N-hydroxyimidazoles

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

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. 

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... 

The N-hydroxy structure (26) was preferred123 to an iV-oxide representation on account of the amphoteric nature of the product and because the derived acetate formed a well-defined hydrochloride salt. Hydrogenation of these N-hydroxyimidazoles over Raney nickel gives imidazoles in 60-94% yields.122 The reaction has been adapted for the preparation of 4-mercaptoimidazoles, using an a-ketothionamide (27) with an aldimine.124... 

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 ... 

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

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

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

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. 

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. 

One of the common properties of imidazole N-oxides is their strong association even in dilute solution, and in the solid state such association can mask distinction in the IR between NH and OH bands. Thus IR studies of such compounds in the solid state may give rise to confusing results. Careful UV studies of 1-hydroxybenzimidazoles show that with a variety of substituents (e.g. 6-nitro, 2-alkyl or 2-aryl) the hydroxy form (73) is favoured in organic solvents, and the more polar oxide form (74) in water (there is a mixture of both in aqueous ethanol). With 1-hydroxybenzimidazole the N-methyl model (75) is not sterically hindered, and the value of Kt (74173) = 12 deduced from the pK values of the models (75/76) in water should be much more reliable than that for the hydroxyimidazoles (Scheme 24). In other solvents (benzene, chloroform, acetonitrile, dioxane), UV results show that the OH form (73) predominates in 75% aqueous ethanol Kt=1. 

Decomposition of 6-nitro TP 134b proceeds quite differently in the presence of the N-nucleophile benzylamine and leads unusually to 1-hydroxyimidazole 135 (Path B) (93MC213). 

Much of the synthetic activity involving formation of the 1,5- and 2,3-bonds has centered on the preparation of hydroxyimidazoles and their N-oxides. Since direct N-oxidation of the imidazole ring has not been accomplished, ring-synthetic methods provide the only means of access to compounds of this type. While not all of the reactions described below conform strictly to the classification of this section, the methods are sufficiently similar to permit... 

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