Continuous preparation method and continuous preparation device of 2-bromo-4-fluoroaniline

Abstract

The invention discloses a continuous preparation method and a continuous preparation device of 2-bromo-4-fluoroaniline, and relates to the technical field of fine chemical engineering. The preparation method comprises the following steps: S1, mixing fluorobenzene with a nitration reagent, and carrying out continuous nitration reaction to obtain a crude product containing 4-fluoronitrobenzene; s2, mixing the crude product containing 4-fluoronitrobenzene with an organic solvent, and carrying out continuous catalytic hydrogenation reaction under the action of a reduction catalyst to obtain a solution containing 4-fluoroaniline; and S3, mixing the solution containing 4-fluoroaniline with a bromination reagent, and carrying out a continuous bromination reaction to obtain a product system containing 2-bromo-4-fluoroaniline, so that continuous preparation of 2-bromo-4-fluoroaniline can be realized, generation of by-products can be reduced, and raw materials can be converted to the greatest extent, thereby improving the purity and yield of 2-bromo-4-fluoroaniline.

Description

Technical Field

[0001] The invention relates to the technical field of fine chemicals, and in particular to a continuous preparation method and a continuous preparation device for 2-bromo-4-fluoroaniline. Background Art

[0002] Bixafen has the characteristics of high efficiency, broad spectrum, long-lasting effect, strong selectivity, etc. It can inhibit spore germination, mycelial growth and spore formation, and is widely used in disease prevention and control of various crops such as fruit trees, vegetables, and grains. The production process of bixafen includes: 2-bromo-4-fluoroaniline and 3-difluoromethyl-1-methyl-1H pyrazole-4-yl chloride undergo substitution reaction, and then Suzuki coupling with 3.4-dichlorophenylboronic acid under palladium catalysis conditions to obtain the target product bixafen, wherein 2-bromo-4-fluoroaniline is the key raw material for preparing bixafen, and its purity will directly affect the production efficiency of bixafen. At present, 2-bromo-4-fluoroaniline is mainly prepared by reducing and brominating 4-fluoronitrobenzene, however, the reduction product 4-fluoroaniline is easy to deteriorate and produce by-products under high temperature environment or light, resulting in changes in the properties of the substance, affecting the yield of 2-bromo-4-fluoroaniline. Summary of the invention

[0003] The main purpose of the present invention is to provide a continuous preparation method and a continuous preparation device for 2-bromo-4-fluoroaniline, so as to solve the problems of many by-products and low yield in the preparation of 2-bromo-4-fluoroaniline in the prior art.

[0004] In order to achieve the above object, according to one aspect of the present invention, a continuous preparation method of 2-bromo-4-fluoroaniline is provided, comprising the following steps:

[0005] S1, mixing fluorobenzene with a nitrating agent to perform a continuous nitration reaction to obtain a crude product containing 4-fluoronitrobenzene;

[0006] S2, mixing the crude product containing 4-fluoronitrobenzene with an organic solvent, and performing a continuous catalytic hydrogenation reaction under the action of a reducing catalyst to obtain a solution containing 4-fluoroaniline;

[0007] S3, mixing the solution containing 4-fluoroaniline with a brominating agent to perform a continuous bromination reaction to obtain a product system including 2-bromo-4-fluoroaniline.

[0008] Further, S1 comprises: pre-cooling fluorobenzene and a nitrating agent independently and then mixing them, so that they undergo a continuous nitration reaction under the action of an acid catalyst to obtain a nitration product;

[0009] The nitration product is subjected to a first quenching to obtain a first quenching product;

[0010] Performing a first extraction and separation on the first quenched product to obtain a first organic phase and a first aqueous phase;

[0011] The first organic phase is subjected to water washing treatment to be neutralized to obtain a water-washed product;

[0012] The washed product is first concentrated to a mass content of 4-fluoronitrobenzene of 90-95%, thereby obtaining a crude product containing 4-fluoronitrobenzene;

[0013] Wherein, the nitrating agent includes concentrated nitric acid, and the mass concentration of the concentrated nitric acid is 50% to 98%;

[0014] The acid catalyst includes at least one of concentrated sulfuric acid, acetic acid, acetic anhydride, acetic acid, acetic anhydride, trifluoroacetic acid, and trifluoroacetic anhydride; and / or,

[0015] The first precooling temperature is -15~-5°C and the time is 5~10min; and / or,

[0016] The temperature of the continuous nitration reaction is -5~10°C and the time is 5~30min; and / or,

[0017] The quenching liquid used in the first quenching is water; and / or,

[0018] The extractant used in the first extraction fraction includes at least one of dichloromethane, ethyl acetate and chloroform; and / or,

[0019] The temperature of the first concentration is 50~70°C and the time is 0.5~3h.

[0020] Furthermore, S2 includes:

[0021] The crude product containing 4-fluoronitrobenzene is mixed with an organic solvent, and then subjected to a second precooling, and then subjected to a continuous catalytic hydrogenation reaction under the action of a reducing catalyst to obtain a hydrogenated product;

[0022] The hydrogenated product is first concentrated to a mass content of 4-fluoroaniline of 90-95%, thereby obtaining a solution containing 4-fluoroaniline; and / or,

[0023] The second precooling temperature is 5-15°C and the time is 5-10 minutes; and / or,

[0024] The reduction catalyst comprises a skeleton and a metal carrier supported on the skeleton, the skeleton is made of at least one of carbon and silicon, and the metal carrier comprises at least one of platinum, palladium and nickel; and / or,

[0025] The temperature of the continuous catalytic hydrogenation reaction is 20-35°C and the time is 10-100 min; and / or,

[0026] The second concentration includes: at a temperature of 50-70° C. and a vacuum degree of 0.1 MPa, spreading the hydrogenation product into a liquid film of uniform thickness, evaporating the organic solvent in the liquid film until the mass content of 4-fluoroaniline is 90-95%, thereby obtaining a solution containing 4-fluoroaniline.

[0027] Furthermore, S3 includes:

[0028] The solution containing 4-fluoroaniline is pre-cooled for a third time and then mixed with a brominating agent to perform a continuous bromination reaction to obtain a brominated product;

[0029] The brominated product is subjected to a second quenching to obtain a second quenched product;

[0030] The second quenched product is subjected to a second extraction and liquid separation to obtain a second organic phase and a second aqueous phase;

[0031] The second organic phase is concentrated for the third time to a 2-bromo-4-fluoroaniline content of 90-95%, to obtain a third concentrated product;

[0032] performing a first drying on the third concentrated product to obtain a product system including 2-bromo-4-fluoroaniline; and / or,

[0033] The third precooling temperature is 5-15°C and the time is 5-10 minutes; and / or,

[0034] The temperature of the continuous bromination reaction is 20-35°C and the time is 5-60 minutes; and / or,

[0035] The quenching liquid used in the second quenching is water; and / or,

[0036] The extractant used in the second extraction fraction is ethyl acetate; and / or,

[0037] The first drying temperature is 40~50℃ and the time is 1~3h.

[0038] Further, the mass ratio of fluorobenzene to concentrated nitric acid is 1:(1.1-1.3); and / or,

[0039] The mass ratio of fluorobenzene to the acid catalyst is 1:(3-5); and / or,

[0040] The mass ratio of 4-fluoronitrobenzene to the organic solvent is 1:(1-20); and / or,

[0041] The mass ratio of 4-fluoronitrobenzene to the reduction catalyst is 1:(0.001~0.01); and / or,

[0042] The organic solvent includes at least one of tetrahydrofuran, acetic acid, ethyl acetate, methanol, ethanol, and N,N-dimethylformamide; and / or,

[0043] The molar ratio of 4-fluoroaniline to the bromination reagent is 1:(0.5-1.2); and / or,

[0044] The bromination reagent includes at least one of bromine, N-bromosuccinimide, and dibromohydantoin; and / or,

[0045] The mass fraction of concentrated nitric acid is 50-68%); and / or,

[0046] The mass fraction of concentrated sulfuric acid is 90~98%.

[0047] Furthermore, in the product system, the mass content of 2-bromo-4-fluoroaniline is 96-98%.

[0048] The second aspect of the present invention provides a continuous preparation device for 2-bromo-4-fluoroaniline, which is used to perform the continuous preparation method provided in the first aspect; the continuous preparation device comprises:

[0049] A nitration reaction unit, used for continuously nitrating a first reaction raw material including fluorobenzene and a nitrating agent to obtain a crude product containing 4-fluoronitrobenzene;

[0050] A hydrogenation reaction unit, used for continuously catalytically hydrogenating a crude product containing 4-fluoronitrobenzene and a second reaction raw material of an organic solvent under the action of a reduction catalyst to obtain a solution containing 4-fluoroaniline;

[0051] A bromination reaction unit, used for continuously brominating a third reaction raw material including a solution containing 4-fluoroaniline and a brominating agent to obtain a product system including 2-bromo-4-fluoroaniline;

[0052] The nitration reaction unit, the hydrogenation reaction unit and the bromination reaction unit are connected in sequence.

[0053] Further, the nitrification reaction unit comprises:

[0054] A first raw material supply unit, used for continuously passing the first reaction raw material into the first continuous reactor;

[0055] A first quenching liquid supply unit, used for providing a first quenching liquid;

[0056] A first continuous reactor comprises a first reaction raw material feed port and a nitration product discharge port, wherein the first reaction raw material feed port is connected to a first raw material supply unit, and the first continuous reactor is used to perform a continuous nitration reaction on the first reaction raw material to obtain a nitration product;

[0057] A first quenching unit comprises a nitration product feed port, a first quenching liquid feed port and a first quenching product discharge port, the nitration product feed port is connected to the nitration product discharge port of the first continuous reactor, the first quenching liquid feed port is connected to the first quenching liquid supply unit, and the first quenching unit is used to perform a first quenching on the nitration product to obtain a first quenching product;

[0058] A first liquid separation unit comprises a first quenched product feed port, a first organic phase discharge port and a first aqueous phase discharge port, wherein the first quenched product feed port is connected to the first quenched product discharge port of the first quenching unit, and the first liquid separation unit is used to perform a first extraction and liquid separation on the first quenched product to obtain a first organic phase and a first aqueous phase;

[0059] A water washing unit, comprising a first organic phase feed port and a water washing product discharge port, wherein the first organic phase feed port is connected to the first organic phase discharge port of the first liquid separation unit, and the water washing unit is used to wash the first organic phase with water to obtain a water washing product;

[0060] A first concentration unit includes a water-washed product feed port and a 4-fluoronitrobenzene discharge port, wherein the water-washed product feed port is connected to the water-washed product discharge port of the water-washing unit, and the first concentration unit is used to perform a first concentration on the water-washed product to obtain a crude product containing 4-fluoronitrobenzene;

[0061] The feed rate of the first reaction raw material is 0.8-1.2 g / min; and / or,

[0062] The first continuous reactor is a tubular reactor, and the number thereof is 1 to 3.

[0063] Further, the hydrogenation reaction unit comprises:

[0064] a second raw material supply unit, used for continuously passing the organic solvent into the second precooler;

[0065] a third raw material supply unit, used for continuously passing hydrogen into the second continuous reactor;

[0066] The second precooler comprises a 4-fluoronitrobenzene feed port, an organic solvent feed port and a second precooling product discharge port, the 4-fluoronitrobenzene feed port is connected to the 4-fluoronitrobenzene discharge port in the nitration reaction unit, the second raw material feed port is connected to the second raw material supply unit, and the second precooler is used to continuously perform a second precooling on the second reaction raw material;

[0067] The second continuous reactor comprises a second precooling product feed port, a third raw material feed port and a hydrogenation product discharge port, wherein the second precooling product feed port is connected to the second precooling product discharge port of the second precooler, and the third raw material feed port is connected to the third raw material supply unit, and the second continuous reactor is used to carry out a continuous hydrogenation reaction between the second precooling product and hydrogen under the action of a catalyst to obtain a hydrogenation product;

[0068] A second concentration unit, comprising a hydrogenation product feed port and a second concentrated product discharge port, wherein the hydrogenation product feed port is connected to the hydrogenation product discharge port of the second continuous reactor, and the second concentration unit is used for performing a second concentration on the hydrogenation product to obtain a solution containing 4-fluoroaniline;

[0069] The feed rate of the second reaction raw material is 1.8-2.2 g / min; and / or,

[0070] The second continuous reactor is a fixed bed hydrogenation reactor loaded with a catalyst.

[0071] Further, the bromination reaction unit comprises:

[0072] a fourth raw material supply unit, used for continuously passing the bromination reagent into the third continuous reactor;

[0073] A second quenching liquid supply unit, used for providing a second quenching liquid;

[0074] A third precooler, comprising a first concentrated product feed port and a third precooled product discharge port, wherein the first concentrated product feed port is connected to the first concentrated product discharge port in the hydrogenation reaction unit, and the third precooler is used to continuously perform a third precooling on the first concentrated product;

[0075] A third continuous reactor comprises a third precooling product feed port, a fourth raw material feed port and a bromination product discharge port, wherein the third precooling product feed port is connected to the third precooling product discharge port of the third precooler, and the fourth raw material feed port is connected to the fourth raw material supply unit, and the third continuous reactor is used to continuously brominate the third reaction raw material to obtain a bromination product;

[0076] A second quenching unit comprises a bromination product feed port, a second quenching liquid feed port and a second quenching product discharge port, wherein the bromination product feed port is connected to the bromination product discharge port of the third continuous reactor, the second quenching liquid feed port is connected to the second quenching liquid supply unit, and the second quenching unit is used to perform a second quenching on the bromination product to obtain a second quenching product;

[0077] A second liquid separation unit comprises a second quenched product feed port, a second organic phase discharge port and a second aqueous phase discharge port, the second quenched product feed port is connected to the second quenched product discharge port of the second quenching unit, and the second liquid separation unit is used to perform a second extraction and liquid separation on the second quenched product to obtain a second organic phase and a second aqueous phase;

[0078] A third concentration unit comprises a second organic phase feed port and a third concentrated product discharge port, wherein the second organic phase feed port is connected to the second organic phase discharge port of the second liquid separation unit, and the third concentration unit is used to perform a third concentration on the second organic phase to obtain a third concentrated product;

[0079] A first drying unit, comprising a third concentrated product feed port and a first dried product discharge port, wherein the third concentrated product feed port is connected to a third concentrated product discharge port of the third concentrated unit, and the first drying unit is used to perform a first drying on the third concentrated product to obtain a product system comprising 2-bromo-4-fluoroaniline;

[0080] The feed rate of the third reaction raw material is 2.2-2.5 g / min; and / or,

[0081] The third continuous reactor is a tubular reactor, the number of which is 1 to 3; and / or,

[0082] The outer sides of the first continuous reactor, the second continuous reactor and the third continuous reactor are all provided with jackets, and the outer walls of the first continuous reactor, the second continuous reactor and the third continuous reactor and the inner walls of their respective corresponding jackets form cavities, and the cavities are used for circulating heat medium; and / or,

[0083] The heat medium is silicone heat-conducting oil; and / or,

[0084] The continuous preparation device also includes a condenser including a gas phase inlet, and the condenser is used to condense the gas phase generated by the first concentration, the second concentration, and the first drying;

[0085] The first concentration unit, the second concentration unit, the third concentration unit and the first drying unit all include a gas phase outlet, and the gas phase outlets are independently connected to the gas phase inlet of the condenser.

[0086] By applying the technical scheme of the present invention, fluorobenzene, a nitrating agent and the like are used as raw materials, a continuous nitration reaction, a continuous catalytic hydrogenation reaction and a continuous bromination reaction are sequentially carried out to realize the continuous preparation of 2-bromo-4-fluoroaniline, avoid the decomposition and deterioration of the intermediate product 4-fluoroaniline, reduce the generation of by-products, and enable the raw materials to be converted to the greatest extent, thereby improving the purity and yield of 2-bromo-4-fluoroaniline. BRIEF DESCRIPTION OF THE DRAWINGS

[0087] Figure 1 This is a diagram of a continuous preparation device for 2-bromo-4-fluoroaniline in one embodiment of the present invention.

[0088] Description of reference numerals:

[0089] A-nitration reaction unit; 1-first raw material supply unit; 1A-fluorobenzene supply unit; 1B-concentrated nitric acid supply unit; 1C-acid catalyst supply unit; 2A-first quenching liquid supply unit; 3-first continuous reactor; 4-first quenching unit; 5-first liquid separation unit; 6-water washing unit; 7-first concentration unit; B-hydrogenation reaction unit; 8-second raw material supply unit; 9-third raw material supply unit; 10-second precooler; 11-second continuous reactor; 12-second concentration unit; 13-storage tank; C-bromination reaction unit; 2B-second quenching liquid supply unit; 14-fourth raw material supply unit; 15-third precooler; 16-third continuous reactor; 17-second quenching unit; 18-second liquid separation unit; 19-third concentration unit; 20-first drying unit; 21-condenser. DETAILED DESCRIPTION

[0090] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0091] As described in the background of the present invention, the preparation of 2-bromo-4-fluoroaniline in the prior art has the problems of low raw material utilization, many by-products and low yield. In order to solve the above problems, the first aspect of the present invention provides a continuous preparation method of 2-bromo-4-fluoroaniline, comprising the following steps:

[0092] S1, mixing fluorobenzene with a nitrating agent to perform a continuous nitration reaction to obtain a crude product containing 4-fluoronitrobenzene;

[0093] S2, mixing the crude product containing 4-fluoronitrobenzene with an organic solvent, and performing a continuous catalytic hydrogenation reaction under the action of a reducing catalyst to obtain a solution containing 4-fluoroaniline;

[0094] S3, mixing the solution containing 4-fluoroaniline with a brominating agent to perform a continuous bromination reaction to obtain a product system including 2-bromo-4-fluoroaniline.

[0095] It should be noted that the chemical formula of fluorobenzene is shown in Formula 1, the chemical formula of 4-fluoronitrobenzene is shown in Formula 2, the chemical formula of 4-fluoroaniline is shown in Formula 3, and the chemical formula of 2-bromo-4-fluoroaniline is shown in Formula 4.

[0096]

[0097] Formula 1 Formula 2

[0098]

[0099] Formula 3 Formula 4

[0100] The continuous preparation method of 2-bromo-4-fluoroaniline of the present invention can be implemented by using a continuous preparation device, and it is sufficient to ensure that the raw materials flow continuously through the continuous reactor.

[0101] Specifically, in S1, in the continuous preparation method of 2-bromo-4-fluoroaniline of the present invention, fluorobenzene (C 6 H 5 F) as a raw material, and reacting it with a nitrating agent such as concentrated nitric acid (HNO 3 ) to carry out a continuous nitration reaction. In the continuous nitration reaction, the hydrogen atoms on the aromatic ring of fluorobenzene are replaced by nitro groups (-NO 2 ) to generate 4-fluoronitrobenzene. The chemical equation of the reaction is: 6 H 5 F + HNO 3 = C 6 H 4 (NO 2 )F + H 2 O, this reaction usually needs to be carried out in the presence of an acid catalyst (such as concentrated sulfuric acid) to increase the reaction rate and yield.

[0102] In S2, the crude product containing 4-fluoronitrobenzene is mixed with an organic solvent to dissolve it, thereby forming a solution containing 4-fluoronitrobenzene. Under the action of a reduction catalyst, hydrogen molecules (H 2 ) is activated, and the nitro group (-NO 2 ) reaction, reducing it to an amino group (-NH 2 ), a solution containing 4-fluoroaniline is obtained. The chemical equation for this reaction can be expressed as: C 6 H 4 (NO 2 )F + 3H 2 =C 6 H 4 F(NH 2 ) + 2H 2 O.

[0103] In S3, the solution containing 4-fluoroaniline is mixed with a brominating agent. Since the amine group is a strong electron-donating group, it can increase the electron density of the benzene ring, making the benzene ring in 4-fluoroaniline more easily attacked by the electrophilic agent. The brominating agent can act as an electrophilic agent to attack the benzene ring of 4-fluoroaniline, causing a substitution reaction, so that the 4-fluoroaniline in the solution containing 4-fluoroaniline and the brominating agent undergo a continuous bromination reaction, and finally obtain a product system including 2-bromo-4-fluoroaniline. When the brominating agent is bromine (Br 2), the reaction equation for the substitution reaction between 4-fluoroaniline and the bromination reagent is: C 6 H 4 F(NH 2 ) + Br 2 =C 6 H 3 FBr 2 +HBr.

[0104] Through the above-mentioned continuous nitration reaction, continuous catalytic hydrogenation reaction and continuous bromination reaction carried out in sequence, the continuous preparation of 2-bromo-4-fluoroaniline is achieved, the decomposition and deterioration of the intermediate product 4-fluoroaniline are avoided, the generation of by-products is reduced, the raw materials are converted to the greatest extent, and the purity and yield of 2-bromo-4-fluoroaniline are improved.

[0105] In some embodiments, S1 includes: independently pre-cooling fluorobenzene and a nitrating agent and then mixing them to obtain a first reaction raw material, subjecting the first reaction raw material to a continuous nitration reaction under the action of an acid catalyst to obtain a nitration product; subjecting the nitrating product to a first quenching to obtain a first quenched product; subjecting the first quenched product to a first extraction and separation to obtain a first organic phase and a first aqueous phase; subjecting the first organic phase to a water washing treatment to neutrality to obtain a water-washed product; subjecting the water-washed product to a first concentration to concentrate the water-washed product to a mass content of 4-fluoronitrobenzene of 90-95%, to obtain a crude product containing 4-fluoronitrobenzene.

[0106] Among them, in order to ensure the complete nitration reaction and reduce the formation of by-products, fluorobenzene, nitrating agent and acid catalyst are first pre-cooled respectively, and then mixed to carry out continuous nitration reaction. In this way, it is helpful to increase the reaction rate, reduce the activation energy, increase the activity, improve the reaction selectivity, etc., thereby improving the efficiency of the continuous nitration reaction and the quality of the product. In some preferred embodiments, the temperature of the first pre-cooling is -15~-5°C, such as -15°C, -12°C, -10°C, -8°C, -5°C or any two thereof; the temperature of the continuous nitration reaction is -5~10°C, such as -5°C, 0°C, 5°C, 10°C or any two thereof.

[0107] When the nitration reaction is completed, in order to prevent further reaction, the nitration product is subjected to a first quenching, that is, a quenching liquid is added to the reaction system to terminate the nitration reaction and prevent and reduce the generation of by-products. In some preferred embodiments, the quenching liquid used for the first quenching is water, and the nitration product is added with sufficient water to dilute concentrated nitric acid and concentrated sulfuric acid. Since 4-fluoronitrobenzene has a low solubility in water, it will separate from the water phase, thereby terminating the nitration reaction.

[0108] The first quenched product is subjected to a first extraction and liquid separation, and specifically, an extraction agent can be used for extraction. In some preferred embodiments, the extraction agent used for the first extraction and liquid separation includes at least one of dichloromethane, ethyl acetate, and chloroform, and the extraction agent is mixed with the first quenched product, and then shaken to allow the two phases to fully contact, 4-fluoronitrobenzene will dissolve in the organic phase, and the two phases are allowed to stand until they are separated to obtain a first organic phase and a first aqueous phase.

[0109] The first organic phase is washed with water until it is neutral, and the residual concentrated sulfuric acid and concentrated nitric acid are further removed to obtain a washed product, i.e., an organic phase containing 4-fluoronitrobenzene, which can be directly used in S2. In some preferred embodiments, the washed product is first concentrated to obtain a crude product containing 4-fluoronitrobenzene, and the extractant can be evaporated using a rotary evaporator or a vacuum pump to obtain a crude product containing 4-fluoronitrobenzene. The temperature of the first concentration is 50-70°C, such as 50°C, 55°C, 60°C, 65°C, 70°C, or any two thereof, and the time is 0.5-3h, such as 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, or any two thereof.

[0110] In some embodiments, the nitrating agent includes concentrated nitric acid, and the mass concentration of the concentrated nitric acid is 50% to 98%; the acid catalyst includes at least one of concentrated sulfuric acid, acetic acid, acetic anhydride, acetic acid, acetic anhydride, trifluoroacetic acid, and trifluoroacetic anhydride.

[0111] In some embodiments, S2 includes: mixing a crude product containing 4-fluoronitrobenzene with an organic solvent, and after a second precooling, performing a continuous catalytic hydrogenation reaction under the action of a preheated reduction catalyst to obtain a hydrogenated product; and performing a first concentration on the hydrogenated product to concentrate it to a mass content of 4-fluoroaniline of 90-95%, thereby obtaining a solution containing 4-fluoroaniline.

[0112] Wherein, in order to ensure that the catalytic hydrogenation reaction is complete and reduce the formation of by-products, 4-fluoronitrobenzene is first mixed with an organic solvent, a second precooling is performed, and then the catalytic hydrogenation reaction is performed under the action of a preheated reduction catalyst. Wherein, the preheated catalyst refers to an activated reduction catalyst, which is usually achieved by heating it with hydrogen at a high temperature, so that it helps to increase the reaction rate, reduce the activation energy, increase the activity of the catalyst, improve the reaction selectivity, etc., thereby improving the efficiency of the catalytic hydrogenation reaction and the quality of the product. In some preferred embodiments, the temperature of the second precooling is 5~15°C, such as 5°C, 8°C, 10°C, 12°C, 15°C or the range composed of any two of them, the temperature of the continuous catalytic hydrogenation reaction is 20~35°C, such as 20°C, 25°C, 30°C, 35°C or the range composed of any two of them, and the temperature of the preheated reduction catalyst is 20~35°C, such as 20°C, 25°C, 30°C, 35°C or the range composed of any two of them.

[0113] The hydrogenation product is substantially a solution containing 4-fluoroaniline, and the concentration of 4-fluoroaniline is further increased by concentration. The concentration process can be achieved using a falling film concentration evaporator. In some preferred embodiments, the first concentration includes: at a temperature of 50 to 70°C and a vacuum degree of 0.1 MPa, the hydrogenation product is spread into a liquid film of uniform thickness, and the organic solvent in the liquid film is evaporated until the mass content of 4-fluoroaniline is 90 to 95%, thereby obtaining a solution containing 4-fluoroaniline. The temperature of the first concentration is, for example, 50°C, 55°C, 60°C, 65°C, 70°C, or a range consisting of any two of them.

[0114] In some embodiments, S3 includes: precooling the solution containing 4-fluoroaniline for a third time and then mixing it with a bromination reagent to perform a continuous bromination reaction to obtain a bromination product; quenching the bromination product for a second time to obtain a second quenched product; extracting and separating the second quenched product for a second time to obtain a second organic phase and a second aqueous phase; concentrating the second organic phase for a third time to a mass content of 2-bromo-4-fluoroaniline of 90-95% to obtain a third concentrated product; and drying the third concentrated product for a first time to obtain a product system including 2-bromo-4-fluoroaniline.

[0115] Specifically, in order to ensure that the bromination reaction is complete and reduce the formation of by-products, the solution containing 4-fluoroaniline and the brominating agent are first independently subjected to the third precooling, and then mixed to carry out the bromination reaction. In this way, it is helpful to increase the reaction rate, reduce the activation energy, increase the activity, improve the reaction selectivity, etc., thereby improving the efficiency of the bromination reaction and the quality of the product. In some preferred embodiments, the temperature of the third precooling is 5 to 15°C, such as 5°C, 8°C, 10°C, 12°C, 15°C or the range of any two of them, and the temperature of the continuous bromination reaction is 20 to 35°C, such as 20°C, 25°C, 30°C, 35°C or the range of any two of them.

[0116] When the bromination reaction reaches the expected conversion rate, in order to prevent further reaction, the reaction can be terminated by adding an excess of quenching liquid to the bromination product for a second quenching, that is, by adding a quenching liquid to the reaction system, the bromination reaction is terminated to prevent and reduce the generation of by-products. In some preferred embodiments, the quenching liquid used for the second quenching is water, and the bromination product is added with sufficient water to dilute the bromination reagent, thereby terminating the bromination reaction.

[0117] The second quenched product is subjected to a second extraction liquid separation, and specifically, an extraction agent can be used for extraction. In some preferred embodiments, the extraction agent used for the second extraction liquid separation is ethyl acetate, and the extraction agent is mixed with the second quenched product, and then shaken to make the two phases fully contact, and 2-bromo-4-fluoroaniline will dissolve in the organic phase, and stand until the two phases are separated to obtain a second organic phase and a second aqueous phase. Specifically, the second quenched product is poured into a separatory funnel, and enough water is added to achieve the separation of the second organic phase and the second aqueous phase. The second organic phase contains the desired 2-bromo-4-fluoroaniline, while the second aqueous phase contains unreacted 4-fluoroaniline and bromination reagent.

[0118] The second organic phase is separated from the separatory funnel and washed with an appropriate amount of water to remove any residual moisture and impurities; the washed second organic phase is concentrated by a third concentration, such as a falling film evaporation concentration device, to remove most of the organic solvent, and then the first drying is performed to remove the residual moisture, and finally a product system including 2-bromo-4-fluoroaniline is obtained, wherein the product system contains high-purity 2-bromo-4-fluoroaniline. In some preferred embodiments, the temperature of the first drying is 40-50° C. and the time is 1-3 hours.

[0119] The present invention does not limit the amount of each raw material, which can be adjusted according to actual conditions. In some embodiments, the mass ratio of fluorobenzene to concentrated nitric acid is 1: (1.1~1.3), for example, 1: 1.1, 1: 1.2, 1: 1.3 or a range consisting of any two of them; and / or, the mass ratio of fluorobenzene to the acid catalyst is 1: (3~5), for example, 1: 3, 1: 4, 1: 5 or a range consisting of any two of them; and / or, the mass ratio of 4-fluoronitrobenzene to the organic solvent is 1: (1~20), for example, 1: 1, 1: 5, 1: 10, 1: 15, 1: 20 or a range consisting of any two of them; and / or, the mass ratio of 4-fluoronitrobenzene to the reduction catalyst is 1: (0.001~0.01), for example, 1: 0.001, 1: 0.005, 1: 0.01 or a range consisting of any two of them; and / or, the organic The solvent includes at least one of tetrahydrofuran, acetic acid, ethyl acetate, methanol, ethanol, and N,N-dimethylformamide (DMF); and / or, the molar ratio of 4-fluoroaniline to the brominating agent is 1:(0.5~1.2), for example, 1:0.5, 1:1, 1:1.2 or a range consisting of any two of them; and / or, and / or, the reduction catalyst includes a skeleton and a metal carrier loaded on the skeleton, the material of the skeleton includes at least one of carbon and silicon, and the metal carrier includes at least one of platinum, palladium, and nickel; and / or, the brominating agent includes at least one of bromine, N-bromosuccinimide (NBS), and dibromohydantoin; and / or, the mass content of concentrated nitric acid is 50%~68%; and / or, the acid catalyst is concentrated sulfuric acid, and the mass content of concentrated sulfuric acid is 90%~98%.

[0120] In some embodiments, the mass content of 2-bromo-4-fluoroaniline in the product system is 96-98%.

[0121] According to a second aspect of the present invention, a continuous preparation device for 2-bromo-4-fluoroaniline is provided, which is used to perform the continuous preparation method provided in the first aspect; the continuous preparation device comprises: a nitration reaction unit A, which is used to continuously nitrate a first reaction raw material including fluorobenzene and a nitrating agent to obtain a crude product containing 4-fluoronitrobenzene; a hydrogenation reaction unit, which is used to continuously catalytically hydrogenate a second reaction raw material including the crude product containing 4-fluoronitrobenzene and an organic solvent under the action of a reducing catalyst to obtain a solution containing 4-fluoroaniline; a bromination reaction unit, which is used to continuously brominate a third reaction raw material including a solution containing 4-fluoroaniline and a brominating agent to obtain a product system including 2-bromo-4-fluoroaniline; the nitration reaction unit A, the hydrogenation reaction unit and the bromination reaction unit are sequentially connected.

[0122] In the prior art, 2-bromo-4-fluoroaniline is prepared by traditional intermittent processes. Traditional intermittent processes have more heterogeneous reaction systems, low gas-liquid mass transfer efficiency, and long required reaction time, resulting in decreased reaction effect, reduced yield, and low production efficiency; and nitration, hydrogenation, and bromination reactions are all high-risk reactions, with large and intense reaction heat release, and poor safety and high risk of traditional intermittent process operation, which has great pollution to the environment. The present invention uses a continuous preparation device, which has good heat and mass transfer effects, and the raw materials are passed into the continuous preparation device, which shortens the reaction time, improves production efficiency, effectively avoids the problem of easy deterioration of 4-fluoroaniline, and improves reaction selectivity and product yield. In addition, the continuous reactor has a large specific heat exchange area, which can quickly remove the reaction heat, realize accurate temperature control of the reaction temperature, and reduce risks.

[0123] In some embodiments, the nitration reaction unit A includes: a first raw material supply unit 1, which is used to continuously pass the first reaction raw material into the first continuous reactor; a first quenching liquid supply unit 2A, which is used to provide a first quenching liquid; a first continuous reactor 3, which includes a first reaction raw material feed port and a nitration product discharge port, the first reaction raw material feed port is connected to the first raw material supply unit, and the first continuous reactor 3 is used to make the first reaction raw material undergo a continuous nitration reaction to obtain a nitration product; a first quenching unit 4, which includes a nitration product feed port, a first quenching liquid feed port and a first quenching product discharge port, the nitration product feed port is connected to the nitration product discharge port of the first continuous reactor 3, the first quenching liquid feed port is connected to the first quenching liquid supply unit 2A, and the first quenching unit 4 is used to perform a first quenching on the nitration product to obtain a first quenched product ; A first liquid separation unit 5, comprising a first quenching product feed port, a first organic phase discharge port and a first aqueous phase discharge port, the first quenching product feed port is connected to the first quenching product discharge port of the first quenching unit 4, and the first liquid separation unit 5 is used to perform a first extraction and liquid separation on the first quenching product to obtain a first organic phase and a first aqueous phase; a water washing unit 6, comprising a first organic phase feed port and a water washing product discharge port, the first organic phase feed port is connected to the first organic phase discharge port of the first liquid separation unit 5, and the water washing unit 6 is used to wash the first organic phase to obtain a water washing product; a first concentrating unit 7, comprising a water washing product feed port and a 4-fluoronitrobenzene discharge port, the water washing product feed port is connected to the water washing product discharge port of the water washing unit 6, and the first concentrating unit 7 is used to perform a first concentration on the water washing product to obtain a crude product containing 4-fluoronitrobenzene.

[0124] By controlling the feed rate of the first reaction raw material, the reaction rate can be regulated. In some preferred embodiments, the feed rate of the first reaction raw material is 0.8-1.2 g / min, such as 0.8 g / min, 0.9 g / min, 1 g / min, 1.1 g / min, 1.2 g / min or any two thereof.

[0125] In some preferred embodiments, the first continuous reactor 3 is a tubular reactor, and the number thereof is 1 to 3, which can be adjusted according to actual needs.

[0126] In some preferred embodiments, the first raw material supply unit 1 includes a fluorobenzene supply unit 1A, a concentrated nitric acid supply unit 1B and an acid catalyst supply unit 1C, which are respectively used to provide fluorobenzene, concentrated nitric acid and concentrated sulfuric acid, and the fluorobenzene supply unit 1A, the concentrated nitric acid supply unit 1B and the acid catalyst supply unit 1C are each independently provided with a first temperature control unit, a second temperature control unit and a third temperature control unit, which are used to perform a first precooling on each of them. The discharge ports of the first temperature control unit, the second temperature control unit and the third temperature control unit are respectively connected to the first raw material feed port of the first continuous reactor 3.

[0127] In some embodiments, the hydrogenation reaction unit comprises: a second raw material supply unit 8, for continuously passing the organic solvent into the second precooler 10; a third raw material supply unit 9, for continuously passing hydrogen into the second continuous reactor 11; the second precooler 10 comprises a 4-fluoronitrobenzene feed port, a second raw material feed port and a second precooling product discharge port, The 4-fluoronitrobenzene feed port is connected to the 4-fluoronitrobenzene discharge port in the nitration reaction unit A, the second raw material feed port is connected to the second raw material supply unit 8, and the second precooler 10 is used to continuously perform a second precooling on the crude product and the organic solvent containing 4-fluoronitrobenzene; the second continuous reactor 11 includes a second precooling product feed port, a third raw material feed port and a hydrogenation product discharge port, the second precooling product feed port is connected to the second precooling product discharge port of the second precooler 10, the third raw material feed port is connected to the third raw material supply unit 9, and the second continuous reactor 11 is used to make the second precooling product and hydrogen react continuously under the action of a reducing catalyst to obtain a hydrogenated product; the second concentrating unit 12 includes a hydrogenated product feed port and a first concentrated product discharge port, the hydrogenated product feed port is connected to the hydrogenated product discharge port of the second continuous reactor 11, and the second concentrating unit 12 is used to perform a second concentration on the hydrogenated product to obtain a solution containing 4-fluoroaniline.

[0128] By controlling the feed rate of the second reaction raw material, the reaction rate can be regulated. In some preferred embodiments, the feed rate of the second reaction raw material is 1.8 to 2.2 g / min, such as 1.8 g / min, 1.9 g / min, 2 g / min, 2.1 g / min, 2.2 g / min, or any two thereof.

[0129] The second reactor may be a conventional hydrogenation reactor in the art, for example, a fixed bed hydrogenation reactor or a fluidized bed hydrogenation reactor. In some preferred embodiments, the second reactor is a fixed bed hydrogenation reactor with a reduction catalyst immobilized thereon.

[0130] In some embodiments, the hydrogenation reaction unit further includes a storage tank 13 for storing a solution containing 4-fluoroaniline, and the second concentrated product outlet of the second concentration unit 12 is connected to the second concentrated product feed port of the storage tank 13 .

[0131] In some embodiments, the bromination reaction unit includes: a fourth raw material supply unit 14, which is used to continuously pass the bromination reagent into the third continuous reactor 16; a second quenching liquid supply unit, which is used to provide a second quenching liquid; a third precooler 15, which includes a second concentrated product feed port and a third precooling product outlet, the second concentrated product feed port is connected to the second concentrated product outlet in the hydrogenation reaction unit, and the third precooler 15 is used to continuously perform a third precooling on the second concentrated product; the third continuous reactor 16 includes a third precooling product The third precooling product feed port is connected to the third precooling product discharge port of the third precooler 15, the fourth raw material feed port is connected to the fourth raw material supply unit 14, and the third continuous reactor 16 is used to make the third reaction raw material undergo continuous bromination reaction to obtain a brominated product; the second quenching unit 17 includes a bromination product feed port, a second quenching liquid feed port and a second quenching product discharge port, the bromination product feed port is connected to the bromination product discharge port of the third continuous reactor 16, the second quenching liquid feed port is connected to the bromination product discharge port of the third continuous reactor 16, and the second quenching liquid feed port is connected to the bromination product discharge port of the third continuous reactor 16. The feed port is connected to the second quenching liquid supply unit, and the second quenching unit 17 is used to perform a second quenching on the brominated product to obtain a second quenched product; the second liquid separation unit 18 includes a second quenched product feed port, a second organic phase discharge port and a second aqueous phase discharge port, the second quenched product feed port is connected to the second quenched product discharge port of the second quenching unit 17, and the second liquid separation unit 18 is used to perform a second extraction and liquid separation on the second quenched product to obtain a second organic phase and a second aqueous phase; the third concentration unit 19 includes a second organic phase feed port and a third concentrated product discharge port, the second organic phase feed port is connected to the second organic phase discharge port of the second liquid separation unit 18, and the third concentration unit 19 is used to perform a second concentration on the second organic phase to obtain a third concentrated product; the first drying unit 20 includes a third concentrated product feed port and a first dried product discharge port, the third concentrated product feed port is connected to the third concentrated product discharge port of the third concentration unit 19, and the first drying unit 20 is used to perform a first drying on the third concentrated product to obtain a product system including 2-bromo-4-fluoroaniline.

[0132] By controlling the feed rate of the third reaction raw material, the reaction rate can be regulated. In some preferred embodiments, the feed rate of the third reaction raw material is 2.2-2.5 g / min.

[0133] In some preferred embodiments, the third continuous reactor 16 is a tubular reactor, and the number thereof is 1 to 3, which can be adjusted according to actual needs.

[0134] In order to achieve precise control of the reaction temperature, in some preferred embodiments, the outer sides of the first continuous reactor 3, the second continuous reactor 11, and the third continuous reactor 16 are all provided with jackets, and the outer walls of the first continuous reactor 3, the second continuous reactor 11, and the third continuous reactor 16 form a cavity with the inner walls of their respective corresponding jackets, and the cavity is used for circulating heat medium, and the heat medium is silicone heat transfer oil.

[0135] The first liquid separation unit 5 and the second liquid separation unit 18 contain an extractant for achieving the first extraction liquid separation and the second extraction liquid separation.

[0136] By collecting the organic solvent in the concentration and drying processes, the utilization rate of raw materials can be further improved. In some preferred embodiments, the continuous preparation device also includes a condenser 21, including a gas phase inlet, and the condenser 21 is used to condense the gas phase generated by the first concentration, the second concentration, the third concentration, and the first drying; the first concentration unit 7, the second concentration unit 12, the third concentration unit, and the first drying unit 20 all include a gas phase outlet, and the gas phase outlets are independently connected to the gas phase inlet of the condenser 21; a cold medium flows in the shell side of the condenser 21, and the cold medium is circulating water.

[0137] The present application is further described in detail below in conjunction with specific embodiments. These embodiments should not be construed as limiting the scope of protection claimed in the present application.

[0138] Example 1

[0139] 1. The continuous preparation device of 2-bromo-4-fluoroaniline in this embodiment is as follows Figure 1 As shown, including:

[0140] A nitration reaction unit A is used to continuously perform a nitration reaction on a first reaction raw material including fluorobenzene, concentrated nitric acid and concentrated sulfuric acid to obtain a crude product containing 4-fluoronitrobenzene;

[0141] A hydrogenation reaction unit B is used to continuously catalyze hydrogenation of a second reaction raw material including a crude product containing 4-fluoronitrobenzene and an organic solvent under the action of a reduction catalyst to obtain a solution containing 4-fluoroaniline;

[0142] A bromination reaction unit C is used to continuously brominate a third reaction raw material including a solution containing 4-fluoroaniline and a brominating agent to obtain a product system including 2-bromo-4-fluoroaniline;

[0143] The nitration reaction unit A, the hydrogenation reaction unit B, and the bromination reaction unit C all include continuous reactors connected in sequence;

[0144] Wherein, the nitration reaction unit A comprises:

[0145] The first raw material supply unit 1 is used to continuously pass the first reaction raw material including fluorobenzene, concentrated nitric acid and concentrated sulfuric acid into the nitration reaction unit A; the first raw material supply unit 1 includes a fluorobenzene supply unit 1A, a concentrated nitric acid supply unit 1B, and an acid catalyst supply unit 1C, which are respectively used to continuously pass fluorobenzene, concentrated nitric acid and concentrated sulfuric acid into the nitration reaction unit A; and the fluorobenzene supply unit 1A, the concentrated nitric acid supply unit 1B, and the acid catalyst supply unit 1C are each independently provided with a first temperature control unit, a second temperature control unit, and a third temperature control unit, which are used to perform a first precooling on each of them;

[0146] A first quenching liquid supply unit 2A is used to provide a first quenching liquid, and the first quenching liquid is water;

[0147] The first continuous reactor 3 comprises a first raw material feed port and a nitration product discharge port, and the first raw material feed port is connected to the discharge port of the first raw material supply unit 1; the first continuous reactor is used for performing a continuous nitration reaction on the first reaction raw material after the first precooling to obtain a nitration product; the first continuous reactor 3 is a tubular reactor, and the number is 1 to 3;

[0148] A first quenching unit 4, comprising a nitration product feed port and a first quenching product discharge port, the nitration product feed port is connected to the nitration product discharge port of the first continuous reactor 3 and the first quenching liquid supply unit 2A, and the first quenching unit 4 is used to perform a first quenching on the nitration product to obtain a first quenching product;

[0149] A first liquid separation unit 5, comprising a first quenched product feed port, a first organic phase discharge port and a first aqueous phase discharge port, the first quenched product feed port is connected to the first quenched product discharge port of the first quenching unit 4, and the first liquid separation unit 5 is used to perform a first extraction and liquid separation on the first quenched product to obtain a first organic phase and a first aqueous phase;

[0150] A water washing unit 6, comprising a first organic phase feed port and a water washing product discharge port, wherein the first organic phase feed port is connected to the first organic phase discharge port of the first liquid separation unit 5, and the water washing unit 6 is used to wash the first organic phase with water to obtain a water washing product;

[0151] A first concentration unit 7, comprising a water-washed product feed port and a 4-fluoronitrobenzene discharge port, wherein the water-washed product feed port is connected to the water-washed product discharge port of the water-washing unit 6, and the first concentration unit 7 is used for first concentrating the water-washed product to obtain a crude product containing 4-fluoronitrobenzene;

[0152] The hydrogenation reaction unit B comprises:

[0153] A second raw material supply unit 8, used to continuously pass the organic solvent into the hydrogenation reaction unit B;

[0154] A third raw material supply unit 9, used to continuously pass hydrogen into the hydrogenation reaction unit B;

[0155] The second precooler 10 includes a 4-fluoronitrobenzene feed port, a second raw material feed port and a second precooling product discharge port. The 4-fluoronitrobenzene feed port is connected to the 4-fluoronitrobenzene discharge port in the nitration reaction unit A. The second raw material feed port is connected to the second raw material supply unit 8. The second precooler 10 is used to continuously perform a second precooling on the second reaction raw material.

[0156] The second continuous reactor 11 includes a second precooling product feed port, a third raw material feed port and a hydrogenation product discharge port. The second precooling product feed port is connected to the second precooling product discharge port of the second precooler 10, and the third raw material feed port is connected to the third raw material supply unit 9. The second continuous reactor 11 is used to continuously catalyze the hydrogenation reaction of the second precooling product and hydrogen under the action of a reducing catalyst to obtain a hydrogenation product; the second continuous reactor is a fixed bed hydrogenation reactor loaded with a reducing catalyst;

[0157] The second concentration unit 12 includes a hydrogenation product feed port and a second concentrated product discharge port, the hydrogenation product feed port is connected to the hydrogenation product discharge port of the second continuous reactor 11, and the second concentration unit 12 is used to perform a second concentration on the hydrogenation product to obtain a second concentrated product, i.e., a solution containing 4-fluoroaniline;

[0158] A storage tank 13, comprising a second concentrated product feed port and a 4-fluoroaniline solution discharge port, the second concentrated product feed port is connected to the second concentrated product discharge port of the second concentration unit 12, and the storage tank 13 is used to store a solution containing 4-fluoroaniline;

[0159] Bromination reaction unit C comprises:

[0160] A fourth raw material supply unit 14, used for continuously passing the bromination reagent into the bromination reaction unit C;

[0161] The second quenching liquid supply unit 2B is used to provide the second quenching liquid to the second liquid separation unit 18, and the second quenching liquid is water;

[0162] The third precooler 15 comprises a second concentrated product feed port and a third precooled product discharge port, the second concentrated product feed port is connected to the 4-fluoroaniline solution discharge port in the hydrogenation reaction unit B, and the third precooler 15 is used to continuously perform a third precooling on the third reaction raw material;

[0163] The third continuous reactor 16 includes a third precooling product feed port, a fourth raw material feed port and a bromination product discharge port. The third precooling product feed port is connected to the third precooling product discharge port of the third precooler 15, and the fourth raw material feed port is connected to the fourth raw material supply unit 14. The third continuous reactor 16 is used to continuously brominate the third precooling product and the bromination reagent to obtain a bromination product. The third continuous reactor is a tubular reactor, and the number is 1 to 3;

[0164] The second quenching unit 17 includes a bromination product feed port, a second quenching liquid feed port and a second quenching product discharge port, the bromination product feed port is connected to the bromination product discharge port of the third continuous reactor 16, the second quenching liquid feed port is connected to the second quenching liquid supply unit 2B, and the second quenching unit 17 is used to perform a second quenching on the bromination product to obtain a second quenching product;

[0165] The second liquid separation unit 18 includes a second quenched product feed port, a second organic phase discharge port, and a second aqueous phase discharge port. The second quenched product feed port is connected to the second quenched product discharge port of the second quenching unit 17. The second liquid separation unit 18 is used to perform a second extraction and liquid separation on the second quenched product to obtain a second organic phase and a second aqueous phase.

[0166] The third concentration unit 19 includes a second organic phase feed port and a third concentrated product discharge port, the second organic phase feed port is connected to the second organic phase discharge port of the second liquid separation unit 18, and the third concentration unit 19 is used to perform a third concentration on the second organic phase to obtain a third concentrated product;

[0167] The first drying unit 20 includes a second concentrated product feed port and a first dried product discharge port, the third concentrated product feed port is connected to the third concentrated product discharge port of the third concentrated unit 19, and the first drying unit 20 is used to dry the third concentrated product to obtain a product system including 2-bromo-4-fluoroaniline;

[0168] The condenser 21 includes a gas phase inlet, and the condenser 21 is used to condense the gas phase generated by the first concentration, the second concentration, the third concentration, and the first drying; a cold medium flows in the shell side of the condenser 21, and the cold medium is circulating water;

[0169] The outer sides of the first continuous reactor 3, the second continuous reactor 11, and the third continuous reactor 16 are all provided with jackets, and the outer walls of the first continuous reactor 3, the second continuous reactor 11, and the third continuous reactor 16 and the inner walls of their respective corresponding jackets form cavities, and the cavities are used to circulate heat medium;

[0170] 2. The continuous preparation method of 2-bromo-4-fluoroaniline in this embodiment comprises the following steps:

[0171] S1, fluorobenzene, concentrated nitric acid and concentrated sulfuric acid in a mass ratio of 1:1.2:4 are respectively discharged from their respective supply units, and after a first precooling at -5°C for 5-10 minutes, the first raw material feed port of the first continuous reactor 3 is fed at a feed flow rate of 0.8-1.2 g / min into the first continuous reactor 3 for mixing to form a first reaction raw material, and the first reaction raw material is subjected to a continuous nitration reaction at 0°C for 10-30 minutes to obtain a nitration product; wherein the mass content of concentrated nitric acid is 65%); the mass content of concentrated sulfuric acid is (98%);

[0172] The nitration product is discharged through the nitration product discharge port of the first continuous reactor 3, and enters the first quenching unit 4 through the nitration product feed port of the first quenching unit 4 for first quenching to obtain a first quenched product; the quenching liquid used for the first quenching is water flowing in from the first quenching liquid supply unit 2A;

[0173] The first quenched product is discharged through the first quenched product discharge port of the first quenching unit 4, and enters the first liquid separation unit 5 through the first quenched product feed port of the first liquid separation unit 5 for first extraction and liquid separation to obtain a first organic phase and a first aqueous phase; the extractant used in the first extraction and liquid separation is ethyl dichloroacetate;

[0174] The first organic phase is discharged through the first organic phase discharge port of the first liquid separation unit 5, and enters the water washing unit 6 through the first organic phase feed port of the water washing unit 6 for water washing treatment, and is washed with water to neutrality to obtain an organic phase containing 4-fluoronitrobenzene;

[0175] The organic phase containing 4-fluoronitrobenzene is discharged through the water washing product discharge port of the water washing unit 6, and enters the first concentration unit 7 through the water washing product feed port of the first concentration unit 7 for first concentration to obtain a crude product containing 4-fluoronitrobenzene;

[0176] S2, the crude product containing 4-fluoronitrobenzene is discharged through the 4-fluoronitrobenzene outlet of the first concentration unit 7, and methanol (the amount added satisfies the ratio of methanol solvent mass to 4-fluoronitrobenzene mass of 10 g / g) is discharged through the second raw material supply unit 8, and 4-fluoronitrobenzene and methanol are mixed into the second precooler 10 through the 4-fluoronitrobenzene feed port and the second raw material feed port of the second precooler 10 to form a second reaction raw material. After the second reaction raw material is precooled at 25° C. for 5 to 10 minutes, it is discharged through the second precooling product outlet of the second precooler 10, and the second reaction raw material is fed into the second continuous reactor 11 at a feed rate of 1.8 to 2.2 g / min. The second pre-cooling product feed port enters the second continuous reactor 11, and at the same time, the hydrogen in the third raw material supply unit 9 is discharged through the discharge port, and enters the second continuous reactor 11 through the third raw material feed port of the second continuous reactor 11, so that the second reaction raw material and hydrogen are continuously catalytically hydrogenated for 30 to 100 minutes under the reducing catalyst at 30°C to obtain a hydrogenated product; wherein the mass ratio of 4-fluoronitrobenzene to methanol is 1:10; the mass ratio of 4-fluoronitrobenzene to the reducing catalyst is 1:0.01;

[0177] The hydrogenation product is discharged through the hydrogenation product discharge port of the second continuous reactor 11, and enters the second concentration unit 12 through the hydrogenation product feed port of the second concentration unit 12. Under the conditions of a temperature of 50-70° C. and a vacuum degree of 0.1 MPa, the hydrogenation product is spread into a liquid film of uniform thickness, and the organic solvent in the liquid film is evaporated until the mass content of 4-fluoroaniline is 90-95%, thereby obtaining a solution containing 4-fluoroaniline, which flows into the storage tank 13;

[0178] S3, the solution containing 4-fluoroaniline and bromine are discharged through the 4-fluoroaniline solution discharge port of the storage tank 13 and the discharge port of the fourth raw material supply unit 14 respectively, and enter the third precooler 15 through the first concentrated product feed port and the fourth raw material feed port of the third precooler 15 to mix to form a third reaction raw material, the third reaction raw material is precooled at 10°C for 5-10 minutes, and then discharged through the third precooling product discharge port of the third precooler 15, and the third reaction raw material enters the third continuous reactor 16 through the third precooling product feed port of the third continuous reactor 16 at a feed flow rate of 2.2-2.5 g / min to carry out continuous bromination reaction at 30°C for 5-60 minutes to obtain a brominated product; wherein the molar ratio of 4-fluoroaniline to bromine is 1:1.1; the reduction catalyst comprises a nickel skeleton and palladium supported on the nickel skeleton, and the mass ratio of the nickel skeleton to the palladium is 1:(0.02-0.08);

[0179] The bromination product is discharged through the bromination product discharge port of the third continuous reactor 16, and enters the second quenching unit 17 through the bromination product feed port of the second quenching unit 17 for second quenching to obtain a second quenched product; the quenching liquid used for the second quenching is water flowing in from the second quenching liquid supply unit 2B;

[0180] The second quenched product is discharged through the second quenched product discharge port of the second quenching unit 17, and enters the second liquid separation unit 18 through the second quenched product feed port of the second liquid separation unit 18 for second extraction and liquid separation to obtain a second organic phase and a second aqueous phase; the extractant used for the second extraction and liquid separation is ethyl acetate;

[0181] The second organic phase is discharged through the second organic phase discharge port of the second liquid separation unit 18, and enters the third concentration unit 19 through the second organic phase feed port of the third concentration unit 19. Under the conditions of a temperature of 50-70° C. and a vacuum degree of 0.1 MPa, the second organic phase is spread into a liquid film of uniform thickness, and the organic solvent in the liquid film is evaporated until it is concentrated to (the mass content of 2-bromo-4-fluoroaniline is 90-95%), thereby obtaining a third concentrated product;

[0182] The third concentrated product is discharged through the third concentrated product outlet of the third concentrated unit 19, enters the first drying unit 20 through the third concentrated product feed port of the first drying unit 20, and is dried at 40-50° C., and a product system including 2-bromo-4-fluoroaniline is obtained at the first dried product outlet of the first drying unit 20;

[0183] The gas phase outlets of the first concentration unit 7, the second concentration unit 12, the third concentration unit 19, and the first drying unit 20 are independently connected to the gas phase inlet of the condenser 21, so that the gas phases generated by the first concentration, the second concentration, the third concentration, and the first drying flow into the condenser 21 for condensation treatment to recover the solvent.

[0184] In the product system of Example 1, the mass content of 2-bromo-4-fluoroaniline is 96-98%.

[0185] Example 2

[0186] The difference from Example 1 is that in the continuous preparation S2 of 2-bromo-4-fluoroaniline, methanol is replaced by ethanol.

[0187] Example 3

[0188] The difference from Example 1 is that in the continuous preparation of 2-bromo-4-fluoroaniline S2, methanol is replaced by ethyl acetate.

[0189] Example 4

[0190] The difference from Example 1 is that in the continuous preparation of 2-bromo-4-fluoroaniline S2, methanol is replaced by tetrahydrofuran.

[0191] Example 5

[0192] The difference from Example 1 is that in the continuous preparation of 2-bromo-4-fluoroaniline S2, methanol is replaced by acetic acid.

[0193] Example 6

[0194] The difference from Example 1 is that in the continuous preparation of 2-bromo-4-fluoroaniline S2, methanol is replaced by N,N-dimethylformamide (DMF).

[0195] Example 7

[0196] The difference from Example 1 is that in the continuous preparation of 2-bromo-4-fluoroaniline S3, bromine is replaced by N-bromosuccinimide (NBS).

[0197] Example 8

[0198] The difference from Example 1 is that in the continuous preparation of 2-bromo-4-fluoroaniline S3, bromine is replaced by dibromohydantoin.

[0199] Example 9

[0200] The difference from Example 1 is that in the continuous preparation S1 of 2-bromo-4-fluoroaniline, "fluorobenzene, concentrated nitric acid and concentrated sulfuric acid in a mass ratio of 1:1.2:4" is replaced by "fluorobenzene and concentrated nitric acid in a mass ratio of 1:1.2".

[0201] Example 10

[0202] The difference from Example 1 is that in the continuous preparation S1 of 2-bromo-4-fluoroaniline, "fluorobenzene, concentrated nitric acid and concentrated sulfuric acid in a mass ratio of 1:1.2:4" is replaced by "fluorobenzene, concentrated nitric acid and acetic acid in a mass ratio of 1:1.2:4".

[0203] Embodiment 11

[0204] The difference from Example 1 is that in the continuous preparation S1 of 2-bromo-4-fluoroaniline, "fluorobenzene, concentrated nitric acid and concentrated sulfuric acid in a mass ratio of 1:1.2:4" is replaced by "fluorobenzene, concentrated nitric acid and acetic anhydride in a mass ratio of 1:1.2:4".

[0205] Example 12

[0206] The difference from Example 1 is that in the continuous preparation S1 of 2-bromo-4-fluoroaniline, "fluorobenzene, concentrated nitric acid and concentrated sulfuric acid in a mass ratio of 1:1.2:4" is replaced by "fluorobenzene, concentrated nitric acid and trifluoroacetic acid in a mass ratio of 1:1.2:4".

[0207] Embodiment 13

[0208] The difference from Example 1 is that in the continuous preparation S1 of 2-bromo-4-fluoroaniline, "fluorobenzene, concentrated nitric acid and concentrated sulfuric acid in a mass ratio of 1:1.2:4" is replaced by "fluorobenzene, concentrated nitric acid and trifluoroacetic anhydride in a mass ratio of 1:1.2:4".

[0209] Embodiment 14

[0210] The difference from Example 1 is that in the continuous preparation S1 of 2-bromo-4-fluoroaniline, "fluorobenzene, concentrated nitric acid and concentrated sulfuric acid in a mass ratio of 1:1.2:4" is replaced by "fluorobenzene and fuming nitric acid in a mass ratio of 1:1.2".

[0211] Test example

[0212] 1. Reaction purity

[0213] The analysis was performed using HPLC or GC analytical instruments.

[0214] 2. Yield

[0215] Calculated according to yield = actual production of target product / theoretical production of target product × 100%.

[0216] The test results are shown in Table 1.

[0217] Table 1

[0218]

[0219] Table 2

[0220]

[0221] Table 3

[0222]

[0223] Table 4

[0224]

[0225] According to Table 1 to Table 4, the present invention uses fluorobenzene, nitrating agent, etc. as raw materials, and sequentially carries out nitration, hydrogenation and bromination, and can realize the continuous preparation of 2-bromo-4-fluoroaniline, avoids the decomposition and deterioration of intermediate product 4-fluoroaniline, and reduces the generation of by-products. Further, when the present invention uses fluorobenzene, concentrated nitric acid, concentrated sulfuric acid, etc. as raw materials, sequentially carries out nitration, hydrogenation and bromination, not only can realize the continuous preparation of 2-bromo-4-fluoroaniline, avoids the decomposition and deterioration of intermediate product 4-fluoroaniline, reduces the generation of by-products, and can make raw materials be transformed to the greatest extent, thereby improving the purity and yield of 2-bromo-4-fluoroaniline, further can make the purity of 2-bromo-4-fluoroaniline ≥80%, yield ≥50%. Wherein, the product purity and yield of embodiment 14 are high, but fuming nitric acid is used in the preparation process, a large amount of nitric acid vapor can be released, which is unfavorable for the safety of continuous preparation, and the cost of fuming nitric acid is much higher than concentrated nitric acid.

[0226] The present invention uses a continuous preparation device with good heat and mass transfer effects. The raw materials are introduced into the continuous preparation device, which shortens the reaction time, improves the production efficiency, effectively avoids the problem of easy deterioration of 4-fluoroaniline, and improves the reaction selectivity and product yield. In addition, the continuous reactor has a large specific heat exchange area, can quickly remove the reaction heat, realize accurate temperature control of the reaction temperature, and reduce risks.

[0227] The above description is only a preferred embodiment of the present invention and is 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 preparation method of 2-bromo-4-fluoroaniline, characterized in that: The following steps are involved: S1, mixing fluorobenzene with a nitrating agent to perform a continuous nitration reaction to obtain a crude product containing 4-fluoronitrobenzene; S2, mixing the crude product containing 4-fluoronitrobenzene with an organic solvent, and performing a continuous catalytic hydrogenation reaction under the action of a reducing catalyst to obtain a solution containing 4-fluoroaniline; S3, mixing the solution containing 4-fluoroaniline with a brominating agent to perform a continuous bromination reaction to obtain a product system including 2-bromo-4-fluoroaniline.

2. The continuous preparation method according to claim 1, characterized in that: The S1 includes: The fluorobenzene and the nitrating agent are independently pre-cooled and then mixed to perform a continuous nitration reaction under the action of an acid catalyst to obtain a nitration product; Performing a first quenching on the nitration product to obtain a first quenched product; Performing a first extraction and separation on the first quenched product to obtain a first organic phase and a first aqueous phase; The first organic phase is subjected to water washing treatment, and after being washed to neutrality, a water-washed product is obtained; The washed product is first concentrated to a mass content of 4-fluoronitrobenzene of 90-95%, thereby obtaining a crude product containing 4-fluoronitrobenzene; Wherein, the nitrating agent includes concentrated nitric acid, and the mass concentration of the concentrated nitric acid is 50% to 98%; The acid catalyst comprises at least one of concentrated sulfuric acid, acetic acid, acetic anhydride, acetic acid, acetic anhydride, trifluoroacetic acid, and trifluoroacetic anhydride; and / or, The first precooling temperature is -20 to 0°C and the time is 5 to 10 minutes; and / or, The temperature of the continuous nitration reaction is -10 to 50°C and the time is 10 to 30 minutes; and / or, The first quenching liquid used in the first quenching is water; and / or, The extractant used in the first extraction fraction includes at least one of dichloromethane, ethyl acetate and chloroform; and / or, The temperature of the first concentration is 50-70° C., and the time is 0.5-3 h.

3. The continuous preparation method according to claim 2, characterized in that: The S2 includes: The crude product containing 4-fluoronitrobenzene is mixed with an organic solvent, and after a second precooling, a continuous catalytic hydrogenation reaction is carried out under the action of a reducing catalyst to obtain a hydrogenated product; The hydrogenated product is concentrated for the second time to a mass content of 4-fluoroaniline of 90-95%, thereby obtaining the solution containing 4-fluoroaniline; and / or, The second precooling temperature is 5-15°C and the time is 5-10 min; and / or, The catalyst comprises a skeleton and a metal carrier supported on the skeleton, wherein the skeleton is made of at least one of carbon and silicon, and the metal carrier comprises at least one of platinum, palladium and nickel; and / or, The hydrogenation reaction temperature is 20-35°C and the time is 30-100 min; and / or, The second concentration comprises: evaporating the organic solvent at a temperature of 50-70° C. and a vacuum degree of 0.06-0.1 MPa until the mass content of 4-fluoroaniline is 90-95%, thereby obtaining a solution containing 4-fluoroaniline.

4. The continuous preparation method according to claim 1, characterized in that: The S3 includes: The solution containing 4-fluoroaniline is subjected to a third precooling and then mixed with a brominating agent to perform a continuous bromination reaction to obtain a brominated product; The brominated product is subjected to a second quenching to obtain a second quenched product; The second quenched product is subjected to a second extraction and liquid separation to obtain a second organic phase and a second aqueous phase; The second organic phase is concentrated for a third time to a content of 2-bromo-4-fluoroaniline of 90-95%, thereby obtaining a third concentrated product; The third concentrated product is subjected to a first drying to obtain the product system comprising 2-bromo-4-fluoroaniline; and / or, The third precooling temperature is -5 to 10°C and the time is 5 to 10 min; and / or, The temperature of the continuous bromination reaction is 0-35°C and the time is 5-60 min; and / or, The second quenching liquid used in the second quenching is water; and / or, The extractant used in the second extraction fraction is ethyl acetate; and / or, The first drying process is performed at a temperature of 40-50° C. and a time of 1-3 hours.

5. The continuous preparation method according to claim 2, characterized in that: The mass ratio of the fluorobenzene to the concentrated nitric acid is 1:(1.1-1.3); and / or, The mass ratio of the fluorobenzene to the acid catalyst is 1:(3-5); and / or, The mass ratio of the 4-fluoronitrobenzene to the organic solvent is 1:(1-20); and / or, The mass ratio of the 4-fluoronitrobenzene to the reduction catalyst is 1:(0.001-0.01); and / or, The organic solvent comprises at least one of tetrahydrofuran, acetic acid, ethyl acetate, methanol, ethanol and N,N-dimethylformamide; and / or, The molar ratio of the 4-fluoroaniline to the bromination reagent is 1:(0.5-1.2); and / or, The bromination reagent comprises at least one of bromine, N-bromosuccinimide and dibromohydantoin; and / or, The mass fraction of the concentrated nitric acid is 50-68%; and / or, The acid catalyst is concentrated sulfuric acid, and the mass fraction of the concentrated sulfuric acid is 90-98%.

6. The continuous preparation method according to any one of claims 1 to 5, characterized in that: In the product system, the mass content of 2-bromo-4-fluoroaniline is 96-98%.

7. A continuous preparation device for 2-bromo-4-fluoroaniline, characterized in that: Used to perform the continuous preparation method according to any one of claims 1 to 6; the continuous preparation device comprises: A nitration reaction unit (A) is used to continuously nitrate a first reaction raw material including fluorobenzene and a nitrating agent to obtain a crude product containing 4-fluoronitrobenzene; A hydrogenation reaction unit (B) is used to continuously catalytically hydrogenate a crude product containing 4-fluoronitrobenzene and a second reaction raw material containing an organic solvent under the action of a reducing catalyst to obtain a solution containing 4-fluoroaniline; A bromination reaction unit (C) is used to continuously brominate the third reaction raw material including the solution containing 4-fluoroaniline and the brominating agent to obtain a product system including 2-bromo-4-fluoroaniline; The nitration reaction unit (A), the hydrogenation reaction unit (B), and the bromination reaction unit (C) are connected in sequence.

8. The continuous preparation device according to claim 7, characterized in that: The nitration reaction unit (A) comprises: A first raw material supply unit (1) is used to continuously pass the first reaction raw material into the first continuous reactor (3); A first quenching liquid supply unit (2A), used for providing a first quenching liquid; A first continuous reactor (3), comprising a first reaction raw material feed port and a nitration product discharge port, wherein the first reaction raw material feed port is connected to the first raw material supply unit (1), and the first continuous reactor (3) is used to cause the first reaction raw material to undergo a continuous nitration reaction to obtain a nitration product; a first quenching unit (4), comprising a nitration product feed port, a first quenching liquid feed port and a first quenching product discharge port, the nitration product feed port being connected to the nitration product discharge port of the first continuous reactor (3), the first quenching liquid feed port being connected to the first quenching liquid supply unit (2A), and the first quenching unit (4) being used to perform a first quenching on the nitration product to obtain a first quenching product; A first liquid separation unit (5), comprising a first quenched product feed port, a first organic phase discharge port and a first aqueous phase discharge port, wherein the first quenched product feed port is connected to the first quenched product discharge port of the first quenched product unit (4), and the first liquid separation unit (5) is used to perform a first extraction and liquid separation on the first quenched product to obtain a first organic phase and a first aqueous phase; A water washing unit (6), comprising a first organic phase feed port and a water washing product discharge port, wherein the first organic phase feed port is connected to the first organic phase discharge port of the first liquid separation unit (5), and the water washing unit (6) is used to wash the first organic phase with water to obtain a water washing product; A first concentration unit (7), comprising a water-washed product feed port and a 4-fluoronitrobenzene discharge port, wherein the water-washed product feed port is connected to the water-washed product discharge port of the water-washing unit (6), and the first concentration unit (7) is used to perform a first concentration on the water-washed product to obtain a crude product containing 4-fluoronitrobenzene; The feed rate of the first reaction raw material is 0.8-1.2 g / min; and / or, The first continuous reactor (3) is a tubular reactor, and the number thereof is 1 to 3.

9. The continuous preparation device according to claim 8, characterized in that: The hydrogenation reaction unit (B) comprises: A second raw material supply unit (8) is used to continuously pass the organic solvent into the second precooler (10); a third raw material supply unit (9), used for continuously passing hydrogen into the second continuous reactor (11); A second precooler (10) comprises a 4-fluoronitrobenzene feed port, an organic solvent feed port and a second precooling product discharge port, wherein the 4-fluoronitrobenzene feed port is connected to the 4-fluoronitrobenzene discharge port in the nitration reaction unit (A), and the organic solvent feed port is connected to the second raw material supply unit (8). The second precooler (10) is used to continuously perform a second precooling on the second reaction raw material; The second continuous reactor (11) comprises a second precooling product feed port, a third raw material feed port and a hydrogenation product discharge port, wherein the second precooling product feed port is connected to the second precooling product discharge port of the second precooler (10), and the third raw material feed port is connected to the third raw material supply unit (9). The second continuous reactor (11) is used to carry out a continuous catalytic hydrogenation reaction between the second precooling product and hydrogen under the action of a reducing catalyst to obtain a hydrogenation product; A second concentration unit (12), comprising a hydrogenation product feed port and a second concentrated product discharge port, wherein the hydrogenation product feed port is connected to the hydrogenation product discharge port of the second continuous reactor (11), and the second concentration unit (12) is used to perform a second concentration on the hydrogenation product to obtain a solution containing 4-fluoroaniline; The feed rate of the second reaction raw material is 1.8-2.2 g / min; and / or, The second continuous reactor (11) is a fixed bed hydrogenation reactor loaded with a reduction catalyst.

10. The continuous preparation device according to claim 9, characterized in that: The bromination reaction unit (C) comprises: a fourth raw material supply unit (14), used for continuously introducing the bromination reagent into the third continuous reactor (16); A second quenching liquid supply unit (2B), used for providing a second quenching liquid; a third precooler (15), comprising a first concentrated product feed port and a third precooled product discharge port, wherein the first concentrated product feed port is connected to the first concentrated product discharge port in the hydrogenation reaction unit (B), and the third precooler (15) is used to continuously perform a third precooling on the first concentrated product; a third continuous reactor (16), comprising a third precooling product feed port, a brominating agent feed port and a bromination product discharge port, wherein the third precooling product feed port is connected to the third precooling product discharge port of the third precooler (15), and the brominating agent feed port is connected to the fourth raw material supply unit (14), and the third continuous reactor (16) is used to cause the third reaction raw material to undergo a continuous bromination reaction to obtain a bromination product; A second quenching unit (17), comprising a bromination product feed port, a second quenching liquid feed port and a second quenching product discharge port, wherein the bromination product feed port is connected to the bromination product discharge port of the third continuous reactor (16), the second quenching liquid feed port is connected to the second quenching liquid supply unit (2B), and the second quenching unit (17) is used to perform a second quenching on the bromination product to obtain a second quenching product; A second liquid separation unit (18), comprising a second quenched product feed port, a second organic phase discharge port and a second aqueous phase discharge port, wherein the second quenched product feed port is connected to the second quenched product discharge port of the second quenched product unit (17), and the second liquid separation unit (18) is used to perform a second extraction and liquid separation on the second quenched product to obtain a second organic phase and a second aqueous phase; A third concentration unit (19), comprising a second organic phase feed port and a second concentrated product discharge port, wherein the second organic phase feed port is connected to the second organic phase discharge port of the second liquid separation unit (18), and the third concentration unit (19) is used to perform a third concentration on the second organic phase to obtain a third concentrated product; a first drying unit (20), comprising a third concentrated product feed port and a first dried product discharge port, the third concentrated product feed port being connected to the third concentrated product discharge port of the third concentrated unit (19), the first drying unit (20) being used for performing a first drying on the third concentrated product to obtain a product system comprising 2-bromo-4-fluoroaniline; The feed rate of the third reaction raw material is 2.2-2.5 g / min; and / or, The third continuous reactor (16) is a tubular reactor, the number of which is 1 to 3; and / or, The outer sides of the first continuous reactor (3), the second continuous reactor (11), and the third continuous reactor (16) are all provided with jackets, and the outer walls of the first continuous reactor (3), the second continuous reactor (11), and the third continuous reactor (16) and the inner walls of the jackets corresponding to them form cavities, and the cavities are used for circulating heat medium; and / or, The heat medium is silicone heat-conducting oil; and / or, The continuous preparation device further comprises a condenser (21) comprising a gas phase inlet, and the condenser (21) is used to condense the gas phase generated by the first concentration, the second concentration, the third concentration, and the first drying; The first concentration unit (7), the second concentration unit (12), the third concentration unit (19), and the first drying unit (20) all comprise gas phase outlets, and the gas phase outlets are each independently connected to the gas phase inlet of the condenser (21).

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