Enol constant

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 rates of ketonization are usually easier to determine (by flash photolysis) than the much slower rates of enolization that require laborious conventional methods such as measuring bromination kinetics and analysis of the reaction products. Thus the shape of the profile is conveniently explored by flash photolysis over a wide range of pH for kK, and only a single point on the lower curve is then required to determine the enolization constant Ke-... 

Let us have a look at some instructive pH-rate profiles. That for acetophenone was already discussed in the section pH-Rate Profiles (Fig. 3). Its general shape is characteristic for the behavior of the enols of simple ketones and aldehydes. The enolization constants of aldehydes tend to be higher than those of ketones compare, for example, pA h(acetonc) = 8.33 and pA"E(acetaldehyde) 6.23. This is in line with the well-known stabilizing effect of alkyl substitution on double bonds, in particular of the polar C=0 bond, a-Substitution of ketones and aldehydes by alkyl or, better still, by aryl groups further stabilizes the enol, so that the enol content of 2,2-diphenylacetaldehyde reaches 10%.34... 

The enolization constants of carboxylic acids to form enediols are generally still lower than those of ketones. The pAE of acetic acid is about 20.35 Due to the relatively high acidity of 1,1-enediols, the enol content of carboxylate anions is somewhat higher. When the carboxylate is attached to cyclopenta-dienyl, a strong mesomeric electron acceptor, the conjugate acid of the enol, fulvene-l,l-diol, becomes a strong acid, pAa = 1.3, and the pAE of the enol anion is reduced to 5.0 (Almstead JIK and Wirz J, Unpublished data).36,37... 

Aromatic enols, that is, phenols, are generally more stable than their ketone tautomers. The pH-rate profile for the enolization reaction of 2,4-cyclohexadienone to parent phenol is shown in Fig. V.44 The rate constant kK of the reverse reaction was determined at pH = 1 by measuring the rate of isotopic exchange and correcting for isotope effects to determine the enolization constant Kb = = 5.4 x 1012, pA E = -12.73. The dashed line in... 

E is the so-called enol constant and measures the enolization capability of the diketo form ( = 1 for ethyl acetoacetate by definition). Thus, the so-called desmotropic constant L is a measure of the enoHzation power of the solvent. By definition, the values of L are equal to the equilibrium constants of ethyl acetoacetate E = 1), determined in different solvents [24]. This desmotropic constant seems to be the first empirical solvent parameter. It describes the relative solvation power of a solvent for diketo and enol forms of 1,3-dicarbonyl compounds. It was measured only for a few solvents and was soon forgotten. 

Flash photolysis has contributed much to our understanding of enol chemistry in aqueous solution. The equilibrium constant for the enolization of simple ketones, = C enoi/c ketonc is usually too small permit a direct determination of enol concentrations cenoi at equilibrium. For example, the enolization constant of acetone is pk) 8.3 the relative amount of 2-hydroxypropene is thus only 5 ppb in aqueous solution. Nevertheless, most reactions of carbonyl compounds proceed via enol intermediates, which, once... 

Rate constants for the reverse tautomerization reaction can be measured by thermal halogenation of ketones or isotope exchange reactions. Combination of the rate constants of ketonization, A , and enolization, kK, provides accurate equilibrium constants of enolization, K k> /kK. The acidity constants of ketones, K, and of the corresponding enols, Kf, are related to the enolization constant Kti by a thermodynamic cycle, pl E = pKf—pK (Scheme 5.21). 

The rate-determining step always corresponds to protonation or deprotonation of a carbon atom, while equilibration of oxygen acids with their conjugate bases is established rapidly. This fact can be used to determine the acidity constants of enols, ynols and ynamines by flash photolysis, Kf, either kinetically, from downward bends in the pH rate profiles indicating a pre-equilibrium, or from the changes of the transient absorption in solutions of different pH (spectrographic titration). Such studies have provided some remarkable benchmark numbers, such as the acidity constant of phenylynol (pKf < 2.1),476 phenylynamine (pKf < 18.0)477 and its pentafluoro derivative (pKf = 10.3),478 and of the carbon acid 2,4-cyclohexadienone, pKf = —2.9 475 The enolization constant of 2,4-cyclohexadienone is pKE = 12.7. 

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). 

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... 

The keto-carbonyl C signal at 5c = 200.9 would only fit the aflatoxins B, and M,. In the C NMR spectrum an enol ether-C// fragment can also be recognised from the chemical shift value of 5c = 145.8 and the typical one-bond coupling constant Jch = 196 Hz the proton involved appears at Sh = 72, as the CH COSY plot shows. The H triplet which belongs to it overlaps with a sing-... 

Figure 4.10 is plot of the Bronsted relationship for hydrolysis of an enol ether. The plot shows that the effectiveness of the various carboxylic acids as catalysts is related to their dissociation constants. In this particular case, the constant a is 0.79 ... 

Table 7.12. Equilibriuib Constants for Enolization of Some Carbonyl Compounds...

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]. 

Two isomeric structures can be obtained for these products ( -113 and/or Z-113). The stereochemistry was conveniently elucidated on the basis of NMR data which showed coupling constant values 7(H,CO) consistent with the -isomers only. The formation of 113 was explained to occur via the enolate salts (86JHC199). Catalytic... 

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. 

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