Novel nosylation reagent mediated highly efficient synthesis, DFT approach and biological activities of sulfonamides

The study reports a highly efficient, eco-friendly method using a novel reagent, N-pyridinium nosyl chloride ([DMAPNS]+Cl-), for the rapid synthesis of sulfonamides under mild conditions. Equimolar reactions of the reagent with various amines in dichloromethane at room temperature were completed within 15 minutes, affording isolated yields of up to 97% without the need for chromatographic purification. Density functional theory (DFT) calculations at the B3LYP/6-311G level were performed to examine the electronic structures and reactivity of the pyridinium salts. Key quantum chemical parameters such as EHOMO, ELUMO, energy gap (ΔE), electron affinity (EA), ionization potential (IP), global electrophilicity index (ω), dipole moment (µ), softness (S), chemical hardness (η), and absolute electronegativity (χ) were evaluated to interpret molecular stability and reactivity trends. Among these, compound 18 exhibited the highest ionisation potential (7.84 eV) and hardness (2.05 eV), indicating enhanced chemical stability. . Antibacterial screening against selected MTCC and NCIM strains showed that compounds 4, 8, 12, 16 and 18 displayed strong broad-spectrum activity, while compounds 14, 20, and 22 exhibited moderate effects. The integration of synthetic methodology, quantum chemical analysis, and biological evaluation highlights the potential of this nosylation approach for the design of future sulfonamide-based therapeutics.