Oxygen as moderator in the zinc-mediated reduction of aromatic nitro to azoxy compounds

Article abstract of DOI:10.1016/j.tetlet.2009.02.122

A simple and useful protocol for the reduction of nitro arenes to their corresponding azoxy derivatives by employing zinc and NH₄Cl in a mixture of [bmim][BF₄] and water is described. The selective reduction of nitro to azoxy is attributed to the hitherto unknown moderating effect of oxygen on zinc metal.

Full text of DOI:10.1016/j.tetlet.2009.02.122

Tetrahedron Letters 50 (2009) 3394–3396
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Oxygen as moderator in the zinc-mediated reduction of aromatic
nitro to azoxy compounds
*
Faiz Ahmed Khan , Ch. Sudheer
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and useful protocol for the reduction of nitro arenes to their corresponding azoxy derivatives by
employing zinc and NH4Cl in a mixture of [bmim][BF4] and water is described. The selective reduction of
nitro to azoxy is attributed to the hitherto unknown moderating effect of oxygen on zinc metal.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 10 January 2009
Revised 9 February 2009
Accepted 18 February 2009
Available online 21 February 2009
Dedicated to Professor Dr. Hans-Ulrich
Reissig on the occasion of his 60th birthday
Aromatic azoxy compounds are of immense importance as
materials for electronic devices because of their liquid crystalline
properties.1 ‘Williams domain’, an important phenomenon
describing the electrooptic property of liquid crystals, was estab-
lished with azoxyarenes by Williams.2 Azoxyarenes have also been
utilized as dyes, analytical reagents, reducing agents, stabilizers,
and polymerization inhibitors.3 Azoxy compounds can be prepared
from their corresponding amines,4 hydroxylamines,5 nitroso
hydroxylamine ammonium salts,6 and azo,7 nitro,8–10 and nitroso
compounds.11,12 The aforementioned methods require reducing
agents, oxidizing agents, or UV light.
Methods to obtain azoxyarenes from nitroarenes include heat-
ing with alcoholic KOH,13 sodium alkoxide,14 or Zn/NaOH,15 reduc-
tion with NaBH4,16 LiAlH4,17 or sodium arsenite,18 treatment with
magnesium,19 samarium,20 or thallium metal21 in alcohol, catalytic
reduction over palladium,22 alkaline reduction with phosphine23 or
glucose,24 and electrochemical reduction.25 Of all the methods
known for the reduction of nitroarenes to their corresponding
azoxy derivatives, a few involve interesting plausible mechanistic
explanations.26,8b,c
In continuation of our work on zinc-mediated reductions of
nitroarenes in ionic liquids,27 we herein disclose an efficient meth-
odology for the conversion of nitro compounds to their corre-
sponding azoxy derivatives. Based on the observation from the
previous work that the ionic liquids be completely free from dis-
solved oxygen during the zinc-mediated reduction of nitro arenes
to corresponding amines,27 we carried out the reduction of nitro
compounds in ionic liquids under an atmosphere of oxygen. These
conditions selectively yielded the azoxy compounds in excellent
yields.
When no efforts were made to remove the dissolved oxygen in
the ionic liquids during the zinc-mediated nitro reductions, we ob-
tained a mixture of products: azoxy, azo, and hydrazoarenes,
wherein azoxyarenes were the major products. The reactions were
found to be more sensitive in [bmim][BF4] than in [bmim][PF6]
(bmim = 1-butyl-3methylimidazolium). We found this effect of
oxygen on the outcome of the reaction very interesting. Although
the deleterious effects of oxygen on the metal-mediated reactions
are well known,28 we did not come across any report in the litera-
ture wherein oxygen is known to moderate zinc metal-mediated
reductions.29 This observation interested us to check if we could
use oxygen to obtain exclusively the azoxyarenes without the for-
mation of azo, hydrazo, or amine derivatives.
To select a solvent system that would facilitate the exclusive
formation of azoxyarenes from aromatic nitro compounds, various
solvent systems were screened. The reduction of p-nitrotoluene
was carried out using zinc metal (3 equiv) and NH4Cl (3 equiv) in
a mixture of solvent–H2O (10:1). From these experiments (Table 1),
[bmim][BF4] emerged as the solvent of choice for the formation
of azoxyarenes upon the zinc-mediated reduction of nitroarenes.
Using other solvents (Table 1, entries 4–8) resulted in the forma-
tion of a mixture of products. After the selection of a solvent, we
wanted to check if other metals were better than zinc in affording
azoxy arenes from nitroarenes under similar reaction conditions.
The reduction of p-nitrotoluene was carried out with various met-
als, and the results are illustrated in Table 2.
Nitro reductions were carried out using a metal (3 equiv), NH4Cl
(3 equiv) in [bmim][BF4]:H2O (10:1) at room temperature in an
atmosphere of oxygen (bubbling). Reduction with zinc over 26 h
(Table 2, entry 1) afforded a mixture of azoxy and azo compounds
(95:5). Reducing the time to 12 h resulted in the exclusive forma-
tion of an azoxy compound but with 80% conversion of the starting
material (Table 2, entry 2). When samarium, tin, and indium were
used for the reduction of p-nitrotoluene, the conversions were very
* Corresponding author. Tel.: +91 512 2597864; fax: +91 512 2597436.
E-mail address: faiz@iitk.ac.in (F.A. Khan).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.122

F. A. Khan, Ch. Sudheer / Tetrahedron Letters 50 (2009) 3394–3396
3395
Table 1
Table 3
Product distribution during zinc-mediated reduction of p-nitrotoluene in different
Zinc-mediated reduction of various nitroarenes to azoxyarenes
solvents
O
O
Zn, NH4Cl, O2
Ar NO2
Ar N N Ar
Ar NO2
Ar
N
N
Ar + Ar
+
N N Ar
bmimBF4:H2O (10:1)
r.t.
1a-l
2a-l
Azoxy
Azo
Entry
Substrate
R
Time (h)
Yield (%)
Ar NH2
Amine
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1 g
1 h
1i
p-Me
p-OMe
o-Me
p-Cl
m-Cl
p-OAc
H
16
16
18
15
16
17
16
16
18
20
16
16
96
91
88
90
86
78
94
82
92
90
86
94
Entry
Solvent
Temperature,
Product distribution
(azoxy/azo/amine)
Yielda (%)
time (°C, h)
1
2
3
4
5
6
7
8
bmimBF4
bmimBF4
bmimBF4
bmimPF6
THF
DMSO
MeCN
Acetone
10, 12
100/0/0
100/0/0
100/0/0
79/0/21
60/10/30
70/20/10
70/30/0
90/10/0
90 (80)
91 (70)
88 (50)
95 (40)
86 (60)
91
0, 2 then 25, 9
À10, 12
15, 24
10, 12
10, 3
p-I
o-OMe
o-OBn
p-O-allyl
m-Me
10
11
12
1j
1 k
1 l
10, 13
10, 15
84 (30)
92 (55)
4 equiv of Zn and 3 equiv of NH4Cl were used.
Reactions were carried out with 3 equiv of Zn and 3 equiv of NH4Cl in solvent–H2O
(10:1) under an atmosphere of oxygen.
a
At the outset, we thought that the reason for the selective for-
mation of azoxy derivatives under an oxygen atmosphere could
be attributed to the moderating effect of oxygen on zinc metal.
We wanted to rule out other possibilities wherein nitro is first re-
duced to amino and then oxidized to azoxy. To check on this pos-
sibility, two experiments were carried out. Subjecting p-toluidine
to the conditions that were used for the conversion of nitroarenes
to their azoxy derivatives resulted in the complete recovery of the
starting material. In the second control experiment, p-nitrotoluene
was reduced to p-toluidine following the protocol reported previ-
ously.27 Once the conversion to p-toluidine was complete, oxygen
was bubbled through the reaction mixture, but p-toluidine did not
undergo any oxidation (Scheme 1). This observation rules out the
possibility that a reagent system generated in situ during the
reduction of nitro to amino can be responsible for the selective for-
mation of azoxy derivatives. Based on these results, the selective
formation of the azoxy derivatives was attributed to the moderat-
ing effect of oxygen on zinc.
The methodology was extended to the synthesis of azoxycr-
owns. Crowns, wherein the azoxy moiety is part of the crown,
are known to be ion carriers. The existing methods for the synthe-
sis of these compounds would require a tedious chromatography
to separate the products from the mixture.30 Applying the present
procedure for the cyclization of bis-nitro derivatives 5a,b resulted
in the selective formation of azoxy crowns 6a,b (Scheme 2) in
yields better or comparable to that reported.30
Numbers in parentheses are the percentage conversions of nitroarenes.
low (Table 2, entries 3, 4, and 6) and using lead as the metal for ni-
tro reduction resulted in a complete recovery of the starting mate-
rial without any conversion of the nitroarene (Table 2, entry 5).
Using 4 equiv of zinc resulted in the exclusive formation of azoxy-
arene with a complete conversion of the nitro compound.
The optimized condition, that is, Zn (4 equiv), NH4Cl (3 equiv) in
[bmim][BF4]:H2O (10:1) at room temperature in an atmosphere of
oxygen, was employed for a variety of nitroarenes which yielded
azoxyarenes in good to excellent yields (Table 3). The reaction con-
ditions were tolerant to various functional groups such as chloro,
iodo, acetate, O-allyl, and O-benzyl. After the completion of the
reaction, products were separated by extracting with 30–50%
EtOAc in hexane. The crude products thus obtained were pure
and did not require any further purification in general. However,
the azoxyarenes were filtered through a short pad of silica gel be-
fore recording their NMR spectra. The products were confirmed by
comparing the 1H NMR spectra (400 MHz) with those reported in
the literature.8 The ionic liquids used for the reaction were recy-
cled. After the extraction of the product, CH2Cl2 was added to the
reaction mixture containing [bmim][BF4] and inorganic impurities.
The suspension was filtered through a Whatman filter paper to re-
move the insoluble impurities, and the ionic liquids were reused
after removing CH2Cl2 completely on a rotavapor followed by vac-
uum drying.
In summary, we have described a novel, efficient method for the
conversion of nitro compounds to their corresponding azoxy deriv-
atives. This method was applied to the preparation of a variety of
aromatic azoxy arenes including azoxy crowns. The ionic liquid
used [bmim][BF4] was recycled without any effect on the outcome
of the reaction.
Table 2
Comparison of product distribution during reduction of p-nitrotoluene with various
metals
Entry
M
Time (h)
Product distribution
(azoxy/azo/hydrazo)
Yielda (%)
1
2
3
4
5
6
7
Zn
Zn
Sm
Sn
Pb
In
26
12
12
72
72
68
16
95/5/0
100/0/0
100/0/0
69/0/39b
—
96
93 (80)
85 (20)
81 (25)
—
NO2
Me
NH2
Zn, HCOONH4
O2
no reaction
100/0/0
100/0/0
62 (40)
94c
bmimBF4, H2O
inert atm., 9 h
14 h
Zn
Me
p-toluidine
3 equiv of metal and 3 equiv of NH4Cl were used.
a
Numbers in parentheses are the percentage conversions of nitroarenes.
Hydrazo = Ar–NH–NH–Ar.
4 equiv of Zn was used.
b
c
Scheme 1.

3396
F. A. Khan, Ch. Sudheer / Tetrahedron Letters 50 (2009) 3394–3396
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General procedure for the synthesis of azoxy compounds: To an
oxygen purged solution of nitroarene (0.5 mmol) in [bmim][BF4]
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Acknowledgments
We thank the Department of Science and Technology (DST),
New Delhi, for financial assistance. F.A.K. acknowledges the DST
for a Swarnajayanti Fellowship.
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