Preparation method of amphiphilic polymer

Abstract

The invention provides a preparation method of an amphiphilic polymer. The invention discloses a preparation method of a polymer as shown in a formula V. The preparation method comprises the following step: in a solvent and in an inert atmosphere, carrying out a reaction as shown in the specification on a polymer as shown in a formula S6, a compound as shown in a formula Z6 and a quenching reagent S7 to prepare the polymer as shown in the formula V. When the polymer shown in the formula V is prepared by using the method, the reaction conditions are mild, the working procedures are reduced, the energy consumption is reduced, the yield is optimized, and green synthesis of the block copolymer is realized. # imgabs0 #

Description

A method for preparing amphiphilic polymer Technical Field

[0001] The invention relates to a preparation method of an amphiphilic polymer and belongs to the field of polymers. Background Art

[0002] Self-assembly at the nanoscale is a key property that nature relies on to generate biological membranes. These membranes construct a functional molecular framework by embedding channels, receptors, and molecular pumps within a microenvironmental and functional framework. Leveraging hydrophobic-hydrophilic interactions, these membranes self-assemble into bilayers, vesicles, and other structures. Self-assembled membranes are a key component if we hope to mimic the principles of natural nanostructures. In recent years, a range of polymer systems have been exploited 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 to form micelles, worm-like micelles, tubular structures, membranes, or vesicles.

[0003] While a wide variety of block copolymer structures exist, ABA triblock copolymers have garnered particular attention in recent years due to their inherent ability to self-assemble into vesicular structures, despite their highly hydrophobic and hydrophilic nature. From a biomedical perspective, polyoxazolines, which offer a pseudopolypeptide architecture, are particularly attractive and have been chosen as the hydrophilic block A. Polymethylsiloxane (PDMS), due to the ionic nature of its Si-CH3 bonds, exhibits a very low glass transition temperature and is generally liquid at room temperature. Furthermore, poly(siloxanes) have very low surface energy and are extremely hydrophobic; therefore, they have been chosen as the hydrophobic block B. This class of ABA triblock copolymer systems has been extensively studied and demonstrated to possess interesting biomedical and self-assembly properties.

[0004] Existing synthesis methods, through a core-first synthesis strategy, have constructed a series of ABA triblock backbone polymers, but they have disadvantages such as many synthesis steps, low yield, high polymer dispersibility, poor reproducibility, and difficulty in modifying the molecular structure.

[0005] Summary of the Invention

[0006] The technical problem to be solved by the present invention is that existing methods for synthesizing block copolymers have multiple synthesis steps, involve unstable metallic lithium reagents, highly toxic reagents such as pyridine, and have disadvantages such as low yield, high polymer dispersibility, poor reproducibility, and difficulty in modifying the molecular structure. To this end, the present invention provides a method for preparing an amphiphilic polymer.

[0007] The present invention provides a polymer represented by formula V:

[0008]

[0009] in,

[0010] The R is -OR t1 、-NR t2 R t3 、-COOMe、-(CH2) n1 SH, 5-10 membered heteroaryl substituted by 1, 2 or 3 oxo groups, -O(CH2) n2 OH, -OP(O)(OMe), -OP(O)(OMe)(O(CH2) n3 N + (Et)3,

[0011] Among them, the R t1 、R t2 、R t3 are independently H, Ts, C1-C6 alkyl or -(CH2) n4 SH;

[0012] n1, n3 and n4 are independently 0, 1, 2, 3, 4, 5 or 6;

[0013] n2 is 2, 3, 4, 5, 6, 7, 8 or 9;

[0014] The L is

[0015] described In the R c is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, -CN or -NO2;

[0016] described In, n is 1, 2, 3, 4, 5 or 6;

[0017] described In, n is 3, 4, 5, 6, 7, 8 or 9;

[0018] described In the R a (CH2) n , n is 3, 4 or 5, said R b is hydrogen, C1-C6 alkyl or acetyl;

[0019] The 1 end and the connected;

[0020] described It is poly-2-methyloxazoline, polyphospholipid, polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylamide, polymethyl methacrylate, poly(N,N-dimethylacrylamide), polyacylalkylene imine, polyhydroxyalkyl acrylate, poly-2-methyloxazoline polyethylene glycol or poly-2-methyloxazoline polyphospholipid;

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

[0022] The R 1’ C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5;

[0023] The Y is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C6-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5;

[0024] Said p is 20-50;

[0025] 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.

[0026] In some embodiments, the Preferably Among them, each R 2 Each is independently a C1-C3 alkyl group, preferably a methyl group; 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; further 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.

[0027] In some embodiments, the Preferably

[0028] In some embodiments, the R 1 It is preferably a C1-C6 alkyl group, and more preferably a methyl group.

[0029] In some embodiments, the R 1’ It is preferably a C1-C6 alkyl group, and more preferably a methyl group.

[0030] In some embodiments, Y is preferably a C1-C6 alkyl group, more preferably a methyl group.

[0031] In some embodiments, the R is preferably hydroxy, methoxy, TsO- or More preferred is a hydroxy group or a methoxy group.

[0032] In some embodiments, the L is preferably Or -CH2-. More preferably

[0033] In some embodiments, the p is preferably any value between 20 and 47, more preferably 30 or 47.

[0034] In some embodiments, the R 1 Preferably methyl; said R 1’ Preferably methyl; Preferably The R 2 Preferably, it is methyl; R is preferably methoxy; Y is preferably methyl; L is preferably The m is preferably 3.8; the p is preferably 30.

[0035] In some embodiments, the R 1 Preferably methyl; said R 1’ Preferably methyl; Preferably The R 2 Preferably, it is methyl; R is preferably hydroxy; Y is preferably methyl; L is preferably The m is preferably 5.4; the p is preferably 47.

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

[0037] In some embodiments, the polymer represented by formula V is

[0038] The present invention provides a method for preparing a polymer represented by V, comprising the following steps: in a solvent and in an inert atmosphere, reacting a polymer represented by formula S6, a compound represented by formula Z6, and a quenching reagent S7 as shown below to obtain a polymer represented by formula V,

[0039]

[0040] Wherein, the R, L, R 1 、R 1’ , Y, and p are as defined above; X is a halogen, OTf, or OTs; the quenching reagent S7 is an inorganic base (eg, KOH) or RH, and R is as defined above; For polymer The corresponding monomer.

[0041] In some embodiments, in the method for preparing the polymer represented by Formula V, the solvent may be a commonly used solvent for such reactions in the art. The solvent is preferably one or more of a chlorinated hydrocarbon solvent, an ether solvent, an ester solvent, an aromatic hydrocarbon solvent, and a nitrile solvent. 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 mixed solvent of an aromatic hydrocarbon solvent and a nitrile solvent, more preferably a mixed solvent of toluene and acetonitrile. In the mixed solvent of the aromatic hydrocarbon solvent and the nitrile solvent, the volume ratio of the aromatic hydrocarbon solvent to the nitrile solvent is preferably 1:0.01-1:3; more preferably 1:1.

[0042] In some embodiments, in the method for preparing the polymer represented by Formula V, X is preferably halogen, more preferably Cl or Br, and even more preferably Cl.

[0043] In some embodiments, in the method for preparing the polymer of formula V, the quenching reagent S7 is preferably methanol, a methanol solution of potassium hydroxide or More preferred is methanol or a methanol solution with a potassium hydroxide concentration of 0.5 M.

[0044] In some embodiments, in the method for preparing the polymer of formula V, Preferably R 2 Preferred is methyl.

[0045] In some embodiments, in the method for preparing the polymer of Formula V, the molar ratio of the compound of Formula S6 to the compound of Formula Z6 can be conventional in the art for such reactions, preferably 1:5-1:20, more preferably 1:10.

[0046] In some embodiments, in the method for preparing the polymer of Formula V, the molar volume ratio of the compound of Formula S6 to the quenching reagent S7 can be conventional in the art for such reactions, preferably 1:15 mol / L to 4:15 mol / L, and more preferably 0.83:6 mol / L or 0.79:6 mol / L.

[0047] In some embodiments, in the method for preparing the polymer of Formula V, the molar volume ratio of the compound of Formula S6 to the solvent can be conventional in the art for such reactions, preferably 1:50 mol / L to 1:100 mol / L, more preferably 0.83:50 mol / L or 0.79:50 mol / L.

[0048] In some embodiments, in the method for preparing the polymer represented by Formula V, the reaction temperature may be conventional for such reactions in the art, preferably 40-120°C, more preferably 80°C.

[0049] In some embodiments, in the method for preparing the polymer of Formula V, the reaction time is preferably 12-48 hours, more preferably 24 hours, whichever is conventional in the art for such reactions.

[0050] In some embodiments, in the method for preparing the polymer represented by Formula V, the inert atmosphere may be any conventional inert atmosphere for such reactions in the art, preferably a nitrogen atmosphere or an argon atmosphere.

[0051] In some embodiments, the method for preparing the polymer of Formula V may further include post-treatment. The post-treatment steps may be conventional in the art for such reactions. Preferably, the reaction product is distilled under reduced pressure, precipitated in methanol, and then dried in a vacuum at 80°C.

[0052] In some embodiments, in the method for preparing the polymer of formula V, the solvent is benzonitrile; the polymer of formula S6 is Compound represented by formula Z6 is 2-methyloxazoline; the quenching reagent S7 is methanol; the polymer represented by formula V is

[0053] The compound represented by formula S6 and the compound represented by formula Z6 The molar ratio of the compound represented by Formula S6 to the quenching reagent S7 is 1:10; the molar volume ratio of the compound represented by Formula S6 to the quenching reagent S7 is 0.83:6 mol / L; the molar volume ratio of the compound represented by 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; and 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, the reaction product is precipitated in methanol, and the precipitate is then dried in a vacuum at 80°C.

[0054] In some embodiments, in the method for preparing the polymer of formula V, the solvent is benzonitrile; the polymer of formula S6 is Compound represented by formula Z6 is 2-methyloxazoline; the quenching reagent S7 is a methanol solution with a potassium hydroxide concentration of 0.5M; the polymer represented by formula V is The compound represented by formula S6 and the compound represented by formula Z6 The molar ratio of the compound represented by Formula S6 to the quenching reagent S7 is 1:10; the molar volume ratio of the compound represented by Formula S6 to the quenching reagent S7 is 0.79:6 mol / L; the molar volume ratio of the compound represented by Formula S6 to the solvent is 0.79:50 mol / L; the reaction is carried out at a temperature of 80°C; the reaction time is 24 hours; and the reaction is carried out under a nitrogen atmosphere. The reaction is preferably post-processed by distilling the reaction product under reduced pressure, precipitating the reaction product in methanol, and then drying the precipitate in a vacuum at 80°C.

[0055] In some embodiments, the method for preparing the polymer represented by formula V further includes a method for preparing the polymer represented by formula S6, which comprises the following steps: in an inert atmosphere, subjecting the polymer represented by formula S4 and the compound represented by formula S5 to an addition reaction as shown below in the presence of a catalyst to obtain the polymer represented by formula S6.

[0056]

[0057] Among them, R 1 、R 1’ , Y, X, L and p are defined as above.

[0058] In some embodiments, in the method for preparing the polymer represented by formula S6, the catalyst can be any conventional catalyst in the art for such reactions. Preferably, it is H2PtCl2 or a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution. More preferably, the catalyst is a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution.

[0059] In some embodiments, in the method for preparing the polymer represented by formula S6, the reaction can be carried out in the presence of a solvent.

[0060] In some embodiments, in the method for preparing the polymer represented by formula S6, when the reaction can be carried out in the presence of a solvent, the solvent can be a commonly used solvent for such reactions in the art. The solvent is preferably one or more of a chlorinated hydrocarbon solvent, an ether solvent, an ester solvent, an aromatic hydrocarbon solvent, and a nitrile solvent. 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 mixed solvent of an aromatic hydrocarbon solvent and a nitrile solvent, more preferably a mixed solvent of toluene and acetonitrile. In the mixed solvent of the aromatic hydrocarbon solvent and the nitrile solvent, the volume ratio of the aromatic hydrocarbon solvent to the nitrile solvent is preferably 1:0.01-1:3; more preferably 1:1.

[0061] In some embodiments, in the method for preparing the polymer represented by formula S6, the molar ratio of S4 to S5 can be conventional in the art for such reactions, preferably 1:1 to 1:4, and more preferably 1:2.

[0062] 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 in the art for such reactions, preferably 30:1 to 10:1, and more preferably 50:3.

[0063] In some embodiments, in the method for preparing the polymer represented by formula S6, the reaction temperature can be conventional for such reactions in the art, preferably 60 to 80°C, more preferably 60°C.

[0064] In some embodiments, in the method for preparing the polymer represented by formula S6, the reaction time can be conventional for such reactions in the art, preferably 24 to 48 hours, more preferably 48 hours.

[0065] In some embodiments, in the method for preparing the polymer represented by formula S6, the inert atmosphere can be any conventional inert atmosphere for such reactions in the art, preferably nitrogen atmosphere or argon atmosphere.

[0066] In some embodiments, in the method for preparing the polymer represented by formula S6, the order of adding the materials for the reaction can be conventional in the art for such reactions. Preferably, S5 and S4 are mixed first, and then the catalyst is added.

[0067] In some embodiments, the method for preparing the polymer of formula S6 may further include post-treatment. The post-treatment step may be conventional in the art for such reactions. Preferably, the reaction product is cooled to room temperature, then dissolved in diethyl ether, filtered, desolvated under reduced pressure, and vacuum dried.

[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 (0)-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°C; the reaction time is 24 hours; the order of adding the materials to the reaction is to first mix S5 and S4, and then add the catalyst. After the reaction is completed, post-processing may also be included. The post-processing step preferably involves cooling the reaction product to room temperature, dissolving the reaction product in ether, filtering, removing the solvent under reduced pressure, and vacuum drying.

[0069] 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 (0)-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°C; the reaction time is 24 hours; and the order of adding the materials is to first mix S5 and S4, and then add the catalyst. After completion of the reaction, post-processing may also be included. The post-processing step preferably involves cooling the reaction product to room temperature, dissolving the reaction product in ether, filtering, removing the solvent under reduced pressure, and vacuum drying.

[0070] The present invention provides a polymer represented by formula S6:

[0071]

[0072] Among them, R 1 、R 1’ , Y, X, L and p are defined as above.

[0073] In some embodiments, the polymer represented by formula S6 is

[0074] In some embodiments, the polymer represented by formula S6 is

[0075] The present invention provides a method for preparing a polymer represented by S6, comprising the following steps: in an inert atmosphere, subjecting a polymer represented by formula S4 and a compound represented by formula S5 to an addition reaction as shown below in the presence of a catalyst to obtain a polymer represented by S6.

[0076]

[0077] Among them, R 1 、R 1’ The definitions of Y, X, L and p and the reaction conditions such as reaction temperature, reaction time, molar ratio of each reactant, reaction operation, etc. are the same as described above.

[0078] Unless otherwise specified, the terms used in this invention have the following meanings:

[0079] A "-" at the end of a group indicates that the group is attached to the rest of the molecule through that site. For example, -CN refers to a cyano group.

[0080] The term "alkyl" refers to a linear or branched, saturated, monovalent hydrocarbon radical having a specified number of carbon atoms. For example, C1-C6 alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and the like.

[0081] The term "alkoxy" refers to a group R X -O-, R X The same definition as the term "alkyl". Alkoxy includes, but is not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, and the like.

[0082] The term "alkylthio" refers to a group R X -S-, R X The same definition as the term "alkyl". Alkylthio includes, but is not limited to, methylthio, ethylthio, n-propylthio, isopropylthio, and the like.

[0083] The term "aryl" refers to a group having the specified number of carbon atoms (e.g., C6-C 10 ) cyclic, unsaturated monovalent hydrocarbon group, which is monocyclic or polycyclic (for example, 2 or 3), in the case of polycyclic, the monocyclics share two atoms and one bond, and at least one ring is aromatic. The aryl group is connected to the rest of the molecule through an aromatic ring or a non-aromatic ring. Aryl groups include but are not limited to: phenyl, naphthyl, wait.

[0084] The term "heteroaryl" refers to a cyclic, unsaturated, monovalent group having a specified number of ring atoms (e.g., 5-10 members), a specified number of heteroatoms (e.g., 1, 2, or 3), a specified type of heteroatom (one or more of N, O, and S), which is monocyclic or polycyclic, with two atoms and one bond shared between the rings, and at least one ring being aromatic. A heteroaryl group is attached to the rest of the molecule through a carbon atom or a heteroatom; a heteroaryl group is attached to the rest of the molecule through a ring that has heteroatoms or a ring that does not have heteroatoms; a heteroaryl group is attached to the rest of the molecule through a ring that is aromatic or a ring that is not aromatic. Heteroaryl groups include, but are not limited to: wait.

[0085] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0086] The reagents and raw materials used in the present invention are commercially available.

[0087] The positive advances of the present invention include: the polymer can self-assemble into vesicle structures in solution, and the vesicles have good stability. The preparation method of the present invention has mild reaction conditions, reduced process steps, reduced energy consumption, and optimized yield, achieving green synthesis of block copolymers, further improving polymer yield and dispersibility, and enabling precise molecular weight control and diversified modification of end-capping groups and the linking groups between the hydrophobic and hydrophilic blocks. DETAILED DESCRIPTION

[0088] The purity and manufacturer information of each reagent in the examples are as follows:

[0089]

[0090] Example 1 Synthesis of triblock polymer P1

[0091] The synthesis route of triblock polymer P1 is as follows:

[0092]

[0093] Step 1, Synthesis of Prepolymer S4-1: Under nitrogen, pipette 21 mL of S1 (0.956 g / mL, 296.62 g / mol, 67.68 mmol) into a Schlenk flask. Seal the top with a rubber stopper. Then, add 1.5 mL of 1,1,3,3-tetramethyldisiloxane S2 (0.76 g / mL, 134.33 g / mol, 8.49 mmol) via syringe. The molar ratio of S1 to S2 is 8:1. A slight excess of S1 is acceptable. Deoxygenate with argon three times. Raise the temperature to 55°C, then add 76.5 μL of trifluoromethanesulfonic acid S3 (1.696 g / mL, 150.08 g / mol, 0.86 mmol) via microinjector. Reaction at 55°C for 72 h. After the reaction was completed, the product was cooled to room temperature and dissolved in 200 ml of diethyl ether. Trifluoromethanesulfonic acid was extracted multiple times with deionized water in a separatory funnel. Anhydrous magnesium sulfate was added and stirred for approximately 1 hour to remove moisture, followed by filtration. The diethyl ether was removed by rotary evaporation. Drying was performed under vacuum at 120°C for approximately 8 hours to obtain Si-H bond-terminated PDMS prepolymer S4 (18.7 g, 89% yield). Its structure and degree of polymerization (DP) were determined to be 30.0 by integrating the H NMR spectrum, as shown below.

[0094]

[0095] 1 H NMR (500 MHz, CDCl3) δ 4.71-4.70 (m, 1H), 0.19-0.07 (m, 89.58H). The PDMS degree of polymerization was calculated based on H-NMR integration: 1 / 89.58 = 2 / (6n+12)n = 29.94, Mn = 2354 g / mol, and PDI = 1.2.

[0096] 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) and reaction material S4-1 (2.2 g, 2220 g / mol, 1.0 mmol) were mixed in a reaction flask under nitrogen, and 60 μL of platinum (0)-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. H NMR spectroscopy confirmed the completion of the reaction. After the reaction was complete, the mixture was cooled to room temperature, the product was dissolved in 100 ml of diethyl ether, and filtered 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 H-NMR spectrum integration.

[0097]

[0098] 1 H NMR (500 MHz, 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). The degree of polymerization was calculated based on NMR: 4 / 179.84 = 4 / 6n, n = 29.97, Mn = 2525, and PDI = 1.2.

[0099] Step 3, Synthesis of Triblock MeO-PMOXA-PDMS-PMOXA-OMe (P1): Reaction material S6-1 (2.1 g, 2525 g / mol, 0.83 mmol) and dried reaction material S7-1 (0.7 g, 85.1 g / mol, 8.3 mmol) were dissolved in dry benzonitrile (50 mL) under nitrogen and stirred at 80°C for 48 h. After the reaction was complete, 6 mL of methanol was added and stirred at room temperature for 24 h. After the reaction, benzonitrile and methanol were removed by vacuum distillation, and the mixture was precipitated in 20 mL of methanol. The resulting polymer was dried under vacuum at 80°C to obtain triblock MeO-PMOXA-PDMS-PMOXA-OMe polymer P1 (3.8-30-3.8) (0.6 g, 22% yield).

[0100]

[0101] 1 H NMR (500 MHz, 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 based on H-NMR integration, 5.69 / 1 = 6m / 4, m = 3.80, Mn = 3381, PDI = 1.2.

[0102] Example 2 Synthesis of triblock polymer P2

[0103] The synthesis route of triblock polymer P2 is as follows:

[0104]

[0105] 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 cycle. Then, under nitrogen flow, 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. Stir and heat to 55°C. 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 hours. After the reaction is complete, cool to room temperature and dissolve the product in 200 ml of ether. Extract the trifluoromethanesulfonic acid in the system with deionized water several times in a separatory funnel. Add anhydrous magnesium sulfate and stir for about 1 hour to remove moisture. Filter. Remove the ether by rotary evaporation. Dry under vacuum at 120°C for about 8 hours to obtain Si-H bond-terminated PDMS prepolymer S4 (18.5 g, 89% yield). Its structure and degree of polymerization were determined by H NMR spectrum integration to be 47.8.

[0106] 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.

[0107] 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) and reaction material S4-2 (3.5 g, 3537 g / mol, 1.0 mmol) were mixed in a reaction flask under nitrogen, and 60 μL of platinum (0)-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. H NMR spectroscopy confirmed the completion of the reaction. After the reaction was complete, the mixture was cooled to room temperature, the product was dissolved in 100 ml of diethyl ether, and filtered 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, 79% yield). Its structure and degree of polymerization were determined to be 47.03 by H-NMR spectrum integration.

[0108]

[0109] 1H NMR (500 MHz, 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). The degree of polymerization was calculated based on NMR: 4 / 294.22 = 4 / (6n+12), n = 47.03, Mn = 3782 g / mol, and PDI = 1.3.

[0110] Step 3, Synthesis of Triblock HO-PMOXA-PDMS-PMOXA-OH (P1): The starting material S6-2 (3.0 g, 3782 g / mol, 0.79 mmol) and the dried starting material S7 (0.67 g, 85.1 g / mol, 7.9 mmol) were dissolved in dry benzonitrile (50 mL) under nitrogen and 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 stirred at room temperature for 24 h. After the reaction was completed, the benzonitrile and methanol were removed by vacuum distillation, and the product was precipitated 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, 23% yield).

[0111]

[0112] 1 H NMR (500 MHz, 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 based on H-NMR integration, 8.12 / 1 = 6m / 4, m = 5.41, Mn = 4957, PDI = 1.3.

[0113] Example 6 Preparation and Testing of Droplet Microfluidics of Triblock Polymer P5

[0114] According to the droplet microfluidics reference:

[0115] 1)Janelle R.Anderson et al.Fabrication of Topologically Complex Three-Dimensional Microfluidic Systems in PDMS by Rapid Prototyping.Anal.Chem.2000,72,3158-3164;

[0116] 2) George M. Whitesides. The origins and the future of microfluidics. Nature, 2006, 442, 368-373.

[0117] It was measured that the droplets of the polymer P5 of the present application can exist stably for more than 30 minutes.

Claims

1. A method for preparing a polymer of formula V, comprising the following steps: in a solvent, under an inert atmosphere, reacting a polymer of formula S6, a compound of formula Z6, and a quenching agent S7 as shown below to obtain a polymer of formula V. in, The R is -OR t1 、-NR t2 R t3 、-COOMe、-(CH2) n1 SH, 5-10 membered heteroaryl substituted by 1, 2 or 3 oxo groups, -O(CH2) n2 OH, -OP(O)(OMe), -OP(O)(OMe)(O(CH2) n3 N + (Et)3, Among them, the R t1 、R t2 、R t3 are 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; The L is described In the R c is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, -CN or -NO2; described In, n is 1, 2, 3, 4, 5 or 6; described In, n is 3, 4, 5, 6, 7, 8 or 9; described In the R a (CH2) n , n is 3, 4 or 5, said R b is hydrogen, C1-C6 alkyl or acetyl; The 1 end and the connected; described It is poly-2-methyloxazoline, polyphospholipid, polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylamide, polymethyl methacrylate, poly(N,N-dimethylacrylamide), polyacylalkylene imine, polyhydroxyalkyl acrylate, poly-2-methyloxazoline polyethylene glycol or poly-2-methyloxazoline polyphospholipid; The R 1 C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5; The R 1’ C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5; The Y is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C6-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5; Said p is 20-50; X is halogen, OTf or OTs; The quenching reagent S7 is an inorganic base (such as KOH) or RH; described For polymer The corresponding monomer; 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 according to claim 1, wherein The preparation method satisfies one or more of the following conditions: a) the solvent is preferably one or more of a chlorinated hydrocarbon solvent, an ether solvent, an ester solvent, an aromatic hydrocarbon solvent and a nitrile solvent; 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 more preferably a mixed solvent of an aromatic hydrocarbon solvent and a nitrile solvent, and further preferably a mixed solvent of toluene and acetonitrile; b) the R 1 Preferably C1-C6 alkyl; more preferably methyl; c) the R 1’ Preferably C1-C6 alkyl; more preferably methyl; d) Y is preferably a C1-C6 alkyl group; more preferably a methyl group; e) L is preferably or -CH2-; more preferably f) p is preferably 30-47; more preferably 30 or 47; g) X is preferably halogen; more preferably Cl or Br; further preferably Cl; h) The quenching reagent S7 is preferably a methanol solution of potassium hydroxide or More preferably, methanol or a methanol solution with a potassium hydroxide concentration of 0.5 M; i) Preferably R 2 Preferably methyl; j) The molar ratio of the compound represented by formula S6 to the compound represented by formula Z6 is preferably 1:5-1:20; more preferably 1:10; k) The molar volume ratio of the compound represented by formula S6 to the quenching reagent S7 is preferably 1:15 mol / L-4:15 mol / L; more preferably 0.83:6 mol / L or 0.79:6 mol / L; 1) The molar volume ratio of the compound represented by formula S6 to the solvent is preferably 1:50 mol / L-1:100 mol / L; more preferably 0.83:50 mol / L or 0.79:50 mol / L; m) the reaction temperature is preferably 40-120°C; more preferably 80°C; n) the reaction time is selected from 12 to 48 hours; more preferably 24 hours; o) the inert atmosphere is preferably a nitrogen atmosphere or an argon atmosphere; p) further comprises post-treatment, wherein the post-treatment step preferably comprises distilling the reaction product under reduced pressure, precipitating the reaction product in methanol, and then drying the precipitate in a vacuum at 80°C.

3. The method for preparing the polymer of formula V according to claim 2, wherein: The preparation method satisfies one or more of the following conditions: a) when the solvent is a mixed solvent of an aromatic hydrocarbon solvent and a nitrile solvent, the volume ratio of the aromatic hydrocarbon solvent to the nitrile solvent in the mixed solvent is 1:0.01-1:3; preferably 1:1; b) for Among them, each R 2 Each is independently a C1-C3 alkyl group, preferably a methyl group; each m is independently any number from 1 to 22; preferably any number from 1 to 6; more preferably 1, 1.1, 1.3, 3.6, 3.8 or 5.4; further preferably 1, 1.1, 1.3 or 3.6; each w is independently any number from 1 to 22; preferably any number from 1 to 6; more preferably 3; c) R is preferably hydroxyl, methoxy, TsO- or More preferably hydroxy or methoxy; d) The polyoxazoline polymer is preferably poly-2-methyloxazoline.

4. The method for preparing a polymer of formula V according to any one of claims 1 to 3, wherein: The preparation method also includes a preparation method of a polymer represented by formula S6, which comprises the following steps: in an inert atmosphere, subjecting the polymer represented by formula S4 and the compound represented by formula S5 to an addition reaction as shown below under the action of a catalyst to obtain the polymer represented by formula S6. Among them, R 1 、R 1’ , Y, X, L and p are as defined in any one of claims 1-3.

5. The method for preparing the polymer of formula V according to claim 4, wherein: The preparation method of the polymer represented by formula S6 satisfies one or more of the following conditions: a) The catalyst is preferably H2PtCl2 or a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution; more preferably a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution; b) the reaction is carried out in the presence of a solvent, wherein the solvent is preferably one or more of a chlorinated hydrocarbon solvent, an ether solvent, an ester solvent, an aromatic hydrocarbon solvent and a nitrile solvent; 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 more preferably a mixed solvent of an aromatic hydrocarbon solvent and a nitrile solvent, and further preferably a mixed solvent of toluene and acetonitrile; c) the molar ratio of S4 to S5 is preferably 1:1-1:4; more preferably 1:2; d) the molar volume ratio of the S4 to the catalyst is preferably 30:1-10:1; more preferably 50:3; e) the reaction temperature is preferably 60-80°C; more preferably 60°C; f) The reaction time of the reaction is preferably 24 to 48 hours; more preferably 48 hours; g) The inert atmosphere is preferably a nitrogen atmosphere or an argon atmosphere; h) The order of adding materials for the reaction is preferably to mix S5 and S4 first, and then add the catalyst; i) also includes post-treatment, wherein the post-treatment step preferably comprises cooling the reaction product to room temperature, dissolving the reaction product in ether, filtering, removing the solvent under reduced pressure, and vacuum drying.

6. The method for preparing the polymer of formula V according to claim 5, wherein: In the preparation method of the polymer represented by formula S6, when the solvent is a mixed solvent of an aromatic hydrocarbon solvent and a nitrile solvent, the volume ratio of the aromatic hydrocarbon solvent to the nitrile solvent in the mixed solvent is 1:0.01-1:3; preferably 1:

1.

7. A polymer represented by formula S6: in, R 1 、R 1’ , Y, X, L and p are defined as described in any one of claims 1 to 3; the polymer represented by formula S6 is preferably any one of the following polymers:

8. A method for preparing a polymer of formula S6, comprising the steps of: in an inert atmosphere, subjecting a polymer of formula S4 and a compound of formula S5 to an addition reaction as shown below in the presence of a catalyst to obtain a polymer of formula S6. in, R 1 、R 1’ , Y, X, L and p are as defined in claim 4, and the reaction conditions are as described in claim 5 or 6.

Images