chemistry on a large preparative scale. At the same time, only
modest scale-up will be required to generate compounds in
quantities appropriate to the industrial production of some
pharmaceuticals and fine chemicals.
We thank Thomas Swan & Co Ltd for fully funding this work
and D. Campbell, S. K. Ross and J. C. Toler for their assistance.
We are grateful to Degussa AG for donating the catalysts. We
thank F. R. Smail, M. W. George, M. Guyler, S. M. Howdle, A.
Kordikowski, K.-H. Pickel, K. Stanley, T. Tacke and S.
Wieland for their help. M. P. thanks the EPSRC/Royal
Academy of Engineering for a Fellowship.
100
90
80
70
60
50
40
30
20
10
0
Footnotes and References
100 120 140 160 180 200 220 240 260 280 300
/ °C
* E-mail: Martyn.Poliakoff@nottingham.ac.uk
T
wall
† The substrate, supercritical fluid and H2 are brought together in a heated
mixer, passed through the reactor containing the catalyst, and then expanded
to separate the product from the fluid and excess H2. The reactor is
assembled from commercially available units: scCO2 and scPropane pump
PM101, H2 compressor CU105 and Expansion Module PE103 (all from
NWA GmbH, Lo¨rrach, Germany), a high pressure mixer (Medimix) and a
Gilson 305 pump (for the organic substrate). Safety note: Flow reactors
have a comparatively small volume under pressure. Nevertheless, equip-
ment with the appropriate pressure and temperature rating should always be
used for high pressure experiments.
‡ Although previous reports have shown that hydrogenation catalysts can be
rather short-lived under supercritical conditions (ref. 11), we have found
that the Deloxan® catalysts (S. Wieland and P. Panster, Catalysis of Organic
Reactions, Marcel Dekker, New York, 1995, p. 383) have survived several
hours under these harsh conditions and can even be used successfully up to
400 °C.
§ The hydrogenation of nitrobenzene itself over a 5% Pt APII Deloxan®
catalyst in scPropane is particularly striking, with conversion of ca. 25% of
the starting material to NH3 and cyclohexane, a reaction which requires
addition of no less than seven H2 molecules to each molecule of
nitrobenzene within a residence time of < 5 min in the reactor (200 °C, 80
bar). By contrast, a 1% Pd APII Deloxan® catalyst gives aniline in 100%
yield under similar conditions.
Fig. 1 Dependence of product distribution on reactor wall temperature for
the hydrogenation of acetophenone 3 in scCO2 with 5% Pd APII Deloxan®
catalyst: (-) 4, (5) 5, ( ~ ) 6 and (!) 7. Reactions were run with flow rates
of 0.5 ml min21 3, 1.0 ml min21 gaseous CO2, and a ratio of H2 :3
increasing from 2:1 to 6:1 at higher temperatures. The total pressure was
held at 120 bar throughout. Product analysis by 1H NMR spectroscopy
(CDCl3).
p = 120 bar) increases the yield of 5 from 44 to 69% at the
expense of 7, or reducing the total pressure (at T = 240 °C and
with constant H2 :3 = 4:1) from 120 to 40 bar (i.e. to the near-
critical region) reduces the degree of hydrogenation, changing
the ratio of products 5:7 from 1:2 to 2:1, presumably by
reducing the residence time. Thus, without changing catalyst,
one can tune conditions to maximise the yield of a particular
product, and the reactor is then sufficiently stable to maintain
those conditions.
The reactor is primarily designed to operate with reactants
and products which are liquids at ambient temperature but it can
also be used to hydrogenate solids, dissolved in an inert organic
solvent. For example, 1,2-(methylenedioxy)-4-nitrobenzene§ 8
(mp 146–148 °C) was hydrogenated quantitatively to 9 in
scCO2 by pumping it through the reactor (ca. 8 g h21) in
MeOH–THF (2:1 v/v) (Scheme 2).
1 C. Y. Tsang and W. B. Streett, J. Eng. Sci., 1981, 36, 993.
2 S. M. Howdle, M. A. Healy and M. Poliakoff, J. Am. Chem. Soc., 1990,
112, 4804.
3 J. W. Rathke, R. J. Klingler and T. R. Krause, Organometallics,
1991,10, 1350.
4 P. G. Jessop, T. Ikariya and R. Noyori, Nature, 1994, 368, 231.
5 P. G. Jessop, Y. Hsiano, T. Ikariya and R. Noyori, J. Am. Chem. Soc.,
1996, 118, 344.
6 M. J. Burk, S. Feng, M. F. Gross and W. Tumas, J. Am. Chem. Soc.,
1995, 117, 8277.
NH2
+ 2 H2O
NO2
+ 3 H2
O
O
O
O
1% Pd Deloxan
140 bar, 90 °C, CO2
quantitative
8
9
Scheme 2
7 B. Minder, T. Mallat, K.-H. Pickel, K. Steiner and A. Baiker, Catal.
Lett., 1995, 34, 1.
The flow reactor can be used to hydrogenate a substantial
range of other organic functional groups. Epoxides, oximes,
nitriles, alcohols and aromatic and aliphatic aldehydes and
ketones have been successfully hydrogenated, most with
conversions comparable to those described above and several
with better selectivity than in non-supercritical hydrogenation.
Most significantly, we have shown that compounds can be
hydrogenated continuously on a relatively large scale using
reactors of very small volume. Thus supercritical fluids can
transform hydrogenation with gaseous H2 into a viable, rapid
8 O. Kro¨cher, R. A. Ko¨ppel and A. Baiker, Chymia, 1997, 51, 48.
9 K.-H. Pickel and K. Steiner, Proc. 3rd Int. Symp. Supercritical Fluids,
Strasbourg, 1994, 3, 25.
10 Roche Magazin, 1992, 41, 2.
11 T. Tacke, S. Wieland and P. Panster, Process Technol. Proc., 1996, 12,
17.
12 M. Ha¨rro¨d and P. Møller, Process Technol. Proc., 1996, 12, 43.
13 J. A. Banister, P. D. Lee and M. Poliakoff, Organometallics, 1995, 14,
3876.
Received in Liverpool, UK, 20th June 1997; 7/04371F
1668
Chem. Commun., 1997