Action of Labile Nitrogen

3-Thiocyanato-2-aminothiophenes give by ring closure the corresponding 2-aminothieno[2,3d]thiazoles (764). 

The method has not been studied extensively and is restricted to the preparation of alkyl-, aryl-, or alkoxy-substituted thiazoles mostly in 2-, 5-, or 2,5-positions. Yields ranged from 45 to 80%. Sometimes this method gives good results when the usual Hantzsch s synthesis fails. There has been very little speculation about the mechanism of this reaction. 

5-Arylthiazoles were prepared either from w-formaminoaceto-phenones and phosphorus pentasulfide in 70% yield (47, 641) or by treating thioformaminoketones with concentrated sulfuric acid in water (344). Thioformaminoacetophenone itself was obtained by the action of potassium dithioformate on aminoacetophenone (251). 

The Gabriel s synthesis is also applicable when a polysubstituted thiazole is required (381, 550). Thus 2,4,5-trisubstituted thiazoles are obtained by treating the corresponding a-acylaminoketones with phosphorus pentasulfide for a few minutes at 100°C (550) or at higher temperature for heavier substituents (381). (Table 11-31). 

TABLE 11-31. THIAZOLES FROM -ACYLAMINOKETONES AND PHOSPHORUS PENTASULFIDE (Gabriel s synthesis) 

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