2,2-二羟甲基-1-氮杂双环[2.2.2]辛-3-酮及其衍生物的合成  

Synthesis of 2,2-bis(hydroxymethyl)-1-azabicyclo[2.2.2] octan-3-one and its derivative

作　　者：何敏焕[1] 项斌[1] 高扬[1] 史津晖[1] 孙宇[1] 

机构地区：[1]浙江工业大学化学工程与材料学院,浙江杭州310032

出　　处：《浙江工业大学学报》2011年第1期34-38,共5页Journal of Zhejiang University of Technology

摘　　要：以4-哌啶甲酸为起始原料,经酯化、N-烃基化、Dieckmann缩合、水解以及Aldol缩合,合成了2,2-二羟甲基-1-氮杂双环[2.2.2]辛-3-酮.探讨了Aldol缩合反应过程中碱用量、福尔马林用量、反应时间、温度等因素的影响,得到了较佳工艺条件:n(碳酸钾)∶n(3-奎宁环酮盐酸盐)=1.1∶1,福尔马林30 mL,反应时间70 min,反应温度50℃,在此条件下,2,2-二羟甲基-1-氮杂双环[2.2.2]辛-3-酮(PRIMA-1)的单步收率为43.5%.PRIMA-1再用丙烯酰氯酯化,合成了其衍生物2,2-二羟甲基-1-氮杂双环[2.2.2]辛-3-酮二丙烯酸酯.产品及中间体经IR,1H-NMR和MS确认.2,2-Bis（hydroxymethyl）-1-azabicyclo[2.2.2]octan-3-one was synthesized from 4-piperidinecarboxylic acid by esterification,N-alkylation,Dieckmann condensation,hydrolysis reaction and Aldol condensation.The influence factors of Aldol condensation such as the amount of base,the amount of formalin,the reaction time and temperature were studied.The optimum reaction conditions were determined as follow： The molar ratio of potassium carbonate to 3-quinuclidinone hydrochloride was 1.1∶1,the amount of formalin was 30 mL,the reaction time was 70 min,the temperature was 50 ℃,the single step yield of 2,2-bis（hydroxymethyl）-1-azabicyclo[2.2.2]octan-3-one（PRIMA-1） was 43.5%.Then 2,2-bis（hydroxymethyl）-1-azabicyclo[2.2.2]octan-3-one diacrylate was synthesized by esterification of PRIMA-1 with acryloyl chloride.The structure of the product was confirmed by IR,1H-NMR and MS.

关 键 词：PRIMA-1 2 2-二羟甲基-1-氮杂双环[2.2.2]辛-3-酮 3-奎宁环酮盐酸盐 2 2-二羟甲基-1-氮杂双环[2.2.2]辛-3-酮二丙烯酸酯 

分 类 号：O626[理学—有机化学]