氨基酸铜螯合物的合成及其催化C-N偶联反应研究  

Synthesis and catalytic C-N coupling reaction of amino acid copper chelates

作　　者：黎敦全 梁伟镔 姚平俊 陈丽贞 黄森 伍熙 傅彦宇 仇江珍 舒绪刚[1] 曾黎燕 LI Dunquan;LIANG Weibin;YAO Pingjun;CHEN Lizhen;HUANG Sen;WU Xi;FU Yanyu;QIU Jiangzhen;SHU Xugang;ZENG Liyan(College of Chemistry and Chemical Engineering,Zhongkai University of Agriculture and Engineering,Guangzhou 510225,China)

机构地区：[1]仲恺农业工程学院化学化工学院,广东广州510225

出　　处：《仲恺农业工程学院学报》2023年第4期67-78,共12页Journal of Zhongkai University of Agriculture and Engineering

基　　金：广东省教育厅大学生创新创业计划项目(202011347073);仲恺农业工程学院年薪制启动项目(KA210319244、KA22016B735)。

摘　　要：为研究氨基酸铜螯合物直接催化C-N偶联反应的效果,设计并合成亮氨酸铜和蛋氨酸铜两个氨基酸铜螯合物.其铜含量分别为亮氨酸铜19.82%和蛋氨酸铜17.57%,与理论值吻合;XRD结果显示亮氨酸铜和蛋氨酸铜分别在2θ角为6.3°和5.6°附近出现衍射主峰,均与文献报导一致,由此确定亮氨酸铜和蛋氨酸铜的结构.将亮氨酸铜和蛋氨酸铜直接用于胺的烃基化C-N偶联反应,20 mol%亮氨酸铜催化下,碘苯与吗啉反应得到目标产物,产率64.7%,高于传统反应体系和蛋氨酸铜催化体系(21.7%).反应拓展到7种芳香烃底物,虽大多中等收率,但碘苯与正丁胺反应产率高达91.4%.进一步用于催化喹唑啉酮的多组分反应,以邻碘苯甲酰胺为原料,5 mol%蛋氨酸铜催化合成2-苯基喹唑啉酮,EtOH回流中产率达到71.2%;以邻溴苯腈为原料,10 mol%蛋氨酸铜催化,100℃DMSO/H2O中产率达到80.5%.研究结果表明,亮氨酸铜更适合催化一步C-N偶联反应,但产率中等偏上,不甚理想;而蛋氨酸铜更适合喹唑啉酮杂环化合物一锅法合成,且具备反应条件温和、催化剂用量低和产率提高等优势.该研究工作证明氨基酸铜螯合物可替代传统的氨基酸+铜反应体系直接用于C-N偶联反应且在多组分反应更有优势.To investigate the catalytic effect of amino-Cu chelates when applying to C-N coupling reaction,leucine-Cu chelate(Leu-Cu)and methionine-Cu chelate(Met-Cu)were synthesized and identified by copper content test that 19.82%for Leu-Cu and 17.57%for Met-Cu,which were consistent with theory values.XRD results showed that the diffracted primary peak at 2θwere 6.3°and 5.6°shown in Leu-Cu and Met-Cu spectrums respectively that were consistent with reported literature.Leu-Cu and Met-Cu were directly applied to catalyze C-N coupling reaction.Both of them gave better results than corresponding amino acid-Cu catalytic system,and Leu-Cu lead to higher yield 64.7%than Met-Cu in one-step C-N coupling reaction(21.7%),and been well substrate tolerated that 7 aryl amines were obtained and yield up to 91.4%in the present of 20 mol%Leu-Cu,but most gave medium yields mostly.However,when applied to one-pot multi-component reaction for the preparation of heterocycle quinazolinone,5 mol%of Met-Cu provided 71.2%yield of expected product starting from 2-iodobenzamide with EtOH as solvent,while 2-iodobenzonitril gave 80.5%yield catalyzed by 10 mol%of Met-Cu under 100℃with DMSO/H 2O as solvent.It was indicated that Leu-Cu gave better results than Met-Cu in one-step C-N coupling reaction,while Met-Cu exhibited mild condition,higher yields and less catalyst amounts compared to traditional amino acid-Cu catalytic system in multi-components reaction.This work certified that amino acid-Cu chelates can replace tradition amino acid+Cu catalyst system in Ullmann C-N coupling reaction,and amino acid-Cu chelates presented better results in multi-component reaction in terms of reaction condition and yield.

关 键 词：氨基酸铜螯合物 Ullmann C-N偶联 蛋氨酸铜 喹唑啉酮 

分 类 号：O627.1[理学—有机化学]