Replacement of a Mercapto Group

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). 

The dye C.I. Solubilised Sulphur Red 11 [90218-69-2] (25) contains neither thiolate groups nor their precursors. It is prepared by treating perylenetetracarboxylic dianhydride with l,4-diaminobenzene-2-sulfonic acid, then with cyanuric chloride and with NH3. It is not known whether the chlorine of the monochloro-triazine groups of the precursor is replaced by a mercapto group in dyeing. 

If the hydroxy group of a 2-amino alcohol is replaced by a mercapto group (XCIX) the reaction with carbon disulfide yields thiazolidine-2-thiones (C) with liberation of hydrogen sulfide. This method though is practically never used since thiazolidine-2-thiones are more simply obtained from 2-halo amines (see further under Section IV.l) which are themselves starting materials for the 2-amine thiols. 

Thiamine anhydride (77) is a useful source of sulphur analogues of thiamine. Thus, it reacts with thioacetic acid to give the thiazolinethione (78), which on successive desulphurization by the action of hydrogen peroxide and treatment with barium chloride affords acetylthioethylthiamine (79) hydrolysis finally produces mercaptoethylthiamine (80), the sulphur analogue of thiamine. This is convertible into further derivatives, particularly by replacement of the mercapto-group of the 5-side-chain by amino-, sul-phenyl-, sulphinyl-, and sulphonyl-residues [e.g. (81), (82)]. ... 

This preparation describes a convenient and general method of synthesis of substituted pyrimidines from compounds containing a /3-dicarbonyl group, either intact or as the corresponding ketal. The usefulness of the 2-mercaptopyrimidines is enhanced by the ease of removal of the mercapto group by desulfurization 9 or oxidation 10 and its replacement by other functional groups.1 ... 

The replacement of an amino group by a mercapto group on an aromatic nucleus is effected by treating the diazotized amine with potassium ethyl xanthate and hydrolyzing the resulting aryl ethyl xanthate (Leuckart). Yields of 40-80% are reported for thiophenols containing methyl, halo, and methoxyl groups. Potassium ethyl xanthate is readily prepared from alcoholic potassium hydroxide and carbon disulfide. ... 

Since this procedure can be used to replace any sulfur atom in a molecule by a hydrogen, it is not surprising that it has many synthetic uses. Thioketals are converted to the hydrocarbons providing a good method for the removal of a carbonyl group in neutral medium. 57.167 Unsaturated thioketals are desulfurized over deactivated Raney nickel without saturation of the double bond (Eqn. 20.67). Mercapto pyrimidines have been desulfurized in very good yields and sulfonamides converted to amides. 70 Thioethers can be cleaved in preference to benzyl ethers if deactivated Raney nickel is used. 

Dunbrook and Zimmermann 113) report still higher yields, even with short reaction times, when sodium polysulfide and carbon disulfide are used (method C ). The essential appears to be the replacement of the chlorine atom by a mercapto group and the reduction of the nitro group to an amino group, followed by ring closure of the resulting o-aminothiophenol with carbon disulfide to the benzothiazoline-2-thione (method A). 

One nitro group of 0-dinitrobenzene and its derivatives is reactive and can be replaced by a mercapto, alkylthio, or sulfo group under the influence of sodium sulfide, sodium thiolates, or sodium sulfite, respectively. For preparative purposes this reaction is, however, restricted to a few examples. o-Dinitro-benzene and sodium sulfide give bis-(0-nitrophenyl) sulfide,492 and trinitro-anisole gives the bis(methoxydinitrophenyl) sulfide.493... 

Thiazolo[4,5-b]pyrazines. 2-Amino-3,5-dibromopyrazine refluxed 3 hrs. with a soln. obtained by saturating KOH in methanol with HgS 2-amino-3-mercapto-5-bromopyrazine (Y 96%), 7 g. refluxed 3.5 hrs. with acetic anhydride 6 g. 2-methyl-6-bromothiazolo[4,5-b]pyrazine refluxed 3.5 hrs. with a soln. of Na in methanol -> 2-methyl-6-methoxythiazolo [4,5-b] pyrazine (Y 78%) refluxed 2 hrs. with a soln. of NaOH in water-methanol 2-amino-3-mercapto-5-methoxy-pyrazine (Y 92%).—The above method circumvents the influence of the amino group, which ordinarily hinders replacement of a halogen atom in the 5-position. G. Palamidessi and L. Bernardi, G. 91, 1438 (1961). 

The versatility of pyrimidine substituted chloroquinazolines as intermediates is due to the ready replacement of the halogen atoms by hydrogen, alkyl, alkoxyl, amino, and mercapto groups (see Section VI, A). 

An intramolecular 8 Ar2 mechanism (19) is possible in the replacement of 0X0 substituents with chloro or mercapto groups by means of phosphorus oxychloride or pentasulfide, respectively, via the intermediates shown. In the former, an intermolecular mechanism (20) is perhaps more likely. Frequently a base is not added in such reactions. 

Alkylthio, arylthio, and thioxo. The thioxo group in pyrimidine-2,4-dithione can be displaced by amines, ammonia, and amine acetates, and this amination is specific for the 4-position in pyrimidines and quinazolines. 2-Substitution fails even when a 5-substituent (cf. 134) sterically prevents reaction of a secondary amine at the 4-position. Acid hydrolysis of pyrimidine-2,4-dithione is selective at the 4-position. 2-Amination of 2-thiobarbituric acid and its /S-methyl derivative has been reported. Under more basic conditions, anionization of thioxo compounds decreases the reactivity 2-thiouracil is less reactive toward hot alkali than is the iS-methyl analog. Hydrazine has been reported to replace (95°, 6 hr, 65% 3deld) the 2-thioxo group in 5-hexyl-6-methyl-2-thiouracil. Ortho and para mercapto- or thio- azines are actually in the thione form. ... 

---