Studies on the synthesis of coumarin dervatives. XXI. On the preparation of 3-coumarinacetamide and 3,4-dihydro-2-oxo-2H-benzopyran-3-carboxamide derivatives

Abstract

From 3-coumarincarboxylic acid (I) and 3-coumarinacetic acid (III), 3-carboxamides and 3-acetamides were prepared by the use of pyrrolidine, piperidine, and morpholine. Nitration of I and III resulted in introduction of the nitro group into 6-position, the compounds were derived to amides, and reduced catalytically over palladium-carbon, affording 6-amino-3-coumarincarboxamides and -3-acetamides. Catalytic reduction of 3-coumarincarboxamides over platinum oxide resulted in hydrogenation of 3- and 4-positions and gave dihydrocoumarin derivatives. Toxicity of these amides was examined by measuring their SD50, HD50, and LD50 in mice, and it was found that the introduction of an amino group into 6-position of the coumarin ring and hydrogenation of 3-and 4-positions resulted in decrease of the physiological activity as well as the toxicity, that the 3-acetamides have weaker action and weaker toxicity than the 3-carboxamides, and that morpholide is weaker in action and toxicity than pyrrolidide and piperidide.