铜催化合成氨基异喹啉类化合物

Synthesis of aminoisoquinolines via the copper-catalyzed reaction

氨基异喹啉类化合物是一种非常重要的氮杂环化合物,是多环氮杂芳烃化合物的合成中间体且具有潜在的抗癌活性。在铜催化Ullmann反应的基础上,发展了一种铜催化合成氨基异喹啉类化合物的新方法。该方法采用廉价、易得的2-溴苄胺、丙二腈为底物,CuI作为催化剂,K2CO3为碱,DMF为溶剂,在温和的条件下即可得到目标化合物。反应经历了连续的铜催化下与丙二腈发生N-芳基化反应、分子内关环构建异喹啉环和氧化的过程。所得的产物中含有氨基、氰基,便于对此类活性分子的进一步结构修饰。

Aminoisoquinoline,as an important kind of N-Heterocycles,is a useful intermediate for the synthesis of polycyclic azaaromatic compounds,and has the potential antitumor activity.In this dissertation,we have investigated synthesis of aminoisoquinolines on the base of copper-catalyzed Ullmann reaction.A new,concise and efficient one-pot copper-catalyzed method for synthesis of aminoisoquinolines has been developed.The protocol uses readily available substituted（2-bromophenyl）methanamine,malononitrile as the starting materials,inexpensive CuI as the catalyst,K2CO3 as the base,DMF as the solvent,and the corresponding aminoisoquinolines were obtained under mild conditins.The one-pot reaction underwent sequential couplings of copper-catalyzed intermolecular N-arylation,intramolecular cyclization and oxidation.The synthesized aminoisoquinolines own key functinoal groups including amino and cyano,which provided opportunity for construction of diverse biologically active molecules.