Imidazole tautomers

Compared to burimamide, the percentage of ionized imidazole ring has been lowered in metiamide and the ratio of the two possible un-ionized imidazole tautomers reversed. The fact that activity is increased with respect to thiaburimamide suggests that the increase in the population of tautomer (I) outweighs the increase in population of the ionized tautomer (III). 

CP-MAS NMR spectra were employed as well to assign aimular tautomerism in the solid state, for example, to identify one or the mixture of two imidazole tautomers [94], but 5( C) differences are much smaller. 

Annular tautomerism (e.g. 133 134) involves the movement of a proton between two annular nitrogen atoms. For unsubstituted imidazole (133 R = H) and pyrazole (135 R = H) the two tautomers are identical, but this does not apply to substituted derivatives. For triazoles and tetrazoles, even the unsubstituted parent compounds show two distinct tautomers. Flowever, interconversion occurs readily and such tautomers cannot be separated. Sometimes one tautomeric form predominates. Thus the mesomerism of the benzene ring is greater in (136) than in (137), and UV spectral comparisons show that benzotriazole exists predominantly as (136). 

The same system of nomenclature can be used to differentiate tautomers of types 22 and 23, which would be named 4-methyl-IH-imid-azole and 4-methyl-3//-imidazole, respectively. 

It is well accepted that tautomerism relates to the equilibrium between two or more different tautomers e.g., it corresponds to determining if the structure of a compound is, for instance, a pyridone or an hydroxypyridine. The kinetic aspects are often neglected and when the tautomeric equilibrium constant, Kt, is equal to 1 (e.g., for imidazole), the problem may seem... 

Aminoacids and other molecules of biological interest. Histamine 14, like guanine, has nonstandard numbering tautomers 14a and 14b are called N(3)H and N(1)H instead of 4- and 5-aminoethyl, like other imidazoles. In... 

Annular tautomerism of azoles and benzazoles [the nonaromatic tautomers of imidazole 17, 2H and 4(5)H have been calculated at the MP2/6-31G level to be about 15 kcal mol less stable than the IH tautomer (95JOC2865)]. We present here the case of 4(5)-substituted imidazoles, different from the histamine, histidine, and derivatives already discussed. By analogy with these histamines, 4-methylimidazole 17a is often named distal [N(t)H] and 5-methylimidazole 17b, proximal [N(7t)H] (Scheme 9). 

The main conclusion on the influence of substituents in the imidazole ring on the state of the tautomeric equilibria 14a 14b is that electron-withdrawing groups favor the 4-position, i.e., the tautomers 14a with = Hal, NO2, and so on, are the energetically preferable species. Application of Charton s equation, Kt = [4-R Im]/[5-R Im] = 3.2 was discussed in detail [76AHC(S1) 96CHEC-II(3)77]. The equation was found to be in a qualitative agreement with the experimental data presented in Table III. 

Theoretical studies of the relative stabilities of tautomers 14a and 14b were carried out mostly at the semiempirical level. AMI and PM3 calculations [98JST(T)249] of the relative stabilities carried out for a series of 4(5)-substituted imidazoles 14 (R = H, R = H, CH3, OH, F, NO2, Ph) are mostly in accord with the conclusion based on the Charton s equation. From the comparison of the electronic spectra of 4(5)-phenylimidazole 14 (R2 = Ph, R = R3 = H) and 2,4(5)-diphenylimidazole 14 (R = R = Ph, R = H) in ethanol with those calculated by using ir-electron PPP method for each of the tautomeric forms, it follows that calculations for type 14a tautomers match the experimentally observed spectra better (86ZC378). The AMI calculations [92JCS(P1)2779] of enthalpies of formation of 4(5)-aminoimidazole 14 (R = NH2, R = R = H) and 4(5)-nitroimidazole 14 (R = NO2, R = R = H) point to tautomers 14a and 14b respectively as being energetically preferred in the gas phase. Both predictions are in disagreement with expectations based on Charton s equation and the data related to basicity measurements (Table III). These inconsistencies may be... 

The conclusions about the influence of azole ring substituents on the tautomeric equilibria are summarized in Table VIII. Although sufficient data are available for pyrazoles and imidazoles, it is difficult to correlate them within any well-defined scheme. The energy differences between pairs of tautomers are generally quite small and attempts to analyze these using, for example, the Taft-Topson model failed [95JCR(S)172]. In the case of mono-substituted compounds, Hammet-type equations... 

Imidazole solution, and solid state Equivalent the IH tautomer Electron-withdrawing group prefers 4-... 

Even in tricyclic bis-imidazole 57, for which the potential imino-tautomer 57b would be stabilized by the intramolecular N-H -N bond, the only observable form is the amino tautomer 57a (Scheme 30) [73KGS807 76AHC(S1), p. 431]. 

The thione tautomer 177b is the predominant form of 2-mercaptobenz-imidazoles 177 both in solution [76AHC(S1), p. 401] and in the solid state (Scheme 64) [76AX(B)345]. 

MO studies (AMI and AMI-SMI) on the tautomerism and protonation of 2-thiopurine have been reported [95THE(334)223]. Heats of formation and relative energies have been calculated for the nine tautomeric forms in the gas phase. Tire proton affinities were determined for the most stable tautomers 8a-8d. Tire pyrimidine ring in the thiones 8a and 8b has shown a greater proton affinity in comparison with the imidazole ring, or with the other tautomers. In solution, the thione tautomers are claimed to be more stabilized by solvent effects than the thiol forms, and the 3H,1H tautomer 8b is the most stable. So far, no additional experimental data or ab initio calculations have been reported to confirm these conclusions. 

Tile data on H- and C-cliemical shifts, H-relaxation rates, and protonation for 2-arylimidazo[l,2- ]imidazoles (107) and their methyl derivatives 108 and 109 indicate that 107 exists predominantly as the 1/7 tautomer 107a in CDCI3 and as the IH tautomer 107b in DMSO-dg or CD3OD-D2O (91MRC1147). An X-ray crystallographic study has demonstrated the IH tautomer 107a in the lattice. 

All triazoles, tetrazoles, and unsymmetrically substituted imidazoles and pyrazoles can exist in two tautomeric forms, e.g., 1 2 and 3 4. However, attempts to isolate the individual tautomers have been unsuccessful, always leading to one isomer (for summaries of this aspect of the tautomerism of imidazoles, see references 1 and 2). Although the isolation of both tautomers of a number of com-... 

Tanokura M (1983) 1 II-NMstudy R on the tautomerism of the imidazole ring of histidine residues I. Microscopic pK values and molar ratios of tautomers in histidine-containing peptides. Biochim Biophys Acta 742 576-585. 

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