Synthesis and hydrazinolysis of β-(1,3,4-oxadiazol-2-yl)pyridines

Abstract

Keywords: hydrazide, hydrazine, nicotinic acid, 1,3,4-oxadiazole, aromatic acid chlorides.Derivatives of 1,3,4-oxadiazoles have found use as antimicrobial [1,2], antifungal [3,4], antibacterial [5], and sedative preparations [6]. Preparation of 1,3,4-oxadiazoles containing pyridine units is coupled with a number of difficulties, linked with their chemical instability and the complexity of isolating them from the reaction media [7].Previously [8] we studied the reactivity of hydrazides of 3,5-pyridinedicarboxylic acid 1, 2 in acylation reaction with aromatic acids chlorides which proceeded with formation of the hydrochlorides of the corresponding mono-and bis-1,2-diacylhydrazine-2,6-dimethylpyridines 3, 4b-d, g, isolated in the form of the bases.With the objective of preparing the (1,3,4-oxadiazol-2-yl)pyridines 5 and 6 we have investigated the reaction of the heterocycles 3 and 4 with various dehydrating agents (phosphorus oxychloride, thionyl chloride, oleum, and polyphosphoric acid). The most effective cyclizing agent is phosphorus oxychloride. The use of conc. H 2 SO 4 or oleum was ineffective since the reaction did not occur at low temperatures and strong resinification was observed on heating the reaction mixture. Analogous results were obtained when polyphosphoric acid or thionyl chloride were used.Attempts to obtain the (1,3,4-oxadiazol-2-yl)pyridines 5b-d,g,i by heating the 1,2-diacylhydrazines 3b-d, g,i in POCl 3 proceeded in low yield, since, because of the poor solubility of the bases, prolonged heating was required which lead to resinification.