A method for the stereoselective preparation of racemic lactide from racemic lactic acid

Abstract

The application provides a method for stereoselectively preparing racemic lactide from racemic lactic acid, and relates to the technical field of catalysts.The application provides application of a molecular sieve in catalysis of stereoselective preparation of racemic lactide from racemic lactic acid, and the molecular sieve is H-Beta molecular sieve or H-ZSM-5 molecular sieve.The application uses H-Beta or H-ZSM-5 molecular sieve in catalysis of stereoselective preparation of racemic lactide from racemic lactic acid, so that the selectivity of obtaining meso-lactide from racemic lactic acid is reduced, the selectivity of obtaining Rac a high proportion of racemic lactide from racemic lactic acid is increased D / L LD is increased, and the selectivity of obtaining Meso LD is further reduced, and the selectivity is increased.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of catalysts, in particular to a method for stereoselectively preparing racemic lactide from racemic lactic acid. BACKGROUND

[0002] Since the invention of plastics, plastic products have become an indispensable part of modern life and play a vital role in the fields of industry, agriculture, medicine and packaging. However, most plastic products are made from petrochemical raw materials and face challenges in degradation and recycling. In the face of the continuous depletion of non-renewable energy sources and increasingly serious environmental problems, the production and use of plastics are contrary to the concept of contemporary sustainable development. Biobased degradable polymer plastic products provide an important way to solve the urgent problem of plastic pollution. At present, more than 20 different types of biobased degradable polymers have been applied, among which polylactic acid (PLA) is one of the main synthetic biobased plastics on the market.

[0003] At present, the industrial production of high-quality PLA mainly relies on the ring-opening polymerization of the intermediate lactide (LD). In early studies, the prepolymerization and back-biting process is the key step for the conversion of LA to LD, and this process requires high temperature and vacuum to remove water and achieve product separation, inevitably causing energy and time consumption and increasing polymer waste. At present, a series of studies on the shape-selective ability of molecular sieve catalysts are applied to promote the production of LD, including catalytic processes, development of catalysts and exploration of reaction conditions. However, the production cost of LA accounts for about half of the entire production process of PLA, and the traditional fermentation method for producing LA has a long cycle and a complex purification process, which is not conducive to the large-scale production and application of polylactic acid products.

[0004] Chemical catalytic method helps to directly convert biomass into lactic acid monomer, which not only can quickly and efficiently achieve the production of lactic acid to meet market demand, but also greatly reduces the production cost of polylactic acid precursor. However, chemical catalytic conversion will simultaneously generate L -LA and D -LA enantiomers, thereby producing a racemic solution Rac -LA). In theory, Rac -LA can be converted into three stereoisomers of LD: DD -LD, LL -LD( D / L- LD, racemic type) and Meso -LD (meso type). Among them, due to the Meso-LD has easy hydrolysis and influences on the regularity of PLA, which can cause differences in the performance of plastic products and application limitations, so meso-lactide is considered as an undesirable by-product. In summary, the application of LA obtained by chemical catalytic conversion in the synthesis of PLA is still limited, and it is necessary to reduce Meso The presence of LD is an important factor to achieve Rac The conversion and upgrading of LA is an important link to promote the application of PLA plastic products in the market. SUMMARY

[0005] Therefore, the purpose of the present application is to provide a method for stereoselectively preparing rac-lactide from racemic lactic acid. The present application uses molecular sieve (H-Beta molecular sieve or H-ZSM-5 molecular sieve) to catalyze the stereoselective preparation of rac-lactide from racemic lactic acid, which can obtain Rac -LA stereoselectively obtains a high proportion of rac-lactide D / L- LD, and reduces the selectivity of meso-lactide.

[0006] In order to achieve the above-mentioned purpose of the application, the present application provides the following technical solutions:

[0007] The present application provides an application of a molecular sieve in catalyzing the stereoselective preparation of rac-lactide from racemic lactic acid, wherein the molecular sieve is H-Beta molecular sieve or H-ZSM-5 molecular sieve.

[0008] Preferably, when the molecular sieve is H-Beta molecular sieve, the application further comprises: before the catalysis, the H-Beta molecular sieve is subjected to a regularizing treatment, and the regularizing treatment comprises the following steps:

[0009] (a) mixing the H-Beta molecular sieve with a tetraethylammonium hydroxide aqueous solution to perform a first hydrothermal treatment, to obtain a crystalline Beta phase dissolved mixture;

[0010] (b) mixing the crystalline Beta phase dissolved mixture with ammonium fluoride to perform a second hydrothermal treatment, to obtain a recrystallized H-Beta phase gel;

[0011] (c) sequentially performing washing, drying and calcination on the H-Beta phase gel, to obtain the regularized H-Beta molecular sieve.

[0012] Preferably, the H-Beta molecular sieve is based on SiO2 and Al2O3, and the mixture obtained in step (a) satisfies the molar ratio of SiO2:Al2O3:TEAOH:H2O = 1.0:0.04:0.5:7.5, and the mixture obtained in step (b) satisfies the molar ratio of SiO2:Al2O3:TEAOH:H2O:NH4F = 1.0:0.04:0.5:7.5:0.5.

[0013] Preferably, the temperature of the first hydrothermal treatment is 140°C and the time is 45 min; the temperature of the second hydrothermal treatment is 140°C and the time is 24 h; the calcination includes performing a first calcination and a second calcination in sequence, the temperature of the first calcination is 200°C and the time is 2 h, and the temperature of the second calcination is 550°C and the time is 6 h.

[0014] This invention provides a method for the stereoselective preparation of racemic lactide from racemic lactic acid, comprising the following steps:

[0015] An esterification reaction is carried out by mixing racemic lactic acid solution, molecular sieve catalyst and organic solvent to obtain a mixture of lactide with different configurations, wherein the mixture of lactide with different configurations includes racemic lactide; the molecular sieve catalyst is the molecular sieve used in the above technical solution.

[0016] Preferably, the lactic acid in the racemic lactic acid solution comprises lactic acid monomers and lactic acid dimers, wherein the contents of the lactic acid monomers and lactic acid dimers in the racemic lactic acid solution are 13.2-100% and 0-36.1%, respectively.

[0017] Preferably, the mass ratio of lactic acid to molecular sieve catalyst in the racemic lactic acid solution is 0.9 to 9:1.

[0018] Preferably, the organic solvent is toluene, o-xylene, or mesitylene.

[0019] Preferably, the esterification reaction is carried out at a temperature of 140–180°C for a time of 10 min–3 h.

[0020] Preferably, the temperature of the esterification reaction is 160–180°C.

[0021] This invention provides the application of a molecular sieve in the stereoselective catalytic preparation of racemic lactate from racemic lactic acid, wherein the molecular sieve is an H-Beta molecular sieve or an H-ZSM-5 molecular sieve. This invention utilizes a molecular sieve (H-Beta molecular sieve or H-ZSM-5 molecular sieve) in the stereoselective catalytic preparation of racemic lactate from racemic lactic acid, which can reduce the degradation of lactic acid by factors such as the formation of racemic lactate. Rac -LA) to obtain meso lactide ( Meso-LD) selectivity, derived from racemic lactic acid Rac -LA stereoselectivity yields a high proportion of racemic lactide D / L- LD. Furthermore, this invention, by performing a regularization treatment (i.e., structural reconstruction) on the H-Beta molecular sieve, results in a more complete pore structure, providing higher stereoselectivity and improving the product's... Meso -LD distribution is further reduced, and stereoselectivity is improved.

[0022] This invention provides a method for the stereoselective preparation of racemic lactide from racemic lactic acid, comprising the following steps: mixing a racemic lactic acid solution, a molecular sieve catalyst, and an organic solvent to carry out an esterification reaction to obtain racemic lactide. The molecular sieve catalyst is the molecular sieve used in the above-described technical solutions. This invention uses racemic lactic acid as a substrate and the aforementioned molecular sieve as a catalyst to synthesize lactide (LD) in a one-step process, resulting in a high proportion of racemic lactide in the lactide product. The preparation method provided by this invention is simple, uses inexpensive and readily available raw materials, has low production costs, and can be mass-produced.

[0023] In the embodiments of the present invention, a series of materials with different dimer distributions are used. Rac Using LA as a substrate, lactide (LD) products exhibiting different enantiomeric distributions were synthesized in a one-step process, demonstrating that the stereoisomer distribution of LD is tunable and that the molecular sieve channels are open. X The initial content of -L2A (lactic acid dimer) plays a crucial role; increased temperature promotes the rapid conversion of lactic acid monomer (LA) into... X -L2A, which then selectively diffuses into the micropores to form LD, allows for a simple, rapid, and economical process without the need for additional cumbersome enantiomer separation steps. Rac -LA stereoselectively obtains a high proportion of racemic lactide ( D / L- LD), with high product utilization rate.

[0024] The results of the examples show that, using the method of the present invention with H-Beta molecular sieve as a catalyst, racemic lactide is prepared with high selectivity (…). D / L- LD / Meso -LD) ranges from 1.39 to 3.60. Attached Figure Description

[0025] Figure 1 Examples 1-2 illustrate the preparation of lactide using different racemic lactic acid solutions. 1 H liquid NMR spectrum ( 1 HNMR, solvent is d -DMSO);

[0026] Figure 2The preparation of lactide using different racemic lactic acid solutions in Examples 1-2 and Comparative Example 1 1 H liquid NMR spectrum ( 1 H NMR, solvent is d -CDCl3);

[0027] Figure 3 The high-performance liquid chromatography (HPLC) spectra of lactide prepared using different racemic lactic acid solutions in Examples 1-2 are shown below.

[0028] Figure 4 Stereoisomer distribution diagram for lactide prepared from racemic lactic acid solutions with different dimer contents in Comparative Example 3;

[0029] Figure 5 The diagram shows the change in the proportion of lactic acid dimer and lactide stereoisomers in the preparation of lactide using H-Beta molecular sieves for Comparative Example 4.

[0030] Figure 6 Comparative Example 5 contains different X A graph showing the relationship between the proportion of stereoisomers and the dimer content when using racemic lactic acid solutions with L2A distribution for the preparation of lactide.

[0031] Figure 7 The diagram shows the proportion of stereoisomers of lactide products obtained at different temperatures using different racemic lactic acid solutions from Examples 1-3.

[0032] Figure 8 XRD comparison diagram of H-Beta-R molecular sieve after structural reconstruction in Example 5 and commercial H-Beta molecular sieve;

[0033] Figure 9 A comparison of the pyridine-infrared (PY-IR) spectra of the H-Beta-R molecular sieve after structural reconstruction in Example 5 and the commercial H-Beta molecular sieve.

[0034] Figure 10 The distribution of stereoisomers at different reaction times at 140°C when the H-Beta-R molecular sieve with the reconstructed structure from Example 5 was used for the preparation of lactide. Detailed Implementation

[0035] This invention provides an application of a molecular sieve in the stereoselective catalytic preparation of racemic lactide from racemic lactic acid, wherein the molecular sieve is an H-Beta molecular sieve or an H-ZSM-5 molecular sieve.

[0036] This invention does not have specific requirements regarding the source of the H-Beta and H-ZSM-5 molecular sieves; they can be obtained from commercially available products or prepared using methods well-known to those skilled in the art. This invention utilizes H-Beta or H-ZSM-5 molecular sieves in the stereoselective catalytic preparation of racemic lactic acid from racemic lactate, which can reduce the degradation of racemic lactic acid (… Rac -LA) to obtain meso lactide ( Meso -LD) selectivity, derived from racemic lactic acid Rac -LA stereoselectivity yields a high proportion of racemic lactide D / L- LD.

[0037] In this invention, when the molecular sieve is an H-Beta molecular sieve, the application preferably further includes: performing a regularization treatment on the H-Beta molecular sieve before catalysis, wherein the regularization treatment preferably includes the following steps:

[0038] (a) The H-Beta molecular sieve is mixed with an aqueous solution of tetraethylammonium hydroxide and subjected to a first hydrothermal treatment to obtain a mixture in which the crystalline Beta phase is dissolved;

[0039] (b) The mixture of the dissolved crystalline Beta phase is mixed with ammonium fluoride and subjected to a second hydrothermal treatment to obtain a recrystallized H-Beta phase gel;

[0040] (c) The H-Beta phase gel is washed, dried and calcined in sequence to obtain a regularized H-Beta molecular sieve.

[0041] In this invention, the tetraethylammonium hydroxide dissolves the molecular sieve and simultaneously serves as a template agent for recrystallization. In this invention, the H-Beta molecular sieve is based on SiO2 and Al2O3, and the mixture obtained in step (a) preferably satisfies the molar ratio: SiO2:Al2O3:TEAOH:H2O = 1.0:0.04:0.5:7.5, where TEAOH represents tetraethylammonium hydroxide. In this invention, the mixing method in step (a) is preferably: adding the H-Beta molecular sieve to an aqueous solution of tetraethylammonium hydroxide for heat treatment; the heat treatment temperature is preferably 70°C. This invention removes some water through the heat treatment, obtaining a mixture satisfying the above molar ratio, while simultaneously achieving preliminary dissolution.

[0042] In this invention, the temperature of the first hydrothermal treatment is preferably 140°C, the time is preferably 45 min, the first hydrothermal treatment is preferably a static hydrothermal treatment, and the first hydrothermal treatment is preferably carried out in a reaction vessel lined with polytetrafluoroethylene. In this invention, the first hydrothermal treatment is a high-temperature hydrothermal treatment to dissolve the crystalline H-Beta.

[0043] In this invention, ammonium fluoride (NH4F) acts as a mineralizing agent to recrystallize the dissolved H-Beta. Preferably, ammonium fluoride is added to the mixture in which the crystalline Beta phase is dissolved. In this invention, the H-Beta molecular sieve, based on SiO2 and Al2O3, preferably satisfies the molar ratio of the mixture obtained in step (b): SiO2:Al2O3:TEAOH:H2O:NH4F = 1.0:0.04:0.5:7.5:0.5. In this invention, the temperature of the second hydrothermal treatment is preferably 140°C, the time is preferably 24 hours, and the second hydrothermal treatment is preferably a static hydrothermal treatment.

[0044] In this invention, the washing is preferably centrifugal washing; the calcination preferably includes a first calcination and a second calcination performed sequentially, wherein the temperature of the first calcination is preferably 200°C and the time is preferably 2 hours, and the temperature of the second calcination is preferably 550°C and the time is preferably 6 hours. The calcination is preferably carried out in an air atmosphere, and the heating rate is preferably 1°C / min. In this invention, the first calcination and the second calcination are respectively a dehydration stage and a crystallization and shaping stage.

[0045] In this invention, the regularized H-Beta molecular sieve is denoted as H-Beta-R.

[0046] This invention, through regularization treatment (i.e., structural reconstruction) of H-Beta molecular sieves, preserves the basic morphology and pore structure of H-Beta molecular sieves while improving the pore regularity of commercial molecular sieves, forming more Si-O-Al bonds, and further enhancing the stereoselectivity for lactic acid dimers, resulting in higher product concentrations. Meso The distribution of -LD further decreased.

[0047] This invention provides a method for the stereoselective preparation of racemic lactide from racemic lactic acid, comprising the following steps:

[0048] An esterification reaction is carried out by mixing racemic lactic acid solution, molecular sieve catalyst and organic solvent to obtain a mixture of lactide with different configurations, wherein the mixture of lactide with different configurations includes racemic lactide; the molecular sieve catalyst is the molecular sieve used in the above technical solution.

[0049] In this invention, the lactic acid in the racemic lactic acid solution preferably comprises lactic acid monomers and lactic acid dimers. The contents of the lactic acid monomers and lactic acid dimers in the racemic lactic acid solution are preferably 13.2–100% and 0–36.1%, respectively, more preferably 13.2–72.7% and 19.7–36.1%, respectively. Specifically, the content of the lactic acid dimers in the racemic lactic acid solution can be 19.7%, 29.2%, 31.1%, 31.2%, 33.9%, 35.7%, and 36.1%. Lactic acid dimers ( X -L2A) has DD -L2A, LL -L2A and DL -L2A's existence form, stereoselectivity is reflected in DL The selectivity of -L2A entering the H-Beta molecular sieve to complete the cyclization reaction is relative to... DD -L2A and LL -L2A decreases, DL -L2A is a dimer form consisting of two different lactic acid monomers linked together, and it is the source of meso lactide formation.

[0050] In this invention, five methods were used to prepare a series of racemic lactic acid solutions with different concentrations and lactic acid dimer distributions. A one-step synthesis of lactide products with different enantiomeric distributions was achieved, verifying that the molecular sieve catalyst can reduce the selectivity of meso lactide in racemic lactic acid solutions. The five methods are as follows:

[0051] Method 1: Racemic lactic acid solution obtained directly by chemical catalytic conversion.

[0052] In this invention, the racemic lactic acid solution directly obtained by the chemical catalytic conversion method contains only lactic acid monomers (equal proportions of D-type lactic acid). D -LA and L-lactic acid L -LA), with a concentration of 7.5 wt%, denoted as 7.5 wt%. Rac -LA chem. .

[0053] This invention does not impose special requirements on the specific operation and conditions of the chemical catalytic conversion method; appropriate methods well known to those skilled in the art can be used. In embodiments of this invention, the chemical catalytic conversion method preferably includes the following steps:

[0054] (1) Mix 1,3-dihydroxyacetone, water and catalyst Sn-DeAl-Beta-50 and perform hydrothermal treatment to obtain a racemic lactic acid solution composed entirely of monomers.

[0055] (2) Rotary evaporate the racemic lactic acid solution obtained in step (1) to remove some water and increase the concentration.

[0056] In this invention, the preferred method for preparing the catalyst Sn-DeAl-Beta-50 is as follows:

[0057] Aluminum atoms were removed from commercial H-Beta molecular sieves by passing them through nitric acid. After filtration, washing and drying, aluminum-removed molecular sieves were obtained, denoted as DeAl-Beta.

[0058] The DeAl-Beta was mixed with SnCl4·5H2O and ground at room temperature in an agate mortar to obtain a grinding mixture.

[0059] The milled mixture was calcined to obtain the catalyst Sn-DeAl-Beta-50, where 50 represents nSi / nSn (mol).

[0060] In this invention, the mass fraction of nitric acid (AR) is preferably 65.0-68.0%, and the ratio of nitric acid to H-Beta molecular sieve is preferably 20 mL:1 g; the temperature for removing aluminum atoms is preferably 80 °C, and the time is preferably 24 h. In this invention, the mass ratio of DeAl-Beta to SnCl4·5H2O is preferably 1:0.1168, and the grinding time is preferably 30 min or more. In this invention, the calcination is preferably carried out in an air atmosphere, including sequentially performing a first-stage calcination and a second-stage calcination. The temperature of the first-stage calcination is preferably 200 °C, and the time is preferably 2 h; the temperature of the second-stage calcination is preferably 550 °C, and the time is preferably 6 h; the heating rate of the calcination is preferably 1 °C / min.

[0061] In this invention, the preferred mass ratio of 1,3-dihydroxyacetone, water, and catalyst Sn-DeAl-Beta-50 is 1:50:1; the hydrothermal treatment is preferably microwave high-temperature hydrothermal treatment, with a preferred temperature of 130°C and a preferred time of 3 hours. In this invention, the removal of some water is intended to obtain a racemic lactic acid solution with a concentration of 7.5 wt%.

[0062] Method 2: Utilize commercially available 90wt% optically active... D -LA solution (referred to as 90wt%) D -LA com. ) and 90wt% L -LA solution (referred to as 90wt%) L -LA com. Mix in a 1:1 (w:w) ratio to form a mixture containing DD -L2A and LL -L2A but does not contain DL -L2A racemic lactic acid solution (named 90wt%) DL -LA com. ); the 90wt%D -LA com. Solution and 90wt% L -LA com. The solution contains lactic acid monomers, dimers, and other oligomers, totaling 90 wt%, with the remainder being water.

[0063] Method 3: Use commercially available 90wt% DL -LA solution (referred to as 90wt%) DL -LA com. ) and commercially available 90wt% Rac -LA solution (referred to as 90wt%) Rac -LA com. When mixed in a certain ratio (w:w), different results are obtained. DL -L2A, DD -L2A, LL The racemic solution in the L2A ratio maintains the racemic nature and content of the monomer throughout the mixing process; the ratios are 0:1, 1:3, 1:1, 3:1, and 1:0. In this invention, a commercially available high-concentration racemic lactic acid solution of 90 wt% is used. Rac -LA com. It contains lactic acid monomers, lactic acid dimers, and small amounts of lactic acid trimers and tetramers, with a total concentration of 90 wt%.

[0064] Method 4: Add 90wt% D -LA com. and 90wt% L -LA com. Pre-treatment at constant temperature for a certain period of time to improve DD -L2A and LL -L2A content.

[0065] In this invention, the pretreatment temperature is preferably 80°C, and after pretreatment, the sample is analyzed using high-performance liquid chromatography (HPLC) to determine the specific components. This pretreatment promotes monomer dehydration to form more dimers, thereby adjusting the dimer content and altering the solution composition.

[0066] Method 5: Add 90wt% Rac -LA com. Pre-treatment at constant temperature for a certain period of time to improve X The content of -L2A, while simultaneously increasing the concentration to 90 wt%. Rac -LA com. 7.5wt% mixed Rac -LA chem Methods to reduce the amount of [something] in the solution XThe relative content of -L2A; the preferred temperature for the pretreatment is 80°C, and the sample is then subjected to high performance liquid chromatography (HPLC) to determine the specific components after the pretreatment.

[0067] Method five adjusts the dimer content through pretreatment and mixing. In this embodiment of the invention, the absolute dimer content in the solution obtained by method five is 19.7%, 26.1%, 31.2%, 36.1%, and 29.2%, respectively, which are expressed as relative values ​​of dimer content to monomer and total dimer content. X -L2A / (LA+ X The percentages of -L2A were 21.3%, 28.7%, 34.6%, 43.0%, and 58.9%, respectively.

[0068] In this invention, the mass ratio of lactic acid to molecular sieve catalyst in the racemic lactic acid solution is preferably 0.9–9:1, more preferably 1.8:1. In this invention, the organic solvent is preferably toluene, o-xylene, or mesitylene, and the preferred volume ratio of the racemic lactic acid solution to the organic solvent is 6 g: 5 mL. In this invention, the preferred order of adding the racemic lactic acid solution, molecular sieve catalyst, and organic solvent is racemic lactic acid solution, molecular sieve catalyst, and organic solvent, from first to last. This invention does not specifically limit the mixing method; any method that ensures uniform mixing of the raw materials is acceptable, such as stirring.

[0069] After mixing, the present invention preferably places a phase settler pre-filled with organic solvent at the top of the reaction apparatus to allow solvent reflux and remove water from the reactants and water generated during the reaction.

[0070] In this invention, the esterification reaction temperature is preferably 140–180°C, more preferably 140°C, 160°C, or 180°C. When the content of lactic acid dimer in the racemic lactic acid solution is 0, the esterification reaction temperature is further preferably 160–180°C. The reaction time is preferably 10 min–3 h. The reaction is preferably carried out under oil bath conditions. In this invention, the esterification reaction temperature corresponds to the selected organic solvent. The esterification reaction temperature is 20°C higher than the boiling point of the organic solvent to ensure reflux. Specifically, when the organic solvent is toluene, the esterification reaction temperature is 140°C; when the organic solvent is o-xylene, the esterification reaction temperature is 160°C; and when the organic solvent is mesitylene, the esterification reaction temperature is 180°C. In this invention, the reaction is preferably carried out under stirring conditions. This invention, based on the boiling point difference of the organic solvent, can change the formation rate and position of the lactic acid dimer.

[0071] In this invention, as the initial lactic acid dimer in the racemic lactic acid solution ( XThe increase in the content of -L2A) in the product Meso The reduced selectivity of -LD is more pronounced, indicating that the distribution of stereoisomers of the product is related to different... X - The degree of ringization achievable with L2A is related. Furthermore, the same... Rac - By reacting the LA substrate at different temperatures and regularizing the catalyst channels, the stereoselectivity of the product can be effectively improved.

[0072] In this invention, after the esterification reaction, a post-treatment is preferably included. The post-treatment method is to cool the reaction solution obtained from the esterification reaction to room temperature and then mix it with acetonitrile. This invention does not specifically limit the cooling method; any cooling method well-known in the art can be used, such as natural cooling. In this invention, the mixing method is preferably ultrasonic or stirring to ensure uniform mixing. After mixing, the resulting mixture is preferably allowed to stand overnight to obtain a homogeneous solution.

[0073] The method provided by this invention can achieve the production of racemic lactic acid. Rac -Laminated lactide preparation with high stereoselectivity D / L- LD.

[0074] To further illustrate the present invention, the method for the stereoselective preparation of racemic lactide from racemic lactic acid provided by the present invention will be described in detail below with reference to examples, but these should not be construed as limiting the scope of protection of the present invention.

[0075] In each embodiment, Rac -LA chem. The racemic lactic acid solution is obtained directly from the chemical catalytic conversion of the carbohydrate 1,3-dihydroxyacetone. The preparation method is as follows:

[0076] Preparation of catalyst Sn-DeAl-Beta-50:

[0077] (1) 1g of commercial H-Beta was treated with 20mL of nitric acid (AR, 65.0~68.0%) to remove aluminum atoms. The treatment temperature was 80℃ and the treatment time was 24h. After filtration, washing and drying, DeAl-Beta was obtained.

[0078] (2) Mix 1g DeAl-Beta with 0.1168g SnCl4·5H2O in an agate mortar and grind at room temperature for more than 30 minutes.

[0079] (3) The above-ground mixture was calcined to obtain Sn-DeAl-Beta-50, where 50 represents n Si / n Sn(mol), the calcination atmosphere is air, the heating program is 1℃ / min, the first stage calcination temperature is 200℃ and the time is 2h, the second stage calcination temperature is 550℃ and the time is 6h.

[0080] preparation Rac -LA chem. :

[0081] (1) Mix 0.1g of 1,3-dihydroxyacetone with 5g of water, add 0.1g of catalyst Sn-DeAl-Beta-50, and perform microwave high-temperature hydrothermal treatment at 130℃ for 3h to obtain a racemic lactic acid solution composed entirely of monomers.

[0082] (2) The above solution was rotary evaporated to remove some water, making the solution concentration 7.5 wt%. The resulting racemic lactic acid solution was recorded as 7.5 wt%. Rac -LA chem. .

[0083] Example 1

[0084] The preparation of lactide using H-Beta molecular sieves was carried out in a 25 mL round-bottom flask. A special phase settler device was used at the top, equipped with a spherical condenser connected to cooling water to remove water from the system. The phase settler was pre-filled with the organic solvent toluene. First, 6 g of 7.5 wt%... Rac -LA chem. Add 250 mg of H-Beta molecular sieve to a round-bottom flask, mix thoroughly at room temperature, add 5 mL of toluene (organic solvent), and place in a preheated oil bath. Heat at 140 °C for 3 hours, then stop heating and disassemble the apparatus. Remove the round-bottom flask from the oil bath and cool to room temperature. Add 10 mL of acetonitrile and sonicate until homogeneous. Let stand overnight to obtain a homogeneous solution. Take 4 mL of the solution, filter through a 0.22 μm microfilter, and place the filtered supernatant in a tube furnace under an inert Ar atmosphere. Heat to 70 °C at a rate of 1 °C / min and dry to completely remove the organic solvents toluene and acetonitrile for later use.

[0085] The dried solid component was added to 0.6 mL of DMSO-d6 and dissolved completely by sonication. The solution was then transferred to a liquid... 1 H NMR ( 1 Quantitative analysis was performed using HNMR to calculate the conversion rate of lactic acid and the yield of lactide, as shown in equations (1) and (2).

[0086] The dried solid component was dissolved by sonication in 0.6 mL of CDCl3, and then dissolved by liquid... 1 H NMR ( 1 The product was qualitatively identified and analyzed by ¹H NMR, and the relative amounts of the product were determined to be racemic lactide.D / L- LD and meso lactide Meso -The existence and relative proportion of LD, stereoisomers D / L- LD / Meso The formula for calculating -LD is shown in equation (3).

[0087]

[0088]

[0089]

[0090] In equations (1) to (3), S and S' respectively represent the use of 1 Peak areas were determined by ¹H NMR using DMSO-d6 and CDCl3 as solvents. Lactic acid conversion and lactide yield were calculated using the results obtained with DMSO-d6 reagent. S represents the area of ​​the characteristic quartet in the methylene region. The chemical shifts of the characteristic quartet in the methylene region of the reactants and products in DMSO-d6 reagent are as follows: D / L- LD and Meso -LD (5.38-5.5ppm); L n A (oligomer center: 5.08-5.18 ppm, oligomer carboxyl end group: 4.88-5.02 ppm, oligomer hydroxyl end group: 4.18-4.22 ppm); LA (4.02-4.15 ppm). The stereoisomer ratio of lactide was calculated using test results obtained by dissolving in CDCl3 reagent, where S' represents the area of ​​the characteristic doublet of the methyl region. The chemical shifts of the characteristic doublet of the methyl region of the stereoisomers of lactide in CDCl3 reagent are as follows: D / L- LD (1.66-1.70ppm) and Meso -LD (1.70-1.74ppm).

[0091] Example 1 utilizes 7.5 wt% Rac -LA chem. Preparation of lactide from racemic lactic acid solution 1 The NMR spectra of H liquid are as follows: Figure 1 ( 1 H NMR, solvent is d -DMSO) and Figure 2 ( 1 H NMR, solvent is d As shown in -CDCl3).

[0092] Depend on Figures 1-2 It can be seen that, through 1¹H NMR analysis showed that the conversion rate of lactic acid was 76%, the yield of lactide was 50%, and the stereoisomer selectivity of lactide was 1.02. This example illustrates that H-Beta molecular sieves do not exhibit heterogeneity for different monomers in the synthesis of lactide from lactic acid monomers. D -LA、 L Stereoselectivity of -LA).

[0093] Example 2

[0094] Following the method of Example 1, a commercially available racemic lactic acid solution (90 wt%) was used. Rac -LA com. The preparation of lactide differs from that in Example 1 in that: in step (1), 6g of 7.5wt% lactide is used. Rac -LA chem. 0.25g H-Beta molecular sieve catalyst was replaced with 0.5g 90wt%. Rac -LA com. 0.25g H-Beta molecular sieve catalyst.

[0095] Example 2 utilizes 90wt% Rac -LA com. Preparation of lactide from racemic lactic acid solution 1 The NMR spectra of H liquid are as follows: Figure 1 ( 1 HNMR, solvent is d -DMSO) and Figure 2 ( 1 HNMR, solvent is d As shown in -CDCl3).

[0096] Depend on Figures 1-2 It can be seen that, through 1 HNMR analysis showed a lactic acid conversion rate of 95% and a lactide yield of 52%, with a stereoisomer selectivity of 1.39 for the lactide product. This example illustrates the uneven stereoisomer distribution within the lactide product. Meso - The stereoselectivity of LD is reduced.

[0097] The high-performance liquid chromatography (HPLC) equipment was an Agilent Corporation instrument with a 210 nm UV detector, and the capillary column was a ZORBAX-C18 (4.6 mm × 250 mm). The chromatographic conditions were: acetonitrile (0.8 mL 85% H3PO4 per L) and water (0.8 mL 85% H3PO4 per L) as the mobile phase. DHA (1,3-dihydroxyacetone) and LA were determined. chem. The elution program was: water / acetonitrile (98 / 2, 0–15 min). The determination of 90 wt% LA was performed. com.The elution program was as follows: water / acetonitrile (98 / 2, 0–1 min), water / acetonitrile (20 / 80, 1–15 min), water / acetonitrile (20 / 80, 15–30 min), water / acetonitrile (98 / 2, 30–40 min). Figure 3 7.5 wt% as determined by high performance liquid chromatography Rac -LA chem. 90wt% Rac -LA com. 90wt% L -LA com. 90wt% D -LA com. Components.

[0098] 90 wt% of commercially available products were analyzed by high performance liquid chromatography. Rac -LA com. Component identification and quantitative analysis revealed that the lactic acid solution directly obtained from the carbohydrate 1,3-dihydroxyacetone via a chemical catalytic method contained only lactic acid monomers; while commercially available 90wt% lactic acid solutions... Rac -LA com. It contains lactic acid monomer (LA), dimer (L2A), trimer (L3A) and tetramer (L4A), of which LA accounts for 58.4%. DD / LL -L2A accounted for 16.5%, DL -L2A is 14.7%, L n A(n=3~4) is 10.4%. Commercially available 90wt% D -LA com. The proportion of LA in China is 57.6%. DD -L2A accounted for 31.0%. Commercially available 90wt% L -LA com. The proportion of LA in China is 57.7%. LL -L2A accounted for 31.1%.

[0099] Comparative Example 1

[0100] The preparation of lactide using a commercially available racemic lactic acid solution was carried out according to the method of Example 2, the difference from Example 1 being that: in step (1), 0.5 g of 90 wt% lactic acid solution was used. Rac -LA com. Replace with 6.0g 7.5wt%. Rac -LA com. , consisting of 90wt% Rac -LA com. The reaction can be carried out directly after simple dilution.

[0101] Depend on Figure 2 It can be seen that, through 1¹H NMR analysis yielded a stereoisomer selectivity of 1.41 for the product lactide. This example illustrates that after dilution, 7.5 wt% was obtained. Rac -LA com. Used in the preparation of lactide products, the stereoisomers of the products are still unevenly distributed. Meso The reduced stereoselectivity of -LD was not directly caused by the difference in apparent concentration, which also indicates that the water content and the ratio of organic solvents do not affect the stereoisomer distribution of the product.

[0102] Comparative Example 2

[0103] Following the method of Example 2, 90 wt% of commercially available optically active ingredients were used. D -LA com. and 90wt% L -LA com. 90wt% of the configured racemic DL -LA com. The solution preparation of lactide differs from that in Example 2 in that: in step (1), 90 wt% Rac -LA com. Replace with 90wt% DL -LA com. .

[0104] 90 wt% of commercially available products were analyzed by high performance liquid chromatography. DL -LA com. Quantitative analysis was performed. LA accounted for 57.6% of the total. DD -L2A accounted for 15.5%, LL -L2A accounted for 15.6%, DL -L2A is 0.0%, L n A(n=3-4) is 11.3%. (Passed) 1 ¹H NMR analysis showed a lactic acid conversion rate of 95% and a lactide yield of 47%, with a stereoisomer selectivity of 2.81 for the lactide product. This example illustrates the uneven stereoisomer distribution in the lactide product, even in the absence of lactide. DL -L2A system products Meso - The stereoselectivity of LD is further reduced.

[0105] Comparative Example 3

[0106] Following the method of Example 2, 90 wt% of a commercially available racemic lactic acid solution was used. Rac -LA com. and the configured racemic 90wt% DL The preparation of lactide using LA solution differs from Example 2 in that:

[0107] 90wt% Rac-LA com. Replace with 90wt% DL -LA com. and 90wt% Rac -LA com. The mixed solutions were mixed in the following ratios (w:w): (0:1), (1:3), (1:1), (3:1), and (1:0).

[0108] Figure 4 Stereoisomer distribution diagram of lactide prepared from racemic lactic acid solutions with different dimer contents for Comparative Example 3.

[0109] Depend on Figure 4 It can be seen that the stereoisomer selectivity of lactide products corresponding to the mixing ratios (w:w) of (0:1), (1:3), (1:1), (3:1), and (1:0) are 1.61, 1.84, 2.13, 2.44, and 2.81, respectively. This indicates that lactic acid dimers can enter the H-Beta molecular sieve channels as intermediates to complete cyclization, meaning that lactide products can be obtained not only from lactic acid monomers but also from lactic acid dimers initially present in the system. Furthermore, when the system is pretreated (at a pretreatment temperature of 80℃) to reduce the lactic acid content of lactide products... DD -L2A or LL When the relative content of -L2A increased from 31.1% to 35.7%, the stereoisomer selectivity of the product lactide increased from 2.81 to 3.21. This further indicates that both lactic acid monomer and dimer are precursor forms of the product, and the stereodistribution of the product will be affected by the relative contents of the two precursors.

[0110] Comparative Example 4

[0111] Following the method of Example 2, 90 wt% of a commercially available racemic lactic acid solution was used. Rac -LA com. The solution preparation of lactide differs from Example 2 in that samples were taken from the reaction solution at different time points during the reaction, and after the same post-treatment, the solution was... 1 The products, lactide and lactic acid dimer, were identified and analyzed by ¹H NMR and HPLC.

[0112] Figure 5 This illustrates the changes in components within the reaction system during Comparative Example 4. The stereoisomer ratio of lactide gradually decreases and approaches equilibrium with increasing reaction time. In the initial stage, some LD can be directly generated from L2A in the substrate, while the dimer portion has a higher proportion at this time. DL -L2A, the corresponding lactide product has less Meso -LD. Explanation DL -L2A inlet channel relative to DD / LL -L2A is restricted, therefore reducingMeso -LD exhibits stereoselectivity, with lactide products showing a stereoisomer ratio reaching 2.0. This varies depending on the initial substrate composition. DD / LL The continued consumption of -L2A and the increase in products obtained from lactic acid monomers, by X -L2A gradually weakens the significance of the stereoisomerism difference in the products, making D / L- LD and Meso The distributional differences of -LD weaken. Correspondingly, DL -L2A accumulates over a certain period, leading to an increase in its relative content, and then tends to stabilize in the later stages of the reaction. During the reaction, the dynamic changes in substrate and product indicate that when lactic acid dimers exist outside the pores in the system, the stereoisomerization of lactide is related to the stereoisomerization of the dimer. H-Beta molecular sieve catalysts... X -L2A exhibits a certain degree of stereoselectivity, resulting in differences in the distribution of stereoisomers in the products.

[0113] Comparative Example 5

[0114] Lactose was prepared from racemic lactic acid solutions containing different dimer contents according to the method of Example 1, the difference being that in step (1), 7.5 wt% Rac -LA chem. Replace with X% Rac -LA com. and with regard to X -L2A exhibits the most pronounced stereoselectivity during the first 10 minutes of the reaction phase, exploring the relationship between stereoselectivity and dimerization. The X% Rac -LA com. middle X The contents of -L2A were 19.7%, 26.1%, 31.2%, 36.1%, and 29.2%, respectively, expressed as... X -L2A / (LA+ X The percentages of -L2A were 21.3%, 28.7%, 34.6%, 43.0%, and 58.9%, respectively.

[0115] Figure 6 Comparative Example 5 contains different X A graph showing the relationship between the stereoisomer ratio and dimer content when using a racemic lactic acid solution with an L2A distribution for lactide preparation. It can be seen that in the preferred solution containing X% L2A, through... 1 ¹H NMR analysis showed that the stereoisomer selectivity of the product lactide increased with increasing relative lactate dimer content, ranging from 1.26 to 2.79. This example illustrates that... Meso The stereoselectivity of -LD stems from the H-Beta molecular sieve's effect on the outer pores. X -L2A stereoselectivity.

[0116] Application Example 1

[0117] 0.5g 90wt% Rac -LA com. After mixing with 0.25g H-Beta molecular sieve, the mixture was stirred evenly at room temperature, and 5mL of organic solvent was added. The mixture was then placed in a preheated oil bath. The difference between this application example and Example 2 is that the organic solvent was replaced with o-xylene or mesitylene, and the reaction temperature was changed accordingly to 160℃ or 180℃, respectively.

[0118] Figure 7 The diagram shows the proportion of stereoisomers of lactide products obtained at different temperatures using different racemic lactic acid solutions from Examples 1-3.

[0119] Depend on Figure 7 Combination 1 ¹H NMR analysis calculated that the conversion rate of lactic acid in Application Example 1 was 97% (reaction temperature 160℃) or 100%, corresponding to a lactide yield of 46% or 25%, and the stereoisomer selectivity of the lactide product was 2.36 or 3.60. This example illustrates that the present invention utilizes H-Beta molecular sieves for... X The stereoselectivity of -L2A is accelerated in the initial stage by increasing the reaction temperature. X The formation rate of -L2A is reduced, thus leading to the formation of more L2A outside the molecular sieve channels. X -L2A amplifies the stereoselectivity effect. This invention, based on the same reaction substrate, achieves differences in the distribution of stereoisomers in the product through a simple temperature control strategy, reducing... Meso - Stereoselectivity of LD.

[0120] Application Example 2

[0121] Lactide was prepared using the stereoselectivity of H-Beta molecular sieves under the reaction conditions of Application Example 1, the difference being that: 90 wt% Rac -LA com. Replace with 90wt% DL -LA com. .

[0122] Depend on Figure 7 Combination 1 ¹H NMR analysis calculated that the conversion rate of lactic acid in Application Example 2 was 97% or 90%, the yield of lactide was 47% or 22%, and the stereoisomer selectivity of the product lactide was 2.81 or 3.74. This invention utilizes a temperature strategy to control the formation rate of lactic acid dimers outside the pores during the reaction, thereby achieving H-Beta molecular sieve-based... X The enhanced stereoselectivity of -L2A is universally applicable to different racemic lactic acid solutions.

[0123] Application Example 3

[0124] Lactide was prepared using the stereoselectivity of H-Beta molecular sieves under the reaction conditions of Application Example 1, the difference being that: 90 wt% Rac -LA com. Replace with 7.5wt%. Rac -LA chem. .

[0125] Depend on Figure 7 Combination 1 H₂ liquid NMR analysis calculated that the conversion rate of lactic acid in Application Example 3 was 77% or 95%, the yield of lactide was 25% or 36%, and the stereoisomer selectivity of the lactide product was 2.27 or 2.67. The temperature strategy of the present invention is universally applicable to improving the stereoselective distribution of lactide products obtained from racemic lactic acid solutions, and is not limited by the concentration of the initial components of the system or whether they are in dimer form.

[0126] Application Example 4

[0127] Lactide was prepared using the stereoselectivity of H-ZSM-5 molecular sieve according to the reaction conditions of Example 2, except that the H-Beta molecular sieve with twelve-membered ring channels (pore diameter: 0.67-0.75 nm) was replaced with the H-ZSM-5 molecular sieve with ten-membered ring channels (pore diameter: 0.51-0.56 nm).

[0128] pass 1 1H NMR analysis showed that the substrate was 90 wt% Rac -LA com. and 90wt% DL -LA com. The calculated yields of lactide were 14% and 18%, respectively, with stereoisomer selectivity of 1.93 and 6.7. This indicates that H-ZSM-5, due to its smaller pore size compared to H-Beta molecular sieves, can further utilize its shape selectivity to reduce the content of lactide in the product. Meso The selectivity of -LD is improved, but the yield of lactide obtained is significantly reduced, indicating that H-ZSM-5 is not an advantageous catalyst for the cyclization reaction of lactic acid monomers and dimers within the pores. However, it shows that adjusting the microporous structure of the catalyst is a promising method to reduce the formation of meso products.

[0129] Application Example 5

[0130] Following the reaction conditions of Application Example 1, lactide was stereoselectively prepared using H-Beat-R molecular sieves treated with the structure reconstruction method. The difference from Application Example 1 was that the commercial H-Beta molecular sieve was replaced with H-Beat-R molecular sieve, and 5 mL of toluene or o-xylene was added as organic solvent, with corresponding reaction temperatures of 140°C and 160°C, respectively.

[0131] The preparation method of H-Beat-R molecular sieve is as follows:

[0132] (1) H-Beta molecular sieve was added to tetraethylammonium hydroxide aqueous solution and subjected to first hydrothermal treatment at 70℃ to remove part of the water to obtain a mixture. The molar ratio of the mixture was: 1.0SiO2:0.04Al2O3:0.5TEAOH:7.5H2O;

[0133] (2) The mixture was transferred to a polytetrafluoroethylene-lined reactor for a second hydrothermal treatment at a temperature of 140°C for 45 min. This static hydrothermal treatment yielded a mixture in which the crystalline Beta phase was dissolved.

[0134] (3) Add ammonium fluoride (NH4F) to the mixture in which the above crystalline phase is dissolved, with a molar ratio of 1.0SiO2:0.04Al2O3:0.5TEAOH:7.5H2O:0.5NH4F, and perform a third hydrothermal treatment at a temperature of 140℃ for 24h. Static hydrothermal treatment is performed to obtain a recrystallized H-Beta phase gel.

[0135] (4) After centrifuging, washing and drying the gel phase, it is calcined in an air atmosphere. The heating program is 1℃ / min. The first calcination temperature is 200℃ and the time is 2h. The second calcination temperature is 550℃ and the time is 6h. The H-Beta after structural reconstruction is obtained and is denoted as H-Beta-R.

[0136] Figure 8 This is a comparison of XRD patterns between the H-Beta-R molecular sieve reconstructed using Example 5 and a commercial H-Beta molecular sieve. Figure 8 It can be seen that both H-Beta and H-Beta-R exhibit characteristic diffraction peaks at 2θ values ​​between 22.2° and 22.4° in the figure, indicating that the crystal structure of the molecular sieve is well preserved before and after treatment, and the molecular sieve has recrystallized after alkali dissolution. The silicon-to-aluminum ratio (Si / Al) obtained by ICP testing did not change significantly before and after treatment; the Si / Al ratio of H-Beta was 9.3, while that of H-Beta-R was 9.2, indicating that there was no loss of aluminum atoms during the molecular sieve treatment process.

[0137] Figure 9This is a comparison of the pyridine-infrared (PY-IR) spectra of the H-Beta-R molecular sieve reconstructed using Example 5 and the commercial H-Beta molecular sieve. The figure shows... The slight increase in the acid ratio from 1.63 to 1.89 also supports the conclusion that the molecular sieves were regularized, which is more conducive to differentiation. X -L2A enhances the stereoselectivity of lactide products.

[0138] Figure 10 The distribution of stereoisomers at different reaction times at 140°C during the application of the reconstructed H-Beta-R molecular sieve from Example 5 in the preparation of lactide was investigated. 1 H-liquid NMR analysis yielded lactic acid conversions of 92% and 98% at reaction temperatures of 140℃ and 160℃, respectively, along with lactide yields of 33% and 32%, and stereoisomer selectivity of 2.01 and 3.24 for the product lactide, respectively. In the initial stages (10 min and 30 min of reaction), where the stereoselectivity for lactic acid dimers was most pronounced, the regularization of the H-Beta molecular sieve further enhanced the stereoselectivity advantage. Figure 10 It is evident that H-Beta-R molecular sieves exhibit lower mesolacide selectivity in the initial stage of lactide cyclization, which can, to some extent, further prevent the formation of meso products. While the proportion of stereoisomers decreases with increasing monomer activity, it still relatively decreases compared to H-Beta. Meso The selectivity of -LD is more conducive to the practical application of racemic lactic acid and the preparation of various PLA products with the required microstructure.

[0139] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. Use of a molecular sieve in catalyzing stereoselective preparation of racemic lactide from racemic lactic acid, wherein the molecular sieve is a H-Beta molecular sieve; The application also includes: the H-Beta molecular sieve is subjected to a regularizing treatment before the catalyzing, and the regularizing treatment comprises the following steps: (a) mixing the H-Beta molecular sieve with an aqueous solution of tetraethylammonium hydroxide to perform a first hydrothermal treatment, to obtain a crystalline Beta phase dissolved mixture; (b) mixing the crystalline Beta phase dissolved mixture with ammonium fluoride to perform a second hydrothermal treatment, to obtain a re-crystallized H-Beta phase gel; (c) sequentially performing washing, drying and calcination on the H-Beta phase gel, to obtain the regularized H-Beta molecular sieve.

2. Use according to claim 1, characterized in that, the mixture obtained in the step (a) satisfies the molar ratio of SiO2:Al2O3:TEAOH:H2O = 1.0:0.04:0.5:7.5, and the mixture obtained in the step (b) satisfies the molar ratio of SiO2:Al2O3:TEAOH:H2O:NH4F = 1.0:0.04:0.5:7.5:0.5, in terms of SiO2 and Al2O3.

3. Use according to claim 1, characterized in that, the first hydrothermal treatment is performed at a temperature of 140℃ for 45 min, and the second hydrothermal treatment is performed at a temperature of 140℃ for 24 h; the calcination comprises sequentially performing a first calcination and a second calcination, the first calcination is performed at a temperature of 200℃ for 2 h, and the second calcination is performed at a temperature of 550℃ for 6 h.

4. A method for the stereoselective production of racemic propiolactone from racemic lactic acid, characterized in that, comprises the following steps: mixing a solution of racemic lactic acid, a molecular sieve catalyst and an organic solvent to perform an esterification reaction, to obtain a mixture of different configurations of lactide, wherein the mixture of different configurations of lactide comprises racemic lactide; the molecular sieve catalyst is the molecular sieve used in the use according to any one of claims 1-3.

5. The method of claim 4, wherein, the lactic acid in the solution of racemic lactic acid comprises lactic acid monomers and lactic acid dimers, and the content of the lactic acid monomers and the lactic acid dimers in the solution of racemic lactic acid is 13.2-100% and 0-36.1%, respectively.

6. The method according to claim 4 or 5, characterized in that, the mass ratio of the lactic acid in the solution of racemic lactic acid to the molecular sieve catalyst is 0.9-9:

1.

7. The method of claim 4, wherein, the organic solvent is toluene, o-xylene or mesitylene.

8. The method according to claim 4 or 7, characterized in that, the esterification reaction is performed at a temperature of 140-180℃ for 10 min-3 h.

9. The method of claim 8, wherein, the esterification reaction is performed at a temperature of 160-180℃.

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