Aromatics benzylic oxidation

Alkyl groups attached to aromatic rings are oxidized more readily than the ring in alkaline media. Complete oxidation to benzoic acids usually occurs with nonspecific oxidants such as KMnO, but activated tertiary carbon atoms can be oxidized to the corresponding alcohols (R. Stewart, 1965 D. Arndt, 1975). With mercury(ll) acetate, allyiic and benzylic oxidations are aJso possible. It is most widely used in the mild dehydrogenation of tertiary amines to give, enamines or heteroarenes (M. Shamma, 1970 H. Arzoumanian. 1971 A. Friedrich, 1975). 

Oxidation to Quinones. Direct oxidation of arenes to quinones can be accom-plished by a number of reagents. Very little is known, however, about the mechanism of these oxidations. Benzene exhibits very low reactivity, and its alkyl-substituted derivatives undergo benzylic oxidation. Electrochemical methods appear to be promising in the production of p-benzoquinone.797 In contrast, polynuclear aromatic compounds are readily converted to the corresponding quinones. 

Aromatic hydrocarbons are mainly hydroxylated to phenolic products. Complex (12) hydroxylated benzene in MeCN at 20 °C into phenol in ca. 55% yield, and no isotope effect was found for this reaction. Hydroxylation of toluene mainly occurs at the ring positions, with minor amounts of benzylic oxidation products. Hydroxylation of 4-deuterotoluene by (12) occurred with 70% retention and migration of deuterium in the formation of p-cresol. This high NIH shift value is in the same range as that found for liver microsome cytochrome P-450 hydroxylase, and suggests the transient formation of arene oxide intermediates. 

Aromatic, benzylic, and aliphatic thiols 135 are oxidized to the corresponding disulphides 136 by sodium tellurite under phase transfer conditions200 (Scheme 73). 

The oxidation of substituted aromatic hydrocarbons by Mn(OAc)3 in refluxing acetic acid proceeds by two competing mechanisms (a) a free radical addition of carboxymethyl radical to the nuclear ring, forming 2-arylacetic acids and (b) a benzylic hydrogen abstraction by Mn resulting in the formation of benzyl acetates. " In the presence of strong acids such as sulfuric, trichloro- or trifluoro-acetic acids, only benzylic oxidation products are readily formed at room temperature (equation 207). ... 

Benzylic oxidation. By this reagent combination in MeCN, benzyl ethers are oxidized to benzoic esters (11 examples, 81-93%). Arylacetic acids undergo oxidative decarboxylation which results in aromatic aldehydes (10 examples, 52-84%). ... 

Scheme 5.7. Benzylic oxidation to aromatic ketones with sodium bismuthate [98TL7247].

Benzylic oxidation of aromatic side-chains is also a well established technology in the bulk chemicals arena, e. g. toluene to benzoic acid and p-xylene to ter-ephthalic acid [1,2]. These processes involve homogeneous catalysis by, e. g., cobalt compounds, however, and also fall outside the scope of this book. Ammoxi-dation of methyl-substituted aromatic and heteroaromatic compounds is performed over heterogeneous catalysts in the gas phase but this reaction is treated elsewhere (Section 9.5). Transition metal-substituted molecular sieves have been widely studied as heterogeneous catalysts for oxidation of aromatic side-chains in the liquid phase, but there are serious doubts about their heterogeneity [5,6]. Here again, a cursory examination of the literature reveals that supported palladium seems to be the only heterogeneous catalyst with synthetic utility [4]. 

Few investigations have been devoted to the scope of palladium-catalyzed benzylic oxidation. Electron-donating substituents, e.g. MeO, in the aromatic ring have a promoting effect no reaction was observed with /7-nitrotoluene... 

Soluble chromium compounds are known to catalyze the allylic oxidation of olefins [22,23] and benzylic oxidations of alkyl aromatics [22,24] using tert-butyl-hydroperoxide as the primary oxidant. Chromium-substituted aluminophosphates, e. g. CrAPO-5, were shown to catalyze the allylic oxidation of a variety of terpene substrates with TBHP to give the corresponding enones [25,26]. For example, a-pinene afforded verbenone with 77% selectivity (Eq. 6) and 13% of the corresponding alcohol. 

Similarly, the CrAPO-5- and chromium silicalite-1 (CrS-l)-catalyzed oxidation of aromatic side-chains with TBHP or O2 as the primary oxidant [27-31] almost certainly arises as a result of soluble chromium(VI) leached from the catalyst. The same probably applies to benzylic oxidations with TBHP catalyzed by chromium-pillared montmorillonite [32]. More recently, a chromium Schiff s base complex tethered to the mesoporous silica, MCM-41, was claimed [33] to be an active and stable catalyst for the autoxidation of alkylaromatic side-chains. It would seem unlikely, however, that Schiff s base ligands can survive autoxidation conditions. Indeed, on the basis of our experience with chromium-substituted molecular sieves we consider it unlikely that a heterogeneous chromium catalyst can be developed that is both active and stable to leaching under normal oxidizing conditions with O2 or RO2H in the liquid phase. Similarly, vanadium-substituted molecular sieves are also unstable towards leaching under oxidizing conditions in the liquid phase [6,34]. 

Sodium alkoxides can be used with aromatic aldehydes, as was already discovered by Claisen.509 For instance, benzyl benzoate is obtained in 90-93% yield from benzaldehyde in the presence of sodium benzyl oxide.1 510 However, aliphatic aldehydes undergo the aldol condensation under the influence of sodium alkoxides. 

Benzylic Oxidation. During the preparation of 4-ethyl or 4-benzylpyridines via aromatization of dihydropyridine derivatives... 

---