Methyl 2-chloropropionate Research Articles

Well‐defined poly(N,N‐dimethylacrylamide) from a fast Cu(0)‐mediated reversible‐deactivation radical polymerization in water

AbstractCopper‐catalyzed reversible deactivation radical polymerization (RDRP) of N,N‐dimethylacrylamide (DMA) has been a significant challenge, particularly in aqueous environments, such as low yields, broad molecular weight distribution (MWD), and ill‐controlled molecular weights (MWs). In this work, we report the synthesis of well‐defined poly(N,N‐dimethylacrylamide) (PDMA) via a facile Cu(0)‐mediated RDRP in water. The results show that, unlike other acrylamide monomers, for DMA with abundant tertiary amide groups, the sufficient deactivation—the key to realizing control in copper‐catalyzed RDRP—cannot be simply fulfilled by just increasing the amount of deactivator (i.e., CuII species). The enhanced deactivation must be appropriately determined by also considering and selecting other reaction parameters. It is demonstrated that the use of methyl 2‐chloropropionate (MCP) as initiator and copper(II) chloride (CuCl2) as the additional catalyst is an effective combination to simultaneously enhance the deactivation control and facilitate the chain growth in aqueous Cu(0)‐mediated RDRP of DMA. This strategy successfully achieved the fast and well‐controlled synthesis of PDMAs with high monomer conversion, narrow MWDs, and a range of predefined MWs, and the well‐controlled in situ chain extensions.

Where is the induction from? Effect of disproportionation and comproportionation in Cu(0)-mediated reversible deactivation radical polymerization

There is a controversial debate about the mechanism of reversible deactivation radical polymerization (RDRP) in the presence of Cu(0). Two mechanism models have been proposed - supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) and single-electron transfer living radical polymerization (SET-LRP), however, they are contradictory to each other, and neither of them are able to fully explain experimental phenomenon in the Cu(0)-mediated RDRP process, especially a period of slow addition i.e., induction period occurs under certain reaction conditions. In this work, the induction phenomenon and its underlying mechanism was explored and clarified by using different catalyst systems (CuI, Cu(0), Cu(0)&CuII) and different initiator systems i.e., EBriB (ethyl α-bromoisobutyrate), EBrP (ethyl 2-bromopropionate), MBrP (methyl 2-bromopropionate) and MClP (methyl 2-chloropropionate). New insights on the roles of different copper species and their mutual conversion kinetics were provided. It is proved that the appearance/absence of the induction period is due to the difference in the relative concentrations of CuI and CuII accumulated at the early stage of the reaction. Moreover, the disproportionation and comproportionation co-exist in the Cu(0)-mediated RDRP system and play an essential role in establishing the equilibrium among different copper species (Cu0, CuI and CuII) at the early reaction stage.

Chiral Discrimination Mechanisms by Silylated-Acetylated Cyclodextrins: Superficial Interactions vs. Inclusion.

Cyclodextrin derivatives constitute a powerful class of auxiliary agents for the discrimination of apolar chiral substrates. Both host-guest inclusion phenomena and interactions with the derivatizing groups located on the surface of the macrocycle could drive the enantiodiscrimination; thus, it is important to understand the role that these processes play in the rational design of new chiral selectors. The purpose of this study is to compare via nuclear magnetic resonance (NMR) spectroscopy the efficiency of silylated-acetylated α-, β-, and γ-cyclodextrins in the chiral discrimination of 1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane (compound B) and methyl 2-chloropropionate (MCP). NMR DOSY (Diffusion Ordered SpectroscopY) experiments were conducted for the determination of the bound molar fractions and the association constants, whereas ROESY (Rotating-frame Overhauser Enhancement SpectroscopY) measurements provided information on the hosts' conformation and on the interaction phenomena with the guests. Compound B, endowed with fluorinated moieties, is not deeply included due to attractive Si-F interactions occurring at the external surface of the cyclodextrins. Therefore, a low selectivity toward the size of cyclodextrin cavity is found. By contrast, enantiodiscrimination of MCP relies on the optimal fitting between the size of the guest and that of the cyclodextrin cavity.

Isobaric vapour-liquid equilibrium for systems of methyl chloroacetate, methyl dichloroacetate and methyl 2-chloropropionate at 101.33 kPa

Isobaric vapour-liquid equilibrium (VLE) data for binary systems containing methyl chloroacetate (MC) + methyl 2-chloropropionate (M2C), MC + methyl dichloroacetate (MDC), and M2C + MDC at 101.33 kPa and the saturated vapour pressure data of these components were measured by using a modified Othmer still. The VLE data showed that these binary systems were all slightly positive deviation solutions compared with the ideal system. Herington area and point tests were used to confirm the thermodynamic consistency for these binary systems, and the results showed good thermodynamic consistency. The interaction energy (Einter) between these components was calculated by molecular simulation to explain the normal boiling point and VLE behavior. The simulation results showed weak hydrogen bonds between these chlorinated esters. In addition, the binary VLE experimental data were correlated by the Wilson, NRTL, and UNIQAC models. The correlated results agreed well with the experimental values.

Investigation of microstructure in poly(methyl methacrylate) prepared via ambient temperature ARGET-ATRP: a combined approach of 1D and 2D NMR spectroscopy

This investigation reports the analysis of different microstructures present in poly(methyl methacrylate) (PMMA) using1D and 2D NMR spectroscopy. The PMMA used in this study has been prepared via activators regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP) in DMF at ambient temperature using methyl 2-chloro propionate (MCP) as initiator, CuBr2 as catalyst in combination with N, N, N´, N´´, N´´- pentamethyldiethylenetriamine (PMDETA) as ligand and ascorbic acid as reducing agent.13C NMR, which provides good information about tacticity of a polymer, has been used extensively along with 1H NMR spectroscopy to extract the information about the different microstructures present in PMMA. Heteronuclear multiple-bond correlation (HMBC), heteronuclear single-quantum coherence (HSQC), and total correlation spectroscopy (TOCSY) were also used to study the position of protons, couplings with carbon etc. in the PMMA.

Utilization of One Novel Microbial Esterase WDEst9 in the Kinetic Resolution of (S)-Methyl 2-chloropropionate and (S)-Ethyl 2-chloropropionate

One novel microbial esterase WDEst9 from Dactylosporangium aurantiacum subsp. Hamdenensis NRRL 18085 was functionally characterized and the results demonstrated that the enantio-preference of WDEst9 was oppo-site to that of three other microbial esterases(BSE01701, PHE14 and Bae02030) in the kinetic resolution of racemic methyl lactate. We further investigated the potential of esterase WDEst9 in the kinetic resolution of both (±)-methyl 2-chloropropionate and (±)-ethyl 2-chloropropionate. The enantio-preference of WDEst9 was also interestingly op-posite to that of esterases EST12-7 and EstC10, and generated (S)-methyl 2-chloropropionate and (S)-ethyl 2-chloropropionate with high enantiomeric excess(both e.e. >98%) and high yield after many iterations of process optimization. Through genome mining, microbial esterase WDEst9 was characterized to be a novel esterase which may provide valuable complementary enantio-selectivity and possesses very good potential in the kinetic resolution of high value-added chiral chemicals.

Highly-reactive haloester surface initiators for ARGET ATRP readily prepared by radio frequency glow discharge plasma.

New surface initiators for ARGET ATRP (activators regenerated by electron transfer atomic transfer radical polymerization) have been prepared by the plasma deposition of haloester monomers. Specifically, methyl 3-bromopropionate (M3BP), methyl 2-chloropropionate, and ethyl 2-fluoropropionate (E2FP) were plasma deposited onto glass discs using RF glow discharge plasma. This technique creates surface coatings that are resistant to delamination and rich in halogen species making them good candidates for surface initiators for ARGET ATRP. Of all the plasma polymerized surface coatings, M3BP showed the highest halogen content and was able to grow 2-hydroxyethyl methacrylate (HEMA) polymer brushes on its surface via ARGET ATRP in as little as 15 min as confirmed by XPS. Surprisingly, E2FP, a fluoroester, was also able to grow HEMA polymer brushes despite fluorine being a poor leaving group for ARGET ATRP. The versatility of RF glow discharge plasma offers a clear advantage over other techniques previously used to immobilize ARGET ATRP surface initiators.

Characterization of a novel deep-sea microbial esterase EstC10 and its use in the generation of (R)-methyl2-chloropropionate

A novel esterase EstC10 from Bacillus sp. CX01 isolated from the deep sea of the Western Pacific Ocean and the functionalities of EstC10 was characterized. At present, the reports about the kinetic resolution of racemic methyl 2-chloropropionate were quite rare. So we developed deep-sea microbial esterase EstC10 as a novel biocatalyst in the kinetic resolution of racemic methyl 2-chloropropionate and generate (R)-methyl 2-chloropropionate with high enantiomeric excess (>99%) after the optimization of process parameters such as pH, temperature, organic co-solvents, surfactants, substrate concentration and reaction time. Notably, the optimal substrate concentration (80 mmol/L) of esterase EstC10 was higher than the kinetic resolution of another esterase, Est12-7 (50 mmol/L). The novel microbial esterase EstC10 identified from the deep sea was a promising green biocatalyst in the generation of (R)-methyl 2-chloropropionate as well of many other valuable chiral chemicals in industry.

Accuracy of reduced mobilities and measurement of instrumental parameters in ion mobility spectrometry

Ion mobility spectrometry (IMS) separates gas-phase ions drifting under an electric field according to their size to charge ratio. We used electrospray ionization-drift tube IMS coupled to quadrupole mass spectrometry to obtain the mobilities of common amino acids, amines, valinol, atenolol, and the chemical standards tetramethylammonium ion (TMA), tetraethylammonium ion (TEA), tetrapropylammonium ion (TPA), and tetrabutylammonium (TBA) ions, 2,4-lutidine and 2,6-di-tert-butyl pyridine (DTBP). The mobilities were obtained in pure nitrogen or when shift reagents (SR) such as ammonia, 2-butanol, ethyl lactate, methanol, methyl 2-chloropropionate, nitrobenzene, 1-phenyl ethanol, trifluoromethyl benzyl alcohol, and water were introduced in the buffer gas. We found important differences in the buffer gas temperature between different regions of the drift tube and differences between the buffer gas and drift tube temperatures, which is normally used instead of the buffer gas temperature in reduced mobility calculations. Therefore, we used the buffer gas temperature instead of the drift tube temperature and a calibration method with two types of chemical standards, finding excellent precision, reproducibilities from 0.3 to 0.6% for reduced mobilities (K0) of the chemical standards during nine months. Repeatability during this period was 0.17% for the drift times of all the analytes. We also show that the changes in instrumental parameters such as temperature, pressure and voltage that produce important variations in drift times are small; for this, we recommend to calculate K0 from calibration with chemical standards instead of replacing instrumental parameters in the IMS fundamental equations.

Functional Characterization of a Novel Marine Microbial Esterase and its Utilization in the Enantioselective Preparation of (R)-Methyl 2-Chloropropionate.

Chiral 2-chloropropanoic acids and their ester derivatives are crucial intermediates in the synthesis of many chemicals, especially herbicides. The enzymatic synthesis of chiral 2-chloropropanoic acids and their ester derivatives by esterases was not easily achieved, because the structural difference between the two enantiomers was too small to be recognized by esterases. Herein, we report the expression and functional characterization of one novel low temperature-resistant esterase EST12-7 identified from the genome of Pseudonocardia antitumoralis SCSIO 01299 isolated from the sediments of the South China Sea. Biocatalyst EST12-7 could hydrolyze racemic methyl 2-chloropropinate and generate optically pure (R)-methyl 2-chloropropinate with high enantiomeric excess (>99%) and conversion (>49%) after process optimization. Notably, the addition of different surfactants and using surfactants of different concentrations in the kinetic resolution catalyzed by EST12-7 could greatly affect the enantiomeric excess and conversion rate of product (R)-methyl 2-chloropropinate.

Control of stereochemistry in atom transfer radical addition and step-growth radical polymerization by chiral transition metal catalysts

A series of chiral transition metal catalysts of ruthenium(II), iron(II), copper(I), and rhodium(I) were used to control the stereochemistry in the step-growth radical polymerization of 3-butenyl 2-chloropropionate (BCP) with both unconjugated CC and reactive C–Cl bonds in a single molecule and atom transfer radical addition (ATRA) as a model reaction for the polymerization. Among the various metal catalysts with chiral ligands, Ru2Cl4[(−)-DIOP]3 [DIOP=2,3-(isopropylidenedioxy)-2,3-dihydroxy-1,4-bis(diphenylphosphanyl)butane] induced asymmetric ATRA with 10% ee between CCl4 and 3-butenyl acetate (BAc), which has an unconjugated CC bond as a model olefin of the monomer. However, this ruthenium catalyst was not sufficiently active to induce ATRA between the C–Cl bond in methyl 2-chloropropionate (MCP), which is a model chloride for the monomer, and the CC bond in BAc, as well as the step-growth radical polymerization of BCP. Whereas chiral iron and copper catalysts, such as FeCl2/(−)-DIOP and CuCl/(−)-sparteine, efficiently allowed the ATRAs and the step-growth radical polymerization to result in the desired 1:1 adducts and oligomers, respectively, almost no optical activity was observed for the products. However, the diastereoselectivity was changed in both the ATRA and the polymerization by the metal catalysts with chiral or achiral ligands.

Mobilities of amino acid adducts with modifiers in the buffer gas of an ion mobility spectrometer depended on modifier size and modifier–amino acid interaction energy

Buffer gas modifiers have been used to separate overlapping analytes in ion mobility spectrometry (IMS); separation relies on the formation of large and slow modifier–analyte adducts with different mobilities; however, it is unknown the cause of separation and predictions about a given separation cannot be made. Therefore, we vaporized phenylethanol modifier (P) into the buffer gas of an ion mobility spectrometer coupled to a quadrupole mass spectrometer to explain the selective effect of this modifier on the mobilities of asparagine, methionine, and phenylalanine amino acids; amino acid mobilities decreased selectively due to formation of slow phenylethanol:amino acid ion adducts. Mobility reductions were asparagine (−19.4%), methionine (−19.5%), and phenylalanine (−20.8%). Then, we compared phenylalanine and methionine mobility reductions when 2-butanol (B), methyl 2-chloropropionate (M), and α-(trifluoromethyl)benzyl alcohol (F) modifiers were introduced in the buffer gas; mobility reductions were M>P>F>B for both amino acids. Parameters such as modifier size, modifier–ion interaction energies, modifier proton affinities, steric and inductive effects, and intramolecular hydrogen bond strength explained modifier effect on mobility reduction. High modifier–ion interaction energies increase adduct average lifetimes and large modifiers produce adducts with large collision cross sections and explain mobility differences between adducts. The other parameters are taken into account when calculating modifier–ion interaction energies.

Synergistic effects of trace amounts of water in the enantiodiscrimination processes by lipodex E: a spectroscopic and computational investigation.

Nuclear magnetic resonance (NMR) investigations on mixtures containing octakis(3-O-butanoyl-2,6-di-O-pentyl)-γ-cyclodextrin (Lipodex E) and each enantiomer of methyl-2-chloropropionate (MCP) ascertained the role of trace amounts of water in the enantiodiscrimination processes. Water is deeply included into the cyclodextrin and favors the formation of the inclusion complex with (S)-MCP, whereas (R)-MCP is only slightly affected, thus causing a significant increase of NMR differentiation. Molecular dynamics simulations were performed to shed light on the possible behavior of Lipodex E in different conditions (i.e., solvent, inclusion complexes), providing energetic and atomistic details that are in agreement with NMR observations.

Enantioseparation of Methyl 2-Hydroxypropionate with Two Peracylated β-Cyclodextrin Derivatives as CGC Chiral Stationary Phases

Two peracylated β-cyclodextrin derivatives, 2,3,6-tri-O-valeryl-β-cyclodextrin and 2,3,6-tri-O-octanoyl-β-cyclodextrin, were synthesized and used as capillary gas chromatography (CGC) chiral stationary phases. The two peracylated β-cyclodextrin derivatives showed enantioseparation abilities to some chiral compounds tested, such as enantiomers of methyl 2-chloropropionate, 5-hydroxy-4, 4-dimethyl-dihydrofuran-2-one, and methyl 2-hydroxypropionate. As CGC chiral stationary phases, the two peracylated β-cyclodextrin derivatives showed excellent enantioseparation abilities to methyl 2-hydroxypropionate (i.e., methyl lactate). On 2,3,6-tri-O-valeryl-β-cyclodextrin, the enantiomer separation factor and resolution of methyl lactate were 1.21 and 6.08, respectively, and on 2,3,6-tri-O-octanoyl-β-cyclodextrin, 1.22 and 5.49, respectively. The enantioseparation results of methyl lactate on the two peracylated β-cyclodextrin derivatives were better than on most reported β-cyclodextrin derivatives, including a commercial chiral column of permethylated β-cyclodextrin tested in this study. Results suggest that CGC methods using 2,3,6-tri-O-valeryl-β-cyclodextrin or 2,3,6-tri-O-octanoyl-β-cyclodextrin as chiral stationary phase could be used for enantioseparation and evaluating the enantiomeric optical purity of methyl lactate.

SET-LRP of N-(2-hydroxypropyl)methacrylamide in H2O

Cu(0) wire-catalyzed SET-LRP of N-(2-hydroxypropyl)methacrylamide (HPMA) initiated with methyl 2-chloropropionate (MCP) in H2O at 50 °C exhibited linear kinetics up to 90% conversion using 0.5 equivalents of Me6-TREN with respect to initiator concentration.

Acrylamide Homopolymers and Acrylamide–N-Isopropylacrylamide Block Copolymers by Atomic Transfer Radical Polymerization in Water

Atomic transfer radical polymerization (ATRP) of acrylamide has been accomplished in aqueous media at room temperature. By using methyl 2-chloropropionate (MeClPr) as the initiator and tris[2-(dimethylamino)ethyl]amine (Me6TREN)/copper halogenide (CuX) as the catalyst system, different linear polyacrylamides with apparent molecular weights up to >150 000 g/mol were synthesized with dispersities as low as 1.39. The molecular weights agreed well with the theoretical ones at relatively low-medium monomer/initiator ratios (<700:1). Initial chain extension experiments (isolated macroinitiator) resulted in a polymer with bimodal distribution. However, in situ chain extension experiments, carried out by addition of a second fresh batch of monomer to the reaction mixture, confirmed the living nature of the polymerization. By adding a fresh batch of monomer to a linear macroinitiator (Mn = 22 780 g/mol, PDI = 1.42) in solution, an increase in the molecular weight up to 30 220 g/mol (PDI = 1.64) was observed. In addition, linear polyacrylamides were used as macroinitiators for the synthesis of block copolymers polyacrylamide-b-poly(N-isopropylacrylamide).

Controlled Radical Polymerization of Vinyl Acetate with Cyclopentadienyl Chromium β-Diketiminate Complexes: ATRP vs OMRP

The ability of compounds CpCrII(nacnacAr,Ar) (Ar = Dipp, 1; Xyl, 2) to catalyze the atom transfer radical polymerization (ATRP) of vinyl acetate has been explored using methyl 2-chloropropionate as initiator. Polymerizations were also carried out under reverse ATRP conditions with thermal initiation by 2,2′-azobis(4-methoxy2,4-dimethylvaleronitrile) (V-70) in the presence of compounds CpCrIII(nacnacAr,Ar)Cl (Ar = Dipp, 3; Xyl, 4). All data suggest that these processes are in fact proceeding by organometallic-mediated radical polymerization (OMRP). Stoichiometric reactions between complex 2 and the chlorinated compounds CH3CH(Cl)COOCH3, ClCH2COPh, CH3CHClOOCCH3, ClCH2OOCtBu, and ClCH2tBu in the absence of monomer aid in the interpretation of the polymerization results. The first two substrates show rapid one-electron oxidative additions to generate 4 and O-bonded CrIII products, whereas the third and fourth substrates add much more slowly to generate 4 and C-bonded CrIII products; ClCH2tBu does not react. ...

Solvent effects on polymerization of functionalized monomers in presence of alkyl halide/CuBr without a ligand

A modified system of atom transfer radical polymerization was used to perform polymerization of sodium o-methacryloylaminophenylarsonate (o-MAPHA-Na). The reaction was carried out without ligand at 48 °C for 45 h with methyl 2-chloro-propionate (MCP) as the initiator, copper bromide (CuBr) as the metal, and different mixtures of polar solvents, including: dimethylformamide (DMF):H2O (60:40), dimethylsulfoxide (DMSO):H2O (20:80), and DMSO. The 1H NMR spectra showed that MCP was covalently attached as end group of the resulting polymers. Unexpectedly, we found that o- and p-MAPHA-Na could polymerize in the presence of alkyl halides without any initiation method to produce free radicals from alkyl halide. Further experiments suggested that radicals could be generated from the used monomer by initiation methods such ultraviolet radiation of environmental light or temperature. Thus, it was possible that the monomer generated phenyl radicals by breaking its C-As bond. Reactions of o-MAPHA-Na and o-MAPHA with MCP and different ratios of H2O:DMF and H2O:Metanol (MeOH) showed that water was necessary for polymerization to proceed. Finally, we found that o-MAPHA underwent self-initiated polymerization when water was present in the reaction media.

Chromatographic Properties of 2,3-Di-O-allyl-6-O-acyl-β-cyclodextrins as Chiral Stationary Phases of Capillary GC

Three 2,3-di-O-allyl-6-O-acyl-β-cyclodextrins, 2,3-di-O-allyl-6-O-valeryl-β-cyclodextrin, 2,3-di-O-allyl-6-O-heptanoyl-β-cyclodextrin, and 2,3-di-O-allyl-6-O-octanoyl-β-cyclodextrin, were synthesized and their chromatographic properties were investigated. 2,3-di-O-allyl-6-O-acyl-β-cyclodextrins cannot only separate the enantiomers of methyl 2-chloropropionate, methyl 2-bromopropionate, methyl 2-hydroxypropionate, allethrone acetate, propargyllone acetate, and 1-(2,4-dichlorophenyl)ethanol, but also possess enantiomer separation abilities to some enantiomers of pyrethroic acid methyl esters and epoxides. The enantiomer separation results on the three 2,3-di-O-allyl-6-O-acyl-β-CDs were used to draw some empirical rules about enantiomer separation together with the enantiomer separation results on other CDs. Acyl groups on CDs, especially 3-position acyl groups on CDs, are favorable for the enantiomer separation of pyrethroic acid methyl esters, while acyl groups on 6-position of CDs are beneficial for the enantiomer separation of epoxides, but allyl on CDs are less favorable for enantiomer separation than pentyl. The empirical rules summarized here have some practice significances in selecting CGC chiral stationary phase for solving enantiomer separation problems. Also, the three 2,3-di-O-allyl-6-O-acyl-β-CDs may be used in practical chiral analysis.

Alkyl chloride initiators for SET‐LRP of methyl acrylate

AbstractSingle‐electron transfer living radical polymerization (SET‐LRP) proceeds by an outer‐sphere single‐electron transfer mechanism that induces a heterolytic bond cleavage of the initiating and propagating R‐X (where X = Cl, Br, and I) species. Therefore, unlike the homolytic bond cleavage mechanism claimed for ATRP, SET‐LRP is expected to show a small dependence of the nature of the halide group on the apparent rate constant of activation. This means the R‐X with X = Cl, Br, and I must all be efficient initiators for SET‐LRP and no chain transfer must be observed in the case of initiators with X = Br and I. Here, we report the SET‐LRP of methyl acrylate initiated with the alkyl chlorides methyl‐2‐chloropropionate (MCP) and chloroform (CHCl3) and catalyzed by Cu(0)/Me6‐TREN/CuCl2 in DMSO at 25 °C. A combination of kinetic and structural analysis was used to elucidate the MCP and CHCl3 initiating behavior under SET‐LRP conditions, and to demonstrate the very small dependence of the SET‐LRP apparent rate constant of propagation on X while providing polymers with well defined architecture. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4917–4926, 2008