Synthesis
General procedure for the synthesis of isothiazol-3-one from glycinamide hydrochloride: glycinamide hydrochloride (1 mol) was suspended in N,N-dimethylformamide (DMF, 500 mL), and dichlorosulfoxide (SO2Cl2, 300 mL) was slowly added dropwise over a period of 1.5 h, while cooling to maintain the reaction temperature at 5-10 °C. The reaction was carried out with stirring. After the dropwise addition, the reaction was continued with stirring at 10-15 °C. Subsequently, water (500 mL) was added slowly over a period of 6 hours. After completion of the reaction, the solid insoluble material was removed by filtration and the filtrate was extracted with ether (2 L). The ether extracts were combined and washed with saturated saline (200 mL), followed by evaporation of the solvent under reduced pressure to give a light yellow solid (132 g, Product A). The aqueous layer was extracted with dichloromethane (DCM, 2 x 600 mL), and the DCM extracts were combined and washed with ether and water sequentially. The organic layer was then washed with saturated saline and the solvent was evaporated under reduced pressure to give a milky white solid (18 g, Product B). Products A and B were combined, dissolved in ether, dried by adding desiccant and decolorized by adding activated carbon. The activated carbon was removed by filtration and the filtrate was evaporated under reduced pressure to give a light yellow solid (104.3 g). The solid was ground with isohexane to give the final isothiazol-3-one (91.3 g, 90% yield). Melting point: 102-105 °C.
