Highly chemoselective reduction of aromatic nitro compounds by copper nanoparticles/ammonium formate

Article abstract of DOI:10.1021/jo800863m

(Chemical Equation Presented) A highly chemoselective reduction of aromatic nitro compounds to the corresponding amino derivatives has been achieved by a combination of copper nanoparticles and ammonium formate in ethylene glycol at 120°C. The reductions are successfully carried out in presence of a wide variety of other reducible functional groups in the molecule, such as Cl, I, OCH₂Ph, NHCH₂Ph, COR, COOR, CN, etc. The reactions are very clean and high yielding.

Full text of DOI:10.1021/jo800863m

SCHEME 1. Coupling of p-Nitroiodobenzene with Thiol
Catalyzed by Cu Nanoparticles
Highly Chemoselective Reduction of Aromatic
Nitro Compounds by Copper Nanoparticles/
Ammonium Formate
Amit Saha and Brindaban Ranu*
Department of Organic Chemistry, Indian Association for the
CultiVation of Science, JadaVpur, Kolkata 700 032, India
ocbcr@iacs.res.in
ReceiVed April 21, 2008
SCHEME 2. Reduction of Aromatic Nitro Compound to
Aniline
chemoselective reduction of aromatic nitro compounds by
copper nanoparticles in combination with ammonium formate
in ethylene glycol (Scheme 2).
A highly chemoselective reduction of aromatic nitro com-
pounds to the corresponding amino derivatives has been
achieved by a combination of copper nanoparticles and
ammonium formate in ethylene glycol at 120 °C. The
reductions are successfully carried out in presence of a wide
variety of other reducible functional groups in the molecule,
such as Cl, I, OCH2Ph, NHCH2Ph, COR, COOR, CN, etc.
The reactions are very clean and high yielding.
Aromatic amines are useful intermediates in the preparation
of dyes, pharmaceuticals, and agricultural chemicals and can
be easily obtained by the reduction of aromatic nitro compounds.
A variety of procedures involving metals and other reducing
agents are available for this purpose.4 However, the selective
reduction of a nitro group in the presence of other reducible
functionalities in a molecule is a challenging task. In addition,
reduction of aromatic nitro compounds often stops at an
intermediate stage, producing hydroxylamines, hydrazines, and
azoarenes as side products.4b Recently a few procedures
involving coinage metal nanoparticles (Au, Ag, Cu/aqueous
NaBH4),5a gold nanoparticles supported on TiO2 or Fe2O3/H2,5b
polymer-supported nanostructured platinum carbonyl cluster,5c
and carbon nanofiber-supported platinum and palladium
nanoparticles5d have been demonstrated for the reduction of nitro
group. However, an alternative efficient, simple, chemoselective,
and cost-effective procedure is highly appreciated.
The experimental procedure for our Cu nanoparticles-medi-
ated reduction is very simple. A mixture of an aromatic nitro
compound, Cu nanoparticles (size 4-6 nm as shown in Figure
1), and ammonium formate was heated at 120 °C in ethylene
glycol. The product was obtained following a standard workup.
A few other protic solvents such as methanol, ethanol, and water
were also investigated; however, none of them gave satisfactory
results.
The use of metal nanoparticles for organic reactions has
attracted tremendous interest in recent times.1,2 As a part of
our activities in this area we have demonstrated very efficient
uses of palladium nanoparticles for the coupling of Vic-
diiodoalkenes with conjugated alkenes,3a Tsuji-Trost reaction,3b
Hiyama coupling,3c and use of copper nanoparticles for aryl-
sulfur bond formation.3d While carrying out the aryl-sulfur bond
formation catalyzed by Cu nanoparticles (20 mol%), we
observed an interesting reduction of the nitro group to an amino
group in trace amount (5%) in the coupling of 4-nitroiodoben-
zene with 4-methylthiophenol (Scheme 1).3d We proposed that
copper hydride (CuH), generated in situ during the reaction, as
delineated in Scheme 1, was responsible for the reduction of
NO2 group. We then investigated the optimization of the reaction
conditions using a stoichiometric amount of Cu nanoparticles
and a convenient hydrogen source toward complete reduction
of the NO2 group. Ammonium formate was found to provide
the best results in terms of yields and reaction time compared
to other hydrogen sources such as hydrazine hydrate and H2
gas. This led us to report here a novel protocol for the
(4) (a) Tafesh, A. M.; Weiguny, J. Chem. ReV. 1996, 96, 2035–2052. (b)
Yu, C.; Liu, B.; Hu, L. J. Org. Chem. 2001, 66, 919–924, and references therein.
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4, 4297–4300. (d) Rahaim Jr, R. J; Maleczka, R. E, Jr Org. Lett. 2005, 7, 5087–
5090. (e) Liu, Y.; Lu, Y.; Prashad, M.; Repic, O.; Blacklock, T. J. AdV. Synth.
Catal. 2005, 347, 217–219. (f) Chandrasekhar, S.; Prakash, S. J.; Rao, C. L. J.
Org. Chem. 2006, 71, 2196–2199. (g) Shi, Q.; Lu, R.; Lu, L.; Fu, X.; Zhao, D.
AdV. Synth. Catal. 2007, 349, 1877–1881. (h) Mandal, P. K.; McMurray, J. S.
J. Org. Chem. 2007, 72, 6599–6601. (i) Chen, B.; Dingerdissen, U.; Krauter,
J. G. E.; Rotgerink, H. G. J. L.; Mobus, K.; Ostgard, D. J.; Panster, P.; Riermeier,
T. H.; Seebald, S.; Tacke, T.; Trauthwein, H. Appl. Catal., A 2005, 280, 17–46.
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Corma, A.; Serna, P. Science 2006, 313, 332–334. (c) Maity, P.; Basu, S.;
Bhaduri, S.; Lahiri, G. K. AdV. Synth. Catal. 2007, 349, 1955–1962. (d) Takasaki,
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D. Angew. Chem., Int. Ed. 2005, 44, 7399–7404. (b) Astruc, D.; Lu, F.; Aranzaes,
J. R. Angew. Chem., Int. Ed. 2005, 44, 7852–7872.
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10.1021/jo800863m CCC: $40.75
Published on Web 07/26/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 6867–6870 6867

TABLE 1. Reduction of Aromatic Nitro Compounds by Cu
a
Nanoparticles/HCOONH4
FIGURE 1. TEM image of Cu nanoparticles.
Several substituted aromatic nitro compounds were subjected
to this procedure to produce the corresponding aromatic amines.
The results are presented in Table 1. 4-Chloro- and 4-iodo-
nitrobenzene (entries 5 and 6, Table 1) were cleanly reduced to
the corresponding anilines without any dehalogenation, which
was often encountered with several procedures such as
hydrogenation.4a,i 6-Nitroquinoline (entry 7, Table 1) was
reduced to 6-aminoquinoline keeping the heterocyclic ring intact.
The O-benzyl, N-benzyl, ketocarbonyl, carboxylic ester, and
nitrile functionalities present in the aromatic ring also remained
unaffected during reduction of the corresponding nitrobenzenes
by this procedure (entries 8-12, Table 1). m-Dinitrobenzene
(entry 13, Table 1) was reduced selectively to m-nitroaniline.
Many conventional procedures involving hydride reducing
agents, hydrogenation, or indium failed to give such high
chemoselectivity.4 However, considerable reduction of the
double bond conjugated to an aromatic ring was observed while
reducing the nitro group (entry 14, Table 1). Similar reduction
of the double bond in 4-allyloxy nitrobenzene was also found
(entry 15, Table 1), although a completely isolated double bond,
such as in 10-undecenoic ethyl ester, remained inert under the
reaction conditions. In addition, the reactions with a vinylic nitro
compound (ꢀ-nitrostyrene), 4-nitrobenzaldehyde, and 4-(N-
benzylimino)-nitrobenzene were messy, giving a mixture of
several unidentified compounds.
The reaction was not initiated at all using ammonium formate
in the absence of Cu nanoparticles. The reaction was also not
very effective with Cu nanoparticles without ammonium for-
mate. Thus, a combination of Cu nanoparticles and ammonium
formate is essential to carry out the reduction. Use of 5 equiv
of ammonium formate led to complete conversion, and a lesser
amount left the reaction incomplete. This might be due to fact
that a portion of the ammonium formate, deposited by sublima-
tion on the wall of the condenser with the progress of the
reaction, remained unavailable for reaction, requiring a higher
than stoichiometric amount. In general, all reductions are very
clean and high yielding. No intermediate product was isolated
in any reaction.
a
1
Yields refer to those of purified products characterized by IR and H
and 13C NMR spectroscopic data.
The TEM image showed the size of the nanoparticles to be
in the range of 4-6 nm. These nanoparticles in ethylene glycol
were used as such for the reaction. Possibly, ethylene glycol is
providing stability to Cu nanoparticles.
The precise mechanism of this reduction process is not very
clear to us. However, it is predicted that Cu nanoparticles form
CuH by transfer hydrogenation from ammonium formate7c under
the reaction conditions. Although efficient formation of CuH
by reaction of Cu and H2 needed high pressure,7a it is not
unlikely that Cu nanoparticles because of low redox potential5a
and superior reactivity readily form CuH in this procedure. As
Copper nanoparticles were prepared from copper sulfate by
reduction with hydrazine hydrate in ethylene glycol.6 The
identity of Cu nanoparticles was established by transmission
electron microscopy (TEM) and energy dispersive X-ray
spectroscopy (EDS) (Figure 1 and Figure 2).
(6) Zhu, H.; Zhang, C.; Yim, Y. Nanotechnology 2005, 16, 3079–3083.
(7) (a) Burtovyy, R.; Tkacz, M. Solid State Commun. 2004, 131, 169–173.
(b) Mahoney, W. S.; Brestensky, D. M.; Stryker, J. M. J. Am. Chem. Soc. 1988,
110, 291–293. (c) Wiener, H.; Blum, J.; Sasson, Y. J. Org. Chem. 1991, 56,
4481–4486.
6868 J. Org. Chem. Vol. 73, No. 17, 2008

TABLE 2. Reduction of Nitrosobenzene, Phenyl Hydroxylamine,
and Hydrazobenzene by Cu Nanoparticles/HCOONH4
entry
substrate
time (h)
product
yield (%)a
1
2
3
4
Ph-NO
7
7
12
12
Ph-NH2
Ph-NH2
Ph-NH2
Ph-NH2
77
74
13
15
Ph-NHOH
Ph-NdN-Ph
Ph-HN-NH-Ph
a
1
Yields refer to those of purified products characterized by IR and H
and 13C NMR spectroscopic data.
TABLE 3. Comparison of Results of Reductions of Aromatic
Nitro Compounds Using Metallic Cu Powder with Cu
Nanoparticlesa
FIGURE 2. Energy dispersive X-ray spectra of Cu.
SCHEME 3. Proposed Reaction Pathway for Reduction of
Aromatic Nitro Compounds by Cu Nanoparticles/HCOONH4
a
1
Yields refer to those of purified products characterized by IR and H
and 13C NMR spectroscopic data.
To check the efficiency of Cu nanoparticles for this reduction,
a comparison of results of a few representative reactions by
freshly prepared metallic Cu (prepared by the reaction of CuSO4
and Zn dust10) is presented in Table 3. These results clearly
demonstrated much higher efficiency of Cu nanoparticles
compared to metallic Cu.
In conclusion, the present procedure using Cu nanoparticles
and ammonium formate provides a very simple and efficient
methodology for highly chemoselelective reductions of aromatic
nitro compounds. The compatibility of such a wide spectra of
reducible groups was not addressed earlier by other methods
using noble metal nanoparticles,5 and this certainly makes this
procedure unique from others and very useful in organic
synthesis. The cost effectiveness of Cu nanoparticles compared
to other noble metals also adds to its advantage.
CuH is thermally unstable7b it undergoes decomposition under
the reaction conditions to generate Cu and hydrogen to effect
reduction of nitro groups via a hydrogenation process.8
The reduction of aromatic nitro compounds may proceed by
two different routes (Scheme 3).9 In one, the nitro compound
is first reduced to a nitroso compound which further proceeds
to provide the hydroxylamine and finally gives rise to amine.
In the second one, the initially formed nitroso compound may
condense with hydroxylamine to produce the azoxy compound,
which then may undergo further reduction to azo, hydrazo, and
finally to amine. In order to find out the reaction pathway in
the present reaction, we carried out a series of experiments with
these intermediates. When nitrosobenzene and phenyl hydroxyl
amine, obtained by different routes, were subjected to reduction
by this procedure, aniline was obtained in 77% and 74% yields,
respectively (Table 2). However, when azobenzene and hydra-
zobenzene, also obtained separately, were reduced under identi-
cal reaction conditions, aniline was formed only in 13% and
15% yields, respectively. These results clearly suggest that the
azobenzene and hydroazobenzene route is disfavored and the
nitroso and hydroxylamine one is the more probable pathway.
Experimental Section
Representative Experimental Procedure for Reduction of
Aromatic Nitro Compound (entry 2, Table 1). A mixture of
(10) Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R. Vogel’s
Textbook of Practical Organic Chemistry, 5th ed.; Longman Scientific &
Technical: United Kingdom, 1989; p 426.
(11) Moody, C. J.; Pitts, M. R. Synlett 1998, 1028–1030.
(12) Yasuhara, A.; Kasano, A.; Sakamoto, T. J. Org. Chem. 1999, 64, 2301–
2303.
(13) Desai, D. G.; Swami, S. S.; Dabhade, S. K.; Ghagare, M. G. Synth.
Commun. 2001, 31, 1249–1251.
(14) (a) Alcaide, B.; Almendros, P.; Alonso, J. M. Chem. Eur. J. 2003, 9,
5793–5799. (b) Manbeck, G. F.; Lipman, A. J.; Stockland; Jr, R. A.; Freidl,
A. L.; Hasler, A. F.; Stone, J. J.; Guzei, I. A J. Org. Chem. 2005, 70, 244–250.
(8) Bond, G. C. Catalysis by Metals; Academic Press: New York, 1962;
Chapter 11.
(9) Corma, A.; Concepcion, P.; Serna, P. Angew. Chem., Int. Ed. 2007, 46,
7266–7269.
J. Org. Chem. Vol. 73, No. 17, 2008 6869

3-nitrotoluene (137 mg, 1 mmol), Cu nanoparticles (191 mg, 3
mmol) in ethylene glycol (10 mL), and ammonium formate (315
mg, 5 mmol) was heated at 120 °C with stirring for 12 h (TLC)
under argon. Copper particles were filtered off through a short plug
of silica gel. The filtrate was extracted with ethyl acetate. Evapora-
tion of solvent followed by column chromatography over basic
alumina furnished 3-nitroaniline (86 mg, 80%) as a pale yellow
oil. The spectroscopic data (IR, 1H NMR, 13C NMR) of this
compound are in good agreement with those reported.4g
All of these products are known compounds (see refs in Table
1) and were easily characterized by comparison of their spectra
with those reported.
scale reaction, it has been scaled up to gram quantities with
reproducible results.
Acknowledgment. We are pleased to acknowledge financial
support from DST, New Delhi [Grant No. SR/S5/GC-02/2006]
for this investigation. A.S. is thankful to CSIR for his
fellowships.
Supporting Information Available: 1H NMR and 13C NMR
spectra of all the products listed in Table 1 and HRMS analysis
of products in entries 5-12, 14, and 15 in Table 1. This material
is available free of charge via the Internet at http://pubs.acs.org.
This procedure is followed for all of the reactions listed in Table
1. Although the representative procedure is based on millimolar
JO800863M
6870 J. Org. Chem. Vol. 73, No. 17, 2008