Cook-Heilbron Synthesis of Thiazoles

The Cook-Heilbron synthesis yields 5-amonothiazoles with various substituents on the 2-position of the thiazole. Such a construction is brought about under mild conditions by reacting a-amino nitrile with salts and esters of dithioacids, carbon disulfide, carbon oxysulfide, isothiocyanates, etc. It was discovered by Cook and Heilbron in 1947 prior to which 5-aminothiazoles were less known. 

The reaction has not been extensively applied although a few examples in the literature exist. For example, Scott et al. have used this reaction in the synthesis of thiazolyl bisamide CSF-IR kinase inhibitors for the treatment of cancer. The 2-methyl-5-aminothiazoles with different substituents were prepared via condensation of aminoacetonitrile and ethyl dithioacetate followed by cyclization and then coupled with carboxylic acid to yield bis-amides that were tested for in vivo activity. 

Another example involves an application of this reaction toward the synthesis of purines by Biagi and co-workers. 5-Amino-2-phenylmethylaminothiazole-4-carboxamide was prepared as a substrate for a base-catalyzed thiazole rearrangement to yield a product that could be employed as a starting material for the synthesis of substituted purines. 

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See also in sourсe #XX -- [ ]

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