A continuous kettle production process for grignard reagent

Abstract

The application discloses a kind of continuous kettle type production Grignard reagent process.The application can increase product batch yield by at least one time or more using sequential series continuous stirred tank equipment, the overall feed molar ratio of raw material magnesium and allyl chloride is reduced to 1.2-1.8 times, the amount of raw material magnesium is greatly reduced, thereby greatly reducing the difficulty and time of post-processing, reducing operating cost, and saving raw material cost, reaction time is saved by more than 2 times, in addition, the application can not only obtain Grignard reagent with a concentration of 1.5-1.7 M, but also inhibit the occurrence of coupling side reactions, the concentration of coupling byproduct is not more than 5% at most, ensuring the effective concentration and yield of the final product.

Description

Technical Field

[0001] This invention relates to the field of Grignard reagent production, and more specifically to a continuous batch process for producing Grignard reagents. Background Technology

[0002] Organomagnetic reagents, also known as Grignard reagents, are formed by the reaction of haloalkanes with metallic magnesium in anhydrous diethyl ether or tetrahydrofuran. The general formula for Grignard reagents is R-Mg-X, where R is an aliphatic or aromatic hydrocarbon group and X is a halogen (Cl, Br, or I). They are extremely reactive and can react with compounds containing active hydrogen (such as H₂O, ROH, RC≡CH), aldehydes, ketones, esters, acyl halides, nitriles, ethylene oxide, haloalkanes, carbon dioxide, phosphorus trichloride, boron trichloride, silicon tetrachloride, etc., making them important reagents for organic synthesis.

[0003] Current technologies employ batch-process, autoclave-type production of Grignard reagents. For the synthesis of highly reactive allyl-position Grignard reagents, a significant excess of magnesium is required to suppress coupling side reactions. For example, in the production process of allyl magnesium chloride, the molar ratio of magnesium to allyl chloride must be at least 2.5 times to ensure a Grignard solution concentration of 1.0 to 1.5 M or higher. This not only significantly increases production costs but also requires a large amount of slurry-like solids to settle or filter during post-processing, increasing operational complexity and reducing production efficiency. Summary of the Invention

[0004] To address the problems existing in the prior art, the present invention provides a continuous batch process for producing Grignard reagents.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] A continuous batch process for producing Grignard reagents, comprising:

[0007] Magnesium and organic solvent were added to the first, second and third reactors connected in series, respectively, and the temperature of each reactor was controlled at -10 to 0℃ to replace the atmosphere with an inert atmosphere.

[0008] A mixture of halogenated hydrocarbons and organic solvents is continuously fed into the first reactor. When the concentration of alkyl magnesium halide in the first reactor reaches 1-1.2 M, the material from the first reactor overflows into the second reactor. When the concentration of alkyl magnesium halide in the second reactor reaches 1.35-1.5 M, the material from the second reactor overflows into the third reactor, yielding a Grignard reagent with a concentration of 1.5-1.7 M.

[0009] In one specific embodiment, the mass-to-volume ratio of raw material magnesium to organic solvent in the first reaction vessel is (85-100) kg: 50 L;

[0010] And / or, in the second reactor, the mass-to-volume ratio of raw material magnesium to organic solvent is (50-65) kg: 30 L;

[0011] And / or, in the third reaction vessel, the mass-to-volume ratio of raw material magnesium to organic solvent is (0.1-0.3) kg: 10 L;

[0012] And / or, the mass ratio of raw magnesium in the first reactor, the second reactor and the third reactor is (85-100):(50-65):(0.1-0.3).

[0013] In one specific embodiment, the concentration of the halohydrocarbon in the mixture of the halohydrocarbon and the organic solvent is 2.5-3M;

[0014] And / or, the total amount of magnesium used in the raw materials is in a molar ratio of 1.2-1.8:1 to the amount of haloalkanes.

[0015] In one specific embodiment, a mixture of halogenated hydrocarbons and organic solvents is continuously fed into the first reactor at a rate of 0.8-1.2 L / min. When the temperature of the first reactor reaches 8-12°C, the cooling water rate is adjusted to maintain the temperature of the first reactor at 8-12°C. After 20-40 min, the temperature of the first reactor is raised to 20-30°C. After 55-65 min, the mixture of halogenated hydrocarbons and organic solvents is continuously fed into the first reactor at a rate of 1.8-2.2 L / min. When the concentration of hydrocarbon-based magnesium halide in the first reactor reaches 1-1.2 M, the material from the first reactor is continuously overflowed into the second reactor at a rate of 1.8-2.2 L / min.

[0016] In one specific embodiment, the material from the first reactor overflows into the second reactor. When the temperature of the second reactor rises to 8-12°C, the cooling water rate is adjusted to maintain the temperature of the second reactor at 8-12°C. After 8-12 minutes, the temperature of the second reactor is raised to 20-30°C. When the concentration of hydrocarbon-based magnesium halide in the second reactor reaches 1.35-1.5M, the material from the second reactor is continuously overflowed into the third reactor at a rate of 1.8-2.2 L / min.

[0017] In one specific embodiment, the material from the second reactor overflows into the third reactor. When the temperature of the third reactor rises to 8-12°C, the cooling water rate is adjusted to maintain the temperature of the third reactor at 8-12°C. After 8-12 minutes, the temperature of the third reactor is raised to 20-30°C. When the concentration of hydrocarbon-based magnesium halide in the third reactor reaches 1.5-1.7M, the material is continuously discharged at a rate of 1.8-2.2L / min to obtain a Grignard reagent with a concentration of 1.5-1.7M.

[0018] In one specific embodiment, the haloalkane includes allyl chloride, allyl iodine, benzyl bromide, benzyl chloride, or benzyl iodide.

[0019] In one specific embodiment, the organic solvent is an ether solvent, or a mixture of an ether solvent and toluene. The ether solvent is a common ether solvent used in the preparation of Grignard reagents, such as tetrahydrofuran or diethyl ether.

[0020] The present invention has the following advantages:

[0021] This invention employs a sequentially connected continuous stirred tank reactor, which can increase the batch production of products by at least 100%. The overall molar ratio of raw material magnesium to allyl chloride is reduced to 1.2-1.8 times, significantly reducing the amount of raw material magnesium used. This greatly reduces the difficulty and time of post-processing, lowers operating costs, saves raw material costs, and reduces reaction time by more than 2 times.

[0022] This invention has conducted extensive research on the feeding relationship of materials and process parameters. This process can not only obtain Grignard reagents with a concentration of 1.5-1.7M, but also suppress the occurrence of coupling side reactions. The concentration of coupling byproducts does not exceed 5%, ensuring the concentration and yield of the final product. Attached Figure Description

[0023] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are merely exemplary, and those skilled in the art can derive other embodiments based on the provided drawings without creative effort.

[0024] Figure 1 This is a process flow diagram for continuous batch production of Grignard reagents provided in an embodiment of the present invention. Detailed Implementation

[0025] The following specific embodiments illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0026] In the following examples, the raw material magnesium includes magnesium powder, magnesium shavings, or magnesium granules.

[0027] Example 1

[0028] This embodiment provides a continuous batch process for the production of allyl magnesium chloride, the reaction of which is as follows:

[0029]

[0030] Includes the following steps:

[0031] (1) Three reactors are connected in series by pipelines. 91.5 kg of raw magnesium and 50 L of tetrahydrofuran are added to the first 1000 L reactor, 54.9 kg of raw magnesium and 30 L of tetrahydrofuran are added to the second 500 L reactor, and 0.16 kg of raw magnesium and 10 L of tetrahydrofuran are added to the third 500 L reactor. The temperature of each reactor is lowered to -5 °C and maintained for more than 30 min, and then replaced with an inert atmosphere for later use.

[0032] (2) The raw material allyl chloride and tetrahydrofuran were mixed in a micro mixer to form an allyl chloride solution with a concentration of 2.8M. The allyl chloride solution was continuously fed into the first reactor at a rate of 1L / min. When the temperature and pressure of the first reactor were observed to rise significantly, the temperature of the first reactor rose to 10℃. The cooling water rate was adjusted to maintain the temperature of the first reactor at 10℃. After 30 minutes, the temperature of the first reactor was raised to 30℃. After 1 hour, the allyl chloride solution with a concentration of 2.8M was continuously fed at a rate of 2L / min. After 7 hours, a sample was taken at the outlet of the first reactor to detect that the concentration of allyl magnesium chloride was 1.2M. The reaction liquid in the first reactor was continuously overflowed into the second reactor at a rate of 2L / min.

[0033] (3) After the reaction in the second vessel is observed to have started, i.e. when the temperature of the second vessel rises to 10°C, the cooling water speed is adjusted to maintain the temperature of the second vessel at 10°C. After 10 minutes, the temperature of the second vessel is raised to 30°C. After 3 hours, a sample is taken at the outlet of the second vessel to detect that the concentration of allyl magnesium chloride is 1.4M. The reaction liquid in the second vessel is continuously overflowed into the third vessel at a speed of 2L / min.

[0034] (4) After the reaction in the third reactor is observed to have started, i.e. when the temperature of the third reactor rises to 10°C, adjust the cooling water speed to keep the temperature of the third reactor at 10°C. After 10 minutes, raise the temperature of the third reactor to 30°C. After 1 hour, take a sample at the outlet of the third reactor to test the concentration of allyl magnesium chloride, which is 1.5M. Continue to discharge the material at a rate of 2L / min.

[0035] (5) After the material is settled in the settling tank, the supernatant is introduced into the packaging material.

[0036] The first batch of feed lasted for 13 hours, producing 1700L of 1.5M allyl magnesium chloride tetrahydrofuran solution. After the reaction solution was purified, the organic solution portion was extracted and analyzed by HNMR. The purified product of allyl magnesium chloride was about 95%, and the coupling product 1,5-hexadiene was 3%. The raw material conversion rate reached over 98%.

[0037] Example 2

[0038] This embodiment provides a continuous batch process for producing allyl magnesium chloride, comprising the following steps:

[0039] (1) Three reactors are connected in series by pipelines. 98 kg of raw material magnesium and 50 L of tetrahydrofuran are added to the first 1000 L reactor, 63.5 kg of raw material magnesium and 30 L of tetrahydrofuran are added to the second 500 L reactor, and 0.28 kg of raw material magnesium and 10 L of tetrahydrofuran are added to the third 500 L reactor. The temperature of each reactor is lowered to -10 °C and maintained for more than 30 min, and then replaced with an inert atmosphere for later use.

[0040] (2) The raw material allyl chloride and tetrahydrofuran were mixed in a micro mixer to form an allyl chloride solution with a concentration of 3M. The allyl chloride solution was continuously fed into the first reactor at a rate of 1L / min. When the temperature and pressure of the first reactor were observed to rise significantly, the temperature of the first reactor rose to 12℃. The cooling water rate was adjusted to maintain the temperature of the first reactor at 12℃. After 30 minutes, the temperature of the first reactor was raised to 30℃. After 1 hour, the allyl chloride solution with a concentration of 3M was continuously fed at a rate of 2L / min. After 7 hours, a sample was taken at the outlet of the first reactor to detect that the concentration of allyl magnesium chloride was 1.3M. The reaction liquid in the first reactor was continuously overflowed into the second reactor at a rate of 2L / min.

[0041] (3) After the reaction in the second vessel is observed to have started, i.e. when the temperature of the second vessel rises to 12°C, the cooling water rate is adjusted to maintain the temperature of the second vessel at 12°C. After 10 minutes, the temperature of the second vessel is raised to 30°C. After 3 hours, a sample is taken at the outlet of the second vessel to detect that the concentration of allyl magnesium chloride is 1.5M. The reaction liquid in the second vessel is continuously overflowed into the third vessel at a rate of 2L / min.

[0042] (4) After the reaction in the third reactor is observed to have started, i.e. when the temperature of the third reactor rises to 12°C, adjust the cooling water speed to keep the temperature of the third reactor at 12°C. After 10 minutes, raise the temperature of the third reactor to 30°C. After 1 hour, take a sample at the outlet of the third reactor to test the concentration of allyl magnesium chloride, which is 1.55M. Continue to discharge the material at a rate of 2L / min.

[0043] (5) After the material is settled in the settling tank, the supernatant is introduced into the packaging material.

[0044] The first batch of feed was carried out over 12 hours, producing 1600L of 1.48M tetrahydrofuran solution of allyl magnesium chloride. After the reaction solution was quenched, the organic fraction was extracted and analyzed by HNMR. The quenching product of allyl magnesium chloride was about 93%, and the coupling product 1,5-hexadiene was 4%. The raw material conversion rate was higher than 97%.

[0045] Example 3

[0046] This embodiment provides a continuous batch process for producing benzyl magnesium chloride, comprising the following steps:

[0047] (1) Three reactors are connected in series by pipelines. 90 kg of raw material magnesium and 50 L of tetrahydrofuran are added to the first 1000 L reactor, 55 kg of raw material magnesium and 30 L of tetrahydrofuran are added to the second 500 L reactor, and 0.15 kg of raw material magnesium and 10 L of tetrahydrofuran are added to the third 500 L reactor. The temperature of each reactor is lowered to -10 °C and maintained for more than 30 min, and then replaced with an inert atmosphere for later use.

[0048] (2) The benzyl chloride raw material was dissolved in tetrahydrofuran to prepare a benzyl chloride solution with a concentration of 3M. The benzyl chloride solution was continuously fed into the first reactor at a rate of 1L / min. When the temperature and pressure of the first reactor were observed to rise significantly, the temperature of the first reactor rose to 10℃. The cooling water rate was adjusted to maintain the temperature of the first reactor at 10℃. After 20 minutes, the temperature of the first reactor was raised to 25℃. After 1 hour, a benzyl chloride solution with a concentration of 2.6M was continuously fed at a rate of 2L / min. After 7 hours, a sample was taken at the outlet of the first reactor to detect that the concentration of benzyl magnesium chloride was 1.2M. The reaction liquid in the first reactor was continuously overflowed into the second reactor at a rate of 2L / min.

[0049] (3) After the reaction in the second reactor is observed to have started, i.e. when the temperature of the second reactor rises to 10°C, the cooling water rate is adjusted to maintain the temperature of the second reactor at 10°C. After 10 minutes, the temperature of the second reactor is raised to 25°C. After 3 hours, a sample is taken at the outlet of the second reactor to detect that the concentration of benzyl magnesium chloride is 1.4M. The reaction liquid in the second reactor is continuously overflowed into the third reactor at a rate of 2L / min.

[0050] (4) After the reaction in the third reactor is observed to have started, i.e. when the temperature of the third reactor rises to 10°C, adjust the cooling water speed to keep the temperature of the third reactor at 10°C. After 10 minutes, raise the temperature of the third reactor to 25°C. After 1 hour, take a sample at the outlet of the third reactor to test the concentration of benzyl magnesium chloride, which is 1.5M. Continue to discharge the material at a rate of 2L / min.

[0051] (5) After the material is settled in the settling tank, the supernatant is introduced into the packaging material.

[0052] The first batch of feed lasted for 13 hours, producing 1700L of 1.5M benzyl magnesium chloride tetrahydrofuran solution. After extraction and sterilization, the organic fraction of the reaction solution was extracted and analyzed by gas chromatography. The benzyl chloride content of the raw material was only 0.4%, the coupling byproduct 1,2-diphenylethane was 3.2%, and the benzyl alcohol content of the extraction product of benzyl magnesium chloride reached 93.1%, with a raw material conversion rate of over 97%.

[0053] Although the present invention has been described in detail above with general descriptions and specific embodiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A continuous batch process for producing Grignard reagents, characterized in that, The steps are as follows: Magnesium and organic solvent were added to the first, second and third reactors connected in series, respectively, and the temperature of each reactor was controlled at -10 to 0℃ to replace the atmosphere with an inert atmosphere. A mixture of halogenated hydrocarbons and organic solvents is continuously fed into the first reactor. When the temperature of the first reactor reaches 8-12°C, the cooling water rate is adjusted to maintain the temperature at 8-12°C. After 20-40 minutes, the temperature of the first reactor is raised to 20-30°C. When the concentration of alkyl magnesium halide in the first reactor reaches 1-1.2 M, the material from the first reactor overflows into the second reactor. When the temperature of the second reactor reaches 8-12°C, the cooling water rate is adjusted to maintain the temperature at 8-12°C. The temperature is 8-12℃. After 8-12 minutes, the temperature of the second reactor is raised to 20-30℃. When the concentration of hydrocarbon magnesium halide in the second reactor reaches 1.35-1.5M, the material in the second reactor overflows into the third reactor. When the temperature of the third reactor rises to 8-12℃, the cooling water rate is adjusted to maintain the temperature of the third reactor at 8-12℃. After 8-12 minutes, the temperature of the third reactor is raised to 20-30℃ to obtain a Grignard reagent with a concentration of 1.5-1.7M. In the first reaction vessel, the mass-to-volume ratio of raw material magnesium to organic solvent is (85-100) kg: 50 L; In the second reactor, the mass-to-volume ratio of raw material magnesium to organic solvent is (50-65) kg: 30 L; In the third reaction vessel, the mass-to-volume ratio of raw material magnesium to organic solvent is (0.1-0.3) kg: 10 L; The mass ratio of magnesium raw material in the first, second, and third reaction vessels is (85-100):(50-65):(0.1-0.3); In the mixture of the halogenated hydrocarbon and the organic solvent, the concentration of the halogenated hydrocarbon is 2.5-3M; The total amount of magnesium used in the raw materials and the molar ratio of the halogenated hydrocarbons are 1.2-1.8:1; The halohydrocarbon is allyl chloride or benzyl chloride; The Grignard reagent is allyl magnesium chloride or benzyl magnesium chloride.

2. The continuous batch-type production process for Grignard reagents according to claim 1, characterized in that, A mixture of halogenated hydrocarbons and organic solvents is continuously fed into the first reactor at a rate of 0.8-1.2 L / min. When the temperature of the first reactor reaches 8-12°C, the cooling water rate is adjusted to maintain the temperature at 8-12°C. After 20-40 min, the temperature of the first reactor is raised to 20-30°C. After 55-65 min, the mixture of halogenated hydrocarbons and organic solvents is continuously fed into the first reactor at a rate of 1.8-2.2 L / min. When the concentration of hydrocarbon-based magnesium halide in the first reactor reaches 1-1.2 M, the material from the first reactor is continuously overflowed into the second reactor at a rate of 1.8-2.2 L / min.

3. The continuous batch-type production process for Grignard reagents according to claim 1, characterized in that, When the concentration of hydrocarbon-based magnesium halide in the second reactor reaches 1.35-1.5M, the material in the second reactor is continuously overflowed into the third reactor at a rate of 1.8-2.2L / min.

4. The continuous batch-type production process for Grignard reagents according to claim 1, characterized in that, When the concentration of hydrocarbon-based magnesium halide in the third reaction vessel reaches 1.5-1.7M, it is continuously discharged at a rate of 1.8-2.2L / min to obtain Grignard reagent with a concentration of 1.5-1.7M.

5. The continuous batch-type production process for Grignard reagents according to claim 1, characterized in that, The organic solvent is an ether solvent, or a mixture of an ether solvent and toluene.

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