2-Chloropyridine-3-sulfonyl chloride

Synthesis

2-Chloropyridine-3-sulfonyl chloride can be prepared by diazotization of 3-amino-2-chloropyridine as a reactant, or by reacting 2-chloro-3-[(2-chloropyridin-3-yl)dithioalkyl]pyridine with hydrochloric acid and chlorine.

Under ice cooling, thionyl chloride (24 mL) was added dropwise to water (140 mL) over 1 hour, and the mixture was stirred at room temperature for 12 hours to obtain a solution containing sulfur dioxide. Independently, under ice cooling, 3-amino-2-chloropyridine (10 g) was added to concentrated hydrochloric acid (80 mL), and the mixture was stirred.

A 25 mL aqueous solution of sodium nitrite (5.75 g) was added dropwise while maintaining an internal temperature not exceeding 5 °C, and the mixture was stirred for another 15 minutes. The reaction mixture was then gradually added at 5 °C to the above solution containing sulfur dioxide and cuprous chloride (140 mg). The mixture was stirred for another 30 minutes under ice cooling, the precipitate was collected by filtration, and washed with water and ethanol to give the title compound 2-chloropyridine-3-sulfonyl chloride (yield 6.99 g, 42%). ¹H-NMR (CDCl₃) delta: 7.54–7.56 (¹H, m), 8.46–8.48 (¹H, m), 8.71–8.73 (¹H, m).

Uses

2-Chloropyridine-3-sulfonyl chloride is mainly used as an intermediate in drug synthesis.