Rates Of Enolization Research Articles

Lewis acidity and substituent effects influence aldehyde enolization and C–C coupling in beta zeolites

The Claisen-Schmidt condensation between propanal and benzaldehyde was used a model aldol reaction to assess the reactivity of tetravalent framework Lewis acid sites (Ti, Zr, Sn, Hf) in hydrophobic beta zeolites (M-*BEA) and determine rates of enolization and carbon–carbon (C–C) bond formation along with selectivities among cross- and self-condensation products. Rates of enolate formation during liquid phase reactions (393 K) span nearly 100-fold, depending on the identity of the metal heteroatom, and correlate with enthalpies for adsorption of pyridine in liquid-filled pores of M-*BEA, as measured by isothermal titration calorimetry. Comparisons among adsorption enthalpies suggest that tetrahedrally substituted Zr and Hf are more effective Lewis acids than Sn and Ti for coordinating aldehydes within these environments. Ratios of initial rates of C–C coupling between propanal and benzaldehyde compared to propanal self-condensation were less than unity for all M-*BEA catalysts. These selectivity patterns reflect the combination of electronic and steric effects imposed by the larger aromatic substituent at the carbonyl carbon atom and its concerted interactions with the Lewis acid site, which causes rates for nucleophilic attack of enolates to benzaldehyde to be far less than those to propanal.

Accelerated Keto–Enol Tautomerization Kinetics of Malonic Acid in Aqueous Droplets

Chemical reactions in atmospheric organic aerosol (OA) add large uncertainties to accurate predictions of the effect of aerosol on health, visibility, and climate. The acceleration of reaction rates of organic compounds in droplets compared to bulk solution has been reported; however, the mechanism and the principle of acceleration largely remains unknown. Malonic acid (MA) is a dicarboxylic acid that exhibits keto–enol tautomerization and is ubiquitous in organic aerosols found in the nature. An environment controlled electrodynamic balance (EDB) coupled with Mie scattering imaging (MSI) and Raman spectroscopy was used to levitate single charged MA droplets and investigate the effect of relative humidity (RH: 90%, 70%, 50%, and 30%) and size (28–91 μm diameter) on the reaction kinetics of keto–enol tautomerization of MA. Raman spectroscopy of hydrogen–deuterium isotopic exchange in MA droplets enabled quantitative analysis of MA tautomerization kinetics. The result showed slower reaction rates of MA droplets at lower RH as well as in larger-sized droplets. Application of a step-by-step isotopic exchange model to the MA droplets at 90% RH condition was used to determine the enolization rate of MA, yielding a value 10-fold higher than determined in bulk solution. Keto and enol forms of MA have distinctive physicochemical properties, such as reactivity and hydrogen bond structure. The result from our work suggests that keto–enol tautomerization can play an important role for aging of MA-containing OA in nature, as the enol form of MA can undergo accelerated chemical reactions due to the presence of the reactive carbon–carbon double bond.

Enolization rates control mono- versus di-fluorination of 1,3-dicarbonyl derivatives.

Fluorine-containing 1,3-dicarbonyl derivatives are essential building blocks for drug discovery and manufacture. To understand the factors that determine selectivity between mono- and di-fluorination of 1,3-dicarbonyl systems, we have performed kinetic studies of keto-enol tautomerism and fluorination processes. Photoketonization of 1,3-diaryl-1,3-dicarbonyl derivatives and their 2-fluoro analogues is coupled with relaxation kinetics to determine enolization rates. Reaction additives such as water accelerate enolization processes, especially of 2-fluoro-1,3-dicarbonyl systems. Kinetic studies of enol fluorination with Selectfluor™ and NFSI reveal the quantitative effects of 2-fluorination upon enol nucleophilicity towards reagents of markedly different electrophilicity. Our findings have important implications for the synthesis of α,α-difluoroketonic compounds, providing valuable quantitative information to aid in the design of fluorination and difluorination reactions.

P-Chloroacetophenone: A study of enolization kinetics

ABSTRACTThe reaction rate of enolization of p-chloroacetophenone has been studied in the presence of amino acids, namely, β-alanine, DL-alanine, L-alanine, and glycine. Maximum reaction rate was observed in the case of β-alanine at 22M concentration. The effects of parameters such as effect of ketone concentration, effect of dielectric constant, effect of catalysts, etc., have been found to exert a significant effect on the reaction rate. The effect of temperature was studied in the range of 313–328 K, and several thermodynamic parameters such as entropy (ΔS≠), enthalpy (ΔH≠), energy of activation (ΔEa), and Gibbs free energy (ΔF≠) were found to be −10.32 e.u., 17.87 cal mol−1, 19.24 kcal mol−1, and 21.20 cal mol−1, respectively. The reaction rate increased from 1.9 to 5.8 min−1 on increasing the percentage of dimethylformamide from 10 to 50% (v/v).

New Insight into and Characterization of the Aqueous Metal-Enol(ate) Complexes of (Acetonedicarboxylato)copper.

Nearly 50 years have passed since the classic studies by Larson and Lister [LarsonD. W.; ListerM. W.Can. J. Chem.1968, 46, 823]and Hay and Leong [HayR. W.; LeongK. N.J. Chem. Soc. A1971, 0, 3639]on the copper-catalyzed decarboxylation of acetonedicarboxylic acid (H3Acdica). Although the authors laid the foundations for what we know about this reaction; still very little information exists regarding the underlying aqueous metal-enol(ate)s of (acetonedicarboxylato)copper. In this study, UV–visible titrations revealed three pK values, pK[Cu(H2A)], pK[Cu(HA)], and pK[Cu(A)]. We associated the first two with ionization of α-carbon CH2 groups in [CuII(H2Acdica)keto]1+ and [CuII(HAcdica)keto]0 to form unstable metal-enolates, {[CuII(HAcdica)enolate]} and {[CuII(Acdica)enolate]}, which through β-carbonyl oxygen protonation can form metal-enols [CuII(H2Acdica)enol]1+ and [CuII(HAcdica)enol]0. The square-planar CuII center (electron paramagnetic resonance results) plays a dual role of stabilizing negative electron density at the β-carbonyl oxygen and as an electron sink in [[CuI(HAcdica)enolate]0]‡ and [[CuI(Acdica)enolate]1–]‡ (confirmed through cyclic voltammetry as two single 1e– transfers). The π → π* transition associated with [CuII(HAcdica)enol]0 was used to determine pK[Cu(A)] (deprotonation of enol OH) and enolization rate constant (stopped-flow spectroscopy) but also exhibited a time-dependent decrease in absorbance (on the order of min–1), suggesting a new method to possibly obtain experimental values for the estimated “kCuL” decarboxylation rate constant of metal-enolate [CuL]1– calculated by Larson and Lister. On the basis of our results, we postulate that decarboxylation takes place primarily through {[CuII(HAcdica)enolate]} and [CuII(HAcdica)enol]0. These results add to our understanding of aqueous metal-enol(ate)s, which contain underlying CuII/I redox chemistry, “active methylenes” and enol tautomers and enolate anions, which play roles in many catalytic reactions of interdisciplinary importance.

Enolisation Kinetics of m-Nitro Acetophenone

m-Nitroacetophenone was chosen for the study of kinetics of enolisation. The rate of the reaction was studied by iodination. The kinetics of the reaction was monitored under several conditions of variation of ketone concentration, dielectric constant of the medium , temperature, effect of catalyst etc. In addition to this four different amino acids viz. β-alanin, DL-alanin, L-alanin and Glycine were tested as catalyst for the enolisation process. The rate of enolisation was found to increase with the increase in then ketone concentration , percentage composition of the solvent mixture and also with the increase in the dipole moments of the amino acids. Pseudofirst order rate kinetics was operational and the rate constants were found to increase with the increase in the amino acid molarity. Linear plots obtained for log of rate constants versus reciprocal of temperature which were in good agreement with Arrhenius equation. The values of thermodynamic parameters like Entropy (∆S≠) , Enthalpy (∆H≠), energy of activation (∆Ea) and Free energy(∆F≠) were calculated and were found to be 2.6186 e.u. , 20.85 e.u. ,23.46 k cal mol-1 and 20.0 k cal mol-1 respectively. © 2014 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0)

Kinetics of Enolisation of Acetophenone and p-Bromoacetophenone: Comparative Studies

Biomolecules (Amino Acids) have been used as catalysts for the study of kinetics involved in enolosation of acetophenone and p-bromoacetophenone, and comparative study has been carried out. The process of enolisation was studied by halogenations reactions using iodine. The stoichiometery was determined in each case and the kinetic reactions were carried out to study the effect of catalyst and temperature. The enolisation process was investigated as a bimolecular reaction. The rate of enolisation was of the order p- Bromoacetophenone > Acetophenone depending on the type of substituent. The process was investigated to follow Arrhenius equation. Values for various thermodynamic parameters like Entropy (∆S≠) and Enthalpy (∆H≠) were found to be -2.126 e.u. & -10.88 e.u. and 19.06 K. cal mol-1 & 19.01 K. cal mol-1 for acetophenone and p-bromoacetophenone respectively. © 2013 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0)

Photothermal Tautomerization of a UV Sunscreen (4-tert-Butyl-4′-methoxydibenzoylmethane) in Acetonitrile Studied by Steady-State and Laser Flash Photolysis

The photothermal tautomerization processes between enol and keto forms of 4-tert-butyl-4'-methoxydibenzoylmethane (trade name, Avobenzone) in acetonitrile have been studied by steady-state and laser flash photolysis. The keto form is produced upon photolysis of the enol in only acetonitrile with a quantum yield of 0.014. The molar absorptivity of the keto form was determined. Phototautomerization from the keto to the enol form was not seen. Laser flash photolysis of the keto form recognized the formation of the triplet state. In the dark, the keto form underwent thermal tautomerization to the enol with a lifetime of 5.1 h at 295 K. The enolization rate in acetonitrile was not accelerated by the presence of alcohols and/or water but increased with increasing temperature and followed the Arrhenius expression. The activation energy and the frequency factor were determined for the enolization process from the keto to the enol form. On the basis of the energy states of the tautomers and isomers as estimated by DFT calculations, a schematic energy diagram was determined for the photothermal tautomerization processes in acetonitrile.

What Is Happening When the Blue Bottle Bleaches: An Investigation of the Methylene Blue-Catalyzed Air Oxidation of Glucose

An investigation of the Blue Bottle Experiment, a well-known lecture demonstration reaction involving the dye-catalyzed air oxidation of a reducing sugar in alkaline solution, has delineated the sequence of reactions leading to the bleaching of the dye, the regeneration of color, and so forth. Enolization of the sugar is proposed as a key step in the sequence. The first-order rate constant for this step was found to be ∼2.3 × 10–3 min–1 with respect to total sugar concentration under the conditions used (0.184 M glucose, pH 13.3, 25 °C). Measurements with an oxygen-sensing electrode on Blue-Bottle mixtures containing varying quantities of methylene blue indicated that in a usual demonstration the rate of O2 consumption is ∼60% of the enolization rate. Small samples of the organic oxidation product were isolated and found by chromatographic and NMR-spectroscopic examination to consist primarily of the 5-carbon sugar acid arabinonic acid.

ChemInform Abstract: Asymmetric α‐Hydroxy Ketone Synthesis by Direct Ketone Oxidation Using a Bimetallic Palladium(II) Complex.

Abstract The oxidation of ketones by a chiral bimetallic palladium(II) complex in the presence of CuCl 2 in THF–water solvents gave an enantioselective synthesis of α-hydroxyketones in catalytic oxidation utilizing an atmosphere of oxygen. The ee’s ranged from 61% to 92%. The reaction was accelerated by addition of strong acid that presumably increases the rate of enolization.

Asymmetric α-hydroxy ketone synthesis by direct ketone oxidation using a bimetallic palladium(II) complex

The oxidation of ketones by a chiral bimetallic palladium(II) complex in the presence of CuCl2 in THF–water solvents gave an enantioselective synthesis of α-hydroxyketones in catalytic oxidation utilizing an atmosphere of oxygen. The ee’s ranged from 61% to 92%. The reaction was accelerated by addition of strong acid that presumably increases the rate of enolization.

The evidence for the occurrence of tautomeric structures for selected aldehydes and thioaldehydes

Mass spectra of selected aldehydes and thioaldehydes have been analyzed and specific fragmentation assignments have been done to keto and enol tautomers, although many peaks can be assigned to both forms (i.e. mass spectra are superimposed on one another). The enolization rate for aldehydes is generally favored by the increase in the steric effect caused by α substitution to the carbonyl group. The analysis of the corresponding mass spectra has allowed to establishing an acceptable correlation between selected ion abundances ratios and approximate enolization equilibrium constants (carried out by means of DFT calculations). The influence of temperature on the enol/keto selected fragments abundance ratios (for different aldehydes and thioaldehydes and for different pair of ions of the same compound whenever possible) is studied in order to estimate the enthalpy difference for the tautomeric equilibria. The results indicate that the thioketo–thioenol equilibrium can be studied by mass spectrometry and the ionization in the ion source have negligible effect on the position of that equilibrium.

Kinetic studies on resorcinol-bromate-manganese(II) ion oscillator with and without additives

The present work pertains to the effect of temperature on the oscillatory behavior of bromate driven, Manganese (II) ion catalyzed BZ reaction with aromatic substrate i.e. resorcinol under batch conditions in 1.3 M sulfuric acid as aqueous acid medium. In order to study the effect of methyl ketones as additives (co-substrates), acetone is added to the aforesaid reaction system and the oscillations of the mixed substrate systems were studied at different temperatures. Further the effect of temperature with respect to ternary systems comprising of acetone with other ketones like butanone, pentanone, hexanone and acetyl acetone in 1:1 (v/v) ratio is also studied. It is found that temperature has a marked influence on the reactivity of the reaction systems, with and without methyl ketones and at all concentrations of the additives. Moreover, the rate of enolization of ketones also affects the oscillatory parameters like t in and t p. Although the exact values of enolization constants for the methyl ketones are not known to us, but by studying the oscillatory behavior, a trend can be predicted. Further the formation of end products in the ternary systems is influenced due to hydrophobic interactions of the ketones.

Mechanistic aspects of rearrangement of 16α-hydroxy-17-keto steroids to the 17β-hydroxy-16-keto isomers

The mechanistic aspects of the alkali-catalyzed rearrangement of 16α-hydroxy-17-keto steroid 1 to 17β-hydroxy-16-keto steroid 2 are elucidated by use of 18O- and deuterium-labeling experiments. The 18O-labeling experiments refute the gem-hydration-quasi-diaxial dehydration mechanism for the rearrangement previously proposed and support the conventional enolization mechanism. Moreover, equilibrium by gem-hydration–dehydration occurs at the C-17 carbonyl more efficiently than at the C-16 carbonyl. Enolization rate of a carbonyl group at C-16 of 17β-ketol 2 toward the C-17 position ( k 16,17) was about 8–10 times higher than those of 16α-ketol 1 toward the C-16 position ( k 17,16) and ketol 2 toward the C-15 position ( k 16,15). The marked deuterium-isotope effect on each enolization was observed with k H/ k D ranging between 5.4 and 8.8. The present findings reveal that the initial hydration–dehydration equilibration at the C-17 carbonyl of ketol 1 followed by enolization of the carbonyl gives the ene–diol intermediate that isomerizes quantitatively to the 16-keto isomer of which the 16-carbonyl moiety enolizes preferentially toward the C-17 position rather than the C-15 position, yielding the ene–diol. Computational calculations of ground state energies of ketols 1-M and 2-M, trans-cyclohexane/cyclopentane structures, and their activation energies in the rearrangement support the dynamic aspects of the rearrangement as well as the kinetics data of the enolization.

The 2-Oxocyclobutanecarboxylic Acid Keto−Enol System in Aqueous Solution: A Remarkable Acid-Strengthening Effect of the Cyclobutane Ring

Flash photolysis of 2-diazocyclopentane-1,3-dione in aqueous solution produced 2-oxocyclobutylideneketene, which underwent hydration to the enol of 2-oxocyclobutanecarboxylic acid; the enol then isomerized to the keto form of this acid. Rates of the ketene and enol reactions were measured in acid, base, and buffer solutions across the acidity range [H+] = 10(-1)-10(-13) M, and analysis of these data, together with rates of enolization of the keto form of 2-oxocyclobutanecarboxylic acid determined by bromine scavenging, gave keto-enol equilibrium constants as well as acidity constants of the keto and enol forms. The keto-enol equilibrum constants proved to be 2 orders of magnitude less than those reported previously for the next higher homolog, 2-oxocyclopentanecarboxylic acid, reflecting the difficulty of inserting a carbon-carbon double bond into a small, strained carbocyclic ring. The acidity constant of the enol group of 2-oxocyclobutanecarboxylate ion, on the other hand, is greater, by 4 orders of magnitude, than that of the corresponding enol in the cyclopentyl system. This remarkable increase in acidity with diminishing ring size is consistent with the enhanced s character of the orbitals used to make the exocyclic bonds of the smaller cyclobutane ring.

The 2-oxo-3,3,5,5-tetramethylcyclopentanecarboxylic acid keto–enol system in aqueous solution — Generation of the enol by flash photolytic Wolff rearrangement of 2-diazo-4,4,6,6-tetramethylcyclohexane-1,3-dione followed by hydration of the acylketene thus formed

Flash photolysis of 2-diazo-4,4,6,6-tetramethylcyclohexane-1,3-dione in aqueous solution produced 2-oxo-3,3,5,5-tetramethylcyclopentylideneketene, which underwent hydration to the enol of 2-oxo-3,3,5,5-tetramethylcyclo pentanecarboxylic acid; the enol then isomerized to the keto form of the acid. Rates of hydration of the ketene and rates of ketonization of the enol were measured in perchloric acid, sodium hydroxide, and buffer solutions, and rate profiles were constructed. Rates of enolization of 2-oxo-3,3,5,5-tetramethylcyclopentanecarboyxlic acid were also measured, using bromine to scavenge the enol as it formed, and rates of enolization and ketonization were then combined to give the keto–enol equilibrium constant pKE = 1.65. This and other results are discussed in comparison with the behavior of the unmethylated 2-oxocyclopentanecarboxylic acid system.Key words: flash photolysis, photo-Wolff reaction, ketene hydration, enolization, ketonization, keto–enol equilibria, β-oxocarboxylic acids.

Utility of Acetyldithio-CoA in Detecting the Influence of Active Site Residues on Substrate Enolization by 3-Hydroxyl-3-methylglutaryl-CoA Synthase

Hydroxymethylglutaryl-CoA synthase-catalyzed condensation of acetyl-CoA with acetoacetyl-CoA requires enolization/carbanion formation from the acetyl C-2 methyl group prior to formation of a new carbon-carbon bond. Acetyldithio-CoA, a readily enolizable analog of acetyl-CoA, was an effective competitive inhibitor of avian hydroxymethylglutaryl-CoA synthase (Ki = 28 microm). In the absence of cosubstrate, enzyme catalyzed the enolization/proton exchange from the C-2 methyl group of acetyldithio-CoA. Mutant enzymes that exhibited impaired formation of the covalent acetyl-S-enzyme reaction intermediate exhibited diminished (D159A and D203A) or undetectable (C129S) rates of enolization of acetyldithio-CoA. The results suggest that covalent thioacetylation of protein, which has not been detected previously for other enzymes that enolize this analog, occurs with hydroxymethylglutaryl-CoA synthase. Enzyme catalyzed the transfer of the thioacetyl group of this analog to 3'-dephospho-CoA suggesting the intermediacy of a covalent thioacetyl-S-enzyme species, which appears to be important for proton abstraction from C-2 of the thioacetyl group. Avian enzyme glutamate 95 is crucial to substrate condensation to form a new carboncarbon bond. Mutations of this invariant residue (avian enzyme E95A and E95Q; Staphylococcus aureus enzyme E79Q) correlated with diminished ability to catalyze enolization of acetyldithio-CoA. Enolization by E95Q was not stimulated in the presence of acetoacetyl-CoA. These observations suggest either a direct (proton abstraction) or indirect (solvent polarization) role for this active site glutamate.

3 Alkali and alkaline-earth metals

Highlights this year include an explanation of the 300-fold decrease in the rate of amine-assisted enolization of 2-methylcyclohexanone when Bun3N is replaced by Bun2(Bui)N, the first alkaline earth alkalide, the first monomeric butyllithium compound, the first bond between beryllium and a Group 14 element other than carbon and the first terminally bonded aryloxo compounds of magnesium.

Ketone enolization by lithium hexamethyldisilazide: structural and rate studies of the accelerating effects of trialkylamines.

Mechanistic studies of the enolization of 2-methylcyclohexanone mediated by lithium hexamethyldisilazide (LiHMDS; TMS2NLi) in toluene and toluene/amine mixtures are described. NMR spectroscopic studies of LiHMDS/ketone mixtures in toluene reveal the ketone-complexed cyclic dimer (TMS2NLi)2(ketone). Rate studies using in situ IR spectroscopy show the enolization proceeds via a dimer-based transition structure, [(TMS2NLi)2(ketone)]++. NMR spectroscopic studies of LiHMDS/ketone mixtures in the presence of relatively unhindered trialkylamines such as Me2NEt reveal the quantitative formation of cyclic dimers of general structure (TMS2NLi)2(R3N)(ketone). Rate studies trace a >200-fold rate acceleration to a dimer-based transition structure, [(TMS2NLi)2(R3N)(ketone)]++. Amines of intermediate steric demand, such as Et3N, are characterized by recalcitrant solvation, saturation kinetics, and exceptional (>3000-fold) accelerations traced to the aforementioned dimer-based pathway. Amines of high steric demand, such as i-Pr2NEt, do not observably solvate (TMS2NLi)2(ketone) but mediate enolization via [(TMS2NLi)2(R3N)(ketone)]++ with muted accelerations. The most highly hindered amines, such as i-Bu3N, do not influence the LiHMDS structure or the enolization rate. Overall, surprisingly complex dependencies of the enolization rates on the structures and concentrations of the amines derive from unexpectedly simple steric effects. The consequences of aggregation, mixed aggregation, and substrate-base precomplexation are discussed.

The 2-oxocyclohexanecarboxylic acid keto-enol system in aqueous solution.

Flash photolysis of 2-diazocycloheptane-1,3-dione or 2,2-dimethyl-5,6,7,8-tetrahydrobenzo-4H-1,3-dioxin-4-one in aqueous solution produced 2-oxocyclohexylideneketene, which underwent hydration to the enol of 2-oxocyclohexanecarboxylic acid, and the enol then isomerized to the keto form of the acid. Isomerization of the enol to keto forms was also observed using solid enol, a substance heretofore commonly believed to be the keto acid. Rates of ketonization were measured in perchloric acid, sodium hydroxide, and buffer solutions, and a ketonization rate profile was constructed. Rates of enolization of the keto acid were also measured using bromine to scavenge the enol as it formed. Rates of enolization and ketonization were then combined to provide the keto-enol equilibrium constant pK(E) = 1.27. This and some of the other results obtained are different from the corresponding quantities for the 2-oxocyclopentanecarboxylic acid keto-enol system. These differences are discussed.