A method for preparing functionalized polymers based on macro-microreactor chemistry-enzymatic method

Abstract

The application discloses a method for preparing functionalized polymers based on macro-micro reactor chemical-enzyme method, and the method comprises the following steps: reacting a mixed solution of acrylate monomers, an initiator, a ligand, a functional alcohol and a solvent in a micro reactor to obtain a reaction liquid containing functionalized polyacrylate, wherein the micro reactor comprises a macro-micro reactor containing copper inner components. In the macro-micro reactor, enzymatic transesterification and Cu(0)-RDRP coupling reaction are coupled to obtain a series of poly(meth)acrylates and copolymers with chemical structures. Compared with traditional synthesis methods, the macro-micro reactor containing the inner components can significantly shorten the polymerization time, avoid secondary purification of monomers, and greatly improve the conversion rate. The characteristic scale of the macro-micro reactor reaches the centimeter level, and high-throughput synthesis can be realized. The application provides a technical scheme for preparing functionalized poly(meth)acrylate polymers, and has industrialization conversion prospects.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of polymer synthesis, and particularly relates to a method for preparing functionalized polymers based on macro-micro reactor chemical-enzyme method. BACKGROUND

[0002] This section provides background information only and is not necessarily prior art.

[0003] Functionalized polyacrylates are an important class of polymer materials that can be used to produce products with excellent properties such as heat resistance, water resistance, and ultraviolet resistance. For example, new functionalized acrylates can be used in industry to synthesize high-performance polymers, coatings, adhesives, and other chemicals, to manufacture materials that are resistant to chemical corrosion, high-strength, and high-transparency. In pharmaceutical chemistry, they can be used to manufacture drug delivery systems, control drug release rate and duration, and improve drug treatment effect and reduce adverse reactions. In biology and biomedical science, they can be used to manufacture biosensors, biochips, and biomedical materials. Traditional chemical preparation is to use transition metals as catalysts to catalyze ester exchange reactions, and introduce them in situ into ATRP polymerization to polymerize different monomers in sections to obtain polymers.

[0004] Enzymatic method is one of the green methods for preparing functionalized acrylates. Coupling enzymatic method with chemical catalysis can efficiently prepare functionalized polyacrylates. For example, combining enzymatic ester exchange monomer synthesis with light-controlled polymerization technology, through photo-induced reversible addition-fragmentation chain transfer polymerization (PET-RAFT), high monomer conversion rate (~100%) and good end group integrity (>80%) are achieved. By continuously adding monomers, different multi-block copolymers are quickly synthesized without purification steps. Not only is it efficient and convenient to obtain products with complex structure and function, but also the synthesis steps are simplified and the synthesis cost is reduced, embodying the concept of green chemistry and sustainable development, which is increasingly attracting attention from the chemical and industrial communities. However, in the use of traditional batch reactors, there are a series of problems such as enzyme deactivation and low conversion rate caused by vigorous stirring, and how to improve the yield and increase the reuse of enzymes has become a new challenge.

[0005] Enzymes are considered as green and efficient catalysts, with high chemical selectivity, regioselectivity, and stereoselectivity in the reaction process. Candida antarctica lipase A (CALB) is a lipase derived from Candida antarctica, and its commercial name is Novozyme 435. Due to its excellent selectivity, thermal stability, and catalytic activity, it is widely used in catalyzing ester exchange reactions, ring-opening polymerization, esterification reactions, and polycondensation reactions, etc.

[0006] Copper(0)-mediated reversible-deactivation radical polymerization(RDRP) is a kind of living radical polymerization with Cu(0) as the only catalyst, which has the advantages of simple and mild reaction conditions, fast polymerization of acrylate, etc., and is used to prepare various structures of small molecule homopolymers, block copolymers, complex structure polymers, functional polymers, functional surfaces and biological coupling. The metal Cu(0) exists in the form of wire or powder, and the reaction rate can be adjusted by changing the surface area. After polymerization, the unused Cu(0) can be removed from the polymer solution and reused for new reactions. In recent years, Cu(0)-mediated RDRP(Cu(0)-RDRP) in continuous flow microreactors has attracted more and more attention, which greatly promotes the possibility of industrial application.

[0007] In traditional tank reactors, enzyme-catalyzed transesterification reactions and controlled radical polymerization reactions have orthogonality, and functional polyacrylates can be prepared by "one-pot method", but there are problems such as difficulty in enzyme recovery, easy deactivation, long reaction time, poor controllability of reaction, etc.

[0008] By introducing microreactors, their small size has high specific surface area and volume ratio, thereby enhancing mass and energy transfer, improving reaction rate, reducing diffusion distance and reactant residence volume, thereby providing advantages for process intensification, which can overcome the problems of long reaction time in tank reactors, but the yield needs to be improved. The present application is based on macro-micro reactor for chemical-enzyme coupling reaction, which greatly shortens the reaction time of enzyme-catalyzed transesterification and polymerization, and successfully improves the conversion rate, and the characteristic scale of macro-micro reactor can reach centimeter level, which can realize high-throughput synthesis. SUMMARY

[0009] The technical problem to be solved by the present application is to overcome the shortcomings of the prior art, and to provide a method for preparing functional polymers based on macro-micro reactor chemical-enzyme method.

[0010] The present application provides a novel macro-micro reactor, which couples biological catalysis and chemical catalysis in a microfluidic reaction platform, and efficiently prepares functional polyacrylates with narrow distribution and controllable structure by adjusting the reaction conditions.

[0011] To solve the above technical problems, the present application discloses the following technical solutions:

[0012] In a first aspect, the present application discloses a method for preparing functional polymers by macro-continuous flow chemical-enzyme method, which comprises reacting a mixed solution of acrylate monomers, initiator, ligand, functional alcohol and solvent in a macro-continuous flow chemical-enzyme microreactor to obtain a reaction solution containing functional polyacrylates.

[0013] In some embodiments, the macro-continuous flow chemical-enzymatic microreactor is an enzyme-containing macro-microreactor; the macro-microreactor contains copper inner components; in some embodiments, the macro-microreactor is a traditional continuous flow chemical-enzymatic microreactor, which is a copper pipe.

[0014] In a second aspect, the application discloses an application of a macro-microreactor in preparation of a functional polymer, a mixed solution of an acrylate monomer, an initiator, a ligand, a functional alcohol and a solvent is reacted in a microreactor to obtain a reaction solution containing a functional polyacrylate; the macro-microreactor contains copper inner components.

[0015] In the above-mentioned first aspect and second aspect,

[0016] The reaction involves simultaneous ester exchange reaction and Cu(0)-mediated controlled radical polymerization, in particular:

[0017]

[0018] wherein n and m are independently selected from any number in the range of 5-300; R1 is selected from H or methyl; R2 is selected from methyl, butyl, cyclohexyl, benzyl, -CH2CF3; R3 is selected from methyl, n-propyl, i-propyl, n-butyl, t-butyl, n-hexyl, furfuryl, morpholinoethyl, n-undecyl, triethyleneglycol methoxy and propionitrile; R4 is selected from methylpropionoethyl, phenylacetoethyl, methylmalono-diethyl, isobutyro-glycol, propionomethyl, propionoethyl, propionitrile and PHCOCH-; and X is selected from Br or Cl.

[0019] The reaction process is as follows, taking the monomer trifluoroacrylate as an example, wherein the trifluoroacrylate acts as a monomer for Cu(0)-mediated controlled radical polymerization and a substrate for enzymatic ester exchange reaction, and copper acts as a catalyst for polymerization reaction; in the enzyme microreactor, the ester exchange reaction and the Cu(0)-mediated controlled radical polymerization are simultaneously carried out; the monomer trifluoroacrylate and the functional alcohol in the system undergo ester exchange to generate an R-acrylate; the trifluoroacrylate and the R-acrylate simultaneously participate in the polymerization reaction to prepare a functional polyacrylate, thus showing the characteristics of copolymerization.

[0020]

[0021] wherein x and y are independently selected from any number in the range of 5-300; R is selected from methyl, n-propyl, i-propyl, n-butyl, t-butyl, n-hexyl, furfuryl, morpholinoethyl, n-undecyl, triethyleneglycol methoxy and propionitrile.

[0022] The present application can successfully prepare polytrifluoroethyl acrylate (PTFEA) and poly-n-hexyl acrylate (PHA) with a ratio of 1 / 1 and PTFEA-co-PHA dominated by PTFEA by reducing the monomer concentration (increasing the solvent content), thereby reducing the enzymatic transesterification rate, such as when the functional alcohol is n-hexanol. That is, when the transesterification rate is higher, the functional polymer structure is dominated by poly-n-hexyl acrylate, and when the rate is lower, the structure is dominated by polytrifluoroethyl acrylate, and a one-pot method can be used to prepare copolymers with different structures.

[0023] wherein the monomer is any one or combination of trifluoroethyl acrylate, methyl methacrylate, trifluoroethyl methacrylate, methyl acrylate, n-butyl acrylate, benzyl acrylate and cyclohexyl acrylate, preferably any one or combination of trifluoroethyl acrylate, benzyl acrylate and cyclohexyl acrylate, and further preferably trifluoroethyl acrylate.

[0024]

[0025] wherein the initiator is any one or combination of ethyl 2-bromo-2-methylpropionate, ethyl α-bromophenylacetate, diethyl 2-bromo-2-methylmalonate, ethylene glycol bromoisobutyrate, methyl 2-chloropropionate, 2,2-dichloroacetophenone, ethyl 2-chloropropionate and 2-bromopropionitrile, preferably any one or combination of ethyl 2-bromo-2-methylpropionate and ethyl α-bromophenylacetate, and further preferably ethyl 2-bromo-2-methylpropionate; preferably, the molar ratio of the initiator to the monomer is 1:100-1000, such as 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900.

[0026]

[0027] wherein the ligand is tris(2-dimethylaminoethyl)amine and / or 4,4'-dinonyl-2,2'-bipyridine, preferably tris(2-dimethylaminoethyl)amine; preferably, the molar ratio of the initiator to the ligand is 1:0.1-1, preferably 1:0.25-0.5, and further preferably 1:0.25.

[0028] wherein the functional alcohol is any one or combination of methanol, n-propanol, isopropanol, n-butanol, tert-butanol, n-hexanol, furfuryl alcohol, undecanol, 2-morpholinoethanol, triethylene glycol monomethyl ether and 3-hydroxypropionitrile; preferably, the molar ratio of the initiator to the functional alcohol is 1:100-1200, such as 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, 1:1000, 1:1100.

[0029]

[0030] The solvent is any one or a combination of several of dimethyl sulfoxide, tetrahydrofuran, N,N-dimethylformamide, and toluene, preferably dimethyl sulfoxide; preferably, the concentration of the monomer is 1-5 mol / L; the concentration of the monomer = (n 单体 ) / (V 单体 +V 功能化醇 +V 溶剂 ).

[0031] In this invention, the reaction apparatus is as follows: Figure 1 The experiment is conducted in a reaction apparatus containing a macro-continuous flow chemical-enzymatic microreactor (filled with lipase) or a conventional continuous flow chemical-enzymatic microreactor (filled with lipase). The reaction apparatus includes a feed pump, a syringe, any one of the aforementioned microreactors, and a receiving device. The feed pump, syringe, microreactor, and receiving device are connected in series via pipelines. The microreactor is equipped with a heating device. The pipelines of the microreactor are repeatedly flushed with toluene or tetrahydrofuran before each use to purify them.

[0032] The method for preparing the macro-continuous flow chemical-enzymatic microreactor is as follows: a hollowed-out copper inner component (diameter 0.5–3 mm, e.g., 0.5–1 mm) and an immobilized enzyme are placed inside a microchannel tube with an inner diameter of 2–15 mm (e.g., 2–4.3 mm); the copper inner component includes a copper spiral. In some embodiments, the copper inner component is a spiral-shaped inner component, a serpentine inner component, an O-shaped inner component, or a straight inner component; the spiral-shaped inner component, the serpentine inner component, and the O-shaped inner component have a pitch of 0.5–10 mm, e.g., 1–3 mm.

[0033] In this embodiment, the conventional continuous flow chemical-enzymatic microreactor involves placing an immobilized enzyme inside a microchannel tube with an inner diameter of 1 to 4.5 mm, such as 4.3 mm or 4.5 mm; in some embodiments, the microchannel tube is a copper tube.

[0034] The retention volume of the macro-micro reactor is 1 to 20 mL, such as 1, 3, 5, 10, or 15 mL.

[0035] The copper tubes and copper spirals require activation. The activation method is as follows: 20 mL of dilute sulfuric acid solution is drawn into a syringe and flushed into the tubes at a flow rate of 0.333 mL / min for 60 min. Then, another 20 mL of distilled water is drawn into the tubes and flushed into the tubes at a flow rate of 4 mL / min for 5 min to remove Cu2O and CuO from the copper surface. Then, 20 mL of trifluoroethanol is drawn into the tubes and flushed into the tubes at a flow rate of 0.333 mL / min for 60 min. Finally, the continuous flow reactor is dried under a nitrogen atmosphere to minimize the oxygen in the system.

[0036] wherein the control immobilized enzyme is loaded in the microchannel tubing at a loading of 0.3-1 g / mL, such as 0.3, 0.5, 0.6, 0.8 g / mL; fresh enzyme is added before each use and the ends of the tubing are secured with a small amount of cotton, and the enzyme is removed after use.

[0037] wherein the immobilized enzyme is any one or a combination of immobilized lipases, such as Candida antarctic lipase B (CALB), Candida rugosa lipase, Amano Lipase from Pseudomonas fluorescens, and lipase PS from Burkholderia cepacia (LPS), preferably Candida antarctic lipase B (CALB), i.e., immobilized Novozyme 435 lipase, with an enzyme activity of 10,000 PLU / g.

[0038] wherein the mixed solution is prepared by mixing an acrylate monomer, an initiator, a ligand, a functional alcohol, and a solvent under inert gas protection; the mixed solution is reacted after removal of dissolved oxygen; preferably, the removal of dissolved oxygen is performed by bubbling or liquid nitrogen freezing-vacuum-dissolving.

[0039] wherein the reaction temperature is 0-100°C, such as 40°C, 60°C.

[0040] wherein the reaction rate is 0.0033-25 mL / min, such as 0.0067-0.5 mL / min.

[0041] wherein the reaction retention time is 2-300 min, such as 10-300 min, preferably 10-150 min.

[0042] wherein after the reaction, the reaction solution is quenched, an organic precipitant is added, and centrifugal separation is performed to obtain a solid functionalized polyacrylate; preferably, the quenching agent is liquid nitrogen; preferably, the organic precipitant is a mixed solution of methanol and water, methanol, or n-hexane. In some embodiments, the temperature of the organic precipitant is -20°C; the amount of the organic precipitant is 20-100 times the volume of the reaction solution; preferably, the precipitant is centrifugally separated after 2 hours; more preferably, the centrifugally obtained substance is dissolved in toluene or tetrahydrofuran, and then precipitated with an organic precipitant, and the purification is performed by repeating this step three times; the product after purification is vacuum dried.

[0043] The solid functionalized polyacrylate obtained by the reaction of different monomer concentrations has a controllable sequence structure after the reaction is completed.

[0044] In the present application, a copper inner member is placed in a microchannel to form a macro-micro reactor, and a mixed solution of acrylate monomers, initiators, ligands, functional alcohols and solvents is reacted in the macro-micro reactor to obtain functionalized polyacrylate. The polymerization reaction rate in the copper-containing inner member macro-micro reactor provided by the present application is better than that in a copper pipe, and even better than that in copper powder. The present application couples copper-catalyzed controllable free radical polymerization with enzymatic transesterification reaction, and the two do not interfere with each other, realizes chemical-enzyme coupling, and through changing the solvent concentration, the enzyme catalytic rate can be regulated to efficiently prepare functionalized polyacrylate copolymers with narrow distribution and controllable structure.

[0045] Advantages: Compared with the prior art, the present application has the following advantages:

[0046] (1) The present application is based on the macro-micro reactor to intensify the chemical-enzyme coupling reaction process, and a series of chemical structure poly(meth)acrylate copolymers are prepared quickly and with high throughput.

[0047] (2) Compared with the traditional tank reactor, the present application is based on the macro-micro reactor to significantly improve the polymerization conversion rate and reduce the molecular weight distribution index. For example, in the same reaction time of 60 min, the polymerization conversion rate of trifluoroethyl acrylate and n-hexanol is increased from 23.08% to 63.23%, and the molecular weight distribution index is reduced from 1.42 to 1.14.

[0048] (3) Compared with the typical micro-reactor (characteristic scale = 1.0 mm), the present application is based on the macro-micro reactor to significantly increase the reaction flux, for example, the flow rate is increased from 0.006667 ml / min to 0.01667 ml / min, and the output per unit time is increased from 0.0292 g / min to 0.0445 g / min.

[0049] (4) Compared with the continuous flow reactor (>2.0 mm without inner member), the present application is based on the macro-micro reactor to significantly improve the conversion rate and reduce the distribution index. For example, under the same reaction time, the polymerization conversion rate is increased from 44.79% to 63.23%, and the distribution index is reduced from 1.22 to 1.14. BRIEF DESCRIPTION OF DRAWINGS

[0050] The above and / or other aspects of the present application will become apparent and more readily appreciated from the following description, taken in conjunction with the accompanying drawings in which:

[0051] Figure 1 Schematic diagram of the macro-micro reactor system used in the present experiment.

[0052] Figure 2 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1 1 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1

[0053] Figure 3 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1 1 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1

[0054] Figure 4 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1 1 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1

[0055] Figure 5 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1 1 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1

[0056] Figure 6 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1 1 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1

[0057] Figure 7 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1 1 H NMR chart of the functionalized poly (trifluoroethyl acrylate-co-n-hexyl acrylate) of Example 1 DETAILED DESCRIPTION

[0058] The present application can be better understood in accordance with the following examples. It will be readily apparent to those skilled in the art, however, that the

[0059] The experimental methods described in the following examples are conventional unless otherwise specified, and the reagents and materials are commercially available unless otherwise specified.

[0060] The following methods were used in the following examples to measure the number average molecular weight and molecular weight distribution of the products.

[0061] Wyatt size exclusion chromatography system was used, with tetrahydrofuran as the mobile phase, a flow rate of 0.7 mL / min, a column temperature of 35°C, and an injection volume of 0.4 mL.

[0062] Sample measurement: take 2mg pure sample in centrifuge tube, add 1mL tetrahydrofuran solution for dilution, then filter with disposable filter head (containing 0.33m organic filter membrane), take 0.4mL solution for sample measurement.

[0063] The structure of the polymerization product was characterized by 400MHz Bruker nuclear magnetic resonance instrument through 1 H NMR and 13 C NMR. Take 10mg sample in nuclear magnetic tube, add deuterated chloroform, shake until completely dissolved, then measure the sample.

[0064] In the following examples, Candida antarctic lipase B (CALB) was used; the particle size was 0.3-0.9mm; the enzyme activity was 10000PLU / g; the purchasing distributor was Nanjing Deming Chemical Technology Co., Ltd. Lipase (pocine pancreas); the enzyme activity was 30000U / g; the purchasing distributor was Shanghai Yuanye Biotechnology Co., Ltd. Lipase from Candida rugosa; the enzyme activity was 700U / mg; the purchasing distributor was Shanghai Yuanye Biotechnology Co., Ltd. Amano Lipase from Pseudomonas fluorescens; the enzyme activity was 20000U / g; the purchasing distributor was Merck Co., Ltd. Lipase PS from Burkholderia cepacia (LPS); the enzyme activity was 23000U / mg; the purchasing distributor was Shanghai McLean Biochemical Technology Co., Ltd.

[0065] The following examples were all carried out in a macro-micro reactor system, and the macro-micro reactor was as shown in Figure 1 The macro-micro reactor was made: in the macro-micro reactor HSI (D-d4-l3), D represents the inner diameter of the reactor in mm, d4 represents the diameter of the spiral in mm, and l3 represents the pitch in mm. There are four types, macro-micro reactors SLSI (D-d1), SSI (D-d2-l1), and OSI (D-d3-l2). The macro-micro reactor SLSI (D-d1) does not involve the pitch.

[0066] The following examples involve two reactions, namely the combination of enzymatic transesterification and Cu(0) mediated controlled radical polymerization, both reactions are carried out simultaneously, do not affect each other, and the new monomer produced by enzymatic transesterification can be provided for polymerization.

[0067] The transesterification conversion rate catalyzed by the enzyme and the polymerization conversion rate catalyzed by Cu(0) in the following examples are calculated by hydrogen spectrum of quenched reaction solution, and the degree of transesterification and polymerization reaction is calculated by the integral ratio of corresponding characteristic peaks. Specifically, taking Example 1 as an example, the enzyme-catalyzed transesterification conversion rate = n-hexyl acrylate peak integral / (n-hexyl acrylate integral + trifluoroethyl acrylate integral) * 100%; the Cu(0)-catalyzed polymerization conversion rate = (poly-n-hexyl acrylate peak + poly-trifluoroethyl acrylate peak) / (poly-n-hexyl acrylate peak + poly-trifluoroethyl acrylate peak + n-hexyl acrylate peak + trifluoroethyl acrylate peak) * 100%.

[0068] Example 1

[0069] 0.6 g of CALB with a particle size of 0.3-0.9 mm was filled into a macro-micro reactor HSI (4.3-1-3) (retention volume 1.00 mL). The pipeline was flushed with toluene solvent treated by heavy evaporation drying. 9.631 g (62.5 mmol) of trifluoroethyl acrylate, 6.385 g (62.5 mmol) of n-hexanol, 0.061 g (0.3125 mmol) of 2-bromo-2-methylpropionic acid ethyl ester, 0.018 g (0.078 mmol) of tris (2-dimethylaminoethyl) amine and dimethyl sulfoxide (0.14 mL) were added in a 50 mL Schlenk round-bottom flask to form a solution, and the dissolved oxygen in the solvent was removed by Schlenk anhydrous oxygen-free technology. It was moved into a syringe, and the flow rate of the syringe pump was set to 0.01667 mL / min, i.e. the residence time was 60 min. The reaction temperature was 40°C, and the reaction was started. After 120 min, the reaction solution was collected and quenched in liquid nitrogen at the same time. After the collection was completed, 90 mL of cold methanol was added and rested for 2 h, and the precipitate was separated by centrifugation and dissolved in tetrahydrofuran and re-precipitated as described above. The separation and purification step was repeated for a total of three times, and the product was dried in a vacuum drying oven for 48 h. The enzyme-catalyzed transesterification conversion rate was 97.74%, and the Cu(0)-catalyzed polymerization conversion rate was 63.23%. The number average molecular weight of the obtained polytrifluoroethyl acrylate-poly-n-hexyl acrylate copolymer (PTFEA-co-PHA) was 12230 g / mol, the molecular weight distribution index was 1.14, and the yield per minute was 0.0445 g / min. 10 -co-PHA 66 The number average molecular weight of the obtained polytrifluoroethyl acrylate-poly-n-hexyl acrylate copolymer (PTFEA-co-PHA) was 12230 g / mol, the molecular weight distribution index was 1.14, and the yield per minute was 0.0445 g / min. Figure 2

[0070] Example 2

[0071] ​A macro-micro reactor SSI (4.3-1-3) was filled with 0.6 g of CALB having a particle size of 0.3-0.9 mm (retention volume of 1.00 mL). The tubing was flushed with toluene which was dried over sodium sulfate. A 50 mL Schlenk round bottom flask was charged with 10.506 g (62.5 mmol) of trifluoroethyl methacrylate, 10.769 g (62.5 mmol) of undecanol, 0.066 g (0.3125 mmol) of ethylene glycol bromo isobutyrate, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine and N,N-dimethylformamide (4.11 mL) to make a solution, and the dissolved oxygen in the solution was removed using Schlenk anhydrous oxygen-free technique. It was moved into a syringe and the syringe pump was set at a flow rate of 0.0111 mL / min, i.e. a residence time of 90 min. The reaction temperature was 40°C, and the reaction was started, and after 180 min, the reaction solution was collected, and at the same time, it was quenched in liquid nitrogen. After the collection was completed, 90 mL of cold methanol was added and left for 2 h, and the precipitate was separated by centrifugation, and was dissolved using tetrahydrofuran and was re-precipitated as described above. The separation and purification steps were repeated a total of three times, and the product was dried in a vacuum drying oven for 48 h. The conversion of the enzyme catalyzed transesterification was 82.6%, and the conversion of the Cu(0) catalyzed polymerization was 35.82%. The number average molecular weight of the obtained poly(trifluoroethyl methacrylate-co-undecyl methacrylate) (PTFEMA 13 -co-PX 59 ) was 7300 g / mol, the molecular weight distribution index was 1.19, and the production rate per minute was 0.0342 g / min.

[0072] Example 3

[0073] CALB with a particle size of 0.3-0.9 mm was packed into a macro-micro reactor OSI (4.3-1-3) (3.00 mL of hold-up volume). The tubing was flushed with toluene which was dried by distillation. A solution of 6.257 g (62.5 mmol) of methyl methacrylate, 4.633 g (62.5 mmol) of n-butanol, 0.079 g (0.3125 mmol) of diethyl 2-bromo-2-methylmalonate, 0.032 g (0.078 mmol) of 4,4'-dibutyryl-2,2'-bipyridine and tetrahydrofuran (1.15 mL) was prepared in a 50 mL Schlenk round bottom flask and the dissolved oxygen was removed by Schlenk technique. This solution was transferred into a syringe and the syringe pump was set to a flow rate of 0.0333 mL / min, which corresponds to a residence time of 90 min. The reaction temperature was set to 40 °C and the reaction was started. After 180 min the reaction was quenched by collecting the reaction mixture in liquid nitrogen. After the collection was finished, 90 mL of cold methanol was added and the mixture was left for 2 h. The precipitate was separated by centrifugation and dissolved in tetrahydrofuran and re-precipitated as described above. This procedure was repeated three times and the product was dried in a vacuum oven for 48 h. The conversion of the enzymatic transesterification was 26.15% and the conversion of the Cu(0)-catalyzed polymerization was 40.15%. The number average molecular weight of the obtained poly(methyl methacrylate)-co-poly(n-butyl methacrylate) (PMMA-co-PX) was 10570 g / mol, the molecular weight distribution index was 1.31 and the yield per minute was 0.0331 g / min. 61 -co-PX 21 .

[0074] Example 4

[0075] A macro-micro reactor HSI (4.3-1-3) was filled with 0.6 g of CALB having a particle size of 0.3-0.9 mm (retention volume of 1.00 mL). The tubing was flushed with toluene that was treated with azeotropic drying. A 50 mL Schlenk round bottom flask was charged with 4.815 g (31.25 mmol) of trifluoroethyl acrylate, 1.002 g (31.25 mmol) of methanol, 0.061 g (0.3125 mmol) of 2-bromo-2-methylpropionic acid ethyl ester, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine, and dimethyl sulfoxide (1.025 mL) to make a solution, and the dissolved oxygen in the solution was removed using Schlenk anhydrous oxygen-free technique. It was moved into a syringe and set at a flow rate of 0.0333 mL / min, i.e. a residence time of 30 min. The reaction temperature was 40 °C, and the reaction was started, and after 60 min, the reaction solution was collected, and at the same time, it was quenched by putting into liquid nitrogen. After the collection was completed, 90 mL of cold methanol was added and left for 2 h, and the precipitate was separated by centrifugation, and was dissolved using tetrahydrofuran and was re-precipitated as described above. The separation and purification steps were repeated a total of three times, and the product was dried in a vacuum drying oven for 48 h. The conversion of the enzyme catalyzed transesterification was measured to be 97.0%, and the conversion of the Cu(0) catalyzed polymerization was 21.93%. The number average molecular weight of the obtained poly(trifluoroethyl acrylate)-co-poly(methyl acrylate) copolymer structure (PTFEA8-co-PMA 32 ) was 4250 g / mol( Figure 3 ), the molecular weight distribution index was 1.36, and the production rate per minute was 0.0398 g / min.

[0076] Example 5

[0077] Example 1 2.4 g of CALB with a particle size of 0.3-0.9 mm was packed into the macro-micro reactor HSI (8-3-1) (the reserved volume was 4.00 mL). The pipeline was flushed with toluene which was treated by re-evaporation drying. 10.137 g (62.5 mmol) of benzyl acrylate, 2.003 g (62.5 mmol) of methanol, 0.076 g (0.3125 mmol) of ethyl α-bromophenylacetate, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine and dimethyl sulfoxide (3.715 mL) were added into a 50 mL Schlenk round bottom flask to make a solution, and the dissolved oxygen in the solution was removed by Schlenk anhydrous oxygen-free technique. It was moved into a syringe, and the flow rate of the syringe pump was set to 0.13333 mL / min, i.e. the residence time was 30 min. The reaction temperature was 40°C, and the reaction was started. After 60 min, the reaction solution was collected, and at the same time, it was quenched in liquid nitrogen. After the collection was completed, 90 mL of cold methanol was added and left for 2 h, and the precipitate was separated by centrifugation, dissolved with tetrahydrofuran and re-precipitated as described above. The separation and purification steps were repeated a total of three times, and the product was dried in a vacuum drying oven for 48 h. The conversion rate of enzyme catalyzed transesterification was 85.23%, and the conversion rate of Cu(0) catalyzed polymerization was 48.37%. The number average molecular weight of the obtained poly(benzyl acrylate)-poly(methyl acrylate) copolymer (PX 28 -co-PMA 71 ) was 12670 g / mol, the molecular weight distribution index was 1.28, and the production rate per minute was 0.0119 g / min.

[0078] Example 6

[0079] Example 1 3.0 g of CALB with a particle size of 0.3-0.9 mm was packed into the macro-micro reactor HSI (10-3-3) (retention volume 5.00 mL). The tubing was flushed with toluene which had been treated by drying over phosphorus pentoxide. In a 50 mL Schlenk round bottom flask, 5.380 g (62.5 mmol) of methyl acrylate, 6.385 g (62.5 mmol) of n-hexanol, 0.061 g (0.3125 mmol) of 2-bromo-2-methylpropionic acid ethyl ester, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine and dimethyl sulfoxide (2.15 mL) were dissolved and the dissolved oxygen was removed using Schlenk anhydrous oxygen-free technique. This was transferred into a syringe and the syringe pump was set to a flow rate of 0.5 mL / min, i.e. a residence time of 10 min. The reaction temperature was set to 60 °C and the reaction was started. After 20 min the reaction was collected and quenched by immersion in liquid nitrogen. After the collection was complete, 90 mL of cold methanol was added and left to stand for 2 h. The precipitate was separated by centrifugation and dissolved in tetrahydrofuran and re-precipitated as described above. This purification step was repeated three times in total and the product was dried in a vacuum oven for 48 h. The conversion of the enzyme catalysed transesterification was measured to be 47.9% and the conversion of the Cu(0) catalysed polymerisation was 43.29%. The resulting poly(methyl acrylate)-co-poly(n-hexyl acrylate) (PMA-co-PHA) had a number average molecular weight of 11580 g / mol (Mn), a molecular weight distribution index of 1.21 and a yield of 0.0326 g / min. 58 Example 2 26 Example 3 Figure 4 Example 4 Example 5

[0080] Example 6 Example 7

[0081] Example 1 0.6 g of CALB with a particle size of 0.3-0.9 mm was packed into a macro-micro reactor HSI (3-1-10) (retention volume of 1.00 mL). The tubing was flushed with toluene that was treated with azeotropic drying. A solution was prepared in a 50 mL Schlenk round bottom flask by adding 8.01 g (62.5 mmol) of n-butyl acrylate, 7.013 g (62.5 mmol) of t-butyl alcohol, 0.043 g (0.3125 mmol) of 2-chloropropyl ethyl ether, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine, and toluene (4.20 mL) and removing dissolved oxygen from the solvent using Schlenk anhydrous oxygen-free techniques. This was moved to a syringe and the syringe pump was set to a flow rate of 0.01667 mL / min, which is a residence time of 60 min. The reaction temperature was 60 °C and the reaction was started. After 120 min the reaction was collected and quenched by placing in liquid nitrogen. After the collection was complete, 90 mL of cold methanol was added and allowed to sit for 2 h. The precipitate was separated by centrifugation and dissolved in tetrahydrofuran and re-precipitated as described above. This purification step was repeated a total of three times and the product was placed in a vacuum oven to dry for 48 h. The conversion of the enzyme catalyzed transesterification was measured to be 31.25% and the conversion of the Cu(0) catalyzed polymerization was 27.8%. The number average molecular weight of the resulting poly(n-butyl acrylate)-poly(t-butyl acrylate) copolymer (PX 31 -co-PX 24 ) was 7100 g / mol with a molecular weight distribution index of 1.54 and a production rate of 0.0163 g / min.

[0082] Example 8

[0083] Example 1 1.2 g of CALB with a particle size of 0.3-0.9 mm was packed into a macro- microreactor SSI (3-1-8) (retention volume of 2.00 mL). The tubing was flushed with toluene that was dried by distillation. A solution of 9.638 g (62.5 mmol) of cyclohexyl acrylate, 3.756 g (62.5 mmol) of isopropyl alcohol, 0.041 g (0.3125 mmol) of 2-bromopropionitrile, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine and N,N-dimethylformamide (5.18 mL) was prepared in a 50 mL Schlenk round bottom flask and the dissolved oxygen was removed by Schlenk anhydrous oxygen-free technique. It was transferred into a syringe and the syringe pump was set at a flow rate of 0.013333 mL / min, i.e. a residence time of 150 min. The reaction temperature was 0 °C and the reaction was started. After 300 min the reaction was collected and quenched by immersion in liquid nitrogen. After the collection was completed, 90 mL of cold methanol was added and left for 2 h. The precipitate was separated by centrifugation and dissolved in tetrahydrofuran and re-precipitated as described above. The purification steps were repeated three times and the product was dried in a vacuum oven for 48 h. The conversion of the enzymatic transesterification was 9.39% and the conversion of the Cu(0)-catalyzed polymerization was 56.79%. The number average molecular weight of the obtained cyclohexyl acrylate-isopropyl acrylate copolymer (PX 103 -co-PX 12 ) was 12950 g / mol, the molecular weight distribution index was 1.32 and the production rate was 0.0243 g / min.

[0084] Example 9

[0085] A macro-micro reactor HSI (4.3-1-3) was filled with 0.6 g of CALB having a particle size of 0.3-0.9 mm (retention volume of 1.00 mL). The tubing was flushed with toluene which was dried over sodium sulfate. A 50 mL Schlenk round bottom flask was charged with 9.631 g (62.5 mmol) of trifluoroethyl acrylate, 6.385 g (62.5 mmol) of n-hexanol, 0.061 g (0.3125 mmol) of 2-bromo-2-methylpropionic acid ethyl ester, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine and dimethyl sulfoxide (15.49 mL) to make a solution, and the dissolved oxygen in the solution was removed using Schlenk anhydrous oxygen-free technique. It was moved into a syringe and the syringe pump was set at a flow rate of 0.0067 mL / min, i.e. a residence time of 150 min. The reaction temperature was 40 °C, and the reaction was started, and after 300 min the reaction solution was collected and quenched in liquid nitrogen at the same time. After the collection was completed, 90 mL of cold methanol was added and allowed to stand for 2 h, and the precipitate was separated by centrifugation, dissolved with tetrahydrofuran and re-precipitated as described above. The separation and purification steps were repeated a total of three times, and the product was dried in a vacuum drying oven for 48 h. The conversion of the enzyme catalyzed transesterification was measured to be 12.67%, and the conversion of the Cu(0) catalyzed polymerization was 35.54%. The number average molecular weight of the obtained poly(trifluoroethyl acrylate)-co-poly(n-hexyl acrylate) copolymer (PTFEA-co-PHA9) was 12950 g / mol, the molecular weight distribution index was 1.20, and the production rate per minute was 0.0431 g / min. 63

[0086] Example 10

[0087] ​CALB with particle size of 0.3-0.9 mm was packed into the macro-micro reactor OSI (15-2-3) (the reserved volume was 5.00 mL). The pipeline was flushed with toluene which was treated by re-evaporation drying. In a 50 mL Schlenk round bottom flask, 4.005 g (31.25 mmol) of n-butyl acrylate, 5.131 g (31.25 mmol) of triethylene glycol monomethyl ether, 0.059 g (0.3125 mmol) of 2,2-dichloroacetophenone, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine and dimethyl sulfoxide (0.94 mL) were dissolved to make a solution, and the dissolved oxygen in the solution was removed by Schlenk anhydrous oxygen-free technique. It was moved into a syringe, and the flow rate of the syringe pump was set to 0.16667 mL / min, i.e. the residence time was 30 min. The reaction temperature was 40°C, and the reaction was started. After 60 min, the reaction solution was collected, and at the same time, it was quenched in liquid nitrogen. After the collection was completed, 90 mL of cold methanol was added and left for 2 h, and the precipitate was separated by centrifugation, dissolved with tetrahydrofuran and re-precipitated as described above. The separation and purification steps were repeated a total of three times, and the product was dried in a vacuum drying oven for 48 h. The conversion rate of enzyme catalyzed transesterification was 7.87%, and the conversion rate of Cu(0) catalyzed polymerization was 38.10%. The number average molecular weight of the obtained poly(n-butyl acrylate)-poly(triethylene glycol monomethyl ether acrylate) copolymer (PX 65 -co-PX2) was 8010 g / mol, the molecular weight distribution index was 1.69, and the production rate per minute was 0.0751 g / min.

[0088] Example 11

[0089] Example 1 0.6 g of CALB with a particle size of 0.3-0.9 mm was packed into a macro-micro reactor OSI (2-0.5-5) (retention volume of 1.00 mL). The tubing was flushed with toluene that was treated with azeotropic drying. A solution was prepared in a 50 mL Schlenk round bottom flask by adding 9.638 g (62.5 mmol) of cyclohexyl acrylate, 6.125 g (62.5 mmol) of furfuryl alcohol, 0.038 g (0.3125 mmol) of methyl 2-chloropropionate, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine, and dimethyl sulfoxide (0.325 mL) and the dissolved oxygen in the solvent was removed using Schlenk anhydrous oxygen-free technique. It was moved into a syringe and the syringe pump was set at a flow rate of 0.00833 mL / min, i.e. a residence time of 120 min. The reaction temperature was 40 °C and the reaction was started. After 240 min, the reaction was collected and quenched in liquid nitrogen. After the collection was completed, 90 mL of cold methanol was added and allowed to stand for 2 h. The precipitate was separated by centrifugation and dissolved using tetrahydrofuran and re-precipitated as described above. The purification steps were repeated three times in total and the product was dried in a vacuum drying oven for 48 h. The conversion of the enzyme catalyzed transesterification was measured to be 75.23% and the conversion of the Cu(0) catalyzed polymerization was 21.83%. The number average molecular weight of the obtained cyclohexyl acrylate-furfuryl acrylate copolymer (PX 17 -co-PX 40 ) was 9530 g / mol, the molecular weight distribution index was 1.35 and the production rate per minute was 0.0239 g / min.

[0090] Example 12

[0091] Example 1 1 1.8 g of CALB with a particle size of 0.3-0.9 mm was packed into a macro-micro reactor HSI (6-0.5-10) (retention volume 3.00 mL) and the tubing was flushed with toluene which was dried by repeated evaporation. In a 50 mL Schlenk round bottom flask, 9.632 g (62.5 mmol) of trifluoroethyl acrylate, 8.19 g (62.5 mmol) of 2-morpholinoethanol, 0.061 g (0.3125 mmol) of ethyl 2-bromo-2-methylpropionate, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine and dimethyl sulfoxide (0.135 mL) were dissolved and the dissolved oxygen was removed by Schlenk anhydrous and anaerobic technique. It was moved into a syringe and the syringe pump was set at a flow rate of 0.05 mL / min, i.e. a residence time of 60 min. The reaction temperature was 40 °C and the reaction was started. After 120 min, the reaction was collected and quenched by placing it in liquid nitrogen. After the collection was completed, 90 mL of cold methanol was added and left for 2 h. The precipitate was separated by centrifugation and dissolved in tetrahydrofuran and re-precipitated as described above. The purification step was repeated three times in total and the product was dried in a vacuum drying oven for 48 h. The conversion of the enzyme catalyzed transesterification was 92.53% and the conversion of the Cu(0) catalyzed polymerization was 58.03%. The number average molecular weight of the obtained poly(trifluoroethyl acrylate)-co-poly(morpholinoethyl acrylate) (PTFEA-co-PX) was 19530 g / mol (Mn), the molecular weight distribution index was 1.21 and the yield per minute was 0.0915 g / min. 23 -co-PX 95 ) of 19530 g / mol (Mn), the molecular weight distribution index of 1.21 and the yield per minute of 0.0915 g / min. Figure 5

[0092] Example 13

[0093] ​0.6 g of CALB with a particle size of 0.3–0.9 mm was packed into the macro-microreactor HSI (4.3-1-3) (retention volume 1.00 mL). The tubing was flushed with toluene solvent that had been redistilled and dried. A solution was prepared in a 50 mL Schlenk round-bottom flask by adding 9.631 g (62.5 mmol) of trifluoroethyl acrylate, 6.385 g (62.5 mmol) of n-hexanol, 0.061 g (0.3125 mmol) of ethyl 2-bromo-2-methylpropionate, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine, and dimethyl sulfoxide (6.56 mL). Dissolved oxygen in the solvent was removed using the Schlenk anhydrous and oxygen-free technique. The solution was then transferred into a syringe, and the flow rate of the syringe pump was set to 0.0111 mL / min, i.e., a residence time of 90 min. The reaction was initiated at 40℃, and the reaction solution was collected after 180 min, simultaneously quenched in liquid nitrogen. After collection, 90 mL of cold methanol was added, and the mixture was allowed to stand for 2 h. The precipitate was then separated by centrifugation, dissolved in tetrahydrofuran, and separated again according to the above method. The separation and purification steps were repeated three times, and the product was dried in a vacuum drying oven for 48 h. The enzyme-catalyzed transesterification conversion rate was measured to be 23.07%, and the Cu(O)-catalyzed polymerization conversion rate was 61.06%. The obtained poly(trifluoroethyl acrylate)-poly(n-hexyl acrylate) copolymer (PTFEA) 55 -co-PHA 45 The number-average molecular weight was 16640 g / mol, the molecular weight distribution index was 1.23, and the yield per minute was 0.0708 g / min.

[0094] Example 14

[0095] CALB with a particle size of 0.3-0.9 mm was packed into the macro-micro reactor SLSI (4.3-1) (retention volume 1.00 mL). The tubing was flushed with toluene which was dried over sodium sulfate. A solution of 5.380 g (62.5 mmol) methyl acrylate, 10.769 g (62.5 mmol) undecanol, 0.061 g (0.3125 mmol) ethyl 2-bromo-2-methylpropanoate, 0.018 g (0.078 mmol) tris(2-dimethylaminoethyl)amine and dimethyl sulfoxide (2.0 mL) was prepared in a 50 mL Schlenk round bottom flask and the dissolved oxygen was removed using Schlenk anhydrous oxygen-free technique. This was transferred into a syringe and the syringe pump was set to a flow rate of 0.01667 mL / min, i.e. a residence time of 60 min. The reaction temperature was set to 40 °C and the reaction was started. After 120 min the reaction was collected and quenched by immersion in liquid nitrogen. After the collection was complete, 90 mL of cold methanol was added and left to stand for 2 h. The precipitate was separated by centrifugation and dissolved in tetrahydrofuran and re-precipitated as described above. This purification step was repeated three times in total and the product was dried in a vacuum oven for 48 h. The conversion of the enzymatic transesterification was measured to be 63.20% and the conversion of the Cu(0) catalysed polymerisation was 35.61%. The number average molecular weight of the poly(methyl acrylate)-co-poly(undecyl acrylate) copolymer (PMA 40 -co-PX 32 ) was 9640 g / mol (Mn) with a molecular weight distribution index of 1.22 and a yield of 0.0471 g / min. Figure 6

[0096] Example 15

[0097] ​Example 1 1 1.1 g of CALB with a particle size of 0.3-0.9 mm was packed into the macro-microreactor HSI (4.3-1-3) (retention volume 2.00 mL). The tubing was flushed with toluene which was dried over sodium sulfate. A solution of 9.631 g (62.5 mmol) of trifluoroethyl acrylate, 4.442 g (62.5 mmol) of 3-hydroxypropionitrile, 0.061 g (0.3125 mmol) of ethyl 2-bromo-2-methylpropionate, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine and dimethyl sulfoxide (3.435 mL) was prepared in a 50 mL Schlenk round bottom flask and the dissolved oxygen was removed from the solvent using Schlenk anhydrous oxygen-free technique. This was transferred into a syringe and the syringe pump was set to a flow rate of 0.0222 mL / min, i.e. a residence time of 90 min. The reaction temperature was set to 40 °C and the reaction was started. After 180 min the reaction was collected and quenched in liquid nitrogen. After the collection was complete, 90 mL of cold methanol was added and left to stand for 2 h. The precipitate was separated by centrifugation and dissolved in tetrahydrofuran and re-precipitated as described above. This purification step was repeated three times in total and the product was dried in a vacuum oven for 48 h. The conversion of the enzymatic transesterification was 86.32% and the conversion of the Cu(0)-catalyzed polymerization was 42.33%. The number average molecular weight of the obtained poly(trifluoroethyl acrylate-co- polypropionitrile) (PTFEA-co-PX) was 14740 g / mol (Mn) with a molecular weight distribution index of 1.27 and a yield of 0.0506 g / min. 24 -co-PX 67 . Figure 7

[0098] Example 16

[0099] ​A 1 mm diameter stainless steel wire was used as the central axis, and a 3 mm pitch was used as the standard. A 1 mm diameter copper wire was uniformly and tightly wound around the central axis to make a copper spiral inner member. The inner member was placed in a microchannel with an inner diameter of 4.3 mm, and the activation operation was performed. 0.6 g of immobilized enzyme Novozyme435 with a particle size of 0.3-0.9 mm was filled into the activated copper spiral inner member microreactor (retention volume 1.00 mL), and a small amount of cotton was used to fix the two end ports. A 1 mm inner diameter microchannel tube was used to connect the syringe and the new microreactor (retention volume 0.5 mL), and a 1 mm inner diameter microchannel reactor was used to connect the new microreactor and the receiving device (retention volume 0.5 mL). The solvent was flushed with toluene after being dried by re-evaporation. In a 50 mL Schlenk round-bottom flask, 62.5 mmol (9.631 g) of trifluoroethyl acrylate (7.92 mL), 62.5 mmol (2.003 g) of methanol (2.53 mL), 0.3125 mmol (0.061 g) of 2-bromo-2-methylpropyl acetate, 0.078 mmol (0.018 g) of tris(2-dimethylaminoethyl)amine, and dimethyl sulfoxide (2.05 mL) were dissolved, and the dissolved oxygen in the solvent was removed by bubbling. It was moved into the sample injection syringe, the flow rate was set to 0.01111 mL / min, the reaction temperature was set to 0°C, the reaction was started, and after 90 min, the reaction liquid was collected, and at the same time, it was put into liquid nitrogen for quenching. After the collection was completed, 90 mL of cold methanol was added and left for 2 h, the precipitate was separated by centrifugation, and was dissolved in tetrahydrofuran and re-precipitated as described above. The separation and purification step was repeated a total of three times, and the product was placed in a vacuum drying oven for 48 h. The structure of the obtained poly(trifluoroethyl acrylate)-poly(methyl acrylate) copolymer was identified by 1 HNMR and GPC identification showed that the enzyme catalyzed ester exchange conversion rate was 97.74%, and the Cu(0) catalyzed polymerization conversion rate was 58.01%. The number average molecular weight of the polymer was 12400 g / mol, and the molecular weight distribution index was 1.21, as determined by GPC.

[0100] Comparative Example 1

[0101] In a 50 mL Schlenk round bottom flask, 9.631 g (62.5 mmol) of trifluoroethyl acrylate, 6.385 g (62.5 mmol) of n-hexanol, 0.061 g (0.3125 mmol) of 2-bromo-2-methylpropionic acid ethyl ester, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine, 40 mg of copper powder, 0.6 g of Novozyme immobilized lipase, and dimethyl sulfoxide (0.135 mL) were dissolved to make a solution, and dissolved oxygen in the solvent was removed using Schlenk anhydrous oxygen-free technology. The reaction temperature was 40°C, and the reaction was started. After 60 min, the reaction was quenched in liquid nitrogen. At the same time, 90 mL of cold methanol was added and left for 2 h, and the precipitate was separated by centrifugation. The precipitate was dissolved in tetrahydrofuran and re-precipitated as described above. The purification step was repeated three times in total, and the product was dried in a vacuum drying oven for 48 h. The conversion rate of the enzyme-catalyzed transesterification was 74.97%, and the conversion rate of the Cu(0)-catalyzed polymerization was 23.08%. The number average molecular weight of the obtained poly(trifluoroethyl acrylate)-poly(n-hexyl acrylate) copolymer (PTFEA 15 -co-PHA 32 ) was 8160 g / mol, and the molecular weight distribution index was 1.42.

[0102] Comparative Example 2

[0103] The immobilized enzyme Novozyme 435 with particle size of 0.3-0.9 mm and weight of 0.6 g was filled into a copper tube microreactor with inner diameter of 1 mm (retention volume 1.00 mL) which was activated. The tube was flushed with toluene which was dried by distillation. A solution of 9.632 g (62.5 mmol) of trifluoroethyl acrylate, 6.385 g (62.5 mmol) of n-hexanol, 0.061 g (0.3125 mmol) of 2-bromo-2-methylpropionic acid ethyl ester, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine and dimethyl sulfoxide (0.135 mL) was prepared in a 50 mL Schlenk round bottom flask and the dissolved oxygen in the solution was removed by Schlenk anhydrous and anaerobic technique. The solution was moved into a syringe and the flow rate of the syringe pump was set to 0.01667 mL / min and the reaction temperature was set to 40 °C. The reaction was started, but the tube was blocked and the syringe pump was alarmed due to the high flow rate. The flow rate was then changed to 0.00667 mL / min, i.e. the residence time was 150 min. The reaction solution was collected after 300 min and was quenched by liquid nitrogen at the same time. After the collection was finished, 90 mL of cold methanol was added and the mixture was left for 2 h. The precipitate was separated by centrifugation and was dissolved in tetrahydrofuran and precipitated again as described above. The separation and purification steps were repeated three times and the product was dried in a vacuum drying oven for 48 h. The conversion of the enzyme catalyzed transesterification was 89.39% and the conversion of the Cu(0) catalyzed polymerization was 46.02%. The number average molecular weight of the obtained poly(trifluoroethyl acrylate)-co-poly(n-hexyl acrylate) (PTFEA-co-PHA) was 15570 g / mol, the molecular weight distribution index was 1.15 and the production rate was 0.0292 g / min. 25 -co-PHA 70 .

[0104] Comparative Example 3

[0105] A 0.6 g of immobilized enzyme Novozyme 435 with particle size of 0.3-0.9 mm was packed into a copper tube continuous flow microreactor (retention volume 1.00 mL) with inner diameter of 4.3 mm. The tube was flushed with toluene solvent which was dried by distillation. A solution of 9.632 g (62.5 mmol) of trifluoroethyl acrylate, 6.385 g (62.5 mmol) of n-hexanol, 0.061 g (0.3125 mmol) of ethyl 2-bromo-2-methylpropionate, 0.018 g (0.078 mmol) of tris(2-dimethylaminoethyl)amine and dimethyl sulfoxide (0.135 mL) was prepared in a 50 mL Schlenk round bottom flask and the dissolved oxygen in the solution was removed by Schlenk anhydrous oxygen-free technique. The solution was transferred into a syringe and the syringe pump was set at a flow rate of 0.016667 mL / min, i.e. a residence time of 60 min. The reaction temperature was set at 40 °C and the reaction was started. After 120 min, the reaction solution was collected and quenched by liquid nitrogen. After the collection was completed, 90 mL of cold methanol was added and the mixture was allowed to stand for 2 h. The precipitate was separated by centrifugation and dissolved in tetrahydrofuran and re-precipitated as described above. The purification steps were repeated three times and the product was dried in a vacuum drying oven for 48 h. The conversion of the enzyme catalyzed transesterification was 81.05% and the conversion of the Cu(0) catalyzed polymerization was 44.79%. The number average molecular weight of the obtained poly(trifluoroethyl acrylate)-co-poly(n-hexyl acrylate) (PTFEA-co-PHA) was 12950 g / mol, the molecular weight distribution index was 1.22 and the yield per minute was 0.0404 g / min. 15 -co-PHA 71 .

[0106] Comparative Example 4

[0107] The 3.0 g immobilized enzyme Novozyme 435 with particle size of 0.3-0.9 mm was filled into the activated copper tube microreactor with inner diameter of 6 mm (retention volume 5.00 mL), and the tube ports at both ends were fixed with a small amount of cotton. The microchannel tube with inner diameter of 1 mm was used to connect the syringe and the new microreactor (retention volume 0.5 mL), and the microchannel reactor with inner diameter of 1 mm was used to connect the new microreactor and the receiving device (retention volume 0.5 mL). The toluene solvent treated by heavy evaporation drying was used to flush the pipeline. 62.5 mmol (10.137 g) of benzyl acrylate, 62.5 mmol (6.125 g) of furfuryl alcohol, 0.3125 mmol (0.061 g) of 2-bromo-2-methylpropionic acid ethyl ester, 0.078 mmol (0.018 g) of tris (2-dimethylaminoethyl) amine and dimethyl sulfoxide (2.05 mL) were added in a 50 mL Schlenk round-bottom flask to form a solution, and the dissolved oxygen in the solvent was removed by bubbling. It was moved into the sample injection syringe, and the flow rate was set to 0.083 mL / min, i.e. the residence time was 60 min. The reaction temperature was 60°C, and the reaction was started. After 120 min, the reaction solution was collected, and at the same time, it was quenched in liquid nitrogen. After the collection was completed, 90 mL of cold methanol was added and left for 2 h, and the precipitate was separated by centrifugation, dissolved with tetrahydrofuran and re-separated by the above-mentioned precipitation separation. The separation and purification step was repeated for a total of three times, and the product was placed in a vacuum drying box for drying for 48 h. The structure of the obtained benzyl acrylate-furfuryl acrylate copolymer was identified by 1 HNMR and GPC identification showed that the enzyme catalyzed ester exchange conversion rate was 6.07%, and the Cu(0) catalyzed polymerization conversion rate was 48.44%. The number average molecular weight of the polymer was 7190 g / mol, and the molecular weight distribution index was 1.14, which was determined by GPC.

[0108] The above-described embodiments only express several embodiments of the present application, which are described in a more specific and detailed manner, but cannot be understood as limiting the scope of the patent of the present application. It should be noted that for ordinary skilled persons in the art, several modifications and improvements can be made without departing from the concept of the present application, which all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims.

Claims

1. A method for preparing functionalized polymers using a continuous flow chemical-enzymatic process, characterized in that, A mixture of (meth)acrylate monomers, initiators, ligands, functional alcohols and solvents is reacted in a macro-microreactor to obtain a reaction solution containing functionalized polyacrylates. The method for preparing the macro-micro reactor is as follows: A copper spiral with a hollow center and an immobilized enzyme are placed inside a microchannel tube with an inner diameter of 2-4.3 mm; wherein the retention volume of the macro-microreactor is 1-3 mL; the diameter of the copper spiral is 0.5-1 mm and the pitch is 1-3 mm; the immobilized enzyme is an immobilized lipase. or, The hollowed-out copper internal component and the immobilized enzyme are placed inside a microchannel tube with an inner diameter of 2-15 mm; wherein the retention volume of the macro-microreactor is 1-20 mL; the diameter of the copper internal component is 0.5-3 mm; the copper internal component is a spiral-shaped copper internal component, a serpentine copper internal component, or an O-shaped copper internal component.

2. The application of a macro-microreactor in the preparation of functionalized polymers, characterized in that, A mixture of (meth)acrylate monomers, initiators, ligands, functional alcohols and solvents is reacted in a macro-microreactor to obtain a reaction solution containing functionalized polyacrylates. The method for preparing the macro-micro reactor is as follows: A copper spiral with a hollow center and an immobilized enzyme are placed inside a microchannel tube with an inner diameter of 2-4.3 mm; wherein the retention volume of the macro-microreactor is 1-3 mL; the diameter of the copper spiral is 0.5-1 mm and the pitch is 1-3 mm; the immobilized enzyme is an immobilized lipase. or, The hollowed-out copper internal component and the immobilized enzyme are placed inside a microchannel tube with an inner diameter of 2-15 mm; wherein the retention volume of the macro-microreactor is 1-20 mL; the diameter of the copper internal component is 0.5-3 mm; the copper internal component is a spiral-shaped copper internal component, a serpentine copper internal component, or an O-shaped copper internal component.

3. The method according to claim 1 or the application according to claim 2, characterized in that, The (meth)acrylate monomers include methacrylate monomers; the methacrylate monomers include trifluoroethyl methacrylate, methyl methacrylate, or any combination thereof.

4. The method according to claim 1 or the application according to claim 2, characterized in that, The initiator includes ethyl 2-chloropropionate, 2-bromopropionitrile, 2,2-dichloroacetophenone, methyl 2-chloropropionate, or any combination thereof.

5. The method according to claim 1 or the application according to claim 2, characterized in that, The functional alcohols include n-propanol, isopropanol, triethylene glycol monomethyl ether, 3-hydroxypropionitrile, or any combination thereof.

6. The method according to claim 1 or the application according to claim 2, characterized in that, The (meth)acrylate monomers are any one or a combination of several of the following: trifluoroethyl acrylate, methyl acrylate, n-butyl acrylate, benzyl acrylate, and cyclohexyl acrylate.

7. The method according to claim 1 or the application according to claim 2, characterized in that, The initiator is any one or a combination of several of ethyl 2-bromo-2-methylpropionate, ethyl α-bromophenylacetate, diethyl 2-bromo-2-methylmalonate, and ethylene glycol bromoisobutyrate; the molar ratio of the initiator to the (meth)acrylate monomer is 1:100~1000.

8. The method according to claim 1 or the application according to claim 2, characterized in that, The ligand is tris(2-dimethylaminoethyl)amine and / or 4,4'-dinonyl-2,2'-bipyridine; the molar ratio of the initiator to the ligand is 1:0.1~1.

9. The method according to claim 1 or the application according to claim 2, characterized in that, The functional alcohol is any one or a combination of several of methanol, n-butanol, tert-butanol, n-hexanol, furfuryl alcohol, undecyl alcohol, and 2-morpholine ethanol; the molar ratio of the initiator to the functional alcohol is 1:100~1200.

10. The method according to claim 1 or the application according to claim 2, characterized in that, The solvent is any one or a combination of several of dimethyl sulfoxide, tetrahydrofuran, N,N-dimethylformamide and toluene; the concentration of the (meth)acrylate monomer is 1~5 mol / L.

11. The method according to claim 1 or the application according to claim 2, characterized in that, The immobilized enzyme is an immobilized Novozymes 435 lipase.

12. The method according to claim 1 or the application according to claim 2, characterized in that, The spiral-shaped, serpentine, and O-shaped copper internal components have a pitch of 0.5–10 mm; the immobilized enzyme is Candida antarcticis lipase B. Candida antarctic Lipase B, porcine pancreatic lipase, and Candida albicans lipase Candida rugosa Amano lipase Pseudomonas fluorescens Burkholderia cepacia lipase PS from Burkholderia cepacia Any one or more combinations thereof.

13. The method according to claim 1 or the application according to claim 2, characterized in that, The mixed solution is reacted after dissolved oxygen is removed.

14. The method or application according to claim 13, characterized in that, The method for removing dissolved oxygen is either bubbling or liquid nitrogen freezing-vacuuming-dissolution.

15. The method according to claim 1 or the application according to claim 2, characterized in that, The reaction temperature is 0~100 ℃; the reaction rate is 0.0067~0.5 mL / min; and the reaction retention time is 10~300 min.

16. The method according to claim 1 or the application according to claim 2, characterized in that, The retention time for the reaction is 10 to 150 minutes.

17. The method according to claim 1 or the application according to claim 2, characterized in that, After the reaction is completed, the reaction solution is quenched, an organic precipitant is added, and the mixture is centrifuged to obtain solid functionalized polyacrylate.

18. The method or application according to claim 17, characterized in that, The quenching agent is liquid nitrogen; the organic precipitant is a mixed solution of methanol and water, methanol, or n-hexane.

19. The method according to claim 1 or the application according to claim 2, characterized in that, The flow rate of the reaction is 0.0033~25 mL / min.

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