Introduction of Methyl Group in Substituted Isoselenazolones: Catalytic and Mechanistic Study

• Published in: Journal of organic chemistry 2023-04, Vol.88 (7), p.4273-4285
• Main Authors: Kumar, Manish, Chhillar, Babli, Verma, Divya, Nain, Sumit, Singh, Vijay P.
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.2c02831

Copper-catalyzed direct selenation of substituted 2-bromo-N-phenylbenzamide substrates with elemental selenium powder provided a series of methoxy-substituted isoselenazolones via the C–Se and Se–N bond formations. Phenolic substituted isoselenazolones have been obtained by O-demethylation of the corresponding methoxy-substituted analogues using boron tribromide. Some isoselenazolones have been structurally characterized by X-ray single-crystal analysis. The glutathione peroxidase (GPx)-like antioxidant activity of isoselenazolones has been evaluated both in thiophenol and coupled-reductase assays. All isoselenazolones showed good GPx-like activities in the coupled-reductase assay. The ferric-reducing antioxidant power of phenolic antioxidants has also been evaluated. The best phenolic antioxidants were found to be good ferric-reducing antioxidant power agents. The single electron transfer, hydrogen atom transfer, and proton-coupled electron transfer mechanisms for the antioxidant properties of all catalysts have been supported by density functional theory calculations. The catalytic cycle was proposed for one of the phenolic isoselenazolones involving diselenide, selenenyl sulfide, selenol, and selenenic acid as intermediates using 77Se­{1H} NMR spectroscopy.