Reductive Cyclization of Hydrazones.

D U R I N G investigation of the preparation of substituted hydrazines ( I ) , as potential monoamine oxidase (MAO) inhibitors, we noted the facile reductive cyclizations of the hydrazones of several aliphatic y and {-keto-carboxylic acids. The compounds, listed in Table I , were prepared by the condensation of the appropriate keto-carboxylic acid with either ethyl carbazate ( 2 ) , acetylhydrazine ( 3 ) or semicarbazide in a suitable solvent. The resultant hydrazones (I) were reduced catalytically to give excellent yields (71-9570) of the corresponding cyclized hydrazines (11). In general, the reaction conditions were similar, and a representative preparation is given in the experimental section. Pharmacological testing of these cyclized hydrazines (I1 A-C) indicated LD,,, P.o., in mice of greater than 1000 mg./kg. They exhibited no evidence of M A 0 inhibition, by the "reserpine-challenge'' test ( 4 ) , a t doses up to 100 mg./kg.