Related Experiment Video
Updated: Sep 30, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Disentangling the Puzzling Regiochemistry of Thiol Addition to o-Quinones
Maria L Alfieri1, Alice Cariola2, Lucia Panzella1
1Department of Chemical Sciences, University of Naples Federico II, Via Cintia 21, Naples I-80126, Italy.
Abstract:
The addition of thiol compounds to o-quinones, as exemplified by the biologically relevant conjugation of cysteine to dopaquinone, displays an anomalous 1,6-type regiochemistry compared to the usual 1,4-nucleophilic addition, for example, by amines, which has so far eluded intensive investigations. By means of an integrated experimental and computational approach, herein, we provide evidence that the addition of glutathione, cysteine, or benzenethiol to 4-methyl-o-benzoquinone, modeling dopaquinone, proceeds by a free radical chain mechanism triggered by the addition of thiyl radicals to the o-quinone. In support of this conclusion, DFT calculations consistently predicted the correct regiochemistry only for the proposed thiyl radical-quinone addition pathway. These results would prompt a revision of the commonly accepted mechanisms for thiol-o-quinone conjugation and stimulate further work aimed at assessing the impact of the free radical processes in biologically relevant thiol-quinone interactions.
More Related Videos
12:30Synthesis of a Thiol Building Block for the Crystallization of a Semiconducting Gyroidal Metal-sulfur Framework
Published on: April 9, 2018
07:50Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides
Published on: May 26, 2019
Related Concept Videos
Preparation and Reactions of Thiols
Oxidation of Phenols to Quinones
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox...
Preparation and Reactions of Sulfides
Regioselectivity of Electrophilic Additions-Peroxide Effect
Structure and Nomenclature of Thiols and Sulfides
Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids