Development of molecular sieves-supported palladium catalyst and chemoselective hydrogenation of unsaturated bonds in the presence of nitro groups

Article abstract of DOI:10.1002/adsc.200900316

The chemoselective hydrogenation of unsaturated bonds and azide functionalities is achieved in the presence of nitro groups by a heterogeneous palladium catalyst supported on molecular sieves (MS3A). The present method shows a widerange of applicability with regard to substrates and the catalyst can be easily prepared and reused at least three times without any loss of activity.

Full text of DOI:10.1002/adsc.200900316

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DOI: 10.1002/adsc.200900316
Development of Molecular Sieves-Supported Palladium Catalyst
and Chemoselective Hydrogenation of Unsaturated Bonds in the
Presence of Nitro Groups
Tomohiro Maegawa,a,b Tohru Takahashi,a Masatoshi Yoshimura,c
Hiroyasu Suzuka,c Yasunari Monguchi,a and Hironao Sajikia,*
a
Laboratory of Organic Chemistry, Department of Organic and Medicinal Chemistry, School of Pharmaceutical Sciences,
Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan
Fax : (+81) 58-237-5979; e-mail: sajiki@gifu-pu.ac.jp
Current address: Graduate School of Pharmaceutical Sciences, Osaka University, 1–6 Yamada-oka, Suita, Osaka
b
565-0871, Japan
c
N.E. Chemcat Corporation, Numazu Plant, 678 Ipponmatsu, Numazu, Shizuoka 410-0314, Japan
Received: May 7, 2009; Revised: June 26, 2009; Published online: September 10, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900316.
Abstract: The chemoselective hydrogenation of un-
saturated bonds and azide functionalities is ach-
ieved in the presence of nitro groups by a heteroge-
neous palladium catalyst supported on molecular
sieves (MS3A). The present method shows a wide-
range of applicability with regard to substrates and
the catalyst can be easily prepared and reused at
least three times without any loss of activity.
erogeneous catalytic hydrogenations are more favora-
ble but no method exists to date.
During the course of investigations on a chemose-
lective hydrogenation, we found that the addition of
amines and sulfides, such as Et3N, pyridine and di-
phenyl sulfide, effectively works as a partial catalyst
poison to control the catalytic activity of Pd/C. As a
result, we developed Pd/C-catalyzed chemoselective
hydrogenation methods between various reducible
functions using the appropriate catalyst poison.[6] As
an extension of these methods, we prepared the isola-
ble amine- and sulfur-poisoned catalysts; i.e., the
Pd/C-ethylenediamine complex [Pd/C(en)],[7] Pd-poly-
ethyleneimine complex (Pd/PEI).[8] and Pd/C-diphen-
Keywords: chemoselective hydrogenation; hetero-
geneous catalysis; molecular sieves; nitro com-
pounds; palladium
yl sulfide complex [Pd/CACHTNUTGRNEUNG
(Ph2S)],[9] for the chemoselec-
tive hydrogenations (Figure 1).
Chemoselective hydrogenation is one of the most de-
Furthermore, we also developed a silk fibroin, a
sirable reactions in organic synthesis, such as the total protein produced by silkworms possessing very few
synthesis of complex molecules bearing many reduci- residues of sulfur-containing amino acids, a supported
ble functional groups.[1] The nitro group is a useful
functional group as precursor of amine and oxime
functionalities and can be easily introduced on an aro-
matic ring by an electrophilic substitution reaction.
Since aromatic nitro groups are very susceptible to
transition metal-catalyzed hydrogenation,[1b] it is un-
fortunately difficult to achieve the selective hydroge-
nation of unsaturated bonds while maintaining the
nitro functions intact, the only exception being a sole
hydrogenation method using homogeneous Wilkin-
sonꢀs catalyst.[2] Furthermore, such a chemoselective
transformation is also extremely difficult using other
reductive methods and very few potential methods
using bakerꢀs yeast,[3] a metal hydride,[4] and siloxane[5]
Figure 1. Pd-catalyzed chemoselective hydrogenation with
are available. In terms of industrial applications, het- combination of various catalytic poisons.
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Tomohiro Maegawa et al.
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Pd-catalyst, and a Pd-fibroin complex (Pd/Fib),[10] as
the selective hydrogenation catalyst of C-C or N-C
multiple bonds in the presence of many other reduci-
ble functionalities as summarized in Figure 1. Based
on these results, we noticed the significance of the
catalyst support for an excellent chemoselectivity.
Many types of zeolite possessing wide varieties of
surface area, pore size, polarity of the inside cavity,
and so on were reported in the literature, depending
on the preparation methods.[11] Molecular sieves (MS)
are well known as a representative zeolite and they
are widely utilized in many chemical fields. MS pos-
sessing different pore sizes are commercially available
and we expected that such characteristics may affect
the reactivity of the Pd catalysts. Therefore, we chose
an MS as the catalyst support for the chemoselective
hydrogenation. Herein, we report the preparation of
novel MS-supported Pd catalysts (Pd/MS) and the
Table 1. Catalytic activity for the hydrogenation of 4-ethyn-
AHCTUNGTRENNUNG
ylanisole.[a]
Entry
Catalyst
1:2:3[b]
1
2
3
4
Pd/MS3A
Pd/MS4A
Pd/MS5A
Pd/MS13X
0:10:90
0:84:16
31:69:0
63:37:0
[a]
The reaction was carried out using 0.25 mmol of 4-eth-
AHCTUNGTREyNGNUN nylanisole and 10 wt% of the catalyst in CH3OH at
room temperature for 24 h under an ordinary H2 atmos-
phere.
The ratio was determined by H NMR.
[b]
1
chemoselective hydrogenation of olefin, acetylene tries 8 and 9) and aromatic ketones (entries 9 and 10)
and azide functionalities in the presence of a nitro were tolerated under the Pd/MS3A-catalyzed hydro-
group using a Pd/MS catalyst.
genation conditions even after 24 h.
Initially, we prepared the 0.5% Pd-MS (0.5% Pd
During the investigation, we surprisingly found that
metal vs. MS) complex (Scheme 1).[10] Different types Pd/MS3A-catalyzed hydrogenation conditions never
of molecular sieves (MS3A, 4A, 5A and 13X) were affected an aromatic nitro group (Scheme 2). The aro-
soaked in a CH3OH solution of PdACTHNUTRGNEN(UG OAc)2 and stirred matic nitro groups are very susceptible to hydrogena-
for 6 days until the rust-colored supernatant solution tion and easily reduced to the corresponding amines
turned clear. The suspension was then collected by fil- via nitroso intermediates. Therefore, it is extremely
tration and washed with CH3OH and H2O to give the hard to logically achieve the chemoselective hydroge-
Pd/MS catalyst as a gray powder. Pd metal absorbed nation of unsaturated multiple bonds in the presence
on the MS was nearly 0.5 wt% of the catalyst based of nitro groups.[1]
on XRF analysis, and the XANES analysis of the
Pd/MS catalyst showed that most of (>90%) the ab- ty of Pd/MS3A for the chemoselective hydrogenation
sorbed Pd species existed as Pd(0). of unsaturated multiple bonds of diverse nitro-con-
Such a background led us to explore the applicabili-
We then examined the catalyst activities against the taining compounds (Table 3). Nitro functionalities as
hydrogenation of each catalyst using 4-ethynylanisole well as the aliphatic nitro function remained intact
as the substrate (Table 1). Interestingly, each catalyst during the 24 h hydrogenation. The chemoselective
showed a different catalyst activity. Since 0.5% hydrogenation between the nitro groups and multiple
Pd/MS3A indicated an appropriate and mild reactivi- bonds as well as azide groups (entries 1–5) was com-
ty toward the hydrogenation of the unsaturated bond, pletely achieved. Other reducible functionalities such
therefore, we expect that the Pd/MS3A would exhibit as the aryl bromide, N-Cbz and benzyl ester were also
a
novel chemoselectivity for the hydrogenation tolerated under these conditions (entries 6–8).
among the various reducible functionalities. The STEM analysis showed that Pd on the
We attempted the hydrogenation of a variety of Pd/MS3A catalyst existed as a nanoparticle [<10 nm
substrates possessing different types of reducible func- (<100 ꢂ)] and most of the Pd cluster may exist on
tionalities within the molecule (Table 2). Consequent- the surface of the MS, not inside the cavity (Figure 2).
ly, unsaturated bonds including the azide were com- This is also supported by the EXAFS analysis
pletely hydrogenated to the corresponding saturated (Figure 3) because of few correlations between Pd
bonds (entries 1–8, 10 and 11). No hydrogenolysis of and Si or Al atoms in MS. Surprisingly, the surface
benzyl esters (entries 2–4), benzyl ethers (entries 5 area of the Pd metal of Pd/MS3A (22 m2 gÀ1 Pd) was
and 6), aromatic bromide (entry 7) and N-Cbz only one-tenth of that of Pd/Al2O3 by a surface area
(entry 11) were observed. Furthermore, nitriles (en- analysis using the CO adsorption method. The postu-
Scheme 1. Preparation of the Pd/MS catalyst.
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Development of Molecular Sieves-Supported Palladium Catalyst
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Table 2. Chemoselective hydrogenation using heterogeneous Table 3. Chemoselective hydrogenation in the presence of a
Pd/MS3A.[a]
nitro group using heterogeneous Pd/MS3A.[a]
Entry Substrate
1[b]
Product
Yield [%} Entry Substrate
Product
Yield
[%]
83
1
95
2
3
94
91
2
3
90
4
5
56[c]
98[b]
98
4
90[b]
6
100
5
6
68[c]
96
7
8
72
92[d]
7
94
98
9
95
8
10
94
95
[a]
The reaction was carried out using 0.25 mmol of substrate
and 10 wt% of 0.5% Pd/MS3A in CH3OH at room tempera-
ture for 24 h under an ordinary H2 atmosphere.
A trace amount of a diamino compound was detected
AHCTUNGTRENNUNG
[b]
[c]
11
[a]
The reaction was carried out using 0.25 mmol of sub-
strate and 10 wt% of 0.5% Pd/MS3A in CH3OH at room
temperature for 24 h under an ordinary H2 atmosphere.
The reaction was performed for 36 h.
The low yield of product was due to its volatile nature.
6% of starting material unchanged after 24 h.
Pd/MS catalyst with different pores size may be due
to the adsorption affinity of substrate into the cavity
(Table 1).
Finally, we examined the reusability of the
Pd/MS3A. As a result, the catalyst could be reused at
least three times without any significant loss of activi-
[b]
[c]
[d]
lated expression mechanism of the chemoselectivity ty and without a reactivation process (Table 4).
of the Pd/MS3A-catalyzed hydrogenation could be In conclusion, we have developed a novel heteroge-
correlated with the reduction of the active surface neous and chemoselective hydrogenation catalyst,
area of Pd metal although it is not clear why the Pd Pd/MS3A. Only unsaturated multiple bonds including
nanoparticle on MS3A showed such a small surface azide functions were reduced without reduction of
area. The differences of catalyst activity between each other reducible functionalities including nitro groups
Scheme 2. Chemoselective hydrogenation in the presence of a nitro group.
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Tomohiro Maegawa et al.
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chemoselective hydrogenation. The present method
indicates a wide applicability of substrates and has ad-
vantages of easy preparation, handling and reusability
of the catalyst.
Experimental Section
Preparation of Pd/MS catalyst
To the solution of PdACHTUNTRGNEUNG(OAc)2 (52.7 mg, 0.23 mmol, 0.5 wt%
vs. MS) in CH3OH (50 mL) were added molecular sieves
(powder) (5.0 g) and stirred for 6 days until the color of the
supernatant of the suspension turned clear. The suspension
was then filtered and the obtained solid was washed with
CH3OH and H2O and dried under vacuum to give the 0.5%
Pd/MS catalyst as a grey powder.
Figure 2. STEM of 0.5% Pd/MS3A.
Chemoselective Hydrogenation
The mixture of the substrate (0.25 mmol), 0.5% Pd/MS3A
(10 wt% of substrate) and CH3OH (1.0 mL) was exposed to
H2 gas using an H2-filled balloon, and then stirred at room
temperature for 24 h. The reaction mixture was filtered
through a membrane filter (Millipore, Millexꢃ-LH, 0.45 mm)
and the filtrate was concentrated under reduced pressure to
produce the product.
XANES experiments were performed at the BL14B2 in
the SPring-8 with the approval of the Japan Synchrotron Ra-
diation Research Institute (JASRI) (proposal no.
2008 A1896).
Table 4. Reuse of the Pd/MS3A catalyst.[a]
Recycle
Selectivity (1:2)
Yield [%]
1
2
3
0:100
0:100
0:100
100
100
100
[a]
The substrate (0.25 mmol), Pd/MS3A (10 wt%) and
CH3OH (1.0 mL) was used.
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Figure 3. Pd K-edge K3c(k) EXAFS Fourier transforms of 0.5% Pd/MS3A and Pd foil.
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Adv. Synth. Catal. 2009, 351, 2091 – 2095

Development of Molecular Sieves-Supported Palladium Catalyst
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Adv. Synth. Catal. 2009, 351, 2091 – 2095
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2095