Keto-enol tautomerism acetoacetate

Space does not permit any further detailed discussion except for a brief account of two interesting subjects. The first is concerned with keto-enol tautomerism. The classical example is ethyl acetoacetate, which can exist in the keto form (I) and the enol form (II) ... 

At the end of the war, he returned to Munich as Associate Professor and Director of the Laboratory of Organic Chemistry. The Department was then under Richard Willstatter s direction, and Meyer occupied the same position as the one held for many years by Willstatter under Baeyer s leadership. He resumed his investigation on keto-enol tautomerism, and, in collaboration with H. Hopff, isolated by distillation the pure enol form of ethyl acetoacetate. Other work from the same period included an examination of the action of nitric acid on phenol and phenol ether (with W. Reppe and W. E. Elbers), and a study of narcosis (with H. G. Billroth)— an extension of his father s work. 

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...

Keto-enol tautomerism of fi-keto esters can be analyzed by carbon-13 NMR as illustrated by an inverse gated proton-decoupled 13C NMR spectrum of ethyl acetoacetate in Fig. 4.6 [73 i]. 

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. 

Raman effect was to keto-enol tautomerism. Thus in the case of acetoacetic ester, a characteristic frequency corresponding to that of the G=G bond is observed. In the keto form, CH3COCH2COOG2H5, such a bond does not occur, nor does such a bond exist in the hydrolysis products (acetone, CH3GOGH3 and ethyl acetate, GH3GOOG2H6) presence of this frequency shows that in... 

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... 

Figure 10.49. A comparison of (a) the conventional ID spectrum of ethyl acetoacetate (60 pmol, 3000 scans, 400 MHz) with (b) the DNP-enhanced spectrum (bOpmol, single scan, 400 MHz). The resonance labelled with an asterisk is missing in trace (a) due to deuteration of the centre as a result of keto-enol tautomerism see text (data courtesy of Oxford Instruments Molecular Biotools).

Some of the chelate compounds can act as dienophilic reagents, decomposing polyene structures formed as a result of dehydrochlorination of the polymer [24]. Compounds of calcium with 1,3-dicarbonyl derivatives, capable of keto-enol tautomerism, for example, with the ethyl ester of acetoacetic acid [199], have been proposed for the stabilization of polyvinyl chloride ... 

Keto-enol tautomerism encountered in ethyl acetoacetate (Figure 3.40) is another slow exchange process. It results in a small contribution of the enol tautomer of ethyl acetoacetate to the spectrum, the enol form being partly stabilized due to conjugation of the double bond of the enol with the a-carbonyl group of the ester moiety. 

Figure 3.40. Keto-enol tautomerism in ethyl acetoacetate.

Acetoacetic ester can exist in both the keto and enol tautomeric forms and it might be expected that the enol form would have a higher boiling point and would dissolve more readily in water, than the keto form. This is not the case, however, and the enol form has the lower boiling point and dissolves in water approximately twenty times less readily than the keto form. This behaviour is explained by the formation of a hydrogen bond in the enol form as in structure /,... 

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%. 

Ethyl malonate, like ethyl acetoacetate, exists as a tautomeric mixture of keto and enol forms, although in the case of ethyl malonate... 

The proposed mechanism for the Conrad-Limpach reaction is shown below. Condensation of an aniline with a 3-keto-ester (i.e., ethyl acetoacetate 5) with loss of water provides enamino-ester 6. Enolization furnishes 10 which undergoes thermal cyclization, analogous to the Gould-Jacobs reaction, via 6n electrocyclization to yield intermediate 11. Compound 11 suffers loss of alcohol followed by tautomerization to give 4-hydroxy-2-methylquinoline 7. An alternative to the proposed formation of 10 is ejection of alcohol from 6 furnishing ketene 13, which then undergoes 671 electrocyclization to provide 12. 

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... 

For acetoacetic ester, the mystery lay in the two rather different forms the "ester" took the so-called enol (hydroxy) form CH3C(OH) = CH-COOC2H5 and the keto (ketone) form CH3COCH2COOC2H5.37 (See fig. 6.) As mentioned briefly in chapter 5, in 1885, Laar at Bonn coined the word "tautomerism" for the behavior of acetoacetic ester, (tautos, the same meros, part), hypothesizing that the phenomenon of two structures in one is due to a continual oscillation of a hydrogen atom between two positions in the molecule, with an accompanying change in the bonds between the atoms. Of course, this hypothesis appears to have been influenced by Kekule s earlier mechanical hypothesis. 

Also termed ethyl acetoacetate, or CH3COCH2COOC2-H5. As an ester, it can be hydrolyzed under certain conditions to acetoacetic acid (CH3COCH2COOH) as a ketone, it reacts with reagents for the carbonyl (C = O) group. Peculiarly, it also behaves like a hydroxyl (OH-) compound. It is the prototype of the phenomenon of tautomerism, and its isomeric forms are termed the keto and the enol forms. 

The chemical properties of acetoacetic ester are those of a ketone and an ester. It contains, however, a small proportion of the tautomeric enol form of the compound, as a color is produced when it is treated with ferric chloride. The ester dissolves in alkalies owing to the formation of a soluble sodium salt. It is believed that the salt is formed as the result of the interaction of the alkali with that part of the ester which has the enol structure, As the latter is removed in this way the keto form undergoes rearrangement to the enol form in order to establish the normal equilibrium between the two forms. The change continues until, in the end, the ester dissolves completely. When an aqueous solution of the sodium salt of acetoacetic ester is treated with an acid, the enol form of the ester is first precipitated in drops these slowly disappear as a result of their transformation into the keto form provided enough water is present. The solubility of the enol form in water is much less than that of the keto form (0.5 per cent and 11 per cent, respectively, at 0°). 

The decarboxylation of acetoacetic acid, a P-keto acid, occurs by way of a cyclic transition state in which a proton is transferred from the carboxylate atom to the carbonyl oxygen to give an enol that rapidly tautomerizes to give acetone. 

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