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

An improved synthetic strategy for 1-substituted 4-H phthalazines using a convenient, three-step re-action 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 acylhy-drazides 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. (C) 2022 Elsevier Ltd. All rights reserved.

Automated summary

This article describes an improved synthetic strategy for synthesizing 1-substituted 4-H phthalazines under mild conditions. The method has high practical value and can be used to synthesize various analogs.