Quantum chemical calculation of tautomeric

Quantum-chemical calculation of the relative stabilities <1989JST(184)179> of tautomeric forms B and C of substituted 2-hydroxy- and 2-mercaptothiophenes have been carried out by the AMI and PM3 methods. The calculation results shown in Table 78 indicate a definite preference for the thiol form in the case of 2-thiophenethiols 248 and similar A77 values for the formation of all three tautomeric forms in the case of 2-hydroxythiophenes, which corresponded to the experimental data . The effect of substituents on the relative stabilities for hydroxy- and mercaptothiophenes is identical and in complete qualitative accord with the empirical data obtained for hydroxythiophenes substituents at C-3 and C-4 stabilize to form 249, while substituents at C-5 stabilize to form 250 (Scheme 20) <1997CHE1047>. 

Table 78 Quantum-chemical calculation of the relative stabilities of tautomeric forms 248-250 of R-substituted 2-thiophe-nethiols and analogously substituted potential 2-hydroxythiophenes 186 ...

N NMR spectroscopy was used to study the tautomerism of adenine derivatives enriched by the N-15 isotope." These enriched samples were prepared as probes for further biochemical studies. While tautomeric mixtures of N -H and N -H were reported for adenine and 2-MeS-adenine based on the " N NMR spectra, an N -H species was suggested for the solution of S-Br-adenine. These observations were supported by quantum chemical calculation of the individual tautomeric forms for isolated molecules and for the inclusion of solvent effects (both continuum and discrete models). 

Many computational studies in heterocyclic chemistry deal with proton transfer reactions between different tautomeric structures. Activation energies of these reactions obtained from quantum chemical calculations need further corrections, since tunneling effects may lower the effective barriers considerably. These effects can either be estimated by simple models or computed more precisely via the determination of the transmission coefficients within the framework of variational transition state calculations [92CPC235, 93JA2408]. 

As is common in heterocyclic chemistry, many studies concern tautomeric equilibria. While quantum chemical calculations are straightforward for the question of the most stable isomer, experiments are sometimes very demanding. Therefore, quantum chemistry can easily provide answers that may require substantial experimental effort. Comparatively few studies concern the investigation of entire reaction paths. This is much more demanding than computing a limited number of tautomers, of course, but usually provides a very detailed picture of the reaction mechanism. In certain cases, it was only possible to judge the nature of a chemical reaction on the basis of quantum chemical calculations. 

The solvent effect on the azo-hydrazone equilibrium of 4-phenylazo-l-naphthol has been modelled using ab initio quantum-chemical calculations. The hydrazone form is more stable in water and in methylene chloride, whereas methanol and iso-octane stabilise the azo form, The calculated results were in good agreement with the experimental data in these solvents. Similar studies of l-phenylazo-2-naphthol and 2-phenylazo-l-naphthol provided confirmation. Substituent effects in the phenyl ring were rationalised in terms of the HOMO-LUMO orbital diagrams of both tautomeric forms [53]. 

The keto radical is reduced and further protonated. The function of yohimbine-H+ is to catalyze the tautomerization and to enantioselectively protonate the final carbanion. It is also concluded that the hydrophobic yohimbine is enriched near the hydrophobic cathode surface. Quantum chemical calculations demonstrate that si protonation of the intermediate anion by yohimbine-H+ to give the (i )-dihydroproduct is energetically favored [389, 390]. Similarly, 3-methylinden-l-one in the presence of strychnine yields 71% 3-methylindan-1-one with 35% ee (S -enantiomer). 

The kinetics and mechanism of pyrrole pyrolysis were investigated by ab initio quantum-chemical calculations. It was revealed that pyrrole undergoes tautomerization to form 2H- and 37/-pyrroles prior to any thermal decomposition. It has been shown that the major product, HCN, arises from a hydrogen migration in pyrrole to form a cyclic carbene with the NH bond intact. Ring scission of the carbene leads to an allenic imine of HCN and propyne which is the lowest energy pathway. The 277-pyrrole... 

There is an excellent correlation between the experimental microwave dipole moments of a variety of azoles and those calculated by the ab initio method at the 6-31G //6-31G level p,exp = 0.942p,ca, + 0.008 (86JPC5597). With this equation, the experimental values for 1H- and 2H-1,2,3-triazole are predicted as 4.35 D and 0.32 D, respectively (89JCO(10)426). Thus, quantum chemical calculations are a valuable aid in estimating tautomeric equilibria by dipole moment studies (90ZN(A)1328). 

The structure of the reaction product of 2-aminopyridine and diethyl malonate, described by Chichibabin as 2,4-dioxo-3,4-dihydro-2//-pyrido-[l,2-<7]pyrimidine,96 was first questioned by Snyder and Robison253 on the basis of the high melting point and poor solubility of the compound. They suggested the tautomeric 2-hydroxy-4-oxo-4H-pyrido[l,2-a]pyrimidine structure. The problem was solved by Katritzky and Waring273 who compared the UV spectrum of the product with that of fixed tautomers and found that the product may best be described as anhydro- 2-hydroxy-4-oxo-4/f-pyrido[l,2- ]pyrimidinium)hydroxide (63). Because of the chemical behavior of these compounds, however, the contribution of other mesomeric forms to the structure has also been considered.122 Thus, PPP-SCF quantum chemical calculations suggest that 1,4-dipolar cycloadditions to the C-3 and C-9a atoms are to be expected.352 This type of reaction does in fact occur (see Section III,C,10). Katritzky and Waring273 estimated the ratio of the mesomeric betaine (63 R = H) and the 2-hydroxy-4-oxo tautomers to be about 20 1. 

This paper presents quantum mechanical studies of the, 5N and, 3C chemical shifts in both the N7-H and N9-H tautomeric forms of purine. Quantum mechanical calculations of the chemical shifts were used to assign the NMR resonances and the spatial orientation of the principal axes of the chemical shift tensors. Calculations in purine and in a pyridine-methanol complex model provide insights on the importance of the intermolecular interactions on the chemical shifts of the nucleic acid bases. 

A strained azo-bridged tricyclic system (1) undergoes a selective retro inverse electron-demand Diels-Alder reaction on heating, leading through a cascade of tautomeric and sigmatropic shifts to the pyridazine derivative (2) (Scheme 2).16 The proposed mechanism was supported by quantum chemical calculations and experimental evidence. 

The problem of tautomeric equilibriums in annelated 1,5-diazepines was studied in [68] by means of NMR spectroscopy, X-ray analysis and quantum-chemical calculations. It was shown that the electron-withdrawing rings (e.g., pyrimidine moiety) fused with the diazepine cycle increase the stability of the antiaromatic enamine tautomeric forms A and C, while in the case of benzodiazepine, a diimine tautomer B was found to be the most stable. Ab initio quantum-chemical calculations and NMR spectroscopic data showed that solvation of seven-membered heterocycles with polar solvents contributes considerably to the stabilization of the enamine forms A and C. This assumption was also proven by X-ray analysis, which showed that in the solid state these diazepines exist in the diimine form B. 

Investigations on tautomerism in most cases proved the predominant or exclusive existence of imino rather than amino forms. These conclusions were derived from electronic and other spectra, quantum chemical calculations (MNDO 92JHC1219), and reactivities. Thus, imidazotroponeimine 575a lacks amine reactions (53MI1) its 2-amino derivative 14c is diazotized at the 2-position (62BCJ1188). 

Tautomeric equilibrium in aqueous cw-malonaldehyde, see reaction 1 in Figure 8-4, is a prototypical reaction extensively studied in the gas phase but still relatively unknown in solution. In fact, despite the large number of NMR experiments [52,53,54] and quantum chemical calculations [55] with the polarized continuum model (PCM), [1] the actual stability of czT-malonaldehyde is not well clarified, although the trans isomer should be the predominant form in water. Secondly, the involvement of the light proton in the reaction may in principle provide relevant quantum effects even in condensed phase. All these complications did not prevent this reaction to be used as a prototypical system for theoretical studies of intramolecular proton transfer in condensed phase by several investigators [56,57,58,59,60] including ourselves. 

Firstly, the nondegenerated tautomers of 3-nitro-l,2,4-triazole-5-one (NTO) radical anions were investigated by ESR method during electrochemical reduction of NTO in aprotic medium at different temperatures. It was shown that observed reversible temperature variations in the ESR spectra of radical anions were caused by tautomerism. Quantum chemical calculations evidence that l,4-/f-tautomer of radical anion is most preferable [881],... 

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