Continuous reaction system and continuous method for producing 3',4',5'-trifluorobiphenyl-2-amine

Abstract

The present invention provides a continuous reaction system and a continuous method for producing 3',4',5'-trifluorobiphenyl-2-amine. The system includes: a first continuous module, a second continuous module and a third continuous module, the first continuous module is used to sequentially carry out continuous Grignard reaction, continuous substitution reaction and continuous acidification reaction of raw materials including magnesium, 3,4,5-trifluorobromobenzene solution, trimethyl borate solution and acidic solution to obtain a first product system; the second continuous module is used to carry out continuous coupling reaction of raw materials including mixture A, solvent A, o-nitrochlorobenzene solution and the first product system to obtain a second product system; the third continuous module is used to carry out continuous reduction reaction of raw materials including solvent B, hydrogen and the second product system to obtain a third product system containing 3',4',5'-trifluorobiphenyl-2-amine. The system has the advantages of high efficiency and low investment.

Description

Technical Field

[0001] The invention relates to the technical field of 3',4',5'-trifluorobiphenyl-2-amine preparation, and in particular to a continuous reaction system and a continuous method for producing 3',4',5'-trifluorobiphenyl-2-amine. Background Art

[0002] At present, fluopyrabamide is BASF's second largest fungicide (second only to pyraclostrobin) and is very popular in the global fungicide market. 3',4',5'-trifluorobiphenyl-2-amine is an important intermediate for the synthesis of fluopyrabamide. There are many process routes for the synthesis of 3',4',5'-trifluorobiphenyl-2-amine, but they have the following defects to varying degrees:

[0003] (1) The existing process uses acetanilide as a raw material, and boron tribromide is required in the process of synthesizing 2-acetamidophenylboric acid. However, boron tribromide is highly dangerous, and the cost of the raw material acetanilide is high, which is not suitable for large-scale production;

[0004] (2) Using batch reactors for reactions involves multiple material transfers and requires a lot of manual work;

[0005] (3) The large amount of solvent and catalyst used leads to high cost and produces a lot of three wastes;

[0006] Therefore, in order to solve the problems of low production efficiency and high preparation cost, large demand for solvents and catalysts, and large amount of three wastes in the production of 3',4',5'-trifluorobiphenyl-2-amine, it is urgent to develop a system and method for producing 3',4',5'-trifluorobiphenyl-2-amine. Summary of the invention

[0007] The main purpose of the present invention is to provide a continuous reaction system and a continuous method for producing 3',4',5'-trifluorobiphenyl-2-amine, so as to solve the problems of low production efficiency, high preparation cost, large demand for solvent and catalyst, and large amount of three wastes in the production of 3',4',5'-trifluorobiphenyl-2-amine in the prior art.

[0008] In order to achieve the above-mentioned object, according to one aspect of the present invention, a continuous reaction system for continuously producing 3',4',5'-trifluorobiphenyl-2-amine is provided. The continuous reaction system comprises: a first continuous module, a second continuous module and a third continuous module. The first continuous module comprises a first continuous reactor. The first continuous reactor comprises a first inlet and a first outlet. The first inlet is respectively connected to a first raw material source comprising a magnesium source, a 3,4,5-trifluorobromobenzene solution source, a trimethyl borate solution source and an acidic solution source. The first continuous reactor is used to sequentially and continuously Grignard reaction the first raw material comprising magnesium, 3,4,5-trifluorobromobenzene solution, trimethyl borate solution and acidic solution. The first continuous module comprises a second continuous reactor, the second continuous reactor comprises a second inlet and a second outlet, the second inlet is respectively connected to a mixture A source, a solvent A source, an o-nitrochlorobenzene solution source and the first outlet, and the second continuous reactor is used for continuously coupling the raw materials including the mixture A, the solvent A, the o-nitrochlorobenzene solution and the first product system to obtain a second product system containing 3',4',5'-trifluorobiphenyl-2-nitro; wherein the mixture A comprises a metal catalyst and an alkaline additive; the third continuous module comprises a third continuous reaction The third continuous reactor comprises a third inlet and a third outlet, the third inlet is respectively connected to a solvent B source, a hydrogen source and a second outlet, the third continuous reactor is used for continuously reducing the raw materials including solvent B, hydrogen and the second product system to obtain a third product system containing 3',4',5'-trifluorobiphenyl-2-amine; wherein the third continuous reactor is filled with a reduction catalyst; wherein the first continuous reactor further comprises: an oscillating stirring reactor, comprising an inlet of the stirring reactor and an outlet of the stirring reactor, the inlet of the stirring reactor is respectively connected to a magnesium source and a 3,4,5-trifluorobromobenzene solution source, the oscillating stirring reactor is used for reducing the raw materials including magnesium and 3,4,5-trifluorobromobenzene The raw material of the bromofluorobenzene solution is subjected to a Grignard reaction to obtain a first reaction system containing 3,4,5-trifluorophenylmagnesium bromide; the oscillating stirring reactor comprises: a columnar reactor, the columnar reactor comprises a reaction column and a jacket arranged outside the reaction column, the jacket is used to pass a temperature control medium to control the temperature of the reaction column; a 3,4,5-trifluorobromobenzene solution feed port is arranged at the lower part of the reaction column, a magnesium feed port and a first reaction system outlet are arranged at the upper part of the reaction column; the 3,4,5-trifluorobromobenzene solution enters the columnar reactor through the 3,4,5-trifluorobromobenzene solution feed port, and magnesium enters the columnar reactor through the magnesium feed port; an oscillation source, the oscillation source is connected to the bottom end of the reaction column;A stirrer, one end of which is fixed to the top of the columnar reactor, and the other end of which extends inside the columnar reactor along the axial direction of the columnar reactor. A stirring motor is arranged on the top of the stirrer, and the stirring motor drives the M layers of stirring paddles vertically distributed in the columnar reactor to rotate through the stirring shaft, so as to mix the raw materials including magnesium and 3,4,5-trifluorobromobenzene solution in the columnar reactor, wherein M≥1. ;

[0009] Furthermore, the oscillating stirred reactor also includes an overflow baffle and an overflow pipe; the overflow pipe is connected to the oscillating stirred reactor and extends outside the oscillating stirred reactor, and the overflow pipe extends out of the oscillating stirred reactor by a length of 50 to 150 mm; the overflow baffle has a certain curvature, and the overflow baffle cover is arranged at a position outside the interface between the overflow pipe and the oscillating stirred reactor, wherein the edge of the end of the overflow baffle away from the inlet of the stirring reactor and opposite to the inlet of the stirring reactor is kept suspended from the inner wall of the oscillating stirred reactor, and the remaining edges of the overflow baffle are fixedly arranged on the inner wall of the oscillating stirred reactor; and / or, the projected area of ​​the overflow baffle on the inner wall of the oscillating stirred reactor where it is located is greater than the cross-sectional area of ​​the pipe mouth of the overflow pipe; and / or, the maximum radial distance between the overflow baffle and the inner wall where it is located is 20 to 50 mm; and / or, the overflow baffle is close to the inner wall of the oscillating stirred reactor. The angle between the extension direction of the end opposite to the inlet of the stirred reactor and the inner wall of the oscillating stirred reactor where the overflow pipe is located is 30~60°; and / or, the overflow baffle is made of stainless steel and / or polytetrafluoroethylene; the stirring shaft is vertically fixed to the center of the columnar reactor through the support bearing of the columnar reactor; and / or, the columnar reactor is made of 316L stainless steel and / or glass; the number of 3,4,5-trifluorobromobenzene solution feed ports and magnesium feed ports is independently 1~3; and / or, along the axial direction of the columnar reactor, the outer wall of the columnar reactor is sequentially surrounded by an upper heating jacket and a lower heating jacket, the temperature of the upper heating jacket is lower than that of the lower heating jacket, the upper heating jacket adopts an oil bath temperature control with a high and low temperature integrated machine, and the lower heating jacket adopts circulating hot water for temperature control.

[0010] Furthermore, a first continuous concentration device, a first continuous recrystallization device and a first continuous filtration device are sequentially arranged on the connecting pipeline between the first continuous module and the second continuous module, which are used to sequentially perform a first concentration treatment, a first recrystallization treatment and a first filtration treatment on the first product system to obtain 3,4,5-trifluorophenylboric acid; and / or, a substitution reaction device and an acidification reaction device are sequentially arranged on the connecting pipeline between the first continuous module and the second continuous module; the substitution reaction device is used to perform a continuous substitution reaction on the raw materials including the trimethyl borate solution and the first reaction system to obtain a second reaction system containing 3,4,5-trifluorophenylboric acid; the acidification reaction device is used to perform a continuous substitution reaction on the raw materials including the trimethyl borate solution and the first reaction system to obtain a second reaction system containing 3,4,5-trifluorophenylboric acid; The acidic solution and the raw materials of the second reaction system are continuously acidified to obtain the first product system; and / or the substitution reaction device and the acidification reaction device are independently selected from any one or more of a dynamic tubular reactor, a fully mixed flow reactor and a plug flow reactor; and / or the oscillating stirring reactor is a dynamic tubular reactor and / or a fully mixed flow reactor; and / or the first continuous concentration device is selected from any one or more of a falling film evaporator, a thin film evaporator and a flash tank; and / or the first continuous recrystallization device is selected from any one or more of a dynamic reaction kettle, a dynamic tubular reactor and a plug flow reactor; and / or the first continuous filtration device is a horizontal screw centrifuge and / or a turntable filter.

[0011] Furthermore, a first continuous dosing device, a second continuous filtration device, a second continuous concentration device, a second continuous recrystallization device and a third continuous filtration device are sequentially arranged on the connecting pipeline between the second continuous module and the third continuous module, which are used to sequentially perform a first dosing treatment, a second filtration treatment, a second concentration treatment, a second recrystallization treatment and a third filtration treatment on the second product system to obtain 3',4',5'-trifluorobiphenyl-2-nitro; and / or, the second continuous reactor is a dynamic tubular reactor and / or a fully mixed flow reactor; and / or, the second continuous concentration device is selected from any one or more of a falling film evaporator, a thin film evaporator and a flash tank; and / or, the second continuous recrystallization device is selected from any one or more of a dynamic reactor, a dynamic tubular reactor and a plug flow reactor; and / or, the second continuous filtration device and the third continuous filtration device are each independently a horizontal screw centrifuge and / or a turntable filter; and / or, the first continuous dosing device is a dynamic tubular reactor and / or a fully mixed flow reactor.

[0012] Furthermore, the third continuous module also includes a drying device; a second continuous batching device and a third continuous concentrating device are sequentially arranged on the connecting pipeline between the third continuous module and the drying device; the second continuous batching device is used to perform a second batching treatment on the raw material including 3',4',5'-trifluorobiphenyl-2-nitro and solvent B to obtain a second batching; the third continuous concentrating device is used to perform a third concentration treatment on the third product system to obtain a third concentrated product; the drying device is used to dry the third concentrated product to obtain 3',4',5'-trifluorobiphenyl-2-amine; and / or, the third continuous reactor is selected from any one or more of an axial adiabatic fixed bed reactor, a radial adiabatic fixed bed reactor and a shell and tube fixed bed reactor; and / or, the third continuous concentrating device is selected from any one or more of a falling film evaporator, a thin film evaporator and a flash tank; and / or, the second continuous batching device is an automatic dynamic tubular reactor and / or a fully mixed flow reactor.

[0013] Furthermore, the material of the stirring paddle is stainless steel and / or polytetrafluoroethylene, and the shape of the stirring paddle is selected from any one or more of propulsion type, turbine type and spiral type; the stirring blades of the stirring paddle are detachable or non-detachable and are installed on the hub of the stirring shaft arranged in the axial direction or welded on the stirring shaft.

[0014] According to another aspect of the present invention, there is provided a continuous method for preparing 3',4',5'-trifluorobiphenyl-2-amine using the above-mentioned continuous reaction system, the continuous method comprising: step S1, subjecting a first raw material comprising metal magnesium, 3,4,5-trifluorobromobenzene solution, trimethyl borate solution and acidic solution to Grignard reaction, substitution reaction and acidification reaction in sequence to obtain a first product system containing 3,4,5-trifluorophenylboric acid; step S2, subjecting a second raw material comprising 3,4,5-trifluorophenylboric acid, a metal catalyst, an alkaline additive, a solvent A and an o-nitrochlorobenzene solution to a coupling reaction to obtain a second product system containing 3',4',5'-trifluorobiphenyl-2-nitro; step S3, subjecting a third raw material comprising 3',4',5'-trifluorobiphenyl-2-nitro, hydrogen, a solvent B and a reduction catalyst to a reduction reaction to obtain a third product system containing 3',4',5'-trifluorobiphenyl-2-amine.

[0015] Furthermore, the above step S1 also includes: step S11, subjecting the raw materials including metallic magnesium and 3,4,5-trifluorobromobenzene solution to a Grignard reaction to obtain a first reaction system containing 3,4,5-trifluorophenylmagnesium bromide; step S12, subjecting the raw materials including the first reaction system and trimethyl borate solution to a substitution reaction to obtain a second reaction system; step S13, subjecting the raw materials including the second reaction system and an acidic solution to an acidification reaction to obtain a first product system; step S14, subjecting the first product system to a first concentration treatment, a first recrystallization treatment and a first filtration treatment in sequence to obtain 3,4,5-trifluorophenylboric acid; wherein, The solvents in the 3,4,5-trifluorobromobenzene solution and the trimethyl borate solution are independently selected from any one or more of tetrahydrofuran, ether and toluene; the feed rate of the 3,4,5-trifluorobromobenzene solution is 100-150 g / min, the metal magnesium is magnesium powder, the feed rate of the metal magnesium is 1-3 g / min, the reaction temperature of the Grignard reaction is 30-65° C.; the reaction time of the Grignard reaction is 30-90 min; and / or, the feed rate of the first reaction system is 101-153 g / min, the feed rate of the trimethyl borate solution is 50-150 g / min; the reaction temperature of the substitution reaction is -40- 0℃; the reaction time of the substitution reaction is 10~60min; and / or, the feed rate of the second reaction system is 200~350g / min; the feed rate of the acidic solution is 100~250g / min; the acidic solution is selected from any one or more of hydrochloric acid solution, sulfuric acid solution and acetic acid solution; the mass concentration of the acidic solution is 5~20%; the reaction temperature of the acidification reaction is 0~20℃; the reaction time of the acidification reaction is 10~60min; and / or, the feed rate of the first product system is 300~500g / min; the temperature of the first continuous concentration treatment is 40~60℃; the first continuous concentration treatment The pressure is -0.06~-0.1MPa; the feed rate of the raw material in the first recrystallization treatment is 40~150g / min; the first recrystallization solvent in the first recrystallization treatment is selected from any one or more of n-heptane, n-hexane and dichloromethane; the mass ratio of the raw material to the first recrystallization solvent in the first recrystallization treatment is 0.42~1.25:1g / min; the temperature of the first recrystallization treatment is 0~40℃; the time of the first recrystallization treatment is 30~60min; and / or, the feed rate of the raw material in the first filtration treatment is 100~2000g / min; the temperature of the first filtration treatment is 0~40℃.

[0016] Furthermore, the above step S2 also includes: step S21, performing a first batching treatment on a raw material including 3,4,5-trifluorophenylboric acid and solvent A to obtain a first batching; step S22, performing a coupling reaction on a second raw material including the first batching, a metal catalyst, an alkaline additive and an o-nitrobromobenzene solution to obtain a second product system; step S23, sequentially performing a second filtration treatment, a second concentration treatment, a second recrystallization treatment and a third filtration treatment on the second product system to obtain 3',4',5'-trifluorobiphenyl-2-nitro; wherein 3,4,5-trifluorophenylboric acid is a solid, and the feed rate of 3,4,5-trifluorophenylboric acid is 10~25g / min; the solvent Agent A is selected from any one or more of 1,4-dioxane, toluene and xylene, the mass ratio of 3,4,5-trifluorophenylboric acid to solvent A is 0.2-0.33:1; the temperature of the first ingredient treatment is 20-40°C; the time of the first ingredient treatment is 10-30min; and / or, the feed rate of the first ingredient is 50-100g / mL; the feed rate of the o-nitrobromobenzene solution is 40-100g / min; the solvent in the o-nitrobromobenzene solution is selected from one or more of 1,4-dioxane, toluene and xylene; the mass concentration of the o-nitrobromobenzene solution is 16-31%, and the total feed rate of the metal catalyst and the alkaline additive is 10-30g / min n; the metal catalyst is selected from any one or more of Pd(dppf)Cl2, Pd(dba) and Pd(PPh3)4; the alkaline additive is selected from any one or more of potassium phosphate, potassium carbonate and cesium carbonate; the mass ratio of the metal catalyst to the alkaline additive is 1:2~5; the atmosphere of the coupling reaction is nitrogen and / or argon; the reaction temperature of the coupling reaction is 80~120℃; the reaction time of the coupling reaction is 60~180min; and / or, the feed rate of the second product system is 40~140g / min; the temperature of the second filtration treatment is 0~40℃; and / or, the feed rate of the raw material in the second concentration treatment is 130~170g / min ; The temperature of the second concentration treatment is 40~60℃; The pressure of the second concentration treatment is -0.06~0.1MPa; and / or, the feed rate of the raw material in the second recrystallization treatment is 10~30g / min; The second recrystallization solvent in the second recrystallization treatment is selected from any one or more of isopropanol, ethanol and isobutanol; The mass ratio of the raw material to the second recrystallization solvent in the second recrystallization treatment is 0.62~0.8:1; The temperature of the second recrystallization treatment is -10~20℃; The time of the second recrystallization treatment is 30~60min; and / or, the feed rate of the raw material in the third filtration treatment is 10~20g / min; The temperature of the third filtration treatment is 0~20℃.

[0017] Furthermore, the above step S3 also includes: step S31, subjecting the raw material including 3',4',5'-trifluorobiphenyl-2-nitro and solvent B to a second batching treatment to obtain a second batching; step S32, subjecting the third raw material including the second batching and hydrogen to a reduction reaction with a reduction catalyst to obtain a third product system; step S33, subjecting the third product system to a third concentration treatment and a drying treatment in sequence to obtain 3',4',5'-trifluorobiphenyl-2-amine; wherein the feed rate of 3',4',5'-trifluorobiphenyl-2-nitro is 10-15 g / min; solvent B is selected from any one or more of methanol, ethanol and ethyl acetate, and the mass ratio of 3',4',5'-trifluorobiphenyl-2-nitro to solvent B is 0.2-0.56:1; the temperature of the second batching treatment is 2 0~40℃; the time for the second ingredient treatment is 10~30min; and / or, the feed rate of the second ingredient is 15~40g / min; the reduction catalyst is selected from any one or more of aluminum-nickel alloy powder, zinc-nickel alloy powder and zinc-aluminum alloy powder; the mass ratio of the two alloy elements in the reduction catalyst is 1:0.95~1.05; the pressure of the reduction reaction is 0.8~1.5MPa; the reaction temperature of the reduction reaction is 60~90℃; the reaction time of the reduction reaction is 60~180min; and / or, the feed rate of the third product system is 15~40g / min; the temperature of the third concentration treatment is 40~60℃; the pressure of the third concentration treatment is -0.06~-0.1MPa; and / or, the temperature of the drying treatment is 40~60℃, and the time of the drying treatment is 30~90min.

[0018] By applying the technical solution of the present invention, the present invention provides a continuous reaction system for the continuous production of 3',4',5'-trifluorobiphenyl-2-amine with high efficiency and low investment, wherein the oscillating stirring reactor can provide a favorable reaction environment for liquid-solid or gas-liquid-solid multiphase flow reactions, and can be used not only for homogeneous reactions but also for multiphase reactions, especially for liquid-solid reactions involving solid raw materials with large specific gravity, which have excellent performance that cannot be replaced by traditional stirring reactors. The oscillating stirring reactor includes a columnar reactor, an oscillation source and an agitator, which can achieve that the solids accumulated at the bottom of the reactor can be reciprocated and contacted with the upper materials again to fully react, so that the axial liquid-solid ratio in the entire reaction chamber is balanced, the reaction efficiency is improved, and at the same time, magnesium can be prevented from being deposited at the bottom of the columnar reactor, resulting in the inability to reciprocate and mix the deposited magnesium by stirring alone during long-term operation, which leads to insufficient raw material reaction and low product yield. In addition, the oscillating stirring reactor of the present invention is a process intensification device with a compact geometric structure, axial periodic oscillation conditions and radial sufficient stirring. When the oscillating stirring reactor is working, the oscillation source is located at the bottom of the reactor, and the generated pulse oscillation is superimposed on the average flow rate to drive the solid materials such as the bottom powder in the reactor to reciprocate up and down, thereby forming an irregular shear rate distribution in the reactor cavity. At the same time, the agitator rotates so that the material in the reactor rotates around the axis with the stirring paddle of the stirring device, so that the central liquid level partially drops, and the free surface forms a parabola to form a vortex, thereby allowing the material to fully react. In summary, the oscillating stirring reactor of the present application can achieve efficient mixing of the raw material 3,4,5-trifluorobromobenzene solution and metallic magnesium, has the advantages of shortening the reaction time, and the first reaction system (Grignard reagent) containing 3,4,5-trifluorophenyl magnesium bromide has a high concentration, and can effectively solve the initiation and heat dissipation problems of the Grignard reaction, and effectively avoid the safety hazards such as the impact of the material caused by the drastic temperature rise of the Grignard reaction. In addition, the third continuous reactor can reduce the amount of solvent and reduction catalyst used in the reduction reaction process and post-treatment process, thereby reducing the amount of three wastes generated. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The drawings constituting a part of the present application are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0020] Figure 1 A schematic diagram of a continuous reaction system for continuously producing 3',4',5'-trifluorobiphenyl-2-amine according to the present application is shown;

[0021] Figure 2 A schematic diagram of an oscillating stirred reactor of the present application is shown.

[0022] Among them, the above drawings include the following reference numerals:

[0023] 1. First continuous reactor; 2. Second continuous reactor; 3. Third continuous reactor; 4. First continuous concentration device; 5. First continuous recrystallization device; 6. First continuous filtration device; 7. First continuous batching device; 8. Second continuous filtration device; 9. Second continuous concentration device; 10. Second continuous recrystallization device; 11. Third continuous filtration device; 12. Drying device; 13. Second continuous batching device; 14. Third continuous concentration device; 20. First continuous module; 30. Second continuous module; 40. Third continuous module; 101. Oscillating stirring reactor; 102. Substitution reaction device; 103. Acidification reaction device; 01. Column reactor; 02. Oscillation source; 03. Agitator; 04. Overflow baffle; 05. Overflow pipe; 011. Reaction column; 012. Jacket; 013. Agitator. DETAILED DESCRIPTION

[0024] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0025] As analyzed in the background technology of the present application, the prior art has problems in the production of 3',4',5'-trifluorobiphenyl-2-amine, such as low production efficiency and high preparation cost, large demand for solvent and catalyst usage, and large amount of three wastes. In order to solve the above problems, the present application provides a continuous reaction system and a continuous method for producing 3',4',5'-trifluorobiphenyl-2-amine.

[0026] In a typical embodiment of the present application, a continuous reaction system for continuously producing 3',4',5'-trifluorobiphenyl-2-amine is provided, such as Figure 1As shown, the continuous reaction system comprises: a first continuous module 20, a second continuous module 30, and a third continuous module 40, wherein the first continuous module 20 comprises a first continuous reactor 1, wherein the first continuous reactor 1 comprises a first inlet and a first outlet, wherein the first inlet is respectively connected to a first raw material source comprising a magnesium source, a 3,4,5-trifluorobromobenzene solution source, a trimethyl borate solution source, and an acidic solution source, and the first continuous reactor 1 is used to sequentially perform a continuous Grignard reaction, a continuous substitution reaction, and a continuous acidification reaction on the first raw material comprising magnesium, a 3,4,5-trifluorobromobenzene solution, a trimethyl borate solution, and an acidic solution to obtain a first product system containing 3,4,5-trifluorophenylboric acid; and the second continuous module 3 0 includes a second continuous reactor 2, the second continuous reactor 2 includes a second inlet and a second outlet, the second inlet is respectively connected to a mixture A source, a solvent A source, an o-nitrochlorobenzene solution source and the first outlet, the second continuous reactor 2 is used to continuously couple the raw materials including the mixture A, the solvent A, the o-nitrochlorobenzene solution and the first product system to obtain a second product system containing 3',4',5'-trifluorobiphenyl-2-nitro; wherein the mixture A includes a metal catalyst and an alkaline additive; the third continuous module 40 includes a third continuous reactor 3, the third continuous reactor 3 includes a third inlet and a third outlet, the third inlet is respectively connected to a solvent B source, a hydrogen source and the second outlet The third continuous reactor 3 is connected, and the third continuous reactor 3 is used to continuously reduce the raw materials including solvent B, hydrogen and the second product system to obtain a third product system containing 3',4',5'-trifluorobiphenyl-2-amine; wherein the third continuous reactor 3 is filled with a reduction catalyst; wherein the first continuous reactor 1 also includes: an oscillating stirring reactor 101, including a stirring reactor inlet and a stirring reactor outlet, the stirring reactor inlet is respectively connected to a magnesium source and a 3,4,5-trifluorobromobenzene solution source, and the oscillating stirring reactor 101 is used to carry out a Grignard reaction on the raw materials including magnesium and 3,4,5-trifluorobromobenzene solution to obtain a first reaction system containing 3,4,5-trifluorophenylmagnesium bromide; The stirring reactor 101 comprises: a column reactor 01, an oscillation source 02, and an agitator 03. The column reactor 01 comprises a reaction column 011 and a jacket 012 arranged outside the reaction column 011, and the jacket 012 is used to pass a temperature control medium to control the temperature of the reaction column 011; a 3,4,5-trifluorobromobenzene solution feed port is arranged at the lower part of the reaction column 011, and a magnesium feed port and a first reaction system outlet are arranged at the upper part of the reaction column 011; the 3,4,5-trifluorobromobenzene solution enters the column reactor 01 through the 3,4,5-trifluorobromobenzene solution feed port, and magnesium enters the column reactor 01 through the magnesium feed port; the oscillation source 02 is connected to the bottom end of the reaction column 011;A stirring motor is arranged on the top of the stirrer 03, and the stirring motor drives the M layers of stirring paddles 013 vertically distributed in the columnar reactor 01 to rotate through the stirring shaft, so as to mix the raw materials including magnesium and 3,4,5-trifluorobromobenzene solution in the columnar reactor 01, wherein M≥1. ;

[0027] The present invention provides a high-efficiency, low-investment continuous reaction system for the continuous production of 3',4',5'-trifluorobiphenyl-2-amine, wherein the oscillating stirring reactor 101 can provide a favorable reaction environment for liquid-solid or gas-liquid-solid multiphase flow reactions, and can be used not only for homogeneous reactions, but also for multiphase reactions, especially for liquid-solid reactions involving solid raw materials with a large specific gravity, which have excellent performance that cannot be replaced by traditional stirring reactors. The oscillating stirring reactor 101 includes a columnar reactor 01, an oscillation source 02, and an agitator 03, which can achieve that the solids accumulated at the bottom of the reactor can be reciprocated and contacted with the upper materials again to fully react, so that the axial liquid-solid ratio in the entire reaction chamber is balanced, the reaction efficiency is improved, and at the same time, magnesium can be prevented from being deposited at the bottom of the columnar reactor, resulting in the inability to reciprocate and mix the deposited magnesium by stirring alone during long-term operation, thereby resulting in insufficient raw material reaction and low product yield. In addition, the oscillating stirring reactor 101 of the present invention is a process intensification device with a compact geometric structure, axial periodic oscillation conditions, and radial sufficient stirring. When the oscillating stirring reactor 101 is working, the oscillation source 02 is located at the bottom of the reactor, and the generated pulse oscillation is superimposed on the average flow rate to drive the solid materials such as the bottom powder in the reactor to reciprocate up and down, thereby forming an irregular shear rate distribution in the reactor cavity. At the same time, the agitator 03 rotates to make the material in the reactor rotate around the axis with the stirring paddle of the stirring device, so that the central liquid level partially drops, and the free surface forms a parabola to form a vortex, thereby allowing the material to fully react. In summary, the oscillating stirring reactor 101 of the present application can achieve efficient mixing of the raw material 3,4,5-trifluorobromobenzene solution and metallic magnesium, has the advantages of shortening the reaction time, and the first reaction system (Grignard reagent) containing 3,4,5-trifluorophenyl magnesium bromide has a high concentration, and can effectively solve the initiation and heat dissipation problems of the Grignard reaction, and effectively avoid the safety hazards such as the impact of the material caused by the drastic temperature rise of the Grignard reaction. The third continuous reactor 3 can reduce the amount of solvent and reduction catalyst used in the reduction reaction process and post-treatment process, thereby reducing the amount of three wastes generated.

[0028] In one embodiment of the present application, the oscillating stirred reactor 101 further includes an overflow baffle 04 and an overflow pipe 05; the overflow pipe 05 is connected to the oscillating stirred reactor 101 and extends outside the oscillating stirred reactor 101, and the overflow pipe 05 extends outside the oscillating stirred reactor 101 by a length of 50 to 150 mm; the overflow baffle 04 has a certain curvature, and the overflow baffle 04 is covered at a position outside the interface between the overflow pipe 05 and the oscillating stirred reactor 101, wherein the edge of one end of the overflow baffle 04 away from the inlet of the stirring reactor and opposite to the inlet of the stirring reactor is kept suspended from the inner wall of the oscillating stirred reactor 101, and the remaining edges of the overflow baffle 04 are fixedly arranged on the inner wall of the oscillating stirred reactor 101; and / or, the projected area of ​​the overflow baffle 04 on the inner wall of the oscillating stirred reactor 101 where it is located is greater than the cross-sectional area of ​​the pipe mouth of the overflow pipe 05; and / or, the maximum radial distance between the overflow baffle 04 and the inner wall where it is located is 20~50mm; and / or, the angle between the extension direction of the end of the overflow baffle 04 close to the inlet of the stirred reactor and opposite to the inlet of the stirred reactor and the inner wall of the oscillating stirred reactor 101 where the overflow pipe 05 is located is 30~60°; and / or, the material of the overflow baffle 04 is stainless steel and / or polytetrafluoroethylene; the stirring shaft is vertically fixed to the center of the columnar reactor 01 through the support bearing of the columnar reactor 01; and / or, the material of the columnar reactor 01 is 316L stainless steel and / or glass; the number of 3,4,5-trifluorobromobenzene solution feed inlet and magnesium feed inlet is independently 1~3; and / or, along the axial direction of the columnar reactor 01, the outer wall of the columnar reactor 01 is sequentially surrounded by an upper heating jacket and a lower heating jacket, the temperature of the upper heating jacket is lower than the temperature of the lower heating jacket, the upper heating jacket adopts a high and low temperature integrated machine for oil bath temperature control, and the lower heating jacket adopts circulating hot water for temperature control.

[0029] The overflow baffle 04 provided on the inner wall is helpful to change the flow pattern of fluid movement, thereby changing the flow pattern, velocity magnitude and direction of the material in the reactor, so that the solid particle material is evenly suspended in the liquid, and the accumulation of solid particles in the local space in the reactor is prevented as much as possible, thereby helping to further control the flow pattern and strengthen the stirring effect. It is preferred to control the material of the overflow baffle 04, the length of the overflow pipe 05 extending outside the oscillating stirring reactor 101, the maximum radial distance between the overflow baffle 04 and the inner wall where it is located, and the angle between the extension direction of the end of the overflow baffle 04 close to the inlet of the stirring reactor and opposite to the inlet of the stirring reactor and the inner wall of the oscillating stirring reactor 101 where the overflow pipe 05 is located within the above range, which helps to flexibly adjust the overflow baffle 04 according to the equipment capacity, thereby ensuring that the flow rate of the outlet of the first reaction system is met while preventing magnesium from being lost from the pipe mouth of the overflow pipe 05, and at the same time, by optimizing the angle between the overflow pipe 05 and the cylinder of the oscillating stirring reactor 101, it can also play a certain role in preventing the outflowing magnesium from accumulating for a long time and blocking the overflow pipe mouth. Along the axial direction of the columnar reactor 01, an upper heating jacket and a lower heating jacket are sequentially arranged on the outer wall of the columnar reactor 01. It is preferred to control the temperature of the two respectively by using the above-mentioned heating method, and control the temperature of the upper heating jacket to be lower than the temperature of the lower heating jacket, which is helpful to use high temperature to induce the Grignard reagent reaction in the lower half of the reactor. After the material reaches the upper half, the external temperature is reduced to avoid the temperature surge phenomenon caused by the heat release of the Grignard reagent, thereby better controlling the overall temperature in the reaction system to be consistent.

[0030] In one embodiment of the present application, a first continuous concentration device 4, a first continuous recrystallization device 5 and a first continuous filtration device 6 are sequentially arranged on the connecting pipeline between the first continuous module 20 and the second continuous module 30, which are used to sequentially perform a first concentration treatment, a first recrystallization treatment and a first filtration treatment on the first product system to obtain 3,4,5-trifluorophenylboric acid; and / or, a substitution reaction device 102 and an acidification reaction device 103 are sequentially arranged on the connecting pipeline between the first continuous module 20 and the second continuous module 30; the substitution reaction device 102 is used to perform a continuous substitution reaction on the raw materials including the trimethyl borate solution and the first reaction system to obtain a second reaction system containing 3,4,5-trifluorophenylboric acid; the acidification reaction device 103 is used for continuously acidifying the raw materials including the acidic solution and the second reaction system to obtain the first product system; and / or, the substitution reaction device 102 and the acidification reaction device 103 are each independently selected from any one or more of a dynamic tubular reactor, a fully mixed flow reactor and a plug flow reactor; and / or, the oscillating stirring reactor 101 is a dynamic tubular reactor and / or a fully mixed flow reactor; and / or, the first continuous concentration device 4 is selected from any one or more of a falling film evaporator, a thin film evaporator and a flash tank; and / or, the first continuous recrystallization device 5 is selected from any one or more of a dynamic reaction kettle, a dynamic tubular reactor, and a plug flow reactor; and / or, the first continuous filtration device 6 is a horizontal screw centrifuge and / or a turntable filter.

[0031] The above-mentioned substitution reaction device 102 and acidification reaction device 103 are preferably used, which is conducive to carrying out substitution reaction and acidification reaction in sequence, so as to obtain the first product system; the above-mentioned first continuous concentration device 4, first continuous recrystallization device 5 and first continuous filtration device 6 are preferably used, which is conducive to carrying out the first concentration treatment, the first recrystallization treatment and the first filtration treatment on the first product system in sequence, so as to obtain and improve the quality of 3,4,5-trifluorophenylboric acid, which is further conducive to subsequent reactions.

[0032] In order to obtain and improve the purity of 3',4',5'-trifluorobiphenyl-2-nitro, in one embodiment of the present application, a first continuous batching device 7, a second continuous filtering device 8, a second continuous concentration device 9, a second continuous recrystallization device 10 and a third continuous filtering device 11 are sequentially arranged on the connecting pipeline between the second continuous module 30 and the third continuous module 40, which are used to sequentially perform the first batching treatment, the second filtering treatment, the second concentration treatment, the second recrystallization treatment and the third filtering treatment on the second product system to obtain 3',4',5'-trifluorobiphenyl-2-nitro nitro; and / or, the second continuous reactor 2 is a dynamic tubular reactor and / or a fully mixed flow reactor; and / or, the second continuous concentration device 9 is selected from any one or more of a falling film evaporator, a thin film evaporator and a flash tank; and / or, the second continuous recrystallization device 10 is selected from any one or more of a dynamic reactor, a dynamic tubular reactor, and a plug flow reactor; and / or, the second continuous filtration device 8 and the third continuous filtration device 11 are each independently a horizontal screw centrifuge and / or a turntable filter; and / or, the first continuous batching device 7 is a dynamic tubular reactor and / or a fully mixed flow reactor.

[0033] In one embodiment of the present application, the third continuous module 40 also includes a drying device 12; a second continuous batching device 13 and a third continuous concentrating device 14 are sequentially arranged on the connecting pipeline between the third continuous module 40 and the drying device 12; the second continuous batching device 13 is used to perform a second batching treatment on the raw material including 3',4',5'-trifluorobiphenyl-2-nitro and solvent B to obtain a second batching; the third continuous concentrating device 14 is used to perform a third concentration treatment on the third product system to obtain a third concentrated product; the drying device 12 is used to dry the third concentrated product to obtain 3',4',5'-trifluorobiphenyl-2-amine; and / or, the third continuous reactor 3 is selected from any one or more of an axial adiabatic fixed bed reactor, a radial adiabatic fixed bed reactor and a tube-in-tube fixed bed reactor; and / or, the third continuous concentrating device 14 is selected from any one or more of a falling film evaporator, a thin film evaporator and a flash tank; and / or, the second continuous batching device 13 is an automatic dynamic tubular reactor and / or a fully mixed flow reactor.

[0034] The second batching process is performed by the second continuous batching device 13, which helps to fully mix the raw materials including 3',4',5'-trifluorobiphenyl-2-nitro and solvent B in advance, thereby facilitating the subsequent reduction reaction. Preferably, the third product system is sequentially subjected to the third concentration process and the drying process by the second continuous batching device 13 and the third continuous concentration device 14, which helps to improve the yield and quality of 3',4',5'-trifluorobiphenyl-2-amine.

[0035] In one embodiment of the present application, the material of the stirring paddle 013 is stainless steel and / or polytetrafluoroethylene material, and the shape of the stirring paddle 013 is selected from any one or more of propulsion type, turbine type and spiral type; the stirring blades of the stirring paddle 013 are detachable or non-detachable and are installed on the hub of the stirring shaft arranged in the axial direction or welded on the stirring shaft.

[0036] The material, shape and installation method of the stirring blade 013 are preferably within the above range, which helps to flexibly adjust according to the properties of the raw materials, thereby increasing the residence time of the solid particles and increasing the contact area between the two phases, thereby improving the reaction efficiency of the Grignard reaction.

[0037] In another typical embodiment of the present application, a continuous method for preparing 3',4',5'-trifluorobiphenyl-2-amine using the above-mentioned continuous reaction system is provided, and the continuous method comprises: step S1, subjecting a first raw material comprising metallic magnesium, 3,4,5-trifluorobromobenzene solution, trimethyl borate solution and acidic solution to Grignard reaction, substitution reaction and acidification reaction in sequence to obtain a first product system containing 3,4,5-trifluorophenylboric acid; step S2, subjecting a second raw material comprising 3,4,5-trifluorophenylboric acid, a metal catalyst, an alkaline additive, a solvent A and an o-nitrochlorobenzene solution to a coupling reaction to obtain a second product system containing 3',4',5'-trifluorobiphenyl-2-nitro; step S3, subjecting a third raw material comprising 3',4',5'-trifluorobiphenyl-2-nitro, hydrogen, a solvent B and a reduction catalyst to a reduction reaction to obtain a third product system containing 3',4',5'-trifluorobiphenyl-2-amine.

[0038] The continuous method for preparing 3',4',5'-trifluorobiphenyl-2-amine in the present application is not only simple in reaction process, low in cost, and high in product yield. The above-mentioned first raw material is subjected to Grignard reaction, substitution reaction and acidification reaction in sequence, and 3,4,5-trifluorophenylboric acid can be obtained, so as to be conducive to 3,4,5-trifluorophenylboric acid in step S2 under the joint action of metal catalyst and alkaline additive, and it is easy to produce coupling reaction with o-nitrochlorobenzene solution to generate 3',4',5'-trifluorobiphenyl-2-nitro. Hydrogen is passed into step S3, and 3',4',5'-trifluorobiphenyl-2-nitro can improve the efficiency of reduction reaction under the action of reduction catalyst, so as to improve the yield of 3',4',5'-trifluorobiphenyl-2-amine.

[0039] In one embodiment of the present application, the above-mentioned step S1 also includes: step S11, subjecting the raw materials including metallic magnesium and 3,4,5-trifluorobromobenzene solution to a Grignard reaction to obtain a first reaction system containing 3,4,5-trifluorophenylmagnesium bromide; step S12, subjecting the raw materials including the first reaction system and trimethyl borate solution to a substitution reaction to obtain a second reaction system; step S13, subjecting the raw materials including the second reaction system and an acidic solution to an acidification reaction to obtain a first product system; step S14, subjecting the first product system to a first concentration treatment, a first recrystallization treatment and a first filtration treatment in sequence to obtain 3,4,5-trifluorophenylborane. Acid; wherein the solvents in the 3,4,5-trifluorobromobenzene solution and the trimethyl borate solution are independently selected from any one or more of tetrahydrofuran, ether and toluene; the feed rate of the 3,4,5-trifluorobromobenzene solution is 100-150 g / min, the metal magnesium is magnesium powder, the feed rate of the metal magnesium is 1-3 g / min, the reaction temperature of the Grignard reaction is 30-65 ° C; the reaction time of the Grignard reaction is 30-90 min; and / or, the feed rate of the first reaction system is 101-153 g / min, the feed rate of the trimethyl borate solution is 50-150 g / min; the reaction temperature of the substitution reaction is - 40~0℃; the reaction time of the substitution reaction is 10~60min; and / or, the feed rate of the second reaction system is 200~350g / min; the feed rate of the acidic solution is 100~250g / min; the acidic solution is selected from any one or more of hydrochloric acid solution, sulfuric acid solution and acetic acid solution; the mass concentration of the acidic solution is 5~20%; the reaction temperature of the acidification reaction is 0~20℃; the reaction time of the acidification reaction is 10~60min; and / or, the feed rate of the first product system is 300~500g / min; the temperature of the first continuous concentration treatment is 40~60℃; the first continuous concentration treatment The pressure of the treatment is -0.06~-0.1MPa; the feed rate of the raw material in the first recrystallization treatment is 40~150g / min; the first recrystallization solvent in the first recrystallization treatment is selected from any one or more of n-heptane, n-hexane and dichloromethane; the mass ratio of the raw material to the first recrystallization solvent in the first recrystallization treatment is 0.42~1.25:1g / min; the temperature of the first recrystallization treatment is 0~40℃; the time of the first recrystallization treatment is 30~60min; and / or, the feed rate of the raw material in the first filtration treatment is 100~2000g / min; the temperature of the first filtration treatment is 0~40℃.

[0040] It is preferred to control the feed rate of 3,4,5-trifluorobromobenzene solution and metal magnesium, the reaction temperature and reaction time of Grignard reaction within the above range, which helps 3,4,5-trifluorobromobenzene solution and metal magnesium to fully carry out Grignard reaction, thereby improving the reaction efficiency of Grignard reaction. It is preferred to control the feed rate of the first reaction system and trimethyl borate solution, the reaction temperature and reaction time of the substitution reaction within the above range, which helps the first reaction system and trimethyl borate solution to fully carry out substitution reaction, thereby improving the reaction efficiency of substitution reaction. It is preferred to control the feed rate of the second reaction system and the acidic solution, the reaction temperature and reaction time of the acidification reaction within the above range, which helps to fully acidify the second reaction system, thereby obtaining the first product system containing 3,4,5-trifluorophenylboric acid. It is preferred to control the feed rate of the first product system, the temperature and pressure of the first continuous concentration treatment within the above range, which helps to fully evaporate the solvent in the first reaction system, thereby helping to increase the mass concentration of 3,4,5-trifluorophenylboric acid. Preferably, the feed rate of the raw material in the first recrystallization treatment, the type of the first recrystallization solvent, the mass ratio of the raw material to the first recrystallization solvent in the first recrystallization treatment, and the temperature and time of the first recrystallization treatment are controlled within the above ranges, which is helpful for separating and purifying the first product system, thereby improving the quality of 3,4,5-trifluorophenylboric acid. Preferably, the feed rate of the raw material in the first filtration treatment and the temperature of the first filtration treatment are controlled within the above ranges, which is helpful for further separating and purifying the first product system, thereby improving the yield and quality of 3,4,5-trifluorophenylboric acid.

[0041] In one embodiment of the present application, the above step S2 also includes: step S21, performing a first batching treatment on a raw material including 3,4,5-trifluorophenylboric acid and solvent A to obtain a first batch; step S22, performing a coupling reaction on a second raw material including the first batch, a metal catalyst, an alkaline additive and an o-nitrobromobenzene solution to obtain a second product system; step S23, sequentially performing a second filtration treatment, a second concentration treatment, a second recrystallization treatment and a third filtration treatment on the second product system to obtain 3',4',5'-trifluorobiphenyl-2-nitro; wherein 3,4,5-trifluorophenylboric acid is a solid, and the feed rate of 3,4,5-trifluorophenylboric acid is 10~25g / min; solvent A is selected from any one or more of 1,4-dioxane, toluene and xylene, and the mass ratio of 3,4,5-trifluorophenylboric acid to solvent A is 0.2~0.33:1; the temperature of the first ingredient treatment is 20~40°C; the time of the first ingredient treatment is 10~30min; and / or, the feed rate of the first ingredient is 50~100g / mL; the feed rate of the o-nitrobromobenzene solution is 40~100g / min; the solvent in the o-nitrobromobenzene solution is selected from one or more of 1,4-dioxane, toluene and xylene; the mass concentration of the o-nitrobromobenzene solution is 16~31%, and the total feed rate of the metal catalyst and the alkaline additive is 10~30 g / min; the metal catalyst is selected from any one or more of Pd(dppf)Cl2, Pd(dba) and Pd(PPh3)4; the alkaline additive is selected from any one or more of potassium phosphate, potassium carbonate and cesium carbonate; the mass ratio of the metal catalyst to the alkaline additive is 1:2~5; the atmosphere of the coupling reaction is nitrogen and / or argon; the reaction temperature of the coupling reaction is 80~120℃; the reaction time of the coupling reaction is 60~180min; and / or, the feed rate of the second product system is 40~140g / min; the temperature of the second filtration treatment is 0~40℃; and / or, the feed rate of the raw material in the second concentration treatment is 130~170g / m in; the temperature of the second concentration treatment is 40~60℃; the pressure of the second concentration treatment is -0.06~0.1MPa; and / or, the feed rate of the raw material in the second recrystallization treatment is 10~30g / min; the second recrystallization solvent in the second recrystallization treatment is selected from any one or more of isopropanol, ethanol and isobutanol; the mass ratio of the raw material to the second recrystallization solvent in the second recrystallization treatment is 0.62~0.8:1; the temperature of the second recrystallization treatment is -10~20℃; the time of the second recrystallization treatment is 30~60min; and / or, the feed rate of the raw material in the third filtration treatment is 10~20g / min; the temperature of the third filtration treatment is 0~20℃.

[0042] It is preferred to control the feed rate of 3,4,5-trifluorophenylboric acid, the type of solvent A, the mass ratio of 3,4,5-trifluorophenylboric acid to solvent A, and the temperature and time of the first ingredient treatment within the above ranges, which helps 3,4,5-trifluorophenylboric acid to be fully dissolved in solvent A, thereby facilitating the subsequent coupling reaction. It is preferred to control the feed rate of the total feed rate of the first ingredient, o-nitrobromobenzene solution, metal catalyst and alkaline additive, the type and mass ratio of the metal catalyst and alkaline additive, and the atmosphere, reaction temperature and reaction time of the coupling reaction within the above ranges, which helps the first ingredient and o-nitrobromobenzene solution to undergo a coupling reaction under the joint action of the metal catalyst and the alkaline additive, thereby improving the reaction efficiency of the coupling reaction. It is preferred to sequentially perform a second filtration treatment, a second recrystallization treatment and a third filtration treatment on the second product system, and it is preferred to control the feed rate of the second product system, the temperature of the second filtration treatment, the feed rate of the raw material in the second concentration treatment, the temperature and pressure of the second concentration treatment, the feed rate of the raw material in the second recrystallization treatment, the type of the second recrystallization solvent, the mass ratio of the raw material to the second recrystallization solvent in the second recrystallization treatment, the temperature and time of the second recrystallization treatment, and the feed rate of the raw material in the third filtration treatment and the temperature of the third filtration treatment within the above ranges, which helps to fully separate and purify the second product system, thereby improving the yield and quality of 3',4',5'-trifluorobiphenyl-2-nitro.

[0043] In one embodiment of the present application, the above-mentioned step S3 also includes: step S31, subjecting the raw material including 3',4',5'-trifluorobiphenyl-2-nitro and solvent B to a second batching process to obtain a second batching; step S32, subjecting the third raw material including the second batching and hydrogen to a reduction reaction with a reduction catalyst to obtain a third product system; step S33, subjecting the third product system to a third concentration process and a drying process in sequence to obtain 3',4',5'-trifluorobiphenyl-2-amine; wherein the feed rate of 3',4',5'-trifluorobiphenyl-2-nitro is 10~15g / min; solvent B is selected from any one or more of methanol, ethanol and ethyl acetate, and the mass ratio of 3',4',5'-trifluorobiphenyl-2-nitro to solvent B is 0.2~0.56:1; the second batching process The temperature is 20~40℃; the time for the second ingredient treatment is 10~30min; and / or the feed rate of the second ingredient is 15~40g / min; the reduction catalyst is selected from any one or more of aluminum-nickel alloy powder, zinc-nickel alloy powder and zinc-aluminum alloy powder; the mass ratio of the two alloy elements in the reduction catalyst is 1:0.95~1.05; the pressure of the reduction reaction is 0.8~1.5MPa; the reaction temperature of the reduction reaction is 60~90℃; the reaction time of the reduction reaction is 60~180min; and / or the feed rate of the third product system is 15~40g / min; the temperature of the third concentration treatment is 40~60℃; the pressure of the third concentration treatment is -0.06~-0.1MPa; and / or the temperature of the drying treatment is 40~60℃, and the time of the drying treatment is 30~90min.

[0044] It is preferred to control the feed rate of 3',4',5'-trifluorobiphenyl-2-nitro, the type of solvent B, the mass ratio of 3',4',5'-trifluorobiphenyl-2-nitro and solvent B, and the temperature and time of the second batching treatment within the above range, which helps 3',4',5'-trifluorobiphenyl-2-nitro to fully dissolve in solvent B, thereby facilitating the subsequent reduction reaction. It is preferred to control the type of reduction catalyst, the mass ratio of the two alloy elements in the reduction catalyst, and the pressure, reaction temperature and reaction time of the reduction reaction within the above range, which helps 3',4',5'-trifluorobiphenyl-2-nitro and hydrogen to fully carry out the reduction reaction under the action of the reduction catalyst, thereby improving the reaction efficiency of the reduction reaction. It is preferred to control the feed rate of the third product system, the temperature and pressure of the third concentration treatment within the above range, which helps the solvent in the third product system to fully evaporate, thereby helping to improve the yield of 3',4',5'-trifluorobiphenyl-2-nitro. The drying process and time are preferably controlled within the above ranges to help remove moisture in the third product system, thereby obtaining 3',4',5'-trifluorobiphenyl-2-nitro in a solid form.

[0045] The beneficial effects of the present application will be further illustrated below in conjunction with embodiments.

[0046] Example 1

[0047] Use Figure 1 The continuous reaction system for continuously producing 3',4',5'-trifluorobiphenyl-2-amine as shown in Figure 2 The shaking stirred reactor shown is used to prepare 3',4',5'-trifluorobiphenyl-2-amine. Specifically:

[0048] In the first continuous module 20, a solid feeder is used to feed 1.2 g / min of magnesium powder through the magnesium feed port into the column reactor 01 of the dynamic tubular reactor oscillating stirring reactor 101 in the first continuous reactor 1, and 128.0 g / min of 3,4,5-trifluorobromobenzene tetrahydrofuran solution is fed into the column reactor 01 through the 3,4,5-trifluorobromobenzene solution feed port, and the two are subjected to a continuous Grignard reaction at 50° C. for 60 min to obtain a first reaction system containing 3,4,5-trifluorophenylmagnesium bromide; wherein the oscillating stirring reactor 101 further includes an oscillation source 02, an agitator 03, an overflow baffle 04 and an overflow pipe 05, the overflow pipe 05 is connected to the oscillating stirring reactor 101 and extends outside the oscillating stirring reactor 101, and the overflow pipe 05 extends outside the oscillating stirring reactor 101 for a length of 5 0mm; the overflow baffle 04 has a certain curvature, and the overflow baffle 04 is covered at a position outside the interface between the overflow pipe 05 and the oscillating stirring reactor 101, wherein the edge of the end of the overflow baffle 04 that is far away from the inlet of the stirring reactor and opposite to the inlet of the stirring reactor is suspended from the inner wall of the oscillating stirring reactor 101, and the remaining edges of the overflow baffle 04 are fixedly arranged on the inner wall of the oscillating stirring reactor 101; the projected area of ​​the overflow baffle 04 on the inner wall of the oscillating stirring reactor 101 where it is located is larger than the cross-sectional area of ​​the pipe mouth of the overflow pipe 05; the maximum radial distance between the overflow baffle 04 and the inner wall where it is located is 20mm; the angle between the extension direction of the end of the overflow baffle 04 that is close to the inlet of the stirring reactor and opposite to the inlet of the stirring reactor and the inner wall of the oscillating stirring reactor 101 where the overflow pipe 05 is located is 45°. A stirring motor is arranged on the top of the agitator 03, and the stirring motor drives the vertically distributed 1 layer of stirring paddles 013 in the columnar reactor 01 to rotate through the stirring shaft. 140.0 g / min of the first reaction system and 99.7 g / min of trimethyl borate solution were introduced into the substitution reaction device 102 for continuous substitution reaction at -20°C for 20 min to obtain a second reaction system containing 3,4,5-trifluorophenyl borate. 239.7 g / min of the second reaction system and 119.3 g / min of 10% hydrochloric acid solution were introduced into the acidification reaction device 103 for continuous acidification reaction at 5°C for 30 min to obtain a first product system. The first product system at 359 g / min is passed into the first continuous concentrating device 4 for a first concentration treatment at 50°C and -0.08 MPa, and after removing tetrahydrofuran from the first product system, it enters the first continuous recrystallization device 5 and is mixed with 45 g / min of the first recrystallization solvent n-heptane for a first recrystallization treatment, and then enters the first continuous filtration device 6 at a feed rate of 404 g / min for a first filtration treatment at 20°C to obtain 3,4,5-trifluorophenylboric acid solid, wherein the first continuous concentrating device 4 is a falling film evaporator, the first continuous recrystallization device 5 is a dynamic reactor, and the first continuous filtration device 6 is a horizontal screw centrifuge.The yield of the two-step Grignard reaction and substitution reaction was 85%.

[0049] In the second continuous module 30, 14.3 g / min of 3,4,5-trifluorophenylboric acid solid and 44.36 g / min of 1,4-dioxane were introduced into the first continuous batching device 7 for first batching treatment at 20°C for 15 min to obtain the first batch. 58.66 g / min of the first batch, 47.64 g / min of o-nitrobromobenzene, 0.938 g / min of Pd(PPh3)4 and 12.94 g / min of potassium phosphate were introduced into the second continuous reactor 2 for coupling reaction at 100°C for 60 min under nitrogen atmosphere to obtain the second product system. The second product system of 120.18 g / min is passed into the second continuous filtration device 8 for the second filtration treatment at 20°C, and then the raw material after the second filtration treatment is passed into the second continuous concentration device 9 at a feeding rate of 136.3 g / min for the second concentration treatment, and then the raw material after the second concentration treatment is passed into the second continuous recrystallization device 10 at a feeding rate of 15 g / min and mixed with 33.72 g / min of the second recrystallization solvent isopropanol for slurrying at 10°C for the second recrystallization treatment for 30 minutes, and the raw material after the second recrystallization treatment is passed into the third continuous filtration device 11 at a feeding rate of 12.4 g / min for the third filtration treatment at 10°C to obtain 3',4',5'-trifluorobiphenyl-2-nitro solid, wherein the second continuous reactor 2 is a dynamic tubular reactor, the first continuous dosing device 7 is a dynamic tubular reactor, the second continuous concentration device 9 is a falling film evaporator, the second continuous recrystallization device 10 is a dynamic reactor, and the second continuous filtration device 8 and the third continuous filtration device 11 are horizontal screw centrifuges. The yield of the continuous coupling reaction was 87%.

[0050] In the third continuous module 40, 17.9 g / min of 3',4',5'-trifluorobiphenyl-2-nitro solid and 42.4 g / min of methanol were introduced into the second continuous batching device 13 and subjected to second batching treatment at 20°C for 15 min to obtain the second batching. 30 g / min of the second batching was introduced into the third continuous reactor 3 and subjected to reduction reaction at 90°C for 120 min using a reduction catalyst aluminum-nickel alloy powder (1:1.05) under a hydrogen atmosphere to obtain a third product system. The third product system of 60.3 g / min was introduced into the third continuous concentrator 14 for the third concentrating treatment at 60°C and -0.08 MPa, and the product after the third concentrating treatment was introduced into the drying device 12 for drying treatment at 50°C for 60 minutes to obtain 3',4',5'-trifluorobiphenyl-2-amine, wherein the third continuous reactor 3 was an axial adiabatic fixed bed reactor, the second continuous dosing device 13 was an autokinetic tubular reactor, and the third continuous concentrator 14 was a falling film evaporator. The yield of 3',4',5'-trifluorobiphenyl-2-amine was 92%.

[0051] Example 2

[0052] Use Figure 1 The continuous reaction system for continuously producing 3',4',5'-trifluorobiphenyl-2-amine as shown in Figure 2 The shaking stirred reactor shown is used to prepare 3',4',5'-trifluorobiphenyl-2-amine. Specifically:

[0053] In the first continuous module 20, a solid feeder is used to feed 1.6 g / min of magnesium powder through the magnesium feed port into the columnar reactor 01 of the dynamic tubular reactor oscillating stirring reactor 101 in the first continuous reactor 1, and 170.24 g / min of 3,4,5-trifluorobromobenzene tetrahydrofuran solution is fed into the columnar reactor 01 through the 3,4,5-trifluorobromobenzene solution feed port. The two are subjected to a continuous Grignard reaction at 60° C. for 45 minutes to obtain a first reaction system containing 3,4,5-trifluorophenylmagnesium bromide; wherein the oscillating stirring reactor 101 further includes an oscillation source 02, an agitator 03, an overflow baffle 04 and an overflow pipe 05, the overflow pipe 05 is connected to the oscillating stirring reactor 101 and extends outside the oscillating stirring reactor 101, and the overflow pipe 05 extends outside the oscillating stirring reactor 101 by a length of 50mm; the overflow baffle 04 has a certain curvature, and the overflow baffle 04 is covered at a position outside the interface between the overflow pipe 05 and the oscillating stirring reactor 101, wherein the edge of the end of the overflow baffle 04 far away from the inlet of the stirring reactor and opposite to the inlet of the stirring reactor is suspended from the inner wall of the oscillating stirring reactor 101, and the remaining edges of the overflow baffle 04 are fixedly arranged on the inner wall of the oscillating stirring reactor 101; the projected area of ​​the overflow baffle 04 on the inner wall of the oscillating stirring reactor 101 where it is located is greater than the cross-sectional area of ​​the pipe mouth of the overflow pipe 05; the maximum radial distance between the overflow baffle 04 and the inner wall where it is located is 30mm; the angle between the extension direction of the end of the overflow baffle 04 close to the inlet of the stirring reactor and opposite to the inlet of the stirring reactor and the inner wall of the oscillating stirring reactor 101 where the overflow pipe 05 is located is 45°. A stirring motor is arranged on the top of the stirrer 03, and the stirring motor drives the three layers of stirring paddles 013 vertically distributed in the columnar reactor 01 to rotate through the stirring shaft. 186.2 g / min of the first reaction system and 132.6 g / min of trimethyl borate solution were introduced into the substitution reaction device 102 for continuous substitution reaction at -20°C for 20 min to obtain a second reaction system containing 3,4,5-trifluorophenylboron. 318.8 g / min of the second reaction system and 158.7 g / min of 10% hydrochloric acid solution were introduced into the acidification reaction device 103 for continuous acidification reaction at 5°C for 30 min to obtain a first product system. The first product system at a rate of 477.5 g / min is passed into the first continuous concentrating device 4 for a first concentration treatment at 50°C and -0.08 MPa, and after removing tetrahydrofuran from the first product system, it enters the first continuous recrystallization device 5 and is mixed with 45 g / min of the first recrystallization solvent n-heptane for a first recrystallization treatment, and then enters the first continuous filtration device 6 at a feed rate of 537.3 g / min for a first filtration treatment at 20°C to obtain 3,4,5-trifluorophenylboric acid solid, wherein the first continuous concentrating device 4 is a falling film evaporator, the first continuous recrystallization device 5 is a dynamic reactor, and the first continuous filtration device 6 is a horizontal screw centrifuge.The yield of the two-step Grignard reaction and substitution reaction was 81%.

[0054] In the second continuous module 30, 18.1 g / min of 3,4,5-trifluorophenylboric acid solid and 55.9 g / min of 1,4-dioxane were introduced into the first continuous batching device 7 for first batching treatment at 20°C for 15 min to obtain the first batch. 73.9 g / min of the first batch, 60.0 g / min of o-nitrobromobenzene, 1.18 g / min of Pd(PPh3)4 and 16.3 g / min of potassium phosphate were introduced into the second continuous reactor 2 for coupling reaction at 100°C for 60 min under nitrogen atmosphere to obtain the second product system. The second product system of 151.4 g / min is passed into the second continuous filtration device 8 for the second filtration treatment at 20°C, and then the raw material after the second filtration treatment is passed into the second continuous concentration device 9 at a feeding rate of 161.3 g / min for the second concentration treatment, and then the raw material after the second concentration treatment is passed into the second continuous recrystallization device 10 at a feeding rate of 20 g / min and mixed with 42.5 g / min of the second recrystallization solvent isopropanol for slurrying at 10°C for the second recrystallization treatment for 30 minutes, and the raw material after the second recrystallization treatment is passed into the third continuous filtration device 11 at a feeding rate of 16.5 g / min for the third filtration treatment at 20°C to obtain 3',4',5'-trifluorobiphenyl-2-nitro solid, wherein the second continuous reactor 2 is a dynamic tubular reactor, the first continuous dosing device 7 is a dynamic tubular reactor, the second continuous concentration device 9 is a falling film evaporator, the second continuous recrystallization device 10 is a dynamic reactor, and the second continuous filtration device 8 and the third continuous filtration device 11 are horizontal screw centrifuges. The yield of the continuous coupling reaction was 87%.

[0055] In the third continuous module 40, 22.6 g / min of 3',4',5'-trifluorobiphenyl-2-nitro solid and 53.4 g / min of methanol were introduced into the second continuous batching device 13 and subjected to second batching treatment at 20°C for 15 min to obtain the second batching. 40 g / min of the second batching was introduced into the third continuous reactor 3 and subjected to reduction reaction at 90°C for 150 min using a reduction catalyst aluminum-nickel alloy powder (1:1) under a hydrogen atmosphere to obtain a third product system. The third product system of 75.9 g / min was introduced into the third continuous concentrator 14 for the third concentrating treatment at 45°C and -0.1 MPa, and the product after the third concentrating treatment was introduced into the drying device 12 for drying treatment at 50°C for 60 minutes to obtain 3',4',5'-trifluorobiphenyl-2-amine, wherein the third continuous reactor 3 was an axial adiabatic fixed bed reactor, the second continuous batching device 13 was an autokinetic tubular reactor, and the third continuous concentrator 14 was a falling film evaporator. The yield of 3',4',5'-trifluorobiphenyl-2-amine was 92%.

[0056] Example 3

[0057] The difference from Example 1 is that the overflow pipe 05 extends out of the oscillating stirring reactor 101 by 30 mm, and no overflow baffle is provided at a position other than the interface between the overflow pipe 05 and the oscillating stirring reactor 101. Finally, 3',4',5'-trifluorobiphenyl-2-amine is obtained, and the yield of the two-step Grignard reaction and the substitution reaction is 79%, the yield of the continuous coupling reaction is 81%, and the yield of 3',4',5'-trifluorobiphenyl-2-amine is 86%.

[0058] Example 4

[0059] The difference from Example 1 is that the reaction temperature in the oscillating stirring reactor 101 is 45° C., and 3',4',5'-trifluorobiphenyl-2-amine is finally obtained. The yield of the Grignard reaction and the substitution reaction is 74%, the yield of the continuous coupling reaction is 75%, and the yield of 3',4',5'-trifluorobiphenyl-2-amine is 74%.

[0060] Example 5

[0061] The difference from Example 1 is that the maximum radial distance between the overflow baffle 04 and the inner wall on which it is located is 50 mm, and 3',4',5'-trifluorobiphenyl-2-amine is finally obtained. The yield of the Grignard reaction and the substitution reaction is 84%, the yield of the continuous coupling reaction is 86%, and the yield of 3',4',5'-trifluorobiphenyl-2-amine is 91%.

[0062] Example 6

[0063] The difference from Example 1 is that the maximum radial distance between the overflow baffle 04 and the inner wall on which it is located is 60 mm, and 3',4',5'-trifluorobiphenyl-2-amine is finally obtained. The yield of the Grignard reaction and the substitution reaction is 79%, the yield of the continuous coupling reaction is 81%, and the yield of 3',4',5'-trifluorobiphenyl-2-amine is 85%.

[0064] Example 7

[0065] The difference from Example 1 is that the angle between the extension direction of the end of the overflow baffle 04 close to the inlet of the stirred reactor and opposite to the inlet of the stirred reactor and the inner wall of the oscillating stirred reactor 101 where the overflow pipe 05 is located is 60°, and 3',4',5'-trifluorobiphenyl-2-amine is finally obtained. The yield of the two-step Grignard reaction and substitution reaction is 84%, the yield of the continuous coupling reaction is 86%, and the yield of 3',4',5'-trifluorobiphenyl-2-amine is 91%.

[0066] Example 8

[0067] The difference from Example 1 is that the angle between the extension direction of the end of the overflow baffle 04 close to the inlet of the stirred reactor and opposite to the inlet of the stirred reactor and the inner wall of the oscillating stirred reactor 101 where the overflow pipe 05 is located is 70°, and 3',4',5'-trifluorobiphenyl-2-amine is finally obtained. The yield of the two-step Grignard reaction and substitution reaction is 81%, the yield of the continuous coupling reaction is 83%, and the yield of 3',4',5'-trifluorobiphenyl-2-amine is 87%.

[0068] Comparative Example 1

[0069] 72g of magnesium powder, 42g of trifluorobromobenzene and 600mL of tetrahydrofuran solution were placed in a reactor, a small amount of iodine particles was added, the temperature was raised to 50°C for initiation, and 1200mL of tetrahydrofuran solution containing 378g of trifluorobromobenzene was continuously introduced after the Grignard reagent was introduced, the temperature in the reactor was 50°C and kept warm for 6h, and after the reaction, no raw materials were left, the system was cooled to 0~-10°C, and 800mL of tetrahydrofuran solution containing 230g of trimethyl borate was slowly added dropwise to the system for 1h, and the temperature was controlled not to exceed -20°C during the addition process. After the addition was completed, the system temperature was controlled not to be higher than -20°C and kept warm for 3h; 1200g of 10% hydrochloric acid was introduced into the reactor for quenching and acidification, and the organic phase was separated and concentrated to obtain 3,4,5-trifluorophenylboric acid solid, and the yield of the Grignard reaction and substitution reaction was 75%.

[0070] 315 g of 3,4,5-trifluorophenylboric acid solid, 980 mL of 1,4-dioxane, 398 g of o-nitrobromobenzene, 41.4 g of tetrakistriphenylphosphine palladium, and 98.7 g of potassium phosphate were placed in a reactor, and the reactor was replaced with nitrogen three times. The temperature in the reactor was 100°C and stirred for 6 hours. After the coupling reaction was completed, the reaction system was filtered and concentrated, and the crude product was recrystallized using isopropanol to obtain 3',4',5'-trifluorobiphenyl-2-nitro solid. The yield of the coupling reaction was 76%.

[0071] 367g of 3',4',5'-trifluorobiphenyl-2-nitro solid, 870g of methanol, and 18.5g of catalyst aluminum-nickel alloy powder were placed in a reactor. The reactor was replaced with nitrogen three times and then with hydrogen three times. The temperature in the reactor was controlled to 90°C and kept warm for 12 hours. After the pressure dropped during the reaction, hydrogen was added to the reactor until the pressure value was 1.5MPa. After the reaction was completed, the system was filtered to recover the catalyst, and the filtrate was concentrated to obtain 285g of 3',4',5'-trifluorobiphenyl-2-amine. The yield of 3',4',5'-trifluorobiphenyl-2-amine was 80%.

[0072] From the comparison between the above embodiments and the comparative examples, it can be seen that the reaction yield of each step of the continuous production of 3',4',5'-trifluorobiphenyl-2-amine in the present application is higher than the reaction yield of each step of the discontinuous production of 3',4',5'-trifluorobiphenyl-2-amine in comparative example 1. In addition, the time taken to produce 3',4',5'-trifluorobiphenyl-2-amine in the present application is shorter, the production efficiency is high, the amount of solvent and catalyst used in the present application is less, and the labor cost input is less, so the preparation cost of the present application is lower, and the corresponding three wastes generated in the present application are less.

[0073] From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects:

[0074] The present invention provides a high-efficiency, low-investment continuous reaction system for the continuous production of 3',4',5'-trifluorobiphenyl-2-amine, wherein the oscillating stirring reactor can provide a favorable reaction environment for liquid-solid or gas-liquid-solid multiphase flow reactions, and can be used not only for homogeneous reactions but also for multiphase reactions, especially for liquid-solid reactions involving solid raw materials with a large specific gravity, which have excellent performance that cannot be replaced by traditional stirring reactors. The oscillating stirring reactor includes a columnar reactor, an oscillation source and an agitator, which can achieve that the solids accumulated at the bottom of the reactor can be reciprocated and contacted with the upper materials again to fully react, so that the axial liquid-solid ratio in the entire reaction chamber is balanced, the reaction efficiency is improved, and at the same time, magnesium can be prevented from being deposited at the bottom of the columnar reactor, resulting in the inability to reciprocate and mix the deposited magnesium by stirring alone during long-term operation, thereby resulting in insufficient raw material reaction and low product yield. In addition, the oscillating stirring reactor of the present invention is a process intensification device with a compact geometric structure, axial periodic oscillation conditions and radial sufficient stirring. When the oscillating stirring reactor is working, the oscillation source is located at the bottom of the reactor, and the generated pulse oscillation is superimposed on the average flow rate to drive the solid materials such as the bottom powder in the reactor to reciprocate up and down, thereby forming an irregular shear rate distribution in the reactor cavity. At the same time, the agitator rotates so that the material in the reactor rotates around the axis with the stirring paddle of the stirring device, so that the central liquid level partially drops, and the free surface forms a parabola to form a vortex, thereby allowing the material to fully react. In summary, the oscillating stirring reactor of the present application can achieve efficient mixing of the raw material 3,4,5-trifluorobromobenzene solution and metallic magnesium, has the advantages of shortening the reaction time, and the first reaction system (Grignard reagent) containing 3,4,5-trifluorophenyl magnesium bromide has a high concentration, and can effectively solve the initiation and heat dissipation problems of the Grignard reaction, and effectively avoid the safety hazards such as the impact of the material caused by the drastic temperature rise of the Grignard reaction. The third continuous reactor can reduce the amount of solvent and reduction catalyst used in the reduction reaction process and post-treatment process, thereby reducing the amount of three wastes generated.

[0075] The above are only embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A continuous reaction system for continuously producing 3',4',5'-trifluorobiphenyl-2-amine, characterized in that: The continuous reaction system comprises: The first continuous module (20) comprises a first continuous reactor (1), wherein the first continuous reactor (1) comprises a first inlet and a first outlet, wherein the first inlet is respectively connected to a first raw material source comprising a magnesium source, a 3,4,5-trifluorobromobenzene solution source, a trimethyl borate solution source and an acidic solution source, and the first continuous reactor (1) is used to sequentially subject the first raw material comprising magnesium, a 3,4,5-trifluorobromobenzene solution, a trimethyl borate solution and an acidic solution to a continuous Grignard reaction, a continuous substitution reaction and a continuous acidification reaction to obtain a first product system containing 3,4,5-trifluorophenylboric acid; The second continuous module (30) comprises a second continuous reactor (2), wherein the second continuous reactor (2) comprises a second inlet and a second outlet, wherein the second inlet is respectively connected to a mixture A source, a solvent A source, an o-nitrochlorobenzene solution source and the first outlet, and the second continuous reactor (2) is used to perform a continuous coupling reaction on raw materials comprising the mixture A, the solvent A, the o-nitrochlorobenzene solution and the first product system to obtain a second product system containing 3',4',5'-trifluorobiphenyl-2-nitro; wherein the mixture A comprises a metal catalyst and an alkaline additive; The third continuous module (40) comprises a third continuous reactor (3), the third continuous reactor (3) comprising a third inlet and a third outlet, the third inlet being connected to a solvent B source, a hydrogen source and the second outlet respectively, the third continuous reactor (3) being used for continuously reducing a raw material comprising solvent B, hydrogen and the second product system to obtain a third product system containing 3',4',5'-trifluorobiphenyl-2-amine; wherein the third continuous reactor (3) is filled with a reduction catalyst; Wherein, the first continuous reactor (1) further comprises: An oscillating stirring reactor (101) comprises a stirring reactor inlet and a stirring reactor outlet, wherein the stirring reactor inlet is connected to the magnesium source and the 3,4,5-trifluorobromobenzene solution source respectively, and the oscillating stirring reactor (101) is used to carry out the Grignard reaction on raw materials including magnesium and the 3,4,5-trifluorobromobenzene solution to obtain a first reaction system containing 3,4,5-trifluorophenylmagnesium bromide; The oscillating stirring reactor (101) comprises: A columnar reactor (01), the columnar reactor (01) comprising a reaction column (011) and a jacket (012) arranged outside the reaction column (011), the jacket (012) being used to pass a temperature control medium to control the temperature of the reaction column (011); a 3,4,5-trifluorobromobenzene solution feed port is arranged at the lower part of the reaction column (011), and a magnesium feed port and a first reaction system outlet are arranged at the upper part of the reaction column (011); the 3,4,5-trifluorobromobenzene solution enters the columnar reactor (01) through the 3,4,5-trifluorobromobenzene solution feed port, and the magnesium enters the columnar reactor (01) through the magnesium feed port; An oscillation source (02), the oscillation source (02) being connected to the bottom end of the reaction column (011); A stirrer (03), one end of the stirrer (03) is fixed to the top of the columnar reactor (01), and the other end of the stirrer (03) extends inside the columnar reactor (01) along the axial direction of the columnar reactor (01), and a stirring motor is arranged on the top of the stirrer (03), and the stirring motor drives M layers of stirring paddles (013) vertically distributed in the columnar reactor (01) to rotate through a stirring shaft, so as to mix the raw materials including the magnesium and the 3,4,5-trifluorobromobenzene solution located in the columnar reactor (01), wherein M≥1.

2. The continuous reaction system according to claim 1, characterized in that: The oscillating stirring reactor (101) further comprises an overflow baffle (04) and an overflow pipe (05); The overflow pipe (05) is connected to the oscillating stirring reactor (101) and extends outside the oscillating stirring reactor (101), and the length of the overflow pipe (05) extending outside the oscillating stirring reactor (101) is 50 to 150 mm; The overflow baffle (04) has a certain curvature, and the overflow baffle (04) is arranged at a position outside the interface between the overflow pipe (05) and the oscillating stirred reactor (101), wherein the edge of one end of the overflow baffle (04) away from the inlet of the stirred reactor and opposite to the inlet of the stirred reactor is suspended from the inner wall of the oscillating stirred reactor (101), and the remaining edge of the overflow baffle (04) is fixedly arranged on the inner wall of the oscillating stirred reactor (101); And / or, the projected area of ​​the overflow baffle (04) on the inner wall of the oscillating stirring reactor (101) where it is located is larger than the cross-sectional area of ​​the pipe opening of the overflow pipe (05); And / or, the maximum radial distance between the overflow baffle (04) and the inner wall on which it is located is 20-50 mm; and / or, the angle between the extending direction of the end of the overflow baffle (04) close to the inlet of the stirred reactor and opposite to the inlet of the stirred reactor and the inner wall of the oscillating stirred reactor (101) where the overflow pipe (05) is located is 30-60°; And / or, the overflow baffle (04) is made of stainless steel and / or polytetrafluoroethylene; the stirring shaft is vertically fixed to the center of the columnar reactor (01) through the support bearing of the columnar reactor (01); and / or, the columnar reactor (01) is made of 316L stainless steel and / or glass; the number of the 3,4,5-trifluorobromobenzene solution feed port and the number of the magnesium feed port are independently 1 to 3; And / or, along the axial direction of the columnar reactor (01), an upper heating jacket and a lower heating jacket are sequentially arranged on the outer wall of the columnar reactor (01), the temperature of the upper heating jacket is lower than the temperature of the lower heating jacket, the upper heating jacket adopts an oil bath temperature control using a high and low temperature integrated machine, and the lower heating jacket adopts circulating hot water temperature control.

3. The continuous reaction system according to claim 2, characterized in that: A first continuous concentration device (4), a first continuous recrystallization device (5) and a first continuous filtration device (6) are sequentially arranged on the connecting pipeline between the first continuous module (20) and the second continuous module (30), and are used to sequentially perform a first concentration treatment, a first recrystallization treatment and a first filtration treatment on the first product system to obtain 3,4,5-trifluorophenylboric acid; and / or, a substitution reaction device (102) and an acidification reaction device (103) are sequentially arranged on the connecting pipeline between the first continuous module (20) and the second continuous module (30); The substitution reaction device (102) is used to continuously perform substitution reaction on the raw materials including the trimethyl borate solution and the first reaction system to obtain a second reaction system containing 3,4,5-trifluorophenylboron; The acidification reaction device (103) is used to carry out the continuous acidification reaction on the raw materials including the acidic solution and the second reaction system to obtain the first product system; And / or, the substitution reaction device (102) and the acidification reaction device (103) are each independently selected from any one or more of a dynamic tubular reactor, a fully mixed flow reactor and a plug flow reactor; And / or, the oscillating stirring reactor (101) is a dynamic tubular reactor and / or a fully mixed flow reactor; and / or, the first continuous concentration device (4) is selected from any one or more of a falling film evaporator, a thin film evaporator and a flash tank; And / or, the first continuous recrystallization device (5) is selected from any one or more of a dynamic reactor, a dynamic tubular reactor, and a plug flow reactor; And / or, the first continuous filtering device (6) is a horizontal screw centrifuge and / or a rotary table filter.

4. The continuous reaction system according to any one of claims 1 to 3, characterized in that: A first continuous batching device (7), a second continuous filtering device (8), a second continuous concentrating device (9), a second continuous recrystallizing device (10) and a third continuous filtering device (11) are sequentially arranged on the connecting pipeline between the second continuous module (30) and the third continuous module (40), and are used to sequentially perform a first batching treatment, a second filtration treatment, a second concentration treatment, a second recrystallization treatment and a third filtration treatment on the second product system to obtain 3',4',5'-trifluorobiphenyl-2-nitro; And / or, the second continuous reactor (2) is a dynamic tubular reactor and / or a fully mixed flow reactor; and / or, the second continuous concentration device (9) is selected from any one or more of a falling film evaporator, a thin film evaporator and a flash tank; And / or, the second continuous recrystallization device (10) is selected from any one or more of a dynamic reactor, a dynamic tubular reactor, and a plug flow reactor; And / or, the second continuous filtering device (8) and the third continuous filtering device (11) are each independently a horizontal screw centrifuge and / or a rotary table filter; And / or, the first continuous batching device (7) is a dynamic tubular reactor and / or a fully mixed flow reactor.

5. The continuous reaction system according to any one of claims 1 to 3, characterized in that: The third continuous module (40) further comprises a material drying device (12); a second continuous batching device (13) and a third continuous concentration device (14) are sequentially arranged on the connecting pipeline between the third continuous module (40) and the material drying device (12); The second continuous batching device (13) is used to perform a second batching process on the raw material including the 3',4',5'-trifluorobiphenyl-2-nitro and the solvent B to obtain a second batch; The third continuous concentration device (14) is used to perform a third concentration treatment on the third product system to obtain a third concentrated product; The drying device (12) is used to dry the product after the third concentration treatment to obtain 3',4',5'-trifluorobiphenyl-2-amine; and / or, the third continuous reactor (3) is selected from any one or more of an axial adiabatic fixed bed reactor, a radial adiabatic fixed bed reactor and a shell-and-tube fixed bed reactor; and / or, the third continuous concentration device (14) is selected from any one or more of a falling film evaporator, a thin film evaporator and a flash tank; And / or, the second continuous batching device (13) is an automatic dynamic tubular reactor and / or a fully mixed flow reactor.

6. The continuous reaction system according to any one of claims 1 to 3, characterized in that: The stirring paddle (013) is made of stainless steel and / or polytetrafluoroethylene, and the shape of the stirring paddle (013) is selected from any one or more of a propulsion type, a turbine type, and a spiral type; the stirring blades of the stirring paddle (013) are detachably or non-detachably mounted on the hub of the stirring shaft arranged in the axial direction or welded to the stirring shaft.

7. A continuous method for preparing 3',4',5'-trifluorobiphenyl-2-amine using the continuous reaction system according to any one of claims 1 to 6, characterized in that: The continuous process comprises: Step S1, subjecting a first raw material including metallic magnesium, 3,4,5-trifluorobromobenzene solution, trimethyl borate solution and acidic solution to Grignard reaction, substitution reaction and acidification reaction in sequence to obtain a first product system containing 3,4,5-trifluorophenylboric acid; Step S2, subjecting the second raw material including the 3,4,5-trifluorophenylboric acid, a metal catalyst, an alkaline additive, a solvent A and an o-nitrochlorobenzene solution to a coupling reaction to obtain a second product system containing 3',4',5'-trifluorobiphenyl-2-nitro; Step S3, subjecting the third raw material including the 3',4',5'-trifluorobiphenyl-2-nitro, hydrogen, solvent B and a reduction catalyst to a reduction reaction to obtain a third product system containing 3',4',5'-trifluorobiphenyl-2-amine.

8. The continuous process according to claim 7, characterized in that: The step S1 further comprises: Step S11, subjecting the raw materials including the metal magnesium and the 3,4,5-trifluorobromobenzene solution to the Grignard reaction to obtain a first reaction system containing 3,4,5-trifluorophenylmagnesium bromide; Step S12, subjecting the raw materials including the first reaction system and the trimethyl borate solution to the substitution reaction to obtain a second reaction system; Step S13, subjecting the raw materials including the second reaction system and the acidic solution to the acidification reaction to obtain the first product system; Step S14, sequentially performing a first concentration treatment, a first recrystallization treatment and a first filtration treatment on the first product system to obtain 3,4,5-trifluorophenylboric acid; The solvents in the 3,4,5-trifluorobromobenzene solution and the trimethyl borate solution are independently selected from any one or more of tetrahydrofuran, ether and toluene; the feed rate of the 3,4,5-trifluorobromobenzene solution is 100-150 g / min, the metal magnesium is magnesium powder, the feed rate of the metal magnesium is 1-3 g / min, the reaction temperature of the Grignard reaction is 30-65° C.; the reaction time of the Grignard reaction is 30-90 min; And / or, the feed rate of the first reaction system is 101-153 g / min, the feed rate of the trimethyl borate solution is 50-150 g / min; the reaction temperature of the substitution reaction is -40-0°C; the reaction time of the substitution reaction is 10-60 min; And / or, the feed rate of the second reaction system is 200-350 g / min; the feed rate of the acidic solution is 100-250 g / min; the acidic solution is selected from any one or more of hydrochloric acid solution, sulfuric acid solution and acetic acid solution; the mass concentration of the acidic solution is 5-20%; the reaction temperature of the acidification reaction is 0-20° C.; the reaction time of the acidification reaction is 10-60 min; and / or, the feed rate of the first product system is 300-500 g / min; the temperature of the first continuous concentration treatment is 40-60° C.; the pressure of the first continuous concentration treatment is -0.06--0.1 MPa; the feed rate of the raw material in the first recrystallization treatment is 40-150 g / min; the first recrystallization solvent in the first recrystallization treatment is selected from any one or more of n-heptane, n-hexane and dichloromethane; the mass ratio of the raw material to the first recrystallization solvent in the first recrystallization treatment is 0.42-1.25:1 g / min; the temperature of the first recrystallization treatment is 0-40° C.; the time of the first recrystallization treatment is 30-60 min; And / or, the feed rate of the raw material in the first filtering treatment is 100-2000 g / min; the temperature of the first filtering treatment is 0-40°C.

9. The continuous process according to claim 8, characterized in that: The step S2 further comprises: Step S21, performing a first batching process on the raw materials including the 3,4,5-trifluorophenylboric acid and the solvent A to obtain a first batch; Step S22, performing the coupling reaction on the second raw material including the first ingredient, the metal catalyst, the alkaline additive and the o-nitrobromobenzene solution to obtain the second product system; Step S23, sequentially performing a second filtration treatment, a second concentration treatment, a second recrystallization treatment and a third filtration treatment on the second product system to obtain 3',4',5'-trifluorobiphenyl-2-nitro; Wherein, the 3,4,5-trifluorophenylboric acid is solid, and the feeding rate of the 3,4,5-trifluorophenylboric acid is 10-25 g / min; the solvent A is selected from any one or more of 1,4-dioxane, toluene and xylene, and the mass ratio of the 3,4,5-trifluorophenylboric acid to the solvent A is 0.2-0.33:1; the temperature of the first batch treatment is 20-40° C.; the time of the first batch treatment is 10-30 min; And / or, the feed rate of the first ingredient is 50~100g / mL; the feed rate of the o-nitrobromobenzene solution is 40~100g / min; the solvent in the o-nitrobromobenzene solution is selected from any one or more of 1,4-dioxane, toluene and xylene; the mass concentration of the o-nitrobromobenzene solution is 16~31%, and the total feed rate of the metal catalyst and the alkaline additive is 10~30g / min; the metal catalyst is selected from any one or more of Pd(dppf)Cl2, Pd(dba) and Pd(PPh3)4; the alkaline additive is selected from any one or more of potassium phosphate, potassium carbonate and cesium carbonate; the mass ratio of the metal catalyst to the alkaline additive is 1:2~5; the atmosphere of the coupling reaction is nitrogen and / or argon; the reaction temperature of the coupling reaction is 80~120℃; the reaction time of the coupling reaction is 60~180min; and / or, the feed rate of the second product system is 40-140 g / min; the temperature of the second filtration treatment is 0-40° C.; and / or, the feed rate of the raw material in the second concentration treatment is 130-170 g / min; the temperature of the second concentration treatment is 40-60° C.; the pressure of the second concentration treatment is -0.06-0.1 MPa; And / or, the feed rate of the raw material in the second recrystallization treatment is 10-30 g / min; the second recrystallization solvent in the second recrystallization treatment is selected from any one or more of isopropanol, ethanol and isobutanol; the mass ratio of the raw material to the second recrystallization solvent in the second recrystallization treatment is 0.62-0.8:1; the temperature of the second recrystallization treatment is -10-20° C.; the time of the second recrystallization treatment is 30-60 min; And / or, the feed rate of the raw material in the third filtration treatment is 10-20 g / min; the temperature of the third filtration treatment is 0-20°C.

10. The continuous process according to any one of claims 7 to 9, characterized in that The step S3 further comprises: Step S31, subjecting the raw material including the 3',4',5'-trifluorobiphenyl-2-nitro and the solvent B to a second batching process to obtain a second batch; Step S32, performing the reduction reaction on the third raw material including the second ingredient and the hydrogen and the reduction catalyst to obtain the third product system; Step S33, sequentially performing a third concentration treatment and a drying treatment on the third product system to obtain 3',4',5'-trifluorobiphenyl-2-amine; The feed rate of the 3',4',5'-trifluorobiphenyl-2-nitro is 10-15 g / min; the solvent B is selected from any one or more of methanol, ethanol and ethyl acetate, and the mass ratio of the 3',4',5'-trifluorobiphenyl-2-nitro to the solvent B is 0.2-0.56:1; the temperature of the second batch treatment is 20-40°C; the time of the second batch treatment is 10-30 min; And / or, the feed rate of the second ingredient is 15-40 g / min; the reduction catalyst is selected from any one or more of aluminum-nickel alloy powder, zinc-nickel alloy powder and zinc-aluminum alloy powder; the mass ratio of the two alloy elements in the reduction catalyst is 1:0.95-1.05; the pressure of the reduction reaction is 0.8-1.5 MPa; the reaction temperature of the reduction reaction is 60-90° C.; the reaction time of the reduction reaction is 60-180 min; and / or, the feed rate of the third product system is 15-40 g / min; the temperature of the third concentration treatment is 40-60° C.; the pressure of the third concentration treatment is -0.06--0.1 MPa; And / or, the temperature of the drying treatment is 40-60° C., and the time of the drying treatment is 30-90 min.

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