Temperature-sensitive catalyst for coupling reaction as well as preparation method and application of temperature-sensitive catalyst

Abstract

The invention provides a temperature-sensitive catalyst for coupling reaction and a preparation method and application thereof, and belongs to the technical field of coupling reaction catalyst preparation, and the preparation method specifically comprises the following steps: mixing polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate, a nitrogen-phosphorus monomer and an auxiliary agent for reaction to generate a copolymer, and then complexing with a palladium compound to obtain the temperature-sensitive catalyst. The catalyst is formed by complexing a copolymer of three monomers and a palladium compound. Wherein the polyethylene glycol methyl ether methacrylate unit is used for ensuring the temperature sensitivity of the whole catalyst structure; modifying a methacrylate monomer with a small molecular nitrogen-phosphorus ligand and an organic amine auxiliary side group; and after complexing with a palladium compound, coordinating the nitrogen-phosphorus ligand with the palladium compound under the assistance of an intramolecular synergistic effect of an organic amine auxiliary agent, so as to prepare the polymer catalyst with multiple catalytic active sites.

Description

Technical Field

[0001] The invention relates to the technical field of coupling reaction catalyst preparation, and in particular to a temperature-sensitive catalyst for coupling reaction and a preparation method and application thereof. Background Art

[0002] Carbon-carbon bonds and carbon-hetero bonds are the basic structural units for building organic compounds. Transition metal-catalyzed coupling is currently one of the most effective and direct ways to build carbon-carbon bonds and carbon-hetero bonds. The precious metal catalysts used in such coupling reactions are usually not stable enough in air and water and are difficult to separate and recover.

[0003] Although linear polymer loading of precious metal catalysts is one of the solutions to the above-mentioned problems, compared with traditional homogeneous small molecule catalysts, linear polymer catalysts have high reusability, good stability, and are easy to separate from products. They can also catalyze organic synthesis reactions under reaction conditions that are difficult for some small molecule catalysts to achieve. At present, certain progress has been made in using linear polymer catalysts to assist metal-catalyzed coupling reactions. However, the catalytic active centers at the ends of the macromolecular chains are restricted by the segmental activity of the polymer skeleton, and their catalytic activity will be affected by the polymer matrix, making it impossible to efficiently catalyze coupling reactions. In addition, the use of excessive amounts of poor organic solvents to precipitate polymer catalysts is also a huge waste of chemical resources, which does not meet the requirements of efficient and green conversion strategies. In addition, traditional polymer catalysts for coupling reactions are usually limited by the complex operation and cumbersome steps of catalyst separation and recovery, which is contrary to the intelligent and automated synthesis methods.

[0004] Therefore, how to utilize the characteristics of polymer materials to optimize the catalytic performance and recovery methods of catalysts remains an important technical bottleneck currently faced. Summary of the invention

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

[0006] In the first aspect, the embodiments of the present application provide a temperature-sensitive catalyst for a coupling reaction, and 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 (5 to 20):(0 to 2):(2 to 5); m is an integer between 5 and 25.

[0007] In a second aspect, an embodiment of the present application provides a method for preparing a temperature-sensitive catalyst for a coupling reaction, the specific steps of which include: mixing polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate, nitrogen and phosphorus monomers and an auxiliary agent to generate 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: .

[0008] In the technical solution of the embodiment of the present application, Cy in the nitrogen-phosphorus monomer structural formula is a cyclohexyl group.

[0009] Preferably, the synthesis of nitrogen-phosphorus monomers comprises the following steps:

[0010] S1. Place o-bromobenzene azido (Compound 1), p-acetylene phenol, copper sulfate pentahydrate, and sodium ascorbate in a round-bottom flask, add methanol to completely dissolve them, introduce inert gas to deoxygenate, heat and stir to react, and obtain the first product (Compound 2) through post-treatment; S2, the first product, TBSCl and imidazole are placed in a round-bottom flask, and then dichloromethane is added to completely dissolve them, an inert gas is introduced to deoxygenate, and the hydroxyl protection reaction is performed by heating and stirring, and the second product (compound 3) is obtained by post-treatment; S3, put the second product into a Schlenk tube, add tetrahydrofuran to completely dissolve it, pass inert gas to remove oxygen, adjust the temperature to -78 °C, add n-butyl lithium and dicyclohexylphosphine chloride dropwise, adjust the temperature to room temperature for reaction. Then, remove the hydroxyl protecting group by tetrabutylammonium fluoride, and obtain the third product (compound 4) by post-treatment; S4. The third product and triethylamine are placed in a Schlenk tube, dichloromethane is added to completely dissolve them, an inert gas is introduced to deoxygenate, methacryloyl chloride is added dropwise in an ice-water bath to react for 4 hours, and nitrogen phosphorus monomer NPMA is obtained through post-treatment.

[0011] Preferably, the molar ratio of polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate and nitrogen-phosphorus monomer is (5-20): (0-2): (2-5).

[0012] 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).

[0013] Preferably, the method comprises the following steps: S1, after mixing polyethylene glycol methyl ether methacrylate, an initiator, a chain transfer agent, and a reaction solvent, introducing an inert gas to deoxygenate, 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 liquid, heating and stirring to carry out polymerization reaction to obtain a second reaction liquid, adding the second reaction liquid 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 the precipitation solvent, filtering and drying to obtain a temperature-sensitive catalyst.

[0014] In the technical solution of the embodiment of the present application, the structural formulas of the three monomers of polyethylene glycol methyl ether methacrylate (OEGMA), dimethylaminoethyl methacrylate (NMA) and nitrogen phosphorus monomer (NPMA) are as follows: , , .

[0015] The reaction formula of step S1 and step S2 is as follows (1): ; The reaction formula of step S3 is as follows (2): .

[0016] 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.

[0017] 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.

[0018] 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, ethyl ether, and petroleum ether.

[0019] Preferably, the polymerization reaction temperature in step S1 is 60-90° C., and the reaction time is 6-24 h; In step S2, the polymerization reaction temperature is 60-90° C., and the reaction time is 6-24 h; In step S3, the reaction temperature is 20-50° C. and the reaction time is 4-12 h.

[0020] Preferably, in step S3, the molar ratio of palladium atoms in the palladium compound to phosphorus atoms in the copolymer is 1:(1-2), the reaction temperature is 20-50° C., and the reaction time is 4-12 h.

[0021] In a third aspect, an embodiment of the present application provides an application of a temperature-sensitive catalyst for a coupling reaction, wherein 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 can be lowered to a temperature lower than the lowest critical solution temperature of the temperature-sensitive catalyst to recover the catalyst.

[0022] In a fourth aspect, the present application provides a method for a flow cycle catalytic coupling reaction, comprising the following steps: The temperature-sensitive catalyst and the alkaline salt 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 the solution B are respectively injected into a microfluidic device to perform a flow cycle 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; 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 the 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.

[0023] Different from the existing technical solutions, the beneficial effects of this application include: The present application provides a thermosensitive polymer catalyst, which is a copolymer of three monomers, POEGMA-bP (NPMA-co-NMA), and a palladium compound. Among them, the polyethylene glycol methyl ether methacrylate (POEGMA) unit is mainly to ensure the thermosensitivity of the entire catalyst structure; and by modifying the small molecule nitrogen-phosphorus ligand and the organic amine auxiliary side group to the methacrylate monomer, the P (NPMA-co-NMA) fragment of the polymer is loaded with small molecule nitrogen-phosphorus ligands and organic amine auxiliary agents; after complexing with the palladium compound, the nitrogen-phosphorus ligand and the palladium compound are coordinated by the intramolecular synergistic effect of the organic amine auxiliary agent to prepare a polymer catalyst with multiple catalytic active sites. In the relevant performance test, it was found that the catalyst can be used to catalyze the coupling reaction of aromatic halides. As a thermosensitive polymer structure, the POEGMA fragment has a specific minimum critical solution temperature (LCST) in a solution of water and toluene phases, so that the polymer catalyst can return to the water phase by adjusting the temperature after the heating catalytic reaction is completed, thereby realizing the catalyst recycling. This temperature sensitivity is combined with microfluidic technology to achieve flow-cycle catalysis of aromatic halide coupling reactions.

[0024] The above description is only an overview of the technical solution of the present application. In order to more clearly understand the technical means of the present application, it can be implemented in accordance with the contents of the specification. In order to make the above and other purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are listed below. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solution of the present application, the following is a brief introduction to the drawings used in the present application. Obviously, the drawings described below are only some embodiments of the present application, and for ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0026] Figure 1 This is the H-NMR spectrum of the nitrogen-phosphorus monomer NPMA in Example 1 of the present application.

[0027] Figure 2 This is the structural formula of the temperature-sensitive catalyst in Example 2 of the present application.

[0028] Figure 3 This is an optical picture of the temperature-sensitive catalyst in Example 2 of the present application shuttling back and forth between the water phase and the toluene phase due to temperature response; 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°C; 3c is the position of the temperature-sensitive catalyst after cooling.

[0029] Figure 4 Schematic diagram of the microfluidic device in Example 12 of the present application.

[0030] Description of reference numerals: 1. First feed pump; 2. Second feed pump; 3. Mixer; 4. Reactor; 5. Separator; 6. Reflux pump. DETAILED DESCRIPTION

[0031] The following embodiments of the technical solution of the present application are described in detail in conjunction with the accompanying drawings. The following embodiments are only used to more clearly illustrate the technical solution of the present application, and are therefore only used as examples, and cannot be used to limit the scope of protection of the present application.

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by technicians in the technical field to which this application belongs; the terms used herein are only for the purpose of describing specific embodiments and are not intended to limit this application; the terms "including" and "having" in the specification and claims of this application and the above-mentioned figure descriptions and any variations thereof are intended to cover non-exclusive inclusions.

[0033] 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 "multiple" is more than two, unless otherwise clearly and specifically defined.

[0034] Reference to "embodiments" herein means that a particular feature, structure, or characteristic described in conjunction with the embodiments may be included in at least one embodiment of the present application. The appearance of the phrase in various locations in the specification does not necessarily refer to the same embodiment, nor is it an independent or alternative embodiment that is mutually exclusive with other embodiments. It is explicitly and implicitly understood by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0035] 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, indicating that there may be three relationships. For example, A and / or B can represent: A exists alone, A and B exist at the same time, and B exists alone. In addition, the character " / " in this article generally indicates that the associated objects before and after are in an "or" relationship.

[0036] In the description of the embodiments of the present application, the term "multiple" refers to more than two (including two). Similarly, "multiple groups" refers to more than two groups (including two groups), and "multiple pieces" refers to more than two pieces (including two pieces).

[0037] Carbon-carbon bonds and carbon-hetero bonds are the basic structural units for building organic compounds. Transition metal catalytic coupling is currently one of the most effective and direct ways to build carbon-carbon bonds and carbon-hetero bonds. The precious metal catalysts used in such coupling reactions are usually not stable enough in air and water and are difficult to separate and recycle. Although linear polymer loading of precious metal catalysts is one of the ways to solve the above problems, how to use the characteristics of polymer materials to optimize the catalytic performance and recovery methods of catalysts is still an important technical bottleneck currently faced.

[0038] In order to solve the problem that the noble metal catalysts in the prior art are not stable enough in air and water and are difficult to separate and recycle, the present application provides a thermosensitive 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 methacrylate monomer, so that the P(NPMA-co-NMA) fragment of the polymer is loaded with small molecule nitrogen-phosphorus ligand and organic amine auxiliary, and after complexing with the palladium compound, through the intramolecular synergistic effect of the organic amine auxiliary and the multi-catalytic active sites coordinated by the nitrogen-phosphorus ligand and the palladium compound, it is found in the relevant performance test that the catalyst can be used to catalyze the coupling reaction of aromatic halides. As a thermosensitive polymer structure, the POEGMA fragment has a specific minimum critical solution temperature (LCST) in a solution of water and toluene phases, so that the polymer catalyst can return to the water phase by adjusting the temperature after the heating catalytic reaction is completed, thereby realizing the catalyst recycling. And this thermosensitivity is combined with microfluidic technology to realize the flow circulation catalysis of the coupling reaction of aromatic halides.

[0039] In view of the technical problems existing in the background technology, the present application provides a temperature-sensitive catalyst for coupling reaction and its preparation method and application, aiming to solve the problem that precious metal catalysts in the prior art are not stable enough in air and water and are difficult to separate and recover.

[0040] In the first aspect, the embodiments of the present application provide a temperature-sensitive catalyst for a coupling reaction, and 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 (5 to 20): (0 to 2): (2 to 5); m is an integer between 5 and 25.

[0041] In the technical solution of the embodiment of the present application, when the ratio of x is too large, the polymer chain is too long, which will wrap the palladium catalyst and thus reduce the catalytic effect. When the ratio of x is too small, the molecular weight of the thermosensitive polymer fragment (POEGMA) is too small, the thermosensitive effect of the polymer is reduced, and it does not have the thermosensitive effect of entering the organic phase at high temperature and the aqueous phase at low temperature.

[0042] In a second aspect, an embodiment of the present application provides a method for preparing a temperature-sensitive catalyst for a coupling reaction, the specific steps of which include: mixing polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate, nitrogen and phosphorus monomers and an auxiliary agent to generate 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: .

[0043] ; The synthesis of nitrogen-phosphorus monomers includes the following steps: S1. Place o-bromobenzene azido (Compound 1), p-acetylene phenol, copper sulfate pentahydrate, and sodium ascorbate in a round-bottom flask, add methanol to completely dissolve them, introduce inert gas to deoxygenate, heat and stir to react, and obtain the first product (Compound 2) through post-treatment; S2, the first product, TBSCl and imidazole are placed in a round-bottom flask, and then dichloromethane is added to completely dissolve them, an inert gas is introduced to deoxygenate, and the hydroxyl protection reaction is performed by heating and stirring, and the second product (compound 3) is obtained by post-treatment; S3, put the second product into a Schlenk tube, add tetrahydrofuran to completely dissolve it, pass inert gas to remove oxygen, adjust the temperature to -78 °C, add n-butyl lithium and dicyclohexylphosphine chloride dropwise, adjust the temperature to room temperature for reaction. Then, remove the hydroxyl protecting group by tetrabutylammonium fluoride, and obtain the third product (compound 4) by post-treatment; S4. The third product and triethylamine are placed in a Schlenk tube, dichloromethane is added to completely dissolve them, an inert gas is introduced to deoxygenate, methacryloyl chloride is added dropwise in an ice-water bath to react for 4 hours, and nitrogen phosphorus monomer NPMA is obtained through post-treatment.

[0044] In the technical solution of the embodiment of the present application, Cy in the nitrogen-phosphorus monomer structural formula is a cyclohexyl group.

[0045] Preferably, the molar ratio of polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate and nitrogen-phosphorus monomer is (5-20): (0-2): (2-5).

[0046] 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).

[0047] Preferably, the method comprises the following steps: S1, after mixing polyethylene glycol methyl ether methacrylate, an initiator, a chain transfer agent, and a reaction solvent, introducing an inert gas to deoxygenate, 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 liquid, heating and stirring to carry out polymerization reaction to obtain a second reaction liquid, adding the second reaction liquid 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 the precipitation solvent, filtering and drying to obtain a temperature-sensitive catalyst.

[0048] In the technical solution of the embodiment of the present application, the structural formulas of the three monomers of polyethylene glycol methyl ether methacrylate (OEGMA), dimethylaminoethyl methacrylate (NMA) and nitrogen phosphorus monomer (NPMA) are as follows: , , .

[0049] The reaction formula of step S1 and step S2 is as follows (1): ; The reaction formula of step S3 is as follows (2): .

[0050] 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.

[0051] 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.

[0052] 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, ethyl ether, and petroleum ether.

[0053] Preferably, the polymerization reaction temperature in step S1 is 60-90° C., and the reaction time is 6-24 h; In step S2, the polymerization reaction temperature is 60-90° C., and the reaction time is 6-24 h; In step S3, the reaction temperature is 20-50° C. and the reaction time is 4-12 h.

[0054] Preferably, in step S3, the molar ratio of palladium atoms in the palladium compound to phosphorus atoms in the copolymer is 1:(1-2), the reaction temperature is 20-50° C., and the reaction time is 4-12 h.

[0055] In a third aspect, an embodiment of the present application provides an application of a temperature-sensitive catalyst for a coupling reaction, wherein 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 can be lowered to a temperature lower than the lowest critical solution temperature of the temperature-sensitive catalyst to recover the catalyst.

[0056] In a fourth aspect, the present application provides a method for a flow cycle catalytic coupling reaction, comprising the following steps: The temperature-sensitive catalyst and the alkaline salt 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 the solution B are respectively injected into a microfluidic device to perform a flow cycle 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; 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 the 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.

[0057] Some specific embodiments are listed below. It should be noted that the embodiments described below are exemplary and are only used to explain the present application, and should not be construed as limiting the present application. If specific techniques or conditions are not specified in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. The reagents or instruments used without specifying the manufacturer are all conventional products that can be obtained commercially.

[0058] 1. Preparation method Example 1 A preparation method for synthesizing temperature-sensitive catalyst monomer NPMA Weigh o-bromobenzene azido (1.1782 g), p-acetylene phenol (1.2762 g), copper sulfate pentahydrate (0.045 g), and sodium ascorbate (0.4458 g) into a 100 mL round-bottom flask, then add 12 mL of methanol to completely dissolve it, then add 6 mL of water, and react at 40 °C in a nitrogen atmosphere for 8 h. After the reaction, add 25 mL of ethyl acetate, wash three times with 20 mL of water and saturated brine, dry over anhydrous sodium sulfate, evaporate and concentrate the organic phase, and purify it on a silica gel column to obtain 1.03 g of the first product (compound 1) (yield 55%).

[0059] The first product (compound 2) (0.6 g), TBSCl (0.3718 g) and imidazole (0.1680 g) were weighed and placed in a 100 mL round-bottom flask, and then 12 mL of dichloromethane was added to completely dissolve them, and the mixture was reacted at 30 °C in a nitrogen atmosphere for 4 h. After the reaction, 25 mL of dichloromethane was added, and the mixture was washed three times with 20 mL of water and saturated brine, dried over anhydrous sodium sulfate, and the organic phase was evaporated and concentrated, and then purified by silica gel column to obtain 0.76 g of the second product (compound 3) (yield 96%).

[0060] The second product (Compound 3) (0.4 g) was weighed and placed in a 25 mL Schlenk tube, 4 mL of tetrahydrofuran was added to completely dissolve it, the temperature was adjusted to -78 °C under nitrogen atmosphere, 2.5 mol / L n-butyl lithium (0.5019 mL) was added dropwise, and dicyclohexylphosphine chloride (0.6736 g) was added dropwise after 30 min, and the temperature was adjusted to room temperature for reaction for 8 h. The reaction temperature was then adjusted to room temperature, 1 mol / L tetrabutylammonium fluoride (1.4478 mL) was added and reacted for 4 h. After the reaction was completed, 25 mL of ethyl acetate was added, and the mixture was washed three times with 20 mL of water and saturated brine, 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%).

[0061] The third product (compound 4) (0.34 g) and triethylamine (0.1588 g) were weighed and placed in a 25 mL Schlenk tube, and then 5 mL of dichloromethane was added to completely dissolve it. Methacryloyl chloride (0.1639 g) was added dropwise under a nitrogen atmosphere and ice-water bath to react for 4 h. After the reaction, 25 mL of dichloromethane was added, and the mixture was washed three times with 20 mL of water and saturated brine, respectively, dried over anhydrous sodium sulfate, and the organic phase was evaporated and concentrated. After purification by a silica gel column, 0.36 g of the product nitrogen phosphorus monomer NPMA (yield 91%) was obtained. The H NMR spectrum was as follows Figure 1 shown.

[0062] Example 2 A method for preparing a temperature-sensitive catalyst for coupling reaction: Weigh OEGMA 950 (950 mg) and azobisisobutyronitrile 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 dimethyl sulfoxide (DMSO) was added to completely dissolve it, and heated at 70 ° C in a nitrogen atmosphere for 24 h. Then NMA (31 mg) and the nitrogen phosphorus monomer NPMA (245 mg) prepared in Example 1 were weighed and dissolved in 1 mL of DMSO and added, and heated at 70 ° C in a nitrogen atmosphere for 24 h. After the reaction was completed, the reaction solution was dripped into 100 mL of cold methyl tert-butyl ether, a precipitation solvent, and solids were precipitated, which were filtered to obtain POEGMA. 950 - b- P(NPMA- co- NMA) (x:y:z = 10:2:5 light yellow filter cake). Under nitrogen atmosphere, 175 mg of copolymer and 16 mg of palladium acetate were added with 2 mL of toluene into a reaction vessel and stirred at 50 °C for 2 h to obtain a thermosensitive catalyst with the following structural formula: Figure 2 shown.

[0063] Example 3 A method for preparing a temperature-sensitive catalyst for coupling reaction: Weigh 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, and then 2 mL of dimethylacetamide (DMF) was added to completely dissolve it, and heated to 80 ° C in a nitrogen atmosphere for 12 h. Then NMA (16 mg) and the nitrogen phosphorus monomer NPMA (245 mg) prepared in Example 1 were weighed and dissolved in 1 mL of DMF and added, and heated to 70 ° C in a nitrogen atmosphere for 12 h. After the reaction was completed, the reaction solution was dripped into 100 mL of cold ether, and solids precipitated, which were filtered to obtain POEGMA. 950 - b- P(NPMA- co- NMA) (x:y:z = 10:1:5 light yellow filter cake). Under nitrogen atmosphere, 169 mg of copolymer and 16 mg of Pd2(Dba)3 were added with 2 mL of toluene into a reaction vessel and stirred at 40 °C for 4 h to obtain a thermosensitive catalyst.

[0064] Example 4 A method for preparing a temperature-sensitive catalyst for coupling reaction: Weigh 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, and then 2 mL DMSO was added to completely dissolve them, and the mixture was heated at 60 °C in a nitrogen atmosphere for 24 h. Then NMA (16 mg) and the nitrogen phosphorus monomer NPMA (245 mg) prepared in Example 1 were weighed and dissolved in 1 mL DMSO and added, and the mixture was heated at 60 °C in a nitrogen atmosphere for 24 h. After the reaction was completed, the reaction solution was dripped into 100 mL of cold methyl tert-butyl ether, and solids were precipitated, which were filtered to obtain POEGMA. 950 - b- P(NPMA- co- NMA) (x:y:z = 5:1:5 light yellow filter cake). Under nitrogen atmosphere, 102 mg of copolymer and 16 mg of Pd2(Dba)3 were added with 2 mL of toluene into a reaction vessel and stirred at 30 °C for 6 h to obtain a thermosensitive catalyst.

[0065] Example 5 A method for preparing a temperature-sensitive catalyst for coupling reaction: 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 DMF was added to completely dissolve it, and heated at 90 °C in a nitrogen atmosphere for 8 h. Then NMA (32 mg) and the nitrogen phosphorus monomer NPMA (98 mg) prepared in Example 1 were weighed and dissolved in 1 mL DMF and added, and heated at 60 °C in a nitrogen atmosphere for 8 h. After the reaction was completed, the reaction solution was dripped into 100 mL of cold ether, and solid precipitated, which was filtered to obtain POEGMA. 950 - b- P(NPMA- co- NMA) (x:y:z = 5:2:2 pale yellow filter cake). Under nitrogen atmosphere, 215 mg of copolymer and 8 mg of palladium acetate were added with 2 mL of toluene into a reaction vessel and stirred at 40 °C for 4 h to obtain a thermosensitive catalyst.

[0066] Example 6 Weigh OEGMA 950(950 mg) and dibenzoyl peroxide (24 mg) and 2-[[(hexylthio)thiocarbonyl]thio]-propionic acid (27 mg) were placed in a 25 mL Schlenk tube, and then 2 mL of dimethyl sulfoxide (DMSO) was added to completely dissolve them, and heated at 70 °C in a nitrogen atmosphere for 24 h. Then NPMA (245 mg) was weighed and dissolved in 1 mL of DMSO and added, and heated at 70 °C in a nitrogen atmosphere for 24 h. After the reaction was completed, the reaction solution was dripped into 100 mL of cold petroleum ether, a precipitation solvent, and solids were precipitated, which were filtered to obtain POEGMA. 950 - b- P(NPMA) (x:y:z = 10:0:5 light yellow filter cake). Under nitrogen atmosphere, 175 mg of copolymer and 16 mg of palladium acetate were added with 2 mL of toluene into a reaction vessel and stirred at 50 °C for 2 h to obtain a thermosensitive catalyst.

[0067] Example 7 Take 0.4 mg of the catalyst prepared in Example 2, 244 mg of cesium carbonate and 125 mg of p-methoxyphenylboronic acid, and 118 mg of bromobenzene, dissolve in 0.2 mL of toluene and 0.8 mL of water, and react at 70°C for 2 h. After the reaction is completed, the temperature drops to room temperature, the reaction product is in the organic phase, and the catalyst is in the lower aqueous phase. Take the upper organic phase, and the aqueous phase containing the catalyst is directly used for the second reaction. Add 244 mg of cesium carbonate, 125 mg of p-methoxyphenylboronic acid, 118 mg of bromobenzene and 0.2 mL of toluene, and react at 80°C for 2 h. Repeat the reaction twice. The coupling reaction equation of p-methoxyphenylboronic acid and bromobenzene is as follows: .

[0068] Example 8 0.4 mg of the catalyst prepared in Example 2, 244 mg of cesium carbonate, 86 mg of styrene, 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 5 h.

[0069] The coupling reaction equation of styrene and bromobenzene is as follows: .

[0070] Example 9 0.4 mg of the catalyst prepared in Example 2, 104 mg of potassium carbonate, 84 mg of phenylacetylene, 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 5 h.

[0071] The coupling reaction equation of phenylacetylene and bromobenzene is as follows: .

[0072] Example 10 0.4 mg of the catalyst prepared in Example 2, 104 mg of potassium carbonate, 96 mg of phenylethylamine, 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 8 h. The conversion rate was detected by gas chromatography.

[0073] The coupling reaction equation of phenylethylamine and bromobenzene is as follows: .

[0074] Embodiment 11 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: .

[0075] Example 12 Microfluidic devices are used to realize flow cycle catalytic coupling reactions, such as Figure 4 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 minimum critical solution temperature of the temperature-sensitive catalyst, and the temperature set in the separator 4 is lower than the minimum critical solution temperature of the temperature-sensitive catalyst. The separator 4 is provided with a catalyst reflux pipe and a discharge pipe, and 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 water phase, and is recycled through the reflux pipe set in the water phase; the organic phase and the product without the catalyst are discharged along the discharge pipe.

[0076] 5 mg of the catalyst prepared in Example 2 and potassium carbonate (1.38 g) 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 4As shown, solutions A and B are transferred to syringes respectively and fixed on the first feed pump 1 and the second feed pump 2. The entire flow path is rinsed with toluene phase in advance, and solutions A and B are continuously input into the reactor 4 through the first feed pump 1 and the second feed pump 2. The temperature of the reactor 4 is 70°C, and the catalyst is transferred to the toluene phase containing the coupling reaction raw materials for catalytic reaction. The flow rates of solutions A and B are controlled to be 40 µL / min and 10 µL / min, respectively. The temperature in the separator 4 is room temperature. After 3 hours of reaction, all organic phases are separated and the aqueous phase is extracted with ethyl acetate. The organic phase is collected and dried, concentrated to remove the solvent, and the obtained crude product is purified by column chromatography to obtain the target product.

[0077] Comparative Example 1 Take 0.4 mg of common coupling reaction catalyst (triphenylphosphine) palladium, 244 mg of cesium carbonate and 125 mg of p-methoxyphenylboronic acid, and 118 mg of bromobenzene and dissolve them in 0.5 mL of toluene, and react at 70°C for 2 h.

[0078] Comparative Example 2 Weigh OEGMA 950 (950 mg) and azobisisobutyronitrile 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 dimethyl sulfoxide (DMSO) was added to completely dissolve it, and heated at 70 ° C in a nitrogen atmosphere for 24 h. Then NMA (31 mg) was weighed and dissolved in 1 mL of DMSO and added, and heated at 70 ° C in a nitrogen atmosphere for 24 h. After the reaction was completed, the reaction solution was dripped into 100 mL of cold methyl tert-butyl ether, a precipitation solvent, and solid precipitated, which was filtered to obtain POEGMA. 950 - b- P(NMA) (x:y:z = 10:2:0 light yellow filter cake). Because the polymer lacks phosphorus ligands, it cannot complex with palladium acetate and cannot generate a temperature-sensitive catalyst.

[0079] Comparative Example 3 Weigh OEGMA 950 (950 mg) and azobisisobutyronitrile 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 dimethyl sulfoxide (DMSO) was added to completely dissolve it, and heated at 70 ° C in a nitrogen atmosphere for 24 h. Then NMA (155 mg) and NPMA (245 mg) were weighed and dissolved in 1 mL of DMSO and added, and heated at 70 ° C in a nitrogen atmosphere for 24 h. After the reaction was completed, the reaction solution was dripped into 100 mL of cold methyl tert-butyl ether, a precipitation solvent, and solids were precipitated, which were filtered to obtain POEGMA. 950- b- P(NPMA- co- NMA) (x:y:z = 10:10:5 light yellow filter cake). The temperature sensitivity test showed that the temperature sensitivity of the polymer disappeared because the x:y ratio was too large (1:1).

[0080] Comparative Example 4 Weigh OEGMA 950 (950 mg) and azobisisobutyronitrile 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 dimethyl sulfoxide (DMSO) was added to completely dissolve it, and heated at 70 ° C in a nitrogen atmosphere for 24 h. Then NMA (31 mg) and NPMA (490 mg) were weighed and dissolved in 1 mL of DMSO and added, and heated at 70 ° C in a nitrogen atmosphere for 24 h. After the reaction was completed, the reaction solution was dripped into 100 mL of cold methyl tert-butyl ether, a precipitation solvent, and solids were precipitated, which were filtered to obtain POEGMA. 950 - b- P(NPMA- co- NMA) (x:y:z = 10:2:10 light yellow filter cake). The temperature sensitivity test showed that the temperature sensitivity of the polymer disappeared because the x:z ratio was too large (1:1).

[0081] Comparative Example 5 Weigh OEGMA 950 (1900 mg) and azobisisobutyronitrile AIBN (32 mg) and 2-[[(hexylthio)thiocarbonyl]thio]-propionic acid (27 mg) were placed in a 25 mL Schlenk tube, and then 2 mL of dimethyl sulfoxide (DMSO) was added to completely dissolve it, and heated at 70 ° C in a nitrogen atmosphere for 24 h. Then NMA (16 mg) and NPMA (98 mg) were weighed and dissolved in 1 mL of DMSO and added, and heated at 70 ° C in a nitrogen atmosphere for 24 h. After the reaction was completed, the reaction solution was dripped into 100 mL of cold methyl tert-butyl ether, a precipitation solvent, and solids were precipitated, which were filtered to obtain POEGMA. 950 - b- P(NPMA- co- NMA) (x:y:z = 20:1:2 light yellow filter cake). Under nitrogen atmosphere, 800 mg of copolymer and 16 mg of palladium acetate were added with 2 mL of toluene into a reaction vessel and stirred at 50 °C for 2 h to obtain a thermosensitive catalyst.

[0082] Comparative Example 6 0.4 mg of the catalyst prepared in Comparative Example 5, 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: .

[0083] II. Analysis of test results of various embodiments and comparative examples (1) Pour water and toluene into a test tube in sequence, add the temperature-sensitive catalyst prepared in Example 2 into the test tube, and observe the changes of the catalyst at different temperatures. Figure 3 It can be seen from a that at room temperature the catalyst is in the water phase; when the test tube is heated to 70°C, Figure 3 b, the catalyst is transferred from the water phase to the toluene phase and dissolved in the toluene phase; after the test tube is cooled to room temperature, Figure 3 c, the catalyst returns from the toluene phase to the water phase. It can be seen that the catalyst obtained in Example 2 can shuttle back and forth between the water and toluene phases by adjusting the temperature, which is convenient for the recovery and utilization of the catalyst.

[0084] (2) The conversion rate of the first coupling reaction in Example 7 and the conversion rates of the coupling reactions in Examples 8 to 11 and Comparative Examples 1 and 6 were detected by gas chromatography. The detection results are shown in Table 1 below.

[0085] Table 1 Coupling reaction conversion rate test data of each embodiment and comparative example

[0086] As can be seen from Table 1, the temperature-sensitive catalyst prepared by the method of Example 2 can catalyze various coupling reactions and obtain a conversion rate of more than 90%. In Example 11, the temperature-sensitive catalyst prepared in Example 6 has a low catalytic activity in the coupling reaction, which indicates that the nitrogen-phosphorus monomer is used for complexing palladium catalyst, and dimethylaminoethyl methacrylate is used as an amine auxiliary agent to assist the phosphorus ligand complexing palladium catalyst in the nitrogen-phosphorus monomer, and the catalyst prepared by the synergistic effect of the two can obtain a better catalytic effect.

[0087] The yield of the common catalyst in Comparative Example 1 is only 86%, and the palladium in this catalyst cannot be recovered, so the cost is relatively high.

[0088] In Comparative Example 2, no nitrogen-phosphorus monomer was used, and a temperature-sensitive catalyst could not be synthesized. In Comparative Example 3, the y:x ratio was too large, and the amount of dimethylaminoethyl methacrylate added was too high. In Comparative Example 4, the z:x ratio was too large, and the amount of nitrogen-phosphorus monomer added was too high. The temperature sensitivity of the catalysts in Comparative Examples 3 and 4 disappeared, indicating that when the x ratio was too small, the molecular weight of the thermosensitive polymer fragment (POEGMA) was too small, the temperature sensitivity effect of the polymer decreased, and it did not have the temperature-sensitive effect of entering the organic phase at high temperature and the aqueous phase at low temperature.

[0089] In Comparative Example 6, the catalyst prepared in Comparative Example 5 was used, and the conversion rate of the coupling reaction was greatly reduced, indicating that when the x ratio was too large, the polymer chain was too long and would wrap the palladium catalyst, resulting in a decrease in the catalytic effect.

[0090] (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.

[0091] Table 2 Coupling reaction conversion rate test data after catalyst recycling

[0092] It can be seen from Table 2 that after the catalyst is recycled for multiple times, a high coupling reaction conversion rate can still be maintained.

[0093] It should be noted that the present application is not limited to the above-mentioned embodiments. The above-mentioned embodiments are only examples, and the embodiments having the same structure as the technical idea and exerting the same effect within the scope of the technical solution of the present application are all included in the technical scope of the present application. In addition, without departing from the scope of the main purpose of the present application, various modifications that can be thought of by those skilled in the art to the embodiments and other methods of combining 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 (5 to 20): (0 to 2): (2 to 5); m is an integer between 5 and 25.

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

4. The method for preparing a temperature-sensitive catalyst for coupling reaction according to claim 2, characterized in that: The molar ratio of polyethylene glycol methyl ether methacrylate, dimethylaminoethyl methacrylate and nitrogen and phosphorus monomers is (5-20): (0-2): (2-5); 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 coupling reaction according to any one of claims 2 to 4, characterized in that: 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 deoxygenate, 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 liquid, heating and stirring to carry out polymerization reaction to obtain a second reaction liquid, adding the second reaction liquid 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 the 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, characterized in that: 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, characterized in that: 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, ethyl ether, and petroleum ether.

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

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 can be 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 cycle catalytic coupling reaction, characterized in that: The steps include: Dispersing the temperature-sensitive catalyst and alkaline salt described in claim 1 in water to form solution A, dispersing the coupling reaction raw materials in a solvent to form solution B, and injecting the solution A and solution B into a microfluidic device respectively to perform a flow cycle 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 connected in sequence, 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 the 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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