A method for rapidly synthesizing l-lactide

Abstract

This invention relates to a rapid synthesis method in the field of chemical production technology. L - The method of lactide, which first involves... L Lactic acid undergoes rapid prepolymerization catalyzed by trifluoromethanesulfonate, followed by the addition of a zinc-doped polypyrrole catalyst and a diamine ligand, and then pyrolysis is performed under reduced pressure to obtain the target product. L The method involves adding lactide; the molar amount of trifluoromethanesulfonate is 0.1-0.7% of the molar amount of lactic acid; the mass of zinc-doped polypyrrole catalyst added is 0.05-0.4% of the mass of lactic acid; and the molar amount of diamine ligand added is 0.3-2.1% of the molar amount of lactic acid. This method can overcome the racemic reaction in the production process to obtain high-purity lactide. L -Lactose-lactide.

Description

Technical Field

[0001] This invention belongs to the field of chemical production technology, specifically relating to the field of catalytic generation technology of L-lactide. Background Technology

[0002] Polylactic acid (PLA), also known as polylactide, is a biodegradable material. On one hand, its biodegradability allows for the production of environmentally friendly materials, overcoming the white pollution caused by the non-degradability of traditional plastics. On the other hand, and more importantly, its biodegradability enables its application in the medical field, for example, in the manufacture of surgical sutures. High-end applications of PLA lie in the manufacture of medical materials, products with substantial profit margins but requiring high mechanical properties. The mechanical properties of PLA are determined by its synthesis process. Currently, PLA prepared by direct polymerization of L-lactic acid has a small molecular weight, resulting in poor mechanical properties that fail to meet the quality requirements for medical consumables. In contrast, PLA prepared by polymerization using L-lactide has a larger molecular weight and stronger mechanical properties, making it suitable for high-end medical consumables. Therefore, it can be said that the technology for producing L-lactide is one of the bottlenecks restricting the production of biodegradable medical consumables. L-lactide is an important raw material. There are two quality indicators for L-lactide: chemical purity and optical purity. Optical purity directly relates to its biodegradability and is crucial for its medical applicability. In fact, the raw material lactic acid used to prepare L-lactide is itself high-purity L-lactic acid. However, due to process limitations, partial racemization occurs during the lactic acid prepolymerization stage, affecting the optical purity of the subsequently produced L-lactide. Overcoming racemization is a key technical challenge in this field. Summary of the Invention

[0003] The purpose of this invention is to provide a rapid method for synthesizing L-lactide, which can overcome the racemic reaction in the production process to obtain high-purity L-lactide.

[0004] Therefore, this invention provides a method for the rapid synthesis of L-lactide, which involves first rapidly prepolymerizing L-lactic acid under the catalysis of trifluoromethanesulfonate, then adding a zinc-doped polypyrrole catalyst and a diamine ligand, followed by pyrolysis under reduced pressure to obtain the target product, lactide. The molar amount of trifluoromethanesulfonate added is 0.1–0.7% of the molar amount of L-lactic acid; the mass of the zinc-doped polypyrrole catalyst added is 0.05–0.4% of the mass of L-lactic acid; and the molar amount of the diamine ligand added is 0.3–2.1% of the molar amount of L-lactic acid.

[0005] Adding an acidic catalyst during the prepolymerization step of L-lactic acid can accelerate the reaction, but the acid may also promote racemization; simultaneously, the acidic catalyst may interfere with subsequent pyrolysis reactions. This invention uses trifluoromethanesulfonate, a Lewis acid rather than a protic acid, to catalyze the prepolymerization reaction. The advantages are twofold: firstly, the metal in the Lewis acid can coordinate with lactic acid, thus providing a stabilizing effect and preventing racemization; secondly, in the subsequent pyrolysis stage, ligands can be added to weaken the acidity of the Lewis acid, preventing it from disrupting the pyrolysis reaction. The ligands act as a "negative catalyst." The pyrolysis reaction is actually achieved by the nucleophilic groups in the pyrolysis catalyst attacking the lactic acid oligomers. Since the metal in the Lewis acid can coordinate with the nucleophilic groups, introducing additional ligands to occupy the metal vacancies in the Lewis acid can prevent them from disrupting the pyrolysis reaction. This invention is used to prepare high-purity L-lactide.

[0006] Furthermore, the trifluoromethanesulfonate is one of iron trifluoromethanesulfonate, zinc trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, cerium trifluoromethanesulfonate, scandium trifluoromethanesulfonate, and copper trifluoromethanesulfonate. Ytterbium trifluoromethanesulfonate is preferred. The aforementioned Lewis acids have strong acidity and high catalytic efficiency, resulting in a high product purity.

[0007] A further improvement of this invention is that the molar amount of trifluoromethanesulfonate added is 0.4% of the molar amount of L-lactic acid. This amount ensures the prepolymerization reaction rate and avoids interference with the subsequent cracking reaction due to excessive Lewis acid catalyst, which would lead to a decrease in yield.

[0008] A further improvement of the present invention is that the amount of zinc-doped polypyrrole catalyst added is 0.2% of the mass of L-lactic acid. This amount ensures that the pyrolysis reaction is complete.

[0009] A further improvement of this invention is that the amount of diamine ligand added is 1.2% of the molar amount of L-lactic acid. In fact, this amount is exactly three times the molar amount of the Lewis metal. Theoretically, the ligand only needs to be used in equal amounts to the Lewis acid metal. However, in practice, on the one hand, because the ligand is a relatively small molecular weight organic compound, it has a certain degree of volatility and will be partially lost due to volatilization; on the other hand, an excess of ligand is beneficial for full coordination, and its amount needs to be three times the amount of the metal to sufficiently eliminate the adverse effects of the Lewis acid metal on the cracking reaction.

[0010] Furthermore, the added diamine ligand is one of ethylenediamine, 1,3-propanediamine, 1,4-butanediamine, 1,5-pentanediamine, 1,3-diaminopentane, 2,4-diaminopentane, 1,4-diaminopentane, o-phenylenediamine, and m-phenylenediamine. Preferably, it is 1,3-diaminopentane. The distance between the two amino groups in this ligand is precisely suited to the Lewis acid metal radius, allowing for a more robust complex formation and eliminating the influence of the Lewis acid catalyst added during the prepolymerization stage. In addition, this substance has a high boiling point, making it less prone to loss due to volatilization. The substance also exhibits low steric hindrance (due to the presence of one amine at the end), resulting in minimal steric hindrance impact during metal complexation. Detailed Implementation

[0011] Example 1

[0012] I. Preparation of Pyrolysis Catalysts

[0013] Preparation of polypyrrole: Using 75 mL of deionized water and 75 mL of ethanol as solvents, a magnetic stir bar was placed in the solution, and 2.5 mL of pyrrole monomer was added dropwise. 6 g of ammonium persulfate was dissolved in 15 mL of water as an initiator, and this solution was added dropwise to the pyrrole solution over approximately 30 minutes. During the dropwise reaction, the pyrrole solution was observed to gradually turn green and then black. After the addition was complete, the reaction was allowed to proceed for 24 hours. The mixture was then filtered using a vacuum filtration flask, washed with deionized water, and powdered polypyrrole (PPy) was obtained. This powder was dried in an oven, and the yield (polypyrrole weight / pyrrole weight) reached 83%.

[0014] Preparation of zinc-doped polypyrrole (Zn@PPy): 2.5 g of zinc oxide and 61.5 mL of 1 mol / L dilute hydrochloric acid were added to a beaker to prepare a zinc chloride solution. The pH was adjusted to 2.5 by adding more hydrochloric acid. Then, 2 g of dried polypyrrole was added to the prepared zinc chloride solution, followed by 10 mL of deionized water. A magnetic stir bar was added, and the mixture was stirred at a constant temperature of 80 °C for 2 h. After the reaction, the mixture was filtered, and the filter cake was washed with deionized water (10 mL × 3), and dried at 50 °C for 24 h to obtain 1.9 g of Zn@PPy catalyst. Inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that the zinc content was 1.04%.

[0015] II. Preparation of L-lactide:

[0016] A magnetic stir bar, 50 g of L-lactic acid (molecular weight 90.8 g / mol, optical purity 99.9%), and 2.2 mmol of ytterbium trifluoromethanesulfonate (CAS No. 54761-04-5, 0.4% of the molar amount of L-lactic acid) were added to a 250 mL four-necked flask equipped with a condenser, thermometer, and vacuum pump. The reaction system was heated to 150 °C and stirred at atmospheric pressure for 1 h, followed by stirring at 48.0 kPa for 0.5 h, and then stirring at 1.3 kPa for another 0.5 h to produce PLA oligomers and remove the byproduct water. After the prepolymerization reaction was completed, 100 mg of Zn@PPy catalyst (0.2% of the mass of L-lactic acid) and 6.7 mmol of 1,3-diaminopentane (CAS No. 589-37-7, 1.2% of the molar amount of L-lactic acid) were added. The mixture was subjected to a pyrolysis reaction under stirring at 220°C and 1.3 kPa, and the crude lactide produced was collected within 3 hours. The crude lactide was purified by recrystallization from ethyl acetate, with a yield of 76%. The optical rotation of the product was measured using a polarimeter, and compared with data from a standard sample under the same conditions, revealing an optical purity of 99.4%.

[0017] Example 2

[0018] Other conditions were the same as in Example 1, but different prepolymer catalysts were used to catalyze the reaction. The experimental results are shown in Table 1.

[0019] Table 1 shows the effects of using different prepolymer catalysts.

[0020]

[0021] As shown above, ytterbium trifluoromethanesulfonate was the most effective prepolymerization catalyst (Example 1). Compared to our previous work (Chin. J. Org. Chem. 2022, 42, 2954-2960), we shortened the prepolymerization time at 150°C from 3 hours to 1 hour. During this time, ytterbium trifluoromethanesulfonate could fully catalyze the prepolymerization reaction, resulting in two advantages: firstly, sufficient prepolymerization leads to a higher yield of lactide; secondly, after sufficient prepolymerization, L-lactic acid is no longer present in the system, thus preventing the promotion of racemic reactions in the subsequent pyrolysis stage, resulting in higher optical purity of the L-lactide product. Other prepolymerization catalysts are difficult to achieve these effects.

[0022] Example 3

[0023] Other conditions were the same as in Example 1, but different amounts of prepolymer catalyst (ytterbium trifluoromethanesulfonate) were used to catalyze the reaction. The experimental results are shown in Table 2.

[0024] Table 2 shows the effects of using different amounts of prepolymer catalyst.

[0025]

[0026]

[0027] As shown above, using 0.4 mol% prepolymer catalyst yields the best results. Insufficient prepolymer catalyst will compromise both lactide yield and optical purity. Excessive prepolymer catalyst will cause a rapid decrease in yield, demonstrating its significant destructive effect on the cracking process.

[0028] Example 4

[0029] Other conditions were the same as in Example 1, but different amounts of zinc-doped polypyrrole catalyst were used to catalyze the cracking reaction, and the results are shown in Table 3.

[0030] Table 3 shows the catalytic cracking effect of different amounts of zinc-doped polypyrrole catalyst.

[0031]

[0032]

[0033] As mentioned above, the optimal dosage of zinc-doped polypyrrole catalyst is 0.2% of the lactic acid mass. This catalyst primarily catalyzes the cracking reaction, its principle being that pyrrole nitrogen attacks the lactic acid polymer, opening the polymer chain and forming an L-lactide ring. Insufficient dosage leads to incomplete cracking, resulting in a reduced L-lactide yield. Excessive dosage, however, does not increase the L-lactide yield but instead raises the catalyst cost.

[0034] Example 5

[0035] Other conditions were the same as in Example 1, but different ligands were used in the pyrolysis stage to eliminate the influence of the prepolymer Lewis acid catalyst, and the results are shown in Table 4.

[0036] Table 4 shows the effect of using different ligands to eliminate the influence of prepolymer Lewis acid catalyst during the cracking stage.

[0037]

[0038]

[0039] As shown above, the ligand structure has a significant impact on its effectiveness. Because the bidentate spacing is suitable for the atomic radius of the metal, diamine ligands at the 1,3- and 2,4-positions are preferable, but the specific effect also depends on their volatility and steric hindrance. The ligand 1,3-diaminopentane, with its low volatility, minimal loss, and low steric hindrance, shows the best effect (Example 1). Aromatic ligands are ineffective due to the rigidity of the aromatic ring.

[0040] Example 6

[0041] Other conditions were the same as in Example 1, but different amounts of ligands were used in the pyrolysis stage to eliminate the influence of Lewis acid catalysts in the prepolymerization process. The results are shown in Table 5.

[0042] Table 5 shows the effectiveness of using different amounts of ligands in the cracking stage to eliminate the influence of Lewis acid catalysts during prepolymerization.

[0043]

[0044] As described above, ligands can eliminate the influence of Lewis acid catalysts during prepolymerization. Insufficient ligands can disrupt the cracking process and reduce yield, but have little impact on optical activity. Excessive ligand use does not improve yield but results in waste.

[0045] 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 rapid synthesis L The method for producing lactide, characterized in that First L Lactic acid undergoes rapid prepolymerization catalyzed by trifluoromethanesulfonate, followed by the addition of a zinc-doped polypyrrole catalyst and a diamine ligand, and then cleavage under reduced pressure to obtain the target product, lactide. The molar amount of trifluoromethanesulfonate added is 0.3-0.6% of the molar amount of lactic acid; the mass of the zinc-doped polypyrrole catalyst added is... L - 0.15-0.4% of the mass of lactic acid; the molar amount of the added diamine ligand is... L - Lactic acid molar amount 0.9-2.1%; the diamine ligand is 1,3-diaminopentane; the trifluoromethanesulfonate is ytterbium trifluoromethanesulfonate.

2. A rapid synthesis according to claim 1 L - A method for producing lactide, characterized in that: The molar amount of trifluoromethanesulfonate added is L -0.4% of the molar amount of lactic acid.

3. A rapid synthesis according to claim 1 L - A method for producing lactide, characterized in that: The amount of zinc-doped polypyrrole catalyst added was L -0.2% of the mass of lactic acid.

4. A rapid synthesis according to claim 1 L - A method for producing lactide, characterized in that: The amount of diamine ligand added is L -1.2% of the molar amount of lactic acid.

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