Simple Access to 2,5-Disubstituted Thiazoles via Cyclisation of N-Substituted α-Amino Acids

02 May 2025, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

We report a mild, metal-free synthesis of 2,5-disubstituted thiazoles from readily available N-substituted α- amino acids. The reaction proceeds via carboxylic acid activation with thionyl chloride, followed by intramolecular cyclisation and in situ sulfoxide deoxygenation, affording the target thiazoles in excellent yields. This transition-metal-free, robust, and scalable protocol enables access to a broad range of 2,5-disubstituted thiazoles, bypassing the need for complex reagents and significantly simplifying their synthesis.

Keywords

Thiazole
α-amino acids
heterocyclic chemistry

Supplementary materials

Title
Description
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Title
2025-04-29-ChemRxiv-ESI
Description
Procedures and full characterization data (NMR, MS, SCXRD as appropriate) for all new compounds and sup-plementary discussion.
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