A continuous preparation device for Grignard reagent and its preparation method

Abstract

A continuous preparation device for Grignard reagent and its preparation method. The preparation device includes a reaction module, a feeding and discharging module, and a data acquisition and control module; the reaction module includes two reaction tubes and a transfer kettle; the two reaction tubes are respectively connected to the bottom of the transfer kettle through pipelines provided with solenoid valves, and the upper parts of the two reaction tubes are respectively connected to a nitrogen filling device and a vacuum pump through pipelines provided with solenoid valves; both reaction tubes are provided with circulating water jackets, and a punched mesh cylinder and a stirrer are arranged in the reaction chamber; the feeding module includes two liquid-phase raw material tanks and a solid-phase feeding tank; the data acquisition and control module includes thermocouples respectively arranged at the upper and lower parts of the two reaction tubes, a flowmeter arranged on the infusion pipeline, a mass meter arranged on the feeding pipeline, and a sample collection device arranged on the discharging pipeline. The present invention can realize the completely continuous preparation of Grignard reagent, with high production efficiency, good product quality and stable quality.

Description

Technical Field

[0001] The present invention relates to the technical field of Grignard reagent preparation devices and Grignard reagent preparation methods. Background Art

[0002] In 1901, the French chemist Victor Grignard first prepared a class of organometallic compounds containing magnesium halide, which the chemical community called "Grignard reagent", namely Grignard reagent. This reagent is commonly used in organic synthesis and is widely used in the fields of chemistry, chemical engineering, biopharmaceuticals, etc.

[0003] Currently, the batch method is mostly used for the preparation or production of Grignard reagent in China. This method uses a kettle reactor, in which magnesium, halogenated hydrocarbon, and solvent are mixed and then reacted. Its advantage is that the process is mature, and the remaining Grignard reagent after discharging can be used for the initiation of the next batch of reactions. However, it has an inherent drawback - the preparation process of Grignard reagent will generate a large amount of heat, which belongs to a dangerous chemical process; when using a kettle reactor, it involves process processes such as high temperature, low pressure, and rapid temperature change, so the requirements for the reactor are relatively harsh, and the production cost can only be reduced by pursuing economies of scale, that is, increasing the volume and quantity of reaction equipment; when the volume of the reactor increases, the instability of the process also increases more significantly, making the process control requirements more stringent. The contradiction among "economy" - "safety" - "stability" - "production scale" restricts the Grignard reagent industry, and thus inevitably affects the downstream. Therefore, changing the Grignard reagent preparation method and improving production efficiency have a very positive effect on the downstream industry level.

[0004] Carrying out continuous reaction based on a tubular reactor is a feasible way to improve production efficiency. This method is close to the ideal "plug flow", and has made great improvements in terms of safety, stability, and economy compared with the kettle reactor. However, for the Grignard reaction, since there is solid magnesium in the reactants, a traditional tubular reactor cannot be used. In order to achieve the continuity of the Grignard process, it is necessary to change the process idea and innovate and optimize the reactor.

[0005] Chinese patents CN102603775A and CN215694030U disclose reactors for continuously preparing Grignard reagent. However, the so-called continuity therein is only the continuity of one reaction cycle, and the complete continuity of the process has not been truly achieved. CN114950309A, etc. also mention the continuous preparation of Grignard reagent. However, the above-mentioned patents all focus on the temperature control link, and do not mention the most core and essential problem - the participation of solid phase in the reaction. Summary of the Invention

[0006] Aiming at the problems and deficiencies existing in the prior art, the present invention provides a reaction device for continuously preparing Grignard reagent and a method for preparing Grignard reagent thereof to meet the requirements of product stability and process safety.

[0007] The technical solution adopted by the present invention is as follows:

[0008] A continuous preparation device for Grignard reagent, comprising a reaction module, a feeding and discharging module, and a data acquisition and control module;

[0009] The reaction module includes a first reaction tube, a second reaction tube, and a transfer kettle; the lower parts of the first reaction tube and the second reaction tube are respectively connected to the bottom of the transfer kettle through pipelines provided with solenoid valves, and the upper parts of the first reaction tube and the second reaction tube are respectively connected to a nitrogen filling device and a vacuum pump through pipelines provided with solenoid valves; both the first reaction tube and the second reaction tube are reaction tubes provided with a circulating water jacket, and the inner cavity of the reaction tube is a material reaction cavity; the inner wall of the reaction cavity is provided with a punched mesh cylinder, and a stirrer is also provided in the reaction cavity;

[0010] The feeding module includes a first liquid-phase raw material tank, a second liquid-phase raw material tank, and a solid-phase feeding tank, a first infusion pump and its infusion pipeline for transporting the liquid-phase material in the first liquid-phase raw material tank to the first reaction tube and the second reaction tube, a second infusion pump and its infusion pipeline for transporting the liquid-phase material in the second liquid-phase raw material tank to the first reaction tube and the second reaction tube, a feeding pipeline for transporting the solid-phase material in the solid-phase feeding tank to the first reaction tube and the second reaction tube, and a discharging pipeline for discharging the reaction materials in the first reaction tube and the second reaction tube; solenoid valves are arranged on the infusion pipeline, the feeding pipeline, and the discharging pipeline, and a sample collection port is arranged on the discharging pipeline;

[0011] The data acquisition and control module includes thermocouples respectively arranged at the upper and lower parts of the first reaction tube and the second reaction tube, a flow meter arranged on the infusion pipeline, a mass meter arranged on the feeding pipeline, and a sample collection device arranged at the sample collection port on the discharging pipeline;

[0012] The solenoid valves, thermocouples, flow meters, mass meters, and sample collection devices are all connected to the control system in the computer.

[0013] Preferably, the mesh size of the punched mesh cylinder in the first reaction tube and the second reaction tube is 5-60 meshes.

[0014] Preferably, the stirrer includes a stirring shaft with stirring paddles penetrating through the reaction tube, and the top of the stirring shaft extends outside the reaction tube and is connected to a stirring motor.

[0015] Preferably, the thermocouples are respectively arranged in the circulating water jacket covering areas of the first reaction tube and the second reaction tube, and are respectively arranged at a position higher than the water inlet of the lower part of the circulating water jacket and at a position at the same height as the water outlet of the upper part.

[0016] The method for preparing Grignard reagent using the above continuous preparation device for Grignard reagent is as follows:

[0017] A. Reaction preparation stage: Open the solenoid valve on the feed pipeline, and put the magnesium flakes in the solid-phase feed tank into the interlayer between the punching net cylinder and the pipe wall in the two first reaction tubes and the second reaction tube respectively through the feed pipeline by gravity. The feeding amount accounts for 50% - 80% of the interlayer capacity; Load the solvent into the first liquid-phase raw material tank and the halogenated hydrocarbon into the second liquid-phase raw material tank; Turn on the vacuum pump and evacuate the first reaction tube, the second reaction tube and the transfer kettle to P / P0 < 0.2; Then close all pipelines by controlling the solenoid valve;

[0018] B. Reaction start-up stage: Open the solenoid valve, the first infusion pump and the second infusion pump on the infusion pipeline, inject the solvent and the halogenated hydrocarbon into the first reaction tube and the second reaction tube respectively according to the mass ratio of (2 - 5.5):1, and start the stirrer; After the liquid-phase materials are injected, close the infusion pipeline, inject the circulating water at 75 - 85 °C into the circulating water jackets of the first reaction tube and the second reaction tube to heat the liquid-phase materials in the reaction cavity, start the liquid-phase reaction, and a large amount of heat is released after the reaction is initiated. At this time, inject the circulating water at 35 - 65 °C into the circulating water jacket and control the temperature stability by controlling the cooling water flow. After the temperature change is gentle, it is regarded as the completion of the start-up stage. At this time, the Grignard reagent has been generated in the first reaction tube and the second reaction tube; Then inject the circulating water at 65 - 75 °C into the circulating water jacket to maintain the temperature;

[0019] C. Continuous reaction stage: In the first stage, open the liquid inlet pipeline connected to the first reaction tube, inject the solvent and halogenated hydrocarbon into the first reaction tube. At this time, the Grignard reagent in the first reaction tube flows out through the discharge pipe connected to the outlet of the first reaction tube to obtain the product, and the unflowed Grignard reagent becomes the initiator. Under the reaction temperature range of 65 - 75 °C and the action of the initiator, start the stirrer at the same time. The solvent and halogenated hydrocarbon injected into the first reaction tube continuously react with the magnesium in the tube to form the Grignard reagent, realizing the continuous reaction in the first stage. In the second stage, close the liquid inlet pipeline of the first reaction tube, and at the same time open the liquid inlet pipeline of the second reaction tube, inject the solvent and halogenated hydrocarbon into the second reaction tube. At this time, the Grignard reagent in the second reaction tube flows out through the discharge pipe connected to the outlet of the second reaction tube to obtain the product, and the unflowed Grignard reagent becomes the initiator. Under the reaction temperature range of 65 - 75 °C and the action of the initiator, start the stirrer at the same time. The solvent and halogenated hydrocarbon injected into the second reaction tube continuously react with the magnesium in the tube to form the Grignard reagent, realizing the continuous reaction in the second stage. During the continuous reaction in the second stage, close the stirrer in the first reaction tube, open the pipeline connecting the nitrogen charging and discharging device and the first reaction tube, and the pipeline connecting the intermediate reactor and the first reaction tube, inject nitrogen, and press the Grignard reagent in the first reaction tube into the intermediate reactor; then close the nitrogen charging device, the pipeline connecting the nitrogen charging and discharging device and the first reaction tube, and the pipeline connecting the intermediate reactor and the first reaction tube, open the feed pipeline connecting the solid-phase feeding tank and the first reaction tube, put the magnesium pieces into the first reaction tube, and perform magnesium filling on the first reaction tube; after the filling is completed, close the solid-phase feeding pipeline, open the vacuum pump, evacuate the first reaction tube to P / P0 < 0.2; close the vacuum pump, open the nitrogen charging device, open the pipeline between the intermediate reactor and the first reaction tube, press the Grignard reagent in the intermediate reactor back into the first reaction tube, and close the pipeline after completion; In the third stage, use the first reaction tube to repeat the continuous reaction in the first stage, and at the same time perform magnesium filling on the second reaction tube; through the alternating continuous reactions in the second and third stages, the complete continuous preparation of the Grignard reagent is realized.

[0020] Preferably, in the above step B, the stirring rate of the stirrer is 10 - 320 rad / min, and more preferably 60 - 120 rad / min.

[0021] Preferably, the equivalent diameter of the magnesium piece particles is 10 - 20 mm.

[0022] The present invention realizes the continuous Grignard reaction in the true sense and improves the preparation efficiency of the Grignard reagent. Through the continuous process, the process deviation in different batches is avoided, and the product quality stability is improved. By replacing the traditional batch reactor, the process hazard is greatly reduced, and the requirements for equipment are not harsh. Description of the Drawings

[0023] Figure 1It is a structural schematic diagram of the continuous preparation device of the Grignard reagent of the present invention;

[0024] Figure 2 It is a schematic diagram of the perforated mesh tube and the agitator arranged in the first reaction tube. Implementation

[0025] The present invention is further described in detail below with reference to the accompanying drawings and embodiments.

[0026] like Figure 1 As shown, the continuous preparation device of Grignard reagent provided by the present invention comprises a reaction module, a material input and output module and a data acquisition and control module;

[0027] The reaction module includes a first reaction tube 101, a second reaction tube 102 and a transfer kettle 103; the lower parts of the first reaction tube and the second reaction tube are connected to the bottom of the transfer kettle through pipelines provided with solenoid valves, and the upper parts of the first reaction tube and the second reaction tube are connected to a nitrogen charging device 104 and a vacuum pump 105 through pipelines provided with solenoid valves. The first reaction tube and the second reaction tube are both reaction tubes provided with circulating water jackets, and the inner cavity of the reaction tube is a material reaction chamber. Figure 2 As shown, a perforated mesh tube 1011 is provided in the material reaction chamber, and the mesh size of the perforated mesh tube is 5-60 mesh, and can be further preferably 10-30 mesh. A stirrer is provided in the reaction chamber. The stirrer is a prior art device, including a stirring shaft 1012 with a stirring paddle 1013, and the top end of the stirring shaft extends outside the reaction tube and is connected to a stirring motor. The stirrers in the first reaction tube and the second reaction tube are arranged in the same manner.

[0028] The feeding module includes a first liquid raw material tank 201, a second liquid raw material tank 202, and a solid-phase feeding tank 205, a first infusion pump 203 and an infusion pipeline for conveying liquid materials in the first liquid raw material tank to the first reaction tube and the second reaction tube, a second infusion pump 204 and an infusion pipeline for conveying liquid materials in the second liquid raw material tank to the first reaction tube and the second reaction tube, a feeding pipeline for conveying solid materials in the solid-phase feeding tank to the first reaction tube and the second reaction tube, and a discharge pipeline for outputting the reaction materials in the first reaction tube and the second reaction tube; solenoid valves are arranged on the infusion pipeline, the feeding pipeline, and the discharge pipeline, and a sample collection port is arranged on the discharge pipeline.

[0029] The data acquisition and control module includes thermocouples respectively arranged at the upper and lower parts of the first reaction tube and the second reaction tube, a flow meter arranged on the infusion pipeline, a mass meter arranged on the feed pipeline, and a sample collection device arranged at the sample collection port on the discharge pipeline. The thermocouples are respectively arranged in the covering area of the circulating water jacket of the first reaction tube and the second reaction tube, respectively arranged at a position higher than the water inlet of the lower part of the circulating water jacket and at the same height as the water outlet of the upper part.

[0030] The solenoid valve, thermocouple, flowmeter, mass meter, and sample collection device are all connected to the control system in the computer.

[0031] Specifically, as Figure 1 shown, the lower part of the first reaction tube 101 is connected to the lower end of the transfer kettle 103 and is controlled by the first solenoid valve 111; the upper part of the first reaction tube is connected to the nitrogen filling device 104 and is controlled by the second solenoid valve 112; the upper end of the first reaction tube is connected to the vacuum pump 105 and is controlled by the third solenoid valve 113. The low-temperature circulating water pipeline, high-temperature circulating water pipeline, and constant-temperature circulating water pipeline provided with solenoid valves are connected to the lower water inlet of the circulating water jacket 121 of the first reaction tube through a four-way valve. The lower part of the second reaction tube 102 is connected to the lower end of the transfer kettle 103 and is controlled by the fourth solenoid valve 114; the upper part of the second reaction tube is connected to the nitrogen charging and discharging device 104 and is controlled by the fifth solenoid valve 115; the upper end of the second reaction tube is connected to the vacuum pump 105 and is controlled by the sixth solenoid valve 116; the low-temperature circulating water pipeline, high-temperature circulating water pipeline, and constant-temperature circulating water pipeline provided with solenoid valves are connected to the lower water inlet of the circulating water jacket 122 of the second reaction tube through a four-way valve. The first thermocouple 301 is arranged at the lower part of the first reaction tube, higher than the water inlet of the circulating water jacket, and the second thermocouple 302 is arranged at the upper part of the first reaction tube, at the same height as the water outlet of the circulating water jacket. The third thermocouple 303 is arranged at the lower part of the second reaction tube, higher than the water inlet of the circulating water jacket, and the fourth thermocouple 304 is arranged at the upper part of the second reaction tube, at the same height as the water outlet of the circulating water jacket. The upper end of the transfer kettle 103 is respectively connected to the nitrogen filling device 104 and the vacuum pump 105 and is respectively controlled by the seventh solenoid valve 117 and the eighth solenoid valve 118.

[0032] The first liquid-phase raw material tank 201 and the first infusion pump 203 are connected by a pipeline and then divided into two paths through a three-way valve. One path is connected to the lower part of the first reaction tube 101 and a ninth solenoid valve 211 and a first flowmeter 311 are arranged on the pipeline; the other path is connected to the lower part of the second reaction tube 102 and a tenth solenoid valve 212 and a second flowmeter 312 are arranged on the pipeline. The second liquid-phase raw material tank 202 and the second infusion pump 243 are connected by a pipeline and then divided into two paths through a three-way valve. One path is connected to the lower part of the first reaction tube 101 and an eleventh solenoid valve 213 and a third flowmeter 313 are arranged on the pipeline; the other path is connected to the lower part of the second reaction tube 102 and a twelfth solenoid valve 214 and a fourth flowmeter 314 are arranged on the pipeline.

[0033] The discharge port of the solid-phase feeding tank 205 is divided into two paths. One path is connected to the upper part of the first reaction tube 101, and a thirteenth solenoid valve 215 and a first mass meter 315 are arranged on the pipeline; the other path is connected to the upper part of the second reaction tube 102, and a fourteenth solenoid valve 216 and a second mass meter 316 are arranged on the pipeline. The upper end of the first reaction tube 101 is connected to a discharge pipeline, and a first sample collection port 321 and a fifteenth solenoid valve 217 are arranged on the discharge pipeline; the upper end of the second reaction tube 101 is also connected to the discharge pipeline, and a second sample collection port 322 and a sixteenth solenoid valve 218 are arranged on the discharge pipeline.

[0034] The method for continuously preparing Grignard reagent using the above device is as follows:

[0035] A. Reaction preparation stage: Pour magnesium chips into the solid-phase feeding tank 205, open the thirteenth solenoid valve 215, the first mass meter 315, the fourteenth solenoid valve 216, and the second mass meter 316. Through the action of gravity, magnesium chips with an equivalent diameter of 10-20 mm are put into the mesh bags in the first reaction tube 101 and the second reaction tube 102. The first liquid-phase raw material tank 201 is filled with a solvent, and the second liquid-phase raw material tank 202 is filled with a halogenated hydrocarbon. Open the eighth solenoid valve 118, the third solenoid valve 113, and the sixth solenoid valve 116, turn on the vacuum pump 105, evacuate the first reaction tube 101, the second reaction tube 102, and the transfer kettle 103 to P / P0 < 0.2 (P0 refers to the pressure in the pipeline before evacuation; p refers to the pressure in the pipeline after evacuation), and then close the eighth solenoid valve 118, the third solenoid valve 113, the sixth solenoid valve 116, and the vacuum pump 105.

[0036] B. During the reaction startup stage, turn on the first infusion pump 203, the second infusion pump 204, as well as the ninth solenoid valve 211, the tenth solenoid valve 212, the eleventh solenoid valve 213, the twelfth solenoid valve 214, the fifteenth solenoid valve 217, and the sixteenth solenoid valve 218. Inject the solvent and the halogenated hydrocarbon into the first reaction tube and the second reaction tube in a ratio of (2 - 5.5):1. Start the stirrer. After the first reaction tube and the second reaction tube are filled, turn off the first infusion pump, the second infusion pump, and the ninth solenoid valve 211, the tenth solenoid valve 212, the eleventh solenoid valve 213, the twelfth solenoid valve 214, the fifteenth solenoid valve 217, and the sixteenth solenoid valve 218. Inject high-temperature circulating water at 75 - 85 °C into the circulating water jackets of the first reaction tube and the second reaction tube to heat the liquid-phase material in the reaction chamber and start the liquid-phase reaction. A large amount of heat will be released after the reaction is initiated. When the first thermocouple 301 and the third thermocouple 303 show a significant increase in temperature, inject low-temperature circulating water at 35 - 65 °C into the reaction tube circulating water jackets, and maintain the temperature stability by controlling the cooling water flow rate, and keep the reaction proceeding until the temperature change is gentle, that is, the temperature shown by the second thermocouple 302 and the fourth thermocouple 304 differs from the temperature of the injected circulating water by less than 2 degrees Celsius, which is regarded as the completion of the startup stage. At this time, the Grignard reagent has been generated in the first reaction tube and the second reaction tube. When the first thermocouple 301 and the third thermocouple 303 show a steady decrease in temperature, inject constant-temperature circulating water at 65 - 75 °C into the circulating water jackets to maintain the temperature;

[0037] C. Continuous reaction stage: In the first stage, turn on the first infusion pump 203, the second infusion pump 204, the ninth solenoid valve 211, the eleventh solenoid valve 213, and the fifteenth solenoid valve 217, and inject the solvent and the halogenated hydrocarbon into the first reaction tube 101 in proportion. At this time, the Grignard reagent in the first reaction tube is pumped out and flows out through the discharge pipe connected to the outlet of the first reaction tube to obtain the product. The unflowed Grignard reagent becomes the initiator. Under the action of the initiator in the reaction temperature range of 65 - 75 °C, turn on the stirrer at the same time. The newly injected solvent and halogenated hydrocarbon in the first reaction tube continuously carry out the Grignard reaction with the magnesium in the tube to generate the Grignard reagent, realizing the continuous reaction in the first stage. During the continuous reaction in the first stage, control the flow rate of the constant temperature circulating water to ensure that the temperature displayed by the second thermocouple 302 differs from the circulating water temperature by less than 2 degrees Celsius. In the second stage, close the ninth solenoid valve 211, the eleventh solenoid valve 213, and the fifteenth solenoid valve 217, and turn on the tenth solenoid valve 212, the twelfth solenoid valve 214, and the sixteenth solenoid valve 218. Inject the solvent and the halogenated hydrocarbon into the second reaction tube 102 in proportion. At this time, the Grignard reagent in the second reaction tube flows out through the discharge pipe connected to the outlet of the second reaction tube to obtain the product. The unflowed Grignard reagent becomes the initiator. Under the action of the initiator in the reaction temperature range of 65 - 75 °C, turn on the stirrer at the same time. The injected solvent and halogenated hydrocarbon in the second reaction tube continuously carry out the Grignard reaction with the magnesium in the tube to generate the Grignard reagent, realizing the continuous reaction in the second stage. During the continuous reaction in the second stage, control the flow rate of the constant temperature circulating water to ensure that the temperature displayed by the fourth thermocouple 304 differs from the circulating water temperature by less than 2 degrees Celsius. During the progress of the continuous reaction in the second stage, turn off the stirrer in the first reaction tube, turn on the nitrogen charging device 104, turn on the first solenoid valve 111 and the second solenoid valve 112, inject nitrogen, and press the Grignard reagent in the first reaction tube into the transfer kettle 103. Then turn off the nitrogen charging device 104, the first solenoid valve 111, and the second solenoid valve 112, turn on the thirteenth solenoid valve 215, put an appropriate amount of magnesium chips into the first reaction tube 101 and then turn off the thirteenth solenoid valve 215; turn on the vacuum pump 105 and the third solenoid valve 113, and evacuate the nitrogen in the first reaction tube 101 and then turn off the vacuum pump 105 and the third solenoid valve 113; turn on the nitrogen charging device 104, turn on the first solenoid valve 111 and the fifth solenoid valve 115, and press the Grignard reagent in the transfer kettle 103 back into the first reaction tube 101; then turn off the nitrogen charging device 104, the first solenoid valve 111, and the fifth solenoid valve 115, and turn on the stirrer in the first reaction tube. In the third stage, close the tenth solenoid valve 212, the twelfth solenoid valve 214, and the sixteenth solenoid valve 218, turn on the ninth solenoid valve 211, the eleventh solenoid valve 213, and the fifteenth solenoid valve 217, and then inject the solvent and the halogenated hydrocarbon into the first reaction tube 101 in proportion to carry out the continuous Grignard reaction, and control the flow rate of the constant temperature circulating water to ensure that the temperature displayed by the second thermocouple 302 differs from the circulating water temperature by less than 2 °C.During the continuous reaction in the third stage, turn off the stirrer of the second reaction tube, turn on the nitrogen charging device 104, turn on the fourth solenoid valve 114 and the fifth solenoid valve 115, and press the Grignard reagent in the second reaction tube 102 into the intermediate kettle 103; turn off the nitrogen charging device 104, the fourth solenoid valve 114 and the fifth solenoid valve 115, turn on the fourteenth solenoid valve 216, put an appropriate amount of magnesium chips into the second reaction tube 102 and then turn off the fourteenth solenoid valve 216; turn on the vacuum pump 105 and the sixth solenoid valve 116, evacuate the nitrogen in the second reaction tube 102 and then turn off the vacuum pump 105 and the sixth solenoid valve 116; turn on the nitrogen charging device 104, turn on the second solenoid valve 112 and the sixth solenoid valve 116, and press the Grignard reagent in the intermediate kettle 103 back into the second reaction tube 102. Then turn off the nitrogen charging device 104, the second solenoid valve 112 and the sixth solenoid valve 116, and turn on the stirrer in the second reaction tube. Through the alternating continuous reaction in the second and third stages, the complete continuous preparation of the Grignard reagent is realized. During the above continuous preparation of the Grignard reagent, the stirring rate of the stirrer is controlled to be 10 - 320 rad / min, preferably 60 - 120 rad / min.

[0038] During the continuous preparation of the Grignard reagent, when the Grignard reagent generated by the first reaction tube and the second reaction tube is discharged through the discharge pipeline, the sample collection device can regularly collect the Grignard reagent sample. By detecting its main component content and transmitting the detection information back to the computer, it is detected whether the Grignard reagent product is qualified.

[0039] Example 1 of continuous preparation of Grignard reagent: The first reaction tube and the second reaction tube used are made of stainless steel, with a height of 1.2 m, an inner diameter of the reaction tube of 80 mm, and a single-tube liquid holding capacity (i.e., the reaction chamber volume) of about 3.6 L.

[0040] In the reaction preparation stage, 500 g of magnesium chips with an equivalent diameter of 20 mm are added to the wire meshes of the first reaction tube and the second reaction tube respectively. Diethyl ether is filled in the first liquid-phase raw material tank as the solvent, and chlorobutane is filled in the second liquid-phase raw material tank as the reactant. The first reaction tube, the second reaction tube and the intermediate kettle are evacuated to P / P0 < 0.2;

[0041] In the reaction initiation stage, dibutyl ether and chlorobutane are respectively injected into the first reaction tube and the second reaction tube at a material injection rate of 11 mL / min of dibutyl ether and 2 mL / min of chlorobutane. The stirrers in the reaction tubes are started, and when the two reaction tubes are filled, the feeding is stopped. High-temperature circulating water at 82 °C is respectively injected into the circulating water jackets of the first reaction tube and the second reaction tube to heat the liquid-phase materials in the reaction chamber, and the liquid-phase reaction starts. After about 25 minutes, the temperature in the reaction tubes rises significantly. At this time, low-temperature circulating water at 45 °C is injected into the circulating water jackets of the first reaction tube and the second reaction tube to maintain the temperature stability. After about 5 minutes, the temperature in the reaction tubes drops back to 78 °C. At this time, constant-temperature circulating water at 75 °C is injected into the circulating water jackets of the first reaction tube and the second reaction tube to maintain the temperature stability, and the reaction continues for 4 hours.

[0042] In the continuous reaction stage, in the first stage, dibutyl ether and chlorobutane are injected into the first reaction tube at a rate of 11 mL / min and 2 mL / min respectively for continuous Grignard reaction. The temperature fluctuates between 78 and 79 °C, and the reaction duration is 4 hours. In the second stage, dibutyl ether and chlorobutane are injected into the second reaction tube at a rate of 11 mL / min and 2 mL / min respectively for continuous Grignard reaction. The temperature fluctuates between 78 and 79 °C, and the reaction duration is 4 hours. While the reaction in the second stage is proceeding, the feeding of the first reaction tube is paused, the stirrer in the first reaction tube is turned off, nitrogen is introduced into the first reaction tube, and the Grignard reagent generated in the first reaction tube is pressed into the transfer kettle. Then, 350 g of magnesium flakes are added to the mesh bag in the first reaction tube. After evacuating the first reaction tube, the Grignard reagent in the transfer kettle is pressed back into the first reaction tube, the stirrer and the discharge port are opened, and the Grignard reaction and the outflow of the Grignard reagent continue. In the third stage, the feeding of the second reaction tube is paused, the stirrer in the second reaction tube is turned off, nitrogen is introduced into the second reaction tube, and the Grignard reagent generated in the second reaction tube is pressed into the transfer kettle. Then, magnesium flakes are added to the mesh bag in the second reaction tube. After evacuating the second reaction tube, the Grignard reagent in the transfer kettle is pressed back into the second reaction tube, the stirrer and the discharge port are opened, and the Grignard reaction and the outflow of the Grignard reagent continue. Through the alternating operations in the above second stage and third stage, the complete continuous preparation of the Grignard reagent is realized.

[0043] Example 2 of the continuous preparation of the Grignard reagent: The first reaction tube and the second reaction tube used are made of stainless steel, with a height of 1.2 m, an inner diameter of 80 mm for the reaction tube, and a single-tube liquid holding capacity of about 3.6 L.

[0044] In the reaction preparation stage, 800 g of magnesium flakes with a diameter of 10 mm are added to the wire meshes of the first reaction tube and the second reaction tube respectively. Tetrahydrofuran is loaded into the first liquid-phase raw material tank as a solvent, and bromobenzene is loaded into the second liquid-phase raw material tank as a reactant. The first reaction tube, the second reaction tube and the transfer kettle are evacuated to P / P0 < 0.2;

[0045] In the reaction start-up stage, tetrahydrofuran and bromobenzene are injected into the first reaction tube and the second reaction tube respectively at a rate of 10 mL / min for tetrahydrofuran and 5 mL / min for bromobenzene. The stirrers in the reaction tubes are started. When the two reaction tubes are filled, the feeding is stopped. High-temperature circulating water at 76 °C is injected into the circulating water jackets of the first reaction tube and the second reaction tube respectively to heat the liquid-phase materials in the reaction chamber and start the liquid-phase reaction. After about 15 minutes, the temperature in the reaction tube rises significantly. At this time, low-temperature circulating water at 40 °C is injected into the circulating water jackets of the first reaction tube and the second reaction tube to maintain the temperature stability. After about 5 minutes, the temperature in the reaction tube drops back to 65 °C. At this time, constant-temperature circulating water at 65 °C is injected into the circulating water jackets of the first reaction tube and the second reaction tube to maintain the temperature stability, and the reaction continues for 6 hours.

[0046] In the continuous reaction stage, in the first stage, tetrahydrofuran and bromobenzene are injected into the first reaction tube at a rate of 10 mL / min and 5 mL / min respectively for continuous Grignard reaction. The temperature fluctuates between 65 and 66 °C, and the reaction time is 5 hours. In the second stage, hydrogen furan and bromobenzene are injected into the second reaction tube at a rate of 10 mL / min and 5 mL / min respectively for continuous Grignard reaction. The temperature fluctuates between 65 and 66 °C, and the reaction time is 5 hours. While the reaction in the second stage is in progress, the feeding of the first reaction tube is paused, the stirrer in the first reaction tube is turned off, nitrogen is introduced into the first reaction tube, and the Grignard reagent generated in the first reaction tube is pressed into the transfer kettle. Then, 450 g of magnesium flakes are added to the wire mesh in the first reaction tube. After evacuating the first reaction tube, the Grignard reagent in the transfer kettle is pressed back into the first reaction tube, and the stirrer is started to continue the reaction. In the third stage, the feeding of the second reaction tube is paused, the stirrer in the second reaction tube is turned off, nitrogen is introduced into the second reaction tube, and the Grignard reagent generated in the second reaction tube is pressed into the transfer kettle. Then, 450 g of magnesium flakes are added to the wire mesh in the second reaction tube. After evacuating the second reaction tube, the Grignard reagent in the transfer kettle is pressed back into the second reaction tube, and the stirrer is started to continue the reaction. Through the alternating operations of the above second stage and third stage, the complete continuous preparation of the Grignard reagent is achieved.

[0047] It should be noted that the above content is only used to further elaborate the technical solution of the present invention and should not be construed as a limitation on the protection scope of the present invention. Non-essential improvements made by those skilled in the art based on the above content of the present invention fall within the protection scope of the present invention.

Claims

1. A continuous preparation device for Grignard reagent, characterized in that, Including reaction module, material inlet and outlet module and data acquisition and control module; The reaction module comprises a first reaction tube (101), a second reaction tube (102) and a transfer kettle (103); the lower parts of the first reaction tube and the second reaction tube are connected to the bottom of the transfer kettle through pipelines provided with solenoid valves, and the upper parts of the first reaction tube and the second reaction tube are connected to a nitrogen charging device (104) and a vacuum pump (105) through pipelines provided with solenoid valves; the first reaction tube and the second reaction tube are both reaction tubes provided with circulating water jackets, and the inner cavity of the reaction tube is a material reaction chamber; a perforated mesh cylinder is provided in the reaction chamber, and a stirrer is also provided in the reaction chamber; The material inlet and outlet module comprises a first liquid raw material tank (201), a second liquid raw material tank (202), a solid-phase feeding tank (205), a first infusion pump (203) and a feeding pipeline thereof for conveying liquid materials in the first liquid raw material tank to the first reaction tube and the second reaction tube, a second infusion pump (204) and a feeding pipeline thereof for conveying liquid materials in the second liquid raw material tank to the first reaction tube and the second reaction tube, a feeding pipeline for conveying solid materials in the solid-phase feeding tank to the first reaction tube and the second reaction tube, and a discharging pipeline for discharging reaction materials in the first reaction tube and the second reaction tube; solenoid valves are arranged on the infusion pipeline, the feeding pipeline and the discharging pipeline, and a sample collection port is arranged on the discharging pipeline; The first liquid phase raw material tank and the first infusion pump are connected by a pipeline and then divided into two paths through a three-way valve, one path is connected to the lower part of the first reaction tube, and the other path is connected to the lower part of the second reaction tube; the second liquid phase raw material tank and the second infusion pump are connected by a pipeline and then divided into two paths through a three-way valve, one path is connected to the lower part of the first reaction tube, and the other path is connected to the lower part of the second reaction tube; The data acquisition and control module includes thermocouples respectively arranged at the upper and lower parts of the first reaction tube and the second reaction tube, a flow meter arranged on the infusion pipeline, a mass meter arranged on the solid phase feed pipeline, and a sample collection device arranged on the discharge pipeline; The solenoid valve, thermocouple, flow meter, mass meter and sample collection device are all connected to the control system in the computer.

2. The continuous preparation device of Grignard reagent according to claim 1, characterized in that, The mesh size of the perforated mesh tubes in the first reaction tube and the second reaction tube is 5-60 mesh.

3. The continuous preparation device for Grignard reagent according to claim 1 or 2, characterized in that, The stirrer comprises a stirring shaft with a stirring paddle penetrating the reaction tube, and the top end of the stirring shaft extends outside the reaction tube and is connected to a stirring motor.

4. A continuous preparation device for Grignard reagent according to claim 1 or 2, characterized in that, The thermocouples are respectively arranged in the circulation water jacket covering area of the first reaction tube and the second reaction tube, and are respectively arranged at a position higher than the water inlet of the lower part of the circulation water jacket and at a position at the same height as the water outlet of the upper part.

5. A method for continuously preparing a Grignard reagent using the continuous preparation device for Grignard reagent according to any one of claims 1-4, characterized in that, Here’s how: A. Reaction preparation stage: open the solenoid valve on the feed pipeline, and feed the magnesium flakes in the solid-phase feed tank into the interlayer between the perforated mesh tube and the tube wall in the first reaction tube and the second reaction tube through the feed pipeline by gravity, with the feed amount accounting for 50% to 80% of the interlayer capacity; load the solvent into the first liquid-phase raw material tank, and load the halogenated hydrocarbon into the second liquid-phase raw material tank; start the vacuum pump, and evacuate the first reaction tube, the second reaction tube and the transfer kettle to P / P0<0.2; then close all pipelines by controlling the solenoid valve; B. Reaction startup stage: Open the solenoid valve, the first infusion pump, and the second infusion pump on the infusion pipeline. Inject the solvent and the halogenated hydrocarbon into the first reaction tube and the second reaction tube respectively according to the mass ratio of (2 - 5.5):1, and start the stirrer. After the liquid-phase materials are injected, close the infusion pipeline. Inject circulating water at 75 - 85 °C into the circulating water jackets of the first reaction tube and the second reaction tube to heat the liquid-phase materials in the reaction chamber and start the liquid-phase reaction. A large amount of heat is released after the reaction is initiated. At this time, inject circulating water at 35 - 65 °C into the circulating water jacket and control the temperature stability by controlling the cooling water flow rate. After the temperature change becomes gentle, it is regarded as the completion of the startup stage. At this time, Grignard reagent has been generated in the first reaction tube and the second reaction tube. Then inject circulating water at 65 - 75 °C into the circulating water jacket to maintain the temperature; C. Continuous reaction stage: First stage, open the liquid inlet pipeline connected to the first reaction tube, and inject the solvent and the halogenated hydrocarbon into the first reaction tube. At this time, the Grignard reagent in the first reaction tube flows out through the discharge pipe connected to the outlet of the first reaction tube, and the Grignard reagent that does not flow out becomes the initiator. Under the reaction temperature range of 68 - 75 °C and the action of the initiator, start the stirrer at the same time. The solvent and the halogenated hydrocarbon injected into the first reaction tube continuously react with the magnesium in the tube to generate Grignard reagent, realizing the continuous reaction in the first stage; Second stage, close the liquid inlet pipeline of the first reaction tube, and at the same time open the liquid inlet pipeline of the second reaction tube, and inject the solvent and the halogenated hydrocarbon into the second reaction tube. At this time, the Grignard reagent in the second reaction tube flows out through the discharge pipe connected to the outlet of the second reaction tube, and the Grignard reagent that does not flow out becomes the initiator. Under the reaction temperature range of 68 - 75 °C and the action of the initiator, start the stirrer at the same time. The solvent and the halogenated hydrocarbon injected into the second reaction tube continuously react with the magnesium in the tube to generate Grignard reagent, realizing the continuous reaction in the second stage; During the continuous reaction in the second stage, close the stirrer in the first reaction tube, open the pipeline connecting the nitrogen charging device and the first reaction tube, and the pipeline connecting the intermediate reactor and the first reaction tube, inject nitrogen, and press the Grignard reagent in the first reaction tube into the intermediate reactor; Then close the nitrogen charging device, the pipeline connecting the nitrogen charging device and the first reaction tube, and the pipeline connecting the intermediate reactor and the first reaction tube. Open the feeding pipeline connecting the solid-phase feeding tank and the first reaction tube, and put magnesium flakes into the first reaction tube to fill the first reaction tube with magnesium; After the filling is completed, close the solid-phase feeding pipeline, open the vacuum pump, and evacuate the first reaction tube to P / P0 < 0.2; Close the vacuum pump, open the nitrogen charging device, open the pipeline between the intermediate reactor and the first reaction tube, and press the Grignard reagent in the intermediate reactor back into the first reaction tube. After completion, close the pipeline; Third stage, repeat the continuous reaction in the first stage using the first reaction tube, and at the same time fill the second reaction tube with magnesium; Through the alternating continuous reactions in the second stage and the third stage, the complete continuous preparation of Grignard reagent is realized.

6. The method for preparing Grignard reagent according to claim 5, wherein, In the above step B, the stirring rate of the stirrer is 10 - 320 rad / min.

7. The method for preparing Grignard reagent according to claim 6, wherein The stirring rate of the stirrer is 60 - 120 rad / min.

8. The method for preparing Grignard reagent according to claim 5 or 6, characterized in that, The equivalent diameter of the magnesium sheet particles is 10 - 20 mm.

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