Reduction of nitroarenes to azoxybenzenes by NaOH-PEG 400

Article abstract of DOI:10.1080/00397911.2011.555052

The reduction of nitroarenes to azoxybenzenes by NaOH-PEG 400 in benzene is described. The protocol is facile, economical, and effective.

Full text of DOI:10.1080/00397911.2011.555052

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Reduction of Nitroarenes to
Azoxybenzenes by NaOH-PEG 400
Yufang Liu a , Bo Liu b , Ailing Guo a , Zhenming Dong a , Shuo Jin a &
Yun Lu c
a School of Chemistry and Chemical Engineering, Shanxi University,
Taiyuan, China
b School of Science, Beijing Jiaotong University, Beijing, China
c Department of Chemistry, Southern Illinois University–Edwardsville,
Edwardsville, Illinois, USA
Accepted author version posted online: 19 Dec 2011.Published
online: 09 Apr 2012.
To cite this article: Yufang Liu , Bo Liu , Ailing Guo , Zhenming Dong , Shuo Jin & Yun Lu (2012):
Reduction of Nitroarenes to Azoxybenzenes by NaOH-PEG 400, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 42:15, 2201-2206
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Synthetic Communications1, 42: 2201–2206, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.555052
REDUCTION OF NITROARENES TO AZOXYBENZENES
BY NaOH-PEG 400
Yufang Liu,1 Bo Liu,2 Ailing Guo,1 Zhenming Dong,1
Shuo Jin,1 and Yun Lu3
1School of Chemistry and Chemical Engineering, Shanxi University,
Taiyuan, China
2School of Science, Beijing Jiaotong University, Beijing, China
3Department of Chemistry, Southern Illinois University–Edwardsville,
Edwardsville, Illinois, USA
GRAPHICAL ABSTRACT
Abstract The reduction of nitroarenes to azoxybenzenes by NaOH-PEG 400 in benzene is
described. The protocol is facile, economical, and effective.
Keywords Azoxybenzenes; benzene; nitroarenes; poly(etheylene glycol 400); sodium
hydroxide
INTRODUCTION
Conversion of nitroarenes into the corresponding azoxybenzenes can be
carried out with a variety of reducing reagents such as alkaline metal borohydrides,[1]
sodium arenetellurolate,[2] phosphine,[3] InBr3-Et3SiH,[4] and metals such as
samarium,[5] thallium,[6] and nickel.[7] However, most of these methods suffer from
drawbacks such as high costs, lengthy reactions, poor yields, or inconvenient workup
procedures; therefore, there is a need for a facile, economical, and effective synthetic
procedure for the preparation of azoxybenzenes.
The reduction of aldehydes and ketones to the corresponding alcohols by
KOH-isopropanol has been recently reported, in which isopropanol is used as a
hydrogen source and solvent. This protocol is unprecedented, simple, economical,
and effective.[8] Thus, we attempt the reduction of nitroarenes to azoxybenzenes
by the analogical reducing system. Here, we first designed the reduction of nitro-
arenes by NaOH-poly(ethylene glycol 400) (PEG 400) in benzene, and the corre-
sponding azoxybenzenes were obtained in moderate to good yields (Scheme 1).
Received December 22, 2010.
Address correspondence to Bo Liu, School of Science, Beijing Jiaotong University, Beijing 100044,
China. E-mail: boliu413@yahoo.com.cn
2201

2202
Y. LIU ET AL.
Scheme 1. Reduction of nitroarenes to azoxybenzenes.
Aprotic benzene was selected as a solvent to reduce the solvent effects of alcohol on
the reduction; the widely available and inexpensive PEG 400 could not only play a
role as hydrogen source but also transfer NaOH into the organic phase and promote
the reductions as a phase-transfer catalyst similar to crown ethers.[9]
RESULTS AND DISCUSSION
At the beginning of our work, we chose to study the reduction of m-bromoni-
trobenzene as a model reaction. The effects of the reaction temperature and the
amounts of PEG 400 and NaOH on the reaction were investigated, and the results
from our optimization studies are listed in Table 1.
Initially, both the reaction rates and yields increased with increasing amounts
of NaOH (entries 1-1 and 1-2); however, beyond a certain value, it appeared that
increasing the amounts of NaOH had no effect on the reaction (entry 1-3).
While maintaining the optimized amount of NaOH, we found that no reaction
(NR) took place in the absence of PEG 400 (entry 1-4). By increasing the amount of
PEG 400 to 0.5 mmol (entry 1-2), a good yield (80%) was achieved. When the
amount of PEG 400 was further increased to 0.6 mmol (entry 1-6), only 74% yield
was observed, which may be the result of further reductions of the azoxybenzenes
by a superfluous hydrogen source.
The effects of reaction temperature were also investigated (entries 1-2, 1-7, and
1-8). We found that no reaction (NR) occured when the temperature was not higher
than 60 ꢀC (entry 1-7), but the reaction yields dramatically increased with increasing
temperature, indicating the reaction has a high activation energy.
The reductions of a variety of nitroarenes were studied under the optimal con-
ditions, and the corresponding azoxybenzenes were obtained in moderate to good
Table 1. Optimization of reaction conditionsa
Entry
NaOH (mmol)
PEG 400 (mmol)
Temperature (ꢀC)
Time (h)
Yield (%)b
1-1
1-2
1-3
1-4
1-5
1-6
1-7
1-8
5
8
0.5
0.5
0.5
0
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
60
4
1
63
80
10
8
1
80
12
1
NR
69
8
0.4
0.6
0.5
0.5
8
1
74
8
12
4
NR
57
8
70
aReaction conditions: m-bromonitrobenzene (1 mmol), benzene (20 mL).
bIsolated yields of m,m0-dibromoazoxybenzene after recrystallization.

SYNTHESIS OF AZOXYBENZENES
2203
Table 2. Reductions of nitroarenes into the corresponding azoxybenzenes by NaOH-PEG
400 in benzenea
Entry
R
Nitroarenes Reaction time (h) Azoxybenzenes Yield (%)b
2-1
2-2
2-3
2-4
2-5
2-6
2-7
2-8
2-9
2-10
2-11
2-12
H
m-Cl
p-Cl
1a
1b
1c
1d
1e
1f
5
3
5
1
3
3
5
4
4
2
8
8
2a
2b
2c
2d
2e
2f
90
85
44
80
43
76
40
50
86
44d
50
64
m-Br
p-Br
m-I
p-I
1g
1h
1i
2g
2h
2i
o-CH3
m-CH3
p-CH3
p-OCH3
c
1j
1k
—
2k
2l
p-OCH2CH3 1l
aReaction conditions: nitroarenes (1 mmol), NaOH (8 mmol), and PEG 400 (0.5 mmol) in
benzene (20 mL) at reflux temperature.
bIsolated yields of azoxybenzenes after recrystallization.
cNo p,p0-dimethylazoxybenzene was obtained.
dYield refers to p,p0-dinitrobibenzyl.
yields (Table 2). These results suggest that the locations of substituent groups play an
important role in determining the reduction efficiencies. Nitrobenzene and meta-
substituted analogs were reduced efficiently, while para-substituted analogs were
reduced in lower yields, which may be due to the presence of nucleophilic substitution
side reactions in para-substituted nitroarenes. In addition, we found that the
reactions of o-chloronitrobenzene, o-bromonitrobenzene, and o-iodonitrobenzene
gave very complicated mixtures that were difficult to separate (not listed in Table 2;
detailed studies are under way). For p-nitrotoluene (entry 2-10), no p,p0-
dimethylazoxybenzene could be isolated, whereas p,p0-dinitrobibenzyl was obtained
with 44% yield, which is because p-nitrotoluene (which possesses weakly acidic
a-H) could spontaneously disproportionate in strongly basic medium to the reduced
species, its radical anion, and as oxidized form p,p0-dinitrobibenzyl.[10]
In conclusion, we have developed a new method for synthesis of azoxybenzenes
by the reduction of the corresponding nitroarenes with NaOH-PEG 400 in benzene
at reflux temperature. The simple experimental procedure, the use of economically
viable reagents, and the high efficiency of the reactions are advantages of this proto-
col, making this method useful for large-scale production of azoxybenzenes.
EXPERIMENTAL
All the reagents were obtained from commercial sources and used without
further purification. Melting points of the compounds were measured using a Sanyo-
Callenksmp apparatus and were uncorrected. The infrared (IR) spectra were recorded
on a Perkin-Elmer 1700 spectrometer. 1H NMR spectra in CDCl3 were recorded on a
Bruker DLX 300-MHz spectrophotometer. Elemental analysis was obtained from a
VazioE elemental analyzer.

2204
Y. LIU ET AL.
General Procedure for Synthesis of Azoxybenzenes
Nitroarenes (1 mmol) were added to a mixture of NaOH (8 mmol) and PEG
400 (0.5 mmol) in 20 mL benzene in a flask equipped with a condenser. The
resultant solutions were magnetically stirred at reflux temperature until the
nitroarenes were consumed, monitored by thin-layer chromatography (TLC).
The solutions were filtered, rotary evaporated, and precipitated in water. The
crude products were isolated by filtration and further purified by recrystallization
in ethanol.
Compound 2a
Mp 35–36 ꢀC (lit.[11] 35 ꢀC); 1H NMR (300 MHz, CDCl3): d ¼ 7.40–7.54 (m, 6H),
8.05–8.32 (m, 4H); IR, t (KBr disc): 1572, 1474, 1425, 1329, 750, 670 cmꢁ1
.
Compound 2b
1
Mp 97–98 ꢀC (lit.[6] 96–97 ꢀC); H NMR (300 MHz, CDCl3): d ¼ 7.36–7.56 (m,
4H), 7.99 (d, J ¼ 7.5 Hz, 1H), 8.19 (d, J ¼ 8.4 Hz, 1H), 8.25 (s, 1H), 8.30 (s, 1H); IR, t
(KBr disc): 1556, 1470, 1421, 1302, 783 cmꢁ1
.
Compound 2c
1
Mp 154–156 ꢀC (lit.[6]156–157 ꢀC); H NMR (300 MHz, CDCl3): d ¼ 7.50 (dd,
J ¼ 9, 9 Hz, 4H), 8.19 (d, J ¼ 8.7 Hz, 2H), 8.28 (d, J ¼ 9 Hz, 2H); IR, t (KBr disc):
1583, 1481, 1404, 1323, 831 cmꢁ1
.
Compound 2d
Mp 111–113 ꢀC (lit.[6] 109–110 ꢀC); 1H NMR (300 MHz, CDCl3): d ¼ 7.36–7.45
(m, 2H), 7.56 (d, J ¼ 9.9 Hz, 1H), 7.73 (d, J ¼ 9.9 Hz, 1H), 8.06 (d, J ¼ 0.9 Hz, 1H),
8.09 (d, J ¼ 1.2 Hz, 1H), 8.24 (s, 1H), 8.29 (s, 1H); IR, t (KBr disc): 1553, 1472, 1420,
1298, 781 cmꢁ1
.
Compound 2e
1
Mp 171–173 ꢀC (lit.[5]173–175 ꢀC); H NMR (300 MHz, CDCl3): d ¼ 7.66 (dd,
J ¼ 9, 9 Hz, 4H), 8.11 (d, J ¼ 8.7 Hz, 2H), 8.21 (d, J ¼ 9 Hz, 2H); IR, t (KBr disc):
1575, 1465, 1398, 1319, 826 cmꢁ1
.
Compound 2f
Mp 120–121 ꢀC (lit.[6] 118–119 ꢀC); 1H NMR (300 MHz, CDCl3): d ¼ 7.18–7.27
(m, 2H), 7.71 (d, J ¼ 7.8 Hz, 1H), 7.89 (d, J ¼ 7.8 Hz, 1H), 8.08 (d, J ¼ 9 Hz, 1H), 8.25
(d, J ¼ 8.1 Hz, 1H), 8.55 (s, 1H), 8.63 (s, 1H); IR, t (KBr disc): 1545, 1470, 1418,
1294, 783 cmꢁ1
.

SYNTHESIS OF AZOXYBENZENES
2205
Compound 2g
1
Mp 205–207 ꢀC (lit.[5] 208–210 ꢀC); H NMR (300 MHz, CDCl3): d ¼ 7.78 (dd,
J ¼ 8.7, 12.9 Hz, 4H), 7.87 (d, J ¼ 8.4 Hz, 2H), 7.98 (d, J ¼ 8.4 Hz, 2H); IR, t (KBr
disc): 1572, 1468, 1393, 1321, 829 cmꢁ1
.
Compound 2h
Mp 59–60 ꢀC (lit.[11] 60 ꢀC); 1H NMR (300 MHz, CDCl3): d ¼ 2.37 (s, 3H), 2.52
(s, 3H), 7.28–7.39 (m, 6H), 7.67 (d, J ¼ 7.5 Hz, 1H), 8.03 (d, J ¼ 9.3 Hz, 1H); IR, t
(KBr disc): 1485, 1420, 1381, 1329, 760 cmꢁ1
.
Compound 2i
1
Mp 35–37 ꢀC (lit.[6] 33–35 ꢀC); H NMR (300 MHz, CDCl3): d ¼ 2.41 (s, 3H),
2.44 (s, 3H), 7.18 (d, J ¼ 7.2 Hz, 1H), 7.33–7.38 (m, 3H), 7.96-8.09 (m, 4H); IR, t
(KBr disc): 1603, 1493, 1458, 1414, 1306, 787 cmꢁ1
.
Compound 2k
1
Mp 115–116 ꢀC (lit.[6] 116.5–118.5 ꢀC); H NMR (300 MHz, CDCl3): d ¼ 3.89
(s, 6H), 6.97 (dd, J ¼ 7.2, 8.7 Hz, 4H), 8.27 (dd, J ¼ 9, 8.7 Hz, 4H); IR, t (KBr disc):
1595, 1499, 1411, 1387, 1300, 1252, 839 cmꢁ1
.
Compound 2l
Mp 137–139 ꢀC; 1H NMR (300 MHz, CDCl3): d ¼ 1.43–1.47 (m, 6H),
4.07–4.14 (m, 4H), 6.95 (dd, J ¼ 5.7, 8.7 Hz, 4H), 8.24 (dd, J ¼ 9, 11.1 Hz, 4H); IR,
t (KBr disc): 1598, 1500, 1473, 1411, 1390, 1300, 1256, 845 cmꢁ1; Anal. calcd. for
C16H18N2O3: C, 67.12; H, 6.34; N, 9.78. Found: C, 66.86; H, 6.46; N, 9.69.
ACKNOWLEDGMENT
The authors are grateful to the National Science Foundation of China (Liu,
No. 21072019) for the support of this work.
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