Method for purifying imazamox

Abstract

The invention discloses an imazamox purification method, which comprises: mixing a crude imazamox product with a solvent, dissolving, carrying out heat preservation for a period of time, cooling, adding a seed crystal, carrying out co-crystal growing for a period of time, cooling, crystallizing, pulping, separating to obtain a primary crystal, mixing the primary crystal with the solvent, re-crystallizing, and drying to obtain the imazamox. Finally, purified imazamox is obtained, and filtrate obtained through separation is subjected to reduced pressure distillation and then serves as a solvent again to be recycled. According to the method, the imazamox crude product is purified into the imazamox product which is high in purity and meets the market requirements through solvent purification, recrystallization and pulping, the yield and the whiteness are improved, the method is suitable for industrial large-scale production, and the production cost and the resource waste are reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of imazamox production, and particularly relates to a method for purifying imazamox. Background Art

[0002] Methoxazolidinone is an imidazolinone herbicide and an inhibitor of acetolactate synthase (ALS) or acetohydroxyacid synthase (AHAs). It is absorbed through leaves, transmitted and accumulated in meristems, inhibiting the activity of AHAS, leading to the cessation of biosynthesis of branched-chain amino acids - valine, leucine and isoleucine, interfering with DNA synthesis, cell mitosis and plant growth, and ultimately causing plant death. Methoxazolidinone is a broad-spectrum post-emergence herbicide for controlling grass weeds in broad-leaved crops. It has a strong killing effect on a variety of annual and perennial weeds, and has little or no activity on dicotyledonous plants or sedges. It is mainly suitable for farmland weeding of more than 40 crops such as soybean, flax, tobacco, watermelon, etc. It can control more than 30 kinds of grass weeds such as barnyard grass, wild oats, foxtail grass, and black foxtail. It also has a good control effect on some difficult-to-control weeds, such as Polygonum convolvulus, Sonchus endive, Mustela, Commelina, Solanum nigrum, etc. After application, the growing points and internode meristems of grass weeds will first turn yellow, brown and necrotic, and the heart leaves will first turn yellow-purple and die, and the weeding will be completed in 5-10 days.

[0003] Chinese patent CN117024406A discloses a method for synthesizing imazamox, which comprises the following steps: ① brominating 5-methyl-2,3-pyridinedicarboxylic acid dimethyl ester to a raw material content of ≤0.5% to obtain a bromide solution containing monobromo and dibromo; ② debrominating the bromide solution obtained in step ① to obtain a monobromo; ③ directly reacting the monobromo obtained in step ② with 2-amino-2,3-dimethylbutyramide and sodium methoxide to obtain imazamox. The method for synthesizing imazamox of the present invention not only greatly improves the reaction conversion rate, thereby obtaining a higher reaction yield, but also greatly reduces the content of by-products, thereby obtaining a higher product purity, and is suitable for large-scale industrial production.

[0004] Chinese patent CN114478477A discloses a synthesis process of imazamox, specifically: (2,3-dimethoxycarbonylpyridin-5-methyl)trimethylammonium bromide is used as a raw material to synthesize imazamox, and after the reaction is completed, trimethylamine is extracted and recovered at a certain temperature and vacuum degree; and the water layer is treated with hydrobromic acid to recover sodium bromide. This synthesis process realizes the recycling of waste trimethylamine and sodium bromide in the synthesis process of imazamox, and at the same time realizes a significant improvement in the yield of imazamox, which is more environmentally friendly and efficient, greatly reduces production costs, and is more conducive to the industrial production of imazamox.

[0005] Chinese patent CN118047751A discloses a method for preparing imazamox, which has the following steps: ① adding 5-methyl-2,3-pyridinedicarboxylic acid dimethyl ester, organic base, diethyl phosphite and dichloroethane to a reaction device, stirring and dissolving, heating to 60-70°C, then adding N-bromoamide brominating agent and azobisisobutyronitrile in batches, heating to reflux reaction until complete, and obtaining 5-bromomethyl-2,3-pyridinedicarboxylic acid dimethyl ester; ② directly reacting the 5-bromomethyl-2,3-pyridinedicarboxylic acid dimethyl ester obtained in step ① with 2-amino-2,3-dimethylbutyramide and sodium methoxide to obtain imazamox. The method for preparing imazamox of the present invention can not only obtain a higher reaction yield and product purity, but also omit the debromination treatment step, the reaction step is shorter, the operation is simpler, especially the amount of brominating agent is lower, the production cost is lower, and it is more suitable for industrial large-scale production.

[0006] However, in industrial production, due to reasons such as process, raw materials and human errors, a part of the synthesized methoxazole exists in the mother liquor. After the mother liquor is recovered, the methoxazole product can be obtained, but the content does not meet the standard, only 70-80%, and contains a large amount of impurities, which makes it not meet market requirements. Summary of the invention

[0007] In view of the above technical problems, the present invention provides a method for purifying imazamox, which utilizes solvent purification, crystallization, and pulping to purify crude imazamox into a high-purity imazamox product that meets market requirements, and improves the yield and whiteness, is suitable for industrial large-scale production, and reduces production costs and resource waste.

[0008] In order to achieve the above object, the present invention provides a method for purifying imazamox, comprising the following steps: (1) adding crude imazamox to a solvent, stirring and mixing, and heating to dissolve the mixture to obtain a first mixed solution; (2) the first mixed solution is stirred at a constant temperature, then cooled to 40-45° C., imazamox seed crystals are added, and crystals are grown at a constant temperature for 8-15 minutes, then cooled to crystallize, thereby obtaining a second mixed solution; (3) The two mixed solutions are separated after pulping to obtain a primary crystal and a primary filtrate; (4) Repeating steps (1) to (3) 2 to 5 times for primary crystallization to obtain purified crystals and filtrate; (5) purifying, crystallizing and drying to obtain purified imazamox; (6) The filtrates from steps (3) and (4) are collected, mixed, and concentrated under reduced pressure to obtain a solvent, which is returned to step (1) for recycling.

[0009] Preferably, the mass ratio of the crude imazamox to the solvent in step (1) is 1:2-6.

[0010] Further preferably, the mass concentration of imazamox in the crude imazamox product is 70-80%.

[0011] More preferably, the solvent is any one of methanol, acetonitrile, toluene, acetone and ethyl acetate.

[0012] Preferably, the mixing temperature in step (1) is 50-110°C.

[0013] Preferably, the cooling rate in step (2) is 2-5°C / min; and the amount of the imazamox seed crystals added is 0.5%-3% of the crude imazamox quality.

[0014] Further preferably, the imazamox crystal seed is any one of a crude imazamox product, a crystalline product of imazamox and a purified imazamox product.

[0015] Preferably, the beating speed in step (3) is 600-1000 rpm / min, and the beating time is 2-5 h.

[0016] Preferably, the separation method in step (3) is filtration, and more preferably, the filtration is suction filtration; the drying condition in step (5) is drying at 75-95° C. for 3-6 hours.

[0017] Preferably, the vacuum distillation pressure of the filtrate in step (6) is -0.085 MPa to -0.095 MPa, and the temperature is 45-55°C.

[0018] The beneficial effects of the present invention are: 1. The crude imipenem product is mixed with a solvent, heated to dissolve, then kept warm, cooled, seed crystals are added to grow crystals, and then cooled to crystallize, and finally a primary crystal is obtained by pulping and separation, and then the above steps are repeated for the primary crystal for multiple times to prepare a purified imipenem product with a purity of more than 99%, effectively controlling the content of imipenem, and effectively reducing the negative impact of imipenem during the use of the imipenem product. In addition, the whiteness and yield of the product are improved, so that the imipenem product has higher economic value and a wider range of application scenarios.

[0019] 2. Adding crystal seeds during the crystallization process increases the crystallization rate, shortens the purification time, and is conducive to industrial utilization.

[0020] 3. The solvent used in the purification process is subjected to reduced pressure distillation and then recovered to achieve solvent recycling, thereby reducing the purification cost without affecting the purification effect. DETAILED DESCRIPTION

[0021] The technical solution of the present invention is further explained below in conjunction with specific embodiments. It is worth noting that the following embodiments are only preferred embodiments of the present invention and should not be construed as limiting the present invention. The protection scope of the present invention shall be subject to the contents recorded in the claims. Any modification or replacement made by a person skilled in the art to the technical solution of the present invention without creative work shall fall within the protection scope of the present invention.

[0022] Example 1 (1) placing a crude imazamox product with a purity of 76.52% (recovered from the mother liquor of producing imazamox) in a container, adding acetonitrile, heating the solution in a water bath to 80° C., and stirring the solution until the solid is dissolved and clarified, thereby obtaining a first mixed solution; wherein the mass ratio of the crude imazamox product to the acetonitrile is 1:3; (2) The first mixed solution is kept warm and stirred, and after 1 hour, the temperature is lowered to 45°C at a rate of 2°C / min, and then imazamox seed crystals are added, and the crystals are grown at a constant temperature of 45°C for 10 minutes, and then the temperature is lowered to room temperature at a rate of 2°C / min to obtain a second mixed solution; wherein the amount of the imazamox seed crystals added is 1% of the quality of the crude imazamox in step (1), and the imazamox seed crystals are crude imazamox; (3) The second mixed solution was slurried at 800 rpm / min for 3 h, and after slurrying, it was filtered to obtain a primary filtrate and a primary crystal; (4) remixing the primary crystals with the solvent, and repeating steps (1) to (3) twice to obtain purified crystals and a filtrate; the seed crystals used in the secondary crystallization are the primary crystallization product; and the seed crystals added in the tertiary crystallization are the secondary crystallization product; (5) drying the purified crystals at 85° C. for 5 h to obtain purified imazamox; (6) The filtrates from steps (3) and (4) were collected and subjected to reduced pressure distillation at 50° C. and −0.090 MPa to obtain an acetonitrile solution, which was used as a solvent in the dissolution and purification process of imazamox.

[0023] Example 2 The method and steps are the same as those in Example 1, except that the acetonitrile in step (1) is replaced by ethyl acetate and the temperature is changed to 70° C. to prepare purified imazamox.

[0024] Example 3 The method and steps are the same as those in Example 1, except that the acetonitrile in step (1) is replaced by toluene and the temperature is changed to 100° C. to prepare purified imazamox.

[0025] Example 4 The method and steps are the same as those in Example 1, except that the acetonitrile in step (1) is replaced by acetone and the temperature is changed to 50° C. to prepare purified imazamox.

[0026] Example 5 The method and steps are the same as those in Example 1, except that the cooling rate in step (2) is changed to 5°C / min, and the number of repetitions in step (4) is changed to 5 times, to prepare purified imazamox.

[0027] Example 6 The method and steps are the same as those in Example 1, except that the mass ratio of crude imazamox to acetonitrile in step (1) is changed to 1:4 to prepare purified imazamox.

[0028] Example 7 The method and steps are the same as those in Example 1, except that all the seed crystals added during crystallization are replaced with purified imazamox seed crystals, and the amount of seed crystals added is changed to 3%.

[0029] Comparative Example 1 The method and steps are the same as those in Example 1, except that the temperature in step (1) is changed to 90° C. to prepare purified imazamox.

[0030] Comparative Example 2 The method and steps are the same as those in Example 1, except that no seed crystals are added in step (2), thereby preparing purified imazamox.

[0031] Comparative Example 3 The method and steps are the same as those in Example 1, except that in step (2), no seed crystals are added and the temperature is lowered to room temperature once to prepare purified imazamox.

[0032] Comparative Example 4 The method and steps are the same as those in Example 1, except that the acetonitrile in step (1) is replaced by ethanol and the temperature is changed to 75° C. to prepare purified imazamox.

[0033] Comparative Example 5 The method and steps are the same as those in Example 1, except that the mass ratio of the crude imazamox to acetonitrile in step (1) is changed to 1:1, thereby preparing purified imazamox.

[0034] Comparative Example 6 The method and steps are the same as those in Example 1, except that the mass ratio of the crude imazamox to acetonitrile in step (1) is changed to 1:7 to prepare purified imazamox.

[0035] Comparative Example 7 The method and steps are the same as those in Example 1, except that step (4) is omitted, and purified imazamox is directly prepared.

[0036] Result detection: The purified imazamox prepared in the above examples and comparative examples were taken, and the performance indicators and impurity content of imazamox were detected with reference to the agricultural industry standard NY / T 4090-2022 of the People's Republic of China, and the yield was statistically analyzed. The results are as follows:

[0037] Note: The impurity is imipenem.

[0038] The results showed that different solvents had different purification effects on imazamox. When acetonitrile was used as the solvent, the purity and whiteness of the obtained imazamox were the best, which met the market requirements. In addition, with the increase of solvent dosage, the purity of the product increased, but the increase slowed down and tended to be stable, and the yield decreased. Therefore, the optimal mass ratio of imazamox to solvent was 1:3.

Claims

1. A method for purifying imazamox, characterized in that: The steps include: (1) adding crude imazamox to a solvent, stirring and mixing, and heating to dissolve the mixture to obtain a first mixed solution; (2) the first mixed solution is stirred at a constant temperature, then cooled to 40-45° C., imazamox seed crystals are added, and crystals are grown at a constant temperature for 8-15 minutes, then cooled to crystallize, thereby obtaining a second mixed solution; (3) The second mixed solution is separated after pulping to obtain a primary crystal and a primary filtrate; (4) Repeating steps (1) to (3) 2 to 5 times for primary crystallization to obtain purified crystals and filtrate; (5) purifying, crystallizing and drying to obtain purified imazamox; (6) The filtrates from steps (3) and (4) are collected, mixed, and concentrated under reduced pressure to obtain a solvent, which is returned to step (1) for recycling.

2. The method for purifying imazamox according to claim 1, characterized in that: The mass ratio of the crude imazamox product to the solvent in step (1) is 1:2-6.

3. The method for purifying imazamox according to claim 2, characterized in that: The mass concentration of imazamox in the crude imazamox product is 70-80%.

4. The method for purifying imazamox according to claim 2, characterized in that: The solvent is any one of methanol, acetonitrile, toluene, acetone and ethyl acetate.

5. The method for purifying imazamox according to claim 1, characterized in that: The temperature after heating in step (1) is 50-110°C.

6. The method for purifying imazamox according to claim 1, characterized in that: The cooling rate in step (2) is 2-5°C / min; the amount of the imazamox seed crystals added is 0.5%-3% of the crude imazamox quality.

7. The method for purifying imazamox according to claim 1, characterized in that: The stirring speed during the beating in step (3) is 600-1000 rpm / min, and the beating time is 2-5 hours.

8. The method for purifying imazamox according to claim 1, characterized in that: The drying condition in step (5) is drying at 75-95°C for 3-6 hours.

9. The method for purifying imazamox according to claim 1, characterized in that: The pressure of the reduced pressure distillation in step (6) is -0.085Mpa~-0.095Mpa, and the temperature is 45-55°C.

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