Purification method of glycolide, glycolide obtained by purification method and application of glycolide

Abstract

The invention provides a glycolide purification method, glycolide obtained through the glycolide purification method and application of the glycolide. The purification method comprises the following steps: fully and uniformly mixing a solid-liquid mixture, settling particles in the solid-liquid mixture, removing the particles with slow settling rate, and recovering the remaining solid-phase particles to obtain purified glycolide; the solid-liquid mixture comprises a glycolide solid phase and a glycolide saturated solution; optionally, the recovered solid phase is dried. The purification method provided by the invention can quickly and efficiently remove oligomer impurities in glycolide, has the advantages of low oligomer impurity content and high glycolide purity after glycolide purification, is simple to operate, and has great industrial application value.

Description

Technical Field

[0001] The present invention relates to the technical field of glycolide, and further relates to a method for purifying glycolide, the obtained glycolide and its application. Background Art

[0002] Polyglycolic acid (PGA) is a biodegradable polymer with good biocompatibility and biodegradability. Polyglycolic acid is formed by ring-opening polymerization of cyclic ester monomer glycolide under the action of a catalyst, and can be prepared into materials of different shapes, such as fibers, membranes, microspheres, sponges, etc.

[0003] Polyglycolic acid absorbable sutures are widely used in surgical operations due to their good biocompatibility, good degradation performance, and no foreign body reaction. The absorption rate of polyglycolic acid sutures is moderate, neither too fast nor too slow, and different absorption rates and suture diameters can be selected according to the surgical site and suture needs. Polyglycolic acid is also used as a manufacturing material for medical devices such as medical syringes, medical straws, and oral sutures; in addition, polyglycolic acid is also applied in the fields of tissue engineering, drug delivery, biosensors, etc.

[0004] PGA used for medical sutures, stents, dressings, and fracturing balls needs to use polymerization-grade glycolide for polymerization. Glycolide needs to have high purity and low terminal carboxyl group content to meet the requirements for preparing spinning-grade or injection-molding-grade PGA after polymerization. Usually, the terminal carboxyl group content should be at least less than 10 μmol / g.

[0005] Currently, the most mature synthesis method of glycolide at home and abroad is the polycondensation-depolymerization method using glycolic acid as the raw material. The crude glycolide obtained from the depolymerization reaction usually contains various impurities such as water and glycolic acid. Usually, a purification means is reused or a combination of multiple purification means is used to fully remove the above various impurities.

[0006] There are many schemes for purifying glycolide using organic solvents in the prior art, and most of them produce a solid-liquid mixture of glycolide and organic solvent during the purification process. For example, Peng Song et al. proposed a process for purifying glycolide by alcohol washing in a 2015 paper (Peng Song, Cui Aijun, Yin Fanghua, et al. Process for purifying glycolide by alcohol washing and its influence on ring-opening polymerization reaction [J]. Chemical Industry Progress, 2015, 34(04): 1059-1063.), and studied its influence on ring-opening polymerization reaction. In this method, a large amount of alcohol is mixed with crude glycolide particles to form a solid-liquid mixture, and the impurities on the surface and inside of the particles diffuse and dissolve into the alcohol, and then the glycolide particles are recovered by solid-liquid separation. This process is repeated several times to gradually reduce the impurity level in glycolide. In addition, Chinese invention patent CN107868075A discloses a method for purifying crude glycolide, which uses a combination of cooling recrystallization and poor solvent mixed washing for purification. After cooling and recrystallization or poor solvent mixed washing, a solid-liquid mixture of glycolide particles and organic solvent will be produced, in which the solid phase is recovered by solid-liquid separation, and the impurities are taken away by the organic solvent.

[0007] It is relatively easy to remove small molecular impurities in glycolide, because at room temperature, small molecular impurities, which are mainly polar molecules, have high solubility in organic solvents commonly used in the art. Chinese invention patent CN107868074A discloses a technical solution for purifying glycolide by evaporation crystallization-extraction combination, which claims that "high molecular weight impurities in glycolide are usually glycolic acid oligomers with a degree of polymerization greater than or equal to 4"; the technical solution aims to remove high molecular weight impurities, and the main method is to perform a one-step filtration before evaporation crystallization to remove insoluble impurities in the crystallization solution.

[0008] The existing technology usually only performs solid-liquid separation on the solid-liquid mixture of glycolide and organic solvent. It is still necessary to study the physical properties such as the particle size distribution of the particles in the solid-liquid mixture and develop more processing methods to further improve the purity of the recovered solid phase. Summary of the invention

[0009] In order to solve the technical problems existing in the prior art, the present invention provides a method for purifying glycolide and the glycolide obtained and its application.

[0010] The glycolide purification method provided by the present invention comprises a particle sedimentation process after glycolide and an organic solvent solid-liquid mixture are fully mixed, particles with a slow sedimentation rate are removed from the solid phase and the remaining solid phase is collected, and the obtained solid phase has the characteristics of low impurity content of glycolic acid oligomers. The present invention provides a novel method for removing oligomer impurities from polymerized monomers, which is simple to operate and has great industrial application value.

[0011] In the prior art, during the solid-liquid separation operation of the glycolide-organic solvent solid-liquid mixture, oligomer impurities are mixed into the recovered solid phase, thereby reducing the purification effect of glycolide. In the present invention, after the solid-liquid mixtures formed by processes such as recrystallization and solvent washing are fully mixed, the glycolide particles therein are allowed to settle. After removing the particles with slow settling rate, the solid phase is recovered by solid-liquid separation, which can quickly and efficiently remove the oligomer impurities in glycolide, and has the advantages of low content of oligomer impurities and high purity of glycolide after purification.

[0012] Through experimental analysis, the present invention has a new understanding of the composition of glycolide particles, that is, glycolide particles are composed of particles with different settling rates, and the slower the settling rate of the particles, the more oligomer impurities and the lower the purity. Therefore, by utilizing the difference in the settling rates of glycolide particles, during the solid-liquid separation operation of the glycolide-solvent mixture, the glycolide particles are selectively collected, and the particles with slower settling rates are removed, thereby improving the purity of glycolide.

[0013] One of the objectives of the present invention is to provide a method for purifying glycolide, comprising the following steps:

[0014] (1) Fully mix the solid-liquid mixture evenly and allow the particles therein to settle, remove the particles with slow settling rate, and recover the remaining solid-phase particles to obtain purified glycolide; the solid-liquid mixture comprises a glycolide solid phase and a glycolide saturated solution;

[0015] Optionally, (2) dry the solid phase recovered in step (1).

[0016] In a preferred embodiment of the present invention,

[0017] The proportion of the particles with slow settling rate in the total weight of all solid phases in the solid-liquid mixture is less than or equal to 10% by weight, preferably 1-10% by weight;

[0018] According to Stokes' law under gravity conditions or Stokes' law under centrifugal conditions, the settling rate is proportional to the square of the equivalent particle diameter; under gravity conditions, the magnitude of the settling rate is affected not only by the particle diameter but also by the density and viscosity of the dispersant (solvent); under centrifugal conditions, the magnitude of the settling rate is affected not only by the particle diameter but also by the density and viscosity of the dispersant (solvent), the angular velocity of the centrifuge (the rotation speed of the centrifuge), and the distance from the particle to the centrifuge axis (the size of the centrifuge equipment). Therefore, the settling speed is a relative value, and thus the present invention defines the particles with slow settling rate by the particle weight proportion.

[0019] The median diameter of the particles with slow settling rate is less than or equal to 90 microns, preferably less than or equal to 60 microns;

[0020] The content of oligomer impurities in the particles with a slow sedimentation rate is greater than or equal to 1% by weight, preferably greater than or equal to 2.5% by weight, and more preferably greater than or equal to 4% by weight.

[0021] The inventors found through experiments that when the content of oligomer impurities in the particles exceeds 2.5%, the sedimentation rate of the particles is significantly reduced. However, when the impurity content is between 1% and 2.5%, there is still an impact on the sedimentation rate. From the perspective of separation, only the sedimentation distance needs to be extended, and this part of the particles can still be separated from the main particles.

[0022] In a preferred embodiment of the present invention,

[0023] Step (1),

[0024] The solid-liquid mixture is obtained by adding molten crude glycolide to an organic solvent in at least one of the ways of dropping, injecting, spraying, showering, and atomizing; preferably,

[0025] The molten crude glycolide is unpurified molten crude glycolide and / or purified molten crude glycolide; and / or,

[0026] The mass content of glycolide in the molten crude glycolide is 85% - 99%.

[0027] The gaseous crude glycolide generated by the depolymerization reaction becomes liquid after heat exchange and condensation, stays for a period of time or is immediately added to the organic solvent in at least one of the ways of dropping, injecting, spraying, showering, and atomizing. The liquid crude glycolide quickly solidifies into solid-phase particles when it meets cold, and forms a solid-liquid mixture with the organic solvent; the purified solid-phase glycolide can also form a molten state after being heated and melted, or the liquid glycolide generated by processes such as melt crystallization is added to the organic solvent in at least one of the above ways, and a solid-liquid mixture can also be generated.

[0028] For example, the molten crude glycolide can be obtained by the following method:

[0029] After adding glycolic acid (crystal or aqueous solution) and stannous octoate catalyst to the reactor, after complete dissolution, the temperature is raised for atmospheric pre-polymerization. After pre-polymerization, the temperature is further raised for polymerization, the system maintains the temperature and starts to evacuate. After no water vapor is distilled out, glycolic acid oligomer is obtained; the obtained glycolic acid oligomer is subjected to a depolymerization reaction in a depolymerization reactor to obtain crude glycolide, and the crude glycolide vapor produced by the depolymerization reactor is condensed at a higher temperature (such as 80 - 90 °C) to obtain molten crude glycolide.

[0030] In a preferred embodiment of the present invention,

[0031] Step (1),

[0032] The solid-liquid mixture is obtained by adding solid-phase crude glycolide to an organic solvent; preferably,

[0033] The solid crude glycolide is preferably obtained by condensing and solidifying the molten crude glycolide.

[0034] The gaseous crude glycolide generated by the depolymerization reaction becomes solid after heat exchange and condensation, and after being processed by means of controlling the particle size such as crushing and pulverizing, it is added to an organic solvent and mixed with the organic solvent to form a solid-liquid mixture.

[0035] For example: in the method for obtaining the molten crude glycolide described above, after obtaining the crude glycolide, the crude glycolide vapor produced by the depolymerization reactor is condensed at a lower temperature (such as 0-10°C) to obtain the solid crude glycolide.

[0036] In a preferred embodiment of the present invention,

[0037] Step (1),

[0038] The solid-liquid mixture is obtained by mixing the glycolide solid phase with an organic solvent; preferably, the glycolide solid phase is a wet filter cake or purified glycolide after drying treatment.

[0039] The glycolide solid phase recovered after the solid-liquid separation operation of any glycolide-organic solvent solid-liquid mixture generated in the previous process can form a solid-liquid mixture by adding an organic solvent. The previous process includes but is not limited to washing, extraction, and crystallization, and a certain amount of the organic solvent from the previous process usually remains in the solid phase recovered after the solid-liquid separation operation. When the glycolide solid phase is a wet filter cake, the moisture content of the wet filter cake obtained by the conventional solid-liquid separation operation is generally less than or equal to 30%, and the mass fraction of the organic solvent in the glycolide solid phase is not less than 30% by weight; when the glycolide solid phase is purified glycolide after drying treatment, a certain amount of the organic solvent usually remains in the purified glycolide product after drying treatment, and the mass fraction of the organic solvent in the glycolide solid phase is greater than or equal to 30 ppm.

[0040] In a preferred embodiment of the present invention,

[0041] Step (1),

[0042] The solid-liquid mixture is obtained by cooling crystallization or evaporation crystallization of a glycolide solution; preferably, the glycolide solution is a solution formed by dissolving molten or solid crude glycolide in an organic solvent.

[0043] A saturated or unsaturated glycolide solution is formed by dissolving molten or solid crude glycolide in an organic solvent. The solution is filtered to remove insoluble substances with any filtration accuracy, and then the solution is crystallized by at least one of the methods of cooling, evaporation, and adding an antisolvent, and the precipitated particles and the solution are combined to form a solid-liquid mixture.

[0044] The above lists 4 sources of the solid-liquid mixture, and the solid-liquid mixture of the present invention includes but is not limited to the above 4 sources.

[0045] In a preferred embodiment of the present invention,

[0046] The organic solvent is at least one of acetone, ethyl acetate, ethylene glycol dimethyl ether, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, n-pentanol, isopentanol, n-hexane, cyclohexane, pentane, petroleum ether.

[0047] In a preferred embodiment of the present invention,

[0048] Step (1),

[0049] The mass fraction of the solid phase in the solid-liquid mixture is less than or equal to 50%, preferably less than or equal to 40%, more preferably 5-40%, and most preferably 20-40%; the purpose of the mass fraction of the solid phase being less than or equal to 50% is to increase the average distance between particles in the mixture, so that the solid-liquid mixture can be easily mixed, slurried and made uniform under the action of methods such as stirring, oscillation, gas fluidization, rotating barrel, etc.

[0050] The median diameter of the solid phase in the solid-liquid mixture is less than or equal to 600 microns, preferably less than or equal to 500 microns;

[0051] First, the purpose of the median diameter of the solid phase being less than or equal to 600 microns is to increase the average sedimentation time of the particles, so that the particles in the solid-liquid mixture can be more easily distinguished into particles with different sedimentation rates and occupy different positions in the flow field when settling under the influence of gravity, centrifugal force or convection, which is beneficial to separating the particles with slow sedimentation rate and part of the solution from the solid-liquid mixture.

[0052] Secondly, when the particle size of the solid phase is within 600 microns, the solid-liquid mixture is easily mixed and uniform. If the particle size is too large, it is difficult to make the solid-liquid mixture uniform by conventional dispersion means (such as stirring), and there is also a phenomenon of particle adhesion and agglomeration. The particles to be separated are agglomerated with the normal particles, which will cause separation difficulties; if unconventional dispersion means such as homogenization or high-speed shearing are used, the solid-liquid mixture with a solid phase particle size exceeding 600 microns can also be mixed and uniform, but these unconventional dispersion means have a strong mechanical force on the particles, which can cause the particles to break and the particle size to become smaller, still falling within the particle size range.

[0053] The liquid phase of the solid-liquid mixture is a saturated solution of glycolide in an organic solvent;

[0054] The mixing of the solid-liquid mixture can be carried out by methods commonly used in the prior art, such as stirring, oscillation, gas fluidization, rotating barrel, etc. to achieve uniformity; the uniformity means that the density deviation between any parts of the solid-liquid mixture does not exceed 30%, preferably not exceed 20%.

[0055] Taking the sedimentation of particles under the action of gravity as an example, the uniformly mixed solid-liquid mixture is allowed to stand still. The particles with a fast sedimentation rate move to the bottom of the container in a shorter time, while the particles with a slow sedimentation rate remain suspended in the solvent for a longer time and slowly move to the bottom of the container. After standing still for a certain period of time, the suspension near the liquid surface is separated from the solid-liquid mixture by means such as overflow, and the solid phase with a slow sedimentation rate in the suspension can be taken away together.

[0056] In a preferred embodiment of the present invention,

[0057] Step (1),

[0058] The way of particle sedimentation is that the particles sediment under at least one of gravity, centrifugal force, and convection;

[0059] The way of removing the particles with a slow sedimentation rate is to separate the part of the solution containing the particles with a slow sedimentation rate from the solid-liquid mixture or to separate the particles with a slow sedimentation rate from the solid phase after separating from the solid-liquid mixture;

[0060] For example, the particles with a slow sedimentation rate can be removed by one of the following methods:

[0061] Method 1: The solid-liquid mixture can be sedimented by gravity in a container, record the liquid level H1 of the solid-liquid mixture in the container. There is a stirring device in the container and a device for controlling the liquid temperature in the container, such as a jacket, etc. At a set temperature (such as 0-60 °C), stir the solid-liquid mixture at a certain rate (such as 100-1000 rpm) for a certain time (such as 1-10 min), then stop stirring. After sedimenting for a certain time (such as 15-180 seconds), use a hose inserted to the depth of liquid level H2 and a pneumatic diaphragm pump to pump out the upper suspension from the container in a short time (such as 5-20 seconds). The particles in the taken-out solid-liquid mixture are used as the particles with a slow sedimentation rate, where H2 / H1 can be 1 / 5-4 / 5. Determine the value of H2 / H1 according to the ratio of the solid-phase particles in the taken-out upper suspension to the total solid weight, the median diameter of the solid-phase particles in the taken-out upper suspension, and the content of oligomer impurities in the solid-phase particles in the taken-out upper suspension.

[0062] Method 2: Under a certain stirring speed (such as 100-1000 rpm), the solid-liquid mixture is fed into the bottom inlet of a tubular centrifuge (such as a tubular centrifuge with a rotation speed of 3000 rpm and an inner cylinder diameter of 100 mm) through a centrifugal pump. The suspension is obtained from the top clear liquid outlet of the centrifuge and used as the particles with a slow sedimentation rate.

[0063] Method 3: The solid-liquid mixture can be subjected to gravitational sedimentation in a container with a filtration medium (such as filter cloth, filter screen) at the bottom. A stirring device is provided in the container, and a device for controlling the liquid temperature in the container, such as a jacket, etc., is provided. At a set temperature (such as 0 - 60 °C), the solid-liquid mixture is stirred at a certain rate (such as 100 - 1000 rpm) for a certain time (such as 1 - 10 min) to make it uniform, and then the stirring is stopped. After the particles are allowed to settle sufficiently for a certain time (such as 180 - 1800 seconds), an inert gas (such as nitrogen) is introduced into the container for solid-liquid separation. The filtrate is discharged from the container through the filtration medium to obtain a wet filter cake. The height of the wet filter cake in the container is recorded as H1, and the wet filter cake layer above the height H2 is taken out of the container with a scraper. The particles in the taken-out wet filter cake are used as the particles with a slow sedimentation rate, where H2 / H1 can be 0.90 - 0.99. The value of H2 / H1 is determined according to the ratio of the solid-phase particles in the taken-out upper wet filter cake to the total solid weight, the median diameter of the solid-phase particles in the taken-out upper wet filter cake, and the content of oligomer impurities in the solid-phase particles in the taken-out upper wet filter cake.

[0064] The method for recovering the remaining solid-phase particles is centrifugation or filtration;

[0065] After sedimentation and separation to remove the upper suspension, the remaining solid-liquid mixture is suction-filtered, and the wet filter cake is obtained after collection; further purification and drying are carried out to obtain refined glycolide.

[0066] In the step (2), the solid-phase drying method is convective drying under a thermal inert gas or heat conduction drying under vacuum.

[0067] Both the drying temperature and the drying time adopt the usual conditions in the art, for example, but not limited to vacuum drying at 40 - 80 °C for 2 - 10 hours.

[0068] In a preferred embodiment of the present invention,

[0069] Steps (1) and optionally step (2) are repeated at least once.

[0070] The second object of the present invention is to provide a glycolide obtained by the above purification method.

[0071] The third object of the present invention is to provide an application of the glycolide obtained by the above purification method in the preparation of polyglycolic acid.

[0072] Compared with the prior art, the beneficial effects of the present invention:

[0073] In the prior art, the solid-liquid separation treatment is usually only carried out on the solid-liquid mixture of glycolide and organic solvent. The present invention provides a new method for removing oligomer impurities from the solid-liquid mixture containing glycolide. After the solid-liquid mixture containing glycolide and organic solvent is fully mixed, particle sedimentation is carried out, and the particles with slow sedimentation rate are removed from the solid phase, and then the remaining solid phase is collected. The obtained solid phase has a low content of glycolic acid oligomer impurities, simple operation, and great industrial application value.

[0074] The present invention can process the solid-liquid mixture containing glycolide obtained from various sources in the prior art. The treatment method is simple, and can quickly and efficiently remove the oligomer impurities in glycolide, having the advantages of low content of oligomer impurities and high purity of glycolide after purification of glycolide. Specific embodiments

[0075] The present invention will be specifically described below in conjunction with specific embodiments. It is necessary to point out here that the following embodiments are only used for further illustration of the present invention, and cannot be understood as limiting the protection scope of the present invention. Some non-essential improvements and adjustments made by those skilled in the art according to the content of the present invention still fall within the protection scope of the present invention.

[0076] The raw materials used in the embodiments are all conventional commercially available raw materials.

[0077] The method for testing the average particle size of glycolide crystals in the present invention is as follows:

[0078] Use the Mastersizer 3000 laser particle size analyzer of Malvern Company to measure the average particle size (median diameter, that is, the particle size with a particle cumulative volume distribution of 50%) of glycolide, D10 particle size (the volume content of particles smaller than this particle size accounts for 10% of all particles), and D90 particle size (the volume content of particles smaller than this particle size accounts for 90% of all particles). Isopropanol is used as the dispersion medium.

[0079] The method for measuring the acid content of crude glycolide and glycolide in the present invention is as follows:

[0080] The acid content in the crude glycolide is measured by an acid-base titration method. The specific operation is as follows: Dissolve the crude glycolide sample in about 30 mL of dry dimethyl sulfoxide. After it is dissolved, a few drops of bromophenol blue indicator solution are added thereto, and the solution is yellow. Titrate it with a dilute solution of sodium hydroxide in benzyl alcohol with a known concentration. The end point is when the solution color changes from yellow to green. Calculate the content of terminal carboxyl groups (unit: μmol) in glycolide by calculating the volume of sodium hydroxide solution used at the end point of the titration, and divide it by the mass of the crude glycolide sample to obtain the acid content of the crude glycolide (unit: μmol / g).

[0081] The method for measuring the purity of glycolide in the present invention is as follows:

[0082] The purity of glycolide was determined by gas chromatography (GC). 200 mg of the glycolide sample to be measured and 40 mg of p-chlorobenzophenone as the internal standard substance were dissolved in 10 ml of acetone. 2 μl of the dissolved solution was injected into the gas chromatograph to measure the amount of glycolide. The glycolide purity was obtained using a standard calibration curve prepared in advance with glycolide standard samples (at least 5 points between 160 - 200 mg) and the internal standard substance (40 mg), i.e., p-chlorobenzophenone. The measuring device was Agilent 7890B, the chromatographic column was a capillary column HP-5 (30 m × 0.32 mm, 0.25 μm), the column temperature was 280 °C, the injection port temperature was 150 °C, and the detector was FID.

[0083] The method for measuring the content of glycolic acid oligomers in crude glycolide and glycolide in the present invention is as follows:

[0084] 5 g of the crude glycolide or purified glycolide sample was dissolved in 50 g of dry ethyl acetate at a dissolution temperature of 25 °C. After the glycolide was completely dissolved, the solution was centrifuged at high speed (centrifugation speed 10000 rpm, centrifugation time 10 min) to allow the insoluble matter in the solution to fully sediment. After discarding the supernatant after centrifugation, 20 g of dry ethyl acetate was added to the sediment and mixed thoroughly at a mixing temperature of 25 °C to dissolve the residual glycolide. Then it was centrifuged at high speed again and the supernatant after centrifugation was discarded. The sediment was dried in vacuo (for 4 hours at 40 °C) and weighed, and dividing by the mass of the crude glycolide or glycolide sample gave the content of glycolic acid oligomers.

[0085]

Example 1

[0086] Preparation of the solid-liquid mixture:

[0087] 400.0 g of glycolide (commercially available, white powder, residual ethyl acetate content 167 ppm) and 800.0 g of absolute ethanol (dehydrated with 4A molecular sieve to a water content of 10 ppm) were added to a 2 L glass reactor to prepare a solid-liquid mixture with a solid phase mass fraction of 32.8%. The median diameter of the solid phase in the solid-liquid mixture was 455 microns, and the liquid level in the reactor (total liquid height) was 200 mm.

[0088] Mixing, sedimentation, and separation:

[0089] The internal temperature was controlled at 25 °C through the jacket water. The double-layer propeller was started, and the stirring speed was 350 rpm. Samples were taken from near the liquid surface and the bottom of the kettle to measure the density of the solid-liquid mixture, and the density deviation was 11.7%. After 1 min, the stirring was stopped, and the particles began to settle. After 1 min, the upper suspension was withdrawn from the reaction kettle within 10 seconds using a hose inserted to a liquid level of 130 mm and a pneumatic diaphragm pump. The median diameter of the solid phase in the suspension was 23 microns, and the proportion of particles with a slow sedimentation rate in all the solid phase in the solid-liquid mixture was 2.13 wt%.

[0090] Solid-liquid separation and drying:

[0091] Filter the remaining solid-liquid mixture and suspension by suction filtration, collect the wet filter cakes separately, and then place them in a vacuum dryer at 50 °C for 4 hours respectively to obtain purified glycolide and glycolide separated during the sedimentation process.

[0092] The test results are shown in Table 1.

[0093] Table 1

[0094]

[0095]

Example 2

[0096] Preparation of solid-liquid mixture:

[0097] Add 400.0 g of glycolide (commercially available, white powder, residual ethyl acetate content 167 ppm) and 800.0 g of absolute ethanol (dehydrated with 4A molecular sieve to a water content of 10 ppm) to a 2 L glass reactor to prepare a solid-liquid mixture with a solid mass fraction of 32.8%. The median diameter of the solid phase in the solid-liquid mixture is 455 microns, and the liquid level in the reactor (total liquid level height) is 200 mm.

[0098] Mixing, sedimentation and separation:

[0099] Control the internal temperature at 25 °C through the jacket water, start the double-layer propeller, and the stirring speed is 350 rpm. Samples are taken from near the liquid surface and the bottom of the kettle to test the density of the solid-liquid mixture, and the density deviation is 11.7%. After 1 minute, stop stirring, and the particles start to settle. After 30 seconds, use a hose inserted to a liquid level of 100 mm and a pneumatic diaphragm pump to precipitate the upper suspension from the reaction kettle within 10 seconds. The median diameter of the solid phase in the suspension is 48 microns, and the proportion of particles with a slow sedimentation rate in all the solid phases in the solid-liquid mixture is 4.83% by weight.

[0100] Solid-liquid separation and drying:

[0101] Filter the remaining solid-liquid mixture and suspension by suction filtration, collect the wet filter cakes separately, and then place them in a vacuum dryer at 50 °C for 4 hours respectively to obtain purified glycolide and glycolide separated during the sedimentation process.

[0102] The test results are shown in Table 2.

[0103] Table 2

[0104]

[0105]

Example 3

[0106] Preparation of molten crude glycolide:

[0107] After adding 1200 g of glycolic acid crystals and 12 g of stannous octoate catalyst into the reactor, the temperature was raised from room temperature to 90 °C. After the solid was completely dissolved, the temperature was raised to 120 °C and atmospheric pressure prepolymerization was started. After 2 h of prepolymerization, the temperature was raised to 210 °C. After no water was distilled out, the system maintained the temperature and started to evacuate. The vacuum degree was controlled at 2 kPa during this process. After no water was distilled out, 950 g of glycolic acid oligomer was obtained;

[0108] The oligomer was fed into the depolymerization reactor. The depolymerization system reacted at a reaction temperature of 285 °C, a vacuum degree of 1 kPa, and a stirring speed of 120 rpm to prepare crude glycolide. The crude glycolide vapor produced by the depolymerization reactor was condensed using a spherical condenser with a jacket water temperature of 85 °C to obtain molten crude glycolide. After 2 hours of reaction, the reaction was stopped, and 804 g of crude glycolide was obtained.

[0109] Preparation of solid-liquid mixture:

[0110] 480 g of the above-mentioned crude glycolide melt was kept warm in jacketed reactor A at 90 °C. In jacketed reactor B, 720 g of a mixed solvent of isopropanol and ethylene glycol dimethyl ether (isopropanol mass fraction 75%) was added, and it was stirred at 120 rpm and kept warm at 10 °C. The melt in reactor A was fed into reactor B at a rate of 70 wt% of the solvent mass per hour. During this period, the stirring rate was 600 rpm, and the internal temperature was maintained at 10 °C by controlling the jacket water. After completion, a solid-liquid mixture with a solid phase mass fraction of 35.1 wt% was obtained. The median diameter of the solid phase in the solid-liquid mixture was 284 microns, and the liquid level in the reactor (total liquid level height) was 195 mm.

[0111] Mixing, sedimentation, and separation:

[0112] Samples were taken near the liquid level and at the bottom of jacketed reactor B to test the density of the solid-liquid mixture, and the density deviation was 14.9%. The stirring was stopped, and the particles began to settle. After 30 seconds, the upper suspension was withdrawn from the reactor within 10 seconds using a hose inserted to a liquid level of 100 mm and a pneumatic diaphragm pump. The median diameter of the solid phase in the suspension was 55 microns, and the proportion of particles with a slow sedimentation rate in all the solid phases in the solid-liquid mixture was 9.82 wt%.

[0113] Solid-liquid separation and drying:

[0114] The remaining solid-liquid mixture and suspension were filtered by suction, and the wet filter cakes were collected separately. Then they were placed in a vacuum dryer at 50 °C for 4 hours respectively to obtain purified glycolide and glycolide separated during the sedimentation process.

[0115] The test results are shown in Table 3.

[0116] Table 3

[0117]

[0118]

Example 4

[0119] Preparation of crude glycolide solid phase:

[0120] The steps to obtain crude glycolide are the same as those in Example 3. The difference from Example 3 is that a spherical condenser with a jacket water temperature of 7°C is used to condense the crude glycolide vapor produced by the depolymerization reactor to obtain 812 g of crude glycolide solid phase.

[0121] Preparation of solid-liquid mixture:

[0122] 480 g of the above-mentioned crude glycolide solid state and 720 g of n-propanol are put into jacketed reactor B, stirred at 800 rpm, and kept at 40°C. After 1 hour, a solid-liquid mixture with a solid mass fraction of 36.6 wt% is obtained. The median diameter of the solid phase in the solid-liquid mixture is 217 microns, and the liquid level of the reactor (total liquid level height) is 200 mm.

[0123] Mixing, sedimentation and separation:

[0124] Samples are taken from near the liquid level of jacketed reactor B and the bottom of the kettle respectively to test the density of the solid-liquid mixture, and the density deviation is 8.0%. Stop stirring, and the particles start to settle. After 30 seconds, the upper suspension is precipitated from the reactor within 10 seconds using a hose inserted to a liquid level of 120 mm and a pneumatic diaphragm pump. The median diameter of the solid phase in the suspension is 39 microns, and the proportion of particles with a slow sedimentation rate in all the solid phases in the solid-liquid mixture is 8.65 wt%.

[0125] Solid-liquid separation and drying:

[0126] The remaining solid-liquid mixture and suspension are filtered by suction, and the wet filter cakes are collected separately, and then placed in a vacuum dryer at 50°C for 4 hours respectively to obtain purified glycolide and glycolide separated during the sedimentation process.

[0127] The test results are shown in Table 4.

[0128] Table 4

[0129]

[0130]

Example 5

[0131] Preparation of wet filter cake containing glycolide solid phase:

[0132] The wet filter cake obtained after solid-liquid separation and drying in Example 3 is stirred with n-propanol and configured to obtain a solid-liquid mixture, and then sedimented and separated. The remaining solid-liquid mixture after removing the upper suspension is filtered by suction to collect 447.5 g of wet filter cake, and the wet filter cake contains 16.4 wt% of solvent.

[0133] 358.9 g of the above-mentioned wet filter cake, 900 g of cyclohexane and ethyl acetate (80% by mass of cyclohexane) are put into the jacketed reactor B, stirred at 350 rpm, and kept at 20 °C. After 1 hour, a solid-liquid mixture with a solid mass fraction of 22.9 wt% is obtained. The median diameter of the solid phase in the solid-liquid mixture is 175 μm, and the liquid level of the reactor (total liquid level height) is 210 mm.

[0134] Mixing, sedimentation and separation:

[0135] Samples are taken near the liquid level of the jacketed reactor B and at the bottom of the reactor to measure the density of the solid-liquid mixture, and the density deviation is 6.1%. Stop stirring, and the particles start to settle. After 60 seconds, the upper suspension is withdrawn from the reactor within 10 seconds using a hose inserted to a liquid level of 100 mm and a pneumatic diaphragm pump. The median diameter of the solid phase in the suspension is 18 μm, and the proportion of particles with a slow sedimentation rate in all the solid phases in the solid-liquid mixture is 5.35 wt%.

[0136] Solid-liquid separation and drying:

[0137] The remaining solid-liquid mixture and suspension are filtered by suction, and the wet filter cakes are collected separately, and then placed in a vacuum dryer at 50 °C for 4 hours respectively to obtain purified glycolide and glycolide separated during the sedimentation process.

[0138] The test results are shown in Table 5.

[0139] Table 5

[0140]

[0141]

Example 6

[0142] Preparation of purified refined glycolide:

[0143] 342.9 g of the purified glycolide obtained in Example 4 (containing 340 ppm of n-propanol) and 857.1 g of ethyl acetate are put into the jacketed reactor B, stirred at 350 rpm, and kept at 50 °C. After 1 hour, a glycolide solution is obtained. Control the temperature of the jacket water to cool the solution at a cooling rate of 15 °C / h to 5 °C, so that the glycolide crystals recrystallize and precipitate, and continue to keep warm at 5 °C for 30 min to obtain a solid-liquid mixture with a solid mass fraction of 23.3 wt%. The median diameter of the solid phase in the solid-liquid mixture is 430 μm.

[0144] Mixing, sedimentation and separation:

[0145] Samples were taken from near the liquid level and the bottom of the jacketed reactor B to test the density of the solid-liquid mixture, and the density deviation was 17.5%. Under stirring at 350 rpm, the solid-liquid mixture was fed through a centrifugal pump to the bottom inlet of a tubular centrifuge (rotating speed 3000 rpm, inner cylinder diameter 100 mm). A suspension was obtained from the top clear liquid outlet of the centrifuge. The median diameter of the solid phase was 37 μm, and the proportion of particles with a slow sedimentation rate in all the solid phases in the solid-liquid mixture was 3.12% by weight.

[0146] Solid-liquid separation and drying:

[0147] The remaining solid-liquid mixture in the inner cylinder and the suspension collected from the clear liquid outlet were filtered by suction, and the wet filter cakes were collected separately. Then they were placed in a vacuum dryer at 50 °C for 4 hours respectively to obtain purified glycolide and glycolide separated during the sedimentation process respectively.

[0148] The test results are shown in Table 6.

[0149] Table 6

[0150]

[0151]

Example 7

[0152] Preparation of the solid-liquid mixture obtained after the evaporation crystallization operation of the glycolide solution:

[0153] 300.0 g of the purified glycolide (containing 81 ppm of ethyl acetate) obtained in Example 6 and 900 g of acetone were put into the jacketed reactor B, stirred at 350 rpm, and kept at 25 °C. After 1 hour, a glycolide solution was obtained. The temperature of the jacket water was controlled to keep the internal temperature at 25 °C, and stirring at 350 rpm was maintained. The solution was evaporated under an absolute pressure of 20 kPa to remove 60% of the solvent, causing the glycolide crystals to recrystallize. 540 g of isopropanol was added to the jacketed reactor B to make the solid-liquid mixture easy to transport, and a solid-liquid mixture with a solid mass fraction of 20.5 wt% was obtained. The median diameter of the solid phase in the solid-liquid mixture was 257 μm.

[0154] Mixing, sedimentation and separation:

[0155] Samples were taken from near the liquid level and the bottom of the jacketed reactor B to test the density of the solid-liquid mixture, and the density deviation was 12.3%. Under stirring at 350 rpm, the solid-liquid mixture was fed through a centrifugal pump to the bottom inlet of a tubular centrifuge (rotating speed 5000 rpm, inner cylinder diameter 100 mm). A suspension was obtained from the top clear liquid outlet of the centrifuge. The median diameter of the solid phase was 22 μm, and the proportion of particles with a slow sedimentation rate in all the solid phases in the solid-liquid mixture was 1.9% by weight.

[0156] Solid-liquid separation and drying:

[0157] Filter the remaining solid-liquid mixture in the inner cylinder and the suspension collected at the clear liquid outlet, collect the wet filter cakes separately, and then place them in a vacuum dryer at 50°C for 4 hours respectively to obtain purified glycolide and glycolide separated during the sedimentation process respectively.

[0158] The test results are shown in Table 7.

[0159] Table 7

[0160]

[0161]

Example 8

[0162] Preparation of molten crude glycolide: The same as Example 3.

[0163] Preparation of solid-liquid mixture: The same as Example 3.

[0164] Sedimentation and solid-liquid separation:

[0165] Transfer the solid-liquid mixture with a solid phase mass fraction of 35.1 wt% to the jacketed sintered glass funnel C (jacket water temperature 10°C, sintered glass pore size 15 microns). The particles start to settle. After 600 seconds, evacuate the receiving container connected to the sintered glass funnel to 5 kPaA for solid-liquid separation. After 1 hour, no filtrate flows through the sintered glass into the receiving container, and a wet filter cake is obtained. The height of the wet filter cake in the container is 51.0 mm (the height from the upper surface of the sintered glass is the height). Use a spatula to remove the wet filter cake layer above 48.0 mm from the container. The particles in the removed wet filter cake are the particles with a slow sedimentation rate. The proportion of the particles with a slow sedimentation rate in the total solid phase weight of the solid-liquid mixture is 7.12 wt%, and the median diameter of the solid phase of the removed particles is 46 microns.

[0166] Drying:

[0167] Collect the remaining wet filter cake and the scraped wet filter cake separately and place them in a vacuum dryer at 50°C for 4 hours respectively to obtain purified glycolide and glycolide separated during the sedimentation process respectively.

[0168] The test results are shown in Table 8.

[0169] Table 8

[0170]

[0171] Examples 1 to 8 can handle the solid-liquid mixture containing glycolide obtained from various sources in the prior art. The treatment method is simple, can quickly and efficiently remove the oligomer impurities in glycolide, and has the advantages of low content of oligomer impurities and high purity of glycolide after purification. It is proved that the present invention makes the solid-liquid mixture containing glycolide and an organic solvent fully mixed and then performs particle sedimentation, and then removes the particles with a slow sedimentation rate from the solid phase and collects the remaining solid phase. The obtained solid phase has a low content of glycolic acid oligomer impurities, simple operation, and great industrial application value.

Claims

1. A method for purifying glycolide, comprising the following steps: (1) Thoroughly mix the solid-liquid mixture evenly and allow the particles therein to settle, remove the particles with a slow settling rate, and recover the remaining solid-phase particles to obtain purified glycolide; the solid-liquid mixture comprises a glycolide solid phase and a glycolide saturated solution; Optionally, (2) dry the solid phase recovered in step (1).

2. The method for purifying glycolide according to claim 1, wherein: The proportion of the particles with a slow settling rate in the total solid phase weight of the solid-liquid mixture is less than or equal to 10% by weight, preferably 1-10% by weight; and / or, The median diameter of the particles with a slow settling rate is less than or equal to 90 microns, preferably less than or equal to 60 microns; and / or, The content of oligomer impurities in the particles with a slow settling rate is greater than or equal to 1% by weight, preferably greater than or equal to 2.5% by weight, more preferably greater than or equal to 4% by weight.

3. The method for purifying glycolide according to claim 1, wherein: In step (1), The solid-liquid mixture is obtained by adding the molten crude glycolide to an organic solvent in at least one of the ways of dropping, injecting, spraying, showering, and spraying; preferably, The molten crude glycolide is unpurified molten crude glycolide and / or purified molten crude glycolide; and / or, The mass content of glycolide in the molten crude glycolide is 85% - 99%.

4. The method for purifying glycolide according to claim 1, wherein: In step (1), The solid-liquid mixture is obtained by adding the crude glycolide solid phase to an organic solvent; preferably, The crude glycolide solid phase is obtained by condensing and solidifying the molten crude glycolide.

5. The method for purifying glycolide according to claim 1, wherein: In step (1), The solid-liquid mixture is obtained by mixing the glycolide solid phase with an organic solvent; preferably, the glycolide solid phase is a wet filter cake or purified glycolide after drying treatment.

6. The method for purifying glycolide according to claim 1, wherein: In step (1), The solid-liquid mixture is obtained by cooling crystallization or evaporation crystallization of the glycolide solution; preferably, the glycolide solution is a solution formed by dissolving molten or solid-phase crude glycolide in an organic solvent.

7. The method for purifying glycolide according to any one of claims 3 - 6, wherein: The organic solvent is at least one of acetone, ethyl acetate, ethylene glycol dimethyl ether, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, n-pentanol, isopentanol, n-hexane, cyclohexane, pentane, and petroleum ether.

8. The method for purifying glycolide according to claim 1, wherein: In step (1), The mass fraction of the solid phase in the solid-liquid mixture is less than or equal to 50%, preferably less than or equal to 40%, more preferably 5 - 40%, and most preferably 20 - 40%; and / or, The median diameter of the solid phase in the solid-liquid mixture is less than or equal to 600 microns, preferably less than or equal to 500 microns; and / or, The liquid phase of the solid-liquid mixture is a saturated solution of glycolide in an organic solvent; and / or, The term "uniform" means that the density deviation between any parts of the solid-liquid mixture does not exceed 30%, preferably does not exceed 20%.

9. The method for purifying glycolide according to claim 1, wherein: Step (1), The manner of particle sedimentation is that the particles sediment in at least one of gravity, centrifugal force, and convection; and / or, The manner of removing the particles with slow sedimentation rate is to separate a part of the solution containing the particles with slow sedimentation rate from the solid-liquid mixture or to separate the solid phase after separating the particles with slow sedimentation rate from the solid-liquid mixture; and / or, The method for recovering the remaining solid-phase particles is centrifugation or filtration; and / or, The solid-phase drying method in step (2) is convective drying under a thermally inert gas or heat conduction drying under vacuum.

10. The method for purifying glycolide according to claim 1, wherein: Steps (1) and optionally step (2) are repeated at least once.

11. A glycolide prepared by the purification method according to any one of claims 1 to 10.

12. An application of the glycolide according to claim 11 in the preparation of polyglycolic acid.

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