A catalyst for synthesizing lactide from lactic acid, its preparation method and application

Abstract

The present invention provides a catalyst for synthesizing lactide from lactic acid, a preparation method thereof and an application thereof. The catalyst has a structure shown in formula (1), and has the characteristics of simple structure, easy availability of raw materials, simple synthesis, adjustable structure, etc. The central metal used is a non-toxic and pollution-free element such as calcium, magnesium, zinc, etc.; the alkoxy structure of the metal center can not only stabilize the metal center, but also serve as a polymerization initiation group to shorten the prepolymerization reaction time of lactic acid; the lactide synthesized by catalyzing the prepolymerization and depolymerization of lactic acid has high optical purity and low free lactic acid content.

Description

Technical Field

[0001] The present invention relates to a catalyst and a preparation method thereof, and an application of the catalyst in the process of synthesizing lactide from lactic acid. Background Art

[0002] At present, human society is facing the problems of serious white pollution and limited petroleum resources. Therefore, it is extremely urgent to vigorously develop renewable and degradable plastics. Among them, polylactic acid, as a popular biodegradable plastic, has excellent mechanical properties, chemical stability, biocompatibility and other advantages. Its raw material lactic acid is derived from renewable resources such as corn, and only water and carbon dioxide are generated after complete degradation, which is an environmentally friendly plastic.

[0003] There are two common methods for synthesizing polylactic acid. One is the direct dehydration condensation of lactic acid to form polylactic acid, but the water generated in the reaction system is difficult to remove, and the resulting polylactic acid often has a low molecular weight. The other is to first dehydrate and cyclize lactic acid to form a cyclic dimer lactide, and then catalytically ring-open polymerize lactide to obtain high-molecular-weight polylactic acid. The higher the chemical purity and optical purity of lactide, the better the performance and the wider the application of the polylactic acid obtained by catalytic polymerization.

[0004] At present, the industrial synthesis of lactide uses lactic acid as a raw material and metal salt catalysts (such as stannous octoate, stannous chloride, etc., see US5053522 for details). Tin has certain biological toxicity and is easy to contaminate products, and it is difficult to regenerate after the inactivation of such catalysts. Among zinc-based catalysts, zinc oxide (CN1616450) has good catalytic performance, but zinc oxide is a heterogeneous catalyst, which is difficult to be uniformly mixed with the lactic acid system and is easy to deposit at the bottom of the reactor, blocking the pipeline, which is not conducive to industrialization. It can be found from the published literature (CN101903370) that the content of free lactic acid in the currently industrially synthesized crude lactide is still relatively high, basically above 1.8%, and free lactic acid and lactic acid dimers directly affect the downstream polymerization application and need further purification treatment. If the content of lactic acid and lactic acid dimers in the crude lactide can be reduced, the synthesis steps can be reduced, the energy consumption can be reduced, and the synthesis process can be optimized. Summary of the Invention

[0005] In view of the above problems existing in the prior art, the present invention provides a catalyst for synthesizing lactide from lactic acid and a preparation method thereof. The catalyst is an organometallic complex containing aminopyridine and alkoxy structures, and has the characteristics of simple structure, easy availability of raw materials, simple synthesis, adjustable structure, etc. Among them, by adjusting the ligand substituents, the spatial environment and electronic effect of the metal center can be optimized, thereby improving the catalytic activity of the catalyst. The alkoxy structure connected to the metal active center not only plays a role in stabilizing the metal active center, but also can be used as a polymerization initiation group to shorten the pre-polymerization reaction time of lactic acid. In addition, compared with the existing complexes of this type, the catalyst of the present invention also has good hydrolysis resistance.

[0006] The present invention also provides a process for the polycondensation of lactic acid into polylactic acid and then the catalytic depolymerization to produce lactide using the above catalyst. The catalyst of the present invention uses non-toxic, pollution-free and biocompatible metals such as calcium, magnesium, and zinc as catalytic centers, and is combined with a ligand structure with adjustable structure, which can realize highly active catalysis of the pre-polymerization and depolymerization of lactic acid to produce lactide. The obtained lactide has high optical purity and low free lactic acid content.

[0007] The present invention provides a catalyst for synthesizing lactide from lactic acid, having the structure shown in formula (1):

[0008]

[0009] In the formula, R1 represents hydrogen, a linear, branched or cyclic alkyl group with 1 to 20 carbon atoms, a mono- or poly-aryl-substituted alkyl group with 7 to 30 carbon atoms, or a halogen; preferably a linear, branched or cyclic alkyl group with 1 to 10 carbon atoms, a mono- or poly-aryl-substituted alkyl group with 7 to 18 carbon atoms, or a halogen; more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, phenyl, benzyl, chlorine, bromine, iodine, etc.; further preferably methyl, ethyl, isopropyl, cyclohexyl;

[0010] R2 represents a linear, branched or cyclic alkyl group with 1 to 10 carbon atoms, a mono- or poly-aryl-substituted alkyl group with 7 to 30 carbon atoms; preferably a linear, branched or cyclic alkyl group with 1 to 8 carbon atoms, a mono- or poly-aryl-substituted alkyl group with 7 to 18 carbon atoms; more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, etc.; further preferably methyl, ethyl, isopropyl, cyclohexyl;

[0011] M is Mg, Ca or Zn, preferably Zn.

[0012] Preferably, the catalyst for synthesizing lactide from lactic acid is any one of the complexes shown in the following structural formulas [1]-

[16] :

[0013]

[0014] The present invention also provides a method for preparing a catalyst for the synthesis of lactide from lactic acid represented by formula (1), and the steps include:

[0015] 1) Mixing an amino-substituted aryl bromide, metallic magnesium, and solvent A to react to obtain an amino-substituted aryl magnesium bromide;

[0016] 2) Mixing the amino-substituted aryl magnesium bromide obtained in step 1), 2-bromopyridine, a catalyst, and solvent B to conduct a coupling reaction to obtain an amino-pyridine ligand;

[0017] 3) Mixing the amino-pyridine ligand obtained in step 2), a hexamethyldisilazane metal complex, and solvent C to conduct a coordination reaction, and then adding an alcohol compound to conduct an alkoxylation reaction to obtain a catalyst for the synthesis of lactide from lactic acid.

[0018] In step 1) of the present invention, the amino-substituted aryl bromide is selected from any one of the compounds having the structure shown in formula (2):

[0019]

[0020] In the formula, R1 is defined the same as R1 in formula (1), that is, R1 represents hydrogen, a linear, branched or cyclic alkyl group having 1 to 20 carbon atoms, a mono- or poly-aryl-substituted alkyl group having 7 to 30 carbon atoms, or a halogen; preferably a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms, a mono- or poly-aryl-substituted alkyl group having 7 to 18 carbon atoms, or a halogen; more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, phenyl, benzyl, chlorine, bromine, iodine, etc.; further preferably methyl, ethyl, isopropyl, cyclohexyl;

[0021] In step 1) of the present invention, the molar ratio of the amino-substituted aryl bromide to metallic magnesium is 1:1 - 2, preferably 1:1.2 - 1.3.

[0022] In step 1) of the present invention, the solvent A is selected from at least one of tetrahydrofuran and toluene, and preferably tetrahydrofuran;

[0023] The dosage of the solvent A is 1 - 15 mL per millimole of the amino-substituted aryl bromide.

[0024] In step 1) of the present invention, the amino-substituted aryl bromide is preferably added continuously in a dropping manner, and the feeding time is 30 - 60 min, preferably 30 min.

[0025] In step 1) of the present invention, for the reaction, the temperature is 30 - 60 °C, preferably 45 - 55 °C, and the time is 2 - 5 h, preferably 2 - 3 h;

[0026] Preferably, after the reaction is completed, a separation process is further included, which is a conventional operation in the art and has no special requirements. For example, after the reaction is completed, it is cooled to room temperature, allowed to stand for liquid separation, and the upper clear liquid is taken and the solvent is removed to obtain the amino-substituted arylmagnesium bromide.

[0027] In step 2) of the present invention, the molar ratio of the amino-substituted arylmagnesium bromide to 2-bromopyridine is 1:1 - 1.5, preferably 1:1 - 1.2.

[0028] In step 2) of the present invention, the catalyst is selected from 1,3-bis(diphenylphosphinopropane)nickel dichloride (NiCl2(dppp)2);

[0029] The dosage of the catalyst is 1 - 5% of the molar amount of the amino-substituted arylmagnesium bromide, preferably 2 - 3%.

[0030] In step 2) of the present invention, the solvent B is selected from at least one of tetrahydrofuran and toluene, preferably tetrahydrofuran;

[0031] The dosage of the solvent B is 1 - 15 mL per millimole of the amino-substituted arylmagnesium bromide.

[0032] In step 2) of the present invention, for the coupling reaction, the temperature is 0 - 20°C, preferably 0 - 5°C, and the time is 6 - 12 h, preferably 6 - 8 h.

[0033] In step 2) of the present invention, after the reaction is completed, a process of adding water for quenching and post-treatment is further included;

[0034] For the water addition for quenching, the added amount of water is 1 - 2 times the mass of the reaction system;

[0035] The post-treatment is a conventional operation in the art and has no special requirements. For example, in some examples, the preferred method adopted is that the quenched reaction solution is extracted with ethyl acetate, the organic phase is dried with Na2SO4, then filtered and concentrated under reduced pressure, and then purified by column chromatography with n-pentane / ethyl acetate and dried under vacuum to remove the solvent.

[0036] In step 3) of the present invention, the general formula of the hexamethyldisilylamine metal complex is M[N(SiMe3)2]2, where M represents a metal element, which has the same definition as M in formula (1), that is, selected from Mg, Ca or Zn, preferably Zn, and Me represents a methyl group.

[0037] The molar ratio of the hexamethyldisilylamine metal complex to the aminopyridine ligand is 1 - 1.5:1, preferably 1:1.

[0038] In step 3) of the present invention, the solvent C is selected from at least one of tetrahydrofuran and toluene, preferably tetrahydrofuran;

[0039] The dosage of the solvent C is 5 - 20 mL per millimole of the aminopyridine ligand.

[0040] In step 3) of the present invention, the general formula of the alcohol compound is R2OH, where R2 has the same definition as R2 in formula (1), that is, R2 represents a linear, branched or cyclic alkyl group with 1 - 10 carbon atoms, a mono- or poly-aryl-substituted alkyl group with 7 - 30 carbon atoms; preferably a linear, branched or cyclic alkyl group with 1 - 8 carbon atoms, a mono- or poly-aryl-substituted alkyl group with 7 - 18 carbon atoms; more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, etc.; further preferably methyl, ethyl, isopropyl, cyclohexyl;

[0041] The molar ratio of the alcohol compound to the aminopyridine ligand is 1 - 2:1, preferably 1.5:1.

[0042] In step 3) of the present invention, for the coordination reaction, the temperature is 10 - 50 °C, preferably 20 - 30 °C, and the time is 6 - 12 h, preferably 6 - 8 h;

[0043] For the alkoxylation reaction, the temperature is 10 - 50 °C, preferably 20 - 30 °C, and the time is 4 - 8 h, preferably 4 h;

[0044] In step 3) of the present invention, after the alkoxylation reaction is completed, it further includes a post-treatment process. The post-treatment is a conventional operation in the art and there is no special requirement. For example, filtration, solvent removal under reduced pressure, recrystallization, etc. can be used. Among them, the recrystallization solvent preferably uses a mixture of tetrahydrofuran and n-hexane with a volume ratio of 1:5.

[0045] In the preparation method of the present invention, correspondingly, the amino-substituted arylmagnesium bromide generated in step 1) and the aminopyridine ligand generated in step 2) are respectively compounds with the structures shown in formula (3) and formula (4):

[0046]

[0047] In formula (3) and formula (4), R1 is the same as R1 in formula (2).

[0048] The present invention also simultaneously provides a method for synthesizing lactide from lactic acid. The method uses an aqueous lactic acid solution as a raw material and, under the catalytic action of the above catalyst of the present invention, first undergoes a dehydration polycondensation reaction to generate a lactic acid oligomer, and then undergoes a high-temperature depolymerization reaction to generate lactide.

[0049] As a preference, the steps of the method for synthesizing lactide from lactic acid of the present invention include:

[0050] (1) Mix the aqueous lactic acid solution with a catalyst, and stir and react at an absolute pressure of 1 - 10 kPa, preferably 2 - 5 kPa, and a temperature of 20 - 50 °C, preferably 20 - 30 °C for 1 - 8 h, preferably 2 - 4 h. Then raise the temperature to 120 - 180 °C, preferably 150 - 180 °C, and stir and react for 3 - 10 h, preferably 3 - 4 h to dehydrate and polycondense lactic acid to form lactic acid oligomers with a molecular weight of 500 - 2000 Da.

[0051] (2) Stir and react the reaction system in step (1) at an absolute pressure of 1 - 4 kPa, preferably 1 - 2 kPa, and a temperature of 180 - 250 °C, preferably 200 - 230 °C for 1 - 4 h, preferably 1 h to depolymerize the lactic acid oligomers at high temperature to obtain lactide.

[0052] In step (1) of the present invention, the aqueous lactic acid solution has a concentration of 60 - 100 wt%, preferably 90 - 95 wt%.

[0053] The lactic acid is L-lactic acid and / or D-lactic acid with an optical purity > 99.5%.

[0054] In step (1) of the present invention, the mass ratio of the catalyst to the aqueous lactic acid solution is 1:100 - 5000, and the more preferred mass ratio is 1:500 - 1:2000.

[0055] In step (1) of the present invention, the rate of temperature increase is 0.5 - 2 °C / min, preferably 1 °C / min.

[0056] In steps (1) and (2) of the present invention, the stirring speed is 50 - 400 r / min, preferably 150 - 250 r / min.

[0057] The lactide prepared by the method of the present invention has an optical purity of not less than 96%, which can be as high as more than 98%, and the content of free lactic acid is less than 0.90 wt%, preferably as low as 0.21 wt%.

[0058] Compared with the prior art, the beneficial effects of the technical solution of the present invention are as follows:

[0059] The present invention designs a novel type of catalyst for the synthesis of lactide from lactic acid, specifically an alkoxymetal complex coordinated with aminopyridine. The catalyst of the present invention uses non-toxic, pollution-free, and biocompatible metals such as calcium, magnesium, and zinc, and has high catalytic activity for the polymerization of lactic acid and the depolymerization of lactic acid oligomers. The nitrogen atom on the aniline structure and the oxygen atom on the alkoxy structure in the ligand can form two covalent bonds with the metal active center. The metal ion obtains two shared electrons, and at the same time, the nitrogen atom on the pyridine structure coordinates with the metal center, and the shared electrons make the metal center more stable. Therefore, the catalyst exhibits good stability and solubility.

[0060] The alkoxy structure is connected to the metal active center of the catalyst of the present invention, and can be quickly replaced by the hydroxyl group of lactic acid during the catalytic reaction, greatly reducing the time required for the initiation reaction and improving the catalytic performance of the catalyst. At the same time, the alkoxy group is an electron-donating group, which can form a stable structure in the electron-deficient metal, further improving the stability and hydrolysis resistance of the catalyst. Detailed implementation mode

[0061] The present invention will be described in detail below through specific examples. The scope of the present invention is not limited to this specific implementation mode.

[0062] The sources of raw materials in the examples and comparative examples of the present invention are shown in the following table. Other reagent raw materials are all ordinary commercially available products unless otherwise specified.

[0063]

[0064] The test methods used in the examples and comparative examples of the present invention are as follows:

[0065] Hydrolysis resistance: Add 0.1 mL of pure water to the tested NMR tube and mix evenly, then retest. If the NMR result is the same as before, it proves that the complex has not hydrolyzed. If the NMR result changes, it proves that new substances are generated and the complex has hydrolyzed; test once every 24 hours and record the total time when hydrolysis occurs.

[0066] Stability: Place the tested NMR tube open to the air and test once every 24 hours. Compare the NMR results. If the NMR result is the same as before, it proves that the complex has not changed. If it is found that the NMR result changes, it proves that the structure of the complex has changed, and record the total time when the NMR result changes.

[0067] Optical purity: Weigh the lactide sample on an analytical balance, dissolve it with chromatographically pure acetonitrile, and analyze and detect the content of L-lactide by gas chromatography, which is the optical purity of the sample.

[0068] Free lactic acid content: Weigh the sample on an analytical balance, dissolve it with chromatographically pure acetonitrile, add HMDS and pyridine for derivatization, and then analyze and detect the content of lactic acid by gas chromatography.

[0069] Molecular weight test: Weigh the sample on an analytical balance, dissolve it with chromatographically pure tetrahydrofuran, filter it through a 0.45-micron organic filter, and then analyze and detect the molecular weight by gel permeation chromatography.

[0070] Gas chromatography: Use a DB-5 capillary column and a flame ionization detector. Under the conditions of a carrier gas flow rate of 1.5 mL / min, a split ratio of 30:1, an injection port temperature of 180 °C, a column temperature of 250 °C, and a detector chamber temperature of 180 °C, use the external standard method to qualitatively and quantitatively analyze the active ingredients.

[0071] Gel permeation chromatography: Using PS as the standard, adopting the method of connecting three columns of XT450, XT125, and XT45 in series, using chromatographically pure dichloromethane as the mobile phase, with a flow rate of 1 mL / min, a column temperature of 60 °C, and measuring at a flow cell temperature of 60 °C.

[0072] Example 1

[0073] 1) Synthesize 2-(N-methylaniline)magnesium bromide shown by the following formula:

[0074]

[0075] Add a magnetic stirrer and activated magnesium powder (0.316 g, 13 mmol) to a dry schlenk flask, and displace with nitrogen three times. Then, dropwise add 10 mL of an anhydrous THF solution of 2-bromo-N-methylaniline with a concentration of 1 mmol / mL within 30 min, and then react at 50 °C for 2 h. After the reaction is completed, cool to room temperature, let it stand for liquid separation, and take the upper clear liquid. After removing the solvent, it is 2-(N-methylaniline)magnesium bromide.

[0076] 2) Synthesize the methyl-substituted aminopyridine ligand A shown by the following formula:

[0077]

[0078] Mix 2-bromopyridine (1.58 g, 10 mmol), NiCl2(dppp)2 (108.41 g, 0.2 mmol) and 10 mL of anhydrous THF, then add 10 mmol of 2-(N-methylaniline)magnesium bromide prepared in step 1), and then react at 0 °C for 8 h. Add 20 mL of water to the reaction mixture to quench, extract with ethyl acetate, combine the organic phases, dry with Na2SO4, filter and concentrate under reduced pressure, and then purify by column chromatography with n-pentane / ethyl acetate, and dry under vacuum to obtain the methyl-substituted aminopyridine ligand A (1.676 g, yield 91%).

[0079] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.25 (dd, 1H), δ 8.37 (dd, 1H), δ 7.40 (dd, 1H), δ 7.38 (dd, 1H), δ 7.14 (dd, 1H), δ 7.03 (dd, 1H), δ 6.90 (dd, 1H), δ 6.85 (dd, 1H), δ 6.82 (m, 1H), δ 3.01 (s, 3H).

[0080] Example 2

[0081] 1) Synthesize 2-(N-ethylaniline)magnesium bromide shown by the following formula:

[0082]

[0083] A magnetic stir bar and activated magnesium powder (0.379 g, 15.6 mmol) were added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, a 10 mL anhydrous THF solution of 2-bromo-N-ethylaniline with a concentration of 1 mmol / mL was added dropwise within 30 min, and the reaction was carried out at 45 °C for 2.5 h. After the reaction was completed, it was cooled to room temperature, allowed to stand for liquid separation, and the upper clear liquid was taken. After removing the solvent, 2-(N-ethylaniline)magnesium bromide was obtained.

[0084] 2) Synthesis of the ethyl-substituted aminopyridine ligand B shown in the following formula:

[0085]

[0086] 2-Bromopyridine (1.74 g, 11 mmol), NiCl2(dppp)2 (108.41 g, 0.2 mmol) and 12 mL of anhydrous THF were mixed, and then 10 mmol of 2-(N-ethylaniline)magnesium bromide prepared in step 1) was added, and the reaction was carried out at 2 °C for 6 h. 20 mL of water was added to the reaction mixture to quench the reaction, and it was extracted with ethyl acetate. The combined organic phases were dried over Na2SO4, filtered and concentrated under reduced pressure, and then purified by column chromatography with n-pentane / ethyl acetate and dried in vacuo to obtain the ethyl-substituted aminopyridine ligand B (1.765 g, yield 89%).

[0087] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.28 (dd, 1H), δ 8.39 (dd, 1H), δ 7.42 (dd, 1H), δ 7.40 (dd, 1H), δ 7.16 (dd, 1H), δ 7.08 (dd, 1H), δ 6.90 (dd, 1H), δ 6.88 (dd, 1H), δ 6.80 (m, 1H), δ 3.45 (q, 2H), δ 1.28 (t, 3H).

[0088] Example 3

[0089] 1) Synthesis of 2-(N-cyclohexylaniline)magnesium bromide shown in the following formula:

[0090]

[0091] A stir bar and activated magnesium powder (0.316 g, 13 mmol) were added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, an anhydrous THF solution of 2-bromo-N-cyclohexylaniline (11 mL, 1 mmol / mL) was added dropwise over 30 min, and the reaction was carried out at 52 °C for 2 h. After the reaction was completed, the reaction mixture was cooled to room temperature, allowed to stand for liquid separation, and the upper clear liquid was taken. After removing the solvent, 2-(N-cyclohexylaniline)magnesium bromide was obtained.

[0092] 2) Synthesis of the cyclohexyl-substituted aminopyridine ligand C shown by the following formula:

[0093]

[0094] 2-Bromopyridine (2.05 g, 13 mmol), NiCl2(dppp)2 (108.41 g, 0.2 mmol), and 13 mL of anhydrous THF were mixed, and then 10 mmol of 2-(N-cyclohexylaniline)magnesium bromide prepared in step 1) was added. The reaction was carried out at 0 °C for 6 h. 20 mL of water was added to the reaction mixture to quench the reaction, and the mixture was extracted with ethyl acetate. The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. Then, column purification was carried out using n-pentane / ethyl acetate, and the product was dried under vacuum to obtain the cyclohexyl-substituted aminopyridine ligand C (2.221 g, yield 88%).

[0095] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.32 (dd, 1H), δ 8.40 (dd, 1H), δ 7.38 (dd, 1H), δ 7.36 (dd, 1H), δ 7.20 (dd, 1H), δ 7.01 (dd, 1H), δ 6.90 (dd, 1H), δ 6.86 (dd, 1H), δ 4.55 (s, 1H), δ 2.57 (m, 1H), δ 1.71 (m, 4H), δ 1.46 (m, 2H), δ 1.21 (m, 4H).

[0096] Example 4

[0097] Synthesis of the methyl-substituted methoxy zinc complex [1]:

[0098]

[0099] A magnetic stir bar was added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, Zn[N(SiMe3)2]2 (0.425 g, 1.1 mmol) and 11 mL of anhydrous THF were added and stirred until well mixed. Next, the methyl-substituted aminopyridine ligand A (0.184 g, 1 mmol) prepared in Example 1 was added, and the reaction was carried out at 28 °C for 7 h. Then, anhydrous methanol (0.048 g, 1.5 mmol) was added to the reaction solution, and the stirring reaction was continued at 25 °C for 5 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and the target product (0.185 g, yield 66%) was obtained by recrystallization with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5.

[0100] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.33 (dd, 1H), δ 8.43 (dd, 1H), δ 7.46 (dd, 1H), δ 7.44 (dd, 1H), δ 7.20 (dd, 1H), δ 7.09 (dd, 1H), δ 6.96 (dd, 1H), δ 6.91 (dd, 1H), δ 3.01 (s, 3H), δ 2.78 (s, 3H).

[0101] For the hydrolysis resistance test of complex [1], the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after being left open for 3 days, demonstrating that the complex prepared in this example has good hydrolysis resistance and stability.

[0102] Example 5

[0103] Synthesis of methyl-substituted ethoxy zinc complex [2]:

[0104]

[0105] A magnetic stir bar was added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, Zn[N(SiMe3)2]2 (0.502 g, 1.3 mmol) and 15 mL of anhydrous THF were added and stirred until well mixed. Next, the methyl-substituted aminopyridine ligand A (0.184 g, 1 mmol) prepared in Example 1 was added, and the reaction was carried out at 20 °C for 11 h. Then, anhydrous ethanol (0.055 g, 1.2 mmol) was added to the reaction solution, and the stirring reaction was continued at 30 °C for 4 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and the target product (0.185 g, yield 63%) was obtained by recrystallization with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5.

[0106] 11H NMR (400 MHz, CDCl3, 298 K) δ 9.30 (dd, 1H), δ 8.42 (dd, 1H), δ 7.45 (dd, 1H), δ 7.43 (dd, 1H), δ 7.19 (dd, 1H), δ 7.08 (dd, 1H), δ 6.95 (dd, 1H), δ 6.90 (dd, 1H), δ 3.57 (q, 2H), δ 2.78 (s, 3H), δ 1.10 (t, 3H).

[0107] For the hydrolysis resistance test of Complex [2], the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after being placed open to the air for 3 days, proving that the complex prepared in this example has good hydrolysis resistance and stability.

[0108] Example 6

[0109] Synthesize methyl-substituted isopropoxyzinc complex [3]:

[0110]

[0111] A magnetic stir bar was added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, Zn[N(SiMe3)2]2 (0.540 g, 1.4 mmol) and 15 mL of anhydrous THF were added and stirred to mix evenly. Next, the methyl-substituted aminopyridine ligand A (0.184 g, 1 mmol) prepared in Example 1 was added, and the reaction was carried out at 22 °C for 10 h. Then, anhydrous isopropanol (0.066 g, 1.1 mmol) was added to the reaction solution, and the stirring reaction was continued at 25 °C for 5 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and recrystallization was carried out with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.177 g, yield 58%).

[0112] 1 1H NMR (400 MHz, CDCl3, 298 K) δ 9.37 (dd, 1H), δ 8.56 (dd, 1H), δ 7.97 (dd, 1H), δ 7.51 (dd, 1H), δ 7.25 (dd, 1H), δ 7.00 (dd, 1H), δ 6.86 (dd, 1H), δ 6.69 (dd, 1H), δ 3.57 (q, 1H), δ 2.78 (s, 3H), δ 1.13 (t, 6H).

[0113] For the hydrolysis resistance test of Complex [3], the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after being placed open to the air for 3 days, proving that the complex prepared in this example has good hydrolysis resistance and stability.

[0114] Example 7

[0115] Synthesis of methyl-substituted n-butoxy zinc complex [4]:

[0116]

[0117] A magnetic stir bar was added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, Zn[N(SiMe3)2]2 (0.579 g, 1.5 mmol) and 16 mL of anhydrous THF were added and stirred until well mixed. Next, the methyl-substituted aminopyridine ligand A (0.184 g, 1 mmol) prepared in Example 1 was added, and the reaction was carried out at 30 °C for 10 h. Then, anhydrous n-butanol (0.089 g, 1.2 mmol) was added to the reaction solution, and the stirring reaction was continued at 25 °C for 6 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and the product was recrystallized with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.196 g, yield 61%).

[0118] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.37 (dd, 1H), δ 8.56 (dd, 1H), δ 7.97 (dd, 1H), δ 7.51 (dd, 1H), δ 7.25 (dd, 1H), δ 7.00 (dd, 1H), δ 6.86 (dd, 1H), δ 6.69 (dd, 1H), δ 3.53 (q, 2H), δ 2.78 (s, 3H), δ 1.53 (dd, 2H), δ 1.45 (dd, 2H), δ 0.90 (t, 3H).

[0119] For the hydrolysis resistance test of complex [4], the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after being placed open to the air for 3 days, indicating that the complex prepared in this example has good hydrolysis resistance and stability.

[0120] Example 8

[0121] Synthesis of ethyl-substituted phenoxy zinc complex [5]:

[0122]

[0123] A magnetic stir bar was added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, Zn[N(SiMe3)2]2 (0.386 g, 1 mmol) and 10 mL of anhydrous THF were added and stirred until well mixed. Next, the ethyl-substituted aminopyridine ligand B (0.198 g, 1 mmol) prepared in Example 2 was added, and the reaction was carried out at 20 °C for 12 h. Then, anhydrous phenol (0.122 g, 1.3 mmol) was added to the reaction solution, and the stirring reaction was continued at 20 °C for 5 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and the product was recrystallized with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.196 g, yield 55%).

[0124] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.33 (dd, 1H), δ 8.42 (dd, 1H), δ 7.45 (dd, 1H), δ 7.44 (dd, 1H), δ 7.25 (dd, 2H), δ 7.21 (dd, 1H), δ 7.09 (dd, 1H), δ 6.93 (dd, 1H), δ 6.91 (dd, 2H), δ 6.90 (dd, 1H), δ 6.88 (d, 1H), δ 3.10 (q, 2H), δ 1.14 (t, 3H).

[0125] For the hydrolysis resistance test of complex [5], the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after being placed open to the air for 3 days, proving that the complex prepared in this example has good hydrolysis resistance and stability.

[0126] Example 9

[0127] Synthesize ethyl-substituted cyclohexyloxy zinc complex [6]:

[0128]

[0129] A magnetic stir bar was added to a dry schlenk flask, and the flask was purged with nitrogen three times. Then, Zn[N(SiMe3)2]2 (0.463 g, 1.2 mmol) and 8 mL of anhydrous THF were added and stirred to mix evenly. Then, the ethyl-substituted aminopyridine ligand B (0.198 g, 1 mmol) prepared in Example 2 was added, and the reaction was carried out at 20 °C for 11 h. Then, anhydrous cyclohexanol (0.100 g, 1.5 mmol) was added to the reaction solution, and the stirring reaction was continued at 25 °C for 6 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and recrystallization was carried out with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.213 g, yield 59%).

[0130] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.32 (dd, 1H), δ 8.42 (dd, 1H), δ 7.44 (dd, 1H), δ 7.42 (dd, 1H), δ 7.20 (dd, 1H), δ 7.09 (dd, 1H), δ 6.92 (dd, 1H), δ 6.88 (dd, 1H), δ 3.54 (m, 1H), δ 3.10 (t, 2H), δ 1.72 (m, 2H), δ 1.57 (m, 4H), δ 1.47 (m, 2H), δ 1.44 (m, 2H), δ 1.14 (t, 3H).

[0131] For the hydrolysis resistance test of Complex [6], the NMR results remained unchanged after 24 h; for the stability test, the NMR results also remained unchanged after being placed open to the air for 3 days, indicating that the complex prepared in this example has excellent hydrolysis resistance and stability.

[0132] Example 10

[0133] Synthesis of cyclohexyl-substituted ethoxy zinc complex [7]:

[0134]

[0135] A magnetic stir bar was added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, Zn[N(SiMe3)2]2 (0.502 g, 1.3 mmol) and 12 mL of anhydrous THF were added and stirred to mix evenly. Subsequently, the cyclohexyl-substituted aminopyridine ligand C (0.252 g, 1 mmol) prepared in Example 3 was added, and the reaction was carried out at 28 °C for 8 h. Then, absolute ethanol (0.045 g, 1.4 mmol) was added to the reaction solution, and the stirring reaction was continued at 27 °C for 4 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and the target product was recrystallized with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.195 g, yield 54%).

[0136] 1 H NMR (400 MHz, CDCl3, 298 K) δ9.37 (dd, 1H), δ8.56 (dd, 1H), δ7.97 (dd, 1H), δ7.51 (dd, 1H), δ7.25 (dd, 1H), δ7.00 (dd, 1H), δ6.86 (dd, 1H), δ6.69 (dd, 1H), δ3.57 (dd, 2H), δ2.57 (m, 1H), δ1.71 (m, 4H), δ1.47 (m, 2H), δ1.11 (m, 4H), δ1.10 (t, 3H).

[0137] For the hydrolysis resistance test of Complex [7], the NMR results remained unchanged after 24 h; for the stability test, the NMR results also remained unchanged after being placed open to the air for 3 days, indicating that the complex prepared in this example has excellent hydrolysis resistance and stability.

[0138] Example 11

[0139] Synthesis of cyclohexyl-substituted isopropoxy zinc complex [8]:

[0140]

[0141] A magnetic stir bar was added to a dry Schlenk flask, which was purged with nitrogen three times. Then, Zn[N(SiMe3)2]2 (0.386 g, 1 mmol) and 5 mL of anhydrous THF were added and stirred until well mixed. Subsequently, the cyclohexyl-substituted aminopyridine ligand C (0.252 g, 1 mmol) prepared in Example 3 was added, and the reaction was carried out at 25 °C for 10 h. Then, anhydrous isopropanol (0.072 g, 1.2 mmol) was added to the reaction solution, and the stirring reaction was continued at 26 °C for 4 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and recrystallization was carried out with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.229 g, yield 61%).

[0142] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.37 (dd, 1H), δ 8.56 (dd, 1H), δ 7.97 (dd, 1H), δ 7.51 (dd, 1H), δ 7.25 (dd, 1H), δ 7.00 (dd, 1H), δ 6.86 (dd, 1H), δ 6.69 (dd, 1H), δ 3.57 (m, 1H), δ 2.57 (m, 1H), δ 1.71 (m, 4H), δ 1.47 (m, 2H), δ 1.11 (m, 4H), δ 1.13 (t, 6H).

[0143] For the hydrolysis resistance test of complex [8], the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after standing open for 3 days, which proved that the complex prepared in this example had good hydrolysis resistance and stability.

[0144] Example 12

[0145] Synthesis of methyl-substituted methoxymagnesium complex [9]:

[0146]

[0147] A magnetic stir bar was added to a dry Schlenk flask, which was purged with nitrogen three times. Then, Mg[N(SiMe3)2]2 (0.380 g, 1.1 mmol) and 10 mL of anhydrous THF were added and stirred until well mixed. Subsequently, the methyl-substituted aminopyridine ligand A (0.184 g, 1 mmol) prepared in Example 1 was added, and the reaction was carried out at 25 °C for 9 h. Then, anhydrous methanol (0.048 g, 1.5 mmol) was added to the reaction solution, and the stirring reaction was continued at 30 °C for 4 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and recrystallization was carried out with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.146 g, yield 61%).

[0148] 11H NMR (400 MHz, CDCl3, 298 K) δ 9.30 (dd, 1H), δ 8.40 (dd, 1H), δ 7.43 (dd, 1H), δ 7.40 (dd, 1H), δ 7.17 (dd, 1H), δ 7.06 (dd, 1H), δ 6.93 (dd, 1H), δ 6.88 (dd, 1H), δ 3.28 (s, 3H), δ 2.75 (s, 3H).

[0149] The hydrolysis resistance test of complex [9]: After 24 h, the NMR results did not change; the stability test: after standing open for 3 days, the NMR results also did not change, which proved that the complex prepared in this example had good hydrolysis resistance and stability.

[0150] Example 13

[0151] Synthesize methyl-substituted ethoxymagnesium complex

[10] :

[0152]

[0153] A magnetic stir bar was added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, Mg[N(SiMe3)2]2 (0.345 g, 1 mmol) and 13 mL of anhydrous THF were added and stirred to mix evenly. Next, the methyl-substituted aminopyridine ligand A prepared in Example 1 (0.184 g, 1 mmol) was added, and the reaction was carried out at 30 °C for 8 h. Then, absolute ethanol (0.069 g, 1.5 mmol) was added to the reaction solution, and the stirring reaction was continued at 25 °C for 6 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and the target product was recrystallized with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.119 g, yield 47%).

[0154] 1 1H NMR (400 MHz, CDCl3, 298 K) δ 9.35 (dd, 1H), δ 8.48 (dd, 1H), δ 7.40 (dd, 1H), δ 7.38 (dd, 1H), δ 7.10 (dd, 1H), δ 7.01 (dd, 1H), δ 6.90 (dd, 1H), δ 6.88 (dd, 1H), δ 3.54 (q, 2H), δ 2.76 (s, 3H), δ 1.12 (t, 3H).

[0155] The hydrolysis resistance test of complex

[10] : After 24 h, the NMR results did not change; the stability test: after standing open for 3 days, the NMR results also did not change, which proved that the complex prepared in this example had good hydrolysis resistance and stability.

[0156] Example 14

[0157] Synthesize methyl-substituted isopropoxymagnesium complex

[11] :

[0158]

[0159] A stir bar was added to a dry Schlenk flask, which was purged with nitrogen three times. Then, Mg[N(SiMe3)2]2 (0.518 g, 1.5 mmol) and 10 mL of anhydrous THF were added and stirred to mix evenly. Subsequently, the methyl-substituted aminopyridine ligand A prepared in Example 1 (0.184 g, 1 mmol) was added, and the reaction was carried out at 25 °C for 12 h. Then, anhydrous isopropanol (0.078 g, 1.3 mmol) was added to the reaction solution, and the stirring reaction was continued at 30 °C for 5 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and recrystallization was carried out with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.136 g, yield 51%).

[0160] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.37 (dd, 1H), δ 8.51 (dd, 1H), δ 7.95 (dd, 1H), δ 7.50 (dd, 1H), δ 7.25 (dd, 1H), δ 7.00 (dd, 1H), δ 6.86 (dd, 1H), δ 6.69 (dd, 1H), δ 3.57 (q, 1H), δ 2.72 (s, 3H), δ 1.13 (t, 6H).

[0161] For the hydrolysis resistance test of complex

[11] , the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after standing open for 3 days, demonstrating that the complex prepared in this example has good hydrolysis resistance and stability.

[0162] Example 15

[0163] Synthesis of methyl-substituted n-butoxymagnesium complex

[12]

[0164]

[0165] A stir bar was added to a dry Schlenk flask, which was purged with nitrogen three times. Then, Mg[N(SiMe3)2]2 (0.345 g, 1 mmol) and 11 mL of anhydrous THF were added and stirred to mix evenly. Subsequently, the methyl-substituted aminopyridine ligand A prepared in Example 1 (0.184 g, 1 mmol) was added, and the reaction was carried out at 30 °C for 8 h. Then, anhydrous n-butanol (0.089 g, 1.2 mmol) was added to the reaction solution, and the stirring reaction was continued at 28 °C for 4 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and recrystallization was carried out with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.185 g, yield 66%).

[0166] 11H NMR (400 MHz, CDCl3, 298 K) δ 9.37 (dd, 1H), δ 8.52 (dd, 1H), δ 7.94 (dd, 1H), δ 7.49 (dd, 1H), δ 7.25 (dd, 1H), δ 7.00 (dd, 1H), δ 6.86 (dd, 1H), δ 6.67 (dd, 1H), δ 3.50 (q, 2H), δ 2.77 (s, 3H), δ 1.53 (dd, 2H), δ 1.44 (dd, 2H), δ 0.91 (t, 3H).

[0167] For the hydrolysis resistance test of complex

[12] , the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after standing open for 3 days, demonstrating that the complex prepared in this example has good hydrolysis resistance and stability.

[0168] Example 16

[0169] Synthesis of ethyl-substituted phenoxymagnesium complex

[13] :

[0170]

[0171] A stir bar was added to a dry Schlenk flask, and it was purged with nitrogen three times. Then, Mg[N(SiMe3)2]2 (0.414 g, 1.2 mmol) and 10 mL of anhydrous THF were added and stirred to mix evenly. Subsequently, the ethyl-substituted aminopyridine ligand B (0.198 g, 1 mmol) prepared in Example 2 was added, and the reaction was carried out at 25 °C for 10 h. Then, anhydrous phenol (0.132 g, 1.4 mmol) was added to the reaction solution, and the stirring reaction was continued at 30 °C for 4 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and recrystallization was carried out with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.160 g, yield 51%).

[0172] 1 1H NMR (400 MHz, CDCl3, 298 K) δ 9.36 (dd, 1H), δ 8.47 (dd, 1H), δ 7.42 (dd, 1H), δ 7.40 (dd, 1H), δ 7.30 (dd, 2H), δ 7.20 (dd, 1H), δ 7.11 (dd, 1H), δ 6.90 (dd, 1H), δ 6.88 (dd, 2H), δ 6.85 (dd, 1H), δ 6.83 (d, 1H), δ 3.13 (q, 2H), δ 1.15 (t, 3H).

[0173] For the hydrolysis resistance test of complex

[13] , the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after standing open for 3 days, demonstrating that the complex prepared in this example has good hydrolysis resistance and stability.

[0174] Example 17

[0175] Synthesize ethyl-substituted cyclohexyloxymagnesium complex

[14] :

[0176]

[0177] A magnetic stir bar was added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, Mg[N(SiMe3)2]2 (0.414 g, 1.2 mmol) and 12 mL of anhydrous THF were added and stirred to mix evenly. Next, the ethyl-substituted aminopyridine ligand B (0.198 g, 1 mmol) prepared in Example 2 was added, and the reaction was carried out at 28 °C for 8 h. Then, anhydrous cyclohexanol (0.150 g, 1.5 mmol) was added to the reaction solution, and the stirring reaction was continued at 26 °C for 4 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and the target product was recrystallized with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.212 g, 66%).

[0178] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.35 (dd, 1H), δ 8.45 (dd, 1H), δ 7.45 (dd, 1H), δ 7.40 (dd, 1H), δ 7.25 (dd, 1H), δ 7.04 (dd, 1H), δ 6.90 (dd, 1H), δ 6.87 (dd, 1H), δ 3.50 (m, 1H), δ 3.12 (t, 2H), δ 1.75 (m, 2H), δ 1.60 (m, 4H), δ 1.48 (m, 2H), δ 1.45 (m, 2H), δ 1.13 (t, 3H).

[0179] For the hydrolysis resistance test of complex

[14] , the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after being placed open to the air for 3 days, which proved that the complex prepared in this example had good hydrolysis resistance and stability.

[0180] Example 18

[0181] Synthesize cyclohexyl-substituted ethoxymagnesium complex

[15] :

[0182]

[0183] A magnetic stir bar was added to a dry Schlenk flask, which was purged with nitrogen three times. Then, Mg[N(SiMe3)2]2 (0.345 g, 1 mmol) and 10 mL of anhydrous THF were added and stirred to mix evenly. Next, the cyclohexyl-substituted aminopyridine ligand C (0.252 g, 1 mmol) prepared in Example 3 was added, and the reaction was carried out at 25 °C for 8 h. Then, anhydrous ethanol (0.060 g, 1.3 mmol) was added to the reaction solution, and the stirring reaction was continued at 25 °C for 6 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and recrystallization was carried out with a tetrahydrofuran / n-hexane mixed solution with a volume ratio of 1:5 to obtain the target product (0.189 g, yield 59%).

[0184] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.37 (dd, 1H), δ 8.55 (dd, 1H), δ 7.95 (dd, 1H), δ 7.53 (dd, 1H), δ 7.25 (dd, 1H), δ 7.02 (dd, 1H), δ 6.84 (dd, 1H), δ 6.70 (dd, 1H), δ 3.57 (dd, 2H), δ 2.55 (m, 1H), δ 1.73 (m, 4H), δ 1.44 (m, 2H), δ 1.11 (m, 4H), δ 1.10 (t, 3H).

[0185] For the hydrolysis resistance test of complex

[15] , the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after standing open for 3 days, proving that the complex prepared in this example has good hydrolysis resistance and stability.

[0186] Example 19

[0187] Synthesis of cyclohexyl-substituted isopropoxymagnesium complex

[16] :

[0188]

[0189] A magnetic stir bar was added to a dry Schlenk flask, which was purged with nitrogen three times. Then, Mg[N(SiMe3)2]2 (0.345 g, 1 mmol) and 10 mL of anhydrous THF were added and stirred to mix evenly. Next, the cyclohexyl-substituted aminopyridine ligand C (0.252 g, 1 mmol) prepared in Example 3 was added, and the reaction was carried out at 25 °C for 8 h. Then, anhydrous isopropanol (0.090 g, 1.5 mmol) was added to the reaction solution, and the stirring reaction was continued at 25 °C for 4 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and recrystallization was carried out with a tetrahydrofuran / n-hexane mixed solution with a volume ratio of 1:5 to obtain the target product (0.211 g, yield 63%).

[0190] 11H NMR (400 MHz, CDCl3, 298 K) δ 9.37 (dd, 1H), δ 8.51 (dd, 1H), δ 7.94 (dd, 1H), δ 7.50 (dd, 1H), δ 7.25 (dd, 1H), δ 7.08 (dd, 1H), δ 6.80 (dd, 1H), δ 6.69 (dd, 1H), δ 3.54 (m, 1H), δ 2.57 (m, 1H), δ 1.73 (m, 4H), δ 1.47 (m, 2H), δ 1.13 (m, 4H), δ 1.10 (t, 6H).

[0191] The hydrolysis resistance test of complex

[16] : After 24 h, the NMR results did not change; the stability test: after being placed open to the air for 3 days, the NMR results also did not change, proving that the complex prepared in this example has good hydrolysis resistance and stability.

[0192] Example 20

[0193] Synthesis of lactide from lactic acid:

[0194] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 1 g of the methyl-substituted methoxy zinc complex [1] prepared in Example 9. Stir and react for 2 h in a nitrogen atmosphere at 25 °C and 4 kPaA, and then heat up to 120 °C at a rate of 2 °C / min and stir and react for 3 h to obtain a lactic acid oligomer with a molecular weight of 835 Da.

[0195] (2) Keep the absolute pressure of the reaction system in step (1) at 4 kPa, raise the temperature to 230 °C, react for 1 h, and then distill to obtain 536.3 g of white crystalline L-lactide, with a yield of 71%, an optical purity of 96.1%, and a free lactic acid content of 0.51 wt%.

[0196] Example 21

[0197] Synthesis of lactide from lactic acid:

[0198] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 1 g of the methyl-substituted methoxy zinc complex [2] prepared in Example 10. Stir and react for 2 h in a nitrogen atmosphere at 25 °C and 4 kPaA, and then heat up to 120 °C at a rate of 2 °C / min and stir and react for 3 h to obtain a lactic acid oligomer with a molecular weight of 805 Da.

[0199] (2) Keep the absolute pressure of the reaction system in step (1) at 4 kPa, raise the temperature to 220 °C, react for 1 h, and then distill to obtain 533.2 g of white crystalline L-lactide, with a yield of 71%, an optical purity of 96.6%, and a free lactic acid content of 0.53 wt%.

[0200] Example 22

[0201] Synthesis of lactide from lactic acid:

[0202] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) into a three-necked flask, and then add 1 g of [2] methyl-substituted ethoxy zinc complex. Stir and react for 2 h in a nitrogen atmosphere at 25 °C and 4000 PaA, and then heat up to 150 °C at a rate of 2 °C / min and stir and react for 3 h to obtain a lactic acid oligomer with a molecular weight of 1221 Da.

[0203] (2) Keep the absolute pressure of the reaction system in step (1) at 4000 Pa, raise the temperature to 230 °C, react for 1 h, and then distill to obtain 548.2 g of white crystalline L-lactide, with a yield of 73%, an optical purity of 96.5%, and a free lactic acid content of 0.34 wt%.

[0204] Example 23

[0205] Synthesis of lactide from lactic acid:

[0206] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) into a three-necked flask, and then add 1 g of [3] methyl-substituted isopropoxy zinc complex. Stir and react for 2 h in a nitrogen atmosphere at 25 °C and 4000 PaA, and then heat up to 180 °C at a rate of 2 °C / min and stir and react for 3 h to obtain a lactic acid oligomer with a molecular weight of 1645 Da.

[0207] (2) Keep the absolute pressure of the reaction system in step (1) at 4000 Pa, raise the temperature to 230 °C, react for 1 h, and then distill to obtain 534.8 g of white crystalline L-lactide, with a yield of 71%, an optical purity of 96.4%, and a free lactic acid content of 0.33 wt%.

[0208] Example 24

[0209] Synthesis of lactide from lactic acid:

[0210] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) into a three-necked flask, and then add 5 g of [4] methyl-substituted n-butoxy zinc complex. Stir and react for 2 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then heat up to 180 °C at a rate of 2 °C / min and stir and react for 3 h to obtain a lactic acid oligomer with a molecular weight of 1511 Da.

[0211] (2) Control the absolute pressure of the reaction system in step (1) to 3000 Pa, raise the temperature to 230 °C, react for 1 h, and then distill to obtain 571.5 g of white crystalline L-lactide, with a yield of 76%, an optical purity of 96.0%, and a free lactic acid content of 0.26 wt%.

[0212] Example 25

[0213] Synthesis of lactide from lactic acid:

[0214] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 10 g of [5] ethyl-substituted phenoxy zinc complex. Stir and react in a nitrogen atmosphere at 25 °C and 3000 PaA for 2 h, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 3 h to obtain a lactic acid oligomer with a molecular weight of 1475 Da.

[0215] (2) Control the absolute pressure of the reaction system in step (1) to 3000 Pa, raise the temperature to 230 °C, react for 1 h, and then distill to obtain 616.5 g of white crystalline L-lactide, with a yield of 82%, an optical purity of 95.1%, and a free lactic acid content of 0.31 wt%.

[0216] Example 26

[0217] Synthesis of lactide from lactic acid:

[0218] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 1 g of [6] ethyl-substituted cyclohexyloxy zinc complex. Stir and react in a nitrogen atmosphere at 25 °C and 3000 PAa for 3 h, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1642 Da.

[0219] (2) Control the reaction absolute pressure of the reaction system in step (1) to 2000 Pa, raise the temperature to 230 °C, react for 1 h, and then distill to obtain 581.3 g of white crystalline L-lactide, with a yield of 77%, an optical purity of 97.1%, and a free lactic acid content of 0.21 wt%.

[0220] Example 27

[0221] Synthesis of lactide from lactic acid:

[0222] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 1 g of [7] cyclohexyl-substituted ethoxy zinc complex. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1635 Da.

[0223] (2) Control the absolute pressure of the reaction system in step (1) to be 1000 Pa, raise the temperature to 230 °C, react for 1 h, and then distill to obtain 654.0 g of white crystalline L-lactide, with a yield of 87%, an optical purity of 97.5%, and a free lactic acid content of 0.65 wt%.

[0224] Example 28

[0225] Synthesis of lactide from lactic acid:

[0226] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 0.5 g of [8] cyclohexyl-substituted isopropoxy zinc complex. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1603 Da.

[0227] (2) Control the absolute pressure of the reaction system in step (1) to be 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 607.5 g of white crystalline L-lactide, with a yield of 81%, an optical purity of 97.7%, and a free lactic acid content of 0.90 wt%.

[0228] Example 29

[0229] Synthesis of lactide from lactic acid:

[0230] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 0.5 g of [9] methyl-substituted methoxy magnesium complex. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1610 Da.

[0231] (2) Control the absolute pressure of the reaction system in step (1) to be 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 585.8 g of white crystalline L-lactide, with a yield of 78%, an optical purity of 97.0%, and a free lactic acid content of 0.74 wt%.

[0232] Example 30

[0233] Synthesis of lactide from lactic acid:

[0234] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) into a three-necked flask, and then add 0.5 g of

[10] methyl-substituted ethoxymagnesium complex. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1609 Da.

[0235] (2) Control the absolute pressure of the reaction system in step (1) to be 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 572.2 g of white crystalline L-lactide, with a yield of 76%, an optical purity of 96.9%, and a free lactic acid content of 0.85 wt%.

[0236] Example 31

[0237] Synthesis of lactide from lactic acid:

[0238] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) into a three-necked flask, and then add 0.5 g of

[11] methyl-substituted isopropoxymagnesium complex. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1618 Da.

[0239] (2) Control the absolute pressure of the reaction system in step (1) to be 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 592.3 g of white crystalline L-lactide, with a yield of 79%, an optical purity of 96.6%, and a free lactic acid content of 0.86 wt%.

[0240] Example 32

[0241] Synthesis of lactide from lactic acid:

[0242] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) into a three-necked flask, and then add 0.5 g of

[12] methyl-substituted n-butoxymagnesium complex. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1622 Da.

[0243] (2) Control the absolute reaction pressure of the reaction system in step (1) to 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 630.2 g of white crystalline L-lactide, with a yield of 84%, an optical purity of 97.2%, and a free lactic acid content of 0.88 wt%.

[0244] Example 33

[0245] Synthesis of lactide from lactic acid:

[0246] (1) Add 1000 g of an aqueous solution of L-lactic acid (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 0.5 g of

[13] ethyl-substituted phenoxymagnesium complex. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1580 Da.

[0247] (2) Control the absolute reaction pressure of the reaction system in step (1) to 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 597.2 g of white crystalline L-lactide, with a yield of 79.6%, an optical purity of 97.7%, and a free lactic acid content of 0.83 wt%.

[0248] Example 34

[0249] Synthesis of lactide from lactic acid:

[0250] (1) Add 1000 g of an aqueous solution of L-lactic acid (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 0.5 g of

[14] ethyl-substituted cyclohexyloxymagnesium complex. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1660 Da.

[0251] (2) Control the absolute reaction pressure of the reaction system in step (1) to 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 642.3 g of white crystalline L-lactide, with a yield of 85.7%, an optical purity of 97.1%, and a free lactic acid content of 0.57 wt%.

[0252] Example 35

[0253] Synthesis of lactide from lactic acid:

[0254] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) into a three-necked flask, and then add 0.5 g of

[15] ethyl-substituted cyclohexyloxy magnesium complex. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1640 Da.

[0255] (2) Control the absolute pressure of the reaction system in step (1) to be 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 638.3 g of white crystalline L-lactide, with a yield of 85.1%, an optical purity of 97.9%, and a free lactic acid content of 0.61 wt%.

[0256] Example 36

[0257] Synthesis of lactide from lactic acid:

[0258] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) into a three-necked flask, and then add 0.5 g of

[16] ethyl-substituted cyclohexyloxy magnesium complex. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 PaA, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 4 h to obtain a lactic acid oligomer with a molecular weight of 1550 Da.

[0259] (2) Control the absolute pressure of the reaction system in step (1) to be 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 666.3 g of white crystalline L-lactide, with a yield of 88.8%, an optical purity of 97.7%, and a free lactic acid content of 0.69 wt%.

[0260] Comparative Example 1

[0261] 1) Synthesize 2-(2-hydroxyethyl)magnesium bromide shown in the following formula:

[0262]

[0263] Add a magnetic stir bar and activated magnesium powder (0.316 g, 13 mmol) into a dry schlenk flask, and displace with nitrogen three times. Then, dropwise add 10 mL of an anhydrous THF solution of 1-(2-bromophenyl)ethanol with a concentration of 1 mol / L within 30 min, and then react at 60 °C for 3 h. After the reaction is completed, cool to room temperature, let it stand for liquid separation, and take the upper clear liquid. After removing the solvent, it is 2-(2-hydroxyethyl)magnesium bromide.

[0264] 2) Synthesize 2-hydroxyethyl-substituted aminopyridine ligand I shown in the following formula:

[0265]

[0266] Mix 2-bromopyridine (1.58 g, 10 mmol), NiCl2(dppp)2 (108.41 g, 0.2 mmol) and 10 mL of anhydrous THF, then add 0.01 mol of 2-(2-hydroxyethyl)magnesium bromide prepared in step 1), and then react at 5 °C for 6 h. Add 20 mL of water to quench the reaction mixture, extract with ethyl acetate, combine the organic phases, dry over Na2SO4, filter and concentrate under reduced pressure, and then purify by column chromatography with n-pentane / ethyl acetate, and dry in vacuo to obtain the 2-hydroxyethyl-substituted aminopyridine ligand I (1.791 g, yield 90%).

[0267] 1 H NMR (400 MHz, CDCl3, 298 K) δ 8.37 (d, 1H), δ 8.05 (d, 1H), δ 7.47 (dd, 1H), δ 7.43 (dd, 1H), δ 7.38 (dd, 1H), δ 7.34 (dd, 1H), δ 7.14 (dd, 1H), δ 6.90 (dd, 1H), δ 5.17 (s, 1H), δ 4.98 (td, 1H), δ 1.49 (d, 3H).

[0268] 3) Synthesis of 2-hydroxyethyl zinc methoxide complex

[17] :

[0269]

[0270] Add a stir bar to a dry schlenk flask, displace with nitrogen three times, then add Zn[N(SiMe3)2]2 (0.425 g, 1.1 mmol) and 13 mL of anhydrous THF and stir to mix evenly. Then add the 2-hydroxyethyl-substituted aminopyridine ligand I (0.199 g, 1 mmol) prepared in step 2), react at 25 °C for 7 h, and then add anhydrous methanol (0.048 g, 1.5 mmol) to the reaction solution and continue to stir and react at 25 °C for 5 h. Filter to remove impurities, remove the solvent under reduced pressure, and recrystallize with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.204 g, yield 69%).

[0271] 1 H NMR (400 MHz, CDCl3, 298 K) δ 8.56 (dd, 1H), δ 8.05 (dd, 1H), δ 7.82 (dd, 1H), δ 7.47 (dd, 1H), δ 7.43 (dd, 1H), δ 7.38 (dd, 1H), δ 7.34 (dd, 1H), δ 6.95 (dd, 1H), δ 4.98 (td, 1H), δ 3.39 (s, 3H), δ 1.49 (s, 3H).

[0272] For the hydrolysis resistance test of the complex

[17] , the NMR results changed after 1 h, and hydrolysis products were formed; for the stability test, the NMR results changed after standing open for 1 h, and new substances were produced.

[0273] 4) Synthesis of lactide from lactic acid:

[0274] (1) Add 1000 g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 0.5 g of the methoxy zinc complex of

[17] 2-hydroxyethyl. Stir and react for 3 h in a nitrogen atmosphere at 25 °C and 3000 Pa, and then heat up to 180 °C at a rate of 2 °C / min and stir and react for 6 h to obtain only a lactic acid oligomer with a molecular weight of 800 Da.

[0275] (2) Control the absolute pressure of the reaction system in step (1) to be 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 361.5 g of white crystalline L-lactide, with a yield of 48.2%, an optical purity of 95.5%, and a free lactic acid content of 33.5 wt%.

[0276] Comparative Example 2

[0277] 1) Synthesis of 2-(N-methylaniline) magnesium bromide shown by the following formula:

[0278]

[0279] Add a stir bar and active magnesium powder (0.316 g, 13 mmol) to a dry schlenk flask, and displace with nitrogen three times. Then, dropwise add 10 mL of an anhydrous THF solution of 1 mol / L 2-bromo-N-methylaniline within 30 min, and then react at 50 °C for 2 h. After the reaction, cool to room temperature, let it stand for liquid separation, and take the upper clear liquid. After removing the solvent, it is 2-(N-methylaniline) magnesium bromide.

[0280] 2) Synthesis of the methyl-substituted amino 2-phenyl ligand J shown by the following formula:

[0281]

[0282] Mix bromobenzene (1.57 g, 10 mmol), NiCl2(dppp)2 (108.41 g, 0.2 mmol) and 10 mL of anhydrous THF, then add 0.01 mol of 2-(N-methylaniline) magnesium bromide prepared in step 1), and then react at 2 °C for 8 h. Add 20 mL of water to quench the reaction mixture, extract with ethyl acetate, combine the organic phases, dry with Na2SO4, filter and concentrate under reduced pressure, and then purify by column chromatography with n-pentane / ethyl acetate and dry under vacuum to obtain the methyl-substituted amino 2-phenyl ligand J (1.665 g, yield 91%).

[0283] 1 H NMR (400 MHz, CDCl3, 298 K) δ 8.04 (dd, 1H), δ 7.40 - 7.43 (m, 4H), δ 7.08 (dd, 2H), δ 7.03 (dd, 1H), δ 6.90 (t, 1H), δ 6.82 (s, 1H), δ 3.01 (s, 3H).

[0284] 3) Synthesis of methyl - substituted methoxy zinc complex

[18] :

[0285]

[0286] A stir bar was added to a dry Schlenk flask, and the flask was purged with nitrogen three times. Then, Zn[N(SiMe3)2]2 (0.425 g, 1.1 mmol) and 15 mL of anhydrous THF were added and stirred to mix evenly. Next, the methyl - substituted amino - 2 - phenyl ligand A (0.183 g, 1 mmol) prepared in step 2 was added, and the reaction was carried out at 28 °C for 7 h. Then, anhydrous methanol (0.048 g, 1.5 mmol) was added to the reaction solution, and the stirring reaction was continued at 25 °C for 5 h. The impurities were removed by filtration, the solvent was removed under reduced pressure, and recrystallization was carried out with a mixed solution of tetrahydrofuran / n - hexane with a volume ratio of 1:5 to obtain the target product (0.184 g, yield 66%).

[0287] 1 H NMR (400 MHz, CDCl3, 298 K) δ 8.04 (dd, 1H), δ 7.41 - 7.43 (m, 3H), δ 7.33 (t, 1H), δ 7.08 (dd, 2H), δ 6.86 - 6.90 (dd, 2H), δ 3.39 (s, 3H), δ 2.78 (s, 3H).

[0288] For the hydrolysis resistance test of complex

[18] , the 1H NMR results changed after 1 h, and hydrolysis products were formed; for the stability test, the 1H NMR results changed after standing open to the air for 1 h, and new substances were produced.

[0289] 4) Synthesis of lactide from lactic acid:

[0290] (1) 1000 g of aqueous L - lactic acid solution (90 wt%, optical purity > 99.5%) was added to a three - necked flask, and then 0.5 g of the

[18] methyl - substituted methoxy zinc complex was added. The reaction was stirred at 25 °C in a nitrogen atmosphere of 3000 PaA for 3 h, and then the temperature was raised to 180 °C at a rate of 2 °C / min and stirred for 8 h, only obtaining a lactic acid oligomer with a molecular weight of 560 Da.

[0291] (2) Control the absolute pressure of the reaction system in step (1) to 1000 PaA, raise the temperature to 200 °C, react for 1 h, and then distill to obtain 311.3 g of white crystalline L-lactide, with a yield of 41.5%, an optical purity of 94.6%, and a free lactic acid content of 46.5 wt%.

[0292] Comparative Example 3

[0293] 1) The ligand synthesis step is the same as in Example 1.

[0294] 2) Synthesize the methyl-substituted silylamino zinc complex

[19] :

[0295]

[0296] Add a stir bar to a dry schlenk flask, displace with nitrogen three times, then add Zn[N(SiMe3)2]2 (0.425 g, 1.1 mmol) and 11 mL of anhydrous THF and stir to mix evenly. Then add the methyl-substituted aminopyridine ligand A (0.184 g, 1 mmol) prepared in Example 1 and react at 30 °C for 6 h. Filter to remove impurities, remove the solvent under reduced pressure, and recrystallize with a mixed solution of tetrahydrofuran / n-hexane with a volume ratio of 1:5 to obtain the target product (0.323 g, yield 76%).

[0297] 1 H NMR (400 MHz, CDCl3, 298 K) δ 9.25 (dd, 1H), δ 8.56 (dd, 1H), δ 7.82 (dd, 1H), δ 7.33 - 7.38 (m, 2H), δ 6.95 (t, 1H), δ 6.85 - 6.86 (dd, 2H), δ 2.78 (s, 3H), δ 0.08 (s, 18H).

[0298] For the hydrolysis resistance test of complex

[19] , the NMR results changed after 1 h and hydrolysis products were formed; for the stability test, the NMR results changed after standing open for 1 h and new substances were produced.

[0299] Synthesize lactide from lactic acid:

[0300] (1) Add 1000 g of an aqueous solution of L-lactic acid (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 0.5 g of the methyl-substituted silylamino zinc complex

[19] . Stir and react in a nitrogen atmosphere at 25 °C and 3000 Pa for 3 h, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 24 h to obtain only a lactic acid oligomer with a molecular weight of 200 Da.

[0301] (2) Control the absolute reaction pressure of the reaction system in step (1) to 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill. Only a small amount of white crystalline L-lactide, 22.1 g, is obtained, with a yield of 2.9%, an optical purity of 93.5%, and a free lactic acid content of 66.5 wt%.

[0302] Comparative Example 4

[0303] Synthesis of lactide from lactic acid:

[0304]

[0305] For the hydrolysis resistance test of complex

[20] , the NMR results did not change after 24 h; for the stability test, the NMR results also did not change after being left open for 3 days, proving that the complex prepared in this example has good hydrolysis resistance and stability.

[0306] (1) Add 1000 g of aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 0.5 g of

[20] methyl-substituted methoxy copper complex. Stir and react in a nitrogen atmosphere at 25 °C and 3000 PaA for 3 h, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 8 h to obtain only a lactic acid oligomer with a molecular weight of 600 DaA.

[0307] (2) Control the absolute reaction pressure of the reaction system in step (1) to 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill. Only a small amount of white crystalline L-lactide, 62.1 g, is obtained, with a yield of 8.3%, an optical purity of 94.1%, and a free lactic acid content of 35.1 wt%.

[0308] Comparative Example 5

[0309] Synthesis of lactide from lactic acid:

[0310]

[0311] For the hydrolysis resistance test of complex

[21] , the NMR results changed after 1 h, and hydrolysis products were formed; for the stability test, the NMR results changed after being left open for 1 h, and new substances were produced.

[0312] (1) Add 1000 g of aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) to a three-necked flask, and then add 0.5 g of

[21] bis(2-pyridyl)methyl-substituted aminophenoxymagnesium complex (prepared according to the method of CN108558932A). Stir and react in a nitrogen atmosphere at 25 °C and 3000 Pa for 3 h, and then raise the temperature to 180 °C at a rate of 2 °C / min and stir and react for 24 h to obtain only a lactic acid oligomer with a molecular weight of 180 Da.

[0313] (2) Control the absolute reaction pressure of the reaction system in step (1) to 1000 Pa, raise the temperature to 200 °C, react for 1 h, and then distill. Only a small amount of white crystalline L-lactide, 18.8 g, is obtained, with a yield of 2.5%, an optical purity of 94.6%, and a free lactic acid content of 65.1 wt%.

Claims

1. A catalyst for synthesizing lactide from lactic acid, characterized in that, It has the structure shown in formula (1): In the formula, R1 represents an alkyl group with a straight-chain, branched-chain or cyclic structure having 1 to 10 carbon atoms; R2 represents an alkyl group with a straight-chain, branched-chain or cyclic structure having 1 to 10 carbon atoms; M is Mg, Ca or Zn.

2. The catalyst for synthesizing lactide from lactic acid according to claim 1, wherein R1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl; R2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl.

3. The catalyst for synthesizing lactide from lactic acid according to claim 2, characterized in that, R1 is methyl, ethyl, isopropyl, cyclohexyl; R2 is methyl, ethyl, isopropyl, cyclohexyl.

4. The catalyst for synthesizing lactide from lactic acid according to claim 1, wherein The catalyst for synthesizing lactide from lactic acid is any one of the complexes shown in the following structural formulas [1]-[4], [6]-[12], [14]-[16]:

5. A method for preparing a catalyst for synthesizing lactide from lactic acid according to any one of claims 1-4, characterized in that the steps Including: 1) Mix an amino-substituted aryl bromide, metallic magnesium, and solvent A and react to obtain an amino-substituted arylmagnesium bromide; 2) Mix the amino-substituted arylmagnesium bromide obtained in step 1), 2-bromopyridine, a catalyst, and solvent B and conduct a coupling reaction to obtain an aminopyridine ligand; 3) Mix the aminopyridine ligand obtained in step 2), a hexamethyldisilylamine metal complex, and solvent C and conduct a coordination reaction, and then add an alcohol compound to conduct an alkoxylation reaction to obtain a catalyst for synthesizing lactide from lactic acid; In step 1), the solvent A is selected from at least one of tetrahydrofuran and toluene; the amino-substituted aryl bromide is selected from any one of the compounds having the structure shown in formula (2): In the formula, the definition of R1 is the same as that of R1 in formula (1); In step 2), the catalyst is selected from 1,3-bis(diphenylphosphine propane) nickel dichloride; the solvent B is selected from at least one of tetrahydrofuran and toluene; In step 3), the general formula of the hexamethyldisilylamine metal complex is M[N(SiMe3)2]2, where M represents a metal element, and the definition is the same as that of M in formula (1), and Me represents methyl; the solvent C is selected from at least one of tetrahydrofuran and toluene; the general formula of the alcohol compound is R2OH, where the definition of R2 is the same as that of R2 in formula (1).

6. The preparation method according to claim 5, characterized in that In step 1), the molar ratio of the amino-substituted aryl bromide to metallic magnesium is 1:1 - 2; In step 1), the solvent A is tetrahydrofuran; The dosage of the solvent A is 1 - 15 mL per millimole of the amino-substituted aryl bromide; In step 1), the amino-substituted aryl bromide is added continuously, and the feeding time is 30 - 60 min; In step 1), for the reaction, the temperature is 30 - 60 °C and the time is 2 - 5 h.

7. The preparation method according to claim 6, characterized in that, In step 1), the amino-substituted aryl bromide is added dropwise.

8. The preparation method according to claim 6, characterized in that, The molar ratio of the amino-substituted aryl bromide to metallic magnesium is 1:1.2 - 1.

3.

9. The preparation method according to claim 6, characterized in that, For the reaction, the temperature is 45 - 55 °C and the time is 2 - 3 h.

10. The preparation method according to claim 5, characterized in that, In step 2), the molar ratio of the amino-substituted arylmagnesium bromide to 2-bromopyridine is 1:1 - 1.5; In step 2), the dosage of the catalyst is 1 - 5% of the molar amount of the amino-substituted arylmagnesium bromide; In step (2), the solvent B is tetrahydrofuran; The amount of the solvent B used is 1 - 15 mL per millimole of amino-substituted arylmagnesium bromide; In step (2), for the coupling reaction, the temperature is 0 - 20 °C and the time is 6 - 12 h; In step (2), after the reaction is completed, it further includes a process of quenching with water; For the quenching with water, the amount of water added is 1 - 2 times the mass of the reaction system.

11. The preparation method according to claim 10, characterized in that, The molar ratio of the amino-substituted arylmagnesium bromide to 2-bromopyridine is 1:1 - 1.

2.

12. The preparation method according to claim 10, wherein The amount of the catalyst used is 2 - 3% of the molar amount of the amino-substituted arylmagnesium bromide.

13. The preparation method according to claim 10, characterized in that, For the coupling reaction, the temperature is 0 - 5 °C and the time is 6 - 8 h.

14. The preparation method according to claim 5, characterized in that, In step (3), the molar ratio of the hexamethyldisilylamine metal complex to the aminopyridine ligand is 1 - 1.5:1; In step (3), the solvent C is tetrahydrofuran; The amount of the solvent C used is 5 - 20 mL per millimole of the aminopyridine ligand; In step (3), the molar ratio of the alcohol compound to the aminopyridine ligand is 1 - 2:1; In step (3), for the coordination reaction, the temperature is 10 - 50 °C and the time is 6 - 12 h; For the alkoxylation reaction, the temperature is 10 - 50 °C and the time is 4 - 8 h.

15. The preparation method according to claim 14, wherein The molar ratio of the alcohol compound to the aminopyridine ligand is 1.5:

1.

16. The preparation method according to claim 14, characterized in that, For the coordination reaction, the temperature is 20 - 30 °C and the time is 6 - 8 h.

17. The preparation method according to claim 14, characterized in that, For the alkoxylation reaction, the temperature is 20 - 30 °C and the time is 4 h.

18. A method for synthesizing lactide from lactic acid, characterized in that, The method uses an aqueous lactic acid solution as a raw material, and under the action of the catalyst described in any one of claims 1 - 4 or the catalyst prepared by the preparation method described in any one of claims 5 - 17, first undergoes a dehydration polycondensation reaction to generate lactic acid oligomers, and then undergoes a high-temperature depolymerization reaction to generate lactide.

19. The method according to claim 18, wherein the step It includes: (1) Mix the aqueous lactic acid solution with the catalyst, and stir and react at an absolute pressure of 1 - 10 kPa and a temperature of 20 - 50 °C for 1 - 8 h, and then raise the temperature to 120 - 180 °C and stir and react for 3 - 10 h to dehydrate and polycondense lactic acid to generate lactic acid oligomers with a molecular weight of 500 - 2000 Da; (2) Stir and react the reaction system in step (1) at an absolute pressure of 1 - 4 kPa and a temperature of 180 - 250 °C for 1 - 4 h to depolymerize the lactic acid oligomers at high temperature to obtain lactide.

20. The method according to claim 19, characterized in that the step It includes: (1) Mix the aqueous lactic acid solution with the catalyst, and stir and react at an absolute pressure of 2 - 5 kPa and a temperature of 20 - 30 °C for 2 - 4 h, and then raise the temperature to 150 - 180 °C and stir and react for 3 - 4 h to dehydrate and polycondense lactic acid to generate lactic acid oligomers with a molecular weight of 500 - 2000 Da; (2) Stir and react the reaction system in step (1) at an absolute pressure of 1 - 2 kPa and a temperature of 200 - 230 °C for 1 h to depolymerize the lactic acid oligomers at high temperature to obtain lactide.

21. The method according to claim 19, wherein In step (1), the aqueous lactic acid solution has a concentration of 60 - 100 wt%; The lactic acid is L-lactic acid and / or D-lactic acid, and the optical purity > 99.5%; In step (1), the mass ratio of the catalyst to the aqueous lactic acid solution is 1:100 - 5000; In step (1), for the temperature increase, the rate is 0.5 - 2 °C / min; In steps (1) and (2), the stirring speed is 50 - 400 r / min.

22. The method according to claim 21, wherein The aqueous lactic acid solution has a concentration of 90 - 95 wt%.

23. The method according to claim 21, wherein The mass ratio of the catalyst to the aqueous lactic acid solution is 1:500 - 1:2000.

24. The method according to claim 21, wherein For the temperature increase, the rate is 1 °C / min.

25. The method according to claim 21, wherein For the stirring, the speed is 150 - 250 r / min.

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