Tautomerism of derivatives of azines. 18. Effect of solvents on intrachelate tautomerism of the [1,5]-sigmatropic type in the acylmethylazine series

The constants of the intrachelate tautomeric equilibria of trifluoro- and trichloroacetonylpyridines in aprotic and hydroxy-containing solvents were determined by ¹H, ¹⁴N, and ¹⁷O NMR spectroscopy and UV spectrophotometry. It is shown that an increase in the polarity of the solvent and transition to hydroxy-containing solvents are accompanied by a shift of the intrachelate equilibrium to favor the ylidene tautomer.See [1] for Communication 17.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 514–520, April, 1988.     

Tautomerism of pyrimidyl-2-methane derivatives: medium effects,thermodynamics, kinetics and mechanism

The Investigation of tautomeric equilibria among pyrimidyl-2-methanes has been undertaken. Pyrimidyl-pyrimidyledene equilibrium has been found in the case of 5-substituted 2-pyrimidyl-cyanoacetic esters. Unsymmetrically substituted pyrimidyl-2-methanes form two types (1-NH and 3-NH) of ylidene tautomers, which differ in ring proton spin coupling constants. The effect of substituents in the pyrimidine ring and of the solvent on tautomeric equilibrium are discussed. A drastic effect is produced by acids (CF₃ COOH) which shift the equilibrium toward the ylidene tautomer of higher basicity. The thermodynamic and kinetic characteristics and the mechanism of the tautomeric equilibrium were examined.     

Tautomerism of derivatives of azines. 16. Tautomerism of acylmethylpyrazines and -quinoxalines

The tautomeric equilibria of acylmethylpyrazines and -quinoxalines in chloroform were studied by ¹H, ¹⁴N, and ¹⁷O NMR spectroscopy. It was shown that keto-enol tautomerism is realized in the acylmethylpyrazine series. Annelation leads to the development of an ylidene tautomer in the acylmethylquinoxaline series. A marked dependence of the position of the intrachelate equilibrium on the character of the solvent was observed.See [1] for Communication 15.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1663–1667, December, 1987.     

Tautomerism of azine derivatives. 6. Tautomerism of 2-pyrimidinylmethane derivatives

The existence of a pyrimidinyl-pyrimidinylidene tautomeric equilibrium in solutions of 2-pyrimidinylcyanoacetic acid esters in CDCl₃ was observed. Unsymmetrically substituted compounds form two types of ylidene tautomers that differ with respect to the position of the NH proton, the ratio between which is controlled by the substituents in the 4 (6) position. The introduction of both donor and acceptor substituents into the 5 position of the pyrimidine ring increases the amount of the pyrimidine form. The same thing occurs when the polarity of the solvent is decreased. The addition of DMSO or DMF to CDCl₃ leads to conversion of the intrachelate ylidene tautomers to unchelated tautomers. Protonation (CF₃COOH) shifts the equilibrium to favor the ylidene tautomer that has higher basicity.See [1] for communication 5.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 827–831, June, 1984.     

Theoretical investigation of solvent effects on tautomeric equilibrium of 2‐diazo‐4,6‐dinitrophenol

The density functional theory has been used to study the tautomeric equilibrium of 2‐diazo‐4,6‐dinitrophenol(DDNP) in the gas phase and in 14 solvents at the B3LYP/6‐31G* level. The solvent effects on the tautomeric equilibria were investigated by the self‐consistent reaction field theory (SCRF) based on conductor polarized continuum model (CPCM) in apolar and polar solvents and by the hybrid continuum‐discrete model in protic solvent, respectively. Solvent effects on the computed molecular properties, such as molecular geometries, dipole moments, E_LUMO, E_HOMO, total energies for DDNP tautomers and transition state, tautomerization energies and solvation energies have been found to be evident. The tautomeric equilibrium of DDNP is solvent‐dependent to a certain extent. The tautomer I (cyclic azoxy form) is preferred in the gas phase, while in nonpolar solvents tautomer I and II (quinold form) exist in comparable amounts, and in highly polar solvents, the tautomeric equilibrium is shifted in favor of the more polar tautomer II . © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Chemistry of naphthazarin derivatives. 9. Direct observation of prototropic tautomerism of (poly)hydroxynaphthazarins by IR spectroscopy

A series of substituted (poly)hydroxylated naphthazarins (5,8-dihydroxy-1,4-naphthoquinones) were synthesized. In general, (poly)hydroxynaphthazarins exist in organic aprotic solvents as mixtures of tautomeric 1,4-naphthoquinonoid forms (IR data). The ratio of tautomers was determined for the first time. The effects of the nature of substituents and the solvent polarity on the tautomeric equilibrium were qualitatively estimated.     

2,6-二巯基吡啶互变异构平衡体系溶剂效应的理论研究

在气相及甲苯、氯仿、乙腈和水等溶剂中对2,6-二巯基吡啶及其硫酮式互变异构体进行了HF/6-31G^**水平上的优化,其中溶液中的计算采用Onsager自洽反应场(SCRF)模型.探讨了溶剂对体系几何结构和能量的影响.结果表明:溶剂的存在与极性的增加有利于平衡体系中硫酮式异构体的存在.     

Tautomerism of derivatives of azines. 19. Effect of solvents on the o,p-quinoid equilibria of the ylidene forms of 4-pyrimidinylcyanoacetic acid esters

The effect of solvents on the tautomeric equilibria of the ylidene forms of 4-pyrimidinylcyanoacetic acid esters with o- and p-quinoid orientations of the double bonds in the heteroring was determined. The relative stability of the p-quinoid tautomer increased markedly on passing to polar solvents due to nonspecific solvation and the formation of hydrogen bonds.See [1] for Communication 18.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 521–524, April, 1988.     

Study of the tautomerism of 2-ethoxycareonyl-3-oxo derivatives of quinuclidine and benzo[b]quinuclidine

The tautomerism of 2-ethoxycarbonyl-3-oxoquinuclidine and 2-ethoxycarbonyl-3-oxobenzo-[b]quinuclidine was investigated by means of IR and UV spectra and potentiometric titration. It was found that tautomeric equilibrium between the ketone, enol, and internally ionized forms is realized for 2-ethoxycarbonyl-3-oxoquinuclidine, and the position of the equilibrium is determined by the aggregate state of the substance and the nature of the solvent. The internally ionized form predominates in the crystals and in polar solvents (alcohol and water), while the ketone and enol forms are the primary ones in solvents of low polarity (chloroform and dioxane), and the percentage of the ketone form is always larger than that of the enol form. In contrast to this, 2-ethoxycarbonyl-3-oxobenzo[b]quinuclidine exists practically completely as the keto form in crystals and solutions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 229–233, February, 1972.     

Synthesis of di- and tetrahydropyrroles.

It was established by means of PMR spectroscopy that the ring-chain tautomeric equilibrium in solutions of 2,3,3-trimethyl-2-hydroxy-5-pyrrolidone and its N-substituted erivatives is shifted exclusively or primarily to favor the cyclic form and that the nature of the solvent has little effect on the position of the equilibrium. An increase in the temperature or the electron-acceptor character of the substituent attached to the nitrogen atom promotes an increase in the percentage of the open forms. The time required to establish the tautomeric equilibrium was determined.See [1] for communication XI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 787–791, June, 1975.     

Chemistry of naphthazarin derivatives. 12. Synthesis and investigation of prototropic tautomerism of 3-(alk-1-enyl)-2-hydroxynaphthazarins

Substituted 3-(alk-1-enyl)-2-hydroxynaphthazarins were synthesized. According to data from IR spectroscopy, these compounds exist in organic aprotic solvents as mixtures of tautomeric 1,4-naphthoquinonoid forms. The compositions of tautomeric mixtures were quantitatively determined. The effects of the structure of the alkenyl substituent and the polarity of the solvent on the tautomeric equilibrium were qualitatively estimated.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2519–2525, November, 2004.     

Synthesis of some new anils: part 1. Reaction of 2-hydroxy-benzaldehyde and 2-hydroxynaphthaldehyde with 2-aminopyridene and 2-aminopyrazine

New Schiff bases derived from 2-aminopyridene and 2-aminopyrazine have been synthesized. The UV-Visible spectra of the compounds have been investigated in acetonitrile and toluene. The compounds were in tautomeric equilibrium (enol-imine O- H...N, keto-amine O...H-N forms) in polar and nonpolar solvents. For some derivatives the keto-amine form was observed in both toluene and acetonitrile. 1H-NMR and IR results showed that all Schiff bases studied favor the enol-imine form over the keto form in a weakly polar solvent such as deuterochloroform.     

Tautomeric equilibria of pyridoxal-5'-phosphate (vitamin B6) and 3-hydroxypyridine derivatives: a theoretical study of solvation effects

The tautomeric equilibria of a series of 3-hydroxypyridine derivatives including pyridoxal-5'-phosphate (PLP), the active form of vitamin B(6), have been studied using density functional calculations (B3LYP/6-311+G//B3LYP/6-31G) in the gas phase and in different solvents. Three different approaches, namely continuum, discrete, and hybrid (combined discrete/SCRF), were employed to investigate the effects of solvation on the tautomeric equilibria. In all cases, the neutral hydroxy form is significantly more stable than the zwitterionic oxo form (by 43-56 kJ mol(-)(1)) in the gas phase. The tautomeric energies reduce substantially in the presence of a polarizable dielectric medium. However, the neutral form is calculated to be the dominant form in nonpolar and aprotic polar solvents. On the other hand, a reversal of tautomeric equilibrium, in favor of the zwitterionic form, is predicted in an aqueous medium. This study highlights the role of both water molecules and bulk solvent effect in influencing the tautomeric equilibria of the PLP related compounds. A combination of explicit microsolvation and continuum reaction field is required to account fully for the energetic effect of aqueous solvation. The tautomeric free energy differences (deltaG(298)) of PLP in the gas phase and in aprotic polar (epsilon = 40) and aqueous media are predicted to be 47, 22, and -29 kJ mol(-)(1), respectively.     

Structure and ring-chain tautomerism of 2-hydroxy-5-methyl-3,4-benzocinnamaldehyde

The previously undescribed 2-hydroxy-5-methyl-3,4-benzocinnamaldehyde was synthesized. A cyclic 2-hydroxy-2H-chromene structure in the crystalline state and in nonpolar solvents was established for it by IR, UV, and PMR spectroscopy. It is shown that transition to a polar solvent leads to the establishment of a tautomeric ring-chain equilibrium, the position of which is determined by the type of solvent.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 610–613, May, 1982.     

Solvent Effect on The Equilibrium and Rate Constant of the Tautomeric Reaction in Nexium,Skelaxin, Aldara and Efavirenz Drugs: A Dft Study

Some drugs have two tautomeric structures in the liquid state and the tautomeric equilibrium is formed between these structures. The reaction rate and equilibrium constant of this reaction varies in different solvents. Thus, the determination of the appropriate solvent to separate tautomers is important. In this research, we used the DFT level of B3LYP and the 6-311++G** basis set to obtain the proper solvent for Nexium, Skelaxin, Aldara and Efavirenz drugs. All calculations were made above the melting point of the mentioned drugs, because these drugs are solid at room temperature. The solvent effect is included in the calculation utilizing the polarizable continuum model PCM. The transition state of the tautomeric reaction is determined using the quadratic synchronous transit (QST2) method. The geometry, energy, and dipole moment of transition states are analyzed in different solvent. The root mean square deviation (RMSD) analysis is performed to determine the degree of a structure deviation of tautomer 1 and tautomer 2 from the transition state in different solvents. It is found that the RMSD value for tatumer1 is higher than that for tautomer 2 in all studied drugs. The proper solvent for the separation of tautomers is determined from the analysis of thermodynamics and kinetics.     

Tautomerism of azine derivatives. Communication 10. Study of the tautomerism of pyrimidyl-2-cyanoacetic ester by the pmr method utilizing a “label of saturation” in the impulse variant

Conclusions The mechanism of the 1,5-prototropic interconversion of the ylidene tautomers of pyrimidyl-2-cyanoacetic ester was studied by the method of the transmission of inverted magnetization. It was shown that this process is accomplished by an ion-dissociation mechanism with the intermediate formation of the aromatic tautomeric form.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1166–1172, May, 1986.For Communication 9, cf. [I].     

Solvent and Structural Effects on the UV–Vis Absorption Spectra of Some 4,6-Disubstituted-3-Cyano-2-Pyridones

A series of 4,6-disubstituted-3-cyano-2-pyridones was synthesized and their UV?CVis absorption spectra were recorded in the region 200?C600?nm in the set of selected solvents. The effects of solvent dipolarity/polarizability and solvent?Csolute hydrogen-bonding interactions on the spectral shifts were analyzed by means of the linear solvation energy relationship concept of Kamlet and Taft. The influence of solvents as well as substituents on the 2-pyridone/2-hydroxypyridine tautomeric equilibration was evaluated. The absorption band maximum of the 2-hydroxypyridine form is found to appear at a shorter wavelength than that of the 2-pyridone form in all investigated solvents. The replacement of the methyl and phenyl groups at position 6 of the pyridone ring, by a hydroxy group, significantly changes the solvatochromic behavior of the investigated pyridones.     

The tautomerism of 5-chloro-2-hydroxypyridine. Comments on a paper by Srivastava and Prasad

Infrared and U.V. spectra are presented to show that 5-chloro-2-hydroxypyridine exists mainly in the pyridone form in solution in carbon tetrachloride, chloroform and cyclohexane, with extensive NH⋯OC intermolecular association at least in the former two solvents; in dioxane the pyridone and the pyridinol form are present in roughly equal amounts. As 2-pyridones are capable of forming centrosymmetric bimolecules of zero dipole moment, replacement of a highly polar solvent by a non-polar one does not necessarily displace the tautomeric equilibrium to predominance of the pyridinol tautomer, even though that has a much lower dipole moment than an individual 2-pyridone molecule. Some conclusions of Srivastava and Prasad's are questioned.     

The tautomerism of 6-hydroxy-, 6-amino- and 6-acylamino-7-azaindolines

The lactam-lactim tautomerism of 6-hydroxy-7-azaindolines and amino-imine tautomerism of 6-amino- and 6-acylamino-7-azaindolines has been studied by IR and UV spectroscopy. It is shown that the lactam-lactim tautomeric equilibrium of 6-hydroxy-7-azaindolines in contrast to the other analogous N-heteroaromatic compounds is not completely shifted for the lactam. The commensurable amounts of both tautomeric forms can be observed in the solutions of 6-hydroxy-7-azaindolines and it is possible to elucidate the influence of the solvent polarity upon the lactam-lactim tautomeric equilibrium. The tautomeric equilibrium of 6-amino- and 6-acylamino-7-azaindolines is practically completely shifted for the amino form, and even acylation with p-toluene-sulfonic acid does not result in a noticeable shift of the tautomeric equilibrium for the amino form in contrast to the other N-heterocyclic amines.     

Thermodynamic stability of 2,4,6-tris(nitromethyl)-1,3,5-triazine: an experimental and theoretical study

The molecular geometries and electronic structures of 2,4,6-tris(nitromethyl)-1,3,5-triazine isomers were investigated by the density functional method DFT/B3LYP/6-311++G** to elucidate the structural factors responsible for the stability of these systems. It was shown that a characteristic feature of the nitromethyl tautomer (1) of 2,4,6-tris (nitromethyl)-1,3,5-triazine consists in nonvalence interactions between an oxygen atom of nitro group and a carbon atom of triazine ring, which are probably due to Coulomb attraction between them. The tautomer with the 2,4,6-tris (nitromethylene)-hexahyrdo-1,3,5-triazine structure (2) is stabilized trough direct polar conjugation between the amino and nitro groups at the double bond. Structural strain of the molecule with the 2,4,6-tris(aci-nitromethyl)-1,3,5-triazine structure (3) is the reason for its thermodynamic instability. X-ray data indicate that the compound under study exists in the triazine tautomeric form 1 and the distances between oxygen atoms of nitro group and carbon atom of the triazine ring are shortened. NMR data suggest the existence of triazine in the nitromethyl form 1 in acetonitrile and acetone and a tautomeric equilibrium between the nitromethyl and nitromethylene forms in a more polar solvent (DMSO). The results obtained suggest a Coulomb-type stabilization of the 2,4,6-tris(nitromethyl)-1,3,5-triazine molecule in the gas phase, in the crystal, and in nonpolar solvents.