阅读说明：本技术 2-(2-氯苯基)甲基-4,4-二甲基-3-异恶唑酮的制备方法 (Preparation method of 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone ) 是由 魏凤 张晓谦 米鹏 陈琦 冯维春 田达 鲁琳琳 邢文国 舒永 姚斌 于 2021-08-31 设计创作，主要内容包括：本发明属于有机合成技术领域,具体涉及一种2-(2-氯苯基)甲基-4,4-二甲基-3-异恶唑酮的制备方法。本发明以4,4-二甲基-3-异噁唑酮、邻氯氯苄为原料,在缚酸剂存在下,控制反应体系pH维持在8.5～9.5反应,反应完毕,经后处理,最终制得2-(2-氯苯基)甲基-4,4-二甲基-3-异恶唑酮。本发明转化率及收率高、副产少,产品后处理简单,符合绿色循环经济理念,解决了原有邻氯苯甲醛肟化法转化率不高、氯代特戊酰氯肟化反应杂质多、产品质量不高等技术难题。(The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone. According to the method, 4-dimethyl-3-isoxazolone and o-chlorobenzyl chloride are used as raw materials, the pH value of a reaction system is controlled to be maintained at 8.5-9.5 in the presence of an acid binding agent for reaction, and after the reaction is finished, the 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone is finally prepared through post-treatment. The method has the advantages of high conversion rate and yield, less by-products, simple product post-treatment, conformity with the concept of green circular economy, and solves the technical problems of low conversion rate, more impurities in the oximation reaction of chloro pivaloyl chloride, low product quality and the like of the original oximation method of o-chlorobenzaldehyde.)

The preparation method of 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone is characterized by comprising the steps of taking 4, 4-dimethyl-3-isoxazolone and o-chlorobenzyl chloride as raw materials, controlling the pH of a reaction system to be maintained at 8.5-9.5 in the presence of an acid binding agent, reacting, cooling, standing for layering, extracting and distilling to finally prepare the 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone.

2. The process for the preparation of 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone according to claim 1, wherein butyl ether is used as extractant in the extraction.

3. The process for the preparation of 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone according to claim 1, wherein the acid scavenger is diisopropylethylamine or 3-aminopyridine or a mixture thereof; 4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: acid-binding agent 1: 1.3-1.5.

4. The method for preparing 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone according to claim 1, wherein the reaction temperature is 105 to 120 ℃.

5. The method for preparing 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone according to claim 1, wherein the reaction time is 9 to 12 hours.

6. The process for the preparation of 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone according to claim 1, wherein the molar ratio of 4, 4-dimethyl-3-isoxazolone: 1: 1.2-1.3 of o-chlorobenzyl chloride.

7. The process for the preparation of 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone according to claim 1, wherein the o-chlorobenzyl chloride is added dropwise.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone.

Technical Field

The (2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone) (commonly known as clomazone) is a high-efficiency, low-toxicity and isoxazolone selective pre-emergence herbicide, which is a novel high-efficiency pesticide introduced from abroad in China. The synthesis route mainly comprises an o-chlorobenzaldehyde oximation method and a chloro pivaloyl chloride method, the most of the recent literature reports are the chloro pivaloyl chloride method, in 2006, CN110172042A discloses a low-temperature synthesis process, isomers are converted into products through chemical treatment, the purity of the products obtained by refining petroleum ether is more than 97%, and the yield reaches more than 92%; in 2014, patent CN104277008A discloses a preparation method of 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolidone, which comprises the steps of preparing 4, 4-dimethyl-3-isoxazolidone from chloro pivaloyl chloride by using water as a solvent, and reacting with 2-chlorobenzyl chloride to prepare 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolidone, wherein the yield is about 85%, and the product purity is 96%; in 2016, patent CN106749072A discloses that 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone is prepared under the action of a self-made ether catalyst, the total yield of the product is 75-85%, and the purity of the product is more than or equal to 97%; in 2018, CN108774186A discloses a bipolar membrane electrodialysis method for preparing 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone, which is low in synthesis cost and clean in production. The o-chlorobenzaldehyde oximation method has low reaction conversion rate, uses a large amount of solvent, has complicated product purification process, is not suitable for industrial production, and the chloro pivaloyl chloride oximation method has more impurities in the ring closing side reaction and is difficult to refine, thereby influencing the quality of the final 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone product, and the market purity is about 96 percent. With the increase of the using amount of the low-toxicity herbicide in the market, the preparation of the technical material with high quality and low cost is a problem to be solved urgently. The innovative synthesis process is actively explored and is imminent.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide a preparation method of a herbicide 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone.

The preparation method of the 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone takes 4, 4-dimethyl-3-isoxazolidone and o-chlorobenzyl chloride as raw materials, controls the pH of a reaction system to be maintained at 8.5-9.5 for reaction in the presence of an acid binding agent, and finally prepares the 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone through cooling, standing for layering, extraction and distillation after the reaction is finished.

Butyl ether is used as an extractant during extraction.

The acid-binding agent is diisopropylethylamine or 3-aminopyridine or a mixture thereof; 4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: acid-binding agent 1: 1.3-1.5.

The reaction temperature is 105-120 ℃, and preferably 100-110 ℃;

the reaction time is 9-12 h, preferably 10-11 h

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: 1: 1.2-1.3 of o-chlorobenzyl chloride.

The o-chlorobenzyl chloride is added dropwise.

The method has the advantages of high conversion rate, high yield and few byproducts, solves the technical problems of low reaction conversion rate, more reaction impurities in the chloracetyl pivalate oximation method, low quality of 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone products and the like in the conventional o-chlorobenzaldehyde oximation method, and the technical process conforms to the concept of green economic cycle.

The specific implementation mode is as follows:

in order to better understand the technical scheme of the present invention, the following detailed description of the present invention is provided by way of examples, but the present invention should not be construed as limited to the above description.

Example 1

A preparation method of herbicide 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone comprises the following specific steps:

(1) adding 1.0mol of water and 4, 4-dimethyl-3-isoxazolone into a reactor, heating to 110 ℃, adding o-chlorobenzyl chloride and acid-binding agent diisopropylethylamine in batches, keeping the pH value at 9.0, carrying out copolymerization reaction in the reaction kettle, and carrying out heat preservation reaction for 9 hours to obtain 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone reaction liquid;

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: o-chlorobenzyl chloride ═ 1:1.2

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: acid-binding agent 1: 1.4.

(2) and continuously keeping the pH of the reaction liquid at 9.0, cooling, standing for layering, extracting a water layer by butyl ether, combining oil layers, distilling under reduced pressure to obtain 232.5g of the product 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone, wherein the content is about 99.2 percent by liquid chromatography detection, and the total yield is about 97 percent.

Example 2

A preparation method of herbicide 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone comprises the following specific steps:

(1) adding 1.0mol of water and 4, 4-dimethyl-3-isoxazolone into a reactor, heating to 120 ℃, adding o-chlorobenzyl chloride and acid-binding agent diisopropylethylamine in batches, keeping the pH at 8.5, carrying out copolymerization reaction in the reaction kettle, and carrying out heat preservation reaction for 9 hours to obtain 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone reaction liquid;

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: o-chlorobenzyl chloride ═ 1:1.2

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: acid-binding agent 1: 1.3.

(2) and continuously keeping the pH of the reaction liquid at 8.5, cooling, standing for layering, extracting a water layer by butyl ether, combining oil layers, distilling under reduced pressure to obtain 230.6g of the product 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone, wherein the content of the 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone is about 99.2 percent by liquid chromatography detection, and the total yield is about 96.2 percent.

Example 3

A preparation method of herbicide 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone comprises the following specific steps:

(1) adding 1.0mol of water and 4, 4-dimethyl-3-isoxazolone into a reactor, heating to 120 ℃, adding o-chlorobenzyl chloride and 3-aminopyridine as acid-binding agents in batches, keeping the pH at 9.0, carrying out copolymerization reaction in a reaction kettle, and carrying out heat preservation reaction for 9 hours to obtain 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone reaction liquid;

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: o-chloro ═ 1: 1.3

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: acid-binding agent 1: 1.4.

(2) and continuously keeping the pH of the reaction liquid at 9.0, cooling, standing for layering, extracting a water layer by butyl ether, combining oil layers, distilling under reduced pressure to obtain 236.1g of the product 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone, wherein the content of the 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone is about 99.2 percent by liquid chromatography detection, and the total yield is about 98.5 percent.

Example 4

A preparation method of herbicide 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone comprises the following specific steps:

(1) adding 1.0mol of water and 4, 4-dimethyl-3-isoxazolone into a reactor, heating to 105 ℃, adding o-chlorobenzyl chloride and 3-aminopyridine as acid-binding agents in batches, keeping the pH at 9.5, carrying out copolymerization reaction in a reaction kettle, and carrying out heat preservation reaction for 12 hours to obtain 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone reaction liquid;

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: o-chloro ═ 1: 1.3

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: acid-binding agent 1: 1.5.

(2) and continuously keeping the pH of the reaction liquid at 9.5, cooling, standing for layering, extracting a water layer by butyl ether, combining oil layers, distilling under reduced pressure to obtain 234.9g of the product 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone, wherein the content of the product is about 99.2 percent by liquid chromatography detection, and the total yield is about 98 percent.

Example 5

A preparation method of herbicide 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone comprises the following specific steps:

(1) adding 1.0mol of water and 4, 4-dimethyl-3-isoxazolone into a reactor, heating to 110 ℃, adding o-chlorobenzyl chloride and 3-aminopyridine as acid-binding agents in batches, keeping the pH at 9.0, carrying out copolymerization reaction in a reaction kettle, and carrying out heat preservation reaction for 11 hours to obtain 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone reaction liquid;

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: o-chloro ═ 1: 1.3

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: acid-binding agent 1: 1.4.

(2) and continuously keeping the pH of the reaction liquid at 9.0, cooling, standing for layering, extracting a water layer by butyl ether, combining oil layers, distilling under reduced pressure to obtain 233.7g of the product 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone, wherein the content of the product is about 99.2 percent by liquid chromatography detection, and the total yield is about 97.5 percent.

Example 6

A preparation method of herbicide 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolone comprises the following specific steps:

(1) adding 1.0mol of water and 4, 4-dimethyl-3-isoxazolone into a reactor, heating to 120 ℃, adding o-chlorobenzyl chloride and acid-binding agent diisopropylethylamine in batches, keeping the pH at 8.5, carrying out copolymerization reaction in the reaction kettle, and carrying out heat preservation reaction for 10 hours to obtain 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone reaction liquid;

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: o-chloro ═ 1: 1.3

4, 4-dimethyl-3-isoxazolone, in terms of mole ratios: acid-binding agent 1: 1.3.

(2) and continuously keeping the pH of the reaction liquid at 8.5, cooling, standing for layering, extracting a water layer by butyl ether, combining oil layers, distilling under reduced pressure to obtain 231.8g of the product 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone, wherein the content of the product is about 99.2 percent by liquid chromatography detection, and the total yield is about 96.7.