以甲醇为碳源的胺类化合物N-甲基化均相催化反应研究进展  

Research progress in homogeneous catalysis of N-methylation of amine using methanol as carbon source

作　　者：王茜 秦雷 郑智平 Qian Wang;Lei Qin;Zhiping Zheng(School of Chemistry and Chemical Engineering,Harbin Institute of Technology,Harbin 150001,China;Department of Chemistry,School of Science,Southern University of Science and Technology,Shenzhen 518055,China)

机构地区：[1]哈尔滨工业大学化工与化学学院,哈尔滨150001 [2]南方科技大学理学院化学系,深圳518055

出　　处：《科学通报》2021年第25期3272-3285,共14页Chinese Science Bulletin

基　　金：南方科技大学科研启动经费及配套经费(Y01216127,Y01216227)、南方科技大学校长卓越博士后计划资助;深圳市南山区特聘专家配套经费(K19219502);广东省催化化学重点实验室(2020B121201002);广东省基础与应用基础研究基金联合基金(2020A1515110990);博士后留(来)深科研资助(K21217515)。

摘　　要：胺类化合物的甲基化反应是一类非常重要的有机反应,被广泛应用于医药、染料、农药和高分子等分子的合成中.传统的甲基化试剂如碘甲烷、硫酸二甲酯、重氮甲烷等毒性较大,而且反应会产生大量的有害废弃物,存在一定弊端.近年来,以金属络合物作为均相催化剂并以甲醇为C1来源的N-甲基化催化反应受到了极大的关注.该反应采用环境友好、价格低廉的甲醇作为甲基化试剂,利用"借氢"机理高效率地实现了芳胺类、脂肪族胺类及磺酰胺类底物的N-甲基化反应.整个过程的副产物只有水,很好地解决了传统方法的缺陷和不足.本文将根据不同金属活性中心(包括钌、铱、铼、铁、锰、钴等)对均相催化剂进行分类,介绍了以甲醇为C1源的伯胺、仲胺及磺酰胺类底物的N-甲基化反应的研究进展.N-methyl substituted amines are important chemicals or valuable intermediates for the production of other end products including pesticides, dyes, drugs, natural products, and polymers. They are typically prepared by N-methylation reactions,starting from parent amines and using methylating reagents such as methyl iodide, diazomethane, and dimethyl sulfate that are frequently hazardous or carcinogenic. Other methods of achieving N-methylation of amines include Eschweiler-Clarke formaldehyde reductive amination, hydrogenation reduction of carbamate, and methylation using dimethyl carbonate, CO2,formic acid, and DMSO as carbon sources. However, these methods involve the use of generally toxic reagents or require harsh reaction conditions, often producing harmful by-products. Moreover, none of these methods have the control toward selective monomethylation or dimethylation. It is therefore desirable and significant to develop new methods with the use of more environmentally friendly methylation reagents and/or reaction conditions for more efficient and selective Nmethylation of amines.Methanol, an easily accessible and inexpensive chemical, has been used as C1 source for a variety of organic transformations, including N-methylation. A commonly accepted mechanism, often referred to as the "hydrogenborrowing" process, entails first dehydrogenation of methanol in the presence of a catalyst to form formaldehyde and the corresponding metal-hydride species, then the reaction of formaldehyde thus produced with an amine of interest to afford an imine intermediate upon the loss of one H2 O molecule, and finally the reaction of the metal-hydride complex with the imine intermediate to afford the N-methylated product. Compared with the method of direct hydrogenation, the "hydrogenborrowing" process is advantageous and practically more attractive due to the mild conditions used, the avoidance of hydrogen gas, and the high atom economy. However, the success of this method hinges upon the activity and selectivity of the accompanied

关 键 词：均相催化 N-甲基化 甲醇 “借氢”机理 C1化学 

分 类 号：O621.251[理学—有机化学]