Method for enzymatic synthesis of biodegradable material in macro-micro reactor

Abstract

The invention discloses a method for enzymatic synthesis of a biodegradable material in a macro-micro reactor, which is characterized in that in the macro-micro reactor, a cyclic monomer, an initiator, a catalyst and a solvent react to obtain degradable polyester. Compared with a traditional synthesis method, the macro-micro reactor containing the internal component can remarkably improve the mass transfer and heat transfer efficiency, shorten the enzymatic ring-opening polymerization reaction time, improve the conversion rate and reduce the molecular weight distribution index. The characteristic scale of the macro-micro reactor reaches centimeter level, and high-flux synthesis can be realized. The invention provides a technical scheme for preparation of the degradable polyester, and has a wide application prospect in industrial chemical manufacturing.

Description

Technical Field

[0001] The invention relates to the technical field of polymer synthesis, and in particular to a method for enzymatically synthesizing biodegradable materials in a macro-microreactor, namely a method for preparing degradable polyester based on enzyme-catalyzed ring-opening polymerization in a macro-microreactor. Background Art

[0002] This section merely provides background information related to the present disclosure and is not necessarily prior art.

[0003] Degradable polyester has excellent mechanical properties, biodegradability and biocompatibility, and has many potential applications in environmental protection, textiles, agriculture, biomedicine and other fields. The synthesis methods of degradable polyester mainly include: 1) polycondensation of dibasic acid and diol, which is usually carried out at high temperature, has a long reaction time and is accompanied by side reactions, resulting in a small number average molecular weight of the polymer; 2) ring-opening polymerization (ROP) of cyclic monomers, which has relatively mild reaction conditions and can synthesize high molecular weight polymers in a relatively short time.

[0004] With the strengthening of people's environmental awareness, the development of green chemistry, and the demand for non-toxic, metal-free, biodegradable polyesters in the fields of biomedicine, enzymatic ring-opening polymerization (eROP) has been studied in depth. Enzymes are highly efficient biocatalysts, and the use of enzymes avoids the metal toxicity that may be caused by metal catalysts. Enzymatic ring-opening polymerization is not limited by the decrease in ring tension as the size of the lactone increases. In contrast to chemical ring-opening polymerization, the larger the lactone ring size, the faster the enzymatic ring-opening polymerization reaction rate.

[0005] Kettle reactors are widely used in industrial reaction processes such as petrochemicals, pesticides, dyes, and pharmaceuticals, but they have disadvantages such as low mass transfer and heat transfer efficiency, cumbersome operating steps, and difficulty in achieving precise control. Microreactors are increasingly valued in the field of polymer synthesis due to their high mass transfer and heat transfer efficiency, good mixing performance, and good spatiotemporal controllability. However, typical microreactors have slow flow rates and low fluxes, and when the viscosity of the reaction solution is high, the pipeline is easily blocked. Although the continuous flow reactor has a large liquid carrying capacity, it loses the microscale effect, resulting in low monomer conversion and difficulty in obtaining high-quality chemical products with a small molecular weight distribution index. The present invention is based on macro-microreactors to carry out enzymatic ring-opening polymerization, shorten the enzymatic ring-opening polymerization time, and improve the conversion rate. The characteristic scale of the macro-microreactor reaches the centimeter level, which can achieve high-throughput synthesis and is of great significance for the preparation of degradable polyesters. Summary of the invention

[0006] Purpose of the invention: The technical problem to be solved by the present invention is to provide a method for enzymatically synthesizing biodegradable materials in macro-microreactors in view of the deficiencies in the prior art.

[0007] Inventive concept: The present invention provides a method for preparing degradable polyester based on enzyme-catalyzed ring-opening polymerization in an internal component macro-microreactor, wherein a cyclic monomer is a ring-opening polymerization monomer, a variety of alcohols are used as initiators, and lipase is used as a catalyst to catalyze the ring-opening polymerization to prepare the degradable polyester, so as to solve the problems of low flux, low conversion rate, long reaction time, and wide polymer molecular weight distribution in the prior art.

[0008] In order to solve the above technical problems, the present invention discloses the following technical solutions:

[0009] In a first aspect, the present invention discloses an application of a macro-micro reactor in the preparation of degradable polyester.

[0010] The application is to prepare degradable polyester using cyclic monomers as raw materials, and in a macro-micro reactor, the cyclic monomers, initiators, catalysts, and solvents are reacted to obtain the degradable polyester.

[0011] In a second aspect, the present invention discloses a method for preparing degradable polyester based on macro-microreactor ring-opening polyester.

[0012] The method for preparing degradable polyester based on macro-microreactor ring-opening polyester is to place cyclic monomers, initiators, catalysts, and solvents in macro-microreactors to obtain degradable polyester.

[0013] The first and second aspects above,

[0014] The monomer is (1a) ε-caprolactone, (1b) δ-valerolactone, (1c) trimethylene carbonate, (1d) ω-pentadecacyclic lactone, (1e) cyclohexanediol, (1f) (Z)-oxocycloheptadeca-8-ene-2-one, or a combination of any of the foregoing, such as a combination of any two of the foregoing.

[0015]

[0016] Wherein, the initiator is an alcohol, and the alcohol includes (2a) benzyl alcohol, (2b) 6-mercapto-1-hexanol, (2c) 5-hexen-1-ol, (2d) N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide, (2e) 3-thiophene methanol, (2f) pyridine-3-methanol, 3-butyn-1-ol, 6-bromo-1-hexanol, and phenylpropanol.

[0017]

[0018] Wherein, the solvent of the reaction is tetrahydrofuran, toluene, dichloromethane, n-hexane, etc., preferably toluene.

[0019] Wherein, the catalyst is an enzyme filled in a macro-microreactor, and the enzyme includes Candida antartica lipase B (CALB or N435), Porcine pancreatic lipase (Porcine pancreaticlipase (PPL)), Amano lipase (Amano Lipase from Pseudomonas fluorescens), Burkholderia cepacia enzyme (lipase PS from Burkholderia cepacia (LPS)), Pseudomonas fluorescens lipase (Pseudomonas fluorescens lipase (PF)), Candida plicata lipase (Lipase from Candidarugosa (CRL), preferably immobilized Candida antarctica enzyme (Novozyme 435).

[0020] Wherein, the molar ratio of the monomer to the initiator is 10-300:1, such as 10:1, 20:1, 150:1, 170:1; the molar mass ratio of the monomer to the catalyst is 0.5-200:1, such as 10:1, 20:1, 150:1, 170:1.

[0021] Wherein, the monomer concentration is 0.1-4 mol / L, preferably 2 mol / L.

[0022] Wherein, the flow rate of the reaction is 0.2-10 mL / min, preferably 5 mL / min.

[0023] Wherein, the macro-microreactor comprises an outer shell and an internal component; preferably, the outer shell is a polytetrafluoroethylene (PFA) tube; preferably, the retention volume of the macro-microreactor is 1-30mL; preferably, the inner diameter of the macro-microreactor is 1-10mm, and the diameter of the internal component is 0.5-3mm.

[0024] Wherein, the internal component is a linear internal component, a spiral internal component, a serpentine internal structure, or an O-shaped internal component. The linear internal component does not have a pitch, the spiral internal component, the serpentine internal structure and the O-shaped internal component have a pitch, and the pitch of the internal component is 1-10mm; for example, in a macro-micro reactor containing a spiral internal component, the inner diameter of the macro-micro reactor is 1-10mm, the diameter of the spiral internal component is 0.5-3mm, and the pitch is 1-10mm. In some preferred embodiments, a macro-micro reactor containing a spiral internal component is selected.

[0025] Wherein, the reaction is carried out in an anhydrous and oxygen-free inert environment.

[0026] Wherein, the reaction temperature is 0-90°C, such as 25°C, 60°C, 90°C, preferably 60°C.

[0027] Specifically,

[0028] When preparing homopolymer degradable polyester, the method specifically comprises: dissolving cyclic monomer and initiator in solvent to prepare homogeneous solution; pumping the obtained homogeneous solution into macro-micro reactor containing enzyme to react and obtain solution containing homopolymer degradable polyester.

[0029] When preparing copolymer degradable polyester, the method specifically includes: dissolving the first cyclic monomer and the initiator in a solvent to prepare a first homogeneous solution; dissolving the second cyclic monomer in a solvent to prepare a second homogeneous solution; pumping the first homogeneous solution into a first macro-micro reactor containing an enzyme to carry out a first reaction, and the resulting effluent and the second homogeneous solution are simultaneously pumped into a second macro-micro reactor containing an enzyme to carry out a second reaction, thereby obtaining a solution containing copolymer degradable polyester. Wherein, the first cyclic monomer and the second cyclic monomer are different, and are independently selected from ε-caprolactone, δ-valerolactone, trimethylene carbonate, pentadecanoic acid cyclohexylene ester, (Z)-oxocycloheptadec-8-ene-2-one.

[0030] After the reaction is completed, an organic solvent is added for precipitation, and centrifugal separation is performed to obtain the degradable polyester.

[0031] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0032] (1) The present invention is based on macro-microreactors to enhance the enzyme-catalyzed ring-opening polymerization process, and quickly and high-throughput prepares a series of degradable polyesters.

[0033] (2) Compared with the traditional tank reactor, the present invention significantly shortens the reaction time and improves the conversion rate based on the macro-micro reactor. For example, using Novozyme 435 to catalyze N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide to initiate the ring-opening polymerization of δ-valerolactone, the reaction time is shortened from 8 h (water bath) to 4 min (macro-micro reactor), and the conversion rate can reach 94%.

[0034] (3) Compared with a typical microreactor (characteristic scale = 1.0 mm), the present invention significantly increases the reaction flux based on the macro-microreactor, for example, the flow rate is increased from 0.15 mL / min (microreactor) to 5 mL / min (macro-microreactor), and the output per unit time is increased from 0.026 g / min (microreactor) to 0.957 g / min (macro-microreactor).

[0035] (4) Compared with a continuous flow reactor (characteristic dimension>2.0 mm, no internal components), the present invention significantly shortens the reaction time and improves the conversion rate based on the macro-micro reactor. For example, using Novozyme 435 to catalyze N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide to initiate the ring-opening polymerization of δ-valerolactone, the conversion rate is increased from 73% (continuous flow reactor) to 94% (macro-micro reactor). BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become more clear.

[0037] Figure 1 Schematic diagram of the overall device of macro-micro reactor, (a): homopolymerization, (b): copolymerization (Example 16).

[0038] Figure 2 Schematic diagram of the macro-microreactor with internal components containing immobilized enzymes.

[0039] Figure 3 For Example 3 polycaprolactone 1 H NMR spectra.

[0040] Figure 4 For Example 7 polyvalerolactone 1 H NMR spectra.

[0041] Figure 5 For Example 13 polytrimethylene carbonate 1 H NMR spectra.

[0042] Figure 6 Example 14 polyω-pentadecalactone 1 H NMR spectra.

[0043] Figure 7 For Example 16 poly(cyclohexylene tridecanedioate) 1 H NMR spectra.

[0044] Figure 8 Example 17 Poly (Z) - oxocycloheptadeca-8-ene-2-one 1 H NMR spectra. DETAILED DESCRIPTION

[0045] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0046] The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0047] In the present invention, PCL is polycaprolactone and PVL is polyvalerolactone.

[0048] The nuclear magnetic proton spectra in the following examples are as follows Figure 3-8 shown.

[0049] In the following examples of the present invention, the structure of the product was determined using a 400 MHz Bruker nuclear magnetic resonance instrument:

[0050] Take 5 mg of polyester sample and put it into NMR tube, add deuterated chloroform, shake until it is completely dissolved and then measure the sample.

[0051] In the following embodiments of the present invention, the number average molecular weight and molecular weight distribution of the product are measured by the following method:

[0052] A Wyatt WISH-01 gel permeation chromatograph was used, equipped with a flow pump (SSI Series 1500), a high-resolution gel chromatography column (Waters Styragel HR, 2.5 μm, 300×7.8 mm), and a static laser scattering instrument (Wyatt DAWNHELEOS II).

[0053] Test conditions: the mobile phase was tetrahydrofuran, the flow rate was 0.7 mL / min, the molecular weight and molecular weight distribution were tested by absolute method, dn / dc=0.1850.

[0054] Sample measurement: Take 8 mg of pure sample in a centrifuge tube, add 1.5 mL of tetrahydrofuran solution to dilute, and then filter with a disposable filter head (containing a 0.33 μm organic filter membrane) and take 0.4 mL of solution for sampling.

[0055] The macro-microreactor device used in the following examples is as follows: Figure 1 As shown, any of the following:

[0056] (a): It includes a feed pump 1 (Baoding Refu Fluid Technology Co., Ltd., TY01-01), a 50mL syringe 2, a digital pressure sensor 3 (Hangzhou Zhiwei Sensing Technology Co., Ltd., MIK-Y290), a macro-micro reactor 4, a heating device 5, and a reaction liquid receiving beaker 6. A polytetrafluoroethylene pipe with an outer diameter of 1.6 mm and an inner diameter of 1.0 mm (retaining volume 0.5 mL) is used to connect the syringe, the digital pressure sensor, and the macro-micro reactor in sequence, and a polytetrafluoroethylene pipe (retaining volume 0.3 mL) is used to connect the macro-micro reactor and the receiving beaker in sequence.

[0057] (b): including feed pumps ①② (Baoding Leifu Fluid Technology Co., Ltd., TY01-01), 50mL syringes ③④, digital pressure sensors ⑤⑥ (Hangzhou Zhiwei Sensing Technology Co., Ltd., MIK-Y290), macro-micro reactors ⑦⑧, heating devices ⑨⑩, and T-type mixers Reaction liquid receiving beaker Use polytetrafluoroethylene tubing (retained volume 0.5 mL) to connect syringe ③, digital pressure sensor ⑤, and macro-micro reactor ⑦ in sequence, and use polytetrafluoroethylene tubing (retained volume 0.6 mL) to connect macro-micro reactor ⑦ and syringe ④ in parallel to the T-type mixer (retention volume 0.2mL), and connected to the T-type mixer in sequence using a polytetrafluoroethylene tube (retention volume 0.5mL) The macro-microreactor⑧ was connected to the receiving beaker using polytetrafluoroethylene tubing (retention volume 0.3 mL).

[0058] like Figure 2 As shown, the macro-microreactor is composed of a polytetrafluoroethylene pipe and pure copper internal components. The pipe of the macro-microreactor is loaded with immobilized enzymes, and a small amount of cotton is used to block the pipe openings at both ends.

[0059] The preferred enzymes used in the following examples are Novozyme 435, with a particle size of 0.3-0.9 mm and an enzyme activity of 10,000 PLU / g, purchased from Nanjing Jiakai Technology Development Co., Ltd.; porcine pancreatic lipase, with an enzyme activity of 30,000 u / g, purchased from Nanjing Juyou Scientific Instrument Co., Ltd.; Candida rugosa lipase, with an enzyme activity of 700 u / mg, purchased from Nanjing Juyou Scientific Instrument Co., Ltd.; Amano lipase, purchased from Shanghai Titan Technology Co., Ltd.; Burkholderia cepacia lipase, with an enzyme activity of 23,000 u / mg, purchased from Shanghai McLean Biochemical Technology Co., Ltd.; Pseudomonas fluorescens lipase, with an enzyme activity of 20,000 u / g, purchased from Nanjing Wanqing Chemical Instrument Co., Ltd. Before each use, the macro-microreactor is repeatedly rinsed with toluene (selected according to the solvent used to prepare the reaction solution, preferably toluene) to purify the pipeline.

[0060] Parameters of macro and micro reactors (unit: mm):

[0061] (1) For the helical internals reactor, it is named according to the inner diameter (D) of the pipe, the diameter of the copper wire (d) and the helical pitch (l3). For example, the reactor HSI (2-0.5-2) represents an internals reactor made of a pipe with an inner diameter of 2 mm and a helical copper wire with a diameter of 0.5 mm and a pitch of 2 mm;

[0062] (2) For linear internals reactors, they are named according to the inner diameter (D) of the pipe and the diameter (d) of the copper wire. For example, the reactor SLSI (3-0.5) represents an internals reactor made of a pipe with an inner diameter of 3 mm and a straight copper wire with a diameter of 0.5 mm;

[0063] (3) For the serpentine internal component reactor, it is named according to the direction of the copper wire, the inner diameter of the pipe (D), the copper wire diameter (d) and the unit length of the serpentine wire (l1). For example, the reactor SSID-1 (3-1.5-10) represents an internal component reactor made by adding a serpentine copper wire with a diameter of 1.5 mm and a unit length of 10 mm to a pipe with an inner diameter of 3 mm, with the center plane of the serpentine copper wire parallel to the center plane of the pipe inlet and outlet; the reactor SSID-2 (4-1.5-3) represents an internal component reactor made by adding a serpentine copper wire with a diameter of 1.5 mm and a unit length of 3 mm to a pipe with an inner diameter of 4 mm;

[0064] (4) For O-shaped internal component reactors, they are named according to the inner diameter of the pipe (D), the diameter of the O-ring (d3) and the distance between adjacent O-rings (l2). For example, the reactor OSI (4-0.5-3) represents an internal component reactor made of an O-ring copper wire with a diameter of 0.5 mm added to a pipe with an inner diameter of 4 mm and a distance between adjacent O-rings of 3 mm.

[0065]

[0066] Example 1

[0067] 1.2 g of Lipase from Candida rugosa (CRL) was uniformly filled into the macro-microreactor HSI (2-0.5-2) (retention volume was 2.0 mL). The 100 mL spherical reaction bottle was baked at high temperature and the gas was replaced with argon using Schlenk technology, and repeated three times. Purified ε-caprolactone (22.828 g (21.35 mL), 200 mmol, molecular weight: 114.14) and initiator benzyl alcohol (0.2163 g (0.21 mL), 2 mmol, molecular weight: 108.138) were added to the reaction bottle under argon environment. The dried toluene (28.44 mL) was prepared into 50.0 mL solution (monomer concentration: [M]0 = 4 mol / L) and oscillated to mix. The reaction pipe was heated to 60°C in a water bath. 25 mL of toluene was used to flush the pipe, and the flow rate of the injection pump was set to 1 mL / min to remove oxygen and water from the pipe. A 50 mL syringe was used to extract the reaction solution and pumped into the macro-microreactor. The flow rate of the injection pump was set to 0.2 mL / min, i.e., the residence time of the ring-opening polymerization reaction was 10 min. The reaction was started, and after 20 min of reaction stabilization, the reaction solution was collected and used 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polycaprolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 76%, and the output per minute was 0.031 g. The number average molecular weight of the polycaprolactone product was determined by 1 The molecular weight was calculated by H NMR and was 8800 g / mol. The molecular weight distribution index was determined by GPC and was 1.30.

[0068] Example 2

[0069] 8.4 g of Amano Lipase from Pseudomonas fluorescens was uniformly filled into the macro-microreactor HSI (3-1-3) (retention volume was 14.0 mL). The 100 mL spherical reaction bottle was baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Purified ε-caprolactone (11.414 g (10.67 mL), 100 mmol, molecular weight: 114.14) and initiator 6-mercapto-1-hexanol (0.1342 g (0.14 mL), 1 mmol, molecular weight: 134.240) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M]0 = 2 mol / L) was prepared using toluene (39.19 mL) after redispersion and drying, and oscillated to mix. The reaction pipe was heated to 60 ° C in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 2mL / min, that is, the residence time of the ring-opening polymerization reaction is 7min. Start the reaction, wait for 14min for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polycaprolactone was 1 HNMR identification. The monomer conversion rate during the polymerization process reached 83%, and the output per minute was 0.341 g. The number average molecular weight of the polycaprolactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.27.

[0070] Example 3

[0071] Synthesis method of N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide: Add 5-norbornene-exo-2,3-dicarboxylic anhydride (10.0 g, 61.0 mmol, molecular weight: 164.16), 6-amino-1-hexanol (7.5 g, 64.0 mmol, molecular weight: 117.19) and toluene (120 mL) into a 250 mL round-bottom flask and stir to mix. Build a Dean-Stark apparatus with a condenser. Heat the reaction to 130 ° C until the solution begins to reflux and react for 12 hours. Take a trace amount of the reaction solution to test the nuclear magnetic resonance hydrogen spectrum, and stop heating the reaction after the reaction conversion is complete. After waiting for the reaction solution to return to room temperature, use a rotary evaporator to remove the solvent and dissolve the remaining product in dichloromethane (250 mL). Use 0.1mol / L hydrochloric acid aqueous solution (50mL) to extract three times, take the organic phase, and then use saturated common salt water solution (50mL) to extract once. The organic phase obtained by extraction is dried over anhydrous magnesium sulfate to remove residual moisture. Use rotary evaporator to remove solvent to obtain a crude reaction product, and the crude product is dried in a vacuum drying oven for 12h to obtain a light yellow N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide. Add 4A molecular sieves under argon environment and store in a glove box under argon environment.

[0072] 9.0 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor HSI (4-1-3) (retention volume was 15.0 mL). The 100 mL spherical reaction bottle was baked at high temperature and the gas was replaced with argon using Schlenk technology, and repeated three times. Purified ε-caprolactone (17.121 g (16.01 mL), 150 mmol, molecular weight: 114.14) and initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.1315 g (0.12 mL), 0.5 mmol, molecular weight: 263) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M]0 = 3 mol / L) was prepared using toluene (33.87 mL) after redispersion and drying, and oscillated and mixed. The reaction pipe was heated to 60° C. in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 1mL / min, that is, the residence time of the ring-opening polymerization reaction is 15min. Start the reaction, wait for 30min for the reaction to stabilize, collect the reaction liquid, and use 1The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polycaprolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 77%, and the output per minute was 0.237 g. The number average molecular weight of the polycaprolactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.31.

[0073] Example 4

[0074] 9.6 g of lipase PS from Burkholderia cepacia (LPS) was uniformly filled into the macro-microreactor HSI (6-1.8-4) (retention volume was 16.0 mL). The 100 mL spherical reaction bottle was baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Purified ε-caprolactone (11.414 g (10.67 mL), 100 mmol, molecular weight: 114.14) and initiator 5-hexen-1-ol (0.2003 g (0.24 mL), 2 mmol, molecular weight: 100.16) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M]0 = 2 mol / L) was prepared using toluene (39.09 mL) after redispermment and drying, and oscillated to mix. The reaction pipe was heated to 60 ° C in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 8mL / min, that is, the residence time of the ring-opening polymerization reaction is 2min. Start the reaction, wait for 4min for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polycaprolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 92%, and the output per minute was 1.512 g. The number average molecular weight of the polycaprolactone product was determined by 1 The molecular weight was calculated by H NMR and was 5400 g / mol. The molecular weight distribution index was determined by GPC and was 1.22.

[0075] Example 5

[0076] 9.6 g of Pseudomonas fluorescens lipase (PF) was uniformly filled into the macro-microreactor HSI (8-3-6) (retention volume was 16.0 mL). The 100 mL spherical reaction bottle was baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Purified ε-caprolactone (0.5707 g (0.53 mL), 5 mmol, molecular weight: 114.14) and initiator 3-thiophene methanol (0.0571 g (0.05 mL), 0.5 mmol, molecular weight: 114.17) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M]0 = 0.1 mol / L) was prepared using toluene (49.42 mL) after redispersion and drying, and oscillated to mix. The reaction pipe was heated to 55 ° C in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 8mL / min, that is, the residence time of the ring-opening polymerization reaction is 2min. Start the reaction, wait for 4min for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polycaprolactone was 1 HNMR identification. The monomer conversion rate during the polymerization process reached 86%, and the output per minute was 0.071 g. The number average molecular weight of the polycaprolactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.27.

[0077] Example 6

[0078] 12.0 g of porcine pancreatic lipase was uniformly filled into the macro-microreactor HSI (10-3-10) (retention volume was 20.0 mL). The 100 mL spherical reaction bottle was baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Purified ε-caprolactone (11.414 g (10.67 mL), 100 mmol, molecular weight: 114.14) and initiator pyridine-3-methanol (0.5457 g (0.49 mL), 5 mmol, molecular weight: 109.13) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M]0 = 2 mol / L) was prepared using n-hexane (38.84 mL) after redispermment and drying, and oscillated and mixed. The reaction pipeline was heated to 70 ° C in a water bath. The pipeline was flushed with 25 mL of n-hexane, and the flow rate of the injection pump was set to 1 mL / min to remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction solution and pump it into the macro-microreactor. Set the flow rate of the syringe pump to 10mL / min, that is, the residence time of the ring-opening polymerization reaction is 2min. Start the reaction. After the reaction is stable for 4min, collect the reaction solution and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polycaprolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 89%, and the output per minute was 1.829 g. The number average molecular weight of the polycaprolactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.29.

[0079] Example 7

[0080] 9.0 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor HSI (4-1-3) (retention volume was 15.0 mL). The 100 mL spherical reaction bottle was baked at high temperature using Schlenk technology and the gas was replaced with argon, which was repeated three times. Purified δ-valerolactone monomer (10.0 g (9.05 mL), 100 mmol, molecular weight: 100.12) and initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.2631 g (0.23 mL), 1 mmol, molecular weight: 263) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M] 0 = 2 mol / L) was prepared using toluene (40.72 mL) after redispersion and drying, and oscillated to mix. The reaction pipe was heated to 60° C. in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 5mL / min, that is, the residence time of the ring-opening polymerization reaction is 3min. Start the reaction, wait for 6 minutes for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polyvalerolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 94%, the output per minute was 0.957 g, and the number average molecular weight of the polyvalerolactone product was determined by 1 The molecular weight was calculated by H NMR and was 9800 g / mol. The molecular weight distribution index was determined by GPC and was 1.10.

[0081] Example 8

[0082] 9.0 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor HSI (4-1-3) (retention volume was 15.0 mL). The 100 mL spherical reaction bottle was baked at high temperature using Schlenk technology and the gas was replaced with argon, which was repeated three times. Purified δ-valerolactone monomer (10.0 g (9.05 mL), 100 mmol, molecular weight: 100.12) and initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.2631 g (0.23 mL), 1 mmol, molecular weight: 263) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M] 0 = 2 mol / L) was prepared using toluene (40.72 mL) after redispersion and drying, and oscillated and mixed. The reaction pipeline was kept at 0°C in an ice bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 5mL / min, that is, the residence time of the ring-opening polymerization reaction is 3min. Start the reaction, wait for 6 minutes for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polyvalerolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 7%, the output per minute was 0.063 g, and the number average molecular weight of the polyvalerolactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.65.

[0083] Example 9

[0084] 9.0 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor HSI (4-1-3) (retention volume was 15.0 mL). The 100 mL spherical reaction bottle was baked at high temperature using Schlenk technology and the gas was replaced with argon, which was repeated three times. Purified δ-valerolactone monomer (10.0 g (9.05 mL), 100 mmol, molecular weight: 100.12) and initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.2631 g (0.23 mL), 1 mmol, molecular weight: 263) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M] 0 = 2 mol / L) was prepared using toluene (40.72 mL) after redispermment and drying, and oscillated to mix. The reaction pipe was heated to 25° C. in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 5mL / min, that is, the residence time of the ring-opening polymerization reaction is 3min. Start the reaction, wait for 6 minutes for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polyvalerolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 69%, the output per minute was 0.621 g, and the number average molecular weight of the polyvalerolactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.35.

[0085] Example 10

[0086] 7.2 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into a macro-microreactor SLSI (3-0.5) (retention volume was 12.0 mL). The 100 mL spherical reaction bottle was baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Purified δ-valerolactone monomer (20.0 g (18.10 mL), 200 mmol, molecular weight: 100.12) and initiator 6-mercapto-1-hexanol (0.6712 g (0.68 mL), 5 mmol, molecular weight: 134.240) were added to the reaction bottle under argon environment, and 50.0 mL solution (monomer concentration: [M] 0 = 4 mol / L) was prepared using toluene (31.22 mL) after redispersion and drying, and oscillated and mixed. The reaction pipeline was heated to 60° C. in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 4mL / min, that is, the residence time of the ring-opening polymerization reaction is 3min. Start the reaction, wait for 6min for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polyvalerolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 92%, the output per minute was 1.325 g, and the number average molecular weight of the polyvalerolactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.15.

[0087] Embodiment 11

[0088] 1.5 g of immobilized enzyme Novozyme435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor SSID-1 (3-1.5-10) (retention volume was 2.4 mL). The 100 mL spherical reaction bottle was baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Purified δ-valerolactone monomer (10.0 g (9.05 mL), 100 mmol, molecular weight: 100.12) and initiator benzyl alcohol (0.1081 g (0.10 mL), 1 mmol, molecular weight: 108.138) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M] 0 = 2 mol / L) was prepared using toluene (40.85 mL) after redispermment and drying, and oscillated and mixed. The reaction pipe was heated to 60 ° C in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 0.2mL / min, that is, the residence time of the ring-opening polymerization reaction is 12min. Start the reaction, wait for 24min for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polyvalerolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 86%, and the output per minute was 0.031 g. The number average molecular weight of the polyvalerolactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.18.

[0089] Example 12

[0090] 1.2 g of immobilized enzyme Novozyme435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor SSID-2 (4-1.5-3) (retention volume was 2.0 mL). The 100 mL spherical reaction bottle was baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Trimethylene carbonate monomer (10.2 g, 100 mmol, molecular weight: 102.09) and initiator benzyl alcohol (0.2163 g (0.21 mL), 2 mmol, molecular weight: 108.138) were added to the reaction bottle under argon environment, and 50.0 mL solution (monomer concentration: [M] 0 = 2 mol / L) was prepared using toluene (41.63 mL) after redispermment and drying, and oscillated and mixed. The reaction pipeline was heated to 90 ° C in a water bath. 25 mL of toluene was used to flush the pipeline, and the flow rate of the injection pump was set to 1 mL / min to remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction solution and pump it into the macro-microreactor. Set the flow rate of the syringe pump to 0.2mL / min, that is, the residence time of the ring-opening polymerization reaction is 10min. Start the reaction. After 20min of stable reaction, collect the reaction solution and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polytrimethylene carbonate was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 93%, and the output per minute was 0.034 g. The number average molecular weight of the polytrimethylene carbonate product was determined by 1 The molecular weight was calculated by H NMR and was 4900 g / mol. The molecular weight distribution index was determined by GPC and was 1.16.

[0091] Embodiment 13

[0092] 9 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor HSI (4-1-3) (retention volume was 15.0 mL). The 100 mL spherical reaction bottle was baked at high temperature using Schlenk technology and the gas was replaced with argon, which was repeated three times. Trimethylene carbonate monomer (10.2 g, 100 mmol, molecular weight: 102.09) and initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (2.63 g (2.3 mL), 10 mmol, molecular weight: 263) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M]0 = 2 mol / L) was prepared using toluene (39.54 mL) after redispersion and drying, and oscillated to mix. The reaction pipe was heated to 60° C. in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 3mL / min, that is, the residence time of the ring-opening polymerization reaction is 5min. Start the reaction, wait for 10 minutes for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polytrimethylene carbonate was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 98%, and the output per minute was 0.540 g. The number average molecular weight of the polytrimethylene carbonate product was determined by 1 The molecular weight was calculated by H NMR and was 1300 g / mol. The molecular weight distribution index was determined by GPC and was 1.14.

[0093] Embodiment 14

[0094] 2.4 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor HSI (4-1-3) (retention volume was 4.0 mL). The 100 mL spherical reaction bottle was baked at high temperature using Schlenk technology and the gas was replaced with argon, which was repeated three times. In an argon environment, ω-pentadecalactone monomer (4.81 g, 20 mmol, molecular weight: 240.38) and initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.263 g (0.23 mL), 1 mmol, molecular weight: 263) were added to the reaction bottle, and toluene (44.53 mL) after redispermment and drying was used to prepare 50.0 mL of solution (monomer concentration: [M] 0 = 0.4 mol / L), and oscillated and mixed. The reaction pipeline was heated to 60° C. in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 2mL / min, that is, the residence time of the ring-opening polymerization reaction is 2min. Start the reaction, wait for 4min for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polypentadecalactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 93%, and the output per minute was 0.161 g. The number average molecular weight of the polypentadecalactone product was determined by 1 The molecular weight was calculated by H NMR and was 4800 g / mol. The molecular weight distribution index was determined by GPC and was 1.15.

[0095] Embodiment 15

[0096] 2.4 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor OSI (4-0.5-3) (retention volume was 4.0 mL). The 100 mL spherical reaction bottle was baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. In an argon environment, ω-pentadecalactone monomer (4.81 g, 20 mmol, molecular weight: 240.38) and initiator 6-mercapto-1-hexanol (0.1342 g (0.14 mL), 1 mmol, molecular weight: 134.240) were added to the reaction bottle, and 50.0 mL of solution (monomer concentration: [M] 0 = 0.4 mol / L) was prepared using toluene (44.62 mL) after redispermment and drying, and oscillated and mixed. The reaction pipeline was heated to 90 ° C in a water bath. 25 mL of toluene was used to flush the pipeline, and the flow rate of the injection pump was set to 1 mL / min to remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction solution and pump it into the macro-microreactor. Set the flow rate of the syringe pump to 0.8mL / min, that is, the residence time of the ring-opening polymerization reaction is 5min. Start the reaction. After the reaction is stable for 10min, collect the reaction solution and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polypentadecalactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 91%, and the output per minute was 0.063 g. The number average molecular weight of the polypentadecalactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.23.

[0097] Example 16

[0098] 3.0 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor HSI (6-1.8-4) (retention volume was 5.0 mL). The 100 mL spherical reaction bottle was baked at high temperature using Schlenk technology and the gas was replaced with argon, which was repeated three times. Tridecane dioic acid cyclohexyl ester monomer (5.4073 g, 20 mmol, molecular weight: 270.365) and initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.263 g (0.23 mL), 1 mmol, molecular weight: 263) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M] 0 = 0.4 mol / L) was prepared using toluene (44.58 mL) after redispermment and drying, and oscillated and mixed. The reaction pipeline was heated to 60° C. in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 1mL / min, that is, the residence time of the ring-opening polymerization reaction is 5min. Start the reaction, wait for 10 minutes for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained poly(cyclohexylene tridecanedioate) was prepared by 1 H NMR identification. The monomer conversion rate during the polymerization process reached 92%, and the output per minute was 0.090 g. The number average molecular weight of the poly(cyclohexylene tridecanedioate) product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.22.

[0099] Embodiment 17

[0100] 3.6 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor HSI (6-1.8-4) (retention volume was 6.0 mL). The 100 mL spherical reaction bottle was baked at high temperature using Schlenk technology and the gas was replaced with argon, which was repeated three times. (Z)-oxocycloheptadec-8-ene-2-one monomer (5.0478 g, 20 mmol, molecular weight: 252.39) and initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.263 g (0.23 mL), 1 mmol, molecular weight: 263) were added to the reaction bottle under argon environment, and 50.0 mL of solution (monomer concentration: [M]0 = 0.4 mol / L) was prepared using toluene (44.49 mL) after redispersion and drying, and oscillated and mixed. The reaction pipeline was heated to 60° C. in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the macro-microreactor, set the flow rate of the injection pump to 2mL / min, that is, the residence time of the ring-opening polymerization reaction is 3min. Start the reaction, wait for 6min for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained poly (Z)-oxycycloheptadecan-8-ene-2-one was prepared by 1 H NMR identification. The monomer conversion rate during the polymerization process reached 93%, and the output per minute was 0.169 g. The number average molecular weight of the poly (Z) - oxocycloheptadecan-8-ene-2-one product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.18.

[0101] Embodiment 18

[0102] 1.8g and 9.6g of immobilized enzyme Novozyme435 with a particle size of 0.3-0.9mm were uniformly filled into the macro-microreactor HSI (4-1-3) ① and ② respectively (retention volumes were 3.0mL and 16.0mL respectively). Two 25mL spherical reaction bottles A and B were baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Purified ε-caprolactone monomer (8.2g (7.67mL), 72mmol, molecular weight: 114.14) and initiator 6-mercapto-1-hexanol (0.32g (0.33mL), 2.4mmol, molecular weight: 134.24) were added to the reaction bottle A under argon environment, and 18.0mL solution A (monomer concentration: [CL]0 = 4mol / L) was prepared using toluene (10.0mL) after redispersion and drying. Add purified δ-valerolactone monomer (7.2 g (6.5 mL), 72 mmol, molecular weight: 100.12) into reaction flask B, and use toluene (11.5 mL) that has been redispersed and dried to prepare 18.0 mL of solution B (monomer concentration: [VL]0 = 2 mol / L). Transfer solutions A and B to two 50 mL syringes. Heat the reaction pipeline to 60°C in a water bath. Rinse the pipeline with 25 mL of toluene, set the flow rate of the injection pump to 1 mL / min, and remove oxygen and water in the pipeline. Pump solution A into the macro-microreactor HSI (4-1-3) ① at a flow rate of 1 mL / min, and the residence time in the reactor is 3 min. The resulting effluent and solution B are pumped into the macro-microreactor HSI (4-1-3) ② at a flow rate of 1 mL / min, and the residence time in the reactor is 8 min. Collect the reaction solution and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained block copolymer PCL 30- b-PVL 30 pass 1 H NMR identification. During the polymerization process, the conversion rate of ε-caprolactone monomer reached 96%, the conversion rate of δ-valerolactone monomer reached 97%, the block copolymer output per minute was 0.74g, and the number average molecular weight was 1 The molecular weight distribution index was determined by GPC and was 1.17.

[0103] Example 19 A method for preparing degradable polyester based on macro-microreactor ring-opening polyester

[0104] 15.0 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm was uniformly filled into the macro-microreactor HSI (3-1-3) (retention volume was 25.0 mL). The 100 mL spherical reaction bottle was baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Purified δ-valerolactone monomer (10.0 g (9.05 mL), 100 mmol, molecular weight: 100.12 g), initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.2631 g (0.23 mL), 1 mmol, molecular weight: 263) and dry toluene (40.72 mL) were added to the reaction bottle under argon environment to prepare 50.0 mL solution ([M] 0 = 2 mol / L), and oscillated to mix. 25mL toluene was used to flush the pipeline to remove oxygen and water in the pipeline. A 50mL gas-tight syringe was used to extract the reaction solution and pump it into the immobilized enzyme macro-microreactor. The flow rate of the syringe pump was set to 5mL / min, the reaction residence time was 5min, the reaction pipeline device was heated to 60°C in a water bath, the reaction solution was collected, and the reaction conversion rate was calculated to be 95% using 1H NMR. The product was collected by centrifugation with cold methanol precipitation, and the solvent dissolution precipitation centrifugation process was repeated three times to fully wash the product, which was placed in a vacuum drying oven and dried at room temperature for 48h to obtain a polyvalerolactone product with a number average molecular weight of 11000g / mol and a molecular weight distribution index of 1.10.

[0105] Comparative Example 1

[0106] In a kettle reactor, a 100 mL spherical reaction bottle was baked at high temperature and the gas was replaced with argon using Schlenk technology, and repeated three times. Purified δ-valerolactone monomer (10.0 g (9.05 mL), 100 mmol, molecular weight: 100.12), initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.2631 g (0.23 mL), 1 mmol, molecular weight: 263) and 1.8 g immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm were added to the reaction bottle under argon environment. 50.0 mL of solution (monomer concentration: [M] 0 = 2 mol / L) was prepared using toluene (40.72 mL) that had been redispersed and dried, and the solution was shaken and mixed. The reaction bottle was placed in a 60°C water bath and stirred for 8 hours. After the reaction was completed, the reaction solution was collected and used 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polycaprolactone was 1H NMR identification. The monomer conversion rate during the polymerization process reached 81%, and the output per minute was 0.017 g. The number average molecular weight of the polycaprolactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.56.

[0107] Comparative Example 2

[0108] The continuous flow reactor has an inner diameter of 4 mm. 9.0 g of immobilized enzyme Novozyme 435 with a particle size of 0.3-0.9 mm is uniformly filled into the pipeline (retention volume 15.0 mL). The 100 mL spherical reaction bottle is baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Purified δ-valerolactone monomer (10.0 g (9.05 mL), 100 mmol, molecular weight: 100.12) and initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.2631 g (0.23 mL), 1 mmol, molecular weight: 263) are added to the reaction bottle under argon environment. 50.0 mL solution (monomer concentration: [M] 0 = 2 mol / L) is prepared using toluene (40.72 mL) after redispersion and drying, and oscillated and mixed. The reaction pipeline is heated to 60° C. in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the continuous flow reactor, set the flow rate of the injection pump to 5mL / min, that is, the residence time of the ring-opening polymerization reaction is 3min. Start the reaction, wait for 6 minutes for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polycaprolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 73%, and the output per minute was 0.657 g. The number average molecular weight of the polycaprolactone product was determined by 1 The molecular weight distribution index was determined by GPC and was 1.22.

[0109] Comparative Example 3

[0110] Microreactor, the inner diameter of the pipeline is 1mm, and 0.27g of immobilized enzyme Novozyme435 with a particle size of 0.3-0.9mm is evenly filled into the pipeline (retention volume 0.45mL). The 100mL spherical reaction bottle is baked at high temperature and replaced with argon using Schlenk technology, and repeated three times. Purified δ-valerolactone monomer (10.0g (9.05mL), 100mmol, molecular weight: 100.12) and initiator N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (0.2631g (0.23mL), 1mmol, molecular weight: 263) are added to the reaction bottle under argon environment, and 50.0mL solution (monomer concentration: [M]0=2mol / L) is prepared using toluene (40.72mL) after redispermment and drying, and oscillated and mixed. The reaction pipeline is heated to 60°C in a water bath. Use 25mL of toluene to flush the pipeline, set the flow rate of the injection pump to 1mL / min, and remove oxygen and water in the pipeline. Use a 50mL syringe to extract the reaction liquid and pump it into the continuous flow reactor, set the flow rate of the injection pump to 0.15mL / min, that is, the residence time of the ring-opening polymerization reaction is 3min. Start the reaction, wait for 6 minutes for the reaction to stabilize, collect the reaction liquid, and use 1 The monomer conversion rate was calculated by H NMR. Cold methanol was added to the remaining reaction solution and allowed to settle. The precipitate was obtained by centrifugation. The precipitate was dissolved in dichloromethane and separated again according to the above steps. The separation and purification steps were repeated three times. The obtained product was placed in a vacuum drying oven at 35°C and dried for 48 hours. The obtained polyvalerolactone was 1 H NMR identification. The monomer conversion rate during the polymerization process reached 96%, and the output per minute was 0.026 g. The number average molecular weight of the polyvalerolactone product was determined by 1 The molecular weight was calculated by H NMR and was 9900 g / mol. The molecular weight distribution index was determined by GPC and was 1.12.

[0111] The present invention is based on the macro-microreactor platform enzyme-catalyzed ring-opening polymerization to prepare degradable polyester, and the reaction is efficient and controllable. By introducing spiral internal components, the typical microreactor and continuous flow reactor are optimized, the flux is increased while retaining the microscale effect, the mass transfer and heat transfer efficiency is greatly improved, the pressure drop is reduced, and the degradable polyester with controllable molecular weight and narrow molecular weight distribution can be efficiently prepared.

[0112] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. An application of a macro-microreactor in the preparation of degradable polyester; preferably, the degradable polyester is prepared using a cyclic monomer as a raw material; preferably, in a macro-microreactor, a cyclic monomer, an initiator, a catalyst, and a solvent are reacted to obtain the degradable polyester.

2. A method for preparing degradable polyester based on macro-micro reactor ring opening, characterized in that: In a macro-microreactor, a cyclic monomer, an initiator, a catalyst and a solvent are reacted to obtain a degradable polyester.

3. The use according to claim 1 or the method according to claim 2, characterized in that: The cyclic monomers are ε-caprolactone, δ-valerolactone, trimethylene carbonate, pentadecacyclic lactone, cyclohexanediolate, and (Z)-oxocycloheptadeca-8-ene-2-one.

4. The use according to claim 1 or the method according to claim 2, characterized in that: The initiator is an alcohol, and the alcohol includes benzyl alcohol, phenylpropanol, N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide, 5-hexene-1-ol, 3-butyn-1-ol, and 6-bromo-1-hexanol.

5. The use according to claim 1 or the method according to claim 2, characterized in that: The cyclic monomer is any combination of ε-caprolactone, δ-valerolactone, trimethylene carbonate, pentadecacyclic lactone, cyclohexanediol and (Z)-oxocycloheptadecan-8-ene-2-one; preferably, the initiator includes 6-mercapto-1-hexanol, 3-thiophene methanol, pyridine-3-methanol; preferably, the molar mass ratio of the monomer to the catalyst is 0.5-200:1; preferably, the flow rate of the reaction is 0.2-10 mL / min; preferably, the solvent includes n-hexane and dichloromethane.

6. The use according to claim 1 or the method according to claim 2, characterized in that: The solvent of the reaction is tetrahydrofuran, toluene, and dichloromethane; the catalyst is an enzyme filled in a macro-microreactor, and the enzyme includes an Antarctic Candida enzyme, porcine pancreatic lipase, Candida plicata enzyme, Amano lipase, Burkholderia cepacia enzyme, Pseudomonas fluorescens lipase, and Candida plicata, preferably immobilized Antarctic Candida enzyme Novozyme435.

7. The use according to claim 1 or the method according to claim 2, characterized in that: The molar ratio of the monomer to the initiator is 10-300:

1.

8. The use according to claim 1 or the method according to claim 2, characterized in that: The monomer concentration is 0.1-4 mol / L, preferably 2 mol / L.

9. The use according to claim 1 or the method according to claim 2, characterized in that: The macro-microreactor comprises an outer shell and an internal component; preferably, the retention volume of the macro-microreactor is 1-30 mL; preferably, the inner diameter of the macro-microreactor is 1-10 mm, and the diameter of the internal component is 0.5-3 mm; preferably, the internal component is a linear internal component; preferably, the internal component is a spiral internal component, a serpentine internal structure, or an O-shaped internal component, which has a pitch, and the pitch of the internal component is 1-10 mm.

10. The use according to claim 1 or the method according to claim 2, characterized in that: The inner diameter of the macro-microreactor is 1-10 mm, the diameter of the spiral inner member is 0.5-3 mm, and the pitch is 1-10 mm; preferably, the reaction temperature is 0-90°C, preferably 60°C.

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