CN115710284A - Catalyst for synthesizing lactide from lactic acid and preparation method and application thereof - Google Patents

Abstract

The invention provides a catalyst for synthesizing lactide by lactic acid and a preparation method and application thereof, wherein the catalyst has a structure shown as a formula (1), and has the characteristics of simple structure, easily obtained raw materials, simple and convenient synthesis, adjustable structure and the like. The central metal is nontoxic and pollution-free elements such as calcium, magnesium, zinc and the like; 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 the lactic acid; the lactide used for catalyzing the prepolymerization and the depolymerization of the lactic acid has high light purity and low free lactic acid content.

Description

Catalyst for synthesizing lactide from lactic acid and preparation method and application thereof

Technical Field

The invention relates to a catalyst, a preparation method thereof and application of the catalyst in a lactide synthesis process by lactic acid.

Background

At present, the human society faces the problems of serious white pollution and limited petroleum resources, and the vigorous development of renewable and degradable plastics is urgent. The polylactic acid serving as the hot biodegradable plastic has the advantages of excellent mechanical property, chemical stability, biocompatibility and the like. The lactic acid serving as a raw material is derived from renewable resources such as corn and the like, only water and carbon dioxide are generated after complete degradation, and the plastic is environment-friendly.

Two common synthetic methods of polylactic acid are available, one is polylactic acid formed by direct dehydration condensation of lactic acid, but water generated in a reaction system is difficult to remove, and the molecular weight of the generated polylactic acid is not high. The other method is to dehydrate and cyclize lactic acid to form cyclic dimer lactide, and then catalyze the lactide to carry out ring-opening polymerization to obtain the high molecular weight polylactic acid. Wherein, the higher the chemical purity and the optical purity of the lactide are, the better the performance and the wider the application of the polylactic acid obtained by catalytic polymerization are.

At present, lactic acid is used as a raw material for industrial lactide synthesis, and a metal salt catalyst (such as stannous octoate, stannous chloride and the like, see US5053522 for details) is adopted. The metallic tin has certain biological toxicity and is easy to pollute products, and the catalyst is difficult to regenerate after being inactivated. Zinc oxide (CN 1616450) in the zinc catalyst has better catalytic performance, but the zinc oxide is a heterogeneous catalyst, is difficult to be uniformly mixed with a lactic acid system, is easy to deposit at the bottom of a reactor, blocks a pipeline, and is not beneficial to industrialization. It can be found from the published literature (CN 101903370) that the content of free lactic acid in crude lactide synthesized industrially at present is still relatively high, substantially 1.8% or more, and free lactic acid and lactic acid dimer directly affect downstream polymerization applications and require further purification treatment. If the content of lactic acid and lactic acid dimer in crude lactide can be reduced, the synthesis steps can be reduced, the energy consumption can be reduced, and the synthesis process can be optimized.

Disclosure of Invention

Aiming at the problems in the prior art, the invention provides a catalyst for synthesizing lactide by lactic acid and a preparation method thereof, wherein the catalyst is an organic metal complex, contains aminopyridine and alkoxy structure, and has the characteristics of simple structure, easily obtained raw materials, simple and convenient synthesis, adjustable structure and the like. The space environment and the electronic effect of the metal center can be optimized by adjusting the ligand substituent, so that the catalytic activity of the catalyst is improved. The alkoxy structure connected with the metal active center not only has the function of stabilizing the metal active center, but also can be used as a polymerization initiation group to shorten the prepolymerization reaction time of the lactic acid. In addition, the catalysts of the invention also have very good hydrolysis resistance compared to the existing complexes of this class.

The invention also provides a process method for preparing lactide by using the catalyst to perform polycondensation of lactic acid into polylactic acid and then performing catalytic depolymerization. The catalyst provided by the invention adopts nontoxic pollution-free biocompatible metals such as calcium, magnesium and zinc as a catalytic center, and can realize high-activity catalysis of lactic acid prepolymerization and depolymerization to generate lactide by matching with a ligand structure with an adjustable structure, and the prepared lactide has high optical purity and low free lactic acid content.

The invention provides a catalyst for synthesizing lactide by lactic acid, which has a structure shown as a formula (1):

in the formula, R ₁ Represents hydrogen, alkyl with a C1-C20 straight chain, branched chain or cyclic structure, mono-or poly-aryl substituted alkyl with C7-C30, halogen; preferably C1-C10 linear chain, branched chain or cyclic structure alkyl, C7-C18 mono-or poly-aryl substituted alkyl, halogen; more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, phenyl, benzyl, chlorine, bromine, iodine, etc.; more preferably methyl, ethyl, isopropyl, cyclohexyl;

R ₂ represents C1-C10 linear chain, branched chain or cyclic structure alkyl, C7-C30 mono-or poly-aryl substituted alkyl; preferably C1-C8 linear chain, branched chain or cyclic structure alkyl, C7-C18 mono-or poly-aryl substituted alkyl; more preferably methyl, ethyl, n-butylPropyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl and the like; more preferably methyl, ethyl, isopropyl, cyclohexyl;

m is Mg, ca or Zn, preferably Zn.

Preferably, the catalyst for synthesizing lactide by lactic acid is any one of complexes shown in the following structural formulas [1] to [16]:

the invention also provides a preparation method of the catalyst for synthesizing lactide by lactic acid, which comprises the following steps:

1) Mixing amino-substituted aryl bromide, metal magnesium and a solvent A for reaction to prepare amino-substituted aryl magnesium bromide;

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

3) Mixing the aminopyridine ligand obtained in the step 2), a hexamethyldisilazane-based amino metal complex and a solvent C for coordination reaction, and then adding an alcohol compound for alkoxylation reaction to obtain the catalyst for synthesizing lactide from lactic acid.

In step 1) of the present invention, the amino-substituted aryl bromide is any one selected from compounds having a structure represented by formula (2):

in the formula, R ₁ Definition of R in the formula (1) ₁ Are identical, i.e. R ₁ Represents hydrogen, alkyl with a C1-C20 straight chain, branched chain or cyclic structure, mono-or poly-aryl substituted alkyl with C7-C30, halogen; preferably C1-C10 linear, branched or cyclic alkyl, C7-C18 mono-or polyaryl-substituted alkyl, halogen; more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexylCyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, phenyl, benzyl, chloro, bromo, iodo, etc.; more preferably methyl, ethyl, isopropyl, cyclohexyl;

in step 1) of the present invention, the molar ratio of the amino-substituted aryl bromide to the metal magnesium is 1:1-2, preferably 1:1.2-1.3.

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

the amount of solvent A is 1-15mL per millimole of amino-substituted aryl bromide.

In the step 1) of the invention, the amino-substituted aryl bromide is continuously added, preferably dropwise added, and the adding time is 30-60min, preferably 30min.

In the step 1), the reaction is carried out at the temperature of 30-60 ℃, preferably 45-55 ℃ for 2-5h, preferably 2-3h;

preferably, the reaction is completed and then a separation process is included, which is a routine operation in the field and has no special requirement, for example, after the reaction is completed, the reaction product is cooled to room temperature, kept stand for liquid separation, and the supernatant liquid is taken to remove the solvent, so that the amino-substituted aryl magnesium bromide is obtained.

In step 2) of the invention, the molar ratio of the amino-substituted aryl magnesium bromide to the 2-bromopyridine is 1:1-1.5, preferably 1:1-1.2.

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

The catalyst is used in an amount of 1 to 5, preferably 2 to 3, mole percent based on the amino-substituted aryl magnesium bromide.

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

the amount of solvent B is 1-15mL per millimole of amino-substituted aryl magnesium bromide.

In step 2) of the invention, the coupling reaction is carried out at a temperature of 0-20 ℃, preferably 0-5 ℃ for 6-12h, preferably 6-8h.

In the step 2), the reaction also comprises the processes of adding water for quenching and post-treatment after the reaction is finished;

adding water for quenching, wherein the adding amount of the water is 1-2 times of the mass of the reaction system;

the work-up is a routine operation in the art and is not particularly critical, for example, in some cases the preferred method is to extract the quenched reaction solution with ethyl acetate and the organic phase with Na ₂ SO ₄ Drying, filtering and concentrating under reduced pressure, purifying by n-pentane/ethyl acetate column, and vacuum drying to remove solvent.

In step 3), the general formula of the hexamethyldisilazane-based amino metal complex is M [ N (SiMe) ₃ ) ₂ ] ₂ Wherein M represents a metal element, is defined as in formula (1), i.e., selected from Mg, ca or Zn, preferably Zn, and Me represents a methyl group.

The molar ratio of the hexamethyldisilazane-based amino metal complex to the aminopyridine ligand is 1-1.5:1, preferably 1:1.

in step 3), the solvent C is at least one selected from tetrahydrofuran and toluene, preferably tetrahydrofuran;

the amount of solvent C is 5-20mL per mmol of aminopyridine ligand.

In step 3), the alcohol compound has a general formula of R ₂ OH, wherein R ₂ Definition and R in formula (1) ₂ Are identical, i.e. R ₂ Represents C1-C10 linear chain, branched chain or cyclic structure alkyl, C7-C30 mono-or poly-aryl substituted alkyl; preferably C1-C8 linear chain, branched chain or cyclic structure alkyl, C7-C18 mono-or poly-aryl substituted alkyl; more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, etc.; more preferably methyl, ethyl, isopropyl, cyclohexyl;

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

in the step 3), the coordination reaction is carried out at the temperature of 10-50 ℃, preferably 20-30 ℃ for 6-12h, preferably 6-8h;

the alkoxylation reaction is carried out at the temperature of 10-50 ℃, preferably 20-30 ℃ for 4-8h, preferably 4h;

in step 3) of the present invention, the alkoxylation reaction further comprises a post-treatment process, wherein the post-treatment process is a conventional operation in the art and has no special requirement, for example, filtration, solvent removal under reduced pressure, recrystallization and the like can be adopted, wherein the recrystallization solvent preferably adopts a solvent with a volume ratio of 1:5 of tetrahydrofuran and n-hexane.

In the preparation method of the invention, correspondingly, the amino-substituted aryl magnesium bromide generated in the step 1) and the aminopyridine ligand generated in the step 2) are compounds with structures shown in formulas (3) and (4):

r in the formula (3) and the formula (4) ₁ And R in formula (2) ₁ The same is true.

The invention also provides a method for synthesizing lactide by lactic acid, which takes the lactic acid aqueous solution as the raw material, and carries out dehydration polycondensation reaction to generate lactic acid oligomer and high-temperature depolymerization reaction to generate lactide under the catalytic action of the catalyst.

Preferably, the method for synthesizing lactide from lactic acid of the present invention comprises the steps of:

(1) Mixing lactic acid aqueous solution with a catalyst, stirring and reacting for 1-8h, preferably 2-4h, at the absolute pressure of 1-10kPa, preferably 2-5kPa, and the temperature of 20-50 ℃, preferably 20-30 ℃, and then heating to 120-180 ℃, preferably 150-180 ℃, stirring and reacting for 3-10h, preferably 3-4h, so that lactic acid is dehydrated and polycondensed to generate lactic acid oligomer with the molecular weight of 500-2000 Da;

(2) The reaction system of the step (1) is stirred and reacted for 1-4h, preferably 1-1 h, under the absolute pressure of 1-4kPa, preferably 1-2kPa, and at the temperature of 180-250 ℃, preferably 200-230 ℃, so that the lactic acid oligomer is depolymerized at high temperature to prepare the lactide.

In step (1) of the present invention, the concentration of the aqueous solution of lactic acid is 60 to 100wt%, preferably 90 to 95wt%;

the lactic acid is L-lactic acid and/or D-lactic acid, and the optical purity is more than 99.5%.

In step (1) of the present invention, the mass ratio of the catalyst to the aqueous lactic acid solution is 1.

In the step (1) of the invention, the temperature is raised at a rate of 0.5-2 ℃/min, preferably 1 ℃/min.

In the steps (1) and (2) of the invention, the stirring is carried out at a rotating speed of 50-400r/min, preferably 150-250r/min.

The optical purity of the lactide prepared by the method is not less than 96 percent and can reach more than 98 percent, and the content of free lactic acid is less than 0.90 weight percent, preferably as low as 0.21 weight percent.

Compared with the prior art, the technical scheme of the invention has the beneficial effects that:

the invention designs a novel catalyst for synthesizing lactide by lactic acid, in particular to an aminopyridine coordinated alkoxy metal complex. The catalyst of the invention adopts nontoxic, pollution-free and biocompatible metals such as calcium, magnesium, zinc and the like, and has high catalytic activity for catalyzing lactic acid polymerization and lactic acid oligomer depolymerization. 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 ions obtain two shared electrons, and meanwhile, the nitrogen atom on the pyridine structure is coordinated with the metal center, and the shared electrons enable the metal center to be more stable, so that the catalyst shows good stability and solubility.

The metal active center of the catalyst is connected with an alkoxy structure, and can be quickly replaced by hydroxyl of lactic acid during catalytic reaction, so that the time required by initiating reaction is greatly reduced, and the catalytic performance of the catalyst is improved. Meanwhile, the alkoxy is an electron-donating group, so that a stable structure can be formed in the electron-deficient metal, and the stability and hydrolysis resistance of the catalyst are further improved.

Detailed Description

The present invention will be described in detail below with reference to specific examples. The scope of the invention is not limited to the specific embodiments.

The sources of the raw materials in the examples of the present invention and comparative examples are shown in the following tables, and other raw materials of the reagents are general commercial products unless otherwise specified.

The test methods used in the examples of the invention and the comparative examples are as follows:

hydrolysis resistance: adding 0.1mL of pure water into the tested nuclear magnetic tube, uniformly mixing, testing again, if the nuclear magnetic result is consistent with that before, proving that the complex is not hydrolyzed, and if the nuclear magnetic result is changed, proving that a new substance is generated and the complex is hydrolyzed; the test was performed every 24h and the total time at which hydrolysis occurred was recorded.

Stability: and (3) placing the tested nuclear magnetic tube in an open manner, testing once every 24h, comparing nuclear magnetic results, if the nuclear magnetic results are consistent with the nuclear magnetic results, proving that the complex is not changed, if the nuclear magnetic results are changed, proving that the complex structure is changed, and recording the total time of the nuclear magnetic results.

Optical purity: weighing a lactide sample on an analytical balance, dissolving the lactide sample by using chromatographic pure acetonitrile, and analyzing and detecting the content of the L-lactide by using gas chromatography to obtain the optical purity of the sample.

Content of free lactic acid: weighing a sample on an analytical balance, dissolving the sample by using chromatographic pure acetonitrile, adding HMDS and pyridine for derivatization, and analyzing and detecting the content of the lactic acid by using gas chromatography.

And (3) testing molecular weight: the samples were weighed on an analytical balance, dissolved in chromatographically pure tetrahydrofuran, filtered through a 0.45 μm organic filter and analyzed by gel permeation chromatography for molecular weight determination.

Gas chromatography: using DB-5 capillary column and hydrogen flame ionization detector, and performing qualitative and quantitative analysis on effective components by external standard method under the conditions of carrier gas flow rate of 1.5mL/min, split ratio of 30, injection port temperature of 180 ℃, column temperature of 250 ℃ and detector chamber temperature of 180 ℃.

Gel permeation chromatography: PS is taken as a standard substance, XT450, XT125 and XT45 three columns are connected in series, chromatographic pure dichloromethane is taken as a mobile phase, the flow rate is 1mL/min, the column temperature is 60 ℃, and the determination is carried out at the temperature of 60 ℃ in a flow cell.

Example 1

1) Synthesizing 2- (N-methylaniline) magnesium bromide shown as the following formula:

to a dry schlenk bottle, a stirrer and active magnesium powder (0.316g, 13mmol) were added, and replaced three times with nitrogen. Then 10mL of an anhydrous THF solution of 1mmol/mL of 2-bromo-N-methylaniline was added dropwise over 30min, followed by reaction at 50 ℃ for 2h. And after the reaction is finished, cooling to room temperature, standing for liquid separation, taking supernatant liquor, and removing the solvent to obtain the 2- (N-methylaniline) magnesium bromide.

2) Synthesizing a methyl-substituted aminopyridine ligand a of the formula:

2-bromopyridine (1.58g, 10 mmol), niCl ₂ (dppp) ₂ (108.41g, 0.2mmol) and 10mL of anhydrous THF were combined, then 10mmol of the 2- (N-methylaniline) magnesium bromide prepared in step 1) was added, followed by reaction at 0 ℃ for 8h. The reaction mixture was quenched by addition of 20mL of water and extracted with ethyl acetate, and the combined organic phases were Na ₂ SO ₄ Drying, filtering and concentrating under reduced pressure, purifying with n-pentane/ethyl acetate column, and vacuum drying to obtain methyl substituted aminopyridine ligand A (1.676 g, 91% yield).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.25(dd,1H),δ8.37(dd,1H),δ7.40(dd,1H),δ7.38(dd,1H),δ7.14(dd,1H),δ7.03(dd,1H),δ6.90(dd,1H),δ6.85(dd,1H),δ6.82(m,1H),δ3.01(s,3H).

Example 2

1) Synthesis of 2- (N-ethylaniline) magnesium bromide of the formula:

a dry schlenk flask was charged with a stir bar and active magnesium powder (0.379g, 15.6 mmol) and replaced with nitrogen three times. Then 10mL of a 1mmol/mL solution of 2-bromo-N-ethylaniline in anhydrous THF was added dropwise over 30min, followed by reaction at 45 ℃ for 2.5h. And after the reaction is finished, cooling to room temperature, standing for liquid separation, taking supernatant liquor, and removing the solvent to obtain the 2- (N-ethylaniline) magnesium bromide.

2) Synthesizing an ethyl-substituted aminopyridine ligand B of the formula:

2-bromopyridine (1.74g, 11mmol), niCl ₂ (dppp) ₂ (108.41g, 0.2mmol) and 12mL of anhydrous THF were mixed, and 10mmol of 2- (N-ethylaniline) magnesium bromide prepared in step 1) was added, followed by reaction at 2 ℃ for 6 hours. The reaction mixture was quenched by addition of 20mL water and extracted with ethyl acetate, and the combined organic phases were Na ₂ SO ₄ Drying, filtering and concentrating under reduced pressure, purifying with n-pentane/ethyl acetate column, and vacuum drying to obtain ethyl substituted aminopyridine ligand B (1.765 g, 89% yield).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.28(dd,1H),δ8.39(dd,1H),δ7.42(dd,1H),δ7.40(dd,1H),δ7.16(dd,1H),δ7.08(dd,1H),δ6.90(dd,1H),δ6.88(dd,1H),δ6.80(m,1H),δ3.45(q,2H),δ1.28(t,3H).

Example 3

1) Synthesis of 2- (N-cyclohexylaniline) magnesium bromide represented by the following formula:

to a dry schlenk bottle, a stirrer and active magnesium powder (0.316g, 13mmol) were added, and replaced three times with nitrogen. Then 11mL of a 1mmol/mL solution of 2-bromo-N-cyclohexylaniline in anhydrous THF was added dropwise over 30min, followed by reaction at 52 ℃ for 2h. And after the reaction is finished, cooling to room temperature, standing for liquid separation, taking supernatant liquor, and removing the solvent to obtain the 2- (N-cyclohexylaniline) magnesium bromide.

2) Synthesizing a cyclohexyl substituted aminopyridine ligand C shown in the following formula:

2-bromopyridine (2.05g, 13mmol), niCl ₂ (dppp) ₂ (108.41g, 0.2mmol) and 13mL of anhydrous THF were mixed, then 10mmol of the 2- (N-cyclohexylaniline) magnesium bromide prepared in step 1) was added, followed by reaction at 0 ℃ for 6h. The reaction mixture was quenched by addition of 20mL of water and extracted with ethyl acetate, and the combined organic phases were Na ₂ SO ₄ Drying, filtering and concentrating under reduced pressure, purifying with n-pentane/ethyl acetate column, and vacuum drying to obtain cyclohexyl substituted aminopyridine ligand C (2.221 g, yield 88%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.32(dd,1H),δ8.40(dd,1H),δ7.38(dd,1H),δ7.36(dd,1H),δ7.20(dd,1H),δ7.01(dd,1H),δ6.90(dd,1H),δ6.86(dd,1H),δ4.55(s,1H),δ2.57(m,1H),δ1.71(m,4H),δ1.46(m,2H),δ1.21(m,4H).

Example 4

Synthesizing a methyl-substituted methoxy zinc complex [1]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.425g, 1.1mmol) and 11mL of anhydrous THF were mixed with stirring, and the methyl-substituted aminopyridine ligand A (0.184g, 1mmol) prepared in example 1 was added thereto, reacted at 28 ℃ for 7 hours, and then anhydrous methanol (0.048g, 1.5mmol) was added to the reaction mixture, and the reaction was further stirred at 25 ℃ for 5 hours. Filtering to remove substances, removing the solvent by decompression, and separating by using a solvent with a volume ratio of 1: recrystallizing the tetrahydrofuran/normal hexane mixed solution to obtainThe desired product (0.185 g,66% yield).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.33(dd,1H),δ8.43(dd,1H),δ7.46(dd,1H),δ7.44(dd,1H),δ7.20(dd,1H),δ7.09(dd,1H),δ6.96(dd,1H),δ6.91(dd,1H),δ3.01(s,3H),δ2.78(s,3H).

The complex [1] is tested for hydrolysis resistance, and nuclear magnetic results are unchanged after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 5

Synthesizing methyl-substituted ethoxy zinc complex [2]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.502g, 1.3 mmol) and 15mL of anhydrous THF were mixed well with stirring, and the methyl-substituted aminopyridine ligand A (0.184g, 1mmol) prepared in example 1 was added thereto, and reacted at 20 ℃ for 11 hours, and then absolute ethanol (0.055g, 1.2mmol) was added to the reaction mixture, and the reaction was continued at 30 ℃ for 4 hours with stirring. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5 to obtain the target product (0.185 g, yield 63%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.30(dd,1H),δ8.42(dd,1H),δ7.45(dd,1H),δ7.43(dd,1H),δ7.19(dd,1H),δ7.08(dd,1H),δ6.95(dd,1H),δ6.90(dd,1H),δ3.57(q,2H),δ2.78(s,3H),δ1.10(t,3H).

The hydrolysis resistance of the complex [2] is tested, and the nuclear magnetism result is not changed after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in an open way for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 6

Synthesizing a methyl-substituted zinc isopropoxide complex [3]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.540g, 1.4mmol) and 15mL of anhydrous THF were mixed by stirring and mixed, and the methyl-substituted aminopyridine ligand A (0.184g, 1mmol) prepared in example 1 was further added thereto, and reacted at 22 ℃ for 10 hours, and then anhydrous isopropanol (0.066 g, 1.1mmol) was added to the reaction mixture, and the reaction was further stirred at 25 ℃ for 5 hours. Filtering to remove substances, removing the solvent by decompression, and separating by using a solvent with a volume ratio of 1:5 to obtain the target product (0.177 g, yield 58%).

¹ H NMR(400MHz,CDCl ₃ ,298K)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(q,1H),δ2.78(s,3H),δ1.13(t,6H).

The hydrolysis resistance of the complex [3] is tested, and the nuclear magnetism result is not changed after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 7

Synthesizing methyl-substituted n-butoxy zinc complex [4]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.579g, 1.5mmol) and 16mL of anhydrous THF were mixed well with stirring, then methyl-substituted aminopyridine ligand A (0.184g, 1mmol) prepared in example 1 was added, and reaction was carried out at 30 ℃ for 10h, then anhydrous n-butanol (0.089g, 1.2mmol) was added to the reaction mixture, and reaction was continued at 25 ℃ for 6h with stirring. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5 to obtain the target product (0.196 g, yield 61%).

¹ H NMR(400MHz,CDCl ₃ ,298K)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),δ3.53(q,2H),δ2.78(s,3H),δ1.53(dd,2H),δ1.45(dd,2H),δ0.90(t,3H).

The complex [4] is tested for hydrolysis resistance, and nuclear magnetic results are unchanged after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in an open way for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 8

Synthesis of Ethyl-substituted Phenoxyzinc Complex [5]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.386 g, 1mmol) and 10mL of anhydrous THF were mixed with stirring, and the ethyl-substituted aminopyridine ligand B (0.198g, 1mmol) prepared in example 2 was added thereto, and reacted at 20 ℃ for 12 hours, and then anhydrous phenol (0.122g, 1.3mmol) was added to the reaction mixture, and the reaction was further stirred at 20 ℃ for 5 hours. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5 to obtain the target product (0.196 g, yield 55%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.33(dd,1H),δ8.42(dd,1H),δ7.45(dd,1H),δ7.44(dd,1H),δ7.25(dd,2H),δ7.21(dd,1H),δ7.09(dd,1H),δ6.93(dd,1H),δ6.91(dd,2H),δ6.90(dd,1H),δ6.88(d,1H),δ3.10(q,2H),δ1.14(t,3H).

The complex [5] is tested for hydrolysis resistance, and nuclear magnetic results are unchanged after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 9

Synthesis of Ethyl-substituted Cyclohexyloxy Zinc Complex [6]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.463g, 1.2mmol) and 8mL of anhydrous THF were mixed with stirring, and ethyl-substituted aminopyridine ligand B (0.198g, 1mmol) prepared in example 2 was added thereto, and reacted at 20 ℃ for 11 hours, and anhydrous cyclohexanol (0.100g, 1.5 mmol) was added to the reaction mixture, and the reaction was continued with stirring at 25 ℃ for 6 hours. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5, the resulting mixture was recrystallized from a tetrahydrofuran/n-hexane mixture to obtain the desired product (0.213 g, yield 59%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.32(dd,1H),δ8.42(dd,1H),δ7.44(dd,1H),δ7.42(dd,1H),δ7.20(dd,1H),δ7.09(dd,1H),δ6.92(dd,1H),δ6.88(dd,1H),δ3.54(m,1H),δ3.10(t,2H),δ1.72(m,2H),δ1.57(m,4H),δ1.47(m,2H),δ1.44(m,2H),δ1.14(t,3H).

The complex [6] is tested for hydrolysis resistance, and nuclear magnetic results are unchanged after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 10

Synthesis of cyclohexyl-substituted ethoxyzinc Complex [7]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.502g, 1.3 mmol) and 12mL of anhydrous THF were mixed well with stirring, and then cyclohexyl-substituted aminopyridine ligand C (0.252g, 1 mmol) prepared in example 3 was added thereto, and reacted at 28 ℃ for 8 hours, and then absolute ethanol (0.045g, 1.4 mmol) was added to the reaction mixture, and the reaction was continued with stirring at 27 ℃ for 4 hours. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5 tetrahydrofuran/n-butylThe hexane mixture was recrystallized to obtain the objective product (0.195 g, yield 54%).

¹ H NMR(400MHz,CDCl ₃ ,298K)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).

The hydrolysis resistance of the complex [7] is tested, and the nuclear magnetic result is not changed after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in an open way for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 11

Synthesizing cyclohexyl substituted zinc isopropoxide complex [8]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.386g, 1mmol) and 5mL of anhydrous THF were mixed and stirred uniformly, and then cyclohexyl-substituted aminopyridine ligand C (0.252g, 1mmol) prepared in example 3 was added thereto, and reacted at 25 ℃ for 10 hours, and then anhydrous isopropanol (0.072g, 1.2mmol) was added to the reaction solution, and the reaction was stirred at 26 ℃ for 4 hours. Filtering to remove substances, removing the solvent by decompression, and separating by using a solvent with a volume ratio of 1:5, recrystallizing the tetrahydrofuran/n-hexane mixed solution to obtain the target product (0.229 g, yield 61%).

¹ H NMR(400MHz,CDCl ₃ ,298K)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(m,1H),δ2.57(m,1H),δ1.71(m,4H),δ1.47(m,2H),δ1.11(m,4H),δ1.13(t,6H).

The hydrolysis resistance of the complex [8] is tested, and the nuclear magnetic result is not changed after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in an open way for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 12

Synthesizing a methyl-substituted methoxy magnesium complex [9]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and Mg [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.380g, 1.1mmol) and 10mL of anhydrous THF were mixed with stirring, and methyl-substituted aminopyridine ligand A (0.184g, 1mmol) prepared in example 1 was added thereto, and reacted at 25 ℃ for 9 hours, and anhydrous methanol (0.048g, 1.5mmol) was added to the reaction mixture, followed by stirring at 30 ℃ for additional 4 hours. Filtering to remove substances, removing the solvent by decompression, and separating by using a solvent with a volume ratio of 1:5 to obtain the target product (0.146 g, yield 61%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.30(dd,1H),δ8.40(dd,1H),δ7.43(dd,1H),δ7.40(dd,1H),δ7.17(dd,1H),δ7.06(dd,1H),δ6.93(dd,1H),δ6.88(dd,1H),δ3.28(s,3H),δ2.75(s,3H).

The hydrolysis resistance of the complex [9] is tested, and the nuclear magnetic result is not changed after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 13

Synthesis of methyl-substituted ethoxymagnesium Complex [10]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and Mg [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.345g, 1mmol) and 13mL of anhydrous THF were mixed with stirring, and the methyl-substituted aminopyridine ligand A (0.184g, 1mmol) prepared in example 1 was added thereto, and reacted at 30 ℃ for 8 hours, and then anhydrous ethanol (0.069g, 1.5mmol) was added to the reaction mixture, and the reaction was further stirred at 25 ℃ for 6 hours. Filtering to remove the solvent, removing the solvent under reduced pressure, and measuring the volumeThe ratio is 1:5 to obtain the target product (0.119 g, yield 47%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.35(dd,1H),δ8.48(dd,1H),δ7.40(dd,1H),δ7.38(dd,1H),δ7.10(dd,1H),δ7.01(dd,1H),δ6.90(dd,1H),δ6.88(dd,1H),δ3.54(q,2H),δ2.76(s,3H),δ1.12(t,3H).

The hydrolysis resistance of the complex [10] is tested, and the nuclear magnetism result is not changed after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 14

Synthesis of methyl-substituted magnesium isopropoxide Complex [11]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and Mg [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.518g, 1.5mmol) and 10mL of anhydrous THF were mixed with stirring, and the methyl-substituted aminopyridine ligand A (0.184g, 1mmol) prepared in example 1 was added thereto, and reacted at 25 ℃ for 12 hours, and then anhydrous isopropanol (0.078g, 1.3mmol) was added to the reaction mixture, and the reaction was further stirred at 30 ℃ for 5 hours. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5, recrystallizing the tetrahydrofuran/n-hexane mixed solution to obtain the target product (0.136 g, yield 51%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.37(dd,1H),δ8.51(dd,1H),δ7.95(dd,1H),δ7.50(dd,1H),δ7.25(dd,1H),δ7.00(dd,1H),δ6.86(dd,1H),δ6.69(dd,1H),δ3.57(q,1H),δ2.72(s,3H),δ1.13(t,6H).

The hydrolysis resistance of the complex [11] is tested, and the nuclear magnetic result is not changed after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 15

Synthesis of methyl-substituted n-butoxy magnesium Complex [12]

A dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and Mg [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.345g, 1mmol) and 11mL of anhydrous THF were mixed with stirring, and the methyl-substituted aminopyridine ligand A (0.184g, 1mmol) prepared in example 1 was added thereto, and reacted at 30 ℃ for 8 hours, and anhydrous n-butanol (0.089g, 1.2mmol) was added to the reaction mixture, and the reaction was further stirred at 28 ℃ for 4 hours. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5 to obtain the target product (0.185 g,66% yield).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.37(dd,1H),δ8.52(dd,1H),δ7.94(dd,1H),δ7.49(dd,1H),δ7.25(dd,1H),δ7.00(dd,1H),δ6.86(dd,1H),δ6.67(dd,1H),δ3.50(q,2H),δ2.77(s,3H),δ1.53(dd,2H),δ1.44(dd,2H),δ0.91(t,3H).

The hydrolysis resistance of the complex [12] is tested, and the nuclear magnetic result is not changed after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 16

Synthesis of Ethyl-substituted Phenoxymagnesium Complex [13]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and Mg [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.414g, 1.2mmol) and 10mL of anhydrous THF were mixed with stirring, and ethyl-substituted aminopyridine ligand B (0.198g, 1mmol) prepared in example 2 was added thereto, and reacted at 25 ℃ for 10 hours, and then anhydrous phenol (0.132g, 1.4 mmol) was added to the reaction mixture, and the reaction was continued at 30 ℃ for 4 hours with stirring. Filtering to remove impurities, removing solvent under reduced pressure, and mixingIs 1:5, recrystallizing the tetrahydrofuran/n-hexane mixed solution to obtain the target product (0.160 g, yield 51%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.36(dd,1H),δ8.47(dd,1H),δ7.42(dd,1H),δ7.40(dd,1H),δ7.30(dd,2H),δ7.20(dd,1H),δ7.11(dd,1H),δ6.90(dd,1H),δ6.88(dd,2H),δ6.85(dd,1H),δ6.83(d,1H),δ3.13(q,2H),δ1.15(t,3H).

The hydrolysis resistance of the complex [13] is tested, and the nuclear magnetic result is not changed after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 17

Synthesis of Ethyl-substituted cyclohexyloxymagnesium Complex [14]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and Mg [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.414g, 1.2mmol) and 12mL of anhydrous THF were mixed with stirring, and ethyl-substituted aminopyridine ligand B (0.198g, 1mmol) prepared in example 2 was added thereto, and reacted at 28 ℃ for 8 hours, and anhydrous cyclohexanol (0.150g, 1.5 mmol) was added thereto, and the reaction was further stirred at 26 ℃ for 4 hours. Filtering to remove substances, removing the solvent by decompression, and separating by using a solvent with a volume ratio of 1:5, recrystallizing the tetrahydrofuran/normal hexane mixed solution to obtain a target product (0.212g, 66%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.35(dd,1H),δ8.45(dd,1H),δ7.45(dd,1H),δ7.40(dd,1H),δ7.25(dd,1H),δ7.04(dd,1H),δ6.90(dd,1H),δ6.87(dd,1H),δ3.50(m,1H),δ3.12(t,2H),δ1.75(m,2H),δ1.60(m,4H),δ1.48(m,2H),δ1.45(m,2H),δ1.13(t,3H).

The hydrolysis resistance of the complex [14] is tested, and the nuclear magnetic result is not changed after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in an open way for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 18

Synthesis of cyclohexyl-substituted ethoxymagnesium Complex [15]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and Mg [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.345g, 1mmol) and 10mL of anhydrous THF were mixed well with stirring, and then cyclohexyl-substituted aminopyridine ligand C (0.252g, 1mmol) prepared in example 3 was added thereto, and reacted at 25 ℃ for 8 hours, and then absolute ethanol (0.060g, 1.3mmol) was added to the reaction mixture, and the reaction was continued with stirring at 25 ℃ for 6 hours. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5 to obtain the target product (0.189 g, yield 59%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.37(dd,1H),δ8.55(dd,1H),δ7.95(dd,1H),δ7.53(dd,1H),δ7.25(dd,1H),δ7.02(dd,1H),δ6.84(dd,1H),δ6.70(dd,1H),δ3.57(dd,2H),δ2.55(m,1H),δ1.73(m,4H),δ1.44(m,2H),δ1.11(m,4H),δ1.10(t,3H).

The complex [15] is tested for hydrolysis resistance, and nuclear magnetic results are unchanged after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 19

Synthesis of cyclohexyl-substituted magnesium isopropoxide Complex [16]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and Mg [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.345g, 1mmol) and 10mL of anhydrous THF were stirred and mixed well, and the cyclohexyl-substituted aminopyridine ligand C (0.252g, 1mmol) prepared in example 3 was added thereto, reacted at 25 ℃ for 8 hours, and anhydrous isopropanol (0.0)90g,1.5 mmol) and stirring the mixture at 25 ℃ for 4 hours. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5, the resulting mixture was recrystallized from a tetrahydrofuran/n-hexane mixture to obtain the desired product (0.211 g, yield 63%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.37(dd,1H),δ8.51(dd,1H),δ7.94(dd,1H),δ7.50(dd,1H),δ7.25(dd,1H),δ7.08(dd,1H),δ6.80(dd,1H),δ6.69(dd,1H),δ3.54(m,1H),δ2.57(m,1H),δ1.73(m,4H),δ1.47(m,2H),δ1.13(m,4H),δ1.10(t,6H).

The complex [16] is tested for hydrolysis resistance, and nuclear magnetic results are unchanged after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in an open way for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

Example 20

Synthesis of lactide from lactic acid:

(1) 1000g of an aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) was charged into a three-necked flask, and then 1g of the methyl-substituted methoxy zinc complex prepared in example 9 was added thereto, and the mixture was stirred and reacted at 25 ℃ under a nitrogen atmosphere of 4kPaA for 2 hours, and then heated to 120 ℃ at a rate of 2 ℃/min for 3 hours under stirring to obtain a lactic acid oligomer having a molecular weight of 835 Da.

(2) The absolute pressure of the reaction system in the step (1) is kept at 4kPa, the temperature is raised to 230 ℃, the reaction is carried out for 1h, and then distillation is carried out, thus obtaining 536.3g of white crystalline L-lactide with yield of 71%, optical purity of 96.1% and free lactic acid content of 0.51wt%.

Example 21

Synthesis of lactide from lactic acid:

(1) 1000g of an aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) was charged into a three-necked flask, and then 1g of the methyl-substituted methoxy zinc complex prepared in example 10 was added thereto, and the mixture was stirred and reacted at 25 ℃ under a nitrogen atmosphere of 4kPaA for 2 hours, and then heated to 120 ℃ at a rate of 2 ℃/min for 3 hours with stirring to obtain a lactic acid oligomer having a molecular weight of 805 Da.

(2) The absolute pressure of the reaction system in the step (1) is kept at 4kPa, the temperature is raised to 220 ℃, the reaction is carried out for 1h, and then the distillation is carried out, thus obtaining 533.2g of white crystalline L-lactide with the yield of 71%, the optical purity of 96.6% and the content of free lactic acid of 0.53wt%.

Example 22

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) is added into a three-neck flask, 1g of [2] methyl-substituted zinc ethoxide complex is added, stirring reaction is carried out for 2h at 25 ℃ under the nitrogen atmosphere of 4000PaA, then the temperature is increased to 150 ℃ at the speed of 2 ℃/min, stirring reaction is carried out for 3h, and lactic acid oligomer with the molecular weight of 1221Da is obtained.

(2) The absolute pressure of the reaction system in the step (1) is kept at 4000Pa, the temperature is raised to 230 ℃, the reaction is carried out for 1h, and then the distillation is carried out, thus obtaining 548.2g of white crystalline L-lactide with the yield of 73 percent, the optical purity of 96.5 percent and the content of free lactic acid of 0.34 weight percent.

Example 23

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) is added into a three-neck flask, 1g of [3] methyl-substituted zinc isopropoxide complex is added, stirring reaction is carried out for 2h at 25 ℃ under the nitrogen atmosphere of 4000PaA, then the temperature is increased to 180 ℃ at the speed of 2 ℃/min, stirring reaction is carried out for 3h, and lactic acid oligomer with the molecular weight of 1645Da is obtained.

(2) The absolute pressure of the reaction system in the step (1) is kept at 4000Pa, the temperature is raised to 230 ℃, the reaction is carried out for 1h, and then the distillation is carried out, thus 534.8g of white crystalline L-lactide is obtained, the yield is 71%, the optical purity is 96.4%, and the content of free lactic acid is 0.33wt%.

Example 24

Synthesis of lactide from lactic acid:

(1) 1000g of an aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) was added to a three-necked flask, 5g of a [4] methyl-substituted n-butoxy zinc complex was added thereto, and the mixture was stirred and reacted at 25 ℃ and 3000PaA in a nitrogen atmosphere for 2 hours, and then heated to 180 ℃ at a rate of 2 ℃/min and stirred and reacted for 3 hours to obtain a lactic acid oligomer having a molecular weight of 1511 Da.

(2) Controlling the absolute pressure of the reaction system in the step (1) to be less than 3000Pa, raising the temperature to 230 ℃, reacting for 1h, and then distilling to obtain 571.5g of white crystalline L-lactide, wherein the yield is 76%, the optical purity is 96.0%, and the content of free lactic acid is 0.26wt%.

Example 25

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) is added into a three-neck flask, 10g of [5] ethyl substituted phenoxyzinc complex is added, stirring reaction is carried out for 2h at 25 ℃ under the nitrogen atmosphere of 3000PaA, then the temperature is increased to 180 ℃ at the speed of 2 ℃/min, stirring reaction is carried out for 3h, and lactic acid oligomer with the molecular weight of 1475Da is obtained.

(2) Controlling the absolute pressure of the reaction system in the step (1) to be less than 3000Pa, raising the temperature to 230 ℃, reacting for 1h, and then distilling to obtain 616.5g of white crystalline L-lactide, wherein the yield is 82%, the optical purity is 95.1%, and the content of free lactic acid is 0.31wt%.

Example 26

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) is added into a three-neck flask, 1g of [6] ethyl substituted cyclohexyloxy zinc complex is added, stirring reaction is carried out for 3h at 25 ℃ and 3000PAa in nitrogen atmosphere, then the temperature is increased to 180 ℃ at the speed of 2 ℃/min, stirring reaction is carried out for 4h, and lactic acid oligomer with the molecular weight of 1642Da is obtained.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 2000Pa, raising the temperature to 230 ℃, reacting for 1h, and then distilling to obtain 581.3g of white crystalline L-lactide, wherein the yield is 77%, the optical purity is 97.1%, and the content of free lactic acid is 0.21wt%.

Example 27

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) is added into a three-neck flask, 1g of [7] cyclohexyl substituted zinc ethoxide complex is added, stirring reaction is carried out for 3h at 25 ℃ under the nitrogen atmosphere of 3000PaA, then the temperature is increased to 180 ℃ at the speed of 2 ℃/min, stirring reaction is carried out for 4h, and lactic acid oligomer with the molecular weight of 1635Da is obtained.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 230 ℃, reacting for 1h, and then distilling to obtain 654.0g of white crystalline L-lactide, wherein the yield is 87%, the optical purity is 97.5%, and the content of free lactic acid is 0.65wt%.

Example 28

Synthesis of lactide from lactic acid:

(1) 1000g of an aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) was added to a three-necked flask, 0.5g of [8] cyclohexyl-substituted zinc isopropoxide complex was added thereto, and the mixture was stirred and reacted at 25 ℃ and 3000PaA in a nitrogen atmosphere for 3 hours, and then heated to 180 ℃ at a rate of 2 ℃/min for 4 hours to obtain a lactic acid oligomer having a molecular weight of 1603 Da.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain 607.5g of white crystalline L-lactide, wherein the yield is 81%, the optical purity is 97.7%, and the content of free lactic acid is 0.90wt%.

Example 29

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) was added to a three-necked flask, 0.5g of [9] methyl-substituted methoxymagnesium complex was added thereto, and the mixture was stirred and reacted at 25 ℃ and 3000PaA in a nitrogen atmosphere for 3 hours, and then heated to 180 ℃ at a rate of 2 ℃/min and stirred and reacted for 4 hours to obtain a lactic acid oligomer having a molecular weight of 1610 Da.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain 585.8g of white crystalline L-lactide, wherein the yield is 78%, the optical purity is 97.0%, and the content of free lactic acid is 0.74wt%.

Example 30

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) was added to a three-necked flask, 0.5g of [10] methyl-substituted ethoxymagnesium complex was added thereto, and the mixture was stirred and reacted at 25 ℃ and 3000PaA in a nitrogen atmosphere for 3 hours, and then heated to 180 ℃ at a rate of 2 ℃/min and stirred and reacted for 4 hours to obtain a lactic acid oligomer having a molecular weight of 1609 Da.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain white crystalline L-lactide 572.2g, wherein the yield is 76%, the optical purity is 96.9%, and the content of free lactic acid is 0.85wt%.

Example 31

Synthesis of lactide from lactic acid:

(1) 1000g of an aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) was added to a three-necked flask, 0.5g of [11] methyl-substituted magnesium isopropoxide complex was added thereto, and the mixture was stirred and reacted at 25 ℃ and 3000PaA in a nitrogen atmosphere for 3 hours, and then heated to 180 ℃ at a rate of 2 ℃/min and stirred and reacted for 4 hours to obtain a lactic acid oligomer having a molecular weight of 1618 Da.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain 592.3g of white crystalline L-lactide, wherein the yield is 79%, the optical purity is 96.6%, and the content of free lactic acid is 0.86wt%.

Example 32

Synthesis of lactide from lactic acid:

(1) 1000g of an aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) was added to a three-necked flask, 0.5g of [12] methyl-substituted n-butoxy magnesium complex was added thereto, and the mixture was stirred and reacted at 25 ℃ and 3000PaA in a nitrogen atmosphere for 3 hours, and then heated to 180 ℃ at a rate of 2 ℃/min and stirred and reacted for 4 hours to obtain a lactic acid oligomer having a molecular weight of 1622 Da.

(2) Controlling the absolute reaction pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain 630.2g of white crystalline L-lactide, wherein the yield is 84%, the optical purity is 97.2%, and the content of free lactic acid is 0.88wt%.

Example 33

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) is added into a three-neck flask, 0.5g of [13] ethyl substituted phenoloxy magnesium complex is added, stirring reaction is carried out for 3h at 25 ℃ and under the nitrogen atmosphere of 3000PaA, then the temperature is raised to 180 ℃ at the speed of 2 ℃/min, stirring reaction is carried out for 4h, and lactic acid oligomer with the molecular weight of 1580Da is obtained.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain 597.2g of white crystalline L-lactide, wherein the yield is 79.6%, the optical purity is 97.7%, and the content of free lactic acid is 0.83wt%.

Example 34

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) is added into a three-neck flask, 0.5g of [14] ethyl substituted cyclohexyloxy magnesium complex is added, stirring reaction is carried out for 3h at 25 ℃ and 3000PaA in a nitrogen atmosphere, then the temperature is increased to 180 ℃ at the speed of 2 ℃/min, stirring reaction is carried out for 4h, and lactic acid oligomer with the molecular weight of 1660Da is obtained.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain 642.3g of white crystalline L-lactide, wherein the yield is 85.7%, the optical purity is 97.1%, and the content of free lactic acid is 0.57wt%.

Example 35

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) is added into a three-neck flask, 0.5g of [15] ethyl-substituted cyclohexyloxy magnesium complex is added, the mixture is stirred and reacted for 3 hours at 25 ℃ and 3000PaA in a nitrogen atmosphere, and then the temperature is increased to 180 ℃ at the speed of 2 ℃/min, the mixture is stirred and reacted for 4 hours, and the lactic acid oligomer with the molecular weight of 1640Da is obtained.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain 638.3g of white crystalline L-lactide, wherein the yield is 85.1%, the optical purity is 97.9%, and the content of free lactic acid is 0.61wt%.

Example 36

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) is added into a three-neck flask, 0.5g of [16] ethyl substituted cyclohexyloxy magnesium complex is added, stirring reaction is carried out for 3h at 25 ℃ and 3000PaA in a nitrogen atmosphere, then the temperature is increased to 180 ℃ at the speed of 2 ℃/min, stirring reaction is carried out for 4h, and lactic acid oligomer with the molecular weight of 1550Da is obtained.

(2) Controlling the absolute reaction pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain 666.3g of white crystalline L-lactide, wherein the yield is 88.8%, the optical purity is 97.7%, and the content of free lactic acid is 0.69wt%.

Comparative example 1

1) Synthesizing 2- (2-hydroxyethyl) magnesium bromide shown as the following formula:

to a dry schlenk bottle, a stirrer and active magnesium powder (0.316g, 13mmol) were added, and replaced three times with nitrogen. Then 10mL of a 1mol/L solution of 1- (2-bromophenyl) ethanol in anhydrous THF was added dropwise over 30min, followed by reaction at 60 ℃ for 3h. And after the reaction is finished, cooling to room temperature, standing for liquid separation, taking supernatant liquor, and removing the solvent to obtain the 2- (2-hydroxyethyl) magnesium bromide.

2) Synthesizing a 2-hydroxyethyl substituted aminopyridine ligand I shown in the following formula:

2-bromopyridine (1.58g, 10 mmol), niCl ₂ (dppp) ₂ (108.41g, 0.2mmol) and 10mL of anhydrous THF were mixed, followed by addition of 0.01mol of 2- (2-hydroxyethyl) magnesium bromide prepared in step 1), and then reacted at 5 ℃ for 6 hours. The reaction mixture was quenched by addition of 20mL of water and extracted with ethyl acetate, and the combined organic phases were Na ₂ SO ₄ Drying, filtering and concentrating under reduced pressure, purifying by n-pentane/ethyl acetate column, and vacuum drying to obtain 2-hydroxyethyl substituted aminopyridine ligand I (1.791 g, yield 90%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ8.37(d,1H),δ8.05(d,1H),δ7.47(dd,1H),δ7.43(dd,1H),δ7.38(dd,1H),δ7.34(dd,1H),δ7.14(dd,1H),δ6.90(dd,1H),δ5.17(s,1H),δ4.98(td,1H),δ1.49(d,3H).

3) Synthesizing a 2-hydroxyethyl methoxy zinc complex [17]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.425g, 1.1mmol) and 13mL of anhydrous THF were mixed well with stirring, and 2-hydroxyethyl substituted aminopyridine ligand I (0.199g, 1mmol) prepared in step 2 was added thereto, and reacted at 25 ℃ for 7 hours, and anhydrous methanol (0.048g, 1.5mmol) was added to the reaction solution, and the reaction was further stirred at 25 ℃ for 5 hours. Filtering to remove substances, removing the solvent by decompression, and separating by using a solvent with a volume ratio of 1:5, recrystallizing the tetrahydrofuran/normal hexane mixed solution to obtain the target product (0.204 g, yield 69%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ8.56(dd,1H),δ8.05(dd,1H),δ7.82(dd,1H),δ7.47(dd,1H),δ7.43(dd,1H),δ7.38(dd,1H),δ7.34(dd,1H),δ6.95(dd,1H),δ4.98(td,1H),δ3.39(s,3H),δ1.49(s,3H).

The complex [17] is subjected to hydrolysis resistance test, and after 1 hour, the nuclear magnetic result changes, so that hydrolysis products are generated; and (4) stability testing, wherein after the mixture is placed for 1h in an open manner, the nuclear magnetic result changes, and new substances are generated.

4) Synthesis of lactide from lactic acid:

(1) 1000g of an aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) was added to a three-necked flask, 0.5g of [17] 2-hydroxyethyl methoxy zinc complex was added thereto, and the mixture was stirred and reacted at 25 ℃ under 3000Pa in a nitrogen atmosphere for 3 hours, and then heated to 180 ℃ at a rate of 2 ℃/min and stirred and reacted for 6 hours, whereby only a lactic acid oligomer having a molecular weight of 800Da was obtained.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain 361.5g of white crystalline L-lactide, wherein the yield is 48.2%, the optical purity is 95.5%, and the content of free lactic acid is 33.5wt%.

Comparative example 2

1) Synthesizing 2- (N-methylaniline) magnesium bromide shown as the following formula:

to a dry schlenk bottle, a stirrer and active magnesium powder (0.316g, 13mmol) were added, and replaced three times with nitrogen. Then 10mL of an anhydrous THF solution of 1 mol/L2-bromo-N-methylaniline was added dropwise over 30min, followed by reaction at 50 ℃ for 2h. And after the reaction is finished, cooling to room temperature, standing for liquid separation, taking supernatant liquor, and removing a solvent to obtain the 2- (N-methylaniline) magnesium bromide.

2) Synthesis of methyl-substituted amino 2-phenyl ligand J of the formula:

bromobenzene (1.57g, 10mmol) and NiCl were mixed ₂ (dppp) ₂ (108.41g, 0.2mmol) and 10mL of anhydrous THF were mixed, followed by addition of 0.01mol of 2- (N-methylaniline) magnesium bromide prepared in step 1), followed by reaction at 2 ℃ for 8 hours. The reaction mixture was quenched by addition of 20mL of water and extracted with ethyl acetate, and the combined organic phases were Na ₂ SO ₄ Drying, filtering and concentrating under reduced pressure, purifying with n-pentane/ethyl acetate column, and vacuum drying to obtain methyl-substituted amino 2-phenyl ligand J (1.665 g, 91% yield).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ8.04(dd,1H),δ7.40-7.43(m,4H),δ7.08(dd,2H),δ7.03(dd,1H),δ6.90(t,1H),δ6.82(s,1H),δ3.01(s,3H).

3) Synthesizing a methyl-substituted methoxy zinc complex [18]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.425g, 1.1mmol) and 15mL of anhydrous THF were stirred and mixed well, and then methyl-substituted amino 2-phenyl ligand A (0.183g, 1mmol) prepared in step 2 was added and reacted at 28 ℃ for 7 hours,anhydrous methanol (0.048 g, 1.5mmol) was further added to the reaction solution, and the reaction was further stirred at 25 ℃ for 5 hours. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5 to obtain the target product (0.184 g, yield 66%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ8.04(dd,1H),δ7.41-7.43(m,3H),δ7.33(t,1H),δ7.08(dd,2H),δ6.86-6.90(dd,2H),δ3.39(s,3H),δ2.78(s,3H).

The complex [18] is subjected to hydrolysis resistance test, the nuclear magnetism result changes within 1h, and hydrolysis products are generated; and (4) testing stability, wherein the nuclear magnetic result changes after the film is placed in an open place for 1h, and new substances are generated.

4) Synthesis of lactide from lactic acid:

(1) 1000g of an aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) was charged into a three-necked flask, 0.5g of [18] methyl-substituted methoxy zinc complex was added thereto, and the mixture was stirred and reacted at 25 ℃ under a nitrogen atmosphere of 3000PaA for 3 hours, and then heated to 180 ℃ at a rate of 2 ℃/min for 8 hours with stirring, to obtain only a lactic acid oligomer having a molecular weight of 560 Da.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000PaA, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain 311.3g of white crystalline L-lactide, wherein the yield is 41.5%, the optical purity is 94.6%, and the content of free lactic acid is 46.5wt%.

Comparative example 3

1) The ligand synthesis procedure was the same as in example 1.

2) Synthesizing methyl-substituted silicon amino zinc complex [19]:

a dry schlenk flask was charged with a stir bar, replaced three times with nitrogen, and then Zn [ N (SiMe) was added ₃ ) ₂ ] ₂ (0.425g, 1.1mmol) and 11mL of anhydrous THF were mixed with stirring, and methyl-substituted aminopyridine ligand A (0.184g, 1mmol) prepared in example 1 was added and reacted at 30 ℃ for 6h. Filtering to remove impurities, and removing the solvent under reduced pressure, wherein the volume ratio of the solvent to the filtrate is 1:5 is tetrahydro ofThe furan/n-hexane mixed solution was recrystallized to obtain the target product (0.323 g, yield 76%).

¹ H NMR(400MHz,CDCl ₃ ,298K)δ9.25(dd,1H),δ8.56(dd,1H),δ7.82(dd,1H),δ7.33-7.38(m,2H),δ6.95(t,1H),δ6.85-6.86(dd,2H),δ2.78(s,3H),δ0.08(s,18H).

The complex [19] is tested for hydrolysis resistance, and after 1 hour, the nuclear magnetic result changes, and hydrolysis products are generated; and (4) testing stability, wherein the nuclear magnetic result changes after the film is placed in an open place for 1h, and new substances are generated.

Synthesis of lactide from lactic acid:

(1) 1000g of L-lactic acid aqueous solution (90 wt%, optical purity > 99.5%) was added to a three-necked flask, 0.5g of [19] methyl-substituted silicon amino zinc complex was added thereto, and the mixture was stirred and reacted at 25 ℃ and 3000Pa for 3 hours, and then heated to 180 ℃ at a rate of 2 ℃/min and stirred and reacted for 24 hours, thereby obtaining only a lactic acid oligomer having a molecular weight of 200 Da.

(2) Controlling the absolute reaction pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain only a small amount of white crystalline L-lactide 22.1g, wherein the yield is 2.9%, the optical purity is 93.5%, and the content of free lactic acid is 66.5wt%.

Comparative example 4

Synthesis of lactide from lactic acid:

the complex [20] is tested for hydrolysis resistance, and nuclear magnetic results are unchanged after 24 hours; stability test, the nuclear magnetic result is not changed after the complex is placed in the open air for 3 days, which proves that the complex prepared by the embodiment has good hydrolysis resistance and stability.

(1) 1000g of an aqueous solution of L-lactic acid (90 wt%, optical purity > 99.5%) was charged into a three-necked flask, 0.5g of a [20] methyl-substituted methoxy copper complex was added thereto, and the mixture was stirred and reacted at 25 ℃ under a nitrogen atmosphere of 3000PaA for 3 hours, and then heated to 180 ℃ at a rate of 2 ℃/min and stirred and reacted for 8 hours, whereby only a lactic acid oligomer having a molecular weight of 600DaA was obtained.

(2) Controlling the absolute reaction pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain only 62.1g of a small amount of white crystalline L-lactide, wherein the yield is 8.3%, the optical purity is 94.1%, and the content of free lactic acid is 35.1wt%.

Comparative example 5

Synthesis of lactide from lactic acid:

the hydrolysis resistance of the complex [21] is tested, and after 1 hour, the nuclear magnetic result changes, and hydrolysis products are generated; and (4) stability testing, wherein after the mixture is placed for 1h in an open manner, the nuclear magnetic result changes, and new substances are generated.

(1) 1000g of an aqueous L-lactic acid solution (90 wt%, optical purity > 99.5%) was charged into a three-necked flask, and 0.5g of [21] bis (2-pyridyl) methyl-substituted aminophenoxymagnesium complex (prepared according to CN 108558932A) was added thereto, and the mixture was stirred and reacted at 25 ℃ under a nitrogen atmosphere of 3000Pa for 3 hours, and then heated to 180 ℃ at a rate of 2 ℃/min and stirred and reacted for 24 hours, to obtain only a lactic acid oligomer having a molecular weight of 180 Da.

(2) Controlling the reaction absolute pressure of the reaction system in the step (1) to be 1000Pa, raising the temperature to 200 ℃, reacting for 1h, and then distilling to obtain only 18.8g of a small amount of white crystalline L-lactide, wherein the yield is 2.5%, the optical purity is 94.6%, and the content of free lactic acid is 65.1wt%.

Claims (9)

1. A catalyst for synthesizing lactide by lactic acid is characterized by having a structure shown as a formula (1):

in the formula, R ₁ Represents hydrogen, alkyl with a C1-C20 straight chain, branched chain or cyclic structure, mono-or poly-aryl substituted alkyl with C7-C30, halogen; preferably C1-C10 linear, branched or cyclic alkyl,C7-C18 mono-or polyaryl substituted alkyl, halogen; more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl, phenyl, benzyl, chlorine, bromine, iodine, etc.; more preferably methyl, ethyl, isopropyl, cyclohexyl;

R ₂ represents C1-C10 linear chain, branched chain or cyclic structure alkyl, C7-C30 mono-or poly-aryl substituted alkyl; preferably C1-C8 linear chain, branched chain or cyclic structure alkyl, C7-C18 mono-or poly-aryl substituted alkyl; more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclooctyl; more preferably methyl, ethyl, isopropyl, cyclohexyl;

m is Mg, ca or Zn, preferably Zn.

2. The catalyst for lactic acid synthesis of lactide according to claim 1, wherein the catalyst for lactic acid synthesis of lactide is any one of complexes represented by the following structural formulas [1] - [16]:

3. a method for preparing the catalyst for lactide synthesis from lactic acid according to claim 1 or 2, characterized by comprising the steps of:

1) Mixing amino-substituted aryl bromide, metal magnesium and a solvent A for reaction to prepare amino-substituted aryl magnesium bromide;

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

3) Mixing the aminopyridine ligand in the step 2), the hexamethyldisilazane-based amino metal complex and a solvent C for coordination reaction, and then adding an alcohol compound for alkoxylation reaction to prepare the catalyst for synthesizing lactide from lactic acid.

4. The production method according to claim 3, wherein in step 1), the amino-substituted aryl bromide is any one selected from compounds having a structure represented by formula (2):

in the formula, R ₁ Definition of R in the formula (1) ₁ The same;

in the step 1), the molar ratio of the amino-substituted aryl bromide to the metal magnesium is 1:1-2, preferably 1:1.2-1.3;

in the step 1), the solvent A is at least one selected from tetrahydrofuran and toluene, and is preferably tetrahydrofuran;

the dosage of the solvent A is 1-15 mL/mmol of amino-substituted aryl bromide;

in the step 1), the amino-substituted aryl bromide is preferably added dropwise in a continuous feeding mode, wherein the feeding time is 30-60min, and is preferably 30min;

in the step 1), the reaction is carried out at the temperature of 30-60 ℃, preferably 45-55 ℃ for 2-5h, preferably 2-3h.

5. The method according to claim 3 or 4, wherein the molar ratio of the amino-substituted aryl magnesium bromide to the 2-bromopyridine in the step 2) is 1:1-1.5, preferably 1:1-1.2;

in step 2), the catalyst is selected from 1, 3-bis (diphenylphosphinopropane) nickel dichloride;

the catalyst is used in an amount of 1-5%, preferably 2-3% of the molar amount of the amino-substituted aryl magnesium bromide;

in the step 2), the solvent B is at least one selected from tetrahydrofuran and toluene, and tetrahydrofuran is preferred;

the dosage of the solvent B is 1-15 mL/mmol of amino-substituted aryl magnesium bromide;

in the step 2), the coupling reaction is carried out at the temperature of 0-20 ℃, preferably 0-5 ℃ for 6-12 hours, preferably 6-8 hours.

In the step 2), a water adding quenching process is also included after the reaction is finished;

and adding water for quenching, wherein the adding amount of the water is 1-2 times of the mass of the reaction system.

6. The process according to any one of claims 3 to 5, wherein in step 3), the hexamethyldisilazane-based metal complex has the general formula M [ N (SiMe) ₃ ) ₂ ] ₂ Wherein M represents a metal element, the definition is the same as M in formula (1), and Me represents a methyl group;

the molar ratio of the hexamethyldisilazane-based amino metal complex to the aminopyridine ligand is 1-1.5:1, preferably 1:1.

in the step 3), the solvent C is at least one selected from tetrahydrofuran and toluene, and is preferably tetrahydrofuran;

the amount of solvent C is 5-20mL per mmol of aminopyridine ligand.

In the step 3), the general formula of the alcohol compound is R ₂ OH, wherein R ₂ Definition and R in formula (1) ₂ The same;

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

in the step 3), the coordination reaction is carried out at the temperature of 10-50 ℃, preferably 20-30 ℃ for 6-12 hours, preferably 6-8 hours;

the alkoxylation reaction is carried out at a temperature of 10-50 ℃, preferably 20-30 ℃ for 4-8h, preferably 4h.

7. A process for synthesizing lactide from lactic acid, which comprises using an aqueous solution of lactic acid as a starting material, subjecting the resulting mixture to a dehydration polycondensation reaction to produce a lactic acid oligomer and then to a high-temperature depolymerization reaction under the action of the catalyst according to claim 1 or 2 or the catalyst produced by the production process according to any one of claims 3 to 6.

8. The method of claim 7, wherein the steps comprise:

(1) Mixing lactic acid aqueous solution with a catalyst, stirring and reacting for 1-8h, preferably 2-4h, at the absolute pressure of 1-10kPa, preferably 2-5kPa, and the temperature of 20-50 ℃, preferably 20-30 ℃, and then heating to 120-180 ℃, preferably 150-180 ℃, stirring and reacting for 3-10h, preferably 3-4h, so that lactic acid is dehydrated and polycondensed to generate lactic acid oligomer with the molecular weight of 500-2000 Da;

(2) The reaction system of the step (1) is stirred and reacted for 1-4h, preferably 1-1 h, under the absolute pressure of 1-4kPa, preferably 1-2kPa, and at the temperature of 180-250 ℃, preferably 200-230 ℃, so that the lactic acid oligomer is depolymerized at high temperature to prepare the lactide.

9. The method according to claim 8, wherein in step (1), the aqueous solution of lactic acid has a concentration of 60 to 100 wt.%, preferably 90 to 95 wt.%;

the lactic acid is L-lactic acid and/or D-lactic acid, and the optical purity is more than 99.5%;

in the step (1), the mass ratio of the catalyst to the aqueous solution of lactic acid is 1-5000, and the more preferable mass ratio is 1;

in the step (1), the temperature is increased at the rate of 0.5-2 ℃/min, preferably 1 ℃/min;

in the steps (1) and (2), stirring is carried out at the rotating speed of 50-400r/min, preferably 150-250r/min.