Facile synthesis of 1-substituted 4-H phthalazine, a versatile scaffold for chemically diverse phthalazines

Abstract

An improved synthetic strategy for 1-substituted 4-H phthalazines using a convenient, three-step reaction sequence under mild conditions is described. The protocol involves condensation of hydrazine hydrate with o-ketobenzaldehydes derived through the Pb(OAc)4 oxidation of the N-acylhydrazones of salicylaldehydes. This pathway is of high practical value since a wide variety of substituted acylhydrazides and salicylaldehydes, the substrates for N-acylhydrazones, are commercially available. In addition, the three-step sequence could be scaled up without the need for intermediate purification affording a broad range of products in high yield. 1-Phenyl 4-H phthalazine was a versatile compound providing ready access to multiple phthalazine analogs, including the vasodilating agent MY5445.