Hydration of the carbonyl group — Acetic acid catalysis in the co-operative mechanism

2005 ◽  
Vol 83 (6-7) ◽  
pp. 769-785 ◽  
Author(s):  
Yih-Huang Hsieh ◽  
Noham Weinberg ◽  
Kiyull Yang ◽  
Chan-Kyung Kim ◽  
Zheng Shi ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Carbonyl Group ◽  
Isotope Shift ◽  
Acid Catalysis ◽  
Water Molecules ◽  
Hydration Reaction ◽  
Water Solvent ◽  
General Acid ◽  
O Isotope ◽  
Acid Catalyzed

In a co-operative reaction, solvent molecules, specifically water molecules, participate actively in the mechanism to circumvent the formation of charged intermediates. This paper extends our earlier theoretical treatment of the neutral co-operative hydration of acetone to include general acid catalysis by acetic acid. As before, the predominant neutral channel employs three catalytic water molecules. The principal acetic acid catalyzed channels employ one catalytic water molecule and, in approximately equal proportions, one or both oxygens of the carboxyl group. The theoretical rate constant for general acid catalysis is calculated to be 0.49 M–1 s–1 at 298 K. This compares to an estimated experimental value of 0.30 M–1 s–1 for acetic acid catalyzed hydration of acetone at 298 K in water solvent, determined by using the 18O-isotope shift in the 13C NMR spectrum of 2-13C-labelled acetone as a kinetic probe. It is concluded that the notion of co-operativity can be extended to include general acid catalysis of the hydration of a carbonyl group in water solvent. This creates an obvious problem for the generally accepted view that multistep ionic mechanisms are operative in the low dielectric media that exist at the active sites of hydrolytic enzymes. The relevance of this finding to the mechanisms of action of β-lactam antibiotics has been noted.Key words: hydration, reaction mechanism, co-operativity, general acid catalysis, ab initio, SCRF, 18O-isotope shift.

Deuterium exchange of C-methyl protons in lumazine derivatives

1970 ◽  
Vol 48 (2) ◽  
pp. 263-270 ◽  
Author(s):  
J. M. McAndless ◽  
Ross Stewart
Keyword(s):  
Proton Magnetic Resonance ◽  
Proton Magnetic Resonance Spectroscopy ◽  
Acid Catalysis ◽  
Deuterium Exchange ◽  
Base Catalysis ◽  
Resonance Spectroscopy ◽  
Methyl Group ◽  
General Base ◽  
General Acid ◽  
Acid Catalyzed

Proton magnetic resonance spectroscopy has been used to examine the deuterium exchange of the methyl protons in two lumazine derivatives. The exchange occurs at the C-7 methyl group in 6,7,8-trimethyllumazine (2) and at the C-6 methyl group in 1,7-dihydro-6,7,8-trimethyllumazine (3). The former reaction is subject to both general acid- and general base-catalysis but the latter only to general acid-catalysis. Plausible mechanisms for the reactions of both compounds are advanced, involving in the case of 3, acid-catalyzed addition of water across the C6—N5 double bond.

The Hydration of Ketones in Mixtures of Water and Polar Aprotic Solvents

1972 ◽  
Vol 50 (13) ◽  
pp. 1992-1999 ◽  
Author(s):  
Ross Stewart ◽  
John D. Van Dyke
Keyword(s):  
Activity Coefficient ◽  
Water Content ◽  
Equilibrium Constant ◽  
Carbonyl Group ◽  
Pure Water ◽  
Solvent Composition ◽  
Water Molecules ◽  
Aprotic Solvents ◽  
Acid Catalyzed

The hydration of a series of ring-substituted trifluoroacetophenones (Z) has been studied by means of u.v. and n.m.r. spectroscopy in DMSO–water and sulfolane–water mixtures. The W0 function is defined as [Formula: see text] where Kd is the equilibrium constant for the reaction [Formula: see text]Mixtures of water and sulfolane in all proportions have a dehydrating effect compared to water but mixtures of water and DMSO down to 15 mol % water are more hydrating with respect to the carbonyl group of trifluoroacetophenones than is pure water. An analysis of activity coefficient behavior indicates that the diol, ZH2O, has a higher requirement for solvation by water molecules than does water itself.The rate of the uncatalyzed hydration in aqueous sulfolane drops drastically as the water content of the medium decreases, whereas the rate of the acid-catalyzed reaction is not greatly affected by changes in the solvent composition; a plot of log k for both catalyzed and uncatalyzed reactions is approximately linear in W0.

Synthesis and thermolysis rate constants of diastereomeric oxadiazoline sources of acetoxy(methoxy)carbene — Reaction of acetoxy(methoxy)carbene with isocyanates

2006 ◽  
Vol 84 (7) ◽  
pp. 927-933 ◽  
Author(s):  
Wojciech Sokol ◽  
John Warkentin
Keyword(s):  
Acetic Acid ◽  
Ethyl Acetate ◽  
Carbonyl Group ◽  
Rate Constants ◽  
Acid Catalysis ◽  
Major Product ◽  
Acetyl Group ◽  
Methyl Pyruvate ◽  
Acetyl Transfer ◽  
Cis And Trans

Oxidation of the methoxycarbonylhydrazone of p-methoxyacetophenone affords both the cis- and trans-2-acetoxy-2-methoxy-5-(p-methoxyphenyl)-5-methyl-Δ3-1,3,4-oxadiazolines (also known as corresponding 2,5-dihydro-1,3,4-oxadiazoles) as well as methyl 1-acetoxy-1-(p-methoxyphenylethyl)diazenecarboxylate. The three isomers were separated and identified by spectroscopic means. Methyl 1-acetoxy-1-(p-methoxyphenylethyl)diazenecarboxylate is the major product from oxidation in dichloromethane. Oxidation in acetic acid did not afford the oxadiazolines but gave the diazenecarboxylate and, in addition, 1-(p-methoxyphenyl)ethyl acetate. Attempts to isomerize the diazenecar boxylate to the oxadiazolines by acid catalysis were not successful. Thermolysis of the oxadiazolines at 50.4 °C occurred with approximately the same rate constant (ca. 3.6 × 10–5 s–1) to afford acetoxy(methoxy)carbene, which rearranges to methyl pyruvate by acetyl transfer. The carbene, which reacts with relatively unhindered isocyanates to transfer the methoxy carbonyl group to carbon and the acetyl group to nitrogen, can be considered an acyl anion equivalent in that reaction.Key words: acetoxy(methoxy)carbene, diazene, oxadiazoline, isocyanate, (acetylamino)oxoacetate.

scholarly journals The neutral hydrolysis of methyl acetate — Part 2. Is there a tetrahedral intermediate?

2009 ◽  
Vol 87 (4) ◽  
pp. 544-555 ◽  
Author(s):  
Zheng Shi ◽  
Yih-huang Hsieh ◽  
Noham Weinberg ◽  
Saul Wolfe
Keyword(s):  
Acetic Acid ◽  
Methyl Acetate ◽  
Acid Catalysis ◽  
Experimental Result ◽  
Acid Product ◽  
General Acid ◽  
One Step ◽  
Hydrolysis Of ◽  
Step Mechanism ◽  
Tetrahedral Intermediates

A computational strategy that reproduces the experimental rates of hydration of formaldehyde, acetaldehyde, acetone, and cyclohexanone and the rates of acetic acid and 2-hydroxypyridine-catalyzed hydration of acetone has been extended to the results of the neutral hydrolysis of methyl acetate reported in Part 1. Calculations have been performed for one-step and two-step mechanisms, with cooperative assistance from one to three additional water molecules in the presence and absence of the acetic acid product. The calculations predict that, for the neutral reaction, a one-step mechanism will be favoured if tetrahedral intermediates have a short lifetime and do not interconvert prior to breakdown (case A), and a two-step mechanism will be operative if tetrahedral intermediates are allowed to interconvert prior to breakdown (case B). The experimental results are consistent with the predictions of case A. In the presence of acetic acid, case A predicts that the acid will contribute only 1.6% to the overall rate, a negligible acceleration over the noncatalytic process, and case B predicts general acid catalysis to be an order of magnitude greater than the experimental result. It is concluded that the neutral hydrolysis of methyl acetate is mainly a cooperative one-step process, and that general acid catalysis by the acetic acid product does not occur.

A KINETIC STUDY OF THE HYDROLYSIS OF BENZALANILINE

1953 ◽  
Vol 31 (4) ◽  
pp. 361-376 ◽  
Author(s):  
A. V. Willi ◽  
R. E. Robertson
Keyword(s):  
Kinetic Study ◽  
Acid Catalysis ◽  
Catalyst Concentration ◽  
Effect Of Substituents ◽  
General Acid ◽  
Acid Catalyzed ◽  
Interesting Special Case ◽  
Hydrolysis Of ◽  
Special Case

The rates of the acid catalyzed hydrolysis of a series of para substituted benzalanilines have been studied in 50/50 methanol–water in the presence of acetate buffers. Special and general acid catalysis were observed. The effect of para substituents on the rate is different for the charged and uncharged catalyst, and Hammett's relation cannot be applied. Similarly the effect of substituents on the Arrhenius constants for the two cases is different. The para dimethylamino derivative provides an interesting special case. For low buffer concentrations and in unbuffered solutions certain deviations were observed which show that the dependence of the rate on the catalyst concentration is more complicated than the equation[Formula: see text]

Solvent effects on kinetics and mechanism of acid-catalyzed decomposition of 1,3-bis(4-methylphenyl)triazene I. Reactions in alcohols

1990 ◽  
Vol 55 (1) ◽  
pp. 147-155 ◽  
Author(s):  
Taťjana Nevěčná ◽  
Oldřich Pytela ◽  
Miroslav Ludwig ◽  
Jaromír Kaválek
Keyword(s):  
Trichloroacetic Acid ◽  
Acid Catalysis ◽  
Acid Catalyst ◽  
Kinetics And Mechanism ◽  
Acid Catalysts ◽  
Effect Of Solvents ◽  
Protic Solvents ◽  
General Acid ◽  
Catalytically Active ◽  
Acid Catalyzed

The effect of protic solvents (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, cyclohexanol) has been studied on the kinetics and mechanism of acid-catalyzed decomposition of 1,3-bis(4-methylphenyl)triazene, using trichloroacetic acid as the acid catalyst. Both the non-dissociated acid and the proton have been found to be catalytically active. The mechanism of splitting of the triazene substrate with the non-dissociated acid involves the general acid catalysis. Comparison of the catalytic rate constants of the two acid catalysts and effect of solvents on these values indicate that the general acid catalysis probably also operates in the reaction of the substrate with proton.

scholarly journals Electrostatic stabilization in a pre-organized polar active site: the catalytic role of Lys-80 in Candida tenuis xylose reductase (AKR2B5) probed by site-directed mutagenesis and functional complementation studies

2005 ◽  
Vol 389 (2) ◽  
pp. 507-515 ◽  
Author(s):  
Regina Kratzer ◽  
Bernd Nidetzky
Keyword(s):  
Carbonyl Group ◽  
Acid Catalysis ◽  
Xylose Reductase ◽  
Site Directed Mutagenesis ◽  
Side Chain ◽  
Linear Free Energy Relationship ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
General Acid ◽  
Group Reduction

Lys-80 of Candida tenuis xylose reductase (AKR2B5) is conserved throughout the aldo–keto reductase protein superfamily and may prime the nearby Tyr-51 for general acid catalysis to NAD(P)H-dependent carbonyl group reduction. We have examined the catalytic significance of side-chain substitutions in two AKR2B5 mutants, Lys-80→Ala (K80A) and Asp-46→Asn Lys-80→Ala (D46N K80A), using steady-state kinetic analysis and restoration of activity with external amines. Binding of NAD+ (Kd=24 μM) and NADP+ (Kd=0.03 μM) was 10- and 40-fold tighter in K80A than the wild-type enzyme, whereas binding of NADH (Kd=51 μM) and NADPH (Kd=19 μM) was weakened 2- and 16-fold in this mutant respectively. D46N K80A bound NAD(P)H and NAD(P)+ uniformly approx. 5-fold less tightly than the wild-type enzyme. The second-order rate constant for non-covalent restoration of NADH-dependent reductase activity (kmax/Kamine) by protonated ethylamine was 0.11 M−1·s−1 for K80A, whereas no detectable rescue occurred for D46N K80A. After correction for effects of side-chain hydrophobicity, we obtained a linear free energy relationship of log (kmax/Kamine) and amine group pKa (slope=+0.29; r2=0.93) at pH 7.0. pH profiles of log (kcat/Km) for carbonyl group reduction by wild-type and D46N K80A revealed identical and kinetically unperturbed pKa values of 8.50 (±0.20). Therefore the protonated side chain of Lys-80 is not an essential activator of general acid catalysis by AKR2B5. Stabilized structurally through the salt-link interaction with the negatively charged Asp-46, it is proposed to pull the side chain of Tyr-51 into the catalytic position, leading to a preorganized polar environment of overall neutral charge, in which approximation of uncharged reactive groups is favoured and thus hydride transfer from NAD(P)H is strongly preferred. Lys-80 affects further the directional preference of AKR2B5 for NAD(P)H-dependent reduction by increasing NAD(P)H compared with NAD(P)+-binding selectivity.

scholarly journals A total synthesis of myrrhine, (±)-hippodamine, and (±)-convergine

1976 ◽  
Vol 54 (3) ◽  
pp. 473-481 ◽  
Author(s):  
William A. Ayer ◽  
Robin Dawe ◽  
Reinhold A. Eisner ◽  
Kimiaki Furuichi
Keyword(s):  
Acetic Acid ◽  
Total Synthesis ◽  
Carbonyl Group ◽  
Acid Catalyzed ◽  
Defensive Substance ◽  
Hydrolysis Of ◽  
Alcohol Reduction

A seven-step, stereoselective, total synthesis of the ladybug defensive substance myrrhine (5) from 2,4,6-collidine is presented. Successive alkylation and acylation of 2,4,6-collidine followed by ketalization provides 2-(3-[2-(1,3-dioxolanyl)]propyl)-6-(2-methyl-2-[1,3-dioxolanyl]methyl)-4-methylpyridine (14). Sodium–alcohol reduction gives the corresponding all-cis piperidine 17. Hydrolysis of 17 followed by acid-catalyzed cyclization provides ketone 26. Reduction of the carbonyl group in 26 gives myrrhine (5). Cyclization using pyrrolidine – acetic acid gives a mixture of ketones (26 and 31). Reduction of 31 gives (±)-hippodamine (4). Oxidation of (±)-hippodamine with peracid gives (±)-convergine (3).

Some Kinetic and Equilibrium Isotope Effects in the Isobutylphenone Eno land Enolate Ion System

1989 ◽  
Vol 44 (5) ◽  
pp. 406-412 ◽  
Author(s):  
Y. Chiang ◽  
A. J. Kresge ◽  
P. A. Walsh
Keyword(s):  
Acetic Acid ◽  
Isotope Effect ◽  
Acid Catalysis ◽  
Isotope Effects ◽  
Kinetic Isotope Effects ◽  
Free Energies ◽  
Kinetic Isotope ◽  
Hydronium Ion ◽  
Acid Catalyzed ◽  
Water Catalysis

The following kinetic isotope effects were determined for acid-catalyzed ketonization of isobutyrophenone enol and enolate ion through rate-determining hydron transfer from catalyst to substrate: enol, kH/kD = 3.30±0.07 (hydronium ion catalysis), kH/kD = 4.0 + 2.8 (acetic acid catalysis); enolate ion, kH/kD= 1.00 + 0.21 (hydronium ion catalysis), kH/kD = 3A \ +0.20 (acetic acid catalysis), kH/kD = 7.48±0.23 (water catalysis). The magnitude of these isotope effects, when assessed in terms of the free energies of reaction for the processes in which they occur, are consistent with Melander-Westheimer- Bigeleisen theory. An equilibrium isotope effect of KH/KD = 5.88±0.32 was also determined for the ionization of isobutyrophenone enol as an oxygen acid.

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