Electrophilic Bromination of Carbon—Carbon Double Bonds: Structure, Solvent and Mechanism

Electrophilic Bromination of Carbon-Carbon Double Bonds: Structure, Solvent and Mechanism MARIE-FRANCOISE RUASSE Institut de Topologie et de Dynamique des Systkmes de l’universitk Paris 7, associk au C N R S - U R A 34, 1 rue Guy de la Brosse, 75005 Paris, France

Introduction 208 Methods for obtaining reliable bromination rate constants 21 1 Kinetic rate equations 212 Kinetic techniques for bromination 214 Bromine-olefin charge transfer complexes as essential intermediates in bromination 216 The ionic intermediates: bridged bromonium ions or open B-bromocarbocations 220 Experimental observations 221 Theoretical calculations 224 Kinetic data and bromine bridging in transition states and intermediates 225 Product data and bromine bridging from stereo- and regio-chemistry 234 Kinetic substituent effects 243 Polar effects of alkyl groups 243 Steric effects of alkyl groups 246 Kinetic effects of aryl substituents 252 Selectivity relationships and transition-state shifts in arylolefin bromination 256 Early transition states in enol ether halogenation 263 Solvent effects and solvation in bromination 267 Kinetic solvent isotope effects 268 The Y,, scale for bromination 270 Values of mBr in alkene bromination: nucleophilic and electrophilic assistance by protic solvents 272 Values of mBr and transition-state shifts in the bromination of conjugated olefins 274 Bromine-catalysed bromination in non-protic and halogenated solvents 276 Solvation, the driving force of electrophilic bromination 278 The reversible formation of bromonium ions 279 Return in halogenated solvents 280 Return in protic solvents 282 207 ADVANCES IN PHYSICAL ORGANIC CHEMISTRY VOLUME 28 ISBN 0-12-033528-X

Copyright 0 1993 Academic Press Limited A / / rights of reproduction in any / o m reserved

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8 Concluding remarks 285 Acknowledgements 286 References 287

1

Introduction

The electrophilic bromination of ethylenic compounds, a reaction familiar to all chemists, is part of the basic knowledge of organic chemistry and is therefore included in ever chemical textbook. It is still nowadays presented as a simple two-step, tra s-addition involving the famous bromonium ion as the key intermediate. T is mechanism was postulated as early as the 1930s by Bartlett and Tarbell (1936) from the kinetics of bromination of transstilbene in methanol and by Roberts and Kimball(l937) from stereochemical results on cis- and trans-2-butene bromination. According to their scheme (Scheme 1), bromo-derivatives useful as intermediates in organic synthesis

i

\ C=C / / \

+ Br,

slow

Br /+\

,C-C

/

\

\

+ Br-

fast

I

-C-Br I Br-C-

I

fast

+Nu-

I I NU-CI

-C-Br

Scheme 1

can be obtained with a high degree of diastereoselectivity from olefin and bromine, two readily available reagents. However, bromination is rarely interesting from a synthetic viewpoint (Okabe et al., 1982; Ueno et al., 1982; Rodriguez et al., 1984; Castaldi et al., 1986) since it is not as selective as Scheme 1 would suggest. This contrast between practical and conceptual approaches probably arises from the fact that detailed mechanistic studies are rather recent. Moreover, most of these studies are related to the first, ionization, steps whereas data on the last, product-forming, step are still scarce. Consequently, it remains difficult, or even impossible, to control the stereo-, regio- and chemo-selectivity of this addition. Despite much work (Sergeev et al., 1973; De la Mare, 1976; Schmid and Garratt, 1977), it has taken a long time to obtain reliable rate constants

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

209

readily interpretable in terms of mechanism. This is because bromination is both a very fast reaction, the kinetics of which are not easy to monitor in the absence of specially devized techniques, and a variable reaction, highly sensitive to the double bond substituents and to the medium (solvent, salts, etc.). It is only in the last two decades that large sets of data on kinetic substituent and solvent effects and on product selectivities, which can be related to the general background of physical organic chemistry,have become available. The objective of this chapter is not to repeat the reviews of others (Freeman, 1975;De la Mare and Bolton, 1982;Schmid, 1989;Ruasse, 1990)of the large body of relevant data, but to analyse the present status of the bromination mechanism (Scheme 2) and how it depends on the substituents and on the

Scbeme 2

solvent. Some features, the occurrence and structure of ionic intermediates, the involvement of bromine-olefin charge transfer complexes on the reaction pathway, for example, are now well established. For others, in particular return, there is no conclusive and extended evidence but only isolated data, the interest of which has to be examined in relation to the mechanism of analogous reactions, such as hydration and s N 1 nucleophilic substitutions. What is retained nowadays of the initial mechanism (Scheme 1) is the occurrence of a cationic intermediate. But bromine bridging is not general, and its magnitude depends mainly on the double bond substituents (Ruasse, 1990).For example, when these are strongly electron-donating, i.e. able to stabilize a positive charge better than bromine, P-bromocarbocations are the bromination intermediates. The flexibility of transition state and intermediate stabilization puts bromination between hydration via carbocations and sulfenylation via onium ions. As the understanding of the ionic intermediates has progressed, advantage has been taken of the fact that bromination, like sN1 heterolysis, is a carbocation-forming reaction. Kinetic data on this addition have therefore been used to examine in detail how the basic concepts of physical organic chemistry work as regards transition-state shifts with reactivity (Ruasse et al., 1984). Bromination lends itself particularly well to the quantitative application of the BEMA HAPOTHLE (acronym for Bell, Marcus, Hammond, Polanyi, Thornton and Leffler; Jencks, 1985). In particular, it has been possible to evaluate the transition-state dependence on the solvent and substituents. The major disadvantage that bromination shares with many

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other reactions is that its ionic intermediate is so reactive that thermodynamic data on its stability in solution are not available. However, if this difficulty can be overcome, the intrinsic kinetic contribution to the energy barrier of some brominations can be distinguished from the thermodynamic one. The role of the solvent in bromination has also been extensively studied (Ruasse and Motallebi, 1991). It is obvious that solvation is the essential driving force of this addition since it is extremely difficult to form a bromonium ion from bromine and ethylene in the gas phase whereas it is a very fast reaction in solution. The main contribution comes from assistance to bromide ion d e p r e in the transition state either by a second bromine molecule, leading to the very stable tribromide anion in halogenated or non-protic solvents, or by solvation, when protic solvents are involved. The magnitude of the kinetic solvent effects is thus directly proportional to the charge developed on the leaving bromide at the transition state; such solvent effects therefore provide a convenient measure of the progress of the reaction at the top of the kinetic barrier. In addition to electrophilic participation, solvents can also assist positive charge development nucleophilically, via a mechanism analogous to that postulated in S,2 (intermediate) solvolysis. This effect of nucleophilic solvents is not very important energetically, but it has some unexpected consequences on the stereo- and chemo-selectivity of bromination via carbocations. Significant recent modifications of the mechanism in Scheme 1 concern the demonstration that bromine-olefin charge transfer complexes (CTCs) are active intermediates on the reaction pathway and the possibility that ionic intermediates are formed reversibly. The existence of bromine-olefin CTCs was shown a long time ago (Dubois and Garnier, 1967b).The mechanistic consequences of this finding have been extensively discussed (Olah, 1975; Kochi, 1988), but not until 1985 was it proved that these CTCs are essential intermediates on the reaction pathway, as shown in Scheme 2 (Bellucci et al., 1985a). However, only a few equilibrium constants ( K )for their formation are available. It is still too early to be sure that these K-values are, or are not, significantly solvent- and/or substituentdependent. The same question still arises regarding return in bromination. Reversible formation of several bromonium ions has been shown to occur for various olefins under specific reaction conditions (Strating et al., 1969; Brown et al., 1984, 1990; Bellucci et al., 1987, 1990; Ruasse et al., 1991). Some characteristics of return emerge from these data, but the situation is still by no means clear. In what follows, we present first the experimental conditions under which it is possible to obtain data relevant to the study of the bromination mechanism, and the present evidence for the occurrence of charge transfer complexes and cationic intermediates on the reaction pathway. Once these

ELECTROPHILIC BROMINATION OF C=C

21 1

DOUBLE BONDS

preliminaries have been established, the following sections are devoted to kinetic substituent and solvent effects on this cation-forming halogenation; these effects are discussed in terms of kinetic selectivity, transition-state shifts and solvation. Finally, the problem of return, which raises questions about the nature of the rate-limiting step, is addressed from the few available results. To conclude, we shall take a brief look at the several points that still remain obscure: competition between free bromine and the so-called tribromide ion, the nature of the last, product-forming, step, etc.

2

P

Metho s for obtaining reliable bromination rate constants

The bromination of ethylenic compounds is in most cases a very fast reaction. Half-lives of typical olefins are given in Table 1. Most of them are very short. In order to obtain extended and meaningful kinetic data, it has been necessary to find suitable reaction conditions and to design specific kinetic techniques. This was not done until 1960-1970. As a consequence, kinetic approaches to the bromination mechanism are relatively recent as compared with those to solvolytic reactions, for example. Table 1 Bromination half-lives" of some ethylenic compounds at concentrationb and at 25°C. TCE'.~ trans-Cinnamic acid Ally1 chloride Stilbene 1-Pentene Styrene Cyclohexene trans-MeCH=CHEt Me,C=CHMe Me,C=CMe, EtOCH=CH,

-

8.3 hk.' 8.4 mino

-

10 s' 1.2 so

-

AcOH' 1 hf.8 1 1 hi 15 h" 1.2 minP 2 min"

-

660 msO 23 ms' 2.1 ms' 10 psu

M

reagent

MeOH"

12 hh 1.6 hj 1.5 min" 2.6 sp 860 msq 90 mss 63 ms' I10 psl I 0 ps* 4.5 psu

Calculated from bromination rate constants measured in the given references. [Br2] = [Ol]. - s-'; ~ second-order in bromine. From k in M - ' s - ' ; first-order in bromine. In 75% aqueous acetic acid. @DeYoung and Berliner (1977). Schmid et al. (1977b). 'Zhang (1981). 'Dubois and Bienvenue-Goetz (1968a). Ir In 1,2-dichloroethane, where the rate is about the same as in TCE. 'Bellucci et al. (1987). '"Yates and MacDonald (1973). " Bartlett and Tarbell (1936). "Modro et al. (1977). pGarnier and Dubois (1968). Ruasse and Dubois (1975). 'Bellucci et al. (1985b). 'Dubois and Fresnet (1973). 'Ruasse and Zhang (1984). " Ruasse (1985).

' 1,1,2,2-Tetrachloroethane.dFrom k in M

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212

KINETIC RATE EQUATIONS

Bromination can be a second-, third- or higher-order reaction, first-order in olefin but first-, second- or higher-order in bromine. Most of the early kinetic studies were focused on this complex situation (De la Mare, 1976). It is now M are necessary to obtain known that bromine concentrations less than simple or workable kinetic equations. This limit varies slightly with the solvent; for instance, in methanol lo-' M bromine leads to convenient rate ~ the highest equations (Rothbaum et al., 1948) but in acetic acid 1 0 - 3 is that can be used (Yates et al., 1973). In halogenated solvents, olefin bromination is second-order in bromine (1) (Modro et al., 1977; Bellucci et al., 1980). Moreover, even when small dCBrzl - k3[Ol][Br2]2 dt bromine concentrations are used, the bromination kinetics may be difficult to investigate if the solvent is not adequately purified. Adventitious traces of unknown catalytic species provoke very complex and irreproducible kinetic signals. Due to this complication, most of the old published data are unreliable. Nevertheless, good rate constants can be obtained when the solvents are pure (Schmid ec al., 1972; Bellucci et al., 1981). In particular, rate data in 1,2-dichloroethane, DCE (Bellucci et al., 1985b), and in 1,1,2,2tetrachloroethane, TCE (Modro et al., 1977), are now readily available. In protic solvents, bromination is first-order in bromine but the rate law (2) also includes terms related to the bromide concentration. In these media,

since solvent-incorporated products are formed, bromide ions are liberated during the course of the reaction. The electrophilic tribromide species is then produced according to the well known, fast equilibrium (3) (Bienvenue-Goetz Br,

+ Br- PK Br;

(3)

et al., 1980; Ruasse et al., 1986). Consequently, during a kinetic run, addition

of tribromide competes increasingly with that of free bromine, concentration [BrJf. This complication was resolved very early by adding bromide in excess with respect to analytical bromine ([Br2Ian= [Br2If + [Br;]) in order

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

213

to maintain the [Br21f/[ Br;] ratio constant throughout the reaction (Bartlett and Tarbell, 1936; Dubois and Bienvenue-Goetz, 1968a). The rate constants of free bromine and tribromide additions are obtained from the experimental constant, kobs, by using (4)to describe the kinetic effect of bromide ion. This

equation, first established by Bartlett and Tarbell ( 1936)and thereafter widely applied (Dubois and Huynh, 1968; Dubois and Garnier, 1967a; Rolston and Yates, 1969a), has been found to be applicable in a large variety of protic solvents (acetic acid, water, methanol, ethanol and their aqueous mixtures). The rate constant k is related unambiguously to the free bromine addition to alkene but the constant involved in the bromide-dependent term, denoted by kBrl, cannot be interpreted straightforwardly. Its mechanistic significance is complex because it can be associated with several pathways, namely, tribromide addition, salt effect on the free bromine reaction and/or bromideassisted bromine addition, these processes being kinetically indistinguishable (Dubois and Bienvenue-Goetz, 1968a). Empirical relationships ( 5 ) between the experimental rate constants and the k-values extrapolated to zero bromide concentrations have been log k

=a

log kobs + b

(5)

occasionally found (Dubois and Bienvenue-Goetz, 1968a) for limited sets of analogous alkenes. For example, relationships of this form have been obtained for the bromination in methanol of uncrowded alkenes (Dubois and Bienvenue-Goetz, 1968a), styrenes (Ruasse et al., 1978), stilbenes (Ruasse and Dubois, 1972) and 1,l-diphenylethylenes (Dubois et al., 1972a). The a-coefficientsare generally close to unity, but the b-values can vary significantly from one olefinic series to another. The possibility of using kobs instead of k in structure-reactivity correlations has also been discussed (Dubois and Huynh, 1968)in terms of k/kB,, ratios and K-values. It is, therefore, possible to avoid the tedious experimental work of measuring bromide ion effects systematically to obtain k. However the procedure must be applied carefully and critically to avoid erroneous extrapolations. It is noteworthy that in protic solvents most of the bromination rate constants used in mechanistic studies are k, the rate constant for free bromine addition only, that is, for a pathway from which any contribution of bromide is excluded since the involvement of this ion is taken into account in the kBrf term.

214

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KINETIC TECHNIQUES FOR BROMINATION

In halogenated and protic solvents, it is possible to obtain mechanistically significant rate constants by using bromine concentrations below M. But before 1960-1970 and even later, kinetic experiments were carried out using iodometric bromine titrations, which can be handled only for concentrations higher than this limit. In this latter range, the kinetic rate law generally exhibits several terms of higher order than second in bromine. Most work in the early period was devoted to understanding the complex rate equation. This historical, confused situation has been reviewed by De la Mare and Bolton (1982). Before modern kinetic techniques became available, reliable second order rate constants in methanol or in acetic acid were obtained for the reaction of weakly reactive olefins, such as stilbene (Bartlett and Tarbell, 1936), unsaturated carboxylic acids or ally1 chloride and acetate (Nozaki and Ogg, 1942).To enlarge the reactivity range, some workers used competitive kinetic techniques with large reagent concentrations (Bergmann et al., 1972). It was shown, when it later became possible to compare data obtained from direct and competitive techniques, that both lead to the same results only if the M. At higher concentrations, the reagent concentrations are below relative reactivities of two alkenes measured competitively are generally smaller than those obtained from direct kinetic experiments (Mouvier et al., 1973).The reactivity ratios are highly dependent on the alkene concentration. pair is For example, the rate ratio of the l-hexene/4,4-dimethyl-l-pentene about 5.8 when calculated from the directly measured rate constants, but only 1.8 if obtained in experiments where both alkenes are lo-' M in methanol at 25°C. Other significant data are shown in Fig. 1. As a consequence, rate constants obtained by competitive techniques cannot be considered as reliable. Bromination data became accessible over a large reactivity range when it became possible to follow low bromine concentrations. All the modern kinetic techniques are based on the fact that, since bromination is a second- or third-order reaction, bromination half-lives of a few milliseconds to several seconds can be obtained by working at very low reagent concentrations. For example, second-order rate constants as high as lo9 M - ' s - ' can be readily measured if the reagent concentrations are 1 0 - 9 ~ the , half-life of the bromine-olefin mixture then being 1s. Very low bromine concentrations are followed either spectrophotometrically or electrochemically. In halogenated solvents, only spectroscopic determinations are possible. The bromine extinction coefficient at its maximum (A,, = 400-450nm) is about 150-250~-'cm-', so that the workable ~ et al., 1985a). Taking into concentrations are not less than l O P 4 (Bellucci

ELECTROPHILIC BROMINATION OF C=C

01

1

ldLM

I

I

10.)~

215

DOUBLE BONDS

16%

,

-

[A]=[B]

Fig. 1 Concentration dependence of rate-constant ratios measured by competitive brominations (data from Grosjean et al., 1973).

account this limitation and the present performance of stopped-flow equipment, the highest bromination rate constants available in halogenated ~ range. solvents are in the lo5 M - s-’ In protic solvents it is possible to obtain kinetic data for more reactive alkenes by following tribromide rather than free bromine, although the reaction half-lives are shorter than those in halogenated media (see Table 1). Since the presence of bromide ions in large concentrations (0.05-0.5 M ) is necessary to obtain mechanistically significant rate constants, tribromide is generally the major bromine species in these media in which its formation constant is high (16, 92, 177 and 400 in water, acetic acid, methanol and ethanol respectively) (Bienvenue-Goetz et al., 1980). The tribromide extinction coefficients (20 000-40000 M - cm- ’) at the absorption maximum (280-300nm) are much greater than those of free bromine (Dubois and Herzog, 1963); it is therefore possible to follow analytical bromine concenM. Under these conditions, bromination rate constants trations as low as of about lo5- lo6 M - s- are accessible by spectroscopic techniques (Dubois and Garnier, 1967b). Other methods use the electrochemical properties of the bromine-tribromide couple. In these techniques, very small bromine concentrations are first produced by quantitative electrolysis of a bromide added to the reaction medium (Poupard et al., 1983). After adding the alkene, the bromine uptake is followed either potentiometrically or amperometrically. In the “concentrostat” technique (Dubois et al., 1965, 1973a), the bromine concentration

’

’ ’

M.-F. RUASSE

216

Potentiometry

:

Concentrostat

8

,

8

,

I

,

I

'

I

'

I

' I

I

Spect rophotornet r y

II I I I I

I I

2

Arnperometry

I I I

Fig. 2 Scope of kinetic methods for bromination.

is maintained constant during the kinetic run by automatically compensating its consumption by the olefin. With this method, rate constants up to 5 x lo5 M - s~ - l have been obtained in methanol. In potentiometry, the variation of the potential of a Pt electrode relative to a calomel reference electrode represents the time-dependent bromine concentration. Available [BrJ is about 2 x 10-5-10-4 M; pseudo-first-order ~ conditions ([Ol] >> [BrJ) have to be used. Rate constants up to lo4 M - s-l can thus be obtained (Atkinson and Bell, 1963; Dubois et al., 1968). Finally, the most advanced method is couloamperometry. Halogen concentrations in the 1 0 - 8 - 1 0 - 9 ~range are determined by a specially devised amperometric set-up. Second-order conditions ([BrJ w 2 x [Ol]) are used so that rate constants as high as lo9 M - s~ - l can be measured (Dubois et al., 1964, 1983). With these techniques (Fig. 2), bromination rate constants in acetic acid, water, methanol, ethanol and more generally in any solvent in which a bromide is soluble to at least 0.2 M are obtained with a precision of about f2% when the method is easily applied and f5% when it is used close to its limit.

3

Bromine-olefin charge transfer complexes as essential intermediates in bromination

In agreement with Dewar's proposal (Dewar and Leplay, 1961) and by analogy with the long-established halogen-aromatic molecular complexes

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

217

(Andrews and Keefer, 1951, 1964), donor-acceptor complexes between halogens and ethylenic compounds have been postulated for a long time. The first experimental evidence for their existence was obtained spectrophotometrically in 1967 (Dubois and Garnier, 1967b); transient charge transfer bands appear in the spectra when acceptor halogens interact with donor alkenes in freons, low-polarity solvents in which bromine addition is slow. The complexes absorb in the 240-320nm range. In agreement with theory (Mulliken, 1952), a linear relationship (6) between the energy of

bromine CTCs, hvCTC,and the ionization potential I D of the alkenes is found for 14 ethylenic compounds substituted by linear alkyl groups (Me, Et, n-Pr, n-Bu). Moreover, the interaction energies are linearly related to the activation energies. At about the same time, a Russian team (Sergeev et al., 1973) published analogous data, including some equilibrium constants for the formation of these alkene-bromine complexes. After these preliminary observations, the problem was to establish whether these CTCs are essential intermediates in olefin bromination (Scheme 3). Are \

/

/

\

C=C

+Br,

1

-+

Br /+\ ,C-C /

Br-

9’

Scheme 3

they formed in a route competitive with that leading to the cationic intermediate? Or do they occur in an equilibrium step prior to bromonium ion formation? In other words do the n-complexes dissociate heterolytically to a-complexes? Several arguments based on the parallelism between substituent effects on the kinetics and on charge transfer energies tend to favor the second hypothesis (Dubois and Garnier, 1968). Gebelein and Frederick (1972)also attempted to obtain some evidence for CTC involvement in bromination from the concentration dependence of the rate constant, but they failed since it was impossible to obtain the CTC equilibrium constants with the spectroscopic techniques available at that time: Subsequently, and although no experimental proof was accessible, it was commonly agreed that CTCs are active intermediates in bromination. In particular, Olah et al. ( 1974a) concluded from nmr spectra that the bromine-

218

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adamantylideneadamantane adduct (Strating et al., 1969) in non-nucleophilic media is not a bromonium ion but a molecular n-complex. Taking advantage of this observation, Olah (Olah and Hockswender, 1974), continuing his work on electrophilic aromatic substitution, developed the controversial idea (Ruasse and Dubois, 1975) that the rate-lim‘ ing transition state of olefin bromination resembles either a n- or a Q-co plex when the solvent is non-polar or highly polar, respectively. Some years later, Kochi et al. (Fukuzumi and Kochi, 1981) applied their theory on electron and charge transfers to electrophilic alkene bromination (Kochi, 1988) by comparing the reactivities of various alkenes in bromination and in mercuration. Although the substituent effect trends in the two reactions are totally different, a linear relationship (7) is observed when the reactivities

“h,

[log(k/ko) - hVCTIBr, = [log(k/kO) - hVCTIHgXz

(7)

are corrected by work terms evaluated from the corresponding energies, hv,,, of their charge transfer complexes. This result fits very well Kochi’s postulate, which is illustrated by a thermochemical cycle (Scheme 4) in which the

D

+A

K

% [D+,A-]*

[D,A]

CD A-I, +9

AGc= Ahv,,

+ AGs

Scheme 4

activation free energy changes are expressed as the sum of two terms, one, AGs, related to solvation, and the other the charge transfer energy of the donor-acceptor (DA) complex which includes steric effects. Unfortunately, this approach suffers from the fact that relationship (7) is based only on alkenes with one to four linear alkyl groups, i.e. alkenes whose bromination does not exhibit any significant kinetic sensitivity to steric effects. It would be interesting, therefore, to know if (7) is also valid for compounds bearing one or more branched substituents. Moreover, the work terms evaluated from the CT energies take into account the electronic reorganization but not that of the nuclei, a microscopic event which is probably energetically important. In this respect, it is noticeable that the distance between the C-C bond and bromine decreases significantly on going from the bromine-olefin n-complex ( d = 3.0A) to the bromonium ion ( d ’ = 1.9A) (Prisette et al., 1978). Although the involvement of molecular bromine-olefin complexes as active intermediates in bromination had been widely assumed, this was demonstrated

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

219

a

only recently (Bellucci et al., 1985a). In contrast with the earlier CTC observation, which dealt with olefins of very reduced reactivity (as a result of eithe the solvent or the substituents), Bellucci's team investigated the brominati n of cyclohexene in 1,2-dichloroethane. By using high alkene M ) concentrations and by monitoring (lo-'- lo-' M ) and low bromine the cyclohexene-bromine CTC at 287 nm near its absorption maximum, but far from that of bromine, they were able to evaluate the spectroscopic = 5520 250 M - ' cm- at 287 nm) and the formation characteristics constant (K, = 0.47 f 0.08 M-') of this complex at 25°C. The thermodynamic parameters of CTC formation and of the third order bromination of this alkene were also measured (Scheme 5 ) . It was shown that the negative

A H + = -8.37kcalrnol-' AS+ = -64.0e.u.

A H = -4.60kcalmol~' AS = - 17.0e.u. Scheme 5

temperature coefficient, frequently observed for bromination in non-protic solvents, is consistent only with a bromination mechanism where the CTC is an essential intermediate (route 2-3, Scheme 3). These authors have applied their method to measure the formation constant of the CTCs arising from adamantylideneadamantane (Bellucci et al., 1989) and tetraisobutylethylene in several solvents (Brown et al., 1990).The results, together with previous less reliable data, are shown in Table 2. Since it is now established that CTCs are involved in the bromination pathway, a question about the meaning of the experimental bromination rate constant arises. These constants are not those of an elementary step but are the products of the CTC formation constants KCTC and of the rate constants ki for CTC ionization into the 0-intermediates (8).

Information on the mechanism is mainly obtained from kinetic solvent and substituent effects, i.e. from p- and m-values, as discussed below. These coefficients are therefore a composite of p- and m-values for CTC and ionization steps as shown in (9). Obviously, neither pCTCnor mCTCis available P = PCTC+ Pi m = mCTC mi

+

(9)

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Table 2 Formation constants of bromine-alkene charge-transfer complexes. Alkene

KCTCIM -

Crotonic acid" 1 -Hexeneb 4-Me- 1-penteneb Cyclohexeneb Cyclohexene' Ad=Add TIBE' TIBE" TIBE"

0.08

0.145

0.33

0.36 0.47 289 9.71 1.72 2.5

'

Solvent DCEJ Hexane Hexane Hexane DCEJ DCEJ DCEJ AcOH MeOH

Buckles and Yuk (1953). * Sergeev et al. (1973). 'Bellucci et al. (1985a). Bellucci et al. (1989). eTetraisobutylethylene; Brown et al. (1990). 1,2-Dichloroethane.

'

at present. However, it can be assumed that they are negligible with respect to pi and mi. Substituent and solvent effects are all the more important when the charge modification on going from reactants to products or to transition states is large. Despite their name, there is no charge separation in the CTCs, whereas the rate-limiting second step is an ionization process. Values of pCTC and mCTC should therefore be small compared with pi and mi respectively. Recent data on tetraisobutylethylene bromination (Table 2) support this hypothesis. On going from acetic acid to methanol, the rate constant increases by a factor of 10 whereas the CTC formation constant is hardly modified (Brown et al., 1990). Moreover, when the ring substituent effects on the bromination rates of a-methylstyrenes (Ruasse et al., 1978) are compared with those on equilibrium constants for the formation of the iodine-acetophenone CTCs (Laurence et al., 1979), it is calculated (Ruasse, 1990) that the contribution of the olefin-bromine CTC formation to the p-values obtained from kinetic data cannot be greater than 9%. Accordingly, experimental p- and m-values are generally discussed in terms of effects related to the ionization step of bromination only. 4

The ionic intermediates: bridged bromonium ions or open B- bromocarbocations

Although there is general agreement about the occurrence of ionic intermediates on the bromination pathway, there are only few direct observations of these bromocations. It is still difficult to decide whether they are bridged or open depending on the double-bond substituents.

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

221

EXPERIMENTAL OBSERVATIONS

'H and 13C nmr spectra of methyl-substituted bromonium ions in nonnucleophilic superacid media have been obtained by Olah's group (Olah et al., 1968, 1974b; Olah and White, 1969). The dependence of the chemical shifts of the three-membered ring carbon atoms on the number of methyl groups is discussed in terms of either symmetrically bridged or unsymmetrical bromonium ions in equilibrium with a pair of open B-bromocarbocations (Olah, 1975). For the parent ion, the data are in agreement with a static bridged structure. gem-Dimethyl groups produce a dissymmetry in the bridged structure and a small contribution from equilibrium (10). Additional Br

\

7c-c\

+/

=

Br /+\ +CT

7

/Br c-c/ \ \+

substitution by a third methyl on the other carbon would significantly favour

( 10). For the symmetrically substituted ethylene bromonium ions, the results

suggest that their structure is also a mixture of a bridged species and a rapidly equilibrating pair of open ions. However, this proposal was not confirmed by later work, the I3C nmr spectra of these deuteriated ions being temperature-independent (Servis and Domenick, 1987). Moreover, recent MNDO calculations show that there is no kinetic barrier between these two structures (Galland et al., 1990). Consequently, an equilibrium such as (10) cannot describe the bromocations. One conclusion from these results is that most of the charge of these ions is on the ring carbon atoms and not on the bromine. In contrast, '3C nmr spectra of ring-substituted B-bromocumyl cations [2] can be unambiguously interpreted in terms of open B-bromocarbocations, since the ring substituent effects on the chemical shifts are similar to those on the corresponding non-brominated cations [l], even for the electron-attracting p-trifluoromethyl group (Olah et al., 1972).

Bromonium ion stabilities in the gas phase have also been measured in ion cyclotron resonance experiments by Beauchamp's group (Staley et al., 1977). The heterolytic bond dissociation energies shown in Table 3 are taken as a

222

M:F.

RUASSE

Table 3 Relative stabilities" (in kcal mol-') of substituted bromonium ions and alkyl carbocations in the gas phase.b R+

D (R+-Br-)

R'

D (R+-Br-)

0

+ 52.5

- 5.6

-4.5

- 18.8

Y

- 18.4

-

16.5

- 30.2

A

-41.4

With respect to the parent ethylenebromonium ion and expressed as heterolytic bond dissociation energies D (R+-Br-). 'Data from Staley ef a[.'(1977). 'Calculations (Galland ef al., 1990) indicate that this ion is not bridged but open.

R\

CH-CH

/

Br

P' \

Br

'

+ R-CH-CH-R'

'dr

measure of these relative stabilities. As expected, stability increases with methyl substitution. An interesting conclusion is obtained by comparing the data for the t-butyl [ 31 and the 2-bromomethyl-2-propyl [4] cations. Since, according to theoretical calculations, the second cation is probably open, a bromo-substituent should stabilize an aliphatic carbocation by about 2kcalmol-' in the absence of bridging. It is also observed that the

\>/

CH

I CH,

c37

CH,

\>/

CH

I,

CH, 1147

CH,Br

ELECTROPHILIC BROMINATION OF C=C

223

DOUBLE BONDS

three-membered ring ion is more stable than the corresponding 1-bromoethyl cation by about 1.4 kcalmol-'. These thermodynamic data are useful for checking theoretical calculations. They have also been used to estimate the solvation enthalpies of these ions by combining gas phase data and their heats of ionization in superacid media (Larsen and Metzner, 1972). The solvent significantly attenuates the effect of methyl substituents on the gas phase stability. Data on molecular structure of bromonium ions are sometimes extrapolated from that of the tribromide-adamantylideneadamantane bromonium ion pair [6] (Slebocka-Tilk et al., 1985), the only stable ionic bromination intermediate that can be isolated and whose crystal structure has been determined. Since the first observation by Strating et al. (1969), it has been established that bromine addition to adamantylideneadamantane [ 51 in

c51

C6l

non-protic solvents stops after bromonium ion formation because of complete steric inhibition of trapping by nucleophiles. Some of the most relevant geometric data on this ion are shown in Scheme 6a. An important feature of

Br

Br

the cation is that it is not symmetrical, there being a difference of 0.078 A between the two C-Br bond lengths. However, this asymmetry probably arises from constraints in the crystal packing produce& by the tribromide counter-ion and is not necessarily conserved in solution. Despite the exceptional character of this bromonium ion, these structural data are valuable for calculations.

M.-F. RUASSE

224

THEORETICAL CALCULATIONS

Early interest of theoretical chemists in bromonium ions was focused on two aspects: are they bridged or open and do they resemble n- or a-complexes? Old semi-empirical (Bach and Henneike, 1970) and recent ab initio (Hamilton and Schaefer, 1990, 1991) calculations are in complete agreement with experimental data as regards the structure of the parent ethylenebromonium ion. Its most stable structure is definitely symmetrically bridged. Early ab initio results showed that the bridged form [7] is more stable than the 2-bromoethylcation [S] and the 1-bromoethylcation [9] by 1-4 and Br /+\

,c-c

H / H

c71

H ‘\ H

+ H ,C-CH

181

Br ,Br

I

’

C+ CH, H ‘ c91

15-30 kcalmol-’ respectively (Poirier et al., 1981, 1983; Scheme 6b). These calculations indicate also a high energy barrier on going from [7] to [9] but an almost insignificant barrier between [7] and [8]. Species [S] cannot be a stable structure, since it corresponds to a very flat segment along the open/cyclic structure. interconversion potential and not to a secondary minimum (Fig. 3; pp. 226-7). These results have been recently confirmed by more elaborate ab initio methods including electron correlation and polarizability functions. Structure [7] (Scheme 6c) is found to be more stable than [9] by only 1.5 kcalmol-’. Structure [ 81 does not exist as a minimum on the potential energy surface and spontaneously collapses to [ 71. It is reasonably expected that substituents significantly modify the structure of the parent ethylenebromonium ion. However, little attention has been paid by theoretical chemists to this assumption, since it is difficult to tackle it by ab initio methods. Recently, MNDO calculations on methyl-substituted bromonium ions have been attempted (Galland et al., 1990). The similarity of the MNDO and ab initio results for the unsubstituted ion (Scheme 6d) gives some confidence in the semi-empirical method. The minimum energy profiles for the opening of the variously substituted ions are shown in Fig. 3. Increasing the number of substituents leads to a flattening of this profile, i.e. to a decrease in the energy difference between open and bridged forms. In every case the curve has only one minimum; therefore there is no equilibrium, as described by (lo), between the two limiting structures. For unsymmetrically substituted ions, the open form is slightly more stable, whereas for symmetrical ions the bridged structure is favoured.

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

225

Finally, every kind of calculation shows that there is no substantial charge on the bromine atom of bromonium ions (Cioslowski et al., 1990), in agreement with the conclusions from nmr spectra. This result is relevant to the possible reversibility of bromonium ion formation, as discussed later. Despite much discussion, there is no simple answer to the question of whether bromonium ions may be viewed as n- or o-complexes. This arises because there is no clear-cut experimental criterion for distinguishing the two types of bonding. Calculated and experimental bond lengths and angles (Scheme 6 ) have values intermediate between those expected for one or other kind of complex. Depending on the data set considered, bromonium ions have been classified as n- or a-complexes. The X-ray structure for adamantylideneadamantane bromonium ion seems to agree better with a a-complex, whereas from ab initio calculations the ethylenebromonium ion would seem to exhibit n-character. As concluded by Slebocka-Tilk et al. (1985), it is possible that “such a distinction is semantic and has no real chemical meaning.” In the early stages of bromination studies, the charge transfer complex and the subsequent bromonium ion were called bromine-alkene n- and o-complexes respectively. Although this nomenclature is not rigorous from an orbitalbonding point of view, there is at present no way of improving it.

KINETIC DATA AND BROMINE BRIDGING IN TRANSITION STATES AND INTERMEDIATES

Kinetic data can be discussed in terms of bromine bridging in ionic intermediates if the transition states of the ionization step are late. It appears that this is the case in the bromination of a wide variety of olefins, and in particular of alkenes, stilbenes and styrenes. Large p - and m-values for kinetic substituent and solvent effects (p. 253) consistent with high degrees of charge development at the transition states, are found for the reaction of these compounds. It can therefore be concluded that their transition states closely resemble the ionic intermediates. The relative magnitude of the kinetic effects of two substituents, R, and R,, on the C, and C, carbon atoms of the double bond (Scheme 7) is taken as a measure of the symmetry of the charge development and therefore of bromine bridging in the bromocations. It is assumed that in a bromonium ion the effects of R, and R, must be similar, whereas for a P-bromocarbocation, C: ,the effect of R, must be significantly greater than that of R,. Consequently, the substituent effects are analysed in terms of a multipathway scheme (Scheme 7) where open carbocations and the bridged ion are formed via discrete pathways with rate constants k,, k , and kgr respectively (Ruasse and Dubois, 1974). The rate constant k in (4) is therefore the sum of these three

M . - F . RUASSE

226

4

Br +0,19 2.01

H

Me--

H

,c ’ 1.49

1 H

c.

1.10 1.511 “Me

H

I

I

I

I00

50

0

*

4 Br +0.08

I

50

68“4

100

0

Fig. 3 Minimum energy profiles for the opening of bromonium ions (Galland et al., 1990). They are not double-well curves, i.e. bridged and open structures are not in equilibrium, whatever the number of methyl substituents.

constants corresponding to different structure-reactivity relationships. The magnitude of bridging in the intermediates is readily obtained from the k,/kB, ratios (Scheme 7 ) . Depending on the nature and the number of substituents, the multipathway mechanism is applied in various ways. k = k,

+ kp + kgr

(11)

For alkene bromination, present kinetic data show that their trmsition states are always bridged, whatever the number of alkyl groups on the double

ELECTROPHILIC BROMINATION OF C=C

Br

227

DOUBLE BONDS

+0,08

1. 8 8 v l \ \ 2 . \ 55

'

\

-c\98" 1 . 4 8C . H -3.11 1.48\ H

!.I1

-

'H

Me

4

n

.""

\

0 5 1,1

C-

H--]l.ll

H

1S O

\\+

C-

1.50\''Me

Me

I05''

0

t

Me

Me

Fig. 3 Continued.

bond. First of all, values consistently close to unity have been measured (p. 268) for the rn-coefficients of their Winstein-Grunwald relationships in protic solvents; for instance, using the Winstein-Grunwald Y-parameters, in is 1.16, 1.10, 1.31 and 1.40 for 1-pentene (Garnier and Dubois, 1968), trans-2-pentene, 2-t-butyl-3-methyl- 1-butene (Ruasse and Zhang, 1984) and methylideneadamantane (Ruasse and Motallebi, 1988), respectively. It is therefore commonly agreed that the transition states for bromination of alkenes are always highly charged and closely resemble the ionic intermediates. Early evidence for a symmetrical charge distribution is found in kinetic data which show that the effects of linear alkyl groups are additive, whatever their number and their relative positions (Dubois and Mouvier, 1968). This preliminary result was challenged by Bergmann et al. (1972) who analysed

M:F.

228

IBV/

R1\

Br,

+

R1\

H

/Ca=F

/

H

-

Br pathway

/Ca-C<

/"./

RUASSE

R,

R1\+

Br /

/c.--r,-

\

C a pathway

R2

+/

C , pathway

R1ya-C
Scheme 7

kinetic effects of linear and branched alkyl groups in terms of a twocarbocation scheme using a multiparameter equation involving nine terms. Owing to the unreliability of the competitive kinetic technique used and to the complexity of the statistical treatment, the conclusion of this work cannot be considered mechanistically significant. A more conclusive result was obtained by Bienvenue-Goetz and Dubois (1978), who measured the kinetic effect of several very varied electron-attracting non-conjugated groups R on methylethylenes [lo], [111, [ 121 and [ 131. The effect of R is expected to be either

2 c 101


2

Me

1121

Me9 Me

1131

the same or different in the series [lo]-[13], depending on whether the transition states are bridged or open. For example, if the charge distribution is carbocation-like, the bromination rate should be highly R-dependent for [111 but weakly so for [131. The results given in Fig. 4 show definitely that the bromination transition states of these alkenes are bromonium ion-like whatever the number and the position of the substituents. This conclusion is not in complete agreement with theoretical calculations (p. 224), which imply that the ionic intermediate derived from isobutene closely resembles an open fl-bromocarbocation, whereas those from cis- or trans-Zbutenes would be bromonium ions. This difference between experiment and calculations is not fully understood, but could be attributed to some

ELECTROPHILIC BROMINATION OF C=C

3: 0

DOUBLE BONDS

229

I

4

2

0

Fig. 4 Symmetrical charge distribution in bromonium-ion like transition states in alkene bromination (data from Bienvenue-Goftz and Dubois, 1978). The effect of the R-substituent depends neither on the number nor on the position of methyl groups on the double bond.

charge reorganization induced by solvation on going from transition state to intermediate. For aryl-substituted ethylenes, where the aryl group can be conjugated with the developing positive charge, the transition states are either carbocationlike, or bromonium-like or a mixture of these two limiting forms, depending on the electron-donating abilities of the ring substituents. This has been shown for substituted stilbene and styrene bromination, the transition states of which are late according to their m-values (1.20 and 0.96 respectively; Ruasse and Dubois, 1975). For these olefins, it has been shown that two or three pathways of Scheme 7 can compete, i.e. (11) must be considered in its totality. This implies that the structure-reactivity relationships describing the substituent effects are curved. Upward curvature has been observed in the po plots for stilbene, styrene and u-methylstilbene bromination in methanol (Ruasse and Dubois, 1972; Ruasse et al., 1978; Ruasse and Argile, 1983). In no case can these curvatures be interpreted coherently by Yukawa-Tsuno equations in terms of variable contributions of polar and resonance effects. Application of the multipathway scheme (Ruasse, 1990) leads to the results summarized in Table 4. For stilbenebromination, a markedly non-linear structure-reactivity relationship is observed (Fig. 5 ) . Detailed analysis of the kinetic effects of two substituents, X and Y, on each aromatic ring shows that the three pathways leading to the C: and C i carbocations and to the bromonium ion can

Table 4 Contribution of bridged and open forms of the ionic intermediates in the bromination of some aromatic olefins in methanol, as calculated by the multipathway scheme"

logkb

YOC,

% C,

% Br

100 100 80 60 40 15 100 100 100 100 100 100 100 80 60 15

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 20 40 60 85 0 0 0 0 0 0 0 20 40 85

Ref.

X-C,H4-C=CHRZ

Styrenes

I

X

R,

R2

4-OMe 4-Me H 3-CF3 4-NO2 3,5-(CF,)z 4-OMe 4-Me H 3-CF3 3,5-(CF,), 4-OMe 4-Me H 3-CF3 3,5-(CF,)z

H H H H H H Me Me Me Me Me H H H H H

H H H H H H H H H H H Me Me Me Me Me

Rl

6.53 4.28 3.18 1.08 0.08 0.60 7.82 6.34 5.09 2.96 1.08 6.48 4.54 3.51 1.50

--

0.22

d

d d d d d d d d d

d d

d d

d d

trans-Stilbenes I

X

Y

4-OMe 4-OMe 4-Me 4-Me H 3-c1 3-CF3 3-CF3 3-CF3 4-NO2 4-OMe H H 4-CF3 3-CF3 H

H 3-CI H 4-NOz H H H 3-CF3 4-NO2 H H 4-OMe H H 4-OMe 4-CI

R H H H H H H H H H H Me Me Me Me Me Me

R 4.32 3.92 1.86 0.40 1.04 0.12 0.08 - 1.30 - 1.53 -0.71 5.95 3.61 2.63 -0.03 2.56 2.20

e

+c

+ + + +

e

+ t

+ + t

0 63 0 0

100 37 100 100 0 100

100

0

e

+ + + + + + 0 0 0 0 0 0

e e

f

f f

f f 9 9

9 g g 9

"Ruasse (1990). b k in M - s~C 1 for free bromine addition at 25 "C. 'This pathway occurs but its magnitude cannot be calculated exactly. References: dRuasse et al. (1978); 'Ruasse and Dubois (1973); Ruasse and Dubois (1974); Ruasse and Argile (1983).

'

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

231

Fig. 5 Reactivity-structure relationship for the bromination of monosubstituted stilbenes (data from Ruasse and Dubois, 1972).The curvature shows the X-dependence of the competition between carbocation and bromonium ion pathways.

compete. For a single electron-donating substituent, 4-methoxy for example, only the CJ path is followed, whereas with two electron donors (X = 4-OH, Y = 4-OMe) both carbocations coexist. One electron-donor group associated with an electron attractor favours the open cation and two electron attractors the bridged intermediate. Owing to the fact that the three pathways must be taken into account in the analysis of the complete kinetic data set, it is not possible to obtain strictly quantitative results but only qualitative characteristics of the competition between the three paths. This has made it impossible to establish rate-product correlations like those found in styrene and a-methylstilbene bromination. For styrene brornination, the curvature in the pa plot is not obvious (Fig. 6). Before it was accepted that the structure-reactivity relationship was not strictly linear, several significantly different p-values were reported (Dubois and Schwarcz, 1964; Rolston and Yates, 1969a; Pincock and Yates, 1970; Yates et al., 1973), depending on the substituent range studied. This p-variation was understood when the effects of the ring substituents on the bromination rates of styrenes, a-methylstyrenes and trans-p-methylstyrenes were measured (Ruasse et al., 1978). The X-dependence of a- and p-methyl effects in bromination was compared with the same effect in hydration (Chang and Tidwell, 1978). Figure 7 shows a very different trend for these two electrophilic additions. The difference is consistent with a carbocationic intermediate for all the hydrations, but, for styrene bromination, with a bromonium ion increasingly competing with the bromocarbocation as X becomes more and more electron-attracting. The outcome of this competition was calculated for substituents varying from strong electron donors (4-OH) to electron attractors [3,5-( CF,),]. The results were checked by measuring the X-dependence of the stereochemistry of bromine addition (p. 239).

M

232

-F. RUASSE

Fig. 6 Reactivity-structure relationship for the bromination of ring-substituted styrenes (data from Ruasse et al., 1978). Competition between bromonium and carbocation intermediates.

Ole-

0,

brornination

1.5

,

&.OM.

- 0.5

&!Me

3-Me

4.Cl

3.CI

,

3.CF3

3.5-(CF,I2

Fig. 7 Comparison of the X-dependence of the a-methyl effect in bromination and hydration of X-substituted styrenes (data from Ruasse et al., 1978).

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

233

Effects of substituents on both rings of a-methylstilbene can be analysed in terms of competition between the two carbocations only (Fig. 8; Ruasse and Argile, 1983). Even in the presence of an electron-attracting substituent, no contribution of a bromonium ion is detected. The replacement of a hydrogen atom on the ethylenic carbon by a methyl group stabilizes the carbocations enough to preclude bromine participation. A similar situation is found on going from styrenes to a-methylstyrenes, the bromination of which involves exclusively a carbocationic intermediate whatever the ring substituent (Ruasse et al., 1978). For X-substituted a-methylstilbenes, the linear pa relationship shows that only the tertiary bromocarbocation is involved. But for the Y-monosubstituted a-methylstilbenes, there is a sharp breakdown in the pa plot, which is readily interpreted as indicating a change in the mechanism from the secondary to the tertiary pathway when Y changes from electron-attracting to electron-donating (Fig. 8). The kinetic data can be quantitatively analysed in terms of competition between the secondary and tertiary carbocations; the results are confirmed by the regiochemistry of methanol attack on these intermediates (p. 242). I n summary, bromination intermediates are bromonium ions as long as there is no conjugated substituent able to stabilize the developing charge better than the bromine atom alone. When a strongly electron-donating substituent is conjugated with this charge, the open b-bromocarbocation is favoured. The two-fold nature of the ionic intermediate can therefore be viewed as a result of the entering bromine atom and the substituents competing to stabilize the positive charge. This picture is supported by the

t

o x + 0.83ao;

Fig. 8 Reactivity-structure relationship for the bromination of (a) X- and ( b ) Y-monosubstituted cr-methylstilbenes (data from Ruasse and Argile, 1983).Intermediates are tertiary bromocarbocations, except when Y is strongly electron-donating; in this latter case, they are secondary bromocarbocations.

234

M:F.

RUASSE

bromination of some unsaturated substrates where the anchimeric participation of hydroxy or phenyl groups overwhelms bromine bridging. For example, the reaction of some unsaturated alcohols goes through five- or six-membered cyclic oxonium ions (12), rather than through bromonium ions (Williams et al., 1969; Bienvenue-Goetz et al., 1970). Phenonium ion is also suggested as the intermediate in 4-allylanisole bromination (Dubois et al., 1973b). CH,=CH(CH,),OH

+ Br,

--+

BrCH2$J,

Br-

--+

Products

(12)

H’ It is still not clear whether steric constraints can modify the magnitude of bromine bridging. There is at least one example that suggests that this is possible. Non-additive kinetic substituent effects and cis-dibromoadducts imply that the intermediate of cis-cyclooctene bromination in methanol is a b-bromocarbocation (Dubois and Fresnet, 1974). It must also be noticed that most of the previously described results were obtained in methanol. The question is therefore whether they can be transposed to other solvents. Kinetic solvent effects described below are generally large and almost independent of olefin structure. These data suggest that solvent assists bromide ion departure strongly but positive charge development in the cationic part of the transition state only weakly. As a consequence, the charge distribution, i.e. the relative contribution of the bromonium and carbocation intermediates, cannot vary significantly with the solvent. This proposal is supported by the generally small solvent dependence of bromination stereochemistry. PRODUCT DATA AND BROMINE BRIDGING FROM STEREO- AND REGIO-CHEMISTRY

Since bromine addition to olefins leads to brominated compounds of synthetic interest, there are many studies of bromination products in the literature. Typical examples have been reviewed by Schmid and Garratt (1977). However, there are few systematic product analysis studies related to the role of the structure and the solvent in determining bromination selectivities. Bromination can exhibit stereo-, regio- and chemo-selectivity when the reaction is carried out in the presence of nucleophiles (solvent or added salt). When the ionic intermediate is a bromonium ion, a stereospecific but non-regioselective reaction is expected. In contrast, for an open bromocarbocation, the products should be formed regioselectively but not stereospecifically. These considerations were understood very early since, in fact, Roberts and Kimball ( 1937) suggested bridged ions as bromination inter-

ELECTROPHILIC BROMINATION OF C=C

235

DOUBLE BONDS

mediates because of the trans-bromine addition to cis- and trans-2-butenes. Twenty years later, by studying the chlorination of cis- and trans-di-tbutylethylenes, Fahey (1966) showed that halogen bridging is a general rule. It is expected that, owing to steric repulsions between the two branched groups, the cis-alkene would prefer to react via an open P-chlorocarbocation 1141 where free rotation can occur rather than via a chloronium ion [ 151.

c 141

c 151

However, the product in carbon tetrachloride is exclusively the antidichloroadduct, demonstrating unambiguously that chlorine bridging is essential in this disfavoured reaction. Since bromine is a better bridging group than chlorine, a fortiori bromination intermediates must be bridged whatever the steric constraints in the alkene. The generality of this finding is confirmed when bromination products of less congested alkenes are systematically studied in methanol containing 0.2 M NaBr (Ruasse and Chrktien, 1993; Table 5). Whatever the substituents, the bromination of 1,Zdisubstituted alkenes is stereospecific: the cis-alkene leads to the threodibromide and threo-solvent-incorporated product only; the adducts from the trans are systematically erythro. As concerns the regioselectivity of methoxybromide formation, it is generally claimed that Markovnikoff addition takes place. However, as shown in Table 5, this rule is only roughly followed. Monosubstituted alkenes give preferentially the Markovnikoff adduct when the substituents are not bulky; when they are branched, anti-Markovnikoff addition is preferred or is even exclusive. Cis- and trans-alkenes lead also to significant amounts of antiMarkovnikoff products. The regioselectivity seems to be determined by a subtle balance between steric and polar factors, which cannot be expressed quantitatively. In contrast, the reaction of gem-disubstituted alkenes is completely regioselective, in agreement with Markovnikoff’s rule, even when the substituents are highly branched, such as t-butyl or adamantylidene. This result agrees with MNDO calculations, which show that the ion derived from gem-dimethylethylene bromination has an open structure, but not with the kinetic results (Fig. 4). As stated before, this difference is not readily understood. Because of their complexity, the chemoselectivity data of Table 5 have not been fully interpreted either.

236

M:F.

RUASSE

Table 5 Stereo-, regio- and chemo-selectivity of alkene bromination in methanol (0.2M NaBr) at 25°C."

R,\

7

3

-

/c=c\R4

R2

,-

DB

/

/R3

R1,

C(OMe)-CqBr R f R4 P

MB,

3

CBr-CTOMe

MB,

R4

~

Me n-Pr i-Pr neo-Pe Me Me n-Pr n-Pr i-Pr i-Pr t-Bu t-Bu i-Pr i-Pr Me i-Pr t-Bu' Me

~~

H H H H H H H H H H H H H H Me Me Me Me

H H H H H Me H Me H Me H Me H i-Pr H H H Me

H H H H Me H Me H Me H Me H i-Pr H H H H H

"Ruasse and Chretien (1993). b T = threo; E

=

49.4 37.3 18.8 47.7 21.9E 21.2T 0 10.2T 0 0 84.7 73.9 65.6 81.4

63.0Eb 59.4Tb

18.8E 31.OT

11.3 12.1 20.7 9.3 35.OE 28.8T 54.9E 38.6T 56.8E 34.71 0 0 0 0

39.3 50.7 60.5 43.0 37.OE 40.7T 43.1E 50.OT 45.1E 5 1.2T 43.1E 65.2T 81.2E 69.OT 15.3 26.0 21.0 18.6

erythro. ' 13.4% bromoalkene.

For the methyl-substituted ethylenes, i.e. in the absence of any steric effects, there is a roughly linear relationship between the chemoselectivity and the I3Cnmr chemical shift of the most substituted carbon atom of the bromonium ions (Dubois and Chrttien, 1978). This selectivity is therefore discussed in terms of the magnitude of the charge on the carbon atom and the relative hardness of the competing nucleophiles, according to Pearson's theory (Ho, 1977). However, this interpretation does not take into account the substituent dependence of the nucleophilic solvent assistance, which must play a role in determining this chemoselectivity.

ELECTROPHILIC BROMINATION OF C=C

237

DOUBLE BONDS

The solvent has no influence on the stereoselectivity of bromine addition to alkenes (Rolston and Yates, 1969b), but it could have some effect on the regioselectivity, since this latter depends not only on polar but also on steric effects. Obviously, it modified the chemoselectivity. For example, in acetic acid Rolston and Yates find that 2-butenes give 98% dibromides and 2% solvent-incorporated products whereas, in methanol with 0.2 M NaBr, dibromide is only about 40% and methoxybromide 60%. There are no extensive data, however, on the solvent effects on the regio- and chemoselectivity which would allow reliable predictions. More results are available on the bromination products of aromatic olejns and in particular on styrenes and stilbenes. Bromination of X-substituted styrenes (13) in acetic acid (Rolston and Yates, 1969b) and in methanol

'\\

+ Br,

RoH

XwHOR-CH,Br

+

"Q-

CHBr-CH,Br

(13)

(Ruasse et al., 1978) is totally regioselective and shows X-dependent chemoselectivity. This is partly in agreement with the kinetic data, which indicate no primary carbocation but rather a competition between the benzylic carbocation and the bromonium ion, depending on X. According to the data of Table 6, bridged intermediates would lead to more dibromide than open ions do. From these results and from those on gem-, cis- or trans-disubstituted alkenes, empirical rules have been inferred for chemoselectivity: (i) more solvent-incorporated product is formed from open than from bridged ions; (ii) methanol competes with bromide ions more efficiently than acetic acid. Table 6 Chemoselectivity ( % solvent-incorporated products) in bromination of styrenes, XC6H,CH = CH,. X 4-OMe H 4-Br 3-CI 3-NO, 4-NOZ

AcOH, 0.1 M LiBr"

MeOH, 0.2 M NaBrb

__

98

16.0

6.5

3.6

"Rolston and Yates (1969b). bRuasse ef al., (1978).

85 75

-

15

238

M:F.

RUASSE

The stereoselectivity of bromination of cis- and trans-B-methylstyrenes, where the kinetic data show competition between benzylic carbocations and bromonium ions, has been widely studied. As early as 1968, Fahey and Schneider observed that cis- and trans-anetholes, 4-MeOC6H,CH= CHMe, are brominated in carbon tetrachloride with the same lack of stereoselectivity but that the parent B-methylstyrenes exhibit some selectivity. At about the same time, Rolston and Yates (1969b,c) obtained similar results in acetic acid, where the formation of 80% dibromide is observed. Finally, the dependence of the dibromide stereochemistry on the ring substituent in P-methylstyrene bromination in dichloromethane is found to agree quantitatively with the magnitude of bridging calculated from the kinetics in methanol (Ruasse et al., 1978). In contrast, in this latter solvent, the major ( > goo/,) methoxybromides are formed completely regioselectively and stereospecifically anti, whereas the minor dibromide is formed with some stereoselectivity only (Scheme 8). The same regio- and stereo-selectivity is observed x~H(OMe)CHBrMe

xm

100% erythro

CHBr-CHBr Me

erythro/threo = 63/37 (X = 4-OMe) 100/0 [X = 3,5(CF,),]

Scheme 8

for the formation of acetoxybromides from unsubstituted 8-methylstyrene in acetic acid. It seems possible to generalize for these aromatic olefins that: (i) dibromides are formed with stereoselectivity that depends on the substituents and the solvent (Tables 7 and 8); (ii) the reaction of the cis-isomer is less stereoselective than that of the trans; (iii) the mixed adducts are formed completely regioselectively and stereospecifically whatever the solvent and the substituents. Less extensive data on the selectivities of product formation from cis- and trans-stilbene bromination are available; the stereoselectivity of the corresponding dibromides is solvent- and concentration-dependent (Table 9; Buckles et al., 1962; Heublein, 1966; Bellucci et al., 1990). Solvent-dependent lifetimes and ion-pairing of these intermediates can be responsible for the observed variations in the stereo- and chemo-selectivity. Assuming that bromonium ions and carbocations are formed in discrete pathways, the influence of these factors can be readily understood. On the one hand, bridged ions react stereospecifically whatever the medium; the

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

239

Table 7 Stereochemistry of dibromides in the bromination of p-methylstyrenes in methylenechloride: rate-stereoselectivity relationship." X trans-4-OMe trans-H cis-H trans-3-CF3 trans-3,5-(CF3),

YOErythro

% kB;

63 81 28 91 100

0 77

-

93 98

"Ruasse et al. (1978). Bromonium ion pathway calculated from kinetic data.

Table 8 Solvent-dependence of the stereochemistry of dibromides from cis- and trans-p-methylstyrene bromination. YOanti-addition from

Solvent C6H12b

CC1,b AcOH' Cl,CH-CHC12C CI,CH,' (AcO),O' C6H5N02' MeNOZb MeCNb

Ea

cis

trans

1.9 2.2 6.2 8.2 9.1 21 34.8 35.9 37.5

85 78 73 66 72 49 45 46 69

92 90 83 90 90 83 82 81 89

"Dielectric constant. bPannel and Mayr (1982). 'Rolston and Yates (1969b).

Table 9 Solvent-dependence of the stereochemistry of dibromides from cis- and trans-stilbene bromination." % anti-addition from

Solvent

cs2

CCI, C1,CCN CI,CCO,Me C6H5N02

"Heublein (1966).

cis

trans

81 77 34 51 29.5

94.5 89 82.5 79 83.5

240

M:F.

RUASSE

solvent can only modify the chemoselectivity by changing the ion-pair dissociation. On the other hand, the stereochemistry of bromide attack on the carbocations should depend on their lifetimes. In non-nucleophilic non-polar solvents such as hexane or dichloromethane, the cation is not stabilized by the medium; it is therefore short-lived enough not to undergo significant equilibration before reacting with the counter-bromide ion. As a result the highest stereoselectivities for cis-olefin brominations are found in non-polar media. In contrast, in polar solvents such as nitrobenzene, equilibrium ( 14) can be achieved before the intermediate is trapped.

Ph RA

H

€ € A P H h

(14)

Bromination is less stereoselective, and the reactions of cis- and trans-olefins tend to be stereoconvergent. The stereospecific formation of the mixed bromoadducts in protic media, such as methanol or acetic acid, could be interpreted in the light of the recent finding (Ruasse et al., 1991) that these solvents assist the formation of the ionic intermediate nucleophilically. If a solvent molecule is close to the cationic part of the transition state in the rate-limiting step, the intermediate can be trapped by this solvent molecule in a necessarily trans mode with respect to the first bromine, before the two components of the ion-pair diffuse away from each other (15). This would

s\

0

HY

‘c=’

-

I I

-C-Br

I

,Br-

-+

so-cI

X-Br

+ Br- + H +

(15)

I

inhibit any competition between solvent and bromide ions in the trapping of the intermediate and any conformer equilibrium, which would lead to non-stereoselectiveadducts. Moreover, chemoselectivityshould also be highly dependent on this solvent assistance, which would favour the solventincorporated products over the dibromides. There is at present not enough data on the magnitude of this solvent effect to understand fully its influence on the stereo- and chemo-selectivity of bromination in general. C,HC,H,Y, The bromination products of a-methylstilbenes, XC,H,C,Me= have been extensively studied in methanol as a function of X and Y (Ruasse and Argile, 1983). In agreement with kinetic data, which establish that the intermediates are exclusively tertiary and/or secondary bromocarbocations, the bromination of these olefins is completely regio-selective but hardly stereoselective at all. The two diastereoisomeric di-bromides and methoxy-

/

:,B

biE

E:

0

. Y I

242

M:F.

RUASSE

bromides are formed in the same erythrolthreo ratio (70/30), whatever X and Y, in both dichloromethane and methanol. When the CT carbocation is predicted to be the only intermediate, methanol attacks the C, carbon atom exclusively; when Y is electron-donating, the kinetics predict that the carbocation will be secondary, and this is confirmed by the finding that the sole product in methanol is the corresponding methoxy-bromide. For strongly electron-releasing Y (4-OH, 4-OMe), 1,2-dimethoxy-1,2-diarylpropanes resulting from a fast solvolytic displacement of the tertiary bromine are obtained according to Scheme 9. When secondary and tertiary pathways compete, the reaction in methanol leads to a mixture of the two regioisomeric methoxybromides in a ratio that agrees with that calculated from the kinetics (Table 10). Finally, the bromination of these olefins in methanol is also completely chemoselective,only solvent-incorporated products being obtained, even in the presence of 0.5 M NaBr. To summarize, when the kinetic data predict that only bromonium ions or only bromocarbocations are formed, the bromination products are obtained stereospecifically and regiospecifically, respectively, whatever the solvent. Olefin brominations involving open intermediates lead to more solvent-incorporated products in methanol or acetic acid than those involving bridged ions. This chemoselectivity can be interpreted in terms of the hard and soft acid and base theory (Dubois and Chrktien, 1978). Methanol assistance to intermediate formation also plays a role in determining product-selectivity (Ruasse et al., 1991). When the kinetics indicate that there is competition between bridged and open cations, neither the solvent-dependent stereoselectivity, nor the Table 10 Regiochemistry of the exclusive and non-stereoselective methoxybromide formation in the methanolic bromination of trans-a-methylstilbenes, XC,H,C( Me)=CHC,H,Y: rate-regioselectivity relationship." ~

~~~

X

Y

4-OMe H 4-CF3 H H 4-c1 3-CF3 4-CF3

H H H 4-c1 4-OMe 4-OMe 4-OMe 4-OH

% AdT

Yo AdS

% M

% kTb

% kTC

65*

0 0 0 0 0 20'

0 0 0 0 40 60 0 0

100 100 100 100 37 0 0 0

100 100 100 100

100 100 100 35 0 0 0

100 100

35 0 0 0

Ruasse and Argile (1983); see Scheme 9 for definition of AdT, Ads, M and k,. *From kinetics. From regiochemistry. Elimination products from the tertiary pathway. Elimination products from the secondary pathway. a

ELECTROPHILIC BROMINATION OF C=C

243

DOUBLE BONDS

regio- or chemo-selectivity is readily understood. Several factors (ionpairing, lifetimes of intermediates, conformational equilibration, nucleophilic assistance, etc.), whose effects cannot be investigated separately, probably influence them. More systematic work in this area, related to the selectivity of carbocation reactions, would be useful.

5

Kinetic substituent effects

POLAR EFFECTS OF ALKYL GROUPS

In the nineteen sixties, there was some confusion about the value of p*, the reaction constant for polar effects of alkyl groups on bromination rates, as a*. For 22 alkenes calculated according to Taft’s equation, log (k/ko) = p* 1 substituted by one, two or three linear alkyl groups, there is a satisfactory relation (16) between their reactivities, log k, in methanol and the sum of their log( k/ko) = - 3.22 C a* polar constants (Mouvier and Dubois, 1968). The correlation in which the rates vary over 6 log. units includes tetramethylethylene, the most reactive alkene. The additivity of substituent effects, demonstrated by ( 16), was the first kinetic evidence for a symmetrical charge distribution in the rate-limiting transition states of alkene bromination. As expected, deviations from (16) are found for alkenes bearing one or several branched groups. In order to take into account the steric effects, the E,. authors applied the extended Taft relationship, log(k/k,) = p * C a* 6 1 The resulting correlation is (17) where p*, now -5.4, is considerably more

+

log (k/ko)

=

-

5.43C a*

+ 0.96 C E ,

negative than the value in (16). Faced with this contradiction, Dubois and Bienvenue ( 1968b) chose a series of ethylenic compounds bearing single non-conjugated linear heteropolar groups whose a*-parameters cover a range wider than those of alkyl groups and whose steric parameters ( E , ) hardly vary (Table 11). The resulting p*-value in (18) is -3.1, in agreement with that found in (16). This result was later confirmed by including in the correlation ( 18) additional alkenes bearing the same heteropolar groups

M.-F. RUASSE

244

Table 11 Determination of the effects of alkyl groups on the rates of bromination of CH2= CH-CH,X in methanol" at 25°C. log k b

X n-Pr CH,OH CH,Ph CH,OEt CH,OPh CH,OCOMe CH,CI CH,CN

-0.115 0.32 +0.215 +0.495 +0.8 1 0.69 + 1.05 + 1.13

+

- 0.36

+

-0.24

-

-0.38 -0.19 -0.33

"Dubois and Bienvenue-Goetz (1968b).bk in 'See Shorter (1982).

2.59 1.82 1.72 1.30 0.48 - 0.07 -0.78 - 1.50 M - s~ - l .

associated with one or two methyl groups ( Bienvenue-Goetz and Dubois, 1978). It was shown (Dubois and Bienvenue-Goetz, 1968b) that (17) and the very negative p*-value come from an artefact due to the occurrence of a relationship between o* and E , for linear alkyl groups ( E , = 2.520*). The p*-value of - 3.1 from ( 16) and (18) can therefore be considered as reliable and as a generally valid expression of the polar effect in bromination. Hyperconjugation does not seem to have much effect on alkene reactivity towards bromine, since (16) applies whatever the number of alkyl groups on the double bond. However, only cis-olefins are involved in this correlation. To include geminally substituted olefins, an additional term is necessary, as in (19) where d is unity for the gem-disubstituted compounds and zero for log k = - 3.03

1 + 0.43d + 6.89 O*

(19)

the others. This term can be associated with hyperconjugative effects (Bienvenue-Goetz and Dubois, 1978). Because of the absence of any obvious reference value, the p*-value of -3.1 is not readily discussed in terms of charge magnitude or brominebridging at the rate-limiting transition states. For alkene hydration, it is now accepted that the intermediates are carbocations (20). The corresponding structure-reactivity relationship (21) is obtained by using o,' and 0,'

log

k H + = - 12.3[0;

+ 0.60(02 + 0.080 - 0.084)] - 10.1

(21)

ELECTROPHILIC BROMINATION OF C-C

DOUBLE BONDS

245

substituent constants for R, and R,, respectively (Knittel and Tidwell, 1977), and not og-constants. In (21), the D-term related to hyperconjugation represents double bond stabilization by R, . There are more similarities between bromination and arylsulfenyl chloride addition leading to a thiiranium ion (Scheme 10).The p*-values of - 1.00 to - 1.8 for sulfenylation (Ruasse et al., 1979; Schmid et al., 1977a; Collin et al., 1969) are significantly Ar

I

Scheme 10

less negative than that for bromination, suggesting, in agreement with CNDO calculations (Bach and Henneike, 1970), that the carbon atoms of thiiranium ions are less charged than those of bromonium ions. Surprisingly, the absolute value of p* for bromination in methanol is significantly greater than that for solvent-assisted solvolysis of unbranched secondary alkyl derivatives in 20% aqueous ethanol (p* = -1.17; Bentley et al., 1981). It is difficult, however, to compare these two cation-forming reactions, since the solvent assistance to charge development in the ionization processes is very different (p. 273). The p*-value for bromination established in methanol is also valid in a variety of other protic solvents. Linear correlations between the bromination rates of unbranched alkenes in methanol and those in a 7&30 methanol-water mixture (M70) [(22); Barbier and Dubois, 19681, in pure water C(23); Bienvenue-Goetz and Dubois, 19681 and in acetic acid [(24); Ruasse and Zhang, 1984) are observed. An approximately linear relationship (25) between log

kM70

+

= 0.90 log ~ M ~ O H2.6

(22)

the rates in methanol and those in tetrachloroethane (TCE), where the kinetics are respectively first- and second-order in bromine, is also found (Modro et al., 1977). This almost insignificant solvent sensitivity of p* in bromination is surprising in view of the solvent dependence of p* in solvolysis (Bentley et al., 1981), where the reaction constant changes from -2.1 to -4.28 and to -9.1 on going from acetic acid to water and hexafluoroisopropyl alcohol,

246

M.-F. RUASSE

respectively. This different behaviour is not fully understood (p. 273) but suggests that bromination data in non-nucleophilic fluorinated alcohols would be useful. The kinetic effect of trans-S-alkyl or heteropolar groups R on bromination of styrenes, PhCH=CHR, has also been investigated and compared with the same R-effects on ethylene (Bienvenue-Goetz and Dubois, 1975). A fairly linear relationship (26) between the two sets of data is observed. The

attenuation of the polar R-effect can be attributed to differences in charge distribution at the rate-limiting transition states. Those for styrenes are carbocation-like [ 161 whereas in the alkene series they are bromonium ion-like [17]. It has been argued (Schmid et al., 1977a) that the p*o* correlations on the same olefins challenge this interpretation.

STERIC EFFECTS OF ALKYL GROUPS

Steric effects of alkyl groups are more difficult to describe quantitatively, since, in any electrophilic addition, up to four substituents on a double bond can interact with the entering electrophile and with each other. After the failure of the extended Taft analysis of bromination data for mono- to tri-substituted alkenes (p. 243), Grosjean et al. (1976) chose a series of tetraalkylethylenes, Me,C=CMeR,, some R, being branched substituents, and found an acceptable relationship (27) using Taft’s steric parameters only. A more general correlation (28), including additional tetrasubstituted ethylenes

1

log ( k / k o ) = 1.29 E: with linear groups only, was obtained when Hancock’s E: parameters (Hancock et al., 1961) were used. It is difficult to understand why the steric effects are additive, when they are generally non-additive (Shorter, 1972,1982;

ELECTROPHILIC BROMINATION OF C=C

247

DOUBLE BONDS

Gallo, 1983), and how the polar effects disappear totally; this result is probably fortuitous and again due to the relationship between (r* and E,. It must therefore be concluded that parameter scales are inadequate to describe the kinetic influence of alkyl groups in bromination and in electrophilic additions in general. Qualitatively speaking, it is clear that retarding steric effects very easily outweigh the accelerating polar effects. For example, the highest bromination rate is found for tetramethylethylene, since replacing one methyl by an ethyl slows the reaction slightly. Ultimately, the accumulation of steric effects leads to totally unreactive alkenes, such as tetraneopentylethylene (Andersen et al., 1985) and tetraisopropylethylene (Langler and Tidwell, 1975). Moreover, it appears from the data of Table 12 that the retarding effect of a branched group depends on the other double bond substituents; the more crowded the ethylenic bond, the higher the steric retardation caused by a t-butyl group for example. It has been claimed (Grosjean et al., 1976) that interactions between the entering bromine and substituents control the bromination rates; in addition, Table 12 shows that substituent-substituent interactions also play a role in determining the reactivity. These latter interactions between non-bonded groups could lock the branched alkyl groups in conformations which would depend on the rest of the alkene. However MM calculations show (Ruasse et al., 1990) that the favoured conformations of R are the same in tetraalkyl- and adamantyl-ethylenes. It is possible, however, that conformational changes occur on the charged transition states, which are more congested than the ground states. Data on the conformations of R in the corresponding bromonium ions would be useful in this respect. Whatever the case, topological treatments, such as DARC-PELCO analysis (Dubois et al., 1981b) or the branching equation of Charton (Charton and Charton, 1973) may be more suitable for describing large sets of bromination data. Table 12 Alkene reactivity" towards bromine: dependence of steric retardation by R o n the double-bond crowding.

H Me Et i-Pr t-Bu neo-Pe

0.67 2.60 2.69 2.51 1.98 1.78

4.57 6.11 6.13 5.66 5.22

5.02

6.11 7.15 7.13 6.27 6.23 4.61

5.62 6.20 6.08 4.92 3.20 3.96

"log k in MeOH at 25°C with k in M - ' s - ~ for bromine addition. bDubois and Mouvier (1968). 'Grosjean et a/. (1976). dRuasse et al. (1990).

248

M:F.

RUASSE

The high sensitivity of bromination to steric effects has also been discussed in terms of open or bridged rate-limiting activated complexes (Schmid and Tidwell, 1978). Since transition states for hydration and sulfenylation are unambiguously open and bridged respectively, it was suggested that the structure of bromination transition states can be determined by comparing the kinetic effects of alkyl groups on the three electrophilic additions. Unfortunately, the corresponding log/log correlations are so poor that they are inconclusive. This disappointing result is not surprising in view of the balance between polar, steric and hyperconjugative effects, which is noticeably different for the three reactions (Ruasse et al., 1979). Sulfenylation is much less sensitive to polar effects than bromination (p&, = -3.10 and pXrscl = - 1.0). Hyperconjugation is important in hydration but not in bromination (p. 245). Finally, the steric requirements of the hydronium ion, bromine and arylsulphenyl chloride differ widely. In particular, the steric contribution of two t-butyl groups depends on their relative positions and also on the entering electrophile (Scheme 11;R = t - Bu). As a consequence,

HAHBr R

cis

R

HAR Br R

trans

H

gem

Scheme 11

the k,is/k,,ons-ratios, which have sometimes been used to estimate the magnitude of steric effects (Chang and Tidwell, 1978), cannot be interpreted independently of the electrophile. In addition to the fact that steric crowding can slow the reaction by hindering bromine approach to the double bond, it appears now that bulky substituents can modify the bromination mechanism by inhibiting nucleophilic solvent assistance to ionization of the CTC and/or nucleophilic trapping of the ionic intermediates. Assistance to the rate-limiting ionization step by

ELECTROPHILIC BROMINATION OF C=C

2

3

L

5

DOUBLE BONDS

249

logk,MeOH8

Fig. 9 Comparison of polar and steric effects of alkyl groups on bromination rates branched (0) and adamantyl (A) alkenes in acetic acid and in methanol of linear (a), (Ruasse and Zhang, 1984; Ruasse et al., 1990). Polar effects are identical in both solvents [full line, eq. (24)], but steric effects differ. Deviations of branched alkenes are attributed to steric inhibition of nucleophilic solvation by methanol.

nucleophilic solvents was first suggested by systematic deviations of crowded alkenes from the correlation between the rates of bromination of linear olefins in methanol and in the less nucleophilic acetic acid (Fig. 9; Ruasse and Zhang, 1984). Since the bromination of highly congested unsaturated compounds cannot be assisted by the solvent, due to inhibition of solvent approach to the double bond, their rates are smaller than those for the assisted reaction of unencumbered ethylenic substrates. The more crowded the double bond, the less important the solvent participation is (p. 272). Consequently, part of the retardation induced by branched alkyl groups results from inhibition of solvent assistance. In particular, the large steric effect observed in adamantylidenealkanes (Fig. 9; Ruasse et al., 1990) can be interpreted in these terms. The rate of the product-forming step is generally considered to be very fast, since it is an anion-cation reaction. However, bulky substituents can also slow this last step by making nucleophilic attack on the bromonium ion difficult. The most famous example of steric inhibition of.product formation is the bromination (29) of adamantylideneadamantane in carbon tetrachloride (Strating et al., 1969). Bromine adds to this alkene, i.e. the electrophile can Br;

M.-F. RUASSE

250

AGh AG C / \

C’ / \

A k - i << k,

Br, Br-,

k Products B

kN < k - i

L L RC RC Fig. 10 Free energy profiles of bromination: (A) when bromonium ion formation is irreversible and ( B ) when it is reversible.

approach the congested double bond, but the reaction stops at the bromonium ion, bromide attack on this ion being totally inhibited. It therefore appears that steric effects must be discussed not only in terms of bromonium ion formation but also of bromonium ion trapping. When the last, productforming, step is significantly slower than the first step, the bromonium ion can be formed reversibly, as shown in Fig. 10. This has been found recently in the bromination of highly congested alkenes such as tetraisobutylethylene (TIBE [ 181; Brown et al., 1990) and adamantylidenealkanes (Ad=CRR’ [ 191; Ruasse et al., 1991).

TIBE

[I81

Ad=CRR

c 191

There are only a few studies of the bromination products of congested alkenes. Such products generally consist of the corresponding allylic bromoderivatives, which are consistent with /%proton elimination by the counter-ion from the bromonium ion. For example, the ionic bromination of octamethylcyclopentene in CC14 leads exclusively to 1,2-di(bromomethyl)hexamethylcyclopentene as in Scheme 12 (Mayr et al., 1986). Bromine addition (30) to

ELECTROPHILIC BROMINATION OF C=C

251

DOUBLE BONDS

Br -HBr

d

/

- G-G Br -

J

CH,Br

-HBr

Scheme 12

1,2-dimethyldi-t-butylethylenein CC1, affords the 3,4-di(bromomethyl)2,2,5,5-tetramethylhexene-3,in agreement with a mechanism similar to that of Scheme 12 (Lenoir, 1978). It is also noteworthy that isopropylideneadamantane is chlorinated by t-butyl hypochlorite (31) in the allylic position (Meijer et al., 1982).

To sum up, the rate retardation attributed to steric effects of bulky alkyl groups can arise from substituent-electrophile, substituent-substituent and substituent-solvent interactions in the first ionization step of the reaction and also from substituent-nucleophile interactions in the product-forming step. It is therefore not surprising that the usual structure-reactivity correlations or even simpler log/log relationships cannot satisfactorily describe the kinetic effects of alkyl groups in the electrophilic bromination of alkenes. ,

M:F.

252

RUASSE

KINETIC EFFECTS OF ARYL SUBSTITUENTS

Early values of p + for the ring-substituent effect in the -4.5 range were obtained for styrene bromination in methanol (Dubois and Schwarcz, 1964) and in acetic acid (Rolston and Yates, 1969a). The magnitude of p + , closely similar to that for t-cumyl chloride methanolysis, -4.82, was one of the first pieces of evidence for open P-bromocarbocations as intermediates in this electrophilic addition. It is noteworthy that the same value was obtained with different substituents, in methanol with electron-donors and in acetic acid with electron-acceptors. This was not considered inconsistent, since at that time the reaction constant of the a+-defining reaction was not known to exhibit significant solvent dependence (Stock and Brown, 1963).However, the absolute magnitude of p + for styrene bromination in acetic acid became higher and higher (-4.21, Rolston and Yates, 1969a; -4.71, Pincock and Yates, 1970; -4.83, Yates et al., 1973) as the substituent set was extended toward the more negative a+-constants; in methanol an upward curvature characteristic of a mechanistic change was found for the complete p+a+relationship including strong electron donors (4-OH) and acceptors [ 33(CF,),] (Ruasse et al., 1978). The quantitative analysis of structure-reactivity relationships and the measurements of significant p-values for ring substituent effects on arylolefins must take into account several related problems: (i) the change of the intermediates from open carbocations to bridged bromonium ions as the aromatic ring is less able to stabilize the positive charge on the benzylic carbon atom; (ii) a variable balance between polar and resonance effects which can be expressed by Yukawa-Tsuno (32) or Young-Jencks (33) equations (Yukawa et al., 1966; Young and Jencks, 1979) and which results log(k/ko) = pn(an+ R Ao') log(k/ko) = pnan+ p r ACT+

(32) (33)

partly from ring rotation out of the plane of the double bond or of the vacant orbital of the developing carbocation, and partly from resonance saturation; (iii) a solvent effect on p, which would arise from transition-state shifts as the stability of the intermediate changes; and, finally, (iv) a dependence of p on the other substituents attached to the double bond, which can be handled in terms of interaction coefficients.

ELECTROPHILIC BROMINATION OF C=C

253

DOUBLE BONDS

The question of bridged and/or open intermediates has been considered in Section 4, where the data on kinetic substituent effects were discussed with the help of the multipathway scheme (Scheme 7) to determine the relative importance of bromonium and carbocation paths. It is not straightforward to obtain significant p-values for each of them from the complex pa relationship (34) and (35) corresponding to this scheme for an a,fl-R,,R,

(34)

disubstituted olefin. The general procedure involves, first, the search for limiting situations, where it can be reasonably assumed that only one pathway contributes, in drder to estimate the reaction constant range, and, secondly, an iterative adjustment that selects the p-values of (35) most closely corresponding to the experimental data. Values collected in Table 13 have been obtained by this analysis for styrenes ( ArCH=CH,) and stilbenes (ArCH=CHAr'). For these latter series it has been assumed that the balance Table 13 Values of p and m ' for ring-substituent and solvent effects in the bromination of aromatic olefins trans-Ar-C( R)=CHR' in methanol at 25°C. R

R'

logkx=H

pnb

H Me H OMe

H H Me H

3.18 5.14 3.51 9.32

-4.80' -4.26' -4.72 - 1.58

H Me

Ph Ph

0.63 2.65

Ph

H

4.62

P'

PS

Styrenes -4.8 -2.8 -4.7 0.0 Stilbenes -1.6 -5.52 -5.4 -1.7 -4.0 -4.87 1,l-Diphenylethylenes -2.9 -3.579

pB

mW-G

Ref.

-1.8

0.96' 1.01f

h

-

-1.7

-

-1.0

-

0.45

-

1.20' 1.03f

-

1.04f

h h

i

i

k I

p-values calculated from the multipathway mechanism; mw_,-values calculated using the Y-parameters of the Winstein-Grunwald scale. bpn and p' for polar and resonance effects respectively, calculated using the Young-Jencks equation, when p" = p', p" = p ' . 'In AcOH, p" = -5.7 (Bodrikov et al., 1973). dRuasseand Dubois (1975). 'In AcOH, p" = -5.76. 'Ruasse and Lefebvre (1984). % AcOH, p" = -4.45. References: *Ruasse et al. (1978); 'Ruasse and Dubois (1984); JRuasse and Dubois (1974); 'Ruasse and Argile (1983); 'Dubois et al. (1972a).

2 54

M.-F. RUASSE

between polar and resonance effects does not differ from that in the reaction defining o+,i.e. there is no need to use a Young-Jencks equation. For styrene bromination in methanol, application of the dual parameter equation (33) does not statistically improve the initial p+a+ correlation (Ruasse et al., 1978); for stilbenes, (33) gives - 1.9 and - 5.9 for p" and pr respectively, two senseless values from a mechanistic point of view since resonance effects would be anomalously high as compared with analogous reactions (Ruasse and Dubois, 1972). In contrast, polar and resonance effects must be separated in order to analyze the data for a-substituted arylolefins [ArC(R)=CHR with R # HI . Their bromination involves open carbocation intermediates only. Resonance effects cannot be fully developed at the transition states, since the aromatic ring is not in the same plane as that of the developing carbocation, because of steric constraints. Accordingly, application of (33) gives p' < p". Attenuation of resonance arises mainly from stereochemical factors, at least in the monosubstituted 1,l-diphenylethylene [201 and a-methylstilbene [21] series; the p'/p" ratios can be related to the dihedral angle between the substituted phenyl ring and the plane of the ethylenic bond.

While p* for the polar effects of alkyl groups does not vary with the solvent, p" for the polar effects of aromatic substituents is solvent-dependent. For example, there is a fairly linear log/log relationship between the bromination rates of styrenes in acetic acid and methanol (36) with a slope higher than unity, to be compared with 0.99 in (24). The p+-value for styrenes

in acetic acid is therefore -5.7. This agrees fairly well with that measured for the reaction of the same olefins in the same solvent but with N bromosuccinimide instead of free bromine (Bodrikov et al., 1973). Similar results have also been obtained for a-methylstyrenes and 1,l-diphenylethylenes, their p-values being significantly more negative in acetic acid than in methanol (Ruasse and Lefebvre, 1984). This solvent-sensitivity of p" and p' can be attributed to the fact that nucleophilic solvent assistance is

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

255

substituent-dependent and that it increases as the charge delocalizing ability of the phenyl ring decreases. However, it can also arise from transition-state shifts due to variable solvent stabilization of the carbocationic intermediates, as discussed below. Finally, as shown in Table 13, p for an aromatic ring is also strongly dependent on the other substituents at the double bond; it varies from - 1.6 to - 5.5 on going from a-methoxystyrenes to stilbenes. This variation, which is related to the well-known non-additivity of multiple substituent effects, and contrasts with what is observed for alkene bromination, is discussed in the next paragraph, devoted to substituent interaction and selectivity relationships in bromination. The p"- and p'-values for electrophilic bromine additions to arylolefins are in the same range as those for other reactions via analogous benzylic carbocations. However, generally the comparisons are only qualitative because of significant differences in the experimental conditions and in the mechanisms. For example, as has already been mentioned, the reaction constant of t-cumyl chloride methanolysis is -4.82 (Okamoto et al., 1958), i.e. slightly higher than that for a-methylstyrene bromination in methanol, where the intermediate resembles that in the solvolysis of cumyl derivatives (Scheme 13).

p+=p"=pr=-4.82

p"= -4.26; p'= -2.11

Scheme 13

The three-pathway bromination of stilbenes can interestingly be compared with the dehydration of 1,2-diarylethanols (Noyce et al., 1968), which unambiguously takes place through two CI- and p-aryl carbocations. The ratios of the two reaction constants, p , ' / p g , are very similar (Table 14), despite large differences in solvents and in the nature of the encounter complexes formed in the step preceeding the ionization. Numerous p-values for various electrophilic additions to styrene itself are available (Schmid and Garratt, 1977). Strictly speaking, the reaction constants measure only the sensitivity of the reaction to substituent effects; they depend at the same time on the solvent, on the position of the transition state on the reaction coordinate (charge magnitude) and on the way in which substituent effects are transmitted (charge location). In particular, the observed trend of p-values for the chlorination (-3.22; Yates and Leung, 1980), bromination (- 5.7; Ruasse et al., 1978) and sulfenylation (- 2.41 ;

256

M:F.

RUASSE

Table 14 Values of p for carbocation-forming dehydration" and brominationb of 1-aryl-2-phenylethane derivatives.

P,'

Dehydration

Bromination

R

H

Br

P,' PS

- 3.11 - 1.00 3.8

- 5.52 - 1.6 3.5

I Ps

Noyce et al. (1968). bRuasseand Dubois (1972).

Kharasch and Orr, 1956) of styrenes in acetic acid results from a combination of the last two factors. Bromination and chlorination go through transition states in which the benzylic carbon atom is charged; the differences between their p-values probably reflect differences in the magnitude of this charge. Sulfenylation, on the other hand, goes through a thiiranium ion, and the attenuation of p is partly due to the greater distance between the charge and the ring substituents; in fact, p for sulfenylation should be compared with pBr for bromination via bromonium ions. For these reasons, p-values for different electrophilic additions must be compared with caution, and, most frequently, the results of these comparisons cannot be interpreted quantitatively. SELECTIVITY RELATIONSHIPS AND TRANSITION STATE SHIFTS IN ARYLOLEFIN BROMINATION

Non-additivity of substituent effects

It is well known that the kinetic effects of several substituents on one or two aromatic rings are not additive. This is exemplified in the bromination of 1,l-diphenylethylenes, stilbenes and a-methylstilbenes. The presence of a substituent, particularly one capable of electron donation by resonance, on the aromatic ring so alters the charge distribution at the transition state that the second substituent in the other ring then interacts with a charge different from that which would prevail if the substituent were alone. This is expressed

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

257

by (37), where the reaction constant for the effect of Y in the presence of a px = pH

+ qa,

(37)

fixed substituent X, p x , is related to the o-constant of X. Equation (37) is mathematically deduced from (38), which describes the non-additive effect

in terms of different reaction constants for each of the two substituents, X and Y. The general structure-reactivity relationship for multiple substituent effects, (39), is readily obtained by combining (37) and (38). Non-additivity is therefore taken into account by the last term, which involves the coefficient q, described as the interaction constant (Lee, 1992).

Because of the complexity of the kinetic data for bromination when several pathways compete, this treatment has only been applied to olefins that react by the cationic pathway. The dependence of p x for a substituent Y on the other substituent X in the three types of diarylethylenes is shown in Table 15. The p-value for the variable group depends on the fixed substituent more in the 1,l-diarylethylene series (Fig. 11)(Hegarty et al., 1972)than for stilbenes and a-methylstilbenes (Argile and Ruasse, 1983). This is expected, since, for the first olefin, the two aryl rings are conjugated with the developing charge, whereas for the others, the second substituent, insulated from this charge by an incipient bromomethylene group, interacts more weakly with the first substituent. Consequently, the q-value, the interaction constant calculated by (37), is more negative for 1,l-diarylethylenes. Data for the ethanolysis of benzhydryl chlorides (Nishida, 1967), a reaction closely related to diphenylethylene bromination, can also be analysed using (37)-( 39). The resulting pH- and q-values, -4.39 and -2.2, are in the same range as those for electrophilic addition in methanol ( - 3.57 and - 1.55). The treatment of non-additivity has also been applied to a large variety of multiple substituent effects on various reactions (Argile et al., 1984) and, in particular, to the bromination of X,Y-disubstituted benzenes where two substituents on the same ring interact strongly (Dubois et al., 1972b); the interaction constant q = - 7.98, associated with a very negative p-value, - 12.05, is much higher than those found for the bromination of arylolefins. An extended form of (39) has been used to analyse kinetic substituent effects on bromination of alkenes GR,C=CR,Rb, where G is a conjugatively electron-donating group and R is alkyl (Bienvenue-Goetz and Dubois, 1981).

258

M.-F. RUASSE

Table 15 Non-additivity of multiple substituent effects: p-dependence on X for a substituent Y and interaction constants in arylolefin bromination in methanol at 25°C. 1,l-Diphenylethylenes" logky=H -px

X 4-OMe 4-Me H 3-C1 3-NO2

x'

2.27 3.03 3.57 4.08 4.65

- 1.55

Stilbenes (carbocation pathway)b logky=~ -px

H 4-C1 3-C1 4-NO2

Yd

6.95 5.58 4.62 3.27 2.27

4

-0.02

-0.41 - 0.66 - 1.36

5.52 5.63 5.70 5.90

-0.51

a-Me-stilbenes (tertiary pathway)* log kX=H -Pa

4-Me H 3-CF3

2.90 2.65 1.72

4.69 4.87 5.17

4-OMe 4-Me H

5.95 4.04 2.65

1.19 1.46 1.66

'Hegarty et al. (1972). *Ruasse and Argile (1983). 'With electron-donating Y only. dWith electron-donating X only.

It is reasonably assumed that the reaction of these ethylenic substrates occurs via a carbocationic Ca pathway (40) only, because of the nature of G

ELECTROPHILIC BROMINATION OF C=C

259

DOUBLE BONDS

-5

px -4

It I

I

0

rr*

*0.5

I

Fig. 11 Non-additivity of the X- and Y-substituent effects on the bromination rates of 1,l-diarylethylenes (Hegarty et al., 1972). px for the variation of Y when X is fixed is linearly related to o;, according to eq. (37).

(-OCOR, -OR, -OH). [It is noteworthy that the bromination ofenol acetates does not involve ester participation in the rate-limiting step and goes exclusively through the usual bromocation ( Bienvenue-Goetz and Dubois, 1978).] As for the reactivity-structure correlation of alkene hydration (Koshy et al., 1979), a;- and a:-constants are used to describe the effect of 01- and P-substituents respectively. The carbocationic character, common to the transition states of both additions, results in highly unsymmetrical 01- and B-effects. The general equation obtained from the data for bromination in methanol, (41), involves two interactive terms expressing the interaction

between the two a-substituents and between j?- and a-substituents respectively. This equation describes satisfactorily the rates of 30 alkenes covering a reactivity range of 8 log. units. It is interesting to compare (41) with (21) found for the hydration of analogous ethylenic compounds. Equation (21) does not imply any interaction terms, i.e. the p-values, p a and ps, are constant throughout the complete reactivity range. However, a more detailed analysis shows slight variations in p-values for hydration, which are concealed by the statistical treatment (Table 16). The different behaviour of these two electrophilic additions, both of which go through carbocations, has been

260

M:F.

RUASSE

Table 16 Reaction-constant dependence on substituent G in electrophilic hydration" and brominationb of alkenes GR,C=CR,Rb. Bromination G CF, H Ph OCOMe OH OEt

Hydration - 21

pa

- 11.8 - 12

- 7.4

8.6

- 3.2

-11

-

-6.5 - 4.2

Ps

-

11.8

- 9.2 - 5.0

Koshy et al. (1979). bBienvenue-Goetzand Dubois

( 198 1).

interpreted in terms of differences in transition state positions. More extensive comparison of data related to the reaction of similar olefins carried out later (p. 265) support:: this interpretation. Selectivity relationships and the Bema Hapothle in bromination

Equations (37)-( 39), where the non-additivity of multiple substituent effects is described by a cross-term, express correctly the rate data for bromination and other reactions of polysubstituted substrates. The question arises, therefore: has the interaction constant, q, any physicochemical meaning in terms of mechanism and transition state charge? To reply to this question, selectivity relationships (42)that relate the p-variation to the reactivity change and not to any substituent constant, have been considered (Ruasse et al., 1984). p x = alogkH

+b

(42)

The a-coefficient is related to q in (37) by (43). The plot corresponding to

the bromination data of Table 15, where results on styrenes, methylstyrenes and methoxystyrenes have been added, is shown in Fig. 12. Two discrete straight lines are obtained: line A (44) correlates styrenes and stilbenes; line B (45) 1,l-diphenylethylenes and methoxystyrenes. The difference between

ELECTROPHILIC BROMINATION

OF C=C DOUBLE BONDS

p = 0.46 log k H - 5.61

261

(45)

the two olefin groups, ArCR=CHR’, lies mainly in the nature of R, which is able to donate electrons by conjugation in set B but not in A. The conjugative ability of R enhances the sensitivity of p to the reactivity by a factor of about two. According to (46), reaction constants p are generally p=-

6 log k 60

considered as selectivity constants. The a-coefficients in (42) are then quantitative expressions of the effect of the reactivity-selectivity principle, RSP, as described by the Bema Hapothle (p. 209; Ruasse, 1988;Jencks, 1985). There is an inverse relationship between reactivity and selectivity insofar as both are related to shifts in the transition state position. The progress of the reaction at this transition state, a, is usually obtained from coefficients of Brransted or of other rate-equilibrium relationships which compare substituent effects on kinetics and thermodynamics. The p-values can also express this position if pk for rates and pt for equilibria of the same elementary step are available (47). Relationship (48), which gives the meaning of a as regards pk = apt

(47) (48)

Fig. 12 Selectivity-reactivity relationships in arylolefin bromination. Line A correlates the data for styrenes, stilbenes and their a-methyl derivatives, and line B those of 1,l-diarylethylenes and cc-methoxystyrenes (Tables 15 and 17).

262

M.-F. RUASSE

the transition-state position, is obtained by combining (42) and (47). Given CL = 6 log k / 6 log K , the a-coefficient from rates, ak,is related (49) to the same

coefficient from equilibria, a', and to the shift in the transition state position with the reactivity. In the absence of the a'-coefficient (p' = a' log K b), there is no direct way of separating the thermodynamic contribution to ak from the kinetic (transition state) one. However, the occurrence of two selectivity relationships in bromination [Fig. 12, (44) and (45)] affords the possibility of doing it. When R is a conjugated group, as in set B (45), thermodynamic and kinetic terms contribute to the a-coefficient, but in set A, where R is alkyl or hydrogen, the thermodynamic term is negligible with respect to the kinetic one. It can therefore be inferred that the smaller U-value corresponds to a transition-state shift with reactivity changes (6cr/6 log k ) , whereas the higher includes, in addition, the substituent effect on the stability of the intermediate (a' = 6p'/6 log K ) . This result is supported by the following two observations. Substituent effects on rates (Nishida, 1967) and equilibria (Mind1 and Vecera, 1972) of the heterolytic formation of benzhydryl cations, analogous to those obtained in the bromination of 1,l-diphenylethylenes, can be analysed in terms of selectivity relationships (50) and (51). Here ak is

+

pk = 0.52 log k - 2.10

(50)

p' = 0.34 log K - 0.44

(51)

markedly greater than a', showing elegantly that the second term of (49), i.e. a transition-state shift, is significant and adds to the first one, which is related only to the thermodynamic effects. Coming back to bromination, it is reasonable to suggest that the slope in (43), ak = 0.26, represents the transition-state shift with reactivity, whereas in (45)the a-coefficient is the sum of this effect and the thermodynamic contribution. On the other hand, transition-state positions in bromination can be evaluated from solvent effects and their Winstein-Grunwald rn-coefficients, since these latter are related mainly to the magnitude of the charge in the activated complexes (p. 274). The p- and rn-values for most olefins included either in selectivity relationship A (44) or in B (45) are compared in Table 17. The rn-value varies significantly with the reactivity as does p. Since rn-variations arise from transition-state shifts, p-variations necessarily come, at least in part, from the same effect.

ELECTROPHILIC BROMINATION OF C=C

263

DOUBLE BONDS

Table 17 Selectivity relationships: substitucnt" and solvent effects in bromination of arylolefins as indexes of transition state shifts with reactivity.

trans-Stilbene a-Me-stilbene Styrene trans-b-Me-styrene a-Me-styrene 1,l-Diphenylethylene a-OMe-styrene

-0.02 2.65 2.71 2.81 5.14 4.62 9.00

5.52 4.87 4.80 4.72 4.26 3.57 1.58

1.20' 1.03' 0.96' 1.01' 1.04' 0.45/

"For the carbocation pathway. bRuasse et al. (1984). 'Ruasse and Dubois (1975). dRuasse (unpublished results). 'Ruasse and Lefebvre ( 1984). IRuasse and Dubois (1984).

EARLY TRANSITION STATES IN ENOL ETHER HALOGENATION

Imbalance between polar and resonance efects in enol ether halogenation

Bromination rates of aliphatic enol ethers have been included in the interactive treatment of alkenes GR,C=CR,R,, with G being a conjugated group; most of them fit the multiparameter equation (41) satisfactorily. A more detailed analysis of reactivity-selectivity effects in the reaction of l-ethoxyethylene [22] and its a- and 8-methyl analogues [23] and [24] has been carried out, EtO EtO-CH=CH,

\

,C=CH,

Me/ c221

c231

EtO-CH=CHMe

c 241

taking the a- and 8-methyl rate ratios ka-Me/kHar,d kD-Me/kHas criteria of kinetic selectivity (Ruasse, 1985). Their bromination is diffusion-controlled in water but not in methanol and ethanol; iodination is merely fast and hydration is slow (Table 18). The selectivities, kar-Me/kH,towards the various electrophiles vary in rough agreement with RSP. They are similarly small for both halogenations, the rates of which differ by about 4 log. units, but this ratio is very large for hydration, the slowest addition. In bromination the a-methyl effect is noticeably smaller than observed for less reactive alkenes; ~ and for vinyl bromide for example, for styrene ( k = 8 x 10' M - s-') ( k = 1.8 x l O - ' ~ - ~ s - l ) i n m e t h a n o l , i t i 180and700respectively.Theeffect s

264

M.-F. RUASSE

Table 18 Reactivity, log k,” and selectivities, ka.Me/kH and k p M e / k H , of electrophilic additions to 1-ethoxyethylene.

EtOCH=CH, EtOC(Me)=CH, trans-EtOCH=CHMe krr-Me/kn

kp-Me/kn

Transition-stateindex‘

log k,,,b

log k,:

11.2 (8.34) 12.7 (9.53) 11.6 (8.69)

7.08 8.53 7.85 28

31 2.5

0.6

6

0.6

log kH,O+d

0.25 2.76

- 0.80

330 0.1 0.6’

a k i n ~ - l s - l in ’ water at 25°C. bValuescalculated from rates in MeOH, given in parentheses, and in EtOH using the Winstein-Grunwald relationship. ‘Ruasse (1985). dOyama and Tidwell (1976). ‘mwG-values for halogenations and Brransted cc-exponent for hydration. fKresge and Chen (1972).

of a P-methyl group on this addition is significantly smaller than that of an a-methyl group, indicating a dissymmetry in the charge distribution, as expected for a carbocationic transition state. But this dissymmetry is less important than that found for the slow vinyl bromide, for which k a - ~ e / k p -=~ e18. In addition, m-values for the two ether halogenations are markedly smaller than usual. In contrast, the Brernsted a-exponent for hydration (0.6) is in the same range as those measured for other alkenes (see Table 19), indicating that the proton is about half-transferred at the transition states. All these results show that the transition states for both halogenations with similar selectivities are unusually early whereas that of hydration is, as usual, midway on the reaction coordinate. It is concluded that the selectivitiesof electrophilic additions are not directly related to the reactivities but to the transition-state positions. Extensive comparison with similar data on the bromination and hydration of other ethylenic compounds bearing a conjugated group shows that this unexpected reactivity-selectivity behaviour can arise from an imbalance between polar and resonance effects (Ruasse, 1985). Increasing resonance in the ground state would make the transition state earlier and attenuate the kinetic selectivity more strongly than it enhances the reactivity. Hydration and halogenation probably respond differently to this imbalance.

Transition-state shifts with reactivity and selectivities in hydration and bromination of styrenes ArCY=CH2

A more extensive comparison between bromination and hydration has been carried out in the styrene series ArCY=CH,, where Y varies from H, Me

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

265

to OMe and OH, the rates of both additions increasing in this order (Ruasse and Dubois, 1984). For the two reactions, the rate-limiting step is the formation of a carbocation. In both cases, ring substituent effects are expressed satisfactorily by the Young-Jencks equation (33). The transition-state positions are given by m-values and Brarnsted exponents in bromination and hydration respectively. The overall results are collected in Table 19. The very small p- and m-values observed for the fast bromination of a-methoxystyrenes deserve comment since they are the smallest found for this electrophilic addition. The rates, almost but not quite diffusion-controlled, are amongst the highest. The sensitivity to polar effects of ring substituents is very attenuated but still significant; that to resonance is nil. These unusually low p-values for a reaction leading to a benzylic carbocation are accompanied by a very small sensitivity to the solvent. All these data support a very early transition state for this olefin series. Accordingly, for the still more reactive acetophenone enols, the bromination of which is diffusion-controlled, the usual sensitivity to substituents is annulled. For hydration (Dubois et al., 1981a), there is a significant decrease in the sensitivity to Y with increasing reactivity, but it is smaller than that for bromination. The p-values for these additions are linearly related to each other, but bromination is twice as sensitive to ring substituent effects compared with hydration (Fig. 13). However, constant Brarnsted a-exponents show that, in contrast to bromination, there is no marked shift in the transition state of hydration. It is therefore assumed that the p-variation in hydration comes only from a thermodynamic effect, related to a Y-dependent change in the stability of the intermediate, whereas in bromination, a transition-state shift adds to this latter effect, as expressed by (49)and (52), where log k, expresses the reactivity of PhCY=CH,. The second term in ( 5 2 ) is probably negligible in hydration apt --a-6Pk 6 log k, 6 log k,

+

6a pt 6 log k,

but not in bromination. This result would imply, in terms of the Marcus equation, that the intrinsic kinetic barrier is much higher in hydration than in bromination. In conclusion, bromination is a particularly attractive reaction for studying the origin of reactivity-selectivity effects in detail, since it is now well established that substituent and solvent effects arise not only from changes in the stability of the cationic intermediate but also from transition-state shifts, in agreement with the Bema Hapothle, i.e. RSP, Hammond postulate and Marcus effects.

Table 19 Substituent and solvent effects in bromination and protonation of styrenes ArCY=CH,.

H Me OMe OH

-4.80 -4.26( -3.2) - 1.85( - 1.5) 0 (0)

-4.80 -2.8 0 0

2.77 5.14 9.32 * 10

0.96 0.86 0.45 -

-3.6( -4.3) - 3.4( -4.05) -2.33( -2.89) - 1.57(- 1.9) ~~

~

- 3.4 - 2.4

-0.97 -0.75

-6.96 -4.02 1.74 3.24

-

0.6 0.6 0.6

~ _ _ _ _ _ _ _ _ _

"Ruasse and Dubois (1984). *Rate data for styrenes and a-Me-styrenes (from Durand et al., 1966) and for methoxy- and hydroxystyrenes (from Loudon and Berke, 1974). 'Values in parentheses are for bromination in water (Ruasse and Lefebvre, unpublished results). dGrunwald-Winstein coefficients for solvent effects. 'Values in parentheses are for protonation in MeOH (Toullec, 1979; Dubois et al., 1981b). IBr~instedexponents.

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

267

Y

-C 0

d

.

Me

0

.-C

5.

n

-

Me0 0. 0

I pH*[ Hydration

Fig. 13 Comparison of p values for bromination and hydration of styrenes XC,H,C( Y )=CH, with variable Y. Selectivity coefficients for bromination depend on Y twice as much as for hydration (Ruasse and Dubois, 1984).

6

Solvent effects and solvation in brornination

Along with the previous approaches for evaluating transition-state shifts from substituent effects, solvent effects have frequently been referred to as indexes of charge development in bromination. This is not surprising, since physical organic chemistry considers that the sensitivity of any reaction rate to the solvent or to a substituent arises mainly from changes in charge separation along the reaction pathway. However, specific solvent/transition state interactions make this generality particularly relevant to bromination. It was shown quite early (Garnier et al., 1971) and confirmed later (Ruasse and Motallebi, 1988),from solvent isotope effects ( k M e O H / k M e O D ) on the rates of 1-pentene bromination and from a linear relationship (53) between these AG& = 0.86 AG,,,

+ 12.3

(53)

rates and the bromide transfer energies in a series of water-methanol mixtures, that the main role of the solvent is electrophilic solvent assistance to bromide ion departure.

M:F.

268

RUASSE

In other words, the magnitude of protic solvent effects is directly related to the magnitude of the negative charge on the developing bromide ion at the transition state. Since the positive charge is necessarily equal to the negative charge, solvent effects provide a simple measurement of the charge separation. Accordingly, two kinds of experimental data, kinetic solvent isotope effects and the m-values of Winstein-Grunwald correlations, have been used to obtain transition state indexes for a large variety of ethylenic compounds. However, the results from substituent and solvent effects for any olefin are not as consistent as expected, since both are complicated by other factors; these are mainly charge delocalization for the first and nucleophilic solvent assistance for the second. KINETIC SOLVENT ISOTOPE EFFECTS

Most of the available KSIEs measured in methanol, ethanol or acetic acid and their deuteriated analogues are shown in Tables 20 and 21. They must be compared with the &- factor [ 1.35 and 1.27 in methanol and ethanol, Table 20 Solvent effects in alkene bromination: dependence of the electrophilic (KSIEs) and nucleophilic assistances ( R ) on the alkene.

KSIE" Ad=CHZd*' t-Bu-i-PrC=CHZf Me,C=CMe-i-Prf cis-MeCH=CH-t-Bu'

Branched alkenes 1.30(EtOL) 1.11 1.32(MeOL)g 1.08 1.07 1.02

0.9 1.4 1.o 1.5

5.62 2.29 6.38 4.04

PhCH,CH=CH,' n-PrCH=CH,' cis-EtCH=CHEt Me,C=CMeZf

Linear alkenes 1.37(MeOL) 0.80 1.35(MeOL) 0.92 1 . 2 3 ( A ~ o L ) ~ 0.92 0.96

8.3 6.2 4.1 3.3

1.72 2.60 4.54 7.16

0.8 0.6 0.4

7.40 5.76 3.15

Ad=CMe,' Ad=CMe-i-Pr' Ad=CH-t-Bu'

f

Congested alkenes -

1.13(EtOL) 1.29(MeOL)

0.63 0.76 0.85

Kinetic solvent isotope effect as a measure of electrophilic assistance to bromide ion departure; limiting values: &,- = 1.35 in MeOL and EtOL at 25°C. bObtained from rate data in ethanol, methanol and their aqueous mixtures using Bentley's Y, scale; its decrease corresponds to the involvement of nucleophilic assistance. 'R = ( kaqEtOH/kAcOH),,as a measure of nucleophilic solvent assistance. dModel for a limiting bromination mechanism. 'Ruasse et al. (1991). 'Ruasse and Zhang (1984). gArgile and Ruasse (to be published). hModro ef al. (1979). a

ELECTROPHILIC BROMINATION

OF C=C DOUBLE BONDS

269

Table 21 Solvent effects in bromination of conjugated olefins: transitionstate shifts and nucleophilic solvent assistance.

Styrened a-Me-styrenee a-OMe-st yrene’ Stilbened cr-Me-stilbene’ 1,l-Diphenylethylene“ EtOCH=CH,g

-

1.04(MeOL)’ -

1.02(MeOL)/ -

0.80 0.81 0.36 0.86 0.83 0.83 0.48

27 5.4 -

100 5.9 2.6 -

3.18 5.14 9.3 1 1.04 2.65 4.62 8.35

Kinetic solvent isotope effect as a measure of electrophilic solvent assistance to bromide ion departure; limiting value: & - = 1.35 in MeOL. bFrom Y,, and kinetic data in water, methanol, ethanol and their aqueous mixtures. ‘( kaqEtOH/kAcOH)Y;measurement of nucleophilic solvent assistance. dCalculated from data in Ruasse and Dubois (1975) and Ruasse et al. (1978). ‘Ruasse and Lefebvre ( 1984). ’Ruasse and Lefebvre (unpublished results). @Ruasse( 1985). a

respectively (Ruasse and Motallebi, 1988)], which is the limiting KSIE value corresponding to the effect on the solvation of a fully developed bromide ion. It is noticeable (Table 20) that for most aliphatic alkenes, the KSIEs are very high, close to & - . These results are valuable evidence for late transition states [25] in the bromination of these olefins. In contrast, the

c251 KSIEs for the reaction of aromatic olefins, 1,l-diphenylethylene and or-methylstyrene (Table 21 ) are significantly smaller; they can be related to transition states earlier than those in the aliphatic series. Unfortunately, for the reactions of highly reactive aromatic olefins or enol ethers, whose low sensitivity to solvent and substituent effects indicates very early transition states, there are not enough KSIE data to confirm this conclusion. The only series of alkenes that show anomalously low RSIEs is that of highly congested adamantylidenealkanes (last rows of Table 20). The decrease in the isotope effect, associated with particularly small m-values and the absence of nucleophilic solvent assistance, can be attributed to reversible

270

M.-F. RUASSE

formation of strained bromonium ions, the nucleophilic trapping of which is strongly inhibited (p. 273). THE Ysr SCALE FOR BROMINATION

The second series of data on protic solvent effects in bromination that are related to transition states comprises the m-values of solvent-reactivity correlations. First, it is important to underline that Y-parameters, the solvent ionizing powers, established from solvolytic displacements, work fairly well in this electrophilic addition. This is expected since bromination, like S, 1 reactions, leads to a cation-anion pair by heterolytic dissociation of the bromine-olefin CTC, a process similar to the ionization of halogenated or ether derivatives (Scheme 14).

R-X

+

R',

X-

Scheme 14

The first Winstein-Grunwald correlations for bromination (Garnier and Dubois, 1968; Ruasse and Dubois, 1975) used the initial Y-values derived from t-butyl chloride solvolysis (Fainberg and Winstein, 1956). Since that time, it has been recognized that this Y-defining reaction does not proceed through a pure SN1 mechanism (Raber et al., 1970). More recently, Bentley and Llewellyn ( 1990) established new Y,-scales from 2-adamantyl substrates involving various leaving groups X. These scales correspond to an ionization process where the solvent interacts with the transition state electrophilically but not nucleophilically, back-side obstruction of the breaking bond by the adamantyl group inhibiting nucleophilic attack by the solvent. The analysis of these Y,-scales (Bentley et al., 1984) in terms of the Kamlet-Abboud-Taft equation (54)(Kamlet et al., 1981), which dissects the solvent effect into log (ks/k,)

= S~T*

+ uu + bp

(54)

three contributions (dipolarity, z*, hydrogen-bond donor a and hydrogenbond acceptor p) shows that Y, describes mainly the solvent dipolarity, often called the medium effect. However, a significant contribution from the hydrogen-bond donor ability cannot be excluded, since the Y,-values depend slightly on X, the leaving

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

27 1

group. As regards bromination, the Y,,-scale derived from either 1- or 2-bromoadamantane solvolysis (Bentley and Carter, 1982) is the most relevant since the leaving group is a bromide ion in both reactions. In addition to electrostatic medium effects and to electrophilic assistance described by Y, nucleophilic solvents can assist positive charge development in heterolysis of secondary, and sometimes tertiary, substrates via an S,2 (intermediate) mechanism (Bentley et al., 1981). Equation ( 5 5 ) , involving log ( k s / k s o )= rnY + IN

(55)

both ionizing power and nucleophilicity N , must therefore be considered in its totality (Schadt et al., 1976). A rigorous approach to the several roles of the solvent in ionization reactions must therefore involve rate measurements in a number of media of variable Y and N . In particular, fluorinated solvents with very low nucleophilicities must be added to the usual nucleophilic alcohols in order to evaluate the solvent involvement described by 1N.This cannot be done systematically for bromination because the rates for most olefins in trifluoroacetic acid, trifluoroethanol or hexafluoroethanol are too fast to be measured. Consequently, in order to obtain information about the several solvent contributions, the following procedure has been used (Ruasse et al., 1991). The rn,,-values are first obtained using YB,-parameters(Bentley and Carter, 1982)of solvents of closely similar nucleophilicities (H,O, EtOH, MeOH and their aqueous mixtures). These values depend both on the nucleophilic solvent involvement and on the magnitude of the transition-state charge. An increase in nucleophilic assistance and an early transition state decrease mBr, as compared with its maximum value for the unassisted formation of a bromonium ion via a late transition state. In order to determine whether smaller rn-values must be attributed to charge decrease and/or to nucleophilic solvent involvement, complementary data must be obtained. Assistance can be estimated by R-ratios (Fig. 14), which compare the rates in two solvents of similar ionizing power but different nucleophilicities, such as the acetic acid-aqueous ethanol couple (Bentley and Schleyer, 1976). When measurements are possible in trifluoroethanol, TFE, R-values can also be obtained from the TFE-aqueous methanol pair in a higher reactivity range. Transition-state charges are available from KSIEs. Consequently, for the bromination of a given olefin, most of the relevant information about solvent effects can be obtained by combining KSIE, rnBr and R . The rigorous analogy between electrophilic halogenation and solvolytic displacements was recognized only recently (Ruasse et al., 1991).Consequently, for most of the previously published solvent effects, the above procedure has not been applied systematically.Winstein-Grunwald, YW-G,parameters have

M.-F. RUASSE

272

8

6 .

PhCHLCH=CH2 rn =0.8

L .

2 .

L

-2

-I

0

I

2

3

4

Fig. 14 Typical log k / Y,, plots for assisted and unassisted alkene brominations. Allylbenzene and 1-pentene, less crowded than cis-methyl-t-butylethylene and methylideneadamantane, exhibit the smallest m-values. The points corresponding to acetic acid (0) and trifluoroethanol (A),two weakly nucleophilic solvents, are below the regression line for water, methanol, ethanol and their aqueous mixtures ( 0 )of similar nucleophilicity. In contrast, they are on the line for the branched alkenes where steric crowding inhibits nucleophilic assistance by alcoholic solvents (Ruasse et al., 1991, Ruasse and Motallebi, 1991).

been used generally to obtain mW-G coefficients. Since there is a fairly linear relationship between Yw-G and Y,, for nucleophilic aqueous ethanol and methanol mixtures, mBr can be estimated from mw-G = 1.25~1,~.But these calculated m,,-values are not compatible with the method described above, because non-nucleophilic solvents, acetic acid in particular, are generally included in the mW-G calculations. Consequently, data shown in Tables 20 and 21 are not quite those given in the references quoted; they have been recalculated in agreement with the more recent procedure. VALUES OF m,, IN ALKENE BROMINATION: NUCLEOPHILIC AND ELECTROPHILIC ASSISTANCE BY PROTIC SOLVENTS

The first step in the interpretation of m,,-values has consisted in searching for an alkene for which nucleophilic solvent assistance is impossible. Methylideneadamantane, in which steric constraints can restrict nucleophile

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

273

approach to the developing bromonium ion, was chosen by analogy with 1- or 2-bromoadamantane, whose solvolyses define the YBr-scale(Ruasse and Motallebi, 1988). With this alkene, a limiting mBr-valueof 1.1 is measured from ethanol, methanol and their aqueous mixtures. Similarly high mBr are obtained (Table 20) when the double bond is substituted by branched groups. The solvent is not nucleophilically involved since the R-ratios are close to unity. Their transition states are very late, as shown by the large KSIEs. For less congested alkenes, values of mBr are significantly smaller; they are associated with R-values markedly greater than unity, and the transition states are still very late. Consequently, the attenuation of mBr does not arise from a smaller charge development in the activated complex but from nucleophilic participation of the solvent [26]. It is noteworthy that this specific

" /

---Br---LOS

solvent-transition-state interaction seems to be reactivity-dependent; the higher the reactivity, the smaller the assistance. This agrees with the usual interpretation of charge stabilization in terms of electronic demand; the greater the stability of a cationic species, the lower its demand on substituents or solvent to assist the charge development. In the solvolysis of secondary alkyl sulfonates, competition between nucleophilic solvation and electron donation by the substituents results in a significantly solvent-dependent p*, which varies from - 9 to - 1 on going from the non-nucleophilic hexafluoro-Zpropanol to 80% aqueous ethanol (Bentley et al., 1981). In contrast, the p*-invariance for alkene bromination in H,O, M70, MeOH and AcOH [equations (22)-(25)] seems to imply a perfect balance between the two types of charge stabilization. However, this conclusion is probably risky since the nucleophilicities of the solvents implied in (22)-(25) do not vary markedly. Data in non-nucleophilic fluorinated solvents would therefore help to fill the gap in our knowledge. Finally, the last group of alkenes in Table 20 (congested alkenes) behaves very differently as regards solvent effects. The mBr,R and even KSIEs are systematically smaller than those observed for the two prevfous series. The attenuation of these coefficients can be reasonably attributed neither to earlier transition states nor to increases in nucleophilic solvent assistance. As described in the paragraph on return (p. 279), this trend is more consistent

274

M.-F. RUASSE

with the kinetic barrier for the product-forming step being higher than that of bromonium ion formation; in other words, return could be significant in the bromination of highly congested alkenes. To summarize, for the bromination of most alkenes, transition states are late and closely resemble the bromonium ions. The m,,-values reflect also the highly charged character of the activated complexes, since they are always in a range (0.8- 1.1) that is considered in solvolysis as indicating cationic intermediates. However, as in S,2( intermediate) solvolysis, mBr varies significantly because of nucleophilic solvent assistance. The greater the assistance, the smaller the mBr-values. In particular, this latter solvent contribution strongly depends on the crowding of the double bond and disappears when there are moderately bulky substituents. VALUES OF rnB, AND TRANSITION-STATESHIFTS IN BROMINATION OF CONJUGATED OLEFINS

In contrast with simple alkenes, mBr varies markedly with the structure of the olefin when a substituent is conjugated with the double bond (Table 21). There is a rough inverse relationship between mBr and log kWeOH (Fig. 15).

0.51,

, 3

,

I

5

,

,~

7 log kX,MeOH

Fig. 15 Reactivity dependence of rn, the Winstein-Grunwald coefficients for solvent effects, in the bromination of monosubstituted 1,l-diphenylethylenes (Ruasse and Lefebvre, 1984).

ELECTROPHILIC BROMINATION OF C=C

275

DOUBLE BONDS

This result, associated with those on substituent effects, supports previous conclusions to the effect that the position of the transition state depends on the reactivity in agreement with RSP. In particular, stabilization of the intermediate as a result of conjugation, such as that in the reaction of enol ethers, makes the transition state very early. The few available KSIEs also suggest that the transition states for aromatic series are earlier than those for alkenes. The most striking finding of Table 21 concerns nucleophilic assistance. The R-values are markedly greater than those found for simple alkenes. In particular, R for stilbene is as high as 100, whereas that of allylbenzene, whose reactivity is in the same range, is only 8. This can be interpreted in terms of a different charge distribution. Whereas the transition states for alkenes are bromonium-ion like, those from aromatics resemble carbocations. The charge in the latter case is on only one carbon atom, so that assistance by the solvent is more efficient than when it is distributed over a three-membered bromonium ring. This feature can be counterbalanced by steric restrictions to solvent approach. In this respect, it is noticeable that the reactions of cc-methyl olefins are only weakly assisted, as compared with those of the parent olefins. Finally, smaller R-ratios can also arise from charge delocalization in the aromatic ring; for 1,l-diphenylethylene, DPE, the assistance is less than for a-methylstyrene, EMS, which is of similar reactivity. All these factors, namely, intermediate stability, cationic charge distribution, delocalization by resonance and steric inhibition, can influence the values of both R and mBr. To distinguish between these several contributions, a systematic study of ring substituent effects on rn and R has been carried out in the DPE and a-MS series (Table 22; Ruasse and Lefebvre, 1984). In both cases, the solvent coefficients are observed to be substituent-dependent. The marked decrease in mBr and R on going from electron-acceptors to donors is greater in a-MS than in DPE. This suggests that charge delocalization by Table 22 Substituent and solvent effects in the bromination of 1,l-diphenylethylenes, DPE, and a-methylstyrenes, a-MS." 4-CF3

3-CF3

H

4-OMe

6.5 0.90 2.59

-

-

2.6 0.83 4.62 5.4 0.81 5.14

1.5 0.49 6.95 1.7 0.54 7.82

-

-

a

Ruasse and Lefebvre (1984).

-

34.2 1.03 2.96

276

M.-F. RUASSE

the second phenyl group of DPE contributes significantly to the attenuation of nucleophilic assistance and therefore of mBr. Moreover, the solventindependence of p* found for bromination of simple alkenes does not exist for conjugated olefins; for example, the p"-values for a-MS bromination are -5.76 and -4.26 in acetic acid and methanol respectively. It can be concluded that mBr depends on the magnitude of the charge at the transition state and also on its delocalization either by the substituents or by the solvent. It therefore seems difficult to separate these effects, since R, the measure of solvent assistance, depends also on the same factors. The idea that transition-state shifts contribute to m-variations is supported by substituent effects. Consequently, it would be useful to obtain p-m correlations to compare the influence of the solvent and the substituents in determining the position of the bromination transition state. BROMINE-CATALYSED BROMINATION IN NON-PROTIC AND HALOGENATED SOLVENTS

Most brominations used for synthetic purposes are carried out in halogenated solvents. There are, however, only a few mechanistic studies in these media, since it was difficult to obtain reproducible rate constants. Even now that reliable procedures have been published (Schmid et al., 1972; Bellucci et al., 1981),the upper limit of the rate constants available is about 105-106 M - ~ S - ~ since only spectroscopic techniques can be used. The most significant difference between brominations in protic and non-protic solvents concerns the kinetic law. Whereas in protic media the reaction is first-order in bromine, in halogenated media it is second-order (Bellucci et al., 1980).CTC ionization is electrophilically assisted by hydrogen bonding by a protic solvent to the leaving bromide and leads to a bromonium- bromide ion pair. In non-protic media, assistance to the bromination step is provided by a second bromine molecule, leading to a bromonium-tribromide ion pair. In other words, in protic media bromination is solvent-assisted (56) while in halogenated media it is bromine-catalysed (57).

\C'

Br,

+ Br,

\ / +

(f+>Br, Br;

(57)

,

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

277

Since no solvent molecule seems to be involved in the rate-limiting transition states of bromination in non-protic solvents, only the electrostatic character of the medium should influence the reaction rates. Consequently, there have been some attempts to correlate the kinetic solvent effects with the Kirkwood function, it being assumed that the solvent can be considered as an isotropic continuum (V'yunov and Ginak, 1981). Such attempts either failed or covered very narrow reactivity ranges. A fairly linear Kirkwood relationship was obtained recently (Bellucci et al., 1985b); it correlates the bromination rates of cyclohexene in 1,2-dichloroethane-chloroformmixtures. A variation in the dielectric constant from 4 to 10 induces a reactivity change of two orders of magnitude. Data obtained in other halogenated solvents cannot be included in this correlation, which is unique at present. Nevertheless, and despite the paucity of relevant data on both solvent and substituent effects on bromination rates in non-protic solvents, it seems reasonable to conclude that bromine addition depends mainly on the bulk medium polarity. However, this non-specific solvent property cannot be the only one responsible for the rate variations. According to (57), the main driving force for the reaction in non-protic media is the formation of a tribromide ion from bromine and the developing bromide. Kinetic (Ruasse et al., 1986) and thermodynamic (Bienvenue-Goetz et al., 1980) data on equilibrium (58) are therefore relevant to the effect of non-protic solvents on bromination rates. Br,

kr + Br- e Br; kr

Large solvent effects on the formation constant ( K = k,/k,) of the tribromide ion are observed (Table 23). The K-variation has been analysed in terms of the free energies of transfer of the bromide ion, AGtr(Br-), from acetonitrile to the appropriate solvent. Parker and Alexander ( 1968)assumed a linear relationship between AGtr(Br-) and AGf(Br;), the energy of formation of Br; according to (58), as expected if the solvation energy of neutral bromine is the same as that of the large and polarizable tribromide ion, (59). However, this assumption does not work. It was shown later that AG,(Br;)

= - AGJBr-)

+ [AG,,(Br;)

- AGtr(Br2)]

(59)

solvation of free bromine by electron-donor solvents cannot be neglected (Bienvenue-Goetz et al., 1980).A correlation (60) where this effect is expressed AG,(Br;)

= -

1.21ACt,(Br-)

+ 5.55g - 2.16

(60)

M.-F. RUASSE

Table 23 Formation constants of tribromide ion and transfer energies of bromide ionnsbat 25°C. KIM-'

Me,CO" CICH,-CH,CI~ CH,ClZb C~,CH-CHC~,~ MeCHClZb CHCl,b MeNO," MeCN" HCONMe," EtOH" MeOH" H,O"

2x >2 x >2 x 1.9 x >2 x 1.2 x 1.6 x 1 x 2x

109 107 107 105 107 105 107 107 106

x 102

1.7 x 10' 16

AGtr(Br-y

kcyclohexene

b,d

2.6

-

- 1.6

0 0.7 - 2.9 - 4.8 - 7.4

"Bienvenue et al. (1980). bBellucci et al. (1985a). 'In kcal mol-', relative to MeCN. dRate constant of cyclohexene bromination at 25°C.

by fl, the electron-donor ability of a solvent (Kamlet et al., 1981), describes the solvent dependence of K fairly well. Unfortunately, this equation is useless for halogenated media, which do not exhibit donor capability and which provide little or no solvation of the bromide ion. More relevant to the bromination mechanism could be the linear relationship (61) which has been found between the rates of Br, formation and the solvation energies of bromide in protic solvents (Ruasse et al., 1986). But again, appropriate log ( k , / k , ) = -0.07AGt,(Br-)

(61)

data are not available for non-protic solvents. It therefore turns out that a quantitative description of halogenated solvent effects on bromination rates is still inaccessible.

SOLVATION, THE DRIVING FORCE OF ELECTROPHILIC BROMINATION

Solvation is the main driving force of bromination (Ruasse and Motallebi, 199 1), since this electrophilic addition is impossible, or at least extremely 1977; difficult, in the gas phase (Angelini and Speranza, 1981; Staley et d., Sen Sharma et al., 1985). It has been calculated (Yamabe et al., 1988) that

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

279

more than 60 kcal mol- would be necessary to form a bromonium ion from ethylene and bromine; that is, the bromination rate constant of ethylene at M - ' s-'. However, in 25°C in the gas phase would be as small as water this constant is found to be 4 x lo5M - s- ' at 25°C (Bienvenue-Goetz and Dubois, 1968), which corresponds to an activation energy less than 10 kcalmol-'. In protic solvents the m,,-values discussed above show that electrostatic medium effects and electrophilic assistance to bromide ion departure are the main rate-determining factors. Free energies of bromide solvation by alcohols and water are in the range of 56-61 kcalmol-' at 25°C (Abraham and Liszi, 1978). Most of this energy contributes to the bromination rates, as shown by the high values of KSIEs (p. 268). Nevertheless, since these calculations are only approximate, it is hazardous to conclude that the medium effect is negligible. Moreover, nucleophilic protic solvents can assist positive charge development in the rate-limiting transition states. However, this contribution provides only a small to moderate acceleration, the magnitude of which depends on the double-bond substituents (p. 272). It is noteworthy that these several solvent roles are closely similar to those found in solvolytic reactions via carbocationic intermediates (Bentiey and Llewellyn, 1990). This is not surprising, since the main microscopic event of both classes of reactions is heterolysis, either of a Br-Br or a C-X bond, which seems similarly solvent-dependent. In halogenated solvents, catalysis by a second bromine molecule, which assists the Br-Br bond heterolysis, is the main driving force. The role of the solvent is electrostatic, but the absence of an extensive Kirkwood relationship suggests that there is some other kind of contribution (Bellucci et al., 1985b).

'

7

The reversible formation of bromonium ions

For a long time, it was considered that the formation of a bromonium ion from olefin and bromine is irreversible, i.e. the product-forming step, a cation-anion reaction, is very fast compared with the preceding ionization step. There was no means of checking this assumption since the usual methods-kinetic effects of salts with common and non-common ions-used in reversible carbocation-forming heterolysis (Raber et al., 1974) could not be applied in bromination, where the presence of bromide ions leads to a reacting species, the electrophilic tribromide ion. Unusual bromide ion effects in the bromination of tri-t-butylethylene (Dubois and Loizos, 1972) and a-acetoxycholestene (Calvet et al., 1983) have been interpreted in terms of return, but cannot be considered as conclusive.

280

M.-F. RUASSE

A preliminary indication that bromonium ions could be formed reversibly was provided by the reaction of adamantylideneadamantane (p. 249) leading to a highly stable bromonium-tribromide ion pair that readily releases bromine and the initial alkene (Strating et al., 1969). However, the first evidence for possible return came from the acetolysis of 2-bromocyclohexylbrosylate in the presence of bromide ions. It was shown (Brown et al., 1984) that the cyclohexylbromonium ion intermediate is able to release bromine. The drastic reaction conditions (high temperature, long duration and high bromide concentrations) cast some doubt on the generality of this observation. In fact, the analogy between the mechanisms of heterolytic nucleophilic substitutions and electrophilic bromine additions, shown by the similarity of kinetic substituent and solvent effects (Ruasse and Motallebi, 1991),tends to support Brown’s conclusion. If cationic intermediates are formed reversibly in solvolysis, analogous bromocations obtained from bromine and an ethylenic compound could also be formed reversibly. Nevertheless, return is a priori less favourable in bromination than in solvolysis because of the charge distribution in the bromocations. Return in bromination implies that the counter-ion, a bromide ion in protic solvents, attacks the bromine atom of the bromonium ion rather than a carbon atom (see [27]). Now, it is known (Galland et al., 1990) that the charge on this bromine atom is very small in bridged intermediates and obviously nil in p-bromocarbocations [281. \ /

\cI+ ,Br,n Br

\ \

/

‘C + c\ +\

I1

-C-Br

9

Br-

I

RETURN IN HALOGENATED SOLVENTS

Brown’s result was supported by later experiments in which bromonium ions were generated by bubbling gaseous hydrobromic acid through a solution of bromohydrins in halogenated solvents. Under these conditions, bromine is eliminated as it is formed, so that the resulting alkene is observed directly (Scheme 15). This method has been applied to the bromohydrins derived from cis- and trans-stilbenes (Scheme 16) and from 5H-dibenzo [a,d] cycloheptene and -azepine systems ([29a] and [29b] respectively; Scheme 17), in which steric constraints should favour elimination (path a ) as against substitution (path b).

ELECTROPHILIC BROMINATION OF C=C

2

28 1

DOUBLE BONDS

J

Br,+)=(

1

Br

-ABr

Scheme 15

Br\

,Ph

Ph

Br Ph (12%)

Ph Scheme 16

As shown in Scheme 16, erythro-2-bromo- 1,2-diphenylethanol readily gives meso-1,2-dibromo-l,2-diphenylethaneand substantial amounts of transstilbene (Bellucci et al., 1987). The slower reaction of the threo-analogue does not lead to cis- but to trans-stilbene arising from the acid-catalysed cis-trans isomerization of the initially formed olefin. In order to avoid this complication, Bellucci et al. (1988, 1991) studied the reaction of the bromohydrins derived from cyclic compounds [291 where the conformation of the two aromatic rings is maintained by a methylene [29a] or a nitrogen bridge [29bl (Scheme 17).The corresponding dibromides [301 and ethylenic compounds [31] are obtained in ratios [30]/[31] of 9/1 and 3/7 from the reaction of [29a] and [29b] respectively, with HBr in carbon tetrachloride, i.e. there is more return from bromonium ion pair [32b] than from [32a]. This trend is attributed to differences in the extent of bromine bridging in [32] being greater when Z is NCOCl than when it is CH,. The more electron-donating is Z, the less is the bromine bridging. Moreover, the yield of [31b] from [29b] is highly solvent-dependent: 30, 50 and 70% in 1,2-dichloroethane, chloroform and tetrachloride respectively. The less polar the solvent, the less stable the ion-pair [32] and the more return there is. These results show unambiguously that bromonium ions can be attacked

282

M.-F. RUASSE

,Br. + ,Brc291

/ I

~321

a: Z=CH, b: Z=NCOCI

c311

c301 Scheme 17

by bromide at the bromine atom to give free bromine and olefin. However, in the absence of data on the magnitude of bromine bridging in [32], the importance of return in the bromination of olefins [311 cannot be determined. RETURN IN PROTIC SOLVENTS

If the formation of bromination intermediates is reversible, the experimental rate constants obtained by following bromine uptake are not those of the first ionization steps. It is therefore important to know whether return, shown to occur in halogenated media, can also occur in protic media, in which most of the kinetic data have been measured and structure- or solvent-reactivity relationships established. To obtain data on reversibility in these media, the reactions of two kinds of congested alkenes, adamantylidenealkanes (Ruasse et al., 1991) and tetraisobutylethylene (Brown et al., 1990), have been investigated. It was assumed that crowding of the bromonium ion intermediate can favour return by inhibiting its nucleophilic trapping, i.e. by enhancing the energy barrier of the final, product-forming, step (Fig. 10). Adamantylideneadamantane bromonium ion (Strating et al., 1969) reacts by returning to the initial alkene and bromine only, whereas methylideneadamantane bromonium ion goes on to bromination products only (Ruasse and Motallebi, 1988). It was therefore hoped that the introduction of branched substituents (smaller than adamantyl) into methylideneadamantane would slow the product-forming step enough to make its barrier higher than that of return but not enough to inhibit it totally.

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

283

As said before, the comparison of solvent effects on the reaction of Ad=CRR’ (R and/or R’ # H ) [33] with those for Ad=CH, and other less

a: R = R = M e b: R=t-Bu, R ’ = H c : R=i-Pr, R’=Me

TIBE

C181

C331 crowded alkenes shows that return occurs for [33) only. The association of small m,,-values (0.8 instead of 1.1) with small kinetic solvent isotope effects, KSIEs (1.1 instead of 1.3), and small R-values (0.6 instead of 6-8; Table 20) is only observed for these congested alkenes. Small R-values are expected since nucleophilic solvent assistance is impossible. Small mBr and KSIEs, indicating a smaller than usual negative charge on the counter-bromide, agree fairly well with a mechanism involving return as shown in Fig. 10B. If the transition state of the product-forming step is of higher energy than that of the ionization step, the kinetic data and the coefficients deduced therefrom are related not only to the ionization process but also to the last step as shown in (62) and (63). Since step kN is a cation-anion reaction, there is a charge decrease on going from I, its ground state, to TSN, its transition state, so that mN is necessarily negative. Consequently, the experimental m-value is smaller than mi whose magnitude is that of alkenes which react irreversibly. The significantly smaller KSIEs are also consistent with a charge decrease on the bromide, as is expected on going from I to TSN.

k

= (ki/k-i)kN

m = mi

+ mN

(63)

Evidence for a reversibly formed bromonium ion in the bromination of [ 181 in acetic acid is provided by the unexpectedly high kinetic isotope effect, KIE (Brown et al., 1990). When the eight allylic positions of [ 181 are deuteriated, the bromination rate constant decreases by a factor of 2.3. This value is too high to be attributed to a usual secondary KIE, and is more consistent with a primary effect. This result implies that the allylic protons are involved in the rate-limiting step, which cannot therefore be the bromoniumion-forming step. It has been shown that halogenation products of congested alkenes arise from a rearrangement of their halonium ions induced by halide

284

M:F.

RUASSE

attack on allylic hydrogens (Mayr et al., 1986; Meijer et al., 1982). Although the bromination products of [33] and [18] have not been identified, the results, small KSIEs and high KIE, respectively, agree fairly well with this mechanism and with the fact that the allylic rearrangement is energetically more difficult than the usual bromonium trapping by nucleophiles. Consequently, the product-forming step is rate-limiting for the bromination of these congested alkenes. The present status of return in bromination can be summarized as follows. In protic solvents there is evidence that bromonium ions are formed reversibly when they are highly congested. In the absence of crowding, no experimental data support return but none exclude it either. When bromination intermediates are a-bromocarbocations, it is highly improbable that they are formed reversibly, since the bromine atom bears no charge. In halogenated solvents the results indicate that return can occur, even for the uncongested stilbenes. Unfortunately, its importance, as measured by the k-,/kN ratio (Fig. lo), cannot be estimated. It must be noted that Bellucci’s experiments prove only that return is possible, but do not demonstrate conclusively that it occurs in bromination, since reversibility is controlled by the relative energy levels of TS, and TSN which can be affected by the reaction conditions. Now, these conditions are not the same for nucleophilic substitution on bromohydrins and for bromine addition; in particular, the counter-ions, Br- and Br; respectively, can alter the lifetime of the intermediate and thus control its partitioning between return and nucleophilic attack. Reversible formation of the ionic intermediates results from a high energy barrier for the last, product-forming, step. It is therefore readily understood that crowding of the bromonium ion promotes return. It is more difficult to understand why this barrier is high in the absence of crowding in halogenated solvents. A reasonable interpretation based on the weakly nucleophilic character of the counter-ion, the tribromide ion, has been suggested; before reacting with the bromonium ion, tribromide has to dissociate at least partly into nucleophilic bromide and free bromine, a process that is quite slow in these solvents (Ruasse and Motallebi, 1991). A possible mechanism is proposed in (64). \C/ (bBr,

F\

+ Br,

\ / F

T>r,

F\

\ /

Br;

T>Br, Br-, Br,

F\

+P

(64)

In conclusion, the reversibility of bromonium ion formation is at present inferred from particular experiments only; nothing allows us to conclude that this mechanistic feature is general. However, when nucleophilic trapping

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

285

of the intermediate is likely to be difficult, kinetic data must be interpreted with caution because they are not necessarily related to the ionization step alone. 8

Concluding remarks

There are many significant and coherent data on the mechanism of free bromine addition to ethylenic bonds. The relative energetic contributions of the three elementary steps of the overall reaction and their dependence on the substituents and the solvent are now well known. It appears that in most cases kinetic data are mainly related to the ionization step. The preliminary formation of bromine-olefin charge transfer complexes, equivalent to encounter complexes, does not contribute significantly to the overall kinetic barrier, and is much less affected by the substituents (Ruasse, 1990) and the solvent (Brown et al., 1990) than the subsequent cation-forming step. Apart from well-identified exceptions-non-protic solvents (Bellucci et al., 1988, 1991) and highly congested double bonds (Brown et al., 1990; Ruasse et al., 1991)-the last, product-forming, step is very fast and the ionic intermediates are formed irreversibly. Thus the more recent results do not require major alteration to the mechanism postulated in the 1930s. The same cannot be said of the mechanism postulated (Bartlett and Tarbell, 1936) for tribromide ion addition in protic (Dubois and Bienvenue-Goetz, 1968a; Dubois and Huynh, 1971) or in halogenated media (Bellucci et al., 1985b). There are still doubts about the electrophilicity of this species, since the corresponding kinetic term is probably related mainly to a bromide-assisted free bromine addition. Since, from an energetic point of view, free bromine addition can be considered as an ionization process leading from a neutral reagent to a cation-anion pair in a single elementary step, most work on this electrophilic addition can be used to understand how charge separation and stabilization occur in organic reactions. Bromination thus appears as a suitable model, and is complementary to conventional heterolytic substitutions. The data on this latter, however, are frequently less directly related to the ionization step because of complications arising, in particular, from the unresolved question of return (Cox and Maskill, 1983; Paradisi and Bunnett, 1985). In bromination, most of the usual tools of physical organic chemistry (structure-reactivity relationships involving separation of polar, resonance and steric effects, selectivity relationships, substitutes for rate-equilibrium relationships, solvent-reactivity relationships for distinguishing the medium effect and electrophilic and nucleophilic solvent contributions, etc.) have been widely developed in order to interpret kinetic data in terms of transition-state

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structure. In this context, various long-standing concepts regarding the role of substituents and solvent in promoting charge development have been quantitatively evaluated: (a) the relative contributions of conjugated and non-conjugated substituents, entering bromine, anchimerically assisting groups, etc. to the stabilization of cationic transition states and intermediates; (b) the thermodynamic and kinetic contributions to the energy barrier and the magnitude of transition state shifts, in agreement with the Hammond postulate and the Marcus equation; (c) the all-important contributions of the solvents (i) by electrophilic assistance of bromide ion departure and (ii) by nucleophilic solvation in a preassociation mechanism where the nucleophile (which traps the cationic intermediates in the last, product-forming, step) is already involved in the preceding ionization step (Jencks, 1985). The association of kinetics and stereochemistry is particularly useful for obtaining data on the structure, open or bridged depending on the substituents, of bromination intermediates. These short-lived reactive intermediates cannot be observed under the reaction conditions, but indirect kinetic methods enable us to determine the magnitude of bromine bridging on which the selectivity of product formation depends. However, much work has to be done before these intermediates are known well enough for us to understand, and control if possible, the stereo, regio- and chemo-selectivity of the bromination of any olefin. So far, most of the available data concern the two first ionization steps, but the final, product-forming, step is still inaccessible to the usual kinetic techniques. It would therefore be highly interesting to apply to bromination either the method of fast generation of reactive carbocations by pulse radiolysis (McClelland and Steenken, 1988) or the indirect method of competitive trapping (Jencks, 1980) to obtain data on the reactivity and on the life time of bromocation-bromide ion pairs that control this last step and, finally, the selectivities of the bromination products.

Acknowledgements

This work was funded by the Centre National de la Recherche Scientifique (France) and the University of Paris 7. I warmly thank Professeur J. E. Dubois, who initiated most of this work. I am grateful to Dr J. S. Lomas for fruitful discussion. Many thanks are also due to my colleagues, collaborators and students, whose names are cited in the references. I am

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also grateful to Mme B. Dktry and Mr M. Simon for their help in preparing the manuscript.

References Abraham, M. H. and Liszi, J. (1978). J . Chem. SOC., Faraday Trans. I, 1604 Andersen, L., Berg, U. and Petterson, I. (1985). J . Org. Chem. 50, 493 Andrews, L. J. and Keefer, R. M. (1951). J . Am. Chem. SOC.73,462 Andrews, L. J. and Keefer, R. M. (1964). Molecular Complexes in Organic Chemistry. Holden Day, San Francisco Angelini, G. and Speranza, M. (1981). J. Am. SOC. Chem. 103, 3792 Argile, A. and Ruasse, M. F. (1983). J . Org. Chem. 48, 209 Argile, A., Ruasse, M. F and Dubois, J. E. (1984). J . Am. Chem. SOC. 106,4840 Atkinson, J. R. and Bell, R. P. (1963). J . Chem. SOC., 3260 Bach, R. D. and Henneike, H. F. (1970). J. Am. Chem. SOC.92, 5589 Barbier, G. and Dubois, J. E. (1968). J . Chim. Phys. Phys.-Chim. Biol. 65, 1989 Bartlett, P. D. and Tarbell, D. S. (1936). J . Am. Chem. SOC.58, 466 Bellucci, G., Berti, G., Bianchini, R., Ingrosso, G. and Ambrosetti, R. (1980). J . Am. Chem. SOC. 102, 7480 Bellucci, G., Berti, G., Bianchini, R., Ingrosso, G. and Yates, K. (1981). J . Org. Chem. 46, 23 15 Bellucci, G., Bianchini, R. and Ambrosetti, R. (1985a). J . Am. Chem. SOC. 107, 2464 Bellucci, G., Bianchini, R., Ambrosetti, R. and Ingrosso, G. (1985b). J . Org. Chem. 50, 3313 Bellucci, G., Chiappe, C. and Marioni, F. (1987). J . Am. Chem. SOC.109, 515 Bellucci, G., Bianchini, R., Chiappe, C., Marioni, F. and Spagna, R. (1988). J . Am. Chem. SOC. 110, 546 Bellucci, G., Bianchini, R., Chiappe, C., Marioni, F., Ambrosetti, R., Brown, R. S. and Slebocka-Tilk, H. (1989). J . Am. Chem. SOC. 111, 2640 Bellucci, G., Bianchini, R., Chiappe, C. and Marioni, F. ( 1990).J . Org. Chem. 55,4094 Bellucci, G., Chiappe, C., Marioni, F. and Marchetti, F. (1991). J . Phys. Org. Chem. 4, 387 Bentley, T. W. and Carter, G. E. (1982). J . Am. Chem. SOC. 104, 5741 Bentley, T. W. and Llewellyn, G. (1990). Prog. Phys. Org. Chem. 17, 121 Bentley, T. W. and Schleyer, P.v.R. (1976). J . Am. Chem. SOC.98, 7658 Bentley, T W., Bowen, C. T., Morten, D. H. and Schleyer, P.v.R. (1981).J . Am. Chem. SOC. 103, 5466 Bentley, T. W., Carter, G. E. and Roberts, K. (1984). J . Org. Chem. 49, 5183 Bergmann, H. J., Collin, G., Just, G., Miiller-Hagen, G. and Pritzkow, W. (1972). J . Prakt. Chem. 314, 285 Bienvenue-Goetz, E. and Dubois, J. E. (1968). Tetrahedron 24, 6777 Bienvenue-Goetz, E. and Dubois, J. E. (1975). J . Org. Chem. 40, 221 Bienvenue-Goetz, E. and Dubois, J. E. (1978). Tetrahedron 34, 2Q21 Bienvenue-Goetz, E. and Dubois, J. E. (1979). J. Chem. Res. ( S ) 192 Bienvenue-Goetz, E. and Dubois, J. E. (1981). J . Am. Ckem. SOC.103, 5388 Bienvenue-Goetz, E., Dubois, J. E., Pearson, D. W. and Williams, D. L. H. (1970). J . Chem. SOC. ( B ) , 1275

288

M:F.

RUASSE

Bienvenue-Goetz, E., Msika, R. and Dubois, J. E. (1980). J . Chim. Phys. Phys.-Chim. Biol. 77, 803 Bodrikov, I. V., Bronnikova, N. G. and Okrokova, I. S. ( 1973).Zh. Org. Khim. 9,953 Brown, R. S., Gedye, R., Slebocka-Tilk,H., Buschek, J. M. and Kopecki, K. R. (1984). J . Am. Chem. SOC.106, 4515 Brown, R. S., Slebocka-Tilk, H., Bunnett, A. J., Bellucci, G., Bianchini, R. and Ambrosetti, R. (1990). J . Am. Chem. SOC. 112, 6310 Buckles, R. E. and Yuk, J. P. (1953). J . Am. Chem. SOC.75, 5048 Buckles, R. E., Bader, J. M. and Thurmaier, R. J. (1962). J . Org. Chem. 27, 4523 Calvet, A., Josefowicz, M. and Levisalles, J. (1983). Tetrahedron 39, 103 Castaldi, G., Cavicchioli, S., Giordano, C. and Uggeri, F. (1986). Angew. Chem. Int. Ed. Engl. 25, 259 Chang, W. K. and Tidwell, T. T. (1978). J . Org. Chem. 43, 1904 Charton, M. and Charton, B. I. (1973). J . Org. Chem. 38, 1631 Cioslowski,J., Hamilton, T., Scuseria, G., Hess, B. A., Hu, J., Schaad, L. J. and Dupuis, M. (1990). J . Am. Chem. SOC. 112,4183 Collin, G., Jahnke, U., Just, G., Lorenz, G., Pritzkow, W., Rollig, M., Winguth, L., Dietrich, P., Doring, C.-E., Hauthal, H. G. and Wiedenhoft, A. (1969). J . Prakt. Chem. 311, 238 Cox, B. G. and Maskill, H. (1983). J . Chem. SOC.,Perkin Trans. 2, 1901 De la Mare, P. B. D. ( 1976).Electrophilic Halogenation. Cambridge University Press De la Mare, P. B. D. and Bolton, R. (1982). Electrophilic Additions to Unsaturated Systems, 2nd Edn. Elsevier, Oxford Dewar, M. J. S. and Leplay, A. R. (1961). J . Am. Chem. SOC. 83,4560 De Young, S. and Berliner, E. (1977). J . Am. Chem. SOC.99, 290 Dubois, J. E. and Bienvenue-Goetz, E. (1968a). Bull. SOC.Chim. Fr., 2089 Dubois, J. E. and Bienvenue-Goetz, E. (1968b). Bull. SOC. Chim. Fr., 2094 Dubois, J. E. and Chretien, J. R. (1978). J . Am. Chem. SOC. 100, 3506 Dubois, J. E. and Fresnet, P. (1973). Tetrahedron 29, 3407 Dubois, J. E. and Fresnet, P. (1974). Tetrahedron Lett., 2195 Dubois, J. E. and Garnier, F. (1967a). Bull. SOC.Chim. Fr., 4512 Dubois, J. E. and Garnier, F. (1967b). Spectr. Acta 23A, 2279 Dubois, J. E. and Garnier, F. (1968). J . Chem. Soc., Chem. Commun., 241 Dubois, J. E. and Herzog, H. (1963). Bull. SOC.Chim. Fr., 57 Dubois, J. E. and Huynh, X. Q. (1968). Bull. SOC.Chim. Fr., 1436 Dubois, J. E. and Huynh, X. Q. (1971). Tetrahedron Lett., 3369 Dubois, J. E. and LoYzos, M. (1972). C.R. SLances Acad. Sci. SLr. C 274, 1130 Dubois, J. E. and Mouvier, G. (1968). Bull. SOC. Chim. Fr., 1426 Dubois, J. E. and Schwarcz, A. (1964). Tetrahedron Lett., 2167 Dubois, J. E., Alcais, P. and Barbier, G. (1964). J . Electroanal. Chem. 8, 359 Dubois, J. E., Ropars, M. and Fresnet, P. (1965). J . Chim. Phys. 62, 856 Dubois, J. E., Uzan, R. and Alcais, P. (1968). Bull. SOC.Chim. Fr., 617 Dubois, J. E., Hegarty, A. F. and Bergmann, E. D. (1972a). J . Org. Chem. 37, 2218 Dubois, J. E., Aaron, J. J., Alcais, P., Doucet, J. P., Rothenberg, F. and Uzan, R. (1972b). J . Am. Chem. SOC.94, 6823 Dubois, J. E., Kornprobst, J. M. and Meyer, J. J. (1973a). J . Chim. Phys. 70, 1452 Dubois, J. E., Toullec, J. and Fain, D. (1973b). Tetrahedron Lett., 4859 Dubois, J. E., Al-Alaoui, M. and Toullec, J. (1981a). J . Am. Chem. SOC.103, 5393 Dubois, J. E., Lion, C. and Panaye, A. (1981b). Noun J . Chim. 5, 371 Dubois. J. E., Ruasse, M. F. and Poupard, D. (1983). J . Electroanal. Chem. 152, 85

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

289

Durand, J. P., Davidson, M., Hellin, M. and Coussemant, F. (1966). Bull. SOC. Chim. Fr., 43 Fahey, R. C. (1966). J. Am. Chem. SOC.88,4681 Fahey, R. C. and Schneider, H. J. (1968). J . Am. Chem. SOC.90,4429 Fainberg, A. H. and Winstein, S. (1956). J . Am. Chem. SOC. 78, 2770 Freeman, F. (1975). Chem. Rev. 75,439 Fukuzumi, S. and Kochi, J. K. (1981). J . Am. Chem. SOC.103, 2783 Galland, B., Evleth, E. M. and Ruasse, M. F. ( 1990).J . Chem. SOC., Chem. Commun., 898 Gallo, R. (1983). Frog. Phys. Org. Chem. 14, 115 Gamier, F. and Dubois, J. E. (1968). Bull. SOC. Chim. Fr. 3797 Gamier, F., Donnay, R. H. andDubois, J. E.( 1971). J . Chem. SOC.,Chem. Commun., 829 Gebelein, C . G. and Frederick, G. D. (1972). J . Org. Chem. 37, 221 1 Grosjean, D., Mouvier, G. and Dubois, J. E. (1973). Bull. SOC. Chim. Fr., 1735 Grosjean, D., Mouvier, G. and Dubois, J. E. (1976). J . Org. Chem. 41, 3869, 3872 Hamilton, T. P. and Schaefer, H. F. (1990). J . Am. Chem. SOC. 112, 8360 Hamilton, T. P. and Schaefer, H. F. (1991). J . Am. Chem. SOC. 113, 7147 Hancock, C. K., Meyers, E. A. and Yager, B. J. (1961). J . Am. Chem. SOC.83,421 1 Hegarty, A. F., Lomas, J. S., Wright, W. V., Bergmann, E. D. and Dubois, J. E. (1972). J . Org. Chem. 37, 2222 Heublein, G. (1966). J . Prakt. Chem. 303, 84 Ho. T. L. (1977). Hard and Soft Acids and Bases Principle in Organic Chemistry, p. 61. Academic Press, New York Jencks, W. P. (1980). Acc. Chem. Res. 13, 161 Jencks, W. P. (1985). Chem. Reu. 85, 511 Kamlet, M. J.,Abboud, J. L. H. andTaft, R. W.( 1981). Frog. Phys. Org. Chem. 13,485 Kharasch, N. and Orr, W. L. (1956). J . Am. Chem. SOC.78, 1201 Knittel, P. and Tidwell, T. T. (1977). J . Am. Chem. SOC.99, 3408 Kochi, J. K. (1988). Angew. Chem. Int. Ed. Engl. 27, 1227 Koshy, K. M., Roy, D. and Tidwell, T. T. (1979). J . Am. Chem. SOC. 101, 357 Kresge, A. J. and Chen, H. H. (1972). J . Am. Chem. SOC.94, 2818 Langler, R. F. and Tidwell, T. T. (1975). Tetrahedron Lett. 777 Larsen, J. W. and Metzner, A. V. (1972). J . Am. Chem. SOC. 94, 1614 Laurence, C., Guiheneuf, G. and Wojtkowiak, B. ( 1979). J . Am. Chem. SOC.101,4793 Lee, I. (1992). Adv. Phys. Org. Chem. 27, 57 Lenoir, D. (1978). Chem. Ber. 111,411 Loudon, G. M. and Berke, C. (1974). J . Am. Chem. SOC.96,4508 Mayr, H., Will, E., Heigh, V. W. and Shade, C. (1986). Tetrahedron 42,2519 McClelland, R. A. and Steenken, S. (1988). J . Am. Chem. SOC. 110, 5860 Meijer, E. W., Kellog, R. M. and Wynberg, H. (1982). J . Org. Chem. 47, 2005 Mindl, J. and Vecera, M. (1972). Collect. Czech. Chem. Comm. 37, 1143 Modro, A., Schmid, G. H. and Yates, K. (1977). J . Org. Chem. 42, 3673 Modro, A., Schmid, G. H. and Yates, K. (1979). J . Org. Chem. 44,4221 Mouvier, G. and Dubois, J. E. (1968). Bull. SOC. Chim. Fr., 1441 Mouvier, G., Grosjean, D. and Dubois, J. E. (1973). Bull. SOC. Chim. Fr., 1729 Mulliken, R. S. (1952). J . Am. Chem. SOC. 74, 811 Nozaki, K. and Ogg, R. A. (1942). J . Am. Chem. SOC. 64, 697 and 704 Nishida, S. (1967). J . Org. Chem. 32, 2692 Noyce, D. S., Hartter, D. R. and Miles, F. B. (1968). J . Am. Chem. SOC.90, 3794 Okabe, M., Abe, M. and Tada, M. (1982). J . Org. Chem. 47, 1775 Okamoto, Y., Inukai, T. and Brown, H. C. (1958). J . Am. Chem. SOC. 80,4972

290

M.-F. RUASSE

Olah, G. A. (1975). Halonium Ions. Wiley, New York Olah, G. A. and Hockswender, Jr, T. R. (1974). J. Am. Chem. SOC. 96, 3574 Olah, G. A. and White, A. M. (1969). J. Am. Chem. SOC.91, 5801 Olah, G. A., Bollinger, J. M. and Brinich, J. M. (1968). J. Am. Chem. SOC.90, 2587 Olah, G. A., Porter, R. D., Jeuell, C. L. and White, A. M. (1972). J. Am. Chem. SOC. 94, 2044 Olah, G. A., Schilling, P., Westerman, P. W. and Lin, H. C. (1974a). J . Am. Chem. SOC. 96, 3581 Olah, G. A., Westerman, P. W., Melby, E. G. and Mo, Y. K. (1974b). J. Am. Chem. SOC. 96, 3565 Oyama, K. and Tidwell, T. T. (1976). J . Am. Chem. SOC.98,947 Pannel, K. H. and Mayr, A. J. (1982). J. Chem. SOC., Perkin Trans. I , 2153 Paradisi, C. and Bunnett, J. F. (1985). J. Am. Chem. SOC. 107, 8223 Parker, A. J. and Alexander, R. (1968). J. Am. Chem. SOC. 90, 3313 Pincock, J. A. and Yates, K. (1970). Can. J . Chem. 48, 2944 Poirier, R. A,, Mezey, P. G., Yates, K. and Csizmadia, I. G. (1981). J. Mol. Struct. Theochem. 85, 153 Poirier, R. A., Demare, G. R., Yates, K. and Csizmadia, I. G. (1983). J. Mol. Struct. Theochem. 94, 137 Poupard, D., Ruasse, M. F. and Dubois, J. E. (1983). J. Electroanal. Chem. 152, 77 Prisette, J., Seger, G. and Kochanski, E. (1978). J . Am. Chem. SOC. 100, 6941 Raber, D. J., Bingham, R. C., Harris, J. M., Fry, J. L. and Schleyer, P. v. R. (1970). J. Am. Chem. SOC.92, 5977 Raber, D. J., Harris, J. M. and Schleyer, P. v. R. (1974). Ions and Ion Pairs in Organic Chemistry, Vol. 2 (ed. M. Szwarc), p. 247. Wiley, New York Roberts, I. and Kimball, G. E. (1937). J . Am. Chem. SOC.59, 947 Rodriguez, J., Dulctre, J. P. and Bertrand, M. (1984). Tetrahedron Lett., 527 Rolston, J. H. and Yates, K. (1969a). J . Am. Chem. SOC.91, 1483 Rolston, J. H. and Yates, K. (1969b). J . Am. Chem. SOC.91, 1477 Rolston, J. H. and Yates, K. (1969~).J. Am. Chem. SOC.91, 1469 Rothbaum, H. P., Ting, I. and Robertson, P. W. (1948). J . Chem. SOC., 980 Ruasse, M. F. (1985). Isr. J . Chem. 26, 414 Ruasse, M. F. (1988). Actualit6 Chimique, 215 Ruasse, M. F. (1990). Acc. Chem. Res. 23, 87 Ruasse, M. F. and Argile, A. (1983). J. Org. Chem. 48, 202 Ruasse, M. F. and Chretien, J. R. (1993). In preparation Ruasse, M. F. and Dubois, J. E. (1972). J. Org. Chem. 37, 1770 Ruasse, M. F. and Dubois, J. E. (1974). J . Org. Chem. 39, 2441 Ruasse, M. F. and Dubois, J. E. (1975). J. Am. Chem. SOC.97, 1977 Ruasse, M. F. and Dubois, J. E. (1984). J . Am. Chem. SOC. 106, 3230 Ruasse, M. F. and Lefebvre, E. (1984). J. Org. Chem. 49, 3210 Ruasse, M. F. and Motallebi, S. (1988). Bull. SOC.Chim. Fr., 349 Ruasse, M. F. and Motallebi, S. (1991). J. Phys. Org. Chem. 4, 527 Ruasse, M. F. and Zhang, B. L. (1984). J. Org. Chem. 49, 3207 Ruasse, M. F., Argile, A. and Dubois, J. E. (1978). J . Am. Chem. SOC. 100, 7645 Ruasse, M. F., Argile, A., Bienvenue-Goetz, E. and Dubois, J. E. (1979). J . Org. Chem. 44, 2758 Ruasse, M. F., Argile, A. and Dubois, J. E. (1984). J. Am. Chem. SOC. 106,4846 Ruasse, M. F.,Aubard, J., Galland, B. and Adenier, A. (1986).J. Phys. Chem. 90,4382 Ruasse, M. F., Motallebi, S., Galland, B. and Lomas, J. S. (1990).J . Org. Chem. 55,2298

ELECTROPHILIC BROMINATION OF C=C

DOUBLE BONDS

29 1

Ruasse, M. F., Motallebi, S. and Galland, B. (1991). J . Am. Chem. SOC.113, 3440 Schadt, F. L., Bentley, T. W. and Schleyer, P. v. R. ( 1976).J . Am. Chem. SOC.98,7667 Schmid, G. H. (1989). The Chemistry of Double-Bonded Functional Groups, Suppl. A, Vol. 2, Part 1 (ed. S. Patai'), p. 699. Wiley, New York Schmid, G. H. and Garratt, D. G. ( 1977). Chemistry of Alkenes, Vol. 3 (ed. J. Zabicky). Wiley-Interscience, New York Schmid, G. H. and Tidwell, T. T. (1978). J . Org. Chem. 43, 460 Schmid, G. H., Csizmadia, V. M., Nowland, V. J. and Garratt, D. G. (1972). Can. J . Chem. 50, 2457 Schmid, G H., Modro, A. and Yates, K. (1977a). J . Org. Chem. 42, 871 Schmid, G. H., Modro, A. and Yates, K. (1977b). J . Org. Chem. 42, 2021 Sen Sharma, D. K., Meza de Hojer, S. and Kebarle, P. (1985). J . Am. Chem. SOC. 107, 3757 Sergeev, G. B., Serguchev, Yu. A. and Smirnov, V. V. (1973). Russ. Chem. Rev. (Engl. Transl.) 42, 697 Servis, K. L. and Domenick, R. L. (1987). J . Am. Chem. SOC. 107, 7186 Shorter, J. (1972). Advances in Linear Free Energy Relationships (ed. N. B. Chapman and J. Shorter), Chap. 2. Plenum Press, London Shorter, J. ( 1982). Correlation Analysis of Organic Reactivity. Research Studies Press Wiley, New York Slebocka-Tilk, H., Ball, R. G. and Brown, R. S. (1985).J . Am. SOC.Chem. 107,4504 Staley, R. H., Wieting, R.D. and Beauchamp, J. L. ( 1977). J . Am. Chem. SOC.99,5964 Stock, L. M. and Brown, H. C. (1963). Adv. Phys. Org. Chem. 1, 35 Strating, J., Wieringa, J. H. and Wynberg, H. (1969).J.Chem. SOC.,Chem. Commun.,907 Toullec, J. (1979). Tetrahedron Lett., 3089 Ueno, Y., Chino, K., Watanabe, M., Moriya, D. and Okawara, M. (1982).J . Am. Chem. SOC.104, 5564 V'yunov, K. A. and Ginak, A. I. (1981). Russ. Chem. Rev. (Engl. Transl.) 50, 151 Williams, D. L. H., Bienvenue-Goetz, E. and Dubois, J. E. (1969). J . Chem. SOC. ( B ) , 517 Yamabe, S., Minato, T. and Inagaki, S. (1988). J . Chem. SOC.,Chem. Commun., 532 Yates, K. and Leung, H. W. (1980). J . Org. Chem. 45, 1401 Yates, K. and McDonald, R. S. (1973). J . Org. Chem. 38, 2465 Yates, K., McDonald, R. S. and Shapiro, S. A. (1973). J . Org. Chem. 38, 2460 Young, P. R. and Jencks, W. P. (1979). J . Am. Chem. SOC. 101, 3288 Yukawa, Y., Tsuno, Y. and Masawa, M. (1966). Bull. Chem. SOC. Jpn. 39, 2274 Zhang, B. L. (1981). Doctoral thesis, Universite Paris 7