Keto-enolic equilibrium

A ketone exists in equilibrium with its enol tautomer. You were introduced to tautomers in Section 6.6. Recall that tautomers are isomers that are in rapid equilibrium. Keto-enol tautomers differ in the location of a double bond and a hydrogen. 

Polar solvents shift the keto enol equilibrium toward the enol form (174b). Thus the NMR spectrum in DMSO of 2-phenyl-A-2-thiazoline-4-one is composed of three main signals +10.7 ppm (enolic proton). 7.7 ppm (aromatic protons), and 6.2 ppm (olefinic proton) associated with the enol form and a small signal associated with less than 10% of the keto form. In acetone, equal amounts of keto and enol forms were found (104). In general, a-methylene protons of keto forms appear at approximately 3.5 to 4.3 ppm as an AB spectra or a singlet (386, 419). A coupling constant, Jab - 15.5 Hz, has been reported for 2-[(S-carboxymethyl)thioimidyl]-A-2-thiazoline-4-one 175 (Scheme 92) (419). This high J b value could be of some help in the discussion on the structure of 178 (p. 423). 

Enols are related to an aldehyde or a ketone by a proton transfer equilibrium known as keto-enol tautomerism (Tautomensm refers to an mterconversion between two struc tures that differ by the placement of an atom or a group)... 

Certain structural features can make the keto-enol equilibrium more favorable by stabi hzmg the enol form Enolization of 2 4 cyclohexadienone is one such example... 

Many nitrogen containing compounds engage in a proton transfer equilibrium that is anal ogous to keto-enol tautomensm... 

As it is well known, 2,4-dihydroxyfurans 43 (tetronie aeids) exist as equilibrium mixtures of keto-enol 44 and dioxo forms 45. 

Dialkyl-3-hydroxyselenophenes exist in a keto-enol equilibrium 82 83 (72CS9). Analysis of the ionization potentials showed that for these compounds both the keto and the enol form are important [75ACS(B)652]. 

The amino form is usually much more favored in the equilibrium between amino and imino forms than is the hydroxy form in the corresponding keto-enol equilibrium. Grab and XJtzinger suggest that in the case of a-amino- and a-hydroxy-pyrroles, structure 89 increases the mesomeric stabilization and thus offsets the loss of pyrrole resonance energy, but the increase due to structure 90 is not sufficient to offset this loss. Similar reasoning may apply to furans and... 

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... 

Enolizable compounds can be used for Meerwein reactions provided that the keto-enol equilibrium is not too far on the side of the ketone for example, P-dicar-bonyl compounds such as acetylacetone are suitable (Citterio and Ferrario, 1983). The arylation of enol esters or ethers (10.12) affords a convenient route for arylating aldehydes and ketones at the a-carbon atom (Scheme 10-48). Silyl enol ethers [10.12, R = Si(CH3)3] can be used instead of enol ethers (Sakakura et al., 1985). The reaction is carried out in pyridine. 

For a review of keto-enol equilibrium constants, see Toullec, J. in Rappoport, Ref. 314, p. 

The tautomeric equilibrium between enols and ketones or aldehydes is not normally a preparative reaction, though for some ketones both forms can be prepared (see p. 75 for a discussion of this and other aspects of tautomerism). For most ketones and aldehydes only the keto form is detectable under ordinary conditions, though the equilibrium must occur, since aldehydes and ketones often react through their enol forms. 

An additional example of cycloamylose-induced catalysis which can probably be attributed to a microsolvent effect is the oxidation of a-hy-droxyketones to a-diketones (Scheme VIII). The rate of this oxidation is accelerated by factors ranging from 2.1 to 8.3 as the structure of the substrate is varied. As noted by Cramer (1953), these accelerations may be attributed to a cycloamylose-induced shift of the keto-enol equilibrium to the more reactive enol form. 

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. 

In addition to heterocycles, other molecular systems have attracted theoretical attention with respect to prediction of tautomeric equilibria and solvation effects thereon. The most commonly studied example in this class is the equilibrium between formamide and formamidic acid, discussed in the next section. In addition, some continuum modeling of solvation effects on keto/enol equilibria have appeared these are presented in section 4.2.2.2. We note that the equilibrium... 

Regarding the first problem, the most elemental treatment consists of focusing on a few points on the gas-phase potential energy hypersurface, namely, the reactants, transition state structures and products. As an example, we will mention the work [35,36] that was done on the Meyer-Schuster reaction, an acid catalyzed rearrangement of a-acetylenic secondary and tertiary alcohols to a.p-unsaturatcd carbonyl compounds, in which the solvent plays an active role. This reaction comprises four steps. In the first, a rapid protonation takes place at the hydroxyl group. The second, which is the rate limiting step, is an apparent 1, 3-shift of the protonated hydroxyl group from carbon Ci to carbon C3. The third step is presumably a rapid allenol deprotonation, followed by a keto-enol equilibrium that leads to the final product. 

Alternatively, the synthesis may begin by condensing aniline with the l-chloro-2-carboxy intermediate. Acridone vat dyes of this type have excellent light fastness but only moderate resistance to alkali due to the keto-enol equilibrium. It is interesting that this pentacyclic dye is approximately 30 nm more bathochromic than the closely related tetracyclic 1-amino-2-benzoylanthraquinone. 

The keto/enol ratio in organotin enolates is dependent on the enol structure and on the environmental conditions, a good ligand for the tin shifting the equilibrium toward the enolate, and increasing its reactivity (Equation (142)).392... 

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-... 

In respect of their properties, conditions of rearrangement, and reactions, we simply refer to what was said about the keto-enol change. Here, also, the bromine method enables the points of equilibrium to be determined quantitatively. The oldest and most important example of desmotropy in nitro-compounds was found in phenylnitromethane,... 

Fig. 6 The 2-(2-hydroxyphenyl)benzothiazole (HBT) unit that represents the keto-enol equilibrium (tautomerism). Normally, the enol (keto) form is rather stable in the ground state (in the excited state), respectively...

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. 

The bifluoride ion, HFj 297 Strong hydrogen bonding in p-diketones 309 Keto/enol equilibrium 310 Structures 312 Hydrogen-bond energies 314 Vibrational modes 315 Nmr spectroscopy 317... 

The keto/enol equilibrium (15) has been a spur to much research. In the absence of catalysts the equilibrium is established slowly and is very sensitive to a variety of influences, both internal, such as the nature of a- and P-substituents, and external, such as temperature and solvent. The discovery that the equilibrium was established sufficiently slowly to permit both keto and enol tautomers to be observed by H-nmr spectroscopy allowed these several influences to be easily investigated (see Kol tsov and Kheifets, 1971, for a review of the early work, and Emsley, 1984, for later work). 

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