阅读说明：本技术 一种制备硝磺草酮类除草剂的方法 (Method for preparing mesotrione herbicide ) 是由 李慧超 关爱莹 芦志成 叶艳明 杨萌 刘鹏飞 刘长令 于 2020-06-28 设计创作，主要内容包括：本发明属于化工领域,具体涉及一种制备硝磺草酮类除草剂的方法。将1,3-环己二酮和酰氯A在路易斯酸和有机溶剂存在下反应,制得目标产物硝磺草酮。本发明反应温和,操作简单,无含氰废水产生,且收率高,产品纯度好。(The invention belongs to the field of chemical industry, and particularly relates to a method for preparing mesotrione herbicide. Reacting 1, 3-cyclohexanedione with acyl chloride A in the presence of Lewis acid and an organic solvent to obtain a target product mesotrione. The method has the advantages of mild reaction, simple operation, no generation of cyanide-containing wastewater, high yield and good product purity.)

1. A process for the preparation of mesotrione-type herbicides, which comprises: 1, 3-cyclohexanedione and acyl chloride A react in the presence of Lewis acid and an organic solvent to prepare a target product.

2. The process for preparing mesotrione and analogues thereof according to claim 1, wherein: the acyl chloride A is selected from any one of A1-A9,

3. the process for the preparation of a mesotrione-type herbicide as claimed in claim 1 or claim 2, wherein: adding acyl chloride A into a suspension of Lewis acid and a solvent, dissolving to obtain a solution, dissolving 1, 3-cyclohexanedione in the solvent, dripping into the solution, reacting at 0-room temperature for 0.5-5 hours, reacting at room temperature-60 ℃ for 2-8 hours, and performing post-treatment and purification to obtain the target product mesotrione and the like.

4. A process for the preparation of a mesotrione-type herbicide as claimed in claim 3, wherein: the dissolving solution is as follows: adding acyl chloride A into the suspension of Lewis acid and solvent at the temperature of minus 10 ℃ to room temperature, and dissolving the acyl chloride to obtain a solution for later use.

5. The process for the preparation of a mesotrione-based herbicide as claimed in claim 1, wherein: the temperature of the reaction system is 0-20 ℃ before the 1, 3-cyclohexanedione solution is dripped; after the dripping of the 1, 3-cyclohexanedione solution, reacting at 10 ℃ to room temperature for 1-2 hours, and then reacting at 35-45 ℃ for 2-5 hours.

6. The process for the preparation of a mesotrione-based herbicide as claimed in claim 1, wherein: and after the reaction is finished, dropwise adding water, stirring at the temperature from room temperature to the reflux temperature of the solvent until the solid is completely dissolved, cooling to room temperature, separating, extracting, desolventizing the organic phase to obtain a crude product, and finally purifying to obtain the mesotrione and the analogues thereof.

7. The process for the preparation of a mesotrione-based herbicide as claimed in claim 1, wherein: the solvent is selected from dichloromethane, 1, 2-dichloroethane or chloroform; the Lewis acid is selected from aluminum trichloride; the mol ratio of acyl chloride A, 1, 3-cyclohexanedione and Lewis acid is 1: 1-1.2: 3-5.

8. The process for the preparation of a mesotrione-based herbicide as claimed in claim 7, wherein: the solvent is selected from 1, 2-dichloroethane; the mol ratio of acyl chloride A, 1, 3-cyclohexanedione and Lewis acid is 1: 1-1.2: 3-3.5.

9. A process for the preparation of a mesotrione-type herbicide as claimed in claim 3, wherein: after the reaction is finished, dropwise adding water under an ice bath condition, and stirring at the temperature of 30-60 ℃ until the solid is completely dissolved.

Technical Field

The invention belongs to the field of chemical industry, and particularly relates to a method for preparing mesotrione herbicide.

Background

The mesotrione is a p-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor herbicide, is mainly used for preventing and removing weeds in corn fields, has the characteristics of wide weeding spectrum, good environmental compatibility, low toxicity to mammals and aquatic organisms and the like, and has large market demand and wide application prospect.

Patents CN106565556, US4780127 et al report processes for the preparation of mesotrione, all with the participation of a cyanogenic compound. In the methods disclosed in patents CN1272837, CN101735119, CN105712912, CN110818601, and CN110256308, etc., triazole, purine, tetramethylguanidine, etc. are used as a translocating agent, but these methods have problems of hydrolysis of enol ester, low yield, etc. as proved by experiments.

Patent CN105693569 discloses a method for preparing 3- [4- (methylsulfonyl) -2-chlorobenzoyl ] bicyclo [3.2.1] -octane-2, 4-dione in the presence of lewis acid, but when preparing mesotrione according to the patent method, acidic gas is released in the reaction, a large amount of sticky substances are generated, stirring is not easy, a large amount of hydrochloric acid is required to be added for dissolving sticky solids generated in the reaction during post-treatment, black insoluble substances influence the yield and purity, and side reactions are generated.

Further, a preparation method of mesotrione, which has the advantages of mild reaction, easy operation, less by-products, high conversion rate, high yield and high product purity, is needed.

Disclosure of Invention

The invention aims to provide a preparation method of mesotrione, which has simple synthesis process and high yield and does not use a high-toxicity translocating agent.

In order to achieve the purpose, the invention adopts the technical scheme that:

a process for preparing mesotrione herbicide comprises reacting 1, 3-cyclohexanedione and its analogues with an acid chloride represented by A1-A9 in the presence of a Lewis acid and an organic solvent to obtain the target product.

The 1, 3-cyclohexanedione analogue is any one of acyl chlorides shown as A1-A9,

further, 2-nitro-4-methylsulfonylbenzoyl chloride is added into a suspension of Lewis acid and a solvent to be dissolved to obtain a solution, 1, 3-cyclohexanedione and analogues thereof are dissolved into the solvent and dripped into the solution, the mixture reacts at 0-room temperature for 0.5-5 hours after dripping, and then reacts at room temperature-60 ℃ for 2-8 hours to obtain the target product mesotrione herbicide.

The dissolving solution is as follows: adding 2-nitro-4-methylsulfonylbenzoyl chloride into a suspension of Lewis acid and a solvent at a temperature of-10 ℃ to room temperature, and dissolving the acyl chloride to obtain a solution for later use.

The temperature of the reaction system is 0-20 ℃ before the 1, 3-cyclohexanedione solution is dripped; after the dripping of the 1, 3-cyclohexanedione solution, reacting at 10 ℃ to room temperature for 1-2 hours, and then reacting at 35-45 ℃ for 2-5 hours.

And after the reaction is finished, dropwise adding water, stirring at the temperature from room temperature to the reflux temperature of the solvent until the solid is completely dissolved, cooling to room temperature, separating, extracting, desolventizing the organic phase to obtain a crude product, and finally purifying to obtain the mesotrione herbicide.

The solvent is selected from dichloromethane, 1, 2-dichloroethane or chloroform; the Lewis acid is selected from aluminum trichloride, and the dosage (mole number) of the aluminum trichloride is 3-5 times of that of the 1, 3-cyclohexanedione; the mol ratio of the 2-nitro-4-methylsulfonylbenzoyl chloride to the 1, 3-cyclohexanedione to the Lewis acid is 1: 1-1.2: 3-5.

The solvent is selected from 1, 2-dichloroethane; the mol ratio of the 2-nitro-4-methylsulfonylbenzoyl chloride to the 1, 3-cyclohexanedione to the Lewis acid is 1: 1-1.2: 3-3.5.

After the reaction is finished, dropwise adding water under an ice bath condition, and stirring at the temperature of 30-60 ℃ until the solid is completely dissolved.

Further, after the reaction is finished, water is dropwise added, the mixture is stirred at the temperature from room temperature to the reflux temperature until all solids are dissolved, the mixture is cooled to the room temperature, liquid and water phases are separated and extracted for 2 times by using an organic solvent, organic phases are combined, washed, dried and desolventized to obtain a crude product, the crude product is dissolved in a potassium hydroxide aqueous solution, one or more organic solvents are properly added, hydrochloric acid is used for adjusting the acidity, and the separated solids are filtered, washed and dried to obtain a mesotrione product. Alkali can be added into the water phase dissolved with the aluminum trichloride to generate aluminum hydroxide precipitate which is recycled.

The mesotrione herbicide includes mesotrione (mesotrione), sulcotrione (sulcotrione), tembotrione (tembotrione), topramezone (tefuryltrione), fenquinotrione, lancotrione, quintocetone, mequintocetone and quinclorac-clorac

The 2-nitro-4-methylsulfonylbenzoyl chloride used in the reaction can be prepared according to the method disclosed in CN105712912 and other starting materials or reagents are commercially available.

The invention has the advantages that:

according to the invention, 1, 3-cyclohexanedione and 2-nitro-4-methylsulfonylbenzoyl chloride are reacted to synthesize mesotrione under mild conditions by using Lewis acid, so that a large amount of dark viscous solid is not generated in the reaction process, and a large amount of acid gas is not discharged; and the post-treatment does not need to add a large amount of acid, and does not need the intermediate process of containing a cyanogen transposition agent and not processing enol ester; meanwhile, the method has the advantages of mild reaction, easy operation, less by-products, high conversion rate, high yield and high product purity.

Detailed Description

The following examples are presented to further illustrate embodiments of the present invention, and it should be understood that the embodiments described herein are for purposes of illustration and explanation only and are not intended to limit the invention.

Example 1

8.3g of aluminum trichloride (0.062mol) was placed in a 250mL three-necked flask (equipped with stirrer, thermometer and condenser), 80mL of 1, 2-dichloroethane was added and stirred, 5.27g (0.02mol) of 2-nitro-4-methylsulfonylbenzoyl chloride was added in an ice bath, after about 10 minutes the acid chloride had completely dissolved, 2.24g of 1, 3-cyclohexanedione (0.02mol) in 70mL of 1, 2-dichloroethane solution was added dropwise over about 15 minutes, the ice bath was removed, the reaction was carried out at room temperature for 1 hour, and the reaction was maintained at 40 ℃ for 4 hours. And (3) detecting the completion of the reaction by HPLC, cooling the reaction solution to room temperature, dropwise adding 50mL of water in an ice bath, stirring at 50 ℃ until the solid is completely dissolved, cooling, layering, separating out a water phase, extracting twice by using 80mL of 1, 2-dichloroethane, combining organic phases, washing by using 30mL of cold water, drying by using anhydrous magnesium sulfate, and desolventizing to obtain a crude product. Dissolving the crude product in 50mL of aqueous solution of 2.24g of potassium hydroxide, adjusting the pH value to about 1.5 by using hydrochloric acid, stirring for 1 hour at 55 +/-2 ℃, cooling, filtering the solid, washing by using cold water, and drying to obtain 6.35g of mesotrione product with the purity of 98.1% and the yield of about 91.9%.

Example 2

Adding 8.3g of aluminum trichloride (0.062mol) into a 250mL three-necked flask (with a stirring device, a thermometer and a condensing tube), adding 80mL of dichloromethane, stirring, adding 5.27g (0.02mol) of 2-nitro-4-methylsulfonylbenzoyl chloride under ice bath, completely dissolving the acyl chloride after about 10 minutes, dropwise adding 70mL of a dichloromethane solution of 2.24g of 1, 3-cyclohexanedione (0.02mol), completing dropwise adding for about 15 minutes, removing the ice bath, reacting at room temperature for 1 hour, and preserving the temperature at 35-40 ℃ for 4 hours. And (3) detecting the completion of the reaction by HPLC, cooling the reaction solution to room temperature, dropwise adding 50mL of water in an ice bath, stirring at 50 ℃ until the solid is completely dissolved, cooling, layering, separating out a water phase, extracting twice by using 80mL of dichloromethane, combining organic phases, washing by using 30mL of cold water, drying by using anhydrous magnesium sulfate, and desolventizing to obtain a crude product. Dissolving the crude product in 50mL of aqueous solution of 2.24g of potassium hydroxide, adjusting the pH value to about 1.5 by using hydrochloric acid, stirring for 1 hour at 55 +/-3 ℃, cooling, filtering the solid, washing by using cold water, and drying to obtain 6.45g of mesotrione product with the purity of 97.8% and the yield of about 93.0%.

Comparative example 1

8.3g of aluminum trichloride (0.062mol) were charged into a 250mL three-necked flask (equipped with stirrer, thermometer and condenser), 150mL of 1, 2-dichloroethane were added and stirred, and then 5.27g (0.02mol) of 2-nitro-4-methylsulfonylbenzoyl chloride was added and stirring was continued for 30 minutes. Then, 2.24g of 1, 3-cyclohexanedione (0.02mol) was added, and the reactor was heated to an internal reaction temperature of 58 ℃ to release gas in the system, and a viscous solid in the form of a lump appeared. Stirring for 3 hours, completing the reaction, cooling the reaction solution to room temperature, stirring and dropwise adding a solution of 28g of concentrated hydrochloric acid and 50mL of water in an ice bath, layering, extracting the water phase with 50mL of 1, 2-dichloroethane, combining the organic phases, and desolventizing to obtain a crude product. Adding 25 mL of methanol and 4 mL of 6 mol/L hydrochloric acid into the crude product, stirring for 1 hour at 60 +/-2 ℃, stirring overnight at room temperature, filtering the solid, dissolving the solid in 50mL of aqueous solution of 2.24g of potassium hydroxide, adjusting the pH value to about 1.5 by using the hydrochloric acid, cooling, filtering the solid, washing by using cold water, and drying to obtain the mesotrione product 4.30 with the purity of 96.5 percent and the yield of about 60.0 percent.

Comparative example 2

5.34g of aluminum trichloride (0.04mol) was charged into a 250mL three-necked flask with stirring, a thermometer and a condenser, 150mL of 1, 2-dichloroethane was added and stirred, and then 5.27g (0.02mol) of 2-nitro-4-methylsulfonylbenzoyl chloride was added and stirring was continued for 30 minutes. Then, 2.24g of 1, 3-cyclohexanedione (0.02mol) was added, and the reactor was heated to an internal reaction temperature of 58 ℃ and kept for a reaction time of 3 hours, and HPLC showed no formation of a product.