Temperature-sensitive catalyst for coupling reaction, and preparation method and application thereof

Abstract

The application provides a temperature-sensitive catalyst for a coupling reaction and a preparation method and application thereof, and belongs to the technical field of catalyst preparation for a coupling reaction, and the specific steps include: mixing and reacting polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate, a nitrogen-phosphorus monomer and an auxiliary agent to generate a copolymer, and then complexing the copolymer with a palladium compound to obtain the temperature-sensitive catalyst. The catalyst is complexed by a copolymer of three monomers and a palladium compound. The polyethylene glycol methyl ether methacrylate unit is used to ensure the temperature sensitivity of the whole catalyst structure; the small-molecule nitrogen-phosphorus ligand and the organic amine auxiliary agent are modified to the methacrylate monomer through side groups; after being complexed with the palladium compound, the nitrogen-phosphorus ligand is coordinated with the palladium compound through the intramolecular synergistic effect of the organic amine auxiliary agent, and a high-molecular catalyst with multiple catalytic active sites is prepared.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of catalyst preparation for coupling reaction, and particularly relates to a temperature-sensitive catalyst for coupling reaction and a preparation method and application thereof. BACKGROUND

[0002] Carbon-carbon bond and carbon heteroatom bond are basic structural units for constructing organic compounds, and transition metal catalyzed coupling method is one of the most effective and direct ways for constructing carbon-carbon bond and carbon heteroatom bond at present. The noble metal catalysts used in such coupling reactions are usually not stable in air and water and are difficult to separate and recover.

[0003] Linear polymer supported noble metal catalyst is one of the methods to solve the above problems. Compared with traditional homogeneous small molecule catalysts, linear polymer catalysts have high reusability, good stability, easy separation from products, and can catalyze organic synthesis reactions under reaction conditions that small molecule catalysts cannot reach. At present, linear polymer catalysts have made certain progress in assisting metal catalyzed coupling reactions. However, the catalytic activity of the catalytic active center at the end of the macromolecular chain is limited by the segmental mobility of the polymer backbone, and the catalytic activity is affected by the polymer matrix, which cannot efficiently catalyze coupling reactions. In addition, the use of excessive organic solvents to precipitate the polymer catalyst is a great waste of chemical resources, which does not meet the requirements of efficient and green transformation strategy. In addition, the traditional polymer catalysts for coupling reactions are usually limited by complex catalyst separation and recovery operations, and are not suitable for intelligent and automated synthesis methods.

[0004] Therefore, how to optimize the catalytic performance and recovery method of the catalyst by using the characteristics of polymer materials is still an important technical bottleneck at present. SUMMARY

[0005] In view of the technical problems in the background art, the present application provides a temperature-sensitive catalyst for coupling reaction and a preparation method and application thereof, aiming to solve the problems of low catalytic activity and difficult separation and recovery of the existing polymer catalysts for coupling reaction.

[0006] In a first aspect, the present application provides a temperature-sensitive catalyst for coupling reaction, and the structure of the temperature-sensitive catalyst is as follows:

[0007] ;

[0008] In the formula, x is an integer between 5 and 30, y is an integer between 0 and 5, and z is an integer between 1 and 10, wherein x:y:z is (5-20):(0-2):(2-5);

[0009] m is an integer between 5 and 25.

[0010] In a second aspect, the embodiments of the present application provide a preparation method of a temperature-sensitive catalyst for a coupling reaction, which comprises the following steps: mixing polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate, a nitrogen-phosphorus monomer and an additive to generate a copolymer, and then complexing the copolymer with a palladium compound to obtain the temperature-sensitive catalyst.

[0011] The nitrogen-phosphorus monomer has the following structural formula:

[0012] .

[0013] In the technical scheme of the embodiments of the present application, Cy in the structural formula of the nitrogen-phosphorus monomer is a cyclohexyl group.

[0014] Preferably, the synthesis of the nitrogen-phosphorus monomer comprises the following steps:

[0015]

[0016] S1, putting o-azidobromobenzene (compound 1), p-ethynylphenol and copper sulfate pentahydrate, sodium ascorbate into a round-bottom flask, adding methanol to completely dissolve them, purging with an inert gas to remove oxygen, heating and stirring to perform a reaction, and obtaining a first product (compound 2) through post-treatment;

[0017] S2, putting the first product, TBSCl and imidazole into a round-bottom flask, then adding dichloromethane to completely dissolve them, purging with an inert gas to remove oxygen, heating and stirring to perform a hydroxyl protection reaction, and obtaining a second product (compound 3) through post-treatment;

[0018] S3, putting the second product into a Schlenk tube, adding tetrahydrofuran to completely dissolve it, purging with an inert gas to remove oxygen, adjusting the temperature to-78 ℃, and then adding n-butyllithium and dicyclohexylphosphine chloride drop by drop, adjusting the temperature to room temperature, and then removing the hydroxyl protection group through tetrabutylammonium fluoride, and obtaining a third product (compound 4) through post-treatment;

[0019] S4, putting the third product and triethylamine into a Schlenk tube, adding dichloromethane to completely dissolve them, purging with an inert gas to remove oxygen, adding methacryloyl chloride drop by drop under ice water bath conditions for 4h, and obtaining the nitrogen-phosphorus monomer NPMA through post-treatment.

[0020] Preferably, the molar ratio of polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate and the nitrogen-phosphorus monomer is (5-20):(0-2):(2-5).

[0021] Preferably, the palladium compound is palladium acetate (PdOAc2) or tris(dibenzylideneacetone)dipalladium (Pd2Dba3), and the molar ratio of palladium atoms in the palladium compound to phosphorus atoms in the copolymer is 1:(1-2).

[0022] Preferably, the method comprises the following steps:

[0023] S1, after mixing polyethylene glycol methyl ether methacrylate, an initiator, a chain transfer agent, and a reaction solvent, introducing an inert gas to remove oxygen, heating and stirring to carry out a polymerization reaction to obtain a first reaction solution;

[0024] S2, adding dimethylaminoethyl methacrylate and nitrogen and phosphorus monomers to the first reaction solution, heating and stirring to carry out polymerization reaction to obtain a second reaction solution, adding the second reaction solution dropwise to the precipitation solvent, filtering and drying to obtain a copolymer;

[0025] S3. Mixing the copolymer, the palladium compound, and toluene to react to obtain a third reaction liquid, adding the third reaction liquid dropwise into a precipitation solvent, filtering, and drying to obtain a temperature-sensitive catalyst.

[0026] In the technical solution of the embodiment of the present application, the structural formulas of the three monomers, polyethylene glycol methyl ether methacrylate (OEGMA), dimethylaminoethyl methacrylate (NMA) and nitrogen phosphorus monomer (NPMA), are as follows:

[0027] , , .

[0028] The reaction formula of step S1 and step S2 is as follows (1):

[0029] ;

[0030] The reaction formula of step S3 is as follows (2):

[0031] .

[0032] Polyethylene glycol methyl ether methacrylate is a temperature-sensitive monomer, which makes the catalyst have temperature-sensitive characteristics. The nitrogen-phosphorus monomer is used to complex the palladium catalyst. Dimethylaminoethyl methacrylate is used as an amine auxiliary to assist the phosphorus ligand in the nitrogen-phosphorus monomer to complex the palladium catalyst.

[0033] Preferably, in step S1, the molar ratio of polyethylene glycol methyl ether methacrylate to the initiator is 10:(1-5), and the initiator is azobisisobutyronitrile (AIBN) or dibenzoyl peroxide.

[0034] Preferably, the molar ratio of polyethylene glycol methyl ether methacrylate to the chain transfer agent is (5-20):1, the chain transfer agent is 2-[[(hexylthio)thiocarbonyl]thio]-propionic acid; and the precipitation solvent includes one or more of cold methyl tert-butyl ether, diethyl ether, and petroleum ether.

[0035] Preferably, the polymerization reaction temperature in step S1 is 60-90° C., and the reaction time is 6-24 h;

[0036] The polymerization temperature in step S2 is 60-90℃, and the reaction time is 6-24h.

[0037] The reaction temperature in step S3 is 20-50℃, and the reaction time is 4-12h.

[0038] Preferably, the molar ratio of palladium atoms in the palladium compound to phosphorus atoms in the copolymer in step S3 is 1:(1-2), the reaction temperature is 20-50℃, and the reaction time is 4-12h.

[0039] In a third aspect, the embodiments of the present application provide an application of the temperature-sensitive catalyst for a coupling reaction, and the coupling reaction catalyzed by the temperature-sensitive catalyst includes any one of a C-C coupling reaction of aryl halide and aryl boronic acid compound, a C-C coupling reaction of aryl halide and monosubstituted olefin, a C-C coupling reaction of aryl halide and monosubstituted alkyne, and a C-N coupling reaction of aryl halide and amine compound.

[0040] The coupling reaction temperature is higher than the lower critical solution temperature of the temperature-sensitive catalyst, and the catalyst can be recovered by cooling to a temperature lower than the lower critical solution temperature of the temperature-sensitive catalyst after the coupling reaction is completed.

[0041] In a fourth aspect, the embodiments of the present application provide a method for flow circulation catalytic coupling reaction, including the following steps:

[0042] The temperature-sensitive catalyst and the basic salt are dispersed in water to form solution A, the coupling reaction raw materials are dispersed in a solvent to form solution B, and solution A and solution B are injected into a microfluidic device respectively to perform flow circulation catalytic coupling reaction.

[0043] The microfluidic device includes a first feeding pump, a second feeding pump, a mixer, a reactor and a separator, the outlet of the first feeding pump is connected to the feeding port of the mixer for conveying solution A, the outlet of the second feeding pump is connected to the feeding port of the mixer for conveying solution B, the outlet of the mixer, the reactor and the separator are sequentially connected, the catalyst reflux pipe and the outlet pipe are arranged in the separator, the catalyst reflux pipe is connected to the feeding port of the first feeding pump through a reflux pump, and the outlet pipe is used for discharging the coupling reaction product.

[0044] The reaction temperature set in the reactor is higher than the lower critical solution temperature of the temperature-sensitive catalyst, and the temperature set in the separator is lower than the lower critical solution temperature of the temperature-sensitive catalyst.

[0045] Compared with the prior art, the beneficial effects of the present application include:

[0046] The application provides a temperature-sensitive polymer catalyst, which is formed by complexing a copolymer POEGMA-b-P(NPMA-co-NMA) of three monomers with a palladium compound. The polyethylene glycol methyl ether methacrylate (POEGMA) unit is mainly used to ensure the temperature sensitivity of the whole catalyst structure; and the small molecule nitrogen phosphorus ligand and the organic amine auxiliary are modified to the methacrylate monomer in the form of side groups, so that the small molecule nitrogen phosphorus ligand and the organic amine auxiliary are loaded on the P(NPMA-co-NMA) segment of the polymer; after being complexed with the palladium compound, the intramolecular synergistic effect of the organic amine auxiliary assists the coordination between the nitrogen phosphorus ligand and the palladium compound, and a polymer catalyst with multiple catalytic active sites is prepared. In related performance tests, it is found that the catalyst can be used to catalyze the coupling reaction of aryl halides. The POEGMA segment as a temperature-sensitive polymer structure has a specific lower critical solution temperature (LCST) in the solution of water and toluene phases, so that the polymer catalyst can return to the water phase by adjusting the temperature after the catalytic reaction is completed, and then the catalyst recycling is realized. The temperature sensitivity is combined with microfluidic technology to realize the flow cycle catalysis of aryl halide coupling reaction.

[0047] The above description is only a summary of the technical solutions of the application, in order to more clearly understand the technical means of the application, the specific embodiments of the application can be implemented according to the content of the description, and in order to make the above and other purposes, characteristics and advantages of the application more obvious and easy to understand, the following specific embodiments of the application are described. BRIEF DESCRIPTION OF DRAWINGS

[0048] In order to more clearly illustrate the technical solutions of the application, the following will briefly introduce the drawings used in the application. Obviously, the drawings described below are only some embodiments of the application, and other drawings can be obtained by those skilled in the art without creating labor.

[0049] Figure 1 It is the nuclear magnetic resonance spectrum of the nitrogen phosphorus monomer NPMA in example 1 of the application.

[0050] Figure 2 It is the structure formula of the temperature-sensitive catalyst in example 2 of the application.

[0051] Figure 3 It is the optical picture of the temperature-sensitive catalyst in example 2 of the application shuttling back and forth between water phase and toluene phase in response to temperature; 3a is the position of the temperature-sensitive catalyst at room temperature; 3b is the position of the temperature-sensitive catalyst when heated to 70 DEG C; 3c is the position of the temperature-sensitive catalyst after cooling.

[0052] Figure 4 It is a schematic diagram of a microfluidic device in example 12 of the application.

[0053] Reference Signs List:

[0054] 1, first feed pump; 2, second feed pump; 3, mixer; 4, reactor; 5, separator; 6, reflux pump. DETAILED DESCRIPTION

[0055] The embodiments of the present application will be described in detail below with reference to the drawings. The following examples are only used to more clearly illustrate the technical scheme of the present application, and therefore only serve as examples, but cannot be used to limit the protection scope of the present application.

[0056] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs; the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application; the description and the drawings are to be regarded as illustrative in nature; the terms "comprising," "comprises" and "including," "includes" as used herein, are meant to be interpreted in an inclusive manner and indicate the presence of stated features but not to the exclusion of additional possible features.

[0057] In the description of the embodiments of the present application, the technical terms "first", "second", etc. are only used to distinguish different objects, and cannot be understood as indicating or implying relative importance or implicitly indicating the number, specific order or primary and secondary relationship of the indicated technical features. In the description of the embodiments of the present application, the meaning of "a plurality of" is two or more, unless otherwise explicitly and specifically limited.

[0058] Reference in the specification to "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment can be included in at least one embodiment of the application. The appearances of the phrase in various places in the specification are not necessarily all referring to the same embodiment, nor are they necessarily mutually exclusive or alternative embodiments. It is expressly understood that the described embodiments are merely examples from a whole class of comparable embodiments which those skilled in the art will readily appreciate. It is also specifically intended that individual features or aspects from any embodiment can be provided independently of any other embodiments, regardless of whether the feature or aspect is claimed in that embodiment or not.

[0059] In the description of the embodiments of the present application, the term "and / or" is only a description of the association relationship of the associated objects, which means that there can be three relationships, for example, A and / or B, which can represent the three cases of A alone, A and B together, and B alone. In addition, the character " / " in this paper generally represents that the front and rear associated objects are a "or" relationship.

[0060] In the description of the embodiments of the present application, the term "a plurality of" refers to two or more (including two), and similarly, "a plurality of groups" refers to two or more groups (including two groups), and "a plurality of pieces" refers to two or more pieces (including two pieces).

[0061] Carbon-carbon bond and carbon heteroatom bond are the basic structural units of organic compounds, and transition metal catalyzed coupling method is one of the most effective and direct ways to construct carbon-carbon bond and carbon heteroatom bond. The noble metal catalysts used in such coupling reactions are usually not stable in air and water and are difficult to separate and recover. Linear polymer loading of noble metal catalyst is one of the methods to solve the above problems, but how to use the characteristics of high polymer materials to optimize the catalytic performance and recovery method of the catalyst is still an important technical bottleneck at present.

[0062] In order to solve the problem that the noble metal catalyst in the prior art is not stable in air and water and is difficult to separate and recover, the present application provides a temperature-sensitive catalyst for coupling reaction and its preparation method and application, wherein the small molecule nitrogen phosphorus ligand and the organic amine auxiliary side group are modified to the methyl acrylate monomer, so that the small molecule nitrogen phosphorus ligand and the organic amine auxiliary are loaded on the P(NPMA-co-NMA) segment of the polymer, and after being complexed with the palladium compound, through the intramolecular synergistic effect of the organic amine auxiliary and the multi-catalytic active site of the coordination of the nitrogen phosphorus ligand and the palladium compound, it is found in related performance test that the catalyst can be used to catalyze the coupling reaction of aryl halide. The POEGMA segment as a temperature-sensitive polymer structure has a specific lower critical solution temperature (LCST) in the solution of water and toluene phase, so that the polymer catalyst can be returned to the water phase by adjusting the temperature after the catalytic reaction is completed, and then the catalyst recycling is realized. And the temperature sensitivity is combined with microfluidic technology to realize the flow cycle catalysis of aryl halide coupling reaction.

[0063] In view of the technical problems in the background art, the present application provides a temperature-sensitive catalyst for coupling reaction and its preparation method and application, which aims to solve the problem that the noble metal catalyst in the prior art is not stable in air and water and is difficult to separate and recover.

[0064] In the first aspect, the embodiments of the present application provide a temperature-sensitive catalyst for coupling reaction, and the structure general formula of the temperature-sensitive catalyst is as follows:

[0065] ;

[0066] In the formula, x is an integer between 5 and 30, y is an integer between 0 and 5, and z is an integer between 1 and 10, wherein x:y:z is (5-20):(0-2):(2-5);

[0067] m is an integer between 5 and 25.

[0068] When the proportion of x is too large, the polymer chain is too long, which can wrap the palladium catalyst, thereby causing the catalytic effect to decrease. When the proportion of x is too small, the molecular weight of the temperature-sensitive polymer segment (POEGMA) is too small, and the temperature-sensitive effect of the polymer decreases, which does not have the temperature-sensitive effect of entering the organic phase at high temperature and entering the aqueous phase at low temperature.

[0069] In a second aspect, the embodiment of the present application provides a preparation method of a temperature-sensitive catalyst for a coupling reaction, and the specific steps include: mixing and reacting polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate, a nitrogen-phosphorus monomer and an auxiliary agent to generate a copolymer, and then complexing the copolymer with a palladium compound to obtain the temperature-sensitive catalyst.

[0070] The structure of the nitrogen-phosphorus monomer is as follows:

[0071] .

[0072] ;

[0073] The synthesis of the nitrogen-phosphorus monomer includes the following steps:

[0074] S1, o-azidobromobenzene (compound 1) and p-ethynylphenol, copper sulfate pentahydrate and sodium ascorbate are put into a round-bottom flask, methanol is added to completely dissolve them, inert gas is introduced to remove oxygen, and heating and stirring are performed to carry out the reaction, and the first product (compound 2) is obtained through post-treatment;

[0075] S2, the first product, TBSCl and imidazole are put into a round-bottom flask, and then dichloromethane is added to completely dissolve them, inert gas is introduced to remove oxygen, and heating and stirring are performed to carry out the hydroxyl protection reaction, and the second product (compound 3) is obtained through post-treatment;

[0076] S3, the second product is put into a Schlenk tube, tetrahydrofuran is added to completely dissolve it, inert gas is introduced to remove oxygen, the temperature is adjusted to-78 ℃, n-butyllithium and dicyclohexylphosphine chloride are added dropwise in sequence, the temperature is adjusted to room temperature, and then the reaction is carried out. Then, tetrabutylammonium fluoride is used to remove the hydroxyl protection group, and the third product (compound 4) is obtained through post-treatment;

[0077] S4, the third product and triethylamine are put into a Schlenk tube, dichloromethane is added to completely dissolve them, inert gas is introduced to remove oxygen, and methyl acryloyl chloride is added dropwise under ice water bath conditions for 4h, and then the nitrogen-phosphorus monomer NPMA is obtained through post-treatment.

[0078] In the technical solution of the embodiment of the present application, Cy in the structure formula of the nitrogen-phosphorus monomer is a cyclohexyl group.

[0079] Preferably, the molar ratio of polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate and nitrogen phosphorus monomer is (5-20):(0-2):(2-5).

[0080] Preferably, the palladium compound is palladium acetate (PdOAc2) or tris-dibenzylideneacetone palladium (Pd2Dba3), and the molar ratio of palladium atoms in the palladium compound to phosphorus atoms in the copolymer is 1:(1-2).

[0081] Preferably, the method comprises the following steps:

[0082] S1, mixing polyethylene glycol methyl ether methacrylate, initiator, chain transfer agent and reaction solvent, purging inert gas to remove oxygen, heating and stirring to carry out polymerization reaction to obtain a first reaction liquid;

[0083] S2, adding dimethylaminoethyl methacrylate and nitrogen phosphorus monomer to the first reaction liquid, heating and stirring to carry out polymerization reaction to obtain a second reaction liquid, dropping the second reaction liquid into a precipitating solvent, and then filtering and drying to obtain a copolymer;

[0084] S3, mixing the copolymer, palladium compound and toluene to obtain a third reaction liquid, dropping the third reaction liquid into a precipitating solvent, and then filtering and drying to obtain a temperature-sensitive catalyst.

[0085] In the technical scheme of the embodiment, the structural formulae of polyethylene glycol methyl ether methacrylate (OEGMA), dimethylaminoethyl methacrylate (NMA) and nitrogen phosphorus monomer (NPMA) are as follows:

[0086]

[0087] The reaction formulae of steps S1 and S2 are as follows:

[0088]

[0089] The reaction formula of step S3 is as follows:

[0090]

[0091] Polyethylene glycol methyl ether methacrylate is a temperature-sensitive monomer, which makes the catalyst have temperature-sensitive characteristics, nitrogen phosphorus monomer is used to complex the palladium catalyst, and dimethylaminoethyl methacrylate is used as an amine assistant to assist the complexation of the phosphorus ligand in the nitrogen phosphorus monomer and the palladium catalyst.

[0092] Preferably, the molar ratio of polyethylene glycol methyl ether methacrylate to initiator in step S1 is 10:(1-5), and the initiator is azobisisobutyronitrile (AIBN) or dibenzoyl peroxide. ​​​​​

[0093] Preferably, the molar ratio of polyethylene glycol methyl ether methacrylate to chain transfer agent is (5-20):1, and the chain transfer agent is 2-[[ (hexylthio)thiocarbonyl]thio]-propionic acid; the precipitation solvent includes one or more of cold methyl tert-butyl ether, diethyl ether, petroleum ether.

[0094] Preferably, the polymerization temperature in step S1 is 60-90℃, and the reaction time is 6-24h;

[0095] The polymerization temperature in step S2 is 60-90℃, and the reaction time is 6-24h;

[0096] The reaction temperature in step S3 is 20-50℃, and the reaction time is 4-12h.

[0097] Preferably, the molar ratio of palladium atoms in the palladium compound to phosphorus atoms in the copolymer in step S3 is 1:(1-2), the reaction temperature is 20-50℃, and the reaction time is 4-12h.

[0098] In a third aspect, the embodiments of the present application provide an application of a temperature-sensitive catalyst for a coupling reaction, and the coupling reaction catalyzed by the temperature-sensitive catalyst includes any one of a C-C coupling reaction of an aryl halide with an aryl boronic acid compound, a C-C coupling reaction of an aryl halide with a monosubstituted olefin, a C-C coupling reaction of an aryl halide with a monosubstituted alkyne, and a C-N coupling reaction of an aryl halide with an amine compound.

[0099] The coupling reaction temperature is higher than the lower critical solution temperature of the temperature-sensitive catalyst, and the catalyst can be recovered by cooling to below the lower critical solution temperature of the temperature-sensitive catalyst after the coupling reaction is completed.

[0100] In a fourth aspect, the embodiments of the present application provide a method for flow-circulation catalytic coupling reaction, including the following steps:

[0101] The temperature-sensitive catalyst and the basic salt are dispersed in water to form solution A, the coupling reaction raw materials are dispersed in a solvent to form solution B, and solution A and solution B are injected into a microfluidic device respectively to perform flow-circulation catalytic coupling reaction.

[0102] The microfluidic device includes a first feeding pump, a second feeding pump, a mixer, a reactor, and a separator, the outlet of the first feeding pump is connected to the feeding port of the mixer for conveying solution A, the outlet of the second feeding pump is connected to the feeding port of the mixer for conveying solution B, the outlet of the mixer, the reactor, and the separator are sequentially connected, the catalyst reflux pipe and the outlet pipe are arranged in the separator, the catalyst reflux pipe is connected to the feeding port of the first feeding pump through a reflux pump, and the outlet pipe is used for discharging the coupling reaction product.

[0103] The reaction temperature set in the reactor is higher than the lower critical solution temperature of the temperature-sensitive catalyst, and the temperature set in the separator is lower than the lower critical solution temperature of the temperature-sensitive catalyst.

[0104] Some specific examples are listed below. It should be noted that the examples described below are exemplary and are only used to explain the present application and cannot be understood as a limitation of the present application. If the specific technology or condition is not specified in the examples, the technology or condition described in the literature in the art or according to the product manual is used. If the reagent or instrument is not specified by the manufacturer, it is a conventional product that can be obtained by purchase.

[0105] I. Preparation method

[0106] Example 1

[0107] A preparation method for synthesizing a temperature-sensitive catalyst monomer NPMA

[0108] The o-bromo-azide benzene (1.1782 g) and p-ethynylphenol (1.2762 g) and copper sulfate pentahydrate (0.045 g) and sodium ascorbate (0.4458 g) were weighed into a 100 mL round-bottom flask, then 12 mL of methanol was added to completely dissolve them, and then 6 mL of water was added. The reaction was carried out at 40°C for 8 h under a nitrogen atmosphere. After the reaction was completed, 25 mL of ethyl acetate was added, and each was washed with 20 mL of water and saturated brine three times. Anhydrous sodium sulfate was dried, the organic phase was evaporated and concentrated, and then 1.03 g of the first product (compound 1) was obtained by silica gel column purification (yield 55%).

[0109] The first product (compound 2) (0.6 g) and TBSCl (0.3718 g) and imidazole (0.1680 g) were weighed into a 100 mL round-bottom flask, then 12 mL of dichloromethane was added to completely dissolve them, and the reaction was carried out at 30°C for 4 h under a nitrogen atmosphere. After the reaction was completed, 25 mL of dichloromethane was added, and each was washed with 20 mL of water and saturated brine three times. Anhydrous sodium sulfate was dried, the organic phase was evaporated and concentrated, and then 0.76 g of the second product (compound 3) was obtained by silica gel column purification (yield 96%).

[0110] The second product (compound 3) (0.4 g) was weighed into a 25 mL Schlenk tube, 4 mL of tetrahydrofuran was added to completely dissolve it, the temperature was adjusted to -78 ℃ under nitrogen atmosphere, 2.5 mol / L n-butyllithium (0.5019 mL) was added dropwise, and after 30 min, dicyclohexylphosphine chloride (0.6736 g) was added dropwise, and the reaction was carried out at room temperature for 8 h. Then the reaction temperature was adjusted to room temperature, 1 mol / L tetrabutylammonium fluoride (1.4478 mL) was added, and the reaction was carried out for 4 h. After the reaction was completed, 25 mL of ethyl acetate was added, and each was washed with 20 mL of water and saturated brine three times, dried over anhydrous sodium sulfate, and the organic phase was evaporated and concentrated, and then purified by silica gel column to obtain 0.42 g of the third product (compound 4) (yield 59%).

[0111] The third product (compound 4) (0.34 g) and triethylamine (0.1588 g) were weighed into a 25 mL Schlenk tube, then 5 mL of dichloromethane was added to completely dissolve it, and methyl acryloyl chloride (0.1639 g) was added dropwise under ice water bath conditions, and the reaction was carried out for 4 h. After the reaction was completed, 25 mL of dichloromethane was added, and each was washed with 20 mL of water and saturated brine three times, dried over anhydrous sodium sulfate, and the organic phase was evaporated and concentrated, and then purified by silica gel column to obtain 0.36 g of the product nitrogen phosphorus monomer NPMA (yield 91%), and the nuclear magnetic resonance hydrogen spectrum is as shown in Figure 1

[0112] Example 2

[0113] A preparation method of a temperature-sensitive catalyst for a coupling reaction:

[0114] OEGMA 950 (950 mg) and azobisisobutyronitrile AIBN (16 mg) and 2-[[ (hexylthio) thioformyl] thio] -propionic acid (27 mg) were weighed into a 25 mL Schlenk tube, then 2 mL of dimethyl sulfoxide (DMSO) was added to completely dissolve it, and the reaction was carried out at 70 ℃ under nitrogen atmosphere for 24 h. Then NMA (31 mg) and the nitrogen phosphorus monomer NPMA (245 mg) prepared in Example 1 were dissolved in 1 mL of DMSO and added, and the reaction was carried out at 70 ℃ under nitrogen atmosphere for 24 h. After the reaction was completed, the reaction solution was dropped into 100 mL of precipitating solvent cold methyl tert-butyl ether, and a solid was precipitated, and POEGMA 950 - b- P(NPMA- co- ​NMA) (x:y:z = 10:2:5 light yellow filter cake). Copolymer 175 mg and palladium acetate 16 mg were added to the reaction vessel with 2 mL of toluene under a nitrogen atmosphere, and stirred at 50 °C for 2 h to obtain a temperature-sensitive catalyst, the structure of which is as follows Figure 2 as shown.

[0115] Example 3

[0116] A method for preparing a temperature-sensitive catalyst for a coupling reaction:

[0117] OEGMA 950 (950 mg) and AIBN (32 mg) and 2-[[ (hexylthio)thiocarbonyl]thio]-propionic acid (27 mg) were placed in a 25 mL Schlenk tube, then 2 mL of dimethylacetamide (DMF) was added to completely dissolve it, and the reaction was heated at 80 °C for 12 h under a nitrogen atmosphere. Then NMA (16 mg) and the nitrogen-phosphorus monomer NPMA (245 mg) prepared in Example 1 were dissolved in 1 mL of DMF and added, and the reaction was heated at 70 °C for 12 h under a nitrogen atmosphere. After the reaction was completed, the reaction solution was dropped into 100 mL of cold ether, and a solid was precipitated, which was filtered to obtain POEGMA 950 - b- P(NPMA- co- NMA) (x:y:z = 10:1:5 light yellow filter cake). Copolymer 169 mg and Pd2(Dba)3 16 mg were added to the reaction vessel with 2 mL of toluene under a nitrogen atmosphere, and stirred at 40 °C for 4 h to obtain a temperature-sensitive catalyst.

[0118] Example 4

[0119] A method for preparing a temperature-sensitive catalyst for a coupling reaction:

[0120] OEGMA 950 (475 mg) and AIBN (32 mg) and 2-[[ (hexylthio)thiocarbonyl]thio]-propionic acid (27 mg) were placed in a 25 mL Schlenk tube, then 2 mL of DMSO was added to completely dissolve it, and the reaction was heated at 60 °C for 24 h under a nitrogen atmosphere. Then NMA (16 mg) and the nitrogen-phosphorus monomer NPMA (245 mg) prepared in Example 1 were dissolved in 1 mL of DMSO and added, and the reaction was heated at 60 °C for 24 h under a nitrogen atmosphere. After the reaction was completed, the reaction solution was dropped into 100 mL of cold methyl tert-butyl ether, and a solid was precipitated, which was filtered to obtain POEGMA 950 - b- P(NPMA- co-Under nitrogen atmosphere, 102 mg of the copolymer and 16 mg of Pd2(Dba)3 were added to a reaction vessel along with 2 mL of toluene. The mixture was stirred at 30°C for 6 h to obtain a thermosensitive catalyst.

[0121] Example 5

[0122] A method for preparing a temperature-sensitive catalyst for coupling reaction:

[0123] Weigh OEGMA 950 (475 mg) and AIBN (16 mg) and 2-[[(hexylthio)thiocarbonyl]thio]-propionic acid (27 mg) were placed in a 25 mL Schlenk tube, and then 2 mL of DMF was added to completely dissolve them. The mixture was heated at 90°C under a nitrogen atmosphere for 8 h. NMA (32 mg) and the nitrogen-phosphorus monomer NPMA (98 mg) prepared in Example 1 were then weighed, dissolved in 1 mL of DMF, and added. The mixture was heated at 60°C under a nitrogen atmosphere for 8 h. After the reaction was complete, the reaction solution was added dropwise to 100 mL of cold ether. Solid precipitated and was filtered to obtain POEGMA. 950 - b- P(NPMA- co- NMA) (x:y:z = 5:2:2 pale yellow filter cake). Under a nitrogen atmosphere, 215 mg of the copolymer and 8 mg of palladium acetate were added to 2 mL of toluene in a reaction vessel and stirred at 40°C for 4 h to obtain a temperature-sensitive catalyst.

[0124] Example 6

[0125] Weigh OEGMA 950 (950 mg) and dibenzoyl peroxide (24 mg) along with 2-[[(hexylthio)carbonylthio]thio]-propionic acid (27 mg) were placed in a 25 mL Schlenk tube. 2 mL of dimethyl sulfoxide (DMSO) was then added to completely dissolve the mixture. The mixture was heated at 70°C under a nitrogen atmosphere for 24 h. NPMA (245 mg) was then weighed and dissolved in 1 mL of DMSO. The mixture was then heated at 70°C under a nitrogen atmosphere for 24 h. After the reaction was complete, the reaction solution was added dropwise to 100 mL of cold petroleum ether, a precipitation solvent. A solid precipitated, which was filtered to obtain POEGMA. 950 - b- P(NPMA) (x:y:z = 10:0:5 pale yellow filter cake). Under a nitrogen atmosphere, 175 mg of the copolymer and 16 mg of palladium acetate were added to a reaction vessel along with 2 mL of toluene. The mixture was stirred at 50°C for 2 h to obtain a thermosensitive catalyst.

[0126] Example 7

[0127] To 0.4 mg of catalyst prepared in Example 2, 244 mg of cesium carbonate and 125 mg of p-methoxyphenylboronic acid, 118 mg of bromobenzene were dissolved in 0.2 mL of toluene and 0.8 mL of water and reacted at 70 °C for 2 h. After the reaction was completed, the temperature was lowered to room temperature and the reaction product was in the organic phase and the catalyst was in the lower aqueous phase. The upper organic phase was removed and the aqueous phase containing the catalyst was used directly for the second reaction, and additionally 244 mg of cesium carbonate, 125 mg of p-methoxyphenylboronic acid, 118 mg of bromobenzene and 0.2 mL of toluene were added and reacted at 80 °C for 2 h, and the reaction was repeated twice. The coupling reaction equation of p-methoxyphenylboronic acid and bromobenzene is as follows:

[0128] .

[0129] Example 8

[0130] To 0.4 mg of catalyst prepared in Example 2, 244 mg of cesium carbonate and 86 mg of styrene, 118 mg of bromobenzene were dissolved in 0.2 mL of toluene and 0.8 mL of water and reacted at 70 °C for 5 h.

[0131] The coupling reaction equation of styrene and bromobenzene is as follows:

[0132] .

[0133] Example 9

[0134] To 0.4 mg of catalyst prepared in Example 2, 104 mg of potassium carbonate and 84 mg of phenylacetylene, 118 mg of bromobenzene were dissolved in 0.2 mL of toluene and 0.8 mL of water and reacted at 70 °C for 5 h.

[0135] The coupling reaction equation of phenylacetylene and bromobenzene is as follows:

[0136] .

[0137] Example 10

[0138] To 0.4 mg of catalyst prepared in Example 2, 104 mg of potassium carbonate and 96 mg of phenylamine, 118 mg of bromobenzene were dissolved in 0.2 mL of toluene and 0.8 mL of water and reacted at 70 °C for 8 h, and the conversion rate was detected using gas chromatography.

[0139] The coupling reaction equation of phenylamine and bromobenzene is as follows:

[0140] .

[0141] Example 11

[0142] 0.4 mg of the catalyst prepared in Example 6, 244 mg of cesium carbonate, 125 mg of p-methoxyphenylboronic acid, and 118 mg of bromobenzene were dissolved in 0.2 mL of toluene and 0.8 mL of water and reacted at 70°C for 2 h. The coupling reaction equation of p-methoxyphenylboronic acid and bromobenzene is as follows:

[0143] .

[0144] Example 12

[0145] Microfluidic devices are used to realize flow cycle catalytic coupling reactions, such as co- As shown, the microfluidic device includes a first feed pump 1, a second feed pump 2, a mixer 3, a reactor 4 and a separator 5. The first feed pump 1 and the second feed pump 2 are used to transport solution A and solution B respectively. The discharge ports of the first feed pump 1 and the second feed pump 2 are connected to the feed port of the mixer 3. The discharge port of the mixer 3, the reactor 4 and the separator 5 are connected in sequence. The reaction temperature set in the reactor 4 is higher than the lower critical solution temperature of the temperature-sensitive catalyst, and the temperature set in the separator 4 is lower than the lower critical solution temperature of the temperature-sensitive catalyst. The separator 4 is provided with a catalyst reflux pipe and a discharge pipe. The catalyst reflux pipe is connected to the feed port of the first feed pump 1 through a reflux pump 6. After the reaction of solution A and solution B in the reactor is completed, they flow into the separator 4. The temperature in the separator 4 is relatively low, and the temperature-sensitive catalyst returns from the toluene phase to the aqueous phase and is recycled through the reflux pipe set in the aqueous phase. The organic phase and product without catalyst are discharged along the discharge pipe.

[0146] 5 mg of the catalyst prepared in Example 2 and 1.38 g of potassium carbonate were dissolved in 4 mL of water to form solution A. 3.35 g of phenylboric acid and 3.14 g of bromobenzene were dissolved in 8 mL of toluene to form solution B. Figure 4 As shown, solutions A and B were transferred to syringes and attached to first feed pump 1 and second feed pump 2. The entire flow path was pre-rinsed with toluene. Solutions A and B were then continuously fed into reactor 4 via first feed pump 1 and second feed pump 2. Reactor 4 was maintained at 70°C. The catalyst was transferred to the toluene phase containing the coupling reaction raw materials for catalytic reaction. The flow rates of solutions A and B were controlled at 40 µL / min and 10 µL / min, respectively. The temperature in separator 4 was maintained at room temperature. After 3 hours of reaction, all organic phases were separated, and the aqueous phase was extracted with ethyl acetate. The organic phases were collected, dried, and concentrated to remove the solvent. The resulting crude product was purified by column chromatography to yield the desired product.

[0147] Comparative Example 1

[0148] Take 0.4 mg of ordinary coupling reaction catalyst (triphenylphosphine) palladium, 244 mg of cesium carbonate and 125 mg of p-methoxyphenylboronic acid, 118 mg of bromobenzene dissolved in 0.5 mL of toluene, and react at 70°C for 2 h.

[0149] Comparative Example 2

[0150] Take OEGMA 950 (950 mg) and azobisisobutyronitrile AIBN (16 mg) and 2-[[ (hexylthio) thioformyl] thio] -propionic acid (27 mg) into a 25 mL Schlenk tube, then add 2 mL of dimethyl sulfoxide (DMSO) to completely dissolve it, and heat it at 70°C for 24 h under a nitrogen atmosphere. Then take NMA (31 mg) and dissolve it in 1 mL of DMSO, and then add it, and heat it at 70°C for 24 h under a nitrogen atmosphere. After the reaction is complete, the reaction solution is dropped into 100 mL of cold methyl tert-butyl ether as the precipitating solvent, and solid is precipitated, and POEGMA 950 - b- P(NMA) (x:y:z = 10:2:0 light yellow filter cake). Because the polymer lacks a phosphorus ligand to complex palladium acetate, it cannot form a temperature-sensitive catalyst.

[0151] Comparative Example 3

[0152] Take OEGMA 950 (950 mg) and azobisisobutyronitrile AIBN (16 mg) and 2-[[ (hexylthio) thioformyl] thio] -propionic acid (27 mg) into a 25 mL Schlenk tube, then add 2 mL of dimethyl sulfoxide (DMSO) to completely dissolve it, and heat it at 70°C for 24 h under a nitrogen atmosphere. Then take NMA (155 mg) and NPMA (245 mg) and dissolve them in 1 mL of DMSO, and then add them, and heat them at 70°C for 24 h under a nitrogen atmosphere. After the reaction is complete, the reaction solution is dropped into 100 mL of cold methyl tert-butyl ether as the precipitating solvent, and solid is precipitated, and POEGMA 950 - b- P(NPMA- Figure 4 NMA) (x:y:z = 10:10:5 light yellow filter cake). After temperature-sensitive testing, the polymer lost its temperature sensitivity because the x:y ratio was too large at 1:1.

[0153] Comparative Example 4

[0154] Take OEGMA 950(950 mg) and azobisisobutyronitrile AIBN (16 mg) and 2-[[ (hexylthio)thiocarbonyl]thio]-propionic acid (27 mg) were placed into a 25 mL Schlenk tube, then 2 mL dimethyl sulfoxide (DMSO) was added to completely dissolve them, and the reaction was heated at 70 °C for 24 h under a nitrogen atmosphere. Then NMA (31 mg) and NPMA (490 mg) were weighed and dissolved in 1 mL DMSO and added, and the reaction was heated at 70 °C for 24 h under a nitrogen atmosphere. After the reaction was completed, the reaction solution was dropped into 100 mL of a precipitating solvent, cold methyl tert-butyl ether, and a solid was precipitated, and POEGMA was obtained by filtration 950 - b- P(NPMA- co- NMA) (x:y:z = 10:2:10 light yellow filter cake). After the temperature sensitivity test, the temperature sensitivity of the polymer disappeared because the x:z ratio was too large, 1:1.

[0155] Comparative Example 5

[0156] OEGMA 950 (1900 mg) and azobisisobutyronitrile AIBN (32 mg) and 2-[[ (hexylthio)thiocarbonyl]thio]-propionic acid (27 mg) were placed into a 25 mL Schlenk tube, then 2 mL dimethyl sulfoxide (DMSO) was added to completely dissolve them, and the reaction was heated at 70 °C for 24 h under a nitrogen atmosphere. Then NMA (16 mg) and NPMA (98 mg) were weighed and dissolved in 1 mL DMSO and added, and the reaction was heated at 70 °C for 24 h under a nitrogen atmosphere. After the reaction was completed, the reaction solution was dropped into 100 mL of a precipitating solvent, cold methyl tert-butyl ether, and a solid was precipitated, and POEGMA was obtained by filtration 950 - b- P(NPMA- co- NMA) (x:y:z = 20:1:2 light yellow filter cake). Under a nitrogen atmosphere, 800 mg of the copolymer and 16 mg of palladium acetate were added to a reaction vessel along with 2 mL of toluene, and the mixture was stirred at 50 °C for 2 h to obtain a temperature-sensitive catalyst.

[0157] Comparative Example 6

[0158] 0.4 mg of the catalyst prepared in Comparative Example 5, 244 mg of cesium carbonate, and 125 mg of p-methoxyphenylboronic acid were dissolved in 0.2 mL of toluene and 0.8 mL of water, and the mixture was reacted at 70 °C for 2 h. The coupling reaction equation of p-methoxyphenylboronic acid and bromobenzene is as follows:

[0159] .

[0160] II. Analysis of test results of each example and comparative example

[0161] (1) Water and toluene were poured into a test tube in turn, and the temperature-sensitive catalyst prepared in Example 2 was added into the test tube, and the change of the catalyst at different temperatures was observed. It can be seen from co- a that the catalyst was in the water phase at room temperature; after the test tube was heated to 70°C, the catalyst was seen to Figure 3 b, transfer from the water phase to the toluene phase and dissolve in the toluene phase; after the test tube was cooled to room temperature, the catalyst was seen to Figure 3 Figure 3 c, return from the toluene phase to the water phase. It can be seen that the catalyst obtained in Example 2 can shuttle between the water and toluene phases by adjusting the temperature, which is convenient for recycling the catalyst.

[0162] (2) The conversion rates of the coupling reaction in Example 7 for the first time and the coupling reactions in Examples 8-11 and Comparative Examples 1 and 6 were detected by gas chromatography, and the detection results are shown in Table 1 below.

[0163] Table 1: Coupling reaction conversion rate detection data of various examples and comparative examples

[0164]

[0165] It can be seen from Table 1 that the temperature-sensitive catalyst prepared in Example 2 catalyzes various coupling reactions, and a conversion rate of more than 90% can be obtained; the temperature-sensitive catalyst prepared in Example 6 is used in Example 11, and the catalytic activity is low in the coupling reaction; it is indicated that the nitrogen-phosphorus monomer is used to complex the palladium catalyst, and the dimethylaminoethyl methacrylate is used as an amine assistant to assist the phosphorus ligand in the nitrogen-phosphorus monomer to complex the palladium catalyst, and the catalyst prepared by the synergistic effect of the two can obtain good catalytic effect.

[0166] The yield of the ordinary catalyst in Comparative Example 1 is only 86%, and the palladium in the catalyst cannot be recycled, and the cost is high.

[0167] In Comparative Example 2, the nitrogen-phosphorus monomer is not used, and the temperature-sensitive catalyst cannot be synthesized; in Comparative Example 3, the y:x ratio is too large, and the amount of dimethylaminoethyl methacrylate added is too high; in Comparative Example 4, the z:x ratio is too large, and the amount of nitrogen-phosphorus monomer added is too high; the temperature sensitivity of the catalyst in Comparative Examples 3 and 4 disappears, which indicates that when the x ratio is too small, the molecular weight of the temperature-sensitive polymer segment (POEGMA) is too small, and the temperature sensitivity effect of the polymer decreases, and the temperature sensitivity effect of entering the organic phase at high temperature and entering the water phase at low temperature is not possessed.

[0168] In Comparative Example 6, the catalyst prepared in Comparative Example 5 is used, and the conversion rate of the coupling reaction is greatly reduced, which indicates that when the x ratio is too large, the polymer chain is too long, which can wrap the palladium catalyst and cause the catalytic effect to decrease.

[0169] (3) The conversion rates of the first coupling reaction and the two coupling reactions after the catalyst recycling in Example 7 were detected by gas chromatography. The detection results are shown in Table 2 below.

[0170] Table 2 Coupling reaction conversion rate test data after catalyst recycling

[0171]

[0172] It can be seen from Table 2 that the catalyst can still maintain a high coupling reaction conversion rate after being recycled multiple times.

[0173] It should be noted that the present application is not limited to the above-mentioned embodiments. The above-mentioned embodiments are merely examples, and any embodiments having substantially the same structure and effect as the technical concept within the scope of the present application are all included in the technical scope of the present application. In addition, without departing from the scope of the present application, any other embodiments that can be conceived by those skilled in the art and that combine some of the constituent elements in the embodiments are also included in the scope of the present application.

Claims

1. A temperature-sensitive catalyst for coupling reaction, characterized in that: The general structural formula of the temperature-sensitive catalyst is as follows: ； Wherein x is an integer between 5 and 30, y is an integer between 0 and 5, and z is an integer between 1 and 10, wherein x:y:z is one of 10:2:5, 10:1:5, 5:1:5, 5:2:2 or 10:0:5; m is an integer between 5 and 25.

2. A method for preparing a temperature-sensitive catalyst for a coupling reaction, characterized in that: The preparation method is used to prepare the temperature-sensitive catalyst according to claim 1, and the specific steps include: mixing polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate, nitrogen and phosphorus monomers and additives to form a copolymer, and then complexing with a palladium compound to obtain the temperature-sensitive catalyst; The structural formula of the nitrogen-phosphorus monomer is as follows: 。 3. The method for preparing a temperature-sensitive catalyst for a coupling reaction according to claim 2, wherein The synthesis of the nitrogen-phosphorus monomer comprises the following steps: S1. Completely dissolving o-bromobenzene azide, p-acetylene phenol, copper sulfate pentahydrate, and sodium ascorbate in methanol, introducing an inert gas to remove oxygen, heating and stirring to react, and obtaining a first product through post-treatment; S2, dissolving the first product, TBSCl, and imidazole completely in dichloromethane, introducing an inert gas for deoxygenation, heating and stirring to perform a hydroxyl protection reaction, and obtaining a second product by post-treatment; S3, the second product is completely dissolved in tetrahydrofuran, an inert gas is introduced to remove oxygen, the temperature is adjusted to -78 ° C, n-butyl lithium and dicyclohexylphosphine chloride are added dropwise successively, the temperature is adjusted to room temperature for reaction, and the hydroxyl protecting group is then removed by tetrabutylammonium fluoride, and the third product is obtained by post-treatment; S4. The third product and triethylamine are completely dissolved in dichloromethane, an inert gas is introduced to remove oxygen, methacryloyl chloride is added dropwise in an ice-water bath, and the mixture is reacted for 4 hours. The nitrogen-phosphorus monomer is obtained through post-treatment.

4. The method for preparing a temperature-sensitive catalyst for a coupling reaction according to claim 2, wherein The palladium compound is Pd(OAc)2 or Pd2(Dba)3, and the molar ratio of palladium atoms in the palladium compound to phosphorus atoms in the copolymer is 1:(1-2).

5. The method for preparing a temperature-sensitive catalyst for a coupling reaction according to any one of claims 2 to 4, wherein: The steps include: S1, after mixing polyethylene glycol methyl ether methacrylate, an initiator, a chain transfer agent, and a reaction solvent, introducing an inert gas to remove oxygen, heating and stirring to carry out a polymerization reaction to obtain a first reaction solution; S2, adding dimethylaminoethyl methacrylate and nitrogen and phosphorus monomers to the first reaction solution, heating and stirring to carry out polymerization reaction to obtain a second reaction solution, adding the second reaction solution dropwise to the precipitation solvent, filtering and drying to obtain a copolymer; S3. Mixing the copolymer, the palladium compound, and toluene to react to obtain a third reaction liquid, adding the third reaction liquid dropwise into a precipitation solvent, filtering, and drying to obtain a temperature-sensitive catalyst.

6. The method for preparing a temperature-sensitive catalyst for coupling reaction according to claim 5, wherein In step S1, the molar ratio of polyethylene glycol methyl ether methacrylate to the initiator is 10:(1-5), and the initiator is azobisisobutyronitrile or dibenzoyl peroxide.

7. The method for preparing a temperature-sensitive catalyst for coupling reaction according to claim 5, wherein The molar ratio of the polyethylene glycol methyl ether methacrylate to the chain transfer agent is (5-20):1, and the chain transfer agent is 2-[[(hexylthio)thiocarbonyl]thio]-propionic acid; and the precipitation solvent includes one or more of cold methyl tert-butyl ether, diethyl ether, and petroleum ether.

8. The method for preparing a temperature-sensitive catalyst for coupling reaction according to claim 5, wherein In step S1, the polymerization reaction temperature is 60-90° C., and the reaction time is 6-24 hours; In step S2, the polymerization reaction temperature is 60-90° C., and the reaction time is 6-24 hours; In step S3, the reaction temperature is 20-50° C., and the reaction time is 4-12 hours.

9. Use of the temperature-sensitive catalyst according to claim 1 in a coupling reaction, characterized in that: The coupling reaction catalyzed by the temperature-sensitive catalyst includes any one of a CC coupling reaction of an aryl halide with an aryl boronic acid compound, a CC coupling reaction of an aryl halide with a monosubstituted olefin, a CC coupling reaction of an aryl halide with a monosubstituted alkyne, and a CN coupling reaction of an aryl halide with an amine compound; The coupling reaction temperature is higher than the lowest critical solution temperature of the temperature-sensitive catalyst. After the coupling reaction is completed, the temperature is lowered to a temperature lower than the lowest critical solution temperature of the temperature-sensitive catalyst to recover the catalyst.

10. A method for a flow circulation catalytic coupling reaction, characterized in that: The steps include: The temperature-sensitive catalyst and alkaline salt described in claim 1 are dispersed in water to form a solution A, the coupling reaction raw materials are dispersed in a solvent to form a solution B, and the solution A and solution B are respectively injected into a microfluidic device to perform a flow circulation catalytic coupling reaction; The microfluidic device includes a first feed pump, a second feed pump, a mixer, a reactor and a separator, wherein the outlet of the first feed pump is connected to the feed port of the mixer for conveying solution A; the outlet of the second feed pump is connected to the feed port of the mixer for conveying solution B, the discharge port of the mixer, the reactor and the separator are sequentially connected, and a catalyst reflux pipe and a discharge pipe are provided in the separator, the catalyst reflux pipe is connected to the feed port of the first feed pump through a reflux pump, and the discharge pipe is used to discharge the coupling reaction product; The reaction temperature set in the reactor is higher than the lowest critical solution temperature of the temperature-sensitive catalyst, and the temperature set in the separator is lower than the lowest critical solution temperature of the temperature-sensitive catalyst.

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