Imidazoles 4-nitro-, tautomerism

This special case of prototropy is known as annular tautomerism (see p 111). In solution, equilibria are established so rapidly that the separate tautomers cannot be isolated. However, their presence can be demonstrated by spectroscopic methods. In this case, e.g. R = CH3, the compound is known as 4(5)-methylimidazole. With certain substituents R, the equilibrium lies predominantly to one side, for instance, in the case of the nitro compound (4-nitroimidazole) or with the methoxy compound (5-methoxy-imidazole). Annular tautomerism has also been demonstrated for 4,5-disubstituted imidazoles ... 

While dealing with imidazoles, an important characteristic is their annular tautomerism. A tautomeric equilibrium for many imidazoles is rapidly achieved at room temperature. In some tautomeric pairs, though, one tautomer often predominates over the other. For instance, 4(5)-bromoimidazole favors the 4-bromo-tautomer in a 30 1 ratio, whereas 4(5)-nitroimidazole exists predominantly as the 4-nitro tautomer (700 1) [11]. 4(5)-Methoxyimidazole has a ratio of 2.5 1 for the 4- and 5-methoxy tautomers. 

In general, IR spectroscopy has neither been a particularly valuable structural tool in imidazole chemistry, nor has it found particular application in tautomerism studies. The IR spectra of nitroimidazoles and their salts have been claimed to indicate that the salt formation involves only the nitro function, with the formation of an isoimidazole ring (17). In polynitroimidazoles only one of the nitro functions appears to be involved in such salt formation <70AHC(12)103, 74CRV279, 80AHC(27)24l). 

Another way to study tautomerism is through p/iTa measurements. A comparison of the basic pATa values for 4(5)-nitroimidazole with those of l-methyI-4- (29) and l-methyl-5-nitroimidazole (30) leads one to the conclusion that the 4-nitro tautomer (28) predominates (Scheme 13) in fact the 4-nitro 5-nitro ratio has been computed as about 400 1. In this experiment the methylated compounds serve as fixed models in which the nitro substituent is fixed in each of the two possible orientations. The influence of the methyl group can be shown to be small by comparison of the pATa values for imidazole ( 7.0) and 1-methyl-imidazole ( 7.1), and hence l-methyl-4-nitroimidazoIe resembles the major tautomer. 

Disubstituted 1/f-imidazoles are classic examples of prototropic annular tautomerism. Depending on the nature of substituents, one tautomer may predominate over the other, as in the case of trifluoromethyl-substituted imidazole 50, where form 50A is the major component in solution in DMSO or CH3CN. In an unusual case, the two tautomers, 4-nitro-5-methoxyimidazole 136A and 5-nitro-4-methoxyimidazole 136B, were found as a 50 50 mixture in the crystal structure (Scheme 30) <2004AXB191>. 

Imidazoles with a ring iV-hydrogen are subject to tautomerism, which becomes evident in unsymmetri-cally substituted compounds such as the methylimidazole shown. This special feature of imidazole chemistry means that to write simply 4-methylimidazole would be misleading, for this molecule is in rapid tautomeric equilibrium with 5-methylimidazole. All such tautomeric pairs are inseparable and the convention used to cover this phenomenon is to write 4(5)-methylimidazole . In some pairs, one tantomer predominates, for example 4(5)-nitroimidazole favours the 4-nitro-tautomer by 400 1. 

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