4468-52-4Relevant academic research and scientific papers
Generation and stability of a simple thiol ester enolate in aqueous solution
Amyes, Tina L.,Richard, John P.
, p. 10297 - 10302 (1992)
The exchange for deuterium of the α-protons of ethyl thioacetate and of acetone in 3-quinuclidinone buffers in D2O at 25 °C and pD = 7.7-9.3 was followed by 1H NMR spectroscopy. The exchange reactions lead to the appearance of signals due to the α-CH2D and α-CHD2 species that are cleanly resolved from each other and from the signal due to the α-CH3 species. Observed rate constants for the 3-quinuclidinone-catalyzed exchange were determined during exchange of 30-37% of the first α-proton of each methyl group of ethyl thioacetate or acetone. The rate constants for exchange correspond to those for deprotonation of ethyl thioacetate and acetone by 3-quinuclidinone to give the free enolates, with kB = 2.2 × 10-5 and 5.2 × 10-4 M-1 s-1, respectively. These rate constants were combined with the known pKa of acetone to estimate pKa = 20.4-21.5 for ethyl thioacetate and kBH = 1.7 × 108 to 2 × 109 M-1 s-1 for the reaction of the free thiol ester enolate with the 3-quinuclidinone cation. The lifetime of the buffer acid-enolate intimate ion pair BH+·-CH2COSEt with respect to proton transfer to give B-CH3COSEt is estimated to be from 10-9 to 10-10 s. These results provide evidence against the suggestion that enzyme-catalyzed Claisen condensation and related reactions proceed by concerted mechanisms that are enforced by the insignificant lifetime of the thiol ester enolate in the presence of an acidic amino acid residue at the enzyme.
Determination of the p K a of Cyclobutanone: Bronsted correlation of the general base-catalyzed enolization in aqueous solution and the effect of ring strain
Cope, Steven M.,Tailor, Dishant,Nagorski, Richard W.
, p. 380 - 390 (2011)
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 D2O 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 Bronsted 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 (kBH = 5 × 108 -2 × 109 M-1 s-1). Combining the rate constants for deprotonation of cyclobutanone (kB) and protonation of the enolate of cyclobutanone (kBH) by 3-quinuclidinone and its conjugate acid, the pKa of the α-protons of cyclobutanone has been estimated to be pKa = 19.7-20.2.
A Comparison of the Electrophilic Reactivities of Zn2+ and Acetic Acid as Catalysts of Enolization: Imperatives for Enzymatic Catalysis of Proton Transfer at Carbon
Crugeiras, Juan,Richard, John P.
, p. 5164 - 5173 (2004)
The deprotonation of the α-CH3 and α-CH 2OD groups of hydroxyacetone and the α-CH3 groups of acetone in the presence of acetate buffer and zinc chloride in D 2O at 25 °C was followed by monitoring the incorporation of deuterium by 1H NMR spectroscopy, and the rate laws for catalysis of these reactions by acetate anion and zinc dication were evaluated. Relative to solvent water at a common standard state of 1 M, Zn2+ provides 6.3 and 4.4 kcal/mol stabilizations, respectively, of the transition states for deprotonation of the α-CH2OD and α-CH3 groups of hydroxyacetone by acetate anion, and a smaller 3.3 kcal/mol stabilization of the transition state for deprotonation of the α-CH3 group of acetone. There is only a 1.4 kcal/mol smaller stabilization of the transition state for the acetate-ion-promoted deprotonation of acetone by the Bronsted acid acetic acid than by Zn2+, which shows that, in the absence of a chelate effect, there is no large advantage to the use of a metal dication rather than a Bronsted acid to stabilize the transition state for deprotonation of α-carbonyl carbon.
The influence of H/D kinetic isotope effect on radiation-induced transformations of hydroxyl-containing compounds in aqueous solutions
Bekish, Andrei V.,Nepachalovich, Palina S.,Shadyro, Oleg I.,Shmanai, Vadim V.
, p. 732 - 744 (2020/12/28)
Vicinal diols and its derivatives can be exploited as model compounds for the investigation of radiation-induced free-radical transformations of hydroxyl-containing biomolecules such as carbohydrates, phospholipids, ribonucleotides, amino acids, and peptides. In this paper, for the first time, the prospects of isotope reinforcement approach in inhibiting free-radical transformations of hydroxyl-containing compounds in aqueous solutions are investigated on the example of radiolysis of 1,2-propanediol and 1,2-propanediol-2-d1 aqueous solutions. At an absorbed dose rate of 0.110 ± 0.003 Gy·s?1 a profound kinetic isotope effect (KIE) is observed for the non-branched chain formation of acetone, which is a final dehydration product of predominant carbon-centred radicals CH3·C(OH)CH2OH. In 0.1 and 1 M deaerated solutions at pH 7.00 ± 0.01, the values of KIE are 8.9 ± 1.7 and 15.3 ± 3.1, respectively. A rationale for the fact that a strong KIE takes place only in the case of chain processes, which may occur during free-radical transformations of vicinal diols, is also provided herein based on the results of 2-propanol and 2-propanol-2-d1 indirect radiolysis. Lastly, the lack of KIE is shown in the case of 2-butanone formation from 2,3-butanediol or 2,3-butanediol-2,3-d2. This indicates that the type (primary, secondary) of the β-carbonyl radicals formed as a result of CH3·C(OH)CH(OH)R (R = H, CH3) dehydration determines the manifestation of the effect.
Highly efficient antibody-catalyzed deuteration of carbonyl compounds
Shulman, Avidor,Sitry, Danielle,Shulman, Hagit,Keinan, Ehud
, p. 229 - 239 (2007/10/03)
Antibody 38C2 efficiently catalyzes deuterium-exchange reactions at the α position of a variety of ketones and aldehydes, including substrates that have a variety of sensitive functional groups. In addition to the regio- and chemoselectivity of these reactions, the catalytic rates (kcat) and rate-enhancement values (kcat/kun) are among the highest values ever observed with catalytic antibodies. Comparison of the substrate range of the catalytic antibody with highly evolved aldolase enzymes, such as rabbit-muscle aldolase, highlights the much broader practical scope of the antibody, which accepts a wide range of substrates. The hydrogen-exchange reaction was used for calibration and mapping of the antibody active site. Isotope-exchange experiments with cycloheptanone reveal that the formation of the Schiff base species (as concluded from the 16O/18O exchange rate at the carbonyl oxygen) is much faster than the formation of the enamine intermediate (as concluded from the H/D exchange rate), and both steps are faster than the antibody-catalyzed aldol addition reaction.
Combined Deuterium Nuclear Magnetic Resonance and Mass-spectrometric Studies of the Exchange Reactions of Ketones over Supported Metal Catalysts
Pope, Christopher,Kemball, Charles,McDougall, Gordon S.
, p. 747 - 752 (2007/10/02)
Deuterium NMR spectroscopy has been used in conjunction with mass spectrometry to study the exchange reaction of the ketones acetone, butan-2-one and cyclopentanone over a variety of supported metal catalysts.In many of the experiments simple, random, stepwise exchange was prevalent.However, in certain instances multiple exchange occurred.For butan-2-one and cyclopentanone this multiple exchange was essentially limited to the protons on carbon atoms adjacent ot the carbonyl group, while for acetone a strong preference towards exchange into only a single methyl groupwas noted.Some hydrogenation to propan-2-ol accompanied the multiple exchange of acetone, with the majority of the alcohol being formed by addition of D2 across the carbon oxygen double bond without simultaneous exchange into the methyl group, suggesting independent η1 and η2 adsorbed acetone surface intermediates for the exchange and hydrogenation reactions respectively.
Reaction of the anionic acylmethylidyne cluster [Ru3(CO)9(μ3-CO)(μ 3-CC(O)CH3)]- with CO and H2: Reversible C-C and C-H bond forming reactions
Sailor, Michael J.,Sabat, Michal,Shriver, Duward F.
, p. 728 - 736 (2008/10/08)
The result of reaction of the acylmethylidyne cluster [Ru3(CO)9(μ3-CO)(μ 3-CC(O)CH3)]- (1) with either CO or H2 is a cluster with an O→Ru bond between a metal vertex and the C-C(O)CH3 moiety. In the reaction with CO a carbon-carbon bond is formed, producing the μ2-η2-acyl cluster [Ru3(CO)7(μ-CO)3-(μ 2-η2-CH3C(O)CCO)]- (2). Similarly a carbon-hydrogen bond is formed on treatment of 1 with H2, generating the μ3-η2-acyl cluster [HRu3(CO)9(μ3-η 2-CHC(O)CH3)]- (3). The reaction of 1 with CO is rapid and reversible, with an equilibrium constant at 20°C of 2.1 (3) atm-1 (for 1 + CO ? 2). The acylketenylidene cluster [Ru3(CO)7(μ-CO)3(μ2-η 2-CH3C(O)CCO)]- (2) has been characterized in situ by variable-temperature and two-dimensional 13C NMR spectroscopy. Isotopic tracer studies indicate the ketenyl CO of 2 originates from a cluster carbonyl on 1. Protonation of 3 occurs at ruthenium to generate H2Ru3(CO)9(μ3-η 2-CHC-(O)CH3) (4). The O→Ru interaction in compounds 2-4 can be readily disrupted. For example, the CO adduct [Ru3(CO)7(μ-CO)3(μ2-η 2-CH3C(O)CCO)]- (2) reverts to [Ru3(CO)9(μ3-CO)(μ 3-CC(O)CH3)]- (1) on removal of CO, and the acetyl oxygen of [HRu3(CO)9(μ3-η 2-CHC(O)CH3)]- (3) can be alkylated by CH3SO3CF3 to give the previously characterized vinylidene cluster H2Ru3(CO)9(μ3-η 2-C=C(OCH3)CH3) (5). Treatment of 3 with DCl produces 4-d1, which rapidly eliminates acetone-d1. The benzyltrimethylammonium salt of 1 crystallizes in the orthorhombic space group P212121 (No. 19) with a = 13.978 (5), b = 21.431 (7), and c = 9.224 (4) A?, V = 2763 (3) A?3, and D(calcd) = 1.90 g cm-3 for mol wt 788.6 and Z = 4. Final discrepancy indices are RF = 5.4% and RwF = 7.4% for 1219 independent reflections with I > 3σ(I).
The Effect of Surface Hydroxyl Groups upon the Deactivation of Excited Triplet Acetone Adsorbed on Porous Vycor Glass
ANPO, Masakazu
, p. 1221 - 1224 (2007/10/02)
H-D exchange between deuterated surface hydroxyl groups and excited triplet acetone has been observed on porous Vycor glass, proceeding via surface hydroxyl group-assited photoenolization of acetone.This chemical process evidences that surface hydroxyl groups play a significant role in determining the fate of the excited triplet acetone adsorbed on Vycor glass by a strong hydrogen bonding.
