Synthesis of 2-[(5-benzyl-1,3,4-oxadiazole-2yl)sulfanyl]-N- (arylated/arenylated) acetamides as antibacterial and acetyl cholinesterase inhibitors

Abstract

The synthetic methodology is carried out in multistep which was initiated as phase I by utilizing Fischer esterification methodology of 2-phenylacetic acid (1) to ethyl-2-phenylacetate (2). The ester was reacted with hydrazine hydrate form 2-phenylacetohydrazide (3) which underwent ring closure with carbon disulfide in alcoholic base to achieve 5-benzyl-1,3,4-oxadiazole-2-thiol (4). Phase II, involved the reaction of electrophiles with 2- bromoacetylbromide (5) with arylated/arenylated amines (6a-e) in aqueous alkaline medium under vigorous shaking to generate N-substituted-2-bromoacetamides (7a-e). Finally in phase III, the parent oxadiazole reacted with N-substituted2-bromoacetamides and in DMF/LiH to yield 2-[(5-benzyl-1,3,4-oxadiazole-2yl)sulfanyl]-N-(arylated/arenylated) acetamides (8a-e). All the derivatives were creened for their anti-enzymatic potential against acetyl/butyrylcholinesterase and lipoxygenase and for the antibacterial activity. They were found to be weak enzyme inhibitors and also possessed weak antibacterial action with the exception of 8e, which demonstrated prominent antienzymatic and antibacterial activity, which may be attributed to the presence of 3,4-dimethoxyphenylacetamide moiety. The LD50 data revealed that most of the N-substituted derivatives were found to be less cytotoxic.