Keto-enol tautomerization reactions equilibria

Equilibrium Constants for Keto-Enol Tautomerization Reactions (K = enol]/[keto]) ... 

Interestingly, the product actually isolated from alkyne hydration is not the vinylic alcohol, or enol (ene + ol), but is instead a ketone. Although the enol is an intermediate in the reaction, it immediately rearranges to a ketone by a process called keto-enol tautomerisni. The individual keto and enol forms are said to be tautomers, a word used to describe constitutional isomers that interconvert rapidly. With few exceptions, the keto-enol tautomeric equilibrium lies on the side of the ketone enols are almost never isolated. We ll look more closely... 

Carbonyl compounds are in a rapid equilibrium with called keto-enol tautomerism. Although enol tautomers to only a small extent at equilibrium and can t usually be they nevertheless contain a highly nucleophilic double electrophiles. For example, aldehydes and ketones are at the a position by reaction with Cl2, Br2, or I2 in Alpha bromination of carboxylic acids can be similarly... 

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. 

Structural isomers existing in rapid equilibrium are tautomers and the equilibrium reaction is tautomerism. The above is a keto-enol tautomerism. 

The keto-enol tautomerism rates for oxaloacetate and zinc(II)-oxaloacetate have also been investigated using acetate buffer solutions.339,357 Thus for the equilibrium shown in equation (24) the value of fcf for the reaction oxacketI12 +OAc is 6.6x 10 3 M"1 s l, while for Zn(oxac)keto+ OAc , fcf= 25 M-1 s 1. The rate acceleration at 25 °C is ca. 4 x 103. Metal ion-promoted enolization is considered in detail in Section 61.4.20. 

Covey and Leussing330,357 have studied keto-enol tautomerism rates for oxaloacetate (oxac2-) and zinc(II) oxaloacetate complexes in acetate buffer solutions at 25 °C. Thus for the equilibrium oxacketo2 oxaceno,2- the value of fcf, the rate constant for the forward reaction, for the reaction oxacketo2 + OAc is 6.6 x 10 3 M-1 s 3 while for Zn(oxac)kcto) + OAc, kf is 25 M 1 s 1. The rate... 

Another approach used in the empirical characterization of liquid polarity is the study of the outcome of a chemical reaction. Earle et al. [216] report a preliminary study of the keto-enol tautomerization of pentane-2,4-dione, and create an empirical correlation between the degree of tautomerization and the dielectric constant of molecular liquids. They then predict dielectric constants for a series of ILs based on the observed keto-enol equilibrium the values range from 40 to 50, slightly higher than those of short-chain alcohols. A more detailed study by Angelini et al. [217] considers the tautomerization of a nitroketone complex in a series of five imidazolium-based ILs. The results, parameterized as a linear free energy analysis of the behavior of the equilibrium constant, indicates an overall polarity comparable to that of acetonitrile, consistent with the partitioning and spectroscopic studies referenced above. 

The initial product has a hydroxy group attached to a carbon-carbon double bond. Compounds such as this are called enols (ene + ol) and are very labile—they cannot usually be isolated. Enols such as this spontaneously rearrange to the more stable ketone isomer. The ketone and the enol are termed tautomers. This reaction, which simply involves the movement of a proton and a double bond, is called a keto—enol tautomerization and is usually very fast. In most cases the ketone is much more stable, and the amount of enol present at equilibrium is not detectable by most methods. The mechanism for this tautomerization in acid is shown in Figure 11.6. The mercury-catalyzed hydration of alkynes is a good method for the preparation of ketones, as shown in the following example ... 

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. 

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. 

It is also possible to induce aldol condensation reactions under acidic conditions. When 137 was treated with tosic acid in hot benzene (40-50°C), the normal keto-enol tautomerism equilibrium was shifted to favor enol 138. The enol attacked the carbonyl on the pyridone in an intramolecular aldol cyclization, producing aldol 139. Elimination of water under the reaction conditions gave an 84% yield of 140 in Comins synthesis... 

This case has already been illustrated (see paragraph 14.21.1.2.1.6.5). The skills of the chemist together with those of the analyst are needed to ensure that the presence of unexpected impurities can be detected. By way of example, the reactions involving the keto-enol tautomerism deserve to be mentioned. The equilibrium is very sensitive to the solvent so that the presence of other solvents as impurities in the main solvent can modify the keto-enol ratio leading to irreproducibility in the chemical process. 

The hydrogen atom of the 0-H group in enol 39 (also acidic) is attacked by the 7i-bond of the C=C unit the hydrogen atom is transferred to the carbon with cleavage of the 0-H bond, as shown in 39, to form the ketone (6). This reaction interconverts an enol and a ketone (the keto form in the equihbrium) however, the equilibrium strongly favors the keto form, and this process is called keto-enol tautomerism. The enol is said to tautomerize to the ketone. The carbonyl form is favored over the enol unless there is some special structural feature such as the presence of a second electron-withdrawing group on an a-carbon. Therefore, if an enol is formed in a chemical reaction, assume that it will tautomerize to the carbonyl form, which is the isolated product. 

Notice that the steps in the enol — acetaldehyde reaction are simply the reverse of the acetaldehyde — enol reaction (Fig. 19.15). Note also that in acid, as in base, aldehydes and ketones that have a hydrogens are in equilibrium with their enol forms. We will soon see that although enols are in equilibrium with the related keto forms, it is usually the keto forms that are favored. This equilibrium is called the keto-enol tautomerization.The carbonyl compound and its associated enol are called tautomers. 

Trifluoroacetylketene (91) has been generated in aqueous solution by flash photolysis. Rates of hydration to form the enol of 4,4,4-trifluoroacetoacetic acid (92e) have been measured, and also rates of the subsequent ketonization to the /3-keto acid (92k). Extensive rate and equilibrium constant data are reported for these reactions and for the ionizations of the tautomers. For example, the enol (92e) has acidity constants (in -logio form) of 1.85 and 9.95, for the acid and enol OH groups, respectively. Rates of enolization of (92k) have also been measured (by bromination) and, combined with an estimate of the hydration constant (K = 2900) of (92k), suggest that the keto-enol tautomeric constant is ca 0.5, about 100 times greater than that of its unfluorinated analogue. 

The keto-enol tautomeric equilibrium of acetylacetone is an intramolecular hydrogen exchange process. High-pressure NMR was used to study changes in this equilibrium over a pressure range to 2.5 kbar and temperatures to 145 C (51). With an increase in temperature at constant pressure, the equilibrium distribution shifted to the keto tautomer. An increase in pressure did not change the keto-enol distribution at any temperature. From the high-pressure experiments as a function of temperature the reaction enthalpy, A/J, and entropy, AS, were determined to be 2.80 0.02 kcal/mol and 7.2 0.3 cal/K mol, respectively. 

Reactions of Halogenation and Nitrosation Nitrones with protons in the a-alkyl group can occur in tautomeric nitrone-hydroxylamine equilibrium (Scheme 2.117) similar to keto-enol and imine-enamine tautomerisms. 

The review starts with a discussion of the mechanism of keto-enol tautomerisation and with kinetic data. Included in this section are results on stereochemical aspects of enolisation (or enolate formation) and on regioselec-tivity when two enolisation sites are in competition. The next section is devoted to thermodynamic data (keto-enol equilibrium constants and acidity constants of the two tautomeric forms) which have greatly improved in quality over the last decade. The last two sections concern two processes closely related to enolisation, namely the formation of enol ethers in alcohols and that of enamines in the presence of primary and secondary amines. Indeed, over the last fifteen years, data have shown that enol-ether formation and enamine formation are two competitive and often more favourable routes for reactions which usually occur via enol or enolate. 

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