螺[3.4]辛-6-酮的合成研究  

Synthesis of Spiro[3.4]octan-6-one

作　　者：刘斌[1,2] 徐小娜 仝红娟 朱周静 张彦民 LIU Bin;XU Xiaona;TONG Hongjuan;ZHU Zhoujing;ZHANG Yanmin(School of Pharmacy,Shaanxi Institute of International Trade & Commerce,Xi′an 712046,China;Collaborative Innovation Center of Green Manufacturing Technology for Traditional ChineseMedicine in Shaanxi Province,Xi′an 712046,China)

机构地区：[1]陕西国际商贸学院医药学院,陕西西安712046 [2]陕西省中药绿色制造技术协同创新中心,陕西西安712046

出　　处：《化学与生物工程》2019年第6期40-43,共4页Chemistry & Bioengineering

基　　金：陕西省教育厅2018年度专项科研计划项目(18JK0954);陕西国际商贸学院校级项目(SMXY201805);陕西国际商贸学院“中药药效物质研究创新团队”资助项目(SSY18TD01)

摘　　要：在二聚醋酸铑的催化作用下,5-环丁基-2-重氮-3-氧代戊酸甲酯经C-H插入反应得到6-氧代螺[3.4]辛烷-5-羧酸甲酯,再在酸性条件下经脱羧反应得到目标化合物螺[3.4]辛-6-酮;通过 1HNMR和ESI-MS 对中间体及目标化合物的结构进行了确证,并对合成工艺进行了考察。确定C-H插入反应的最佳条件如下:二聚醋酸铑与5-环丁基-2-重氮-3-氧代戊酸甲酯物质的量比为0.05∶1、反应溶剂为二氯甲烷、反应温度为25 ℃、反应时间为2 h;脱羧反应的最佳条件如下:反应温度为70 ℃、反应时间为8 h。在上述条件下,反应总收率达到60.6%。该方法操作简单、收率高,为螺[3.4]辛-6-酮衍生物的合成提供了一种简便有效的途径。Using dirhodium tetraacetate as a catalyst,we synthesized spiro[3.4]octan-6-one by a two-step reaction,which involves the C-H insertion reaction from methyl 5-cyclobutyl-2-diazo-3-oxopentanoate to obtain methyl 6-oxospiro[3.4]octane-5-carboxylate and the decarboxylic reaction of methyl 6-oxospiro[3.4]octane-5-carboxylate in the acid condition.Moreover,we characterized the structure of the intermediates and target compound by 1HNMR and ESI-MS,and investigated the synthesis process.The results show that the optimal C-H insertion reaction conditions are determined as follows:the molar ratio of dirhodium tetraacetate to methyl 5-cyclobutyl-2-diazo-3-oxopentanoate is 0.05∶1,the solvent is dichloromethane,the reaction temperature is 25 ℃,and the reaction time is 2 h;the decarboxylic reaction conditions are determined as follows:the reaction temperature is 70 ℃,and the reaction time is 8 h.Under above conditions,the total yield of spiro[3.4]octan-6-one reaches 60.6%.The method has the advantages of simple operation and high yield,which provides a simple and effective way for the synthesis of spiro[3.4]octan-6-one derivative.

关 键 词：螺[3 4]辛-6-酮 C-H插入反应 脱羧反应 合成 

分 类 号：TQ463[化学工程—制药化工]