1028
LETTERS
SYNLETT
Indium as a Reducing Agent: Reduction of Aromatic Nitro Groups
Christopher J. Moody and Michael R. Pitts
Department of Chemistry, University of Exeter, Stocker Road, Exeter, EX4 4QD, U.K.
Fax: + 1392 263434, E-mail: c.j.moody@exeter.ac.uk
Received 5 June 1998
Abstract: Treatment of a range of aromatic nitro compounds with
indium powder in aqueous ethanolic ammonium chloride results in
selective reduction of the nitro groups; ester, nitrile, amide and halide
substituents are unaffected.
Although a large number of methods for the reduction of aromatic nitro
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compounds has been developed, many of these are incompatible with
other functional groups in the molecule. For example, the selective
reduction of nitro groups in the presence of carbonyl groups, nitriles,
halides, and alkenes is often difficult, and in such cases catalytic
hydrogenation, which is often the method of choice for nitro reduction,
is inappropriate. Thus, hydrogenation of 4-chloro-3-nitroacetophenone
over Pd/C results in hydrogenolysis of the halide, and reduction of the
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ketone as well as the nitro group. Consequently new methods for the
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selective reduction of nitro groups continue to be developed. We now
report a mild new method for the reduction of aromatic and hetero-
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aromatic nitro groups using indium metal (Scheme 1).
Scheme 1
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As part of a wider study on the use of indium metal as a reducing agent,
we found that the reduction of aromatic nitro compounds proceeded
readily on heating the substrate with indium powder in aqueous
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ethanolic ammonium chloride. The reactions are extremely easy to
carry out, are typically complete within 1 - 3 hours, and give the
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corresponding aniline in good to excellent yield (Table). The reaction
conditions are compatible with halogen substituents (Cl, Br, I), carbonyl
groups (acid, ester, amide) and nitriles, and the reduction is not affected
by the presence of sulfur containing substituents. In 6-nitroquinoline
and 5-nitroisoquinoline, the nitro group is reduced before the
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heterocyclic ring.
In conclusion, the use of indium metal for the selective reduction of
aromatic nitro compounds is simple, occurs under mild conditions
results in high yields, compares favourably with known methods, and
therefore should prove a valuable addition to synthetic methodology.
(4) There is a reported example of an apparent nitro group reduction in
the presence of indium metal during an attempted addition of the
allylindium reagent to 4-nitrobenzaldehyde (Chan, T. H.; Isaac, M.
B. Pure Appl. Chem. 1996, 68, 919-924).
References and Notes
(1) For reviews, see: Larock, R. C. Comprehensive Organic
Transformations, VCH: New York, 1989, pp. 411-415; Kabalka, G.
W.; Varma, R. S. Comprehensive Organic Synthesis; Trost, B. M.;
Fleming, I. Eds.; Pergamon Press: Oxford, 1991; Vol. 8; pp. 363-
379; Sauvé, G.; Rao, V. S. Comprehensive Organic Functional
Group Transformations; Katritzky, A. R.; Meth-Cohn, O.; Rees, C.
W. Eds.; Pergamon Press: Oxford, 1995; Vol. 2; pp. 737-817.
(2) Tafesh, A. M.; Weiguny, J. Chem. Rev. 1996, 96, 2035-2052.
(3) For recent examples, see: Boothroyd, S. R.; Kerr, M. A. Tetrahedron
Lett. 1995, 36, 2411-2414; Suwinski, J.; Wagner, P.; Holt, E. M.
Tetrahedron 1996, 52, 9541-9552; Upadhya, T. T.; Katdare, S. P.;
Sabde, D. P.; Ramaswamy, V.; Sudalai, A. Chem. Commun. 1997,
1119-1120; Fischer, B.; Sheihet, L. J. Org. Chem. 1998, 63, 393-
395; Kumbhar, P. S.; Sanchez-Valente, J.; Figueras, F. Tetrahedron
Lett. 1998, 39, 2573-2574.
(5) Moody, C. J.; Pitts, M. R. Synlett 1998, 1029.
(6) To a solution of the nitro compound (2.5 mmol) in ethanol (10 ml)
was added saturated ammonium chloride solution (3 ml) and indium
powder (2.0 g). The mixture was stirred under reflux. When the
reaction appeared complete as judged by TLC (typically 1 - 3 hours),
the cooled reaction mixture was diluted with water (50 ml) and
filtered through Celite. The aqueous filtrate was adjusted to pH ~ 9
with NaOH (4 M) and extracted with dichloromethane, ethyl acetate
or ether (3 x 15 ml). The combined organic layers were dried
(MgSO ) and concentrated in vacuo. The crude product was purified
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by flash chromatography to yield the desired product.
(7) The product anilines are known compounds whose data agreed
closely with literature values.