Quality by design-based method to synthesize sulfonamides using LiOH.H₂O

A rapid, systematic and optimized process for the synthesis of sulfonamides was developed using lithium hydroxide monohydrate (LiOH.H₂O) as a base. The study employed a response surface methodology (RSM) approach using a central composite design (CCD) to determine the ideal reaction conditions, specifically base equivalence and temperature. A series of 13 experimental runs identified the most efficient conditions as 0–5°C with 0.5 equivalents of LiOH.H₂O, resulting in very good to excellent yields within 1–8 min. The optimized reaction parameters significantly reduced reaction time while maintaining high selectivity and yield. Compared to conventional base-mediated sulfonamide synthesis, this approach minimizes excess reagent usage, enhances reaction efficiency, and supports sustainable synthetic methodologies.