Ethyl acetoacetate keto-enol equilibrium

Ethers, reactions of, 315, 671, 1067, 1068 see also under Aliphatic ethers and Aromatic ethers. p-Ethoxyphenylurea, 646 p-Ethoxyproptonitrile, 915,916 Ethyl acetate, 383 purificatioh of. 174 Ethyl acetoacetate, 475, 476, 477 keto-enol equilibrium of, 475, 1148 purification of, 478 reactions of, 478 ... 

The addition of comparatively less polar alcohols to solutions of acetylacetone in water shifts its keto/enol equilibrium in favour of the less polar m-enolic form (4b), which has been quantitatively rationalized in terms of so-called pairwise solute/solvent interactions [245], The keto/enol equilibrium of ethyl acetoacetate and acetylacetone has also been studied in polar supercritical fluids such as CHF3 (//= 1.65 D) and CCIF3 [fi = 0.50 D) [246], In polar trifluoromethane, the dipolar keto form was found to be favoured, although the change in the equilibrium constant with increasing sc-fluid density [i.e. increasing pressure) was quite minor. For ab initio calculations of the relative stabilities of various enols of acetylacetone in the gas phase, and theoretical calculations of keto/enol equilibria in aqueous solutions, see references [247] and [248], respectively. 

The keto-enol equilibrium constants of acetylace-tone, ethyl acetoacetate and ethyl benzoylacetate in water at 25°C were determined by studying the influence of surfactants on their UV-visible spectra. These measured equilibrium constants were used to obtain the reactivity of the ketones towards several nitrosating agents. 

Ethyl acetoacetate is a tautomeric substance which at room temperature exists as an equilibrium mixture of the keto and enol forms, the latter form being present to the extent of about 7%. 

If the refractivity of the pure tautomeric constituents is known, the composition of the equilibrium mixture can be determined. This method has been used to study, for example, the keto and enol tautomers of ethyl acetoacetate. So far it has not been applied to heterocyclic compounds in this series the isolation of the pure... 

Experiment.—About 0-5 c.c. of ethyl acetoacetate is dissolved with shaking in the necessary amount of water, a few drops of ferric chloride solution are added, and to the cold solution dilute (1 10) bromine water is added, drop by drop, but rather quickly from a tap funnel, until the red colour of the ferric enolate has disappeared. The enol has now been completely used up by the bromine, but since, in order to restore the equilibrium, more enol is formed, the colour reappears after a short time and can at once be destroyed again by the addition of a few drops of bromine. The procedure can be repeated until the whole of the ethyl acetoacetate is converted into ethyl bromoacetoacetate. By means of this experiment the keto-... 

The ratio in which the keto- and enol-forms are present at equilibrium is greatly dependent on the nature of the solvent. The following table gives figures for ethyl acetoacetate ... 

Experiment.—Ethyl acetoacetate (2-5 g.) is dissolved in 20 c.c. of 2V-alkali hydroxide solution, the solution is cooled in ice to 0° and 20 c.c. of cooled -hydrochloric acid are added in one lot, with shaking. A turbid milky solution is formed which, however, becomes clear in a few seconds. The enol, which is less soluble in water than the keto-form, at first separates, but changes very rapidly and almost completely into the more soluble keto-form, as the conditions of the equilibrium in water require. 

It has also been possible, in various ways which cannot be detailed here, to prepare both the keto- and enol-forms of ethyl acetoacetate in the pure state (Knorr, K. H. Meyer). Their physical constants are altogether different. The refractive index, for example, is 1-4225 (D10 ) for the keto-form and 1-4480 for the enol-form. From determinations of the refractive indices of equilibrium mixtures the content of both forms can be calculated by interpolation (Knorr, 1911), and these results have been confirmed spectroscopically (Hantzsch, 1910). 

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. 

Keto-enol tautomerism equilibrium of ethyl acetoacetate at ca. 20°C. 

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. 

Whenever two or more readily interconvertible isomers of a substance are in (dynamic) equilibrium, there will generally be migration of double bonds. The most often encountered tautomerism is between the keto and tire enol forms of an oxygen-containing compound. Ethyl acetoacetate is probably one of the earliest known cases of keto-enol tautomerism. While the keto-form, XXH, shows a low intensity (e 20) band around 275 mp characteristic of an isolated keto-carbonyl group, the enol form, XXIII, shows a high intensity band (< 18,000) around 245 mp due to the conjugated double... 

Step 3 drives the equilibrium forward. In this step, the /1-keto ester is converted to its enolate anion. The methylene (CH2) hydrogens in ethyl acetoacetate are a to two carbonyl groups and hence are appreciably more acidic than ordinary a-hydrogens. They have a of 12 and are easily removed by the base (ethoxide ion) to form a resonance-stabilized -keto enolate ion, with the negative charge delocalized to both carbonyl oxygen atoms. 

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