The general procedure for the synthesis of N-propylsulfonamide from n-propylamine and chlorosulfonyl isocyanate is as follows: first, chlorosulfonyl isocyanate (12.3 mL, 0.14 mol, 1.0 eq.) was slowly added to a solution of benzyl alcohol (14.7 mL, 0.14 mol, 1.0 eq.) in dichloromethane (DCM, 130 mL) at -35 °C over a reaction time of 30 min. . Subsequently, a solution of n-propylamine (14 mL, 0.17 mol, 1.2 eq.) and triethylamine (29.5 mL, 0.21 mol, 1.5 eq.) in DCM (35 mL) was added slowly and dropwise at -50 °C. The reaction time was 30 minutes. The reaction mixture was gradually warmed to 20 °C and kept at this temperature for 2 hours. Upon completion of the reaction, the reaction mixture was washed sequentially with water, 33% HCl and water. The mixture was then warmed up to 30 °C and the organic and aqueous layers were separated. The organic layer was washed with a mixture of triethylamine (20 mL, 0.14 mol, 1 eq.) and water (50 mL) and the pH was adjusted to be greater than 5. Next, tetrahydrofuran (THF, 85 mL) and 10% Pd/C catalyst (1 g) were added and the hydrogenation reaction was carried out for 6 hr at 25 °C under a pressure of 6 bar hydrogen. At the end of the reaction, the catalyst was removed by Celite filtration. Subsequently, the volatile solvent was removed under reduced pressure and dimethyl sulfoxide (DMSO, 120 mL) was added to dissolve the product. The resulting DMSO solution of propane-1-sulfonamide (100% theoretical yield) was used directly in the next step of the reaction.
