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Are Grignard Reactions in Deep Eutectic Solvents Interface-Driven?

Manasi, Iva ; Bortoli, Marco ; Bowron, Daniel T. ; Campana, Mario ; Hammond, Oliver S. ; Headen, Thomas F. ; Hooton, Jake ; Hevia, Eva ; Cascella, Michele and Eisenstein, Odile , et al. (2025) In Angewandte Chemie - International Edition
Abstract
Due to their high reactivity, organolithium and organomagnesium addition
to ketones is usually performed under inert atmosphere at low
temperature. Recent work has shown that, by dissolving the substrate in
deep eutectic solvents (DES), these processes can be carried out on the
benchtop, in air at room temperature. Surprisingly, the organometallic
reagent, added to the DES from an organic solution, works in these
conditions and gives better yields than in the standard setup. Here, we
investigated acetophenone in a (1:2) choline chloride:glycerol
(ChCl:Gly) DES solution by experimental liquid diffraction, neutron
reflectometry, NMR, interfacial tension measurements, and by
computational... (More)
Due to their high reactivity, organolithium and organomagnesium addition
to ketones is usually performed under inert atmosphere at low
temperature. Recent work has shown that, by dissolving the substrate in
deep eutectic solvents (DES), these processes can be carried out on the
benchtop, in air at room temperature. Surprisingly, the organometallic
reagent, added to the DES from an organic solution, works in these
conditions and gives better yields than in the standard setup. Here, we
investigated acetophenone in a (1:2) choline chloride:glycerol
(ChCl:Gly) DES solution by experimental liquid diffraction, neutron
reflectometry, NMR, interfacial tension measurements, and by
computational modelling. Our data show that this DES is a poor solvent
for the ketone and promotes its accumulation at the surface of the
liquid or its escape into the organic solvent. Molecular dynamics
simulations of Grignard reagent i-PrMgCl in the
(ChCl:Gly)/tetrahydrofuran biphasic system indicate also preference for
its localisation at the interface. These results pinpoint why this
combination of solvents promote the reaction, require stirring, and
accounts for the lack of rapid decomposition of the
organometallic reagents. (Less)
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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Biphasic systems, Green chemistry, Interfacial reactions, Non-volatile solvents, Solvophobic effect
in
Angewandte Chemie - International Edition
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:105014894553
  • pmid:40891084
ISSN
1433-7851
DOI
10.1002/anie.202513649
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.
id
69dc3835-5536-45be-ad59-86cf02697af5
date added to LUP
2025-10-06 15:46:29
date last changed
2025-10-09 10:02:09
@article{69dc3835-5536-45be-ad59-86cf02697af5,
  abstract     = {{Due to their high reactivity, organolithium and organomagnesium addition<br>
 to ketones is usually performed under inert atmosphere at low <br>
temperature. Recent work has shown that, by dissolving the substrate in <br>
deep eutectic solvents (DES), these processes can be carried out on the <br>
benchtop, in air at room temperature. Surprisingly, the organometallic <br>
reagent, added to the DES from an organic solution, works in these <br>
conditions and gives better yields than in the standard setup. Here, we <br>
investigated acetophenone in a (1:2) choline chloride:glycerol <br>
(ChCl:Gly) DES solution by experimental liquid diffraction, neutron <br>
reflectometry, NMR, interfacial tension measurements, and by <br>
computational modelling. Our data show that this DES is a poor solvent <br>
for the ketone and promotes its accumulation at the surface of the <br>
liquid or its escape into the organic solvent. Molecular dynamics <br>
simulations of Grignard reagent <i>i</i>-PrMgCl in the <br>
(ChCl:Gly)/tetrahydrofuran biphasic system indicate also preference for <br>
its localisation at the interface. These results pinpoint why this <br>
combination of solvents promote the reaction, require stirring, and <br>
accounts for the lack of rapid decomposition of the <br>
organometallic reagents.}},
  author       = {{Manasi, Iva and Bortoli, Marco and Bowron, Daniel T. and Campana, Mario and Hammond, Oliver S. and Headen, Thomas F. and Hooton, Jake and Hevia, Eva and Cascella, Michele and Eisenstein, Odile and Edler, Karen J.}},
  issn         = {{1433-7851}},
  keywords     = {{Biphasic systems; Green chemistry; Interfacial reactions; Non-volatile solvents; Solvophobic effect}},
  language     = {{eng}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Angewandte Chemie - International Edition}},
  title        = {{Are Grignard Reactions in Deep Eutectic Solvents Interface-Driven?}},
  url          = {{http://dx.doi.org/10.1002/anie.202513649}},
  doi          = {{10.1002/anie.202513649}},
  year         = {{2025}},
}