CN103242497A - Method for synthesising diblock copolymer by simultaneous chemoenzymatic process and one-pot process - Google Patents
Method for synthesising diblock copolymer by simultaneous chemoenzymatic process and one-pot process Download PDFInfo
- Publication number
- CN103242497A CN103242497A CN2013101557145A CN201310155714A CN103242497A CN 103242497 A CN103242497 A CN 103242497A CN 2013101557145 A CN2013101557145 A CN 2013101557145A CN 201310155714 A CN201310155714 A CN 201310155714A CN 103242497 A CN103242497 A CN 103242497A
- Authority
- CN
- China
- Prior art keywords
- reaction
- polymerization
- pot
- block copolymer
- polymerization monomer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
The invention discloses a method for synthesising a diblock copolymer by simultaneous chemoenzymatic process and one-pot process, and belongs to the technical field of synthesis and preparation for a high-molecular material. Enzymatic polymerization and atom transfer radical polymerization are fused in a reaction system, and two polymerization reactions with different polymerization mechanisms are simultaneously initiated to be simultaneously performed by the different functional groups of a bifunctional initiator in the conventional reaction conditions. With the adoption of the method disclosed by the invention, the cockamamie processes of multi-kettle polymerization and single-kettle multi-step polymerization are avoided, separation and purification for an intermediate compound needed in the multi-step operations are avoided, the pollution brought by a solvent is reduced, the supercritical CO2 reaction condition used in a chemoenzymatic and one-pot polymerization technology is avoided, and the cockamamie synthesis steps are avoided by the selected bifunctional initiator, so that the production cost is reduced; the method is efficient and energy-saving, and easier for industrial popularization; and a simpler and more convenient method is provided for synthesising a functional block polymer.
Description
Technical field
The invention belongs to the technical field of synthesis of polymer material and preparation, the method for " the chemical enzyme process simultaneously one pot synthetic " bi-block copolymer that adopts particularly that enzymatic ring-opening polymerization and atom transfer radical polymerization combine.
Background technology
Along with development of science and technology, subjects such as chemistry, bio-science, medical science, physics, information science constantly intersect infiltration, have promoted development and the application of novel material, but still can not satisfy people to the demand of functional novel material.Polymerization means such as the active free radical polymerization that adapts to this demand and grow up, ring-opening polymerization and click-reaction have caused domestic and international high molecular scholar and material scholar's extensive concern.Particularly different synthetic technologys unite use, for example: the combination of biocatalysis synthetic technology (as: enzymatic polymerization) and chemical catalysis synthetic technology (as: atom transfer radical polymerization).They not only for the polymkeric substance of synthetic various special constructions, provide effective scientific method as block, grafting, star, annular, hyperbranched polymer, and also the modification for various organic or inorganic materials provides novel technology.
Atom transfer radical polymerization (ATRP) is a kind of novel polymeric method, has activity, controlled characteristics, can realize the meticulous design of molecule segment structure.Its function monomer scope that is suitable for is wide, can be used for the controllable polymerization of nearly all vinyl monomer except alkene; Can carry out under the reaction conditions gentleness, room temperature; The polymerization means are various, can adopt multiple modes such as body, solution, suspension, emulsion to carry out; Can accurately synthesize the macromolecular material as different topology structures such as block, random, grafting, comb type, star-like, hyperbranched polymer and hybrids.Enzymatic polymerization (enzymatic polymerization) is the polymerization process of a kind of " green " environmental protection, and good chemo-selective, enantioselectivity and regioselectivity are arranged; The immobilized enzyme reusable edible; Can mass polymerization to avoid the use of organic solvent, be conducive to environmental protection; The use of lipase has substituted traditional poisonous transition-metal catalyst (as organo-aluminium compound, IV B family metal catalyst, rare-earth compounds, zinc and the magnesium compound of nitrogen oxygen coordination, tin compound stannous octoate Sn (Oct)
2Deng) use; The high molecular polymer that forms, generally biodegradable, have excellent biological compatibility simultaneously and utilize enzymic catalytic reaction to Substratspezifitaet, stereoselectivity and the characteristics that can reuse, the scientific worker utilizes the enzymatic polymerization reaction successfully to synthesize the polymer novel material of many excellent propertys such as chiral intermediate, Biodegradable material, slow releasing pharmaceutical carrier, medical macromolecular materials.
One pot of synthetic technology is the brand-new synthetic technology that latest developments are got up, building-up process has that reaction process is simplified, energy-efficient and characteristics that productive rate is high, avoided the separation of needed midbody compound in the multistep operation to purify, reduced the pollution that solvent brings, reduced production costs.Therefore, exploring and develop " one kettle way " reaction is far reaching problem in the synthetic chemistry." one kettle way " is very fast in polymkeric substance synthetic field development, and its method also respectively has characteristics: Holger Frey utilizes sec-BuLi to synthesize triblock polymer (Macromolecules40:5241-5244 (2007)) as the method that initiator adds monomer continuously; The method that Fudan University adopts SET-LRP to combine with Click chemistry synthesizes triblock polymer for one pot; People such as Claudia Gordin adopt " one kettle way ", use three initiators to synthesize radial block polymer (Polym.Bull63:789 – 801 (2009)); The method that Chinese University of Science and Technology adopts ATRP-Click chemistry-ROP to unite use synthesizes ABC multi-arm star-type polymer (Polymer Chemistry47:3066 – 3077 (2009)).
Few for one pot of synthetic technology report of the chemical enzyme process that adopts ATRP to combine with enzymatic polymerization, Andreas Heise group has successively utilized two still step-by-step polymerizations, and block polymer has been synthesized in single still successive polymerization.People such as people such as Steven M.Howdle and Holger Frey are respectively at supercritical CO
2Utilize one pot of synthetic two block polymer of enzyme method and graftomer under the environment.Yet polymkeric substance is at supercritical CO
2The synthesis condition harshness is difficult in industrial realization under the condition, and these factors are all restricting application and the industrialization promotion thereof of chemical enzyme process synthetic polymer.
Summary of the invention
The technical problem to be solved in the present invention is to adopt bifunctional initiator, " one pot simultaneously of chemical enzyme process " block polymer synthesis that realization utilizes atom transfer radical polymerization (ATRP) to combine with enzymatic polymerization.That is, enzymatic polymerization and atom transfer radical polymerization are melted into a reaction system, under the reaction conditions of routine, by the different functional groups of bifunctional initiator, cause the polyreaction of two kinds of different polymerization mechanism simultaneously and carry out simultaneously.
Method of the present invention has merged the reaction conditions gentleness of enzymatic polymerization reaction, environmental protection, product has excellent opticity, advantage such as degradability and biocompatibility and atom transition free radical polymerization reaction active controlled, functional monomer is many, advantages such as molecule segment can design and one pot of synthetic reaction process are simplified, energy-efficient, avoided the separation of needed midbody compound in the multistep operation to purify, reduce the pollution that solvent brings, advantage such as reduce production costs, advance the application of enzyme one process for one-pot synthesis, for the block polymer of complex functionality provides polymerization process more simply and easily.Wherein, the bifunctional initiator trichloro-ethyl alcohol of employing is industrial raw material, and cost is low, and then avoids the loaded down with trivial details synthesis step of bifunctional initiator, is a kind of bifunctional initiator that effectively can be used for " one pot simultaneously of chemical enzyme process " block polymer synthesis.
Bi-block copolymer of the present invention has following structure:
-A-A-A-A-A-A-bifunctional initiator-B-B-B-B-B-B-
Wherein A is the enzymatic polymerization monomer, and the polymerization degree of enzymatic polymerization monomer is 10 ≦ n ≦ 500; B is the atom transfer radical polymerization monomer, and the polymerization degree of atom transfer radical polymerization monomer is 10 ≦ m ≦ 1000; Bifunctional initiator is trichloro-ethyl alcohol (TCE) or different bromo-butyric acid hydroxyl ethyl ester (HEBiB).
Described enzymatic polymerization monomer, as 6-caprolactone (CL), L-rac-Lactide (L-LA), 10-hydroxydecanoic acid (10-HD) etc.; Described atom transfer radical polymerization monomer, as vinylbenzene (St), dimethylaminoethyl methacrylate (DMAEMA), butyl methacrylate (BMA), methyl methacrylate (MMA), N-isopropylacrylamide vinyl monomers such as (NIPAM).
Bi-block copolymer preparation method of the present invention: the chemical enzyme process that enzymatic polymerization combines with atom transfer radical polymerization is one pot of synthetic polymer simultaneously, comprises the steps:
Step 1: with solid ingredient: the molecular sieve of immobilized lipase Novozyme-435, cuprous halide, many nitrogen ligands (if solid ingredient), activation (
Molecular sieve is through 1000 ℃ of retort furnace calcinations activation) and reaction monomers (if solid ingredient) be positioned over (0.1mmHg, 25 ℃) in the vacuum drier, dry 24h.Liquid ingredient: reaction monomers, homogeneous solvent (make the reaction system homogeneous phase as toluene, tetrahydrofuran (THF) etc., consumption is about the 25%-50% of reaction system total mass) and initiator fully deoxygenation before reaction.
Step 2: reaction flask through strict baking-vacuum outgas-applying argon gas cooling, behind the triplicate, is added the solid ingredient in the reaction system, sealing.Behind three vacuum outgas-applying argon gas, the liquid ingredient after the deoxygenation is added in the reaction flask by sampler, the reaction flask sealing is positioned over transfers to 60 ℃ of-90 ℃ of magnetic agitation in the constant temperature oil bath and react.Reaction times is 2h-48h, and cooling finishes reaction, with corresponding solvent (consumption is about 10-30 times of reaction system volume) dissolving, crosses neutral Al
2O
3Pillar is removed lipase and cuprous/many nitrogen ligands complex catalysis system, and filtrate concentrates back precipitation in precipitation agent (consumption is about 100-400 times that concentrates the after product volume) and removes small molecule monomer, and vacuum-drying to constant weight obtains bi-block copolymer.
The foregoing invention technical scheme can be expressed as follows:
10 ≦ n ≦ 500,10 ≦ m ≦ 1000 wherein.Bifunctional initiator end described in the above-mentioned preparation method is active halogen atom and hydroxyl, and halogen atom is used for causing atom transition free radical polymerization reaction, and hydroxyl is used for causing the enzymatic polyreaction.Namely, used bifunctional initiator, one end has primary hydroxyl can cause enzymatic polymerization (enzymatic polymerization) reaction, and the other end has the alpha-halogen ester group can cause atom transfer radical polymerization (ATRP) reaction, and i CH can be contained in the centre
2(0≤i≤8) are as different bromo-butyric acid hydroxyl ethyl ester (HEBiB); Perhaps its opposite side contains active halogen atom such as trichloro-ethyl alcohol (TCE) etc. and all can be used as bifunctional initiator.
The enzyme-catalyzed change system is immobilized lipase Novozyme435 in the method catalyst system of chemistry enzyme process while one pot of synthetic di-block copolymer, the atom transfer radical polymerization catalyst system is transistion metal compound and respective ligand thereof, comprising being the atom transfer radical polymerization catalyst system, can selective chlorination cuprous and 2,2-dipyridyl (CuCl/bpy), cuprous chloride and pentamethyl-diethylenetriamine (CuCl/PMDETA), cuprous chloride and three-(N, N-dimethylaminoethyl) amine (CuCl/Me
6TREN), cuprous bromide and 2,2-dipyridyl (CuBr/bpy), cuprous bromide and pentamethyl-diethylenetriamine (CuBr/PMDETA), cuprous bromide and three-(N, N-dimethylaminoethyl) amine (CuBr/Me
6TREN).
Bi-block copolymer preparation method of the present invention may be summarized to be:
A kind of chemical enzyme process is the method for one pot of synthetic di-block copolymer simultaneously, be the enzymatic polymerization monomer with 6-caprolactone (CL), L-rac-Lactide (L-LA) or 10-hydroxydecanoic acid (10-HD), be the atom transfer radical polymerization monomer with the vinyl monomer, be the enzyme-catalyzed change system with the immobilized lipase, be the atom transfer radical polymerization catalyst system with cuprous halide/many nitrogen ligands, with 2,2,2-ethapon (TCE) or different bromo-butyric acid hydroxyl ethyl ester (HEBiB) are initiator, be homogeneous solvent with toluene or tetrahydrofuran (THF), constitute reaction system; In reaction initial vacuum drying treatment, liquid ingredient is dissolved in homogeneous solvent before reaction before reaction with the solid ingredient in the reaction system, logical argon gas deoxygenation, and reaction flask cools off through overbaking, vacuum outgas, applying argon gas before reaction; In reaction flask, add the solid ingredient in the reaction system afterwards, vacuum outgas again, applying argon gas; Liquid ingredient after the deoxygenation is added in the reaction flask by sampler, and the reaction flask sealing places constant temperature oil bath to react 2-48h under 60-90 ℃ of magnetic agitation; Cooling adds dissolution with solvents, crosses neutral Al
2O
3Pillar is removed immobilized lipase and cuprous halide/many nitrogen ligands, and filtrate concentrates back precipitation in precipitation agent and removes small molecule monomer, and vacuum-drying to constant weight obtains bi-block copolymer; Wherein, the mol ratio of initiator, cuprous halide, many nitrogen ligands, enzymatic polymerization monomer and atom transfer radical polymerization monomer is 1: 1: 2: 114-1880: 122-1000, the consumption of immobilized lipase is 5% of enzymatic polymerization monomer by mass, the homogeneous solvent consumption is the 25%-50% of reaction system total mass, solvent load is 10-30 times of reaction system volume, and the precipitation agent consumption is 100-400 times that filtrate concentrates the after product volume.
Described atom transfer radical polymerization monomer can be selected vinylbenzene (St), dimethylaminoethyl methacrylate (DMAEMA), butyl methacrylate (BMA), methyl methacrylate (MMA), N-isopropylacrylamide (NIPAM); Described enzyme-catalyzed change system, preferred immobilized lipase Novozyme-435; Described cuprous halide can the cuprous or cuprous bromide of selective chlorination; Described many nitrogen ligands can be selected 2,2-dipyridyl, pentamethyl-diethylenetriamine (PMDETA) or three-(N, N-dimethylaminoethyl) amine (Me
6TREN).Described solvent can be selected chloroform; Described precipitation agent can be selected methyl alcohol.
The molecular sieve that can also add activation in reaction system places the reaction flask bottom, and the water-content in the control reaction system is beneficial to fully carrying out of reaction; The molecular sieve of described activation is
Molecular sieve is through 1000 ℃ of calcination activation.
Solid ingredient in the described reaction system can be at 0.1mmHg, 25 ℃ of following dry 24h in reaction initial vacuum drying treatment.
Because the utilization of technique scheme, the present invention has following advantage:
1, the present invention has successfully introduced bifunctional initiator 2,2, the 2-ethapon, it is a kind of common used in industry raw material, can directly obtain, and then avoid the loaded down with trivial details synthesis step of bifunctional initiator, be a kind of cheap and effectively can be used for the bifunctional initiator of one pot of block polymer synthesis of chemical enzyme process.
2, " the chemical enzyme process simultaneously one pot " synthetic technology that adopts has been avoided the complicated processes of the polymerization of many stills and single still multistep polymerization.Simplified polymerization process, advantages such as having avoided the separation of needed midbody compound in the multistep operation to purify, reduce pollution that solvent brings, reduce production costs, be energy-efficient.The supercritical CO of having avoided one pot of polymerization technique of chemical enzyme process to use
2Reaction conditions makes this method be easier to industry and promotes, for the block polymer of complex functionality provides method more simply and easily.
3, " chemical enzyme process simultaneously one pot " synthetic catalyst system can recycle, can use the reactor continuously feeding in industrial production, continues synthetic segmented copolymer.
4, have unique functional segments such as stereoisomerism, optically-active characteristic, biocompatibility, degradability and pH temperature sensitive in the block polymer that " one pot simultaneously of chemical enzyme process " synthesizes, in biological medicine, phase solubilizing agent, tensio-active agent, fields such as nano material have very big potential using value.
Description of drawings:
Fig. 1 is the 1H NMR(CDCl3 of the synthetic di-block copolymer PCL-b-PDMAEMA of embodiment 1) spectrogram.
Fig. 2 is the GPC spectrogram of the synthetic di-block copolymer PCL-b-PDMAEMA of embodiment 1.THF is as moving phase, and flow velocity is 1mL/min, does pervasive correction with monodispersed vinylbenzene standard specimen.Wherein A is PCL-b-PDMAEMA; B is hydrolyzed product PDMAEMA.
Fig. 3 is synthetic di-block copolymer P (the 10-HD)-b-PBMA's of embodiment 2
1H NMR(CDCl
3) spectrogram.
Fig. 4 is the GPC spectrogram of synthetic di-block copolymer P (the 10-HD)-b-PBMA of embodiment 2.THF is as moving phase, and flow velocity is 1mL/min, does pervasive correction with monodispersed vinylbenzene standard specimen.Wherein A is P (10-HD)-b-PBMA; B is hydrolyzed product PBMA.
Embodiment:
In order to be easy to further understand the present invention, the following example will be further elaborated the present invention, but embodiments of the present invention are not limited thereto.
Embodiment 1: one pot of synthetic di-block copolymer PCL-b-PDMAEMA of chemical enzyme process
Reaction flask behind the triplicate, adds the solid ingredient in the reaction system through strict baking vacuum outgas applying argon gas cooling: in advance the molecular sieve of dry good lipase Novozyme435 (enzymatic polymerization monomer caprolactone (CL) weight 5%), activation (
Molecular sieve is through 1000 ℃ of retort furnace calcinations activation), atom transfer radical polymerization catalyst system cuprous chloride/2,2-dipyridyl (CuCl/bpy), sealing.Behind three vacuum outgas-applying argon gas, with liquid ingredient caprolactone (CL, 2.13g), ATRP monomer dimethylaminoethyl methacrylate (DMAEMA) and initiator 2,2,2-ethapon (TCE) is dissolved in and feeds the argon gas deoxygenation in the 2mL toluene, add in the reaction flask with sampler, oil bath is put in the reaction flask sealing transfer to 70 ℃ of magnetic agitation and react.Behind the reaction 6h, cooling finishes reaction, with the dissolving of 20mL chloroform, crosses neutral Al
2O
3Pillar (200-300 order, column chromatography with) is removed lipase and cuprous/many nitrogen ligands complex system, and filtrate concentrates back precipitation in 200mL methyl alcohol and removes small molecule monomer, and vacuum-drying namely obtains target product PCL-b-PDMAEMA to constant weight, and productive rate is 85%.TCE: CuCl: bpy: CL wherein: the DMAEMA molar ratio is 1: 1: 2: 114: 157.
Fig. 1 is PCL-b-PDMAEMA's
1H NMR(CDCl
3) d ppm: the hydrogen proton 1 on the PCL segment wherein, 2,3,4,5,6 characteristic peaks lay respectively at 3.6ppm, 4.1ppm, 1.6pmm, 1.4ppm, 1.6ppm, 2.3ppm place, the hydrogen proton 8,9 on the PDMAEMA segment, 10,11,12 characteristic peaks lay respectively at 0.9-1.3ppm, 1.8ppm, 4.1ppm, 2.6ppm, 2.3ppm place, and the characteristic peak of the hydrogen proton 7 on the initiator TCE is positioned at the 4.1ppm place.
Fig. 2 is the GPC spectrogram of PCL-b-PDMAEMA, and we can see that PCL-b-PDMAEMA is symmetrical unimodal distribution from spectrogram, and its number-average molecular weight is Mn=30183g/mol, and the molecular weight polymolecularity is PDI=1.67.The number-average molecular weight of hydrolysis after product PDMAEMA is Mn=18312g/mol, and the molecular weight polymolecularity is PDI=1.27.
The synthetic technology that fully proves the utilization " one pot simultaneously of chemical enzyme process " of our success by nuclear-magnetism and gpc analysis has been synthesized di-block copolymer PCL-b-PDMAEMA.
Embodiment 2: one pot of synthetic di-block copolymer P of chemical enzyme process (10-HD)-b-PBMA
Reaction flask is through strict baking vacuum outgas applying argon gas cooling, behind the triplicate, add the solid ingredient in the reaction system: in advance the molecular sieve of dry good lipase Novozyme435 (enzymatic polymerization monomer 10-hydroxydecanoic acid (10-HD) weight 5%), activation (
Molecular sieve is through 1000 ℃ of retort furnace calcinations activation), atom transfer radical polymerization catalyst system cuprous chloride/2,2-dipyridyl (CuCl/bpy) and enzymatic polymerization monomer 10-HD(1.88g), sealing.Behind three vacuum outgas-applying argon gas, liquid ingredient ATRP butyl methacrylate (BMA) and the different bromo-butyric acid hydroxyl of initiator ethyl ester (HEBiB) are dissolved in feeding argon gas deoxygenation in the 2mL toluene, add in the reaction flask with sampler, oil bath is put in the reaction flask sealing transfer to 70 ℃ of magnetic agitation and react.Behind the reaction 4h, cooling finishes reaction, with the dissolving of 20mL chloroform, crosses neutral Al
2O
3Pillar (200-300 order, column chromatography with) is removed lipase and cuprous/many nitrogen ligands complex system, and filtrate concentrates back precipitation in 200mL methyl alcohol and removes small molecule monomer, and vacuum-drying namely obtains target product P (10-HD)-b-PBMA to constant weight, and productive rate is 79%.HEBiB: CuCl: bpy: 10-HD wherein: the BMA molar ratio is 1: 1: 2: 188: 141.
Fig. 3 is P (10-HD)-b-PBMA's
1H NMR(CDCl
3) the proton hydrogen of repeating unit produces on the d ppm:10-HD main chain characteristic peak appears at δ=2.3,1.6,1.3,1.6,4.05ppm (j, k, l, m, n) locates, and the characterization displacement study peak that occurs about δ=3.65ppm (o) is that terminal hydroxy group connects methylene radical hydrogen; The triplet that δ=0.8-1.0ppm (a, b) locates is the characteristic peak of the last two kinds of methyl of BMA, non-δ=1.8,1.4, the 1.8ppm (e, d, g) of not appearing at of three kinds of methylene radical characteristic peaks in the repeating unit, the methylene radical characteristic peak that connects oxygen appears at δ=3.95ppm (f) and locates.
Fig. 4 is the GPC spectrogram of P (10-HD)-b-PBMA, and we can see that P (10-HD)-b-PBMA is symmetrical unimodal distribution from spectrogram, and its number-average molecular weight is Mn=17300g/mol, and the molecular weight polymolecularity is PDI=1.13.The number-average molecular weight of hydrolysis after product PBMA is Mn=5800g/mol, and the molecular weight polymolecularity is PDI=1.23.
The synthetic technology that fully proves the utilization " one pot simultaneously of chemical enzyme process " of our success by nuclear-magnetism and gpc analysis has been synthesized di-block copolymer P (10-HD)-b-PBMA.
Embodiment 3: one pot of synthetic di-block copolymer PCL-b-PSt of chemical enzyme process
Reaction flask behind the triplicate, adds the solid ingredient in the reaction system through strict baking vacuum outgas applying argon gas cooling: in advance the molecular sieve of dry good lipase Novozyme435 (enzymatic polymerization monomer caprolactone (CL) weight 5%), activation (
Molecular sieve is through 1000 ℃ of retort furnace calcinations activation), atom transfer radical polymerization catalyst system cuprous chloride/2,2-dipyridyl (CuCl/bpy), sealing.Behind three vacuum outgas-applying argon gas, with liquid ingredient caprolactone (CL, 2.13g), ATRP monomer styrene (St) and initiator 2,2,2-ethapon (TCE) is dissolved in and feeds the argon gas deoxygenation in the 2mL toluene, add in the reaction flask with sampler, oil bath is put in the reaction flask sealing transfer to 70 ℃ of magnetic agitation and react.Behind the reaction 7h, cooling finishes reaction, with the dissolving of 20mL chloroform, crosses neutral Al
2O
3Pillar (200-300 order, column chromatography with) is removed lipase and cuprous/many nitrogen ligands complex system, and filtrate concentrates back precipitation in 200mL methyl alcohol and removes small molecule monomer, and vacuum-drying namely obtains target product PCL-b-PSt to constant weight, and productive rate is 80%.TCE: CuCl: bpy: CL wherein: the St molar ratio is 1: 1: 2: 114: 160.The product number-average molecular weight is Mn=52781g/mol, and the molecular weight polymolecularity is PDI=1.62.
Embodiment 4: one pot of synthetic di-block copolymer PCL-b-PMMA of chemical enzyme process
Reaction flask behind the triplicate, adds the solid ingredient in the reaction system through strict baking vacuum outgas applying argon gas cooling: in advance the molecular sieve of dry good lipase Novozyme435 (enzymatic polymerization monomer caprolactone (CL) weight 5%), activation (
Molecular sieve is through 1000 ℃ of retort furnace calcinations activation), atom transfer radical polymerization catalyst system cuprous chloride/2,2-dipyridyl (CuCl/bpy), sealing.Behind three vacuum outgas-applying argon gas, with liquid ingredient caprolactone (CL, 2.13g), ATRP monomers methyl methacrylate (MMA) and initiator 2,2,2-ethapon (TCE) is dissolved in and feeds the argon gas deoxygenation in the 2mL toluene, add in the reaction flask with sampler, oil bath is put in the reaction flask sealing transfer to 60 ℃ of magnetic agitation and react.Behind the reaction 6h, cooling finishes reaction, with the dissolving of 20mL chloroform, crosses neutral Al
2O
3Pillar (200-300 order, column chromatography with) is removed lipase and cuprous/many nitrogen ligands complex system, and filtrate concentrates back precipitation in 200mL methyl alcohol and removes small molecule monomer, and vacuum-drying namely obtains target product PCL-b-PMMA to constant weight, and productive rate is 88%.TCE: CuCl: bpy: CL wherein: the MMA molar ratio is 1: 1: 2: 114: 122.The product number-average molecular weight is Mn=32693g/mol, and the molecular weight polymolecularity is PDI=1.32.
Embodiment 5: one pot of synthetic di-block copolymer P of chemical enzyme process (10-HD)-b-PMMA
Except the butyl methacrylate monomer adopted methyl methacrylate, other all are same as step among the embodiment 2, wherein HEBiB: CuCl: bpy: 10-HD: the MMA molar ratio is 1: 1: 2: 1880: 1000, the reaction times was 48h.The product number-average molecular weight is Mn=212693g/moL, and the molecular weight polymolecularity is PDI=1.32.Productive rate is 70%.
Embodiment 6: one pot of synthetic di-block copolymer P of chemical enzyme process (10-HD)-b-PNIPAM
Except the butyl methacrylate monomer adopts N-isopropylacrylamide (NIPAM), the atom transfer radical polymerization catalyst system adopts CuCl/PMDETA, other all are same as step among the embodiment 2, HEBiB: CuCl: PMDETA: 10-HD wherein: the NIPAM molar ratio is 1: 1: 2: 188: 200, temperature of reaction is 90 ℃, and the reaction times is 8h.The product number-average molecular weight is Mn=30478g/mol, and the molecular weight polymolecularity is PDI=1.46, and productive rate is 64%.
Claims (6)
1. the chemical enzyme process method of one pot of synthetic di-block copolymer simultaneously, be the enzymatic polymerization monomer with 6-caprolactone, L-rac-Lactide or 10-hydroxydecanoic acid, be the atom transfer radical polymerization monomer with the vinyl monomer, being the enzyme-catalyzed change system with the immobilized lipase, is the atom transfer radical polymerization catalyst system with cuprous halide/many nitrogen ligands, with 2,2,2-ethapon or different bromo-butyric acid hydroxyl ethyl ester are initiator, are homogeneous solvent with toluene or tetrahydrofuran (THF), constitute reaction system; In reaction initial vacuum drying treatment, liquid ingredient is dissolved in homogeneous solvent before reaction with the solid ingredient in the reaction system, logical argon gas deoxygenation, and reaction flask cools off through overbaking, vacuum outgas, applying argon gas before reaction; In reaction flask, add the solid ingredient in the reaction system afterwards, vacuum outgas again, applying argon gas; Liquid ingredient after the deoxygenation is added in the reaction flask by sampler, and the reaction flask sealing places constant temperature oil bath to react 2-48h under 60-90 ℃ of magnetic agitation; Cooling adds dissolution with solvents, crosses neutral Al
2O
3Pillar is removed immobilized lipase and cuprous halide/many nitrogen ligands, and filtrate concentrates back precipitation in precipitation agent and removes small molecule monomer, and vacuum-drying to constant weight obtains bi-block copolymer; Wherein, the mol ratio of initiator, cuprous halide, many nitrogen ligands, enzymatic polymerization monomer and atom transfer radical polymerization monomer is 1: 1: 2: 114-1880: 122-1000, the consumption of immobilized lipase is 5% of enzymatic polymerization monomer by mass, the homogeneous solvent consumption is the 25%-50% of reaction system total mass, solvent load is 10-30 times of reaction system volume, and the precipitation agent consumption is 100-400 times that filtrate concentrates the after product volume.
2. the chemical enzyme process according to claim 1 method of one pot of synthetic di-block copolymer simultaneously, it is characterized in that, described atom transfer radical polymerization monomer is vinylbenzene, dimethylaminoethyl methacrylate, butyl methacrylate, methyl methacrylate or N-isopropylacrylamide; Described enzyme-catalyzed change system is immobilized lipase Novozyme-435; Described cuprous halide is cuprous chloride or cuprous bromide; Described many nitrogen ligands are 2,2-dipyridyl, pentamethyl-diethylenetriamine or three-(N, N-dimethylaminoethyl) amine; Described solvent is chloroform; Described precipitation agent is methyl alcohol.
3. the method for chemical enzyme process while one pot of synthetic di-block copolymer according to claim 1 is characterized in that, the solid ingredient in the described reaction system is at 0.1mmHg, 25 ℃ of following dry 24h in reaction initial vacuum drying treatment.
4. according to the method for claim 1,2 or 3 described chemical enzyme process while one pot of synthetic di-block copolymer, it is characterized in that, in reaction system, add the molecular sieve of activation, place the reaction flask bottom; The molecular sieve of described activation is
Molecular sieve is through 1000 ℃ of calcination activation.
5. the synthetic di-block copolymer of method of chemical enzyme process while one pot of synthetic di-block copolymer of a claim 1 has following structure,
-A-A-A-A-A-A-bifunctional initiator-B-B-B-B-B-B-,
Wherein A is the enzymatic polymerization monomer, and the polymerization degree of enzymatic polymerization monomer is 10 ≦ n ≦ 500; B is the atom transfer radical polymerization monomer, and the polymerization degree of atom transfer radical polymerization monomer is 10 ≦ m ≦ 1000; Bifunctional initiator is trichloro-ethyl alcohol or different bromo-butyric acid hydroxyl ethyl ester.
6. the method for di-block copolymer according to claim 5 is characterized in that, described enzymatic polymerization monomer is 6-caprolactone, L-rac-Lactide or 10-hydroxydecanoic acid; Described atom transfer radical polymerization monomer is vinylbenzene, dimethylaminoethyl methacrylate, butyl methacrylate, methyl methacrylate or N-isopropylacrylamide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013101557145A CN103242497A (en) | 2013-05-01 | 2013-05-01 | Method for synthesising diblock copolymer by simultaneous chemoenzymatic process and one-pot process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013101557145A CN103242497A (en) | 2013-05-01 | 2013-05-01 | Method for synthesising diblock copolymer by simultaneous chemoenzymatic process and one-pot process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103242497A true CN103242497A (en) | 2013-08-14 |
Family
ID=48922397
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2013101557145A Pending CN103242497A (en) | 2013-05-01 | 2013-05-01 | Method for synthesising diblock copolymer by simultaneous chemoenzymatic process and one-pot process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103242497A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107099007A (en) * | 2017-04-24 | 2017-08-29 | 浙江理工大学 | Polymer composite vesica of Amphipathilic block polymer, light and pH double-responses and its preparation method and application |
| CN111690111A (en) * | 2020-07-30 | 2020-09-22 | 中国科学院兰州化学物理研究所 | Comb type polymer and preparation method and application thereof |
| CN115124669A (en) * | 2022-05-27 | 2022-09-30 | 北京化工大学 | Preparation method and application of linear block copolymer nano-carrier with double-carrier genes and medicines |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101928741A (en) * | 2010-07-23 | 2010-12-29 | 南京工业大学 | Production method for preparing endomorphin-1 in organic medium system by chemical enzyme method |
-
2013
- 2013-05-01 CN CN2013101557145A patent/CN103242497A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101928741A (en) * | 2010-07-23 | 2010-12-29 | 南京工业大学 | Production method for preparing endomorphin-1 in organic medium system by chemical enzyme method |
Non-Patent Citations (2)
| Title |
|---|
| 沙柯等: "利用酶促开环聚合和原子转移自由基聚合方法合成AB型嵌段共聚物", 《高等学校化学学报》 * |
| 王薇: "化学酶法合成嵌段共聚物及其自组装的研究", 《中国博士学位论文全文数据库工程科技I辑》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107099007A (en) * | 2017-04-24 | 2017-08-29 | 浙江理工大学 | Polymer composite vesica of Amphipathilic block polymer, light and pH double-responses and its preparation method and application |
| CN107099007B (en) * | 2017-04-24 | 2019-03-12 | 浙江理工大学 | Polymer composite vesica of Amphipathilic block polymer, light and pH double-response and its preparation method and application |
| CN111690111A (en) * | 2020-07-30 | 2020-09-22 | 中国科学院兰州化学物理研究所 | Comb type polymer and preparation method and application thereof |
| CN115124669A (en) * | 2022-05-27 | 2022-09-30 | 北京化工大学 | Preparation method and application of linear block copolymer nano-carrier with double-carrier genes and medicines |
| CN115124669B (en) * | 2022-05-27 | 2024-03-26 | 北京化工大学 | Preparation method and application of linear block copolymer nano-carrier for double-gene and medicine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6114482A (en) | Process for the controlled radical polymerization or copolymerization of (meth) acrylic and vinyl monomers and (co) polymers obtained | |
| US9228044B2 (en) | Versatile, facile and scalable route to polylactic acid-backbone graft and bottlebrush copolymers | |
| CN107022069A (en) | Method for catalyzing ring-opening polymerization of gamma-valerolactone by utilizing biomimetic catalyst | |
| CN110003481A (en) | A kind of preparation method of the miscellaneous arm star polymer of eight arms | |
| CN106046038B (en) | A kind of 8 N arylamine hydrogenated quinolines complexing alkyl aluminum compound and preparation method and application | |
| CN101906195B (en) | Star polymer and method for producing the same | |
| CN103242497A (en) | Method for synthesising diblock copolymer by simultaneous chemoenzymatic process and one-pot process | |
| CN102690217A (en) | Preparation method for efficient chain transfer agent trithiocarbonate used for RAFT (reversible addition-fragmentation chain transfer) polymerization | |
| Yi et al. | Asymmetric epoxidation of α, β-unsaturated ketones catalyzed by silica-grafted poly-(l)-leucine catalysts | |
| CN112778505A (en) | Synthesis method of gradual change type polyester | |
| CN105801825A (en) | Method for synthesizing amphiphilic polymer comprising multiple bromine functional groups and its cationizable grafted copolymer by copolymerization of catalytic cyclic lactone | |
| Habaue et al. | Chemospecific ring-opening polymerization of α-methylenemacrolides | |
| CN105622788B (en) | Three arm ATRP initiators and its preparation and application with planar conjugate structure | |
| CN105037588A (en) | Isoindole rare earth metal catalyst, preparation method and application | |
| Shen et al. | Complex of hyperbranched polyethylenimine with cuprous halide as recoverable homogeneous catalyst for the atom transfer radical polymerization of methyl methacrylate | |
| CN110776588B (en) | Method for preparing chloride of polymer containing unsaturated double bond structural unit and method for preparing polymer brush by using chloride | |
| CN103140496A (en) | Carboxylate metal complex and catalyst for olefin polymerization | |
| CN108148188A (en) | A kind of combed petchem and preparation method thereof | |
| CN104592425B (en) | A kind of cycloheptatriene base rare-earth metal catalyst, preparation method and application | |
| EP2390274B1 (en) | Polyfunctional polymer of high stereoregularity and method for producing the same | |
| CN113527190B (en) | Pyridine imine ligand, pyridine imine nickel palladium complex based on ligand and application of pyridine imine nickel palladium complex in catalyzing ethylene polymerization reaction | |
| CN101885816B (en) | Method for preparing poly(styrene-b-acrylonitrile) by two-step polymerization method | |
| CN103242537B (en) | Method for synthesising grafted copolymer by simultaneous chemoenzymatic process and one-pot process | |
| WO2021260392A1 (en) | Polymer | |
| CN109679080B (en) | Method for catalyzing caprolactone polymerization by using amine imine magnesium complex |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130814 |