1-(5-二茂铁基-1,3,4-噻二唑-2-基)哌啶-2-酮的合成及表征  

Synthesis and characterization of 1-(5-ferrocenyL^(-1),3,4-thiadiazol-2-yl)piperidin-2-one

作　　者：仝红娟 刘斌[1,2] 唐文强 朱周静 TONG Hong-juan;LIU Bin;TANG Wen-qiang;ZHU Zhou-jing(School of Pharmacy,Shaanxi Institute of International Trade&Commerce,Xianyang 712046,China;Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis,Xianyang 712046,China)

机构地区：[1]陕西国际商贸学院医药学院,陕西咸阳712046 [2]咸阳市分子影像与药物合成重点实验室,陕西咸阳712046

出　　处：《化学研究与应用》2023年第6期1330-1335,共6页Chemical Research and Application

基　　金：陕西省高校科协青年人才托举计划项目(20210313)资助;咸阳市分子影像与药物合成重点实验室项目(2021QXNL-PT-0008)资助;陕西省中药绿色制造技术协同创新中心重点培育项目(2019XT-1-03)资助。

摘　　要：本文报道1-(5-二茂铁基-1,3,4-噻二唑-2-基)哌啶-2-酮(1)的合成。首先,在乙酸催化下,二茂铁甲醛(2)和氨基硫脲(3)反应得到二茂铁亚胺基硫脲衍生物(4)。然后,在三氯化铁作用下,中间体4发生关环反应得到5-二茂铁基-1,3,4-噻二唑-2-胺(5)。中间体5再与5-溴戊酰氯(6)发生N-酰基化反应得到5-溴-N-(5-二茂铁基-1,3,4-噻二唑-2-基)戊酰胺(7)。最后,在碱性条件下,中间体7发生分子内关环反应得到目标化合物(1)。中间体及产物结构经1 H NMR、13 C NMR和ESI-MS表征,产物1结构进一步通过X-单晶衍射确证。然后分别考察了中间体5及产物1收率的主要影响因素,确定中间体5合成的适宜条件为:三氯化铁的用量为n(三氯化铁)∶n(中间体4)=4∶1,反应温度80℃,反应时间为15 h,在该条件下,中间体5的收率达到61.9%;确定产物1合成的适宜条件为:反应溶剂为二氧六环,物料比为n(DIEA)∶n(6)∶(5)=3.0∶1.2∶1.0、反应温度为80℃,反应时间为4 h,在该条件下,产物1收率达到68.4%。The synthesis of 1-(5-ferrocenyL^(-1),3,4-thiadiazole-2-yl)piperidin-2-one(1)was reported.First,a ferrocenylidene thiourea derivative(4)was synthesized by the reaction of ferrocenecarboxaldehyde(2)with thiosemicarbazone(3)in the presence of acetic acid.Then,the 5-ferrocenyL^(-1),3,4-thiadiazole-2-amine(5)was obtained by the ring-closing reaction of intermediate 4 in the pres-ence of iron trichloride.The compound 5 through acylation with 5-bromopentanoyl chloride(6)to give 5-bromo-N-(5-ferrocenyL^(-1),3,4-thiadiazol-2-yl)pentanamide(7).Finally,the target compound(1)was obtained by intramolecular ring-closing reaction of intermediate 7 under alkaline conditions.The structures of the intermediates and products were characterized by 1 H NMR,13 C NMR and ESI-MS.The structure of product 1 was further confirmed by X-ray single crystal diffraction.The main factors affecting the yield of intermediate 5 and product 1 were investigated.The optimum conditions for the synthesis of intermediate 5 were as follows:the amount of ferric chloride was n(ferric chloride)∶n(intermediate 4)=4∶1,the reaction temperature was 80℃,and the reaction time was 15 h,under these conditions,the yield of intermediate 5 was 61.9%,and the optimum conditions for the synthesis of prod uct 1 were as follows:the reaction solvent was dioxane,the ratio of materials was n(DIEA)∶n(6)∶n(5)=3.0∶1.2∶1.0,the reaction temperature was 80℃,the reaction time was 4 h,and the reaction temperature was 20℃,under these conditions,the yield of product 1 was 68.4%.

关 键 词：二茂铁 1 3 4-噻二唑 哌啶酮 表征 

分 类 号：O626.2[理学—有机化学]