2,4,5-Triarylimidazoles

Oxidation of azole anions can give neutral azole radicals which could, in principle, be tt (139) or a- (140) in nature. ESR spectra indicate structure (141 hyperfine splittings in G) for imidazolyl radicals, but both tt- and cr-character have been observed for pyrazolyl radicals. Tetrazolyl radicals (142 4 143) are also well known (79AHC(25)205). Oxidation of 2,4,5-triarylimidazole anions with bromine gives l,l -diimidazolyls (144) which are in equilibrium with the dissociated free radical (145) (70AHQ 12)103). 

This transformation can also be carried out under solvent-free conditions in a domestic oven using acidic alumina and ammoniiun acetate, with or without a primary amine, to give 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazoles, respectively (Scheme 15A) [69]. The automated microwave-assisted synthesis of a library of 2,4,5-triarylimidazoles from the corresponding keto-oxime has been carried out by irradiation at 200 ° C in acetic acid in the presence of ammonium acetate (Scheme 15B) [70]. Under these conditions, thermally induced in situ N - O reduction occurs upon microwave irradiation, to give a diverse set of trisubstituted imidazoles in moderate yield. Parallel synthesis of a 24-membered library of substituted 4(5)-sulfanyl-lff-imidazoles 40 has been achieved by adding an alkyl bromide and base to the reaction of a 2-oxo-thioacetamide, aldehyde and ammonium acetate (Scheme 15C) [71]. Under microwave-assisted conditions, library generation time was dramatically re-... 

The anodic oxidation of 2,4,5-triarylimidazole was studied in aprotic solvents.291-295 The 2,4,5-triarylimidazole anions undergo a one-electron oxidation, forming dimeric bis-(2,4,5-triarylimidazolyls).294 The isomeric bis imidazolyls consist of imidazole and isoimidazole systems. The dimerization is a result of a nucleophilic attack of 2,4,5-triarylimidazole anions on the electrochemically generated 2,4,5-triarylimidazolium cations. 

Acylamino ketones on heating with ammonium acetate are converted into imidazoles. 2,4,5-Triarylimidazoles 235 were prepared in this way from the amides 234 (Scheme 113) <1973CB2415>, and numerous variations are possible for this reaction. 

SheUce, K., Kakade, G., Shingate, B., and Shingare, M. 2008. Microwave-induced one-pot synthesis of 2,4,5-triarylimidazoles using glyoxylic acid as a catalyst under solvent-free conditions. RASAYAN Journal of Chemistry, 1 489-94. 

UV spectroscopy has been applied to studies of 2,4,5-triarylimidazole radicals, imi-dazolones and various thioimidazoles. In addition, the rates of hydrolysis, alcoholysis and aminolysis of imidazolides such as 1-acetylimidazole can be determined readily since such azolides show characteristic intense absorptions at wavelengths longer than those of the imidazole products. In the C-acyl- and C-aroyl-imidazoles, those which have the carbonyl group attached at C-2 exhibit a bathochromic shift of about 20 nm, while in m- and p-substituted 2-aroylimidazoles intense absorptions (log,o e 3.5-4.3) appear in the 295-309 nm region, with slightly less intense peaks at about 233-266 nm (74CRV279). 

Reactions of the sodium salts of 2,4,5-triarylimidazoles with bromine and oxidations of A -hydroxybenzimidazoles to cyclic nitroxyls have been discussed elsewhere (Section 4.02.1.4.11). 

Treatment of 4//-l,3,5-thiadiazines (198) with aliphatic amines at room temperature gives 2,4,5-triarylimidazoles. These may be formed through the Stt 1,3,5-thiadiazine anion (199), which could lose sulfur via a thia-a-homoimidazole (200 Scheme 114). 

There have been reports of a novel synthesis of 2,4,5-trialkyl-imidazoles by the rhodium-catalyzed reactions of alkenes with carbon monoxide and ammonia. Yields are 50-60%. Benzylamine and derivatives react with carbon tetrachloride in the presence of a catalytic amount of metal carbonyls to yield 2,4,5-triarylimidazoles and -imidazolines. The suggested reaction mechanism implicates an initially formed radical species which coordinates with the metal carbonyl. 

Combs et al. have described an unprecedented in situ thermal reduction of the N-0 bond on microwave irradiation at 200 °C for 20 min in the synthesis of 2,4,5-triarylimidazoles from the parent keto-oximes and aldehydes [41]. A similar method has been extended to a short synthesis of lepidiline B (Scheme 10.18) and trifenagrel illustrating the utility of microwave technology [42]. 

Triarylimidazoles This pattern of substitution is the most deeply investigated and the most successfully developed. There are numerous examples in the literature where the target products are achieved efficiently by means of suitable catalyst [22] or MW irradiation [23]. Herein, only some representative examples will be mentioned. 

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