A continuous synthesis system and method for halogenated benzoic acid compounds

Abstract

The present invention relates to a continuous synthesis system and method of halogenated benzoic acid compounds, and belongs to the technical field of organic synthesis. The continuous synthesis system is a microreactor synthesis system, which mainly includes a metering pump, a T-type micromixer, a magnetically driven active micromixer, a temperature control device, a magnetically driven oscillating microreactor, a nitrogen back pressure tank and a pipeline; it can not only significantly reduce the process safety risk, greatly improve the reaction process efficiency, but also has simple process operation, stable and reliable, and is easy to realize the industrial production of halogenated benzoic acid compounds. The method is based on continuous flow technology, uses performic acid as an oxidizing agent, and directly oxidizes and prepares benzoic acid compounds in a microreactor synthesis system, which can achieve efficient and safe production.

Description

Technical Field

[0001] The present invention relates to a continuous synthesis system and method of halogenated benzoic acid compounds, and more specifically, to a method for preparing halogenated benzoic acid compounds by continuous oxidation based on a microreactor synthesis system and taking halogenated benzaldehyde compounds as raw materials; the method belongs to the technical field of organic synthesis. Background Art

[0002] Benzoic acid compounds are a very important class of compounds in fine chemical raw materials, and are widely used in the preparation of high value-added products such as pharmaceutical intermediates, pesticide intermediates, flavors and fragrances, and specialty chemicals. There are many synthetic routes for benzoic acid compounds. Taking the synthesis of benzoic acid as an example, according to the different raw materials selected, it can be divided into toluene liquid phase oxidation method, benzonitrile hydrolysis method, phthalic anhydride hydrolysis method, and benzyl alcohol oxidation method. The Chinese patent with publication number CN 108467342B provides a method for synthesizing benzoic acid compounds by ultrasonic-assisted oxidation of benzyl alcohol compounds. Benzyl alcohol compounds are used as raw materials, a reaction accelerator is added under ultrasonic-assisted conditions, and benzoic acid compounds are obtained by oxidation in an oxygen-containing atmosphere at a reaction temperature of not less than 60°C. The reaction efficiency is high and environmentally friendly. The Chinese patent with publication number CN 114057569B provides a method for synthesizing benzoic acid and methyl benzoate compounds using TBADT as a catalyst. Toluene compounds are reacted in a mixture of acetonitrile and an aqueous solution of an acidic compound under an oxygen atmosphere and visible light irradiation for 12 h to 48 h to obtain benzoic acid compounds. The reaction conditions are mild and the yield is high. However, the above-mentioned various synthesis methods have problems such as the use of heavy metal catalysts, low reaction efficiency, high temperature and high pressure operating conditions, and / or easy deactivation of the catalyst. Therefore, researchers need to further study and develop more efficient and green synthesis methods.

[0003] Selective oxidation of benzaldehyde compounds is also an important way to prepare benzoic acid compounds. Potassium permanganate, sodium chlorite and molecular oxygen are all commonly used oxidizing agents in this way, but such oxidation processes often require the addition of transition metal catalysts to effectively promote the oxidation process. In addition, there are also methods for preparing benzoic acid compounds using performic acid as an oxidizing agent, which has significant advantages in production cost and environmental friendliness; however, due to the poor stability of performic acid and its easy decomposition and explosion when heated rapidly, it faces significant safety risks when used directly and requires strict supervision.

[0004] Continuous flow technology has shown good application prospects in applying high-risk synthetic chemical pathways to improve traditional synthetic processes due to its superior heat and mass transfer performance, easy parallel scale-up and intrinsic safety. Microreactors are micro-channel reactors based on continuous flow technology, which are used to replace traditional reactors such as glass flasks, funnels and traditional batch reactors commonly used in industrial organic synthesis. There are a large number of micro-reaction channels made with precision machining technology in microreactors, which can provide a large specific surface area and extremely high mass and heat transfer efficiency. In addition, microreactors use continuous flow instead of intermittent operation, making it possible to accurately control the residence time of reactants. These characteristics enable organic synthesis reactions to be precisely controlled at the microscopic scale, providing the possibility of improving reaction selectivity and operational safety.

[0005] At present, there is no microreactor synthesis system and method suitable for preparing halogenated benzoic acid compounds by continuous oxidation using halogenated benzaldehyde compounds as raw materials. Summary of the invention

[0006] In order to overcome the defects of the prior art, one of the objects of the present invention is to provide a continuous synthesis system for halogenated benzoic acid compounds; the continuous synthesis system is a microreactor synthesis system, which can not only significantly reduce the process safety risk and greatly improve the reaction process efficiency, but also has simple process operation, stable and reliable, and is easy to realize the industrial production of halogenated benzoic acid compounds.

[0007] The second object of the present invention is to provide a continuous synthesis method of halogenated benzoic acid compounds, which is based on continuous flow technology, uses performic acid as an oxidizing agent, and directly oxidizes and prepares benzoic acid compounds in a microreactor synthesis system, thereby achieving efficient and safe production.

[0008] To achieve the purpose of the present invention, the following technical solutions are provided.

[0009] A continuous synthesis system for halogenated benzoic acid compounds, the continuous synthesis system is a microreactor synthesis system, the main components of which include: a metering pump, a T-type micromixer, a magnetically driven active micromixer, a temperature control device, a magnetically driven oscillating microreactor, a nitrogen back pressure tank and a pipeline;

[0010] There are four metering pumps, which are used for metering and pumping different materials, specifically a first metering pump, a second metering pump, a third metering pump and a fourth metering pump;

[0011] There are two T-type micro mixers, which are used to mix materials at different reaction stages, specifically a first T-type micro mixer and a second T-type micro mixer;

[0012] The magnetically driven active micro mixer is provided with a device for fully mixing the materials;

[0013] The temperature control device is used to control the oxidation reaction temperature;

[0014] The magnetically driven oscillating microreactor is provided with a device for oscillating to carry out oxidation reaction;

[0015] A nitrogen back pressure tank is provided to provide nitrogen back pressure to achieve the collection of products while maintaining the pressure stability of the reaction system in the continuous synthesis system;

[0016] A plurality of pipelines are provided for connecting the components in the continuous synthesis system and transmitting various reaction materials.

[0017] In the continuous synthesis system, the connection relationship of each main component is as follows:

[0018] One end of the first metering pump is connected to formic acid through a pipeline, and the other end is connected to an inlet of the first T-type micro mixer through a pipeline; one end of the second metering pump is connected to hydrogen peroxide through a pipeline, and the other end is connected to the other inlet of the first T-type micro mixer through a pipeline; the outlet of the first T-type micro mixer is connected to the inlet of the magnetically driven active micro mixer through a pipeline; one end of the third metering pump is connected to a halogenated benzaldehyde solution prepared with ethyl acetate as a solvent through a pipeline, and the other end is connected to the inlet of the magnetically driven active micro mixer through a pipeline;

[0019] The outlet of the magnetically driven active micro-mixer is connected to the inlet of the magnetically driven oscillating micro-reactor through a pipeline, and the outlet of the magnetically driven oscillating micro-reactor is connected to an inlet at one end of the second T-shaped micro-mixer through a pipeline. A temperature control device is arranged around the magnetically driven oscillating micro-reactor to control the temperature of the oxidation reaction;

[0020] One end of the fourth metering pump is connected to ethyl acetate through a pipeline, and the other end is connected to the other end inlet of the second T-type micro mixer through a pipeline, and the outlet of the second T-type micro mixer is connected to the nitrogen back pressure tank through a pipeline; the nitrogen back pressure tank is connected to the nitrogen through a pipeline, and the nitrogen back pressure tank is provided with a pipeline extending from the tank to the outside of the tank and connected to the outside air, and a back pressure regulating valve is provided on the pipeline, and a pipeline for collecting products is provided on the side of the nitrogen back pressure tank, and two stop valves are sequentially arranged on the pipeline, and the two stop valves are switched in turn to achieve the collection of products while maintaining the stability of the pressure of the reaction system.

[0021] Preferably, the halogenated group in the halogenated benzoic acid compound is at least one of fluorine, chlorine and bromine;

[0022] Formic acid, hydrogen peroxide, halogenated benzaldehyde solution and ethyl acetate can all be placed in corresponding storage tanks and stored under nitrogen protection;

[0023] The nitrogen is 99.999% pure and can be placed in a nitrogen cylinder and transported to a nitrogen back pressure tank through a pipeline. A nitrogen pressure reducing valve is installed on the pipeline.

[0024] A continuous synthesis method of a halogenated benzoic acid compound, the method is carried out using a continuous synthesis system of a halogenated benzoic acid compound according to the present invention, and the steps are as follows:

[0025] (1) Formic acid and hydrogen peroxide are respectively delivered to a first T-type micro-mixer by a first metering pump and a second metering pump for thorough mixing. The mixed materials are then delivered to a magnetically driven active micro-mixer together with a halogenated benzaldehyde solution delivered by a third metering pump for mixing to obtain a thoroughly mixed reaction solution.

[0026] Preferably, the molar concentration of the halogenated benzaldehyde solution is 0.75 mol / L to 1.0 mol / L;

[0027] Preferably, the molar ratio of halogenated benzaldehyde to hydrogen peroxide is 1.0: 1.0 to 1.3;

[0028] Preferably, the molar ratio of halogenated benzaldehyde to formic acid is 1.0:8.0-12.0;

[0029] Preferably, the rotation speed of the magnetic rotor in the magnetically driven active micromixer is 300 r / min to 700 r / min;

[0030] (2) The fully mixed reaction liquid enters a magnetically driven oscillating microreactor for oxidation reaction. The magnetic rotor in the magnetically driven oscillating microreactor is driven to oscillate repeatedly in the microreaction channel by regulating an external magnetic field, thereby enhancing the transfer characteristics of the reaction system and avoiding the deposition of solid impurities generated during the reaction. The temperature of the oxidation reaction is controlled by a temperature control device to obtain a reaction liquid after the oxidation reaction.

[0031] Preferably, the oscillation frequency of the magnetic rotor in the magnetically driven oscillating microreactor is 10 Hz to 25 Hz;

[0032] Preferably, the reaction temperature of the oxidation reaction is 80°C to 120°C, and the reaction time is 15 min to 30 min;

[0033] (3) The reaction liquid after the oxidation reaction flows out of the magnetically driven oscillating microreactor, is fully mixed with the ethyl acetate delivered by the fourth metering pump in the second T-type micromixer, and then enters the nitrogen back pressure tank. The pipeline on the side of the nitrogen back pressure tank is switched alternately by two stop valves to achieve the collection of products while maintaining the stability of the system pressure. Nitrogen is delivered to the nitrogen back pressure tank, and the pressure of the reaction system is controlled to 150 psi in combination with the back pressure regulating valve to prevent the solvent in the reaction system from vaporizing;

[0034] (4) The collected product is a solution containing halogenated benzoic acid, which is purified to prepare halogenated benzoic acid.

[0035] Beneficial Effects

[0036] (1) The present invention provides a continuous synthesis system for halogenated benzoic acid compounds. The continuous synthesis system is a microreactor synthesis system, which can not only significantly reduce process safety risks and greatly improve the efficiency of the reaction process, but also has simple process operation, is stable and reliable, and is easy to realize the industrial production of halogenated benzoic acid compounds;

[0037] (2) The present invention provides a continuous synthesis system for halogenated benzoic acid compounds. In the continuous synthesis system, an external magnetic field is introduced to drive a magnetic rotor to rotate in a magnetically driven active micromixer and to oscillate in a magnetically driven oscillating microreactor, so as to strengthen the mixing and transfer process and further improve the heat and mass transfer efficiency of the microreactor. Since an oxidation reaction with a peroxy acid occurs at a high temperature, insoluble solid byproducts are easily generated. The magnetic rotor oscillation introduced in the reaction system by an external magnetic field can avoid the solid deposition generated during the reaction process.

[0038] (3) The present invention provides a continuous synthesis system for halogenated benzoic acid compounds, in which a nitrogen back pressure tank is introduced at the tail end, and the nitrogen back pressure is used to achieve long-term stable operation of a reaction system involving solids under a continuous flow system;

[0039] (4) The present invention provides a continuous synthesis method of halogenated benzoic acid compounds. The method is based on continuous flow technology. In a microreactor synthesis system, performic acid is used as an oxidizing agent, formic acid and hydrogen peroxide are reacted to generate performic acid in situ, and then oxidized with a halogenated benzaldehyde solution at high temperature to directly prepare halogenated benzoic acid compounds. The reaction process is highly economical and environmentally friendly, and can achieve efficient and safe production.

[0040] (5) The present invention provides a continuous synthesis method for halogenated benzoic acid compounds, wherein the reaction temperature of the oxidation reaction is 80°C to 120°C, and the reaction time is 15 min to 30 min. By increasing the reaction temperature in a continuous flow system, the reaction can be effectively accelerated, the process efficiency can be improved, the liquid holding volume in the continuous flow reactor is greatly reduced, and the intrinsic safety characteristics of the process are effectively enhanced. The continuous operation is simple and the process is controllable, and the process is more green and efficient. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 This is a schematic diagram of a continuous synthesis system of a halogenated benzoic acid compound in Example 1.

[0042] Among them, 1 is a formic acid storage tank, 2 is a hydrogen peroxide storage tank, 3 is a halogenated benzaldehyde solution storage tank, 4 is a first metering pump, 5 is a second metering pump, 6 is a third metering pump, 7 is a first T-type micro mixer, 8 is a magnetically driven active micro mixer, 9 is an ethyl acetate storage tank, 10 is a temperature control device, 11 is a magnetically driven oscillating microreactor, 12 is a fourth metering pump, 13 is a second T-type micro mixer, 14 is a first stop valve, 15 is a second stop valve, 16 is a product collection tank, 17 is a nitrogen back pressure tank, 18 is a back pressure regulating valve, 19 is a nitrogen pressure reducing valve, and 20 is a nitrogen cylinder. DETAILED DESCRIPTION

[0043] Example 1

[0044] like Figure 1 As shown, a continuous synthesis system of halogenated benzoic acid compounds is a microreactor synthesis system, and its main components include: a metering pump, a T-type micromixer, a magnetically driven active micromixer 8, a temperature control device 10, a magnetically driven oscillating microreactor 11, a nitrogen back pressure tank 17 and pipelines;

[0045] There are four metering pumps, which are used for metering and pumping different materials, specifically a first metering pump 4, a second metering pump 5, a third metering pump 6 and a fourth metering pump 12;

[0046] There are two T-shaped micro mixers, which are used to mix materials at different reaction stages, specifically a first T-shaped micro mixer 7 and a second T-shaped micro mixer 13;

[0047] A magnetically driven active micro mixer 8 is provided for fully mixing the materials;

[0048] The temperature control device 10 is a constant temperature circulating bath, which is used to control the oxidation reaction temperature;

[0049] The magnetically driven oscillating microreactor 11 is provided with a device for oscillating to carry out oxidation reaction;

[0050] A nitrogen back pressure tank 17 is provided to provide nitrogen back pressure to achieve the collection of products while maintaining the pressure stability of the reaction system in the continuous synthesis system;

[0051] A plurality of pipelines are provided for connecting the components in the continuous synthesis system and transmitting various reaction materials;

[0052] In the continuous synthesis system, the connection relationship of each component is as follows:

[0053] One end of the first metering pump 4 is connected to formic acid through a pipeline, and the other end is connected to an inlet of a first T-type micro mixer 7 through a pipeline. One end of the second metering pump 5 is connected to hydrogen peroxide through a pipeline, and the other end is connected to the other inlet of the first T-type micro mixer 7 through a pipeline. The outlet of the first T-type micro mixer 7 is connected to the inlet of the magnetically driven active micro mixer 8 through a pipeline. One end of the third metering pump 6 is connected to a halogenated benzaldehyde solution prepared with ethyl acetate as a solvent through a pipeline, and the other end is connected to the inlet of the magnetically driven active micro mixer 8 through a pipeline.

[0054] The outlet of the magnetically driven active micro-mixer 8 is connected to the inlet of the magnetically driven oscillating micro-reactor 11 through a pipeline, and the outlet of the magnetically driven oscillating micro-reactor 11 is connected to an inlet of one end of the second T-shaped micro-mixer 13 through a pipeline. A temperature control device 10 is provided around the magnetically driven oscillating micro-reactor 11 to control the temperature of the oxidation reaction;

[0055] One end of the fourth metering pump 12 is connected to ethyl acetate through a pipeline, and the other end is connected to the other end inlet of the second T-type micro mixer 13 through a pipeline; the outlet of the second T-type micro mixer 13 is connected to the nitrogen back pressure tank 17 through a pipeline; the nitrogen back pressure tank 17 is connected to nitrogen through a pipeline, and a pipeline extending from the tank to the outside of the tank and communicating with the outside air is provided on the top of the nitrogen back pressure tank 17, and a back pressure regulating valve 18 is provided on the pipeline, and a pipeline connected to the product collection tank 16 is provided on the side of the nitrogen back pressure tank 17 near the bottom, which is used to collect the prepared product, and two stop valves are successively provided on the pipeline, namely the first stop valve 14 and the second stop valve 15, and the two stop valves are switched in turn to achieve the collection of products while maintaining the stability of the pressure of the reaction system;

[0056] Formic acid is placed in a formic acid storage tank 1, hydrogen peroxide is placed in a hydrogen peroxide storage tank 2, a halogenated benzaldehyde solution is placed in a halogenated benzaldehyde solution storage tank 3, and ethyl acetate is placed in an ethyl acetate storage tank 9, all of which are stored under nitrogen protection;

[0057] The nitrogen gas has a purity of 99.999%, is placed in a nitrogen cylinder 20, and is transported to a nitrogen back pressure tank 17 through a pipeline, and a nitrogen pressure reducing valve 19 is provided on the pipeline.

[0058] Example 2

[0059] A continuous synthesis method of a halogenated benzoic acid compound, the method is carried out using a continuous synthesis system of a halogenated benzoic acid compound described in Example 1, and the steps are as follows:

[0060] (1) Formic acid and hydrogen peroxide are respectively transported to the first T-type micro mixer 7 by the first metering pump 4 and the second metering pump 5 for thorough mixing. The mixed materials are then transported together with the halogenated benzaldehyde solution transported by the third metering pump 6 into the magnetically driven active micro mixer 8 for mixing to obtain a thoroughly mixed reaction solution.

[0061] The halogenated benzaldehyde solution is a 0.95 mol / L fluorobenzaldehyde solution prepared with ethyl acetate as solvent;

[0062] The rotation speed of the magnetic rotor in the magnetically driven active micromixer 8 is 500 r / min;

[0063] By controlling the flow ratio among the first metering pump 4, the second metering pump 5 and the third metering pump 6, the molar ratio of fluorobenzaldehyde, hydrogen peroxide and formic acid is controlled to be 1.0: 1.1: 8.0;

[0064] (2) The fully mixed reaction liquid enters the magnetically driven oscillating microreactor 11 for oxidation reaction. By adjusting the external magnetic field, the magnetic rotor in the magnetically driven oscillating microreactor 11 is driven to oscillate repeatedly in the microreaction channel, thereby enhancing the transfer characteristics of the reaction system and avoiding the deposition of solid impurities generated during the reaction process. The temperature of the oxidation reaction is controlled by the temperature control device 10 to obtain the reaction liquid after the oxidation reaction.

[0065] The oscillation frequency of the magnetic rotor in the magnetically driven oscillating microreactor 11 is 24 Hz;

[0066] The reaction temperature of the oxidation reaction is 105°C, and the reaction time is controlled to be 22 min by adjusting the flow rates of the first metering pump 4, the second metering pump 5 and the third metering pump 6;

[0067] (3) The reaction liquid after the oxidation reaction flows out from the magnetically driven oscillating microreactor 11, is fully mixed with the ethyl acetate delivered by the fourth metering pump 12 in the second T-type micromixer 13, and then enters the nitrogen back pressure tank 17. The pipeline on the side of the nitrogen back pressure tank 17 is switched alternately by the first stop valve 14 and the second stop valve 15 to achieve product collection while maintaining the stability of the reaction system pressure. The product is collected in the product collection tank 16, and the nitrogen is delivered to the nitrogen back pressure tank 17. The pressure of the reaction system is controlled to 150 psi in combination with the back pressure regulating valve 18 to prevent the solvent in the reaction system from vaporizing;

[0068] (4) The product collected in the product collection tank 16 is a solution containing fluorobenzoic acid. Quantitative analysis using high performance liquid chromatography shows that the yield of fluorobenzoic acid is 93.1%. The solution containing fluorobenzoic acid is subjected to rotary evaporation and purified by a chromatographic column to obtain the final product, fluorobenzoic acid.

[0069] Example 3

[0070] A continuous synthesis method of a halogenated benzoic acid compound, the method is carried out using a continuous synthesis system of a halogenated benzoic acid compound described in Example 1, and the steps are as follows:

[0071] (1) Formic acid and hydrogen peroxide are respectively transported to the first T-type micro mixer 7 by the first metering pump 4 and the second metering pump 5 for thorough mixing. The mixed materials are then transported together with the halogenated benzaldehyde solution transported by the third metering pump 6 into the magnetically driven active micro mixer 8 for mixing to obtain a thoroughly mixed reaction solution.

[0072] The halogenated benzaldehyde solution is a 0.9 mol / L fluorobenzaldehyde solution prepared with ethyl acetate as solvent;

[0073] The speed of the magnetic rotor in the magnetically driven active micromixer 8 is 700 r / min;

[0074] By controlling the flow ratio among the first metering pump 4, the second metering pump 5 and the third metering pump 6, the molar ratio of fluorobenzaldehyde, hydrogen peroxide and formic acid is controlled to be 1.0: 1.3: 10.0;

[0075] (2) The fully mixed reaction liquid enters the magnetically driven oscillating microreactor 11 for oxidation reaction. By adjusting the external magnetic field, the magnetic rotor in the magnetically driven oscillating microreactor 11 is driven to oscillate repeatedly in the microreaction channel, thereby enhancing the transfer characteristics of the reaction system and avoiding the deposition of solid impurities generated during the reaction process. The temperature of the oxidation reaction is controlled by the temperature control device 10 to obtain the reaction liquid after the oxidation reaction.

[0076] The oscillation frequency of the magnetic rotor in the magnetically driven oscillating microreactor 11 is 24 Hz;

[0077] The reaction temperature of the oxidation reaction is 95°C, and the reaction time is controlled to be 28 min by adjusting the flow rates of the first metering pump 4, the second metering pump 5 and the third metering pump 6;

[0078] (3) The reaction liquid after the oxidation reaction flows out from the magnetically driven oscillating microreactor 11, is fully mixed with the ethyl acetate delivered by the fourth metering pump 12 in the second T-type micromixer 13, and then enters the nitrogen back pressure tank 17. The pipeline on the side of the nitrogen back pressure tank 17 is switched alternately by the first stop valve 14 and the second stop valve 15 to achieve product collection while maintaining the stability of the reaction system pressure. The product is collected in the product collection tank 16, and the nitrogen is delivered to the nitrogen back pressure tank 17. The pressure of the reaction system is controlled to 150 psi in combination with the back pressure regulating valve 18 to prevent the solvent in the reaction system from vaporizing;

[0079] (4) The product collected in the product collection tank 16 is a solution containing fluorobenzoic acid. Quantitative analysis using high performance liquid chromatography shows that the yield of fluorobenzoic acid is 90.1%. The solution containing fluorobenzoic acid is subjected to rotary evaporation and purified by a chromatographic column to obtain the final product, fluorobenzoic acid.

[0080] Example 4

[0081] A continuous synthesis method of a halogenated benzoic acid compound, the method is carried out using a continuous synthesis system of a halogenated benzoic acid compound described in Example 1, and the steps are as follows:

[0082] (1) Formic acid and hydrogen peroxide are respectively transported to the first T-type micro mixer 7 by the first metering pump 4 and the second metering pump 5 for thorough mixing. The mixed materials are then transported together with the halogenated benzaldehyde solution transported by the third metering pump 6 into the magnetically driven active micro mixer 8 for mixing to obtain a thoroughly mixed reaction solution.

[0083] The halogenated benzaldehyde solution is a 0.95 mol / L fluorobenzaldehyde solution prepared with ethyl acetate as solvent;

[0084] The rotation speed of the magnetic rotor in the magnetically driven active micromixer 8 is 500 r / min;

[0085] By controlling the flow ratio among the first metering pump 4, the second metering pump 5 and the third metering pump 6, the molar ratio of fluorobenzaldehyde, hydrogen peroxide and formic acid is controlled to be 1.0: 1.2: 8.0;

[0086] (2) The fully mixed reaction liquid enters the magnetically driven oscillating microreactor 11 for oxidation reaction. By adjusting the external magnetic field, the magnetic rotor in the magnetically driven oscillating microreactor 11 is driven to oscillate repeatedly in the microreaction channel, thereby enhancing the transfer characteristics of the reaction system and avoiding the deposition of solid impurities generated during the reaction process. The temperature of the oxidation reaction is controlled by the temperature control device 10 to obtain the reaction liquid after the oxidation reaction.

[0087] The oscillation frequency of the magnetic rotor in the magnetically driven oscillating microreactor 11 is 18 Hz;

[0088] The reaction temperature of the oxidation reaction is 115°C, and the reaction time is controlled to be 19 min by adjusting the flow rates of the first metering pump 4, the second metering pump 5 and the third metering pump 6;

[0089] (3) The reaction liquid after the oxidation reaction flows out from the magnetically driven oscillating microreactor 11, is fully mixed with the ethyl acetate delivered by the fourth metering pump 12 in the second T-type micromixer 13, and then enters the nitrogen back pressure tank 17. The pipeline on the side of the nitrogen back pressure tank 17 is switched alternately by the first stop valve 14 and the second stop valve 15 to achieve product collection while maintaining the stability of the reaction system pressure. The product is collected in the product collection tank 16, and the nitrogen is delivered to the nitrogen back pressure tank 17. The pressure of the reaction system is controlled to 150 psi in combination with the back pressure regulating valve 18 to prevent the solvent in the reaction system from vaporizing;

[0090] (4) The product collected in the product collection tank 16 is a solution containing fluorobenzoic acid. Quantitative analysis using high performance liquid chromatography shows that the yield of fluorobenzoic acid is 88.7%. The solution containing fluorobenzoic acid is subjected to rotary evaporation and purified by a chromatographic column to obtain the final product, fluorobenzoic acid.

[0091] Example 5

[0092] A continuous synthesis method of a halogenated benzoic acid compound, the method is carried out using a continuous synthesis system of a halogenated benzoic acid compound described in Example 1, and the steps are as follows:

[0093] (1) Formic acid and hydrogen peroxide are respectively delivered to the first T-type micro mixer 7 by the first metering pump 4 and the second metering pump 5 for thorough mixing. The mixed materials are then delivered to the magnetically driven active micro mixer 8 together with the halogenated benzaldehyde solution delivered by the third metering pump 6 for mixing to obtain a thoroughly mixed reaction solution.

[0094] The halogenated benzaldehyde solution is a 0.75 mol / L fluorobenzaldehyde solution prepared with ethyl acetate as solvent;

[0095] The rotation speed of the magnetic rotor in the magnetically driven active micromixer 8 is 300 r / min;

[0096] By controlling the flow ratio among the first metering pump 4, the second metering pump 5 and the third metering pump 6, the molar ratio of fluorobenzaldehyde, hydrogen peroxide and formic acid is controlled to be 1.0: 1.2: 12.0;

[0097] (2) The fully mixed reaction liquid enters the magnetically driven oscillating microreactor 11 for oxidation reaction. By adjusting the external magnetic field, the magnetic rotor in the magnetically driven oscillating microreactor 11 is driven to oscillate repeatedly in the microreaction channel, thereby enhancing the transfer characteristics of the reaction system and avoiding the deposition of solid impurities generated during the reaction process. The temperature of the oxidation reaction is controlled by the temperature control device 10 to obtain the reaction liquid after the oxidation reaction.

[0098] The oscillation frequency of the magnetic rotor in the magnetically driven oscillating microreactor 11 is 12 Hz;

[0099] The reaction temperature of the oxidation reaction is 105°C, and the reaction time is controlled to be 22 min by adjusting the flow rates of the first metering pump 4, the second metering pump 5 and the third metering pump 6;

[0100] (3) The reaction liquid after the oxidation reaction flows out from the magnetically driven oscillating microreactor 11, is fully mixed with the ethyl acetate delivered by the fourth metering pump 12 in the second T-type micromixer 13, and then enters the nitrogen back pressure tank 17. The pipeline on the side of the nitrogen back pressure tank 17 is switched alternately by the first stop valve 14 and the second stop valve 15 to achieve product collection while maintaining the stability of the reaction system pressure. The product is collected in the product collection tank 16, and the nitrogen is delivered to the nitrogen back pressure tank 17. The pressure of the reaction system is controlled to 150 psi in combination with the back pressure regulating valve 18 to prevent the solvent in the reaction system from vaporizing;

[0101] (4) The product collected in the product collection tank 16 is a solution containing fluorobenzoic acid. Quantitative analysis using high performance liquid chromatography shows that the yield of fluorobenzoic acid is 89.5%. The solution containing fluorobenzoic acid is subjected to rotary evaporation and purified by a chromatographic column to obtain the final product, fluorobenzoic acid.

[0102] Example 6

[0103] A continuous synthesis method of a halogenated benzoic acid compound, the method is carried out using a continuous synthesis system of a halogenated benzoic acid compound described in Example 1, and the steps are as follows:

[0104] (1) Formic acid and hydrogen peroxide are respectively transported to the first T-type micro mixer 7 by the first metering pump 4 and the second metering pump 5 for thorough mixing. The mixed materials are then transported together with the halogenated benzaldehyde solution transported by the third metering pump 6 into the magnetically driven active micro mixer 8 for mixing to obtain a thoroughly mixed reaction solution.

[0105] The halogenated benzaldehyde solution is a 0.95 mol / L chlorobenzaldehyde solution prepared with ethyl acetate as solvent;

[0106] The rotation speed of the magnetic rotor in the magnetically driven active micromixer 8 is 500 r / min;

[0107] By controlling the flow ratio among the first metering pump 4, the second metering pump 5 and the third metering pump 6, the molar ratio of chlorobenzaldehyde, hydrogen peroxide and formic acid is controlled to be 1.0: 1.1: 8.0;

[0108] (2) The fully mixed reaction liquid enters the magnetically driven oscillating microreactor 11 for oxidation reaction. By adjusting the external magnetic field, the magnetic rotor in the magnetically driven oscillating microreactor 11 is driven to oscillate repeatedly in the microreaction channel, thereby enhancing the transfer characteristics of the reaction system and avoiding the deposition of solid impurities generated during the reaction process. The temperature of the oxidation reaction is controlled by the temperature control device 10 to obtain the reaction liquid after the oxidation reaction.

[0109] The oscillation frequency of the magnetic rotor in the magnetically driven oscillating microreactor 11 is 24 Hz;

[0110] The reaction temperature of the oxidation reaction is 105°C, and the reaction time is controlled to be 22 min by adjusting the flow rates of the first metering pump 4, the second metering pump 5 and the third metering pump 6;

[0111] (3) The reaction liquid after the oxidation reaction flows out from the magnetically driven oscillating microreactor 11, is fully mixed with the ethyl acetate delivered by the fourth metering pump 12 in the second T-type micromixer 13, and then enters the nitrogen back pressure tank 17. The pipeline on the side of the nitrogen back pressure tank 17 is switched alternately by the first stop valve 14 and the second stop valve 15 to achieve product collection while maintaining the stability of the reaction system pressure. The product is collected in the product collection tank 16, and the nitrogen is delivered to the nitrogen back pressure tank 17. The pressure of the reaction system is controlled to 150 psi in combination with the back pressure regulating valve 18 to prevent the solvent in the reaction system from vaporizing;

[0112] (4) The product collected in the product collection tank 16 is a solution containing chlorobenzoic acid. Quantitative analysis using high performance liquid chromatography shows that the yield of chlorobenzoic acid is 91.4%. The solution containing chlorobenzoic acid is subjected to rotary evaporation and purified by a chromatographic column to obtain the final product chlorobenzoic acid.

[0113] Example 7

[0114] A continuous synthesis method of a halogenated benzoic acid compound, the method is carried out using a continuous synthesis system of a halogenated benzoic acid compound described in Example 1, and the steps are as follows:

[0115] (1) Formic acid and hydrogen peroxide are respectively transported to the first T-type micro mixer 7 by the first metering pump 4 and the second metering pump 5 for thorough mixing. The mixed materials are then transported together with the halogenated benzaldehyde solution transported by the third metering pump 6 into the magnetically driven active micro mixer 8 for mixing to obtain a thoroughly mixed reaction solution.

[0116] The halogenated benzaldehyde solution is a 0.95 mol / L bromobenzaldehyde solution prepared with ethyl acetate as solvent;

[0117] The rotation speed of the magnetic rotor in the magnetically driven active micromixer 8 is 500 r / min;

[0118] By controlling the flow ratio among the first metering pump 4, the second metering pump 5 and the third metering pump 6, the molar ratio of bromobenzaldehyde, hydrogen peroxide and formic acid is controlled to be 1.0: 1.1: 8.0;

[0119] (2) The fully mixed reaction liquid enters the magnetically driven oscillating microreactor 11 for oxidation reaction. By adjusting the external magnetic field, the magnetic rotor in the magnetically driven oscillating microreactor 11 is driven to oscillate repeatedly in the microreaction channel, thereby enhancing the transfer characteristics of the reaction system and avoiding the deposition of solid impurities generated during the reaction process. The temperature of the oxidation reaction is controlled by the temperature control device 10 to obtain the reaction liquid after the oxidation reaction.

[0120] The oscillation frequency of the magnetic rotor in the magnetically driven oscillating microreactor 11 is 24 Hz;

[0121] The reaction temperature of the oxidation reaction is 105°C, and the reaction time is controlled to be 22 min by adjusting the flow rates of the first metering pump 4, the second metering pump 5 and the third metering pump 6;

[0122] (3) The reaction liquid after the oxidation reaction flows out from the magnetically driven oscillating microreactor 11, is fully mixed with the ethyl acetate delivered by the fourth metering pump 12 in the second T-type micromixer 13, and then enters the nitrogen back pressure tank 17. The pipeline on the side of the nitrogen back pressure tank 17 is switched alternately by the first stop valve 14 and the second stop valve 15 to achieve product collection while maintaining the stability of the reaction system pressure. The product is collected in the product collection tank 16, and the nitrogen is delivered to the nitrogen back pressure tank 17. The pressure of the reaction system is controlled to 150 psi in combination with the back pressure regulating valve 18 to prevent the solvent in the reaction system from vaporizing;

[0123] (4) The product collected in the product collection tank 16 is a solution containing brominated benzoic acid compounds. Quantitative analysis using high performance liquid chromatography shows that the yield of brominated benzoic acid is 90.8%. The solution containing brominated benzoic acid is subjected to rotary evaporation and purified by a chromatographic column to obtain the final product, brominated benzoic acid.

[0124] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and they cannot be used to limit the protection scope of the present invention. Any equivalent transformation or modification made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A continuous synthesis method of halogenated benzoic acid compounds, characterized in that: The method is carried out using a continuous synthesis system of halogenated benzoic acid compounds, and the main components and connection relationships of the continuous synthesis system are as follows: The first metering pump is connected to formic acid and one end inlet of the first T-type micro mixer through pipelines, respectively; the second metering pump is connected to hydrogen peroxide and the other end inlet of the first T-type micro mixer through pipelines, respectively; the outlet of the first T-type micro mixer is connected to the inlet of the magnetically driven active micro mixer through pipelines; the third metering pump is connected to the halogenated benzaldehyde solution and the inlet of the magnetically driven active micro mixer through pipelines, respectively; the halogenated benzaldehyde solution uses ethyl acetate as a solvent; The outlet of the magnetically driven active micro-mixer is connected to the inlet of the magnetically driven oscillating micro-reactor through a pipeline, the outlet of the magnetically driven oscillating micro-reactor is connected to the inlet of one end of the second T-shaped micro-mixer through a pipeline, and a temperature control device is arranged around the magnetically driven oscillating micro-reactor; The fourth metering pump is connected to the inlet of ethyl acetate and the other end of the second T-type micro mixer through pipelines, respectively; the outlet of the second T-type micro mixer is connected to the nitrogen back pressure tank through a pipeline; the nitrogen back pressure tank is connected to the nitrogen through a pipeline; the nitrogen back pressure tank is provided with a pipeline extending from the tank to the outside of the tank and connected to the outside air; a back pressure regulating valve is provided on the pipeline; a pipeline is provided on the side of the nitrogen back pressure tank to collect the product; two stop valves are sequentially provided on the pipeline; The steps of the method are as follows: (1) Formic acid and hydrogen peroxide are respectively delivered to a first T-type micro-mixer by a first metering pump and a second metering pump for thorough mixing. The mixed materials are then delivered to a magnetically driven active micro-mixer together with a halogenated benzaldehyde solution delivered by a third metering pump for mixing to obtain a thoroughly mixed reaction solution. (2) The fully mixed reaction liquid enters a magnetically driven oscillating microreactor for oxidation reaction. The magnetic rotor in the magnetically driven oscillating microreactor is driven to oscillate repeatedly in the microreaction channel by regulating the external magnetic field. The oxidation reaction temperature is controlled by a temperature control device to obtain a reaction liquid after oxidation reaction. The reaction temperature of the oxidation reaction is 80°C to 120°C, and the reaction time is 15 min to 30 min. (3) The reaction liquid after the oxidation reaction flows out of the magnetically driven oscillating microreactor, is fully mixed with the ethyl acetate delivered by the fourth metering pump in the second T-type micromixer, and then enters the nitrogen back pressure tank. The pipeline on the side of the nitrogen back pressure tank is switched alternately by two stop valves to collect the product while maintaining the stability of the system pressure. The nitrogen is delivered to the nitrogen back pressure tank, and the pressure of the reaction system is controlled to 150 psi in combination with the back pressure regulating valve; (4) The collected product is a solution containing halogenated benzoic acid compounds, which is purified to prepare halogenated benzoic acid.

2. A continuous synthesis method of a halogenated benzoic acid compound according to claim 1, characterized in that: The halogenated group in the halogenated benzoic acid compound is at least one of fluorine, chlorine and bromine.

3. A continuous synthesis method of a halogenated benzoic acid compound according to claim 2, characterized in that: The halogenated benzoic acid compound is fluorobenzoic acid, chlorobenzoic acid or bromobenzoic acid.

4. A continuous synthesis method of a halogenated benzoic acid compound according to any one of claims 1 to 3, characterized in that: Formic acid, hydrogen peroxide, halogenated benzaldehyde solution and ethyl acetate were placed in corresponding storage tanks and stored under nitrogen protection.

5. A continuous synthesis method of a halogenated benzoic acid compound according to any one of claims 1 to 3, characterized in that: The purity of nitrogen is 99.999%; nitrogen is placed in a nitrogen cylinder and transported to a nitrogen back pressure tank through a pipeline, and a nitrogen pressure reducing valve is installed on the pipeline.

6. The continuous synthesis method of a halogenated benzoic acid compound according to claim 1, characterized in that: In step (1), the molar concentration of the halogenated benzaldehyde solution is 0.75 mol / L to 1.0 mol / L; the molar ratio of the halogenated benzaldehyde to hydrogen peroxide is 1.0:1.0 to 1.3, and the molar ratio of the halogenated benzaldehyde to formic acid is 1.0:8.0 to 12.

0.

7. A continuous synthesis method of a halogenated benzoic acid compound according to claim 1, characterized in that: In step (1), the rotation speed of the magnetic rotor in the magnetically driven active micromixer is 300 r / min to 700 r / min.

8. The continuous synthesis method of a halogenated benzoic acid compound according to claim 1, characterized in that: In step (2), the oscillation frequency of the magnetic rotor in the magnetically driven oscillating microreactor is 10 Hz to 25 Hz.

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