Synthesis and antimicrobial screening of heterocycles derived from 3-[(4-benzyloxy)phenyl]-1- (3-chlorophenyl)prop-2-ene-1-one

Abstract

Starting from the title enone (whose single crystal X-ray structure is being reported herein), a small library of structurally diverse heterocycles has been assembled through ring closure reactions with the view to evaluate their antimicrobial activity. A multi-step sequence comprising the reaction of the mentioned chalcone analogue with hydrazine, the N-acylation of the resulting pyrazoline with bromoacetyl bromide and the replacement of the easily leaving halogen atom in the acylated pyrazoline with a 4-methylumbelliferone moiety afforded a pyrazoline–coumarin hybrid. Investigation of the reaction of this chalcone analogue with guanidine allowed the isolation of a 2-aminopyrimidine derivative, while an imidazolone was obtained from guanidine and the epoxide of the chalcone analogue. Cyclocondensation of the chalcone analogue with 2-aminobenzenethiol yielded the expected benzothiazepine derivative. Reaction of the chalcone analogue with malononitrile in the presence of sodium methoxide in methanol led to a mixture of two structurally related pyridines. The heterocycles obtained from the title chalcone analogue were devoid of antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans at a concentration of 100 mg/mL.