CN109337052B - Method for producing poly-L-lactic acid by ring-opening polymerization of L-lactide - Google Patents
Method for producing poly-L-lactic acid by ring-opening polymerization of L-lactide Download PDFInfo
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Abstract
The invention discloses a method for producing poly-L-lactic acid by ring-opening polymerization of L-lactide, which comprises the steps of adding L-lactide into a poly-L-lactic acid reaction kettle, wherein the adding amount of a catalyst is 0.04-0.5% of the mass of the L-lactide, the reaction temperature is 140-170 ℃, the reaction time is 10-50h, and the reaction pressure is less than or equal to 10 pa. The present invention provides a method for preparing poly-L-lactic acid using L-lactide, and also provides a method for producing L-lactic acid oligomer from L-lactic acid monomer and preparing L-lactide therefrom, thereby industrially realizing a complete process for preparing poly-L-lactic acid from L-lactic acid monomer.
Description
Technical Field
The invention relates to the technical field of lactic acid deep processing. More particularly, it relates to a method for producing poly-L-lactic acid by using ring-opening polymerization of L-lactide.
Background
The poly-L-lactic acid is a polymer with excellent performance, biocompatibility and biodegradability, and is mainly used in the aspects of degradable packaging materials, drug microsphere carriers, anti-adhesion films, biological catheters, orthopedic fixtures, orthopedic surgery devices, artificial bones and other medical materials.
In the process of preparing the poly-L-lactic acid by the monomer lactic acid, firstly, the monomer lactic acid generates a lactic acid oligomer, and then the lactic acid oligomer is directly condensed to prepare the poly-L-lactic acid, or the lactic acid oligomer is used for preparing the L-lactide, and then the L-lactide is subjected to ring-opening polymerization to generate the poly-L-lactic acid.
The low-poly L-lactic acid is not only used as a raw material for preparing poly L-lactic acid but also as a pharmaceutical intermediate, and chinese patent document CN1498237A discloses a method for preparing a lactic acid oligomer, which uses lactide as a raw material to selectively prepare a mixture of linear and cyclic lactic acid oligomers. The disadvantages of this method are: (1) lactide is required to be used as a raw material, but in industrial production, lactic acid monomers are used as the most cheap raw materials, the cost for directly preparing the lactide from the lactic acid monomers is high, and only the byproduct lactide in melt polycondensation can be used as the raw material; (2) the used solvents such as tetrahydrofuran are toxic and are not suitable for industrial application.
In large-scale industrial production, it is difficult to directly obtain high-purity L-lactide from a monomer L-lactic acid; in the process of producing poly-L-lactic acid by melt polycondensation and solid phase polycondensation, the lactide in industrial production is usually the byproduct crude L-lactide generated in the melt polycondensation process, and the crude L-lactide can be subjected to ring-opening polymerization to produce high molecular weight poly-L-lactic acid after being purified.
Disclosure of Invention
An object of the present invention is to provide a method for preparing poly L-lactic acid using L-lactide, and also to provide a method for producing L-lactic acid oligomers from L-lactic acid monomers and preparing L-lactide therefrom, thereby industrially realizing a complete process for preparing poly L-lactic acid from L-lactic acid monomers.
In order to achieve the purpose, the invention adopts the following technical scheme: the method for producing poly-L-lactic acid by utilizing the ring-opening polymerization of L-lactide comprises the steps of adding the L-lactide into a poly-L-lactic acid reaction kettle, wherein the adding amount of a catalyst is 0.04-0.5 percent of the mass of the L-lactide, the reaction temperature is 140-170 ℃, the reaction time is 10-50h, and the reaction pressure is less than or equal to 10 pa.
In the method for producing the poly-L-lactic acid by utilizing the ring-opening polymerization of the L-lactide, the catalyst is a mixture of zirconium oxide and molybdenum glycinate according to the ratio of 1.5-2.5: 1.
In the method for producing poly L-lactic acid by ring-opening polymerization of L-lactide, the preparation method of molybdenum glycinate is as follows: mixing and stirring sodium molybdate and glycine hydroxy acid in a methanol solution at room temperature, and reacting for 2-3h to obtain solid molybdenum glycine hydroxy acid; the quantity ratio of the cysteine methyl ester to the sodium molybdate substances is 4:1, and the concentration of the sodium molybdate in the methanol solution is 0.1-2 mol/L.
According to the method for producing the poly-L-lactic acid by utilizing the ring-opening polymerization of the L-lactide, the adding amount of the catalyst is 0.1 percent of the mass of the L-lactide, the reaction temperature is 160 ℃, and the reaction time is 20 hours.
In the method for producing poly L-lactic acid by utilizing the ring-opening polymerization of L-lactide, the preparation method of the L-lactide comprises the following steps:
(1) preparing raw materials: 40-60 wt% of L-lactic acid solution, the optical purity of the L-lactic acid is more than or equal to 99.5%;
(2) dehydrating and oligomerizing to obtain L-lactic acid oligomer;
(3) and depolymerizing the L-lactic acid oligomer to prepare L-lactide.
In the method for producing poly L-lactic acid by utilizing the ring-opening polymerization of L-lactide, in the step (2), ethyl pyruvate is added into the L-lactic acid solution, and the volume ratio of the ethyl pyruvate to the L-lactic acid solution is 0.5-1: 1; simultaneously adding cobalt oxide and di-cysteine methyl ester vanadyl as catalysts into the mixed solution, and stirring; the usage amount of the cobalt oxide is 0.02-0.04 percent of the mass of the L-lactic acid, and the usage amount of the di-cysteine methyl ester vanadyl is 0.04-0.08 percent of the mass of the L-lactic acid; the reaction time is 3-6 h, and the reaction temperature is 5-30 ℃.
The method for producing poly-L-lactic acid by ring-opening polymerization of L-lactide comprises the following steps (2):
initial reaction: the mass ratio of the added cobalt oxide to the added di-cysteine methyl ester vanadyl is 1:1.5, and the addition amount of the cobalt oxide in the initial reaction is 1/2 of the total addition amount of the cobalt oxide; the reaction temperature is kept between 5 and 10 ℃ from the initial reaction to the time when one half of the reaction time is passed;
when the reaction time is one-half elapsed: adding all the residual di-cysteine methyl ester vanadyl into a reaction kettle; the reaction temperature is kept between 15 and 20 ℃ from one half of the reaction time to three quarters of the reaction time;
three quarters of the time elapsed: adding the rest cobalt oxide into the reaction kettle; the reaction temperature is kept between 25 and 30 ℃ from the end of the reaction to the end of the reaction after three quarters of the reaction time.
In the method for producing poly-L-lactic acid by ring-opening polymerization of L-lactide, in the step (2), the preparation method of di-cysteine methyl ester vanadyl comprises the following steps: mixing and stirring cysteine methyl ester and vanadyl sulfate in boric acid solution at room temperature, and reacting for 3-5h to obtain purple solid; the amount ratio of the cysteine methyl ester to the vanadyl sulfate substance is 5:1, and the concentration of the cysteine methyl ester in the boric acid solution is 0.1-5 mol/L.
In the method for producing poly-L-lactic acid by utilizing the ring-opening polymerization of L-lactide, in the step (2), after the reaction is finished, the filtration, the standing and the layering are carried out, an organic phase is separated out, and the organic phase is washed by water; and (4) carrying out vacuum distillation on the organic phase after washing by water to remove the solvent, thus obtaining a white solid.
In the step (3), the L-lactic acid oligomer obtained in the step (2) is put into a lactide preparation kettle, the temperature is raised to 145-160 ℃, and the L-lactic acid oligomer is melted; the catalyst used for synthesizing the L-lactide is a mixture of nickel oxide and molybdenum glycinate, the usage amount of the nickel oxide is 0.01 to 0.03 percent of the mass of the L-lactic acid oligomer, the usage amount of the molybdenum glycinate is 0.03 to 0.09 percent of the mass of the L-lactic acid oligomer, the reaction time is 3 to 5 hours, and the reaction pressure is 0.01 multiplied by 105Pa-0.1×105Pa；
Initial reaction: the mass ratio of the added nickel oxide to the added molybdenum glycinate is 1:2, and the addition amount of the nickel oxide during the initial reaction is 1/3 of the total addition amount of the nickel oxide;
when one third of the reaction time has elapsed: adding the rest nickel oxide into the lactide preparation kettle;
two thirds of the reaction time elapsed: adding the rest molybdenum glycinate into the lactide preparation kettle;
the preparation method of molybdenum glycinate comprises the following steps: mixing and stirring sodium molybdate and glycine hydroxy acid in a methanol solution at room temperature, and reacting for 2-3h to obtain solid molybdenum glycine hydroxy acid; the quantity ratio of glycine hydroxy acid to sodium molybdate is 4:1, and the concentration of sodium molybdate in the methanol solution is 0.1-2 mol/L;
the upper part of the lactide preparation kettle is communicated with the fluid of the condensation collection tank through a heat insulation pipeline, and the generated L-lactide is cooled and crystallized in the condensation collection tank.
The invention has the following beneficial effects:
(1) the method takes the cheap and easily obtained L-lactic acid monomer in the actual industrial production as the raw material, is worth of the L-lactic acid oligomer with narrower molecular weight distribution, has mild reaction condition, easy control and high L-lactic acid oligomer yield, and is suitable for industrial production.
(2) The lactide is prepared by taking the L-lactic acid oligomer as a raw material, the yield and the purity of the L-lactide are high, the reaction pressure is improved, and energy is saved in industrial production.
(3) The complete process flow of preparing poly L-lactic acid from L-lactic acid monomer is realized industrially.
Drawings
FIG. 1 shows the effect of the amount of catalyst on the L-lactide ring-opening polymerization product on the abscissa of the amount of catalyst in wt% and the ordinate of the weight-average molecular weight M of poly D-lactic acidW×105)；
FIG. 2 shows the effect of the reaction temperature on the molecular weight of the product of the ring-opening polymerization of L-lactide (the abscissa represents the reaction temperature, and the ordinate represents the weight-average molecular weight M of poly-D-lactic acidW×105)；
FIG. 3 shows the effect of polymerization time on the molecular weight of the product of ring-opening polymerization of L-lactide (reaction time h on the abscissa and weight-average molecular weight M of poly-D-lactic acid on the ordinate)W×105)。
Detailed Description
In order to more clearly illustrate the invention, the invention is further described below with reference to preferred embodiments and the accompanying drawings. Similar parts in the figures are denoted by the same reference numerals. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and is not to be taken as limiting the scope of the invention.
First part of the research on the production of poly-L-lactic acid by ring-opening polymerization of L-lactide
The production of the poly-L-lactic acid can adopt a method of melt polycondensation and solid phase polycondensation to generate the poly-L-lactic acid with higher molecular weight, and can also utilize L-lactide ring-opening polymerization to produce the poly-L-lactic acid with higher molecular weight. In the process of producing poly-L-lactic acid by melt polycondensation and solid phase polycondensation, a byproduct, namely crude L-lactide, is generated in the melt polycondensation process, but the crude L-lactide needs to be purified and then can be subjected to ring opening polymerization to produce high molecular weight poly-L-lactic acid. The raw material L-lactide used in the present invention is L-lactide produced by L-lactic acid (see example 1 in the second section in particular), but is also suitable for producing poly L-lactic acid by purifying crude L-lactide, which is a by-product of a melt polycondensation process, as a raw material.
1. Effect of the amount of catalyst (mixture of zirconium oxide and molybdenum Glycine carboxylate in a 2:1 ratio as catalyst) on the molecular weight of Poly-L-lactic acid produced by Ring opening polymerization of L-lactide
Under the conditions of reaction pressure less than or equal to 10pa and the same conditions of reaction time, reaction temperature and the like, the influence of different catalyst dosages on the molecular weight of the poly-L-lactic acid is tested, and the result is shown in figure 1.
As can be seen from FIG. 1, as the amount of the catalyst (percentage of the mass of L-lactide) increases, the molecular weight of the product poly-L-lactic acid increases and then decreases, because the amount of the catalyst increases, the number of coordination sites with L-lactide increases, and the molecular weight of the poly-L-lactic acid decreases. And comprehensively considering the generation efficiency, selecting three indexes of 0.08 percent, 0.1 percent and 0.12 percent of catalyst dosage, and carrying out orthogonal test by combining the reaction time and the reaction temperature.
2. Influence of polymerization reaction temperature on molecular weight of poly-L-lactic acid product
The effect of different reaction temperatures on the weight-average molecular weight of the poly L-lactic acid was examined under the same conditions of reaction pressure of 10Pa or less, reaction time, amount of catalyst added (a mixture of zirconium oxide and molybdenum glycinate in a ratio of 2:1 as catalyst), etc., and the results are shown in FIG. 2.
As can be seen from FIG. 2, the mass of the poly L-lactic acid molecule increases first and then decreases with the increase of the reaction temperature, because when the reaction temperature is too high, the thermal degradation speed of the polymer is accelerated, and any part of the macromolecular chain is broken, resulting in the decrease of the molecular weight of the poly L-lactic acid. Comprehensively considering, the orthogonal test is carried out by selecting 155 ℃, 160 ℃ and 165 ℃, and the addition amount and reaction time of the catalyst.
3. Effect of polymerization time on the molecular weight of the product Poly-L-lactic acid
The effect of different reaction times on the molecular weight of poly-L-lactic acid was tested under the same conditions at a reaction pressure of 10Pa or less, and the results are shown in FIG. 3.
As can be seen from FIG. 3, the molecular weight of poly-L-lactic acid increases and then gradually decreases as the polymerization time increases. This is because the molecular weight of poly-L-lactic acid increases with time, and after reaching a certain value, the number of L-lactides in the reaction system decreases, which leads to a predominant depolymerization reaction, and a part of high molecular weight linear poly-L-lactic acid molecules are broken, resulting in a decrease in the molecular weight of poly-L-lactic acid. In order to determine the optimal process and the comprehensive production efficiency, 15h, 20h and 25h are selected for orthogonal tests.
Combined design of L-lactide ring-opening polymerization process index
The reaction pressure is less than or equal to 10pa as a control constant, the addition amount of a catalyst (a mixture of zirconium oxide and molybdenum glycinate in a ratio of 2:1 is used as the catalyst), the reaction time and the reaction temperature are independent variables, and the weight average molecular weight M of the product poly L-lactic acidWAnalysis was performed for dependent variables.
Test results and significance test thereof
In the experiment, three main factors influencing the ring-opening polymerization process of the L-lactide are determined, three levels of the three factors are determined through a large number of experiments, 3 levels of the three factors are designed according to the center combination design principle of Box-Behnken, and the experiment results are shown in table 1 and table 2.
TABLE 1 three-factor three-level table
TABLE 2 Box-Behnken test results
Regression fitting was performed on the test data in table 2 by stepwise regression using Design expert statistical software, and analysis of variance and significance tests were performed. It is determined that the influence of each influencing factor on the molecular weight of the product poly-L-lactic acid is not a simple linear relationship. According to a response surface diagram and contour line analysis, determining the optimal point of the three factors, selecting the starting point in the range of the model, optimizing by using a rapid rise method according to the model, and finally obtaining the maximum poly-L-lactic acid molecular weight when determining that the molecular weight is A0.1%, B160 ℃ and C20 h.
In order to test the reliability of the Box-Behnken experiment design result, an optimized proportioning experiment is adopted, and the test result is shown in Table 3.
TABLE 3L-lactide Ring-opening polymerization test results
The average molecular weight of the finally extracted poly L-lactic acid was found to be 1.53X 105The technological parameters of catalyst addition, reaction time and reaction temperature obtained by Box-Behnken test design are accurate and reliable, have practical value and are the optimal technological parameters. The optimized process for producing the poly-L-lactic acid by the ring-opening polymerization of the L-lactide is obtained through the experiments: namely, the reaction pressure is less than or equal to 10Pa, the adding amount of a catalyst (a mixture of zirconium oxide and molybdenum glycinate according to the ratio of 2:1 is used as the catalyst) accounts for 0.1 percent of the mass of the L-lactide, the reaction time is 20h, and the reaction temperature is 160 ℃.
Second part of the process for producing L-lactide, which is a raw material used in the present invention
Example 1
A method for producing L-lactide by using L-lactic acid, comprising the steps of:
(1) preparing raw materials: the optical purity of the L-lactic acid produced by the applicant is greater than or equal to 99.5% in a 45 wt% L-lactic acid solution;
(2) dehydrating and oligomerizing to obtain L-lactic acid oligomer;
adding ethyl pyruvate into the L-lactic acid solution, and stirring to obtain a mixed solution, wherein the volume ratio of the ethyl pyruvate to the L-lactic acid solution is 1: 1;
simultaneously, cobalt oxide and di-cysteine methyl ester vanadyl are added into the mixed solution as catalysts according to the following steps:
initial reaction (0 h): the mass ratio of the added cobalt oxide to the added di-cysteine methyl ester vanadyl is 1:1.5, and the addition amount of the cobalt oxide in the initial reaction is 1/2 of the total addition amount of the cobalt oxide; the reaction temperature was kept at 5 ℃ from the initial reaction to the time when one-half of the reaction time elapsed; stirring;
when the reaction time is one half (2 h): adding all the residual di-cysteine methyl ester vanadyl into a reaction kettle; the reaction temperature is kept at 15 ℃ from one half of the reaction time to three quarters of the reaction time; stirring;
three quarters of the reaction time had elapsed (3 h): adding the rest cobalt oxide into the reaction kettle; the reaction temperature is kept at 25 ℃ from three quarters of the reaction time to the end of the reaction; and (4) stirring.
The usage amount of the cobalt oxide is 0.02 percent of the mass of the L-lactic acid, and the usage amount of the di-cysteine methyl ester vanadyl is 0.04 percent of the mass of the L-lactic acid; the preparation method of di-cysteine methyl ester vanadyl comprises the following steps: mixing and stirring cysteine methyl ester and vanadyl sulfate in boric acid solution at room temperature, and reacting for 3-5h to obtain purple solid; the quantity ratio of the cysteine methyl ester to the vanadyl sulfate substance is 5:1, and the concentration of the cysteine methyl ester in the boric acid solution is 2 mol/L.
After the reaction is finished, filtering, standing for layering, separating out an organic phase, and washing the organic phase with water; and (3) carrying out vacuum distillation on the organic phase after washing with water to remove the solvent, thus obtaining a white solid, and carrying out fast atom bombardment mass spectrum and nuclear magnetic detection on the obtained white solid, wherein the white solid is the L-lactic acid oligomer of the 6-19 polymer, and the yield of the L-lactic acid oligomer is 95%.
(3) Depolymerizing the L-lactic acid oligomer to prepare L-lactide;
putting the L-lactic acid oligomer obtained in the step (2) into a lactide preparation kettle, and conducting the upper part of the lactide preparation kettle with a fluid of a condensation collection tank through a heat insulation pipeline; heating the lactide preparation kettle to 145 ℃ to melt the L-lactic acid oligomer;
the mixture of nickel oxide and molybdenum glycinate was added as a catalyst to the lactide preparation kettle according to the following procedure (nickel oxide used in an amount of 0.01% by mass of the L-lactic acid oligomer, molybdenum glycinate used in an amount of 0.03% by mass of the L-lactic acid oligomer, reaction time of 3h, reaction pressure of 0.01X 105Pa)：
Initial reaction (0 h): the mass ratio of the added nickel oxide to the added molybdenum glycinate is 1:2, and the addition amount of the nickel oxide during the initial reaction is 1/3 of the total addition amount of the nickel oxide;
when one third of the reaction time has elapsed (1 h): adding the rest nickel oxide into the lactide preparation kettle;
when two thirds of the reaction time had elapsed (2 h): the remaining molybdenum glycinate was added to the lactide preparation kettle in its entirety.
The preparation method of molybdenum glycinate comprises the following steps: mixing and stirring sodium molybdate and glycine hydroxy acid in a methanol solution at room temperature, and reacting for 3 hours to obtain solid molybdenum glycine hydroxy acid; the weight ratio of glycine hydroxy acid to sodium molybdate is 4:1, and the concentration of sodium molybdate in the methanol solution is 2 mol/L.
The generated L-lactide is cooled and crystallized in a condensation collection tank, the yield of the L-lactide is 98.5 percent, and the optical purity is 99.9 percent.
Example 2
A method for producing L-lactide by using L-lactic acid, comprising the steps of:
(1) preparing raw materials: the optical purity of the L-lactic acid produced by the applicant is greater than or equal to 99.5% in a 60 wt% L-lactic acid solution;
(2) dehydrating and oligomerizing to obtain L-lactic acid oligomer;
adding ethyl pyruvate into the L-lactic acid solution, and stirring to obtain a mixed solution, wherein the volume ratio of the ethyl pyruvate to the L-lactic acid solution is 1: 1; adding cobalt oxide and di-cysteine methyl ester vanadyl as catalysts into the mixed solution; the using amount of the cobalt oxide is 0.04 percent of the mass of the L-lactic acid, the using amount of the di-cysteine methyl ester vanadyl is 0.08 percent of the mass of the L-lactic acid, and the mixture is stirred and reacted for 3 hours at room temperature; the preparation method of di-cysteine methyl ester vanadyl comprises the following steps: mixing and stirring cysteine methyl ester and vanadyl sulfate in boric acid solution at room temperature, and reacting for 3-5h to obtain purple solid; the quantity ratio of the cysteine methyl ester to the vanadyl sulfate substance is 5:1, and the concentration of the cysteine methyl ester in the boric acid solution is 0.5 mol/L.
After the reaction is finished, filtering, standing for layering, separating out an organic phase, and washing the organic phase with water; carrying out vacuum distillation on the organic phase after washing with water to remove the solvent, thus obtaining a white solid, and carrying out fast atom bombardment mass spectrum and nuclear magnetic detection on the obtained white solid, wherein the white solid contains L-lactic acid oligomer of 6-19 polymers and L-lactic acid oligomer of 30-50 polymers; the yield of L-lactic acid oligomer was 82%.
(3) Depolymerizing the L-lactic acid oligomer to prepare L-lactide;
putting the L-lactic acid oligomer obtained in the step (2) into a lactide preparation kettle, and conducting the upper part of the lactide preparation kettle with a fluid of a condensation collection tank through a heat insulation pipeline; heating the lactide preparation kettle to 150 ℃ to melt the L-lactic acid oligomer; a mixture of nickel oxide and molybdenum glycinate carboxylate was added as catalyst to the lactide preparation kettle:
initial reaction (0 h): the mass ratio of the added nickel oxide to the added molybdenum glycinate is 1:2, and the addition amount of the nickel oxide during the initial reaction is 1/3 of the total addition amount of the nickel oxide;
when one third of the reaction time has elapsed (1 h): adding the rest molybdenum glycinate into the lactide preparation kettle;
three quarters of the reaction time had elapsed (2 h): adding the rest nickel oxide into the lactide preparation kettle.
The usage amount of nickel oxide is 0.03 percent of the quality of the L-lactic acid oligomer, the usage amount of molybdenum glycinate carboxylate is 0.09 percent of the quality of the L-lactic acid oligomer, the reaction time is 3 hours, and the reaction pressure is 0.1 multiplied by 105Pa; the preparation method of molybdenum glycinate comprises the following steps: mixing and stirring sodium molybdate and glycine hydroxy acid in a methanol solution at room temperature, and reacting for 3 hours to obtain solid molybdenum glycine hydroxy acid; the quantity ratio of glycine hydroxy acid and sodium molybdate substances is 4:1, and the concentration of sodium molybdate in the methanol solution is 1 mol/L.
The generated L-lactide is cooled and crystallized in a condensation collection tank, the yield of the L-lactide is 90.2 percent, and the optical purity is 99.9 percent.
Example 3
A method for producing L-lactide by using L-lactic acid, comprising the steps of:
(1) preparing raw materials: the optical purity of the L-lactic acid produced by the applicant is greater than or equal to 99.5% in a 50 wt% L-lactic acid solution;
(2) dehydrating and oligomerizing to obtain L-lactic acid oligomer;
adding ethyl pyruvate into the L-lactic acid solution, and stirring to obtain a mixed solution, wherein the volume ratio of the ethyl pyruvate to the L-lactic acid solution is 1: 1;
simultaneously, cobalt oxide and di-cysteine methyl ester vanadyl are added into the mixed solution as catalysts according to the following steps:
initial reaction (0 h): the mass ratio of the added cobalt oxide to the added di-cysteine methyl ester vanadyl is 1:1.5, and the addition amount of the cobalt oxide in the initial reaction is 1/2 of the total addition amount of the cobalt oxide; the reaction temperature was kept at 10 ℃ from the initial reaction to the time when one-half of the reaction time elapsed; stirring;
when the reaction time was one-half (3 h): adding the rest cobalt oxide into the reaction kettle; the reaction temperature is kept at 15 ℃ from one half of the reaction time to three quarters of the reaction time; stirring;
three quarters of the reaction time had elapsed (4.5 h): adding all the residual di-cysteine methyl ester vanadyl into a reaction kettle; the reaction temperature is kept at 30 ℃ from three quarters of the reaction time to the end of the reaction; and (4) stirring.
The usage amount of the cobalt oxide is 0.03 percent of the mass of the L-lactic acid, and the usage amount of the di-cysteine methyl ester vanadyl is 0.06 percent of the mass of the L-lactic acid; the preparation method of di-cysteine methyl ester vanadyl comprises the following steps: mixing and stirring cysteine methyl ester and vanadyl sulfate in boric acid solution at room temperature, and reacting for 3-5h to obtain purple solid; the quantity ratio of the cysteine methyl ester to the vanadyl sulfate substance is 5:1, and the concentration of the cysteine methyl ester in the boric acid solution is 1 mol/L.
After the reaction is finished, filtering, standing for layering, separating out an organic phase, and washing the organic phase with water; and (3) carrying out vacuum distillation on the organic phase after washing with water to remove the solvent, thus obtaining a white solid, and carrying out fast atom bombardment mass spectrum and nuclear magnetic detection on the obtained white solid, wherein the white solid is the L-lactic acid oligomer of the 6-40 polymer, and the yield of the L-lactic acid oligomer is 90%.
(3) Depolymerizing the L-lactic acid oligomer to prepare L-lactide;
putting the L-lactic acid oligomer obtained in the step (2) into a lactide preparation kettle, and conducting the upper part of the lactide preparation kettle with a fluid of a condensation collection tank through a heat insulation pipeline; heating the lactide preparation kettle to 160 ℃ to melt the L-lactic acid oligomer; adding a mixture of nickel oxide and molybdenum glycinate as a catalyst into a lactide preparation kettle; the usage amount of nickel oxide is 0.02 percent of the quality of the L-lactic acid oligomer, the usage amount of molybdenum glycinate carboxylate is 0.06 percent of the quality of the L-lactic acid oligomer, the reaction time is 5 hours, and the reaction pressure is 0.05 multiplied by 105Pa; the preparation method of molybdenum glycinate comprises the following steps: mixing and stirring sodium molybdate and glycine hydroxy acid in a methanol solution at room temperature, and reacting for 3 hours to obtain solid molybdenum glycine hydroxy acid; the quantity ratio of glycine hydroxy acid and sodium molybdate substances is 4:1, and the concentration of sodium molybdate in the methanol solution is 1 mol/L.
The generated L-lactide is cooled and crystallized in a condensation collection tank, the yield of the L-lactide is 78.3 percent, and the optical purity is 99.9 percent.
It should be understood that the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention, and it will be obvious to those skilled in the art that other variations or modifications may be made on the basis of the above description, and all embodiments may not be exhaustive, and all obvious variations or modifications may be included within the scope of the present invention.
Claims (6)
1. The method for producing the poly-L-lactic acid by utilizing the ring-opening polymerization of the L-lactide is characterized in that the L-lactide is added into a poly-L-lactic acid reaction kettle, the adding amount of a catalyst is 0.04 to 0.5 percent of the mass of the L-lactide, the reaction temperature is 140 to 170 ℃, the reaction time is 10 to 50 hours, and the reaction pressure is less than or equal to 10 pa;
the catalyst is a mixture of zirconium oxide and molybdenum glycinate according to the ratio of 1.5-2.5: 1;
the preparation method of molybdenum glycinate is as follows: mixing and stirring sodium molybdate and glycine hydroxy acid in a methanol solution at room temperature, and reacting for 2-3h to obtain solid molybdenum glycine hydroxy acid; the quantity ratio of the cysteine methyl ester to the sodium molybdate substances is 4:1, and the concentration of the sodium molybdate in the methanol solution is 0.1-2 mol/L;
the preparation method of the L-lactide comprises the following steps:
(1) preparing raw materials: 40-60 wt% of L-lactic acid solution, the optical purity of the L-lactic acid is more than or equal to 99.5%;
(2) dehydrating and oligomerizing to obtain L-lactic acid oligomer;
(3) depolymerizing the L-lactic acid oligomer to prepare L-lactide;
in the step (2), adding ethyl pyruvate into the L-lactic acid solution, wherein the volume ratio of the ethyl pyruvate to the L-lactic acid solution is 0.5-1: 1; simultaneously adding cobalt oxide and di-cysteine methyl ester vanadyl as catalysts into the mixed solution, and stirring; the usage amount of the cobalt oxide is 0.02-0.04 percent of the mass of the L-lactic acid, and the usage amount of the di-cysteine methyl ester vanadyl is 0.04-0.08 percent of the mass of the L-lactic acid; the reaction time is 3-6 h, and the reaction temperature is 5-30 ℃.
2. The method for producing poly-L-lactic acid by L-lactide ring-opening polymerization according to claim 1, wherein the amount of the catalyst added is 0.1% by mass of L-lactide, the reaction temperature is 160 ℃ and the reaction time is 20 hours.
3. The method for producing poly-L-lactic acid by L-lactide ring-opening polymerization according to claim 1, wherein in step (2):
initial reaction: the mass ratio of the added cobalt oxide to the added di-cysteine methyl ester vanadyl is 1:1.5, and the addition amount of the cobalt oxide in the initial reaction is 1/2 of the total addition amount of the cobalt oxide; the reaction temperature is kept between 5 and 10 ℃ from the initial reaction to the time when one half of the reaction time is passed;
when the reaction time is one-half elapsed: adding all the residual di-cysteine methyl ester vanadyl into a reaction kettle; the reaction temperature is kept between 15 and 20 ℃ from one half of the reaction time to three quarters of the reaction time;
three quarters of the time elapsed: adding the rest cobalt oxide into the reaction kettle; the reaction temperature is kept between 25 and 30 ℃ from the end of the reaction to the end of the reaction after three quarters of the reaction time.
4. The method for producing poly-L-lactic acid by L-lactide ring-opening polymerization according to claim 3, wherein the di-cysteine methyl ester vanadyl is prepared in step (2) by: mixing and stirring cysteine methyl ester and vanadyl sulfate in boric acid solution at room temperature, and reacting for 3-5h to obtain purple solid; the amount ratio of the cysteine methyl ester to the vanadyl sulfate substance is 5:1, and the concentration of the cysteine methyl ester in the boric acid solution is 0.1-5 mol/L.
5. The method for producing poly-L-lactic acid by ring-opening polymerization of L-lactide according to claim 4, wherein in step (2), after the reaction is completed, the reaction mixture is filtered, allowed to stand for delamination, the organic phase is separated, and the organic phase is washed with water; and (4) carrying out vacuum distillation on the organic phase after washing by water to remove the solvent, thus obtaining a white solid.
6. The method for producing poly-L-lactic acid by ring-opening polymerization of L-lactide according to claim 1, wherein in step (3), the L-lactic acid oligomer obtained in step (2) is chargedHeating the lactide preparation kettle to 145-160 ℃ to melt the L-lactic acid oligomer; the catalyst used for synthesizing the L-lactide is a mixture of nickel oxide and molybdenum glycinate, the usage amount of the nickel oxide is 0.01 to 0.03 percent of the mass of the L-lactic acid oligomer, the usage amount of the molybdenum glycinate is 0.03 to 0.09 percent of the mass of the L-lactic acid oligomer, the reaction time is 3 to 5 hours, and the reaction pressure is 0.01 multiplied by 105Pa-0.1×105Pa；
Initial reaction: the mass ratio of the added nickel oxide to the added molybdenum glycinate is 1:2, and the addition amount of the nickel oxide during the initial reaction is 1/3 of the total addition amount of the nickel oxide;
when one third of the reaction time has elapsed: adding the rest nickel oxide into the lactide preparation kettle;
two thirds of the reaction time elapsed: adding the rest molybdenum glycinate into the lactide preparation kettle;
the preparation method of molybdenum glycinate comprises the following steps: mixing and stirring sodium molybdate and glycine hydroxy acid in a methanol solution at room temperature, and reacting for 2-3h to obtain solid molybdenum glycine hydroxy acid; the quantity ratio of glycine hydroxy acid to sodium molybdate is 4:1, and the concentration of sodium molybdate in the methanol solution is 0.1-2 mol/L;
the upper part of the lactide preparation kettle is communicated with the fluid of the condensation collection tank through a heat insulation pipeline, and the generated L-lactide is cooled and crystallized in the condensation collection tank.
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