We are grateful to Drs Takehiko Kitamori and Masaharu
Table 1 Hydrogenation reaction
Ueno for helpful discussion. This work was partially supported
by CREST, SORST and ERATO, Japan Science and
Technology Agency (JST), and a Grant-in-Aid for Scientific
Research from Japan Society of the Promotion of Science
(JSPS).
Run
1
Substrate
Product
Yield (%)a
94
Juta Kobayashi, Yuichiro Mori and Shu¯ Kobayashi*
Graduate School of Pharmaceutical Sciences, The University of Tokyo,
Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
E-mail: skobayas@mol.f.u-tokyo.ac.jp; Fax: +81 3 5684 0634;
Tel: +81 3 5841 4790
2
3
96
Quant.
Notes and references
{ The microchannel reactor is a device which has a very small channel
(micrometre-sized in width and depth and centimetre- to metre-sized in
length) in a glass plate.9 A similar device is used mainly in the field of
analytical chemistry.10 One of the most important features of this device is a
large specific interfacial area which rises to 10,000 y 50,000 m2 m23, as
opposed to only 100 m2 m23 for conventional reactors used in chemical
processes.6
4
5
91
92b
6
91
1 M. R. Arnold, Ind. Eng. Chem., 1956, 48, 1629.
2 J. Kobayashi, Y. Mori, K. Okamoto, R. Akiyama, M. Ueno,
T. Kitamori and S. Kobayashi, Science, 2004, 304, 1305.
3 A. Baiker, Chem. Rev., 1999, 99, 453; P. G. Jessop, T. Ikariya and
R. Noyori, Chem. Rev., 1999, 99, 475.
a
b
Isolated yield. NMR yield.
4 R. Akiyama and S. Kobayashi, Angew. Chem. Int. Ed., 2001, 40,
3469.
5 K. Okamoto, R. Akiyama, H. Yoshida, T. Yoshida and S. Kobayashi,
J. Am. Chem. Soc., 2005, 127, 2125.
6 J.-i. Yoshida, Microreactor, Epoch-making Technology for Synthesis,
CMC, Japan, 2000.
triphase microfluidic system2 (from 0.01 mmol h21 per channel to
0.1 mmol h21 per channel), presumably because the solubility of
hydrogen was greatly increased by using scCO2 as a solvent and
mass transfer needed for the reactions occurred smoothly. In
addition to the high reactivity, the system has several practical
advantages. The microchannel reactor was reused several times
without loss of activity. It would be possible to conduct scaled-up
reactions by using a number of channels in parallel.6
7 Some examples of reactions in scH2O using microreactors have been
reported: P. E. Savage and M. A. Smith, Environ. Sci. Technol., 1995,
29, 216; S. P. Maharrey and D. R. Miller, J. Phys. Chem. A, 2001, 105,
5860; Y. Ikushima, K. Hatakeda, M. Sato, O. Sato and M. Arai, Chem.
Commun., 2002, 2208; M. Sasaki, T. Adschiri and K. Arai, J. Agric.
Food Chem., 2003, 51, 5376; Z. Fang, S. Xu, I. S. Butler, R. L. Smith, Jr.
and J. A. Kozinski, Energy Fuels, 2004, 18, 1257; Y. Ikushima and
M. Sato, Chem. Eng. Sci., 2004, 59, 4895.
8 Heat transfer from scCO2 in micro tubes has been investigated:
S. M. Liao and T. S. Zhao, J. Heat Transfer, 2002, 124, 413.
9 Several examples of synthetic organic reactions using microchannel
reactors have been reported: P. D. I. Fletcher, S. J. Haswell, E. Pombo-
Villar, B. H. Warrington, P. Watts, S. Y. F. Wong and X. Zhang,
Tetrahedron, 2002, 58, 4735; K. Ja¨hnisch, V. Hessel, H. Lo¨we and
M. Baerns, Angew. Chem. Int. Ed., 2004, 43, 406; M. Ueno,
H. Hisamoto, T. Kitamori and S. Kobayashi, Chem. Commun., 2003,
936. However, many examples are not efficient enough compared with
those of conventional methods..
In conclusion, we have developed an effective and productive
microfluidic system for hydrogenation reactions using scCO2 as a
solvent.7 To the best our knowledge, this is the first example of the
synthetic application of microchannels using scCO2 as a reaction
medium.8 The reactions proceeded within 1 second by making the
best use of scCO2 as a solvent and utilizing the large surface area of
the catalyst. In addition, high reaction productivity was attained in
each channel. Several practical advantages of this reaction should
also be noted. Further improvement of this system toward
applications to asymmetric catalysis and large-scale synthesis are
now in progress.
10 W. Ehrfeld, V. Hessel and H. Lo¨we, Microreactors, Wiley-VCH,
Weinheim, 2000.
2568 | Chem. Commun., 2005, 2567–2568
This journal is ß The Royal Society of Chemistry 2005