CN113024479A

CN113024479A - Preparation method of clomazone

Info

Publication number: CN113024479A
Application number: CN201911344799.5A
Authority: CN
Inventors: 于国权; 孙霞林; 马长庆; 丁华平
Original assignee: Jiangsu Changqing Agrochemical Co ltd
Current assignee: Jiangsu Changqing Agrochemical Co ltd
Priority date: 2019-12-24
Filing date: 2019-12-24
Publication date: 2021-06-25
Anticipated expiration: 2039-12-24
Also published as: CN113024479B

Abstract

本发明涉及一种异噁草松的制备方法。本发明提供了以盐酸羟胺为原料，在自制醚类催化剂作用下，滴加氯代特戊酰氯，高产率得到中间体3‑氯‑N‑羟基‑2,2‑二甲基丙酰胺，然后在环合制的4,4‑二甲基‑3‑异噁唑酮，无需分离直接在我们首创的片碱催化下苄基化制得2‑(2‑氯苯基)甲基‑4,4‑二甲基‑3‑异噁唑酮。本发明方法与现有文献方法相比，创新的使用自制的醚类催化剂使得第一步产率有显著提升，产品的含量和光学纯度高。在最后一步苄基化反应中为了提高产率使用了片碱，而且反应全程使用水作为溶剂，成本低廉，回收和后处理简单，反应温和且中间控制简单。本发明制备方法反应原料易得、反应温和、收率高、分离和纯化简单、成本低且制备过程环境友好。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

Preparation method of clomazone

Technical Field

The invention relates to a novel preparation method of a herbicide clomazone for inhibiting preemergence of pigments, and relates to the fields of oximation, cyclization, condensation and the like.

Background

Clomazone is a high-efficiency, low-toxicity and isoxazolone selective pre-emergence herbicide, is mainly used for preventing and removing broadleaf weeds and gramineous weeds in soybean fields, and can also be used for weeding in cassava, corn, rape, sugarcane and tobacco fields. The preparation methods reported in the literature at present are mainly as follows: the o-chlorobenzaldehyde method mainly uses o-chlorobenzaldehyde as the initial raw material, firstly o-chlorobenzaldehyde and salt

The method comprises the following steps of reacting hydroxylamine acid to generate oxime, reducing the oxime to obtain o-chlorobenzyl hydroxylamine, reacting the o-chlorobenzyl hydroxylamine with 3-chloro-2, 2-dimethylpropionyl chloride to obtain 3-chloro-N- (2-chlorobenzyl) -N-hydroxy-2, 2-dimethylpropionamide, and closing the ring of the 3-chloro-N- (2-chlorobenzyl) -N-hydroxy-2, 2-dimethylpropionamide under the action of alkali to obtain the 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone.

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

The other synthesis method is a chloro pivaloyl chloride method, 3-chloro-2, 2-dimethylpropionyl chloride or 3-bromo-2, 2-dimethylpropionyl chloride is used as a raw material, and the synthesis of 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone is finally completed through ammonolysis, cyclization and benzylation. The method is improved by Liuwei Dong, Tang Dexiu and other people, but the yield is not high when 3-chloro-N-hydroxy-2, 2-dimethylpropionamide is synthesized, so that the final reaction yield is improved to a small extent, the treatment steps are complicated, and the method is not suitable for industrial production.

Disclosure of Invention

The invention aims to provide a method which is simple, easy, low in cost and environment-friendly and is suitable for industrially preparing clomazone. Comprises the following steps: 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;

further, 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.

Further, 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.

Further, the benzylation reaction uses caustic soda flakes as a catalyst.

The invention has the advantages that: the invention provides a reaction system completely using water as a solvent, wherein hydroxylamine hydrochloride is used as a raw material, chloro pivaloyl chloride is dropwise added under the action of a self-made ether catalyst to obtain an intermediate 3-chloro-N-hydroxy-2, 2-dimethyl propionamide with high yield, and then 4, 4-dimethyl-3-isoxazolone prepared by cyclization is directly benzylated under the catalysis of caustic soda flakes initiated by people without separation to prepare the 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone. Compared with the existing literature methods, the method of the invention innovatively uses the self-made ether catalyst, so that the yield of the first step is obviously improved, and the content and the optical purity of the product are high. In the final step of the benzylation reaction, caustic soda flakes are used for improving the yield, water is used as a solvent in the whole reaction process, the cost is low, the recovery and the post-treatment are simple, the reaction is mild, and the intermediate control is simple. In conclusion, the preparation method has the advantages of easily available reaction raw materials, mild reaction, high yield, simple separation and purification, low cost, environment-friendly preparation process and good industrial application prospect.

Detailed Description

Example one:

step one, 18.8g (0.26mol) of hydroxylamine hydrochloride and 100ml of distilled water and 2g of self-made ether catalyst are added into a 250ml four-mouth bottle, wherein the crown ether is 18-crown-6-ether, and the molar ratio of tetrahydrofuran to 18-crown-6-ether is 1: 0.2; stirring the mixture in an ice salt bath at (-5-0 ℃) and dropwise adding a 30% NaOH solution to enable the pH value of the solution to reach 7.2. 6ml (0.2mol) of chlorotetradecanoyl chloride was then added dropwise, while a 30% NaOH solution was added dropwise, so that the pH of the system was maintained at 7.2. + -. 0.1. After the dropwise addition is finished within 1.5h, stirring for 3h at room temperature. After the reaction is finished, filtering and drying to obtain a white solid, namely the 3-chloro-N-hydroxy-2, 2-dimethylpropionamide. Content 99.0% (HPLC), yield 95.3%.

Step two:

to a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer, and a mechanical stirring device, 15.2g of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide (prepared by the first step) and 55ml of distilled water were added, and stirred vigorously at 45 ℃. 30% NaOH solution is added dropwise until the solid is completely dissolved, at which point the pH is 8.2. The dropwise addition of 30% NaOH solution was continued to pH9.0 and stirring was continued at this temperature for 3h, during which time the pH was maintained at 9.0. + -. 0.1 with additional lye. Then 0.6g of NaOH solid is added, and the reaction is carried out for 18h at the temperature of 20 ℃ to obtain 4, 4-dimethylisoxazol-3-one reaction solution. The reaction solution is not required to be separated and can be directly used for the next reaction. Content 97.2% (HPLC).

The reaction solution (containing 97.2% of 4, 4-dimethylisoxazol-3-one) after the last step of cyclization is heated to 90 ℃, 0.6g of NaOH solid and 0.4g of tetrabutylammonium bromide as a catalyst are added, 16.1g of o-chlorobenzyl chloride is added dropwise, and the dropwise addition is completed within 0.5 h. Keeping the temperature at 90 ℃ for 5 h. After the reaction is finished, cooling to room temperature, extracting for three times by using 30ml of ethyl acetate, and removing the solvent from the oil phase to obtain a light yellow oily substance, namely a clomazone crude product. The yield thereof was found to be 94% and the total yield thereof was found to be 87.1%.

Example two:

step one, 18.8g (0.26mol) of hydroxylamine hydrochloride and 100ml of distilled water and 2g of self-made ether catalyst are added into a 250ml four-mouth bottle, wherein the crown ether is 18-crown-6-ether, and the molar ratio of tetrahydrofuran to 18-crown-6-ether is 1: 0.17; stirring the mixture in an ice salt bath at (-5-0 ℃) and dropwise adding a 50% NaOH solution to enable the pH value of the solution to reach 7.2. 6ml (0.2mol) of chlorotetradecanoyl chloride was then added dropwise, while a 50% NaOH solution was added dropwise, so that the pH of the system was maintained at 7.2. + -. 0.1. After the dropwise addition is finished within 1.5h, stirring for 3h at room temperature. After the reaction is finished, filtering and drying to obtain a white solid, namely the 3-chloro-N-hydroxy-2, 2-dimethylpropionamide. Content 99.0% (HPLC), yield 93.3%.

Step two:

to a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer, and a mechanical stirring device, 15.2g of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide (prepared by the first step) and 55ml of distilled water were added, and stirred vigorously at 45 ℃. 30% NaOH solution is added dropwise until the solid is completely dissolved, at which point the pH is 8.2. The dropwise addition of 50% NaOH solution was continued to pH9.0 and stirring was continued at this temperature for 3h, during which time the pH was maintained at 9.0. + -. 0.1 with additional lye. Then 0.6g of NaOH solid is added, and the reaction is carried out for 20h at the temperature of 20 ℃ to obtain 4, 4-dimethylisoxazol-3-one reaction solution. The reaction solution is not required to be separated and can be directly used for the next reaction. Content 98.2% (HPLC).

The reaction solution (containing 97.2% of 4, 4-dimethylisoxazol-3-one) after the last step of cyclization is heated to 90 ℃, 0.6g of NaOH solid and 0.4g of tetrabutylammonium bromide as a catalyst are added, 16.1g of o-chlorobenzyl chloride is added dropwise, and the dropwise addition is finished within 1 hour. Keeping the temperature at 90 ℃ for 5 h. After the reaction is finished, cooling to room temperature, extracting for three times by using 30ml of ethyl acetate, and removing the solvent from the oil phase to obtain a light yellow oily substance, namely a clomazone crude product. The yield thereof was found to be 89%, and the total yield thereof was found to be 82.7%.

Example three:

step one, 18.8g (0.26mol) of hydroxylamine hydrochloride and 100ml of distilled water and 2g of self-made ether catalyst are added into a 250ml four-mouth bottle, wherein the crown ether is 18-crown-6-ether, and the molar ratio of tetrahydrofuran to 18-crown-6-ether is 1: 0.26; stirring the mixture in an ice salt bath at (-5-0 ℃) and dropwise adding a 30% KOH solution to enable the pH value of the solution to reach 7.2. 6ml (0.2mol) of chlorotetradecanoyl chloride was then added dropwise, while a 30% KOH solution was added dropwise, so that the pH of the system was maintained at 7.2. + -. 0.1. After the dropwise addition is finished within 1.5h, stirring for 3h at room temperature. After the reaction is finished, filtering and drying to obtain a white solid, namely the 3-chloro-N-hydroxy-2, 2-dimethylpropionamide. Content 99.0% (HPLC), yield 94.3%.

Step two:

to a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer, and a mechanical stirring device, 15.2g of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide (prepared by the first step) and 55ml of distilled water were added, and stirred vigorously at 45 ℃. 30% NaOH solution is added dropwise until the solid is completely dissolved, at which point the pH is 8.2. The addition of 30% KOH solution was continued to pH9.0 and stirring was continued at this temperature for 3h, during which time the pH was maintained at 9.0. + -. 0.1 with additional lye. Then 0.6g of NaOH solid is added, and the reaction is carried out for 18h at the temperature of 20 ℃ to obtain 4, 4-dimethylisoxazol-3-one reaction solution. The reaction solution is not required to be separated and can be directly used for the next reaction. Content 98.2% (HPLC).

The reaction solution (containing 97.2% of 4, 4-dimethylisoxazol-3-one) after the last step of cyclization is heated to 90 ℃, 0.6g of NaOH solid and 0.4g of tetrabutylammonium bromide as a catalyst are added, 16.1g of o-chlorobenzyl chloride is added dropwise, and the dropwise addition is completed within 1.5 h. Keeping the temperature at 90 ℃ for 5 h. After the reaction is finished, cooling to room temperature, extracting for three times by using 30ml of ethyl acetate, and removing the solvent from the oil phase to obtain a light yellow oily substance, namely a clomazone crude product. The yield thereof was found to be 80% and the total yield thereof was found to be 75.4%.

Example four (comparative):

step one, 18.8g (0.26mol) of hydroxylamine hydrochloride and 100ml of distilled water are added into a 250ml four-mouth bottle, stirred under an ice salt bath (-5-0 ℃) and added with 30% NaOH solution dropwise to enable the pH value of the solution to reach 7.2. 7.8ml (0.26mol) of chlorotetradecanoyl chloride was then added dropwise, while a 30% NaOH solution was added dropwise, so that the pH of the system was maintained at 7.2. + -. 0.1. After the dropwise addition is finished within 1.5h, stirring for 3h at room temperature. After the reaction is finished, filtering and drying to obtain a white solid, namely the 3-chloro-N-hydroxy-2, 2-dimethylpropionamide. Content 85.0% (HPLC), yield 76.7%.

Step two:

to a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer, and a mechanical stirring device, 15.2g of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide (prepared by the first step) and 55ml of distilled water were added, and stirred vigorously at 45 ℃. 30% NaOH solution is added dropwise until the solid is completely dissolved, at which point the pH is 8.2. The dropwise addition of 30% NaOH solution was continued to pH9.0 and stirring was continued at this temperature for 3h, during which time the pH was maintained at 9.0. + -. 0.1 with additional lye. Then 0.6g of NaOH solid is added, and the reaction is carried out for 18h at the temperature of 20 ℃ to obtain 4, 4-dimethylisoxazol-3-one reaction solution. The reaction solution was used directly in the next reaction without separation, with a content of 88.6% (HPLC).

The reaction solution (containing 97.2% of 4, 4-dimethylisoxazol-3-one) after the last step of cyclization is heated to 100 ℃, 0.6g of NaOH solid and 0.4g of tetrabutylammonium bromide as a catalyst are added, 16.1g of o-chlorobenzyl chloride is added dropwise, and the dropwise addition is completed within 0.5 h. Keeping the temperature at 90 ℃ for 5 h. After the reaction is finished, cooling to room temperature, extracting for three times by using 30ml of ethyl acetate, removing the solvent from the oil phase to obtain a light yellow oily substance, namely a clomazone crude product, wherein the yield is 81.2 percent, and the total yield is 69.5 percent.

Claims

1. a 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 used 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;

.

2. the preparation method of a kind of clomazone according to claim 1, is characterized in that, described cyclic ether is tetrahydrofuran, described crown ether is 18-crown-6-ether, described tetrahydrofuran and 18- The molar ratio of crown-6-ether is 1:0.1-0.3.

3. the preparation method of a kind of clomazone according to claim 2, is characterized in that, the preparation method of described ether catalyst, wherein the tetrahydrofuran of 1/3-2/3 is input in the reactor earlier, The 18-crown-6-ether was then added, and the remaining tetrahydrofuran was then added to the reactor with stirring as it was added.

4. the preparation method of a kind of clomazone according to claim 1, is characterized in that, benzylation reaction uses flake base as catalyzer.