Preparation method of (R)-(+)-lipoic acid

Abstract

The invention discloses a preparation method of (R)-(+)-lipoic acid and belongs to the field of organic and medicinal chemistry. The preparation method comprises the following steps: (S)-ethyl 6,8-dichloro caprylate and sulfur are fed into a reaction container equipped with a stirring device, the mixture is heated, an aqueous sodium sulphide solution is added dropwise for a cyclization reaction, heat is preserved, then extraction and concentration are performed, and a cyclization liquid is obtained; the cyclization liquid is fed into the reaction container, an alkaline solution is added, a hydrolysis reaction is performed, and a hydrolysate is obtained through cooling; an organic solvent is added to the hydrolysate, pH is regulated with acid, extraction is performed, an organic layer obtained through extraction is washed to be neutral, then an organic solvent is removed through pressure reduction, a primary product is obtained, a mixed solvent is added to the primary product, the mixture is heated and dissolved, a filter aid is added, stirring and adsorption are performed, filtering is performed, a faint yellow liquid is obtained and cooled, crystals are precipitated, and a finished product is obtained. The steps are reduced, and the preparation efficiency is high; raw material consumption is reduced, the optical rotation of (R)-(+)-lipoic acid reaches 117-118 degrees, the ee value is 99.0%-99.5%, the content is higher than 99%, and waste emission is reduced.

Description

technical field [0001] The invention belongs to the field of organic medicinal chemistry, and in particular relates to a preparation method of R-lipoic acid. Background technique [0002] The aforementioned R-lipoic acid, also known as D-lipoic acid, is a white or light yellow odorless powder or crystal. Optical rotation +120°, Solubility: Insoluble in water, but soluble in benzene, ethanol, chloroform, lipids, etc. The English names of R-lipoic acid are: (R)-(+)-Lipoicacid, (R)-(+)-Thiocticacid and (R)-(+)-1,2Dithiolane-3-pentanoic acid; the chemical name is: ( R)-(+)-1,2-dithiolanyl-3-pentanoic acid and (R)-(+)-5-(1',2'-dithianolyl-3'-)- Valeric acid. [0003] Lipoic acid is a biologically active natural product. In 1951, Raed et al. reported that a crystalline cofactor of a growth-promoting enzyme was isolated from treated insoluble liver tissue residues. Because of its high fat solubility and acidity (pka=4.7), this compound was named sulfur bitter. [0004] R-lipo...

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Problems solved by technology

[0015] The methods for preparing R-lipoic acid in the prior art, including the three methods mentioned above, all have high cost, low yield and large raw material consumption, which cannot meet the requirements of industrialized scale-up production, and are not suitable due to high waste discharge. Disadvantages of meeting the requirements of green technology

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