Methyl 2-chloropropionate Research Articles

Controllable synthesis of poly( N-vinylpyrrolidone) and its block copolymers by atom transfer radical polymerization

At room temperature atom transfer radical polymerization (ATRP) of N-vinylpyrrolidone (NVP) was carried out using 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetra-azacyclo-tetradecane (Me 6Cyclam) as ligand in 1,4-dioxane/isopropanol mixture. Methyl 2-chloropropionate (MCP) and copper(I) chloride were used as initiator and catalyst, respectively. The polymerization of NVP via ATRP could be mediated by the addition of CuCl 2. The resultant poly( N-vinylpyrrolidone) (PNVP) has high conversion of up to 65% in 3 h, a controlled molecular weight close to the theoretical values and narrow molecular weight distribution between 1.2 and 1.3. The living nature of the ATRP for NVP was confirmed by the experiments of PNVP chain extension. With PNVP–Cl as macroinitiator and N-methacryloyl- N′-(α-naphthyl)thiourea (MANTU) as a hydrophobic monomer, novel fluorescent amphiphilic copolymers poly( N-vinylpyrrolidone)- b-poly( N-methacryloyl- N′-(α-naphthyl)thiourea) (PNVP- b-PMANTU) were synthesized by ATRP. PNVP- b-PMANTU copolymers were characterized by 1H NMR, GPC-MALLS and fluorescence measurements. The results revealed that PNVP- b-PMANTU presented a blocky architecture.

Probing the Influence of Polymer Architecture on Liquid−Liquid Phase Transitions of Aqueous Poly(N,N-dimethylacrylamide) Copolymer Solutions

Thermosensitive poly(N,N-dimethylacrylamide-co-N-phenylacrylamide) (DMA-co-PhAm) copolymers were prepared by atom transfer radical polymerization (ATRP) in methanol/water mixtures at room temperature with methyl 2-chloropropionate as the initiator and CuCl/Me6TREN as the catalyst. The resultant DMA-co-PhAm copolymers had tailored compositions and controlled molecular weights, and their aqueous solutions underwent liquid−liquid phase separation upon heating. These phase transition temperatures, measured by the cloud point method, were dependent on polymer concentrations, compositions, and molecular weights. The efficiency of the thermally induced liquid−liquid phase transition, i.e., the yield of phase-separated polymer, increased with increasing solution temperature, suggesting this thermally induced liquid−liquid phase transition to be a continuous equilibrium process. The efficiency of phase separation could be enhanced by adding NaCl to the solution.

Mapping the substrate selectivity and enantioselectivity of esterases from thermophiles

To identify potential applications of nineteen esterases from thermophiles, we mapped their substrate selectivity and enantioselectivity using a library of 50 esters. We measured the selectivities colorimetrically using Quick E, which uses pH indicators to detect hydrolysis and a chromogenic reference compound as an internal control. The substrate selectivity mapping revealed one esterase, E018b, with a strong preference for acetyl esters (14- to 25-fold over hexanoate). The enantioselectivity mapping revealed a number of cases of high enantioselectivity. Thirteen of the 19 esterases showed moderate or better enantioselectivity (>19) toward 1-phenethyl butyrate favoring the ( R)-enantiomer and two esterases (E008, E013) showed moderate or better enantioselectivity (>20) toward methyl 2-chloropropionate favoring the ( S)-enantiomer. Three esterases (E001, E004, E005) showed high (>46) enantioselectivity toward menthyl acetate favoring the ( R)-enantiomer. This rapid mapping of the selectivity simplifies the characterization of new enzymes.

Reactions of Nitroarenes with Secondary and Tertiary Carbanions Bearing Both a Leaving Group and Electron‐Withdrawing Group: An Approach to Dihydronaphth[2,1‐c]isoxazole N‐Oxides and Dihydroisoxazolo[4,3‐f]quinoline N‐Oxides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reactions of nitroarenes with secondary and tertiary carbanions bearing both a leaving group and electron‐withdrawing group: An approach to dihydronaphth[2,1‐c]isoxazole N‐oxides and dihydroisoxazolo[4,3‐f]quinoline N‐oxides

Abstract2‐Nitronaphthalene (1) and 6‐nitroquinoline (2) underwent direct cyclocondensation with secondary and tertiary carbanions derived from a methylene and methine group bearing both a leaving group and electron‐withdrawing group (e.g., methyl chloroacetate, ethyl chloroacetate, chloroacetonitrile, methyl 2‐chloropropionate, ethyl 2‐chloropropionate and 2‐chloropropionitrile) in the sodium hydride/N,N‐dimethylformamide system at low temperature, giving the corresponding dihydronaphth[2,1‐c]isoxazole N‐oxides 3 and dihy‐droisoxazolo[4,3‐f]quinoline N‐oxides 4. On the other hand, nitroarenes 1 and 2 reacted with secondary carbanions in the sodium hydride/tetrahydrofuran system to yield the corresponding conventional vicarious nucleophilic substitution (VNS) products 5 and 6.

Synthesis of Some New Tricyclic 1,4‐Benzothiazinones

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselectivity of Candida rugosa lipase in the hydrolysis of 2-chloropropionic acid methyl ester

The enantioselectivity of lipase from Candida rugosa in the hydrolysis of methyl 2-chloropropionate was measured at several substrate concentrations. Initial reaction rates for the pure enantiomers differ by a factor of 2.1 (low substrate concentration) and 1.6 (high substrate concentration), respectively. Determination of the enantiomeric ratio, E-value, in (1) kinetic resolution experiments, and (2) by the method of initial reaction rates on mixed enantiomers, however, showed E=1 (no enantioselectivity) for the full range of substrate concentrations.

Optical methyl 2-chloropropionate synthesis by decomposition of methyl 2-(chlorocarbonyloxy)propionate with hexaalkylguanidinium chloride hydrochloride

The decomposition of methyl S-(−)-2-(chlorocarbonyloxy)propionate in the presence of hexaalkylguanidinium chloride hydrochloride was confirmed to correspond to a nucleophilic substitution of the second order. However, racemization occured by the contact between the catalyst and methyl R-(+)-2-chloropropionate ( I ). This phenomenon is caused by the exchange between the chloride ion from catalyst and the chlorine atom of ( I ) according to a SN 2 mechanism as well.

Synthesis of some new tricyclic 1,4-benzothiazinones

2-Aminothiophenol on reaction with dimethyl oxalate and methyl 2-chloropropionate gives 1,4-benzothiazinone (la, 1b) which when reacted with ethyl chloroacetate give N-ethoxycarbonylmethyl-1,4-benzothiazine-2,3-diene (2a 1 ). Compound 2 on reaction with hydrazine hydrate affords N-hydrazidomethyl-1,4-benzothiazine-2,3-dione (3). Compound 3 is cyclized in presence of ammonium acetate and acetic acid to give 5-methyl[1,2,4]triazino-6-oxo[3,4-c]-3(1H)-[1,4]benzothiazine (4b 1 ). Compound 1 on reaction with phosphorus oxychloride gives 3-chloro-1,4-benzothiazine-3-one (5a) which when reacts with ammonium sulfocyanide affords 1,4-benzothiazin-2-one-3-ylisocyanate (6a). Compound 6 when reacted with methyl cyanide gives the desired tricyclic compound 2-thio-6-methyl[1,3,5]triazolo[3,4-c]benzothiazine-2-one (7a).

Quantitative analysis of enantioselective enzymatic hydrolysis with non-enantioselective removal of chiral products

Kinetic resolution of racemic compounds by enzymatic hydrolysis with non-enantioselective separation of enantiomer products via a separator or ion-pair formation has been quantitatively analyzed. Theoretical results indicate that the removal of chiral products has profound effects on improving the conversion and enantiomeric excess for the desired chiral substrate or product. The analysis was confirmed from lipase-catalyzed hydrolysis of racemic methyl 2-chloropropionate in the presence of pyrrolidine in buffer saturated dichloromethane.

Hydrogen Stretching Vibrational Circular Dichroism in Methyl Lactate and Related Molecules

The CH- and OH-stretching vibrational circular dichroism (VCD) spectra of methyl lactate and related molecules in CCl4 solution have been investigated to identify solution conformations and establish a correlation between OH- and methine-stretching VCD intensity and molecular structure. Deuterium substitution was used when possible to remove overlapping absorption features in the CH-stretching region. Anisotropy ratios between +2.1 × 10-4 and +2.8 × 10-4 were measured for the methine-stretching VCD of the molecules with both α-oxy and α-CO substituents: (S)-methyl-d3 lactate, (S)-methyl-d3 2-(methoxy-d3)-propionate, di(methyl-d3) d-tartrate, (S)-methyl-d3 mandelate, (S)-methyl-d3 O-(acetyl-d3)-mandelate, and (S)-benzoin. The methine-stretching VCD intensity serves as a marker for both absolute configuration and solution conformation in these molecules, as previously demonstrated for amino acids and peptides. In (S)-methyl 2-chloropropionate, (R)-methyl 3-hydroxy-2-methylpropionate, and (S)-methyl 3-hydroxybutyrate, the net CH-stretching VCD intensity is small relative to that in the other molecules studied. Ab initio calculations of geometries, vibrational frequencies, and unpolarized infrared absorption (IR) and VCD intensities were carried out to identify the most abundant solution conformers from the VCD spectra and to correlate OH- and methine-stretching VCD intensity with molecular conformations. Factors leading to large methine-stretching VCD anisotropy ratios are assessed.

Chiral discrimination of inhalation anesthetics and methyl propionates by thickness shear mode resonators: new insights into the mechanisms of enantioselectivity by cyclodextrins.

The discrimination of the enantiomers of methyl lactate, methyl 2-chloropropionate, and the inhalation anesthetics enflurane, isoflurane, and desflurane in the gas phase has been performed using thickness shear mode resonators. The selective coating was a modified perpentylated gamma-cyclodextrin derivative dissolved in a polysiloxane matrix. A new model for the sorption of the chiral compounds into the cyclodextrin cavities and into the polymer matrix was established for the purpose of characterizing the sensor responses. This characterization included the fitting of the sensor responses (preferential and nonpreferential sorption) according to the model and extracting the characteristic parameters. In particular we attempted to explain the observed variation of the chiral discrimination factor alpha with changing analyte or cyclodextrin concentrations and search for an invariable parameter, characteristic for a certain analyte-cyclodextrin combination. The process of chiral or "molecular" recognition was thoroughly investigated.

Kinetic and Enantioselective Behaviour of Isoenzymes A and B from Candida Rugosa Lipase in the Hydrolysis of Lipids and Esters

The isoenzymes A and B from C. rugosa lipase have been kinetically characterized by non-linear regression methods measuring the hydrolysis of tributyrin (lipase activity), p-nitro-phenyl acetate (esterase activity) and methyl 2-chloropropionate (enantioselectivity). With tributyrin as substrate, the specificity constant (k app cat/k app m) for lipase A is about 2-fold that of the lipase B. This confirms the higher specificity of lipase A for substrates containing butyric acid moieties. However, the kinetic behaviour of both isoenzymes for the hydrolysis of p-nitrophenyl acetate is quite similar, with lipase A showing a slight preference for this substrate. Kinetic analysis with the substrates methyl (R)-(+) and methyl (S)-(-) 2-chloropropionates showed that both isoenzymes exhibit stereospecificity for the enantiomer R and display non-Michaclian kinetics of a sigmoidal type. Since this behaviour precludes the usual treatment on the basis of the enantiomeric ratio [(Vmax/Km)fast/(Vmax/Km)slow], enantioselectivity was quantified using the areas under the v-[S] curves. Thus, the ratio between the areas under the curves for the two enantiomers assayed increases from 1.27 for isoenzyme A to 1.68 for isoenzyme B. This result clearly shows that isolation and purification of isoenzymes may enhance the enantioselective properties of an enzymatic system.

Determination of the gas-liquid partition isotherms of the enantiomers of methyl 2-chloropropionate on trichloroacetyl pentyl β-cyclodextrin using the elution by characteristic points method

The gas-liquid partition isotherms of the enantiomers of methyl 2-chloropropionate on a trichloroacetyl pentyl β-cyclodextrin stationary phase were determined at three different temperatures using the elution by characteristic points method. The isotherms were described using the single-component and competitive bi-Langmuir isotherm equations. The measured and calculated isotherms as well as the retention factor and separation selectivity data agree, indicating that these isotherms might be suitable for the modeling of the preparative-scale gas chromatographic separation of the enantiomers.

Use of the equilibrium-dispersive model of nonlinear gas chromatography for the modelling of the elution band profiles in the preparative-scale gas chromatographic separation of enantiomers

The equilibrium-dispersive model of chromatography is applied to the study of enantioselective separations of methyl 2-chloropropionate in gas chromatography. The single-component and competitive bi-Langmuir isotherm equations that describe the sorption behavior of single enantiomers and racemates, respectively, are utilized by the equilibrium-dispersive model to predict the elution band profiles of single-component and binary mixture samples. The measured and the calculated band profiles are compared both for the analytical open tubular column used to acquire the isotherm data and for the 1 m×22.5 mm I.D. preparative packed column, followed by the comparison of the enantiomeric purity vs. production curves for both the measured and the simulated systems.

Preparative gas chromatographic separation of the enantiomers of methyl 2-chloropropionate using a cyclodextrin-based stationary phase

The enantiomers of methyl 2-chloropropionate, a volatile synthetic precursor, have been separated by preparative-scale gas chromatography using a 1 m × 22.5 mm I.D. column, packed with 20% (w/w) trichloroacetyl ß-cyclodextrin-coated 60–80-mesh Chromosorb A. The preparative column was installed in a custom-designed preparative gas chromatograph and operated in the isothermal mode. An effluent-sampling interface valve, located between the exit of the preparative column and the fraction collector took 10-μl samples of the effluent gas every 20 s and sent the samples onto a short, efficient analytical capillary column to provide on-line enantiomeric analysis of the eluting bands. This near-real-time knowledge of the enantiomer composition of the effluent gas leads to aggressive, yet safe, fraction pooling schemes and permits the precise calculation of product purity, recovery and production rate. Results for the preparative separation of racemic as well as enantiomerically enriched (95% enantiomeric excess) feedstock are presented in this paper.

Comparison of enzymatic kinetic resolution in a batch reactor and a CSTR

The difference between a continuous stirred-tank reactor (CSTR) and a batchwise reactor has been shown for the enzymatic kinetic resolution of enantiomers. By macroscopic reactor balancing new quantitative relationships between enzyme enantioselectivity, substrate or product enantiomeric excess, and the extent of conversion have been deduced for chiral resolution in a CSTR. They were experimentally verified for the esterase-catalyzed resolution of racemic methyl 2-chloropropionate. This reaction was performed both in a batch system and in an enzyme membrane reactor functioning as a CSTR. As expected, the batchwise reaction was superior.

Sequential Kinetic Resolution by two Enantioselective Enzymes

Enhancement of the enantioselectivity by simultaneous use of two enzymes in a sequential kinetic resolution process is presented. The model system consisted of carboxylesterase NP catalyzed hydrolysis of racemic methyl 2-chloropropionate, followed by dehalogenation of the enantiomerically enriched 2-chloropropionate by DL-dehalogenase into lactate. Optimal results are shown to be attained when the conversion rates of both faster reacting enantiomers are the same. An optimization parameter D for sequential resolutions is introduced. The kinetics of both reaction steps were investigated separately by progress curve analysis, and the enantioselectivity of the enzymes was determined. From a quantitative kinetic model we could formulate the sequential resolution, which yielded the predicted improvements of product enantiomeric excess.

Improvement of enantioselective enzymatic ester hydrolysis in organic solvents

A method is presented to improve the enzymatic enantioselective hydrolysis of chiral esters in water-saturated organic solvents. It is shown that addition of a non-reactive amine to the reaction mixture leads to the formation of an ion-pair with the produced carboxylic acid. Yield and enantiomeric excess are increased in lipase catalyzed kinetic resolutions of methyl 2-chloropropionate and glycidyl butyrate in various solvents. Chemical background hydrolysis was reduced with respect to aqueous solvents. A second phase was formed during reaction in apolar solvents, due to ion-pair formation, which may facilitate the isolation of the desired compound.

Pulse radiolysis studies on the polymerization of 1,6-hexanediol diacrylate in cyclohexane solvent

The mechanism of initiation and kinetics of radiation induced polymerization of 1,6-hexanediol diacrylate (HDDA) was studied by pulse radiolysis with optical detection in cyclohexane solution and in pure HDDA at room temperature. In both cases a transient light absorption decreasing with the wavelength in the 270–400 nm wavelength range, but possessing a shoulder at 310 nm was observed. The spectrum did not change with time after the pulse. The absorption is due to α-carboxyalkyl radicals: the assignment was supported by the results obtained from the reaction of electrons with methyl 2-chloropropionate leading to dechlorination. The radicals produced from HDDA or from the chloro compound decayed in a second order process with rate parameters of 5 · 10 8 and of 4 · 10 9 mol -1 dm 3 s -1 in cyclohexane. In the presence of oxygen the corresponding peroxy radicals decaying in very slow process (several milliseconds) were observed. The results are interrupted in terms of radical polymerization mechanism.