Bromine electrophilic addition

Systematic studies of the selectivity of electrophilic bromine addition to ethylenic bonds are almost inexistent whereas the selectivity of electrophilic bromination of aromatic compounds has been extensively investigated (ref. 1). This surprising difference arises probably from particular features of their reaction mechanisms. Aromatic substitution exhibits only regioselectivity, which is determined by the bromine attack itself, i.e. the selectivity- and rate-determining steps are identical. 

The pn- 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). 

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 /f-bromocarbocations [28]. 

Table 5-23. Stereoselectivity of electrophilic bromine addition to cis- and tranr-stilbene, carried out at 0 °C in the dark [79, 386] cf. Eqs. (5-29) and (5-140).

In addition to polarity and nucleophilicity toward the bromonium ion, other solvent properties may come into play. The rate-limiting step in electrophilic bromine addition is thought to be the conversion of a CT complex to a cation-bromide ion pair, which is consistent with the observation that the rate constant for bromine addition increases as solvent polarity increases. Solvent may also electrophilically assist the removal of the bromide ion from the alkene-Br2 CT complex by hydrogen bonding to a developing bromide ion (Figure 9.6). It has been estimated that this electrophilic solvent participation can lower the energy of bromonium ion formation by 60 kcal/mol. ° Additional support for the role of electrophilic... 

The first step in electrophilic bromination of benzene involves addition of Br, leading to an intermediate bromobenzenium ion. This is then rapidly followed by loss of a proton to give bromobenzene. 

Bromination of 136 in methanol gave the 3-bromo derivative, identical with the product of Sandmeyer reaction of the 3-diazonium salt. When the reactive 3-position was blocked, electrophilic bromination would not take place (66JOC265). Chlorination appears to occur by addition [83AHC(34)79], and perhalides are known [84MI25 90AHC(47)1]. Activating substituents are able to induce some bromination in the pyridine ring. 

Previously published methods for electrophilic bromination of isoquinoline"" lead to mixtures of isomers only separable with difficulty, use expensive additives or large excesses of reactants, or involve multistep procedures. 

Our recent studies on effective bromination and oxidation using benzyltrimethylammonium tribromide (BTMA Br3), stable solid, are described. Those involve electrophilic bromination of aromatic compounds such as phenols, aromatic amines, aromatic ethers, acetanilides, arenes, and thiophene, a-bromination of arenes and acetophenones, and also bromo-addition to alkenes by the use of BTMA Br3. Furthermore, oxidation of alcohols, ethers, 1,4-benzenediols, hindered phenols, primary amines, hydrazo compounds, sulfides, and thiols, haloform reaction of methylketones, N-bromination of amides, Hofmann degradation of amides, and preparation of acylureas and carbamates by the use of BTMA Br3 are also presented. 

Recent studies by Pincock and Yates (32, 33) have demonstrated the intermediacy of vinyl cations in the electrophilic bromination of arylmethyl-acetylenes in acetic acid. The rates of addition of Brj to a number of substituted phenylmethylacetylenes in acetic acid follow the general equation... 

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 every chemical textbook. It is still nowadays presented as a simple two-step, trans-addition involving the famous bromonium ion as the key intermediate. T]nis mechanism was postulated as early as the 1930s by Bartlett and Tarbell (1936) from the kinetics of bromination of trans-stilbene in methanol and by Roberts and Kimball (1937) from stereochemical results on cis- and trans-2-butene bromination. According to their scheme (Scheme 1), bromo-derivatives useful as intermediates in organic synthesis... 

Free halogens are generally inconvenient to use, owing to their toxic and corrosive nature, but can be replaced by quaternary ammonium polyhalides. Quaternary ammonium tribromides are well established [e.g. 1] as solid, readily handled and relatively non-toxic alternatives for electrophilic bromine. More recently, other quaternary ammonium polyhalides have been produced, which together with the tribromides, have wide application as catalysts or in stoichiometric quantities in electrophilic substitution and addition reactions, oxidations, etc. 

To account for the stereospecificity of bromine addition to alkenes, it has been suggested that in the initial electrophilic attack of bromine a cyclic intermediate is formed that has bromine bonded to both carbons of the double bond. Such a bridged ion is called a bromonium ion because the bromine formally carries the positive charge ... 

Another piece of evidence for the bromonium ion is that addition is less regiospecific when bromine is the electrophile then when HaO+ attacks. With molecular bromine we cannot, of course, observe the site at which the original electrophilic bromine attacks, but with unsymmetrical reactants such as HOBr or BrCl we can. Thus, for example, the addition of BrCl to propene in aqueous HC1 gives only 54 percent of the Markownikoff addition product (26) and 46 percent of the anti-Markownikoff product (27). 40 The chloride ion apparently has the... 

Table 9.12 compares partial rate factors for substitution by phenyl radical with those for electrophilic bromination. Selectivity is clearly much lower for the radical substitution furthermore, for attacking phenyl radical, nearly all positions in the substituted benzenes are more reactive than in benzene itself, a finding that reflects the tendency for most substituents to stabilize a radical, and thus to lower transition state energy for formation of the cyclohexadienyl intermediate, when compared with hydrogen. The strong polar effects, which cause the familiar pattern of activation and deactivation in the electrophilic substitutions, are absent. One factor that presumably contributes to the low selectivity in radical attack is an early transition state in the addition step, which is exothermic by roughly 20 kcal mole-1.178... 

Electrophilic addition of the halogens and related X—Y reagents to alkenes and alkynes has been a standard procedure since the beginning of modem organic chemistry.1 Anti electrophilic bromination of such simple compounds as cyclohexene and ( )- and (Z)-2-butene, and variants of this reaction when water or methanol are solvents (formation of halohydrin or their methyl ethers, respectively), are frequently employed as prototype examples of stereospecific reactions in elementary courses in organic chemistry. A simple test for unsaturation involves addition of a dilute solution of bromine in CCU to the... 

In a final ingenious set of experiments, it was shown35 that addition of tri-methyltin bromide resulted in an increase in the values of but in a marked decrease in the values of "bs (see Table 23). These results are explicable if a complex Me3SnBrBr2 is formed (again in but low concentration), since such a complex would be expected to provide a very active source of electrophilic bromine in the second-order mechanism, through a transition state such as (XV). 

Notwithstanding the fact that certain four-center additions to alkenes, e.g. equation (94) or Fig. 22, are forbidden, bromine addition to an alkene does occur. The orbital symmetry arguments which forbid cis addition to isolated bonds favor trans addition in equation (144), in which j = 4, X may be a nucleophile or radical and Y an electrophile or radical. Therefore, additions of molecular bromine or in general X—Y to alkenes, should proceed in at least two steps. Otherwise, separated X and Y, with one electron pair between them, add in concerted fashion to the alkene. Equation (144) is effectively the prototype of numerous ionic and radical a-w exchange reactions. A wealth of information has been recorded in excellent reviews covering special aspects of this general process, e.g. electrophilic additions (de la Mare and Bolton,... 

Aromatic bromination.1 BrF readily undergoes both ionic and radical reactions with arenes, but addition of C2H5OH suppresses radical reaction and permits electrophilic bromination. Simple arenes give mono- and dibromo derivatives. BrF is more useful for bromination of deactivated arenes as shown. 

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