Thiazolyl Sulfides

Sulfides (172) in which Rj = alkyl can be obtained also by direct alkylation of the 2-mercaptothiazoles either in alcaline medium (156, 597) or by phase-transfer catalysis in better yield (824). 

With the less reactive phenacylchloride, 4-phenyl-2-mercaptothiazole was obtained in quantitative yield (289, 292) either in alcoholic or aqueous solution. 

The synthesis of sulfides (172) can be carried out by condensing 2-mercaptothiazoles and the required o-bromo compounds in basic solution at room temperature (488). 

Probably the mechanism of this reaction is similar to that proposed for the Hantzsch s synthesis and discussed in Section II.l.D, 

The first step of the reaction involves the formation of the S-C bond with the elimination of a molecule of ammonium salt. The fact that it has been possible to isolate the acyclic intermediate (176), R = Me or Ph, would confirm this hypothesis, particularly when the reaction is carried out for a short time in the cold in ethereal solution (27, 82). These intermediates (176) can be cyclized quantitatively on standing or on being treated by hydrochloric acid. However, no evidence has been advanced concerning their structures. 

---

Thus reduction of the 5-thiocyanato group of 151 by zinc (333, 360, 361) or aqueous sodium sulfide (348. 362), hydrolysis of the thiouronium group (7, 363, 364), and deacetylation of the 5-acetylthiothiazole with cold piperidine (365) have been performed to yield the 5-mercapto-thiazole (Scheme 78). It must be pointed out that depending on the experimental conditions, bis(5-thiazolyl(sulfide may be observed as a byproduct (363, 365). Thus 5-amino-4-methylthiazole (152) treated with... 

Reaction witii Salts and Esters of Ditiiiocarbamic Add 2 Mercaptothiazole Derivatives and 2-Thiazolyl Sulfides... 

Other sulfur compounds such as thiourea, ammonium dithiocarbamate, or hydrogen sulfide also lead to 2-mercaptothiazoles. Thus thiourea has been used in the syntheses of 4,5-dimethyl (369) and 4-aryl-2-mercapto-thiazoles (Table 11-30) (519). The reactions were carried out by condensing the ia -thiocyanatoketones with thiourea in alcohol and water acidified with hydrochloric acid. By this procedure, 4-aryl-2-mercaptothiazoles were obtained in yields of 40 to 80% with bis-(4-aryl-2-thiazolyl) sulfides as by-products (519). These latter products (194) have also been observed as a result of the action of thiourea on 2-chloro-4-arylthiazole under the same experimental conditions. They can be separated from 2-mercaptothiazoles because of their different degrees of solubility in sodium hydroxide solution at 5%. In this medium bis-(4-phenyl-2-thiazolyl)sulfide is... 

The higher reactivity of 2-halogenothiazoles with respect to halogenopyridines can be related to the different aromaticity of the two systems, less for thiazole than for pyridine, for example, the relatively stronger fixation of the tt bond in the thiazole than in the case of pyridine. As the data reported in Table V-1 (footnote a) indicates, the free thiophenol is more reactive than the thiolate anion toward the 2-halogenothiazoles. This fact should be considered when one prepares the thiazolyl sulfides. 

Thiazolyl sulfamic acids, rearrangement of sulfonic acid, 70 rearrangement to sulfonic acid, 75 by sulfonation, 75 2-Thiazolyl sulfenyl chloride, transformation to, thiazolyl disulfides. 412 2-Thiazolyl sulfide, in hydrocarbon synthesis, 406 oxidation of, with m-chloroperbenzoic acid, 415 with CrOj, 415 with Hj02,405,415 with KMn04,415 physical properties, infrared, 405 NMR, 404 pKa, 404 ultraviolet, 404 preparation of, from 2-halothiazoles and 5-Thiazolyl sulfides, bis-5-thiazolyl sulfide, oxidation of, 415 general, 418 5-(2-hydroxythiazolyl)phenyl sulfide case, 418 physical properties, 418 preparation of, 417-418 table of compounds, 493-496 uses of. 442 2-Thiazolyl sulfinic acid, decomposition of, 413 preparation of, from 2-acetamidothiazole sulfonyl chloride, 413 from A-4-thiazoline-2-thione and H, 0, 393,413 table of compounds, 472-473 5-Thiazolyl sulfinic add, preparation of,... 

Phenylthiazole-5-thiol exists in the thiol form in both polar and non-polar solvents, in contrast to the behavior of the corresponding thiazolinone. Its alkylation in alkaline medium takes place on the exocyclic sulfur atom. 5-Thiazolyl sulfides are reactive toward oxidizing agents, yielding the corresponding 5-sulfones (Scheme 149). 

H2-Thiazolyl)semicarbazides, from N-amidothiosemicaibazide and oi-halo-carbonyl compounds, 255 2-Thiazolyl sulfides, antifungal activity of,... 

The only known way to synthesize 3-substituted 6-phenyl-l,4,2-oxathiazines 8 is by ring expansion of 1,3-oxathiolinm salts 7 (see Houben-Weyl, Vol. E8a, p lOff) with azide ions (Method A), iodine/ammonia (Method B) or sulfenamides 11,12 (Method C).47 48 As intermediates, sextet structures of the nitrenium ion or nitrene type are under discussion. It is remarkable that the ring expansion obviously only incorporates the nitrogen function into the C—O bond and therefore only produces 8. 1,4,3-Oxathiazine derivatives, which could equally be formed, were not discovered.48 All three methods A C produce 1,4,2-oxathiazines 8 in yields which are moderate at best. The reaction of 2-dialkylamino-5-phenyl-l,3-oxathiolium perchlorates 7b, 7c with N, V-dimethylthiocarbamoylsulfenamide 11 yields, sometimes even as the main product, also bis(4-pheny -2-dialkylamino-5-thiazolyl) sulfides 9.48... 

I2 (or I rs, or Cl2) added in small portions to a soln. of 2-amino-4-methylthiazole and thiourea in warm distilled water, a small amount of tar filtered off, and solid NaOH added to the filtrate until the soln. is just neutral to litmus — bis- (2-amino-4-methyl-5-thiazolyl) sulfide. Y 70.9%. (F. e. s. R. G. Woodbridge 3rd, and G. Dougherty, Am. Soc. 71, 1744 (1949).)... 

The anodic fluorination of 2-thiazolyl sulfides was successfully carried out to provide the corresponding 5-fluorothiazole and 2,5,5-trifluorothiazoline derivatives [80]. 

Riyadh SM, Fuchigami T (2002) Electrolytic partial fluorination of oigamc compounds. 64. Anodic mono- and difluorination of thiazolyl sulfides. J Org Chem 67 9379-9383... 

---