Method for purifying fluroxypyr-mepthyl

Abstract

The invention relates to the field of organic synthesis, in particular to a fluroxypyr-mepthyl purification method which comprises the step of adjusting the pH value of a solution to 3-5 in the crystallization process. According to the method, impurities in the product can be effectively removed, and the purity of the product can reach 99% or above. The method disclosed by the invention is environment-friendly, simple and convenient to operate, easy to control in operation, low in cost, good in economic benefit and suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and in particular to a method for purifying isooctyl chloropyroxyacetate. Background Technology

[0002] Isooctyl chlorpyrifos, also known as fluroxypyr octyl chlorpyrifos, is a highly effective, systemic post-emergence foliar herbicide. Developed by Dow AgroSciences in 1985, this compound was first registered in China in 1991. Chemically, it belongs to the pyridineoxyacetic acid class of herbicides; its mechanism of action is that of a typical hormone-type herbicide, rapidly absorbed by the leaves and roots of weeds and translocated throughout the entire plant, causing sensitive weeds to exhibit deformities, twisting, and ultimately die.

[0003] Isooctyl chlorpyrifos is mainly suitable for crops such as wheat, barley, corn, and orchards, used to control various noxious broadleaf weeds such as water hyacinth and field bindweed, and it is safe for subsequent crops with no residue. Due to its strong selectivity, broad spectrum of weed control, and safety for gramineous crops, this product has been widely used globally. Currently, 31 companies in my country have registered for the production of the technical grade, making it an important product in the field of broadleaf weed control.

[0004] Regarding the preparation method of isooctyl clopyroxyacetate, US3761486A discloses a method using pyridine as a starting material. First, pentachloropyridine is generated through a chlorination reaction, followed by fluorination and amination steps to prepare the key intermediate 4-amino-3,5-dichloro-2,6-difluoropyridine. This intermediate then undergoes a condensation reaction with 2-octyl glycolate to finally synthesize the target product, isooctyl clopyroxyacetate. This route has relatively few synthetic steps, a simple process flow, and is easy to operate. However, this process also has significant drawbacks: the yield of its core condensation reaction step is low, resulting in low purity of the final product, which to some extent affects the economics and product quality of its industrial production.

[0005] In addition, the prior art also discloses the direct etherification of potassium 4-amino-3,5-dichloro-6-fluoropyridine-2-phenol with 2-octyl chloroacetate to obtain isooctyl chlorophenoxyacetate. This route is simple to operate, but its yield is not high and the purity of the product is low. The product mainly contains the following two byproducts, of which byproduct (1) is obtained by the reaction of the amino group in potassium 4-amino-3,5-dichloro-6-fluoropyridine-2-phenol with 2-octyl chloroacetate, and byproduct (2) is generated by the hydrolysis of isooctyl chlorophenoxyacetate. Summary of the Invention

[0006] To address the above problems, this invention provides a method for purifying isooctyl clopyralid, the method comprising the following steps: S1: Dissolve crude isooctyl clopyralid in organic solvent 1 and heat to dissolve isooctyl clopyralid; S2: Add pH adjuster to adjust the pH of the solution to 3-5; S3: Add activated carbon for decolorization, then filter; S4: Cool the filtrate obtained in step S3, crystallize it, filter it, wash it, and dry it to obtain isooctyl clopyralid.

[0007] Preferably, the organic solvent 1 is selected from one or more of methanol, ethanol and isopropanol; preferably from ethanol.

[0008] Preferably, the mass-to-volume ratio of crude chloropyroxyacetic acid isooctyl ester to organic solvent 1 is 1:2-1:5; more preferably 1:2-1:3, g / mL.

[0009] Preferably, the heating temperature in step S1 is 40-80℃, and more preferably 50-70℃.

[0010] Preferably, the pH adjuster is selected from one or more of dilute hydrochloric acid, acetic acid, benzoic acid and oxalic acid; preferably acetic acid.

[0011] Preferably, in step S2, the pH value is adjusted to 3.5-4.5.

[0012] Preferably, the method for preparing the crude clopyralid isooctyl ester includes: , Step Sa: Compound 1 and Compound 2 undergo a substitution reaction to yield isooctyl chloropyroxyacetate.

[0013] Preferably, step Sa is carried out in organic solvent 2.

[0014] Preferably, the organic solvent 2 is selected from one or more of DMF, pyridine, NMP, ethanolamine and HMDS, and more preferably from one or more of DMF and NMP.

[0015] Preferably, the reaction temperature of step Sa is 50-80℃.

[0016] Preferably, in step S4, the filtrate obtained in step S3 is cooled to 0-10°C to crystallize.

[0017] The effects of the invention The purification method described in this invention adjusts the pH of the solution to acidic 3-5 during recrystallization, which effectively removes impurities from the product and improves its purity. The isooctyl clopyralid prepared by the method described in this invention achieves a purity of over 99%.

[0018] The method described in this invention is environmentally friendly, easy to operate, easy to control, low in cost, and has good economic benefits, making it suitable for industrial production. Detailed Implementation

[0019] To make the technical solution and beneficial effects of the present invention more apparent and understandable, a detailed description is provided below by listing specific embodiments. Unless otherwise defined, the technical and scientific terms used herein have the same meanings as those in the technical field to which this application pertains.

[0020] This invention provides a method for purifying isooctyl clopyralid, the method comprising the steps of: S1: Dissolve crude isooctyl clopyralid in organic solvent 1 and heat to dissolve isooctyl clopyralid; S2: Add pH adjuster to adjust the pH of the solution to 3-5; S3: Add activated carbon for decolorization, then filter; S4: Cool the filtrate obtained in step S3, crystallize it, filter it, wash it, and dry it to obtain isooctyl clopyralid.

[0021] In some embodiments, the organic solvent 1 is selected from one or more of methanol, ethanol, and isopropanol.

[0022] In some embodiments, the organic solvent 1 is selected from ethanol.

[0023] In some embodiments, the mass-to-volume ratio of crude chloropyroxyacetic acid isooctyl ester to organic solvent 1 is 1:2-1:5, g / mL.

[0024] In some embodiments, the mass-to-volume ratio of crude chloropyroxyacetic acid isooctyl ester to organic solvent 1 is 1:2-1:3, g / mL.

[0025] In some embodiments, the mass-to-volume ratio of the crude isooctyl chloropyroxyacetate to organic solvent 1 is 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, or 1:3, g / mL.

[0026] In some embodiments, the heating temperature in step S1 is 40-80°C.

[0027] In some embodiments, the heating temperature in step S1 is 50-70°C.

[0028] In some embodiments, the heating temperature in step S1 is 50°C, 51°C, 52°C, 53°C, 54°C, 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C, or 70°C.

[0029] In some embodiments, the pH adjuster is selected from one or more of dilute hydrochloric acid, acetic acid, benzoic acid, and oxalic acid.

[0030] In some embodiments, the pH adjuster is selected from acetic acid.

[0031] In some implementations, the pH value is adjusted to 3.5-4.5 in step S2.

[0032] In some implementations, the pH value is adjusted to 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, or 4.5 in step S2.

[0033] In some embodiments, the mass ratio of crude clopyralid isooctyl ester to activated carbon in step S3 is 1:1%-5%.

[0034] In some embodiments, the mass ratio of crude clopyralid isooctyl ester to activated carbon in step S3 is 1:1%-3%.

[0035] In some embodiments, the mass ratio of crude clopyralid isooctyl ester to activated carbon in step S3 is 1:1%, 1:1.1%, 1:1.2%, 1:1.3%, 1:1.4%, 1:1.5%, 1:1.6%, 1:1.7%, 1:1.8%, 1:1.9%, 1:2.0%, 1:2.1%, 1:2.2%, 1:2.3%, 1:2.4%, 1:2.5%, 1:2.6%, 1:2.7%, 1:2.8%, 1:2.9%, or 1:3.0%.

[0036] In some embodiments, the method for preparing the crude clopyralid isooctyl ester includes: Step Sa: Compound 1 and Compound 2 undergo a substitution reaction to yield isooctyl chloropyroxyacetate.

[0037] In some embodiments, step Sa is carried out in organic solvent 2.

[0038] In some embodiments, the organic solvent 2 is selected from one or more of DMF, pyridine, NMP, ethanolamine, and HMDS.

[0039] In some embodiments, the organic solvent 2 is selected from one or more of DMF and NMP.

[0040] In some embodiments, the organic solvent 2 is selected from DMF.

[0041] In some embodiments, the reaction temperature of step Sa is 50-80°C.

[0042] In some embodiments, the reaction temperature of step Sa is 50-70°C.

[0043] In some embodiments, the reaction temperature of step Sa is 50°C, 51°C, 52°C, 53°C, 54°C, 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C, or 70°C.

[0044] In some embodiments, the preparation method of the crude isooctyl clopyralid includes: reacting compound 1 and compound 2 in DMF at a temperature of 50-70°C; after the reaction is complete, adding water to the reaction solution, heating to 80-90°C and maintaining for 1-2 hours, pouring the reaction solution into ice water, crystallizing, and filtering to obtain the crude isooctyl clopyralid.

[0045] In some embodiments, the molar ratio of compound 1 to compound 2 is 1:1-4.

[0046] In some embodiments, the molar ratio of compound 1 to compound 2 is 1:1-2.

[0047] In some embodiments, the molar ratio of compound 1 to compound 2 is 1:1.5.

[0048] In some embodiments, in step S4, the filtrate obtained in step S3 is cooled to 0-10°C to crystallize.

[0049] In some embodiments, the filtrate obtained in step S3 in step S4 is cooled to 0-5°C for crystallization.

[0050] The method of the present invention will be described below through specific embodiments. It should be understood that these embodiments are used to illustrate the basic principles, main features and advantages of the present invention, and the present invention is not limited to the scope of the following embodiments. The implementation conditions used in the embodiments can be further adjusted according to specific requirements, and the implementation conditions not specified are usually the conditions in conventional experiments.

[0051] In the following examples, unless otherwise specified, all temperatures are in Celsius; unless otherwise specified, all starting materials and reagents are commercially available or synthesized according to known methods; commercially available materials and reagents are used directly without further purification; unless otherwise specified, commercially available manufacturers include, but are not limited to, TCI (Shanghai) Chemical Industry Development Co., Ltd., Bailingwei Technology Co., Ltd., Sinopharm Group, Shanghai BIDE Pharmaceutical Technology Co., Ltd., and Shanghai Mairui Chemical Technology Co., Ltd.

[0052] Unless otherwise specified in the examples, the solution in the reaction refers to an aqueous solution.

[0053] Unless otherwise specified in the examples, the reaction temperature is room temperature, which is 20℃~30℃.

[0054] The reaction process in the examples was monitored using thin-layer chromatography (TLC). The developing solvent used in the reaction, the eluent system used for column chromatography to purify the compounds, or the developing solvent system for TLC included: A: petroleum ether and ethyl acetate system; B: dichloromethane and methanol system; C: n-hexane: ethyl acetate. The volume ratio of the solvent varied depending on the polarity of the compound and could also be adjusted by adding a small amount of acidic or basic reagents, such as acetic acid or triethylamine.

[0055] TLC: Thin-layer chromatography. Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates are used for TLC. The silica gel plates used in TLC have a diameter of 0.2mm-0.3mm, while those used for separating and purifying products are 0.4mm-0.5mm.

[0056] Column chromatography typically uses Yantai Huanghai silica gel with a mesh size of 200-300 as the carrier.

[0057] Example 1: Preparation of crude isooctyl clopyralid. , Compound 1 (23.39 g, 0.1 mol), compound 2 (30.92 g, 0.15 mol), and 80 mL of DMF were added to a reaction flask. The mixture was heated to 55 °C and stirred until the reaction was complete. Then, 100 mL of water was added to the reaction solution, and the mixture was heated to 80 °C and maintained for 1-2 hours. The reaction solution was then poured into ice water to crystallize. After filtration, the filter cake yielded 36.24 g of crude isooctyl clopyralid with a purity of 90.9%.

[0058] Example 2 Purification of isooctyl clopyralid Add 5g of crude isooctyl clopyralid to a reaction flask, add 10mL of ethanol, heat to 55℃ to dissolve the isooctyl clopyralid, adjust the pH of the solution to 3.0 with acetic acid, add 0.1g of activated carbon, stir for 10min, hot filter to obtain filtrate, cool the filtrate to 5℃ to crystallize, filter, wash the filter cake with ethanol solution, dry, and obtain 4.35g of isooctyl clopyralid with a purity of 99.45%.

[0059] Example 3 Purification of isooctyl clopyralid Add 5g of crude isooctyl clopyralid to a reaction flask, add 10mL of ethanol, heat to 55℃ to dissolve the isooctyl clopyralid, adjust the pH of the solution to 3.5 with acetic acid, add 0.1g of activated carbon, stir for 10min, hot filter to obtain filtrate, cool the filtrate to 5℃ to crystallize, filter, wash the filter cake with ethanol solution, dry, and obtain 4.41g of isooctyl clopyralid with a purity of 99.71%.

[0060] Example 4 Purification of isooctyl clopyralid Add 5g of crude isooctyl clopyralid to a reaction flask, add 10mL of ethanol, heat to 55℃ to dissolve the isooctyl clopyralid, adjust the pH of the solution to 4.0 with acetic acid, add 0.1g of activated carbon, stir for 10min, hot filter to obtain filtrate, cool the filtrate to 5℃ to crystallize, filter, wash the filter cake with ethanol solution, dry, and obtain 4.44g of isooctyl clopyralid with a purity of 99.66%.

[0061] Example 4 Purification of isooctyl clopyralid Add 5g of crude clopyralid isooctyl ester to a reaction flask, add 10mL of ethanol, heat to 55℃ to dissolve clopyralid isooctyl ester, adjust the pH of the solution to 4.5 with acetic acid, add 0.1g of activated carbon, stir for 10min, hot filter to obtain filtrate, cool the filtrate to 5℃ to crystallize, filter, wash the filter cake with ethanol solution, dry, and obtain 4.31g of clopyralid isooctyl ester with a purity of 99.69%.

[0062] Example 5 Purification of clopyralid isooctyl ester Add 5g of crude clopyralid isooctyl ester to a reaction flask, add 10mL of ethanol, heat to 55℃ to dissolve clopyralid isooctyl ester, adjust the pH of the solution to 5.0 with acetic acid, add 0.1g of activated carbon, stir for 10min, hot filter to obtain filtrate, cool the filtrate to 5℃ to crystallize, filter, wash the filter cake with ethanol solution, dry, and obtain 4.38g of clopyralid isooctyl ester with a purity of 99.38%.

[0063] Example 6 Purification of isooctyl clopyralid Add 5g of crude isooctyl clopyralid to a reaction flask, add 10mL of ethanol, heat to 55℃ to dissolve the isooctyl clopyralid, adjust the pH of the solution to 5.5 with acetic acid, add 0.1g of activated carbon, stir for 10min, hot filter to obtain filtrate, cool the filtrate to 5℃ to crystallize, filter, wash the filter cake with ethanol solution, dry, and obtain 4.39g of isooctyl clopyralid with a purity of 98.21%.

[0064] Example 7 Purification of isooctyl clopyralid Add 5g of crude isooctyl clopyralid to a reaction flask, add 10mL of tetrahydrofuran, heat to 60℃ to dissolve isooctyl clopyralid, adjust the pH of the solution to 3.5 with acetic acid, add 0.1g of activated carbon, stir for 10min, hot filter to obtain filtrate, cool the filtrate to 5℃ to crystallize, filter, wash the filter cake with ethanol solution, dry, and obtain 4.22g of isooctyl clopyralid with a purity of 98.33%.

[0065] Example 8 Purification of isooctyl clopyralid Add 5g of crude isooctyl clopyralid to the reaction flask, add 10mL of ethanol, heat to 55℃ to dissolve isooctyl clopyralid, add 0.1g of activated carbon, stir for 10min, hot filter to obtain filtrate, cool the filtrate to 5℃ to crystallize, filter, wash the filter cake with ethanol solution, dry, and obtain 4.26g of isooctyl clopyralid with a purity of 98.05%.

[0066] It should be understood that the above embodiments are exemplary and are not intended to encompass all possible implementations included in the claims. Various modifications and changes can be made to the above embodiments without departing from the scope of the invention. Similarly, the various technical features of the above embodiments can be arbitrarily combined to form other embodiments of the invention that may not be explicitly described. Therefore, the above embodiments only illustrate several implementations of the invention and do not limit the scope of protection of this patent.

Claims

1. A method for purifying isooctyl clopyralid, characterized in that, The method includes the following steps: S1: Dissolve crude isooctyl clopyralid in organic solvent 1 and heat to dissolve isooctyl clopyralid; S2: Add pH adjuster to adjust the pH of the solution to 3-5; S3: Add activated carbon for decolorization, then filter; S4: Cool the filtrate obtained in step S3, crystallize it, filter it, wash it, and dry it to obtain isooctyl clopyralid.

2. The method according to claim 1, characterized in that, The organic solvent 1 is selected from one or more of methanol, ethanol and isopropanol; preferably ethanol.

3. The method according to claim 1 or 2, characterized in that, The mass-to-volume ratio of crude chloropyroxyacetic acid isooctyl ester to organic solvent 1 is 1:2-1:5; preferably 1:2-1:3, g / mL.

4. The method according to claim 1 or 2, characterized in that, The heating temperature in step S1 is 40-80℃, preferably 50-70℃.

5. The method according to claim 1 or 2, characterized in that, The pH adjuster is selected from one or more of dilute hydrochloric acid, acetic acid, benzoic acid, and oxalic acid; preferably acetic acid.

6. The method according to claim 1 or 2, characterized in that, In step S2, adjust the pH value to 3.5-4.

5.

7. The method according to claim 1 or 2, characterized in that, The method for preparing the crude clopyralid isooctyl ester includes: ， Step Sa: Compound 1 and Compound 2 undergo a substitution reaction to yield isooctyl chloropyroxyacetate.

8. The method according to claim 1 or 2, characterized in that, Step Sa is carried out in organic solvent 2; Preferably, the organic solvent 2 is selected from one or more of DMF, pyridine, NMP, ethanolamine and HMDS, and more preferably from one or more of DMF and NMP.

9. The method according to claim 8, characterized in that, The reaction temperature for step Sa is 50-80℃.

10. The method according to claim 1 or 2, characterized in that, In step S4, the filtrate obtained in step S3 is cooled to 0-10℃ to induce crystallization. Preferably, the filtrate obtained in step S3 is cooled to 0-5°C for crystallization.

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