Regioselective hydrogenation of 1,2-indanedione over heterogeneous Pd and Pt catalysts

Article abstract of DOI:10.1007/s10562-012-0951-9

Regioselective hydrogenation of 1,2-indanedione yielding rac-2-hydroxy-1-indanone was investigated using heterogeneous Pt and Pd as catalysts. Five consecutive experiments were carried out for studying the performance of Pd/Al₂O₃. Pr

Full text of DOI:10.1007/s10562-012-0951-9

Catal Lett (2013) 143:142–149
DOI 10.1007/s10562-012-0951-9
Regioselective Hydrogenation of 1,2-Indanedione Over
Heterogeneous Pd and Pt Catalysts
•
Otto Langvik Paivi Maki-Arvela Atte Aho
•
•
˚
Tiina Saloranta Dmitry Yu Murzin
¨
¨
•
•
Reko Leino
Received: 30 October 2012 / Accepted: 5 December 2012 / Published online: 20 December 2012
Ó Springer Science+Business Media New York 2012
Abstract Regioselective hydrogenation of 1,2-indanedi-
one yielding rac-2-hydroxy-1-indanone was investigated
using heterogeneous Pt and Pd as catalysts. Five consecu-
tive experiments were carried out for studying the perfor-
mance of Pd/Al2O3. Practical operation under atmospheric
pressure of hydrogen at low temperature (40 °C) for
120 min gave the desired product in [99 % regioselec-
tivity, 84 % conversion and 77 % yield, according to GC,
using 2 mol% Pd/Al2O3 as the catalyst.
potential recycling and ease of handling of the catalysts and
generally more facile work-up of the reactions [1]. Chiral
small organic molecules, such as (R)-2-hydroxy-1-inda-
none [(R)-2] and (1S,2R)-1-amino-2-indanol [(S,R)-3]
(Fig. 1), are important building blocks for synthesis of
biologically active compounds [2–8]. Both enantiomers of
cis-1-amino-2-indanol also find application in asymmetric
catalysis and as chiral auxiliaries and as chiral resolving
agents [9–16].
Recently, we have reported the synthesis of (R)-1-oxo-
indan-2-yl butanoate, the butyl ester of (R)-2, by chemo-
enzymatic dynamic kinetic resolution (DKR) utilizing
heterogeneous metal catalyst for racemization together
with an immobilized enzyme catalyst for resolution, thus
providing a simple and practical route towards this class of
compounds [17]. As shown earlier by others, (R)-2 can
easily be transformed into the corresponding aminoindanol,
(S,R)-3 [8]. In the present work, the primary aim was to
investigate the possibilities for utilizing heterogeneous
catalysis for preparation of rac-2-hydroxy-1-indanone
[rac-(2)] by developing regioselective hydrogenation of
1,2-indanedione (1).
Keywords 1,2-Indanedione Á 2-Hydroxy-1-indanone Á
Regioselectivity Á Heterogeneous catalysis Á Hydrogenation
1 Introduction
The increasing demand for enantiomerically pure small
molecule building blocks in pharmaceutical and fine
chemical applications promotes the search for new, effi-
cient and environmentally benign synthetic methods for
their preparation. From the industrial point of view, het-
erogeneously catalyzed processes are preferred due to
In a regioselective chemical transformation, one func-
tional group of the starting material reacts in a controlled
fashion leaving other similar functional groups at other
positions intact. Such differences in reaction rates between
similar chemical functionalities may result from the
chemical and structural nature of the substrate itself, or be
controlled by structure of the catalyst used for the desired
transformation [18–21].
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-012-0951-9) contains supplementary
material, which is available to authorized users.
˚
O. Langvik Á T. Saloranta Á R. Leino (&)
˚
Laboratory of Organic Chemistry, Abo Akademi University,
˚
20500 Abo, Finland
e-mail: reko.leino@abo.fi
Transition metal catalyzed hydrogenation of ketones to
secondary alcohols, typically by Pd or Pt catalysts, is a
widely employed synthetic transformation. Under optimal
reaction conditions, vicinal diketones may undergo regio-
selective hydrogenation of one of the keto groups only,
¨
P. Maki-Arvela Á A. Aho Á D. Y. Murzin (&)
Laboratory of Industrial Chemistry and Reaction Engineering,
˚
Process Chemistry Centre, Abo Akademi University,
˚
20500 Abo, Finland
e-mail: dmurzin@abo.fi
123

Regioselective Hydrogenation of 1,2-Indanedione
143
2 Experimental
2.1 Synthesis of the Starting Material and Reference
Compounds
Fig. 1 The structures of (R)-2 and (S,R)-3
The starting material 1, rac-2, and rac-1-hydroxy-2-inda-
none were prepared according to literature procedures with
1H and 13C NMR spectroscopic data identical to those
reported previously [28–32].
thereby providing access to synthetically valuable a-hydroxy
ketones. In earlier work, we have studied the asymmetric
and regioselective hydrogenation of the prochiral diketone
1 over cinchona alkaloid modified heterogeneous Pt cata-
lysts to yield (R)-2 [22]. In contrast to enantioselective
hydrogenation of the structurally related diketone, 1-phe-
nyl-1,2-propanedione, providing up to 70 % enantiomeric
excess in moderate regioselectivity when hydrogenated
using cinchona alkaloid modified Pt catalysts [23–25], the
enantiomeric excess obtained in the hydrogenation of 1 was
only moderate at its best and insufficient for a direct route
towards enantiomerically pure (R)-2. Remarkably, how-
ever, the regioselectivity towards 2-hydroxy-1-indanone
was nearly complete [22].
2.2 Catalytic Experiments
The hydrogenation experiments were conducted in a five-
necked 100 mL round-bottom flask equipped with a
mechanical stirrer (gas tight adaptor), gas inlet (7 lm gas
disperser merged in the solvent), in situ thermocouple
recording the temperature, funnel (with degassing capa-
bility), rubber septa for sampling and condenser further
connected to an oil bubbler for gas outlet. Commercial
catalysts used in the hydrogenation experiments were: Pd/
Al2O3 (Aldrich 205710; 5 wt% Pd); Pt/Al2O3 (Johnson–
Matthey type 123; 5 wt% Pt) and Pt/Al2O3 (Johnson–
Matthey type 5R94; 5 wt% Pt). The hydrogenation
reactions were performed using hydrogen gas (Linde Gas–
AGA, 99.999 %) under atmospheric pressure at 40 °C. The
catalysts were pretreated under H2 flow for 2 h at elevated
temperatures (250 °C for Pd and 400 °C for Pt) in order to
ensure that all active metal is in metallic form (oxidation
state zero).
Notably, as described in our earlier work, the hetero-
geneously catalyzed chemoenzymatic DKR of rac-2 pro-
vides access to the corresponding butyl ester in high
enantiomeric excess [17]. In the present work, we have
investigated the heterogeneously catalyzed hydrogenation
of 1 (Scheme 1) over both Pt and Pd catalysts under mild
reaction conditions, under atmospheric pressure of hydro-
gen and low temperatures. The regioselective hydrogena-
tion of 1 was studied earlier only with Pt as the catalyst
[22]. The aim of the present work was, therefore, to
develop a practical method for synthesis of rac-2 by uti-
lizing an effective Pd or Pt based catalyst and a simple
reaction protocol. The regioselective hydrogenation of 1,
yielding rac-2, could then ideally be combined with the
earlier described DKR into a one-pot reaction sequence to
produce an enantiomerically pure ester of (R)-2. The main
focus of the present paper is thus the regioselectivity.
Important factors in the operation and recycling of the
catalyst are, however, also its activity and stability [26, 27].
Additionally, origin of the observed catalyst deactivation is
briefly discussed herein.
In a typical experiment, 1,2-indanedione (1.2 mmol,
175 mg) was dissolved in ethyl acetate (60 mL) and
transferred to a funnel directly connected to the hydroge-
nation vessel. The reactions were carried out with dodecane
as an internal standard (0.3 mmol, 68 lL). Deoxygenation
of the solution was carried out in the funnel shortly before
reaction by bubbling with H2 (15 min). The reaction was
started by introducing the deoxygenated solution into the
reaction vessel containing the activated catalyst. The
hydrogen flow rate during the reaction was 25–35 mL/min.
Efficient stirring (500 rpm), small catalyst particle size
(\63 lm) and metal loadings between 1 and 3 mol%
active metal were used for obtaining experimental data in
the kinetic regime. For isolation of the product, the catalyst
was removed by filtration through Celite. For collecting
and recycling the catalyst material, the crude separation
and washing were performed by removing the liquid phase
from the top of the reaction vessel. The small-sized catalyst
particles were allowed to sediment overnight in a tube-
shaped vessel after which the liquid was removed by using
a syringe and needle. The catalyst particles could thereafter
be transferred back to the reactor. Direct filtration of the
catalyst was found unfeasible due to the fine powder-like
Scheme 1 Regioselective hydrogenation of 1,2-indanedione (1) to
rac-2-hydroxy-1-indanone (rac-2)
123

˚
O. Langvik et al.
144
character of the catalyst material sticking to all filter
materials investigated.
scanning system equipped with a secondary and back-
scattered electron detector.
2.3 Analysis
3 Results and Discussion
Samples (0.15 mL) from the reactor were taken periodi-
cally through a gas tight septum, filtered using a 0.2 lm
syringe filter and diluted with three parts of the same sol-
vent after which 1 lL of the solution was injected to the
gas chromatograph. The product distribution was moni-
tored by GC and GC/MS. The GC apparatus used was
Agilent Technologies 6850 GC equipped with a Varian
CP-7502 column (25.0 m 9 250 lm 9 0.25 lm), He as a
carrier gas, FID detector and the following temperature
3.1 Hydrogenation of 1,2-Indanedione
All experiments were preceded by in situ pretreatment of
the catalyst at elevated temperatures (250 °C for Pd;
400 °C for Pt) under hydrogen atmosphere (1 atm). Three
different catalyst concentrations, 1.0, 2.0 and 3.0 mol%,
were used for determining the initial reaction rates. The
samples were withdrawn in the beginning of the reaction
when the concentration of the starting material decreased
linearly (supporting information, Fig. S1). When the cal-
culated initial rates were plotted against the catalyst con-
centration, a linear correlation was obtained confirming
that the reaction proceeds without external (gas/liquid)
mass transfer limitations (supporting information, Fig. S2).
Methyl tert-butyl ether (MTBE) was initially selected as
a solvent for the hydrogenation experiments being suc-
cessfully used in our earlier published DKR of rac-2 [17].
However, in the hydrogenation experiments, when 1 was
used as the starting material, MTBE was not sufficiently
efficient for reliable and practical operation. By switching
the solvent to ethyl acetate (EA) better reproducibility and
more reliable results were obtained.
program: injector 230 °C, detector 280 °C, oven Tinitial
=
130 °C (0 min), rate 2.2 °/min, Tfinal = 185 °C (10 min).
The GC/MS apparatus used was Agilent Technologies
7890 A GC equipped with 5975 C MS detector (EI),
HP-5MS column (30 m 9 250 lm 9 0.25 lm), He as a
carrier gas and the following temperature program: injector
250 °C, oven Tinitial = 90 °C (0 min), rate 7 °C/min,
Tfinal = 280 °C, hold 2 min. The NMR spectra of the
isolated compounds were recorded on a Bruker Avance
600 MHz NMR spectrometer equipped with a BBI-5 mm-
Zgrad–ATM probe at 25 °C operating at 600.13 MHz for
1H and 150.92 MHz for 13C.
The metal dispersion was determined by applying CO
pulse chemisorption method using Micromeritics Auto-
Chem 2900 apparatus. Pd and Pt dispersions were calcu-
lated assuming an adsorption stoichiometry of 1/1 for both
CO/Pd and CO/Pt, respectively [33, 34]. The specific sur-
face areas of the fresh and the used Pd/Al2O3 catalysts were
measured by nitrogen physisorption using an automatic
physisorption apparatus (Sorptomatic 1900, Carlo Erba
Instruments). BET method was used for calculations of
the surface areas. The catalysts were degassed prior to the
surface area measurements in vacuum at 150 °C. The
inductively coupled plasma optical emission spectrometry
(ICP–OES; PerkinElmer, Optima 5300 DV) was performed
at 340.458 nm. For the ICP–OES analysis, the solid cata-
lyst was removed by filtration through a small pad of Celite
and the remaining solution was concentrated to 1/10 of its
original volume. Of the obtained sample, 0.5 g was trans-
ferred to a Teflon bomb and 6 mL of HNO3 (65 %) and
1 mL of H2O2 (30 %) were added. Next, the sample was
digested in a microwave oven (Anton Paar, Multiwave
3000) and diluted to 100 mL volume with deionized water
(18 MX) prior to analysis. The thermogravimetric analyses
were performed using a DSC–TGA (TA Instruments, Q
Series instrument) and the analyses were performed under
nitrogen atmosphere using a heating rate of 5 °C/min.
SEM–EDXA analysis was performed by using a LEO 1530
The performance of three different catalysts, Pt/Al2O3
(123), Pt/Al2O3 (5R94) and Pd/Al2O3 was investigated in
the hydrogenation of 1. With the Pd and Pt catalysts
(2 mol%, 51.3 mg Pd/Al2O3 or 93.6 mg Pt/Al2O3), 1 was
converted to rac-2 in high selectivity (99 %) at up to 50 %
conversion. While with increasing conversion the selec-
tivity decreased, acceptable selectivities (92–94 %) were
obtained with Pd/Al2O3 at 75–80 % conversion (Fig. 2).
For chemoselective hydrogenations of carbonyl com-
pounds, heterogeneous Pt catalysts have been more fre-
quently used compared to Pd [35]. Heterogeneous Pd
systems are commonly employed catalysts for hydrogena-
tion of C–C double bonds whereas earlier examples of
their use in selective carbonyl reductions are less frequent
[35–37].
The metal dispersions and the corresponding average
metal particle sizes of the catalysts and the BET specific
surface areas are shown in Table 1. The initial turn over
frequency (TOF) values, calculated based on the 10 min
sample, were similar for both Pt/Al2O3 and Pd/Al2O3 cat-
alysts (Table 1). Pd exhibited slightly higher metal dis-
persion compared with the two Pt catalysts but the TOF
values did not depend on the metal dispersion within the
studied range. Overall, the variation of metal dispersions
123

Regioselective Hydrogenation of 1,2-Indanedione
145
Fig. 2 Kinetics of the
hydrogenation of 1 using Pt/
Al2O3 type 123 (black square),
Pt/Al2O3 type 5R94 (black
triangle), Pd/Al2O3 (black
circle) displayed as a function
of a concentration of 1, and
b concentration of rac-2
Table 1 Metal dispersion, particle size, BET specific area, turn over frequencies and final conversions in the hydrogenation of 1 with the studied
catalysts under atmospheric pressure of H2 and EA as the solvent
Entry
Catalysta
Metal dispersion
(%)
Metal particle
size (nm)
BETb
(m2/g)
TOF (s-1
0–10 min
)
TOF (s-1
10–30 min
)
Final conversion
at 120 min (%)
1
2
3
Pd/Al2O3
22
17
13
5.1
6.5
8.5
174
131
n.d.
0.21
0.21
0.18
0.018
0.043
0.037
75
68
57
Pt/Al2O3 (type94)
Pt/Al2O3 (type123)
The reported values are based on one representative reaction, [1] = 0.02 mol/L
a
2 mol%
b
Determined for fresh catalysts
was minimal and further conclusions on the TOF depen-
dence on the metal particle size could not be drawn.
catalysts were analyzed by thermogravimetric analysis
(TGA) and Fourier transformed infrared spectroscopy
(FTIR). The TGA results showed some variations between
the fresh and spent catalysts (supporting information, Figs.
S3, S4). The fresh material had lost 6 wt% at 150 °C.
Thereafter, the decrease gradually stabilized, indicating
that the catalyst contains some moisture. The spent catalyst
exhibited a linear decrease of mass without any clear
degradation or decomposition temperatures. Similar TGA
results have been observed for the same type of materials in
the absence of catalyst deactivation [38]. The mass loss of
spent catalyst was minor (\5 % at 500 °C). The FTIR
results showed only small deviations between the fresh and
spent catalysts (supporting information, Figs. S5, S6) not
clarifying the observed catalyst deactivation. Deactivation
due to metal leaching was likewise ruled out as discussed
in Sect. 3.1.3.
3.1.1 Deactivation of the Catalysts
The catalysts studied were found to be very selective and
active during the initial stages of the reaction. After pro-
longed reaction time, the reaction rate declined. Retarda-
tion of the reaction rate was evident from analysis of the
shapes of the reaction concentration profiles (Fig. 3),
decline of the average TOF calculated for the reaction time
0–10 min and 10–30 min, and the final conversion at
120 min (Table 1). The observed inhibition of the reaction
is assumed to be a consequence of catalyst deactivation.
Performances of the catalysts studied were similar, indi-
cating that the deactivation is independent on the active
metal. Potential origins of the deactivation may include
coking, metal leaching or strong poisoning by either
impurities or reaction products [27].
For further analysis, the elemental composition of the
spent Pd catalyst was investigated with SEM–EDXA. The
spent catalyst surface was found to contain 0.44 wt% sulfur
and 0.16 wt% sodium (supporting information, Table S1).
In case of deactivation due to coking, the BET specific
surface area of the catalyst would typically decline sig-
nificantly during the catalytic reaction. Surprisingly, results
of the BET area measurements showed the opposite
behavior even after repeated experiments, verifying their
reproducibility. In two parallel reactions with Pd/Al2O3
catalysts, the observed specific surface areas prior to and
after the reaction were 174 versus 226 m2/g and 169 versus
231 m2/g, respectively, showing considerable increase
during the reaction. For further studying this behavior, the
The Pd loading of the catalyst was 5.0 wt% (50 mg/gcat
)
corresponding to the molar amount 0.470 mmol/gcat. Tak-
ing the dispersion (22 %) into account, the molar amount
of Pd at the surface, accessible for reaction, was
0.103 mmol/gcat. If the sulfur, 0.44 wt% (4.4 mg/gcat
)
according to SEM–EDXA analysis, would be fully dis-
persed, the corresponding molar amount at the surface of
the catalyst would be 0.137 mmol/gcat, which is in excess
123

˚
O. Langvik et al.
146
Fig. 3 a Concentration profile of 1 (white circle), rac-2 (white
square) and indanediols (white triangle) during the hydrogenation
reaction of 1 (1.2 mol) using 2 mol% Pd in EA (60 mL), b conversion
of 1 versus selectivity towards rac-2 in hydrogenation reaction of 1
(1.2 mol) in EA (60 mL) using 2 mol% Pt-123/Al2O3 (black
square),Pt-94/Al2O3 (black triangle) and Pd/Al2O3 (black circle)
compared to the Pd amount. It should, however, be noted
that sulfur may potentially adsorb not only on the Pd sur-
face but also on the support. Therefore, the slow reaction
rate observed at prolonged reaction times could, at least in
part be attributed to sulfur deposited on the catalyst sur-
face. Such deposition and poisoning could principally
originate from the gas, solvent, catalyst or substrate of
which the gas and the solvent can be ruled out based on the
suppliers’ quality assurance. Thus, the only, although
unlikely, source of sulfur contamination is the substrate,
1,2-indanedione. Therefore, some further attempts for
elimination of the possible sulfur contamination from 1
were made. Initially, 1 was dissolved in acetone and the
possible sulfur contamination removed by use of active
carbon followed by recrystallization of 1 from acetone.
This procedure did not, however, improve the results of the
hydrogenation reaction. Next, the synthetic procedure for
preparation of 1 was modified by replacing the concen-
trated sulfuric acid used for hydrolysis of the 2-oxime-
1-indanone precursor to concentrated HCl. The potential
hazard in the use of HCl is the possible formation of a toxic
and carcinogenic by-product, bis (chloromethyl) ether,
discussed earlier by Gupta and Marathe [29]. Nevertheless,
the hydrogenation of 1, synthesized without the use of
sulfuric acid, exhibited an apparent slightly increased
reaction rate and conversion compared to the earlier
experiments using 1 prepared by the literature method. The
average TOF value during 0-10 min increased slightly
from 0.21 to 0.22 s-1 and the conversion at 120 min from
75–80 to 84 %. In addition, the spent Pd/Al2O3 catalyst
was analyzed by SEM–EXDA after the hydrogenation
verifying that no sulfur or chlorine was present on the
catalyst surface after the hydrogenation (supporting infor-
mation, Fig. S9; Table S2) when 1 was prepared using HCl.
These results suggest that the Pd catalyst in the hydroge-
nation of 1 could potentially be poisoned by sulfur origi-
nating from the concentrated H2SO4 used in the synthetic
preparation of 1. If the probable sulfur contamination
originating from the H2SO4 would sustain its acidity it
could cause some leaching of Al from the Al2O3 structure
creating additional porosity. This then could in principle
account for the increase in the specific surface area of the
Pd/Al2O3 catalyst analyzed before and after the hydroge-
nation reactions.
3.1.2 Selectivity
The reactions over the Pd/Al2O3 catalyst gave after
120 min slightly higher conversions with selectivities
similar to those observed for the two Pt catalysts (Table 2).
The observed conversion of 1 over the Pt catalysts studied
correlated with the metal dispersions of the catalyst
materials. The Pt/Al2O3 (type94) catalyst also exhibited
slightly higher values of metal dispersion and conversion.
Due to the better overall performance and lower pretreat-
ment temperature required, the Pd/Al2O3 catalyst was then
selected for further studies.
During the first 30 min of the reaction, the formation
rate of indanediols was much lower (0.57 lmol/min)
compared to that of rac-2 (24 lmol/min) (Fig. 3). After
120 min, the conversion of 1 exceeded 80 %, the concen-
tration of rac-2 started to decrease and the concentration of
the isomeric indanediols increased from 1 mmol/L (2 h) to
10 mmol/L (18 h). The slow rate of formation of the
indanediols together with the very high selectivity towards
rac-2 during the initial stages, followed by the decline of
rac-2 concentration together with the formation of diols,
shows that the indanediols are formed from rac-2 only. In
order to maximize the yield of rac-2 and to minimize the
formation of indanediols, the reaction time of 120 min was
found optimal with 2 mol% Pd corresponding to 84 %
conversion of 1 .
Only negligible amounts of the regioisomeric byproduct
rac-1-hydroxy-2-indanone were detected in the hydroge-
nation reactions. Similar high regioisomeric selectivity
towards rac-2 has been reported earlier by Chiang et al.
123

Regioselective Hydrogenation of 1,2-Indanedione
147
regioselectivity towards ketone moiety adjacent to the
aromatic ring has been explained by the interactions
between the substrate and the metal surface. The preferred
adsorption mode for 1-phenyl-1,2-propanedione has both
the phenyl ring and the adjacent carbonyl group oriented
parallel to the metal surface [40]. Furthermore, it has been
shown that adsorption of the two carbonyl groups in cis
orientation parallel to the active metal surface is unfavor-
able. Thus, while structurally related, the two substrates
1-phenyl-1,2-propanedione and 1,2-indanedione appear to
exhibit different adsorption behavior on the catalyst surface
thus resulting in opposite regioselectivities as also
observed experimentally.
Table 2 Conversion of 1 and selectivity towards rac-2 using Pd and
Pt catalysts
Entry Catalysta
Pretreatment
temperature
under H2 flow
(°C)
Conversion
of 1,2-
indanedione
(%)b
Selectivity
for rac-2
(%)b
1
2
Pd/Al2O3
250
400
84
68
92
93
Pt/Al2O3
(type94)
3
Pt/Al2O3
(type123)
400
57 (61c)
96
The reported values are based on one representative reaction
a
2 mol%
b
At 120 min determined by GC
c
3.1.3 Catalyst Recycling and Product Isolation
Verified by NMR analysis
In order to verify the performance and practical applica-
bility of the catalyst, the same catalyst material was recy-
cled and used in five consecutive experiments. Similar to
the earlier experiments, the Pd/Al2O3 catalyst was acti-
vated prior to each reaction under hydrogen flow at 250 °C.
The progress of all individual reactions was monitored by
sampling during the reactions (Fig. 4), resulting in a slight
decrease in the amount of catalyst (1–1.5 %) in each
reaction. Such marginal decrease in the substrate to catalyst
ratio is, however, unlikely to be related to the observed
decrease in the initial reaction rate which, as discussed
earlier, is more likely due to catalyst poisoning influencing
also the conversions of the consecutive experiments
(Fig. 4).
[32]. In their study, the kinetics and the mechanism of the
acid catalyzed hydrolysis of the corresponding diazo
compounds 1-diazo-2-indanone and 2-diazo-1-indanone
were investigated (Scheme 2).
In the earlier study, the hydrolysis of 2-diazo-1-inda-
none, yielding rac-2, was found to be considerably faster
than the hydrolysis of the corresponding regioisomer. The
difference in the reactivity of the two diazo compounds
was suggested to be a result of electron delocalization to
the aromatic moiety when the diazo group is adjacent to an
aromatic ring, decreasing the basic character of the diazo
carbon in position 1 [32]. Similarly, in the present work,
the high regioselectivity in the hydrogenation of 1 yielding
rac-2 likely results from the large reactivity difference
between the two keto groups. The hypothesis is also sup-
ported by the similar selectivities of both Pd and Pt cata-
lysts towards rac-2 in the hydrogenation of 1. The adjacent
aromatic ring remarkably decreases the reactivity of the
carbonyl group in position 1.
Generally, a decrease in the catalytic activity due to
sulfur poisoning is considered irreversible [41]. It is
known, however, that sulfur contamination originating
Notably, the observed regioselectivity in the hydroge-
nation of 1,2-indanedione [22] is reversed as compared to
the regioselectivity in the hydrogenation of the structur-
ally more flexible analogue, 1-phenyl-1,2-propanedione
[23–25, 39, 40]. For 1-phenyl-1,2-propanedione, the
Fig. 4 Conversion (%) versus time (min) in the recycling of Pd/
Al2O3 catalyst during hydrogenation of 1 to rac-2: black diamond
first, black square second, black triangle third, 9 fourth and white
circle fifth experiments
Scheme 2 Acid catalyzed hydrolysis of the regioisomeric diazoinda-
nones [32]
123

˚
O. Langvik et al.
148
Scheme 3 i Hydrogenation of 1
yielding rac-2, ii hydrogenation
of 1 combined with in situ
derivatization to 2-acetoxy-1-
indanone
from different sources may exhibit two different types of
sulfur poisoning, irreversible and labile [41]. A catalyst
deactivated by labile type of sulfur contamination can in
principle be regenerated by eliminating the source of sulfur
and by utilizing reductive conditions at elevated tempera-
tures [42]. When 1 is hydrogenated using 2 mol%
Pd/Al2O3, the initial rate (0–4 min) for the first reaction
was 0.132 mmol/min and for the fifth reaction
0.066 mmol/min. While the initial rate declines in the
consecutive experiments, regeneration of the Pd/Al2O3
catalyst under hydrogen flow at 250 °C appears to partially
retain the catalytic activity (Fig. 4).
regioselective hydrogenation of the carbonyl group in
position C-2. While substantial differences between the Pd
and Pt catalysts investigated were not observed, Pd/Al2O3
was found to be more efficient for practical use. Hydro-
genation of 1 (0.02 M) in EA under atmospheric pressure
of H2 produced, according to GC-analysis, rac-2 in 77 %
yield using 120 min reaction time and 2 mol% of Pd/
Al2O3. While the reaction proceeds with high selectivity
and reasonable isolated yield, it suffers from catalyst
deactivation at prolonged reaction times. The removal of
sulfur contamination responsible for the inhibition was
investigated and the yield of hydrogenation could be
slightly improved by replacing the H2SO4 used in the
synthetic preparation of 1 with HCl. In future work we aim
to utilize the hydrogenation reaction as a starting point for
development of a cascade type, one-pot reaction sequence
towards chiral hydroxy ketones in the presence of a stereo
differentiating enzyme.
In order to verify that the reaction fully proceeds under
heterogeneously catalyzed conditions without leaching of
Pd to the liquid phase, ICP–OES analysis was used.
According to the analysis, the amount of dissolved Pd is
below the detection limit (2 ppm) thus indicating that the
actual concentration of dissolved metal is likely to be even
lower and does not influence the overall catalytic activity.
Theprimaryobjectiveof thepresent workwasto developa
practical process for obtaining rac-2 from 1 in high conver-
sion and selectivity in sufficiently high isolated yield. Based
on the conversion and selectivity, the expected yield should
be in the 70–77 % range. After filtration of the catalyst,
removal of the solvent and chromatographic purification, the
isolated yield of rac-2 remained at 45 %. Changes in eluent
systems or column material in the chromatographic purifi-
cation did not improve the yield. In order to improve the
isolated yield, an in situ derivatization of the hydroxyl group
in rac-1 to the corresponding ester was attempted
(Scheme 3). Disappointingly, only marginal improvement of
the isolated yield to 48 % was obtained. Such high losses of
isolated yield are evidently due to the small scale of operation
investigated here. Thus, future scale-up of the hydrogenation
reaction will likely decrease the mass losses arising from
operational techniques with small quantities and conse-
quently improve the isolated yield.
Acknowledgments The authors thank the Graduate School of
Materials Research, Suomen Kemian Seura, Magnus Ehrnrooths
˚
stiftelse and Seniorernas rad vid Abo Akademis Studentkar for
˚
financial support. Linus Silvander (Abo Akademi University-Process
˚
˚
Chemistry Center) is acknowledged for SEM-EDX analyses.
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