Electrophilic aromatic acetoxylation

The same workers590,591 also showed that, in the Pd(II)-catalyzed acetoxylation of substituted arenes, a complete reversal of the usual pattern of isomer distribution for electrophilic aromatic substitution or anodic oxidation of aromatics is observed. To explain these results it was suggested that acetoxylation by Pd(OAc)2 takes place via the following addition-elimination sequence ... 

The isomer distribution for anodic acetoxylation of a number of monosubstituted benzenes has been determined [122]. The reaction closely resembles ordinary electrophilic aromatic substitution processes, perhaps on the side of low-selectivity reactions. The isotope effect, A h//cd, for nuclear acetoxylation in anisole was found to be 1.0, whereas for a-substitution in ethylbenzene a value of 2.6 was observed. The interpretation of these values is not straightforward [126]. 

If acetoxylation were a conventional electrophilic substitution it is hard to understand why it is not more generally observed in nitration in acetic anhydride. The acetoxylating species is supposed to be very much more selective than the nitrating species, and therefore compared with the situation in (say) toluene in which the ratio of acetoxylation to nitration is small, the introduction of activating substituents into the aromatic nucleus should lead to an increase in the importance of acetoxylation relative to nitration. This is, in fact, observed in the limited range of the alkylbenzenes, although the apparently severe steric requirement of the acetoxylation species is a complicating feature. The failure to observe acetoxylation in the reactions of compounds more reactive than 2-xylene has been attributed to the incursion of another mechan-104... 

Aromatic compounds can be hydroxylated, benzoxylated and acetoxylated and the isomer distributions and substituent effects indicate that the reaction is an electrophilic substitution132. Very little kinetic work has been carried out so that the nature of the electrophile is in some doubt. 

Acetoxylation is found to accompany nitration of fairly reactive aromatics by nitric acid in acetic anhydride and gives rise to zeroth-order kinetics76. The electrophile is believed to be protonated acetyl nitrate the formation of which is rate-determining, hence the kinetic order (see p. 37). Acetoxylation can also accompany halogenation by positive halogenating agents in acetic acid solvent, especially in the presence of sodium acetate137, but no kinetic studies have been carried out. 

Nitration is widely applicable, can be carried out under a variety of conditions, can usually be stopped cleanly after mononitration, is usually effected by the nitronium ion, can take place on a neutral molecule or a cation, and in many cases can be considered as the standard aromatic electrophilic substitution. However, this last point must be treated with caution. Depending on the reaction conditions and reagents, the mechanism of the reaction does vary, and accompanying reactions such as oxidation (due to the oxidative action of nitric acid), acetoxylation (by acetyl nitrate), and migration of nitro groups following ipso attack (80MI1) can occur. Ipso nitration processes have been extensively studied by Fischer and co-workers. 

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