CN110117359B - Polyether-b-poly (gamma-butyrolactone) block copolymer and preparation method thereof - Google Patents
Polyether-b-poly (gamma-butyrolactone) block copolymer and preparation method thereof Download PDFInfo
- Publication number
- CN110117359B CN110117359B CN201810109765.7A CN201810109765A CN110117359B CN 110117359 B CN110117359 B CN 110117359B CN 201810109765 A CN201810109765 A CN 201810109765A CN 110117359 B CN110117359 B CN 110117359B
- Authority
- CN
- China
- Prior art keywords
- butyrolactone
- compound
- alkali metal
- gamma
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/66—Polyesters containing oxygen in the form of ether groups
- C08G63/664—Polyesters containing oxygen in the form of ether groups derived from hydroxy carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/332—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/332—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof
- C08G65/3322—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof acyclic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/34—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from hydroxy compounds or their metallic derivatives
- C08G65/48—Polymers modified by chemical after-treatment
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Polyethers (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a compound and a preparation method thereof. The compound is a compound shown in a formula (I) or a stereoisomer, a geometric isomer, a tautomer, a nitrogen oxide, a hydrate or a solvate of the compound shown in the formula (I). The invention obtains the amphiphilic polyether-b-poly (gamma-butyrolactone) block copolymer for the first time, and is expected to have great application prospect in the biomedical fields of drug delivery, tissue engineering repair and the like. Compared with the prior polyether-b-polyester system, the polyether-b-poly (gamma-butyrolactone) block copolymer has more proper degradation rate in vivo, is not easy to cause inflammation in vivo, and is a more ideal medical biomaterial.
Description
Technical Field
The invention relates to the field of chemical industry. In particular, the present invention relates to polyether-b-poly (gamma-butyrolactone) block copolymers and methods for their preparation.
Background
The amphiphilic block copolymer is an important high molecular material, can be self-assembled in an aqueous solution to form micelles, vesicles or hydrogel, and has important applications in the biomedical field, including drug delivery, gene transfection, tissue engineering repair and the like. Among them, polyethylene oxide (PEG) is often used as the hydrophilic segment therein. PEG has been approved by the U.S. Food and Drug Administration (FDA) for clinical use. The PEG-coated drug can remarkably prolong the circulation time of the drug in blood and simultaneously reduce the endocytosis of an immune system. The aliphatic polyester has good biocompatibility and biodegradability, low immunogenicity and good mechanical properties, and is an ideal choice for the hydrophobic chain segment.
However, at present, polyethylene oxide-aliphatic polyester block copolymers still remain to be developed.
Disclosure of Invention
The present invention aims to solve at least one of the problems of the prior art to at least some extent.
It should be noted that the present invention has been completed based on the following findings of the inventors:
poly (gamma-butyrolactone) is an important class of aliphatic polyesters with the following advantages: the gamma-butyrolactone can be prepared from succinic acid, and has wide source and low price. Succinic acid can be obtained from biomass raw materials, such as corn, wheat and other crops, and is a renewable raw material. Poly (gamma-butyrolactone) has a proper degradation rate in vivo, which is between that of polyglycolide and polylactic acid, but unlike polyglycolide and polylactic acid, poly (gamma-butyrolactone) does not cause accumulation of acidic substances in tissues during degradation, and is not easy to cause inflammation, so that it is particularly suitable for the biomedical field. Currently, poly (gamma-butyrolactone) has been FDA approved for clinical use as a surgical suture and hernia patch.
However, gamma-butyrolactone has a five-membered ring structure, has a small ring tension, and it is difficult to obtain poly (gamma-butyrolactone) having a high molecular weight by a ring-opening polymerization method. The poly (gamma-butyrolactone) commercially used at present is mainly obtained by a biological fermentation method, which results in difficulty in preparing a copolymer of gamma-butyrolactone with a complex structure and other monomers by a chemical modification method.
In view of the above, the inventors tried to use hydroxyl-terminated polyether as macroinitiator, and under the catalytic action of catalyst or alkali metal compound or alkali metal alkoxy compound, by screening suitable reaction conditions, successfully obtain polyether-b-poly (gamma-butyrolactone) block copolymer at low temperature. Particularly, the low-temperature condition can effectively reduce the influence of the system entropy effect in the polymerization process, and is an important condition for ensuring the success of polymerization. The invention obtains the amphiphilic polyether-b-poly (gamma-butyrolactone) block copolymer for the first time, and is expected to have great application prospect in the biomedical fields of drug delivery, tissue engineering repair and the like. Compared with the prior polyether-b-polyester system, the polyether-b-poly (gamma-butyrolactone) block copolymer has more proper degradation rate in vivo, is not easy to cause inflammation in vivo, and is a more ideal medical biomaterial.
To this end, in one aspect of the invention, the invention provides a compound. According to an embodiment of the invention, the compound is a compound of formula (I) or a stereoisomer, a geometric isomer, a tautomer, a nitrogen oxide, a hydrate or a solvate of a compound of formula (I),
wherein the content of the first and second substances,
r is selected from alkyl, alkenyl, alkynyl, alkoxy, alkylamino, cycloalkyl, heterocyclic group, aryl, heteroaryl, fused bicyclic group, spiro bicyclic group, fused heterobicyclic group, spiro heterobicyclic group or a group shown in formula (II),
R1a group selected from hydrogen or one of the following:
R2a group selected from one of the following:
R3and R4Each independently selected from alkyl, alkenyl, alkoxy, alkylamino, cycloalkyl, heterocyclyl, aryl or heteroaryl,
x, y and n are each independently selected from natural numbers of not less than 5.
The compounds of the present invention are block copolymers formed from polyethers and poly (gamma-butyrolactone). The block copolymer is initiated by hydroxyl-terminated polyether, and when the hydroxyl-terminated polyether is single-terminal hydroxyl, polyether-b-poly (gamma-butyrolactone) two-block copolymer is obtained; when the hydroxyl-terminated polyether is a double-end hydroxyl, the poly (gamma-butyrolactone) -b-polyether-b-poly (gamma-butyrolactone) triblock copolymer is formed by left-right symmetry with the polyether as an axis. The invention obtains the amphiphilic polyether-b-poly (gamma-butyrolactone) block copolymer for the first time, and is expected to have great application prospect in the biomedical fields of drug delivery, tissue engineering repair and the like. Compared with the prior polyether-b-polyester system, the polyether-b-poly (gamma-butyrolactone) block copolymer has more proper degradation rate in vivo, is not easy to cause inflammation in vivo, and is a more ideal medical biomaterial.
According to an embodiment of the invention, the above-mentioned compounds may also have the following additional technical features:
according to an embodiment of the invention, R3And R4Each independently selected from one of the following:
according to an embodiment of the invention, the compound has the structure of one of the following:
wherein each R is5Each independently selected from hydrogen, methyl or ethyl.
According to an embodiment of the invention, the compound has the structure of one of the following:
in another aspect of the invention, the invention provides a process for preparing the aforementioned compound. According to an embodiment of the invention, the method comprises:
(1) dissolving a catalyst or an alkali metal compound or an alkali metal alkoxy compound and hydroxyl-terminated polyether in an organic solvent to obtain a mixed solution;
(2) mixing gamma-butyrolactone with the mixed solution, carrying out a reaction, adding a compound containing an active functional group to terminate the reaction, adding the reaction mixture to methanol, and collecting the precipitate, so as to obtain the compound, wherein the reaction is carried out at-70 to-20 ℃.
The inventor tries to successfully obtain the polyether-b-poly (gamma-butyrolactone) diblock copolymer at low temperature (-70 to-20 ℃) by using hydroxyl-terminated polyether as a macroinitiator and screening proper reaction conditions under the catalysis of a catalyst or an alkali metal compound or an alkali metal alkoxy compound. Particularly, the low-temperature condition can effectively reduce the influence of the system entropy effect in the polymerization process, and is an important condition for ensuring the success of polymerization. The method has the advantages of high yield, high product purity, simple operation and suitability for large-scale production. Meanwhile, the invention obtains the amphiphilic polyether-b-poly (gamma-butyrolactone) block copolymer for the first time, and is expected to have great application prospect in the biomedical fields of drug delivery, tissue engineering repair and the like. Compared with the prior polyether-b-polyester system, the polyether-b-poly (gamma-butyrolactone) block copolymer has more proper degradation rate in vivo, is not easy to cause inflammation in vivo, and is a more ideal medical biomaterial.
According to an embodiment of the invention, the catalyst is selected from an organophosphazene base catalyst, preferably hexa [ tris (dimethylamine) phosphazene ] triphosphazene, phosphazene ligand P4-tert-butyl or phosphazene ligand P2-tert-butyl. The inventor finds that the compound obtained under the condition has high yield and good purity through a large number of experiments.
According to an embodiment of the invention, the alkali metal is selected from sodium or potassium and the alkali metal compound is selected from sodium hydride, potassium hydride, sodium naphthalene, potassium naphthalene, sodium biphenyl, sodium diphenylmethyl or potassium diphenylmethyl. The inventor finds that the compound obtained under the condition has high yield and good purity through a large number of experiments.
According to an embodiment of the invention, the alkali metal alkoxide is selected from potassium methoxide, sodium ethoxide or potassium ethoxide. The inventor finds that the compound obtained under the condition has high yield and good purity through a large number of experiments.
According to an embodiment of the invention, the hydroxyl terminated polyether is selected from polyethylene oxide monomethyl ether, polypropylene oxide monomethyl ether, poly (1, 2-butylene oxide) monomethyl ether, polyethylene oxide, polypropylene oxide, poly (1, 2-butylene oxide), polyethylene oxide-b-polypropylene oxide-b-polyethylene oxide or poly (ethylene oxide-ran-propylene oxide). The inventor finds that the compound obtained under the condition has high yield and good purity through a large number of experiments.
According to an embodiment of the invention, the reactive functional group containing compound is selected from the group consisting of acids, acid chlorides, acid anhydrides, thioisocyanates, isocyanates or halogenated hydrocarbons, preferably acetic acid, benzoic acid, acryloyl chloride, methacryloyl chloride, acetic anhydride, succinic anhydride, maleimidobutyryl chloride, epichlorohydrin, 3-chloropropene, 3-chloropropyne, 4-methoxyphenyl thioisocyanate, 4-methoxyphenyl isocyanate. The inventor finds that the compound obtained under the condition has high yield and good purity through a large number of experiments.
According to an embodiment of the invention, the method comprises: (1-1) dissolving hydroxyl-terminated polyether and a catalyst in an organic solvent, and stirring in a low-temperature cold bath; (1-2) adding gamma-butyrolactone to the mixed solution obtained in the step (1-1), reacting, adding a compound containing a reactive functional group to terminate the reaction, adding the reaction mixture to methanol, and collecting the precipitate, to obtain the compound, wherein the molar ratio of the catalyst to the hydroxyl-terminated polyether is 1: 3-2: 1; the organic solvent is at least one selected from tetrahydrofuran, dichloromethane, trichloromethane, 1-dichloroethane, 1, 2-dichloroethane, 1,2, 2-tetrachloroethane, acetonitrile and dioxane; the low-temperature cold bath stirring is carried out for 10-30 min at the temperature of-70 to-10 ℃. The inventor finds that the compound obtained under the condition has high yield and good purity through a large number of experiments.
According to an embodiment of the invention, the method comprises: (2-1) dissolving hydroxyl-terminated polyether and alkali metal or alkali metal compound in an organic solvent, reacting under the protection of nitrogen, and filtering to obtain polyether alkali metal salt solution; (2-2) dissolving the polyether alkali metal salt solution and gamma-butyrolactone in an organic solvent, reacting, adding a compound containing a reactive functional group to terminate the reaction, adding the reaction mixture to methanol, and collecting the precipitate, to obtain the compound, wherein the molar ratio of the hydroxyl-terminated polyether to the alkali metal or alkali metal compound is 1: 1-1: 10; in the step (2-1), the reaction temperature is 25-70 ℃, the reaction time is 0.5-72 hours, and the organic solvent is selected from tetrahydrofuran or dioxane; in the step (2-2), the organic solvent is at least one selected from the group consisting of tetrahydrofuran, dichloromethane, chloroform, 1-dichloroethane, 1, 2-dichloroethane, 1,2, 2-tetrachloroethane, acetonitrile and dioxane; the molar ratio of the polyether alkali metal salt to the gamma-butyrolactone is 1: 10-1: 200. the inventor finds that the compound obtained under the condition has high yield and good purity through a large number of experiments.
According to an embodiment of the invention, the method comprises: (3-1) dissolving hydroxyl-terminated polyether and alkali metal alkoxy compound in organic solvent, and stirring in low-temperature cold bath; (3-2) adding gamma-butyrolactone to the mixed solution obtained in the step (3-1), reacting, adding a compound having a reactive functional group to terminate the reaction, adding the reaction mixture to methanol, and collecting the precipitate, to obtain the compound, wherein the molar ratio of the alkali metal alkoxide to the hydroxyl-terminated polyether is 1: 1-2: 1; the organic solvent is at least one selected from tetrahydrofuran, dichloromethane, trichloromethane, 1-dichloroethane, 1, 2-dichloroethane, 1,2, 2-tetrachloroethane, acetonitrile and dioxane; the low-temperature cold bath stirring is carried out for 10-30 min at the temperature of-70 to-10 ℃. The inventor finds that the compound obtained under the condition has high yield and good purity through a large number of experiments.
According to the embodiment of the invention, the molecular weight of the hydroxyl-terminated polyether is 200-40000 g/mol, and the molar ratio of the hydroxyl-terminated polyether to gamma-butyrolactone is 1: 10-1: 200 of a carrier; the molar concentration of the gamma-butyrolactone in the system is 2-10 mol/L; the molar ratio of the compound containing the active functional group to the hydroxyl-terminated polyether is 1: 1-10: 1; the reaction is carried out at-70 to-20 ℃ for 0.5 to 12 hours. The inventor finds that the compound obtained under the condition has high yield and good purity through a large number of experiments.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Drawings
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
FIG. 1 is a 1H NMR spectrum of polyethylene oxide-b-poly (. gamma. -butyrolactone) obtained in example 1;
FIG. 2 is a 1H NMR spectrum of polyethylene oxide-b-poly (. gamma. -butyrolactone) obtained in example 2;
FIG. 3 is a 1H NMR spectrum of polyethylene oxide-b-poly (. gamma. -butyrolactone) obtained in example 3;
FIG. 4 is a 13C NMR spectrum of polyethylene oxide-b-poly (. gamma. -butyrolactone) obtained in example 1;
FIG. 5 is a GPC chart of polyethylene oxide-b-poly (γ -butyrolactone) prepared in example 1 with PEG 2000;
FIG. 6 is a GPC chart of polyethylene oxide-b-poly (γ -butyrolactone) prepared in example 2 with PEG 2000;
FIG. 7 is a GPC chart of polyethylene oxide-b-poly (γ -butyrolactone) prepared in example 3 with PEG 5000;
FIG. 8 is a GPC chart of polyethylene oxide-b-poly (γ -butyrolactone) prepared in example 4 with PEG 2000;
FIG. 9 is a GPC chart of polyethylene oxide-b-poly (γ -butyrolactone) prepared in example 5 with PEG 2000;
FIG. 10 is an IR spectrum of polyethylene oxide-b-poly (. gamma. -butyrolactone) prepared in example 1;
FIG. 11 is an IR spectrum of polyethylene oxide-b-poly (. gamma. -butyrolactone) obtained in example 3.
Detailed Description
The following describes embodiments of the present invention in detail. The following examples are illustrative only and are not to be construed as limiting the invention.
Definitions and general terms
In the context of the present invention, all numbers disclosed herein are approximate values. The numerical value of each number may vary by 1%, 2%, 5%, 7%, 8%, or 10%. Whenever a number is disclosed with a value of N, any number within the values of N +/-1%, N +/-2%, N +/-3%, N +/-5%, N +/-7%, N +/-8% or N +/-10% is explicitly disclosed, wherein "+/-" means plus or minus. Whenever a lower limit, DL, and an upper limit, DU, are disclosed in a range of values, any value falling within the disclosed range is expressly disclosed.
All reaction steps described in the present invention are carried out to an extent such that the consumption of the starting materials is greater than about 70%, greater than 80%, greater than 90%, greater than 95%, or the reaction starting materials are detected to have been consumed and then subjected to post-treatment such as cooling, collection, extraction, filtration, separation, purification or a combination thereof. The degree of reaction can be detected by a conventional method such as Thin Layer Chromatography (TLC), High Performance Liquid Chromatography (HPLC), Gas Chromatography (GC) and the like. The reaction solution may be worked up by a conventional method, for example, by evaporating under reduced pressure or by distilling the reaction solvent conventionally, collecting the crude product, and directly subjecting it to the next reaction; or directly filtering to obtain a crude product, and directly putting the crude product into the next reaction; or after standing, pouring out supernatant to obtain a crude product, and directly putting the crude product into the next reaction; or selecting proper organic solvent or their combination to make purification steps of extraction, distillation, crystallization, column chromatography, rinsing and pulping.
Reference will now be made in detail to certain embodiments of the invention, examples of which are illustrated by the accompanying structural and chemical formulas. The invention is intended to cover alternatives, modifications and equivalents, which may be included within the scope of the invention as defined by the appended claims. Those skilled in the art will recognize that many methods and materials similar or equivalent to those described herein can be used in the practice of the present invention. The present invention is in no way limited to the methods and materials described herein. In the event that one or more of the incorporated documents, patents, and similar materials differ or contradict this application (including but not limited to defined terminology, application of terminology, described techniques, and the like), this application controls.
It will be further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference in their entirety.
The following definitions as used herein should be applied unless otherwise indicated. For the purposes of the present invention, the chemical elements are in accordance with the CAS version of the periodic Table of the elements, and the handbook of chemistry and Physics, 75 th edition, 1994. In addition, general principles of Organic Chemistry can be referred to as described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausaltito: 1999, and "March's Advanced Organic Chemistry" by Michael B.Smith and Jerry March, John Wiley & Sons, New York:2007, the entire contents of which are incorporated herein by reference.
The term "comprising" is open-ended, i.e. comprising what is specified in the invention, but does not exclude other aspects.
"stereoisomers" refers to compounds having the same chemical structure but differing in the arrangement of atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformers (rotamers), geometric isomers (cis 20/trans), atropisomers, and the like.
The stereochemical definitions and rules used in the present invention generally follow the general definitions of S.P. Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E.and Wilen, S., "Stereochemistry of Organic Compounds", John Wiley & Sons, Inc., New York, 1994.
The term "tautomer" or "tautomeric form" refers to structural isomers having different energies that can interconvert by a low energy barrier (low energy barrier). If tautomerism is possible (e.g., in solution), then the chemical equilibrium of the tautomer can be reached. Unless otherwise indicated, all tautomeric forms of the compounds of the invention are within the scope of the invention.
"solvate" of the present invention refers to an association of one or more solvent molecules with a compound of the present invention. Solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, 25 acetic acid, aminoethanol.
"nitroxide" in the context of the present invention means that when a compound contains several amine functional groups, 1 or more than 1 nitrogen atom can be oxidized to form an N-oxide. Specific examples of N-oxides are N-oxides of tertiary amines or N-oxides of nitrogen-containing heterocyclic nitrogen atoms. The corresponding amines can be treated with an oxidizing agent such as hydrogen peroxide or a peracid (e.g., peroxycarboxylic acid) to form the N-oxide (see Advanced Organic Chemistry, Wiley Interscience, 4 th edition, Jerry March, pages).
The symbol "ran" in the structural formula of the present invention refers to a random copolymer (random copolymer), i.e., the monomers M1, M2 are randomly arranged on the macromolecular chain, the two monomers are randomly distributed on the main chain, and no one monomer can form a single longer chain segment on the molecular chain.
The term "alkyl" as used herein includes saturated straight or branched chain monovalent hydrocarbon radicals wherein the alkyl radical may independently be optionally substituted with one or more substituents as described herein. In some of these embodiments, the alkyl group contains 1 to 10 carbon atoms; in other embodiments, the alkyl group contains 1 to 8 carbon atoms; in other embodiments, the alkyl group contains 1 to 6 carbon atoms, and in other embodiments, the alkyl group contains 1 to 4 carbon atoms; in other embodiments, the alkyl group contains 1 to 3 carbon atoms. Further examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-methylpropyl or isobutyl, 1-methylpropyl or sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, n-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2, 3-dimethyl-2-butyl, 3, 3-dimethyl-2-butyl, n-heptyl, n-octyl, and the like. The term "alkyl" and its prefix "alkane" as used herein, both include straight and branched saturated carbon chains. Alkyl groups may be substituted with the substituents described herein.
The term "alkoxy", as used herein, relates to an alkyl group, as defined herein, attached to the main carbon chain through an oxygen atom. Such examples include, but are not limited to, methoxy, ethoxy, propoxy, and the like. Alkoxy groups may be substituted with the substituents described herein.
The term "cycloalkyl" or "carbocycle" refers to a mono-or polyvalent, non-aromatic, saturated or partially unsaturated ring, and does not contain heteroatoms, including monocyclic rings of 3 to 12 carbon atoms or bicyclic or tricyclic rings of 3 to 12 carbon atoms. Suitable cycloalkyl groups include, but are not limited to, cycloalkyl, cycloalkenylAnd cycloalkynyl. Examples of cycloalkyl groups further include, but are in no way limited to, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopentyl-1-alkenyl, 1-cyclopentyl-2-alkenyl, 1-cyclopentyl-3-alkenyl, cyclohexyl, 1-cyclohexyl-1-alkenyl, 1-cyclohexyl-2-alkenyl, 1-cyclohexyl-3-alkenyl, cyclohexadienyl and the like. Depending on the structure, cycloalkyl groups can be monovalent or divalent groups, i.e., cycloalkylene. C4Cycloalkyl means cyclobutyl, C5Cycloalkyl means cyclopentyl, C7Cycloalkyl refers to cycloheptyl. Cycloalkyl groups may be substituted with substituents described herein.
The term "aryl" may be monocyclic, bicyclic and tricyclic carbocyclic ring systems, wherein at least one ring system is aromatic, wherein each ring system contains 6 to 8 atoms and only one attachment point is attached to the rest of the molecule. The term "aryl" may be used interchangeably with the term "aromatic ring", e.g., aromatic rings may include phenyl, naphthyl, and anthracene. Depending on the structure, the aryl group can be a monovalent group or a divalent group, i.e., an arylene group. The aryl group may be substituted with the substituent described in the present invention.
The terms "heteroaryl", "heteroaryl ring" and "heteroaromatic ring" are used interchangeably herein and all refer to monocyclic, bicyclic, tricyclic or tetracyclic ring systems in which the bicyclic, tricyclic or tetracyclic heteroaromatic ring systems form a ring in fused form. Wherein at least one ring system of the heteroaromatic ring system is aromatic and one or more atoms of the ring are independently optionally substituted with heteroatoms. The heteroaryl system may be attached to the main structure at any heteroatom or carbon atom that results in the formation of a stable compound. The heteroaryl group may be a single ring of 3 to 7 atoms.
In other embodiments, heteroaryl systems (including heteroaryl, heteroaryl rings) include, but are not limited to, the following examples: furan-2-yl, furan-3-yl, N-imidazolyl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, isoxazol-3-yl, oxazol-4-yl, oxazol-5-yl, 4-methylisoxazol-5-yl, N-pyrrolyl, pyrrol-2-yl, pyrrol-3-yl, pyridin-2-yl, pyridin-3-yl, oxazinyl, thiazol-2-yl, tetrazolyl, triazolyl and the like. Heteroaryl groups may be substituted with substituents described herein.
"heterocyclyl" may be a carbon or heteroatom radical. "Heterocyclyl" also includes heterocyclic groups fused to saturated or partially unsaturated carbocyclic or heterocyclic rings. Examples of heterocycles include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, thiaheteroalkyl, azetidinyl, thietanyl, piperidinyl, epoxypropyl, azepinyl, oxepinyl, thiepinyl, N-morpholinyl, 2-morpholinyl, 3-morpholinyl, thiomorpholinyl, N-piperazinyl, 2-piperazinyl, 3-piperazinyl, homopiperazinyl, oxazepinyl, diazepinyl, thiazepinyl, pyrrolin-1-yl, 2-pyrrolinyl, 3-pyrrolinyl, indolinyl, indolizinyl, indolyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl.
In some embodiments, heterocyclyl is 1-12 member heterocyclyl and refers to a saturated or partially unsaturated monocyclic ring containing 1-12 ring atoms, wherein at least one ring atom is selected from nitrogen, sulfur, and oxygen atoms. Examples of heterocyclic groups of 1 to 12 atoms include, but are not limited to, azetidinyl, oxetanyl, pyrrolidinyl, 2-pyrrolinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, 1, 3-dioxolanyl, dithiocyclopentyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, and the like.
The terms "spirocyclic", "spiro", "spirobicyclic group", "spirobicyclic ring" indicate that one ring originates from a particular cyclic carbon on the other ring. For example, as described below, a saturated bridged ring system (rings D and B ') is referred to as a "fused bicyclic ring", whereas rings a' and D share a carbon atom in two saturated ring systems, and are referred to as "spiro rings". Each ring within the spiro ring is either a carbocyclic or a heteroalicyclic. Examples of such include, but are not limited to, spiro [2.4] heptan-5-yl, spiro [4.4] nonanyl, and the like.
The term "spiroheterobicyclic group" means that one ring originates from a specific cyclic carbon on the other ring. For example, as described above, a saturated bridged ring system (rings D and B ') is referred to as a "fused bicyclic ring", whereas rings a' and D share a carbon atom in two saturated ring systems, is referred to as a "spiro ring". And at least one ring system contains one or more heteroatoms, examples of which include, but are not limited to, 4-azaspiro [2.4] heptylalkyl, 4-oxaspiro [2.4] heptylalkyl, 5-azaspiro [2.4] heptylalkyl, 2-azaspiro [4.5] decanyl, 2-azaspiro [3.3] heptanyl, 1, 7-diazaspiro [4.4] nonanyl, 1, 7-diazaspiro [4.4] nonan-6-one-yl, 2, 9-diazaspiro [5.5] undecan-1-one-yl, 1-oxo-3, 8-diazaspiro [4.5] decan-2-one-yl, 1-oxo-3, 7-diazaspiro [4.5] decan-2-one-yl, 2, 6-diazaspiro [3.3] heptanyl, 2-oxo-7-azaspiro [3.5] nonanyl, 2-oxo-6-azaspiro [3.4] octanyl, and the like. Depending on the structure, the spiroheterobicyclic group can be a monovalent group or a divalent group, i.e., a spiroheterobicyclic group. The spiroheterocyclyl group may be substituted with the substituents described herein.
The terms "fused bicyclic", "fused ring", "fused bicyclic group" or "fused ring group" mean a fused ring system, saturated or unsaturated, and refers to a non-aromatic bicyclic ring system, at least one of the rings being non-aromatic. Such systems may contain independent or conjugated unsaturation, but the core structure does not contain aromatic or heteroaromatic rings. Each ring in the fused bicyclic ring can be either a carbocyclic or a heteroalicyclic, and examples include, but are not limited to, hexahydro-furan [3,2-b ] furanyl, 2,3,3a,4,7,7 a-hexahydro-1H-indenyl, 7-azabicyclo [2.2.1] heptanyl, fused bicyclo [3.3.0] octanyl, fused bicyclo [3.1.0] hexanyl, 1,2,3,4,4a,5,8,8 a-octahydronaphthyl, all of which are included in the fused bicyclic ring system.
The term "fused heterobicyclic group" refers to a saturated or unsaturated fused ring system, involving a non-aromatic bicyclic ring system, at least one of the rings being non-aromatic. Such systems may contain independent or conjugated unsaturation states, but the core structure does not contain aromatic or heteroaromatic rings (although aromatics may be substituents thereon), and at least one ring system contains one or more heteroatoms.
Example 1
Poly (ethylene oxide) monomethyl ether (PEG2000, average molecular weight M) (0.075mmol, 150mg)n2000g/mol) and (0.05mmol, 60mg) hexa [ tris (dimethylamine) phosphazene]The triphosphazene is added into a reaction tube, the reaction tube is placed in a low-temperature cold bath at minus 40 ℃, 1.2mL of dichloromethane is added, the mixture is stirred for 10min to ensure that the system is uniformly mixed, the reaction tube is placed in a low-temperature cold bath at minus 50 ℃, and 1.15mL of gamma-butyrolactone is added into the reaction tube by an injector. The reaction was carried out for 4h under nitrogen, acetic acid (0.15mmol) was added, the reaction mixture was poured into excess methanol, and the precipitate was separated by centrifugation to give polyethylene oxide-b-poly (. gamma. -butyrolactone), the structure of which is shown below:
nuclear magnetic hydrogen spectrum1H NMR(500MHz，CDCl3) δ (ppm): 4.11(425H, t), 3.65(180H, s), 3.38(3H, s), 2.39(426H, t), 1.96(438H, m). Nuclear magnetic carbon spectrum13C NMR(126MHz，CDCl3) δ (ppm): 172.6, 70.48, 63.44, 30.56, 23.89. The number-average molecular weight was 16.5kg/mol and the molecular weight distribution was 1.33 as determined by GPC. The nuclear magnetic hydrogen spectrum, the carbon spectrum, the GPC curve and the infrared spectrum of the obtained block copolymer are respectively shown in FIG. 1, FIG. 4, FIG. 5 and FIG. 10, respectively.
Example 2
Poly (ethylene oxide) monomethyl ether (PEG2000, average molecular weight M) (0.075mmol, 150mg)n2000g/mol) and (0.05mmol, 60mg) hexa [ tris (dimethylamine) phosphazene]The triphosphazene is added into a reaction tube, the reaction tube is placed in a low-temperature cold bath at minus 40 ℃, 0.6mL of dichloromethane is added, the mixture is stirred for 10min to ensure that the system is uniformly mixed, the reaction tube is placed in a low-temperature cold bath at minus 50 ℃, and 0.57mL of gamma-butyrolactone is added into the reaction tube by an injector. The reaction is carried out for 4h under the protection of nitrogen, and thenAcetic anhydride (0.3mmol) was added, the reaction mixture was poured into excess methanol, and the precipitate was centrifuged to give polyethylene oxide-b-poly (. gamma. -butyrolactone), the structure of which is shown below:
nuclear magnetic hydrogen spectrum1H NMR(500MHz，CDCl3) δ (ppm): 4.11(160H, t), 3.65(180H, s), 3.38(3H, s), 2.39(163H, t), 1.96(180H, m). The number average molecular weight by GPC was 11.7kg/mol, with a molecular weight distribution of 1.93. The nuclear magnetic hydrogen spectrum of the obtained block copolymer is shown in FIG. 2, and the GPC curve is shown in FIG. 6.
Example 3
Poly (ethylene oxide) monomethyl ether (PEG5000, average molecular weight M) (0.075mmol, 375mg)n5000g/mol) and (0.05mmol, 60mg) hexa [ tris (dimethylamine) phosphazene]The triphosphazene is added into a reaction tube, the reaction tube is placed in a low-temperature cold bath at minus 50 ℃, 0.6mL of dichloromethane is added, the system is uniformly mixed by stirring for 10min, and 0.57mL of gamma-butyrolactone is added into the reaction tube by an injector. The reaction was carried out for 4h under nitrogen protection, acryloyl chloride (0.15mmol) was added, the reaction mixture was poured into excess methanol, and the precipitate was centrifuged to give polyethylene oxide-b-poly (. gamma. -butyrolactone), the structure of which is shown below:
nuclear magnetic hydrogen spectrum1H NMR(500MHz，CDCl3) δ (ppm): 4.11(312H, t), 3.65(450H, s), 3.38(3H, s), 2.39(309H, t), 1.96(314H, m). The number-average molecular weight was 10.9kg/mol and the molecular weight distribution was 2.50 by GPC. The nuclear magnetic hydrogen spectrum of the obtained block copolymer is shown in FIG. 3, the GPC curve is shown in FIG. 7, and the infrared spectrum is shown in FIG. 11.
Example 4
Poly (ethylene oxide) monomethyl ether (PEG2000, average molecular weight M) (0.075mmol, 152mg)n2000g/mol) and (0.15mmol, 3.6mg) NaH were added to a reaction flask, and 5 was addedAnd (3) mL of tetrahydrofuran, carrying out reflux reaction for 24 hours under the protection of nitrogen, filtering the reaction mixture, and draining the filtrate to obtain the polyethylene oxide monomethyl ether sodium. Adding 0.2mL of tetrahydrofuran into the obtained polyethylene oxide monomethyl ether sodium, stirring for 10min, placing in a low-temperature cooling bath at the temperature of minus 50 ℃, adding 0.4mL of dichloromethane, stirring for 10min to uniformly mix the system, and adding 0.57mL of gamma-butyrolactone into a reaction tube by using an injector. The reaction was carried out for 4h under nitrogen protection, epichlorohydrin (7.5mmol) was added, the reaction mixture was poured into excess methanol, and polyethylene oxide-b-poly (γ -butyrolactone) was obtained by centrifugal separation and precipitation, the structure of which is shown below:
the number average molecular weight was 12.4kg/mol and the molecular weight distribution was 1.48 by GPC. The GPC curve of the obtained block copolymer is shown in FIG. 8.
Example 5
Poly (ethylene oxide) monomethyl ether (PEG2000, average molecular weight M) (0.075mmol, 150mg)n2000g/mol) and (0.15mmol, 10.5mg) potassium methoxide were added to the reaction tube, 0.2mL of tetrahydrofuran was added, the mixture was placed in a low-temperature cooling bath at-50 ℃, 0.4mL of dichloromethane was added, the mixture was stirred for 10min to mix the system uniformly, and 0.57mL of γ -butyrolactone was added to the reaction tube by means of a syringe. The reaction was carried out for 4h under nitrogen, 4-methoxyphenyl isocyanate (0.6mmol) was added, the reaction mixture was poured into excess methanol, and the precipitate was centrifuged to give polyethylene oxide-b-poly (. gamma. -butyrolactone), which has the following structure:
the number average molecular weight was 4.5kg/mol as determined by GPC, and the molecular weight distribution was 1.66. The GPC curve of the obtained block copolymer is shown in FIG. 9.
Example 6
A mixture of (0.15mmol, 150mg) polyethylene oxide (PEG1000, average molecular weight M)n1000g/mol) and (0.3mmol, 6.9mg) sodium were added to the reaction tubeAdding 0.2mL of tetrahydrofuran, stirring for 60min at 25 ℃ under the protection of nitrogen, placing in a low-temperature cooling bath at-50 ℃, adding 0.4mL of dichloromethane, stirring for 10min to uniformly mix the system, and adding 1.15mL of gamma-butyrolactone into a reaction tube. The reaction was carried out for 2h under nitrogen protection, succinic anhydride (0.45mmol) was added, the reaction mixture was poured into excess methanol, and the precipitate was centrifuged to give poly (γ -butyrolactone) -b-polyethylene oxide-b-poly (γ -butyrolactone), the structure of which is shown below:
the number-average molecular weight was 6.1kg/mol and the molecular weight distribution was 1.45 by GPC.
Example 7
Poly (propylene oxide) monomethyl ether (PPG2500, average molecular weight M) (0.1mmol, 250mg)n2500g/mol) and (0.1mmol, 17.7mg) sodium biphenyl were added to a reaction tube, 0.3mL tetrahydrofuran was added, stirred at 25 ℃ for 30min under nitrogen protection, placed in a-50 ℃ low temperature cold bath, 0.5mL dichloromethane was added, stirred for 10min to mix the system uniformly, and 0.77mL γ -butyrolactone was added to the reaction tube. The reaction is carried out for 4h under the protection of nitrogen, 3-chloropropene (0.2mmol) is added, the reaction mixture is poured into excessive methanol, and polypropylene oxide-b-poly (gamma-butyrolactone) is obtained by centrifugal separation and precipitation, and the structure is shown as follows:
the number average molecular weight was 4.4kg/mol and the molecular weight distribution was 1.35 as determined by GPC.
Example 8
Poly (ethylene oxide-b-poly (propylene oxide) -b-poly (ethylene oxide) (PEG-b-PPG-b-PEG, average molecular weight M) (0.1mmol, 200mg)n2000g/mol) and (0.1mmol, 63.4mg) phosphazene ligand P4-tert-butyl (tert-Bu-P)4) Adding into a reaction tube, placing in a low temperature cooling bath at-50 deg.C, adding 1mL of dichloromethane, stirring for 10min to mix the system uniformly, adding 0.77mL of gamma-butyrolactone with a syringeInto a reaction tube. The reaction was carried out for 4h under nitrogen, 4-methoxyphenyl thioisocyanate (0.3mmol) was added, the reaction mixture was poured into excess methanol, and the precipitate was separated by centrifugation to give poly (γ -butyrolactone) -b-polyethylene oxide-b-polypropylene oxide-b-polyethylene oxide-b-poly (γ -butyrolactone), which had the following structure:
the number average molecular weight was 6.5kg/mol as determined by GPC, with a molecular weight distribution of 1.56.
Example 9
Poly (ethylene oxide-ran-propylene oxide) (PEG-ran-PPG, average molecular weight M) (0.075mmol, 187.5mg)n2500g/mol) and (0.15mmol, 3.6mg) NaH were added to a reaction flask, 5mL of tetrahydrofuran was added, the reaction was refluxed for 24h under nitrogen protection, the reaction mixture was filtered, and the filtrate was dried by suction to give sodium poly (ethylene oxide-ran-propylene oxide). Adding 0.2mL of tetrahydrofuran into the obtained poly (ethylene oxide-ran-propylene oxide) sodium, stirring for 10min, placing in a low-temperature cooling bath at minus 50 ℃, adding 0.4mL of dichloromethane, stirring for 10min to uniformly mix the system, and adding 0.57mL of gamma-butyrolactone into a reaction tube by using an injector. The reaction was carried out for 4h under nitrogen, maleimidobutyryl chloride (0.45mmol) was added, the reaction mixture was poured into excess methanol, and the precipitate was centrifuged to give poly (γ -butyrolactone) -b-poly (ethylene oxide-ran-propylene oxide) -b-poly (γ -butyrolactone), which has the following structure:
the number average molecular weight was 10.4kg/mol and the molecular weight distribution was 1.41 as determined by GPC.
Example 10
Compounds were prepared according to the procedure of example 1, except that acetic acid was replaced with the reactive functional group-containing compound shown in Table 1, to give the corresponding polyether-b-poly (. gamma. -butyrolactone) block copolymer.
TABLE 1
Example 11
Compounds were prepared according to the procedure of example 6, except that succinic anhydride was replaced with the reactive functional group-containing compound shown in Table 2, to give the corresponding polyether-b-poly (. gamma. -butyrolactone) block copolymer.
TABLE 2
Example 12
A compound was prepared according to the procedure of example 7, except that 3-chloropropene was replaced with a reactive functional group-containing compound shown in Table 3, to thereby obtain the corresponding polyether-b-poly (gamma-butyrolactone) block copolymer.
TABLE 3
Example 13
A compound was prepared according to the procedure for example 8, except that 4-methoxyphenyl thioisocyanate was replaced with a reactive functional group-containing compound shown in Table 4, to thereby obtain the corresponding polyether-b-poly (. gamma. -butyrolactone) block copolymer.
TABLE 4
Example 14
A compound was prepared according to the procedure of example 9, except that maleimidobutyryl chloride was replaced with a compound having a reactive functional group shown in Table 5, to thereby obtain the corresponding polyether-b-poly (gamma-butyrolactone) block copolymer.
TABLE 5
Example 15
Compounds were prepared according to the procedure of example 6, except that polyethylene oxide was replaced with polypropylene oxide and succinic anhydride was replaced with the reactive functional group-containing compound shown in Table 6, to give the corresponding polyether-b-poly (. gamma. -butyrolactone) block copolymer.
TABLE 6
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.
Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.
Claims (10)
1. A copolymer is characterized in that the copolymer is shown as a formula (I),
wherein the content of the first and second substances,
r is selected from alkyl, alkenyl, alkynyl, alkoxy, alkylamino, cycloalkyl, heterocyclic group, aryl, heteroaryl, fused bicyclic group, spiro bicyclic group, fused heterobicyclic group, spiro heterobicyclic group or a group shown in formula (II),
R1selected from hydrogen orA group of one of the following:
R2a group selected from one of the following:
R3and R4Each independently selected from one of the following:
x, y and n are each independently selected from natural numbers of not less than 5.
2. The copolymer of claim 1, having a structure of one of:
wherein each R is5Each independently selected from hydrogen, methyl or ethyl.
3. The copolymer of claim 1, having a structure of one of:
4. a process for preparing the copolymer according to any one of claims 1 to 3, comprising:
(1) dissolving a catalyst or an alkali metal compound or an alkali metal alkoxy compound and hydroxyl-terminated polyether in an organic solvent to obtain a mixed solution;
(2) mixing gamma-butyrolactone with the mixed solution, reacting, adding a compound containing an active functional group to terminate the reaction, adding the reaction mixture into methanol, and collecting the precipitate, so as to obtain the copolymer, wherein the reaction is carried out at-70 to-20 ℃;
the alkali metal compound is selected from sodium hydride, potassium hydride, sodium naphthalene, potassium naphthalene, sodium biphenyl, sodium diphenylmethyl or potassium diphenylmethyl.
5. The method of claim 4, wherein the catalyst is selected from the group consisting of organophosphazene base catalysts;
the alkali metal is selected from sodium or potassium;
the alkali metal alkoxy compound is selected from potassium methoxide, sodium ethoxide or potassium ethoxide;
the hydroxyl-terminated polyether is selected from polyethylene oxide monomethyl ether, polypropylene oxide monomethyl ether, poly (1, 2-butylene oxide) monomethyl ether, polyethylene oxide, polypropylene oxide, poly (1, 2-butylene oxide), polyethylene oxide-b-polypropylene oxide-b-polyethylene oxide or poly (ethylene oxide-ran-propylene oxide);
the compound containing active functional groups is selected from acid, acyl chloride, acid anhydride, thioisocyanate, isocyanate or halogenated hydrocarbon.
6. The method of claim 4, wherein the catalyst is selected from the group consisting of hexa [ tris (dimethylamine) phosphazene ] triphosphazene, phosphazene ligand P4-t-butyl, and phosphazene ligand P2-t-butyl;
the compound containing the active functional group is selected from acetic acid, benzoic acid, acryloyl chloride, methacryloyl chloride, acetic anhydride, succinic anhydride, maleimidobutyryl chloride, epichlorohydrin, 3-chloropropene, 3-chloropropyne, 4-methoxyphenyl thioisocyanate and 4-methoxyphenyl isocyanate.
7. The method of claim 4, comprising:
(1-1) dissolving hydroxyl-terminated polyether and a catalyst in an organic solvent, and stirring in a low-temperature cold bath;
(1-2) adding gamma-butyrolactone to the mixed solution obtained in the step (1-1), reacting, adding a compound having a reactive functional group to terminate the reaction, adding the reaction mixture to methanol, collecting the precipitate, to obtain the copolymer,
wherein the content of the first and second substances,
the molar ratio of the catalyst to the hydroxyl-terminated polyether is 1: 3-2: 1;
the organic solvent is at least one selected from tetrahydrofuran, dichloromethane, trichloromethane, 1-dichloroethane, 1, 2-dichloroethane, 1,2, 2-tetrachloroethane, acetonitrile and dioxane;
the low-temperature cold bath stirring is carried out for 10-30 min at the temperature of-70 to-10 ℃.
8. The method of claim 4, comprising:
(2-1) dissolving hydroxyl-terminated polyether and alkali metal or alkali metal compound in an organic solvent, reacting under the protection of nitrogen, and filtering to obtain polyether alkali metal salt solution;
(2-2) dissolving the polyether alkali metal salt solution and gamma-butyrolactone in an organic solvent to effect a reaction, adding a compound having a reactive functional group to terminate the reaction, adding the reaction mixture to methanol, collecting the precipitate, to obtain the copolymer,
wherein the content of the first and second substances,
the molar ratio of the hydroxyl-terminated polyether to the alkali metal or alkali metal compound is 1: 1-1: 10;
in the step (2-1), the reaction temperature is 25-70 ℃, the reaction time is 0.5-72 hours, and the organic solvent is selected from tetrahydrofuran or dioxane;
in the step (2-2), the organic solvent is at least one selected from the group consisting of tetrahydrofuran, dichloromethane, chloroform, 1-dichloroethane, 1, 2-dichloroethane, 1,2, 2-tetrachloroethane, acetonitrile and dioxane;
the molar ratio of the polyether alkali metal salt to the gamma-butyrolactone is 1: 10-1: 200.
9. the method of claim 4, comprising:
(3-1) dissolving hydroxyl-terminated polyether and alkali metal alkoxy compound in organic solvent, and stirring in low-temperature cold bath;
(3-2) adding gamma-butyrolactone to the mixed solution obtained in the step (3-1), reacting, adding a compound having an active functional group to terminate the reaction, adding the reaction mixture to methanol, collecting the precipitate, to obtain the copolymer,
wherein the content of the first and second substances,
the molar ratio of the alkali metal alkoxy compound to the hydroxyl-terminated polyether is 1: 1-2: 1;
the organic solvent is at least one selected from tetrahydrofuran, dichloromethane, trichloromethane, 1-dichloroethane, 1, 2-dichloroethane, 1,2, 2-tetrachloroethane, acetonitrile and dioxane;
the low-temperature cold bath stirring is carried out for 10-30 min at the temperature of-70 to-10 ℃.
10. The method according to claim 4, wherein the hydroxyl-terminated polyether has a molecular weight of 200 to 40000g/mol, and the molar ratio of the hydroxyl-terminated polyether to γ -butyrolactone is 1: 10-1: 200 of a carrier; the molar concentration of the gamma-butyrolactone in the system is 2-10 mol/L; the molar ratio of the compound containing the active functional group to the hydroxyl-terminated polyether is 1: 1-10: 1;
the reaction is carried out at-70 to-20 ℃ for 0.5 to 12 hours.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810109765.7A CN110117359B (en) | 2018-02-05 | 2018-02-05 | Polyether-b-poly (gamma-butyrolactone) block copolymer and preparation method thereof |
| PCT/CN2019/072214 WO2019149086A1 (en) | 2018-02-05 | 2019-01-17 | POLYETHER-B-POLY (γ-BUTYROLACTONE) BLOCK COPOLYMER AND PREPARATION METHOD THEREFOR |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810109765.7A CN110117359B (en) | 2018-02-05 | 2018-02-05 | Polyether-b-poly (gamma-butyrolactone) block copolymer and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110117359A CN110117359A (en) | 2019-08-13 |
| CN110117359B true CN110117359B (en) | 2021-12-21 |
Family
ID=67477922
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810109765.7A Active CN110117359B (en) | 2018-02-05 | 2018-02-05 | Polyether-b-poly (gamma-butyrolactone) block copolymer and preparation method thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN110117359B (en) |
| WO (1) | WO2019149086A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113423762A (en) * | 2019-02-20 | 2021-09-21 | 株式会社钟化 | Method for producing organic polymer having carbon-carbon triple bond |
| CN110478332A (en) * | 2019-09-12 | 2019-11-22 | 青岛科技大学 | A kind of preparation method of novel polyethylene glycol gamma butyrolactone di-block copolymer nano drug-carrying microsphere |
| CN115612049A (en) * | 2021-07-16 | 2023-01-17 | 上海凯赛生物技术股份有限公司 | Spider silk structure-imitating compound and preparation method and application thereof |
| CN114276524B (en) * | 2021-12-27 | 2023-04-21 | 青岛科技大学 | Preparation method of high molecular weight degradable recyclable polyester containing double bond side group |
| CN116254078B (en) * | 2022-09-09 | 2023-08-29 | 浙江铂淳新材料股份有限公司 | Easily-stripped thermal-sticky pressure-sensitive adhesive and preparation process thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101280094A (en) * | 2008-05-27 | 2008-10-08 | 厦门大学 | Bioactive aquagel-conductive polymer nanometer composite material and synthetic material thereof |
| US20150158983A1 (en) * | 2012-08-21 | 2015-06-11 | Industry-Academic Cooperation Foundation Gyeongsang National University | Poly(4-hydroxybutyrate)-b-monomethoxy(polyethylene glycol) copolymer nanoparticles, production method for same and pharmaceutical composition for brain disorder treatment containing same as active ingredient |
| CN107207696A (en) * | 2015-01-02 | 2017-09-26 | 耶路撒冷希伯来大学伊森姆研究发展有限公司 | Biodegradable polymer |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1049905C (en) * | 1994-05-03 | 2000-03-01 | 中国科学院成都有机化学研究所 | Method for copolymerization of internal ester (or lactide) and polyether glycol |
| ITTO20130431A1 (en) * | 2013-05-28 | 2014-11-29 | Fond Istituto Italiano Di Tecnologia | COPOLYMER AND NANOPARTICLES OBTAINED FROM THEM FOR THE DRIVING OF A DRUG |
-
2018
- 2018-02-05 CN CN201810109765.7A patent/CN110117359B/en active Active
-
2019
- 2019-01-17 WO PCT/CN2019/072214 patent/WO2019149086A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101280094A (en) * | 2008-05-27 | 2008-10-08 | 厦门大学 | Bioactive aquagel-conductive polymer nanometer composite material and synthetic material thereof |
| US20150158983A1 (en) * | 2012-08-21 | 2015-06-11 | Industry-Academic Cooperation Foundation Gyeongsang National University | Poly(4-hydroxybutyrate)-b-monomethoxy(polyethylene glycol) copolymer nanoparticles, production method for same and pharmaceutical composition for brain disorder treatment containing same as active ingredient |
| CN107207696A (en) * | 2015-01-02 | 2017-09-26 | 耶路撒冷希伯来大学伊森姆研究发展有限公司 | Biodegradable polymer |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019149086A1 (en) | 2019-08-08 |
| CN110117359A (en) | 2019-08-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110117359B (en) | Polyether-b-poly (gamma-butyrolactone) block copolymer and preparation method thereof | |
| CN110804163B (en) | Preparation method of bio-based copolyester containing modifiable functional group | |
| CN108250415B (en) | Poly (gamma-butyrolactone) -b-polylactic acid block copolymer and preparation method thereof | |
| CN109627429B (en) | Preparation method of high molecular weight poly (gamma-butyrolactone) | |
| KR101160980B1 (en) | Polysiloxane-polylactide block copolymer and preparation method thereof | |
| US9932440B2 (en) | Catalysts and methods for ring opening metathesis polymerization | |
| JP5458216B2 (en) | Process for producing biodegradable polylactic acid for medical use by polycondensation from lactic acid catalyzed by creatinine | |
| US20160128940A1 (en) | Docetaxel nano-polymer micelle lyophilized preparation and preparation method thereof | |
| WO2012167171A2 (en) | Z-selective ring-closing metathesis reactions | |
| US20200231760A1 (en) | Block copolymers of lactones and poly(propylene fumarate) | |
| CN105694008B (en) | A kind of preparation method of the adjustable macromolecule polyester composite of biodegradation rate | |
| CN109836561B (en) | Synthesis method of 6-hydroxycaproic acid oligomer and oligomer obtained by same | |
| CN105949449A (en) | Composite catalyst for preparing polyether-polylactide-aliphatic polycarbonate ternary block copolymer and application of composite catalyst | |
| Lee et al. | Ring-opening polymerization of a macrocyclic lactone monomer isolated from oligomeric byproducts of poly (butylene succinate)(PBS): An efficient route to high-molecular-weight PBS and block copolymers of PBS | |
| JP6014018B2 (en) | New polyester ethers derived from asymmetric monomers based on bisaanhydrohexitol | |
| CN105754107A (en) | Hydrophilic poly(omega-caprolactone) and preparation method thereof | |
| CN117004007A (en) | Crystalline aliphatic polycarbonate with high molecular weight and high mechanical property and preparation method thereof | |
| CN111004373A (en) | Preparation method of medical multi-arm polycaprolactone | |
| CN102875789A (en) | Polyether block copolymer and preparation method thereof | |
| CN101440157B (en) | Copolymer of furan glycidyl ether or ester and carbon dioxide, and preparation thereof | |
| CN107033337B (en) | A kind of functional poly ester polyurethane alternate copolymer and its preparation and application | |
| CN106554342A (en) | 3,6 dichloromethyl Acetic acid, hydroxy-, bimol. cyclic esters and its production and use | |
| CN118184973A (en) | Multifunctional CO2Base copolyester and preparation method thereof | |
| CN117586489A (en) | Method for preparing polyester by catalyzing lactide polymerization reaction by Salen catalyst | |
| CN117820650A (en) | Copolymer material, preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20191115 Address after: Room 608, Jufeng Chuangye building, No. 52, Miaoling Road, Laoshan District, Qingdao, Shandong Province Applicant after: Qingdao Boyuan Polymer Materials Research Institute Co., Ltd Address before: 266061 Shandong Province, Qingdao city Laoshan District Songling Road No. 99 Applicant before: Qingdao University of Science & Technology |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |