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. 

Ketones such as methyl cyclohexyl ketone 1284 react with DMSO/TCS 14, via their enol form, to give 21% of the chloroketone 1285 a and 63% of the a-methyl mercaptoketone 1286 [70]. Reaction of 1284 with DMSO/MesSiBr (TBS) 16 affords 85% of the bromo compound 1285 b and 12% hexahydrophenacyl bromide 1287 but no 1286 [71]. Whereas reaction of tra s-4-phenyl-3-buten-2-one (benzalacetone) 1288 with DMSO/TCS 14 gives 81% of the sulfonium salt 1289 [70], the y9-dicar-bonyl compound ethyl acetoacetate furnishes 69% of 1290 [70]. In contrast with DMSO/TCS 14, the combination DMSO/TBS 16 effects selective monobromina-tion of y9-dicarbonyl compounds [71] (Scheme 8.28). 

Finally, fox urine and feces contain sulfur compounds that stress rats. In several mercaptoketones, the thiol (mercapto) group was essential for the effect, while the keto group was not (Vernet-Maury etal, 1984). 

Fox feces contain trimethylthiazoline (Fig. 3.1 p. 37), which by itself induces in rats even stronger fear responses than whole feces (Vernet-Mauiy, 1980). Of 12 compoimds from fox feces tested, seven elicited fear responses, confirmed by postmortem corticosterone measurements. Some structure-activity relationships emerged. The thiol group is essential, while theketo group is not molecular size can vary mercaptoketones can be aliphatic or alicyclic the thiol can be secondary or tertiary and the thiol can be alpha or beta to the keto group (Vemet-Maury etal, 1984). 

Hassig, C.A., Symons, K.T., Guo, X., Nguyen, P.-M., Annable, T., Wash, P.L. et al. (2008) KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo Mol. Cancer Therapeutics, 7, 1054-1065. 

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>. 

A number of furans with thiol, sulphide or disulphide substitution have been reported as aroma volatiles, and these are particularly important in meat and coffee. In the early 1970s, it was shown that furans and thiophenes with a thiol group in the 3-position possess strong meat-like aromas and exceptionally low odour threshold values [50] however, it was over 15 years before such compounds were reported in meat itself In 1986,2-methyl-3-(methylthio)furan was identified in cooked beef and it was reported to have a low odour threshold value (0.05 pg/kg) and a meaty aroma at levels below 1 pg/kg [51]. Gasser and Grosch [52] identified 2-methyl-3-furanthiol and the corresponding disulphide, bis(2-methyl-3-furanyl) disulphide, as major contributors to the meaty aroma of cooked beef. The odour threshold value of this disulphide has been reported as 0.02 ng/kg, one of the lowest known threshold values [53]. Other thiols which may contribute to meaty aromas include mercaptoketones, such as 2-mercapto-pentan-3-one. 2-Furylmethanethiol (2-furfurylmercaptan) has also been found in meat, but is more likely to contribute to roasted rather than meaty aromas. Disulphides have also been found, either as symmetrical disulphides derived from two molecules of the same thiol or as mixed disulphides from two different thiols [54]. 

The equilibrium between mercaptans and a,fl-unsaturated ketones (9) can be followed by measuring the cathodic waves of the unsaturated ketones, or of the p-mercaptoketones formed, or by measuring the anodic waves of the mercaptans (73). 

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,... 

Figure 8 outlines possible routes leading to cysteine specific products via 1-deoxypentosone. Under the chosen reaction conditions, (180 °C H-O) norfuraneol is further transformed via 4-hydroxy-5-metnyl-3-(2H)-thiophenone and 2-methyl-3-(2H)-thiophenone, into 2-methyl-3-mercapto-thiophene and 2-methylthiophene, respectively. Norfuraneol is a methylene active compound, which undergoes aldolcondensation with carbonyls forming colored nonvolatile products. 2-Mercaptopropionic acid may be formed from the mercaptoketone by oxidative cleavage. By this route 2-methyl-3-thiolanone and 2-methyl-4,5-dihydro-thiophene may result. 

As the final pH of meat increases above the normal range of 5.6-5.8, there is a decrease in meat flavour.101102 The reaction between norfuraneol and cysteine, which plays a crucial role in meat flavour, is very sensitive to pH.103 At pH 4.5, the major volatile products are mercaptoketones, furan- and thiophenethiols, 2-methyltetra-hydrothiophenone, and 3,5-dimethyl-l,2-dithiolan-4-one, whereas, at pH 6.5, these compounds were detected, if at all, only in traces, except for the thiophenone however, pyrroles, pyrazines, thiazoles, and oxazoles had achieved prominence. The sensory observations are a clear reflection of such differences. Similar effects of pH had been found for the ribose-cysteine and other systems.104... 

VI. Thiazoles from Nitriles and o-Mercaptoketones or Acids 2.4-Disubstituted... 

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