Convenient reduction of nitrobenzenes to anilines using electrochemically generated nickel

Article abstract of DOI:10.1021/jo981935p

The reduction of nitrobenzenes with electrogenerated nickel in DMF gave anilines without affecting the alkenyl, alkynyl, halo, acetyl, methoxy, cyano, ethoxycarbonyl, formyl, benzyloxy, and phenylsulfonylamino groups at room temperature in a short time. The nickel was easily prepared by electrolysis in 0.3 M Et₄NBF₄-DMF solution under an argon atmosphere at a constant current (10 mA/cm²) and can be stored under argon at -20 °C for at least a week. The reduction of nitrobenzenes with electrogenerated nickel in DMF gave anilines without affecting the alkenyl, alkynyl, halo, acetyl, methoxy, cyano, ethoxycarbonyl, formyl, benzyloxy, and phenylsulfonylamino groups at room temperature in a short time. The nickel was easily prepared by electrolysis in 0.3 M Et₄NBF₄-DMF solution under an argon atmosphere at a constant current (10 mA/cm²) and can be stored under argon at -20 °C for at least a week.

Full text of DOI:10.1021/jo981935p

J . Org. Chem. 1999, 64, 2301-2303
2301
Con ven ien t Red u ction of Nitr oben zen es to An ilin es Usin g
Electr och em ica lly Gen er a ted Nick el
Akito Yasuhara,* Atsushi Kasano, and Takao Sakamoto*
Faculty of Pharmaceutical Sciences, Tohoku University, Aobaku, Sendai 980-8578, J apan
Received September 23, 1998
The reduction of nitrobenzenes with electrogenerated nickel in DMF gave anilines without affecting
the alkenyl, alkynyl, halo, acetyl, methoxy, cyano, ethoxycarbonyl, formyl, benzyloxy, and
phenylsulfonylamino groups at room temperature in a short time. The nickel was easily prepared
by electrolysis in 0.3 M Et4NBF4-DMF solution under an argon atmosphere at a constant current
(10 mA/cm2) and can be stored under argon at -20 °C for at least a week.
In tr od u ction
Selective reduction of nitrobenzenes to the correspond-
ing anilines is of importance in synthetic organic chem-
istry. Generally, catalytic reductions with some metals
(e.g., Raney nickel,1a,d Pd-C,1d PtO21a) and a mixture of
metal (e.g., Fe,1b Sn,1a,b and SnCl21b,c) and HCl have been
used. However, these methods are not selective and may
affect functional groups such as iodo, benzyloxy, and
formyl. Therefore, many other methods have been re-
ported.2 For example, the combination of hydrazine and
metal (e.g., Raney nickel,3 Pd-C,1d graphite4), NaBH4 and
metal (e.g., Pd-C,5 Pt-C,6 and CoCl2-C7), and RuCl2-
(PPh3)2-H2.8 Each method has its own advantages and
disadvantages. The reductions with hydrazine or NaBH4
and metal do not require the use of hydrogen gas.
F igu r e 1. The apparatus of electrolysis for generation of
active nickel.
However, a significant disadvantage is that the reaction
with hydrazine also reduces carbonyl groups substituted
Electrolysis was carried out in a DMF solution containing
0.3 M Bu4NBF4 using an undivided cell with a platinum
cathode and a nickel anode at constant current under
an argon atmosphere to give a highly reactive nickel-
DMF suspension without massive deposition (Figure 1).
We report here the reduction of nitrobenzenes to
anilines by electrogenerated nickel at room temperature
in a short time without affecting various functional
groups.
on nitrobenezenes while the reduction with the combina-
5-7
tion of NaBH4
and metal often involves dehalogena-
tion. Also, the reduction with RuCl2(PPh3)2-H2 requires
a high temperature and pressure.8 Recently, Fischer and
co-workers reported that diethyl chlorophosphite could
reduce aromatic nitrobenzenes.9 However, the reduction
of nitrobenzenes having a cyano or methoxy group
produced only low yields.
On the other hand, we reported the easy preparation
of a highly reactive nickel by an electrochemical method.10
Resu lts a n d Discu ssion
* Corresponding author. Tel +81-22-217-6867; fax +81-22-217-6864;
yasuhara@mail.pharm.tohoku.ac.jp
As shown in Figure 1, highly reactive nickel was
prepared by electrolysis in a DMF solution containing
0.3 M tetraethylammonium tetrafluoroborate (Et4NBF4)
or tetrabutylammonium tetrafluoroborate (Bu4NBF4)
under an argon atmosphere. In this reaction, Et4NBF4
was used as the electrolyte, because Et4NBF4 could be
more easily removed by extraction than Bu4NBF4. The
electrolysis was carried out at a constant current of 10
mA/cm2 at 0 °C for 1158 Coulombs (ca. 4 h). The
electrolysis of 1158 Coulombs prepared 2.5 mmol nickel
using a platinum cathode (1 × 2 cm) and nickel anode (1
× 2 cm). After the electrolysis, the nickel-DMF suspen-
sion was transferred to a reaction flask using a syringe
and was used for reduction of 0.5 mmol of nitrobenzenes.
As shown in Table 1, the reduction of the nitrobenzenes
(1) (a) Gilman, H. Organic Syntheses; J ohn Wiley & Sons: New
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254. (c) Horning, E. C. Organic Syntheses; J ohn Wiley & Sons: New
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5149-5150. Balcom, D.; Furst, A. J . Am. Chem. Soc. 1953, 75, 4334.
Kozuka, M.; Iwaizumi, M. Bull. Chem. Soc. J pn. 1983, 56, 3165-3166.
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2829.
(7) Satoh, T.; Suzuki, S. Tetrahedron Lett. 1969, 4555-4558.
(8) Knifton, J . F. J . Org. Chem. 1976, 41, 1200-1205.
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10.1021/jo981935p CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/18/1999

2302 J . Org. Chem., Vol. 64, No. 7, 1999
Yasuhara et al.
Ta ble 1. Red u ction of 4-Nitr oben zen es to Am in es w ith
Electr ogen er a ted Nick el
Ta ble 2. Red u ction of 2-Nitr oben zen es in to Am in es w ith
Electr ogen er a ted Nick el
The electrolysis time depended on the electrode area.
Therefore, the electrogenerated nickel was prepared on
a 3 mmol scale and had the same reactivity with the
nickel prepared on the 0.5 mmol scale. In the case of the
3 mmol scale, the electrolysis using a nickel anode (2 ×
6 cm) and platinum cathode (2 × 6 cm) was carried out
for 5790 Coulombs (ca. 4 h). The reduction of 4-bromoni-
trobenzene (606 mg, 3 mmol) with the nickel-DMF
suspension gave 4-bromoaniline (387 mg, 75%).
Con clu sion
gave the corresponding anilines in a short time at room
temperature. The reduction of 4-halonitrobenzene with
the electrogenerated nickel proceeded in 15 min at room
temperature with 76-83% yields. Especially, the elec-
trogenerated nickel could selectively reduce the nitro
group of 4-iodonitrobenzene in which the iodo group has
a high reactivity for the oxidative addition of nickel in
good yield without deiodination (Table 1, entry 1). The
reduction of nitrobenzenes with carbonyl groups such as
the acetyl (1d ), formyl (1i), and ethoxycarbonyl groups
(1g) also gave the corresponding anilines in 62, 56, and
87% yields, respectively. Also the reduction of alkene (1g)
and alkyne (1h ) with electrogenerated nickel proceeded
in 87 and 94% yields without affecting the unsaturated
carbon-carbon bonds. Although the reduction of 4-nitro-
1-(phenylmethoxy)benzene (1j) with 5 equiv of nickel did
not completely proceed and gave 2j in 22% yield (Table
1, entry 10), the reduction with 10 equiv of nickel
proceeded for 18 h at room temperature and produced
2j in 86% yield (Table 1, entry 11). The reduction of
nitrobenzenes with the phenylsufonylamino (1k ) and
allyloxy groups (1l) gave the corresponding anilines in
low yields (47 and 35% yields). In the later case, deallyl-
ation of 1l preceded without reduction of the nitro group
to give 4-nitrophenol in 12% yield.
The reduction of nitrobenzenes to anilines using elec-
trogenerated nickel proceeds under mild conditions with-
out affecting various functional groups on the aromatic
ring. The reaction was usually performed at room tem-
perature for 15 min. No co-reducing agents or hydrogen
gas were required. Moreover, it was found that the
reactive nickel can be stored for a week at -20 °C without
losing its reactivity for the reduction of the nitrobenzenes.
The electrogenerated nickel can be concluded to be a good
reducing reagent for nitrobenzenes.
Exp er im en ta l Section
All melting points and boiling points are uncorrected. The
IR spectra were measured on a J ASCO IR-810 spectropho-
tometer. H NMR spectra were recorded on a Varian Gemini
1
2000 (300 MHz). Chemical shifts are expressed in δ (ppm)
values with tetramethylsilane (TMS) as the internal reference,
and coupling constants are expressed in hertz (Hz). Mass
spectra (MS) and high-resolution mass spectra (HRMS) were
recorded on J MS-DX303 and J MS-AX500 instruments, respec-
tively.
P r ep a r a tion of Electr ogen er a ted Nick el. A platinum
sheet (1 × 2 cm2) as the cathode and a nickel sheet (1 × 2
cm2) as the anode were placed in a 15 mL H-shaped undivided
cell that contained 0.3 M Et4NBF4-DMF (8 mL). Electrolysis
was carried out under an argon atmosphere at a constant
current of 10 mA/cm2 at 0 °C until 1158 coulombs of electricity
had passed to produce a black suspension containing the active
nickel (145 mg, 2.4 mmol).
The amount of Ni in a black suspension was confirmed by
following method. After electrolysis, dry THF (30 mL) was
added to the black nickel suspension, the mixture was
centrifuged (3500 rpm, 1 h), and the supernatant was dis-
carded. Dry THF was added to the precipitate, the mixture
was stirred and centrifuged (3500 rpm, 10 min), and the
supernatant was discarded. The precipitate was dried under
reduced pressure, and the weight of precipitate was measured.
Gen er a l P r oced u r e for Red u ction of Su bstitu ted Ni-
tr oben zen es. The nickel-DMF suspension was added to a
substituted nitrobenzene (0.5 mmol) using a syringe under an
argon atmosphere. The mixture was stirred for 15 min (or 18
h) at room temperature. 2 M HCl (10 mL) was added to the
reaction mixture. After the addition of Et2O (20 mL) to the
solution, the mixture was filtered through a Celite pad. The
The reduction of 2-substituted nitrobenzenes using the
electrogenerated nickel proceeded in lower yields than
the reduction of the 4-substituted nitrobenzenes (Table
2). The reduction of 2-iodo- (3a ), 2-acetyl- (3d ), 2-meth-
oxy- (3e), and 2-(phenylethynyl)nitrobenzene (3h ) pro-
ceeded in 36-70% yields, and the yields of the corre-
sponding 4-substituted nitrobenzenes were 62-93%.
We investigated the storage stability of the electro-
generated nickel and scaling-up the reaction (3 mmol
scale of the starting material). After the electrogenerated
nickel has been stored for 1 week at -20 °C under an
argon atmosphere, the reduction of 4-bromonitrobenzene
with the nickel gave the 4-bromoaniline in 75% yield. The
reaction of the same starting material with the fresh
electrogenerated nickel gave the product in 78% yield
(Table 1, entry 2).

Reduction of Nitrobenzenes to Anilines
J . Org. Chem., Vol. 64, No. 7, 1999 2303
ethereal layer was separated and extracted with 2 M HCl (15
mL × 3). The aqueous layers were combined, made basic with
K2CO3, and extracted with Et2O (20 mL × 3). The ethereal
layer was washed with H2O (10 mL), dried over MgSO4, and
evaporated under reduced pressure. The residue was purified
by recrystallization or distillation.
4-(P h en ylm eth oxy)a n ilin e (2j). White solid; bp 145-155
°C/3 mmHg (lit.3b 201-202 °C/11 mmHg); 1H NMR (CDCl3/
TMS) δ: 3.25 (br, 2H), 4.99 (s, 2H), 6.64 (d, J ) 8.8 Hz, 2H),
6.82 (d, J ) 8.8 Hz, 2H), 7.31-7.44 (m, 5H); MS m/z: 199 (M+);
IR ν (KBr) cm-1: 3430, 3370.
(4-Am in op h en yl)ben zen esu lfon a m id e (2k ). Colorless
4-Iod oa n ilin e (2a ). Colorless needles from Et2O-hexane;
needles from EtOAc-hexane; mp 170-173 °C (lit.14 171-174
1
mp 59-60 °C (lit.11 mp 63-65 °C); H NMR (CDCl3/TMS) δ:
1
°C); H NMR (CDCl3/TMS) δ: 3.62 (br, 3H), 6.54 (d, J ) 8.8
3.15 (br, 2H), 6.47 (d, J ) 8.7 Hz, 2H), 7.41 (d, J ) 8.7 Hz,
Hz, 2H), 6.81 (d, J ) 8.8 Hz, 2H), 7.43 (d, J ) 7.4 Hz, 2H),
7.54 (t, J ) 7.4 Hz, 1H), 7.69 (d, J ) 7.4 Hz, 2H); MS m/z:
248 (M+); IR ν (KBr) cm-1: 3410, 3340, 1320, 1160.
2H); IR ν (KBr) cm-1: 3400, 3290.
4-Br om oa n ilin e (2b). Colorless prisms from Et2O-hexane;
1
mp 59-61 °C (lit.11 mp 62-64 °C); H NMR (CDCl3/TMS) δ:
4-(P r op -2-en yloxy)a n ilin e (2l). According to the general
procedure of the reduction of substituted nitrobenzenes, the
reaction of 1l with the nickel-DMF suspension gave a crude
product. The crude product was purified by column chroma-
tography and distillation. Colorless viscous liquid; bp 55-65
°C/3 mmHg; 1H NMR (CDCl3/TMS) δ: 3.35 (br, 2H), 4.46 (dt,
J ) 5.5, 1.5 Hz, 2H), 5.26 (ddd, J ) 10.4, 2.0, 1.5 Hz, 1H),
5.39 (ddd, J ) 17.0, 2.0, 1.5 Hz, 1H), 6.04 (ddd, J ) 17.0, 10.4,
5.5 Hz, 1H), 6.64 (d, J ) 8.8 Hz, 2H), 6.77 (d, J ) 8.8 Hz, 2H);
MS m/z: 149 (M+); HRMS Calcd for C9H11NO 149.0840. Found
149.0841; IR ν (KBr) cm-1: 3410, 3350, 1630, 1240. Anal. Calcd
for C9H11NO: C, 72.46; H, 7.43; N, 9.39. Found: C, 72.40; H,
7.45; N, 9.34.
3.65 (br, 2H), 6.57 (d, J ) 8.8 Hz, 2H), 7.24 (d, J ) 8.8 Hz,
2H); IR ν (KBr) cm-1: 3470, 3380.
4-Ch lor oa n ilin e (2c). Colorless prisms from Et2O-hexane;
mp 67-69 (lit.11 mp 68-71 °C); 1H NMR (CDCl3/TMS) δ: 3.65
(br, 2H), 6.61 (d, J ) 8.8 Hz, 2H), 7.10 (d, J ) 8.8 Hz, 2H); IR
ν (KBr) cm-1: 3470, 3380.
4-Am in op h en yl Meth yl Keton e (2d ). Colorless prisms
from EtOAc-hexane; mp 104-106 °C (lit.11 mp 105-107); 1H
NMR (CDCl3/TMS) δ: 2.51 (s, 3H), 4.12 (br, 2H), 6.65 (d, J )
8.5 Hz, 2H), 7.82 (d, J ) 8.5 Hz, 2H); MS m/z: 135 (M+); IR ν
(KBr) cm-1: 3370, 3300, 1640.
4-Meth oxya n ilin e (2e). Colorless prisms from Et2O-
hexane; mp 53-55 °C (lit.12 57-60 °C); 1H NMR (CDCl3/TMS)
δ: 3.42 (br, 2H), 3.75 (s, 3H), 6.65 (d, J ) 8.8 Hz, 2H), 6.71 (d,
J ) 8.8 Hz, 2H); IR ν (KBr) cm-1: 3420, 3345, 1230.
4-Am in oben zon itr ile (2f). Colorless prisms from Et2O-
hexane; mp 83-85 °C (lit.11 83-85 °C); 1H NMR (CDCl3/TMS)
δ: 4.15 (br, 2H), 6.65 (d, J ) 8.8 Hz, 2H), 7.42 (d, J ) 8.8 Hz,
2H); IR ν (KBr) cm-1: 3470, 3360, 2210.
2-Iod oa n ilin e (4a ). Colorless needles from Et2O-hexane;
mp 52-55 °C (lit.11 mp 58 °C); 1H NMR (CDCl3/TMS) δ: 4.09
(br, 2H), 6.48 (t, J ) 7.9 Hz, 1H), 6.76 (d, J ) 7.9 Hz, 1H),
7.14 (t, J ) 7.9 Hz, 1H), 7.64 (t, J ) 7.9 Hz, 1H); IR ν (KBr)
cm-1: 3390, 3290.
2-Am in op h en yl Meth yl Keton e (4d ). Pale yellow, viscous
liquid; bp 95-105 °C/3 mmHg (lit.11 85-90 °C/0.5 mmHg); 1H
NMR (CDCl3/TMS) δ: 2.56 (s, 3H), 6.29 (br, 2H), 6.61-6.66
(m, 2H), 7.25 (dt, J ) 8.4, 1.6 Hz, 1H), 7.70 (dd, J ) 8.4, 1.6
Hz, 1H); IR ν (KBr) cm-1: 3450, 3340, 1650.
2-Meth oxya n in lin e (4e). Colorless liquid; bp 120-130 °C/
30 mmHg (lit.11 bp 225 °C/760 mmHg); 1H NMR (CDCl3/TMS)
δ: 3.77 (br, 2H), 3.83 (s, 3H), 6.69-6.80 (m, 5H); IR ν (KBr)
cm-1: 3460, 3370, 1230.
E t h yl 3-(4-Am in op h en yl)p r op en oa t e (2g). Colorless
1
needles from Et2O-hexane; mp 67-68 °C; H NMR (CDCl3/
TMS) δ: 1.32 (t, J ) 7.1 Hz, 3H), 3.95 (br, 2H), 4.24 (q, J )
7.1 Hz, 2H), 6.24 (d, J ) 16.0 Hz, 1H), 6.65 (d, J ) 8.8 Hz,
2H), 7.35 (d, J ) 8.8 Hz, 2H), 7.60 (d, J ) 16.0 Hz, 1H); MS
m/z: 191 (M+); IR ν (KBr) cm-1: 3410, 3320, 1690, 1590. Anal.
Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32. Found: C,
69.16; H, 6.77; N, 7.34.
4-(P h en yleth yn yl)a n ilin e (2h ). Colorless needles from
Et2O-hexane; mp 126-128 °C (lit.13 mp 128-129 °C); 1H NMR
(CDCl3/TMS) δ: 3.81 (br, 2H), 6.64 (d, J ) 8.8 Hz, 2H), 7.36-
7.40 (m, 5H), 7.50 (d, J ) 8.8 Hz, 2H); MS m/z: 193 (M+); IR
ν (KBr) cm-1: 3470, 3380, 2210.
2-(P h en yleth yn yl)a n ilin e (4h ). Pale yellow prisms from
1
hexane-acetone; mp 89-90 °C (lit.9 92 °C); H NMR (CDCl3)
δ 4.27 (br, 2H), 6.79 (t, J ) 7.7 Hz, 2H), 7.14 (dt, J ) 7.9, 1.4
Hz, 1H), 7.32-7.39 (m, 4H), 7.51-7.55 (m, 2H); MS m/z: 193
(M+); IR (KBr) cm-1 3500, 2250, 1620.
4-Am in ob en za ld eh yd e (2i). Pale yellow solid; unstable
1
compound; H NMR (CDCl3/TMS) δ: 4.37 (br, 2H), 6.70 (d, J
) 8.5 Hz, 2H), 7.68 (d, J ) 8.5 Hz, 2H), 9.74 (s, 1H); MS m/z:
121 (M+); HRMS Calcd for C7H7NO: 121.0527. Found:
121.0525. IR ν (KBr) cm-1: 3360, 1665.
Ack n ow led gm en t. This research was supported by
a Grant-in-Aid for Scientific Research (No 10771234)
from the Ministry of Education, Science, Sports and
Culture of J apan.
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FT-NMR Spectra 2; Aldrich Chemical Co., Inc.: New York, 1993; pp
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