阅读说明：本技术 一种1-[2-(2,4-二氯苯基)-2羟基乙基]-1h咪唑的合成方法 (Synthetic method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole ) 是由 赵振东 潘光飞 郭俊 雷鹏飞 周智超 王进 曾挺 于 2021-08-12 设计创作，主要内容包括：本发明公开了一种1-[2-(2,4-二氯苯基)-2羟基乙基]-1H咪唑的合成方法,以2,2,4-三氯苯乙酮为原料,DMF为溶剂,碱性条件下分子内成环,再与咪唑钠盐反应,反应直接制得1-[2-(2,4-二氯苯基)-2羟基乙基]-1H咪唑,产品脱溶后含量达95％以上,以2,2,4-三氯苯乙酮计收率达93％以上,操作方便,收率高,为合成抑霉唑关键中间体1-[2-(2,4-二氯苯基)-2羟基乙基]-1H咪唑提供了一条新途径。(The invention discloses a synthesis method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole, which takes 2,2, 4-trichloroacetophenone as a raw material, DMF as a solvent, intramolecular cyclization is carried out under an alkaline condition, then the product reacts with imidazole sodium salt to directly prepare 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole, the content of the product after desolventization reaches more than 95 percent, the yield based on 2,2, 4-trichloroacetophenone reaches more than 93 percent, the operation is convenient, the yield is high, and a new way is provided for synthesizing imazalil key intermediate 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole.)

1. A synthetic method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole is characterized by comprising the following steps:

adding 200-500 mL of DMF, 120-135 g of 98% 2,2, 4-trichloroacetophenone into a bottle, stirring until the materials are dissolved, adding 18-45 g of flaky sodium hydroxide, heating to 55-80 ℃ under negative pressure, keeping the temperature while slowly removing the DMF, removing 100-350 mL of DMF after 3-6H, sampling for analysis, adding 55-72 g of imidazole sodium salt in batches at the temperature after the reaction is finished, keeping the temperature for 2-5H after the addition is finished, then removing the DMF under reduced pressure, adding 90-120 g of toluene and 90-120 g of water, cooling to 10-25 ℃, filtering and drying to obtain the 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole.

2. The method of synthesizing 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole according to claim 1, comprising the steps of:

adding 300mL of DMF, 125g of 98% 2,2, 4-trichloroacetophenone into a bottle, stirring until the materials are dissolved, adding 22g of flake sodium hydroxide, heating to 70 ℃ under negative pressure, keeping the temperature while slowly removing the DMF, removing 100mL of DMF after 5H, sampling, analyzing, finishing the reaction, adding 59g of imidazole sodium salt in batches at the temperature, keeping the temperature for 3H after the addition is finished, then decompressing to remove the DMF, adding 100g of toluene and 100g of water, cooling to 15 ℃, filtering, and drying to obtain the 1- [2- (2, 4-dichlorophenyl) -2-hydroxyethyl ] -1H-imidazole.

3. The method of synthesizing 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole according to claim 1, comprising the steps of:

adding 400mL of DMF, 125g of 98% 2,2, 4-trichloroacetophenone into a bottle, stirring until the materials are dissolved, adding 36g of flaky sodium hydroxide, heating to 60 ℃ under negative pressure, keeping the temperature while slowly removing the DMF, removing 200mL of DMF after 4H, sampling, analyzing, finishing the reaction, adding 64g of imidazole sodium salt in batches at the temperature, keeping the temperature for 2H after the addition is finished, then decompressing to remove the DMF, adding 100g of toluene and 100g of water, cooling to 15 ℃, filtering, and drying to obtain the 1- [2- (2, 4-dichlorophenyl) -2-hydroxyethyl ] -1H-imidazole.

4. The method for synthesizing 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole according to any one of claims 1 to 3, wherein the content of the 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole is not less than 95%.

Technical Field

The invention relates to the technical field of organic chemical synthesis, in particular to a synthesis method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole.

Background

Imazalil is a systemic fungicide with broad antimicrobial spectrum and has protection and treatment effects, not only has control effects on a plurality of fungal diseases of fruits, vegetables and ornamental plants, but also can be used for storing and rotting after the harvest of citrus, bananas and other fruits, has high activity on Helminthosporium, Fusarium, Septoria and the like, and can be used for controlling cereal diseases and treating seeds. 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole is a key intermediate for chemical synthesis of imazalil, and the molecular structure of the intermediate is as follows:

the existing method for synthesizing 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole is to prepare alpha chloromethyl-2, 4-dichlorobenzyl alcohol by using 2,2, 4-trichloroacetophenone as a raw material through reduction and hydrolysis in alcohol, then react the alpha chloromethyl-2, 4-dichlorobenzyl alcohol with imidazole sodium salt in DMF to prepare an intermediate 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole, wherein the content of the intermediate is over 95 percent after refining, and the yield is only 80 percent based on the 2,2, 4-trichloroacetophenone. The traditional method for synthesizing 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole has the disadvantages of complicated reaction steps, low yield and high cost.

The reaction equation for synthesizing 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole is as follows:

disclosure of Invention

In view of this, the present invention provides a method for synthesizing 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole, so as to solve the above technical problems.

The invention provides the following technical scheme:

a synthetic method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole comprises the following steps:

adding 200-500 mL of DMF, 120-135 g of 98% 2,2, 4-trichloroacetophenone into a bottle, stirring until the materials are dissolved, adding 18-45 g of flaky sodium hydroxide, heating to 55-80 ℃ under negative pressure, keeping the temperature while slowly removing the DMF, removing 100-350 mL of DMF after 3-6H, sampling for analysis, adding 55-72 g of imidazole sodium salt in batches at the temperature after the reaction is finished, keeping the temperature for 2-5H after the addition is finished, then removing the DMF under reduced pressure, adding 90-120 g of toluene and 90-120 g of water, cooling to 10-25 ℃, filtering and drying to obtain the 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole.

Preferably, the synthesis method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole comprises the following steps:

adding 300mL of DMF, 125g of 98% 2,2, 4-trichloroacetophenone into a bottle, stirring until the materials are dissolved, adding 22g of flake sodium hydroxide, heating to 70 ℃ under negative pressure, keeping the temperature while slowly removing the DMF, removing the DMF100mL after 5H, sampling and analyzing, after the reaction is finished, adding 59g of imidazole sodium salt in batches at the temperature, keeping the temperature for 3H after the addition is finished, then decompressing to remove the DMF, adding 100g of toluene and 100g of water, cooling to 15 ℃, filtering, and drying to obtain the 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole.

Preferably, the synthesis method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole comprises the following steps:

adding 400mL of DMF, 125g of 98% 2,2, 4-trichloroacetophenone into a bottle, stirring until the materials are dissolved, adding 36g of flaky sodium hydroxide, heating to 60 ℃ under negative pressure, keeping the temperature while slowly removing the DMF, removing the DMF200mL after 4H, sampling, analyzing, finishing the reaction, adding 64g of imidazole sodium salt in batches at the temperature, keeping the temperature for 2H after the addition is finished, then decompressing to remove the DMF, adding 100g of toluene and 100g of water, cooling to 15 ℃, filtering, and drying to obtain the 1- [2- (2, 4-dichlorophenyl) -2-hydroxyethyl ] -1H-imidazole.

Preferably, the content of the prepared 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole is more than or equal to 95 percent.

According to the technical scheme, the invention has the beneficial effects that:

the invention relates to a synthesis method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole, which takes 2,2, 4-trichloroacetophenone as a raw material and DMF as a solvent, performs intramolecular cyclization under an alkaline condition, then reacts with imidazole sodium salt to prepare the 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole by a one-pot method, the content of the product after desolventization reaches more than 95 percent, and the yield based on the 2,2, 4-trichloroacetophenone reaches more than 93 percent, so the method has the advantages of convenient operation and high yield, and provides a new way for synthesizing the imazalil key intermediate 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. The exemplary embodiments and descriptions of the present invention are provided to explain the present invention, but not to limit the present invention.

Example 1

Synthetic method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole

Adding 200mL of DMF, 120g of 98% 2,2, 4-trichloroacetophenone into a bottle, stirring until the mixture is dissolved, adding 18g of flaky sodium hydroxide, heating to 55 ℃ under negative pressure, keeping the temperature while slowly removing the DMF, removing the DMF150mL after 3H, sampling and analyzing, after the reaction is finished, adding 55g of imidazole sodium salt in batches at the temperature, keeping the temperature for 2H after the addition is finished, then removing the DMF under reduced pressure, adding 90g of toluene and 90g of water, cooling to 10 ℃, filtering and drying to obtain 137.6g of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole, wherein the content is 94.9%, and the reaction yield is 93.2%.

Example 2

A synthesis method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole comprises the steps of adding 300mL of DMF, 125g of 98% 2,2, 4-trichloroacetophenone into a bottle, stirring until the mixture is dissolved, adding 22g of flake sodium hydroxide, heating to 70 ℃ under negative pressure, keeping the temperature while slowly removing the DMF, removing 100mL of DMF after 5H, sampling for analysis, adding 59g of imidazole sodium salt in batches after the reaction is finished, keeping the temperature for 3H after the addition is finished, then removing the DMF under reduced pressure, adding 100g of toluene and 100g of water, cooling to 15 ℃, filtering and drying to obtain 138.5g of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole, wherein the content is 95.2%, and the reaction yield is 93.6%.

Example 3

A synthesis method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole comprises the steps of adding 400mL of DMF and 125g of 98% 2,2, 4-trichloroacetophenone into a bottle, stirring until the mixture is dissolved, adding 36g of flake sodium hydroxide, heating to 60 ℃ under negative pressure, keeping the temperature while slowly removing the DMF, removing 200mL of DMF after 4H, sampling for analysis, adding 64g of imidazole sodium salt in batches after the reaction is finished, keeping the temperature for 2H after the addition is finished, then removing the DMF under reduced pressure, adding 100g of toluene and 100g of water, cooling to 15 ℃, filtering and drying to obtain 137.5g of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole, wherein the content is 95.5%, and the reaction yield is 93.2%.

Example 4

Synthetic method of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole

Adding 135g of 98% DMF (dimethyl formamide) 2,2, 4-trichloroacetophenone into a bottle, stirring until the materials are dissolved, adding 45g of flaky sodium hydroxide, heating to 80 ℃ under negative pressure, slowly removing the DMF while keeping the temperature, removing 350mL of the DMF after 6H, sampling and analyzing, after the reaction is finished, adding 72g of imidazole sodium salt in batches at the temperature, keeping the temperature for 5H after the addition is finished, then removing the DMF under reduced pressure, adding 120g of toluene and 120g of water, cooling to 25 ℃, filtering and drying to obtain 140.1g of 1- [2- (2, 4-dichlorophenyl) -2 hydroxyethyl ] -1H imidazole with the content of 96.2% and the reaction yield of 95.6%.

The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes may be made to the embodiment of the present invention by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.