Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of 3- anilino-2-(3,4,5-trimethoxy benzyl) acrylonitrile

A technology of trimethoxybenzyl and dimethylaminopropionitrile, which is applied in the field of drug synthesis, can solve the problems of high production cost and low yield, and achieve low production cost, high yield and easy industrial scale production Effect

Inactive Publication Date: 2009-11-11
EAST CHINA UNIV OF SCI & TECH
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The purpose of the present invention is to overcome the prior art use of potassium alkoxides to cause high production costs and the use of sodium alkoxides to cause low yields, to provide a low-cost, most simplified 3-anilino-2-(3, The preparation method of 4,5-trimethoxybenzyl)acrylonitrile can realize large-scale industrial production and meet the needs of industrial departments

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of 3- anilino-2-(3,4,5-trimethoxy benzyl) acrylonitrile
  • Preparation method of 3- anilino-2-(3,4,5-trimethoxy benzyl) acrylonitrile
  • Preparation method of 3- anilino-2-(3,4,5-trimethoxy benzyl) acrylonitrile

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Add 250mL of dimethyl sulfoxide, 127.6g of 3-dimethylamine propionitrile (1.30mol) and 11.8g (0.21mol) of potassium hydroxide and 50mL of methanol into a three-necked flask equipped with mechanical stirring. The prepared solution was fully stirred at 45°C for 0.5 hours. At this temperature, 196.2 g of TMB (1.0 mol) was added in batches within 1 hour, then the temperature was raised to 85° C. and the reaction was continued with stirring for 4 hours, followed by thin layer chromatography (TLC) until the spots of TMB raw material disappeared. Cool to 40°C, add 250mL of methanol to stir and dilute under stirring, then add 98.7g of aniline (1.06mol), add 2mol / L dilute sulfuric acid dropwise within 1 hour until the pH is in the range of 3.0-3.5, heat up and reflux for reaction After 2 hours, TLC followed until the 3 spots disappeared. Methanol was distilled off under reduced pressure, 250 mL of water was added, and the reaction mixture was frozen to 3°C. A large amount of ye...

Embodiment 2

[0028] Add 250mL of dimethyl sulfoxide, 127.6g of 2 (1.30mol) and a solution of 11.8g (0.21mol) of potassium hydroxide and 50mL of tert-butanol in sequence in a three-necked flask equipped with mechanical stirring. Stir well for 0.5 hours. At this temperature, 196.2 g of TMB (1.0 mol) was added in batches within 1 hour, then the temperature was raised to 85° C. and the reaction was continued with stirring for 4 hours, followed by TLC until the spots of TMB raw material disappeared. Cool to 40°C, add 250mL of tert-butanol under stirring and dilute, then add 98.7g of aniline (1.06mol), add 2mol / L dilute sulfuric acid dropwise within 1 hour until the pH is in the range of 3.0-3.5, and heat up Reflux reaction for 2 hours, followed by TLC until the spot of 3 disappeared. The tert-butanol was distilled off under reduced pressure, 250 mL of water was added, and the reaction mixture was frozen to 3°C. A large amount of yellow precipitate precipitated and was filtered. The filter cak...

Embodiment 3

[0030] In a three-necked flask equipped with mechanical stirring, 250 mL of dimethyl sulfoxide, 50 mL of methanol, 127.6 g of 2 (1.30 mol), 11.8 g (0.21 mol) of potassium hydroxide and 196.2 g of TMB (1.0 mol) were added successively, The reaction was fully stirred at 80° C. for 5 hours, followed by TLC until the spots of TMB raw material disappeared. Cool to 40°C, add 250mL of methanol to stir and dilute under stirring, then add 98.7g of aniline (1.06mol), add 2mol / L dilute sulfuric acid dropwise within 0.5 hours until the pH is in the range of 3.0-3.5, heat up and reflux for reaction After 2 hours, TLC followed until the 3 spots disappeared. Methanol was distilled off under reduced pressure, 250 mL of water was added, and the reaction mixture was frozen to 3°C. A large amount of yellow precipitate precipitated and was filtered. The filter cake was washed with 500 mL of 15% (v / v) cold ethanol aqueous solution, and 289.3 g of light yellow solid 1 was obtained after vacuum dryin...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a preparation method of 3-anilino-2-(3,4,5-trimethoxy benzyl) acrylonitrile, which comprises the following steps: dissolving acrylonitrile derivative 3-dimethyl amino propionitrile and 3,4,5-trimethoxy benzaldehyde in an aprotic solvent, i.e. dimethyl sulfoxide, and adding a catalytic amount of alcoholic solution of potassium hydroxide; carrying out a first step of condensation reaction to generate 3-dimethylamino-2-(3,4,5-trimethoxy benzyl) acrylonitrile under the condition of heat; diluting the product after the condensation reaction with methyl alcohol, adding aniline with a catalytic amount, fully stirring, dropwise adding one of dilute sulphuric acid, diluted hydrochloric acid or acetic acid in the mixture until the pH value is 0.5-6.5 and heating the mixture for reaction to complete the second step of reaction of replacing dimethylamine functional groups by the aniline; after the reaction, steaming to eliminate the methyl alcohol in the system, freezing the system after adding an appropriate amount of water to 0-5 DEG C, separating out the 3-anilino-2-(3,4,5-trimethoxy benzyl) acrylonitrile which is a yellow solid product, and filtering and drying the product. The invention has the advantages of reasonable technology design, high yield, lower production cost, simple and convenient operation and convenient for mass production in industry.

Description

【Technical field】 [0001] The invention belongs to the technical field of drug synthesis, and relates to a method for preparing the key intermediate 3-anilino-2-(3,4,5-trimethoxybenzyl)acrylonitrile with high yield for preparing the raw material drug trimethoprim. 【Background technique】 [0002] 3-anilino-2-(3,4,5-trimethoxybenzyl)acrylonitrile is a key intermediate in the synthesis of the raw drug trimethoprim (TMP), and TMP is widely used as an antibacterial agent and antibacterial synergist Applied in the medical and animal husbandry industry, 3-anilino-2-(3,4,5-trimethoxybenzyl)acrylonitrile and trimethoprim structural formula are as follows figure 1 shown. [0003] As a classic dihydrofolate reductase inhibitor, TMP has been used for decades, and has been included in the pharmacopoeias of many countries because of its good antibacterial effect and antibacterial synergistic effect. Trimethoprim is an important drug production variety in my country. In recent years, TMP ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07C255/59C07C253/30C07D239/49
CPCY02P20/52
Inventor 冀亚飞万欢方峰段梅莉许煦
Owner EAST CHINA UNIV OF SCI & TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com