Chemo-bio catalyzed synthesis of R-1-phenylethyl acetate over bimetallic PdZn catalysts, lipase, and Ru/Al2O3. Part II

Article abstract of DOI:10.1134/S0023158411010095

One-pot synthesis of R-1-phenyethylacetate at 70°C was investigated using three different catalysts simultaneously, namely a bimetallic PdZn/Al ₂O₃ as a hydrogenation catalyst, an immobilized lipase as an acylation catalyst and Ru/Al

Full text of DOI:10.1134/S0023158411010095

ISSN 0023ꢀ1584, Kinetics and Catalysis, 2011, Vol. 52, No. 1, pp. 77–81. © Pleiades Publishing, Ltd., 2011.
ChemoꢀBio Catalyzed Synthesis of Rꢀ1ꢀPhenylethyl Acetate
over Bimetallic PdZn Catalysts, Lipase, and Ru/Al2O3. Part II1
,e
A. Kirilina , P. MäkiꢀArvelaa, K. Kordasb, A.ꢀR. Leinob, A. Shchukarevc, D. Boströmd,
J.ꢀP. Mikkolaa,c, L. M. Kustova, T. O. Salmia, and D. Yu. Murzina
aÅbo Akademi University, Process Chemistry Centre,
Laboratory of Industrial Chemistry and Reaction Engineering, Turku/Åbo, Finland
bUniversity of Oulu, Microelectronics and Materials Physics Laboratories,
Department of Electrical and Information Engineering, Oulu, Finland
cUmeå University, Department of Chemistry, Technical Chemistry, ChemicalꢀBiological Centre, Umeå, Sweden
dUmeå University, Applied Physics and Electronics/Energy Technology and Thermal Process Chemistry,
ChemicalꢀBiological Centre, Umeå, Sweden
eZelinsky Institute of Organic Chemistry, Moscow, 119991 Russia
eꢀmail: dmurzin@abo.fi
Received January 12, 2010
Abstract—Oneꢀpot synthesis of Rꢀ1ꢀphenyethylacetate at 70°C was investigated using three different cataꢀ
lysts simultaneously, namely a bimetallic PdZn/Al2O3 as a hydrogenation catalyst, an immobilized lipase as
an acylation catalyst and Ru/Al2O3 as a racemization catalyst. The most active bimetallic catalyst was
PdZn/Al2O3 calcined at 300°C and reduced at 400°C, whereas the most selective although less active catalyst
was the one being calcined and reduced at 500°C. The highest selectivity to Rꢀ1ꢀphenylethyl acetate over this
catalyst was 32 at 48% conversion. Ru/Al2O3 was confirmed to have a positive effect on the formation of the
desired product, although it was not very active in the racemization during oneꢀpot synthesis.
DOI: 10.1134/S0023158411010095
1
Cascade catalysis is of interest in organic synthesis racemization of the undesired enantiomer resulting in
molar fractions close to 100% of the desired enantiꢀ
omer. The reuse of homogeneous catalysts is challengꢀ
ing and, thus, heterogeneous catalysts compatible with
enzymatic catalysts could be an industrially more
attractive solution. Heterogeneous catalysts can often
be relatively cheap and robust.
both due to high environmental demands aiming at
waste minimization and increasing overall process
efficiency. The Eꢀfactor indicating the amount of
waste per product amount is very high, especially for
fine chemicals [1]. As for process intensification there
are several tools to achieve it via for example enhancꢀ
ing heat and mass transfer by applying ultrasound,
microwaves, etc. An alternative approach to process
intensification is oneꢀpot synthesis, in which the
The model reaction in the current study introduce
illustrates oneꢀpot synthesis of
Rꢀ1ꢀphenylethylaceꢀ
tate ( ꢀ1ꢀPEAc) starting from acetophenone (see
R
underlying idea is to combine two or several different Scheme). In this system, several reactions are comꢀ
bined in oneꢀpot, such as hydrogenation of acetopheꢀ
catalysts and reaction steps in a single apparatus [2].
Already a number of examples is taking advantage of
chemoꢀbio and chemoꢀchemo catalysts in one reactor
unit [3]. There are, however, very few reports that
introduce e.g., a hydrogenation coupled to an enzyꢀ
matic reaction, especially when the hydrogenation
catalyst is a heterogeneous supported metal one.
Although several successful examples could be found
for homogeneous catalyticꢀenzymatic combinations
[4], it should be noted, that homogeneous hydrogenaꢀ
tion catalysts are often very expensive exotic organoꢀ
metallic complexes. In dynamic kinetic resolution,
studied especially by Bäckvall et al. [5], transition
metal catalysts were used as additional catalysts for
none, acylation of the formed
R
S
ꢀ1ꢀphenylethanol
ꢀ1ꢀphenylethanol
(
(
Rꢀ1ꢀPE) and racemization of
S
ꢀ1ꢀPE). The latter reaction allows dynamic kinetic
ꢀenantiomer is racemized during
the reaction. This facilitates formation of ꢀ1ꢀPEAc
in higher than 50% yields, since ꢀenantiomer is
transformed to ꢀ1ꢀenantiomer and can, conseꢀ
quently, be acylated in the following reaction sequel.
Oneꢀpot synthesis of ꢀ1ꢀPEAc has been demonꢀ
resolution, i.e., the
S
R
S
R
R
strated in the previous publications [6, 7], when only a
monometallic supported Pd catalyst was applied for
acetophenone hydrogenation followed by lipase cataꢀ
lyzed acylation of the
desired product—
about 22%, at a conversion level of 46% [6]. In addiꢀ
R
ꢀ1ꢀPE. The highest yield of the
Rꢀ1ꢀphenylethylacetate—was
1
The article is published in the original.
77

78
KIRILIN et al.
Racemization catalyst
OH
OAc
OH
O
H2
EtOAc, Lipase
–EtOH
+
Pd/Al2O3
AP
R,S–PE
R–PEAc
S–PE
H2, Pd/Al2O3
–H2O
–H2O
–AcOH
H2, Pd/Al2O3
–H2O
or via styrene formation
H2, Pd/Al2O3
–EtOH
STY
EB
Scheme. Oneꢀpot synthesis of Rꢀ1ꢀphenylethylacetate.
tion to hydrogenation and acylation reactions, a sideꢀ
reaction leading to the formation of ethylbenzene was
quite prominent [6]. Ethylbenzene (EB) can be
formed over Pd metal via debenzylation of the desired
ester. One possibility to decreased the EB formation
would be to use a bimetallic PdZn catalyst for aceꢀ
tophenone hydrogenation. A similar catalyst was
reported in [8] giving less ethylbenzene than a monoꢀ
metallic Pd/C catalyst.
EXPERIMENTAL
Kinetic experiments were performed in a standard
laboratory scale glass reactor. Acetophenone was used
as the reactant and its initial concentration was
0.02 mol/l in toluene. The liquid phase volume was
125 ml. Ethyl acetate (0.06 mol/l) was used as an acyl
donor in toluene solvent. Acetophenone hydrogenaꢀ
tion was performed at 70°C over PdZn/Al2O3 as the
hydrogenation catalyst, an immobilized lipase
(Novozym 435) as the acylation catalyst and Ru/Al2O3
as the racemization catalyst. After prereduction, cataꢀ
lysts were kept under toluene in order to avoid oxidaꢀ
tion. In a typical experiment, hydrogenation was perꢀ
formed under an atmospheric flow of hydrogen
(300 ml/min) and 312 mg of the PdZn/Al2O3 together
with 62.5 mg lipase and 100 mg Ru/Al2O3 catalysts
were mixed. The experiments were performed under
kinetic regime using the stirring rate of 500 rpm. Furꢀ
thermore, the particle size fraction of all supported
Racemization of the unreacting enantiomer is typꢀ
ically performed over a Ru/Al2O3 catalyst, in which
Ru exists in the oxide form [9, 10].
The aim in the current work was to study the cataꢀ
lytic activity and selectivity of a bimetallic
PdZn/Al2O3 catalyst, together with a lipase as an acyꢀ
lation catalyst and with Ru/Al2O3 as a racemization
catalyst for Sꢀ1ꢀPE. The synthesis and characterizaꢀ
tion of a bimetallic PdZn/Al2O3 and Ru/Al2O3 were
reported in Part I [10]. The industrially important
metal catalysts was below 63
diffusion.
µ
m to suppress internal
product is
via hydrolyzing
R
ꢀ1ꢀPE, which is usually easily produced
Rꢀ1ꢀPEAc in sodium hydroxide [11].
Oneꢀpot synthesis of Rꢀ1ꢀPEAc starting from acetophenone hydrogenation*
Selectivity to
R
ꢀPEAc, %
Selectivity to EB, %
Calcination Reduction
Entry temperature, temperaꢀ
Conversion
after 360
min, %
Initial rate,
mmol min–1 gP–d1
at 50% conꢀ at 90% conꢀ at 50% conꢀ at 90% conꢀ
versionat
°C
ture, °C
version
versionat
version
1
2
3
300
500
500
400
400
500
2.7
1.5
1.6
90
75
48
25
25
32
33
–
0
4
3
6
–
–
–
* Catalysts: (2 wt % Pd + 5 wt % Zn)/Al O (315 mg), 4 wt % Ru/Al O (100 mg), lipase (62.5 mg). Conditions: initial concentration
2
3
2 3
of acetophenone 0.02 mol/l, 70°C, solvent toluene, 3 equivalents of ethyl acetate as an acyl donor.
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CHEMOꢀBIO CATALYZED SYNTHESIS OF
Rꢀ1ꢀPHENYLETHYL ACETATE... II
79
Concentration of acetophenone, mol/l
Concentration of
0.006
Rꢀ1ꢀPE, mol/l
(c)
0.020
(a)
1
0.005
0.004
0.003
0.002
0.001
0
0.015
0.010
3
2
3
0.005
2
1
0
0
100 200 300 400 500 600
Time, min
0
20
40
60
80 100
Conversion, %
Concentration of
0.0025
R
ꢀ1ꢀPE, mol/l
Concentration of EB, mol/l
0.010
(b)
(d)
0.0020
1
0.008
0.006
0.004
0.002
0
2
2
0.0015
0.0010
0.0005
0
3
1
0
100 200 300 400 500 600
Time, min
0
20
40
60
80 100
Conversion, %
Fig. 1. Kinetics of acetophenone hydrogenation (a) and
R
ꢀ1ꢀPE formation (b), also formation of
R
ꢀ1ꢀPEAc (c) and ethylacetate
(d) as functions of conversion in oneꢀpot synthesis at 70°C on the samples:
1—PdZnꢀ300ꢀ400,
2—PdZnꢀ500ꢀ400, —PdZnꢀ
3
500ꢀ500. Initial concentrations of acetophenone and ethylacetate 0.02 and 0.06 mol/l, respectively. The amounts of catalysts:
PdZn/Al O —312 mg, lipase—62.5 mg, 4 wt % Ru/Al O —100 mg.
2
3
2 3
RESULTS AND DISCUSSION
use a catalyst which has been calcined at 300°C. Furꢀ
thermore, the most active catalyst exhibited the highꢀ
est surface concentrations of Pd and Zn [10], conꢀ
firmed by XPS results.
The effects of catalyst calcination and reduction
temperatures were evaluated using (2 wt % Pd +
5 wt % Zn)/Al2O3 as the hydrogenation catalyst, lipase
as the acylation catalyst and 4 wt % Ru/Al2O3 as the
racemization catalyst. The reactions were performed
at 70°C, in toluene (0.02 and 0.06 mol/l of acetopheꢀ
none and ethyl acetate, respectively).
Large differences were observed in the acetopheꢀ
none conversion after 360 min for the three different
PdZn/Al2O3 catalysts. Consequently, the conversion
levels were decreased in row PdZnꢀ300ꢀ400 PdZnꢀ
ӷ
500ꢀ400 PdZnꢀ500ꢀ500 indicating that high cataꢀ
The highest initial hydrogenation rate was achieved
ӷ
over the catalyst calcined at 300°C and reduced at lyst reduction temperatures (500°C) should be
400°C (table), whereas lower initial activities were avoided (table, Fig. 1a), as it easily leads to slight sinꢀ
observed for the catalysts calcined at 500°C and tering of metal particles as confirmed by TEM [10].
reduced thereafter either at 400 or at 500°C. These The more low reaction rates were observed after
results can be explained by the fact that large Pd partiꢀ 30 min for the catalyst both calcined and reduced at
cles were also detected in the cases, when the catalysts 500°C (only 48% conversion of acetophenone after
were calcined at 500°C [10]. Thus, it is preferable to 360 min).
KINETICS AND CATALYSIS Vol. 52
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80
KIRILIN et al.
The formation of the desired ester product—Rꢀ1ꢀ
Concentration of
0.007
Rꢀ1ꢀPEAc, mol/l
PEAc—was compared at the same conversion levels
(Fig. 1c). It was seen that the highest concentrations of
it were achieved over the catalyst calcined at 500°C
and reduced at 500°C. The challenge associated with
this catalyst was, however, its low activity. The best
performance was observed over the catalyst PdZnꢀ
2
0.006
0.005
0.004
0.003
0.002
0.001
0
1
300ꢀ400, giving the yield of
thermore, the enantiomeric excess of
R
ꢀ1ꢀPEAc of 30%. Furꢀ
Rꢀ1ꢀPEAc was
100%. For the catalyst PdZnꢀ500ꢀ400, the consecuꢀ
tive debenzylation reaction occurred very prominently
after 80% conversion (Fig. 1c). Debenzylation is
known to be catalyzed especially by Pd. XPS analysis
in line showed that the fraction of the metallic Pd(0)
for the most selective catalyst (PdZnꢀ300ꢀ400) was the
lowest, namely 40% [10]. On the other hand, the least
selective catalyst (PdZnꢀ500ꢀ400 active due to presꢀ
ence of not too large metal particles) displayed a high
fraction of Pd(0) (46%) [10], a value larger than that
for PdZnꢀ300ꢀ400. Furthermore, for the catalyst
exhibiting low activity, namely PdZnꢀ500ꢀ500, the
high fraction of metallic Pd was not very effective
because of large metal particles size.
−
0.001
0
20
40
60
80
100
Conversion, %
Fig. 2. Formation of
none conversion in the absence (
of Ru/Al O catalyst. Conditions of reaction: temperature
R
ꢀ1ꢀPEAc as a function of acetopheꢀ
1) and in the presence (
2)
2
3
70°C, solvent toluene, initial concentrations of acetopheꢀ
none and ethylacetate 0.02 and 0.06 mol/l, respectively.
The amounts of the catalysts: PdZnꢀ300ꢀ400—312 mg,
The behavior of the racemization catalyst—
Ru/Al2O3—was investigated by performing two comꢀ
lipase—62.5 mg, 4 wt % Ru/Al O —100 mg.
2
3
parative experiments in the oneꢀpot synthesis of Rꢀ1ꢀ
PEAc over the most active hydrogenation catalyst
PdZnꢀ300ꢀ400 and lipase both in the presence and in
the absence of the racemization catalyst. The hydrogeꢀ
nation rates were identical in both cases as expected,
since Ru is in higher oxidation state known to be not
The product distribution obtained over different
PdZn/Al2O3 catalysts varied very much depending on
the pretreatment conditions (Fig. 1, table). The highꢀ
est concentration of the intermediate product—Rꢀ1ꢀ
phenylethanol—was achieved for the most active catꢀ active in the hydrogenation.
alyst, i.e., the one calcined at 300°C and reduced at
400°C. Furthermore, the ꢀ1ꢀPE yield decreased in
The presence of the racemization catalyst proꢀ
moted the formation of ꢀ1ꢀPEAc. At 90% converꢀ
sion level, the concentration of the product, ꢀ1ꢀ
PEAc, was 0.0058 mol/l, whereas only 0.0047 mol/l
was achieved in the absence of the Ru/Al2O3 (Fig. 2).
R
R
line with the trend observed in the catalyst activities
and conversions. Consequently, the catalyst calcined
at 300°C and reduced at 400°C exhibited the highest
R
Concentration of Sꢀ1ꢀPE as a function of time, was,
activity towards
Rꢀ1ꢀPE. For all three catalysts, maxꢀ
however, monotonously increasing with increasing
conversion as stated above and no clear racemization
or hydrogenolysis of it could be observed. In any case
more Rꢀ1ꢀPEAc was formed in the presence of racemꢀ
ization catalyst.
ima in the ꢀ1ꢀPE concentration as a function of time
were observed (Fig. 1b).
R
In contrast to the kinetic curves observed for Rꢀ1ꢀ
PE, no maxima were observed for Sꢀ1ꢀPE over differꢀ
ent PdZn catalysts as a function of time. The yield of
Thus, oneꢀpot synthesis of Rꢀ1ꢀphenylethylacetate
S
ꢀ1ꢀPE increased with increasing time indicating that
two ꢀ1ꢀPE transformation reactions, namely racemꢀ
ization and hydrogenolysis, were not very prominent
since the rate of ꢀ1ꢀPE formation was always higher
than its consumption rate in the consecutive reactions.
Racemization of ꢀ1ꢀPE has been confirmed in a sepꢀ
arate experiment in toluene, at 70°C, over Ru/Al2O3.
The contribution from the racemization of ꢀ1ꢀPE
was investigated over three different heterogeneous
catalysts being present in the reactor simultaneously,
namely a bimetallic PdZn/Al2O3 for hydrogenation,
an immobilized lipase for acylation and Ru/Al2O3 for
S
S
racemization of the undesired
Sꢀ1ꢀphenylethanol.
S
The experiments were performed at 70°C, in toluene
as the solvent, using 3 equivalents of ethylacetate as the
acyl donor.
S
cannot be precisely quantified, but the effect is not
very significant. It has been stated in [12] that the raceꢀ
The effect of calcinations and reduction temperaꢀ
ture of PdZn/Al2O3 catalysts on oneꢀpot synthesis of
mization of
esters. In the current case ethylacetate used as an acyl
donor, moreover, the desired product— ꢀ1ꢀPEAc—
Sꢀ1ꢀPE was inhibited by the presence of
R
ꢀ1ꢀPEAc was investigated too. The most active cataꢀ
lyst was one calcined at 300°C and reduced at 400°C
due to slightly smaller metal particles compared to the
two other catalysts. This catalyst exhibited the highest
surface concentration of Pd and Zn according to XPS
R
is also an ester. Thus, this could lead to deactivation of
Ru/Al2O3 catalyst.
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CHEMOꢀBIO CATALYZED SYNTHESIS OF
Rꢀ1ꢀPHENYLETHYL ACETATE... II
81
analysis. The highest yield of the desired product—Rꢀ
REFERENCES
1ꢀPEAc—was 30 at 90% conversion of acetophenone
over the PdZn/Al2O3 catalyst, calcined at 300°C and
reduced at 400°C. The enantiomeric excess of Rꢀ1ꢀ
PEAc was 100%.
1. Sheldon, R.A., Arens, I., and Hanefeld, U., Green
Chemistry and Catalysis, Weinheim: WileyꢀVCH, 2007.
2. Bruggink, A., Schoevaart, R., and Kieboom, T., Org.
Proc. Res. Dev., 2003, vol. 7, p. 622.
The yield of
active catalyst calcined at 300°C and reduced at
400°C. After longer reaction time, ꢀ1ꢀPE reacted to
ꢀ1ꢀPEAc and partially to ethylbenzene via hydroꢀ
genolysis. The extent of racemization of ꢀ1ꢀPE was
Rꢀ1ꢀPE was highest over the most
3. Murzin, D.Yu. and Leino, R., Chem. Eng. Res. Des.
2008, vol. 86, p. 1002.
,
R
4. Jung, H.M., Koh, J.H., and Kim, M.ꢀJ., Park, J. Org.
Lett., 2000, vol. 2, p. 2487.
R
S
5. Persson, B.A., Huerta, F.F., and Bäckvall, J., J. Org.
Chem., 1999, vol. 64, p. 5237.
quite minor due to the fact that alcohols and esters
inhibit the racemization reaction. When comparative
6. MäkiꢀArvela, P., Sahin, S., Kumar, N., Heikkilä, T.,
Lehto, V.ꢀP., Salmi, T., and Murzin, D.Yu., J. Mol.
Catal. A: Chem., 2008, vol. 285, p. 132.
experiments in oneꢀpot synthesis of Rꢀ1ꢀPEAc, both
in the presence and in the absence of Ru/Al2O3, were
performed, it was found that 19% higher concentraꢀ
tion of
R
ꢀ1ꢀphenyethylacetate was achieved in the
7. MäkiꢀArvela, P., Sahin, S., Kumar, N., Heikkilä, T.,
Lehto, V.ꢀP., Salmi, T., and Murzin, D.Yu., Appl.
Catal., A, 2008, vol. 350, p. 24.
presence of Ru/Al2O3. This result indicated that
Ru/Al2O3 exhibited a positive overall effect on the
oneꢀpot synthesis of Rꢀ1ꢀPE.
8. Lenarda, M., Moretti, E., Storaro, L., Patrono, P., Pinꢀ
zari, F., RodriguezꢀCastellón, E., JimenézꢀLópez, A.,
Busca, G., Finocchio, E., Montanari, T., and Frattini, R.,
Appl. Catal., A, 2006, vol. 312, p. 220.
ACKNOWLEDGMENTS
This work is part of the activities at the Åbo Akaꢀ
demi Process Chemistry Centre (ÅAꢀPCC) within the
Finnish Centre of Excellence Programme (2000–
2011) appointed by the Academy of Finland. The
authors are grateful to the Academy of Finland for the
financial support under the grants 120853, 124357,
and 128626. This work is also associated with the
activities of Umeå University ChemicalꢀBiological
Centre whereupon financial support from Umeå Uniꢀ
versity, Kempe foundation and Markus Wallenberg
foundation are acknowledged.
9. Yamaguchi, K., Koike, T., Kim, J.W., Ogasawara, Y.,
and Mizuno, N., Chem. Eur. J., 2008, vol. 14, p. 11 480.
10. Kirilin, A., MäkiꢀArvela, P., Kordas, K., Leino, A.ꢀR.,
Shchukarev, A., Boström, D., Mikkola, J.ꢀP., Kusꢀ
tov, L.M., Salmi, T.O., and Murzin, D.Yu., Kinet.
Catal., 2011, vol. 52, p. 72.
11. Yu, H., Wang, B., Tang, X., and Liu, L., Chinese Patent
101503727, 2008.
12. Wuyts, S., de Vos, D.E., Verpoort, F., Depla, D., de
Gryse, R., and Jacobs, P., J. Catal., 2003, vol. 219,
p. 417.
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2011