Iron-catalyzed selective reduction of nitroarenes to anilines using organosilanes

Article abstract of DOI:10.1039/b924228g

The iron-catalyzed reduction of aromatic nitro compounds to the corresponding anilines applying organosilanes is reported. In the presence of FeX₂-R₃P catalysts a series of nitroarenes is selectively reduced tolerating a wide range of functional groups.

Full text of DOI:10.1039/b924228g

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Iron-catalyzed selective reduction of nitroarenes to anilines
using organosilanes
Kathrin Junge, Bianca Wendt, Nadim Shaikh and Matthias Beller*
Received (in Cambridge, UK) 18th November 2009, Accepted 22nd December 2009
First published as an Advance Article on the web 13th January 2010
DOI: 10.1039/b924228g
The iron-catalyzed reduction of aromatic nitro compounds to the
corresponding anilines applying organosilanes is reported. In the
presence of FeX2–R3P catalysts a series of nitroarenes is
selectively reduced tolerating a wide range of functional groups.
development of a hydrosilylation protocol for nitroarenes.13
Herein, we present the first general method of this type.
Preliminary experiments were carried out with p-nitrobromo-
benzene as model substrate using different iron(II) and iron(III)
precursors, several phosphines, and different silanes in toluene
(Tables 1–3). Obviously, no appreciable reaction takes place
without catalyst (Table 1, entry 20) or silane (Table 1, entry 18),
while in the presence of 10 mol% of simple iron(II) halides
excellent yields (95–98%) of p-bromoaniline are detected
(Table 1, entries 3 and 4). Applying Fe(OAc)2, Fe(acac)2,
Fe(II)stearate, [Fe(CO)5], FeCl3Á6H2O, or Fe(ClO4)3ÁxH2O
the product is also formed but in lower yields (Table 1,
entries 5, 7–9, 15 and 17).
Nitroarenes constitute central building blocks in organic
synthesis.1 Both in industry and academic laboratories, their
reduction serves as an important method for the preparation
of functionalized anilines, which are intermediates for agro-
chemicals, pharmaceuticals, dyes, and pigments.2 Traditional
non-catalytic processes using either Bechamp or sulfide reduction
´
produce a large amount of waste.3 Nowadays, in general
recyclable heterogeneous catalysts are used for the catalytic
hydrogenation of aromatic nitro compounds to anilines.4 In
addition to hydrogen, other reducing agents have been used
for the preparation of anilines.5 Obviously, hydrogenation of a
variety of nitroarenes is well established applying com-
mercially available heterogeneous catalysts. However, some-
times selectivity problems occur and the formation of (toxic)
by-products or impurities is known.6 Due to the easier tuning
and milder reaction conditions homogeneous reduction of
nitro compounds involving catalytic hydrogenation,5,7 transfer
hydrogenation,8 and hydrosilylation has also been studied to
some extent. In order to avoid the necessity to use autoclaves
and/or to handle hydrogen, hydrosilylation offers an attractive
alternative. However, with respect to nitro reduction this
methodology has been largely ignored. Until now, only a
handful of reports for the nitroarene reduction to amines with
silanes has been published focussing on Pd,9a,e–h Pt,9b Rh,9b,c
Sn,9d and Re catalysts.9i Due to the importance of selective
reduction of aromatic nitro compounds, the search for
improved chemoselective methods remains an actual goal.
With respect to catalyst development iron-based complexes
are more and more in the limelight of catalytic applications.10
Due to their abundant availability, most iron compounds are
inexpensive. Often they can be considered as biomimetic and
some of them represent less-toxic alternatives to palladium,
rhodium or ruthenium catalysts.
In the absence of the phosphine, the reactivity is reduced
significantly (Table 1, entry 19). To exclude the possibility of
active copper traces as contaminants of iron salts in the
hydrosilylation reaction, CuBr and CuI were tested directly
as catalyst showing no significant conversion (Table 1, entries
21 and 22).14 Next, we investigated the influence of different
Table 1 Applying different Fe and Cu precursors for the hydrosilylation
of p-nitrobromobenzenea
Entry
Precursor
PR3
Silane
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18b
19c
20d
21
22
FeF2
FeCl2
FeBr2
FeI2
Fe(OAc)2
FeSO4Á7H2O
Fe(acac)2
Fe(II)stearate
[Fe(CO)5]
Fe(III)citrate
Fe2O3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
—
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
—
3
47
95
98
79
4
59
66
68
4
2.5
3
46
19
67
2
Fe3O4
Fe(NO3)3Á9H2O
Fe(BF4)3
FeCl3Á6H2O
FePO4Á4H2O
Fe(ClO4)3ÁxH2O
FeBr2
FeBr2
—
CuBr
CuI
While iron-mediated hydrosilylations of carbonyl com-
pounds have been investigated intensively,11 to the best of
our knowledge only very recently Nagashima and co-workers
observed the reduction of the nitro moiety of a carboxamide
with [Fe3(CO)12] and TMDS.12 Based on our background
in iron-catalyzed reductions we became interested in the
88
6
25
5
6
5
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PCy3
PCy3
PCy3
a
Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock,
¨
¨
Reaction conditions: 1 mmol p-nitrobromobenzene, 0.1 mmol Fe
or Cu precursor, 0.12 mmol PCy3, 2.5 equiv. PhSiH3, 1.5 mL toluene,
Albert-Einstein-Straße 29a, 18059 Rostock, Germany.
E-mail: matthias.beller@catalysis.de; Fax: +49-381-1281-51113;
Tel: +49-381-1281-113
b
c
d
110 1C, 16 h. Without PhSiH3. Without PCy3. Without FeBr2.
ꢀc
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Table 4 FeBr2-catalyzed hydrosilylation of nitroarenes to anilinesa
Table 2 Hydrosilylation of p-nitrobromobenzene: influence of different
phosphinesa
Entry
Substrate
Amine
Yield (%)
1
85
89
42
2
Entry
Precursor
PR3
Yield (%)
3b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
FeBr2
FeI2
PPh3
PPh3
PCy3
(4-MeO-Ph)3P
(4-Me-Ph)3P
(4-F-Ph)3P
(Bn)3P
nBuPAd2
MePPh2
dppethene
dppe
dppb
dpph
dppf
99
30
95
99
97
90
10
97
99
20
28
84
80
14
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
FeBr2
4
99
96
94
91
93
5b
6
7
8
a
9
84
Reaction conditions: 1 mmol p-nitrobromobenzene, 0.1 mmol FeX2,
0.12 mmol phosphine, 2.5 equiv. PhSiH3, 1.5 mL toluene, 110 1C, 16 h.
10
11
12
99
99
72
phosphine ligands on the reduction of the model substrate. We
were pleased to find a quantitative yield of p-bromoaniline by
using a convenient in situ catalyst consisting of FeBr2 and
PPh3 or other arylphosphines (Table 2, entries 1, 4 and 9).
While most of the monodentate phosphines bearing aromatic
or bulky substituents are highly reactive giving product yields
above 90%, chelating phosphines reduce the reaction rate
(Table 2, entries 10–14).
99
71e
13
14
50
99
84
15b
The reduction of p-nitrobromobenzene was also studied in
the presence of different arylsilanes, polymethylhydrosiloxane
(PMHS), trichlorosilane, and alkoxysilanes. Nevertheless, phenyl-
silane remains the reagent of choice leading to quantitative
yield (Table 3, entry 1). While alkoxysilanes showed similar
reactivity (60–66% yield), aryl- or alkylsilanes containing
only one Si–H group gave poorer results. Finally, we were
interested in the functional group tolerance of our protocol.
Hence, 26 different nitro-substituted arenes and heteroarenes
were reacted under the previously optimized reaction con-
ditions (FeBr2, Ph3P, 2.5 equivalents of PhSiH3 in toluene
at 110 1C). The results are summarized in Table 4.15
16
17b,c
83
59
18
19
58e
82
20
77
25
21b
Table 3 Hydrosilylation of p-nitrobromobenzene: influence of different
silanesa
22
61
Entry
Silane
Yield (%)
23
24
80
76
1
2b
3
4
5
6
7
8
9
10
PhSiH3
PhSiH3
Ph2SiH2
Me2PhSiH
Et3SiH
Cl3SiH
PMHS
(EtO)3SiH
Me(EtO)2SiH
(MeO)3SiH
99
78
48
8
9
5
31
66
64
60
25d
26d
40
85
a
Reaction conditions: 1 mmol nitroarene, 0.1 mmol FeBr2, 0.12 mmol
b
PPh3, 2.5 equiv. PhSiH3, 1.5 mL toluene, 110 1C, 16 h. Working up
procedure without MeOH. 2–3% of the diamine were detected.
c
a
Reaction conditions: 1 mmol p-nitrobromobenzene, 0.1 mmol FeBr2,
b
d
e
1% of CQC hydrogenation was detected. Up scaling by factor 5
and isolated yields are given.
0.12 mmol PPh3, 2.5 equiv. silane, 1.5 mL toluene, 110 1C, 16 h. Up
scaling by factor 5 and isolated yield is given.
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Non-substituted nitrobenzene and -toluene are effectively
reduced in 85–89% yield (Table 4, entries 1 and 2). Except
for fluorine substituents, high yields of the corresponding
anilines are achieved in the presence of halide substituents
irrespective of their ring position (Table 4, entries 3–11). Even
3,4,5-trichoro-nitrobenzene produced selectively the respective
aniline in 84% yield (Table 4, entry 9). In none of these cases
significant amounts (>2%) of dehalogenation have been
observed. Notably, other reducible functional groups such as
cyano, nitro, ester groups as well as CQC double bonds
are not affected under these conditions. The reduction of
1,4-dinitrobenzene proceeds chemoselectively affording 83%
of 4-nitroaniline (Table 4, entry 17). The reduction of cyano-
substituted nitrobenzenes, which are important transformations
in organic chemistry, gave 56–82% of cyanoanilines (Table 4,
entries 18 and 19). To our delight the nitro group is highly
chemoselectively reduced in ethyl p-nitrocinnamate and
p-nitrostilbene (Table 4, entries 25 and 26). However, no
aniline was formed in the hydrosilylation of 3-nitrostyrene
and 4-nitrophenylacetate.
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505–509.
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In summary, a new inexpensive and convenient iron-based
catalytic system consisting of FeBr2–Ph3P has been discovered
for the reduction of nitroarenes with organosilanes. The
procedure is general and the selectivity of the catalyst has
been demonstrated applying challenging substrates with
CQO, CRN, CQC, and OH groups.
12 Y. Sunada, H. Kawakami, T. Imaika, Y. Motoyama and
H. Nagashima, Angew. Chem., 2009, 121, 9675–9678.
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9, 5429–5432; (d) S. Enthaler, B. Spilker, G. Erre, K. Junge,
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15 General procedure for the hydrosilylation of nitroarenes:
0.12 mmol (31.5 mg) PPh3, 0.1 mmol (21.6 mg) FeBr2, and 1 mmol
of the corresponding nitroarene are mixed in a pressure tube and
flashed three times with vacuum and argon. Then, 2.5 mmol
PhSiH3 (308 mL) and 1.5 mL dry toluene are added. The mixture
is stirred for 16 hours in a preheated oil bath at 110 1C. After
cooling the pressure tube to room temperature diglyme or
hexadecane are added as internal standard and the mixture is
diluted with 4 mL THF. The reactionis quenched with 2 mL NaOH
(2 N) and stirred for 30 minutes. By adding 4 mL MeOH the two
phases were homogenized. The yield was determined by GC (HP5:
50-8-260/5-8-280/5-8-300). All amines are analyzed by GC–MS
and identified by comparison with authentic primary amines. The
reaction was scaled up by factor 5 for three substrates. The
corresponding amines were isolated and purified by column
chromatography (pentane–ethyl acetate = 5 : 1 - 2 : 1).
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