Recrystallization method of p-dioxanone

Abstract

The invention provides a p-dioxanone recrystallization method which comprises the following steps: (1) vacuumizing a p-dioxanone crude product at a certain temperature to obtain a mixture of PDO crystals and liquid, heating the separated PDO crystals at normal pressure for sweating, and taking the re-separated PDO crystals as recrystallization seed crystals; (2) mixing aliphatic ester, liquid alkane and p-dioxanone, cooling the mixed solution to a certain temperature, adding the seed crystal prepared in the step (1), and carrying out primary constant-temperature crystallization; (3) cooling the crystallization liquid, carrying out secondary constant-temperature crystallization, and separating out PDO crystals; (4) cooling the separated PDO crystal and aliphatic ester, and cleaning the PDO crystal with low-temperature aliphatic ester; and (5) carrying out reduced pressure distillation on the cleaned PDO crystal to obtain a high-purity p-dioxanone product. The method has good purification effect and yield of the p-dioxanone, the purity of the p-dioxanone in the purified product is greater than 99.9%, and the mass yield of the p-dioxanone is greater than 60%.

Description

Technical Field

[0001] This invention relates to the field of organic purification technology, specifically to a method for recrystallizing p-dioxanone. Background Technology

[0002] p-Dioxane is primarily used to polymerize and prepare high-molecular-weight poly(p-dioxane). Poly(p-dioxane) belongs to the α-polyester class of polymers. Its synthesis process was patented in the United States in 1979 and approved by the U.S. Food and Drug Administration (FDA). It is widely used in bioabsorbable surgical sutures, thus partially replacing PGA and PLA as surgical suture materials. In the 1970s, Ethicon in the United States successfully prepared biodegradable surgical sutures using poly(p-dioxane), commercially known as PDS. Compared with Dexon surgical sutures made from PGA and Vicryl surgical sutures made from PLGA, PDS has the advantage of being able to prepare monofilament sutures due to its superior toughness. Furthermore, it retains high tensile strength and knot strength during degradation. Besides its successful application in surgical sutures, poly(p-dioxane) is also used in orthopedic fixation materials, tissue repair materials, cell scaffolds, and drug carriers.

[0003] To obtain high molecular weight poly(p-dioxanone), the p-dioxanone monomer must have very high purity, generally greater than 99.9%. Purifying crude p-dioxanone using distillation is difficult to achieve a purity greater than 99.9%. Repeated vacuum distillation of the product obtained from the distillation section, collecting distillate fractions within a certain boiling range under a specific vacuum, can yield a product with a purity greater than 99.9%, but the yield is very low. Furthermore, some impurities with boiling points close to p-dioxanone are difficult to remove by distillation. European patent EP0617029A1 discloses a method for recrystallizing and purifying p-dioxanone, but this requires two recrystallizations at -20°C or even lower, which is inconvenient and yields low results. Summary of the Invention

[0004] The purpose of this invention is to provide a method for recrystallizing p-dioxanone, which purifies p-dioxanone to meet the requirements for preparing poly-p-dioxanone, while achieving a high purification yield.

[0005] The technical solution of this invention is as follows: The present invention provides a method for recrystallizing dioxane, comprising the following steps: (1) Vacuum the crude p-dioxanone product at a certain temperature to obtain a mixture of p-dioxanone crystals and liquid. Heat the separated p-dioxanone crystals to a certain temperature under normal pressure to sweat, and separate the p-dioxanone crystals again as seed crystals for recrystallization. (2) Mix low-boiling-point aliphatic esters, low-boiling-point liquid alkanes and crude p-dioxanone in proportion. After cooling the mixture to a certain temperature, add the seed crystals prepared in step (1) and carry out a constant-temperature crystallization. (3) The crystallization solution from step (2) is slowly cooled to a certain temperature and subjected to secondary isothermal crystallization, and then the p-dioxanone crystals are separated. (4) Cool the p-dioxanone crystals separated in step (3) and the aliphatic esters mentioned in step (2) to a certain temperature, and clean the p-dioxanone crystals with low-temperature aliphatic esters. (5) The cleaned p-dioxanone crystals were distilled under reduced pressure to obtain a high-purity p-dioxanone product.

[0006] The purity of the crude p-dioxanone in step (1) is preferably 98.2-99.7%. When the purity of the crude p-dioxanone is less than 98.2%, p-dioxanone seed crystals with a purity greater than 99.8% cannot be obtained through step (1), and p-dioxanone products with a purity greater than 99.9% cannot be obtained through steps (1) to (5).

[0007] In the preferred step (1), the vacuum temperature is 20~26℃ and the vacuum degree is 10~50mbar. When the vacuum conditions do not meet the preferred conditions, p-dioxanone seed crystals with a purity greater than 99.8% cannot be obtained through step (1).

[0008] In the preferred step (1), the sweating temperature is 27~32℃ and the sweating time is 0.5~1.5h. When the sweating conditions do not meet the preferred conditions, p-dioxanone seed crystals with a purity greater than 99.8% cannot be obtained through step (1).

[0009] The preferred low-boiling-point aliphatic ester mentioned in step (2) is at least one of methyl formate, ethyl formate, propyl formate, methyl acetate, ethyl acetate and methyl propionate. Using low-boiling-point aliphatic esters can not only dissolve crude p-dioxanone well, but also facilitate its removal in step (5).

[0010] The preferred low-boiling-point liquid alkane mentioned in step (2) is at least one of C5-C7 alkanes. Using low-boiling-point liquid alkane can reduce the solubility of dioxane in low-boiling-point aliphatic ester solvents, which facilitates the precipitation of dioxane products. In addition, the lower boiling point is beneficial for its removal in step (5).

[0011] In the preferred step (2), the mass ratio of aliphatic ester, liquid alkane, and crude p-dioxanone is 0.4~0.8:0.2~0.5:1, and the mass ratio of seed crystal to crude p-dioxanone is 0.001~0.005:1. When the mass ratio of aliphatic ester, liquid alkane, and crude p-dioxanone does not meet the preferred conditions, it is not conducive to the dissolution and precipitation of crude p-dioxanone, nor to the removal of impurities from crude p-dioxanone. When the mass ratio of seed crystal to crude p-dioxanone does not meet the preferred conditions, it is not conducive to obtaining high-purity p-dioxanone crystals during the crystallization process.

[0012] In the preferred step (2), the temperature of the first isothermal crystallization is 5~13℃ and the isothermal crystallization time is 1~4h. When the conditions of the first isothermal crystallization do not meet the preferred conditions, it is not conducive to obtaining high-purity p-dioxanone crystals at a high rate during the first isothermal crystallization process.

[0013] In the preferred step (3), the cooling rate of the crystallization liquid is 1~5℃ / h. When the cooling rate of the crystallization liquid does not meet the preferred conditions, it is not conducive to obtaining high-purity p-dioxanone crystals at a high rate.

[0014] In the preferred step (3), the secondary isothermal crystallization temperature is -10~-5℃ and the isothermal crystallization time is 0.5~3h. When the secondary isothermal crystallization conditions do not meet the preferred conditions, it is not conducive to obtaining high-purity p-dioxanone crystals at a high rate during the secondary isothermal crystallization process.

[0015] In the preferred step (4), the cooling temperature of the crystal and the aliphatic ester is -20~-13℃. The preferred cooling temperature of the crystal and the aliphatic ester is lower than the crystallization temperature of p-dioxanone in step (3), which can avoid the large loss of p-dioxanone crystals during the process of cleaning p-dioxanone crystals with aliphatic esters and improve the yield of p-dioxanone products.

[0016] In the preferred step (4), the mass ratio of aliphatic ester to p-dioxanone crystal is 0.1:1 to 0.3:1. The preferred mass ratio of aliphatic ester to p-dioxanone crystal can ensure that impurities on the surface of p-dioxanone crystal can be effectively removed during the cleaning process of p-dioxanone crystal with low-temperature aliphatic ester, thereby improving the purity of p-dioxanone crystal.

[0017] In the preferred step (5), the temperature of vacuum distillation is 60~90℃, the vacuum degree is 5~30mbar, and the distillation time is 3~6h. The preferred vacuum distillation conditions can effectively remove the aliphatic esters adsorbed on the surface of p-dioxanone crystals and obtain p-dioxanone products with a purity greater than 99.9%.

[0018] 1. First, seed crystals for recrystallization are obtained by vacuum separation and sweating separation of crude p-dioxanone. The purity of the seed crystals is greater than 99.8%. The introduction of high-purity seed crystals is beneficial for inducing the growth of high-purity p-dioxanone crystals on the seed crystal surface in the solvent during recrystallization. Then, the seed crystals are added to a mixture of aliphatic esters, low-boiling-point liquid alkanes, and crude p-dioxanone for recrystallization. P-dioxanone has good solubility in aliphatic esters but poor solubility in liquid alkanes. By adjusting the mixing ratio of the two solvents, the solubility of p-dioxanone in the mixed solvent can be changed, thereby changing the amount and temperature of p-dioxanone crystals precipitated during recrystallization, thus obtaining a high-yield and high-purity p-dioxanone product. The use of a low-boiling-point solvent facilitates solvent removal during subsequent vacuum distillation. By using a low-temperature aliphatic ester to clean the p-dioxanone crystals, the significant loss of p-dioxanone crystals during the cleaning process can be avoided, thus improving the yield of p-dioxanone product. Finally, by performing a single vacuum distillation on the p-dioxanone crystals after low-temperature cleaning, a high-purity p-dioxanone product can be obtained.

[0019] 2. The present invention provides a method for recrystallizing dioxane, which has excellent purification effect and yield of dioxane. The purity of dioxane in the purified product is greater than 99.9%, and the mass yield is greater than 60%. The present invention is simple to operate, and produces high purity and high yield of dioxane. Detailed Implementation

[0020] The present invention will be further illustrated by the following embodiments, but it should be noted that the following embodiments are only used to further illustrate the content of the invention and do not constitute a limitation on the scope of protection of the present invention.

[0021] The raw material p-dioxanone (PDO) used in the following examples is crude p-dioxanone prepared by the distillation section of the applicant (China Petrochemical Yangzi Petrochemical Co., Ltd.).

[0022] The PDO purity determination method used in this example is gas chromatography, and the specific conditions are as follows: Chromatographic conditions and system suitability test: Agilent DB-FFAP capillary column (30m×0.25mm×25μm); carrier gas: nitrogen; inlet temperature: 250℃; detector temperature: 300℃; split ratio: 50:1; temperature program: initial column temperature 80℃, hold for 5 min, temperature ramp rate 20℃ / min, ramp to 230℃, hold for 10 min.

[0023] Test sample: Accurately measure 0.5 mL of PDO sample, add 1.0 mL of hexafluoroisopropanol, and shake well to obtain the test sample.

[0024] Assay: Prepare one sample solution, accurately measure 1 μL, and inject it into the gas chromatograph. Determine the results using the area normalization method. Example 1

[0025] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 98.2%, was added to a 100mL round-bottom flask. The flask was evacuated at 20℃ with a vacuum degree of 50mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 27℃ under normal pressure for sweating. The sweating time was 1.5h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.81%.

[0026] (2) Mix 40g of methyl formate, 20g of n-pentane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl formate: n-pentane: p-dioxanone = 0.4:0.2:1. After cooling the mixture to 13°C, add 0.1g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.001:1. Crystallize at a constant temperature for 4h.

[0027] (3) The crystallization solution was slowly cooled to -5℃ at a cooling rate of 1℃ / h, and crystallized at a constant temperature for 3h to separate 70g of p-dioxanone crystals. The p-dioxanone crystals and methyl formate were cooled to -13℃, and the p-dioxanone crystals were washed with 7g of methyl formate. The mass ratio of methyl formate to p-dioxanone crystals was 0.1:1.

[0028] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 60°C with a vacuum of 30 mbar for 6 hours to obtain 60.2 g of p-dioxanone product, including 0.1 g of seed crystals.

[0029] The purity of dioxane in the tested product was 99.93%. The calculated yield of dioxane product from the entire recrystallization process was 60.1%, excluding the amount of seed crystals. Example 2

[0030] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.7%, was added to a 100mL round-bottom flask. The flask was evacuated at 26℃ with a vacuum degree of 10mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 32℃ under normal pressure for sweating. The sweating time was 0.5h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.91%.

[0031] (2) Mix 80g of methyl propionate, 50g of n-heptane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl propionate: n-heptane: p-dioxanone = 0.8:0.5:1. After cooling the mixture to 5°C, add 0.5g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.005:1. Crystallize at a constant temperature for 1h.

[0032] (3) The crystallization solution was slowly cooled to -10℃ at a cooling rate of 5℃ / h, and crystallized at this temperature for 0.5h to separate 80g of p-dioxanone crystals. The p-dioxanone crystals and methyl propionate were cooled to -20℃, and the p-dioxanone crystals were washed with 24g of methyl propionate. The mass ratio of methyl propionate to p-dioxanone crystals was 0.3:1.

[0033] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 90°C with a vacuum of 5 mbar for 3 hours to obtain 67.7 g of p-dioxanone product, including 0.5 g of seed crystals.

[0034] The purity of dioxane in the tested product was 99.96%. The calculated yield of dioxane product from the entire recrystallization process was 67.2%, excluding the amount of seed crystals. Example 3

[0035] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.3%, was added to a 100mL round-bottom flask. The flask was evacuated at 24℃ with a vacuum degree of 20mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 28℃ under normal pressure for sweating for 1h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.85%.

[0036] (1) Mix 62.5g of methyl acetate, 37.5g of n-hexane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl acetate: n-hexane: p-dioxanone = 0.625: 0.375: 1. After cooling the mixture to 8°C, add 0.2g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.002: 1. Crystallize at a constant temperature for 3h.

[0037] (3) The crystallization solution was slowly cooled to -8℃ at a cooling rate of 2℃ / h, and crystallized at this temperature for 1h to separate 75.2g of p-dioxanone crystals. The p-dioxanone crystals and methyl acetate were cooled to -16℃, and the p-dioxanone crystals were washed with 11.28g of methyl acetate. The mass ratio of methyl acetate to p-dioxanone crystals was 0.15:1.

[0038] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 80°C with a vacuum of 8 mbar for 4 hours to obtain 64.5 g of p-dioxanone product, including 0.2 g of seed crystals.

[0039] The purity of dioxane in the tested product was 99.94%. The calculated yield of dioxane product from the entire recrystallization process was 64.3%, excluding the amount of seed crystals. Example 4

[0040] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.3%, was added to a 100mL round-bottom flask. The flask was evacuated at 24℃ with a vacuum degree of 20mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 28℃ under normal pressure for sweating for 1h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.85%.

[0041] (2) Mix 30g of methyl formate, 32.5g of methyl acetate, 20g of n-pentane, 17.5g of n-hexane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is (methyl formate + methyl acetate): (n-pentane + n-hexane): p-dioxanone = 0.625: 0.375: 1. After cooling the mixture to 8°C, add 0.2g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.002: 1. Crystallize at a constant temperature for 3h.

[0042] (3) The crystallization solution was slowly cooled to -8℃ at a cooling rate of 2℃ / h, and crystallized at this temperature for 1h to separate 74.7g of p-dioxanone crystals. The p-dioxanone crystals, methyl formate, and methyl acetate were cooled to -16℃, and the p-dioxanone crystals were washed with a mixture of 5g of methyl formate and 6.205g of methyl acetate. The mass ratio of the mixture to the p-dioxanone crystals was 0.15:1.

[0043] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 80°C with a vacuum of 8 mbar for 4 hours to obtain 63.0 g of p-dioxanone product, including 0.2 g of seed crystals.

[0044] The purity of dioxane in the tested product was 99.93%. The calculated yield of dioxane product from the entire recrystallization process was 62.8%, excluding the amount of seed crystals. Example 5

[0045] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.6%, was added to a 100mL round-bottom flask. The flask was evacuated at 24℃ with a vacuum degree of 20mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 28℃ under normal pressure for sweating for 1h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.93%.

[0046] (2) Mix 62.5g of methyl acetate, 37.5g of n-hexane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl acetate: n-hexane: p-dioxanone = 0.625: 0.375: 1. After cooling the mixture to 8°C, add 0.2g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.002: 1. Crystallize at a constant temperature for 3h.

[0047] (3) The crystallization solution was slowly cooled to -8℃ at a cooling rate of 2℃ / h, and crystallized at this temperature for 1h to separate 75.4g of p-dioxanone crystals. The p-dioxanone crystals and methyl acetate were cooled to -16℃, and the p-dioxanone crystals were washed with 11.31g of methyl acetate. The mass ratio of methyl acetate to p-dioxanone crystals was 0.15:1.

[0048] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 80°C with a vacuum of 8 mbar for 4 hours to obtain 65.3 g of p-dioxanone product, including 0.2 g of seed crystals.

[0049] The purity of dioxane in the tested product was 99.96%. The calculated yield of dioxane product from the entire recrystallization process was 65.1%, excluding the amount of seed crystals. Example 6

[0050] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.3%, was added to a 100mL round-bottom flask. The flask was evacuated at 24℃ with a vacuum degree of 20mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 28℃ under normal pressure for sweating for 1h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.85%.

[0051] (2) Mix 62.5g of methyl acetate, 20.1g of n-hexane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl acetate: n-hexane: p-dioxanone = 0.625: 0.201: 1. After cooling the mixture to 8°C, add 0.2g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.002: 1. Crystallize at a constant temperature for 3h.

[0052] (3) The crystallization solution was slowly cooled to -8℃ at a cooling rate of 2℃ / h, and crystallized at this temperature for 1h to separate 73.6g of p-dioxanone crystals. The p-dioxanone crystals and methyl acetate were cooled to -16℃, and the p-dioxanone crystals were washed with 11.04g of methyl acetate. The mass ratio of methyl acetate to p-dioxanone crystals was 0.15:1.

[0053] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 80°C with a vacuum of 8 mbar for 4 hours to obtain 62.8 g of p-dioxanone product, including 0.2 g of seed crystals.

[0054] The purity of dioxane in the tested product was 99.92%. The calculated yield of dioxane product from the entire recrystallization process was 62.6%, excluding the amount of seed crystals. Example 7

[0055] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.3%, was added to a 100mL round-bottom flask. The flask was evacuated at 24℃ with a vacuum degree of 20mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 28℃ under normal pressure for sweating for 1h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.85%.

[0056] (2) Mix 62.5g of methyl acetate, 37.5g of n-hexane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl acetate: n-hexane: p-dioxanone = 0.625: 0.375: 1. After cooling the mixture to 12°C, add 0.2g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.002: 1. Crystallize at a constant temperature for 3h.

[0057] (3) The crystallization solution was slowly cooled to -8℃ at a cooling rate of 2℃ / h, and crystallized at this temperature for 1h to separate 72.3g of p-dioxanone crystals. The p-dioxanone crystals and methyl acetate were cooled to -16℃, and the p-dioxanone crystals were washed with 10.845g of methyl acetate. The mass ratio of methyl acetate to p-dioxanone crystals was 0.15:1.

[0058] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 80°C with a vacuum of 8 mbar for 4 hours to obtain 62.9 g of p-dioxanone product, including 0.2 g of seed crystals.

[0059] The purity of dioxane in the tested product was 99.96%. The calculated yield of dioxane product from the entire recrystallization process was 62.7%, excluding the amount of seed crystals. Example 8

[0060] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.3%, was added to a 100mL round-bottom flask. The flask was evacuated at 24℃ with a vacuum degree of 20mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 28℃ under normal pressure for sweating for 1h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.85%.

[0061] (2) Mix 62.5g of methyl acetate, 37.5g of n-hexane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl acetate: n-hexane: p-dioxanone = 0.625: 0.375: 1. After cooling the mixture to 5°C, add 0.2g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.002: 1. Crystallize at a constant temperature for 3h.

[0062] (3) The crystallization solution was slowly cooled to -8℃ at a cooling rate of 2℃ / h, and crystallized at this temperature for 1h to separate 77.3g of p-dioxanone crystals. The p-dioxanone crystals and methyl acetate were cooled to -16℃, and the p-dioxanone crystals were washed with 11.595g of methyl acetate. The mass ratio of methyl acetate to p-dioxanone crystals was 0.15:1.

[0063] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 80°C with a vacuum of 8 mbar for 4 hours to obtain 66.5 g of p-dioxanone product, including 0.2 g of seed crystals.

[0064] The purity of dioxane in the tested product was 99.91%. The calculated yield of dioxane product from the entire recrystallization process was 66.3%, excluding the amount of seed crystals. Example 9

[0065] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.3%, was added to a 100mL round-bottom flask. The flask was evacuated at 24℃ with a vacuum degree of 20mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 28℃ under normal pressure for sweating for 1h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.85%.

[0066] (2) Mix 62.5g of methyl acetate, 37.5g of n-hexane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl acetate: n-hexane: p-dioxanone = 0.625: 0.375: 1. After cooling the mixture to 8°C, add 0.2g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.002: 1. Crystallize at a constant temperature for 3h.

[0067] (3) The crystallization solution was slowly cooled to -8℃ at a cooling rate of 2℃ / h, and crystallized at this temperature for 1h to separate 75.2g of p-dioxanone crystals. The p-dioxanone crystals and methyl acetate were cooled to -13℃, and the p-dioxanone crystals were washed with 11.28g of methyl acetate. The mass ratio of methyl acetate to p-dioxanone crystals was 0.15:1.

[0068] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 80°C with a vacuum of 8 mbar for 4 hours to obtain 62.5 g of p-dioxanone product, including 0.2 g of seed crystals.

[0069] The purity of dioxane in the tested product was 99.95%. The calculated yield of dioxane product from the entire recrystallization process was 62.3%, excluding the amount of seed crystals. Example 10

[0070] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.3%, was added to a 100mL round-bottom flask. The flask was evacuated at 24℃ with a vacuum degree of 20mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 28℃ under normal pressure for sweating for 1h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.85%.

[0071] (2) Mix 62.5g of methyl acetate, 37.5g of n-hexane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl acetate: n-hexane: p-dioxanone = 0.625: 0.375: 1. After cooling the mixture to 8°C, add 0.2g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.002: 1. Crystallize at a constant temperature for 3h.

[0072] (3) The crystallization solution was slowly cooled to -8℃ at a cooling rate of 2℃ / h, and crystallized at this temperature for 1h to separate 75.2g of p-dioxanone crystals. The p-dioxanone crystals and methyl acetate were cooled to -19℃, and the p-dioxanone crystals were washed with 11.28g of methyl acetate. The mass ratio of methyl acetate to p-dioxanone crystals was 0.15:1.

[0073] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 80°C with a vacuum of 8 mbar for 4 hours to obtain 66.3 g of p-dioxanone product, including 0.2 g of seed crystals.

[0074] The purity of dioxane in the tested product was 99.92%. The calculated yield of dioxane product from the entire recrystallization process was 66.1%, excluding the amount of seed crystals. Example 11

[0075] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.3%, was added to a 100mL round-bottom flask. The flask was evacuated at 24℃ with a vacuum degree of 20mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 28℃ under normal pressure for sweating for 1h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.85%.

[0076] (2) Mix 62.5g of methyl acetate, 37.5g of n-hexane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl acetate: n-hexane: p-dioxanone = 0.625: 0.375: 1. After cooling the mixture to 8°C, add 0.2g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.002: 1. Crystallize at a constant temperature for 3h.

[0077] (3) The crystallization solution was slowly cooled to -4℃ at a cooling rate of 2℃ / h, and crystallized at this temperature for 1h to separate 71.4g of p-dioxanone crystals. The p-dioxanone crystals and methyl acetate were cooled to -16℃, and the p-dioxanone crystals were washed with 10.71g of methyl acetate. The mass ratio of methyl acetate to p-dioxanone crystals was 0.15:1.

[0078] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 80°C with a vacuum of 8 mbar for 4 hours to obtain 61.6 g of p-dioxanone product, including 0.2 g of seed crystals.

[0079] The purity of dioxane in the tested product was 99.95%. The calculated yield of dioxane product from the entire recrystallization process was 61.4%, excluding the amount of seed crystals. Example 12

[0080] (1) 20g of p-dioxanone product obtained from the distillation section, with a p-dioxanone purity of 99.3%, was added to a 100mL round-bottom flask. The flask was evacuated at 24℃ with a vacuum degree of 20mbar to obtain a mixture of p-dioxanone crystals and liquid. The p-dioxanone crystals were separated and heated to 28℃ under normal pressure for sweating for 1h. The p-dioxanone crystals were separated again as seed crystals for recrystallization. The p-dioxanone purity of the seed crystals was 99.85%.

[0081] (2) Mix 62.5g of methyl acetate, 37.5g of n-hexane and 100g of p-dioxanone obtained from the distillation section. The mass ratio of each substance in the mixture is methyl acetate: n-hexane: p-dioxanone = 0.625: 0.375: 1. After cooling the mixture to 8°C, add 0.2g of the prepared seed crystals. The mass ratio of the seed crystals to p-dioxanone is 0.002: 1. Crystallize at a constant temperature for 3h.

[0082] (3) The crystallization solution was slowly cooled to -19℃ at a cooling rate of 2℃ / h, and crystallized at this temperature for 1h to separate 78.3g of p-dioxanone crystals. The p-dioxanone crystals and methyl acetate were cooled to -16℃, and the p-dioxanone crystals were washed with 11.745g of methyl acetate. The mass ratio of methyl acetate to p-dioxanone crystals was 0.15:1.

[0083] (4) The cleaned p-dioxanone crystals were distilled under reduced pressure at 80°C with a vacuum of 8 mbar for 4 hours to obtain 68.3 g of p-dioxanone product, including 0.2 g of seed crystals.

[0084] The purity of dioxane in the tested product was 99.91%. The calculated yield of dioxane product from the entire recrystallization process was 68.1%, excluding the amount of seed crystals.

[0085] The effects of crystallization temperature and washing temperature on product purity and product yield in Examples 7-12 were compared and analyzed. The results are shown in Table 1 below.

[0086]

[0087] Comparing Examples 9 and 10, it can be seen that, under the same conditions, a lower washing temperature results in lower product purity and higher product yield. Comparing Examples 7 and 8, and Examples 11 and 12, it can be seen that, under the same conditions, a lower crystallization temperature results in more dioxanone crystals separated by recrystallization, higher product yield, and lower product purity. Comparing Examples 9 and 11, and Examples 7 and 9, it can be seen that, under the same conditions, product purity and product yield are affected by both crystallization temperature and washing temperature.

[0088] The crystallization temperature determines the solubility of p-dioxanone in the solvent. A higher crystallization temperature results in greater solubility, less p-dioxanone crystals, a lower crystallization rate, and higher crystal purity. Conversely, a lower crystallization temperature results in lower solubility, more p-dioxanone crystals, a higher crystallization rate, and lower crystal purity. The cleaning temperature determines the solubility of p-dioxanone in the cleaning agent. A higher cleaning temperature results in greater solubility, greater crystal loss during cleaning, deeper cleaning, and higher crystal purity. Conversely, a lower cleaning temperature results in lower solubility, less crystal loss during cleaning, shallower cleaning, and lower crystal purity. The crystallization and cleaning temperatures work synergistically to affect product purity and yield.

Claims

1. A method for recrystallizing p-dioxanone, characterized in that, Includes the following steps: (1) Vacuum the crude p-dioxanone product at a certain temperature to obtain a mixture of p-dioxanone crystals and liquid. Heat the separated p-dioxanone crystals to a certain temperature under normal pressure to sweat, and separate the p-dioxanone crystals again as seed crystals for recrystallization. (2) Mix low-boiling-point aliphatic esters, low-boiling-point liquid alkanes and crude p-dioxanone in proportion. After cooling the mixture to a certain temperature, add the seed crystals prepared in step (1) and carry out a constant-temperature crystallization. (3) The crystallization solution from step (2) is slowly cooled to a certain temperature and subjected to secondary isothermal crystallization, and then the p-dioxanone crystals are separated. (4) Cool the p-dioxanone crystals separated in step (3) and the aliphatic esters mentioned in step (2) to a certain temperature, and clean the p-dioxanone crystals with low-temperature aliphatic esters. (5) The cleaned p-dioxanone crystals were distilled under reduced pressure to obtain a high-purity p-dioxanone product.

2. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (1), the purity of crude dioxane is 98.2-99.7%.

3. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (1), the vacuum temperature is 20~26℃ and the vacuum degree is 10~50mbar.

4. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (1), the sweating temperature is 27~32℃ and the sweating time is 0.5~1.5h.

5. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (2), the low-boiling-point aliphatic ester is at least one of methyl formate, ethyl formate, propyl formate, methyl acetate, ethyl acetate, and methyl propionate.

6. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (2), the low-boiling-point liquid alkane is at least one of C5 to C7 alkane.

7. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (2), the mass ratio of aliphatic ester, liquid alkane, and crude p-dioxanone is 0.4~0.8:0.2~0.5:1, and the mass ratio of seed crystals to crude p-dioxanone is 0.001~0.005:

1.

8. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (2), the temperature for one isothermal crystallization is 5~13℃, and the isothermal crystallization time is 1~4h.

9. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (3), the cooling rate of the crystallization solution is 1~5℃ / h.

10. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (3), the secondary isothermal crystallization temperature is -10~-5℃, and the isothermal crystallization time is 0.5~3h.

11. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (4), the cooling temperature of the crystals and aliphatic esters is -20~-13℃.

12. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (4), the mass ratio of aliphatic ester to p-dioxanone crystals is 0.1~0.3:

1.

13. The method for recrystallizing p-dioxanone according to claim 1, characterized in that: In step (5), the temperature of vacuum distillation is 60~90℃, the vacuum degree is 5~30mbar, and the distillation time is 3~6h.

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