Chlorine reaction with thioamides

Of all the methods described for the synthesis of thiazole compounds, the most efficient involves the condensation of equimolar quantities of thiourea and a-halo ketones or aldehydes to yield the corresponding 2-aminothiazoles (Scheme 167) (l888LA(249)3l). The reaction occurs more readily than that of thioamides and can be carried out in aqueous or alcoholic solution, even in a distinctly acid medium, an advantage not shared by thioamides which are often unstable in acids. The yields are usually excellent. A derived method condenses the thiourea (2 mol) with the non-halogenated methylene ketone (1 mol) in the presence of iodine (1 mol) or another oxidizing agent (chlorine, bromine, sulfuryl chloride, chlorosulfonic acid or sulfur monochloride) (Scheme 168) (45JA2242). 

Hofmann s classical synthesis of 3,5-disubstituted 1,2,4-thiadiazoles by the oxidation of thioamides (1869)3 continues to be further exemplified. The oxidants employed include iodine,9-11 bromine,12 chlorine,13 and nitrous acid,14 as well as /V-chlorobenzamidine (which is recovered as benzamidine)15 and IV-sulfinyl-p-toluenesulfonamide (which evolves sulfur dioxide in the process).16 Irradiation with UV light in the presence of oxygen effects the same reaction, but has not been used on a preparative scale.17... 

The reaction of thioamides with suitable chlorinating agents, such as phosphorus halides, thionyl chloride, carbonyl chloride, etc., is perhaps the most general method of synthesis of imidoyl chlorides. However, this method has been used only in very few instances because thioamides are less readily available than amides. 

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