Imidazole N-oxides

Reaction of trisubstituted imidazole N-oxides such as l,4,5-trimethylimidazole-3-oxide 930 with 18/NEt3 in CH2CI2 at 0-5 °C affords the l,4,5-trimethyl-2-cyano-... 

Oxidative Fluorination of Nitrones to a-Fluorosubstituted Nitroxyl Radicals Formation of nitroxyl radicals by the radical cation route was observed in reactions of various nitrones with xenon difluoride in dry methylene chloride (520, 523). In this reaction, more than 40 nitrones, including 4H -imidazole N,N -dioxides (219), 4H -imidazole TV-oxides (223) and (224), 2H -imidazole N -oxides (225), 2H -imidazole TV,TV-dioxides (226), 3,3,5,5-tetramethylpyrroline N -oxide (TMPO), derivatives of 3-imidazoline-3-oxides (231) and (232), have been examined. ESR spectra of nitroxyl radicals containing one or two fluorine atoms at a-C have been registered (Scheme 2.108) (523). In the case of... 

H3C-CH-COOH H3C h3c 4N HC1 Ruckfl. 1-[ l- (2-Benzimidazolyl) -cthy )-4,5-dimethyl-imidazol-N -oxid 62 194-198 249... 

Imidazolones, particularly 2-imidazolones, give the corresponding chloro derivatives when heated with phosphoryl chloride, especially with copper(I) chloride as catalyst [76MI1 80AJC1545 90EGP3828208]. The same reagents convert imidazole N-oxides into 2-chloroimidazoles [75JCS(P1)275]. 

Sulfotransferase activity is not restricted to minoxidil. The ability of other pyrimidine-, as well as pyridine-, triazine- and imidazole N-oxides to serve as substrates was investigated using soluble liver preparation and PAPS. The variety of structures studied indicated that heteroaromatic N-oxides are generally metabolized by sulfotransferases183. Presumably, all of the heterocycles tested were conjugated via their N-oxide oxygens. 

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. 

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. 

Since the direct Af-oxidation of imidazoles has not yet been achieved, the synthetic methods available start with acyclic precursors. In consequence the range of compounds is not extensive, and their reactivity is not well known as yet. Since most of the published chemistry relates to the reactivity of the oxide function, it has been considered preferable to discuss all of the reactions of imidazole N-oxides in Section 4.07.3.9.8. 

Sodium borohydride converts 4//-imidazole N-oxides into 1-hydroxy-imidazoline or -imidazolidine derivatives. Under the same conditions 1,3-dioxides form 1,3-dihydroxy-imidazolidines (76CHE1280). 

When l-hydroxy-3-imidazoline 3-oxides (263) are treated with HCl they dehydrate forming imidazole 3-oxides (Scheme 153) (73CHE1175). Reduction of 4//-imidazole N-oxides with borohydride leads to either 1-hydroxy-imidazolines or -imidazolidines, depending on the position of the oxide function. Under the same conditions 4//-imidazole 1,3-dioxides give 1,3-dihydroxyimidazolidines (76CHE1280). The 4iT-imidazole AT-oxides are prepared by heating 5,5-disubstituted l-acyloxy-3-imidazoline 3-oxides in vacuo. 

Imidazole N-oxides are accessible by reaction of an equimolar mixture of an a-diketone and an aldoxime or aldehyde in the presence of hydroxyl-amine. ... 

The oxide function can be removed using phosphorus trichloride, or phosphorus oxychloride, by reduction with hydrogen and Raney nickel" with sodium borohydride, and with hexachlorodisilane in chloroform. The reduction of 4H-imidazole N-oxides with borohydride leads to the 1-hydroxyimidazoline or imidazolidine derivatives under the same conditions 4if-imidazole JV,N -dioxides give 1,3-dihydroxy-imidazolidines. ... 

Although imidazole N-oxides cannot be prepared by direct oxidation of the heterocycles, a number have been prepared by cyclization methods (Section II,C and F) and their properties have been studied (Section IV,B and C). 

The photochemistry of five- and seven-membered heterocycHc N-oxides is most often related to that observed with nitrones. Thus, rearrangement to bicychc oxaziridines has been documented in a number of cases. Both with 2H- and with 4H-imidazole N-oxides, rearrangement to the corresponding oxaziridines has been reported. The N,N-dioxide of the latter heterocycle (19, n = 1, see Equation 99.15) undergoes two consecutive photorearrangements to give the cis- and trans-isomers of the tricyclic derivative. 

Gainsford, G.J. and Woolhouse, A.D., Facile photoisomerization of 2H-imidazole N-oxides to 1,3-diaza-6-oxabicyclo[3.1.0]hex-3-enes and synthesis of a l,3-diaza-4,7dioxatricyclo[4-l-0.0]heptane, J. Heterocyclic Chem., 29, 803, 1992. 

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