A binuclear N-alkoxy-β-ketimine lithium complex and its synthesis method and application

Abstract

The present invention belongs to the field of preparation and application of metal complex catalysts, and discloses a binuclear N-alkoxy-β-ketimine lithium complex and a synthesis method and application. The binuclear N-alkoxy-β-ketimine lithium complex is used to catalyze the ring-opening polymerization of lactide. The binuclear N-alkoxy-β-ketimine lithium complex is used as a catalyst, racemic lactide is used as a raw material, and in anhydrous and oxygen-free and inert gas argon protection, in tetrahydrofuran at 25°C, lactide ring-opening polymerization can be catalyzed to prepare polylactide without the participation of a co-catalyst. The catalyst has low toxicity, a simple preparation method, a novel structure, high catalytic activity, and a low catalyst dosage during the catalytic process.

Description

Technical Field

[0001] The invention belongs to the field of preparation and application of metal complex catalysts, and specifically relates to a binuclear N-alkoxy-β-ketoimine lithium complex and a preparation method thereof, and application thereof in catalyzing a lactide ring-opening polymerization reaction. Background Art

[0002] Polylactide (PLA) has broad technical application prospects in the biomedical and pharmaceutical fields due to its good biocompatibility and biodegradability. PLA has good tensile strength and ductility, and can be decomposed into carbon dioxide and water in the body, which makes it an ideal biomedical material. It can be used in drug delivery, surgical suture materials and artificial tissue materials, so it has great research potential. There are two existing methods for synthesizing PLA. The first method is lactic acid polycondensation, which uses microorganisms to ferment and purify plant starch to obtain lactic acid, and then dehydrates and polycondenses lactic acid under vacuum to obtain polylactide. A large number of practices have proved that the polymerization temperature of this method is harsh, and it is necessary to add coupling agents and adjuvants with high costs. The molecular weight distribution of the polylactide finally obtained is difficult to control and it is difficult to obtain high molecular weight polymers. The second method is lactide ring-opening polymerization, firstly, lactic acid is dehydrated to generate oligomers, then the oligomers are depolymerized into lactide, and finally lactide ring-opening polymerization is obtained to obtain polylactide. This method has the advantages of mild reaction conditions, high polymer molecular weight and controllable structure. Studies have shown that the ring-opening polymerization of lactide is more practical and efficient than the polycondensation of small molecule monomers. As long as a suitable catalyst is found, a high monomer conversion rate can be achieved under mild conditions to obtain high-performance polymers. In the process of lactide ring-opening polymerization, metal compounds are often used as catalysts to initiate monomer polymerization. (Polymer Reviews, 2008, 48, 11–63,)

[0003] At present, the industrial production of PLA is mainly through the ring-opening polymerization of lactide catalyzed by stannous octoate and stannous chloride. Studies have found that the polymers obtained by catalyzing lactide with metal catalysts contain some metal residues. The tin element itself is toxic and harmful to the human body, which will limit the application of PLA in the food and medical fields. Therefore, it is necessary to develop environmentally friendly metal catalysts to synthesize PLA with controllable molecular weight (Mn) and narrow molecular weight distribution. It is of great significance to realize the green and environmentally friendly process of producing polylactide. Summary of the invention

[0004] In order to overcome the shortcomings of the prior art, the present invention provides a binuclear N-alkoxy-β-ketoimine lithium complex and a synthesis method and application thereof. The binuclear N-alkoxy-β-ketoimine lithium complex is used as a catalyst, racemic lactide is used as a raw material, tetrahydrofuran is used as a solvent at 25°C in anhydrous and oxygen-free environment and under the protection of inert gas argon, and lactide ring-opening polymerization can be catalyzed to prepare polylactide without the participation of a co-catalyst.

[0005] The above object of the present invention is achieved through the following technical solutions:

[0006] A binuclear N-alkoxy-β-ketoimine lithium complex, wherein the binuclear N-alkoxy-β-ketoimine lithium complex has a structure as shown in general formula I:

[0007]

[0008] Where R 1 = any one of -CH3, -CF3, -C6H6, R 2 =-CH3, -C6H6, any one of them, R 3 = any one of -CH2CH2-, -CH2CH2CH2-.

[0009] Another object of the present invention is to provide a method for preparing the above binuclear N-alkoxy-β-ketoimine lithium complex, which specifically comprises the following steps:

[0010] In an argon environment, n-BuLi is slowly added dropwise to a β-ketoimine ligand solution of the general formula II at -78°C, and the reaction is completed by naturally warming to room temperature. The general formula II is as follows:

[0011]

[0012] Where R 1 = any one of -CH3, -CF3, -C6H6, R 2 =-CH3, -C6H6, any one of them, R 3 = any one of -CH2CH2-, -CH2CH2CH2-.

[0013] Furthermore, in the preparation method, the molar ratio of the β-ketimine ligand having a structure such as general formula II to n-BuLi is 1:0.9.

[0014] Furthermore, in the preparation method, the solvent in the β-ketimine ligand solution having a structure such as general formula II is toluene.

[0015] Furthermore, the solvent in the n-BuLi solution in the preparation method is n-hexane.

[0016] Another object of the present invention is to protect the use of binuclear N-alkoxy-β-ketoimine lithium complexes.

[0017] Furthermore, the application of the binuclear N-alkoxy-β-ketoimine lithium complex is specifically the application of the binuclear N-alkoxy-β-ketoimine lithium complex in catalyzing the ring-opening polymerization of lactide.

[0018] Compared with the prior art, the present invention has the following beneficial effects: the present invention develops a novel preparation method and application of a binuclear N-alkoxy-β-ketoimine lithium complex. With the binuclear N-alkoxy-β-ketoimine lithium complex as a catalyst and racemic lactide as a raw material, in anhydrous and oxygen-free and inert gas argon protection, in tetrahydrofuran at 25°C, lactide ring-opening polymerization can be catalyzed to prepare polylactide without the participation of a co-catalyst. The catalyst has low toxicity, a simple preparation method, a novel structure, high catalytic activity, and a low catalyst dosage during the catalytic process. The molecular weight distribution of the polymer obtained by the reaction is relatively narrow (1.5-1.6), and the molecular weight is controllable (25507-40586 g / mol). BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The present invention will be further described below in conjunction with the accompanying drawings and specific implementations.

[0020] Figure 1 Schematic diagram of the crystal structure of binuclear N-alkoxy-β-ketoimine lithium complex 2d. DETAILED DESCRIPTION

[0021] The present invention is described in detail below in conjunction with the examples. However, the following examples are only preferred implementations of the present invention, and the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field, within the technical scope disclosed in the present invention, shall make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention, which shall be covered within the protection scope of the present invention. The experimental methods adopted in the present invention are all conventional methods, and the experimental equipment, materials, reagents, etc. used can be obtained from commercial channels.

[0022] The reaction formula of the following embodiment is:

[0023]

[0024] Example 1

[0025] Synthesis of [CH3C(O)CHCN(CH2CH2CH2OCH3)CH3]2Li2(2a): In an argon environment, 1a (0.51 g, 3.0 mmol) was dissolved in anhydrous and oxygen-free toluene, the reaction tube was placed in a -78°C dry ice-ethanol bath, and n-butyl lithium (1.1 mL, 2.5 M in n-hexane, 2.7 mmol) was added dropwise. The reaction was stirred at -78°C and naturally warmed to room temperature to obtain a brown clear solution. The solvent was vacuum-dried and washed three times with 6 mL of n-hexane to obtain a light yellow powder, and the product was characterized by nuclear magnetic resonance and elemental analysis. Yield: 0.91 g (86%). 1H NMR (600MHz, DMSO-d6): δ=4.39(s,1H,[OC(CH)CN]),3.31(m,2H,CH2OCH3),3.19(s,3H,OCH3) ,3.11(m,2H,CNHCH2),1.73(m,2H,NHCH2CH2CH2),1.63(s,3H,CNCH3),1.62(s,3H,CH2OCH3). 13 C NMR (600MHz, DMSO-d6): δ=175.5,165.6,95.4,71.0,57.8,47.4,39.5,31.0,28.1,20.1.Anal.Calcd forC 18 H 32 Li2N2O4:C,61.01;H,9.10;N,7.91.Found:C,61.33;H,8.93;N,8.04.

[0026] Example 2

[0027] Synthesis of [CH3C(O)CHCN(CH2CH2OCH3)CH3]2Li2(2b): In an argon environment, 1b (0.47 g, 3.0 mmol) was dissolved in anhydrous and oxygen-free toluene, the reaction tube was placed in a -78°C dry ice-ethanol bath, n-butyl lithium (1.1 mL, 2.5 M in n-hexane, 2.7 mmol) was added dropwise, the reaction was stirred at -78°C and naturally warmed to room temperature to obtain a brown clear solution. The solvent was vacuum-dried, and the white powder was washed three times with 6 mL of cold n-hexane to obtain the white powder, and the product was characterized by nuclear magnetic resonance and elemental analysis. Yield: 0.42 g (43%). 1 H NMR(400MHz,Chloroform-d)δ=4.65(s,1H,[OC(CH)CN]),3.50(t,2H,CH2OCH3),3.38 -3.35(m,2H,CNHCH2),3.34(s,3H,OCH3),1.77(s,3H,CNCH3),1.76(s,3H,CH2OCH3). 13 C NMR (600MHz, Chloroform-d): δ=176.1,168.6,97.8,73.0,58.7,49.7,27.7,20.6.Anal.Calcd for C 16 H 28 Li2N2O4:C,58.90;H,8.65;N,8.59.Found:C,58.44;H,8.83;N,8.14.

[0028] Example 3

[0029] Synthesis of [C6H6C(O)CHCN(CH2CH2CH2OCH3)C6H6]2Li2(2c): In an argon environment, 1c (0.89 g, 3.0 mmol) was dissolved in anhydrous and oxygen-free toluene, the reaction tube was placed in a -78°C dry ice-ethanol bath, and n-butyl lithium (1.2 mL, 2.5 M in n-hexane, 3.0 mmol) was added dropwise. The reaction was stirred at -78°C and naturally warmed to room temperature to obtain a white turbid solution. The precipitate was filtered and washed three times with 6 mL of cold n-hexane to obtain a white powder, and the product was characterized by nuclear magnetic resonance and elemental analysis. Yield: 1.82 g (83%). 1 H NMR(600MHz,Chloroform-d)δ=7.80-7.20(m,10H,Ph-H),5.28(s,1H,[OC(CH)CN]),3.2 0(m,2H,CH2OCH3),3.14(m,2H,CNHCH2),3.12(s,3H,OCH3),1.49(m,2H,NHCH2CH2CH2). 13 C NMR (600MHz, Chloroform-d): δ=170.7,145.2,142.4,128.2,128.0,127.7,127.2,127.0,97.2,74.4,59.0,52.0,31.3.Anal.Calcd forC 38 H 40 Li2N2O4:C,75.74;H,6.69;N,4.65.Found:C,75.66;H,7.01;N,4.46.

[0030] Example 4

[0031] Synthesis of [CF3C(O)CHCN(CH2CH2CH2OCH3)CH3]2Li2(2d): In an argon environment, 1d (0.68 g, 3.0 mmol) was dissolved in anhydrous and oxygen-free toluene, the reaction tube was placed in a -78°C dry ice-ethanol bath, and n-butyl lithium (1.1 mL, 2.5 M in n-hexane, 2.7 mmol) was added dropwise. The reaction was stirred at -78°C and naturally warmed to room temperature to obtain a brown-yellow clear solution. The solvent was drained, and the powder was washed three times with 6 mL of n-hexane to obtain a yellow-brown powder, and the product was characterized by nuclear magnetic resonance and elemental analysis. Yield: 1.28 g (92%). 1H NMR(400MHz,Chloroform-d)δ=5.10(s,1H,[OC(CH)CN]),3.63(t,2H,CH2OCH3),3.38(m,2H,CNHCH2),3.33(s,3H,OCH3),1.96(m,2H,NHCH2CH2CH2),1.86(s,3H,CNCH3). 13 C NMR (400MHz, Chloroform-d): δ=168.1,158.4,95.3,74.8,59.3,50.9,30.3,20.7.Anal.Calcd for C 18 H 26 F6Li2N2O4:C,46.77;H,5.67;N,6.06.Found:C,46.43;H,6.01;N,5.86.

[0032] Example 5

[0033] Synthesis of [CF3C(O)CHCN(CH2CH2OCH3)CH3]2Li2(2e): In an argon environment, 1e (0.63 g, 3.0 mmol) was dissolved in anhydrous and oxygen-free toluene, the reaction tube was placed in a -78°C dry ice-ethanol bath, and n-butyl lithium (1.1 mL, 2.5 M in n-hexane, 2.7 mmol) was added dropwise. The reaction was stirred at -78°C and naturally warmed to room temperature to obtain a brown clear solution. The solvent was drained and washed three times with 6 mL of n-hexane to obtain a yellow-brown powder, and the product was characterized by nuclear magnetic resonance and elemental analysis. Yield: 1.30 g (93%). 1 H NMR(400MHz,Chloroform-d)δ=5.46(s,1H,[OC(CH)CN]),3.51(t,2H,CH2OCH3),3.41(m,2H,CNHCH2),3.33(s,3H,OCH3),1.88(s,3H,CNCH3). 13 CNMR(400MHz,Chloroform-d): δ=170.2,159.7,95.4,72.4,59.0,49.6,20.7,1.2.Anal.Calcd for C 16 H 22 F6Li2N2O4:C,44.26;H,5.11;N,6.45.Found:C,43.88;H,5.46;N,6.08.

[0034] Example 6

[0035] The binuclear N-alkoxy-β-ketoimine lithium complexes are catalyzed in a dehydrated and deoxygenated tetrahydrofuran solvent, the initial concentration of lactide is 1.0M, and the reaction temperature is 25°C. A method for catalyzing the ring-opening polymerization of lactide under the condition of a monomer to catalyst molar ratio of 300:1, the method comprising the following steps:

[0036] Under argon protection, a 0.01 mol / L catalyst solution of 2a was prepared using a dehydrated and deoxygenated tetrahydrofuran solution. The monomer (0.500 g) was accurately weighed and placed in 25°C IKA. 1.2 ml of the catalyst solution of 2a was added, and the mixture was stirred thoroughly and sampled at regular intervals. A small amount of sample was taken out with a syringe under argon protection, and the solvent was vacuum-evacuated. 1 H NMR (400MHz, CDCl3) was used to detect the conversion rate of lactide. It was found that 100% conversion could be achieved after 6 minutes of catalysis. After the catalysis, the bottle cap was opened directly to expose it to the air, the solvent was vacuumed, a small amount (1-2mL) of CH2Cl2 was added to fully dissolve the mixture, and then a large amount of cold methanol solution (-18°C) was added while vigorously stirring to allow the polymer to fully settle. The obtained crude polymer was repeatedly washed with cold methanol solution using a suction filtration device, and the residual solvent was pumped out using an oil pump at high temperature to obtain a pure polymer. The polymer molecular weight Mn = 34854 g / mol and molecular weight distribution were detected by GPC. At the same time, the homonuclear decoupled hydrogen spectrum of the polymer was measured, and the isotactic degree of the polymer was calculated using the formula to be Pm=0.39.

[0037] Example 7

[0038] A method for catalyzing the ring-opening polymerization of lactide by using binuclear N-alkoxy-β-ketimine lithium complex 2b at a monomer to catalyst molar ratio of 300:1 is the same as that in Example 6. The difference from Example 6 is that: catalytic reaction time t=5min, monomer conversion rate conv.=98%, polymer molecular weight Mn=31164g / mol, polymer molecular weight distribution The isotacticity of the polymer is Pm=0.38.

[0039] Example 8

[0040] A method for catalyzing the ring-opening polymerization of lactide using a binuclear N-alkoxy-β-ketimine lithium complex 2c at a monomer to catalyst molar ratio of 300:1 is the same as that in Example 6. The difference from Example 6 is that: the catalytic reaction time t=5min, the monomer conversion rate conv.=97%, the polymer molecular weight Mn=25507g / mol, and the polymer molecular weight distribution The isotacticity of the polymer is Pm=0.35.

[0041] Example 9

[0042] A method for catalyzing the ring-opening polymerization of lactide using a binuclear N-alkoxy-β-ketoimine lithium complex 2d at a monomer to catalyst molar ratio of 300:1, the method being the same as Example 6. The differences from Example 6 are as follows: catalytic reaction time t=2.5 min, monomer conversion rate conv.=95%, polymer molecular weight Mn=34067 g / mol, polymer molecular weight distribution The isotacticity of the polymer is Pm=0.29.

[0043] Example 10

[0044] A method for catalyzing the ring-opening polymerization of lactide using a binuclear N-alkoxy-β-ketimine lithium complex 2e at a monomer to catalyst molar ratio of 300:1, the method being the same as Example 6. The differences from Example 6 are: catalytic reaction time t=5 min, monomer conversion rate conv.=95%, polymer molecular weight Mn=34916 g / mol, polymer molecular weight distribution The isotacticity of the polymer is Pm=0.34.

[0045] Embodiment 11

[0046] A method for catalyzing the ring-opening polymerization of lactide using a binuclear N-alkoxy-β-ketoimine lithium complex 2d at a monomer to catalyst molar ratio of 1500:1, the method being the same as Example 6. The differences from Example 6 are as follows: catalytic reaction time t=26 min, monomer conversion rate conv.=95%, polymer molecular weight Mn=40586 g / mol, polymer molecular weight distribution The isotacticity degree of the polymer is Pm=0.31.

[0047] The test data of preparing polylactide by ring-opening polymerization of lactide catalyzed by binuclear N-alkoxy-β-ketimine lithium complexes 2a, 2b, 2c, 2d, and 2e in the above examples are shown in Table 1

[0048] Table 1 Data of preparation of polylactide by ring-opening polymerization of lactide catalyzed by binuclear N-alkoxy-β-ketimine lithium complex in tetrahydrofuran solution at 25°C

[0049]

[0050] Note: 1 The monomer conversion rate was 1 H NMR spectrum determination.

[0051] 2 The molecular weight is measured by gel permeation chromatography (GPC) using polystyrene as the standard substance and tetrahydrofuran as the eluent.

[0052] 3 The conversion frequency TOF calculation formula is: TOF = conversion × ([LA]: [Li]) / time.

[0053] 4 Pm represents the degree of isotacticity of the polymer, which is determined by homonuclear decoupling. 1 The results were confirmed by analysis of the methine region in the H NMR spectrum.

[0054] 5 Polymerization reaction conditions: [rac-LA]0 = 1.0 mol / L; Ar atmosphere.

[0055] It can be seen from Table 1 that the binuclear N-alkoxy-β-ketoimine lithium complex prepared by the present invention has a monomer conversion rate of 95% to 100% in the preparation of polylactide by catalyzing the polymerization of lactide at room temperature of 25° C., which is significantly improved compared with the existing method for catalyzing the polymerization of lactide to prepare polylactide. In addition, the binuclear N-alkoxy-β-ketoimine lithium complex prepared by the present invention can catalyze the polymerization of lactide to prepare polylactide without the participation of a co-catalyst. The catalyst preparation method is simple and the structure is novel. At 25° C., when the molar ratio of the monomer to the catalyst is 300:1, the complete conversion can be achieved in basically 5 minutes.

[0056] Among these five complexes, complex 1d has the best catalytic effect. When the molar ratio of monomer to catalyst is 300:1, 95% conversion can be achieved in 2.5 min of catalysis, and the conversion frequency TOF = 6840h -1 , polymer molecular weight Mn = 34067, polymer molecular weight distribution The polymer isotacticity Pm = 0.29. It exhibits the fastest catalytic rate, the narrowest molecular weight distribution, the lowest isotacticity, and the best stereoselectivity. Therefore, if 1d is continued to be selected as the catalyst, the catalyst dosage is reduced, and the molar ratio of monomer to catalyst is adjusted to 1500:1, the polymer molecular weight Mn can be increased to 40586.

[0057] The above-described embodiments are only preferred embodiments of the present invention, but not all feasible embodiments of the present invention. For those skilled in the art, any obvious changes made thereto without departing from the principles and spirit of the present invention should be considered to be included in the scope of protection of the claims of the present invention.

Claims

1. A binuclear N-alkoxy-β-ketoimine lithium complex, characterized in that: The binuclear N-alkoxy-β-ketoimine lithium complex has a structure as shown in general formula I: Where R 1 =-CH3, -CF 3、 -C6H6, any one, R 2 =-CH3, -C6H6, any one of them, R 3 = any one of -CH2CH2-, -CH2CH2CH2-.

2. The method for preparing the binuclear N-alkoxy-β-ketoimine lithium complex according to claim 1, characterized in that: The steps include: In an argon environment, n-BuLi is slowly added dropwise to a β-ketoimine ligand solution of the general formula II at a temperature of -78°C, and the reaction is completed by naturally warming to room temperature; the general formula II structure is as follows: Where R 1 =-CH3, -CF 3、 -C6H6, any one, R 2 =-CH3, -C6H6, any one of them, R 3 = any one of -CH2CH2-, -CH2CH2CH2-.

3. The method for preparing a binuclear N-alkoxy-β-ketoimine lithium complex according to claim 2, characterized in that: The molar ratio of the β-ketimine ligand of the general formula II to n-BuLi is 1:0.

9.

4. The method for preparing a binuclear N-alkoxy-β-ketoimine lithium complex according to claim 2, characterized in that: The solvent in the solution of the β-ketimine ligand having a structure such as general formula II is toluene.

5. The method for preparing a binuclear N-alkoxy-β-ketoimine lithium complex according to claim 2, characterized in that: The solvent in the n-BuLi solution is n-hexane.

6. Use of the binuclear N-alkoxy-β-ketoimine lithium complex as claimed in claim 1 in catalyzing the ring-opening polymerization of lactide.

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