A new model for the theoretical tautomeric constant ( K T) calculation of 2-, 3- and 4-substituted pyridines (original) (raw)
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ChemInform, 2011
We have determined the experimental pK a s for the pyridine protonation and pyrrole deprotonation equilibria of the four isomeric (R-, -, γ-, and δ-) carbolines (pyridoindoles) and for the deprotonation of their N-pyrido methylated derivatives. HF 6-31+G* ab initio calculations have been carried out to obtain theoretically the magnitudes of the prototropic equilibria in gas phase and in solution. A cavity model of solvation has been employed. To analyze the influence of annelation and tautomerism, prototropic equilibria of azaindole isomers and H-pyrido tautomers of carbolines, respectively, have also been theoretically studied. Equilibria involving tautomeric species are always energetically unfavored against those of the normal forms. Solvation differently affects the relative gas phase values among isomers within the series and between the same isomers of related series. Solvent damps the magnitude of the gap among azaindole or carboline isomers and can even reverse the acidity sequence. The acidity sequence of theoretical free energies for the pyridine nitrogen deprotonation (γ< <δ<R) and pyrrole nitrogen deprotonation (δ< <R<γ) processes of the carboline normal forms in solution at 298 K are in quite reasonable agreement with those observed experimentally. (6) Balón, M.; Hidalgo, J.; Guardado, P.; Muñ oz, M. A.; Carmona, C.
Bulletin of The Korean Chemical Society, 2011
Under solvent-free conditions and in one-pot, a series of 2-amino-4-aryl-3-cyano-6-(3,4-dimethoxyphenyl)pyridines and 4-aryl-3-cyano-6-(3,4-dimethoxyphenyl)-2(1H)-pyridinones were prepared using 3,4dimethoxyacetophenone, an aldehyde, malononitrile (or ethyl cyanoacetate), and ammonium acetate in the presence of 3-methyl-1-(4-sulfonylbutyl)imidazolium hydrogen sulfate [HO 3 S(CH 2) 4 MIM][HSO 4 ] (a Brønsted acidic ionic liquid) as the catalyst in very short reaction time. The preference for the formation of more stable tautomers was consistence with the theoretical calculation using the Gaussian 03 program at the B3LYP hybrid density functional level.
Absolute and relative pKa calculations of mono and diprotic pyridines by quantum methods
Journal of Molecular Structure: THEOCHEM, 2009
Gas-phase deprotonation free energies and aqueous solvation free energies of 10 monoprotic and 6 diprotic pyridines were calculated using CBS-QB3 and HF/CPCM or B3LYP/CPCM methods. The results have been processed considering three thermodynamic cycles for absolute and relative pK a calculations. In these cycles, different experimental values of solvation free energies for proton, water and hydronium were considered. Moreover, calculated ab initio and DFT values were used when possible. Results show that the inclusion of explicit single water molecule interacting with pyridine nitrogen improves predictions in 1.5 pK a units. Water molecule causes an increase in the solute-solvent surface interaction and allows the continuum method to reproduce correct solvation free energy differences between acids and bases. The correct combination of computational methodology and thermodynamic cycle leads to very accurate results, with mean absolute errors of 0.3-0.5 pK a units for monoprotic and 0.7-0.9 pK a units for diprotic pyridines.
Theoretical Study of the Tautomeric Preference and Self Association Processes of 2-Pyrrolidinone
2011
Relative tautomerization energies, dipole moments for the tautomers of 2-pyrrolidinone was studied by quantum-chemical calculations, using the B3LYP level of calculation with the 6-311G(d,p) basis set in the gas phase with full geometry optimization. Entropies, enthalpies and Gibbs free energies for the tautomerization process of 2-pyrrolidinone was obtained using the RHF/6-31G(d) level of computation. The calculations showed that, the Keto form is the most stable form in the gas phase. The entropy effect on the Gibbs free energy change of the tautomerization process 2-pyrrolidinone is found to be very small, and has practically no significance for the tautomeric equilibria of the 2-pyrrolidinone. The enthalpic term is dominant in the determination of the equilibrium constant. The ability to form dimer, trimer and tetramer was investigated concerning the energetical changes; dipole moments using the RHF/6-31Gd level of computation. The thermodynamic parameters at different temperatu...
2-Phenacylpyridines substituted in the benzene ring are in equilibrium with (Z)-2-(2-hydroxy-2-phenylvinyl)pyridines when dissolved in chloroform. The substituent affects significantly the tautomeric equilibrium [the amount of the enolimine form stabilized by the intramolecular hydrogen bond is 1 and 92% for R = p-N(CH 2) 4 and p-NO 2 , respec-tively]. The negative logarithm of the tautomeric equilibrium constant, K T , is linearly dependent on the Hammett σ substituent constants. The dependence of K T vs. temperature is exponential in character: the more electron-withdrawing is the substituent, the more distinct is the influence of temperature. Unexpectedly, the tautomer present in the crystalline state is not the same for all compounds studied (it is the ketimine one for those carrying strong electron-donor groups). Among the different ab initio methods used to calculate the enthalpy of the proton transfer in chloroform solution, MP2/6-31G** gives the best results.
International journal of molecular sciences, 2016
The gas-phase thermal tautomerization reaction between 2-hydroxypyridine (2-HPY) and 2-pyridone (2-PY) was investigated by applying 6-311++G** and aug-cc-pvdz basis sets incorporated into some density functional theory (DFT) and coupled cluster with singles and doubles (CCSD) methods. The geometrical structures, dipole moments, HOMO-LUMO energy gaps, total hyperpolarizability, kinetics and thermodynamics functions were monitored against the effects of the corrections imposed on these functionals. The small experimental energy difference between the two tautomers of 3.23 kJ/mol; was a real test of the accuracy of the applied levels of theory. M062X and CCSD methods predicted the preference of 2-HPY over 2-PY by 5-9 kJ/mol; while B3LYP functional favoured 2-PY by 1-3 kJ/mol. The CAM-B3LYP and ωB97XD functionals yielded mixed results depending on the basis set used. The source of preference of 2-HPY is the minimal steric hindrance and electrostatic repulsion that subdued the huge hyper...
Prediction of the Basicities of Pyridines in the Gas Phase and in Aqueous Solution
Journal of Chemical Information and Modeling, 2010
The basicities of 125 pyridine derivatives in the gas phase and in water have been correlated with the electron density properties within the framework of quantum topological molecular similarity (QTMS). We used the theory of quantum chemical topology (QCT) to provide ab initio descriptors that are able to predict pK b values. Partial least squares (PLS) and the machine-learning technique Kriging generated validated models. Properties were considered for systems in their neutral and protonated forms. The compounds were divided into a training set, used to develop the models, and a test set, for which the predicted values of the different models were compared with the experimental ones. The results were found to be good for those compounds with substituents in the meta and para positions, whereas the use of Kriging was required to obtain reasonable results when ortho derivatives were included. The basicity was found to be better described in the gas phase than in water. Special attention was paid to external validation.
Journal of Molecular Structure-theochem, 1999
The geometries, relative stabilities, proton affinities for the different tautomers of 2-, 4-and 5-pyrimidones and their thio-and azo analogs along with their fixed forms (i.e. model compounds in which proton migration is eliminated) were calculated with full geometry optimization using AM1, PM3 and MNDO methods. The predominance of oxo forms over hydroxy forms were confirmed with all three methods, as cited in the literature, with the exception of AM1 and MNDO methods which both indicate the predominance of 2-and 4-hydroxypyrimidines over oxo forms with a stability energy value of Ϸ 2 and 8 kcal mol −1 for the main tautomers. For azo analogs the predominance of amino forms over imino forms were confirmed with the exception of the AM1 method which indicates the predominance of 5-iminopyrimidine over amino forms with stability energy values of Ϸ 28 kcal mol −1 for the main tautomers. For the thio analogs the predominance of thiol forms over thione forms were confirmed with the PM3 and MNDO methods; the AM1 method however, indicates the predominance of the 2-thione form over the thiol form with a stability energy value of Ϸ 1 kcal mol −1 . ᭧
Journal of the American Chemical Society, 1991
The gas-and aqueous-phase basicities have been determined for an extensive series of 2-, 3-, and 4-substituted pyridines, quinoline, and isoquinoline. Gibbs free energies and enthalpies of aqueous protonation, heats of vaporization, and heats of solution have been measured for many of the substituted pyridines, where reliable data were not available from the literature. This combination of gas-and solution-phase data makes possible a complete thermodynamic analysis of basicities and solvation energies for a large number of pyridines via the thermodynamic cycle in Scheme I. The gas-and aqueous-phase free energies of protonation correlate roughly with one another, but with an approximate 2-fold attenuation of the gas-phase substituent effects in the aqueous basicities. The correlations for the free energies and enthalpies of protonation show a 2.4-2.5-fold attenuation factor for the 3-and 4-substituted pyridines. The 2-substituted pyridines give correlations for the free energies and enthalpies with attenuation factors of 1.4 and 1.7, respectively. Only the 2-and 4-aminopyridines, 2,6-di-tert-butylpyridine, 2-phenylpyridine, methylnicotinate, and methylisonicotinate deviate substantially from the correlations. The aminopyridines exhibit anomalously high aqueous basicities as a result of increased solvation at the high charge densities on the resonance-stabilizing 2-and 4-amino groups of the pyridinium ions, an effect not observed for the 3-amino group or dimethylamino groups. Analysis of the data here permits a separation of Hepler's intrinsic and extrinsic (solvation) effects in the aqueous equilibria for proton transfer. The solvation effects for the pyridines and pyridinium ions have been separated into terms for cavity formation, van der Waals interactions and solvent structure-making by alkyl groups, dipole-solvent interactions, and charge-solvent interactions. The changes in solvation of substituted neutral pyridines are mainly due to changes in the dipolar solvation term, which correlates with the dipole moment. The primary solvation term responsible for the attenuation of the gas-phase basicity differences on passing into aqueous solution is the chargesolvent interaction term. This term decreases with increasing charge delocalization for charge-stabilizing substituents and increases with increasing charge density at the ring NH for inductively destabilizing substituents. These electrostatic charge solvation terms correlate closely with stabilization energies and semiempirical and ab initio calculated charge densities at the ring NH.