Nucleophilic Aromatic Substitution of Heteroaryl Halides with Thiols

Abstract

The nucleophilic aromatic substitution (S_NAr) between heteroaryl halides (Cl, Br) and thiols proceeds smoothly in DMAc under the action of K₂CO₃ at rt–100 °C. For most electron-deficient heteroarenes, reaction takes place without introducing an additional electron-withdrawing group. For electron-rich heteroarenes, an additional electron-withdrawing group such as a simple ester, keto, cyano, and nitro group is required to ensure the reaction completes. The reactivity trend of heteroaryl halides is highly dependent on the electronic nature of the heteroarenes and orientation of halogens. Besides thiols, a couple of functionalized thioureas and thioamides are compatible with these conditions, providing the corresponding heteroaryl thioethers in good yields.