Organic Process Research & Development 2004, 8, 477−481
Continuous Microflow Synthesis of Butyl Cinnamate by a Mizoroki-Heck
Reaction Using a Low-Viscosity Ionic Liquid as the Recycling Reaction Medium
Shifang Liu, Takahide Fukuyama, Masaaki Sato, and Ilhyong Ryu*
Department of Chemistry, Faculty of Arts and Sciences, Osaka Prefecture UniVersity, Sakai, Osaka 599-8531, Japan
Abstract:
probably because heterogeneous catalysis can take advantage
of the high volume-to-surface ratio ensured by the micro-
channels. However, we focus on the potential of this new
technology for use in reactions using homogeneous catalysts.
Ionic liquids are considered to be environmentally benign
alternatives for traditional volatile organic solvents in terms
of their low vapor pressure and tunable miscibility with other
A continuous microflow system was developed with efficient
catalyst recycling for a Mizoroki-Heck reaction of iodobenzene
with butyl acrylate, using a low-viscosity ionic liquid ([bmim]-
2
NTf ) as the reaction medium. Using a CPC CYTOS Lab
System as the microreaction apparatus, in combination with
an originally developed microextraction/catalyst recycling sys-
tem, the reaction medium, which contained Pd catalyst could
be continuously recycled to provide a total of 115.3 g (80%, 10
g/h) of the desired product.
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organic or inorganic chemicals. The immobilization of the
catalyst in the ionic liquid is another attractive advantage of
this new reaction system, since this would facilitate the
separation of both the catalyst and reaction media from the
products. Our interest has focused on the use of a microflow
system in homogeneous catalysis using ionic liquids as the
reaction media. We previously reported on the application
of a microflow system to the Sonogashira coupling reaction
using an ionic liquid, which was particularly useful, when
an IMM micromixer with a channel width of 40 µm was
Introduction
Microreaction (miniaturized chemical reaction) technology
has opened up new perspectives for chemistry and the
chemical industry. Microreactors are expected to have a
1
significant impact on chemical synthesis and production
because of their many advantageous characteristics, such as
highly efficient micromixing, a high volume-to-area ratio,
efficient heat transfer ability, the avoidance of “hot spots”
by effective temperature control, and a high operational
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employed.
If a flow reactor, irrespective of whether it is “micro” or
“
conventional”, was to be applied to a continuous recycling
process, the need to discontinue the reaction because of the
subsequent separation processes after the reaction (extraction
of product from the resulting reaction mixture and separa-
tion), has to be eliminated. The Mizoroki-Heck reaction,6
one of the most useful of the palladium-catalyzed reactions,
has already been carried out successfully in ionic liquids,7
such as 1-butyl-3-methylimidazolium hexafluorophosphate
2
safety. Transition-metal-catalyzed reactions have previously
3
been performed using a microflow system. For example,
hydrogenation, oxidation, Suzuki-Miyaura coupling,
and the Kumada-Corriu reaction have been reported. Most
of them dealt with heterogeneous catalysts, and this is
3a,b
3c,d
3e
3f
*
Author for correspondence. E-mail: ryu@ms.cias.osakafu-u.ac.jp. Tele-
([bmim]PF
6 6
) and ammonium salts. [Bmim]PF functions
phone and fax: +81-72-254-9695.
well, not only for the reaction itself but also for efficient
(
1) (a) Ehrfeld, W.; Hessel, V.; L o¨ we, H. Microreactor: New Technology for
Modern Chemistry; Wiley-VCH: Weinheim, 2000. (b) Jas, G.; Kirschning,
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Baerns, M. Angew. Chem., Int. Ed. 2004, 43, 406.
7a
recovery of the catalyst. Both product and ammonium salts
can be readily separated from the ionic liquid containing Pd
catalyst by successive biphasic workup procedures, and the
Pd catalyst, retained in the ionic liquid, can be recycled
(
2) (a) Skelton, V.; Greenway, G. M.; Haswell, S. J.; Styring, P.; Morgan, D.
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6
(Scheme 1). [Bmim]PF , however, is a highly viscous liquid,
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6
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2
(
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(
G. Synthesis 2003, 2827.
(
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2
001, 1, 164.
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