Cook-Heilbron thiazole synthesis

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. 

Cacchi synthesis (indole) 140 Chichibahin reaction 352 Chichibabin synthesis (indolizine) 153 Claisen synthesis (isoxazole) 188 Combes synthesis (quinoline) 399 Cook-Heilbron synthesis (thiazole) 206 Corey synthesis (oxirane) 22 Cornforth rearrangement 171 imino-Corey reaction 36... 

Conidine — see 1-Azabicy,clo[4.2.0]octane Conjugation reactions nitrogen heterocycles at carbon, 1, 239 at nitrogen, 1, 234-238 Conjunction nomenclature, 1, 37 Contagious bovine pleuropneumonia heterocyclic compounds as, i, 205 A Convention nomenclature, 1, 32 Con vi cine occurrence, 3, 144 Cook-Heilbron s synthesis thiazoles, 6, 300-301 Cope rearrangement, 7, 35 Copper... 

V. Thiazoles from a-Aminonitriles (Cook-Heilbron s Synthesis) (T pe II).... 284... 

The synthesis of thiazoles using a-aminonitriles as starting materials is known as the Cook-Heilbron s synthesis. Some variants have been described using other substrates <84CHEC-I(6)300>. 

The thiazole ring can be obtained directly by other methods, but they have limited application. An example is the synthesis of Cook and Heilbron using a-aminonitriles or a-aminoamides and carbon disulfide (or thioacid derivatives) as reactants of type II. 

Prior to the 1947 report by Cook and Heilbron on their novel synthesis, 5-aminothiazoles were mostly unknown in the literature. Previous syntheses included the Curtius degradation of ethyl thiazole-5-carboxylates which did not have general applicability there was also difficultly in obtaining the necessary starting materials. During a study on penicillin, Cook and Heilbron found that the reaction between methyl dithiophenylacetate and ethyl aminocyanoacetate gave what was initially believed to be ethyl phenylthionacetamidocyanoacetate 4. However further studies proved the compound to be 5-amino-4-carbethoxy-2-benzyl-thiazole 5, which was basic. 

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