Environment-friendly preparation method of 2 - (4 - Bromomethylphenyl) propionic acid based on two-phase free radical reaction

A bromomethylphenyl, green and environmentally friendly technology, applied in the field of preparation of pharmaceutical intermediates, can solve problems such as pollution, achieve the effects of reducing reaction volume, reducing synthesis costs, and simplifying production processes

Inactive Publication Date: 2013-08-28
FUJIAN SANTAI BIO PHARM +1
View PDF1 Cites 15 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] The problem that the present invention solves is to provide a kind of green environmental protection property method that prepares 2-(4-bromomethylphenyl) propionic acid based on free radical reaction in two

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
  • Environment-friendly preparation method of 2 - (4 - Bromomethylphenyl) propionic acid based on two-phase free radical reaction
  • Environment-friendly preparation method of 2 - (4 - Bromomethylphenyl) propionic acid based on two-phase free radical reaction
  • Environment-friendly preparation method of 2 - (4 - Bromomethylphenyl) propionic acid based on two-phase free radical reaction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Embodiment 1 adopts the green synthesis of the two-phase reaction system of free radical initiator in combination with illumination method as follows:

[0058] Prepare bromine solution in advance as follows: add benzoyl peroxide (BPO, 0.82 g, 3.39 mmol, as a free radical initiator), dichloromethane (45.0 g, 36.0 mL), bromine (9.50g, 3.05mL, 0.059mol), shake to mix well.

[0059] Take 2-(4-methylphenyl)propionic acid (16.4g, 0.10mol) and put it into a three-necked flask equipped with a temperature agent, a reflux condenser and a stirrer, and add dichloromethane (125.3g, 97.4mL ), water (32.8g, 32.8mL), stirring and lowering the temperature to 10-20°C, and then turning on an 80W energy-saving lamp to irradiate the reaction solution;

[0060] Under the condition of 10-20°C, slowly add the pre-prepared bromine solution dropwise, and the rate of addition should be such that the color of the reaction solution is light yellow to reddish. After more than half of the amount of...

Embodiment 2

[0062] Embodiment 2 adopts dichloroethane to replace dichloromethane, and carries out the synthesis of light method combined with free radical initiator

[0063] The basic operation process, the amount of raw materials involved, the light-induced reaction and the post-treatment method are the same as in Example 1, except that the two parts are used as organic solvents for the organic phase. Dichloroethane is used instead of dichloromethane, dichloroethane The amount of dichloroethane used to dissolve 2-(4-methylphenyl)propionic acid is (130.0g, 100.0mL), and the amount of dichloroethane used to dilute bromine is (43.5g, 32.6mL). mp=128.0~130.5℃, the yield is 82.0%, the purity is 98.8%, and the spectral identification data is the same as above.

Embodiment 3

[0064] Embodiment 3 adopts the green synthesis of the two-phase reaction system of direct heating method in conjunction with free radical initiator as follows:

[0065] Pre-constitute the bromine solution as follows: add benzoyl peroxide (BPO, 0.82 g, 3.39 mmol, as a free radical initiator), dichloroethane (43.5 g, 32.6 mL), bromine element (9.50g, 3.05mL, 0.059mol), shake to mix well.

[0066] Get 2-(4-methylphenyl) propionic acid (16.4g, 0.10mol) and put into the three-neck flask that temperature agent, reflux condenser and stirrer are housed, add dichloroethane (130.0g, 100.0 mL), water (32.8g, 32.8mL), appropriate amount of hydrogen peroxide, fully stirred, and after the product was completely dissolved, heated to reflux; at the same time, inject the pre-prepared bromine solution into the constant pressure dropping funnel, and reflux, Slowly add while adding, the rate of addition is preferably when the color of the reaction solution is light yellow to reddish;

[0067] A...

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 an environment-friendly preparation method of 2 - (4 - Bromomethylphenyl) propionic acid based on two-phase free radical reaction, wherein 2 -(4-Bromomethylphenyl) propanoic acid is taken as starting material, and elemental bromine is adopted, and a two phrase mixture reaction system that mixes aqueous phase with organic solvent replaces other reaction systems of single organic solvent; the reaction is initiated by free radical in the two-phase system, or by light or radical initiator; then hydrobromic acid is oxidized with the aid of clean oxidation of hydrogen peroxide so as to get bromine, and the obtained bromine could involve in bromination reaction further, which could obtain 2-(4-bromomethylphenyl) propanoic acid with a better yield and bromide utilization. The product provided by the invention overcomes lots of shortcomings of the existing bromination method, and has the advantages of low cost and environment friendly, and realizes zero pollution in the process of production. Consequently, synthetic process and yield of 2-(4-bromomethylphenyl) propanoic acid are promoted remarkably, and it is very suitable for large scale industrial green production.

Description

technical field [0001] The invention belongs to the technical field of preparation of pharmaceutical intermediates, and relates to a green preparation method for preparing 2-(4-bromomethylphenyl)propionic acid based on free radical reaction in a two-phase system of water phase and organic solvent. Background technique [0002] Loxoprofen sodium (Loxoprofen sodium) is a phenylpropionic acid non-steroidal anti-inflammatory drug developed by Sankyo Co., Ltd. of Japan. Better system tolerance, less toxic side effects (Yamakawa N, Suemasu S, Kimoto A, et al.Low direct cytotoxicity of loxoprofen on gastric mucosal cells[J].Biol.Pharm.Bull.,2010,33(3) , 398-403.). The drug is widely used in arthritis, frozen shoulder, and postoperative anti-inflammatory and analgesic. It has strong antipyretic and analgesic effects, and its curative effect is significantly better than other aryl isopropionic acids such as naproxen, ibuprofen, and ketoprofen. Drugs (Lederman R, Guimaraes S, Verztm...

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): C07C57/58C07C51/363
Inventor 孟歌郑大治张道明王磊范慰超
Owner FUJIAN SANTAI BIO PHARM
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