Title:Coupling of Thiols and Aryl Halides Mediated by Dicyclohexano-18-
crown-6 and Potassium Carbonate
Volume: 19
Issue: 7
Author(s): Zhong-Lin Liu, Jing-Xiu Xu, Ning Deng*, Zheng Dong, Xiao Shen, Jun Xu and Hua-Jian Xu*
Affiliation:
- School of Food and Biological Engineering, School of Chemistry and Chemical Engineering, Anhui Province Key Laboratory of Advance Catalytic Materials and Reaction Engineering, Hefei University of Technology, Hefei 230009, China
- School of Food and Biological Engineering, School of Chemistry and Chemical Engineering, Anhui Province Key Laboratory of Advance Catalytic Materials and Reaction Engineering, Hefei University of Technology, Hefei 230009, China
Keywords:
Carbon-sulfur coupling, SNAr, aryl halides, thiols, dicyclohexano-18-crown-6, 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 usually
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.
Methods: 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.
Results: 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 transitionmetal-
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 without
the need for transition-metal catalyst. In addition, the preparation and gram-scale experiments
of a variety of drug molecules further verify the practicability of our developed method.
