Gas-liquid and gas-liquid-solid catalysis in a mesh microreactor

Article abstract of DOI:10.1039/b312290e

A microstructured mesh contactor that can offer residence time of more than minutes is used for gas-liquid-solid hydrogenations and gas-liquid asymmetric hydrogenations. Applications for catalyst/chiral inductor screening and for kinetic data acquisition

Full text of DOI:10.1039/b312290e

Gas–liquid and gas–liquid–solid catalysis in a mesh microreactor†
a
a
b
b
a
Radwan Abdallah, Valérie Meille, John Shaw, David Wenn and Claude de Bellefon*
a
Laboratoire de Génie des Procédés Catalytiques, CNRS/ESCPE Lyon, 43 bd. du 11 novembre 1918, 69616
Villeurbanne, France. E-mail: cdb@lgpc.cpe.fr
Bio & Chemical Instrumentation Group, Central Research Laboratories Ltd., Dawley Road, Hayes,
Middlesex, UK UB3 1HH
b
Received (in Cambridge, UK) 3rd October 2003, Accepted 6th January 2004
First published as an Advance Article on the web 22nd January 2004
A microstructured mesh contactor that can offer residence time
of more than minutes is used for gas–liquid–solid hydro-
genations and gas–liquid asymmetric hydrogenations. Applica-
tions for catalyst/chiral inductor screening and for kinetic data
acquisition are demonstrated.
mass transfer limitations vs. chemical regime in multiphase reactors
is to measure activation energy of a known reaction. We have used
the fast Pd/Al or slower Pt/Al catalysed a-methylstyrene
hydrogenation as a test reaction that exhibits, considering the
2
O
3
2 3
O
2
1
conditions of this study, global rate constants of roughly 56 s and
2
1
11a
1
.4 s for the Pd and Pt catalysts respectively.
In this study
Over the past decade, interest has grown in microstructured reactors
due to their potential to conduct mass or heat transfer demanding
reactions under safe conditions while maintaining and/or increasing
methylcyclohexane is fed to the microreactor at a constant rate (0.1
3
21
cm min ) with pulses (100 ml) of a-methylstyrene in methylcy-
clohexane introduced to the flow via an HPLC injection loop. The
product is then collected for 10 min to ensure the sampling of the
entire reacting plug.
1
selectivity and productivity. The small volumes involved and high
heat transfer capabilities allow safe handling of hazardous reactions
or chemicals to be achieved. However, most reports dealing with
microreactors describe reactions involving only one fluid phase, a
liquid for pharmaceutical or speciality chemicals applications or a
gas for heterogeneously catalysed processes.2,3 This stems from
difficulties in ensuring appropriate multiphase contact and mixing.
Thus, only a few reactions involving immiscible fluids, such as
An activation energy of ca. 46 ± 5 kJ mol2 is measured for the
1
Pt catalyst in the mesh microcontactor (Fig. 2). A similar value of
2
1
2 3
39 kJ mol is found for a commercial Pt/Al O powder catalyst in
4
,5
6
fluorination of aromatics, asymmetric hydrogenations, or gas–
7
–9
liquid–solid hydrogenations,
have provided sufficient motiva-
tion for study in microreactors. For example, the exothermic
nitroaromatic hydrogenation has been conducted in a micro-
7
structured falling film reactor, the noble metal catalyst being
deposited on an alumina surface by appropriate impregnation. The
aim of safe and on-demand production was first noted in earlier
8
reports, albeit using less demanding alkene hydrogenations. In that
work, the mass transfer capability of the microfabricated multi-
phase packed-bed reactors was evaluated showing mass transfer
coefficients 1 to 2 orders of magnitude larger than conventional
trickle-bed reactors.
While all reported microreactors were designed for fast reactions
under atmospheric pressure and short reaction time (1–30 s), we felt
that G–L and G–L–S microreactors offering both a large pressure
range and more flexible residence times (10 s to hours) for e.g.
batch operations would be highly desirable.
The fabrication and detailed description of the mesh micro-
1
0
contactor used in this work has been published. The micro-
contactor has two 100 mm deep cavities (100 mL) separated by a
micromesh (Fig. 1). The upper cavity is fed with the reacting gas
hydrogen while the other, the reacting chamber, contains the
reacting liquid. Roughly 20 to 25% of the mesh surface is occupied
by holes of 5 mm diameter which lead to a gas–liquid interfacial
Fig. 1 Drawing of the microstructured mesh contactor and photographs of
the mesh showing the micro-holes (5 mm) (SEM image) and of the mounted
mesh microreactor with fluid connectors.
2
3
2
3
area of ca. 2000 m /m liq well above values (100–300 m /m liq
)
obtained in traditional tank reactors. This design should allow a
good mass transfer between the cavities while stabilising the
interface hence ensuring gas–liquid separation.
For gas–liquid–solid reactions, the bottom glass insert in the
reacting chamber is demountable allowing catalyst coating of
inserts. Inserts used here had porous alumina deposits impregnated
with noble metals and subjected to thermal treatment to provide
well-dispersed metal (ca. 10 mg metal/Al O per insert at 4%
2 3
weight Pt or Pd).
In the first series of experiments, the mass transfer capability of
the mesh microreactor was evaluated. A textbook test to assess
†
Electronic supplementary information (ESI) available: experimental
Fig. 2 Arrhenius plot for the Pd (2) and the Pt ( < ) Al
2 3
O supported
details and literature data. See http://www.rsc.org/suppdata/cc/b3/
b312290e/
catalysts. Conditions: flow mode, 2–3 bar, [a-methylstyrene] 1 M in
3
21
methylcyclohexane, liquid flow rate 0.1 cm min
.
3
72
C h e m . C o m m u n . , 2 0 0 4 , 3 7 2 – 3 7 3
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

a well behaved batch reactor demonstrating chemical regime.† The
activities obtained with the mesh microcontactor are similar to
those observed with the Pt or Pd inserts in the batch reactor which
demonstrates similar mass transfer capabilities for both batch and
micro-reactors.†
On the contrary, for the Pd inserts, the activation energy is close
2
1
to zero in the mesh microreactor whereas it is about 41 kJ mol for
the same catalyst used as a powder in a well-behaved batch
reactor.1 The activity of this catalyst is too high and mass transfer
1a
8
is limiting. A global mass transfer coefficient, in the range K
l
a =
2
1
1–2 s
for the mesh microreactor, can be roughly estimated
applying the “in series mass transfer resistances” concept, and
considering a fast first order reaction. These values are well in
the range of those found in commercial pressure reactors equipped
with baffles and turbines. It further demonstrates the efficiency
of the mesh microreactor where fast mass transfer is achieved
through short ( ~ 100 mm or less) diffusion path lengths.
The second series of experiments deals with the well-known gas–
liquid asymmetric hydrogenation of Z-methylacetamidocinnamate
8
1
1a
1
1b
Fig. 3 Dependence of ee on pressure in a mini batch reactor (2) and in the
mesh microreactor (/). Conditions: [Rh(COD) ]BF /(R,R)-diop; [Rh]
.0001 M, [mac] 0.1 M, 1 min, 20 to 40 °C, MeOH.
2
4
0
Some complexes however are clearly not efficient catalysts for this
reaction (Entries 17–20).
(
mac) with rhodium chiral diphosphine complexes. This class of
reaction is of importance for the life products industry and has been
1
2
A straightforward comparison of activities (conversion vs. time)
with literature data does not hold since many different reaction
conditions have been used.† However, the fairly good agreement
between published and measured ee’s confirms the mesh micro-
reactor’s suitability for catalyst screening (Table 1).
the topic of the 2002 Nobel award. The aim was to demonstrate
the use of the mesh microreactor for ligand or catalyst screening
and process evaluation. The set-up is similar to that used for gas–
liquid–solid operations except that there was no solid catalyst
coating on the glass insert. Also, both the molecular catalyst and the
substrate mac are injected as a mixture in the organic solvent.
Up to 20 chiral diphosphines have been evaluated (Table 1). The
rhodium complexes were prepared as stock solutions by mixing the
The influence of the hydrogen pressure on the ee is a well known
phenomenon in asymmetric hydrogenation that is an issue for both
industrial processes and academic research.13 This phenomenon
can be efficiently investigated using the mesh microreactor as
demonstrated by comparison with data obtained using a mini-batch
[
2 4
Rh(COD) ]BF precursor and the diphosphine using Schlenck
techniques with the exception of the commercially available Rh/
Binap and Rh/Dipamp catalysts (entries 2 & 15).
3
6b,11b
pressure reactor (25 cm , Parr)
(Fig. 3).
In conclusion, the mesh microreactor presented here allows the
accurate investigation of fast gas–liquid and gas–liquid–solid
catalytic reactions and can also be used for screening applications
with chiral ligand inventory down to 10 nmole.
This research was supported by the European Commission
through the KEMICC project (GRD-2000-256262). Professor
Julian Ross and Dr Serguei Belochapkine from Limerick Uni-
versity are warmly acknowledged for the alumina washcoat
deposition.
Mesh microreactor tests can be applied to very active catalysts
such as the Rh/diop complex by operation in the continuous or flow
mode enabling short residence times (1 min) (Entry 1a). When
longer residence times are required, the mesh microreactor can be
operated batchwise by interrupting the liquid flow using appro-
priate valves. For example, the conversion obtained with the Rh/
Me-Duphos catalyst rises from 31% to 76% upon raising the
residence time from 1 min (flow) to 30 min (batch). For the very
active Rh/diop catalyst, no further conversion nor enantiomeric
excess (ee) change is observed under batch operation (entry 1b).
Data of this type aid evaluation of catalyst stability or deactivation.
Notes and references
Table 1 Screening of 20 chiral diphosphine ligands for the hydrogenation of
Z-methylacetamidocinnamate (mac)
1 W. Ehrfeld, V. Hessel and H. Löwe, Microreactors, Wiley-VCH,
Weinheim, 2000.
2
3
P. D. I. Fletchar, S. J. Haswell, E. Pombo-Villar, B. H. Warrington, P.
Watts, S. Y. F. Wong and H. Zhang, Tetrahedron, 2002, 58, 4735.
A. Gravilidis, P. Angeli, E. Cao, K. K. Yeong and Y. S. S. Wan, Chem.
Eng. Res. Des., 2002, 80, 3.
Entry Chiral ligand
Operationa Conv. ee
ee lit.b
67
1
1
2
3
4
4
5
6
7
8
9
0
1
2
3
4
a
b
(R,R)-Diop
(R,R)-Diop
Flow
Batch
Flow
Flow
Flow
Batch
Flow
Flow
Flow
Flow
Flow
Flow
Batch
Batch
Batch
Batch
> 98
> 96
54
41
31
76
35
32
9
61
62
62
4 K. Jahnisch, M. Baerns, V. Hessel, W. Ehrfeld, V. Haverkamp, H.
Lowe, Ch. Wille and A. Guber, J. Fluorine Chem., 2000, 105, 117.
5 N. de Mas, A. Guenther, M. A. Schmidt and K. F. Jensen, Ind. Eng.
Chem. Res., 2003, 42, 698.
6 (a) C. de Bellefon, N. Tanchoux, S. Caravieilhes, P. Grenouillet and V.
Hessel, Angew. Chem., Int. Ed., 2000, 39, 3442; (b) C. de Bellefon, N.
Pestre, T. Lamouille, P. Grenouillet and V. Hessel, Adv. Synth. Catal.,
2003, 345, 190.
7 K. K. Yeong, A. Graviilidis, R. Zapf and V. Hessel, Catal. Today, 2003,
81, 641.
8 M. W. Losey, M. A. Schmidt and K. F. Jensen, Ind. Eng. Chem. Res.,
2001, 40, 2555.
[Rh((R)-Binap)(COD)]+
(R,S)-Cy-Cy-Josiphos
(R,R)-Me-Duphos
(R,R)-Me-Duphos
(R,S)-Josiphos
93
70
a
b
> 98
95
98
87
89
59
81
96
93
(S,S)-BPPM
(R,S)-Cy-Ph-Josiphos
(R)-Prophos
(R,S)-Ph-tBu-Josiphos
(R,R)-Trost ligand
(S,S)-BDPP
Carbophos
(R,R)-Me-BPE
(R,R)-Et-Duphos
9
5
31
1
1
1
1
1
< 1 n.d.
79
61
53
45
71
80
87
87
9 R. Födisch, D. Hönicke, Y. Xu and B. Platzer, in Microreaction
Technology, Eds. M. Matlosz, W. Ehrfeld, J. P. Baselt, Springer, Berlin,
2002, p. 408.
85
99
[
Rh((R,R)-
10 D. A. Wenn, J. E. A. Shaw and B. Mackenzie, Lab on a Chip, 2003, 3,
180.
+
15
16
17
18
19
20
a
Dipamp)(COD)]
(R,R)-Et-BPE
(S,S)-Chiraphos
(S)-NMDPP
(R,R)-Norphos
(R)-Quinap
Batch
Batch
Batch
Batch
Batch
Batch
34
25
12
11
10
263 292
84
84
93
11 (a) V. Meille, C. de Bellefon and D. Schweich, Ind. Chem. Eng. Res.,
2002, 41, 1711; (b) V. Meille, N. Pestre, P. Fongarland and C. de
Bellefon, Ind. Chem. Eng. Res., DOI: 10.1021/ie030569j.
12 Many examples can be found in Handbook of asymmetric catalysis, E.
N. Jacobsen, A. Pfaltz and H. Yamamoto, Eds., Springer, Berlin,
2000.
60
251
237
< 4
Flow and Batch modes see text. Reaction conditions see Fig. 3. b For
literature data see Electronic Supplementary Information.†
1
3 R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New
York, 1994, p. 33.
C h e m . C o m m u n . , 2 0 0 4 , 3 7 2 – 3 7 3
373