Promoting Effect of Crystal Water Leading to Catalyst-Free Synthesis of Heteroaryl Thioether from Heteroaryl Chloride, Sodium Thiosulfate Pentahydrate, and Alcohol

It is observed the crystal water in sodium thiosulfate pentahydrate (Na 2 S 2 O 3 ·5H 2 O) can promote its multicomponent reaction with heteroaryl chlorides and alcohols, providing a facile, green, and specific synthesis of unsymmetrical heteroaryl thioethers via one-step formation of two C–S bonds under catalyst-, additive-, and solvent-free conditions. Mechanistic studies suggest that the crystal water in Na 2 S 2 O 3 ·5H 2 O is crucial in generating the key thiol intermediates and byproduct NaHSO 4, which then catalyzes the dehydrative substitution of alcohols with thiols to afford thioethers.