CN113024479B - Preparation method of clomazone - Google Patents

Abstract

The present invention relates to a preparation method of clomazone. The invention provides hydroxylamine hydrochloride as a raw material, and under the action of a self-made ether catalyst, chloropivaloyl chloride is added dropwise to obtain an intermediate 3-chloro-N-hydroxy-2,2-dimethylpropionamide in high yield, and then 4,4-dimethyl-3-isoxazolone prepared by cyclization can be directly benzylated under the catalysis of flake base to obtain 2-(2-chlorophenyl)methyl-4 without separation, 4-Dimethyl-3-isoxazolone. Compared with the method in the existing literature, the method of the present invention uses the self-made ether catalyst innovatively, so that the yield of the first step is significantly improved, and the content and optical purity of the product are high. In the last step of the benzylation reaction, flake base is used in order to improve the yield, and water is used as a solvent throughout the reaction, which has low cost, simple recovery and post-treatment, mild reaction and simple intermediate control. The preparation method of the invention has the advantages of easy-to-obtain reaction raw materials, mild reaction, high yield, simple separation and purification, low cost and environment-friendly preparation process.

Description

A kind of preparation method of clomazone

technical field

The invention relates to a new method for preparing a pigment-inhibiting preemergence herbicide clomazone, and relates to the fields of oximation, ring closure, condensation and the like.

Background technique

Clomazone is a highly effective, low toxicity, isoxazolone selective pre-emergence herbicide, mainly used for controlling broadleaf weeds and grass weeds in soybean fields, and can also be used for cassava, corn, rape, sugarcane and Weed control in tobacco fields. The main mechanism of action of clomazone is to inhibit the biosynthesis of carotene and chlorophyll by inhibiting the synthesis of isoprene compounds. The preparation method of current bibliographical report generally has the following several: o-chlorobenzaldehyde method mainly takes o-chlorobenzaldehyde as starting material, at first o-chlorobenzaldehyde and salt

Acid hydroxylamine reacts to generate oxime, and then the oxime is reduced to obtain o-chlorobenzyl hydroxylamine, and o-chlorobenzyl hydroxylamine reacts with 3-chloro-2,2-dimethylpropionyl chloride to obtain 3-chloro-N-(2-chloro- benzyl)-N-hydroxy-2,2-dimethylpropionamide, then 3-chloro-N-(2-chlorobenzyl)-N-hydroxy-2,2-dimethylpropionamide in the role of bases The ring was closed to obtain 2-(2-chlorophenyl)methyl-4,4-dimethyl-3-isoxazolone.

In this method, the reduction reaction of o-chlorobenzaldehyde oxime is difficult to control the product in the hydroxylamine stage, and the yield can only reach 80%. Moreover, a large amount of solvent is used, the product purification process is complicated, the reducing agent is expensive, and the synthetic route has high cost, so industrial production cannot be realized.

Another synthetic method is the chloropivaloyl chloride method, which uses 3-chloro-2,2-dimethylpropionyl chloride or 3-bromo-2,2-dimethylpropionyl chloride as raw materials, and undergoes ammonolysis and cyclization. and benzylation to finally complete the synthesis of 2-(2-chlorophenyl)methyl-4,4-dimethyl-3-isoxazolone. The main feature of this route is that there are fewer reaction steps and milder reaction conditions. , the operation is simple, the raw materials are easily obtained, the yield is relatively high, and the method has great advantages over the o-chlorobenzaldehyde method, and is more suitable for industrial production. Liu Weidong, Tang Dexiu and others have proposed improvements to the above method, but generally the yield is not high when synthesizing 3-chloro-N-hydroxy-2,2-dimethylpropionamide, resulting in a small increase in the final reaction yield. The processing steps are cumbersome and not suitable for industrial production.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a method suitable for industrialized preparation of clomazone, which is simple, low-cost, and environment-friendly. Comprise the following steps: a kind of preparation method of clomazone, is characterized in that, carry out according to following processing steps:

1) 3-Chloro-2,2-dimethylpropionyl chloride is used as the starting material, and the intermediate product 3-Chloro-N-hydroxy-2,2-dimethylpropionamide is first generated through the aminolysis reaction, which is synthesized in the intermediate In the process, an ether catalyst is adopted in the synthesis process, and the ether catalyst is a mixture of a cyclic ether and a crown ether:

；

;

2) Then the intermediate undergoes cyclization to generate 4,4-dimethyl-3-isoxazolone benzylation to generate the target product 2-(2-chlorophenyl)methyl-4,4-dimethyl -3-isoxazolone;

Further, the cyclic ether is tetrahydrofuran, the crown ether is 18-crown-6-ether, and the molar ratio of the tetrahydrofuran and 18-crown-6-ether is 1:0.1-0.3.

Further, in the preparation method of the ether catalyst, firstly, 1/3-2/3 of the tetrahydrofuran is input into the reactor, then the 18-crown-6-ether is added, and then the remaining tetrahydrofuran is added to the reactor Inside, stirring while adding.

Further, the benzylation reaction uses flake base as a catalyst.

The advantages of the present invention are as follows: the present invention provides a reaction system completely using water as a solvent, using hydroxylamine hydrochloride as a raw material, and under the action of a self-made ether catalyst, chloropivaloyl chloride is added dropwise, and the intermediate 3- Chloro-N-hydroxy-2,2-dimethylpropionamide, then 4,4-dimethyl-3-isoxazolone prepared by cyclization, without isolation directly under the catalysis of our pioneering flake base catalyzed benzyl The obtained 2-(2-chlorophenyl) methyl-4,4-dimethyl-3-isoxazolone. Compared with the method in the existing literature, the method of the present invention uses the self-made ether catalyst innovatively, so that the yield of the first step is significantly improved, and the content and optical purity of the product are high. In the last step of the benzylation reaction, flake base is used in order to improve the yield, and water is used as a solvent throughout the reaction, which has low cost, simple recovery and post-treatment, mild reaction and simple intermediate control. To sum up, the preparation method of the present invention has the advantages of easy-to-obtain reaction raw materials, mild reaction, high yield, simple separation and purification, low cost and environment-friendly preparation process, and has a good prospect of industrial application.

Detailed ways

Example one:

Step 1 Add 18.8g (0.26mol) hydroxylamine hydrochloride and 100ml distilled water in 250ml four-necked flask, 2g self-made ether catalyst, described crown ether is 18-crown-6-ether, described tetrahydrofuran and 18-crown-6 -The molar ratio of ether is 1:0.2; stir under an ice-salt bath (-5～0℃), and add 30% NaOH solution dropwise to make the pH value of the solution reach 7.2. Then 6ml (0.2mol) of chloropivaloyl chloride was added dropwise, and 30% NaOH solution was added dropwise at the same time to keep the pH of the system at 7.2±0.1. The dropwise addition was completed within 1.5h, and the mixture was stirred at room temperature for 3h. After the reaction, filtered and dried to obtain a white solid, which was 3-chloro-N-hydroxy-2,2-dimethylpropanamide. Content 99.0% (HPLC), yield 95.3%.

Step 2:

To a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer and a mechanical stirring device, add 15.2g of 3-chloro-N-hydroxy-2,2-dimethylpropanamide (from the first step) and 55ml of distilled water, stirring vigorously at 45°C. 30% NaOH solution was added dropwise until the solid was completely dissolved, and the pH was 8.2. Continue to add 30% NaOH solution dropwise to pH 9.0, and continue to stir at this temperature for 3 hours, during which time, pay attention to adding lye to maintain pH 9.0 ± 0.1. Then, 0.6 g of NaOH solid was added, and the reaction was kept at 20 °C for 18 h to obtain a 4,4-dimethylisoxazol-3-one reaction solution. The reaction solution does not need to be separated and can be directly used in the next reaction. Content 97.2% (HPLC).

The reaction solution (containing 97.2% 4,4-dimethylisoxazol-3-one) after ring closure in the previous step was heated to 90 °C, 0.6 g of NaOH solid was added, and 0.4 g of tetrabutylammonium bromide was used as a catalyst, 16.1g of o-chlorobenzyl chloride was added dropwise, and the addition was completed within 0.5h. The reaction was incubated at 90°C for 5h. After the reaction was completed, it was cooled to room temperature, extracted three times with 30 ml of ethyl acetate, and the solvent was removed from the oil phase to obtain a pale yellow oil, which was the crude clomazone. The yield was 94%, and the total yield was 87.1%.

Example two:

Step 1 Add 18.8g (0.26mol) hydroxylamine hydrochloride and 100ml distilled water in 250ml four-necked flask, 2g self-made ether catalyst, described crown ether is 18-crown-6-ether, described tetrahydrofuran and 18-crown-6 -The molar ratio of ether is 1:0.17; stir under an ice-salt bath (-5～0℃), and add 50% NaOH solution dropwise to make the pH value of the solution reach 7.2. Then, 6 ml (0.2 mol) of chloropivaloyl chloride was added dropwise, and 50% NaOH solution was added dropwise at the same time to keep the pH of the system at 7.2±0.1. The dropwise addition was completed within 1.5 h, and the mixture was stirred at room temperature for 3 h. After the reaction, filtered and dried to obtain a white solid, which was 3-chloro-N-hydroxy-2,2-dimethylpropanamide. Content 99.0% (HPLC), yield 93.3%.

Step 2:

To a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer and a mechanical stirring device, add 15.2g of 3-chloro-N-hydroxy-2,2-dimethylpropanamide (from the first step) and 55ml of distilled water, stirring vigorously at 45°C. 30% NaOH solution was added dropwise until the solid was completely dissolved, and the pH was 8.2. Continue to add 50% NaOH solution dropwise to pH 9.0, and continue to stir at this temperature for 3 hours, during which time, pay attention to adding lye to maintain pH 9.0 ± 0.1. Then, 0.6 g of NaOH solid was added, and the reaction was kept at 20 °C for 20 h to obtain a 4,4-dimethylisoxazol-3-one reaction solution. The reaction solution does not need to be separated and can be directly used in the next reaction. Content 98.2% (HPLC).

The reaction solution (containing 97.2% 4,4-dimethylisoxazol-3-one) after ring closure in the previous step was heated to 90 °C, 0.6 g of NaOH solid was added, and 0.4 g of tetrabutylammonium bromide was used as a catalyst, 16.1g of o-chlorobenzyl chloride was added dropwise, and the addition was completed within 1h. The reaction was incubated at 90°C for 5h. After the reaction was completed, it was cooled to room temperature, extracted three times with 30 ml of ethyl acetate, and the solvent was removed from the oil phase to obtain a pale yellow oil, which was the crude clomazone. The yield was 89%, and the total yield was 82.7%.

Example three:

Step 1 Add 18.8g (0.26mol) hydroxylamine hydrochloride and 100ml distilled water in 250ml four-necked flask, 2g self-made ether catalyst, described crown ether is 18-crown-6-ether, described tetrahydrofuran and 18-crown-6 -The molar ratio of ether is 1:0.26; stir under an ice-salt bath (-5～0℃), and add 30% KOH solution dropwise to make the pH value of the solution reach 7.2. Then, 6 ml (0.2 mol) of chloropivaloyl chloride was added dropwise, and 30% KOH solution was added dropwise at the same time to maintain the pH of the system at 7.2±0.1. The dropwise addition was completed within 1.5 h, and the mixture was stirred at room temperature for 3 h. After the reaction, filtered and dried to obtain a white solid, which was 3-chloro-N-hydroxy-2,2-dimethylpropanamide. Content 99.0% (HPLC), yield 94.3%.

Step 2:

To a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer and a mechanical stirring device, add 15.2g of 3-chloro-N-hydroxy-2,2-dimethylpropanamide (from the first step) and 55ml of distilled water, stirring vigorously at 45°C. 30% NaOH solution was added dropwise until the solid was completely dissolved, and the pH was 8.2. Continue to add 30% KOH solution dropwise to pH 9.0, and continue to stir at this temperature for 3 hours, during which time, pay attention to adding lye to maintain pH 9.0 ± 0.1. Then, 0.6 g of NaOH solid was added, and the reaction was kept at 20 °C for 18 h to obtain a 4,4-dimethylisoxazol-3-one reaction solution. The reaction solution does not need to be separated and can be directly used in the next reaction. Content 98.2% (HPLC).

The reaction solution (containing 97.2% 4,4-dimethylisoxazol-3-one) after ring closure in the previous step was heated to 90 °C, 0.6 g of NaOH solid was added, and 0.4 g of tetrabutylammonium bromide was used as a catalyst, 16.1g of o-chlorobenzyl chloride was added dropwise, and the addition was completed within 1.5h. The reaction was incubated at 90°C for 5h. After the reaction was completed, it was cooled to room temperature, extracted three times with 30 ml of ethyl acetate, and the solvent was removed from the oil phase to obtain a pale yellow oil, which was the crude clomazone. The yield was 80%, and the total yield was 75.4%.

Example 4 (comparative example):

Step 1: Add 18.8g (0.26mol) hydroxylamine hydrochloride and 100ml distilled water to a 250ml four-necked flask, stir in an ice-salt bath (-5～0℃), and add 30% NaOH solution dropwise to make the pH value of the solution reach 7.2. Then, 7.8 ml (0.26 mol) of chloropivaloyl chloride was added dropwise, and 30% NaOH solution was added dropwise at the same time to keep the pH of the system at 7.2±0.1. The dropwise addition was completed within 1.5 h, and the mixture was stirred at room temperature for 3 h. After the reaction, filtered and dried to obtain a white solid, which was 3-chloro-N-hydroxy-2,2-dimethylpropanamide. Content 85.0% (HPLC), yield 76.7%.

Step 2:

To a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer and a mechanical stirring device, add 15.2g of 3-chloro-N-hydroxy-2,2-dimethylpropanamide (from the first step) and 55ml of distilled water, stirring vigorously at 45°C. 30% NaOH solution was added dropwise until the solid was completely dissolved, and the pH was 8.2. Continue to add 30% NaOH solution dropwise to pH 9.0, and continue to stir at this temperature for 3 hours, during which time, pay attention to adding lye to maintain pH 9.0 ± 0.1. Then, 0.6 g of NaOH solid was added, and the reaction was kept at 20 °C for 18 h to obtain a 4,4-dimethylisoxazol-3-one reaction solution. The reaction solution does not need to be separated and can be directly used in the next reaction, with a content of 88.6% (HPLC).

The reaction solution (containing 97.2% 4,4-dimethylisoxazol-3-one) after ring closure in the previous step was heated to 100 °C, 0.6 g of NaOH solid was added, and 0.4 g of tetrabutylammonium bromide was used as a catalyst, 16.1g of o-chlorobenzyl chloride was added dropwise, and the addition was completed within 0.5h. The reaction was incubated at 90°C for 5h. After the reaction was completed, it was cooled to room temperature, extracted three times with 30 ml of ethyl acetate, and the solvent was removed from the oil phase to obtain a light yellow oily product, which was a crude clomazone product with a yield of 81.2% and a total yield of 69.5%.

Claims (3)

1. The preparation method of clomazone is characterized by comprising the following steps of:

1) 3-chloro-2, 2-dimethylpropionyl chloride is used as a starting material, an intermediate product 3-chloro-N-hydroxy-2, 2-dimethylpropionamide is firstly generated through ammonolysis reaction, and in the synthesis process of the intermediate, an ether catalyst is adopted, wherein the ether catalyst is a mixture of cyclic ether and crown ether:

；

2) then the intermediate is subjected to cyclization reaction to generate 4, 4-dimethyl-3-isoxazolidone, and the target product 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone is generated through benzylation reaction;

；

the cyclic ether is tetrahydrofuran, the crown ether is 18-crown-6-ether, and the molar ratio of the tetrahydrofuran to the 18-crown-6-ether is 1: 0.1-0.3.

2. The method of claim 1, wherein the ether catalyst is prepared by introducing 1/3-2/3-tetrahydrofuran into a reactor, adding 18-crown-6-ether, and adding the rest tetrahydrofuran into the reactor while stirring.

3. The method of claim 1, wherein the benzylation reaction is carried out using caustic soda flakes as a catalyst.