Job/Unit: O50050
/KAP1
Date: 24-02-15 17:02:30
Pages: 7
Facile Arene Hydrogenation under Flow Conditions
gle pass of the reaction solution through the catalyst car- N. E. Chemcat Corporation are highly appreciated. The authors
thank ThalesNano Nanotechnology, Inc. for packing the catalysts
in the 30 mm long cartridges (CatCarts). Zeon Corporation
tridge (single-pass process, ca. 0.3 mL inside volume and
1
mL/min flow rate). In addition, the 10% Rh/C or 10%
(Tokyo, Japan) is thanked for a kind gift of cyclopentyl methyl
Ru/C never degraded during the present study, and the rho-
dium metal never leached into the reaction solution. The
present study will add a new process for easy and practical
access to alicyclic compounds.
ether (CPME). T. H. is grateful to the Japan Science Society for a
Sasakawa Scientific Research Grant and for partial financial sup-
port of this study.
[
[
1] S. Nishimura, Handbook of Heterogeneous Catalytic Hydrogen-
ation for Organic Synthesis Wiley, New York, 2001, p. 414–496.
2] a) I. S. Park, M. S. Kown, N. Kim, J. S. Lee, K. Y. Kang, J.
Park, Chem. Commun. 2005, 5667–5669; b) K. H. Park, K.
Jang, H. J. Kim, S. U. Son, Angew. Chem. Int. Ed. 2007, 46,
Experimental Section
General Comments: All reagents and solvents were obtained from
commercial sources and used without further purification. The
1152–1155; Angew. Chem. 2007, 119, 1170–1173; c) B. Léger,
10% Rh/C (dry type) and 10% Ru/C (dry type) were obtained from
A. Denicourt-Nowicki, H. Olivier-Bourbigou, A. Roucoux,
ChemSusChem 2008, 1, 984–987; d) B. A. Kakade, S. Sahoo,
S. B. Halligudi, V. K. Pillai, J. Phys. Chem. C 2008, 112, 13317–
13319; e) L. Barthe, A. Denicourt-Nowicki, A. Roucoux, K.
Philippot, B. Caudret, M. Hemati, Catal. Commun. 2009, 10,
1235–1239; f) G. Falini, A. Gualandi, D. Savoia, Synthesis
N.E. Chemcat Corporation (Tokyo, Japan) and packed in 30 mm
long cartridges (CatCarts) at ThalesNano Nanotechnology, Inc.
(
Budapest, Hungary). All reactions were performed with the H-
®
Cube continuous-flow hydrogenation reactor (H-Cube SS, Thales-
1
13
Nano Nanotechnology, Inc.). The H and C NMR spectra were
recorded with a JEOL JMN AL-400 spectrometer (400 MHz for
2009, 2440–2446; g) Y. Motoyama, M. Takasaki, S.-H. Yoon,
I. Mochida, H. Nagashima, Org. Lett. 2009, 11, 5042–5045; h)
C. Hubert, A. Denicourt-Nowicki, P. Beaunier, A. Roucoux,
Green Chem. 2010, 12, 1167–1170; i) S. A. Stratton, K. L. Lu-
ska, A. Moores, Catal. Today 2012, 183, 96–100; j) C. Hubert,
E. G. Bilé, A. Denicourt-Nowicki, A. Roucoux, Green Chem.
2011, 13, 1766–1771; k) S. Niembro, S. Donnici, A. Shafir, A.
Vallribera, M. L. Buil, M. A. Esteruelas, C. Larramona, New
J. Chem. 2013, 37, 278–282.
1
13
H NMR and 100 MHz for C NMR) with CDCl
The chemical shifts (δ) are expressed in ppm and internally refer-
enced (δ = 0.00 ppm for tetramethylsilane/CDCl ). The mass spec-
3
as the solvent.
3
tra (EI) were recorded with a JEOL JMS Q1000GC Mk II Quad
GC–MS instrument. The spectroscopic data for all products were
identical to those reported previously.
Typical Procedure for the 10% Rh/C-Catalyzed or 10% Ru/C-Cata-
lyzed Arene Hydrogenations under Flow Conditions (Table 3 and
Table 4): A solution of the substrate (1.00 mmol) in iPrOH (20 mL)
was pumped at 1 mL/min into the catalyst-packed cartridge [10%
Rh/C (99.1 mg) or 10% Ru/C (94.0 mg); 30 mm long cartridge, ca.
[3] K. X. Yao, X. Liu, Z. Li, C. C. Li, H. C. Zeng, Y. Han, Chem-
CatChem 2012, 4, 1938–1942.
[4] T. Maegawa, A. Akashi, K. Yaguchi, Y. Iwasaki, M. Shigetura,
Y. Monguchi, H. Sajiki, Chem. Eur. J. 2009, 15, 6953–6963.
[
5] For reviews, see: a) Chemical Reactions and Processes under
Flow Conditions (Eds.: S. V. Luis, E. Garcia-Verdugo), RSC
Publishing, Cambridge, 2010; b) M. Irfan, T. N. Glasnov, C. O.
Kappe, ChemSusChem 2011, 4, 300–316; c) J. Wegner, S. Cey-
lan, A. Kirschning, Adv. Synth. Catal. 2012, 354, 17–57; d)
I. R. Baxendale, J. Chem. Technol. Biotechnol. 2013, 88, 519–
0.3 mL volume] under 1 or 50 bar hydrogen pressure at 25, 50, 75,
or 100 °C after the flow of iPrOH and hydrogen to the cartridge
under the same conditions for ca. 10 min. The whole reaction mix-
ture was collected and concentrated in vacuo to give the corre-
sponding hydrogenated product. If necessary, the product was fur-
ther purified by silica gel column chromatography (hexane/EtOAc).
The NMR spectroscopic data of the obtained product were iden-
tical to those reported previously; see Supporting Information.
552; e) J. C. Pastre, D. L. Browne, S. V. Ley, Chem. Soc. Rev.
2013, 42, 8849–8869.
[6] For the general study of heterogeneous flow hydrogenation,
see: a) A. Sachse, N. Linares, P. Barbaro, F. Fajula, A. Galar-
neau, Dalton Trans. 2013, 42, 1378–1384; b) N. Linares, S.
Hartmann, A. Galarneau, P. Barbaro, ACS Catal. 2012, 2,
2194–2198; c) M. O’Brien, N. Taylor, A. Polyzos, I. R. Baxend-
ale, S. V. Ley, Chem. Sci. 2011, 2, 1250–1257; d) H. Oyamada,
T. Naito, S. Kobayashi, Beilstein J. Org. Chem. 2011, 7, 735–
Scale-Up of the 10% Rh/C-Catalyzed Hydrogenation of Biphenyl
under Flow Conditions: A solution of biphenyl (1.54 g, 10.0 mmol)
in iPrOH (200 mL) was pumped at 1 mL/min into the 10% Rh/C-
packed cartridge under 1 bar hydrogen gas at 25 °C after the flow
of iPrOH and hydrogen to the cartridge under the same conditions
for ca. 10 min. A part of the mixture was concentrated in vacuo,
739; e) M. C. Bryan, D. Wernick, C. D. Hein, J. V. Petersen,
J. W. Eschelbach, E. M. Doherty, Beilstein J. Org. Chem. 2011,
7, 1141–1149; f) F. S. Ekholm, I. M. Mandity, F. Fueloep, R.
Leino, Tetrahedron Lett. 2011, 52, 1839–1841; g) J. J. W.
Bakker, M. M. P. Zieverink, R. W. E. G. Reintjens, F. Kapteijn,
J. A. Moulijn, M. T. Kreutzer, ChemCatChem 2011, 3, 1155–
1
and completion of the reaction was confirmed by H NMR spec-
troscopy. The reaction mixture and the NMR spectroscopy sample
were combined and transferred to a 100 mL volumetric flask.
EtOAc was added to a total volume of 100 mL, and the residual
rhodium species were analyzed by ICP-AES [ICPS-8100 (Shim-
adzu, Kyoto)]. No leaching of rhodium was observed within the
detection limit (Ͻ1 ppm).
1157; h) B. Clapham, N. S. Wilson, M. J. Michmerhuizen, D. P.
Blanchard, D. M. Dingle, T. A. Nemcek, J. Y. Pan, D. R. Sauer,
J. Comb. Chem. 2008, 10, 88–93; i) K. P. Knudsen, J. Holden,
S. V. Ley, M. Ladlow, Adv. Synth. Catal. 2007, 349, 535–538;
j) H. H. Horváth, G. Papp, C. Csajági, F. Joó, Catal. Commun.
2007, 8, 442–446; k) R. V. Jones, L. Godorhazy, N. Varga, D.
Acknowledgments
Szalay, L. Urge, F. Darvas, J. Comb. Chem. 2006, 8, 110–116;
l) V. Franckevicius, K. R. Knudsen, M. Ladlow, D. A. Long-
bottom, S. V. Ley, Synlett 2006, 889–892; m) S. Saaby, K. R.
Knudsen, M. Ladlow, S. V. Ley, Chem. Commun. 2005, 2909–
The authors sincerely thank Dr. Zsolt Lepp and CEO Richard
Jones of ThalesNano Nanotechnology, Inc., and Dr. Yuko
Kawahashi and Mr. Satoshi Ohtsu of Ikeda Scientific Co., Ltd.
2
911; n) S. Saaby, K. R. Knudsen, M. Ladlow, S. V. Ley, Chem.
Commun. 2005, 2909–2911; o) J. Kobayashi, Y. Mori, S. Ko-
bayashi, Chem. Commun. 2005, 2567–2568; p) N. Yoswathan-
anont, K. Nitta, Y. Nishiuchi, M. Sato, Chem. Commun. 2005,
40–42; q) B. Desai, C. O. Kappe, J. Comb. Chem. 2005, 7, 641–
®
(Tokyo, Japan) for their kind assistance and the use of the H-Cube
SS continuous-flow hydrogenator without charge. A kind gift of
0% Rh/C and 10% Ru/C and the ICP-AES measurements by the
1
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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