Halocarbonyl derivatives, with 2-aminothiazoles

The N,N-disubstituted thioureas (135) condensed with a-halocarbonyl compounds give 2-disubstituted aminothiazoies (136) but in lower yields (30 to 70%) (Scheme 65 and Table 11-20) (518). For example, N,N-dialkylthioureas condensed with chloroacetaldehyde or dibromoether lead to Ar,At-dialkyl-2-aminothiazoles in 136, Ri=R2 = methyl (342, 404, 436, 637), ethyl (343, 436), n-propyl (518), n-butyl (518), ally] (518), and benzyl (26, 29). When chloroacetone and dichloroacetone are the carbonyl reactants the corresponding 4-methyl (518) and 4-chloromethyl derivatives (572) were obtained. 

Hydroxythiazoles give 2-chIorothiazole derivatives almost quantitatively upon treatment with phosphorus oxychloride (221, 229, 428). This constitutes a convenient synthesis method for these compounds when the conversion of 2-aminothiazoles to 2-chlorothiazole derivatives fails. Esters of thiocarbamic acid or thiourethanes also react with a-halocarbonyl compounds to give the corresponding 2-alkoxythiazoles (50, 68, 209, 272). 

Simple examples of this strategy, which for the synthesis of thiazoles is known as the Hantzsch synthesis, are shown below the syntheses of 2,4-dimethylthiazole where the heteroatoms are provided by thioacetamide, " and 2-aminothiazole, in which 1,2-dichloroethyl ethyl ether is utilised as a synthon for chloroethanal and the heteroatoms derive from thiourea. " The use of thioureas as the sulfur component with 2-chloroacetamides as the second unit gives rise to 2,4-diaminothiazoles. " Conversion of 1,3-diketones into their 2-phenyliodonium derivatives and reaction of these with thioureas produces 2-amino-5-acylthiazoles. The first step in such ring syntheses is 5-alkylation. " A useful variant is the use of an a-diazo ketone in place of the a-halocarbonyl component. " ... 

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