Heteroaryl thioamides

The annulation reaction is applicable to a variety of aromatic thioamides with both electron withdrawing and donating groups and heteroaryl thioamides such as 2-thienyl and 3-pyridyl. Aliphatic thioamides such as thioacetamide did not undergo clean cyclisation though. When triphenylphosphine was used as the catalyst the reaction required refluxing in toluene however, if more nucleophilic phosphines were used such as tributylphosphine the reaction could be carried out at room temperature <02JOC4595>. 

The reaction of a thioamide with a-halocarbonyl compounds has been applied extensively, and many thiazoles (10) with alkyl, aryl, aralkyl, or heteroaryl functional groups at the three 2-, 4-, or 5-positions have been reported (Scheme 6). 

Ethyl-4,5-thiazole dicarboxylates (77), R =H, Me, Et, Ph, or heteroaryl, were prepared from diethyl-a-chloro-/3-ketosuccinate (76) and thioamides in boiling ethanol (Scheme 35) (103, 110, 145, 298, 577, 639). 

Thiazolium salts with alkyl (103, 722), arylalkyl (116), aryl (305), or heteroaryl (96) substituents on the nitrogen have been also prepared by this procedure. As in the thiazole series, N-substituted thioamides can be formed directly in the reaction mixture from phosphorus pentasulfide and N-substituted amides (127). These methods are important in the synthesis of thiamine 102 (vitamin Bj) (Scheme 45). 

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