2- Hydroxyimidazole, tautomerism

A review has highlighted the roles of zwitterions in hydroxyimidazole tautomerism, for example, an aromaticity index (7 see Section 3.02.4.2.1) of 68 points to a zwitterionic species (39) rather than the hydroxy tautomer (40) which would have an value of around 79 (Equation (4)) <94H(37)249>. Thiols generally resemble the oxy analogues. Solid state IR and Raman spectroscopy point to imidazole-2-thiol existing in the SH form in the solid <89CCC2045>. 

The prototropic tautomerism of 5-hydroxyimidazoles 115 may involve eight possible forms for N -unsubstituted and four forms for N -substituted compounds (Scheme 45). 

Little information is available on the tautomeric equilibrium of N-hydroxyimidazoles 117 and A-hydroxybenzimidazoles 118 in solution... 

Tlie oxo-thione form 241 is taken for 2-mercapto-4-hydroxyimidazoles (Scheme 83) [76AHC(S1), p. 463]. These tautomeric equilibria were clarified by the consideration of models in which some tautomeric forms were blocked. Thus, for S-alkylated 5,5-diphenyl 242 or 5-spirocyclohexyl 243 derivatives, oxo-thiol forms are the major tautomers [73T3565 76AHC(S1), p. 463]. 

Two tautomeric equilibria have been considered for substituted imidazoles, that between 2-imidazolone 3 and its 2-hydroxyimidazole tautomer 4 [268] and also that between the 1H and 3H tautomers of 4-nitroimidazole, 6 and 5, respectively [269, 270], Karelson et al. used the D02 model with a spherical cavity of 2.5 A radius and found 2-imidazolone to be better solvated than its tautomer by 7.7 kcal/mol at the AMI level. [The asterisk in D02 indicates that the reaction field... 

The aromatic imidazole N-oxides have structure 245. The parent compound 246 displays tautomerism between the N-oxide tautomer 246 and the 1-hydroximidazole tautomer 247 (Scheme 68). 1-Hydroxyimidazole 247 and substituted 1 -hyd roxyimidazoIes 249 belong to a separate group of compounds, which is not discussed in the present review. 

As discussed in the General Chapter (Section 4.01.5), imidazoles with potential hydroxy, thiol and amino substituents can exist in a variety of tautomeric forms. In contrast to the hydroxypyrazoles which have been studied in detail, comparatively little is known about the corresponding 1,3-diazoles. Many of the imidazoles are not easily accessible synthetically, and they may not be particularly stable e.g. 4-hydroxyimidazoles). Amino derivatives... 

Many workers in recent years have been interested in the tautomeric equilibria pertaining to oxygenated imidazoles such as imidazolones, " " N-hydroxyimidazoles, and imidazole iV-oxides. The earlier results have been critically summarized. In the solid state l,2-dimethyl-5-phenylimidazol-4-one exists in the OH form, but insolubility prevented studies in solution. Theoretically l-methylimidazol-5-ones can exist in the forms 93-96 shown in Eq. (22). French workers ... 

Theoretical study of the 2-hydroxyimidazole 2-imidazolone tautomerism predicts that in solution the 0x0 form should exist (as observed experimentally). The dipole moment of the 0x0 tautomer is substantially altered in solution compared with that of the hydroxy form <90JCS(P2)195>. 

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