Unveiling the mechanism of N-methylation of indole with dimethylcarbonate using either DABCO or DBU as catalyst
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Updated: Nov 17, 2025

Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities
Published on: May 27, 2015
Pedro H Vendramini1, Lucas A Zeoly2, Rodrigo A Cormanich3
1Thomson Mass Spectrometry Laboratory, Institute of Chemistry, University of Campinas-UNICAMP, PO Box 6154, Campinas, São Paulo, 13083-970, Brazil.
Abstract:
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.
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