Equilibrium constants enolization

The amount of enol present at equilibrium the enol content is quite small for sim pie aldehydes and ketones The equilibrium constants for enolization as shown by the following examples are much less than 1... 

Equilibrium constants and activation parameters have been determined [76ACS(B)101] [for a review see 82AHC(30)127]. Ionization potentials for tautomeric 2-hydroxyselenophenes have been analyzed by comparison with IP data for compounds derived from either tautomeric form. The enol form could not be detected [75ACS(B)647]. 

Other compounds with reactive methylene and methyl groups are completely analogous to the nitroalkanes. Compounds with ketonic carbonyl groups are the most important. Their simplest representatives, formaldehyde and acetone, were considered for many decades to be unreactive with diazonium ions until Allan and Podstata (1960) demonstrated that acetone does react. Its reactivity is much lower, however, than that of 2-nitropropane, as seen from the extremely low enolization equilibrium constant of acetone ( E = 0.9 x 10-7, Guthrie and Cullimore, 1979 Guthrie, 1979) and its low CH acidity (pK = 19.1 0.5, Guthrie et al., 1982). ... 

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

The AS value for pentane-2,4-dione in Table 3 is compatible with a double-minimum potential for the intramolecular hydrogen bond in the enol. This was also the conclusion reached from the microwave and photoelectron spectra. For unsymmetrically substituted diketones, for example 1,1,1-trifluoropentane-2,4-dione, measurement of 13C chemical shifts has been used to estimate values for the equilibrium constant K = [R]/[L] in (38)... 

Traditionally, the position of equilibrium of (15) has been expressed as the percentage of enol, and for neat pentane-2,4-dione this is 79%. The equilibrium constant is especially sensitive to solvents for pentane-2,4-dione the enol content varies from 13% in water to 98% in cyclohexane, corresponding to a ca. 300-fold change in the value of the equilibrium constant. 

Rate and equilibrium constants have been determined for the aldol condensation of a, a ,a -trifluoroacetophenone (34) and acetone, and the subsequent dehydration of the ketol (35) to the cis- and fraw -isomeric enones (36a) and (36b)." Hydration of the acetophenone, and the hydrate acting as an acid, were allowed for. Both steps of the aldol reaction had previously been subjected to Marcus analyses," and a prediction that the rate constant for the aldol addition step would be 10" times faster than that for acetophenone itself is borne out. The isomeric enones are found to equilibrate in base more rapidly than they hydrate back to the ketol, consistent with interconversion via the enolate of the ketol (37), which loses hydroxide faster than it can protonate at carbon. 

Rate and equilibrium constant measurements for the enolization of 3-phenylcoumaran-2-one (82) in aqueous dioxane indicate an enol content of ca 0.1%, a pKg, of 8.9 (6.0 for the enol tautomer), and a fairly symmetrical transition state for enolate anion formation the Brpnsted Pb = 0.52 Below pH 5, enolization is independent of pH, occurring via O-protonation of the enolate. 

Enolization and ketonization kinetics and equilibrium constants have been reported for phenylacetylpyridines (85a), and their enol tautomers (85b), together with estimates of the stability of a third type of tautomer, the zwitterion (85c). The latter provides a nitrogen protonation route for the keto-enol tautomerization. The two alternative acid-catalysed routes for enolization, i.e. O- versus Af-protonation, are assessed in terms of pK differences, and of equilibrium proton-activating factors which measure the C-H acidifying effects of the binding of a proton catalyst at oxygen or at nitrogen. 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

To indicate the importance of enolization, equilibrium constants for a number of substrates are shown in Table 10.1. These equilibrium constants are only approximate, and they do depend very much on the solvents employed. Nevertheless, we can see that the equilibrium constant K = [enol]/[keto] is very small for substrates like acetaldehyde, acetone, and cyclohexanone, with only a few molecules in every million existing in the enol form. However, in ethyl acetoac-etate, enol concentrations are measured in percentages, and in acetylacetone the equilibrium constant indicates the enol form can be distinctly favoured over the normal keto form. In hexane solution, only 8% of acetylacetone molecules remain in the keto form. 

Spectral evidence" indicates an equilibrium between tetrahedral and octahedral Co" in iViV-dimethylacetamide and the equilibrium constant for [Co (tet)]/[Co (oct)] is reported at various temperatures. The complexes of acetylhydrazine (A), [CoA3]X2 (X = Cl or Br) and [Co(NCS)2A2]H20 and the tri-N-deuterio-analogue[Co(NCS)2(Ad3)2]D20 have been isolated and examined by i.r. Cationic complexes of JV-acyl hydrazines have been isolated with ligands in their keto-form, RCO-NH-NH2 however, the ligands also react in their enol form, RC(OH) = NNH2, forming neutral complexes (R = Me, Pr", Pr , or Ph). ... 

Streitwieser and coworkers recently reported that the lithium enolate of p-(phenylsul-fonyl)isobutyrophenone exists as a monomer-dimer mixture iu THE, with the equilibrium constant = (5.0 0.1) x 10 M . The rate of the reaction of the enolate with p-tert-butylbenzyl bromide was measured spectrophotometricaUy at the enolate concentration range of 7 x 10 to 5 x 10 M, where the percentage of the monomer was 4.5 to 11%. The logarithmic plot of the rate vs the enolate concentration was linear with a slope of 0.50 0.04, indicating that the reacting species is the monomer that exists as a minor component in the equilibrium with the dimer. 

Jnmps of a proton along the hydrogen bond represent another type of dynamics observed in hydrogen-bonded complexes. Mechanistically, this process is simplest for intramolecular hydrogen bonds. The fast enol-enolic equilibrium shown in Scheme 2.2 illustrates an intramolecular proton-jumping system [27]. Here, substituent X dictates the equilibrium constant as well as the rate of proton transfer. It should be noted that such proton jumps can be stopped on the H NMR time scale only at very low temperatures. 

Nucleophilic Additions to Alkenes. Nucleophilic additions to alkenes (Scheme 3.9) are mechanistically very closely related to an ElcB process. In fact, the addition process simply involves a reversal of the steps in response to an equilibrium constant that favors the addition product over the alkene. A notable example is the Michael addition of an enolate to an alkene bearing a strong electron-withdrawing group (EWG). 

The equilibrium constant for a tautomeric interconversion is simply the ratio of the mole fractions of the two forms for example, the ratio of enol to oxo forms of acetone12 in water at 25°C is 6.0 x 10 9, while that for isobutyraldehyde is 1.3 x ICE4. The ratio of 2-hydroxypyridine to 2-pyridone is about 10 3 in water but increases to 0.6 in a hydrocarbon solvent and to 2.5 in the vapor phase.13 14 The ratio of dipolar ion to uncharged pyridoxine (Eq. 2-5) is 4 at 25°C in water.15 The ratios of tautomers B, C, and D to the tautomer A of uracil (Eq. 2-4) are small, but it is difficult to measure them quantitatively.16 These tautomeric ratios are defined for given overall states of protonation (see Eq. 6-82). The constants are independent of pH but will change if the overall state of protonation of the molecule is changed. They may also be altered by... 

The addition of an enolate anion to C02 to form a (3-oxoacid represents one of the commonest means of incorporation of C02 into organic compounds. The reverse reaction of decarboxylation is a major mechanism of biochemical formation of C02. The equilibrium constants usually favor decarboxylation but the cleavage of ATP can be coupled to drive carboxylation when it is needed, e.g., in photosynthesis. 

Table 8.6 Approximate Values of Keto-Enol Equilibrium Constants...

It is now common experimental practice to react ketones with lithium diisopropyl amide (LDA) in order to generate the enolate of the ketone. This methodology has largely replaced the older approach to enolates, which employed alkoxide bases to remove a proton alpha to the carbonyl group. Comparison of the equilibrium constants for these two acid-base reactions reveals why the LDA method is preferable. The use of the amide base leads to essentially complete conversion of die ketone to its enolate (Keq 1016). At equilibrium, there is virtually no... 

Keto-enol equilibrium constants for simple /i-dicarbonyl compounds, RCOCH2COX (R = X = Me R = Me, Ph for X = OEt) have been measured in water1423 by a micelle perturbation method previously reported for benzoylacetone142b (R = Ph, X = Me). The results have been combined with kinetic data for nitrosation by NO+, C1NO, BrNO, and SCNNO in all cases, reaction with the enol was found to be rate limiting. 

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). 

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