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Unveiling the mechanism of N ‐methylation of indole with dimethylcarbonate using either DABCO or DBU as catalyst
Author(s) -
Vendramini Pedro H.,
Zeoly Lucas A.,
Cormanich Rodrigo A.,
Buehl Michael,
Eberlin Marcos N.,
Ferreira Bruno R.V.
Publication year - 2021
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.4707
Subject(s) - dabco , chemistry , indole test , octane , catalysis , alkylation , organic chemistry , reaction mechanism , medicinal chemistry , combinatorial chemistry
Depending on the catalyst used, N ‐methylation of indole with dimethylcarbonate (DMC)—an environmentally friendly alkylation agent—yields different products. With 1,4‐diazabicyclo[2.2.2]octane (DABCO), the reaction forms only N ‐methylated indole, but with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU), both N ‐methylated and N ‐methoxycarbonylated indole are formed. Using direct ESI(+)‐MS monitoring to collect actual snapshots of the changing ionic composition of the reaction solution, we report on the interception and characterization of key intermediates for such reactions. Although a mechanism has been proposed with methoxycarbonylated base as the key intermediate for both DBU and DABCO, the ESI(+)‐MS data and B3LYP‐D3/6‐311+G** calculations suggest that the reaction of DMC with indole under either DABCO or DBU catalysis follows contrasting mechanisms.