The development of efficient, reproducible, and environmentally benign protocols for the synthesis of bioactive heterocycles remains highly desirable, particularly in resource-limited settings. Owing to its structural features and synthetic accessibility, sulfur heterocyclic (SH) compounds were identified as a novel molecule with potential pharmacological relevance. While previous studies have extensively explored solvent polarity and catalytic systems, limited attention has been given to their applicability in semi-urban and remote laboratory environments. This study aimed to (i) optimize the yield of SH using different solvent–catalyst systems, (ii) confirm its structure through IR and ¹H NMR spectroscopy, and (iii) develop a field-appropriate, scalable synthesis protocol. SH was synthesized using various solvent–catalyst combinations, including ethanol–ZnCl₂, DMSO–FeCl₃, and toluene–Cu(OAc)₂, and the reaction yields were compared. Functional group analysis was performed using IR spectroscopy, while structural confirmation was achieved through ¹H NMR analysis. Among the systems evaluated, ethanol–ZnCl₂ afforded the highest conversion, indicating superior catalytic efficiency and solvent compatibility. IR spectra exhibited characteristic NH and CN stretching bands at 3320 cm⁻¹ and 2200 cm⁻¹, respectively. The ¹H NMR spectrum showed aromatic proton signals in the range of 7.2–7.8 ppm and a deshielded NH signal at 9.5 ppm, suggesting intramolecular hydrogen bonding. The protocol demonstrated good reproducibility and suitability for field-level implementation. In conclusion, SH-01, synthesized from benzaldehyde, thiourea, and malononitrile under optimized ethanol–L-proline conditions, was successfully synthesized and structurally validated using accessible and environmentally benign reagents. The developed methodology offers a scalable and sustainable approach for application in resource-constrained laboratories, highlighting the importance of solvent–catalyst synergy and supporting future studies in green chemistry and bioactivity evaluation.

Keywords: One-Pot Synthesis; Sulfur Heterocycles; Green Chemistry; ZnCl₂ Catalysis; Bioactive Scaffolds;