Lipoic Acid Synthesis Process

a -lipoic acid is a kind of medicine,also a kind of good antioxidant which is used in medicine,cosmetics,health-products.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 -lipoic 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%.We seek a new method to synthesize Y -lipoic 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 Y -lipoic acid is the third step. In accordance with the conditions provided by literature, the yield of the experiment done by us was only 31-33%. It's probably because of the difficulty 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 difficulty of synthesis of 6,8-dihalide . We seek a new method to synthesize the Y -lipoic acid, the reaction system is improved by use of solvent B .The form of CT is reduced and the reaction is finished by S\2 mechanism . The yield of the Y -lipoic acid is about 80%, the purity is about 90%.The use of catalyst C has greatly improved the last step in the synthesis of a -lipoic acid. Methyl tert-butyl ether is added before acidification, and it is added three times with the ratio 10:5:4.