Method for synthesizing 5-methyl-2-(2H-1,2,3-triazole) benzoic acid

A synthesis method and technology of benzoic acid are applied in the field of synthesis of 5-methyl-2-benzoic acid, which can solve the problems of low yield, unfavorable industrial production, difficult separation of by-products, expensive starting materials, etc., and achieve low price, The effect of overcoming impurities that are not easy to separate and good economic benefits

Inactive Publication Date: 2018-02-09
SICHUAN UNIV
View PDF1 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are obvious deficiencies in this method: 1) the starting materials are expensive, 2) the by-products produced are not easy to separate, 3) the low yield is not conducive to industrial production
This method also has obvious deficiencies: 1) the reaction route is long, 2) the reactant cuprous cyanide is a highly toxic substance, 3) the yield is low

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
  • Method for synthesizing 5-methyl-2-(2H-1,2,3-triazole) benzoic acid
  • Method for synthesizing 5-methyl-2-(2H-1,2,3-triazole) benzoic acid
  • Method for synthesizing 5-methyl-2-(2H-1,2,3-triazole) benzoic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035]

[0036] Under the protection of argon, add 2-(4-methylphenyl)-2 H -[1,2,3]-Triazole (0.2 mmol), N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) (0.4 mmol), catalyst dichloride (pentamethylcyclopentadienyl) Rhodium (III) dimer ([Cp * RhCl 2 ] 2 (0.01 mmol), the oxidant bistrifluoromethanesulfonate silver imide (AgNTf 2 ) (0.06 mmol), additive sodium acetate (NaOAC) (0.2 mmol), 1,2 dichloroethane (DCE) 2 ml, argon gas exchange three times, and react at 150 ℃ for 48h. After the reaction of the raw materials was detected by TLC, the reaction solution was cooled to room temperature, added with water and dichloromethane for extraction, and the organic phase was retained, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated on a silica gel column to obtain the product Ⅰ , namely 5-methyl-2-(2 H -1,2,3-triazole) benzonitrile, the conversion rate is 95%, and the yield is 81%.

[0037] White solid, mp 84-86 ℃....

Embodiment 2

[0041]Under the protection of argon, add 2-(4-methylphenyl)-2 H -[1,2,3]-Triazole 0.2 mmol, N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) 0.4 mmol, catalyst dichloro(pentamethylcyclopentadienyl)rhodium(III ) dimer ([Cp * RhCl 2 ] 2 )0.01 mmol, oxidant silver sulfate (Ag 2 SO 4 ) 0.06 mmol, additive silver acetate (AgOAC) 0.2 mmol, 1,2 dichloroethane (DCE) 2 ml, argon gas exchanged three times, and reacted at 150 ℃ for 48 h. After the reaction of the raw materials was detected by TLC, the reaction solution was cooled to room temperature, added with water and dichloromethane for extraction, and the organic phase was retained. The organic phase was dried with saturated saline and anhydrous sodium sulfate, concentrated under reduced pressure, and separated on a silica gel column to obtain the product I. That is, 5-methyl-2-(2 H -1,2,3-triazole) benzonitrile, the conversion rate is 87%, and the yield is 77%.

[0042] Compound I was added to 4 moles per liter of potassium hydr...

Embodiment 3

[0044] Under the protection of argon, add 2-(4-methylphenyl)-2H-[1,2,3]-triazole 0.2mmol, N-cyano-N-phenyl-p-toluenesulfonamide into a 15ml sealed tube (NCTS) 0.4mmol, catalyst dichloro(pentamethylcyclopentadienyl) rhodium (III) dimer ([Cp * RhCl 2 ] 2 )0.01mmol, the oxidant bistrifluoromethanesulfonic acid imide silver salt (AgNTf 2 ) 0.06mmol, additive rhodium acetate (Rh(OAC) 2 ) 0.2mmol, 1,2 dichloroethane (DCE) 2ml, three times of argon gas exchange, and react at 150°C for 48h. After the reaction of the raw materials was detected by TLC, the reaction solution was cooled to room temperature, added with water and dichloromethane for extraction, and the organic phase was retained. The organic phase was dried with saturated saline and anhydrous sodium sulfate, concentrated under reduced pressure, and separated on a silica gel column to obtain the product I. That is, 5-methyl-2-(2 H -1,2,3-triazole) benzonitrile, the conversion rate is 92%, and the yield is 76%.

[0045]...

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 relates to synthesis of 5-methyl-2-(2H-1,2,3-triazole) benzoic acid and belongs to the field of organic chemistry. 2-(4-methyl phenyl)-2H-[1,2,3]-triazole serves as a raw material and undergoes tube sealing reaction at 150 DEG C for 48 h with N-cyano-N phenyl para toluene sulfonamide (NCTS) in an organic solvent in which a rhodium catalyst, a silver salt oxidizing agent and an acetate additive are added, and separation is performed, to obtain a compound I; the compound I undergoes heating reflux for 12 h in an alkaline solution, reaction liquid cools to room temperature and the pH is adjusted to 4-5, and a target compound II is obtained after extraction, drying and spin-drying. Compared with the prior art, a method for synthesis of 5-methyl-2-(2H-1,2,3-triazole) benzoic acidis simple to operate, the raw materials are economical, low in toxicity and high in yield; through one step in a C-H activation method, cyano groups are introduced at the second position of 2-(4-methyl phenyl)-2H-[1,2,3]-triazole benzene ring, and 5-methyl-2-(2H-1,2,3-triazole) benzoic acid is obtained by hydrolytic acidification. A reaction path is shortened, and the prepared product is high in purity, has no isomer and has a great application prospect.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry and relates to 5-methyl-2-(2 H The synthetic method of -1,2,3-triazole) benzoic acid. Background technique [0002] Suvorexant is a new drug developed by Merck Pharmaceuticals for the treatment of adult insomnia. It was approved by the US FDA in August 2014. Suvorexant is the first orexin receptor antagonist approved for marketing, which has a new pharmacological mechanism of action and efficacy. [0003] 5-Methyl-2-(2 H -1,2,3-triazole)benzoic acid is an important intermediate for the synthesis of suvorexant. At present, the synthesis of 5-methyl-2-(2 H The method of -1,2,3-triazole)benzoic acid is mainly divided into two kinds, one is to use 3-methyl-6 iodobenzoic acid as raw material, in tetrahydrofuran, N,N-dimethylformamide Under the action of ketone iodide and potassium carbonate in a mixed solvent, react with 1,2,3-triazole to generate 5-methyl-2-(2 H -1,2,3-triazole)benzoi...

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): C07D249/06
CPCC07D249/06
Inventor 吴勇海俐张海龙管玫
Owner SICHUAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap