Synthesis 2007(22): 3535-3541  
DOI: 10.1055/s-2007-990851
PAPER
© Georg Thieme Verlag Stuttgart · New York

Holzapfel-Meyers-Nicolaou Modification of the Hantzsch Thiazole Synthesis

Eleanor A. Merritt, Mark C. Bagley*
School of Chemistry, Main Building, Cardiff University, Park Place, Cardiff, CF10 3AT, UK
Fax: +44(29)20874030; e-Mail: Bagleymc@cardiff.ac.uk;
Further Information

Publication History

Received 2 August 2007
Publication Date:
29 October 2007 (online)

Abstract

Modified conditions for Hantzsch thiazole synthesis provides valine- and threonine-derived thiazoles without significant loss of optical purity. This two- or three-step procedure proceeds by the cyclocondensation of the corresponding thioamide under basic conditions, according to modified methods of Meyers and Holz­apfel. The hydroxythiazoline intermediate is then dehydrated by treatment with trifluoroacetic anhydride-pyridine, followed by triethylamine, according to Nicolaou’s procedure. Solvolysis of the trifluoroacetamide derivative produced in this process can be affected with sodium ethoxide in ethanol to give a reliable method for the stereoselective synthesis of functionalised thiazole building blocks in high yield.