Method for synthesizing polylactic acid under catalysis of selenium

Abstract

The invention discloses a method for synthesizing polylactic acid under catalysis of selenium in the technical field of material chemistry. According to the method, substituted seleninic acid is used as a catalyst precursor and is added into L-lactic acid, the addition amount of the catalyst precursor is 0.02-0.08% of the mass of the L-lactic acid, 0.4-1.0 cm < 3 > / s of air is blown into every 100 g of L-lactic acid material, and polylactic acid can be obtained through heating polymerization at 160-180 DEG C. The method is simple to operate, and can avoid the use of a metal catalyst, so that metal residues in the product are avoided, and the medical-grade polylactic acid material can be directly prepared.

Description

Technical Field

[0001] The invention belongs to the field of material chemical preparation, and in particular relates to a method for preparing a medical-grade polylactic acid material. Background Art

[0002] In the medical field, L-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, the production of PLA that meets medical standards faces many major challenges, among which the control of metallic tin residues is particularly stringent. At present, PLA is mainly synthesized by the polymerization of L-lactide, and tin catalysts are used in the process, which easily leads to tin residues. Tin needs to be removed by washing, which increases costs. In addition, L-lactide is synthesized from L-lactic acid, a process that currently has a low yield, increases process costs, and is produced by solid waste. The development of a new method for synthesizing PLA by direct polymerization of L-lactic acid catalyzed by non-metallic catalysts can solve the above problems. Summary of the invention

[0003] The present invention develops a method for synthesizing polylactic acid by selenium catalysis, which uses selenium with higher biological tolerance as a catalyst to catalyze the direct polymerization of L-lactic acid to synthesize PLA under metal-free conditions. The polylactic acid synthesized by the method does not need to be washed, that is, it does not contain metal. In addition, PLA is directly synthesized from L-lactic acid, skipping the L-lactide synthesis step, which is more economical.

[0004] The object of the present invention is achieved by: a method for synthesizing polylactic acid catalyzed by selenium, wherein selenious acid is used as a catalyst precursor and added to L-lactic acid in an amount of 0.02 to 0.08% of the mass of the L-lactic acid, and a drum flow rate of 0.4 to 1.0 cm2 is applied to each 100 g of L-lactic acid material. 3 / s air, and heating polymerization at 160-180°C to obtain polylactic acid.

[0005] In the present invention, phenylselenous acid, 4-methylphenylselenous acid, 4-chlorophenylselenous acid, 4-trifluoromethylphenylselenous acid, 4-fluorophenylselenous acid, 4-nitrobenzeneselenous acid, 2-fluorophenylselenous acid, 3-fluorophenylselenous acid, 1-naphthaleneselenous acid, 2-naphthaleneselenous acid and 2-fluoro-1-naphthaleneselenous acid can all be used as catalyst precursors, but 2-fluoro-1-naphthaleneselenous acid has the best effect.

[0006] In the present invention, the amount of the catalyst precursor added to replace the selenious acid is 0.02-0.08% of the mass of L-lactic acid, preferably 0.05%. The catalyst precursor itself is a strong acid, and too much is not conducive to polymerization, but too little is not effective.

[0007] In the present invention, the flow rate is 0.4-1.0 cm 3 / s, the air is blown in, and the air flow rate is 0.7cm 3 / s is the best. When there is too little air, the substituted selenious acid is over-reduced to diselenide, which will deactivate the catalyst. The introduction of an appropriate amount of air can inhibit this reduction process. However, if the air flow rate is too fast, the active species of substituted selenous acid will be oxidized to substituted selenious acid, which is not conducive to the polymerization reaction.

[0008] In the present invention, the polymerization is carried out by heating at 160-180° C., preferably 170° C. If the reaction temperature is low, the polymerization reaction is difficult to occur, while if the reaction temperature is too high, the generated active selenium species are unstable, which is not conducive to the polymerization reaction.

[0009] Compared with the prior art, the invention has the following beneficial effects: the synthesis method can directly polymerize L-lactic acid to synthesize PLA under metal-free conditions, and the synthesized polylactic acid does not need to be washed, that is, it does not contain metal. Moreover, the direct synthesis of PLA from L-lactic acid skips the L-lactide synthesis step, which is more economical, and the synthesized polylactic acid can reach medical grade. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 The mechanism diagram of L-lactic acid polymerization catalyzed by selenium DETAILED DESCRIPTION

[0011] Example 1

[0012] A method for synthesizing polylactic acid using selenium catalysis, comprising the following steps:

[0013] (1) Preparation of selenium catalyst precursor: The literature (Appl. Organometal. Chem. 2014, 28, 652-656) provides methods for preparing various substituted diselenides. Based on the literature, it is only necessary to oxidize diselenides with hydrogen peroxide to prepare substituted selenious acid for use as the catalyst precursor of the present invention.

[0014] Take the synthesis of 2-fluoro-1-naphthyl selenous acid as an example: the experiment was carried out in a fume hood. Add 1 magnetic stirrer, 0.1 mol magnesium powder, 1 small iodine (about 20 mg, initiator) to a 250 ml three-necked round-bottom flask, and connect a condenser and anhydrous calcium chloride drying tube. Under magnetic stirring, slowly drip 100 ml of anhydrous ether solution containing 0.1 mol of 2-fluoro-1-bromonaphthalene onto the magnesium powder through a dropping funnel. Control the reaction rate. It can be cooled with an ice water bath to prevent the material from being washed away. After all the reactions are completed, a gray suspension is obtained. Slowly add 0.1 mol of dry selenium powder to the liquid in batches and stir to ensure that the selenium insertion reaction is sufficient. After the reaction is completed, pour the reaction solution into 200 mL of dilute hydrochloric acid (0.5 mol / L) cooled with ice cubes. After stirring evenly, blow in air (0.8 cm 3 / s) was placed in a fume hood overnight. The next day, the liquid was extracted with ether (100 ml of ether each time, extracted 3 times). The organic layers were combined and dried over anhydrous sodium sulfate. After filtering, the solvent was evaporated to obtain a yellow powder, which was di(2-fluoro-1-naphthyl) diselenide (18.0 g). 2.2 g of it was taken and placed in a 10 ml beaker, and 2.5 ml of 30% hydrogen peroxide solution was added thereto. After stirring, the yellow color faded. The mixture was placed in a vacuum dryer and dried at 80°C for 2 hours to obtain a white powder, i.e. 2-fluoro-1-naphthyl selenous acid.

[0015] (2) L-lactic acid polymerization: Place a magnetic stir bar, 50 mg of 2-fluoro-1-naphthyl selenous acid and 100 g of L-lactic acid in a 500 ml three-necked round-bottom flask. Install a water separator, reflux condenser and air duct. Heat to 170°C under magnetic stirring and introduce air (0.7 cm 3 / s). Stir at this temperature for 3 hours. The water produced by the reaction is collected by the water separator, and the bottom of the reaction bottle gradually becomes viscous. After the reaction is completed, cool to room temperature, add 150 ml of dimethyl carbonate to a three-necked round-bottom flask, heat to 60°C, and stir to dissolve. The solution is cooled to room temperature and poured into a large beaker containing 1 liter of methanol, and a large amount of white filamentous precipitates are produced. Filter and separate the precipitate. After drying at 60°C in a vacuum dryer for 1 hour, weigh and obtain 71 grams of polymer with a yield of 89%. The number average molecular weight is determined to be 56450 by gel chromatography.

[0016] Example 2

[0017] The other conditions were the same as in Example 1, and different catalyst precursors were used to catalyze the reaction. The results are shown in Table 1.

[0018] Table 1 Catalytic reaction results of different catalyst precursors

[0019] serial number Catalyst Precursor Yield (%) Number average molecular weight 1 2-Fluoro-1-naphthyl selenous acid (Example 1) 89 56450 2 Bis(2-fluoro-1-naphthyl) diselenide 12 3585 3 Phenylselenous acid 67 12975 4 4-Methylphenylselenous acid 55 8905 5 4-Chlorophenylselenous acid 71 22396 5 4-Trifluoromethylphenylselenous acid 73 32099 6 4-Fluorophenylselenous acid 72 31448 7 4-Nitrophenylselenous acid 67 30085 8 2-Fluorophenylselenous acid 74 36982 9 3-Fluorophenylselenous acid 70 28812 10 1-Naphthyl selenous acid 76 48901 11 2-Naphthylselenous acid 72 40023

[0020] As shown in the table above, phenylselenous acid, 4-methylphenylselenous acid, 4-chlorophenylselenous acid, 4-trifluoromethylphenylselenous acid, 4-fluorophenylselenous acid, 4-nitrobenzene selenous acid, 2-fluorophenylselenous acid, 3-fluorophenylselenous acid, 1-naphthaleneselenous acid, 2-naphthaleneselenous acid and 2-fluoro-1-naphthaleneselenous acid can all be used as catalyst precursors, but 2-fluoro-1-naphthaleneselenous acid has the best effect. The reaction mechanism is shown in the attached figure. Figure 1As shown. The catalyst precursor will be reduced to substituted selenous acid (RSeOH) in L-lactic acid, and further condensed into substituted selenoic anhydride (RSeOSeR). The nucleophilic attack of the carboxyl group of lactic acid on substituted selenoic anhydride is the key to its catalytic polymerization. Therefore, the substituted selenous acid precursor is connected with an electron-withdrawing group, which is conducive to enhancing the strength of its selenium positive center, making it easy to be attacked by lactic acid. In addition, the excessive reduction of substituted selenous acid to diselenide will inactivate the catalyst, and 1-naphthyl, as a large steric hindrance group, can inhibit this side reaction.

[0021] Although diselenide can be oxidized and converted into the corresponding selenous acid in theory, the yield and molecular weight of the corresponding diselenide [bis(2-fluoro-1-naphthyl) diselenide] as a catalyst precursor are very low. This shows that under this condition, it is difficult to oxidize diselenide to selenous acid, resulting in a decrease in yield and a decrease in product molecular weight. By comparing the above table, it can be seen that the presence of electron-withdrawing groups and large steric hindrance groups is conducive to the reaction.

[0022] Example 3

[0023] The other conditions were the same as in Example 1, and different amounts of catalyst precursor were used for the reaction. The results are shown in Table 2.

[0024] Table 2 Catalytic reaction results of 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 results in the table above, the reaction requires a selenium catalyst to occur. If the amount of catalyst precursor is insufficient, it will be unfavorable for the reaction, but if it is excessive, although it has little effect on the yield, it will have a significant effect on the degree of polymerization of the product. This is because selenious acid itself is a strong acid, and excessive use will make the reaction system too acidic, thereby causing the polymer ester chain to hydrolyze and break, resulting in a decrease in the degree of polymerization.

[0027] Example 4

[0028] The other conditions were the same as those in Example 1, and the air flow rates were different to test the effect. The results are shown in Table 3, which corresponds to the air flow rate for 100 g of L-lactic acid material.

[0029] Table 3 Effect of air flow rate on 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] As can be seen from the above results, when air is not introduced, the selenogenic acid active substance is easily inactivated by reduction to diselenide, which causes the polymerization reaction to stop, which is manifested as a significant decrease in product yield and a very low number average molecular weight. Blowing in an appropriate amount of air can inhibit this reduction process. However, when the air flow rate is too fast, selenogenic acid is oxidized to selenous acid, which is also not conducive to the reaction, thereby manifesting as a decrease in yield and number average molecular weight. Therefore, the air flow rate is preferably 0.4-1.0cm 3 / s; the most preferred is 0.7cm 3 / s.

[0032] Example 5

[0033] Other conditions were the same as in Example 1, and the reactions were 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 (℃) 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] From the above results, it can be seen that when the reaction temperature is low, the polymerization reaction is difficult to occur; when the reaction temperature is too high, the generated selenous acid is more easily oxidized to produce selenious acid and deactivate, which makes the polymerization reaction difficult to occur. The polymerization temperature is preferably 160-180°C, and most preferably 170°C.

[0037] The present invention is not limited to the above-mentioned embodiments. On the basis of the technical solution disclosed in the present invention, technicians in this field can make some substitutions and deformations to some technical features therein according to the disclosed technical content without creative labor, and these substitutions and deformations are all within the protection scope of the present invention.

Claims

1. A method for synthesizing polylactic acid using selenium catalysis, characterized in that: Substituted selenous acid as a catalyst precursor is added to L -Lactic acid, added in an amount of L - 0.02~0.08% of lactic acid mass per 100g L - Lactic acid material drum flow 0.4~1.0 cm 3 / s air, and heating polymerization at 160~180℃ to obtain polylactic acid.

2. The method for synthesizing polylactic acid using selenium catalysis according to claim 1, characterized in that: The added substituted selenious acid is one of phenylselenous acid, 4-methylphenylselenous acid, 4-chlorophenylselenous acid, 4-trifluoromethylphenylselenous acid, 4-fluorophenylselenous acid, 4-nitrobenzene selenous acid, 2-fluorophenylselenous acid, 3-fluorophenylselenous acid, 1-naphthaleneselenous acid, 2-naphthaleneselenous acid and 2-fluoro-1-naphthaleneselenous acid.

3. The method for synthesizing polylactic acid using selenium catalysis according to claim 2, characterized in that: The substituted selenous acid added was 2-fluoro-1-naphthylselenous acid.

4. A method for synthesizing polylactic acid catalyzed by selenium according to any one of claims 1 to 3, characterized in that: The amount of substituted selenious acid added is L -0.05% by mass of lactic acid.

5. A method for synthesizing polylactic acid catalyzed by selenium according to any one of claims 1 to 3, characterized in that: The air flow rate into the reaction was 0.7 cm 3 / s.

6. A method for synthesizing polylactic acid catalyzed by selenium according to any one of claims 1 to 3, characterized in that: The polymerization temperature was 170°C.

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