Oxidation of Arylamines

The classical oxidation of the nitrogen atom of arylamines leads to nitro compounds however, hydroxylamines and/or the corresponding azobenzenes can also be obtained. 

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Manno et al. [43] observed the formation of superoxide during the oxidation of arylamines by rat liver microsomes. Noda et al. [44] demonstrated that microsomes are able to oxidize hydrazine into a free radical. In contrast, hepatic cytochrome P-450 apparently oxidizes paracetamol (4 -hydroxyacetanilide) to A-acetyl-p-benzoquinone imine by a two-electron mechanism [45]. Younes [46] proposed that superoxide mediated the microsomal S -oxidation of thiobenzamide. 

However, it was recently reported89 that all nitrosoarenes (except the 4-nitro compound), when produced by the oxidation of arylamines P-H2NC6H4R (R = MeO, Me, Cl, COMe, CONH2, CF3) with 2.2 mol hydrogen peroxide in the presence of a catalytic amount of oxoperoxo(2,6-pyridincdicarboxylato-0,iV,0 ) (hexamethylphosphortriamide)-molybdenum(VII) 171, react with cycohexa-1,3-diene in situ to give the bridged dihy-drooxazines of equation 95 in 66-81% yields. 

Tahled.l Oxidation of arylamines and their derivatives with peroxydisnlfnric acid ... 

Table 4.2 Oxidation of arylamines with peroxycarboxylic acids ...

The oxidation of arylamines with ozone is generally not a feasible route to the corresponding nitro compound. First absorbing the arylamine onto silica gel and then passing a stream of ozone over the surface has achieved some success. m-Chloroperoxybenzoic acid (m-CPBA) in 1,2-dichloroethane at reflux has found limited use. Other more obscure reagents have been... 

Some reagents are milder and less powerful oxidants and have been used to oxidize arylamines to the corresponding nitroso compounds. These include 30 % hydrogen peroxide in acetic acid, ° aqueous solutions of potassium permanganate, and alkaline hypochlorite amongst others. The hypochlorite oxidation of arylamines containing o-nitro substiffients is reported to yield benzofuroxans. For a discussion of the synthesis of aromatic nitroso compounds the readers are directed to a review by Boyer. ... 

The oxidation of arylhydroxylamines and their O-alkylated derivatives to the corresponding nitro compounds can be achieved with both ozone and nitric acid. This strategy is a useful alternative to the oxidation of arylamines. 

Doerge DR, Corbett MD (1991) Peroxygenation mechanism for chloroperoxidase-catalyzed N-oxidation of arylamines. Chem Res Toxicol 4 556-560... 

W. Ando and Y. Moro-oka, Role of Oxygen in Chemistry and Biochemistry , Elsevier, Amsterdam, 1988. Includes chapters on (a) Cation-Radical Chain Catalyzed Oxygenation of Alkenes, by S. F. Nelsen, et al. (b) Photooxygenation of Organic Compounds via Thieir Radical Ions, by K. Mizono and Y. Otsuji (c) Triphenylpyrylium Sensitized Oxygenations, by K. Tokumaru a al. (d) Catalytic Oxidation of Metiiylarenes to Benzaldehydes, by R. A. Shddon and N. de Heij (e) Oxidation of Arylamines with Horseradish Peroxidase, 1 Fujimori et al. (f) Arene Hydroxylation by Cytochrome P-4S0, by M. Tsuda et al., and marry others. 

Uses, (a) Oxidation of arylamines to nitroso compounds. - (b) Baeyer-Villiger oxidation of ketones to lactones (I) - or esters (3). When an aromatic ring is present (2), cleavage occurs adjacent to this ring. ... 

Oxidation of arylamines, nitroso compounds, and azobenzenes. Several 2,6-di-haloanllines have been oxidized successfully to the nitroso compounds with 30% hydrogen peroxide in acetic acid at room temperature. When a solution of the reactants is let stand for a time, crystals of the (dimeric) nitroso compound begin to... 

Oxidations of 2,2 -diaminobiphenyls with sodium perborate, phenyl iodosodiacetate, ° or manganese dioxide have given benzo[c]cinnolines with hydrogen peroxide in acetic acid, cyclization is accompanied by N-oxidation. These reactions, which parallel the oxidation of arylamines... 

Other peroxidases such as HRP or CPO were also able to perform such reactions. Another approach to the production of nitroarenes with peroxidases is based on the CPO (or bromoperoxidase)-catalyzed oxidation of arylamines. Table 16.3-10 gives a selection of peroxidase-catalyzed conversions of aniline derivatives to corresponding nitroarenes. 

The molybdenum-alkyne complex CpMo(CO)3(CCPh) is converted into 1 to exert its catalytic activity during oxidation of arylamines to nitrosoarenes. ... 

Substituted mesoporous silicas are very promising catalysts for the oxidation of arylamines in the liquid phase. Indeed Gontier and Tuel have reported that the performance of TS-1 was considerably poorer than large pore zeolite Ti- and V-substituted molecular sieves for the oxidation of aniline.36 At low oxidant/ aniline ratios it was found that azoxybenzene was the major product using Ti-substituted molecular sieves. In contrast, V-substituted molecular sieves were very selective towards the conversion of aniline to nitrobenzene. The difference between the Ti and V molecular sieves was attributed to the greater number of active oxidising sites in the V-HMS, leading to further oxidation of azoxybenzene into nitrobenzene. 

Nitroso compounds. The oxidation of arylamines to nitroso compounds requires carefully neutralized reagent. Cosolvents (glyme and dioxane) cannot be used. 

H. R. Sonawane, A. V. Pol, P. P. Moghe, S. S. Biswas, A. Sudalai, Selective catalytic oxidation of arylamines to azoxybenzenes with H2O2 over zeolites. Chem. Commun. 1994, 1215-1216. 

A notable exception to the rule of thumb that the nitrosoarene compound is favored under oxidative conditions is the observation of arylhydroxylamine rather than nitrosoarene metabolite in microsomal oxidase studies of arylamine metabolism (43). In vitro studies of N-oxidation generally contain the biological reductant NADPH, which can, by a mechanism independent of cytochrome P-450 catalysis, reduce any nitroso product back to the hydroxylamine state. Our studies on CPX-catalyzed oxidation of arylamines by H2O2 did not require a reductant such as NADPH, and thus, may better reflect the actual enzymatic or equilibrium product of oxidative reactions, including microsomal oxidations. Microsomal oxidations in which substrates such as cumene hydroperoxide are used in place of O2/NADPH should yield the nitrosoarene rather than arylhydroxylamine metabolite. In the case of 4-chloroaniline, the nitroso metabolite rather than the hydroxylamine metabolite was produced however, the major product was the nitroaromatic compound, indicative of further oxidation (55). This raises the hypothetical question as to whether... 

Figure 6. Oxidation of arylamine compounds by the fimgal enzyme chloroperoxidase to form nitrosoarene products.

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