Hantzsch thiazole synthesis

What is Hantzsch thiazole synthesis?

In 1887, Hantzsch and Weber first reported a chemical reaction that involves the condensation of α-haloketones (or aldehydes) with thioamides to form thiazole derivatives, which is now commonly known as the Hantzsch thiazole synthesis. Other names for this reaction include the Hantzsch synthesis, Hantzsch reaction, and Hantzsch thiazole reaction.

Hantzsch thiazole synthesis - general reaction scheme - Hantzsch synthesis - Hantzsch reaction - Hantzsch thiazole reaction
Hantzsch thiazole synthesis

While thioamides are the preferred reagents, other thio-ketone derivatives can also be used. The reaction proceeds due to the strong nucleophilicity of the sulfur atom in the thioamide or thio-ketone reagent, but substituted thiazoles may yield lower yields due to dehalogenation. The intermediate steps of the reaction have been isolated at low temperatures, with the dehydration of cyclic intermediates being the slow step.

Modifications to the reaction have been made to reduce or eliminate epimerization, which can occur under certain reaction conditions. Additionally, α-tosyloxyketones can be used as a replacement for α-haloketones in this reaction.

References

Hantzsch, A. and Weber, J.H. (1887), Ueber Verbindungen des Thiazols (Pyridins der Thiophenreihe). [On compounds of thiazole (pyridine of the thiophene series)] Ber. Dtsch. Chem. Ges., 20: 3118-3132. https://doi.org/10.1002/cber.188702002200

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