A Straightforward Route to Potent Phenolic Chain-Breaking Antioxidants by Acid-Promoted Transposition of 1,4-Benzo[b]oxathiines to Dihydrobenzo[b]thiophenes

Abstract

The transformation of simple phenols with limited antioxidant activity into potent chain-breaking antioxidants was achieved by a three-step protocol, consisting of the conversion of phenols into 1,4-benzo[b]oxathiines followed by an unprecedented acid-promoted transposition to o-hydroxydihydrobenzo[b]thiophenes, or dihydrobenzo[de]thiochromenes, starting from phenols or naphthols, respectively. These derivatives, bearing a benzo-fused heterocycle with a sulfide sulfur ortho to the phenolic OH, have a rate constant of reaction with alkylperoxyl radicals (kinh ) comparable to that of α-tocopherol. A solid rationale for the transposition mechanism as well as for the structure-antioxidant activity relationship is presented.

Keywords: S heterocycles; antioxidants; electrophilic substitution; phenols; vitamins.