Method for preparing degradable polyester based on macro-micro reactor organic ring opening polymerization

Abstract

The invention discloses a method for preparing degradable polyester based on organic ring opening polymerization of a macro-micro reactor. A cyclic monomer, an initiator, a catalyst and a solvent are placed in the macro-micro reactor to react to obtain the degradable polyester. The method is suitable for cyclic monomers and hydroxyl initiators, the applicable substrate range is wide, compared with a traditional synthesis method, the macro-micro reactor which contains internal components and has the characteristic scale reaching the centimeter level can remarkably shorten the organic catalysis transesterification promoting reaction time, the conversion rate is effectively increased, and meanwhile high-flux synthesis can be achieved. The invention provides a technical scheme for organic catalytic synthesis of new materials, and has a great prospect in the aspect of organic catalytic synthesis of new materials.

Description

Technical Field

[0001] The invention relates to the technical field of organic catalytic synthesis of cyclic monomers, and in particular to a method for preparing degradable polyester based on organic ring-opening polymerization of macro- and micro-reactors. Background Art

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

[0003] Aliphatic polyester materials are now extremely important biodegradable materials with excellent biodegradability, biocompatibility and mechanical strength. They are used in conduction systems, tissue engineering and daily necessities. The most studied ring-opening polymerizations today are metal catalysts, organic catalysts and enzymes. However, general metal catalysts are sensitive to water and air, which makes the reaction conditions very harsh, and the use of metal catalysts will cause metal residues in the polymer, thus limiting its performance and application. Organic catalysts can be used under milder reaction conditions to avoid metal residues in the polymer. For example, most organic catalysts represented by DBU have low catalytic activity and are only applicable to some polyester systems, and the catalyst dosage is often large. TBD is a highly active ring-opening polymerization catalyst. The polymerization reaction catalyzed by it is not only very fast, but also the experimental results show that the polymerization process is controllable / active. However, the PDI will become relatively wide due to ester exchange during the reaction.

[0004] Compared with the kettle reactor, the microreactor has the advantages of enhanced mixing, heat transfer and mass transfer in the flow and good time and space controllability, but still has the disadvantages of small flux, large pressure drop and easy clogging. The macro-microreactor inherits the advantages of the microreactor and overcomes this disadvantage. Therefore, the present invention is based on the macro-microreactor to carry out organic catalytic transesterification reaction, shorten the transesterification reaction time, and improve the conversion rate. The characteristic scale of the macro-microreactor reaches the centimeter level, which can achieve high-throughput synthesis. Summary of the invention

[0005] Purpose of the invention: The technical problem to be solved by the present invention is to provide a method for preparing degradable polyester based on organic ring-opening polymerization in macro- and micro-reactors in view of the deficiencies in the prior art.

[0006] In order to solve the above technical problems, the present invention discloses the following technical solutions:

[0007] In a first aspect, the present invention discloses an application of a macro-micro reactor in the preparation of degradable polyester, characterized in that a cyclic monomer, an initiator, a catalyst, and a solvent are placed in a macro-micro reactor to react to obtain the degradable polyester.

[0008] In a second aspect, the present invention discloses a method for preparing degradable polyester based on macro-microreactor ring-opening polyester, wherein cyclic monomers, initiators, catalysts, and solvents are placed in macro-microreactors for reaction to obtain degradable polyester.

[0009] In the first and second aspects above,

[0010] Wherein, the cyclic monomer is ε-caprolactone (a), δ-valerolactone (b), trimethylene carbonate (c), lactide (d), pentadecacyclic lactone (e), tridecanedioic acid cyclohexylene ester (f), (Z)-oxycycloheptadeca-8-ene-2-one (g), or any combination of the foregoing.

[0011]

[0012] Wherein, the initiator is an alcohol, including a benzyl alcohol, b phenylpropanol, c N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide, d 5-hexene-1-ol, e 3-butyn-1-ol, and f 6-bromo-1-hexanol.

[0013]

[0014] Among them, the catalyst is 1,5,7-triazidobicyclo(4.4.0)dec-5-ene (TBD), diphenyl phosphate (DPP), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), 4-dimethylaminopyridine (DMAP), etc.

[0015]

[0016] Wherein, the solvent of the reaction is tetrahydrofuran, toluene, dichloromethane and the like.

[0017] Wherein, the ratio of the monomer to the catalyst is 10-300:1, such as 100:1, 150:1, 200:1, 250:1.

[0018] Wherein, the monomer concentration is 0.1-4 mol / L, such as 1 mmol / L, 2 mol / L, 3 mmol / L.

[0019] Wherein, the flow rate of the reaction is 0.5-30 mL / min, such as 5 mL / min, 1 mL / min, 10 mL / min, 15 mL / min, 20 mL / min.

[0020] In some embodiments, the monomer and the first solvent are made into a first solution, and the initiator, the catalyst, and the second solvent are made into a second solution; the first solution and the second solution are pumped into the macro-micro reactor respectively for reaction. The first solvent and the second solvent may be the same or different; in the first solution, the concentration of the monomer is 0.1-10mmol / mL, such as 0.2mmol / mL, 0.5mmol / mL, 1mmol / mL, 1.5mmol / mL, 2mmol / mL, 3mmol / mL, 4mmol / mL, 5mmol / mL; in the second solution, the concentration of the initiator is 0.02-1mmol / mL, such as 0.04mmol / mL, 0.08mmol / mL, 0.1mmol / mL, 0.2mmol / mL, 0.6mmol / mL.

[0021] In some embodiments, a first monomer and a first solvent are made into a first solution, an initiator, a catalyst, and a second solvent are made into a second solution, and a second monomer and a third solvent are made into a third solution; the first solution and the second solution are respectively pumped into a first macro-microreactor for a first reaction, and the first reaction effluent and the third solution are respectively pumped into a second macro-microreactor for a second reaction; wherein the first solvent, the second solvent, and the third solvent may be the same or different; the first monomer and the second monomer are different monomers; in the first solution, the concentration of the first monomer is 0.1-10 mmol / mL, such as 0.2 mmol / mL, 0.5 mmol / mL, 1 mmol / mL, 1.5 mmol / mL, l / mL, 2mmol / mL, 3mmol / mL, 4mmol / mL, 5mmol / mL; in the second solution, the concentration of the initiator is 0.02-1mmol / mL, such as 0.04mmol / mL, 0.08mmol / mL, 0.1mmol / mL, 0.2mmol / mL, 0.6mmol / mL; in the third solution, the concentration of the second monomer is 0.1-10mmol / mL, such as 0.2mmol / mL, 0.5mmol / mL, 1mmol / mL, 1.5mmol / mL, 2mmol / mL, 3mmol / mL, 4mmol / mL, 5mmol / mL.

[0022] Wherein, the macro-microreactor includes a microchannel pipeline, and an internal component is arranged inside the microchannel pipeline. The retention volume of the macro-microreactor is 2 to 50 mL, such as 5 mL, 36 mL; the inner diameter of the microchannel pipeline is 1-10 mm; the diameter of the internal component is 0.5-3 mm; the internal component is a spiral internal component, a serpentine internal component, an O-shaped internal component, or a linear internal component; the spiral internal component, the serpentine internal structure and the O-shaped internal component have a pitch of 1-10 mm. In some embodiments, the internal component is a copper internal component.

[0023] Wherein, the inner diameter of the macro-microreactor is 1-10 mm, the diameter of the spiral inner component is 0.5-3 mm, and the pitch is 1-10 mm.

[0024] In some embodiments, the reaction system includes a mixer, which may be a Y-shaped inlet channel. The structural parameters of the Y-shaped inlet channel are: the angle between the two inlet channels is fixed at 60° and is symmetrical about the central straight line of the mixing channel, the inner diameter of the channel is 0.3-1 cm, the outer diameter is 0.5-1.2 cm, the length is 0.5-2 cm, and the outer shell wall thickness is 1 mm.

[0025] Wherein, the reaction temperature is 0-60°C, such as 20°C, 25°C, 30°C, 40°C.

[0026] The technical solution provided by the present invention solves the problems in the prior art that microreactors cannot be expanded for production and are prone to clogging, and that the PDI of continuous flow reactors is too large. The method for conducting organic catalytic ester exchange reaction in macro-microreactors provided by the present invention shortens the ester exchange reaction time and improves the conversion rate. The characteristic scale of the macro-microreactors reaches the centimeter level, which can achieve high-throughput synthesis.

[0027] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0028] (1) The present invention is based on macro-microreactors to enhance the enzymatic transesterification reaction process and rapidly and with high throughput prepare polymer molecular brushes.

[0029] (2) Compared with the traditional autoclave reactor, the macro-micro reactor of the present invention significantly shortens the reaction time, improves the conversion rate, reduces the molecular weight distribution, and increases the output. For example, the TBD-catalyzed caprolactone reaction time is increased from 60 min to 5 min, the conversion rate is increased from 14.9% to 95%, the molecular weight distribution is reduced from 1.6 to 1.05, and the output is increased from 0.169 g / min to 0.9747 g / min.

[0030] (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 of TBD-catalyzed caprolactone is increased from 2 ml / min to 5 ml / min, and the output per unit time is increased from 0.381 g / min to 0.9747 g / min.

[0031] (4) Compared with a continuous flow reactor (>2.0 mm without internal components), the present invention significantly shortens the reaction time, improves the conversion rate, and reduces the molecular weight distribution based on the macro-micro reactor. For example, the conversion rate of TBD-catalyzed caprolactone is increased from 87% to 95%, and the molecular weight distribution is reduced from 1.29 to 1.05. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] 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.

[0033] Figure 1 This is one of the overall structural schematic diagrams of the centimeter-level macro-micro reaction device of the present invention.

[0034] Figure 2 This is one of the overall structural schematic diagrams of the centimeter-level macro-micro reaction device of the present invention.

[0035] Figure 3 It is a schematic diagram of the internal components of the centimeter-scale macro-micro spiral macro-micro reactor of the present invention.

[0036] Figure 4 1HNMR chart of polycaprolactone of the examples.

[0037] Figure 5 1HNMR diagram of polyvalerolactone of Example.

[0038] Figure 6 1HNMR diagram of Example polypentadecalactone.

[0039] Figure 7 1HNMR diagram of poly(cyclohexylene tridecanedioate) according to the example.

[0040] Figure 8 This is the HNMR chart of the example polyoxycycloheptadeca-8-en-2-one. DETAILED DESCRIPTION

[0041] 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.

[0042] 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.

[0043] In the following examples of the present invention, the structure of the product was determined using a 400 MHz Bruker nuclear magnetic resonance instrument:

[0044] Take 10 mg of polymer molecular brush sample and put it into NMR tube, add deuterated chloroform, shake until it is completely dissolved and then measure the sample.

[0045] In the following embodiments of the present invention, the molecular weight and molecular weight distribution of the product are measured by the following method:

[0046] A Wyatt size exclusion chromatography system was used, equipped with an SSI 1500 pump, a Wyatt OptilabrEX detector, and a Waters Styragel HR GPC column for detection;

[0047] Analysis conditions: mobile phase was tetrahydrofuran, flow rate was 0.7 mL / min, column temperature was 35 °C, and polystyrene narrow distribution was used as standard.

[0048] Sample measurement: Take 5 mg of pure sample in a centrifuge tube, add 1 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.

[0049] In some embodiments, the microreactor device used is as follows Figure 1 As shown, it includes a first sample introduction device, a second sample introduction device, a Y-type mixer, a macro-micro reactor, and a receiver. The macro-micro reactor is provided with a heating device. The structural parameters of the Y-type inlet channel are: the angle between the two inlet channels is fixed at 60° and is symmetrical about the central straight line of the mixing channel, the inner diameter of the channel is 0.5 cm, the outer diameter is 1 cm, the length is 1.5 cm, and the outer shell wall thickness is 1 mm. The first sample introduction device and the second sample introduction device are connected to the Y-type mixer in parallel, and then connected in series with the macro-micro reactor and the receiver in sequence.

[0050] In some embodiments, the microreactor device used is as follows Figure 2 As shown, it includes a first sample injection device, a second sample injection device, a third sample injection device, a first mixer, a second mixer, a first macro-micro reactor, a second macro-micro reactor, and a receiver; the macro-micro reactor is provided with a heating device. The first sample injection device and the second sample injection device are connected to the first mixer in parallel, and then connected to the first macro-micro reactor in series; the first macro-micro reactor and the third sample injection device are connected to the second mixer in parallel, and then connected to the second macro-micro reactor and the receiver in series.

[0051] In the following examples, [M]0 is the concentration of the monomer.

[0052] The nuclear magnetic resonance of the products obtained in the following embodiments is as follows Figure 4-8 shown.

[0053] In some embodiments, the macro-microreactor is Figure 3 As shown, the specific production is as follows:

[0054] The internal components of the spiral macro-microreactor HSI (3-1-3) are formed by a circular cross-section along a spiral in the channel. The first value 3 represents the inner diameter of the reactor is 3 mm, the second value 3 represents the diameter of the copper wire added to the pipeline is 3 mm, and the third value 1 represents the pitch of the spiral copper wire is 1 mm.

[0055] The internal components of the serpentine macro-microreactor SSI-D-1 (3-0.5-1) are based on a straight line, and the straight line is twisted into a serpentine structure on the center plane. The placement direction (D1) is that the center plane of the SSI is parallel to the center planes of the inlet and outlet. The first value 3 represents the inner diameter of the reactor 3mm, the second value 0.5 represents the diameter of the helix 0.5mm, and the third value 1 represents the pitch 1mm.

[0056] The internal components of the serpentine macro-microreactor SSI-D-2 (3-0.5-1) are based on a straight line, which is twisted into a serpentine structure on the central plane. The placement direction (D2) is that the two planes are perpendicular to each other. The first value 3 represents the inner diameter of the reactor 3mm, the second value 0.5 represents the diameter of the spiral line 0.5mm, and the third value 1 represents the pitch 1mm.

[0057] The internal component of the O-shaped macro-microreactor OSI (3-1.5-3) is a copper wire circle. The first value 3 represents the inner diameter of the reactor is 3 mm, the second value 1.5 represents the diameter of the O-ring is 1.5, and the third value represents the distance between adjacent O-rings is 3 mm.

[0058] The internal components of the linear macro-microreactor SLSI (3-0.5) are straight copper wires. The first value 3 represents the inner diameter of the reactor, which is 3 mm, and the second value 1.5 represents the diameter of the spiral wire, which is 0.5 mm.

[0059] Table 1 Parameters of macro and micro reactors

[0060]

[0061] Example 1

[0062] In the macro-microreactor SLSI (3-0.5), the retention volume of the tube is 20 ml. The Schlenk apparatus is used to bake a 100 ml ampoule at high temperature and replace the gas three times. Lactide (4.32 g, 30 mmol, molecular weight 144) and dry toluene are added to the ampoule under argon environment to prepare 10 ml solution A; benzyl alcohol (3 mmol, 0.324 g, molecular weight 108.14), TBD (3 mmol, 0.416 g, molecular weight 139.2) are added, and dry toluene is prepared into 5 ml solution B; ([M]0 = 2 mol / L). Solution A and solution B are transferred to two 50 ml airtight syringes respectively. The prepared macro-microreactor is rinsed with anhydrous toluene to remove air and moisture in the reactor. Among them, the flow rate of injection pump A is 0.33 ml / min, the flow rate of injection pump B is 0.33 ml / min, and the total flow rate is 0.66 ml / min. The oil bath of the reaction pipeline device is heated to 30 ° C. The reaction time is 30 minutes, the product is collected after quenching, precipitated in cold methanol, and vacuum centrifuged and dried at room temperature for 48 hours to obtain a pure product. The monomer conversion rate of the organic catalytic ring-opening polymerization during the polymerization process is 77%, and the molecular weight and molecular weight distribution index of the polylactide are determined by GPC, with a number average molecular weight of 1100 g / mol, a molecular weight distribution index of 1.25, and a yield of 0.13 g / min.

[0063] Example 2

[0064] In the macro-microreactor OSI (3-1.5-3), the retention volume of the tube is 25 ml. The ampoule is baked at high temperature and the gas is replaced by using a Schlenk device. In an argon environment, pentad lactone (7.2 g, 30 mmol, molecular weight 240) and dry toluene are added to the ampoule to prepare 25 mL of solution A; phenylpropanol (2 mmol, 0.272 g, molecular weight 136.19), DPP (0.1 mmol, 0.0250 g, molecular weight 250.19), and dry toluene are added to prepare 25 mL of solution B, ([M]0 = 0.6 mol / L). Solution A and solution B are transferred to two 50 mL airtight syringes respectively. The prepared macro-microreactor is rinsed with anhydrous toluene to remove air and moisture in the reactor. Among them, the flow rate of injection pump A is 5 mL / min, the flow rate of injection pump B is 5 mL / min, and the total flow rate is 10 mL / min. The oil bath of the reaction pipeline device is heated to 30 ° C. The reaction time is 2.5 minutes, the product is collected after quenching, precipitated in cold methanol, and vacuum centrifuged and dried at room temperature for 48 hours to obtain a pure product. The monomer conversion rate of the organic catalytic ring-opening polymerization during the polymerization process is 20%, and the molecular weight and molecular weight distribution index of the polypentadecacyclic lactone are determined by GPC, with a number average molecular weight of 790 g / mol, a molecular weight distribution index of 1.4, and a yield of 0.259 g / min.

[0065] Example 3

[0066] In the macro-microreactor SSL-D1 (3-0.5-1), the retention volume of the tube is 5 ml. The ampoule is baked at high temperature and the gas is replaced using a Schlenk device. Tridecane dioic acid cyclohexyl ester (0.5407 g, 2 mmol, molecular weight 270) and dry tetrahydrofuran are added to the ampoule under an argon environment to prepare 10 mL of solution A; 5-hexene-1-ol (2 mmol, 0.200 g, molecular weight 100.16), DBU (0.2 mmol, 0.0304 g molecular weight 152.241), and dry tetrahydrofuran are added to prepare 10 mL of solution B, ([M]0 = 0.1 mol / L). Solution A and solution B are transferred to two 50 mL airtight syringes respectively. The prepared macro-microreactor is rinsed with anhydrous toluene to remove air and moisture in the reactor. Among them, the flow rate of injection pump A is 0.25mL / min, the flow rate of injection pump B is 0.25mL / min, and the total flow rate is 0.5mL / min. The reaction temperature is 90°C. The reaction time is 10min, the product is collected after quenching, precipitated in cold methanol, and vacuum centrifuged and dried at room temperature for 48h. The monomer conversion rate of organic catalytic ring-opening polymerization during the polymerization process is 90%, and the molecular weight and molecular weight distribution index of poly(cyclohexylene tridecanedioate) are determined by GPC, with a number average molecular weight of 350g / mol, a molecular weight distribution index of 1.7, and a yield of 0.0109g / min.

[0067] Example 4

[0068] Add 5-norbornene-exo-2,3-dicarboxylic anhydride (10 g, 61 mmol), 6-amino-1-hexanol (7.1 g, 61.0 mmol) and toluene (120 mL) to a 500 mL round-bottom flask and stir to mix. Build a Dean-Stark apparatus with a condenser. Heat the reaction to 120 ° C until the solution begins to reflux and react for 12 hours. Take a trace amount of the reaction solution, test the nuclear magnetic resonance hydrogen spectrum to show that the reaction conversion is complete, and then stop the heating reaction. 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 0.1 mol / L hydrochloric acid aqueous solution (50 mL) to extract three times, take the organic phase, and then use saturated salt water solution (50 mL) to extract once. The organic phase obtained by extraction is dried with anhydrous magnesium sulfate to remove residual moisture. The solvent was removed by a rotary evaporator to obtain a crude reaction product, which was dried in a vacuum drying oven for 12 h to obtain light yellow N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide, which was added with molecular sieves for later use.

[0069] In the macro-microreactor, HIS (10-3-10) was added, and the retention volume of the tube was 36 ml. The ampoule was baked at high temperature and the gas was replaced using a Schlenk device. Trimethylene carbonate (30.6 g, 300 mmol, molecular weight 102) and dry toluene were added to the ampoule under argon to prepare 35 mL of solution A; N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (1 mmol, 0.263 g, molecular weight 263), TBD (1 mmol, 0.1392 g, molecular weight 139.2) were added, and dry toluene was added to prepare 40 mL of solution B, ([M]0 = 4 mol / L). Solution A and solution B were transferred to two 50 mL airtight syringes respectively. The prepared macro-microreactor was rinsed with anhydrous toluene to remove air and moisture in the reactor. Among them, the flow rate of injection pump A is 15mL / min, the flow rate of injection pump B is 15mL / min, and the total flow rate is 30mL / min. The reaction temperature is 60°C. The reaction time is 1.2min. The product is collected after quenching, precipitated in cold methanol, and vacuum centrifuged and dried at room temperature for 48h. The monomer conversion rate of organic catalytic ring-opening polymerization during the polymerization process is 96%. The molecular weight and molecular weight distribution index of polytrimethylene carbonate are determined by GPC. The number average molecular weight is 29300g / mol, the molecular weight distribution index is 1.2, and the output is 10.57g / min.

[0070] Example 5

[0071] In the macro-microreactor SSL-D2 (3-0.5-1), the retention volume of the tube is 5 ml. The ampoule is baked at high temperature and the gas is replaced using a Schlenk device. Trimethylene carbonate (3.06 g, 30 mmol, molecular weight 102) and dry toluene are added to the ampoule under argon environment to prepare 25 mL of solution A; 5-hexen-1-ol (1 mmol, 0.1 g, molecular weight 100.159), TBD (1 mmol, 0.1392 g, molecular weight 139.2), and dry toluene are added to prepare 25 mL of solution B, ([M]0 = 0.6 mol / L). Solution A and solution B are transferred to two 50 mL gas-tight syringes respectively. The prepared macro-microreactor is rinsed with anhydrous toluene to remove air and moisture in the reactor. Among them, the flow rate of injection pump A is 0.5 mL / min, the flow rate of injection pump B is 1.5 mL / min, and the total flow rate is 2 mL / min. The reaction temperature is 60 ° C. The reaction time was 2.5 min. The product was collected after quenching, precipitated in cold methanol, and vacuum centrifuged and dried at room temperature for 48 h. The monomer conversion rate of the organic catalytic ring-opening polymerization during the polymerization process was 79%. The molecular weight and molecular weight distribution index of polytrimethylene carbonate were determined by GPC, with a number average molecular weight of 3300 g / mol, a molecular weight distribution index of 1.3, and a yield of 0.0807 g / min.

[0072] Example 6

[0073] In the macro-microreactor HSI (2-0.5-1), the retention volume of the tube is 25 ml. The ampoule is baked at high temperature and the gas is replaced using a Schlenk device. δ-valerolactone (2g 20mmol, molecular weight 100) and dry toluene are added to the ampoule under argon environment to prepare 10mL solution A; N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (2mmol, 0.526g), TBD (0.3mmol, 0.0416g, molecular weight 139.2) are added, and dry toluene is added to prepare 10mL solution B, ([M]0=1mol / L). Solution A and solution B are transferred to two 50mL airtight syringes respectively. The prepared macro-microreactor is rinsed with anhydrous toluene to remove air and moisture in the reactor. Among them, the flow rate of injection pump A is 3.5mL / min, and the flow rate of injection pump B is 3.5mL / min. The total flow rate was 7 mL / min. The reaction temperature was 25°C. The reaction time was 3.6 min. The product was collected after quenching, precipitated in cold methanol, and dried by vacuum centrifugation at room temperature for 48 h. The monomer conversion rate of the organic catalytic ring-opening polymerization during the polymerization process was 97%. The molecular weight and molecular weight distribution index of polyvalerolactone were determined by GPC, with a number average molecular weight of 2880 g / mol, a molecular weight distribution index of 1.07, and a yield of 0.611 g / min.

[0074] Example 7

[0075] In the macro-microreactor SSL-D2 (3-0.5-1), the retention volume of the tube was 25 ml. The ampoule was baked at high temperature and the gas was replaced using a Schlenk apparatus. δ-valerolactone (2 g 20 mmol, molecular weight: 100) was added to the ampoule under argon atmosphere. Dry toluene was added to make 10 mL and solution B 6-bromo-1-hexanol (2mmol, 0.526g molecular weight: 181.07), TBD (0.3mmol, 0.0416g molecular weight: 139.2), add dry toluene to make 10mL, ([M]0 = 1mol / L). Solution A and solution B are transferred to two 50mL airtight syringes respectively. The prepared macro-microreactor is rinsed with anhydrous toluene to remove air and moisture in the reactor. Among them, the flow rate of injection pump A is 3.5mL / min, the flow rate of injection pump B is 3.5mL / min, the total flow rate is 7mL / min, the reaction time is 7min, and the temperature is 0℃. The product is collected after quenching, precipitated in cold methanol, and vacuum centrifuged and dried at room temperature for 48h. The monomer conversion rate of organic catalytic ring-opening polymerization during the polymerization process is 20%. The molecular weight and molecular weight distribution index of polyvalerolactone are determined by GPC, and the number average molecular weight is 362g / mol, the molecular weight distribution index is 1.4, and the output is 0.126g / min.

[0076] Example 8

[0077] In the macro-microreactor HSI (2-0.5-1), the retention volume of the tube is 5 ml. The Schlenk device is used to bake a 100 mL ampoule at high temperature and replace the gas. Purified (Z)-oxocycloheptadec-8-ene-2-one (5.04 g, 20 mmol, molecular weight 252) and dry dichloromethane are added to the reaction bottle under argon environment to prepare 12.50 mL solution A; 3-butyn-1-ol (1 mmol, 0.0709 g, molecular weight 70.09), TBD (1 mmol, 0.1392 g, molecular weight 139.2) are added, and dry dichloromethane is prepared to prepare 12.5 mL solution B, ([M]0 = 0.8 mol / L). Solution A and solution B are transferred to two 50 mL gastight syringes respectively. The prepared macro-microreactor is rinsed with anhydrous toluene to remove oxygen and water in the pipeline. The flow rate of injection pump A is 0.25 mL / min, the flow rate of injection pump B is 0.25 mL / min, and the total flow rate is 0.5 mL / min. The reaction pipeline is ice-bathed to 0°C. The reaction residence time is 10 min. The reaction solution is collected and used 1The reaction conversion rate was calculated by H NMR to be 26%. 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 48 hours to obtain the product polyoxycycloheptadecan-8-ene-2-one, with a number average molecular weight of 1510 g / mol, a molecular weight distribution index of 1.6, and a yield of 0.0236 g / min.

[0078] Example 9

[0079] In the macro-microreactor HSI (3-1-3), the retention volume of the tube is 25 ml. The Schlenk apparatus is used to bake a 100 mL ampoule at high temperature and replace the gas. Purified ε-caprolactone monomer (11.4 g, 100 mmol, molecular weight 114 g) is added to the reaction bottle under argon environment, and dry toluene is added to prepare 25.0 mL solution A; N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (1 mmol, 0.2631 g, molecular weight 263), TBD (1 mmol, 0.1392 g, molecular weight 139.2), and anhydrous toluene are added to prepare 25 mL solution B ([M]0 = 2 mol / L). Solution A and solution B are transferred to two 50 mL gastight syringes respectively. The prepared macro-microreactor is rinsed with anhydrous toluene to remove oxygen and water in the pipeline. The flow rate of injection pump A is 2.5 mL / min, the flow rate of injection pump B is 2.5 mL / min, and the total flow rate is 5 mL / min. The reaction pipeline is heated to 30°C in a water bath. The reaction residence time is 5 min. The reaction liquid is collected and used 1 The reaction conversion rate calculated by H NMR reached 95%. 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 48 hours to obtain a polycaprolactone product with a number average molecular weight of 12500 g / mol, a molecular weight distribution index of 1.05, and a yield of 0.9747 g / min.

[0080] Example 10

[0081] In the macro-microreactor HSI (2-0.5-1), the retention volume of the tube is 5 ml. The Schlenk apparatus is used to bake a 100 mL ampoule at high temperature and replace the gas. Purified L-lactide monomer (14.4 g, 100 mmol, molecular weight: 144 g) is added to the reaction bottle under argon environment, and dry toluene is added to prepare 25 mL solution A; N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (1 mmol, 0.2631 g, molecular weight: 263)) and MTBD (1 mmol, 0.153 g, molecular weight: 153)) are added, and anhydrous toluene is added to prepare 25 mL solution B ([M]0 = 2 mol / L). Solution A and solution B are transferred to two 50 mL gastight syringes respectively. The prepared macro-microreactor is rinsed with anhydrous toluene to remove oxygen and water in the pipeline. The flow rate of injection pump A is 2.5 mL / min, the flow rate of injection pump B is 2.5 mL / min, the total flow rate is 5 mL / min, the reaction residence time is 1 min, and the reaction pipeline device is heated to 30°C in a water bath. The reaction residence time is 1 min. Collect the reaction solution and use 1 The reaction conversion rate was calculated by H NMR to be 90%. 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 48 hours to obtain a polylactide product with a number average molecular weight of 11660 g / mol, a molecular weight distribution index of 1.1, and a yield of 1.1664 g / min.

[0082] Embodiment 11

[0083] In the macro-microreactor SLSI (3-0.5), the retention volume of the tube is 5 ml. The Schlenk device is used to bake the 100 ml ampoule at high temperature and replace the gas three times. Lactide LA (4.32 g, 30 mmol, molecular weight 144) is added to the ampoule under argon environment and anhydrous dichloromethane is added to make 10 mL solution A; benzyl alcohol (3 mmol, 0.324 g, molecular weight 108.14), DMAP (1 mmol, 0.122 g molecular weight: 122) are added, and anhydrous dichloromethane is added to make 5 mL solution B ([M]0 = 2 mol / L), and solution A and solution B are transferred to two 50 mL gas-tight syringes respectively. The prepared macro-microreactor is rinsed with anhydrous toluene and anhydrous dichloromethane to remove air and moisture in the reactor. Among them, the flow rate of injection pump A is 0.25 mL / min, the flow rate of injection pump B is 0.25 mL / min, and the total flow rate is 0.5 mL / min. The reaction pipeline device oil bath is heated to 30°C. The reaction time is 10 minutes. The product is collected after quenching, precipitated in cold methanol, and vacuum centrifuged and dried at room temperature for 48 hours to obtain a pure product. Among them, the monomer conversion rate of the organic catalytic ring-opening polymerization during the polymerization process is 91%. The molecular weight and molecular weight distribution index of the polylactide are determined by GPC, and the number average molecular weight is 1290g / mol, the molecular weight distribution index is 1.21, and the output is 0.11g / min.

[0084] Example 12

[0085] In the two macro-microreactors HSI (3-1-3), the retention volume of the first macro-microreactor is 25 ml, and the retention volume of the second macro-microreactor is 1 ml. Using the Schlenk device, a 100 mL ampoule was baked at high temperature and the gas was replaced. Purified ε-caprolactone monomer (11.4 g, 100 mmol, molecular weight 114 g) was added to the reaction bottle under an argon environment, and dry toluene was added to prepare 25.0 mL solution A; benzyl alcohol (1 mmol, 0.1081 g, molecular weight 108.14), TBD (1 mmol, 0.1392 g, molecular weight 139.2) was added, and 24.8 ml of anhydrous toluene was added to prepare 25 mL solution B ([M] 0 = 2 mol / L); purified L-LA (L-lactide) (14.4 g, 100 mmol, molecular weight 144.13 g) and 12.86 ml of dry toluene were added to prepare 25.0 mL solution C. Solutions AC were transferred to three 50 mL airtight syringes respectively. Rinse the prepared macro-microreactor with anhydrous toluene to remove oxygen and water in the pipeline. The flow rate of injection pump A was 0.5 mL / min, the flow rate of injection pump B was 0.5 mL / min, the total flow rate was 1 mL / min, the temperature of the first reaction was 25 ° C, and the reaction residence time was 25 min. The flow rate of injection pump C was 0.5 mL / min, the reaction pipeline device was heated to 30 ° C in a water bath, and the reaction residence time of the second reaction was 0.6 min. Collect the reaction solution and use 1 The conversion rate was measured by H NMR, where the conversion rate of ε-caprolactone monomer reached 96%, and the conversion rate of L-LA monomer reached 97%. 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. During the synthesis process, it was placed in a vacuum drying oven and dried at room temperature for 48 hours to obtain the copolymer product PCL-g-PLLA, with a number average molecular weight of 24900g / mol, a molecular weight distribution index of 1.1, and a yield of 0.4324g / min.

[0086] Comparative Example 1

[0087] In a batch reactor, a 100 mL round-bottomed reaction bottle was baked at high temperature and the gas was replaced using a Schlenk device. Purified ε-caprolactone monomer (11.4 g, 100 mmol, molecular weight 114 g), N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (1 mmol, 0.2631 g, molecular weight 263), TBD (1 mmol, 0.1392 g, molecular weight 139.2), and anhydrous toluene were added to the reaction bottle to make a 50 mL reaction solution. The reaction mixture was then stirred under argon at 60 ° C. After reacting for 60 min, the product was collected and used 1The reaction conversion rate was calculated by HNMR, and the product was precipitated in cold methanol and then dried by vacuum centrifugation at room temperature for 48 hours to obtain a pure product. The monomer conversion rate of the organic catalytic ring-opening polymerization during the polymerization process was 14.9%, and the molecular weight and molecular weight distribution index of the polycaprolactone were determined by GPC, with a number average molecular weight of 11250 g / mol, a molecular weight distribution index of 1.6, and a yield of 0.169 g / min.

[0088] Comparative Example 2

[0089] In a microreactor with an inner diameter of 1 mm, the retention volume of the tube is 25 ml. The ampoule is baked at high temperature and the gas is replaced using a Schlenk device. Purified ε-caprolactone monomer (11.4 g, 100 mmol, molecular weight 114) is added to the reaction bottle under an argon environment, and dry toluene is added to prepare 25.0 mL of solution A; N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (1 mmol, 0.2631 g, molecular weight 263), TBD (1 mmol, 0.1392 g, molecular weight 139.2), and anhydrous toluene are added to prepare 25 mL of solution B. Use 25 mL of toluene to flush the pipeline to remove oxygen and water in the pipeline. The flow rate of injection pump A is 1 mL / min, the flow rate of injection pump B is 1 mL / min, the total flow rate is 2 mL / min, and the reaction residence time is 12.5 min. The reaction pipeline device is heated to 30°C in a water bath, and the reaction liquid is collected and used. 1 The reaction conversion rate was calculated by H NMR, and the product was precipitated in cold methanol and dried by vacuum centrifugation at room temperature for 48 hours to obtain a pure product. The monomer conversion rate of the organic catalytic ring-opening polymerization during the polymerization process was 93%, and the molecular weight and molecular weight distribution index of the polycaprolactone were determined by GPC, with a number average molecular weight of 12050 g / mol, a molecular weight distribution index of 1.1, and a yield of 0.381 g / min.

[0090] Comparative Example 3

[0091] In a continuous flow reactor with an inner diameter of 3 mm, the retention volume of the tube is 25 ml. The ampoule is baked at high temperature and the gas is replaced using a Schlenk device. Purified ε-caprolactone monomer (11.4 g, 100 mmol, molecular weight 114 g) is added to the reaction bottle under an argon environment, and dry toluene is added to prepare 25.0 mL of solution A; N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (1 mmol, 0.2631 g, molecular weight 263) and TBD (1 mmol, 0.1392 g, molecular weight 139.2) are added to anhydrous toluene to prepare 25 mL of solution B. Use 25 mL of toluene to flush the pipeline to remove oxygen and water in the pipeline. The flow rate of injection pump A is 2.5 mL / min, the flow rate of injection pump B is 2.5 mL / min, the total flow rate is 5 mL / min, the reaction residence time is 5 min, the reaction pipeline device is heated to 30 ° C in a water bath, the reaction liquid is collected, the reaction conversion rate is calculated using 1H NMR, and it is precipitated in cold methanol and vacuum centrifuged and dried at room temperature for 48 hours. A pure product is obtained. The monomer conversion rate of organic catalytic ring-opening polymerization during the polymerization process is 87%, and the molecular weight and molecular weight distribution index of polycaprolactone are determined by GPC. The number average molecular weight is 13200 g / mol, the molecular weight distribution index is 1.29, and the output is 0.89 g / min.

[0092] 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. Application of a macro-micro reactor in the preparation of degradable polyester, characterized in that: Cyclic monomers, initiators, catalysts and solvents are placed in macro- and micro-reactors for reaction to obtain degradable polyesters.

2. A method for preparing degradable polyester based on macro-micro reactor ring-opening polyester, characterized in that: Cyclic monomers, initiators, catalysts and solvents are placed in macro- and micro-reactors for reaction to obtain degradable polyesters.

3. The use according to claim 1 or the method according to claim 2, characterized in that: The monomers are ε-caprolactone, δ-valerolactone, trimethylene carbonate, lactide, pentadecyl lactone, cyclohexylene tridecanedioate, and (Z)-oxycycloheptadecan-8-ene-2-one.

4. The use according to claim 1 or the method according to claim 2, characterized in that: The monomer is any combination of ε-caprolactone, δ-valerolactone, trimethylene carbonate, lactide, pentadecacyclic lactone, cyclohexanediolate and (Z)-oxocycloheptadeca-8-ene-2-one; preferably, the catalyst is 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene, and / or 4-dimethylaminopyridine.

5. The use according to claim 1 or the method according to claim 2, characterized in that: The initiator is an alcohol, including benzyl alcohol, phenylpropanol, N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide, 5-hexen-1-ol, 3-butyn-1-ol, 6-bromo-1-hexanol; Preferably, the catalyst is 1,5,7-triazidobicyclo(4.4.0)dec-5-ene, diphenyl phosphate, 1,8-diazabicyclo[5.4.0]undec-7-ene; Preferably, the solvent for the reaction is tetrahydrofuran, toluene or dichloromethane.

6. The use according to claim 1 or the method according to claim 2, characterized in that: The ratio of the monomer to the catalyst is 10-300:1; Preferably, the monomer concentration is 0.1-4 mol / L; Preferably, the flow rate of the reaction is 0.5-30 mL / min.

7. The use according to claim 1 or the method according to claim 2, characterized in that: A monomer and a first solvent are made into a first solution, and an initiator, a catalyst, and a second solvent are made into a second solution; the first solution and the second solution are pumped into a macro-micro reactor respectively for reaction; Preferably, in the first solution, the concentration of the monomer is 0.1-10 mmol / mL; preferably, in the second solution, the concentration of the initiator is 0.02-1 mmol / mL.

8. The use according to claim 1 or the method according to claim 2, characterized in that: A first solution is prepared by a first monomer and a first solvent, a second solution is prepared by an initiator, a catalyst and a second solvent, and a third solution is prepared by a second monomer and a third solvent; the first solution and the second solution are respectively pumped into a first macro-micro reactor for a first reaction, and the first reaction effluent and the third solution are respectively pumped into a second macro-micro reactor for a second reaction; Preferably, in the first solution, the concentration of the first monomer is 0.1-10 mmol / mL; preferably, in the second solution, the concentration of the initiator is 0.02-1 mmol / mL; preferably, in the third solution, the concentration of the second monomer is 0.1-10 mmol / mL.

9. 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 component is 0.5-3 mm, and the pitch is 1-10 mm.

10. The use according to claim 1 or the method according to claim 2, characterized in that: The reaction temperature is 0-60°C, preferably 25°C, 30°C, 40°C.

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