Benzyl chloride, with aminothiazoles

Carbocations derived from the alcohol are probably the reactive species, but data concerning by-products expected with carbocationic intermediates are lacking. Rearrangement of 2-alkylaminothiazoles to 2-amino-5-alkylthiazoles may also explain the observed products 2-aminothiazole with benzyl chloride yields first 2-benz Iaminothiazole (206). which then rearranges to 2-amino-5-benzvlthiazole (207) (Scheme 130) (163. 165. 198). 

Carbon disulfide readily reacts with a-aminonitriles giving 2-mercapto-5-aminothiazoles (213), (271, 293) which can be converted to 5-aminothiazoles unsubstituted in the 2-position (Scheme 110 and Table II-34a). If this reaction is carried out in the presence of benzyl chloride in phosphorus tribromide, a 2-S-substituted thiazole derivative (214) is obtained in quantitative yield (Scheme 111), with R = hydrogen or phenyl (68, 304). 

Alkylation, of 2-acetamidothiazoles, 35, 37 with alkali amides, 34, 35 of alkylaminothiazole, 34 with alcohols, 47, 80, 90 of aminothiazoles, with alcohols, 38 with benzyl chloride. 33 with chloracetic acid, 33 with chloracetic esters, 33 with 3-chloropropionic acid, 33 with dimethylaminoethylchloride, 35 with ethylene oxide, 34, 38 with ethyl iodide, 33 with phenethyl chloride, 35 with 2-propynyl bromide. 32 in aprotic solvents, 35 of azothiazoles, 105... 

In the uncondensed imidazoles the standard method reacts an a-aminocarbonyl compound with a thiocyanate (see Section 4.1 and Table 4.1.1). If a 2-alkylthioimidazole is required directly, one can combine an N-alkyT or A -arylcarbonimidodithioate in refluxing acetic acid with the aminocarbonyl substrate (see Section 4.1 and Scheme 4.1.3). Alternatively, reaction between thiourea and a two-carbon synthon (ot-hydroxy-, a-halogeno-, a-dicarbonyl) leads to imidazoline-2-thiones (see Section 4.3). In sulfuric acid, 3-butynylthiourea cyclizes to 4,5-dimethylimidazolin-2-thione (see Section 2.2.1). 1-Substituted 2-methylthioimidazoles can be made, albeit in rather poor yields, from appropriately substituted 2-azabutadienes (see Section 3.2 and Scheme 3.2.3), and 2-arylthioimidazoles are available in moderate yields from benzyl isocyanides and arylsulfenyl chlorides (see Section 4.2 and Scheme 4.2.12). Ring transformations of 5-amino-2-alkylaminothiazoles and 2-acylamino-5-aminothiazoles may have occasional applications (see Section 6.1.2.7). The ease with which a thiol group or imidazole or benzimidazole can be alkylated, in comparison with the annular nitrogens, usually makes it more convenient to prepare alkylthioimidazoles from the thiols (or thiones). 

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