Rate Constants For Enolization Research Articles

Determination of the pKaof Cyclobutanone: Brønsted Correlation of the General Base-Catalyzed Enolization in Aqueous Solution and the Effect of Ring Strain

The induction of strain in carbocycles, thereby increasing the amount of s-character in the C-H bonds and the acidity of these protons, has been probed with regard to its effect on the rate constants for the enolization of cyclobutanone. The second-order rate constants for the general base-catalyzed enolization of cyclobutanone have been determined for a series of 3-substituted quinuclidine buffers in D(2)O at 25 °C, I = 1.0 M (KCl). The rate constants for enolization were determined by following the extent of deuterium incorporation (up to ∼30% of the first α-proton) into the α-position, as a function of time. The observed pseudo-first-order rate constants correlated to the [basic form] of the buffer and yielded the second-order rate constants for the general base-catalyzed enolization of cyclobutanone for four tertiary amine buffers. A Brønsted β-value of 0.59 was determined from the second-order rate constants determined. Comparison of the results for cyclobutanone to those previously reported for acetone and a 1-phenylacetone derivative, under similar conditions, indicated that the ring strain of the carbocycle appeared to have only a small effect on the general base-catalyzed rate constants for enolization. The similarity of the rate constants for the general base-catalyzed enolization of cyclobutanone to those determined for acetone allowed for an estimation of the limits of the rate constant for protonation of the enolate intermediate of cyclobutanone by the conjugate acid of 3-quinuclidinone (k(BH) = 5 × 10(8) - 2 × 10(9) M(-1) s(-1)). Combining the rate constants for deprotonation of cyclobutanone (k(B)) and protonation of the enolate of cyclobutanone (k(BH)) by 3-quinuclidinone and its conjugate acid, the pK(a) of the α-protons of cyclobutanone has been estimated to be pK(a) = 19.7-20.2.

Binding Catalysis and Inhibition by Metal Ions and Protons in the Enolization of Phenylacetylpyrazine

A study of the enolization of phenylacetylpyrazine (PzCOCH(2)Ph) catalyzed by acid, base and metal ions in aqueous solution shows, unusually, that metal ions are more effective catalysts than protons, e.g., for zinc k(Zn)/k(H) = 600. Such behavior contrasts with that of the structurally related phenacylpyridine (PyCH(2)COPh) for which k(Zn)/k(H) = 0.0065. To interpret this difference, equilibrium constants for the tautomerization of phenylacetylpyrazine and for binding of protons and metal ions to its keto tautomer and enolate anion have been measured or estimated and are compared with existing measurements for phenacylpyridine. A tautomeric constant, K(E) = 1.2 x 10(-3) (pK(E) = 2.9), is derived by combining forward and reverse rate constants for enolization measured, respectively, by iodination or bromination of the keto tautomer and relaxation of the less stable enol. For the keto tautomer, NMR measurements yield a pK(a) = -0.90 for N-protonation, and spectrophotometric measurements give pK(a) = 11.90 for ionization to an enolate anion. For the enol, pK(a) values of 0.44 and -4.80 for mono- and diprotonation are obtained from the pH profile for ketonization and absorbance measurements for the transient enol reactant. Binding constants for metal ions (Cu(2+), Ni(2+), Zn(2+), Co(2+), and Cd(2+)) are derived from the saturation of their catalysis of the ketonization reaction. It is found that ketonization is efficiently catalyzed by metal ions but inhibited by acid. These findings, and the striking difference from phenacylpyridine, are ascribed to differences in thermodynamic driving force arising from stronger binding of the proton to the more basic pyridine than pyrazine nitrogen atom in both the reactant keto tautomer and in the enaminone or zwitterion product of the rate-determining (proton transfer) step of the enolization.

Ab initio analysis on metal ion catalysis in the enolization reactions of some acetylheterocycles: kinetics of the enolization reactions of 3‐acetyl‐5‐methylisoxazole, 5‐acetyl‐3‐methylisoxazole and 3(5)‐acetylpyrazole

AbstractKinetic data on the enolization reaction of 3‐acetyl‐5‐methylisoxazole, 5‐acetyl‐3‐methylisoxazole, 3(5)‐acetylpyrazole and some previously studied acetylheterocycles have been the object of a comprehensive ab initio analysis. Enolization rate constants were measured spectrophotometrically by the halogen trapping technique at 25 °C and ionic strength of 0.3 mol dm−3 in water, in acetate buffers, in dilute hydrochloric acid, in dilute sodium hydroxide and in the presence of some metal ion salts. In the spontaneous (water) and base (acetate) catalysed reactions the ketones investigated are generally more reactive than acetophenone, according to the electron‐withdrawing effect of the heterocyclic ring compared with the benzene ring. In particular, acetylisoxazoles, 3(5)‐acetylpyrazole and acetylthiazoles are more reactive than acetylfurans, 2‐acetylpyrrole and acetylthiophenes respectively, and this can be attributed to the additional effect of the second heteroatom in the heterocyclic moiety. On the other hand, the compounds investigated are generally less reactive than acetophenone in the H3O+‐catalysed reaction. Ab initio calculations on the relative stability of the protonated and unprotonated forms of the substrates investigated have been compared with the kinetic results obtained in acid solutions. As far as the metal ion catalysis is concerned, an approach in terms of ΔΔE can give an estimate of the combined contributions of charge densities and frontier orbitals to the interaction of the substrate with the metal ion catalyst. A comparison of experimental metal activating factor values and ab initio calculations outlines the importance of charge density on the carbonyl oxygen atom of acetylheterocycles with one heteroatom. An analogous comparison for acetylheterocycles with two heteroatoms suggests the formation of a chelate complex or transition state, in which the metal ion coordinates both the carbonyl oxygen and the aza nitrogen, whenever these two atoms are suitably placed within the molecular structure of the acetylheterocycle. Copyright © 2002 John Wiley & Sons, Ltd.

The reversible enolization and hydration of pyruvate: possible roles of keto, enol, and hydrated pyruvate in lactate dehydrogenase catalysis

The reversible enolization and hydration of pyruvic acid and pyruvate anion were monitored using spectrophotometric methods at several temperatures. Widely varying values for the equilibrium constant for the enolization of pyruvic acid and pyruvate ion appear in the literature. To accurately determine the position of equilibrium for the enolization reaction, we have developed a method that gives consistent results in which purified samples of sodium pyruvate are first "titrated" with triiodide ion to remove any triiodide-scavenging impurities such as those resulting from aldol condensation reactions. After reequilibration to allow the regeneration of enol pyruvate, the addition of small quantities of triiodide result in an initial burst in the decrease of absorbance at 353 nm, followed by the much slower zero-order decrease due to the formation of new enol pyvuvate molecules. The absorbance change during the burst phase of the reaction is proportional to the enol concentration plus that of any triiodide-scavenging impurity which may be present in the original pyruvate solution. Thus, as the quantity of triiodide used in the pretreatment stage of the experiments is increased, these burst absorbance changes, ΔA, decrease until a constant value of ΔA is reached. Accordingly, this final ΔA value is proportional to enol pyruvate (or enol pyruvic acid) in the absence of triiodide-scavenging impurity, allowing the accurate and reproducible determinations of Kenol. The equilibrium constants for both pyruvate and pyruvic acid are relatively temperature insensitive and, typically, Kenol (pyruvate anion) = 2.6 × 10-5 and Kenol (pyruvic acid) = 7.8 × 10-5 at 25.0°C. The zero-order phase of the reaction of triiodide ion may be used to calculate rate constants for enolization. The hydration and dehydration of pyruvic acid were followed directly by following absorbance changes in the peak at 340 nm due to the keto group. The thermodynamic and kinetic results reported in this paper are used to help determine whether the observed "substrate" inhibition of the lactate dehydrogenase catalyzed reduction of pyruvate is actually caused by keto, hydrated, or enol pyruvate.Key words: pyruvate, enolization, hydration, lactate dehydrogenase.

Kinetics and Mechanism of the Formation and Acid Dissociation of Cobalt(II), Nickel(II), and Copper(II) Complexes with the Highly Enolized beta-Diketone 3-(N-Acetylamido)pentane-2,4-dione (=Hamac) in Aqueous Solution.

The beta-diketone Hamac = 3-(N-acetylamido)pentane-2,4-dione was characterized by potentiometric, spectrophotometric, and kinetic methods. In water, Hamac is very soluble (2.45 M) and strongly enolized, with [enol]/[ketone] = 2.4 +/- 0.1. The pK(a) of Hamac is 7.01 +/- 0.07, and the rate constants for enolization, k(e), and ketonization, k(k), at 298 K are 0.0172 +/- 0.0004 s(-1) and 0.0074 +/- 0.0015 s(-1), respectively. An X-ray structure analysis of the copper(II) complex Cu(amac)(2).toluene (=C(21)H(28)CuN(2)O(6); monoclinic, C2/c; a = 20.434(6), b = 11.674(4), c = 19.278(6) Å; beta = 100.75(1) degrees; Z = 8; R(w) = 0.0596) was carried out. The bidentate anions amac(-) coordinate the copper via the two diketo oxygen atoms to form a slightly distorted planar CuO(4) coordination core. Rapid-scan stopped-flow spectrophotometry was used to study the kinetics of the reaction of divalent metal ions M(2+) (M = Ni,Co,Cu) with Hamac in buffered aqueous solution at variable pH and I = 0.5 M (NaClO(4)) under pseudo-first-order conditions ([M(2+)](0) >> [Hamac](0)) to form the mono complex M(amac)(+). For all three metals the reaction is biphasic. The absorbance/time data can be fitted to the sum of two exponentials, which leads to first-order rate constants k(f) (fast initial step) and k(s) (slower second step). The temperature dependence of k(f) and k(s) was measured. It follows from the kinetic data that (i) the keto tautomer of Hamac, HK, does not react with the metal ions M(2+), (ii) the rate constant k(f) increases linearly with [M(2+)](0) according to k(f) = k(0) + k(2)[M(2+)](0), and (iii) the rate constant k(s) does not depend on [M(2+)](0) and describes the enolization of the unreactive keto tautomer HK. The pH dependence of the second-order rate constant k(2) reveals that both the enol tautomer of Hamac, HE, and the enolate, E(-), react with M(2+) in a second-order reaction to form the species M(amac)(+). At 298 K rate constants k(HE) are 18 +/- 6 (Ni), 180 +/- 350 (Co), and (9 +/- 5) x 10(4) (Cu) M(-1) s(-1) and rate constants k(E) are 924 +/- 6 (Ni), (7.4 +/- 0.6) x 10(4) (Co), and (8.4 +/- 0.2) x 10(8) (Cu) M(-1) s(-1). The acid dissociation of the species M(amac)(+) is triphasic. Very rapid protonation (first step) leads to M(Hamac)(2+), which is followed by dissociation of M(Hamac)(2+) and M(amac)(+), respectively (second step). The liberated enol Hamac ketonizes (third step). The mechanistic implications of the metal dependence of rate constants k(HE), k(E), k(-HE), and k(-E) are discussed.

Structural effects on the rates of formation and the stability of enols of cyclic benzyl ketones

The acid dissociation constants (KaK), the keto-enol equilibrium constants (K& and the rate constants for enolization of the cyclic benzyl ketones 2-indanone (la), 2-tetralone (3,4-dihydro-2( 1H)-naphthalenone, lb) and 2-benzosuberone (3,4- benzo-3-cyclohepten-I-one, IC) were measured in aqueous solution at 25 C. The rate constants for ketonization of the enols and the acid dissociation constants (KaE) for the corresponding enols were also determined. The presence of a conjugating phcnyl group provides sufficient stabilization of the negative charge to enable these ketones to ionize in the pH range. pKaK valucs wcrc determined from the rate constants for ionization of the ketones and for ketonization of the enolate ions. These valucs were confirmed by spectral titration. The acidity of the ketones decreases with increasing size; pKaK values are 12.2 (la), 12.9 (lb), and 14.9 (IC). Similarly, the acid dissociation constants of the enols decrease with increasing ring size; pKaE's are 8.3 (Za), 9.2 (2b), and 10.0 (2c). Equilibrium constants for enolization also vary with ring size; pKE values are 3.8 (la), 3.6 (lb), and 4.9 (IC).

Estimation of malonic acid and methylmalonic acid enolization rate constants by an isotopic-exchange reaction using proton NMR spectroscopy

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEstimation of malonic acid and methylmalonic acid enolization rate constants by an isotopic-exchange reaction using proton NMR spectroscopyEddy W. Hansen and Peter RuoffCite this: J. Phys. Chem. 1988, 92, 9, 2641–2645Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://doi.org/10.1021/j100320a048RIGHTS & PERMISSIONSArticle Views267Altmetric-Citations21LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (556 KB) Get e-Alerts

The Solvent Effects of Water–Dimethyl Sulfoxide Mixtures on the Keto-Enol Tautomerization Rate of Di-n-alkyl β-Diketones

Abstract The kinetic solvent effects of water–dimethyl sulfoxide (DMSO) mixtures on the ketonization and the enolization rate constants of eight di-n-alkyl β-diketones were analyzed in terms of the group-transfer free energy from water to the mixed solvents. The transfer free energy of the transition state, as calculated from the rate constant and the partition coefficient of the keto or enol form, is found to be divided into three contributions: the two group-transfer free energies of the “transition state skeleton” and the methylene group, and the transfer free energy change due to the inductive effect of the n-alkyl group.

The excess acidity method. The basicities, and rates and mechanisms of enolization, of some acetophenones and acetone, in moderately concentrated sulfuric acid

The X-function method has been used to evaluate the basicities of six nuclear-substituted acetophenones and acetone, using a combination of new measurements and literature data; the protonation [Formula: see text] of acetone was found to be −5.37. The same method, which involves the excess medium acidity, when used to analyze the enolization rate constants obtained from the measured bromination rates, shows that most of the acetophenones enolize by an A-2 process involving two water molecules in the rate-determining step. Observed linear free energy relationships for the basicities and the enolization rates imply a relatively early transition state for the enolization. Acetone was found to enolize by a similar mechanism in sulfuric acid solutions more dilute than 81% w/w, but at higher acidities bisulfate ion was the preferred base. The mechanistic behaviour of 4-nitroacetophenone was found to be different, not A-2 but either A-1 or A-SE2.

The enol content of simple carbonyl compounds: a kinetic approach

Following a suggestion of Lienhard and Wang, we demonstrate that the enol content of simple carbonyl compounds can be estimated as the ratio of the rate constants for acid-catalyzed enolization of the carbonyl compound and acid-catalyzed hydrolysis of the corresponding methyl enol ether. Values so estimated are in excellent agreement with those determined by our thermochemical method. Sufficient data are available for the following; compound, pKEnol: acetaldehyde, 4.7; propionaldehyde, 4.2; isobutyraldehyde, 2.7; acetone, 7.0; cyclopentanone, 6.7; cyclohexanone, 5.3; cycloheptanone, 7.2; cyclooctanone, 6.6; p-nitroacetophenone, 4.9; p-bromoacetophenone, 6.2; acetophenone, 6.6; p-methylacetophenone, 7.0; p-methoxyacetophenone, 7.3; and by estimating the rate constants for enolization, the following; indanone, 7; 2-phenyl-2-propanone, 4; cyclopropyl methyl ketone, 8; chloroacetaldehyde, 2 (corrected for hydration); phenylacetaldehyde, 2.

Bromination of saturated aliphatic ketones in an acidic medium: effects of structure on apparent rate constants for enolization and for bromination of the enol

Bromination of saturated aliphatic ketones in an acidic medium: effects of structure on apparent rate constants for enolization and for bromination of the enol