Chemoselective reduction of aromatic nitro and azo compounds in ionic liquids using zinc and ammonium salts

Article abstract of DOI:10.1016/j.tetlet.2003.08.080

Nitroarenes were chemoselectively reduced to the corresponding amines using zinc and aqueous ammonium salts in ionic liquids as a safe and recyclable reaction medium. Our results specify the effect of ammonium salts in the process; the combination of Zn/NH₄Cl in [bmim][PF₆] or Zn/HCO₂NH₄ in [bmim][BF₄] were the suitable conditions for the reduction of nitroarenes. Azobenzenes were also smoothly reduced to hydrazobenzenes with Zn/HCO₂NH₄ (aq.) in recyclable [bmim][BF₄] without any over reduction to the corresponding anilines.

Full text of DOI:10.1016/j.tetlet.2003.08.080

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7783–7787
Chemoselective reduction of aromatic nitro and azo compounds
in ionic liquids using zinc and ammonium salts
Faiz Ahmed Khan,* Jyotirmayee Dash, Ch. Sudheer and Rakesh Kumar Gupta
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Received 23 July 2003; revised 8 August 2003; accepted 20 August 2003
Abstract—Nitroarenes were chemoselectively reduced to the corresponding amines using zinc and aqueous ammonium salts in
ionic liquids as a safe and recyclable reaction medium. Our results specify the effect of ammonium salts in the process; the
combination of Zn/NH Cl in [bmim][PF ] or Zn/HCO NH in [bmim][BF ] were the suitable conditions for the reduction of
4
6
2
4
4
nitroarenes. Azobenzenes were also smoothly reduced to hydrazobenzenes with Zn/HCO NH (aq.) in recyclable [bmim][BF ]
2
4
4
without any over reduction to the corresponding anilines.
2003 Elsevier Ltd. All rights reserved.
©
The development of practical methodologies using con-
venient reaction media which are more environmentally
benign, is one of the leading concerns of any chemical
synthesis. In recent years, the use of ionic liquids as a
recyclable reaction medium, to replace volatile organic
nitroarenes using zinc metal require an organic solvent,
corrosive reagents such as NH , conc. HCl, aq. NaOH,
3
high temperatures, prolonged reaction times and more-
over use substantial amounts of zinc metal. Although
reduction in an aqueous medium employing 7.25 equiv.
1
10
solvents has received considerable attention. Some of
of Zn at 80°C was reported recently, the advantage
the important reactions which have been successfully
executed in ionic liquids are transition metal-catalyzed
with ionic liquids is the high solubility of nitro sub-
strates at ambient temperature, making it more general.
2
3
4
olefin hydrogenation, oxidation, Diels–Alder6 and
5
Wittig reactions, metal-mediated allylations, etc.
We probed the title reaction employing [bmim][PF ]
6
11
However, to date metal-mediated reductions in ionic
and [bmim][BF ] as ionic liquids and evaluated the
4
7
liquids have received little attention. We report herein
suitability of various ammonium salts as additives. Our
a convenient and practically simple procedure for zinc-
mediated chemoselective reduction of aromatic nitro
compounds to amines using ammonium salts in imida-
zolium ionic liquids in 73–94% of yield. This, to our
knowledge, is the first report of zinc-mediated reduc-
tions in ionic liquids.
investigations revealed that for [bmim][PF ], ammo-
nium chloride is the additive of choice while
6
[bmim][BF ] gave good results in the presence of
4
ammonium formate (Table 1). Use of 4 equiv. of Zn, 3
equiv. of ammonium salt in 10:1 ionic liquid and water
gave a clean reaction to furnish aniline from nitroben-
zene. Formation of side-products such as azoxy- and
azo- (or hydrazobenzene, in some cases) resulted in
changing ammonium salt, but were significantly sup-
pressed in favor of aniline by increasing the amount of
zinc to six equivalents (entries 3, 5, 7 and 8). Interest-
ingly, the reaction did not proceed in the absence of
either ammonium salt or water.
The reduction of nitroarenes to the corresponding
amines is an important transformation since many aro-
matic amines exhibit biological activities and find a
multitude of industrial applications, being intermediates
for the synthesis of dyes, pharmaceuticals, and agricul-
tural chemicals. There are a variety of methods for the
reduction of nitro compounds reported in the literature;
8
the most popular being catalytic hydrogenation and
Mechanistically, reduction of a nitro group to amino is
9
metal-mediated reduction. Conventional reductions of
9b,c
known
to involve nitroso 6 and hydroxylamine 4
intermediates, which are considered to be responsible
for the formation of azoxy- 2, azo- 3 and hydrazoben-
zene 7 as depicted in Scheme 1. However, cleavage of
the NꢀN bond of hydrazobenzene 7 to aniline 5,
Keywords: ionic liquids; zinc; reduction; nitroarenes; anilines; azo
compounds; hydrazobenzenes.
*
Corresponding author. Tel.: +91-512-2597864; e-mail: faiz@
9c,12
iitk.ac.in
reported to be a facile reaction,
is ruled out under
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.080

7
784
F. A. Khan et al. / Tetrahedron Letters 44 (2003) 7783–7787
a
Table 1. Zinc mediated reduction of nitrobenzenes in ionic liquids using different ammonium salts
Ratiob
Yield (%)
c
Entry
Ammonium salts
Ionic liquid
Time (h)
1
2
3
4
5
6
7
8
NH Cl
[bmim][PF6]
[bmim][PF6]
[bmim]PF6]
[bmim][PF6]
[bmim][PF6]
[bmim][BF4]
[bmim][BF4]
[bmim][BF4]
7
5
93
89
80
94
83
89
81
80
4
NH Cl
2.5
2.5
7.5
10
10
16
1:4:5 35:39:26
2:3:5 (9:3:88)
5
2:3:5 (5:2:93)
5
2:3:5 7:6:87
2:3:5 (23:5:72)
4
d
HCO NH
2
4
NH Cl
4
d
HCO NH
2
4
HCO NH
2
4
d
NH Cl
4
d
(NH ) SO
19
4
2
4
Entries 1–3, 6 (Ar=Ph), 4, 5, 7–8 (Ar=p-MePh).
a
Zn (4 equiv.), 3 equiv. of NH Cl or HCO NH or 1.5 equiv. of (NH ) SO by vigorously stirring in ionic liquids.
The product distributions in all cases were determined by H NMR integration at 400 MHz of the unpurified product mixtures obtained after
4
2
4
4 2
4
b
1
ether extraction.
Total yields of analytically pure products.
c
d
6
equiv. of Zn.
excellent purity for most purposes. The ionic liquids
1
5
were easily recycled. Thus, both [bmim][PF ] and
6
[
bmim][BF ] were reused to give the products without
4
any decrease in yield or purity of the products (Table
).
3
The ionic liquid [bmim][PF ] was successfully reused for
6
the successive reduction of three different nitrobenzenes
to provide the corresponding amines in high yield
Scheme 1.
(
Table 4). No cross contamination of products was
1
observed by 400 MHz H NMR analysis.
our reaction conditions as substantiated by selective
reduction of azo- to hydrazobenzenes (vide infra). In
accordance with the mechanistic proposal, we detected
either hydroxylamine 4 or azoxy- 2, azo- 3 and hydra-
zobenzene 7 by intercepting the reaction by giving
insufficient time (entry 2) or by using incompatible
additives (entries 3, 5, 7 and 8).
After achieving Zn-mediated efficient reduction of aro-
matic nitro compounds in ionic liquids, we employed
the reaction system for the reduction of azobenzenes.
The reduction of azobenzenes to hydrazobenzenes has
been carried out using catalytic hydrogenation and a
16
variety of other reduction methods. However, most
chemical methods require harsh reaction conditions,
associated with poor yields, and lack of selectivity, since
hydrazo derivatives undergo easy reductive cleavage to
furnish amines. Furthermore, conventional Zn-medi-
On the basis of the optimized conditions (Table 1), the
reduction of nitroarenes were performed with Zn (4
equiv.)/NH Cl (3 equiv.) in 10:1 [bmim][PF ]/water
17
4
1
6
ated reduction requires carefully controlled conditions
to avoid benzidine rearrangement.
3
(
1
Method A) and Zn (4 equiv.)/HCO NH (3 equiv.) in
0:1 [bmim][BF ]/water (Method B) under an inert
2
4
1
4
4
atmosphere (Table 2). A number of aromatic nitro
compounds were smoothly reduced to give excellent
yields of the corresponding amines in either ionic sol-
vent (Table 2). It was essential that the ionic liquid was
thoroughly de-oxygenated under vacuum, to remove
dissolved oxygen, before use and the reactions were
The azobenzene was treated with 4 equiv. of Zn,
HCO NH (3 equiv.) in 10:1 [bmim][BF ] and water
2
4
4
18
(
entry 1, Table 5). The reaction was completed within
2
5 minutes to furnish near quantitative yields of hydra-
zobenzenes. The reduction of azobenzene was found to
be relatively slow in [bmim][PF ], nevertheless hydra-
6
found to be more sensitive in [bmim][BF ] than
4
zobenzene was obtained in 96% yield (Table 5, entry 2).
The reaction was generalized for other azobenzenes to
give hydrazobenzenes in high yield (Table 5). The ionic
[
bmim][PF ]. The reaction time as well as the yield of
6
the reaction was perceptibly better in [bmim][PF ]. In
6
the course of the process, substituents such as chloro,
iodo, fluoro, hydroxy or ketone were not affected.
liquid [bmim][BF ] could be recycled effectively (Table
4
6
).
The separation of products from ionic liquids is simple
and involves, in most of the cases, direct extraction
with ether. The crude product, so isolated, was of
In summary, we have demonstrated the zinc-mediated
smooth reduction of nitroarenes to amines and azoben-
zenes to hydrazobenzenes in ionic liquids in the pres-

F. A. Khan et al. / Tetrahedron Letters 44 (2003) 7783–7787
7785
Table 2. Zinc-mediated reduction of aromatic nitro compounds to amines in ionic liquids
ence of suitable ammonium salts. The advantages
include a safe reaction medium, high selectivity, easy
product isolation and simple recovery of ionic liquids.
Table 3. Recycling of ionic liquids for the reduction of
nitrobenzene to aniline
Cycle
1
2
3
4
Acknowledgements
Yield (%), using [bmim][PF ] (Method A)
93
87
95
93
92
86
87
6
Yield (%), using [bmim][BF ] (Method B)
We thank the Department of Science and Technology
4
(
DST), the Council of Scientific and Industrial

7
786
F. A. Khan et al. / Tetrahedron Letters 44 (2003) 7783–7787
Table 4. Recycling ionic liquids: crossed experiments
Chem., Int. Ed. 2000, 39, 3772–3789; (c) Sheldon, R. A.
Chem. Commun. 2001, 2399–2407; (d) Dupont, J.; de-
Souza, R. F.; Suarez, P. A. Z. Chem. Rev. 2002, 102,
3667–3692.
2
3
. (a) Steines, S.; Drieben-Holscher, B.; Wasserscheid, P. J.
Prakt. Chem. 2000, 342, 348–354; (b) Dyson, P. J.; Ellis,
D. J.; Parker, D. G.; Welton, T. Chem. Commun. 1999,
Substrate (Ar)
Ph
Cycle
Time (h)
Yield (%)a
25–26.
. (a) Ansari, I. A.; Gr e´ e, R. Org. Lett. 2002, 4, 1507–1509;
1
2
3
7
8
7
91
95
89
(
(
b) Farmer, V.; Welton, T. Green Chem. 2002, 4, 97–102;
c) Ley, S. V.; Ramarao, C.; Smith, M. D. Chem. Com-
(
(
p-MeC H )
6 4
p-ClC H )
6
4
mun. 2001, 2278–2279.
a
4. (a) Earle, M. J.; McCormac, P. B.; Seddon, K. R. Green
Chem. 1999, 23–25; (b) Fischer, T.; Sethi, A.; Welton, T.;
Woolf, J. Tetahedron Lett. 1999, 40, 793–796.
Isolated yields of pure amines. No contamination of products was
observed for the experiments conducted.
a
Table 5. Reduction of azobenzene to hydrazobenzene
5. Boulaire, V. L.; Gr e´ e, R. Chem. Commun. 2000, 2195–
2
196.
. (a) Gordon, C. M.; Ritchie, C. Green Chem. 2002, 4,
24–128; (b) Law, M. C.; Wong, K. Y.; Chan, T. H.
6
1
Green Chem. 2002, 4, 161–164.
7
. For a singe report on Sm promoted reduction of aro-
matic nitro compounds in ionic liquid, see: Zheng, X. L.;
Zhang, Y. M. Chinese J. Chem. 2002, 20, 925–928.
. Tafesh, A. M.; Weiguny, J. Chem. Rev. 1996, 96, 2035–
8
9
2
052.
. (a) Martin, E. L. Org. Synth. 1943, Coll. Vol. II, 501–503;
b) Yu, C.; Liu, B.; Hu, L. J. Org. Chem. 2001, 66,
19–924; (c) Brady, E. D.; Clark, D. L.; Keogh, D. W.;
Scott, B. L.; Watkin, J. G. J. Am. Chem. Soc. 2002, 124,
(
9
7007–7015; (d) Moody, C. J.; Pitts, M. R. Synlett 1998,
1028.
1
1
0. Tsukinoki, T.; Tsuzuki, H. Green Chem. 2001, 3, 37–38.
1. 1-Butyl-3-methylimidazolium hexafluorophosphate,
bmim][PF6], and 1-butyl-3-methylimidazolium tetra-
[
fluoroborate, [bmim][BF ], were prepared following: (a)
4
Guernik, S.; Wolfson, A.; Herskowitz, M.; Greenspoon,
N.; Geresh, S. Chem. Commun. 2001, 2314–2315, (b)
Suarez, P. A. Z.; Dullius, J. E. L.; Einloft, S.; de-Souza,
R. F., Dupont, J. Polyhedron 1996, 15, 1217–1219.
12. Gowda, S.; Abiraj, K.; Gowda, D. C. Tetrahedron Lett.
2
002, 43, 1329–1331.
3. General procedure for reduction of nitroarenes in
bmim][PF ] (Method A): Nitroarene (0.5 mmol), zinc
1
[
6
metal (2 mmol), NH Cl (1.5 mmol) and water (0.1 ml)
4
were added to [bmim]PF (1 ml) and vigorously stirred at
6
room temperature for the specified time under an argon
atmosphere (Table 2). After consumption of the starting
Table 6. Recycling of [bmim][BF ] for the reduction of
4
azobenzene
material, as monitored by TLC, Et O (3×5 ml) was added
2
to the reaction mixture (a white suspension) with vigor-
ous stirring for 5 min. The mixture was allowed to stand
for 4 min and the clear supernatant liquid was decanted
Cycle
1
2
3
4
Yield (%)
98
94
100
96
(
through a filter paper). The combined ether extracts were
concentrated to dryness and the crude product was found
1
13
to be sufficiently pure (400 MHz H NMR, 100 MHz
C
Research (CSIR), New Delhi for financial assistance.
J.D., R.K.G. and C.S. thank CSIR, U.G.C. for
fellowships.
NMR) in most of the cases. Where necessary, the crude
product was purified by SiO column chromatography. In
2
cases (Table 2, entries 11–14), where the products were
not fully extracted with diethyl ether, the reaction mix-
ture was dissolved in CH Cl (EtOAc can also be used in
2
2
References
place of CH Cl ), filtered, concentrated and then passed
2 2
through a small silica gel column to afford the pure
1
. For recent reviews, see: (a) Welton, T. Chem. Rev. 1999,
amines first, in the specified yields (Table 2), followed by
the recovery of the ionic liquid (400 MHz H NMR).
1
9
9, 2071–2083; (b) Wasserscheid, P.; Keim, W. Angew.

F. A. Khan et al. / Tetrahedron Letters 44 (2003) 7783–7787
7787
14. General procedure for reduction of nitroarenes in
The results are listed under Table 3. Similarly, the ionic
[
bmim][BF ] (Method B): To a solution of nitroarene (0.5
liquid [bmim][BF ] was recycled and used for three runs
4
4
mmol) in [bmim]BF4 (1 ml), zinc metal (2 mmol),
(Table 3).
HCO NH (1.5 mmol) and water (0.1 ml) were added and
16. (a) Alberti, A.; Bedogni, N.; Benaglia, M.; Leardini, R.;
Nanni, D.; Pedulli, G. F.; Tundo, A.; Zanardi, G. J. Org.
Chem. 1992, 57, 607–613; (b) Park, K. K.; Han, S. Y.
Tetrahedron Lett. 1996, 37, 6721–6724; (c) Patil, M. L.;
Jnaneshwara, G. K.; Sabde, D. P.; Dongare, M. K.;
Sudalai, A.; Deshpande, V. H. Tetrahedron Lett. 1997,
2
4
vigorously stirred at room temperature for the specified
time under an argon atmosphere (Table 2). After con-
sumption of the starting material, as monitored by TLC,
Et O (3×5 ml) was added to the reaction mixture (a white
2
suspension) with vigorous stirring for 5 min. The mixture
was allowed to stand for 4 min and the clear supernatant
liquid was decanted (through a filter paper). The com-
bined ether extracts were concentrated to dryness and the
crude product was found to be analytically pure (400
3
8, 2137–2140 and references cited therein.
7. (a) Carlin, R. B.; Forshey, W. O., Jr. J. Am. Chem. Soc.
950, 72, 793–801; (b) Shine, H. J.; Trisler, J. C. J. Am.
1
1
Chem. Soc. 1960, 82, 4054–4058.
1
13
MHz H NMR, 100 MHz C NMR) in most of the
1
8. Reduction of azobenzene: Azobenzene (0.5 mmol), zinc
metal (2 mmol, 131 mg), HCO NH (93 mg, 3 mmol) and
cases. Where necessary, the crude product was purified by
2
4
SiO column chromatography.
2
water (0.1 ml) were added to [bmim][BF ] (1 ml) and the
4
1
5. Recycling experiments in [bmim][PF ]: The ionic liquids
6
mixture was vigorously stirred at rt for the specified time
were recovered as follows after each cycle: The residue
containing ionic liquid was dissolved in minimum amount
(
consumption of the starting material, as monitored by
TLC, Table 5). Ether (3×5 ml) was added to the reaction
mixture, stirred for a few minutes and decanted. The
combined ether extracts were concentrated to dryness to
give hydrazobenzenes in the specified yields (Table 5).
of CH Cl2 (or EtOAc), filtered through a filter paper,
2
dried over Na SO4 and the solvent was removed on a
2
rotary evaporator. The ionic liquid was further dried at
7
0°C and 0.1 mmHg for 4 h. The recovered ionic liquid
1
The residue was dissolved in CH Cl (or EtOAc), filtered,
was analyzed by H NMR and there was none of the
amine product in it. This reaction was repeated for three
more cycles using the ionic liquid recovered from the
previous run under identical conditions as for cycle 1.
2 2
concentrated and dried under vacuum at 70°C and 0.1
mmHg for 1 h and reused for three more runs under
identical conditions (Table 6).