H Tautomer

The data obtained from all the various physicochemical methods point to the predominance of the H tautomer 12a in the prototropic equilibrium over its 2H counterpart (Scheme 7). 

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. 

The computational results (93JA2465) are consistent with the experimental findings of NMR spectroscopic studies (82JOC5132 97MRC35), which showed the presence of only the H tautomer of tetrazole in DMSO-dfi e = 49) solution. The content of H tautomer 27a in dioxane e = 22) at 30°C was estimated as 78% (82JST283) and 85% (75BSF1675) from its dipole moment 4.88 D and those of 1,5- and 2,5-dimethyltetrazoles as models for the H and 2H tautomers respectively. 

JCS(P2)57]. It follows, therefore, that the destabilizing lone-pair repulsion effeet appeared in the H tautomer 25a overeomes positive eontribu-tion of its greater aromatie stabilization relative to 25b and serves as a major faetor defining the relative stability of the tautomers. 

H tautomer on the triazole nucleus). Only some of this type of compound exhibited slight antibacterial activity (89FA619, 97MI1). 

Aminopyridothiadiazine 2,2-dioxides 126 (X = CR, r = H) were found to exist in water (from UV spectra) and in DMSO-iie (from NMR spectra) exclusively as N(8)H tautomers 126c [86CS607 88AHC(44)81]. This was explained by the strongly acidifying effect of the SO2 function, which makes the formation of a tautomer with the more distant acidic proton energetically more favorable. 

Independently of the substitution, in the solid state compounds 126 (X = N) were found to exist exclusively as N(1)H tautomers 126a [88H(27)2201]. 

When the amino group is substituted by a keto group, the shift of the equlibrium toward the N(8)H tautomer is observed. Thus, in contrast to 126 (X = N), for which N(1)H tautomer 126a predominates in MeOH solution [88H(27)2201], 4-0X0 derivatives 127 exist in MeOH as N(8)H tautomers shown (84JHC861). 

Benzotriazole can exist in two tautomeric forms, l-//-benzotriazole (6.46, R = H) and 2-/f-benzotriazole. If the aromatic ring contains a substituent, the 1- and 3-nitrogen atoms of the triazole are not equivalent, and therefore a 3-//-benzotri-azole derivative can also exist. The equilibrium between the 1 -H and 2-H tautomers of benzotriazoles is strongly on the side of the 1 -H tautomer, in contrast to triazole where the 2-H tautomer is dominant. Tomas et al. (1989) compared experimental data (enthalpies of solution, vaporization, sublimation, and solvation in water, methanol, and dimethylsulfoxide) with the results of ab initio theoretical calculations at the 6-31G level. 

H tautomer. This remarkable difference in reactivity originates from a greater differentiation in bond lengths in the benzenoid ring of 2-substituted benzotriazoles in comparison with their benzotriazol-l-yl analogs. Bonds C(4)-C(5) in derivatives 300 are relatively short (1.377 A) this renders them more double bond character and makes more susceptible to [2+2] cycloadditions <20020L1487>. 

Imino-fe(phosphine chalcogenide)s can in theory exist in two different tautomeric states an N-H tautomer 41a and a E-H tautomer 41b. However, extensive studies in both solution and the solid state have shown that in all cases (with the exception of some dioxo E = O species) the N-H tautomer predominates.75 Structural studies have revealed the N(PE)2 group in 41a to be planar or close to planar, with P-N-P bond angles in the range 122-133°, indicative of substantial sp2 character at the nitrogen centre. Planarity of the nitrogen is also observed in the anionic dichalcogenoimidodiphosph(in)ates 42. 

The monochalcogenides 43 can also theoretically exist in more than one tautomeric form an N-H tautomer 43a, a P-H tautomer 43b or an E-H tautomer 43c. Solution and solid-state studies on these compounds show that, depending upon the nature of the R substituents, either the N-H or the P-H tautomer predominates. Substituents which lead to increased basicity of the phosphorus lone-pair (e.g., R = NMe279, Pr80) have been shown to favour the formation of the P H tautomer, whereas in systems where the phosphorus lone pair is less basic (e.g., R = Ph81) the N-H tautomers are favoured. 

The presence of the cation protonated on N-1 cannot account for the fluorescence of aqueous acidic adenine solutions (pH = 2), since the 1-methyl derivative does not fluoresce under the same conditions (Borresen, 1967). It has therefore been suggested that other tautomeric forms of the cation are also present, the fluorescent tautomer probably being protonated on the amino-group with another proton on N-7. Quantum mechanical calculations (Veillard and Pullman, 1963) indicate similar proton affinity for N-1 and N-3, and a lesser one for N-7. There are numerous calculations in the literature on the electronic structure of adenine (see Boyd, 1972, and references quoted therein) and a recent one on N-7-H and N-9-H tautomers protonated on N-1 (Jordan and Sostman, 1972). The N-9-H form is preferred according to hoth MINDO and CNDO/2 calculations. 

There is also a conformational ambiguity characteristic of the histidine side chain as it is built into electron density maps The two possible orientations about the Cfi-Cy bond are indistinguishable, so the crystal-lographer must select one of these orientations based on chemical intuition [e.g., the availability of hydrogen bond interaction(s) in one particular orientation and not the other]. Additionally, the proper histidine tautomer is likewise selected by chemical intuition. Reynolds et al. (1973) demonstrated that the Ne-H tautomer is the predominant form of free histidine in solution, and these investigators showed that the ratio Ne-H tautomer/N8-H tautomer is approximately 80% 20% (Fig. 13). 

Fig. 13. The Ne-H tautomer of histidine is favored for the free amino acid, but within a protein structure either tautomer may be preferentially stabilized due to hydrogen bond arrangements and other environmental factors. For example, the NS-H tautomer is a frequently observed zinc ligand (Chakrabarti, 1990c).

The vibration spectrum of the first excited state of guanine was measured using laser desorption jet-cooled resonance-enhanced multiphoton ionization (REMPI) spectrometry <1999JA4896>. The millimeter wave spectrum of purine was collected using a free jet spectrometer, and the observed rotational spectrum was assigned to the N(9)-H tautomer <1996CPL189>. 

Pyrolysis of pyrazolo[3,4-b]pyridine247 and the 1-phenyl derivative248 proceed by loss of nitrogen gas. The 1-phenyl derivative, at 770°C, underwent 49% conversion to 4-azafluorene. The formation of a carbene (272) from the 3-H tautomer was proposed because the alternative carbene (273) is known to lead to mixtures of 1- and 3-azafluorenes. 

To explore the importance of the intermolecular interactions model systems were constructed for both the N7-H and the N9-H tautomeric forms. These models, labeled HB N9-H (1) and HB.N7-H (2) in the tables, are based on the X-ray structure of the N7-H tautomer partially surrounded by the nearest neighbor molecules. In the models the position of the nearest neighbor fragments was determined using the x-ray structure and the optimized X-H distances. The models and the numbering of the atoms in purine are shown in Figure 1. 

The NMR results confirm the X-ray determinations that the N7-H tautomer is the most stable in the solid and the DFT calculations agree with all previous evidence that the N9-H tautomer is the most stable in the gas phase. The calculations show good agreement with the experimental values. When intermolecular effects are included in the calculations, they produce significant improvements in the calculated, 5N chemical... 

Theoretical calculations on the 3-H tautomer of l-hydroxy-4-phenyl-5-carboxylic acid 443 (R4 = Ph, R5 = COOH) have been performed using the B3LYP/6-31G(d) (2005RJOC591) method. 

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