An intermediate microchannel reactor preparation device

Abstract

The utility model discloses an intermediate micro -channel reaction preparation device relates to the field of pharmaceutical intermediates production, including first branch pipeline, second branch pipeline and third branch pipeline, three parallelly arranged, the pre -cooler of first branch pipeline with the pre -cooler of second branch pipeline is connected through static mixer, makes first medicament with second medicament mixed and dissolved in this static mixer, and the liquid after mixing is transported to the micro -channel reactor connected in static mixer rear, the liquid formed after first medicament with second medicament mix forms and third medicament in micro -channel reactor mixed reaction, dissolves, and enters the tubular reactor connected in micro -channel reactor rear, and tubular reactor rear sets up medicament mixing export, is used for connecting to subsequent dosing point. The utility model can carry out efficient continuous, process accurate control to solve the problem such as low production efficiency, relatively big energy consumption, product quality is not consistent etc.

Description

Technical Field

[0001] This utility model relates to the field of pharmaceutical intermediate production, specifically to an intermediate microchannel reaction preparation device. Background Technology

[0002] Currently, the production and preparation of pharmaceutical intermediates mostly utilizes high-temperature reactors. These reactors have inlets and outlets on the outside and an internal stirring mechanism. The reactor body is electrically raised and lowered and can be heated. Solid or liquid media are directly added to the reactor for heating and pressurization mixing. The reactor is controlled by a touchscreen, allowing for a customizable interface to monitor the stirring equipment and record data.

[0003] However, existing technologies have the following drawbacks: 1. Low production efficiency and discontinuous operation: Each production cycle includes steps such as feeding, reaction, cooling and discharging. These auxiliary steps take up a lot of time and are labor-intensive. Each reaction requires recooling of the reactor, resulting in high energy consumption. Moreover, the equipment does not carry out effective chemical reactions during each feeding operation, resulting in low equipment utilization. 2. Each batch is independent, and product quality varies: Each reactor is an independent batch. Even with strict control of process parameters, the product quality between batches will be different. There may be mixing dead zones or concentration / temperature gradients in large reactors, which may cause slight differences in the quality of the product at different locations in the same reactor. It is impossible to guarantee that the product quality is completely consistent. 3. Weak control over exothermic / endothermic reactions: For violently exothermic reactions, all reactants are added at once, and heat is released in a concentrated manner in a short period of time; the heat transfer area of ​​the reactor is relatively small compared to the reaction volume, which can easily lead to safety accidents or side reactions. In addition, the temperature is a variable value throughout the reaction process, making it impossible to precisely control the reaction temperature.

[0004] 4. Relatively concentrated safety risks: All materials in the entire reaction cycle are concentrated in the same container. Once an uncontrolled reaction, leakage or explosion occurs, the consequences are often very serious. Operators need to frequently come into contact with the equipment interface, which increases the risk of hazardous chemicals or operational errors. Utility Model Content

[0005] The purpose of this invention is to overcome the shortcomings of the existing technology and provide an intermediate microchannel reaction preparation device that can perform efficient and continuous, precise process control to solve problems such as low production efficiency, high energy consumption, and inconsistent product quality.

[0006] The purpose of this utility model is achieved through the following technical solution: This intermediate microchannel reaction preparation device includes a first branch pipeline, a second branch pipeline and a third branch pipeline, which are arranged in parallel. The first branch pipeline is provided with a chemical inlet A at one end for injecting the first chemical agent. The chemical inlet A is connected to the cold insulation pipeline and enters the dosing pump after passing through a set of pneumatic control valves. The dosing pump is used to pressurize the first chemical agent. The pressurized first chemical agent flows along the first branch pipeline through a set of temperature and pressure transmitter valves and is then connected to a precooler. The second branch pipeline is equipped with a chemical inlet B at one end for injecting the second chemical agent. The chemical inlet B is connected to the cold insulation pipeline and enters the dosing pump after passing through a set of pneumatic control valves. The dosing pump is used to pressurize the second chemical agent. The pressurized second chemical agent flows along the second branch pipeline through a set of temperature and pressure transmitter valves and then connects to a precooler. The precooler of the first branch pipeline and the precooler of the second branch pipeline are connected through a static mixer, so that the first agent and the second agent are mixed and dissolved in the static mixer, and the mixed liquid is transported to the microchannel reactor connected to the downstream of the static mixer. The third branch pipeline is provided with a reagent inlet C at one end for injecting the third reagent. The reagent inlet C is connected to the cold insulation pipeline and enters the dosing pump after passing through a set of pneumatic control valves. The dosing pump is used to pressurize the third reagent. The pressurized third reagent flows along the third branch pipeline through a set of temperature and pressure transmitter valves and is then connected to a precooler. The precooler delivers the third reagent into the microchannel reactor. The liquid formed by mixing the first and second reagents is mixed and reacted with the third reagent in a microchannel reactor, and then enters a tubular reactor connected to the microchannel reactor. A reagent mixing outlet is provided at the rear of the tubular reactor for connection to subsequent dosing points.

[0007] As a further technical solution, the pneumatic control valve group includes a pipeline pressure gauge, a basket filter and a pneumatic switching valve A arranged in sequence. The basket filter, the pneumatic switching valve A and the dosing pump are all arranged in parallel with two sets of equipment, and the two sets serve as backups for each other.

[0008] As a further technical solution, the temperature and pressure transmitting valve group includes a flow meter, a pressure transmitter A, a temperature transmitter A, and a pneumatic switching valve B arranged in sequence.

[0009] As a further technical solution, a pressure transmitter B, a temperature transmitter B, a pneumatic diaphragm regulating valve, and a pneumatic switching valve C are sequentially installed on the pipeline between the tubular reactor and the reagent mixing outlet.

[0010] As a further technical solution, the precooler, static mixer, microchannel reactor and tubular reactor all adopt pneumatic thin-film regulating valves to automatically connect to the cold insulation medium to ensure the required temperature conditions of the medium.

[0011] As a further technical solution, the first reagent is dichloromethane, the second reagent is diethylamine, and the third reagent is hexachloropropene.

[0012] As a further technical solution, the dosing pump can be a metering pump, electromagnetic pump, digital pump, or hose pump, and the dosing pump can receive control signals through a frequency converter to achieve automated dosing control.

[0013] As a further technical solution, the shell sides of the tubular reactor, static mixer, and each precooler are all connected to a temperature control unit.

[0014] The beneficial effects of this utility model are as follows: 1. A combination of a dosing pump, a precooler, a static mixer, a microchannel reactor, and a tubular reactor is used for the mixing and preparation of pharmaceutical intermediates. The skid-mounted design allows for continuous operation with no downtime between batches, enabling 24-hour continuous output. It is suitable for large-scale production, has high production efficiency, and solves the problems of low production efficiency and discontinuous operation of reaction vessels. 2. By precisely controlling the process and reaction conditions, we ensure minimal batch-to-batch differences and stable, uniform product quality, thus solving the problem of product quality variation. 3. By using a microchannel reactor, the heat of reaction can be effectively removed by controlling the flow rate and enhancing cooling, avoiding heat accumulation that could cause the reactor to overheat and lead to side reactions. This enhances the exothermic reaction process and temperature control capabilities, resulting in a higher degree of automation and solving the problem of not being able to accurately control the reaction temperature. 4. Compared to the total amount of material in the reactor, the amount of reactants held per unit volume per unit time is relatively small. Parameters such as feed, discharge, temperature, pressure, and flow rate are all automatically controlled and monitored, reducing the frequency of personnel operation and contact with the medium, reducing risks and operational errors, and solving the problem of relatively concentrated safety risks. 5. Add monitoring instruments and automatic valves during the preparation process to improve automation, reduce manual labor intensity, and reduce energy consumption. Attached Figure Description

[0015] Figure 1 This is a schematic diagram of the structure of this utility model.

[0016] Explanation of reference numerals in the attached diagram: Chemical inlet A1, Chemical inlet B2, Chemical inlet C3, Cold insulation pipe 4, Basket filter 5, Pneumatic switch valve A6, Dosing pump 7, Flow meter 8, Pressure transmitter A9, Temperature transmitter A10, Pneumatic switch valve B11, Precooler 12, Static mixer 13, Microchannel reactor 14, Tubular reactor 15, Pressure transmitter B16, Temperature transmitter B17, Pneumatic diaphragm regulating valve 18, Pneumatic switch valve C19, Chemical mixing outlet 20. Detailed Implementation

[0017] The present invention will now be described in detail with reference to the accompanying drawings: Example: As attached Figure 1 As shown, this intermediate microchannel reaction preparation device includes a reagent inlet A1, a reagent inlet B2, a reagent inlet C3, a cold insulation pipe 4, a basket filter 5, a pneumatic switch valve A6, a dosing pump 7, a flow meter 8, a pressure transmitter A9, a temperature transmitter A10, a pneumatic switch valve B11, a precooler 12, a static mixer 13, a microchannel reactor 14, a tubular reactor 15, a pressure transmitter B16, a temperature transmitter B17, a pneumatic diaphragm regulating valve 18, a pneumatic switch valve C19, and a reagent mixing outlet 20.

[0018] The device has three parallel branch pipelines: the first branch pipeline, the second branch pipeline, and the third branch pipeline. The first branch pipeline has a reagent inlet A1 at one end, through which the first reagent is injected. The first branch pipeline downstream of reagent inlet A1 is insulated (i.e., connected to the insulated pipeline 4), and after passing through a set of pneumatic control valves (including a pipeline pressure gauge, a basket filter 5, and a pneumatic switch valve A6 arranged in sequence), it enters the dosing pump 7. The dosing pump 7 pressurizes the first reagent, which then flows along the first branch pipeline through a set of temperature and pressure transmitter valves (including a flow meter 8, a pressure transmitter A9, a temperature transmitter A10, and a pneumatic switch valve B11 arranged in sequence), and then connects to a precooler 12 (connected to the pipe side of the precooler 12). Preferably, the dosing pump 7 can be a metering pump, electromagnetic pump, digital pump, hose pump, or other types. Furthermore, the dosing pump 7, through a matching frequency converter or an intelligent dosing pump, receives signals from a PLC or host computer to adjust the dosing amount, thereby achieving automated control. Further, the pneumatic control valve group includes a pipeline pressure gauge, a basket filter 5, and a pneumatic switching valve A6 arranged sequentially. The basket filter 5, pneumatic switching valve A6, and dosing pump 7 are all arranged in parallel with two sets (one for use and one for backup), with each set serving as a backup for the other. If the working pump fails, the backup pump can be directly put into production without shutdown. The faulty equipment can be repaired and replaced at an appropriate time, achieving unattended operation.

[0019] Furthermore, a chemical inlet B2 is provided at one end of the second branch pipeline. The second chemical agent is injected into the second branch pipeline through the chemical inlet B2. The second branch pipeline after the chemical inlet B2 is insulated (i.e. connected to the insulated pipeline 4), and after passing through a set of pneumatic control valves, it enters the dosing pump 7. The dosing pump 7 is used to pressurize the second chemical agent. The pressurized second chemical agent flows along the second branch pipeline through a set of temperature and pressure transmitter valves, and then connects to the second precooler 12.

[0020] The precooler 12 of the first branch pipeline and the precooler 12 of the second branch pipeline are connected through a static mixer 13, so that the first agent and the second agent are mixed and dissolved in the static mixer 13. The mixed liquid is then transported to the microchannel reactor 14, which is connected to the downstream of the static mixer 13 through a pipeline.

[0021] A reagent inlet C3 is installed at one end of the third branch pipeline. The third reagent is injected into the third branch pipeline through inlet C3. The third branch pipeline downstream of inlet C3 is insulated (i.e., connected to insulated pipeline 4), and after passing through a set of pneumatic control valves, it enters the dosing pump 7. The dosing pump 7 pressurizes the third reagent, which then flows along the third branch pipeline through a set of temperature and pressure transmitter valves, and then connects to the third precooler 12. The precooler 12 delivers the third reagent into the microchannel reactor 14. Further, the liquid formed by mixing the first and second reagents reacts and dissolves with the third reagent in the microchannel reactor 14, and then enters the tubular reactor 15. The tubular reactor 15 is connected downstream of the microchannel reactor 14, and a reagent mixing outlet 20 is installed downstream of the tubular reactor 15. This reagent mixing outlet 20 can be connected to subsequent dosing points.

[0022] Preferably, a pressure transmitter B16, a temperature transmitter B17, a pneumatic diaphragm regulating valve 18, and a pneumatic switching valve C19 are sequentially installed on the pipeline between the tubular reactor 15 and the reagent mixing outlet 20.

[0023] Preferably, the precooler 12, static mixer 13, microchannel reactor 14 and tubular reactor 15 are all automatically connected to the cold insulation medium by pneumatic diaphragm regulating valves to ensure the required temperature conditions of the medium, thereby ensuring stable product quality.

[0024] Preferably, the first reagent is dichloromethane, the second reagent is diethylamine, and the third reagent is hexachloropropene.

[0025] Preferably, the shell side of the tubular reactor 15, the static mixer 13, and each precooler 12 is connected to a thermostat.

[0026] Preferably, the microchannel reactor 14 is arranged in five stages, with the second and third stages connected in parallel, the fourth and fifth stages connected in parallel, and the first stage connected in series with the second and third stages and the fourth and fifth stages. By confining the chemical reaction within micrometer-scale (typically 10-500 micrometers) channels, the microchannel reactor significantly increases the specific surface area (mass / heat transfer area per unit volume), thereby achieving precise and efficient control of the reaction process. The fluid flows in a laminar state within the microchannels. Through special channel structure designs (such as T-type, Y-type, and heart-shaped mixers), the fluid is divided into extremely thin sheets (down to the micrometer scale), greatly increasing the contact area between the two reactants. Mass transfer mainly relies on molecular diffusion; due to the extremely short diffusion distance, mixing can be completed within milliseconds. Furthermore, the microchannel reactor has extremely small channel dimensions and a huge specific surface area (reaching 10,000-50,000 m² / m³, 100-1000 times that of traditional reactors). The heat of reaction can be exchanged instantaneously with the outside environment through the channel walls, enabling precise control of the reaction temperature (typically within ±1°C) and virtually eliminating temperature gradients. Microchannel reactors operate in a continuous flow manner; reactants are pumped into the system and flow through the reaction channels at a defined flow rate. By precisely controlling the flow rate and channel length, almost identical residence times can be provided for each reactant molecule. This achieves precise control of reaction time, avoiding over- or under-reaction.

[0027] The core principle of microchannel reactors is to achieve precise and enhanced control of the three key elements of chemical reactions—mass transfer, heat transfer, and residence time—through "micro-space constraints," thereby pushing chemical reactions from "macroscopic and extensive" to "microscopic and refined."

[0028] The role and advantages of microchannel reactors: 1. Intrinsically safe: Due to the extremely small liquid holdup in the reactor (usually only a few milliliters), even under very harsh reaction conditions (high temperature and high pressure), the energy stored in the system is minimal, greatly reducing the risk of safety accidents such as explosions and leaks. This makes it possible to perform some dangerous reactions that would not be carried out in traditional equipment (such as nitration, chlorination, fluorination, and peroxidation). 2. Improve reaction efficiency and product yield: Extremely fast mixing and efficient heat transfer suppress the occurrence of side reactions, allowing the reaction to proceed mainly along the target path, thereby significantly improving product selectivity and yield; 3. Achieve superior process conditions: Due to its high safety profile, reactions can be easily carried out under high temperature and high pressure conditions, thereby accelerating the reaction rate and shortening the production cycle. Many reactions that are difficult to perform under conventional conditions can now be achieved. 4. Stable and controllable product quality: The reaction process (mixing, temperature, time) experienced by each molecule is highly consistent, ensuring extremely stable product quality within and between batches, with excellent reproducibility; 5. Rapid Process Development and Scale-up: Scale-up of microchannel reactors follows the principle of "quantitative scaling," meaning it is achieved by increasing the number of microchannels (e.g., from one channel to 1000 channels in parallel) without changing the reaction conditions within each channel. Therefore, the optimal process parameters obtained on laboratory microchannel devices can be directly used in industrial production, significantly shortening the cycle from R&D to production.

[0029] 6. Green and environmentally friendly: Higher yield means less raw material waste; continuous flow operation reduces solvent consumption and wastewater generation during the cleaning process; precise chemical control also reduces the generation of by-products.

[0030] As an optional technical solution, the dosing pump can also adopt a multi-head pump structure, which can more effectively stabilize the pulse and the flow rate. It can also adopt a double diaphragm form. When one diaphragm ruptures, an alarm signal is issued. The advantage of double diaphragms is that when one diaphragm ruptures, the hydraulic oil in the pump body will not mix with the agent and will not contaminate the dosing agent.

[0031] The pneumatic switching valves used in the pipeline system can be replaced by other types of electric actuators to achieve the switching function, such as solenoid valves, electric butterfly valves, electric ball valves, etc., to add a manual valve operation bypass, so that equipment maintenance can be carried out without stopping the machine when the electric valve fails or is damaged.

[0032] Using cooling water through pipes or other cooling methods to replace the precooler results in less effective cooling than the precooler, while also requiring more space and being inconvenient to install and maintain.

[0033] Static mixing reactors replace microchannel reactors, allowing the medium to be continuously divided and recombined during flow, achieving efficient mixing. They have a compact structure, but their heat transfer capacity depends on the tubular structure and requires a matching heat exchange jacket.

[0034] Dichloromethane metabolizes into carbon monoxide, diethylamine is corrosive, and hexachloropropene is stable but may decompose to produce hydrogen chloride. Environmental ventilation is essential, and gas alarm instruments can be installed in the equipment installation workshop for double protection to ensure personnel safety.

[0035] The working process of this utility model: Dichloromethane is introduced into the first branch pipeline through reagent inlet A1 (insulated by cold insulation pipeline 4), and enters the dosing pump 7 through pipeline pressure gauge, basket filter 5, and pneumatic switch valve A6. It is pressurized and delivered according to the flow rate set by the host computer. Depending on the pump structure type, the dosing pump can be equipped with outlet damper, pipeline safety valve, check valve, and back pressure valve to ensure stable and safe operation of the system. The pressurized dichloromethane flows through flow meter 8, pressure transmitter A9, temperature transmitter A10, pneumatic switch valve B11, precooler 12, and then enters static mixer 13.

[0036] Furthermore, diethylamine is introduced into the second branch pipeline (insulated by the cold-insulating pipeline 4) through the reagent inlet B2. The working process is the same as that of dichloromethane. After being pressurized and transported, the diethylamine enters the static mixer 13 to mix and dissolve with the dichloromethane. The mixed liquid is then transported to the microchannel reactor 14.

[0037] Furthermore, the workflow of hexachloropropylene is the same as that of dichloromethane. After being pressurized and transported, it enters the microchannel reactor 14, where it is mixed and reacted with diethylamine and dichloromethane. After being mixed and cooled by the five-stage microchannel reactor 14, it enters the tubular reactor 15, where it is fully mixed and dissolved again. After being mixed and dissolved, it flows through the pressure transmitter B16, the temperature transmitter B17, the pneumatic diaphragm regulating valve 18, and the pneumatic switching valve C19, and is then added to the designated injection point from the reagent mixing outlet 20.

[0038] Diethylamine and dichloromethane work simultaneously, and the working time of hexachloropropylene is set by the system based on the former two.

[0039] Temperature and pressure transmitters are installed on each branch pipeline to monitor the temperature and pressure changes of each branch pipeline in real time, and the data is uploaded to the central control room for analysis and summarization to ensure the safe and stable operation of the system.

[0040] The precooler 12, static mixer 13, microchannel reactor 14, and tubular reactor 15 are all equipped with pneumatic diaphragm regulating valves to automatically connect to the cold insulation medium, ensuring the required temperature conditions of the medium and thus ensuring stable product quality.

[0041] In addition, the complete set of equipment is equipped with a control cabinet, including a PLC and a touch screen, to automatically control various electrical devices, receive instrument signals, and collect, analyze and compare data in real time.

[0042] It is understood that, for those skilled in the art, any equivalent substitutions or modifications to the technical solutions and inventive concepts of this utility model should fall within the protection scope of the appended claims.

Claims

1. A microchannel reaction preparation apparatus for intermediates, characterized in that: It includes the first branch pipeline, the second branch pipeline, and the third branch pipeline, which are arranged in parallel; The first branch pipeline is provided with a chemical inlet A (1) at one end for injecting the first chemical agent. The chemical inlet A (1) is connected to the cold insulation pipeline (4) and enters the dosing pump (7) after passing through a set of pneumatic control valves. The dosing pump (7) is used to pressurize the first chemical agent. After pressurization, the first chemical agent flows along the first branch pipeline through a set of temperature and pressure transmitter valves and is then connected to a precooler (12). The second branch pipeline is provided with a chemical inlet B (2) at one end for injecting the second chemical agent. The chemical inlet B (2) is connected to the cold insulation pipeline (4) and enters the dosing pump (7) after passing through a set of pneumatic control valves. The dosing pump (7) is used to pressurize the second chemical agent. The pressurized second chemical agent flows along the second branch pipeline through a set of temperature and pressure transmitter valves and then connects to a precooler (12). The precooler (12) of the first branch pipeline and the precooler (12) of the second branch pipeline are connected through a static mixer (13) so that the first agent and the second agent are mixed and dissolved in the static mixer (13) and the mixed liquid is transported to the microchannel reactor (14) connected to the rear of the static mixer (13); The third branch pipeline is provided with a reagent inlet C (3) at one end for injecting the third reagent. The reagent inlet C (3) is connected to the cold insulation pipeline (4) and enters the dosing pump (7) after passing through a set of pneumatic control valves. The dosing pump (7) is used to pressurize the reagent. The pressurized reagent flows along the third branch pipeline through a set of temperature and pressure transmitter valves and is then connected to a precooler (12). The precooler (12) sends the third reagent into the microchannel reactor (14). The liquid formed by mixing the first agent and the second agent is mixed and reacted with the third agent in the microchannel reactor (14), dissolved, and then enters the tubular reactor (15) connected to the back of the microchannel reactor (14). A agent mixing outlet (20) is provided at the back of the tubular reactor (15) for connection to the subsequent dosing point.

2. The intermediate microchannel reaction preparation apparatus according to claim 1, characterized in that: The pneumatic control valve group includes a pipeline pressure gauge, a basket filter (5) and a pneumatic switch valve A (6) arranged in sequence. The basket filter (5), the pneumatic switch valve A (6) and the dosing pump (7) are all arranged in parallel with two sets of equipment, and the two sets are backups for each other.

3. The intermediate microchannel reaction preparation apparatus according to claim 1, characterized in that: The temperature and pressure transmitting valve group includes a flow meter (8), a pressure transmitter A (9), a temperature transmitter A (10), and a pneumatic switching valve B (11) arranged in sequence.

4. The intermediate microchannel reaction preparation apparatus according to claim 1, characterized in that: A pressure transmitter B (16), a temperature transmitter B (17), a pneumatic diaphragm regulating valve (18), and a pneumatic switching valve C (19) are sequentially installed on the pipeline between the tubular reactor (15) and the reagent mixing outlet (20).

5. The intermediate microchannel reaction preparation apparatus according to claim 1, characterized in that: The precooler (12), static mixer (13), microchannel reactor (14) and tubular reactor (15) are all automatically connected to the cold insulation medium using pneumatic thin film regulating valves to ensure the required temperature conditions of the medium.

6. The intermediate microchannel reaction preparation apparatus according to claim 1, characterized in that: The first reagent is dichloromethane, the second reagent is diethylamine, and the third reagent is hexachloropropene.

7. The intermediate microchannel reaction preparation apparatus according to claim 1, characterized in that: The dosing pump (7) is a metering pump, electromagnetic pump, digital pump or hose pump, and the dosing pump (7) receives control signals through a frequency converter to realize automated dosing control.

8. The intermediate microchannel reaction preparation apparatus according to claim 1, characterized in that: The shell sides of the tubular reactor (15), static mixer (13), and each precooler (12) are all connected to a thermostat.

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