Selective Oxidation of Aromatic Rings

Boreskov Institute of Catalysis, Novosibirsk State University, Novosibirsk, Russia 

While numerous hterature deals with oxygenation of sp C—H bonds, reviews that focus, at least partially, on the oxidation of aromatic sp C—H bonds are scarce [11-14], The aim of this chapter is to give the reader an overview on the current state of the art in the field of the selective aromatic oxidation. The scope of this review is hmited to aromatic C—H bond oxygenation and oxidative dehydrogenation, that is, to the formation of C—O and C=0 bonds with retention of ring C—C 

Arene Chemistry Reaction Mechanisms and Methods for Aromatic Compounds, First Edition. Edited by Jacques Mortier. 

SCHEME 14.1 Aromatic oxidations as key steps in the s3mthesis of bioactive compounds. 

The majority of selective oxidation mechanisms can be divided into two fundamentally different types homolytic and heterolytic ones [15]. Homolytic mechanisms involve one-electron elementary steps, such as hydrogen atom transfer (HAT), single electron transfer (SET), addition of a radical species to aromatic nuclear, etc. Heterolytic mechanisms do not engage radical species and merge a range of two-electron processes, that is, oxygen atom transfer or hydride transfer. In this section, we discuss some fundamental features of the mechanisms relevant for the selective oxidation of aromatic rings. 

---

The selective oxidation of aromatic rings plays a central role in organic synthesis [1, 2] and biological systems [3], Phenols are important antioxidants and intermediates in the production of resins, plastics, fine chemicals, and pharmaceuticals [1, 4]. Quinones serve as versatile building blocks en route to many biologically active compounds [2, 5-7]. Scheme 14.1 presents examples demonstrating utUity of nuclear aromatic oxidation in the production of vital fine chemicals. 

Recently the Co/Mn/N-hydroxyphthalimide (NHPI) systems of Ishii have been added to the list of aerobic oxidations of hydrocarbons, including both aromatic side chains and alkanes. For example, toluene was oxidized to benzoic acid at 25°C [125] and cyclohexane afforded adipic acid in 73% selectivity at 73% conversion [126], see Fig. 4.46. A related system, employing N-hydroxysac-charine, instead of NHPI was reported for the selective oxidation of large ring cycloalkanes [127]. 

Important industrial products are manufactured by direct oxidation of aromatic rings as well as by the selective oxidation of alkyl side chains on aromatic hydrocarbons (Figs. 3 and 4j. 

Selective oxidation of either the aromatic ring or the side chain can also be accompHshed. For example, epoxidation of the double bond of cinnamic acid is effected in excellent yield by treatment with potassium hydrogen persulfate (10). 

The selective oxidation of the activated aromatic ring, substituted with electron-donating hydroxy or methoxy groups, can be perfomed at relatively low electrode potential (Ep = 0.3-1.2 V vs SCE) and ring closure is the result of the intramolecular nucleophilic attack of an amino group on the oxidized aromatic ring. 

The same radical cation is believed to be the intermediate when oxidation of aromatics is carried out with peroxydisulfate739,745 or peroxydiphosphate.746 In the presence of suitable oxidants such as Cu(II), phenolic products are formed with high selectivity. This supports the suggestion that initial attack on the aromatic ring gives rise to 96, which, in turn, reacts rapidly with water to yield the hydroxy-cyclohexadienyl radical ... 

Several procedures for the synthesis of aromatic aldehydes are available which involve the selective oxidation of a methyl group attached to an aromatic ring. A useful general reagent is a solution of chromium trioxide in acetic anhydride and acetic acid. The aldehyde is converted into the gem-diacetate as it is formed and is thus protected from further oxidation. The aldehyde is liberated from the diacetate by hydrolysis under acid conditions the yields, however, are frequently only moderate (e.g. p-nitrobenzaldehyde, Expt 6.117). 

Peroxyacetic acid oxidation is similar to the peroxytrifluoroacetic acid (Deno) oxidation (28). These peroxide systems are reported to selectively oxidize the aromatic portions of molecules while leaving aliphatic portions intact (29). Peroxyacetic acid will oxidize aromatic units to phenolic units via hydroxylation. These phenolic moieties will oxidize rapidly to ortho and para quinones, the latter of which are unstable are undergo ring fission to form diene carboxylic acids (30). 

---