Keto-enol interconversion

Enols aie related to an aldehyde or a ketone by a proton-transfer equilibrium known as keto-enol tautomerism. (Tautomerism refers to an interconversion between two structures that differ by the placement of an atom or a group.)... 

A carbonyl compound with a hydrogen atom on its a carbon rapidly equilibrates with its corresponding enol (Section 8.4). This rapid interconversion between two substances is a special kind of isomerism known as keto-enol tautomerism, from the Greek Canto, meaning "the same," and meros, meaning "part." The individual isomers are called tautomers. 

Au/C was established to be a good candidate for selective oxidation carried out in liquid phase showing a higher resistance to poisoning with respect to classical Pd-or Pt-based catalysts [40]. The reaction pathway for glycerol oxidation (Scheme 1) is complicated as consecutive or parallel reactions could take place. Moreover, in the presence of a base interconversion between different products through keto-enolic equilibria could be possible. 

Simplifications ease the extraction of accurate values for the rate constants. For example, the keto, enol interconversion may sometimes be ignored, and k 2 > Xc, and Xtj > k are justifiable assumptions. ... 

Many of the compounds that undergo ready base-catalysed keto < enol prototropic changes, e.g. ) -keto esters, l,3-( -) diketones, aliphatic nitro compounds, etc., form relatively stable carbanions, e.g. (25), that can often be isolated. Thus it is possible to obtain carbanions from the keto forms of the -keto ester (23a) and nitromethane (24a) and, under suitable conditions, to protonate them so as to obtain the pure enol forms 23b) and (24b), respectively. It thus seems extremely probable that their interconversion follows the intermolecular pathway (a). The more acidic the substrate, i.e. the more stable the carbanion to which it gives rise, the greater the chance that prototropic interconversion will involve the carbanion as an intermediate. 

Hydroxyaminobenzo-furan and -thiophene (32a X = O, S) are the unstable enam-ine tautomers of the corresponding oximes (32b). Kinetics of the tautomeric interconversions have been measured, yielding tautomeric constants the latter have been compared with the corresponding keto-enol constants. The enamines are ca 40 times less stable, relative to the oximes, than are the enols, relative to the ketones. The minor tautomers are ca 100 times more stable (relative to the major) for the benzothiophene system. 

The interconversion of keto and enol forms is termed enolization, or keto-enol tautomerism. The... 

There is a distinct relationship between keto-enol tautomerism and the iminium-enamine interconversion it can be seen from the above scheme that enamines are actually nitrogen analogues of enols. Their chemical properties reflect this relationship. It also leads us to another reason why enamine formation is a property of secondary amines, whereas primary amines give imines with aldehydes and ketones (see Section 7.7.1). Enamines from primary amines would undergo rapid conversion into the more stable imine tautomers (compare enol and keto tautomers) this isomerization cannot occur with enamines from secondary amines, and such enamines are, therefore, stable. 

Many simple organic compounds exist as mixtures of two or more rapidly interconvertible isomers or tautomeric forms. Tautomers can sometimes be separated one from the other at low temperatures where the rate of interconversion is low. The classic example is the oxo-enol (or keto-enol) equilibrium (Eq. 2-1). 

The second main aspect of reactions of carbonyl compounds is one we have already touched upon in Chapter 3. The carbonyl group increases the acidity of C—H bonds on a carbon directly attached to it by many powers of ten over an unactivated carbon-hydrogen bond. Removal of such a proton leaves the conjugated ambident enolate ion (29), which can be reprotonated either at the carbon, to give back the original keto tautomer, or at oxygen to give the enol (Equation 8.61).135 Acid also promotes interconversion between enol and keto... 

The enol tautomers of many ketones and aldehydes, carboxylic acids, esters and amides, ketenes, as well as the keto tautomers of phenols have since all been generated by flash photolysis to determine the pH rate profiles for keto-enol interconversion. Equilibrium constants of enolization, KB, were determined accurately as the ratio of the rate constants of enolization, kE, and of ketonization, kK, Equation (1). 

We note that for the case of keto/enol interconversion, it is simple, useful and remarkably accurate to equate the difference of Gibbs energies in aqueous media of the two tautomers and the difference of enthalpies of formation in the gas J. R. Keefe and A. J. Kresge, J. Phys. Org. Chem., 5, 575 (1992). We are pleased. 

Considerations of entropies of activation played a major role in a recent discussion of the acid-catalyzed interconversion of 1,2-cyclo-hexanedione and its enol (Bakule and Long, to be published). The reaction is more complex than the usual keto-enol interconversion because the ketone form, but not the enol, is found to be hydrated. 

The complex is additionally stabilised by co-ordination of the phenoxide, and possibly the carboxylate, to the metal ion, illustrating the utility of chelating ligands in the study of metal-directed reactivity. We saw in the previous section the ways in which a metal ion may perturb keto-enol equilibria in carbonyl derivatives, and similar effects are observed with imines. The metal ion allows facile interconversion of the isomeric imines. The first step of the reaction is thus the tautomerisation of 5.28 to 5.29 (Fig. 5-56). Finally, the metal ion may direct the hydrolysis of the new imine (5.29) which has been formed, to yield pyridoxamine (5.30) and the a-ketoacid (Fig. 5-57). 

Recently, the present author (Toullec and Verny-Doussin, 1980) obtained a concordant value for the equilibrium constant of (65 L = H) for [83, n — 3] from kinetic data on amine-catalysed iodination of acetone at low iodine concentrations. The principle of this determination is similar to that described for estimation of the keto-enol equilibrium constants by the kinetic halogenation method (see p. 48). At low iodine concentrations ( 10-6 mol dm-3), the enamine pathway is preferred [see (61)] and iodination of the enamine is rate-limiting. Rate measurements, in a pH range in which only the monoprotonated and diprotonated forms of the diamine exist, made it possible to determine the second-order rate constants k u which include the equilibrium constants, for interconversion of the ketone and protonated enamine... 

As Section IV will be mostly devoted to 2,4-pentanedione, acacH, it is worthwhile to dwell on this well studied species. The rate of interconversion between the keto and the enol form of acacH is rather slow at room temperature , thus they can be simultaneously detected by NMR spectroscopy it has been observed that the lower the polarity of the solvent, the higher the percentage of the enol tautomer . Electron diffraction studies indicate that in the gas phase acacH adopts the enol configuration with a keto/enol ratio of 8/92. More recently, an X-ray analysis of acacH, carried out at 110 showed that it exists as a mixture of the two enol forms 86 and 87, with the enolic hydrogen atom equally distributed over two positions close to the oxygen atoms as in 88. It should be noted that inclusion compounds containing different host molecules show different ratios of acacH in the enol form. For example, acacH exists as a dynamically averaged 1 1 mixture of 86 and 87 in an inclusion complex with l,T-binaphthyl-2,2 -dicarboxylic acid as host , while l,l-bis( >-hydroxyphenyl)cyclohexane and (4R,5R)-trawi-4,5-bis(hydroxydiphenylmethyl)-2,2-dimethyl-l,3-dioxolane include acacH in pure enolic form. ... 

Rotational isomerization has been described for the phototautomer formed by proton transfer in the excited singlet state of 2,2 -bipyridin-3-ol in hydrocarbon solvents. At room temperature both the primary phototautomer and its rotamer fluoresce, allowing the activation energy for internal rotation to be determined. Excited state tautomerization has also been described for camp-tothecin in acidic aqueous solution and for derivatives of hypericin. Light-induced keto-enol tautomerism has been invoked to explain the fluorescence behaviour of certain benzimidazole compounds. Interconversion of confor-mers of constrained tryptophan derivatives takes place in the first-excited singlet state.The excited state behaviour has been reported for conformationally-distorted porphyrin derivatives. The lifetimes of the S] states of these... 

The excited-state keto-enol tautomeric interconversion has been observed for 1-hy-droxybenzo[h]quinoline 32 in non-polar solvents (cyclohexane, methylcyclohexane, benzene), acetonitrile, and water at ambient temperature (92CPL(193)151, 96JPC17059,... 

Carbonyl (or keto) compounds are interconvertible with their corresponding enols. This rapid interconversion of structural isomers under ordinary conditions is known as tautomerism. Keto-enol tautomerism is catalysed by acids or bases. 

Sugar isomerases catalyze the interconversion between aldose and ketose. Tautomerases catalyze a keto-enol tautomerization. A-Isomerases catalyze the shift of a double bond. The reactions catalyzed by these enzymes proceed through intramolecular oxidation and reduction. 

The structures of most benzophenones have been determined by 1D ( H, l3C, and DEPT) and 2D (COSY, HSQC, HMBC, and NOESY) NMR experiments. The majority of benzophenone NMR spectra have been recorded in CDCI3 and CD3OD. Benzene-c4, mixtures of benzene-<4 and CDCI3 [75], or pyridine-ds have also been used [88,93]. The aforementioned solvents were used to resolve overlapping signals of studied compounds. Deuterated TFA (0.1%) has also been used to increase the rate of keto-enol interconversion in benzophenones. We now turn our attention to the structural elucidation of xanthochymol (138). 

A ketone and an enol differ only in the location of a double bond and a hydrogen. Such isomers are called tautomers ( taw-toe-mers ). The ketone and enol are called keto-enol tautomers. Interconversion of the tautomers is called tautomerization. We will examine the mechanism of this reaction in Chapter 19. For now, the important thing to remember is that the keto and enol tautomers come to equilibrium in solution, and the keto tautomer, because it is usually much more stable than the enol tautomer, predominates at equilibrium. 

---