Study On Synthesis Process Of 2,4-Hexadien-1-ol

2,4-hexadien-1-ol is an important synthetic raw material for the novel anticancer drug AMF-26 and varitriol,and it has very good anticancer activity.AMF-26 acts on the Golgi apparatus in cells.This new therapeutic route was first discovered by Japanese researchers and published in the International Journal of Medicinal Chemistry.Also marine natural product varitriol is toxic to the kidney,central nervous system and breast cancer cell lines.Two natural products reduce the side effects on human health cells under the premise of killing cancer cells.Therefore,the research and development of a mild,green and highly efficient synthetic process of 2,4-hexadien-1-ol is of great significance to pharmaceutical chemists.In this dissertation,sorbic acid was used as raw material to prepare 2,4-hexadien-1-ol.Two routes were used.The first route is to first synthesize sorbic acid methyl sorbate and then use lithium tetrahydroaluminate,sodium borohydride/Lewis,and silicon ether.The second process route is sorbic acid as the starting material,first with ethyl chloroformate synthesis of mixed anhydride form,and then with sodium borohydride dilute aqueous solution reduction,and finally to 2,4-hexadiene-1-ol.This article focuses on the process of synthesis of 2,4-hexadien-1-ol by examining the effects of various process parameters such as equivalence ratio,reaction time,solvent and temperature on the two process routes.Optimization has laid a theoretical foundation for further improving the yield and GC purity of 2,4-hexadien-1-ol,which has important theoretical and practical significance.Through a large number of experimental explorations,it was found that the process route for the preparation of 2,4-hexadien-1-ol was suitable for scale-up experiments.It was reduced by mixed anhydride method and optimized.The final process route is sorbic acid,ethyl chloroformate,triethylamine and sodium borohydride in an equivalent ratio of 1:1:1:2.4.The temperature is 15°C.when ethyl chloroformate is added dropwise,and sodium borohydride diluted alkali solution is added dropwise.The temperature does not exceed-5°C.In this paper,the final amplification of the experiment to a 30L reactor,and the crude product was purified by vacuum distillation.The final product by IR,GC-MS,~1H-NMR analysis of the structure is correct,the experimental yield of up to 74%The GC purity was 93.5%.At the same time,the stability of 2,4-hexadien-1-ol was also studied.It was found that when heated to 30°C,the content was almost constant after 4 h;when heated to 70°C,the content was reduced by about 8%after 4 h;Heating at 100°C,the content decreased by approximately 10%after 4 hours.It is indicated that polymerization may occur under heating conditions,but heating under reduced pressure does not substantially change its content.And such data has not been reported in other literature.