Inline Reaction Monitoring of Amine-Catalyzed Acetylation of Benzyl Alcohol Using a Microfluidic Stripline Nuclear Magnetic Resonance Setup

Anna Jo Oosthoek-de Vries, Pieter J. Nieuwland, Jacob Bart, Kaspar Koch, Johannes W. G. Janssen, P. Jan M. van Bentum, Floris P. J. T. Rutjes, Han J. G. E. Gardeniers, Arno P. M. Kentgens (Corresponding Author)

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Abstract

We present an in-depth study of the acetylation of benzyl alcohol in the presence of N,N-diisopropylethylamine (DIPEA) by nuclear magnetic resonance (NMR) monitoring of the reaction from 1.5 s to several minutes. We have adapted the NMR setup to be compatible to microreactor technology, scaling down the typical sample volume of commercial NMR probes (500 μL) to a microfluidic stripline setup with 150 nL detection volume. Inline spectra are obtained to monitor the kinetics and unravel the reaction mechanism of this industrially relevant reaction. The experiments are combined with conventional 2D NMR measurements to identify the reaction products. In addition, we replace DIPEA with triethylamine and pyridine to validate the reaction mechanism for different amine catalysts. In all three acetylation reactions, we find that the acetyl ammonium ion is a key intermediate. The formation of ketene is observed during the first minutes of the reaction when tertiary amines were present. The pyridine-catalyzed reaction proceeds via a different mechanism.
Original languageEnglish
Pages (from-to)5369-5380
Number of pages12
JournalJournal of the American Chemical Society
Volume141
Issue number13
DOIs
Publication statusPublished - 3 Apr 2019

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Benzyl Alcohol
Acetylation
Microfluidics
Amines
Alcohols
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
Monitoring
Pyridine
Magnetic resonance measurement
Reaction products
Ammonium Compounds
Ions
Technology
Catalysts
Kinetics
Experiments
pyridine

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Oosthoek-de Vries, A. J., Nieuwland, P. J., Bart, J., Koch, K., Janssen, J. W. G., van Bentum, P. J. M., ... Kentgens, A. P. M. (2019). Inline Reaction Monitoring of Amine-Catalyzed Acetylation of Benzyl Alcohol Using a Microfluidic Stripline Nuclear Magnetic Resonance Setup. Journal of the American Chemical Society, 141(13), 5369-5380. https://doi.org/10.1021/jacs.9b00039
Oosthoek-de Vries, Anna Jo ; Nieuwland, Pieter J. ; Bart, Jacob ; Koch, Kaspar ; Janssen, Johannes W. G. ; van Bentum, P. Jan M. ; Rutjes, Floris P. J. T. ; Gardeniers, Han J. G. E. ; Kentgens, Arno P. M. / Inline Reaction Monitoring of Amine-Catalyzed Acetylation of Benzyl Alcohol Using a Microfluidic Stripline Nuclear Magnetic Resonance Setup. In: Journal of the American Chemical Society. 2019 ; Vol. 141, No. 13. pp. 5369-5380.
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abstract = "We present an in-depth study of the acetylation of benzyl alcohol in the presence of N,N-diisopropylethylamine (DIPEA) by nuclear magnetic resonance (NMR) monitoring of the reaction from 1.5 s to several minutes. We have adapted the NMR setup to be compatible to microreactor technology, scaling down the typical sample volume of commercial NMR probes (500 μL) to a microfluidic stripline setup with 150 nL detection volume. Inline spectra are obtained to monitor the kinetics and unravel the reaction mechanism of this industrially relevant reaction. The experiments are combined with conventional 2D NMR measurements to identify the reaction products. In addition, we replace DIPEA with triethylamine and pyridine to validate the reaction mechanism for different amine catalysts. In all three acetylation reactions, we find that the acetyl ammonium ion is a key intermediate. The formation of ketene is observed during the first minutes of the reaction when tertiary amines were present. The pyridine-catalyzed reaction proceeds via a different mechanism.",
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Oosthoek-de Vries, AJ, Nieuwland, PJ, Bart, J, Koch, K, Janssen, JWG, van Bentum, PJM, Rutjes, FPJT, Gardeniers, HJGE & Kentgens, APM 2019, 'Inline Reaction Monitoring of Amine-Catalyzed Acetylation of Benzyl Alcohol Using a Microfluidic Stripline Nuclear Magnetic Resonance Setup' Journal of the American Chemical Society, vol. 141, no. 13, pp. 5369-5380. https://doi.org/10.1021/jacs.9b00039

Inline Reaction Monitoring of Amine-Catalyzed Acetylation of Benzyl Alcohol Using a Microfluidic Stripline Nuclear Magnetic Resonance Setup. / Oosthoek-de Vries, Anna Jo; Nieuwland, Pieter J.; Bart, Jacob; Koch, Kaspar; Janssen, Johannes W. G.; van Bentum, P. Jan M.; Rutjes, Floris P. J. T.; Gardeniers, Han J. G. E.; Kentgens, Arno P. M. (Corresponding Author).

In: Journal of the American Chemical Society, Vol. 141, No. 13, 03.04.2019, p. 5369-5380.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Inline Reaction Monitoring of Amine-Catalyzed Acetylation of Benzyl Alcohol Using a Microfluidic Stripline Nuclear Magnetic Resonance Setup

AU - Oosthoek-de Vries, Anna Jo

AU - Nieuwland, Pieter J.

AU - Bart, Jacob

AU - Koch, Kaspar

AU - Janssen, Johannes W. G.

AU - van Bentum, P. Jan M.

AU - Rutjes, Floris P. J. T.

AU - Gardeniers, Han J. G. E.

AU - Kentgens, Arno P. M.

PY - 2019/4/3

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N2 - We present an in-depth study of the acetylation of benzyl alcohol in the presence of N,N-diisopropylethylamine (DIPEA) by nuclear magnetic resonance (NMR) monitoring of the reaction from 1.5 s to several minutes. We have adapted the NMR setup to be compatible to microreactor technology, scaling down the typical sample volume of commercial NMR probes (500 μL) to a microfluidic stripline setup with 150 nL detection volume. Inline spectra are obtained to monitor the kinetics and unravel the reaction mechanism of this industrially relevant reaction. The experiments are combined with conventional 2D NMR measurements to identify the reaction products. In addition, we replace DIPEA with triethylamine and pyridine to validate the reaction mechanism for different amine catalysts. In all three acetylation reactions, we find that the acetyl ammonium ion is a key intermediate. The formation of ketene is observed during the first minutes of the reaction when tertiary amines were present. The pyridine-catalyzed reaction proceeds via a different mechanism.

AB - We present an in-depth study of the acetylation of benzyl alcohol in the presence of N,N-diisopropylethylamine (DIPEA) by nuclear magnetic resonance (NMR) monitoring of the reaction from 1.5 s to several minutes. We have adapted the NMR setup to be compatible to microreactor technology, scaling down the typical sample volume of commercial NMR probes (500 μL) to a microfluidic stripline setup with 150 nL detection volume. Inline spectra are obtained to monitor the kinetics and unravel the reaction mechanism of this industrially relevant reaction. The experiments are combined with conventional 2D NMR measurements to identify the reaction products. In addition, we replace DIPEA with triethylamine and pyridine to validate the reaction mechanism for different amine catalysts. In all three acetylation reactions, we find that the acetyl ammonium ion is a key intermediate. The formation of ketene is observed during the first minutes of the reaction when tertiary amines were present. The pyridine-catalyzed reaction proceeds via a different mechanism.

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EP - 5380

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

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ER -