Method for synthesizing ketoprofen by using ethylbenzene as raw material

Abstract

A method for synthesizing ketoprofen from ethylbenzene relates to a preparation method of organic drug, in particular to a method for using ethylbenzene as raw material to synthesize ketoprofen. The inventive method comprises synthesizing o-nitro ethylbenzene and p-nitro ethylbenzene via ethyl benzene, directly processing carboxylation reaction, hydrogenation reduction reaction and benzoylation reaction on the mixture of o-nitro ethylbenzene and p-nitro ethylbenzene without separation, and processing deamination reaction to obtain crude product of ketoprofen, and purifying to obtain the ketoprofen product. The invention directly processes o-nitro ethylbenzene and p-nitro ethylbenzene with cheap carbon dioxide without separation, via carboxylation reaction, while the reaction is safe and environment friend and can save cost. Aminophenyl and benzoyl chloride are directly treated via friedel craft reaction, with less reaction process, low cost, little waste discharge. And the invention uses copper powder as catalyst and uses isopropanol as reducer, thereby saving cost and avoiding the treatment to phosphorus waste water.

Description

technical field [0001] The invention relates to a method for preparing organic medicine, in particular to a method for synthesizing ketoprofen. Background technique [0002] Ketoprofen (Ketoprofen) is a non-steroidal anti-inflammatory analgesic, developed by France Phone-poulenc company, its anti-inflammatory and analgesic effect is stronger and faster than ibuprofen. [0003] Ketoprofen has many synthetic methods, and its representative methods are: [0004] ① Starting from acetophenone, through chloromethylation, benzylation, Daryl condensation, potassium permanganate oxidation, and finally refining to obtain the product, the total yield is about 40%. The chemical reaction formula is as follows: [0005] [0006] 2. "New Synthetic Technology of Ketoprofen" (patent application number 95109877), is to take 2-amino-benzophenone or 4-amino-benzophenone or their amino-protected compounds as starting materials, through α- Halogenated propionylation (or first propionylation ...

AI Technical Summary

Problems solved by technology

[0013] Route ① although the raw material is easy to get, the total yield is low, and the Darzens condensation reaction needs to use a large amount of metallic sodium, which brings great fire hazards to safety production; and the one-step yield and selectivity of potassium permanganate oxidation are not High; in the oxidation process, ketoprofen will be deeply oxidized, resulting in the product having to be refined several times to reach the standard, resulting in a total yield as low as 40%;

[0014] Route ② also has a five-step reaction, and protects and transforms the amino group and the ketone group respectively, resulting in a decrease in the utilization rate of raw materials and an increase in cost;

[0015] Route ③ is actually made ketoprofen by aniline as raw material through 5-step reaction, and diazotization deamination adopts expensive sodium hypophosphite as reducing agent, which has not only increased the cost, but also caused phosphorus-containing wastewater pollution, which is not conducive to Environmental friendly;

[0016] Route ④ has as many as six reaction steps, and requires the use of highly toxic sodium cyanide, and can produce dimethyl products during the methylation process, making the products difficult to refine

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