Keto-enol tautomerism, solvent effect

Like reaction rates, the effect of solvent polarity on equilibria may be rationalized by consideration of the relative polarities of the species on each side of the equilibrium. A polar solvent will therefore favour polar species. A good example is the keto-enol tautomerization of ethyl acetoacetate, in which the 1,3-dicarbonyl, or keto, form is more polar than the enol form, which is stabilized by an intramolecular H-bond. The equilibrium is shown in Scheme 1.3. In cyclohexane, the enol form is slightly more abundant. Increasing the polarity of the solvent moves the equilibrium towards the keto form [28], In this example, H-bonding solvents will compete with the intramolecular H-bond, destabilizing the enol form of the compound. 

Scheme 1.3 The effect of solvent polarity on keto-enol tautomerization of ethyl acetoacetate...

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

Even for a simple reaction, involving just one reactant species and one product species, such as a keto-enol tautomerism or a cis-trans isomerization, the above equation for a given solvent is complicated. StUl, in specific cases it is possible to unravel the solvent effects of cavity formation, for the solute species have different volumes, polarity/polarizability if the solute species differ in their dipole moments or polarizabilities, and solvent Lewis acidity and basicity if the solutes differ in their electron-pair and hydrogen-bond acceptance abilities. 

Isomer stabilities and activation energies have been calculated for keto-enol tautomerization of simple carbonyl compounds, MeC(R)=X (X = O R = H, Me) 129 both specific and bulk solvent effects have been analysed. Related isomerizations of acid derivatives (R = F, CN) and other related structures (R = H X = CF12, NH, S) are compared. 

Solvent and concentration effects on keto-enol tautomerization have been investigated in DMSO-water mixtures and aqueous micellar solutions, for 2-acetylcyclo-hexanone and 2-acetyl-1-tetralone.286 Dramatic rate increases aboves 60% DMSO content have been explained in terms of solvent structure solvent polarity alone cannot rationalize the effect. 

Solvent Effects on Tautomeric Equilibria 4.3.1 Solvent Effects on Keto/Enol Equilibria [36-43,134]... 

Solvent effects similar to those described for the keto/enol equilibria can also be found for other tautomerisms, e.g. lactim/lactam, azo/hydrazone, ring/chain equilibria, etc. [62-64], The pecularities arising here can only be illustrated by means of a few representative examples. 

Figure 1.9 Solvent polarity effect on a keto-enol tautomerization.

The effect of solvent polarity on chemical systems including reaction rates and equilibria can be quite significant. In general, it is necessary to consider the relative polarities of the reactants and products. In equilibria, a polar solvent will favour the more polar species. A good example is the keto-enol tautomerization of ethyl acetoacetate shown in Figure 1.9. The keto tautomer is more polar than the enol tautomer and therefore the equilibrium lies to the left in polar media such as water Table 1.11. 

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 solvent polarity, which is defined as the overall solvation capability of a liquid derived from all possible, non-specific and specific intermolecular interactions between solute and solvent molecules [4], cannot be represented by a single value encompassing all aspects, but constants such as the refractive index, the dielectric constant, the Hildebrand solubility parameter, the permanent dipole moment, the partition coefficient logP [5] or the normalised polarity parameter TN [6] are generally employed to describe the polarity of a medium. The effect of a solvent on the equilibrium position of chemical reactions, e.g. the keto-enol tautomerism, may also be used. However, these constants reflect only on some aspects of many possible interactions of the solvent, and the assignment to specific interactions is difficult if not impossible. 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl... 

Heteroarylthiols react quickly with conjugated azoolefins to afford a-heteroarylthiohydrazones by the usual 1,4-addition of the thiol to the heterodiene system. The treatment of the latter compounds with sodium methoxide, and then with trifluoroacetic acid provides mainly regioisomeric 4-heteroarylthio-l//-pyrazol-5(2f/)-ones in good yields by an heterocyclization process with the loss of an alcohol molecule. These reactions can be succesfully executed in a one-pot procedure (Scheme 12). A detailed iH- and J3c-NMR study of these compounds in OMSO-d shows a solvent effect on the enol-keto tautomerism, often with conversion of the keto into the enol form. X-Ray diffraction determination demonstrates unambiguously that these compounds exist in... 

The keto-enol tautomerization of acetylacetone (CH3-CO-CH2-CO-CH3), a prototype /3-diketone, has been extensively studied experimentally, and attention has been paid to its solvent effect. Although the enol form is more stable than the keto in the gas phase owing to the intramolecular hydrogen bonding, the equilibrium is known to shift toward the keto in solution as the solvent polarity increases. The tautomerization in various types of solution, which includes H2O, dimethyl sulfoxide (DMSO), and carbon tetrachloride (CCI4), was examined by means of RISM-SCF method. [18]... 

The only isotope effects which are usually of significance in electroorganic mechanism considerations are those involving H and D in (a) primary kinetic isotope effects, (b) secondary solvent isotope effects where reactions are compared in pure H2O and D2O or pure h- and rf-alcohols, and (c) in prior protonation equilibria, e.g., with ketone reduction. Primary kinetic isotope effects having a magnitude of > 2.5 may be expected in reactions that involve a rearrangement with proton participation, e.g., keto-enol tautomerism prior to an electron transfer step. Most other H/D isotope effects arise from protonation equilibria prior to the rate-controlling electron transfer step (e.g., in ketone reduction RR CO + RR COH ) and the isotope effect is... 

A polar solvent like water is known to have a relevant influence on the covalent structure of polar molecules. This is clearly illustrated by the effect of hydration on the tautomeric equilibria of molecules. A prototypical example is the keto/enol equilibrium of P-diketones whereas the enol form is the most populated species in the gas phase and in apolar solvents, the keto form is the most stable tautomer in aqueous solution [106,107]. Inspection of Figure 5 allows us to rationalize the solvent-induced change in the topology of this molecule. 

Ferrari, E., Saladini, M., Pignedoli, F., Spagnolo, F., and Benassi, R. (2011) Solvent effect on keto-enol tautomerism in a new 3-diketone a comparison between experimental data and different theoretical approaches. New J. Chem., 35, 2840-2847. 

Keto-Enol Tautomerism in 4-(phenyldiazenyl)naphthalen-l-ol Solvent Effect... 

The effect of LiFOS on micellization of 6ED was investigated by keto-enol tautomerism of benzoylacetanilide (BZAA) [126]. BZAA exists in the enol form in 6ED solutions above the cmc. The enolization in the hydrocarbon chain surfactant solution is similar to that in organic solvents. In aqueous solutions of LiFOS, enolization was not observed. The enolic absorbance of BZAA at 315 nm above the cmc of 6ED decreases when LiFOS is added and the absorbance of the keto tautomer at about 250 nm increases. This result was explained by mixed-micelle formation and the existence of a limited number of sites in the micelle which BZAA or LiFOS could occupy. 

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