Method for selenium catalyzed synthesis of polylactic acid
By using a selenium catalyst to directly polymerize L-lactic acid into PLA under metal-free conditions, the problems of metal residue and low yield were solved, and efficient and economical medical-grade polylactic acid production was achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- YANGZHOU UNIV
- Filing Date
- 2024-12-27
- Publication Date
- 2026-06-23
AI Technical Summary
Existing technologies for synthesizing medical-grade polylactic acid (PLA) suffer from issues such as residual tin and low yields in the L-lactide synthesis process, resulting in high costs.
PLA was synthesized directly by the metal-free polymerization of L-lactic acid using a selenium catalyst. By using substituted selenite as a catalyst precursor and controlling the air flow rate and temperature, catalyst deactivation was avoided, and PLA was synthesized directly, skipping the L-lactide synthesis step.
The synthesized polylactic acid is metal-free and requires no washing, which reduces production costs, increases yield, and achieves medical-grade quality.
Smart Images
Figure CN119638966B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of materials chemistry preparation, specifically relating to a method for preparing medical-grade polylactic acid materials. Background Technology
[0002] In the medical field, polylactic acid (PLA) has become an ideal material for innovative medical devices, drug delivery systems, and biodegradable implants due to its excellent biocompatibility and biodegradability. However, producing PLA that meets medical standards faces many significant challenges, among which the control of tin residue is particularly stringent. Currently, PLA is mainly synthesized by the polymerization of L-lactide, which uses a tin catalyst and easily leads to tin residue. Tin removal requires washing, increasing costs. Furthermore, L-lactide is synthesized from L-lactic acid, a process with currently low yields, increasing process costs and generating solid waste. Developing a new method for the direct polymerization of L-lactic acid using non-metallic catalysts to synthesize PLA can solve these problems. Summary of the Invention
[0003] This invention develops a selenium-catalyzed method for the synthesis of polylactic acid (PLA). Utilizing selenium, which has higher biotolerance, as a catalyst, PLA is directly synthesized from L-lactic acid under metal-free conditions. The PLA synthesized by this method does not require washing, thus being metal-free. Furthermore, the direct synthesis of PLA from L-lactic acid bypasses the L-lactide synthesis step, making it more economical.
[0004] The objective of this invention is achieved as follows: a method for the selenium-catalyzed synthesis of polylactic acid, wherein a substitute selenite is added as a catalyst precursor to L-lactic acid at an amount of 0.02–0.08% of the mass of L-lactic acid, and the flow rate is 0.4–1.0 cm per 100 grams of L-lactic acid material. 3 Polylactic acid can be obtained by heating and polymerizing air at 160-180℃.
[0005] In this invention, benzeneselenic acid, 4-methylbenzeneselenic acid, 4-chlorobenzeneselenic acid, 4-trifluoromethylbenzeneselenic acid, 4-fluorobenzeneselenic acid, 4-nitrobenzeneselenic acid, 2-fluorobenzeneselenic acid, 3-fluorobenzeneselenic acid, 1-naphthylselenic acid, 2-naphthylselenic acid, and 2-fluoro-1-naphthylselenic acid can all be used as catalyst precursors, but 2-fluoro-1-naphthylselenic acid is the most effective.
[0006] In this invention, the amount of catalyst precursor substituted for selenite is 0.02 to 0.08% of the mass of L-lactic acid, preferably 0.05%. The catalyst precursor itself is a strong acid; using too much is detrimental to polymerization, but using too little will prevent it from functioning properly.
[0007] In this invention, a flow rate of 0.4–1.0 cm⁻¹ is required. 3Air is blown in at a velocity of 0.7 cm / s. 3 The optimal air velocity is / s. Insufficient air leads to excessive reduction of substituted selenite to diselenide, deactivating the catalyst. Introducing an appropriate amount of air can suppress this reduction process. However, excessive air velocity will oxidize the substituted selenite active species back to substituted selenite, hindering the polymerization reaction.
[0008] In this invention, polymerization is carried out at 160–180°C, preferably 170°C. At low reaction temperatures, polymerization is difficult to occur, while at excessively high temperatures, the generated active selenium species are unstable, thus hindering the polymerization reaction.
[0009] Compared with existing technologies, the advantages of this invention are as follows: This synthesis method directly polymerizes L-lactic acid to PLA under metal-free conditions, and the synthesized polylactic acid does not require washing, i.e., it is metal-free. Furthermore, the direct synthesis of PLA from L-lactic acid bypasses the L-lactide synthesis step, making it more economical, and the synthesized polylactic acid reaches medical grade. Attached Figure Description
[0010] Figure 1 Schematic diagram of the mechanism of selenium-catalyzed L-lactic acid polymerization. Detailed Implementation
[0011] Example 1
[0012] A method for the selenium-catalyzed synthesis of polylactic acid, comprising the following steps:
[0013] (1) Preparation of selenium catalyst precursor: Various methods for preparing substituted diselenyl ethers are given in the literature (Appl. Organometal. Chem. 2014, 28, 652–656). Based on the literature, substituted selenite acid can be prepared by oxidizing diselenyl ether with hydrogen peroxide, which can be used as the catalyst precursor of this invention.
[0014] Taking the synthesis of 2-fluoro-1-naphthyl selenite as an example: This experiment was conducted in a fume hood. In a 250 mL three-necked round-bottom flask, one magnetic stir bar, 0.1 mol of magnesium powder, and one small grain of iodine (approximately 20 mg, serving as an initiator) were added, along with a condenser and an anhydrous calcium chloride drying tube. With magnetic stirring, 100 mL of anhydrous diethyl ether solution containing 0.1 mol of 2-fluoro-1-bromonaphthalene was slowly added dropwise to the magnesium powder through a dropping funnel. The reaction rate was controlled. Cooling in an ice-water bath could be used to prevent spillage. After the reaction was complete, a gray suspension was obtained. 0.1 mol of dry selenium powder was slowly added in portions to this liquid, stirring to ensure complete selenium insertion. After the reaction was complete, the reaction solution was poured into 200 mL of dilute hydrochloric acid (0.5 mol / L) cooled with ice. After stirring thoroughly, air was bubbled in (0.8 cm). 3The liquid was placed in a fume hood overnight. The next day, it was extracted with ether (100 mL ether each time, 3 times). The organic layers were combined and dried with anhydrous sodium sulfate. After filtration, the solvent was evaporated to obtain a yellow powder, which is 18.0 g of di(2-fluoro-1-naphthyl)diselenoether. 2.2 g of this powder was placed in a 10 mL beaker, and 2.5 mL of 30% hydrogen peroxide solution was added. After stirring, the yellow color disappeared. The mixture was placed in a vacuum desiccator and dried at 80 °C for 2 hours to obtain a white powder, which is 2-fluoro-1-naphthylselenoic acid.
[0015] (2) L-Lactic Acid Polymerization: In a 500 mL three-necked round-bottom flask, add one magnetic stir bar, 50 mg of 2-fluoro-1-naphthylselenoic acid, and 100 g of L-lactic acid. Attach a water separator, reflux condenser, and air inlet. Heat to 170 °C with magnetic stirring and introduce air (0.7 cm³). 3 The mixture was stirred at this temperature for 3 hours. Water produced during the reaction was collected using a water separator, while the bottom of the reaction flask gradually became viscous. After the reaction was complete, the mixture was cooled to room temperature, and 150 mL of dimethyl carbonate was added to a three-necked round-bottom flask. The mixture was heated to 60°C and stirred to dissolve. The solution was cooled to room temperature and poured into a large beaker containing 1 L of methanol, resulting in a large amount of white filamentous precipitate. The precipitate was separated by filtration. After drying in a vacuum desiccator at 60°C for 1 hour, 71 g of polymer was obtained, with a yield of 89%. Gel chromatography determined its number-average molecular weight to be 56450.
[0016] Example 2
[0017] Other conditions were the same as in Example 1, but different catalyst precursors were used to catalyze the reaction. The results are shown in Table 1.
[0018] Table 1 Results of catalytic reactions of precursors with different catalysts
[0019] serial number Catalyst precursor Yield (%) Number average molecular weight 1 2-Fluoro-1-naphthylselenoic acid (Example 1) 89 56450 2 bis(2-fluoro-1-naphthyl)diselenoether 12 3585 3 benzeneselenic acid 67 12975 4 4-Methylbenzene selenite 55 8905 5 4-Chlorobenzene selenite 71 22396 5 4-Trifluoromethylbenzene selenite 73 32099 6 4-Fluorobenzene selenite 72 31448 7 4-Nitrobenzene selenite 67 30085 8 2-Fluorobenzene selenite 74 36982 9 3-Fluorobenzene selenite 70 28812 10 1-Naphthoselenoic acid 76 48901 11 2-Naphthoselenoic acid 72 40023
[0020] As shown in the table above, benzeneselenic acid, 4-methylbenzeneselenic acid, 4-chlorobenzeneselenic acid, 4-trifluoromethylbenzeneselenic acid, 4-fluorobenzeneselenic acid, 4-nitrobenzeneselenic acid, 2-fluorobenzeneselenic acid, 3-fluorobenzeneselenic acid, 1-naphthylselenic acid, 2-naphthylselenic acid, and 2-fluoro-1-naphthylselenic acid can all be used as catalyst precursors, but 2-fluoro-1-naphthylselenic acid shows the best effect. The reaction mechanism is attached. Figure 1As shown, the catalyst precursor is reduced to substituted selenite (RSeOH) in L-lactic acid, and further condenses to substituted selenite anhydride (RSeOSeR). The nucleophilic attack of the carboxyl group of lactic acid on the substituted selenite anhydride is key to its catalytic polymerization. Therefore, the substituted selenite precursor has an electron-withdrawing group, which enhances the strength of its selenium positive charge center, making it easier for lactic acid to attack. Furthermore, excessive reduction of the substituted selenite to diselenide deactivates the catalyst, while the 1-naphthyl group, as a sterically hindered group, can suppress this side reaction.
[0021] Although diselenyl ether can theoretically be oxidized to the corresponding hyposelenic acid, using the corresponding diselenyl ether [di(2-fluoro-1-naphthyl)diselenyl ether] as a catalyst precursor results in very low yields and low molecular weights. This indicates that under these conditions, the oxidation of diselenyl ether to hyposelenic acid is difficult, thus exhibiting a decrease in yield and a reduction in product molecular weight. A comparison with the table above shows that the presence of electron-withdrawing groups and sterically hindered groups is beneficial to the reaction.
[0022] Example 3
[0023] Other conditions were the same as in Example 1, but different amounts of catalyst precursors were used for the reaction, and the results are shown in Table 2.
[0024] Table 2. Catalytic reaction results with different catalyst precursor dosages
[0025] serial number Catalyst precursor dosage (%) Yield (%) Number average molecular weight 1 0 0 - 2 0.01 15 18053 3 0.02 57 33219 4 0.03 74 43023 5 0.04 83 50274 5 0.05 (Example 1) 89 56450 6 0.06 89 51375 7 0.07 87 47021 8 0.08 85 40231 9 0.09 82 29629
[0026] As shown in the table above, this reaction requires a selenium catalyst to occur. Insufficient catalyst precursor will hinder the reaction, while excessive amounts, although having little impact on the yield, will significantly affect the degree of polymerization of the product. This is because selenite is a strong acid, and excessive amounts will make the reaction system too acidic, causing the polymer ester chains to hydrolyze and break, resulting in a decrease in the degree of polymerization.
[0027] Example 4
[0028] Under the same conditions as in Example 1, the effect was tested using air at different flow rates. The results are shown in Table 3, which corresponds to the air flow rate for 100 grams of L-lactic acid material.
[0029] Table 3 Effect of the inlet air flow rate on the reaction
[0030] serial number <![CDATA[Air flow velocity (cm 3 / s)]]> Yield (%) Number average molecular weight 1 0 22 4782 2 0.3 60 37621 3 0.4 73 44820 4 0.5 82 50218 5 0.6 87 55385 5 0.7 (Example 1) 89 56450 6 0.8 88 56012 7 0.9 86 53278 8 1.0 84 50321 9 1.1 80 45338
[0031] The results above show that without air introduction, the hyposelenic acid reactive compound is easily deactivated by reduction to diselenyl ether, leading to the cessation of the polymerization reaction, manifested as a significant decrease in product yield and a very low number-average molecular weight. Introducing an appropriate amount of air can inhibit this reduction process. However, when the airflow rate is too high, hyposelenic acid is oxidized to selenite, which is also detrimental to the reaction, resulting in a decrease in yield and number-average molecular weight. Therefore, the preferred airflow rate is 0.4-1.0 cm⁻¹. 3 / s; optimal value is 0.7cm 3 / s.
[0032] Example 5
[0033] Other conditions were the same as in Example 1, and the reaction was carried out at different temperatures. The experimental results are shown in Table 4.
[0034] Table 4 Effect of Temperature on Polymerization Reaction
[0035] serial number Reaction temperature (°C) Yield (%) Number average molecular weight 1 150 26 8742 2 160 67 41581 3 165 82 50273 4 170 (Example 1) 89 56450 5 175 83 54952 6 180 74 50214 7 190 61 41402
[0036] The results above show that polymerization is difficult to occur at low reaction temperatures; while at excessively high reaction temperatures, the generated selenoid is more easily oxidized, producing selenite and becoming deactivated, thus making polymerization even more difficult. The preferred polymerization temperature is 160-180℃, with 170℃ being the most preferred.
[0037] This invention is not limited to the above embodiments. Based on the technical solutions disclosed in this invention, those skilled in the art can make some substitutions and modifications to some of the technical features without creative effort, and all such substitutions and modifications are within the protection scope of this invention.
Claims
1. A method for the selenium-catalyzed synthesis of polylactic acid, characterized in that: Adding substituted selenite as a catalyst precursor to L - In lactic acid, the amount added is L - 0.02~0.08% of lactic acid by mass, per 100 grams L - Lactic acid feed inflow 0.4~1.0 cm 3 Polylactic acid can be obtained by heating and polymerizing air at 160~180℃, wherein the substituted selenite is 2-fluoro-1-naphthoselenic acid.
2. The method for selenium-catalyzed synthesis of polylactic acid according to claim 1, characterized in that: The amount of substituted selenite added is L -0.05% of the mass of lactic acid.
3. A method for the selenium-catalyzed synthesis of polylactic acid according to claim 1 or 2, characterized in that: The air flow rate introduced into the reaction is 0.7 cm. 3 / s.
4. A method for the selenium-catalyzed synthesis of polylactic acid according to claim 1 or 2, characterized in that: The polymerization reaction temperature is 170℃.