Advances in Physical Organic Chemistry, Volume 07

Advances in

Physical Organic Chemistry

This Page Intentionally Left Blank

Advances in

Physical Organic Chemistry Edited by

V. GOLD Department of Chemistry King’s College, University of London

VOLUME 7

1969

Academic Press, London and New York

ACADEMIC PRESS INC. (LONDON) LTD Berkeley Square House Berkeley Square, London, W1X 6BA

U.X. Edition published by ACADEMIC PRESS INC. 11 1 Fifth Avenue, New York, New York 10003

Copyright 0 1969 By Academic Press Inc. (London) Ltd.

All Rights Reserved

No part of this book may be reproduced in any form by photostat, microfilm, or any other means, without written permission from the publishers

Library of Congress Catalog Card Number: 62-22125

PRINTED I N OREAT BRITAIN BY SPOTTISWOODE, BALLANTYNE AND COMPANY LIMITED LONDON AND COLCHESTER

CONTRIBUTORS TO VOLUME 7 M. ANBAR,Exobiology Division, Ames Research Center, N A S A , Moffett Field, California 94035, U.S.A. D. BETHELL, Robert Robinson Laboratories, University of Liverpool, England. M. R. CRAMPTON,Department of Chemistry, The University, Durham, England.

V. GOLD,King’s College, University of London, Strand, London, W.C.2. England. Z. RAPPOPORT, Department of Organic Chemistry, The Hebrew University, Jerusalem, Israel.

V

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CONTENTS CONTRIBUTORS TO VOLUME 7

.

V

Nucleophilic Vinyl ic Substitution ZVI RAPPOPORT I. Scope . 11. Introduction . 111. The Addition-Elimination Route . A. Introduction . B. Element Effects and the Carbanionic Theory . C. The Stereochemistry of the Addition-Elimination Route D. Reactivity in the Addition-Elimination Route. . E. Substitution with Rearrangement (The “Abnormal” . Substitution) F. Summary . IV. The Elimination-Addition Routes . A. The cr,p-Elimination Route . B. The P,p-Elimination-AdditionRoute (The Carbenic Mechanism) . C. The &y-Elimination-Addition Route (The Allenic Mechanism) . V. The S,1 Route. VI. Substitutions Following Primary Rearrangements (The Prototropic Routes) . VII. Substitution via Two SN2Reactions . VIII. Substitution in the Presence of Metal Salts . Acknowledgments . References .

1 2 6 6 10 31 62 73 74 74 76 91 92 98 102 107 107 108 108

The Reactions of Hydrated Electrons with Organic Compounds M. ANBAR I. Reactions of Hydrated Electrons with Different Func117 tional Groups . vii

viii

CONTENTS

A. Saturated Hydrocarbons, Alcohols, Ethers and . Amines B. Alkenes . C. Carbonylic Compounds . D. Haloaliphatic Compounds . E. Other Electrophilic Functional Groups on Aliphatic Compounds . F. Aromatic Compounds . G. Heterocyclic Compounds . H. Organic Free Radicals . I. Concluding Remarks , 11. Radiobiological Implications of the Reactions of . Hydrated Electrons with Organic Compounds . A. Carbohydrates, Fatty Acids and Steroids B. Amino Acids and Peptides . C. Polypeptides and Proteins . D. Purines, Pyrimidines and Nucleic Acids . 111. Mechanism of the Reactions of Hydrated Electrons with Organic Compounds . A. The Energy of Activation of the Reactions of Hydrated Electrons . B. The Primary Products of eTq Reactions . C. The Mechanism of Electron Transfer . IV. Conclusion . References .

117 118 119 124 126 128 131 134 136 136 138 139 139 140 141 142 143 144 148 148

Structure and Mechanism in Carbene Chemistry D. BETHELL

I. Introduction . A. Definitions and Scope . B. Nomenclature and Pormalism . 11. The Structure of Carbenes . A. Theoretical Considerations . B. Direct Observation of Carbenes . 111. Carbenes as Transient Intermediates in Reactions in Solution . A. Criteria . B. The Decomposition of Diazoalkanes and Related Compounds .

153 163 157 157 157 160 169 169 170

ix

CONTENTS

C. Base-Induced a-Elimination D. Organometallic Reagents . IV. Mechanisms of Reaction of Carbenes in Solution A. Excitation, Multiplicity and Reactivity . B. Insertion . C. Addition to Olefins . D. Rearrangement . V. Conclusion . References .

177

.

184 187 187 190 194

200 202 202

Meisenheimer CornpI exes M. R. CRAMPTON

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I. Introduction A. Historical Aspects . B. Survey of the Reactions of Aromatic Nitro-Corn. pounds with Bases 11. Structural Studies of the Adducts . A. Adducts from Picryl Ethers B. Adducts from 1,3,5-Trinitrobenzene . C. Products from Picramides (2,4,6-Trinitroanilines) . D. Adducts from Other Substituted Trinitrobenzenes . E. Adducts from meta-Dinitrobenzenes . F. Adducts with Other Compounds . 111. Equilibrium and Kinetics Studies . A. Variation of Reactivity with Substrate Structure . B. Variation of Reactivity with the Attacking Nucleophile . C. Effects of Solvent on the Stabilities of the Adducts . References .

211 211 212

214 215 219 227

233 234 239 241 242

250 252 254

Protolytic Processes in H20-D20 Mixtures V. GOLD 259 I. Introduction . A. General Background . 269 263 B. List of Important Symbols . 11. “Simple” Equilibrium Theory for Reactions Involving 265 Aqueous Hydrogen Ions .

X

CONTENTS

A. Assumptions . B. Acid Dissociation as a Function of n . C. Extension of Simple Equilibrium Theory to Acid Catalysis . D. Acid Catalysis by Species other than H,O+ . 111. Solvent Isotope Effects in Relation to the Brmsted Catalysis Law . A. Acidity Constants of Hydrogen Ions . B. Application of the Catalysis Law . IV. Critique and Possible Improvements of Simple Theory . A. The Formula of the Hydrogen Ion and the Value of the Fractionation Parameter I . B. The Rule of the Geometric Mean . C. Absence of other Kinds of Solvent Isotope Effect . V. Applications of Theory to Experimental Results for Hydrogen Ions . A. Summary of Available Results for HzO-DzO Mixtures. B. Some Case Studies . VI. Catalysis by Species other than Hydrogen Ions in Aqueous Solution . A. Carboxylic Acids B. Hydroxide Ions . C. “Water-Catalysed” Reactions . VII. Solvents other than Water. A. Water-Dioxan Mixtures . B. Methanol . VIII. Speculative Generalities . References . AUTHOR INDEX. CUMULATIVEINDEX OF AUTEORS CUMULATIVE INDEX OF TITLES

. .

265 268 271 277 277 277 279 281 281 284 287 294 295 297 312 312 316 319 322 322 323 325 32 7 333 347 349

NUCLEOPHILIC VlNY LIC SUBSTITUTION ZVI RAPPOPORT

Department of Organic Chemistry, The Hebrew University, Jerusalem, Israel

. . . . . . . . . . . . . . . . .

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I. Scope 11. Introduction 111. The Addition-Elimination Route A. Introduction. B. Element Effects and the Carbanionic Theory C. The Stereochemistry of the Addition-Elimination Route D. Reactivity in the Addition-Elimination Route . E. Substitution with Rearrangement (The “Abnormal” Substitution) F. Summary IV. The Elimination-Addition Routes. A. The a,P-Elimination-AdditionRoute . B. The ,k?,B-Elimination-Addition Route (The Carbenic Mechanism) C. The B,y-Elimination-AdditionRoute (The Allenic Mechanism) V. The S,1 Route VI. Substitutions Following Primary Rearrangements (The Prototropic Routes) VII. Substitution via Two 4 2 ’ Reactions VIII. Substitutions in the Presence of Metal Salts References. .

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I.

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1 2 5 5 10 31 62 73 74 74 75 91 92 98 102 107 107 108

SCOPE

THISreview deals with the replacement of substituents in the vinylic position by anionic or neutral nucleophiles. Its division according to mechanistic routes suffers from the fact that for many systems there is a strong connection and mutual intercalation between several routes, but we will try to show the similarities in the behaviour of different systems and to discussthe various criteria which have been used for differentiation between the mechanistic pathways. Some topics, e.g. the stereochemistry and the element effect, are discussed in greater detail than others, especially when the data could be collected in convenient tables. No attempt has been made to cover all the synthetically used vinylic substitution reactions of which reviews are available, e.g. on /?-chlorovinyl ketones (Kochetkov, 1952, 1961 ;Kochetkov et al., 1961 ;Pohland and Benson, 1966), fluoro-olefins (Chambers and Mobbs, 1965) or tetracyanoethylene (Cairns et al., 1958; Cairns and McKusick, 1961). 1

2

ZVI RAPPOPORT

Nucleophilic vinylic substitution has previously been reviewed by de la Mare (1958), Patai and Rappoport (1964) and Rybinskaya (1967). While allylic SN2'reactions formally include a nucleophilic attack at the vinylic carbon atom, they are not discussed, except in cases when they have direct connection to the replacement of vinylic substituents.

11. INTRODUCTION Nucleophilic vinylic substitutions, owing to the inertness of simple vinyl halides, have the reputation of being difficult to conduct. Actually, a large number of these reactions are rather facile, provided that an activating group is attached at a vinylic position. The relative inertness of the unsubstituted vinyl halides compared to their saturated analogues is ascribed to the operation of the + M effect of the halogens (Hughes, 1938, 1941). The partial double-bond character of the carbon-halogen bond (equation 1) makes the bond cleavage more difficult. The importance of this factor increases with the degree of bond cleavage in the

transition state, i.e., it is large in SN1 reactions, but it is also expected to contribute to the lower reactivity in bimolecular, SN2-likereactions. Moreover, the sterically most natural approach of the electron-rich nucleophile to the carbon atom is the perpendicular direction where the higher concentration of Ir-electrons will decrease the reactivity by electrostatic repulsion (Catchpole et al., 1948). On the other hand, the transmission of electronic effects of electronattracting substituents which are bonded to the second vinylic carbon via the same rr-system, helps the nucleophilic attack. With strong - M substituents, e.g. cyano, a contributing dipolar structure carries the positive charge on the carbon atom to which the leaving group is attached (equation 2). For many common substituents the - M effect is much larger than the +M effect of the halogen, so that the overall reactivity of the vinylic system is frequently higher than that of the saturated analogue. q

I

L

-

7

NzC-CH=CH-CI

..

-9 n

+

N=C=CH-CH-Cl

~

(2)

While bond formation and bond cleavage are simultaneous in S N ~ reactions of saturated compounds, a vinylic carbon atom can become and remain four-covalent, bonded both to the nucleophile and to the leaving group. The initial difficulty in vinylic attack is therefore com-

NUCLEOPHILIC VINYLIC SUBSTITUTION

3

pensated for in two ways. The halogen leaves from a saturated centre and the negative charge on the neighbouring carbon supplies a driving force for the reaction, and the bond-breaking process may occur after the rate-determining step. The difficulty can also be avoided by attacking either a vinylic or an allylic hydrogen, both of which are more acidic than aliphatic ones, rather than the vinylic carbon. I n this case, the expulsion of the leaving group still occurs from the vinylic carbon, but the presence of a neighbouring negative charge helps in the carbon-halogen bond cleavage. Scheme 1, in which X is the leaving group, Y an activating group and Nu- is an anionic nucleophile, summarizes the routes which are discussed in detail in the following sections. I n line with the designations used previously (Patai and Rappoport, 1964)the carbon carrying the activating group is the a-carbon, and that carrying the leaving group is the @-carbonatom. I n the “addition-elimination ’’ routes, either via a carbanionic intermediate (I)or via a neutral adduct (11),the anionic nucleophile Nu- or the neutral nucleophile NuH attacks the @-carbonwith the expulsion of X. I n the a,@-route(IV), the p,p-route (VI) and the @, y“elimination-addition ” routes (VII), H X is eliminated in the initial step, and the nucleophile and hydrogen are then added to the intermediates. Substitution occurs also by heterolytic C-X bond cleavage in an SN1 process (X). Initial prototropy followed by substitution can also give vinylic substitution products (XII, XIV), as well as two consecutive SN2’ reactions (XV) where the leaving group leaves from an allylic position. Variations in the detailed behaviour of several of these routes result in the formation of rearranged products. The nucleophile could be attached to the a-carbon of the product via both the addition-elimination (111)and the elimination-addition (V) routes. Migration of the double bond, placing the nucleophile in the product either at a vinylic position (VIII, XI) or at an allylic one (IX, XIII) is also possible. Replacement of the halogen by a metal atom, and further reaction with an electrophile Ef (Curtin and Harris, 1951a, b; Curtin et al., 1955) also result in a formal vinylic substitution (XVI),but will not be discussed here. Nucleophilic vinylic substitutions are closely related to nucleophilic aromatic substitutions, as in both the leaving group leaves from an unsaturated carbon atom. However, the vinylic substitution routes are much more diverse, and disclose more of the details of the reaction. Stereochemical study of the reaction can give information on the lifetime of the intermediate and about the structure of the transition state

I. RiCX=CYRB

+Nu-

RlCNuX---CYRa

___f

1..

11.

-X-

-

____t

-HX

RICNuX-CHYR2 .txuli

111. RICX=CHY

A

IV. RICX=CHY

___t

-EX

RKXfX-CHNuY

-EX

R1-Y

V. VI. VII.

CHXdYR1

5

R'R*CHCX=CYR3

-EX __t

+NuH

:C=CYRl

--E

R'RZC=C=CYR3

VIII.

IX.

-X-

X. XI.

RlCX=CR2Rs

R'R2CH.CX=CYR3

+ RIC==CR2R3

+

-

+Nu-

_____f

+Nu-

+ R'R2kCX-CHYR3

RWNu=CYRa

Addition- elimination via an c,p-adduct.

RICH4NuY

Addition- elimination wiul rearrangement.

RXCNu=CHY

a,p-Elimination-addition.

R'CH=CNuY

or,p-Elimination-addition with rearrangement.

CHNu=CYR'

p,j3-Elimination-addition.

R'RWHCNu=CYRS

p,y-Elimination-addition.

R'R2CdNu-CHYR3

p,y:Elimination- addition with rearrangement.

RIR~CNU-CH=CYR~' p,y-,Elimination-addition with rearrangement. RlCNu=CRZR3

SNl reaction.

R I R ~ C ~ N U - C H Y R ~Substitution following initial prototropy.

4

--f

XIII. R*CX=CY-CHR2R3

--f

RlCHX-CY=CRZR3

+Nu+ RICHNU-CP=CR~R~

.1

XIV.

XVI.

Addition- elimination via "direct substitution".

R ' R ~ C H C X U ~ Y R ~Prototropy vinylic substitution + prototropy route

XII.

XV.

R'CNu=CYRa

RlCX=CRZRs

+Nu-

-

RlCX=CR2-CR3R4Y

-Y-

+Y-

R ~ C N U X - C R ~ = C R ~ R ~- xRiC=CRZR3

+E+

RlCNu=CY-CHR2R3

Prototropy --f allylic substitution + prototropy route.

RlCNu=CRLCR3R4Y

Substitution via two SN2' rearrangements.

R'OE=CRzR3 P

SCHEME 1

Allylic substitution following initial prototropy.

Gubstitution via vinylic carbanion.

NUCLEOPHILIC VINYLIC SUBSTITUTION

5

which is not available in aromatic systems. Several of the vinylic routes have no counterpart in the aromatic systems, while in the others the aliphatic intermediates, e.g. acetylenes, are much more stable than their aromatic counterparts, e.g. the arynes. The similarity between the two reaction categories is shown by the work of Beltrame et al. (1967b) on the reaction of 1,l-bis(p-nitropheny1)2-haloethylenes with ethoxide ion. The vinylic system is a vinylog of the nitrohalobenzenes which are usually studied in SNAr reactions. The activation parameters and the effect of substituents in the two systems were found to be comparable. 111. THEADDITION-ELIMINATION ROUTE

A. Introduction The addition-elimination route is the most studied one in Scheme 1. Since it involves a reaction of the nucleophile with the vinylic carbon atom, it is also the one which in actual fact is most correctly described as a “nucleophilic vinylic substitution”. We will therefore deal with it in the greatest detail. The direct attack at the vinylic carbon by the electron-rich nucleophile suggests that the reaction will be facilitated by diminishing the electron density at the double bond. This could be done by groups which are capable of spreading the negative charge, either by inductive or by resonance effects, and polarize the double bond in such a way that a partial positive charge is developed at the p-carbon atom. Since the contribution of structure (1) which aids the nucleophilic attack is dependent on such activation, the higher the charge-spreading ability of the group, the more facile will be the substitution via the additionelimination route. R1\ X

/y

,c=c p a‘R2

-

-

R\+ , y c-c

x’p

a\Ra (1)

A nucleophile with high carbon-basicity is necessary in this route, but if it is too basic, competition by elimination-addition routes will take place owing to attack on hydrogen rather than on carbon. Maioli and Modena (1959) had suggested that the attack of the nucleophile could take place by three closelyrelated variants of the same process (Scheme 2). I n the first one (i), the nucleophile Nu- attacks perpendicularly, and bond-breaking and bond-forming take place simultaneously. This was called the “direct substitution route”. I n the second one (ii),

6

Z V I RAPPOPORT

bond-breaking lags behind bond formation and the intermediate is a carbanion, which later eliminates the leaving group. The intermediate in the third route (iii) is the +addition product which forms the substitution product by elimination of the proton and the leaving group.

\ -*-

\

X’

I

‘R2

Nu-c-c X’

-/

‘R2

-A-

R1CNu=CYR2

SCHEME 2

Routes (i)and (ii)differ only in the life-time of the intermediate, although the “intermediate” of route (i) might only be a transition state. We will see that the stereochemistry of the product and the element effect can give information on this question. Most of the evidence points to a short-lived carbanionic intermediate, but in some examples an c@adduct seems essential. Since even the “direct substitution” is in itself an addition-elimination process involving the nucleophile and the leaving group, and since differentiation between the routes of Scheme 2 is not always possible, we will designate all routes of Scheme 2 as “additionelimination ”. The three routes are not always kinetically distinguishable. Silversmith and Smith (1958), for example, mentioned that the second-order with ethoxide kinetics in the reaction of l,l-diphenyl-2-fluoroethylene ion fits a reaction via a carbanionic intermediate, or the formation of a fluoroether, if the latter is either formed rapidly and decomposed slowly ( k , k , / ( k - , + k,)$ k4), or if it formed in a rate-determining step (klk,/(k-1 +k&k,). PhiCLCHF

+ EtO-

ki E-1

Sh&CH(OEt)F

.-

EtOH, En

k-’

PhzC=CHOEt

PhzCH-CH(0Et)F

Jf

+ EtO-

N U C L E O P H I L I C V I N Y L I C SUBSTITUTION

7

The stereochemistry of the substitution depends on the configuration of the substrates and on the specific route involved. A relationship between the configuration of the starting material and the product is expected for (i). The life-time of the carbanion formed in (ii) determines whether the reaction is stereospecific or gives the same cis-trans ratio from both cis and trans isomers by thermodynamic control. If an a,P-adduct is formed from an olefin possessing an a-hydrogen, the product configuration will be determined by the more stable transition state leading to elimination. With no a-hydrogen, both the cis and the trans isomers will give retention of configuration, provided that the two adducts from the two isomers do not interconvert, and that the addition and the elimination occur in the same fashion, e.g. trans. It will be shown that the substrate configuration is retained in the substitution product in most systems, and deviations usually indicate the intervention of other mechanisms. The interaction of strongly activated rr-acidic olefins with a basic nucleophile sometimes leads to the initial formation of charge-transfer complexes. Truce et al. (1965)mentioned that a mechanism involving an initial formation of charge-transfer complexes, such as ArS-(C12CACClJ and ArS-(Cl,C~C(Sh)Cl)-,is possible. Coloured complexes are formed in the reaction of tetracyanoethylene with primary and tertiary aromatic amines leading to N- and p-tricyanovinylation, respectively (McKusick et al., 1958). Tricyanovinyl chloride (Dickinson et al., 1960) and 1,2-dicarbethoxy-1,2-dicyanoethylene(Kudo, 1962) behave similarly. It was suggested that in the tricyanovinylation a a-complex (3)is formed from the .rr-complex of tetracyanoethylene and tricyanovinyl chloride (2) (Rappoport, 1963; Rappoport et al., 1964), and that an adduct (4) is formed from 1,a-dicarbethoxy-1,2-dicyanoethylene. Isotope effects suggested that (3) follows different decomposition routes to the final substitution products, depending on the leaving group (Scheme 3). Even if charge-transfer complexes may not be detected owing to their low equilibrium constants, it is attractive to assume that their formation plays an essential role in many vinylic substitutions. This would place the two reactants in favourable positions, and the complex may be a good precursor for a complete transfer of an electron pair. However, at present, this suggestion is only tentative and requires much more experimental support. Various mechanistic routes, such as addition, cyclization, etc., are available for the carbanions formed in the reactions of nucleophiles with activated o l e h s (Patai and Rappoport, 1962). Their competition with substitution can give information regarding the life-time of the ca,rbanionic intermediate. The retention of configuration of both isomers of

6

ZVI R A P P O P O R T

8

f

C(CN)Y=C(CN)X

(2) n-Complex

6

NRa I

C(CN)X-C(CN)Y

H

CX=C( CN)Y

(3) oLComplex

\.I

k?Y H

( X = Y = C02Et)

C(CN)=C(CN)Y

I

C(CN)X-I~(CN)Y (X = Y= Chi)

SCHEME 3

olefins having an a-hydrogen suggests that the expulsion of the leaving group is faster than the addition of a proton to the carbanion. On the other hand, formation of PhNH. CH=C(CN) .CH=CH. CN from the reaction of /3-chloroacrylonitrile with aniline (Scotti and Frazza, 1964) or of' (5) in the reaction of pyridine with perfluorocyclobutene (Pruett et al., 1952) may indicate the formation of long-lived intermediates.

NUCLEOPHILIC VINYLIC SUBSTITUTION

9

Internal cyclization to the oxirane (7) rather than to the substitution product (8) is found in the alkaline epoxidation of tetracyanoethylene (Linn et al., 1965). This may be due to a longer life-time of the intermediate ( 6 ) with the cyano leaving group, compared to carbanions with halide leaving groups. (NC)zC=C(CN)g

+ OOH-

\

4-

(NC)2C-C(CN)2

(NC)aC(OOH)-%W)a

‘d (7)

(NC)C(OOH)=C(CN)z (6)

(8)

From the many synthetic data (only a small part of which are included in this review) it can be seen that chlorine is displaced by a variety of nucleophiles which are more nucleophilic than the chloride ion, such as fluoride (Law et al., 1967), thiocyanate (Koremura and Tomita, 1962), arsenate (Backer and van Oosten, 1940), selenophenolate (Chierici and Montanari, 1956) or selenocyanide (Perrot and Berger, 1952) ions. Sulphinate anions, which displace the chlorine atom of fi-chlorovinylketones (Kochetkov et al., 1961), are themselves displaced by piperidine from 1,2-di-p-nitrophenylsulphonylethylene(Montanari, 1957). Trifluoromethylthiolate ion is displaced by methoxide ion (Harris, 1967), while the more basic methylthiolate ion is displaced by amines and carbanions (Gompper and Toepfl, 1962). While hydroxide ion and carbanions displace the cyano group (Webster, 1964), this group can be introduced at the vinylic position by displacement of the trialkylammonium group of RCO .CH=CHNR;Cl- (Nesmeyanov and Rybinskaya, 1957 ; Rybinskaya and Nesmeyanov, 1966). Carbanions (Cottis and Tieekelmann, 1961 ;Gelin and Makula, 1965) or amines (Claisen and Hasse, 1897; Kamlet, 1959) were found to displace alkoxide ions from the ethoxymethylene derivatives of active methylene compounds or from dicyanoketene acetals (Middleton and Englehardt, 1958) but the amino group of ( 9 )was displaced by hydroxide ion, probably owing to the special stabilization of the formed cyanomalonaldehyde anion (10) (Trofimenko,

10

Z V I RAPPOPORT

1963). The highly nucleophilic and basic carbanions derived from Grignard reagents (Schroll et al., 1965; Weintraub, 1966) or from active methylene compounds (Severinet al., 1964,1966)displace the substituted amino group of enamines. Somewhat unusual is the displacement of the azido group of ArCO .CH=CHN3 by either piperidine or methoxide ion (Nesmeyanovand Rybinskaya, 1962). The above examples demonstrate that a stronger nucleophile generally displaces a weaker one, although this is not always correct. The operation of the addition-elimination route and its details are inferred from the use of several criteria which will be discussed in the order below : (a) The element effect, i.e. comparison of the substitution rates of compounds which differ only in the leaving group, extended also to study of the competition of two leaving groups attached to the same or to different carbon atoms, of the same molecule. (b) The stereochemistry of the substitution. (c) The reactivity of various systems as a function of the structural parameters. The hydrogen-exchange criterion will be discussed in connection with the elimination-addition route.

B . Element Effects and the Carbanionic Theory 1. The element effect

One of the most powerful tools for finding out whether the leaving group participates in the rate-determining step of the reaction is comparison of rates with compounds differing only in the leaving group. Comparison of predictions regarding the relative reactivity of such compounds with the actual results can show whether the mechanism of substitution remains the same for the compared compounds, and if this is the case, what is the extent of bond-formation and bond-breaking in the rate-determining step. This “element effect ” was used in nucleophilic aromatic substitution (Bunnett et al., 1957 ; Bunnett, 1958) especially for halide ions as the leaving groups. I n the two-step additionelimination route, where a carbanionic intermediate is first formed by bond-making to the nucleophile and the product is then formed by rupture of the bond to the leaving group, the identification of the rate-determining step may be basedon this effect. The fluorine-carbon bond is much stronger than either the chlorine-carbon or the bromine-carbon bond. Hence, a mechanism which requires a considerable degree of halogencarbon bond stretching in the transition state (i.e. when bond-breaking is important) should show a slower reaction for the fluoro-olefin compared to the other halo-olefins. On the other hand, if the addition intermediate is formed in the rate determining step, the more polarized and the less hindered system will be the more reactive. Fluorine is the smallest and

NUCLEOPHILIC VINYLIC SUBSTITUTION

11

also the most electronegative among the halogens, so that both the electronic snd the steric factors would make the fluoro-olefin the most reactive in this route. On comparing bromo- and chloro-olefins it is assumed that the two halogen atoms polarize the double bond similarly, while the C-Br bond is expected to be broken faster than the C-C1 bond. The element effect is usually studied for the easily available chloroand bromo-olefins, but larger differences are expected on comparing them to the fluoro-olefin. Only two systems have been investigated in this respect. In the reaction of piperidine with PhCO.CMe=CHX (X = F, C1) at 30" in ethanol and in dimethylformamide the kF/kclvalues are 204 and 263, respectively (Beltrame et al., 1968). I n the reaction of 1,l-diphenylvinyl halide with ethoxide ion in ethanol, Ph&=CHX+EtO-

-+ PhzC=CHOEt +X-

(X=F, C1, Br)

the fluoride gave kz= 4.6 x M - ~ sec-' at 100" (Silversmith and Smith, 1958), while at 120' k2= 0-846 and 1.2 x M - ~sec-l for the chloride and bromide, respectively (Beltrame and Favini, 1963),giving kB,/kcl = 1.4. The extrapolated kF/kClvalue at 100" is 290, showing that this is a clear-cut case of rate-determining formation of an intermediate. 1,l-Diphenylvinyl ethyl ether was not always the sole product; 100, 91 and 400/, of it are formed when X = F , C1 and Br, respectively. Diphenylacetylene formed in an elimination-rearrangement process (p-RCeH4)2C=CHX+EtO-

4 P-RC~H~EC. CeH4R-P

accounts for the rest of the product. The above substitution rate constants were obtained by the dissection of the overall rate into two competing processes. Since the rearrangement is more pronounced when R is electron-donating, the evaluation of the element effect for the substitution is more difficult, but kBr/kC1 ratios of 2-3 were estimated for R = Me, Me0 (Beltrame and Carr&, 1961; Beltrame and Favini, 1963). When R = N 0 2 the substitution is the sole pathway and the ratios are 1.25-1.35 between 20-50" (Beltrame et al., 1967b). The k,,/k, ratios for the elimination-rearrangement process at 120" are 20,46 and 41 for R = H, Me and MeO, respectively. Bond-breaking is therefore important, and slow elimination of halide ion from vinyl carbanions, which are formed in pre-equilibrium, seems plausible (Jones and Damico, 1963). ,!?-Halopnitrostyrenes show ratios of 1-9-2.6 with PhS- (Marchese et al., 1968) while the ,!?-halocrotononitrilesgive ratios of 5-5-9 with the same nucleophile (Theron, 1967). There is other evidence that the latter reaction is an addition-elimination, and it is possible that bond-breaking plays a role in these substitutions.

12

Z V I RAPPOPORT

Since the bond cleavage is not important in the addition-elimination route, the element effect could be used for differentiation between it and the elimination-addition route, provided that a closely related model to the system studied is available. Such models for calibration of the (11)and the element effect for the u-arylsulphonyl-/3-haloethylenes a-arylsulphonyl-p-halopropenes(12)are the u-methyl analogues (13)for which the u,p-elimination-additionroute is impossible. Table 1 shows that for either cis- or trans-(13),the kB,/kclratiosarenear unity for highly ArSO&H=CHX (11)

ArSOZCH=CMeX

(12)

ArSO&(Me)=CHX

(13)

basic nucleophiles, such as MeO- and amines, and slightly higher with the PhS- ion. With PhS- and N;, which have relatively low hydrogen basicity and high carbon nucleophilicity, the kBr/kC1ratios for the eleven substituted derivatives from the series (11)and (12)are very similar, the values being 2.0-3.0. The higher element effects are shown by the cis isomers but the differences are small. With more basic nucleophiles, the element effects for (11)and (12)depend on substrate, nucleophile and configuration. The trans isomers, for which trans elimination of hydrogen halide is impossible, show kBr/kC1ratios of 0-74-1-13. These ratios are similar to those of (13)with the same nucleophiles, suggesting that the additionelimination route is the main and probably the only one for product formation. The values themselves show that C N u bond formation probably precedes the C-X bond breaking to a considerable extent. The kB,/kcl ratios for the cis isomers are very sensitive to the nature of the nucleophile, being 109-1 85 for MeO-, 18.3-38 for cyclohexylamine and 3.0-4-2 for di-n-butylamine with (ll),while derivatives of (12) show ratios over 200 for both amines. These element effects point to the intervention of an additional route, probably u,p-elimination-addition, which will be discussed in more detail in the following sections. While the p-methyl group seems to modify the kBr/kC1ratios, the effect is not mainly steric in origin, since the ratios are similar for the two amines which have different steric requirements. Caution should be exercised in using the element effect even when both compounds compared react via the same route. The higher reactivity of tricyanovinyl chloride (Dickinson et al., 1960) compared to that of tetracyanoethylene (McKusicket al., 1958) suggests a high element effect kCl/kCN. However, in the multistep reaction leading to the product, the leaving group participated in the rate determining step when X = CN, but not when X=Cl (Scheme 3) (Rappoport, 1963; Rappoport et al., 1964).

NUCLEOPHILIC VINYLIC SUBSTITUTION

13

TABLE1 Element Effect ( kBr/kcl) for the Reaction of cis and trans p-R1C6H&302CR2=CR3Hal Pairs with Various Nucleophiles at 0 ' in MeOH k€Ir/kCl

R1

R2

R3

p-NO2

Me

H

13

p-Me

H

H

11

185

0.84

H

H

H

11

144

0.84

p-NO2

H

Me

12

109

-

H

H

H

11

-

0.74

p-NOa

Me

H

13

1*4"

1.13'

p-NOa

H

H

11

38

1.01

p-Me

H

H

11

18.3

0.98

H

H

H

11

21

0.88

p-NO2

H

Me

12

213

-

p-NO2

Me

H

13

1.4'

0.74'

p-NO2

H

H

11

4.2

0.84

p-Me

H

H

11

3-5

1.08

H

H

H

11

3.0

1-03

p-NOS

H

Me

12

p-NO2

Me

H

13

2.6"

2.3"

p-Me

H

H

11

2.3

2.15

H

H

H

11

2.4

2.2

p-NO2

H

Me

12

2.4

p-NOa

H

H

11

3.0"

2.0"

pMe

H

H

11

2.6"

2-10

H

H

H

11

2-15"

2.0"

Nucleophile MeO-

n-Bu2NH

PhS-

At 25'.

Series

cis

trans

Reference

0.93"

0.85'

Maioli et al., 1960 Campagni et al., 1960 Campagni et al., 1960 Modena et al., 1960 Campagni et aE., 1960 Maioli et al., 1960 Campagni et al., 1960 Campagni et aE., 1960 Campapi et al., 1960 Modens, et al., 1960 Maioli et al., 1960 Campagni et al., 1900 Campagni et al., 1960 Campagni et al., 1960 Modem et al., I960 Maioli et al., 1960 Campagni et al., 1960 Campagni et al., 1960 Modem et al., 1960 Campagni et al., 1960 Campagni et al., 1960 Campagni et al., 1960

233

-

-

14

Z V I RAPPOPORT

2. The “geminate” element effect (both leaving groups on the same carbon atom) The presence of two different leaving groups at the double bond, either on the same carbon or one on each of the two carbon atoms, gives rise to other types of element effects. When the two groups X and Y are attached to the same carbon atom, the two transition states do not lead to the same product, as was the case with the element effect just discussed, but to two different products. The two transition states differ not only in the leaving group but also in the p-group which stabilizes them: Y stabilizes the transition state leading to the expulsion of X, while X stabilizes the transition state leading to the expulsion of Y. h,-xR1R2C=CNuY

+

R~R~C=CXY N ~ -

__+

R~R~C-CN~XY

-€ h,-Y-

R’R2C=CNuX

This element effect will be called the “geminate element effect”k l / k 2 , and it is related to the ratio of the substitution rates of R1R2C=CX2and R1R2C=CY2 by Nu- in the following way:

ki/kz = [(ki/k4)/(k2/k3)1 X kdk3 where k3 and k4 are the rate constants for the processes defined below : R1R2C=CX2+NuR1R2C=CY2+Nu-

-% R1R2C=CNuX -% R1R2C=CNuY

The ratio k l / k 4is therefore the element effect k,/ky of the preceding section for the pair R1R2C=CXY and R1R2C=CY2, and k 2 / k 3 is k y / k x for the pair R1R2C=CXY and R1R2C=CX2. For good carbon nucleophiles, the value in parentheses is expected to be close to unity, as discussed above, i.e. k l / k 2 k4/k3. Owing to lack of experimental data this analysis has not yet been applied. It would be of interest to compare, for example, the substitution rates of R1R2C=CC12and R1R2C=CF2 and to evaluate in what cases chloride would leave preferentially to fluoride from R1R2C=CFC1 systems. From Table 2, which contains the results for several systems for which the geminate element effect is possible, it seems that the competition between two leaving groups results, in most cases, in expulsion of the less basic one. Thus, the highly basic amino or alkylamino groups always remain attached to the double bond while the bonds to the less basic met hylthio , t rifluoromet hylthio , cyano, fluoro, chloro or ethoxy groups are cleaved. However, the amino group is expelled in preference N

TABLE 2

Leaving Groups in Intramolecular Competition System

Nucleophile

Leaving group

Product

Reference Josey, 1964

N&- or NH3

CH(CN)~ MeOzC. C(CN)=C(SMe)NHPh (NC) 2C&( CN)NHBu (NC)zC--C(OR)NHz (NC)zC==C(CN)OEt (NC)zC=C( CN)Cl

m 3

(NC)zC=C(NHZ)Cl CF3COCl=C(NMePh)cl (CFaS)zC=C(SCF3)NEt2 (CF3S)zC=C( SCF3)OMe ROzSC(CN)=C(CN)SOzR (NC)CCI=C(CN)Cl

EtOH PhNHMe FMeORNHz F-

MezNH NHRlRZ CaH5NMez CsH5NMez

NH3 MeSCNROEtOc1-

[CFaC(C(CN)z)zIMeO2C. C(CN)=C(NHz)NHPh (NC)2C==C(NMez)NHBu (NC)zC==C(NH2)NR'R2 p-Me2N. C6H4. C(CN)=C(CNz)a p-MezN .C&C(CN)=C(CN)2

c1-

(NC)zC==C(OEt)NH2 CF3. CO. CCl=C(NMePh)Z (CF3S)zC----C(NEtz)F (CFsS)zC=C(0Me)z (NC)C(NHR)=C(CN)SOzR ( N C ) C C l 4 ( C N ) F+ (NC)CF=C(CN)F (NC)aC=C(CN)z (NC)zC=C(CN)Cl CFs CCl=CF2 CF3. CCl=C(SC4Hg-n)F CF3. CCI==C(SC&b-n)Cl EtOzC. C(CN)=C(NHAr)COzEt EtOzC .C(CN)=C(NHAr)CN CHClF .CO N E t z CHClF.CO.NEtz CFz=CFRe( C0)s CFz=CFFe(CO)z-n-CsH5 PhCF=CPhCl EtOCF=CPhCl

clFPSF3CSRSO, c1-

CN-

c1-

CF3. CCl-CC1F CF3. CCl=CClF

Fn-C4HgS-

c1c1-

EtOzC .C(CN)=C(CN)COzEt

h

CFZ=CFNEtz CCLF=CFNEtz CFZ=CFCl PhCF=CFCl EtOCF=CFCl a

Fm

2

OHOHRe(C0); Fe(CO)z-n-CsH; PhLi PhLi

CNCOzEta F-

Fc1c1F-

F-

Formed via the intermediate (NC)zC=C(CF3)NHNHz.

+

.

+

.

* See text.

Josey, 1964 Gompper and Toepfl, 1962 McKusick et al., 1958 Martin et al., 1966 Dickinson et aZ., 1960 Dickinson et al., 1960; Rappoport et al., 1964 Middleton et aZ., 1958 Scherer et al., 1966 Harris, 1967 Harris, 1967 Martin, 1963 Rohm and Haas, 1962 DuPont, 1961 Miller et al., 1960 Thompson, 1955 Kudo, 1962b Kudo, 1962b Yakubovich et al., 1966 Yakubovich et al., 1966 Jolley and Stone, 1965 Jolley and Stone, 1965 Meier and Bohler, 1957a Meier and Bohler, 1957b

ZVI R A P P O P O R T

16

to the very basic trifluoromethyl group. Chloride and sulphinate ions are found to be better leaving groups than cyanide ion. Deviation from this generalization is found in the reaction of tricyanovinyl ethyl ether with N,N-dimethylaniline, in which the ethoxy rather than the less basic cyano group is substituted. This discrepancy may result from a difference in the details of the substitution mechanism for this ether compared to the other compounds of Table 2. The validity of a scale of leaving aptitude based on the geminate element effect should be tested by comparing closely-related leaving groups, such as the halogens, rather than by comparing widely different groups, e.g. amines with halogens. If basicity is the main factor, chloride ion should always be a better leaving group than fluoride ion. The data of Table 2 do not support this conclusion. With fluoride ion or with the transition metal carbonyl ions, chloride competes favourably with fluoride, while fluoride leaves preferentially on reaction with phenyllithium. Substitution products of both fluoride and chloride are formed with butylthiolate ion. The available data are too limited for generalisation regarding the dependence of the geminate element effect on the nucleophile. It is predicted that in an acidic medium a protonated amino group will leave preferentially to many other groups. While this geminate element effect has not been investigated in such media, it is known that the salts of /?-alkylammoniumvinyl ketones are better ketovinylation reagents than 8-chlorovinyl ketones (Nesmeyanov and Rybinskaya, 1957). Reaction of 1,2-dicarbethoxy-l,2-dicyanoethylene with p-substituted anilines gave the product of substitution of either the cyano (14) or of the carbethoxy group (15). When the olefinlamine ratio was 1:2, (14) predominated, while (15) predominated when the ratio was 2 : 1 (Kudo, 1962b). Tertiary aromatic amines gave (16), where only the cyano group was lost (Kudo, 1962a). Formation of (15) is interesting since carbethoxy is a very unusual leaving group, and the amount of the nucleophile does not usually change the geminate element effect. Formation of &,/?-adduct (17) of t’heamine and the reactive olefin, may explain the C0,Et eliminaNC\

NC,.

COzEt

,c=c’ EtO&

,C02Et

,c=c EtOzC

\

t HCN NHAr

f ArNH2

\CN

NHAr

,c=c \CN

EtOzC (15)

+

HC02Et

NUCLEOPHILIC VINYLIC SUBSTITUTION

17

tion. A similar intermediate (4) was obtained from reaction at the p-position of aromatic amines. p-RzNCsH4C(COzEt)=C(CN)COzEt (16)

ArNHC(CN)(COzEt)-CH(CN)COzEt (17)

I n the presence of amine, (17) may eliminate HCN or HC0,Et. An amine-induced elimination of HCOzEtis depicted in (18) and is possibly favoured by formation of hydrogen bonds of the carbonyl oxygen with the amino hydrogen, and of the amino nitrogen with the a-hydrogen. However, it does not explain the dependence of the (17)/(15)ratio on the amine and, if formation of (18) is quantitative, it even contradicts it. NC,

,NHAr C-

/CN

3. The “vicinal ” element effect (the leaving groups on neighbouring

carbons);Park’s carbanionic theory An additional type of element effect, which will be called the “vicinal element effect’’ is possible when two leaving groups are attached at both ends of the same double bond. Whether X or Y leaves earlier, or which one leaves alone when only monosubstitution occurs, depends on the preferred position of the attack of the nucleophile, and on the reversibility of this step. For irreversible attack, the (19)/(20) ratio would be determined by the relative electrophilicity of the a- and the p-carbon

atoms, which is determined by the activating ability of both a- and 8-substituents. For reversible attack, the ratio would be determined by the relative carbon basicity of the nucleophiles for the two carbon atoms, and by the relative leaving ability of X and Y. The presence of a strong activating u-group always controls the substitution course, e.g. compound (21) loses only the chlorine to the carbonyl group (McBee et al., 1962b)while (22) loses the vinylic chlorine atom rather than fluorine (Scherer et al., 1966).

18

ZVI RAPPOPORT

The vicinal element effect was studied recently in cyclic polyhalogenated Olefin8, especially by Park and coworkers. While for these compounds only addition-elimination operates, the allylic halogens may be the ones replaced in competition with the vinylic ones (see below). Extensive work has been done on the reaction of substituted halocyclobutenes with EtO- ions in ethanol. Conformational complications possible in the alicyclic systems are small, and the effect of a-and P-substituents to the negative charge of the intermediate carbanion could be separated (Park et al., 1965). When X = Y attack at either position would give carbanions which are equally stabilized by the a-group, and the products would be determined by stabilization of the carbanion by groups 8- to the negative charge. When the j3-groups are equal, and X and Y are different, the a-stabilization could be evaluated. The results of Park’s group on the ethoxide ion reactions have been summarized by the following empirical rules (Park et al., 1966) which will be referred to as “Park’s carbanionic theory”. The main assumption is that, even when the double bond is substituted by the mildly electronattracting halogens, the substitution intermediate is a carbanion. The nucleophilic attack is assumed to give always the carbanion best stabilized by substituents in the a-position to the negative charge. In the terminology of this theory “a-” and “j3-stabilization” relate to the negative charge, i.e. in (23)Y is an a-stabilizing group and X, Nu, RS and R4 are /3-stabilizing groups. The NMR evidence shows that the electron-attracting ability of the halogens increases with their size, R ‘ R Z ~ ~ ; ~

+-Nu-

__f

@a

NU

(23)

NUCLEOPHILIC VINYLIC SUBSTITUTION

19

probably since the spreading of the negative charge over a large atomic volume more than compensates for the lower electronegativity of the heavier halogen. Therefore, a larger halogen atom is expected to stabilize the negative charge better than a smaller one, and from studies by Hine et al. on the haloform ions, the expected order of a-stabilization is : I > Br > C1 >F > CF, > EtO. If the attack on the two carbons involved gives two carbanions which are equally stabilized by a-substituents, the one having the better t9stabilizing groups would be formed preferentially or, if steric effects are important, the one with the lower steric interactions. Increase of the a-stabilization would reduce the importance of /3-stabilization. An important assumed property of the intermediate carbanion is that its further reactions are independent of its way of formation, and the leaving group may be the one which was either allylic or vinylic in the original olefin. The less basic 8-leaving group would be eliminated preferentially, probably in the order I- > Br- > C1- > F- RO- > H-. Fluoride ion would not leave from a CF2group when another potential leaving halogen is available. Finally, for two identical potential 8-leaving groups, the one forming the most stable olefin would be eliminated. The formation of both vinylic and allylic products could also be explained in terms of competing vinylic SN2 and SN2' substitutions. Since the carbanionic theory is simpler, and it also accounts for the formation of saturated ethers in weakly basic conditions, it seems preferable to a combination of mechanisms, and the examples below are discussed according to it. Reaction of ethoxide ion with 1,2-dichlorotetrafluorocyclobutene (24) gives both the monoether (26) and the triether (30) (Park et al., 1951).

=-

20

ZVI RAPPOPORT

The initially formed carbanion is (25),from which preferential replacement of chloride over that of fluoride ion gives (26). Further attack could give (27),which is stabilized by a-chlorine, rather than (31),which is stabilized by an a-ethoxy group, and (28)is expected to be formed by the loss of the less basic fluoride. Further attack on (28)would give (29), which is stabilized by a-chlorine, preferentially to (32),which is stabilized by a-fluorine, and the loss of fluoride rather than ethoxide ion will give the triether (30). Since this ether is the final product of the reaction FZ EtO

of (24)with ethoxide ion, and it could also be formed by one vinylic substitution and two SN2 allylic reactions without rearrangement, the formation of the rearranged triether (33)from the reaction of the monoether (26)with methoxide ion (Park et al., 1963a)fit the predictions of the

M:q:Et MeO-

C1-

OEt

OMe

(33)

carbanionic theory. A similar reaction gives analogous results with 1,2-dichlorohexafluorocyclopentene and alkoxide ions (Dreier et al., 1964) where the dimethoxy-ether (34) was also isolated (McBee et al., 1962a). F

The effect of j3-substituents (Park et al., 1965) is demonstrated by the reactions of 1,2,3-trichlorotrifluorocyclobutene (35) with sodium ethoxide. While stabilization by a-chlorineis commonto both carbanions (36and 37)formed by attack at the two vinylic positions, (36)is stabilized by j3-chlorineand ,!?-fluorine,and (37)by two jl-fluorine atoms. Assuming

NUCLEOPHILIC V I N Y L I C SUBSTITUTION

21

that the relative stabilization at the /?-positionis similar to that of the a-position, i.e. is higher with the larger halogen, (36) should be more stable. Indeed, the substitution products (38 and 39) formed from (36) and (37), respectively, are formed in the ratio 61 :39, which is in agreement with this assumption.

(35)

I

I

a-Stabilization of bromine exceeds that of chlorine as judged by the 1:3 ratio of the monoethers (41) and (42) from the reaction of l-bromo-2chlorotetrafluorocyclobutene (40) with EtO- ion.

:I@:

EtO-b

"'uFzF2nFz C1-

OEt

(4)

+

EtO

(411

-Br

(42)

It is expected that by substitution of (43) which has a-groups similar to those of (40), and/?-groupssimilar to those of (35), both the carbanions F z q F C l

OEt

Br-

c1 (43)

+

Fzp;:

EtO Br

(44)

(45)

1

1

22

ZVI RAPPOPORT

(44) and (45) will be formed. While a-stabilization will favour (44) over (45) by a ratio of 3 :1, the /I-stabilization of (45) will exceed that of (44) by a ratio of 61 :39. If the effects of a- and /I-substituents are additive, a 57 :43 ratio of (46) to (47) is expected by combination of the above ratios. The formation of the monoethers in a ratio of 68:42 (and less accurately in other systems) confirms this additivity. The effect of y-groups may sometimes be important, ifthey are able to participate in the spreading of the negative charge. The formation of (51) rather than (48) from the reaction of MeO- ion with (49), probably reflects such stabilization via the intermediate ion (50) (McBee et al. 1962a).

C ! l h C l

c1

\ I OMs (48)

C;l-2l (0Me)z

(OM42 +

MeO-+

(49)

A steric alternative to the carbanionic theory would assume that the less hindered position is always being attacked. The formation of (44) with the higher steric interactions may be an argument for the operation of electronic rather than steric effects. Another example is the exclusive formation of the ether (53) from the reaction of (52) with ethoxide ion (Park et al., 1967a). This is in line with the expected higher stabilization by a /3-CF2group compared to a /3-CH2group but, owing to the small size of the fluorine atom, both (53) and its isomer (54) should be formed if the reaction is governed by steric control. It should be mentioned, however,

that for nearly equal steric effects, the electronic ones are expected to take over. I n the systems described above, only two products were formed owing to the preference of halogen to leave the C(0Et)Hal group rather than

NUCLEOPHILIC VINYLIC SUBSTITUTION

23

the CFHal group. However, in less favourable cases two vinylic and two allylic substitution products may be formed. 3,3-Difluoro-1,2,4,4tetrachlorocyclobutene (55) gives primarily the two vinylic substitution products (58) and (60) and an allylic one (59), via the carbanions (56) and (57) which are formed in a,ratio 89: 11. This high ratio reflects the

higher stabilization of 8-chlorine atoms over 8-fluorine atoms, while the formation of more (59) than (58) shows that the chlorine in the CCI, group is a better leaving group than that in the C(0Et)Cl group. With the already evaluated higher stabilization of u-bromine over a-chlorine ((40)+ (41)+ (42)) and on the assumption of additivity it could be predicted that (61) would give a 57:43 ratio of (62) to (63).

E;p;

F'c]"'

+

Br -C1

q c 1 2 OEt c1

Br (61)

(62)

(63)

/ 7 Fznc12 .

.

Br

-OEt 34%

(59) 4%

2

(65)

TABLE 3

TRT-

Subst,itution in Halocyclobutenes

RIR2

X

+NU-

RZZn R 3 ; '

+Nu-

~

R

l

R

D

C

NU

R : q R Y

RilqR:'

R'R'p;

X

Y

R1,RZ

R3,R4

Nucleophile

c1 C1 Br c1 Cl Cl

c1

H

C1 C1 c1

c1 Br H c1

F,F F,F F,F F,F F,F F,F F,F F,C1 F,C1 F,F

F,F F,F F,F F,F F,F F,F F, Cl F,F F,F C1,Cl

EtOEtOEtOEtOMeOEtOEtOEtOEtOEtO-

C1 C1

EtO

C1,Cl F,F

F,F C1,Cl

EtOEtO-

a

Br

Substitutionproduct

V

v+v v+v v+v

A A

v+v v+v A V+A+V V A

Y

NU

NU

NU

EtO

R k R ' p R 4

X

X

Br I I

"'"' 9

NU

yoI

yo 11

1OOb 25 10 2.5 100

75 90 97.5

100 39 42 100 11 34

61 58 89 66 100

Leaving group from (I) C ( 0 E t )* * .C1 C(OEt).--Br CI.--Br CI..-Cl C F * . .F CF. * .F C ( O E t ) - . -C1 C(OEt)---Br C F . . .C1 C ( 0 E t ) . * *C1 C(OEt)...Br

Leaving group from (11)

CBr---I CCl. * -1 C ( 0 E t ) - . *C1 C ( 0 E t ) . * .C1

Nu

Reference Park et al., 1951 Park et al., 1965 Park et al., 1968 Park et al., 1968 Park et al., 1963a Park et al., 1963b Park et al., 1965 Park et al., 1965 Park et al., 1963b Park et al., 1965

CC1- . .C1+ C ( 0 E t ) . . .C1 C ( O E t ) - . .C1 Park et al., 1965 CCl.. .c1 Park et al., 1965

C1

c1 EtO c1 c1 F

c1 c1

C1 F

H

c1

C1

c1

c1 C1 c1

a

F C1

F, F

EtO-

C1. E t O C1, E t O F. F EtO, E t O MeO, E t O F, F F, F F, F H, E t O

EtOEtOEtOEtOMeOEtOEtOEtOEtO-

I F

A

v+v A V V V V V V V

100 29

71 100

lo@ 47

53 100 100 100

CCI.. .c1 C(OEt)..*CI C(OEt).*-Cl C ( 0 E t ) . * *C1

C(OEt)...CI C(OEt)...Cl C ( 0 E t ) . . *C1 C(OMe).-.F C(0Me). . .F C ( O E t ) - . .C1

C(OEt)..*F

100 100

C(OEt)** * F

100

C(0Me). . .F

BH,

100

CH.. .F

Piperidine

100

C(N<)-..F

Morpholine

100

C(N<). . .F

Park et al., 1966 Park et al., 1965 P a r k et al.,1965 Park et al., 1966 Park et al., 1965 P a r k et nl., 1963a Park et al., 1966 P a r k et al., 1967a Park et al., 1967a Park et al., 1963b

Park and Frank, 1967 Park and Frank, 1967 Park and Frank, 1967 Park and Frank, 1967

2

c:

cz m

FQFz

F,F

H,H

BH,

100

V

Park a n d Frank, 1967

c: W

m

I3 H

H

I3

9

20 V

c1

OMe c1

F,F

F,F

Me3MH (M = Si, Ge)

V

100

100

C(OMe).--F

CMMe3. * Cl

Park a n d Frank, 1967

Cullen and Styan, 1966

2

TABLE 3-continued Substitution" product

%I

Leaving group from (I)

Leaving group from (11)

X

Y

R1,RZ

R3,R4

Nucleophile

Br C1

F EtO

F,F F,F

F,F F,F

EtMgBr EtMgBr

V V+A

100 100

C1 C1

Et MegAs

F,F F,F

F,F F,F

EtMgBr MezAsH

V+A V

25

75 100

C1

H

F,F

F,F

LL4lH.I

V+A

63

37

CF.0.F

CH. * .C1

NaBH4

V+A

16

84

CF-.*F

CH- . .C1

% I1

CEt . . .F C(OEt)*..C1+ CF. * * F CEt**.Cl

Reference Sullivan el al., 1964 Sullivan et al., 1964

CF- . .F Sullivan et al., 1964 C(AsMe2).. .C1 W e n and Dhaliwal, 1967

MeS BUS F

F F MezAs

F,F F,F F,F

F,F F,F F,F

MeSBuSMezAsH

V V V

100 100 100

C(MeS). . *F C(BuS)* * F C(MezAs).. .F

F

PhzP

F,F

F,F

PhzPH

V

100

C(Ph2P). * . F

F

F

F,F

F,F

Nuc

V

100

CN. *F

.

Burton and Johnson, 1966 Burton and Johnson, 1966 Cullen et al., 1967 Pruett el al., 1950 W e n and Dhaliwal, 1967 W e n and Dhaliwal, 1967 c

A=Allylic product; V=Vinylic product. I=II. oNu-=Et2PH(CullenetaZ., 1967);BuS- (Pruett et al., 1950); MeS- (Cullen etal., 1967); PhaPH (Cullen and Dhaliwal, 1967); MezAsH (Cullen andDhaliwal, 1967); Mo(CO),, Re(C0); (Jolley and Stone, 1965); P(0Et)a (Knunyants et al., 1964); MeClzSiH, MesSnH (Cullen and Styan, 1966); MeO- (Parket al., 1949).

NKJCLEOPHILIC V I N Y L I C S U B S T I T U T I O N

27

The actual ratio found is 66: 34, i.e. the stabilization by two 8-chlorine atoms exceeds that calculated from the reaction of (55) (Parket d., 1965). Similar reactions of substituted cyclobutenes are collected in Table 3, which lists the attacked system, the nucleophile and the leaving group, and the ratio of allylic to vinylic products. The following order of leaving ability of 8-substituents is obtained from the Table :

The broken line shows the bond cleaved. Ring size has little effect on the ratio of the two vinylic haloethers formed in the reaction of 1,2-dihaloperfluorocycloalkeneswith ethoxide ion. The ratios of the ether carrying the heavier halogen to the second one are 3, 9 and 39 for the (Cl, Br), (Br, I)and (Cl, I)substituted pairs in 1,2-dihalohexafluorocyclobutenesand 3.3, 8.1 and 32 for the 1,a-dihaloheptafluorocyclopentenes (Park et ul., 1968). This a-stabilization is the same one as found from exchange experiments of the haloforms hydrogen (Hine et ul., 1967; Slaugh and Bergman, 1961). While secondary amines give usually the same type of substitution products as alkoxides, the vinylic substitution product with primary amines is capable of prototropy. Further attack by the amine results in the formation of the iminoamines such as (66) (McBee et al., 1965). does However, 1-chloro-2-dimethylarsino-3,3,4,4-tetrafluorocyclobutene

F u N H M e

not give a trisubstituted product with dimethylarsine, but the divinylic derivative (67) (Cullen and Dhaliwal, 1967) showing that the behaviour of this large nucleophile is inconsistent with either steric or electronic control of the reaction. The carbanionic theory does not fit all types of nucleophiles, as shown by Burton and Johnson's work (1966), on substitutions with complex

28

ZVI RAPPOPORT

metal hydrides. While both LiAlH, and NaBH, replace the vinylic fluorine of (68, n = 2,3), the analogous compounds with vinylic chlorine (70, n = 2,3) give bothvinylic (69) and allylic products (71). The (71)/(69) ratios are 11 and 5 for LiAlH, and NaBH4 for n = 3, and 1.7 and 0-2 respectively for n= 2.

H- - r

L 168)

F

+

MH4-

Hr l € i

Hzr(r:-i (69)

+ MH4-

H

___f

+ (69)

__f

c1 -

The carbanionic theory predicts that (71) should be the main or the exclusive product. This is found with (70, n = 3) as well as in the reaction of LiAlH, with (72) which gives only (73) (Feast et al., 1966). Formation

of (73) requires that the higher stabilization by an a-Cl over that of a-F is more than compensated by the higher stabilization of the P-CF2 and P-ClH compared to P-CH2and P-CFH groups. The results for the four-membered ring are different. The strong dependence of the (71)/(69) ratios on the size of the reacting hydride suggests the operation of steric control for bulky nucleophiles, where the larger nucleophile is more selective, attacking the less hindered position. The results are even more complex with Grignard reagents. Exchange reactions, forming e.g. (74), are sometimes the main ones, but l-bromopentafluorocyclobutene gives (75) with EtMgBr, as expected according to the carbanionic theory. While all the five substitution products of (76) with EtMgBr (Sullivan et al., 1964) could be accounted for by the theory and the reasonable leaving-group order C.HEt > “OEt

c..

‘Et

29

NUCLEOPHILIC VINYLIC SUBSTITUTION

the explanation also demands that a-C1 and two P-Et groups stabilize less than a-Et, P-Et and 13-Cl, contrary to the theory. Moreover, the

F

+

YZI_IFZ

EtMgBr

F

F 2 n b3;

-

Et

MgBr

(75)

(74)

EtO

1%)

dependence on ring size is similar to that found for the metal hydrides. While EtMgBr gave exclusively the disubstituted vinylic products (78) when reacting with perfluorocyclobutenes and pentenes (77, X = F, n = 2,3), the dichloroperfluoro compounds (77, X = C1) gave both (78) and the rearranged (79)with (78)/(79)ratios of 4.6 and 1.5 for n = 2 and n = 3 , respectively (Park et aE., 1967b). Two possible sources for the

n-

r ( C F d n 1 Et

EtMgBr

X

+

r

z

E

h

Et

X

(77)

-

1

F (79)

(78)

difference from alkoxides might be the differences in the solvents used (ethers vs. alcohols) and in the bulkiness of the Grignard reagents. Moreover, reactions with hydrides and Grignard reagents should be subject to kinetic control owing to their irreversibility, and the different course with ethoxide ion might reflect reversibility with the less basic nucleophile. The carbanionic theory is inadequate for systems with vinylic fluorines. Both vinylic fluorines are replaced in polyfluorocyclobutene (Park et al., 1949) (Table 3) while 1,2-dichlorotetrafluorocyclobutene(24) gives the triether (30). The differences were ascribed to higher reactivity of the vinylic fluorine compared to the chlorine, as a result of the steric and the electronic factors already discussed (Stockel et al., 1964, 1965). Both chlorines of (24) are replaced if an activating group is introduced in the first substitution step, as in the formation of (80) (Frank, 1965). (RO)sP

c1n

C

1

-

(RO)z(O)PJ ( C F I I p ( 0 ) ( O H ) . (80)

30

ZVI RAPPOPORT

The degree of preference of elimination of the vinylic fluorine (Park et al., 1968) depends on the ring size. No rearranged product is formed with perfluorocyclobutene,4% allylic product is formed in the methoxide ion-perfluorocyclopentene reaction, and 15-3 1% of the rearranged 3-alkoxynonafluorocyclohexenes (83) are formed in addition to the 1-alkoxy isomers (82) from decafluorocyclohexene (81) with different alkoxides (Clayton et al., 1965). On the other hand, methyllithium and LiA1H4gave 98-100% of the vinylic substitution products (Sayers et al., 1964; Evans et al., 1963). Rearranged and unrearranged products are formed in equal amounts from 1-hydro- and 1-methylnonafluorocyclohexene. These results were again ascribed to the formation of carbanionic intermediate from which elimination is faster than internal rotation. It was also assumed that the addition and the elimination of the nucleophile and the leaving group occur in trans fashion, and therefore the leaving group has to leave from a position cis to the entering nucleophile. Competition between the cis-fluorine of the CF2 group with the trans-, but more easily cleaved, fluorine of the C(0R)F group, gives both (82) and (83). As expected by this reasoning, more (83) is formed with increase in the electron-attracting power of R. The lower stereochemical opposition to cis elimination in the smaller ring systems was thought to contribute to the higher proportion of the vinylic isomers,

B

The data for competition between formation of (19) and (20) in aliphatic systems are more limited, but they are only partly accounted for by the carbanionic theory. Attack on chlorotrifluoroethylene, for example, is nucleophile-dependent : fluorine from the CF2 group is replaced on reaction with PhMgBr (Tarrant and Warner, 1964), PhLi (Dixon, 1966) and LiNBu2 (Yakubovich et al., 1966), while Re(C0);

NUCLEOPHILIC VINYLIC SUBSTITUTION

31

and Fe(C0)2-n-C6H; ions replace the chlorine atom (Jolley and Stone, 1965). CFZ=CFRe(CO)s

Re(CO)a f---

CCIF=CFz

PhLi ___f

PhCF=CClF

The attack at the CF2 group of 1,l-dichloro-2,2-difluoroethylene by EtMgBr (Tarrant and Warner, 1954), the attack at the CF2 group of phenoxytrifluoroethylene by phenoxide ion (England et at., 1960) and the replacement of the 1-fluorine of 1-diethylaminotrifluoroethylene with water (Yakubovich et al., 1966) are in line with predictions based OP the carbanionic theory. On the other hand, the attack of triethyl phosphite at the terminal difluoro group of o-iodoperfluoro1-olefins (Knunyants and Pervova, 1962) could be explained by steric control. A competition between two strongly activating groups of l-butylsulphonyl-I-chloro-2-p-tolylsulphonylethylene results in the replacement of the p-tolylsulphonyl group by piperidine, sodium sulphide or sodium bisulphite (Backer et al., 1953). It is probable that the extra stabilization of u-chlorine coupled with the differences in basicity of the two sulphinate anions controls the direction of the reaction.

C. The Stereochemistry of the Addition-Elimination Route The stereochemical course of substitution by the addition-elimination route is related to the structure of the transition state and to the timing of the bond-forming and bond-breaking processes. The terms “retention”, “inversion” and “racemization ” will be used respectively to denote the processes in which the geometrical arrangement of thegroups in the substitution product remains the same (equation 3), or changes NU

R

(M), cis

(85), cis

(86),trans

@I), trans

(&()+Nu(86) +Nu-

___*.

Either (84) or (86)

+ Nu-

Retention

J

1

(87)+X’

(85)fX4(85) or (86)or ( 8 5 ) (86)

+

(3)

Inversion

(4)

Racemization

(5)

32

Z V I RAPPOPORT

to the isomeric structure (equation a), or processes in which the same mixture of both isomers (or only one of them) is formed from the two isomeric starting materials (equation 5 ) . These terms are not exactly analogous to those used for substitutions at a saturated carbon atom, but they are sometimes used as such in the literature. We will denote the a-substituents as M (medium) and L (large). 1. The one-step substitution Gold (1951) was the first to suggest that the stereochemical consequences of the substitution depend on the mode of nucleophilic attack, i.e. whether the attacked carbon atom of the transition state is planar or tetrahedral. A planar transition state (88) which is analogous to that of a SB2 reaction would be obtained if the nucleophile attacks in the plane of the substituents, being collinear with C j and the leaving group. bonds are sp-hybridized, one of the I n (88), the collinear R-C,-Cfi remaining p-electrons participates in the formation of

(W

(88)

(87)

.rr-bond, while the other one is involved in the weak bonding of Cfi to both the entering and the leaving groups. The stereochemical outcome of the SN2mechanism (equation 6 ) would be inversion of the configuration for both isomers, as the C,-Cj bond retains its double-bond character during the substitution. On the other hand, if a tetrahedral intermediate carbanion is formed by an sp2+ sp3 route, it should give, according to Gold, a mixture of both isomers, bond is not restricted. provided that free rotation around the C,-Cj Stereochemical data for choosing between the alternatives were not available to Gold, but it was shown with molecular models for the reaction of /3-bromostyrenes with iodide ions (Miller and Yonan, 1957) that the reaction site is highly shielded. In (88), the groups N and M (i.e. I and H) and L and X (i.e. p-O2NC6H4and Br) are almost within bonding distances and, since bond formation is impossible, the repulsion energy is high enough to exclude contributions from it. The packed geometry around the double bond results in severe steric repulsion even when smaller groups are involved, since the steric interactions of cis groups which play a role in the ground states of olefins with 120” angles around C, or C,, will be more serious in (88) with the four 90b angles

NUCLEOPRILIC VINYLIC SUBSTITUTION

33

around Cg. Moreover, a-activating groups are usually polyatomic and their bulkiness would increase the shielding of the reaction centre to attack from the plane of the substituents. The operation of the SN2mechanism was actually suggested only for the substitution of the 8-halo-a-pentachlorostyrenes with EtO- ion (Ross et al., 1952). It was shown later (Huett and Miller, 1961) that this reaction belongs to the elimination-addition category. A one-stage displacement giving retention by a front-side attack via (89)is no longer analogous to the SN2reaction, and requires distortion of the two lobes of the p-orbital involved in the substitution to ca. 110" angle. Such a structure for the transition state was dismissed for

nucleophilic aromatic substitution (Bunnett and Zahler, 1961), or for vinylic reactions (Bunnett, 1959). I n addition, an inversion mechanism would then also be required to account for those cases in which a mixture of both isomers was observed, and both (88) and (89) would have to be invoked. 2. Substitution via tetrahedral intermediate The element effects are best explained by assuming a two-step process. Recent discussions on the stereochemistry therefore dismiss the one-step mechanism and explain the stereochemical results with the aid of intermediate carbanions. We will first discuss the theory of the substitution in general form and then evaluate the experimental data according to it. The discussion is partially along the lines of those of Miller and Yonan (1957), Jones e t al. (1960) and Rappoport et al. (1963). a, The general scheme. Scheme 4 gives the various conformers of the intermediate carbanions formed by nucleophilic attack on a pair of cis-trans isomers, and which are important for discussing substitution or isomerization. It also defines,the rate constants for the various processes, where k2 with superscript is the rate constant for elimination of X- or Nu- from the conformer, and where the various rate constants for rotation, kr,t carry superscripts to indicate the angle of rotation required to form them from the conformer given as superscript. The symbols (c) and (t) differentiate between conformers obtained from cis and trans

34

ZVI R A P P O P O R T

Nu-

1

,$93'

___F

M--

NU

R

NUCLEOPHILIC VINYLIC SUBSTITUTION

36

isomers, respectively. Reactions with X- are neglected. The negative charge on the a-carbon is not shown. Scheme 4 is based on three assumptions: (A) The nucleophile attacks perpendicularly to the plane of the molecule, giving a tetrahedral arrangement of the groups around the j?-carbon. (B) The groups on the a-carbon remain planar in the carbanion. (C) Elimination of the leaving group occurs perpendicularly to the plane of the incipient double bond of the product. It should be noted that assumption (B)is not an essential one. Indeed, Miller and Yonan (1957) and Rappoport et al. (1963) discussed the substitution and the isomerization reactions in terms of a pair of rapidly inverting carbanions (94) and (95). If inversion is rapid enough, then the a-carbon atom is, on average, planar. Discussion in terms of (94) and (95) would give similar results but should be slightly modified by including both rotation and inversion rates (see also Miller, 1968). For example, 60" rotation followed by elimination from a planar carbanion, would give the same stereochemicalresults as a fast inversion, 60" rotation and trans elimination of the nucleophile and the electron pair from (94) which is formed by trans addition. I n the absence of exact NU

Nu

knowledge of the structure of the carbanion we prefer discussion in terms of planar structure, avoiding in this way the question of cis or trans elimination of the nucleophile and the electron pair. This assumption seems fair, as the carbanion itself is derived from a planar starting material. b. Retention, inversion and racernization. The primary carbanions, formed from the cis and trans isomers by the nucleophilic attack, are (90) and (93), respectively. Rotations of 0", 60°, 120" and 180" would yield conformers from which either Nu- or X- could be eliminated according to (A) and (C) above. The chemical and stereochemical courses of the reaction are summarized in Table 4. Obviously, a 0" rotation followed by elimination of Nu- re-forms (90) or (93) and is therefore not detectable directly, although some indirect data are obtained from isomerization studies (Rappoport et al., 1963). If the leaving group leaves after 60" rotation only, from con-

36

ZVI RAPPOPORT

formers (91c) and (92t), the overall result is substitution with complete retention of configuration. If it leaves after 120' rotation only, i.e. from conformers (92c)and (91t) ,the result is substitution with complete inversion. A 180" rotation followed by expulsion of Nu- from either (90) or (93) results in isomerization of the starting olefin. Complete retention for both isomers is expected only if the rate constants kJ9lc) and k2(92t),for the elimination of X- from (91c)and (91t) respectively, are much larger than the value of kfzt leading to (92c) and (91t).Retention is therefore kinetically controlled, and would be observed if bond-breaking lags but slightly behind bond formation. The difference from the one-step retention is both in the direction of the nucleophilic attack and in the timing of the bond-making and bond-breaking processes. The eclipsing pairs during the process of formation of (91c) and (92t) are (R,M) and (R,L) for the cis and the trans isomers, respectively. The requirements for inversion are more stringent. Here, bondbreaking lags more behind bond formation, and the intermediates (91c) and (92t) should be by-passed in preference to (92c) and (91t): hence kiz:(90)& kL9lC)and k:393)BkL92t). On the other hand, ki$' should be lower than ki92c)and k:tt(93) smaller than kL91t), i.e. once the conformers (92c) and (91t) are formed, they should not be by-passed by a free rotation. Inversion in preference to retention could be visualized as resulting either from a high-energy barrier to formation of (91c) and (92t) B k::t) and a low population of these conformers, or from comparable population but more difficult elimination (kiz:(90)3 kL9lC)2 k120(93) rot 9 and k:t:(90)-g kz2(c),kif:(93)
TABLE 4 Expected Steric Course in Vinylic Substitution via Intermediate Carbanions Angle of rotation

Steric course'

Chemical course

No change Substitution Substitution Substitution

180"

Retention Retention Inversion Retention + Inversion Inversion

Isomerization

> 360'

Racemization

Substitution

60°+ 120"+ 180"+ >360"

Retention + Inversion + Racemization

Substitution + Isomerization

O0

No change Substitution Substitution Substitution

180"

Retention Retention Inversion Retention + Inversion Inversion

Isomerization

> 360"

Racemization

Substitution

Retention+ Inversion + Racemization

Substitution + Isomerization

Elimination from

O0 60" 120° 60" 120'

+

60' 120° 60"+ 120"

+

+

60" 120" 180°+ >360"

Leaving group

Interacting pairs"

According to the "competition theory" (p. 39) for short-lived carbanions. According to thermodynamic control for longlived carbanions. The interacting pairs are those of the three preceding lines, depending on the degree of rotation involved. (I

w -J

38

ZVI RAPPOPORT

before X-- can be eliminated, i.e. both %:!(") and k&93)should be higher than kL9l') and k&92c). If the formation of (93) from the cis isomer, or of (90) from the trans isomer, is faster than the elimination of either Nu- or X-, then the carbanions lose their identity after 180" rotation. The stereochemistry of the product would accordingly be determined not by the configuration of the starting material, but by thermodynamic control. The same single isomer or mixtures of both isomers would be obtained from both cis and trans starting materials. Substitution would now occur via (91c = 91t) and (92c = 92t), but these are obtained by free rotation. We arbitrarily define them in Table 4 as obtained by >360" rotation, meaning that X- is eliminated when the carbanions derived from the cis and the trans isomers are no longer distinguishable. The thermodynamic controlling factor would be the "cis-effect", according to which the elimination transition states resemble the products in their relative steric interactions (Curtin, 1964; Eliel, 1962). Competition between (R,M) and (Nu,L) interactions in the transition state leading to the cis configuration, and between (R,L) and (Nu,M) interactions in the transition state for the trans product, would determine the product ratio. For example, for the same nucleophile, if R =H, the trans isomer would predominate if the (Nu,L) interactions are larger than the (Nu,M) interactions. Increase in the percentage of cis isomer is expected with increase in the size of R. With a small Nu and a bulky R group, the cis isomer would predominate owing to the larger (R,L) interaction, but for a small and constant R more trans isomer would be formed on increasing the size of Nu. We will refer to carbanions which give elimination faster than rotation, being responsible for the clean retention or inversion for both isomers, as "short-lived carbanions ". They may be short-lived if the C-X bond breaking has very slightly progressed even at (90) and in conformations on the way to (91) concurrently with the bond formation. The simultaneous development of partial double-bond character between C, and Cg creates a barrier for rotation. The conformer which requires the least rotation is formed, and the properly situated X leaves from this conformation. An alternative explanation, based on high population for conformations (91c) and (92t), seems much less likely. If the above analysis is correct, pathway (90)+ (93) is forbidden and concurrent isomerization of the starting material with clean retention in the substitution is impossible. Since retention is sometimes obtained from a combination of the addition-elimination and the eliminationaddition routes, the appearance of concurrent isomerization would point to this route for product formation rather than to addition-elimination

NUCLEOPRILIC YINYLIU SUBSTITUTION

39

alone. Similar arguments predict that isomerization of the starting material is not expected when only inverted product or a mixture of retained and inverted products are formed via short-lived carbanions. Long-lived carbanions are essential .but not always sufficient for the isomerization, as this is dependent on the relative leaving ability of Xand Nu- from the intermediate. Generally, the weaker nucleophile of the two leaves in preference, and isomerization would be observed only if the elimination of Nu- is not much slower than that of X-. c. Formation of cis-trans mixtures. The “competition theory” and the “preferred retention mechanism ”. Formation of different cisftrans product ratios from the reaction of cis and trans olefins could result from four different causes: (a) Mixture of retention and inversion routes via short-lived carbanions. (b)Mixture of retention, inversion and racemization routes via short- and long-lived carbanions. (c) Partial isomerization of the starting material before and during the substitution. (d)Isomerization of the product during and after the reaction by nucleophiles present in the reaction mixture. Since cases (c) and (d) are not directly related to the substitution, they distort the real product distribution and should be evaluated by control experiments. It is recommended that product ratios should be recorded as early as possible and extrapolated to zero reaction time. Case (c) could be recognized either by the appearance of isomerized starting material or by irregularities in the kinetics, if isomerization is faster than substitution and if the cis and trans isomers differ in reactivity. When the cisltrans ratios from both isomers are not very different from each other, racemization probably contributes to the product, although differentiation between (a)and (b) is difficult. The product ratios from the two isomers should be discussed in terms of (a)if they differ strongly. Each isomer is then assumed to be formed by a kinetically controlled process, and. the relative contributions of the retention and inversion mechanisms are given by the ratio of retained to inverted product. Vernon and coworkers (Jones et al., 1960) suggested that this ratio would be determined by competing different steric interactions during the formation of the conformer allowing elimination, rather than by the steric interactions in the transition state of the elimination itself. The cisltrans ratio obtained from the cis isomer would be determined by competition between (R,M) interaction on the one hand and (X,L) or (Nu,M) interactions, whichever the highest, on the other. The relative order of these interactions could be estimated from models and used to predict whether retention or inversion will be dominant. It can be concluded that the ratio of retained to inverted product would be different starting from the cis or the trans isomer. We will call this

40

Z V I RAPPOPORT

the “competition theory”. The predictions according to it and the above discussion are given in Table 4. Alternatively, it is possible that the very short life-time of the carbanion is the product-determining factor. Since less rotation is required for it, retention would always be preferred, and inversion would be observed only if the conformer obtained after 60’ rotation is by-passed either as a result of the stability of the carbanion, or if the rotation and the elimination rates are comparable. We will call this route in which the importance of retention, inversion and isomerization decrease in this order, the “preferred retention mechanism ”. Discrimination between conformers due to steric interactions leading to them does not play a role in determining the product ratio, and the difference in the degree of retention for each member of the pair of isomers cannot be predicted. A “steric element effect” may operate if the cisltrans ratio is determined by the competition theory. The leaving group is not involved in the (R,M) interaction which controls the amount of retention of the cis isomer, but if the (X,L) interaction is larger than the (Nu,M) interaction, it would control the amount of inversion. When compounds with X = C1 and X = Br are compared, the bulkier bromine should cause less inversion. The same arguments show that more retention is expected on increasing the size of the nucleophile. Another prediction is that more inversion would be obtained for both isomers on increasing the size of R. For thermodynamic control more retention is expected for the cis isomer on increasing the size of R, but more inversion for the trans isomer. This difference may be of some value for differentiation between kinetic and thermodynamic control. It should be emphasized that the stereochemistry should be studied for both isomers, since work with one isomer only can result in wrong identification of the substitution mechanism. Table 5 summarizes the stereochemical information available for reactions which are assumed to follow the addition-elimination route. Unfortunately, the reliability of the data is not the same for all the systems. Earlier work, where minor products were neglected and proper control experiments were not performed, is subject to some uncertainties. For example, when 100% of one isomer was reported, this generally means that only one product was isolated. Recent data, obtained with more sensitive and less destructive methods, such as NMR,are much more reliable. The data are arranged by grouping together reactions with the same type of nucleophiles and discussed in the same order. Mechanisms involving retention, mixture of retention and inversion and racemiza-

TABLE5 Steric Course in the Addition-Elimination Route

Substrate" cis-ClCH=CH. CN

Nucleophile p-MeC.&S-

cis-MeCCl=CH. CN tram-MeCCl=CH. CN) cis-MeCCl=CH .CN tram-MeCCl=CH .CN c i s - M e C B d H .CN tmm-MeCBr=CH. CN) cis-MeCBr=CH.CN

PhS-

I

EtSPhSEtS-

&-Arc0.CH=CHCI tram-ArCO. CH=CHCl) (&=C&, p-ClCsH4, p-MeOC&)

1

c ~ s - A ~ CC OH . dHC1 tram-ArCO. C H d H C l C i s - C l C H d H . COzH

PhS-

p-NOzCsH4S-

ArS-

Substitutionb product %trans yocis 95 10 > 97 <2 > 98 1 2 98 3 97 4 100 5

100 0 100

0

Steric course of

reaction

5 90 <3 >98

Retention

Scotti and Frazza, 1964

Retention

Theron, 1967

t2

Retention

Theron, 1967

Retention

Theron, 1967

Retention

Theron, 1967

Retention

Angeletti and Montanari, 1958; Landini and Montanan, 1967

Retention

Angeletti and Montanari, 1958 Montanan, 1956; Angeletti and Montanari, 1958

>98 2 97 3 96

0 95

0 100 0 100

Retention

(Ar= C6H5, p-MeCeH4, p-NOzC&) cis-PhCBr=CH. COzH t r a m - P h C B d H . COzH tram-MezCHCCl=CH. COzEt cis-MeCCI=CH. COzEt t r a m - M e C C l d H . COzEt

I

ArSPhSPhS-

Reference

Isomer mixture Isomer mixture 100 0 95 5 3 97

Racemization? Retention Retention

Angeletti and Montanari, 1958 Pizey and Truce, 1965 Pizey and Truce, 1965

TABLE &-continued

Substrate5

Nuc!eophile

Substitutionb product %cis %trans

Steric course of

reaction

Reference -

cis-MeCCl=CH .COzEt trans-MeCCl=CH.COZELI cis-MeCCl=CH. COzEt trans-MeCCl=CH .COzEt

I

95 0 91 15

5 100 9 85

Retention

Pizey and Truce, 1965

Retention or Retention + Inversion Retention or Retention Inversion Retention or Retention + Inversion Retention

Jones et al., 1960 Theron, 1967

c i s - M e C B d H . COzEt t r a n s - M e C B d H . COzEt

PhS-

94 4

6 96

c i s - M e C B d H .COzEt t r a n s - M e C B d H . COzEt

EtS-

94 6

6 94

100 0 100 0

0 100 0 100

100 0 100 0

0 100 0 100

Retention

100 100

0 0

Retention Retention

Maioli et al., 1960 Maioli et al., 1960

100

0 0 100

Retention Retention

Maioli et al., 1960 Angeletti and Montanari, 1958

ck-p-NOzC6H4.SO. C H d H B r p-NOzCaHrStvans-p-NO&aH~.So.CH=CHBr] cis-ArSO .C H d H C 1 A&trans-ArSO .CH=CHCl) (Ar=C&, p-NOzCaH4, P - C l c d h ) cis-PhSOz. C C l d H C l PhStrans-PhSOz .CCl=CHCl) cis-ArSOz .CH=CHCl PhStvans-ArSOz.CH=CIICI] (Ar=C&. p-ClC,~H4,p-MeCd%, p-NOz. CsH4) cis-ArSOz. CH=CMeBr PhScis-ArSOz. CH=CMeCl PhS(Ar=p-NOz. CaH4, p-MeCeH4) cis-ArSOzCMdHCl PhSc i s - A r C B d H . COzH PhSt r a n s - A r C B d H COzH (h=p-NOz.C6H4, m-NOz. CSH4)

.

100 0

+

Retention

Retention

Theron, 1967 Montanari and Negrini, 1959 Modena, 1958; Montanari and Negrini, 1959 Montanari and Negrini, 1957a Modena, 1958; Modena and Todesco, 1969

C~~-CH(CHO)=CHSCN cis-MeC(N02)=CMeN02 tra~-MeC(N02)=CMeNOz tram-p-MeCa4.SCCl=CHCl cis-Arc0 .C H d H C l tram-ArCO CH=CHCl (AX!= C6H5, p-NOZ.C6H4) trans-PhCO CH=CHNMe:Cl-

. .

Cis-PhSOzCCldHCl trans-PhSOaCCl=CHCl] tram-MeCO.CH=CHCl c~~-P~CC~=CHNOZ trans-PhCCl=CHNOz cis-ClCH=CHCN trans-ClCH-CHCN cis-ClCH4H.COzH trans-ClCH=CH. COzH cis-ArSOzCH4HCl

PhSO;

PhSO, CNSCNSEt2NCSS-

ArSeN,

cis-p-MeCsHg.SOz. CH=CH. SOz. C&Me-p tram-p-MeCsH4.S O z . CH=CH. SOz. CsH4Me-p cis-MeC(NOz)=CMeNOz N, trans-MeC(N02)=CMeNOz

100 0 100 0 100 0 90 0 0 0 0 0 100

0 100 0 100 0 100 10 100 100 100 100 100

100 0

0 100

0

100

Retention?

0 100 100 1ood 1008

Retention

100 0 0 Od Od

1000 OC

100 0 100 0 90 0 100' 0"

-

0

00

l0OC 0 100 0 100 10 100 0 ' 100'

Retention

Marchese et al., 1968

Retention

Marchese et al., 1968

Retention

Beltrame and Beltrame, 1968 Meek and Fowler, 1968

Retention Racemization?

Rasp, 1966

Racemization

Emmons and Freeman, 1957 Truce and Kassinger, 1958a Angeletti and Montanari, 1958

Inversion or Racemization Retention

Retention? Racemization?

Rybinskaya and Nesmayanov, 1966 Montanari and Negrini, 1957a Benson and Pohland, 1964 Iwai et al., 1965

Retentionc

Bikales, 1965

Retention

Chierici and Montanari, 1956 Modena and Todesco, 1959 Meek and Fowler, 1968

Retention Retention Racemization?

2

4

d F M 0

Emmons and Freeman, 1957 IP

W

TABLE&-continued

Substrate'

Nucleophile

cis-ClCH=CHCN tmns-ClCH=CHCN) c ~ s - A ~ S OCZH . 4HC1 tran.s-ArSOz. C H d H C l ) cis-p-MeCaH4. SOz. C H d H . SOz. CeH4Me-p trans-p-MeCsH4. SO2 .CH=CH. SOz. CsH4Me-p cis-CF3. CCl=C(CF3)Cl' trans-CF3. C C l d ( C F & I ' )

95 5 100 0 95

EtOMeO-

] MeO-

cis-CF3.CCl=C(CF3)C1' traw-CF3. CCl=C(CFs)Cl' ciS-CF3. CCI==C(CF.q)Cl' trans-CFs. CCId(CF3)Cl' cis-MeCCl=CH. COzEt t r a n s - M e C C l d H.COzEt cis-p-NOz. Cs&CH=CHBr trans-p-NOz.CsH&H=CHBr) cis-p-MeOCaH4CPh=CHCl'

I

MeO(0°) EtO- ( 2 5 0 ) (50") (25") i-Pro-

ArO-

IC1-

trans-p-MeOCaH4CPhdHCli trans-MeCOCH=CHCl cis-ClCH=CHCN tras-ClCH=CHCN] cis-ArSOzCH=CHCl

I-

Substitution* product yocis %trans

(170') (186') (170") (186') . .

Piperidine Cyclohexylamine

0 93 31 97,2 94.5 94.9 30 96.5 28 100 100 ca. lOOh ca.Oh 60 56 22 28 0 0 0 0 0

5 95 0 100 5 100 7 69 2.8 5.5 5.1 70 3.5 72 0

Steric course of reaction

Reference

Retention

Scotti and Frazza, 1964

Retention

Maioli and Modena, 1959

Retention

Meek and Fowler, 1968

Retention + Inversion Retention + Inversion

Park and Cook, 1965 Park and Cook, 1965

Retention + Inversion Racemizationg

Park and Cook, 1965

0

Jones et al., 1960

Y

N

td k-

ld ld

0

ca. OA ca. lOOA 40 44 78 72 100 100 100 100 100

2

Retention

Miller and Yonan, 1957

Retention + Inversion

Beltrame et al., 1966

Retention? Racemizationj

Benson and Pohland, 1964 Scotti and Frazza, 1964

Racemizationj

Modena et al., 1959

0 'd

td

c ~ s - A ~ S OCZ H . dHCl trans-ArSO~.C H d H C 1 )

BuzNH

c G - A r S O z .C H d H C I trans-ArSOz .CH=CHCl)

MezNH

1

C&'-~-M~C~H~.SOZ. C H d H .SO2 .C6H4Me-p tr~m-p-MeCsH4.802.CH=CH. SO2 .CaH4ME-p c~~-RC(NO~)=C(NOZ)R ~v~~~-RC(NO~)==C(NO~)R (R=Me, Et, Ph) ow-PrC(NOz)=C(NOz)Me tram-PrC(NOz)=C(N02)Me cis-ClCHdHCN trana-ClCHdHCN) c~s-A~SO C ZH. d H C I trans-ArSOz .CH==CHCl]

I

cis-p-MeCgH4.SOz. C H d H . SOz. C,&Me-p truns-p-MeCaHa. S O z . C H = C H . SOz. CsH4Me-p)

Cyclohexylamine

0 0 0 0 0 0

Amines Amines

(MeZN)zC=NH NH

/ \ CHz-CHz NH

/ \

look

Racemizationj

Modena et al., 1959

rno

Racomization j

Ghersetti et al., 1965

100 100 100

Racemization'

Meek and Fowler, 1968

100 100

@ Ok

Racemization j

lOox

Emmons and Freeman, 1957

1od

0 '

Racemization'

1oox 100 0 100 0

0 100 0 100

Retention

Emmons and Freeman, 1957 Fanshawe et al., 1965

Retention

Truce el aZ., 1967

100 0

0 100

Retention

Meek and Fowler, 1968

100

0 100

Retention

Truce et al., 1967

0 5

d

CH-CHz c i s - C I C H d H .COzEt t r a n s - C l C H d H .C02Et) trans-MeCO. C H d H C 1 Ck-PhCCldHNOz tram-PhCCl=CHNOz trans-PhSOz .C H d H B r tra~-(CHB~CH)zSO,' cis-p-MeC&4.S0~.C H d H . SOz. CeHaMe-p tr~ns-p-MeCsH4.S O z . C H d H . SO2 .CaH4Me-p cw-ClCH==CHCl trana-CiCH=CHCI]

I

cis-PhCHdHBr tram-PhCHdHBr

NH

/ \ CHz-CHz NMe3, MezNH Morpholine P(OEt)3

PhZPPhzP-

95

loor look

ox ox

Retention? Racemizationj

Benson and Pohland, 1964 Iwai et al.. 1965

0 0 0 0 100 0 100 0

100 100 100 100 0 100 0 100

Retention? Retention? Racemization

Kataev et aZ., 1965 Kataev et al., 1965 Meek and Fowler. 1968

'

Retention

Aguiar and Daigle, 1964

Retention

Aguiar and Daigle, 1964, 1965

Substrate” ck-PhCH=CHBr trum-PhCHdHBr) trans-PhCHdPhBr trans-MeCO.CH=CHCI ck-MeCCI=CH.COzEt tram-MeCCI=CH.COzEt tram-MeCO.C H d H C I cis-ClCHdH.COzH truns-ClCH=CH.COzH ois-ClCHSH.COzH &um-CICH=CH.COzH cW-CICH=CH.COzMe trans-ClCHdH .COzMe ck-p-MeCeH4.S 0 2 . CH=CH .SOz .C6Hae-p

Nucleophile PhzAsPhzAsCNCH(C0zEt)z CR(C0zEt)z MeMgBr PhMgBr PhMgBr, CuCl PhMgBr

Substitutionb product %cis %trans 100 0 100

0 100 0

0 100 0 0 81 4 99 10 99 9 0

100 0 100 100 19 96 1 90 1 91 100

Steric coupse of

reaction Retention Inversion or Retention?m Retention? Retention Retention? Retention + Inversion?“ Retention + Inversion?n Retention+ Inversion?” Inversion or Racemization?”

Reference Aguiar and Archibald, 1967 Aguiar et al., 1967 Benson and Pohland, 1964 Gidvani et al., 1932 Kochetkov et al., 1961 Gafni, 1965 Klein and Gafni, unpublished Klein and Gafni, unpublished Meek and Fowler, 1968

The t e r n “cis” and “tram” refer to the activating and the leaving groups unless otherwise stated. * Obtained as close as possible to kinetically-controlledconditions. A different product was isolated from each isomer, but the geometricalconfiguration was not determined. Only one product was isolated from both isomers, but its structure was not determined. The product is a substituted furoxan, obtained by elimination of nitrogen and cyclization. ’“ci8’’ and “tram” refer to the chlorine atoms. Probably results from a /3,y-eliminationaddition. A Products were determined indirectly. The kinetic analysis showed that retention is the main pathway at early stages. ‘‘ck” and “tram” refer to the anisyl and the chlorine substituents. j Probably results from a post-isomerization,see text. One product was claimed to be isolated, but its structure was not determined. Owing to the strong hydrogen bonding in the cis configuration we assume this The result is probably for thermodynamic control, since the other isomer to be the product. Only one bromine was substituted. isomerizeseasily to that observed. The primary products reacted further with excess reagent. The values for the percentage of the isomers are probably only approximate. Only small amount of material was isolated by chromatography, in conditionswhich may cause isomerization.

NUCLEOPHILIC VINYLIC SUBSTITUTION

47

tion are apparently needed in order to account for the experimental results. d. Reactions with thio-nucleophiles and with azide ion. Retention is clearly preferred for nucleophiles having high carbon nucleophilicity and relatively low hydrogen basicity, such as the sulphur nucleophiles (thioethoxide, thiophenoxides, sulphinate, dithiocarbamate ions), arylselenide and azide ions. The combination of a highly active nucleophile aad a good a-activating group renders most of these reactions facile enough even at room temperature. Thus, p-halovinyl derivatives activated by arylsulphoxide (Modena, 1958; Montanari and Negrini, 1959), arylsulphonyl (Maioli et al., 1960; Modena, 1958; Modena and Todesco, 1959), carboxyl (Autenrieth, 1887, 1889, 1890, 1896; Montanari, 1956, 1958; Montanari and Negrini, 1957), carbethoxy (Scheibler and Voss, 1920; Jones and Vernon, 1955; Morris et al., 1958; Jones et al., 1960; Pizey and Truce, 1965; Theron, 1967), cyano (Scotti and Frazza, 1964; Theron, 1967), aroyl (Angeletti and Montanari, 1958; Landini and Montanari, 1967) and mono- and di-nitrophenyl groups (Marcheseet al., 1968) gave complete retention of configuration for both isomers. Shortlived carbanions are therefore essential in these systems and no isomerization of the starting material should be observed. Indeed, no evidence of such isomerization, either by change in the rate constants during a run, or by actual isolation was reported. Isomerization of some products was reported, however, e.g. the trans-a-aroyl-/I-arylthioethylenes obtained by substitution of the correspondingchloro-derivatives, isomerized with excess base to the cis isomers (Landini and Montanari, 1967). Earlier work on the substitution of ethyl p-chlorocrotonates by PhSion (Jones et al., 1960) have indicated less retention (85% for the cis and 64% for the trans isomer, where cis and trans refer to the methyl and the carbethoxy groups) than reported in the more recent and accurate investigation of Pizey and Truce (1965) (97% and 95% retention, respectively). No new data are available for the EtS-/p-chlorocrotonate reaction which gave 85% retention for the cis and 91% retention for the trans isomer. The somewhat higher degree of retention (88%) from the cis isomer after shorter reaction times, may point to a kineticallycontrolled higher degree of retention, as found for the PhS- reaction. The values were, however, analyzed by Jones et al. in terms of the competition theory. The models predict that retention with eclipsing (Me,C0,Et) and (Me,H) pairs for the cis and the trans isomers, respectively, would be preferred over inversion with the corresponding (C02Et,Cl), (EtS, H) and (EtS, CO,Et), (Cl, H) eclipsing pairs. While this analysis is in agreement with the experimental results, it is difficult to understand why complete retention would be observed with PhS-

48

ZVI RAPPOPORT

but not with IZtS-. The 94-98% retention for the corresponding bromo esters and the bromo- and chloro-crotononitriles with both thio-nucleophiles (Theron, 1967) suggest that the actual degree of retention is probably higher than reported. The competition theory also predicts more retention with a bulkier nucleophile. Ethyl /?-chlorocrotonate showed more retention with mesitylthiolate ion than with thiophenoxide ion, but it is of little diagnostic value as in both cases the degree of retention was very large. The prediction that increasing size of R would lessen retention was not borne out. Pizey and Truce (1965) found that reaction of (96) with PhS- gave complete retention for R =Me or i-Pr, and Maioli et al. (1960) had shown that retention is the only pathway for the (97)-PhS- reaction with R = H or Me. Retention is therefore preferred even if the (i-Pr, C0,Et) interactions during the 60" rotation are higher than either R,

,COzEt

C1,

,SOzAr

C1

'H

R

'H

,c=c

,c=c

the (PhS, C0,Et) or the (Cl, H) interactions during the 120' rotation. A more rigorous test of the competition theory would be to increase further the size of R in order to find out at what degree of steric interactions retention would cease to be the exclusive pathway. From the above it is clear that groups which are usually known as capable of stabilizing carbanions do not make the life-time of the carbanion long enough for free rotation. The substitution could be visualized as occurring within the carbanion by an internal SN2reaction with the electron pair of the a-carbon attacking with .rr-bond formation, while concurrently the C-X bond is broken. Hence, the greater the ability of the activating group to spread the negative charge, the smaller should be the nucleophilicity of the electron pair and the longer the life time of the carbanion. However, the experimental evidence is that even when the charge-spreading capacity of the a-group is changed by a large factor, e.g. from nitroaryl to aroyl, retention is still exclusive and the carbanions are still short-lived. Nevertheless, continued increase in the activating power of the a-substituent should finally result in racemization. This could be obtained by using an a-nitro group or two a-activating groups. Indeed, in the reaction of cis- and trans-3,4dinitro-3-hexcne with p-toluenethiolate or azide ions, the same product was obtained from both isomers (Emmons and Freeman, 1957). This was ascribed t o the formation of a long-lived intermediate in agreement

NUCLEOPHILIC V I N Y L I C SUBSTITUTION

49

with our prediction, but another explanation is possible : for groups such as nitro or cyan0 which are not usually cleaved when attached to a saturated carbon, the cleavage of the C-X bond is slower than the internal rotation. This is reminiscent of the substitutions of XC(CN)= C(CN)2 with N,N-dimethylaniline. When X = CN, the proton leaves before the cyanide ion, while when X = C1, C-C1 bond-breaking precedes the C-H bond breaking (Scheme 3). I n addition, the possibility that a post-isomerization is fast owing to the powerful activating a-nitro group cannot be dismissed. The formation of only one isomer from the with substitution of cis and trans a-nitro-/3-chloro-/3-phenylethylenes thiocyanate ion (Iwai et al., 1965) which was shown to have the trans configuration (Rappoport and Hoz, 1968)may point to the racemization mechanism, but control experiments were not conducted. This system is now being reinvestigated. The apparent racemization in the formation of only trans-3-p-nitrothiophenoxypropenal from both cis- and trans-thiocyanatopropenal (Raap, 1966) may be due either to the use of the leaving thiocyanato group, which should be a worse leaving group than the halides, or to a post-isomerization reaction ; the necessary control experiments were not carried out. There are no data regarding the stereochemistry for systems with two strong a-activating groups, but even the carbanions formed from such compounds may react further before complete rotation. Sodium hypochlorite oxidation of cis and trans (98) gave epoxides with retained R1R2C=C(CN)C02Et (98)

geometrical arrangement of the substituents (Robert, 1966). Here, the internal attack on the hypochlorite oxygen should be faster than the rotation in the carbanion. There are two systems in which substitution with arylthio anions does with trans not give sole retention. l-p-Tolylthio-l,2-dichloroethylene chlorines gave withp-toluenethiolate ion only the 1,2-bis(p>-toluenethio)chloroethylene with trans arylthio groups (Truce and Kassinger, 1968a). Since the other isomer was not investigated, the reaction may belong to either the inversion or the racemization category. The reaction conditions are much less drastic than those required for eliminationaddition. The competition theory would favour retention with (H, C1) interaction, over inversion with (Cl,SAr)interactions. On the other hand, for thermodynamic control, it is possible that the (SAr, SAr) (H, Cl) interactions are higher than the (SAr, C1) (H, SAr) ones and the reaction is directed towards the trans product. This relatively unstabilized

50

ZVI RAPPOPORT

carbanion seems therefore long-lived enough to give complete racemization. A possible explanation is that the carbanion is so nucleophilic that it is protonated very rapidly to give the a#-adduct. Once this is formed, it rotates faster than it eliminates HCl, therefore giving the more stable product (Truce, 1967). Mixtures of isomers were obtained from the reaction of cis- and transa-bromocinnamic acid with arylthiolate ions (Angeletti and Montanari, 1958). The corresponding m- and p-nitro acids reacted faster but gave complete retention. The slower reaction of the unsubstituted acids was probably followed by isomerization of the product, since /l-thioacrylic acids iaomerize in similar media (Montanari, 1960). Solvent was found to affect the cisltrans ratio of the products. Thus, cis- 1,2-di-p-toluenesulphonylethylene gave 90 and 80% retention with thiophenoxide ion in ether and methanol, respectively, while azide ion gave 90% retention in aqueous acetonitrile and lower degrees of retention in dimethyl sulphoxide and in aqueous methanol (Meek and Fowler, 1968). Since isomerization was found to take place in the last case, the significance of the other results is not clear, although it may be expected that in systems which are prone to racemization, a solvent effect on the cis/trans ratio will be observed. e. Reactions with alkoxide ions. I n substitution with the strongly basic alkoxide ions, the intervention of an elimination-addition for the cis isomer can complicate the stereochemicaloutcome. Retention was found for the reactions of EtO- ion with cis- and trans-/3-chloroacrylonitriles (Scotti and Frazza, 1964) and MeO-, EtO- and PhO- ions with a-arylsulphonyl-/3-chloroethylenes(Maioli and Modena, 1959). The reaction of MeO- and EtO- ions with cis-p-MeC,H,SO,CH=CRCl (R=H, Me) (DiNunno et al., 1966) showed the intervention of eliminationaddition (p. 86) but both routes gave retention of configuration. EtO-, PhO- and p-NO,C,H,O- ions gave in each case the same ether from both ethyl p-chlorocrotonates (Jones et al., 1960). It was shown recently that EtO- ion reacts via the p,y-elimination-addition route (Theron, 1967), which probably also operates for the other alkoxides. Formation of both isomers (100 and 101) from the reaction of alkoxide ions with cis-(99) and truns-2,3-dichlorohexafluoro-2-butene(102) (Park and Cook, 1965) should result from a genuine addition-elimination since elimination-addition is impossible, and there was no isomerization of the starting olefin. MeO-, EtO- and i-Pro- ions gave 95+2% retained cis ether (100) from the cis isomer (99), and 70 f 204 trans ether (101) from trans-(102). The preferred retention points to short-lived carbanions. If CF, interactions are the larger ones, as suggested by the models, the competition theory predicts predominant inversion for (99)

but less so with the bulkier i-Pro- than with MeO-; (102) should give either equal amounts of (100) and (101) or excess retention, which would decrease with the size of the alkoxide ion. None of these predictions is fulfilled. However, if the order of steric interactions is C1> CF3>OR, as suggested by the preference of the trans isomer from the 1,1,2-trichlorotrifluoro-1-propene-alkoxide reaction (Cook, 1967), the competition theory predicts more retention for the cis isomer. These results also fit the “preferred retention mechanism ”, although the different degree of retention for the two isomers is not explained. Formation of both (100) and (101) requires that the carbanions (103) and (104) have longer life-times than those carrying only one cyano or one arylsulphonyl group. Although CF3 is less activating than these OR

I

(103)

OR I

(104)

groups, the additional charge delocalization by the a-chlorine and the P-CF, substituents is apparently enough to increase the life-time of the intermediates. f. Reactions with halide ions. Halide ions (excluding F-) are not expected to have high nucleophilicity towards an sp2-hybridized carbon atom (Johnson, 1967). Substitution by halide ions was investigated only for two systems activated by the a-aryl group. p-Bromo-p-nitrostyrenes in n-butylcellosolve showed preferred retention with iodide ions (Miller and Yonan, 1957),although its exact degree was not determined, and the reaction was analysed in terms of inversion and rotation in tetrahedral intermediates (94) and (95). With the progress of thereaction all the four isomeric bromides and iodides were formed from either isomer. If the substitution occurred with pure retention, neither the excess nucleophile nor the leaving group could cause isomerization. Actually,

ZVI RAPPOPORT

52

isomerization was found, and it may be concluded that the substitution gives both retention and inversion. However, the low reactivity of the series required the use of high temperatures, and isomerization could be obtained by reversible addition of the solvent to the double bond. A combination of retention and inversion is in line with the results for the second system. Beltrame et ul. (1966) followed the chlorine exchange and the concurrent isomerization of the two isomers of l-p-anisyl-lphenyl-2-chloroethylene (105 and 106) with labelled chloride ion (CI-*) in dimethylformamide. The same steric interactions are An

\ /c' /c=c

I'h

\H (105), cia

An\

,c=c

/H

An =p-MeOCsHa

Ph \c1 (106), trans

expected for both elimination transition states (107 and 108) [(H, An), (Ph, Cl) and (H, Ph) and (Cl, An), respectively], assuming that anisyl interactions are nearly equal to phenyl interactions. Thermodynamic control predicts nearly equal amounts of cis and trans substitution products. Since, in the absence of chloride ion, no isomerization took

An--

c1*

H (108)

place, a common intermediate for the substitution and isomerization seems plausible. Such an intermediate, e.g. (109), formed by attack on the cis isomer (105) was assumed to be involved in four routes for elimina(105) +C1-

cia-Cl+c1-* trans-Cl+ c1- *

*

c1*

2

+

cis-c1* Cl-

An--&---

El

c1

H (109) SCHEME 5

trans-C1'

+c1-

53

NUCLEOPHILIC VINYLIC SUBSTITUTION

tion of the chloride ion, as shown in Scheme 5. It was also assumed that there is the same chance of retaining or inverting configuration along path (1) as along path (2) : this is required if (109) has indistinguishable chlorine atoms, i.e. kl= k2. With this assumption, the exchange-rate is half of the rate constant for formation of (109), and constant (kexch) the fraction of inversion for each isomer is ki/2kexch,where ki is the isomerization-rate constant. The results (fifth column of Table 6) show preferred retention for both isomers, which increased with decrease in temperature. The higher retention of (106) was ascribed to a lower stabilization of (108) in which the chlorine atoms flank the anisyl group, compared to (107) in which they flank the phenyl group. Higher electrostatic repulsion between the chlorines and the anisyl ring, results from the + T effect of the methoxy group. TABLE 6 Rate Constants and Stereochemical Course for the Reactions of (105) and (106) with Labelled Chloride Ion

Isomer &-(105)

t,'C

170 t r a ~ ~ - ( 1 0 6 )170 &-(105) 186 t r a ~ - ( 1 0 6 ) 186

yo Retention

yo Retention by

10%e,,,

lo%,

by Scheme 6

kinetic control

3.10 5.36 13.0 20.1

2.47 2.37 11.4 11.2

60 78 66 72

20 64 12 44

Since cis-C1, cis-Cl*, trans-Cl* and trans-C1are formed by 0", 60", 120" and 180" rotations, respectively, if (107) is symmetrical with respect to the chlorine atoms, the carbanion is long-lived and the same cisltrans ratio is expected from both isomers. The explanation of the higher retention for the trans isomer by using (107) and (108) is equivalent to discussion in terms of short-lived carbanions. Retention and isomerization via short-lived carbanions requires that each act of retention or inversion would be accompanied by exchange, and no truns-C1 is expected. Dissection of the exchange rate into retention and inversion contributions by assuming kinetic control (last column of Table 6) shows high inversion for the cis isomer and similar contributions of retention and inversion for the trans isomer. Since both the "preferred-retention mechanism " and the " competition theory " predict more retention for both isomers, this analysis is inconsistent with the results. Unfortunately, difficulties in the separation of the isomers (Beltrame,

64

ZVI R A P P O P O R T

1967) prevented the determination of the amount of exchange in the inverted product alone. Such an approach would be valuable, as the inverted product should contain either half of the labelled chlorine or none, according to whether the carbanion is long- or short-lived. The formation of mixtures from (105) and (106) is interesting in view of the retention observed for more activated systems. The high reaction temperature is probably responsible, since extrapolation of the values of the degree of retention at the two temperatures to room temperature predicts complete retention for both (105) and (106). g. Reactions with amines and related nucleophiles. With amines as nucleophiles, either retention or formation of the more stable trans enamines was observed. The stereochemical course seems to be independent of the activating group, since a-arylsulphonyl-/3-chloroethylenes give both retention (Truce et al., 1967) or only trans-enamines (Modena et al., 1959), and the same is true for reactions with /3-chloroacrylonitrile (Scotti and Frazza, 1964; Fanshawe et al., 1965). It is more dependent on the amine involved, since only trans isomers are formed from cyclohexylamine, dimethylamine, di-n-butylamine or piperidine, whereas ethyleneimine and N,N,N,N’-tetramethylguanidine give enamines with retained configuration. If the trans isomers arise from long-lived carbanions, the (H, CN) and (H, C,H,,NH$) interactions should be lower than the (H, H) and (CN, C6HloNH,+)ones for fi-chloroacrylonitriles, and the (H, R,NH$), (H, ArSOz) interactions should be lower than (H, H) and (Adoz,RzNH$) ones for the a-arylsulphonyl-fichloroethylenes. Whereas it is possible that the (amine,activating group) interactions are the largest ones, this analysis could not be applied to the ethyleneimine and the tetramethylgunanidine reactions which give kinetically controlled products. Owing to the high basicity of amines, it may be argued that the trans isomer gives retention via the addition-elimination route, whilst the cis isomer reacts by a,fi-elimination-addition.Modena and coworkers (Modena et al., 1959; Ghersetti et al., 1965) dismissed the latter route in alcoholic solvents on kinetic and stereochemical grounds, assuming that trans addition of the amine to the intermediate sulphonylacetylene would give the cis product. McMullen and Stirling (1966a, 1966b) and Winterfeldt and Pruess (1966) have recently shown that the stereochemistry of the addition of amines to activated acetylenes is more complicated (Winterfeldt, 1967). Secondary amines usually give the trans-enamines, e.g. the addition product of piperidine and cyanoacetylene is identical with the substitution product of /3-chloroacrylonitriles with piperidine (Scotti and Frazza, 1964). Ethyleneimine is an exception since it gives only cis-enamine by addition t o ethyl propiolate

NTJCLEOPHILIC V I N Y L I C S U B S T I T U T I O N

55

(Dolfini, 1965; Truce and Brady, 1966). Primary amines give mixtures, the cisltrans ratios of which are dependent on the structure of the acetylene, the amine and the solvent. Both McMullen and Stirling (1966a) and Truce and Brady (1966) found that the enamines primarily formed, except those of ethyleneimine, give subsequently the stable trans isomers, and elimination-addition for the cis isomer would therefore give inversion rather than retention. Hence, whatever is the structure of the kinetically controlled product, the rule of trans-addition (resulting in cis isomers)which applies to the reactions of thioanions with acetylenes (Truce, 1961), is not adequate for addition of amines. Eliminationaddition for both isomers is contradictory to the rate criteria (p. 77) since the substitution rate is similar for both isomers of P-chloroacrylonivalues for a-arylsulphonyl-p-chloroethylenesare trile, and the keis/ktrafis similar to those for good carbon nucleophiles (Table 7). Until recently, no satisfactory explanation for the behaviour of amines had been given, although the difference from azide or thioanions was thought to arise from the different charge type of the reactions. Since the ethyleneimine enamines are expected to survive without isomerization, the formation of retained enamines in both ethanol and benzene solution for the reactions of ethyleneimine with cis- and trans-ethyl p-chloroacrylates, a-arylsulphonyl-/?-chloroethylenes(Truce et al., 1967) and 1,2-di-p-toluenesulphonylethylenes (Meek and Fowler, 1 968) argues strongly for a kinetically controlled retention with amines. This is followed by a rapid isomerization to the trans-enamine in the cases of initial formation of cis-enamine. Such isomerization could be described by equation (7) (McMullenand Stirling, 1966a)and it was shown recently by NMR that the enamines (lll),where X,=X,=CO,Me or COMe,

show free rotation around the C,-Cp

bond even at room temperature.

H\ ,C='C Me2N

'x2

(111)

Ethyleneimine enamines do not isomerize owing to the inhibition of formation of (110) as a result of the angle strain involved. A confirmation ofthis hypothesis is that the reaction of N,N,N,N-tetramethylguanidine with /?-chloroacrylonitrilegives the retained enamines (Fanshawe et al., 3

56

ZVI RAPPOPORT

1966) since isomerization again requires the creation of strain at the nitrogen of (110). On the other hand, there should be no such hindrance to the formation of (110) in the other amines studied, and transenamines are formed. According to this hypothesis both neutral and anionic nucleophiles react by the same retention mechanism, and the difference in the structure of some of the products arises from a, post-isomerization step. An alternative explanation is based on the charge type of the reaction. The zwitterions which are initially formed on reaction with amines show two characteristic features: (a) The conformers (112) and (114) with eclipsed nucleophile and electron pair have extra stabilization resulting from the interaction of opposite charges. (b) An ammonium proton is available in the vicinity of the negative charge. +

4.

I

(112)

X(113)

(114)

As a result of (a), an electrostatic barrier restricts the rotation, thus increasing the life-time of the zwitterionic conformer (112), and it was suggested that the rate of elimination of N from (112) is higher than the f12)) et al., 1963). Moreover, rate of internal rotation ( k ~ ~ ~ 1 2 ) > k(Rappoport the nucleophilicity of the electron pair on the a-carbon atom decreases by interaction with the positive charge and, when rotation around the C a 4 p bond takes place, conformer (113) is traversed rapidly and, once (114) is obtained, thermodynamic control takes over. I n addition, as a result of (b), protonation may be faster than the 60" rotation, forming (115) in an almost concerted cis addition. I n (115) the electrostatic barrier to rotation disappears, and rotation could again be faster than the elimination of HX, resulting in thermodynamic control. The zwitterionic hypothesis could be tested by using the anion of the amine as the nucleophile, making the primary intermediate a carbanion

57

NUCLEOPHILIC VINYLIC SUBSTITUTION

rather than zwitterion. The reaction of trans-8-chloroacrylonitrilewith lithium piperidide gave low yield of only the trans-enamine (Scotti and Frazza, 1964), with the main reaction being polymerization. The experiment is inconclusive since trans-enamine would be formed by either thermodynamic or kinetic control. However, the approach is promising in deciding between the two hypotheses, since post-isomerization of retained material would predict formation of trans-enamine from both the amine and its anion. The zwitterionic mechanism can account for the retention in the tetramethylguanidine reaction if the positive charge is carried by the two more basic dimethylamino groups rather than by the nitrogen bound to the 8-carbon of (116).

No such explanation is possible for ethyleneimine, and the experiments with this nucleophile are the best argument for the retention mechanism. On the other hand, some evidence for the longer life-time of the intermediate formed with amines may be inferred from the formation of small amounts of (116a) from piperidine and 8-chloroacrylonitrile, in addition to the main substitution product. (116a) is also the sole substi=Ph, R2=H) but no such products were tution product with aniline (R1 reported for reactions with oxygen or sulphur nucleophiles. For formation of (116a) the initially-formed carbanion should be long-lived enough as to attack another 8-chloroacrylonitrile molecule (Scotti and Frazza, 1964).

.

RIRaN. CHCl CHCN + CICH=CHCN

-

+ R1R2N. CHCl .CH(CN) .CHCl .CHCN + R1RZN. CH=C(CN). CH=CHCN (116a)

An indirect way for estimating the relative life-times of a pair of isomeric zwitterionic intermediates can be obtained from the work of Meek and Fowler (1968). Ethyleneimine and 1,2-di-p-toluenesulphonylethylenes give not only the retained vinylic enamines, but also the addition product (116b). Since (116b) is stable t o elimination in the reaction conditions, substitution and protonation are competing processes.

58

(116b)

The ratio of addition to substitution products was 0.5 and 9 for the cis and the trans isomers respectively, and this was explained in terms of what can be called “intermolecular competition theory ”. The steric interactions on the way to the two transition states for the elimination with retention were suggested to govern the competition between the two processes. On the way to the transition state starting from the zwitterion derived from the cis isomer (116c) there are only (H, H) interactions, compared to (H, ArS02) interactions for the transition state derived from the zwitterion formed from the trans isomer (116d). Moreover, (116c) may also be favoured by electrostatic interaction between the positive nitrogen and the negatively polarized ArSOz group, while in (116d)the two groups are far away. Since the protonation rates are expected to be similar, the lower addition/substitution ratio for the cis isomer reflects a relatively shorter-lived carbanion.

ArOzS - 8 --&--H

ArOig --&--H

H

ArOzS

H

(116c)

SOzAr

(116d)

Substitution with nucleophiles having P or As at the nucleophilic centre should show in principle a similar behaviour as amines. Indeed, only trans-2-p-toluenesulphonylethylenephosphonate (117b) was p-MeCeH4. S 0 2 . CH=CH

.S02.CeH4Me-p + P(0Me)S

+

p-Mec6H.1. SO2 .CH-CH.

S02. CeH4Me-p +

I

+P(0Me)a (117a)

p-MeCeH4SOzCH=CHP(O)(OMe)2 (117b)

obtained from either cis- or trans-1,2-di-p-toluenesulphonylethylene and trimethyl phosphite, even if the reaction was conducted at 30” (Meek and Fowler, 1968). This was explained by suggesting that isomer-

-

NTJCLEOPHILIC VINYLIC SUBSTITUTION

59

ization may occur by reversible addition of methyl phosphite to the intermediate (117a). Triethyl phosphite (Kataev et al., 1965)with transa-arylsulphonyl-/3-bromoethylene or trans-bis(p-bromovinyl) sulphone gives only the trans product, as expected for either mechanism. The cis-olefinswere not investigated. Both cis- and trans- 1,2-dichloroethylenesand cis- and trans-p-bromostyrenes gave complete retention with the anionic Ph2P- nucleophiles (Aguiar and Daigle, 1964, 1965a, 196513). Although the retention with the dichloroethylenes may result from elimination-addition (p. 78) the reaction with /?-bromostyreneshould be of the addition-elimination type. Retention was also observed for the reaction of diphenylarsenide ion Ph2As- with cis- and trans-/?-bromostyrenes (Aguiar and Archibald, 1967). Surprisingly, a-bromo-trans-stilbene gives, with the same nucleophile, the inverted substitution product a-diphenylarsino-cis-stilbene (Aguiar et al., 1967), but since it was established that the u-diphenylarsino-trans-stilbeneis isomerized to the cis isomer by heating in ethanol alone, it was suggested that either the initial reaction course is retention, or that elimination-addition is possible. It is noteworthy that the use of these strong nucleophiles results in the addition-elimination route for the unactivated halo-olefins. No details are available regarding the stereochemistry of the substitution by the neutral Ph,PH or Ph2AsH nucleophiles. Since the substitution products are stable to isomerization (except for the a-diphenylarsino-trans-stilbene),probably owing to the lower basicity of P and As compared to nitrogen, the two mechanistic explanations discussed are acceptable. h. Reaction with carbanions. Carbanions, being good carbon nucleophiles and strong bases, react by a multiplicity of mechanisms. While ,!I-halocrotononitriles react via the elimination-addition route (Boularand and VessiBre, 1967), methyl and phenyl magnesium bromides react with the p-chloroacrylic acids and esters to form mainly (81-99%) retained crotonic and cinnamic acid derivatives (Klein and Gafni, unpublished). The degree of retention is dependent on the solvent (ether or tetrahydrofuran) and on the presence of CuCl, as well as on the Grignard reagent used. The kinetically-controlled &/trans ratios are not always Ph\ C1,

H

,c=c

,COzH

‘X

PhMgBr

/COzH

/c=c H

+

Ph\

,c=c

H

\

H

PhMgBr ___j

/H

‘COzH

60

ZVI RAPPOPORT

known accurately, since addition compounds, e.g. (118),which are sometimes formed by the excess reagent, are probably produced from the primary products with different rates. With the less reactive diethylmalonate anion, Gidvani et al. (1932) found only retained products on reaction with the ethyl /3-chlorocrotonates. Carbanions are thus similar to the other anionic nucleophiles. i. Substitution in s y s t e m with two equal /3-leaving groups. Monosubstitution is possible in substrates with two identical /3-leavinggroups, e.g. for l,l-dimethylthio-2-carbethoxy-2-cyanoethylene (119) with aniline or ammonia (Gompper and Toepfl, 1962)or for j,/l-dichlorovinyl ketones with ethoxide or thiocyanate ions (Nesmeyanov et al., 1961). (MeS)&=C(CN>. COzEt -I-PhNHz (119)

4

PhNH. C(MeS)=C(CN).C0,Et

Truce and Kassinger (1958b) found only one product, which was assumed to be the cis isomer, from the reaction of p-tolylthiotrichloroethylene with p-toluenethiolate ion. It was shown later (Truce et al., 1965)that it is the trans isomer.

Analysis of the analogous reaction of the n-propylthio system (Truce et al., 1965) showed the formation of 94% of the trans isomer together with 6% of the cis isomer.

940,;

6%

I n t'hese systems, the conformer (120) formed by the nucleophilic attack, could give by 60' rotation either (121a) or (121b), both capable of eliminating the chloride ion. The eclipsing pairs on the way to (121a) and (121b) are (Cl, M) and (Cl, L), respectively. For complete retention, the geometry of the product would be determined by competition between these two interactions according to the competition theory, or by the relative cis effects in the conformers (121a)and (121b)themselves. For example, for RSCC1=CCl2 where Nu, L = R S and M=Cl, the interactions on the way to (121a) and (121b) are (Cl, C1) and (Cl, RS) respectively, and the competition theory predicts more cis isomer. On the other hand, if the cis effect determines the products, the two lower

N U O L E O P H I L I C V I N Y L I C SUBSTITUTION

61

(RS, C1) steric interactions compared to (RS, RS) and (Cl, C1)interactions should lead to more trans isomer, assuming that the RS interactions are largest. The preference for the trans isomer is in line with the latter

c’ez

M--

YU +NU __f

C1

M--

(121a)

=v::

c1

c1

(121b)

hypothesis and the excess interactions for the (PrS, PrS), (Cl, C1) pairs over two (PrS, C1) pairs is calculated to be 2 kcal mole-l. Although analysis in terms of short-lived carbanions fits the stereochemistry discussed up to now, the results should not be taken as indicative of short-lived ions. Thermodynamic control via long-lived carbanions will give the same results, as was actually suggested by Truce and coworkers. The proportion of isomers (trans/& dichloro = 73 :27)from thereaction of 1,1,2-trichloro-3,3,3-trifluoropropene with methoxide ion (Cook, 1967) also fits both the competition theory and thermodynamic control if the order of steric interactions is C1> CF, > OMe. CF3.CCl=CC12

+ MeO-

+

CF3\

/

,c=c

c1

C1

\OR

+

CF3,

/c=c

C1

/OR ‘C1

27%

730,h

On the other hand, the reactions of 4,4-dichloro-3-buten-2-one (122) with PhS- and PhO- ions give, respectively, 88% and 100% cis products

,c=c H

‘c1

8876 c1

McCO, (122)

H

/c=c

+

,c=c H 12%

OPh

\c1

\SPh

62

ZVI R A P P O P O R T

(Gudkova, 1962). This is unexpected on the basis of steric interactions and was ascribed to the operation of the elimination-addition route. The effect of size of the a-substituent was investigated by Tarrant et al. (1964) in the reaction of propynyl-lithium with substituted trifluoroethylenes. With X = C1 or Br, the transleis ratio of the product was 4 : 1 and 3 : 1 , while with larger X groups, such as CF, or CH=CH2, only trans isomers were formed. CF2=CFX +MeC=CLi

--f

MeC-C.CF=CFX

j. Retention of conjiguration in a n allylic ion. The short life-time of the intermediate could also be inferred from retention of configuration further away from the reaction site. Reaction of EtMgBr with a 80: 20 mixture of the two isomers of (123) which differed only in the geometry at the exocyclic double bond, gave an 80: 20 ratio of the corresponding substitution products (124). Similarly, a 95 :5 mixture of the corresponding ethers was formed from a 95 :5 mixture of (123) with ethoxide ion. While the configurations were not determined, it is highly probable that the configuration of the allylic double bond was retained in the substitution products (Park and McMurtry, 1967). The expulsion of the

fluoride ion is therefore faster than the isomerization of the intermediate allylic ion. k. Conclusions. The stereochemistry of the addition-elimination route accords in most cases with short-lived carbanionic intermediates in which the elimination of the leaving group is faster than internal rotation. Most of the carbanions are short-lived enough to give complete retention, while a few give also some inversion. I n these cases, the competition theory is not always able to predict the isomer ratio obtained. Where thermodynamically controlled products are suspected to be formed via long-lived carbanions, the possibility of isomerization, as well as the intervention of other mechanistic routes, should not be overlooked.

D. Reactivity in the Addition-Elimination Route Since Fond making is assumed to be the rate-determining step, it is expected that the relative reactivities of different activated olefins will be similar to those found in other nucleophilic reactions (e.g., additions)

NUCLEOPHILIC VINYLIC SUBSTITUTION

63

at carbon-carbon double bonds (Patai and Rappoport, 1964). This is indeed observed, at least qualitatively. The reactions are also, as expected, of the second order, first order in the nucleophile and first order in the olefin. The main factor which determines the reactivities is the ability of the a-substituent to spread the negative charge in the transition state. The large number of qualitative observations notwithstanding, quantitative data are limited. The rate constants, extrapolated to O'C, where necessary, for comparisons, and the corresponding activation parameters are collected in Table 7, on which the discussion below is based . 1. The eflect of the a-activating group

Data are available for a-arylsulphonyl, arylsulphoxide, aroyl, cyano, carbethoxy and nitroaryl activating groups, but in no case was the same nucleophile studied with all compounds. The comparisons are therefore indirect, and short series of reactivity orders are combined, with the assumption that the nucleophilicity order is only slightly substratedependent. The following comparisons are possible : A p-toluenesulphony1 group is 2.2-3.8 times more activating than the cyano group as judged from the reaction of the cis and trans isomers of a-substituted haloethylenes with piperidine. Phenylsulphonyl and benzoyl have similar activating effects on a trans ,&chlorine, but each is 2700 times more activating than two p-nitrophenyl groups in their reaction with ethoxide ion. From the reaction rates of di-n-butylamine and piperidine with a-benzoyl and a-propionyl-a-methyl-p-chloroethylenesand /I-chloro-a-methyl-a-p-toluenesulphonylethylene, and when allowance is made for the rate retarding effect of the p-methyl group in the latter compound, the relative reactivity order of benzoyl, propionyl and phenylsulphonyl is 30 :3 : 1. The cis- and trans-p-chloro-a-phenylsulphonylethylenes are 55 and 28-40 times more reactive than the a-sulphoxide analogues with PhSand MeO- ions, respectively. Although the corresponding arylthio derivatives were not investigated quantitatively, they are much less reactive. Comparison of cyano and carbethoxy groups is possible only for the crotonate system where the ,&methyl group may affect the relative reactivities. Ethylthiolate ion is 7-8 times more reactive with 8-chlorocrotononitriles than with ethyl p-chlorocrotonates, but phenylthiolate ion shows high configuration-dependence. The cis and the trans nitriles react faster than the corresponding esters by factors of 11 and 1-4, respectively. Introduction of an o-nitro group into the mildly reactive cis and transj3-bromo-p-nitrostyenesincreasesthe rate with PhS-ion 3400 and 41,500

T ~ L7 E

Rate Constants and Activation Parameters in the Addition-Elimination Route eis Substrate p-NO..CsH4.CH=CHBr p-NOa.CeH4.CHdHCl pNOa.CeH4.CH==CHBr 2,4-(NOs)aCsHa.CH=CHBr PhaC=CHF PhaWHCl (p-MeCeH4)nWHCl f m-MeOCsH4M===-CHCI (v-NOsC;H4jCPh=CHBr (p-MeOCeH4)cPh=CHcl f v-MeOCaH4EPh=CHCl &NO$. Ce6)d2=CHCl (p-NOa. CeHi)aC=CHBr ClCH4HCN MeCcldHCN MeCBMHCN MeCBdHCN MeCcl==CH.COaEt MeCcldMe. COsEt CHs=CCl .CHa .COsEt C H d B r CHI. COsEt PhCO C H 4 H C I p-MeCsH&O.C H S H C l p-clCeH1C0. C H d H C 1 p-BrCeH&O. C H S H C I PhCO CMe===CHF

. . . .

PhCO CMedHCl

Nucleophile

IPhSPhSMeOPhSMeOEtOpMeCeH4Sp-MeCeH4Sp-MeCsHdp-MeC6HBclBrEtOEtOPiperidine EtSPhSEtSPhSEtSWSEtSEtOPhSPhSEtOEtOEtOEtOPiperidine Piperidine

Ns-

Na-

Solvent Bu(0CHs. CHdrOH &OH MeOH MeOH MeOH MeOH EtOH DMF DMF DMF DMF DMF DMF EtOH EtOH MeOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH DMF 98% EtOH 98% DMF

tram

104kEa at00

AH*

AS*,,

1.9 x lo-^^ 013' 0345

23.9 17.2 18.3

-24 -17.8 -11.6

1150

13.2

-14.3

16.2 18.9 21.1

-240 -196 -170

0.46b 0037" 00025' 0~00012'

171,000' 4 6 x 10-l3' 17 x 10-6. 015' 01150 200 203 66.3' 1340 331f 24.3 055 0.142' 0.093' 17.7f 375f

35.3 18.5 18.6

13.5 147 16.1 19.9

104ka at 0" 5.3 X 10-'Oo 0.68" 1.26" 3.1 x lo-" 52,300 389

239,0OOc -456 5.4 x lo-"= 25.4 x 10-O' -12.5 -12.9 267 416 387' 13,700' 348f -20.5 56 -235 2.23 -21.5 -8.3 407O 97a 510" 167O 22.300" 47,100" 1.544 24.6"

AH+

AS+w

27.9 17.0 17.6 24.4 11.8 183

-16 -15.2 -1l.6 -2.8 -11.8 -7.1

326

13.9 15.4

101 98 102 10.1 12.3 16.2

Reference

Miller and Yonan, 1957 Marchese et al., 1968 Marchew et al., 1968 Marchew et d.,1968 Marchew et al., 1968 Blarchese et al., 1968 Silversmith and Smith, 1958 Beltrame et al.. 1967c Beltrame et d.,1967c Beltrame et al., 1 9 6 7 ~ Beltrame and Beltrame, 1968 Beltrame et d.,1966 -10d Beltrame et al., 1966 Beltrame et al., 1967b Beltrame et al., 1967b Scotti and Frazza, 1964 "heron, 1967 Theron, 1967 Theron, 1967 Theron, 1967 -16.5 Jones et al., 1960 Jones d al., 1960 -17.5 Jones et d.,1960 Jones et d., 1960 Theron, 1967 Theron, 1967 Kudryavtseva et al., 1963 -9.5 Kudryavbeva et al., 1963 -13.5 Kudryavtseva et al., 1963 -8.5 - 1 0 5 KudryavtSeva d al., 1963 Beltrame et al., 1968 Beltrame et al., 1968 -306 Beltrame d al., 1968 -11.1 Beltrame et al., 1968

.

PhCO CMe=CHCl

.

Piperidhe Piperidine n-ButNH

Ns-

MeO-

MeOH

PhCO C P h S H C l

N3-

EtCO .CMe===CHCl

NaPiperidine Piperidine Piperidme

yl:p"

Na-

NtPiperidine Piperidine PhCO.CH=CH.NOn' MeOH ~NO~.C~HI.SO.CH----CHCI PhSMeOPhSOa. C C I 4 H C I PhSMeOPhSOs.CH4HCI PhS-

.

PhSOr CH==CHCI

EtOH

0.0880

0.46' 360 40 2800 230

870 100 42,000 690 2000 20'

10.1 8.8

168 18.4 12.6 11.0 12.2 12.9 162 11.2 102 16.4

690

45.5'

180

105

6.3 42

3.4 52.5

PhS-

4820 43'

MiO-

ea. 26,000 ea. 500,000

1540 51' 88 303 3.0 54 400 670 4250

Cyclohexylamine MeOH MeOH n-BunNH PhSOr.CH4HBr

15.4' 32.50 7.34' 0.0170 0.67O 1.26' 6.7" 1.44' 03' 1.1' 016'

DMF

MeOH 98% EtOlf 98% D m EtOH DMF EtOH 94% EtOH-4y: DMF 98% DMF 96%EtOH-4%DMF DMJ? MeOH' MeOH MeOH MeOH XeOH MeOH MeOH

MeOH MeOH MeOH EtOH EtOCyclohexylamine MeOH MeOH n-BuaNH MeOH PhsMeOH p-MeCsH& EtOH p-MeCsH4SMeOH PhCHsSMeOH NsMeOH MeO-

133 125 1090 2000 9.0' 45

16.4

-1

14.5' 64

163

EtOH

3100

21.6

+19

248

15.2

N.-

EtO-9

12.5 12.0

-16.5 -17.5

14.1 141

ca. 10,000

Beltrame et al., 1968 Beltrame et d.,1968 Beltrame ~t al., 1968 Beltrame el al., 1968 -23 Beltrame el al., 1968 -10 -30 Baltrame et al., 1968 Beltrame et al., 1968 -32.7 Beltrame et al., 1968 -31.2 Beltrame el al., 1968 -33.1 Beltrame el al., 1968 -17.1 -39.5 Beltrame et al., 1968 Beltrame et al., 1968 -44.4 Nesmeyanov el at., 1966 Modem. 1958 Modena, 1958 Modena, 1958 Modena, 1958 Modena and Todesco, 1959 Modena and Todesco, 1959; Campagni et d.,1960 Maioli and Modena, 1959; Campagni el al., 1960 Campagni el al., 1960 Modena el al., 1959; Campagni et d.,1960 Campagni et al., 1960 Campagni et al., 1960 Campagni et al., 1960 Campagni et al., 1960 Campagni et al., 1960 Campagni et al., 1960 -13 Modem and Todesco, 1959 -12 Modena and Todesco, 1959 Modena and Todesco, 1958 Modem and Todesco, 1959 Modem and Todesco, 1959 -8.5 DiNunno et al.. 1966; Maioli and Modena, 1959 -9.5 Maioli and Modena, 1959 -342 -376

TABLE7 (continued) cia 104kz atO" Substrate p-MeCsHa. SOa .C H 4 H C 1

Nucleophile

MeOH MeOH MeOH MeOH p-MeCsH4. S O a . C H 4 H B r MeOH N3MeOH MeOCsclohex slamine MeOH MeOH nIBuzNH MeOH pClCsH4.SOa.CHdHCl PhSMeOH N3MeOMeOH Cvclohexvlamine MeOH MeOH nIBulNH MeOH m-ClCaH4.SOa.CH==CHCl PhSMeOH N3MeOH .MeOCyclohexylamine MeOH MeOH n-BuzNH MeOH 9-NOz.CsHa.SOz.CH==CHCl PhSMeOH N3MeOH MeOCyelohexylamine MeOH n-BuzNH MeOH MeOH p-NOz.CeHa.SOz.CH.=CHBr N3Cyclohexylamine MeOH MeOH n-BusNH MeOH pMeCsH4. SOZ C M d H C I PhSMeOMeOH MeOH n-BuzNH p N O a . C s H 4 . S O a . C M d H C I PhSMeOH MeOMeOH Cyclohexylamine MeOH MeOH n-BuzNH MeOH p-NOa.CsH4. S O n . C M e d H B r PhSMeOH MeO-

.

Piperidine Cyclohexylamine n-BuzNH PhS-

AE*

trans &*as

104ka at^"

AH*

AS*z5

Reference

Solvent 760 465 23.8 2480 23.1' 17,800 84.1 84.3 6960 5.4 430 17.3 92.4

48,000 53.4 2800 87.8 648 1550' 3360 710 1.73" 0155' 00155' 178a 2.7" 0.13" 0.460 4123.2'

129 11.6

-26.0 -27.5

142 194 12.0 11.1

-21.5 +6.5 -26.5 -26.5

13.8

-17.5

10.9

-27.5

15.9 17.5 14.5 14.1 18% 14.7 132 152 17.3

-17

-16

-31.5 -13 -6 -26.5 -29.5 - 8.5 -11

600 2.30 28.5 864 30.0' 53.5 2.2 30.6 2430 7.0 253 7.3 112 3700 145' 405 93%' 190 23,000 71.0 1680 386 658 1560' 38.8 553 0.66" 0.25' 0.0116" 533= 4.6' 0.049" 0.266° 130" 3.0'

12.6 12.1

-28.5 -25.5

15.1 154 12.2 11.3

-18 -8.0 -27.5 -25.5

14s

-13.5

11.3

-27.5

16.8 14.7 14.6 15.3 16.2 15.5 14.3 14.9 17.9

-15.5 -25.5 -31.5 -12.5 -14 -25.5 -24.5 -12 -8.5

Modeua et al., 1959 Modena et al., 1959 Modena et al., 1959 Campagni e l al., 1960 Campagni et al., 1960 Campagni et al., 1960 Campagni et al., 1960 Campagni et al., 1960 Modena and Todesco, 1959 Modena and Todesco, 1959 Maioli and Modena, 1959 Modena et al., 1959 Modena et at., 1959 Modena and Todesco, 1959 Modena and Todesco, 1959 Maioli and Modena, 1959 Modena et al., 1959 Modeua et al., 1959 Modena and Todesco, 1959 Modena and Todesco, 1959 Modena, 1958 Modena et al., 1959 Modena et al., 1959 Campagni et al., 1960 Campagni e l al., 1960 Campagni et al., 1960 Modena et al., 1960 Modena et al., 1960 Modena et al., 1960 Modena et al., 1960 Modena et al., 1960 Modena et al., 1960 Modena et al., 1960 Modena et at., 1960 Modena et al., 1960

MeOH MeOH MeOH EtOH MeOH p-MeC6Hr. SOa C H 4 M e B r MeOH MeOH MeOH MeOH p-NO2 ,CeH4. SOa .CH=CMeCl PhSMeONeOH Cyclohexylamine MeOH n-BuaNH MeOH p-NOa.CaH4. SOa.CH=CMeBr PhSMeOH MeOMeOH Cyclohexylamine MeOH u-BuzNH MeOH p-MeCaHa.SOa.CH=CMeCl

.

a

Cvclohexvlamine UIBU~NH MeOEtOPhsMeOCvclohexvlamine nIBuaNH

Extrapolated value.

* A t 100".

At 24O At 180'. A t 186'. f A t 25". Reacts probably via elimination-addition. h A t 30° Nitro is the leaving group. 9 Contains 0.0024 P acetate buffer. C

d

'

0.23" 057" 21 698 7.7 7420 58 30 141 719 7.7 4.5 342 78,500 2100 1050

14.1 146 19.4 184

-28.5 -24.5 -1 +8

0.076' 0.20'

14.1 14.7

-34.5 -25.5

Modena et al., 1960 Modena et al., 1960 DiNunno et al., 1966 DiNunno el al., 1966 Maioli et al., 1960 Maioli et al., 1960 Maioli el al., 1960 Maioli et al., 1960 Maioli et al., 1960 Maioli et al., 1960 Maioli et al., 1960 Maioli et al., 1960 Maioli et al., 1960 Maioli el al., 1960 Maioli et al., 1960 Maioli el al., 1960

68

Z V I RAPPOPORT

times, respectively and 12,500 times for the reaction of the trans isomer with MeO-. Judging by this rate increase, the 2,4-dinitrophenyl group is even more activating than p-nitrophenylsulphonyl. It is the strongest activating group known for which there are stereochemical data for the addition-elimination route. The combined order of activating ability of or-substituents is : 2,4-(NOz)CaHs > PhCO > EtCO > PhSOz > CN > COzEt > PhSO > p-NOzCaHc > PhS

> C1

where the PhSO and the CO,Et groups may exchange places. The introduction of an a-chlorine as a second activating group into /3-chloro-rr-phenylsulphonylethylenehas only small effect on the reactivity. With MeO- ion the rate increases 2.3- to 3.8-fold, and with PhS- ion 4-to 21-fold. The relative activating ability of the halogens was discussed in Section (IIIB,3). The requirement for a positive ,&carbon is also reflected in Table 8, which summarizes the known Hammett p values. All these are positive, with the least reactive system showing the highest response to substituent change. The p value for the diarylhaloethylene-ethoxideion reaction is the highest, followed by that for the reaction with the more reactive p-toluenethiolate ion. I n the a-arylsulphonyl-B-chloroethylene series, the highest values are again for the slow azide reaction, but TABLE8 Hammett's p values for Nucleophilic Vinylic Substitutions P

System ArzC=CHCl

Nucleophile EtO-

Solvent, t"C

trans

cis

EtOH, 120

3.38

EtOH, 50

4.17

3.4

hzC=CHCl

p-MeCaH&3-

DMF, 50

ArSOz. CH=CHCl

n-BuzNH

MeOH, 0

1.50

1.48

h S O z . CH=CHCl

Cyclohexylamine

MeOH, 0

1.22

1-21

ArSOz .CH=CHCI

NI

MeOH. 25

1.84

1.85

ArSOa .CH=CHCl

PhS-

MeOH, 0

1.60

1.84

ArSOz .CH=CHCI

MeO-

MeOH, 0

1.56

1.60

Reference Beltrame et al., 1967b Beltrame et al., 1967b Beltrame et al., 1967c Modena et al., 1959 Modena et al., 1959 Modena and Todesco, 1959 Modena and Todesco, 1969 Maioli and Modena, 1959

NUCLEOPHILIC VINYLIC SUBSTITUTION

69

values with other nucleophiles are not much different. The similarity of the p values for cis-trans series is noteworthy. The reactivity order of the a-aroyl-8-chloroethylene-ethoxideion reaction does not follow the Hammett equation (Kudryavtseva et al., 1963),since the activating order of p-substituents is p-C1> H >p-Br > p-Me. The anomalous position of the p-Br derivative, which should be more reactive than the unsubstituted one, was ascribed to the operation of the + M effect of the bromine atom, which is stronger than its usual --I effect. Only small differences are found between pairs of cis-tram isomers reacting via the addition-elimination route (Table 7) while high differences are usually associated with the elimination-addition routes. The ktfane/keis ratio of ca. 50 at 0" for the 8-brorno-2,4-dinitrostyrene-PhSreaction is unusually high compared to the normal ratios (0.3-4)with this nucleophile. Decreased reactivity of the cis isomer, resulting from steric interactions between the nitro group and the bromine, which force the activating aryl group out of the plane of the double bond, may be responsible. The PhSO,C(Cl) =CHCl-PhS- reaction also shows a large kd8/ktr,,,, value of 15, but the value is only 3 for the smaller MeO- ion. 2. The effectof the @-activatinggroup The effect of the 8-activating group was discussed in relation to the element effects. It was shown recently (Theron, 1967)that in its reaction with PhS' ion the chlorovinylacetic ester (125) is three-times more reactive, and 1.4 times less reactive than the cis- and trans-ethyl 8-chlorocrotonates,respectively. This is remarkable, since the activating

CHz=CCl-CHZCO,Et (125) group is attached to the 8-position, and separated &om the reaction site by one methylene group. 3. The effect of a- and 8-methyl groups A methyl group attached to the double bond should decrease the rate of the nucleophilic attack by increasing the electron density and the steric interactions at the double bond. I n addition, an a-methyl group should decrease the overall rate even for highly basic nucleophiles, by blocking the elimination-addition route. Substituent effects in a-aqlsulphonyl-8-haloethylenesbear out this prediction. The rate retardation by an a-methyl group, kH/kMeis more pronounced for the less reactive p-methyl derivative than for the p-nitro derivative. For several nucleophiles, kH/kMe values for the former derivative are higher by one order of

70

Z V I RAPPOPORT

magnitude. Anionic nucleophiles (MeO- and PhS-) show lower retardation (kH/kMeare 27-52 for the p-nitro derivatives and 255-630 for the p-methyl derivatives) than di-n-butylamine (where the corresponding values are 166-240 and 1530-2460). The higher values for thep-methyl derivative are in line with the higher response to accelerating effects for the less reactive systems. a-Methylation of ethyl /?-chlorocrotonatealso causes a 170-foldrate decrease with EtS- ion. The effect of /?-methyl groups was investigated only for the &-aarylsulphonyl-/3-bromo-or /?-chloro-ethylenes. The 2.4- to 3-9-foldrate decrease with MeO- ion, as well as the 1.3- to 3.2-fold decrease for /?bromo-a-~-nitrobenzenesulphonylethylene-di-n-butylamineand cyclohexylamine reactions, may point to a contribution of the eliminationaddition route with these nucleophiles. When the elimination becomes more difficult, either for thep-methyl derivative or with a chlorine leaving group, a /?-methylgroup decreases the substitution rate 20- to 84-fold with the same amines. With PhS- ion, for which other substitution routes are less probable, the rate retardation is higher (322- to 3100fold). An a-phenyl group is expected to increase the rate owing to its chargespreading ability. However, introduction of a-phenyl into the a-benzoyl/!-chloroethylene system deactivates more than an cr-methyl group, the effect being higher for reaction with azide ion (kMe/kPh= 37-90) than for piperidine (kMe/kPh= 5-12). This is probably due to a reduced planarity of the benzoyl group with the double bond as a result of the steric effect of the phenyl group. 4. The relative reactivities of the nucleophiles Of the many nucleophiles which have been used in vinylic substitutions, the relative reactivities of only a few are known. A nucleophilicity is given in Table 9. order towards /?-chloro-a-p-toluenesulphonylethylene From Table 7 it could be inferred that the same order although with somewhat different relative reactivities exists for systems in which bromine is the leaving group, or which have a- or /!-methyl substituents, or different p-substituents. The relative reactivities of cyclohexylamine and azide ions are sometimes reversed for other systems. Since approximately half of the nucleophiles are basic enough to follow the eliminationaddition route when possible, comparisons should always be made for reactions with activated olefins with cis relationship of the leaving group and the a-hydrogen. As seen from Table 9, thio nucleophiles are the best ones, their reactivity being increased by electron-donating substituents. The less basic cyclohexylamine is also the least reactive of the amines. The relative reactivities of di-n-butylamine and piperidine are the

NUCLEOPHILIC VINYLIC SUBSTITUTION

71

reverse of their basicities. This may result from a lower steric interaction in the transition state of the substitution by the cyclic amine. The reactivity of the halide ions could not be evaluated directly since they have not been studied with the same substrate. However,p-toluenethiolate ion is nine orders of magnitude more reactive than chloride ion towards 2-chloro-1,l-diarylethylenes in dimethylformamide. Although comparison may not be justified (see below), a similar reactivity ratio exists for the reactions of /3-bromo-p-nitrostyrene with iodide ion in butyl cellosolve and thiophenoxide ion in methanol. Bromide ion is 0.6 times as reactive as chloride ion towards l-anisyl-l-phenyl-2chloroethylene. These relative reactivities of the halide ions should be regarded only as rough estimates. Their very low reactivity is also shown by the chloride exchange in ethyl /3-chlorocrotonate, which is at least los times slower than the substitution by thioethoxide ion (Jones et al., 1960) while trichloroethylene does not exchange at all even at 245" (Bantysh et al., 1962). TABLE9 Relat'iveNucleophilicities Towards trans-p-MeC~H4SO2CH=CHCl in MeOH at 0'

Nucleophile

Relative nucleophilicity

C1-, Br-, I-

ca. 10-7"

N,

0-63b 1.0 12.4 28 174 260 290 4530

Cyclohexylamine n-BuzNH MeOPhSPiperidine p-MeCsH4SPhCHzS-

Reference Miller and Yonan, 1957; Beltrame et al., 1966, 1967c Modena and Todesco, 1959 Modena et al., 1959 Modena et al., 1959 DiNunno et al., 1966 Modena and Todesco, 1959 Modena el al., 1959 Modena and Todesco, 1959 Modena and Todesco, 1959

a Based on relative reactivities towards diarylchloroethylenes and 8-bromo-p-nitrostyrenes. Calculated by taking E,= 15 kcal mole-'.

It is noteworthy that the PhS-/MeO-rate ratios are not much different for the unreactive /?-bromo-p-nitrostyrene and its very reactive 2,4dinitro analogue, being 4000 and 13,000, respectively. The relative reactivities of Table 9 differ from those towards saturated carbon atom, as measured by the n-values of the Swain-Scott equation,

Z V I RAPPOPORT

72

but the order is similar to that found for nucleophilic aromatic substitution reactions (Bunnett, 1963). That a relative nucleophilicity scale based on one solvent and one substrate may not be applicable for different conditions and systems is clearly demonstrated by the work of Beltrame et al. (1968). While the lcpiperidine/kN;ratio towards the substrate of Table 9 is approximately 410 at 0" in methanol, the ratios for ethanol kpiperidine(EtOH)/ kN$8% are 74, 10 and 0.55 towards a-benzoyl-/3-chlorostyrene (125a), 1-chloro-2-benzoylpropene(125b) and 1-acetyl-2-chlorocyclopentene (125c),respectively. Since the change from ethanol to 98% aqueous ethanol will only slightly change the polarity of the solvent, this amounts to areversal of reactivity of the two nucleophiles, and to a change of three orders of magnitude in the relative reactivity. PhC==CHCl

MeC=CHCl

I

I

COPh

COPh

(125a)

(125b)

(,l25c)

The ICpiperidine(DMF)lkN~~8% DMF) ratios for (125a),(125b)and (125c) at 0' are 10,1.3 and 0.08, respectively, i.e. decrease in the same order and to about the same degree as the ratios in ethanol. While the change in the ratio in dimethylformamide may be accounted for by the enhancement of reactivity in the (slightly aqueous) dipolar aprotic solvent (Parker, 1965),the occurrence of the same trend in ethanol, and especially the dependence on the structure of the attacked substrate, points to the need for caution in the construction of nucleophilicity scales. .

A

5 . Activation, parameters

The activation energies for the a-arylsulphonyl and a-aroyl or a-acyl8-haloethylenes are in the 10-18 kcal mole-I region. The differences between cis and trans isomers are usually small (1-2 kcal mole-I). Higher differences (up t o 4 kcal mole-l) were observed for the very unreactive systems of haloarylethylenes, which also showed the higher activation energies. The differences between cis and traw isomers with alkoxide ions, as well as the relatively high value for ethyl /3-chloro-amethylcrotonate probably indicate the intervention of a$- and p,yelimination-addition routes. Solvent effects on the activation energies are observed in the reactions of carbonyl-activated haloethylenes. The values for the reaction with piperidine are smaller (by ca. 1 kcal mole-l) in dimethylformamide

WUCLEOPHILIC VINYLIC SUBSTITUTION

73

compared to ethanol, while those for the azide ion reactions are higher (by 2-4 kcal mole-l). The activation entropies are mostly negative, as expected for reactions in which one species is formed from two. The differences between the values for the isomers are generally low. The most interesting feature of these values is the large increase in the activation entropy when the azide ion reaction is conducted in dimethylformamide instead of in ethanol.

E. Substitution with Rearrangement (The “Abnormal” Substitution) When the leaving and the activating groups are attached to the same carbon atom, the activation of the a-carbon is usually too low to enable substitution .via addition-elimination. Nucleophilic addition of the nucleophile and a proton is however possible, the nucleophile being attached to the /3-carbon. A hydrogen atom bonded to this carbon may then be eliminated with the a-leaving group, forming a rearranged product in which the nucleophile is attached to the /3- rather than to the a-carbon atom (equation 8). Other reaction courses, e.g. cyclizations, RCH=CXY+NuH + RCHNU-CHXY

- HX + RCNUECHY

(8)

followed the a,/3-adduct formation from active methylene compounds (Sopova et al., 1963, 1964). and 1-bromo-1-nitro-1-olefins The intermediate adduct is generally stable enough so that spontaneous dehydrohalogenation does not take place. For example, the 3-(arylthio)-2-halonitriles which are obtained from thiols and a-chloroacrylonitrile, form rearranged products only in the presence of dehydrohalogenating base (Birum and Heininger, 1957; Heininger and Birum, 1965). CHz=C(CX)Cl+ArSH

base +ArSCH2.CH(CN)Cl d ArSCH=CHCN

An interesting system is that where the activating group itself is capable of leaving as a carbanionic entity. Rybinskaya et al. (1963) found that both “normal substitution product ”, 1-benzoyl-2-methoxyethylene (126) and the “abnormal product ”, l-benzoyl-l-methoxyethylene (127) are formed from the reaction of 1-benzoyl-2-nitroethylene with methanolic methoxide ion. The relative electrophilicities of the carbon carrying the nitro group and that carrying the benzoyl group are obtained by measuring the rates of formation of (126) and (127). I n acetate buffers, 30% of the attack is u to the nitro group, and 70% a to the benzoyl group. An a,p-adduct is formed in the latter case, decomposing subsequently to (127). While one of the product-forming steps leading to (127) is slow, its amount is nevertheless determined in the

74

ZVI RAPPOPORT

primary addition step which is thought to be irreversible. The slow step is the ionization of the proton a to the benzoyl group, and it is followed by rapid loss of NO, (Scheme6). At 25", 106kvaluesare kl= 605, k2 = 275 and k3= 5-4 (Nesmeyanov et aZ., 1966). The similar activation energies associated with kl and k, suggest that bond formation to the nucleophile is the rate-determining step for both. PhCO .CH=CHNO2 -tMeO-/MeOH

PhCO . C(OMe)-CH2N02

PhCO . CH=CHOMe (126)

1

- NOa-

.

PhCO C(OMe)=CHZ (127)

SCHEME 6

F. Summary Owing to the emphasis in our treatment on criteria rather than on individual reactions, the various arguments that a specific reaction series followed the addition-elimination route were spread among the different sections. It is worthwhile to summarize that the use of stereochemical, isotope exchange, kinetics and element effects show that the a-arylsulphonyl-/3-haloethylenes(Modena et aZ.), the /I-halo-a-nitrostyrenes (Modena et aZ.,) the a-aroyl-P-haloethylenes (Montanari et d.) and the /3-halocrotonic esters and nitriles (Theron, 1967) systems react with thioanions via this route. Use of some of these criteria together show its operation for other reaction systems.

IV. THEELIMINATION-ADDITION ROUTES When a proton is available for expulsion in the vicinity of the leaving group, both may be eliminated. Consecutive addition of the nucleophile Nu and hydrogen to the elimination product finally yields a vinylic substitution product. These " elimination-addition " routes are the

N U C L E O P H I L I C V I N Y L I C SUBSTITUTION

75

a,/?-elimination-addition, forming an intermediate acetylene (equation 9), the /?,/?-elimination-addition forming an intermediate carbene (equation 10) and the /?,y-elimination-addition forming an intermediate allene (equation 11). - HX +NuH + RC=CY +RCNu=CHY

RCX=CHY

-

- HX

HCX===CHY 4 :C=CHY R'R2CH-CX=-CHY

- HX

RlRW=C=CHY

+ NuH HCNu=CHY + + NuH RlRZCH-CNu=CHY +

(9) (10) (11)

A. The a,/?-Elimination-Addition Route This is the most common of the elimination-addition processes. When the a-carbon carries both the activating group and an hydrogen, the acidity of the latter increases and when the nucleophile is basic enough and the leaving group is in a favourable geometry for elimination, HX is eliminated, forming the acetylene (128). Addition of the base B used in the elimination, or another nucleophile Nu-and a proton gives the substitution products (129) and (130).

Various criteria have been used to deduce the operation of this mechanism. Since some of them are dependent on comparison with the addition-elimination route, the competition between these two routes will be also discussed. (1) The nature of the attacked system. Unactivated systems, such as those having only the leaving group as a vinylic substituent, usually react via the elimination-addition route. With the increase in the activation, competition with other routes may become important. (2) The nature of the nucleophile. The elimination-addition route requires a strong base which is capable of abstracting the proton. Competition between attack at carbon and at hydrogen will occur if hydrogen and carbon basicities of the nucleophile are both high. The base and the nucleophile are not necessarily the same. A strong base present in the reaction mixture, e.g. RO-, may be responsible for the elimination, while a weaker one, which is a better nucleophile, e.g. RS-, may add preferentially to the acetylene. The elimination-addition route

76

Z V I RAPPOPORT

should be always considered for alkoxide ions and amines, but it may also operate for some of the more basic thioanions. (3) The product conjguration. No stereochemical relationship between the configuration of the starting olefin and that of the substitution product is expected if both isomers react by elimination-addition. The same acetylene is formed from both isomers, and the same product or mixture will be formed since the stereochemistry of the product is determined in the addition step. The stereochemistry of nucleophilic addition to acetylenes has recently been reviewed (Winterfeldt, 1967). Thioanions were found to give trans-addition, i.e. the nucleophile and the activating group are in cis positions in the product. The configuration of a cis starting material would therefore be retained in the substitution product (Truce, 1961; Stirling, 1964a). Alkoxide ions add in a transfashion to most systems (Miller, 1966; Winterfeldt, 1966; Eaton and

'*\ /c=c /y H

H '

base __j

HCzCY

RSH

RS\

/c=c

___f

H

/p

'H

Stubbs, 1967) but not always so (Winterfeldt et al., 1966; Harris, 1967; Theron, 1967). The addition of amines, which is dependent on the nature of the amine involved (e.g. Huisgen et al., 1967) was discussed in more detail on pp. 54-58. Sometimes the cis isomer reacts via elimination-addition (see (5) below) while the trans isomer reacts via addition-elimination. Since the configuration is retained in the latter route, either addition-elimination for both isomers, or elimination-addition for the cis and additionelimination for the trans isomer would show overall retention of configuration. (4) Isolation and study of the behaviour of the intermediate. Although a substituted acetylene is the intermediate in the elimination-addition route, its isolation is dependent on the relative rates of its formation and destruction by the nucleophilic addition. Acetylenes can sometimes be isolated as the main reaction products, but in other cases, they have only been detected spectroscopically, or they may be trapped if they are very reactive. Detection of acetylene does not always prove that it is a reaction intermediate. Since generalization regarding the stereochemistry of the nucleophilic addition to acetylenes may be misleading, the independent behaviour (stereochemistry of addition, rate of disappearance) of the alleged intermediate acetylene should be studied. I n favourable cases, these data enable quantitative dissection of the substitution process into its addition-elimination and elimination-addition components.

NUCLEOPHILIC VINYLIC SUBSTITUTION

77

(5) The con$guration of the starting olejn. The proton and the leaving group must be in trans positions for elimination. This is possible for the cis isomer (having cis leaving and activating groups) but not for the trans isomer. The cis isomer thus prefers the elimination-addition route, while the trans isomer mostly reacts via addition-elimination, even if the other conditions favour the elimination-addition. If both isomers react by the latter route, the easier trans elimination would predict high keis/kt,,, values. If they follow different routes, their relative reactivities are also expected to be different, and the cis isomer is usually the more reactive one. The difference will also be reflected in the activation parameters. In most cases the activation energy is higher for the elimination-addition route, but examples are known where the differences are small. (6) Element effects. The importance of bond-breaking in either ElcB or E2 processes, which are the ones expected to operate in the formation ratios for the elimination-addition, of acetylenes, predicts high kBr/kC1 (7) Isotope exchange and isotope effects. The vinylic hydrogen is lost and reintroduced from the solvent during the elimination-addition process. Incorporation of deuterium from deuteriated solvents is therefore expected. Depending on the elimination mechanism, hydrogen isotope effects would be also sometimes observed when RCX=CDY is compared with RCX=CHY. Several of the above criteria are usually used together in order to ascertain the reaction mechanism. The examples below will demonstrate their use, as well as the close relationship between the eliminationaddition and the addition-elimination routes. 1. Reactions of polyhabethylenes

The rule of trans addition of thio nucleophiles to acetylenes (Truce and Simms, 1956; Truce et al., 1960, 1961; Truce, 1961) and other criteria had been used by Truce and coworkers in their systematic study of the substitution routes of the chloroethylenes with p-toluenethiolate ion. The monosubstitution of vinyl bromide (Truce et nl., 195613)probably occurs via elimination-addition owing to the low reactivity of the halo-oleh. Acetylene is the only product formed with alkoxide ions or aniline. cis-Dichloroethylene (131), with a favourable geometry for trans elimination, gave cis-1,2-di-p-tolylthioethylene (135) in basic solution (Truce et ab., 1956a) while the trans isomer was unreactive in the same conditions. This difference, combined with the independence of the reaction rate of the thiolate concentration, suggested a slow primary

ZVI R A P P O P O R T

78

dehydrohalogenation. The high activation energy, 34 kcal mole-1 was indeed close to that of elimination by MeO- in methanol (Miller and Noyes, 1952). A fast trans-addition to the chloroacetylene (132) formed, (133). Indeed, independently should give cis-1-arylthio-2-chloroethylene prepared (132) gives (133) and (135) on reaction with arylthiolate ions in basic solution. It was also shown that (139), the trans isomer of (133), C’,

H

,c=c

,C’

Et0__f

ArS\

ArS-

HCsCCI

\H

__j

H

,c=c

ArSC-CH

HC1

__j

\H

+

(134)

ArS\ ,SAr ,C=C H H ‘ (135)

is not an intermediate, since it yields only 10% of (135) in conditions where (131) gives (135) quantitatively. The configuration of (135) and the necessity for a strong base during its formation from (133) indicate a second elimination-addition step via (134). Although 1,1-dichloroethylene (136) can undergo trans-elimination, its hydrogens are less acidic than those of the 1,2-isomer,which e.g., is able to form a mercury derivative of (132) with K2Hg14while (136) cannot. On the other hand, the electrophilicity of the p-carbon is increased by the combined effect of the two a-chlorines, and with p-toluenethiol both the addition product (137), and the “abnormal substitution product ” (139) are formed (Truce and Boudakian, 1956a). Formation of (139), rather than of its isomer (133), was ascribed to the tendency to decrease the steric interactions between large groups in the transition state for SAr

EtO-

ArS

H’

‘c=c

/

‘C1

H

NUCLEOPHILIC VINYLIC SUBSTITUTION

79

elimination (the “cis effect ”) (Curtin, 1954; Eliel, 1962). Since (139) has lower steric interactions than (133), the conformation for the elimination is probably (138). The requirement of a strong base for the further reaction of (139) and the formation of the cis-l,2-di-p-tolylthioethylene(135) indicate elimination-addition via (140), since the trans isomer should be formed (139) + ArSC=CH

--f

(135)

(140)

either from the c+adduct or from a short-lived carbanion. The (139) --f (140) reaction should be sluggish since it is a cis elimination, and the yields of (135) are correspondingly low in the usual conditions. Trichloroethylene (141), which combines the structural features of gives the trisubstituted product both 1,l- and cis-1,2-dichloroethylene, (145) by a multi-step reaction (Truce and Kassinger, 1958a). Since the formation of the monosubstitution product (143) requires the presence of base, and since the substitution product is a sterically hindered one, this stage is probably an elimination-addition. Additional evidence is the preparation of (143) from independently prepared (142), and the deuteriation of (141) in the presence of Ca(OD), (Leitch and Bernstein, 1950). The formation of the trisubstituted product (144) which was ascribed to an addition-elimination owing to the difficulty of dehydrobromination, and the trans configuration of (144), have already been discussed. The formation of (145) again requires strong base, and is again an elimination-addition.

ArSCHCl-CHClSAr

ArS\ __f

,c=c

.c1

/H

EtO__t

\SAr (144)

t-Butylthiolate ion gives parallel results to those with p-toluenethiolate ion, but the reaction with cis-1,2-dichloroethylene does not require an additional base, since the nucleophile is basic enough to effect dehydrohalogenation (Flynn et al., 1963). At high temperatures

80

ZVI RAPPOPORT

it is even sufficiently basic to cause cis-dehydrohalogenation of trans1,2-dichloroethylene,which is followed by the formation of cis-l,2-di-tbutylthioethylene. The reaction with sulphite ion follows, at least initially, a, similar course (Truce and Boudakian, 1956b), and other thiols react similarly (Parham and Heberling, 1955). Obviously, tetrachloroethylene (146) which is sufficiently active owing to the four chlorine atoms, could react only via the additionelimination route, and the trans-disubstituted product (149) is formed by two such consecutive steps (Truce and Kassinger, 1958b; Truce et al., 1965). It is interesting that the monothioaryl derivative (147) reacts only in the presence of base. Since elimination-addition is impossible, this was taken as indication that the base is required for the formation of the carbanion (148) which should be the reaction intermediate in this case. The tetrasubstituted product is obtained under drastic conditions only. c12c=cc12

AIS-

%

,c=c c1

(146)

4

ArSCCl-CC12SAr

‘c1

-

(147)

ArS ,c1 \c=c \SAr cl/

ArS-

sealed tube

(ArS)2C=C(SAr)2

That the substitution mechanism depends on the nature of the nucleophile is shown by the formation of the ketene acetals (151) from the reaction of vinylidene chloride with alkoxide ions. It was suggested that two consecutive eliminations-additions take place, and that in both cases the alkoxide attacks the acetylene at the substituted carbon (Kuryla and Leis, 1964). Since chloroacetylene (132) is also an interHzC=CC12 (136)

RO-

ROH

RO---+

H W C l M H2C=C(OR)CI (132)

(150)

HC=COR

ROH __f

H&=C(OR)z (151)

mediate in the substitution of cis-l,2-dichloroethylene, it is expected to give the same substitution product. Indeed, reaction of /3-methoxygave the ethoxide ion with 1,l-, cis-l,2- and trans-l,2-dichloroethylenes same /3-alkoxyethyl acetal (152) (KuryIa, 1965). Since l-bromo-2H2C=CC12 or cis- and trans-ClCH=CHCl

.

MeOCHa CHZO-

HeC=C(OCHz. CH20Mo)z (152)

NUCLEOPHILIC VINYLIC SUBSTITUTION

81

ethoxyethylene (153, X = Br) gives the mixed acetal(l54) with the same nucleophile, the intermediate in the alkoxide reaction is probably (153, X = C1) rather than (150), and the (136) -+ (151) reaction involves both routes (IV) and (V) of Scheme 1. XCH-CHOEt X=Br

+MeOCHz. CH20- + CHZ=C(OEt)OCHz. CHaOMe

(154)

(153)

2. Reactions of cyclic halo-oleJins The formation of a symmetrical acetylenic intermediate which is too reactive to be isolated has been investigated by studying the scrambling of the two carbon atoms in the substitution products. The l-halocycloalkenes would form the highly strained and reactive cycloalkynes by elimination. 1-Phenylcyclohexene is formed from 1-chlorocyclohexene and phenyllithium (Wittig and Harborth, 1944) and the corresponding labelled compound was therefore investigated (Scardiglia and Roberts, 1957; Montgomery et al., 1965). (155a) Reaction of equimolar mixture of l-chlorocyclohexene-6-C14 and l-chlorocyclohexene-2-C14(155b) with phenyllithium in ether at 150" gave 1-phenylcyclohexenewhich retained 23% of the radioactivity in l-phenylcyclohexene-1-C14 (157d). Since, in the absence of isotope effects, the symmetrical intermediate cyclohexynes (156a) and (156b) have equal probability to react at either carbon, each of the four substituted cyclohexenes (157a-157d) should contain one-quarter of the activity.

*)(

C1

(155a)

$. - [0' o'] C1

+

PhLi

(155b)

PhLi

__f

+

(156a)

yJ*

Ph

(157a)

(156b) Ph

+

()*+ (157b)

6*+ (jp* Ph

(157c)

(157d)

A similar investigation of l-chlorocyclopentene-1-C14 (158) (Scardiglia and Roberts, 1957; Montgomery et al., 1965)gave at the same conditions 1-phenylcyclopentenewith 48-9%, 36.2% and 14.9% of the label at the 1,2, and the 5 positions, respectively. This distribution fits a symmetrical

82

ZVI RAPPOPORT

cyclopentyne intermediate (159) since it was assumed that (160c) is formed by phenyllithium-promoted rearrangement of its initiallyformed allylic isomer (160b). Ph

Ph

Ph

(16Oa)

(160b)

(160c)

Only (157b), ( 1 5 7 ~ )and (160a) could be formed via an exclusive addition-elimination route, and this route, followed by rearrangement, should be less favourable than the or#-elimination-addition route which quantitatively explains the product ratios. The alternative /3,y-elimination-additionroute, forming the cycloallenic intermediate (161, n = 2 , 3) could not be dismissed, since the equilibrium between a cycloallene and the corresponding cycloalkyne

favours the former for (161, n=6-9) (Moore and Ward, 1963). The products from 1-chlorocyclopentene could be equally accounted for if attack on (161) at the central carbon gave half of the product, the other half being formed by reaction at the terminal positions followed by allylic rearrangement. Roberts and coworkers argued against such an intermediate by citing the selectivity of arynes to nucleophiles,assuming that cycloallenes too would show selectivity. The similar ratios of products formed by attack at the central to the terminal positions of the alleged cycloallenic intermediates for both the chlorocyclopentene and cyclohexene series are in contrast to this expected selectivity. That 1,2-cyclohexadiene (161, n = 3) is formed in a related system, from the reaction of 1-bromocyclohexene with potassium t-butoxide in dimethyl sulphoxide, is shown by trapping it by the highly reactive 1,3-diphenylisobenzofuran(162). The Diels-Alder adduct (163), differs from that, of cyclohexyne (164) which was obtained from 1,2-dibromocyclohexene and Mg in the presence of (162). The product (164) did not isomerize to (163) (Wittig and Fritze, 1966). Similarly, internal substitution in 2-halo-3-(2-hydroxyethoxy)-cyclohexene (165), catalysed by t-BuO- ion (Bottini and Schear, 1965) pro-

83

NUCLEOPHILIC VINYLIC SUBSTITUTION

do

(161, n=3)

Ph (163)

ceeds via the substituted cyclohexadiene (166). It is noteworthy that the product (167) is an “abnormal substitution product ”, formed by route (IX) of Scheme 1.

Additional evidence for the chloroacetylenic intermediate in the phenyllithium reaction is therefore necessary. Montgomery and Applegate (1967) have found that 1-chloro-2-methylcyclopenteneand 1-chloro-2-methylcyclohexene(168, n = 2, 3), which are incapable of forming cycloacetylenes,gave no substitution product, although formation of a cycloallenic intermediate was not prohibited. The isomeric 2-chloro-3-methylcycloalkenes (169, n = 2, 3) which can form a cycloacetylenic intermediate, gave about equal amounts of the two substitu(CH2)n-CHz

I

MeC=CCl

1

(168)

(CHz)n-CHMe

I HC-CCl

(169)

I

PhLi

- I

(CH2)n-CHMe

I

C

C(170)

(CH&-CHMe

- I

HC= (171)

(CHz),,-CHMe

I + PhC= I CPh

(172)

I

CH

84

ZVI RAPPOPORT

bion products, (171) and (172), corresponding to the addition of phenyllithium to either acetylenic carbon of (170). Moreover, when the three abstractable protons of l-chlorocycloalkenes are replaced by deuterons (173, n = 2, 3,4) the coupling product contains 1-84and 0-14,1.93and 0.82 and 1-96and 0.17 allylic and vinylic cleuterons for n = 2, n = 3 and n = 4, respectively. The corresponding isotope effects are 3.6, 5.3 and 7.2. Whereas the isotope effects are

(rT2 Y

DC= a

CCI B

(173)

consistent with elimination with a considerable C-H bond cleavage, the nearly complete retention of allylic deuterons excludes a /l,y elimination. However, formation of (170) would require the complete loss of the vinylic deuteron, which is not the case. The small amount of deuterium for n = 2 and n = 4 was ascribed to allylic isomerization products of the initially formed y,y-dideuteriated products, while the higher amount for n = 3 was ascribed to the protonation of the organolithium intermediate by another (173) molecule. The symmetrical nature of the intermediate is evidenced from the deuteron magnetic resonance spectra of the products (Montgomeryet al., 1967). The spectrum of that derived from the reaction of (173, n = 4) showed two types of saturated deuterons of equal intensity, fitting equal amounts of (175) and (176), and making the route (173) + (174) + (175) + (176) very likely.

The products from the lithium piperidide-catalysed substitution of (173, n = 3) by phenyllithium are also compatible with the above picture. Routes (IV) and (V) of Scheme 1 therefore operate together for the cyclic halo-olefins. An unsymmetrical acetylenic intermediate is formed from 3-bromo-2cyclooctenone (177) which gave on reaction with base in methanol-d a substituted methoxyether (179) with over 90% vinylic deuterium (Eaton and Stubbs, 1967). The intermediate was shown to be 2-cyclo-

NUCLEOPHILIC VINYLIC SUBSTITUTION

86

octynone (178) rather than 2,3-~yclooctadienone,by trapping it with (162).

In conclusion, the differences in the nature of the cyclic intermediates seems to be dependent on the base system, the leaving group, the relative reactivity and the rate of interconversion of the cycloallenic and cycloacetylenic intermediates. 3. Reactions of activated systems The elimination-addition routes can be traced by exchange of a labelled vinylic hydrogen in the elimination step, or by incorporation of deuterium from the solvent in the addition step. Whereas the absence of exchange argues generally against the operation of these routes, its occurrence is not unequivocal proof for them. Both cis and trans a-deuteriated #3-halo-cc-p-toluenesulphonylethylenes( 11-a-D) gave deuteriated phenyl thioethers with PhS- ion, whilst the ethers from the reaction with MeO- ion contained no deuterium (equation 12). I n MeOD, the ,%methyl derivatives (12) gave undeuteriated product with PhS- ion, and deuteriated ether with MeO- ion (equation 13), while the a-methyl derivative (13)gave no incorporation from the solvent (equation 14). The results fit an addition-elimination mechanism for the PhSion, and an elimination-addition route for reaction of the MeO- ion. However, deuterium exchange is not sufficient indication for the latter route, since (11) exchanges its hydrogen faster that it can undergo the vinylic substitution by MeO- ion (Ghersetti et al., 1961). Values of ArSOz. CD=CH. SPh

PhS-/MeOH

ArSOz. CD=CHCl

MeO-/MeOH

ArSOz. CH=CHOMe (11-a-D)

ArSOz. C H = C M e . SPh

ArSO2. CM-CH.

SPh

PhS-/MeOD

t -ArSOz

PhS-/MeOD

.CH=CMeCl

MeO-/MeOD

ArSOz. CD=CMeOMe (12) MeO-/MeOD

ArSOz. C M e C H C 1 t ArSOz CMe==CHOMe (13)

.

86

ZVI RAPPOPORT

kexch/k8ubs are 50, 75 and 120 for cis- and trans-chloro-(11), and for trans-bromo-(1l),respectively. Moreover, no deuterium isotope effect was observed for the reaction of PhS- and MeO- with (11-a-D). The results are consistent with a preliminary base-catalysed fast reversible equilibration of the a-hydrogen leading to exchange. Concurrent attack of the base at the /3-carbon competes with trans elimination to acetylene, and exchange could be observed for either mechanism, or even in the absence of substitution (Scheme 7). With a weaker base, e.g. PhS-, the exchange is slower than substitution. The trans isomer favours addition-elimination, while the cis isomer reacts, at least partially, via the acetylenic intermediate, showing an element effect. The absence of an isotope effect suggests an ElcB mechanism. ArSOz .i%I-CH(OR)Hal

(2). kr t- ArSOz. CH=CHHel+

RO-

.-

(I),

ki

(-1).

-

ArSO2 .C=CHHd k-1

ArSOz . C=CH

ArSOZCH=CHOR

1

(5).

+ROH

ArSO2. CH=CHOR SCHEME 7

Addition-elimination follow the ( - 1) e (1) + (2) -+ (3) route, with exchange when k l , k-l $ k2, and without exchange when k 24k l , while elimination-addition follow the ( - 1) GZ (1) + (4) 3 ( 5 )route. Since both the stereochemical results and the exchange experiments are inconclusiveregarding competition of the two reaction routes for the cis isomer, the dissection of the reaction into the contributions of the two routes requires the isolation or the estimation of the intermediate. Under suitable conditions, p-toluenesulphonylacetyleneis the main product from bromo-(ll), while it is only detected by infrared spectroscopy during the reaction of chloro-(11). Dissection of the overall substitution rate constant (k,) into contributions from elimination-addition (keum) and addition-elimination (kBUb)is possible when the rate of the alkoxidecatalysed addition of alcohol to the intermediate acetylene (kadd) and the concentrations of the latter during the reaction are known. Such analysis for cis-(11)and (12) (Table 10) shows that at 0" the contributions of the two processes to the overall rate are nearly equal, but the importance of the elimination-addition route increases with the temperature, kexm/ksub= 3.0 and 1.4 for (11)and (12)respectively at 25" (DiNunno

TABLE10 Rate Constants and Activation Parameters for the Various Processes in the Reaction of cis-ArSOzCH=CRCl with MeO- in Methanol at 0 ' "

H Me

a

0.96 0-38

4.40 1.28

21.2 22.2

+8 +10

0.51 0.17

24 24

+26*5 +13

0.45 0.21

17 20

-1 -1

1.1 0.8

The Erst fourvaluesareobserved,theothersarecalcdated. (kinM-lSe~-~, E,in kcalmole-1, AS* ine.u.) Apparent values for the overall process.

88

ZVI RAPPOPORT

et al., 1966). Dissection of the activation parameters shows that the high overall activation energy for (11)is composed of the activation energy of the addition-elimination route, which is identical with that of the trans isomer (reacting via this route alone), and a higher value as expected for the elimination-addition route. The similarity in rates for the two processes results from activation entropy compensation. The high element effects for the reactions of amines with (11)and (12) suggest multiplicity of mechanistic routes. The second-order kinetics and the very slow exchange of cis-bromo-(11-a-D) in isopropanol fit addition-elimination (Ghersetti et al., 1965). I n methanol, kexoh/kBUb values for reaction of cyclohexylamine with cis and trans-chloro-(11) and cis- and trans-bromo-(11) are 13, 11, 20 and 23, respectively, and 0.9, 0.6, 1.4 and 0.8 for the corresponding reactions of di-n-butylamine. While trans-bromo-(11) and cis-chloro-(11) showed normal kinetics in methanol and in ethanol, the rate constants with cis-bromo-(11)and (12) decreased with time, but steady second-order behaviour could be achieved by addition of the perchlorate of the amine used. While this fits an amine-promoted elimination-addition, where the ammonium salt formed shifts the equilibrium to the left (equation 15), the slow -

ArSOzCH=CHHal+ RNHz

+ ArSOzC=CHHal+

RNHj

(15)

exchange in the less acidic isopropanol suggests that the amines themselves react via addition-elimination, while the more basic alkoxides, formed according to equation (16) are responsible for the eliminationaddition route. RNHz + R’OH

+ R’O-+ RNH:

(16)

The values of k,/k, (1.6-2.2) and of k,,/kcl (108) for the cis-p-halo-pnitrostyrenes-Me0- reaction (Marchese et al., 1966, 1968) point to an elimination-addition, while the trans isomers show negligible hydrogen exchange and react by a route analogous to (1) + (2) --f (3) of Scheme 7. Both the kci8/kt,,,, ratios and the activation energies may be misleading, as is clear from Table 11. The Table summarizes the various kinetic parameters for several pairs of cis-trans isomers which are assumed to react via the elimination-addition and the addition-elimination routes, respectively. The k~,/kt,,, ratio is over 400 for the bromo compound, but only 3.3 for the chloro compound. On the other hand, the activation energies for both bromo compounds are similar, while that for the cischloro isomer is 5 kcal molev1 higher than that for the trans isomer. Positive activation entropies seems to be associated with the elimination processes, and negative ones with those which are assumed to be addition-eliminations. The cis-chloro compound gives only 10%

TABLE11 Kinetic Parameters for Comparison of the Elimination-Addition and the Addition-Elimination Routes with MeO- ion in Methanol cis isomer

Substrate

E.

AS'

2,4-(NO&C&. CH=CHBr 4-NOzC6H4.CH=CHCl 4-NOzCsHd.C H d H B r p-MeCeH4SOzCH4HCI p-MeCeHdSOzCH=CHBr pMeCsH4SOzCH==CMeCl MeCCl=CH .CNb M e C B d H .CNb

20 29 25 24"

+6 +12 +9 +26"

24" 22 18

+13' +12 -1

kBr kc,

108 185 352 6.5

tram isomer

5 k,

Em

AS'

1.6 2.2

19 24 25 17

-7 -7 -3 -8

1-08 1.36

24 20

+22 +15

k,,

k,,

0.88 0.84 257

kl3

k,

0.99

1.03 1.06

kd, ktranr

149 3.3 444 0.7 332 0-47 0.012

Reference

Marchese et al., 196th Marchese et al., 196813 Marchese et al.,1968a D~NUMO et al., 1966 Maioli et al., 1960 DiNunno et al., 1966 Theron, 1967 Theron, 1967

H

I4

9

Data for the elimination-addition process. Reaction with EtO- ion; cis and tmm refer to relationship between the Me and the CN groups.

?I

0

2

90

Z V I RAPPOPORT

substitution via addition-elimination. Contrary to the behaviour of other systems (Miller and Lee, 1959)the absence of hydrogen exchange with the solvent and the low isotope effect points to a concerted elimination with high carbanionic character at C,. Isolation of acetylene from cis-/3-chIoro-cc-p-methoxybenzoylethylene, and the activation energies of 19.1 and 13.6 kcal mole-1 for the cis and the trans isomer, respectively, indicates the operation of eliminationaddition (Montanari, 1967). 2-Butynonitrile is the main product from excess /3-halocrotononitriles with EtO- and PhO- ions. Excess nucleophile adds to the acetylene forming initially trans (methyl and cyano groups) nitriles, which subsequently isomerize to the cis isomers. The kB,/kclratios of 6.5 and 257 for MeCX=CH

- HX .C N +RO- + MeC=C.

CN

+ROH

.

MeC(OR)=CH CN

the cis and the trans series, respectively, the values of kci8/ktTans (0.47 and 0.012 for the chloro and the bromo series) and the small element effect with EtO- ion (except for the bromo compound) fit an ElcB mechanism. The addition of a /3-methyl group to ,!?-chloroacrylonitrile, which reacts via addition-elimination, is therefore sufficient to change the reaction course, probably by decreasing the electrophilicity of the /3-carbon. Whereas the stereochemistry and the ktrans/kcisvalues for most thio nucleophiles reactions point to addition-elimination, the ratios kt,,/kcia = 10-2, and kBr/kC1= 33, the deuterium exchange and the isolation of intermediate acetylene in the 8-bromocrotononitrile-EtSreaction suggest that this is a rare case of an elimination-addition with a thioanion (Theron, 1967). 2-Butynonitrile (180) and mixtures of both substitution isomers are formed in the reaction of Grignard reagents with /3-halocrotononitriles (Boularand and Vessibre, 1967). Under similar conditions, the isomer ratios are identical starting either from the cis or the trans substrate. Moreover, tram-p-bromocrotononitrile gave 1 :1 and 1: 1.8 cisltrans ratios of MeCR=CH. CN for R =Et and Ph, respectively, exactly the same ratios as are found for the reactions of (180) with EtMgBr and PhMgBr.

, + Me,/c=c /CN

Me Br

‘CN

Et

CN

Et

‘H

EtMgBr

MeC=C.CN

The corresponding halocrotonate esters react with EtO- mostly via the P,y-elimination-additionroute. However, the isolation of a 2-butyne

91

NUCLEOPHILIC VINYLIC SUBSTITUTION

ester rather than a 2,3-butadiene ester from ethyl trans-j3-bromocrotonate at low base/substrate ratio indicates a,/?-elimination. The ratios kH/kD= 1.8 and kBr/kCl= 17, as well as the incorporation of deuterium from the solvent, confirm this interpretation. Reisolated starting material shows no such incorporation, which suggests that the step analogous to (2)of Scheme 7 is much faster than step (1) (Theron, 1967).

B. The /?,/?-Elimination-AdditionRoute (The Carbenic Mechanism) This is a relatively rare route in which both elements of HX are eliminated from the /?-carbon, leaving a carbene (181)(equation 17). Among other reactions, the carbene may also capture the nucleophile, giving a /?-substitutionproduct. CHX=CHY

+ baee, -HX

:C=CHY

+NuH

___j

CHNu=CHY

(17)

(181)

Both l-bromo-3-methyl-1,2-butadiene (182)and 3-bromo-3-methyl-lbutyne (183)give in aqueous ethanol the same product mixture, containing mainly propargyl alcohol and ether, but no allenic derivative (Shiner and Humphrey, 1967). I n the presence of both PhS- and OHions, an identical product mixture (32% allenic and 52% propargylic thioether) is again formed from both isomers. This and the rate acceleration by base were ascribed to the formation of a common allene-carbene intermediate which was written as (184at)184b)(Scheme 8). Since the exchange rate of the terminal allenic hydrogen is 10-20 times faster than the rate of formation of other products from (183),the proton is MezC=C=CHBr

Me2CBr-CdH

92

ZVI RAPPOPORT

probably lost in a pre-equilibrium rather than in a concerted /3,/3elimination. The rate depression by KBr points to a loss of bromide ion in the rate-determining step. Either EtO- or PhS- ion could be captured by the carbene. Without base, PhS- ion gave different product distributions from the two isomers, e.g. a 55 :45 ratio of (185) to (186) from (183), with no hydrogen exchange. This was explained by nearly equal contributions of SN2and SN2' mechanisms. The formation of t-butoxyvinyl ether (188) from bromomethylenecycloheptene (187) and t-BuO- proceeds via intermediate alkylidenecarbene (Erickson and Wolinsky, 19.65).

C . The /3,y-Elimination-Addition Route (The Allenic Mechanism)

A proton on a y-carbon may be eliminated in competition with a proton on the a-carbon, and subsequent addition of the nucleophileto the central carbon atom of the intermediate substituted allene (189) would result in an overall substitution (equation 18). In this p,y-eliminationR'RZCH-CX=CR3R4

+B

-HX- R1R2C=C=CR3R"

+ NuH ---+ R ~ R ~ C H - C N U = C R ~ R ~ (1 8)

addition route, a strongly basic nucleophile and an activated y-hydrogen are required, an element effect and deuterium incorporation would be observed, and isolation and independent study of the intermediate are desirable. Stereochemicallimitations are small, since the trans configuration of the y-hydrogen and the /3-leavinggroup is achieved for either the cis or the trans starting material, which differ only in the configuration at the a-carbon. Beltrame et al. (1964) suggested this route for the reaction of 1,l-diphenyl-2-halopropene (190) with EtO- ion which gives the substitution product (191) and a cyclobutane (192) which is a dimer of the alleged intermediate allene (193). The reaction is characterized by an element effect (kB,/ko= 2a-2.79 at 80-126"), and by rate coefficients which are

NUCLEOPHILIC VINYLIC SUBSTITUTION

93

200-fold higher than those of the l,l-diphenyl-2-haloethyleneswhich react by addition-elimination. The vinylic ether (191) is the main product although more (192) is formed when X = Br than when X = C1. The ratio (191)/(192) is dependent on the ratio (Et0-)/(190), being e.g. 3.6 and 10 for ratios of 2.5 and 10 of EtO- to (190, X=C1) at 125-130'. The most probable route to (192) is by dimerization of (193), but (191) could be independently formed in an addition-elimination. This is excluded, since in this case a rate determining base-promoted dehydrohalogenation for formation of (193) requires the ratio (191)/(192) to be independent of the (Et0-)/(190) ratio, and (190) would also be expected to be less reactive than Ph,C=CHX, contrary to what is found. Alternatively, if both (191) and (192) are formed from (193), their ratio should depend on the base concentration if the rate constants for eliminaand nucleophilic addition (kadd) are of comparable magnitude. tion (Slim) It was found (Beltrame et aE., 1967a) that indeed only (191) and (192) are formed from the independent reaction of (193) with EtO-, and that the above rate constants and that for the dimerization (,%dim)were similar in magnitude. At 125O, kelim(C1) = 3-2x kelim(Br) = 5-7 x kadd = 3.2 x M - ~sec-l. The good agreement of the and kdim= 7.5 x calculated (191)/(192) ratios based on these values with the observed ones argues in favour of (193) as an essential substitution intermediate which does not accumulate owing to its rapid transformation to (191) and (192). The low element effect fits an E2 mechanism tending towards ElcB elimination. I n principle, the nucleophile can attack the allene at two different positions, but the products show exclusive attack at the central carbon atom, similarly to other nucleophilic additions to allenes (Eglinton et al., 1954; Stirling, 1964b; Taylor, 1967). This may result from the stabilization of the carbanion (194), formed by attack at this position, by the two phenyl groups. The ion (194) may be protonated at either one of the terminal positions of the allenic system, and low amounts of

(195) may be formed in addition to (191) in the reaction of (190) with ethoxide ion. It was assumed that the prototropic rearrangement (195) -+ (191) would, however, be fast, since in the similar addition of methanol to phenylsulphonylallene (196) (Stirling, 1964b)the kineticallycontrolled product (197) isomerizes to its conjugate isomer (198). The

94

ZVI RAPPOPORT

compound (196) is itself formed from 2-chloro-3-phenylsulphonylpropene, and formation of (197) is again due to the &y-eliminationaddition route (Stirling, 1964~). Ph&H-CH(OEt)=CHz (195)

PhSOZCH==C=CHz +MeOH + PhSO&H-C(OMe)=CHz (196)

+ PhSO&=C(OMe)Me

(197)

(198)

Formation of (195) is another type of “substitution with rearrangement ” reaction (route VIII of Scheme l), in which migration of the double bond takes place. Competition between the p,y- and the a$-elimination-addition modes is possible in the systems studied by Bottini and coworkers. N-(2Bromoally1)alkylamine (199) with NaNHz in liquid NH:, gives mainly 1-alkyl-2-methyleneaziridine(200) together with a lower amount of N-alkylpropargylamine (201) (Pollard and Parcell, 1951; Bottini and Roberts, 1957). The driving force for this intramolecular substitution of the unactivated vinyl bromide (199) is probably the presence of the CH2=CBr-CHzNHR

NaNHs

CH2=C-CH2

\N/

+

HC=CCH2NHR

I

R (199)

(200)

(201)

very strong nucleophilic amide ion in the vicinity of the reaction site. The four different routes which were considered a priori (Bottini and Roberts, 1957) were : (1) Direct intramolecular substitution (equation 19). (2) An addition-elimination sequence via (203) (equation 20). (3) A P,y-elimination-addition via the aminoallene (204) and the carbanion (205) (equation 2 l ) , and (4) the a$-elimination-addition via (201) (equation 22), (Scheme 9). Isolation of high yields of (201) from the analogous reaction of N(2-chloroallyl)alkylamineargues against its involvement as a substitution intermediate. The sensitivity of the acetylene to nucleophilic addition rather than its mere isolation should be considered as part of the evidence concerning its role as an essential intermediate. Since neither (199) nor (200) exchange their CH2-hydrogens with the solvent, the isolation of labelled (200) from the reaction in tritiated liquid ammonia excluded (1) as the main substitution, while (2) and (4) are excluded since the exocyclic methylene was not labelled. The incorporation of tritium at

I/‘B-FG

t t

NUCLEOPRILIC VINYLIC SUBSTITUTION

6-y

95

96

Z V I RAPPOPORT

the methylene ring protons of (200) could be accounted only by the allenic mechanism (3), via (204) + (205) (Bottini and Olsen, 1962). It was suggested that in the transition state for the formation of (205), i.e. in (206), the electron pair of the nitrogen attacks the nearest p-orbital whose axis lies in the plane defined by the three allene carbon atoms and the nitrogen, pushing back the incipient exocyclic carbon atom from the line of the other two carbons.

Hence, in the competition between @3- and p,y-eliminations,the latter is preferred. The (200)/(201)ratio is only slightly sensitive to the nitrogen substituent R. For several, not too large R groups, the ratio is 3-4: 1 (Bottini and Dev, 1962; Bottini et al., 1963). The importance of steric effects is shown by the low (32:68) ratio for R=t-Bu. When 6 , ~ elimination is not possible, q3-elimination takes place in preference to direct substitution. The acetylene (208) and not the azetine (209) is formed from (207) (Bottini et al., 1962).

Nucleophilic attack at the terminal atom of an allenic system can give another type of rearranged substitution product, where the nucleophile is attached to the allylic position (equation 23) (route I X of Scheme RlR*CH--CX=CR3R"

+ Nu-

+ R'RZC=C=CR3R" - HX

+Nu-

+ +H+ R1R2CNu-CH=CR3R4

(23)

1). Intramolecular substitution by the alkoxide of N-n-butyl-N-

(2-haloallyl)ethanolamine (210) gives exclusively 3-t-butyl-2-vinyloxazolidine (211) and no substituted morpholine (212) (Bottini et al., 1964),possibly owing to the higher stability of the five-membered ring. The reaction between ethyl p-chlorocrotonates and EtO- was reported to give only one ethoxy ester (Jones et al., 1960). Reinvestigation has

-

NUCLEOPHILIC VINYLIC SUBSTITUTION

HzC=CCl-CHz-N(t-Bu)-CH2.

97

NHa-

CHzOH

shown that, all four cis and trans chloro and bromo esters (213) formed also ethyl 2,3-butadienoate (Theron, 1967). trans-(213) also gave the acetylene (216), and the substitution product was shown to be cis (methyl and carbethoxy) (218). The kBr/kC1ratios of 1.45 and 17 for cis- and trans-(213), the keis/ktrans values of 0.21 and 2.5 for X=C1 and X = B r , respectively, and the ICH/kDvalues of 1.0 and 1.8 for cis- and trans-(213) fit B,y-elimination-addition. Deuterium from the solvent was incorporated at both the methyl and the vinyl positions of (218), but not in recovered (213). Of the three routes for formation of (218) from (215) (Scheme lo), (215) --f (218) is excluded, since vinylic deuterium was not incorporated. Both the (215) --f (217) --f (218) and the (215) -+ (216) + (218) routes account for the isotope exchange. The independent addition of ethanol to (215) gave both (218) and an isomer, which was assumed to be (217) formed by kinetic control. The most probable substitution course is therefore (213) + (214) --f (215) --f (217) --f (218). C H I . CX=CHCOaEt (213)

EtO-

-

CHz .CX=CHCOzEt (214)

CHZ=C=CHCOzEt

EtOH

I

CHs.C(OEt)=CH.COzEt

/

(218)

SCHEME 10

Competition with cr,,!l-eliminationwould be less important if a strong The

- M substituent is attached to the y-, rather than t o the a-carbon.

Z V I RAPPOPORT

98

bromophosphonate (219) gives the substituted enamine (222, X = NMe,) by direct addition to the intermediate allene phosphonate (220), where the formation of the rearranged product is governed by the conjugation achieved in the product. A variant of this route with EtO- ion is the allene (220) -+ acetylene (221) rearrangement which is followed by addition to give again (222, X = OEt) (Sturtz, 1967).

II

0 (219)

V. THES,1 ROUTE Formation of vinylic carbonium ions by various routes has been suggested in recent years by several workers. Addition of electrophiles, mostly protons, to various acetylenes is the most investigated pathway (Whitlock and Sandvick, 1966; Richey and Buckley, 1964; Noyce et al., 1965; Letsinger et al., 1965; Bott et al., 1964, 1965; Peterson and Duddey, 1966; Peterson and Kamat, 1966; Fahey and Lee, 1966), but their formation was also suggested in the reaction of vinyltriazenes in acidic solution (Jones and MilIer, 1966) or in the deamination of vinylamines (Curtin et al., 1965). However, solvolytic formation of vinyl cations has been investigated in very few cases. p-Amino, p-acetamido- and p-methoxy-a-bromostyrenes (219) give, in 80% aqueous ethanol, only the corresponding acetophenones. aBromostyrene forms mainly acetophenone and some phenylacetylene, and the p-nitro derivative gives only p-nitrophenylacetylene (Grob and Cseh, 1964). There are several arguments favouring the suggested SN1 route for all the compounds excluding thellast one. The reactions are f i s t order during a run in the presence of triethylamine, and independent of its concentration, whereas elimination-addition and additionelimination are dependent on the base concentration. a-Bromostyrene solvolyses 10 times faster in 50% ethanol than in 80% ethanol, as expected for a reaction with a highly polar transition state. Finally, the substituent effect is very large: the solvolysis rate changes by nine

99

NUCLEOPHILIC VINYLIC SUBSTITUTION

orders of magnitude between the p-amino and the unsubstituted compounds (Table 12). Although Hammett's p+ was not calculated, its value should be negative and high, contrary to those of the additionelimination route (Table 8). The reactivity differences are mainly due to activation energy changes. TABLE12 Rate Constants for the Solvolysis of a-Bromostyrenes"

R in p-RCeHr. CBr=CHz

Me0 NHCOMe H

104icl at 100'

E,, kcal mole-'

AS;,,, e.u.

2.3b 3.6 x 10-5 9.3 x 10-6' 4.2 x 10-gb

20.6 27.8 28.7 34.1

- 4.3 - 6.7 - 12.3 - 7.8

In 80% ethanol in the presence of Et3N. Extrapolated value.

Both the ketone (226) and the acetylene (227) could be visualized as arising from a rate-determining formation of the carbonium ion (224) followed either by elimination of a proton, or by addition of water molecule and ketonization of the formed enol (225). Since the bond

cleavage is rate-determining, electron-donating substituents will stabilize the carbonium ion by contributions of structures such as (228). Since this requires coplanarity of the double bond and the benzene ring, (224) has a linear allenic geometry at C,.

Solvolysis of trianisylvinyl bromide (229, X-Br) is only 1.7 times faster than that of a-bromo-p-methoxystyrene (Rappoport and Gal, 1968). The participation of the neighbouring /3-anisyl groups in the solvolysis, if any, is small, probably because the groups are held too far

100

ZVI R A P P O P O R T

by the rigid geometry of the double bond. The element effect for (229), (kB,/kcl= 58 at 120') points to considerable bond cleavage in the rate( p-MeOCeH4)zC=C(CeH40Me-p)Hal

(229)

determining step. The m values of the Grunwald-Winstein equation, as calculated from the rates at two different aqueous alcohol compositions, are 0.63 for (223,Ar=Ph) at 170" and 0.53 for (229,Hal=Cl) a t 120'. These are somewhat lower than those for S,1 reactions in saturated systems (Winstein et al., 1957), probably owing to the higher reaction temperatures. I n the solvolytic decarboxylation of potassium trans p-halocinnamates (230)and acrylates in aqueous ethanol, both the ketones (226) and the acetylenes (227)(e.g. 12% acetophenone from (230,Ar=Ph) were found. The cis isomers (231)gave only acetylenes by an assumed concerted fragmentation (Grob, et al., 1964). The intermediate formation Ar

\ ,c=c

/H

-COa, -Br-

ArCOCHs -k ArCECH

_____f

Br

Ar\ Br'

,coz-

,c=c ,

'H

-Cot, -Br-

ArCZCH

of vinylic carbonium ion was suggested by the strong effect of electrondonating substituents. The 400-fold rate increase of 13-bromocinnamate solvolysis over that of u-bromostyrene, which forms the same final product, was ascribed to the stabilization of the intermediate by an internal solvation of the opposite charges as in (232). Capture of (232) by the solvent, ketonization and decarboxylation of the /I-ketoacid formed gives (226).

o=c /? ;\

;

H-C=C-R

Jacobs and Fenton (1965) suggested that the allenic carbonium ion

(234a)is an intermediate in the formation of the propargyl alcohol (235)

N U C L E 0 P H I L I C V I N Y L I C 9 U B S T I T U T I 0N

101

by the hydrolysis of the haloallene (233).The alcohol (235)is formed by an easier nucleophilic attack on the positive carbon of (234b)rather than PhzC=C=CPhX (233)

- X__f

+

PhzC=C=CPh (234a)

t--)

+

Ha0

PhZC-CGCPh

+PhzC(OH)-CGCPh

(234b)

(235)

X = C l , Br

on that of (234a).However, the allenic ether (237)was obtained from the bromide (236)with MeO- ion. The preferential attack at the allenic Me&. CPh=C=CBrPh

MeO-/MeOH ____f

Me&. CPh=C=C(OMe)Ph

(236)

(237)

position of the carbonium ion reflects steric hindrance by the bulky t-butyl group to attack at the propargylic position. While the structural similarity of (236)and a-bromostyrene may indicate a similar mechanism, the suggested S,1 route is still tentative. Zugravescu et al. (1958) considered the reaction of /3-aroyl-j3bromoacrylic acid salts (238)with base to be an S,1 process via (239)on p-RC&.

CO .CBr=CH. COT+ NaOH

.

+

p-RCaH4. CO C=CH. CO;

(238)

4

products

(239)

the evidence of first-order kinetics at 65' for R =Me, Me0 and H. However, the reaction order is between one and two for R = Me0 and Me at 55", and for R = H at 45", and electron-donating substituents decrease the rates relative to R = H, p being 0-81. The intermediate order was ascribed to an S,2 contribution and the substituent effect was explained as follows : For R = H, the conjugation of the .Ir-electrons of the double bond with those of the carbonyl group decreases their conjugation with the p-electrons of the halogen, thereby increasing its mobility. With the electron-richer phenyl residue, conjugation with the ring increases at the expense of conjugation with the carbonyl group, and the p - 7 ~conjugation increases, resulting in decreasing halogen mobility. However, the substituent effect is opposite to that for the SN1 route as discussed above, but fits an addition-elimination path. The kinetics at 65" may be explained by a fast base-catalysed addition forming the a,P-adduct (240),followed by its rate-determining solvolysis. Decreasing the temperature or substitution by electron-donating substituents p-RC&.

CO .C(0Me)Br-CHz

(240)

.CO;

102

ZVI R A P P O P O R T

decrease the rate of formation of (240), so that competition between the two steps becomes important, and an intermediate reaction order is obtained .

VI. SUBSTITUTIONS FOLLOWING PRIMARY REARRANGEMENTS (THEPROTOTROPIC ROUTES) I n systems such as (241) which are capable of prototropic change, basic nucleophiles could cause preliminary rearrangement to (242). The migration of the double bond places the leaving group in the reactive allylic position, and its replacement becomes very facile. The primary substitution product (243) is the allylic one, but further prototropy could form the vinylic substitution product (244) formally derived directly from (241) (equation 24). This route, which requires highly R'CHzCH==CR2X (241)

RO-

R'CH=CH

RO.CHRZX +

(242)

RlCH=CH. CHR20R (243)

RO-

RlCHz. CH=CRZOR

(24)

(24)

basic nucleophiles for the two prototropic rearrangements, would give the same substitution product starting from either one of the two geometric isomers, owing to the formation of the common product (243). A priori both (243) and (244) could be observed (routes XI11 and XIV of Scheme 1). cr-Bromocrotonic acid (245) (Owen, 1945) and a-bromoisocrotonic acid (246) (Owen, 1945; Pfister et al., 1945) were found to give the same a-methoxycrotonic acid (249) with methanolic hydroxide ion. Some u,p-dimethoxybutyric acid (250) and p-methoxycrotonic acid (252) were also formed (Scheme 11). Other alkoxides react similarly but the amount of the normal substitution product decreases at the expense of the p-alkoxycrotonic acid with increasing bulk of the alkoxide, in the order MeO- > EtO- > i-Pro- > t-BuO-, and with t-BuO- only the latter product was formed. While (250) and (252) probably arise from (249) and (251), (249) itself could be formed either via abnormal addition to the elimination product tetrolic acid (253), via the rearrangementsubstitution pathway (247) + (248), or via direct substitution through a long-lived carbanion. A differentiation between those routes has not been made for a-bromocrotonic acid. However, a-bromoacrylic acid, which is incapable of a prototropic change but should be more reactive in direct substitution,

103

NUCLEOPHILIC VINYLIC SUBSTITUTION

MeCH(OMe).CH(OMe).COzH

MeCH==C(OMe). c O 2 H MeCEC. COzH (253)

H

Me H

t

(249’

CHz=CH.CHBr .C02H \

/

,C=c

\

COzH

__t

(247)

Br

MeCH(OMe)CHBr.COzH

(2461

CHz=CH .CH(OMe).COaH (248)

+MeC(OMe)=CH.

(2511

COaH

(252)

SCHEME 11

gives no normal substitution product (256). Only the methanol addition product (254) and the abnormal substitution product (255) are formed (Owen and Somade, 1947). H&=CBr.COzH

RO__f

CH2(0R).CHBr.COzH (254)

RO-

CH(OR)=CH.COaH (255)

The structurally related a-bromocinnamic acid (257) gave only dehydrobromination with alkali (Owen and Sultanbawa, 1949a). PhCH=CBr .COzH (257)

Direct evidence for the prototropic route in a substituted crotonic acid was obtained from reactions of p,p-dimethylacrylic acid (258) (Owen and Sultanbawa, 1949a). With alkoxides, both unsaturated alkoxy acids (259) and (260) were isolated, and differentiation between the substitution-rearrangement route (258) + (259) + (260) and the rearrangement + substitution + rearrangement route (258) + (261) + (260) + (259) could be made. According to the former, the amount of (260) should increase at the expense of (259) with the progress of the reaction, while according to the latter the opposite is expected. It was found that (260) decreased, while (259) increased, during the reaction, and this evidence in favour of the prototropic rearrangement, coupled with the inertness of bromoacrylic acid, suggests that the same mechanism operates also for a-bromocrotonic acid. The absence of (248)

104

ZVI RAPPOPORT

in the latter reaction was ascribed to a faster and more complete (248) + (249) rearrangement, At equilibrium there is 90% of the u,p-compared

RO-

MezC=CBr. COzH (258)

CHZ=CMe.CHBr.COzH

RO__f

MezC=C(OR) .COzH (259)

CHz=CMe. CH(OR).COzH

(261)

(260)

to 10% of the p,y-unsaturated u-methoxy acid. For the methoxycrotonic acids, the u,p-isomeris practically the only one in the equilibrium mixture. Mixtures of u-methoxy-u,P- and &y-unsaturated acids have been obtained from other reactions, such as that of 2-bromo-2-pentenoicacid with sodium methoxide (Alles and Sultanbawa, 1956), and the relative amounts of the two acids depend on the position of the prototropic equilibria in the systems. Both isomers were obtained from u-bromocyclohexylideneacetic acid (262) by alkoxide substitution, but the

.

CBr COzH (262)

u,P-derivative was only 5% of the substitution product (Newman and Owen, 1952). I n the same conditions, both the “abnormal substitution product ” (264) and y,y-dimethoxycrotonic acid (265) are formed from

.

.

MeOCHz CH=C(Br) COzH + (263)

.

.

MeOCHz CH(OMe)=CH COzH + (Me0)zCH. CH=CH (264)

.COzH

(265)

a-bromo-y-methoxycrotonic acid (Owen and Sultanbawa, 1949b). The product (261) is formed by another variant of the route, as the initial prototropy is probably followed by substitution with allylic rearrangement. The effect of the y-methoxy group on the reactivity of the allylic halogen may be sufficient to bring about SN1solvolysis, in which MeOion is captured at the positive end of the allylic system. When the leaving group is attached to the central carbon atom of a prototropic system, it remains vinylic after the prototropic change. Whereas the substitution in the rearranged compound is not necessarily easier, the product structure may be determined by this rearrangement.

105

NUCLEOPHILIC VINYLIC SUBSTITUTION

Reactions of /?-halovinylaceticacid derivatives (266)with nucleophiles give crotonic acid derivatives (274) (VessiBre, 1949; Theron, 1967) by prototropy either preceding the substitution step, or following it. For example, /I-halovinylacetonitriles (X= CN) gave only /?- substituted cis-crotononitriles with excess EtO- or PhO- ions. Allenic and acetylenic nitriles were isolated in the reaction course. The occurrence of primary rearrangement when Hal=Cl was evident by the isolation of /?-chlorocrotononitriles from the reaction of (266, X = CN, Hal = C1) with these anions, while the bromo-compound did not give any rearrangement. With thio nucleophiles, the main products were the unrearranged derivatives, formed by addition-elimination process. The corresponding esters (X = C0,Et) gave only rearranged substitution derivatives with oxyanions, and mostly unrearranged ethyl 2-phenylthio-3-butenoate (269) with PhS- ion. The cis crotonic esters formed were probably derived from a post-isomerization reaction. These results, coupled with the study of exchange (e.g. the substitution

r

CHZ=C(Hal)CHzX

-41

CHZ=C(Hal)-CHX (267) --Hal-

+ Nu-

CH2 .C(Hal)=CHX (270)

+H+

I CH3 .C(Hal)=CHX

(271)

l

1

SCHEME 12

TABLE13 Substitution Routes for CHz=C(Hal).CHzX by Various Nucleophdes

X

Hal

Nucleophile

Substitution product

Substitutionroute N

C1, Br C1, Br Br C1, Br Br

c1

PhSEtSEtOEtOEtS-, PhSEtO-

CN

c1

PhO-

CN

Br

PhO-

CN

c1

EtS-, PhS-

COzEt COzEt COzEt

CN

CN COzEt

(266) -+ (269) --f (274) (266) -+ (267) 3 (268) --f (269) 3 (274) (266) -+ (267) -+ (268) -+ (269) -+ (274) (266) -+ (267) 3 (268) -+ (269) + (274) (266) -+ (267) -+ (268) -+ (269) -+ (274) (266) + (267) 4 (270) -+ (271) 3 (272) -+ (273) -+ (274)+ (266) -+ (267) + (268) 3 (273) -+ (274) (266) -+ (267) --f (270) + (271) + (272) -+ (273) -+ (274)+ (266) -+ (267) -+ (268) -+ (273) -+ (274) (266) -+ (267) 3 (268) -+ (269) -+ (274)+ (266) 4 (267) -+ (268) -+ (273) --f (274) (266) + (267) --f (268) 3 (269) --3. (274)+ (266) -+ (267) + (270) 3 (271) -+ (274)

2 w

P id id

*

+d 0

w

H

NUCLEOPHILIC VINYLIC SUBSTITUTION

107

of the esters by EtS- ion was accompanied by an a-hydrogen exchange with the solvent), has shown the existence of many variants of the rearrangement-substitution routes, depending on the substrate and on the nucleophile. These are summarized in Scheme 12 and in Table 13 (Theron, 1967). VII. SUBSTITUTION VIA Two SN2‘ REACTIONS When halogen atoms are attached to a vinylic carbon and also to one allylic to it, an SN2’ process converts the vinylic halogen into an allylic one, while the formerly allylic one is replaced, and a new olefin is formed. Another SN2‘ attack at the new terminal vinylic carbon would result in the replacement of the original vinylic halogen. The vinylic halide can thus be exchanged in two consecutive SN2’ reactions. This mechanism was suggested for the reaction of 1,3-dichlorotetrafluoropropene with F- which gives 1,1,1,2,3,3,3-heptafluoropropane, by nucleophilic addition of F- to the substitution product (equations 26-27) (Miller et al., 1960). SN2’ .CClFz +F- * CClFz .CF=CF2 + C18N2’ CClFa .CF=CFz +F- +CFz=CF. CF3 + C1H+ C F z S F . CF3 + F- +CF3. EF .CF3 * CF3. C H F .CF3

CClF=CF

(26) (26) (27)

The reversible fluoride ion-catalysed rearrangements of perfluoroolefins (Miller et al., 1960) may also cause vinylic fluorine-fluorine exchange by a similar mechanism.

VIII. SUBSTITUTION IN THE PRESENCE OF METALSALTS Vinylic substitutions in otherwise unreactive systems can take place easily in the presence of metal salts. The chlorine atom of vinyl chloride is replaced by acetic acid, isopropyl alcohol and n-butylamine in the presence of catalytic amounts of PdC1, in iso-octane (Stern et al., 1966). CHz=CHOAc CHZ=CHCl

CHz=CHOCHMe2 CHz=CHNHBu

The mechanism was not specified but it was suggested that the reaction involved formation of a vinyl chloride-PdC12 complex, which is followed

108

ZVI RAPPOPORT

by displacement of chlorine by the nucleophile from the solution or by exchange with a nucleophilic ligand. If the complex is structurally similar to the ethylene-PdCl, complex, back donation of electrons from the metal to the double bond would.increase the electron density at the substituted carbon and facilitate the carbon-halogen bond cleavage. The exchange of the acetate groups of vinyl acetate with those of CD,. C02H, which is catalysed by mercuric acetate, was claimed to involve direct displacement of the vinylic acetate (Samchenko and Rekasheva, 1965), although an electrophilic addition-elimination seems more plausible.

ACKNOWLEDGMENTS The author is indebted to Drs. P. Beltrame, E. W. Cook, J. Klein, S. I. Miller, G. Modena, F. Montanari, J. D. Park, F. Theron, W. E. Truce and R. Vessibre for kindly making available unpublished data and for commenting on specific points. Thanks are especially due to Professor S. Patai who critically read the whole review, suggested the terms geminate” and “vicinal” for the element effects, and made many valuable suggestions. 66

REFERENCES Aguiar, A. M., and Archibald, T. G. (1967). J . Org. Chem. 32,2627. Aguiar, A. M., and Daigle, D. (1964). J . Am. Chem.SOC. 86, 2299. Aguim, A. M., andDaigle, D. (1965a). J. Org. Chem. 30,2826. Aguiar, A. M., and Daigle, D. (1965b). J. Org. Chem. 30, 3527. Aguiar, A. M., Archibald, T. G., and Kapicak, L. A. (1967). Tetrahedron Letters 45, 4447. Alles, B. J. P., and Sultanbawa, M. U. S. (1956). J . Chem. SOC.3472. Angeletti, E., and Montanari, F. (1958). Boll. 8ci.fac. chim. ind. Bologna 16, 140. Autenrieth, W. (1887). Ber. 20, 1531. Autenrieth, W. (1889). Ann. 254, 222, 246. Autenrieth, W. (1890). Ann. 259, 332. Autenrieth, W.(1896). Ber. 29, 1639. Backer, H.J., and van Oosten, R. P. (1940). Rec. Trav. Chim. 59, 41. Backer, H. .J., Strating, J., and Hazenberg; J. F. A. (1953). Rec. Trav. Chim. 72, 813. Bantysh, A. N., Zel’venskii, Y. D., and Shalygin, V. A. (1962). Zhur. Fiz. Khim. 36, 57. Beltrame, P. (1967). Personal communication. Beltrame, P., and Beltrame, P. L. (1968). cfazz. chim. ital. 98,in press. Beltrame, P., and CarrQ, S. (1961). Guzz. chim. ital. 91,889. Beltrame, P., and Favini, G. (1963). cfazz. chim. ital. 93,757. Beltrame, P.,C a d , S., Macchi, P., and Simonetta, M. (1964). J. C k m . SOC.4386. Beltrame, P., Bellobono, I. R., and FBre, A. (1966). J. Chem. SOC.( B )1165.

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Sopova, A. S., Perekalin, V. V., and Ledednova, V. M. (1963). Zh. Obshchei Khim. 33, 2143. Sopova, A. S., Perekalin, V. V., and Yurchenko, 0. I. (1964). Izv. Akad. Nauk SSSR, Otd. Khim. Nauk, 34, 1188. Stern, E. W., Spector, M. L., and Leftin, H. P. (1966). J. Catalysis 6, 152. Stirling, C. J. M. (19648). J. Chm. SOC.5856. Stirling, C. J. M. (196413). J. Chem. SOC.5863. Stirling, C. J. M. (19640). J. Chem.SOC.5875. Stockel, R. F., Beachem, M. T., andMegson, F. H. (1964). Can.J. Chem. 42,2880. Stockel, R. F., Beachem, M. T., and Megson, F. H. (1965). J. Org. Chem. 30,1629. Chim. France 1345. Sturtz, G., (1967). Bull. SOC. Sullivan, R., Lacher, J. R., and Park, J. D. (1964). J. Org. Chem. 29, 3664. Tarrant, P., and Warner, D. A. (1954). J. Am. Chem. SOC.76, 1624. Tarrant, P., Savory, J., and Iglehart, E. S. (1964). J. Org. Chem. 29, 2009. Taylor, D. R. (1967). Chem. Rev. 67, 317. Theron, F. (1967). Ph.D. Thesis, University of Clermont-Ferrand. Thompson, W. L. (1955). Ph.D. Thesis, Cornell University. Trofimenko, S. (1963).J. Org. Chem. 28, 3243. Truce, W. E. (1961). I n “Organic Sulphur Compounds”, Vol. 1 (N. Kharash, ed.), p. 112. Pergamon, London. Truce, W. E. (1967). Personal communication. Truce, W. E., and Boudakian, M. M. (1956a). J. Am. Chem.Soe. 78,2748. 78,2752. Truce, W. E., and Boudakian, M. M. (1956b). J. Am. Chem. SOC. Truce, W. E., and Brady, D. G. (1966). J. Org. Chem. 31, 3543. Truce, W. E., andKassinger, R. (1958a). J. Am. Chem.Soc. 80, 1916. 80, 6450. Truce, W. E., and Kassinger, R. (1958b). J. Am. Chem. SOC. Truce, W. E., and Simms, J. A. (1965). J. Am. Chem.SOC. 78,2756. Truce, W. E., Boudakian, M. M., Heine, R. F., and McManimie, R. J. (1956a). J . Am. Chem.SOC. 78, 2743. Truce, W. E., Hill,H.E., andBoudakian,M. M. (195610).J.Am. ChemSoc. 78,2760. Truce, W. E., Bannister, W., Groten, B., Klein, H., Kruse, R., Levy, A., and Roberts, E. (1960). J. Am. Chem.SOC. 82, 3799. 83, 4636. Truce, W. E., Klein, H. G., andKruse, R. B. (1961). J. Am. Chem. SOO. Truce, W. E., Rossmann, M. G., Perry, F. M., Burnett, R. M., and Abraham, D. J. (1965). Tetrahedron 21,2899. Truce, W. E., Pam, J. E., andGorbarty, M. L. (1967). Chem. & Ind. (London),660. Vessibre, R. (1959). Bull. SOC.Chim. France 1645. Webster, 0 .W. (1964). J. Am. Chem.SOC.86, 2898. Weintraub, P. M. (1966). Chem. & I d . (London) 1497. Whitlock, H. W., Jr., and Sandvick, P. E. (1966). J. Am. Chem.SOC. 88, 4525. Winstein, S., Fainberg, A. H., andGrunwald, E. (1957). J.Am. Chem.Soc.79,4146. Winterfeldt, E. (1966). Ber. 99, 450. Winterfeldt, E. (1967). Angew. Chem. (I&. Ed. Engl.) 6,423. Winterfeldt, E., and Pruess, H. (1966). Ber. 99, 450. Winterfeldt, E., Krohn, W., and Pruess, H. (1966). Ber. 99, 2752. Wittig, G. and Fritze, P. (1966). Angew. Ghem. (I&. Ed. Engl.) 5 , 846. Wittig, G., and Harborth, G. (1944). Ber. 77, 306. Yakubovich, A. Y., Sergeev, A. P., and Fogelzang, E. N. (1966). Zh. Obshchei. Khim. 36, 1317. Zugravescu, I., Ralea, R., and Petroveanu, M. (1958). Analele Stiint. Univ. A.I. Cuaa, IaaiSect. 1 4 , 181 (Chem.Abs. 1969,53, 19965).

THE REACTIONS OF HYDRATED ELECTRONS WITH ORGANIC COMPOUNDS M. ANBARl Exobiology Division, Ames Research Center, N A S A , Moffett Field, California 94035, U.S.A. I. Reactions of Hydrated Electrons with Different Functional Groups . . A. Saturated Hydrocarbons, Alcohols, Ethers and Amines . B. Alkenes C. Carbonylic Compounds . D. Haloaliphatic Compounds E. Other Electrophilic Functional Groups on Aliphatic Compounds . F. Aromatic Compounds G. Heterocyclic Compounds . H. Organic Free Radicals . I. ConcludingRemarks 11. Radiobiological Implications of the Reactions of Hydrnted Electrons with Organic Compounds A. Carbohydrates, Fatty Acids and Steroids . B. Amino Acids and Peptides C. Polypeptides and Proteins D. Purines, Pyrimidines and Nucleic Acids . . 111. Mechanism of the Reactions of Hydrated Electrons with Organic Compounds A. The Energy of Activation of the Reactions of Hydrated Electrons B. The Primary Products of eTq Reactions . C. The Merhnnism of Electron Transfer . IV. Conclusion . References .

.

. .

.

.

.

.

. .

.

.

. .

117 117 118 119 124 126 128 131 134 135 136 138 139 139 140 141 142 143 144 148 148

THE discovery of hydrated electrons in the radiolysis of water is undoubtedly one of the outstanding events in chemistry in this decade. Hydrated electrons have been found to react with many organic compounds in aqueous solution, and the kinetics of the reactions have been measured. From these kinetic studies, as well as from the detection of intermediates and the identification of final products, sufficient information has accumulated to allow a comprehensivediscussion of the mechanisms of these reactions. Hydrated-electron reactions are, by definition, electron-transfer processes, which are not very common in classical organic chemistry. The kinetic studies have shown, however, that the electron behaves analogously to a classical nucleophilic reagent and, although this analogy On leave from The Weizmann Institute of Science, Rehovoth, Israel. Present address: Stanford Research Institute, Menlo Park,California 94026. This work has been carried out at the NASA Ames Research Center, Moffett Field, California, where the author, on leave from the Weizmann Institute of Science, was a senior research associate of the National Research Council, the National Academy of Sciences, Washington, D.C. 115

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M . ANBAR

does not imply an analogous transition state, it has most interesting bearings on the electronic structure of organic compounds and their electron affinities. The understanding of the reactivity of hydrated electrons toward organic compounds in aqueous solutions is important in the interpretation of the radiolytic and photolytic behaviour of aqueous systems containing organic solutes, including living systems. This reason alone makes it worthwhile to study the reactions of hydrated electrons, but my feeling is that these reactions are more important because they may contribute to the understanding of the reactivity and electronic structure of organic compounds in general. The chemistry of organic compounds is far more methodical than inorganic chemistry. The physicochemical properties of organic compounds in homologous series change more or less systematically. It is therefore possible to predict the chemical behaviour of a given organic compound by analogy and extrapolation from the known properties of other compounds. The studies of reactions of hydrated electrons with organic compounds have been, therefore, studies of homologous series. The reactions of hydrated electrons with organic compounds appear to be mediated by specific functional groups, and it is the reactivity of these groups that determines the rate of the eCq reactions. This approach produced some quantitative correlations between the reactivity and the electron density in the reactive functional groups. This interpretation is, however, an oversimplification, and it seems more reasonable to assume that the reactivity of a given molecule is a function of its overall electron affinity. Although at first approximation the electron seems to become incorporated at a certain site on the acceptor molecule, the electronic and vibrational configurations of the primary product evidently readjust within < sec to a non-excited rearranged molecule that has accommodated the additional electron. Since all the reactions studied are exoergic, this rearrangement is accompanied by release of energy, most probably of a radiationless type, and it results in the formation of the so-called ‘ primary ” product. With very few exceptions, organic compounds do not form stable products following single-electron transfer reactions ; thus, as a rule, the “primary” products are unstable organic radical anions or radicals. The final products of the eLq reaction8 will therefore be the result of subsequent reactions of these “primary ” products. The experimental methods used in the investigation of the hydrated electron include competition kinetics and product analysis, as well as pulse-radiolysis and flash-photolysistechniques. All these methods have

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been described comprehensively in recent reviews (Dorfmann and Matheson, 1965; Hart, 1966; Walker, 1967); they will not be discussed here. The reactions of organic compounds have also been discussed in the same reviews as well as in an earlier review by the author (Anbar, 1965),but the large amount of new information that has accumulated in recent years gives us a much better insight into these reactions and their mechanisms, and requires a revision of some of the earlier theories. The reactions of hydrated electrons with the different types of organic compounds will be discussed from the standpoints of chemical reactivity and the identity of the primary products, following the classical pattern of functional groups. From this information we shall try to derive the most plausible mechanisms of these reactions.

I. REACTIONS OF HYDRATED ELECTRONS WITH DIFFERENT FUNCTIONAL GROUPS A. Saturated Hydrocarbons, Alcohols, Ethers and Amines Saturated hydrocarbons are non-reactive toward eCq (Hart et al., 1964b), as are also their hydroxy and amino derivatives. We define a compound as “non-reactive” if its rate of reaction with eap is comparable with or less than that of the (eZq+H2O) reaction. The rate of “slow” reactions (proceeding with apparent specific rates of the order of lo6 M - ~ sec-l or less) may easily be overestimated because of the presence of reactive trace impurities. Methanol and ethanol are non-reactive, and the estimated upper ~ respectively (Anbar limits of their specific rates are lo3 and 20 M - sec-l, and Hart, 1964a; Feldmann et at., 1965). Ethers are also probably nonreactive toward eCq, as may be inferred from the measured low reactivities of diethyl ether (Hart et al., 196413) and furan (Szutka et al., 1965). The reactivity of polyhydroxy alcohols toward eLq has not been investigated to date, but from the measured reactivity of sugars it may be inferred that they are non-reactive. The (low)reactivity of sugars may be attributed solely to their carbonylic functional group ; glucose, ribose and arabinose were found to react with eZq at rates lower than lo6 M - ~sec-l (Davis et al., 196513; Phillips et al., 1966). The non-reactivity of amines may be deduced from the behaviour of the potassium-ethylenediaminewater system (Dewald et al., 1963), in which the hydrated electrons formed have been shown to disappear at a rate comparable with that of the (egq+ H,O) reaction in pure water. It may be concluded that organic compounds composed only of H, C, 0, and N atoms, and containing no wbonds, are non-reactive toward e&

118

M. A N B A R

B. Alkenes The reactivity of a C=C double bond is rather low, as can be seen from the rate of reaction of ethylene (k< 2.5 l o 6 M - - ~sec-l) (Cullis et al., 1965). Electron-donating groups, such as OH, make the ethylenic bond even less vulnerable for electron acceptance, as can be concluded from the non-reactivity of vinyl alcohol and pyrrole (Szutka et al., 1965; Scholes and Simic, 1964). Electron-withdrawing groups enhance the reactivity of ethylene derivatives; thus methacrylate, fumarate and maleate ions are found to react at a rate close to the diffusion-controlledlimit (Hart et al., 1964b). Maleate monoanions as well as tetracyanoethylene react at diffusioncontrolled rates (k> 10’O M-’ sec-l) (Hart et al., 1964b). The conclusion that the ethylene bond acts as the main electrophilic centre in the latter cases is based on the fact that acetate ions are non-reactive, and nitriles react at rates more than two orders of magnitude lower than the diffusioncontrolled limit (Anbar and Neta, 1967a). Replacing R in RCH=CH2 by an ester, amide or olehic group (R = CO .OR; CO .NH2, CH = CH2) enhances the reactivity of the ethylene functional group up to the diffusion-controlled limit, as can be seen from the reactivities of ethyl fumarate, acrylamide and butadiene (Hart et al., 1964b). A comparison of these compounds with ethyl acetate and acetamide, which are only moderately reactive (Anbar and Neta, 1967a), corroborates the assignment of the ethylenic function group as the main electrophilic centre. The high reactivity of cinnamate ions and of styrene, both of which react at diffusion-controlledrates (Hart et al., 1964b; Szutka et al., 1965), is due to the effect of the phenyl group on the C=C functional group, since both toluene and phenylacetate ions react a thousand times slower (Anbar and Hart, 196413). Most of these “activated” ethylene compounds react at diffusioncontrolled rates. It is therefore impossible to derive any quantitative correlation between the electron-donating capacity of the adjacent groups and reactivity. The products of the (e,+RCH=CH,) reaction are RCH-CH; carbanions. Some of these have been identified by their chemical reactivity. Others have been observed through their absorption spectra by means of pulse-radiolysis techniques. The carbanion of acrylamide, for instance, has been shown to dimerize, to react with other free radicals, inducing anionic polymerization, and to react with oxygen, Ag’ and Fe(CN)g- ions, presumably by electron-transfer reactions (Chambers et al., 1967). The absorption spectrum of the product of the (dimethyl fumarate + e&) reaction has been observed in alkaline solution. The rate

T H E REACTIONS O F HYDRATED ELECTRONS

119

of reaction of this species with oxygen has been measured and found to be almost diffusion controlled (Adams et al., 1967b).

C. Carbonylic Compounds The carbonyl group is highly reactive toward eTq, but its reactivity is strongly influencedby adjoining groups. For example, the rate constants decrease by four orders of magnitude when the methyl groups of acetone are replaced by amino groups. The effect of the substituents R and R’ on the reactivity of R . CO .R‘ has been correlated with their Taft u* values (Hart et al., 1967). This correlation included aldehydes (R=H), ketones (R=CH3), carboxylic acids (R=OH), amides (R=NH2) and esters (R=OR). Since the values for R and R’ are additive, the rates of reaction have been correlated wih (ug+ &.). For aldehydes, ketones and carboxylic acids, the reactivity of the compound was found to decrease with the electron-withdrawing capacity of R and R’, and a linear correlation was found between logk and (ud + ud,)with a negative slope of 0.74 for a range of rates over two orders of magnitude from cyclohexanone to pyruvonitrile. The effect of R and R’ on the rates is directly correlated with their effect on the C=O bond length, as manifested by the change in u(C=O) stretching frequency. As the C=O bond is shortened, the electron density in the r-orbital increases, resulting in a decreased tendency to accommodate an additional electron. Amides and esters exhibit a different dependence of their rates on the electron-donating capacity of the adjacent groups. In this case electronwithdrawing groups enhance the rate of reaction. A linear correlation between logk and (u*+ cr*) is observed, with a positive slope of 1.2. This behaviour has been attributed to the mesomeric effect of these substituents, which can also be inferred from their effect on u(C=O). The mesomeric forms R

\c-os-

H2N8+/

and R \C-O8-

ROsf’

depress the double-bond character of the C=O group. This makes the carbonyl bond non-reactive towards eLg, and creates a new electrophilic centre of somewhat lower reactivity. The mesomeric form of esters R’

‘c-o-

R20+/

120

M. ANBAR

although non-reactive at the carbonyl bond, has a finite electron affinity at the alkoxy oxygen. This electron affinity will increase with the electron-withdrawing capability of R1. The reactivity of RlCO .OR2 esters toward eTq correlates with an increase in u* of R1; there is a hundredfold increase in reactivity from (CH,),C. CO. OCH, (u*= 1.15) to CF,.CO.OCH, (u*=3.03). The reactivities of formamide and acetamide seem to be due to the R

\COa-

HzW+/

mesomeric form, and they fit satisfactorily on the same (logk - u*)curve as the esters (Hart et al., 1967). The reactivity of the carboxylic acids HCO.OH, CH,.CO.OH, O-OC(CH2)2.C0.0H and (CH,),C.CO.OH seems to depend both on the inductive and mesomeric effects (Hart et al., 1967). The reactivity of eyq with carboxylic acids has also been interpreted in terms of a Brlansted relationship (i.e., taking the hydroxylic hydrogen as the reactive centre) with reasonable success (Rabani, 1965). Following this correlation one would, however, predict succinic acid (pK,=5.6) to be considerably less reactive than acetic acid ( p K a= 4.75) and the latter less reactive than formic acid ( p K a= 3-75), contrary to the experimental findings. It may be concluded, therefore, that the proton-donor capacity of carboxylic acids is not a primary factor in their reactivity towards cap. The substitution of an a-hydrogen on a carboxylic acid by an aminogroup decreases the reactivity. The rate constants of glycine and alanine are 8 x 10"and 6 x 10"M - ~sec-l, respectively (Davis et al., 1965a). This low reactivity of amino acids is expected because they are predominantly in the form of a zwitterion. Other amino acids exhibit higher reactivity, owing to other reactive functional groups (Braams, 1965, 1966). Peptides show a significantly higher reactivity than amino acids (Davis et al., 1965a; Braams, 1967). This reactivity was suggested to be due primarily to the ammonium functional group and not to the carbonyl group of the peptide. This conclusion was inferred from the comparison between the reactivities of acetyl-glycine and glycyl-glycine, which differ by an order of magnitude, as well as from the pH dependence of the reactivity of the latter compound. Further, a linear correlation between the logarithms of the dissociation constants of the ammonium groups of amino acids and dipeptides and the logarithms of the specific rate constants has been demonstrated (Braams, 1967). This correlation, ranging over four orders of magnitude in rate, has a slope of 0.8. It should be noted, however, that the product of reaction of eyq with the

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acid forms of amino acids is ammonia (Garrison, 1964; Adams and Michael, 1967) and not hydrogen atom as might have been expected according to Rabani from his Brcansted relationship (Rabani, 1965). It may be suggested that the reactive centre of amino acids and peptides is the carbonylic group, which is activated toward a nucleophilic attack by the adjacent ammonium group. The higher the pK value of this group, the smaller is its inductive effect on the carbonylic functional group. This puts the reactivities of amino acids and peptides in line with the behaviour of esters and amides, as expected from the general behaviour of carbonylic compounds. The a*-correlation for carbonylic compounds suggested by Hart et al. (1967) can be applied to additional compounds ; thus, 2-ppolidone (k= 1.3 x lo7 M-' sec-l) (Szutka et al., 1965), asparagine in alkaline solution (k= 2.4 x lo'), acetylglycine and acetyl-alanine at pH = 9 (k lo7M - ~sec-l) (Braams, 1966) react at a rate practically equal to that of acetamide (k= 1.7 x lo7M - ~sec-l) (Hart et al., 1967). The ring closure seems to have little effect on the reactivity of the carbonylic group. Urea (k< 3 x lo6 M - ~sec-l) (Hart et al., 1967) is less reactive than expected according to log k - u* correlation. This has been explained by the fact that urea may be represented by the electronic structure N

which lacks any well-defined electrophilic centre. Consequently, a very low reactivity is expected. On the other hand, oxamate ions react significantly faster than expected (Hart et al., 1967). The stabilization of the mesomeric form of the oxamate ion by hydrogen bonding may probably account for the high reactivity of this compound. The oxamate ion may exist in the forms :

Hydrogen bonding stabilizes the carbonyl group on the carboxylate ion, thereby providing the oxamate ion with two highly reactive electro-

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M. ANBAR

philic centres. This assumption may explain the high rate constant (4 x l o 9 M - ~sec-l) for this compound. It is interesting that p-benzoquinone,

reacts at a lower rate than acetone (k= 1.4 x lo9 M - ~sec-l) (Hart et al., 1964a) despite the conjugation of the system and its relatively high oxidation potential. A possible explanation may be the strong inductive effect of the C=C bonds, which shortens the C=O bond and simultaneously increases the electron densities in the C=C and C=O double bonds. This is one of the few cases in organic chemistry when a statement may be made about a correlation between redox potentials and eCq reaction rates, and it seems that, as in inorganic chemistry (Anbar, 1968b), these two parameters are not always directly correlated. Although they are not carbonylic compounds, carboxylate ions should be discussed here in conjunction with the carboxylic acids. Owing to its resonance stabilization, the -COT group has no low-lying vacant orbital or any positive electron affinity; thus it is non-reactive toward eLq. Carboxylate ions with aliphatic chains, which may also carry OH or NH2 groups, are evidently non-reactive. This has been shown in the cases of formate, acetate, citrate, lactate, oxalate, glycinate and ethylenediaminetetra-acetate ions, all of which react with eLq at rates lower than l o 6 M - ~sec-l (Anbar and Neta, 1967a). Oximes behave analogously to carbonyls in their reactions with eLq, and their log k versus u* plot has a comparable p value. Their reactivity is somewhat lower than that of ketones ; for example, acetoxime reacts at a rate of 3.0 x los M - ~sec-l, compared with 6 x l o B M - ~sec-l for acetone, and acetaldoxime (k= 7.2 x l o 7 M - ~sec-l) is less reactive than acetaldehyde (k= 3.5 x lo9 M - ~sec-l) (Hart et al., 1964a, 1967). The lower reactivity of the oximes may be partially due to the inductive effect of the OH group on the nitrogen atom. This effect lowers the dipole moment from 1.3 Debye units (D) for propylamine to 0.9 for acetoxime. By contrast, the dipole moments increase from 1.6 D for propan-2-01 to 2.9 for acetone. The primary product of the reaction eLq+ R1.CO .R2is (R'. CO. R2)-. This is a strong base and will react with water to give a R'R260H

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123

radical (Gordonetal., 1964;Kevanetal., 1964; Adams et al., 1964, 1967a). These species have been demonstrated by flash radiolysis or electron spin resonance (E.S.R.) for several carbonyl compounds. The equilibrium constant for the reaction (CH,. CO .CH3)- + HzO -+ CH, .&OH.CH, -t OH- has been determined (pK= 12.2) (Asmus et al., 1966b). The value is consistent with previous findings that the transient in alkaline solution is identical with the primary product formed from isopropanol by hydrogen abstraction. The predominance of CH,. CO .CH, in alkaline solution may also be deduced from its reactivity in this medium (Adams et al., 1967a). The analogous transients of acetophenone and fluorenone have been observed (Adams et al., 1964,1967b) as well as that formed from thiobarbituric acid (Gordon, 1964). The negative-ion derivatives of acrylamide, methacrylamide and acrylonitrile may be considered as further CO. R2)- (Dainton, 1967). The electron transfer from examples of (RI. (CH, .CO .CH,)--to acetophenone has been found to proceed at a rate of 8 x lo8 ~ - s e c - l(Adams et al., 1967a). Thesamespecieshasbeenfoundto react efficiently with bromoacetate and bromopropionate ions, and this reaction, which is probably an electron-transfer process, results in a quantitative debromination of the bromaliphatic compounds (Anbar and Neta, 1967~).The electron adduct of benzoquinone was found to react very rapidly with water to form the semiquinone (Adams and Michael, 1967). The primary products of the reactions with ketones probably undergo disproportionation to give the parent compound and the corresponding secondary alcohol. 2(R1.C0.R2)- -+ R1.C0.R2+R1.6HOH.R2+20H-

The primary products of carboxylic acids decompose in two parallel first-order processes (Thomas, 1964; Hart, 1964; Anbar, 1965). (RCO.OH)- ----+ RCO.0- + H

There is little information on the chemical fate of the intermediates formed from esters and amides in the reactions with eLq. It is suggested that they decompose to give acyl radicals : (R1.CO.OR)- -+ R1.CO+R20R1. CO .NH2 R1.CO +R'.CO +HzO

-+ R1.CO + NH, --f

R2.CO .OH+RIC€IO

124

M. ANBAR

The acid forms of amino-acids have been shown (Garrison, 1964; Willix and Garrison, 1967; Ayscough et al., 1967) to decompose according to RCH(NHs+).COz-+ e- -+ RCH(NH3).COZ- -+ R C H . COz-

+ NH3

Peptides were also suggested to undergo deamination following the incorporation of an electron (Willix and Garrison, 1967). I n summary, carbonylic compounds are electrophilic reagents and practically all such compounds investigated exhibit a measurable reactivity toward eTq. The reactivities of these compounds strongly depend on the inductive and mesomeric effects of the adjacent groups. The inductive and mesomeric effects on certain reactive centres may also be considered as effects on the overall electron affinity of the molecules, which is a function of the energy level of the lowest vacant orbital. The ultimate fate of the substrate after having accommodated an additional electron depends on its chemistry and, in particular, on the dissociation energy of the RCO-X bond, which determines whether (RC0X)- will undergo dissociation or electron transfer.

D. Haloaliphtic Compounds Fluoroaliphatic compounds have been found to be non-reactive towards eZq, as can be seen from the behaviour of fluoro- and trifluoroacetate ions (Anbar and Hart, 1965a). The same conclusion may be inferred from the behaviour of trifluoroacetone and methyl trifluoroacetate (Hart et al., 1967),the reactivity of which has been shown to be fully accounted for by that of the carbonylic functional group. An organically bound fluorine atom does not act as an electrophilic centre, in accord with the high electronegativity of fluorine, resulting in entirely occupied low-lyingorbitals on the fluorine atom. Organicallybound fluorine resembles, therefore, the hydroxylic oxygen, the amino nitrogen and the saturated carbon atoms, all of which have their lowlying orbitals completely filled. Chloro-, bromo- and iodo-aliphatic compounds have been investigated for their reactivity towards eZq(Szutka et al., 1965) and the results have been interpreted by assuming that the halogen atom is the reactive electrophilic centre (Anbar and Hart, 1965a). I n all homologous halocompounds the order of reactivity is F 4C1< Br < I. The relative reactivities of the four monohalo acetates are 2 x 1:5 : 10. The reactivity of a given halogen atom was found to be increased by the inductive effect of adjacent electron-withdrawing groups and to decrease by adjacent electron-donating groups. A quantitative examination of the

THE REACTIONS O F HYDRATED ELECTRONS

125

kinetic data has shown that the inductive effect of the adjacent group on the reactivity of a given halogen atom is satisfactorily represented by Taft’s o* function. The specific rates of chloro-aliphatic derivatives range from 4 x lo8 M - ~ sec-l for compounds carrying a deactivated chlorine atom, e.g. chloroethanol, to the diffusion-controlledCF,Cl, an activated chloroderivative (Anbar and Neta, 1967a). Polychloro-derivatives, e.g. CHCl, or CCl,, react at diffusion-controlled rates (k= 3 x 1O1O M - ~sec-’) (Hart et al., 1964a). This is expected in view of the inductive effect of adjacent chlorine atoms in addition to the statistical factor in polychloroderivatives. It has been pointed out that the reaction cross-sections of CC14 and CHCl, are significantly larger than the “geometrical ” dimensions of these molecules, a result that strongly suggests electron tunnelling (Anbar and Hart, 1968). Bromo-aliphatic compounds behave similarly to their chloroanalogues, and their specific rates range from 1.6 x l o QM-’ 8ec-l for deactivated bromoethanol to diffusion-controlledrates. Iodo-derivatives react with eLq at diffusion-controlled rates (Anbar and Neta, 1967a). Chloroaliphatic compounds have been shown to undergo quantitative dechlorination on reaction with e , (Hayon and Allen, 1961; Stockdale and Sangster, 1966). Bromo- and iodo-derivatives follow a similar pattern (Anbar, 1965; Anbar and Neta, 1967c). This dehalogenation is not a result of a dissociative electron capture RX+e- --+ R + X -

which generally is an endothermic process (Anbar, 1965), but is due to the decomposition of an intermediate : RX+e,

--+ RX- + R + X -

Evidence that the cleavage of the R X bond does not take place in the rate-determiningstep could be derived from the absence of a solvent effect on the rate of eTq+ RX reactions (Anbar and Hart, 1965a) and from the fact that the activation energy of the (eLq+ RX) reaction is the same for compounds with quite different R-C1 bond strengths (Anbar and Hart, 1967). The decomposition of RX-, which is probably a very fast reaction, is induced by the solvation of X- and may be regarded as a typical SN1process. The existence of RX-, which is an analogue of X: (Anbar and Thomas, 1964),has been inferred from the kinetic behaviour or radiolysed chloroaliphatic compounds (Logan and Wilmot, 1966). Convincing evidence

126

M. ANBAR

for the formation of CH,Br- in the gas phase has been advanced (Johnson and Simic, 1967),and the formation of CH,I- as intermediate could help to explain the behaviour of other systems. The formation of CClT in the gas phase was also postulated (Reed, 1962). Although the lifetime of CH,I in aqueous solution has been shown to be shorter than lo7 sec, this does not exclude its existence as a short-lived intermediate (Thomas, 1967). No direct observation of RX- by pulse-radiolysis or flash-photolysis techniques has been achieved to date. RX- and especially RCI- are expected to be demonstrable by nanosecond pulse techniques. Unlike IT or CI,, the dissociation of RX- will be irreversible, since the organic free radical formed on dissociation will rearrange within < sec to a configuration that will not interact with X-. The only organically bound, pseudohalogenic group that has been studied to date is the cyano-group. It seems to have some electrophilic reactivity, as can be seen from the reactivities of cyanoacetate (k= 4 x lo7 M - ~sec-l), acetonitrile (k= 3.0 x l o 7 M - ~sec-l) and propionitrile (k= 1.5 x lo8 M - ~sec-l) (Anbar and Neta, 1967a). The reactivity of CN as an electron-accepting group may be placed somewhere between fluorine and chlorine, which is in accord with its inductive effect, manifested in the pK values of the corresponding monosubstituted acetic acids. There is no information on the primary or secondary products of these reactions. I n view of the C-C bond strength and the relatively low solvation energy of cyanide ions, it seems reasonable to assume that H RCN radicals will be formed as secondary products. RCN-+HzO

--i’

H RCN+OH-

These will then disproportionate to give RCH=NH, which in turn will hydrolyse to give aldehydes. The reduction of nitriles to aldehydes by eZq awaits experimental verification.

E. Other Electrophilic Functional Groups on Aliphatic Compounds No systematic study has been made to date on electrophilic functional groups of aliphatic compounds other than the carbonylic group and the halogens. The kinetic behaviour of sulphur-containing compounds is too inconsistent to allow far-reaching generalizations. It seems that RSH compounds are highly reactive in neutral solutions (pH = 6-7) and approach the diffusion-controlledlimit. This is true of cysteine, penicil-

THE REACTIONS O F HYDRATED ELECTRONS

127

lamine, cysteamine (Braams, 1966),and methyl mercaptan (Armstrong and Wilkins, 1964). RS- in alkaline solution (pH > pK) is significantly less reactive. Cysteine, HS. CH2.CH(NH,) .COO, (k= 7.5 x lo7 M - ~ sec-l), thioglycollate ions (k= 8-2 x l o 7M - ~sec-l), glutathione (k= 3.2 x 10” M - ~sec-l at pH = 6.4) and thiophenolate ions at pH = 11 (k= 4.7 x lo7) are representative examples (Anbar and Neta, 1967a). Thioethers R1SR2 show a reactivity comparable with that of RS-. Methionine, CH,S .CH, .CH2.CH(NH,). CO .OH, reacts at a rate of 3.5 x lo7 M - ~ sec-l and djenkolate ions (3,3’-methylenedithio-bis-2-aminopr~pionate) react at a comparable rate (Braams, 1966). Disulphides RSSR are highly reactive, the rates of most of them, like cystine, homocystine, oxidized glutathione and cystamine, approach the diffusion-controlled limit (Braams, 1966). Thiocarbonyls are highly reactive, as can be seen from the reactivity of thiourea (k= 3 x loQ)(Charlesby et aZ., 1965). It may be stated that, generally, the sulphur compounds are far more reactive than their oxygen homologues. Transient products of sulphur-containing compmnds have been observed in the cases of cystine (Adams et aZ., 1967a) and thiourea (Charlesby et al., 1965). It has been shown that RSSR- undergoes a reversible dissociation RSSR-

+ RS+RS-

( k = 1.2 x 104 M-1

sec-1)

followed by RSSRS -+ RSSR

whereas in acid solution RSSR-+H+

+ RSSRH

+ RS+RSH

I n the case of thiourea it was suggested that the free radical formed by a reaction with water, (NH,),CS- -+ (NH,),CSH + OH-, acts as a hydrogenating agent toward polyethylene oxide (Charlesby et al., 1965); however, an electron-transfer mechanism from (NH2),CS- cannot be excluded. Another highly reactive functional group is the nitro-group. All RNOz compounds examined approach the diffusion-controlled rate limit (Anbar and Neta, 1967a). A closer examination shows that the reaction cross-sections of trinitromethane and trinitromethyl ions are higher than the “geometrical ” dimensions of these molecules, implying electron tunnelling (Anbar and Hart, 1968). Nitromethane and its anion CH2N0, react with eTq at diffusion-controlled rates (k= 2.1 and 0.66 x 10” M - ~sec-I, respectively) to give CH,NO,, which has been observed

128

M. ANBAR

by pulse radiolysis. This species is a weak acid (pK= 4.4) capable of electron transfer to tetranitromethane at a very fast rate (fc = 1.2 x l o 9 M - ~sec-l) (Asmus et al., 1966a). It might be of interest to investigate the reactivity of additional functional groups by examining organic cyanates, thiocyanates , selenides, tellurides, phosphines, arsenides and others. All these compounds, which are expected to be reactive towards eTq, await investigation that may help to evaluate their electron affinities.

F. Aromatic Compounds The study of the reactivity of e , towards an extensive series of monosubstituted benzene derivatives CeH6X revealed the first linear freeenergy relation for reactions of hydrated electrons (Anbar and Hart, 1964b). The specific rates of these reactions ranges over four orders of magnitude from 4 x lo6 M - ~see-l for phenol to 3 x 1O1O M - ~sec-l for nitrobenzene. The specific reaction rates of substituted benzenes with eLqhave been related to that of benzene and expressed in terms of r ) values, where r ) =log ( k C s H s X / k C s H s H ) . Comparable values of r) are obtained for monosubstituted toluenes and phenols. The r ) values, indicating the relative reactivity of an aromatic system carrying a given substituent, have been correlated with the effect of the same substituent on the reactivity of these systems towards nucleophilic or electrophilic reagents. A quantitative evaluation of these effects has been achieved by the use of Hammett’s pu equation, log (kCeHsX/ kCeH,)=po. When the r ) values were plotted against the u values compiled by Van Bekkum et al. (1959),a satisfactory correlation was obtained for all substituents studied ( p = 4.8), with the exception of bromine and iodine. Both bromo- and iodo-benzene derivatives show a higher reactivity than expected from the effect of these substituents on the electron density in the ring. This specific effect is probably due t o the additional electrophilicity of the carbon-bound halogen atoms that has been manifested in the haloaliphatic compounds. It seems that the electron-donating capacity of the nucleus of chlorobenzene or chlorobenzoate ions practically eliminates the electrophilicity of the bound chlorine. A series of para-derivatives of benzoic acid was examined for their rates of reaction with eLq, and their q values, relative to benzoic acid, were calculated. These r ) values are proportional to the u values of the monosubstituted benzene series, and p = 0.74 was found for the benzoate series. The behaviour of the benzoic acid series shows that in contrast to

THE REACTIONS O F HYDRATED ELECTRONS

129

aromatic substitution reactions, u values of different substituents are not additive; however, a constant p is obtained for a homologous disubstituted series in which one substituent is kept constant and the other is being changed. The higher the rate constant of the monosubstituted parent compound, the lower will be the p values of the series. A molecule, CBHBX, that has a high probability of accepting an electron, will be affected to a lesser extent by an additional substituent. The smaller p values observed in the more reactive series may also be anticipated in view of the fact that the rate of these reactions approaches the diffusion-controlled limit, 1O1O M - ~sec-l, where a further increase in rate is impossible. Surprisingly similar results are obtained when monosubstituted benzenes react with solvated electrons in methanol ( p = 4.7) (Sherman, 1966). This result, which is in accord with other cases examined both in H20 and MeOH (Anbar and Hart, 1964b), suggests that the rates of e;; reactions are independent, at first approximation, of the dielectric constant of the solvating medium and of its viscosity. The implication of this finding will be discussed in Section 111. The erqrate constants correlate better with “normal ” u values derived from electrophilic substitution than with cr “para” values obtained from data of nucleophdic reactions. This is not surprising in view of the fact that the eLq reactions constitute an interaction of an electron with the .rr-orbitalsof the ring, as in electrophilic substitution, rather than with effects on electron distribution and polarizability of a certain substituent. It should be remembered, however, that the “classical” treatment, which tries to describe the behaviour of a molecule by the combined action of a number of parameters, is just an oversimplification. It is plausible that the u function is correlated with the gain in free energy on addition of an electron to a given aromatic compoundin aqueous solution, which is, in turn, a major factor in eCq reactions. Reliable information on the electron affinitiesof these compounds in the gas phase would be helpful. It should be mentioned here that a semiquantitative agreement is observed between the reactivities of aromatic compounds with eLq and rough values of their electron affinities in the gas phase (Lovelock, 1961). The primary product of the reaction PhR + eTq is the PhR- anion. This species may undergo one of three reactions : N

P h X - --• Ph+X-

PhX-

Ha0 --+

PhXH+OH-

P h X - + Y --+ PhX+Y-

(Anbar et at., 1967) (Sangster, 1966)

(Adams et nl., 1967b, Arai et aZ., 1967)

130

M. ANBAR

-

These may be followed by PhXH

Ph+XH

Ph+Ph + (Ph)z PhSH +PhSH

__f

\

PhSHz + PhX (PhSH)s

(Land and Ehort, 1967)

Transient PhX-or PhXH has been observed by pulse radiolysis in the cases of benzene (Guarino and Hamill, 1964), benzaldehyde (Chutny, 1967), benzoic acid (Sangster, 1966), trimesic acid (Gordon, 1964), phthalic acids (Gordon et al., 1964), p-naphthol (Gordon, 1964), nitrobenzene and benzonitrile (Chutny, 1967),phenol (Land and Ebert, 1967), trinitrophenol (Gordon, 1964),and acetophenone and fluorenone (Adams et al., 1967b). There is not sufficient quantitative information on the rates of the secondary dissociation and protonation reactions. The rate of PhR- + H,O+is probably diffusion-controlled,as may be inferred from the analogous reaction in alcohols (Arai and Dorfmann, 1965). The reaction PhR- + H20 + PhRH + OH- is much slower and, by analogy to the reaction of alcohols, the first-order rate constant may be estimated to be about lo7sec-l. This is still too fast for observation by microsecond techniques (Sangster, 1966). It may be of interest to investigate these reactions by nanosecond techniques, especially when it is possible to distinguish between ortho-, meta- and para-derivatives of the cyclohexadienyl radicals produced. This may add information on the electron distribution within the carbanionic aromatic molecules. The lifetimes of some of these carbanions may be limited by their dissociation to a phenyl radical and a stable anion. This pattern of reaction has been demonstrated in the eTQ-inducedquantitative deiodination of the iodobenzoic acids, as well as in the debromination ofp-bromophenol (Anbar et al., 1967). One of the few cases that has been thoroughly investigated by pulse radiolysis is the chemistry of C6H5NO;, which, unfortunately, is not a typical aromatic carbanion. This ion radical has the electron attached t o the nitro-group, and on protonation C6H6NO2His produced. This species is different from the adduct formed by the reaction C6H5NO2+ H --f CBH6NOz(Asmus et al., 1966~).C6H5N02Hwas found to be a relatively weak acid (pK = 3.2) that undergoes disproportionation to give nitrobenzene and C6H5N(OH)2. The latter species undergoes dehydration to give nitrosobenzene. On the other hand, C6H5N0, is relatively stable and transfers its excess electron to C6H5N0 at an appreciably fast rate (k=4.1 x 10' sec-I). An analogous

THE REACTIONS O F HYDRATED ELECTRONS

131

system studied is the reaction C6H6N0+ eLq --f C6H6NO- followed by C6H5NO- H+ + C6H5NOH(Asmus et al., 1966a). Several reactions of aromatic compounds have been investigated for their energies of activation. These include p-bromophenol, phthalate, benzoate, benzensulphonate ions, benzyl alcohol, phenylalanine and phenyl acetate, the specific rates of which range from 3-7 x 10' to 1.2 x 1O1O M - ~sec-l. The energies of activation of all these reactions were found to be the same, namely, 3-5 & 0.5 kcal mole-l (Anbar et al., 1967). This corroborates the conclusion that the rate-determining step in eTqreactions with aromatic compounds involves one and the same process, namely, the accommodation of an electron into the aromatic substrate. The subsequent reactions discussed above may be fast or slow but are not involved in the rate-determining step of the reaction of the hydrated electron.

+

G. Heterocyclic Compounds The reactivity of heterocyclic compounds towards eLq can generally be deduced from the chemical behaviour of the aliphatic and aromatic systems discussed in the previous Sections. Thus one finds, for instance, that pyrrolidine (1) (tetraethyleneimine) (Szutka et al., 1965)and proline

(2) in alkaline solution (Braams, 1966) are non-reactive, like any other

amine. The slight reactivity reported for hydroxyproline (3) in alkaline solution (k= 1.1x l o 7 M - ~sec-l) (Braams, 1966) must be due to trace impurities, as it is hard to understand a difference in rate of one order of HOCH-CH2

I

I

CH2 C H . C O 2 \ /

NH

(3)

132

M. ANBAR

magnitude between proline and hydroxyproline. Interestingly enough, pyrrole (4) is also non-reactive (k= 6 x lo6 M-’ sec-l) (Szutka et al., 1965) despite the conjugated carbon skeleton. It has been suggested that the CH-CH

II

II

CH CH \ / NH

imine group donates electrons to the terminal points of the butadiene structure, thus eliminating their electrophilicity (Anbar, 1965). I n view of the behaviour of pyrrole, it is suggested that the measured rate of pyrrolidine (k=4.2 x loe M - ~sec-l) is much higher than expected and may be due to trace impurities. Analogous behaviour is observed in the case of furan (5) (k= 3 x lo6 M - ~sec-’) (Hart et al., 1964a). The latter rate constant may be considered an upper limit. Thiophene ( 6 ) is CH-CH

II

II

CH CH ‘ 0 ’

CH-CH

It

CH S ‘’

/I

CH

somewhat more reactive as expected for a thioether ; however, its reactivity (k= 6.5 x lo7 M-I sec-l) (Szutka et al., 1965)is not appreciably higher than that of methionine (k= 3.5 x l o 7 M - ~sec-’) (Braams, 1966), implying that the butadiene conjugation effect is suppressed also in this case. The effect of the NH electron-donating group in a heterocyclic system on an electrophilic centre is demonstrated again in the case of indole (7), which is significantly less reactive than styrene (k= 7-8 x l o 8 and 1-1x 1O1O M - ~sec-l, respectively) (Hart et al., 1964b). Here the

THE REACTIONS O F HYDRATED ELECTRONS

133

NH group deactivates both the ethylenic bond and the aromatic nucleus. As the reactivity of tryptophane (8) in alkaline solution (k= 1-8 x lo8 M - ~sec-l)

(Braams, 1966) is significantly lower than that reported for

indole, the measured rate of the litter may be partly due to trace impurities ;the deactivating action of the heterocyclic NH is thus even more pronounced. Imidazole ( 9 ) seems to be more reactive than pyrrole, its carbon HC-N

It

HC,

II

.,CH NH

analogue (k= 2.2 x lo7 M-* sec-l) (Braams, 1966). This is to be expected from the polarization of the C=N bond, which makes the carbon an electrophilic centre. It should be remembered, however, as has been shown in Section IC, that the C=N bond is less reactive than the C = O bond. The imidazolium ion is much more reactive (k= 4 x l o 9 M - ~sec-') (Braams, 1966) than the base. This may be explained by the strong inductive effect of the ammonium group on the >C=N- reactive centre. Histidine shows good agreement with the behaviour of imidazole; k = 3.9 x log i c l sec-l for the acid form and 1.2 x lo7 M-I sec-l for the basic form (Braams, 1966). The pK, value of imidazole (6.9) is comparable with that of HzPOr (pK=7.2), but its reactivity is over two orders of magnitude higher. This demonstrates again a protonic acid that does not fit into Rabani's Brarnsted relation (Rabani, 1965). It should be remembered that the reactivities of formic and acetic acids included in Rabani's treatment have been shown to be accounted for by their carbonylic groups. Thus the suggested Brprnsted relation may be adequate for certain inorganio protonic acids only. The higher polarity of the C=N bond and the resonance effect are probably the reason for the higher reactivity of pyridine (k= 1.0 x lo9

134

M. ANBAR

M - ~sec-') (Hart et al., 1964a). It has been pointed out that the replacement of a carbon atom of a double bond by a tertiary nitrogen atom increases the reactivity of the compound by two orders of magnitude (Anbar, 1965). This is true in the cases of pyrrole and imidazole, benzene and pyridine, as well as in the cases of thioazole and thiophene ( E = 2.5 x loo and 6-5x lo', respectively) (Anbar andNeta, 1967a). I n the case of the purines and pyrimidines, the electrophilicity of the \ ,C=Nand C=O group generally outweighs the deactivating action

of the OH and NHz groups; thus all these compounds approach the diffusion-controlled limit. Some differences in rate, like that between adenosine and adenosine-5-phosphate (3.1 x 1O1O and 3-8x l o 9 M - ~sec-l, respectively) (Scholes et al., 1965), may be accounted for by the double negative charge of the latter species. Transient products of the reactions of heterocyclic compounds with eLq have been observed for adenine, purine, cytosine, methylcytosine and thiobarbituric acid (Gordon, 1964) as well as for pyridine (Cercek and Ebert, 1967). A systematic study of the chemical behaviour of these transients is desired, as some of them may be intermediates of biochemical and radiobiological importance. H. Organic Free Radicals

It has been generally accepted that paramagnetic species react with hydrated electrons at diffusion-controlledrates (Anbar, 1965). Aliphatic radicals of the type R1R2R36(where R = H or alkyl groups) seem to be an exception to this rule. It has been shown in pulse-radiolysis studies that the product of the reaction CHBOH+ OH, namely, 6HzOH, reacts with eLq at a rate at least one order of magnitude less than that of the reaction eLq + OH. Methanol is therefore routinely added to pulseradiolysis matrix solutions to convert the reactive OH radicals to relatively inert CH20Hradicals. I n high-intensity radiolysis and photolysis experiments, methanol has been shown to remove OH radicals quantitatively without affecting the concentration of the electrons, which were subsequently converted quantitatively to hydrogen molecules by the reaction eLq + eyq