Reduction of aromatic nitro compounds to amines using zinc and aqueous chelating ethers: Mild and efficient method for zinc activation

Article abstract of DOI:10.2478/s11696-012-0195-6

A mild, environmentally friendly method for reduction of aromatic nitro group to amine is reported, using zinc powder in aqueous solutions of chelating ethers. The donor ether acts as a ligand and also serves as a co-solvent. Water is the proton source. This procedure is also a new method for the activation of zinc for electron transfer reduction of aromatic nitro compounds. The reduction is accomplished in a neutral medium and other reducing groups remained unaffected. The ethers used are dioxolane, 1,4-dioxane, ethoxymethoxyethane, dimethoxymethane, 1,2-dimethoxyethane, and diglyme.

Full text of DOI:10.2478/s11696-012-0195-6

Chemical Papers 66 (8) 772–778 (2012)
DOI: 10.2478/s11696-012-0195-6
ORIGINAL PAPER
Reduction of aromatic nitro compounds to amines
using zinc and aqueous chelating ethers:
Mild and efficient method for zinc activation
b
aPookot Sunil Kumar*, Kuriya M. Lokanatha Rai
aFMC (I) R&D Centre, Society for Innovation and Development, Indian Institute of Science Campus, 560012 Bangalore, India
bDepartment of Chemistry, University of Mysore, Manasagangotri, 570006 Mysore, India
Received 16 September 2011; Revised 25 March 2012; Accepted 25 March 2012
A mild, environmentally friendly method for reduction of aromatic nitro group to amine is re-
ported, using zinc powder in aqueous solutions of chelating ethers. The donor ether acts as a ligand
and also serves as a co-solvent. Water is the proton source. This procedure is also a new method for
the activation of zinc for electron transfer reduction of aromatic nitro compounds. The reduction
is accomplished in a neutral medium and other reducing groups remained unaffected. The ethers
used are dioxolane, 1,4-dioxane, ethoxymethoxyethane, dimethoxymethane, 1,2-dimethoxyethane,
and diglyme.
c
ꢀ 2012 Institute of Chemistry, Slovak Academy of Sciences
Keywords: reduction, dioxolane, chelating ether, aqueous medium, zinc
Introduction
The selective reduction of aromatic nitro compounds
using iron and dilute acid (Hazlet & Dornfeld, 1944;
Liu et al., 2005) or stannous chloride (Bellamy & Ou,
1984) have been reported as efficient methods. Zinc
has been used in combination with acids/bases (Vogel
et al., 1989) and also with hydrogen donors (Gowda
et al., 2001; Tsukinoki & Tsuzuki, 2001) for the re-
duction of aromatic nitro compounds. However, the
significant disadvantages associated with these meth-
ods include prolonged reaction time, potential halo-
genation, formation of by-products, and incompati-
bility with acid-sensitive groups and other reducible
groups. Here, we report on an efficient method for
the reduction of aromatic nitro compounds (I ) to
amines (II ) using zinc powder in aqueous solutions
of donor ethers (Fig. 1). The ethers used are water-
soluble. The reaction was accomplished at neutral pH
and proceeded with excellent chemo-selectivity and
yields. It avoids the use of an acidic medium and also
serves as a new method for the reduction of nitro com-
pounds.
Aromatic nitro compounds are an important class
of compounds in that they are valuable intermedi-
ates for the preparation of different organic com-
pounds like amines, azo compounds, hydroxyl amines
etc. (Ung et al., 2005). Selective reduction of nitro
compounds (Ram & Ehrenkaufer, 1984; Yuste et al.,
1982; Lyle & Lamittina, 1974; Ho & Wang, 1974;
Onopchenko et al., 1979) is an important synthetic
tool for preparation of aromatic amines in organic
chemistry. Many methods have been reported in the
literature for this reduction, including homogeneous
and heterogeneous catalytic hydrogenation (Welton,
1999; Wasserscheid & Keim, 2000; Sheldon, 2001;
Dupont et al., 2002; Harmon et al., 1973; Johnstone
et al., 1985), reduction using metals (Steines et al.,
2000; Dyson et al., 1999), and electrolytic reduction
(Popp & Schultz, 1962). Recently, catalytic hydro-
genation using hydrogen donors has been widely re-
ported for different substrates (Khan et al., 2003).
*Corresponding author, e-mail: sunilkumarpookot@gmail.com

P. S. Kumar, K. M. Lokanatha Rai/Chemical Papers 66 (8) 772–778 (2012)
773
Fig. 1. Reduction of aromatic nitro compounds using zinc and water-soluble ethers in aqueous medium.
Experimental
General
The nitro compounds used for reduction were pur-
chased from Spectrochem (Mumbai, India), SD fine
chemicals (Mumbai, India), and Sigma–Aldrich (Ban-
galore, India). They were used without purification.
The solvents used were of synthesis grade. They were
used without purification. Zinc used for the reaction
was activated by washing with HCl and then with dis-
tilled water and acetone. The temperatures referred to
in the procedure are temperatures of the oil bath used
for heating.
The progress of the reaction was monitored by
the area normalisation method using a gas chromato-
graphic technique. For this purpose, a Shimadzu GC
gas chromatograph GC 2010 (Kyoto, Japan) with
flame ionisation detector and capillary column (DB-
1; 30 m in length, inner diameter of 0.53 mm) were
used. GC-MS spectra were recorded using a Thermo
Scientific GC-Ion Trap MS (Mumbai, India) (HP-5
capillary column; 30 m in length, inner diameter of
0.25 mm). Melting and boiling points were determined
using melting and boiling point apparatus (Campbell
Electronics, Mumbai, India).
All the products reported here are known com-
pounds and their identity was determined using au-
thentic samples (Sigma–Aldrich, Mumbai, India, and
Spectrochem, Mumbai, India) by GC and GC-MS and
also melting or boiling points from the literature in-
cluding Merck Index.
Fig. 2. Chromatograms of nitrobenzene reduction using Zn
in dioxolane showing the standards: III–VII and the
progress of the reaction after 2 h (a), 5 h (b), and
9 h (c). GC conditions: sample volume, 1.0 µL; solvent,
ethyl acetate; temperatures: injector 300◦C, oven from
100◦C to 250◦C with a ramp of 10◦C min−1, detector
300◦C; vector gas, nitrogen (20 mL min−1).
General procedure for reduction of aromatic
nitro compounds to aromatic amines
on silica gel using ethyl acetate/hexane eluent (ϕr =
1 : 5).
In a typical procedure, water (5 mL) was added to
a stirred solution of the nitro compound (50 mmol)
in water-soluble ether (20 mL). The resulting mix-
ture was stirred for 10 min at laboratory temper-
ature to obtain a clear solution. Zinc (150 mmol)
was added to the solution which was then heated to
70◦C for 7–8 h. Completion of the reaction was mon-
itored by GC. Then, the solution was cooled to lab-
oratory temperature and filtered to remove zinc hy-
droxide and unreacted zinc. The co-solvent was re-
moved under vacuum and the water layer was ex-
tracted with ethyl acetate (100 mL). The organic
layer was evaporated to produce the crude amine,
which was then purified by column chromatography
Results and discussion
Typically, a mixture of aromatic nitro compound
(1 eq.), zinc (from 3 eq. to 3.5 eq.), and water-soluble
ether was heated to 70◦C. The reported reactions were
carried out with water/ether vol. ratio of 1 : 4, but the
reduction of nitrobenzene (III ) was also completed
with a lower proportion of ether. The reaction was
completed with as low as 1 : 4 vol. ratio of ether to
water but, in this case, the reaction mixture was very
thick. Completion of the reaction mixture which could
be well-stirred was achieved with a vol. ratio of ether
to water of 1 : 2. After completion of the reaction, the

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P. S. Kumar, K. M. Lokanatha Rai/Chemical Papers 66 (8) 772–778 (2012)
Fig. 3. Mechanism for generation of electrons (a) and for generation of OH− anion and aromatic nitro reduction (b).

P. S. Kumar, K. M. Lokanatha Rai/Chemical Papers 66 (8) 772–778 (2012)
775
Table 1. Reduction of aromatic nitro compounds to corresponding amines using zinc and aqueous dioxolane (Fig. 1)
Time
h
Yielda
%
B.p. (lit.)
◦C
M.p. (lit.)
◦C
B.p. (obs.) M.p. (obs.)
Entry
1
Nitro compound
Product
◦C
◦C
9
5
90
90
184b
–
183
–
2
3
–
57c
–
–
57
7
88
–
188d
186
4
5
6
7
5
10
10
5
85
87
85
95
–
72e
15f
–
–
72
12
–
–
–
208g
199h
208
196
–
–
8
9
5
7
85
82
–
–
48–50i
–
–
47
222–229j,k
221
10
11
10
80
81
–
180–183l
–
179
5
210–212m
–
211
–
12
11
75
–
104–106n
–
100

776
P. S. Kumar, K. M. Lokanatha Rai/Chemical Papers 66 (8) 772–778 (2012)
Table 1. (continued)
Time
h
Yielda
%
B.p. (lit.)
◦C
M.p. (lit.)
◦C
B.p. (obs.)
◦C
M.p. (obs.)
◦C
Entry
13
Nitro compound
Product
7
88
81
203–204o
–
201
–
14
11
–
98–99p
–
96
a) Isolated yield; b) O’Neil (2006a); c) Sarmah (2003); d) O’Neil (2006b); e) O’Neil (2006c); f ) Staiger & Miller (1959); g) O’Neil
(2006d); h) O’Neil (2006e); i) O’Neil (2006f); j ) Rinderknecht et al. (1953); k) isolated as hydrochloride salt; l) Ashley et al. (1960);
m) Abiraj et al. (2005); n) Kijima et al. (1984); o) O’Neil (2006e); p) Simpson et al. (1945).
solids were removed by filtration and the amine ex-
tracted using ethyl acetate. The crude amine obtained
by evaporation of ethyl acetate was purified by column
chromatography on silica gel using hexane/ethyl ac-
etate ((ϕr = 5 : 1) as the eluent. The yields of isolated
amine were in the range of 75–90 %.
In order to understand the mechanism involved,
some probing experiments were performed using ni-
trobenzene as the substrate. Initial trials were carried
out using zinc in an aqueous solution of dioxolane or
1,4-dioxane. In these solvents, phenylamine (aniline)
was formed in good yields. Substitution of dioxolane
with other water-soluble solvents like methanol, ace-
tonitrile, DMF, and DMSO did not lead to the forma-
tion of any product. In the absence of water, no reac-
tion was observed. The nitro compound remained un-
affected. The reaction was initiated immediately and
completed with un-activated zinc also.
diphenyldiazene (azobenzene) (VI ) along with a mi-
nor peak of aniline (VII ) (Fig. 3). The peaks of ni-
trosobenzene, azoxybenzene, azobenzene, and aniline
were confirmed by comparison with authentic com-
pounds. As the reaction progressed, the peaks of
nitroso-, azoxy-, and azo-compounds were observed to
be slowly converted to aniline. Aniline was isolated in
good yields at the end of the reaction. Based on the
mechanism for the reduction published in the litera-
ture (Ung et al., 2005), a plausible mechanism is given
in Fig. 3.
The ability of zinc ions to form complexes with
chelating ethers activates the zinc metal to electron
transfer. The aromatic nitro compounds are reduced
to amines by electron transfer reduction. The hydroxyl
ions generated in the solution can react with zinc com-
plexes to form zinc hydroxide (illustrated by the use
of diethoxymethane in Fig. 3a).
To verify the function of ether, a few trials
were carried out using other aqueous miscible ethers
as solvents. The ethers used were diglyme, 1,2-
dimethoxyethane, ethoxymethoxyethane (diethoxy-
methane), and dimethoxymethane. These solvent mix-
tures also provided aniline in good yields. A control
experiment using a 4 : 1 vol. ratio of THF/water mix-
ture gave poor conversion. These results confirm that
ethers with good chelating properties are required for
progress of the reaction.
The advantages of this method are that corro-
sive media are avoided in the reduction, reduction
of the nitro group in the presence of other reducible
groups is selective, environmentally friendly solvents
are used, use of hydrogen under pressure and ex-
pensive catalysts are avoided. The amine can eas-
ily be recovered. During the reduction, functional
groups such as amide, ester, chloro-, methoxy-, alkene,
and keto- groups labile for reduction remained unaf-
fected.
The reduction of aromatic nitro compounds with
different functional groups was studied using aqueous
dioxolane as the solvent (Table 1). The temperature
GC chromatograms
of the reaction was maintained at 70–75◦
On chromatograms, the front peaks are the solvent
peaks which are not integrated.
C.
The significance of the above procedure with var-
ious ether/water mixtures is summarised (Table 2).
p-Nitrophenol was used as the substrate. The exper-
iments were performed at 70◦C. The same procedure
was followed for all the ethers. All reactions were com-
pleted within 7–8 h. In aqueous THF, the product was
isolated in low yield.
To determine the mechanistic pathway of the re-
duction precisely, samples were periodically collected
from the reaction mixture and analysed by GC. Ini-
tially, GC monitoring (Fig. 2) of the reaction showed
the formation of nitrosobenzene (IV ), oxido-phenyl-
phenyliminoazanium (azoxybenzene) (V ), and (E)-

P. S. Kumar, K. M. Lokanatha Rai/Chemical Papers 66 (8) 772–778 (2012)
777
Table 2. Reduction of p-nitrophenol to p-amino phenol (Fig. 1)
using zinc and aqueous ethers (ϕr = 1 : 4)
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Ho, T. L., & Wang, C. M. (1974). Reduction of aromatic nitro
compounds by titanium(III) chloride. Synthesis, 1974, 45.
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Entry
1
Ether
Yielda/%
88
Johnstone, R. A. W., Willby, A. H., & Entwistle, I. D. (1985).
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2
86
3
4
88
85
5
6
87
85
Kijima, M., Nambu, Y., Endo, T., & Okawara, M. (1984). Selec-
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7
3
a) Isolated yield.
Conclusions
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By using zinc in aqueous solutions of chelating di-
ethers, an environmentally benign, efficient, simple,
economical, and chemo-selective method for the re-
duction of aromatic nitro compounds to amino com-
pounds was reported. This method is suitable for use
with other reducible groups and the yield of the reac-
tion is not affected by the structure of the ether.
Acknowledgements. The authors express their gratitude to
the FMC Corporation for providing the opportunity and sup-
port for them to do this work.
O’Neil, M. J. (2006f). Merck Index (pp. 6398). Whitehouse Sta-
tion, NY, USA: Merck Research Laboratories.
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