Preparation method of 2-bromine-3-fluorobenzoic acid

A technology for fluorobenzoic acid and fluorotrifluorotoluene is applied in the field of preparation of 2-bromo-3-fluorobenzoic acid, and achieves the effects of mild process conditions, reasonable process design, and cheap and readily available raw materials

Inactive Publication Date: 2013-01-30
陈卫东
View PDF1 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This route also suffers from the

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 2-bromine-3-fluorobenzoic acid
  • Preparation method of 2-bromine-3-fluorobenzoic acid
  • Preparation method of 2-bromine-3-fluorobenzoic acid

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0031] Example 1, a preparation method of 2-bromo-3-fluorobenzoic acid, the method uses m-fluorobenzotrifluoride as a raw material, through nitration, bromination, reduction, deamination, separation, and hydrolysis to finally obtain the target product 2- Bromo-3-fluorobenzoic acid; its steps are as follows:

[0032] (1) Nitration: Using sulfuric acid as a solvent, m-fluorobenzotrifluoride and nitric acid are subjected to nitration reaction. The molar ratio of m-fluorobenzotrifluoride to nitric acid is 1.0:1.6, and the reaction temperature is 20°C. The reaction produces 4-fluoro- 2-Trifluoromethylnitrobenzene;

[0033] (2) Bromination: Using sulfuric acid as the solvent and dibromohydantoin as the brominating reagent, the molar ratio of 4-fluoro-2-trifluoromethylnitrobenzene to dibromohydantoin is 1.2:1.0, and the reaction temperature The temperature is 20°C; this step of bromination reaction contains two isomers of 3-bromo-4-fluoro-2-trifluoromethylnitrobenzene and 5-bromo-4-fluor...

Example Embodiment

[0038] Example 2, a preparation method of 2-bromo-3-fluorobenzoic acid, the method uses m-fluorobenzotrifluoride as a raw material, through nitration, bromination, reduction, deamination, separation, and hydrolysis to finally obtain the target product 2- Bromo-3-fluorobenzoic acid; its steps are as follows:

[0039] (1) Nitration: Using sulfuric acid as a solvent, m-fluorobenzotrifluoride and nitric acid undergo nitration reaction, wherein the molar ratio of m-fluorobenzotrifluoride to nitric acid is 1.0: 2.0, and the reaction temperature is 30°C. The reaction produces 4-fluoro- 2-Trifluoromethylnitrobenzene;

[0040] (2) Bromination: Using sulfuric acid as the solvent and dibromohydantoin as the brominating reagent, the molar ratio of 4-fluoro-2-trifluoromethylnitrobenzene to dibromohydantoin is 1.4:1.0, and the reaction temperature The temperature is 25°C; this step of bromination reaction produces 3-bromo-4-fluoro-2-trifluoromethylnitrobenzene and 5-bromo-4-fluoro-2-trifluorome...

Example Embodiment

[0045] Example 3, a preparation method of 2-bromo-3-fluorobenzoic acid, the method uses m-fluorobenzotrifluoride as a raw material, through nitration, bromination, reduction, deamination, separation, and hydrolysis to finally obtain the target product 2- Bromo-3-fluorobenzoic acid; its steps are as follows:

[0046] (1) Nitration: Using sulfuric acid as a solvent, m-fluorobenzotrifluoride and nitric acid undergo a nitration reaction, wherein the molar ratio of m-fluorobenzotrifluoride to nitric acid is 1.0:1.8, and the reaction temperature is 25°C. The reaction produces 4-fluoro- 2-Trifluoromethylnitrobenzene;

[0047] (2) Bromination: use sulfuric acid as the solvent and dibromohydantoin as the bromination reagent, in which the molar ratio of 4-fluoro-2-trifluoromethylnitrobenzene to dibromohydantoin is 1.3:1.0, and the reaction temperature The temperature is 22°C; this step of bromination reaction contains two isomers of 3-bromo-4-fluoro-2-trifluoromethylnitrobenzene and 5-bromo...

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 a preparation method of 2-bromine-3-fluorobenzoic acid. According to the method, fluorobenzotrifluoride is used as a material and is subjected to nitration, bromination, reduction, deamination, separation and hydrolysis to finally obtain a target product, namely the 2-bromine-3-fluorobenzoic acid. During the nitration, sulfuric acid is taken as a solvent, and 4-fluorine-2-trifluoromethyl nitrobenzene is obtained after reaction; during the bromination, sulfuric acid is taken as a solvent and dibromohydantoin is taken as a bromination reagent; during the reduction, acetic acid or ammonium chloride is taken as a catalyst in a water phase, and reduced iron powder is used for carrying out reduction reaction; the deamination is carried out in phosphorous acid; during the separation, 2-bromine-3-fluorine trifluorotoluene is obtained by decompression and fractionation of a rectifying column; and the hydrolysis is carried out by adding sulfuric acid to a reaction kettle. The method disclosed by the invention is relatively reasonable in design, low in cost of the material, easy to get the material, and mild, simple and safe in process conditions of the preparation reaction, and the yield is high.

Description

technical field [0001] The invention relates to a method for synthesizing a pharmaceutical intermediate compound, in particular to a method for preparing 2-bromo-3-fluorobenzoic acid. Background technique [0002] 2-Bromo-3-fluorobenzoic acid is a new type of fluorine-containing drug intermediate. Some methods for preparing 2-bromo-3-fluorobenzoic acid and its analogues have been reported in the existing literature: such as PCT Int. Appl., 2008154221, 18 Dec, 2008 reported that 2-amino-3-fluorobenzene Formic acid is used as a raw material, diazotized in hydrobromic acid to obtain the diazonium salt and then reacted with cuprous bromide to obtain the target product, but the preparation of the starting material 2-amino-3-fluorobenzoic acid is very difficult and expensive, resulting in the target Product cost is difficult to reduce. Its reaction scheme is as follows: [0003] [0004] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemist...

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
IPC IPC(8): C07C63/70C07C51/093
CPCC07C51/093C07C63/70
Inventor 陈卫东
Owner 陈卫东
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