CN1308367C - Condensation polymerization method for preparing hydroxylated acid condensation polymer - Google Patents

Abstract

A condensation polymerization method for preparing hydroxyacid polycondensates, characterized in that hydroxyacids or hydroxyacid oligomers carry out melt condensation polymerization or melt/solid phase condensation polymerization under the catalysis of ionic liquids without metal elements, High molecular weight, high-purity biodegradable polymer materials—hydroxy acid condensation polymers such as polylactic acid, polyglycolic acid or their copolymers are obtained. The obtained hydroxy acid polycondensate has the advantages of high purity and no residual metal elements; polylactic acid is synthesized by the condensation polymerization method of melt polycondensation or melt/solid phase polycondensation, which has the advantages of simple process, high efficiency, low cost, and no environmental pollution; The obtained polylactic acid has excellent biocompatibility, bioabsorbability and biodegradability, and also has the advantages of large molecular weight, high mechanical properties, and easy processing. It can not only be used in the fields of daily-use plastics and textile fibers, but also can As a biomedical material, it is used as a drug sustained release carrier, surgical implant material and tissue engineering scaffold material, etc.

Description

A kind of condensation polymerization method for preparing hydroxy acid polycondensate

technical field

The invention belongs to the technical field of polymer materials, and specifically relates to a condensation polymerization method for preparing hydroxyacid polycondensates, which is characterized in that hydroxyacids or hydroxyacid oligomers are melted under the catalytic action of a catalyst containing at least one ionic liquid Condensation polymerization or melt/solid phase condensation polymerization to obtain high-molecular-weight, high-purity biodegradable polymer materials—hydroxy acid condensation polymers such as polylactic acid, polyglycolic acid or their copolymers.

technical background

The vigorous development of the plastics industry has brought many high-performance polymer synthetic materials to human production and life, and has made positive contributions to promoting the development of society. However, with the rapid development of the polymer industry, polymer synthetic materials have also encountered two difficult problems: environmental pollution and resource shortage. Most of the polymer materials currently used, such as polyolefin, polystyrene, polyvinyl chloride, etc., are difficult to degrade naturally in nature, and these wastes have caused serious pollution to the environment, especially the so-called " White pollution” urgently needs to find a solution. At the same time, the raw materials for the production of these polymers all come from non-renewable fossil resources. With the continuous consumption of fossil resources, the energy crisis has become increasingly prominent, so the raw materials for the preparation of these polymers are also facing depletion. The use of biodegradable polymers derived from renewable resources is an essential means of addressing this problem at its source.

Aliphatic polyesters, including polylactic acid (PLA), polyglycolic acid (PGA), lactic acid-glycolic acid copolymer (PLGA), polycaprolactone (PCL) and their copolymers, have become the biochemical Research hotspots of degradable polymer materials. This is mainly because aliphatic polyester itself is non-toxic, non-irritating, and is a polymer with excellent biocompatibility, bioabsorbability and biodegradability. At the same time, aliphatic polyester also has the advantages of high mechanical properties and easy processing. This makes aliphatic polyesters not only useful as general-purpose plastics for daily-use plastics, agricultural films, textile fibers, etc., but also as biomedical materials, as drug sustained-release carriers, surgical implant materials (such as medical sutures, ophthalmic Implant materials, internal fixation materials for fractures and dressing materials for large area wounds (especially burns) and tissue engineering (such as artificial blood vessels and artificial skin), etc.

Among the aliphatic polyesters, polylactic acid (PLA), polyglycolic acid (PGA) and lactic acid-glycolic acid copolymer (PLGA) are the most important, commonly known as polylactic acid polymers. The large-scale application of polylactic acid polymers in the above fields depends on the efficient and low-cost preparation of high-quality (high purity, high molecular weight) polylactic acid polymer products. There are two main methods for preparing polylactic acid polymers: ring-opening polymerization (also known as two-step method) and direct condensation polymerization (also known as one-step method). The ring-opening polymerization method first obtains corresponding oligomers by condensation polymerization of hydroxy acids such as lactic acid (and/or glycolic acid), and depolymerizes the oligomers at high temperature to obtain crude lactide (and/or crude glycolide, and/or Crude glycolide), crude lactide (and/or crude glycolide, and/or crude glycolide) obtains pure lactide (and/or pure glycolide, and/or pure glycolide), pure lactide (and/or pure glycolide, and/or pure glycolide) is obtained by ring-opening polymerization of polylactic acid polymers (US 5023349, US 5374743, US 5142023，US 5247058，US 5247059，US5258488，US 5274073，US 5357035，US 5484881，US 6326458，US6376643，US 6007565，US 6004573，US 5952405，US 6255408，US4157437，EP 0299730，EP 0275581，CN 1068011C，CN 1167776A , CN1325913A, CN 1430676A). The ring-opening polymerization method is easy to obtain high-molecular-weight polymers, so it is the most important preparation method at present. For example, Cargill-Dow Company of the United States has built a production line with an annual output of 160,000 tons of polylactic acid. However, due to the lengthy production process of the two-step method, especially the low yield of the synthetic lactide monomer and the problems of high temperature, high vacuum, high energy consumption, and large equipment investment, the price of polylactic acid polymers is expensive, and it is difficult to compete with general-purpose plastics. , limiting its application and development.

The direct condensation polymerization method directly uses hydroxy acids such as lactic acid (and/or glycolic acid) as starting materials, and prepares polylactic acid polymers through dehydration condensation polymerization between hydroxyl and carboxyl functional groups. Such polymers prepared by condensation polymerization of hydroxy acids are often called hydroxy acid polycondensates. The condensation polymerization of hydroxy acids usually adopts the so-called melt polycondensation process, that is, the hydroxy acids are first dehydrated and condensed under normal pressure or low vacuum to obtain oligomers, and then undergo condensation polymerization in a molten state and high vacuum to obtain hydroxy acid polycondensation thing. Due to the sufficient sources of lactic acid and glycolic acid, the price is cheap, and the melt polycondensation process is simple and the equipment investment is low, the cost of polylactic acid can be greatly reduced. However, due to the complex balance between free hydroxy acid, water, polymer and lactide in the hydroxy acid melt polycondensation system, it is often difficult to obtain high molecular weight polymers (US 5,543,494, US 5,075,115, etc.), which is its shortcoming. Therefore, how to improve melt polycondensation to synthesize high molecular weight polylactic acid polymers has always been a research hotspot in this field.

In 1995, Japan's Mitsui Topress successfully developed a solution polycondensation process using high boiling point solvents (US 5770683, US 5310865, US 5428126, US 5440005, US 5444143), and obtained polylactic acid with a molecular weight of up to 300,000. Domestic researchers have also carried out research on solution polycondensation, and obtained polylactic acid with a molecular weight close to 100,000 (CN 1446836A, CN 1298892A). Due to the use of high-boiling-point solvents in the solution polycondensation method, the process of solvent separation and recovery is increased, which brings environmental pollution problems and increases production costs. Moreover, high-boiling-point solvents remain in the polymer, which affects the quality of the polymer.

The Chinese patent with the publication number CN 1326997A discloses a method for preparing polymer polylactic acid by using a dehydrating agent to promote condensation polymerization to obtain polylactic acid with an average molecular weight of 10,000 to 500,000, but the reaction time is too long, the amount of dehydrating agent is large and There are problems such as troublesome separation, low utilization rate of equipment, cumbersome operation, and high cost.

Publication No. CN 1557853A discloses a method for directly preparing polylactic acid by melt/solid-state polycondensation method, and obtains polylactic acid with a weight average molecular weight of 100,000-600,000, but the reaction time is relatively long.

Although the above-mentioned improvement on the condensation polymerization process can increase the molecular weight of the polymer, there are still obvious defects. In addition to the aforementioned problems such as solvent separation and recovery, solvent residue, environmental pollution, low equipment utilization, cumbersome operation, long reaction time, and high cost, these condensation polymerization processes all use catalysts containing metal elements, which brings about another concern The very important problems of the catalyst are (1) the catalyst is easily deactivated in acidic reactants such as lactic acid and glycolic acid, (2) the catalyst is difficult to dissolve and disperse in the reactant, (3) the metal catalyst remains in the obtained polymer product Thus affecting the biocompatibility and electrical properties of the product. Problems (1) and (2) affect the high efficiency of the preparation method, and problem (3) affects the purity and quality of the product, as follows.

Hydroxy acid condensation polymerization commonly used tin, zinc catalysts, such as stannous chloride, stannous octoate, zinc powder, zinc oxide and other metal or organometallic catalysts. Since these catalysts containing metal elements are easily deactivated in acidic reactants such as lactic acid and glycolic acid, if they are directly added to these stronger acidic reactants, they will not have the desired catalytic effect. Therefore, the hydroxy acid oligomer of a certain molecular weight is often synthesized first and then the catalyst is added, and the stability problem of the catalyst is solved because the acidity of the oligomer is greatly reduced. powder, tin powder, stannous oxide, zinc oxide) in hydroxy acid oligomers often have poor solubility and high viscosity of hydroxy acid oligomers, and it is difficult for the catalyst to dissolve and disperse well in hydroxy acid oligomers. Therefore, the catalytic effect is also affected. In addition, these metal-containing catalysts remain in the polymer product after the polycondensation reaction, which not only affects the properties of the polymer, such as electrical properties and degradability, but also adversely affects the biocompatibility of the polymer. The same is true for stannous octoate certified by the U.S. Food and Drug Administration (FDA), so there is still a certain potential safety hazard when used as a biomedical material. The problem of this metal catalyst residue not only exists in the polymer obtained by the direct polycondensation method, but also in the polymer obtained by the ring-opening polymerization method (such as stannous octoate, stannous chloride, zinc powder are often used in the ring-opening polymerization) , triisopropoxy aluminum and other catalysts containing metal elements). Since the removal of residual catalyst is not only technically difficult, but also costly, post-treatment for catalyst removal is generally not desired in industrial production.

Therefore, it is necessary to research and develop an efficient, low-cost, and pollution-free direct condensation polymerization method using a catalyst that does not contain metal elements, is stable in an acidic environment, and has good solubility and dispersibility to prepare high-molecular-weight, high-purity (without residual metal elements) ) hydroxyacid polycondensate is still a technical problem to be solved in the research and development of hydroxyacid polycondensate.

Contents of the invention

The invention provides a high-efficiency, low-cost, and non-environmental-pollution direct condensation polymerization method for preparing hydroxyacid polycondensates by using an efficient and non-toxic catalyst, through which the hydroxyl group with high molecular weight and high purity (no metal elements) can be prepared Acid polycondensate.

A condensation polymerization method for preparing hydroxyacid polycondensates, characterized in that hydroxyacids or hydroxyacid oligomers or a mixture of hydroxyacids and hydroxyacid oligomers, in the presence of a catalyst containing at least one metal-free ionic liquid Under catalysis, carry out melt condensation polymerization under the conditions of 100°C-190°C and 10 ³ Pa-1Pa for 2-72 hours to obtain a hydroxy acid polycondensate with a weight average molecular weight of 5,000-100,000; or the obtained hydroxy acid polycondensate is further Under the protection of inert gas or under the condition of vacuuming, carry out solid-state polycondensation at a temperature of 100°C to 170°C and a pressure of 1Pa to 2×10 ⁵ Pa, and react for 2 to 72 hours to obtain a weight average molecular weight of 50,000 ~200,000 polycondensates of hydroxy acids.

The hydroxy acid described in the present invention is selected from any one of lactic acid aqueous solution, L-lactic acid, D, L-lactic acid, glycolic acid, glycolic acid aqueous solution or a mixture thereof; the lactic acid aqueous solution is selected from L-lactic acid aqueous solution, D, L - Any one of the lactic acid aqueous solutions or a mixture thereof; the hydroxy acid oligomer is selected from low molecular weight homopolymers such as L, L-lactic acid oligomers, D, L-lactic acid oligomers, glycolic acid oligomers and L , Low molecular weight copolymers of L-lactic acid and D, L-lactic acid, low molecular weight copolymers of L, L-lactic acid and glycolic acid, low molecular weight copolymers of D, L-lactic acid and glycolic acid, etc. Any one or a mixture thereof; the weight-average molecular weight of the oligomer is 500-10,000.

The metal element-free ionic liquid described in the present invention is selected from any one of the ionic liquids composed of cation C ⁺ and anion Y ^m- and whose general structure is [C ⁺ ] _m [Y ^m- ] or a mixture thereof , where m=1 or 2, the general structural formula of the cation C ⁺ is:

Imidazoles N-Alkylpyridines Quaternary ammonium salts Quaternary phosphonium salts

cation cation cation cation cation cation

R ₁ , R ₂ , R ₃ , and R ₄ are selected from C ₁ -C ₁₂ alkyl, C ₃ -C ₁₂ branched chain alkyl, C ₅ -C ₁₂ cycloalkyl, substituted cycloalkyl, C ₂ -C ₆ Any one of alkenyl, aryl, substituted aryl, and aralkyl;

R ₅ is selected from any one of H atom, methyl group and ethyl group; anion Y ^{m- is} selected from Cl ^- , Br ^- , I ^- , PF ₆ ^- , BF ₄ ^- , [CF ₃ SO ₃ ] ^- , NO ₃ ^- , (CF ₃ SO ₂ ) ₂ N ^- , AlCl ₄ ^- , Al ₂ Cl ₇ ^- , SO ₄ ^2- , CH ₃ COO ^- , CF ₃ COO ^- , OH(CH ₃ )CHCOO ^- , CF ₃ SO ₃ ^- , any one of CF ₃ CF ₂ CF ₂ CF ₂ SO ₃ ^- , CF ₃ CF ₂ CF ₂ COO ^- .

The catalyst described in the present invention is an ionic liquid or a mixture of several ionic liquids.

Catalyst described in the present invention is the mixture of ionic liquid and nonionic liquid, and nonionic liquid catalyst is selected from any one in benzenesulfonic acid, p-toluenesulfonic acid, mycophenolic acid, boric acid, silicon dioxide or its Mixture; the molar ratio of the non-ionic liquid component to the ionic liquid component is 0.1-5:1.

The mass ratio of the molar weight of the catalyst in the present invention to the hydroxy acid or hydroxy acid oligomer or the mixture of hydroxy acid and hydroxy acid oligomer is 0.001˜0.2 mol:100 g.

The melt condensation polymerization reaction described in the present invention is carried out according to the following steps: the catalyst and the hydroxy acid are uniformly mixed in a ratio of 0.001 to 0.2 mol:100g, and the mixture is mixed at a temperature of 100°C to 170°C and a pressure of 1.013×10 ⁵ Pa to 10 ² Pa Under pressure, dehydration condensation reaction is carried out to obtain hydroxy acid oligomer; then the obtained hydroxy acid oligomer is subjected to melt polycondensation at a temperature of 100°C to 190°C and a pressure of 10 ³ Pa to 1 Pa, and reacts for 2 to 72 hours to obtain Hydroxy-acid condensation polymer with weight average molecular weight of 5,000-100,000.

The melt condensation polymerization reaction described in the present invention is carried out according to the following steps: the hydroxy acid is first dehydrated and condensed at a temperature of 100°C to 170°C and a pressure of 1.013×10 ⁵ Pa to 10 ² Pa to obtain a hydroxy acid oligomer Then add a catalyst containing at least one ionic liquid to the obtained hydroxyacid oligomer, the ratio of the catalyst to the hydroxyacid oligomer mass is 0.001～0.2mol: 100g, mix evenly, at a temperature of 100°C～190°C Melt polycondensation is carried out under a pressure of 10 ³ Pa to 1 Pa, and the reaction is carried out for 2 to 72 hours to obtain a hydroxy acid polycondensate with a weight average molecular weight of 5,000 to 100,000.

The melt/solid phase condensation polymerization reaction described in the present invention is carried out according to the following steps: the above-mentioned weight-average molecular weight is 5000～100000 hydroxyacid polycondensate, after pulverizing, the granular hydroxyacid polycondensate with a particle size of 10 μm～5mm is obtained, and the Under gas protection or under vacuum conditions, carry out solid phase polycondensation at a temperature of 100°C to 170°C and a pressure of 1Pa to 2×10 ⁵ Pa, and react for 2 to 72 hours to obtain hydroxyl groups with a weight average molecular weight of 50,000 to 200,000 Acid polycondensate.

The method of the present invention uses an ionic liquid that does not contain metal elements as a catalyst, avoiding the influence of the residual metal catalyst on the biocompatibility and electrical properties of the obtained polylactic acid when the metal-containing catalyst is usually used, and the obtained polylactic acid has high purity and no residual metal. Advantages of the catalyst; the method of the present invention adopts melt polycondensation and melt/solid phase polycondensation to synthesize polylactic acid in one step, and has the advantages of simple process, high efficiency, low cost and no environmental pollution. The polylactic acid obtained in the present invention has excellent biocompatibility, bioabsorbability and biodegradability, and also has the advantages of large molecular weight, high mechanical properties, and easy processing, so it can not only be used in the fields of daily-use plastics, textile fibers, etc. , and can be used as biomedical materials, as drug sustained-release carriers, surgical implant materials and tissue engineering scaffold materials.

The method of the present invention adopts "green" ionic liquid as a catalyst to catalyze condensation polymerization, and the obtained polylactic acid is also a biodegradable material, which is a combination of a "green" polymerization method and a "green" polymer. Today, the energy crisis is becoming more and more prominent, which is of great significance.

In the present invention, either a single ionic liquid can be used as a catalyst, or a mixture of two or two ionic liquids can be used as a catalyst.

In the present invention, the molar ratio of the catalyst containing at least one ionic liquid to the mass of the hydroxyacid or hydroxyacid oligomer as the reaction starting material is preferably 0.005mol/100g-0.05mol/100g.

The catalyst used in combination with the ionic liquid in the present invention is preferably selected from benzenesulfonic acid and p-toluenesulfonic acid.

In the present invention, the ionic liquid can remain stable in the weakly acidic environment of the hydroxyacid reactant without decomposition, so it can be directly added to the hydroxyacid to play a catalytic role in the dehydration stage, solving the common The defect that the metal element-containing catalyst cannot be directly added to the hydroxy acid reactant because it is easily deactivated in a strong acidic environment improves the catalytic effect of the catalyst.

In the present invention, the ionic liquid is easy to dissolve and disperse in hydroxyacid or hydroxyacid oligomer, and overcomes the difficulty of dissolving common metal element-containing catalysts (such as tin powder, zinc powder, stannous oxide, zinc oxide) , Difficult to disperse, thus further improving the catalytic effect of the catalyst.

In the present invention, because the ionic liquid has excellent stability and solubility and dispersibility, it can be directly added to the lactic acid monomer or the aqueous solution of the lactic acid monomer, or it can be added after synthesizing the lactic acid oligomer. Both methods have good catalytic effect and improve the flexibility of process operation.

In the present invention, the synthesis of the ionic liquid is simple, the raw materials are easy to obtain, and most of them are sold as commercial products or reagents. For the synthesis method, refer to open literature, such as CN 1521163A, CN 1417407A.

In the present invention, the reaction starter hydroxyacid oligomer is selected from L, L-lactic acid oligomer, D, L-lactic acid oligomer, glycolic acid oligomer and other low molecular weight homopolymers and L, L-lactic acid oligomer Any one of low molecular weight copolymers such as low molecular weight copolymers of D, L-lactic acid, low molecular weight copolymers of L, L-lactic acid and glycolic acid, low molecular weight copolymers of D, L-lactic acid and glycolic acid, or Its mixture; the weight average molecular weight of the oligomer is 500-10000, preferably 1000-7000.

In the present invention, the lactic acid oligomer is prepared from lactic acid or lactic acid aqueous solution by conventional dehydration polycondensation method. In the oligomer preparation process, no catalyst can be added, and the catalyst containing at least one ionic liquid described in the present invention can also be added, but the commonly used catalyst containing metal elements can not be added.

The present invention uses ionic liquid as a catalyst to prepare the condensation polymerization method of hydroxyacid polycondensate, which can adopt the melt polycondensation method, and can also continue to carry out solid phase polycondensation after melt polymerization, that is, the melt/solid phase polymerization method, to further increase the molecular weight of polylactic acid .

In the present invention, the temperature for preparing the hydroxy acid oligomer is preferably 110° C. to 150° C., and the pressure is preferably 1000 Pa to 1.013×10 ⁵ Pa.

In the present invention, the temperature in the melt polycondensation stage is preferably 150° C. to 185° C., and the pressure is preferably 100 Pa to 500 Pa.

In the present invention, the temperature in the solid phase polycondensation stage is preferably 100°C to 170°C, the pressure is preferably 1.013×10 ⁵ Pa to 1.5×10 ⁵ Pa when the inert gas is used for protection, and the pressure is preferably 1 Pa to 200 Pa when vacuuming for solid phase polycondensation.

The method provided by the invention can synthesize the hydroxy acid polycondensate with a weight average molecular weight of 5000-200000. The determination of the molecular weight is carried out by methods commonly used in the polymer field, such as end group titration, intrinsic viscosity method and gel permeation chromatography (GPC) determination.

Detailed ways

The embodiments of the present invention will be further described below through examples, but the scope of the present invention is not limited to these examples.

Example 1

Add 50 grams of 90% L-lactic acid aqueous solution into a 250 mL three-necked round bottom flask, start magnetic stirring, and heat in an oil bath. Dehydrate at 100°C and normal pressure for 2 hours; then gradually reduce the pressure to 1300Pa (10 mm Hg), raise the temperature to 130°C, and dehydrate for 2 hours; obtain L-lactic acid oligomerization with a weight average molecular weight of 520 Then continue dehydration for 4 hours at 150° C. and 520 Pa (4 mm Hg), to obtain a lactic acid oligomer with a weight average molecular weight of 1610. After cooling, add 0.002 moles of methyltriphenylphosphonium bromide to a three-necked round-bottomed flask, mix well, gradually raise the temperature to 170°C, and gradually reduce the pressure to 130Pa (1 mm Hg), After reacting for 10 hours, the yield of polylactic acid was 90.5%, the weight average molecular weight measured by gel permeation chromatography was 12870, and the polydispersity index was 1.36.

Example 2

The preparation of lactic acid oligomer was as in Example 1. Add 0.002 mole of tetrabutylammonium chloride in the lactic acid oligomer of gained, gradually warming up to 170 ℃, gradually reducing pressure to 130Pa (1 mm Hg), react for 10 hours, the productive rate of polylactic acid is 84.7%, The weight average molecular weight measured by gel permeation chromatography was 6870, and the polydispersity index was 1.48.

Example 3

The preparation of lactic acid oligomer was as in Example 1. Add 0.004 mole of N-butylpyridine bromide to the obtained lactic acid oligomer, gradually heat up to 170°C, gradually reduce the pressure to 130Pa (1 mm Hg), react for 10 hours, and the yield of polylactic acid is 93.1%. , the weight average molecular weight measured by gel permeation chromatography is 11000, and the polydispersity index is 1.26.

Example 4

The preparation of lactic acid oligomer was as in Example 1. Add 0.005 mole of 1-butyl-3-methylimidazolium bromide (bmimBr) to the obtained lactic acid oligomer, gradually heat up to 190°C, gradually depressurize to 130Pa (1 mm Hg), react for 10 hours, The yield of polylactic acid is 84.2%, the weight average molecular weight measured by gel permeation chromatography is 9610, and the polydispersity index is 1.44.

Example 5

Add 50 g of 90% L-lactic acid aqueous solution and 0.0025 mole of 1-ethyl-3-methylimidazolium hexafluorophosphate (emimPF ₆ ) into a 250 mL three-neck round bottom flask, start magnetic stirring, and heat in an oil bath. React at 110°C and normal pressure for 3 hours, then gradually reduce the pressure to 1330Pa (10 mmHg), raise the temperature to 130°C, react for 3 hours, then at 150°C, 130Pa (1 mmHg) The reaction was carried out at 170° C. and 130 Pa (1 mm Hg) for 13 hours. The yield of polylactic acid is 83.4%, the weight average molecular weight measured by gel permeation chromatography is 5970, and the polydispersity index is 1.39.

Example 6

Add 50 grams of 90% L-lactic acid aqueous solution into a 250 mL three-neck round bottom flask, start magnetic stirring, and heat in an oil bath. Dehydrate at 110°C and normal pressure for 2 hours; then gradually reduce the pressure to 1330Pa (10 mmHg), raise the temperature to 130°C, and dehydrate for 2 hours; then at 150°C, 520Pa (4 mmHg) Continue dehydration for 4 hours at 170°C and 100Pa for 10 hours to obtain an L-lactic acid oligomer with a weight average molecular weight of 7360. Add 0.002 mole of 1-butyl-3-methylimidazolium chloride (bmimCl), react for 20 hours under 170°C and 133Pa, the yield of polylactic acid is 88.1%, and the weight-average molecular weight measured by gel permeation chromatography is 28860 with a polydispersity index of 1.32.

Example 7

The preparation of lactic acid oligomer was as in Example 1. After cooling, 0.002 mole of 1-butyl-3-methylimidazolium trifluoroacetate was added to the flask, the temperature was gradually raised to 170° C., and the pressure was gradually reduced to 10 ³ Pa for reaction for 10 hours. The yield of polylactic acid is 68.8%, the weight average molecular weight measured by gel permeation chromatography is 17310, and the polydispersity index is 1.63.

Example 8

The preparation of lactic acid oligomer was as in Example 1. Add 0.002 mole of 1-ethyl-3-methylimidazolium bromide (emimBr) to the obtained lactic acid oligomer, gradually increase the temperature to 170° C., gradually reduce the pressure to 133 Pa (1 mm Hg), and react for 10 hours; After cooling, 0.004 mol of 1-butyl-3-methylimidazolium chloride (bmimCl) was added, the temperature was gradually raised to 180° C., and the pressure was gradually reduced to 70 Pa (0.5 mmHg), and the reaction was carried out for 20 hours. The yield of polylactic acid is 80.4%, the weight average molecular weight measured by gel permeation chromatography is 32638, and the polydispersity index is 1.23.

Example 9

The preparation of lactic acid oligomer was as in Example 1. Add 0.002 mole of 1,3-dibutylimidazole L-lactate and 0.002 mole of 1-butyl-3-methylimidazole acetate (bmimCOOCH ₃ ) to the resulting lactic acid oligomer, and gradually heat up to 170°C, gradually reduce the pressure to 130Pa, and react for 10 hours. The yield of polylactic acid is 94.0%, the weight average molecular weight measured by gel permeation chromatography is 29350, and the polydispersity index is 1.35.

Example 10

The preparation of lactic acid oligomer was as in Example 1. Add 0.08 mole of 1-hexyl-3-methylimidazolium acetate (hmimCOOCH ₃ ) to the obtained lactic acid oligomer, gradually raise the temperature to 170° C., gradually reduce the pressure to 133 Pa, and react for 10 hours. The yield of polylactic acid is 81.4%, the weight average molecular weight measured by gel permeation chromatography is 19306, and the polydispersity index is 1.33.

Example 11

The preparation of lactic acid oligomer was as in Example 1. Add 0.001 mole of 1-ethyl-2,3-dimethylimidazolium perfluorobutyrate and 0.005 mole of silicon dioxide to the obtained lactic acid oligomer, gradually raise the temperature to 170°C, and gradually reduce the pressure to 133Pa, React for 15 hours. The yield of polylactic acid is 83.6%, the weight average molecular weight measured by gel permeation chromatography is 16420, and the polydispersity index is 1.66.

Example 12

Add 50 grams of 90% D,L-lactic acid aqueous solution into a 250 mL three-neck round bottom flask, start magnetic stirring, and heat in an oil bath. Dehydrate at 110°C and normal pressure for 2 hours; then gradually reduce the pressure to 1330Pa (10 mmHg), raise the temperature to 130°C, and dehydrate for 2 hours; then at 150°C, 520Pa (4 mmHg) Continue dehydration for 4 hours. Add 0.005 moles of 1-ethyl-3-methylimidazole D, L-lactate, gradually increase the temperature to 170°C, gradually reduce the pressure to 133Pa, and react for 20 hours. The yield of polylactic acid is 84.5%. The weight average molecular weight measured by permeation chromatography is 25950, and the polydispersity index is 1.48.

Example 13

The preparation of lactic acid oligomer was as in Example 1. Add 0.002 moles of 1,3-diethylimidazole L-lactate and 0.0002 moles of p-toluenesulfonic acid to the obtained lactic acid oligomers, gradually raise the temperature to 170°C, gradually reduce the pressure to 130Pa, and react for 10 Hour. Continue to heat up to 180°C, gradually decompress to 70Pa (0.5 mm Hg), react for 20 hours, the yield of polylactic acid is 82.1%, the weight average molecular weight measured by gel permeation chromatography is 33140, and the polydispersity index is 1.37 .

Example 14

The preparation of lactic acid oligomer was as in Example 1. Add 0.004 mole of 1,3-diethylimidazole L-lactate to the obtained lactic acid oligomer, gradually raise the temperature to 170° C., gradually reduce the pressure to 130 Pa, and react for 10 hours. Then the temperature was raised to 180° C., the pressure was gradually reduced to 1 Pa, and the reaction was carried out for 48 hours. The yield of polylactic acid was 79.2%. The weight average molecular weight was 46310 and the polydispersity index was 1.53 as measured by gel permeation chromatography.

Example 15

The preparation of lactic acid oligomer was as in Example 1. In the obtained lactic acid oligomer, add 0.002 mole of 1,3-diethylimidazole L-lactate and benzenesulfonic acid of equimolar amount in the flask, gradually heat up to 170°C, gradually decompress to 400Pa (3 mmHg), reacted for 10 hours, then gradually increased the temperature to 180°C, gradually reduced the pressure to 260Pa (2 mmHg), reacted for 20 hours, and obtained polylactic acid with a weight average molecular weight of 39200. After cooling, take out and pulverize, sieve, and crystallize polylactic acid particles with a particle size of 5mm at 105°C and 130Pa for 2 hours, then gradually increase the temperature to 150°C, reduce the pressure to 70Pa (0.5 mm Hg), and react for 5 hours Finally, polylactic acid with a weight average molecular weight of 43,400 was obtained; then, the temperature was gradually raised to 160° C., and the pressure was reduced to 10 Pa. After 10 hours, polylactic acid with a weight average molecular weight of 53,900 was obtained, and after 20 hours, polylactic acid with a weight average molecular weight of 66,640 was obtained; continue Gradually raise the temperature to 1670°C and reduce the pressure to 1Pa. After 20 hours, polylactic acid with a weight average molecular weight of 78,800 is obtained, and after 30 hours, polylactic acid with a weight average molecular weight of 89,630 is obtained.

Example 16

The preparation of lactic acid oligomer was as in Example 1. Add 0.004 mole of 1-ethyl-3-methylimidazole acetate (emimCOOCH ₃ ) and p-toluenesulfonic acid (TSA) in equimolar amounts to the obtained lactic acid oligomer, and gradually raise the temperature to 170°C, Gradually reduce the pressure to 260Pa (2 mm Hg), react for 20 hours, then gradually increase the temperature to 180°C, gradually reduce the pressure to 130Pa, and react for 48 hours to obtain polylactic acid with a weight average molecular weight of 89300. After cooling, take out and pulverize, sieve, put the obtained polylactic acid particles with a particle size of 10 μm into a three-necked flask, pass through _N2 continuously for protection, keep the pressure at 2×10 ⁵ Pa, gradually raise the temperature to 105°C, and crystallize 2 Hours; then heat up to 120°C, crystallize for 4 hours; then heat up to 135°C, crystallize for 4 hours; gradually heat up to 150°C, react for 15 hours to obtain polylactic acid with a weight average molecular weight of 115,200, and after 25 hours, obtain a weight average molecular weight of 136600 polylactic acid, polylactic acid with a weight average molecular weight of 162400 was obtained after 35 hours, polylactic acid with a weight average molecular weight of 175000 was obtained after 45 hours, and polylactic acid with a weight average molecular weight of 184700 was obtained after 60 hours.

Example 17

Add 20 grams of glycolic acid into a 100 mL three-neck round bottom flask, start magnetic stirring, and heat in an oil bath. Dehydrate at 110°C and normal pressure for 2 hours, then gradually reduce the pressure to 1300Pa (10 mm Hg), raise the temperature to 130°C, dehydrate for 2 hours, then continue to dehydrate at 150°C and 130Pa for 4 hours. Add 0.04 moles of 1-butyl-3-methylimidazolium chloride (bmimCl), gradually raise the temperature to 170°C, gradually reduce the pressure to 540Pa, react for 10 hours, then gradually raise the temperature to 180°C, gradually reduce the pressure to 130Pa, and react 10 hours. Remove after cooling. Since the PGA obtained by the direct polycondensation method is insoluble in common organic solvents, the molecular weight was not determined.

Example 18

5 grams of glycolic acid and 20 grams of lactic acid were added to a 100 mL three-neck round bottom flask, and then 0.003 moles of 1-butyl-3-methylimidazolium chloride (bmimCl) was added. Start the magnetic stirring and heat the oil bath. React at 110°C and normal pressure for 2 hours; then gradually reduce the pressure to 1300Pa, raise the temperature to 130°C, and react for 2 hours; then continue to react at 150°C and 520Pa for 4 hours. Then gradually raise the temperature to 170°C, gradually reduce the pressure to 260Pa (2 mmHg), and react for 10 hours, then gradually raise the temperature to 180°C, gradually reduce the pressure to 130Pa, and react for 10 hours. The yield of PLGA is 83.9%, the weight average molecular weight measured by gel permeation chromatography is 26410, and the polydispersity index is 1.37.

Claims (9)

1, a kind of condensation polymerization method for preparing hydroxylated acid condensation polymer, the mixture that it is characterized in that alcohol acid or alcoholic acid oligomer or alcohol acid and alcoholic acid oligomer, under the catalysis of the ion liquid catalyzer that contains a kind of not containing metal element at least, at 100 ℃～190 ℃, 10 ³Carry out melt condensation polymerization under the condition of Pa～1Pa 2～72 hours, and obtained weight-average molecular weight and be 5000～100 000 hydroxylated acid condensation polymer; Perhaps resulting hydroxylated acid condensation polymer is further under protection of inert gas or under the condition that is vacuumizing, in 100 ℃～170 ℃ temperature and 1Pa～2 * 10 ⁵Under the pressure of Pa, carry out solid phase polycondensation, reacted 2～72 hours, obtain weight-average molecular weight and be 50 000～200 000 hydroxylated acid condensation polymer.

2, the condensation polymerization method of preparation hydroxylated acid condensation polymer as claimed in claim 1 is characterized in that described alcohol acid is selected from lactic acid aqueous solution, L-lactic acid, D, any one or its mixture in L-lactic acid, oxyacetic acid, the hydroxy acid solution; Lactic acid aqueous solution is selected from L-lactic acid aqueous solution, D, any one or its mixture in the L-lactic acid aqueous solution; Alcoholic acid oligomer is selected from L, L-lactic acid oligomer, D, low molecular mass homopolymers and L such as L-lactic acid oligomer, glycolic acid oligomers, L-lactic acid and D, the low-molecular weight copolymer of L-lactic acid, L, the low-molecular weight copolymer of L-lactic acid and oxyacetic acid, D, any one or its mixture in the low-molecular weight copolymers such as low-molecular weight copolymer of L-lactic acid and oxyacetic acid; The weight-average molecular weight of oligopolymer is 500～10000.

3, the condensation polymerization method of preparation hydroxylated acid condensation polymer as claimed in claim 1 is characterized in that described ionic liquid is selected from by positively charged ion C ⁺With negatively charged ion Y ^M-Composition and general structure are [C ⁺] _m[Y ^M-] ionic liquid in any one or its mixture; In the formula, m=1 or 2, positively charged ion C ⁺General structure be:

Imidazoles N-alkyl pyridine class quaternary ammonium salt quaternary phosphine salt

Positively charged ion positively charged ion positively charged ion positively charged ion

R ₁, R ₂, R ₃, R ₄Be selected from C ₁～C ₁₂Alkyl, C ₃～C ₁₂Branched-chain alkyl, C ₅～C ₁₂Cycloalkyl, substituted cycloalkyl, C ₂～C ₆In thiazolinyl, aryl, substituted aryl, the aralkyl any one; R ₅Be selected from H atom, methyl, the ethyl any one; Negatively charged ion Y ^M-Be selected from Cl ^-, Br ^-, I ^-, PF ₆ ^-, BF ₄ ^-, [CF ₃SO ₃] ^-, NO ₃ ^-, (CF ₃SO ₂) ₂N ^-, AlCl ₄ ^-, Al ₂Cl ₇ ^-, SO ₄ ^2-, CH ₃COO ^-, CF ₃COO ^-, OH (CH ₃) CHCOO ^-, CF ₃SO ₃ ^-, CF ₃CF ₂CF ₂CF ₂SO ₃ ^-, CF ₃CF ₂CF ₂COO ^-In any one.

4, the condensation polymerization method of preparation hydroxylated acid condensation polymer as claimed in claim 1 is characterized in that described catalyzer is a kind of ionic liquid or several ion liquid mixture.

5, the condensation polymerization method of preparation hydroxylated acid condensation polymer as claimed in claim 1, it is characterized in that described catalyzer is ionic liquid and nonionic mixtures of liquids, the nonionic liquid catalyst is selected from any one or its mixture in Phenylsulfonic acid, p-methyl benzenesulfonic acid, mycophenolic acid, boric acid, the silicon-dioxide; The mol ratio of nonionic liquid ingredient and ionic liquid constituents is 0.1～5: 1.

6, the condensation polymerization method of preparation hydroxylated acid condensation polymer as claimed in claim 1 is characterized in that the mass ratio of the mixture of the molar weight of described catalyzer and alcohol acid or alcoholic acid oligomer or alcohol acid and alcoholic acid oligomer is 0.001～0.2mol: 100g.

7, the condensation polymerization method of preparation hydroxylated acid condensation polymer as claimed in claim 1, it is characterized in that the reaction of described melt condensation polymerization carries out according to the following steps: catalyzer, alcohol acid are even by the mixed of 0.001～0.2mol: 100g, 100 ℃～170 ℃ temperature and 1.013 * 10 ⁵Pa～10 ²Under the pressure of Pa, carry out dehydration condensation, obtain alcoholic acid oligomer; The gained alcoholic acid oligomer is 100 ℃～190 ℃ temperature and 10 then ³Carry out melt phase polycondensation under the pressure of Pa～1Pa, reacted 2～72 hours, obtain weight-average molecular weight and be 5000～100000 hydroxylated acid condensation polymer.

8, the condensation polymerization method of preparation hydroxylated acid condensation polymer as claimed in claim 1 is characterized in that the reaction of described melt condensation polymerization carries out according to the following steps: alcohol acid is at first 100 ℃～170 ℃ temperature and 1.013 * 10 ⁵Pa～10 ²Under the pressure of Pa, carry out dehydration condensation, obtain alcoholic acid oligomer; Add in the gained alcoholic acid oligomer then and contain a kind of ion liquid catalyzer at least, the ratio of catalyzer and alcoholic acid oligomer quality is 0.001～0.2mol: 100g, mixes, 100 ℃～190 ℃ temperature and 10 ³Carry out melt phase polycondensation under the pressure of Pa～1Pa, reacted 2～72 hours, obtain weight-average molecular weight and be 5000～100000 hydroxylated acid condensation polymer.

9, the condensation polymerization method of preparation hydroxylated acid condensation polymer as claimed in claim 1; it is characterized in that described fusion/solid phase condensation polyreaction carries out according to the following steps: above-mentioned weight-average molecular weight is 5 000～100 000 hydroxylated acid condensation polymer; obtain the granular hydroxylated acid condensation polymer that particle diameter is 10 μ m～5mm through pulverizing; under protection of inert gas or under vacuum condition, in 100 ℃～170 ℃ temperature and 1Pa～2 * 10 ⁵Under the pressure of Pa, carry out solid phase polycondensation, reacted 2～72 hours, obtain weight-average molecular weight and be 50 000～200 000 hydroxylated acid condensation polymer.