Selective N-monomethylation of primary anilines with dimethyl carbonate in continuous flow

TETRAHEDRON

卷:74

Article

Seo, Hyowon¹  Bedard, Anne-Catherine¹  Chen, Willie P.¹  Hicklin, Robert W.¹  Alabugin, Alexander¹  Jamison, Timothy F.¹ 

[1] MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA

关键词: Monomethylation of anilines;    Continuous flow chemistry;    Green chemistry;    Dimethyl carbonate;    In situ protection-deprotection;   

DOI  :  10.1016/j.tet.2017.11.068

来源: Elsevier

【 摘 要 】

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-diazabicyclo[5.4.0]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. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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