Continuous production system and production method for 1-(4-chlorophenyl)-3-pyrazolol

Abstract

The present invention belongs to the technical field of organic compound synthesis, and specifically discloses a continuous production system and a production method for 1-(4-chlorophenyl)-3-pyrazolol. It is used to solve the problems of low production efficiency, high operation cost and danger, and large wastewater discharge in the traditional batch hydrogen peroxide oxidation process. The production system includes a raw material premixing tank, a transfer pump, an air gas source, an ejector, a reaction unit, a pH adjustment tank, a continuous filter, a temporary storage tank, a continuous dryer and an ion resin exchanger; the reaction unit includes a plurality of static mixing tube-type continuous flow reactors connected in series, which are internally provided with static mixing elements and externally provided with heat exchange jackets; the outer side walls of the raw material premixing tank and the pH adjustment tank are both provided with heat exchange jackets or coils; the ion resin exchanger is provided with a backwash port. The present invention realizes full-process continuous production, realizes green and safe preparation, and improves production efficiency as well as product yield and purity.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic compound synthesis, and particularly relates to a continuous production system and a production method for 1-(4-chlorophenyl)-3-pyrazolol. Background Art

[0002] As an important intermediate for synthetic drugs in the fields of medicine, chemical industry, and pesticides, 1-(4-chlorophenyl)-3-pyrazolol has a very high market share. The main preparation route of 1-(4-chlorophenyl)-3-pyrazolol is the oxidative synthesis of 1-(4-chlorophenyl)pyrazolidin-3-one. The traditional production method of 1-(4-chlorophenyl)-3-pyrazolol is mainly based on the process of oxidizing 1-(4-chlorophenyl)pyrazolidin-3-one with hydrogen peroxide to synthesize 1-(4-chlorophenyl)-3-pyrazolol. This process belongs to a dangerous process, the reaction process is difficult to control, the product is easily over-oxidized, and it has defects such as low yield, poor quality, long reaction time, high production cost, great potential safety hazards, and large wastewater discharge.

[0003] The existing production equipment for 1-(4-chlorophenyl)-3-pyrazolol is mainly intermittent reaction kettles, and the production processes such as reaction, filtration, and drying are all mainly intermittent operations. The equipment occupies a large area, has high operating costs, and low automation level. Therefore, there is an urgent need to introduce a new type of continuous production method for 1-(4-chlorophenyl)-3-pyrazolol to realize the industrial upgrading of the preparation of 1-(4-chlorophenyl)-3-pyrazolol with green safety. Summary of the Invention

[0004] An object of the present invention is to provide a continuous production system for 1-(4-chlorophenyl)-3-pyrazolol, which effectively solves the problems of low production efficiency, high operating costs and high risk, and large wastewater discharge in the traditional intermittent hydrogen peroxide oxidation process.

[0005] To solve the above technical problems, the technical solution adopted by the present invention is: a continuous production system for 1-(4-chlorophenyl)-3-pyrazolol, which includes a raw material premixing tank, a delivery pump, an air gas source, an ejector, a reaction unit, a pH adjustment tank, a continuous filter, a temporary storage tank, a continuous dryer, and an ion resin exchanger. The reaction unit includes a plurality of static mixing tube-type continuous flow reactors connected in series. The ion resin exchanger includes an exchanger inlet at the top, a backwash port at the lower part, a wastewater discharge port at the bottom, and a flushing liquid outlet at the upper part.

[0006] The outlet of the raw material premixing tank is connected to the inlet of the transfer pump. The outlet of the transfer pump is connected to the inlet of the continuous phase pipeline of the ejector. The outlet of the air gas source is connected to the inlet of the discrete phase pipeline of the ejector. The outlet of the ejector is connected to the inlet of the reaction unit. The outlet of the reaction unit is connected to the inlet of the pH adjustment tank. The outlet of the pH adjustment tank is connected to the inlet of the continuous filter. The liquid phase outlet of the continuous filter is connected to the inlet of the temporary storage tank. The solid phase outlet of the continuous filter is connected to the inlet of the continuous dryer. The outlet of the temporary storage tank is connected to the exchanger inlet of the ion resin exchanger. The flushing liquid outlet of the ion resin exchanger is connected to the inlet of the raw material premixing tank.

[0007] Further, there are multiple raw material premixing tanks, which are arranged in parallel. During the raw material premixing process, continuous output of the premixed raw materials is achieved through the switching cooperation among the raw material premixing tanks.

[0008] Further, a heat exchange jacket or coil is provided on the outer side wall of the raw material premixing tank, and the coil can also be arranged inside the tank body of the raw material premixing tank.

[0009] Further, static mixing elements are provided inside the static mixing tube type continuous flow reactor, and a heat exchange jacket is provided outside the static mixing tube type continuous flow reactor.

[0010] Further, there are multiple pH adjustment tanks, which are arranged in parallel. During the pH adjustment process, continuous output of the suspension is achieved through the switching cooperation among the pH adjustment tanks. A heat exchange jacket or coil is provided on the outer side wall of the pH adjustment tank, and the coil can also be arranged inside the tank body of the pH adjustment tank.

[0011] Further, the raw material premixing tank is used to stir and mix the raw materials into a uniform premixed raw material; the transfer pump is used to transport the premixed raw material to the static mixing tubular continuous flow reactor in the reaction unit through the continuous phase pipeline of the ejector; the air gas source is used to provide the air required in the reaction process; the ejector is used to inject air into the reaction pipeline for co-current mixing with the premixed raw material; the static mixing tubular continuous flow reactor is used to carry out the oxidation reaction process of catalytically oxidizing 1-(4-chlorophenyl)pyrazolidin-3-one with oxygen in the air to synthesize 1-(4-chlorophenyl)-3-pyrazolol; the pH adjustment tank is used to precipitate the liquid-phase 1-(4-chlorophenyl)-3-pyrazolol in the form of solid phase through pH adjustment to form a suspension; the continuous filter is used for continuous solid-liquid separation of the suspension; the temporary storage tank is used for temporary storage of the mother liquor after filtration; the continuous dryer is used for continuous drying of the solid-phase 1-(4-chlorophenyl)-3-pyrazolol; the ion resin exchanger is used to recover the transition metal ion catalyst, and at the same time, the ion resin exchanger is used to return the liquid-phase catalyst recovered after backwashing to the raw material premixing tank.

[0012] Another object of the present invention is to provide a continuous production method of 1-(4-chlorophenyl)-3-pyrazolol, which is applied to the continuous production system of 1-(4-chlorophenyl)-3-pyrazolol described in the above embodiments, and includes the following steps: S1. Put 1-(4-chlorophenyl)pyrazolidin-3-one, inorganic base, transition metal ion catalyst and water into the raw material premixing tank, stir and mix them, and control the temperature at 20-50 °C to form a premixed raw material.

[0013] Among them, the molar ratio of 1-(4-chlorophenyl)pyrazolidin-3-one to the inorganic base is 1:1.1-1.8, the molar ratio of 1-(4-chlorophenyl)pyrazolidin-3-one to the transition metal ion catalyst is 1:0.001-0.02, and the mass fraction of 1-(4-chlorophenyl)pyrazolidin-3-one is 10%-40%.

[0014] S2. Through the transfer pump, the premixed raw material is transported to the static mixing tubular continuous flow reactor in the reaction unit through the continuous phase pipeline of the ejector, and the air from the air gas source is injected into the static mixing tubular continuous flow reactor in the reaction unit through the discrete phase pipeline by using the ejector.

[0015] 1-(4-chlorophenyl)pyrazolidin-3-one in the premixed raw material and oxygen in the air carry out an oxidation reaction in the static mixing tubular continuous flow reactor to obtain liquid-phase 1-(4-chlorophenyl)-3-pyrazolol.

[0016] The molar ratio of 1-(4-chlorophenyl)pyrazolidin-3-one to oxygen in the air is 1:0.55 - 0.85, the reaction temperature is 40 - 90 °C, the reaction pressure is 0.1 - 1.6 MPa, and the total residence time of the premixed raw materials in the reaction unit is 0.6 - 10 min.

[0017] S3. The liquid-phase 1-(4-chlorophenyl)-3-pyrazolol generated by the reaction enters the pH adjustment tank, and hydrochloric acid is introduced into the pH adjustment tank to adjust the pH to 3 - 6. The temperature in the pH adjustment tank is controlled at 30 - 50 °C, and 1-(4-chlorophenyl)-3-pyrazolol precipitates in the form of a solid phase. The stirring time is 5 - 30 min; then it is cooled to 20 - 30 °C to form a suspension.

[0018] S4. The suspension is fed into a continuous filter for continuous solid-liquid separation, separated into the solid phase of 1-(4-chlorophenyl)-3-pyrazolol and the mother liquor.

[0019] S5. The separated solid phase of 1-(4-chlorophenyl)-3-pyrazolol enters a continuous dryer, and the drying temperature is 60 - 95 °C. After drying, the product of 1-(4-chlorophenyl)-3-pyrazolol is obtained.

[0020] S6. The separated mother liquor continuously enters the storage tank. When the mother liquor in the storage tank reaches the volume upper limit of the storage tank, discharging operation is carried out. The mother liquor enters the ion resin exchanger, and the transition metal ion catalyst in the mother liquor is adsorbed by the ion resin in the ion resin exchanger. The mother liquor after adsorption is continuously discharged in the form of wastewater.

[0021] The discharging speed of the storage tank is greater than the feeding speed of the storage tank. The mother liquor in the storage tank gradually decreases and stops discharging after reaching the volume lower limit. Flushing liquid is introduced through the backwashing port of the ion resin exchanger, so that the transition metal ion catalyst is desorbed from the ion resin and returns to the raw material premixing tank with the flushing liquid.

[0022] Furthermore, in step S1, there are two raw material premixing tanks, namely the first raw material premixing tank and the second raw material premixing tank. While the first raw material premixing tank outputs the premixed raw materials, the premixing operation of the raw materials is carried out in the second raw material premixing tank; after the output of the premixed raw materials in the first raw material premixing tank is completed, the premixing operation of the raw materials is carried out again, and at the same time, the second raw material premixing tank is started to output the premixed raw materials; the continuous transportation process of the premixed raw materials is realized through the switching cooperation of the first raw material premixing tank and the second raw material premixing tank.

[0023] Further, in step S3, there are two pH adjustment tanks, namely the first pH adjustment tank and the second pH adjustment tank. When the first pH adjustment tank performs the operations of pH adjustment to precipitate solid sediment and discharge the suspension, the liquid phase of 1-(4-chlorophenyl)-3-pyrazolol is conveyed into the second pH adjustment tank; when the discharge of the suspension in the first pH adjustment tank is completed, the liquid phase of 1-(4-chlorophenyl)-3-pyrazolol is re-input into the first pH adjustment tank, and at the same time, the liquid phase of 1-(4-chlorophenyl)-3-pyrazolol stops entering the second pH adjustment tank, and the operations of pH adjustment to precipitate solid sediment and discharge the suspension are carried out in the second pH adjustment tank; the continuous post-treatment process of the suspension is realized through the switching cooperation of the first pH adjustment tank and the second pH adjustment tank.

[0024] Further, in step S6, while the backwashing operation is being carried out, the separated mother liquor continuously enters the temporary storage tank. When the volume upper limit in the temporary storage tank is reached again, step S6 is repeated to realize the continuous treatment of the separated mother liquor.

[0025] Compared with the prior art, the beneficial technical effects of the present invention are as follows: (1) The present invention relies on a static mixing tubular continuous flow reactor, a continuous filter and a continuous dryer to realize the full-process continuous production of the synthesis, filtration and drying of 1-(4-chlorophenyl)-3-pyrazolol, greatly improving the production efficiency, effectively reducing the floor area of the equipment, reducing the operation cost and operation risk, and realizing the industrial upgrading of the green and safe preparation of 1-(4-chlorophenyl)-3-pyrazolol.

[0026] (2) The present invention adopts a production method of catalytic air oxidation of 1-(4-chlorophenyl)pyrazolidin-3-one with transition metal ions to replace the traditional hydrogen peroxide oxidation process, significantly reducing the production cost and process risk, reducing the generation and discharge of wastewater, and realizing green and safe production.

[0027] (3) The present invention uses a static mixing tubular continuous flow reactor to replace the traditional batch kettle reaction. By setting static mixing elements with strong mixing effect and low resistance in the static mixing tubular continuous flow reactor, the gas-liquid two-phase mass transfer effect in the pipe is effectively strengthened, the residence time in the reactor is accurately controlled, the reaction efficiency and process controllability are improved, the occurrence of over-oxidation side reactions is avoided, and the production of 1-(4-chlorophenyl)-3-pyrazolol with high yield and high purity is realized.

[0028] (4) The present invention realizes the recovery and reuse of the liquid-phase transition metal ion catalyst through an ion resin exchanger, reduces the salt content in the wastewater and the wastewater treatment pressure, and effectively reduces the production cost. Description of the Drawings

[0029] Figure 1 It is a schematic connection structure diagram of the continuous production system of 1-(4-chlorophenyl)-3-pyrazolol in Example 1.

[0030] Description of reference numerals: First raw material premixing tank - 1; Second raw material premixing tank - 2; First transfer pump - 3; Second transfer pump - 4; Air gas source - 5; Ejector - 6; First pH adjustment tank - 7; Second pH adjustment tank - 8; Continuous filter - 9; Temporary storage tank - 10; Continuous dryer - 11; Ion resin exchanger - 12; Static mixing tube type continuous flow reactor - 13; Exchanger inlet - 14; Backwashing port - 15; Waste water discharge port - 16; Flushing liquid outlet - 17; 1-(4-chlorophenyl)-3-pyrazolol product outlet - 18. Detailed implementation mode

[0031] Example 1: As Figure 1 shown, the continuous production system of 1-(4-chlorophenyl)-3-pyrazolol includes a first raw material premixing tank 1, a second raw material premixing tank 2, a first transfer pump 3, a second transfer pump 4, an air gas source 5, an ejector 6, a reaction unit, a first pH adjustment tank 7, a second pH adjustment tank 8, a continuous filter 9, a temporary storage tank 10, a continuous dryer 11 and an ion resin exchanger 12.

[0032] The reaction unit includes three static mixing tube type continuous flow reactors 13 connected in series. Static mixing elements are provided inside the static mixing tube type continuous flow reactor 13, and a heat exchange jacket is provided outside the static mixing tube type continuous flow reactor 13. Heat exchange jackets or coils are provided on the outer side walls of the first raw material premixing tank 1, the second raw material premixing tank 2, the first pH adjustment tank 7 and the second pH adjustment tank 8, and the coils can also be provided inside the tanks of the first raw material premixing tank 1, the second raw material premixing tank 2, the first pH adjustment tank 7 and the second pH adjustment tank 8. The ion resin exchanger 12 includes an exchanger inlet 14 at the top, a backwashing port 15 at the lower part, a waste water discharge port 16 at the bottom and a flushing liquid outlet 17 at the upper part.

[0033] The outlet of the first raw material premixing tank 1 is connected to the inlet of the first transfer pump 3, the outlet of the second raw material premixing tank 2 is connected to the inlet of the second transfer pump 4, the outlets of the first transfer pump 3 and the second transfer pump 4 are both connected to the inlet of the continuous phase pipeline of the ejector 6, the outlet of the air gas source 5 is connected to the inlet of the discrete phase pipeline of the ejector 6, and the outlet of the ejector 6 is connected to the inlet of the reaction unit.

[0034] The outlet of the reaction unit is connected to the inlets of the first pH adjustment tank 7 and the second pH adjustment tank 8. The outlets of the first pH adjustment tank 7 and the second pH adjustment tank 8 are both connected to the inlet of the continuous filter 9. The liquid phase outlet of the continuous filter 9 is connected to the inlet of the temporary storage tank 10. The solid phase outlet of the continuous filter 9 is connected to the inlet of the continuous dryer 11. The outlet of the temporary storage tank 10 is connected to the exchanger inlet 14 of the ion resin exchanger 12. The flushing liquid outlet 17 of the ion resin exchanger 12 is connected to the inlet of the first raw material premixing tank 1.

[0035] Both the first raw material premixing tank 1 and the second raw material premixing tank 2 are used to stir and mix the raw materials into a uniform premixed raw material; both the first transfer pump 3 and the second transfer pump 4 are used to transport the premixed raw material through the continuous phase pipeline of the ejector 6 to the static mixing tubular continuous flow reactor 13 of the reaction unit; the air gas source 5 is used to provide the air required for the reaction process; the ejector 6 is used to eject air into the reaction pipeline for co-current mixing with the premixed raw material; the static mixing tubular continuous flow reactor 13 is used to carry out the oxidation reaction process of catalytically oxidizing 1-(4-chlorophenyl)pyrazolidin-3-one with oxygen in the air to synthesize 1-(4-chlorophenyl)-3-pyrazolol; both the first pH adjustment tank 7 and the second pH adjustment tank 8 are used to precipitate the oxidized synthesized liquid phase 1-(4-chlorophenyl)-3-pyrazolol in the form of solid phase precipitation through pH adjustment to form a suspension; the continuous filter 9 is used for continuous solid-liquid separation of the suspension; the temporary storage tank 10 is used for temporary storage of the mother liquor after filtration; the continuous dryer 11 is used for continuous drying of the solid phase 1-(4-chlorophenyl)-3-pyrazolol; the ion resin exchanger 12 is used to recover the transition metal ion catalyst, and at the same time, the ion resin exchanger 12 is used to return the liquid phase catalyst recovered after backwashing to the first raw material premixing tank 1.

[0036] Example 2: A continuous production method of 1-(4-chlorophenyl)-3-pyrazolol, applied to the continuous production system of 1-(4-chlorophenyl)-3-pyrazolol described in Example 1, includes the following steps: (1) Add 24 L of water to the first raw material premixing tank 1 and the second raw material premixing tank 2 respectively, and then slowly add 852.8 g of sodium hydroxide, 4136.8 g of 1-(4-chlorophenyl)pyrazolidin-3-one and 40 g of ferric chloride under stirring conditions, and stir evenly at a temperature of 35 °C to form a premixed raw material.

[0037] (2) Start the first transfer pump 3 to transport the premixed raw material in the first raw material premixing tank 1 through the continuous phase pipeline of the ejector 6 to the static mixing tubular continuous flow reactor 13 in the reaction unit; while starting the first transfer pump 3, start the air gas source 5 to eject air into the static mixing tubular continuous flow reactor 13 in the reaction unit through the discrete phase pipeline of the ejector 6.

[0038] After the premixed raw materials in the first raw material premixing tank 1 are completely transported, the first transfer pump 3 is closed, and the second transfer pump 4 is started to continue transporting the premixed raw materials in the second raw material premixing tank 2. The first raw material premixing tank 1 repeats the charging and stirring process to ensure the continuous transportation of the premixed raw materials.

[0039] 1-(4-Chlorophenyl)pyrazolidin-3-one in the premixed raw materials undergoes an oxidation reaction with oxygen in the air in the static mixing tubular continuous flow reactor 13. The molar ratio of 1-(4-chlorophenyl)pyrazolidin-3-one to oxygen in the air in the static mixing tubular continuous flow reactor 13 is controlled to be 1:0.65, and the reaction pressure is 0.6 MPa. The total residence time of the premixed raw materials in the reaction unit is 1.2 min, and the reaction temperature is controlled at 50 °C by using the heat exchange jacket of the static mixing tubular continuous flow reactor 13.

[0040] (3) The liquid-phase 1-(4-chlorophenyl)-3-pyrazolol obtained from the oxidation reaction is continuously discharged from the outlet of the static mixing tubular continuous flow reactor 13 and first input into the first pH adjustment tank 7. After reaching the target liquid level, the input is stopped. Hydrochloric acid is introduced into the first pH adjustment tank 7 to adjust the pH to 5, and the temperature in the tank is controlled at 50 °C. After stirring for 10 min, the liquid-phase 1-(4-chlorophenyl)-3-pyrazolol completely precipitates in the form of a solid phase. The temperature is lowered to 20 - 30 °C by using the heat exchange jacket of the first pH adjustment tank 7 to form a suspension.

[0041] (4) The suspension in the first pH adjustment tank 7 is transported to the continuous filter 9 for continuous solid-liquid separation, which is divided into the solid phase of 1-(4-chlorophenyl)-3-pyrazolol and the mother liquor.

[0042] In step (3), when the input of the liquid-phase 1-(4-chlorophenyl)-3-pyrazolol to the first pH adjustment tank 7 stops, the input of the liquid-phase 1-(4-chlorophenyl)-3-pyrazolol to the second pH adjustment tank 8 starts. In step (4), after the suspension in the first pH adjustment tank 7 is emptied, the second pH adjustment tank 8 repeats the pH adjustment and continuous filtration operations in steps (3) and (4). The pH adjustment and continuous filtration operation time in the first pH adjustment tank 7 matches the input time of the liquid-phase 1-(4-chlorophenyl)-3-pyrazolol in the second pH adjustment tank 8. The continuous post-treatment of the liquid-phase 1-(4-chlorophenyl)-3-pyrazolol is ensured through the switching cooperation between the first pH adjustment tank 7 and the second pH adjustment tank 8.

[0043] (5) The solid-phase outlet of the continuous filter 9 is connected to the inlet of the continuous dryer 11. The separated solid-phase 1-(4-chlorophenyl)-3-pyrazolol enters the continuous dryer 11, and the drying temperature is 70 °C. After drying, it is continuously discharged through the 1-(4-chlorophenyl)-3-pyrazolol product outlet 18. The content of 1-(4-chlorophenyl)-3-pyrazolol detected by HPLC is 95.6%, and the product yield is 92%.

[0044] (6) The liquid phase outlet of the continuous filter 9 is connected to the inlet of the storage tank 10, and the mother liquor after filtration and separation in step (4) continuously enters the storage tank 10.

[0045] (7) After the mother liquor in the storage tank 10 reaches the volume upper limit, discharging operation is carried out. The mother liquor enters the ion resin exchanger 12 and Fe in the mother liquor is adsorbed by the ion resin. 3+ . The discharging speed of the storage tank 10 is greater than the feeding speed. The mother liquor in the storage tank 10 gradually decreases and stops discharging after reaching the volume lower limit. Flushing liquid is introduced through the backwashing port 15 at the side end of the ion resin exchanger 12, so that Fe 3+ is desorbed from the ion resin and returns to the first raw material premixing tank 1 with the flushing liquid from the flushing liquid outlet 17. The recycling of Fe 3+ is realized through the backwashing operation. The mother liquor after adsorption is discharged from the wastewater discharge port 16.

[0046] While the backwashing operation is in progress, the mother liquor after filtration and separation in step (4) continuously enters the storage tank 10. When the mother liquor volume in the storage tank 10 reaches the upper limit again, step (7) is repeated to realize the continuous treatment of the separated mother liquor.

[0047] Example 3: A continuous production method of 1-(4-chlorophenyl)-3-pyrazolol, which is applied to the continuous production system of 1-(4-chlorophenyl)-3-pyrazolol described in Example 1.

[0048] The difference between this example and Example 2 is that: in step (1), cuprous chloride is used to replace ferric trichloride as the transition metal ion catalyst, and the added mass of cuprous chloride is 23.76 g; in step (2), the total residence time of the premixed raw materials in the reaction unit is 1.5 min, and the reaction temperature is controlled at 63 °C by using the heat exchange jacket of the static mixing tube continuous flow reactor 13.

[0049] In this example, the content of 1-(4-chlorophenyl)-3-pyrazolol detected by HPLC is 95.1%, and the product yield is 97%.

[0050] Example 4: A continuous production method of 1-(4-chlorophenyl)-3-pyrazolol, which is applied to the continuous production system of 1-(4-chlorophenyl)-3-pyrazolol described in Example 1.

[0051] The differences between this example and Example 2 are as follows: In step (1), potassium ferricyanide is used as the transition metal ion catalyst instead of ferric chloride, and the added mass of potassium ferricyanide is 13.17 g; in step (1), potassium hydroxide is used as the inorganic base instead of sodium hydroxide, and the added mass of potassium hydroxide is 1178.31 g; in step (2), the total residence time of the premixed raw materials in the reaction unit is 0.9 min, and the heat exchange jacket of the static mixing tubular continuous flow reactor 13 is used to control the reaction temperature at 80 °C; in step (3), hydrochloric acid is introduced to adjust the pH to 3.5, and the stirring time is 15 min.

[0052] In this example, the content of 1-(4-chlorophenyl)-3-pyrazolol detected by HPLC is 97%, and the product yield is 95.4%.

[0053] Comparative Example 1: This comparative example uses a traditional batch hydrogen peroxide oxidation process to produce 1-(4-chlorophenyl)-3-pyrazolol. The molar ratio of 1-(4-chlorophenyl)pyrazolidin-3-one to hydrogen peroxide in the reaction kettle is 1.0:1.2 - 1.8, the temperature in the kettle is controlled at 75 °C - 90 °C, the dropping time of hydrogen peroxide is 2 - 3 h, and it needs to be kept warm for 0.5 h after the dropping is completed; after the reaction is completed, the temperature is lowered to 35 °C - 40 °C, 30% hydrochloric acid is dropped, adjusted to PH = 5, stirred for 1 h and then centrifuged, filtered and dried. The maximum content of 1-(4-chlorophenyl)-3-pyrazolol in the obtained product detected by HPLC is 90%, and the product yield is 75% - 82%.

[0054] Based on the experimental results of Examples 2 - 4 and Comparative Example 1, it can be seen that compared with Comparative Example 1, the continuous production method of 1-(4-chlorophenyl)-3-pyrazolol provided by Examples 2 - 4 realizes the production of 1-(4-chlorophenyl)-3-pyrazolol with high yield and high purity.

[0055] The present invention uses a production method of catalytic air oxidation of 1-(4-chlorophenyl)pyrazolidin-3-one with transition metal ions (Fe 3+ and Cu + ) to replace the traditional hydrogen peroxide oxidation process, significantly reducing production costs and process risks, reducing the generation and emission of wastewater, and realizing green and safe production.

[0056] The present invention uses a static mixing tubular continuous flow reactor 13 to replace the traditional batch kettle reaction. By setting static mixing elements with strong mixing effect and low resistance in the static mixing tubular continuous flow reactor 13, the gas-liquid two-phase mass transfer effect in the pipe is effectively strengthened, the residence time in the reactor is accurately controlled, the reaction efficiency and process controllability are improved, the occurrence of over-oxidation side reactions is avoided, and the production of 1-(4-chlorophenyl)-3-pyrazolol with high yield and high purity is realized.

[0057] The present invention realizes the recovery and reuse of the liquid-phase transition metal ion catalyst through the ion resin exchanger 12, reduces the salt content in the wastewater and the wastewater treatment pressure, and effectively reduces the production cost.

[0058] The present invention relies on the static mixing tubular continuous flow reactor 13, the continuous filter 9 and the continuous dryer 11 to realize the continuous production of the whole process of synthesis, filtration and drying of 1-(4-chlorophenyl)-3-pyrazolol, greatly improving the production efficiency, effectively reducing the floor area of the equipment, reducing the operation cost and operation risk, and realizing the industrial upgrading of the green and safe preparation of 1-(4-chlorophenyl)-3-pyrazolol.

[0059] Certainly, the above description is not a limitation of the present invention, and the present invention is not limited to the above examples. Changes, modifications, additions or substitutions made by those skilled in the art within the substantial scope of the present invention should also fall within the protection scope of the present invention.

Claims

1. A continuous production system for 1-(4-chlorophenyl)-3-pyrazolol, characterized in that, It includes a raw material premixing tank, a transfer pump, an air source, an ejector, a reaction unit, a pH adjustment tank, a continuous filter, a storage tank, a continuous dryer, and an ion resin exchanger. The reaction unit includes multiple static mixing tube-type continuous flow reactors connected in series. The ion resin exchanger includes an exchanger inlet at the top, a backwash port at the lower part, a waste water discharge port at the bottom, and a flushing liquid outlet at the upper part; The outlet of the raw material premixing tank is connected to the inlet of the transfer pump. The outlet of the transfer pump is connected to the inlet of the continuous phase pipeline of the ejector. The outlet of the air source is connected to the inlet of the discrete phase pipeline of the ejector. The outlet of the ejector is connected to the inlet of the reaction unit. The outlet of the reaction unit is connected to the inlet of the pH adjustment tank. The outlet of the pH adjustment tank is connected to the inlet of the continuous filter. The liquid phase outlet of the continuous filter is connected to the inlet of the storage tank. The solid phase outlet of the continuous filter is connected to the inlet of the continuous dryer. The outlet of the storage tank is connected to the exchanger inlet of the ion resin exchanger. The flushing liquid outlet of the ion resin exchanger is connected to the inlet of the raw material premixing tank; The raw material premixing tank is used for stirring and mixing the raw materials into a uniform premixed raw material. The transfer pump is used for transporting the premixed raw material through the continuous phase pipeline of the ejector to the static mixing tube-type continuous flow reactor of the reaction unit. The air source is used for providing the air required in the reaction process. The ejector is used for ejecting air into the reaction pipeline for co-current mixing with the premixed raw material. The static mixing tube-type continuous flow reactor is used for carrying out the oxidation reaction process of catalytically oxidizing 1-(4-chlorophenyl)pyrazolidin-3-one by oxygen in the air to synthesize 1-(4-chlorophenyl)-3-pyrazolol; The pH adjustment tank is used for precipitating the oxidized and synthesized liquid phase 1-(4-chlorophenyl)-3-pyrazolol in the form of a solid phase precipitate through pH adjustment to form a suspension; The continuous filter is used for continuous solid-liquid separation of the suspension. The storage tank is used for temporarily storing the mother liquor after filtration. The continuous dryer is used for continuously drying the solid phase 1-(4-chlorophenyl)-3-pyrazolol; The ion resin exchanger is used for recovering the transition metal ion catalyst. At the same time, the ion resin exchanger is used for returning the recovered liquid phase catalyst after backwashing to the raw material premixing tank.

2. The continuous production system of 1-(4-chlorophenyl)-3-pyrazolol according to claim 1, wherein There are multiple raw material premixing tanks, and the multiple raw material premixing tanks are arranged in parallel. During the raw material premixing process, continuous output of the premixed raw material is achieved through the switching cooperation between the raw material premixing tanks.

3. The continuous production system of 1-(4-chlorophenyl)-3-pyrazolol according to claim 2, wherein, A heat exchange jacket or coil is provided on the outer side wall of the raw material premixing tank.

4. The continuous production system of 1-(4-chlorophenyl)-3-pyrazolol according to claim 3, characterized in that, Static mixing elements are provided inside the static mixing tube-type continuous flow reactor, and a heat exchange jacket is provided outside the static mixing tube-type continuous flow reactor.

5. The continuous production system of 1-(4-chlorophenyl)-3-pyrazolol according to claim 4, characterized in that, There are multiple pH adjustment tanks, and the multiple pH adjustment tanks are arranged in parallel. During the pH adjustment process, continuous output of the suspension is achieved through the switching cooperation between the pH adjustment tanks; A heat exchange jacket or coil is provided on the outer side wall of the pH adjustment tank.

6. A continuous production method of 1-(4-chlorophenyl)-3-pyrazolol, characterized in that, Applied to the continuous production system of 1-(4-chlorophenyl)-3-pyrazolol according to any one of claims 1-5, it includes the following steps: S1. Put 1-(4-chlorophenyl)pyrazolidin-3-one, inorganic base, transition metal ion catalyst and water into the raw material premixing tank, stir and mix them, and control the temperature at 20-50°C to form a premixed raw material; Among them, the molar ratio of 1-(4-chlorophenyl)pyrazolidin-3-one to the inorganic base is 1:1.1-1.8, the molar ratio of 1-(4-chlorophenyl)pyrazolidin-3-one to the transition metal ion catalyst is 1:0.001-0.02, and the mass fraction of 1-(4-chlorophenyl)pyrazolidin-3-one is 10%-40%; S2. Use a transfer pump to transport the premixed raw material through the continuous phase pipeline of the ejector to the static mixing tubular continuous flow reactor in the reaction unit, and use the ejector to eject the air from the air source through the discrete phase pipeline into the static mixing tubular continuous flow reactor in the reaction unit; The 1-(4-chlorophenyl)pyrazolidin-3-one in the premixed raw material and the oxygen in the air carry out an oxidation reaction in the static mixing tubular continuous flow reactor to obtain liquid-phase 1-(4-chlorophenyl)-3-pyrazolol; The molar ratio of 1-(4-chlorophenyl)pyrazolidin-3-one to the oxygen in the air is 1:0.55-0.85, the reaction temperature is 40-90°C, the reaction pressure is 0.1-1.6 MPa, and the total residence time of the premixed raw material in the reaction unit is 0.6-10 min; S3. The liquid-phase 1-(4-chlorophenyl)-3-pyrazolol generated by the reaction enters the pH adjustment tank, and hydrochloric acid is introduced into the pH adjustment tank to adjust the pH to 3-6. Control the temperature in the pH adjustment tank at 30-50°C, and 1-(4-chlorophenyl)-3-pyrazolol precipitates in the form of a solid phase. The stirring time is 5-30 min; then cool down to 20-30°C to form a suspension; S4. Pass the suspension through a continuous filter for continuous solid-liquid separation, and separate it into solid-phase 1-(4-chlorophenyl)-3-pyrazolol and mother liquor; S5. The separated solid-phase 1-(4-chlorophenyl)-3-pyrazolol enters a continuous dryer, and the drying temperature is 60-95°C. After drying, the 1-(4-chlorophenyl)-3-pyrazolol product is obtained; S6. The separated mother liquor continuously enters the storage tank. When the mother liquor in the storage tank reaches the volume upper limit of the storage tank, an outfeed operation is carried out. The mother liquor enters the ion resin exchanger, and the transition metal ion catalyst in the mother liquor is adsorbed by the ion resin in the ion resin exchanger. The mother liquor after adsorption is continuously discharged in the form of wastewater; The outfeed speed of the storage tank is greater than the feed speed of the storage tank. The mother liquor in the storage tank gradually decreases and stops outfeeding after reaching the volume lower limit. Flushing liquid is introduced through the backwashing port of the ion resin exchanger, so that the transition metal ion catalyst is desorbed from the ion resin and returns to the raw material premixing tank with the flushing liquid.

7. The continuous production method of 1-(4-chlorophenyl)-3-pyrazolol according to claim 6, characterized in that, In step S1, there are two raw material premixing tanks, namely the first raw material premixing tank and the second raw material premixing tank. While the first raw material premixing tank outputs the premixed raw materials, the second raw material premixing tank performs the premixing operation of the raw materials; after the output of the premixed raw materials in the first raw material premixing tank is completed, the premixing operation of the raw materials is carried out again, and at the same time, the second raw material premixing tank is started to output the premixed raw materials; the continuous transportation process of the premixed raw materials is realized through the switching cooperation of the first raw material premixing tank and the second raw material premixing tank.

8. The continuous production method of 1-(4-chlorophenyl)-3-pyrazolol according to claim 7, characterized in that, In step S3, there are two pH adjustment tanks, namely the first pH adjustment tank and the second pH adjustment tank. When the first pH adjustment tank performs the pH adjustment to precipitate solid precipitates and discharge the suspension, the liquid phase of 1-(4-chlorophenyl)-3-pyrazolol is transported into the second pH adjustment tank. After the suspension in the first pH adjustment tank is discharged completely, the liquid phase of 1-(4-chlorophenyl)-3-pyrazolol is input into the first pH adjustment tank again, and at the same time, the liquid phase of 1-(4-chlorophenyl)-3-pyrazolol stops entering the second pH adjustment tank, and the pH adjustment is carried out in the second pH adjustment tank to precipitate solid precipitates and discharge the suspension; the continuous post-treatment process of the suspension is realized through the switching cooperation of the first pH adjustment tank and the second pH adjustment tank.

9. The continuous production method of 1-(4-chlorophenyl)-3-pyrazolol according to claim 8, characterized in that, In step S6, while the backwashing operation is carried out, the separated mother liquor continuously enters the temporary storage tank. When the volume upper limit in the temporary storage tank is reached again, step S6 is repeated to realize the continuous treatment of the separated mother liquor.

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