Continuous preparation process of aminomethylbenzoic acid

Abstract

The invention belongs to the field of chemical preparation, and relates to a continuous preparation process of aminomethylbenzoic acid. The process specifically comprises the following steps: dissolving chloromethyl benzoic acid in an organic solvent / water mixed solvent to form a chloromethyl benzoic acid solution, and pumping the chloromethyl benzoic acid solution by adopting a first pump; liquid ammonia is pumped in through a second pump; the method comprises the following steps: immobilizing a copper-based catalyst loaded on silicon dioxide into a membrane of a microchannel reactor, and preheating the microchannel reactor; and then carrying out continuous ammonolysis reaction, online acidification, continuous extraction, crystallization and drying to obtain aminomethylbenzoic acid. The process has the advantages of few byproducts, high product yield, high purity, easily controllable reaction process, energy conservation, environmental protection, few generated three wastes, high economic benefit and suitability for industrial production.

Description

Technical Field

[0001] The invention belongs to the field of chemical preparation, and in particular relates to a continuous preparation process of aminomethylbenzoic acid. Background Art

[0002] Aminomethylbenzoic acid, chemical name: 4-aminomethylbenzoic acid, also known as antifibrinolytic aromatic acid, is a commonly used procoagulant in clinical practice and the main raw material for the preparation of the hemostatic drug tranexamic acid, with high market demand.

[0003] At present, the preparation methods of tranexamic acid mainly include: (1) cyanide method: using para-cyanobenzoic acid as raw material, this method involves high-risk reaction reduction amination, and requires the use of highly toxic sodium cyanide, and also involves hydrogen reduction reaction with production risks. It also has high requirements for equipment, factory buildings, and the quality of operators, and has great production safety risks; (2) chloromethylbenzoic acid substitution method: using chloromethylbenzoic acid as raw material, the traditional intermittent ammonolysis has the problems of long reaction time, excessive use of liquid ammonia, poor safety, and multiple extraction and desolvation required for post-processing, cumbersome operation, and many by-products. Invention patent 202411648835.8 uses chloromethylbenzoic acid reaction and replaces traditional ammonium carbonate catalyst with calcium hydroxide, but a cold solvent is required in the whole reaction process, and the steps are strictly controlled, which places high demands on equipment and operators; using chloromethylbenzoic acid as raw material and urotropine as catalyst, the production of by-products is reduced by controlling the temperature, but the amount of ammonia water used is large, the wastewater pollution generated is large, and the cost of three wastes treatment is high; (3) 4-[(2-carboxybenzamido)methyl]benzoic acid acidification method: using 4-[(2-carboxybenzamido)methyl]benzoic acid as raw material, hydrolyzing under acidic conditions, the raw material structure is complex and expensive; (4) Acetamide method, invention patent 202110588759.6 uses acetamide as a new nitrogen source for the synthesis of aminomethylbenzoic acid to replace ammonia water, but this method also uses metal hydride as alkaline raw material, the amount used is large, and it is not suitable for industrial production. At present, the most commonly used method in industry is the chloromethylbenzoic acid substitution method, and the reaction principle is as follows:

[0004]

[0005] This reaction is often a batch reaction in a kettle, requiring long raw material contact times and strict control of reaction conditions to suppress by-product formation. This results in poor reaction stability and high operator requirements. Therefore, to reduce by-product formation and improve economic efficiency, exploring a continuous process for the preparation of aminomethylbenzoic acid is an urgent issue. Summary of the Invention

[0006] The technical problem to be solved by the present invention is: in response to the above-mentioned defects, the present invention provides a continuous preparation process of aminomethylbenzoic acid, which has few by-products, high product yield, high purity, easy control of the reaction process, energy saving and environmental protection, less three wastes generated, high economic benefits, and is suitable for industrial production.

[0007] The present invention solves the technical problem by adopting the following technical solution: a continuous preparation process of aminomethylbenzoic acid, comprising the following steps:

[0008] Step S1, raw material preparation: dissolving chloromethylbenzoic acid in an organic solvent / water mixed solvent to form a chloromethylbenzoic acid solution, and pumping it into the solution using a first pump; pumping liquid ammonia into the solution using a second pump; immobilizing a copper-based catalyst supported on silica into a microchannel reactor diaphragm, and preheating the microchannel reactor;

[0009] Step S2, continuous ammonolysis reaction: a first pump pumps a chloromethylbenzoic acid solution from a first input pipe, and a second pump pumps liquid ammonia from a second input pipe. The flow rate of the solution in the first input pipe is 30-100 mL / min, and the flow rate of the liquid ammonia in the second input pipe is 5-15 mL / min. The volume of a single diaphragm of the microchannel reactor is 100 mL, and the microchannel reactor uses four diaphragms.

[0010] Step S3, online acidification: the ammonolysis solution obtained in step S2 is discharged through the discharge pipe and then mixed with dilute sulfuric acid online to neutralize excess ammonia and adjust the pH to 2-3;

[0011] Step S4, continuous extraction: the acidified liquid enters a continuous liquid-liquid extraction system, using ethyl acetate as an extractant to separate the organic phase;

[0012] Step S5, crystallization and drying: the organic phase is concentrated under reduced pressure and then passed into a tubular crystallizer at a continuous crystallization temperature of 5-10°C. After the crystals are precipitated, they are continuously centrifuged and dried.

[0013] The above technical solution realizes continuous ammonolysis through a microchannel reactor, transforming the traditional batch reaction into a continuous reaction. The modular design of the microchannel reactor, combined with a catalyst with a high specific surface area, realizes efficient mass and heat transfer, accurately controls the reaction time, greatly improves the reaction rate, and shortens the reaction time. At the same time, it avoids the product from continuing to react with the raw material to form by-products. A copper-based catalyst supported on silica is used as the reaction catalyst. Cu / SiO2 catalyzes the ammonolysis of the C-Cl bond with a selectivity of over 99%, which reduces the poor raw material stability problem caused by direct contact of alkaline raw materials such as ammonium bicarbonate and calcium hydroxide with chloromethylbenzoic acid or liquid ammonia in the existing technology. In addition, the high catalytic activity of Cu / SiO2 reduces the cost increase and product contamination caused by metal loss during use, and can maintain continuous operation without deactivation, with good economic benefits. Through online acidification, the acidification accuracy of the ammonolysis solution is intelligently controlled to avoid product decomposition caused by local over-acidification. Combined with continuous extraction and crystallization technology, the yield is ≥95% and the purity is ≥99%, making it suitable for industrial production.

[0014] Furthermore, the microchannel reactor has a temperature of 80-120°C and a pressure of 1-3 MPa. Controlling the reaction temperature and pressure of the microchannel reactor effectively avoids the risk of thermal runaway during the reaction and avoids temperature fluctuations caused by reaction exotherm.

[0015] Furthermore, the molar ratio of the chloromethylbenzoic acid to the liquid ammonia is 1:(1.2-1.5).

[0016] By adopting the above technical solution and combining it with a continuous flow microchannel reactor, the amount of liquid ammonia used is greatly reduced compared with the traditional batch reaction. The reduction in the amount of liquid ammonia used is green and environmentally friendly, reducing the amount of sulfuric acid used to neutralize excess ammonia and reducing the generation of wastewater. On the other hand, it improves the utilization rate of raw materials and has good economic benefits.

[0017] Furthermore, the organic solvent is one of tetrahydrofuran and dioxane. Using tetrahydrofuran or dioxane, on the one hand, reduces the solvent's interference with the copper-based catalyst, ensuring the efficiency of the ammonolysis reaction; on the other hand, it can azeotropize with water, promoting mixing and mass transfer between materials in the microchannel reactor and improving reaction efficiency. Furthermore, both solvents are easy to remove, reducing solvent residue during the crystallization stage.

[0018] Furthermore, the volume ratio of the organic solvent to water is (3-5): 1. Reasonable selection of the volumes of the organic solvent and water improves the mass transfer efficiency during subsequent reactions and also reduces the vaporization of liquid ammonia in the microchannel reactor.

[0019] Furthermore, the concentration of the dilute sulfuric acid used in step S3 is 0.1-0.5M.

[0020] Furthermore, the operation of immobilizing the copper-based catalyst of silica into the diaphragm of the microchannel reactor is as follows: step S0, catalyst immobilization, using hydrogen peroxide to clean the inner wall of the microchannel, tetraethyl orthosilicate (TEOS), ethanol, water and hydrochloric acid are mixed and stirred to form a uniform sol, the sol is injected into the microchannel, statically impregnated to form a uniform film on the inner wall of the channel, and then copper nitrate solution is injected into the microchannel coated with SiO2, allowed to stand, heated to remove the solvent, and hydrogen is introduced for reduction to form a copper-based catalyst loaded on silica.

[0021] By adopting the above technical solution, the microchannel surface is treated with hydrogen peroxide to increase the hydroxyl density on the inner surface, improve the adhesion ability of the sol, and avoid film shedding during the reaction process; the ethyl orthosilicate sol forms a silicon dioxide film on the surface of the microchannel with a uniform pore size distribution. Compared with the impregnation method in the existing technology, the specific surface area is increased, and the three-dimensional structure can highly disperse the copper particles, thereby increasing the contact area between the raw material and the catalyst; this immobilization process is stable and reliable, and the catalyst replacement cycle is greatly extended, making it suitable for industrial production.

[0022] Furthermore, the thickness of the sol uniformly formed film on the inner wall of the channel is 10-50 μm.

[0023] Furthermore, the copper particles in the copper-based catalyst supported on silica have a particle size of 10-50 nm and a loading amount of 5-10 wt%.

[0024] Furthermore, the volume ratio of ethyl orthosilicate, ethanol, water, and hydrochloric acid (37% concentrated hydrochloric acid) is 1:4:2:0.01. Controlling the volume ratio of each system ensures the fluidity of the sol, maintains a corrugated surface structure during subsequent static impregnation, increases the fluid turbulence coefficient, and improves the subsequent mass transfer efficiency between chloromethylbenzoic acid and liquid ammonia.

[0025] The beneficial effects of the present invention are:

[0026] 1. Continuous ammonolysis is achieved through a microchannel reactor, changing the traditional batch reaction into a continuous reaction, greatly shortening the reaction time and avoiding the continued reaction of the product with the raw material to generate by-products. A copper-based catalyst supported on silica is used as the reaction catalyst. Cu / SiO2 catalyzes the ammonolysis of the C-Cl bond with a selectivity of over 99%, reducing the problem of poor raw material stability caused by direct contact of alkaline raw materials such as ammonium bicarbonate and calcium hydroxide with chloromethylbenzoic acid or liquid ammonia in the existing technology. In addition, Cu / SiO2 has high catalytic activity and can maintain continuous operation without deactivation, resulting in good economic benefits.

[0027] 2. Combined with continuous extraction and crystallization technology, the yield is ≥95% and the purity is ≥99%, which is suitable for industrial production.

[0028] 3. Through continuous automatic control, the solvent can be recycled and the recovery rate is ≥98%. DETAILED DESCRIPTION

[0029] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0030] Example 1

[0031] A continuous preparation process of aminomethylbenzoic acid comprises the following steps:

[0032] Step S0, catalyst immobilization, using hydrogen peroxide to clean the inner wall of the microchannel, tetraethyl orthosilicate (TEOS), ethanol, water and hydrochloric acid in a volume ratio of 1:4:2:0.01 are mixed and stirred to form a uniform sol, the sol is injected into the microchannel, static impregnation is performed, so that the sol is uniformly formed on the inner wall of the channel, and the thickness of the sol uniformly formed on the inner wall of the channel is 10 μm, and then copper nitrate solution is injected into the microchannel coated with SiO2, and the solution is allowed to stand, the temperature is increased to remove the solvent, and hydrogen is introduced for reduction to form a copper-based catalyst supported on silica, wherein the copper particles in the copper-based catalyst supported on silica have a particle size of 10 nm and a loading amount of 5 wt%;

[0033] Step S1, raw material preparation: 500 g of chloromethyl benzoic acid is dissolved in 560 mL of a mixed solvent made of dioxane / water, wherein the volume ratio of dioxane to water is 3:1, to form a chloromethyl benzoic acid solution, which is pumped in using a first pump; 100 mL of liquid ammonia is pumped in using a second pump; the microchannel reactor is preheated to a temperature of 80° C.

[0034] Step S2, continuous ammonolysis reaction: a first pump pumps chloromethylbenzoic acid solution from the first input pipe, and a second pump pumps liquid ammonia from the second input pipe. The flow rate of the solution in the first input pipe is 56 mL / min, and the flow rate of liquid ammonia in the second input pipe is 10 mL / min; the volume of a single diaphragm of the microchannel reactor is 100 mL, and the microchannel reactor uses 4 diaphragms; the temperature of the microchannel reactor is 80°C and the pressure is 2.5 MPa.

[0035] Step S3, online acidification: the ammonium solution obtained in step S2 is discharged through the discharge pipe and then mixed online with 0.5M dilute sulfuric acid to neutralize excess ammonia and adjust the pH to 2;

[0036] Step S4, continuous extraction: the acidified liquid enters a continuous liquid-liquid extraction system, using ethyl acetate as an extractant to separate the organic phase;

[0037] Step S5, crystallization and drying: The organic phase was concentrated under reduced pressure and then passed into a tubular crystallizer at a continuous crystallization temperature of 5-10°C. After the crystals were precipitated, they were continuously centrifuged and dried to obtain 438.4 g of the target product, aminobenzoic acid, with a yield of 95.6% and a product purity of 99.5%.

[0038] Example 2

[0039] A continuous preparation process of aminomethylbenzoic acid comprises the following steps:

[0040] Step S0, catalyst immobilization, using hydrogen peroxide to clean the inner wall of the microchannel, tetraethyl orthosilicate (TEOS), ethanol, water and hydrochloric acid in a volume ratio of 1:4:2:0.01 are mixed and stirred to form a uniform sol, the sol is injected into the microchannel, static impregnation is performed, so that the sol is uniformly formed on the inner wall of the channel, and the thickness of the sol uniformly formed on the inner wall of the channel is 50 μm, and then copper nitrate solution is injected into the microchannel coated with SiO2, and the solution is allowed to stand, the temperature is increased to remove the solvent, and hydrogen is introduced for reduction to form a copper-based catalyst supported on silica, wherein the copper particles in the copper-based catalyst supported on silica have a particle size of 45 nm and a loading amount of 10 wt%;

[0041] Step S1, raw material preparation: 500 g of chloromethyl benzoic acid is dissolved in 650 mL of a mixed solvent made of tetrahydrofuran and water, with a volume ratio of tetrahydrofuran to water being 5:1, to form a chloromethyl benzoic acid solution, which is pumped in using a first pump; 120 mL of liquid ammonia is pumped in using a second pump; and a microchannel reactor is preheated to a temperature of 120° C.

[0042] Step S2, continuous ammonolysis reaction: a first pump pumps chloromethylbenzoic acid solution from the first input pipe, and a second pump pumps liquid ammonia from the second input pipe. The flow rate of the solution in the first input pipe is 82 mL / min, and the flow rate of the liquid ammonia in the second input pipe is 15 mL / min; the volume of a single diaphragm of the microchannel reactor is 100 mL, and the microchannel reactor uses 4 diaphragms; the temperature of the microchannel reactor is 120°C and the pressure is 3 MPa.

[0043] Step S3, online acidification: the ammonium solution obtained in step S2 is discharged through the discharge pipe and then mixed online with 0.25M dilute sulfuric acid to neutralize excess ammonia and adjust the pH to 3;

[0044] Step S4, continuous extraction: the acidified liquid enters a continuous liquid-liquid extraction system, using ethyl acetate as an extractant to separate the organic phase;

[0045] Step S5, crystallization and drying: The organic phase was concentrated under reduced pressure and then passed into a tubular crystallizer at a continuous crystallization temperature of 5-10°C. After the crystals were precipitated, they were continuously centrifuged and dried to obtain 441.1 g of the target product, aminomethylbenzoic acid, with a yield of 96.2% and a product purity of 99.5%.

[0046] Example 3

[0047] A continuous preparation process of aminomethylbenzoic acid comprises the following steps:

[0048] Step S0, catalyst immobilization, using hydrogen peroxide to clean the inner wall of the microchannel, tetraethyl orthosilicate (TEOS), ethanol, water and hydrochloric acid in a volume ratio of 1:4:2:0.01 are mixed and stirred to form a uniform sol, the sol is injected into the microchannel, and static impregnation is performed to form a uniform film of the sol on the inner wall of the channel, and the thickness of the uniform film of the sol on the inner wall of the channel is 25 μm, and then a copper nitrate solution is injected into the microchannel coated with SiO2, and the solution is allowed to stand, the temperature is increased to remove the solvent, and hydrogen is introduced for reduction to form a copper-based catalyst supported on silica, wherein the copper particles in the copper-based catalyst supported on silica have a particle size of 25 nm and a loading amount of 8 wt%;

[0049] Step S1, raw material preparation: 500 g of chloromethyl benzoic acid is dissolved in 600 mL of a mixed solvent made of tetrahydrofuran / water, where the volume ratio of tetrahydrofuran to water is 4:1, to form a chloromethyl benzoic acid solution, which is pumped in using a first pump; 100 mL of liquid ammonia is pumped in using a second pump; and a microchannel reactor is preheated to a temperature of 100° C.

[0050] Step S2, continuous ammonolysis reaction: a first pump pumps chloromethylbenzoic acid solution from the first input pipe, and a second pump pumps liquid ammonia from the second input pipe. The flow rate of the solution in the first input pipe is 30 mL / min, and the flow rate of liquid ammonia in the second input pipe is 5 mL / min; the volume of a single diaphragm of the microchannel reactor is 100 mL, and the microchannel reactor uses 4 diaphragms; the temperature of the microchannel reactor is 100°C and the pressure is 1.2 MPa.

[0051] Step S3, online acidification: the ammonium solution obtained in step S2 is discharged through the discharge pipe and then mixed online with 0.1M dilute sulfuric acid to neutralize excess ammonia and adjust the pH to 2.4;

[0052] Step S4, continuous extraction: the acidified liquid enters a continuous liquid-liquid extraction system, using ethyl acetate as an extractant to separate the organic phase;

[0053] Step S5, crystallization and drying: The organic phase was concentrated under reduced pressure and then passed into a tubular crystallizer at a continuous crystallization temperature of 5-10°C. After the crystals were precipitated, they were continuously centrifuged and dried to obtain 451.7 g of the target product, aminomethylbenzoic acid, with a yield of 98.5% and a product purity of 99.5%.

[0054] Example 4

[0055] A continuous preparation process of aminomethylbenzoic acid comprises the following steps:

[0056] Step S0, catalyst immobilization, using hydrogen peroxide to clean the inner wall of the microchannel, tetraethyl orthosilicate (TEOS), ethanol, water and hydrochloric acid in a volume ratio of 1:4:2:0.01 are mixed and stirred to form a uniform sol, the sol is injected into the microchannel, static impregnation is performed, so that the sol is uniformly formed on the inner wall of the channel, and the thickness of the sol uniformly formed on the inner wall of the channel is 30 μm, and then copper nitrate solution is injected into the microchannel coated with SiO2, and the solution is allowed to stand, the temperature is increased to remove the solvent, and hydrogen is introduced for reduction to form a copper-based catalyst supported on silica, wherein the copper particles in the copper-based catalyst supported on silica have a particle size of 15 nm and a loading amount of 10 wt%;

[0057] Step S1, raw material preparation: 500 g of chloromethyl benzoic acid is dissolved in 600 mL of a mixed solvent made of tetrahydrofuran / water, where the volume ratio of tetrahydrofuran to water is 5:1, to form a chloromethyl benzoic acid solution, which is pumped in using a first pump; 110 mL of liquid ammonia is pumped in using a second pump; and a microchannel reactor is preheated to a temperature of 110° C.

[0058] Step S2, continuous ammonolysis reaction: a first pump pumps chloromethylbenzoic acid solution from the first input pipe, and a second pump pumps liquid ammonia from the second input pipe. The flow rate of the solution in the first input pipe is 55 mL / min, and the flow rate of liquid ammonia in the second input pipe is 10 mL / min; the volume of a single diaphragm of the microchannel reactor is 100 mL, and the microchannel reactor uses 4 diaphragms; the temperature of the microchannel reactor is 110°C and the pressure is 2.0 MPa.

[0059] Step S3, online acidification: the ammonium solution obtained in step S2 is discharged through the discharge pipe and then mixed online with dilute sulfuric acid with a concentration of 0.1-0.5M to neutralize excess ammonia and adjust the pH to 2-3;

[0060] Step S4, continuous extraction: the acidified liquid enters a continuous liquid-liquid extraction system, using ethyl acetate as an extractant to separate the organic phase;

[0061] Step S5, crystallization and drying: The organic phase was concentrated under reduced pressure and then passed into a tubular crystallizer at a continuous crystallization temperature of 5-10°C. After the crystals were precipitated, they were continuously centrifuged and dried to obtain 448.5 g of the target product, aminomethylbenzoic acid, with a yield of 97.8% and a product purity of 99.5%.

[0062] Example 5

[0063] The difference between this embodiment and embodiment 3 is that the catalyst immobilization is not newly prepared, but is continued to be used after the microchannel reactor has been continuously operated for 1000 hours as in embodiment 3. The remaining operating steps remain the same; specifically, they are as follows:

[0064] Step S1, raw material preparation: 500 g of chloromethyl benzoic acid is dissolved in 600 mL of a mixed solvent made of tetrahydrofuran / water, where the volume ratio of tetrahydrofuran to water is 4:1, to form a chloromethyl benzoic acid solution, which is pumped in using a first pump; 100 mL of liquid ammonia is pumped in using a second pump; and a microchannel reactor is preheated to a temperature of 100° C.

[0065] Step S2, continuous ammonolysis reaction: a first pump pumps chloromethylbenzoic acid solution from the first input pipe, and a second pump pumps liquid ammonia from the second input pipe. The flow rate of the solution in the first input pipe is 30 mL / min, and the flow rate of liquid ammonia in the second input pipe is 5 mL / min; the volume of a single diaphragm of the microchannel reactor is 100 mL, and the microchannel reactor uses 4 diaphragms; the temperature of the microchannel reactor is 100°C and the pressure is 1.2 MPa.

[0066] Step S3, online acidification: the ammonium solution obtained in step S2 is discharged through the discharge pipe and then mixed online with 0.1M dilute sulfuric acid to neutralize excess ammonia and adjust the pH to 2.4;

[0067] Step S4, continuous extraction: the acidified liquid enters a continuous liquid-liquid extraction system, using ethyl acetate as an extractant to separate the organic phase;

[0068] Step S5, crystallization and drying: The organic phase was concentrated under reduced pressure and then passed into a tubular crystallizer at a continuous crystallization temperature of 5-10°C. After the crystals were precipitated, they were continuously centrifuged and dried to obtain 446.2 g of the target product, aminobenzoic acid, with a yield of 97.3% and a product purity of 99.5%.

[0069] It can be seen from this example that the catalyst immobilized in the microchannel reactor still maintains a high catalytic activity after continuous operation for 1000 hours.

[0070] The continuous preparation process of aminomethylbenzoic acid provided by the present invention realizes continuous ammonolysis through a microchannel reactor, converts a traditional batch reaction into a continuous reaction, greatly shortens the reaction time, and avoids the product and the raw material from continuing to react to generate by-products. A copper-based catalyst supported on silica is used as a reaction catalyst. Cu / SiO2 catalyzes the ammonolysis of the C-Cl bond, and the selectivity can be as high as over 99%. This reduces the problem of poor raw material stability caused by direct contact of alkaline raw materials such as ammonium bicarbonate and calcium hydroxide with chloromethylbenzoic acid or liquid ammonia in the prior art. In addition, the Cu / SiO2 has high catalytic activity, can maintain continuous operation without deactivation, and has good economic benefits. Combined with continuous extraction and crystallization technology, the process has a yield of ≥95% and a purity of ≥99%, making it suitable for industrial production.

[0071] With the above-mentioned ideal embodiment of the present invention as inspiration, and through the above description, relevant personnel can make various changes and modifications without departing from the scope of the technical concept of this invention patent. The technical scope of this invention patent is not limited to the content of the specification, but must be determined according to the scope of the claims.

Claims

1. A continuous process for preparing aminomethylbenzoic acid, comprising the following steps: Step S1, raw material preparation: dissolving chloromethylbenzoic acid in an organic solvent / water mixed solvent to form a chloromethylbenzoic acid solution, and pumping it into the solution using a first pump; pumping liquid ammonia into the solution using a second pump; immobilizing a copper-based catalyst supported on silica into a microchannel reactor diaphragm, and preheating the microchannel reactor; Step S2, continuous ammonolysis reaction: a first pump pumps a chloromethylbenzoic acid solution from a first input pipe, and a second pump pumps liquid ammonia from a second input pipe. The flow rate of the solution in the first input pipe is 30-100 mL / min, and the flow rate of the liquid ammonia in the second input pipe is 5-15 mL / min. The volume of a single diaphragm of the microchannel reactor is 100 mL, and the microchannel reactor uses four diaphragms. Step S3, online acidification: the ammonolysis solution obtained in step S2 is discharged through the discharge pipe and then mixed with dilute sulfuric acid online to neutralize excess ammonia and adjust the pH to 2-3; Step S4, continuous extraction: the acidified liquid enters a continuous liquid-liquid extraction system, using ethyl acetate as an extractant to separate the organic phase; Step S5, crystallization and drying: the organic phase is concentrated under reduced pressure and then passed into a tubular crystallizer at a continuous crystallization temperature of 5-10°C. After the crystals are precipitated, they are continuously centrifuged and dried.

2. A continuous process for preparing aminomethylbenzoic acid according to claim 1, characterized in that: The microchannel reactor has a temperature of 80-120° C. and a pressure of 1-3 MPa.

3. A continuous process for preparing aminomethylbenzoic acid according to claim 1, characterized in that: The molar ratio of the chloromethylbenzoic acid to the liquid ammonia is 1:(1.2-1.5).

4. A continuous process for preparing aminomethylbenzoic acid according to claim 1, characterized in that: The organic solvent is one of tetrahydrofuran and dioxane.

5. A continuous process for preparing aminomethylbenzoic acid according to claim 1, characterized in that: The volume ratio of the organic solvent to water is (3-5):

1.

6. A continuous process for preparing aminomethylbenzoic acid according to claim 1, characterized in that: The concentration of the dilute sulfuric acid used in step S3 is 0.1-0.5M.

7. A continuous preparation process for aminomethylbenzoic acid according to claim 1, characterized in that: The operation of immobilizing the copper-based silica catalyst into the diaphragm of the microchannel reactor is as follows: step S0, catalyst immobilization, using hydrogen peroxide to clean the inner wall of the microchannel, tetraethyl orthosilicate (TEOS), ethanol, water and hydrochloric acid, stirring to form a uniform sol, injecting the sol into the microchannel, statically impregnating to form a uniform film of the sol on the inner wall of the channel, then injecting a copper nitrate solution into the microchannel coated with SiO2, standing, heating to remove the solvent, and introducing hydrogen for reduction to form a copper-based catalyst loaded on silica.

8. A continuous preparation process for aminomethylbenzoic acid according to claim 7, characterized in that: The thickness of the sol uniformly formed film on the inner wall of the channel is 10-50 μm.

9. A continuous process for preparing aminomethylbenzoic acid according to claim 7, characterized in that: The copper particles in the copper-based catalyst supported on silica have a particle size of 10-50 nm and a loading amount of 5-10 wt%.

10. The continuous preparation process of aminomethylbenzoic acid according to claim 7, characterized in that: The volume ratio of the tetraethyl orthosilicate, ethanol, water and hydrochloric acid is 1:4:2:0.01.

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