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

Synthesis method of rhein and Diacerein

A diacerein and cyclization technology, which is applied in the field of improved synthesis of antipyretic and analgesic drugs and intermediate chrysophanol, can solve the problems of high price of hydroiodic acid, difficulty in separation and purification, human and environmental pollution, etc., and achieve Improvement of purity and color, high product yield and good purity

Inactive Publication Date: 2007-02-07
NAN JING RHINE PHARM TECH
View PDF0 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are isomers during cyclization by this method, and it is difficult to separate and purify
[0012] (3) Halogenated quinone method, ①Gerard.Lang et al. (U.S.3773801, 1973) use 2-bromo-5-chloro-8-hydroxyquinone and 1,1-diethoxy-3-methylbutadiene to carry out Ernes-Alder reaction, the ethoxylated compound generated by the reaction is deethylated by hydroiodic acid, and chrysophanol is oxidized (aromatized) with chromium trioxide to obtain chrysophanol, but hydroiodic acid is expensive and seriously pollutes people and the environment
But there are 10% isomer by-products during cyclization

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
  • Synthesis method of rhein and Diacerein

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Embodiment 1, the preparation of 2-(2-hydroxyl-4-methylbenzoyl)-3-nitrobenzoic acid

[0023] Weigh 96.6g (0.5mol) of 3-nitrophthalic anhydride and 400g (3.7mol) of m-cresol, and put them into a 2L three-necked flask equipped with a sealed stirrer, anhydrous calcium chloride drying tube and reflux condenser In the process, the flask was cooled in an ice-water bath, and 200g (1.5mol) of powdered anhydrous aluminum trichloride was added at one time, started to stir, heated up, heated to 100-110°C, and stirred vigorously for 3 hours until the release of hydrogen chloride stopped. A thick reddish-brown substance was produced. Ice was added while stirring until the excess chromium trichloride passed through the addition of 150ml of concentrated hydrochloric acid, the product coagulated and the solution was clarified. After filtration, the filter cake was treated with 50 g of sodium carbonate, filtered, and dried to obtain 107.8 g of white crystal 2-(2-hydroxy-4-methylbenzoyl...

Embodiment 2

[0024] Embodiment two, the preparation of 2-(2-hydroxyl-4-methylbenzoyl)-3-aminobenzoic acid

[0025] Put 301 g (1 mol) of 2-(2-hydroxy-4-methylbenzoyl)-3-nitrobenzoic acid, 300 ml of absolute ethanol and 5 g of Raney nickel or 10% palladium carbon into a 1 L autoclave. Close the autoclave, feed hydrogen, raise the temperature to 25°C to make the pressure 20-40Mpa, stir at a medium speed, rapidly raise the temperature to 90°C, stop heating, and maintain the reaction at 90-100°C for 8 hours. Cool, depressurize, and filter the catalyst. Ethanol was distilled off, and the residue was recrystallized to obtain 255 g of the amino compound, with a yield of 94.1%, mp: 225-226° C., and content (HPLC) ≥ 96.5%.

Embodiment 3

[0026] Example 3, Preparation of 1-hydroxyl-8-amino-3-methylanthraquinone

[0027] Put 27.1g (0.1mol) of 2-(2-hydroxy-4-methylbenzoyl)-3-aminobenzoic acid into a 500ml three-neck flask, add strong acid trifluoromethanesulfonic acid or concentrated sulfuric acid and stir to form a suspension , the mixture was heated to 150° C. for two hours, stirred at a constant speed, then the solution was cooled to room temperature, and neutralized with 10% NaOH aqueous solution.

[0028] The precipitate was filtered and evaporated to dryness to obtain a crystalline object, which was recrystallized with acetone and water to obtain about 18.8 g of dark red crystals, with a yield of 78.7%, mp: 245-246°C, and content (HPLC) ≥ 96.0%.

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 provides an improved synthesis method for diacerein, comprising taking 3-nitrophthalic anhydride as the raw material, carrying out a Friedel-Crafts reaction with m-cresol, deoxidizing, cyclizing and diazotizing to obtain an intermediate chrysophanol, then acetylating, and oxidizing to obtain high-purity diacerein with a total yield of 33.7%.

Description

field of invention [0001] The invention relates to the field of organic and medicinal chemistry, in particular, the invention relates to an improved synthesis method of an antipyretic and analgesic drug, diacerein, an osteoarthritis treatment drug, and an intermediate chrysophanol. Background technique [0002] Chrysophanol (rhue root acid, Chrysophanol) and rhein (1,8-dihydroxyanthraquinone-3-carboxylic acid, Rhein) are the main components extracted from the rhizome of the Polygonaceae plant Rheum palmatum, Has antibacterial, anticancer activity and catharsis and diuretic effect. The acetyl derivative of rhein, diacetylrhein (Diacerein), is used in the treatment of rheumatoid and osteoarthritis. Because diacerein is used in the treatment of joint matrix degenerative diseases and connective tissue matrix diseases, rheumatoid arthritis, and also has antipyretic and analgesic effects, it has been valued by the medical and pharmaceutical circles and listed. [0003] [000...

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): C07C50/34C07C46/00
Inventor 陈新梅以成
Owner NAN JING RHINE PHARM 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