Doebner's Reaction with 6-Methyl-2-amino Pyridine

Abstract

DOEBNER'S reaction has been known since 1887 (ref. 1); it consists of the synthesis of quinoline-4-carboxylic acids, the starting materials being an aromatic amine, an aldehyde and pyruvic acid. It was thought that the reaction with 2-amino pyridine would lead to the formation of 1,8-naphthyridine-4-carboxylic acids², but this was later found to be incorrect. The work of Allen et al. has established that 2-amino pyridine, benzaldehyde and pyruvic acid form a condensation product without cyclization to 1,8-naphthyridine-4-carboxylic acid³. The product was identified as γ-pyridyl-amino-γ-phenyl-α-oxo-butyric acid. The result of the present investigation of Doebner's reaction using 6-methyl-2-amino pyridine agrees with that of Allen et al. It was found that 6-methyl-2-amino pyridine reacts with an aldehyde and pyruvic acids according to the scheme proposed by Allen et al.³. In one representative experiment, 5.4 g (0.05 mole) of 6-methyl-2-amino pyridine was dissolved in 75 ml. of ethyl alcohol in a round bottom flask with three necks equipped with a condenser, a mechanical stirrer and a separatory funnel. The mixture was warmed until all the pyridine went into solution. 7.6 g (0.05 mole) of vanillin was then added and heating was continued. The solution became yellow immediately. At the same time, 4.4 g (0.05 mole) of freshly distilled pyruvic acid was added dropwise through the separatory funnel over a period of 15 min. The mixture was further refluxed for 10 min.