 2252). AF

Ar ~ N ~"N,,,y~N Ar

"N"

H

SOCI2 v

I

Ph Ph

/

'Ar

(1)

13. Arylazides (i) Reactions The photolysis of phenylazide generates phenylnitrene which is in equilibrium with benzazirine and didehydroazepine. If potassium acetate in the presence of a catalytic amount of 18-crown-6 is added 2-acetoxy-l-azacyclohepta-l,4,6-triene is obtained as a transient product which rapidly hydrolyses to 3H-azepin-2-one. A different reaction course operates when potassium cyanide is added, now the product is a zwitterionic triazene (Scheme 1) (R.Colman et al., Chem. Ind., 1981, 249). However, during the photolysis of 4,4'-di(azido)biphenyl in an argon matrix at low-temperatures (15-20 K) the dinitrene is produced, a didehydroazepinone intermediate is not involved. Evidence for the dinitrene is obtained by using 15N-labelled startin~ material which in the presence of carbon monoxide led to labelled 4,4-di(isocyanato)biphenyl (T.Ohana, M.Kaise and A.Yabe, Chem. Lett., 1992, 1397). When arylazides are irradiated in aqueous conditions azepin-2-ones are formed, probably though the intermediacy of benzazirines (Scheme 2), but it should be noted that in some cases the products may not be those anticipated. For example, the photoinduced ring expansion of 2-azidobenzonitrile in 1:1 tetrahydrofuran:water gives 30% of the expected product 3-cyano-3H-azepin-2(1H)-one and 16% of the unexpected product 7-cyano-3H-azepin-2(1H)-one (K.Lamara et al., Tetrahedron, 1994, 50, 5515).

321

PhN3

KON1

r

MeCN 18-crown-6

PhN

[~

N

I KOAc

PhN=N-N-CNK +

OAc

j.-

H20

~~O_ H Scheme1 N3

N3

CO

OCN~

~

:N

N"

NCO

The cathodic reduction of 4-nitroazidobenzene gives first the radical anion (4-O2NC6H4N3"-), which has a very short half life, and then the nitrene radical anion (4-O2NC6HnN'-). The latter is rather more stable than its partner, but it rapidly dimerises to the dianion

322

N3

-N2

H Scheme 2

CN

.hv N3

H20/THF

.o

+

H

H CN

[(4-O2NC6H4N=NC6H4NO2)2-]. In dimethylformamide solution the nitrene radical anion may abstract a hydrogen atom from the solvent to form the anion (4-O2NC6HnNH), and also react with the solvent to give the anion of the corresponding N- (4-nitrophenyl)-N',N'-dimethylurea (4-O2NC6HnN-CONMe 2) (D.Herbranson and M.D.Hawley, J. Org. Chem., 1990, 55, 4297). 4-Azidobenzaldehydes are reduced to the corresponding 4-aminobenzaldehydes, plus their diethoxyacetals by treatment with tin(II) chloride in ethyl acetate/ethanol. Nitro groups are not reduced under these conditions (K.R.Gee and J.F.W.Keana, Syn. Commun., 1993, 23, 357). Arylamines are produced through the reductive amination of arylazides in contact with tetracarbonylhydridoferrate under an atmosphere of carbon monoxide. Yields range from 70-100% (S.C.Shim and K.N.Choi, TetrahedronLetters, 1985, 26, 3277).

(ii) Uses in heterocyclic syntheses Arylazides undergo 1,3-dipolar addition reactions with 1-acyl-2-phenylethynes to afford 5-acyl-4-phenyl-l,2,3-triazoles (F.A.E1 R.Fouli, et al., Acta Chim. Hung., 1988, 125, 785). The reaction of 2-azidobenzaldehyde with triphenylphosphine gives the corresponding aza-ylide (1) and the 2-(N-benzylidenamino)indazole (4). The triazeno derivative is also obtained, and presumably it is the ketene tautomer (2) of this compound which undergoes an intramolecular cyclisation to give the intermediate indazole (3). This then enters into an aza-Wittig reaction with the aza-ylide to afford the indazole (4) (P.Molina et al., Tetrahedron Letters, 1991, 32, 2521).

323

[~

N - N - N - PPh 3 Nc~ POPh3 CHO (1) H

H

I

I

N - N - N - PPh 3

~ N - N" PPh 3

0

O

(2)

(3)

H

(2)

I

(3) O

(4)

/ Ph3P - N

Arylazides when heated in boiling phenylisocyanate yield 1,3-dihydro-l-phenyl-3-phenylcarbamoylbenzimidazol-2-ones (6), and azo compounds. In some cases, where R = acetyl, methoxycarbonyl, or carbonitrile, work-up of the reaction mixtures with methanol gives methyl N-arylcarbamates (7). The initial step is assumed to be the formation of an azirine (5) which then reacts with phenylisocyanate to give zwitterionic species which either cyclise to the benzimidazole, or fragment into arylisocyanates. These last compounds then react with methanol to form the methyl carbamates (7) (D.I.Patel and R.K.Smalley, J. Chem. Soc., Perkin Trans. 1, 1984, 2587).

324

"'CL ---'" N3

"N2

P,NCO R

O

R

Ph

(5)

NCONHPh

NCO P j: 0

i1=.,= v

~

+ ~ Ph ~r ,~~NCO R

I

0

R (6) ,,~~

--'------i~"

N Ph

NHCO2Me

R

(7) 2-Azidobiphenyl (8) treated with aluminium trichloride in dichloromethane at room temperature gives carbazole (9) in 83% yield. Under the same conditions (2-azidophenyl)phenylmethane (10) affords 9,10-dihydroacridine (11) in 89% yield (H.Takeuchi et al., J. Chem. Soc., Chem. Commun., 1985, 287). Arylazides combine with phospha-alkenes to generate dihydrotriazaphospholes (F.Bickelhaupt et al., Tetrahedron, 1984, 40, 991). When these products contain a potential leaving group the corresponding triazaphospholes are produced. Thus a reaction of bis(trimethylsilyl)chlorophosphaethene (12) with phenylazide gives first the triazophospholine (13), and then 2-phenyl-5-trimethylsilyl- 1,2,3,4-triazaphosphole (14) (L.K.Yeung, Y.C.Yeung and R.Carr6 (J. Chem. Soc., Chem. Commun., 1984, 1640).

325

AICI3/DCM

HI

\N3 (8)

(9)

I

H

(lo) /CI P

PhN3 SiMe3 ~

SiMe3 (12)

(11) Ph ~ N" N~ N ;P-~ CI

Ph ~ N .N~N SiMe3

~P=Jx

SiMe3 (13)

SiMe 3 (14)

1-Azido-2-(phenylthio)-9,10-anthraquinone (16) is prepared by diazotisation of 1-amino-2-(phenylthio)-9,10-anthraquinone (15) and treatment of the diazonium salt with sodium azide. When this product is heated at reflux in toluene, or irradiated in dioxane with ultraviolet light, the fused isoxazole is formed. An increase in temperature by changing to dimethylformamide as the solvent in the thermal reaction, or prolonged irradiation in the photochemical case, both lead to the formation of the naphthophenothiazine (17) (L.M.Gornostaev, V.A.Levdanski and E.P.Fokin, Zh. Org. Chim., 1979, 15, 1692). An essentially similar cyclisation occurs when 1-(arylazo)-8-azido-2-hydroxynaphthalenes (18) are heated or photolysed. In this case the products are 2-(arylamino)benzo[c,d]indazol-3(2H)-ones (19) (P.C.Montevecchi and P.Spagnolo, J. Org. Chem., 1982, 47, 1996).

326 O

~

0 [ ~ ~ SP 'h N

N3

~'~S" ph

0 (15)

(16)

0

(~7) Ar

Ar

N-H N-N 1

l

N, N'~N OH

(18)

-N2 ~

~

/~0 (19)

N-(2-Azidobenzoyl)phenylhydrazine (20) is oxidised by lead tetraacetate in acetonitrile to yield the benzoylazo compound (21), which on thermolysis in boiling xylene gives the azoanthranil (22). Thermal rearrangement of the azoanthranil in 2-dichlorobenzene affords 3-phenyl-l,2,3-benzotriazin-4-one (23) (R.K.Smalley, R.H.Smith and H.Suschitzky, Tetrahedron Letters, 1979, 4687. For related work see M.A.Ardakani, R.K.Smalley and R.H.Smith, J. Chem. Soc., Perkin Trans. 1, 1983, 2501).

327 0

O

H

LLN ' "Ph

Pb(OAc)4

N

~,N

"Ph

H

N3

(20)

Ph

N~

I

(21) O

N

A

"Ph

(22) 0

I

N

(23) Arylazides on heating (100-170 ~ with sodium azide in dimethylsulphoxide, give arylamines [F.Babudri, L.DiNunno and S.F.Flori, Chim. Ind. (Milan), 1980, 62, 755]. Reduction to the corresponding anilines occurs when arylazides are treated with (triphenylphosphine)copper(I) tetrafluoroborate in chloroform at room temperature (S.J.Clarke, G.W.J.Fleet and E.M.lrving, J. Chem. Res., Synop. 1981, 17).

14. Aryltriazenes (diazoamino compounds) (i) Biological importance Certain 1-aryl-3-[2-(2-chloroethylthio)ethyl]triazenes (ArNHN=NCH 2CH2SCH2CH2C1) are known to exhibit cytotoxic properties similar to those of other sulphur mustards (R.Singh, Indian Chem. Soc., 1984, 23B, 1088). 3,3-Dialkyl-l-aryl-triazenes are carcinogenic, but some also show antineoplastic activity against rodent tumours. In mammals 3,3-di-

328 methyl-l-phenyltriazene is oxidatively metabolised into 3-methyl-l-phenyltriazene and formaldehyde, and it seems likely that this is a prerequisite for useful anticancer activity in man. If so drugs based upon this prototype can only be of value to patients with competent hepatic function, capable of activating the parent triazine through oxidation (M.D.Treadgill and A.Gescher, Pharmacol. Ther., 1987, 32, 191; and references cited therein). Since the first step in the metabolism of 3,3-dimethyltriazenes is conversion into 3-methyl-3-(hydroxymethyl)triazenes the question has been raised as to whether these products are independent cytotoxins. New work shows that such compounds are unstable in water at pH 7.4 undergoing dehydroxymethylation. This occurs sufficiently fast to indicate that 3-methyl-3-(hydroxymethyl)triazenes are not themselves antitumour agents, although it is possible that they react with nucleophiles to give more stable derivatives which are transported to the active sites. Hydrolysis could then release the parent compounds where they could act as alkylating agents foi macromolecules (R.J.Simmonds et al., J. Chem. Soc., Perkin 2, 1993, 1399). It is also noted that 3-acyl-3-alkyl-l-aryltriazenes undergo efficient general base-catalysed deacylation to liberate the corresponding cytotoxic 3-alkyl-l-aryltriazenes (J.Iley et al., J. Chem. Res.(S), 1989, 162). This may have significance if 3-alkyl-3-formyl-l-aryltriazenes are proved to be intermediates formed from 3,3-dialkyl-l-aryltriazenes in vivo. (ii) Synthesis

The traditional approach to aryltriazenes is through a coupling reaction between a arenediazonium salt and a primary, or a secondary, aliphatic amine. However, pentaazadienes may also form when primary aliphatic amines are reacted with arenediazonium salts not bearing electron withdrawing groups (T.P.Ahern and K.Vaughan, J. Chem. Soc., Chem. Commun., 1973, 701). This does not seem to be a problem, however, when arenediazonium chlorides (R-C6HnN2C1; R = H, 4-Me, 4-MeO) are reacted with pyrrolidine. Here the appropriate triazenes (RCHN=NX; X = pyrrolidin-l-yl) are obtained in good yields (N.I.Foster et al., Synthesis, 1980, 572). Similarly, 1-(3-carboxy-5-methylphenyl)-3,3-dimethyltriazene and related compounds are prepared by diazotizing the appropriately anilines and reacting the products with dimethylamine (F.Comea et al., Rev. Roum. Chim., 1980, 26, 701). In a further example of this type 1,3-thiazolidines can be coupled with arenediazonium tetrafluoroborates in aqueous acetone solution to yield the corresponding triazenes (K.Vaughan et al., Can. J. Chem., 1988, 66, 2487).

329

H .. N ~

S

ArN2BF4

\ i

Ar - N .=

/"" S

'~- N%~j

However, if 2-acetylbenzenediazonium chloride is reacted with anilines (ArNH2; Ar = Ph, 4-MeC6H4, C6HsCH2) the corresponding aryltriazenes (1) are produced, but these may cyclise to 3-hydroxybenzotriazines (2) (S.Treppendahl and P.Jakobsen, Acta Chem. Scand., Ser. B, 1984, B38, 185).

COMe

~

HO [~N~

Me

NN"

Ar

N=NNHAr (1)

(2)

When the terminal nitrogen atom of the aryltriazene is acylated cyclisation cannot occur and thus acylated aryltriazenes can be prepared from diazonium salts and amides. For example, 4-methylaniline, when diazotized and treated with acetamide in sodium hydroxide solution, gives 3-acetyl-l-(4-methylphenyl)triazene (S.Treppendahl, P.Jakobsen and J.Wieczorkowski, Acta Chem. Scand., Ser. B., 1983, B37, 155). In a different approach it has been shown that when arylazides (4-RC6HnN3; R = NO 2, CN, COMe etc.) are treated with potassium cyanide and then with dimethyl sulphate, in the presence of 18-crown-6, mixtures of 1- and 3-methyl-l-aryltriazenyl-3-carbonitriles [4-RC6H4N(Me)N=NCN and 4-RC6H4 N=NN(Me)CN] are formed. If dimethyl sulphoxide in methanol is used in place of dimethyl sulphate only 1-methylated products are obtained (M.Tanno, S.Sueyoshi and S.Kamiya, Chem. Pharm. Bull., 1982, 30, 3125). Bromoanilines can be diazotised and then reacted with pyrrolidine to give the corresponding triazenes. These products serve as useful substrates in lithiation reactions, during which the bromine atom is displaced giving lithiated derivatives. These undergo regioselective reactions with electrophiles, such as carbon dioxide, ketones, diphenyl disulphide, and trimethylsilyl chloride. Hydrolysis then affords the appropriately substituted arylamine.

330 Other arylamines are similarly converted into pyrrolidinotriazenes and these undergo Sandmeyer reactions with copper(I) chloride, or bromide, to yield chloro, or bromoarenes, respectively (M.L.Gross, D.H.Blank and W.M.Welch, J. Org. Chem., 1993, 58, 2104).

{~

NO /

NH2

(i) NaNO 2 / HCI

~

(ii) pyrrolidine

L ~ Br

Br

~

NO N'N H20/~,.~ /

H+

E

{~

N: N

(i) SBuLi (ii) E +

~

NH 2

E

NO /

N'N

CuX / HX

~

X

X = CI or Br

Aryltriazenes [ArN=NN(Me)CH2OH] can be prepared by treating arenediazonium tetrafluoroborates (4-R C6H4N2+BF4-; R = C1, Br, CN, Ac, EtO2C, NO2) with aqueous formaldehyde and methylamine (M.Julliard, G.Vermin, and J.Metzger, Synthesis, 1980, 116). These products can sometimes be isolated in the form of their O-acetyl derivatives, however, the products may be contaminated with other compounds. These include dimers and cyclic products (G.F.Kola and

331 M.Schendzielorz, Z. Naturforsch. C. Biosci., 1987, 42, 41). 1,3-Diaryltriazenes are obtained through the reactions of arylisocyanates with tetraethylammonium nitrite. The mechanism is suggested to be as follows (N.P.Botting and B.C.Challis, J. Chem. Soc., Chem. Commun., 1989, 1585):

Ar"

N~

O O"

O Ar N.J../~..._\ ~

0-. ,'O "N

O-N"

-CO2

~

Ar

ArN=C=O

At- N ~., IIBID O I~1

~

Ar

"N- N Ar " N - % O

_GO2

"N I!

"N-i Ar

Ar

"N

H+

II

r

N

"N .,H !

Ar

Arylhydrazones of glyoxal (ArNHN=CCHO; Ar=Ph, C6H4NO2-4, C6H4C1-4, C6H4Br-4) react with aniline to yield the corresponding triazenes (3). Spectroscopic data indicate that such compounds adopt a conformation which allows intramolecular hydrogen bonding (G.V.Shandurenko, G.V.Auramenko and B.I.Stepanov, Zh. Org. Khim., 1980, 16, 751).

N N. Ar" "H'" Ph (3)

Nitrosobenzene condenses with N-ethoxycarbonylhydrazine to give 3-ethoxycarbonyl- 1-phenyltriazene (PhN=NNHCO2Et) (S.G.Zlotin, O.V.Prokshits and O.A.Luk'yanov, lvz. Akad. Nauk. SSSR., Ser. Khim.,

332 1990, 1197). Other derivatives are obtainable through the manipulation of groups in the side chains of pre-sythesised triazenes, thus 1-aryl-3-[(aryloxy)methyl]-3-methyltriazenes [ArN=NN(Me)CH2OAr] are obtained by the reactions of 3-acetoxymethyl-l-aryl-3-methyltriazenes [ArN=NN(Me)CH 2OAc] with phenols in dry chloroform. The same products can be prepared if phenolates salts are used instead of the phenols, but now isomeric 1-aryl-3- [(hydroxyaryl)methyl]-3-methyltriazenes are also formed, illustrating the ambident nature of the nucleophilic phenate anion (M.P.Merrin et al., Can. J. Chem., 1992, 70, 144). Nitroso compounds react with arylhydrazines (4) to give hydroxylamines (5) and the N-oxides of triazenes (6) (K.Kano, M.Koga and J.P.Anselme, Bull. Soc. Chim., Belg., 1987, 96, 137). ArNH(R)NH2 + R'NO (4)

R'NHOH + R'N(O)=NN(R)Ar (5)

(6)

(R = Alkyl; R'= Ar)

When arenediazonium salts are reacted with two molar equivalents of 2-oximinopropane aryltriazenes (7) are produced in which two units of the original oxime are incorporated into the structure of the product (P.R.N.Nizamuddin, J. Indian Chem. Soc., 1986, 63, 252).

O~ N

..f. o' 9

N - Ar _1~~

H (7) 1-Phenyl-3,3-dimethyltriazene-2-oxide is prepared by reacting N-nitrodimethylamine with aniline-N,N-dimagnesium bromide (E.T.Apasov et al., Ivz. Akad. Nauk. SSSR., Ser. Khim., 1991, 1450).

333

(iii) Reactions 1-(t~-Cyanobenzylidene)-3-phenyitriazene exhibits strong electrophilic character and reacts with ammonia and amines to give a variety of products. However, it seems likely that these compounds all form through a common intermediate: the zwitterion (1), which may either cyclise to the triazole (2), or eliminate hydrogen cyanide to yield 1-(t~-aminobenzylidene)-l-phenyltriazenes (3). Loss of nitrogen from the triazole allows the formation of a second zwitterion (4), or its equivalent, which in the case where 1R = R = alkyl adds hydrogen cyanide to yield nitriles (e.g. 5). ff 1R = H tautomerism is possible affording dimines (6) (P.A.S.Smith and G.D.Mendenhall, J. Org. Chem., 1990, 55, 3362).

tPh R,RINH Ph R,R

N~, i~/'/' Ph

NC -

4

1R,RN

N -N

Ph

(2)

N~, Ph (4)

.A

cN RI= R = Me

Me2N , ~ N Ph H2N (5)

N',ph

Ph

>=_., (3)

,R _N2 J

(I)

Ph

R,RN

Ph ',~ N,, ,N

N,,

RI=H~

Ph N Ph

H2N

(6)

Although the rearrangement of diazoaminoarenes (ArN=NNHAr) to aminoazoarenes (NH2Ar-ArNH2) under acidic conditions is an extremely well known process, the mechanism of the reaction has been re-examined. However, the results of this new study are consistent with the earlier conclusion that there is an initial pre-equilibration forming the

334 corresponding amine and diazonium salt. This is followed by a rate limiting reaction of the diazonium cation at a C-atom of the amine (R.P.Kelly, J.R.Penton and H.Zollinger, Helv. Chim. Acta, 1982, 65, 122). Aryltriazene N-oxides (ArNHN=N(O)Ph) form stable 1:1 charge transfer complexes with tetrachloroethene (A.M.N.E1Din et al., Bull. Chem. Soc. Japan, 1992, 65, 553). The parent compounds can be synthesised from arenediazonium tetrafluoroborates and oximes (K.Vaughan and D.E.V.Wilman, J. Chem. Res. Synop., 1991, 294). Similar complexes are formed between aryltriazene N-oxides and picric acid [D.N.Purohit, Cienc. Cult. (San Paulo), 1985, 37, 1655]. Under appropriate conditions aryltriazenes yield aryl radicals, the mechanisms of these reactions are of current interest, and both the thermolytic and the photolytic behaviour 3-alkyl-l,3-diaryltriazenes have been studied in some detail (M.Julliard, G.Vernin and J.Metzger, Helv. Chim. Acta, 1980, 63, 467). In related work the thermal decomposition of 1,3-diphenyltriazene in the presence of methylpyridines has been a analysed (G.Vermin, A.K.Shafei and J.Metzger, J. Chem. Res. Synop., 1980, 150). If 1-aryl-3,3-diethyltriazenes are decomposed in the presence of a cation exchange resin [H+-AG 50W-X12(Bio-Rad)] and H21SO phenols labelled at the oxygen atom are produced (N.Sityamurthy et al., Tetrahedron Letters, 1990, 31, 4409). 1-(4-Methylphenyl)-3-methyltriazene reacts with alkyl halides under phase transfer conditions (e.g. in the presence of BunPI) to afford 3-alkylated derivatives. 1,3-Diphenyltriazene also reacts in this way, but on N-acylation with benzoyl chloride the product is benzanilide (Y.Hashida et al., Nippon Kagaku Kaishi., 1989, 1119). 1-Aryl-3-alkyltriazenes (7) react with N-chloro-N-phenylmethylsulphonamide (MeSO2NPhC1) to give anilines and azobenzenes, probably via aryl nitrenes (8) which act as reaction intermediates (O.O.Orazi, Tetrahedron Letters, 1982, 23, 293). Ar ,, N~ N,,N., R

MeSO2N(Ph)CI~ Ar., N" N~'N .. R

i

(7)

-RCI

I

H

CI

r. N

(8)

AF

,,NH 2

+

Ar-N=NAr

335 3-Aryl- 1-methyl- 1-(4-methylphenyl)triazenes (9), undergo anodic oxidation to give radical cations, which then fragment into N-(4-methylphenyl)methylamino radicals. The radicals immediately dimerise to afford 5,10-dihydro-2,5,7,10-tetramethyl-5,10-phenazine (10) (B.Speiser and H.Stahl, Tetrahedron Letters, 1992, 33, 4429).

Me

.~~Me -e

ArN~.N "N I Me

_Ar~2+,_,,.

N9I Me

(9) Me i

I :3T Me r

Me

I

Me (10) N-(Arylazo)piperidines (11, R = alkyl, alkoxy, halogeno, nitro etc.) form biaryls (12) when treated with trifluoroacetic acid in aromatic solvents (HArX, X= 3-NO 2, 4-NO 2, 2,5-di-Me, etc.). The first step in these reactions is considered to be the fragmentation of the azo-piperidine bond and the production of an arenediazonium trifluoroacetate salt. This decomposes to an aryl radical which then couples with the solvent (T.B.Patrick, R.P.Willaredt and D.J.DeGonia, J. Org. Chem., 1985, 50, 2232). 2-Aryl-l-(tetrazol-5-yl)triazenes (13) undergo oxidative fragmentation to form arylazoisocyanides (14) when they are stirred in dichloromethane solution containing lead tetraacetate. The cis-isomers are formed first, but these rapidly rearrange to the tram-products (R.N.Butler and D.P.Shelly, Tetrahedron Letters, 1985, 26, 3401).

336 R R

CF3CO2H R- - ~

N202CF3

(11) R

R

-N2

__~ "~

R

HArX ,

i

ArX

,.r

(12)

ArNH-N - N %,,,N,, N I

N -- N

Pb(OAc)4 ..=

N",N " NC

DCM/RT

Ar

Ar.. N~N ~"NC

H

(13)

(14) 15. Hexazenes

A X-ray crystal study of 3,4-diacetyl-l,6-bis(N-4-chlorophenyl)-1,5-hexaazadiene (1) shows that the molecule has two planar halves related by C 2 symmetry. It contains an unusually long N-CO bond (1.403 A) and a short CO bond (1.200 A). In the infra-red spectrum the carbonyl band is exhibited at an unusually high stretching frequency (1755 - 1742 cm-t), suggesting that the acetyl groups in the molecule have strong electrophilic character. Acylation can be effected using alkoxides (D.Mackay, D.D.Mclntyre and N.J.Taylor, J. Org. Chem., 1982, 47, 532).

COMe I

Ar ~'N~Ns N" N" N~N ~,Ar !

COMe (1)

337 Formylsilanes and most of their derivatives are unstable compounds, however, 2,4-nitrophenylhydrazones have been prepared and these particular compounds are stable in air and in contact with water (R.B.Silverman, X.L.Lu and G.M.Bank, J. Org. Chem., 1992, 57, 6617).

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339

Guide to the Index This index is constructed in a similar manner to the volume indexes of the first edition of the Chemistry of Carbon Compounds. However, to make the index easier to use, more descriptive entries have been made for the commonly occurring individual, and groups of chemicals. The indexes cover primarily the chemical compounds mentioned in the text, and also include reactions and techniques, where named, and some sources of chemical compounds such as plant and animal species, oils, etc. Chemical compounds have been indexed alphabetically under the names used by authors, editing being restricted to ensuring uniformity of entries under the same heading. In view of the alternative nomenclature that can often be used, a limited amount of cross-referencing has been done where it is considered to be helpful, but attention is particularly drawn to Convention 2 below. For this and the succeeding volumes, the indexing conventions listed below have been adopted. 1. A l p h a b e t i s a t i o n

(a) A letter by letter alphabetical sequence is followed for entries, firstly for the main entry, followed by the descriptive entry. (b) The following prefixes have not been counted for alphabetising: n-

ompvic-

assymgemlin-

mesocistrans-

CONSBz-

EZ-

PySome prefixes and numbering have been omitted in the index, where they do not usefully contribute to the reference. (c) The following prefixes have been alphabetised: Allo Epi Neo Anti Hetero Nor Bis Homo Pseudo Cyclo Iso 2. Cross references

In view of the many alternative trivial and systematic names for chemi-

340 cal compounds, the indexes should be searched under any alternative names which may be indicated in the main body of the text. Only a limited amount of cross-referencing has been carried out, where it is considered that it would be helpful to the user.

3. Derivatives Simple derivatives are not normally indexed if they follow in the same short section of the text. 4. Collective and plural entries In place of "- derivatives" the plural entry has normally been used. Plural entries have occasionally been used where compounds of the same name but differing numbering appear in the same section of the text. 5. Main entries The main entry of the more common individual compounds is indicated by heavy type. Multiple entries, such as headings and sub-headings over several pages are shown by "-', e.g., 67-74, 137-139, etc.

341

Index Acetaminophen (paracetamol), 86 -, bio oxidation, 47 Acetone arylhydrazones, reaction with acetyl isocyanate, 295, 296 Acetone 4-chlorophenylhydrazone, reaction with bromine/acetamide, 219 Acetone phenylhydrazone, reaction with phenylisocyanate, 295 Acetophenone, selective reduction to semidione radicals, 311, 312 (~6-Acetophenone)chromiumtricarbonyl complexes, deprotonationhydroxyalkylation, 210 ~-Acetoxyallylarylhydrazones, 263, 264 2-Acetoxy-1-azacyclohepta- 1, 4, 6-triene, 319, 320 N-Acetoxy-1, 4-benzoquinonimine, 70 3-Acetyl-4-acyl-l-(nitrophenyl)pyrazoles, synthesis from 1,3dicarbonyl compounds, 303 3-Acetyl-5-amino-4-ethoxycarbonyl-l-(2nitrophenyl)pyrazole, 303 5-Acetyl-4'-amino-2-hydroxy-3', 5'dimethylbiphenyl, 266 3-Acetyl-l-aryl-5-chloro-4, 5-dihydro-4methylpyridazin-(5(1H)-ones, 288 4-Acetyl-l-aryl-5, 5-dimethyl-1, 2, 4triazolidin-3-ones, 296 3-Acetyl-l-aryl-6-methyl-lH-pyridazin4-ones, 287 3-Acetyl-5-aryl- 1-(thiazol-2yl)formazans, synthesis from pyruvaldehyde/2-thiazolediazonium sulphate, 313, 314 2-Acetylbenzenediazonium chloride, reactions with anilines, 328 - , - with alkylamines, 299 Acetyl-1, 4-benzoquinone, additions of silyl vinyl ethers, 13 2-Acetyl-1, 4-benzoquinone, 9 N-Acetyl- 1, 4-benzoquinone imine, 47 N-Acetyl- 1, 4-benzoquinone monoimines, acid hydrolysis, 47

N-Acetyl-1, 4-benzoquinonimine Noxide, rearrangement to N-acetoxy1, 4-benzoquinonimine, 70 2-Acetylbenzyl 3-butenyl ether, photocyclisation, 41 3-Acetyl-3, 4-dihydro-4hydroxycinnoline, synthesis from ethyl 2-(N-phenylhydrazono)but-3onoate, 290 N-(4-Acetyl-2, 5-dimethylphenyl)-4amino-3, 5-dimethylaniline, 266 4-Acetyl-2, 6-dimethylphenyl 4-amino3, 5-dimethylphenyl ether, 266 N-Acetylhydrodopaquinone, 31 2-Acetyl-5-imino-4-phenyl-A2-1, 3, 4thiadiazoline, 286 2-Acetylindoles, synthesis from benzenediazonium salts/ethyl acetoacetates, 250, 251 3-Acetyl-1-(4-methylphenyl)triazene, 328 3-(2-Acetylphenyl)-l-alkyltriazenes, tautomerism, 299 1-[(N-Acetyl-N-phenyl)amino]-2, 2di(methoxycarbonyl)aziridine, 292 1-[(N-Acetyl-N-phenyl)amino]-5, 5di(methoxycarbonyl)l, 2, 3-triazol2-ine, 292 4-Acetylphenyl 4-amino-3, 5dimethylphenyl ether, 266 4-Acetylphenyl 4-amino-3, 5dimethylphenyl sulphide, 266 1-Acetyl-2-phenylhydrazine, 257 N-Acetylphenylhydrazones, reaction with diazomethane, 292 Acridines, synthesis from N-chloro-1, 4benzoquinone monoimines, 47 3-Acyl-3-alkyl-l-aryltriazenes, basecatalysed deacylation to 3-alkyl-1aryltriazenes, 327 N-Acylanilines, methylation, 80 4-Acyl-2-aryl-5-(arylsulphonyl)-

342 pyrazoles, synthesis from 1,3dicarbonyl compounds, 304 2-Acyl-1, 4-benzoquinone, additions of phenols, 13 Acyl-1, 4-benzoquinones, 17 4-Acyl-5-ethoxy-3-imino- 1phenylpyrazolidines, 283 Acylhydroquinones, synthesis from aldehydes/l, 4-benzoquinones, 23 N-Acylindoles, synthesis from arylhydroxamic acids/vinyl acetate, 68 Acylpentanitrobenzenes, side chain nitration, 59 1-(2-Acylphenyl)-2-aryldiazenes, 229 5-Acyl-4-phenyl-1, 2, 3-triazoles, 321 Alcohols, photoregeneration, 38 Alkanal arylhydrazones, pyrolysis, 278, 279 Alkanones, c~-arylation, 239, 240 Alkenes, arylation, 216 - , - by arenediazonium tetrafluoroborates, 239-241 2-Alkenyl- 1-aryldiazenes (arylazoalkenes), 219 Alkenylcyclobutenolones, ring expansions, 1 2-Alkenyl-l-phenyldiazenes, synthesis from alkanal phenylhydrazones, 219 a-Alkoxybenzyl phenyl ketone phenylhydrazones, 219, 220 5-Alkoxycarbonyl- 1-arylamino- 1Htetrazoles, synthesis from hydrazonyl chlorides, 310 2-Alkoxychromans, synthesis from benzoquinone methides, 38 4-Alkoxy-2-nitrobenzaldehyde phenylhydrazones, selective reduction, 264 4'-Alkylacetanilides, electrolysis, 53 N-Alkylamide hydrazones (amidrazones), 295 Alkylanilines, synthesis from nitrosoarenes, 61 N-Alkylanilines, chromiumtricarbonyl complexes, reactions with nucleophiles, 83 -, nuclear acylation, 83 (~6-Alkylarene)chromiumtricarbonyl

complexes, benzylic hydroxymethylation, 205 -, deprotonation-electrophile quenching, 204-206 -, nitrosation, 204 Alkyl N-arylcarbamates, methenation, 90 2-Alkyl-1-aryldiazenes (arylazoalkanes), 219 -, synthesis from arenediazonium salts, 219 ~-Alkyl-N-arylnitrones, synthesis from nitrosoarenes/alkylamines, 69 3-Alkyl-1, 3-diaryltriazenes, fragmentation into aryl radicals, 333 Alkyl diphenylmetallophanes, thermal degradation, 90 Alkyl esters, c~-amination, 240 3-Alkyl-3-formyl- 1-aryltriazenes, potential metabolites of 3, 3-dialkyl-1aryltriazenes, 327 5-Alkylfuran-2(5H)-ones, reactions with phenylhydrazines, 269 3-Alkyl-4-hydroxymethyl-3, 4dihydrobenzotriazines, tautomerism, 299 2-(Alkylidene)diazocyclohexadienes, synthesis from arylazo sulphides, 217 3-Alkyl-4-methylene-3H-benzotriazines, 299 2-Alkylphenols, nitration, 56 Alkyl N-phenylcarbamates, as radical initiators, 90 2-Alkyl-1-phenyldiazenes, synthesis from alkylamines/nitrosobenzene, 219 Alkynylaminocarbene chromium complexes, 189 Allophanates, kinetics of formation, 90 (776-Allylarene)chromiumtricarbonyl complexes, benzylic alkylation, 206 N-Allyl-N-arylhydroxylamines, synthesis from nitroarenes, 67 Ambazone, reduction by ascorbic acid, 261 Amidrazones (N-alkylamide hydrazones), 295 Aminating agents, 73, 74 2-Amino-5-(4-aminoaryl)tropolones, hydrolysis to 5-aryltropolones, 313

343 6-Amino- 1-aryl-5-cyano-3ethoxycarbonyl-1, 4-dihydro 4methylpyrazines, 252 5-Amino-1-aryl-3-cyanopyrazoles, 274 5-Amino-4-(2-aryldiazene-l-yl)-3hydroxypyrazoles, 279, 280 6-Amino-5-( 1-aryldiazen-2-yl)- 1, 3dimethyluracils, reactions with ethyl propiolate, 222 4-Amino-4-(N-arylhydrazono)3-(pyridin-l-yl)-l, 2, 5, 6tetrahydropyridin-2, 6-dione chlorides, synthesis from chloroimides, 291 5-Amino- 1-aryl-3-methyl-4thioformamidopyrazoles, 274 4-Aminobenzaldehydes, synthesis from 4-azidobenzaldehydes, 321 4-Aminobenzophenone, synthesis from benzanilide, 86 2-Aminobenzophenones, methods of preparation, 74 1-(a-Aminobenzylidene)-lphenyltriazenes, 332 Aminobiphenyls, methods of synthesis, 68 Amino Claisen rearrangements, 84 6-Amino-2, 3-dihydro-2-phenyl-1, 2, 4benzotriazin-3-one, 253 3-Amino-4-( 2-hydroxybenzoyl)- 1phenylpyrazole, 275 11-Aminoisoquinolino [4,3-b]indazole, synthesis from 2,2'dicyanoazobenzene, 229, 230 2-Amino-4-methyl-5-(phenylazo)thiazole, 286 5-Amino-3-methylthio- 1-phenyl1, 2, 4-triazole, synthesis from phenylhydrazine/guanidines, 295 2-Amino-4-nitrobenzoic acids, synthesis from 2-nitrobenzylidene malonates, 63 2-Amino-2-(2-phenylhydrazinyl)propanedioic acid, 311 6-(2-Aminophenyl)-2, 3, 4, 5tetrahydro-1, 2, 4-triazine-3, 5-dione, diazotisation and coupling with ethylcyanoacetyl carbamate, 298 Aminoterephthalate, diazotisation, 53

Aminotetranitrotoluenes, 58 4-Amino-I, 2, 4-triazole, aminating agent, 73 Angiotensin K-13, 177, 178 Anilides, industrial importance, 85 -, photobromination, 85 -, polymerisation, 85 -, synthesis from aroylazides, 84 , from oximes, 84 - , - from tosylhydrazones, 84 Aniline, diazotisation in polyethylene glycol, 246 -, irradiation with ultraviolet light, 225 -, manufacture, 74 -, synthesis from nitrobenzene, 63 Anilines, N-alkylation, 78, 82 -, aminoethylation, 82 -, deamination, 75, 76 -, formylation, 80 -, halogenation, 75 -, methods of preparation, 70-73 -, N-methylation, 78 -, nitration, 56-58 -, 13NMR spectra, 74 -, nuclear alkenylation, 83 -, nuclear alkylation, 83 -, one-electron oxidation, 83 -, oxidation, 74 -, N-phenylation, 82 -, reductive acylation, 80 -, synthesis from aroyl chlorides, 73 , from arylazides, 72 , from benzamides, 73, 74 , from cyclohexenone oximes, 74 , from formamidines, 80 , from phenols, 72 , from thioamides, 80 - - f r o m thioimidates, 80 Aniline-stabases, 74 Anils, synthesis from arylamines/ ethylmagnesium bromide, 76 Anisolemanganesetricarbonyl complexes, reactions with nucleophiles, 159, 160 Anthacyclins, 35, 36 Anthracene, lithiation, 98 -, reaction with antimony trichloride, 145 Anthranilate esters, synthesis

344 from vinylketenimines/acetylenecarboxylates, 81 9,10-Anthraquinone methides, synthesis from methylenecyclobutenols, 40, 41 Araldehyde 2-aminophenylhydrazones, oxidation to 1, 2, 4-benzotriazines, 300 (~6-Araldehyde)chromiumtricarbonyl complexes, 189 -, reactions with enolates, 209, 210 Araldehydes, synthesis from arenediazonium tetrafluoroborates, 240 Areneazo cyanides, aryldiazene carbonitriles, 216 Arenecarboxylic acids, synthesis from benzenediazonium salts, 249 (776 -Are n e )chro mi um tri carbon yl complexes, arene deprotonationelectrophile quenching, 202, 203 -, as hydrogenation/isomerisation catalysts, 211 -, chemistry, 185-211 -, electrophilic substitutions, 193, 194 -, general chemistry, 193-211 -, lithiation, 201, 202 -, nucleophile addition--electrophile addition, 200-202 -, nucleophile addition-oxidation, 197-202 -, nucleophilic additions, 194-202 -, pericyclic reactions, 207-209 -, photochemical generation, 187 -, structures, 192, 193 (Arene)cobaltcyclopentadienyl complexes, 213 ~l-Arene complexes, 163 ~?2-Arene complexes, 162, 163, 183 Arenediazonium chlorides, 238 -, reactions with 1, 3-diaminobenzene, 225 -, - with 5-phenylamino-2-pyrazolin-3one, 280 -, use in chloroarylation, 240, 241 Arenediazonium ions, complexation by multidentate ligands, 238 Arenediazonium methanesulphonates, 236

Arenediazoniums, dediazotisation, 75, 76 -, synthetic applications, 75, 76 Arenediazonium salts, coupling with active methylene compounds, 238 -, reactions, 238 , with carboxylate anions, 238 -, - with 2-oximinopropane, 331 , with quaternary salts, 238 -, reduction, 243 -, synthetic methods, 236 Arenediazonium tetrafluoroborates, as arylating agents, 238, 239 -, reactions with alkali metal thiocarboxylates, 248 with carbonitriles/sodium carboxylates, 243 with the dianion of 1,2dinitrobenzene, 227 with the dianion of 1, 4dinitrocyclooctatetrene, 227 Arenedi(rheniumcyclopentadienyldicarbonyls), 163 (Arene)iridiumcyclopentadienyl complexes, 212, 213 (Arene)ironcyclopentadienyl cations, reactions with nucleophiles, 172-175 -, stability, 171, 172 (~6-Arene)ironcylopentadienyl cations, 165 (Arene)manganese complexes, 152-157 (Arene)manganesedicarbonyl halides, halide displacement, 157, 158, 160 (Arene)manganesetricarbonyl complexes, reactions with nucleophiles, 153-162 (Arene)manganesetricarbonyl tetrahydrofuran complexes, 154, 155 6 (7/-Arene)molybdenumtricarbonyl complexes, 211, 212 (~2 -Arene)osmium(II) complexes, 183185 (Arene)rheniumtricarbonyl complexes, 156 (~1 -Arene)rhodium complexes, 214 (~2-Arene)rhodium complexes, 214 (Arene)rhodiumcyclopentadienyl complexes, 213

345 (Arene)rutheniumcyclopentadienyl complexes, 213 (~6-Arene)rutheniumcyclopentadienyl cations, 165 Arenes, activation by transition metal complexation, 151, 152 -, asymmetric complexation, 189-192 -, direct amination, 68 -, lithium derivatives, 95-109 -, nitration, 55 , by 4-methyl-4-nitro 2, 3, 5, 6tetrabromocyclohexa-2, 5-dienone, 58 -, synthesis from arenediazonium tetrafluoroborates, 243, 245 -, thallation, 127, 128 -, vicarious nucleophilic substitution, 62, 63 (~6.Arene)tungstentricarbonyl complexes, 211, 212 Aromatic nitrosation, 64 Aroylazides, rearrangement to anilides, 84 Aroyl-1, 4-benzoquinones, 17 N-Aroylimines, reactions as heterodienes, 46 2-Aroyl-l-(4-nitrophenyl)hydrazines, arylation, 257 ~-Aroyl-N-phenylnitrones, synthesis from nitrosobenzene]silylenol ethers, 70 Arsabenzene, electrophilic substitution, 145 Aryl-copper-zinc complexes, 118 Aryl-iron-lithium hydrides, 102 Aryl-metal-lithium clusters, 100-103 4'-Arylacetanilides, electrolysis, 53 (N-Aryl)acetohydrazonoyl halides, synthesis, 301 Arylalkoxy tetrasulphides, 258 1-Aryl-3-alkyltriazenes, reactions with N-chloro-Nphenylmethylsulphonamide, 333 Arylalkynes, cyclisations, 119 Arylaluminiums, 126 Arylamides, reduction, 73 N-(Aryl)amides, methods of preparation, 84 N-Arylamides, ortho-metallation, 86

Arylamines, as arylating agents, 260 -, formation in the attempted Fischer indolisation of arylhydrazones, 270 -, oxidation, 59, 60, 85 - , - by chromyl chloride, 224 -, N-substituted, 78 -, synthesis from arylazides, 321 5-Arylamino-2-(2-aryldiazene- 1-yl)- 1, 4dihydroxybenzenes, 268 2-(Arylamino)benzo [c, d] indazol-3(2H)ones, 324, 325 N-(Arylamino)guanidinium chlorides, synthesis from arylhydrazinium chlorides/N, N-dimethylaminonitrile, 260 1-Arylamino-2-methyl-4, 6diphenylpyridinium salts, photolysis, 68 (N-Arylamino)methyl phenyl ketones, Aza-Wittig reactions, 285 8-(N-Arylaminomethyl)theophyllines, synthesis from 6-amino-5-(1aryldiazen-2-yl)-l, 3-dimethyluracils, 222 Arylarsenicals, 145, 146 Aryl 2-(arylazo)-2-(phenyl)ethyl sulphones, 218 Aryl arylazoxy sulphones, use as arylating agents, 218 1-Aryl-3-[(aryloxy)methyl]-3methyltriazenes, synthesis from 3-acetoxymethyl- 1-aryl-3methyltriazenes/phenols, 331

N-Aryl-C-( arylsulphon yl )formohydrazonoyl bromides, 304 Arylazides, addition reactions with 1-acyl-2-phenylethynes, 321 -, photochemistry, 319, 320 -, photolysis, 68 -, reactions, 319-327 , with phosphaalkenes, 323 with phenylisocyanate, 322, 323 , with potassium cyanide/dimethylsulphate, 328 -, reduction to anilines, 72, 326 -, thermolysis to arylamines, 326 -, uses in heterocyclic syntheses, 321-327

346 Arylazoalkanes (2-alkyl- 1-aryldiazenes ), 219 -, synthesis from arenediazonium salts, 219 Arylazoalkenes (2-alkenyl-1aryldiazenes), 219 Aryl azoaryl sulphones, reactions with norbornene, 218, 219 1-(Arylazo)-8-azido-2-hydroxynaphthalenes, 324 Arylazo 'butyl sulphides, arylating agents for enolates and phenols, 217 1-Arylazo-2, 2-dichloroethenes, reactions with amines, 221, 222 1- [(Arylazo)diphenylmethyl] pyridinium bromides, 264 Arylazo exchange, 247 1-Arylazo-4-nitrooctatetraenes, synthesis from arenediazonium tetrafluoroborates, 227 Arylazoperoxides, 263 Arylazophenols, reactions with 4nitrobenzenediazonium tetrafluoroborates, 247 N-(Arylazo)piperidines, fragmentation into biaryls, 334 Arylazo sulphides, decomposition to arylfluorides, 217 -, synthesis from arenediazonium chlorides and N-acetylcysteine, 216, 217 Arylazo sulphides and oxidised derivatives, 216 4-Arylazo-1, 2, 3-trimethylpyrazoles, synthesis from 2, 3, 4-pentanetrione, 277, 278 4-Arylazo- 1, 3, 5-trimethyl- 1-pyrazoles, synthesis from 2, 3, 4-pentanetrione hydrazones, 277, 278 N-Arylbenzohydrazonoyl bromides, reactions with 3hydroxypropynecopper(I), 305 - , - with phenylethynecopper(I), 305 2-Aryl-2H-benzotriazole-l-oxides, 85 1-Aryl-3-benzyl-5-(4, 6diphenylpynmidin-2-yl)formazans, complexes with divalent metal ions, 318 Arylberylliums, 112

Aryl 1, 4-bis(diazo carbonitriles), charge-transfer complexes with tetrathiofulvalenes, 216 -, synthesis from 1, 4-aminoarenes, 216 , from 1, 4-bis(N-nitrosoacetylamino)arenes, 216 Arylbismuth complexes, preparation and reactions, 148 Arylborinic acids, 142, 143 Arylboron compounds, 123-125 Arylboronic acids, 142-144 1-Aryl-2-bromodiazene 1-oxides, synthesis from nitroso bromides 1-aryl-2-bromodiazene 1-oxides, 216 1-Aryl-2-(2-bromoethyl)diazene 2oxides, 223 Arylcadmiums, 117, 118 Arylcaesiums, 109, 111, 112 Arylcalciums, 112, 116 N-Arylcarbamates, alkylation, 90 -, methods of preparation, 89, 90 -, physical properties, 90 -, reduction, 90 1-Aryl-3-[2-(2-chloroethylthio)ethyl]triazenes, cytotoxic properties, 326, 327 N-Aryl-C-(chloroformyl)formohydrazonoyl chlorides, as sources of nitrilimines, 303, 304 -, reactions with amines/enamines/ imines, 305 2-Arylcinnolines, synthesis from 2(arylazo)phenylacetic acids, 231 Arylcyclotriphosphazines, 114, 115 Aryldiazene carbonitriles, areneazocyanides, 216 Aryldiazene oxides, 223 3-(Aryldiazenyl)pentane-2, 4-diones, reactions with acylhydrazines, 251 1-Aryldiazen-2-yl thioesters, fragmentation into aryl radicals, 248 1-Aryl-3, 3-diethyltriazenes, decomposition into phenols, 333 2-Aryl-2, 3-dihydro-4-quinolones, 46 2-Aryl-4, 4-dimethyl-5-phenylpyrazol3-ones, synthesis from ethyl 2,2dimethyl-3-phenylpropan-3-onoate, 280

347 1-Aryl-4, 5-diphenylpyrazolin-3(2H)ones, 280, 281 Aryl ethers, synthesis from arenemanganesetricarbonyl halides, 160-162 , from arenerutheniumcyclopentadienyls, 177 -, - from dinitroarenes/alkoxides, 62 2-Aryl-5-ethoxycarbonyl-4(arylhydrazono)pyrazol-3(4H)-ones, 308 2-Aryl-6-e tho xycarbo nyl-4-cyan 0-5methylpyridazin-3-(1H)-ones, 287 N-Aryl-C-( e th oxycarbo n yl )formohydrazonoyl chlorides, reactions with sodium ethoxide, 308 Aryl ethoxy tetrasulphides, decomposition to di(aryl) tetrasulphides and diethoxy tetrasulphide, 258 Aryl fluorides, synthesis from arylazo sulphides, 217 - , - from arylgermaniums, 136 1-Aryl-3-formyltriazenes, 245 Arylgermanes, 128 Aryl germanium catenates, photolysis, 138 Arylgermaniums, reactions with fluorine, 136 -, spectra, 130 Aryl Grignards, amination, 72 Aryl halides, cathodic reduction, 118 Aryl(heteroaryl)formazans, synthesis from heteroarylformylhydrazones/ arenediazonium chlorides, 317 1-Aryl-3-heteroarylpropenones, 282 Arylhexazenes, 335, 336 Arylhydrazine, conjugate additions to enones, 268, 269 Arylhydrazines, acylation, 257 -, alkylation, 257 -, as arylating agents, 258, 260 -, as reductants, 257 -, reactions with 2, 5-bis(arylamino)-3carboxy-1, 4-benzoquinones, 268 , with 2-cyano-3-ethoxyacrylonitrile, 274, 275 , with 2-cyano-3-ethoxybut-2enethiamide, 274 , with dialkoxy disulphides, 258

-, synthesis from N(diphenylphosphonoyl)arylamines, 256 -, reaction with methyl 2,2,2trifluoroethyliminoether, 294 -, synthesis from arylhydrazones, 256 , from aryllithiums, 256 , from arylmagnesium bromides, 256 -, synthetic methods, 256, 257 -, use in the synthesis of diazenes, 260 in the synthesis of heterocycles, 256 2-(2-Arylhydrazinyl)tropolones, benzidine-type rearrangements, 313 Arylhydrazones, 256 -, hydrolysis, 262 -, oxidative coupling, 263 -, physical properties, 260 -, reactions, 262-301 -, reactions as nucleophiles, 267 -, rearrangement reactions, 264 -, reduction, 264 -, synthesis, 261, 262 -, uses in heterocyclic synthesis, 269301 2-(Arylhydrazono)cyclohexanones, synthesis from arenediazonium salts/ 1-trimethylsilyloxycyclohexene, 261 3-(N-Arylhydrazono)pentan-2, 4-diones, acetylation, 287 4-Arylhydrazono-5-(phenylamino)pyrazolin-3-ones, 280 N-Arylhydrazonoyl halides, 301-310 Arylhydroxamic acids, reactions with vinyl acetate, 68 N-Arylhydroxamic acids, synthesis from nitrosoarenes/glyoxylic acid, 65 1-Aryl-3- [(hydroxyaryl )methyl]3-methyltriazenes, synthesis from 3-acetoxymethyl- 1-aryl-3methyltriazenes/phenolates, 331 Arylhydroxylamines, Bamberger rearrangement, 68 -, oxidation, 64 -, oxidation-reduction, 67 -, pre-equilibration with nitrosoarenes, 67 N-Arylhydroxylamines, synthesis from nitroarenes, 66 -

348 Arylhydroxylamine-O-sulfates, 75 1-Aryl-5-hydroxymethyl-3phenylpyrazoles, 305 1-Aryl-3-hydroxy-5-ipropyl-1, 2, 4triazoles, 297 (~6-2-Arylidene- 1-tetralone)chromi umtricarbonyl complexes, reactions with nitromethane anion, 211 Aryliminodimagnesiums, 76 2-Arylindazoles, synthesis from azoarenes, 231, 232 Aryliridium(III) complexes, 121, 122 Arylisocyanates, methods of preparation, 87 -, physical properties, 87 -, reactions with nitrite anion, 88 -, synthesis from 3,3-dialkyl-1arylureas, 215 -, trimerisation, 87 N-Arylisocyanates, synthesis from N-arylcarbamates, 90 Arylisocyanides, methods of synthesis, 91 Arylisothiocyanates, synthesis from methyl N-aryldithiocarbamates, 91 Aryl ketones, synthesis from arenediazonium, tetrafluoroborates/ CO/palladium(II) acetate, 248, 249 - from benzenediazonium salts, 249 Arylleads, 139-143 -, spectra, 130 Aryllithiums, 95-109 -, amination, 72 Aryl mercuration, 119 Arylmercurials, 117-119 Arylmercuric chlorides, methods of synthesis, 119, 120 -, reactions, 121 3-Aryl- 1-methyl- 1-(4-methylphenyl)triazenes, anodic oxidation, 334 5-Aryl- 1-(2-methyltetrazol-5-yl)-3phenylformazans, synthesis from benzaldehyde, 314 2-Aryl-5-methyl- 1, 2, 4-triazolin-3(4H)ones, 297 Arylnitrile imides, arylnitrilimines, 301-310 Arylnitrilimines, arylnitrile imides, 301-310 -

-, as reactive intermediates in heterocyclic synthesis, 303-310 Aryl nitronates, oxidation, 61 N-Arylnitrones, methods of preparation, 69 -, synthesis from phenylhydroxylamines, 69 Arylnitrosamines, synthesis, 215 N-Aryl-N-nitrosoacetamides, synthesis from N-arylacetamides, 216 Aryl-N-nitrosoamines, reactions with acids, 216 N-Arylnitroxides, methods of preparation, 69 5-Aryl-1, 2, 3, 3a, 4, 5, 6, 6a-octahydro1, 3-diphenylpyrrolo[3, 4-c]pyrazole4, 6-diones, 282 N-Aryloxazolidinones, synthesis from arylcarbamates, 90 Aryloxychlorides, 246 Aryloxyhydroquinone dimethyl ethers, 51 3-Arylpentanediones, synthesis from arylazo sulphides, 217 N-Arylphosphazenes, 92, 93 1-Aryl(piperid-l-yl)triazenes, as a source of diazonium salts, 236 Arylpotassiums, 109-112 2-Aryl-5-ipropyl - 1, 2, 4-triazolin-3(1H)ones, 297 Arylselenides, 149 Arylsilanes, 128 -, spectra, 130 Arylsilvers, 128 Arylsilyl complexes, charge distribution, 132 Arylsodiums, 109-112 Arylstannanes, 140 N-Arylsulphamides, 92 N-Arylsulphenamides, 92 Arylsulphonyl- 1, 4-benzoquinones, 17 Aryltellurides, 149, 150 2-Aryl-2, 3, 5, 6-tetrahydro-3, 6diphenylpyranopyridazin-8-ones, synthesis from pentane-2, 3, 4-triones 2-(arylhydrazones), 287, 288 1-Aryl-3-(tetrazol-5-yl)triazenes, as a source of arenediazonium salts and 5-aminotetrazole, 236

349 2-Aryl-l-(tetrazol-5-yl)triazenes, oxidative fragmentation into arylazoisocyanides, 334, 335 3-Aryl-l-tetrazol-5-yltriazenes, bench stable diazonium equivalents, 76 Arylthalliums, 127, 128 Arylthioesters, synthesis from benzenediazonium salts, 248 Aryltin halides, 140 Aryltins, 139-143 -, spectra, 130 Aryltrialkylgermanes, 138, 139 Aryltriazene N-oxides, charge transfer complexes, 333 -, reactions with picric acid, 333 -, synthesis from nitroso compounds, 331 Aryltriazenes, 216 -, acylation, 328 -, biological importance, 326, 327 -, cyclisation to 3-hydroxybenzotriazines, 328 -, diazoamino derivatives, 326 -, fragmentation into aryl radicals, 333 -, reactions, 332-334 -, synthesis from arenediazonium salts/ amine, 328 - , - from arenediazonium tetrafluoroborates/formaldehyde, methylamine, 330 Aryltriazines, synthesis from glyoxal arylhydrazones, 330 Aryltriazenes, synthesis from 2oximinopropane]arenediazonium salts, 331 - - f r o m 1, 3-thiazolidines, 327 Aryltributylstannanes, 140 Aryltriflates, synthesis from arenediazonium tetrafluoroborates, 246, 247 Aryltrifluorosilyl-18-crown-6 potassium complexes, 132, 134 1-Aryl-3, 4, 5-trimethylpyrazoles, 278 5-Aryltropolones, 313 Arylureas, 216 N-Arylureas, methods of preparation, 90 Arylzincs, 117

Asymmetrical azoarenes, synthesis from acetanilides/nitrobenzenes, 219 Aza-Wittig reactions, 285 Azepines, 226 Azepin-2(1H)-ones, synthesis from arylazides, 319, 320 Azepin-2(3H)-ones, 319, 320 Azides, as aminating agents, 72 2-Azidobenzaldehyde, reaction with triphenylphosphine, 321, 322 4-Azidobenzaldehydes, reduction to 4-aminobenzaldehydes, 321 2-Azidobenzonitrile, photoinduced ring expansion, 319, 320 3-Azido-1, 2-benzoquinone, thermolysis, 27, 28 N-(2-Azidobenzoyl)phenylhydrazine, 325 2-Azidobiphenyl, reaction with aluminium trichloride, 323 (2-Azidophenyl)phenylmethane, reaction with aluminium trichloride, 323 1-Azido-2-(phenylthio)-9, 10anthraquinone, synthesis from 1-amino-2-(phenylthio)-9,10anthraquinone, 324 Aziridines, reactions with chloranil, 23, 24 Aziridino-1, 4-benzoquinones, 4 Azoanthranils, 325 Azoarenes, 1, 2-diaryldiazenes, 224 -, reactions with carbenes, 231 -, reduction to hydrazobenzenes, 229 -, synthesis from nitrobenzenes, 232 , from nitrosoarenes, 76 -, synthetic methods, 224-229 Azobenzene, reduction by dihydrolipoamide/Fe 2§, 234 -, reaction dichlorocarbene, 231, 232 -, synthesis from aniline, 225 - , - from hydrazobenzene, 225, 312, 313 Azobenzene-~-hydroperoxide, source of benzenediazonium cation, 236 Azobenzenes, 47 - , c i s - t r a n s isomerism, 232 -, synthesis from anilines, 224, 225 - , - from arenediazonium chlorides, 225 , from nitrosobenzenes, 66

350 Azobenzenes (cont'd) -, synthetic methods, 224-229 [2.2](4, 4')Azobenzenophane, synthesis from 4, 4'-dinitrobibenzyl, 228 Azo coupling, 249 Azoxyarenes, 1, 2-diaryldiazene oxides, 232 -, synthesis from arylamines, 232 from nitroarenes, 76, 232 Azoxybenzene, reduction by dihydrolipoamide/Fe2§ 234 Azoxybenzenes, ortho-Wallach rearrangements, 235 Bamberger rearrangement, 68 Beckman rearrangement, 84 Benzaldehyde hydrazone, reaction with methyl 2-chloro-2-(phenylhydrazono)acetate, 308 Benzaldehyde phenylhydrazone, cycloadditions with arylmaleimides, 282 (E)-Benzaldehyde phenylhydrazone, crystal structure, 260 Benzanilide, Fries rearrangement, 86 Benzazirine, 319, 320 Benzene, dilithiation, 96, 97 -, mononitration, 57 -, nitrosoation, 64 Benzene-aluminium complexes, 126 Benzene-gallium complexes, 126, 127 Benzenediazonium chlorides, reactions with peracids, 246 Benzenediazonium salts, reactions with 1, 3-diaminobenzenes, 253 Benzenediazonium sulphate, reaction with sodium diethyl malonate, 227 Benzenemanganesetricarbonyl complexes, 157 Benzenethiols, synthesis from benzenediazonium salts, 247 Benzidine, synthesis from aniline, 74 Benzil, selective reduction to semidione radicals, 311, 312 Benzil bis(phenylhydrazone), isomerism with 1, 3, 4, 6-tetraphenyl-1, 2, 4, 5tetraza-2, 5-hexadiene, 302 Benzil monophenylhydrazone,

photochromic and thermochromic properties, 260 Benzimidazoles, 78 -, synthesis from araldehyde 2aminophenylhydrazones, 300 Benzocyclobutenes, thermolysis, 38, 40 Benzocyclobutenone, radiolysis, 39 Benzocyclooctenediones, 208 1, 2, 3-Benzodiazoauroles, 121 1, 3-Benzodithianes, 107 Benzo-l,3-dithioles, synthesis from benzene-l, 2-dithiol, 222 Benzohydroxamic acids, 66 Benzonitrile, synthesis from aniline, 246 Benzopyranopyridazinones, synthesis from 2-hydroxyaraldehydes, 289 1, 4-Benzoquinolimines, 53 Benzoquinols (hydroxycyclohexadienones), 2, 49, 50 1, 2-Benzoquinols, 52, 53 1, 4-Benzoquinols, 50-52 Benzoquinone, alkylation, 7 -, biodegradation, 29 -, photochemical reaction with benzyl phenyl ether, 23, 24 -, reactions with enamines, 12 1, 4-Benzoquinone, cycloaddition reactions with cyclopentadiene, 15, 16 -, guests in macrocycles, 26, 27 -, oxetane formation with alkenes, 23, 24 -, reaction with 4-nitrophenylazide, 27, 28 1, 4-Benzoquinone N-benzoyl-Nphenylsulphonyldiimines, 48 1, 4-Benzoquinone-cyclopentadiene adduct, 25 1, 2-Benzoquinone dimethides, cycloaddition reactions, 38 -, methods of synthesis, 38-42 1, 4-Benzoquinone imines, 47, 48 1,2-Benzoquinone imines, 46 Benzoquinone methides, 2 -, reactions, 35, 36 1, 2-Benzoquinone methides, equilibration with epoxides, 36, 37

351 1, 4-Benzoquinone methides, methods of synthesis, 42-45 1, 4-Benzoquinone O-oxides, methods of synthesis, 47, 48 Benzoquinones, addition of nucleophiles, 7 -, electron transfer reactions, 1, 3-7 -, heterodienes, 1 -, methods of synthesis, 29-34 -, naturally occurring, 2, 6 -, photochemical reactions, 21-25 -, substitution-elimination reactions, 20, 21 -, synthesis from vinylcyclobutanones, 34 1, 2-Benzoquinones, as heterodienes, 19, 20 -, Diels-Alder reactions, 19 -, nucleophilic addition reactions, 10 1, 4-Benzoquinones, arylation, 5, 6 -, cyclodimerisation, 21, 22 -, Diels-Alder reactions, 14 -, electron transfer from amines, 22 , from metalloporphyrins, 22 -, photochemical reactions with aldehydes, 21, 22 -, photoexcited states, 22 -, photoreduction, 23 -, reactions with chlorine, 13 -, synthesis from cyclobutene-l, 2diones, 32-34 , from 2, 3-dimethylcyclobutenedione/ alkynes, 31, 32 -,from 3-ipropyl-4 methoxycyclobutene-1, 2-dione, 32, 34 Benzoquinonimines, in Gibbs' phenol test, 74, 75 Benzosemiquinones, metal complexation, 31 Benzothiete, reaction with nitrosobenzene, 65 Benzo[b]thietes, sulphur extrusion, 42 Benzo[3, 4-c]thiophene y6-complexes, 187, 188 3, 1-Benzothiosilacyclohexanes, 107 3, 1-Benzothiostannacyclohexanes, 107 Benzotriazines, synthesis from arylhydrazones, 299

-, - from benzenediazonium salts, 253 Benzotriazoles, synthesis from arylhydrazones, 291-299 N-(Benzotriazolylmethyl)arylamines, as anil equivalents, 79 2-(1, 2, 3-Benzotriazol-2-yl)phenols, 230 Benzoxaborins, thermolysis, 36, 37 1, 2, 3-Benzoxadiazoles, intermediates in rearrangement reactions, 236, 237 Benzoxazines, synthesis from arylhydrazones, 290, 291 Benzoylazo compounds, thermolysis, 325 (~e-Benzyl acrylates)chromiumtricarbonyl complexes, Diels-Alder reactions, 208 Benzyl alcohols, synthesis from benzenediazonium salts, 247 (~6-Benzylamine)chromiumtricarbonyl complexes, ortho lithiation, 203 3-(N-Benzylaminocarbonyl)-5-phenyl1, 2, 4, 5-thiatriazole 1-oxide, 287 N-(Benzyl)benzenesulphonamide, reaction with phosphorus trichloride, 297 (776 -Benzyl)chromiumtricarbonyl cations, nucleophile quenching, 206, 207 Benzyl Grignard reagents, 117 Benzylic hydroxymethylation, 205 2-(N-Benzylidenamino)indazole, synthesis via Aza-Wittig reaction, 322 4-Benzylidenamino-5-methoxycarbonyl1-phenyl-1, 2, 4-triazolin-3-one, 308 Benzyllithiums, 117, 129 Benzylmanganesepentacarbonyl, reactions with carbonyl compounds, 163 4-Benzyl-4-methoxy-2, 6dimethylcyclohexadienone, 51 2-Benzyl-4-methoxy-1, 2, 5-thiadiazol-3one 1-oxide, 287 Benzyloxy-1, 4-benzoquinone, reaction with 7-methoxy-2H-chromene, 18, 19 N-Benzyl-N-phenylhydroxylamines, synthesis from anilines, 66 Benzylpotassium, 109 Benzylsilanes, reactions with fluoride ion, 39

352 Benzylzincs, 117 Biaryls, synthesis from arenediazonium tetrafluoroborates, 238, 239 , from N-(arylazo)piperidines, 334 - , - from 4-methyl-2-phenylthiophenol sulphoxide, 46 Biformazans, dehydrogenation, 314 -, reaction with paraformaldehyde/ boron trifluoride diethyletherate, 314 (r/6,r/6-Biphenyl)bis [chromium tricarbonyl] anions, reactions with electrophiles, 205, 206 Biphenyls, synthesis from 4-hydroxyacetophenones, 265, 266 -,from 1-phenyl-2sulphinylhydrazine, 259 Bis(arene)dicyclopentadienyldiiron complexes, 166, 167 Bis(arene)iron(II) complexes, 167, 168 Bis(r/6-arene)iron(II) complexes, 181, 182 Bis(arene)ruthenium(II) complexes, 167, 168 Bis(aryl)cadmiums, 118 Bis(arylcyclotriphosphazines), 114, 115 Bis(aryl)mercurials, 120, 121 -, NMR spectra, 123 3, 5-Bis(aziridino)-l, 4-benzoquinones, 4 2,2-Bis[1-(4-chlorophenyl)diazen-2yl]propane, 219 4, 4'-Bis[2-chloro-2-(pyrid-2-yl)eth- 1yl]biphenyl, 240, 241 4, 4'-Bis(2-cyanoethen- 1-yl)biphenyl, phenylation, 241, 242 4, 4'-Bis [(2-cyano-2-phenyl)eth- 1-yl]biphenyl, 242 2, 2'-Bis(dehydrohydroquinone), electrooxidative desorption, 27, 28 1, 4-Bis(diazonium)benzene ditetrafluoroborate, reactions with disulphides, 248 4, 4'-Bis(diazonium)biphenyl dichloride, reaction with 2-vinylpyridine, 240, 241 N, N-Bis(2-hydroxyethyl)-1, 4phenylenediamine, oxidative coupling, 74 1,1-Bis(2-methoxyphenyl)hydrazine,

synthesis from N,N-bis(2methoxyphenyl)urea, 256, 257 N, N'-Bis(4-methoxyphenyl-2, 2, 2trifluoroethanimidamide, anodic oxidation, 47 Bis(2-methylindolin-3(1H)-on-2-yl), synthesis from 2-hydroxyazobenzenes, 235 1, 2-Bis[(Z)-(2-nitrophenyl)-O,N,Nazoxy]benzenes, 232, 233 1, 2-Bis(phenylamino)-3, 4bis(phenylimino)cyclobutene, synthesis from tetrakis(phenylimino)cyclobutane, 257 4, 4'-Bis [(2-phenyl)ethen- 1-yl]biphenyl, 242 1, 2-B is(2-phenylhydrazin- 1-yl)ethanes, 264 1, 4-B is(2-phenyltetramethyldisilanyl)benzene, photolysis, 132, 133 1, 2-Bis(phenylthio)benzene, synthesis from benzenediazonium salts, 248 4, 4'-Bis [2-(pyrid-2-yl)ethen- 1yl]biphenyl, 240, 241 a, a-Bis(trifluoromethyl)-l, 4benzoquinone, 43 2, 5-Bis(2, 3, 3-trimethylbut-2-yl)aniline, reaction with sodium nitrite/sulphuric acid, 244 2, 5-Bis(2, 3, 3-trimethylbut-2-yl)benzenediazonium hydrogensulphate, thermolysis, 244 2,5-B is(2, 3, 3-trimethylbut-2-yl)phenol, 244 1, 4-Bis(trimethylsilyl)benzene, structure, 130 Bis(trimethylsilyl)chlorophosphaethene, reaction with phenylazide, 323 Bis(verdazylium) ions, reduction, 314 Boyland-Sims, persulfate oxidation, 75 Bromoanilines, diazotisation, 328 4-Bromoanilines, 75 Bromobenzene, synthesis from aniline, 246 N-Bromo-4~ Orton rearrangements, 86 1-Bromo-2-(lithiomethyl)benzene, 107109

353 2-(2-Bromoprop-2-yl)- 1-(4chlorophenyl)diazene, 219 1-Bromo-2-[(trimethylstannyl)methyl]benzene, 107, 108 (~6-Butenoylarene)chromiumtricarbonyl complexes, conjugate additions, 210 N-(' Butoxycarbonyl)aniline, metallation, 86 3-tButy1-1, 2-benzoquinone, nucleophilic addition reactions, 11 4-tButyl-1, 2-benzoquinone, reactions with enamines, 19, 20 2-'Butyl-4, 6-dinitrophenol, synthesis from 2-'butyl-4, 6-dinitrocyclohexa2, 4-dienone, 57 NJ Butyl-N-methylformamididine, reactions with electrophiles, 80 Caged compounds, 61 Calix[6]arene, mono oxidation, 47 Calixarenes, 37 Calix[4]arenes, tetrasubstituted, 249 Calix[1, 6]-para-quinones, 29, 30 Camphene, arylation by arenediazonium tetrafluoroborates, 239 Carbazoles, synthesis from 2azidobiphenyl, 323 Carbodiimides, synthesis from arylisocyanates, 88 Carbonitriles, arylation, 218 1-(3-Carboxy-5-methylphenyl)-3, 3dimethyltriazene, synthesis from anilines/dimethylamine, 327 1-(4-Carboxyphenyl)-4, 5-dihydro-3, 5, 5trimethylpyrazole, 282 4-Carboxyphenylhydrazinium chloride, reaction with 4-methylpent-3-en-2one, 282 Cascade reactions, 65 Catechol, reaction with benzene diazonium chloride, 219 Catechols, oxidative cleavage, 28 -, pulse radiolysis, 31 Chloranil, reactions with aziridines, 23, 24 -, - with phenylcyclopropane, 24, 25 Chloroacetoacetanilides, reactions with benzenediazonium chloride, 251

N-Chloroanilides, oxidants for arylamines, 85 Chloroarenerutheniumcyclopentadienyls, 176, 177 Chlorobenzene, synthesis from aniline, 246 Chlorobenzeneironcyclopentadienyl cations, reactions with nucleophiles, 173-175 N-Chloro-1, 4-benzoquinone monoimines, hydroxyarylation, 47 Chloro-1, 4-benzoquinones, electron transfer from thiathrene, 22 N-(~-Chlorobenzylidene)benzenesulphonimide, reaction with ammonium thioisocyanate, 297 3-Chloro-4, 4'-dimethylazobenzene, 235 Chloroestrones, metal complexation, 178 6-Chloro-2-ethoxycarbonyl-7-methoxy- 1phenylindole, 270 4-[N-(2-Chloroethyl)amino]-5-methoxy1, 2-benzoquinone, 11 3-(2-Chloroethyl)indazoles, synthesis from 2-aminoaryl chloroalkyl ketones, 252 3-(2-Chloroethyl)-l-phenylindole, synthesis from cyclopropanone, 271 1-[4-(N-Chloroformyl-N-methylamino)phenyl]-2-(phenylsulphonyl)diazenes, as bifunctional reagents containing a protected diazonium group, 237 Chlorogermanes, 137, 138 3-Chloro-4-methylazobenzene, 235 4-Chloromethylazobenzene, 235 4-Chloro-4'-methylazobenzene, 235 4-Chloromethyl-4'-methylazobenzene, 235 Chloromethylnitroarenes, 63 2-Chloro-1, 4-naphthoquinone, chlorine displacement, 20, 21 2-Chloro- 1, 4-naphthoquinones, nucleophilic substitution, 1 2-Chlorophenols, synthesis from benzenediazonium salts, 246 2-(4-Chlorophenylamino)- 1, 4benzoquinones, 224 2-Chloro-l-phenylbenzimidazole, 232 1-Chloro- 1-(phenylhydrazono)propan-2-

354 one, cyclocondensation with thiourea, 285, 286 4-Chlorophenylthiobenzene, synthesis from benzenediazonium salts, 248 Chlorosilanes, 138 Cinnamate esters, synthesis by arylation of acrylates, 239 Cinnamonitriles, synthesis by arylation of acrylonitrile, 239 N-Cinnamoylarylamines, 281 rl6-Complexes, arenes, 152 Cortisone, synthesis, 40 Coumarins, synthesis from hydroxycinnamates, 38 Curtius rearrangement, 84 Cyanoacetamide arylhydrazones, cyclisation, 279, 280 3-Cyano-3H-azepin-2(1H)-one, 319 7-Cyano-3H-azepin-2(1H)-one, 319, 320 Cyano- 1, 4-benzoquinones, 17 1-(a-Cyanobenzylidene)-3phenyltriazene, reactions with nucleophiles, 332 5-Cyano-1, 3-diphenylcyanopyrazoline, 293 5-Cyanomethyl-4-hydroxy- 1phenylpyrazole, 274 5-Cyano-2-oxopent-3-enal phenylhydrazone, 274 1-Cyano- 1-trimethylsilyloxycyclohexa2, 5-dien-4-one, 8 Cyclic formazans, synthesis from aldimines/4,4'biphenylbis(diazonium) chlorides, 317 Cyclic sulphones, thermolysis, 39 (y6-Cyclobutabenzene) complexes, deprotonation-electrophile quenching, 202 Cyclobutanetetraone tetrakis(phenylhydrazone), 261, 262 Cycloheptene, reaction with N-nitrosoN-phenylacetamide, 216 Cyclohexadienemanganesenitroso_ dicarbonyls, 154 Cyclohexadienemanganesetricarbonyls, 153, 158, 159 Cyclohexadienemolybdenum, reactions with nucleophiles, 159

Cyclohexadienerheniumnitrosodicarbonyls, 154 Cyclohexadienes, synthesis from arenemanganesetricarbonyl complexes, 153 Cyclohexadienyliron complexes, reactions with nucleophiles, 159 Cyclohexan-1, 2-dione bis(Narylhydrazones), oxidative cyclisation, 291 Cyclohexane-3-spiro-3, 4-dihydro-1, 2, 4benzotriazine, 299, 300 Cyclohexane-3-spiro-1, 2, 3, 4tetrahydro-1, 2, 4-benzotriazine, tautomerism, 299, 300 Cyclohexane-1, 2, 3-triones tris(Narylhydrazones), cyclisation to cyclohexanotriazoles, 291 Cyclohexanone 2-aminophenylhydrazone, tautomerism, 299, 300 Cyclohexanone 2, 4-dinitrophenylhydrazone, attempted indolisation, 270 Cyclohexanotriazoles, synthesis from cyclohexane-1, 2, 3-triones tris(Narylhydrazones), 291 Cyclohexenones, synthesis from arenemanganesetricarbonyl complexes, 153 Cyclopentadienylbismuth complexes, 148 Cyclopentadienylsodium, reaction with arene-antimony complexes, 145 Cyclopenta[a]indanones, 208 Cyclophane iron complexes, 169 Cyclophane ruthenium complexes, 169, 170 Cyclophanes, methods of synthesis, 44 -, silicon containing, 129 -, tetrasubstituted, 249 Decanitrobiphenyl, 59 Dendritic molecules, 179, 180 3, 4-Diacetyl- 1, 6-bis(4-chlorophenyl)1, 5-hexaazadiene, X-ray crystal study, 335 1, 1-Diacetyl-2-phenylhydrazine, synthesis from phenylhydrazine/ acetic anhydride, 257

355 1, 1-Diacyl-2-arylhydrazines, 312 3, 5-Diacylpyrazoles, 275 4, 5-Dialkoxy-1, 2-benzoquinone, nucleophilic addition reactions, 11 N, N-Dialkyanilines, dealkylation, 81 5-Dialkylamino-2-aryl-4-cyano-1, 2, 3triazoles, synthesis from malononitrile arylhydrazones/amines, 291 N,N-Dialkylanilines, synthesis from anilines, 79 from enamines, 82 3, 3-Dialkyl-l-aryl-triazenes, as carcinogens, 326, 327 3, 3-Dialkyl-l-arylureas, N-nitrosation, 215 4, 4'-Dialkylazoxybenzenes, liquid crystallinity, 233 1,1-Dialkyl-2, 3, 4, 5-tetraarylstannoles, reactions with arylboron dichlorides, 125 2, 2-Diamino-l-arylazoethenes, synthesis from 2-aryl-1,1dichloroazoethenes, 221, 222 2, 2'-Diaminoazobenzene, synthesis from 1, 2-diaminobenzene, 225 2, 4-Diaminoazobenzene, synthesis from benzenediazonium salts, 253 1, 2-Diaminobenzene, synthesis from aniline, 225 1, 3-Diaminobenzene, charge-transfer complexes, 77 1, 2-Diaminobenzenes, 'SNMR spectra, 77 Diaminobenzophenones, synthesis from methyl N-arylcarbamates, 91 4, 4'-Diamino-3, 3'-dimethylbiphenyl, 234, 235 2, 9-Diamino-9-ethoxycarbonyl-6methoxy-1, 3, 5, 7-tetramethylfluorene, 265 4, 4-Diamino-2, 2', 3, 3', 5, 5', 6, 6'octachloroazobenzene, deamination, 227 Diarylamines, synthesis from arenes/ nitrenium anions, 81 from 1-aryl-2-ethoxycarbonyl-4, 6diphenylpyridinium salts, 81 Diaryl(arylethynyl)boranes, 123

N,N-Diarylbenzylamine, synthesis from N-(arylmethylene)arylamines, 80 1, 5-Diaryl-3-'butyl-1, 2, 4-triazoles, synthesis from 1-(N-arylhydrazin2-yl)- 1-imino-2, 2-dimethylpropanes/ araldehydes, 294 Diarylcarbodiimides, synthesis from iminophosphoranes, 91 -, -from thioureas, 91 1, 2-Diaryldiazene oxides, azoxyarenes, 232 1, 2-Diaryldiazenes, azoarenes, 224 2, 5-Diaryl-3, 6-di(ethoxycarbonyl)-l, 4dihydro-1, 2, 4, 5-tetrazines, 308 1, 3-Diaryl-3a, 7b-dihydro-lHbenzo [c] [1, 2, 4]triazole, synthesis from pyridine and diphenylnitrilimine, 307 Diaryl ethers, methods of synthesis, 175, 265 -, synthesis from 4-hydroxyacetophenones, 265 Diarylhydroxylamines, synthesis from N-nitrosodiphenylamine, 69 N, N-Diarylhydroxylamines, oxidation, 69 1, 5-Diaryl-3-(methylthio)formazans, structural analyses, 318, 319 Diarylnitroxides, synthesis from N,Ndiarylhydroxylamines, 69 2, 4-Diaryl-4, 5, 6, 7-tetrahydrobenzotriazoles, synthesis from cyclohexan-1, 2-dione bis(Narylhydrazones), 291 Di(aryl) tetrasulphides, 258 1, 3-Diaryltriazenes, 88 -, synthesis from arylisocyanates/ tetraethylammonium nitrite, 330 1, 5-Diaryl-3-trifluoromethyl1,2, 4-triazoles, synthesis from arylydrazines, 294 Diarylureas, transamination, 90 N, N-Diarylureas, 90 Diazaboridines, stability, 124 Diazenes, synthesis from benzenediazonium sulphate, 227, 228 4, 4'-Di(azido)biphenyl, photolysis, 319, 320

356 Diazoamino compounds, aryltriazenes, 326 4-Diazophenol, 247 Diazophenols, 58 Dibenzyl ketone 4-nitrophenylhydrazones, oxidative coupling, 263, 264 5, 5-Dibromo-2, 2-dimethyl-1, 3-dioxane4, 6-dione, 75 ~, ~'-Dibromo-1, 2-xylene, Finkelstein elimination, 38 2, 6-Di-'butyl-1, 4-benzoquinone, 6 3, 5-Di-'butyl-1, 4-benzoquinone, 29 3, 5-Di-'butyl-1, 2-benzoquinone, nucleophilic addition reactions, 11 -, reaction with 1, 3-dienes, 20 3, 5-Di-'butylcatechol, ring cleavage, 29 2, 6-Di-'butyl-4-methylphenol, reaction with acetonylacetone/manganese(II) acetate, 43, 44 2, 4-Di-'butyl-6-methyl Nthiosulphinylaniline, 92 2, 6-Di-'butyl-4-nitrophenol, synthesis from 2, 6-di-'butyl-4-nitrocyclohexa2, 5-dienone, 57 4, 4'-Dichloroazobenzene, 224 Dichlorobenzeneironcyclopentadienyl cations, reactions with nucleophiles, 174-176 Dichloro-1, 4-benzoquinones, 13, 14 2, 3-Dichloro-1, 3-butadiene, reaction with benzenediazonium chloride, 240, 241 2, 3-Dichloro-5, 6-dicyano-1, 4benzoquinone (DDQ), 4, 5, 16 -, cycloaddition reactions with cyclopentadiene, 16, 17 2, 3-Dichlorohydroquinone, 13, 14 2, 2'-Dicyanoazobenzene, 229 N, N-Dicyano- 1, 4-benzoquinone diimines, 48 Didehydroazepine, 319, 320 Dienone-phenol rearrangements, 51 Diethoxy tetrasulphide, 258 Diethylanilines, synthesis from aryl bromides, 81 Diethyl 2-cyano-3-methylpent-2-en-1, 5dioate, reaction with arenediazonium chlorides, 287

N, N', N, N'-Diethyldiphenylurea, synthesis from aniline/urea]diethyl sulphate, 90 Diethyl 2-formylmalonate phenylhydrazone, 227, 228 Diethyl 2-oxocyclohexane- 1, 4dicarboxylate, reaction with phenylhydrazine, 284 Diethylphenylamine, coupling with arenediazonium chlorides, 225 Digermanes, photolysis, 137 9, 10-Dihydroacridines, synthesis from 2-azidophenyl)phenylmethane, 323 2, 3-Dihydrobenzofurans, synthesis from 2-(O-allyl)benzenediazonium tetrafluoroborates, 243 , from hydroxy-1, 4-benzoquinones, 24, 25 4, 5-Dihydro-lH-1, 3, 4-benzotriazepines, synthesis from 1-aryl-2-iminodiazenes, 221 1, 4-Dihydro-2, 3-benzoxathiin 3-oxide, thermolysis, 38, 39 Dihydrodioxins, 19-21 3a, 9b-Dihydro-1, 3-diphenyl-lHnaphtho [1, 2-c] [1, 2, 4]triazole, synthesis from isoquinoline and diphenylnitrilimine, 307 3, 4-Dihydroisocoumarins, 39 Dihydroisosilabenzofurans, 24, 25 5, 8-Dihydro-1, 4-naphthoquinone, 18 1, 3-Dihydro- 1-phenyl-3phenylcarbamoyl-benzimidazol-2ones, 322 2, 3-Dihydro-5-phenylsulphonamidoindoles, 48 5, 10-Dihydro-2, 5, 7, 10-tetramethyl5, 10-phenazine, 334 Dihydrotriazaphospholes, synthesis from aryl azides, 323 2, 5-Dihydroxybenzenesulphinic acid, 8 2, 5-Dihydroxybenzenesulphonic acid, 8 3, 4-Dihydroxymandelic acid, autoxidation, 28 3, 4-Dihydroxyphenylacetic acid, autoxidation, 28 3, 4-Dihydroxyphenylalanine, autoxidation, 28

357 1, 2-Diisocyanatobenzenes, synthesis from 1, 2-diamidobenzenes, 91 4, 4'-Di(isocyanato)biphenyl, 319 Dilithium pentalenide, 99 Dimethyl 2-amino-5-hydroxyethoxyterephthalate, diazotisation and intramolecular cyclisation, 238 2, 6-Dimethylaniline, oxidation with hydrogen peroxide/sodium tungstate, 233 N,N-Dimethylanilines, synthesis from nitroarenes/methanol, 82 2, 2'-Dimethylazobenzene, synthesis from 2-methylnitrobenzene, 224 4, 4'-Dimethylazobenzene, 235 2, 2'-Dimethylazoxybenzene, nitration, 234 4, 4'-Dimethylazoxybenzene, 235 2, 3-Dimethyl-1, 4-benzoquinone, 14 Dimethyl-1, 4-benzoquinones, 29 N, N-Dimethylbenzylamine, reaction with butyllithium, 101 5, 5-Dimethyl-2, 4-diphenyl-l-(Nphenylaminocarbonyl)triazolidin3-one, 295, 296 5, 5-Dimethyl-2, 4-diphenyltriazolidin-3one, 295, 296 (r/6-O,N-Dimethylephedrine )chromiumtricarbonyl complex, deprotonationalkylation, 203 1, 2-Dimethyl-8-methylaminonaphtho[3, 2, l-c, d]indol-10-one, 273 2,2'-Dimethyl-4'-nitroazoxybenzene, 234 2, 6-Dimethyl-4-nitrophenol, synthesis from 4-nitrocyclohexadienones, 56 3, 5-Dimethyl-4-phenylazo- 1(N-phenylthiocarbamoyl)pyrazole, synthesis from 2,3, 4pentanetrione 3-phenylhydrazone/ 1-phenylthiosemicarbazide, 277 1, 2-Dimethyl-l-phenylhydrazine, dehydrodimerisation, 259 3, 3-Dimethyl-l-phenyltriazene, metabolism, 327 2, 3-Dimethyl-l-trimethylsilylbut2-ene, reaction with 2,4dinitrobenzenediazonium tetrafluoroborate, 239 4, 4'-Di(nitreno)biphenyl, 319, 320

3,3-Dinitroazobenzene, synthesis from 3-nitroaniline, 224 2, 4-Dinitrobenzene sulfonic acid, synthesis from 2, 4-dinitrochlorobenzene, 61 2,2'-Dinitrobiaryls, synthesis from 2-halogenonitrobenzenes, 62 2, 4-Dinitro-(2, 3-dimethylbut- 1-en-3yl)benzene, 239 2, 4-Dinitrofluorobenzene, vicarious nucleophilic substitution, 63 Di(4-nitrophenyl) disulphide, 258 2, 4-Dinitrophenylhydrazones, 261 -, reduction to 2,4diaminophenylhydrazines, 264 Dioxazolidines, synthesis from phenylhydroxylamines, 69 (~6.1, 2-Dioxobenzocyclobutane)chromiumtricarbonyl complexes, double anionic oxy-Cope rearrangements, 208 Dioxolanones, synthesis from arylisocyanates, 88 (~6_1, 3-Dioxol-2-ylarene)chromiumtricarbonyl complexes, ortho metallation, 190, 191 Diphenylamines, chlorinated, formation in Fischer indolisation reaction, 270 Di(N-phenylamino)methylimine, 225 Diphenylcyclopropenone, ring opening by arylhydrazines, 280 1,1-Diphenylethene, 216 Diphenylfluoroarsonium hexafluoroarsenate, 145 1, 2-Diphenylhydrazines, synthesis from nitrobenzenes, 311 N, N-Diphenylhydrazones, reactions with chlorocarbonylsulphenyl chloride, 286 Diphenylmethanes, benzylic alkylation, 205 1, 5-Diphenyl-3-(4-methoxyphenyl)formazan, oxidative cyclisation, 316 Diphenylnitrilimine (Ph CN§ ground state structure, 302 -, reactions with tetrazol-5-yl-Nsulphonylimines, 310 , with benzaldehyde phenylhydrazone, 302

358 Diphenylnitrilimine, reactions (cont'd) -, - with benzenesulphonyl isocyanate, 308 -, synthesis from 2, 5-diphenyltetrazole, 302 , from N-phenylbenzohydrazonoyl chloride, 307, 308 1, 3-Diphenylnitrilimine, generated from N-phenylbenzohydrazonoyl chloride/ triethylamine, 293 a,N-Diphenylnitrones, synthesis from anilines, 66 from nitrobenzene/benzaldehyde, 69 1, 2-Diphenyl- 1-(phenylazo)ethene, reactions with alkanols, 219, 220 O-(Diphenylphosphinyl)hydroxylmine, aminating agent, 73 N- [(Diphenylphosphinyl )oxy]arylamines, reactions with Nmethylaniline, 225 Diphenylphosphorazidate, amiaating agent, 73 Diphenylsulphur diimides, 92 2, 4-Diphenyl-5-(tetrazol-5-yl)-l, 2, 3, 5thiatriazole S-oxides, 310 1, 3-Diphenyltriazene, N-acylation, 333 -, alkylation, 333 -, fragmentation into phenyl radicals, 333 1, 5-Diphenyl-1, 2, 4-triazoline-3-thione, 297 N,N'-Diphenylurea, crystal structure, 90 -, reaction with benzoin, 90 1, 3-Diphenyl-5-vinyl-1, 2, 4-triazole, synthesis from 1-benzyl-2phenylhydrazine/acrylonitrile, 293 1, 4-Di(ipropyl)benzene, 31 4, 4'-Disubstituted azoxybenzenes, rearrangent, 235 a,w-Di(tetrazolyl)alkanes, 254, 255 Dopaquinone, 2, 11 Duroquinone, 5 Electron storage systems, 26 Electron transfer, 1, 4-benzoquinones, 22 Electron transfer systems, 26

Estrones, metal complexation, 178 I~tard adducts, hydrolysis to azobenzenes, 224 Ethene, phenylation by benzenediazonium tetrafluoroborate! bis(dibenzylidene acetone)palladium, 239 2-Ethoxycarbonylcyclopentanone, 2arylation, 144, 145 6-Ethoxycarbonyl-3, 3a, 4, 5, 6, 7hexahydro-2-phenylindazol-3(2H)one, 284 2-Ethoxycarbonyl-7-methoxy-1phenylindole, 270 2-(E thoxycarbonylmethyl)- 1phenyldiazene 1-oxide, 301 3-Ethoxycarbonyl-l-phenyltriazene, 330 1-Ethoxycarbonyl-3, 4, 4a, 5tetrahydropyrimidino[4, 5-c]-1, 4benzoxazine, 290 Ethoxy 4-nitrophenyl tetrasulphide, 258 Ethyl 2-[N-(2-(2-allyloxy)phenyl] hydrazono]-2-azidoacetate, thermolysis, 290, 291 Ethyl (4'-amino-5-methoxy-3', 4, 5, 5'tetramethylbiphenyl-2-yl)glyoxylates, 265 4-(N-Ethylamino)pyridine, synthesis from 1-phenyl-2-(4-pyndyl)hydrazine, 312 N-Ethylaniline, synthesis from hydrazobenzene, 312 Ethyl 2-chloro-2-(phenylhydrazono)acetate, 301 Ethyl cinnamate, synthesis from ethyl acrylateJphenylazoxy phenyl sulphone, 218 Ethyl 4, 4-dicyano-3-methylbut-3eaoate, reaction with arenediazonium chlorides, 252 2-Ethyl-2'-hydroxybiphenyl, 247 3-Ethylindole, 279 N-Ethylnylanilines, synthesis from isoxazolones, 82 2-(2-Ethylphenyl)benzenediazonium chloride, dediazoniation, 247 Ethyl phenylcarbamate, N-alkylation, 90 (~6-2-Ethylpyridine)chromium-

359 tricarbonyl complex, deprotonationhydroxyalkylation, 206 Ethyl pyruvate N~-phenyl2-methoxyphenylhydrazone, indolisation, 269, 270 Ferrocene, 165 Fischer-Hepp rearrangements, 84, 216 Fischer indole synthesis, 256, 269-272 Fluorene, lithiation, 98 Fluoroarenes, synthesis from nitroarenes, 62 Fluorobenzenes, synthesis from arenediazonium salts, 245, 246 5-Fluoro-1, 3-dimethylimidazole, 144 4-Fluorophenols, synthesis from 4aminophenols, 246 Formanilide, rotomers, 85 -, synthesis from aniline/ pentafluorophenyl formate, 84 , from nitroarenes, 84 from phenylazide/acetaldehyde, 84 Formazans, complexes with divalent metal ions, 318 , with trivalent metal ions, 318 -, physical properties, 318, 319 -, reactions, 318, 319 -, synthetic methods, 313 Furan-2-yl phenyl ketone 4nitrophenylhydrazone, 279 Furoyl chloride, arylation, 141, 142 Glyoxal arylhydrazones, reactions with aniline, 330 Gomberg-Bachmann arylation, 238, 239 Grignard reagents, 112-116 (~6-Haloarene)chromiumtricarbonyl complexes, 190 -, nucleophilic substitutions, 196, 197 Halogenoarenes, 236 -, amination, 72 -, synthesis from arenediazonium salts, 245, 246 Halogenonitroarenes, nucleophilic substitution, 61 Heck reaction, 151 3-Heteroarylpyrazolines, 281, 282 Heterobimetallic complexes, 205

Heterocycles, synthesis from benzenediazonium salts, 250 Heterotrimetallic complexes, 205 Hexabutyltin, reaction with aryl iodides, 140 Hexakis(phenylethyl)benzene, metal complexation, 166 Hexakis(trimethylsilyl)benzene, lithiation, 96, 98 1, 2, 3, 4, 5, 6-Hexakis(trimethylsilyl)cyclohexa-1, 4-diene, 98 Hexamethylbenzene, metal complexation, 166, 167 -, reaction with nitronium tetrafluoroborate, 58 (~6-Hexamethylbenzene)iridiumcyclopentadienyl complex, 212 Hexamethylbenzeneironcyclopentadienyl cation, alkylation, 179, 180 Hexamethylbenzenemanganesetricarbonyl complex, deprotonation, 162 (r/6-Hexamethylbenzene)rhodiumcyclopentadienyl complex, 212 1,1, 2, 2, 3, 3-Hexamethylbenzosilacyclopentane, 131 Hexamethylsilirane, reactions with benzyne, 131 Hexanitrobenzene, 58 Homobenzoquinones, methods of synthesis, 48, 49 Homo-l, 4-benzynoquinone, reaction with anthracene, 49 Hydrazobenzene, hydrogen transfer from propan-2-ol, 312 -, reaction with diethoxydisulphide, 312 , with potassium ethoxide, 312 -, synthesis from azobenzene, 234 -, - from azoxybenzene, 234 Hydrazobenzenes, synthesis from azoarenes, 229 -, - from azobenzenes, 311 Hydrazo compounds, synthesis from N-methylaniline, 226 Hydroquinone, industrial preparation, 30, 31 Hydroquinone diethers, anodic oxidation, 50, 51

360 Hydroquinones, autoxidation, 30 -, pulse radiolysis, 31 Hydroquinone sulphinic acid, 8 Hydroquinone sulphonic acid, 8 Hydroxamic acid derivatives, reactions with butylamine, 226 4-Hydroxyacetophenone 2, 6dimethylphenylhydrazone, rearrangement, 266 2-Hydroxyarylazo compounds, 235 2-Hydroxyazobenzenes, synthesis from azoxybenzenes, 235 3-Hydroxybenzotriazines, synthesis from aryltriazenes, 328 Hydroxycalix[4]arenes, reactions with 4-nitrodiazonium salts, 249 Hydroxycyclohexadienones (benzoquinols), 2, 49, 50 4-Hydroxy-3, 5-dimethyloxyacetophenone 2, 6-dimethylphenylhydrazone, rearrangement, 266 2-(1-Hydroxyeth-2-yl)biphenyl, 247 Hydroxylamines, synthesis from nitroso compounds, 331 Hydroxymethyltriazenes, as potential cytotoxins, 327 1-Hydroxytetralins, 41 Imidazoles, synthesis from arylhydrazones, 284 Imidazolinones, synthesis via AzaWittig reactions, 285 (Imino ~6-arene)chromiumtricarbonyl complexes, cycloadditions, 209 -, reactions with nucleophiles, 210 2-Imino-3-phenyl-5-trifluoromethyl1, 3, 4-thiadiazoline, 309 (~6-Indane)chromiumtricarbonyl cations, nucleophile quenching, 206 Indazole-3-carboxylic acid, synthesis from phenylhydrazine/chloral hydrate/hydroxylamine hydrochloride, 284 Indazoles, synthesis from 1-(2acylphenyl)-2-aryldiazenes, 229 , from aryhydrazones, 284 - , - from benzenediazonium salts, 251, 252

from 1-(2-methylphenyl)diazenes, 221 Indenones, synthesis from rl1areneirondicarbonyl complexes, 163 Indenylsodium, reaction with areneantimony complexes, 145 Indole-4, 7-quinones, 35, 36 Indolerutheniumcyclopentadienyls, 178, 179 Indoles, synthesis from arylhydrazones, 269-272 - , - from benzenediazonium salts, 250, 251 2-Iodoanilides, radical formation by 1, 5-H transfer, 86 2'-Iodo-2- [N~-(4-methylphenylazo)]biphenyl, cyclisation to N-(4-methylphenylamino)carbazole, 229, 230 2'-Iodo-2- [N~-(4-methylphenylhydrazino)]biphenyl, 229, 230 2-Isocyanatobenzoyl chloride, 88 N-(a-Isothiocyanatobenzylidene)benzenesulphonamide, reaction with phenylhydrazine, 297 Isoxazolidines, synthesis from phenylhydroxylamines, 69 2-Isoxazolines, synthesis from styrenes, 209 Janovsky complexes, aromatisation, 60 Ketene silyl ketals, a-arylation, 240 a-Ketoaldehydes arylhydrazones, reaction with N-bromosuccinimide, 301 Kundig ligand transfer, 188, 189 Lignins, biosynthesis, 36 -, degradation, 29 1-Lithio-2-(lithiomethyl)benzene, 107109 2-Lithio-N-methyl-N-oxypropylaniline, reactions with electrophiles, 83 1-Lithio-2-[(trimethylstannyl)methyl]benzene, 107-109 Lithium 2, 5-dimethylstilbacyclopentadienide, reaction with cyclopentadienyl complexes, 147, 148 Lutidine osmium complexes, 184, 185

361 3, 4-Mandeloquinone, 31 Mauveine, proof of structure, 75 Mebendazole, 91 Meisenheimer complexes, nitroarenes, 60 Meisenheimer rearrangements, 84 Melanins, biosynthesis, 35, 36 Melanogenesis, 11 [2.2]Metacyclophane, difunctionalisation, 203 [2.2] Methacyclophanes, diazotisation, 250 Methoxy-1, 4-benzoquinone, crystal assembly, 25, 26 -, reaction with propenylbenzene, 18 2-Methoxy-1, 4-benzoquinones, 29 2-Methoxycarbonyl-l-tetralol, 39 7-Methoxy-2H-chromene, 18, 19 2-Methoxy-5-methyl- 1, 4-benzoquinone, cycloadducts, 16 N-(Methoxymethyl)-N-phenylamine, 79 4-Methoxyphenol-sorbyl alcohol, oxidation, 51 5-(4-Methoxyphenyl)-2, 3-diphenyltetrazolium tetrafluoroborate, reaction with bases, 315 3-(4-Methoxyphenylhydrazono)-4methylpiperidin-2-one, indolisation, 273 Methyl acrylates, reactions with arenediazonium tetrafluoroborates! N,N-diethyldithiocarbamic acid salts, 242 Methyl N-arylcarbamates, reactions with phosphorus pentachloride, 90 Methyl- 1-aryltriazenyl-3-carbonitriles, synthesis from arylazides, 328 4-Methylazobenzene, 235 4-Methylazoxybenzene, 235 2-Methyl-I, 4-diaminobenzene, 234 10-Methyl-9, 10-dihydroacridine, 60 5-Methyl-2, 3-diphenyltetrazolium hydrogenselenite, synthesis from phenylhydrazine, 317, 318 N-Methylenearylamines, stability, 79 9-Methylfluorene, 247 N-(Methylidene)aniline, 225 2-Methylindanone, reaction with 4-

methylphenylhydrazine/acetic acid, 271 3-Methylindazole, synthesis from ethyl N-(cyanoacetyl)carbamate, 284 1-Methyl-2-methylthiobenzene, dilithiation and reaction with electrophiles, 103-107 5-Methyl-l-(4-nitrophenyl)-3phenylfurano [2,3-c]pyrazole, 279 7-Methyl-2-(2-nitrophenyl)pyrazolo [3, 4d]pyridazines, 303, 304 4-Methyl-4-nitro-2, 3, 5, 6tetrabromocyclohexa-2, 5-dienone, 58 S-Methyl-N-nitrothiourea, reaction with phenylhydrazine, 260 3-Methylpentane-2, 4-dione bis(Narylhydrazones), oxidation, 277, 278 4-Methyl-3-penten-2-one, reaction with arenediazonium tetrafluoroborates, 240, 241 c~-Methylphenylacetaldehyde, synthesis from propen-2-enol, 240 (,7~-Methyl phenylacetate)chromiumtricarbonyl complex, benzylic alkylation, 205 N-(4-Methylphenylamino)carbazole, 229, 230 2-Methyl-2-phenyl- 1-arylhydrazines, synthesis from N-arylcarbamates, 310, 311 Methyl N-phenylcarbamates, benzoylation, 90, 91 1-Methyl- 1-phenylhydrazine, 257 2-Methyl-l-phenylhydrazines, reactions with fumaric acid, 268 , with maleic acid, 268 , with methyl acrylate, 268 et hyilh s t yrene, 268 2-(N-phenylhydrazono)-2[(triphenylphosphoranylidene)amino]acetate, 293 N-(4-Methylphenyl)methylamino radicals, dimerisation, 334 1-(4-Methylphenyl)-3-methyltriazene, alkylation, 333 5-Methyl- 1-phenylpyrazole, 279 3-Methyl- 1-phenyltriazene, 327

362 (~5_1-Methylpyrrole)chromiumtricarbonyl complex, 187 2-(2-Methyltetrazol-5-yl)hydrazone/ arenediazonium chlorides, 314 1-Methyl-4-trimethylsilylnaphthalene, Birch reduction, 135, 136 Methyltriphenyltin, reaction with furoyl chloride, 142 =Misorientated" Birch reductions, 135, 136 Mitomycins, 35, 36 Muconic acids, formation from catechols, 28, 29 Multidentate formazans, synthesis from bis(benzenediazonium) ethers, 317 Naphthalene, lithiation, 98 -, reaction with antimony trichloride, 145 (y~-Naphthalene)chromiumtricarbonyl, ligand exchange reagent, 186 Naphthalenes, Birch reduction, 135, 136 Naphthophenothiazines, 324 1, 4-Naphthoquinones, 14, 15 5, 8-Naphthoquinones, 14, 15 Neber rearrangement, 73 Neolignans, 35, 36 Nitrenium ions, generation, 68 Nitrilimines, additions to imines, 306 -, cycloaddition reactions with 1, 4benzoquinones, 305 -, kinetic properties, 302 -, reactions with alkenes, 303 , with alkynes, 303 -, spectra, 302 -, synthesis from hydrazonoyl halides, 301, 302 - , - from tetrazoles, 302 1-Nitroamino-2, 3-diaminoarenes, rearrangement reactions, 236, 237 3-Nitroaniline, oxidation by bipyridyl silver permanganate, 224 Nitroarenes, alkylation, 61 -, amination, 63 -, hydrogenation, 70-72 -, hydroxylation, 63 -, nucleophilic substitution, 61 -, photochemical reduction, 60 -, reduction to anilines, 70-72

-, reductive carbonylation, 63, 90 -, synthesis from anilines, 59 , from benzenediazonium salts, 247 -, vicarious amination, 73 4-Nitroarylhydrazines, decomposition to 4-nitroaryl radicals, 259 4-Nitroaryl radicals, 259 Nitroaryltriflates, nucleophilic substitution, 62 4-Nitroazidobenzene, reduction, 320 Nitrobenzene, Friedel-Crafts reactions, 61 -, radical anion, 60 -, reduction to aniline, 63 4-Nitrobenzenediazonium tetrafluoroborate, reaction with sodium, 247 4-Nitrobenzenediazotate, 247 Nitrobenzenes, reduction to azoxyarenes, 232 Nitro-l, 4-benzoquinones, 17 4-Nitrobiphenyl, 258 Nitrodiazophenols, synthesis from anilines, 236, 237 4-Nitrophenol, synthesis from benzenediazonium salts, 247 2-Nitrophenols, nitration, 56 2-(2-Nitrophenyl)azoarenes, synthesis from arenediazonium tetrafluoroborates, 227 1-(4-Nitrophenylazo)- 1hydroperoxyphenylethanes, 262, 263 1-(4-Nitrophenylazo)-lperoxycobalt(III)ethylbenzene complexes, 262, 263 2-[(2-Nitrophenyl)azo]phenols, reactions with thioureas, 230 N-(4-Nitrophenyl)-N'N'-dimethylurea, synthesis from 4-nitroazidobenzene, 321 4-Nitrophenylhydrazine, reaction with diethoxy disulphide, 258 4-Nitrophenylhydrazones, oxidation by 'butylperoxy(N,N'disalicylidenediaminato)cobalt, 263 -, oxygenation, 262 1-[N-(2-Nitrophenyl)hydrazono]-lchloropropan-2-one, reaction with ethyl cyanocyanate, 303

363 1-(4-Nitrophenyl)-3-phenylfurano[2,3c]pyrazole, 279 N-(4-Nitrophenylthio)-2, 4, 6'butylphenylaminyl radical, 92 N-Nitropyridinium salts, as nitro group-transfer reagents, 58 2-Nitro-N-(pyrid- 1-yl)aniline zwitterion, 233 N-Nitroquinolinium salts, as nitro group-transfer reagents, 58 Nitrosoarenes, as spin traps, 65 -, Diels-Alder reactions, 65 -, mutagenicity, 65 -, pre-equilibration with arylhydroxylamines, 67 -, reductive carbonylation, 66 -, synthesis from anilines, 64 - - from nitronates, 61 4-Nitrosoarylamines, 216 Nitrosobenzene, reaction with benzothiete, 65 -, - with 2-diphenylmethylene-1, 3cyclopentadienyl diradical, 66 -, - with ethyl N,Ndibromoaminoacetate, 301 , with N-ethoxycarbonylhydrazine, 330 , with pyran-2-thione, 66 -, synthesis from nitrobenzene, 64 Nitrosocarbonylarenes, Diels-Alder reactions, 65 Nitroso compounds, reactions with arylhydrazines, 331 N-Nitrosodialkylamines, 216 Nitrosodimethylaniline, EDAcomplexes, 65 N-Nitroso-N, N-diphenylamine, synthesis from N-chloroformyl-N, Ndiphenylamine, 215 Nitrosonium salts, charge-transfer complexes, 55, 56 2-Nitrostilbenes, structure, 60 Nitrotoluenes, relative acidities, 60 2, 2', 3, 3', 5, 5', 6, 6'-Octachloroazobenzene, synthesis from 1, 4diamino-2, 3, 5, 6-tetrachlorobenzene, 227 1-Octene, 216

Organosilicon iodides, solvolysis, 134, 135 Orton rearrangement, 86 Oxadiazole, synthesis from diphenylnitrilimine, 308 1,3-Oxathiol-2-ones, synthesis from N, N-diphenylhydrazones, 286 Oxazolidines, synthesis from ureas] hydroxybutanones, 90 2-Oxazolidinones, as aziridine equivalents, 82 2-(3-Oxobutanoyl )- 1-methyl- 1phenylhydrazine, reaction with phosphoric acid, 272, 273 2-Oxomalonic acid phenylhydrazone, reaction with hydroxylamine, 311 Paracetamol (acetaminophen), 86 -, bio-oxidation, 47 Paracyclophanes, pyrolysis, 44 Pentaazadienes, synthesis from arenediazonium salts/amine, 327, 328 Pentamethylcyclopentadienylruthenium cyclophane complexes, 170, 171 Pentamethyldisiloxanes, reactions with benzene, 130, 131 Pentane-2, 4-dione, reaction with arenediazonium chlorides, 251 Pentane-2, 3, 4-trione 3(arylhydrazones), cyclisation to 3-acetyl- 1-aryl-5-chloro-4, 5-dihydro4-methylpyridazin-(5(1H)-ones, 288 2, 3, 4-Pentanetrione hydrazones, 277 Pentanitroaniline, synthesis from 4amino-2, 6-dinitrotoluene, 58 Pentarylboroles, methods of synthesis, 125 -, reactions, 125 4-Pentylaniline, 233 Perchloroazobenzene, synthesis from 1, 4-diamino-2, 3, 5, 6tetrachlorobenzene, 227 Perfluoroarylcadmiums, synthesis from bromofluoroarenes, 118 Phenacyl thiocyanates, reactions with arenediazonium chlorides, 249 Phenanthracene, reaction with antimony trichloride, 145

364 1, 4-Phenanthraquinones, method of synthesis, 18 Phenol-formaldehyde resins, 37 Phenols, amination, 72 -, mononitration, 57 -, synthesis from arylborons, 142 - , - from benzenediazonium salts, 247 Phenothiazine, synthesis from dichlorobenzeneironcyclopentadienyl cations, 176 Phenoxazines, synthesis from dichlorobenzeneironcyclopentadienyl cations, 176 (~6-Phenylacetal)chromiumtricarbonyl complexes, reactions with homoallyl alcohols, 207 Phenyl 2-acetyl-1, 4-dihydroxy-3sulphinate, 9 Phenylaminoanilines, 225 Phenylazide, photolysis, 319, 320 5-Phenylazo-6-arylidenehydrazino1, 3-dimethyluracils, reactions with dimethylformamide dimethylacetal, 222 Phenylazo-2, 4-cyclohexadien-l-ones, 219 1-Phenylbenzimidazol-2(3H)-one, 232 3-Phenyl-1, 2, 3-benzotriazin-4-one, 325, 326 3-Phenylcycloheptene, synthesis from cycloheptene, 216 1-Phenyl-3, 3-dimethyltriazene-2-oxide, synthesis from N-nitrodimethylamine/ aniline-N, N-dimagnesium bromide, 331 Phenylenediamines, commercial uses, 77 -, synthesis from dihalobenzenes, 77 , from hydrazones, 77 , from nitroarenes, 76, 77 -, use in heterocyclic syntheses, 78 1-Phenylethanolamines, 206, 207 Phenylglyoxal bis(4-nitrophenylhydrazones), 263, 264 Phenylhydrazine, methylation, 257 -, oxidation, 259 -, reactions with 5-alkylfuran-2(5H)ones, 269 -, - with ~-formyloxiranes, 276

, with fused pyrones, 275 , with 5-azido-2-furaldehyde, 274 - , - with 3-cyanochromone, 275 -, - with 2-cyano-3-ethoxypropenones, 283 2-[(2-Phenylhydrazin-l-yl)formo]benzimidazole, 284, 285 (2-Phenylhydrazin- 1-yl) glyoxalate, reaction with 1, 2-diaminobenzene, 284, 285 Phenylhydrazinylnitrourea, oxidation, 260 4-(2-Phenylhydrazin-l-yl)tetrahydrofuran-2-ones, 269 Phenylhydrazones, reactions with N,Ndimethylformamide under Vilsmeier conditions, 276 -, reductive dimerisation to 1, 2-bis(2phenylhydrazin- 1-yl)ethanes, 264 Phenylhydronitroxide radical, 67 Phenylhydroxylamine, anodic oxidation, 64 -, cycloaddition reactions, 69 Phenylisocyanate, conformation, 87 -, cycloaddition reactions, 88 -, laser-induced fluorescence spectrum, 88 -, reactions with butanol/anilines, 88 -, - with 1,1-dimethyloxirane, 88 Phenylisocyanates, reactions with formanilides, 85 Phenylisonitrile, 225 Phenyllithium, reaction with iron(II) chloride, 102 Phenylmercury chloride, 119 Phenylnitrene, generation from phenylisocyanate, 89 -, photoequilibration, 319 2-[1-Phenyl- 1-(N-phenylaminocarbonyl)hydrazono-2-yl]propane, 295 Phenyloctenes, synthesis from octene, 216 Phenylpotassium, 109 2-Phenylpropanal, synthesis from propen-2-enol, 240 1-Phenylpropane-1, 2-dione monoxime, 239 1-Phenylpyrazoles, 276

365 1-Phenylpyrazoles (cont'd) -, synthesis from phenylhydrazones, 276, 277 1-Phenyl-2-(4-pyridyl)hydrazine, reaction with potassium ethoxide, 312 Phenylsiloxanes, 130 1-Phenyl-2-sulphinylhydrazine, photolysis in aromatic solvents, 258, 259 Phenylsulphonyl-1, 4-benzoquinone, 8 N-Phenyltetrachloroaziridine, 232 Phenylthiomethylazide, aminating agent, 72 1-Phenyl-2, 3, 4-trichlorobut-2-ene, 240, 241 N-Phenyl-2, 2, 2-trifiuoroacetohydrazonoyl bromide, reaction with potassium isothiocyanate, 309 - - with sodium isocyanate, 309 3'-Phenyl-5-trifluoromethyl-1, 3, 4thiadiazolin-2-one, 309 2-Phenyl-5-trifluoromethyl-1, 2, 4triazolin-3-one, hydrolysis, 309 2-Phenyl-5-trimethylsilyl-1, 2, 3, 4triazaphosphole, 323, 324 N-Phenylureas, nitrosation, 90 N- Phenyl-O-vinylhydroxylamines, hetero Cope rearrangement, 68 Photo Fries rearrangement, 86 Plastoquinones, 6 Podocarpic acids, 164, 178 (~6_Polyarene)chromiumtricarbonyl

complexes, 188 Polycyanoarylhydrazobenzenes, synthesis from polycyanoaryl halides/ phenylhydrazine, 311 Polynitroarenes, 59 Polynitrobenzenes, 58 Polynitrotoluenes, 58 Porphyrins, germanium containing, photoirradiation, 137 Prenyl-1, 4-benzoquinones, 30 2-Propanoyl(N, N, 0)azoxybenzene, 235 Prop-2-enol, phenylation, 240 2-~Propyl-5-methyl- 1, 4-benzoquinone, photodimerisation, 23, 24 Pterocarpans, 18, 19 Pummerer reaction, 5, 6

Pyran-2-thione, reaction with nitrosobenzene, 66 Pyranylpyrazoles, 275 Pyrazines, synthesis from benzenediazonium salts, 252 Pyrazoles, synthesis from alkanal arylhydrazones, 278, 279 , from arylhydrazones, 274-284 , from benzenediazonium salts, 251 , from deoxybenzoins, 303 , from 2, 2-dicyanostyrene/Naryl-C-(phenylaminocarbonyl)formohydrazonoyl chlorides, 303 -, - from nitrilimines/alkynes, 303 Pyrazolidines, synthesis from arylhydrazones, 274-284 from benzenediazonium salts, 251 Pyrazolines, as scintillators, 282 -, synthesis from alkane-1, 3-dione bis(N-arylhydrazones), 281 , from arylhydrazones, 274-284 - , - from benzenediazonium salts, 251 - , - from nitrilimines/alkenes, 303 , from phenyl 3-(N,Ndimethylamino)propyl ketones, 282, 283 Pyrazolium cations, synthesis from 2, 3, 4-pentanetrione hydrazones, 277 Pyrazolones, synthesis from arylhydrazinylsulphonates, 281 Pyrazolo[3, 4-b]pyridines, synthesis from N-aryl-C-(chloroformyl)formohydrazonoyl chlorides, 303, 304 Pyridazines, synthesis from arylhydrazones, 287-289 (~2-Pyridine)tantalum complexes, 213 Pyridinium salts, reactions with aryIcopper-zinc complexes, 118 Pyridin-2-yl)pyrazolines, 282 Pyrido[1,2-c]benzo-v-triazinium tetrafluoroborates, synthesis from 2-(pyrid-2-yl)anilines, 253 Pyrimidiones, synthesis from arylisocyanates, 88 Pyrimido-1, 2, 4-triazines, synthesis from 5-phenylazo6-arylidenehydrazino- 1, 3dimethyluracils, 222, 223

366 Pyrrolidinotriazenes, lithiation and reactions with electrophiles, 329 -, Sandmeyer reactions, 329 Pyrrolidinotriazines, 327 1-(Pyrrolidin-l-yl)triazenes, 327 Pyrrolidones, synthesis from arylisocyanates, 88 Pyrrolo[3, 4-c]pyrazoles, synthesis from N-aryl-C-(chloroformyl)formohydrazonoyl chlorides, 305 Pyruvaldehyde oxime, phenylated by benzenediazonium chloride, 239 Quinhydrones, absorption spectra and crystalline state, 26 Quinoid, radical anions, 3 Quinolines, synthesis from phenylhydroxylamines, 69 Quinone azides, 53 Quinoxalines, 78 Radical cations, formation during arene nitration, 55 Ristocetin A, 161 Rubrene, metal complexes, 168 Ruthenocene, 165 Saligenins, dehydration, 37 Sandmeyer chlorodeamination reaction, 227 Sandmeyer reactions, 246, 330 Semidione-arylazo radical cations, rearrangement, 312 Semidione radicals, reaction with arenediazonium tetrafluoroborates, 311, 312 Semiquinones, formation from quinones, 3,6,7 Semmler-Wolff aromatisation, 74 Sigma complex, from 4nitrobenzenediazonium chloride/ N, N-dimethylaniline, 249 Silacyclopentanes, 131 Silapentanes, 131 Silatranes, reactions with mercury(II) chloride, 119, 120 Silyl ethers, ~-aryladon, 239 5-Spiro-cyclohexyl-2, 4-diphenyl-1, 2, 4triazolidine-3-thione, synthesis from

cyclohexanone phenylhydrazone, 297, 298 Spirodioxiranes, 52 Squaric acid, reaction with phenylhydrazine, 261, 262 Stannylcuprates, cross coupling with aryl triflates, 140 Starphenylene, chromium complexation, 187 Staudinger reaction, 92 Stilbene, 216 Styrene, arylation, 216 -, phenylation by phenylhydrazine, 260 (~-Styrene)chromiumtricarbonyl complexes, reactions with nitrile oxides, 209 Styrenes, arylation, 218 Terpenoids, functionalisations, 164 Tetraaryl-1, 3-butadien-1, 4-ylene dilithium, reactions with aryldihaloboranes, 125 Tetraarylleads, mass spectrometry, 145 Tetraarylstannanes, reactions with diborane, 142 Tetrachloro-1, 2-benzoquinone, 4, 5 Tetrachloro-1, 4-benzoquinone, triplet state reactions, 23 7, 7, 8, 8-Tetracyano-1, 4-benzoquinone, chemical reactions, 44, 45 7, 7, 8, 8-Tetracyano-1, 4-benzoquinone dimethide, 2 1, 4, 5, 8-Tetrahydroanthra-9, 10quinones, 14, 15 1, 2, 3, 4-Tetrahydro-1, 2, 4benzotriazines, synthesis from araldehyde 2-aminophenylhydrazones, 300, 301 1, 2, 3, 4-Tetrahydrocinnoline, 271, 272 cis-4b, 5, 9b, 10-Tetrahydro8, 9b-dimethyl-4b-(4methylphenylhydrazin-Nbyl)indeno[1, 2-b]indole, 271 1, 2, 3, 4-Tetrahydro 3-methoxy-3methyl-2-phenylbenzopyridazin4-one, synthesis from ohydroxyazobenzenes, 235 1, 2, 3, 4-Tetrahydro-7-methoxy-9methylpyrido[3, 4-a]indol-4-one, 273

367 2, 3, 4, 4a-Tetrahydro-2phenylcyclopentano(c)pyridazine, synthesis from 2-(2-chloroethyl)cyclopentanone, 288 1, 2, 3, 4-Tetrahydroquinoxaline, 271, 272 2, 3, 4, 6-Tetrahydro-1, 2, 4-triazino[5, 6c]cinnolin-3-one, 298 (~-Tetralin)chromiumtricarbonyl complex deprotonation-hydroxylation, 202 (776_Tetralol)chromiumtricarbonyl complexes, 188 (776-1-Tetralol)chromiumtricarbonyl complexes, 208, 209 1-Tetralones, 39, 51, 52 2, 2', 6, 6'-Tetramethylazobenzene, 233 2, 2', 6, 6'-Tetramethylazobenzene dioxide, 233 Tetramethyl-1, 4-benzoquinone, triplet state reactions, 23 2, 2', 4, 4'-Tetramethyl-4, 4'-biphenyl, 27 2, 2', 4, 4'-Tetramethyl-4, 4'diphenoquinone, 27 1, 1, 3, 3-Tetramethylindanone, photolysis, 41, 42 1, 1, 2, 2-Tetramethyl-5-(2, 3, 3trimethylbut-2-yl)indane, 244 2, 3, 4, 5-Tetranitrotoluene, synthesis from 4-methyl-2, 3, 5, 6tetranitroaniline, 58, 59 1, 1', 5, 5'-Tetraphenyl-3, 3'-biformazan, synthesis from 3-formyl-l, 5diphenylformazan/phenylhydrazine, 314 1, 1', 1, 5, 5'-Tetraphenyl-3, 3'-biverdazyl biradical, 314, 315 Tetraphenylcyclopentadienone oxime-Otosylate, aminating agent, 73 1, 3, 4, 6-Tetraphenyl-lH-1, 2, 4, 5tetraazahexane, isomerism with benzil bis(N-phenylhydrazone), 302 1, 2, 3, 4-Tetrazine-1, 3-oxides, synthesis from 1-(2-aminophenyl)3-'butyldiazene 1-oxides, 223 Tetrazole macrocycles, synthesis from arenediazonium chlorides/ malonodinitrile, 254, 255

Tetrazoles, synthesis from benzenediazonium salts, 253, 254 Tetrazolium salts, synthesis from benzenediazonium salts, 253, 254 Tetrazol-5-yl betaines, synthesis from biformazans, 314 Thiadiazines, synthesis from nitrilimines/potassium isothiocyanate, 304, 305 Thiadiazoles, synthesis from arylhydrazones, 285, 286 Thianthrene, radical perchlorate, 293 Thiatriazoles, synthesis from arylhydrazones, 286, 287 Thiazoles, synthesis from arylhydrazones, 285, 286 1,3-Thiazolidines, reaction with arenediazonium tetrafluoroborates, 327 Thiazolines, acetoxymercuration, 118, 119 Thiazol-2-ones, synthesis from N,Ndiphenylhydrazones, 286 Thienobenzoquinones, 45, 46 Thioarenes, synthesis from (~i6-arene)chromiumtricarbonyl complexes, 197 Thiophenoxybenzenerutheniumcyclopentadienyls, oxidation, 176 N-Thiosulfinylanilides, 92 Thorpe cyclisation, chloroimides, 291 Thymoquinone, photodimerisation, 23, 24 Toluene, nitration, 57 Tolueneironcyclopentadienyl cations, nitrosation, 179, 180 (~6-Toluene)molybdenumtricarbonyl complex, 212 Toluenerutheniumcyclopentadienyls, oxidation, 176 Toluenes, a-deprotonation, 178, 206-209 2-Toluidineironcyclopentadienyl cations, alkylation, 179, 180 Tolyllithium-iron-hydrides, 102, 103 Trialkylgermanium chlorides, reactions with alkali metals/aryl halides, 138 1, 3, 5-Triaminobenzene, synthesis from phloroglucinol trioxime, 78 1, 3, 5-Triamino-2, 4, 6-trinitrobenzene, 58

368 Triarylboridenes, stability, 123, 124 2, 3, 5-Triaryltetrazolium chlorides, synthesis from triarylformazans, 319 Triaryltin halides, reactions with diborane, 142, 143 Triazaphospholes, synthesis from aryl azides, 323, 324 Triazenes, synthesis from bromoanilines, 327, 328 1-[ 1, 2, 4-Triazine-(2H, 4H)-3, 5-dione5-yl]-2-[6-cyano-1, 2, 4-triazine-(4H)3, 5-dione-2-yl]benzene, 298 Triazoles, synthesis from arylhydrazones, 291-299 1,2, 4-Triazoles, synthesis from Narylbenzohydrazonoyl chlorides, 305, 306 , from N-benzyloxycarbonyl aaminoacids, 293 -, 1, 3, 5-trisubstituted, synthesis from N-alkylamide hydrazones, 295 Triazolinone, synthesis from diphenylnitrilimine, 308 Tributyltin radicals, bromine abstraction, 142 2, 4, 6-Trichlorophenylhydrazine, 257 Trifluoromethylbenzenes, nitration, 56 Trifluoromethylbenzoquinol, 50 a, ~, ;3-Trifluorostyrene, arylation and coupling with arenediazonium salts/ potassium thiocyanate, 242, 243 2, 2, 5-Trimethylcyclopentanone phenylhydrazone, attempted indolisation, 270, 271 2, 4, 6-Trimethylphenol, nitration, 56 Trimethylsilylazide, aminating agent, 73

Trimethylsilylbenzene, 128 Trimethylstannylimidazoles, fluorination, 144 1, 3, 5-Trinitrobenzene, synthesis from 1, 3-dinitrobenzene, 59 Tris(arylazo)diamines, synthesis from arenediazonium chlorides, 225 1, 3, 5-Tris(bromomethyl)benzene, reaction with tris(2-phenylthio)silane, 129 Tris(2, 4-dibromophenyl)amine, radical antimonyhexachloride, 293 Tris(2-nitrophenyl)triaziridines, 232, 233 Tris(2-phenylthio)silane, 129 2, 4, 6-Tris(trifluoromethyl)phenyllithium reaction with bismuth(III) chloride, 148 Ubiquinones, 6 a,~-Unsaturated esters, arylation, 218 o-Vanillyl alcohol, oxidation, 53 Vanomycin, 160 (~?6-Veratrole)manganesetricarbonyl tetrafluoroborate, 152 Veratroles, degradation, 29 Vicarious nucleophilic substitution, 62, 63 Wallach rearrangement, 235 Xanthone-1, 4-quinones, 9, 10 Xanthylium salts, 49 Zinin reduction, nitroarenes, 70