Microwave-Assisted Synthesis and Antifungal Activity of Novel Substituted Azetidinone Derivatives of Edaravone

Abstract

This paper describes development of new chemical entities of edaravone. The chemical name of edaravone is 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one. The starting material 3-methyl-1-substituted-1H-pyrazol-5(4H)-ones (1) were synthesized in high yields by the treatment of ethyl aetoacetate with appropriate 1-phenylhydrazine. Ethyl-2-(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)acetate (2) was synthesized by reaction of ethyl chloroacetate with compound (1). 2-(4,5-Dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)acetohydrazide (3) prepared by reaction of hydrazine hydrate with compound (2) in presence of ethanol. The microwave assisted reaction of compound (3) with different substituted aldehydes in presence of ethanol gives N-(substituted benzylidenyl)-[2-(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)acetohydrazide] (4a-4e). The microwave assisted reaction of (4a-4e) with chloroacetyl chloride and triethylamine in presence of DMF gives formation of 2-(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)-acetamide-(3-chloro-4-substituted phenylazetidin-2-one) (DTa-DTe). The products, characterized on the basis of spectral data, have shown moderate to good antifungal activity against bacteria and fungi.