Cook-Heilbron 5-amino-thiazole synthesis

What is Cook-Heilbron 5-amino-thiazole synthesis?

The Cook-Heilbron reaction is a process that involves reacting a-aminonitriles with dithioacid salts and esters, as well as carbon disulfide, carbon oxysulfide, and isothiocyanates, all under very mild conditions. The end result of this reaction is the formation of 5-aminothiazoles.

Cook-Heilbron 5-amino-thiazole synthesis
Cook-Heilbron 5-amino-thiazole synthesis

Before Cook and Heilbron’s 1947 publication describing this innovative synthesis, 5-aminothiazoles were relatively unknown in scientific literature. Previous methods for synthesizing these compounds involved the Curtius degradation of ethyl thiazole-5-carboxylates, but this technique was not widely applicable due to difficulties in obtaining the necessary starting materials. While studying penicillin, Cook and Heilbron discovered that the reaction between methyl dithiophenylacetate and ethyl aminocyanoacetate produced a compound initially believed to be ethyl phenylthionacetamidoyanoacetate.

Cook-Heilbron 5-amino-thiazole synthesis - Ethyl phenylthionacetamidoyanoacetate
Ethyl phenylthionacetamidoyanoacetate

However, further investigation revealed that the compound was actually 5-amino-4-carbethoxy-2-benzyl-thiazol, which exhibited basic properties.

Cook-Heilbron 5-amino-thiazole synthesis - 5-Amino-4-carbethoxy-2-benzyl-thiazol
5-Amino-4-carbethoxy-2-benzyl-thiazol

References

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