Thiourea Dioxide-Mediated N−O Bond Cleavage in Hydroxamic Acids for the Selective Synthesis of Primary Amides

Abstract

Thiourea dioxide (TDO), a sustainable and cost-effective industrial compound, has been demonstrated as a bifunctional reagent for efficient hydroxyl activation and N–O bond cleavage of hydroxamic acids, enabling the efficient synthesis of primary amides with excellent functional group compatibility. This straightforward process has been successfully applied to the gram-scale synthesis of niacinamide. Furthermore, mechanistic studies suggested that the N–O bond cleavage involves a cascade process of sulfenylation and reduction. This novel and robust transformation gives a new lease of the synthetic utility of TDO as an innocuous and versatile reagent in organic chemistry.

Keywords

Thiourea dioxide - Hydroxamic acids - Primary amides - N−O bond cleavage - Cascade process

Publication History

Received: 27 March 2025

Accepted after revision: 16 May 2025

Accepted Manuscript online:
16 May 2025

Article published online:
23 July 2025

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