288-32-4Relevant articles and documents
Relation of the Transition-State Structure for the Water-Catalyzed Hydrolysis of 1-Acetylimidazolium Ion to Solvent Hydrophobicity: Proton Inventories in Water-Acetonitrile Mixtures
Huskey, William P.,Hogg, John L.
, p. 53 - 59 (1981)
The transition-state structure for the water-catalyzed hydrolysis of 1-acetylimidazolium ion has been probed in solvent systems which may mimic the hydrophobic nature of an enzyme's active site.The kinetic solvent deuterium isotope effect kH2O/kD2O, are 2.58, 2.49, and 2.10 in water, in 0.5 vol fraction of acetonitrile in water, and in 0.9 vol fraction of acetonitrile in water, respectively.The proton inventory investigations suggest all three solvent system entertain a transition-state structure composed of a catalytic proton bridge between the reorganizing substrate and a water molecule acting as a general base-catalyst.A "compression" of the transition-state structure in the solvent system containing the largest amount of acetonitrile is suggested to be responsible for the diminished kinetic solvent deuterium isotope effect.The reaction has been shown to be second order with respect to water.
Enthalpy Changes Accompanying Hydrolysis of 3-(2-Furyl)acryloylimidazole by α-Chymotrypsin
Slightom, J. L.,Bolen, D. W.
, p. 6318 - 6324 (1980)
A calorimetric analysis of the α-chymotrypsin-mediated hydrolysis of 3-(2-furyl)acryloylimidazole at pH 7.85 is presented and compared with the nonenzymatic hydrolysis.The enzyme-mediated hydrolysis is characterized by an apparent pKα for acylation of 6.60 and a deacylation pKα of 7.55.Activation enthalpy changes of 7.8+/-1.3 and 15.0+/-0.4 kcal/mol were determined for acylation (k2) and deacylation (k3), respectively.An enthalpy change of 0.04+/-0.85 kcal/mol for Michaelis complex formation was also determined from the temperature dependence of Ks.Heats of acylation (-10.1+/-0.2 kcal/mol) and deacylation (-1.2+/-0.55 kcal/mol) corrected for buffer ionization and product ionization heats were separately determined by making use of the large rate difference between acylation and deacylation (k2=1000k3) which exists at pH 7.85.The sum of these corrected enthalpy changes (-11.3+/-0.6 kcal/mol) agrees very well with the enthalpy change observed for nonenzymatic hydrolysis of furylacryloylimidazole (-11.3+/-0.5 kcal/mol) and validates the approach used.
Catalysis of the methanolysis of acetylimidazole by lanthanum triflate
Neverov, Alexei A.,Brown
, p. 1247 - 1250 (2000)
Methanolysis of acetylimidazole (1) and N-acetylimidazolepentamine-Co(III) (2) was found to be markedly accelerated in the presence of La(OTf)3. Potentiometric titration of a solution of La3+(OTf-)3 gave a pKa for the metal bound CH3OH of 7.22. The kinetics of methanolysis of 1 and 2 were measured at 25°C at various pH under buffered conditions as a function of increasing La3+. Analysis of both the kinetic and potentiometric data indicates that the catalytically active species is a La3+-dimer, bridged by two methoxides, (CH3OH)nLa3+(CH3O-) 2La3+(CH3OH)n. The maximum second-order rate constants for attack of the dimer on 1 and 2 are 1.50 × 103 M-1 s-1 and 1.42 × 102 M-1 s-1 respectively and both processes adhere to titration of a La3+(CH3OH) to generate the active form. The results are explained in terms of a mechanism where the methoxy-bridged La3+ dimer transiently breaks a La3+-OCH3 bond to expose both a CH3O- nucleophile and a La3+ which can act as a Lewis acid. Unlike the situation in water, the methanol results indicate that the medium greatly stabilizes and solubilizes the active dimer without the necessity of creating specially designed ligands to stabilize the dinuclear core.
Synthesis of 1-alkylimidazoles
Gridnev,Mihaltseva
, p. 1547 - 1555 (1994)
A mechanistic investigation of the synthesis of imidazole and 1- alkylimidazoles has led to an improved synthesis starting from glyoxal, formaldehyde and alkylammonium chlorides.
The stability of N, N -carbonyldiimidazole toward atmospheric moisture
Engstrom, Kenneth M.,Sheikh, Ahmad,Ho, Raimundo,Miller, Robert W.
, p. 488 - 494 (2014)
N,N-Carbonyldiimidazole (CDI) is known to be sensitive to degradation by atmospheric moisture. This work details some mechanistic aspects of CDI degradation by atmospheric moisture along with the major contributing factors to degradation rate. Also, several analytical techniques for the measurement of CDI purity that are less cumbersome than the traditional gas-capture assay are described.
Lc and nmr studies for identification and characterization of degradation byproducts of olmesartan acid, elucidation of their degradation pathway and ecotoxicity assessment
Di Fabio, Giovanni,Libralato, Giovanni,Luongo, Giovanni,Previtera, Lucio,Saviano, Lorenzo,Serafini, Sara,Siciliano, Antonietta,Zarrelli, Armando
, (2021)
The discovery of various sartans, which are among the most used antihypertensive drugs in the world, is increasingly frequent not only in wastewater but also in surface water and, in some cases, even in drinking or groundwater. In this paper, the degradation pathway of olmesartan acid, one of the most used sartans, was investigated by simulating the chlorination process normally used in a wastewater treatment plant to reduce similar emerging pollutants. The structures of nine isolated degradation byproducts (DPs), eight of which were isolated for the first time, were separated via chromatography column and HPLC methods, identified by combining nuclear magnetic resonance and mass spectrometry, and justified by a proposed mechanism of formation beginning from the parent drug. Ecotoxicity tests on olmesartan acid and its nine DPs showed that 50% of the investigated byproducts inhibited the target species Aliivibrio fischeri and Raphidocelis subcapitata, causing functional decreases of 18% and 53%, respectively.
Development of a method for the quantification of clotrimazole and itraconazole and study of their stability in a new microemulsion for the treatment of sporotrichosis
Ferreira, Patricia Garcia,de Souza Lima, Carolina Guimar?es,Noronha, Letícia Lorena,de Moraes, Marcela Cristina,de Carvalho da Silva, Fernando,Vi?osa, Alessandra Lifsitch,Futuro, Débora Omena,Ferreira, Vitor Francisco
, (2019)
Sporotrichosis occurs worldwide and is caused by the fungus Sporothrix brasiliensis. This agent has a high zoonotic potential and is transmitted mainly by bites and scratches from infected felines. A new association between the drugs clotrimazole and itraconazole is shown to be effective against S. brasiliensis yeasts. This association was formulated as a microemulsion containing benzyl alcohol as oil, Tween 60 and propylene glycol as surfactant and cosurfactant, respectively, and water. Initially, the compatibility between clotrimazole and itraconazole was studied using differential scanning calorimetry (DSC), thermogravimetric analysis (TG), Fourier transform infrared spectroscopy (FTIR), and X-ray powder diffraction (PXRD). Additionally, a simple and efficient analytical HPLC method was developed to simultaneously determine the concentration of clotrimazole and itraconazole in the novel microemulsion. The developed method proved to be efficient, robust, and reproducible for both components of the microemulsion. We also performed an accelerated stability study of this formulation, and the developed analytical method was applied to monitor the content of active ingredients. Interestingly, these investigations led to the detection of a known clotrimazole degradation product whose structure was confirmed using NMR and HRMS, as well as a possible interaction between itraconazole and benzyl alcohol.
KINETICS OF FORMATION OF THE ELECTON DONOR-ACCEPTOR COMPLEX BETWEEN IODINE AND IMIDAZOLE IN CHLOROBUTANE SOLUTION
Caldin, Edward,Field, John P.
, p. 1937 - 1942 (1982)
The kinetics of the formation of the electron donor-acceptor complex between iodine and imidazole in 1-chlorobutane at -64 deg C have been investigated by an improved microwave temperature-jump apparatus.The forward rate constant kf is (3.3+/-0.4)x1E9 dm3 mol-1 s-1.This is nearly the same as the diffusion-controlled value kD calculated from the simple Smoluchowsky model for reaction at every encounter between spherical molecules, without geometrical requirements, in a homogeneous fluid (kf/kD=0.8).
EFFECT OF THE SURFACE AREA OF PLATINUM ON THE ACTIVITY OF A BIFUNCTIONAL ALUMINOPLATINUM CATALYST IN THE SYNTHESIS OF ALKYLIMIDAZOLES FROM DIAMINES AND CARBONYL ACIDS
Gitis, K. M.,Raevskaya, N. I.,Zaitsev, A. V.,Borovkov, V. Yu.,Kozan, S. B.,Isagulyants, G. V.
, p. 1547 - 1550 (1992)
An investigation has been conducted into the effect of the acid and dehydrogenating functions of an aluminoplatinum catalyst on the synthesis of 2-methylimidazole from ethylenediamine and acetic acid.It has been established that formation of the intermediate 2-methylimidazoline involves the acid Al2O3 centers and its rate of formation is greater than the rate of its subsequent dehydrogenation to 2-methylimidazole on the Pt centers.The symbatic nature of the variations in the 2-methylimidazole yield and the surface area of the platinum in the aluminoplatinum catalyst has been demonstrated.Keywords: C-alkylimidazoles, 2-methylimidazole, aluminoplatinum catalyst.
Rate-Limiting Deprotonation in Tetrahedral Intermediate Breakdown
McClelland, Robert A.
, p. 7579 - 7583 (1984)
A kinetic study in acetate and formate buffers is reported of the breakdown to β-hydroxyethyl benzoate of the hemiorthoester-type tetrahedral intermediate 2-phenyl-2-hydroxy-1,3-dioxolane.This species is generated as a transient intermediate in acid solutions in the hydrolysis of the amide acetals 2-phenyl-2-(dimethylamino)-1,3-dioxolane and 2-phenyl-2-(1-imidazolyl)-1,3-dioxolane.Plots of observed rate constant vs. buffer concentration exhibit pronounced curvature in dilute buffers suggestive of a change in rate-limiting step with changing buffer concentration.A mechanism is proposed involving deprotonation of the hydroxy group of the hemiorthoester to produce a highly reactive anion.In the absence of buffer and in very dilute buffers the deprotonation step is rate limiting, the anionic hemiorthoester going on to product at a rate faster than it is reprotonated.In more concentrated buffers the deprotonation step becomes reversible because of the availability of the acid component of the buffer for the reprotonation.A kinetic analysis is presented, providing a rate constant of approximately 5 x 107 s-1 for breakdown of the anionic hemiorthoester.This intermediate is comparable to that which would be encountered during the hydrolysis of a benzoate ester, and some consequences of the large reactivity are discussed.This is suggested to be a contributing factor behind the small amount of carbonyl (18)O exchange observed during the base hydrolysis of esters.It is also pointed out that with leaving groups significantly better than alcoxide, the lifetime may become so short that the tetrahedral intermediate anion could not exist.In this case an acyl transfer reaction proceeding via this anion would have to be regarded as being concerted with the anion as a transition state, not an intermediate.
