Benzene, electrophilic bromination

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. 

Figure 16.3 An energy diagram for the electrophilic bromination of benzene. The overall process is exergonic.

The pKa of p-cyclopropylbenzoic acid is 4.45. Is cvclopropylbenzene likely to be more reactive or less reactive than benzene toward electrophilic bromination Explain. 

Bromination The five-membered aromatic heterocycles are all more reactive toward electrophiles than benzene is, and the reactivity is similar to that of phenol. These compounds undergo electrophilic bromination. However, reaction rates vary considerably, and for pyrrole, furan and thiophene the rates are 5.6 x 10, 1.2 x 10 and 1.00, respectively. While unsubstituted five-membered aromatic heterocycles produce a mixture of bromo-derivatives, e.g. bromothiphenes, substituted heterocycles produce a single product. 

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... 

Strong differences in the reactivity of the aromatic C=C double bond compared to the reactivity of the C=C double bond of olefins are observed olefinic electrophilic additions are faster than aromatic electrophilic substitutions. For instance, the addition of molecular bromine to cyclohexene (in acetic acid) is about 1014 times faster than the formation of bromobenzene from benzene and bromine in acetic acid113,114. Nevertheless, the addition of halogens to olefins parallels the Wheland intermediate formation in the halogenation of aromatic substrates. 

The bromine atom has replaced an atom of hydrogen and so this is a substitution reaction. The reagent is electrophilic bromine and the molecule is aromatic so the reaction is electrophilic aromatic substitution and that is the subject of this chapter. We can compare the bromination of cyclohexene and of benzene directly. 

A pAa of 4.45 indicates that p-cyclopropylbenzoic acid is a weaker acid than benzoic acid. This, in turn, indicates that a cyclopropyl group must be electron-donating. Since electron-donating groups increase reactivity in electrophilic substitution reactions, p-cyclopropylbenzene should be more reactive than benzene toward electrophilic bromination. 

The pK oTp-cychopnif ibenLoic acid is 4.4S. is cyclopropylhonzcne likely to be more re-active or less reactive then benzene toward electrophilic bromination Explain. 

The fused benzene ring in benzimidazole deactivates C-2 to electrophilic bromination by a factor of about 5000. However, most bromination occurs in the fused benzene ring with the preferential order in multiple brominations being 5 > 7 > 6, 4 > 2, an order which closely parallels that predicted by MO calculations. These reactions will be discussed in more detail as substituent reactions (Section 4.07.3.1). 

The difficulty of monobrominating benzimidazole and its 1-substituted derivatives mirrors the state of affairs with the uncondensed imidazoles. Electrophilic bromination occurs at first in the 5-position, then at C-7, but excess brominating agent often substitutes all available positions on the fused benzene ring [23]. It has been found, though, that NBS supported on silica gel forms the 2-bromobenzimidazole (67%) in the first instance [32]. The same compound can also be made from 2-benzimidazolone, and it should be readily available via the 2-anion formed by reaction of an Al-protected benzimidazole with LDA, n-butyllithium or t-butyllithium. Hydroxymethyl and A -(dialkylamino)methyl protecting groups would appear to be the best choices [24, 25]. 

An electrophilic aromatic substitution reaction begins in a similar wav. but there are a number of differences. One difference is that aromatic ring.< are less reactive toward electrophiles than alkenes are. For example, Br in CH2CI2 solution reacts instantly with most alkenes but does not react at room temperature with benzene. For bromination of benzene to take plai a catalyst such as PeBrj is needed. The catalyst makes the Br2 molecu.. more electrophilic by polarizing it to give an FeBr4" Br species that reaci as if it were Br. ... 

This mixing of such levels of property occurs consciously or sub-consciously even amongst teachers and professors. For example, an organic chemist might do the following as he or she explains the mechanism of an electrophilic substitution reaction, the bromination of benzene the bromine approaches the benzene (...) bromine attacks the benzene core (...) the electrons relocate and the bromine splits (...) bromobenzene results (...) a bromine has substituted a hydrogen . 

The reaction of benzene with bromine or chlorine in the presence of a Lewis acid catalyst (such as FeBr3, FeCl3 or A1C13) leads to the formation of bromobenzene or chlorobenzene, respectively. The Lewis acid, which does not have a full outer electron shell, can form a complex with bromine or chlorine. This polarises the halogen-halogen bond (making the halogen more electrophilic), and attack occurs at the positive end of the complex. 

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