PYRAZOLIDINE-3, 5-DIONE AND 2-METHYL-4-OXO-4H-THIOCHROMENE-8-CARBONYL CONJUGATES: SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL SCREENING

In this study, a novel series of heterocyclic compounds containing pyrazolidine-3, 5-dione nucleus has been synthesized. The compounds were synthesized in four steps; esterification of 2-mercaptobenzoic acid in an acidic medium to yield 2-mercapto-benzoic acid ethyl ester which was cyclized using ethyl acetoacetate to form 2-methyl-4-oxo-4H-thiochromene-8-carboxylic acid ethyl ester. These were reacted phenyl hydrazine derivatives to give corresponding thiochromene derivatives, which were cyclized using diethylmalonate to obtain pyrazolidine-3, 5-dione derivatives. All the synthesized compounds were characterized by spectral (IR, NMR and MS) and elemental analysis. The compounds were screened for their antibacterial activity against Gram-positive bacteria (B. subtilis, S. epidermidis, M. luteus, S. aureus, B. pumilis, and B. cereus), Gram-negative bacteria (K. pneumonia, E. coli, and P. aeroginosa) and for antifungal activity against (A. niger, C. albicans and F. solani) by agar-diffusion method. The minimum inhibitory concentrations (MICs) of these compounds were also determined by tube dilution method. The antimicrobial effectiveness of all the compounds was found to be concentration dependent. Two compounds- 1-(3-chlorophenyl)-2-(2-methyl-4-oxo-4H-thiochromene-8- carbonyl) pyrazolidine-3, 5-dione (5a) and 1-(2-methyl-4-oxo-4H-thiochromene-8-carbonyl)-2-p-tolylpyrazolidine-3, 5-dione (5d) exhibited good antibacterial activity. The antibacterial activity of all the compounds was founds to better than the antifungal activity.