Synthesis Of α-lipoic Acid

a -lipoic acid is a kind of good antioxidant which is not only applied in clinic, but also widely used in biology, cosmetics and photography. With all these characters, it has highly applied value and broad market prospect.A practical and economical synthesis process has been studied in this paper. With cyclohexanone and ethyl vinyl ether as the starting material, a -Hpoic acid is synthesized via four steps including Free-radical addition, Baeyer-Villiger oxidation, Nucleophilic substitution and Atmospheric oxidation. The yield of the product is about 32%. Furthermore, the reaction system is improved by use of solvent B to produce 6,8-dibromooctanic acid because of the low yield of the third step.The first step is free-radical addition. As the experiment indicates, inert gas promotes the process much and the reaction temperature is 140癈. The substances with low boiling point such as tert-butanol etc are first distilled, and then cyclohexanone is recycled. The recycled cyclohexanone is reused in the first step, and the yield is almost the same.The second step is Baeyer-Villiger oxidation. Whether the process is protected by the inert gas or not, the yield is almost the same. So, a conclusion is drawn from this that the reaction is based on ionic mechanism. The yield of lactone is 91.2%, while the yield of the saponification is 90%.Synthesis of r-lipoic acid is the third step. In accordance with conditions provided by literature, the yield of the experiment done by us was only 31-33%. It's probably because of the long time of cleavage of ether bond. Catalyst A is added to the reaction system so as to accelerate the reaction. The optimizing experiment is done, and the yield is improved to 61.8%.An important reason about the low yield was discovered by the analysis of intermediate and the end product of the third step: the rearrangement of CT. The reaction system is improved by use of solvent B. In the new reaction system, with 8-ethoxy-6-hydroxyoctanoic acid as the starting material, 6,8-dibromooctanoic acid is synthesized by one step, and the yield is about 90%, the purity is 90%.The use of catalyst C has greatly improved the last step which is the synthesis of a -lipoic acid. Methyl tert-butyl ether is added before acidation, and it is added three times with the ratio 10:5:4.