Hydrogenation of nitroarenes with palladium nanoparticles stabilized by alkyne derivatives in homogeneous phase

Article abstract of DOI:10.1016/j.tetlet.2015.04.116

Palladium nanoparticles stabilized by alkyne derivatives catalyzed the hydrogenation of nitroarenes to the aryl amines in homogeneous phase. The reaction of nitrobenzene proceeded smoothly with a substrate-to-palladium molar ratio (S/Pd) of 51,000 under 8 atm of H₂. The reaction under 1 atm of H₂ with an S/Pd of 1030 was completed in 4 h. A series of substituted nitroarenes, including 4-acetyl- and 4-formylnitrobenzenes, were converted to the aryl amines with high chemoselectivity.

Full text of DOI:10.1016/j.tetlet.2015.04.116

Tetrahedron Letters 56 (2015) 3913–3915
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Hydrogenation of nitroarenes with palladium nanoparticles
stabilized by alkyne derivatives in homogeneous phase
Noriyoshi Arai a, Nozomi Onodera a, Atsushi Dekita a, Junichi Hori b, Takeshi Ohkuma a,
⇑
a Division of Chemical Process Engineering and Frontier Chemistry Center, Faculty of Engineering, Hokkaido University, Sapporo, Hokkaido 060-8628, Japan
b Central Research Laboratory, Technology and Development Division, Kanto Chemical Co., Inc., Soka, Saitama 340-0003, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Palladium nanoparticles stabilized by alkyne derivatives catalyzed the hydrogenation of nitroarenes to
the aryl amines in homogeneous phase. The reaction of nitrobenzene proceeded smoothly with a
substrate-to-palladium molar ratio (S/Pd) of 51,000 under 8 atm of H2. The reaction under 1 atm of H2
with an S/Pd of 1030 was completed in 4 h. A series of substituted nitroarenes, including 4-acetyl- and
4-formylnitrobenzenes, were converted to the aryl amines with high chemoselectivity.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 22 March 2015
Revised 21 April 2015
Accepted 28 April 2015
Available online 4 May 2015
Keywords:
Palladium
Nanoparticles
Hydrogenation
Nitroarenes
Chemoselective
Hydrogenation of nitroarenes is a facile and reliable method to
produce the aryl amines, which are fundamental compounds for
the synthesis of pharmaceuticals, herbicides, dyes, and poly-
mers.1,2 Palladium(0) supported by charcoal (Pd/C) is a typical cat-
alyst for this reaction.2,3 However, chemoselective problems have
been reported when the nitroarene substrates have competitively
reducible or degradable substituents, such as formyl, cyano, and
benzylic hydroxyl groups.2,4 Improvement of the catalytic activity
(diminution of catalyst loading) is thus highly desirable from both
a practical and environmental viewpoint. Pd catalysts with organic
or inorganic additives5 and stabilized by tailored supports6 as well
as Pd-based bimetallic catalysts7 have been developed to increase
chemoselectivity toward the nitro group.2e Modification of
reaction conditions and use of specific solvents have also been
examined for this purpose.8–12
hydrogenation of nitroarenes to aryl amines with the hydrocar-
bon-supported Pd NPs 1b as homogeneous catalysts. The alkyne
derivatives on the Pd surface not only stabilize the homogeneous
feature of the NPs but also confer the chemoselective catalyst
ability.
Scheme 1. Preparation of Pd NPs 1.
Pd NPs 1b (5.0 mM DMF solution, 0.40 lmol, substrate-to-
We recently reported novel palladium nanoparticles (Pd NPs 1)
prepared from Pd(OCOCH3)2 and 2 equiv of t-C4H9OK (1a) or
NaBH4 (1b) with 10 equiv of 4-octyne in DMF at ambient temper-
ature for 12 h (Scheme 1).13 Pd NPs 1 in DMF (10 mM) were homo-
geneously dispersed and stored at ambient temperature without
the formation of aggregates for more than 1 year. 1H NMR and
mass spectroscopic measurements suggested that the Pd NPs 1
are stabilized by alkyne molecules and oligomeric compounds.13
We here describe the highly reactive and chemoselective
palladium molar ratio (S/Pd) = 10,400) efficiently catalyzed the
hydrogenation of nitrobenzene (2a, 4.0 mmol) in methanol
(4 mL) under 8 atm of H2 at 50 °C (Table 1, entry 1). The reaction
was completed in 3 h to afford aniline (3a) as the sole product.
The S/Pd per time-to-full conversion (TOFav) was 3470 hꢀ1. The
turnover number of this transformation reached 51,000 in 40 h
(entry 2). The high catalytic activity of 1b achieved complete con-
version of 2a (S/Pd = 1030) under atmospheric pressure of H2 at
25 °C in 4 h (entry 3). The TOFav of 258 hꢀ1 was more than 18 times
faster than that of the Pd/C-catalyzed reaction (TOF = 14 hꢀ1).14,15
The homogeneous property of the NPs may cause high catalytic
activity. Methanol was a solvent of choice. THF and CH3CN were
⇑
Corresponding author. Tel.: +81 11 706 6599; fax: +81 11 706 6598.
E-mail address: ohkuma@eng.hokudai.ac.jp (T. Ohkuma).
http://dx.doi.org/10.1016/j.tetlet.2015.04.116
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

3914
N. Arai et al. / Tetrahedron Letters 56 (2015) 3913–3915
Table 1
Table 2
Hydrogenation of Nitrobenzene (2a) catalyzed by Pd NPs 1ba
Hydrogenation of Nitroarenes 2 with Pd NPs 1ba
Entry
S/Pdb
Solvent
H2 (atm)
Time (h)
Yieldc (%)
2a
3a
4a
1
10,400
51,000
1030
10,600
9800
10,200
10,200
10,200
10,000
CH3OH
CH3OH
CH3OH
THF
CH3CN
AcOEt
CH2Cl2
Toluene
Hexane
8
8
1
8
8
8
8
8
8
3
40
4
3
3
3
3
3
3
0
0
0
0
0
96
30
7
96
99e
98
97
96
3
67
79
73
0
0
0
0
0
1
0
2d
3f
4
5
6
7
8
ndg
4
9
23
a
Unless otherwise stated, reactions were conducted at 50 °C using 4.0 mmol of
2a in solvent containing Pd NPs 1b.
b
Substrate/Pd molar ratio.
c
Determined by 1H NMR analysis using 1,3,5-trimethoxybenzene as an internal
Entry
2
S/Pdb
Solvent
H2 (atm)
Time (h)
Yieldc (%)
standard. 0% means the corresponding compound was not detected.
d
Reaction using 10.0 mmol of 2a.
The isolated yield by distillation was 80%.
Reaction at 25 °C.
1
2
3
4
2b
2c
2d
2e
2f
2g
2g
2h
2h
2i
2j
2j
2k
2l
2m
2n
5000
4700
4900
5000
2500
2500
2500
4400
4300
2100
4100
1100
2500
2100
2000
5100
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
THF
THF
CH3OH
THF
8
8
8
8
8
8
8
8
8
8
8
1
8
8
8
8
7
3.5
16
12
5
5
26
5
>99 (81)
99 (93)
99 (83)
>99 (91)
>99 (97)
53e
e
f
g
Not determined because the signals of 4a and toluene were overlapped.
5
6d
7f
66 (56)g,h
also effective solvents (entries 4 and 5). However, the use of several
other polar and less polar solvents resulted in slower reaction rates
(entries 6–9). A reaction intermediate hydroxyaniline (4a) was
detected in some cases.
8
9
95h
12.5
8
8
99 (93)
88h
>99 (97)
>99
99 (95)
98 (94)
>99 (95)
>99 (95)
10d
11d
12i
13
14
15
16
THF
CH3OH
THF
2
We then applied the hydrogenation catalyzed by the Pd NPs 1b
to a series of substituted nitrobenzenes 2. These results are listed
in Table 2. Sterically hindered 2-methylnitrobenzene (2b) was
completely hydrogenated to 2-methylaniline (3b) with an S/Pd of
5000 under 8 atm of H2 in 7 h (entry 1). The phenolic hydroxyl
group of 2c did not retard the reaction to afford 3c as a sole product
(entry 2). Methoxyanilines 3d and 3e were also obtained quantita-
tively (entries 3 and 4). The benzamido group at the 2 position was
left intact through the hydrogenation of 2f (entry 5). The reaction
of 4-chloronitrobenzene (2g) in THF at 30 °C gave 4-chloroaniline
(3g) in 53% yield accompanied by 4-chlorophenylhydroxyamine
(4g) (20%), an intermediate of the hydrogenation, and the dechlo-
rinated product 3a (27%) (entry 6).16,17 An addition of 20 equiv of
TMEDA to Pd suppressed the elimination of chloride (entry 7).
The yield of 3g increased to 66% without the formation of a detect-
able amount of 3a, although the reaction rate was slowed. When
the hydrogenation was conducted in methanol, the yield of 3g
was decreased with the formation of many byproducts, including
the dechlorinated compounds. The hydrogenation of 2h in THF
quantitatively afforded the desired product 3h without injury to
the benzylic hydroxyl group, which could be removed by the
Pd/C-catalyzed hydrogenolysis (entry 9).18 Small amounts of
unidentified compounds were observed in methanol (entry 8).
Aromatic aldehydes and ketones are known to be hydrogenated
readily with the Pd/C catalyst.18 Thus, the Pd/C-catalyzed hydro-
genation of nitroarenes with acyl and formyl groups on the arene
rings results in a mixture of products.4,19 When 4-formylnitroben-
zene (2i) was hydrogenated with the Pd NPs 1b under 8 atm of H2
in THF at 30 °C, 4-formylaniline (3i) was obtained in 88% yield with
unidentified byproducts (entry 10).20 The benzylic alcohol deriva-
tives were not observed. The hydrogenation of 4-acetylnitroben-
zene (2j) quantitatively yielded 4-acetylaniline (3j) (entry 11).
The reaction under 1 atm of H2 at 25 °C with an S/Pd of 1100
was completed in 2 h (TOFav = 550 hꢀ1) (entry 12). The ester and
nitrile functionalities were not injured through the reaction of 2k
THF
14.5
13.5
22
14.5
CH3OH
CH3OH
CH3OH
a
Unless otherwise stated, reactions were conducted at 50 °C using 1.0 mmol of 2
in solvent containing Pd NPs 1b. In all cases, the starting material was completely
consumed (conversion = 100%).
b
Substrate/Pd molar ratio.
Determined by 1H NMR analysis using 1,3,5-trimethoxybenzene as an internal
c
standard. The isolated yield is given in parentheses.
d
Reaction at 30 °C.
e
4-Chlorophenylhydroxyamine (4g) (20%) and 3a (27%) were observed.
Twenty equivalents of TMEDA were added to Pd.
4,40-Dichlorohydrazobenzene (7%) was detected.
Unidentified compounds were produced.
Reaction at 25 °C.
f
g
h
i
and 2l (entries 13 and 14).21 The reaction of 6-nitroquinoline
(2m), a fused heteroaromatic substrate, quantitatively afforded
the aminoquinoline 3m (entry 15). 1,3-Dinitrobenzene (2n) was
completely transformed to the diaminobenzene 3n (entry 16).
The alkenyl moiety was preferentially hydrogenated over the nitro
group in the reaction of 4-(2-methyl-1-propenyl)nitrobenzene.
The hydrogenation of nitroarenes was applied to the one-pot
synthesis of N-arylimines (Scheme 2). The reaction of 2-
methoxynitrobenzene (2d) in toluene under 1 atm of H2 (balloon)
at 50 °C catalyzed by the Pd NPs 1b with an S/Pd of 1000 was com-
pleted in 5 h. Acetophenone was added to this reaction mixture,
which was then heated at 50 °C with a drying agent for 2 days to
afford the imine 5 in 65% isolated yield by distillation.22 The keti-
mine 5 can be enantioselectively hydrogenated with our original
chiral Ru catalyst to give the N-arylamine 6 in 99% ee.23
In summary, Pd NPs stabilized by alkyne derivatives act as
homogeneous catalysts for hydrogenation of nitroarenes to the aryl
amines. The reaction of nitrobenzene proceeds smoothly with an
S/Pd of 51,000 under 8 atm of H2 (TOFav = 1275 hꢀ1) and with an

N. Arai et al. / Tetrahedron Letters 56 (2015) 3913–3915
3915
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chiral Ru cat. = RuBr2[(S,S)-xylskewphos][(S,S)-dpen]
Scheme 2. One-pot Synthesis of an N-Arylketimine 5 from the Nitroarene 2d,
connecting to the synthesis of Chiral N-Arylamine 6.
S/Pd of 1030 under 1 atm of H2 (TOFav = 258 hꢀ1). A series of
nitroarenes with substituents on the aryl rings, including 4-acetyl-
and 4-formylnitrobenzenes, are converted to aryl amines with high
chemoselectivity. The catalytic activity and chemoselectivity of the
Pd NPs are higher than those of the ordinary Pd supported by
charcoal.
Acknowledgments
11. Selected recent publications on the chemoselective reactions with the Ni-
based catalysts: (a) Liu, Y.-C.; Chen, Y.-W. Ind. Eng. Chem. Res. 2006, 45, 2973;
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This work was supported by Grants-in-Aid from the Japan
Society for the Promotion of Science (JSPS) (No. 24350042) and
the MEXT (Japan) program ‘Strategic Molecular and Materials
Chemistry through Innovative Coupling Reactions’ of Hokkaido
University.
12. Selected recent publications on the chemoselective reactions with
miscellaneous metal-based catalysts: (a) Deshpande, R. M.; Mahajan, A. N.;
Diwakar, M. M.; Ozarde, P. S.; Chaudhari, R. V. J. Org. Chem. 2004, 69, 4835; (b)
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Supplementary data
Supplementary data (preparative method of Pd NPs 1b and
NMR spectra of compounds 3) associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.
2015.04.116.
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