Preparation of 2- and 6-pyridones of N’-methylnicotinamide”

In the course of experiments designed to elucidate the structure of reduced diphosphopyridine nucleotide (DPNH) (12), it became necessary to prepare the 2and 6-pyridones of iV-methylnicotinamidel by oxidation of the latter. Huff (5) has described the preparation of N’-methyl-6-pyridone-3-carboxylic acid by alkaline ferricyanide oxidation of either trigonelline or N’-methylnicotinamide. The acid derivative could then be converted to the amide derivative by reaction with thionyl chloride and ammonia. Knox and Grossman (8,9) subsequently reported a direct preparation of the 6-pyridone of N’-methylnicotinamide by enzymatic oxidation of the latter. On this basis they concluded (10) that the 6 carbon of the quaternary nicotinamide structure was the reactive carbon, and as such would be the position involved not only in the oxidation, but also in the reduction of N1-methylnicotinamide. They suggested, therefore, that dihydro-N1-methylnicotinamide, the compound originally studied by Karrer and collaborators (7) as a model of the DPNH structure, and more recently crystallized by Karrer and Blumer (6), was the 1 ,6-dihydro derivative. However, shortly after this suggestion by Knox and Grossman, Holman and Wiegand (4) reported the isolation of only the 2-pyridone of Nl-methylnicotinamide from the alkaline ferricyanide oxidation of Nr-methylnicotinamide. The latter authors, in order to account for their apparent disagreement with the results of Huff, proposed that, under the experimental conditions employed by Huff, some hydrolysis of the amide group