The selective reduction of nitroarenes to N-arylhydroxylamines using Zn in a CO2/H2O system

Article abstract of DOI:10.1039/b906283a

Nitroarenes are reduced to the corresponding N-arylhydroxylamines with high selectivity using Zn dust in a CO₂/H₂O system under mild conditions. The yield of N-phenylhydroxylamine from nitrobenzene is 88% when the reaction is carried out at 25 °C for 1.5 hours with a Zn to nitrobenzene molar ratio equal to 3 under 0.1 MPa CO₂. Other nitroarenes, which contain reducible functionality other than a nitro group, are also reduced to the corresponding N-arylhydroxylamines with yield from 88% to 99%. The process fully removes the need to use NH₄Cl and is environmentally benign. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b906283a

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The selective reduction of nitroarenes to N-arylhydroxylamines using Zn in
a CO2/H2O system†
Shijuan Liu,a,b Yanhua Wang,a Jingyang Jiang*a and Zilin Jina
Received 31st March 2009, Accepted 29th May 2009
First published as an Advance Article on the web 25th June 2009
DOI: 10.1039/b906283a
Nitroarenes are reduced to the corresponding N-arylhydroxylamines with high selectivity using
Zn dust in a CO2/H2O system under mild conditions. The yield of N-phenylhydroxylamine from
nitrobenzene is 88% when the reaction is carried out at 25 ◦C for 1.5 hours with a Zn to
nitrobenzene molar ratio equal to 3 under 0.1 MPa CO2. Other nitroarenes, which contain
reducible functionality other than a nitro group, are also reduced to the corresponding
N-arylhydroxylamines with yield from 88% to 99%. The process fully removes the need to use
NH4Cl and is environmentally benign.
the application of this environmentally benign system.12 In our
previous work, the reductions of nitroarenes to aromatic amines
Introduction
N-Arylhydroxylamines are useful intermediates in the synthesis
of fine chemicals1 and pharmaceuticals.2 These amines are
usually prepared by selective reduction of the corresponding
nitroarenes. N-Phenylhydroxylamine (PHA) was first prepared
by the zinc reduction of nitrobenzene (NB) more than a hun-
dred years ago3 and the method using Zn dust in aqueous NH4Cl
solution was modified into a conventional protocol.4 Many other
methods for the preparation of N-phenylhydroxylamine have
been reported, which include catalytic hydrogenation,5 catalytic
hydrogen transfer,6 reduction by sulfide7 or by borohydride,8
electrolytic reduction9 and biocatalysis.10 The catalytic hydro-
genation is a clean method, but over reduction of nitroarenes to
aromatic amines is a problem. The catalytic hydrogen transfer
reduction consumes various reagents as a hydrogen source, such
as formic acid or hydrazine, in the presence of metal catalysts
(Pd, Rh and Raney Ni), many of which are very expensive.
The reduction by sulfide produces much wastewater and the
reduction by borohydride involves the use of poisonous elements
Se, Te, Sb or Bi. Furthermore, the electrolytic reduction and
biocatalyst methods are costly. The traditional method using
Zn dust for the preparation of N-arylhydroxylamines shows the
advantages of mild reaction conditions, good product selectivity
and low cost. Nevertheless, it has the drawbacks that large
amount of NH4Cl is consumed and a lot of wastewater is formed.
In view of environmental concerns, it is important to develop an
efficient method, which avoids using NH4Cl.
using Fe in a CO2/H2O system have been developed,13 and
the same reaction using Zn dust as reducing agent has been
also reported by Jiang et al.14 The product formed in the zinc
reduction of nitrobenzene is dependent on the pH value of the
reaction medium. For example, azoxybenzene is obtained from
nitrobenzene in basic solution, whereas N-phenylhydroxylamine
is obtained using Zn in aqueous NH4Cl, a weak acidic solution.
It is noteworthy that the acidity of a CO2/H2O system is close to
that of aqueous NH4Cl solution, so the reduction of nitroarenes
to N-arylhydroxylamines using Zn in a CO2/H2O system is very
promising. In this manuscript the investigation results in this
subject are presented.
Results and discussion
Firstly, the reduction of nitrobenzene to N-phenylhydroxy-
lamine was tested in a 75 mL autoclave. The effects of different
reaction conditions on the reduction were studied and the results
were shown in Table 1. It should be pointed out that only trace
reduction took place in the absence of CO2 (entry 1), and the
reaction could be accelerated dramatically with the charge of
0.1 MPa CO2 (entry 2). Therefore, CO2 plays a crucial role in
the reaction. At a reaction temperature of 40 ◦C, the yield of
N-phenylhydroxylamine reached 76% with a CO2 pressure of
0.5 MPa (entry 3). With a further increase of CO2 pressure,
the amount of aniline (AN), the side product due to the full
reduction of nitrobenzene, increased and the reaction selectivity
to N-phenylhydroxylamine decreased (entries 4–6). When the
reaction was run with a Zn to nitrobenzene molar ratio equal
to 3 and 0.5 MPa CO2 pressure for 3 hours, the yield of
N-phenylhydroxylamine reached the maximum at 40 ◦C within
the temperature range from 20 ◦C to 60 ◦C. Also, the conversion
of nitrobenzene has the same trend. The main reason is the
combined effect of the reaction temperature and the acidity of
the system in this case. Some more results and discussion on
this aspect are in the following content. A larger excess of Zn
in the system resulted in an increase of the fraction of aniline
Recently, the CO2/H2O system has been regarded as an
environmentally benign alternative to conventional acids. When
water is pressurized by CO2, pH values of the system can be as
low as 3.1,11 and the system will be self-neutralized on the release
of CO2. Several research works have been reported involving
aCollege of Chemical Engineering, State Key Laboratory of Fine
Chemicals, Dalian University of Technology, Dalian, 116012, China
bCollege of Chemistry, Jilin Normal University, Siping, 136000, China
† Electronic supplementary information (ESI) available: Characterisa-
tion data for the products. See DOI: 10.1039/b906283a
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Table 1 The effects of different reaction conditions on the selective reduction of nitrobenzenea
Entry
Zn/mmol
PCO /MPa
T/◦C
t/h
Conv.b (NB)/%
Yieldb (PHA)/%
Yieldb (AN)/%
2
1
2
3
4
5
6
7
8
9
10
11
12
13
30
30
30
30
30
30
30
30
22
40
50
30
30
0
40
40
40
40
40
40
20
60
40
40
40
40
40
3
3
3
3
3
3
3
3
3
3
3
2
4
3
57
100
98
100
99
87
68
80
100
100
89
trace
42
76
62
52
14
68
49
60
45
0
0
6
14
28
39
77
7
15
11
48
100
10
65
0.1
0.5
1
1.5
5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
70
26
100
a Reaction condition: NB 10 mmol, H2O 20 mL. b Determined by HPLC, small amount of azoxybenzene was also detected.
in the products (entries 3, 9–11). Under the reaction condition
applied, nitrobenzene was reduced to aniline completely if the
molar ratio of Zn to nitrobenzene was equal to 5 (entry 11).
When the reaction time was prolonged (entries 3, 12, 13), the
fraction of aniline in the products increased, too.
The above-mentioned results show that the introduction of
CO2 to the reaction system is essential to promote the reduction
of nitrobenzene to N-phenylhydroxylamine. A very important
matter is that the reaction can take place even at normal
CO2 pressure. Although the reaction result is not the best, the
possibility to run the reaction under normal CO2 pressure is very
convenient. So a systematic study on the reaction parameters to
optimize the yield of N-phenylhydroxylamine is carried out, and
the reaction is run in a 100 mL three-necked glass bottle with
CO2 bubbling through the water phase for a better adsorption.
Fig. 1 shows the results of the influence of reaction tempera-
ture on the reaction.
condition (see Table 1). When the reaction temperature is higher
than 60 ◦C, the conversion of nitrobenzene is increased gradually
with the increase of the reaction temperature. It seems that the
reaction is affected to a greater extent by the acidity of the system
in the temperature range from 0 ◦C to 60 ◦C. That is, the reaction
is accelerated by both the increase of the acidity of the reaction
system and the increase of reaction temperature. But the acidity
of the system is decreased as the CO2 solubility decreases with
the increase of the◦reaction temperature. When the temperature
is higher than 60 C, the negative effect of the decrease of the
acidity of the system on the reaction becomes not so serious.
Over the range of the reaction temperature investigated, the
reaction selectivity to N-phenylhydroxylamine in the reaction
products does not change much.
The results of different amount of Zn dust on the reduction
are illustrated in Fig. 2. With an increase of the molar ratio of
Zn to nitrobenzene, the conversion of nitrobenzene increased.
The yield of N-phenylhydroxylamine reached the maximum
when the ratio of Zn to nitrobenzene was equal to 3 under the
reaction conditions adopted. Further increase of the ratio of Zn
to nitrobenzene leads to an increase of the amount of aniline,
the complete reduction product.
Fig. 1 The effect of temperature on the reaction.
It is interesting◦to see from Fig. 1 that in the temperature range
◦
from 0 C to 60 C, the conversion of nitrobenzene as well as
the yield of N-phenylhydroxylamine reached to a maximum at
25 ◦C, and decreased again to a minimum at 55 ◦C. These results
are similar to the results obtained in the pressurized reaction
Fig. 2 The effect of molar ratio of Zn to NB on the reaction.
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Table 2 The reduction of various substituted nitrobenzenes using Zn in CO2/H2O systema
Run
1
Substrate
Product
Substrate conv.b/%
99
Product Yieldb/%
95
94
88
99
2
3
4
100
98
99
5
99
90
a Reaction conditions: substrate 5 mmol, Zn 15 mmol, H2O 20 mL, PCO 0.1 MPa, 25 ◦C, 1.0 h. b Calculated by 1H NMR data.
2
The reaction results with different reaction times are shown in
Fig. 3. It could be seen that the yield of N-phenylhydroxylamine
reached up to 88% when the reaction time was 1.5 hours.
Further increase of the reaction time results in increasing the
content of aniline in the reaction products. So to monitor the
reaction product during the reaction progress is very important
to optimize the yield of N-phenylhydroxylamine.
out at 25 ◦C for 1.5 hours with a Zn to nitrobenzene molar
ratio equal to 3 under 0.1 MPa CO2. Nitroarenes having other
reducible functional groups can also be selectively transformed
to the corresponding N-arylhydroxylamines. The method pro-
vides an environmentally benign way for the preparation of
N-arylhydroxylamines.
Experimental
Materials and reaction procedure
Nitroarenes and Zn dust are commercial products and used
without further purification. An appropriate amount of ni-
troarene, Zn dust and water were placed in a reactor. The reactor
was put in a preheated oil bath with magnetic stirring and
then CO2 was charged to the reactor for a fixed time. After
completing the reaction, the suspension was filtered, the solid
was washed with CH2Cl2, and the filtrate was extracted by
CH2Cl2. The combined organic phase was dried over anhydrous
MgSO4. The crude product was obtained from the organic
phase by evaporation and the product analysis was performed
by HPLC or by 1H NMR. The solid was further purified
by recrystallisation from the solvent mixture of CH2Cl2 and
petroleum ether (bp 60–90 ◦C).
Product analysis and characterization. Melting points of the
Fig. 3 The effect of reaction time on the reaction.
products were measured on a X-6 (Beijing Tech. instrument Co.
1
Ltd) melting-point apparatus. H NMR spectra were recorded
This new method is also applicable for the selective reduction
of nitrobenzenes substituted with other reducible functional
groups, such as –COCH3 and –CN. The scope and generality of
this method is illustrated with several examples and the results
are summarized in Table 2.
on Inova 400 (Varian, USA). The data of melting points and 1H
NMR spectra of these N-arylhydroxylamines were consistent
with those reported in the literature. The analyses of the products
from the reduction of nitrobenzene were performed by HPLC on
Agilent 1100 series (column: Agilent TC-C18, 4.6 mm ¥ 250 mm,
5 mm; UV detector: 254 nm; eluent: water–methanol).
Conclusion
In conclusion, the selective reduction of nitroarenes to
N-arylhydroxylamines is realized using Zn dust in a CO2/H2O
system. Nitrobenzene can be reduced to N-phenylhydroxyl-
amine with a yield of 88% when the reaction was carried
Acknowledgements
This work was supported by the Doctoral Fund of Ministry of
Education of China (Grant No: 20070141046).
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