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Mechanistic Insights for Aniline‐Catalyzed Halogenation Reactions
Author(s) -
Qu ZhengWang,
Zhu Hui,
Grimme Stefan
Publication year - 2020
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.202000981
Subject(s) - chemistry , imine , lewis acids and bases , electrophile , protonation , halogenation , aniline , nucleophile , electrophilic aromatic substitution , catalysis , medicinal chemistry , anisole , combinatorial chemistry , organic chemistry , ion
Lewis base catalyzed electrophilic aromatic halogenation using N ‐halosuccinimides (NsX; X=Cl, Br, I) under mild conditions has attracted much attention, but the detailed mechanism remains elusive. Using the aniline MesNH 2 and anisole PhOMe as the typical base catalyst and aromatic substrate, respectively, a novel mechanism is revealed by extensive DFT calculations. The autogenic protonation of imine XMes=NH (via Mes=NH + mediated dimerization of MesNH 2 ) is crucial to initialize the electrophilic halonium X + transfer to nucleophilic substrates. It is shown that the aniline MesNH 2 and more basic imine XMes=NH may act as efficient halonium X + and proton H + shuttles, respectively, connected by the arenium XMesNH 2 + . Non‐coordinating MesNH 3 + salts are suggested as efficient catalyst for electrophilic iodination. Without suitable stabilization of the highly basic anion Ns − , the generally accepted concept of Lewis base catalyst as simple X + shuttle will never work efficiently due to a high thermodynamic barrier. In general, autogenic or additional acid additives should be used for more efficient Lewis base catalyzed halogenation.