A method for synthesizing a cyclic polymer
By synthesizing bromine-terminated polystyrene via the ATRP method and performing a click reaction in Theta solvent, the problems of low yield and low molecular weight in the synthesis of cyclic polymers were solved, and high-purity, high-molecular-weight cyclic polymers were achieved.
Patent Information
- Application Number
- CN202211468183.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-11-22
- Publication Date
- 2025-01-14
- Estimated Expiration
- 2042-11-22
AI Technical Summary
Existing methods for synthesizing cyclic polymers suffer from low yields and low molecular weights. In particular, it is difficult to form high molecular weight cyclic polymers in the ring-closing reaction, which hinders their further research and application.
Atom transfer radical polymerization (ATRP) was used to synthesize polystyrene chains with bromine at the end. These chains were then converted to polystyrene with azide at the end via an azidation reaction. Finally, a click reaction was carried out in a Theta solvent to synthesize cyclic polystyrene. The Theta solvent was used to improve the efficiency of the ring-closing reaction and reduce the distance between functional groups.
It increases the yield of cyclic polymers per batch by 2 to 4 times, with a purity of 96% to 99% and a molecular weight of up to 8×10⁴ g/mol. The reaction rate is faster, the molecular weight of the product is higher, and the purity of the product is higher.
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Figure CN115894752B_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of cyclic polymers, and in particular relates to a method for synthesizing a cyclic polymer. Background Art
[0002] Since the 1950s, various cyclic structures of DNA, peptides, oligosaccharides, polysaccharides, etc. have been discovered and reported one after another. Circular polymers have aroused great research interest among researchers. Compared with linear polymers, cyclic polymers have no end groups, have stronger molecular chain rigidity and smaller conformational entropy, and thus have many unique physical properties, such as higher glass transition temperature, larger refractive index, smaller fluid dynamic volume, lower intrinsic viscosity and moving friction coefficient, etc. Therefore, cyclic polymers have shown unique advantages in the fields of liquid crystals, self-assembly, drug release, etc., and have been widely used.
[0003] So far, there are two main methods for synthesizing cyclic polymers: ring expansion and ring closure. The ring closure method has low requirements for monomers and a wide range of monomer selection, and is currently the main method for synthesizing cyclic polymers. However, during the ring closure reaction, the cyclization reaction needs to be carried out in an extremely dilute solution to avoid condensation reactions between molecules, which results in very low yields of cyclic polymers. In addition, the higher the molecular weight and the greater the end-to-end distance, the more difficult it is to form a ring. Therefore, lower yields and lower molecular weights have become bottlenecks in the synthesis of cyclic polymers, affecting in-depth research and application of cyclic polymers. How to efficiently prepare cyclic polymers is an important topic that urgently needs to be studied in related fields. Summary of the invention
[0004] In order to solve one or more of the above technical problems existing in the prior art, the present invention provides a method for synthesizing a cyclic polymer in a first aspect, the method comprising the following steps:
[0005] (1) Synthesis of linear polymer chains: Synthesize polystyrene chains with bromine at the end by atom transfer radical polymerization (ATRP) using initiators and styrene monomers;
[0006] (2) Terminal group conversion: using a polystyrene chain with bromine at the end, the terminal bromine group is converted to an azide group through an azidation reaction to obtain a polystyrene with azide at the end;
[0007] (3) Synthesis of cyclic polymers: Polystyrene with terminal azide is dissolved in theta solvent, and the azide and alkyne groups undergo a click reaction to synthesize cyclic polystyrene.
[0008] Preferably, the (1) linear polymer chain synthesis comprises: mixing an initiator, a styrene monomer, a ligand and a solvent, followed by deoxygenation (preferably by three freeze-pump-thaw cycles), then adding a catalyst CuBr to initiate polymerization, after a certain period of time, diluting the reaction mixture with THF and quickly passing it through a neutral alumina column to remove copper salts and quench the reaction, then removing the solvent and monomers by rotary evaporation, and precipitating the polymer solution twice in methanol or a mixture of methanol and water, and finally vacuum drying for several hours (1 to 10 hours, preferably 3 to 7 hours) to obtain polystyrene with terminal bromine.
[0009] Preferably, the (2) terminal group conversion comprises: stirring the bromine-containing polystyrene, NaN3 and N,N'-dimethylformamide (DMF) at room temperature for a certain period of time, adding dichloromethane, and then precipitating in methanol or a mixture of methanol and water, dissolving the precipitate with an appropriate amount of THF, and precipitating and purifying it again, and then vacuum drying for several hours (1 to 10 hours, preferably 3 to 7 hours) to obtain the polystyrene with terminal azide.
[0010] Preferably, the (3) cyclic polymer synthesis comprises: adding CuBr, ligand pentamethyldiethylenetriamine (PMDETA) and Theta solvent into a reaction bottle, passing nitrogen to deoxygenate, then placing in an oil bath (preferably an oil bath at 100° C.), dissolving polystyrene with azide in the Theta solvent, and slowly dropping the Theta solution of polystyrene with azide into the reaction system after deoxygenation (preferably placing the Theta solution of polystyrene with azide in a syringe, and then using a peristaltic pump to slowly drop the polystyrene solution in the syringe into the reaction system). After the dropwise addition is completed, the reaction is carried out for several hours, and then the Theta solvent is evaporated, and the remaining crude product solution is passed through a neutral alumina column to remove copper salt, and after concentration, it is precipitated in methanol or a mixture of methanol and water, and vacuum dried to obtain the product, i.e., cyclic polystyrene.
[0011] In a second aspect, the present invention provides a cyclic polymer synthesized by the above method, wherein the production amount of each batch of the cyclic polymer can be increased by 2 to 4 times, the purity is 96% to 99%, and the molecular weight can reach up to 8×10 4 g / mol.
[0012] Compared with the prior art, the present invention has at least the following beneficial effects:
[0013] The synthesis method described in the present invention uses the Theta solvent of the polymer as the reaction solvent for the ring-closing reaction. In the end-end ring-closing reaction, a ring-forming reaction efficiency formula is followed:
[0014]
[0015] Where P r is the ring formation efficiency, υ e is the ring-closing reaction efficiency, R n is the distance between the reaction functional groups. From this formula, we can see that there are two ways to improve the efficiency of the ring-forming reaction: to improve the efficiency of the ring-closing reaction e ; Reduce the distance R between functional groups n . In order to improve the efficiency of the ring-closing reaction, this method uses the efficient Click reaction. In order to reduce the distance between functional groups, this method uses the polymer Theta solvent as the reaction solvent for the ring-closing reaction. The polymer chain exists in the state of undisturbed coils in the Theta solvent and is in an expanded state in the good solvent. In the good solvent and the Theta solvent, the root mean square radius of gyration R of the linear polystyrene chain is g The scaling relationships with molecular weight are:
[0016] R g,θ =0.02675×M 0.5040
[0017] R g,良 =0.01234×M 0.5936
[0018] Among them, R g,θ is the root mean square radius of gyration of a linear polystyrene chain in a Theta solvent, R g,良 It represents the root mean square radius of gyration of linear polystyrene chain in good solvent. As can be seen from the above formula, Theta solvent has a larger radius than good solvent. g Therefore, compared with the good solvent used in the previous synthesis method, the use of Theta solvent can increase the concentration of the ring-closing reaction, thereby increasing the amount of each batch produced. In addition, the ends of the polymer chain in the Theta solvent are closer, which not only increases the reaction speed, but also facilitates the synthesis of higher molecular weight rings. In short, compared with the prior art, the present invention has a faster reaction speed, can generate a higher molecular weight, has a higher purity of the product, and can increase the amount of each batch produced. BRIEF DESCRIPTION OF THE DRAWINGS
[0019] Figure 1 It is a schematic diagram of the synthesis process of the cyclic polymer of the present invention.
[0020] Figure 2 It is a GPC (gel permeation chromatography) chart of the linear chain and the ring chain in Example 1, wherein the abscissa represents the elution time and the ordinate represents the response signal of the differential refractometer.
[0021] Figure 3 This is the GPC chart of the linear chain and the ring chain in Example 2. DETAILED DESCRIPTION
[0022] The present invention is further described in detail below through examples and drawings.
[0023] The present invention provides a method for synthesizing a cyclic polymer. Figure 1 As shown, the method comprises the following steps:
[0024] (1) Synthesis of linear polymer chains: The initiator, styrene monomer, ligand and solvent are mixed, and then deoxygenated by three freeze-pump-thaw cycles. Then, the catalyst CuBr is added to initiate polymerization. After a certain period of time, the reaction mixture is diluted with THF and quickly passed through a neutral alumina column to remove copper salts and quench the reaction. The solvent and monomer are then removed by rotary evaporation, and the polymer solution is precipitated twice in methanol or a mixture of methanol and water. Finally, it is vacuum dried for several hours to obtain polystyrene with terminal bromine.
[0025] (2) Terminal group conversion: polystyrene with bromine, NaN3 and N,N'-dimethylformamide (DMF) are stirred at room temperature for a certain period of time, and then dichloromethane is added, and then precipitated in methanol or a mixture of methanol and water. The precipitate is dissolved with an appropriate amount of THF, and the precipitation is purified again, and then the polystyrene with terminal azide is obtained in a vacuum oven for several hours;
[0026] (3) Synthesis of cyclic polymers: CuBr, ligand pentamethyldiethylenetriamine (PMDETA) and Theta solvent are added to a reaction bottle, nitrogen is passed to deoxygenate, and then placed in an oil bath at 100°C. Polystyrene with azide is dissolved in the Theta solvent. After deoxygenation, the Theta solution of polystyrene with azide is slowly added to the reaction system (preferably, the Theta solution of polystyrene with azide is placed in a syringe, and then the polystyrene solution in the syringe is slowly added to the reaction system using a peristaltic pump). After the addition is completed, the reaction is carried out for several hours, and then the Theta solvent is evaporated, and the remaining crude product solution is passed through a neutral alumina column to remove copper salts. After concentration, it is precipitated in methanol or a mixture of methanol and water, and the product is obtained after vacuum drying.
[0027] In some preferred embodiments, in step (1), the initiator is Figure 1 The substance represented by formula (I) is propargyl bromoisobutyrate. One end of the initiator is a tertiary bromine group and the other end is an alkynyl group. The tertiary bromine end is used to initiate controlled free radical polymerization of styrene, which is then converted into an azide group through an azidation reaction, and then undergoes an efficient click reaction with the alkynyl end of the initiator. The initiator can also be other substances with an alkynyl group at one end and a bromine at the other end.
[0028] In some preferred embodiments, in step (1), the ligand is selected from one of tris(2-dimethylaminoethyl)amine (Me6TREN), 2,2'-bipyridine (bpy) and PMDETA. When Me6TREN is used, stannous octoate (Sn(EH)2) needs to be added.
[0029] In some preferred embodiments, in step (1), the solvent is selected from one of toluene and anisole.
[0030] In some preferred embodiments, in step (1), the molar ratio of the initiator to the styrene monomer is 1:100-1:500 (e.g., 1:100, 1:200, 1:300, 1:400 or 1:500); the molar ratio of the initiator to the ligand is 1:1-1:4 (e.g., 1:1, 1:2, 1:3 or 1:4); the molar ratio of the initiator to the CuBr is 1:0.1-1:2 ( For example, 1:0.1, 1:0.5, 1:1 or 1:2); the volume ratio of the styrene monomer to the solvent is 1:0.5-1:2 (for example, 1:0.5, 1:1, 1:1.5 or 1:2); the volume ratio of methanol to water in the mixture of methanol and water is 1:0.1-1:0.3 (for example, 1:0.1, 1:0.2 or 1:0.3); the molar ratio of the Me6TREN to the Sn(EH)2 is 1:1.
[0031] In some preferred embodiments, in step (1), the reaction temperature is 80-110° C. (e.g., 80° C., 90° C., 100° C. or 110° C.);
[0032] In some preferred embodiments, in step (1), the reaction time is 1 to 48 h (e.g., 1, 6, 12, 24 or 48 h);
[0033] In some preferred embodiments, in step (2), the molar ratio of the bromine-containing polystyrene to NaN3 is 1:3-1:10 (for example, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10); the mass ratio of the bromine-containing polystyrene to DMF is 1:4-1:6 (for example, 1:4, 1:5 or 1:6); the volume ratio of DMF to dichloromethane is 1:0.1-1:0.3 (for example, 1:0.1, 1:0.2 or 1:0.3); the volume ratio of methanol to water in the mixture of methanol and water is 1:0.1-1:0.3 (for example, 1:0.1, 1:0.2 or 1:0.3);
[0034] In some preferred embodiments, in step (2), the reaction time is 48 to 60 h (e.g., 48, 50, 52, 54, 56, 58 or 60 h);
[0035] In some preferred embodiments, in step (3), the Theta solvent is selected from one of cyclopentane and cyclohexane;
[0036] In some preferred embodiments, in step (3), the mass concentration of polystyrene in the Theta solution is in the range of 3.0 to 4.0 g / L (e.g., 3.0, 3.2, 3.4, 3.6, 3.8 or 4.0 g / L); the mass concentration of PMDETA in DMF is 1.5 mg / L; the mass concentration of CuBr in DMF is 80 mg / L;
[0037] In some preferred embodiments, in step (3), the dropping speed is 0.5 to 1 mL / h (e.g., 0.5, 0.6, 0.7, 0.8, 0.9 or 1.0 mL / h);
[0038] In some preferred embodiments, in step (3), the reaction time is 4-7 h (e.g., 4, 5, 6 or 7 h);
[0039] In some preferred embodiments, the amount of the cyclic polymer produced per batch can be increased by 2 to 4 times (e.g., 2, 3 or 4), the purity is 96% to 99% (e.g., 96%, 97%, 98% or 99%), and the molecular weight can be as high as 8×10 4 g / mol.
[0040] In other preferred embodiments, the cyclic polymer is prepared by the synthesis method described in the first aspect of the present invention.
[0041] The present invention is further described below in conjunction with the examples. These examples are only used to illustrate the preferred embodiments of the present invention, and the protection scope of the present invention should not be interpreted as being limited to these examples.
[0042] Example 1
[0043] This embodiment synthesizes a cyclic polymer, and its synthesis method includes the following steps:
[0044] (1) Synthesis of linear polymer chains: Initiator (33.4 mg, 0.173 mmol), styrene (2 mL, 17.3 mmol), Me6TREN (46.3 μL, 0.173 mmol), Sn(EH)2 (56.1 μL, 0.173 mmol) and anisole (2 mL) were added to a three-necked flask equipped with a stirring magnet, and then deoxygenated by three freeze-pump-thaw cycles. After that, catalyst CuBr (2.5 mg, 0.0173 mmol) was added, and then the mixture was placed in a 90°C oil bath. After reacting for 4 h, the reaction mixture was diluted with about 20 mL of THF and quickly passed through a neutral alumina column to remove copper salts to quench the reaction. The solvent and monomers were then removed by rotary evaporation, and the polymer solution was precipitated twice in 20 mL of a mixture of methanol and water (methanol:water=10:1, temperature of 0°C), and finally vacuum dried for several hours (5 hours in this embodiment) to obtain polystyrene with terminal bromine (M W =3200 g / mol, mass 510 mg);
[0045] (2) Terminal group conversion: brominated polystyrene (0.5 g, 0.156 mmol), NaN3 (51 mg, 0.781 mmol) and DMF (3 mL) were placed in a 10 mL round-bottom flask and stirred at room temperature for 48 mL. Dichloromethane (0.3 mL) was then added, and then precipitated in 33 mL of a mixture of methanol and water (methanol: water = 10:1, temperature 0°C). The precipitate was dissolved with an appropriate amount of THF, and purified by precipitation again, and then vacuum dried for several hours (5 hours in this example) to obtain polystyrene with terminal azide (460 mg);
[0046] (3) Synthesis of cyclic polymer: 120 g of cuprous bromide, 2.61 mL of pentamethyldiethylenetriamine and 1.5 L of cyclohexane were added to a 5 L three-necked flask, and then nitrogen was passed through the reaction flask to deoxygenate. The flask was then placed in an oil bath at 100°C, and polystyrene with azide (450 mg) was dissolved in 50 mL of cyclohexane. After deoxygenation, the polystyrene solution was slowly added dropwise to the reaction system using a peristaltic pump. After the addition was completed, the reaction was allowed to proceed for 5 hours, and then the cyclohexane was evaporated. The remaining crude product solution was passed through a neutral alumina column to remove copper salts, and after concentration, it was precipitated in a mixture of methanol and water (methanol: water = 10:1, temperature 0°C), and the product (404 mg) was obtained after vacuum drying.
[0047] The GPC diagrams before and after the final cyclization reaction in this example are as follows: Figure 2 shown.
[0048] Example 2
[0049] This embodiment synthesizes a cyclic polymer, and its synthesis method includes the following steps:
[0050] (1) Synthesis of linear polymer chains: Initiator (33.4 mg, 0.173 mmol), styrene (32 mL, 277 mmol), Me6TREN (46.3 μL, 0.173 mmol), Sn(EH)2 (56.1 μL, 0.173 mmol) and anisole (32 mL) were added to a three-necked flask equipped with a stirring magnet, and then deoxygenated by three freeze-pump-thaw cycles. After that, catalyst CuBr (2.5 mg, 0.0173 mmol) was added, and the mixture was placed in a 90°C oil bath. After reacting for 4 h, the reaction mixture was diluted with about 100 mL of THF and quickly passed through a neutral alumina column to remove copper salts to quench the reaction. The solvent and monomers were then removed by rotary evaporation, and the polymer solution was precipitated twice in 500 mL of methanol. Finally, the mixture was dried under vacuum for several hours (3 hours in this embodiment) to obtain polystyrene with terminal bromine (M W =35000 g / mol, mass 6.08 g);
[0051] (2) Terminal group conversion: brominated polystyrene (6 g, 0.171 mmol), NaN3 (111 mg, 1.71 mmol) and DMF (36 mL) were placed in a 10 mL round-bottom flask and stirred at room temperature for 48 mL. Dichloromethane (4 mL) was then added and precipitated in 400 mL of methanol. The precipitate was dissolved with an appropriate amount of THF and purified by precipitation again. After that, it was vacuum dried for several hours (3 hours in this example) to obtain polystyrene with terminal azide (5.2 g);
[0052] (3) Synthesis of cyclic polymer: 120 g of cuprous bromide, 2.61 mL of pentamethyldiethylenetriamine and 1.5 L of cyclohexane were added to a 5 L three-necked flask, and then nitrogen was passed through the reaction flask to remove oxygen. The flask was then placed in an oil bath at 100°C, and polystyrene with azide (400 mg) was dissolved in 50 mL of cyclohexane. After deoxygenation, the polystyrene solution was slowly added dropwise to the reaction system using a peristaltic pump. After the addition was completed, the reaction was allowed to proceed for 5 hours, and then the cyclohexane was evaporated. The remaining crude product solution was passed through a neutral alumina column to remove copper salts, concentrated, and precipitated in methanol. The product (382 mg) was obtained after vacuum drying.
[0053] The GPC diagrams before and after the final cyclization reaction in this example are as follows: Figure 3 shown.
[0054] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims
1. A method for synthesizing a cyclic polymer, characterized in that: The method comprises the following steps: (1) Synthesizing polystyrene chains with bromine at the end by atom transfer radical polymerization using an initiator and styrene monomer; (2) using a polystyrene chain with bromine at the end, converting the terminal bromine group to an azide group through an azidation reaction to obtain a polystyrene with azide at the end; (3) Dissolving polystyrene with azide at the end in Theta solvent, the azide and the alkyne group undergo a click reaction to synthesize cyclic polystyrene; Wherein, steps (1) to (3) specifically include: (1) an initiator, a styrene monomer, a ligand and a solvent are mixed, then deoxygenated, and then a catalyst CuBr is added to initiate polymerization. After a certain period of time, the reaction mixture is diluted with THF and quickly passed through a neutral alumina column to remove copper salts and quench the reaction. The solvent and monomer are then removed by rotary evaporation, and the polymer solution is precipitated twice in methanol or a mixture of methanol and water, and finally vacuum dried for several hours to obtain a polystyrene with terminal bromine; (2) stirring the bromine-containing polystyrene, NaN3 and DMF at room temperature for a certain period of time, then adding dichloromethane, and then precipitating in methanol or a mixture of methanol and water, dissolving the precipitate with an appropriate amount of THF, and precipitating and purifying it again, and then vacuum drying for several hours to obtain the polystyrene with terminal azide; (3) CuBr, ligand PMDETA and Theta solvent are added to a reaction bottle, nitrogen is passed through to deoxygenate, and then the reaction bottle is placed in an oil bath. Polystyrene with azide is dissolved in the Theta solvent. After deoxygenation, the Theta solution of polystyrene with azide is slowly added dropwise to the reaction system. After the addition is completed, the reaction is carried out for several hours, and then the Theta solvent is evaporated, and the remaining crude product solution is passed through a neutral alumina column to remove copper salts. After concentration, the solution is precipitated in methanol or a mixture of methanol and water, and vacuum dried to obtain the product, i.e., cyclic polystyrene. In step (1), the molar ratio of the initiator to the styrene monomer is 1:100-1:500; the molar ratio of the initiator to the ligand is 1:1-1:4; the molar ratio of the initiator to the CuBr is 1:0.1-1:2; the volume ratio of the styrene monomer to the solvent is 1:0.5-1:2; the volume ratio of methanol to water in the mixture of methanol and water is 1:0.1-1:0.3; in step (1), the ligand is selected from one of Me6TREN, 2,2'-bipyridine (bpy) and PMDETA, and when Me6TREN is used, Sn(EH)2 needs to be added; the molar ratio of Me6TREN to Sn(EH)2 is 1:1; In step (1), the reaction temperature is 80 to 110° C. and the reaction time is 1 to 48 hours; In step (2), the molar ratio of the brominated polystyrene to NaN3 is 1:3-1:10; the mass ratio of the brominated polystyrene to DMF is 1:4-1:6; the volume ratio of DMF to dichloromethane is 1:0.1-1:0.3; the volume ratio of methanol to water in the mixture of methanol and water is 1:0.1-1:0.3; in step (2), the reaction time is 48-60h; In step (3), the Theta solvent is selected from one of cyclopentane and cyclohexane; In step (3), the mass concentration of polystyrene in the Theta solution is in the range of 3.0 to 4.0 g / L; the mass concentration of PMDETA in DMF is 1.5 mg / L; the mass concentration of CuBr in DMF is 80 mg / L; in step (3), the dripping speed is 0.5 to 1 mL / h, and the reaction time is 4 to 7 h; The production amount of the cyclic polymer per batch can be increased by 2 to 4 times, the purity is 96% to 99%, and the molecular weight can reach up to 8×10 4 g / mol.
2. The method for synthesizing a cyclic polymer according to claim 1, characterized in that: The solvent is selected from one of toluene and anisole.
3. A cyclic polymer, characterized in that The cyclic polymer is obtained by the synthesis method according to claim 1 or 2.
Citation Information
Patent Citations
Cyclic polystyrene and preparation method thereof
CN108467445A