2- benzimidazole, theoretical studies

The reaction of iV-(2,4-dinitrophenyl)amino acids with base in aqueous dioxane has been shown to give benzimidazole iV-oxides (7). The rate-determining step is likely to be formation of an iV-alkylidene-2-nitrosoaniline intermediate (6), which is followed by rapid cyclization and decarboxylation.19 The loss of carbon dioxide from perbenzoate anions has been investigated by mass spectrometry and electronic structure calculations. The results, including isotopic labelling experiments, support a mechanism involving initial intramolecular nucleophilic attack at either the ortho- or ipso-ring positions. They also indicate that epoxides may be intermediates en route to the phenoxide products.20 There has also been a theoretical study of the formation of trichlorinated dibenzo-/ -dioxins by reaction of 2,4,5-trichlorophenolate ions with 2,4-dichlorophenol.21... 

We have carried out a theoretical study on the related cases of imidazoles (126) and benzimidazoles (127) [128],... 

AMI semiempirical calculations have shown that, as far as tautomerism is concerned, there is a structural relationship between jS-dicarbonyl compounds and NH-pyrazoles, and in a wide variety of NH-pyrazoles studied " the most stable tautomer was found to be that having the largest single-bond character between the C(3)—C(4) bond. The problem of proton transfer in NH-pyrazole crystals has been subjected to a detailed theoretical study, while a study of the tautomerism of 2-aryl and 2-heteroaryl derivatives of benzimidazole has indicated that tautomerism takes place by the intermolecular relay of protons between stacked molecules. The first report of the stable co-existence of two different histidine tautomers in one peptide crystal structure has appeared. Ab initio calculations have been used to study the tautomerism of both histamine and pyrazolo[3,4-i/]pyridazine in the gas phase and in aqueous solution, and a theoretical study of the NH tautomerism in free-base porphyrin has been undertaken. ... 

Imidazoles and benzimidazoles unsubstituted on nitrogen exhibit fast prototropic tautomerism which leads to equilibrium mixtures of unsymmetrically substituted compounds, for example, 4(5)-substituted imidazoles, 4(7)- or 5(6)-substituted benzimidazoles. The proton exchange is an intermolecular process (which may involve a protic solvent), and is so fast on the NMR time scale that only one species is usually apparent in the spectrum. iV-Substituted azoles cannot exhibit such tautomerism, and strongly acidic media also inhibit proton exchange. Much work since the mid-1980s has focussed on determination of the proportions of isomers in tautomeric mixtures, with theoretical studies applied to the gas phase (and solution), and solid state studies are also receiving considerable attention. Extrapolation of the results of gas phase and solid state studies to solution, though, can only be less than perfect. 

Very few theoretical studies concern these systems. An example using TD-DFT and the localized density matrix (LDM) method approaches to calculate the electronic spectra of 2-(2 -pyridyl)benzimidazole (111) and its boron and beryllium derivatives 112-114 has been reported recently (10THE(955)7). 

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