Benzimidazoles methyl-, tautomerism

Benzimidazole, 2-amino-5-bromo-l-methyl-diazo coupling, 5, 429 Benzimidazole, 2-amino-6-bromo-1 -methyl-diazo coupling, 5, 429 Benzimidazole, 2-amino-1-ethyl-alkylation, 5, 438 Benzimidazole, 2-amino-1-methyl-acylation, 5, 438 bromination, 5, 429 tautomerism, 5, 368 Benzimidazole, 4-amino-2-methyl-diazo coupling, 5, 429 Benzimidazole, 2-aroyl-mass spectra, 5, 360 Benzimidazole, 1-aryl-metallation, 5, 448 reactions... 

Not much information has been added in recent years to the earlier studies of tautomeric equilibria of benzimidazoles based on basicity measurements [76AHC(S1), p. 292]. For 5(6)- and 4(7)-substituted benzimidazoles and 2-methyl-5(6)-substituted benzimidazoles values are very close to 1, which indicates near equivalence in the stability of N1(H) and N3(H) tautomers. The tautomeric equilibria of 2-substituted (H, NH2, OMe, CN) 5-nitrobenzimidazoles and 4-nitrobenzimidazoles were analyzed with the use of semiempirical MINDO/3 and INDO methods. It was predicted that electron-releasing groups in position 2 shifted the equilibria to the 6-NO2 and 4-NO2 tautomers, respectively. 

By using basicity data, Ridd and Smith- showed that 5-nitro- and 5-chloro-benzimidazole and their 2-methyl analogs exist essentially as mixtures of equivalent amounts of 29 and 30, and, in agreement with this ratio, 5-substituted benzimidazoles form comparable amounts of 1- and 3-derivatives on alkylation,- showing earlier alkylation ratios- to be erroneous. There are, however, other factors which can lead to the predominance of one tautomeric form. Basicity measurements indicate that 31 is preferred to the alternative non-hydro-... 

The SCF calculations (Section 4.06.2) predict the sequence of electrophilic attack in benzimidazole as 7 > 6 > 5 > 4, although positions 4 and 7, and 5 and 6 are tautomerically equivalent in iV-unsubstituted benzimidazoles. Substitution appears to occur with greatest facility in the 5- (or 6-) positions. Bromination in acetic acid of 2-amino-l-methylben-zimidazole occurs at C-6. It can be seen from Table 5 (Section 4.07.1.4.5) that aqueous bromination of benzimidazole itself occurs most readily at C-5, followed by C-7, as it does in the 1- and 2-methyl analogues (78JCS(P2)865). Some of the experimental results are summarized in Scheme 93. Chlorination of both benzimidazole and 2-methylbenzimidazole give the 4,5,6-trichloro product. Nitration and sulfonation, too, occur most readily at position 5 with either sulfuric or chlorsulfonic acids being effective in the latter reaction. 

Examples of ring-chain tautomerism in this ring system have been observed by spectral methods. Thus, 3-hydroxy-2,3-dihydrothiazolo-[3,2-a]benzimidazole and its 3-trifluoromethyl analogue exist exclusively as the cyclic carbinolamines (283a R = H or CFj) in both the solid and dissolved states. The 3-methyl homologue (283 R = Me) exists as (283a) in the solid state, but as a 1 2-mixture of (283a) and the open-chain... 

The tautomerism of 3-methyl-s-triazolo[4,3-fl]benzimidazole 106 was established from the C-chemical shifts (in DMSO-de) of the parent compound and its N-methylated derivatives (78BSF273). Tautomers 106a and 106b are both present in DMSO, whereas 106a is predominant in ethanol and 106b in dioxane (UV spectroscopy) (75JHC197). The interpolation of C-chemical shifts was suggested for calculations of tautomeric equilibrium constants. 

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