Tautomeric equilibria, solvent effects

Thermochemical investigations of tautomeric equilibria solvent effects... 

Adamo, C., and F. Lelj. 1994. Equilibrium solvent effects in the framework of density functional theory. Application to the study of the thermodynamics of some organic and inorganic tautomereic equilibria. Chem. Phys. Lett. 223, 54. 

The several theoretical and/or simulation methods developed for modelling the solvation phenomena can be applied to the treatment of solvent effects on chemical reactivity. A variety of systems - ranging from small molecules to very large ones, such as biomolecules [236-238], biological membranes [239] and polymers [240] -and problems - mechanism of organic reactions [25, 79, 223, 241-247], chemical reactions in supercritical fluids [216, 248-250], ultrafast spectroscopy [251-255], electrochemical processes [256, 257], proton transfer [74, 75, 231], electron transfer [76, 77, 104, 258-261], charge transfer reactions and complexes [262-264], molecular and ionic spectra and excited states [24, 265-268], solvent-induced polarizability [221, 269], reaction dynamics [28, 78, 270-276], isomerization [110, 277-279], tautomeric equilibrium [280-282], conformational changes [283], dissociation reactions [199, 200, 227], stability [284] - have been treated by these techniques. Some of these... 

For some compounds NMR data were collected to determine the equilibrium constants for the tautomerism between the azide form such as for 30 and the tetrazole derivative 31 (Scheme 3). Similar investigations were conducted for the compounds 28 and 29 and the solvent effects and substituent effects are discussed <1996JHC747>. 

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]. 

In 5-hydroxy-3-phenyl-l,2,4-oxadiazole (97a) the keto forms (97b, c) predominate due to the proximity of the electronegative oxygens at the sp2 carbon. Of these three tautomers (97c) is favored by IR, UV and NMR spectral data (76BSB35). The tautomer (98b) is more important in the 5-phenyl isomer in solution. Nevertheless the position of tautomeric equilibrium in the two cases is dependent on solvent. For example, in the solid (98b, c) predominates but in acetone and other oxygen solvents (98a) allows for an effective hydrogen bonded dimer (99). 

Nitroimidazole in solution (amphiprotic medium) is stabilized as the 5-nitro isomer due to formation of hydrogen bond with an aprotic protophilic solvent [1124], The medium favors displacement of the tautomeric equilibrium toward the 4-nitro isomer via formation of a solvate complex at the same time 4-nitroimi-dazole acts as hydrogen-bond acceptor. The specific solvatochromic effect in the UV spectrum of 4-nitroimidazole is caused by the electronic configuration of the excited jr,ji -state [1124],... 

Neglecting solvent effects is extremely hazardous. Equilibria and kinetics can be dramatically altered by the nature of the solvent For example, the rate of nucleophilic substitution reactions spans 20 orders of magnitude in going from the gas phase to polar and nonpolar solvents. A classical example of a dramatic solvent effect on equilibrium is the tautomerism between 1 and 2. In the gas phase, the equilibrium lies far to the left, while in the solution phase, 2 dominates because of its much larger dipole moment." Another classical example is that the trend in gas-phase acidity of aliphatic alcohols is reverse of the well-known trend in the solution phase in other words, in the solution phase, the relative acidity trend is R3COH < R2CHOH < RCH2OH, but the opposite is true in the gas phase. ... 

Methylimidazolin-4-ones can exist in three possible forms (38-40 X = 0) (Scheme 16). In the solid state, l,2-dimethyl-5-phenylimidazolin-4-one exists in the OH form (39 X = 0), but insolubility precluded studies in solution. Compounds stated to be 1-acyl-imidazolin-4-ones have been formulated as the 4-oxo forms (analogous to 38 X = O) on IR evidence. Where possible, it seems that a non-conjugated carbonyl form (e.g. 34, 42 X = O) is preferred to the conjugated version (e.g. 37,41 X = O), but although substituents may have a marked effect, the nature of the solvent is not of particular importance in determining the position of tautomeric equilibrium for these compounds. 

Azides and tetrazoles usually equilibrate slowly at room temperature and the position of the equilibrium, which varies with temperature and solvent, is also susceptible to steric and electronic effects, electron-withdrawing substituents favouring the azide tautomer. The azinyl-azide/tetrazole tautomeric equilibrium, which has been extensively investigated and reviewed [9, 10], also arises when the C = N double bond comprises part of a heterocyclic ring, as exemplified by 2-azidoadenosine (5a, R = J3-d-ribofuranosyl) synthesized for use, as the diphosphate, as a photoaffinity reagent for the ADP receptor [11]. The azide was found to equilibrate with one or both of the two possible tetrazoles (5b and 5c) with an azide. tetrazole ratio of 1 1 at pH 7.0, and in contrast to the azide, which was readily photolyzed at 270nm, the tetrazole tautomer was resistant to photolysis. Azides that exist predominantly as tetrazoles may thus exhibit different... 

In 1906, at the age of twenty-nine, Hibbert came to the United States on a two-year appointment at Tufts College, in Boston, Massachusetts. There he worked under Professor Arthur Michael on keto-enol tautomerism and the effect of solvent on the equilibrium. Hibbert s association with Michael, with whom he published some half-dozen papers, was to have a profound and lasting influence on his subsequent career,... 

The Monte Carlo method can also be used to study the effect of solvent on the position of tautomeric equilibrium (Metropolis et al., 1953). This method models a dilute solution as N solvent molecules (N — 102) and 1 solute molecule. The fundamental requirement for a Monte Carlo simulation of tautomer solvation is a set of pair potentials for the solvent-solvent and solvent-solute interactions because approximately 106 config-... 

It should be noted that the keto-enamine tautomers of Schiff bases are observed always when the latter are derived from 2-hydroxynaphthaldehyde and aniline. However, in Schiff bases derived from salicylaldehyde and aniline, the new band at >400 nm in UV-Vis spectra was not observed in both polar and non-polar solvents, but it appeared in acidic media. In this workl which contains a quite good survey of the investigations of tautomerism in Schiff bases, the effects of the solvent polarity and acidic media on the phenol-imine keto-amine tautomeric equilibrium in systems 55 and 56 were reported. It was shown by H NMR and UV-Vis spectra that compound 55 is in tautomeric equilibrium of structures 55a and 55b in both polar and non-polar solvents (equation 17), whereas the tautomer 56b was not observed for compound 56 (equation 18) . ... 

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