A Modified Method for the Synthesis of Thiopheneacetic Acid Derivatives from Aromatic Thioamides

Thiophene derivatives are of significant importance in medicinal chemistry owing to their broad spectrum of biological and pharmacological activities. However, the preparation of thiopheneacetic acid derivatives via existing methods remains challenging, typically requiring multiple synthetic steps, harsh conditions, and prolonged reaction times. In this study, a modified and efficient method for the synthesis of thiopheneacetic acid scaffolds is presented. The target compounds were prepared from the reaction of aromatic thioamides possessing an active methylene group with β-bromo-β-aroylpropionic acids in DMF at 90 °C. The optimal reaction conditions, including solvent, temperature, base amount, and molar ratio of starting materials, were systematically investigated to maximize efficiency. Under the optimized conditions, a series of structurally diverse thiopheneacetic acid derivatives were synthesized in good isolated yields (62–80%) within short reaction times (60 min). The progress of the reactions and the purity of the synthesized products were successfully monitored and confirmed using thin-layer chromatography (TLC) and melting point measurements. This method offers a straightforward and practical approach to thiopheneacetic acids, providing advantages over conventional multi-step protocols in terms of operational simplicity and reduced reaction time. The improved synthetic efficiency aligns with the principles of green chemistry and SDG 12 (Responsible Consumption and Production).