Halogenation of alkyl benzenes

Radical halogenation of alkanes was discussed in Chapter 15. The mechanism of radical halogenation at an allylic carbon was given in Section 15.10. 

We finish Chapter 18 by learning some additional reactions of substituted benzenes that greatly expand the ability to synthesize benzene derivatives. These reactions do not involve the benzene ring itself, so they are not further examples of electrophilic aromatic substitution. In Seaion 18.13 we return to radical halogenation, and in Section 18.14 we examine useful oxidation and reduction reactions. 

Benzylic C - H bonds are weaker than most other sp hybridized C — H bonds, because homolysis forms a resonance-stabilized benzylic radical. 

The bond dissociation energy for a benzylic C-H bond (85 kcal/mol) is even less than the bond dissociation energy for a 3° C-H bond (91 kcal/mol). 

As a result, an alkyl benzene undergoes selective bromination at the weak benzylic C—H bond under radical conditions to form a benzylic halide. For example, radical bromination of ethylbenzene using either Br2 (in the presence of light or heat) or A/-bromosuccinimide (NBS, in the presence of light or peroxides) forms a benzylic bromide as the sole product. 

This pathway does NOT form the desired product. 

Pathway [1] yields both the desired para product as well as the undesired ortho isomer. Because these compounds are constitutional isomers, they are separable. Obtaining such a mixture of ortho and para isomers is often unavoidable. 

The CH3 group in o-nitrotoluene is an ortho, para director and the NO2 group is a meta director. Because the two substituents are ortho to each other, the ortho, para director must be introduced first. The synthesis thus involves two steps Friedel-Crafts alkylation followed by nitration. 

Problem 18.26 Devise a synthesis of each compound from the indicated starting material. 

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Secondary alkyl halides react by a similar mechanism involving attack on benzene by a secondary carbocation Methyl and ethyl halides do not form carbocations when treated with aluminum chloride but do alkylate benzene under Friedel-Crafts conditions The aluminum chloride complexes of methyl and ethyl halides contain highly polarized carbon-halogen bonds and these complexes are the electrophilic species that react with benzene... 

A central core of benzene rings is linked by a fuactioaal group X. The most common end groups at the para sites, and R2, are alkyl (—C H2 ) or alkoxy (—OC H2 + ), or acyl chains C SI NO2 cinnamate (—CH=CHCOOC H2 ) or halogens. Cyclohexane rings can sometimes replace one or more of the benzene rings without loss of Hquid crystallinity. 

Reactions other than those of the nucleophilic reactivity of alkyl sulfates iavolve reactions with hydrocarbons, thermal degradation, sulfonation, halogenation of the alkyl groups, and reduction of the sulfate groups. Aromatic hydrocarbons, eg, benzene and naphthalene, react with alkyl sulfates when cataly2ed by aluminum chloride to give Fhedel-Crafts-type alkylation product mixtures (59). Isobutane is readily alkylated by a dipropyl sulfate mixture from the reaction of propylene ia propane with sulfuric acid (60). 

Secondly, the rates and modes of reaction of the intermediates are dependent on their detailed structure. For example, the stability of the cation radical formed by the oxidation of tertiary aromatic amines is markedly dependent on the type and degree of substitution in the p-position (Adams, 1969b Nelson and Adams, 1968 Seo et al., 1966), and the rate of loss of halogen from the anion radical formed during the reduction of haloalkyl-nitrobenzenes is dependent on the size and position of alkyl substituent and the increase in the rate of this reaction may be correlated with the degree to which the nitro group is twisted out of the plane of the benzene ring (Danen et al., 1969). 

Figure 6.8 Relationship of enthalpy to log k values. Column, ODS silica, ERC-ODS, 15 cm x 6.0 mm i.d. eluent, 80% aqueous acetonitrile at 30 °C. Numbers beside symbols see Table 6.4. O, Polycyclic aromatic hydrocarbons x, alkyl-benzenes, O, halogenated benzenes A, alkanols and , alkanes.

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