Cyclization reactions with Hantzsch method

Probably first obtained by Hantzsch and Arapides (105) by condensation of a,/3-dichlorether with barium thiocyanate, and identified by its pyridine-like odor, thiazole was first prepared in 1889 by G. Popp (104) with a yield of 10% by the reduction in boiling ethanol of thiazol-2-yldiazonium sulfate resulting from the diazotization of 2-aminothiazole. prepared the year before by Traumann (103). The unique cyclization reaction affording directly the thiazole molecule was described in 1914 by Gabriel and Bachstez (106). They applied the method of cyclization, developed by Gabriel (107, 108), to the diethylacetal of 2-formylamino-ethanal and obtained thiazole with a yield of 62% - Thiazole was also formed in the course of a study on the ease of decarboxylation of the three possible monocarboxylic acids derived from it (109). On the other... 

The most commonly used method for the preparation of fused thiazoles involves the reaction of a-mercapto N-heterocyclic compounds of type (138) with an a-halocarbonyl compound or ester to give S-alkylated intermediates (139) which can be dehydrated to (140). When R2 is alkoxy, thiazolones (141) are formed (Hantzsch synthesis). Strong dehydrating agents are necessary to cyclize aldehydes and ketones (139) to fused thiazoles. The method has been used to prepare (dihydro) imidazo[2,l-6]thiazoIes and thiazolo[3,2- ]-s-triazoles (80JHC1321, 78JHC401, 82IJC(B)243). 

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