Method for purifying crystalline substances

Abstract

The present invention provides a phase transition-diffusion coupled crystallization method for purifying a crystalline substance, the method comprising the following steps: (1) adding a crude crystalline substance in a molten state to a solid-liquid mixture I in a solution equilibrium state to obtain a solid-liquid mixture II; wherein the solid phase contains the crystalline substance in a solid state and may contain impurities, and the solution phase contains a solvent and the crystalline substance in a molten state and may contain impurities; and (2) separating the solid-liquid mixture II into solid and liquid phases.

Description

Detailed Description of the Invention

[0001] [Technical Field] The present invention relates to a method for purifying crystalline materials (such as glycolide).

[0002] [Background technology] Ring-opening polymerization is an important chemical reaction process, and its application value has been comprehensively explored in many fields. With the development of industrial catalysts and polymerization technology, the scope of applications of ring-opening polymerization is constantly expanding, allowing more types of cyclic monomers to be used in the synthesis of polymeric materials. Ring-opening polymerization is a key step in the synthesis of polymeric materials. For example, the preparation of biodegradable polymers such as polyglycolic acid (PGA), polylactic acid (PLA), and polycaprolactone (PCL) all rely on ring-opening polymerization. These polymeric materials have a wide range of applications in the fields of medicine, packaging, and biomedicine, and also have a positive impact on environmental protection. These polymers can be used to synthesize important compounds in the biomedical field, such as drug carriers, biosensors, and drug molecules. These applications contribute to improving drug delivery and therapeutic effects.

[0003] Cyclic monomers are typically used as raw materials for ring-opening polymerization reactions. These cyclic monomers typically have reactive groups, such as esters, ethers, and ketones, that readily open the ring. Under certain conditions and with the aid of a catalyst, the corresponding linear polymers can be prepared. However, these cyclic monomers typically contain trace amounts of impurities derived from upstream monomer synthesis units. These impurities may originate from the synthesis, separation, and purification processes of the raw materials, as well as unfavorable storage conditions. Common trace impurities that may be present in cyclic monomers include unreacted starting materials (incompletely reacted starting monomers or reaction intermediates may remain during the synthesis of cyclic monomers), by-products (by-products may be generated during the synthesis of cyclic monomers, but are usually unwanted), catalyst residues, solvent residues (solvents are often used to aid in the synthesis or isolation of cyclic monomers; if the solvents are not completely removed, they may become a source of impurities), oxidation products (cyclic monomers may be oxidized by oxygen, resulting in oxidation products), and accidental ring-opening (small cyclic monomer molecules may be affected by, for example, water, resulting in ring-opening products, e.g., hydrolysates).

[0004] Removal of these impurities is very important because they can adversely affect the efficiency of the ring-opening polymerization reaction and the quality of the product. Reducing the presence of these impurities through necessary purification and separation processes can ensure product quality, improve reaction efficiency, meet environmental protection requirements, and ensure application safety. In practical production, purification of ring-opening polymerization monomers is crucial to successfully achieving the target applications of the material.

[0005] Take the purification of glycolide, the polymerization monomer for polyglycolic acid (PGA), for example. Industrially produced glycolide typically contains various impurities, such as water, glycolic acid, and glycolic acid oligomers, and is called crude glycolide. The trace amounts of active hydrogen contained in these impurities can significantly affect the molecular weight of the polymer during ring-opening polymerization of glycolide. Therefore, crude glycolide obtained in an upstream unit (such as a depolymerization ring-opening unit) must be purified by recrystallization or washing, a process generally referred to as purification.

[0006] Reported methods for purifying glycolide include multiple recrystallizations using various organic solvents. For example, in Example 3 of U.S. Patent No. US4727163A, crude glycolide obtained by depolymerization of glycolic acid oligomers is purified using ethyl acetate. This crude glycolide can only be purified to a purity of 90% and a yield of 59.4% after two recrystallizations. Obtaining glycolide of higher purity requires more recrystallizations, which increases the amount of solvent used and the disposal of large amounts of waste solvent and various impurities contained in the crude glycolide. Furthermore, the recrystallization process is usually complicated. Therefore, many researchers are exploring new methods for purifying glycolide.

[0007] Prior art also includes glycolide purification schemes involving multiple alcohol washes. Chinese Invention Patent CN107868075A discloses a glycolide purification method that uses a cooling recrystallization, mixing, and washing with a poor solvent, followed by filtration and drying to purify crude glycolide. This method uses alcohols as the washing solvent. Because glycolide's solubility in alcohol is significantly lower than its solubility in good solvents such as ethyl acetate, the single-pass purification yield is improved. However, the amount of solvent used in the purification process remains large, and solvent recycling is difficult.

[0008] Japanese Patent Application Publication No. JP1984148777A discloses a method for purifying crude glycolide, which involves immersing a crude glycolide melt in ethyl acetate at a lower temperature, thereby avoiding thermal degradation of the crude glycolide and enabling the production of high-purity glycolide in a higher yield. Crude glycolide is heated and melted at a relatively low temperature, and then added dropwise to an organic solvent with stirring. The resulting glycolide suspension is cooled to a predetermined temperature, and the precipitate is then separated and dried. However, this method involves competition between dissolution of the melt in the organic solvent and crystallization upon cooling, resulting in uncertainty about the location and time of crystal precipitation, resulting in non-uniform particle sizes of the precipitated crystals and reduced extraction efficiency.

[0009] Summary of the Invention To solve the technical problems existing in the prior art, the present invention provides a method for purifying crystalline substances, in particular a method that can be used to purify glycolide.

[0010] The present invention provides a phase change-diffusion coupled crystallization method for purifying a crystalline material, the method comprising the steps of: (1) adding a crude crystalline material in a molten state to a solid-liquid mixture I in a solution equilibrium state to obtain a solid-liquid mixture II; wherein the solid-liquid mixtures I and II each contain a solid phase and a solution phase, the solid phase containing the crystalline material in a solid state and possibly containing impurities, and the solution phase containing a solvent and the crystalline material in a dissolved state and possibly containing impurities; and (2) A step of subjecting the solid-liquid mixture II to solid-liquid separation.

[0011] In the present invention, preferably, the molten coarse crystalline material has a temperature higher than the temperature of the solid-liquid mixture I, and such temperature difference is sufficient to cause a phase transition in the molten coarse crystalline material and complete the phase transition.

[0012] In the present invention, preferably, the crystalline substance in the solid phase of the solid-liquid mixture I has a higher purity than the purity of the crude crystalline substance in the molten state, and such a difference in purity is sufficient to allow an effective amount of an impurity in the crude crystalline substance in the molten state to diffuse into the solvent.

[0013] In the present invention, the device containing the solid-liquid mixture I in step (1) preferably comprises a heat exchange device for removing the heat caused by the addition of the coarse crystalline material in a molten state, such as a jacket or coil in which a cooling medium, for example water, is used.

[0014] A typical example of a crystalline substance described in the present invention is glycolide. In this case, according to the present invention, a crude glycolide melt is added to a solid-liquid mixture I at a constant rate, thereby simultaneously carrying out the cooling crystallization process and the extraction process. That is, the crude glycolide melt precipitates rapidly and uniformly as solid particles, while impurities are extracted into the liquid phase, producing purified glycolide crystals that can be recovered through a solid-liquid separation process.

[0015] When the crystalline substance is glycolide, the present invention solves some of the problems existing in the prior art by adding a certain amount of solid crystalline particles to a pure organic solvent and then using this solid-liquid mixture to melt glycolide. Compared with the conventional recrystallization process, the present invention allows for a constant process temperature and eliminates the need for a cooling process over a large temperature span. It has the advantages of simple operation, ease of industrial scale-up, and low energy consumption.

[0016] In the prior art, the problem of high acid content is solved by increasing the amount of organic solvent used and the number of purification stages, but this results in problems such as high solvent consumption, long purification processes, and complicated operations. In addition, purification schemes that do not use organic solvents, such as melt crystallization and distillation, also solve the problem of high impurity content by increasing the purification, but this also results in problems such as long purification processes and complicated operations. The present invention not only solves the technical problem of high acid content in crystalline substances (such as glycolide), but also solves the problem of uneven particle sizes of crystals precipitated in the crystallization process. Therefore, the present invention provides a simple and efficient method for purifying crystalline substances (such as glycolide), and the purified crystalline substances (such as glycolide) have uniform particle sizes and low impurity contents.

[0017] Detailed Description of the Invention In the present invention, the term "crude crystalline material" refers to a material to be purified by the method of the present invention, which has a relatively low purity that needs to be improved by the method of the present invention. For example, the crude crystalline material has a purity of about 90% or less. Therefore, an example of the "purified" concentration in the present invention may refer to a purity of about 90% or less.

[0018] In the present invention, solid-liquid mixture I and solid-liquid mixture II are solid-liquid mixtures containing a solid-state crystalline substance and a solution of the crystalline substance, respectively, before and after the addition of the crude crystalline substance in step (1) of the method of the present invention, and each has a relatively stable composition. In contrast, a solid-liquid mixture also exists during the conversion from solid-liquid mixture I to solid-liquid mixture II, and it should be understood that this solid-liquid mixture may be referred to as an "intermediate solid-liquid mixture" in the present invention. As step (1) progresses, the composition of the intermediate solid-liquid mixture gradually changes from solid-liquid mixture I to solid-liquid mixture II.

[0019] In the present invention, the preparation of the solid-liquid mixture I is not particularly limited as long as the crystalline substance can reach a dissolution equilibrium state. For example, the solid-liquid mixture I described in the present invention can be obtained by adding a solid or molten crystalline substance of a specific purity to a solvent and mixing them thoroughly until a dissolution equilibrium state is reached.

[0020] The present invention can be considered to involve three distinct phases: a melt phase (crude crystalline material in a molten state), a solution phase, and a solid phase. It should be understood that each phase contains not only purified or to be purified crystalline material, but also substantial impurities. In other words, the melt phase in the present invention contains crystalline material in a molten state and may contain impurities; the solid phase contains crystalline material in a solid state and may contain impurities; and the liquid phase contains solvent and crystalline material in a dissolved state and may contain impurities. It should be understood that, preferably, the "crystalline material" referred to in the three distinct phases of the present invention is considered to be the same chemical substance.

[0021] Unlike conventional melt crystallization or solution crystallization, the present invention utilizes the phase transition-diffusion coupling effect of the three states of a crystalline substance (molten, dissolved, and solid) under specific conditions during the crystallization process by adding a molten crystalline substance to a supersaturated solid-liquid mixture I of a crystalline substance. Here, one or both of the molten crystalline substance and the solution of the crystalline substance can be the crystalline substance of the purity to be purified, and when the crystalline substance is in the solid state, it has a higher purity.

[0022] Melt crystallization removes impurities without the addition of solvents through the solid-liquid equilibrium of melting and crystallization of the substance being separated. This is achieved by gradually lowering the temperature of the initial liquid state to achieve partial crystallization based on the difference in the freezing points of the substances being separated.

[0023] The present invention is completely different. The present invention involves the addition of a molten coarse crystalline material to a solid-liquid mixture I of a supersaturated crystalline material and the phase transition of the molten coarse crystalline material, without the gradual temperature decrease of the molten coarse crystalline material during the process. In contrast, in the specific phase-transition-diffusion-coupled crystallization method of the present invention, the molten coarse crystalline material is added to the solid-liquid mixture I in a controlled manner and rate, and the temperature of the solid-liquid mixture remains unchanged or substantially unchanged during the process, so that the molten coarse crystalline material completes a microscopic phase transition within a few seconds.

[0024] On the other hand, solution crystallization allows the purification of solid substances by utilizing the temperature-dependent solubility of the substance. This method is primarily used for substances whose solubility decreases significantly with decreasing temperature. Generally, the substance to be purified is dissolved in a good solvent. The conventional solution crystallization procedure involves lowering the temperature of a relatively high-temperature saturated solution to create a supersaturated state, resulting in the precipitation of crystals.

[0025] The present invention is completely different: although according to the present invention a solution of the crystalline substance to be purified is used, in fact the present invention utilizes a solid-liquid mixture I in solution equilibrium between a saturated solution of the crystalline substance and its undissolved solid.

[0026] Furthermore, unlike conventional solution crystallization, which generally uses a good solvent for the crystalline substance to be purified, the present invention does not have such a requirement. In some embodiments, it is preferable to use a poor solvent for the crystalline substance to be purified; and / or it is preferable that the solvent used is a good solvent for the impurities contained in the crystalline substance to be purified. For the purposes of the present invention only, the terms "good solvent" and "poor solvent" have meanings consistent with the general understanding in the art. According to a preferred embodiment of the present invention, the solvent used is a poor solvent for the crystalline substance to be purified, for example, the solubility of the crystalline substance to be purified per 100 g of solvent is 10 g or less; on the other hand, it is also preferable that the solubility of the crystalline substance to be purified per 100 g of solvent is 0.1 g or more, preferably 0.2 g or more. Thus, according to a preferred embodiment of the present invention, the solvent used is a good solvent for the impurities contained in the crystalline substance to be purified, and is also a poor solvent for the crystalline substance to be purified.

[0027] Furthermore, unlike the temperature drop during solution crystallization, the temperature of solid-liquid mixture I does not change or remains substantially unchanged during the process of the present invention.

[0028] Unlike solution crystallization methods that primarily utilize the precipitation and crystallization of a substance to be purified from a solution, the specific phase change-diffusion coupled crystallization method of the present invention allows the substance to be purified during step (1) because impurities in the system diffuse into solid-liquid mixture I and then into an intermediate solid-liquid mixture. In particular, in the phase change-diffusion coupled crystallization method of the present invention, the phase change of the crude crystalline substance in the molten state and the diffusion of impurities occur simultaneously or substantially simultaneously. In other words, for example, the diffusion of impurities occurs simultaneously throughout most (e.g., more than half) of the phase change process until diffusion equilibrium is reached in the system and the impurity concentration in the solution no longer changes, thereby obtaining solid-liquid mixture II.

[0029] In the phase transition-diffusion coupled crystallization method of the present invention, for the phase transition of the molten crude crystalline material, it is preferable that there is a sufficient temperature difference between the molten crude crystalline material and the solid-liquid mixture I to provide sufficient driving force for the phase transition, for example, the temperature difference is 15°C or more, preferably 25°C or more. At the same time, the method of the present invention is not a separate phase transition process but a phase transition-diffusion coupled process. Therefore, taking into account the diffusion process (especially the diffusion of impurities) and the dissolution of impurities in the solvent, it is preferable that the temperature difference is 85°C or less, preferably 75°C or less.

[0030] In the phase transition-diffusion coupled crystallization method of the present invention, the driving force for the phase transition of the molten crude crystalline material is a temperature difference; or, more precisely, solid-liquid mixture I provides sufficient cooling capacity for the molten crude crystalline material. At the same time, without control, the addition of the molten crude crystalline material to solid-liquid mixture I will cause the temperature of the intermediate solid-liquid mixture obtained in the system to gradually increase. Therefore, to continuously provide sufficient driving force for the phase transition, it is preferable to control the temperature of the system (especially the intermediate solid-liquid mixture) so that the temperature during the conversion from solid-liquid mixture I to solid-liquid mixture II does not change or does not change substantially, with the change being 15°C or less, preferably 10°C or less. For example, the apparatus containing solid-liquid mixture I in step (1) is equipped with a heat exchanger, such as a jacket or coil using a cooling medium such as water, to remove the heat generated by the addition of the molten crude crystalline material.

[0031] It is readily apparent that for a given crude crystalline material to be purified, the temperature of the molten crude crystalline material can be increased or the temperature of solid-liquid mixture I can be decreased by achieving a sufficient temperature difference between it and the solid-liquid mixture. However, the method of the present invention is similarly not a separate phase transition process but a combined phase transition-diffusion process. Therefore, taking into account the diffusion process (especially the diffusion of impurities) and the dissolution of impurities into the solvent, it is preferable that the temperature of solid-liquid mixture I, the intermediate solid-liquid mixture, and / or solid-liquid mixture II is not too low, for example, 4°C or higher.

[0032] As described above, in the phase change-diffusion coupled crystallization method of the present invention, the driving force for the phase transition of the molten coarse crystalline material is a temperature difference. Therefore, it is preferable to gradually and controllably add the molten coarse crystalline material to solid-liquid mixture I all at once or continuously so that the added molten coarse crystalline material receives sufficient driving force for the phase transition. Therefore, it is preferable to add solid-liquid mixture I to solid-liquid mixture II by a method selected from at least one of dropwise addition, injection, spraying, scattering, and atomization.

[0033] As an example, a molten coarse crystalline material is added to solid-liquid mixture I at a constant rate. As the molten coarse crystalline material changes to a solid, the content of the suspended solid phase in the intermediate solid-liquid mixture gradually increases with the addition of the molten coarse crystalline material. For purposes of the present invention, this process can be referred to as Feeding Process 1. In this Process 1, no raw materials are removed from the system, and no raw materials other than the molten coarse crystalline material are added to the system. Meanwhile, the amount of the intermediate solid-liquid mixture gradually increases.

[0034] Alternatively, after the completion of Supply Process 1 (e.g., after diffusion equilibrium is reached in the system), the molten crude crystalline material can be added to the dynamically formed solid-liquid mixture at a constant rate to stabilize the content of the suspended solid phase in Solid-Liquid Mixture II and achieve continuous operation. For purposes of the present invention, this process can be referred to as Supply Process 2. In Supply Process 2, while adding the molten crude crystalline material, a solvent that is the same as that used in the solid-liquid mixture and has the same temperature as the solid-liquid mixture is added to Solid-Liquid Mixture II. The addition of the solvent stabilizes the content of the suspended solid phase in Solid-Liquid Mixture II. At the same time, the solid-liquid mixture is discharged from the apparatus at a constant rate. The discharge flow rate is equal to the sum of the flow rates of the molten crude crystalline material and the solvent, allowing the amount of material in the apparatus to be (substantially) constant.

[0035] The phase-transition-diffusion-coupled crystallization method of the present invention involves coupling a phase transition process with a diffusion process and utilizes three states of the crystalline material to be purified: molten, dissolved, and solid. Without being bound by any known theory, it is believed that state transformations occur among the three states of the crystalline material to be purified during the implementation of the method of the present invention. However, from a macroscopic perspective of the process and results of the method of the present invention, it is generally essentially equivalent to adding a crude crystalline material in a molten state to solid-liquid mixture I and undergoing a phase transition to form a crystalline material in a solid-liquid mixture II with improved purity. Therefore, the content of the solid phase in solid-liquid mixture I (and preferably even solid-liquid mixture II) of the present invention must be appropriately controlled for the purposes of the present invention. Therefore, the weight content of the solid phase in solid-liquid mixture I is 0.5% to 25%, preferably 2% to 25%; and / or the weight content of the solid phase in solid-liquid mixture II is 50% or less, preferably 40% or less.

[0036] Preferably, in the phase change-diffusion coupled crystallization method of the present invention, the solid phase in solid-liquid mixture I and / or solid-liquid mixture II also exhibits desirable homogeneity to facilitate the phase change process and the diffusion process.

[0037] On the other hand, the solid phase particles are uniformly distributed in solid-liquid mixture I and / or solid-liquid mixture II. For example, when two different samples of the solid-liquid mixture are taken from any two different positions in solid-liquid mixture I and the D50 particle size is measured, the deviation in D50 particle size between the two different samples of the solid-liquid mixture is 30% or less, preferably 20% or less; and / or when two different samples of the solid-liquid mixture are taken from any two different positions in solid-liquid mixture II to measure the D50 particle size, the deviation in D50 particle size between the two different samples of the solid-liquid mixture is 30% or less, preferably 20% or less. Thus, for example, solid-liquid mixture I and / or solid-liquid mixture II may be a suspension.

[0038] On the other hand, the size of the individual particles of the solid phase distributed in solid-liquid mixture I and / or solid-liquid mixture II is relatively uniform. For example, in the solid phase of solid-liquid mixture I and / or solid-liquid mixture II, the ratio of D90 to D10 of the solid phase is 10 or less, preferably 7 or less, and more preferably 5 or less.

[0039] As described above, in the phase change-diffusion coupled crystallization method of the present invention, from a macroscopic observation of the process and results of the method of the present invention, it can be generally seen that, on the one hand, the method of the present invention is essentially equivalent to a molten coarse crystalline material added to solid-liquid mixture I undergoing a phase transition to form a crystalline material in a solid state with improved purity in solid-liquid mixture II. On the other hand, the method of the present invention is essentially equivalent to an impurity in the molten coarse crystalline material added to solid-liquid mixture I diffusing into the solution phase of solid-liquid mixture II. For purposes of the present invention, the primary driving force for phase transition may be temperature difference, and the primary driving force for diffusion may be purity difference. However, without being bound by any known theory, those skilled in the art should understand that the process actually involved in the present invention is much more complex than the macroscopic observation, and therefore can and should be described as a phase change-diffusion coupled process, since the present invention utilizes the phase change-diffusion coupled effect of the three states of a crystalline material (molten, dissolved, and solid) under specific conditions during the crystallization process.

[0040] Therefore, for the purposes of the present invention, in one embodiment, it is preferable that the purity of the crystalline substance in the solid phase of solid-liquid mixture I is higher than the purity of the crude crystalline substance in the molten state, and that the purity difference is sufficient to allow an effective amount of impurities in the crude crystalline substance in the molten state to diffuse into the solvent. For example, the purity of the crude crystalline substance in the molten state is about 90% or less, for example, 85-90%, and the purity of the crystalline substance in the solid phase of solid-liquid mixture I is 95% or more, preferably 99% or more, for example, 99.5% or more. In this case, the purity difference between the crude crystalline substance in the molten state and the solid phase of solid-liquid mixture I (i.e., the difference in impurity content) can serve as an additional driving force for the purification of the crude crystalline substance in the molten state. At the same time, for the purposes of the present invention, although one or both of the crude crystalline substance in the molten state and the solution of the crystalline substance may contain the crystalline substance of the purity to be purified, in some cases, it is preferable that the solution of the crystalline substance contains the crystalline substance of a higher purity. For example, the purity of the crystalline substance in the solution of the crystalline substance is 90% or more, 95% or more, and preferably 99% or more.

[0041] It should be understood that the subject of the present invention is primarily a crystalline substance, and therefore, in some embodiments, phase transition can serve as the primary driving force behind the method of the present invention. Thus, in some cases, for example, when a crystalline substance with very high purity is desired, the method may be carried out starting from a crude crystalline substance that already has a relatively high purity, with phase transition as the primary driving force. Thus, for example, in some embodiments, the purity of the crude crystalline substance in the molten state is about 90% or more, e.g., 90-99%.

[0042] Thus, the method of the present invention can process crude crystalline materials with a wide range of purity, for example, the purity of the crude crystalline material in the molten state (e.g., per glycolide mass) may be 85% to 99%.

[0043] Therefore, due to the dual driving forces, i.e., temperature difference and phase transition, a crude crystalline material with low purity can be subjected to multiple purification steps by repeating the method of the present invention until the desired purity is achieved. For example, a crude crystalline material with a purity of 85-90% can be purified to a crystalline material with a purity of up to 99% or higher. It should be understood by those skilled in the art that, if necessary, multiple purification steps can be performed, for example, two, three, four, or five times, until the desired purity is achieved. In this case, the purity of the crystalline material in the solid phase of solid-liquid mixture I can be the same or different for each purification step. Preferably, the purity of the crystalline material in the solid phase of solid-liquid mixture I before the final purification step is higher than the purity of the crude crystalline material in the molten state.

[0044] When the purification method of the present invention is repeatedly carried out, the purified crystalline material obtained from the previous process run is melted to serve as a crude crystalline material in a molten state for the next process run. For example, the method of the present invention can typically be carried out in the form of a two-stage purification, in which the purified crystalline material obtained from the first process run is melted to serve as a crude crystalline material in a molten state for the second process run, and preferably the purity of the crystalline material in the solid phase of solid-liquid mixture I used for the second purification run is still higher than the purity in the crude crystalline material in a molten state for the second purification run.

[0045] The purification method of the present invention is widely applicable to various specific crystalline substances. In particular, from the above-mentioned features of the present invention, it can be understood that the purification method of the present invention is particularly suitable for crystalline substances that are distilled in the gas phase during the synthesis process, have a good solvent for the main impurities in the substance, and the resulting crystalline substance is solid at room temperature. For example, the crystalline substance is preferably a cyclic monomer having a melting point higher than -20°C, preferably selected from lactones (e.g., caprolactone, glycolide, lactide, 1,4-dioxane-2-one), cyclic formals (e.g., trioxane), and lactams (e.g., caprolactam), and is preferably a lactide compound such as glycolide or lactide.

[0046] In one embodiment, an object of the present invention is to provide a method for purifying glycolide, comprising the steps of: (1) adding molten crude glycolide to a solid-liquid mixture I to obtain a solid-liquid mixture II; wherein the solid-liquid mixture I contains glycolide crystals and a glycolide solution; (2) subjecting the solid-liquid mixture II to solid-liquid separation and recovering the solid phase to obtain purified glycolide; Optionally, (3) drying the solid phase recovered in step (2).

[0047] In a preferred embodiment of the present invention, in step (1): The addition technique is selected from at least one of dropwise addition, injection, spraying, scattering, and atomization; and / or The crude molten glycolide is unpurified crude molten glycolide and / or purified crude molten glycolide; and / or The weight content of glycolide in the molten crude glycolide is 85% to 99%.

[0048] In a preferred embodiment of the present invention, the molten crude glycolide is obtained by decomposition and ring-forming reaction of glycolic acid oligomers, preferably by condensing the gaseous products produced from the decomposition and ring-forming reaction of glycolic acid oligomers or by deep condensing the gaseous products to obtain solid crude glycolide, which is then heated to melt; The purified crude glycolide in a molten state is a melt containing a glycolide phase obtained by purifying crude glycolide obtained by decomposition and ring-forming reaction of glycolic acid oligomers by a conventional method. It is preferable that the crude glycolide is purified by a conventional method, then treated to a molten state, and further purified by the method of the present invention. If the substance containing the glycolide phase after purification by a conventional method is in a gaseous phase, the gaseous phase is condensed to a molten state. If the substance containing the glycolide phase after purification by a conventional method is in a solid phase, it is heated to a molten state.

[0049] The above-mentioned conventional purification method is a conventional method for purifying crude glycolide obtained by the decomposition and ring-forming reaction of glycolic acid oligomers in the prior art, and includes steps of extracting, washing, crystallizing, and distilling the unpurified crude glycolide.

[0050] In a preferred embodiment of the present invention, the temperature of the molten crude glycolide is between 75°C and 120°C; preferably between 80°C and 95°C; and / or The temperature of the molten purified crude glycolide is 80°C to 120°C, preferably 85°C to 95°C.

[0051] In the present invention, unpurified crude glycolide has a lower melting point. When a mixture of molten unpurified crude glycolide and molten purified crude glycolide is used, the melting point increases, and the temperature range required to maintain the molten state also increases accordingly, to match that of molten purified crude glycolide. Therefore, for the purposes of the present invention, taking into account factors such as differences in crystalline substances and differences in purity between crude crystalline substances, the temperature of the molten crude crystalline substance that can be used in the present invention needs only to be a temperature sufficient to bring the crude crystalline substance into a molten state. This temperature is generally near the melting point of the corresponding crystalline substance, but does not necessarily have to be higher than the melting point of the crystalline substance.

[0052] Thus, in a preferred embodiment of the present invention, the temperature of the molten crude crystalline material is at least the melting point of the crystalline material; preferably, the temperature of the molten crude crystalline material is at least 1°C, preferably at least 3°C, higher than the melting point of the crystalline material, and / or preferably, the temperature of the molten crude crystalline material is not more than 15°C, preferably not more than 10°C, higher than the melting point of the crystalline material.

[0053] Alternatively, in a preferred embodiment of the present invention, the temperature of the molten crude crystalline material is below the melting point of the crystalline material; preferably, the temperature of the molten crude crystalline material is at least 1°C, preferably at least 3°C, below the melting point of the crystalline material, and / or preferably, the temperature of the molten crude crystalline material is at most 15°C, preferably at most 10°C, below the melting point of the crystalline material.

[0054] In a preferred embodiment of the present invention, in step (1): The molten crude glycolide is added at a rate of 20% by weight to 500% by weight, preferably 50% by weight to 200% by weight, per hour relative to the weight of the solid-liquid mixture I. The addition rate is expressed as the added weight % per unit time relative to the weight of the solid-liquid mixture I; The temperatures of both solid-liquid mixture I and solid-liquid mixture II are 60° C. or lower, preferably 50° C. or lower. Since glycolide is prone to thermal degradation, solid-liquid mixture I needs to be kept at 60° C. or lower before addition.

[0055] When crude glycolide melt is added to solid-liquid mixture I at a constant rate, the temperature of the melt itself rises during the addition process, which can lead to exothermic crystallization during cooling, potentially heating the solid-liquid mixture. To stably control the temperature of the solid-liquid mixture, it is necessary to match the addition rate with the heat exchange (cooling) force to stabilize the crystallization-extraction process. The temperature of the solid-liquid mixture must be maintained within a desired temperature range for two reasons: to avoid thermal degradation of glycolide and to ensure a sufficient temperature difference for crystallization during cooling of the glycolide melt. Glycolic acid and glycolic acid oligomers (e.g., glycolic acid dimer) contained in crude glycolide can provide the alcoholic hydroxyl groups (initiator) and protonic acid (catalyst) necessary for the ring-opening polymerization of glycolide. At a certain temperature, e.g., above 60°C, the ring-opening polymerization reaction occurs significantly, producing glycolic acid oligomers with a high molecular weight (degree of polymerization of 7 or more). The ring-opening polymerization side reaction that occurs during the purification process is a typical thermal degradation reaction, and its degree of reactivity is affected by the initiator / catalyst concentration, temperature, and time. The resulting oligomers are generally difficult to remove because of their low solubility in common organic solvents.

[0056] In a preferred embodiment of the present invention, in step (1): The solid phase of the solid-liquid mixture I is glycolide crystals having a glycolide purity of more than 95%, preferably more than 99%. The liquid phase of the solid-liquid mixture I is a saturated solution of glycolide in an organic solvent. The organic solvent is a good solvent for common impurities in glycolide, such as at least one of acetone, ethyl acetate, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, tert-butanol, n-pentanol, and iso-pentanol. These organic solvents exhibit relatively high solubility for common impurities in crude glycolide, such as color impurities and acids. For example, common acid impurities include glycolic acid and linear glycolic acid dimers.

[0057] In a preferred embodiment of the present invention, in step (1): The weight content of the solid phase in the solid-liquid mixture I is 0.5% to 25%, preferably 2% to 25%; If the weight content of the solid phase in the solid-liquid mixture I is 0.5% or more, sufficient crystallization sites can be provided for crystallization when the molten crude glycolide is cooled.

[0058] The weight content of the solid phase in the solid-liquid mixture II is 50% or less, preferably 40% or less.

[0059] In a preferred embodiment of the present invention, in step (1), The median diameter of the solid phase in the solid-liquid mixture I is 200 microns or less, preferably 150 microns or less; The median diameter of the solid phase in the solid-liquid mixture II is 600 microns or less, preferably 500 microns or less; The relatively small particle size of the solid phase in solid-liquid mixture I facilitates stirring and dispersion to obtain a uniform solid-liquid mixture; Conventional techniques can be used to control the particle size of the solid phase in the solid-liquid mixture I. For example, crystal particles can be processed to a desired particle size by physical crushing and screening, and then added to a saturated solution to prepare a mixture. A stirring device whose main function is dispersion is preferably used for mixing. In the production equipment, the stirring speed is usually 200 rpm or less.

[0060] Without being bound by any known theory, it is believed that particles within the preferred particle size range in solid-liquid mixture I can be uniformly suspended in the solid-liquid mixture under agitation by a conventional agitating paddle, e.g., a pitched blade or helical impeller, and serve as sites for the melting and crystallization of the coarse crystalline material (e.g., glycolide) upon cooling. This avoids the occurrence of large crystallization sites at unfavorable locations, such as the vessel wall and the stirring paddle, and allows for the production of purified crystalline substance (e.g., glycolide) crystals with uniform particle size. For a given weight content of the solid phase in solid-liquid mixture I, a smaller particle size of the solid phase results in a larger number of particles in the solid-liquid mixture, providing more crystallization sites and favoring uniform crystallization. When the crystalline substance (e.g., crude glycolide) phase in the molten crystalline substance (e.g., crude glycolide) comes into contact with particles in solid-liquid mixture I, it continues to grow on the surface of these particles, resulting in a larger crystal particle size in solid-liquid mixture II. To ensure the efficiency of the extraction process, such as ensuring that impurities, such as coloring impurities and acid, are sufficiently dispersed in the organic solvent and that, for example, 80% or more of the acid is extracted into the organic solvent, it is necessary to minimize the particle size of glycolide crystals in solid-liquid mixture II.

[0061] In a preferred embodiment of the present invention, step (3) is carried out and: The solid-liquid separation method in step (2) is centrifugation or filtration; The drying of the solid phase in step (3) is by convection drying under a hot inert gas or by heat conduction drying under vacuum.

[0062] In a preferred embodiment of the present invention: Steps (1) and (2), and optionally step (3), are repeated at least once to obtain further purified glycolide crystals.

[0063] Another object of the present invention is to provide glycolide obtained by the above purification method.

[0064] Another object of the present invention is to provide the use of glycolide in the preparation of polyglycolic acid.

[0065] The purified glycolide crystals obtained in the present invention can be used as a polymerization monomer for polyglycolic acid.

[0066] Compared with the prior art, the present invention has the following beneficial effects: Unlike the prior art, which typically adds glycolide directly to the extraction solvent, the present invention adds a certain amount of solid particles of a crystalline substance (e.g., glycolide crystals) to the extraction solvent. These solid particles become crystallization sites for the melt of the crude crystalline substance (e.g., glycolide) during cooling. This prevents the formation of a large number of crystallization sites in undesirable locations, such as the vessel wall and stirring paddle, and allows the production of a purified crystalline substance (e.g., glycolide crystals) with a uniform particle size.

[0067] The solid-phase crystalline material (e.g., glycolide crystals) added in the present invention has a very small average particle size, which allows the newly formed crystals to be relatively small, facilitating the diffusion of impurities, such as coloring impurities and acids, into the organic solvent. As a result, the extraction efficiency is high and the acid content of the crystalline material (e.g., glycolide) is low. When used with glycolide, the method of the present invention reduces the acid content of glycolide using the same amount of organic solvent compared to the conventional method of directly adding molten glycolide to the extraction solvent. Since the main impurities in crude glycolide are acidic impurities, effective removal of these impurities allows the glycolide to be directly used in ring-opening polymerization. Furthermore, the purified glycolide exhibits higher purity.

[0068] In the present invention, a solid-liquid mixture is used to melt a crystalline substance (such as glycolide). Compared with the conventional recrystallization process, the present invention allows for a constant process temperature and no cooling process over a large temperature span, and has the advantages of simple operation, easy industrial scale-up, and low energy consumption.

[0069] [Example] The present invention will be described in detail below with specific examples. It should be noted that the following examples are only used to further explain the present invention and cannot be understood as limiting the protection scope of the present invention. Any insubstantial improvements and adjustments made to the present invention by those skilled in the art based on the content of the present invention still fall within the protection scope of the present invention.

[0070] The raw materials used in the examples are all conventional commercially available raw materials.

[0071] The mean particle size of glycolide crystals in the present invention was tested as follows: Using a Malvern Mastersizer 3000 laser particle size distribution analyzer, the average particle size (median size, i.e., the particle size at which the cumulative volume distribution of particles is 50%), D10 particle size (the volume content of particles smaller than this particle size is 10% of all particles), and D90 particle size (the volume content of particles smaller than this particle size is 90% of all particles) were measured. The smaller the ratio of D90 to D10, the narrower the particle size distribution. Isopropyl alcohol was used as the dispersion medium.

[0072] The free acid concentrations of crude glycolide and glycolide in the present invention were determined as follows: The free acid concentration in crude glycolide was measured by acid-base titration. The specific procedure was as follows: A crude glycolide sample was dissolved in approximately 30 mL of dry dimethyl sulfoxide. After complete dissolution, a few drops of bromophenol blue indicator solution were added to turn the solution yellow. The solution was titrated with a known concentration of dilute sodium hydroxide in benzyl alcohol until the color changed from yellow to green, indicating the endpoint. The terminal carboxyl group content (μmol) in glycolide was calculated based on the volume of sodium hydroxide solution consumed at the end of the titration. This value was divided by the weight of the crude glycolide sample to determine the free acid concentration (μmol / g) of crude glycolide.

[0073] The purity of glycolide in the present invention was measured as follows: The purity of glycolide was measured by gas chromatography (GC). 200 mg of glycolide sample to be tested and 40 mg of p-chlorobenzophenone as an internal standard were dissolved in 10 mL of acetone, and 2 μL of the solution was injected into the gas chromatograph to measure the glycolide content. The purity of glycolide was determined using a standard calibration curve prepared in advance using glycolide reference standards (at least five points between 160 mg and 200 mg) and the internal standard (40 mg), i.e., p-chlorobenzophenone. The measurement system was an Agilent 7890B, the chromatography column was a capillary column HP-5 (30 m × 0.32 mm, 0.25 μm), the chromatography column temperature was 280 °C, the injection port temperature was 150 °C, and the detector was an FID.

[0074] Example 1 Preparation of crude glycolide: 600 g of glycolic acid crystals and 6 g of tin octoate catalyst were added to a reactor. The temperature was raised from room temperature to 90°C, at which point the solids were completely dissolved, and then further raised to 120°C to perform atmospheric prepolymerization. After 2 hours of prepolymerization, the temperature was raised to 210°C, at which point water no longer distilled off. The system was maintained at that temperature, and while controlling the degree of vacuum in the system to 2 kPa (A), evacuation was continued until water no longer volatilized, yielding 475 g of glycolic acid oligomer.

[0075] The oligomer was transferred to a depolymerization reactor. This depolymerization system was reacted at a reaction temperature of 285°C, a vacuum of 3 kPa (A), and a stirring speed of 120 rpm to produce crude glycolide. The crude glycolide vapor generated in the depolymerization reactor was condensed in a spherical condenser with a jacket water temperature of 85°C to obtain molten crude glycolide. The reaction was stopped after 2 hours, yielding 395 g of crude glycolide with an acid content of 450 μmol / g and a glycolide purity of 90.20%.

[0076] Glycolide purification: An excess amount of solid glycolide (commercial product, acid content: 1.7 μmol / g, GC purity: 99.86%) was added to 600 g of ethyl acetate (commercial product, dehydrated with 3A molecular sieves) and thoroughly mixed at 10°C until dissolution equilibrium was achieved. The solid-liquid mixture was separated at 10°C to obtain a clear saturated solution. 100 g of solid glycolide was added to 500 g of this saturated solution to obtain solid-liquid mixture I.

[0077] 250 g of the above crude glycolide melt was maintained at 90°C in a jacketed reactor A. 600 g of solid-liquid mixture I was added to a jacketed reactor B, and 100 g of solid glycolide (median diameter 103 μm, median diameter deviation (D50 particle size deviation) 9.5% measured by sampling from the top and bottom of the reactor) was suspended therein, adjusting the acid content of the liquid phase to 0.15 μmol / g. The mixture was stirred at 120 rpm and maintained at 10°C. The melt from reactor A was added dropwise to reactor B at a rate of 70 wt% per hour based on the weight of the solid-liquid mixture. During this time, the stirring speed was 120 rpm, and the internal temperature (temperature of the material inside the reactor) was maintained at 12°C. Upon completion, a solid-liquid mixture with a solid content of 35.3 wt% was obtained. The filter cake was recovered by suction filtration under nitrogen protection. The median diameter of the glycolide crystals in the filter cake was 275 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured; the deviation was 15.0%), and the ratio of D90 to D10 was 3.9. The filter cake was dried under vacuum at 60° C. for 4 hours to obtain purified glycolide crystals with an acid content of 45 μmol / g and a purity of 98.0% as measured by GC.

[0078] Example 2 Crude glycolide was prepared as in Example 1.

[0079] Glycolide purification: An excess amount of solid glycolide (commercial product, acid content: 1.7 μmol / g) was added to 600 g of isopropanol (commercial product, dehydrated with 3A molecular sieves), and the mixture was thoroughly mixed at 35°C until dissolution equilibrium was achieved. The solid-liquid mixture was separated at 35°C to obtain a clear saturated solution. 30 g of solid glycolide was added to 500 g of the saturated solution to obtain solid-liquid mixture I.

[0080] 250 g of the above crude glycolide melt was maintained at 90°C in a jacketed reactor A. 530 g of a mixture of isopropanol and glycolide was added to a jacketed reactor B, and 30 g of solid glycolide (median diameter: 103 μm, deviation of the median diameter: 8.0%) was suspended therein, with the acid content of the liquid phase adjusted to 0.03 μmol / g. The mixture was stirred at 120 rpm and maintained at 35°C. The melt from reactor A was added dropwise to reactor B at a rate of 70 wt% per hour, based on the weight of the solid-liquid mixture. The stirring speed during this period was 120 rpm, and the internal temperature was maintained at 36°C. Upon completion, a solid-liquid mixture with a solid content of 31.7 wt% was obtained. The filter cake was recovered by suction filtration under nitrogen protection. The median diameter of the glycolide crystals in the filter cake was 300 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured; the deviation was 16.1%), and the D90 to D10 ratio was 4.3. The filter cake was vacuum-dried at 60°C for 4 hours to obtain purified glycolide crystals with an acid content of 42 μmol / g and a purity of 98.2% as measured by GC.

[0081] Example 3 Crude glycolide was prepared as in Example 1.

[0082] Glycolide purification: A saturated solution was prepared in the same manner as in Example 2. 15 g of solid glycolide was added to 500 g of the saturated solution to obtain solid-liquid mixture I.

[0083] 250 g of the above-mentioned crude glycolide melt was maintained at 90°C in a jacketed reactor A. 515 g of a mixture of isopropanol and glycolide was added to a jacketed reactor B, and 15 g of solid glycolide (median diameter: 103 μm, deviation of the median diameter: 6.2%) was suspended therein, with the acid content of the liquid phase adjusted to 0.03 μmol / g. The mixture was stirred at 120 rpm and maintained at 35°C. The melt from reactor A was added dropwise to reactor B at a rate of 70 wt% per hour, based on the weight of the solid-liquid mixture. The stirring speed during this period was 120 rpm, and the internal temperature was maintained at 36°C. Upon completion, a solid-liquid mixture with a solid content of 30.4 wt% was obtained. The filter cake was recovered by suction filtration under nitrogen protection. The median diameter of the glycolide crystals in the filter cake was 500 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured; the deviation was 17.9%), and the D90 to D10 ratio was 4.7. The filter cake was dried in vacuo at 60°C for 4 hours to obtain purified glycolide crystals with an acid content of 75 μmol / g and a purity of 97.1% as measured by GC.

[0084] Example 4 Crude glycolide was prepared as in Example 1.

[0085] Glycolide purification: An excess amount of solid glycolide (commercial product, acid content: 1.7 μmol / g, GC purity: 99.86%) was added to 600 g of ethanol (commercial product, dehydrated with 3A molecular sieves) and thoroughly mixed at 45°C until dissolution equilibrium was achieved. The solid-liquid mixture was separated at 45°C to obtain a clear saturated solution. 75 g of solid glycolide was added to 375 g of the saturated solution to obtain solid-liquid mixture I.

[0086] 250 g of the crude glycolide melt from above was maintained at 90°C in a jacketed reactor A. 450 g of a mixture of ethanol and glycolide was added to a jacketed reactor B, and 75 g of glycolide solids (median diameter 103 μm, deviation of median diameter 10.1%) was suspended therein, resulting in an acid content of 0.06 μmol / g in the liquid phase. The mixture was stirred at 120 rpm and maintained at 45°C. The melt from reactor A was added dropwise to reactor B at a rate of 70 wt% per hour, based on the weight of the solid-liquid mixture, while the stirring speed was 120 rpm and the internal temperature was maintained at 48°C. Upon completion, a solid-liquid mixture with a solid content of 40.0 wt% was obtained. The filter cake was recovered by suction filtration under nitrogen protection. The median diameter of the glycolide crystals in the filter cake was 268 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured; the deviation was 13.2%), and the ratio of D90 to D10 was 5.2. The filter cake was dried under vacuum at 60°C for 4 hours to obtain purified glycolide crystals with an acid content of 73 μmol / g and a purity of 97.5% as measured by GC.

[0087] Example 5 The purified glycolide crystals (GC purity: 98.0%) obtained in Example 1 were subjected to secondary purification.

[0088] Secondary purification of glycolide: A saturated solution was prepared in the same manner as in Example 1. 60 g of solid glycolide was added to 300 g of the saturated solution to obtain solid-liquid mixture I.

[0089] 150 g of purified glycolide crystals obtained in Example 1 were heated and melted, and the melt was maintained at 90°C in a jacketed reactor A. 360 g of a solid-liquid mixture I of ethyl acetate and glycolide was added to a jacketed reactor B, and 60 g of solid glycolide (median diameter 103 μm, median diameter deviation 10.6%, GC purity 99.86%) was suspended therein. The acid content of the liquid phase was 0.14 μmol / g. The mixture was stirred at 120 rpm and maintained at 10°C. The melt from reactor A was added dropwise to reactor B at a rate of 70 wt% per hour based on the weight of the solid-liquid mixture. The stirring speed during this period was 120 rpm, and the internal temperature was maintained at 12°C. Upon completion, a solid-liquid mixture with a solid content of 37.6 wt% was obtained. The filter cake was recovered by suction filtration under nitrogen protection. The median diameter of the glycolide crystals in the filter cake was measured to be 295 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured with a deviation of 14.4%), and the ratio of D90 to D10 was 3.6. The filter cake was dried under vacuum at 60° C. for 4 hours to obtain purified glycolide crystals with an acid content of 2.8 μmol / g and a purity of 99.6% as measured by GC.

[0090] Preparation of polyglycolic acid: 55 g of purified glycolide from Example 5 was weighed and added to a reactor. 0.006 wt. % trichlorophosphoric acid dihydrate (commercially available) and 0.1 wt. % initiator lauryl alcohol (commercially available) were weighed and added to the reactor. The reactor was evacuated and then purged with nitrogen. This evacuation-nitrogen purging procedure was repeated once, and finally the reactor was evacuated again to reduce the pressure inside the reactor to less than 200 Pa (A). The reactor was then closed and reacted under stirring. The reactor temperature was initially heated to 160°C, then increased at a rate of 4°C / min, and finally maintained at 220°C. After reacting for 60 minutes, the mixture was discharged to obtain polyglycolic acid.

[0091] The intrinsic viscosity of the polyglycolic acid was measured to be 1.60 dL / g.

[0092] Example 6 The purified glycolide crystals (GC purity: 98.2%) obtained in Example 2 were subjected to secondary purification.

[0093] Secondary purification of glycolide: A saturated solution was prepared in the same manner as in Example 2. 18 g of solid glycolide was added to 300 g of the saturated solution to obtain solid-liquid mixture I.

[0094] 150 g of purified glycolide crystals obtained in Example 2 were heated and melted, and the melt was maintained at 90°C in jacketed reactor A. 318 g of a mixture of isopropanol and glycolide was added to jacketed reactor B, and 18 g of solid glycolide (median diameter 103 μm, median diameter deviation 8.5%, GC purity 99.86%) was suspended therein. The acid content of the liquid phase was 0.03 μmol / g. The mixture was stirred at 120 rpm and maintained at 35°C. The melt from reactor A was added dropwise to reactor B at a rate of 70 wt% per hour, based on the weight of the solid-liquid mixture. The stirring speed during this period was 120 rpm, and the internal temperature was maintained at 36°C. Upon completion, a solid-liquid mixture with a solid content of 34.6 wt% was obtained. Under nitrogen protection, the filter cake was recovered by suction filtration. The median diameter of the glycolide crystals in the filter cake was measured to be 340 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured with a deviation of 15.4%), and the ratio of D90 to D10 was 4.0. The filter cake was dried under vacuum at 60°C for 4 hours to obtain purified glycolide crystals with an acid content of 3.2 μmol / g and a purity of 99.5% as measured by GC.

[0095] Preparation of polyglycolic acid: Polyglycolic acid was prepared in the same manner as in Example 5, except that 55 g of the purified glycolide of Example 6 was weighed and added to the reactor. The intrinsic viscosity of the polyglycolic acid was measured to be 1.58 dL / g.

[0096] Example 7 Preparation of crude glycolide: The differences from Example 1 were that the depolymerization system was reacted at a reaction temperature of 255°C, the vapor of crude glycolide generated in the depolymerization reactor was condensed using a spherical condenser with a jacket water temperature of 7°C to obtain solid crude glycolide, and the reaction was stopped after 4 hours to obtain 372 g of crude glycolide with an acid content of 570 μmol / g and a glycolide purity of 86.0%; Except for the above differences, the results were the same as in Example 1.

[0097] Glycolide purification: A solid-liquid mixture I was prepared in the same manner as in Example 1, except that a different solid glycolide (commercially available product, acid content: 6.0 μmol / g, GC purity: 99.30%) was used.

[0098] 250 g of solid crude glycolide was heated to a melt and maintained at 93°C in a jacketed reactor A. 600 g of a solid-liquid mixture I of ethyl acetate and glycolide was added to a jacketed reactor B, and 100 g of solid glycolide (measured by sampling from the top and bottom of the reactor, the median diameter was 145 μm, the deviation in the median diameter was 13.0%, and the GC purity was 99.30%) was suspended therein. The acid content of the liquid phase was 0.52 μmol / g. The mixture was stirred at 120 rpm and maintained at 10°C. The melt from reactor A was added dropwise to reactor B at a rate of 50 wt% per hour based on the weight of the solid-liquid mixture. The stirring speed during this period was 120 rpm, and the internal temperature was maintained at 12°C. Upon completion of the addition, a solid-liquid mixture with a solid content of 32.5 wt% was obtained. The filter cake was recovered by suction filtration under nitrogen protection. The median diameter of the glycolide crystals in the filter cake was measured to be 293 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured with a deviation of 17.5%), and the D90 to D10 ratio was 3.8. The filter cake was dried under vacuum at 60°C for 4 hours to obtain purified glycolide crystals with an acid content of 72 μmol / g and a purity of 96.8% as measured by GC.

[0099] Example 8 Crude glycolide was prepared as in Example 7.

[0100] Glycolide purification: The only difference from Example 7 was that the melt from Reactor A was added dropwise to Reactor B at a rate of 190 wt. % per hour based on the weight of the solid-liquid mixture, and the internal temperature was increased to a maximum of 14.8°C during the addition of the melt. Upon completion, a solid-liquid mixture with a solid content of 33.0 wt. % was obtained. The median diameter of the glycolide crystals in the filter cake was 318 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured; the deviation was 19.3%), the ratio of D90 to D10 was 4.5, the acid content of the purified glycolide crystals was 77 μmol / g, and the purity measured by GC was 96.5%; Except for the above differences, the rest was the same as in Example 7.

[0101] Example 9 Crude glycolide was prepared as in Example 7.

[0102] Glycolide purification: The only difference from Example 7 was that the melt from Reactor A was added dropwise to Reactor B at a rate of 120 wt. % per hour based on the weight of the solid-liquid mixture, and the internal temperature was increased to a maximum of 13.5°C during the addition of the melt. Upon completion, a solid-liquid mixture with a solid content of 32.9 wt. % was obtained. The median diameter of glycolide crystals in the filter cake was 305 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured with a deviation of 18.2%), the ratio of D90 to D10 was 4.2, the acid content of the purified glycolide crystals was 76 μmol / g, and the purity measured by GC was 96.6%; Except for the above differences, the rest was the same as in Example 7.

[0103] Example 10 Crude glycolide was prepared as in Example 7.

[0104] Glycolide purification: The only difference from Example 7 was that 250 g of solid crude glycolide was heated and melted, and the melt was maintained at 80°C in jacketed reactor A; after completion, a solid-liquid mixture with a solid content of 32.8 wt% was obtained. The median diameter of glycolide crystals in the filter cake was 290 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured; the deviation was 16.7%), the ratio of D90 to D10 was 5.0, the acid content of the refined glycolide crystals was 70 μmol / g, and the purity measured by GC was 96.8%; Except for the above differences, the rest was the same as in Example 7.

[0105] Example 11 Crude glycolide was prepared as in Example 7.

[0106] Glycolide purification: The only difference from Example 7 was that 600 g of a solid-liquid mixture I of ethyl acetate and glycolide was added to the jacketed reactor B, and the amount of solid glycolide suspended in the mixture was 140 g; after completion, a solid-liquid mixture with a solid content of 37.6 wt % was obtained. The median diameter of the glycolide crystals in the filter cake was 279 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured with a deviation of 15.5%), the ratio of D90 to D10 was 3.7, the acid content of the purified glycolide crystals was 68 μmol / g, and the purity measured by GC was 96.8%; Except for the above differences, the rest was the same as in Example 7.

[0107] Example 12 The difference from Example 7 is that the crude glycolide was changed; The crude glycolate used in the present invention was glycolate prepared according to the method described in Example 1 of invention patent CN107868075A (conventional purification method), with an acid content of 12.0 μmol / g and a GC purity of 98.9%; Except for the above differences, the other purification steps were the same as in Example 7; After the glycolide was purified, a solid-liquid mixture with a solid content of 35.3 wt% was obtained. The median diameter of the glycolide crystals in the filter cake was 311 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured; the deviation was 14.8%). The D90 to D10 ratio was 3.7. The acid content of the purified glycolide crystals was 0.80 μmol / g. The purity, as measured by GC, was 99.7%.

[0108] Preparation of polyglycolic acid: Polyglycolic acid was prepared in the same manner as in Example 5, except that 55 g of the purified glycolide of Example 12 was weighed and added to the reactor. The intrinsic viscosity of the polyglycolic acid was measured to be 1.67 dL / g.

[0109] Example 13 Preparation of crude L-lactide: According to the oligomerization-depolymerization method described in Reference 1 of the invention patent CN106397388A, crude L-lactide with an acid content of 275.0 μmol / g and a GC purity of 94.5% was prepared using L-lactic acid as raw material; Purification of L-lactide: An excess amount of the above solid crude L-lactide (acid content: 275.0 μmol / g, GC purity: 94.5%) was added to 600 g of isopropanol (commercially available, dehydrated with 3A molecular sieves) and thoroughly mixed at 35°C until dissolution equilibrium was achieved. The solid-liquid mixture was subjected to solid-liquid separation at 35°C to obtain a clear saturated solution. 32 g of solid lactide was added to 498 g of the saturated solution to obtain solid-liquid mixture I.

[0110] 250 g of the above crude lactide melt was maintained at 100°C in jacketed reactor A. 530 g of a mixture of isopropanol and lactide was added to jacketed reactor B, in which approximately 30 g of solid glycolide (median diameter 139 μm, deviation of median diameter 8.9%, measured by sampling from the top and bottom of the reactor) was suspended. The acid content of the liquid phase was 16.0 μmol / g. This mixture was stirred at 120 rpm and maintained at 35°C. The melt from reactor A was added dropwise to reactor B at a rate of 70 wt% per hour, based on the weight of the solid-liquid mixture. During this time, the stirring speed was 120 rpm, and the internal temperature was maintained at 37°C. Upon completion, a solid-liquid mixture with a solid content of 32.2 wt% was obtained. The filter cake was recovered by suction filtration under nitrogen protection. The median diameter of the lactide crystals in the filter cake was measured to be 337 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured with a deviation of 18.0%), and the ratio of D90 to D10 was 4.6. The filter cake was vacuum dried at 60°C for 4 hours to obtain purified lactide crystals with an acid content of 15 μmol / g and a purity of 98.9% as measured by GC.

[0111] Preparation of polylactic acid: 55 g of purified L-lactide from Example 13 was weighed and added to a reactor. 0.02 wt % tin isooctanoate (commercially available) and 0.1 wt % initiator lauryl alcohol (commercially available) were also weighed and added to the reactor. The reactor was evacuated and then purged with nitrogen. This evacuation-nitrogen purging procedure was repeated once, and finally the reactor was evacuated again to reduce the pressure inside the reactor to less than 200 Pa. The reactor was then closed and reacted with stirring. The reactor temperature was initially heated to 130°C, then increased at a rate of 4°C / min, and finally maintained at 190°C. After reacting for 60 minutes, the contents were discharged to obtain polylactic acid.

[0112] The intrinsic viscosity of the polylactic acid was measured and found to be 1.02 dL / g.

[0113] Example 14 Preparation of crude ε-caprolactam: Crude ε-caprolactam in the molten state with a GC purity of 99.2% was obtained by vapor-phase Beckmann rearrangement of cyclohexanone oxime and simple distillation, which is the reaction method described in Example 1 of invention patent CN101070298A.

[0114] Purification of ε-caprolactam: An excess amount of the above-mentioned molten crude ε-caprolactam (GC purity: 99.2%) was added to 600 g of isopropyl ether (commercial product), and the mixture was thoroughly mixed at 25°C until dissolution equilibrium was reached. The solid-liquid mixture was subjected to solid-liquid separation at 25°C to obtain a transparent saturated solution. The above-mentioned molten crude ε-caprolactam was then cooled to room temperature, and 30 g of the resulting solid was then crushed and added to 500 g of the saturated solution to obtain solid-liquid mixture I.

[0115] 250 g of the above crude ε-caprolactam melt was maintained at 75°C in a jacketed reactor A. 530 g of a mixture of isopropyl ether and ε-caprolactam was added to a jacketed reactor B, in which approximately 30 g of solid ε-caprolactam (median diameter 97 μm, deviation of the median diameter 6.5%, measured by sampling from the top and bottom of the reactor) was suspended. The mixture was stirred at 120 rpm and maintained at 25°C. The melt from reactor A was added dropwise to reactor B at a rate of 35 wt% per hour, based on the weight of the solid-liquid mixture. During this time, the stirring speed was 120 rpm, and the internal temperature was maintained at 25°C. Upon completion, a solid-liquid mixture with a solid content of 35.3 wt% was obtained. The filter cake was recovered by filtration under nitrogen protection. The median diameter of the ε-caprolactam crystals in the filter cake was measured to be 308 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, the filter cake was recovered by suction filtration, and the median diameter of the crystals in the filter cake was measured with a deviation of 12.9%), and the ratio of D90 to D10 was 4.2. The filter cake was vacuum-dried at 50°C for 4 hours to obtain purified ε-caprolactam crystals with a purity of 99.8% as measured by GC.

[0116] Example 15 Preparation of crude trioxane: Trioxane feed gas from the top of the distillation column of a trioxane synthesis apparatus (overhead operating temperature: 117°C) was condensed to 75°C to obtain molten crude trioxane with a purity of 98.5%.

[0117] Purification of trioxane: An excess amount of the above-mentioned molten crude trioxane (GC purity: 98.5%) was added to 600 g of benzene (commercial product), and the mixture was thoroughly mixed at 8°C until dissolution equilibrium was reached. This solid-liquid mixture was subjected to solid-liquid separation at 8°C to obtain a clear saturated solution. The above-mentioned molten crude trioxane was then cooled to room temperature, and 30 g of the resulting solid was then crushed and added to 500 g of the saturated solution to obtain solid-liquid mixture I.

[0118] 250 g of the above crude trioxane melt was maintained at 66°C in a jacketed reactor A. 530 g of a mixture of benzene and trioxane was added to a jacketed reactor B, in which approximately 30 g of solid trioxane (median diameter 75 μm, deviation of the median diameter 6.3%, measured by sampling from the top and bottom of the reactor) was suspended. The mixture was stirred at 120 rpm and maintained at 8°C. The melt from reactor A was added dropwise to reactor B at a rate of 35 wt% per hour, based on the weight of the solid-liquid mixture. During this time, the stirring speed was 120 rpm, and the internal temperature was maintained at 8°C. Upon completion, a solid-liquid mixture with a solid content of 32.7 wt% was obtained. The filter cake was recovered by suction filtration under nitrogen protection. The median diameter of the trioxane crystals in the filter cake was measured to be 242 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured with a deviation of 9.5%), and the ratio of D90 to D10 was 3.9. The filter cake was vacuum-dried at 55° C. for 4 hours to obtain purified trioxane crystals with a purity of 99.7% as measured by GC.

[0119] Comparative Example 1 Preparation of crude glycolide: In the same manner as in Example 1, crude glycolide having an acid content of 450 μmol / g and a glycolide purity of 90.20% was prepared.

[0120] Glycolide purification: 250 g of the above crude glycolide melt was placed in a jacketed reactor A and maintained at 90°C. 500 g of ethyl acetate was added to a jacketed reactor B, which was stirred at 120 rpm and maintained at 10°C. The melt from reactor A was transferred to reactor B at a dropwise addition rate of 70% by weight per hour, based on the weight of the solvent. During this time, the stirring speed was 120 rpm, and the internal temperature was maintained at 12°C. Upon completion, a solid-liquid mixture with a solid content of 25.1% by weight was obtained. Suction filtration was performed under nitrogen protection, and the filter cake was recovered. The median diameter of the glycolide crystals in the filter cake was measured to be 725 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured, with a deviation of 31.3%), and the D90 to D10 ratio was 11.1. The filter cake was vacuum dried at 60°C for 4 hours to obtain purified glycolide crystals with an acid content of 123 µmol / g and a purity of 96.5% as determined by GC.

[0121] Comparative Example 2 The purified glycolide crystals (GC purity: 96.5%) obtained in Comparative Example 1 were subjected to secondary purification.

[0122] Secondary purification of glycolide: 150 g of purified glycolide crystals obtained in Comparative Example 1 were heated and melted, and the melt was maintained at 90°C in a jacketed reactor A. 300 g of ethyl acetate was added to a jacketed reactor B, which was stirred at 120 rpm and maintained at 10°C. The melt from reactor A was transferred to reactor B at a dropwise addition rate of 70 wt% per hour based on the weight of the solvent. During this time, the stirring speed was 120 rpm and the internal temperature was maintained at 12°C. Upon completion, a solid-liquid mixture with a solid content of 26.9 wt% was obtained. The filter cake was recovered by suction filtration under nitrogen protection. The median diameter of the glycolide crystals in the filter cake was measured to be 843 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured with a deviation of 34.7%), and the D90 to D10 ratio was 8.5. The filter cake was dried under vacuum at 60°C for 4 hours to obtain purified glycolide crystals with an acid content of 18.1 µmol / g and a purity of 98.5% as determined by GC.

[0123] Preparation of polyglycolic acid: Polyglycolic acid was prepared in the same manner as in Example 5, except that 55 g of the purified glycolide of Comparative Example 2 was weighed and added to the reactor; the intrinsic viscosity of the polyglycolic acid was measured to be 0.95 dL / g.

[0124] Comparative Example 3 Preparation of crude glycolide: In the same manner as in Example 1, crude glycolide having an acid content of 450 μmol / g and a glycolide purity of 90.20% was prepared.

[0125] Glycolide purification: 250 g of the above-mentioned crude glycolide melt was maintained at 90°C in a jacketed reactor A. 500 g of ethyl acetate was added to the jacketed reactor A, stirred at 120 rpm, and maintained at 60°C for 30 minutes to prepare a solution. The solution in reactor A was cooled to an internal temperature of 12°C at a rate of 12°C per hour. During this time, the stirring speed was 120 rpm. The internal temperature of the solid-liquid mixture was maintained at 12°C for 30 minutes to allow complete precipitation of crystals. Upon completion, a solid-liquid mixture with a solid content of 23.6 wt% was obtained. The filter cake was recovered by suction filtration under nitrogen protection. The median diameter of the glycolide crystals in the filter cake was measured to be 692 μm (samples of the solid-liquid mixture were taken from the top and bottom of the reactor, and the filter cake was recovered by suction filtration. The median diameter of the crystals in the filter cake was measured with a deviation of 28.2%), and the D90 to D10 ratio was 10.7. The filter cake was dried under vacuum at 60° C. for 4 hours to obtain purified glycolide crystals with an acid content of 108 μmol / g and a purity of 96.9% as determined by GC.

[0126] In Comparative Example 1, glycolide was purified by a conventional method. Comparing Example 1 and Comparative Example 1, the median diameter of the purified solid phase was 275 μm and 725 μm, the acid content was 45 μmol / g and 123 μmol / g, the ratio of D90 to D10 was 3.9 and 11.1, and the GC purity was 98.0% and 96.5%, respectively; In Comparative Example 2, the glycolide obtained in Comparative Example 1 was subjected to secondary purification by a conventional method. In Example 5, the glycolide obtained in Example 1 was subjected to secondary purification by the method of the present invention. Comparing Example 5 and Comparative Example 2, the median diameter of the purified solid phase was 295 μm and 843 μm, the acid content was 2.8 μmol / g and 18.1 μmol / g, the ratio of D90 to D10 was 3.6 and 8.5, and the GC purity was 99.6% and 98.5%, respectively; From the comparison of the above data, it can be seen that the purification method of the present invention can obtain a purified solid phase with a smaller median diameter, a lower acid content, a more uniform particle size distribution, and higher purity, compared with the conventional purification methods in the prior art. The method of the present invention can also be used for secondary purification, and the glycolide obtained after secondary purification has better properties.

[0127] In Example 12, glycolide with a GC purity of 98.9% obtained by a conventional purification method was further purified. The resulting glycolide had a median diameter of 311 μm, a D90 to D10 ratio of 3.7, an acid content of the purified glycolide crystals of 0.80 μmol / g, and a purity measured by GC of 99.7%. This further demonstrates that glycolide can be purified to a higher purity, with a reduced acid content and improved purity, according to the present invention.

[0128] The test results demonstrated that the glycolide purified in Examples 1 to 12 had small, uniform particle sizes, low acid contents, and high purity. Furthermore, the present invention uses a solid-liquid mixture to receive the glycolide melt. Compared with conventional recrystallization processes, the present invention allows for a constant process temperature, no cooling process over a large temperature span, simple operation, and low energy consumption, making it suitable for industrialization.

Claims

1. 1. A phase change-diffusion coupled crystallization method for purifying a crystalline material, comprising the steps of: (1) a step of adding a crude crystalline substance in a molten state to a solid-liquid mixture I in a dissolution equilibrium state to obtain a solid-liquid mixture II; wherein the solid-liquid mixtures I and II each comprise a solid phase and a solution phase, the solid phase comprising a crystalline substance in a solid state and may comprise impurities, and the solution phase comprising a solvent and a crystalline substance in a molten state and may comprise impurities; and (2) A step of subjecting the solid-liquid mixture II to solid-liquid separation.

2. 2. The method of claim 1, wherein the molten coarse crystalline material has a temperature higher than the temperature of the solid-liquid mixture I, and the temperature difference is sufficient to cause and complete a phase transition in the molten coarse crystalline material.

3. 3. The method according to claim 1 or 2, wherein the crystalline material in the solid phase of the solid-liquid mixture I has a purity higher than the purity of the crude crystalline material in the molten state, and the difference in purity is sufficient to allow an effective amount of impurities in the crude crystalline material in the molten state to diffuse into the solvent.

4. 10. A method according to any one of the preceding claims, characterized in that: In step (1), the coarse crystalline substance in a molten state is added to the solid-liquid mixture I in a melt equilibrium state in a manner and at a rate such that the temperature during the transformation from solid-liquid mixture I to solid-liquid mixture II does not change or does not change substantially, or changes by 10°C or less, preferably 5°C or less, more preferably 3°C or less; Preferably, the molten coarse crystalline material is added to the solid-liquid mixture II by a method selected from at least one of dropwise addition, injection, spraying, sparging, and atomization.

5. 5. The method according to claim 4, characterized in that the device containing the solid-liquid mixture I in step (1) is equipped with a heat exchange device for removing the heat caused by the addition of the coarse crystalline substance in the molten state, for example a jacket or coil in which a cooling medium, for example water, is used.

6. 10. The method according to any one of the preceding claims, characterized in that the temperature difference between the coarse crystalline material in the molten state and the solid-liquid mixture I and / or the solid-liquid mixture II is at least 15°C, preferably at least 25°C; and at most 85°C, for example at most 75°C.

7. 10. The method according to any one of the preceding claims, characterized in that the temperature of the solid-liquid mixture I and / or the solid-liquid mixture II is 4°C or higher.

8. 10. A method according to any one of the preceding claims, characterized in that the temperature of the molten crude crystalline material is equal to or higher than the melting point of the crystalline material; preferably the temperature of the molten crude crystalline material is at least 1°C, preferably at least 3°C, higher than the melting point of the crystalline material, and / or preferably the temperature of the molten crude crystalline material is not more than 15°C, preferably not more than 10°C, higher than the melting point of the crystalline material.

9. 10. A method according to any one of the preceding claims, characterized in that the temperature of the molten crude crystalline material is below the melting point of the crystalline material; preferably the temperature of the molten crude crystalline material is at least 1°C, preferably at least 3°C, lower than the melting point of the crystalline material, and / or preferably the temperature of the molten crude crystalline material is at most 15°C, preferably at most 10°C, lower than the melting point of the crystalline material.

10. The solid-liquid mixture I and / or the solid-liquid mixture II is a suspension; The method according to any one of the preceding claims, characterized in that preferably the solid phase in the solid-liquid mixtures I and II is uniformly dispersed, and when two different samples of the solid-liquid mixture are taken from any two different positions in the solid-liquid mixture I and the D50 particle size is measured, the deviation in D50 particle size between the two different samples of the solid-liquid mixture is 30% or less, preferably 20% or less; and / or when two different samples of the solid-liquid mixture are taken from any two different positions in the solid-liquid mixture II and the D50 particle size is measured, the deviation in D50 particle size between the two different samples of the solid-liquid mixture is 30% or less, preferably 20% or less.

11. 10. The method according to any one of the preceding claims, characterized in that the ratio of D90 to D10 of the solid phase of the solid-liquid mixture I and / or solid-liquid mixture II, respectively, is 10 or less, preferably 7 or less, more preferably 5 or less.

12. 10. A method according to any one of the preceding claims, wherein the crystalline material is a cyclic monomer having a melting point above -20°C, preferably selected from lactones (e.g. caprolactone, glycolide, lactide, 1,4-dioxan-2-one), cyclic formals (e.g. trioxane), and lactams (e.g. caprolactam), preferably a lactide compound, e.g. glycolide or lactide.

13. the crystalline material is glycolide; the crude crystalline material in a molten state is unpurified crude crystalline material in a molten state and / or purified crude crystalline material in a molten state; and / or 10. The method according to any one of the preceding claims, wherein the mass content of glycolide in the molten crude glycolide is between 85% and 99%.

14. The temperature of the molten crude glycolide is between 75°C and 120°C, preferably between 80°C and 95°C; and / or 14. The method according to claim 13, characterized in that the temperature of the molten purified crude glycolide is between 80°C and 120°C, preferably between 85°C and 95°C.

15. In step (1), The molten crude glycolide is added at a rate of 20% to 500% by weight, preferably 50% to 200% by weight, per hour, based on the weight of the solid-liquid mixture I; and / or 14. The method according to claim 13, characterized in that the temperature of both the solid-liquid mixture I and the solid-liquid mixture II is not more than 60°C, preferably not more than 50°C.

16. In step (1), The solid phase of the solid-liquid mixture I is glycolide crystals having a glycolide purity of more than 95%, preferably glycolide crystals having a glycolide purity of more than 99%; and / or 14. The method according to claim 13, wherein the liquid phase of the solid-liquid mixture I is a saturated solution of glycolide in an organic solvent, the organic solvent preferably being at least one of acetone, ethyl acetate, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, tert-butanol, n-pentanol and iso-pentanol.

17. In step (1), the weight content of the solid phase in said solid-liquid mixture I is between 0.5% and 25%; preferably between 2% and 25%; and / or 10. The method according to claim 1, wherein the weight content of the solid phase in the solid-liquid mixture II is less than or equal to 50%, preferably less than or equal to 40%.

18. In step (1), The median diameter of the solid phase in the solid-liquid mixture I is 200 microns or less, preferably 150 microns or less; and / or 10. The method according to any one of the preceding claims, characterized in that the median diameter of the solid phase in said solid-liquid mixture II is less than or equal to 600 microns, preferably less than or equal to 500 microns.

19. The method of solid-liquid separation in step (2) is centrifugation or filtration; and / or 10. The method according to any one of the preceding claims, characterized in that the method further comprises step (3): drying the solid phase separated in step (2) and subsequently recovered, wherein the method of drying is convection drying under hot inert gas or heat conduction drying under vacuum.

20. 10. The method of any one of the preceding claims, wherein the method is carried out repeatedly, for example 2, 3, 4 or 5 times; wherein the purified crystalline material obtained from a previous run of the method is melted to serve as the molten crude crystalline material for a next run of the method.

21. Use of glycolide prepared by the method according to any one of claims 13 to 16 in the preparation of polyglycolic acid.

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