Oxidative radical coupling of hydroquinones and thiols using chromic acid: one-pot synthesis of quinonyl alkyl/aryl thioethers

Abstract

An efficient, simple and practical protocol for one-pot sequential oxidative radical C–H/S–H cross-coupling of thiols with hydroquinones (HQs) and oxidation leading to the formation of quinonyl alkyl/aryl thioethers using H₂CrO₄ was developed. This cross-coupling of thiyl and aryl radicals offers mono thioethers in good to moderate yield and works well with a wide variety of thiols. Similarly, this method works well for coupling of 2-amino thiophenol and HQs to form phenothiazine-3-ones 5a–c. C–S bond formation via thioether synthesis was observed using a chromium reagent for the first time. Theoretical studies on the pharmacokinetic properties of compounds 5a–c revealed that due to drug-like properties, compound 5b strongly binds with Alzheimer's disease (AD) associated AChE target sites.