Indium(III)-Catalyzed Reduction of Nitrobenzenes to Anilines: Scope and Limitations

Article abstract of DOI:10.1055/s-0034-1378850

We have demonstrated that a combination of indium(III) iodide and 1,1,3,3-tetramethyldisiloxane (TMDS) effectively catalyzes the chemoselective reduction of nitrobenzenes with a variety of functional groups (halogens, alkyl, alkoxy, hydroxy, ester, amino, amide, cyanide, thiol, and an alkene moiety), producing the corresponding aniline derivatives.

Full text of DOI:10.1055/s-0034-1378850

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 3179–3185
paper
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N. Sakai et al.
Paper
Synthesis
Indium(III)-Catalyzed Reduction of Nitrobenzenes to Anilines:
Scope and Limitations
Norio Sakai*
NO2
NH2
InI3 (cat.) + TMDS
PhMe, 60 °C
Shun Asama
R
R
Takeo Konakahara
Yohei Ogiwara
22 examples
alkyl, OR, NR2, halogens, CN,
ester, amide, thiol, alkene, etc.
Department of Pure and Applied Chemistry, Faculty of Science
and Technology, Tokyo University of Science (RIKADAI), Noda,
Chiba 278-8510, Japan
chemoselectivity
sakachem@rs.noda.tus.ac.jp
Received: 30.04.2015
Accepted after revision: 18.05.2015
Published online: 15.07.2015
a nitro group on the benzene ring.7 Also, Fernandes and co-
workers reported that the combination of either
ReIO2(PPh3)2 or ReOCl3(PPh3)2 and dimethylphenylsilane
chemoselectively reduces nitrobenzenes, producing the
corresponding anilines.8 Moreover, the facile conversion of
nitrobenzenes into anilines through an iron(II)-catalyzed
reduction in the presence of phenylsilane has been dis-
closed by Beller and co-workers.9
In addition to these reports, as an example of a hetero-
geneous catalytic system using a hydrosilane, Lipowitz and
Bowman have reported that the heterogeneous Pd/C–PMHS
catalytic system reduces aromatic nitro groups.10 Recently,
Park and co-workers found that a magnetically separable
gold nanoparticle catalyst is highly active in the reduction
of a nitro group in the presence of 1,1,3,3-tetramethyldisi-
loxane (TMDS).11
On the basis of these results, we focused on the combi-
nation of an indium(III) compound and a hydrosilane that
displays unique reductive conversions of oxygen- or nitro-
gen-containing functional groups, or organic halides,12,13
and we found that the indium(III) iodide catalyzed deoxy-
genation of nitrobenzenes with TMDS effectively performs
the selective reduction of a nitro group on aromatic nitro
compounds, producing the corresponding anilines.14 How-
ever, the substrates employed in our previous work were
limited to two examples, and the application of chemose-
lectivity as well as the substrate scope remained unex-
plored. Moreover, until now, only a few studies have fo-
cused on the catalytic reduction of substituted nitroben-
zenes using both a main-group metal and a hydrosilane. In
this paper, we reexamine our previous reaction conditions,
and with the optimal indium compound and the hydrosi-
lane in hand, we report the scope and limitations of the re-
ductive conversion of nitrobenzenes that contain a variety
of functional groups.
DOI: 10.1055/s-0034-1378850; Art ID: ss-2015-f0275-op
Abstract We have demonstrated that a combination of indium(III) io-
dide and 1,1,3,3-tetramethyldisiloxane (TMDS) effectively catalyzes the
chemoselective reduction of nitrobenzenes with a variety of functional
groups (halogens, alkyl, alkoxy, hydroxy, ester, amino, amide, cyanide,
thiol, and an alkene moiety), producing the corresponding aniline de-
rivatives.
Key words indium, reduction, hydrosiloxanes, nitrobenzenes, anilines
The reductive conversion of nitrobenzenes into anilines
has attracted major interest in organic and pharmaceutical
chemistry from the viewpoints of the facile availability of
the starting nitro compounds, the easy handling on a labo-
ratory scale, and the production of a skeleton that can sup-
ply a material source of biologically active substances and
functional materials.1 To minimize the formation of by-
products that arise from side reactions that lead to undesir-
able functional groups, recent efforts have focused on the
development of effective procedures that display high che-
moselectivity toward only a nitro group. For instance,
during the past decade, to address this subject, a number of
heterogeneous catalytic systems composed of either a tran-
sition metal charcoal or a catalyst support and a reducing
reagent, such as hydrazine,2 sodium borohydride,3 ammo-
nia–borane complex,4 potassium hydroxide (as a hydride
source),5 and hydrogen gas,6 have been developed.
In a parallel development, several homogeneous cata-
lytic systems that combine a transition metal and a milder
reducing source, a hydrosilane, have been shown to effec-
tively undertake the reductive conversion of nitrobenzenes
into anilines. For example, Rahaim and Maleczka found that
a palladium(II) acetate–polymethylhydrosiloxane (PMHS)
system in the presence of potassium fluoride could reduce
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Table 1 Examination of the Reaction Conditionsa
InX3
O
N
H
silane
Ph NO2
N
Ph
+
N
Ph
+
+
Ph NH2
Ph
N
Ph
N
Ph
solvent
H
Ph
N
1a
1b
1c
1d
Entry
InX3
Hydrosilane (equiv)
Solvent
Yieldb (%)
1a
1b
1c
1d
1
2
3
4
5
6
7
8
InBr3
Et3SiH
PhSiH3
TMDS
PhSiH3
TMDS
TMDS
TMDS
TMDS
(4)
(4)
(4)
(4)
(4)
(4)
(4)
(6)
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
DCEc
17
45
37
29
72
81
78
90d
0
0
8
74
7
InBr3
InBr3
InI3
trace
trace
trace
8
0
5
4
2
6
trace
0
InI3
4
3
2
1
5
InI3
7
InI3
toluene
toluene
2
InI3
3
a Reaction conditions: catalyst (5 mol%), hydrosilane (Si-H: 4–6 equiv), 60 °C, 4 h.
b GC yield.
c 1,2-Dichloroethane.
d Isolated yield.
On the basis of our previous study,14 when nitrobenzene
was initially treated with indium(III) bromide (5 mol%) and
triethylsilane (4 equiv) in chloroform at 60 °C for four
hours, the expected aniline (1a) was obtained in only a 17%
yield, whereas hydrazobenzene (1d) was produced as the
major product (Table 1, entry 1). The use of phenylsilane or
TMDS instead of triethylsilane led to an improvement in the
yield of aniline (1a), with the formation of trace amounts of
azoxybenzene (1b) and azobenzene (1c) (Table 1, entries 2
and 3). When nitrobenzene was treated with a combination
of indium(III) iodide and phenylsilane, however, the yield of
aniline was slightly decreased (Table 1, entry 4). In contrast,
the use of indium(III) iodide and TMDS drastically im-
proved both the reactivity and the selectivity (Table 1, en-
try 5). As a solvent effect, both 1,2-dichloroethane (DCE)
and toluene also provided a large positive effect in this re-
duction (Table 1, entries 6 and 7). In particular, when the
treatment of nitrobenzene was conducted with a reducing
system involving indium(III) iodide (5 mol%) and TMDS (6
equiv) in toluene at 60 °C, the reductive conversion pro-
ceeded smoothly to give aniline (1a) in the best yield (Table
1, entry 8). Under the best conditions, the resulting aniline
was easily isolated from byproduct impurities via simple
silica gel chromatography.
group, such as a methyl group, were reduced smoothly, pro-
ducing the corresponding aniline derivatives 2a–4a in good
yields (Table 2, entries 1–3); the position of the methyl sub-
stituent had no significant effect on the yield. In contrast, a
strong electron-donating group, such as an unsubstituted
amino group, hindered the reduction and resulted in a de-
creased product yield, although a dimethylamino group
produced aniline derivative 6a in a relatively good yield (Ta-
ble 2, entries 4 and 5). In a similar manner, the use of a ni-
trobenzene derivative with an oxygen-containing electron-
donating group, such as a hydroxy or a methoxy group, gave
aniline derivatives 7a and 8a, respectively, in remarkably
low yields (Table 2, entries 6 and 7), similar to our previous
conversions using an indium(III)/hydrosilane reducing sys-
tem.13 This result implies that the electronic effect of such
groups decreases the electrophilicity of the nitro group,
which leads to a restraint in the reduction. In contrast, re-
gardless of the substitution position, nitrobenzenes with
electron-withdrawing groups, such as a trifluoromethyl
group or a halogen, were effectively reduced to produce the
corresponding aniline derivatives 9a–14a in satisfactory
yields (Table 2, entries 8–13). Also, when the reaction was
conducted with a disubstituted nitrobenzene containing
both a fluoride and a methyl group, or with 1-nitronaph-
thalene, the corresponding aniline derivative 15a and 1-
aminonaphthalene (16a) were obtained in 74% and 53%
yield, respectively (Table 2, entries 14 and 15).
Under the optimal conditions, the generality of this re-
duction was examined using a variety of mono- and disub-
stituted nitrobenzenes, and the results are listed in Table 2.
For instance, nitrobenzenes with a weak electron-donating
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Table 2 (continued)
Table 2 Reductive Conversion of Nitrobenzene Derivatives into Aniline
Derivatives
Entry
Product
Time (h)
6
Yielda (%)
68
NH2
InI3 (5 mol%)
TMDS (Si-H: 6 equiv)
13
14a
NH2
NO2
I
R
R
PhMe, 60 °C
F
NH2
14
15
15a
16a
6
74
53
Entry
Product
Time (h)
4
Yielda (%)
82
Me
NH2
NH2
1
2
2a
3a
12
Me
NH2
a Isolated yield.
b 1,2-Dichloroethane was used as the solvent.
4
78
Me
NH2
To expand the scope and chemoselectivity of this reduc-
3
4a
5a
4
80
48
ing system to access other aniline derivatives, the reduction
of a variety of alternative aromatic nitro compounds was
investigated (Scheme 1). For instance, when nitrobenzenes
with a linear or a cyclic ester moiety derived from benzoic
acid were treated under the optimal conditions, the present
catalytic system had an effect on only the nitro group, and
produced the corresponding anilines 17a and 18a in good
yields. In contrast, the use of nitrobenzenes with a carbox-
ylic acid or an acetal moiety did not give the corresponding
aniline derivatives 19a and 20a. When the reduction was
Me
NH2
4b
10
H2N
NH2
5
6
7
8
9
6a
6
8
8
8
4
69
25
20
67
72
Me2N
NH2
7a
HO
InI3 (5 mol%)
TMDS (Si-H: 6 equiv)
NO2
NH2
NH2
NH2
R
R
PhMe, 60 °C
8a
MeO
F3C
O
NH2
NH2
NH2
9a
MeO
HO
O
O
O
19a: 0% (8 h)
NH2
NH2
17a: 81% (4 h)
18a: 75% (4 h)
10a
Cl
NH2
NH2
O
NH2
MeO
NC
Ph
N
10
11a
4
68
H
OMe
Cl
20a: 0% (4 h)
21a: 74% (4 h)
22a: 0% (4 h)
NH2
NH2
NH2
NH2
11
12
12a
13a
4
8
74
63
O
Cl
N
H
HS
NH2
I
CN
23a: 53% (4 h)
24a: 16% (4 h)
25a: 77% (6 h)
Scheme 1 Scope and limitations of the chemoselective reduction of
nitrobenzene derivatives (isolated yields shown)
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N. Sakai et al.
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carried out using a nitrobenzene with an amide functional-
ity, the catalytic system responded to only the nitro group,
producing the expected aniline 21a in a good yield. It is odd
that p-cyanonitrobenzene, which has the cyano group di-
rectly bonded to the benzene ring, was not reduced to the
corresponding aniline 22a, but the nitrobenzene embedded
with a methylene chain between the benzene ring and the
cyano group was reduced to the expected aniline derivative
23a in a moderate yield. The use of 4-nitrothiophenol af-
forded the aniline derivative 24a in a low yield. Both the
terminal alkene and the amide moiety remained intact af-
ter our reductive treatment of N-(4-nitrophenyl)-10-unde-
cenamide, which provided 25a in 77% yield.
On the basis of the results of the control experiments,
we propose a plausible mechanism for the reduction of ni-
trobenzenes (Scheme 3). Initially, nitrobenzene A that is ac-
tivated by the indium compound is reduced by a hydrosi-
lane, forming nitrosobenzene B as a key intermediate with
the elimination of a silanol. Then, the activated nitrosoben-
zene is reduced twice, finally producing aniline C with the
liberation of a siloxane. Although the relationship between
the type of hydrosilane and the reaction mechanism is not
clear at this stage, among hydrosilanes, a relatively weak re-
ducing reagent, namely a siloxane such as TMDS, displays a
large effect.16 On the other hand, the use of a relatively
strong hydrosilane, such as phenylsilane, results in a de-
creased yield of aniline.
Several control experiments were conducted to clarify
the reaction path for this reduction of nitrobenzenes. When
nitrosobenzene was treated under the optimal conditions
involving TMDS (Si-H: 3 equiv), the reduction was complet-
ed within 1 hour to produce aniline (1a) in a 90% GC yield
(Scheme 2, eq 1). Further, when nitrosobenzene was treat-
ed with only TMDS in the absence of indium(III) iodide, for-
mation of the expected aniline was not observed, rather a
24% GC yield of azoxybenzene (1b) was obtained (Scheme
2, eq 2). Both results imply that the activation with the in-
dium compound hinders the formation of azoxybenzene
via the dimerization of nitrosobenzene, and effectively pro-
motes the reduction of the nitroso compound as a mono-
mer. Treatment of hydrazobenzene (1d) under the optimal
conditions did not afford aniline (1a), hence proving that an
aniline derivative is not formed through decomposition of
the corresponding hydrazobenzene (Scheme 2, eq 3). More-
over, when the UV–vis spectrum of the toluene solution
(1.0 × 10–2 M) involving nitrobenzene (0.1 mmol), indi-
um(III) iodide (0.1 equiv for nitrobenzene), and TMDS (Si-
H: 6 equiv for nitrobenzene) was measured, a broad absorp-
tion attributable to nitrosobenzene was observed at 386
nm (see Figure 1 in the Supporting Information).15 This ab-
sorption gradually disappeared over time, being replaced
by two absorptions derived from aniline at 232 and 278
nm.
[In]
[In]
[In]
O
+
O
+
O–
Si
Si-H
O
O
Si
Ar
N
Ar
N
Ar
N
– Si-OH
O
H
H
A
[In]
Si-H
OSi
O
[In]
Si-H
Ar NH2
Ar
N
Ar
N
–
Si-OSi
H
B
C
Scheme 3 Plausible mechanism for the reduction of nitrobenzenes
In conclusion, we have demonstrated an indium(III)-
catalyzed reductive conversion of nitrobenzenes into ani-
line derivatives. In particular, we have found that the pres-
ent reducing system, which is composed of indium(III) io-
dide and 1,1,3,3-tetramethyldisiloxane in toluene, shows a
high tolerance to a variety of functional groups, such as hal-
ogens, ester, amide, cyanide, thiol, and an alkene moiety,
groups which are sensitive to common reducing reagents
and strong acid conditions. We have also established that
the reduction process proceeds via a nitrosobenzene inter-
mediate.
All reactions were carried out under a N2 atmosphere, unless other-
wise noted. Toluene was freshly distilled from sodium/benzophenone
prior to use. All indium salts and nitrobenzenes are commercially
available, and were used without further purification. Hydrosilanes
were also used without further purification. Reactions were moni-
tored via TLC analysis of reaction aliquots. TLC was performed on sili-
ca gel 60 F254, and the components were located by observation under
UV light. GC yields were determined using the standard curve of dec-
ane as an internal standard. Column chromatography was performed
using silica gel. 1H NMR spectra were measured at 500 (or 300) MHz
using tetramethylsilane as an internal standard. 13C NMR spectra
were measured at 125 (or 75) MHz using the center peak of chloro-
form (77.0 ppm) as an internal standard. Mass spectra were mea-
sured using a JEOL GCMate (electron impact) mass spectrometer. 4-
(Dimethoxymethyl)nitrobenzene,17 4′-nitrobenzanilide,18 and N-(4-
nitrophenyl)-10-undecenamide19 were prepared according to litera-
ture methods, and their spectra agreed with the reported data. Data
InI3 (5 mol%)
TMDS (Si-H: 3 equiv)
(1)
(2)
Ph NO
Ph NO
Ph NH2
1a: 90% (GC)
O
PhMe, 60 °C, 1 h
TMDS (Si-H: 3 equiv)
N
Ph
PhMe, 60 °C, 4 h
Ph
N
1b: 24% (GC)
InI3 (5 mol%)
TMDS (Si-H: 3 equiv)
H
N
Ph
(3)
Ph
N
NR
H
PhMe, 60 °C, 4 h
1d
Scheme 2 Control experiments to clarify the reaction mechanism
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for the byproducts, azoxybenzene (1b), azobenzene (1c), and hydra-
zobenzene (1d), also agreed with the literature spectra characteriza-
tions.13f
N,N-Dimethyl-1,4-phenylenediamine (6a)21
Yield: 56 mg (69%); black solid; mp 33.5–36.9 °C.
1H NMR (300 MHz, CDCl3): δ = 2.81 (s, 6 H), 3.33 (s, 2 H), 6.62–6.70
(m, 4 H).
Reductive Conversion of Nitrobenzenes into Anilines; General
Procedure
13C NMR (75 MHz, CDCl3): δ = 42.0, 115.5, 116.4, 137.8, 144.7.
MS (EI): m/z (%) = 137 (100) [M+ + H].
To a screw top vial (5 mL) under N2 containing freshly distilled tolu-
ene (0.6 mL) were successively added an aromatic nitro compound
(0.60 mmol), InI3 (14.9 mg, 0.030 mmol), and TMDS (318 μL, 1.80
mmol). After the vial was sealed with a cap that contained a PTFE
septum, the mixture was stirred at 60 °C (bath temperature), and
monitored via TLC analysis. Sat. aq NaHCO3 solution (5 mL) was added
to the resultant mixture, which was then extracted with EtOAc (3 × 6
mL). The combined organic phases were dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. The crude
product was purified by silica gel column chromatography (n-hex-
ane–EtOAc, 9:1 to 4:1) to afford the corresponding aniline derivative.
p-Aminophenol (7a)20
Yield: 16 mg (25%); gray powder; mp 189.4–190.2 °C.
1H NMR (500 MHz, DMSO-d6): δ = 4.40 (s, 2 H), 6.42 (d, J = 8.5 Hz, 2
H), 6.48 (d, J = 8.5 Hz, 2 H), 8.37 (s, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 115.4, 115.6, 140.6, 148.3.
MS (EI): m/z (%) = 109 (100) [M+].
p-Anisidine (8a)20
Yield: 15 mg (20%); brown solid; mp 55.7–57.5 °C.
1H NMR (300 MHz, CDCl3): δ = 3.42 (s, 2 H), 3.73 (s, 3 H), 6.62 (d,
J = 6.5 Hz, 2 H), 6.73 (d, J = 6.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 55.6, 114.7, 116.3, 139.9, 152.7.
MS (EI): m/z (%) = 123 (35) [M+], 108 (100) [M+ – Me].
Aniline (1a)20
Yield: 52 mg (90%); colorless liquid.
1H NMR (300 MHz, CDCl3): δ = 3.55 (s, 2 H), 6.65 (d, J = 7.4 Hz, 2 H),
6.73 (d, J = 7.4 Hz, 1 H), 7.16 (d, J = 7.4 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 115.0, 118.4, 129.2, 146.3.
MS (EI): m/z (%) = 94 (100) [M+ + H].
4-(Trifluoromethyl)aniline (9a)22
Yield: 65 mg (67%); yellow liquid.
1H NMR (500 MHz, CDCl3): δ = 3.90 (s, 2 H), 6.63 (d, J = 8.2 Hz, 2 H),
7.36 (d, J = 8.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 114.1, 119.3 (q, JC-F = 32.3 Hz), 124.9
(q, JC-F = 270.3 Hz), 126.6 (d, JC-F = 3.8 Hz), 149.4.
MS (EI): m/z (%) = 162 (100) [M+ + H].
o-Toluidine (2a)20
Yield: 54 mg (82%); light yellow liquid.
1H NMR (500 MHz, CDCl3): δ = 2.23 (s, 3 H), 3.49 (s, 2 H), 6.34 (d,
J = 7.3 Hz, 2 H), 6.55 (d, J = 7.3 Hz, 1 H), 7.01 (d, J = 7.3 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 21.2, 112.1, 115.7, 119.2, 129.0, 138.9,
146.2.
MS (EI): m/z (%) = 107 (100) [M+].
2-Chloroaniline (10a)23
Yield: 55 mg (72%); yellow liquid.
1H NMR (300 MHz, CDCl3): δ = 3.93 (s, 2 H), 6.29–6.72 (m, 2 H), 7.02
(t, J = 7.8 Hz, 1 H), 7.21 (d, J = 7.8 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 115.8, 118.9, 119.1, 127.5, 129.3, 142.8.
MS (EI): m/z (%) = 127 (100) [M+], 129 (30) [M++ 2].
m-Toluidine (3a)20
Yield: 50 mg (78%); yellow liquid.
1H NMR (300 MHz, CDCl3): δ = 2.21 (s, 3 H), 3.49 (s, 2 H), 6.40 (s, 2 H),
6.54 (d, J = 7.3 Hz, 1 H), 7.00 (t, J = 7.3 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 21.1, 112.0, 115.6, 119.0, 128.9, 138.7,
146.2.
3-Chloroaniline (11a)23
MS (EI): m/z (%) = 107 (100) [M+].
Yield: 52 mg (68%); yellow liquid.
1H NMR (500 MHz, CDCl3): δ = 3.64 (s, 2 H), 6.46 (d, J = 7.8 Hz, 1 H),
6.59 (s, 1 H), 6.68 (d, J = 7.8 Hz, 1 H), 7.01 (d, J = 7.8 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 113.0, 114.6, 118.1, 130.2, 134.5,
p-Toluidine (4a)20
Yield: 51 mg (80%); brown solid; mp 41.1–44.0 °C.
1H NMR (500 MHz, CDCl3): δ = 2.23 (s, 3 H), 3.46 (s, 2 H), 6.59 (d,
J = 7.8 Hz, 2 H), 6.95 (d, J = 7.8 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 20.4, 115.2, 127.7, 129.7, 143.7.
MS (EI): m/z (%) = 107 (100) [M+].
147.5.
MS (EI): m/z (%) = 127 (100) [M+], 129 (26) [M++ 2].
4-Chloroaniline (12a)3
Yield: 56 mg (74%); yellow solid; mp 68.2–70.4 °C.
1H NMR (300 MHz, CDCl3): δ = 3.58 (s, 2 H), 6.59 (d, J = 8.9 Hz, 2 H),
7.09 (d, J = 8.9 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 116.2, 123.0, 129.0, 144.9.
MS (EI): m/z (%) = 127 (100) [M+], 129 (28) [M++ 2].
1,4-Phenylenediamine (5a)20
Yield: 31 mg (48%); light brown solid; mp 140.2–142.5 °C.
1H NMR (300 MHz, CDCl3): δ = 3.33 (s, 4 H), 6.57 (s, 4 H).
13C NMR (75 MHz, CDCl3): δ = 116.7, 138.6.
MS (EI): m/z (%) = 109 (100) [M+ + H].
2-Iodoaniline (13a)24
Yield: 83 mg (63%); yellow solid; mp 55.4–58.1 °C.
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1H NMR (500 MHz, CDCl3): δ = 4.03 (s, 2 H), 6.45 (t, J = 6.9 Hz, 1 H),
6.70 (d, J = 6.9 Hz, 1 H), 7.11 (t, J = 6.9 Hz, 1 H), 7.61 (d, J = 6.9 Hz, 1 H).
1H NMR (500 MHz, CDCl3): δ = 3.52 (s, 2 H), 3.77 (s, 2 H), 6.59 (d,
J = 8.0 Hz, 2 H), 7.00 (d, J = 8.0 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 84.1, 114.6, 119.8, 129.8, 138.8, 146.6.
MS (EI): m/z (%) = 219 (100) [M+].
13C NMR (125 MHz, CDCl3): δ = 22.2, 115.0, 118.6, 128.5 (2 C), 146.1.
MS (EI): m/z (%) = 132 (100) [M+].
4-Iodoaniline (14a)23
4-Aminothiophenol (24a)29
Yield: 89 mg (68%); brown solid; mp 61.4–63.1 °C.
Yield: 12 mg (16%); yellow solid; mp 35.0–38.5 °C.
1H NMR (500 MHz, CDCl3): δ = 3.66 (s, 2 H), 6.46 (d, J = 8.2 Hz, 2 H),
7.40 (d, J = 8.2 Hz, 2 H).
1H NMR (500 MHz, CDCl3): δ = 3.73 (s, 2 H), 6.55 (d, J = 7.8 Hz, 2 H),
7.24 (d, J = 7.8 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 79.3, 117.2, 137.9, 146.0.
MS (EI): m/z (%) = 220 (100) [M+ + H], 219 (8) [M+].
13C NMR (125 MHz, CDCl3): δ = 115.3, 125.4, 133.9, 147.1.
MS (EI): m/z (%) = 126 (100) [M+ + H].
3-Fluoro-4-methylaniline (15a)25
N-(4-Aminophenyl)-10-undecenamide (25a)19
Yield: 56 mg (74%); yellow solid; mp 28.5–31.0 °C.
Yield: 127 mg (77%); beige solid; mp 234.6–235.2 °C.
1H NMR (300 MHz, CDCl3): δ = 2.13 (d, J = 1.8 Hz, 3 H), 3.56 (s, 2 H),
6.32–6.36 (m, 2 H), 7.94 (t, J = 8.2 Hz, 1 H).
1H NMR (500 MHz, CDCl3): δ = 1.30–1.36 (m, 10 H), 1.71 (quintet,
J = 7.0 Hz, 2 H), 2.04 (q, J = 7.0 Hz, 2 H), 2.30 (t, J = 7.0 Hz, 2 H), 4.96
(dd, J = 17.0, 10.0 Hz, 1 H), 5.81 (sextet, 1 H), 6.64 (d, J = 8.0 Hz, 2 H),
7.01 (s, 1 H), 7.26 (d, J = 8.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.6 (d, JC-F = 3.1 Hz), 102.1 (d, JC-F
25.3 Hz), 110.6 (d, JC-F = 2.5 Hz), 114.0 (d, JC-F = 17.3 Hz), 131.7 (d, JC-F
6.8 Hz), 145.8 (d, JC-F = 10.5 Hz), 161.8 (d, JC-F = 242.7 Hz).
=
=
13C NMR (125 MHz, CDCl3): δ = 25.7, 28.8, 29.0, 29.2, 29.3, 33.7, 37.4,
114.1, 115.3, 122.0, 129.3, 139.1, 143.1, 171.4.
MS (FAB): m/z (%) = 275 (100) [M+ + H], 274 (7) [M+].
MS (EI): m/z (%) = 126 (100) [M+ + H], 125 (18) [M+].
1-Naphthylamine (16a)21
Yield: 46 mg (53%); colorless needles; mp 45.5–49.0 °C.
1H NMR (300 MHz, CDCl3): δ = 3.86 (s, 2 H), 6.58 (d, J = 6.7 Hz, 2 H),
Acknowledgment
7.11–7.32 (m, 4 H), 7.60–7.67 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 109.6, 118.8, 120.7, 123.5, 124.7, 125.7,
126.3, 128.4, 134.3, 142.0.
MS (EI): m/z (%) = 143 (100) [M+].
This work was partially supported by a Grant-in-Aid for Scientific Re-
search (C) (No. 25410120) from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT). We deeply thank Shin-Etsu
Chemical Co., Ltd. for the gift of hydrosilanes.
Methyl 4-Aminobenzoate (17a)20
Supporting Information
Yield: 73 mg (81%); white solid; mp 109.9–112.3 °C.
1H NMR (500 MHz, CDCl3): δ = 3.85 (s, 3 H), 4.08 (s, 2 H), 6.64 (d,
J = 8.7 Hz, 2 H), 7.85 (d, J = 8.7 Hz, 2 H).
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1378850.
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13C NMR (125 MHz, CDCl3): δ = 51.6, 113.7, 119.6, 131.5, 150.8, 167.1.
MS (EI): m/z (%) = 151 (13) [M+], 120 (100) [M+ – (Me + NH2)].
References
6-Aminophthalide (18a)26
(1) Larock, R. C. Comprehensive Organic Transformations, 2nd ed.;
John Wiley & Sons: New York, 1999, 821–82; and references
cited therein.
Yield: 67 mg (75%); white powder; mp 182.5–184.1 °C.
1H NMR (500 MHz, CDCl3): δ = 3.90 (s, 2 H), 5.15 (s, 2 H), 6.92 (d,
J = 6.9 Hz, 1 H), 7.07 (s, 1 H), 7.18 (d, J = 6.9 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 69.6, 109.8, 121.6, 122.7, 126.9, 136.3,
147.5, 171.5.
(2) For selected recent papers, see: (a) Shi, Q.; Lu, R.; Lu, L.; Fu, X.;
Zhao, D. Adv. Synth. Catal. 2007, 349, 1877. (b) Huang, L.; Luo, P.;
Pei, W.; Liu, X.; Wang, Y.; Wang, J.; Xing, W.; Huang, J. Adv.
Synth. Catal. 2012, 354, 2689. (c) Sharma, U.; Kumar, N.; Verma,
P. K.; Kumar, V.; Singh, B. Green Chem. 2012, 14, 2289. (d) Guha,
N. R.; Bhattacherjee, D.; Das, P. Tetrahedron Lett. 2014, 55, 2912.
(3) For selected recent papers, see: (a) Zhang, F.; Jin, J.; Zhong, X.;
Li, S.; Niu, J.; Li, R.; Ma, J. Green Chem. 2011, 13, 1238. (b) Shil, A.
K.; Sharma, D.; Guha, N. R.; Das, P. Tetrahedron Lett. 2012, 53,
4858. (c) Li, L.; Chen, Z.; Zhong, H.; Wang, R. Chem. Eur. J. 2014,
20, 3050. (d) MacNair, A. J.; Tran, M.-M.; Nelson, J. E.; Sloan, G.
U.; Ironmonger, A.; Thomas, S. P. Org. Biomol. Chem. 2014, 12,
5082.
MS (EI): m/z (%) = 150 (100) [M+ + H].
4′-Aminobenzanilide (21a)27
Yield: 94 mg (74%); white solid; mp 127.2–130.5 °C.
1H NMR (300 MHz, DMSO-d6): δ = 5.21 (s, 2 H), 6.58 (d, J = 8.7 Hz, 2
H), 7.40–7.50 (m, 5 H), 7.93 (d, J = 5.8 Hz, 2 H), 9.99 (s, 1 H).
13C NMR (75 MHz, DMSO-d6): δ = 114.1, 122.3, 127.5, 128.3, 128.6,
131.2, 135.3, 144.6, 164.8.
(4) For a selected recent paper, see: Vasilikogiannaki, E.; Gryparis,
C.; Kotzabasaki, V.; Lykakis, I. N.; Stratakis, M. Adv. Synth. Catal.
2013, 355, 907.
(5) For a selected recent paper, see: Kim, J. H.; Park, J. H.; Chung, Y.
K.; Park, K. H. Adv. Synth. Catal. 2012, 354, 2412.
MS (EI): m/z (%) = 213 (100) [M+ + H].
4-Aminobenzyl Cyanide (23a)28
Yield: 42 mg (53%); light brown powder; mp 45.2–48.9 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 3179–3185

3185
N. Sakai et al.
Paper
Synthesis
(6) For a selected recent paper, see:Reis, P. M.; Royo, B. Tetrahedron
Lett. 2009, 50, 949.
(7) Rahaim, R. J.; Maleczka, R. E. Jr. Org. Lett. 2005, 7, 5087.
(8) de Noronha, R. G.; Romão, C. C.; Fernandes, A. C. J. Org. Chem.
2009, 74, 6960.
(f) Sakai, N.; Asama, S.; Anai, S.; Konakahara, T. Tetrahedron
2014, 70, 2027. (g) Sakai, N.; Matsushita, Y.; Konakahara, T.;
Ogiwara, Y.; Hirano, K. Eur. J. Org. Chem. 2015, 1591.
(14) Sakai, N.; Fujii, K.; Nabeshima, S.; Ikeda, R.; Konakahara, T.
Chem. Commun. 2010, 46, 3173.
(9) Junge, K.; Wendt, B.; Shaikh, N.; Beller, M. Chem. Commun. 2010,
46, 1769.
(15) This UV–vis absorption was slightly red-shifted relative to that
(363 nm) of a solution of only PhNO (toluene, 3.3 × 10–2 M).
(16) Addis, D.; Das, S.; Junge, K.; Beller, M. Angew. Chem. Int. Ed.
2011, 50, 6004.
(17) Kubczyk, T. M.; Williams, S. M.; Kean, J. R.; Davies, T. E.; Taylor,
S. H.; Graham, A. E. Green Chem. 2011, 13, 2320.
(18) Liang, J.; Lv, J.; Shang, Z.-c. Tetrahedron 2011, 67, 8532.
(19) Shirley, D. A.; Schmidt, G. A.; Brown, M. L.; Reedy, W. H. J. Org.
Chem. 1952, 17, 193.
(20) Li, Z.; Li, J.; Liu, J.; Zhao, Z.; Xia, C.; Li, F. ChemCatChem 2014, 6,
1333.
(21) Tao, C.-Z.; Li, J.; Fu, Y.; Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2008,
49, 70.
(10) Lipowitz, J.; Bowman, S. A. J. Org. Chem. 1973, 38, 162.
(11) Park, S.; Lee, I. S.; Park, J. Org. Biomol. Chem. 2013, 11, 395.
(12) For selected reviews or papers on reductive functional group
interconversions with an indium compound and a hydrosilane,
see: (a) Baba, A.; Shibata, I. Chem. Rec. 2005, 5, 323; and refer-
ences cited therein. (b) Yasuda, M.; Onishi, Y.; Ueba, M.; Miyai,
T.; Baba, A. J. Org. Chem. 2001, 66, 7741. (c) Onishi, Y.; Ogawa,
D.; Yasuda, M.; Baba, A. J. Am. Chem. Soc. 2002, 124, 13690.
(d) Miura, K.; Yamada, Y.; Tomita, M.; Hosomi, A. Synlett 2004,
1985. (e) Miura, K.; Tomita, M.; Yamada, Y.; Hosomi, A. J. Org.
Chem. 2007, 72, 787. (f) Tsuchimoto, T.; Wagatsuma, T.; Aoki, K.;
Shimotori, J. Org. Lett. 2009, 11, 2129. (g) Pehlivan, L.; Métay, E.;
Delbrayelle, D.; Mignani, G.; Lemaire, M. Eur. J. Org. Chem. 2012,
4689.
(22) Samant, B. S.; Kabalka, G. W. Chem. Commun. 2011, 47, 7236.
(23) Takasaki, M.; Motoyama, Y.; Higashi, K.; Yoon, S.-H.; Mochida, I.;
Nagashima, H. Org. Lett. 2008, 10, 1601.
(13) (a) Sakai, N.; Moriya, T.; Konakahara, T. J. Org. Chem. 2007, 72,
5920. (b) Sakai, N.; Fujii, K.; Konakahara, T. Tetrahedron Lett.
2008, 49, 6873. (c) Sakai, N.; Usui, Y.; Ikeda, R.; Konakahara, T.
Adv. Synth. Catal. 2011, 353, 3397. (d) Sakai, N.; Miyazaki, T.;
Sakamoto, T.; Yatsuda, T.; Moriya, T.; Ikeda, R.; Konakahara, T.
Org. Lett. 2012, 14, 4366. (e) Moriya, T.; Yoneda, S.; Kawana, K.;
Ikeda, R.; Konakahara, T.; Sakai, N. J. Org. Chem. 2013, 78, 10642.
(24) Ahammed, S.; Saha, A.; Ranu, B. C. J. Org. Chem. 2011, 76, 7235.
(25) Lundgren, R. J.; Peters, B. D.; Alsabeh, P. G.; Stradiotto, M. Angew.
Chem. Int. Ed. 2010, 49, 4071.
(26) Wang, J.; Johnson, D. M. Polym. Int. 2009, 58, 1234.
(27) Wu, X.; Hu, L. J. Org. Chem. 2007, 72, 765.
(28) Velcicky, J.; Soicke, A.; Steiner, R.; Schmalz, H.-G. J. Am. Chem.
Soc. 2011, 133, 6948.
(29) Xu, H.-J.; Liang, Y.-F.; Cai, Z.-Y.; Qi, H.-X.; Yang, C.-Y.; Feng, Y.-S.
J. Org. Chem. 2011, 76, 2296.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 3179–3185