1,4,7,10-四氮杂环十二烷的合成方法研究

Synthesis of 1,4,7,10-tetraazacyclododecane(cyclen)

以二乙醇胺和二乙烯三胺为起始原料与对甲苯磺酰氯进行磺酰化反应生成N,O,O′-三(对甲苯磺酰基)双(2-羟乙基)胺和N,N′,N″-三(对甲苯磺酰基)二亚乙基三胺,产率分别为90.0%和92.4%。在无水碳酸钾存在下,100℃加热使所得两种磺酰化产物缩合环化得到1,4,7,10-四(对甲苯磺酰基)-1,4,7,10-四氮杂环十二烷,产率71.0%。然后在浓硫酸作用下,100℃加热脱去对甲苯磺酰基,再以盐酸处理得1,4,7,10-四氮杂环十二烷四盐酸盐,产率85.2%。用核磁共振氢谱对环化产物和目标产物进行了表征。

N,O,O＇-tris（p-toluenesulfonyl） bis（2-hydroxyethyl） amine and N,N＇,N″-tris（p-toluenesulfonyl）-diethylenetriamine were synthesized via the reaction of tosylation with p-toluenesulfonyl chloride,and the yield of target products was 90.0% and 92.4% respectively.The reaction of condensation-cyclization of the two prepared compounds at 100 ℃ in the presence of anhydrous potassium carbonate gave 1,4,7,10-tetrakis（p-toluenesulfonyl）-1,4,7,10-tetraazacyclododecane,with a yield of 71%.Tosyled cyclic amine was heated at 100 ℃ in sulfuric acid to remove p-toluenesulfonyl.After being treated with hydrochloric acid,1,4,7,10-tetraazacyclododecane tetrahydrochloride was formed at a yield of 85.2%.The final product and the intermediate of cyclization were characterized by 1H nuclear magnetic resonance.