Microwave induced synthesis of fluorobenzamides containing thiazole and thiazolidine as promising antimicrobial analogs

New 5-arylidene derivatives, which bear a fluorine atom in the 4th position of the benzoyl group as starting compound, have been synthesized by the condensation of 4-fluoro-N-(4-methyl-5-(2-(4-oxo-3-phenylthiazolidin-2-ylidene)hydrazinecarbonyl)thiazol-2-yl)benzamide and Knoevenagel condensation with aromatic aldehydes to form N-(5-(2-(5-(arylidene)-4-oxo-3-phenylthiazolidin-2-ylidene)hydrazinecarbonyl)-4-methylthiazol-2-yl)-4-fluorobenzamides (6a–o) through conventional and microwave methods. The structures of synthesized compounds were established by spectroscopic as well as spectrometric techniques (IR, 1H NMR, 13C NMR, 19F NMR spectroscopy and mass spectrometry). Antimicrobial screening of 5-arylidene derivatives 6a–o was done against Gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and fungi (Candida albicans, Aspergillus niger, and Aspergillus clavatus) using serial broth dilution method. Compounds 6g and 6j were found to be most active at MIC 12.5 μg/mL against selected bacterial strains and compound 6e was found to be most active at MIC 25 μg/mL against selected fungal strains. It has been further observed that the presence of fluorine atom at the 4th position of the benzoyl group in the final compounds is essential for enhancing the antimicrobial activity.

Graphical abstractA series of N-(5-(2-(5-(arylidene)-4-oxo-3-phenylthiazolidin-2-ylidene)hydrazinecarbonyl)-4-methylthiazol-2-yl)-4-fluorobenzamides have been synthesized and screened for in vitro antimicrobial activity.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of fluorine containing thiazole based thiazolidine compounds. ► Compounds were synthesized by MWI method. ► Compounds were characterized adequately by various spectral data. ► Newly synthesized compounds exhibited potential antimicrobial activity.