Selective N-monomethylation of primary anilines with dimethyl carbonate in continuous flow
Name
Selective N-monomethylation of primary anilines with dimethyl carbonate in continuous flow.pdf
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Author(s)
Seo, Hyowon
Bedard, Anne Catherine
Chen, Willie P.
Hicklin II, Robert William
Alabugin, Alexander
Jamison, Timothy F.
Date Issued
November 2017
Journal
Tetrahedron
Publisher
Elsevier BV
Citation
Seo, Hyowon et al. "Selective N-monomethylation of primary anilines with dimethyl carbonate in continuous flow." Tetrahedron, 74, 25 (June 2018): 3124-3128.
Version
Author's final manuscript
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-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. Keywords: Monomethylation of anilines; Continuous flow chemistry; Green chemistry; Dimethyl carbonate; In situ protection-deprotection
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.tet.2017.11.068
