Acid catalysis, general arene oxides

Detailed study of the mechanism of solvolysis of a number of non-K-region arene oxides like 86,90 alkyl substituted benzene oxides,91 45,47,88 and 4888 has been carried out. They present a simple and consistent picture (Fig. 3). Below pH 6 all of them show general acid catalysis, and above pH 6 the rate remains constant with an increase in pH. The pH dependence of aromatiza-tion of 45 is described in terms of two independent reactions taking place... 

At least two systems can be cited as catalysts of peroxide oxidation the first are the iron (III) porphyrins (44) and the second are the Gif reagents (45,46), based on iron salt catalysis in a pyridine/acetic acid solvent with peroxide reagents and other oxidants. The author s opinion is that more than systems for stress testing these are tools useful for the synthesis of impurities, especially epoxides. From another point of view, they are often considered as potential biomimetic systems, predicting drug metabolism. Metabolites are sometimes also degradation impurities, but this is not a general rule, because enzymes and free radicals have different reactivity an example is the metabolic synthesis of arene oxides that never can be obtained by radical oxidation. 

General acid catalysis in the hydrolysis of 81 is quite facile. This reaction, as discussed in Section Benzylic epoxides and arene oxides and shown in Scheme 39, involves proton transfer to the epoxide oxygen concerted with epoxide C-O bond breaking to form a carbocation 83. For primary ammonium ions with pKa < 8, only the acid form of the amine is reactive, and carbocation formation is irreversible,... 

The intermediate is considered to be (303) which either reverts to starting material or yields the o -hydroxy compound (304) by either acid or base catalysis. Rates of reaction are very dependent on positions of the substituents and while the conversion of (305) to (306) is efficient, the corresponding process of (307) proceeds slowly. Introduction of dimethylamino substituents markedly reduces the photoreactivity of the azoxybenzene and products derived from intramolecular hydrogen abstraction and cleavage of N=N or C=N bonds become evident. The conversion of (305) to (307) is reported to be a general one-way process for these systems and the azoxy isomer formed is always that with the N-oxide function far from the arene moiety which has the stronger electron donating substituent. 

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