Imidazole JV-oxides

The mass spectrum of I-methyl-4-nitroimidazole-5-carboxylic acid amide shows the elimination of water by an electron impact as distinct from the usual thermal process. In l,4,5-trimethylimidazole-2-carboxylic acid the principal loss is that of CO2. Subsequent loss of O, OH, and HCN was also observed (Schofield et al., p. 173). Ferguson and Schofield (pp. 172,173) have reported considerable data for imidazole JV-oxides. Thus 1-methoxy-4,5-dimethyl-2-phenylimidazole (which loses OCH3 and CH3CN from the fragment m/e 171) is readily distinguished from l,4,5-trimethyl-2-phenyl-imidazole 3-oxide (loss of O and OH). The spectra of 1-benzylimidazoles are dominated by the tropylium ion. ... 

Although imidazole JV-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). 

Adaptation of similar functionality to the synthesis of imidazole JV-oxides is illustrated by the fluoride ion-promoted cyclization of the trimethylsilyl ether of the oxime (30) derived from l-(dichloroacetylphenyl)aminopropanone (Scheme 15) (80AHC(27)24l). 

Reaction of oc-aminooximes or a-dioximes with aldehydes leading to imidazole JV-oxides will be discussed in Section II,F since all of these reactions have a common basis. The widely employed reaction of an a-diamine with an alcohol, aldehyde, or carboxylic acid has been restricted mainly to the synthesis of benzimidazoles. " ... 

Many workers in recent years have been interested in the tautomeric equilibria pertaining to oxygenated imidazoles such as imidazolones, - " N-hydroxyimidazoles, and imidazole JV-oxides. - The earlier results have been critically summarized. In the solid state l -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-% shown in Eq. (22). French workers ... 

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. ... 

Dry hydrogen chloride induces ring closure of PhCH=NC(CN)=C(R)SMe to chloroimidazoles, and iV-(l-cyanoalkyl)alkylideneamine JV-oxides (26) can be converted by way of nucleophilic attack by thiophenol into imidazoles substituted at C-5 by thio-phenoxy (Scheme 13). This latter reaction is accelerated by small amounts of piperidine, but inhibited by temperatures above the melting point of the Af-oxide. The action of cyanide ion on similar nitrones gives cyanoimines which cyclize to imidazoles in 40-90% yield (80JCS(P1)244>. 

Pyrazine JV-oxides and 2,3-dihydropyrazines also rearrange photochem-ically into imidazoles. From 2,5-disubstituted pyrazine 1-oxides (73) two products, 2-acyl(or aroyl) 4-substituted imidazole (74) and 2,4-disubstituted imidazole (75), result.The reaction (Scheme 16) presumably takes place through two isomeric oxaziridine derivatives. 

Imidazole, 1 -hydroxy-2,4,5-triphenyl-3-oxides reactions, 5, 455 Imidazole, iodo-nitrodehalogenation, 5, 396-397 Imidazole, 1-iodo-reactions, 5, 454 stability, 5, 110 Imidazole, 2-iodo-synthesis, 5, 401 Imidazole, JV-iodo-, 5, 393 reactions, 5, 454 Imidazole, 4-iodo-5-methyl-iodination, 5, 400 Imidazole, 2-isopropyl-4-nitro-N-nitration, 5, 351 Imidazole, 2-lithio-reactions, 5, 106, 448 Imidazole, 2-mercapto-l-methyl-as antithyroid drug, 1, 171 mass spectra, 5, 358 Imidazole, I-methoxymethyl-acylation, 5, 402 Imidazole, 5-methoxy-l-methyl-reactions... 

Anodic oxidation of JV,iV-disubstituted trifluoroethanimidamide 45 in dry and in aqueous acetonitrile gave the imidazole 46 and quinoneimine 47 as the reaction products (Scheme 24). The constant current electrolysis on a glassy carbon anode and a platinum cathode was performed in an undivided cell [74]. 

Amino-5-(JV-hydroxyamidino)imidazole (190), refluxed for 1 hr with triethyl orthoformate and dimethylformamide, gave an excellent yield of 6-aminopurine 1-oxide. The same starting materials produced 6-amino-2-thioxopurine 1-oxide in good yield when set aside with carbon disulfide and pyridine in methanol for 5 days at 25°C.363... 

Imidazole, benzimidazole, and benzotriazole give N-phenyl derivatives in low yield with benzyne ° l-methylbenzotriazole understandably fails to react. In contrast, 2-methylbenzotriazole reacts with benzyne (from oxidation of 9 with lead tetraacetate) to give 1-phenylbenzotriazole (112) (22%). The mechanism suggested to account for incorporation of benzyne and oxidative removal of the JV-methyl group is outlined in Scheme 13 formaldehyde may be further oxidized under these conditions. 2-Benzylbenzotriazole and benzyne under the same conditions afforded 112 and benzoic add. When benzyne was generated from 4 instead, it reacted with 2-methylbenzotriazole to give phenazine (2%) and no 112. ... 

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