Mechanistic investigations of the reaction network in chemo-bio catalyzed synthesis of R-1-phenylethyl acetate

Article abstract of DOI:10.1134/S0023158410060054

The kinetics and reaction network of the one-pot synthesis of R-1-phenylethyl acetate was inves-tigated at 70°C in toluene over a combination of three different catalysts: PdZn/Al₂O₃ as a catalyst for acetophenone hydrogenation, lipase as an enzymatic catalyst for R-1-phenylethanol acylation with ethyl acetate and Ru/Al₂O ₃ as a racemization catalyst for S-1-phenylethanol. In addition to the desired reactions, other reactions, namely hydrogenolysis and dehydration of (R, S)-1-phenylethanol and debenzylation of (R, S)-1- phenylethyl acetate also occurred. The kinetic results revealed that ethylbenzene formation was enhanced with higher amounts of PdZn/Al₂O₃, whereas lipase did not catalyze ethylbenzene formation. Furthermore, ethylbenzene was formed in the hydrogenolysis of (R, S)-phenylethanol and in the debenzylation of (R, S)- 1-phenyl-ethylacetate over Pd/Al₂O₃ catalyst. The presence of Ru/Al₂O₃ catalyst, in which Ru was in the oxi- dation state of ³⁺, enhanced the formation of R-1-phenylethyl acetate, although no clear racemization of S-1-phenylethanol during the one-pot synthesis of R-1-phenylethyl acetate was observed. Dynamic kinetic resolution of (R, S)-1-phenylethanol in toluene, was, however, demonstrated over Ru/Al ₂O₃ and lipase. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S0023158410060054

ISSN 0023ꢀ1584, Kinetics and Catalysis, 2010, Vol. 51, No. 6, pp. 809–815. © Pleiades Publishing, Ltd., 2010.
VIII INTERNATIONAL CONFERENCE
ON MECHANISMS OF CATALYTIC REACTIONS
Mechanistic Investigations of the Reaction Network in ChemoꢀBio
Catalyzed Synthesis of R
ꢀ1ꢀPhenylethyl Acetate1
,
e
A. Kirilina , S. Sahina, A. Tokareva, P. MäkiꢀArvelaa, K. Kordasb, A.ꢀR. Leinob, A. Shchukarevc,
,d
J.ꢀP. Mikkolaa , L. M. Kustove, T. Salmia, and D. Yu. Murzina
a Åbo Akademi University, Process Chemistry Centre, Turku/Åbo, Finland
bUniversity of Oulu, Oulu, Finland
cUmeå University, Applied Physics and Electronics/Energy Technology and Thermal Process Chemistry,
ChemicalꢀBiological Centre, Umeå, Sweden
dUmeå University, Department of Chemistry, Technical Chemistry, ChemicalꢀBiological Centre, Umeå, Sweden
eZelinsky Institute of Organic Chemistry, Moscow, Russia
eꢀmail: dmurzin@abo.fi
Received June 1, 2009
Abstract—The kinetics and reaction network of the oneꢀpot synthesis of
tigated at 70°C in toluene over a combination of three different catalysts: PdZn/Al2O3 as a catalyst for aceꢀ
tophenone hydrogenation, lipase as an enzymatic catalyst for ꢀ1ꢀphenylethanol acylation with ethyl acetate
and Ru/Al2O3 as a racemization catalyst for ꢀ1ꢀphenylethanol. In addition to the desired reactions, other
reactions, namely hydrogenolysis and dehydration of R, S)ꢀ1ꢀphenylethanol and debenzylation of R, S)ꢀ1
phenylethyl acetate also occurred. The kinetic results revealed that ethylbenzene formation was enhanced
with higher amounts of PdZn/Al2O3, whereas lipase did not catalyze ethylbenzene formation. Furthermore,
ethylbenzene was formed in the hydrogenolysis of (R, S)ꢀphenylethanol and in the debenzylation of R, S)ꢀ
ꢀphenylꢀethylacetate over Pd/Al2O3 catalyst. The presence of Ru/Al2O3 catalyst, in which Ru was in the oxiꢀ
dation state of ꢀ1ꢀphenylethyl acetate, although no clear racemization of
+, enhanced the formation of
ꢀ1ꢀphenylethanol during the oneꢀpot synthesis of ꢀ1ꢀphenylethyl acetate was observed. Dynamic kinetic
resolution of R, S)ꢀ1ꢀphenylethanol in toluene, was, however, demonstrated over Ru/Al2O3 and lipase.
Rꢀ1ꢀphenylethyl acetate was invesꢀ
R
S
(
(
ꢀ
(
1
3
R
S
R
(
DOI: 10.1134/S0023158410060054
1
Oneꢀpot synthesis is an important method aiming formed product, (R, S)ꢀ1ꢀphenylethanol, over Pd supꢀ
for process intensification and at the same time for
minimizing amount of waste, number of reactors and
required energy and to perform several reaction steps
in oneꢀpot over different catalysts without separation
and purification of the formed intermediates [1]. The
combining of chemoꢀbio catalyzed transformations,
especially hydrogenation with kinetic resolution is relꢀ
atively scarcely reported in literature [1]. Oneꢀpot synꢀ
ported catalysts. Recently a bimetallic catalyst selecꢀ
tive in acetophenone hydrogenation giving only small
amounts of ethylbenzene as a byꢀproduct was used [4].
Furthermore, there is a lack of an active and selective
racemization catalysts, which could afford more than
50% yield of the desired product. Supported Ru cataꢀ
lysts have been reported to be active in the dynamic
kinetic resolution of secondary alcohols, but racemꢀ
ization activity was declined in the presence of esters,
which are unavoidably present in oneꢀpot synthesis of
thesis of
nation of acetophenone, acylation of
anol and racemization of ꢀ1ꢀphenylethanol has been
R
ꢀ1ꢀphenylethyl acetate, involving hydrogeꢀ
Rꢀ1ꢀphenylethꢀ
S
already successfully demonstrated using a homogeꢀ
neous Schvo’s catalyst together with lipase [2]. The
benefits to use heterogeneous catalysts in the present
system would be, however, economic, since the homoꢀ
geneous metal complexes are usually expensive and
the catalyst separation and reuse is difficult.
Rꢀ1ꢀphenylethyl acetate [5].
The aim in this work was to elucidate the reaction
network of the oneꢀpot synthesis of Rꢀ1ꢀphenylethyl
acetate in the presence of a bimetallic hydrogenation
catalyst, PdꢀZn/Al2O3, an enzyme and a racemization
catalyst, Ru/Al Ru/Al2O3 (see Scheme). The emphaꢀ
sis is to reveal the interrelated functions of the different
catalysts.
Oneꢀpot synthesis of Rꢀ1ꢀphenylethyl acetate was
demonstrated starting from acetophenone hydrogenaꢀ
tion using both a Pd/Al2O3 catalyst and a lipase in the
same reactor [3]. One challenge in acetophenone
hydrogenation is to avoid hydrogenolysis of the
Oneꢀpot synthesis of
Rꢀ1ꢀphenylethyl acetate
1
The article is published in the original.
starting from acetophenone hydrogenation.
809

810
KIRILIN et al.
racemization catalyst
O
O
O
HO
HO
HO
H2
immobilized enzyme
acyl donor
+
+
hydrogenation
catalyst
H2
hydrogenation
catalyst
H2
hydrogenation catalyst
Scheme.
EXPERIMENTAL
(2 wt% Pd + 0.63 wt% Zn)/Al2O3 catalyst was preꢀ
The kinetic experiments were performed in a glass
reactor under flowing hydrogen (AGA, 99.999%). The
deoxygenated solvent (toluene) containing acetopheꢀ
none (Fluka) with the initial concentration of
0.02 mol/l, an immobilized lipase (Novozym 435)
(the mass in a range of 31–125 mg) and unreduced
4 wt % Ru/Al2O3 catalyst (100 mg) were added into
the reactor containing the inꢀsitu prereduced
pared according to [6] using the metal precursors
Zn(OAc)2 2H2O (220 mg, 1 mmol, Fluka, >99.5%)
and Pd(OAc)2 2H2O (224 mg, 1 mmol, SigmaꢀAldꢀ
⋅
⋅
rich, 99.9%). The complex was confirmed to be the
correct compound according to NMR 1H
(600.13 MHz, CDCl3): 2.02 (s, 4OAc). The catalyst
was prepared using incipientꢀwetness technique
according to [7] as follows: the above prepared comꢀ
Pd
metal supported catalysts exhibited the particle sizes
below 63 and the stirring rate was normally
⎯Zn/Al2O3 catalyst (the mass of 156–624 mg). The
µ
m
plex PdZn(OAc)4
⋅ H2O (82.6 mg) was dissolved in
500 rpm. The substrate to Pd molar ratio was 46.4,
23.3 and 11.6 in experiments with 156, 312, and
absolute ethanol (3 ml) at 25°C and the solution was
added dropwise to alumina (UOP, 1 g). This catalyst 624 mg of PdꢀZn/Al2O3, respectively. Some experiꢀ
was pretreated in argon flow with the following temꢀ ments were performed using 5 wt % Pd/Al2O3 with
perature programme: heating with 5°C/min velocity alumina from UOP and 5 wt % Pd/Al2O3 (Degussa) as
until 80°C (120 min) and thereafter reducing by a hydrogenation catalyst. Ethyl acetate with the conꢀ
centration of 0.06 mol/l was used as an acyl donor. In
addition to hydrogenation, also some experiments
were performed using (R, S)ꢀphenylethyl acetate
hydrogen with the same velocity until 250°C (60 min).
The hydrogen then was switched to argon and this
temperature was kept for 20 min with subsequent
cooling to room temperature. The catalyst 4 wt %
Ru/Al2O3 was prepared by the method described in [8]
using RuCl3 as a Ru source and alumina (UOP) as a
support.
(Acros, >98%) and
97%) as reactants.
(R, S)ꢀ1ꢀphenylethanol (Acros,
The initial catalytic activity was calculated using
the following equation:
The transmission electron microscopy (TEM)
measurements for determination of metal particle size
distributions were made with LEO 912 Omega, voltage
120 kV. Xꢀray diffraction (XRD) measurements were
Δn
ΔtmPd
,
rin =
where
n stands for molar amount of acetophenone
(mmol) converted within 30 min, t is time (min) and
made with Siemens D5000, Cu
K radiation. Nitrogen
α
mPd is mass of Pd (g).
adsorption measurements of specific surface areas of
the catalysts were performed with Carlo Erba (Sorpꢀ
tomatic 1900 Instruments). XPS spectra were
recorded with Kratos Axis Ultra electron spectrometer
equipped with a delay line detector. A monochroꢀ
The liquid phase samples were withdrawn from the
reactor after certain time intervals and analyzed with a
gas chromatograph containing a chiral column
(Supelco BexꢀDex 225 (length 30 m, diameter
250 μm, film thickness 0.25 μm) and a flame ionizaꢀ
tion detector using the following temperature proꢀ
mated Al
K source operated at 150 W. The binding
α
energy scale was referenced to the C 1s line of aliphatic
carbon, set at 285.0 eV. Processing of the spectra was gramme: 66°C (5 min)—heating 20°C/min
—111°C
accomplished with the Kratos software.
(10 min)—heating 20°C/min
—
190°C
.
KINETICS AND CATALYSIS Vol. 51
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MECHANISTIC INVESTIGATIONS OF THE REACTION NETWORK
811
H2 consumption, a.u.
Concentration, mol/l
0.020
2.5
2.0
1.5
1.0
0.5
0
137°C
0.015
1
2
0.010
0.005
242°C
336°C
3
4
0
5
0
50 100 150 200 250 300 350 400 450
, °C
0
100
200
300
400
500 600
Time, min
T
Fig. 1. Temperatureꢀprogrammed reduction profile for
Fig. 2. Kinetics of oneꢀpot synthesis of
acetate at 70°C: —acetophenone,
nol, ꢀ1ꢀphenylethanol, ꢀ1ꢀphenylethyl acetate,
—ethylbenzene. Conditions: 0.02 mol/l of acetopheꢀ
none, 0.06 mol/l of ethyl acetate in toluene as a solvent,
312 mg of (2 wt % Pd + 0.63 wt % Zn)/Al O , 125 mg of
R
ꢀ1ꢀphenylethyl
Ru/Al O .
1
2—Rꢀ1ꢀphenylethaꢀ
2
3
3—S
4—R
5
RESULTS AND DISCUSSION
2
3
lipase and 100 mg of 4 wt % Ru/Al O
2
3.
Alumina (UOP) used as a catalyst support exhibꢀ
ited low concentrations of the Br nsted and Lewis
ø
acid sites concentration (7 and 156 μmol/gcat, respecꢀ
tively) [9]. The BET specific surface area of the supꢀ
port was 306 m2/gcat. The average metal particle sizes
of (2 wt % Pd + 0.63 wt % Zn)/Al2O3 and 4 wt %
Ru/Al2O3 according to TEM measurements were
1.3 nm in both catalysts. There were no peaks detected
by XRD indicating that the metal particle sizes were
below 3 nm, which is the limit for detecting metal
crystallites with XRD. This result is in accordance
with the TEM results. XPS results for PdꢀZn/Al2O3
peaks can be assigned to changes occurred in the supꢀ
port morphology.
The kinetics of acetophenone hydrogenation was
studied by performing preliminary experiments showꢀ
ing the absence of external mass transfer limitations,
i.e., using different amounts of hydrogenation cataꢀ
lysts and small catalyst particles. A typical reaction
kinetics from oneꢀpot synthesis of
Rꢀ1ꢀphenylethyl
acetate, in which acetophenone was hydrogenated
within 535 min to 99% conversion, is shown in Fig. 2.
catalyst revealed that the binding energies for Pd
3d5/2
As primary products, both
were formed as racemates. Thereafter,
anol is acylated to ꢀ1ꢀphenylethyl acetate, with a very
Sꢀ
and
R
ꢀ1ꢀphenylethanol
and for Pd d3/2 region varied from 334.3 to 335.5 eV
3
Rꢀ1ꢀphenylethꢀ
and from 339.6 to 340.8 eV, respectively, whereas for
metallic Pd the binding energy of 335.0 eV has been
reported in literature [10] thus suggesting that in the
current work Pd is in any case partially in metallic
form. The peak broadness for metallic palladium
should be, however, 1.50 eV, whereas in this case the
peaks are broader (2.4 eV) suggesting PdꢀZn alloy forꢀ
mation [11].
R
low initial rate, since the latter compound was
detected only after 25 min of reaction. After 535 min
of reaction the selectivity to
Rꢀ1ꢀphenylethyl acetate
was 26% at the conversion level of 99%.
From the concentration profile of ꢀ1ꢀphenylethaꢀ
S
nol it cannot be clearly stated, whether minor racemꢀ
ization occurred or not under these reaction condiꢀ
Ru/Al2O3 was used under argon or under hydrogen
in the racemization of (R, S)ꢀ1ꢀphenylethanol and
thereafter the spent catalysts were investigated using
XPS. The spectra of these two catalysts showed that
tions over Ru/Al2O3, since the concentration of
phenylethanol did not decrease during the course of
the reaction. Dynamic kinetic resolution of R, S)ꢀ1
Sꢀ1ꢀ
(
ꢀ
phenylethanol was, however, possible over this catalyst
in toluene at 70°C in the presence of three equivalents
Ru
and 484.5–484.8 eV, respectively. According to the litꢀ
erature the binding energies for Ru p3/2 and Ru p1/2
3p3/2 and Ru 3p1/2 were in the range of 462.3–462.6
of ethyl acetate: 11% of inactive isomer
nol was converted to ꢀ1ꢀphenylethyl acetate via raceꢀ
mization and further resolution reaction. Therefore,
the final concentration of target ꢀ1ꢀphenylethyl aceꢀ
Sꢀphenylethaꢀ
3
3
R
corresponding to Ru(III) are 462.9 and 484.8 eV,
respectively [12], which is consistent with present
data. Temperatureꢀprogrammed reduction profile for
Ru/Al2O3 is shown on Fig. 1. The first peak can be
R
tate (0.0105 mol/l) exceeded the value expected from
only kinetic resolution (0.094 mol/l) by 11% at 94%
attributed to reduction of Ru, whereas the other two conversion of initial
Rꢀ1ꢀphenylethanol as demonꢀ
KINETICS AND CATALYSIS Vol. 51
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2010

812
KIRILIN et al.
Table 1. Kinetic results of oneꢀpot synthesis of
of amounts of Pd/Al2O3 and lipase
Rꢀ1ꢀPEAc starting from acetophenone hydrogenation in dependence
Selectivity
to ꢀPEAc, %
Selectivity
to ethylbenzene, %
Mass Mass
Entry of Pd/Al2O3, of lipase,
rin
,
R
Conversion
after 360 min, %
mmol min–1 gP–d1
at 50% at 90% at 50% at 90%
conversion conversion conversion conversion
mg
mg
1
2
3
4
5
6
156
312
624
624
312
312
62.5
62.5
62.5
125
31
2.8
2.8
3.2
3.0
2.4
3.2
70
91
95
92
84
90
26
18
10
10
16
24
–
3
3
–
26
18
25
19
27
14
23
22
19
14
4
20
7
125
2
Note: Initial concentration of acetophenone 0.02 mol/l, 70°C, solvent toluene, 3 equivalents of ethyl acetate as an acyl donor over
(2 wt % Pd + 0.63 wt % Zn)/Al O . The amount of racemization catalyst 4 wt % Ru/Al O was 100 mg.
2
3
2 3
strated in [13]. The active species of ruthenium was conversion after 360 min was achieved with the
Ru(III), since Ru was not reduced under reaction Pd/lipase ratio of 2.5 being only 70%, whereas with
conditions, as revealed from TPR (Ru is reduced at higher ratios, namely 5 and 10, the difference in the
137°C, which is much higher than reaction temperaꢀ conversion levels was not large. Thus it can be conꢀ
ture). Sꢀ1ꢀphenylethanol reacted further principally in cluded that in order to achieve high conversions an
several ways, i.e., via dehydration, and racemization. excess of a hydrogenation catalyst should be used.
In a separate experiment over a monometallic
The formation of Rꢀ and Sꢀ1ꢀphenylethanol was
racemic with equal amounts of both alcohols. When
increasing the amount of the hydrogenation catalyst,
Pd/Al2O3 catalyst in the presence of hydrogen it was
shown that even hydrogenolysis of secondary alcohols
produced ethylbenzene. Additionally Pd/Al2O3 cataꢀ
higher concentrations of
achieved, as expected. Furthermore, a maximum conꢀ
centration was achieved for ꢀ1ꢀphenylethanol after
Rꢀ1ꢀphenylethanol were
lyzed debenzylation of
(R, S)ꢀ1ꢀphenylethanol formꢀ
ing ethylbenzene was confirmed.
R
Ethylbenzene was formed, as explained above, via 210, 175, and 70 min corresponding to the amounts of
several reactions, namely debenzylation of an ester, PdꢀZn/Al2O3 catalyst 156, 312, and 624 mg, respecꢀ
dehydration or hydrogenolysis of secondary alcohols. tively. These maximum concentrations were 0.0020,
The initial rate of ethylbenzene formation was only 0.0023, and 0.0034 mol/l, respectively. The concenꢀ
22% of the rate achieved after 160 min reaction time. tration profiles for
This result indicated that ethylbenzene formation was 312 mg of PdꢀZn/Al2O3 catalyst were monotonically
enhanced with increasing reaction time, when more increasing with time, whereas a maximum in ꢀ1ꢀpheꢀ
primary and secondary products were formed. nylethanol concentration was achieved using 624 mg
of this catalyst. This result indicated that the formaꢀ
Rꢀ1ꢀphenylethanol using 156 and
S
Kinetics of the oneꢀpot synthesis of ꢀ1ꢀphenylꢀ
R
tion rate of ꢀ1ꢀphenylethanol was higher than its
S
ethyl acetate was systematically investigated by varying
the amounts of the hydrogenation and the acylation
catalysts (Table 1). The initial hydrogenation activities
were calculated as moles of converted acetophenone
per amount of Pd, since the hydrogenation activity of
zinc was very minor (see below), and Ru was in the
oxidation state 3+ not effective in hydrogenation.
When the amounts of the hydrogenation catalyst
increased (Table 1, entries 1–3), the rin slightly
increased. When the ratio between Pd and lipase
consumption rate and thus racemization and dehydraꢀ
tion or hydrogenolysis rates of ꢀ1ꢀphenylethanol
S
were relatively small with lower amounts of Pdꢀ
Zn/Al2O3. When 624 mg of PdZn/Al2O3 catalyst was
used in oneꢀpot synthesis of
Rꢀ1ꢀphenylethyl acetate,
also the formation of ethylbenzene was enhanced thus
giving as a result a maximum concentration of
phenylethanol after 442 min.
Sꢀ1ꢀ
The formation rates of the desired product,
Rꢀ1ꢀ
increased, higher hydrogenation rates were achieved. phenylethyl acetate
(RꢀPEAc), increased with
This result is in accordance with the earlier data [14], decreasing amount of the hydrogenation catalyst from
showing that the hydrogenation rate was slightly 624 to 312 and further to 156 mg (Fig. 3a). At the same
higher in the absence of lipase compared to its presꢀ time the selectivities to
Rꢀ1ꢀphenylethyl acetate
ence. The conversion of acetophenone increased, as increased with decreasing amount of PdZn/Al2O3
expected, after prolonged reaction times when using (Table 1, entries 1–3). At higher amounts of the
larger amounts of PdZn/Al2O3 catalyst. The lowest hydrogenation catalyst (624 mg) the ethylbenzene forꢀ
KINETICS AND CATALYSIS Vol. 51
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2010

MECHANISTIC INVESTIGATIONS OF THE REACTION NETWORK
813
mation was enhanced, especially from secondary alcoꢀ
hols, thus lowering the yield of ꢀ1ꢀphenylethyl aceꢀ
tate. A maximum of the concentration of ꢀ1ꢀphenylꢀ
ethyl acetate was achieved after 285 min reaction time,
thereafter ester debenzylation was observed. When
[RꢀPEAc], mol/l
R
0.006
0.004
0.002
0
R
(a)
2
1
R
ꢀ1ꢀphenylethyl acetate concentration was plotted as
a function of acetophenone conversion (Fig. 3a), it
can be clearly seen that ester formation is a consecuꢀ
tive reaction.
3
Ethylbenzene formation was extensively enhanced
with a large amount of PdZn/Al2O3 catalyst (Table 1).
After 400 min of reaction time the selectivity to ethylꢀ
benzene with 624 mg of PdꢀZn/Al2O3 was 46% at the
conversion level of 97%. In order to understand a role
of active metal and support in this reaction, an addiꢀ
tional experiment was performed using (R, S)ꢀ1ꢀpheꢀ
0
20
40
60
80
100
nylethanol as a reactant over Al2O3 powder. The result
was the absence of any transformation of secondary
alcohol at 70°C in ethylacetate as a solvent. Thus, it
can be concluded that the formation of ethylbenzene
was catalyzed by Pd.
In the second series (Fig. 3b), when the amounts of
the hydrogenation catalyst and the racemization cataꢀ
lyst were kept constant, namely 312 and 100 mg,
respectively, the lipase amount was varied being 31,
62.5, and 125 mg (Table 1, entries 5, 2, and 6) with
increasing amount of lipase. The initial hydrogenation
rates were very close to each other, as expected.
Slightly lower conversion of acetophenone was
achieved with lower amount of lipase, being, however,
within the reproducibility limits. From the mechanisꢀ
tic point of view the hydrogenation rate should not be
affected by the presence of enzyme.
0.006
0.004
0.002
0
(b)
2
3
1
0
20
40
60
80
100
Conversion, %
As expected, the product distribution related to
acylation was very prominently affected by the amount
of lipase. Different maxima in the concentration for
Fig. 3. Formation of Rꢀ1ꢀphenylethyl acetate as a function
of acetophenone conversion at initial concentration of
acetophenone 0.02 mol/l, 70°C, solvent toluene, 3 equivꢀ
alents of ethyl acetate as an acyl donor. (a) 100 mg of 4 wt
R
ꢀ1ꢀphenylethanol were achieved as a function time
%
Ru/Al O and 62.5 mg of lipase together with (
1
) 156,
with different amounts of lipase (31, 62.5, and
125 mg). The corresponding maximum concentraꢀ
tions were 0.0027, 0.0023, and 0.0021 mol/l, respecꢀ
tively.
2
3
(
2
) 312, and (
3) 624 mg of PdꢀZn/Al O . (b) 312 mg of
2
3
PdꢀZn/Al O and 100 mg of Ru/Al O together with
(1) 31, (2) 62, and (3) 125 mg of lipase.
2
3
2 3
Thereafter
either to ester or to ethyl benzene.
Rꢀ1ꢀphenylethanol reacted further,
est amount of lipase, i.e., 31 mg. The selectivities to
Rꢀ
1ꢀphenylethyl acetate increased also with increasing
The concentration profiles for
Sꢀ1ꢀphenylethanol
lipase amounts (Table 1, entries 5, 2, and 6), while the
opposite was shown for ethylbenzene. Its formation
decreased with increasing amount of lipase, when the
amounts of the hydrogenation catalyst and the racemꢀ
ization catalyst were constant (Table 1, entries 5, 2,
and 6). Thus, it can be concluded that there is an
increased with increasing time with all three amounts
of lipase, since the ethylbenzene formation was not
catalyzed very effectively. Furthermore, the racemizaꢀ
tion rate, which cannot be separated from the kinetic
data due to the formation of ethylbenzene, could not
be, however, very significant, since Sꢀ1ꢀphenylethanol
production was larger during the reaction than its furꢀ interrelation between the two catalysts, namely
ther reaction to either
benzene.
The formation of the desired product,
nylethanol, was a consecutive reaction, which could
be seen from the shapes of its concentration profiles
R
ꢀ1ꢀphenylethanol or ethylꢀ
between the hydrogenation catalyst and the enzyme,
since the ethylbenzene formation, which is catalyzed
by Pd (hydrogenolysis or dehydration of a secondary
alcohol and debenzylation of the desired product), was
enhanced with a smaller amount of lipase. The cataꢀ
lytic effect of Pd in debenzylation is thus more promiꢀ
Rꢀ1ꢀpheꢀ
(Fig. 3b). The lowest concentration of
Rꢀ1ꢀphenylꢀ
ethyl acetate was achieved, as expected, using the lowꢀ nent in the presence of only small lipase amounts. At
KINETICS AND CATALYSIS Vol. 51
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2010

814
KIRILIN et al.
Table 2. Kinetic results of oneꢀpot synthesis of
in the presence of the racemization catalyst 4 wt % Ru/Al2O3
Rꢀ1ꢀPEAc starting from acetophenone hydrogenation in the absence and
Selectivity to
at 50%
conversion conversion
RꢀPEAc, % Selectivity to ethylbenzene, %
rin
,
Mass
of Ru/Al2O3, mg
Conversion
after 360 min, %
mmol min–1 gP–d1
at 85%
at 50%
conversion
at 85%
conversion
0
3
89
85
16
21
24
31
10
10
6
6
100
2.6
Note: Initial concentration of acetophenone 0.02 mol/l, 70°C, solvent toluene, 3 equivalents of ethyl acetate as an acyl donor over 5 wt %
Pd/Al O , 127 mg of the hydrogenation catalyst together with 62.5 mg lipase.
2
3
the same time the concentration of
acetate decreased.
R
ꢀ1ꢀphenylethyl
Thus, the reaction network in oneꢀpot synthesis of
ꢀ1ꢀphenylethyl acetate was investigated using
PdZn/Al2O3 as a hydrogenation catalyst, a lipase as an
acylation catalyst and Ru/Al2O3 as a racemization catꢀ
R
The effect of the racemization catalyst, Ru/Al2O3
,
was investigated using 5 wt % Pd/Al2O3 as a hydrogeꢀ
nation catalyst together with lipase for acylation. Two
experiments were performed in oneꢀpot synthesis of
alyst. Besides the desired
ethylbenzene was formed via hydrogenolysis of
ꢀphenylethanol as well as through debenzylation of
R, S)ꢀ1ꢀphenylethyl acetate. Racemization of ꢀ1
R
ꢀ1ꢀphenyethylacetate, also
(R, S)ꢀ
1
(
Rꢀ1ꢀphenylethyl acetate starting from acetophenone
S ꢀ
hydrogenation, in the absence and in the presence of
Ru/Al2O3 in toluene with three equivalents of ethylacꢀ
etate as an acyl donor at 70°C (Table 2). The results
showed that the hydrogenation rates were close to each
other indicating that Ru/Al2O3 is not active in the
hydrogenation, as expected, since it is in the oxidation
state of 3+ and is not reduced during the reaction. The
phenylethanol in oneꢀpot synthesis was not prominent
in the presence of esters, i.e., an acyl donor itself and
the desired product,
although dynamic kinetic resolution of
R
ꢀ1ꢀphenylethyl acetate,
(R, S)ꢀ1ꢀpheꢀ
nylethanol over Ru/Al2O3 and lipase in toluene, was
successfully demonstrated. The presence of Ru/Al2O3
together with PdZn/Al2O3 and lipase exhibited a posꢀ
itive effect on the formation of Rꢀ1ꢀphenylethyl aceꢀ
tate compared with the absence of the racemization
catalyst.
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. Kriszꢀ
tian Kordas is acknowledging the Academy of Finland
for funding (120853, 124357, 128626).
highest concentrations of both Rꢀ and Sꢀ1ꢀphenylethꢀ
anol were achieved over the catalytic system containꢀ
ing no racemization catalyst. Ethylbenzene formation
was the same in the presence and in the absence of Ru
catalyst, but a positive effect of the racemization cataꢀ
lyst was observed in the presence of Ru/Al2O3: about
24% higher selectivity to the desired product was
achieved at 50% conversion of acetophenone. Since
the concentration profiles for
showed no decreasing trend as a function of time, it is
difficult to determine the efficiency of ꢀ1ꢀphenylethꢀ
Sꢀ1ꢀphenylethanol
S
anol racemization. Furthermore, it was stated [5] that
esters inhibit Ru activity as a racemization catalysts
and their presence in this oneꢀpot synthesis, cannot be
avoided.
In the hydrogenation of acetophenone, the effect
of zinc on the formation of ethylbenzene was investiꢀ
gated. 5 wt % Zn/Al2O3 exhibited minor activity in
acetophenone hydrogenation. Oneꢀpot experiments
with either 5 wt % Pd/Al2O3 or (2 wt % Pd + 0.63 wt %
Zn)/Al2O3 and the same Pd/acetophenone ratio
showed that the hydrogenation rates and the formaꢀ
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