Solvent-free synthesis of novel 1,3-thiazolidin-4-one-5-arylidene derivatives <i>via</i> cyclocondensation

The 1,3-thiazolidin-4-one scaffold is a well-known pharmacophore in medicinal chemistry, valued for its broad spectrum of biological activities. In this study, we report the design and efficient synthesis of a new series of 1,3-thiazolidin-4-one-5-arylidene derivatives <b>7a-j</b>. The synthetic strategy began with the cyclocondensation of phenylhydrazide intermediates (<b>3a</b> and <b>3b</b>) with mercaptoacetic acid under solvent-free conditions, using a few drops of acetic acid. This reaction yielded the key thiazolidinone intermediates (<b>5a</b> and <b>5b</b>). Subsequent condensation with benzaldehyde or its substituted derivatives (<b>6a – j</b>) in the presence of sodium ethanolate (CH₃CH₂ONa) afforded the target compounds (<b>7a – j</b>) in yields ranging from 50% to 86%. The structures of all synthesized compounds were confirmed through details spectroscopic analyses, including ¹H, ¹³C Nuclear Magnetic Resonance (NMR), and High-Resolution Mass Spectrometry (HRMS).