Sol-gel immobilized catalyst systems for tandem transformations with trans-stilbene as an intermediate

Article abstract of DOI:10.1016/j.catcom.2014.04.016

Tandem catalytic systems containing one or two sol-gel immobilized catalysts were successfully applied in the synthesis of trans-stilbene oxide and 1,2-diphenylethane. The catalysts were prepared from palladium and/or manganese precursors in the presence of orthosilicates using a sol-gel method and could be reused several times successfully.

Full text of DOI:10.1016/j.catcom.2014.04.016

Catalysis Communications 53 (2014) 1–4
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Sol-gel immobilized catalyst systems for tandem transformations with
trans-stilbene as an intermediate
b
b
c
a
I. Volovych a, M. Schwarze a, , Z. Nairoukh , J. Blum , M. Fanun , R. Schomäcker
⁎
a
Institute of Chemistry, Berlin Institute of Technology, Straße des 17. Juni 124, D-10623 Berlin, Germany
Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
Center for Colloid and Surface Research, Al-Quds University, East Jerusalem 51000, Palestinian Authority
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Tandem catalytic systems containing one or two sol-gel immobilized catalysts were successfully applied in the
synthesis of trans-stilbene oxide and 1,2-diphenylethane. The catalysts were prepared from palladium and/or
manganese precursors in the presence of orthosilicates using a sol-gel method and could be reused several
times successfully.
Received 22 February 2014
Received in revised form 16 April 2014
Accepted 18 April 2014
Available online 26 April 201
© 2014 Elsevier B.V. All rights reserved.
Keywords:
Palladium acetate
Sol-gel immobilized catalyst
Tandem reaction
Trans-stilbene
1. Introduction
were replaced by more environmentally friendly media, namely aqueous
microemulsions. Supported palladium, manganese and palladium–
One of the recent trends in modern chemical process research is the
development of greener processes. Paul Anastas formulated some sim-
ple rules about achieving sustainability in the production of chemicals,
e.g. avoiding waste, working with high atom efficiency, usage of cata-
lysts and renewable feed stocks. In this case more environmentally
friendly processes can be realized by reusing solvents, catalysts and
organic components after each reaction which reduces the costs and
the environmental impact of the process by applying green solvents
(e.g., water) in the synthesis of the desired products.
manganese catalysts synthesized by using a sol-gel method were used
in the process to improve catalyst recycling. The general mechanism
of the sol-gel process is known, but the influence of immobilization on
different metals in the silica matrix was studied only for selected
examples [4–7]. In this case, we tried to determine the parameters that
influence the activity and stability of sol-gel-immobilized catalysts and
compare their performance.
In the course of our work, we developed and tested green reaction
routes with trans-stilbene as an intermediate (Scheme 1), which is an im-
portant component in pharmaceuticals and fine chemicals, e.g. Herbicide
Prosulfuron™, antiasthma agent Singulair™, analgesic drug Naproxen
[1], anticancer agent Paclitaxel (Taxol®) [2], stilbenoid resveratrol
with anti-tumor properties and optically active distyrylbenzene or
styrylbiphenyl [3], which can be used as fluorescent dopants in organic
light emitting diodes and lasers.
Two different tandem reactions were selected: the synthesis of
trans-stilbene using Heck coupling followed by hydrogenation to
1,2-diphenylethane and epoxidation to trans-stilbene oxide. Following
the concepts of green chemistry, the conventional organic solvents
2. Experimental
2.1. Instrumentation
All reagents were commercially available and used without further
purification. The conversion (X) and yield (Y) were obtained using
high performance liquid chromatography (HPLC) on an Agilent instru-
ment 1200 series from Agilent Technologies Waldbronn/Germany
with 250 × 4 mm chromatographic column Multospher 120 RP18-5μ
from Ziemer Chromatographie Langerwehe/Germany. N2-BET specific
surface areas, pore volumes and pore size distributions were obtained
using a Micromeritics Gemini 1325 instrument from Micromeritics
GmbH Aachen/Germany. The amounts of palladium, manganese and
phosphorus leached from the catalysts into the reaction mixtures
were analyzed using a Varian 715-ES Optical Emission Spectrometer
from Varian Inc. Middelburg/Netherlands.
⁎
Corresponding author. Tel.: +49 3031424097.
E-mail address: ms@chem.tu-berlin.de (M. Schwarze).
http://dx.doi.org/10.1016/j.catcom.2014.04.016
1566-7367/© 2014 Elsevier B.V. All rights reserved.

2
I. Volovych et al. / Catalysis Communications 53 (2014) 1–4
Scheme 1. Tandem reactions.
2.2. Catalyst synthesis
2.3. Reaction procedure
For the preparation of the catalysts on a hydrophobically modified
surface, a solution of 2.1 mL of trimethoxy(octyl)silane (9.877 mmol)
or 1.612 mL triethoxyphenylsilane (6.680 mmol) in 0.4 mL water and
4.25 mL methanol or ethanol was hydrolized for 24 h. Then, 3.6 mL of
tetramethyl orthosilicate (22.961 mmol) in 2.4 mL of methanol and
2 mL of water was stirred for 20 min. The solutions were combined
and stirred for another 30 min. Then, 30 mg of palladium(II) acetate,
35 mg of palladium(II) bromide, 33 mg of manganese(II) acetylacetonate
(0.134 mmol) or a mixture of palladium(II) bromide and manganese(II)
acetylacetonate catalyst precursor with/without 30.420 mg of XantPhos
(0.134 mmol) or 1.24 g of 30% TPPTS/H2O (0.640 mmol) ligand were
dissolved in 4 mL of dichloromethane, stirred for 20 min (12 h with
ligand) and combined with the silane solution and stirred until gelation
occurred. The hydrophilically modified immobilized palladium (II) ace-
tate catalyst was prepared without the addition of hydrophobic silane
to the hydrolized tetramethyl orthosilicate. The catalyst was dried for
4–8 h at 80 °C followed by drying for 8–12 h at 80 °C and 103 Pa, washing
with dichloromethane and drying at 80 °C and 103 Pa for 8–10 h. Finally,
1.25 wt.% Pd(OAc)2 with/without ligand on silica support, 1.47 wt.%
Mn(Acac)2 or 1.06 wt.% Pd(OAc)2/1.20 wt.% Mn(Acac)2 with/without
ligand on PhSiO2 were obtained.
The Heck coupling, epoxidation and tandem reactions were per-
formed in a double-walled, stirred glass reactor with a reflux condenser.
The hydrogenation reactions were performed in 100 mL of methanol or
an aqueous microemulsion at an 800 rpm stirring rate and 1.1 × 105 Pa
H2 in a stirred tank reactor. The cumulative hydrogen consumption and
the pressure during the reaction were measured using a Bronkhorst
flow meter and pressure controller (Bronkhorst Mättig GmbH, Kamen/
Germany) and recorded on a PC. From these results the substrate con-
centration csubstrate and the conversion X were calculated. All reactions
were conducted in one phase aqueous microemulsions, consisting
of 1.510 g CTAB as the surfactant (5.235 mmol, 3.3 wt.%), 3.020 g
1-propanol (50.250 mmol, 6.6 wt.%) as the cosurfactant, 40.855 g of
H2O (2269.722 mmol, 89.3 wt.%) and reactants (2.84 mmol, 0.8 wt.%).
For Heck coupling, 1.34 mmol alkene and 1.50 mmol aryl halide were
dissolved in a 46 mL microemulsion with 0.276 g K2CO3 (2.00 mmol)
Table 2
Trans-stilbene synthesis via Heck coupling.a
Table 1
Optimization of reaction conditions in the synthesis of trans-stilbene.a
Entry
W
X
Y
Time (min)
Yield (%)
Entry
Catalyst
Support
Surfactant
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
H
H
H
H
Cl
Cl
H
H
Cl
Br
I
Br
Br
I
H
H
H
I
H
H
327
555
480
398
371
415
419
448
62
100
94
1
2
3
4
5
6
7
8
9
Pd(OAc)2
PdBr2
Pd(OAc)2/Xantphos
Pd(OAc)2/TPPTS
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PhSiO2
PhSiO2
PhSiO2
PhSiO2
SiO2
OcSiO2
PhSiO2
PhSiO2
PhSiO2
PhSiO2
CTAB
CTAB
CTAB
CTAB
CTAB
CTAB
TTAB
DTAB
SDS
396
386
352
416
394
300
405
371
380
388
96
66
74
73
60
81
54
58
96
92
89b
50c
92c
0d
Cl
Br
styrene
styrene
20d
a
1.34 mmol styrene, 1.5 mmol haloarene, 2 mmol K2CO3, 1.25 wt.% Pd(OAc)2@PhSiO2,
46 mL microemulsion, 80 °C.
10
Pd(OAc)2
TX-100
b
4-trans-bromostilbene.
4-trans-chlorostilbene.
Tandem Heck–Heck domino reaction.
a
c
1.34 mmol styrene, 1.5 mmol bromobenzene, 2 mmol K2CO3, 1.25 wt.% Pd(OAc)2@
silica support, 46 mL microemulsion, 80 °C.
d

I. Volovych et al. / Catalysis Communications 53 (2014) 1–4
3
Table 3
Synthesis of 1,2-diphenylethane via the tandem Heck-hydrogenation.
Entry
Time [min]
YieldHeck (%)a
Time (min)
YieldHydrogenation (%)b
1
2
3
4
500
500
100
100
283
100
97c
268
33(25f)
378
100d,e
85d
a
2.68 mmol styrene, 3 mmol iodobenzene, 4 mmol K2CO3, 1.25 wt.% Pd(OAc)2@PhSiO2 (0.1334 mmol Pd(OAc)2), 100 mL microemulsion (3 g CTAB/6.04 g propanol/81.7 g H2O),
80 °C.
b
c
d
e
f
1.1 × 105 Pa H2, 800 rpm, 60 °C.
1200 rpm.
Commercial trans-stilbene at 40 °C.
Methanol.
Homogeneous not supported Pd(OAc)2.
as the base. For epoxidation, 0.2415 g trans-stilbene (1.34 mmol) and
0.34 g H2O2 (10 mmol) or 0.573 g NaIO4 (2.68 mmol) as the oxidizing
agent were added to the 46 mL microemulsion. The hydrogenation
reaction was carried out with 0.483 g of trans-stilbene (2.368 mmol).
reactions [8,9]. In addition, the hydrophobically modified supports form
more branched and stable pore structures which allow for better metal
incorporation in the pores of the catalyst.
The synthesis of trans-stilbene and derivatives was conducted under
optimized conditions at 80 °C with Pd(OAc)2@PhSiO2 as the catalyst.
The reactivity and solubility of haloarenes decrease when using less
active substituents with the expected ranking of Cl b Br ≈ para-I/Br b I
(Table 2, Entry 1–4). The synthesis of 4-trans-chlorostilbene (Table 2,
Entry 5–6) or 4-trans-bromostilbene (Table 1, Entry 4) from 4-
chlorostyrene and iodobenzene or styrene and 1-bromo-4-iodobenzene
can also be applied in the further synthesis of distyrylbenzene (Table 2,
Entry 7–8). The synthesis of this very hydrophobic substrate is quite
difficult because of the low substrate solubility and reactivity.
3. Results and discussion
3.1. Heck coupling
First, the Heck reaction was investigated in detail as the starting point
for the tandem synthesis. The coupling of styrene and bromobenzene
to trans-stilbene as the main product was catalyzed by a sol-gel-
immobilized palladium (II) catalyst in one phase microemulsions
containing primarily water, propanol and ionic (Table 1, Entry 6–9)
or nonionic (Table 1, Entry 10) surfactants. The sol-gel-immobilized cata-
lysts without ligand addition had large specific surface areas of A = 250–
300 m2/g. Average pore volumes of Vpore = 0.176 cm3/g and pore diam-
eters of dpore ≤ 2.45 nm were found. The best results for the trans-stilbene
synthesis were obtained with Pd(OAc)2 immobilized on hydrophobically
modified silica (Table 1, Entry 1) with only 0.0122% of palladium acetate
leaching into the reaction mixture. PdBr2, with only 0.05% leaching, repre-
sents an alternative to palladium acetate. We realized that the addition of
the air sensitive Xantphos or TPPTS ligands (Table 1, Entry 3 and 4) was
not necessary because higher rates and yields were already obtained
without their addition. In comparison to the hydrophilic silica (Table 1,
Entry 5), the reaction rates were higher when using the hydrophobic
support materials (Table 1, Entry 1 and 6) because of hydrophobic inter-
actions between the surface of the support material and the aromatic sub-
strates as already shown in earlier publications for other sol-gel catalyzed
3.2. Tandem Heck-hydrogenation
Aryl-substituted 1,2-diphenylethanes are intermediates for the
synthesis of potential anti cancer agents [10], which are inhibitors for
retinoic acid metabolizing enzyme. The Heck reaction of iodobenzene
and styrene to trans-stilbene in an aqueous microemulsion was success-
fully combined with the hydrogenation to 1,2-diphenylethane in a
Heck-hydrogenation tandem reaction with only one Pd(OAc)2@PhSiO2
catalyst (Auto-tandem catalysis). The results obtained for the hydroge-
nation of the not isolated intermediate product trans-stilbene (Table 3,
Entry 1–2) were comparable with the results obtained for the hydroge-
nation of commercially available trans-stilbene in methanol and
microemulsions (Table 3, Entry 3–4). The catalyst was very stable and
a negligible amount of palladium leached from the support (b0.004%
Pd(OAc)2).
Table 4
Synthesis of trans-stilbene oxide via tandem Heck-epoxidation.
Entry
Catalyst precursor
Time (min)
1430
YieldHeck (%)a
100
Time (min)b
415
YieldEpoxidation 1a (%)b
2 (22% 1c/25%1c)
Time (min)c
YieldEpoxidation 1a (%)c
1
2
3
4
5
Pd(OAc)2
Mn(Acac)2
PdBr2 − Mn(Acac)2
PdBr2 − Mn(Acac)2 − Xantphos
Pd(OAc)2 + Mn(Acac)2
417
365
55 (20% 1b)
24 (44% 1d)
53 (6% 1d)
33 (31% 1b)
1392
1240
1393
100
100
100
423
259
424
2 (10%1c/15%1d)
(30% 1d)
30% (2%1b/14% 1d)
404
d
a
1.34 mmol styrene, 1.5 mmol iodobenzene, 2 mmol K2CO3, 1.25 wt.% Pd(OAc)2@PhSiO2, 46 mL microemulsion, 80 °C.
2.68 mmol NaIO4, 80 °C.
Commercial trans-stilbene.
b
c
d
Removal of Pd(OAc)2 and addition of Mn(Acac)2@PhSiO2 catalyst after the Heck coupling.

4
I. Volovych et al. / Catalysis Communications 53 (2014) 1–4
activity of the catalyst in the tandem reaction compared to the bench-
mark experiments can be explained by the high catalyst leaching ob-
served during the reaction and also by the insufficient purity of the
intermediate trans-stilbene product that emphasizes the importance
of the performance of the first step of a tandem process. While the
above described hydrogenation is insensitive to minor components as-
sociated with the trans-stilbene the epoxidation is strongly disturbed
by such components. Further research is needed to reduce these com-
ponents without a complete isolation of the intermediate product.
4. Conclusion
In summary, we have synthesized hydrophobically and
hydrophilically modified palladium, manganese and palladium–manga-
nese catalysts and applied them in tandem reactions with trans-stilbene
as the intermediate. The influence of additives, e.g. oxidizing agents,
hydrophobicities of the supports, solvents, interactions between the
substrate and immobilized catalysts was studied. The catalyst stability
and recycling depends not only on the metal type, but also on the addi-
tives and reaction types. Pd(OAc)2@PhSiO2 could be successfully
recycled 6 times without leaching and catalyst deactivation after Heck
coupling of iodobenzene and styrene (Fig. 1a). The reuse of the palladi-
um and manganese catalysts after the epoxidations was much more dif-
ficult, because of the strong catalyst leaching into the reaction mixture
caused by the addition of strong oxidizing agents to the reaction
mixture (Fig. 1b). Generally, heterogeneous manganese catalysts are
less stable than palladium catalysts, but more appropriative for epoxida-
tions. The addition of palladium to the manganese catalyst causes a
synergistic effect that increases the reactivity of the catalyst.
The main challenge in performing tandem reactions is the presence
of impurities in the intermediate products, which interfere with the
catalyst of the second reaction and decrease the selectivity of the overall
reaction.
Fig. 1. Catalyst recycling (a) Heck coupling (b) epoxidation (46 mL microemulsion, 80 °C,
Heck: 1.34 mmol styrene, 1.5 mmol iodobenzene, 2 mmol K2CO3, Pd(OAc)2@PhSiO2,
epoxidation: 1.34 mmol styrene or trans-stilbene, 10 mmol H2O2 or 2.68 mmol
NaIO4, Mn(Acac)2@PhSiO2).
Acknowledgments
We gratefully acknowledge the financial support for this study from
the Deutsche Forschungsgemeinschaft (DFG) through grant SCHO687/
8-2.
3.3. Tandem Heck-epoxidation
Trans-stilbene oxide inhibits drug-metabolizing enzymes, e.g. epox-
ide hydratase [11], and can also be used in the synthesis of different
products such as antihypertensive drugs or Metoprolol [12], through
ring opening reactions with nitrogen, oxygen or sulfur containing
nucleophiles. There are several optional synthesis routes that use
tandem Heck-epoxidation: Pd(OAc)2@PhSiO2 (auto tandem catalysis),
PdBr2 − Mn(Acac)2@PhSiO2 with/without stabilizing Xantphos ligand
(orthogonal catalysis) or Pd(OAc)H2 eck and Mn(Acac)E2poxidation (one pot
synthesis). The main challenge in performing the epoxidation reaction
is a large fraction of undesired by-products because of the over oxida-
tion of the main product.
The yields of the desired product (trans-stilbene oxide) obtained via
the tandem reaction were in all cases rather low (Y = 2–30%) and
mainly benzaldehyde and styrene oxide as byproducts were obtained
(Table 4). In comparison to these results, a 50% yield of trans-stilbene
oxide was obtained from commercial trans-stilbene via epoxidation
with palladium and palladium–manganese catalysts. The decreased
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