2-Mercapto-4- thiazole

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 best evidence for the photolytic decomposition of mercaptans and disulfides into free radicals involves photoinitiation of polymerization of olefins. Thus, photolysis of disulfides initiates the copolymerization of butadiene and styrene,154 as well as the polymerization of styrene207 and of acrylonitrile.19 Thiophenol and other thiols promote polymerization upon ultraviolet irradiation.19 Furthermore, the exchange of RS-groups between disulfides and thiols is greatly accelerated by light. Representative examples are benzothiazolyl disulfide and 2-mercapto-thiazole,90 tolyl disulfide and p-thiocresol, and benzyl disulfide and benzylmercaptan.91 The reaction probably has a free radical mechanism. Similar exchange reactions have been observed of RS-groups of pairs of disulfides have been observed.19... 

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... 

Numerous compounds of this series exist in their tautomeric form as 2-amino(or hydroxy or mercapto)thiazoles or as substituted thiazolidines, and are dealt with under those headings. Examples of true 4-thiazolines, containing an iV-substituent in their heterocyclic ring, are less numerous, and their literature is correspondingly less extensive. 

The nucleophUic reactivity in neutral medium has been used extensively to prepare various thioethers of thiazole (122). In acidic medium, alkylation may be performed with alcohols (123, 124). An unexpected reaction encountered was the decarboxylation of 2-mercapto-4-methyl-5-thiazolecarboxyhc acid (60) when treated with butyl alcohol under acidic conditions (Scheme 27) (123). Reaction between A-4-thiazoline-2-thione... 

A-2-Thiazoline-5-thiones are generally not obtained by direct heterocyclization reactions (352). Instead, most of the reported preparations involve reactions in which the thiazole ring is already formed with the suitable mercapto precursors in the 5-position. 

The interesting reactions where a free mercapto group is linked to the nitrogen atom of the thiazole (63), after the cleavage of a fused ring, is another illustration of the additive properties of the carbocation (Scheme 40). 

Ethyl-cf-chloroacetoacetate gives 5-carbethoxy-4-methyl-2-thiazole thiol (387), while 3-chloro-2,4-pentanedione affords the 2-mercapto-4-methyl-5-thiazolylmethylketone in good yield (74%) (387). 

Similarly, ethylbromopyruvate yields ethyl-2-mercapto-4-thiazole car-boxylate (488). 

The behavior of the 2-mercapto-4-arylthiazoles in this reaction would seem to be analogous to that of the 2-mercaptobenzothiazoles (137). It appears that monosulfide compound (195) cannot be obtained from 2-chloro- and 2-mercapto-4-phenylthiazoles (given the difficulty of preparing it in this way) but rather by the action of the 2-mercapto-4-phenyl-thiazole on the intermediary, 4-phenyl-2-isothiazolyl isothiouronium chloride (194), as in Scheme 101. 

Carbon disulfide readily reacts with a-aminonitriles giving 2-mercapto-5-aminothiazoles (213), (271, 293) which can be converted to 5-aminothiazoles unsubstituted in the 2-position (Scheme 110 and Table II-34a). If this reaction is carried out in the presence of benzyl chloride in phosphorus tribromide, a 2-S-substituted thiazole derivative (214) is obtained in quantitative yield (Scheme 111), with R = hydrogen or phenyl (68, 304). 

When benzaldehyde or its substituted derivatives are added to carbon disulfide and a-aminonitrile, the corresponding 2-mercapto-5-(p-R-benzylideneamino)thiazoles (215), R = hydrogen atom or a propenyl or phenyl group and Ar = aryl, are obtained (Scheme 112) (393, 442, 694). Yields ranged from 40 to 60% (Table II-34b). 

VI. THIAZOLES FROM IVITRILES AND a-MERCAPTO-KETONES OR ACIDS 2,4-DISUBSTITUTED AND 4-HYDROXYTHIAZOLE DERIVATIVES... 

This method has mainly been used to prepare thiazoles nonsubstituted in the 2-position and involves the replacement of a functional substituent (amino, halo, mercapto, hydroxy, or carboxy) by a hydrogen. In this way the often delicate cyclization of thioformamide can be avoided. 

Another possible route to 2-unsubstituted thiazoles is replacement of a mercapto group by a hydrogen. Various methods have been used hydrogen peroxide in acid medium (17-19) dilute nitric acid (17), and metallic catalysts (20-22). 

A large number of variously 2-, 4-, and 5-substituted thiazoles with alkyl, aryl, hydroxy, methylthio, mercapto, halo, and nitro groups have been analyzed by thin-layer chromatography on silica and alumina by the Stahl s technique (167, 170, 172). Among the many systems recommended for the elution of these compounds are the following ... 

Thiazol-3-ium, 3-ethyl-2-[A -(3 -ethyl-2 -thiazolylidene)-3-ylidene-1 -pro pen]-1 -yl-visible, 1, 345 (B-76MI11201) Thiazolo[2,3-a]isoquinolinium, anhydro-3-(4-bromophenyl)-2-mercapto-X-ray, 6, 669 (67JCS(B)1117)... 

Thiazole, 5-amino-4-ethoxycarbonyl-2-methyl-synthesis, 6, 306 Thiazole, 2-amino-4-(2 -furyl)-bromination, 6, 256 Thiazole, 2-amino-4-hydroxy-synthesis, 6, 296 Thiazole, 5-amino-2-hydroxy-synthesis, 6, 301 Thiazole, 5-amino-2-mercapto-synthesis, 6, 301 Thiazole, 2-amino-4-methyl-alkylation, 6, 256 synthesis, 6, 300 Thiazole, 2-amino-5-nitro-antiparasitic activity, 1, 180... 

Grignard reagents from, 5, 106 reactions, 5, 104 6, 274, 292 reactivity, 6, 292 synthesis, 6, 297 Thiazoles, imino-reactivity, 6, 250 Thiazoles, isopropenyl-radical polymerization, 6, 278 Thiazoles, mercapto-industrial uses, 6, 330 reactions, 5, 102 synthesis, 6, 298-299 tautomerism, 6, 247, 248, 269, 289 Thiazoles, methyl-... 

A. 2-Allylthio-2-thiazoline [Thiazole, 4,5-dihydro-2-(2-propenyltliio)-]. A solution of 11.9 g. (0.100 mole) of 2-mercapto-2-thiazoline [2-Thiazoli-dinethione] (Note 1) in 00 ml. of tetrahydrofuran is prepared in a 200-ml., one-necked, round-bottomed flask fitted with a 25-ml.,... 

Thiazoline, 2-ethylthio [Thiazole, 2-(ethylthio)-4,5-dihydro-], 82 2 Thiazohne, 2-mercapto [2 Thiazohdine-thione], 77... 

Thiazolidine, 2,5-Dihydro- 1,3-thiazole, Tetrahydro-l,3-thiazine und 5,6-Dihydro- 1,3-thiazine werden durch Lithiumalanat6,7 und meist auch durch Natriumboranat7 zu den (w-Mercapto-aminen aufgespalten. 1,3-Thiazolidine lassen sich mit einem Lithi-umalanat-OberschuB ahnlich den 4,5-Dihydro-1,3-oxathiolanen zu Athylaminen wei-terreduzieren7,8 ... 

Hexamethyiene tetramine Mercapto benzo thiazole Ortfio-toiuidine Para-loluidine... 

Hexamethylene tetramine Mercapto benzo thiazole Ortho-toluidine Para-toluidine... 

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