Heterogeneous enantioselective hydrogenation in a continuousflow fixed-bed reactor system: Hydrogenation of activated ketones and their binary mixtures on pt-alumina-cinchona alkaloid catalysts

Article abstract of DOI:10.1007/s10562-012-0846-9

Under the experimental conditions of the Orito reaction the individual hydrogenation and the competitive hydrogenations of three binary mixtures of methyl benzoylformate (MBF), pyruvic aldehyde dimethyl acetal (PA) and 2,2-diethoxyacetophenone (DAP) on platinum-alumina catalysts modified by cinchonidine, cinchonine, quinine and quinidine (Pt-CD, Pt-CN, Pt-QN, Pt-QD) were studied for the first time using continuous-flow fixed-bed reactor system. Conversions of chiral (Cc) and racemic (Cr) hydrogenations of all three compounds and enantioselectivities (ee) were determined under the same experimental conditions (under 4 MPa H2 pressure, at room temperature using toluene/AcOH 9/1 as solvent).The order of the rates of the enantioselective hydrogenations of the three substrates studied is MBF > PA > DAP, and the order of their ee values is MBF ? PA > DAP. The hydrogenation rate and the effect of rate on ee depend on the structure of the cinchona used: hydrogenation of MBF and PA may produce ee values over 90 %, however, the ee values were conspicuously low in the presence of Pt-QN and especially of Pt-QD catalysts. In the chiral hydrogenation of DAP considering racemic hydrogenation rate decrease (Cc/Cr < 1) takes place instead of rate enhancement over all four catalysts. The new experimental data supported the so far known fundamental rules of the Orito reaction based on batch studies. Springer Science+Business Media, LLC 2012.

Full text of DOI:10.1007/s10562-012-0846-9

Catal Lett (2012) 142:889–894
DOI 10.1007/s10562-012-0846-9
Heterogeneous Enantioselective Hydrogenation in a Continuous-
flow Fixed-bed Reactor System: Hydrogenation of Activated
Ketones and Their Binary Mixtures on Pt–Alumina–Cinchona
Alkaloid Catalysts
Gy o¨ rgy Sz }o ll }o si
•
Zsolt Makra
•
M o´ nika Fekete
•
Ferenc F u¨ l o¨ p
•
Mih a´ ly Bart o´ k
Received: 17 January 2012 / Accepted: 10 May 2012 / Published online: 30 May 2012
Ó Springer Science+Business Media, LLC 2012
Abstract Under the experimental conditions of the Orito
reaction the individual hydrogenation and the competitive
hydrogenations of three binary mixtures of methyl ben-
zoylformate (MBF), pyruvic aldehyde dimethyl acetal (PA)
and 2,2-diethoxyacetophenone (DAP) on platinum–alu-
mina catalysts modified by cinchonidine, cinchonine, qui-
nine and quinidine (Pt–CD, Pt–CN, Pt–QN, Pt–QD) were
studied for the first time using continuous-flow fixed-bed
reactor system. Conversions of chiral (C ) and racemic (C )
considering racemic hydrogenation rate decrease (C /Cr
c
\ 1) takes place instead of rate enhancement over all four
catalysts. The new experimental data supported the so far
known fundamental rules of the Orito reaction based on
batch studies.
Keywords Cinchona alkaloid ꢀ
Competitive hydrogenations ꢀ Enantioselective ꢀ
Methyl benzoylformate ꢀ Pyruvaldehyde dimethyl acetal ꢀ
2,2-Diethoxyacetophenone ꢀ Pt–alumina ꢀ
Continuous-flow reactor
c
r
hydrogenations of all three compounds and enantioselec-
tivities (ee) were determined under the same experimental
conditions (under 4 MPa H pressure, at room temperature
2
using toluene/AcOH 9/1 as solvent).The order of the rates
of the enantioselective hydrogenations of the three sub-
strates studied is MBF [ PA [ DAP, and the order of their
ee values is MBF * PA [ DAP. The hydrogenation rate
and the effect of rate on ee depend on the structure of the
cinchona used: hydrogenation of MBF and PA may pro-
duce ee values over 90 %, however, the ee values were
conspicuously low in the presence of Pt–QN and especially
of Pt–QD catalysts. In the chiral hydrogenation of DAP
1 Introduction
The heterogeneous enantioselective hydrogenation of pro-
chiral ketones is one of the most important methods for the
synthesis of chiral secondary alcohols [1–7]. Besides the
widespread application of batch reactors the continuous-
flow fixed-bed reactor system (CFBR) has also been uti-
lized in the chiral hydrogenation of activated ketones
[
8–12], mainly to study the mechanism of the Orito reac-
tion [13–17] and in lesser extent to the practical realization
of the reactions [18, 19].
G. Sz }o ll }o si (&) ꢀ F. F u¨ l o¨ p ꢀ M. Bart o´ k (&)
Stereochemistry Research Group, The Hungarian Academy
of Sciences, D o´ m t e´ r 8, Szeged 6720, Hungary
e-mail: szollosi@chem.u-szeged.hu
Competitive hydrogenation of ketone mixtures over metal
catalysts is a widely used method in studies on the mecha-
nism of their surface transformations [20, 21]. Research on
competitive hydrogenations has yielded new information on
the effect of the electronic and 3D structure of the substrates
on adsorption and on surface reactions [22]. In the compet-
M. Bart o´ k
e-mail: bartok@chem.u-szeged.hu
Z. Makra ꢀ M. Fekete ꢀ M. Bart o´ k
Department of Organic Chemistry, University of Szeged,
D o´ m t e´ r 8, Szeged 6720, Hungary
itive chiral hydrogenation (C = conversion of chiral
c
hydrogenation) over cinchonidine (Pt–CD) chiral catalyst of
(
diethoxyacetophenone) DAP ? PA (pyruvic aldehyde
F. F u¨ l o¨ p
Institute of Pharmaceutical Chemistry, University of Szeged,
E o¨ tv o¨ s u 6, Szeged 6720, Hungary
dimethyl acetal) binary mixture the PA is hydrogenated
faster than DAP, whereas in racemic hydrogenation
123

8
90
G. Sz }o ll }o si et al.
OH
R
O
OH
S
+
X
H , Pt, solvent
+H , Pt, solvent
OMe
2
OMe
2
OMe
Ph
Ph
Ph
CN or QD
CD or QN
O
O
O
MBF
3
3
N
N
OH
HO
S
9
S
8
H
8
H
R
H
H
R
9
6'
6' X
N
N
X = H: cinchonidine (CD)
X = OMe: quinine (QN)
X = H: cinchonine (CN)
X = OMe: quinidine (QD)
OH
R
O
OH
S
+
H , Pt, solvent
+H , Pt, solvent
OR'
OR'
2
OR'
2
OR'
OR'
R
R
R
CD or QN
CN or QD
OR'
PA: R = R' = Me
DAP: R = Ph, R' = Et
Scheme 1 The Orito reaction of MBF, PA and DAP
(
C = conversion of racemic hydrogenation) the DAP is
r
under air beforeuse [25, 26]. ThepropertiesofE4759catalyst:
Pt-content, 5 % (w/w); Pt dispersion (after pretreatment),
25 %; mean Pt particle size, 4.4 nm.
hydrogenated faster than PA [23]. In view of this unexpected
experimental observation, it seemed expedient to study the
competitive hydrogenation of binary activated ketone mix-
tures in the CFBR system not only over Pt–CD, but using
cinchonine (Pt–CN), quinine (Pt–QN) and quinidine
2.2 Hydrogenations in Flow System (CFBR)
(
Pt–QD) chiral catalyst, too.
Continuous hydrogenations were carried in H-cube high-
pressure continuous-flow system. The experimental set-up
has been described in detail in our previous publication
[14]. The same catalyst was used per measurement cycle
(of 160 min) washing the catalyst for 1 h between substrate
exchanges (S1, S2, S1 ? S2, S1). A typical series of
measurement began with pre-hydrogenation of the catalyst
(60 min), continued with chiral hydrogenation of individ-
ual substrates and followed by chiral hydrogenation of
binary mixture. The measurement series were ended by
hydrogenation of the first substrate. The purpose of the
latter was to monitor the deactivation of the catalyst in the
course of the measurement cycle.
The objective of the present research was to study the
hydrogenation of 3 binary mixtures of the activated
ketones shown in Scheme 1, i.e. (methyl benzoylformate)
MBF ? PA, MBF ? DAP and PA ? DAP, under the
experimental conditions of the Orito reaction. Comparison
of the experiments on Pt–alumina catalyst modified by
parent cinchona alkaloids was the main goal. The present
studies on the hydrogenation of these binary mixtures
confirmed the unexpected experimental observation
obtained using the batch method [24].
2
Experimental
Standard conditions were: 50 mg E4759 catalyst, 293 K,
4
MPa hydrogen pressure, solvent: toluene/AcOH 9/1,
-
1
2
.1 Materials
liquid flow 1 mL min , modifier concentration: 0.44 mM,
substrate concentration 11 mM. In our earlier experiments
we verified that our measurements proceed in a kinetic
regime [14], which is also confirmed by the high ee values,
since it is well-known that mass transfer limitations can
dramatically decrease ee values [4]. Conversions (C) and
enantiomeric excesses, ee % = |[R]-[S]| 9 100/([R]?[S]),
were determined by gas chromatography (HP 6890 N
GC-FID, 30 m Cyclodex-B chiral capillary column). The
reproducibility of the results was ± 2 %.
Cinchona alkaloids (CD, CN, QN, QD), activated ketones
studied (MBF, PA, DAP) and solvents were purchased from
Aldrich or Fluka. MBF, PA and DAP were distilled under
vacuum using a Vigreux-column. Engelhard 5 % Pt/Al O
2
3
(
E4759) was pretreated in a fixed-bed reactor by flushing with
-1
-1
3
0 mL min He at 300–673 K for 30 min and 30 mL min
H at673 Kfor100 min. Aftercoolingtoroomtemperaturein
2
H the catalyst was flushed with He for 30 min and was stored
2
1
23

Enantioselective Hydrogenation in Continuous System
891
1
00
100
80
60
40
20
0
DAP [23, 27]. However, no experimental observations on
the competitive hydrogenation of these substrates and their
binary mixtures have been reported yet in the CFBR using
Pt–QN, Pt–CN and Pt–QD chiral catalysts.
PA
8
6
4
2
0
0
0
0
0
PAi
DAPi
DAPm
3.1 Enantioselective Hydrogenation of PA, DAP
and Their Binary Mixture: Dependence
PAm
of Conversion and ee on Modifier Concentration
PAiF
DAPi
In our previous work we studied in CFBR the competitive
hydrogenation of binary mixtures of activated ketones over
CD-modified (0.44 mM) Pt catalyst [23]. Our further aim
was to elucidate the effect of the chiral modifier concen-
tration on conversion and enantioselectivity. The experi-
mental data obtained with PA and DAP are shown in
Fig. 1.
DAPm
0
0.01
0.1
0.44
2
[CD]
Fig. 1 Enantioselective hydrogenation of PA, DAP and their binary
mixture: effect of the modifier concentration on the conversion
In batch reactor strong increase with maximum or
saturation-type dependence for both rate and enantiose-
lectivity were observed as a function of modifier concen-
tration for hydrogenation of ethyl pyruvate and ethyl
benzoylformate. It was plausible to assume that CD is
adsorbed stronger than either solvent or the substrate [30].
Studies of this type have been carried out with PA [29];
however, no results have been published using DAP, not
even for batch measurements.
(closed symbols) and on ee (open symbols); (subscript i individual,
m mixture, iF final individual hydrogenation, see Sect. 2.2)
3
Results and Discussion
Hydrogenation of activated ketones over Pt–CD catalysts
under the conditions of the Orito reaction in a batch reactor
has been discussed in numerous reviews [4–7]. The
majority of the reports were studies of ethyl pyruvate, a
smaller fraction investigates MBF, whereas only very few
publications report experiments on PA [23, 27–29] and
The data in Fig. 1 allow the following conclusions to be
drawn:
Table 1 Conversion of hydrogenations of individual substrates (CSi) and of competitive hydrogenations of binary mixtures (CSm) and enan-
tiomeric excesses (ee, %) obtained over chiral catalyst (Pt–M) using the CFBR system
Individual hydrogenation
Conversion (%)
Hydrogenation of binary mixtures
Conversion (%) ee (%)
ee (%)
eeS1i
S1 ? S2
M
C
S1i
C
S2i
eeS2i
C
S1m
C
S2m
eeS1m
eeS2m
MBF ? PA
MBF ? PA
MBF ? PA
MBF ? PA
MBF ? PA
MBF ? DAP
MBF ? DAP
MBF ? DAP
MBF ? DAP
MBF ? DAP
PA ? DAP
PA ? DAP
PA ? DAP
PA ? DAP
PA ? DAP
–
80
95
94
83
73
87
95
93
96
67
8
8
–
–
68
88
93
78
66
80
90
86
94
63
7
4
–
–
CD
QN
CN
QD
–
53
37
30
17
30
20
5
89 (R)
54 (R)
63 (S)
23 (S)
–
90 (R)
86 (R)
64 (S)
52 (S)
–
38
32
18
8
87 (R)
62 (R)
62 (S)
25 (S)
–
90 (R)
85 (R)
73 (S)
53 (S)
–
17
12
3
CD
QN
CN
QD
–
92 (R)
61 (R)
66 (S)
18 (S)
–
77 (R)
8 (R)
49 (S)
8 (S)
–
92 (R)
63 (R)
67 (S)
19 (S)
–
77 (R)
8 (R)
48 (S)
5 (S)
–
9
7
4
3
35
14
4
31
10
3
CD
QN
CN
QD
54
28
37
17
90 (R)
82 (R)
68 (S)
52 (S)
76 (R)
7 (R)
40 (S)
6 (S)
40
18
23
9
91 (R)
82 (R)
72 (S)
44 (S)
76 (R)
3 (R)
40 (S)
6 (S)
6
4
4
3
-
1
Reaction conditions: 50 mg Pt/Al
M) concentration: 0.44 mM, substrate concentration: 11 mM; subscript i hydrogenation of the individual substrate, m hydrogenation of the
substrate in binary mixture
2 3 2
O (E4759) catalyst, 293 K, 4 MPa H pressure, solvent: toluene/AcOH 9/1, liquid flow 1 mL min , modifier
(
123

8
92
G. Sz }o ll }o si et al.
(
a) 100
(i) Continuous deactivation of the catalyst is observed
with the advancement of measurement time, as verified by
the comparison of the first and last measurements of the
series. (ii) In hydrogenations of both substrates (PA and
DAP) C [ C and ee [ ee , which can be explained by
the higher concentration and/or faster conversion of the
surface complex responsible for chiral induction. (iii)
Conversion as well as ee increase continuously with
modifier concentration in the case of both the individual
substrates and their mixtures (with the exception of race-
mic hydrogenations of DAP). (iv) Just like the chiral
hydrogenation of the majority of activated ketones, that of
PA also proceeds according to the ‘‘ligand acceleration’’
8
6
4
2
0
0
0
0
0
PAi
MBFi
PA ,
m
MBFm
i
m
i
m
PAi
0
40
80
120
160
(LA) mechanism [19]; in the chiral hydrogenation of DAP,
Time on stream (min)
however, a rate decrease (‘‘ligand deceleration’’) was
observed instead of rate enhancement.
(
b) 100
A chiral modifier concentration of 0.44 mM was chosen
for further measurements in spite of the fact that, according
to the experimental data shown in Fig. 1, the 2 mM con-
centration was somewhat more favorable. The reason for
our choice was to make possible the comparison of the new
experimental data with the previous CFBR measurements
performed at a cinchona concentration of 0.44 mM.
8
6
4
2
0
0
0
0
0
PAi
DAPi
PA
DAPm
,
m
PAi
3.2 Enantioselective Hydrogenation of Individual
Substrates and Their Binary Mixtures
Results of the measurements are presented in Table 1, and
typical measurement series are shown as examples in
Fig. 2. Fig. 2a presents a hydrogenation associated with an
outstandingly high ee (MBF, PA, Pt–CD catalyst), whereas
Fig. 2b, c shows chiral hydrogenations of the rarely studied
substrates PA and DAP over Pt–CD and Pt–CN catalysts.
According to Fig. 2, catalyst activity is somewhat dimin-
ished with the progress of reaction time. Deactivation is
mainly the consequence of the substrates side reactions
0
40
80
120
160
Time on stream (min)
(
c) 100
8
6
4
2
0
0
0
0
0
PA ,
DAPm
PAi
m
DAPi
(decomposition accompanied by carbonaceous deposition
PAi
and CO formation) [4, 31, 32]. Due to the character of the
measurement, steady state cannot be reached within the
hydrogenation time of 160 min. Some of the conversion
data (C ) in Table 1 indicate inconsistent reproducibility:
Si
it is well-known that catalyst systems treated with chiral
modifiers are somewhat more sensitive than unmodified
hydrogenation catalysts. The reason for this is, among
others, that depending on the initial state of the catalyst, the
chiral modifier brings about dynamic and continuous
changes in the structure of the active sites [28, 33–40]. This
effect of the modifier also depends on its irreversible
adsorption under the different conditions of the reactions
0
40
80
120
160
Time on stream (min)
Fig. 2 Conversions (closed symbols) and ees (open symbols) as a
function of time on stream obtained in the enantioselective hydro-
genation of a PA and MBF; b PA and DAP over Pt–CD catalyst and
c PA and DAP over Pt–CN catalyst (under standard conditions,
subscript i individual hydrogenation, m hydrogenation of the two
activated ketone mixture)
[
34, 41, 42].
1
23

Enantioselective Hydrogenation in Continuous System
893
Table 2 Data calculated from Table 1
S1 ? S2
M
C
S1i/CS2i
C
S1m/CS2m
C
S1i/m
C
S2i/m
eeS1i/m
eeS2i/m
C
c
/C
r
S1
i
S2
i
MBF ? PA
MBF ? PA
MBF ? PA
MBF ? PA
MBF ? DAP
MBF ? DAP
MBF ? DAP
MBF ? DAP
PA ? DAP
PA ? DAP
PA ? DAP
PA ? DAP
CD
QN
CN
QD
CD
QN
CN
QD
CD
QN
CN
QD
1.8
2.5
2.8
4.2
4.8
18
11
17
4
2.3
2.9
4.3
8.3
7.5
29
13
21
4
1.1
1.0
1.1
1.1
1.1
1.1
1.0
1.1
1.4
1.6
1.6
1.9
1.7
1.2
1.7
2.1
1.7
1.7
1.3
1.3
1.4
1.3
1.5
1.3
1.0
0.9
1.0
0.9
1.0
1.0
1.0
1.0
1.0
1.0
0.9
1.2
1.0
1.0
0.9
1.0
1.0
1.0
1.0
1.6
1.0
2.0
1.0
1.0
1.2
1.2
1.0
0.9
1.1
1.1
1.1
0.8
6.8
3.5
4.6
2.1
6.6
4.6
3.8
2.1
0.6
0.1
0.3
0.1
0.4
0.1
0.1
0.1
7
6
6
5.8
3
4
c r
For abbreviations see Table 1; C /C = ratio of conversions of chiral and racemic hydrogenation
The experimental data in Tables 1, 2 and Fig. 2 lead to
several conclusions related to the hydrogenations of MBF,
PA and DAP under the same experimental conditions.
Pt–CD but over Pt–QN, CN, QD catalysts rate enhance-
ment takes place too (the values of C /C [ 1) in the chiral
c
r
hydrogenation of the PA; however, a rate decrease is
(
i) The order of the rates of the enantioselective hydroge-
observed (C /C \ 1) in the DAP hydrogenation, which
c
r
nations of the three substrates studied is MBF [ PA [
DAP not only over Pt–CD [23] but over Pt–QN, CN, QD
catalysts too and the order of their ee values is MBF
points to differences in one or more steps of the mechanism
of the hydrogenation of these compounds. From this point
of view MBF has an intermediate behaviour.
*
PA [ DAP. (ii) The order of the rates of the racemic
Table 2 gives a comparison of the hydrogenation data of
the individual substrates and their binary mixtures. These
data allow some general conclusions to be drawn (the order
of the data listed in Tables 1 and 2 was determined
according to C [ C ): (i) in the case of hydrogenations
hydrogenations due to strongly adsorbing phenyl group is
MBF [ DAP [ PA [23]. (iii) The hydrogenation rate and
the ee depend on the structure of the cinchona used: in
accordance with measurements in batch reactor [24, 43] the
most favorable modifier in the Orito reaction is CD. (iv)
The order of conversions (C) and that of ee values in MBF
hydrogenation are: C: CD * QN [ CN [ QD, ee: CD
S1
S2
proceeding at relatively high rates (MBF), CS1m/CS2m
[ CS1i/CS2i, independently of cinchonas, whereas in the
case of relatively slower hydrogenations (PA ? DAP) this
ratio is nearly identical, which is in agreement with the
higher adsorptivity and/or reactivity of the S1: cinchona
1:1 complex as compared to S2; the same is suggested by
the CS1i/m and the CS2i/m ratios; (ii) attainable ee values are:
eehigh (76–92 %) over Pt–CD catalyst in hydrogenations of
all three substrates and over Pt–QN catalyst in the hydro-
genation of PA; eemed (40–70 %) over Pt–CN catalyst in
hydrogenations of all three substrates and over Pt–QN
catalyst in the hydrogenation of MBF; and, finally, eelow
(5–24 %) over Pt–QD catalyst in hydrogenations of all
three substrates and especially DAP; (iii) there were no
differences among the ratios of enantioselectivities.
[
CN [ QN [ QD; the orders for PA hydrogenation are:
C: CD * QN [ CN [ QD, ee: CD [ QN [ CN [ QD;
the orders for DAP hydrogenation are: C: CD [
CN [ QN [ QD, ee: CD [ CN [ QN * QD. These
orders indicate that the optimal parameters of the hydro-
genations of activated ketones with different structures are
different. (v) As regards the magnitudes of conversions and
ee values, in accordance with batch measurements [24] in
0
6
the case of C -OMe cinchonas (QN, QD) the values are
generally lower than in the case of cinchonas lacking the
0
6
C -OMe group (CD, CN); this phenomenon that calls
attention to the important role of two-point H-bonding
interactions in the cinchona:substrate 1:1 complex [44–47].
(
vi) In agreement with the rule recognized for ethyl pyru-
vate, the configuration of the resulting alcohols is R in the
4 Conclusions
8
presence of CD and QN (C (S), C (R)), and S in the
9
8
9
presence of CN and QD (C (R), C (S)) (see Scheme 1).
vii) As compared with previous investigations [23]
experimental evidence was provided that not only over
Using CFBR method in the enantioselective hydrogenation
attention is called to the following: the magnitude of
conversions and enantioselectivities obtained under
(
123

8
94
G. Sz }o ll }o si et al.
´
nyi Sz, F u¨ l o¨ p F, Bart o´ k M (2008) J Catal
identical experimental conditions depends on the structure
of the cinchona alkaloid present and that of the substrate to
be hydrogenated. The slow rate of the PA hydrogenation,
which is significantly different from the MBF hydrogena-
tion, together with the outstandingly high ee may indicate
differences in some steps of the multistep reaction mech-
anism. The slow hydrogenation rate of PA and DAP may
presumably be related to their adsorption mode and to the
desorption of the product. This phenomenon—slow reac-
tion rate and high ee—unusual in the Orito reaction calls
for further studies (see in Ref. [30], Fig. 8). As regards the
ee values, in the case of all three substrates outstandingly
high, medium and low ee values were also obtained. The
lowest ee values mainly occured with the use of Pt–QD
catalyst. The highest ee values could be attained in the
presence of Pt–CD catalyst.
14. Sz }o ll }o si Gy, Csere
2
60:245
1
5. Sz o¨ ll }o si Gy, Cser e´ nyi Sz, Bal a´ zsik K, F u¨ l o¨ p F, Bart o´ k M (2009)
J Mol Catal A Chem 305:155
16. Meier DM, Ferri D, Mallat T, Baiker A (2007) J Catal 248:68
oll }o si Gy, Cser e´ nyi Sz, Bucsi I, Bart o´ k T, F u¨ l o¨ p F, Bart o´ k M
17. Sz
}
2010) Appl Catal A Gen 382:263
(
8. Baiker A (2005) Catal Today 100:159
9. Blaser HU, Studer M (2007) Acc Chem Res 40:1348
1
1
20. Kieboom AP, van Bekkum H (1972) J Catal 25:342
L, Ru zˇ i cˇ ka V (1981) Adv Catal 30:30
2. Bal a´ zsik K, Sz }o ri K, Sz }o ll }o si Gy, Bart o´ k M (2011) Chem
Commun 47:1551
3. Sz }o ll }o si Gy, Makra Zs, F u¨ l o¨ p F, Bart o´ k M (2011) Catal Lett
141:1616
zsik K, Bucsi I, Cser e´ nyi Sz, Sz }o ll }o si Gy, Bart o´ k M (2008)
J Mol Catal A: Chem 285:84
5. Bart o´ k M, Sutyinszki M, Felf o¨ ldi K (2003) J Catal 220:207
6. Bart o´ k M, Sutyinszki M, Bal a´ zsik K, Sz }o ll }o si Gy (2005) Catal
Lett 100:161
ˇ
21. Cerveny
´
2
2
24. Bala
´
2
2
These experimental observations showed identical ten-
dencies as were obtained in batch reactors. However, the
interpretation, of the differences between the results
obtained in batch and in continuous flow reactors neces-
sitates further studies and a more profound knowledge of
reaction kinetics.
27. Studer M, Burkhardt S, Blaser HU (1999) Chem Commun 1727
2
2
8. Bal a´ zsik K, Bart o´ k M (2004) J Catal 224:463
9. Felf o¨ ldi K, Bal a´ zsik K, Bart o´ k M (2003) J Mol Catal A: Chem
2
02:163
30. Studer M, Blaser HU, Exner C (2003) Adv Synth Catal 345:45
31. Ferri D, B u¨ rgi T, Baiker A (2001) Chem Commun 13:1172
3
2. Ferri D, B u¨ rgi T (2001) J Am Chem Soc 123:12074
33. Somorjai GA, van Hove MA (1989) Prog Surf Sci 30:201
3
4. T o¨ r o¨ k B, Felf o¨ ldi K, Szakonyi G, Bart o´ k M (1997) Ultrason
Sonochem 4:301
Acknowledgments Financial support by the Hungarian National
Science Foundation (OTKA Grant K 72065) is highly appreciated.
The study was supported by the J a´ nos Bolyai Research Scholarship of
the Hungarian Academy of Sciences (Gy. Sz }o ll }o si).
3
3
3
5. T o¨ r o¨ k B, Bal a´ zsik K, T o¨ r o¨ k M, Felf o¨ ldi K, Bart o´ k M (2002)
Catal Lett 81:55
6. Mallat T, Frauchinger S, Kooyman PJ, Sch u¨ rch M, Baiker A
(
1999) Catal Lett 63:121
7. Ma Z, Kubota J, Zaera F (2003) J Catal 219:404
References
38. Zaera F (2008) J Phys Chem C 112:16196
3
4
9. Hess R, Krumeich F, Mallat T, Baiker A (2004) Catal Lett 92:141
0. Baddeley CJ, Jones TE, Trant AG, Wilson KE (2011) Top Catal
1
2
3
4
. Izumi Y (1971) Angew Chem Int Ed 10:871
. Osawa T, Harada T, Takayasu O (2006) Curr Org Chem 10:1513
. Orito Y, Imai S, Niwa S (1979) J Chem Soc Jpn 1118
. Murzin DY, Maki-Arvela P, Toukoniitty E, Salmi T (2005) Catal
Rev Sci Eng 47:175
. Mallat T, Orglmeister E, Baiker A (2007) Chem Rev 107:4863
. T a´ las E, Margitfalvi JL (2009) Chirality 22:3
. Bart o´ k M (2010) Chem Rev 110:1663
5
4:1348
1. LeBlanc RJ, Chu W, Williams CT (2004) J Mol Catal A: Chem
12:277
4
4
2
2. Bakos I, Szab o´ S, Bart o´ k M, K a´ lm a´ n E (2002) J Electroanal
Chem 532:113
5
6
7
8
9
4
4
3. Bart o´ k M (2006) Curr Org Chem 10:1533
4. Exner C, Pfaltz A, Studer M, Blaser HU (2003) Adv Synth Catal
3
45:1253
. K u¨ nzle N, Hess R, Mallat T, Baiker A (1999) J Catal 186:239
. Li X, Li C (2001) Catal Lett 77:251
4
5. Lavoie S, Laliberte MA, Temprano I, McBreen PH (2006) J Am
Chem Soc 128:7588
1
1
0. Toukoniitty E, Murzin DYu (2004) Catal Lett 93:171
1. Toukoniitty E, W a¨ rn a˚ J, Murzin DYu, Salmi T (2010) Chem Eng
Sci 65:1076
2. Meier DM, Mallat T, Ferri D, Baiker A (2006) J Catal 244:260
3. Gao F, Chen L, Garland M (2006) J Catal 238:402
4
4
6. Martinek TA, Varga T, F u¨ l o¨ p F, Bart o´ k M (2007) J Catal 246:266
7. Martinek TA, Varga T, Bal a´ zsik K, Sz o¨ ll }o si Gy, F u¨ l o¨ p F,
Bart o´ k M (2008) J Catal 255:296
1
1
1
23