Phenols, benzene-carbon atom reactivity

How does the benzene ring modify the behavior of neighboring reactive centers This chapter takes a closer look at the effects exerted by the ring on the reactivity of alkyl substituents, as well as of attached hydroxy and amino functions. We shall see that the behavior of these groups (introduced in Chapters 3, 8, and 21) is altered by the occurrence of resonance. After considering the special reactivity of aryl-substituted (benzylic) carbon atoms, we turn our attention to the preparation and reactions of phenols and benzenamines (anilines). These compounds are found widely in nature and are used in synthetic procedures as precursors to substances such as aspirin, dyes, and vitamins. 

Upon treatment with HF-SbFj, para-substituted phenols (or their methyl ethers) can be diprotonated [66], first on the oxygen atom and then on the meta carbon [67]. The resulting dipositively charged species are exceedingly reactive towards a variety of arenes [67], 4-Arylcyclohexanones, the primary products of the reactions, can be further transformed to 3-arylcyclohexanones. The ratio of the two isomers depends on conditions such as the reaction time, amount of acid, and the nature of the substrates. For example, when p-cresol is reacted with benzene in the presence of HF-SbFs, 4-methyl-4-phenylcyclohexenone and 3-phenyl-4-methylcyclohexenone are obtained in yields of 29 and 33 %, respectively, after 90 s. By increasing the reaction time to 15 min, the yield of 3-phenyl-4-methylcyclohexenone is increased to 90 % whereas that of 4-methyl-4-phenylcyclohexenone decreased to 2-3 % (Eq. 27). 

Hydroxyl radicals possess week electrophilic properties as indicated by the order of reactivity of substituted benzenes and distribution of phenolic isomers, although the latter depends on the reaction conditions [28, 29]. The Fenton hydroxylation in aqueous solution reveals small (<5%) values of the NIH shift (i.e., migration of hydrogen atom from the site of hydroxylation to the adjacent carbon [30]). The reaction in CH CN demonstrated remarkably high shift values (30-40%) [31], which is typical of enzymatic processes [30]. Sawyer and coworkers proposed that the change in solvent might favor a mechanistic shift from HO to a metal-centered oxidant [32]. 

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