A device for continuous production of a medical intermediate 3-fluorotoluene diazotization

Abstract

This invention discloses a dedicated apparatus for the continuous production of the pharmaceutical intermediate 3-fluorotoluene via diazotization, relating to the field of organic synthesis and continuous flow reaction equipment technology. It includes a microchannel salt-forming reactor, a tubular diazotization reactor, a continuous centrifuge, a mother liquor concentration unit, a thermal decomposition reactor, and a control system. The tubular diazotization reactor is sequentially arranged along the flow direction with a mixing section, a reaction section, and an online monitoring section. The mixing section has a built-in static mixing element, and the reaction section has multiple independent temperature control jackets on its outer side. The online monitoring section is equipped with an ORP sensor and a temperature sensor. The control system uses ORP and temperature signals to control the feed rate of the diazotization reagent and the temperature of each temperature zone in a closed-loop manner. This invention enables safe, continuous, and efficient production of the diazotization reaction, with advantages such as high yield, high purity, long operating cycle, and low waste liquid and solid waste discharge.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis and continuous flow reaction equipment technology, and more specifically, to a special device for the continuous production of the pharmaceutical intermediate 3-fluorotoluene by diazotization. Background Technology

[0002] 3-Fluorotoluene is an important pharmaceutical intermediate widely used in the synthesis of antidepressants, antitumor drugs, and antiviral drugs. One of its key production steps involves using 3-fluoroaniline as a raw material, which undergoes a diazotization reaction to generate a diazonium salt, followed by reductive dediazotization or a Sandmeyer reaction to convert it into 3-fluorotoluene.

[0003] Diazotization is a strongly exothermic reaction (ΔH ≈ -150 ~ -200 kJ / mol). Diazo salts are sensitive to heat, friction, and impact, and are easily decomposed or even explode. Traditional batch reactor processes have drawbacks such as poor safety, low yield, difficulty in temperature control, insufficient feeding precision, low degree of continuity, and heavy burden of waste liquid treatment. Although some technologies have attempted to use microchannel reactors or tubular reactors for continuous diazotization, existing continuous equipment generally suffers from problems such as pipeline blockage, scaling, and lack of online monitoring, and lacks effective closed-loop control methods, making it difficult to simultaneously meet the requirements of safe, efficient, and clean production. Summary of the Invention

[0004] To overcome the aforementioned deficiencies of the prior art, embodiments of the present invention provide a dedicated continuous production apparatus for the diazotization of the pharmaceutical intermediate 3-fluorotoluene. This apparatus addresses technical problems in the prior art, such as poor safety, low yield, difficulty in temperature control, easy clogging, and lack of online control. It achieves safe, efficient, continuous, and clean production of the diazotization reaction. Through rapid microchannel mixing connected in series with a multi-temperature zone tubular reactor, combined with ORP closed-loop feedback control, it achieves precise feeding of the diazotizing reagent and reaction temperature fluctuations ≤ ±1℃, avoiding local overheating and diazonium salt accumulation, effectively suppressing the risk of decomposition and explosion, and significantly improving production safety. Furthermore, by setting a static mixing element… Enhanced mass transfer and mixing time of <10ms, multi-temperature gradient temperature control suppress side reactions, and the use of N2O3 to replace NaNO2 eliminates the need for sodium introduction, resulting in a 3-fluorotoluene yield of over 97.5% and a purity of over 99.5%, significantly reducing by-products and improving product yield and purity. Finally, the internal PTFE / FFKM coating combined with ultrasonic periodic anti-scaling ensures continuous operation for over 72 hours without clogging. The mother liquor is concentrated and reused, and the pyrolysis residue is used as an adsorbent, reducing wastewater discharge by over 90% and achieving zero solid waste discharge, thus realizing continuous, stable, and clean production and further enhancing the practicality of the device to solve the problems mentioned in the background technology.

[0005] To achieve the above objectives, the present invention provides the following technical solution: a special device for continuous production of diazotization of pharmaceutical intermediate 3-fluorotoluene, comprising a microchannel salt-forming reactor having a first inlet and a second inlet, wherein the first inlet is used to introduce a 3-fluoroaniline solution and the second inlet is used to introduce an acid solution; A tubular diazotization reactor, the inlet of which is connected to the outlet of the microchannel salt-forming reactor, and a third inlet for introducing gaseous diazotization reagent; The tubular diazotization reactor is divided into a mixing section, a reaction section, and an online monitoring section along the material flow direction. The mixing section incorporates a static mixing element; The outer side of the reaction section is provided with multiple independent temperature control jackets to form multiple temperature zones; The online monitoring section is equipped with an oxidation-reduction potential sensor and a temperature sensor; A continuous centrifugal separator, the inlet of which is connected to the outlet of the tubular diazotization reactor; The mother liquor concentration unit has its inlet connected to the liquid phase outlet of the continuous centrifuge, and the concentrated liquid outlet of the mother liquor concentration unit is connected to the second inlet of the microchannel salt-forming reactor. A pyrolysis reactor, the inlet of which is connected to the solid phase outlet of the continuous centrifugal separator; The control system is connected to the redox potential sensor, the temperature sensor, the feed pump for supplying the diazotizing reagent to the third inlet, and the temperature control jackets, respectively, and controls the flow rate of the feed pump and the cooling capacity of each temperature control jacket according to the detection signals of the redox potential sensor and the temperature sensor.

[0006] Preferably, the internal channel hydraulic diameter of the microchannel salt-forming reactor is ≤1mm.

[0007] Preferably, the inner wall of the tubular diazotization reactor is coated with a polytetrafluoroethylene coating or a perfluoroether rubber coating.

[0008] Preferably, an ultrasonic transducer is provided on the outside of the tubular diazotization reactor. The ultrasonic transducer is signal-connected to the control system and is periodically started and stopped by the control system.

[0009] Preferably, the ultrasonic transducer operates at a frequency of 20-40 kHz.

[0010] Preferably, multiple independent temperature control jackets arranged outside the reaction section sequentially form a first temperature zone, a second temperature zone, and a third temperature zone along the material flow direction. The temperature of the first temperature zone is controlled at -2 to 0°C, the temperature of the second temperature zone is controlled at -5 to -3°C, and the temperature of the third temperature zone is controlled at -10 to -6°C.

[0011] Preferably, the mother liquor concentration unit is equipped with an online densitometer or refractometer, which is connected to the control system. When the density of the mother liquor is detected to reach 1.25-1.30 g / cm³, the control system automatically opens the valve of the concentrate outlet.

[0012] Preferably, it further includes a gas-liquid separator, the inlet of which is connected to the outlet of the tubular diazotization reactor, and the liquid phase outlet of which is connected to the inlet of the continuous centrifugal separator.

[0013] Preferably, the system further includes a spray absorption tower and an oil-water separator, wherein the gas inlet of the spray absorption tower is connected to the gas outlet of the pyrolysis reactor, the liquid phase outlet of the spray absorption tower is connected to the inlet of the oil-water separator, and the aqueous phase outlet of the oil-water separator is connected to the mother liquor concentration unit or the acid preparation section.

[0014] Preferably, the pyrolysis reactor is a fluidized bed reactor or a rotary kiln, and its interior is divided into a preheating section, a pyrolysis section and a cooling section in sequence along the material flow direction.

[0015] The technical effects and advantages of this invention are as follows: This invention achieves precise feeding of diazotizing reagents and reaction temperature fluctuations of ≤±1℃ by connecting microchannel rapid mixing in series with a multi-temperature zone tubular reactor and combining it with ORP closed-loop feedback control. This avoids local overheating and diazonium salt accumulation, effectively suppresses the risk of decomposition and explosion, and significantly improves production safety.

[0016] This invention enhances mass transfer by setting up static mixing elements, achieving a mixing time of <10ms. Multi-temperature gradient temperature control suppresses side reactions. Combined with the use of N2O3 to replace NaNO2 to eliminate sodium introduction, the yield of 3-fluorotoluene reaches over 97.5% and the purity over 99.5%, significantly reducing by-products and improving product yield and purity.

[0017] This invention achieves continuous, stable, and clean production by combining an inner wall PTFE / FFKM coating with ultrasonic periodic anti-scaling, allowing for continuous operation for over 72 hours without clogging; the mother liquor is concentrated and reused, and pyrolysis residue is used as an adsorbent, resulting in a waste liquid reduction of over 90% and zero solid waste discharge. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of a special apparatus for the continuous production of the pharmaceutical intermediate 3-fluorotoluene by diazotization according to the present invention. Figure 2 This is a logic block diagram of the control system of the present invention.

[0019] The attached diagram is labeled as follows: A, Microchannel salt-forming reactor; A1, A2, Inlet; A3, Outlet; B, Tubular diazotization reactor; B1, Third inlet; B2, Mixing section; B21, Static mixing element; B3, Reaction section; B31, Temperature control jacket; B4, Online monitoring section; B41, ORP sensor; B42, Temperature sensor; B5, Coating; B6, Ultrasonic transducer; C, Gas-liquid separator; D, Continuous centrifuge; E, Mother liquor concentration unit; E1, Densitometer; F, Thermal decomposition reactor; G, Spray absorption tower; H, Oil-water separator; I, Distillation column; J, Control system. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] As attached Figures 1 to 2 The apparatus shown is a dedicated device for the continuous production of 3-fluorotoluene, a pharmaceutical intermediate, by diazotization. It includes a microchannel salt-forming reactor A, which has a first inlet A1 and a second inlet A2. The first inlet A1 is connected to a 3-fluoroaniline storage tank via a metering pump, and the second inlet A2 is connected to a fluoroboric acid solution storage tank via a metering pump. The hydraulic diameter of the internal channels of the microchannel salt-forming reactor A is ≤1mm (preferably 0.5~0.8mm), and the total length of the channels is ≥500mm. Its outlet A3 is connected to the inlet of a tubular diazotization reactor B.

[0022] The tubular diazotization reactor B is a slender tube with an inner diameter of 3-6 mm and a total length of 6-12 m. It is divided into a mixing section B2, a reaction section B3, and an online monitoring section B4 along the material flow direction.

[0023] The mixing section B2 is 0.5~1.0m long and has a built-in static mixing element B21. The static mixing element is a spiral or serrated metal sheet with an aspect ratio ≥10. The mixing section is also equipped with a third inlet B1 for introducing gaseous nitrogen trioxide (N2O3).

[0024] The reaction section B3 is 4-8m long and is fitted with multiple independent temperature-controlled jackets B31. In this embodiment, three temperature-controlled jackets are provided, forming a first temperature zone, a second temperature zone, and a third temperature zone along the material flow direction, respectively. Each temperature-controlled jacket is filled with circulating coolant (such as an aqueous solution of ethylene glycol) and is equipped with an independent flow regulating valve.

[0025] The online monitoring section B4 is 0.2~0.5m long and is equipped with an oxidation-reduction potential sensor B41 (model: Mettler Toledo InPro3250i) and a temperature sensor B42 (Pt100 platinum resistance thermometer).

[0026] The inner wall of the tubular diazotization reactor B is coated with a polytetrafluoroethylene coating B5 (thickness 20~50μm). Multiple ultrasonic transducers B6 (operating frequency 20~40kHz, power 50W) are installed at intervals on the outside of the reaction section B3 and the online monitoring section B4. The ultrasonic transducers B6 are connected to the control system J via signals.

[0027] The gas-liquid separator C has its inlet connected to the outlet of the tubular diazotization reactor B. The top of the gas-liquid separator C has a gas phase outlet C1 connected to the tail gas treatment system, and the bottom liquid phase outlet C2 is connected to the continuous centrifugal separator D.

[0028] The continuous centrifugal separator D uses a horizontal screw discharge centrifuge, such as model LW250. Its liquid phase outlet D1 is connected to the mother liquor concentration unit E, and its solid phase outlet D2 is connected to the thermal decomposition reactor F.

[0029] The mother liquor concentration unit E is an evaporator with a heating jacket and an online density meter E1 (model: Endress+Hauser FTM50). The concentrate outlet E2 is connected to the second inlet A2 of the microchannel salt formation reactor A through pipes and valves; the wastewater outlet E3 is connected to the plant wastewater treatment station or acid preparation section.

[0030] The thermal decomposition reactor F is a fluidized bed reactor, which is divided into a preheating section (300~400℃), a pyrolysis section (550~650℃) and a cooling section (below 100℃) in sequence along the material flow direction. Its gas outlet F1 is connected to the spray absorption tower G, and the solid slag outlet F2 is used to collect carbonization residue.

[0031] The spray absorption tower G is equipped with a spray distributor inside the tower. The spray liquid is a 10~20wt% hydrofluoric acid solution. The liquid phase outlet at the bottom of the tower is connected to the oil-water separator H.

[0032] The oil-water separator H is a gravity stratification tank. The oil phase outlet H1 is connected to the distillation column I, and the water phase outlet H2 is connected to the mother liquor concentration unit E or the acid preparation section.

[0033] Distillation column I has 20 theoretical plates, a top reflux ratio of 2:1, a top temperature of 80℃, and a bottom temperature of 105℃. It is used to purify 3-fluorotoluene.

[0034] The control system J adopts a PLC (Programmable Logic Controller, Siemens S7-1200). Its input terminals are electrically connected to the redox potential sensor B41, the temperature sensor B42, and the online density meter E1, respectively. Its output terminals are electrically connected to each metering pump, the coolant regulating valve of the temperature control jacket B31, the power switch of the ultrasonic transducer B6, and the valve of the concentrate outlet E2, respectively.

[0035] like Figure 2 As shown, control system J executes the following control logic: ORP closed-loop control: The target ORP value range is set to 500~800mV (relative to the Ag / AgCl reference electrode). The redox potential sensor B41 detects the ORP value of the reaction solution in real time and feeds it back to the PLC. The PLC adjusts the speed of the N2O3 feed pump through a PID algorithm (proportional coefficient Kp=0.8, integral time Ti=30s, derivative time Td=5s) to stabilize the ORP value near the set point.

[0036] Temperature cascade control: Temperature sensors B42 in three temperature zones detect the actual temperature of each zone. The PLC compares the measured values ​​with the set values ​​of each temperature zone (first temperature zone -2~0℃, second temperature zone -5~-3℃, third temperature zone -10~-6℃) and adjusts the coolant flow rate of each temperature control jacket B31 through PID algorithm to achieve precise temperature control.

[0037] Ultrasonic anti-scaling control: The PLC has a built-in timer that automatically starts the ultrasonic transducer B6 for 30 seconds every 5 minutes of operation, with the frequency sweeping within the range of 20~40kHz.

[0038] Mother liquor reuse control: The online density meter E1 detects the liquid density in the mother liquor concentration unit E in real time. When the density reaches 1.25~1.30g / cm³, the PLC automatically opens the valve of the concentrate outlet E2 to send the concentrate back to the second inlet A2 of the microchannel salt formation reactor A.

[0039] Working process: 3-fluoroaniline solution and 25wt% fluoroboric acid solution are introduced into the microchannel salt formation reactor A through the first inlet A1 and the second inlet A2 at a set flow rate (molar ratio 1:1.05). They rapidly mix at 10~20℃ to form ammonium salt, with a residence time of <10 seconds. The ammonium salt solution then enters the mixing section B2 of the tubular diazotization reactor B. Simultaneously, N2O3 gas (self-pressurized feed, storage tank temperature -30℃, pressure ≤0.03MPa) enters through the third inlet B1, instantaneously mixing with the ammonium salt solution in the static mixing element B21 (mixing time <10ms). The mixture then enters the reaction section B3, where it undergoes a three-temperature gradient reaction. The diazotization reaction is completed under cooling (total residence time 1-5 minutes). After being monitored by online monitoring section B4, the reaction liquid enters the gas-liquid separator C, where unreacted gas is separated. The liquid phase enters the continuous centrifugal separator D, yielding wet diazonium salt (solid phase) and mother liquor (liquid phase). The mother liquor enters the mother liquor concentration unit E for concentration and reuse. The wet diazonium salt enters the thermal decomposition reactor F, where it is pyrolyzed at 550-650℃ to generate 3-fluorotoluene gas and carbonized residue. The gas enters the spray absorption tower G, where it is absorbed and cooled by hydrofluoric acid solution. Then, it enters the oil-water separator H for stratification. The oil phase enters the distillation tower I for distillation to obtain 3-fluorotoluene product, and the aqueous phase is reused for acid preparation. The carbonized residue is used as an adsorbent for wastewater treatment.

[0040] In Example 1, the above-described device is preferably used, and the specific parameters are as follows: Microchannel salt-forming reactor A: hydraulic diameter 0.8 mm, length 600 mm; 3-fluoroaniline feed flow rate 1.6 g / min, 25 wt% fluoroboric acid solution feed flow rate 9.5 g / min, salt-forming temperature 15 ℃.

[0041] Tubular diazotization reactor B: inner diameter 4mm, total length 8m; mixing section length 0.8m (spiral static mixer); three temperature zones in the reaction section are 0℃, -3℃, and -7℃ respectively; N2O3 feed flow rate 0.38g / min (self-pressurized, storage tank -30℃); total residence time 3 minutes.

[0042] Control system settings: ORP target value 650mV, PID parameters Kp=0.8, Ti=30s, Td=5s; ultrasonic waves start for 30 seconds every 5 minutes, frequency 30kHz.

[0043] Thermal decomposition reactor F: fluidized bed, temperature 620℃, feed rate 2.2g / min.

[0044] Spray absorption tower G: 15wt% hydrofluoric acid solution is circulated and sprayed.

[0045] Distillation column I: Top temperature 80℃, bottom temperature 105℃, reflux ratio 2:1.

[0046] Results: After 96 hours of continuous operation without blockage, the collected product was analyzed by gas chromatography (GC) with internal standard method. The content of the byproduct 3-fluorophenol was 0.12%, and azo compounds were not detected.

[0047] Example 2: Basically the same as Example 1, except that: The hydraulic diameter of the microchannel salt-forming reactor A is 0.5 mm.

[0048] The three temperature zones are -2℃, -5℃, and -8℃, respectively.

[0049] N2O3 feed flow rate: 0.42 g / min.

[0050] ORP target value: 700mV.

[0051] The ultrasonic frequency sweep is 20~40kHz, and it starts for 25 seconds every 4 minutes.

[0052] Results: After running continuously for 84 hours, the operation was stopped, and the content of the byproduct 3-fluorophenol was 0.09%.

[0053] Example 3: Basically the same as Example 1, except that: The concentration of the fluoroboric acid solution is 20wt%.

[0054] The three temperature zones are -1℃, -4℃, and -9℃, respectively.

[0055] The temperature of the thermal decomposition reactor F is 650℃.

[0056] Results: The test was stopped after 72 hours of continuous operation. The content of the byproduct 3-fluorophenol was 0.18%.

[0057] Comparative Example: Using the traditional batch reactor process: 500 mL of 25 wt% fluoroboric acid solution was added to a 2 L jacketed glass reactor and cooled to 0-5 °C with stirring. 3-fluoroaniline (total 80 g) was slowly added dropwise, and the dropping rate was controlled so that the temperature did not exceed 5 °C. After the addition was complete, sodium nitrite solution (44 g of sodium nitrite dissolved in 80 mL of water) was added dropwise. The reaction was maintained at 0-5 °C for 1 hour. The reaction solution was filtered, and the filter cake was washed with a small amount of cold water to obtain a wet diazonium salt. Subsequent thermal decomposition and distillation were the same as in Example 1.

[0058] Results: Temperature fluctuation during the reaction was ±6.2℃. The content of 3-fluorophenol in the byproducts was 1.2%, and the content of azo compounds was 0.3%. Approximately 8 tons of sodium-containing wastewater and approximately 85 kg of solid waste were generated per ton of product. During continuous production, the reaction vessel needs to be cleaned for each batch.

[0059] As can be seen from Examples 1-3 and the comparative examples above, the device of the present invention significantly improves the yield and purity of 3-fluorotoluene through the synergistic effect of multiple technical means such as microchannel rapid mixing, multi-temperature zone precise temperature control, ORP closed-loop feedback, ultrasonic anti-scaling and coating anti-adhesion. At the same time, it achieves long-term continuous and stable operation, reduces waste liquid and solid waste discharge, and achieves unexpected technical effects.

[0060] Finally, the following points should be noted: First, in the description of this application, it should be noted that, unless otherwise specified and limited, the terms "installation", "connection", and "linkage" should be interpreted broadly, and can be mechanical or electrical connections, or internal connections between two components, or direct connections. "Up", "down", "left", "right", etc. are only used to indicate relative positional relationships. When the absolute position of the described object changes, the relative positional relationship may change. Secondly: The accompanying drawings of the embodiments disclosed in this invention only involve the structures involved in the embodiments disclosed in this invention. Other structures can refer to the general design. In the absence of conflict, the same embodiment and different embodiments of this invention can be combined with each other. In conclusion, the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A dedicated apparatus for the continuous production of the pharmaceutical intermediate 3-fluorotoluene via diazotization, characterized in that, include: A microchannel salt-forming reactor (A) has a first inlet (A1) and a second inlet (A2), the first inlet (A1) being used to introduce a 3-fluoroaniline solution and the second inlet (A2) being used to introduce an acid solution; A tubular diazotization reactor (B) has its inlet connected to the outlet (A3) of the microchannel salt-forming reactor (A) and a third inlet (B1) for introducing gaseous diazotization reagent; The tubular diazotization reactor (B) is divided into a mixing section (B2), a reaction section (B3), and an online monitoring section (B4) along the material flow direction. The mixing section (B2) has a built-in static mixing element (B21). The outer side of the reaction section (B3) is provided with multiple independent temperature control jackets (B31) to form multiple temperature zones; The online monitoring section (B4) is equipped with an oxidation-reduction potential sensor (B41) and a temperature sensor (B42). A continuous centrifugal separator (D) has its inlet connected to the outlet of the tubular diazotization reactor (B); The mother liquor concentration unit (E) has its inlet connected to the liquid phase outlet (D1) of the continuous centrifuge (D), and the concentrated liquid outlet (E2) of the mother liquor concentration unit (E) is connected to the second inlet (A2) of the microchannel salt-forming reactor (A). The inlet of the pyrolysis reactor (F) is connected to the solid outlet (D2) of the continuous centrifugal separator (D); The control system (J) is connected to the redox potential sensor (B41), the temperature sensor (B42), the feed pump for supplying diazotizing reagent to the third inlet (B1), and each of the temperature control jackets (B31) respectively, and controls the flow rate of the feed pump and the cooling capacity of each of the temperature control jackets (B31) according to the detection signals of the redox potential sensor (B41) and the temperature sensor (B42).

2. The special apparatus for continuous production of the pharmaceutical intermediate 3-fluorotoluene diazotization according to claim 1, characterized in that, The internal channel hydraulic diameter of the microchannel salt-forming reactor (A) is ≤1mm.

3. The special apparatus for continuous production of the pharmaceutical intermediate 3-fluorotoluene diazotization according to claim 1, characterized in that, The inner wall of the tubular diazotization reactor (B) is coated with a polytetrafluoroethylene coating or a perfluoroether rubber coating (B5).

4. A dedicated apparatus for continuous production of the pharmaceutical intermediate 3-fluorotoluene by diazotization according to claim 1, characterized in that, An ultrasonic transducer (B6) is installed on the outside of the tubular diazotization reactor (B). The ultrasonic transducer (B6) is connected to the control system (J) and is periodically started and stopped by the control system (J).

5. A dedicated apparatus for continuous production of the pharmaceutical intermediate 3-fluorotoluene diazotization according to claim 4, characterized in that, The ultrasonic transducer (B6) operates at a frequency of 20-40kHz.

6. A dedicated apparatus for continuous production of the pharmaceutical intermediate 3-fluorotoluene by diazotization according to claim 1, characterized in that, Multiple independent temperature control jackets (B31) set outside the reaction section (B3) sequentially form a first temperature zone, a second temperature zone, and a third temperature zone along the material flow direction. The temperature of the first temperature zone is controlled at -2~0℃, the temperature of the second temperature zone is controlled at -5~-3℃, and the temperature of the third temperature zone is controlled at -10~-6℃.

7. A dedicated apparatus for continuous production of the pharmaceutical intermediate 3-fluorotoluene via diazotization according to claim 1, characterized in that, The mother liquor concentration unit (E) is equipped with an online densitometer or refractometer (E1). The online densitometer or refractometer (E1) is connected to the control system (J) via a signal. When the density of the mother liquor is detected to reach 1.25-1.30 g / cm³, the control system (J) automatically opens the valve of the concentrate outlet (E2).

8. A dedicated apparatus for continuous production of the pharmaceutical intermediate 3-fluorotoluene by diazotization according to claim 1, characterized in that, It also includes a gas-liquid separator (C), the inlet of which is connected to the outlet of the tubular diazotization reactor (B), and the liquid phase outlet of which is connected to the inlet of the continuous centrifugal separator (D).

9. A dedicated apparatus for continuous production of the pharmaceutical intermediate 3-fluorotoluene by diazotization according to claim 1, characterized in that, It also includes a spray absorption tower (G) and an oil-water separator (H). The gas inlet of the spray absorption tower (G) is connected to the gas outlet (F1) of the pyrolysis reactor (F). The liquid phase outlet of the spray absorption tower (G) is connected to the inlet of the oil-water separator (H). The aqueous phase outlet (H2) of the oil-water separator (H) is connected to the mother liquor concentration unit (E) or the acid mixing section.

10. A dedicated apparatus for continuous production of the pharmaceutical intermediate 3-fluorotoluene by diazotization according to claim 1, characterized in that, The pyrolysis reactor (F) is a fluidized bed reactor or a rotary kiln, and its interior is divided into a preheating section, a pyrolysis section and a cooling section in sequence along the material flow direction.

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