Preparation method and reaction device of fluoboric acid diazonium salt

Abstract

The invention relates to a preparation method and a reaction device of fluoboric acid diazonium salt, the preparation method comprises the following steps: (1) a first reaction material is introduced into a first microchannel reactor for a diazotization reaction to obtain a first reacted material, and the first reaction material comprises an o-fluoroaniline hydrochloride solution and a nitrite solution; and (2) introducing a fluoboric acid solution and the first reaction post-material into a second microchannel reactor, and carrying out a salt forming reaction to obtain a second reaction post-material containing fluoboric acid diazonium salt. The micro-channel reactor is used for carrying out diazotization reaction and salt forming reaction, and the diazotization reaction and the salt forming reaction can be accurately controlled, so that the reaction stability is improved, and a high-purity product is obtained.

Description

Technical Field

[0001] The present invention relates to the technical field of fluoborate diazonium salt synthesis, and particularly relates to a preparation method and a reaction device for fluoborate diazonium salt. Background Art

[0002] Fluoborate diazonium salt is an intermediate for synthesizing o-difluorobenzene, and o-difluorobenzene is the initial raw material for synthesizing the chiral cyclopropylamine intermediate of ticagrelor. The current production process of o-difluorobenzene includes highly hazardous reactions such as diazotization and catalytic hydrogenation. Among them, the diazotization reaction is a strongly exothermic reaction, and the formed diazonium salt has poor thermal stability, is prone to decomposition, and has potential explosion hazards. The current mainstream production process is batch reaction operation, and the reaction temperature needs to be strictly controlled during the reaction to avoid irreversible self-coupling reactions, decomposition reactions, etc. At present, the process used in the industrial production of o-difluorobenzene products does not have quality and cost advantages and cannot meet the requirements of green chemistry.

[0003] CN119504340A discloses a preparation method for polyfluoro-substituted benzene series compounds based on diazonium salts. Using o-fluoroaniline, fluoboric acid, and sodium nitrite as raw materials, after reacting at a reaction temperature below 10°C for 2 - 4 hours, filtration and purification are carried out to obtain the diazonium salt intermediate. Specifically: before the reaction, first cool o-fluoroaniline to 4 - 6°C and then slowly dropwise add fluoboric acid, and keep the temperature of the obtained mixture below 10°C and stir for 0.5 h; then slowly dropwise add sodium nitrite and keep the temperature of the mixture below 10°C. The operation of filtration and purification is to obtain a filter cake after filtering the reaction solution, wash the filter cake with absolute ethanol 1 - 2 times, and then carry out vacuum drying of the filter cake at 50°C to obtain the diazonium salt intermediate. Its yield is 76.1 - 95.0%, with a relatively large variation range and unstable reaction.

[0004] In summary, it is necessary to develop a preparation method for fluoborate diazonium salt to improve the stability of the reaction, greatly improve the safety and reliability of the o-difluorobenzene production process, and obtain high-purity products. Summary of the Invention

[0005] To solve the above technical problems, the present invention provides a preparation method for continuously synthesizing fluoborate diazonium salt. By using a microchannel reactor for diazotization reaction and salt formation reaction, the temperature of the reaction system is precisely controlled to precisely control the diazotization reaction and salt formation reaction, improve the stability of the reaction, and obtain high-purity products.

[0006] To achieve this purpose, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a preparation method for fluoborate diazonium salt, and the preparation method includes the following steps:

[0008] (1) Introduce the first reaction material into the first microchannel reactor for diazotization reaction to obtain the first post-reaction material. The first reaction material includes o-fluoroaniline hydrochloride solution and nitrite solution;

[0009] (2) Introduce the fluoboric acid solution and the first post-reaction material into the second microchannel reactor for salt formation reaction to obtain the second post-reaction material containing fluoboric acid diazonium salt.

[0010] The equation for the diazotization reaction is:

[0011]

[0012] The equation for the salt formation reaction is:

[0013]

[0014] In the present invention, first, o-fluoroaniline hydrochloride solution and nitrite solution are introduced into the first microchannel reactor for diazotization reaction to generate the first post-reaction material. The reaction liquid can quickly and evenly contact and mix in this process. This step can be completed in an extremely short time. Using the first microchannel reactor can well control both the mixing of reactants and the temperature of the reaction system. Then, the first post-reaction material is mixed with fluoboric acid solution and introduced into the second microchannel reactor for salt formation reaction to prepare fluoboric acid diazonium salt. Due to the high specific surface area and strong turbulence effect of the microchannel reactor, the reaction liquid can be quickly mixed in this process, avoiding the problems of possible local reaction and uneven reaction.

[0015] The first post-reaction material includes: aromatic amine, nitrite, aryl diazonium salt, N2, biphenyl, and aryl halide.

[0016] The second post-reaction material includes: o-fluorobenzenediazonium fluoborate, nitrite, fluoboric acid, and ammonia, where the molecular weight of fluoboric acid diazonium salt is 209.92.

[0017] The present invention first uses an o-fluoroaniline hydrochloride solution and nitrite for a diazotization reaction, and then undergoes a salting reaction with fluoboric acid, which can improve the stability of the diazonium salt, avoid decomposition, and can improve the purity of the product. The intermediate generated during the diazotization of aromatic amines is very active and may lead to side reactions. That is, performing the diazotization reaction first and then the salting reaction can convert the diazonium salt into the final product more quickly, thereby effectively controlling the generation of by-products. This process can increase the conversion rate of the reaction. If the o-fluoroaniline hydrochloride solution first undergoes a salting reaction with fluoboric acid and then a diazotization reaction with nitrite, it will affect the stability of the fluoroborate. Fluoboric acid diazonium salts are generally relatively stable under acidic conditions, but if the salting process is carried out first, the subsequent diazotization process will cause the decomposition or incomplete reaction of the fluoroborate due to changes in acidity and temperature, and it will also increase the difficulty of process control, thereby reducing the conversion rate of the reaction.

[0018] As a preferred technical solution of the present invention, the first microchannel reactor and the second microchannel reactor each independently include a first heat exchange medium layer, a reaction material layer, and a second heat exchange medium layer arranged in sequence from the inside out; the first reaction material is introduced into the reaction material layer of the first microchannel reactor, and the first heat exchange medium is independently introduced into the first heat exchange medium layer and the second heat exchange medium layer of the first microchannel reactor.

[0019] Both the diazotization reaction and the salting reaction in the present invention are exothermic reactions. Among them, the reaction enthalpy of the diazotization reaction is -138 kJ / mol. At the same time, both the diazotization reaction and the salting reaction of the present invention need to be carried out at low temperature. Therefore, the reaction temperature needs to be strictly controlled. The microchannel reactor used in the present invention has a double-tube structure, and its inner, middle, and outer three-layer structures respectively correspond to the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer. The present invention introduces the reaction material into the middle layer of the microchannel reactor, and heat exchange medium layers are respectively arranged on the inner side and the outer side of the reaction material. The heat exchange medium is used to perform convective heat transfer on the reaction material on the inner side and the outer side of the reaction material respectively, which can increase the heat transfer effect to control the reaction temperature.

[0020] Preferably, the first heat exchange medium in the first heat exchange medium layer and the second heat exchange medium layer of the first microchannel reactor forms a turbulent flow.

[0021] As described above, the heat of reaction in the diazotization reaction and the salt formation reaction involved in the present invention is very large, and the entire reaction process has high requirements for temperature control. When the heat of reaction cannot be transferred in time, the occurrence of side reactions will increase, and high-purity diazonium fluoroborate cannot be prepared. In the first microchannel reactor of the present invention, the flow state of the heat exchange medium is turbulent flow. Compared with plug flow, turbulent flow can disrupt the thermal boundary layer, reduce the thermal resistance, significantly improve the heat transfer efficiency, and at the same time make the temperature distribution of the heat exchange medium more uniform, avoiding local overheating or overcooling to affect the heat exchange effect on the reaction materials. Further, turbulent flow can increase the heat exchange efficiency for the reaction materials by reducing the flow dead zone and avoiding local retention.

[0022] Preferably, the flow rate of the first heat exchange medium is 10-30 mL / min, for example, it can be 10 mL / min, 15 mL / min, 20 mL / min, 25 mL / min or 30 mL / min, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable.

[0023] Preferably, the temperature of the first heat exchange medium is -20 to 0 °C, for example, it can be -20 °C, -15 °C, -10 °C, -5 °C or 0 °C, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable.

[0024] Preferably, the residence time of the first reaction material in the first microchannel reactor is 5-10 s, for example, it can be 5 s, 6 s, 7 s, 8 s, 9 s or 10 s, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable.

[0025] In the present invention, the first reaction material only needs to stay in the first microchannel reactor for 5-10 s to complete the diazotization reaction. Using a microchannel reactor for the diazotization reaction in the present invention can shorten the reaction time and improve the reaction efficiency.

[0026] Preferably, the fluoroboric acid solution and the first post-reaction material are introduced into the reaction material layer of the second microchannel reactor, and the second heat exchange medium is independently introduced into the first heat exchange medium layer and the second heat exchange medium layer of the second microchannel reactor.

[0027] Preferably, the second heat exchange medium in the first heat exchange medium layer and the second heat exchange medium layer of the second microchannel reactor forms a turbulent flow.

[0028] In the second microchannel reactor of the present invention, the flow state of the heat exchange medium is turbulent flow, which can improve the heat exchange efficiency of the salt formation reaction to obtain a high-purity product.

[0029] Preferably, the flow rate of the second heat exchange medium is 20 to 50 mL / min, for example, it can be 20 mL / min, 25 mL / min, 30 mL / min, 35 mL / min, 40 mL / min, 45 mL / min or 50 mL / min, but is not limited to the listed values, and other unlisted values within the above value range are equally applicable.

[0030] Preferably, the temperature of the second heat exchange medium is -30 to -10 °C, for example, it can be -30 °C, -25 °C, -20 °C, -15 °C or -10 °C, but is not limited to the listed values, and other unlisted values within the above value range are equally applicable.

[0031] Preferably, the first heat exchange medium and the second heat exchange medium independently include any one or at least two combinations of ethylene glycol, propylene glycol or brine solution. Among them, typical but non-limiting combinations include: the combination of ethylene glycol and propylene glycol, the combination of propylene glycol and brine solution, the combination of ethylene glycol and brine solution, and the combination of ethylene glycol, propylene glycol and brine solution.

[0032] Preferably, the residence time of the fluoboric acid solution and the first reaction product in the second microchannel reactor is 8 to 15 s, for example, it can be 8 s, 9 s, 10 s, 11 s, 12 s, 13 s, 14 s or 15 s, but is not limited to the listed values, and other unlisted values within the above value range are equally applicable.

[0033] In the present invention, the fluoboric acid and the first reaction product only need to stay in the second microchannel reactor for 8 - 15 s to complete the salt-forming reaction. Using the microchannel reactor for the salt-forming reaction in the present invention can shorten the reaction time and improve the reaction efficiency.

[0034] As a preferred technical solution of the present invention, the preparation method of the o-fluoroaniline hydrochloride includes: mixing a hydrochloric acid solution and o-fluoroaniline, heating to complete dissolution, and then cooling to a predetermined temperature to obtain the o-fluoroaniline hydrochloride solution.

[0035] Preferably, the heating temperature is 30 to 80 °C, for example, it can be 30 °C, 40 °C, 45 °C, 50 °C, 60 °C, 70 °C or 80 °C, but is not limited to the listed values, and other unlisted values within the above value range are equally applicable, preferably 40 to 50 °C.

[0036] Preferably, the mass fraction of hydrochloric acid in the hydrochloric acid solution is 30 to 38%, for example, it can be 30%, 32%, 34%, 36% or 38%, but is not limited to the listed values, and other unlisted values within the above value range are equally applicable.

[0037] Preferably, the molar ratio of hydrochloric acid to o-fluoroaniline in the hydrochloric acid solution is (1.0 - 2.4):1. For example, it can be 1.0:1, 1.2:1, 1.4:1, 1.6:1, 1.8:1, 2.0:1, 2.2:1 or 2.4:1. However, it is not limited to the listed values, and other unlisted values within the above numerical range are equally applicable. Preferably, it is (1.4 - 2.0):1.

[0038] Preferably, the predetermined temperature is -15 to 5°C. For example, it can be -15°C, -10°C, -5°C, 0°C or -5°C. However, it is not limited to the listed values, and other unlisted values within the above numerical range are equally applicable.

[0039] In the present invention, the hydrochloric acid solution and o-fluoroaniline are mixed by stirring. The mixing process should be carried out at a relatively low temperature. After the addition of the materials is completed, heating is carried out to promote the complete dissolution of the materials, and then it is cooled to the predetermined temperature for reaction to prepare an o-fluoroaniline hydrochloride solution.

[0040] As a preferred technical solution of the present invention, the temperature of the first reaction material is -10 to 20°C. For example, it can be -10°C, -5°C, 0°C, 5°C, 10°C, 15°C or 20°C. However, it is not limited to the listed values, and other unlisted values within the above numerical range are equally applicable. Preferably, it is -5 to 5°C.

[0041] Preferably, the temperature of the diazotization reaction is -5 to 35°C. For example, it can be -5°C, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C or 35°C. However, it is not limited to the listed values, and other unlisted values within the above numerical range are equally applicable. Preferably, it is 0 to 20°C.

[0042] It can be seen from the temperature limited by the diazotization reaction that its suitable temperature range is relatively narrow. Under the condition of a large reaction heat, the reaction temperature is extremely likely to fluctuate. Therefore, it is necessary to strictly control the temperature during the reaction process to reduce the occurrence of side reactions during the reaction and improve the purity of the final product. At the same time, the diazotization reaction is carried out under low-temperature conditions, which can avoid side reactions that may occur during diazotization, thus ensuring the selectivity of the reaction.

[0043] Preferably, the nitrite in the nitrite solution includes sodium nitrite and / or potassium nitrite.

[0044] Preferably, the mass fraction of nitrite in the nitrite solution is 30 - 40%. For example, it can be 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39% or 40%. However, it is not limited to the listed values, and other unlisted values within the above numerical range are equally applicable.

[0045] Preferably, the molar ratio of nitrite to o - fluoroaniline in the nitrite solution is (0.9 - 1.2):1. For example, it can be 0.9:1, 1.0:1, 1.1:1 or 1.2:1, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable.

[0046] As a preferred technical solution of the present invention, the temperature of the salt - forming reaction is - 10 to 20°C. For example, it can be - 10°C, - 5°C, 0°C, 5°C, 10°C, 15°C or 20°C, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable, and preferably it is - 5 to 10°C.

[0047] Preferably, the mass fraction of fluoboric acid in the fluoboric acid solution is 25 - 50%. For example, it can be 25%, 30%, 35%, 40%, 45% or 50%, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable.

[0048] Preferably, the molar ratio of fluoboric acid to o - fluoroaniline in the fluoboric acid solution is (0.8 - 1.3):1. For example, it can be 0.8:1, 0.9:1, 1.0:1, 1.1:1, 1.2:1 or 1.3:1, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable.

[0049] As a preferred technical solution of the present invention, the preparation method further includes separating the second reaction post - material containing fluoboric acid diazonium salt, and the fluoboric acid diazonium salt is obtained after separation.

[0050] Preferably, the separation treatment includes suction filtration treatment and drying treatment carried out in sequence.

[0051] Preferably, the temperature of the suction filtration treatment is - 15 to 5°C. For example, it can be - 15°C, - 10°C, - 5°C, 0°C or 5°C, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable, and preferably it is - 10 to 0°C.

[0052] Preferably, the temperature of the drying treatment is 40 to 65°C. For example, it can be 40°C, 45°C, 50°C, 55°C, 60°C or 65°C, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable, and preferably it is 50 to 55°C.

[0053] Preferably, the drying treatment includes any one or a combination of at least two of vacuum drying treatment, atmospheric pressure drying treatment, low-temperature drying treatment or microwave drying treatment. Typical but non-limiting combinations include: the combination of vacuum drying treatment and atmospheric pressure drying treatment, the combination of vacuum drying treatment and low-temperature drying treatment, the combination of vacuum drying treatment and microwave drying treatment, the combination of atmospheric pressure drying treatment and low-temperature drying treatment, the combination of atmospheric pressure drying treatment and microwave drying treatment, the combination of low-temperature drying treatment and microwave drying treatment, the combination of vacuum drying treatment, atmospheric pressure drying treatment and low-temperature drying treatment, the combination of vacuum drying treatment, atmospheric pressure drying treatment and microwave drying treatment, the combination of vacuum drying treatment, low-temperature drying treatment and microwave drying treatment, the combination of atmospheric pressure drying treatment, low-temperature drying treatment and microwave drying treatment, the combination of vacuum drying treatment, atmospheric pressure drying treatment, low-temperature drying treatment and microwave drying treatment.

[0054] Preferably, the degree of vacuum of the vacuum drying treatment is 2000 - 10000 Pa. For example, it can be 2000 Pa, 3000 Pa, 4000 Pa, 5000 Pa, 6000 Pa, 7000 Pa, 8000 Pa, 9000 Pa or 10000 Pa, but it is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable.

[0055] As a preferred technical solution of the present invention, the preparation method includes the following steps:

[0056] (1) Mix hydrochloric acid solution and o-fluoroaniline according to the molar ratio of hydrochloric acid to o-fluoroaniline in the hydrochloric acid solution being (1.0 - 2.4):1, heat to complete dissolution at 30 - 80 °C, and then cool to -15 - 5 °C to obtain an o-fluoroaniline hydrochloride solution;

[0057] (2) After mixing the o-fluoroaniline hydrochloride solution and the nitrite solution, introduce them into the reaction material layer of the first microchannel reactor for diazotization reaction for 5 - 10 s, where the temperature of the diazotization reaction is -5 - 35 °C. In order to maintain the temperature of the diazotization reaction, introduce a first heat exchange medium with a flow rate of 10 - 30 mL / min and a temperature of -20 - 0 °C into the first heat exchange medium layer and the second heat exchange medium layer of the first microchannel reactor independently to obtain a first post-reaction material;

[0058] (3) After mixing the fluoboric acid solution and the first post-reaction material, introduce them into the reaction material layer of the second microchannel reactor for salt formation reaction for 8 - 15 s, where the temperature of the salt formation reaction is -10 - 20 °C. In order to maintain the temperature of the salt formation reaction, introduce a second heat exchange medium with a flow rate of 20 - 50 mL / min and a temperature of -30 - -10 °C into the first heat exchange medium layer and the second heat exchange medium layer of the second microchannel reactor independently to obtain a second post-reaction material containing fluoboric acid diazonium salt;

[0059] (4) The second reaction product containing diazonium fluoroborate is successively subjected to suction filtration at a temperature of -15 to 5°C and drying at a temperature of 40 to 65°C to obtain the diazonium fluoroborate.

[0060] In a second aspect, the present invention provides a reaction apparatus for use in the preparation method described in the first aspect, the reaction apparatus including a reaction unit;

[0061] The reaction unit includes two microchannel reactors arranged in series;

[0062] The microchannel reactor has a sleeve structure, and the sleeve structure includes a first heat exchange medium layer, a reaction material layer, and a second heat exchange medium layer arranged in sequence from the inside out;

[0063] Turbulence components are independently provided inside the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer respectively.

[0064] The microchannel reactor of the present invention has a sleeve structure, and its inner, middle, and outer three-layer structures respectively correspond to the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer. Turbulence components are independently provided inside the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer. The turbulence components can avoid the channeling effect of the reaction materials; at the same time, the turbulence components in the reaction material layer can prevent the coalescence of droplets during the flow process, play a role in turbulent flow on the fluid, increase the liquid surface contact during its flow process, increase mass transfer and heat transfer, and improve the reaction efficiency.

[0065] As a preferred technical solution of the present invention, the reaction apparatus further includes a feeding unit, a mixing unit, and a separation unit.

[0066] Preferably, the feeding unit includes a liquid phase storage device independently connected to the reaction unit.

[0067] Preferably, the mixing unit is located between the feeding unit and the reaction unit.

[0068] Preferably, the mixing unit includes two mixers.

[0069] Preferably, the two mixers are arranged in parallel.

[0070] Preferably, the mixers are a first T-shaped mixer and a second T-shaped mixer.

[0071] Preferably, the first T-shaped mixer is connected to the inlet of the first microchannel reactor.

[0072] Preferably, the flow rate of o-fluoroaniline hydrochloride in the first T-shaped mixer is 1-15 mL / min, for example, it can be 1 mL / min, 3 mL / min, 5 mL / min, 8 mL / min, 10 mL / min, 12 mL / min or 15 mL / min, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable, and preferably it is 3-8 mL / min.

[0073] Preferably, the flow rate of the nitrite solution in the first T-shaped mixer is 0.5-10 mL / min, for example, it can be 0.5 mL / min, 1 mL / min, 3 mL / min, 5 mL / min, 8 mL / min or 10 mL / min, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable, and preferably it is 1-8 mL / min.

[0074] Preferably, the second T-shaped mixer is connected to the inlet of the second microchannel reactor.

[0075] Preferably, the flow rate of the fluoboric acid solution in the second T-shaped mixer is 1-15 mL / min, for example, it can be 1 mL / min, 3 mL / min, 5 mL / min, 8 mL / min, 10 mL / min, 12 mL / min or 15 mL / min, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable.

[0076] Preferably, the inner diameters of the first T-shaped mixer and the second T-shaped mixer are each independently 1000-2000 μm, for example, it can be 1000 μm, 1200 μm, 1400 μm, 1600 μm, 1800 μm or 2000 μm, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable.

[0077] Preferably, the feed ports of the two microchannel reactors each independently have a neck structure, and the cross-sectional area of the neck structure is smaller than the cross-sectional area of the reaction material layer.

[0078] In the present invention, by providing a neck structure at the feed port of the microchannel reactor, the degree of turbulence during the flow of the material can be increased. After passing through the neck structure, the material has a higher flow rate and a more violent disturbance phenomenon, which can further enhance mass transfer.

[0079] Preferably, the ratio of the cross-sectional area of the neck structure to the cross-sectional area of the reaction material layer is (0.7-0.9):1, for example, it can be 0.7:1, 0.75:1, 0.8:1, 0.85:1 or 0.9:1, but is not limited to the listed values. Other unlisted values within the above numerical range are equally applicable.

[0080] Preferably, the separation unit is connected to the reaction unit, and the reaction device is sequentially connected to the reaction unit and the separation unit along the material flow direction.

[0081] As a preferred technical solution of the present invention, the diameter of the reaction material layer is 300 - 800 μm, for example, it can be 300 μm, 400 μm, 500 μm, 600 μm, 700 μm or 800 μm, but is not limited to the listed values, and other unlisted values within the above value range are equally applicable.

[0082] Preferably, the diameter of the first heat exchange medium layer is 300 - 500 μm, for example, it can be 300 μm, 350 μm, 400 μm, 450 μm or 500 μm, but is not limited to the listed values, and other unlisted values within the above value range are equally applicable.

[0083] Preferably, the diameter of the second heat exchange medium layer is 200 - 400 μm, for example, it can be 200 μm, 250 μm, 300 μm, 350 μm or 400 μm, but is not limited to the listed values, and other unlisted values within the above value range are equally applicable.

[0084] Preferably, each of the first heat exchange medium layer, the reaction material layer and the second heat exchange medium layer independently includes at least five groups of the turbulence components, and two adjacent groups of the turbulence components are staggeredly distributed. For example, it can be five groups, seven groups, nine groups or ten groups, but is not limited to the listed values, and other unlisted values within the above value range are equally applicable.

[0085] Preferably, the material of the turbulence component includes any one or a combination of at least two of high molecular polymers, ceramics or metals. Typical but non - restrictive combinations include: a combination of high molecular polymers and ceramics, a combination of high molecular polymers and metals, a combination of ceramics and metals, and a combination of high molecular polymers, ceramics and metals.

[0086] Preferably, the shape of the turbulence component includes any one or a combination of at least two of a cylinder, a square or a rhombic column. Typical but non - restrictive combinations include: a combination of a cylinder and a square, a combination of a cylinder and a rhombic column, a combination of a square and a rhombic column, and a combination of a cylinder, a square and a rhombic column.

[0087] Preferably, the height of the turbulence component is 100 - 400 μm, for example, it can be 100 μm, 200 μm, 300 μm or 400 μm, but is not limited to the listed values, and other unlisted values within the above value range are equally applicable.

[0088] Preferably, the height-to-diameter ratio of the cylindrical flow disturbing component is (0.2 to 0.8):1. For example, it can be 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, 0.7:1 or 0.8:1. However, it is not limited to the listed values, and other unlisted values within the above numerical range are equally applicable.

[0089] The present invention uses a cylindrical flow disturbing component and defines the height-to-diameter ratio of the flow disturbing component as (0.2 to 0.8):1, which can increase the degree of turbulence during material flow and effectively avoid the occurrence of pipe blockage.

[0090] Compared with the prior art, the present invention has at least the following beneficial effects:

[0091] (1) The present invention uses a microchannel reactor to prepare diazonium fluoroborate. Compared with the traditional batch reactor, the microchannel reactor has a smaller liquid holdup, and its larger specific surface area also greatly improves the mass transfer and heat transfer capabilities of the reactor, can quickly remove heat, inhibit side reactions, and has stronger safety.

[0092] (2) The present invention uses a microchannel reactor for diazotization reaction and salt formation reaction, can control the temperature of the diazotization reaction within the range of -5 to 35°C, can reduce the use of solvents during the reaction, can shorten the reaction time to 50 to 100 s, improve the conversion rate of the reaction, and make the yield of diazonium fluoroborate reach more than 80%. Description of the Drawings

[0093] Figure 1 is the reaction device diagram for preparing diazonium fluoroborate in Example 1 of the present invention.

[0094] Figure 2 is the structural schematic diagram of the microchannel reactor used in Example 1 of the present invention.

[0095] Figure 3 is the reaction equation for preparing diazonium fluoroborate in Example 1 of the present invention.

[0096] Among them, 1 - the first liquid-phase storage tank; 2 - the second liquid-phase storage tank; 3 - the first T-shaped mixer; 4 - the first microchannel reactor; 5 - the third liquid-phase storage tank; 6 - the second T-shaped mixer; 7 - the second microchannel reactor; 8 - the suction filtration unit; 9 - the drying unit. Detailed Embodiments

[0097] The technical solutions of the present invention will be further described below with reference to the drawings and through specific embodiments. However, the following examples are only simple examples of the present invention and do not represent or limit the scope of the protection of the present invention. The scope of protection of the present invention is subject to the claims.

[0098] Example 1

[0099] This embodiment provides a method for preparing diazonium fluoroborate, and the reaction device used is as Figure 1 shown. The preparation method includes the following steps:

[0100] (1) In the first liquid-phase storage tank 1, a hydrochloric acid solution and o-fluoroaniline are mixed according to a molar ratio of hydrochloric acid to o-fluoroaniline in the hydrochloric acid solution of 1.8:1, heated to complete dissolution at 45 °C, and then cooled to -10 °C to obtain an o-fluoroaniline hydrochloride solution, wherein the mass fraction of hydrochloric acid in the hydrochloric acid solution is 30%;

[0101] (2) The o-fluoroaniline hydrochloride solution in the first liquid-phase storage tank 1 and the sodium nitrite solution with a mass fraction of 40% in the second liquid-phase storage tank 2 are introduced into the first T-shaped mixer 3 at a temperature of 0 °C, and the addition amount of sodium nitrite in the sodium nitrite solution is in a molar ratio of 1.1:1 to the o-fluoroaniline in step (1). The flow rate of the o-fluoroaniline hydrochloride solution in the first T-shaped mixer 3 is 8.22 mL / min, and the flow rate of the sodium nitrite solution in the first T-shaped mixer 3 is 2.9 mL / min. The uniformly mixed material is introduced into the reaction material layer of the first microchannel reactor 4 for a diazotization reaction for 8 s. To maintain the temperature of the diazotization reaction, propylene glycol with a flow rate of 15 mL / min and a temperature of -15 °C is introduced into the first heat exchange medium layer of the first microchannel reactor 4, and ethylene glycol with a flow rate of 15 mL / min and a temperature of -15 °C is introduced into the second heat exchange medium layer of the first microchannel reactor 4. During this diazotization reaction process, the temperature inside the reaction material layer is controlled at 10 °C to obtain a first post-reaction material, wherein propylene glycol and ethylene glycol are turbulently flowing in the first heat exchange medium layer and the second heat exchange medium layer respectively;

[0102] (3) The fluoroboric acid solution with a mass fraction of 40% of fluoroboric acid in the third liquid-phase storage tank 5 and the first post-reaction material are introduced into the second T-shaped mixer 6 at a temperature of -10 °C, and the addition amount of fluoroboric acid in the fluoroboric acid solution is in a molar ratio of 1.1:1 to the o-fluoroaniline in step (1). The flow rate of the fluoroboric acid solution in the second T-shaped mixer 6 is 4.3 mL / min. The uniformly mixed material is introduced into the reaction material layer of the second microchannel reactor 7 for a salt-forming reaction for 10 s. To maintain the temperature of the salt-forming reaction, ethylene glycol with a flow rate of 25 mL / min and a temperature of -20 °C is introduced into the first heat exchange medium layer of the second microchannel reactor 7, and propylene glycol with a flow rate of 25 mL / min and a temperature of -20 °C is introduced into the second heat exchange medium layer of the second microchannel reactor 7. During this salt-forming reaction process, the temperature inside the reaction material layer is controlled at -10 °C to obtain a second post-reaction material containing diazonium fluoroborate, wherein ethylene glycol and propylene glycol are turbulently flowing in the first heat exchange medium layer and the second heat exchange medium layer respectively;

[0103] (4) In the suction filtration unit 8, the second reaction product containing diazonium fluoroborate is successively subjected to suction filtration at a temperature of -10°C to obtain a filter cake, which is washed once with ethanol and once with petroleum ether respectively, and then vacuum dried in the drying unit 9 at a temperature of 55°C and a vacuum degree of 3000 Pa to obtain the diazonium fluoroborate. The reaction equation in the preparation process of diazonium fluoroborate is as Figure 3 shown.

[0104] Specifically, the inner diameter of the first T-shaped mixer 3 is 1500 μm, and the inner diameter of the second T-shaped mixer 6 is 1800 μm;

[0105] The first microchannel reactor 4 has a double-tube structure, as Figure 2 shown. From the inside out, it includes a first heat exchange medium layer with five groups of turbulator components made of high-alumina porcelain, square in shape, and 150 μm in height arranged inside, a reaction material layer with seven groups of turbulator components made of copper, cylindrical in shape, 300 μm in height, and a height-to-diameter ratio of 0.6:1 arranged inside, and a second heat exchange medium layer with nine groups of turbulator components made of nylon 6 (PA6), cylindrical in shape, 100 μm in height, and a height-to-diameter ratio of 0.6:1 arranged inside. Among them, two adjacent groups of the turbulator components are staggered. The diameters of the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer are 300 μm, 500 μm, and 200 μm respectively. At the same time, the feed inlet of the first microchannel reactor 4 has a neck structure, where the diameter of the neck structure of the first heat exchange medium layer is 450 μm, that is, the cross-sectional area ratio of the neck structure to the cross-sectional area of the reaction material layer is 0.81:1;

[0106] The second microchannel reactor 7 has a double-tube structure. From the inside out, it includes a first heat exchange medium layer with seven groups of turbulator components made of magnesia porcelain, cylindrical in shape, 150 μm in height, and a height-to-diameter ratio of 0.6:1 arranged inside, a reaction material layer with five groups of turbulator components made of iron, cylindrical in shape, 350 μm in height, and a height-to-diameter ratio of 0.6:1 arranged inside, and a second heat exchange medium layer with five groups of turbulator components made of polytetrafluoroethylene (PTFE-BP), cylindrical in shape, 200 μm in height, and a height-to-diameter ratio of 0.6:1 arranged inside. Among them, two adjacent groups of the turbulator components are staggered. The diameters of the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer are 300 μm, 600 μm, and 400 μm respectively. At the same time, the feed inlet of the second microchannel reactor 7 has a neck structure, where the diameter of the neck structure of the first heat exchange medium layer is 500 μm, that is, the cross-sectional area ratio of the neck structure to the cross-sectional area of the reaction material layer is 0.7:1.

[0107] Example 2

[0108] This embodiment provides a method for preparing diazonium fluoroborate. The preparation method includes the following steps:

[0109] (1) In the first liquid-phase storage tank, a hydrochloric acid solution and o-fluoroaniline are mixed according to a molar ratio of hydrochloric acid to o-fluoroaniline in the hydrochloric acid solution of 1:1, heated to complete dissolution at 80 °C, and then cooled to -15 °C to obtain an o-fluoroaniline hydrochloride solution. Among them, the mass fraction of hydrochloric acid in the hydrochloric acid solution is 38%;

[0110] (2) The o-fluoroaniline hydrochloride solution in the first liquid-phase storage tank and the potassium nitrite solution with a mass fraction of 35% in the second liquid-phase storage tank are introduced into a first T-shaped mixer at a temperature of -10 °C, and the addition amount of potassium nitrite in the potassium nitrite solution is in a molar ratio of 1.2:1 to the o-fluoroaniline in step (1). The flow rate of the o-fluoroaniline hydrochloride solution in the first T-shaped mixer is 6.77 mL / min, and the flow rate of the potassium nitrite solution in the first T-shaped mixer is 3.75 mL / min. The uniformly mixed material is introduced into the reaction material layer of the first microchannel reactor for a diazotization reaction for 5 s. In order to maintain the temperature of the diazotization reaction, ethylene glycol with a flow rate of 10 mL / min and a temperature of -20 °C is introduced into the first heat exchange medium layer of the first microchannel reactor, and a brine solution with a flow rate of 30 mL / min and a temperature of 0 °C is introduced into the second heat exchange medium layer of the first microchannel reactor. During this diazotization reaction, the temperature inside the reaction material layer is controlled at -5 °C to obtain a first post-reaction material, where ethylene glycol and the brine solution are in turbulent flow in the first heat exchange medium layer and the second heat exchange medium layer respectively;

[0111] (3) The fluoroboric acid solution with a mass fraction of 50% of fluoroboric acid in the third liquid-phase storage tank and the first post-reaction material are introduced into a second T-shaped mixer at a temperature of -15 °C, and the addition amount of fluoroboric acid in the fluoroboric acid solution is in a molar ratio of 0.8:1 to the o-fluoroaniline in step (1). The flow rate of the fluoroboric acid solution in the second T-shaped mixer is 3.06 mL / min. The uniformly mixed material is introduced into the reaction material layer of the second microchannel reactor for a salt-forming reaction for 8 s. In order to maintain the temperature of the salt-forming reaction, propylene glycol with a flow rate of 20 mL / min and a temperature of -10 °C is introduced into the first heat exchange medium layer of the second microchannel reactor, and a brine solution with a flow rate of 20 mL / min and a temperature of -10 °C is introduced into the second heat exchange medium layer of the second microchannel reactor. During this salt-forming reaction, the temperature inside the reaction material layer is controlled at 0 °C to obtain a second post-reaction material containing diazonium fluoroborate, where propylene glycol and the brine solution are in turbulent flow in the first heat exchange medium layer and the second heat exchange medium layer respectively;

[0112] (4) In the suction filtration unit, the second reaction product containing diazonium fluoroborate is successively subjected to suction filtration at a temperature of 5°C to obtain a filter cake, which is washed twice with ethanol and petroleum ether respectively, and then subjected to atmospheric drying at a temperature of 40°C in the drying unit to obtain the diazonium fluoroborate.

[0113] Specifically, the inner diameter of the first T-shaped mixer is 1000 μm, and the inner diameter of the second T-shaped mixer is 2000 μm;

[0114] The first microchannel reactor has a double-tube structure and includes, from the inside out, a first heat exchange medium layer with nine sets of turbulator components made of polytetrafluoroethylene (PTFE-BP), cylindrical in shape, 100 μm in height, and with a height-to-diameter ratio of 0.8:1, a reaction material layer with seven sets of turbulator components made of aluminum, cylindrical in shape, 250 μm in height, and with a height-to-diameter ratio of 0.8:1, and a second heat exchange medium layer with nine sets of turbulator components made of titan-magnesia porcelain, rhombic column in shape, 400 μm in height. Among them, two adjacent sets of the turbulator components are staggeredly distributed. The diameters of the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer are 300 μm, 300 μm, and 200 μm respectively. At the same time, the feed inlet of the first microchannel reactor has a neck structure, where the diameter of the neck structure of the first heat exchange medium layer is 285 μm, that is, the cross-sectional area ratio of the neck structure to the cross-sectional area of the reaction material layer is 0.9:1;

[0115] The second microchannel reactor has a double-tube structure and includes, from the inside out, a first heat exchange medium layer with seven sets of turbulator components made of aluminum, square in shape, 120 μm in height, a reaction material layer with five sets of turbulator components made of nylon 6 (PA6), cylindrical in shape, 300 μm in height, and with a height-to-diameter ratio of 0.8:1, and a second heat exchange medium layer with seven sets of turbulator components made of magnesia porcelain, cylindrical in shape, 100 μm in height, and with a height-to-diameter ratio of 0.8:1. Among them, two adjacent sets of the turbulator components are staggeredly distributed. The diameters of the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer are 500 μm, 800 μm, and 400 μm respectively. At the same time, the feed inlet of the second microchannel reactor has a neck structure, where the diameter of the neck structure of the first heat exchange medium layer is 670 μm, that is, the cross-sectional area ratio of the neck structure to the cross-sectional area of the reaction material layer is 0.7:1.

[0116] Example 3

[0117] This example provides a method for preparing diazonium fluoroborate, and the preparation method includes the following steps:

[0118] (1) Mix hydrochloric acid solution and o - fluoroaniline in the first liquid - phase storage tank according to the molar ratio of hydrochloric acid to o - fluoroaniline in the hydrochloric acid solution being 2:1, heat it to complete dissolution at 30°C, and then cool it to 5°C to obtain o - fluoroaniline hydrochloride solution. Among them, the mass fraction of hydrochloric acid in the hydrochloric acid solution is 34%;

[0119] (2) Feed the o - fluoroaniline hydrochloride solution in the first liquid - phase storage tank and the sodium nitrite solution with a mass fraction of 30% in the second liquid - phase storage tank into the first T - type mixer at a temperature of 20°C, and make the addition amount of sodium nitrite in the sodium nitrite solution and the molar ratio of o - fluoroaniline in step (1) be 0.9:1. The flow rate of the o - fluoroaniline hydrochloride solution in the first T - type mixer is 8.27 mL / min, and the flow rate of the sodium nitrite solution in the first T - type mixer is 2.38 mL / min. Feed the uniformly mixed material into the reaction material layer of the first micro - channel reactor for a diazotization reaction for 10 s. In order to maintain the temperature of the diazotization reaction, feed propylene glycol with a flow rate of 30 mL / min and a temperature of 0°C into the first heat - exchange medium layer of the first micro - channel reactor, and feed ethylene glycol with a flow rate of 10 mL / min and a temperature of - 20°C into the second heat - exchange medium layer of the first micro - channel reactor. Control the temperature inside the reaction material layer during this diazotization reaction to be 35°C to obtain the first post - reaction material, where propylene glycol and ethylene glycol flow turbulently in the first heat - exchange medium layer and the second heat - exchange medium layer respectively;

[0120] (3) Feed the fluoroboric acid solution with a mass fraction of 25% of fluoroboric acid in the third liquid - phase storage tank and the first post - reaction material into the second T - type mixer at a temperature of 5°C, and make the addition amount of fluoroboric acid in the fluoroboric acid solution and the molar ratio of o - fluoroaniline in step (1) be 1.3:1. The flow rate of the fluoroboric acid solution in the second T - type mixer is 5.40 mL / min. Feed the uniformly mixed material into the reaction material layer of the second micro - channel reactor for a salt - forming reaction for 15 s. In order to maintain the temperature of the salt - forming reaction, feed ethylene glycol with a flow rate of 50 mL / min and a temperature of - 30°C into the first heat - exchange medium layer of the second micro - channel reactor, and feed propylene glycol with a flow rate of 50 mL / min and a temperature of - 30°C into the second heat - exchange medium layer of the second micro - channel reactor. Control the temperature inside the reaction material layer during this salt - forming reaction to be 20°C to obtain the second post - reaction material containing fluoroboric acid diazonium salt, where ethylene glycol and propylene glycol flow turbulently in the first heat - exchange medium layer and the second heat - exchange medium layer respectively;

[0121] (4) Conduct suction filtration treatment at a temperature of - 15°C on the second post - reaction material containing fluoroboric acid diazonium salt in the suction filtration unit to obtain a filter cake, wash the filter cake once with ethanol and once with petroleum ether respectively, and then conduct microwave drying treatment at a temperature of 65°C in the drying unit to obtain the fluoroboric acid diazonium salt.

[0122] Specifically, the inner diameter of the first T-shaped mixer is 2000 μm, and the inner diameter of the second T-shaped mixer is 1000 μm;

[0123] The first microchannel reactor has a casing structure and includes, from the inside out, a first heat exchange medium layer with seven sets of turbulator components made of aluminum, cylindrical in shape, 200 μm in height, and with a height-to-diameter ratio of 0.5:1, a reaction material layer with five sets of turbulator components made of polytetrafluoroethylene (PTFE-BP), cylindrical in shape, 200 μm in height, and with a height-to-diameter ratio of 0.5:1, and a second heat exchange medium layer with seven sets of turbulator components made of high-alumina porcelain, cylindrical in shape, 100 μm in height, and with a height-to-diameter ratio of 0.2:1. Among them, two adjacent sets of the turbulator components are staggeredly distributed. The diameters of the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer are 300 μm, 700 μm, and 200 μm respectively. At the same time, the inlet of the first microchannel reactor has a neck structure. Among them, the diameter of the neck structure of the first heat exchange medium layer is 630 μm, that is, the cross-sectional area ratio of the neck structure to the cross-sectional area of the reaction material layer is 0.81:1;

[0124] The second microchannel reactor has a casing structure and includes, from the inside out, a first heat exchange medium layer with nine sets of turbulator components made of nylon 6 (PA6), cylindrical in shape, 100 μm in height, and with a height-to-diameter ratio of 0.2:1, a reaction material layer with seven sets of turbulator components made of aluminum, cylindrical in shape, 150 μm in height, and with a height-to-diameter ratio of 0.5:1, and a second heat exchange medium layer with nine sets of turbulator components made of titanium-magnesium stone porcelain, cylindrical in shape, 200 μm in height, and with a height-to-diameter ratio of 0.5:1. Among them, two adjacent sets of the turbulator components are staggeredly distributed. The diameters of the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer are 300 μm, 400 μm, and 200 μm respectively. At the same time, the inlet of the second microchannel reactor has a neck structure. Among them, the diameter of the neck structure of the first heat exchange medium layer is 360 μm, that is, the cross-sectional area ratio of the neck structure to the cross-sectional area of the reaction material layer is 0.81:1.

[0125] Example 4

[0126] This example provides a method for preparing diazonium fluoroborate. The difference from Example 1 is only that except that the first heat exchange medium layer is not contained in the first microchannel reactor, the rest are the same as in Example 1.

[0127] Example 5

[0128] This embodiment provides a method for preparing diazonium fluoroborate, which is only different from Embodiment 1 in that, except that the first microchannel reactor does not contain the second heat exchange medium layer, the rest are the same as Embodiment 1.

[0129] Embodiment 6

[0130] This embodiment provides a method for preparing diazonium fluoroborate, which is only different from Embodiment 1 in that, except that the second microchannel reactor does not contain the first heat exchange medium layer, the rest are the same as Embodiment 1.

[0131] Embodiment 7

[0132] This embodiment provides a method for preparing diazonium fluoroborate, which is only different from Embodiment 1 in that, except that the second microchannel reactor does not contain the second heat exchange medium layer, the rest are the same as Embodiment 1.

[0133] Embodiment 8

[0134] This embodiment provides a method for preparing diazonium fluoroborate, which is only different from Embodiment 1 in that, except that the first heat exchange medium layer in the first microchannel reactor does not contain a turbulence component, that is, propylene glycol flows in a plug flow in the first heat exchange medium layer, the rest are the same as Embodiment 1.

[0135] Embodiment 9

[0136] This embodiment provides a method for preparing diazonium fluoroborate, which is only different from Embodiment 1 in that, except that the second heat exchange medium layer in the first microchannel reactor does not contain a turbulence component, that is, ethylene glycol flows in a plug flow in the first heat exchange medium layer, the rest are the same as Embodiment 1.

[0137] Embodiment 10

[0138] This embodiment provides a method for preparing diazonium fluoroborate, which is only different from Embodiment 1 in that, except that the feed port of the first microchannel reactor is not provided with a neck structure, the rest are the same as Embodiment 1.

[0139] Embodiment 11

[0140] This embodiment provides a method for preparing diazonium fluoroborate, which is only different from Embodiment 1 in that, except that the aspect ratio of the cylindrical turbulence component in the reaction material layer of the first microchannel reactor is 0.1:1, the rest are the same as Embodiment 1.

[0141] Embodiment 12

[0142] This embodiment provides a method for preparing diazonium fluoroborate, which is only different from Embodiment 1 in that, except that the aspect ratio of the cylindrical turbulence component in the reaction material layer of the first microchannel reactor is 1:1, the rest are the same as Embodiment 1.

[0143] Comparative Example 1

[0144] This comparative example provides a method for preparing diazonium fluoroborate. The difference from Example 1 is only that, except for carrying out the diazotization reaction in a 500 mL three-necked polytetrafluoroethylene flask (PTFE-500 mL), that is, dropping a 40% sodium nitrite solution into the o-fluoroaniline hydrochloride solution at a dropping rate of 0.138 mL / min for a dropping time of 2 h, and after the dropping is completed, maintaining the temperature at 0-20 °C and stirring for 30 min, the rest are the same as in Example 1.

[0145] Comparative Example 2

[0146] This comparative example provides a method for preparing diazonium fluoroborate. The difference from Example 1 is only that, except for carrying out the salt-forming reaction in a 500 mL three-necked polytetrafluoroethylene flask (PTFE-500 mL), that is, dropping a 40% fluoboric acid solution into the first reaction product at a dropping rate of 0.276 mL / min for a dropping time of 1 h, and after the dropping is completed, maintaining the temperature at -20 to -5 °C and stirring for 1 h, the rest are the same as in Example 1.

[0147] Comparative Example 3

[0148] This comparative example provides a method for preparing diazonium fluoroborate. The difference from Example 1 is only that, except for first carrying out the salt-forming reaction between the o-fluoroaniline hydrochloride solution and the fluoboric acid solution and then carrying out the diazotization reaction with sodium nitrite, that is, first carrying out the salt-forming reaction in step (3) between the o-fluoroaniline hydrochloride solution and the fluoboric acid solution, and then carrying out the diazotization reaction in step (2) between the resulting product and the sodium nitrite solution, the rest are the same as in Example 1.

[0149] Use an electronic balance to weigh the mass of the prepared diazonium fluoroborate, and calculate the yield of the diazonium fluoroborate according to the following formula:

[0150] where m 理论 = n×209.92, n is the number of moles of o-fluoroaniline added during the reaction, and the molecular weight of diazonium fluoroborate is 209.92.

[0151] Meanwhile, the prepared diazonium fluoroborate contains impurities such as unreacted o-fluoroaniline, oxidation by-products, phenols or other derivatives, chlorides, etc. The contents of o-fluoroaniline and azo by-product impurities are tested by liquid chromatography, and the sum of the contents of o-fluoroaniline and azo by-product impurities is obtained as the content of key impurities. The test results are shown in Table 1.

[0152] Table 1

[0153]

[0154]

[0155] It can be seen from the test results that:

[0156] (1) It can be seen from Examples 1 to 3 that by using a microchannel reactor to prepare diazonium fluoroborate, the temperature of the diazotization reaction can be controlled within the range of -5 to 35 °C in the present invention, so as to improve the reaction stability, making the conversion rate of raw materials reach more than 88.4%, the total content of key impurities controlled below 7.2%, and the yield of diazonium fluoroborate reach more than 90.3%.

[0157] (2) It can be seen from Example 1 and Examples 4 - 5 that the first microchannel reactor used in Example 1 includes a first heat exchange medium layer, a reaction material layer, and a second heat exchange medium layer arranged in sequence from the inside out. When using this first microchannel reactor for diazotization reaction, the temperature of the diazotization reaction can be controlled within 8 to 12 °C, the conversion rate of its raw materials is 91.8%, and the yield of diazonium fluoroborate is 93.9%; while the first microchannel reactor used in Example 4 only includes a reaction material layer and a second heat exchange medium layer arranged in sequence from the inside out. When using this first microchannel reactor for diazotization reaction, the temperature of the diazotization reaction can be controlled within 5 to 20 °C, the conversion rate of its raw materials is 83.4%, and the yield of diazonium fluoroborate is 87.7%. The microchannel reactor used in Example 5 includes a first heat exchange medium layer and a reaction material layer arranged in sequence from the inside out. When using this first microchannel reactor for diazotization reaction, the temperature of the diazotization reaction can be controlled within 10 to 25 °C, the conversion rate of its raw materials is 79.6%, and the yield of diazonium fluoroborate is 84.8%. Thus, it shows that in the present invention, when using a microchannel reactor with a three-layer sleeve structure for diazotization reaction, the reaction material is introduced into the middle layer of the microchannel, and heat exchange medium layers are respectively arranged on the inner side and the outer side of the reaction material. The heat exchange medium is used to perform convective heat transfer on the reaction material on the inner side and the outer side of the reaction material respectively, which can increase the heat transfer effect to control the reaction temperature and improve the reaction stability.

[0158] (3) It can be seen from Example 1 and Examples 6 - 7 that the second microchannel reactor used in Example 1 includes a first heat exchange medium layer, a reaction material layer, and a second heat exchange medium layer arranged in sequence from the inside out. When using this second microchannel reactor for the salt - forming reaction, the conversion rate of the raw material can reach 91.8%, and the yield of diazonium fluoroborate is 93.9%. While the second microchannel reactor used in Example 6 includes a reaction material layer and a second heat exchange medium layer arranged in sequence from the inside out. When using this second microchannel reactor for the salt - forming reaction, the conversion rate of the raw material is 87.1%, and the yield of diazonium fluoroborate is 89.3%. The second microchannel reactor used in Example 7 includes a first heat exchange medium layer and a reaction material layer arranged in sequence from the inside out. When using this second microchannel reactor for the salt - forming reaction, the conversion rate of the raw material is 82.6%, and the yield of diazonium fluoroborate is 86.7%. Thus, it is shown that when using the microchannel reactor with a three - layer sleeve structure for the salt - forming reaction in the present invention, the reaction material is introduced into the middle layer of the microchannel, and heat exchange medium layers are respectively arranged on the inner side and the outer side of the reaction material. The heat exchange medium is used to perform convective heat transfer on the reaction material on the inner side and the outer side of the reaction material respectively, which can increase the heat transfer effect to control the reaction temperature and improve the reaction stability.

[0159] (4) It can be seen from Example 1 and Examples 8-9 that inside the first heat exchange medium layer of the first microchannel reactor used in Example 1, there are five groups of flow disturbance components made of high-alumina porcelain, with a square shape and a height of 150 μm. Inside the second heat exchange medium layer, there are nine groups of flow disturbance components made of nylon 6 (PA6), with a cylindrical shape, a height of 100 μm, and a height-to-diameter ratio of 0.6:1. That is, propylene glycol and ethylene glycol respectively undergo turbulent flow in the first and second heat exchange medium layers. When using this first microchannel reactor for the diazotization reaction, the temperature of the diazotization reaction can be controlled within 8-12°C, the conversion rate of the raw materials is 91.8%, the total content of key impurities is 2.1%, and the yield of diazonium fluoroborate is 93.9%. In Example 8, the first heat exchange medium layer inside the first microchannel reactor does not contain flow disturbance components, that is, propylene glycol undergoes plug flow in the first heat exchange medium layer. When using this first microchannel reactor for the diazotization reaction, the temperature of the diazotization reaction can be controlled within 15-25°C, the conversion rate of the raw materials is 74.9%, the total content of key impurities is 7.6%, and the yield of diazonium fluoroborate is 78.6%. In Example 9, the second heat exchange medium layer inside the first microchannel reactor does not contain flow disturbance components, that is, ethylene glycol undergoes plug flow in the second heat exchange medium layer. When using this first microchannel reactor for the diazotization reaction, the temperature of the diazotization reaction can be controlled within 18-25°C, the conversion rate of the raw materials is 69.1%, the total content of key impurities is 5.2%, and the yield of diazonium fluoroborate is 74.3%. This shows that the reaction heat involved in the diazotization reaction and salt formation reaction in the present invention is very large, and the temperature control requirement for the entire reaction process is relatively high. When the reaction heat cannot be transferred in time, the occurrence of side reactions will increase, and high-purity diazonium fluoroborate cannot be prepared. By defining the flow state of the heat exchange medium in the first microchannel reactor as turbulent flow, the present invention can break the thermal boundary layer, reduce the thermal resistance, significantly improve the heat transfer efficiency, and at the same time make the temperature distribution of the heat exchange medium more uniform, avoiding local overheating or overcooling from affecting the heat exchange effect on the reaction materials. Further, turbulent flow can increase the heat exchange efficiency for the reaction materials by reducing the flow dead zone and avoiding local retention.

[0160] (5) It can be seen from Example 1 and Example 10 that at the feed inlet of the first microchannel reactor used in Example 1, a neck structure is provided, and the ratio of the cross-sectional area of the neck structure to the cross-sectional area of the reaction material layer is defined as 0.81:1. When using this first microchannel reactor for the diazotization reaction, the temperature of the diazotization reaction can be controlled within 8 - 12 °C, the conversion rate of the raw materials is 91.8%, and the yield of diazonium fluoroborate is 93.9%. While in Example 10, no neck structure is provided at the feed inlet of the first microchannel reactor. When using this first microchannel reactor for the diazotization reaction, the temperature of the diazotization reaction can be controlled within 7 - 20 °C, the conversion rate of the raw materials is 85.7%, and the yield of diazonium fluoroborate is 89.3%. This shows that by providing a neck structure at the feed inlet of the microchannel reactor in the present invention, the turbulence degree during the material flow can be increased. After passing through the neck structure, the material has a higher flow rate and more intense disturbance phenomenon, which can further enhance mass transfer to increase the yield of diazonium fluoroborate.

[0161] (6) It can be seen from Example 1 and Examples 11 - 12 that for the first microchannel reactor used in Example 1, the ratio of the height to the diameter of the cylindrical flow disturbance component in the reaction material layer is 0.6:1. When using this first microchannel reactor for the diazotization reaction, the temperature of the diazotization reaction can be controlled within 8 - 12 °C, the conversion rate of the raw materials is 91.8%, and the yield of diazonium fluoroborate is 93.9%. While in Example 11, the ratio of the height to the diameter of the cylindrical flow disturbance component in the reaction material layer of the first microchannel reactor is 0.1:1. When using this first microchannel reactor for the diazotization reaction, the temperature of the diazotization reaction can be controlled within 5 - 15 °C, the conversion rate of the raw materials is 88.5%, and the yield of diazonium fluoroborate is 91.1%. In Example 12, the ratio of the height to the diameter of the cylindrical flow disturbance component in the reaction material layer of the first microchannel reactor is 1:1. When using this first microchannel reactor for the diazotization reaction, the temperature of the diazotization reaction can be controlled within 7 - 20 °C, the conversion rate of the raw materials is 85.1%, and the yield of diazonium fluoroborate is 88.2%. This shows that by using a cylindrical flow disturbance component in the present invention and defining the ratio of the height to the diameter of the flow disturbance component as (0.2 - 0.8):1, the turbulence degree during the material flow can be increased, effectively avoiding the occurrence of pipe blockage to increase the yield of diazonium fluoroborate.

[0162] (7) It can be seen from Example 1 and Comparative Examples 1 - 2 that by using a microchannel reactor for the diazotization reaction and the salt formation reaction in the present invention, the temperature of the diazotization reaction can be controlled within 8 - 12 °C, and a continuous production of a target product with relatively high purity can be obtained.

[0163] (8) It can be seen from Example 1 and Comparative Example 3 that, compared with the process of first carrying out a salt-forming reaction between o-fluoroaniline hydrochloride solution and fluoboric acid and then carrying out a diazotization reaction with nitrite, in the present invention, the o-fluoroaniline hydrochloride solution and nitrite are first used for the diazotization reaction and then the salt-forming reaction is carried out with fluoboric acid, which can improve the stability of the diazonium salt, avoid decomposition, and can improve the purity of the product. The intermediate generated during the diazotization of aromatic amines is very active and may lead to side reactions. That is, carrying out the diazotization reaction first and then the salt-forming reaction can convert the diazonium salt into the final product faster, thereby effectively controlling the generation of by-products, and this process can increase the conversion rate of the reaction.

[0164] In summary, the present invention prepares fluoboric acid diazonium salt by using a microchannel reactor. The microchannel reactor has a smaller liquid holdup, and its larger specific surface area also greatly improves the mass transfer and heat transfer capabilities of the reactor, can quickly remove heat, inhibit side reactions, and can precisely control the temperatures of the diazotization reaction and the salt-forming reaction to improve the stability of the reaction and obtain a product with high purity.

[0165] The applicant declares that the above description is only the specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by any person skilled in the art within the technical scope disclosed by the present invention fall within the protection scope and the disclosure scope of the present invention.

Claims

1. A method for preparing a diazonium fluoroborate, characterized in that, The preparation method comprises the following steps: (1) Feeding a first reaction material into a first microchannel reactor for diazotization reaction to obtain a first post-reaction material, wherein the first reaction material comprises an o-fluoroaniline hydrochloride solution and a nitrite solution; (2) Feeding a fluoboric acid solution and the first post-reaction material into a second microchannel reactor for salt formation reaction to obtain a second post-reaction material containing fluoboric acid diazonium salt.

2. The preparation method according to claim 1, characterized in that, The first microchannel reactor and the second microchannel reactor each independently comprise, from the inside out, a first heat exchange medium layer, a reaction material layer, and a second heat exchange medium layer arranged in sequence; the first reaction material is fed into the reaction material layer of the first microchannel reactor, and a first heat exchange medium is independently fed into the first heat exchange medium layer and the second heat exchange medium layer of the first microchannel reactor; Preferably, the first heat exchange medium in the first heat exchange medium layer and the second heat exchange medium layer of the first microchannel reactor forms a turbulent flow; Preferably, the flow rate of the first heat exchange medium is 10 - 30 mL / min; Preferably, the temperature of the first heat exchange medium is -20 - 0 °C; Preferably, the residence time of the first reaction material in the first microchannel reactor is 5 - 10 s; Preferably, the fluoboric acid solution and the first post-reaction material are fed into the reaction material layer of the second microchannel reactor, and a second heat exchange medium is independently fed into the first heat exchange medium layer and the second heat exchange medium layer of the second microchannel reactor; Preferably, the second heat exchange medium in the first heat exchange medium layer and the second heat exchange medium layer of the second microchannel reactor forms a turbulent flow; Preferably, the flow rate of the second heat exchange medium is 20 - 50 mL / min; Preferably, the temperature of the second heat exchange medium is -30 - -10 °C; Preferably, the first heat exchange medium and the second heat exchange medium each independently comprise any one or a combination of at least two of ethylene glycol, propylene glycol, or a brine solution; Preferably, the residence time of the fluoboric acid solution and the first post-reaction material in the second microchannel reactor is 8 - 15 s.

3. The preparation method according to claim 1 or 2, characterized in that, The preparation method of the o-fluoroaniline hydrochloride comprises: mixing a hydrochloric acid solution and o-fluoroaniline, heating to complete dissolution, and then cooling to a predetermined temperature to obtain the o-fluoroaniline hydrochloride solution; Preferably, the heating temperature is 30 - 80 °C, preferably 40 - 50 °C; Preferably, the mass fraction of hydrochloric acid in the hydrochloric acid solution is 30 - 38%; Preferably, the molar ratio of hydrochloric acid to o-fluoroaniline in the hydrochloric acid solution is (1.0 - 2.4):1, preferably (1.4 - 2.0):1; Preferably, the predetermined temperature is -15 - 5 °C.

4. The preparation method according to any one of claims 1 to 3, characterized in that, The temperature of the first reaction material is -10 - 20 °C, preferably -5 - 5 °C; Preferably, the temperature of the diazotization reaction is -5 - 35 °C, preferably 0 - 20 °C; Preferably, the nitrite in the nitrite solution comprises sodium nitrite and / or potassium nitrite; Preferably, the mass fraction of nitrite in the nitrite solution is 30 - 40%; Preferably, the molar ratio of nitrite to o - fluoroaniline in the nitrite solution is (0.9 - 1.2):

1.

5. The preparation method according to any one of claims 1-4, characterized in that, The temperature of the salt - forming reaction is - 10 to 20°C, preferably - 5 to 10°C; Preferably, the mass fraction of fluoboric acid in the fluoboric acid solution is 25 - 50%; Preferably, the molar ratio of fluoboric acid to o - fluoroaniline in the fluoboric acid solution is (0.8 - 1.3):

1.

6. The preparation method according to any one of claims 1-5, characterized in that, The preparation method further includes separating the second reaction product containing fluoboric acid diazonium salt to obtain the fluoboric acid diazonium salt; Preferably, the separation treatment includes suction filtration treatment and drying treatment carried out in sequence; Preferably, the temperature of the suction filtration treatment is - 15 to 5°C, preferably - 10 to 0°C; Preferably, the temperature of the drying treatment is 40 to 65°C, preferably 50 to 55°C; Preferably, the drying treatment includes any one or a combination of at least two of vacuum drying treatment, atmospheric drying treatment, low - temperature drying treatment or microwave drying treatment; Preferably, the vacuum degree of the vacuum drying treatment is 2000 - 10000 Pa.

7. The preparation method according to any one of claims 1-6, characterized in that, The preparation method includes the following steps: (1) Mix a hydrochloric acid solution and o - fluoroaniline according to the molar ratio of hydrochloric acid to o - fluoroaniline in the hydrochloric acid solution being (1.0 - 2.4):1, heat to complete dissolution at 30 - 80°C, and then cool to - 15 to 5°C to obtain an o - fluoroaniline hydrochloride solution; (2) Mix the o - fluoroaniline hydrochloride solution and a nitrite solution, and introduce them into the reaction material layer of the first microchannel reactor for a diazotization reaction for 5 - 10 s. The temperature of the diazotization reaction is - 5 to 35°C. To maintain the temperature of the diazotization reaction, a first heat - exchange medium with a flow rate of 10 - 30 mL / min and a temperature of - 20 to 0°C is independently introduced into the first heat - exchange medium layer and the second heat - exchange medium layer of the first microchannel reactor to obtain a first reaction product; (3) Mix the fluoboric acid solution with the first reaction product, and introduce them into the reaction material layer of the second microchannel reactor for a salt - forming reaction for 8 - 15 s. The temperature of the salt - forming reaction is - 10 to 20°C. To maintain the temperature of the salt - forming reaction, a second heat - exchange medium with a flow rate of 20 - 50 mL / min and a temperature of - 30 to - 10°C is independently introduced into the first heat - exchange medium layer and the second heat - exchange medium layer of the second microchannel reactor to obtain a second reaction product containing fluoboric acid diazonium salt; (4) Carry out suction filtration treatment at a temperature of - 15 to 5°C and drying treatment at a temperature of 40 to 65°C on the second reaction product containing fluoboric acid diazonium salt in sequence to obtain the fluoboric acid diazonium salt.

8. A reaction device for use in the preparation method according to any one of claims 1-7, characterized in that, The reaction device includes a reaction unit; The reaction unit includes two microchannel reactors arranged in series; The microchannel reactor is of a double - tube structure, and the double - tube structure includes a first heat - exchange medium layer, a reaction material layer and a second heat - exchange medium layer arranged in sequence from the inside out; Turbulence components are independently arranged inside the first heat - exchange medium layer, the reaction material layer and the second heat - exchange medium layer.

9. The reaction device according to claim 8, wherein The reaction device further includes a feeding unit, a mixing unit, and a separation unit; Preferably, the feeding unit includes a liquid-phase storage device independently connected to the reaction unit; Preferably, the mixing unit is located between the feeding unit and the reaction unit; Preferably, the mixing unit includes two mixers; Preferably, the two mixers are arranged in parallel; Preferably, the mixers are a first T-shaped mixer and a second T-shaped mixer; Preferably, the first T-shaped mixer is connected to the inlet of the first microchannel reactor; Preferably, the second T-shaped mixer is connected to the inlet of the second microchannel reactor; Preferably, the inner diameters of the first T-shaped mixer and the second T-shaped mixer are independently 1000-2000 μm; Preferably, the feeding ports of the two microchannel reactors each independently have a neck structure, and the cross-sectional area of the neck structure is smaller than the cross-sectional area of the reaction material layer; Preferably, the ratio of the cross-sectional area of the neck structure to the cross-sectional area of the reaction material layer is (0.7-0.9):1; Preferably, the separation unit is connected to the reaction unit, and the reaction device is sequentially connected to the reaction unit and the separation unit along the material flow direction.

10. The reaction device according to claim 8 or 9, characterized in that, The diameter of the reaction material layer is 300-800 μm; Preferably, the diameter of the first heat exchange medium layer is 300-500 μm; Preferably, the diameter of the second heat exchange medium layer is 200-400 μm; Preferably, the first heat exchange medium layer, the reaction material layer, and the second heat exchange medium layer each independently include at least five groups of the turbulence components, and adjacent two groups of the turbulence components are staggered; Preferably, the material of the turbulence components includes any one or a combination of at least two of high molecular polymers, ceramics, or metals; Preferably, the shape of the turbulence components includes any one or a combination of at least two of cylindrical, square, or diamond-shaped columns; Preferably, the height of the turbulence components is 100-400 μm; Preferably, the height-to-diameter ratio of the cylindrical turbulence components is (0.2-0.8):1.

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