Method for preparing polyglycolic acid by direct esterification method

Abstract

The invention discloses a method for preparing polyglycolic acid by a direct esterification method, and belongs to the technical field of high polymer materials. According to the method disclosed by the invention, in the process of preparing the polyglycolic acid by a direct esterification method, according to the vapor pressure difference of different substances in a reactor, by controlling the temperature and the pressure in the reactor and controlling the reaction time within a certain range, the escape amount of the glycolide is effectively reduced, and the residual amount of a catalyst in the by-product glycolide is reduced to 0; on the premise that the quality of a polyglycolic acid product is not affected, the by-product glycolide is reused in the technological process of preparing the polyglycolic acid, and continuous production with high polyglycolic acid yield is achieved.

Description

Technical Field

[0001] This invention relates to the field of polymer materials technology, specifically to a method for preparing polyglycolic acid by direct esterification. Background Technology

[0002] Polyglycolic acid (PGA) has excellent biocompatibility, mechanical properties, high barrier properties, and high load deformation temperature. It is a rare biodegradable engineering polymer material with biodegradability similar to that of natural cellulose, and meets the requirements of industrial composting, household composting, and seawater degradation.

[0003] Currently, industrially viable methods for synthesizing polyglycolic acid (PGA) include direct polycondensation and glycolide ring-opening polymerization. The direct polycondensation of glycolic acid to PGA is simpler and lower in cost than glycolide ring-opening polymerization, making it more suitable for large-scale production. However, this method is generally reported to have low yields. This is because a large amount of the byproduct glycolide is extracted under high vacuum during the later stages of the polycondensation reaction, leading to a reduced yield. In the direct esterification process for PGA preparation, effectively reducing the amount of glycolide released through process control is an effective way to improve PGA yield. Furthermore, residual catalyst in glycolide can cause color deterioration in the PGA product, and excessive catalyst residue can accelerate PGA degradation. A more serious problem is that residual catalyst in glycolide requires each reuse to measure the catalyst content and recalculate the required catalyst input, resulting in excessive variability in process conditions, making it difficult to stabilize and meet the needs of continuous production. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing polyglycolic acid by direct esterification. In the process of preparing polyglycolic acid by direct esterification, this method can effectively reduce the amount of glycolide escaping by controlling the temperature and pressure in the reactor and keeping the reaction time within a certain range, based on the difference in vapor pressure of different substances in the reactor, and reduce the catalyst residue in the by-product glycolide to zero. Furthermore, without affecting the quality of the polyglycolic acid product, the by-product glycolide can be recycled into the process of preparing polyglycolic acid, thus realizing continuous production with high polyglycolic acid yield.

[0005] This invention first provides a method for preparing polyglycolic acid by direct esterification, comprising the following steps: (1) Glycolic acid or methyl glycolate is mixed with a catalyst and reacted to obtain polyglycolic acid oligomers; (2) Mix the polyglycolic acid oligomer with antioxidants and stabilizers, raise the system temperature to 200-230℃, and react under vacuum of 1500-1000 Pa for 0.5-2 h (the rough vacuum at this stage is mainly to increase the degree of polymerization of the oligomer and reduce the high vacuum polycondensation time in the later stage; the longer the polycondensation time, the more glycolide is generated); control the vacuum at 1000-500 Pa and continue the reaction for 0.5-2 h (at this vacuum, less glycolide is produced, and most of it is returned to the system to continue to participate in the reaction, which can effectively improve the product yield); reduce the vacuum to below 90 Pa and continue the reaction for 0.5-2 h (at this stage, more glycolide is produced, part of which is extracted and condensed into solid in the collector, and the other part is returned to the system to continue to participate in the reaction), to obtain polyglycolic acid crystalline polymer; (3) The polyglycolic acid crystalline polymer is subjected to solid-phase polycondensation reaction to obtain the polyglycolic acid.

[0006] In the above method, the catalyst is one or more of titanium tetrachloride, stannous octoate, stannous chloride, tetrabutyl titanate, and titanium dioxide; The molar ratio of glycolic acid or methyl glycolate to the catalyst is 13-25 mol:1 mmol; specifically, it can be 20 mol:1 mmol or 16.7 mol:1 mmol. The antioxidant is one or more of pentaerythritol tetra(bis-tert-butylhydroxyhydrogenated cinnamic acid) ester (Antioxidant 1010), α-tocopherol, 5-tert-butyl-4-hydroxy-2-methylphenyl sulfide (Antioxidant 300), and 2-tert-butyl-6-(3-tert-butyl-2-hydroxy-5-methylphenyl)methyl-4-methylphenyl acrylate (TH-330); The antioxidant is present in an amount of 50-250 ppm of the glycolic acid or methyl glycolate; specifically, it can be 70 ppm, 90 ppm, or 155 ppm. The stabilizing agent is one or more of the following: bis(2,4-di-tert-butylphenyl)pentaerythritol diphosphite (THP-24), diphenyl phosphite, triphenyl phosphite (TPP), triethyl phosphate (TEP), tris(2,4-di-tert-butylphenyl) phosphite (Antioxidant 168), N,N-bis(n-octadecane)hydroxylamine (Revonox 420), and 2-(2-hydroxy-3-tert-butyl-5-methylbenzyl)-4-methyl-6-tert-butylphenyl acrylate (IRGANOX 3052); The mass of the stabilizing agent is 60-230 ppm of the mass of the glycolic acid or methyl glycolate; specifically, it can be 75 ppm, 100 ppm or 140 ppm.

[0007] In the above method, step (1) involves mixing glycolic acid or methyl glycolate with a catalyst, heating to 170-220℃ (specifically 190℃) and reacting at atmospheric pressure for 0.5-2 h (specifically 0.5 h) until no more distillate is distilled out. The system is then subjected to a rough vacuum of 3000-2000 Pa (specifically 3000 Pa) and the reaction continues for another 0.5-2 h until the theoretical water yield reaches over 98%, thus obtaining the polyglycolic acid oligomer. In step (3), the temperature of the solid-phase polycondensation reaction is 195-210℃; the time of the solid-phase polycondensation reaction is 10-35 h.

[0008] The above method, in step (3), also includes the step of cutting the polyglycolic acid crystal polymer into granules and drying them under vacuum or forced air conditions at 100-120°C to remove water; and then carrying out solid-phase polycondensation reaction.

[0009] This invention also provides a semi-continuous preparation method for polyglycolic acid, comprising the following steps: S1. Glycolic acid or methyl glycolate is mixed with a catalyst and reacted to obtain polyglycolic acid oligomers. S2. Mix the polyglycolic acid oligomer with antioxidants and stabilizers, raise the system temperature to 200-230℃, and react under a vacuum of 1500-1000 Pa for 0.5-2 h; then, control the vacuum at 1000-500 Pa and continue the reaction for 0.5-2 h; finally, reduce the vacuum to below 90 Pa and continue the reaction for 0.5-2 h to obtain a crystalline polyglycolic acid polymer; and collect the byproducts, polyglycolic acid oligomer and glycolide, during this process. S3. The polyglycolic acid crystalline polymer is subjected to a solid-state polycondensation reaction to obtain the polyglycolic acid; S4. The by-product polyglycolic acid oligomer collected in step S2 is mixed with glycolide and glycolic acid or methyl glycolate as the starting material for the reaction, and steps S1-S3 are repeated. S5. Repeat step S4 multiple times.

[0010] In the semi-continuous preparation method described above, in step S1, the catalyst is one or more of titanium tetrachloride, stannous octoate, stannous chloride, tetrabutyl titanate, and titanium dioxide. The molar ratio of glycolic acid or methyl glycolate to the catalyst is 13-25 mol:1 mmol; specifically, it can be 20 mol:1 mmol or 16.7 mol:1 mmol. In step S2, the antioxidant is one or more of pentaerythritol tetra(bis-tert-butylhydroxyhydrocinnamic acid) ester (Antioxidant 1010), α-tocopherol, 5-tert-butyl-4-hydroxy-2-methylphenyl sulfide (Antioxidant 300), and 2-tert-butyl-6-(3-tert-butyl-2-hydroxy-5-methylphenyl)methyl-4-methylphenyl acrylate (TH-330); The antioxidant is present in an amount of 50-250 ppm of the glycolic acid or methyl glycolate; specifically, it can be 70 ppm, 90 ppm, or 155 ppm. The stabilizing agent is one or more of the following: bis(2,4-di-tert-butylphenyl)pentaerythritol diphosphite (THP-24), diphenyl phosphite, triphenyl phosphite (TPP), triethyl phosphate (TEP), tris(2,4-di-tert-butylphenyl) phosphite (Antioxidant 168), N,N-bis(n-octadecane)hydroxylamine (Revonox 420), and 2-(2-hydroxy-3-tert-butyl-5-methylbenzyl)-4-methyl-6-tert-butylphenyl acrylate (IRGANOX 3052); The mass of the stabilizing agent is 60-230 ppm of the mass of the glycolic acid or methyl glycolate; specifically, it can be 75 ppm, 100 ppm or 140 ppm.

[0011] In the semi-continuous preparation method described above, step S1 involves mixing glycolic acid or methyl glycolate with a catalyst, heating to 170-220℃ (specifically 190℃), and reacting at atmospheric pressure for 0.5-2 h (specifically 0.5 h) until no more distillate is distilled off. The system is then subjected to a rough vacuum of 3000-2000 Pa (specifically 3000 Pa) and the reaction continues for another 0.5-2 h until the theoretical water yield reaches over 98%, thus obtaining the polyglycolic acid oligomer. In step S3, the temperature of the solid-state polycondensation reaction is 195-210℃; the time of the solid-state polycondensation reaction is 10-35 h.

[0012] In the semi-continuous preparation method described above, step S3 further includes cutting the polyglycolic acid crystalline polymer into granules and drying them under vacuum or forced air conditions at 100-120°C to remove water; then a solid-phase polycondensation reaction is carried out.

[0013] In the semi-continuous preparation method described above, in step S4, the mass of the catalyst is one ten-thousandth to one thousandth of the mass of the glycolic acid; The antioxidant is 50-250 ppm of the total mass of the byproduct polyglycolic acid oligomer, glycolide, and glycolic acid or methyl glycolate; specifically, it can be 70 ppm, 90 ppm, or 155 ppm. The mass of the stabilizing agent is 60-230 ppm of the total mass of the byproduct polyglycolic acid oligomer, glycolide, and glycolic acid or methyl glycolate; specifically, it can be 75 ppm, 100 ppm, or 140 ppm.

[0014] In the semi-continuous preparation method described above, step S5 involves repeating step S4 2-10 times.

[0015] The glycolide and oligomers collected by the method of the present invention have a metal element content of 0 as determined by ICP analysis. They can be directly used as raw materials for PGA synthesis, which reduces the risk of catalyst stacking to continuous production, effectively reduces glycolide distillation, and significantly improves PGA polymerization yield. Detailed Implementation

[0016] The present invention will be further described in detail below with reference to specific embodiments. The embodiments given are only for illustrating the present invention and are not intended to limit the scope of the present invention.

[0017] Unless otherwise specified, the experimental methods described in the following examples are conventional methods.

[0018] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0019] Example 1 First stage: 100 mol glycolic acid and 5 mmol stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then increased to 3000 Pa and the reaction was continued for 1 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added to the system, and the system temperature was increased to 220 °C and the reaction was carried out at 1000 Pa for 1 h. The vacuum degree was controlled at 500 Pa and the reaction was continued for 1 h. The vacuum degree was reduced to below 70 Pa and the reaction was continued for 1 h to obtain a white PGA crystalline polymer with a number average molecular weight of 47000 Da. The PGA crystalline polymer obtained by melting was cut into granules and dried under vacuum at 100-120℃ to remove water, thus obtaining PGA granules. The PGA granules were then fed into a ZG-30L vacuum drum reactor manufactured by Yangzhou Ruibang Chemical Technology Co., Ltd. for solid-phase polycondensation at a temperature of 195℃ for 20 h, resulting in white PGA solid granules. The amount of glycolide and oligomers collected was 630 g.

[0020] Phase Two: During the polymerization process, the collected PGA oligomers and glycolide were analyzed by ICP, and the tin content was found to be 0%, indicating no catalyst residue in the glycolide and oligomers. 630 grams of the collected PGA oligomers and glycolide were mixed with 1575 grams of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated to obtain a white solid PGA material. In this step, the amounts of antioxidants and stabilizers were calculated based on the total mass of the PGA oligomers, glycolide, and glycolic acid.

[0021] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times.

[0022] Example 2 First stage: 100 mol glycolic acid and 5 mmol stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then increased to 3000 Pa and the reaction was continued for 1 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added to the system. The system temperature was increased to 220 °C and the reaction was carried out at 1500 Pa for 1 h. The vacuum degree was controlled at 900 Pa and the reaction was continued for 1 h. The vacuum degree was reduced to below 90 Pa and the reaction was continued for 1.5 h to obtain a white PGA crystalline polymer with a number average molecular weight of 46000 Da. The PGA crystalline polymer obtained by melting was cut into granules and dried under vacuum at 100-120℃ to remove water, thus obtaining PGA granules. The PGA granules were then fed into a vacuum drum reactor for solid-phase polycondensation at a temperature of 195℃ for 20 h, resulting in white PGA solid material. The amount of glycolide and oligomers collected was 710 g.

[0023] Phase Two: During the polymerization process, the collected PGA oligomers and glycolide were analyzed by ICP, and the tin content was found to be 0%, indicating no catalyst residue in the glycolide and oligomers. 710 grams of the collected PGA oligomers and glycolide were mixed with 1775 grams of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated to obtain a white PGA solid. In this step, the amounts of antioxidants and stabilizers were calculated based on the total mass of the PGA oligomers, glycolide, and glycolic acid.

[0024] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times.

[0025] Example 3 First stage: 100 mol glycolic acid and 5 mmol stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then increased to 3000 Pa and the reaction was continued for 1 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added to the system. The system temperature was increased to 220 °C and the reaction was carried out at 1250 Pa for 1 h. The vacuum degree was controlled at 750 Pa and the reaction was continued for 1 h. The vacuum degree was reduced to below 80 Pa and the reaction was continued for 1.5 h to obtain a white PGA crystalline polymer with a number average molecular weight of 48000 Da. The PGA crystalline polymer obtained by melting was cut into granules and dried under vacuum at 100-120℃ to remove water, thus obtaining PGA granules. The PGA granules were then fed into a vacuum drum reactor for solid-phase polycondensation at a temperature of 195℃ for 20 h, resulting in white PGA solid material. The amount of glycolide and oligomers collected was 680 g.

[0026] Phase Two: ICP analysis of the collected PGA oligomers and glycolide during the polymerization process showed a tin content of 0%, indicating no catalyst residue in the glycolide and oligomers. 680 grams of the collected PGA oligomers and glycolide were mixed with 1700 grams of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated to obtain a white solid PGA material. In this step, the amounts of antioxidants and stabilizers were calculated based on the total mass of the PGA oligomers, glycolide, and glycolic acid.

[0027] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times.

[0028] Example 4 First stage: 100 mol glycolic acid and 5 mmol stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C, and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then increased to 3000 Pa, and the reaction was continued for 2 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added to the system. The system temperature was increased to 230 °C, and the reaction was carried out at 1250 Pa for 0.5 h. The vacuum degree was controlled at 750 Pa, and the reaction was continued for 1.5 h. The vacuum degree was then reduced to below 80 Pa, and the reaction was continued for 0.5 h to obtain a white PGA crystalline polymer with a number average molecular weight of 49100 Da. The PGA crystalline polymer obtained by melting was cut into granules and dried under vacuum at 100-120℃ to remove water, thus obtaining PGA granules. The PGA granules were then fed into a vacuum drum reactor for solid-phase polycondensation at a temperature of 195℃ for 20 h, resulting in white PGA solid material. The amount of glycolide and oligomers collected was 685 g.

[0029] Phase Two: ICP analysis of the collected PGA oligomers and glycolide during the polymerization process showed a tin content of 0%, indicating no catalyst residue in the glycolide and oligomers. 685 grams of the collected PGA oligomers and glycolide were mixed with 1700 grams of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated. A white PGA solid was obtained. In this step, the amounts of antioxidants and stabilizers were calculated based on the total mass of the PGA oligomers, glycolide, and glycolic acid.

[0030] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times.

[0031] Example 5 First stage: 100 mol glycolic acid and 5 mmol stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then increased to 3000 Pa and the reaction was continued for another 1.5 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added to the system. The system temperature was increased to 220 °C and the reaction was carried out at 1250 Pa for 1.5 h. The vacuum degree was controlled at 750 Pa and the reaction was continued for another 0.5 h. The vacuum degree was then reduced to below 80 Pa and the reaction was continued for another 1.5 h to obtain a white PGA crystalline polymer with a number average molecular weight of 45900 Da. The PGA crystalline polymer obtained by melting was cut into granules and dried under vacuum at 100-120℃ to remove water, thus obtaining PGA granules. The PGA granules were then fed into a vacuum drum reactor for solid-phase polycondensation at a temperature of 195℃ for 20 h, resulting in white PGA solid material. The amount of glycolide and oligomers collected was 670 g.

[0032] Phase Two: ICP analysis of the collected PGA oligomers and glycolide during the polymerization process showed a tin content of 0%, indicating no catalyst residue in the glycolide and oligomers. 670 grams of the collected PGA oligomers and glycolide were mixed with 1700 grams of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated. A white PGA solid was obtained. In this step, the amounts of antioxidants and stabilizers were calculated based on the total mass of the PGA oligomers, glycolide, and glycolic acid.

[0033] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times.

[0034] Example 6 First stage: 100 mol glycolic acid and 5 mmol stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then increased to 3000 Pa and the reaction was continued for 1 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added to the system. The system temperature was increased to 220 °C and the reaction was carried out at 1250 Pa for 2 h. The vacuum degree was controlled at 750 Pa and the reaction was continued for 2 h. The vacuum degree was reduced to below 70 Pa and the reaction was continued for 2 h to obtain a white PGA crystalline polymer with a number average molecular weight of 48500 Da. The PGA crystalline polymer obtained by melting was cut into granules and dried under vacuum at 100-120℃ to remove water, thus obtaining PGA granules. The PGA granules were then fed into a vacuum drum reactor for solid-phase polycondensation at a temperature of 195℃ for 20 h, resulting in white PGA solid material. The amount of glycolide and oligomers collected was 690 g.

[0035] Phase Two: ICP analysis of the collected PGA oligomers and glycolide during the polymerization process showed a tin content of 0%, indicating no catalyst residue in the glycolide and oligomers. 690 grams of the collected PGA oligomers and glycolide were mixed with 1700 grams of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated. A white PGA solid was obtained. In this step, the amounts of antioxidants and stabilizers were calculated based on the total mass of the PGA oligomers, glycolide, and glycolic acid.

[0036] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times.

[0037] Example 7 The preparation method is the same as in Example 1, except that in the second stage, 1 / 1000 by weight of glycolic acid stannous octoate is added.

[0038] Example 8 The preparation method is the same as in Example 1, except that the catalyst is replaced with 5 mmol titanium tetrachloride, the antioxidant is replaced with 80 ppm α-tocopherol and 75 ppm 5-tert-butyl-4-hydroxy-2-methylphenyl sulfide (Antioxidant 300), and the stabilizer is replaced with 75 ppm triethyl phosphate (TEP).

[0039] Example 9 The preparation method is the same as in Example 1, except that the catalyst is replaced with 2 mmol titanium dioxide and 4 mmol stannous chloride, the antioxidant is replaced with 90 ppm TH-330, and the stabilizer is replaced with 100 ppm IRGANOX 3052.

[0040] Example 10 The preparation method is the same as in Example 1, except that glycolic acid is replaced with methyl glycolate.

[0041] Comparative Example 1 First stage: 100 mol glycolic acid and 5 mmol stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then increased to 3000 Pa and the reaction was continued for 1 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added to the system. The system temperature was increased to 220 °C and the reaction was carried out at 3000 Pa for 1 h. The vacuum degree was controlled at 1500 Pa and the reaction was continued for 1 h. The vacuum degree was reduced to below 200 Pa and the reaction was continued for 3 h to obtain yellow PGA with a number average molecular weight of 43000 Da. PGA granules were fed into a vacuum drum reactor for solid-state polycondensation at 195°C for 20 h, yielding a white PGA solid with a yield of 65%. The polymer's B value was 3.9, number-average molecular weight was 70,000 Da, weight-average molecular weight was 86,100, and molecular weight distribution was 1.95. 1700 g of glycolide and oligomers were collected.

[0042] Second stage: The PGA oligomers and glycolide collected during the polymerization process were analyzed by ICP and found to contain 16 ppm of tin. 1700 g of the collected PGA oligomers and glycolide were mixed with 4250 g of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated. A deep yellow PGA solid was obtained with a yield of 65%. The polymer's B value was 7.0, number-average molecular weight was 63700 Da, weight-average molecular weight was 90500, and molecular weight distribution was 1.99.

[0043] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times, with a total PGA yield of 73%.

[0044] Comparative Example 2 First stage: 100 mol glycolic acid and 5 mmol stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then increased to 3000 Pa and the reaction was continued for 1 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added to the system. The system temperature was increased to 220 °C and the reaction was carried out at 3000 Pa for 1 h. The vacuum degree was controlled at 500 Pa and the reaction was continued for 1 h. The vacuum degree was reduced to below 70 Pa and the reaction was continued for 2 h to obtain light yellow PGA with a number average molecular weight of 45000 Da. PGA granules were fed into a vacuum drum reactor for solid-phase polycondensation at 195°C for 20 h, yielding a light yellow PGA solid with a yield of 69%. The polymer's B value was 3.2, number-average molecular weight was 71,000 Da, weight-average molecular weight was 83,100, and molecular weight distribution was 1.85. 1300 g of glycolide and oligomers were collected.

[0045] Second stage: The PGA oligomers and glycolide collected during the polymerization process were analyzed by ICP and found to contain 14 ppm of tin. 1300 g of the collected PGA oligomers and glycolide were mixed with 3250 g of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated. A yellow PGA solid was obtained with a yield of 69%. The polymer's B value was 6.6, number-average molecular weight was 60,500 Da, weight-average molecular weight was 90,000, and molecular weight distribution was 2.01.

[0046] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times, with a total PGA yield of 76%.

[0047] Comparative Example 3 First stage: 100 mol glycolic acid and 5 mmol stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then increased to 3000 Pa and the reaction was continued for 1 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added to the system. The system temperature was increased to 220 °C and the reaction was carried out at 1000 Pa for 1 h. The vacuum degree was controlled at 1500 Pa and the reaction was continued for 1 h. The vacuum degree was reduced to below 70 Pa and the reaction was continued for 2 h to obtain light yellow PGA with a number average molecular weight of 48000 Da. PGA granules were fed into a vacuum drum reactor for solid-phase polycondensation at 195°C for 20 h, yielding a light yellow PGA solid with a yield of 70%. The polymer's B value was 3.2, number-average molecular weight was 73,000 Da, weight-average molecular weight was 87,000, and molecular weight distribution was 1.79. 1400 g of glycolide and oligomers were collected.

[0048] Second stage: The PGA oligomers and glycolide collected during the polymerization process were analyzed by ICP and found to contain 15 ppm of tin. 1400 g of the collected PGA oligomers and glycolide were mixed with 3500 g of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated. A yellow PGA solid was obtained with a yield of 70%. The polymer's B value was 6.5, number-average molecular weight was 58,500 Da, weight-average molecular weight was 89,000, and molecular weight distribution was 1.91.

[0049] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times, with an overall PGA yield of 77%.

[0050] Comparative Example 4 First stage: 100 mol of glycolic acid and 5 mmol of stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then increased to 3000 Pa and the reaction was continued for 1 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added to the system. The system temperature was increased to 220 °C and the reaction was carried out at 1000 Pa for 1 h. The vacuum degree was controlled at 500 Pa and the reaction was continued for 1 h. The vacuum degree was reduced to below 200 Pa and the reaction was continued for 2.5 h to obtain yellow PGA with a number average molecular weight of 48000 Da. PGA granules were fed into a vacuum drum reactor for solid-phase polycondensation at 195°C for 20 h, yielding a yellow PGA solid with a yield of 67%. The polymer's B value was 5.2, number-average molecular weight was 73,000 Da, weight-average molecular weight was 87,000, and molecular weight distribution was 1.83. 1600 g of glycolide and oligomers were collected.

[0051] Second stage: The PGA oligomers and glycolide collected during the polymerization process were analyzed by ICP and found to contain 17 ppm of tin. 1600 g of the collected PGA oligomers and glycolide were mixed with 4000 g of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated. A deep yellow PGA solid was obtained with a yield of 67%. The polymer's B value was 7.1, number-average molecular weight was 58,500 Da, weight-average molecular weight was 89,000, and molecular weight distribution was 1.97.

[0052] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times, with a total PGA yield of 75%.

[0053] Comparative Example 5 First stage: 100 mol glycolic acid and 5 mmol stannous octoate were added to a 10 L polymerization reactor. The temperature was raised to 190 °C and the reaction was carried out at atmospheric pressure for 0.5 h. The system pressure was then changed to 3000 Pa and the reaction was continued for 1 h to obtain PGA oligomers with a number average molecular weight of 5000-10000 Da. Antioxidant 1010 (70 ppm), THP-24 (75 ppm), and Revonox 420 (65 ppm, relative to the mass of glycolic acid) were added. The system temperature was raised to 220 °C and the vacuum degree was controlled at 65 Pa. Polycondensation was carried out for 4 h. The material was cooled and granulated under vacuum to obtain white PGA with a number average molecular weight of 46000 Da. A total of 2000 g of glycolide and PGA oligomers were collected during the polycondensation process. PGA granules were fed into a vacuum drum reactor for solid-phase polycondensation at a temperature of 198°C for 20 h, yielding a white PGA solid with a yield of 61%. The polymer B value was 2.2, the number average molecular weight was 60,000 Da, the weight average molecular weight was 87,600, and the molecular weight distribution was 1.46.

[0054] Second stage: The PGA oligomers and glycolide collected during the polymerization process were analyzed by ICP and found to contain 22 ppm of tin. 2000 g of the collected PGA oligomers and glycolide were mixed with 5000 g of glycolic acid, and 1 / 10,000 (by weight) stannous octoate was added. The above experiment was repeated. A deep yellow PGA solid was obtained with a yield of 61%. The polymer's B value was 7.3, number-average molecular weight was 68500 Da, weight-average molecular weight was 89500, and molecular weight distribution was 1.57.

[0055] Phase 3: Repeat the above experimental procedures to achieve a semi-continuous preparation of PGA. Repeat the cycle 5 times, with an overall PGA yield of 70%.

[0056] The products prepared from the examples and comparative examples were evaluated in the following tests, and the results are shown in Table 1.

[0057] A. Weight-average molecular weight and its distribution The sample was dissolved in a 5 mmol / L sodium trifluoroacetate solution in hexafluoroisopropanol to prepare a 0.05–0.3 wt% solution. This solution was filtered through a 0.4 μm PTFE filter. 20 μL of the filtered solution was added to a gel permeation chromatography (GPC) injector to determine the molecular weight of the sample. Five standard molecular weights of methyl methacrylate with different molecular weights were used for molecular weight correction.

[0058] B. Colorimetric test The PGA pellets were placed in a vacuum oven at 40°C and dried for 5 hours. After cooling to room temperature, they were removed and placed in a sample cup to ensure compact packing. The sample was then placed in the measuring hole of an automatic colorimeter to measure its color. The results are expressed as HunterLab color system L, a, b.

[0059] C. Tin content test in byproducts glycolide and oligomers Take 0.5g of byproduct glycolide and oligomer sample and dissolve it in 2mL of 2% HNO3 solution. Use inductively coupled plasma mass spectrometry (ICP) to test the tin content in the sample.

[0060] D. Yield calculation Yield / % = Actual product mass / Theoretical product mass × 100% Table 1 Test Results

[0061]

[0062] As can be seen from Examples 1-10, within the key preparation process range described in this invention (i.e., the system temperature is raised to 200-230℃, and the vacuum degree is controlled at 1500-1000 Pa for 0.5-2 h; the vacuum degree is controlled at 1000-500 Pa, and the reaction continues for 0.5-2 h; the vacuum degree is reduced to below 90 Pa, and the reaction continues for 0.5-2 h), the release of by-products glycolide and oligomers can be effectively reduced during the polymerization process, thereby increasing the product yield. Furthermore, the recovered by-product glycolide, as determined by ICP analysis, has a metal element content of 0, indicating that there is no catalyst residue in the glycolide and oligomers. It can be directly reused in the reaction system, further improving the product yield without affecting product quality, and realizing the continuous production of PGA by recycling by-products. As can be seen from Comparative Examples 1-5, outside the scope of the key preparation process described in this invention, the release of by-products glycolide and oligomers during polymerization increases significantly, the product yield decreases, and catalyst residues are present in the recovered by-products glycolide and oligomers. Direct reuse in the reaction system can improve the product yield, but the product quality and stability are affected, and the requirements for continuous production cannot be met.

Claims

1. A method for preparing polyglycolic acid by direct esterification, comprising the following steps: (1) Glycolic acid or methyl glycolate is mixed with a catalyst and reacted to obtain polyglycolic acid oligomers; (2) Mix the polyglycolic acid oligomer with antioxidants and stabilizers, raise the system temperature to 200-230℃, and react at a vacuum of 1500-1000 Pa for 0.5-2 h; then, control the vacuum at 1000-500 Pa and continue the reaction for 0.5-2 h; finally, reduce the vacuum to below 90 Pa and continue the reaction for 0.5-2 h to obtain a polyglycolic acid crystalline polymer. (3) The polyglycolic acid crystalline polymer is subjected to solid-phase polycondensation reaction to obtain the polyglycolic acid.

2. The method according to claim 1, characterized in that: The catalyst is one or more of titanium tetrachloride, stannous octoate, stannous chloride, tetrabutyl titanate, and titanium dioxide. The molar ratio of glycolic acid or methyl glycolate to the catalyst is 13-25 mol: 1 mmol; The antioxidant is one or more of pentaerythritol tetra(bis-tert-butylhydroxyhydrogenated cinnamic acid) ester (Antioxidant 1010), α-tocopherol, 5-tert-butyl-4-hydroxy-2-methylphenyl sulfide (Antioxidant 300), and 2-tert-butyl-6-(3-tert-butyl-2-hydroxy-5-methylphenyl)methyl-4-methylphenyl acrylate (TH-330); The antioxidant is 50-250 ppm of the mass of glycolic acid or methyl glycolate; The stabilizing agent is one or more of the following: bis(2,4-di-tert-butylphenyl)pentaerythritol diphosphite (THP-24), diphenyl phosphite, triphenyl phosphite (TPP), triethyl phosphate (TEP), tris(2,4-di-tert-butylphenyl) phosphite (Antioxidant 168), N,N-bis(n-octadecane)hydroxylamine (Revonox 420), and 2-(2-hydroxy-3-tert-butyl-5-methylbenzyl)-4-methyl-6-tert-butylphenyl acrylate (IRGANOX 3052); The mass of the stabilizing agent is 60-230 ppm of the mass of the glycolic acid or methyl glycolate.

3. The method according to claim 1 or 2, characterized in that: In step (1), glycolic acid or methyl glycolate is mixed with the catalyst, heated to 170-220℃ and reacted at atmospheric pressure for 0.5-2 h until no more distillate is distilled out. The system is then changed to a rough vacuum of 3000-2000 Pa and the reaction continues for another 0.5-2 h until the theoretical water yield of the system reaches more than 98%, thus obtaining the polyglycolic acid oligomer. In step (3), the temperature of the solid-phase polycondensation reaction is 195-210℃; the time of the solid-phase polycondensation reaction is 10-35h.

4. The method according to any one of claims 1-3, characterized in that: Step (3) also includes cutting the polyglycolic acid crystal polymer into granules, drying and removing water; and then carrying out a solid-phase polycondensation reaction.

5. A semi-continuous preparation method for polyglycolic acid, comprising the following steps: S1. Glycolic acid or methyl glycolate is mixed with a catalyst and reacted to obtain polyglycolic acid oligomers. S2. Mix the polyglycolic acid oligomer with antioxidants and stabilizers, raise the system temperature to 200-230℃, and react under a vacuum of 1500-1000 Pa for 0.5-2 h; then, control the vacuum at 1000-500 Pa and continue the reaction for 0.5-2 h; finally, reduce the vacuum to below 90 Pa and continue the reaction for 0.5-2 h to obtain a crystalline polyglycolic acid polymer; and collect the byproducts, polyglycolic acid oligomer and glycolide, during this process. S3. The polyglycolic acid crystalline polymer is subjected to a solid-state polycondensation reaction to obtain the polyglycolic acid; S4. The by-product polyglycolic acid oligomer collected in step S2 is mixed with glycolide and glycolic acid or methyl glycolate as the starting material for the reaction, and steps S1-S3 are repeated. S5. Repeat step S4 multiple times.

6. The semi-continuous preparation method according to claim 5, characterized in that: In step S1, the catalyst is one or more of titanium tetrachloride, stannous octoate, stannous chloride, tetrabutyl titanate, and titanium dioxide. The molar ratio of glycolic acid or methyl glycolate to the catalyst is 13-25 mol: 1 mmol; In step S2, the antioxidant is one or more of pentaerythritol tetra(bis-tert-butylhydroxyhydrocinnamic acid) ester (Antioxidant 1010), α-tocopherol, 5-tert-butyl-4-hydroxy-2-methylphenyl sulfide (Antioxidant 300), and 2-tert-butyl-6-(3-tert-butyl-2-hydroxy-5-methylphenyl)methyl-4-methylphenyl acrylate (TH-330); The antioxidant is 50-250 ppm of the mass of glycolic acid or methyl glycolate; The stabilizing agent is one or more of the following: bis(2,4-di-tert-butylphenyl)pentaerythritol diphosphite (THP-24), diphenyl phosphite, triphenyl phosphite (TPP), triethyl phosphate (TEP), tris(2,4-di-tert-butylphenyl) phosphite (Antioxidant 168), N,N-bis(n-octadecane)hydroxylamine (Revonox 420), and 2-(2-hydroxy-3-tert-butyl-5-methylbenzyl)-4-methyl-6-tert-butylphenyl acrylate (IRGANOX 3052); The mass of the stabilizing agent is 60-230 ppm of the mass of the glycolic acid or methyl glycolate.

7. The semi-continuous preparation method according to claim 5 or 6, characterized in that: In step S1, glycolic acid or methyl glycolate is mixed with a catalyst and heated to 170-220°C under normal pressure for 0.5-2 h until no more distillate is distilled off. The system is then subjected to a rough vacuum of 3000-2000 Pa and the reaction continues for another 0.5-2 h until the theoretical water yield reaches over 98%, thus obtaining the polyglycolic acid oligomer. In step S3, the temperature of the solid-phase polycondensation reaction is 195-210℃; the time of the solid-phase polycondensation reaction is 10-35h.

8. The semi-continuous preparation method according to any one of claims 5-7, characterized in that: Step S3 also includes cutting the polyglycolic acid crystal polymer into granules, drying and removing water; and then carrying out a solid-phase polycondensation reaction.

9. The semi-continuous preparation method according to any one of claims 5-8, characterized in that: In step S4, the mass of the catalyst is one ten-thousandth to one thousandth of the mass of the glycolic acid; The antioxidant is 50-250 ppm of the total mass of the byproduct polyglycolic acid oligomer, glycolide, and glycolic acid or methyl glycolate. The mass of the stabilizing agent is 60-230 ppm of the total mass of the byproduct polyglycolic acid oligomer, glycolide, and glycolic acid or methyl glycolate.

10. The semi-continuous preparation method according to any one of claims 5-9, characterized in that: In step S5, step S4 is repeated 2-10 times.

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