WO2022012482A1

WO2022012482A1 - Method for preparing mesotrione herbicide

Info

Publication number: WO2022012482A1
Application number: PCT/CN2021/105865
Authority: WO
Inventors: 吴鸿飞; 吴长春; 于海波; 徐靖博; 徐利保; 郭春晓; 程学明; 董燕; 孙宁宁
Original assignee: 沈阳中化农药化工研发有限公司; 江苏扬农化工股份有限公司
Priority date: 2020-07-17
Filing date: 2021-07-13
Publication date: 2022-01-20
Also published as: CN113943235A; CN113943235B

Abstract

The present invention belongs to the field of organic synthesis, and particularly relates to a method for preparing a mesotrione herbicide. 4-methanesulfonyl-2-nitrobenzoic acid is used as a raw material, and is subjected to a chloroformylation reaction and an esterification reaction to obtain a reaction system containing an enol ester, followed by a rearrangement reaction to prepare mesotrione, that is, a rearrangement catalyst is added into the reaction system containing the enol ester, same is maintained at 0-40ºC and subjected to the rearrangement reaction, so as to obtain mesotrione. According to the method of the present invention, the use of a highly toxic acetone cyanohydrin rearrangement catalyst is avoided, the reaction temperature is appropriate, the reaction time is short, the solvent can be recycled, the total yield of the prepared mesotrione herbicide product can reach 89%, the content is 98%, and the process is safe and environmentally-friendly, creates a small amount of the three wastes, and is suitable for industrial production.

Description

A kind of method for preparing mesotrione herbicide

technical field

The invention belongs to the field of organic synthesis, and in particular relates to a method for preparing mesotrione herbicide.

Background technique

Mesotrione (English generic mesotrione) is a triketone herbicide, which belongs to p-hydroxyphenylpyruvate dioxidase (HPPD) inhibitor.

EP 0186118 discloses a method for the transposition rearrangement of enol esters catalyzed by acetone cyanohydrin to acylated cyclic 1,3-diketone herbicidal compounds, ie triketone herbicidal compounds (including mesotrione).

US 4695673, US 5728889, US 10421714 etc. also disclose the method of translocation rearrangement from enol ester to triketone herbicidal compound under the action of acetone cyanohydrin rearrangement catalyst.

Since acetone cyanohydrin is a highly toxic chemical and poses a great risk to human, animal and environmental safety, it is urgent to study safer rearrangement catalysts to prepare mesotrione herbicide.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a method for preparing mesotrione herbicide.

For achieving the above object, technical scheme of the present invention is as follows:

A method for preparing mesotrione herbicide, using 4-methanesulfonyl-2-nitrobenzoic acid as a raw material to obtain a reaction system containing enol ester through acid chlorination reaction and esterification reaction, and then through rearrangement reaction to prepare To obtain mesotrione, a rearrangement catalyst is added to the reaction system containing the enol ester, and the rearrangement reaction is carried out at 0°C to 40°C under heat preservation to obtain mesotrione;

Among them, the rearrangement catalysts are rearrangement catalyst A and rearrangement catalyst B; rearrangement catalyst A is formamide, and rearrangement catalyst B is trifluoroacetic anhydride or trichloroacetyl chloride; rearrangement catalyst and 4-methanesulfonyl-2 - The molar ratio of nitrobenzoic acid is (0.12-4):1.

Among them, the rearrangement catalyst B is preferably trichloroacetyl chloride.

The molar ratio of the rearrangement catalyst A and the rearrangement catalyst B is 1:(1-3); the rearrangement reaction is carried out at a temperature of 0.5-8 hours.

The rearrangement reaction temperature of the reaction system containing the enol ester is 20°C-35°C, and the reaction is performed for 0.5-7 hours.

The rearrangement reaction temperature is 28°C-33°C, and the reaction time is 0.5-5 hours; wherein, the rearrangement catalyst A and the rearrangement catalyst B mole ratio is 1: (1-2); the rearrangement catalyst A and 4- The molar ratio of methanesulfonyl-2-nitrobenzoic acid is (0.08-1):1.

The rearrangement reaction temperature is 30°C-33°C, and the reaction time is 0.5-4 hours; wherein, the mole ratio of the rearrangement catalyst A to 4-methanesulfonyl-2-nitrobenzoic acid is (0.1-1):1 .

The esterification reaction is finished, namely, the rearrangement catalyst A and the rearrangement catalyst B are added to the reaction system containing the enol ester, and then the temperature is raised to the rearrangement reaction temperature to react, and the reaction is adjusted with a 10% aqueous potassium hydroxide solution after the reaction is completed. The pH value of the system is alkaline, then it is lowered to room temperature to stand for extraction and stratification, the water phase is collected, the pH value of the water phase feed liquid is adjusted to 2-3 with 10% hydrochloric acid aqueous solution, filtered, and the filter cake is washed with water to obtain mesotrione herbicide.

The reaction system containing the enol ester is added to the product 4-methanesulfonyl-2-nitrobenzoyl chloride obtained after the acid chlorination reaction using 4-methanesulfonyl-2-nitrobenzoic acid as a raw material. solvent, then add 1,3-cyclohexanedione, drop an organic base at 2-6° C., and continue the incubation reaction for 0.5-1 hour after the dropwise addition to obtain a reaction solution of the esterification reaction product enol ester.

The solvent is toluene or 1,2-dichloroethane; the organic base trimethylamine, triethylamine, diisopropylethylamine, pyridine or 4-dimethylaminopyridine;

The product 4-methanesulfonyl-2-nitrobenzoyl chloride, solvent, 1,3-cyclohexanedione and 4-methylsulfonyl-2-nitrobenzoyl chloride obtained after acid chlorination reaction with 4-methanesulfonyl-2-nitrobenzoic acid as raw material and The molar ratio between organic bases is 1:(10-30):(0.9-1.1):(1.5-5).

The raw material 4-methanesulfonyl-2-nitrobenzoic acid is added to the solvent, the temperature is raised to 45-50° C., thionyl chloride is added dropwise, and the reflux reaction is continued for 2-2.5 hours after the dropwise addition, and then evaporated under reduced pressure. Solvent and excess thionyl chloride gave 4-methanesulfonyl-2-nitrobenzoyl chloride.

The molar ratio of the thionyl chloride to the raw material 4-methanesulfonyl-2-nitrobenzoic acid is (1-2):1.

Further, the method for preparing mesotrione herbicide, the reaction formula is as follows,

1) Acyl chloride reaction formula

2) Acylation reaction formula

3) rearrangement reaction

1) Acyl chloride reaction

Dissolve 4-methanesulfonyl-2-nitrobenzoic acid in solvent toluene or 1,2-dichloroethane, heat up to 45-50°C, add thionyl chloride dropwise, and continue to reflux reaction 2- After 2.5 hours, the solvent and excess thionyl chloride were distilled off under reduced pressure to obtain 4-methanesulfonyl-2-nitrobenzoyl chloride. The solvent is preferably 1,2-dichloroethane.

2) Acylation reaction

To the product of step 1), namely 4-methanesulfonyl-2-nitrobenzoyl chloride, add solvent toluene or 1,2-dichloroethane, then add 1,3-cyclohexanedione, and at 2-6 Between ℃, organic base trimethylamine, triethylamine, diisopropylethylamine, pyridine or 4-dimethylaminopyridine are added dropwise, and after the dropwise addition, the incubation reaction is continued for 0.5-1 hour to obtain the enol ester, namely (3- Oxocyclohex-1-en-1-yl)4-methanesulfonyl-2-nitrobenzoate. The solvent is preferably 1,2-dichloroethane; the organic base is preferably selected from trimethylamine, triethylamine, diisopropylethylamine, and more preferably triethylamine.

3) rearrangement reaction

To the reaction solution after the esterification reaction in step 2) (that is, the reaction system containing the enol ester), the rearrangement catalyst A and the rearrangement catalyst B are added, and the reaction is kept at 0°C-40°C for 0.5-8 hours, that is, Got mesotrione.

Compared with the prior art, the advantages of the present invention are:

The rearrangement catalyst in the present invention overcomes the risk brought by acetone cyanohydrin, which is highly toxic, and under specific conditions, the rearrangement agent is compounded, and the same mole number of rearrangement and translocation catalyst is used, which is similar to the prior art acetone cyanohydrin. The reaction conditions are mild, the conversion efficiency is high, the yield is higher, and the obtained product content is higher. Using the catalyst of the present invention is safer and more environmentally friendly. The completion of the present invention provides an effective preparation method for the industrial production of mesotrione herbicide.

detailed description

The following example results are used to further illustrate the present invention, but are not meant to limit the present invention.

In each example, raw materials and reagents such as 4-methanesulfonyl-2-nitrobenzoic acid, 1,3-cyclohexanedione, and triethylamine can be purchased from commercially available products.

Example 1

1) the preparation of acid chloride reaction 4-methanesulfonyl-2-nitrobenzoyl chloride:

4-Methanesulfonyl-2-nitrobenzoic acid (14.91g, 0.06mol), DMF (0.25g) and 1,2-dichloroethane (100g) were added to the dry reaction flask, and the temperature was raised to 45°C with stirring , thionyl chloride (10.83g, 0.09mol) was added dropwise, and the reaction was performed at reflux temperature for 2 hours after dropping, and the solvent and excess thionyl chloride were evaporated under reduced pressure to obtain 4-methanesulfonyl-2-nitrobenzyl Acid chloride 16.04g.

2) Preparation of acylation reaction (3-oxocyclohex-1-en-1-yl)-4-methanesulfonyl-2-nitrobenzoate:

1,2-Dichloroethane (150g) and 1,3-cyclohexanedione (7.21g, 0.063mol) were added to the 4-methanesulfonyl-2-nitrobenzoyl chloride obtained above, and the temperature was controlled at Triethylamine (18.40g, 0.18mol) was added dropwise at 2-6°C for 1.5-2 hours, and the temperature was kept at 2-6°C for 0.5 hours to obtain the intermediate (3-oxocyclohex-1-ene-1- yl)-4-methanesulfonyl-2-nitrobenzoate.

3) Preparation of rearrangement reaction 2-(4-methanesulfonyl-2-nitrobenzoyl)-1,3-cyclohexanedione (mesotrione):

The rearrangement catalyst formamide (0.54 g, 11.9 mmol) and trifluoroacetic anhydride (2.54 g, 12.0 mmol) were sequentially added to the above reaction solution, and the temperature was raised to 30-32° C. for 4 hours. Water (80g) was added, 10% potassium hydroxide solution was added dropwise to pH=10～11, stirred at room temperature for 0.5 hours, left to stand, layered, the lower organic phase was collected, and the upper feed liquid was added with 1,2-dichloroethane to extract Once, combine the organic phase to be recovered solvent and triethylamine, add 10% hydrochloric acid to the upper layer to acidify to pH=2～3, stir at room temperature for 2 hours, filter, wash the filter cake twice with water and discharge to obtain a light yellow wet product 20.82 g, drying at 40-45° C. to obtain 18.32 g of mesotrione technical product, quantitative content of 98.0%, and yield of 88.1% (calculated as 4-methanesulfonyl-2-nitrobenzoic acid).

Example 2

4-Methanesulfonyl-2-nitrobenzoic acid (14.90g, 0.06mol), DMF (0.25g) and 1,2-dichloroethane (100g) were added to the dry reaction flask, and the temperature was raised to 48°C with stirring , thionyl chloride (9.41g, 0.078mol) was added dropwise, and the reaction was performed at reflux temperature for 2 hours after dropping, and the solvent and excess thionyl chloride were evaporated under reduced pressure to obtain 4-methanesulfonyl-2-nitrobenzyl Acid chloride 15.92g.

1,2-Dichloroethane (150g) and 1,3-cyclohexanedione (7.22g, 0.063mol) were added to the 4-methanesulfonyl-2-nitrobenzoyl chloride obtained above, and the temperature was controlled at Triethylamine (18.41g, 0.18mol) was added dropwise at 2-6°C for 1.5-2 hours, and the temperature was kept at 2-6°C for 0.5 hours to obtain the intermediate (3-oxocyclohex-1-ene-1- yl)-4-methanesulfonyl-2-nitrobenzoate.

The rearrangement catalyst formamide (0.54 g, 11.9 mmol) and trichloroacetyl chloride (2.21 g, 12.0 mmol) were sequentially added to the above reaction solution, and the temperature was raised to 30-33°C for 4 hours. Water (80g) was added, 10% potassium hydroxide solution was added dropwise to pH=10～11, stirred at room temperature for 0.5 hours, left to stand, layered, the lower organic phase was collected, and the upper feed liquid was added with 1,2-dichloroethane to extract Once, combine the organic phase to be recovered solvent and triethylamine, add 10% hydrochloric acid to the upper layer of feed liquid to acidify to pH=2～3, stir at room temperature for 2 hours, filter, wash the filter cake twice with water and discharge to obtain light yellow wet product 21.03 g, drying at 40-45 DEG C to obtain 18.53 g of mesotrione technical product, quantitative content 98.2%, yield 89.2% (calculated as 4-methanesulfonyl-2-nitrobenzoic acid).

Example 3

4-Methanesulfonyl-2-nitrobenzoic acid (14.92g, 0.06mol), DMF (0.25g) and toluene (100g) were added to the dry reaction flask, the temperature was raised to 50°C with stirring, and thionyl chloride was added dropwise. (9.43 g, 0.078 mol), react at reflux temperature for 2 hours after dropping, and evaporate the solvent and excess thionyl chloride under reduced pressure to obtain 16.13 g of 4-methanesulfonyl-2-nitrobenzoyl chloride.

To the 4-methanesulfonyl-2-nitrobenzoyl chloride obtained above, 1,2-dichloroethane (150g) and 1,3-cyclohexanedione (7.20g, 0.063mol) were added, and the temperature was controlled at Triethylamine (18.42g, 0.18mol) was added dropwise at 2-6°C for 1.5-2 hours, and the temperature was kept at 2-6°C for 0.5 hours to obtain the intermediate (3-oxocyclohex-1-ene-1- yl)-4-methanesulfonyl-2-nitrobenzoate.

The rearrangement catalyst formamide (0.28 g, 6.1 mmol) and trichloroacetyl chloride (1.11 g, 6.0 mmol) were sequentially added to the above reaction solution, and the temperature was raised to 30-33° C. for 6 hours. Water (80g) was added, 10% potassium hydroxide solution was added dropwise to pH=10～11, stirred at room temperature for 0.5 hours, left to stand, layered, the lower organic phase was collected, and the upper feed liquid was added with 1,2-dichloroethane to extract Once, combine the organic phase to be recovered solvent and triethylamine, add 10% hydrochloric acid to the upper layer of feed liquid to acidify to pH=2～3, stir at room temperature for 2 hours, filter, wash the filter cake twice with water and discharge to obtain light yellow wet product 20.73 g, drying at 40-45° C. to obtain 18.42 g of mesotrione technical product, quantitative content of 97.6%, and yield of 88.2% (calculated as 4-methanesulfonyl-2-nitrobenzoic acid).

Example 4

4-Methanesulfonyl-2-nitrobenzoic acid (14.91g, 0.06mol), DMF (0.25g) and toluene (100g) were added to the dry reaction flask, the temperature was raised to 50°C with stirring, and thionyl chloride was added dropwise. (9.43 g, 0.078 mol), react at reflux temperature for 2 hours after dropping, and evaporate the solvent and excess thionyl chloride under reduced pressure to obtain 16.24 g of 4-methanesulfonyl-2-nitrobenzoyl chloride.

The rearrangement catalyst formamide (0.41 g, 9.0 mmol) and trichloroacetyl chloride (1.65 g, 9.0 mmol) were sequentially added to the above reaction solution, and the temperature was raised to 30-33° C. for 4 hours. Water (80g) was added, 10% potassium hydroxide solution was added dropwise to pH=10～11, stirred at room temperature for 0.5 hours, left to stand, layered, the lower organic phase was collected, and the upper feed liquid was added with 1,2-dichloroethane to extract Once, combine the organic phase to be recovered solvent and triethylamine, add 10% hydrochloric acid to the upper layer to acidify to pH=2～3, stir at room temperature for 2 hours, filter, wash the filter cake twice with water and discharge to obtain light yellow wet product 20.62 g, drying at 40-45° C. to obtain 18.51 g of mesotrione technical product, quantitative content of 98.1%, and yield of 89.1% (calculated as 4-methanesulfonyl-2-nitrobenzoic acid).

Example 5

According to the method of Example 2, in the process of step 3), the rearrangement catalyst formamide (0.14g, 3.0mmol) and trichloroacetyl chloride (0.55g, 3.0mmol) were added successively, and other conditions remained unchanged to obtain the mesotrione The quantitative content was 94.3%, and the yield was 74.5% (calculated as 4-methanesulfonyl-2-nitrobenzoic acid).

Example 6

According to the method of Example 2, trichloroacetyl chloride (0.55 g, 3.0 mmol) was added in the process of step 3), and other conditions were unchanged, and the quantitative content of mesotrione was 94.1%, and the yield was 74.0% (with 4-methylmethane). sulfonyl-2-nitrobenzoic acid).

Example 7

According to the method of Example 2, triethylamine (0.57g, 0.084mol) was added dropwise in the process of step 3), and other conditions were unchanged, the quantitative content of mesotrione was 90.4%, and the yield was 67.9% (with 4-methylmethane). sulfonyl-2-nitrobenzoic acid).

Example 8

According to the method of Example 2, in step 3) the rearrangement reaction was carried out at 45-50 ° C for 4 hours, and other conditions remained unchanged to obtain a quantitative content of mesotrione of 92.4% and a yield of 76.2% (with 4-methanesulfonyl- 2-nitrobenzoic acid).

It can be seen from the above-mentioned examples 5, 6, 7 and 8 that the rearrangement catalyst is in a certain amount of addition in the preparation process, and the two rearrangement catalysts are in a suitable dosage ratio, and the rearrangement reaction is carried out under the preferred conditions simultaneously. It is beneficial to increase the yield and content.

Example 9

According to the method of Example 2, only the rearrangement catalyst formamide (0.54 g, 11.9 mmol) was added, and the rearrangement catalyst trichloroacetyl chloride was not added, and mesotrione could not be obtained.

Example 10

According to the method of Example 2, only the rearrangement catalyst trichloroacetyl chloride (2.21 g, 12.0 mmol) was added, and the rearrangement catalyst formamide was not added to obtain mesotrione.

Example 11

According to the method of Example 1, only the rearrangement catalyst trifluoroacetic anhydride (2.54 g, 12.0 mmol) was added, and the rearrangement catalyst formamide was not added, and mesotrione could not be obtained.

From the above-mentioned Examples 8, 9 and 2; Examples 10 and 1, it can be seen that the rearrangement catalyst formamide and the rearrangement catalyst trichloroacetyl chloride of the present invention need to be used at the same time and can play an efficient rearrangement within the preferred ratio range. Catalysis, using either of the two alone cannot play a role in rearranging and catalyzing the reaction.

Comparative Example 1

According to the method of Example 2, the rearrangement catalyst formamide and trichloroacetyl chloride were replaced with acetone cyanohydrin (0.52 g, 6.0 mmol) to obtain a quantitative content of mesotrione of 95.8% and a yield of 85.5% (with 4-methyl cyanohydrin). sulfonyl-2-nitrobenzoic acid).

Comparative Example 2

According to the method of Example 2, the rearrangement catalyst formamide and trichloroacetyl chloride were replaced with acetone cyanohydrin (1.03 g, 12.0 mmol) to obtain a quantitative content of mesotrione of 97.0% and a yield of 86.2% (with 4-methylmethane). sulfonyl-2-nitrobenzoic acid).

Comparative Example 3

According to the method of Example 2, the rearrangement catalyst formamide and trichloroacetyl chloride were replaced with acetone cyanohydrin (2.06 g, 24.0 mmol) to obtain a quantitative content of mesotrione of 96.8% and a yield of 86.5% (with 4-methylmethane). sulfonyl-2-nitrobenzoic acid).

It can be seen from the above examples that the specific rearrangement catalyst of the present invention is used, and the same mole number is used under a certain amount of addition, so that the conversion efficiency is high, the yield is high, and the obtained product content is higher; meanwhile, the present invention uses rearrangement. The catalyst is safe and environmentally friendly.

Claims

A method for preparing mesotrione herbicide, using 4-methanesulfonyl-2-nitrobenzoic acid as a raw material to obtain a reaction system containing enol ester through acid chlorination reaction and esterification reaction, and then through rearrangement reaction to prepare To obtain mesotrione, it is characterized in that: a rearrangement catalyst is added to the reaction system containing the enol ester, and the rearrangement reaction is carried out at a temperature of 0°C to 40°C under heat preservation to obtain mesotrione;

Among them, the rearrangement catalysts are rearrangement catalyst A and rearrangement catalyst B; rearrangement catalyst A is formamide, and rearrangement catalyst B is trifluoroacetic anhydride or trichloroacetyl chloride; rearrangement catalyst and 4-methanesulfonyl-2 - The molar ratio of nitrobenzoic acid is (0.12-4):1.
According to the method for preparing mesotrione herbicide according to claim 1, it is characterized in that: the mol ratio of described rearrangement catalyst A and rearrangement catalyst B is 1:(1-3); 8 hours.
The method for preparing mesotrione herbicide according to claim 1 or 2, wherein the reaction system rearrangement reaction temperature of the enol ester-containing reaction system is 20°C-35°C, and the reaction is performed for 0.5-7 hours.
The method for preparing mesotrione herbicide according to claim 3, characterized in that: the rearrangement reaction temperature is 28°C-33°C, and the reaction time is 0.5-5 hours; The molar ratio of the rearrangement catalyst B is 1:(1-2); the molar ratio of the rearrangement catalyst A to 4-methanesulfonyl-2-nitrobenzoic acid is (0.08-1):1.
The method for preparing mesotrione herbicide according to claim 4, wherein the rearrangement reaction temperature is 30°C-33°C, and the reaction time is 0.5-4 hours; wherein, the rearrangement catalysts A and 4 -Methylsulfonyl-2-nitrobenzoic acid in a molar ratio of (0.1-1):1.
According to the method for preparing mesotrione herbicide according to claim 1 or 2, it is characterized in that: the end of the esterification reaction is to add rearrangement catalyst A and rearrangement catalyst B to the reaction system containing the enol ester , then heat up to the rearrangement reaction temperature to react, after the reaction, adjust the pH value of the system to alkaline with 10% potassium hydroxide aqueous solution, drop to room temperature and stand for extraction and stratification, collect the water phase, and use 10% aqueous solution for the water phase. The aqueous hydrochloric acid solution is adjusted to pH 2-3, filtered, and the filter cake is washed with water to obtain the mesotrione herbicide.
According to the method for preparing mesotrione herbicide according to claim 1, it is characterized in that: the reaction system containing enol ester is to take 4-methanesulfonyl-2-nitrobenzoic acid as raw material through acyl chloride Add solvent to the product 4-methylsulfonyl-2-nitrobenzoyl chloride obtained after the reaction, then add 1,3-cyclohexanedione, add organic base dropwise at 2-6°C, and continue after the dropwise addition The reaction is incubated for 0.5-1 hour to obtain the reaction solution of the enol ester of the esterification reaction product.
The method for preparing mesotrione herbicide according to claim 7, characterized in that: the solvent is toluene or 1,2-dichloroethane; the organic bases trimethylamine, triethylamine, diisopropyl ethylamine, pyridine or 4-dimethylaminopyridine;

The product 4-methanesulfonyl-2-nitrobenzoyl chloride, solvent, 1,3-cyclohexanedione and 4-methylsulfonyl-2-nitrobenzoyl chloride obtained after acid chlorination reaction with 4-methanesulfonyl-2-nitrobenzoic acid as raw material and The molar ratio between organic bases is 1:(10-30):(0.9-1.1):(1.5-5).
The method for preparing mesotrione herbicide according to claim 1 or 7, characterized in that: the raw material 4-methanesulfonyl-2-nitrobenzoic acid is added to the solvent, and the temperature is raised to 45-50° C. , add thionyl chloride dropwise, continue to reflux for 2-2.5 hours after the dropwise addition, evaporate the solvent and excess thionyl chloride under reduced pressure to obtain 4-methanesulfonyl-2-nitrobenzoyl chloride.
According to the method for preparing mesotrione herbicide according to claim 9, it is characterized in that: the mol ratio of described sulfur oxychloride and raw material 4-methylsulfonyl-2-nitrobenzoic acid is (1-2) :1.