Solid supported Pd(0): An efficient recyclable heterogeneous catalyst for chemoselective reduction of nitroarenes

Article abstract of DOI:10.1016/j.tetlet.2012.06.132

Solid supported palladium(0) (SS-Pd) catalyzed highly chemoselective reduction of nitroarenes to the corresponding anilines was accomplished under a milder reaction condition. This catalyst showed high compatibility with various reducing agents (NaBH₄, Et₃SiH, and NH₂NH ₂·H₂O) and a large number of reducible functional groups such as sulfonamide, amides, carboxylic acid, ester, alcohol, halide, hetero cycle, nitrile, alkene, carbonyl, O-benzyl, and N-benzyl were tolerated. Most of the reactions were clean and high yielding. The SS-Pd catalyst could be recycled up to seven runs without significant loss of activity.

Full text of DOI:10.1016/j.tetlet.2012.06.132

Tetrahedron Letters 53 (2012) 4858–4861
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Solid supported Pd(0): an efficient recyclable heterogeneous catalyst for
chemoselective reduction of nitroarenes q
⇑
Arun K. Shil, Dharminder Sharma, Nitul Ranjan Guha, Pralay Das
Natural Plant Products Division, CSIR-Institute of Himalayan Bioresouce Technology, Palampur-176061, H.P., India
a r t i c l e i n f o
a b s t r a c t
Article history:
Solid supported palladium(0) (SS-Pd) catalyzed highly chemoselective reduction of nitroarenes to the
corresponding anilines was accomplished under a milder reaction condition. This catalyst showed high
compatibility with various reducing agents (NaBH4, Et3SiH, and NH2NH2ÁH2O) and a large number of
reducible functional groups such as sulfonamide, amides, carboxylic acid, ester, alcohol, halide, hetero
cycle, nitrile, alkene, carbonyl, O-benzyl, and N-benzyl were tolerated. Most of the reactions were clean
and high yielding. The SS-Pd catalyst could be recycled up to seven runs without significant loss of
activity.
Received 7 April 2012
Revised 26 June 2012
Accepted 28 June 2012
Available online 6 July 2012
Keywords:
Nitroarenes
Chemoselective reduction
Solid supported palladium
Nano/micro particles
Milder reducing source
Ó 2012 Elsevier Ltd. All rights reserved.
Amino compounds are the main precursor or intermediate for a
number of valuable molecules such as dyes, pesticides, herbicides,
and agrochemicals.1 Reduction of nitroarenes in a selective manner
is the best route to obtain industrially important aryl amines. Pal-
ladium is an active transition metal of choice, which has been used
in different catalytic forms to reduce organo nitro derivatives.
Pd(OAc)2/polymer supported formate,2 Pd-carbon nanofiber
Herein, we report convenient methodologies for nitroarene
reduction in the presence of SS-Pd as a ligand-free recyclable het-
erogeneous catalyst under milder reducing agents.
The SS-Pd catalyst was prepared following our previous report8
and SEM analysis was performed to see nano/microparticles depo-
sition over the solid surface (Fig. 1). In our previous studies, we
realized that nanoparticles of palladium deposited inside the solid
matrix were difficult to analyze by transmission electron micros-
copy (TEM). Here, for the first time we prepared the powdered
form of borohydride exchanged amberlite resin for in situ conver-
sion of Pd(II) to Pd(0) and their simultaneous deposition over solid
matrix. The water suspension of the dispersed solid supported
(CNF)/H2,3 Pd(OAc)2/silicon hydride,4 and Pd-PEG/H2 have been
5
reported for the transformation of nitroarenes to corresponding
anilines. It is well known that sodium borohydride has less poten-
tiality to reduce nitro compounds to corresponding amines in the
absence of additives.6 In addition, usually reduction of nitroarenes
with NaBH4 stops at intermediate stage of azo, azoxy, and hydrazo
derivatives.7 Besides this problem, recyclability of catalyst, high
loading of reducing agent, metal contamination, cost of the re-
agent, and high pressure apparatus for hydrogenation make the
processes economically unfavorable as well as hazardous. Hence,
an alternative fast, cost effective, milder, and chemoselective
reduction of nitroarenes with negligible metal contamination is
of high demand.
´
Pd(0) (SS-Pd) was further characterized by TEM for nanoparticles
analysis of Pd(0) (Fig. 2). Further, both the catalysts SS-Pd and
´
SS-Pd were tested for different nitroarene reduction and no signif-
icant effect on product yields was observed. Due to easy handling,
purification, reusability, and same reactivity, SS-Pd was further ex-
plored for reduction of nitroarenes.
Initially to search for the optimum reaction condition, reducing
agent, best catalytic system, catalyst concentration, solvent, and
temperature, 4-nitrotoluene was considered as test substrate.
The combination of SS-Pd (2 mol % Pd) and MeOH:H2O (3:7) was
found to be very effective for both NaBH4 and NH2NH2.H2O reduc-
ing agents which gave 97 and 98% yields respectively of the corre-
sponding amine 1. Interestingly, Et3SiH was also found to be
effective with SS-Pd (3 mol % Pd) in THF solvent for the same
reduction and ended with 82% yield at room temperature. The
SS-Pd and NaBH4 combination was also employed on the same
Recently our group described the synthesis of solid supported
palladium(0) (SS-Pd) nano/microparticles as heterogeneous cata-
lyst and their applications in cross coupling8a and oxidation8b
reactions.
q
IHBT communication No. 2283.
⇑
Corresponding author. Fax: +91 1894 230433.
E-mail addresses: pdas@ihbt.res.in, pdas_nbu@yahoo.com (P. Das).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.132

A. K. Shil et al. / Tetrahedron Letters 53 (2012) 4858–4861
4859
Pd
SS-Pd(0)
SS-Pd
Figure 1. Scanning Electron Micrograph (SEM) image of SS-Pd.
Table 1
Reduction of nitroarenes using milder reducing sources
NO2
NH2
Method A/B/C
1-3.5 h
R
R
1-25
Time(h)/Yielda(%)
Entry
Product
A
B
C
NH2
1
2
1.5/97
3/98
1/82, (23b)
2.5/96
1
H3C
NH2
1.5/99
1/92
2
H3CO
NH2
3
4
1.5/96
1/93
1.5/90
1/90
3/95
3
H3COCHN
NH2
1.5/82
4
Cl
Figure 2. Transmission electron microscope (TEM) image of SS-Pd.
NH2
5
6
1.5/90
2.5/80
1/85
1/72
3/50
substrate up to 5 gm scale and gave 1 in 95% yield (GC-MS).
Furthermore, hydrogenation with the ex situ produced molecular
hydrogen that resulted in poor conversion of 1 (23%) (Table 1, en-
try 1).
5
6
NH2
3.5/76
To see the scope, the SS-Pd catalyst was further explored with
the three reducing sources (NaBH4/Et3SiH/NH2NH2.H2O) for differ-
ent representative nitroarenes (Table 1; 2–6). Due to comparative
results in foremost reactions, further importance for the selection
of reducing agents was given on chemoselective nitroarenes reduc-
tion through easy accessible, non-hazardous, trouble-free product
separation, and cost effective process. Considering these issues,
the reducing agents in combination with SS-Pd were further deter-
mined based on the functional groups with nitroarenes. Unsubsti-
tuted nitroarene under the standard SS-Pd and NaBH4 condition
afforded high yield of aniline 7. Further this combination was
found to be highly chemoselective in the presence of several reduc-
ible functional groups such as sulfonamide, amides, carboxylic
acid, ester, alcohol, halides, and nitrile (8-15). Polycyclic and het-
erocyclic nitroarenes also gave good to excellent yield of corre-
sponding amines (16 and 17). 4-nitroaniline under similar
condition gave 1,4-diamino benzene 18 in 91% yield. Similarly, in
our typical method (Method A) 1,3-dinitrobenzene resulted in
the corresponding diamino derivative 19 in an excellent yield.
As per our knowledge NH2NH2.H2O with palladium catalyst as a
reducing agent for nitroarene reduction has not yet been reported
in the literature. Regioselective reduction of dinitro compound is
N
NH2
7
8
1/98
2/90
7
NH2
8
H2NO2S
H2NOC
NH2
9
2/92
9
NH2
10
2.5/70
10
HOOC
NH2
11
11
2.5/93
COOCH3
(continued on next page)

4860
A. K. Shil et al. / Tetrahedron Letters 53 (2012) 4858–4861
NaBH4
NaBH4
+
+
4H2O
NaB(OH)4
NaB(OMe)4
SS-Pd[H2]n
+
+
4H2
4H2
Table 1 (continued)
Entry
Product
Time(h)/Yielda(%)
4MeOH
A
B
C
SS-Pd + nH2
NO2
NH2
12
13
0.66/75
12
HO
Br
NH2
1/95
1/80
I
H2
13
-H2O
NH2
NO
NHOH
NH2
14
15
14
H2
I
H2
-H2O
NH2
Method A
II
III
Pathway A
VII
1.5/97
Negligible
Major
15
H2
NC
H
N
NH2
16
Pathway B -H2O
Minor
16
17
2/99
2/94
N
H
VI
NH2
H2
Method A
N
N
17
N
N
H2
-H2O
N
IV
V
NH2
O
18
19
1.4/91
3/90
18
Scheme 1. Possible mechanistic pathways of nitroarene reduction using SS-Pd and
NaBH4
H2N
NH2
19
an important feature of nitroarene reduction. Longer reaction time
was the limitation of the previous method.2 However, regioselec-
tive product 20 was observed in the presence of Et3SiH (Method
B) and NH2NH2.H2O (Method C). High chemoselective reduction
of 3-nitrostyrene to corresponding amine 21 was observed under
SS-Pd and NH2NH2.H2O condition. Chemoselective reduction of
4-nitro acetophenone was observed under SS-Pd and NH2NH2.H2O
condition to produce 22 in 75% yield. The reduction of 4-nitrobenz-
aldehyde was reported to provide 4-toluedine as major byproduct
using PdCl2/ Et3SiH system.9 Using triethylsilane (Method B) unfor-
tunately led to 4-aminobenzyltriethylsillylether 23 as the product
in 72% yield. In the presence of NaBH4 (Method-A) O-benzyl and N-
benzyl functional groups attached to nitroarenes were well toler-
ated to give the desired products 24 and 25.
Mechanistically the reduction of nitroarenes may go through
the formation of hydroxylamine as well as azobenzene.10 To under-
stand the mechanistic pathway, two parallel reductionreactions of
nitrosobenzene II and azobenzene V were conducted following the
standard method11 (Method A). Under this condition, nitrosoben-
zene gave aniline as major product with azobenzene as by-product
(Scheme 1), whereas, azobenzene V under same conditions gave
1,2-diphenylhydrazine as major product and aniline as minor
product. Therefore, the reaction might follow pathway A than
pathway B for the nitroarene reduction to the corresponding ani-
line in Method A (Scheme 1). Similar observations were also found
in Method B and Method C.
NH2
NO2
NH2
20
20
21
22
2/75
3/80
NH2
0.66/63
1/75
21
NH2
22
H3C
O
NH2
23
24
1.5/72
O
Et3Si
23
NH2
1.5/86
2/90
24
NH2
Ph
Ph
O
The recyclability experiment of the catalyst was evaluated on 4-
nitrobenzonitrile (Supplementary data information). After comple-
tion, the reaction mixture was filtered off through a cotton bed,
washed with methanol, dried under reduced pressure, and reused
for further reaction. Up to seven runs with no significant loss of
catalytic activities were observed.
25
25
N
H
a
Otherwise stated all yields are isolated yields in three methods (A, B and C);
Method A:SS-Pd (2 mol % Pd), NaBH4 (3 equiv), MeOH:H2O (3:7), 50 oC; Method B:
SS-Pd (3 mol
% Pd), Et3SiH (4 equiv), THF, RT; Method C: SS-Pd (2 mol% Pd),
NH2NH2.H2O (3 equiv), MeOH:H2O (3:7), 80 oC;
b
GC–MS yield, H2 balloon, 2 mol% Pd, time 2 h.

A. K. Shil et al. / Tetrahedron Letters 53 (2012) 4858–4861
4861
In conclusion, we have developed solid supported nano and
References and notes
microparticles of Pd(0) (SS-Pd) as heterogeneous catalysts and
their successful application for reduction of nitroarenes to corre-
sponding amines. TEM study was performed to analyze the nano-
particles of Pd (0) deposition in the solid matrix. Easy hydrogen
transfer capability of SS-Pd has been well documented at low reac-
tion temperature with a larger substrate scope and compatible
among different reducing sources. On completion, the air and
moisture stable SS-Pd catalyst was easily separated from the reac-
tion media and recycled up to nine times with reproducible results.
Overall, SS-Pd was found to be a very efficient and versatile cata-
lyst for the reduction of nitroarenes to anilines in small and large
scale processes.
1. (a) Ono, N. The Nitro Group in Organic Synthesis; Wiley-VCH: New York, 2001;
(b) Tafesh, A. M.; Weiguny, J. Chem. Rev. 1996, 96, 2035; (c) Downing, R. S.;
Kunkeler, P. J.; Bekkum, H. V. Catal. Today 1997, 37, 121.
2. Basu, B.; Das, P.; Das, S. Mol. Diversity 2005, 9, 259.
3. Takasaki, M.; Motoyama, Y.; Higashi, K.; Yoon, S. H.; Mochida, I.; Nagashima, H.
Org. Lett. 2008, 10, 1601.
4. (a) Rahaim, R. J.; Maleczka, R. E. Org. Lett. 2005, 7, 5087; (b) Rahaim, R. J.;
Maleczka, R. E. Synthesis 2006, 3316.
5. Harraza, F. A.; El-Houta, S. E.; Killab, H. M.; Ibrahima, I. A. J. Catal. 2012, 286,
184.
6. (a) Zeynizadeh, B.; Setam-dideh, D. Synth. Commun. 2006, 36, 2699; (b)
Rahman, A.; Jonnalagadda, S. B. Catal. Lett. 2008, 123, 264; (c) Pogoreli, I.;
Filipan-Litvi, M.; Merka, S.; Ljubi, G.; Cepane, I.; Litvi, M. J. Mol. Catal. A: Chem.
2007, 274, 202; (d) Dotzauer, D. M.; Bhattacharjee, S.; Wen, Y.; Bruening, M. L.
Langmuir 1865, 2009, 25; (e) Smith, W. B. J. Heterocycl. Chem. 1987, 24, 745.
7. (a) Hutchins, R. O.; Lamson, D. W.; Rua, L.; Milewski, C.; Maryanoff, B. J. Org.
Chem. 1971, 36, 803; (b) Li, F.; Cui, J.; Qian, X.; Zhanga, R.; Xiaoa, Y. Chem.
Commum. 1901, 2005.
Acknowledgments
8. (a) Bandna Aggarwal, N.; Das, P. Tetrahedron. Lett. 2011, 52, 4954; (b) Das, P.;
Sharma, D.; Shil, A. K.; Kumari, A. Tetrahedron Lett. 2011, 52, 1176.
9. Mirza-Aghayan, M.; Boukherroub, R.; Rahimifard, M.; Bolourtchian, M. Appl.
Organomet. Chem. 2010, 24, 477.
Authors are grateful to Dr. P.S. Ahuja, Director IHBT and Bio-
technology Division for providing necessary facilities during the
course of the work. We also gratefully acknowledge financial assis-
tance from the Department of Science & Technology (Nano Mis-
sion), New Delhi (Grant No. SR/NM/NS-95/2009). AKS (SRF-CSIR),
NRG (JRF-UGC) and DS (SRF-CSIR) thank CSIR and UGC, New Delhi
for awarding fellowships.
10. Saha, A.; Ranu, B. C. J. Org. Chem. 2008, 73, 686.
11. Typical experimental procedure (Method A):
(150 mg, 1.1 mmol), SS-Pd (492 mg, 2 mol% Pd) and NaBH4 (124.77 mg,
3.3 mmol) were taken in 25 ml round bottomed flask. 3 ml of
methanol:water (3:7) was added to the mixture by syringe at room
A mixture of 4-nitrotoluene
a
a
temperature under stirring condition. After 10 min the reaction mixture was
heated at 50 °C for 1.5 h. The progress of the reaction was monitored by TLC.
On completion, the reaction mixture was extracted with ethyl acetate
(3 Â 3 ml) and dried over anhydrous Na2SO4. Evaporation of the combined
organic layer followed by silica gel (60–120 mesh) column chromatography
(Hexane:EtOAc = 80:20) over silica gel afforded 4-methylaniline 1 as a white
solid (113.7 mg, 97%); mp 40-41 °C; 1H NMR (300 MHz, CDCl3) d 2.25 (s, 3H),
3.54 (br, N–H), 6.62 (d, J = 8.1 Hz, 2H), 6.98 (d, J = 8.1 Hz, 2H); 13C NMR
(75 MHz, CDCl3) d 20.34, 115.13 (2C), 127.66, 129.63 (2C), 143.69.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.06.
132.