The kinetics of the oxidation of 6,7,8-trimethyllumazine, 1, by permanganate in aqueous solution is examined. The pH–rate plot shows a minimum at pH 3.5 and there is catalysis by buffers. Above pH 3.5 the 7-keto compound, 5, is produced by a general base catalyzed route the rate of which is identical to that of the reaction that causes exchange at the 7-methyl group. The kinetic isotope effect for oxidation of the 7-CD3 compound is 6.89 at 31.4°.Below pH 3.5 scission of the pyrazine ring occurs, there is a small isotope effect, and the rate is somewhat faster than that observed for exchange of the 7-methyl group. There appear to be three routes leading to product; one, a permanganate-independent reaction catalyzed by general acids, a second which is also permanganate independent and involves hydration of the substrate, and a third which is permanganate dependent and involves attack by permanganate on the conjugate acid of the substrate.The utility of oxidation as a means of locating hydration sites in heterocyclic compounds is discussed and some comments are made on the mechanism of the enzymic oxidation of the ribityl analog of 1.
