Bromination of toluene

Aqueous dioxan (50%) has been used as a medium for bromination with acidified hypobromous acid and de la Mare and Harvey195 showed that, with perchloric acid as catalyst, the bromination of toluene followed the usual kinetic equation (89). At 25 °C, in ca. 0.0013 M hypobromous acid, the average value of fc2/[H+] for toluene (0.008-0.15 M) was 21.7 and for benzene (0.0011-0.016 M) was 0.60, so that ktoWtnc/kbtaztae was 36.2. The bromination of f-butylbenzene196 and biphenyl197 gave k2/[H+] = 7.25 and 7.52, and hence relative rates of 12.1,... 

Further interpretation of Bruner s results were that the loss of hydrogen bromide from the first formed ArHBr2 complex was proportional to [IBr]3 and the bromination of toluene in carbon tetrachloride at 25 °C was found to give a maximum rate at [I2][Br2] = 0.8, and said to follow the rate equation... 

For instance, bromination of toluene in carbon tetrachloride did not proceed at reflux, even though pentamethylbenzene was brominated at 30°C to give bromopentamethylbenzene quantitatively. Toluene and copper(II) bromide reacted at reflux for 72 h. to give benzyl bromide as the main product. In a similar reaction with alumina-supported copper(II) bromide, bromotoluene (o/p = l) was obtained in good yield and no side-chain-brominated compounds were detected. 

SELECTIVE BROMINATION OF AROMATIC SUBSTRATES Selective Bromination of Toluene... 

Traditional methods for bromination of toluene with bromine and a catalyst result in relatively low / ara-selectivity. For example, bromine in acetic acid gives rise to approximately a 4 1 mixture of the para- and ort/to-bromotoluenes (ref. 4). The para-selectivity is enhanced in trifluoroacetic acid so that approximately 90 % of the para-isomer is produced, but greater selectivity than this is unusual. 

Fig. 5. Bromination of toluene with rerf-butyl hypobromite over various catalysts...

Fig. 6. Effect of diethyl ether on the bromination of toluene Selective Bromination of Naphtalene...

De la Vega and Sasson (ref. 20) added propene oxide as a HBr-scavenger in the bromination of toluene over NaY in CCI4 and obtained an initial p/o-ratio... 

The same principle can be applied to chlorinations and iodinations (ref. 2) as well as to the benzylic bromination of toluenes and related substrates as intermediates to benzaldehydes and benzoic acids (ref. 6). 

Direct bromination of toluene and ethylbenzene form the corresponding benzyl bromides in high yield. The observed selectivity in SC-CO2 is similar to that observed in conventional organic solvents. Also, SC-CO2 is an effective alternative to carbon tetrachloride for use in the classical Ziegler bromination with N-bromosuccinimide. Reaction yields are high, side products are minimized, and bromine-atom selectivities are observed. Thus, SC-CO2 must be useful as a viable, environmentally benign substitute for many of the solvents typically used for free-radical reactions (Tanko and Blackert, 1994). 

Zeolite Beta is also highly effective in the bromination of toluene 255 Reactions of monoalkylbenzenes with bromine in the presence of stoichiometric amounts of zeolite NaY proceed in high yield and with high selectivity to give the corresponding para-bromo products 256... 

Because the rate of substitution varies with position, in a benzene derivative it is more informative and frequently more useful to talk about partial rate factors than about relative rates. A partial rate factor is defined as the rate at one particular position in the benzene derivative relative to the rate of substitution at one position in benzene. Let us, for example, calculate the para and meta partial rate factors (pf and mf, respectively) for bromination of toluene with bromine in aqueous acetic acid. Toluene brominates 605 times faster than benzene under these conditions. The product is 66.8 percent p-, 0.3 percent m-, and 32.9 percent o-bromotoluene. Attack at the para position of toluene occurs 0.668 x 605 times as fast as attack at all six positions of benzene but (0.668 x 605 x 6 = 2420) times as fast as at one position of benzene. Therefore pfCH for bromination of toluene under these conditions is 2420. There are only three times as many total carbons in benzene as meta carbons in toluene. Therefore mfca3 = 0.003 x 605 x 3 = 5.5. The definitions of the partial rate factors for monosubstituted benzenes (—R) are given in Equations 7.78-7.80. 

Bromotoluene has been obtained by the bromination of toluene with bromine in the presence of various catalysts 1 and with hypobromous acid.2 The best method for its preparation, however, is the diazotization of -toluidine followed by replacement of the diazonium group by bromine.3... 

Figure 5.16 Transition states for the bromination of toluene and isopropylbenzene by NBS.

In 1994, the free-radical bromination of toluene (and other alkylaro-matics) in sc C02 was reported (Tanko and Blackert, 1994 Tanko et al., 1994). Product yields were similar to those obtained with conventional solvents. The relative reactivity of the secondary hydrogens of ethylbenzene versus the primary hydrogens of toluene on a per hydrogen basis, r(2°/l°), were assessed via competition experiments and (a) did not vary with pressure, (b) were nearly identical to what is observed in conventional solvents. 

Further, positive reagents are less selective than neutral reagents. The acid-catalyzed bromination of toluene by hypobromous acid is 36.2 more rapid than that of benzene and yields 2.5% ro-bromotoluene... 

Another illustration of the application of the additivity procedure is the scheme employed to determine mp for non-catalytic bromination (Brown and Stock, 1957a). Direct analysis of the products of bromination of toluene indicates only 0.3% m-bromotoluene providing mfe is 5.5 (Table 2). The difficulties in the analysis of the products for the small quantity of meta isomer introduce considerable uncertainty in the partial rate factor. As a test of the observation, the rate of bromination of p-xylene was examined. The additivity treatment (40) yields expression (41),... 

A-l. Write the three most stable resonance contributors to the cyclohexadienyl cation found in the ortho bromination of toluene. 

Free-radical bromination of toluene is selective for the benzylic position. Benzyl bromide cannot undergo elimination, and so nucleophilic substitution of bromide by hydroxide will work well. 

An aromatic compounds containing a substituent can undergo electrophilic substitution at three different positions relative to the substituent. For example in the bromination of toluene (Fig.J), three different products are possible depending on where the bromine enters the ring. These products have the same molecular formula and are therefore constitutional isomers. The aromatic ring is said to be di-substituted and the three possible isomers are referred to as being ortho, meta, and para. The mechanisms leading to these three isomers are shown in Fig. K. 

Out of the three possible isomers arising from thebromination of toluene only two (the ortho and para) are formed in significant quantity. Moreover, the bromination of toluene goes at a faster rate than the bromination of benzene. 

For the synthesis of orfbo-bromotoluene we use a sulphonic acid. o-Bromotoluene could be synthesised by bromination of toluene or by Friedel-Crafts alkylation of bromobenzene (Fig. T). However, the reaction would also give the para substitution product and this is more likely if the electrophile is hindered from approaching the ortho position by unfavourable steric interactions. Alternatively we can substitute a group at the para position before carrying out the bromination. 

Alumina, on the other hand, affects the course of halogenation of anilines and alkenes71,72 and in the presence of sulfuric acid it can even catalyze the chlorination of nitroaromatics73. Bromine supported on alumina serves in the bromination of toluene or... 

Some data on the rate and selectivity in the bromination of toluene in the presence of some Lewis acids and Y zeolites are presented in Table 2. 

TABLE 2. Comparison of Lewis acids and zeolites in catalytic bromination of toluene... 

The rate constant for the bromination of toluene (methylbenzene) is about 4000 times that for benzene (this may sound like a lot, but the fate constant for N,N-dimethylaniline is 1014 times greater). The methyl group also directs electrophiles mostly into the ortho and para positions. These two observations together suggest that alkyl groups may also increase the electron density in the 7t system of the benzene ring, specifically in the ortho and para positions, rather like a weakened version of an OR group. 

The selectivity of free-radical side-chain bromination of toluene derivatives using A-bromosuccinimide and leading to mono- and dibromo-substituted toluenes has been studied in different solvents [577]. Surprisingly, yields and seleetivities are much better in solvents such as methyl formate and dichloromethane than in the more commonly used tetrachloromethane. 

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