Para-Bromotoluene

When para-bromotoluene is treated with sodium amide, two products are obtained. Draw both products, and propose a plausible mechanism for their formation. 

The hydrolysis of p bromotoluene with aqueous sodium hydroxide at 300°C yields m methylphenol and p methylphenol in a 5 4 ratio What is the meta—para ratio for the same reac tion carried out on p chlorotoluene" ... 

The substitution reaction of toluene with Br2 can, in principle, lead to the formation of three isomeric bromotoluene products. In practice, however, only o- and jp-bromotoluene are formed in substantial amounts. The meta isomer is not formed. Draw the structures of the three possible carbocation intermediates (Problem 15.48), and explain why ortho and para products predominate over meta. 

Next ask yourself, "What is an immediate precursor of p-bromotoluene " Perhaps toluene is an immediate precursor because the methyl group would direct bromination to the ortho and para positions. Alternatively, bromobenzene might be an immediate precursor because we could carry out a Friedel-Cralts methylation and obtain a mixture of ortho and para products. Both answers are satisfactory, although both would also lead unavoidably to a product mixture that would have to be separated. 

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. 

It was of interest to see if the use of tm-butyl hypobromite would provide similar opportunities for regioselectivity to those found in the case of chlorination reactions with te/t-butyl hypochlorite. The initial indications were favourable use of H zeolite X as catalyst in dichloromethane solution gave an almost quantitative yield of bromotoluenes with a para ortho ratio of 81 19 (Fig. 5) (ref. 10). 

Despite the fact that aryl bromides are generally less reactive, o- and p-bromotoluenes could be efficiently vinylated with ethene in DMF/H2O with [Pd(OAc)2] + P(o-tolyl)3 as catalyst and Et3N as base [16]. With careful choice of reaction parameters (90 °C and 6 bar of ethene) all bromotoluene was converted to high purity ortho- or para-vinyltoluene. Under the conditions used, the reaction mixture forms two phases. In this case the main role of water is probably the dissolution of triethylamine hydrobromide which otherwise precipitates from a purely organic reaction medium and causes mechanical problems with stirring. 

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. 

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. 

One of the characteristics of reactions involving benzyne intermediates is that the nucleophile can bond to the same carbon to which the leaving group was bonded, or it can bond to the carbon adjacent to the one to which the leaving group was bonded. This often results in the formation of isomeric products when substituted aromatic halides are used. For example, the reaction of yo-bromotoluene with sodium dimethyl-amide in dimethylamine as the solvent gives a 50 50 mixture of the meta and para... 

Even more striking is the regioselective transformation of the highly structured toluene n-complex, with bromine situated specifically over the ortho and para positions to afford the same isomeric (product) mixture of o- and p-bromotoluenes as that obtained in solution [63]. As close as these pre-equilibrium intermediates are structurally akin to the (ordered) transition states for electrophilic bromination, it is important to emphasize that they are formed essentially upon bimolecular collision with no activation energy, and the donor/acceptor binding is in accord with the Mulliken formulation. 

The methyl hydrogens of toluene are relatively inert to the attack of these charged particles. In contrast, the polarizable 7t-electron system of the aromatic nucleus can be easily perturbed by the approach of the bromine cation. In a simplified form, their interaction can be described in the sequence of the following steps. The attacking cation pulls an electron pair of the aromatic system towards itself to form a C-Br bond. A concerted shift of the next electron pair leads to the development of a positive charge on the methylbearing para-carbon atom. Loss of a proton from this c-complex 13 leads to the formation of bromotoluene with restoration of the aromaticity in the system. Besides the para isomer of bromotoluene 8, the corresponding ortho isomer is also formed, but in lesser amounts. 

The preparation of aryl halides from diazonium salts is more important than direct halogenation for several reasons. First of all, fluorides and iodides, which can seldom be prepared by direct halogenation, can be obtained from the diazonium salts. Second, where direct halogenation yields a mixture of ortho and para isomers, the ortho isomer, at least, is difficult to obtain pure. On the other hand, the ortho and para isomers of the corresponding nitro compounds, from which the diazonium salts ultimately come, can often be separated by fractional distillation (Sec. 11.7). For example, the o- and />bromotoluenes boil only three degrees apart 182° and 185°. The corresponding o- and -nitrotoluenes, however, boil sixteen degrees apart 222° and 238°. 

Ask yourself, What is an immediate precursor of p-bromobenzoic acii There are two substituents on the ring, a carboxyl group (COOH), which i> meta-directing, and a bromine, which is ortho- emd para-directing. We ca brominate benzoic add, because the wrong isomer (m-bromobenzoic aci.. would be produced. We know, however, that oxidation of an alkylbenzcne yields a benzoic add. Thus, an immediate precursor of our target molecule m ht be p-bromotoluene. 

---