Studies on Fusaric Acid and Analogous Compounds. V

Synthesis of 3-Alkylpicolinic Acids and 5-Methylpicolinic Acid

Abstract

Amination of 3-alkylpyridines with sodium amide in decalin or xylene was not effected except in the case of methyl derivative, which afforded 2-amino-3-methylpyridine. This compound was submitted to consecutive bromination, cyanation, and saponification to prepare 3-methylpicolinic acid. Condensation of 1-acyl-2-iminopropane with 3-ethoxyacrolein diethyl acetal gave 2-methyl-3-acylpyridine, which was reduced by the Wolff-Kishner method, derived to N-oxide, and submitted to the Boekelheide rearrangement. The acetoxymethyl derivatives so obtained were hydrolyzed with hydrochloric acid, and oxidized with activated manganese oxide (Ball reaction). As in the first case mentioned, the 3-alkyl derivatives afforded 3-alkyl-2-pyridinealdehyde in better yield (54.6-62.3%) than that (45%) of non-substituted pyridines. Their mild oxidation gave the objective 3-alkylpicolinic acid with alkyl from methyl to pentyl. 5-Methylpicolinic acid was prepared from 2-methyl-5-ethylpyridine via 2, 5-lutidine but the yield from the Ball reaction was 37.7%, less than that from the 3-alkyl derivatives.