CN111170908B

CN111170908B - A kind of synthetic method of 2,4-dimethyl-3-methanesulfonyl halide benzene

Info

Publication number: CN111170908B
Application number: CN202010024011.9A
Authority: CN
Inventors: 刘博文; 赵优; 张依晗; 黄淑益; 李福芸
Original assignee: Beijing Institute of Graphic Communication
Current assignee: Beijing Institute of Graphic Communication
Priority date: 2020-01-09
Filing date: 2020-01-09
Publication date: 2021-08-17
Anticipated expiration: 2040-01-09
Also published as: CN111170908A

Abstract

The invention discloses a method for synthesizing 2, 4-dimethyl-3-methylsulfonyl halogenobenzene, which comprises the steps of firstly carrying out sulfhydrylation on 2, 6-dimethylaniline serving as a raw material in a system with tert-butyl nitrite and copper powder serving as catalysts by using dimethyldisulfide, finally carrying out oxidation by using peracetic acid, extracting reaction liquid by using dichloromethane after the reaction is finished, drying and spin-drying to obtain 2, 6-dimethylmethylsulfonyl benzene, adding a halogenating reagent into the obtained 2, 6-dimethylmethylsulfonyl benzene in a concentrated sulfuric acid system for reaction, adding water after the reaction is finished, filtering and drying to obtain the 2, 4-dimethyl-3-methylsulfonyl halogenobenzene. The raw materials are easy to obtain, the route is feasible, the operation is simple, the product purity is high, and the cost is low.

Description

Synthesis method of 2, 4-dimethyl-3-methylsulfonyl halogeno-benzene

Technical Field

The invention relates to the technical field of pharmaceutical chemicals, in particular to a synthetic method of 2, 4-dimethyl-3-methylsulfonyl halogenobenzene.

Background

The 2, 4-dimethyl-3-methylsulfonyl iodobenzene is a white powdery solid and is an important pesticide intermediate raw material, and the existing synthetic method of the 2, 4-dimethyl-3-methylsulfonyl halobenzene generally has the defects of complex operation process, low product purity, high cost and the like.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide a method for synthesizing 2, 4-dimethyl-3-methylsulfonyl halogenobenzene.

In order to achieve the purpose, the invention adopts the following technical scheme:

a method for synthesizing 2, 4-dimethyl-3-methylsulfonyl halogenobenzene comprises the following steps:

s1, preparing 2, 6-dimethyl methyl mercapto benzene by using 2, 6-dimethyl aniline as a raw material:

2, 6-dimethylaniline is taken out and put into a reaction vessel, dimethyldisulfide and copper powder are added under stirring and heated; then, dropwise adding tert-butyl nitrite; monitoring by TLC, cooling the reaction solution, adding 40mL of dichloromethane, filtering, washing the filtrate with acid, dissolving flocculent copper salt in water, separating liquid to obtain an organic phase, washing the organic phase with water, drying the organic phase, and spin-drying to obtain solid 2, 6-dimethylmethylmercaptobenzene;

s2, oxidation:

taking solid 2, 6-dimethyl methylmercaptobenzene into a reaction bottle, adding dichloromethane, stirring and dissolving, dripping peroxyacetic acid aqueous solution at normal temperature, and monitoring by TLC (thin layer chromatography) until the raw materials disappear; adding dichloromethane and deionized water, separating in a separating funnel, extracting the water phase twice with dichloromethane, combining the organic phase, drying, and spin-drying to obtain solid 2, 6-dimethyl methylsulfonyl benzene;

s3, halo:

taking 2, 6-dimethylmethylsulfonylbenzene in a new reaction bottle, adding concentrated sulfuric acid, carrying out ice bath, adding a halogenating reagent for multiple times, stirring for 2 hours in ice bath, and then stirring at room temperature overnight; and monitoring by TLC, after the reaction is finished, adding deionized water into the reaction bottle, separating out a solid, and filtering to obtain a final product, namely 2, 4-dimethyl-3-methylsulfonyl iodobenzene.

Further, in step S1, the molar ratio of 2, 6-dimethylaniline to tert-butyl nitrite is 1: 2.25.

further, in step S1, the molar ratio of 2, 6-dimethylaniline to copper powder is 1: 0.75.

further, in step S1, the reaction temperature is 50 ℃ to 60 ℃, preferably 55 ℃.

Further, in step S2, the molar ratio of 2, 6-dimethylmethylmercaptobenzene to peroxyacetic acid is 1: 1.86.

further, in step S3, the molar ratio of the 2, 6-dimethylmethanesulfonylbenzene to the halogenating agent is 1: 1-1.3.

Further, in step S3, the temperature of the ice bath is-5 ℃ to 5 ℃.

The invention has the beneficial effects that: according to the method, 2, 6-dimethylaniline is used as a raw material, firstly, dimethyldisulfide is subjected to sulfhydrylation in a system with tert-butyl nitrite and copper powder as catalysts, finally, peroxyacetic acid is used for oxidation, after the reaction is finished, dichloromethane is used for extracting reaction liquid, drying and spin-drying are carried out to obtain 2, 6-dimethylmethylsulfonylbenzene, the obtained 2, 6-dimethylmethylsulfonylbenzene is added with a halogenating reagent in a concentrated sulfuric acid system for reaction, and after the reaction is finished, water is added, and filtration and drying are carried out to obtain the 2, 4-dimethyl-3-methylsulfonylbenzene halide. The raw materials are easy to obtain, the route is feasible, the operation is simple, the product purity is high, and the cost is low.

Detailed Description

The present invention will be further described below, and it should be noted that the present embodiment is based on the technical solution, and a detailed implementation manner and a specific operation process are provided, but the protection scope of the present invention is not limited to the present embodiment.

2, 6-dimethylaniline is taken out and put into a reaction vessel, dimethyldisulfide and copper powder are added under stirring and heated; then, dropwise adding tert-butyl nitrite; and monitoring by TLC (thin layer chromatography), cooling the reaction solution, adding dichloromethane, filtering, washing the filtrate with acid, dissolving flocculent copper salt in water, separating the solution to obtain an organic phase, washing the organic phase with water, drying the organic phase, and performing spin drying to obtain solid 2, 6-dimethylmethylmercaptobenzene.

The reaction equation is:

further, the molar ratio of the 2, 6-dimethylaniline to the tert-butyl nitrite is 1: 2.25;

further, the molar ratio of the 2, 6-dimethylaniline to the copper powder is 1: 0.75;

further, the molar ratio of 2, 6-dimethylaniline to dimethyldisulfide was 1: 9.04.

Further, the reaction temperature is 50 ℃ to 60 ℃, preferably 55 ℃.

Specifically, in this example, 1.21 g (10mmol) of 2, 6-dimethylaniline was taken in a three-necked flask, and 8mL (90.4mmol) of dimethyldisulfide and copper powder 480 were added under stirring and heated to 55 ℃; 1.545 g (15mmol) of tert-butyl nitrite is added dropwise, and the raw material is monitored to be remained in the reaction process, so 0.75 g (7.28mmol) of tert-butyl nitrite is added, and 2.259 g (22.5mmol) of tert-butyl nitrite is shared in the total process; and monitoring by TLC, cooling the reaction liquid, adding 40mL of dichloromethane, filtering, washing the filtrate with acid, dissolving flocculent copper salt in water, separating liquid to obtain an organic phase, washing the organic phase with water, drying the organic phase, and performing spin drying to obtain solid 2, 6-dimethylmethylmercaptobenzene with the yield of 57.3%.

S2, oxidation:

taking solid 2, 6-dimethyl methylmercaptobenzene into a reaction bottle, adding dichloromethane, stirring and dissolving, dripping peroxyacetic acid aqueous solution at normal temperature, and monitoring by TLC (thin layer chromatography) until the raw materials disappear; adding dichloromethane and deionized water, separating in a separating funnel, extracting the water phase twice with dichloromethane, combining the organic phase, drying and spin-drying to obtain solid 2, 6-dimethyl methylsulfonyl benzene.

The reaction equation is:

further, the molar ratio of the 2, 6-dimethyl methylmercaptobenzene to the peroxyacetic acid is 1: 1.86 of the total weight of the product;

further, the preparation process of the peroxyacetic acid comprises the following steps: adding 125 g of 30% hydrogen peroxide into 1-2 ml of concentrated sulfuric acid, stirring at normal temperature, dropwise adding 75 g of glacial acetic acid, and stirring for 12 hours.

In this example, specifically, 3.6836 g (20mmol) of solid 2, 6-dimethylmethylmercaptobenzene was put into a single-neck flask, 10mL of dichloromethane was added and stirred to dissolve, 2mol/L aqueous peroxyacetic acid solution was added dropwise at normal temperature, and TLC monitoring was carried out until the starting material disappeared, and the amount of the aqueous peroxyacetic acid solution was 18.6 mL; adding 20mL of dichloromethane and 10mL of deionized water, separating in a separating funnel, extracting the aqueous phase twice by using 10mL of dichloromethane, combining the organic phase, drying and spin-drying to obtain solid 2, 6-dimethyl methylsulfonylbenzene. The yield thereof was found to be 86.5%.

S3, halo:

Further, the molar ratio of the 2, 6-dimethylmethanesulfonylbenzene to the halogenating agent is 1: 1-1.3, preferably 1: 1.2, 1:1.1 and 1: 1;

further, the temperature of the ice bath is-5 ℃ to 5 ℃.

Specifically, in this example, 1.84 g (10mmol) of 2, 6-dimethylmethylsulfonylbenzene was put into a single-neck bottle, 20mL of concentrated sulfuric acid was added, the mixture was cooled to 5 ℃ or below in ice, 2.25 g (10mmol) of NIS was added in small amounts, the mixture was stirred for 2 hours in ice bath, and then the mixture was stirred at room temperature overnight; and monitoring by TLC, after the reaction is finished, adding 20mL of deionized water into a reaction bottle, separating out a solid, and filtering to obtain a final product, namely 2, 4-dimethyl-3-methylsulfonyl iodobenzene. The yield was 81.6%.

Further, the molar ratio of the 2, 6-dimethylmethanesulfonylbenzene to the NIS may be further selected to be 1: 1-1.3, more preferably 1: 1.2, 1:1.1 and 1:1.

Various corresponding changes and modifications can be made by those skilled in the art based on the above technical solutions and concepts, and all such changes and modifications should be included in the protection scope of the present invention.

Claims

1. a synthetic method of 2,4-dimethyl-3-methanesulfonyl halide benzene, is characterized in that, comprises the steps:

S1. Using 2,6-dimethylaniline as raw material to generate 2,6-dimethylmercaptobenzene:

Take 2,6-dimethylaniline in the reaction vessel, add dimethyl disulfide and copper powder under stirring and heat; then add tert-butyl nitrite dropwise; TLC monitoring, the reaction is over, cool the reaction solution, add 40ml Dichloromethane, filtered, the filtrate was acid washed, the flocculent copper salt was dissolved in water, the organic phase was separated by liquid separation, the organic phase was washed with water, the organic phase was dried, and spin-dried to obtain solid 2,6-dimethylmercaptobenzene ;

S2, oxidation:

Take solid 2,6-dimethylmercaptobenzene in a reaction flask, add dichloromethane and stir to dissolve, dropwise add peracetic acid aqueous solution at room temperature, and monitor by TLC until the raw materials disappear; add dichloromethane and deionized water, Separation is carried out in a separating funnel, the aqueous phase is extracted twice with dichloromethane, the organic phases are combined, dried, and spin-dried to obtain solid 2,6-dimethylmethanesulfonylbenzene;

S3, halogenated:

Take 2,6-dimethylmethanesulfonylbenzene into a new reaction flask, add concentrated sulfuric acid, ice bath, add halogenated reagents in several times, stir in ice bath for 2 h, and then stir at room temperature overnight; TLC monitoring shows that after the reaction is over, Take deionized water and add it to the reaction flask, the solid is precipitated, and the final product, 2,4-dimethyl-3-methanesulfonyl iodobenzene, is obtained by filtration.

2. The synthetic method according to claim 1, wherein in step S1, the molar ratio of the 2,6-dimethylaniline to tert-butyl nitrite is 1:2.25.

3. The synthetic method according to claim 1, wherein in step S1, the molar ratio of the 2,6-dimethylaniline to the copper powder is 1:0.75.

4. The synthetic method according to claim 1, wherein in step S1, the reaction temperature is 50°C-60°C.

5. The synthetic method according to claim 4, wherein in step S1, the reaction temperature is 55°C.

6. The synthetic method according to claim 1, wherein in step S2, the molar ratio of the 2,6-dimethylmercaptobenzene to peracetic acid is 1:1.86.

7 . The synthesis method according to claim 1 , wherein, in step S3, the molar ratio of the 2,6-dimethylmethanesulfonylbenzene to the halogenating reagent is 1:1-1.3. 8 .

8. The synthesis method according to claim 1, wherein in step S3, the temperature of the ice bath is -5°C to 5°C.