CN107459471B

CN107459471B - Synthesis method of N-tert-butyl benzene sulfonamide

Info

Publication number: CN107459471B
Application number: CN201710783753.8A
Authority: CN
Inventors: 王凯; 陈强; 岳邦毅; 郝卫强
Original assignee: Changzhou High-Tech Research Institute Of Nanjing University
Current assignee: Changzhou High-Tech Research Institute Of Nanjing University
Priority date: 2017-09-04
Filing date: 2017-09-04
Publication date: 2020-06-30
Anticipated expiration: 2037-09-04
Also published as: CN107459471A

Abstract

The invention claims a method for synthesizing N-tert-butyl benzene sulfonamide, which comprises the steps of placing benzene sulfonamide, materials, a catalyst and a solvent in a four-mouth bottle, stirring, heating for reflux reaction, obtaining a reaction end point when the benzene sulfonamide as a raw material disappears, cooling the reaction product to room temperature, filtering out insoluble substances, and performing decompression and desolventization to obtain the N-tert-butyl benzene sulfonamide.

Description

Synthesis method of N-tert-butyl benzene sulfonamide

Technical Field

The invention belongs to the field of chemical synthesis, and particularly relates to a synthesis method of N-tert-butyl benzene sulfonamide.

Background

The sulfonamide compound is a substance with biological activity, and has wide application in medicine research and development and pesticide research, for example, bactericides, herbicides, insecticides, anticancer drugs and diabetes in the market all contain sulfonamide groups, wherein N-tert-butyl esterification reaction of the benzenesulfonamide is difficult to carry out due to steric effect of tert-butyl and electronic effect of the sulfonamide group, and the yield is low. The defects and shortcomings of the prior art are as follows: chen Jianyan et al reported a method for preparing N-hydrocarbyl substituted amide by catalyzing ether compounds to react with sulfonamide by using titanium tetrachloride in a document (TiCl 4-medial Direct N-Alkylation of sulfonic acids with reactive Ethers ", Synlett,2012,23,595-600), but did not report a tertiary butylation reaction with relatively poor reaction activity and larger steric hindrance effect, and the method had the problem of low yield and is not suitable for industrial production. Zhou Xinrui et al, Chinese patent CN102241614, discloses a synthesis process of an N-alkyl substituted amide compound, which adopts an ether compound as a raw material to react with an amide compound under the catalysis of a phosphotungstic heteropoly acid to prepare a target product. However, the reaction yield is generally low, and the large-scale industrial production is difficult to realize. Populus sieboldii reports in Chinese patent CN103819369 that a ternary catalytic system of ethyl triphenyl phosphonium bromide-silver compound-porphyrin is used to realize the method for preparing N-tert-butyl benzene sulfonamide by the reaction of weak reactive methyl tert-butyl ether and benzene sulfonamide compound, but the catalyst in the catalytic system has high price and complex preparation, greatly improves the material cost in industrial production and is difficult to popularize and use.

According to the reaction type mechanism, the electron-withdrawing effect of the benzene sulfonamide group exists, and large steric hindrance exists, so that tert-butyl positive ions are easier to eliminate in the reaction, the probability of N-tert-butyl reaction is greatly reduced, and the reaction yield is low.

Disclosure of Invention

Based on the defects of expensive catalyst, low yield and the like in the prior art, the inventor aims to develop an industrial production process for generating N-tert-butyl benzene sulfonamide under the action of the catalyst by taking benzene sulfonamide as a raw material on the basis of the prior work through a large amount of creative labor, solves the problem that tert-butyl ether is poor in reactivity and difficult to use as a reaction raw material, greatly improves the reaction yield, provides a brand new process for synthesizing the compounds, and meets the requirements of industrial production of chemical industry and medicines.

The synthesis method of the N-tert-butyl benzene sulfonamide comprises the following steps: placing the benzene sulfonamide, the material, the catalyst and the solvent into a four-mouth bottle, stirring, heating and refluxing for reaction, obtaining a reaction end point when the benzene sulfonamide serving as a raw material disappears, cooling the reaction product to room temperature, filtering out insoluble substances, and carrying out decompression and desolventization to obtain the N-tert-butyl benzene sulfonamide.

The reaction equation is as follows:

the method for synthesizing the N-tert-butyl benzene sulfonamide adopts a high performance liquid chromatography as a method for judging the reaction end point as the disappearance of the raw material benzene sulfonamide, and comprises the following chromatographic conditions: the ratio of the mobile phase to the methanol-water is 70:30, and the detection wavelength is 254 nm.

According to the synthesis method of the N-tert-butyl benzene sulfonamide, the material is one of tert-butyl acrylate, tert-butyl propionate or tert-butyl alcohol.

According to the synthesis method of the N-tert-butyl benzene sulfonamide, the catalyst is hafnium tetrachloride or zirconium tetrachloride. Preferred catalysts are hafnium tetrachloride;

the synthesis method of the N-tert-butyl benzene sulfonamide comprises the step of using a solvent selected from one of toluene, xylene, dimethyl sulfoxide, diphenyl ether and N-methyl pyrrolidone. The preferred solvent is N-methylpyrrolidone.

According to the synthesis method of the N-tert-butyl benzene sulfonamide, the dosage of the catalyst is 1% -10% of the mass of the benzene sulfonamide. The preferred amount of catalyst is 3% of the mass of benzenesulfonamide.

The synthesis method of the N-tert-butyl benzene sulfonamide has the advantage that the temperature of the heating reflux reaction is 150 ℃.

Compared with the prior art, the synthesis method of the invention has the following technical effects:

the yield of the N-tert-butyl benzene sulfonamide synthesized by the method reaches more than 95.5 percent, and the purity of the N-tert-butyl benzene sulfonamide reaches more than 98 percent. The raw materials adopted by the invention are cheap and easily available, and highly toxic and dangerous raw materials are not used. The catalyst has high activity, low cost and low material cost. The reaction condition is mild, the products are easy to separate, the three industrial wastes are reduced, the method is environment-friendly and meets the requirements of green chemical processes.

Detailed Description

The invention will be further described with reference to specific embodiments for a better understanding of the invention.

Example 1

31.81mmol of benzenesulfonamide, 47.72mmol of tert-butanol and 0.9543mmol of hafnium tetrachloride are added into a four-neck flask with a thermometer and a reflux condenser, 30mL of N-methylpyrrolidone is added as a solvent, the mixture is heated to 150 ℃, the reaction is monitored by HPLC (the chromatographic condition is that the mobile phase ratio is 70:30 methanol-water, the detection wavelength is 254nm), and the disappearance of the raw material benzenesulfonamide is the reaction end point. Cooling the system to room temperature, filtering out insoluble substances, and performing vacuum desolventizing on the filtrate to obtain yellow liquid, namely the product, wherein the yield is 97.5%, the purity is 98.8% (HPLC), and the MS m/z: 213.08(M +1, 100).

Example 2

31.81mmol of benzenesulfonamide, 51.36mmol of tert-butyl propionate and 0.3181mmol of hafnium tetrachloride are added into a four-neck flask with a thermometer and a reflux condenser, 30mL of dimethyl sulfoxide is added as a solvent, the mixture is heated to 139 ℃, HPLC is used for monitoring the reaction (the chromatographic condition is that the mobile phase ratio is 70:30 methanol-water, the detection wavelength is 254nm), and the disappearance of the raw material benzenesulfonamide is the reaction end point. Cooling the system to room temperature, filtering out insoluble substances, and performing vacuum desolventizing on the filtrate to obtain yellow liquid, namely a product, wherein the yield is 96.0%, the purity is 98.8% (HPLC), and the MS m/z: 213.08(M +1, 100).

Example 3

31.81mmol of benzenesulfonamide, 43.18mmol of tert-butyl propionate and 3.181mmol of hafnium tetrachloride are added into a four-neck flask with a thermometer and a reflux condenser, 30mL of xylene is added as a solvent, the mixture is heated to 155 ℃, the reaction is monitored by HPLC (the chromatographic condition is that the mobile phase ratio is 70:30 methanol-water, the detection wavelength is 254nm), and the disappearance of the raw material benzenesulfonamide is the reaction end point. Cooling the system to room temperature, filtering out insoluble substances, and performing vacuum desolventizing on the filtrate to obtain yellow liquid, namely the product, wherein the yield is 95.5%, the purity is 98% (HPLC), and the MS m/z: 213.08(M +1, 100).

Example 4

31.81mmol of benzenesulfonamide, 46.55mmol of tert-butyl acrylate and 2.5448mmol of zirconium tetrachloride are added into a four-neck flask with a thermometer and a reflux condenser, 30mL of diphenyl ether is added, the mixture is heated to 145 ℃, the reaction is monitored by HPLC (the chromatographic condition is that the mobile phase ratio is 70:30 methanol-water, the detection wavelength is 254nm), and the disappearance of the raw material benzenesulfonamide is the reaction end point. Cooling the system to room temperature, filtering out insoluble substances, and performing vacuum desolventizing on the filtrate to obtain yellow liquid, namely the product, wherein the yield is 96.5%, the purity is 98.5% (HPLC), and the MS m/z: 213.08(M +1, 100).

Example 5

31.81mmol of benzenesulfonamide, 47.72mmol of tert-butanol and 1.9086mmol of hafnium tetrachloride are added into a four-neck flask with a thermometer and a reflux condenser, 30mL of N-methylpyrrolidone is added as a solvent, the mixture is heated to 150 ℃, the reaction is monitored by HPLC (the chromatographic condition is that the mobile phase ratio is 70:30 methanol-water, the detection wavelength is 254nm), and the disappearance of the raw material benzenesulfonamide is the reaction end point. Cooling the system to room temperature, filtering out insoluble substances, and performing vacuum desolventizing on the filtrate to obtain yellow liquid, namely the product, wherein the yield is 98.9%, the purity is 99.1% (HPLC), and the MS m/z: 213.08(M +1, 100).

Claims

1. A method for synthesizing N-tert-butyl benzene sulfonamide is characterized by comprising the following steps: placing the benzene sulfonamide, the material, the catalyst and the solvent into a four-mouth bottle, stirring, heating and refluxing for reaction, wherein the reaction end point is obtained when the benzene sulfonamide serving as a raw material disappears, obtaining a reactant, cooling the reactant to room temperature, filtering out insoluble substances, and carrying out decompression and desolventizing to obtain N-tert-butyl benzene sulfonamide;

the material is tert-butyl acrylate or tert-butyl propionate;

the catalyst is hafnium tetrachloride or zirconium tetrachloride;

the solvent is N-methyl pyrrolidone;

the temperature of the heating reflux reaction was 150 ℃.

2. The method for synthesizing N-tert-butylbenzenesulfonamide according to claim 1, wherein the determination method that the disappearance of the raw material benzenesulfonamide is the reaction end point is a determination method by adopting a high performance liquid chromatography, and the chromatographic conditions are as follows: the ratio of the mobile phase to the methanol-water is 70:30, and the detection wavelength is 254 nm.

3. The method of synthesizing N-tert-butylbenzenesulfonamide according to claim 1, wherein said catalyst is hafnium tetrachloride.

4. The method for synthesizing N-tert-butylbenzenesulfonamide according to any one of claims 1 to 3, wherein the amount of the catalyst is 1 to 10% of the mass of the benzenesulfonamide.

5. The method for synthesizing N-tert-butylbenzenesulfonamide according to claim 4, wherein the amount of the catalyst is 3% of the mass of the benzenesulfonamide.