Continuous catalytic "one-pot" multi-step synthesis of 2-ethylhexanal from crotonaldehyde

Article abstract of DOI:10.1039/b710129e

2-Ethylhexanal is synthesized directly from crotonaldehyde over a bifunctional acidic resin-supported palladium catalyst via hydrogenation and aldol condensation in supercritical CO₂. The Royal Society of Chemistry.

Full text of DOI:10.1039/b710129e

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COMMUNICATION
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Continuous catalytic ‘‘one-pot’’ multi-step synthesis of 2-ethylhexanal
from crotonaldehyde{
Tsunetake Seki,{ Jan-Dierk Grunwaldt and Alfons Baiker*
Received (in Cambridge, UK) 3rd July 2007, Accepted 24th July 2007
First published as an Advance Article on the web 6th August 2007
DOI: 10.1039/b710129e
the process has several inherent disadvantages:3b (i) a large excess
2-Ethylhexanal is synthesized directly from crotonaldehyde
amount of CO is required, (ii) the liquid space velocity in the
hydroformylation is relatively low, and (iii) the selectivity to
2-ethylhexanol is rather low. Recently, Kelly and coworkers
developed Pd/Na/SiO2 as a solid base hydrogenation catalyst for
the one-step synthesis of 2-ethylhexanal 4 from 2,3 while Sharma
et al. reported HRhCO(PPh3)3 supported on hydrotalcite as a
novel Aldox catalyst.4 However, with these catalytic systems, the
reactions have to be performed at relatively high temperatures
(350 uC in the former and 200–250 uC in the latter case) owing to
the low reaction rates and the yields of the C8 products are
moderate to low. In addition, several byproducts are formed in
both cases, which renders the product purification troublesome.
Moreover, the Pd/Na/SiO2 catalyst is easily deactivated by
poisoning caused by the product 4.
over a bifunctional acidic resin-supported palladium catalyst via
hydrogenation and aldol condensation in supercritical CO2.
The C8 compounds obtained through the aldol condensation of
butyraldehyde are industrially important and are produced
worldwide on a large scale.1 2-Ethylhexanal, for instance, is used
in disinfectants and insecticides and is employed as a synthetic
intermediate for the manufacture of various organic compounds
such as perfumes, paints, warning agents and leak detectors.
2-Ethylhexanol, 2-ethylhexylamines and 2-ethylhexanoic acid,
which also belong to the class of industrially important C8
chemicals, can be manufactured from this aldehyde by catalytic
hydrogenation, amination and oxidation, respectively.1
An overview of the industrial synthetic routes to the C8
chemicals is shown in Scheme 1. These chemicals are typically
manufactured in several steps, including the hydroformylation of
propylene 1 (step 1), base-catalyzed aldol condensation of
butyraldehyde 2 (step 2) and subsequent gas-phase hydrogenation
of 2-ethylhexenal 3 (step 3).1 The major problem of the
conventional process is that high capital cost plants are required
for product purification, recovery and waste treatment, particu-
larly in the aldol condensation step where homogeneous strong
base catalysts must be handled safely.2 Another drawback is the
high reaction temperature required for the gas-phase hydrogena-
tion. To circumvent these problems, several groups have developed
alternative ‘‘one-pot’’ pathways to the C8 chemicals using 1 or 2
as starting compound. Shell and Exxon developed the ‘‘Aldox
process’’ to produce 2-ethylhexanol from 1 in one step using
co-catalysts in addition to the original ‘‘oxo’’ catalysts.1 However,
We herein report our finding that 2-ethylhexanal 4 can be
synthesized from crotonaldehyde 7 in a one-step continuous
procedure with high conversion and selectivity by using a
palladium-doped acidic resin catalyst§ and supercritical CO2
(scCO2) as
a reaction medium." The only byproduct is
butyraldehyde 2, which is also an industrially important chemical
and easily separated from 4 by distillation due to the large
difference in their boiling points. This new protocol is based on the
efficient palladium–acid bifunctional catalysis5 and the great
miscibity of gaseous hydrogen as well as organic compounds in
scCO2.6,7
Transition-metal supported on an acidic resin of Amberlyst1 15
was first introduced by Laufer and Hoelderich in their research on
the hydroxylation of benzene.5 They loaded not only palladium
but also platinum on the resin and observed an acceleration effect
by the acid sites (sulfonic acid groups). Our initial study on the
hydrogenation of cyclohexene to cyclohexane in scCO2 revealed
that 1% Pd on Amberlyst1 15 is most active for the hydrogenation
of a CLC bond; 0.5% Pd, 2% Pd, a mixture of Pd (0.5%) and Pt
(0.5%), 1% Ru or 1% Rh on the same resin showed much lower
activity.8 Thus we first attempted the one-step production of 4
Department of Chemistry and Applied Biosciences, ETH Zurich,
Ho¨nggerberg, CH-8093 Zurich, Switzerland.
E-mail: baiker@chem.ethz.ch; Fax: +41 1 632 11 63; Tel: +41 1 632 31 53
{ Electronic supplementary information (ESI) available: Experimental
details and the GC profiles. See DOI: 10.1039/b710129e
{ Research Fellow of the Japan Society for the Promotion of Science.
Scheme 1 Overview of the industrial synthetic routes to 2-ethylhexanal (4) and 2-ethylhexanol (X = CH2OH). Reaction type: step 1, hydroformylation;
step 2, aldol condensation; step 3, hydrogenation; step 4, dehydrogenation; step 5, aldol condensation; step 6, hydrogenation.
3562 | Chem. Commun., 2007, 3562–3564
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Table 1 Production of 2-ethylhexanal 4 from crotonaldehyde 7a
Conv.b
(%)
Select. to
4b (%)
Select. to
2b (%)
Entry
Catalyst
1
2
1%
1%
1%
1%
1%
Pd/Cc
94
89
94
98
13
1
47
59
67
55
46
36
32
39
Pd/Amberlyst-15
Pd/Amberlyst-15
Pd/Amberlyst-15
Pd/Amberlyst-15
3d
4e
5f
a
y0
Catalyst, 1.00 g; total pressure, 16 MPa; reactor temperature, 60 uC;
flow rate of fluid, 1 L min21; flow rate of 7, 0.3 mL min21; 7 : H2
1 : 2.0. Determined by GC. Engelhard, 5109; particle size, ca.
0.5–1.4 mm. 7 : H2 = 1 : 3.0. 7 : H2 = 1 : 4.0. Total pressure,
4 MPa; 7 : H2 = 1 : 4.0.
=
b
c
d
e
f
from 2 by using the 1% Pd on Amberlyst1 15 catalyst (denoted 1%
Pd/Amberlyst-15).9 However, GC analysis of the product samples
showed the formation of many unidentified products in consider-
able amounts in addition to 4. We therefore abandoned this
system.
Fig. 1 Variation of the conversion and selectivity with time-on-stream
over 1% Pd/Amberlyst-15. The time started from the first sampling.
Catalyst, 1.00 g; total pressure, 16 MPa; reactor temperature, 60 uC; flow
rate of fluid, 1 L min21; flow rate of 7, 0.3 mL min21; 7 : H2 = 1 : 4.0.
Conversion, $; selectivity to 4, #; selectivity to 2, %; selectivity to 3, e;
selectivity to 1-butanol, n.
We next used crotonaldehyde 7 as starting compound.
Intriguingly, this a,b-unsaturated aldehyde was selectively con-
verted to 2-ethylhexanal 4 and butyraldehyde 2 over 1% Pd/
Amberlyst-15 in scCO2 (Table 1, entries 2–4),10 whereas 1% Pd/C
with no acidity did not afford 4 (entry 1). The product samples
contained a small amount of 2-ethylhexenal 3 besides 4 and 2
when feeding a lower amount of H2. However, the amount of 3
was almost negligible (y0% selectivity) at a 7 : H2 molar ratio of
1 : 4.0 and the 4 + 2 selectivity achieved was almost 100% (entry 4).
Increasing the amount of H2 in the feed also led to an increase of
conversion and selectivity to the target product 4. Note that 1%
Pd/Amberlyst-15 gave 1-butanol in a quite low selectivity of 1%
and did not afford 2-ethylhexanol under the conditions of entries
2–4, while 1% Pd/C afforded 1-butanol in a higher selectivity of
9%, indicating that 1% Pd/Amberlyst-15 is a selective catalyst for
CLC hydrogenations. Thus, the surface palladium species and
sulfonic acid groups functioned alternately to produce 4 through a
complex but clean one-step process involving hydrogenation, aldol
reaction and dehydration, suppressing the formation of 1-butanol
and 2-ethylhexanol (Scheme 1).
on the resin and stayed active throughout the longterm
continuous-flowing.12
In conclusion, we have developed a novel palladium–acid
bifunctional catalytic system composed of an easily available
catalyst and scCO2. The catalyst exhibits high activity, selectivity
and long lifetime and affords an efficient and selective route to the
industrially important 2-ethylhexanal from crotonaldehyde. The
catalytic system provides the following advantageous features: (i)
the only byproduct is butyraldehyde, which is also industrially
important and can be easily separated by distillation, (ii) a small
excess of hydrogen is sufficient to promote the hydrogenations
owing to the great miscibility of hydrogen and 7 in scCO2, (iii) the
hydrogenations proceed very fast and can be performed at low
temperature (60 uC), (iv) under appropriate conditions the catalyst
exhibits a good long-term behaviour and seems to resist deactiva-
tion caused by the adsorption of reactant, products, CO2 and
byproducts (e.g., water, oligomers) and (v) crotonaldehyde contain-
ing stabilizers can be directly used without further purification due to
the catalyst’s tolerance towards them. The present method thus
may provide a promising alternative for the industrial production
of the two important aldehydes.
Decreasing the total pressure from 16 to 4 MPa by lowering the
CO2 pressure led to a drastic decrease in conversion and selectivity
(entry 4 vs. 5). The low conversion of 7 and the much lower
selectivity of 4 compared to that of 3 (24%) at 4 MPa clearly
demonstrated that the hydrogenation steps were retarded at the
low total pressure due to the increased mass transport limitation of
gaseous hydrogen. Choosing a proper CO2-pressure is thus crucial
for optimizing the performance of this bifunctional catalytic
system.
T.S. thanks Prof. Dr K. Domen and Ms. M. Tomita (The
University of Tokyo) for supporting his activity as a JSPS
Research Fellow. Beamtime granted by HASYLAB and financial
support by the European Community (Contract RII3-CT-2004-
506008) are gratefully acknowledged.
We finally examined the lifetime of the 1% Pd/Amberlyst-15
catalyst for the reaction of 7. As is evident from Fig. 1, this catalyst
exhibited good long-term behaviour under the conditions applied,
continuing to convert 7 into 4 and 2 with quantitative conversion
and y100% selectivity to 4 + 2 for at least 12 h. The selectivities to
4 and 2 did not significantly change throughout time-on-stream.
However, the selectivity to 4 gradually decreased after 7 h
accompanied by an increase in the selectivity to 2. This might be
caused by the decrease in acid sites, namely sulfonic acid groups on
the resin, through the thermal decomposition by the reaction
heat.11 On the other hand, the palladium clusters were firmly fixed
Notes and references
§ The 1% Pd/Amberlyst-15 catalyst was prepared as follows: Into a 50-mL
flask containing a stirring bar were added [Pd(NH3)4]Cl2 (ABCR, 99%;
0.0466 g, 0.190 mmol) and deionized water (20.0 g). After stirring the
mixture for homogenization, Amberlyst1 15 (Fluka, 20–50 mesh, dry
(moisture y5%); 2.00 g) was added, and the resultant heterogeneous
mixture was stirred at 80 uC for 24 h. The solid material was separated by
filtration, washed with deionized water (15 mL) and dried at 100–110 uC
overnight. The as-synthesized catalyst (the reference 1% Pd/C catalyst also)
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Chem. Commun., 2007, 3562–3564 | 3563

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was pre-reduced at 100 uC for 1 h under an H2/N2 flow just before its use
for a reaction.
6 For reviews of heterogeneous catalysis in scCO2, see: (a) A. Baiker,
Chem. Rev., 1999, 99, 453; (b) P. G. Jessop and W. Leitner, Chemical
Synthesis Using Supercritical Fluids, Wiley-VCH, Weinheim, 1999; (c)
J.-D. Grunwaldt, R. Wandeler and A. Baiker, Catal. Rev. Sci. Eng.,
2003, 45, 1; (d) J.-D. Grunwaldt and A. Baiker, Phys. Chem. Chem.
Phys., 2005, 7, 3526.
7 (a) M. G. Hitzler, F. R. Smail, S. K. Ross and M. Poliakoff, Org.
Process Res. Dev., 1998, 2, 137; (b) V. Arunajatesan, B. Subramaniam,
K. W. Hutchenson and F. E. Herkes, Chem. Eng. Sci., 2001, 56, 1363.
8 The reaction conditions were as follows. Total pressure, 16 MPa; reactor
temperature, 60 uC; flow rate of fluid, 1 L min21; flow rate of
cyclohexene, 0.5 mL min21; cyclohexene : H2 = 1 : 1.8. The detailed
results will be published elsewhere.
" SAFETY NOTE: Operators handling high-pressure equipment for
reactions in scCO2 should take proper precautions to minimize the risk of
personal injury. The continuous-flow reactor was composed of a CO2-
compressing unit (NWA, model PM-101), a 6-port valve for introducing
H2 (Rheodyne, model 7000), an HPLC pump for feeding liquid substrates
(Gilson, model 305), a tubular reactor (ETH-workshop, 35 mL volume and
13 mm diameter), an expansion unit (NWA, model PE-103), a sampling
unit and a flowmeter.13 The product sample was collected in a vial
containing a known amount of toluene (internal standard substance). The
mixture was then diluted with ethyl acetate and subjected to analysis by GC
on an instrument equipped with FID (Hewlett Packard, model HP 6890)
that had an HP-5 column (J&W Scientific, 30 m 6 0.32 mm 6 0.25 mm).
9 The reaction of 2 was performed at a total pressure of 16 MPa and a
reactor temperature of 60 uC, employing a 2 : H2 molar ratio of 1 : 2.0,
The column temperature was as follows: 50 uC (10 min) A 20 uC min21
250 uC (5 min). The products were identified by GC-MS and NMR.
A
where the feeding rate of 2 was 0.3 mL min21
.
10 We obtained 7 (¢99.5%, cis : trans = y1 : 20) from Fluka and used it
without further purification. Although the product contained 2,6-di-tert-
butyl-p-cresol and H2O as stabilizers, they had no poisonous effect on
the catalyst.
1 K. Weissermel and H.-J. Arpe, Industrial Organic Chemistry, Wiley-
VCH, Weinheim, 4th edn, 2003.
2 J. J. Spivey and M. R. Gogate, Research Triangle Institute, US EPA
Grant, Pollution Prevention in Industrial Condensation Reactions, 1996.
3 (a) F. King and G. J. Kelly, Catal. Today, 2002, 73, 75; (b) G. J. Kelly,
F. King and M. Kett, Green Chem., 2002, 4, 392; (c) C. A. Hamilton,
S. D. Jackson and G. J. Kelly, Appl. Catal., A, 2004, 263, 63.
4 (a) V. K. Srivastava, S. K. Sharma, R. S. Shukla and R. V. Jasra, Catal.
Commun., 2006, 7, 879; (b) S. K. Sharma, V. K. Srivastava, R. S. Shukla,
P. A. Parikh and R. V. Jasra, New J. Chem., 2007, 31, 277.
5 (a) W. Laufer and W. F. Hoelderich, Chem. Commun., 2002, 1684; (b)
W. Laufer, J. P. M. Niederer and W. F. Hoelderich, Adv. Synth. Catal.,
2002, 344, 1084.
11 The temperature of the catalyst increased to 95–120 uC during the
reaction. This temperature range is below the maximum temperature
recommended for the use of Amberlyst1 15 by Fluka (120 uC).
However, the modification with palladium and, particularly, the high-
pressure condition may promote the thermal decomposition even below
120 uC. For the same discussion, see: R. Amandi, P. Licence, S. K. Ross,
O. Aaltonen and M. Poliakoff, Org. Process Res. Dev., 2005, 9, 451.
12 The XANES spectroscopy of the pre-reduced 1% Pd/Amberlyst-15
(HASYLAB at DESY, Hamburg, Germany) indicated the presence of
metallic Pd(0) clusters on the resin.
13 N. Ku¨nzle, R. Hess, T. Mallat and A. Baiker, J. Catal., 1999, 186, 239.
3564 | Chem. Commun., 2007, 3562–3564
This journal is ß The Royal Society of Chemistry 2007