Green Chemical Synthesis and Biological Evaluation of Novel N-substituted Rhodanine Derivatives as Potential Antifungal Agents

Background and purpose: In medicinal chemistry, molecules containing rhodanine(2-thiazolidine-4-one) ring as a magic multifunctional privileged structural and functional scaffold show a broad range of potent pharmacological properties containing anti-microbial, antiviral, anti-diabetic, and anti-convulsant effects. Evidence suggests that the activity of the rhodanine derivative correlates with the size and the nature of the substituents at C-5 and N-3 positions. In this study, we synthesized new N-substituted rhodanine derivatives with arylidene substituent at the C-5 position via solvent-free Knoevenagel condensation reaction. We also investigated the antifungal activity of the compounds. Materials and methods: A mixture of aromatic aldehyde (1 mmol) and rhodanin derivatives (1 mmol) was stirred in choline chloride (ChCl)/urea deep eutectic solvent (1 mL) at 100C in an oil bath for 1 hour. The progress of the reaction was monitored by TLC (2:1 n-hexane/ethyl acetate). Then, the crude compound was collected by vacuum filtration and washed using ice-cold solvent. Results: Novel products were elucidated on the basis of elemental analyses as well as FTIR, Mass and 1H NMR, 13CNMR spectroscopy. Conclusion: A green, comfortable and rapid procedure has been developed for the synthesis of N-substituted rhodanine derivatives using ChCl/Urea Deep Eutectic Ionic Liquid (DEILs) under solvent-free conditions.