Equilibria keto-enol

We have seen that protonation of an enolate at oxygen leads to an enol. The enol, an unstable isomer of an aldehyde or ketone, rapidly converts into the carbonyl system It tautomerizes (Section 13-7). These isomers are called enol and keto tautomers. We begin by discussing factors affecting their equilibria, in which the keto form usually predominates. We then describe the mechanism of tautomerism and its chemical consequences. 

An enol equilibrates with its keto form in acidic or basic solution 

Enol-keto tautomerism proceeds by either acid or base catalysis. Base simply removes the proton from the enol oxygen, reversing the initial protonation. Subsequent (and slower) C-protonation furnishes the thermodynamically more stable keto form. 

Both the acid- and base-catalyzed enol-keto interconversions occur rapidly in solntion whenever there are traces of the reqnired catalysts. Remember that although the keto form (usually) predominates, the enol-to-keto conversion is reversible and the mechanisms by which the keto form equilibrates with its enol connterpart are the exact reverse of the preceding two schemes. 

The equilibrium constants for the conversion of the keto into the enol forms, also called enolization, are very small for ordinary aldehydes and ketones, only traces of enol (which is less stable by ca. 8-12 kcal mol ) being present. However, relative to its keto form, the enol of acetaldehyde is about a hundred times more stable than the enol of acetone, because the less substituted aldehyde carbonyl is less stable than the more substituted ketone carbonyl. 

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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. 

Z,Z)-stereoisoiner depends solely on the preponderance of this conformation among the possible conformers, interconvertible by keto-enol equilibria. 

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... 

If the polyelectrolyte can coordinate strongly to a metal ion, marked deceleration effects can be noted, as, for example, in the reactions of Ni + and Co + with pad in the presence of polyphosphates. Modifications of equilibria constants in these micelles must also be recognized as contributing to rate change, e. g., ligand pK or keto-enol equilibria may be altered. 

NUCLEOPHILIC REACTIONS INVOLVING ENOLATE ANIONS Table 10.1 Keto-enoL equiLibria... 

Table XII. Keto-Enol Equilibria or Ethyl Acetoacetate...

Apeloig and coworkers have also studied the effect of silyl substituents on keto-enol equilibria (equation 13)32b,32c. 

It is also possible to examine the effect of oxygen substituents on the stability of arenonium ions. Wirz has studied keto-enol equilibria for phenol,151 naphthol (Wirz J, Personal communication), and anthrol.152,153 The tautomeric constants may be combined with p/y,s for protonation of the keto tautomer and ionization of the phenol to provide pifas f°r protonation of the aromatic ring of phenol and the phenoxide ion. As illustrated in Scheme 18 the unstable keto tautomer of phenol 22 was produced by photolysis of the bicyclooctene dione 21. Except in the case of the anthrone a pA a for protonation of the keto tautomer has not been measured directly. However, values can be estimated from the pfor protonation of the 4,4-dimethylated analog136 with a correction for the substituent effect of the methyl groups. 

In 1978, we observed that flash photolysis of butyrophenone produced acetophenone enol as a transient intermediate, which allowed us to determine the acidity constant KE of the enol from the pH-rate profile (section pH Rate Profiles ) of its decay in aqueous base.4 That work was a sideline of studies aimed at the characterization of biradical intermediates in Norrish Type II reactions and we had no intentions to pursue it any further. Enter Jerry Kresge, who had previously determined the ketonization kinetics of several enols using fast thermal methods for their generation. He immediately realized the potential of the photochemical approach to study keto enol equilibria and quickly convinced us that this technique should be further exploited. We were more than happy to follow suit and to cooperate with this distinguished, inspiring, and enthusing chemist and his cherished wife Yvonne Chiang, who sadly passed away in 2008. Over the years, this collaboration developed into an intimate friendship of our families. This chapter is an account of what has been achieved. Several reviews in this area appeared in the years up to 1998.5 10... 

For the acid-catalyzed ketone -> enol reaction of typical unhydrated ketones, AS appears to be close to the normal or collision theory value for a second-order reaction. For example, AS for the acid-catalyzed bromination of acetone is —12 e.u. (Rice and Kilpatrick, 1923). Since for normal keto-enol equilibria, AS0 is close to zero, the conclusion is that AS for the ketonization reaction would also be close to —12 e.u. 

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). 

S. G. Mills and P. Beak, Solvent effects on keto-enol equilibria tests of quantitative models, J. Org. Chem., 50 (1985) 1216-1224. 

To correlate chemical structure with catalytic activity for these compounds we investigated the keto-enol equilibria with the help of the iron chloride enol test, infrared, and NMR spectra. According to Meyer... 

In contrast to kinetic data, thermodynamic data on enol and enolate formation are far more scarce. This results from the usually very low enol and enolate stabilities which, at equilibrium, make it difficult to measure their proportions relative to the carbonyl compound. This section deals with available data on keto-enol equilibria as well as on acidity constants of the two tautomers. 

Contrary to earlier interpretations of reduction of numerous carbonyl compounds, the role of keto-enol equilibria in electroreductions of carbonyl compounds is rather limited. This is caused by a rapid - acid- or base-catalyzed - conversion of any enol present in the solution or formed in the course of electrolysis into the more... 

Table 1 summarizes these parameters characterizing the keto-enol equilibria, where A refers to the difference between the enol and keto forms. The enol forms are significantly more stable, consistent with the inclusion of an intramolecular hydrogen bond in the structures and concurrent resonance stabilization. The low frequency torsional vibration of the keto forms can account for their significantly greater relative entropy. 

Additional compounds suitable for studies of steric effects on keto-enol equilibria include a-methylacetylacetone (CH3COCHCH3COCH3), diethyhnalonate (CH3CH2OCO-CH2COOCH2CH3), ethyl benzoylacetate (C6H5COCH2COOCH2CH3), and t-butyl acetoacetate (CH3COCH2COOFBU). Some other possible compounds are hsted in Refs. 4 and 5. 

Solvent Effects on Tautomeric Equilibria 4.3.1 Solvent Effects on Keto/Enol Equilibria [36-43,134]... 

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. 

Application of this equation to keto/enol equilibria gives Eq. (4-28), derived by Fowling and Bernstein [57]. 

A wide variety of different theoretical [e.g. Kirkwood function) and empirical cf. Chapter 7) parameters of solvent polarity have successfully been tested using multivariate statistical methods in order to model the solvent-induced changes in keto/enol equilibria [134],... 

Particularly well-studied tautomeric keto/enol equilibria are those of 3-pyridinyl 2-picolyl ketone [138] and t-butyl 2-picolyl ketone [139]. 

Further examples of solvent-dependent keto/enol equilibria can be found in reference [41]. 

Solvent effects similar to those described for the keto/enol equilibria can also be found for other tautomerisms, e.g. lactim/lactam, azo/hydrazone, ring/chain equilibria, etc. [62-64], The pecularities arising here can only be illustrated by means of a few representative examples. 

Ultraviolet spectra have been used for qualitative determinations of the positions of the keto-enol equilibria in phenyl pyrazylmethyl ketone (2-phenacylpyrazine) and the three isomeric pyridinyl pyrazinylmethyl ketones (1470). 

Arylthio)isochromane-l,4-diones 155 (X = S R = Ph, 4-ClC6H4, 4-02NC6H4, etc.) are completely enolized to 155b, while their 5,A-dioxides 155 (X = S02) show the solvent-dependent keto-enol equilibria in which the oxo species are dominating (78CB2859). 

Table 7.4. Keto-enol Equilibria of Ethyl Acetoacetote and Acetylacetone ...

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