A zinc complex of a tetranuclear cubane configuration and a preparation method and application thereof

Abstract

This invention belongs to the field of metal complex preparation and application, and discloses a tetranuclear cuboane-configured zinc complex, its preparation method, and its application. The tetranuclear cuboane-configured zinc complex is used to catalyze the ring-opening polymerization of lactide. Using the tetranuclear cuboane-configured zinc complex as a catalyst and racemic lactide as a raw material, under anhydrous, oxygen-free, and inert gas protection conditions, in bulk conditions, the ring-opening polymerization of lactide can be catalyzed to prepare polylactide without the participation of a co-catalyst. The catalyst preparation method is simple, the catalyst is non-toxic, has a novel structure, high catalytic activity, and requires a low catalyst dosage during the catalytic process.

Description

Technical Field

[0001] This invention belongs to the field of metal complex catalyst preparation and application, specifically relating to the application of a tetranuclear cubane-configured β-ketoimine zinc complex in the catalytic ring-opening polymerization of lactide and its preparation method. Background Technology

[0002] Polylactide (PLA) is a polymer material with good biocompatibility and biodegradability. It possesses high tensile strength and excellent ductility, and can ultimately decompose into carbon dioxide and water within the human body. Therefore, it is widely considered an ideal biomedical material with significant research value, applicable to drug delivery systems, surgical sutures, and artificial tissue engineering. Currently, there are three main methods for synthesizing PLA. The first is direct polymerization, which involves the direct dehydration condensation of lactic acid under a catalyst to prepare PLA. This method is simple but can only be used to synthesize low molecular weight PLA because the condensation of lactic acid is a reversible reaction, and the generated water hinders the forward reaction. As the reaction proceeds, the PLA molecules grow, and the viscosity of the reaction system gradually increases, encapsulating the water and making it difficult to remove, thus hindering the synthesis of high molecular weight PLA. The second method is dehydration azeotropic polymerization. This method adds a solvent to the original reaction system, allowing most of the water to be removed under mild conditions, while the small amount of water remaining in the reaction mixture can be removed along with the solvent under high vacuum. After drying, the solvent is returned to the reaction system. The main drawback of this method is that the solvent is difficult to completely remove from the product. PLA products containing residual solvent are unsuitable for the biomedical field, and completely removing the organic solvent requires extremely advanced separation and purification techniques and incurs higher costs. Furthermore, this method also suffers from long reaction times and the inability to synthesize higher molecular weight PLA. The third method is ring-opening polymerization, which first polymerizes lactic acid to produce a dimer, lactide, and then the lactide undergoes ring-opening polymerization to produce polylactic acid. This method has mild reaction conditions, few side reactions, and no small molecule byproducts, making it easy to obtain high molecular weight polymers. It also features fast polymerization rates, high monomer conversion rates, and strong controllability of molecular weight and molecular weight distribution, giving it significant advantages in the synthesis of biomedical and biodegradable materials.

[0003] Currently, the synthesis of industrial-grade polylactide (PLD) mainly relies on the ring-opening polymerization of LPD catalyzed by stannous octoate. However, tin itself is toxic, and trace amounts of the metal inevitably remain in the polymer, which is harmful to human health. This limits the application of PLD in food packaging and biopharmaceutical fields. Therefore, developing environmentally compatible, non-toxic, or low-toxicity metal catalysts to promote green production processes for PLD has become an urgent and important task. Summary of the Invention

[0004] To overcome the shortcomings of the prior art, this invention provides a tetranuclear cuboethane-based zinc complex, its preparation method, and its application. Using a tetranuclear N-alkoxy-β-ketoimine zinc complex as a catalyst and racemic lactide as a raw material, under anhydrous, oxygen-free, and inert gas protection conditions, and under bulk conditions, polylactide can be prepared by catalyzing the ring-opening polymerization of lactide with low catalyst dosage without the need for a co-catalyst.

[0005] The above-mentioned objective of this invention is achieved through the following technical solution: A tetranuclear cuboethane-configured zinc complex having a structure as shown in general formula I: Ⅰ Where R is -(CH2)4-, -CH(CH3)(CH2)2-, -( R )-CH(CH3)CH2-、-( S )-CH(CH3)CH2CH2-, -CH2CH(CH3)-, -( S Any one of )-CH2CH(CH3)-.

[0006] Another object of the present invention is to protect the method for preparing the above-mentioned tetranuclear cubane zinc complex, specifically including the following steps: Under inert gas protection, ZnEt2 was added dropwise to a solution of a β-ketoimine ligand with the structure of general formula II and reacted for 3–7 h within a temperature range of 40 °C to 90 °C to obtain a zinc complex with a tetranuclear cubane configuration; the structure of general formula II is as follows: II Where R is -(CH2)4-, -CH(CH3)(CH2)2-, -( R )-CH(CH3)CH2-、-( S )-CH(CH3)CH2CH2-, -CH2CH(CH3)-, -( S Any one of )-CH2CH(CH3)-.

[0007] Furthermore, in the preparation method of the tetranuclear cubane-type zinc complex, the molar ratio of β-ketoimine ligand with structure such as general formula II to ZnEt2 is 1:0.8 to 1:1.3.

[0008] Furthermore, in the method for preparing the zinc complex with the tetranuclear cubane configuration, the solvent in the β-ketoimine ligand solution with the structure of general formula II is one of toluene and tetrahydrofuran.

[0009] Furthermore, in the method for preparing the tetranuclear cubane-configured zinc complex, the solvent in the ZnEt2 solution is either toluene or n-hexane.

[0010] Furthermore, in the preparation method of the zinc complex with the tetranuclear cuboethane configuration, the inert gas is argon or nitrogen.

[0011] Another object of the present invention is to protect the application of zinc complexes with a tetranuclear cuboethane configuration.

[0012] Furthermore, the application of the tetranuclear cuboethane-configured zinc complex specifically refers to its application in the catalytic ring-opening polymerization of racemic lactide.

[0013] The advantages of this invention compared to existing technologies are as follows: This invention develops a novel tetranuclear cubane-based zinc complex, its preparation method, and its applications. Using a tetranuclear N-alkoxy-β-ketoimine zinc complex as a catalyst and racemic lactide as a raw material, polylactide can be prepared by ring-opening polymerization of lactide under anhydrous, oxygen-free, and inert gas protection conditions without the need for a co-catalyst. The catalyst is non-toxic and requires a low dosage; the preparation method is simple, the structure is novel, and the catalytic activity is high. The resulting polymer has a good molecular weight distribution (1.07~2.50) and a controllable molecular weight (26.7 kg / mol~71.9 kg / mol). Attached Figure Description

[0014] Figure 1 A schematic diagram of the crystal structure of the zinc complex 2e with a tetranuclear cuboethane configuration. Detailed Implementation

[0015] The present invention will be described in detail below with reference to the embodiments. However, the following embodiments are only preferred embodiments of the present invention. The scope of protection of the present invention is not limited thereto. Any equivalent substitutions or changes made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention. The experimental methods used in the present invention are all conventional methods. The ligands 1a-1f are prepared according to the reference (Macromolecular Rapid Communications, 2023, 44(3): 2200663.). The experimental equipment, materials, reagents, etc. used can all be obtained from commercial sources.

[0016] The reaction formulas for the following embodiments are: Example 1 Synthesis of [CH3C(O)C(CH3)CN(CH2CH2CH2CH2O)CH3]4Zn4 (2a): Under argon atmosphere, 1a (0.25 g, 1.3 mmol) was completely dissolved in tetrahydrofuran. Diethylzinc (0.65 mL, 2 min n-Hexane, 1.3 mmol) was added dropwise to the system at 50 °C. After 4 h of reaction, when no more bubbles appeared, the reaction was terminated, yielding a yellow transparent solution. The solvent was removed by cold trap after cooling to room temperature to obtain a yellow crude complex powder. After removing the solvent, the vacuum ester and a slight excess of diethylzinc were washed away with n-hexane to obtain a yellow powder. The product was characterized by NMR. Yield: 0.30 g (94%). 1 H NMR (500 MHz, CDCl3): δ = 4.06-3.22 (m, 16H), 2.34-0.75 (m, 52H). 13 C NMR (101 MHz, CDCl3): δ = 179.6, 172.8, 97.7, 61.3, 43.1, 29.7, 27.9, 26.4, 15.1, 14.5. Example 2 Synthesis of [CH3C(O)C(CH3)CN(CH(CH3)CH2CH2O)CH3]4Zn4 (2b): Under argon atmosphere, 1b (0.25 g, 1.3 mmol) was completely dissolved in tetrahydrofuran. Diethylzinc (0.65 mL, 2 min n-Hexane, 1.3 mmol) was added dropwise to the system at 50 °C. After 5 h, no bubbles were observed, indicating the reaction was complete and a yellow transparent solution was obtained. The solvent was removed by cold trap after cooling to room temperature to obtain a yellow crude complex powder. After removing the solvent, the vacuum ester and a slight excess of diethylzinc were washed away with n-hexane to obtain a yellow powder. The product was characterized by NMR. Yield: 0.29 g (90%). 1 H NMR (500 MHz, CDCl3): δ = 4.44-3.47 (m, 12H), 2.38-0.76 (m, 56H). 13 C NMR (126 MHz, CDCl3): δ = 178.2, 172.3, 97.8, 69.4, 58.5, 40.1,30.3, 28.2, 14.9, 14.7. Example 3 [( RSynthesis of 1c-CH3C(O)C(CH3)CN(CH(CH3)CH2O)CH3]4Zn4 (2c): Under argon atmosphere, 1c (0.25 g, 1.5 mmol) was completely dissolved in tetrahydrofuran. Diethylzinc (0.75 mL, 2 M in Toluene, 1.5 mmol) was added dropwise to the system at 60 °C. After 5 h, no bubbles were observed, indicating the reaction was complete and a yellow transparent solution was obtained. The solvent was removed by cold trap after cooling to room temperature to obtain a yellow crude complex powder. After removing the solvent, the vacuum ester and a slight excess of diethylzinc were washed away with n-hexane to obtain a yellow powder. The product was characterized by NMR. Yield: 0.31 g (89%). 1 H NMR (400 MHz, CDCl3): δ = 4.55-3.00 (m, 12H), 2.22-0.79 (m, 48H). 13 C NMR (126 MHz, CDCl3): δ = 179.9, 173.0, 98.0, 66.4, 50.8, 28.1,20.8, 15.4, 14.8. Example 4 [( S Synthesis of 1-CH3C(O)C(CH3)CN(CH(CH3)CH2CH2O)CH3]4Zn4 (2d): Under argon atmosphere, 1d (0.25 g, 1.3 mmol) was completely dissolved in toluene. Diethylzinc (0.65 mL, 2 min n-Hexane, 1.3 mmol) was added dropwise to the system at 60 °C. After 5 h, no bubbles were observed, indicating the reaction was complete and a yellow transparent solution was obtained. After cooling to room temperature, the solvent was removed using a cold trap to obtain a yellow crude complex powder. After removing the solvent, the vacuum ester and a slight excess of diethylzinc were washed away with n-hexane to obtain a yellow powder. The product was characterized by NMR and elemental analysis. Yield: 0.30 g (93%). 1 H NMR (400 MHz, CDCl3): δ = 4.30-3.21 (m, 12H), 2.14-0.74 (m, 56H). 13 C NMR (126 MHz, CDCl3): δ = 178.2, 172.3, 97.8, 69.4,58.5, 40.1, 30.3, 28.2, 14.9, 14.7. Calcd for C 40 H 68Zn4N4O8: C, 57.87; H, 8.26; N, 6.75. Found: C, 58.04; H, 8.55; N, 6.43. Example 5 Synthesis of [CH3C(O)C(CH3)CN(CH(CH3)CH2O)CH3]4Zn4 (2e): Under argon atmosphere, 1e (0.25 g, 1.5 mmol) was completely dissolved in tetrahydrofuran. Diethylzinc (0.75 mL, 2 M in Toluene, 1.5 mmol) was added dropwise to the system at 50 °C. After 4 h, no bubbles were observed, indicating the reaction was complete and a yellow transparent solution was obtained. The solvent was removed by cold trap after cooling to room temperature to obtain a yellow crude complex powder. After removing the solvent, the vacuum ester and a slight excess of diethylzinc were washed away with n-hexane to obtain a yellow powder. The product was characterized by NMR. Yield: 0.31 g (88%). 1 H NMR (400 MHz, CDCl3): δ = 4.55-3.00 (m, 12H), 2.22-0.79 (m, 48H). 13 C NMR (101 MHz, CDCl3): δ = 178.7, 172.6, 96.6, 69.4, 56.9, 27.0,20.9, 18.4, 16.6. Example 6 [( S Synthesis of 1-CH3C(O)C(CH3)CN(CH(CH3)CH2O)CH3]4Zn4 (2f): Under argon atmosphere, 1f (0.25 g, 1.5 mmol) was completely dissolved in toluene. Diethylzinc (0.75 mL, 2 M in Toluene, 1.5 mmol) was added dropwise to the system at 80 °C. After 3 h, no bubbles were observed, indicating the reaction was complete and a yellow transparent solution was obtained. After cooling to room temperature, the solvent was removed using a cold trap to obtain a yellow crude complex powder. After removing the solvent, the vacuum ester and a slight excess of diethylzinc were washed away with n-hexane to obtain a yellow powder. The product was characterized by NMR and elemental analysis. Yield: 0.27 g (78%). 1 H NMR (400 MHz, CDCl3): δ = 4.55-3.00 (m, 12H), 2.22-0.79 (m, 48H). 13C NMR (101 MHz, CDCl3): δ = 178.7, 172.6, 96.6, 69.4,57.0, 26.5, 20.9, 18.4, 16.5. Calcd for C 36 H 60 Zn4N4O8: C, 55.86, H, 7.81, N,7.24. Found: C, 56.22; H, 7.99; N, 6.87. Example 7 A method for catalytic ring-opening polymerization of lactide using a tetranuclear cubane zinc complex 2a at a catalyst-to-monomer molar ratio of 3000:1, the method comprising the following steps: Under argon protection, accurately weigh the monomer (1.96 mmol) and zinc complex (0.00065 mmol) solids and stir thoroughly. Heat to 130 °C and observe the reaction system until the magnetic stirrer stops or the powder completely transforms into a gel solid. Record the reaction time (t = 30 s). Open the bottle cap, cool in an ice-water bath, add a small amount (1 mL) of CH2Cl2 to dissolve, and take a small sample from the reaction mixture to remove volatiles under vacuum. 1 The monomer conversion rate was calculated by H NMR (conv. = 86%).

[0017] The reaction mixture was subjected to vigorous stirring followed by the addition of a large amount (10 mL) of cold methanol solution for precipitation to obtain crude polymer. The polymer was then separated and washed with a small amount of cold methanol to remove residual catalyst and oligomers. This washing operation was repeated three times. The remaining solvent was then dried under vacuum at high temperature to obtain pure polymer. Gel permeation chromatography (GPC) analysis revealed the polymer's molecular weight (Mn) to be 71.9 kg / mol and its molecular weight distribution to be... Ð = 1.77.

[0018] Example 8 The method for catalytic ring-opening polymerization of lactide using a tetranuclear cubane-configured zinc complex 2b at a catalyst-to-monomer molar ratio of 3000:1 is the same as in Example 7. The differences from Example 7 are: weighing of monomer (1.88 mmol) and zinc complex (0.00063 mmol), catalytic reaction time t = 13 s, monomer conversion conv. = 77%, polymer molecular weight Mn = 46.2 kg / mol, and polymer molecular weight distribution. Ð = 1.07.

[0019] Example 9 The method for catalytic ring-opening polymerization of lactide using a tetranuclear cubane-configured zinc complex 2c at a catalyst-to-monomer molar ratio of 3000:1 is the same as in Example 7. The differences from Example 7 are: weighing of monomer (1.99 mmol) and zinc complex (0.00066 mmol), catalytic reaction time t = 35 s, monomer conversion conv. = 70%, polymer molecular weight Mn = 42.0 kg / mol, and polymer molecular weight distribution. Ð = 2.42.

[0020] Example 10 The method for catalytic ring-opening polymerization of lactide using a tetranuclear cubane zinc complex 2d at a catalyst-to-monomer molar ratio of 3000:1 is the same as in Example 7. The differences from Example 7 are: weighing of monomer (1.95 mmol) and zinc complex (0.00065 mmol), catalytic reaction time t = 70 s, monomer conversion conv. = 83%, polymer molecular weight Mn = 36.5 kg / mol, and polymer molecular weight distribution. Ð = 1.56.

[0021] Example 11 The method for catalytic ring-opening polymerization of lactide using a tetranuclear cubane zinc complex 2e at a catalyst-to-monomer molar ratio of 3000:1 is the same as in Example 7. The differences from Example 7 are: weighing of monomer (1.99 mmol) and zinc complex (0.00066 mmol), catalytic reaction time t = 49 s, monomer conversion conv. = 77%, polymer molecular weight Mn = 41.8 kg / mol, and polymer molecular weight distribution. Ð = 2.34.

[0022] Example 12 The method for catalytic ring-opening polymerization of lactide using a tetranuclear cubane-based zinc complex 2f at a catalyst-to-monomer molar ratio of 3000:1 is the same as in Example 7. The differences from Example 7 are: weighing of monomer (1.95 mmol) and zinc complex (0.00065 mmol), catalytic reaction time t = 80 s, monomer conversion conv. = 79%, polymer molecular weight Mn = 26.7 kg / mol, and polymer molecular weight distribution. Ð = 2.50.

[0023] Table 1 shows the various test data for the preparation of polylactide by the tetranuclear cubane-configured zinc complex 2a-2f catalyzing the ring-opening polymerization of lactide in the above embodiments. Table 1. Data for the preparation of polylactide from the tetranuclear cubane-configured zinc complexes 2a-2f at 130 °C via catalytic ring-opening polymerization of racemic lactide. Note: 1 Monomer conversion rate through 1 H-NMR spectroscopy determination.

[0024] 2 The molecular weight was determined by gel permeation chromatography (GPC) using polystyrene as a standard and tetrahydrofuran as the eluent.

[0025] 3 The formula for calculating the conversion frequency (TOF) is: TOF = conversion × ([monomer] / [initiator]) / time.

[0026] Table 1 shows that the tetranuclear cubane-configured β-ketoimine zinc complex prepared by this invention can catalyze the polymerization of lactide to prepare polylactide at 130 °C without the participation of a co-catalyst, and the monomer conversion rate is 70%~86%, which is significantly improved compared with the existing methods for catalyzing the polymerization of lactide to prepare polylactide. The catalyst preparation method is simple, the structure is novel, the zinc element is non-toxic, and it still has high catalytic activity under the condition of low catalyst dosage (catalyst to monomer molar ratio of 3000:1).

[0027] Among the six complexes, complex 2a exhibited the best catalytic effect. When the molar ratio of monomer to catalyst was 3000:1, a conversion rate of 86% could be achieved in 30 seconds, and the polymer molecular weight was 71.9 kg / mol.

[0028] The embodiments described above are merely preferred embodiments of the present invention, and not all feasible embodiments of the present invention. Any obvious modifications made by those skilled in the art without departing from the principles and spirit of the present invention should be considered to be included within the scope of protection of the claims of the present invention.

Claims

1. A zinc complex with a tetranuclear cubane configuration, characterized in that, The structure of the zinc complex with the tetranuclear cubane configuration is as shown in general formula I: Ⅰ Where R is -(CH2)4-, -CH(CH3)(CH2)2-, -( R )-CH(CH3)CH2-、-( S )-CH(CH3)CH2CH2-, -CH2CH(CH3)-, -( S Any one of )-CH2CH(CH3)-.

2. The method for preparing the tetranuclear cubane-type zinc complex as described in claim 1, characterized in that, Specifically, the following steps are included: Under inert gas protection, ZnEt2 was added dropwise to a solution of a β-ketoimine ligand with the structure of general formula II and reacted for 3–7 h at a temperature range of 40 ℃ to 90 ℃ to obtain the zinc complex with the tetranuclear cubane configuration; the structure of general formula II is as follows: Ⅱ Where R is -(CH2)4-, -CH(CH3)(CH2)2-, -( R )-CH(CH3)CH2-、-( S )-CH(CH3)CH2CH2-, -CH2CH(CH3)-, -( S Any one of )-CH2CH(CH3)-.

3. The method for preparing the tetranuclear cubane-type zinc complex according to claim 2, characterized in that, The molar ratio of the β-ketoimine ligand of general formula II to ZnEt2 is 1:0.8 to 1:1.

3.

4. The method for preparing the tetranuclear cubane-type zinc complex according to claim 2, characterized in that, The solvent in the β-ketoimine ligand solution of the structure as described in general formula II is one of toluene and tetrahydrofuran.

5. The method for preparing the tetranuclear cubane-type zinc complex according to claim 2, characterized in that, The solvent in the ZnEt2 solution is either toluene or n-hexane.

6. The method for preparing the tetranuclear cubane-type zinc complex according to claim 2, characterized in that, The inert gas is argon or nitrogen.

7. Application of the zinc complex with the tetranuclear cuboethane configuration as described in claim 1.

8. The application of the tetranuclear cubane-configured zinc complex according to claim 7, characterized in that, Specifically, it is used in the catalytic ring-opening polymerization of racemic lactide.

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