A method and apparatus for column flow continuous coupling reactions based on pickering emulsions

Abstract

The application is suitable for the technical field of coupling reaction, and provides a method and device for column flow continuous coupling reaction based on Pickering emulsion, wherein the method comprises the following steps: performing wetting activation treatment on graphene oxide under alkaline condition through an activation agent; under high-speed stirring condition, performing sufficient mixing of the obtained graphene oxide with interface activity and a catalyst under the action of an organic solvent; loading the obtained Pickering emulsion of the solid-supported catalyst into a column reactor, continuously feeding aryl halide and boric acid compound from the lower part of the column reactor, and continuously feeding carbonate from the upper part of the column reactor to perform coupling reaction. The application provides a new method for column flow continuous coupling reaction of the solid-supported catalyst, the reaction system is stable, the problems such as the collection of products by demulsification / emulsification are not needed, the operation is simple and easy to implement, the conditions are mild, the method is suitable for most coupling reactions, and is easy to implement large-scale production.

Description

Technical Field

[0001] This application belongs to the field of coupling reaction technology, and particularly relates to a method and apparatus for continuous coupling reaction based on Pickering emulsion in column flow. Background Technology

[0002] The Suzuki coupling reaction was first reported in 1981 by Suzuki et al. (Miyaura N, Suzuki AA Convenientstereospecific synthesis of α,β-unsaturated carboxylic esters via the palladium-catalyzed carbonylation of 1-alkenylboranes[J]. Chemistry Letters, 1981, 10(7): 879-882.). It can efficiently promote the reaction of aryl halides and borate compounds under Pd catalysis to form C-C bonds and obtain the target product. It has advantages such as mild reaction conditions, high conversion rate, and environmental friendliness, and is one of the most widely used synthetic methods for polymers and pharmaceuticals.

[0003] However, the Suzuki coupling reaction suffers from problems such as insufficient mass transfer resistance between the substrate and the basic substance, leading to incomplete reaction, and complex product separation and purification processes. Therefore, developing solvent systems with large interfacial areas is crucial. Recent studies have shown that Pickering emulsions are oil-water two-phase systems stabilized by amphiphilic solid particles, possessing advantages such as high stability, large interfacial area, low preparation cost, and environmental friendliness. Hiebler et al. (Hiebler K, Lichtenegger GJ, Maier MC, et al. Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry[J]. Beilstein journal of organic chemistry, 2018, 14(1):648-658.) synthesized a heterogeneous Ce-Sn-Pd compound. Furthermore, using the Pickering emulsion stabilized by this compound, they achieved the catalytic Suzuki coupling reaction of phenylboronic acid and various bromoaromatic hydrocarbons, increasing the contact area between reactants, reducing mass transfer resistance, and achieving highly efficient catalysis of the product. Although the use of Pickering emulsions in Suzuki coupling reactions has made some progress in recent years, it is difficult to achieve large-scale production because the product needs to be collected through a cycle of demulsification / emulsification of responsive Pickering emulsions under stimulation by pH, magnetic field, temperature, light and CO2.

[0004] Therefore, it is evident that existing Pickering emulsions used in Suzuki coupling reactions present challenges in product collection and continuous, large-scale production. Summary of the Invention

[0005] The purpose of this application is to provide a method for continuous column flow coupling reaction based on Pickering emulsion, which aims to solve the problem that existing Pickering emulsions used in Suzuki coupling reactions are difficult to collect products and difficult to achieve continuous and large-scale production.

[0006] This application embodiment is implemented as follows: a method for continuous coupling reaction of column flow based on Pickering emulsion includes:

[0007] Graphene oxide is wetted and activated under alkaline conditions with an activating agent to obtain graphene oxide with interfacial activity.

[0008] Under high-speed stirring conditions, the interfacially active graphene oxide and the catalyst are thoroughly mixed in the presence of an organic solvent to obtain a Pickering emulsion of the supported catalyst.

[0009] The Pickering emulsion of the supported catalyst is loaded into a column reactor, and aryl halides and boric acid compounds are continuously introduced from the bottom of the column reactor, while carbonates are continuously introduced from the top of the column reactor to carry out a coupling reaction.

[0010] Another objective of this application is to provide an apparatus for a continuous coupling reaction of column flow based on Pickering emulsion, the apparatus being the aforementioned column reactor, comprising a reactor body.

[0011] A filter plate, disposed inside the reactor body, is used to separate the oil-soluble product, Pickering emulsion, and carbonate aqueous solution; an oil-soluble product outlet and a carbonate aqueous solution inlet are disposed above the reactor body; and a carbonate aqueous solution outlet and an oil-soluble reactant inlet are disposed below the reactor body.

[0012] This application provides a novel method for continuous column-flow coupling reactions using supported catalysts. It eliminates the need for demulsification / emulsification to collect products, offering a simple and easy-to-operate method with mild conditions, suitable for most coupling reactions, and easy for large-scale production. Furthermore, the catalyst immobilization process used in this application is simple and highly efficient, maximizing catalyst integrity and activity. Additionally, the reactants in the oil phase and the catalyst on the oil phase or emulsifier particles can fully contact the alkaline substances in the aqueous solution, solving the mass transfer problem in the oil-water two-phase system, thereby improving catalytic efficiency and reducing reaction costs. Simultaneously, the reaction system is highly stable, allowing the catalytic reaction to operate continuously for over 3000 hours. Attached Figure Description

[0013] Figure 1 This is a schematic diagram of a continuous coupling reaction based on Pickering emulsion in a column flow, provided in an embodiment of this application. Detailed Implementation

[0014] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0015] The aryl halides and borate compounds that react in the Suzuki reaction are soluble only in organic solvents, while the basic substances (K₂CO₃ or Na₂CO₃ needs to be added during the reaction to promote the metallotransfer process and ensure the smooth progress of the reaction) are soluble in aqueous solutions. Therefore, there are problems such as mass transfer resistance between the reaction substrate and the basic substances, leading to incomplete reactions, and the product separation and purification process being relatively complex. To address the problems of product collection difficulties and the inability to achieve continuous and large-scale production when using Pickering emulsions for Suzuki coupling reactions, this application provides a new type of supported catalyst for continuous column flow coupling reactions. The proposed method eliminates the need for product collection through demulsification / emulsification, is simple and easy to operate, operates under mild conditions, is suitable for most coupling reactions, and is easy to scale up. Furthermore, the catalyst immobilization process used in this application is simple and highly efficient, maximizing catalyst integrity and activity. Moreover, the reactants in the oil phase and the catalyst on the oil phase or emulsifier particles can fully contact the alkaline substances in the aqueous solution, solving the mass transfer problem in the oil-water two-phase system, thereby improving the catalyst's catalytic efficiency and reducing reaction costs. Simultaneously, the reaction system is highly stable, and the catalytic reaction can operate continuously for over 3000 hours.

[0016] In this embodiment of the application, the method for continuous column flow coupling reaction based on Pickering emulsion includes the following steps:

[0017] In step S1, graphene oxide is wetted and activated under alkaline conditions with an activator to obtain graphene oxide with interfacial activity.

[0018] Optionally, graphene oxide is dispersed in deionized water, and after ultrasonic treatment with a wetting activator under alkaline conditions, it is mixed in a water bath at 60–90°C, and then washed and dried to obtain graphene oxide with interfacial activity.

[0019] In this embodiment, graphene oxide is used as an emulsifier. Comparing the Brodie, Staudenmaier, and Hummers methods, this application selects the Hummers method to prepare graphene oxide (GO) because it is the mildest method and allows for adjustments to experimental conditions to produce more complete graphene oxide. For example, an optional method is as follows: 5g of graphite is poured into a 1L beaker, 130mL of concentrated sulfuric acid is added and stirred, followed by the addition of 2.5g of sodium nitrate. The mixture is stirred for 2 hours in an ice-water bath. 15g of potassium permanganate is pre-ground into powder and added to the reaction system at a uniform rate (within 3 hours) after stirring for 2 hours, maintaining the system temperature at 0-5℃. The system temperature is then raised to 35℃, and 230mL of deionized water is slowly added, with continuous stirring for 1 hour. The system temperature is then raised to 98℃ and stirred for 30 minutes. Turn off the heating, add 400 mL of deionized water, and after the oxidation reaction is complete, add a certain amount of dilute hydrochloric acid and hydrogen peroxide to remove unreacted K2MnO4. Stir for 1 hour and then let stand. Centrifuge the system until neutral and store as GO.

[0020] The wetting activator is one or more of N,N-diethylethylenediamine, N,N-diethyl-1,3-propanediamine (NDEP), guanidinobutylamine sulfate, and hexylamine. Since the reaction environment in this embodiment is alkaline, graphene oxide, as an emulsifier, is difficult to form a stable Pickering emulsion under alkaline conditions. Therefore, this embodiment modifies graphene oxide with a wetting activator to change its surface wettability, thereby enabling it to form a stable Pickering emulsion under alkaline and high-temperature conditions.

[0021] In step S2, under high-speed stirring conditions, the interfacially active graphene oxide and the catalyst are thoroughly mixed in the presence of an organic solvent to obtain a Pickering emulsion of the supported catalyst.

[0022] In the embodiments of this application, taking the Suzuki coupling reaction as an example, different Pickering emulsions with immobilized catalysts are prepared according to the different positions of the catalyst in different Suzuki coupling reactions. That is, the positions of the catalyst in different Suzuki coupling reactions are different, and it may be loaded on the emulsifier or dispersed in the dispersion medium.

[0023] Optionally, if the catalyst is supported, the interfacially active graphene oxide is ultrasonically dispersed in an aqueous solution, and the catalyst, polyvinylpyrrolidone, and sodium borohydride are added sequentially and mixed thoroughly. After drying, the mixture is dispersed in deionized water and ultrasonically dispersed again. An organic solvent is added, and the mixture is stirred at high speed to obtain a Pickering emulsion of the supported catalyst. If the catalyst is dispersed in a dispersion medium, the interfacially active graphene oxide is ultrasonically dispersed in an aqueous solution, and a mixture of the catalyst and organic solvent is added. The mixture is stirred at high speed to obtain a Pickering emulsion of the supported catalyst.

[0024] The organic solvent, as the oil phase, can be one of the organic solvents that are immiscible with water, such as toluene or alkanes.

[0025] The catalyst can be a Pd-based catalyst or a bimetallic catalyst composed of a Pd-based catalyst and other metal-based catalysts such as Ni-based catalysts. The types used can be Na2PdCl4, Pd[P(C6H5)3]4, Ni(NO3)2·6H2O, etc.

[0026] Optionally, a high-speed shearing machine is used for high-speed mixing, with a mixing speed of 5000-1000 rpm and a mixing time of 1-3 min.

[0027] In step S3, the Pickering emulsion of the supported catalyst is loaded into a column reactor, and aryl halides and boric acid compounds are continuously introduced from the bottom of the column reactor, while carbonates are continuously introduced from the top of the column reactor to carry out a coupling reaction.

[0028] The aryl halide can be one or more of bromobenzene, iodobenzene, and chlorobenzene.

[0029] The boric acid compound may be one or more of phenylboronic acid, 2-methoxyphenylboronic acid, 2-methylphenylboronic acid, 4-methylphenylboronic acid, and 4-methoxyiodobenzene.

[0030] The carbonate is one or more of Na2CO3, NaHCO3, K2CO3, KHCO3, and Li2CO3.

[0031] The temperature of the column reactor is 60–90°C; the flow rate of the column reactor is 2–10 mL / h, and the flow rate can be precisely controlled by a peristaltic pump.

[0032] It is worth noting that most of the embodiments in this application take the Suzuki coupling reaction as an example, that is, using graphite oxide materials as emulsifiers to stabilize the water-oil emulsion system. The Suzuki coupling reaction is illustrated in a continuous flow reaction in a solvent with an oil / water interface. However, this should not limit the scope of this application. The column flow continuous coupling reaction method based on Pickering emulsion provided in this application is also applicable to various other coupling reactions, such as the Suzuki-Miyaura reaction, the Buchwald-Hartwig reaction, the Heck reaction involving diazonium salts, the Sonogashira reaction, etc.

[0033] This application also provides an apparatus for a continuous column flow coupling reaction based on Pickering emulsion, wherein the apparatus is the aforementioned column reactor, as shown above. Figure 1 As shown, the column reactor includes a reactor body;

[0034] A filter plate, disposed inside the reactor body, is used to separate the oil-soluble product, Pickering emulsion, and carbonate aqueous solution; an oil-soluble product outlet and a carbonate aqueous solution inlet are disposed above the reactor body; and a carbonate aqueous solution outlet and an oil-soluble reactant inlet are disposed below the reactor body.

[0035] The technical solutions in the embodiments of this application will be clearly and completely described below in conjunction with the method of continuous coupling reaction of column flow based on Pickering emulsion. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments.

[0036] Example 1: Continuous Suzuki Coupling Reaction Based on Pickering Emulsion Column Flow

[0037] Add 50 mg of GO to 40 mL of deionized water, then add 160 mg of NaOH and sonicate for 30 min. Add 618 μL of N,N-diethylethylenediamine, sonicate again for 15 min, and then place in a water bath and stir at 70 °C for 2.5 h. After the reaction is complete, wash with pure water until neutral, and freeze-dry to obtain amine-modified GO, named GO-NDEE.

[0038] 35g of Pd[P(C6H5)3]4 was added to 8mL of toluene solution and mixed evenly by magnetic stirring. 9mg of GO-NDEE was dispersed in 4mL of aqueous solution by ultrasonication. Then the toluene solution and aqueous solution were mixed together and stirred at high speed of 8000rpm to form a Pickering emulsion of supported catalyst.

[0039] The Pickering emulsion of the prepared supported catalyst was transferred to a column reactor with an inner diameter of 2.0 cm, and the reactor temperature was set to 80 °C. A toluene solution of 0.125 mol / L bromobenzene and 0.15 mol / L phenylboronic acid was continuously introduced from the bottom of the column reactor at a flow rate of 2.5 mL / h using a peristaltic pump. A 0.25 mol / L potassium carbonate aqueous solution was continuously introduced from the top of the column reactor at a flow rate of 2.5 mL / h using a peristaltic pump to carry out the Suzuki coupling reaction. The reaction was carried out continuously for 1000 hours, and the conversion rate was always greater than 80%.

[0040] Example 2: Continuous Suzuki Coupling Reaction Based on Pickering Emulsion Column Flow

[0041] Place 5 mL of GO and 160 mg of NaOH in a 100 mL beaker, add 35 mL of deionized water, and stir for 10 minutes. Then, ultrasonically disperse the mixture in an ultrasonic cleaner for 30 minutes. Add 1.5 mL of NDEP, stir for 30 minutes, and then transfer to a 70°C water bath for reaction for 3 hours. After the reaction is complete, allow the mixture to cool to room temperature, wash with deionized water until the mixture is neutral, and obtain GO-NDEP. Freeze-dry and store for later use.

[0042] Add 100 mg GO-NDEP and 100 mL of water to a 250 mL beaker, and sonicate for 1.5 h to disperse GO-NDEP evenly in the water. Add 221 μL of Na2PdCl4 (50 mg / mL), stir for 15 min, then add 12.4 mg PVP, and after 50 min, slowly add 40 mL of NaBH4 solution (0.18 mg / mL), continue stirring for 30 min, then centrifuge with deionized water and freeze-dry to obtain Pd / GO-NDEP.

[0043] Take 12 mg of dried Pd / GO-NDEP and place it in a 50 mL glass bottle. Add 12 mL of deionized water and sonicate for 30 min to uniformly disperse Pd / GO-NDEP in the water. Add 24 mL of toluene to the dispersion and emulsify using a high-speed shear mixer while stirring at 10000 rpm for 2–5 min to obtain a Pickering emulsion with the supported catalyst.

[0044] The Pickering emulsion of the prepared supported catalyst was transferred to a column reactor with an inner diameter of 2.0 cm, and the reactor temperature was set to 80 °C. A toluene solution of 0.28 mol / L bromobenzene and 0.33 mol / L phenylboronic acid was continuously introduced from the bottom of the reactor at a flow rate of 3 mL / h using a peristaltic pump. A 0.56 mol / L cesium carbonate aqueous solution was continuously introduced from the top of the reactor at a flow rate of 3 mL / h using a peristaltic pump to carry out the Suzuki coupling reaction. The reaction was carried out continuously for 1000 h, and the conversion rate was always greater than 80%.

[0045] Example 3: Continuous Suzuki Coupling Reaction Based on Pickering Emulsion Column Flow

[0046] Take 10 mL of the prepared GO solution (10 mg / mL), add deionized water to make up to 100 mL, then add 0.16 g NaOH and stir for 15 min. Next, add 1.05 mL of hexylamine and stir for 0.5 h. Then, stir the mixture at 70 °C for 3 h. After the reaction is complete, wash the product with deionized water until neutral, freeze-dry, and grind for later use to obtain the primary amine-modified GO-based emulsifier, denoted as GO-HX.

[0047] 80 mg of GO-HX was ultrasonically dispersed in 170 mL of deionized water. Then, 0.3 mL of Na₂PdCl₄ solution (50 mg / mL) and 0.4 mL of Ni(NO₃)₂·6H₂O (30 mg / mL) were added, and the mixture was stirred for 35 min. Finally, 0.5 mL of NaBH₄ aqueous solution (50 mg / mL) was added, and the mixture was stirred for 40 min. The suspension was centrifuged, and the resulting product was washed 5–7 times with ethanol, then 3–5 times with deionized water. After vacuum freeze-drying, the product was ground for later use, yielding a bimetallic supported emulsion catalyst, denoted as NiPd / GO-HX.

[0048] Take 28 mg of the prepared NiPd / GO-HX solid powder and add it to a screw-type micro-volume bottle containing 4 mL of aqueous solution and 8 mL of toluene. After ultrasonic dispersion for 1 h, emulsify it at 10,000 rpm for 5 min using a high-speed shearing machine and let it stand for 0.5 h to obtain the Pickering emulsion of the supported catalyst, which is ready for use.

[0049] The Pickering emulsion of the prepared supported catalyst was transferred to a column reactor with an inner diameter of 2.0 cm, and the reactor temperature was set to 80 °C. A toluene solution of 0.15 mol / L iodobenzene and 0.25 mol / L phenylboronic acid was continuously introduced from the bottom of the reactor at a flow rate of 3.0 mL / h using a peristaltic pump. An aqueous solution of cesium carbonate was continuously introduced from the top of the reactor at a flow rate of 3.0 mL / h using a peristaltic pump to carry out the Suzuki coupling reaction. The reaction was carried out continuously for 1000 h, and the conversion rate was always greater than 80%.

[0050] Example 4: Continuous Heck Coupling Reaction Based on Pickering Emulsion Column Flow

[0051] 5 mL of GO and 160 mg of NaOH were placed in a 100 mL beaker, and 35 mL of deionized water was added. The mixture was then stirred for 10 minutes. The mixture was then ultrasonically dispersed in an ultrasonic cleaner for 30 minutes. 11 mg of GS (guanidinobutylamine sulfate) was added, and the mixture was stirred for 30 minutes before being transferred to an 80°C oil bath and reacted for 3 hours. After the reaction was complete, the mixture was allowed to cool to room temperature and then washed with deionized water until neutral to obtain GO-GS.

[0052] 40 mg of palladium chloride was dissolved in a mixture of 2 mL of water and 0.2 mL of concentrated hydrochloric acid. Then, 560 mg of GO-GS was added and the mixture was stirred. After the solution became clear, 15 mg of NaBH4 was added in portions over 25 minutes, for a total of 230 mg. The mixture was stirred for 30 minutes. The solid precipitate was washed with water (50 mL) and acetone (20 mL) and dried under vacuum to obtain a black, fine, lustrous powder, which was Pd / GO-GS.

[0053] Take 30 mg of the prepared Pd / GO-GS solid powder and add it to a screw-type micro-volume bottle containing 6 mL of aqueous solution and 12 mL of toluene. After ultrasonic dispersion for 1.5 h, emulsify it for 5 min at 10000 rpm using a high-speed shearing machine to obtain the Pickering emulsion with the supported catalyst.

[0054] The Pickering emulsion of the prepared supported catalyst was transferred to a column reactor with an inner diameter of 2.0 cm. The reactor temperature was 90 °C. A solution of 0.2 mol / L styrene and 0.5 mol / L iodobenzene in toluene was continuously introduced from the bottom of the reactor at a flow rate of 1.5 mL / h using a peristaltic pump. An aqueous solution of 0.6 mol / L triethylamine and 0.6 mol / L acetic acid was continuously introduced from the bottom of the reactor at a flow rate of 1.5 mL / h using a peristaltic pump to carry out the Heck coupling reaction. The reaction was carried out continuously for 1000 h, and the conversion rate was always greater than 80%.

[0055] Example 5: Continuous Sonogashira Coupling Reaction Based on Pickering Emulsion Column Flow

[0056] Add 50 mg of GO to 40 mL of deionized water, then add 160 mg of NaOH and sonicate for 30 min. Add 618 μl of N,N-diethylethylenediamine, sonicate again for 15 min, and then place in a water bath and stir at 70 °C for 2.5 h. After the reaction is complete, wash with pure water until neutral, and freeze-dry to obtain amine-modified GO, named GO-NDEE;

[0057] First, dissolve 0.23g of Pd(NO3)2 in 40mL of water, then add 0.25g of CuSO4. 4. 5H₂O was dissolved in 40 mL of water, and the two solutions were then mixed in a round-bottom flask and stirred for 30 min. 5 g of Tulsi leaves were then collected, thoroughly washed with distilled water, dried on absorbent paper, pulverized in a mortar, boiled in 50 mL of water for 5 min, centrifuged, and the filtrate was collected as the leaf extract. Then, 6 mL of the leaf extract was added to the above-mentioned Pd(NO₃)₂ and CuSO₄ mixture. 4. The mixture was placed in a solution of 5H₂O and allowed to stand for 5 minutes, then stirred at room temperature for one day. The resulting mixture was centrifuged and the nanoparticles were collected to obtain Pd / Cu nanoparticles.

[0058] The obtained Pd / Cu nanoparticles were dissolved in 100 mL of water, and then 4 g of GO-NDEE was added. The mixture was centrifuged, washed several times with water and acetone, and dried in air at room temperature to obtain Pd / Cu@GO-NDEE.

[0059] Take 5 mg of the prepared Pd / Cu@GO-NDEE and add it to a screw-type microvolume bottle containing 4 mL of aqueous solution and 8 mL of toluene. After ultrasonic dispersion for 1 h, emulsify it at 10,000 rpm for 2–5 min using a high-speed shear machine and let it stand for 0.5 h to obtain the Pickering emulsion of the supported catalyst, which is ready for use.

[0060] The Pickering emulsion of the prepared supported catalyst was transferred to a column reactor with an inner diameter of 2.0 cm, and the reaction temperature of the reactor was set to 80 °C. A toluene solution of 0.1 mol / L iodobenzene and 0.1 mol / L phenylacetylene was continuously introduced from the bottom of the reactor at a flow rate of 2.5 mL / h using a peristaltic pump. A 0.1 mol / L aqueous solution of K2CO3 was continuously introduced from the top of the reactor at a flow rate of 2.5 mL / h using a peristaltic pump to carry out the Sonogashira coupling reaction. The reaction was carried out continuously for 1000 h, and the conversion rate was always greater than 80%.

[0061] In summary, taking the Sukuki coupling reaction as an example, this application presents a novel method for continuous Suzuki coupling reactions using a column reactor. This method involves filling a column reactor with a catalyst-supported Pickering emulsion, and using a peristaltic pump to introduce oil-soluble reactants and carbonate aqueous solutions from the bottom and top of the reactor, respectively. This effectively solves the problems of high mass transfer resistance and low catalytic efficiency in Suzuki coupling reactions. Furthermore, using an oil-in-water Pickering emulsion as an example, this method utilizes the concentration difference between reactants and products in the dispersed and oil phases, eliminating the need for demulsification / emulsification to collect products. The operation is simple and easy to implement, the conditions are mild, it is applicable to most coupling reactions, and it is easy to scale up for production.

[0062] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of this patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

[0063] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A method of column flow continuous coupling reaction based on Pickering emulsion, characterized in that, The method comprises the following steps: The graphene oxide is subjected to wet activation treatment under the action of an activator in an alkaline condition to obtain graphene oxide with interface activity; The graphene oxide with interface activity is mixed with a catalyst in an organic solvent under high-speed stirring to obtain a Pickering emulsion of the catalyst supported on the graphene oxide; The Pickering emulsion of the catalyst supported on the graphene oxide is loaded into a column reactor, and an aryl halide and a boronic acid compound are continuously introduced from the lower part of the column reactor, and a carbonate is continuously introduced from the upper part of the column reactor to perform a coupling reaction; The step of mixing the graphene oxide with interface activity with the catalyst in the organic solvent under high-speed stirring to obtain the Pickering emulsion of the catalyst supported on the graphene oxide comprises the following steps: The graphene oxide with interface activity is ultrasonically dispersed in an aqueous solution, and a catalyst, polyvinylpyrrolidone and sodium borohydride are sequentially added and mixed, and then the mixture is subjected to drying treatment, ultrasonic dispersion treatment in deionized water, and addition of an organic solvent to obtain the Pickering emulsion of the catalyst supported on the graphene oxide under high-speed stirring; or the graphene oxide with interface activity is ultrasonically dispersed in an aqueous solution, and a mixed solution of the catalyst and the organic solvent is added to obtain the Pickering emulsion of the catalyst supported on the graphene oxide under high-speed stirring; the catalyst is a Pd-based catalyst; The coupling reaction is a Suzuki reaction; The column reactor comprises a reactor body and a filter plate arranged in the interior of the reactor body to separate an oil-soluble product, a Pickering emulsion and an aqueous carbonate solution; an oil-soluble product outlet and an aqueous carbonate solution inlet are arranged at the upper part of the reactor body; and an aqueous carbonate solution outlet and an oil-soluble reactant inlet are arranged at the lower part of the reactor body.

2. The method of Pickering emulsion-based column flow continuous coupling reaction according to claim 1, characterized in that, The step of subjecting the graphene oxide to activation treatment under the action of an activator in an alkaline condition to obtain graphene oxide with interface activity comprises the following steps: The graphene oxide is dispersed in deionized water, and a wetting activator is added under an alkaline condition and subjected to ultrasonic treatment, and then the mixture is subjected to water bath mixing treatment at 60-90 DEG C, and then washing and drying treatment to obtain graphene oxide with interface activity.

3. The method of Pickering emulsion-based column flow continuous coupling reaction according to claim 2, characterized in that, The wetting activator is one or more of N, N-diethylethylenediamine, N, N-diethyl-1, 3-propanediamine, guanidylbutylamine sulfate and hexylamine.

4. The Pickering emulsion-based column flow continuous coupling reaction method according to claim 1, wherein the aryl halide is one or more of bromobenzene, iodobenzene and chlorobenzene; and the boronic acid compound is one or more of phenylboronic acid, 2-methoxyphenylboronic acid, 2-methylphenylboronic acid, 4-methylphenylboronic acid and 4-methoxyiodobenzene.

5. The Pickering emulsion-based column flow continuous coupling reaction method according to claim 1, wherein the carbonate is one or more of Na2CO3, NaHCO3, K2CO3, KHCO3 and Li2CO3.

6. The method of Pickering emulsion-based column flow continuous coupling reaction according to claim 1, wherein the stirring speed is 5000-1000 rpm under the high speed stirring condition.

7. The method of Pickering emulsion-based column flow continuous coupling reaction according to claim 1, wherein the temperature of the column reactor is 60-90 ℃; and the flow rate of the column reactor is 2-10 mL / h.

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