The following procedure is adapted from C. A. Hunt et al. J. Med. Chem. 1994, 37, 240-247. chlorosulfonic acid (240 mL, 3.594 mol) was added to a three-necked round-bottomed flask equipped with a mechanical stirrer, air condenser, dropping funnel, and moisture-proof tubing. Phosphorus pentachloride (PCl5, 300 g, 1.44 mol, 0.40 eq.) was added in batches with stirring, taking 45 minutes. During the addition process, a large amount of hydrogen chloride gas was violently released, but the temperature of the mixture did not rise significantly (<40 °C). When all the PCl5 was added, an almost clear light yellow solution was formed with only a few solid fragments suspended in it. Stirring was continued until gas escape ceased (~0.5 h). Subsequently, the reaction vessel was cooled in an ice bath and 2-chlorothiophene (66.0 mL, 0.715 mol) was slowly added through a dropping funnel over a period of 1.0 hour. After the addition of the first few drops of 2-chlorothiophene, the mixture changed to a dark purple color, and when all the thiophene was added, a dark purple solution was formed. Hydrogen chloride gas was continuously released at a slow rate during the addition. The reaction mixture was stirred at room temperature overnight. Subsequently, the dark purple clear solution was added dropwise to crushed ice (3 L) over a period of 0.5 hours. The purple color disappeared instantly, except for the ice, and a colorless dilute emulsion was formed, which was mechanically stirred at room temperature for about 1 hour. Next, the mixture was extracted with dichloromethane (CH2Cl2, 3 x 300 mL). The combined dichloromethane extracts were washed sequentially with water (1 × 200 mL), saturated sodium bicarbonate solution (NaHCO3, 1 × 250 mL), and brine (1 × 100 mL), dried over anhydrous sodium sulfate (Na2SO4), and concentrated on a rotary evaporator to give the crude product as a pale white to pale yellow viscous mass, which gradually solidified into a semi-solid. Finally, it was purified by high vacuum distillation (boiling point 110-112 °C, pressure 712 mmHg) to obtain 135.20 g (88% yield) of 5-chlorothiophene-2-sulfonyl chloride as a colorless to light yellow semi-solid.
