Cyanamides, with 4-aminothiazoles

Cyanamide (227), Rj = NH2, condensed with a-mercaptoketones gives the corresponding 2-aminothiazoles (527). 

Aminothiazole derivatives (243) can be prepared by treatment of enamines of type 240 with sulfur and cyanamide at room temperature in ethanol (701) yields range from 30 to 70%, and no catalyst is required. Initial formation of the thiolated intermediate (241) is probably followed by addition of cyanamide, yielding 242 (Scheme 124). 

Cyanamide (279 R2 = NH2) condenses with a-mercapto ketones to give the corresponding 2-aminothiazoles. 

Oxathiolylium salts (317) condense with cyanamide in the presence of sodium ethoxide to give an open-chain intermediate (318) which cyclizes to substituted 4-aminothiazoles (319 Scheme 211) (73JPR497). 

Reaction of 1,3-oxathiolium salts (264) with cyanamide in the presence of sodium ethoxide produces also substituted 4-aminothiazoles (265) (Scheme 136) (777). 

Heating an enamine with sulphur and cyanamide produces a fused 2-aminothiazole. 

The interaction of enamines with sulphur in conjunction with carbon disulphide, isocyanates, or isothiocyanates results in the production of sulphur-containing heterocyclics. Cyanamide has now been shown to participate in this reaction. Treatment of enamines of type (24) with sulphur and cyanamide at room temperature in ethanol produces a range of 2-aminothiazoles (27) in 30—70% yield no catalyst is required. Initial formation of the thiolated intermediate (25) is probably followed by addition of cyanamide, yielding (26) elimination of amine finally produces the observed thiazoles (27). Since AW-dialkylcyanamides do not undergo this reaction, cyanamide may react as the tautomeric carbodi-imide. An actual example of the reaction employing the enamine derived from cyclohexanone and morpholine is also shown [(28) - (29)]. ... 

Type J (C—S—C—N—C) Syntheses.—In common with their ir-isoelectronic pyrylium analogues (32), 1,3-oxathiazolium salts (33) are convertible into other ring-systems under the influence of nucleophiles. Their reaction with cyanamide in the presence of sodium ethoxide produces substituted 4-aminothiazoles (36) it probably involves the initial addition of the nitrile moiety at C-2, followed by ring-scission to (35), and recyclization to (36). ... 

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