A method for preparing biodegradable polyester based on organic ring-opening polymerization using macro / micro reactors

Abstract

This invention discloses a method for preparing biodegradable polyesters through organic ring-opening polymerization based on a macro-microreactor. The method involves reacting cyclic monomers, initiators, catalysts, and solvents in a macro-microreactor to obtain biodegradable polyesters. This invention is applicable to cyclic monomers and hydroxyl-containing initiators, and has a wide range of applicable substrates. Compared with traditional synthesis methods, the macro-microreactor, containing internal components and with characteristic dimensions reaching the centimeter scale, can significantly shorten the reaction time of organic catalytic transesterification, effectively improving the conversion rate while also enabling high-throughput synthesis. This invention provides a technical solution for the organic catalytic synthesis of new materials and shows great promise in this field.

Description

Technical Field

[0001] This invention relates to the field of cyclic monomer organic catalytic synthesis technology, specifically to a method for preparing biodegradable polyesters based on macro-microreactor organic ring-opening polymerization. Background Technology

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

[0003] Aliphatic polyester materials are currently extremely important biodegradable materials, possessing excellent biodegradability, biocompatibility, and mechanical strength, and are used in conduction systems, tissue engineering, and daily consumer goods. Ring-opening polymerization is currently most studied using metal catalysts, organic catalysts, and enzymes. However, metal catalysts are generally sensitive to water and air, making reaction conditions very harsh, and their use can lead to metal residues in the polymer, thus limiting their performance and applications. Organic catalysts can proceed under milder reaction conditions, avoiding metal residues in the polymer. For example, organic catalysts, such as DBU, generally have low catalytic activity and are only suitable for certain polyester systems, and often require large amounts. TBD is a highly active ring-opening polymerization catalyst; its catalyzed polymerization reaction is not only quite fast, but experimental results show that the polymerization process is controllable / active. However, transesterification during the reaction can cause the PDI (Polyester Intake Dispersion) range to become relatively wider.

[0004] Compared to batch reactors, microreactors, while offering enhanced mixing, heat transfer, and mass transfer in flow and good spatiotemporal control, still suffer from drawbacks such as low throughput, large pressure drop, and susceptibility to clogging. Macro-microreactors inherit the advantages of microreactors while overcoming these disadvantages. Therefore, this invention utilizes macro-microreactors for organic catalytic transesterification reactions, shortening the transesterification reaction time and increasing the conversion rate. With a characteristic scale reaching the centimeter level, macro-microreactors enable 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 biodegradable polyester based on organic ring-opening polymerization using a macro-micro reactor, which addresses the shortcomings of the existing technology.

[0006] To solve the above-mentioned technical problems, the present invention discloses the following technical solution:

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

[0008] Secondly, this invention discloses a method for preparing biodegradable polyester based on a macro-microreactor for ring-opening polyester, wherein cyclic monomers, initiators, catalysts, and solvents are placed in a macro-microreactor to react and obtain biodegradable polyester.

[0009] In the first and second aspects mentioned above,

[0010] The cyclic monomer is ε-caprolactone (a), δ-valerolactone (b), trimethylene carbonate (c), lactide (d), pentadecyl lactone (e), tridecanoic acid cycloethylene ester (f), (Z)-oxocycloheptadec-8-en-2-one (g), or any combination of the foregoing.

[0011]

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

[0013]

[0014] The catalysts include 1,5,7-triazine-bicyclo(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] The solvents used in the reaction are tetrahydrofuran, toluene, dichloromethane, etc.

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

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

[0019] 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, or 20 mL / min.

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

[0021] In some embodiments, a first monomer and a first solvent are prepared into a first solution, an initiator, a catalyst, and a second solvent are prepared into a second solution, and a second monomer and a third solvent are prepared into a third solution. The first solution and the second solution are respectively pumped into a first macro / microreactor to carry out a first reaction, and the effluent from the first reaction and the third solution are respectively pumped into a second macro / microreactor to carry out a second reaction. The first solvent, second solvent, and 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, or 1.5 mmol / mL. The concentrations of the initiator in the second solution are 0.02-1 mmol / mL, such as 0.04 mmol / mL, 0.08 mmol / mL, 0.1 mmol / mL, 0.2 mmol / mL, and 0.6 mmol / mL; the concentration of the second monomer in the third solution is 0.1-10 mmol / mL, such as 0.2 mmol / mL, 0.5 mmol / mL, 1 mmol / mL, 1.5 mmol / mL, 2 mmol / mL, 3 mmol / mL, 4 mmol / mL, and 5 mmol / mL.

[0022] The macro-microreactor includes a microchannel channel, and an internal component is disposed inside the microchannel channel. The retention volume of the macro-microreactor is 2-50 mL, such as 5 mL or 36 mL; the inner diameter of the microchannel channel 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 straight internal component; the spiral, serpentine, and O-shaped internal components have a pitch of 1-10 mm. In some embodiments, the internal component is made of copper.

[0023] The inner diameter of the macro-micro reactor 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 as follows: the included angle between the two inlet channels is fixed at 60° and is symmetrical about the center 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 wall thickness is 1 mm.

[0025] The reaction temperature is 0-60℃, such as 20℃, 25℃, 30℃, or 40℃.

[0026] The technical solution provided by this invention solves the problems of existing technologies, such as the inability of microreactors to scale up production and easy clogging, and the excessive PDI of continuous flow reactors. Based on the macro-microreactor provided by this invention, the method for organic catalytic transesterification reaction is to shorten the transesterification reaction time, improve the conversion rate, and achieve centimeter-level characteristic scale of macro-microreactors, enabling high-throughput synthesis.

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

[0028] (1) This invention is based on the enhancement of the enzymatic transesterification process by macro-micro reactors to rapidly and efficiently prepare polymer molecular brushes.

[0029] (2) Compared with traditional batch reactors, the present invention significantly shortens the reaction time, improves the conversion rate, reduces the molecular weight distribution, and increases the yield based on macro-micro reactors. For example, the reaction time of TBD-catalyzed caprolactone is reduced 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 yield is increased from 0.169 g / min to 0.9747 g / min.

[0030] (3) Compared with typical microreactors (characteristic scale = 1.0 mm), the present invention significantly increases the reaction flux based on macro-microreactors. For example, the flow rate of TBD-catalyzed caprolactone is increased from 2 ml / min to 5 ml / min, and the yield 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 a macro-micro reactor. For example, the conversion rate of caprolactone catalyzed by TBD is increased from 87% to 95%, and the molecular weight distribution is reduced from 1.29 to 1.05. Attached Figure Description

[0032] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments, and the advantages of the present invention in the above and / or other aspects will become clearer.

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

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

[0035] Figure 3 This 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 The image shows the 1H NMR spectrum of polycaprolactone in the example.

[0037] Figure 5 The image shows the 1H NMR spectrum of polyvalerone in the example.

[0038] Figure 6 The image shows the 1H NMR spectrum of polyvinylpyrrolidone in the example.

[0039] Figure 7 The image shows the 1H NMR spectrum of poly(tridecanoic acid cycloethylene ester) as an example.

[0040] Figure 8 The HNMR spectrum of polyoxycycloheptadec-8-en-2-one is shown in the example. Detailed Implementation

[0041] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0042] Unless otherwise specified, the experimental methods described in the following examples are conventional methods; the reagents and materials described are commercially available unless otherwise specified.

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

[0044] Take 10 mg of polymer molecular brush sample into an NMR tube, add deuterated chloroform, shake until 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 using the following methods:

[0046] The 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] Analytical conditions: The mobile phase was tetrahydrofuran, the flow rate was 0.7 mL / min, the column temperature was 35 °C, and the standard was polystyrene narrow distribution.

[0048] Sample measurement: Take 5 mg of pure sample into a centrifuge tube, add 1 mL of tetrahydrofuran solution to dilute, then filter using a disposable filter head (containing a 0.33 μm organic filter membrane), and take 0.4 mL of the solution for sample measurement.

[0049] In some embodiments, the microreactor device used is as follows: Figure 1 As shown, the system includes a first injection device, a second injection device, a Y-type mixer, a macro-microreactor, and a receiver. The macro-microreactor is equipped with a heating device. The structural parameters of the Y-type inlet channel are as follows: the included angle between the two inlet channels is fixed at 60° and symmetrical about the center 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 and second injection devices are connected in parallel to the Y-type mixer, and then connected in series with the macro-microreactor and the receiver.

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

[0051] In the following embodiments, [M]0 represents the concentration of the monomer.

[0052] The NMR spectra of the products obtained in the following embodiments are as follows: Figure 4-8 As shown.

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

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

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

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

[0057] The internal components of the O-ring macro-microreactor OSI(3-1.5-3) are copper wire rings. The first value 3 indicates that the inner diameter of the reactor is 3mm, the second value 1.5 indicates that the diameter of the O-ring is 1.5, and the third value indicates that the distance between adjacent O-rings is 3mm.

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

[0059] Table 1. Parameter values ​​of macro- and micro-reactors

[0060]

[0061] Example 1

[0062] In the SLSI (3-0.5) macro-microreactor, the retention volume of the tube was 20 mL. Using a Schlenk apparatus, 100 mL ampoules were heated to high temperature and the gas was purged three times. Under argon atmosphere, lactide (4.32 g, 30 mmol, molecular weight 144) and dried toluene were added to the ampoules to prepare 10 mL of solution A. Benzyl alcohol (3 mmol, 0.324 g, molecular weight 108.14), TBD (3 mmol, 0.416 g, molecular weight 139.2), and dried toluene were added to prepare 5 mL of solution B ([M]O = 2 mol / L). Solutions A and B were transferred to two 50 mL airtight syringes, respectively. The prepared macro-microreactor was rinsed with anhydrous toluene to remove air and moisture. The flow rate of syringe pump A was 0.33 mL / min, the flow rate of syringe pump B was 0.33 mL / min, and the total flow rate was 0.66 mL / min. The reaction tubing was heated to 30 °C in an oil bath. The reaction time was 30 min. The product was collected after quenching, precipitated in cold methanol, and vacuum centrifuged and dried at room temperature for 48 h to obtain a pure product. The monomer conversion rate of the organic-catalyzed ring-opening polymerization during the polymerization process was 77%. The molecular weight and molecular weight distribution index of polylactide were 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 was 25 mL. Using a Schlenk apparatus, the ampoules were heated to high temperature and purged with gas. Under argon atmosphere, pentadecyl lactone (7.2 g, 30 mmol, molecular weight 240) and dried toluene were added to the ampoules to prepare 25 mL of solution A. Additionally, phenylpropanol (2 mmol, 0.272 g, molecular weight 136.19), DPP (0.1 mmol, 0.0250 g, molecular weight 250.19), and dried toluene were added to prepare 25 mL of solution B ([M]O = 0.6 mol / L). Solutions A and B were transferred to two 50 mL airtight syringes, respectively. The prepared macro-microreactor was rinsed with anhydrous toluene to remove air and moisture. The flow rate of syringe pump A was 5 mL / min, the flow rate of syringe pump B was 5 mL / min, and the total flow rate was 10 mL / min. The reaction tubing was heated to 30 °C in an oil bath. 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 to obtain a pure product. The monomer conversion rate of the organic-catalyzed ring-opening polymerization during the polymerization process was 20%. The molecular weight and molecular weight distribution index of polypentadecanolactone were 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), with a retention volume of 5 mL, the ampoules were heated at high temperature and purged with gas using a Schlenk apparatus. Under argon atmosphere, cycloethylene tridecanoate (0.5407 g, 2 mmol, molecular weight 270) and dried tetrahydrofuran were added to the ampoules to prepare 10 mL solution A. Separately, 5-hexen-1-ol (2 mmol, 0.200 g, molecular weight 100.16), DBU (0.2 mmol, 0.0304 g, molecular weight 152.241), and dried tetrahydrofuran were added to prepare 10 mL solution B ([M]0 = 0.1 mol / L). Solutions A and B were transferred to two 50 mL airtight syringes, respectively. The prepared macro-microreactor was rinsed with anhydrous toluene to remove air and moisture from the reactor. The flow rates of syringe pump A and syringe pump B were both 0.25 mL / min, with a total flow rate of 0.5 mL / min. The reaction temperature was 90℃, and the reaction time was 10 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-catalyzed ring-opening polymerization during the polymerization process was 90%. The molecular weight and molecular weight distribution index of poly(tridecanoic acid cycloethylene ester) were determined by GPC, with a number-average molecular weight of 350 g / mol, a molecular weight distribution index of 1.7, and a yield of 0.0109 g / min.

[0067] Example 4

[0068] Add 10 g (61 mmol) of 5-norbornene-exo-2,3-dicarboxylic anhydride, 7.1 g (61.0 mmol) of 6-amino-1-hexanol, and 120 mL of toluene to a 500 mL round-bottom flask and stir to mix. Assemble a Dean-Stark apparatus with a condenser. Heat the reaction mixture to 120 °C until the solution begins to reflux, and react for 12 h. Take a small amount of the reaction mixture, and after the 1H NMR spectrum shows complete conversion, stop heating. Allow the reaction mixture to return to room temperature, then remove the solvent using a rotary evaporator. Dissolve the remaining product in 250 mL of dichloromethane. Extract three times with 50 mL of 0.1 mol / L hydrochloric acid solution, collecting the organic phase, followed by one extraction with 50 mL of saturated saline solution. Dry the extracted organic phase with anhydrous magnesium sulfate to remove residual moisture. The solvent was removed using a rotary evaporator to obtain the crude product of the reaction. The crude product was dried in a vacuum drying oven for 12 hours to obtain a pale yellow N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide, which was then added to a molecular sieve for later use.

[0069] In the macro-microreactor, HIS (10⁻³⁻¹⁰) was used, with a retention volume of 36 mL. Using a Schlenk apparatus, ampoules were heated to high temperature and purged with gas. Under argon atmosphere, trimethylene carbonate (30.6 g, 300 mmol, molecular weight 102) and dried toluene were added to the ampoules to prepare 35 mL of solution A. Additionally, 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), and dried toluene were added to prepare 40 mL of solution B ([M]O = 4 mol / L). Solutions A and B were transferred to two separate 50 mL airtight syringes. The prepared macro-microreactor was rinsed with anhydrous toluene to remove air and moisture. The flow rate of syringe pump A was 15 mL / min, the flow rate of syringe pump B was 15 mL / min, and the total flow rate was 30 mL / min. The reaction temperature was 60℃. The reaction time was 1.2 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 96%. The molecular weight and molecular weight distribution index of polytrimethylene carbonate were determined by GPC, with a number-average molecular weight of 29300 g / mol, a molecular weight distribution index of 1.2, and a yield of 10.57 g / min.

[0070] Example 5

[0071] In the macro-microreactor SSL-D2 (3-0.5-1), the retention volume of the tube was 5 mL. Using a Schlenk apparatus, the ampoules were heated to a high temperature and purged of gas. Under an argon atmosphere, trimethylene carbonate (3.06 g, 30 mmol, molecular weight 102) and dried toluene were added to the ampoules to prepare 25 mL of solution A. Separately, 5-hexen-1-ol (1 mmol, 0.1 g, molecular weight 100.159), TBD (1 mmol, 0.1392 g, molecular weight 139.2), and dried toluene were added to prepare 25 mL of solution B ([M]O = 0.6 mol / L). Solutions A and B were transferred to two separate 50 mL airtight syringes. The prepared macro-microreactor was rinsed with anhydrous toluene to remove air and moisture. The flow rate of syringe pump A was 0.5 mL / min, syringe pump B was 1.5 mL / min, and the total flow rate was 2 mL / min. The reaction temperature was 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 was 25 mL. Using a Schlenk apparatus, ampoules were heated at high temperature and purged with gas. Under argon atmosphere, δ-valerolactone (2 g, 20 mmol, molecular weight 100) and dried toluene were added to the ampoules to prepare 10 mL of solution A. Separately, N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (2 mmol, 0.526 g), TBD (0.3 mmol, 0.0416 g, molecular weight 139.2), and dried toluene were added to prepare 10 mL of solution B ([M]O = 1 mol / L). Solutions A and B were transferred to two 50 mL airtight syringes, respectively. The prepared macro-microreactor was rinsed with anhydrous toluene to remove air and moisture. The flow rate of syringe pump A was 3.5 mL / min, and the flow rate of syringe pump B was 3.5 mL / min. The total flow rate was 7 mL / min. The reaction temperature was 25℃. The reaction time was 3.6 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 organocatalytic ring-opening polymerization during the polymerization process was 97%. The molecular weight and molecular weight distribution index of polyvalerone 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. Using a Schlenk apparatus, the ampoules were heated at high temperature and purged with gas. Under an argon atmosphere, δ-valerolactone (2 g 20 mmol, molecular weight: 100) was added to the ampoules, and dried toluene was added to prepare 10 mL of solution B. 6-Bromo-1-hexanol (2 mmol, 0.526 g, molecular weight: 181.07) and TBD (0.3 mmol, 0.0416 g, molecular weight: 139.2) were added to dry toluene to prepare 10 mL ([M]0 = 1 mol / L). Solutions A and B were transferred to two 50 mL airtight syringes, respectively. The prepared macro-microreactor was rinsed with anhydrous toluene to remove air and moisture. The flow rate of syringe pump A was 3.5 mL / min, the flow rate of syringe pump B was 3.5 mL / min, the total flow rate was 7 mL / min, the reaction time was 7 min, and the temperature was 0 °C. 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 20%. The molecular weight and molecular weight distribution index of polyvalerate were determined by GPC, with a number-average molecular weight of 362 g / mol, a molecular weight distribution index of 1.4, and a yield of 0.126 g / min.

[0076] Example 8

[0077] In the macro-microreactor HSI(2-0.5-1), the retention volume of the tubes was 5 mL. Using a Schlenk apparatus, 100 mL ampoules were heated at high temperature and purged of gas. Under an argon atmosphere, purified (Z)-oxocycloheptadec-8-en-2-one (5.04 g, 20 mmol, molecular weight 252) and dry dichloromethane were added to prepare a 12.50 mL solution A. Separately, 3-butyn-1-ol (1 mmol, 0.0709 g, molecular weight 70.09), TBD (1 mmol, 0.1392 g, molecular weight 139.2), and dry dichloromethane were added to prepare a 12.5 mL solution B ([M]O = 0.8 mol / L). Solutions A and B were transferred to two 50 mL gas-tight syringes, respectively. The prepared macro-microreactor was rinsed with anhydrous toluene to remove oxygen and water from the tubes. The flow rate of syringe pump A was 0.25 mL / min, the flow rate of syringe pump B was 0.25 mL / min, and the total flow rate was 0.5 mL / min. The reaction tubing was kept in an ice bath at 0°C. The reaction residence time was 10 min. The reaction solution was collected and utilized... 1H NMR calculations showed a reaction conversion rate of 26%. The product was collected by precipitation with cold methanol and centrifugation. The precipitation was dissolved in solvent and centrifuged three times to thoroughly wash the product. The product was then dried in a vacuum drying oven at room temperature for 48 hours to obtain the product polyoxycyclic heptadecano-8-en-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 tubes was 25 mL. Using a Schlenk apparatus, 100 mL ampoules were heated at high temperature and purged of gas. Purified ε-caprolactone monomer (11.4 g, 100 mmol, molecular weight 114 g) was added to the reaction flask under argon atmosphere, followed by the addition of dried toluene to prepare 25.0 mL solution A. Separately, 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 prepare 25 mL solution B ([M]O = 2 mol / L). Solutions A and B were transferred to two 50 mL gas-tight syringes, respectively. The prepared macro-microreactor was rinsed with anhydrous toluene to remove oxygen and water from the tubes. The flow rate of syringe pump A was 2.5 mL / min, the flow rate of syringe pump B was 2.5 mL / min, and the total flow rate was 5 mL / min. The reaction tubing was heated to 30°C in a water bath. The reaction residence time was 5 min. The reaction solution was collected and utilized... 1 H NMR calculations showed a reaction conversion rate of 95%. The product was collected by precipitation with cold methanol and centrifugation. The process of dissolving the precipitate in solvent and centrifuging was repeated three times to thoroughly wash the product. The product was then dried in a vacuum drying oven at room temperature for 48 hours to obtain 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 tubes was 5 mL. Using a Schlenk apparatus, 100 mL ampoules were heated at high temperature and purged of gas. Purified L-lactide monomer (14.4 g, 100 mmol, molecular weight: 144 g) was added to the reaction flask under argon atmosphere, followed by the addition of dried toluene to prepare 25 mL of solution A. Separately, N-(6-hydroxyhexyl)-5-norbornene-2,3-exo-dicarboximide (1 mmol, 0.2631 g, molecular weight: 263), MTBD (1 mmol, 0.153 g, molecular weight: 153), and anhydrous toluene were added to prepare 25 mL of solution B ([M]O = 2 mol / L). Solutions A and B were transferred to two separate 50 mL airtight syringes. The prepared macro-microreactor was rinsed with anhydrous toluene to remove oxygen and water from the tubes. The flow rate of syringe pump A was 2.5 mL / min, the flow rate of syringe pump B was 2.5 mL / min, the total flow rate was 5 mL / min, the reaction residence time was 1 min, and the reaction tubing was heated to 30°C in a water bath for 1 min. The reaction solution was collected and utilized... 1 H NMR calculations showed a reaction conversion rate of 90%. The product was collected by precipitation with cold methanol and centrifugation. The process of dissolving the precipitate in solvent and centrifuging was repeated three times to thoroughly wash the product. The product was then dried in a vacuum drying oven at room temperature for 48 hours to obtain 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] Example 11

[0083] In the SLSI (3-0.5) macro-microreactor, the retention volume of the tube was 5 mL. Using a Schlenk apparatus, 100 mL ampoules were heated at high temperature and the gas was purged three times. Under argon atmosphere, lactide LA (4.32 g, 30 mmol, molecular weight 144) was added to the ampoules, and anhydrous dichloromethane was added to prepare 10 mL of solution A. Benzyl alcohol (3 mmol, 0.324 g, molecular weight 108.14) and DMAP (1 mmol, 0.122 g, molecular weight 122) were added, and anhydrous dichloromethane was added to prepare 5 mL of solution B ([M]O = 2 mol / L). Solutions A and B were transferred to two 50 mL airtight syringes, respectively. The prepared macro-microreactor was rinsed with anhydrous toluene and anhydrous dichloromethane to remove air and moisture. The flow rate of syringe pump A was 0.25 mL / min, the flow rate of syringe pump B was 0.25 mL / min, and the total flow rate was 0.5 mL / min. The reaction pipeline was heated to 30°C in an oil bath. The reaction time was 10 min. The product was collected after quenching, precipitated in cold methanol, and vacuum centrifuged and dried at room temperature for 48 h to obtain a pure product. The monomer conversion rate of the organic-catalyzed ring-opening polymerization during the polymerization process was 91%. The molecular weight and molecular weight distribution index of polylactide were determined by GPC, with a number-average molecular weight of 1290 g / mol, a molecular weight distribution index of 1.21, and a yield of 0.11 g / min.

[0084] Example 12

[0085] In two macro-microreactors HSI (3-1-3), the retention volume of the first macro-microreactor was 25 ml, and the retention volume of the second macro-microreactor was 1 ml. Using a Schlenk apparatus, 100 mL ampoules were heated at high temperature and purged with gas. Under an argon atmosphere, purified ε-caprolactone monomer (11.4 g, 100 mmol, molecular weight 114 g) was added to the reaction flask, and dried toluene was added to prepare 25.0 mL solution A. Benzyl alcohol (1 mmol, 0.1081 g, molecular weight 108.14) and TBD (1 mmol, 0.1392 g, molecular weight 139.2) were 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 dried toluene were added to prepare 25.0 mL solution C. Solutions A and C were transferred to three 50 mL airtight syringes, respectively. The prepared macro-microreactor was rinsed with anhydrous toluene to remove oxygen and water from the tubing. The flow rate of syringe pump A was 0.5 mL / min, the flow rate of syringe 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 syringe pump C was 0.5 mL / min, the reaction tubing was heated to 30 °C in a water bath, and the reaction residence time of the second reaction was 0.6 min. The reaction solution was collected and utilized... 1 The conversion rate was determined by ¹H NMR, with ε-caprolactone monomer conversion reaching 96% and L-LA monomer conversion reaching 97%. The product was collected by precipitation and centrifugation with cold methanol. The process of solvent dissolution and centrifugation was repeated three times to thoroughly wash the product. The product was then dried in a vacuum drying oven at room temperature for 48 hours to obtain the copolymer PCL-g-PLLA, with a number average molecular weight of 24900 g / mol, a molecular weight distribution index of 1.1, and a yield of 0.4324 g / min.

[0086] Comparative Example 1

[0087] In a batch reactor, using a Schlenk apparatus, a 100 mL round-bottom reaction flask was heated at high temperature and purged with gas. Under argon atmosphere, 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 flask to prepare a 50 mL reaction solution. The reaction mixture was then stirred under argon atmosphere at 60 °C. After reacting for 60 min, the product was collected and processed using... 1The reaction conversion rate was calculated by HNMR, and the product was precipitated in cold methanol and then vacuum centrifuged and dried at room temperature for 48 h to obtain a pure product. The monomer conversion rate of the organocatalytic ring-opening polymerization during the polymerization process was 14.9%. The molecular weight and molecular weight distribution index of 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 was 25 mL. Using a Schlenk apparatus, the ampoules were heated at high temperature and purged of gas. Purified ε-caprolactone monomer (11.4 g, 100 mmol, molecular weight 114) was added to the reaction flask under argon atmosphere, followed by the addition of dried toluene to prepare a 25.0 mL solution A. Separately, 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 prepare a 25 mL solution B. The tubing was flushed with 25 mL of toluene to remove oxygen and water. The flow rate of syringe pump A was 1 mL / min, the flow rate of syringe pump B was 1 mL / min, the total flow rate was 2 mL / min, the reaction residence time was 12.5 min, and the reaction tubing was heated to 30 °C in a water bath. The reaction solution was collected and used for… 1 The reaction conversion rate was calculated by ¹H NMR, and the product was precipitated in cold methanol and dried under vacuum centrifugation at room temperature for 48 h to obtain a pure product. The monomer conversion rate of the organic-catalyzed ring-opening polymerization during the polymerization process was 93%. The molecular weight and molecular weight distribution index of 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 was 25 mL. Using a Schlenk apparatus, the ampoules were heated at high temperature and purged with gas. Purified ε-caprolactone monomer (11.4 g, 100 mmol, molecular weight 114 g) was added to the reaction flask under an argon atmosphere, and dry toluene was added to prepare a 25.0 mL solution A. Separately, 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) were added, and anhydrous toluene was added to prepare a 25 mL solution B. The tubing was flushed with 25 mL of toluene to remove oxygen and water. The flow rate of syringe pump A was 2.5 mL / min, the flow rate of syringe pump B was 2.5 mL / min, the total flow rate was 5 mL / min, the reaction residence time was 5 min, the reaction tubing was heated to 30 °C in a water bath, the reaction solution was collected, the reaction conversion rate was calculated using 1H NMR, the product was precipitated in cold methanol, and vacuum centrifuged and dried at room temperature for 48 h to obtain a pure product. The monomer conversion rate of the organocatalytic ring-opening polymerization during the polymerization process was 87%. The molecular weight and molecular weight distribution index of polycaprolactone were determined by GPC, with a number-average molecular weight of 13200 g / mol, a molecular weight distribution index of 1.29, and a yield of 0.89 g / min.

[0092] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. Use of a macro-micro reactor for the preparation of a degradable polyester, characterized in that, The cyclic 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 respectively pumped into a macro-micro reactor to perform a reaction to obtain a degradable polyester; the cyclic monomer is ε-caprolactone, δ-valerolactone, trimethylene carbonate, lactide, pentadecalactone, cyclohexene ester of tridecanedioic acid, (Z)-oxocycloheptadec-8-en-2-one, or a combination of any of the foregoing. Or, The first monomer and the first solvent are made into a first solution, the initiator, the catalyst, and the second solvent are made into a second solution, and the second monomer and the third solvent are made into a third solution; the first solution and the second solution are respectively pumped into a first macro-micro reactor to perform a first reaction, and the first reaction effluent and the third solution are respectively pumped into a second macro-micro reactor to perform a second reaction; the first monomer and the second monomer are different monomers, and the monomers are ε-caprolactone, δ-valerolactone, trimethylene carbonate, lactide, pentadecalactone, cyclohexene ester of tridecanedioic acid, (Z)-oxocycloheptadec-8-en-2-one, or a combination of any of the foregoing. The macro-micro reactor comprises a micro-channel pipeline, and an inner member is arranged in the micro-channel pipeline; the inner member is a helical inner member, a snake-shaped inner member, an O-shaped inner member, or a straight-line inner member; the inner diameter of the micro-channel pipeline is 1-10 mm; and the diameter of the inner member is 0.5-3 mm.

2. Use according to claim 1, characterized in that, The catalyst is 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene and / or 4-dimethylaminopyridine.

3. Use according to claim 1, characterized in that, The initiator is an alcohol, including benzyl alcohol, phenylpropanol, N-(6-hydroxyhexyl)-5-norbornene-2,3-external-diformamide, 5-hexene-1-ol, 3-butyn-1-ol, and 6-bromo-1-hexanol.

4. The use according to claim 1, characterized in that, The catalyst is 1,5,7-triazobicyclo(4.4.0)dec-5-ene, diphenyl phosphate, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

5. The use according to claim 1, characterized in that, The solvent for the reaction is tetrahydrofuran, toluene, and dichloromethane.

6. The use according to claim 1, characterized in that, The ratio of the monomer to the catalyst is 10-300:

1.

7. Use according to claim 1, characterized in that, The concentration of the monomer is 0.1-4 mol / L.

8. The use according to claim 1, characterized in that, The flow rate of the reaction is 0.5-30 mL / min.

9. The use according to claim 1, characterized in that, In the first solution, the concentration of the monomer is 0.1-10 mmol / mL; and in the second solution, the concentration of the initiator is 0.02-1 mmol / mL.

10. The use according to claim 1, characterized in that, In the first solution, the concentration of the first monomer is 0.1-10 mmol / mL; in the second solution, the concentration of the initiator is 0.02-1 mmol / mL; and in the third solution, the concentration of the second monomer is 0.1-10 mmol / mL.

11. The use according to claim 1, characterized in that, The inner diameter of the macro-micro reactor is 1-10 mm, the diameter of the helical inner member is 0.5-3 mm, and the pitch is 1-10 mm.

12. The use according to claim 1, characterized in that, The temperature of the reaction is 0-60°C.

13. The use according to claim 1, characterized in that, The temperature of the reaction is 25°C, 30°C, or 40°C.

14. A method of making a degradable polyester based on a macro-micro reactor ring-opening polyester, characterized in that, The cyclic 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 respectively pumped into a macro-micro reactor to perform a reaction to obtain a degradable polyester; the cyclic monomer is ε-caprolactone, δ-valerolactone, trimethylene carbonate, lactide, pentadecalactone, cyclohexene ester of tridecanedioic acid, (Z)-oxocycloheptadec-8-en-2-one, or a combination of any of the foregoing; Or, The first monomer and the first solvent are made into a first solution, the initiator, the catalyst, and the second solvent are made into a second solution, and the second monomer and the third solvent are made into a third solution; the first solution and the second solution are respectively pumped into a first macro-micro reactor to perform a first reaction, and the first reaction effluent and the third solution are respectively pumped into a second macro-micro reactor to perform a second reaction; the first monomer and the second monomer are different monomers, and the monomers are ε-caprolactone, δ-valerolactone, trimethylene carbonate, lactide, pentadecalactone, cyclohexene ester of tridecanedioic acid, (Z)-oxocycloheptadec-8-en-2-one, or a combination of any of the foregoing; The macro-micro reactor comprises a micro-channel pipeline, and an inner member is arranged in the micro-channel pipeline; the inner member is a helical inner member, a snake-shaped inner member, an O-shaped inner member, or a straight-line inner member; the inner diameter of the micro-channel pipeline is 1-10 mm; and the diameter of the inner member is 0.5-3 mm.

15. The method of claim 14, wherein, The catalyst is 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene, and / or 4-dimethylaminopyridine, or the catalyst is 1,5,7-triazabicyclo(4.4.0)dec-5-ene, diphenyl phosphate, 1,8-diazabicyclo[5.4.0]undec-7-ene; The initiator is an alcohol, including benzyl alcohol, phenylpropanol, N-(6-hydroxyhexyl)-5-norbornene-2,3-external-diformylidene, 5-hexene-1-ol, 3-butyn-1-ol, 6-bromo-1-hexanol; The solvent of the reaction is tetrahydrofuran, toluene, dichloromethane.

16. The method of claim 14, wherein, The ratio of the monomer to the catalyst is 10-300:1; the monomer concentration is 0.1-4 mol / L; and the flow rate of the reaction is 0.5-30 mL / min.

17. The method of claim 14, wherein, In the first solution, the concentration of the monomer is 0.1-10 mmol / mL; in the second solution, the concentration of the initiator is 0.02-1 mmol / mL; or, in the first solution, the concentration of the first monomer is 0.1-10 mmol / mL; in the second solution, the concentration of the initiator is 0.02-1 mmol / mL; and in the third solution, the concentration of the second monomer is 0.1-10 mmol / mL.

18. The method of claim 14, wherein, The inner diameter of the macro-micro reactor is 1-10 mm, the diameter of the helical inner member is 0.5-3 mm, and the pitch is 1-10 mm.

19. The method of claim 14, wherein, The temperature of the reaction is 0-60 ℃.

20. The method of claim 14, wherein, The temperature of the reaction is 25 ℃, 30 ℃, or 40 ℃.

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