Synthesis of Derivatives of N-Methyl-2-Pyridone from Nicotinic Acid and Nicotinamide

THE OXIDATION OF SOME β-SUBSTITUTED PYRIDINE ALKIODIDES1

“…The present work was then undertaken to determine whether the nature of the 0-substituent would affect the orientation of the chemical oxidation. While our investigation was in progress Wiegand and Holman (4) reported that the low temperature oxidation of nicotinamide methiodide by ferricyanide gave 1-methyl-2-pyridone-3-carboxamide. We therefore extended our investigation to include a study of the apparent discrepancy between the results of Huff and those of Wiegand and Holman.…”

“…VI action could occur easily between the oxygen atoms of the carboxylate ion (formed in basic solution) and the hydrogen atom of the hydroxyl group in the 2-hydroxylated compound, but not, of course, in the pseudo-base with the hydroxyl group at the 6-position. 4 In addition, the ionic charge would tend to block pseudo-base formation at the 2-position because of its electrostatic repulsion on the approaching hydroxide ion. These combined effects are perhaps sufficient to explain the absence of l-methyl-2-pyridone-3-carboxylic acid in the product obtained by chemical oxidation of nicotinic acid methosulfate in basic solution.…”

“…Similarly, an examination of the models of the pseudo-bases of l-methyl-3cyanopyridine hydroxide suggests that the highly negative nitrile nitrogen is favorably situated spatially to interact with the hydrogen of the hydroxyl in the 2-position to decrease its acidity, and thereby to inhibit oxidation at the 2-position and to favor formation of the 2,5-substituted product. 4 The interaction in this case is not classified as hydrogen bonding with chelation because the system of two conjugated double bonds ordinarily considered as required for chelation is lacking. On the basis of these results it is suggested that considerable caution should be exercised in applying the results of purely chemical studies to problems of biochemical reactivity.…”

Niacinamide - Mechanisms of Action and Its Topical Use in Dermatology

“…Today, niacinamide is produced solely synthetically. Three different methods are available: (1) oxidation of 3-ethyl-6-methylpyridine and HNO 3 into nicotinic acid which is then transformed with NH 3 to nicotinic acid amide; (2) aminolysis of methyl nicotinate and gaseous NH 3 , and (3) ammoxidation of 3-methylpyridine into cyanpyridine that is then partially saponified into nicotinamide [4,5,6]. …”

The Biochemical Pathways of Nicotinamide-Derived Pyridones

“…Finally, the N-methyl derivatives of 4PY and 6PY (N-Me-2PY, N-Me-4PY, and N-Me-6PY, respectively) were prepared by methylation with methyl iodide. N-methyl-2-pyridone, N-Me-2PY was obtained by oxidation of N-methyl nicotinamide with K 3 Fe(CN) 6 under basic conditions [33,34]. As described above, N-methyl-nicotinamide oxidizes to three possible forms, N-Me-2PY, N-Me-4PY, and N-Me-6PY.…”