Bromination of benzene

Step 2 Electrophilic attack and fcamation of the sigma complex. H 

Comparison with Alkenes Benzene is not as reactive as alkenes, which react rapidly with bromine at room temperature to give addition products (Section 8-8). For example, cyclohexene reacts to give rrans-l,2-dibromocyclohexane. This reaction is exothermic by about 121 kJ/mol (29 kcal/mol). 

The analogous addition of bromine to benzene is endothermic because it requires the loss of aromatic stability. The addition is not seen under normal circumstances. 

The energy diagram for the bromination of benzene shows that the first step is endothermic and rate-limiting and the second step is strongly exothermic. 

The substitution of bromine for a hydrogen atom gives an aromatic product. The substitution is exothermic, but it requires a Lewis acid catalyst to convert bromine to a stronger electrophile. 

Step 1 The bromine-iron(III) bromide complex is the active electrophile that reacts with benzene. Two of the tt electrons of benzene are used to form a bond to bromine and give a cyclohexadienyl cation intermediate. (The molecular model depicts the cyclohexadienyl cation intermediate.) 

Step 2 Loss of a proton from the cyclohexadienyl cation yields bromobenzene. 

The formation of a reactive halogenating species through oxidation occurs in biosynthetic halogenation, described in the Boxed Essay. Syntheses of aryl fluorides and aryl iodides 

6-Dichloro-3,5-dimethoxytoluene an antifungal compound isolated from lily plants 

Dibromoindigo principal constituent of a dye known as Tyrian purple and prized by ancient cultures, isolated from a species of Mediterranean sea snail 

Complexation of bromine with iron(III) bromide makes bromine more electrophilic, and it reacts with benzene to give a cyclohexadienyl intermediate as shown in step 1 of Mechanism 12.3. In step 2, as in nitration and sulfonation, loss of a proton from the cyclohexadienyl cation is rapid and gives the product of electrophilic aromatic substitution. 

Only small quantities of iron(III) bromide are required. It is a catalyst for the bromination and, as Mechanism 12.3 indicates, is regenerated in the course of the reaction. WeTl see later in this chapter that some aromatic substrates are much more reactive than benzene and react rapidly with bromine even in the absence of a catalyst. 

Chlorination is carried out in a manner similar to bromination and follows an anala-gous mechanism to give aryl chlorides. 

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The halogen carriers or aromatic halogenation catalysts are usually all electrophilic reagents (ferric and aluminium haUdes, etc.) and their function appears to be to increase the electrophilic activity of the halogen. Thus the mechanism for the bromination of benzene in the presence of iron can be repre-sfflited by the following scheme ... 

The heats of formation of Tt-complexes are small thus, — A//2soc for complexes of benzene and mesitylene with iodine in carbon tetrachloride are 5-5 and i2-o kj mol , respectively. Although substituent effects which increase the rates of electrophilic substitutions also increase the stabilities of the 7r-complexes, these effects are very much weaker in the latter circumstances than in the former the heats of formation just quoted should be compared with the relative rates of chlorination and bromination of benzene and mesitylene (i 3 o6 x 10 and i a-Sq x 10 , respectively, in acetic acid at 25 °C). 

Molecular bromine is believed to be the reactive brominating agent in uncatalyzed brominations. The brominations of benzene and toluene are first-order in both bromine and the aromatic substrate in trifluoroacetic acid solution, but the rate expressions become more complicated when these reactions take place in the presence of water. " The bromination of benzene in aqueous acetic acid exhibits a first-order dependence on bromine concentration when bromide ion is present. The observed rate is dependent on bromide ion concentration, decreasing with increasing bromide ion concentration. The detailed kinetics are consistent with a rate-determining formation of the n-complex when bromide ion concentration is low, but with a shift to reversible formation of the n-complex... 

Bromination is catalyzed by Lewis acids, and a study of the kinetics of bromination of benzene and toluene in the presence of aluminum chloride has been reported. Toluene is found to be about 35 times more reactive than benzene under these conditions. The catalyzed reaction thus shows a good deal less substrate selectivity than the uncatalyzed reaction, as would be expected on the basis of the greater reactivity of the aluminum chloride-bromine complex. 

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.

De la Mare and Hilton198 measured the rates at 25 °C of bromination of benzene, benzoic acid, phthalic acid, 2-nitrobenzoic acid, trimethylanilinium perchlorate and nitrobenzene by hypobromous acid with sulphuric or perchloric acids as catalysts, in some cases in aqueous dioxan, in an attempt to discover if Br+ or H2OBr+ was the appropriate brominating species since the logarithm of the rates should then follow the acidity functions H0 or HR (J0) respectively. The results, however, were inconclusive and relative rates of bromination were determined (see Table 53). 

More recently, the kinetics of bromination of benzene in water have been examined296. The reaction is second-order overall and the slope of the plot kobs... 

Subsequently, rate coefficients were determined for the zinc chloride-catalysed bromination of benzene, toluene, i-propyl-benzene, r-butylbenzene, xylenes, p-di-f-butylbenzene, mesitylene, 1,2,4-trimethyl-, sym-triethyl-, sym-tri-f-butyl-, 1,2,3,5-and 1,2,4,5-tetramethyl- and pentamethylbenzenes, all at 25.4 °C and in acetic acid, and it was shown that the reaction was inhibited by HBr.ZnCl2 which accumulates during the bromination and was considered to cause the first step of the reaction (formation of ArHBr2) to reverse320. The second-order coefficients for bromination of o-xylene at 25.0 °C were shown to be inversely dependent upon the hydrogen bromide concentration and the reversal of equilibrium (155)... 

An investigation of the relative rates of bromination of benzene, toluene, m-and p-xylene by bromine in acetic acid, catalysed by mercuric acetate, revealed relative rates almost identical with those obtained with molecular bromine322, though as in the bromination of biphenyl by bromine acetate (p. 129) it is quite inconsistent for a much more reactive electrophile to have the same selectivity. Relative rates were (molecular bromination values in parenthesis) benzene 1.0 toluene, 480 (610) p-xylene, 2.1 x 103 (2.2 x 103) m-xylene 2.0 x 10s (2.1 x 10s). 

Finally, peroxyacetic acid had been used as a catalyst in the bromination of benzene in acetic acid at 60 °C324. The rate of consumption of peroxyacid appeared to be independent of the concentration of benzene and the kinetics followed equation (157), viz. 

This is not unreasonable since it was found that the second-order rate coefficient for bromination of benzene by bromine acetate at 60 °C was 3.20 xlO-2, i.e. twenty times faster than under the above conditions for which 103k2 ranged from ... 

The bromination of benzene illustrates the difference between addition to alkenes and substitution of arenes. First, to achieve the bromination of benzene it is necessary to use a catalyst, such as iron(III) bromide. The catalyst acts as a Lewis acid, binding to the bromine molecule (a Lewis base) and ensuring that the outer bromine atom has a pronounced partial positive charge ... 

An important use of the dediazoniation reaction is to remove an amino group after it has been used to direct one or more other groups to ortho and para positions. For example, the compound 1,3,5-tribromobenzene cannot be prepared by direct bromination of benzene because the bromo group is ortho-para directing however, this compound is easily prepared by the following sequence ... 

Enough mutual polarisation can apparently result, in (8), for (9) to form, but polarisation of the bromine molecule may be greatly increased by the addition of Lewis acids, e.g. AlBr3 (cf. bromination of benzene, p. 138), with consequent rise in the rate of reaction. Formation of (9) usually appears to be the rate-limiting step of the reaction. 

Lewis acids such as FeCl3 and ZnCl2 are also useful catalysts. For example, bromination of benzene by Br2 in the presence of FeBr3 can be shown as... 

Also, ferric ion promotes nuclear (ionic) bromination of benzene derivatives at the expense of the radical reaction at the side chain. 

Bromination of benzene follows the same general mechanism of the electrophilic aromatic substitution. The bromine molecule reacts with FeBr3 by donating a pair of its electrons to it, which creates a more polar Br—Br bond. 

Two excellent reviews <71AHC(13)235, 72IJS(C)(7)6l) have dealt with quantitative aspects of electrophilic substitution on thiophenes. Electrophilic substitution in the thiophene ring appears to proceed in most cases by a mechanism similar to that for the homocyclic benzene substrates. The first step involves the formation of a cr-complex, which is rate determining in most reactions in a few cases the decomposition of this intermediate may be rate determining. Evidence for the similarity of mechanism in the thiophene and benzene series stems from detailed kinetic studies. Thus in protodetritiation of thiophene derivatives in aqueous sulfuric and perchloric acids, a linear correlation between log k and —Ho has been established the slopes are very close to those reported for hydrogen exchanges in benzene derivatives. Likewise, the kinetic profile of the reaction of thiophene derivatives with bromine in acetic acid in the dark is the same as for bromination of benzene derivatives. The activation enthalpies and entropies for bromination of thiophene and mesitylene are very similar. 

The second point is somewhat less obvious but is readily illustrated by the synthesis of 1,3,5-tribromobenzene. This particular substitution pattern cannot be obtained by direct bromination of benzene because bromine is an ortho, para director. Instead, advantage is taken of the powerful activating and ortho, para-directing effects of the amino group in aniline. Bromination of aniline yields 2,4,6-tribromoanihne in quantitative yield. Diazotization of the resulting 2,4,6-tribromoaniline and reduction of the diazonium salt gives the desired 1,3,5-tribromobenzene. 

Exercise 22-9 Devise an experimental test to determine whether the following addition-elimination mechanism for bromination of benzene actually takes place. 

Exercise 22-14 Aluminum chloride is a much more powerful catalyst than ferric bromide for bromination of benzene. Would you expect the combination of aluminum chloride and bromine to give much chlorobenzene in reaction with benzene Explain. 

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