A synthesis reaction device for a piperazine pyrazine pharmaceutical intermediate

Abstract

The application discloses a kind of synthesis reaction devices of piperazine pyrazine medical intermediates, it is related to the technical field of preparation of pharmaceutical intermediates, including workbench and the reaction tank of installation in one side of workbench, temperature control jacket is installed outside the reaction tank, excess ammonia gas after ammonia gas reaction can be recycled by gas phase circulation mechanism, and recycling ammonia gas is used in solid-phase feeding mechanism, liquid-phase feeding mechanism, it is favorable to reduce the consumption cost of gas phase raw material;The solid-phase feeding mechanism of the application utilizes recycled ammonia gas to carry out multi-section processing to solid-phase raw material, realizes the continuous uniform feeding of solid-phase material, and solid-phase material is more fully dispersed, recycling ammonia gas is used throughout, no exogenous gas is introduced, and closed circuit cycle is maintained;The liquid-phase feeding mechanism of the application utilizes recycled ammonia gas to float, crystallize liquid-phase raw material, and discards traditional filter core type impurity removal structure, without filter core consumables, without filter core blockage, attenuation failure.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical intermediate preparation technology, specifically to a synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates. Background Technology

[0002] The synthetic reaction apparatus for pharmaceutical intermediates is the core production carrier in the synthesis of piperazine / pyrazine pharmaceutical intermediates. It is mainly used in high-temperature and high-pressure reaction processes such as amination cyclization and ammonolysis condensation. In the production of key pharmaceutical intermediates such as anhydrous piperazine and alkylpyrazine, this equipment needs to simultaneously complete functions such as gas-liquid-solid three-phase material mixing, precise temperature control heating, high-pressure closed reaction, and real-time monitoring of the reaction process. It provides a stable reaction environment for raw material conversion and product generation, which directly determines the conversion rate, selectivity and purity of intermediates.

[0003] Currently, in traditional processes, after the ammonia gas introduced into the reaction system participates in the amination and cyclization reaction, the unreacted excess ammonia gas and the free ammonia dissolved in the liquid phase material are mostly directly discharged with the tail gas, making it difficult to achieve recycling. On the one hand, as the core gaseous raw material, the single-pass conversion rate of ammonia gas is limited by reaction equilibrium and mass transfer efficiency. If it is not efficiently recovered, a large amount of unreacted ammonia gas is directly discharged into the waste gas treatment system, which not only results in low utilization rate of gaseous raw materials and high unit consumption, but also significantly increases raw material costs and production economic pressure. On the other hand, the direct discharge of ammonia gas without returning it to the reaction system to participate in the secondary reaction greatly increases the amount of ammonia gas required to replenish the system, further aggravating raw material waste and restricting the improvement of overall reaction efficiency and product yield.

[0004] Meanwhile, during continuous feeding, solid catalysts are highly susceptible to stable bridging and arched blockages in silos, discharge ports, and feed pipelines due to their small particle size, high surface energy, strong hygroscopicity, and the humid environment containing ammonia. This leads to interruptions in material feeding and drastic fluctuations in feed flow. Furthermore, catalyst particles are prone to agglomeration, clumping, pulverization, and adhesion under long-term static conditions and airflow disturbances, forming unevenly sized aggregates. This not only disrupts the original particle size distribution of the catalyst but also significantly reduces its effective specific surface area and catalytic activity. Moreover, these materials further exacerbate the uneven mixing when mixed into the reaction system. All of these problems together result in unstable solid catalyst feeding, poor metering accuracy, and localized high or low concentrations. This directly disrupts the equilibrium of the gas, liquid, and solid phases in the reaction system, significantly reducing the system's mixing and mass transfer efficiency, causing localized overheating, increased side reactions, and decreased product selectivity. Ultimately, this severely affects the synthesis yield, product purity, and batch stability of piperazine / pyrazine intermediates.

[0005] Furthermore, in the synthesis and post-processing of piperazine / pyrazine pharmaceutical intermediates, traditional processes often employ conventional cartridge filtration to purify the reaction solution, removing entrained solid catalyst particles, by-product salts, and mechanical impurities. However, this type of filtration has significant drawbacks in actual production. During long-term operation, the filter cartridges are easily clogged by fine particles, with blockages occurring primarily inside the cartridge. Conventional backwashing and cleaning are insufficient to completely remove trapped impurities, resulting in limited cleaning effectiveness. As the usage time increases, the filter cartridge pressure differential rises rapidly, and the throughput continuously declines, necessitating frequent shutdowns for disassembly and replacement. This not only significantly increases the frequency of shutdowns and maintenance workload, severely disrupting production continuity but also makes it difficult for the equipment to achieve long-term stable operation. Moreover, since the filter cartridge is a disposable consumable component, frequent replacement directly leads to high consumable costs. Furthermore, discarded filter cartridges carry materials and residual ammonia, increasing the amount of hazardous waste to be treated and the environmental disposal pressure. Summary of the Invention

[0006] To address the above problems, this invention provides a synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates, thus solving the aforementioned issues.

[0007] To achieve the above objectives, the present invention provides the following technical solution: a synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates, comprising a workbench and a reaction vessel installed on one side of the workbench, wherein a temperature control jacket is installed on the outside of the reaction vessel, a stirring component is installed on the reaction vessel, a solid phase feeding mechanism is connected to the reaction vessel, a liquid phase feeding mechanism is connected to the reaction vessel, a gas phase circulation mechanism is connected to the reaction vessel, and a detection mechanism is provided on one side of the reaction vessel; The solid-phase feeding mechanism includes a feeding pipe, and a gas supply diversion pipe is provided outside the feeding pipe. The gas phase circulation mechanism is connected to the gas supply diversion pipe to supply gas. The feeding pipe is provided with an anti-bridging section, a clump breaking section, a flow section, a pulse section, and a check-diffusion section. The liquid-phase feeding mechanism includes a liquid-phase gas separation component, a gas-induced crystallization component, and a liquid-phase feeding component. The gas phase circulation mechanism is connected to the liquid-phase gas separation component, the gas-induced crystallization component, and the liquid-phase feeding component to supply gas.

[0008] Preferably, the anti-bridging section is provided with a truncated cone ring, the top of which is connected to a first air distribution ring, and the bottom of the first air distribution ring is connected to several conical nozzles. The bridging section is provided with a receiving ring, which has a sliding groove. A suspended impeller is provided in the receiving ring, and the outer side of the suspended impeller is slidably connected to the sliding groove. An oblique swirling air ring is provided above the suspended impeller, and the bottom of the oblique swirling air ring is connected to several left-handed nozzles. An arc plate is connected to the outer side of the suspended impeller. Several oblique air nozzles are connected to the receiving ring. The first air distribution ring, the oblique swirling air ring, and the oblique air nozzles are all connected to the air supply distribution pipe.

[0009] Preferably, the flow section is provided with a contraction element, and a second gas distribution ring is provided above the contraction element. Several high-pressure flow nozzles are connected to the bottom of the second gas distribution ring. The high-pressure flow nozzles mix with the solid material to form a high-speed material jet. The pulse section is provided with a left-handed gas ring and a right-handed gas ring. The left-handed gas ring and the right-handed gas ring are circumferentially distributed. Several electromagnetic pulse nozzles are connected to the bottom of the left-handed gas ring and the right-handed gas ring. The electromagnetic pulse nozzles work on the material falling path to form a strong shear turbulence layer. The second gas distribution ring, the left-handed gas ring, and the right-handed gas ring are all connected to the gas supply diversion pipe.

[0010] Preferably, the check flow diffusion section is provided with a guide ring, and a gas distribution ring three is installed on the guide ring. Several check flow nozzles are connected to the bottom of the gas distribution ring three. A gas distribution ring four is provided below the guide ring. Several diffusion nozzles are connected to the inner side of the gas distribution ring four. The several diffusion nozzles work in sequence. Both the gas distribution ring three and the gas distribution ring four are connected to the gas supply diversion pipe.

[0011] Preferably, the gas-phase circulation mechanism includes a microporous aerator installed at the bottom of the reaction tank. An air inlet pipe and a circulation pipe are connected to the bottom of the microporous aerator. The air inlet pipe is connected to an external ammonia supply device. One end of the circulation pipe is connected to the top of the reaction tank and extends through the top of the reaction tank. A collection head is provided at the top of the reaction tank. One end of the circulation pipe is connected to the collection head. An ammonia purification box is connected to the workbench and is connected to the circulation pipe. A gas supply pipe is connected to one side of the ammonia purification box, providing recovered ammonia to the solid-phase feeding mechanism and the liquid-phase feeding mechanism.

[0012] Preferably, the liquid-phase gas separation component includes a liquid phase tube, a spiral baffle connected in the liquid phase tube, a bubble generator connected to the bottom of the liquid phase tube, a liquid inlet pipe connected to the middle of the liquid phase tube, a liquid delivery pipe connected to the lower part of the liquid phase tube, a foam overflow pipe connected to the upper part of the liquid phase tube, and a gas supply ring connected to the upper part of the liquid phase tube. Several purge nozzles are connected to one side of the gas supply ring. The bubble generator and the gas supply ring are both connected to the gas phase circulation mechanism.

[0013] Preferably, the gas-induced crystallization component includes a second liquid phase tube, the upper part of which is connected to a first liquid delivery tube, the upper part of which is connected to the second liquid delivery tube, a flow baffle plate connected in the second liquid phase tube, a cooling ring plate connected inside the second liquid phase tube, a high-pressure ammonia injector connected to the top of the second liquid phase tube, the high-pressure ammonia injector being connected to a gas phase circulation mechanism, and a crystallization temporary storage shell connected to the bottom of the second liquid phase tube.

[0014] Preferably, the liquid phase feeding component includes a liquid phase tube three, the upper part of which is connected to a liquid delivery tube two, a microporous filter membrane connected in the liquid phase tube three, a re-filter tube connected in the middle of the liquid phase tube three, the other end of which is connected to the liquid inlet pipe of the liquid phase gas separation component, a liquid phase feeding tube connected in the lower part of the liquid phase tube three, the other end of which is connected to the top of the reaction tank, and an ammonia backflush device connected to the bottom of the liquid phase tube three, which is connected to the gas phase circulation mechanism.

[0015] Preferably, the detection mechanism includes a sampling head, a chromatograph, and a waste liquid tank. The sampling head is connected to the reaction vessel, and one end of the sampling head is connected to a sampling tube. A metering pump is installed on the sampling tube, and one end of the sampling tube is connected to a detection delivery tube and a waste liquid delivery tube. The detection delivery tube is connected to the chromatograph, and the waste liquid delivery tube is connected to the waste liquid tank.

[0016] Preferably, the top of the reaction vessel is connected to several vessel interfaces, the bottom of the reaction vessel is connected to a discharge pipe, and one side of the temperature control jacket is connected to several jacket interfaces.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This application can recover excess ammonia after the ammonia reaction through a gas phase circulation mechanism, and use the recovered ammonia in the solid phase feeding mechanism and liquid phase feeding mechanism. This achieves the effect of recovering excess ammonia after the reaction and reusing this ammonia, which solves the problem of low ammonia utilization rate and serious waste of gas phase raw materials in traditional processes after ammonia participates in the reaction and is conducive to reducing the consumption cost of gas phase raw materials. 2. The solid-phase feeding mechanism of this application utilizes recovered ammonia to process solid raw materials in multiple stages, achieving continuous and uniform feeding of solid materials and more thorough dispersion of solid materials. The entire process utilizes recovered ammonia, eliminating the introduction of external gases and maintaining a closed-loop system circulation. This solves the problems of bridging and blockage, particle agglomeration and clumping, uneven feeding, and material adhesion to the wall surface that easily occur during the feeding process of solid catalyst materials, affecting the feeding efficiency of solid materials and the efficiency of subsequent mixing and reaction. It is beneficial to improve the feeding efficiency and feeding quality of solid materials in mixing and heating reaction equipment. 3. The liquid phase feeding mechanism of this application utilizes recovered ammonia gas to perform flotation and crystallization of liquid phase raw materials, eliminating the need for traditional filter cartridge-type impurity removal structures. It eliminates the need for filter cartridge consumables, and avoids filter cartridge clogging and attenuation failure. This solves the problems of traditional processes that use filter cartridges for liquid phase impurity removal, such as easy filter cartridge clogging, frequent shutdowns for replacement, difficulty in cleaning deep-seated impurities, high consumable costs, and poor production continuity. It is beneficial to improve the practical performance of mixing and heating reaction equipment and reduce operating costs. 4. This application allows for the automatic sampling and testing of materials in a mixed reaction by a testing agency. It can even automatically detect the reaction status of materials by using multiple reaction vessels in conjunction with a single chromatograph. This solves the problem that traditional mixed heating reaction equipment still requires manual sampling of reaction materials at regular intervals and transfer to testing equipment for testing. This is beneficial to improving the automation level of mixed heating reaction equipment and reducing the labor intensity of operators. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the overall first-view structure of the present invention; Figure 2 This is a schematic diagram of the overall second-view structure of the present invention; Figure 3 This is a schematic diagram of the liquid phase feeding mechanism of the present invention; Figure 4 This is a schematic diagram of the liquid phase tube structure of the present invention; Figure 5 This is a schematic diagram of the liquid phase tube structure of the present invention; Figure 6 This is a schematic diagram of the three-structure liquid phase tube of the present invention; Figure 7 This is a schematic diagram of the liquid phase feed direction of the present invention; Figure 8 This is a schematic diagram of the solid-phase feeding mechanism of the present invention; Figure 9 This is a schematic diagram of the detection mechanism structure of the present invention; Figure 10 This is a schematic cross-sectional view of the reaction vessel of the present invention; Figure 11 This is a schematic diagram of the gas phase circulation mechanism of the present invention.

[0019] Figure labeling: 1. Workbench; 2. Reaction vessel; 201. Temperature control jacket; 202. Vessel interface; 203. Discharge pipe; 204. Jacket interface; 3. Stirring component; 4. Solid phase feeding mechanism; 5. Feed pipe; 6. Anti-bridging section; 7. Agglomeration section; 8. Flow section; 9. Pulse section; 10. Check valve diffusion section; 11. Truncated cone ring; 12. Gas distribution ring one; 13. Conical nozzle; 14. Reception ring; 15. Suspension. 16. Floating impeller; 17. Oblique swirling air ring; 18. Left-handed swirling nozzle; 19. Arc plate; 20. Oblique air nozzle; 21. Contractor; 22. Gas distribution ring II; 23. High-pressure flow nozzle; 24. Left-handed swirling air ring; 25. Right-handed swirling air ring; 26. Electromagnetic pulse nozzle; 27. Guide ring; 28. Gas distribution ring III; 29. ​​Check nozzle; 30. Gas distribution ring IV; 31. Diffusion nozzle; 32. Liquid phase feeding mechanism; 33. Liquid phase gas separation component; 34. Gas-induced crystallization component; 35. Liquid phase feeding component; 36. Liquid phase pipe one; 37. Spiral baffle; 38. Bubble generator; 39. Liquid inlet pipe; 40. Liquid delivery pipe one; 41. Foam overflow pipe; 42. Gas supply ring; 43. Purge nozzle; 44. Liquid phase pipe two; 45. Baffle plate; 46. Cooling ring plate; 47. High-pressure ammonia injector; 48. Crystallization temporary storage shell; 49. Liquid delivery pipe two; 50. Liquid phase pipe three; 61. Micro 51. Porous filter membrane; 52. Re-filter tube; 53. Ammonia backflush device; 54. Liquid phase feed tube; 55. Gas phase circulation mechanism; 56. Microporous aerator; 57. Air inlet pipe; 58. Circulation pipe; 59. Collection head; 60. Ammonia purification box; 61. Air supply pipe; 62. Detection mechanism; 63. Sampling head; 64. Sampling tube; 65. Metering pump; 66. Detection and delivery pipe; 67. Waste liquid delivery pipe; 68. Chromatograph; 69. Waste liquid tank. Detailed Implementation

[0020] The embodiments of the present invention will be described in further detail below with reference to the accompanying drawings and examples. The following examples are for illustrative purposes only and should not be construed as limiting the scope of the invention.

[0021] Please see Figure 1 , Figure 2A synthetic reaction apparatus for piperazine / pyrazine pharmaceutical intermediates includes a workbench 1 and a reaction vessel 2 installed on one side of the workbench 1. A temperature-controlled jacket 201 is installed on the outside of the reaction vessel 2. The reaction vessel 2 is the core reaction chamber for the preparation of pharmaceutical intermediates and is the main site for the synthetic reaction of piperazine / pyrazine pharmaceutical intermediates. Liquid materials, ammonia, and a solid catalyst undergo mixing, contact, heating, and amination / cyclization reactions inside the reaction vessel 2, ultimately generating the target pharmaceutical intermediate. The reaction vessel 2 adopts a closed, pressure-bearing structure, capable of handling gas under high temperature and high pressure. The liquid-solid three-phase reaction provides a stable and safe reaction space, while ensuring that the materials are fully stirred and mixed inside, improving the reaction conversion rate and product selectivity. The temperature control jacket 201 is installed on the outer wall of the reaction tank 2 and is used to accurately heat, keep the temperature constant or cool the materials inside the reaction tank. The temperature control jacket 201 is a closed jacket structure and is equipped with an electric heater (such as a heating coil or electromagnetic induction heating coil). The current flows through the resistance heating element to directly convert electrical energy into heat energy, and the heat energy is quickly transferred to the materials inside the tank to achieve direct and efficient heating. Specifically, a high-precision temperature sensor (such as a PT100 platinum resistance thermometer) is installed inside reaction vessel 2 to collect the actual temperature of the materials in real time and transmit the temperature signal to the electrical control system. The control system compares the real-time temperature with the set process temperature and automatically adjusts the output power through a PID algorithm: when the material temperature is lower than the set value, the controller increases the heating power for rapid reheating; when the temperature approaches the set value, it automatically reduces the heating power to avoid overheating; when the temperature reaches the set value, the system enters a low-power constant temperature maintenance state to keep the temperature stable, thereby achieving precise and controllable temperature, uniform heating, and zero emissions throughout the entire reaction process. Local overheating ensures a stable reaction, improves the yield and purity of piperazine / pyrazine intermediates, and avoids side reactions. A stirring component 3 is installed on the reaction vessel 2. The reaction vessel 2 uses the stirring component 3 to stir and mix the three-phase materials. The stirring component 3 is a conventional motor-driven stirring structure. Those skilled in the art can and should understand its specific function and structure, so it will not be described in detail here. A solid phase feeding mechanism 4 is connected to the reaction vessel 2. A liquid phase feeding mechanism 31 is connected to the reaction vessel 2. A gas phase circulation mechanism 54 is connected to the reaction vessel 2. A detection mechanism 61 is set on one side of the reaction vessel 2. Please see Figure 8The solid-phase feeding mechanism 4 includes a feed pipe 5, and a gas supply diversion pipe is provided outside the feed pipe 5. The gas phase circulation mechanism 54 is connected to the gas supply diversion pipe for gas supply. The feed pipe 5 is provided with an anti-bridging section 6, a clump breaking section 7, a flow section 8, a pulse section 9, and a check-diffusion section 10. The liquid-phase feeding mechanism 31 includes a liquid-phase gas separation component 32, a gas-induced crystallization component 33, and a liquid-phase feeding component 34. The gas phase circulation mechanism 54 is connected to the liquid-phase gas separation component 32, the gas-induced crystallization component 33, and the liquid-phase feeding component 34 for gas supply. The gas phase circulation mechanism 54 recovers the excess ammonia gas after the reaction in the reaction tank 2. After recovery, the ammonia gas can be reinjected into the solid-liquid mixture through the microporous aerator 55 for further reaction. Alternatively, the recovered ammonia gas can be supplied to the solid phase feeding mechanism 4 and the liquid phase feeding mechanism 31. The circulating ammonia gas can be used to pre-treat the solid phase material without the need for a mechanical transmission structure. It can also be used to treat the liquid phase material without the need for a traditional filter structure.

[0022] The anti-bridging section 6 is equipped with a truncated cone ring 11. The top of the truncated cone ring 11 is connected to an air distribution ring 12, and the bottom of the air distribution ring 12 is connected to several conical nozzles 13. The anti-bridging section 6 is located at the uppermost end of the feed pipe 5. The truncated cone ring 11 is an inverted cone-shaped ring that is wider at the top and narrower at the bottom. Its outer ring edge is fixed to the inner wall of the feed pipe 5. The cone angle of the truncated cone ring 11 is a convergent angle with the axis of the feed pipe 5, which is used to reduce the flow cross-sectional area of ​​the falling material and form the installation reference of the annular air curtain. The conical nozzles 13 serve as the execution unit for air curtain spraying. They have an oblique cone structure and are evenly installed on the bottom end face of the air distribution ring 12. Each conical nozzle 13 is supplied with air through the air distribution ring 12. All the working air from the conical nozzles 13 forms an annular air curtain along the inner wall of the truncated conical ring 11. This air curtain flows tightly against the inner wall, effectively creating a dynamic gas isolation layer between the material and the wall. When solid catalyst particles fall along the inner wall of the truncated conical ring 11, the particles first contact the air curtain, rather than directly contacting the metal wall. The airflow lifts and guides the particles, keeping them in a suspended state and preventing direct contact and friction between the particles and the wall. Furthermore, the high-speed airflow continuously sweeps the inner wall, promptly removing adhesion caused by humidity and static electricity, disrupting the conditions for particle agglomeration and wall adhesion, thus fundamentally preventing solid material adhesion and bridging. To address issues such as scaling and material blockage, and ensure smooth, uniform, and continuous material feeding, the breaking section 7 is equipped with a receiving ring 14. A sliding groove is formed within the receiving ring 14, and a suspended impeller 15 is installed within it. The outer side of the suspended impeller 15 is slidably connected to the sliding groove. The suspended impeller 15 is integrally molded from 316L stainless steel with a mirror-polished surface. 316L material possesses excellent corrosion resistance, high-temperature resistance, and structural strength, capable of withstanding long-term corrosion from media such as ammonia and amines. This prevents rusting, leaching of impurities, or structural deformation under high-temperature and high-pressure reaction environments, ensuring equipment lifespan and material cleanliness. It meets the hygiene and safety requirements for pharmaceutical intermediate production. Furthermore, the surface of the suspended impeller 15 is... After mirror polishing, the surface roughness is extremely low, and the wall surface is smooth without dead corners. On the one hand, this significantly reduces the adhesion between solid catalyst particles and materials, preventing catalyst agglomeration, scaling, and wall adhesion on the impeller surface, ensuring smooth impeller rotation and uniform mixing. On the other hand, the smooth surface is less likely to retain materials and residual impurities. It should be noted that the upper and lower ends of the outer side of the suspended impeller 15 are equipped with ball bearings. These ball bearings move in the sliding groove, allowing the suspended impeller 15 to rotate in the feed pipe 5, thereby shearing and crushing the solid material. Simultaneously, the rotation of the suspended impeller 15 also draws the material continuously downwards for feeding. An oblique swirling air ring 16 is installed above the suspended impeller 15. The bottom of the oblique swirl ring 16 is connected to several left-handed nozzles 17. The outer side of the suspended impeller 15 is connected to an arc plate 18. The receiving ring 14 is connected to several oblique air nozzles 19. The oblique air nozzles 19 blow ammonia gas towards the outer arc plate 18 of the suspended impeller 15 to drive the suspended impeller 15 to rotate. At the same time, the oblique swirl ring 16 also sprays the purified circulating ammonia gas at high speed from the left-handed nozzles 17 to form a left-handed swirling flow field. The two work together to drive the suspended impeller 15 to rotate at high speed. There is no additional electric drive required, which is perfectly suitable for medical cleanroom scenarios. All of them use circulating ammonia gas and no additional gas source is needed. The gas distribution ring 12, the oblique swirl ring 16, and the oblique air nozzles 19 are all connected to the gas supply distribution pipe.

[0023] The flow section 8 is equipped with a converging element 20. Above the converging element 20 is a second gas distribution ring 21. Several high-pressure flow nozzles 22 are connected to the bottom of the second gas distribution ring 21. The high-pressure flow nozzles 22 mix with the solid material to form a high-speed material stream. The material crushed by the suspended impeller 15 enters the converging element 20 with the airflow. The converging element 20 is a Venturi channel, which forms a strong negative pressure zone at the throat, which can accelerate the material to form a high-speed material stream. Furthermore, the high-pressure ammonia gas sprayed from the high-pressure flow nozzles 22 mixes thoroughly with the material stream in the negative pressure zone, instantly accelerating the material stream. The material is dispersed into a fluidized gas-solid two-phase flow, completely dissolving the soft agglomerates and bridging structures between particles, achieving deep deagglomeration. Then, under the deceleration effect of the Venturi diffuser section of the contraction element 20, the fluidized material can be smoothly conveyed downwards without turbulence, back-mixing, or wall adhesion, while ensuring continuous and stable feeding without material stagnation within the feed pipe 5. The pulse section 9 is equipped with a left-handed swirling air ring 23 and a right-handed swirling air ring 24, which are circumferentially distributed. Several electromagnetic electrodes are connected to the bottom of both the left-handed and right-handed swirling air rings 23 and 24. Regarding the pulse nozzle 25, it should be noted that while the left-hand spiral air ring 23 and the right-hand spiral air ring 24 rotate in the same direction and descend in a spiral, the electromagnetic pulse nozzles 25 on the left-hand spiral air ring 23 and the right-hand spiral air ring 24 are tilted in opposite directions. Therefore, to distinguish these two air rings with the same rotation direction, they are specifically referred to as the left-hand spiral air ring 23 and the right-hand spiral air ring 24. The electromagnetic pulse nozzle 25 is tilted, specifically, it is generally tilted to the left on the left-hand spiral air ring 23 and generally tilted to the right on the right-hand spiral air ring 24. The electromagnetic pulse nozzle 25 operates along the material falling path. A strong shear turbulence layer is formed. After the fluidized and deagglomerated material enters the pulse section 9, the left-hand swirling air ring 23 and the right-hand swirling air ring 24 cooperate with the inclined electromagnetic pulse nozzle 25 to form a high-frequency oscillating axial shear flow field in the tube, rather than a radial countercurrent field. This not only avoids the material being blown back and blocking the tube, but also forms a high-intensity reciprocating shear. The material is repeatedly sheared, collided and dispersed in the high-frequency oscillating flow field. The remaining micron-sized soft agglomerates and microcrystalline agglomerates are completely broken into monodisperse uniform powders, achieving final agglomeration and ensuring that the material entering the reaction tank 2 has no agglomerated structure. Specifically, the electromagnetic pulse nozzles 25 of the left-hand rotating gas ring 23 and the right-hand rotating gas ring 24 in the circumferential direction will naturally form a staggered distribution of clockwise and counterclockwise, clockwise and counterclockwise, which will form a dense small-scale reverse shear turbulence layer inside the pipe. When the material falls, it is repeatedly kneaded and torn, and the micro-agglomerates are completely broken. The gas distribution ring 21, the left-hand rotating gas ring 23, and the right-hand rotating gas ring 24 are all connected to the gas supply diversion pipe.

[0024] The check-back diffusion section 10 is equipped with a guide ring 26, on which a gas distribution ring 27 is installed. Several check-back nozzles 28 are connected to the bottom of the gas distribution ring 27. Below the guide ring 26 is a gas distribution ring 29, on which several diffusion nozzles 30 are connected to the inner side. The diffusion nozzles 30 operate sequentially. Both the gas distribution rings 27 and 29 are connected to the gas supply distribution pipe. The treated homogeneous solid material reaches the guide ring 26. The gas distribution ring 27 supplies gas to the check-back nozzles 28, causing the check-back nozzles 28 to be positioned above the guide ring 26. The downward blowing of air prevents the hot and humid ammonia gas and solvent vapor in the reaction tank 2 from flowing back into the feed pipe 5. At the same time, several diffusion nozzles 30 work in sequence to moderately purge the solid material entering the reaction tank 2, so that the solid material can enter the reaction tank 2 in a dispersed manner for reaction. This effectively improves the problem of local accumulation and uneven distribution of solid material after feeding, fully exposes the catalytic active sites of solid material, improves reaction conversion rate and product selectivity, and reduces the phenomenon of local overheating and increased side reactions caused by material agglomeration, ensuring that the reaction process proceeds stably and efficiently. The solid-phase feeding mechanism 4 utilizes recovered ammonia to process solid raw materials in multiple stages, achieving continuous and uniform feeding of solid materials and more thorough dispersion of solid materials. The entire process utilizes recovered ammonia, eliminating the introduction of external gases and maintaining a closed-loop system circulation. This solves the problems that easily occur during the feeding process of solid catalyst materials, such as bridging and blockage, particle agglomeration and clumping, uneven feeding, and material adhesion to the wall surface, which affect the feeding efficiency of solid materials and the efficiency of subsequent mixing and reaction. It is beneficial to improve the feeding efficiency and feeding quality of solid materials in mixing and heating reaction equipment. It should be noted that the gas supply is provided by the gas phase circulation mechanism 54 in conjunction with the gas supply diversion pipe. The corresponding installation and arrangement are all conventional and well-known technologies, which are conventional means that can be understood and implemented by those skilled in the art based on common sense. Therefore, they will not be described in detail here.

[0025] Please see Figure 10 , Figure 11The gas-phase circulation mechanism 54 includes a microporous aerator 55, which is installed at the bottom of the reaction tank 2. The bottom of the microporous aerator 55 is connected to an inlet pipe 56 and a circulation pipe 57. The inlet pipe 56 is connected to an external ammonia supply device. The microporous aerator 55 has a porous dispersion aeration structure. Its core function is to break the externally introduced ammonia and circulating ammonia into a large number of tiny, uniform bubbles and evenly disperse them into the reaction system, enhancing gas-liquid mass transfer. One end of the circulation pipe 57 is connected to the top of the reaction tank 2 and extends through the top of the reaction tank 2. A collection head 58 is provided at the top of the reaction tank 2, and one end of the circulation pipe 57 is connected to the collection head 58. An ammonia purification box 59 is connected to the workbench 1. The ammonia purification box 59 is used to purify and remove impurities from the circulating ammonia recovered from the top of the reaction tank 2. Drying and pressure stabilization processes ensure that the purity of the circulating ammonia meets the reaction requirements, preventing the accumulation of impurities from affecting catalytic efficiency and product purity. Specifically, after the recovered ammonia is extracted from the upper gas phase space of reaction tank 2, it first enters the ammonia purification box 59. The box is equipped with a demisting and condensation unit, an adsorption and filtration unit, and a drying unit in sequence. First, the demisting and condensation unit separates the mist droplets, volatile solvents, and moisture entrained in the ammonia, removing liquid impurities in the gas phase and preventing moisture and organic matter from entering the circulation system. Then, the ammonia flows through the adsorption and filtration layer to remove trace amounts of solid dust, catalyst debris, and by-product volatile impurities, preventing impurities from accumulating in the system and causing catalyst poisoning or pipeline blockage. Finally, the drying module further removes residual moisture from the ammonia, improving the purity and dryness of the circulating ammonia. After undergoing multi-stage purification, the ammonia gas has significantly reduced impurity content and stable purity that meets reaction requirements. It is then reintroduced into reaction tank 2 to participate in the reaction or supplied to the solid-phase feed mechanism 4 and liquid-phase feed mechanism 31, thus achieving closed-loop circulation, efficient reuse, and continuous stability of ammonia gas. This improves raw material utilization and ensures long-term stable operation of the reaction system. The ammonia purification tank 59 is connected to the circulation pipe 57, and a gas supply pipe 60 is connected to one side of the ammonia purification tank 59. The gas supply pipe 60 provides the recovered ammonia gas to the solid-phase feed mechanism 4 and liquid-phase feed mechanism 31. In the synthesis reaction of piperazine / pyrazine pharmaceutical intermediates, ammonia gas, as a core gaseous reactant, typically needs to be introduced in excess to… To shift the chemical equilibrium towards the product and improve the conversion rate of raw materials and the yield of products, the conversion of ammonia and liquid raw materials cannot be completely completed in a single pass due to the limitations of reaction kinetics and phase equilibrium. Unreacted free ammonia always exists in the system. At the same time, the solubility of ammonia in the liquid phase is limited. Excess undissolved and residual ammonia will continuously desorb and escape from the liquid phase, accumulating in the gas phase space above the inside of reaction vessel 2, forming a high concentration of ammonia atmosphere. Therefore, even if the reaction continues, a large amount of unreacted ammonia will still accumulate in the upper part of reaction vessel 2. If it is not recycled, this part of ammonia can only be discharged or vented, which wastes raw materials and reduces the utilization rate of ammonia. The ammonia gas can be recovered to the circulation pipe 57 through the collection head 58 at the top of the reaction tank 2. Specifically, the recovered ammonia gas needs to be treated by the ammonia gas purification box 59 before it can be reused. On the one hand, it can be directly fed back to the microporous aerator 55 for reuse in the reaction. On the other hand, it can be transported to the gas supply pipe 60 to provide the recovered ammonia gas to the solid phase feeding mechanism 4 and the liquid phase feeding mechanism 31. This achieves the effect of recovering excess ammonia gas after the reaction and reusing this ammonia gas. It solves the problem of low ammonia gas utilization rate and serious waste of gas phase raw materials in traditional processes, which are caused by direct discharge or partial venting of ammonia gas after participating in the reaction. This helps to reduce the consumption cost of gas phase raw materials.

[0026] Please see Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 The liquid-phase gas separation component 32 includes a liquid phase tube 35, a spiral baffle 36 connected in the liquid phase tube 35, a bubble generator 37 connected to the bottom of the liquid phase tube 35, an inlet pipe 38 connected to the middle of the liquid phase tube 35, a delivery pipe 39 connected to the lower part of the liquid phase tube 35, a foam overflow pipe 40 connected to the upper part of the liquid phase tube 35, and an air supply ring 41 connected to the upper part of the liquid phase tube 35. Several purge nozzles 42 are connected to one side of the air supply ring 41. The bubble generator 37 and the air supply ring 41 are both connected to the gas phase circulation mechanism 54. The inlet pipe 38 tangentially introduces liquid phase material into the liquid phase tube 35. The liquid phase material flows within the tube... A rotating vortex is formed. At this time, the spiral baffle 36 guides and constrains the tangentially entering rotating liquid flow, so that the material continues to advance along the spiral path, avoids vortex attenuation, maintains a stable centrifugal rotation state, and strengthens the internal disturbance of the liquid phase. At the same time, when the bubble generator 37 is working, it will use the recycled ammonia to introduce a large number of uniform microbubbles into the liquid phase. During the rising process, these microbubbles will adsorb the suspended solid impurities, trace amounts of oil, catalyst fine powder, by-product flocculents and other hydrophobic or weakly surface-active particles in the liquid phase, and attach to the bubble surface. They will float to the liquid surface together with the bubbles and eventually gather at the top of the liquid phase to form a foam layer. At this time, the gas supply ring 41 supplies the ammonia gas recovered by the gas phase circulation mechanism 54 to the purge nozzle 42. The purge nozzle 42 can blow the foam layer accumulated at the top of the liquid phase toward the foam overflow pipe 40. These foam layers with impurities will flow into the waste liquid tank 68 through the foam overflow pipe 40. It is important to note that because the bubbles rise from the bottom up, they will first remove impurities from the lower liquid phase material. Therefore, the liquid delivery pipe 39 is located at the lower part of the liquid phase pipe 35. The cleaned liquid phase material will be transported to the liquid phase pipe 43 for further processing through the liquid delivery pipe 39 at the lower part of the liquid phase pipe 35. It should be further explained that the spiral baffle 36 forces the liquid phase and bubbles to form a forced swirling upward flow. Some bubbles no longer escape rapidly along a straight line, but instead slowly rise along a spiral path, which prolongs the residence time of the bubbles in the liquid phase. This gives the bubbles a more sufficient opportunity to adsorb suspended impurities, tiny solid particles and light phase pollutants in the liquid phase, thereby improving the impurity capture efficiency.

[0027] The gas-induced crystallization component 33 includes a second liquid phase tube 43. The upper part of the second liquid phase tube 43 is connected to the first liquid delivery tube 39. The upper part of the second liquid phase tube 43 is connected to the second liquid delivery tube 48. A baffle plate 44 is connected in the second liquid phase tube 43. A cooling ring plate 45 is connected inside the second liquid phase tube 43. A high-pressure ammonia injector 46 is connected to the top of the second liquid phase tube 43. The high-pressure ammonia injector 46 is connected to the gas phase circulation mechanism 54. A crystallization temporary storage shell 47 is connected to the bottom of the second liquid phase tube 43. The liquid phase material after being processed by the first liquid phase tube 35 enters the second liquid phase tube 43 through the first liquid delivery tube 39. Specifically, the liquid phase material enters from the upper part of the second liquid phase tube 43. Under the action of the baffle plate 44, the liquid phase material flows downward around the baffle plate 44 and rises again before it can be discharged into the third liquid phase tube 49 through the second liquid delivery tube 48. During this process, the high-pressure ammonia injector 46 injects high-pressure ammonia gas, and the cooling ring plate 45 controls the temperature of the liquid material (0 to 5 degrees Celsius). Under the synergistic effect of low temperature environment and high-pressure ammonia gas, the solubility of organic impurities, by-product salts, metal ions and trace solid suspensions with low solubility in the liquid material is significantly reduced, forming a supersaturated system and rapidly precipitating crystals, thereby converting soluble or slightly soluble impurities into separable solid crystalline particles. This process is driven by both rapid cooling and ammonia salting out, with fast crystallization kinetics and high supersaturation. Even in continuous flow, impurity crystallization can be completed in a short residence time. It is particularly important to note that high-pressure ammonia can achieve high concentration dissolution in the system. After a large number of ammonia molecules enter the liquid phase, they will significantly change the solvent polarity and solubility, producing a strong salting-out effect. This causes the solubility of organic impurities, by-product salts, and metal ions to drop sharply, quickly forming a supersaturated state and precipitating crystals. In contrast, atmospheric pressure ammonia has a low partial pressure and limited solubility in the liquid phase, making it difficult to significantly change the system's solubility characteristics and effectively trigger impurity precipitation. A controllable discharge valve plate is provided in the liquid phase tube 2 43 and the crystallization temporary storage shell 47. During normal reaction and flow crystallization, the discharge valve plate is in the closed state, blocking the connection between the liquid phase tube 2 43 and the crystallization temporary storage shell 47. The material flows downward and then back upward under the action of the flow baffle plate 44, forming an upward liquid flow. At this time, the precipitated crystal particles will be suspended in the lower conical cavity of the liquid phase tube 2 43 and will not fall into the crystallization temporary storage shell 47. When it is necessary to discharge slag and clean crystals, first stop the liquid phase feed, close the high-pressure ammonia injector 46, and after the flow in the pipe stops, open the discharge valve plate. The crystal particles that have lost the upward liquid flow support will automatically fall into the crystallization temporary storage shell 47 under the action of gravity and be collected in a concentrated manner, thus completing the staged discharge of impurity crystals.

[0028] The liquid phase feeding component 34 includes a liquid phase tube 3 49. The upper part of the liquid phase tube 3 49 is connected to the liquid delivery tube 2 48. A microporous filter membrane 50 is connected in the liquid phase tube 3 49. A re-filter tube 51 is connected in the middle of the liquid phase tube 3 49. The other end of the re-filter tube 51 is connected to the liquid inlet tube 38 of the liquid phase gas separation component 32. A liquid phase feeding tube 53 is connected to the lower part of the liquid phase tube 3 49. The other end of the liquid phase feeding tube 53 is connected to the top of the reaction tank 2. An ammonia backflush device 52 is connected to the bottom of the liquid phase tube 3 49. The ammonia backflush device 52 is connected to the gas phase circulation mechanism 54. The clean liquid phase material after being processed by the liquid phase tube 2 43 will enter the liquid phase tube 3 49 through the liquid delivery tube 2 48. At this time, the liquid phase material flows on the microporous filter membrane 50. Most of the liquid phase material is filtered again by the microporous filter membrane 50 and then enters the reaction tank 2 through the liquid phase feeding tube 53 to complete the feeding. During this process, some liquid phase material will return to the inlet pipe 38 through the re-filter tube 51 above the microporous filter membrane 50 and re-enter the liquid phase tube 35 for re-filtration. It is important to note that these returning liquid phase materials form a tangential sweeping flow along the surface of the microporous filter membrane 50, which washes away and removes the impurity particles trapped on the surface of the microporous filter membrane 50, and carries the impurities back to the inlet pipe 38 through the re-filter tube 51 and re-enters the liquid phase tube 35 for processing. By combining cross-flow filtration with recirculation, impurities trapped on the surface of the microporous filter membrane 50 can be continuously cleaned, preventing clogging and achieving continuous, stable, and long-lasting deep filtration and purification. Before each liquid phase feed, the microporous filter membrane 50 is backflushed by an ammonia backflushing device 52. High-pressure ammonia gas penetrates the micropores from the bottom up, forcefully stripping and blowing away the fine crystals, solid impurities, and attached contaminants that are clogging the filter pores to the upper surface of the microporous filter membrane 50. This restores the pores of the microporous filter membrane 50 to unobstructed flow, preventing clogging and reduced throughput caused by residual impurities from the previous operation. After the ammonia backflushing is completed and the surface of the microporous filter membrane 50 is enriched with the stripped impurities, the liquid phase feed process is started. As the liquid material flows along the surface of the microporous filter membrane 50, it can directly carry away the impurities concentrated on the upper surface of the microporous filter membrane 50 after backflushing, and return them to the front-end pipeline through the re-filter pipe 51 for cyclone impurity removal, low-temperature crystallization, and bubble flotation treatment.

[0029] By combining pre-flushing ammonia gas to unclog micropores and liquid-phase cross-flow sweeping to remove impurities, the microporous filter membrane 50 achieves online automatic cleaning and long-term anti-clogging, ensuring filtration accuracy without the need for machine shutdown for disassembly and cleaning, significantly improving the stability of continuous equipment operation, and reducing the frequency of consumable replacement and maintenance costs.

[0030] The liquid phase feeding mechanism 31 of this application utilizes recovered ammonia gas to perform flotation and crystallization of liquid phase raw materials, abandoning the traditional filter cartridge-type impurity removal structure. It eliminates the need for filter cartridge consumables, and avoids filter cartridge clogging, attenuation, and failure. This solves the problems of traditional processes that use filter cartridges for liquid phase impurity removal, such as easy filter cartridge clogging, frequent shutdowns for replacement, difficulty in cleaning deep-seated impurities, high consumable costs, and poor production continuity. It is beneficial to improve the practical performance of the mixing and heating reaction equipment and reduce operating costs.

[0031] Please see Figure 9 The testing unit 61 includes a sampling head 62, a chromatograph 67, and a waste liquid tank 68. The sampling head 62 is connected to the reaction vessel 2. One end of the sampling head 62 is connected to a sampling tube 63. A metering pump 64 is installed on the sampling tube 63. One end of the sampling tube 63 is connected to a detection delivery tube 65 and a waste liquid delivery tube 66. The detection delivery tube 65 is connected to the chromatograph 67, and the waste liquid delivery tube 66 is connected to the waste liquid tank 68. At the same time, one end of the foam overflow tube 40 is also connected to the waste liquid tank 68. During normal testing, the metering pump 64 starts according to the set flow rate and time cycle, generating a stable suction negative pressure, which draws the liquid phase material in the reaction vessel 2 into the sampling tube 63 through the sampling head 62, realizing quantitative and timed automatic online sampling without the need for manual opening of the lid for sampling, thus avoiding ammonia leakage and material contamination. The sampled liquid material is transported in two routes: one route is precisely fed into the chromatograph 67 via the detection and delivery pipe 65, where the chromatograph 67 performs component analysis on the sample, rapidly determining the reactant conversion rate, target product content, and impurity residual concentration. The detection data is fed back to the control system in real time to adjust the reaction temperature, ammonia flow rate, and material ratio; the other route carries pipeline residual liquid, cleaning waste liquid, and chromatographic detection waste liquid, which is transported in a closed manner via the waste liquid delivery pipe 66 to the waste liquid tank 68 for centralized storage and subsequent unified harmless treatment, preventing the direct discharge of waste liquid containing ammonia and organic solvents, which could cause environmental pollution and safety hazards. After a single test is completed, the system can use the built-in cleaning function of the pipeline to clean the residual liquid in the sampling tube 63 and the test delivery tube 65, so as to avoid sample residue causing distortion in the next test and ensure that the test results are continuous, accurate and reliable. It should be further explained that the chromatograph 67 is based on the principle of the difference in the partition coefficient of substances between the stationary phase and the mobile phase to achieve the separation and quantitative detection of each component in the reaction solution. It is used to monitor the reaction conversion rate, product purity and impurity content of piperazine / pharmaceutical intermediates in real time. The chromatograph 67 is a conventional and well-known technology. Those skilled in the art can and should understand its specific functions and structure, so it will not be described in detail here.

[0032] The top of the reaction vessel 2 is connected to several vessel interfaces 202, and the bottom of the reaction vessel 2 is connected to a discharge pipe 203. One side of the temperature control jacket 201 is connected to several jacket interfaces 204. The vessel interfaces 202 are mainly used for the installation interfaces of monitoring instruments such as pressure sensors and temperature sensors; safety pressure relief, backup feeding and maintenance interfaces; the discharge pipe 203 is used to discharge the finished product after the reaction, realizing the collection of products and subsequent process transportation; the jacket interfaces 204 are mainly used for the power cord lead-out interface of the electric heating component, for external power supply and temperature control circuit connection; the temperature sensor installation interface inside the jacket, to collect the jacket heating temperature in real time, and to achieve precise temperature control in conjunction with PID; and the heat insulation sealing and maintenance interface, for the maintenance and sealing protection of internal electrical components, etc.

[0033] When using this invention: First, reaction vessel 2 is the core reaction chamber for the preparation of pharmaceutical intermediates. It is the main place for the synthesis reaction of piperazine / pyrazine pharmaceutical intermediates. Liquid materials, ammonia and solid catalysts are mixed, contacted, heated and amination cyclization reactions are completed inside reaction vessel 2 to finally generate the target pharmaceutical intermediate. Reaction vessel 2 adopts a closed pressure-bearing structure, which can provide a stable and safe reaction space for gas, liquid and solid three-phase reaction under high temperature and high pressure, while ensuring that the materials are fully stirred and mixed inside, improving the reaction conversion rate and product selectivity. Secondly, the gas phase circulation mechanism 54 recovers the excess ammonia gas after the reaction in the reaction tank 2. After recovery, it can be reinjected into the solid-liquid mixture through the microporous aerator 55 for further reaction. Alternatively, the recovered ammonia gas can be supplied to the solid phase feeding mechanism 4 and the liquid phase feeding mechanism 31. The circulating ammonia gas can be used to pre-treat the solid phase material without the need for a mechanical transmission structure. It can also be used to treat the liquid phase material without the need for a traditional filter structure. Specifically, after the recovered ammonia gas is extracted from the gas phase space at the top of the reaction tank 2, it first enters the ammonia purification box 59. After multi-stage purification, the impurity content of the ammonia gas is significantly reduced, and its purity is stable enough to meet the reaction requirements. It is then reinjected into the reaction tank 2 to participate in the reaction or supplied to the solid phase feeding mechanism 4 and the liquid phase feeding mechanism 31. This achieves closed-loop circulation, efficient reuse, and continuous stability of ammonia gas, which improves the utilization rate of raw materials and ensures the long-term stable operation of the reaction system. Then, the anti-bridging section 6 of the solid-phase feeding mechanism 4 is located at the uppermost end of the feed pipe 5. The working air of all the conical nozzles 13 will form an annular air curtain along the inner wall of the truncated cone ring 11. This air curtain flows closely against the inner wall, which is equivalent to forming a dynamic gas isolation layer between the material and the wall. When the solid catalyst particles fall along the inner wall of the truncated cone ring 11, the particles first contact the air curtain, rather than directly contacting the metal wall. The airflow has a lifting and guiding effect on the particles, keeping the material in a suspended flow state and avoiding direct contact and friction between the particles and the wall. On the other hand, the high-speed airflow continuously sweeps the inner wall, which can promptly remove the adhesion caused by humidity and static electricity, and destroy the particle agglomeration and the material adhering to the wall. The formation conditions are thus fundamentally avoided, thus avoiding problems such as solid material adhesion, bridging, scaling, and blockage, ensuring smooth, uniform, and continuous feeding. The inclined air nozzle 19 blows ammonia gas to the outer arc plate 18 of the suspension impeller 15 to drive the suspension impeller 15 to rotate. At the same time, the inclined swirling air ring 16 also sprays the purified circulating ammonia gas at high speed from the left swirling nozzle 17 to form a left swirling flow field. The two work together to drive the suspension impeller 15 to rotate at high speed. It is completely driven by no additional electricity, perfectly adapted to the cleanroom scenario of medicine, and uses circulating ammonia gas, without the need for an additional gas source. It then performs shearing and crushing work on the solid material. At the same time, the rotation of the suspension impeller 15 will also pull the material to flow downward continuously for feeding. Furthermore, the material crushed by the suspended impeller 15 enters the converging part 20 with the airflow. The converging part 20 is a Venturi channel, which forms a strong negative pressure zone at the throat, accelerating the material into a high-speed material stream. The high-pressure ammonia gas ejected from the high-pressure fluidized nozzle 22 mixes thoroughly with the material stream in the negative pressure zone, instantly dispersing the material stream into a fluidized gas-solid two-phase flow. This completely fluidizes and dissolves the soft agglomerates and bridging structures between material particles, achieving deep deagglomeration. Then, under the deceleration effect of the Venturi diffuser section of the converging part 20, the fluidized material can be smoothly conveyed downwards without turbulence, back-mixing, or wall adhesion, ensuring continuous and stable feeding without any stagnation in the feed pipe 5. The fluidized and deagglomerated material enters the pulse section 9, where the left-hand rotating air ring 23 and the right-hand rotating air ring 24, in conjunction with the tilted electromagnetic pulse nozzle 25, form a high-frequency oscillating axial shear flow field within the pipe, rather than a radial counter-current field. This avoids the material being blown back and blocking the pipe, while also creating a high-intensity reciprocating shear. In a high-frequency oscillating flow field, the material is repeatedly sheared, collided, and dispersed. The remaining micron-sized soft agglomerates and microcrystalline agglomerates are completely broken into monodisperse uniform powders, achieving final agglomeration and ensuring that the material entering the reaction tank 2 is free of any agglomeration structure. The processed uniform solid material will reach the guide ring 26. The gas distribution ring 3 27 supplies gas to the check nozzle 28, so that the check nozzle 28 blows air downward above the guide ring 26 to prevent the humid hot ammonia gas and solvent vapor in the reaction tank 2 from flowing back into the feed pipe 5. At the same time, several diffusion nozzles 30 work in sequence to moderately purge the solid material entering the reaction tank 2, so that the solid material can enter the reaction tank 2 in a dispersed manner for reaction. This effectively improves the problem of local accumulation and uneven distribution of solid material after feeding, fully exposes the catalytic active sites of solid material, improves reaction conversion rate and product selectivity, and reduces local reaction overheating and increased side reactions caused by material agglomeration, ensuring that the reaction process is stable and efficient. In addition, the inlet pipe 38 of the liquid phase feeding mechanism 31 introduces liquid phase material tangentially into the liquid phase pipe 35, where the liquid phase material forms a rotating vortex. At this time, the spiral baffle 36 guides and constrains the tangentially entering rotating liquid flow, causing the material to continuously advance along the spiral path, avoiding vortex attenuation, maintaining a stable centrifugal rotation state, and enhancing the internal disturbance of the liquid phase. Simultaneously, when the bubble generator 37 is working, it uses the recycled ammonia gas to introduce a large number of uniform microbubbles into the liquid phase. These microbubbles, during their ascent, will absorb... Suspended solid impurities, trace amounts of oil, catalyst powder, by-product flocculents, and other hydrophobic or weakly surface-active particles in the liquid phase adhere to the surface of the bubbles and float to the liquid surface with the bubbles. They eventually accumulate at the top of the liquid phase to form a foam layer. At this time, the gas supply ring 41 supplies the ammonia gas recovered by the gas phase circulation mechanism 54 to the purge nozzle 42. The purge nozzle 42 can blow the foam layer accumulated at the top of the liquid phase toward the foam overflow pipe 40. These foam layers with impurities will flow into the waste liquid tank 68 through the foam overflow pipe 40. Finally, the liquid material processed by liquid phase tube 35 enters liquid phase tube 43 through liquid delivery tube 39. Specifically, the liquid material enters from the top of liquid phase tube 43, and under the action of baffle plate 44, it flows downwards around the baffle plate 44 and rises again before being discharged into liquid phase tube 49 through liquid delivery tube 48. During this process, high-pressure ammonia injector 46 injects high-pressure ammonia gas, and cooling ring plate 45 controls the temperature of the liquid material (0 to 5 degrees Celsius). Under the synergistic effect of low temperature environment and high-pressure ammonia gas, organic impurities with low solubility, by-product salts, metal ions, and trace solid suspended matter in the liquid material are eliminated. The solubility of the impurities is significantly reduced, forming a supersaturated system and rapidly precipitating crystals, thereby converting soluble or slightly soluble impurities into separable solid crystalline particles. This process is driven by both rapid cooling and ammonia salting out, resulting in fast crystallization kinetics and high supersaturation. Even in continuous flow, impurities can be crystallized and precipitated within a short residence time. The clean liquid material after being treated by liquid phase tube 2 43 will enter liquid phase tube 3 49 through liquid delivery tube 2 48. At this time, the liquid material flows on the microporous filter membrane 50. Most of the liquid material is filtered again through the microporous filter membrane 50 and then enters the reaction tank 2 through the liquid phase feeding tube 53 to complete the feeding. During this process, some liquid material will return to the inlet pipe 38 via the re-filter tube 51 above the microporous filter membrane 50 and re-enter the liquid phase pipe 35 for re-filtration. It is important to note that this returning liquid material forms a tangential sweeping flow along the surface of the microporous filter membrane 50, washing away and removing impurity particles trapped on the surface of the microporous filter membrane 50. These impurities are then carried back through the re-filter tube 51 to the inlet pipe 38 and re-enter the liquid phase pipe 35 for processing. By combining cross-flow filtration with recirculation, impurities trapped on the surface of the microporous filter membrane 50 can be continuously cleaned, preventing clogging and achieving continuous, stable, and long-lasting deep filtration purification. Furthermore, before each liquid phase feed, the material is backflushed by an ammonia gas backflushing device 52. The microporous filter membrane 50 is backflushed. High-pressure ammonia gas penetrates the micropores from the bottom up, forcefully stripping away and blowing away the fine crystals, solid impurities, and attached contaminants that are blocking the filter pores to the upper surface of the microporous filter membrane 50. This restores the pores of the microporous filter membrane 50 to unobstructed flow, preventing filter membrane blockage and reduced throughput caused by residual impurities from the previous operation. After the ammonia backflushing is completed and the surface of the microporous filter membrane 50 is enriched with the stripped impurities, the liquid phase feeding process is started. When the liquid material flows along the surface of the microporous filter membrane 50, it can directly carry away the impurities that are concentrated on the upper surface of the microporous filter membrane 50 after backflushing, and return them to the front end pipeline through the re-filter pipe 51 for cyclone impurity removal, low-temperature crystallization, and bubble flotation treatment. By combining pre-flushing ammonia gas to unclog micropores and liquid-phase cross-flow sweeping to remove impurities, the microporous filter membrane 50 achieves online automatic cleaning and long-term anti-clogging, ensuring filtration accuracy without the need for machine shutdown for disassembly and cleaning, significantly improving the stability of continuous equipment operation, and reducing the frequency of consumable replacement and maintenance costs.

[0034] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates, comprising a workbench (1) and a reaction vessel (2) mounted on one side of the workbench (1), characterized in that: The reaction vessel (2) is equipped with a temperature control jacket (201), a stirring component (3) is installed on the reaction vessel (2), a solid phase feeding mechanism (4) is connected to the reaction vessel (2), a liquid phase feeding mechanism (31) is connected to the reaction vessel (2), a gas phase circulation mechanism (54) is connected to the reaction vessel (2), and a detection mechanism (61) is provided on one side of the reaction vessel (2); the solid phase feeding mechanism (4) includes a feed pipe (5), and a gas supply diversion pipe is provided on the outside of the feed pipe (5). The gas phase circulation mechanism (54) is connected to the gas supply diversion pipe for gas supply. The feed pipe (5) is provided with an anti-bridging section (6), a clump breaking section (7), a flow section (8), a pulse section (9), and a check-diffusion section (10). The liquid phase feeding mechanism (31) includes a liquid phase gas separation component (32), a gas-induced crystallization component (33), and a liquid phase feeding component (34). The gas phase circulation mechanism (54) is connected to the liquid phase gas separation component (32), the gas-induced crystallization component (33), and the liquid phase feeding component (34) for gas supply.

2. The synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates according to claim 1, characterized in that: The anti-bridging section (6) is provided with a truncated cone ring (11), the top of which is connected to a distribution ring (12), and the bottom of which is connected to several conical nozzles (13). The bridging section (7) is provided with a receiving ring (14), which is provided with a sliding groove. A suspended impeller (15) is provided in the receiving ring (14), and the outer side of the suspended impeller (15) is slidably connected to the sliding groove. A slanted vortex air ring (16) is provided above the suspended impeller (15), and the bottom of the slanted vortex air ring (16) is connected to several left-handed nozzles (17). An arc plate (18) is connected to the outer side of the suspended impeller (15). Several slanted air nozzles (19) are connected to the receiving ring (14). The distribution ring (12), the slanted vortex air ring (16), and the slanted air nozzles (19) are all connected to the air supply diversion pipe.

3. The synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates according to claim 2, characterized in that: The flow section (8) is provided with a contraction element (20), and a second gas distribution ring (21) is provided above the contraction element (20). Several high-pressure flow nozzles (22) are connected to the bottom of the second gas distribution ring (21). The high-pressure flow nozzles (22) mix with the solid material to form a high-speed material flow stream. The pulse section (9) is provided with a left-handed gas ring (23) and a right-handed gas ring (24). The left-handed gas ring (23) and the right-handed gas ring (24) are circumferentially distributed. Several electromagnetic pulse nozzles (25) are connected to the bottom of the left-handed gas ring (23) and the right-handed gas ring (24). The electromagnetic pulse nozzles (25) work on the material falling path to form a strong shear turbulence layer. The second gas distribution ring (21), the left-handed gas ring (23), and the right-handed gas ring (24) are all connected to the gas supply diversion pipe.

4. The synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates according to claim 3, characterized in that: The check-back diffuser section (10) is provided with a guide ring (26), and a gas distribution ring three (27) is installed on the guide ring (26). Several check-back nozzles (28) are connected to the bottom of the gas distribution ring three (27). A gas distribution ring four (29) is provided below the guide ring (26). Several diffuser nozzles (30) are connected to the inner side of the gas distribution ring four (29). The several diffuser nozzles (30) work in sequence. Both the gas distribution ring three (27) and the gas distribution ring four (29) are connected to the gas supply split pipe.

5. The synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates according to claim 1, characterized in that: The gas phase circulation mechanism (54) includes a microporous aerator (55), which is installed at the bottom of the reaction tank (2). The bottom of the microporous aerator (55) is connected to an air inlet pipe (56) and a circulation pipe (57). The air inlet pipe (56) is connected to an external ammonia supply device. One end of the circulation pipe (57) is connected to the top of the reaction tank (2) and passes through the top of the reaction tank (2). A collection head (58) is provided at the top of the inner part of the reaction tank (2). One end of the circulation pipe (57) is connected to the collection head (58). An ammonia purification box (59) is connected on the workbench (1). The ammonia purification box (59) is connected to the circulation pipe (57). A gas supply pipe (60) is connected to one side of the ammonia purification box (59). The gas supply pipe (60) provides the recovered ammonia to the solid phase feeding mechanism (4) and the liquid phase feeding mechanism (31).

6. The synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates according to claim 1, characterized in that: The liquid phase gas separation component (32) includes a liquid phase tube (35), a spiral baffle (36) connected in the liquid phase tube (35), a bubble generator (37) connected to the bottom of the liquid phase tube (35), an inlet pipe (38) connected to the middle of the liquid phase tube (35), a delivery pipe (39) connected to the lower part of the liquid phase tube (35), a foam overflow pipe (40) connected to the upper part of the liquid phase tube (35), an air supply ring (41) connected to the upper part of the liquid phase tube (35), and several purge nozzles (42) connected to one side of the air supply ring (41). The bubble generator (37) and the air supply ring (41) are both connected to the gas phase circulation mechanism (54).

7. The synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates according to claim 6, characterized in that: The gas-induced crystallization component (33) includes a second liquid phase tube (43), the upper part of which is connected to a first liquid delivery tube (39), the upper part of which is connected to a second liquid delivery tube (48), a baffle plate (44) connected in the second liquid phase tube (43), a cooling ring plate (45) connected inside the second liquid phase tube (43), a high-pressure ammonia injector (46) connected to the top of the second liquid phase tube (43), the high-pressure ammonia injector (46) connected to the gas phase circulation mechanism (54), and a crystallization temporary storage shell (47) connected to the bottom of the second liquid phase tube (43).

8. The synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates according to claim 7, characterized in that: The liquid phase feeding component (34) includes a liquid phase tube three (49), the upper part of which is connected to the liquid delivery tube two (48), a microporous filter membrane (50) is connected in the liquid phase tube three (49), a re-filter tube (51) is connected in the middle of the liquid phase tube three (49), the other end of the re-filter tube (51) is connected to the liquid inlet pipe (38) of the liquid phase gas separation component (32), the lower part of the liquid phase tube three (49) is connected to a liquid phase feeding tube (53), the other end of the liquid phase feeding tube (53) is connected to the top of the reaction tank (2), the bottom of the liquid phase tube three (49) is connected to an ammonia backflush device (52), and the ammonia backflush device (52) is connected to the gas phase circulation mechanism (54).

9. The synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates according to claim 1, characterized in that: The detection mechanism (61) includes a sampling head (62), a chromatograph (67), and a waste liquid tank (68). The sampling head (62) is connected to the reaction vessel (2). One end of the sampling head (62) is connected to a sampling tube (63). A metering pump (64) is installed on the sampling tube (63). One end of the sampling tube (63) is connected to a detection delivery tube (65) and a waste liquid delivery tube (66). The detection delivery tube (65) is connected to the chromatograph (67), and the waste liquid delivery tube (66) is connected to the waste liquid tank (68).

10. The synthetic reaction apparatus for piperazine-pyrazine pharmaceutical intermediates according to claim 1, characterized in that: The top of the reaction vessel (2) is connected to several vessel interfaces (202), the bottom of the reaction vessel (2) is connected to a discharge pipe (203), and one side of the temperature control jacket (201) is connected to several jacket interfaces (204).

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