A method for preparing an amphiphilic polymer

Abstract

The application provides a preparation method of an amphiphilic polymer. The application discloses a preparation method of a polymer shown in formula V, which comprises the following steps: performing the reaction shown in the following formula on a polymer shown in formula S6, a compound shown in formula Z6 and a quenching reagent S7 in a solvent in an inert atmosphere to obtain the polymer shown in formula V. When the polymer shown in formula V is prepared by using the method, the reaction condition is mild, the process is reduced, the energy consumption is reduced, the yield is optimized, and the green synthesis of the block copolymer is realized.

Description

Technical Field

[0001] This invention relates to a method for preparing an amphiphilic polymer, belonging to the field of polymers. Background Technology

[0002] Self-assembly at the nanoscale is a key property upon which the formation of biological membranes in nature depends. These membranes construct a functionalized molecular framework by embedding channels, receptors, and molecular pumps within a microenvironment and functional framework. Utilizing hydrophobic-hydrophilic interactions, these membranes self-assemble into other structures such as bilayers and vesicles. Self-assembled membranes are a crucial component if we wish to mimic the principles of natural nanostructures. In recent years, a range of polymer systems have been used for drug delivery, biopharmaceutical coatings, virus-assisted gene delivery, and nanoreactors through their self-assembly. These are amphiphilic diblock or triblock copolymers that self-assemble in suitable solvents into micelles, worm-like micelles, tubular structures, membranes, or vesicles.

[0003] Although block copolymers have many structures, ABA triblock copolymers have received particular attention in recent years due to their inherent ability to form vesicle structures through self-assembly, despite their high hydrophobicity and hydrophilicity. From a biomedical perspective, polyoxazoline provides a pseudopolypeptide structure and is therefore particularly attractive, being selected as the hydrophilic block A. Polymethylsiloxane (PDMS), due to the ionic nature of the Si-CH3 bond, exhibits a very low glass transition temperature and is mostly liquid at room temperature. Furthermore, poly(siloxanes) possess very low surface energy and extremely high hydrophobicity; therefore, they were selected as the hydrophobic block B. Extensive research has been conducted on these ABA triblock copolymer systems, demonstrating their interesting biomedical and self-assembly properties.

[0004] Existing synthetic methods have constructed a series of ABA triblock backbone polymers through a core-first synthetic strategy, but they have drawbacks such as multiple synthetic steps, low yield, high polymer dispersibility, poor reproducibility, and difficulty in modifying molecular structures. Summary of the Invention

[0005] The technical problem this invention aims to solve is that existing methods for synthesizing block copolymers involve numerous steps, use unstable lithium metal reagents, highly toxic pyridine, and other reagents, resulting in low yields, high polymer dispersibility, poor reproducibility, and difficulty in modifying the molecular structure. Therefore, this invention provides a method for preparing amphiphilic polymers.

[0006] This invention provides a polymer as shown in Formula V:

[0007]

[0008] in,

[0009] R is -OR t1 -NR t2 R t3 -COOMe, -(CH2) n1 SH, 5-10 membered heteroaryl groups substituted with 1, 2 or 3 oxo groups, -O(CH2) n2 OH, -OP(O)(OMe), -OP(O)(OMe)(O(CH2) n3 N + (Et)3,

[0010] Wherein, the R t1 R t2 R t3 Independently H, Ts, C1-C6 alkyl, or -(CH2) n4 SH;

[0011] n1, n3, and n4 are independently 0, 1, 2, 3, 4, 5, or 6;

[0012] n2 is 2, 3, 4, 5, 6, 7, 8 or 9;

[0013] The L is

[0014] The In, the R c It can be hydrogen, C1-C6 alkyl, C1-C6 alkoxy, -CN, or -NO2;

[0015] The In this context, n is 1, 2, 3, 4, 5, or 6;

[0016] The In this context, n is 3, 4, 5, 6, 7, 8, or 9;

[0017] The In, the R a (CH2) n n is 3, 4 or 5, and the R b It is hydrogen, C1-C6 alkyl or acetyl;

[0018] The 1 end and the Connected;

[0019] The It is poly(2-methyloxazoline), polyphospholipid, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylamide, polymethyl methacrylate, poly(N,N-dimethylacrylamide), polyamide alkylene imide, polyhydroxyalkyl acrylate, poly(2-methyloxazoline) polyethylene glycol or poly(2-methyloxazoline) polyphospholipid.

[0020] The R 1 It is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C6-C 12 Aryl, -(CH2) n OH、 Or -(CH2) n -CH=CH2, where n is 3, 4 or 5;

[0021] The R 1’ It is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C6-C 12 Aryl, -(CH2) n OH、 Or -(CH2) n -CH=CH2, where n is 3, 4 or 5;

[0022] The Y is a C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, or C6-C6 alkyl group. 12 Aryl, -(CH2) n OH、 Or -(CH2) n -CH=CH2, where n is 3, 4 or 5;

[0023] The value of p is 20-50;

[0024] In the 5-10 membered heteroaryl group, the number of heteroatoms is independently 1, 2 or 3, and the heteroatoms are independently selected from one or more of N, O and S.

[0025] In some implementations, the Preferred Among them, each R 2 Each of the components is independently C1-C3 alkyl, preferably methyl; each m is independently any value from 1 to 22; preferably any value from 1 to 6; more preferably 1, 1.1, 1.3, 3.6, 3.8 or 5.4; even more preferably 3.8 or 5.4; each w is independently any value from 1 to 22; preferably any value from 1 to 6; more preferably 3.

[0026] In some implementations, the Preferred

[0027] In some implementations, the R 1 Preferably, it is a C1-C6 alkyl group. More preferably, it is a methyl group.

[0028] In some implementations, the R 1’Preferably, it is a C1-C6 alkyl group. More preferably, it is a methyl group.

[0029] In some embodiments, the Y is preferably a C1-C6 alkyl group. More preferably, it is methyl.

[0030] In some embodiments, R is preferably hydroxyl, methoxy, TsO-, or... More preferably, hydroxyl or methoxy.

[0031] In some implementations, the L is preferably... Or -CH2-. More preferably,

[0032] In some embodiments, p is preferably any value between 20 and 47. More preferably, it is 30 or 47.

[0033] In some implementations, the R 1 Preferably methyl; the R 1’ Preferably methyl; the Preferred The R 2 Preferably methyl; R is preferably methoxy; Y is preferably methyl; L is preferably... The value of m is preferably 3.8; the value of p is preferably 30.

[0034] In some implementations, the R 1 Preferably methyl; the R 1’ Preferably methyl; the Preferred The R 2 Preferably, R is methyl; R is preferably hydroxyl; Y is preferably methyl; L is preferably... The value of m is preferably 5.4; the value of p is preferably 47.

[0035] In some embodiments, the polymer represented by formula V is

[0036] In some embodiments, the polymer represented by formula V is

[0037] This invention provides a method for preparing the polymer shown in formula V, comprising the following steps: in a solvent and under an inert atmosphere, reacting the polymer shown in formula S6, the compound shown in formula Z6, and the quenching reagent S7 as shown below to obtain the polymer shown in formula V.

[0038]

[0039] Among them, R, L, R 1 R1’ Y and p are defined as described above; X is a halogen, OTf, or OTs; the quenching reagent S7 is an inorganic base (e.g., KOH) or RH, and R is defined as described above; For polymer The corresponding monomer.

[0040] In some embodiments, in the preparation method of the polymer shown in Formula V, the solvent may be a solvent commonly used in such reactions in the art. The solvent is preferably one or more of chlorinated hydrocarbon solvents, ether solvents, ester solvents, aromatic hydrocarbon solvents, and nitrile solvents. The chlorinated hydrocarbon solvent is preferably one or more of chloroform and dichloroethane. The ether solvent is preferably tetrahydrofuran. The ester solvent is preferably ethyl acetate. The aromatic hydrocarbon solvent is preferably toluene. The nitrile solvent is preferably one or more of benzonitrile and acetonitrile. The solvent is preferably a mixture of aromatic hydrocarbon solvents and nitrile solvents, more preferably a mixture of toluene and acetonitrile. In the mixture of aromatic hydrocarbon solvents and nitrile solvents, the volume ratio of the aromatic hydrocarbon solvent to the nitrile solvent is preferably 1:0.01-1:3; more preferably 1:1.

[0041] In some embodiments, in the method for preparing the polymer shown in Formula V, X is preferably a halogen. More preferably, it is Cl or Br. Even more preferably, it is Cl.

[0042] In some embodiments, in the method for preparing the polymer shown in Formula V, the quenching agent S7 is preferably methanol, a methanol solution of potassium hydroxide, or... More preferably, a methanol or a 0.5M methanol solution containing potassium hydroxide is preferred.

[0043] In some embodiments, in the method for preparing the polymer shown in Formula V, the... Preferred R 2 Methyl is preferred.

[0044] In some embodiments, in the method for preparing the polymer represented by Formula V, the molar ratio of the compound represented by Formula S6 to the compound represented by Formula Z6 can be conventional for such reactions in the art. Preferably, it is 1:5 to 1:20. More preferably, it is 1:10.

[0045] In some embodiments, in the method for preparing the polymer represented by Formula V, the molar volume ratio of the compound represented by Formula S6 to the quencher S7 can be conventional for such reactions in the art. Preferably, it is 1:15 mol / L to 4:15 mol / L. More preferably, it is 0.83:6 mol / L or 0.79:6 mol / L.

[0046] In some embodiments, in the method for preparing the polymer represented by Formula V, the molar volume ratio of the compound represented by Formula S6 to the solvent can be conventional for such reactions in the art. Preferably, it is 1:50 mol / L to 1:100 mol / L. More preferably, it is 0.83:50 mol / L or 0.79:50 mol / L.

[0047] In some embodiments, in the method for preparing the polymer shown in Formula V, the reaction temperature can be conventional for such reactions in the art. Preferably, it is 40-120°C. More preferably, it is 80°C.

[0048] In some embodiments, in the method for preparing the polymer shown in Formula V, the reaction time is preferably conventional for such reactions in the art, preferably 12-48 hours, and more preferably 24 hours.

[0049] In some embodiments, in the method for preparing the polymer shown in Formula V, the inert atmosphere can be conventional for such reactions in the art. A nitrogen atmosphere or an argon atmosphere is preferred.

[0050] In some embodiments, the preparation method of the polymer shown in Formula V may further include post-treatment. The post-treatment step is conventional for such reactions in the art. Preferably, the reaction product is distilled under reduced pressure, then the reaction product is precipitated in methanol, and the precipitate is dried under vacuum at 80°C.

[0051] In some embodiments, in the method for preparing the polymer represented by formula V, the solvent is benzonitrile; the polymer represented by formula S6 is... Compound Z6 It is 2-methyloxazoline; the quenching agent S7 is methanol; the polymer shown in formula V is

[0052] The compound represented by formula S6 and the compound represented by formula Z6 The molar ratio of the compound is 1:10; the molar volume ratio of the compound of formula S6 to the quenching reagent S7 is 0.83:6 mol / L; the molar volume ratio of the compound of formula S6 to the solvent is 0.83:50 mol / L; the reaction is carried out at a reaction temperature of 80°C; the reaction time is 24 hours; the reaction is carried out under a nitrogen atmosphere. The reaction is preferably post-treated as follows: the reaction product is distilled under reduced pressure, then the reaction product is precipitated in methanol, and then the precipitate is dried under vacuum at 80°C.

[0053] In some embodiments, in the method for preparing the polymer represented by formula V, the solvent is benzonitrile; the polymer represented by formula S6 is... Compound Z6 It is 2-methyloxazoline; the quenching agent S7 is a 0.5M methanol solution of potassium hydroxide; the polymer shown in formula V is The compound represented by formula S6 and the compound represented by formula Z6 The molar ratio of the compound is 1:10; the molar volume ratio of the compound of formula S6 to the quenching reagent S7 is 0.79:6 mol / L; the molar volume ratio of the compound of formula S6 to the solvent is 0.79:50 mol / L; the reaction is carried out at a reaction temperature of 80°C; the reaction time is 24 hours; the reaction is carried out under a nitrogen atmosphere. The reaction is preferably post-treated as follows: the reaction product is distilled under reduced pressure, then the reaction product is precipitated in methanol, and then the precipitate is dried under vacuum at 80°C.

[0054] In some embodiments, the preparation method of the polymer shown in Formula V further includes a preparation method of the polymer shown in S6, which includes the following steps: in an inert atmosphere, the polymer shown in Formula S4 and the compound shown in Formula S5 undergo an addition reaction as shown below in the presence of a catalyst to obtain the polymer shown in S6.

[0055]

[0056] Among them, R 1 R 1’ The definitions of Y, X, L and p are as described above.

[0057] In some embodiments, in the preparation method of the polymer shown in Formula S6, the catalyst can be conventional for such reactions in the art. Preferably, it is H2PtCl2 or a solution of platinum(O)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex. More preferably, the catalyst is a solution of platinum(O)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex.

[0058] In some embodiments, the reaction can be carried out in the presence of a solvent in the preparation method of the polymer shown in Formula S6.

[0059] In some embodiments, in the method for preparing the polymer shown in Formula S6, when the reaction can be carried out in the presence of a solvent, the solvent may be a solvent commonly used in such reactions in the art. The solvent is preferably one or more of chlorinated hydrocarbon solvents, ether solvents, ester solvents, aromatic hydrocarbon solvents, and nitrile solvents. The chlorinated hydrocarbon solvent is preferably one or more of chloroform and dichloroethane. The ether solvent is preferably tetrahydrofuran. The ester solvent is preferably ethyl acetate. The aromatic hydrocarbon solvent is preferably toluene. The nitrile solvent is preferably one or more of benzonitrile and acetonitrile. The solvent is preferably a mixture of aromatic hydrocarbon solvents and nitrile solvents, more preferably a mixture of toluene and acetonitrile. In the mixture of aromatic hydrocarbon solvents and nitrile solvents, the volume ratio of the aromatic hydrocarbon solvent to the nitrile solvent is preferably 1:0.01-1:3; more preferably 1:1.

[0060] In some embodiments, in the method for preparing the polymer shown in Formula S6, the molar ratio of S4 to S5 can be conventional for such reactions in the art. Preferably, it is 1:1 to 1:4. More preferably, it is 1:2.

[0061] In some embodiments, in the method for preparing the polymer represented by Formula S6, the molar volume ratio of S4 to the catalyst can be conventional for such reactions in the art. Preferably, it is 30:1 to 10:1. More preferably, it is 50:3.

[0062] In some embodiments, in the method for preparing the polymer shown in Formula S6, the reaction temperature can be conventional for such reactions in the art. Preferably, it is 60–80°C. More preferably, it is 60°C.

[0063] In some embodiments, in the method for preparing the polymer shown in Formula S6, the reaction time can be conventional for such reactions in the art. Preferably, it is 24 to 48 hours. More preferably, it is 48 hours.

[0064] In some embodiments, in the method for preparing the polymer shown in Formula S6, the inert atmosphere can be conventional for such reactions in the art. A nitrogen atmosphere and an argon atmosphere are preferred.

[0065] In some embodiments, in the method for preparing the polymer shown in Formula S6, the order of adding the reactants can be conventional for such reactions in the art. Preferably, S5 and S4 are mixed first, and then the catalyst is added.

[0066] In some embodiments, the preparation method of the polymer shown in Formula S6 may further include post-treatment. The post-treatment step is conventional for such reactions in the art. Preferably, the reaction product is cooled to room temperature, then dissolved in diethyl ether, filtered, solvent removed under reduced pressure, and dried under vacuum.

[0067] In some embodiments, in the method for preparing the polymer represented by formula S6, the compound represented by S4 is... The compound shown in S5 is The compound shown in S6 is The catalyst is a platinum(O)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution; the platinum content in the catalyst is preferably 2%; the inert atmosphere is nitrogen; the molar ratio of S4 to S5 is 1:2; the molar volume ratio of S4 to the catalyst is 50:3 mol / L; the reaction temperature is 60℃; the reaction time is 24 h; the order of addition is to first mix S5 and S4, then add the catalyst. After the reaction is complete, a post-treatment may be included. Preferably, the post-treatment step involves cooling the reaction product to room temperature, dissolving the product in diethyl ether, filtering, removing the solvent under reduced pressure, and vacuum drying.

[0068] In some embodiments, in the method for preparing the polymer represented by formula S6, the compound represented by S4 is... The compound shown in S5 is The compound shown in S6 is The catalyst is a platinum(O)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution; the platinum content in the catalyst is 2%; the inert atmosphere is nitrogen; the molar ratio of S4 to S5 is 1:2; the molar ratio of S4 to the catalyst is 50:3 mol / L; the reaction temperature is 60℃; the reaction time is 24 h; the order of addition is to first mix S5 and S4, then add the catalyst. After the reaction is complete, a post-treatment may be included. Preferably, the post-treatment step involves cooling the reaction product to room temperature, dissolving the product in diethyl ether, filtering, removing the solvent under reduced pressure, and vacuum drying.

[0069] This invention provides a polymer of formula S6:

[0070]

[0071] Among them, R 1 R 1’ The definitions of Y, X, L and p are as described above.

[0072] In some embodiments, the polymer shown in formula S6 is

[0073] In some embodiments, the polymer shown in formula S6 is

[0074] This invention provides a method for preparing the polymer shown in S6, comprising the following steps: In an inert atmosphere, the polymer shown in formula S4 and the compound shown in formula S5 undergo an addition reaction as shown below under the action of a catalyst to obtain the polymer shown in S6.

[0075]

[0076] Among them, R 1 R 1’ The definitions of Y, X, L and p, as well as the reaction conditions such as reaction temperature, reaction time, molar ratio of each reactant, and reaction operation are the same as described above.

[0077] Unless otherwise specified, the terms used in this invention have the following meanings:

[0078] The "-" at the end of a group indicates that the group is connected to the rest of the molecule through that site. For example, -CN refers to a cyano group.

[0079] The term "alkyl" refers to a saturated monovalent hydrocarbon group that has a specified number of carbon atoms, is straight-chain or branched. For example, C1-C6 alkyl groups include, but are not limited to: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, etc.

[0080] The term "alkoxy" refers to the group R. X -O-,R X The definition is the same as the term "alkyl". Alkoxy groups include, but are not limited to: methoxy, ethoxy, n-propoxy, isopropoxy, etc.

[0081] The term "alkylthio" refers to the group R. X -S-,R X The definition is the same as the term "alkyl". Alkylthio groups include, but are not limited to: methylthio, ethylthio, n-propylthio, isopropylthio, etc.

[0082] The term "aryl" refers to an aryl group having a specified number of carbon atoms (e.g., C6-C). 10 Aryl group is a cyclic, unsaturated monovalent hydrocarbon group, which can be monocyclic or polycyclic (e.g., two or three). In the case of polycyclic rings, the monocyclic rings share two atoms and one bond, and at least one ring is aromatic. The aryl group is attached to the rest of the molecule via an aromatic or non-aromatic ring. Aryl groups include, but are not limited to, phenyl, naphthyl, and... wait.

[0083] The term "heteroaryl" refers to a cyclic, unsaturated monovalent group having a specified number of ring atoms (e.g., 5-10), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatom (one or more of N, O, and S). It can be monocyclic or polycyclic, with the monocyclic rings sharing two atoms and one bond, and at least one ring is aromatic. Heteroaryl groups are attached to the rest of the molecule via carbon atoms or heteroatoms; they can be attached to the rest of the molecule via a ring with or without heteroatoms; or they can be attached to the rest of the molecule via an aromatic ring or a non-aromatic ring. Heteroaryl groups include, but are not limited to: wait.

[0084] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0085] The reagents and raw materials used in this invention are all commercially available.

[0086] The significant advantages of this invention are: the polymer can self-assemble into vesicle structures in solution, and the vesicles exhibit good stability. The preparation method described in this application features mild reaction conditions, fewer steps, reduced energy consumption, and optimized yield, achieving green synthesis of block copolymers. It further improves polymer yield and dispersibility, enables precise molecular weight control, and allows for diverse modification of end-capping groups and connecting groups between hydrophobic and hydrophilic blocks. Detailed Implementation

[0087] The purity and manufacturer information of each reagent in the example are as follows:

[0088]

[0089] Example 1: Synthesis of Triblock Polymer P1

[0090] The synthetic route for the triblock polymer P1 is as follows:

[0091]

[0092] Step 1, Synthesis of prepolymer S4-1: Under nitrogen protection, add 21 mL of S1 (0.956 g / mL, 296.62 g / mol, 67.68 mmol) to a Schlenk flask using a pipette, seal the flask with a rubber stopper, and then add 1.5 mL of 1,1,3,3-tetramethyldisiloxane S2 (0.76 g / mL, 134.33 g / mol, 8.49 mmol) using a syringe. The molar ratio of S1 to S2 is 8:1, with a slight excess of S1. Deoxygenate three times using argon gas. Heat to 55 °C, and then add 76.5 μL of trifluoromethanesulfonic acid S3 (1.696 g / mL, 150.08 g / mol, 0.86 mmol) using a microsyringe. React at 55 °C for 72 h. After the reaction was complete, the mixture was cooled to room temperature, and the product was dissolved in 200 ml of diethyl ether. The trifluoromethanesulfonic acid in the system was extracted multiple times with deionized water using a separatory funnel. Anhydrous magnesium sulfate was added and stirred for about 1 hour to remove water, followed by filtration. The diethyl ether was removed by rotary evaporation. The product was then dried under vacuum at 120 °C for about 8 hours to obtain the silane-hydrogen bond-terminated PDMS prepolymer S4 (18.7 g, yield 89%). Its structure and degree of polymerization were determined by integral of 1H NMR spectroscopy to be 30.0, as shown below.

[0093]

[0094] 1 ¹H NMR (500MHz, CDCl₃) δ 4.71–4.70 (m, 1H), 0.19–0.07 (m, 89.58H). The degree of polymerization of PDMS was calculated based on the H-NMR integral: 1 / 89.58 = 2 / (6n+12)n = 29.94, Mn = 2354 g / mol, PDI = 1.2.

[0095] Step 2, Synthesis of ClCH2C6H4CH2CH2-PDMS-CH2CH2C6H4CH2Cl prepolymer S6-1: Dry vinyl compound S5-1 (0.31 g, 152.62 g / mol, 2.0 mmol) was mixed with reactant S4-1 (2.2 g, 2220 g / mol, 1.0 mmol) in a reaction flask under nitrogen atmosphere. 60 μL of a platinum(O)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution (in xylene, Pt ~2%) was added. The reaction was carried out at 60 °C for 24 h. The reaction was confirmed to be complete by 1H NMR spectroscopy. After the reaction was complete, the mixture was cooled to room temperature, and the product was dissolved in 100 mL of diethyl ether and purified by filtration to remove residual catalyst. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to obtain benzyl chloride-terminated PDMS prepolymer S6-1 (2.1 g, 90% yield). Its structure and degree of polymerization were determined to be 30.0 by the integral of the 1H NMR spectrum.

[0096]

[0097] 1 H NMR (500MHz, CDCl3) δ 7.30-7.28 (m, 2.57H), 7.26-7.23 (m, 2.07H), 7.21-7.17 (m, 2.62H), 7.09-7.05 (m, 1.47H), 4.57-4.55 (m, 4.00H), 2.70-2.60 (m, 2.72H), 1.48-1.24 (m, 2.57H), 1.02-0.78 (m, 2.88H), 0.07 (s, 179.84H). Based on NMR calculations, the degree of polymerization is 4 / 179.84 = 4 / 6n, n = 29.97, Mn = 2525, and PDI = 1.2.

[0098] Step 3, Synthesis of Triblock MeO-PMOXA-PDMS-PMOXA-OMe (P1): Reactant S6-1 (2.1 g, 2525 g / mol, 0.83 mmol) and dried reactant S7-1 (0.7 g, 85.1 g / mol, 8.3 mmol) were dissolved in dried benzonitrile (50 mL) under nitrogen atmosphere and stirred at 80 °C for 48 h. After the reaction was complete, 6 mL of methanol was added, and the mixture was stirred at room temperature for 24 h. After the reaction was complete, benzonitrile and methanol were removed by vacuum distillation, and the precipitate was collected in 20 mL of methanol. The resulting polymer was dried under vacuum at 80 °C to obtain the triblock MeO-PMOXA-PDMS-PMOXA-OMe polymer P1 (3.8-30-3.8) (0.6 g, yield 22%).

[0099]

[0100] 1 ¹H NMR (500MHz, CDCl₃) δ 7.25–6.95 (m, 2.10H), 3.85–3.15 (m, 6.43H), 2.28–1.88 (m, 5.69H), 0.07 (s, 71.17H). Calculated from ¹H NMR integration, 5.69 / 1 = 6m / 4, m = 3.80, Mn = 3381, PDI = 1.2.

[0101] Example 2: Synthesis of Triblock Polymer P2

[0102] The synthetic route for the triblock polymer P2 is as follows:

[0103]

[0104] Step 1: Synthesis of H-PDMS-H prepolymer S4-2, as above. Take a dry Schlenk flask and replace the air in the reaction flask with N2 through a vacuum-nitrogen purging cycle. Then, under nitrogen purging, add 21 mL of octamethylcyclotetrasiloxane S1 (0.956 g / mL, 296.62 g / mol, 20.076 g, 67.68 mmol) and 1.2 mL of 1,1,3,3-tetramethyldisiloxane S2 (0.76 g / mL, 134.32 g / mol, 6.8 mmol) using a pipette, and stir to 55 °C. Then, pipette 77 μL of trifluoromethanesulfonic acid S3 (0.13 g, 1.696 g / mL, 0.865 mmol) into the above reaction flask, maintain the temperature at 55 °C, and react for 72 h. After the reaction was complete, the mixture was cooled to room temperature, and the product was dissolved in 200 ml of diethyl ether. The trifluoromethanesulfonic acid in the system was extracted multiple times with deionized water using a separatory funnel. Anhydrous magnesium sulfate was added and stirred for about 1 hour to remove water, followed by filtration. The diethyl ether was removed by rotary evaporation. The product was then dried under vacuum at 120 °C for about 8 hours to obtain the silane-hydrogen bond-terminated PDMS prepolymer S4 (18.5 g, yield 89%). Its structure and degree of polymerization were determined to be 47.8 by integrating the 1H NMR spectrum.

[0105] 1 H NMR (500MHz, CDCl3) δ4.71-4.70 (m, 1H), 0.07 (m, 176.56H).1 / 149.42=2 / (6n+12)n=47.8, Mn=3537g / mol, PDI=1.3.

[0106] Step 2, Synthesis of ClCH2C6H4CH2CH2-PDMS-CH2CH2C6H4CH2Cl prepolymer S6-2: Dry vinyl compound S5-1 (0.31 g, 152.62 g / mol, 2.0 mmol) was mixed with reactant S4-2 (3.5 g, 3537 g / mol, 1.0 mmol) in a reaction flask under nitrogen atmosphere. 60 μL of a platinum(O)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution (in xylene, Pt ~2%) was added. The reaction was carried out at 60 °C for 24 h. The reaction was confirmed to be complete by 1H NMR spectroscopy. After the reaction was complete, the mixture was cooled to room temperature, and the product was dissolved in 100 mL of diethyl ether and purified by filtration to remove residual catalyst. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to obtain benzyl chloride-terminated PDMS prepolymer S6-2 (3.0 g, yield 79%). Its structure and degree of polymerization were determined to be 47.03 by the integral of the 1H NMR spectrum.

[0107]

[0108] 1¹H NMR (500MHz, CDCl₃) δ 7.31-7.27 (m, 2.45H), 7.26-7.23 (m, 1.85H), 7.21-7.17 (m, 2.44H), 7.09-7.05 (m, 1.49H), 4.60-4.53 (m, 4.00H), 2.70-2.60 (m, 2.46H), 1.41-1.32 (m, 2.27H), 0.95-0.85 (m, 2.49H), 0.07 (s, 294.22H). Based on NMR calculations, the degree of polymerization is 4 / 294.22 = 4 / (6n+12), n = 47.03, Mn = 3782 g / mol, and PDI = 1.3.

[0109] Step 3, Synthesis of Triblock HO-PMOXA-PDMS-PMOXA-OH (P1): Reactant S6-2 (3.0 g, 3782 g / mol, 0.79 mmol) and dried reactant S7 (0.67 g, 85.1 g / mol, 7.9 mmol) were dissolved in 50 mL of dried benzonitrile under nitrogen atmosphere. The mixture was stirred at 80 °C for 48 h. After the reaction was complete, 6 mL of 0.5 mol / L KOH methanol solution was added, and the mixture was stirred at room temperature for 24 h. After the reaction was complete, benzonitrile and methanol were removed by vacuum distillation, and the precipitate was collected in 20 mL of methanol. The resulting polymer was dried under vacuum at 80 °C to obtain the triblock HO-PMOXA-PDMS-PMOXA-OH polymer P2 (5.41-47.0-5.41) (0.9 g, yield 23%).

[0110]

[0111] 1 ¹H NMR (500MHz, CDCl₃) δ 7.26–7.00 (m, 8.13H), 3.65–3.25 (m, 15.88H), 2.25–1.90 (m, 8.12H), 0.90–0.80 (m, 1.00H), 0.07 (m, 673.66H). Calculated from ¹H NMR integration, 8.12 / 1 = 6 m / 4, m = 5.41, Mn = 4957, PDI = 1.3.

[0112] Example 6: Preparation and Testing of Droplet Microfluidics from Triblock Polymer P5

[0113] Based on droplet microfluidics references:

[0114] 1)Janelle R.Anderson et al.Fabrication of Topologically ComplexThree-Dimensional Microfluidic Systems in PDMS by RapidPrototyping.Anal.Chem.2000,72,3158-3164;

[0115] 2)George M.Whitesides.The origins and the future ofmicrofluidics.Nature,2006,442,368-373.

[0116] The droplets of polymer P5 of this application were found to be stable for more than 30 minutes.

Claims

1. A method for preparing the polymer of formula V, comprising the following steps: in a solvent and under an inert atmosphere, reacting the polymer of formula S6, the compound of formula Z6, and the quenching reagent S7 as shown below to obtain the polymer of formula V. in, R is -OR t1 -NR t2 R t3 -COOMe, -(CH2) n1 SH, "5-10 membered heteroaryl groups substituted with 1, 2 or 3 oxy groups", -O(CH2) n2 OH or -OP(O)(OMe)O(CH2) n3 N + (Et)3, Among them, R t1 R t2 R t3 Independently H, Ts, C1-C6 alkyl, or -(CH2) n4 SH; n1, n3, and n4 are independently 0, 1, 2, 3, 4, 5, or 6; n2 is 2, 3, 4, 5, 6, 7, 8 or 9; L is , , , , , , , or , In the middle, R c It can be hydrogen, C1-C6 alkyl, C1-C6 alkoxy, -CN, or -NO2; In this context, n is 1, 2, 3, 4, 5, or 6; In this context, n is 3, 4, 5, 6, 7, 8, or 9; In the middle, R a (CH2) n n is 3, 4 or 5, R b It is hydrogen, C1-C6 alkyl or acetyl; 1 end and Connected; It is poly(2-methyloxazoline), polyphospholipid, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylamide, polymethyl methacrylate, poly(N,N-dimethylacrylamide), polyamide alkylene imide, polyhydroxyalkyl acrylate, poly(2-methyloxazoline) polyethylene glycol or poly(2-methyloxazoline) polyphospholipid. R 1 It is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C6-C 12 Aryl, -(CH2) n OH、 Or -(CH2) n -CH=CH2, where n is 3, 4 or 5; R 1’ It is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C6-C 12 Aryl, -(CH2) n OH、 Or -(CH2) n -CH=CH2, where n is 3, 4 or 5; Y is a C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, or C6-C 12 Aryl, -(CH2) n OH、 Or -(CH2) n -CH=CH2, where n is 3, 4 or 5; p is 20-50; X is a halogen, OTf, or OTs; The quenching reagent S7 is an inorganic alkali or RH; For polymer Corresponding monomers; In the 5-10 membered heteroaryl group, the number of heteroatoms is independently 1, 2 or 3, and the heteroatoms are independently selected from one or more of N, O and S.

2. The method for preparing the polymer of formula V as described in claim 1, characterized in that, The quenching agent S7 is KOH.

3. The method for preparing the polymer of formula V as described in claim 1, characterized in that, The preparation method satisfies one or more of the following conditions: a) The solvent is one or more of the following: chlorinated hydrocarbon solvents, ether solvents, ester solvents, aromatic hydrocarbon solvents, and nitrile solvents; b) The R 1 It is a C1-C6 alkyl group; c) The R 1’ It is a C1-C6 alkyl group; d) The Y is a C1-C6 alkyl group; e) The L is , Or -CH2-; f) The p value is 30-47; g) X is a halogen; h) The quenching reagent S7 is a methanol solution of potassium hydroxide or ; i) The above for R 2 It is methyl; j) The molar ratio of the compound shown in Formula S6 to the compound shown in Formula Z6 is 1:5-1:20; k) The molar volume ratio of the compound shown in formula S6 to the quenching reagent S7 is 1:15 mol / L-4:15 mol / L; l) The molar volume ratio of the compound shown in Formula S6 to the solvent is 1:50 mol / L - 1:100 mol / L; The reaction temperature described in m) is 40-120 ℃; The reaction time described in n) is 12-48 hours; o) The inert atmosphere is a nitrogen atmosphere or an argon atmosphere; p) also includes post-processing, wherein the post-processing step is vacuum distillation of the reaction product, followed by precipitation of the reaction product in methanol, and then placing the precipitate under vacuum at 80°C. o Dry at C.

4. The method for preparing the polymer of formula V as described in claim 3, characterized in that, The preparation method satisfies one or more of the following conditions: a) The chlorinated hydrocarbon solvent is one or more of chloroform and dichloroethane; b) The ether solvent is tetrahydrofuran; c) The ester solvent mentioned is ethyl acetate; d) The aromatic solvent mentioned is toluene; e) The nitrile solvent is one or more of benzonitrile and acetonitrile; f) The R 1 It is methyl; g) The R 1’ It is methyl; h) where Y is a methyl group; i) The L is ; j) The p is 30 or 47; k) X is Cl or Br; l) The quenching reagent S7 is methanol or a methanol solution with a potassium hydroxide concentration of 0.5M; The molar ratio of the compound shown in Formula S6 to the compound shown in Formula Z6 is 1:10; The molar volume ratio of the compound shown in formula S6 to the quenching reagent S7 is 0.83:6 mol / L or 0.79:6 mol / L; o) The molar volume ratio of the compound shown in formula S6 to the solvent is 0.83:50 mol / L or 0.79:50 mol / L; p) The reaction temperature is 80 °C; The reaction time described in q) is 24 hours.

5. The method for preparing the polymer of formula V as described in claim 3, characterized in that, The preparation method satisfies one or more of the following conditions: a) The solvent is a mixture of aromatic solvents and nitrile solvents; b) X is Cl.

6. The method for preparing the polymer of formula V as described in claim 5, characterized in that, The solvent is a mixture of toluene and acetonitrile.

7. The method for preparing the polymer of formula V as described in claim 3, characterized in that, The preparation method satisfies one or more of the following conditions: a) When the solvent is a mixture of aromatic solvent and nitrile solvent, the volume ratio of the aromatic solvent to the nitrile solvent in the mixture is 1:0.01-1:3; b) The above for , or , where each R 2 Each is independently a C1-C3 alkyl group; each m is independently an arbitrary value from 1 to 22; each w is independently an arbitrary value from 1 to 22; c) The R is hydroxyl, methoxy, TsO- or .

8. The method for preparing the polymer of formula V as described in claim 7, characterized in that, The preparation method satisfies one or more of the following conditions: a) The volume ratio of the aromatic solvent to the nitrile solvent is 1:1; b) The above In, each R 2 Each is independently a methyl group; c) In this context, each m is an independent value from 1 to 6. d) The above In this context, each w is an independent value from 1 to 6. e) The R is a hydroxyl or methoxy group.

9. The method for preparing the polymer of formula V as described in claim 8, characterized in that, The preparation method satisfies one or more of the following conditions: a) The above In this context, each m is independently 1, 1.1, 1.3, 3.6, 3.8, or 5.4; b) The above In this context, each w is independently 3.

10. The method for preparing the polymer of formula V as described in claim 9, characterized in that, The In this context, each m is independently 1, 1.1, 1.3, or 3.

6.

11. The method for preparing the polymer of formula V according to any one of claims 1-10, characterized in that, The preparation method further includes a method for preparing the polymer shown in formula S6, which includes the following steps: in an inert atmosphere, the polymer shown in formula S4 and the compound shown in formula S5 undergo an addition reaction as shown below in the presence of a catalyst to obtain the polymer shown in S6. Among them, R 1 R 1’ Y, X, L and p are defined as described in any one of claims 1-10.

12. The method for preparing the polymer of formula V as described in claim 11, characterized in that, The preparation method of the polymer shown in formula S6 satisfies one or more of the following conditions: a) The catalyst is H2PtCl2 or a solution of platinum(O)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex; b) The reaction is carried out in the presence of a solvent, which is one or more of chlorinated hydrocarbon solvents, ether solvents, ester solvents, aromatic hydrocarbon solvents, and nitrile solvents; c) The molar ratio of S4 to S5 is 1:1 to 1:4; d) The molar volume ratio of S4 to the catalyst is 30:1-10:1; e) The reaction temperature is 60~80°C. o C; f) The reaction time of the above reaction is 24~48 h; g) The inert atmosphere is a nitrogen atmosphere or an argon atmosphere; h) The reaction is carried out by first mixing S5 and S4, and then adding the catalyst; i) It also includes post-processing, wherein the post-processing steps are to cool the reaction product to room temperature, dissolve the reaction product in diethyl ether, filter, remove solvent under reduced pressure and dry under vacuum.

13. The method for preparing the polymer of formula V as described in claim 12, characterized in that, The preparation method of the polymer shown in formula S6 satisfies one or more of the following conditions: a) The catalyst is a solution of platinum(O)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex; b) The chlorinated hydrocarbon solvent is one or more of chloroform and dichloroethane; c) The ether solvent mentioned is tetrahydrofuran; d) The ester solvent mentioned is ethyl acetate; e) The aromatic hydrocarbons mentioned above are soluble in toluene; f) The nitrile solvent is one or more of benzonitrile and acetonitrile; g) The molar ratio of S4 to S5 is 1:2; h) The molar volume ratio of S4 to the catalyst is 50:3; i) The temperature of the reaction is 60°C. o C; j) The reaction time is 48 h.

14. The method for preparing the polymer of formula V as described in claim 13, characterized in that, The solvent is a mixture of aromatic solvents and nitrile solvents.

15. The method for preparing the polymer of formula V as described in claim 14, characterized in that, The solvent is a mixture of toluene and acetonitrile.

16. The method for preparing the polymer of formula V as described in claim 12, characterized in that, In the preparation method of the polymer shown in Formula S6, when the solvent is a mixture of aromatic solvent and nitrile solvent, the volume ratio of the aromatic solvent to the nitrile solvent in the mixture is 1:0.01-1:

3.

17. The method for preparing the polymer of formula V as described in claim 16, characterized in that, In the preparation method of the polymer shown in Formula S6, the volume ratio of the aromatic solvent and the nitrile solvent is 1:

1.

18. A polymer of formula S6: in, R 1 R 1’ Y, X, L and p are defined as described in any one of claims 1-10.

19. The polymer of formula S6 as described in claim 18, characterized in that, The polymer represented by formula S6 is any of the following polymers: or .

20. A method for preparing a polymer of formula S6, comprising the following steps: in an inert atmosphere, performing an addition reaction as shown below on the polymer of formula S4 and the compound of formula S5 in the presence of a catalyst to obtain the polymer of formula S6. in, R 1 R 1’ Y, X, L and p are defined as described in claim 11, and the reaction conditions are as described in any one of claims 12-17.

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