Unveiling the mechanism of N‐methylation of indole with dimethylcarbonate using either DABCO or DBU as catalyst

Pedro H. Vendramini; Lucas A. Zeoly; Rodrigo A. Cormanich; Michael Buehl; Marcos N. Eberlin; Bruno R. V.  Ferreira

doi:10.1002/jms.4707

Unveiling the mechanism of N‐methylation of indole with dimethylcarbonate using either DABCO or DBU as catalyst

Pedro H. Vendramini, Lucas A. Zeoly, Rodrigo A. Cormanich, Michael Buehl, Marcos N. Eberlin, Bruno R. V. Ferreira

Research output: Contribution to journal › Article › peer-review

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 or 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 as well as B3LYP‐D3/6‐311+G** calculations suggest that the reaction of DMC with indole under either DABCO or DBU catalysis follow contrasting mechanisms.

Original language	English
Article number	e4707
Journal	Journal of Mass Spectrometry
Volume	56
Issue number	3
DOIs	https://doi.org/10.1002/jms.4707
Publication status	Published - 15 Feb 2021

Keywords

Indole
ESI(+)-MS/MS
N-methylation
Mechanism
Density functional theory

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Vendramini_2021_JMS_DMC_AAM
Copyright © 2021 John Wiley & Sons, Ltd. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1002/jms.4707
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title = "Unveiling the mechanism of N‐methylation of indole with dimethylcarbonate using either DABCO or DBU as catalyst",

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 or 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 as well as B3LYP‐D3/6‐311+G** calculations suggest that the reaction of DMC with indole under either DABCO or DBU catalysis follow contrasting mechanisms.",

keywords = "Indole, ESI(+)-MS/MS, N-methylation, Mechanism, Density functional theory",

author = "Vendramini, {Pedro H.} and Zeoly, {Lucas A.} and Cormanich, {Rodrigo A.} and Michael Buehl and Eberlin, {Marcos N.} and Ferreira, {Bruno R. V.}",

note = "B.R.V.F., P.H.V. and M.N.E. acknowledge the S{\~a}o Paulo State Science Foundation (FAPESP) and the Brazilian National Science Council (CNPq) for financial support. L.A.Z. thanks CNPQ for his PhD scholarship (142476/2018-8), R.A.C. thanks SDumont and CESUP. M.B. thanks the School of Chemistry and EaStCHEM for support and for access to a computer cluster maintained by Dr. H. Fr{\"u}chtl.",

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language = "English",

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T1 - Unveiling the mechanism of N‐methylation of indole with dimethylcarbonate using either DABCO or DBU as catalyst

AU - Vendramini, Pedro H.

AU - Zeoly, Lucas A.

AU - Cormanich, Rodrigo A.

AU - Buehl, Michael

AU - Eberlin, Marcos N.

AU - Ferreira, Bruno R. V.

N1 - B.R.V.F., P.H.V. and M.N.E. acknowledge the São Paulo State Science Foundation (FAPESP) and the Brazilian National Science Council (CNPq) for financial support. L.A.Z. thanks CNPQ for his PhD scholarship (142476/2018-8), R.A.C. thanks SDumont and CESUP. M.B. thanks the School of Chemistry and EaStCHEM for support and for access to a computer cluster maintained by Dr. H. Früchtl.

PY - 2021/2/15

Y1 - 2021/2/15

N2 - 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 or 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 as well as B3LYP‐D3/6‐311+G** calculations suggest that the reaction of DMC with indole under either DABCO or DBU catalysis follow contrasting mechanisms.

AB - 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 or 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 as well as B3LYP‐D3/6‐311+G** calculations suggest that the reaction of DMC with indole under either DABCO or DBU catalysis follow contrasting mechanisms.

KW - Indole

KW - ESI(+)-MS/MS

KW - N-methylation

KW - Mechanism

KW - Density functional theory

U2 - 10.1002/jms.4707

DO - 10.1002/jms.4707

M3 - Article

SN - 1076-5174

VL - 56

JO - Journal of Mass Spectrometry

JF - Journal of Mass Spectrometry

IS - 3

M1 - e4707

ER -

Unveiling the mechanism of N‐methylation of indole with dimethylcarbonate using either DABCO or DBU as catalyst

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Keywords

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