2-Chloro-4-methyl-5- thiazole, preparation

Thiazole itself can be obtained by condensing chloroacetaldehyde and thioformamide (Scheme 159). The reaction is explosive and proceeds in low yield because of the instability of the thioformamide under acid conditions. Higher thioamides are more stable and react under milder conditions with chloroacetaldehyde, affording 2-substituted thiazoles in moderate yields. It is possible, and often preferable, to prepare the thioamide in situ in dioxane solution by the action of phosphorus pentasulfide on the corresponding amide and in the presence of solid MgC03 (Scheme 160). With arylthioamides, except for some nitrothiobenzamides, yields are usually higher and the cyclization is carried out over several hours in boiling absolute alcohol. Chloroacetaldehyde can be replaced in these reaction by derivatives such as 1,2-dichloro- or dibromo-ethyl methyl or ethyl ether, 1,2-dichloro- or dibromo-ethyl acetate, 2-chloro- or dibromo-ethyl acetate, and 2-chloro or bromo-diethyl-acetal. 

The synthesis of hitherto inaccessible thienylpyrazolones has been described. The reaction of (174) with methyl bromoacetate, followed by base-catalysed cyclization, gave (175). The corresponding thiazole-fused system, on the other hand, was prepared through the reaction of 2-phenyl-5-chloro-4-formylthiazole with thioglycollic acid in the presence of sodium methoxide. Another route to thienothiazoles consists in the reaction of (104) with CSa and sodium hydroxide. ... 

According to other synthesis methods, 3 can be prepared by coupling of the N - -dialkylated 2-(N-nitroimino)-hexahydro-l,3,5-triazine (21, R = alkyl, ary-lalkyl) with 2-chloro-5-(ffiloro-methyl)-l,3-thiazole (22, CCMT Table 29.2.1.9) at the 3-position and subsequent ring cleavage reaction of the resulting bis-aminal structure within the sbc-membered system of 23 (Scheme 29.2.1.3) [42, 43, 44]. 

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