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

doi:10.1021/jacs.9b00039

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)

^*Corresponding author for this work

Mesoscale Chemical Systems

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

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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 language	English
Pages (from-to)	5369-5380
Number of pages	12
Journal	Journal of the American Chemical Society
Volume	141
Issue number	13
DOIs	https://doi.org/10.1021/jacs.9b00039
Publication status	Published - 3 Apr 2019

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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., Rutjes, F. P. J. T., Gardeniers, H. J. G. E., & 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.

@article{0dd99ad9c4cb468ebcf83ffb12760d15,

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

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.",

author = "{Oosthoek-de Vries}, {Anna Jo} and Nieuwland, {Pieter J.} and Jacob Bart and Kaspar Koch and Janssen, {Johannes W. G.} and {van Bentum}, {P. Jan M.} and Rutjes, {Floris P. J. T.} and Gardeniers, {Han J. G. E.} and Kentgens, {Arno P. M.}",

year = "2019",

month = apr,

day = "3",

doi = "10.1021/jacs.9b00039",

language = "English",

volume = "141",

pages = "5369--5380",

journal = "Journal of the American Chemical Society",

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publisher = "American Chemical Society",

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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 journal › Article › Academic › peer-review

TY - JOUR

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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DO - 10.1021/jacs.9b00039

M3 - Article

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EP - 5380

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 13

ER -