Chemoselective transfer hydrogenation of α,β-unsaturated carbonyls using palladium immobilized ionic liquid catalyst

Article abstract of DOI:10.1007/s10562-014-1362-x

This work reports a simple and highly efficient protocol for chemoselective transfer hydrogenation of α,β-unsaturated carbonyls using immobilized palladium metal-containing ionic liquid as a versatile heterogeneous catalyst with an excellent conversion and chemoselectivity (up to 100 %). The influence of various reaction parameters such as the effect of hydrogen donor, solvent, temperature, and time were studied. The catalyst was recycled for four consecutive cycles without significant loss in the catalytic activity. The developed protocol is more advantageous due to the use of HCOONH₄ as a hydrogen source, mild reaction conditions, and simple workup procedure and applicable for a wide range of substrates.

Full text of DOI:10.1007/s10562-014-1362-x

Catal Lett (2014) 144:1803–1809
DOI 10.1007/s10562-014-1362-x
Chemoselective Transfer Hydrogenation of a,b-Unsaturated
Carbonyls Using Palladium Immobilized Ionic Liquid Catalyst
•
Nilesh M. Patil Takehiko Sasaki
•
Bhalchandra M. Bhanage
Received: 28 July 2014 / Accepted: 3 September 2014 / Published online: 14 September 2014
Ó Springer Science+Business Media New York 2014
Abstract This work reports a simple and highly efficient
protocol for chemoselective transfer hydrogenation of
a,b-unsaturated carbonyls using immobilized palladium
metal-containing ionic liquid as a versatile heterogeneous
catalyst with an excellent conversion and chemoselectivity
(up to 100 %). The influence of various reaction parame-
ters such as the effect of hydrogen donor, solvent,
temperature, and time were studied. The catalyst was
recycled for four consecutive cycles without significant loss
in the catalytic activity. The developed protocol is more
advantageous due to the use of HCOONH4 as a hydrogen
source, mild reaction conditions, and simple workup
procedure and applicable for a wide range of substrates.
attention due its broad application in pharmaceutical, agro-
chemicals and various valuable materials [1]. The saturated
carbonyl moieties are useful key intermediates for the syn-
thesis of various biologically active compounds such as HIV-I
protease inhibitors, in addition dihydrochalcone is useful in
restraining the development of Molt-4 human leukemic cells
[2, 3]. Selective reduction of the olefinic bond of a,b-unsat-
urated carbonyl compounds without affecting carbonyl group
is one of the significant transformation, since both the olefinic
double bond and carbonyl bonds are thermally susceptible for
reduction [4]. Often the use of flammable hydrogen gas as a
reducing agent was used and additionally it requires sophis-
ticated instrument like high pressure reactors [5].The use of
transfer hydrogenation is more attractive and convenient
alternative method for this conversion avoiding the use of
hydrogen gas and high pressure reactors [6, 7].
Keywords Transfer hydrogenation Á Chemoselective Á
Immobilization Á Palladium Á Heterogeneous catalyst
The chemoselective olefin bond reduction in a,b-unsat-
urated carbonyl was studied using various transition metal
catalystssuch as palladium [8, 9], rhodium [10], iridium [11],
ruthenium [12], and other metal catalysts [13]. Recently,
Zhang et al. reported chemoselective transfer hydrogenation
of a,b-unsaturated carbonyl compounds by using homoge-
nous palladium pincer complexes [14]. In 2012, Kantam and
co-workers explored the use of Pd/Mg-La mixed metal oxide
as a catalyst for selective hydrogenation of a,b-unsaturated
carbonyl compounds using molecular hydrogen [15]. How-
ever, in spite of their potential utility, previous reports
associated with some disadvantages e.g. less chemoselec-
tivity, use of flammable hydrogen gas, use of hazardous
metal hydride and use of expensive metals/ligands in
homogenous system, therefore, difficulties in catalyst prod-
uct separation from the reaction mixture. These restrict their
applications in fine chemical industries. Hence, to overcome
these drawbacks, the exploration of heterogeneous catalytic
system is still highly desirable.
1 Introduction
Recently, chemoselective hydrogenation of the olefinic bond
ofa,b-unsaturatedcarbonylcompoundshas beenpayinggreat
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-014-1362-x) contains supplementary
material, which is available to authorized users.
N. M. Patil Á B. M. Bhanage (&)
Department of Chemistry, Institute of Chemical Technology,
N. Parekh Marg, Matunga, Mumbai 400019, India
e-mail: bm.bhanage@ictmumbai.edu.in
T. Sasaki
Department of Complexity Science and Engineering, Graduate
School of Frontier Sciences, The University of Tokyo,
5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan
123

1804
N. M. Patil et al.
Scheme 1 Chemoselective
transfer hydrogenation of
a,b-unsaturated carbonyls
O
OH
O
ImmPd-IL HCOONH
,
4
+
o
Toluene,
12
h
90 C
,
a
3
a
2
1a
Convesion: 99%
Selectivit: 2a : 3a
99 : 01
Scheme 2 The preparation of
palladium metal-ion-containing
immobilized ionic liquid
N
N
Cl
N
343 K
N
Si
(OMe)3
+
Cl
Si
(OMe)3
+
48 h
1
( )
1- Methlimidazoley
OH
OH
Silica(Aerosil300),
Toluene, reflux, 48h
PdCl2
O
Cl
N
ImmPd-IL
N
Si
SiO
+
O
ACN,
Reflux, 24h
OMe
Imm-IL
Nowadays, Immobilization of transition metal on suitable
supports solves the problem of contamination of product
with metal/ligand residue and also decreases the organic
waste from the reaction work up, thus attains improvement
of green methodology [16]. Recently, Milk et al. and Her-
mecz et al. reported the homogenous rhodium catalyst for
transfer hydrogenation of a,b-unsaturated carbonyls in ionic
liquid [17, 18]. Hence, the development of heterogeneous
immobilized metal ionic liquid on solid support is highly
desirable for organic transformation. Synthesis and charac-
terization of immobilized metal ion-containing ionic liquid
(ImmM-IL) and its applications has been explored in various
organic transformations [19, 20]. Recently, we reported
ImmPd-IL as an efficient catalyst for alkoxycarbonylation,
aminocarbonylation and for carbonylative Suzuki coupling
reaction [21, 22]. Continuing our ongoing research on the
development of efficient, heterogeneous catalysed chemo-
selective transfer hydrogenation [23], herein we report Im-
mPd-IL as a versatile catalyst for chemoselectivity transfer
hydrogenation of a,b-unsaturated carbonyls using
HCOONH4 as hydrogen donor (Scheme 1).
according to our previous reports [19–22]. All the products
are well known in literature and were characterized and
confirmed by GC, GCMS, 1H NMR and 13C NMR spectra.
2.2 Preparation of ImmPd-IL
In a dry round bottom flask, 3-trimethoxysilylpropyl
chloride (0.690 mol) and N-methylimidazole (0.690 mol)
were added under nitrogen atmosphere and resulting
reaction mixture was refluxed for 48 h. After completion,
the reaction mixture was cooled to room temperature,
washed with dry ethyl acetate. The obtained residue was
dried at room temperature under reduced pressure for
2 days and then stored at 253 K under dry nitrogen
condition.
In the next step, 1-methyl-3-(3-trimethoxysilylpropyl)
imidazolium chloride and silica (Aerosil 300, surface area
300 m2 g-1, calcined at 573 K for 1.5 h in air) (weight
ratio 1 : 1) were added in a round bottom flask containing
dry toluene and were refluxed for 48 h under nitrogen
atmosphere. Thereafter, the reaction mixture was cooled at
room temperature; the resulting mass was filtered by using
glass filter. The obtained residue was washed several times
with dichloromethane to remove the excess ionic liquid.
This obtained residue was denoted as Imm-IL. In the last
step, PdCl2 and Imm-IL were added in acetonitrile and
refluxed for 48 h. The resulting suspension was filtered by
using glass filter and washed with acetone till removal of
excess metal chloride and acetonitrile (Scheme 2).
2 Experimental
2.1 Materials and Method
All chemicals and reagents were procured from Aldrich
and WAKO.The catalyst ImmPd-IL was prepared
123

Chemoselective Transfer Hydrogenation of a,b-Unsaturated Carbonyls
1805
Table 1 Effect of catalyst and catalyst loading on transfer hydro-
genation of a,b-unsaturated carbonyl compound
Table 2 Effect of various types of hydrogen donar on transfer
hydrogenation of a,b-unsaturated carbonyl compound
Entry
Catalyst
Catalyst
loading
(mol %)
Conversion
(%)a
Selectivity
(2a:3a)
Entry
Hydrogen donar
Conversion
(%)a
Selectivity
(2a:3a)
1
2
3
4
5
HCOONH4
99
18
24
70
05
99:01
99:01
99:01
98:02
99:01
Catalyst screening
HCOONa
1
2
3
4
5
ImmPd-IL
2
2
2
2
2
99
39
35
90
84
99:01
40:60
46:54
67:33
38:62
HCOOK
Pd/C
NH2-NH2.H2O
HCOOH ? Et3N(1:1))
Pd(OH)/C
PS-TPP-Pd
Pd(OAc)2
Reaction conditions: Benzylideneacetophenone (1 mmol), ImmPd-IL
(2 mol %), hydrogen donar (3 mmol), toluene (10 ml), temperature
(90 °C), time (12 h)
Catalyst loading
a
6
7
8
ImmPd-IL
1
2
5
43
99
99
99:01
99:01
98:02
Conversion based on GC analysis
ImmPd-IL
ImmPd-IL
Firstly, to compare the catalytic activity of ImmPd-IL, we
screened various heterogeneous catalysts such as 10 % Pd/
C, Pd(OH)/C and PS-TPP-Pd (Table 1, entries 1–4) and
homogeneous Pd(OAc)2 (Table 1, entry 5) but among them
ImmPd-IL was found to be the best catalyst providing 99 %
conversion with excellent selectivity (99 %) of the desired
product (Table 1, entry 1). we studied the catalyst loading
ranging from 1 to 5 mol % and it was found that 2 mol % of
ImmPd-IL catalyst is sufficient to catalyze the reac-
tion.(Table 1, entries 6–8). Next, we have studied the effect
of various hydrogen donors; it was observed that HCOONH4
attained 99 % conversion with excellent chemoselectivity
(99 %) of the desired product (Table 2, entry 1).Other
hydrogen donors such as HCOONa, HCOOK, NH2-NH2.H2
O and mixture of HCOOH ? Et3N (1:1) gave lower con-
version (Table 2, entries 2–5).
Reaction condition:Benzylideneacetophenone (1 mmol), HCOONH4
(3 mmol), toluene (10 ml), temperature (90 °C), time (12 h)
a
Conversion based on GC analysis
2.3 General Procedure of Chemoselective Transfer
Hydrogenation of a,b-Unsaturated Carbonyl
Compounds
The round bottom flask containing a,b-unsaturated car-
bonyl (1 mmol), HCOONH4 (3 mmol) and ImmPd-IL
(2 mol %) was added toluene (10 ml) and reaction mixture
heated at 90 °C for 12 h. The progress of the reaction was
monitored by using TLC and GC analysis. After comple-
tion, the reaction mixture was cooled to room temperature
and then filtered to separate catalyst. The filtrate was then
evaporated under high vacuum and obtained residue was
purified by column chromatography using silica gel
(100–200 mesh size) with pet ether and ethyl acetate (95:5)
to give the desired pure product.
In the next set of experiment, we have checked the effect
of solvents. Polar solvents like DMF (72 %), water (14 %)
and ethanol (64 %) THF (30 %) and dichloromethane
(05 %) did not provide complete conversion of starting
material (Table 3, entries 1–5). However, non polar solvent
toluene gave complete conversion with 99 % chemoselec-
tivity towards desired product (Table 3, entry 6). Therefore,
toluene was chosen as best solvent for the further study.
Further, we have checked the effect of hydrogen donor
concentration (HCOONH4). It was observed that employing
1 mmol of HCOONH4, the lower yield of the desired
product was obtained (34 %) (Table 3,entry 7). However,
with further increase in hydrogen source up to 3 mmol
excellent conversion and selectivity was obtained (Table 3,
entry 9). No profound effect on conversion and selectivity
was observed when we increased the concentration of
HCOONH4 up to 5 mmol (Table 3, entry 10). Also we have
studied the effect of temperature and time. While decreasing
the temperature from 90 to 70 °C, conversion decreases up
to 66 % (Table 3, entries 11,12) and 12 h were sufficient to
3 Results and Discussion
3.1 Chemoselective Transfer Hydrogenation of a,b-
Unsaturated Carbonyl Compounds
The reaction parameters were optimized using ImmPd-IL
catalyst and ammonium formate as a hydrogen source for
chemoselective transfer hydrogenation of benzylideneace-
tophenone as a model reaction. The reaction parameters
include catalyst screening, the effect of catalyst loading,
and effect of various hydrogen donors, reaction time and
temperature. The obtained results are summarized in
Tables 1 and 2.
123

1806
N. M. Patil et al.
Temp (oC)
Time (h)
Conversion (%)a
(%)
Selectivity
(2a:3a)
Table 3 Effect of reaction
parameter on transfer
hydrogenation of
Entry
Solvent
HCOONH4
(mmol)
benzylideneacetophenone
Effect of solvent
1
2
3
4
5
6
DMF
3
3
3
3
3
3
100
100
90
12
12
12
12
12
12
72
14
70
30
05
99
98:02
99:01
96:04
99:01
99:01
99:01
Water
Ethanol
THF
100
90
DCM
Toluene
90
Effect of hydrogen donar concentration
7
Toluene
Toluene
Toluene
Toluene
1
2
3
5
90
90
90
90
12
12
12
12
34
78
99
99
99:01
99:01
99:01
98:02
8
9
10
Effect of temperature
Reaction condition:
Benzylideneacetophenone
(1 mmol), ImmPd-IL
(2 mol %), HCOONH4
(3 mmol), solvent (10 ml),
temperature (90 °C), time
(12 h)
11
12
Toluene
Toluene
3
3
70
90
12
12
66
99
99:01
99:01
Effect of Time
13
14
15
Toluene
3
3
3
90
90
90
6
48
74
99
99:01
99:01
99:01
Toluene
Toluene
8
a
Conversion based on GC
12
analysis
Conversion (%)a
99
Selectivity (2a:3a)
99:01
Table 4 Chemoselective
transfer hydrogenation of
a,b-unsaturated carbonyl
compounds
Entry
1
Substrate
Product
2
94
91
90
84
82
80
76
96
98
99:01
99:01
99:01
97:03
96:04
99:01
99:01
100:00
100:00
3
4
5
6
7
8
9
10
123

Chemoselective Transfer Hydrogenation of a,b-Unsaturated Carbonyls
Table 4 continued
1807
Entry
Substrate
Product
Conversion (%)a
92
Selectivity (2a:3a)
99:01
11
12
13
14
87
84
82
98:02
100:00
100:00
Reaction condition:
Benzylideneacetophenone
(1 mmol), ImmPd-IL
(2 mol %), HCOONH4
(3 mmol), toluene (10 ml),
temperature (90 °C), time
(12 h)
15
99
97
100:00
99:01
16b
a
Conversion based on GC
analysis
b
6 mmol of HCOONH4
required for complete the
reduction
17b
81
99:01
convert all starting material into the corresponding product
(Table 3, entries 13,15). Hence, the best optimized reaction
parameters for chemoselective transfer hydrogenation for
1 mmol of benzylideneacetophenone were: ImmPd-IL
(2 mol %), HCOONH4 (3 mmol), toluene as solvent
(10 ml) and temperature 90 °C for 12 h.
With these optimized reaction conditions in hand, we
have checked the activity of ImmPd-IL catalyst for
chemoselective transfer hydrogenation of various a,b-
unsaturated carbonyls, esters, amides and nitriles (Table 4,
entries 1–17). Hydrogenation of benzylideneacetophenone
gave corresponding 1,4-reduced product in excellent yield
with 99 % selectivity (Table 4, entry 1). Electron donating
groups on phenyl ring does not have any effect on selec-
tivity (Table 4, entries 2–4); however, electron withdraw-
ing chloro group led slightly lower conversion with
appreciable chemoselectivity without dechlorination
(Table 4, entries 5,6).we examined various heterocyclic
enones, both substrates reacts smoothly giving corre-
sponding product with good conversion and excellent
selectivity (Table 4, entries 7,8). Isophorone and cyclo-
hexenone were achieved with ease giving good yield with
100 % selectivity (Table 4, entries 9, 10). Benzylidene-
acetone was also selectively reduced giving corresponding
product in good conversion and selectivity (Table 4, entry
11).
Fig. 1 Recyclability study of the ImmPd-IL Catalyst
12–15).While employing multiple bonds for chemoselec-
tive reduction, complete reduction of triple (Table 4, entry
16) and olefinic bond were observed (Table 4, entry 17). In
general, the developed ImmPd-IL catalyst could facilitate
the conjugate reduction of various a,b-unsaturated car-
bonyl derivatives giving excellent yield and selectivity of
the desired product.
Furthermore, we have extended our protocol for various
functional groups such as a,b-unsaturated aldehyde, esters,
amides and nitriles. It is noteworthy to mention that all
these functionalities were well tolerated under present
catalytic system giving good conversion with 100 % che-
moselectivity towards olefinic bond (Table 4, entries
3.2 Recycle Study
In order to make our catalytic system more economical,
after completion of the reaction, the reaction mixture was
cooled to room temperature and the reaction mixture was
123

1808
N. M. Patil et al.
Fig. 2 XPS analysis of the
ImmPd-IL catalyst a XPS
survey spectrum b Pd3d region
c Cl2p region
filtered to separate catalyst. The obtained residue was
washed several times with distilled water followed by
methanol to remove all organic residues. The catalyst was
then dried under high vacuum and reused for next run. The
recyclability study shows that the catalyst could efficiently
recycle up to four consecutive cycles without significant
lose on in catalytic activity (Fig. 1).To check the leaching
of palladium, we have performed ICP-AES analysis the
result shows that palladium content in solution was below
detectable level (0.001 ppm). We have also performed hot
filtration test to check the Pd leaching. The experimental
result suggests that the palladium metal did not leach from
support.
4 Conclusion
In summery, the present protocol reports a simple, efficient,
recyclable catalytic system for chemoselective transfer
hydrogenation of various a,b-unsaturated carbonyl com-
pound by ImmPd-IL as a versatile heterogeneous catalyst.
The present methodology offers chemoselective 1,4-
reduction of wide range of substrates with various func-
tionalities such as ketones, aldehydes, esters, amides and
nitrile affording excellent yield and selectivity of the
desired product. Also, the catalyst was reused for four
recycles without significant loss in the catalytic activity.
Acknowledgments The author (N. M. Patil) is greatly thankful to
the UGC-SAP (University Grant Commission, India) for providing
the Senior Research Fellowship. XPS measurements were conducted
at the Research Hub for Advanced Nano Characterization, the Uni-
versity of Tokyo, supported by the Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan. This work is sup-
ported by JSPS and DST under the Japan-India Science Cooperative
Program.
3.3 XPS Analysis
The XPS spectra’s were studied for the fresh ImmPd-IL and
the 4th recycle catalyst to determine valence state of cata-
lyst (Fig. 2). The wide scans studied show that no change in
XPS spectra, which suggests, there was no change in the
fresh and recycled catalysts. In Pd 3d region fresh catalyst
shows two peak at 336.8 and 342 eV and 4th recycle cat-
alyst also shows two peak at 336.7 and 341.9 eV with
respective to 3d5/2 and 3d3/2 for the Pd?2 species. These
results indicate that fresh catalyst was not reduced after 4th
recycle. For Cl 2p region of the fresh and 4th recycle
ImmPd-IL catalyst no change was observed (Fig. 2c).
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