CN114149403A - Mixed crystal form glycolide, and preparation method and application thereof - Google Patents
Mixed crystal form glycolide, and preparation method and application thereof Download PDFInfo
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- CN114149403A CN114149403A CN202111361014.2A CN202111361014A CN114149403A CN 114149403 A CN114149403 A CN 114149403A CN 202111361014 A CN202111361014 A CN 202111361014A CN 114149403 A CN114149403 A CN 114149403A
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- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 title claims abstract description 125
- 239000013078 crystal Substances 0.000 title claims abstract description 74
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 239000000706 filtrate Substances 0.000 claims abstract description 51
- 238000001914 filtration Methods 0.000 claims abstract description 51
- 239000002245 particle Substances 0.000 claims abstract description 42
- 239000002904 solvent Substances 0.000 claims abstract description 33
- 238000001953 recrystallisation Methods 0.000 claims abstract description 28
- 238000003756 stirring Methods 0.000 claims abstract description 25
- 239000012535 impurity Substances 0.000 claims abstract description 22
- 239000003599 detergent Substances 0.000 claims abstract description 21
- 238000001816 cooling Methods 0.000 claims abstract description 17
- 238000001035 drying Methods 0.000 claims abstract description 17
- 239000005457 ice water Substances 0.000 claims abstract description 17
- 238000000746 purification Methods 0.000 claims abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 45
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 30
- 229920000954 Polyglycolide Polymers 0.000 claims description 20
- 239000004633 polyglycolic acid Substances 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 14
- 239000003054 catalyst Substances 0.000 claims description 12
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 claims description 12
- 238000007151 ring opening polymerisation reaction Methods 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000002425 crystallisation Methods 0.000 claims description 6
- 230000008025 crystallization Effects 0.000 claims description 6
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 238000002441 X-ray diffraction Methods 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- 238000006116 polymerization reaction Methods 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 21
- 239000000047 product Substances 0.000 description 18
- 230000000052 comparative effect Effects 0.000 description 12
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000007670 refining Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZPLCXHWYPWVJDL-UHFFFAOYSA-N 4-[(4-hydroxyphenyl)methyl]-1,3-oxazolidin-2-one Chemical compound C1=CC(O)=CC=C1CC1NC(=O)OC1 ZPLCXHWYPWVJDL-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 238000006068 polycondensation reaction Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/12—1,4-Dioxanes; Hydrogenated 1,4-dioxanes not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Polyesters Or Polycarbonates (AREA)
Abstract
The invention discloses a mixed crystal form glycolide and a preparation method thereof, which solve the problem that the stability, the polymerization and the safety of the prior glycolide are to be further improved, and comprise the following steps: (1) dissolving crude glycolide in a solvent at a ratio of 1-3 g/ml at 60-90 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow platelets; (2) and (2) under the condition of stirring, adding the light yellow platelet obtained in the step (1) into a detergent according to the proportion of 1-3 g/ml to obtain a solution containing white particles, and filtering and drying to obtain the mixed crystal form glycolide. The glycolide has a mixed crystal form, and has the advantages of good stability, polymerizability and safety, simple and convenient preparation method, easy implementation, low cost, small solvent consumption, short purification process and recoverable solvent.
Description
Technical scheme
The invention belongs to the technical field of glycolide production, and particularly relates to a mixed crystal form glycolide and a preparation method and application thereof.
Background
Glycolide is a key monomer for the preparation of high molecular weight polyglycolic acid. In general, the synthesis of glycolide is divided into two steps: firstly, low molecular weight polyglycolic acid is synthesized through esterification polycondensation of glycolic acid; secondly, the low molecular weight polyglycolic acid is subjected to high-temperature depolymerization/solvent azeotropy to obtain a product, namely crude glycolide. However, crude glycolide contains various impurities such as water, glycolic acid, and low-molecular-weight polyglycolic acid, and is disadvantageous for the production of high-molecular-weight polyglycolic acid. Therefore, the crude glycolide needs to be purified to meet the polymerization requirement.
The crude glycolide can be purified by solvent extraction, rectification, recrystallization, etc. CN1056689A is used for separating crude glycolide from other impurities as vapor component in gas flow and recovering cyclic ester solvent in the gas flow, and the method has complicated separation process and low yield. US4650851 dissolves the crude glycolide in dichloromethane, mixes with neutral alumina, stirs and filters, and this process is complicated and difficult to industrialize, and the reduction of acid impurity content and the mixing and stirring time are greatly related and difficult to control. CN104619690A introduces crude glycolide and other distillates with volatile components into a rectifier, rectifies the distillate through gas-liquid countercurrent contact, cools and recovers the glycolide, but in the method, a high boiling point organic solvent and a solubilizer are used for depolymerization, and the glycolide separated by the rectifier still contains a small amount of impurities and organic solvents and needs further refining treatment. Recrystallization is a common method for refining crude glycolide, and CN100999516, CN101054371 and the like report a method for performing multiple recrystallization on crude glycolide by using an organic solvent such as ethyl acetate, but the attention points are that the influence of the recrystallization process on the yield of the glycolide is basically ignored, and the influence on the crystal form of the glycolide is ignored. In fact, glycolide belongs to a molecular crystal, and a crystal transformation phenomenon is easy to occur. In the purification process of glycolide, the change of conditions such as solvent, temperature and the like can cause the crystal form of the glycolide to be transformed, thereby influencing the stability, the polymerization, the safety and the like of the glycolide. Therefore, in the refining process of crude glycolide, the crystal structure and control of glycolide become problems to be solved urgently.
Disclosure of Invention
The invention aims to solve the technical problems and provide mixed crystal glycolide which can be used as a seed crystal for purifying crude glycolide by recrystallization and crude glycolide by melt crystallization and can be directly subjected to ring-opening polymerization to prepare polyglycolic acid without adding a catalyst.
The invention also aims to provide a preparation method of the mixed crystal form glycolide, which has the advantages of simple and convenient preparation method, easy implementation, low cost, small solvent consumption, short purification process and recoverable solvent.
The invention also provides an application of the mixed crystal form glycolide.
The preparation method of the mixed crystal form glycolide comprises the following steps:
(1) dissolving crude glycolide in a solvent at a ratio of 1-3 g/ml at 60-90 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow platelets;
(2) and (2) under the condition of stirring, adding the light yellow platelet obtained in the step (1) into a detergent according to the proportion of 1-3 g/ml to obtain a solution containing white particles, and filtering and drying to obtain the mixed crystal form glycolide.
In the step (1), the solvent is at least one of acetone, butanone, petroleum ether, n-hexane, cyclohexane, ethyl acetate and butyl acetate. Preferably, the solvent is ethyl acetate or butyl acetate. The solubility of glycolide in ethyl acetate or butyl acetate is higher, which is beneficial to the recrystallization process. The ratio of the mass of the crude glycolide to the volume of the solvent is 1-3 g/ml. The concentration of the crude glycolide is higher than the range, the dissolution is incomplete, and the final yield is influenced; the concentration of the crude glycolide is lower than the range, and the solvent is excessive, so that the recrystallization process is not facilitated.
In the step (2), the detergent is at least one of ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-pentanol and isoamyl alcohol. Preferably, the solvent is isopropanol or isoamyl alcohol. On one hand, isopropanol or isoamylol with strong polarity easily forms hydrogen bonds with acid substances such as glycolic acid in glycolide, and the washing effect is stronger; on the other hand, the strong polar isopropanol or isoamylol has stronger inductivity to the crystal form transformation of the glycolide, and the mixed crystal form glycolide is easier to obtain. The ratio range between the mass of the light yellow platelets obtained in the step (1) and the volume of the detergent is 1-3 g/ml. The concentration is higher than the range, the washing effect is poor, and the purity of the final product is not high; the concentration is lower than the range, the detergent is excessive, and the purity of the product is not obviously improved.
In the step (2), the stirring speed is 50-500 rpm; the stirring time is 15-120 min.
In the step (2), the temperature is controlled to be between room temperature and 90 ℃.
The XRD pattern of the mixed crystal form glycolide simultaneously has a characteristic peak of the crystal form glycolide A and a characteristic peak of the crystal form glycolide B;
characteristic peaks of glycolide in the crystal form A at least appear at 14.9 degrees, 30.2 degrees and 46.1 degrees of 2 theta;
characteristic peaks of the glycolide of the crystal form B at least appear at positions of 2 theta, 16.4 degrees, 18.4 degrees, 21.1 degrees, 26.8 degrees, 31.5 degrees and 37.6 degrees;
wherein the error range of the 2 theta value is +/-0.2 degrees.
Based on the total mass of glycolide, the content of glycolide in the crystal form A is 1-99 wt%, and the content of glycolide in the crystal form B is 99-1 wt%.
The mixed crystal form glycolide is used as a seed crystal for recrystallization purification of crude glycolide or melt crystallization purification of crude glycolide.
The addition amount of the mixed crystal glycolide is preferably 0.1-30 wt% (more preferably 1-20 wt%) of the crude glycolide. The addition amount is too low, and the crystallization promoting effect is not good; if the amount is too high, the crystallization is not further promoted.
The mixed crystal form glycolide is directly applied to the preparation of polyglycolic acid by ring-opening polymerization without adding a catalyst. The mixed crystal form can be directly subjected to ring-opening polymerization to prepare polyglycolic acid without adding a catalyst. The B crystal form glycolide is easy to absorb water and hydrolyze into linear dimer glycolic acid, and can catalyze the A crystal form glycolide to spontaneously carry out ring-opening polymerization under certain conditions to prepare polyglycolic acid. The polyglycolic acid product has no catalyst/impurity residue, does not cause harm to human bodies, has the molecular weight of more than 15000g/mol, and can be directly used for absorbable biomedical materials such as surgical sutures and the like.
When used for preparing polyglycolic acid, the mixed crystal glycolide contains at least 1 wt% of B-type glycolide. Preferably, the content of the B-type glycolide is 10-20 wt%. When the content of the B-type glycolide is less than 10 wt%, the catalytic effect is poor, and polyglycolic acid with a higher molecular weight cannot be obtained; when the content of B-type glycolide is more than 20 wt%, the content of dimer formed after hydrolysis becomes excessive, and the catalytic effect is rather suppressed, and polyglycolic acid having a desired molecular weight cannot be obtained.
By adopting the method, the yield of the purified glycolide is more than 80 percent, the acid value content is lower than 2.0 multiplied by 10 < -6 > mol/g, the purity is higher than 99 weight percent, and only one recrystallization and one washing are needed, so that the using amount of the solvent is reduced, the purification process is shortened, and a better technical effect is achieved.
Compared with the prior art, the invention also has the following beneficial effects:
(1) the mixed crystal form glycolide prepared by the invention takes a common solvent as a raw material, the preparation method is simple and easy to implement, has low cost, and the solvent dosage is small, can be recovered, and is beneficial to industrial popularization;
(2) the mixed crystal form glycolide prepared by the invention has a proper crystal form with good stability, polymerization and safety, and can be used as a crystal seed for purifying crude glycolide by recrystallization and crude glycolide by melt crystallization;
(3) the mixed crystal form glycolide prepared by the invention can be directly subjected to ring-opening polymerization to prepare polyglycolic acid without adding a catalyst.
Drawings
Fig. 1 is an XRD pattern of glycolide prepared in comparative example 1, comparative example 2 and example 1.
Detailed Description
The test analysis methods used in the following examples and comparative examples are as follows:
XRD: using a PANalytical X' Pert X-ray diffractometerAnd testing conditions are as follows: CuKαTargeting
The voltage is 40kV, the current is 30mA, the scanning range is 5.0-40.0 degrees, the step width is 0.02 degree, and the scanning speed is 5 degrees/min.
Chemical purity:
i. liquid chromatography conditions:
a chromatographic column: c18 column, 5um, 250mm × 4.6 mm;
mobile phase: pure acetonitrile;
sample introduction amount: 20 uL;
flow rate: 0.8/min;
an ultraviolet detector: the ultraviolet detection wavelength is 214 nm;
column temperature: at 30 ℃.
Test method:
0.1012g of glycolide is accurately weighed, added into a 50ml volumetric flask containing a certain amount of mobile phase, ultrasonically treated for 30min, diluted to scale, shaken up, filtered by a 0.45um nylon filter membrane and tested. And carrying out sample injection detection according to chromatographic conditions.
Acid value:
dissolving 5g of glycolide in 10ml of dimethyl sulfoxide DMSO, adding 3 drops of bromothymol blue serving as an indicator, titrating with 0.1mol/L of NaOH benzyl alcohol solution, and obtaining the titration end point when the color of the indicator changes from yellow to green and then changes to light blue. The consumed alkali solution was recorded and the acid number content of glycolide was calculated.
The present invention will be described in further detail with reference to specific examples. The following examples are merely illustrative of the present invention, but the present invention is not limited to these examples.
Comparative example 1
(1) Dissolving crude glycolide in an ethyl acetate solvent at a ratio of 2g/ml at 70 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow lamellar crystals;
(2) and (3) repeating the step (1) for 2 times to obtain white platelets.
Comparative example 2
(1) Adding crude glycolide into an isopropanol detergent at a stirring speed of 200rpm and room temperature in a ratio of 2g/ml, stirring for 1h to obtain a solution containing light yellow particles, and filtering and drying to obtain light yellow particles;
(2) repeating the step (1) for 2 times to obtain white particles.
Example 1
(1) Dissolving crude glycolide in an ethyl acetate solvent at a ratio of 2g/ml at 70 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow lamellar crystals;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an isopropanol detergent at room temperature and 200rpm, stirring for 45min to obtain a solution containing white particles, filtering, and drying to obtain the white particles.
Example 2
(1) Dissolving crude glycolide in an acetone solvent at a ratio of 1.5g/ml at 60 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow platelets;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an n-butanol detergent at the ratio of 2.5g/ml at the temperature of 50 ℃ and at the speed of 50rpm, stirring for 1 hour to obtain a solution containing white particles, filtering and drying to obtain the white particles.
Example 3
(1) Dissolving crude glycolide in a butyl acetate solvent at a ratio of 1.5g/ml at 90 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow platelets;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an isoamyl alcohol detergent at the ratio of 2g/ml at the temperature of 70 ℃ and at the speed of 50rpm, stirring for 30min to obtain a solution containing white particles, and filtering and drying to obtain the white particles.
Example 4
(1) Dissolving crude glycolide in an acetone solvent at a ratio of 1g/ml at 70 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow lamellar crystals;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an n-butanol detergent at the ratio of 3g/ml at the temperature of 60 ℃ and the speed of 100rpm, stirring for 1h to obtain a solution containing white particles, filtering and drying to obtain the white particles.
Example 5
(1) Dissolving crude glycolide in a butyl acetate solvent at a ratio of 3g/ml at 80 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow platelets;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an isoamyl alcohol detergent at the room temperature and under the condition of 150rpm, stirring for 30min to obtain a solution containing white particles, and filtering and drying to obtain the white particles.
TABLE 1 index of purified products
Application comparative example 1
(1) Dissolving crude glycolide in an ethyl acetate solvent at a ratio of 2g/ml at 70 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow lamellar crystals;
(2) and (3) repeating the step (1) for 2 times to obtain white platelets.
(3) And (3) exposing the white platelet in the step (2) for 1 day in an environment with the temperature of 50 ℃ and the relative humidity of 50%, and directly carrying out ring-opening polymerization reaction for 1h at the temperature of 200 ℃ and the absolute pressure of 50Pa (absolute pressure) under the condition of not adding any catalyst to obtain the product.
The product is still glycolide, i.e. no polymerization reaction occurs.
Comparative application example 2
(1) Adding crude glycolide into an isopropanol detergent at a stirring speed of 200rpm and room temperature in a ratio of 2g/ml, stirring for 1h to obtain a solution containing light yellow particles, and filtering and drying to obtain light yellow particles;
(2) repeating the step (1) for 2 times to obtain white particles.
(3) And (3) exposing the white particles in the step (2) for 1 day in an environment with the temperature of 50 ℃ and the relative humidity of 50%, and directly carrying out ring-opening polymerization reaction for 1h at the temperature of 200 ℃ and the absolute pressure of 50Pa (without adding any catalyst) to obtain the product.
The detection proves that the product is polyglycolic acid, but the molecular weight is low, and is only about 5000 g/mol.
Comparative application example 3
(1) Dissolving crude glycolide in an ethyl acetate solvent at room temperature in a ratio of 1.3g/ml, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow platelets;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an isopropanol detergent at room temperature and 200rpm, stirring for 30min to obtain a solution containing white particles, filtering, and drying to obtain the white particles.
(3) And (3) exposing the white platelet in the step (2) for 1 day in an environment with the temperature of 50 ℃ and the relative humidity of 50%, and directly carrying out ring-opening polymerization reaction for 1h at the temperature of 200 ℃ and the absolute pressure of 50Pa (absolute pressure) under the condition of not adding any catalyst to obtain the product.
Detecting that the white particles obtained in the step (2) contain 8 wt% of glycolide in crystal form B; the product obtained in the step (3) is polyglycolic acid, and has a low molecular weight of only about 6000 g/mol.
Application comparative example 4
(1) Dissolving crude glycolide in an ethyl acetate solvent at a ratio of 2.5g/ml at room temperature to obtain a solution, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow platelets;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an isopropanol detergent at the temperature of 50 ℃ and the rpm of 100, stirring for 60min to obtain a solution containing white particles, filtering and drying to obtain the white particles.
(3) And (3) exposing the white platelet in the step (2) for 1 day in an environment with the temperature of 50 ℃ and the relative humidity of 50%, and directly carrying out ring-opening polymerization reaction for 1h at the temperature of 200 ℃ and the absolute pressure of 50Pa (absolute pressure) under the condition of not adding any catalyst to obtain the product.
Detecting that the white particles obtained in the step (2) contain 23 wt% of glycolide in the crystal form B; the product obtained in the step (3) is polyglycolic acid, and has a low molecular weight of only about 8000 g/mol.
Application example 1
(1) Dissolving crude glycolide in an ethyl acetate solvent at a ratio of 2g/ml at 70 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow lamellar crystals;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an isopropanol detergent at the temperature of 30 ℃ and the rpm of 200, stirring for 45min to obtain a solution containing white particles, filtering and drying to obtain the white particles.
(3) And (3) exposing the white platelet in the step (2) for 1 day in an environment with the temperature of 50 ℃ and the relative humidity of 50%, and directly carrying out ring-opening polymerization reaction for 1h at the temperature of 200 ℃ and the absolute pressure of 50Pa (absolute pressure) under the condition of not adding any catalyst to obtain the product.
Detecting that the white particles obtained in the step (2) contain 13 wt% of glycolide in crystal form B; the product obtained in the step (3) is polyglycolic acid with high molecular weight of about 15000 g/mol.
Application example 2
(1) Dissolving crude glycolide in an ethyl acetate solvent at a ratio of 2.5g/ml at 90 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow platelets;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an isopropanol detergent at the ratio of 1g/ml at the temperature of 40 ℃ and the rpm of 400, stirring for 120min to obtain a solution containing white particles, filtering and drying to obtain the white particles.
(3) And (3) exposing the white particles in the step (2) for 2 days in an environment with the temperature of 70 ℃ and the relative humidity of 60%, and directly carrying out ring-opening polymerization reaction for 1h at the temperature of 180 ℃ and under the absolute pressure of 50Pa (without adding any catalyst) to obtain the product.
Detecting that the white particles obtained in the step (2) contain 18 wt% of glycolide in the crystal form B; the product obtained in the step (3) is polyglycolic acid with high molecular weight of about 30000 g/mol.
Application example 3
(1) Dissolving crude glycolide in an ethyl acetate solvent at a ratio of 2.5g/ml at 90 ℃, adding 5 wt% of the white particles prepared in the example 1 into the solution, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow lamellar crystals;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an isopropanol detergent at the room temperature and the speed of 400rpm, stirring for 30min to obtain a solution containing white particles, and filtering and drying to obtain the white particles.
Analysis showed that after 5 wt% of example 1 was added as seed crystal, the yield of glycolide reached 75%, and the purity reached 92%, both of which were significantly higher than those of the product obtained in comparative example 1 (65%) and purity (89%).
Application example 4
(1) Dissolving crude glycolide in an ethyl acetate solvent at a ratio of 2.5g/ml at 90 ℃, adding 10 wt% of the white particles prepared in the example 1 into the solution, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow lamellar crystals;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an isopropanol detergent at the room temperature and the speed of 400rpm, stirring for 30min to obtain a solution containing white particles, and filtering and drying to obtain the white particles.
Analysis showed that the yield of glycolide reached 87% and the purity reached 95% after 10 wt% of example 1 was added as seed, both being significantly higher than the yield (65%) and the purity (89%) of the product obtained in comparative example 1.
Application example 5
(1) Dissolving crude glycolide in an ethyl acetate solvent at a ratio of 2.5g/ml at 90 ℃, adding 25 wt% of the white particles prepared in the example 1 into the solution, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow lamellar crystals;
(2) and (2) adding the light yellow platelet prepared in the step (1) into an isopropanol detergent at the room temperature and the speed of 400rpm, stirring for 30min to obtain a solution containing white particles, and filtering and drying to obtain the white particles.
Analysis showed that after 25 wt% of example 1 was added as seed crystal, the yield of glycolide reached 89% and the purity reached 95%, both being significantly higher than the yield (65%) and purity (89%) of the product obtained in comparative example 1.
Claims (10)
1. A preparation method of mixed crystal glycolide is characterized by comprising the following steps:
(1) dissolving crude glycolide in a solvent at a ratio of 1-3 g/ml at 60-90 ℃, filtering to remove impurities and obtain a filtrate, naturally cooling the filtrate to room temperature, directly placing the filtrate in an ice water bath for recrystallization, and filtering to obtain light yellow platelets;
(2) and (2) under the condition of stirring, adding the light yellow platelet obtained in the step (1) into a detergent according to the proportion of 1-3 g/ml to obtain a solution containing white particles, and filtering and drying to obtain the mixed crystal form glycolide.
2. The method for preparing glycolide in mixed crystal form according to claim 1, wherein in step (1), the solvent is at least one of acetone, butanone, petroleum ether, n-hexane, cyclohexane, ethyl acetate and butyl acetate.
3. The method for preparing glycolide in mixed crystal form according to claim 1, wherein in step (2), the detergent is at least one of ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-pentanol and isoamyl alcohol.
4. The method for preparing glycolide in mixed crystal form according to claim 1 or 3, wherein in the step (2), the stirring rate is 50 to 500 rpm; the stirring time is 15-120 min.
5. The method for preparing glycolide in mixed crystal form according to claim 1 or 3, wherein in the step (2), the temperature is controlled to be in the range of room temperature to 70 ℃.
6. A mixed crystal form glycolide prepared by the preparation method of any one of claims 1 to 5, wherein the mixed crystal form glycolide has an XRD pattern having characteristic peaks of the glycolide crystal form A and characteristic peaks of the glycolide crystal form B;
characteristic peaks of glycolide in the crystal form A at least appear at 14.9 degrees, 30.2 degrees and 46.1 degrees of 2 theta;
characteristic peaks of the glycolide of the crystal form B at least appear at positions of 2 theta, 16.4 degrees, 18.4 degrees, 21.1 degrees, 26.8 degrees, 31.5 degrees and 37.6 degrees;
wherein the error range of the 2 theta value is +/-0.2 degrees.
7. The mixed crystal form glycolide according to claim 6, wherein the content of the glycolide of the crystal form A is 1 to 99 wt% and the content of the glycolide of the crystal form B is 99 to 1 wt% based on the total mass of the glycolide.
8. Use of the glycolide in mixed crystal form according to claim 6 or 7 as a seed crystal for recrystallization purification of crude glycolide or for melt crystallization purification of crude glycolide.
9. The use of glycolide in mixed crystal form according to claim 8, wherein the amount of glycolide in mixed crystal form is 0.1-30 wt% of the crude glycolide.
10. Use of a glycolide in the form of mixed crystals according to claim 8 or 9, characterised in that the glycolide in the form of mixed crystals is directly subjected to ring-opening polymerisation without the addition of a catalyst to produce polyglycolic acid.
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