Coupling of Thiols and Aryl Halides Mediated by Dicyclohexano-18- crown-6 and Potassium Carbonate

Abstract

Aims: A simple, transition-metal-free C-S coupling protocol for the synthesis of aryl thioethers is reported. Background: Sulfur-containing moieties are ubiquitous in pharmaceutical drugs and materials and therefore methods for their construction are of great importance. One approach entails the catalytic coupling of an aryl halohydrocarbon with a thiol, but the transition metal catalysts usu-ally used are prone to poisoning by participating sulfur species and efficient catalysis is usually only achieved after complex ligand optimization. Objective: New transition-metal-free approaches to the synthesis of C-S bonds are urgently need. Method: We screened the reaction conditions such as alkali, crown ether, solvent, temperature, etc., tested the compatibility of the reaction substrate, and analyzed the mechanism process. Result: The optimized reaction conditions were determined to be 1.0 equiv of aryl halides and 1.2 equiv of thiols at 110 ℃ in toluene with K2CO3 (1.5 equiv) as a base, promoted by 10 mol% dicyclohexano-18-crown-6. Up to 33 examples of thioethers were synthesized under transition-metal-free conditions in good to excellent yields. Conclusion: We have developed a simple and efficient method for the C-S cross-coupling of a wide variety of (hetero)aryl halides and thiols mediated by dicyclohexano-18-crown-6 and with-out the need for transition-metal catalyst. In addition, the preparation and gram-scale experi-ments of a variety of drug molecules further verify the practicability of our developed method.