Chloroform Ethyl Acetate Research Articles

A mechanistic viewpoint of the reaction between 1‐fluoro‐2,6‐dinitrobenzene and alicyclic amines in the ethyl acetate–chloroform system

AbstractA study was made of the influence of temperature on the reactions between 1‐fluoro‐2,6‐dinitrobenzene and each of the secondary amines pyrrolidine, piperidine and homopiperidine (hexahydro‐1H‐azepine), carried out in ethyl acetate–chloroform binary solvent mixtures. It involved the analysis of both global activation parameters and the corresponding Arrhenius plots from the kA values at three amine concentrations. These values were obtained by carrying out the reactions at 5, 15, 25, 40 and 50°C over the whole range of chloroform mole fraction. The analysis of Arrhenius lines allowed us to prove the existence of isokinetic relationships, which were used as a diagnostic tool in order to infer a changeover in the nature of the rate‐determining transition state as a function of solvent composition. The experimental evidence together with theoretical quantum mechanical calculations suggest that the reactions with the secondary amines explored carried out in pure ethyl acetate and ethyl acetate–chloroform solvent mixture at X = 0.1 and in some cases also at X = 0.3 proceed via the formation of a six‐membered orientated dipolar aggregate in which the specific base–general acid (SB–GA) mechanism may take place. The reactions carried out in the remaining solvent mixtures evolve towards the classical SB–GA mechanism. Copyright © 2004 John Wiley & Sons, Ltd.

Kinetics of the reactions between 1‐fluoro‐2,6‐dinitrobenzene and pyrrolidine and piperidine in binary solvent systems: Influence of the nucleophile structure

AbstractWe studied the kinetics of the reaction between 1‐fluoro‐2,6‐dinitrobenzene and pyrrolidine or piperidine in ethyl acetate–chloroform or acetonitrile and acetonitrile–chloroform binary solvent mixtures. The kinetic response of these reactions was compared with that of the reactions with homopiperidine. The aim of this work was to evaluate the influence of the nucleophile structure and of solvent effects on those reactive systems. The amine structure has a great influence on second‐order rate constants, especially on the rate constants related to the catalyzed step. In mixtures with chloroform the amine structure is also responsible for the change in the reaction mechanism. Theoretical quantum mechanics calculations confirm that the origin of these results lies in stereoelectronic effects due to the conformational difference between the amino moieties in the intermediate σ adducts as they release the nucleofuge. Solvation effects are dominated by non‐specific interactions. The order of incidence of the molecular–microscopic solvent properties on the second‐order rate coefficient kA is dipolarity/polarizability>hydrogen‐bond donor ability (HBD)>hydrogen‐bond acceptor ability (HBA). The (HBA+HBD) and (HBA+HBA/HBD) solvent systems have similar solvation mechanisms: the critical state is preferentially solvated by the structure formed by intersolvent hydrogen‐bonded species. Mixtures of the type (HBA/HBD+HBD) manifest a particular solvation behavior. Among the reactive systems selected there is only one example in which preferential solvation is not operative. Copyright © 2004 John Wiley & Sons, Ltd.Additional material for this paper is available in Wiley Interscience

Rapid HPTLC Determination of Rosiglitazone in Pharmaceutical Formulations

A new, simple, rapid, and stability‐indicating high‐performance thin layer chromatographic (HPTLC) method has been developed and validated for the determination of rosiglitazone in tablets. Analysis was performed on silica gel 60F254 plates in horizontal chambers with chloroform–ethyl acetate–25% ammonium hydroxide (5:5:0.1, v/v) as mobile phase. Detection and quantification were performed by classical densitometry at 240 and 254 nm. The active substance was extracted from tablets with ethanol. Calibration plots were constructed in the range 0.2–1.0 µg/10 µL and were correlated with good correlation coefficients (r 240 = 0.9993; r 254 = 0.9994). Precision was validated by replicate analyses of standard solutions, and accuracy by analysis of fortified samples. The precision of the proposed chromatographic method, expressed as mean RSD was 3.58 and 2.76% for 240 nm, and 8.23 and 6.56% for 254 nm, for the lowest and the highest calibration levels, respectively. The mean recoveries from the fortified samples ranged from 89.48% to 99.38% for 240 nm, and from 89.05% to 100.89% for 254 nm. The mean recoveries from tablets were 101.95% and 103.2% for assays at 240 and 254 nm, respectively.

Simultaneous Determination of Cefuroxime Axetil and Cefuroxime in Pharmaceutical Preparations by Thin-Layer Chromatography and Densitometry

Conditions have been established for identification and quantification of cefuroxime axetil and cefuroxime by thin-layer chromatography and densitometry. Good separation of these compounds was achieved on silica gel by use of chloroform–ethyl acetate–glacial acetic acid–water, 4:4:4:1 (v/v), as mobile phase. UV densitometry was used to detect spots on chromatograms. Under these conditions the limits of detection for cefuroxime axetil and cefuroxime were 40 ng and 30 ng, respectively. Recoveries of cefuroxime axetil and cefuroxime were 99.93% and 97.94%, respectively.

Analysis of ebastine in pharmaceutical preparations by high-performance thin-layer chromatography

A new simple, precise, rapid, and selective high-performance thin-layer chromatography (HPTLC) method has been developed for the analysis of finasteride in pharmaceutical formulations. The method uses loratadine as an internal standard. The stationary phase was silica gel 60F 254 prewashed with methanol; chloroform-ethyl acetate, 6 + 4 (v/v) was used as mobile phase. Detection and quantification were performed densitometrically at λ = 228 nm. The linear range of the analysis was 0.2-2.0 pg and the percentage recovery was 101.8%.

Synthesis of 25,26,27- tris (Ethoxycarbonylmethoxy)-28-(substituted Oxy-carbonylmethoxy) Calix-4-arene: First Example of Calix-imidazole/Benzimidazole Analog

Synthesis of calix-imidazole/benzimidazole analog i.e., 25,26, 27-tris-(ethoxycarbonylmethoxy)-28-({2′-phenylcarbamoyl} benzimidazolyloxycarbonylmethoxy) calix-4-arene. 6a, 25,26,27-tris- (ethoxycarbonylmethoxy)-28-({2″-phenylcarbamoyl} 4′,5′-dihydroimidazolyloxy-carbonylmethoxy) calix-4-arene. 6b and 25,26,27-tris-(ethoxycarbony-methoxy) calix-4-arene 6c have been described. Structure elucidation explains the interaction of substituted imidazole/benzimidazole (1a–c) with calix-4-arene system. Purity of all the synthesized products was ascertained on the basis of their column chromatographic resolution on silica gel using chloroform–ethylacetate (7:3, v/v) as eluent and recrystallization from a mixture of chloroform–methanol (1:1, v/v).

SYNTHESIS OF 25,26,27-TRIS(ETHOXYCARBONYLMETHOXY)- 28-(SUBSTITUTED OXY-CARBONYLMETHOXY) CALIX-4-ARENE: FIRST EXAMPLE OF CALIX-IMIDAZOLE/BENZIMIDAZOLE ANALOG

ABSTRACT Synthesis of calyx-imidazole/benzimidazole analog i.e., 25,26, 27-tris(ethoxycarbonylmethoxy)-28-({2′-phenylcarbamoyl} benzimidazolyloxycarbonylmethoxy) calyx-4-arene. 6a, 25,26, 27-tris(ethoxycarbonylmethoxy)-28-({2″-phenylcarbamoyl} 4′,5′-dihydroimidazolyloxycarbonylmethoxy) calyx-4-arene. 6b and 25,26,27-tris-(ethoxycarbonylmethoxy)-28-({2″-phenyl} aminocarbamoyl-4′,5′-dihydroimidazolyloxycarbonylmethoxy) calyx-4-arene. 6c have been described. Structure elucidation explains the interaction of substituted imidazole/benzimidazole (1a–c) with calyx-4-arene system. Purity of all the synthesized products was ascertained on the basis of their column chromatographic resolution on silica gel using chloroform–ethylacetate (7 : 3, v/v) as eluent and recrystallization from a mixture of chloroform–methanol (1 : 1, v/v).

Vapor heat capacities of some polar–polar binary systems

The calorimetric results of isobaric vapor heat capacities are presented by using a constant-flow calorimeter for five polar–polar binary systems, acetone–butanone and chloroform–ethyl acetate at 402.2 K, ethanol–methanol, ethanol– n-propanol and ethanol– n-butanol at 402.2 and 441.3 K, with respect to compositions at atmospheric pressure. The residual heat capacities and the excess heat capacities of the mixtures are calculated. Relatively significant values of the residual heat capacity are observed even at atmospheric pressure in these polar–polar binary systems. The excess vapor heat capacities of acetone–butanone system are nearly zero, but those of other polar–polar systems have relatively large positive values. These results are discussed under the consideration of the changes of the intermolecular forces. Furthermore, two well-known generalized equations of state are chosen for the estimation of the vapor heat capacities of these binary mixtures. Comparison between the calculated and the experimental results indicates that the two equations of state may be used to the vapor heat capacity estimation near atmospheric pressure even for polar systems.

Changes in Propofol Concentration in a Propofol-Lidocaine 9:1 Volume Mixture

Changes in Propofol Concentration in a Propofol-Lidocaine 9:1 Volume Mixture

Changes in propofol concentration in a propofol-lidocaine 9:1 volume mixture.

Changes in propofol concentration in a propofol-lidocaine 9:1 volume mixture.

HPTLC determination of ketorolac tromethamine

A High Performance Thin Layer Chromatography (HPTLC) method for quantification of ketorolac tromethamine, a non-narcotic and non-steroidal agent was developed. The mobile phase composition was chloroform–ethyl acetate–glacial acetic acid (3:8:0.1, v/v/v). Spectrodensitometric analysis of ketorolac tromethamine was carried out at 323 nm. The calibration curve was linear in the range of 200–700 ng. The mean values of slope, intercept and correlation coefficient were, 2941, 749583, 0.99. The method was validated for method precision, system precision, marketed sample analysis and recovery studies. The % CV for method precision studies was 1.98 ( n=6) and system precision study was 1.83 ( n=6). The average recovery was found to be 99.2%. Acid and base degraded products were adequately separated from the drug. The method was successfully used for the determination of drug from saliva. The results indicate that the method is simple, specific, selective and reliable for quantitative analysis of ketorolac tromethamine as bulk drug and from formulations. It can also be applied for the stability study of the drug and analysis of drug in biological fluids.

Sensitive determination of methomyl in blood using gas chromatography–mass spectrometry as its oxime tert.-butyldimethylsilyl derivative

A sensitive, selective and reliable method was developed to determine methomyl {methyl- N-[(methylcarbamoyl)oxy]thioacetimidate}, a carbamate insecticide in human blood, using gas chromatography–mass spectrometry. Dimethylglyoxime served as an internal standard (I.S.). Methomyl in the blood was converted to its oxime form by sodium hydroxide. The solution made acidic with hydrochloric acid was poured into a column packed with Extrelut. Methomyloxime and I.S. were eluted from the column with a mixture of dichloromethane–ethyl acetate–chloroform (65:25:10), transformed to tert.-butyldimethylsilyl derivatives, and analyzed by gas chromatography–mass spectrometry in the electron impact mode. The calibration curves were linear in the concentration range from 1 ng/g to 100 ng/g and 100 ng/g to at least 5000 ng/g. The lower limit of detection was 0.5 ng/g. The absolute recoveries were 72–93% and within-day coefficients of variation were 3.1–5.6% at blood concentrations of 10 and 1000 ng/g. Two practical forensic applications are described.

Behavioral and Chemical Defenses of Marine Prosobranch Gastropod Calliostoma canaliculatum in Response to Sympatric Seastars

The gastropod Calliostoma canaliculatum displays a series of aggressive escape behaviors upon contact with tube feet of the predatory seastars Pycnopodia helianthoides and Pisaster giganteus. Escape behaviors are predator specific. Calliostoma canaliculatum moves away from contact with P. giganteus more frequently than P. helianthoides, clamping down with the foot or retracting the head and foot into the shell when exposed to P. helianthoides. If escape from the grasp of either seastar fails, C. canaliculatum releases a yellow-colored exudate from the hypobranchial gland and subsequently retracts both the head and foot fully into the shell. This exudate contains noxious compound(s) as evidenced by retraction of tube feet and arms away from the exudate in both seastars. Tube-foot retraction responses to dilutions of the exudate indicates that both species of seastars are able to detect the exudate at a concentration of 3.2 × 10−3 mg exudate/ml seawater. Pisaster giganteus is more responsive to the exudate than Pycnopodia helianthoides, moving away from the source as well as retracting the tube feet and arm. Snails spread the exudate over their shells with their foot, perhaps to ensure defense from predators for some time period after exudate release. The exudate was collected and extracted in chloroform–ethyl acetate (1:1), then fractionated using flash chromatography. The most bioactive fraction, as evidenced by tube-foot retraction, was soluble in ethyl acetate and appeared to contain two major compounds.

Quantitation of propofol in whole blood by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric assay, using selected-ion monitoring (GC-MS-SIM) with thymol as internal standard, was developed for quantitating propofol, an intravenous anaesthetic. The method described is rapid and sensitive for the determination of propofol in whole blood. The sensitivity of the present method is 10 ng/ml. The recovery of propofol added to human whole blood in the concentration range 10-10,000 ng/ml ranged between 95 and 100%. A single extraction procedure was used with chloroform-ethyl acetate. The assay allowed the detection of two metabolites formed during propofol metabolism: 2,6-diisopropyl-1,4-quinone and 2,6-diisopropyl-1,4-quinol.

Measurement of 4-hydroxycyclophosphamide in serum by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method was developed for the measurement of 4-hydroxycyclophosphamide (4-OH-CP) in human serum, since no such assay has been described to date. In the present procedure, the serum sample was treated with semicarbazide at pH 7.4 to derivatize the 4-OH-CP to its aldophosphamide semicarbazone form. Derivatization was performed at 60 degrees C for 60 min and the product was extracted with ethyl acetate-chloroform (75:25, v/v). The derivatives formed were chromatographed on a C8 reversed-phase column with a mobile phase of 0.025 M phosphate buffer-acetonitrile (18:82, v/v) and a detection wavelength of 230 nm. The limit of detection of the assay was 0.025 mg/l for 1 ml of serum with a signal-to-noise ratio of 2. The between-assay coefficients of variation at concentrations of 0.2 and 0.4 mg/l were 7.7 and 7.0% respectively. The simplicity and specificity of this method make it directly applicable to clinical studies on 4-OH-CP pharmacokinetics.

Identification and Quantitation of Corticosteroids and Their Esters in Pharmaceutical Preparations of Creams and Ointments by Thin-Layer Chromatography and Densitometry

Abstract A rapid, simple, and specific thin-layer chromatographic (TLC) method is described for estimation of various corticosteroids and their esters when present in combination with other drugs in pharmaceutical preparation of creams and ointments. The cream or ointment is dissolved in chloroform; water and insoluble material, if any, are removed by centrifugation, and the steroid is separated from other ingredients by TLC on silica gel G with n-hexane as the first developing solvent (to wash out cream or ointment base) and chloroform–ethyl acetate (1 + 1 , v/v, for free steroids or 2 + 1 , v/v, for steroid esters) as the second developing solvent. The separated steroid or ester is visualized under shortwave UV (254 nm) and estimated by spectrodensitometry at 240 nm. Recoveries of the steroids are between 98.0 and 101.7%. Results were compared with those obtained by official methods, where applicable, and excellent agreement was found.

Extraction and high-performance liquid chromatographic methods for the γ-lactones parthenolide ( Chrysanthemum parthenium Bernh.), marrubiin ( Marrubium vulgare L.) and artemisinin ( Artemisia annua L.)

A low-pressure liquid chromatographic method using silica gel 60 with hexane—chloroform—ethyl acetate proportions varying from 80:20:0 to 80:20:6 (v/v/v) as eluent is described as a simple and inexpensive process for the isolation of the γ-lactones parthenolide, marrubiin and artemisinin from the aerial parts of feverfew, white horehound and quinghao, respectively. A selective high-performance liquid chromatographic (HPLC) method using a Superspher Si 60 column with hexane—dioxane (85:15, v/v) for elution of parthenolide and marrubiin and (90:10, v/v) for artemisinin and UV detection at 210 nm for parthenolide and artemisinin and 225 nm for marrubiin is described that allows the determination of these γ-lactones in plants. Compared with the HPLC method, the extraction yield of the large-scale process was calculated to be 72.3, 78.4 and 74.1% of the total amount of parthenolide, marrubiin and artemisinin, respectively, contained in each plant.

Measurement of carbamazepine and its main biotransformation products in plasma by HPLC.

We present a method that permits the simultaneous analysis of carbamazepine (CBZ) and its major biotransformation products, carbamazepine-10,11-epoxide (CBZ-E) and carbamazepine-10,11-dihydroxide (CBZ-diOH), in plasma samples. The method consists of plasma extraction in alkaline medium with NaCl added using chloroform-ethyl acetate (1:1, v/v) and later purification with n-hexane. The samples were submitted to reversed-phase chromatography (RP-18) using acetonitrile-water (3:7, v/v) as the mobile phase and detection at 220 nm. Recoveries of 62.0, 99.9, and 105.4% were obtained for CBZ-diOH, CBZ-E, and CBZ, respectively, with sensitivities of 0.32 micrograms/mL for CBZ-E and CBZ-dOH and of 0.64 micrograms/mL for CBZ. The method proved to be specific, thus permitting measurements in situations of drug combinations.

The Use Of Copper-(II) Bromide and N-Bromosuccinimide in the Bromination of 1-(1-Methyl-1H-pyrrol-2-yl)2-phenylethanone

Abstract Bromination of 1-(1-methyl-1H-pyrro]-2-yl)-2-phenylethanone with 1 mole of copper-(II) bromide in chloroform-ethyl acetate 1:1 mixture results in the regiospecific formation of 2-bromo-1-(1-methyl-1H-pyrrol-2-yl)-2-phenylethanone. Similar reaction with 1 mole of N-bromosuccinimide leads to α- and β-monosubstitution at pyrrole ring without affect the methylene group.

Synthetic and Structural Studies of Binuclear Organopalladium(II) Complexes Including a Bis(pyridin-2-yl)phenylmethyl Complex With Four- and Eight-Membered Palladocycle Rings, trans(N,N)-(Pd(μ-Py2PhC-N,N',C')Cl)2.½CH2Cl2.½Me2CO

The byridin-2-yl) phenylchloromethanes PyPh2CCl and Py2PhCCl undergo oxidative addition reactions with bis ( dibenzylideneacetone )palladium(0) to form {Pd(PyPh2C) Cl }2 (1) and {Pd(Py2PhC)C}2.�2CH2Cl2.�Me2CO (2), respectively. n.m.r , studies of (1) in CDCl3 indicate presence of an equilibrium between two isomers, involving the ligand (pyridin-2-yl ) diphenylmethyl in η3-coordination, {Pd(η3-PyPh2C)(μ- Cl )}2. Complex (2) has two bis (pyridin-2-yl) phenylmethyl groups present as bridging N,C′- ligands , with the groups also N,C- bidentate to each palladium, to form a binuclear compex containing four- and eight- membered palladocycles: PdC(CN)CNPdC(CN)CNBoth palladium(II) centres in (2) have square-planar 'trans-PdCN2Cl' coordination, so that (2) may be represented as trans(N,N)-{Pd(μ- Py2PhC-N,N′, C′) Cl }2.�CH2Cl2.�Me2CO. A complex similar to (2), trans(N,N)-{Pd(μ- PyPhCH -N,C?)( γmpy ) Cl }2.CH2Cl2 (3), forms on reaction of the lithium derivative of 2-benzylpyridine, Li( PyPhCH ), with dichlorobis (4-methylpyridine)palladium(II); (3) reacts with excess 2-benzylpyridine with displacement of γmpy to form trans(N,N)-{Pd(μ- PyPhCH -N,C?)(PyPhCH2) Cl }2 (4). In developing an alternative isolation procedure for (3), involving column chromatography with 4% ethyl acetate in chloroform, the coordination complex trans- bis{1-phenyl-1-(pyridin-2-yl)prop-1-en-2-olato-O,N}palladium(II), Pd{( PyPhC )C(Me)O}2 (5), was isolated in low yield. X-Ray structural studies of (2)-(5) have been completed, with all four complexes crystallizing in the monoclinic system; (2): space group P21/c, a 9.649(6), b 21.116(9), c 18.627(7)Ǻ,β 111.42(4)°, Z 4; (3): P21/c, a 13.967(2), b 13.996(3), c 18.886(2)Ǻ, β 98.74(1)°, Z 4; (4): P21/n, a 14.274(9), b 14.584(14), c 20.97(2)Ǻ, β 109.18(5)°, Z 4; (5): P21/c, a 15.184(3), b 7.887(6), c 19.240(2)Ǻ, β 97.51(1)°, Z 4.