首页 | 本学科首页   官方微博 | 高级检索  
     检索      


Selective N-monomethylation of primary anilines with dimethyl carbonate in continuous flow
Authors:Hyowon Seo  Anne-Catherine Bédard  Willie P Chen  Robert W Hicklin  Alexander Alabugin  Timothy F Jamison
Institution:Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA
Abstract:Selective N-monomethylation of anilines has been achieved under continuous flow conditions using dimethyl carbonate as a green methylating agent in the presence of 1,8-diazabicyclo5.4.0]undec-7-ene. Our methodology takes advantage of the expanded process windows available in the continuous flow regime to safely induce monomethylation in superheated solvents at high pressure. We propose selective N-monomethylation is achieved via an in situ protection-deprotection pathway, which is supported by the observed reactivities of several putative reaction intermediates. The robust and scalable method was applicable to a broad range of primary aniline substrates including ortho-, meta-, and para-substituted anilines, as well as electron-rich and electron-deficient anilines. The synthetic precursor of diazepam, 5-chloro-2-(methylamino)benzophenone, was selectively synthesized under our optimized conditions.
Keywords:Monomethylation of anilines  Continuous flow chemistry  Green chemistry  Dimethyl carbonate  Corresponding author  
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号