Thiazole hydroxy-, tautomeric forms

Thiazoles and their derivatives bearing amino, hydroxy, or thio groups in the 2-position can exist in at least two tautomeric forms,... 

Substituted thiazoles at C-2 or C-4 with hydroxy, thio, and amino groups can be represented by five tautomeric forms (26a-e) (Scheme 1). However, form (26e) has never been observed <85JPR25l>. The aminothiazoles exist predominantly in the amino form when the substituent is in position two (26b, Z = NH). On the other hand, when the substituent is in position four the amino form is preferred, although there are exceptions to this rule (for instance, in the case Y = Z = NHCOMe). The hydroxy and thio derivatives predominantly exist in the oxo and thioxo forms (26a, Y, Z = O, S). The main evidence of these arguments came from the C NMR spectra of the thioxo derivatives and from the IR spectra of the oxo and amino derivatives. 

Thioglycolic acid reacts with active methylene compounds such as (288) to give 4-hydroxy thiazoles (289). The spectral analysis shows that the predominant tautomeric form is (289b) both in solid state and DMSO solution (Scheme 73) <92T9295>. 

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 4- and 5-hydroxy-imidazoles, -oxazoles and -thiazoles (499, 501) and 4-hydroxy-pyrazoles, -isoxazoles and -isothiazoles (503) cannot tautomerize to an aromatic carbonyl form. However, tautomerism similar to that which occurs in hydroxy-furans, -thiophenes and -pyrroles is possible (499 500 503 504 501 502), as well as a zwitterionic... 

Investigations on the tautomerism of fused heterocyclic moieties favor the lactam form of the imidazole substructure of 16 (65CPB473) and the thiolactam tautomer in thiazoles 192 and 197 [62BCJ1998 64BCJ1526 95PS(101)167], but the hydroxy form in pyrazole 183 [82IJC(B)765]. 

Amino-4-aryl-thiazoles give Meisenheimer complexes with 2,4,6-trinitro-chlorobenzene. The tautomeric properties of thiazoles continue to attract attention. Unlike most 4-hydroxy-thiazoles, which prefer to exist in their keto-forms, 4-hydroxy-2-methyl-5-phenylthiazole exists as a stable enol. The spectroscopic properties of the meso-ionic thiazole (12 = Me, R = Ph, R = / -ClC H4),... 

Recently, however, there has been increased interest in N-oxides for the generation of hydroxyl radicals in aqueous solution. This process has been reported for some nitrated N-oxides but is most often observed for tautomeric N-oxides, where the N-hydroxy form is significant. " "" The main application is in photobiology, as specific sources of hydroxyl radicals for DNA damage, both strand break and base modifications. N-Hydroxy-2-pyridone and 2-pyridinethione, - N-hydroxy-4-(4-chlorophenyl)thiazole-2(3H)-thione, " and pyrimido[5,4-g ]pteridinetetraone N-oxide (for which the path followed depends on conditions) " and related N-oxides " have been used for this purpose. 

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