Green Synthesis Process Of Key Intermediates Of Idebenone

Cerebrovascular disease is a type of disease that is severely endangering human life and health throughout the world.Traditional treatment schemes can be effectively treated with anticoagulants.In recent years,new brain function-promoting drugs represented by idebenone have been developed.Due to its high-efficiency promoting effect and the advantages of low toxicity and side effects,it has gradually developed It has become the most important method for the treatment of cerebrovascular diseases.Idebenone,chemical name 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone,was marketed in Japan in the late 1980 s and is used to treat ethin A special drug for Ridney Ataxia.Idebenone can improve brain cell func tion clinically,and also has a strong anti-oxidation and scavenging effect on fr ee radicals.It has wide application prospects and market value.This article focuses on the optimization and improvement of the synthesis process of Idebenone,the intermediate of Idebenone,to improve the yield and reduce the route cost.This thesis includes the following parts:The first chapter summarizes the development status and hazards of cerebrovascular diseases,treatment methods,and introduction to the history of idebenone drug development.In the second chapter,the synthetic process of 10-hydroxydecanoic acid is studied.The low-cost castor oil is used as the raw material to obtain10-hydroxydecanoic acid through thermal cracking reaction.During the research,the conditions such as reaction feed ratio,reaction temperature,and reaction time were optimized,and the product was recrystallized and purified.In order to solve the problem of 10-hydroxydecanoic acid central monitoring,this paper chooses to alkylate the product 10-hydroxydecanoic acid first,so that it can be detected by gas chromatography.The purity of the 10-hydroxydecanoic acid obtained in the final reaction is 98%,and the yield is 53.6%,which is higher than the yield of traditional processes by 45%.In Chapter three,the synthesis of Idebenone,an intermediate of Idebenone,is studied.The self-made 10-hydroxydecanoic acid in Chapter two is used as the initial reactant,and the intermediate 10-acetoxy is obtained through acetylation and acyl chloride.The methyldecanoyl chloride is then further reacted with3,4,5-trimethoxytoluene,and the icidol is obtained through a Fockylation reaction,a demethylation reaction,and an alcoholysis reaction.In the optimization process,it was determined that acetic anhydride was used instead of acetic acid as the acetylation reagent,and dichlorosulfoxide was used instead of phosphorus pentachloride as the acid chloride reagent in the literature.The reaction product obtained was easy to purify,and the reaction yield was stable and improved.The effects of reaction feeding method,reaction temperature and reaction time on the reaction were studied in the Fock acylation reaction,demethylation reaction and alcoholysis reaction.Because the self-made 10-hydroxydecanoic acid is used as the starting reactant,the cost of the entire process route is reduced.The total yield of the process route is 52.5%,the purity of the product is 99.7%,and the content of single impurities is less than 0.15%.