CN1308367C - Condensation polymerization method for preparing hydroxylated acid condensation polymer - Google Patents
Condensation polymerization method for preparing hydroxylated acid condensation polymer Download PDFInfo
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- CN1308367C CN1308367C CNB2005100607053A CN200510060705A CN1308367C CN 1308367 C CN1308367 C CN 1308367C CN B2005100607053 A CNB2005100607053 A CN B2005100607053A CN 200510060705 A CN200510060705 A CN 200510060705A CN 1308367 C CN1308367 C CN 1308367C
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- acid
- lactic acid
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- 239000002253 acid Substances 0.000 title claims abstract description 116
- 238000009833 condensation Methods 0.000 title claims abstract description 49
- 230000005494 condensation Effects 0.000 title claims abstract description 49
- 229920000642 polymer Polymers 0.000 title claims abstract description 47
- 238000000034 method Methods 0.000 title claims abstract description 43
- 238000012643 polycondensation polymerization Methods 0.000 title claims abstract description 36
- 229910052751 metal Inorganic materials 0.000 claims abstract description 22
- 239000002608 ionic liquid Substances 0.000 claims abstract description 21
- 239000007790 solid phase Substances 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- 229920001577 copolymer Polymers 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 150000001261 hydroxy acids Chemical class 0.000 claims abstract description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 81
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 claims description 65
- 235000014655 lactic acid Nutrition 0.000 claims description 41
- 239000004310 lactic acid Substances 0.000 claims description 41
- 230000001476 alcoholic effect Effects 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 28
- 238000006068 polycondensation reaction Methods 0.000 claims description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- 150000002500 ions Chemical class 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 23
- 239000002184 metal Substances 0.000 claims description 17
- 239000007788 liquid Substances 0.000 claims description 16
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 230000018044 dehydration Effects 0.000 claims description 13
- 238000006297 dehydration reaction Methods 0.000 claims description 13
- 239000012071 phase Substances 0.000 claims description 10
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 230000004927 fusion Effects 0.000 claims description 6
- 239000011261 inert gas Substances 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 5
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 4
- 229920001519 homopolymer Polymers 0.000 claims description 3
- 229960001866 silicon dioxide Drugs 0.000 claims description 3
- 235000012239 silicon dioxide Nutrition 0.000 claims description 3
- 239000000377 silicon dioxide Substances 0.000 claims description 3
- 229910016467 AlCl 4 Inorganic materials 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004327 boric acid Substances 0.000 claims description 2
- 229960002645 boric acid Drugs 0.000 claims description 2
- 238000006555 catalytic reaction Methods 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 150000002460 imidazoles Chemical class 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 claims description 2
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 claims description 2
- 229960000951 mycophenolic acid Drugs 0.000 claims description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 2
- 229920000747 poly(lactic acid) Polymers 0.000 abstract description 57
- 239000004626 polylactic acid Substances 0.000 abstract description 11
- 239000000463 material Substances 0.000 abstract description 10
- 230000003197 catalytic effect Effects 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 3
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- 239000000969 carrier Substances 0.000 abstract 1
- 239000000835 fiber Substances 0.000 abstract 1
- 238000002513 implantation Methods 0.000 abstract 1
- 239000012567 medical material Substances 0.000 abstract 1
- -1 poly(lactic acid) Polymers 0.000 description 93
- 238000010792 warming Methods 0.000 description 23
- 238000005227 gel permeation chromatography Methods 0.000 description 17
- 239000000126 substance Substances 0.000 description 11
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 10
- 229920005601 base polymer Polymers 0.000 description 8
- 238000006116 polymerization reaction Methods 0.000 description 7
- 229920000954 Polyglycolide Polymers 0.000 description 6
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 6
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- 239000004033 plastic Substances 0.000 description 6
- 239000004633 polyglycolic acid Substances 0.000 description 6
- 239000000376 reactant Substances 0.000 description 6
- 238000007151 ring opening polymerisation reaction Methods 0.000 description 6
- KAIPKTYOBMEXRR-UHFFFAOYSA-N 1-butyl-3-methyl-2h-imidazole Chemical compound CCCCN1CN(C)C=C1 KAIPKTYOBMEXRR-UHFFFAOYSA-N 0.000 description 5
- 229920003232 aliphatic polyester Polymers 0.000 description 5
- 238000003912 environmental pollution Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- IBZJNLWLRUHZIX-UHFFFAOYSA-N 1-ethyl-3-methyl-2h-imidazole Chemical compound CCN1CN(C)C=C1 IBZJNLWLRUHZIX-UHFFFAOYSA-N 0.000 description 3
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 3
- 239000003519 biomedical and dental material Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 3
- 239000011787 zinc oxide Substances 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
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- 238000011161 development Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
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- 229920006158 high molecular weight polymer Polymers 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229920001610 polycaprolactone Polymers 0.000 description 2
- 239000004632 polycaprolactone Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229920002994 synthetic fiber Polymers 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HCGMDEACZUKNDY-UHFFFAOYSA-N 1-butyl-3-methyl-1,2-dihydroimidazol-1-ium;acetate Chemical compound CC(O)=O.CCCCN1CN(C)C=C1 HCGMDEACZUKNDY-UHFFFAOYSA-N 0.000 description 1
- DVYSHWKJRYAQOJ-UHFFFAOYSA-N 1-butyl-3-methyl-2h-imidazole;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCCCN1CN(C)C=C1 DVYSHWKJRYAQOJ-UHFFFAOYSA-N 0.000 description 1
- KVBQNFMTEUEOCD-UHFFFAOYSA-M 1-butylpyridin-1-ium;bromide Chemical compound [Br-].CCCC[N+]1=CC=CC=C1 KVBQNFMTEUEOCD-UHFFFAOYSA-M 0.000 description 1
- WGVGZVWOOMIJRK-UHFFFAOYSA-N 1-hexyl-3-methyl-2h-imidazole Chemical compound CCCCCCN1CN(C)C=C1 WGVGZVWOOMIJRK-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- YPJUNDFVDDCYIH-UHFFFAOYSA-M 2,2,3,3,4,4,4-heptafluorobutanoate Chemical compound [O-]C(=O)C(F)(F)C(F)(F)C(F)(F)F YPJUNDFVDDCYIH-UHFFFAOYSA-M 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
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- 125000002524 organometallic group Chemical group 0.000 description 1
- REPWBKQJAMXHFL-UHFFFAOYSA-N phenylphosphane;hydrobromide Chemical class [Br-].[PH3+]C1=CC=CC=C1 REPWBKQJAMXHFL-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
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Abstract
The present invention relates to a condensation polymerization method for preparing hydroxy acidcondensation polymers, which is characterized in that hydroxy acid or hydroxy acid oligomers are used for a melt condensation polymerization reaction or a melt / solid phase condensation polymerization reaction under the catalytic action of ionic liquid in order to obtain polylactic acid, polyglycollic acid or the copolymer of the polylactic acid and the polyglycollic acid and other hydroxy acid condensation polymers. Compared with the prior art, the present invention has the advantages that ionic liquid without metallic elements is used as a catalyst, and the obtained hydroxy acid condensation polymers do not contain the metallic elements; polylactic acid is synthesized by the condensation polymerization method for melt condensation polymerization or melt / solid phase condensation polymerization, and the present invention has the advantages of simple manufacturing process, high efficiency, low cost, no environment pollution, good biocompatibility, biologic absorbability and biodegradability, large molecular weight, high mechanical property, easy processing, etc. The present invention can be applied to the fields of commodity plastics, textile fiber, etc., and can be used for biologic medical materials such as drug release carriers, surgery implantation materials, tissue engineering support materials, etc.
Description
Technical field
The invention belongs to technical field of polymer materials, be specially a kind of condensation polymerization method for preparing hydroxylated acid condensation polymer, it is characterized in that alcohol acid or alcoholic acid oligomer are under the katalysis that contains a kind of ion liquid catalyzer at least, carry out melt condensation polymerization reaction or fusion/solid phase condensation polyreaction, obtain hydroxylated acid condensation polymers such as high molecular, highly purified biodegradable polymer-poly(lactic acid), polyglycolic acid or its multipolymer.
Technical background
The flourish of plastics industry is the high molecular synthetic material that Human's production, life have brought many excellent propertys, for positive contribution has been made in the development that promotes society.Yet along with developing rapidly of polymer industry, high molecular synthetic material has also run into two insoluble problems: environmental pollution and shortage of resources.Most of macromolecular materials that use such as polyolefine, polystyrene, polyvinyl chloride etc. are difficult to natural degradation at occurring in nature at present, these wastes have caused serious pollution to environment, the what is called " white pollution " that particularly disposable daily plastic brings is badly in need of finding terms of settlement.The raw material of producing these polymkeric substance simultaneously all comes from non-renewable fossil resource, and along with the continuous consumption of fossil resource, energy dilemma also becomes increasingly conspicuous, thereby the raw material for preparing these polymkeric substance also faces exhaustion.The biodegradable polymers that use derives from renewable resources is the fundamental means that addresses this problem from the source.
The aliphatic polyester that comprises poly(lactic acid) (PLA), polyglycolic acid (PGA) and poly lactic coglycolic acid (PLGA), polycaprolactone (PCL) and multipolymer thereof etc. is the domestic and international research focus of biodegradable polymer in recent years.This mainly is that nonirritant is a kind of polymer with good biocompatibility, Bioabsorbable and biodegradability because aliphatic polyester itself is nontoxic.Simultaneously, aliphatic polyester also has advantages such as mechanical property height, easy processing.This makes aliphatic polyester not only can be used as general-purpose plastics to be used for fields such as daily plastic, agricultural film, textile fibres, and can be used as biomedical material, be used as slow releasing carrier of medication, surgery embedded material (as the wrapper material of suture, ophthalmology embedded material, bone fracture internal fixation material and extensive wound (especially burn)) and organizational project (as artificial blood vessel and artificial skin) etc.
Be most important with poly(lactic acid) (PLA), polyglycolic acid (PGA) and poly lactic coglycolic acid (PLGA) in the aliphatic polyester, be commonly referred to polylactic acid base polymer.The large-scale application of polylactic acid base polymer in above-mentioned field depends on efficiently, prepares at low cost the polylactic acid base polymer product of high quality (high purity, high molecular).The preparation method of polylactic acid base polymer mainly contains two kinds: ring-opening polymerization method (claim not only two step method) and direct polymerization method (but also claiming single stage method).The ring-opening polymerization method at first obtains corresponding oligopolymer by lactic acid alcohol acid condensation polymerizations such as (and/or oxyacetic acids), oligopolymer obtains crude lactide (and/or thick glycollide through the high temperature depolymerization, and/or thick second rac-Lactide), crude lactide (and/or thick glycollide, and/or thick second rac-Lactide) obtains pure rac-Lactide (and/or pure glycollide through means such as recrystallization or distillations, and/or pure second rac-Lactide), pure rac-Lactide (and/or pure glycollide, and/or pure second rac-Lactide) (US 5023349 to obtain polylactic acid base polymer through ring-opening polymerization again, US 5374743, and US 5142023, and US 5247058, US 5247059, US5258488, US 5274073, and US 5357035, US 5484881, US 6326458, US6376643, and US 6007565, US 6004573, US 5952405, and 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 polymer, thereby is present most important preparation method, has built up the production line of producing 160000 tons of poly(lactic acid) per year as U.S. Cargill-Dow company.But because the two step method production technique is tediously long, the productive rate of particularly synthetic lactide monomers is low and have problems such as high temperature, high vacuum, high energy consumption, facility investment are big, make polylactic acid base polymer cost an arm and a leg, be difficult to and the general-purpose plastics competition, limited its application and development.
The direct polymerization rule is a starting raw material with lactic acid alcohol acids such as (and/or oxyacetic acids) directly, and the dehydrating condensation polyreaction between hydroxyl and carboxyl functional group prepares polylactic acid base polymer.Thisly often be called hydroxylated acid condensation polymer through the polymkeric substance that condensation polymerization makes by alcohol acid.The condensation polymerization of alcohol acid adopts so-called melt phase polycondensation technology usually, and promptly alcohol acid elder generation dehydrating condensation under normal pressure or low vacuum obtains oligopolymer, carries out condensation polymerization again under molten state and condition of high vacuum degree, obtains hydroxylated acid condensation polymer.Since lactic acid, oxyacetic acid source abundance, low price, and also melt phase polycondensation technology is simple, and facility investment is low, can reduce the cost of poly(lactic acid) greatly.But the heterogeneous equilibrium owing to existing in the alcohol acid melt phase polycondensation system between free hydroxyl group acid, water, polymkeric substance and the lactide often is difficult to obtain high molecular weight polymers (US 5543494, US5075115 etc.), and this is its weak point.Therefore, how melt phase polycondensation is improved polylactic acid base polymer with the synthetic macromolecule amount, be the research focus in this field always.
Nineteen ninety-five, Mitsui east pressure company has successfully developed the solution polycondensation technology (US 5770683, and US 5310865, and US 5428126, and US 5440005, and US 5444143) of using high boiling solvent, has obtained molecular weight and has been up to 300,000 poly(lactic acid).Domestic investigator has also carried out research to solution polycondensation, obtains molecular weight near 100,000 poly(lactic acid) (CN 1446836A, CN 1298892A).Solution polycondensation has increased separated from solvent and recovery process owing to use high boiling solvent, has brought problem of environmental pollution, has improved production cost, and residual in the polymkeric substance high boiling solvent is arranged, and has influenced the quality of polymkeric substance.
Publication number is that the Chinese patent of CN 1326997A discloses a kind of method that adopts dewatering agent promotion condensation polymerization to prepare polyphosphazene polymer lactic acid, obtain the poly(lactic acid) of molecular-weight average 10,000～500,000, but exist long, dewatering agent consumption of reaction times big and separate that trouble, plant factor are low, complex operation thereby cost be than problems such as height.
Publication number has been for CN 1557853A discloses the method that a kind of fusion/process for solid state polycondensation directly prepares poly(lactic acid), obtain weight-average molecular weight and be 100,000～600,000 poly(lactic acid), but the reaction times is long partially.
Though the technologic improvement of above-mentioned condensation polymerization can improve the molecular weight of polymkeric substance, but still has obvious defects.The problems such as, complex operation low, long reaction time, cost height except that aforesaid separated from solvent and recovery, dissolvent residual, environmental pollution, plant factor, these condensation polymerization technologies all adopt the catalyzer of containing metal element, this has brought another very important problem about catalyzer, promptly (1) catalyzer in acid reactants such as lactic acid, oxyacetic acid easily inactivation, (2) catalyzer to dissolve difficulties in dispersion, (3) metal catalyst in reactant residual thereby influence the biocompatibility and the electrical property of product in the resulting polymers product.Problem (1) and (2) influence preparation method's high efficiency, and problem (3) influences the purity and the quality of product, and division is as follows.
The alcohol acid condensation polymerization is used tin class, zinc class catalyzer always, as metal or organo-metallic catalysts such as tin protochloride, stannous octoate, zinc powder, zinc oxide.The catalyzer of these containing metal elements if directly join in the stronger reactant of these acidity, does not then have due katalysis owing to easy inactivation in acid reactants such as lactic acid, oxyacetic acid.Therefore, often add catalyzer again behind the alcoholic acid oligomer of earlier synthetic certain molecular weight, because oligopolymer acidity descends greatly thereby the stability problem of catalyzer is resolved, but then, because the solvability of catalyzer (as zinc powder, glass putty, tin protoxide, zinc oxide) in alcoholic acid oligomer of this class containing metal element is often relatively poor and alcoholic acid oligomer viscosity is big, catalyzer is difficult to dissolve well and disperse in alcoholic acid oligomer, therefore also has influence on catalytic effect.In addition, finish the catalyst residue of these containing metal elements of back in polymeric articles in polycondensation, the performance of impact polymer not only, as electrical property and degradation property, more the biocompatibility to polymkeric substance has a negative impact, even to the stannous octoate that authenticates by FDA (Food and Drug Adminstration) (FDA) also is so, thereby as bio-medical material the time, still have certain potential safety hazard.The residual problem of this metal catalyst not only exists in the polymkeric substance that direct polycondensation method obtains, and too so (often adopts the catalyzer of containing metal elements such as stannous octoate, tin protochloride, zinc powder, aluminium isopropoxide in as ring-opening polymerization) in the polymkeric substance that the ring-opening polymerization method obtains.Because removing residual catalyzer not only exists technical difficulty, and with high costs, therefore in industrial production, generally do not wish to remove the aftertreatment of catalyzer.
Therefore, research and development adopt containing metal element not, stablize, have efficient, low-cost, the hydroxylated acid condensation polymer that free of contamination direct polymerization method prepares high molecular, high purity (not containing the kish element) of the catalyzer of good dissolution dispersity in sour environment, and remaining in the hydroxylated acid condensation polymer research and development has technical problem to be solved.
Summary of the invention
The invention provides a kind of direct polymerization method of preparation hydroxylated acid condensation polymer of efficient, low-cost, the non-environmental-pollution that adopts efficient, non-toxic catalyst, can prepare the hydroxylated acid condensation polymer of high molecular, high purity (not containing metal element) by this method.
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 5000～100000 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 50000～200000 hydroxylated acid condensation polymer.
Alcohol acid described in the present invention 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.
The ionic liquid of the not containing metal element described in the present invention 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, m=1 or 2 in the formula, 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.
Catalyzer described in the present invention is a kind of ionic liquid or several ion liquid mixture.
Catalyzer described in the present invention is ionic liquid and nonionic mixtures of liquids, and 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.
The mass ratio of the mixture of the molar weight of catalyzer of the present invention and alcohol acid or alcoholic acid oligomer or alcohol acid and alcoholic acid oligomer is 0.001～0.2mol: 100g.
Melt condensation polymerization reaction described in the present invention is carried out according to the following steps: the mixed that catalyzer, alcohol acid are pressed 0.001～0.2mol: 100g is even, 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.
The reaction of melt condensation polymerization described in the present invention is carried 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.
Fusion described in the present invention/solid phase condensation polyreaction is carried out according to the following steps: above-mentioned weight-average molecular weight is 5000～100000 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 50000～200000 hydroxylated acid condensation polymer.
The inventive method uses the ionic liquid of containing metal element not as catalyzer, the metal remained catalyzer is to the influence of gained poly(lactic acid) biocompatibility and electrical property when having avoided common use containing metal catalyzer, and the gained poly(lactic acid) has the advantage of purity height, noresidue metal catalyst; The inventive method adopts melt phase polycondensation and fusion/solid phase polycondensation method one-step synthesis poly(lactic acid), has that technology is simple, efficient is high, cost is low, the superiority of non-environmental-pollution.Gained poly(lactic acid) of the present invention has good biocompatibility, Bioabsorbable and biodegradable, also have advantages such as molecular weight is big, mechanical property is high, easy processing simultaneously, therefore not only can be used for fields such as daily plastic, textile fibres, and can be used as bio-medical material, be used as slow releasing carrier of medication, surgery embedded material and tissue engineering bracket material etc.
The inventive method since the ionic liquid that adopts " green " as the catalyst condensation polymerization; the poly(lactic acid) that obtains also is a Biodegradable material; it is the combination of the polymkeric substance of the polymerization process of a kind of " green " and " green "; today in that environmental problem and energy dilemma become increasingly conspicuous, have great importance.
Among the present invention, both can adopt single ionic liquid, and also can adopt two kinds or two kinds of ion liquid mixtures as catalyzer as catalyzer.
Among the present invention, described contain at least a kind of molar weight of ion liquid catalyzer with as the alcohol acid of start material or the preferred 0.005mol/100g～0.05mol/100g of ratio of alcoholic acid oligomer quality.
Catalyzer with the compound use of ionic liquid among the present invention preferentially is selected from Phenylsulfonic acid and p-methyl benzenesulfonic acid.
Among the present invention, it is stable that described ionic liquid all can keep in the weak acid environment of alcohol acid reactant, can not decompose, thereby can directly join in the alcohol acid, promptly play katalysis in the water smoking, the catalyzer that has solved containing metal element commonly used is because of easy inactivation in stronger sour environment thereby can not directly not join defective in the alcohol acid reactant, has improved the catalytic effect of catalyzer.
Among the present invention, described ionic liquid is easy to dissolving, disperses in alcohol acid or alcoholic acid oligomer, catalyzer (as glass putty, zinc powder, tin protoxide, the zinc oxide) indissoluble that has overcome common containing metal element is separated, difficult dispersive shortcoming, thereby has further improved the catalytic effect of catalyzer.
Among the present invention, described ionic liquid is owing to have advantages of excellent stability and dissolution dispersity, thereby both can in the lactic acid monomer or the lactic acid monomer aqueous solution, directly add, also can add again by first synthesizing lactic acid oligopolymer, two kinds of adding modes all have good catalytic effect, have improved the elasticity of technological operation.
Among the present invention, described ionic liquid is synthetic simple, and raw material is easy to get, and most of existing commodity or reagent sells, and its synthetic method is referring to open source literature, as CN 1521163A, and CN 1417407A.
Among the present invention, the start material 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, preferred 1000～7000.
Among the present invention, lactic acid oligomer adopts conventional dehydration polycondensation method preparation by lactic acid or lactic acid aqueous solution.Can not add catalyzer in the oligopolymer preparation process, also can add and of the present inventionly contain a kind of ion liquid catalyzer at least, but not add the catalyzer of the containing metal element of common employing.
The present invention is that the condensation polymerization method of Preparation of Catalyst hydroxylated acid condensation polymer both can adopt melt polycondensation method with the ionic liquid, also can proceed solid phase polycondensation behind melt polymerization, i.e. fusion/method for solid phase polymerization is with the molecular weight of further raising poly(lactic acid).
Among the present invention, preferred 110 ℃～150 ℃ of the temperature of preparation alcoholic acid oligomer, the preferred 1000Pa of pressure～1.013 * 10
5Pa.
Among the present invention, preferred 150 ℃～185 ℃ of the temperature in melt phase polycondensation stage, the preferred 100Pa～500Pa of pressure.
Among the present invention, preferred 100 ℃～170 ℃ of the temperature in solid phase polycondensation stage, when leading to protection of inert gas, pressure preferred 1.013 * 10
5Pa～1.5 * 10
5Pa vacuumizes the preferred 1Pa～200Pa of pressure when carrying out solid phase polycondensation.
It is 5000～200000 hydroxylated acid condensation polymer that method provided by the invention can be synthesized weight-average molecular weight.The mensuration of molecular weight adopts field of polymer technology method commonly used to carry out, and measures as terminal group titration, intrinsic viscosity method and gel permeation chromatography (GPC).
Embodiment
The embodiment that the invention is further illustrated by the following examples, but scope of the present invention is not limited to these embodiment.
Embodiment 1
The L-lactic acid aqueous solution of 50 grams 90% is joined in the 250mL three neck round-bottomed flasks, start magnetic agitation, the oil bath heating.Dehydration is 2 hours under 100 ℃, normal pressure; Gradually pressure is reduced to 1300Pa (10 mmhg) then, temperature is elevated to 130 ℃, dewatered 2 hours; Obtain weight-average molecular weight and be 520 L-lactic acid oligomer; Then continue dehydration 4 hours down, obtain weight-average molecular weight and be 1610 lactic acid oligomer at 150 ℃, 520Pa (4 mmhg).After the cooling, 0.002 mole first base, three phenyl phosphonium bromides are added in the three neck round-bottomed flasks, mix, progressively temperature is elevated to 170 ℃, gradually pressure is reduced to 130Pa (1 mmhg), reacted 10 hours, the productive rate of poly(lactic acid) is 90.5%, recording weight-average molecular weight by gel permeation chromatography is 12870, and polydispersity index is 1.36.
Embodiment 2
The preparation of lactic acid oligomer such as embodiment 1.The tetrabutylammonium chloride that in the lactic acid oligomer of gained, adds 0.002 mole, progressively be warming up to 170 ℃, the 130Pa (1 mmhg) that reduces pressure progressively, reacted 10 hours, the productive rate of poly(lactic acid) is 84.7%, recording weight-average molecular weight by gel permeation chromatography is 6870, and polydispersity index is 1.48.
Embodiment 3
The preparation of lactic acid oligomer such as embodiment 1.The N-butyl-pyridinium bromide that in the lactic acid oligomer of gained, adds 0.004 mole, progressively be warming up to 170 ℃, the 130Pa (1 mmhg) that reduces pressure progressively, reacted 10 hours, the productive rate of poly(lactic acid) is 93.1%, recording weight-average molecular weight by gel permeation chromatography is 11000, and polydispersity index is 1.26.
Embodiment 4
The preparation of lactic acid oligomer such as embodiment 1.1-butyl-3-Methylimidazole the bromide (bmimBr) that in the lactic acid oligomer of gained, adds 0.005 mole, progressively be warming up to 190 ℃, the 130Pa (1 mmhg) that reduces pressure progressively, reacted 10 hours, the productive rate of poly(lactic acid) is 84.2%, recording weight-average molecular weight by gel permeation chromatography is 9610, and polydispersity index is 1.44.
Embodiment 5
With the L-lactic acid aqueous solution of 50 grams 90% and 1-ethyl-3-Methylimidazole hexafluorophosphate (emimPF of 0.0025 mole
6) add in three mouthfuls of round-bottomed flasks of 250mL, start magnetic agitation, the oil bath heating.Reaction is 3 hours under 110 ℃, normal pressure, gradually pressure is reduced to 1330Pa (10 mmhg) then, temperature is elevated to 130 ℃, reacted 3 hours, then in the reaction 5 hours down of 150 ℃, 130Pa (1 mmhg), again in the reaction 13 hours down of 170 ℃, 130Pa (1 mmhg).The productive rate of poly(lactic acid) is 83.4%, and recording weight-average molecular weight by gel permeation chromatography is 5970, and polydispersity index is 1.39.
Embodiment 6
The L-lactic acid aqueous solution of 50 grams 90% is added in the 250mL three neck round-bottomed flasks, start magnetic agitation, the oil bath heating.Dehydration is 2 hours under 110 ℃, normal pressure; Gradually pressure is reduced to 1330Pa (10 mmhg) then, temperature is elevated to 130 ℃, dewatered 2 hours; Then continue dehydration 4 hours down at 150 ℃, 520Pa (4 mmhg); Dehydration 10 hours under 170 ℃, 100Pa again obtains weight-average molecular weight and is 7360 L-lactic acid oligomer.The reaction 20 hours down of the 1-butyl-3-Methylimidazole muriate (bmimCl) that adds 0.002 mole, 170 ℃, 133Pa, the productive rate of poly(lactic acid) is 88.1%, and recording weight-average molecular weight by gel permeation chromatography is 28860, and polydispersity index is 1.32.
Embodiment 7
The preparation of lactic acid oligomer such as embodiment 1.After the cooling, in flask, add 1-butyl-3-Methylimidazole trifluoroacetate of 0.002 mole, progressively be warming up to 170 ℃, progressively reduce pressure 10
3Pa reacted 10 hours.The productive rate of poly(lactic acid) is 68.8%, and recording weight-average molecular weight by gel permeation chromatography is 17310, and polydispersity index is 1.63.
Embodiment 8
The preparation of lactic acid oligomer such as embodiment 1.1-ethyl-3-Methylimidazole the bromide (emimBr) that adds 0.002 mole in the lactic acid oligomer of gained progressively is warming up to 170 ℃, the 133Pa (1 mmhg) that reduces pressure progressively, reacts 10 hours; 1-butyl-3-Methylimidazole the muriate (bmimCl) that adds 0.004 mole after the cooling more progressively is warming up to 180 ℃, the 70Pa (0.5 mmhg) that reduces pressure progressively, reacts 20 hours.The productive rate of poly(lactic acid) is 80.4%, and recording weight-average molecular weight by gel permeation chromatography is 32638, and polydispersity index is 1.23.
Embodiment 9
The preparation of lactic acid oligomer such as embodiment 1.In the lactic acid oligomer of gained, add 0.002 mole 1, the 1-butyl-3-Methylimidazole acetate (bmimCOOCH of 3-dibutyl imidazoles L-lactic acid salt and 0.002 mole
3), progressively be warming up to 170 ℃, the 130Pa that reduces pressure progressively, reacted 10 hours.The productive rate of poly(lactic acid) is 94.0%, and recording weight-average molecular weight by gel permeation chromatography is 29350, and polydispersity index is 1.35.
Embodiment 10
The preparation of lactic acid oligomer such as embodiment 1.1-hexyl-3-Methylimidazole acetate (the hmimCOOCH that in the lactic acid oligomer of gained, adds 0.08 mole
3), progressively be warming up to 170 ℃, the 133Pa that reduces pressure progressively, reacted 10 hours.The productive rate of poly(lactic acid) is 81.4%, and recording weight-average molecular weight by gel permeation chromatography is 19306, and polydispersity index is 1.33.
Embodiment 11
The preparation of lactic acid oligomer such as embodiment 1.The 1-ethyl-2 that adds 0.001 mole in the lactic acid oligomer of gained, the silicon-dioxide of 3-methylimidazole perfluoro butyrate and 0.005 mole progressively is warming up to 170 ℃, the 133Pa that reduces pressure progressively, reacts 15 hours.The productive rate of poly(lactic acid) is 83.6%, and recording weight-average molecular weight by gel permeation chromatography is 16420, and polydispersity index is 1.66.
Embodiment 12
With the D of 50 grams 90%, the L-lactic acid aqueous solution adds in the 250mL three neck round-bottomed flasks, starts magnetic agitation, the oil bath heating.Dehydration is 2 hours under 110 ℃, normal pressure; Gradually pressure is reduced to 1330Pa (10 mmhg) then, temperature is elevated to 130 ℃, dewatered 2 hours; Then continue dehydration 4 hours down at 150 ℃, 520Pa (4 mmhg).1-ethyl-3-Methylimidazole the D that adds 0.005 mole, the L-lactic acid salt progressively is warming up to 170 ℃, the 133Pa that reduces pressure progressively, reacted 20 hours, the productive rate of poly(lactic acid) is 84.5%, and recording weight-average molecular weight by gel permeation chromatography is 25950, and polydispersity index is 1.48.
Embodiment 13
The preparation of lactic acid oligomer such as embodiment 1.In the lactic acid oligomer of gained, add 0.002 mole 1, the p-methyl benzenesulfonic acid of 3-diethyl imidazoles L-lactic acid salt and 0.0002 mole progressively is warming up to 170 ℃, the 130Pa that reduces pressure progressively, reacts 10 hours.Continue to be warming up to 180 ℃, the 70Pa (0.5 mmhg) that reduces pressure progressively, reacted 20 hours, the productive rate of poly(lactic acid) is 82.1%, and recording weight-average molecular weight by gel permeation chromatography is 33140, and polydispersity index is 1.37.
Embodiment 14
The preparation of lactic acid oligomer such as embodiment 1.In the lactic acid oligomer of gained, add 0.004 mole 1,3-diethyl imidazoles L-lactic acid salt progressively is warming up to 170 ℃, the 130Pa that reduces pressure progressively, reacts 10 hours.Then be warming up to 180 ℃, the 1Pa that reduces pressure progressively, reacted 48 hours, the productive rate of poly(lactic acid) is 79.2%, and recording weight-average molecular weight by gel permeation chromatography is 46310, and polydispersity index is 1.53.
Embodiment 15
The preparation of lactic acid oligomer such as embodiment 1.In the lactic acid oligomer of gained, in flask, add 0.002 mole 1, the Phenylsulfonic acid of 3-diethyl imidazoles L-lactic acid salt and equimolar amount, progressively be warming up to 170 ℃, the 400Pa (3 mmhg) that reduces pressure progressively, reacted 10 hours, then progressively be warming up to 180 ℃, the 260Pa (2 mmhg) that progressively reduces pressure reacted 20 hours, obtained weight-average molecular weight and be 39200 poly(lactic acid).The cooling back is taken out and is pulverized, screening is the crystallization 2 hours under 105 ℃, 130Pa of the poly(lactic acid) particle of 5mm with the particle diameter that obtains, and progressively is warmed up to 150 ℃ then, the 70Pa (0.5 mmhg) that reduces pressure reacts that to obtain weight-average molecular weight after 5 hours be 43400 poly(lactic acid); Then progressively be warmed up to 160 ℃, the 10Pa that reduces pressure obtains weight-average molecular weight and is 53900 poly(lactic acid) after 10 hours, obtains weight-average molecular weight after 20 hours and be 66640 poly(lactic acid); Continue progressively to be warmed up to 1670 ℃, the 1Pa that reduces pressure obtains weight-average molecular weight and is 78800 poly(lactic acid) after 20 hours, obtains weight-average molecular weight after 30 hours and be 89630 poly(lactic acid).
Embodiment 16
The preparation of lactic acid oligomer such as embodiment 1.1-ethyl-3-Methylimidazole acetate (the emimCOOCH that in the lactic acid oligomer of gained, adds 0.004 mole
3) and the p-methyl benzenesulfonic acid (TSA) of equimolar amount, progressively be warming up to 170 ℃, the 260Pa (2 mmhg) that reduces pressure progressively, reacted 20 hours, then progressively be warming up to 180 ℃, the 130Pa that progressively reduces pressure reacted 48 hours, obtained weight-average molecular weight and be 89300 poly(lactic acid).Cooling back is taken out and is pulverized, and screening is that the poly(lactic acid) particulate of 10 μ m is packed in the three-necked flask logical continuously N into the particle diameter that obtains
2Protection makes pressure remain on 2 * 10
5Pa progressively is warmed up to 105 ℃, crystallization 2 hours; Then be warmed up to 120 ℃, crystallization 4 hours; Be warming up to 135 ℃ again, crystallization 4 hours; Progressively be warmed up to 150 ℃, react that to obtain weight-average molecular weight after 15 hours be 115200 poly(lactic acid), obtain weight-average molecular weight after 25 hours and be 136600 poly(lactic acid), obtain weight-average molecular weight after 35 hours and be 162400 poly(lactic acid), obtain weight-average molecular weight after 45 hours and be 175000 poly(lactic acid), obtain weight-average molecular weight after 60 hours and be 184700 poly(lactic acid).
Embodiment 17
20 gram oxyacetic acids are added in the 100mL three neck round-bottomed flasks, start magnetic agitation, the oil bath heating.Dehydration is 2 hours under 110 ℃, normal pressure, gradually pressure is reduced to 1300Pa (10 mmhg) then, and temperature is elevated to 130 ℃, dewater 2 hours, then continues to dewater 4 hours under 150 ℃, 130Pa.1-butyl-3-Methylimidazole the muriate (bmimCl) that adds 0.04 mole progressively is warming up to 170 ℃, the 540Pa that reduces pressure progressively, reacts 10 hours, then progressively is warming up to 180 ℃, the 130Pa that reduces pressure progressively, reacts 10 hours.Take out the cooling back.Because the PGA that direct polycondensation method obtains is insoluble to common organic solvent, the undetermined molecular weight.
Embodiment 18
5 gram oxyacetic acids and 20 gram lactic acid are joined in the 100mL three neck round-bottomed flasks, add 1-butyl-3-Methylimidazole muriate (bmimCl) of 0.003 mole then.Start magnetic agitation, the oil bath heating.Reaction is 2 hours under 110 ℃, normal pressure; Gradually pressure is reduced to 1300Pa then, temperature is elevated to 130 ℃, reacted 2 hours; Then under 150 ℃, 520Pa, continue reaction 4 hours.Progressively be warming up to 170 ℃, the 260Pa (2 mmhg) that reduces pressure progressively then, reacted 10 hours, then progressively be warming up to 180 ℃, the 130Pa that reduces pressure progressively, reacted 10 hours.The productive rate of PLGA is 83.9%, and recording weight-average molecular weight by gel permeation chromatography is 26410, and 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.
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| CN101896467A (en) * | 2007-12-12 | 2010-11-24 | 巴斯夫欧洲公司 | Method for the production of disubstituted imidazolium salts |
| CN101747501B (en) * | 2008-12-12 | 2011-10-26 | 北京服装学院 | Method for synthesizing high molecular weight polylactic acid |
| CN102627756A (en) * | 2012-03-28 | 2012-08-08 | 南京工业大学 | Synthetic method of polylactic acid-polyethylene glycol |
| CN102633996B (en) * | 2012-05-10 | 2014-01-01 | 南京工业大学 | Method for catalytically synthesizing polylactic acid by using ionic liquid |
| CN103265688B (en) * | 2013-06-13 | 2015-03-04 | 武汉大学 | Preparation method of glycolic acid polymer |
| CN107177032B (en) * | 2016-03-11 | 2019-04-02 | 上海浦景化工技术股份有限公司 | By the method for glycolic or methyl glycollate preparation high molecular weight polyglycolic acid |
| CN105646441A (en) * | 2016-03-11 | 2016-06-08 | 东华大学 | Method for preparing lactide |
| CN106432698B (en) * | 2016-10-17 | 2019-02-26 | 杭州铭众生物科技有限公司 | The method that hydroxyacetic acid polymerization prepares polyglycolic acid |
| CN109535406B (en) * | 2017-09-22 | 2021-07-30 | 宁波聚嘉新材料科技有限公司 | Preparation method of polyarylate based on 2- (3-hydroxyphenyl) -6-carboxypyridoimidazole |
| CN112280021B (en) * | 2020-09-25 | 2022-09-06 | 内蒙古久泰新材料有限公司 | Method for preparing polyglycolic acid |
| CN114957196B (en) * | 2022-05-06 | 2023-11-14 | 哈尔滨工业大学（威海） | Method for synthesizing diester-based cyclic ester by catalysis of ionic liquid analogue |
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| US5543494A (en) * | 1992-08-04 | 1996-08-06 | Ministero Dell'univerita' E Della Ricerca Scientifica E Tecnologica | Process for the production of poly(lactic acid) |
| CN1557853A (en) * | 2004-02-05 | 2004-12-29 | 哈尔滨工业大学 | Process for direct preparation of poly-lactic acid from lactic acid by melt/solid phase polycondensation |
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| 熔融缩聚法制备聚乳酸 任杰 王秦峰 张乃文，塑料工业，第32卷第5期 2004 * |
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