2-amino-4-hydroxythiazoles

The a-halogenated acids or their esters (105) also react with thiourea to give 2-amino-4-hydroxythiazoles (106a) or their 2-amino-4-thiazolone (106b) (1, 247, 254, 530) or 2-imino-4-oxathia2olidine (106c) tautomers (Scheme 47). 

Thus with ethyl a-chloroacetate (105), R = H, X=C1, Robba and Moreau (530) obtained the 2-amino-4-hydroxythiazole (106), R = H, known as pseudothiohydantoine. 

In contrast to iV-disubstituted 3-hydroxyanilines which react with Vilsmeier reagent to give AWisubstituted salicylaldehydes, their heteroanalogous iV-disubstituted 2-amino-4-hydroxythiazoles (60) react with Vilsmeier reagent to give iV-disubstituted 2-amino-4-chlorothiazole-5-aldehydes (61) <96JPR51>. 

The a-halo acids and their esters also react with thiourea to give 2-amino-4-hydroxythiazoles. Pseudothiohydantoin (237) is thus obtained by condensation of ethyl a -chloroacetate with thiourea and in the course of the reaction it is possible to isolate the acyclic intermediate (236 Scheme 169). Similarly 2,4-diaminothiazole hydrochloride is readily prepared by the reaction of thiourea with chloroacetonitrile in warm alcoholic solution (Scheme 170). 

Pseudothiohydantoine, as acyclic intermediate, in reaction of o-halogeno acids or esters with thiourea, 232. See also 2-Amino-4-hydroxythiazole Pyridazines (4,7-dioxo-4,5,6,7-tetrahydro-thiazolo[4,5d]), preparation of, 206 Pyridine, electronic structure, 36, 39, 46 ultraviolet absorption, 47 thiazolylation of, 373 2-(4-Pyridyl)-4-carboxyethylthiazoie, from thioisonicotinamide and ethyl bromopyruvate, 198... 

Thiourea reacts with a-halocarbonyl compounds to produce 2-aminothiazoles. 2-Amino-4-hydroxythiazoles 6 are formed with a-halocarboxylic acids ... 

Substituted 5-hydroxythiazoles (267b), Rj = alkylmercapto, acyl-amino, and sec-amino, are prepared by cydization of N-thioacyl-amino acids (266) with phosphorus tribromide or acetic anhydride (Scheme 137) (317, 350). i en the cydization of 266, R2 = H, is carried out with acetic anhydride in the presence of benzaldehyde (317, 325) or ethylformate (317), the benzylidene (268), R2=Ph, Rj = SR or CH2Ph, or 4-ethoxymethylene (268), Rj = SR and R2 = OEt, derivative is obtained directly (Scheme 138). 

Uses, aminothiazoles derivatives, 132-172 hydroxythiazole derivatives, 438-442 mercaptothiazole derivatives, 438-442 UV spectra, 21 of alkylaminothiazoles. 38 and amino-imino equilibrium, 19, 20 and charge transfer, 21 of iminothiazolines, 38 and PPP calculations, 21 and potentiometric measurements, 21 representative data, 22 of Schiff bases, 41 and solvent effects, 21 and substituent effects, 22 of sulfathiazoles, 20 -of sulfonamidothiazoles, 116 of A-2-thiazoline-4-one, 422 pKa determination, 423 of A-4-thiazoline-2-one, in relation with protomerism, 387 representative data, 389 of A-4-thiazoline-2-thiones, 380. 381 in relation with protomerism. 378 of thiazolylcarbamates, 97 of thiazolyl-2-oxides, 409 of thiazolyl-4-oxides, 426 of 2-thiazolylthioethers, 404 of thiazolylthioureas, 94, 96 of thiazolylureas, 93... 

This method, initiated by Marchesini in 1893 (i893G(24)65) (Scheme 177), consists of the condensation of an a-halocarbonyl compound with ammonium thiocarbamate (244 R2 = NH4) or its esters (244 R2 = alkyl). The reaction is carried out at low temperature in aqueous medium and then allowed to stand overnight. 2-Hydroxythiazoles (244 R2 = H) give 2-chlorothiazole derivatives almost quantitatively upon treatment with phosphorus oxychloride. This constitutes a convenient synthetic method for these compounds when the conversion of 2-amino- into 2-chloro-thiazole fails. 

By condensing carbon oxysulfide with a-aminonitriles, the corresponding 5-amino-2-hydroxythiazoles can be obtained (Scheme 194). In the presence of benzaldehyde the reaction leads to 5-benzylideneaminothiazole derivatives in good yields. 

Synthesis. - Hantzsch s Synthesis (Type A S—C—N + C-C) From thioureas. Starting from thioureas, the following compounds have been obtained 2-amino-4-(4-benzyloxyphenyl)thiazoles, 2-(2-amino-5-hydroxythiazol-4-yl)-1 -(4-chloro-3-methylphenyl)ethanone, 2-benzylidenehydrazino-4-( 1,5 -di-... 

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