METHOD FOR PURIFYING GLYCOLIDE AND GLYCOLIDE OBTAINED THEREFROM

Abstract

The present invention provides a method for purifying glycolide and glycolide obtained therefrom. The method includes extracting impurities from crude glycolide using solvent A and then recrystallizing using solvent B, where solvent A contains at least two solvents that are miscible with each other. In the method of the present invention, two polar solvents are used to purify crude glycolide. This method has a good extraction effect on acidic impurities such as glycolic acid oligomers. The solvent is easily and completely removed during solid-liquid separation and drying. The problem of solvent residue in the purified product is solved. The technical effect of a low free acid content in the product is achieved. The technical solution of the present invention has the technical advantages of easy solvent recovery and a low free acid content in the product.

Description

Detailed Description of the Invention

[0001] [Technical Field] The present invention relates to the field of glycolides, and in particular to a method for purifying glycolide and glycolides obtained therefrom.

[0002] [Background technology] Polyglycolic acid (PGA) is a synthetic polymer material with good biodegradability and biocompatibility. Unlike conventional polymeric materials such as plastics and rubber, which have stable properties, PGA gradually degrades over time and eventually transforms into water and carbon dioxide, which are harmless to humans, animals, plants, and the natural environment. The applications of PGA are primarily evident in two areas: biomedicine and ecology.

[0003] Glycolide is a cyclic dimer of glycolic acid, i.e., a cyclic substance formed by the dehydration and condensation of two glycolic acid molecules. Ring-opening polymerization of glycolide is a relatively mature method for preparing polyglycolic acid, which can yield polyglycolic acid products with higher relative molecular weights. Currently, the most mature and widely used glycolide synthesis process both domestically and internationally is primarily a polycondensation-depolymerization process using glycolic acid as the raw material.

[0004] CN105272958A discloses a process for preparing glycolide, which is an example of using a polycondensation-depolymerization process to prepare crude glycolide. First, glycolic acid is gradually heated to a maximum temperature of 200°C under atmospheric pressure to carry out the polycondensation reaction, and the water generated during the reaction is removed. After the amount of water generated reaches a certain level, the water is further removed under reduced pressure to obtain a polycondensation product with a higher molecular weight. Next, glycolic acid prepolymer and stannous octoate (a transesterification catalyst added before prepolymerization) are heated to a temperature of 230°C to 290°C under an ultra-high vacuum of 0.1 to 1 kPa. The glycolide vapor generated during the reaction is collected and cooled to produce a crude product as a yellow solid.

[0005] The crude glycolide obtained from the above depolymerization reaction typically contains various impurities, such as water, glycolic acid, glycolic acid oligomers (with a molecular weight less than 500 g / mol), and polyglycolic acid (with a molecular weight greater than 500 g / mol). The presence of a very small amount of active hydrogen in the ring-opening polymerization of lactide significantly affects the molecular weight of the resulting polymer. Polyglycolic acid, which must meet the requirements for surgical sutures, must have an intrinsic viscosity of 1 or greater and a weight-average molecular weight of more than 100,000. Therefore, to obtain a high-purity glycolide product, it is necessary to purify the crude glycolide to remove as many impurities as possible.

[0006] In addition, it is worth noting that the use of solvents in the process of preparing refined glycolide from crude glycolide inevitably introduces traces of solvent molecules into the glycolide product. These solvent molecules are likely to contain active hydrogen, which can adversely affect the polymerization reaction of glycolide. During the glycolide polymerization process, traces of solvent molecules remain in the PGA, which can affect its biomedical application in the human body. Therefore, it is very important to use appropriate methods to resolve the issue of solvent residues in the refined product.

[0007] Existing glycolide purification techniques primarily involve recrystallization (cooling recrystallization and evaporation recrystallization) and alcohol washing. Recrystallization is the most commonly used method, and the most common method involves repeatedly recrystallizing crude glycolide using ethyl acetate as the organic solvent. Because these organic solvents are suitable for glycolide, which has a high molecular affinity with these solvents, it is difficult to completely remove the solvent from the purified glycolide after drying. For example, the residual ethyl acetate content can reach 500 ppm or more after thorough drying, which means that ethyl acetate remains in the polymer PGA after the polymerization reaction.

[0008] In addition to the technical solution of multiple recrystallization with ethyl acetate to purify glycolide, the prior art also includes a technical solution of coupling recrystallization with alcohol washing to purify glycolide. For example, Patent CN107868075A discloses a process for purifying glycolide, in which crude glycolide is purified by a technical solution including cooling recrystallization, mixing with an anti-solvent, washing, filtration, and drying. This technical solution can sufficiently reduce the solvent residue because the residual solvent for glycolide becomes alcohol during the final drying, which is considered to be an anti-solvent for glycolide. However, the process of mixing with an anti-solvent mainly removes impurities adsorbed on the surface of glycolide crystal particles, but hardly removes impurity crystal nuclei embedded in the crystals. Therefore, the effect of the mixed washing on the purification of impurities is not as good as that of recrystallization, resulting in a terminal carboxyl content of 1.0 × 10 in the final purified glycolide product. -5 It is difficult to reduce the concentration of the crude glycolide to 5.2×10 mol / g or less. In addition, when the quality of the crude glycolide is poor, for example, when the crude glycolide purity is less than 85% or the terminal carboxyl content is less than 5.2×10 -4 When the content exceeds mol / g, purifying crude glycolide using only the alcohol compound does not produce a good effect.

[0009] [Summary of the Invention] The technical problem that the present invention aims to solve is the problem that the amount of residual solvent in the purified glycolide obtained by the existing crude glycolide purification process is relatively high. The present invention provides a purification technical solution that is different from the technical solution of coupling recrystallization and washing, which has technical advantages such as easy solvent recovery and low free acid content in the product.

[0010] An object of the present invention is to provide a method for purifying glycolide, which comprises extracting impurities from crude glycolide with solvent A and then recrystallizing with solvent B, wherein solvent A comprises at least two solvents, and the solvents are miscible with each other. By adjusting the combined sequence of recrystallization-washing in the prior art, the impurities trapped by recrystallization can be significantly reduced, and a better overall purification effect can be achieved.

[0011] Preferably, the method for purifying glycolide comprises the steps of: (1) Crude glycolide and solvent A are mixed and stirred, the resulting solid-liquid mixture is filtered, and the resulting filter cake is recovered; (2) Mixing the filter cake obtained in step (1) with solvent B, heating the resulting mixture, and then cooling the resulting solution to separate glycolide crystals, and recovering the resulting filter cake by filtration; Preferably, to produce purified glycolide, step (2) is repeated at least once, and the resulting filter cake is then vacuum dried.

[0012] In step (1), the mixing temperature is 0 to 40°C, preferably 0 to 20°C.

[0013] In step (2), the temperature to which the resulting mixture is heated is 70 to 80°C, preferably 75 to 80°C, and the temperature to which the resulting solution is cooled is 0 to 25°C, preferably 15 to 25°C.

[0014] According to a preferred embodiment of the present invention, the method for purifying crude glycolide includes the steps of: (1) mixing and stirring crude glycolide with solvent A, then filtering the resulting solid-liquid mixture, and recovering the resulting filter cake; (2) dissolving the filter cake obtained in step (1) in solvent B at a constant temperature of 70-80°C, cooling the resulting solution to 0-25°C to separate glycolide crystals, and recovering the resulting filter cake by filtration; and (3) repeating step (2) at least once, and then vacuum-drying the resulting filter cake to produce a purified glycolide product.

[0015] In any of the above technical solutions, the solvent A is a mixed solvent of solvent I and solvent II, solvent I is selected from polyalcohol ethers having a boiling point of 180°C or higher at atmospheric pressure, solvent II is selected from saturated alcohols having a boiling point of 120°C or lower at atmospheric pressure, solvent I is preferably selected from at least one polyalkylene glycol ether, and solvent II is preferably selected from at least one saturated monohydric alcohol.

[0016] The solvent B is selected from saturated alcohols having a boiling point of 120° C. or less at atmospheric pressure, preferably from at least one saturated monohydric alcohol, and the solvent B and solvent II may be the same or different.

[0017] In any of the above technical solutions, the solvents I, II and B are all polar solvents, and are subjected to techniques such as azeotropic dehydration or molecular sieve adsorption dehydration before contacting the crude glycolide, so that the water content is less than 40 ppm.

[0018] In any of the above technical solutions, Solvent A is a homogeneous liquid at room temperature, and the components therein are miscible. The mass fraction of Solvent II in Solvent A is 50% or more, but not equal to 100%, preferably 50-80%, i.e., the proportion of Solvent I, which has a higher boiling point, in Solvent A is limited. This not only ensures that all Solvent I enters the liquid phase through several solid-liquid separation processes and does not remain in glycolide, but also prevents glycolide from dissolving in the solvent as the amount of Solvent I used increases, resulting in unacceptable losses in purification yield.

[0019] In any of the above technical solutions, the solvent I is selected from at least one of polyalkylene glycol monoethers or polyalkylene glycol diethers. From the viewpoints of easy access to raw materials and ease of synthesis, polyethylene glycol ether is preferred. In consideration of the solubility of solvent I in saturated monohydric alcohols and its fluidity, the polyethylene glycol ether is preferably polyethylene glycol diether. The degree of polymerization of ethylene glycol in the polyethylene glycol diether is preferably 20 or less, more preferably 10 or less. The ether groups at both ends of the polyethylene glycol diether are preferably both methyl groups or alkyl groups having 2 to 7 carbon atoms, more preferably both methyl groups.

[0020] In any of the above technical solutions, the polyethylene glycol diether is preferably at least one of pentaethylene glycol dimethyl ether, hexaethylene glycol dimethyl ether, heptaethylene glycol dimethyl ether, octaethylene glycol dimethyl ether, nonaethylene glycol dimethyl ether, etc.

[0021] In any of the above technical solutions, the solvent II is selected from at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, and isobutyl alcohol.

[0022] In both of the above technical solutions, solvent II has a higher dissolving capacity for water and some small molecule impurities, such as glycolic acid, but a limited dissolving capacity for other impurities, such as glycolic acid oligomers (having a molecular weight of less than 500 g / mol) and polyglycolic acid (having a molecular weight of more than 500 g / mol). To better remove the latter two acidic impurities, solvent I is added to solvent A because it has a good dissolving capacity for the latter two impurities. In purification step (2), most of the glycolide is present in a solid form in the solid-liquid mixture, and a small amount of glycolide is dissolved in the solvent, which enters the filtrate during filtration along with various impurities dissolved in the solvent. The filter cake is the glycolide purified in step (1), and various impurities have been significantly reduced, reducing the burden of cooling crystallization in step (2).

[0023] In any of the above technical solutions, the solvent B is selected from at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, and isobutyl alcohol.

[0024] In any of the above technical solutions, crude glycolide is obtained by depolymerization of polyglycolic acid and / or polyglycol ester, for example, crude glycolide can be obtained by polycondensation-depolymerization of glycolic acid (ester), or can be obtained by depolymerization of waste polyglycolic acid (PGA), and preferably the purity of glycolide therein is 75 wt% or more and less than 95 wt%.

[0025] In both of the above technical solutions, the purity of crude glycolide is measured by gas chromatography (GC). The impurities in crude glycolide are mainly water, glycolic acid, glycolic acid oligomers (molecular weight less than 500 g / mol), and polyglycolic acid (molecular weight higher than 500 g / mol). Among these impurities, glycolic acid oligomers and polyglycolic acid are easily soluble in solvent I, and these impurities are separated from glycolide during the filtration process of the solid-liquid mixture in step (1). Small molecules such as water and glycolic acid have similar polarity to solvent II and therefore dissolve in solvent A. They do not separate solids during cooling and crystallization, and can be separated from glycolide by the filtration operations in steps (1) and (2).

[0026] In any of the above technical solutions, crude glycolide and solvent A in step (1) are mixed and stirred at a constant temperature of 0 to 40°C. The preferred constant temperature range is 0 to 20°C. If the washing temperature is higher than 40°C, the glycolide dissolved in mixed solvent A will cause a significant loss of purification yield; if the washing temperature is too low, the effect of extracting impurities with solvent A will not be ideal.

[0027] In any of the above technical solutions, the mass ratio of the crude glycolide to solvent A in step (1) is (0.5-5):1, preferably (0.5-2):1. If the mass ratio is higher, the washing effect will be reduced; if the mass ratio is lower, the glycolide dissolved in solvent A may cause unacceptable loss of purification yield.

[0028] In any of the above technical solutions, the filter cake obtained by filtering the solid-liquid mixture in step (1) should have as low a water content as possible to minimize the amount of higher boiling point solvent I remaining in the filter cake. The preferred water content is 10% or less, more preferably 5% or less.

[0029] The filtration operation in step (1) can be carried out in a nitrogen pressure filter, a plate and frame pressure filter, or a centrifugal pressure filter, preferably in a plate and frame pressure filter or a centrifugal pressure filter, more preferably in a plate and frame pressure filter.

[0030] In both of the above technical solutions, the solvent in the filtrate obtained by filtering the solid-liquid mixture in step (1) is easily recovered. Given the large difference in boiling points between solvents I and II, solvents I and II can be efficiently separated by fractional distillation. Solvent II, the light component in the fractional distillation, is first distilled off and recovered, and can be reused in any rectification and any necessary post-dehydration purification steps. Preferably, in step (1), the heavy component remaining after distillation of the light component is homogeneous, has good fluidity, and is transparent. When placed at 4°C, no solids separate, indicating that solvent I has a high ability to dissolve acidic impurities. The heavy component can be extracted with an organic solvent such as cyclohexane, which forces solvent I into the liquid phase and allows it to be reused in step (1) after solid-liquid separation and fractionation.

[0031] In any of the above technical solutions, the constant temperature in step (2) should not exceed the boiling point of solvent B, and preferably should be at least 3°C ​​lower than the boiling point to ensure complete dissolution of the glycolide component in the filter cake in step (1). The temperature to which the material is heated is preferably 70-80°C, more preferably 75-80°C.

[0032] In any of the above technical solutions, in step (2), the mass ratio of the filter cake to solvent B is (0.05-5):1, preferably (0.1-1):1.

[0033] In any of the above technical solutions, the end temperature of cooling crystallization in step (2) is 0 to 25°C, preferably 15 to 25°C. In the preferred temperature range, the solubility of glycolide in solvent B is extremely low, and most of the glycolide has already crystallized and separated in this temperature range. Further lowering the end temperature of cooling crystallization beyond the preferred temperature range increases the load of low-temperature water consumption and the energy consumption of the process, but does not significantly improve the crystallization yield of glycolide.

[0034] In any of the above technical solutions, when the glycolide crystals are collected by filtration after cooling and crystallization in step (2), the pore size of the filter screen should be 200 microns or less to reduce the loss of crystals during filtration, and the pore size of the filter screen should be 50 microns or more to facilitate the separation of other granular impurities from glycolide that pass through the filter screen.

[0035] The filter cake obtained by filtration in step (2) should have as low a moisture content as possible, preferably 10% or less, more preferably 5% or less, and the filtration operation can be carried out using a nitrogen pressure filter, a plate frame pressure filter, or a centrifugal pressure filter, preferably a plate frame pressure filter or a centrifugal pressure filter, more preferably a plate frame pressure filter.

[0036] In both of the above technical solutions, the cooling rate after glycolide nucleation during cooling and crystallization in step (2) is 5-10°C / hour, and the stirring mode after nucleation is intermittent stirring with a rotation speed not exceeding 20 rpm. The lower cooling rate is for complete and uniform crystal growth, and the use of low rotation speed and intermittent stirring is to ensure uniform heat transfer during material cooling.

[0037] In any of the above technical solutions, the drying temperature under vacuum does not exceed 40°C, and the preferred drying temperature is 20-30°C. Within the preferred drying temperature range, the glycolide crystals are preferably in a fluidized state during vacuum drying. Therefore, the vacuum drying is preferably carried out in a double-cone rotary vacuum dryer.

[0038] A second object of the present invention is to provide a purified glycolide obtained by said process.

[0039] The terminal carboxyl content of the purified glycolide obtained in the present invention is 1 to 10 μmol / g, preferably 2 to 5 μmol / g.

[0040] The technical solution of the present invention introduces a polyalkylene glycol ether into the washing of crude glycolide in saturated monohydric alcohol, so that the acidic impurities (having a molecular weight of approximately 500 g / mol) in the crude glycolide are completely extracted by the washing solvent, reducing the purification load in the subsequent recrystallization process. Compared with the prior art, the resulting purified glycolide has a lower terminal carboxyl content. The polyalkylene glycol ether used in the technical solution of the present invention is miscible with saturated monohydric alcohol in a certain ratio, and can be easily separated from glycolide during the solid-liquid separation process of the solvent and glycolide, without remaining in the final purified product. According to the technical solution of the present invention, the saturated monohydric alcohol is separated from glycolide by drying to obtain a purified glycolide product, and the saturated monohydric alcohol is easily removed, thereby solving the problem of solvent residue in the purified product.

[0041] Existing refined glycolide is typically obtained by recrystallizing crude glycolide several times in a good solvent, such as ethyl acetate, followed by filtration and drying. Because glycolide has a high affinity for good solvents at the molecular level, it is difficult to completely remove the solvent from the refined glycolide after drying. This results in residual refined solvent in the polymer PGA after the ring-opening polymerization reaction, which affects the biomedical application of PGA in the human body. In the technical solution of the present invention, two types of polar solvents are used to purify crude glycolide. This has a good extraction effect on acidic impurities such as glycolic acid oligomers. The solvent is easily and completely removed during the solid-liquid separation and drying process. This solves the problem of solvent residue in the refined product. The technical effect of a low free acid content in the product is achieved. The technical solution of the present invention has the technical advantages of easy solvent recovery and a low free acid content in the product.

[0042] Detailed Description The present invention will be specifically described below by taking specific embodiments.It should be pointed out here that the following examples / embodiments are only used to further explain the present invention and cannot be construed as limiting the protection scope of the present invention.Those skilled in the art can understand that some non-essential improvements and modifications to the present invention made according to the content of the present invention still fall within the protection scope of the present invention.

[0043] The raw materials used in certain embodiments / embodiments of the present invention are commercially available.

[0044] The method for measuring the free acid concentration of crude glycolide or glycolide of the present invention is as follows: The concentration of free acid in crude glycolide is determined by acid-base titration. Specifically, a crude glycolide sample is dissolved in approximately 30 mL of dry dimethyl sulfoxide, and several drops of bromophenol blue indicator solution are added to turn the solution yellow. A dilute solution of sodium hydroxide in benzyl alcohol is titrated with a known concentration, and the endpoint is determined when the color of the solution changes from yellow to green. The amount of terminal carboxyl in glycolide (in μmol) is calculated by calculating the volume of the sodium hydroxide solution used to reach the titration endpoint and then dividing by the mass of the crude glycolide sample to obtain the concentration of free acid in crude glycolide (in μmol / g).

[0045] The purity of the crude glycolide of the present invention is determined as follows: The purity of crude glycolide was determined by gas chromatography (GC). A 200 mg sample of glycolide to be tested and 40 mg of the internal standard p-chlorobenzophenone were dissolved in 10 mL of acetone, and 2 μL of the resulting solution was injected into the gas chromatograph to measure the amount of glycolide. A pre-prepared standard calibration curve was used to measure the purity of glycolide using glycolide standard samples (at least five points between 160 and 200 mg) and an internal standard, e.g., p-chlorobenzophenone (40 mg). The instrument used was an Agilent 7890B, with a capillary column HP-5 (30 m x 0.32 mm, 0.25 μm), the column temperature was 280 °C, the inlet temperature was 150 °C, and the detector was an FID.

[0046] The purity of the purified glycolide of the present invention is determined as follows: The purity of the purified glycolide crystals is analyzed by differential scanning calorimetry (DSC). The instrument model used is a TA Discovery, and the temperature of the glycolide is increased from 65°C to 95°C at a controlled heating rate of 0.5°C / min. The software provided with the instrument is used to analyze the purity of the glycolide.

[0047] The residual solvent content in the purified glycolide of the present invention is measured by high performance liquid chromatography.

[0048] The present invention will be further illustrated by the following examples.

[0049] Example 1 Preparation of crude glycolide by polycondensation depolymerization: 600 g of glycolic acid crystals and 6 g of stannous octoate catalyst were added to a reactor, and the temperature was raised from room temperature to 90°C. After the solids were completely dissolved, the temperature was raised to 120°C to initiate prepolymerization under atmospheric pressure. After 2 hours of prepolymerization, the temperature was raised to 210°C. The system temperature was maintained until no more water was distilled, and then the system began to be evacuated. The vacuum level during this process was controlled at 3 kPa until no more water was distilled, and finally 482 g of glycolic acid oligomer was obtained.

[0050] The oligomer was fed into a depolymerization reactor and reacted at a reaction temperature of 290°C, a vacuum of 3 kPa, and a stirring speed of 100 rpm to prepare crude glycolide. After reacting for 2 hours, the reaction was stopped to obtain a first batch of crude glycolide (397 g) with an acid content of 452 μmol / g and a glycolide purity of 89.60%.

[0051] Example 2 50 g of crude glycolide obtained in Example 1 was mixed with 40 g of n-butanol (water content 30 ppm or less) and 10 g of pentaethylene glycol dimethyl ether, and the solid-liquid mixture was stirred at room temperature for 1 hour. The stirring was stopped, and the mixture was suction filtered to obtain 46 g of filter cake. The filter cake was mixed with 92 g of n-butanol, and the mixture was heated to 80 °C to form a homogeneous solution. With a rotation speed of 100 rpm, the solution was cooled to room temperature at a rate of 10 °C / h, and glycolide was separated from the system. The resulting mixture was suction filtered, and the filter cake was subjected to the above cooling, recrystallization, and filtration process once. The solid obtained by filtration was vacuum dried at 30 °C for 8 hours, yielding 37.4 g of white crystals with a total yield of 74.8%. The purity of the purified glycolide was 99.73% as measured by DSC. The terminal carboxyl content of the purified glycolide was 3.2 μmol / g as measured by acid-base titration. The amounts of n-butanol and pentaethylene glycol dimethyl ether remaining in the glycolide as measured by liquid chromatography were 0.025%, and the amount of n-butanol remaining was 225 ppm.

[0052] Example 3 50 g of crude glycolide obtained in Example 1 was mixed with 40 g of n-butanol (water content 30 ppm or less) and 10 g of nonaethylene glycol dimethyl ether, and the solid-liquid mixture was stirred at room temperature for 1 hour. Stirring was stopped, and the mixture was suction filtered to obtain 45 g of a filter cake. The filter cake was mixed with 90 g of n-butanol, and the mixture was heated to 80°C to form a homogeneous solution. With a rotation speed of 100 rpm, the solution was cooled to room temperature at a rate of 10°C / h, and glycolide was separated from the system. The resulting mixture was suction filtered, and the filter cake was subjected to the above cooling, recrystallization, and filtration process once. The solid obtained by filtration was vacuum dried at 30°C for 8 hours, yielding 36.9 g of white crystals with a total yield of 73.8%. The purity of the purified glycolide measured by DSC was 99.82%. The terminal carboxyl content of the purified glycolide was measured by acid-base titration and was 1.8 μmol / g. The remaining amounts of n-butanol and nonaethylene glycol dimethyl ether in the glycolide were measured by liquid chromatography and were 0.015% and 134 ppm, respectively.

[0053] Example 4 50 g of crude glycolide obtained in Example 1 was mixed with 40 g of isopropanol (water content 30 ppm or less) and 10 g of pentaethylene glycol dimethyl ether, and the solid-liquid mixture was stirred at room temperature for 1 hour. The stirring was stopped, and the mixture was suction filtered to obtain 44 g of a filter cake. The filter cake was mixed with 88 g of isopropanol, and the mixture was heated to 78°C to form a homogeneous solution. With a rotation speed of 100 rpm, the solution was cooled to room temperature at a rate of 10°C / h, and glycolide was separated from the system. The resulting mixture was suction filtered, and the filter cake was subjected to the above cooling, recrystallization, and filtration process once. The solid obtained by filtration was vacuum dried at 30°C for 8 hours, yielding 35.8 g of white crystals with a total yield of 71.6%. The purity of the purified glycolide was 99.83% as measured by DSC. The terminal carboxyl content of the purified glycolide was 2.6 μmol / g as measured by acid-base titration. The amounts of isopropanol and pentaethylene glycol dimethyl ether remaining in the glycolide as measured by liquid chromatography were 0.030%, and the amount of isopropanol remaining was 290 ppm.

[0054] Example 5 50 g of crude glycolide obtained in Example 1 was mixed with 40 g of isopropanol (water content 30 ppm or less) and 10 g of nonaethylene glycol dimethyl ether, and the solid-liquid mixture was stirred at room temperature for 1 hour. The stirring was stopped, and the mixture was suction filtered to obtain 44 g of filter cake. The filter cake was mixed with 88 g of isopropanol, and the mixture was heated to 78°C to form a homogeneous solution. The solution was cooled to room temperature at a rate of 10°C / h under a rotation speed of 100 rpm, and glycolide was separated from the system. The resulting mixture was suction filtered, and the filter cake was subjected to the above cooling, recrystallization, and filtration process once. The solid obtained by filtration was vacuum dried at 30°C for 8 hours, yielding 35.2 g of white crystals with a total yield of 70.4%. The purity of the purified glycolide was 99.74% as measured by DSC. The terminal carboxyl content of the purified glycolide was 2.8 μmol / g as measured by acid-base titration. The amounts of isopropanol and nonaethylene glycol dimethyl ether remaining in the glycolide as measured by liquid chromatography were 0.035%, and the amount of isopropanol remaining was 336 ppm.

[0055] Example 6 50 g of crude glycolide, obtained by the same method as in Example 1 and having an acid content of 661 μmol / g and a glycolide purity of 83.70%, was mixed with 30 g of isopropanol (water content of 30 ppm or less) and 20 g of heptaethylene glycol dimethyl ether, and the solid-liquid mixture was stirred at room temperature for 30 minutes. The stirring was stopped, and the mixture was suction filtered to obtain 42 g of a filter cake. The filter cake was mixed with 210 g of isopropanol, and the mixture was heated to 78°C to form a homogeneous solution. With a rotation speed of 100 rpm, the solution was cooled to room temperature at a rate of 10°C / h, and glycolide was separated from the system. The resulting mixture was suction filtered, and the filter cake was subjected to the above cooling, recrystallization, and filtration process once. The solid obtained by filtration was vacuum dried at 30°C for 8 hours, yielding 34.2 g of white crystals in a total yield of 68.4%. The purity of the purified glycolide measured by DSC was 99.78%. The terminal carboxyl content of the purified glycolide measured by acid-base titration was 3.1 μmol / g. The remaining amounts of isopropanol and heptaethylene glycol dimethyl ether in the glycolide measured by liquid chromatography were 0.033%, and the remaining amount of isopropanol was 318 ppm.

[0056] Example 7 50 g of crude glycolide obtained in Example 1 was mixed with 10 g of isopropanol (water content 30 ppm or less) and 2.5 g of nonaethylene glycol dimethyl ether, and the solid-liquid mixture was stirred at room temperature for 1 hour. The stirring was stopped, and the mixture was suction filtered to obtain 46 g of filter cake. The filter cake was mixed with 92 g of isopropanol, and the mixture was heated to 78°C to form a homogeneous solution. With a rotation speed of 100 rpm, the solution was cooled to room temperature at a rate of 10°C / h, and glycolide was separated from the system. The resulting mixture was suction filtered, and the filter cake was subjected to the above cooling, recrystallization, and filtration process once. The solid obtained by filtration was vacuum dried at 30°C for 8 hours, yielding 35.4 g of white crystals with a total yield of 70.8%. The purity of the purified glycolide was 99.58% as measured by DSC. The terminal carboxyl content of the purified glycolide was 5.8 μmol / g as measured by acid-base titration. The amounts of isopropanol and nonaethylene glycol dimethyl ether remaining in the glycolide as measured by liquid chromatography were 0.015%, and the amount of isopropanol remaining was 142 ppm.

[0057] Comparative Example 1 50 g of crude glycolide obtained in Example 1 was recrystallized from 50 mL of ethyl acetate (water content 30 ppm or less). The mixture was heated to 70°C to obtain a solution. The resulting solution was then filtered while hot, and the filtrate was cooled to room temperature. The solid-liquid mixture from which the crystals were separated was filtered and dried, and the recrystallization process was repeated once. The resulting solid was dried under vacuum at 30°C for 8 hours to obtain 30.4 g of white crystals for a total yield of 60.8%. The purity of the purified glycolide was determined by DSC to be 99.20%. The terminal carboxyl content of the purified glycolide was determined by acid-base titration to be 10.1 μmol / g. The residual ethyl acetate content in the glycolide was determined by liquid chromatography to be 0.090%.

[0058] Comparative Example 2 30.4 g of the purified glycolide obtained in Comparative Example 1 was recrystallized once, and the resulting solid was vacuum-dried at 30°C for 8 hours to obtain 26.5 g of white crystals. The purity of the purified glycolide was 99.7% as measured by DSC. The terminal carboxyl content in the purified glycolide was 2.3 μmol / g as measured by acid-base titration. The residual amount of ethyl acetate in the glycolide was 0.080% as measured by liquid chromatography.

[0059] Comparative Example 3 50 g of crude glycolide obtained in Example 1 was mixed with 50 g of pentaethylene glycol dimethyl ether, and the solid-liquid mixture was stirred at room temperature for 1 hour. The stirring was stopped, and the mixture was suction filtered to obtain 38 g of filter cake. The filter cake was mixed with 76 g of pentaethylene glycol dimethyl ether, and the mixture was heated to 80°C to form a homogeneous solution. With the rotation speed at 100 rpm, the solution was cooled to room temperature at a rate of 10°C / h, and glycolide was separated from the system. The resulting mixture was suction filtered, and the filter cake was subjected to the above cooling, recrystallization, and filtration process once. The solid obtained by filtration was vacuum dried at 30°C for 8 hours, yielding 27.2 g of white crystals with a total yield of 54.4%. The purity of the purified glycolide was 99.21% as measured by DSC. The terminal carboxyl content of the purified glycolide was 8.5 μmol / g as measured by acid-base titration. The residual amount of pentaethylene glycol dimethyl ether in the glycolide was measured by liquid chromatography and was found to be 0.86%.

[0060] Comparative Example 4 50 g of crude glycolide obtained in Example 1 was mixed with 50 g of n-butanol (water content 30 ppm or less), and the solid-liquid mixture was stirred at room temperature for 1 hour. The stirring was stopped, and the mixture was suction filtered to obtain 40 g of filter cake. The filter cake was mixed with 80 g of n-butanol, and the mixture was heated to 80°C to form a homogeneous solution. With a rotation speed of 100 rpm, the solution was cooled to room temperature at a rate of 10°C / h, and glycolide was separated from the system. The resulting mixture was suction filtered, and the filter cake was subjected to the cooling, recrystallization, and filtration process once. The solid obtained by filtration was vacuum dried at 30°C for 8 hours, yielding 28.3 g of white crystals with a total yield of 56.6%. The purity of the purified glycolide measured by DSC was 99.33%. The terminal carboxyl content of the purified glycolide measured by acid-base titration was 9.6 μmol / g. The amount of residual n-butanol in the glycolide was measured by liquid chromatography and was found to be 200 ppm.

[0061] Comparative Example 5 50 g of crude glycolide obtained in Example 1 was mixed with 10 g of n-butanol (water content 30 ppm or less) and 40 g of nonaethylene glycol dimethyl ether, and the solid-liquid mixture was stirred at room temperature for 1 hour. The stirring was stopped, and the mixture was suction filtered to obtain 37 g of filter cake. The filter cake was mixed with 74 g of n-butanol, and the mixture was heated to 80°C to form a homogeneous solution. With a rotation speed of 100 rpm, the solution was cooled to room temperature at a rate of 10°C / h, and glycolide was separated from the system. The resulting mixture was suction filtered, and the filter cake was subjected to the above cooling, recrystallization, and filtration process once. The solid obtained by filtration was vacuum dried at 30°C for 8 hours, yielding 27.0 g of white crystals with a total yield of 54.0%. The purity of the purified glycolide was 99.25% as measured by DSC. The terminal carboxyl content of the purified glycolide was 9.1 μmol / g as measured by acid-base titration. The amounts of n-butanol and nonaethylene glycol dimethyl ether remaining in the glycolide as measured by liquid chromatography were 0.098%, and the amount of n-butanol remaining was 603 ppm.

[0062] Example 8 50 g of crude glycolide obtained in Example 1 was mixed with 25 g of n-butanol (water content 30 ppm or less) and 25 g of nonaethylene glycol dimethyl ether, and the solid-liquid mixture was stirred at room temperature for 1 hour. The stirring was stopped, and the mixture was suction filtered to obtain 41 g of filter cake. The filter cake was mixed with 82 g of n-butanol, and the mixture was heated to 80°C to form a homogeneous solution. With a rotation speed of 100 rpm, the solution was cooled to room temperature at a rate of 10°C / h, and the glycolide was separated from the system. The resulting mixture was suction filtered, and the filter cake was subjected to the above cooling, recrystallization, and filtration process once. The solid obtained by filtration was vacuum dried at 30°C for 8 hours, yielding 32.1 g of white crystals with a total yield of 64.2%. The purity of the purified glycolide measured by DSC was 99.50%. The terminal carboxyl content of the purified glycolide was measured by acid-base titration to be 6.2 μmol / g. The remaining amounts of n-butanol and nonaethylene glycol dimethyl ether in the glycolide were measured by liquid chromatography to be 0.079%, and the remaining amount of n-butanol was 596 ppm.

[0063] Furthermore, the present invention also provides the following group of technical solutions, specifically including technical solutions A1 to A8: A1. A method for purifying glycolide, comprising extracting impurities from crude glycolide with solvent A, followed by recrystallization with solvent B, wherein solvent A comprises at least two solvents, and the solvents are miscible with each other; The solvent A is preferably a mixed solvent of solvent I and solvent II, where solvent I is selected from polyalcohol ethers having a boiling point of 180°C or higher at atmospheric pressure, solvent I is preferably selected from at least one polyalkylene glycol ether, solvent II is selected from saturated alcohols having a boiling point of 120°C or lower at atmospheric pressure, and solvent II is preferably selected from at least one saturated monohydric alcohol; The solvent B is selected from saturated alcohols having a boiling point of 120° C. or less at atmospheric pressure, preferably from at least one saturated monohydric alcohol, and the solvent B is the same as or different from the solvent II.

[0064] A2. A method for purifying glycolide according to technical solution A1, characterized in that it comprises the following steps: (1) a step of mixing and stirring crude glycolide and solvent A, filtering the resulting solid-liquid mixture, and recovering the resulting filter cake; (2) mixing the filter cake obtained in step (1) with solvent B, heating the resulting mixture, and then cooling the resulting solution to separate glycolide crystals, and recovering the resulting filter cake by filtration; Preferably, after repeating step (2) at least once, the resulting filter cake is dried under vacuum.

[0065] A3. A method for purifying glycolide according to technical solution A1, comprising: In step (1), the mass ratio of crude glycolide to solvent A is (0.5-5):1, preferably (0.5-2):1; and / or in step (2), the mass ratio of filter cake to solvent B is (0.05-5):1, preferably (0.1-1):1.

[0066] A4. A method for purifying glycolide according to technical solution A1, comprising: The mass fraction of solvent II in solvent A is 50% or more but not 100%, and preferably the mass fraction of solvent II is 50 to 80%.

[0067] A5. A method for purifying glycolide according to technical solution A1, comprising: The solvent I is selected from at least one of polyalkylene glycol monoethers or polyalkylene glycol diethers, more preferably polyethylene glycol ethers, and even more preferably polyethylene glycol diethers; and / or the solvent II is selected from at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, and isobutyl alcohol; and / or the solvent B is selected from at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, and isobutyl alcohol.

[0068] A6. The method for purifying glycolide according to technical solution A5, characterized in that: The degree of polymerization of ethylene glycol in the polyethylene glycol diether is 20 or less, preferably 10 or less.

[0069] A7. A method for purifying glycolide according to technical solution A2, characterized in that: In step (1), the temperature for mixing is 0 to 40°C, preferably 0 to 20°C; and / or, in step (2), the temperature to which the resulting mixture is heated is 70 to 80°C, preferably 75 to 80°C; and the temperature to which the resulting solution is cooled is 0 to 25°C, preferably 15 to 25°C.

[0070] A8. A method for purifying glycolide according to technical solution A1 or A2, comprising: The crude glycolide is obtained by depolymerization of polyglycolic acid and / or polyglycol ester, and preferably has a glycolide purity of 75 wt% or more and less than 95 wt%.

[0071] A9. Purified glycolide obtained by treatment with any one of technical solutions A1 to A8.

[0072] Furthermore, the present invention also provides the following technical solutions, specifically including technical solutions B1 to B19: B1. A method for purifying glycolide, comprising the steps of: (1) a step of extracting impurities from crude glycolide into a solvent A to obtain a glycolide-containing phase and an impurity-containing phase (the glycolide-containing phase refers to a phase in which the glycolide content is higher than the glycolide content in the crude glycolide, the impurity-containing phase refers to a phase in which the impurity content is higher than the impurity content in the crude glycolide, and the impurities refer to a general term for substances other than glycolide in the crude glycolide); (2) Recrystallizing the glycolide-containing phase with solvent B, wherein solvent A comprises at least two solvents, and the solvents are miscible with each other.

[0073] B2. A method for purifying glycolide according to any of the preceding technical solutions, characterized in that the solvent A comprises solvent I and solvent II, solvent I is selected from polyalcohol ethers having a boiling point of 180°C or higher at atmospheric pressure, and solvent II is selected from saturated alcohols having a boiling point of 120°C or lower at atmospheric pressure.

[0074] B3. A method for purifying glycolide according to any of the above technical solutions, characterized in that in step (1), solvent I and solvent II are added simultaneously or sequentially.

[0075] B4. A method for purifying glycolide according to any of the preceding technical solutions, characterized in that step (2) is carried out directly after step (1), or that after step (1), the glycolide-containing phase is treated without changing the composition of the glycolide-containing phase, and then step (2) is carried out.

[0076] In the present invention, the treatment described in Technical Solution B4 is not particularly limited as long as the composition of the glycolide-containing phase is not changed, for example, the treatment includes heating, cooling, pressurization, decompression, standing and storage, etc.

[0077] B5. A method for purifying glycolide according to any of the above technical solutions, characterized in that solvent A is a mixed solvent of solvent I and solvent II, solvent I is selected from polyalcohol ethers having a boiling point of 180°C or higher at atmospheric pressure, and solvent II is selected from saturated alcohols having a boiling point of 120°C or lower at atmospheric pressure.

[0078] B6. The method for purifying glycolide according to any of the previous technical solutions, characterized in that the solvent B comprises a saturated alcohol having a boiling point of 120°C or less at atmospheric pressure, and the solvent B is the same as or different from solvent II.

[0079] B7. A method for purifying glycolide according to any of the preceding technical solutions, characterized in that solvent B is a saturated alcohol having a boiling point of 120°C or less at atmospheric pressure, and solvent B is the same as or different from solvent II.

[0080] B8. A method for purifying glycolide according to any of the preceding technical solutions, characterized in that solvent A is a mixed solvent of solvent I and solvent II, solvent I is at least one polyalkylene glycol ether having a boiling point of 180°C or higher at atmospheric pressure, solvent II is at least one saturated monohydric alcohol having a boiling point of 120°C or lower at atmospheric pressure, solvent B is at least one saturated monohydric alcohol having a boiling point of 120°C or lower at atmospheric pressure, and solvent B is the same as or different from solvent II.

[0081] B9. A method for purifying glycolide according to any of the previous technical solutions, characterized in that the method comprises the following steps: (1) a step of mixing and stirring crude glycolide and solvent A, filtering the resulting solid-liquid mixture, and recovering the resulting filter cake; (2) mixing the filter cake obtained in step (1) with solvent B, heating the resulting mixture, and then cooling the resulting solution to separate glycolide crystals, and recovering the resulting filter cake by filtration; After repeating step (2) at least once, the resulting filter cake is preferably vacuum-dried.

[0082] B10. A method for purifying glycolide according to any of the aforementioned technical solutions, comprising: In step (1), the mass ratio of crude glycolide to solvent A is (0.5-5):1, for example, (0.5-2):1; and / or, in step (2), the mass ratio of filter cake to solvent B is (0.05-5):1, for example, (0.1-1):1.

[0083] B11. A method for purifying glycolide according to any of the aforementioned technical solutions, comprising: The mass fraction of solvent II in solvent A is 50% or more but not equal to 100%, for example, the mass fraction of solvent II is 50-99%, or 50-80%, for example, 50%, 60%, 70%, 80%, or 90%.

[0084] B12. A method for purifying glycolide according to any of the aforementioned technical solutions, comprising: The solvent I is selected from at least one polyalkylene glycol monoether or polyalkylene glycol diether, such as polyethylene glycol ether, such as polyethylene glycol diether; and / or the solvent II is selected from at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, isobutanol, sec-butyl alcohol, 2-pentanol, 3-pentanol, 2-methyl-2-butanol, 3-methyl-2-butanol; and / or the solvent B is at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, isobutanol, sec-butyl alcohol, 2-pentanol, 3-pentanol, 2-methyl-2-butanol, 3-methyl-2-butanol.

[0085] B13. A method for purifying glycolide according to technical solution B12, comprising: The degree of polymerization of ethylene glycol in the polyethylene glycol diether is 20 or less, for example, 10 or less.

[0086] B14. A method for purifying glycolide according to technical solution B9, comprising: In step (1), the temperature for mixing is 0 to 40°C, for example, 0 to 20°C; and / or, in step (2), the temperature to which the resulting mixture is heated is 70 to 80°C, for example, 75 to 80°C; and the temperature to which the resulting solution is cooled is 0 to 25°C, for example, 15 to 25°C.

[0087] B15. A method for purifying glycolide according to any of the aforementioned technical solutions, comprising: Crude glycolide is obtained by depolymerization of polyglycolic acid and / or polyglycol ester, and has a glycolide purity of, for example, 75 wt% or more and less than 95 wt%.

[0088] B16. A process for purifying glycolide according to any of the aforementioned technical solutions, wherein said crude glycolide is in a solid or molten state, preferably said crude glycolide has a terminal carboxyl content of more than 10 μmol / g, preferably more than 100 μmol / g, more preferably more than 500 μmol / g.

[0089] B17. A purified glycolide obtained by a method according to any one of Technical Solutions B1 to B16, preferably comprising (A) a polyalcohol ether having a boiling point at atmospheric pressure of 180°C or higher, such as a polyalkylene glycol ether having a boiling point at atmospheric pressure of 180°C or higher, and (b) a saturated alcohol having a boiling point at atmospheric pressure of 120°C or lower, such as a saturated monohydric alcohol having a boiling point at atmospheric pressure of 120°C or lower, wherein the contents of components (A) and (b) are equal to or greater than zero, preferably both are greater than zero, and the total content of components (A) and (b) is 800 ppm or lower, based on the total weight of the purified glycolide; Preferably, the content of component (A) is 500 ppm or less, preferably the content of component (A) is greater than zero and less than 300 ppm, and the content of component (b) is greater than 0 and less than 600 ppm, more preferably the content of component (A) is greater than 5 ppm and less than 200 ppm, and the content of component (b) is greater than 100 ppm and less than 600 ppm, and even more preferably the content of component (A) is greater than 5 ppm and less than 30 ppm, and the content of component (b) is greater than 125 ppm and less than 350 ppm; and / or the terminal carboxyl content of the purified glycolide is 1 to 10 μmol / g, preferably 2 to 5 μmol / g.

[0090] B18. A glycolide-containing composition comprising glycolide, The glycolide-containing composition contains glycolide, (a) a polyalcohol ether having a boiling point of 180°C or higher at atmospheric pressure, such as a polyalkylene glycol ether having a boiling point of 180°C or higher at atmospheric pressure, and (b) a saturated alcohol having a boiling point of 120°C or lower at atmospheric pressure, such as a saturated monohydric alcohol having a boiling point of 120°C or lower at atmospheric pressure, wherein the contents of components (a) and (b) are zero or higher, preferably both are greater than zero, based on the total weight of the glycolide-containing composition, and the total content of components (a) and (b) is 800 ppm or lower, preferably 500 ppm or lower, and preferably the content of component (a) is is greater than zero and less than 300 ppm, the content of component (b) is greater than zero and less than 600 ppm, more preferably the content of component (a) is greater than 5 ppm and less than 200 ppm, the content of component (b) is greater than 100 ppm and less than 600 ppm, and even more preferably the content of component (a) is greater than 5 ppm and less than 30 ppm, and the content of component (b) is greater than 125 ppm and less than 350 ppm; and / or in the glycolide-containing composition, the terminal carboxyl content is 1 to 10 μmol / g, preferably 2 to 5 μmol / g.

[0091] B19. Complex solvents are: The composite solvent is characterized in that it comprises (a) a polyalcohol ether having a boiling point of 180°C or higher at atmospheric pressure, such as a polyalkylene glycol ether having a boiling point of 180°C or higher at atmospheric pressure, and (b) a saturated alcohol having a boiling point of 120°C or lower at atmospheric pressure, such as a saturated monohydric alcohol having a boiling point of 120°C or lower at atmospheric pressure, and the weight ratio of component (a) to component (b) is 50:50 to 1:99.

[0092] In the present invention, unless otherwise specified, room temperature means 15 to 20°C.

[0093] In this disclosure, percentages are by weight unless otherwise indicated.

Claims

1. (1) extracting impurities from crude glycolide using solvent A to obtain a glycolide-containing phase and an impurity-containing phase; (2) recrystallizing the glycolide-containing phase using solvent B; Solvent A comprises at least two solvents, and the solvents are miscible with each other; A method for purifying glycolide, wherein the solvent A comprises solvent I and solvent II, solvent I is selected from polyalcohol ethers having a boiling point of 180°C or higher at atmospheric pressure, and solvent II is selected from saturated alcohols having a boiling point of 120°C or lower at atmospheric pressure.

2. 2. The method for purifying glycolide according to claim 1, wherein in step (1), solvent I and solvent II are added simultaneously or successively.

3. 3. The method for purifying glycolide according to claim 2, wherein step (2) is carried out immediately after step (1), or after step (1), the glycolide-containing phase is treated without changing the composition of the glycolide-containing phase, and then step (2) is carried out.

4. 4. The method for purifying glycolide according to claim 3, wherein pre-solvent A is a mixed solvent of solvent I and solvent II, solvent I is selected from polyalcohol ethers having a boiling point of 180° C. or higher at atmospheric pressure, and solvent II is selected from saturated alcohols having a boiling point of 120° C. or lower at atmospheric pressure.

5. 4. The method for purifying glycolide according to claim 3, wherein the solvent B comprises a saturated alcohol having a boiling point of 120° C. or less at atmospheric pressure, and the solvent B is the same as or different from the solvent II.

6. 4. The method for purifying glycolide according to claim 3, wherein the solvent B is a saturated alcohol having a boiling point of 120° C. or less under atmospheric pressure, and the solvent B is the same as or different from the solvent II.

7. 4. The method for purifying glycolide according to claim 3, wherein the solvent A is a mixed solvent of solvent I and solvent II, solvent I is at least one polyalkylene glycol ether having a boiling point of 180° C. or higher at atmospheric pressure, solvent II is at least one saturated monohydric alcohol having a boiling point of 120° C. or lower at atmospheric pressure, solvent B is at least one saturated monohydric alcohol having a boiling point of 120° C. or lower at atmospheric pressure, and solvent B is the same as or different from solvent II.

8. (1) mixing and stirring crude glycolide and solvent A, filtering the resulting solid-liquid mixture, and recovering the resulting filter cake; (2) mixing the filter cake obtained in step (1) with solvent B, heating the resulting mixture, and then cooling the resulting solution to separate glycolide crystals, and recovering the resulting filter cake by filtration.

9. A method for purifying glycolide as described in claim 8, characterized in that it comprises a step of repeating step (2) at least once and then vacuum-drying the obtained filter cake.

10. In step (1), the mass ratio of the crude glycolide to solvent A is (0.5-5) to 1; and / or 4. The method for purifying glycolide according to claim 3, wherein in step (2), the mass ratio of the filter cake obtained in step (1) to solvent B is (0.05-5) to 1.

11. 4. The method for purifying glycolide according to claim 3, wherein the mass fraction of solvent II in solvent A is greater than or equal to 50% but not equal to 100%.

12. The method for purifying glycolide according to claim 11, wherein the mass fraction of solvent II in solvent A is 50 to 80%.

13. said solvent I is selected from at least one polyalkylene glycol monoether or polyalkylene glycol diether, and / or said solvent II being selected from at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, iso-butanol, sec-butyl alcohol, 2-pentanol, 3-pentanol, 2-methyl-2-butanol, 3-methyl-2-butanol; and / or 4. The method for purifying glycolide according to claim 3, wherein solvent B is selected from at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, iso-butanol, sec-butyl alcohol, 2-pentanol, 3-pentanol, 2-methyl-2-butanol, and 3-methyl-2-butanol.

14. The method for purifying glycolide according to claim 13, wherein said solvent I is a polyethylene glycol diether.

15. 15. The method for purifying glycolide according to claim 14, wherein the degree of polymerization of ethylene glycol in the polyethylene glycol diether is 20 or less.

16. In step (1), the temperature for mixing is 0 to 40°C, and / or 9. The method for purifying glycolide according to claim 8, wherein in step (2), the temperature to which the obtained mixture is heated is 70 to 80°C, and the temperature to which the obtained solution is cooled is 0 to 25°C.

17. 4. The method for purifying glycolide according to claim 3, wherein the crude glycolide is obtained by depolymerization of polyglycolic acid and / or polyglycol ester.

18. 4. The method for purifying glycolide according to claim 3, wherein the crude glycolide is in a solid or molten state, and the crude glycolide has a terminal carboxyl content of greater than 10 μmol / g.