A-Mercaptoketones

The reaction of phosphorus pentasulfide with a-acylamino carbonyl compounds of type Ilia also yields thiazoles. Even more commonly, a mercaptoketone is condensed with a nitrile of type IVa or a-mercaptoacids or their esters with Schiff bases. This ring closure is limited to the thiazolidines. In the Va ring-closure type, /3-mercaptoalkylamines serve as the principal starting materials, and ethylformate is the reactant that supplies the carbon at the 2-position of the ring. These syntheses constitute the most important route for the preparation of many thiazolidines and 2-thiazohnes. In the Vb t3fpe of synthesis, one of the reactant supplies only the carbon at the 5-position of the resultant thiazole. Then in these latter years new modern synthetic methods of thiazole ring have been developed (see Section 7 also Refs. 515, 758, 807, 812, 822). 

Besides a-halocarbonyl compounds, a-mercaptoketones and acids are also used for the preparation of thiazoies from nitriles and aldehydes oximes. 

Miyatake and Yashikawa have prepared several 2,4-disubstituted thiazoies in fairly low yield (16 to 40%) by the action of a-mercaptoketones (226) on nitriles (227) (Scheme 118 and Table IT38). The reaction was carried out in benzene solution at 0 C by passing a current of dry hydrogen chloride through the mixture. After 3 hr the mixture was filtered and washed with benzene. When the resins had been removed and the remaining solution alkalinized, the product was extracted. 

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

The cyclization of a-mercaptoketones with ammonium thiocyanate leads to the corresponding 2-mercaptothiazoles (144). For example, 2-mercapto-3-pentanone in ethereal solution with sulfuric acid gives 4-ethyl-5-methyl-2-mercaptothiazole (10), Ri = SH, R2 = Et, R3 = Me, when allowed to stand for 3 hr without heating with ammonium thiocyanate. 

IR spectroscopy showed the compound 147 to exist almost completely in the 47/-form however, the minor tautomer can undergo a nucleophilic attack by an a-mercaptoketone to the 3-carbon followed by enamine formation to give 165 (Scheme 6) <1962LA(652)50>. 

Conversion of ketones into the corresponding 2,2-disubstituted-l,3-oxathiolanes with 2-mercaptoethanol is efficiently catalysed by Me3SiOTf and this same catalyst is also effective in promoting the reverse reaction [95TL2285], Treatment of a-mercaptoketones,... 

Cemy, C., Davidek, T. a-Mercaptoketone formation during the Maillard reaction of cysteine and [l- C]ribose. J. Agric. Food Chem. 2004, 52, 958-961. 

Although the precise pathway involved in the aforementioned synthesis has not been established, it is clear that 3,4-dihydro-2//-l, 4-thiazines are formed in preference to thiazolidines, which, in turn, are preferred to 5,6-dihydro-2if-1,4-thiazines. The dihydrothiazines are probably produced from a-mercaptoketones, formed by the action of elemental sulfur upon the ketones, and aziridine. It seems likely that the thiazolidines arise from the reactions of the ketones with )3-mercaptoethyIamine, produced from aziridine and hydrogen sulfide a competing reaction of the a-mercaptoketone with sulfur is probably responsible for the generation of hydrogen sulfide. 

Thiazoles from nitriles and a-mercaptoketones 2,4-disubstituted and 2,4,5-trisubstituted derivatives... 

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