Hydroxyimidazoles

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]. 

Chemical evidence for the structure of imidazol-4-ones has been summarized,although rather different conclusions would now be drawm from this evidence. For example, in the light of present knowledge, the ease with which imidazol-4-ones react with diazonium salts suggests that an appreciable amount of the 4-hydroxyimidazole exists... 

Scheme 14). The diversity of the collection of imidazoles prepared was relatively high, and yields ranged from 17 to 83%. It is interesting to observe that the intermediate N-hydroxyimidazole 46 was obtained when the reaction was carried out at temperature lower than 200 °C. 

See l-Methoxy-3,4,5-trimethylpyrazole A-oxide, also 1-Hydroxyimidazole N-oxide... 

A closely related protocol for the synthesis of imidazoles was independently investigated by Sparks and Combs (Scheme 6.199) [362]. Here, the authors employed readily available unsymmetrical keto-oximes as building blocks, initially leading to N-hydroxyimidazoles. Diaryl keto-oximes were condensed with various aldehydes (1.1 equivalents) in the presence of 4 equivalents of ammonium acetate under microwave conditions at 160 °C. In this way, the N-hydroxyimidazoles were formed... 

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... 

Hydroxyimidazoll,2-alpyrimidine-6-carboxvlates 51BSB69 59JO-C779 82IJC(B)1030... 

Hydroxyimidazole-2-carboxaldoxime 3-oxide, 1477 1 -Hydroxyimidazole N-oxide, 1134 Hydroxylamine, 4498 /V-Hvdroxvsuccinimidc. 1469... 

Translocation of the oxygen with C-T of acyclovir gave analogs of potent biological activity. Their synthesis was achieved by two main methods. The first includes alkylation of the hydroxyimidazole derivative 990 with 3-... 

Oximes can be also used for the imidazole ring synthesis. Thus, reaction of a-amino-oximes 122 and orthoesters leads to imidazole Af-oxides 123 (equation 53) . Interaction of a-ketooxime 124 with triazinanes also afforded imidazole Af-oxides 125 in good yields (equation 54) . Similarly, a-ketooximes in the system NH3/H20/aromatic aldehyde afforded trisubstituted 1-hydroxyimidazoles . ... 

Hydroxy-2-hydroxylamino-1,3,4-triazole, 0813 l-Hydroxyimidazole-2-carboxaldoxime 3-oxide, 1473 1 -Hydroxyimidazole IV- oxide, 1131... 

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. 

The 3-hydroxyimidazole 1-oxides 267 should be handled with care because they undergo violent decomposition upon heating (1971RZC1747, 1998HCA1585). At room temperature imidazole 1-oxides 228 are usually stable, crystalline, polar, and hygroscopic compounds. An exception is imidazole 1-oxides devoid of substituents at the 2-position, which may rearrange to... 

Substituted imidazole 1-oxides 228 can be prepared by N-oxidation of imidazoles 248, by N-alkylation of 1-hydroxyimidazoles 249, or by cycliza-tion using suitable starting materials derived from a 1,2-dicarbonyl compound, an aldehyde, an amine, and hydroxyamine. The substituents at the three first starting materials are transferred to the product and make control over the substituents in the imidazole 1-oxide 228 possible depending on the protocol used by the synthesis. The synthesis of 3-hydroxyimidazole 1-oxides is presented in Section 3.1.6. 

At-Alkylation of 1-hydroxyimidazoles 249 produces 3-substituted imidazole 1-oxides 228 (R=Aik) in low yields due to competing O-alkylation and dialkylation leading to 1-alkoxyimidazoles 250 and l-alkyl-3-alkyloxy-imidazolium salts 251, respectively (1970ZC211,1990S795) (Scheme 70). 

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