Tubular reactor capable of continuously producing Grignard reagent

Abstract

The invention relates to the technical field of chemical synthesis, in particular to a tubular reactor capable of continuously producing Grignard reagents, which comprises an initiator, a Grignard reaction elbow, a discharge elbow and a discharge valve which are connected in sequence. The initiator comprises a feeding hole, a feeding pump, a gas guide pipe, an inert gas valve and a feeding pipe, and is used for injecting and mixing a halogenated hydrocarbon solution and an initiator; the Grignard reaction bent pipe comprises a material supplementing opening, a gas guide pipe and an inert gas valve and is used as a Grignard reaction area; the discharging bent pipe can prevent metal magnesium in the Grignard reactor from overflowing, and meanwhile, the discharging bent pipe is connected with a downstream reactor or Grignard reagent split charging equipment through the discharging valve, so that the generated Grignard reagent is discharged out of the tubular reactor. The tubular reactor has the beneficial effects that by using the tubular reactor provided by the invention, the Grignard reagent can be continuously produced in a mode of supplementing metal magnesium on line, the Grignard reaction risk is reduced, and the production process flow of the Grignard reagent is simplified.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular to a tubular reactor capable of continuously producing Grignard reagents. Background Art

[0002] As an important class of chemical reagents, Grignard reagents play an important role in the fields of chemical synthesis and chemical production. Since the carbon atom connected to magnesium has a strong nucleophilic reaction ability, Grignard reagents can react with most organic substances with positive centers such as aldehydes, ketones and esters, and can also react with compounds with active hydrogen atoms such as H2O and alcohols (phenols) to undergo double decomposition reactions. Therefore, Grignard reagents require halogenated hydrocarbons and metallic magnesium to be produced and prepared in aprotic solvents such as ether and tetrahydrofuran. In the existing Grignard reagent preparation process, the reaction devices used are mostly intermittent reactors. In order to allow halogenated hydrocarbons to fully contact with metallic magnesium and prevent the accumulation of a large amount of reaction heat to cause solvent boiling, the reaction system needs to be quickly stirred when producing Grignard reagents. Therefore, there is a risk of metallic magnesium scratching the inner wall of the reactor when using an intermittent reactor for Grignard reaction. In order to effectively overcome the above-mentioned safety hazards, in the process of producing Grignard reagents, it is not only necessary to configure a large amount of safety control equipment for the relevant reactor, but also to increase the frequency of equipment maintenance, further increasing production costs.

[0003] Based on the above factors, Chinese Patent 2020215079178 provides a reaction device for continuously producing corresponding Grignard reagents using halogenated hydrocarbons as raw materials. The risk of scratching the reactor can be effectively reduced by using magnesium powder instead of flaky or fast magnesium to prepare Grignard reagents. However, the mixed feeding method adopted by the patent is likely to cause unstable feeding ratio of the reactor and uneven mixing of materials, which may reduce the reaction conversion rate. At the same time, the use of filtering sintered mesh is also likely to cause material accumulation in the reaction bed. Chinese Patent 2023215172452 proposes that Grignard reagents can be continuously produced by a multi-reactor method. The method provided greatly improves the conversion rate by increasing the reaction time of the material, but the multi-stage use of the reactor will increase the equipment production cost and safety control cost. In addition, the method still uses mechanical stirring to increase the mixing effect of solid and liquid materials, and cannot completely avoid the mechanical wear of the metal magnesium on the inner wall of the reactor.

[0004] Chinese Patent No. 105377858A provides a method for preparing Grignard reagent using a fluidized bed. The Grignard reaction is carried out by comprehensively utilizing the fluidization of magnesium metal in a reactor or a fluidized bed and the counter-gravity flow of a halide solution. Although the provided method can avoid the heat accumulation problem of a kettle reactor, the magnesium powder used in the reaction process is prone to oxidation reaction when it contacts the air. In addition, the wear of the inner wall of the reactor by the flow of magnesium metal cannot be avoided. Chinese Patent No. 112724164 provides a loop reactor for preparing Grignard reagent. The provided reactor requires magnesium metal to be made into a slurry in advance to increase the consumption rate of magnesium metal. Not only does it fail to eliminate the wear of magnesium metal on the feed pump and the inner wall of the reactor, but there is also a risk of clogging of the filter screen of the Grignard reagent outlet pipe.

[0005] Chinese patents 118527067A and 118527068A respectively disclose a tubular reactor composed of multiple reaction tubes. The provided reactor not only realizes the continuous production of Grignard reagent by alternately replenishing metal magnesium in the reaction tubes, but also has the advantages of easy temperature control and less auxiliary equipment. However, the process flow of replenishing metal magnesium in the reaction tube is relatively complicated and has high operational difficulty. Summary of the invention

[0006] In view of the above-mentioned shortcomings of the prior art, the present invention provides a tubular reactor that can continuously produce Grignard reagents to solve the problems of the prior art. The provided tubular reactor continuously produces Grignard reagents by online supplementation of metallic magnesium, and has great application potential in the preparation of various Grignard reagents and related chemical production fields.

[0007] To achieve the above object, the technical solution adopted by the present invention is:

[0008] Provided is a tubular reactor capable of continuously producing a Grignard reagent, comprising an initiator, a Grignard reaction elbow, a discharge elbow and a discharge valve which are connected in sequence.

[0009] Furthermore, the initiator of the present invention comprises a feed port, a feed pump, an air guide pipe, an inert gas valve and a feed transfer pipe, which are used for injecting the halogenated hydrocarbon solution and the initiator.

[0010] Furthermore, the Grignard reaction elbow of the present invention comprises two feed ports, two gas guide pipes and two inert gas valves, and is used as a Grignard reaction zone.

[0011] Furthermore, the discharge elbow of the present invention is connected to the Grignard reaction elbow at one end, and is connected to the downstream reactor or Grignard reagent dispensing equipment through a discharge valve at the other end, so as to discharge the generated Grignard reagent from the Grignard reactor.

[0012] Furthermore, the initiator, Grignard reaction elbow and discharge elbow of the present invention can be made of one or more of glass, quartz, stainless steel and enamel-lined metal; preferably glass and quartz; more preferably glass.

[0013] Furthermore, the initiator and the Grignard reaction elbow of the present invention are thermostatic tubular containers filled with metallic magnesium, which serve as the reaction zone for metallic magnesium and halogenated hydrocarbons; the thermostatic tubular container can provide the required high temperature, room temperature or low temperature environment for the Grignard reaction; the thermostatic method can be one or more of the thermostatic methods of a water bath, an oil bath or a thermal conductivity module; preferably, the thermostatic method is a water bath or an oil bath; and more preferably, the thermostatic method is an oil bath.

[0014] Furthermore, the initiator of the present invention has an appearance of one of cylindrical, prismatic, elliptical or spherical; preferably cylindrical and spherical; more preferably cylindrical.

[0015] Furthermore, the Grignard reaction elbow of the present invention has an appearance of one of U-shape, V-shape or arc-shape; preferably U-shape and V-shape; more preferably U-shape.

[0016] Furthermore, the initiator feed pump of the present invention is used to inject the halogenated hydrocarbon solution and the initiator solution into the initiator through the feed port.

[0017] Furthermore, the initiator inert gas valve of the present invention is connected to an external inert gas source and is used to provide inert gas protection for the initiator through an air duct.

[0018] Furthermore, the initiator material transfer pipe of the present invention is used to transfer the halogenated hydrocarbon solution or the mixed solution containing halogenated hydrocarbon and initiator in the initiator to the Grignard reaction elbow.

[0019] Furthermore, the feeding port of the Grignard reaction elbow of the present invention is used to load metallic magnesium into the initiator and the Grignard reaction elbow.

[0020] Furthermore, the inert gas valve for the Grignard reaction elbow of the present invention is connected to an external inert gas source, and provides inert gas protection for the Grignard reaction elbow through a gas guide pipe.

[0021] Furthermore, the discharge elbow of the present invention is in one of an inverted U-shape, an inverted V-shape or an inverted arc shape; preferably an inverted U-shape and an inverted V-shape; more preferably an inverted U-shape.

[0022] Furthermore, the discharge valve of the present invention is used to be connected to a downstream reactor or a Grignard reagent dispensing device.

[0023] Furthermore, the inert gas described in the present invention may be nitrogen or argon, preferably nitrogen.

[0024] The beneficial effect of the present invention is that: using the tubular reactor provided by the present invention, the Grignard reagent can be produced uninterruptedly by online supplementation of metallic magnesium, thereby reducing the risk of the Grignard reaction and simplifying the production process of the Grignard reagent. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solution of the present invention, the drawings required for use in the embodiments and application examples will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For relevant technical personnel, other drawings can be derived based on the present invention without paying creative work.

[0026] Figure 1 It is a structural schematic diagram of a tubular reactor capable of continuously producing Grignard reagent provided by the present invention;

[0027] Figure 1 Explanation of the reference numerals: 100: initiator; 101: feed port; 102: feed pump; 103: air duct; 104: inert gas valve; 105: feed pipe; 200: Grignard reaction elbow; 201 and 202: feed port; 203 and 204: air duct; 205 and 206: inert gas valve; 300: discharge elbow; 400: discharge valve. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by relevant technicians without creative work are within the scope of protection of the present invention.

[0029] In the description of the present invention, it should be noted that, unless otherwise clearly stipulated and limited, all valves with closing functions are in an open state; terms such as "connected", "connected" and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integrated connection; it can be directly connected, indirectly connected through an intermediate medium, or connected internally between two components; directional words such as "up", "down", "left", "right", "top", "bottom" and "end" are based on the drawings in the specification, and relevant technical personnel can understand the actual meaning of the above terms in the present invention according to the specific circumstances.

[0030] like Figure 1 A tubular reactor capable of continuously producing Grignard reagents is shown, comprising an initiator 100, a Grignard reaction elbow 200, a discharge elbow 300 and a discharge valve 400 connected in sequence.

[0031] The initiator 100 comprises a feed port 101 , a feed pump 102 , a gas pipe 103 , an inert gas valve 104 and a feed pipe 105 ; the Grignard reaction elbow 200 comprises feed ports 201 and 202 , gas pipes 203 and 204 and inert gas valves 205 and 206 .

[0032] The feed port 101 is used to receive the halogenated hydrocarbon solution or the initiator solution transferred from the feed pump 102, and inject the received halogenated hydrocarbon solution or the initiator solution into the initiator 100; the gas guide pipe 103 is connected to the external inert gas source through the inert gas valve 104, and is used to provide inert gas protection for the initiator 100; the left side of the material transfer pipe 105 is connected to the bottom of the initiator 100, and the right side is connected to the left arm of the Grignard reaction elbow 200, and is used to feed the halogenated hydrocarbon solution in the initiator 100 or the mixed solution composed of the initiator and the halogenated hydrocarbon solution into the Grignard reaction elbow 200.

[0033] The feed ports 201 and 202 are used to add metal magnesium to the Grignard reaction elbow 200 before the Grignard reaction starts or when the metal magnesium is consumed to a certain extent; the gas guide pipes 203 and 204 are connected to an external inert gas source through inert gas valves 205 and 206 to provide inert gas protection for the Grignard reaction elbow 200.

[0034] The discharge elbow 300 is connected to the right arm of the Grignard reaction elbow 200 on the left side and connected to the downstream reactor or Grignard reagent dispensing equipment through the discharge valve 400 at the end, and is used to discharge the generated Grignard reagent from the Grignard reactor, and also has the function of preventing the overflow of metallic magnesium in the Grignard reaction elbow 200.

[0035] When the tubular reactor is used to produce the Grignard reagent, the equipment is preferably started according to the following operation flow: 1) Open the inert gas valves 104, 205 and 206 to place the initiator 100 and the Grignard reaction elbow 200 in an inert gas protection state; open the discharge valve 400 to connect the discharge elbow 300 with the downstream reactor or the Grignard reagent dispensing equipment; 2) Under the protection of inert gas, open the feed ports 201 and 202, and fill the initiator 100 and the Grignard reaction tube 200 with metal magnesium, so that the top of the metal magnesium is close to but does not exceed the connecting ports of the gas guide pipes 203 and 204 on the side wall of the Grignard reaction tube 200; 3) injecting the solvent used for the Grignard reaction into the Grignard reaction elbow 200, so that the solvent surface is slightly higher than the connecting port between the material transfer pipe 105 and the Grignard reaction elbow 200; 4) Seal the feeding ports 201 and 202; 5) adjusting the initiator 100 and the Grignard reaction tube 200 to the temperature required for the Grignard reaction; 6) Injecting a suitable amount of initiator into the initiator 100 through the feed port 101; 7) Turn on the feed pump 102 and continuously inject the halogenated hydrocarbon solution into the initiator 100 through the feed port 101; 8) With the continuous injection of the halogenated hydrocarbon solution, the halogenated hydrocarbon and metallic magnesium will continue to undergo Grignard reaction in the initiator 100 and the Grignard reaction elbow 200 , and at the same time, the generated Grignard reagent is continuously discharged from the Grignard reaction elbow 200 through the discharge elbow 300 .

[0036] Furthermore, during the operation of the tubular reactor, when the metal magnesium in the Grignard reaction elbow 200 is consumed to a certain extent, the metal magnesium is preferably added to the Grignard reaction elbow 200 according to the following operation process: 1) Appropriately increase the inert gas flow rate of the inert gas valves 205 and 206; 2) Open the feed ports 201 and 202; 3) Under the protection of inert gas, adding metallic magnesium into the Grignard reaction tube 200; 4) Seal the feeding ports 201 and 202; 5) Restore the inert gas flow of the inert gas valves 205 and 206; 6) The tubular reactor 200 is repeatedly supplemented with metallic magnesium according to the above process, thereby achieving continuous production of the Grignard reagent. Example 1

[0037] like Figure 1 As shown, a tubular reactor for continuously producing Grignard reagents, the initiator 100 is a cylindrical glass container with a height of 15 cm, an inner diameter of 2 cm and a glass stopper; the feed port 101 and the gas duct 103 are respectively glass tubes with an inner diameter of 0.6 cm; the feed port 101 is connected to the halogenated hydrocarbon solution storage tank through the feed pump 102, and the gas duct 103 is connected to the external high-purity nitrogen source through the inert gas valve 104; the feed pipe 105 connected to the right side of the initiator 100 and the left arm of the Grignard reaction elbow 200 at a distance of 12 cm from the top of the initiator 100 is a glass tube with a length of 5 cm and an inner diameter of 2 cm.

[0038] like Figure 1 As shown, a tubular reactor for continuously producing Grignard reagents, wherein the Grignard reaction elbow 200 is a U-shaped glass tube with glass stoppers at both ends; the inner diameter of the U-shaped glass tube is 2 cm; the length of the straight tubes on both sides of the Grignard reaction elbow 200 is about 30 cm, and the bending radius of the arc-shaped tube at the bottom is about 10 cm; there is a glass gas guide tube (203 and 204) with an inner diameter of 0.6 cm at 5 cm from both ends of the Grignard reaction elbow 200; the gas guide tubes 203 and 204 are connected to an external high-purity nitrogen source through inert gas valves 205 and 206, respectively.

[0039] like Figure 1As shown, a tubular reactor for continuously producing Grignard reagent, the discharge elbow 300 is an inverted U-shaped glass tube with an inner diameter of 1.5 cm; the left end of the discharge elbow 300 is connected to the top 12 cm of the right arm of the Grignard reaction elbow 200; the end of the discharge elbow 300 is connected to the downstream reactor or Grignard reagent filling equipment through a discharge valve 400. Application Examples

[0040] The Grignard reactor described in Example 1 is used as a Grignard reagent production device to implement the following application examples. The general operation method of the Grignard reactor is as follows: First, all components are thoroughly dried and assembled into a Grignard reactor, the inert gas valves 104, 205 and 206 are opened to connect to an external high-purity nitrogen source to protect the initiator 100 and the Grignard reaction elbow 200 with inert gas, and the discharge valve 400 is opened to connect the discharge elbow 300 with the downstream reactor or the Grignard reagent dispensing equipment; then, the initiator 100 and the Grignard reaction elbow 200 are filled with metal magnesium and solvent through the feed ports 201 and 202; secondly, after a certain amount of initiator is injected into the initiator 100 through the feed port 101, the feed pump 102 is turned on to continuously inject the halogenated hydrocarbon solution into the initiator 100 through the feed port 101; in addition, during the operation of the reactor, metal magnesium is supplemented in time through the feed port 201 and into the Grignard reaction tube 200. The initiator concentration used is 0.8 mol / L, the initiator dosage is 10 ml; the injection rate of the halogenated hydrocarbon solution is 100 ml / hour. After the reaction is stable, three batches of 100 ml of Grignard reagent solution are continuously received to test the conversion rate of the Grignard reagent; the average conversion rate of the Grignard reagent and other operating parameters are shown in the specific application example: 1. Continuous production of aromatic hydrocarbon magnesium halide reagents:

[0041] Continuous production of phenylmagnesium bromide: bromobenzene concentration is 156 g / L, Grignard reaction tube temperature is set to 60 degrees, solvent is anhydrous 2-methyltetrahydrofuran, and the average conversion rate of Grignard reagent is not less than 85%.

[0042] Continuous production of 4-phenylphenyl magnesium chloride: 4-phenylchlorobenzene concentration is 189 g / L, Grignard reaction tube temperature is set to 50 degrees, solvent is anhydrous tetrahydrofuran, and the average conversion rate of Grignard reagent is not less than 87%.

[0043] Continuous production of 3-methylphenylmagnesium iodide: The concentration of 3-methyliodobenzene is 218 g / L, the temperature of the Grignard reaction tube is set to 25 degrees, the solvent is anhydrous tetrahydrofuran, and the average conversion rate of the Grignard reagent is not less than 84%. 2. Continuous production of aliphatic magnesium halide reagents:

[0044] Continuous production of ethylmagnesium bromide: the ethyl bromide concentration is 109 g / L, the temperature of the Grignard reaction tube is set to 40 degrees, the solvent is anhydrous tetrahydrofuran, and the average conversion rate of the Grignard reagent is not less than 92%.

[0045] Continuous production of benzyl magnesium chloride: the concentration of chloromethylbenzene is 127 g / L, the temperature of the Grignard reaction tube is set to 25 degrees, the solvent is anhydrous tetrahydrofuran, and the average conversion rate of the Grignard reagent is not less than 90%.

[0046] Continuous production of 1-butylmagnesium iodide: 1-iodobutane concentration is 184 g / L, Grignard reaction tube temperature is set to 5 degrees, solvent is anhydrous tetrahydrofuran, and the average conversion rate of Grignard reagent is not less than 80%. 3. Continuous production of cycloalkyl magnesium halide reagents:

[0047] Continuous production of cyclohexylmagnesium bromide: the concentration of bromocyclohexane is 163 g / L, the temperature of the Grignard reaction tube is set to 35 degrees, the solvent is anhydrous tetrahydrofuran, and the average conversion rate of the Grignard reagent is not less than 82%.

[0048] Continuous production of 2-cyclopentenylmagnesium chloride: the concentration of 3-chlorocyclopentene is 103 g / L, the temperature of the Grignard reaction tube is set to 25 degrees, the solvent is anhydrous tetrahydrofuran, and the average conversion rate of the Grignard reagent is not less than 84%.

[0049] Continuous production of 4-methyl-2-cyclohexylpropylmagnesium iodide: the concentration of 3-methyl-6-iodocyclohexene is 222 g / L, the temperature of the Grignard reaction tube is set at 20 degrees, the solvent is anhydrous tetrahydrofuran, and the average conversion rate of the Grignard reagent is not less than 80%.

[0050] Finally, it is to be noted that the description of the composition of the Grignard reaction system and the above application examples of the present invention have fully demonstrated that the tubular reactor provided by the present invention can be widely used for the continuous production of various Grignard reagents. Due to space limitations, the size, connection method and applicable Grignard reaction of the Grignard reactor involved in the present invention cannot be listed one by one, so the above embodiments and application examples are only used to illustrate the technical solution of the present invention, rather than to limit it; although the present invention is described in detail with reference to the above embodiments and application examples, relevant technical personnel should understand that it is still possible to modify the technical solutions recorded in the above embodiments, or to replace some of the technical features therein by equivalents; and these modifications or equivalent replacements do not make the essence of the corresponding technical solutions deviate from the spirit and protection scope of the present invention.

Claims

1. A tubular reactor capable of continuously producing a Grignard reagent, characterized in that: The invention comprises an initiator, a Grignard reaction elbow, a discharge elbow and a discharge valve which are connected in sequence.

2. The tubular reactor according to claim 1, characterized in that: The initiator is equipped with some or all accessories including a feed port, a feed pump, an air guide pipe, an inert gas valve and a feed pipe; preferably, all accessories are equipped.

3. The initiator according to claim 2, characterized in that: The initiator may have a cylindrical, prismatic, elliptical or spherical appearance; preferably cylindrical and spherical; more preferably cylindrical.

4. The tubular reactor according to claim 1, characterized in that: The Grignard reaction elbow is equipped with some or all accessories including a feed port, a gas guide pipe and an inert gas valve; preferably, all accessories are equipped.

5. The tubular reactor according to claim 1, characterized in that: The Grignard reaction elbow may have a U-shape, a V-shape or an arc shape; preferably a U-shape or a V-shape; more preferably a U-shape.

6. The Grignard reaction elbow according to claim 4, characterized in that: The required constant temperature environment can be provided for the Grignard reaction; the constant temperature method can be one or more of water bath constant temperature, oil bath constant temperature or thermal conductivity module constant temperature; preferably water bath constant temperature and oil bath constant temperature; more preferably oil bath constant temperature.

7. The tubular reactor according to claim 1, characterized in that: The appearance of the discharge elbow can be one of an inverted U-shape, an inverted V-shape or an inverted arc shape; preferably an inverted U-shape and an inverted V-shape; more preferably an inverted U-shape.

8. The tubular reactor according to claim 1, characterized in that: When the tubular reactor is used to produce the Grignard reagent, the equipment can be started in sequence through all or part of the following steps: 1) opening the inert gas valve to put the initiator and the Grignard reaction elbow in an inert gas protection state; opening the discharge valve to connect the discharge elbow with the downstream reactor or the Grignard reagent dispensing equipment; 2) under the inert gas protection state, opening the feed port to fill the initiator and the Grignard reaction tube with metal magnesium so that the top of the metal magnesium is close to but not higher than the opening of the gas guide tube on the side wall of the Grignard reaction elbow; 3) injecting the solvent used for the Grignard reaction into the Grignard reaction elbow so that the solvent surface The surface is slightly higher than the upper wall of the feed pipe; 4) the feed port is sealed; 5) the initiator and the Grignard reaction tube are adjusted to the temperature required for the Grignard reaction; 6) an appropriate amount of initiator is injected into the initiator through the feed port; 7) the feed pump is turned on, and the halogenated hydrocarbon solution is continuously injected into the initiator through the feed port; 8) as the halogenated hydrocarbon solution is continuously injected into the initiator, the halogenated hydrocarbon and metallic magnesium will continue to undergo Grignard reaction in the initiator and the Grignard reaction elbow, and the generated Grignard reagent is continuously discharged from the Grignard reaction elbow through the discharge elbow; preferably, the tubular reactor is started after all the above steps.

9. The tubular reactor according to claim 1, characterized in that: During the operation of the tubular reactor, magnesium metal can be added to the Grignard reaction elbow through all or part of the following steps in sequence: 1) appropriately increasing the inert gas flow rate of the inert gas valve; 2) opening the feed port; 3) adding magnesium metal to the Grignard reaction tube under the protection of the inert gas; 4) sealing the feed port; 5) restoring the inert gas flow rate of the inert gas valve; preferably, magnesium metal is added to the Grignard reaction elbow through all the above steps.

10. The tubular reactor according to claim 1, characterized in that The tubular reactor can be applied to, but not limited to, the production field of Grignard reagents using various halogenated hydrocarbons such as halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbons or halogenated cyclic hydrocarbons as raw materials or other related chemical production fields.

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