Selective reduction of nitroarenes to N-arylhydroxylamines by use of Zn in a CO2-H2O system, promoted by ultrasound

Article abstract of DOI:10.1007/s11164-012-0562-5

The promoting effect of ultrasound on the selective reduction of nitroarenes to N-arylhydroxylamines by use of Zn in an environmentally benign CO₂-H₂O system has been demonstrated. The yield of N-phenylhydroxylamine reaches 95% when the reaction is carried out with a Zn-to-nitrobenzene molar ratio of 2.2 under ultrasound (40 kHz) at 25 °C and normal pressure of CO₂ for 60 min. Application of ultrasound to the reaction has the advantages of higher yield of N-arylhydroxylamines, shorter reaction time, and consumption of less Zn. Springer Science+Business Media B.V. 2012.

Full text of DOI:10.1007/s11164-012-0562-5

Res Chem Intermed (2012) 38:2471–2478
DOI 10.1007/s11164-012-0562-5
Selective reduction of nitroarenes
to N-arylhydroxylamines by use of Zn in a CO2–H2O
system, promoted by ultrasound
•
•
•
Shijuan Liu Yanhua Wang Xun Yang
Jingyang Jiang
Received: 18 March 2012 / Accepted: 17 April 2012 / Published online: 24 May 2012
Ó Springer Science+Business Media B.V. 2012
Abstract The promoting effect of ultrasound on the selective reduction of
nitroarenes to N-arylhydroxylamines by use of Zn in an environmentally benign
CO2–H2O system has been demonstrated. The yield of N-phenylhydroxylamine
reaches 95 % when the reaction is carried out with a Zn-to-nitrobenzene molar ratio
of 2.2 under ultrasound (40 kHz) at 25 °C and normal pressure of CO2 for 60 min.
Application of ultrasound to the reaction has the advantages of higher yield of
N-arylhydroxylamines, shorter reaction time, and consumption of less Zn.
Keywords Nitroarenes ꢀ Reduction ꢀ Zn ꢀ CO2–H2O ꢀ Ultrasound ꢀ
N-Arylhydroxylamines
Introduction
N-Arylhydroxylamines, useful intermediates in the synthesis of fine chemicals [1–3]
and pharmaceuticals [4–6], are usually prepared by the selective reduction of the
corresponding nitroarenes. Methods for preparation of N-arylhydroxylamines
include catalytic hydrogenation [7–9], catalytic transfer hydrogenation [10, 11],
metal-mediated reduction [12], and others [13–16]. Zn-mediated reduction of
nitroarenes, a widely used conventional method, is performed in aqueous NH4Cl
solution. The method has the advantages of mild reaction conditions and good
product selectivity, but a large amount of NH4Cl is consumed and much waste is
produced.
S. Liu
College of Chemistry, Jilin Normal University, Siping 136000, China
S. Liu ꢀ Y. Wang ꢀ X. Yang ꢀ J. Jiang (&)
State Key Laboratory of Fine Chemicals, Faculty of Chemical Environmental and Biological
Science and Technology, Dalian University of Technology, Dalian 116012, China
e-mail: jyjiang@dlut.edu.cn
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S. Liu et al.
The accelerating effect of ultrasound on chemical reactions was first reported in
1927 [17]; since then ultrasound has been extensively applied in organic reactions.
Recently Ferround’s group [18] reported the promoting effect of ultrasound on Zn
mediated reduction of nitroarenes using NH4Cl. The reaction was complete in
5 min, and yields of the corresponding N-arylhydroxylamines were 75–95 %.
Later Shi [19] described the preparation of N-arylhydroxylamines by use of Zn–
HCOONH4-MeCN-ultrasound; selectivity for N-arylhydroxylamines was 90–98 %,
but their procedure still consumed ammonium salt and they did not report any
results on selective reduction of nitrobenzene.
Very recently, we developed a novel procedure using Zn in CO2–H2O for
selective reduction of nitroarenes to N-arylhydroxylamines [20, 21]. This environ-
mentally benign system is fully free from NH4Cl and the yield of N-phenylhydr-
oxylamine reaches 88 % under the optimum conditions. Nitroarenes with reducible
functionality in addition to nitro groups were also reduced selectively to the
corresponding N-arylhydroxylamines. In this manuscript we report the promoting
effect of ultrasound (40 kHz) on the selective reduction of nitroarenes to
N-arylhydroxylamines using Zn in CO2–H2O.
Experimental
Apparatus and analysis
Nitroarenes and Zn dust were commercial reagents and were used without further
purification. Ultrasound was produced by a KQ5200B ultrasonic cleaner (200 W,
40 kHz; Kunshanshi Chaosheng Instrument, China). Melting points of the products
1
were measured on a X-6 (Beijing Tech. Instrument) melting-point apparatus. H
NMR spectra were recorded on Inova 400 (Varian, USA) and chemical shifts were
1
recorded in ppm from TMS as internal standard. Melting points and H NMR
spectra of the N-arylhydroxylamines obtained were consistent with those reported in
the literature [22–26]. Analysis of products from reduction of nitrobenzene was
performed by HPLC on an Agilent 1100 series (column: Agilent TC-C18,
4.6 mm 9 250 mm, 5 lm; UV detection: 254 nm; mobile phase: water–methanol).
Typical procedure for preparation of N-arylhydroxylamines
Appropriate amounts of nitroarene, Zn dust, and water were placed in a 100-mL
three-necked flask which was equipped with mechanic stirrer and condenser. The
flask was immersed in the water bath of the ultrasonic cleaner, then CO2 was
bubbled through the reaction mixture which was sonicated under mechanical
stirring at the designed temperature for a fixed time. After completion of the
reaction, the suspension was isolated by filtration, the solid was washed with
CH2Cl2, and the filtrate was extracted with CH2Cl2. The combined organic phase
was dried over anhydrous MgSO4. The crude product was obtained from the organic
phase by evaporation and product analysis was performed by HPLC or by 1H NMR.
123

The selective reduction of nitroarenes to N-arylhydroxylamines
2473
The product was purified by recrystallization from a mixture of CH2Cl2 and
petroleum ether (bp 60–90 °C).
Characterization data for the products
1
N-(4-acetophenyl) hydroxylamine mp 116–117 °C. H NMR (400 MHz, DMSO-
d6): dH 2.45 (s, 3 H, CH3), 6.83 (pseudo-q, 2 H, JAX ?JAX = 8.4 Hz, A–H and A0–
0
H), 7.80 (pseudo-q, 2 H, JAX ?JAX = 8.4 Hz, X–H and X0–H), 8.69 (s, 1 H, OH),
9.01 (s, 1 H, NH).
0
1
N-(4-cyanophenyl) hydroxylamine mp 85–86 °C. H NMR (400 MHz, DMSO-
d6): dH 6.86 (pseudo-q, 2 H, JAX ?JAX = 8.8 Hz, A–H and A0–H), 7.55 (pseudo-q,
0
2 H, JAX ?JAX = 8.8 Hz, X–H and X0–H), 8.76 (s, 1 H, OH), 9.10 (s, 1 H, NH).
0
N-(3-nitrophenyl) hydroxylamine mp 118 - 119 °C. 1H NMR (400 MHz, DMSO-
d6): dH 7.20 (br d, 1 H, J = 8.0 Hz, 6-H), 7.44 (t, 1 H, J = 8.0 Hz, 5-H), 7.59 (br d,
1 H, J = 8.0 Hz, 4-H), 7.63 (br s, 1 H, 2-H), 8.76 (s, 1 H, OH), 8.88 (s, 1 H, NH).
1
N-(p-tolyl) hydroxylamine mp 82–84 °C. H NMR (400 MHz, CDCl3): dH 2.29
(s, 3 H, CH3), 6.47 (br s, 2 H, NH and OH), 6.90 (pseudo-q, 2 H, JAX
?JAX = 8.0 Hz, A–H and A0–H), 7.08 (pseudo-q, 2 H, JAX ?JAX = 8.0 Hz, X–H
0
0
and X0–H).
1
N-(4-bromophenyl) hydroxylamine mp 92–93 °C. H NMR (400 MHz, CDCl3):
0
dH 5.79 (br s, 2 H, NH and OH), 6.87 (pseudo-q, 2 H, JAX ?JAX = 8.0 Hz, A–H and
A0–H), 7.37 (pseudo-q, 2 H, JAX ?JAX = 8.0 Hz, X–H and X0–H).
0
1
N-(2-chlorophenyl) hydroxylamine mp 53–54 °C. H NMR (400 MHz, DMSO-
d6): dH 6.77 (t, 1 H, J = 7.6 Hz, ArH), 7.17–7.25 (m, 3 H, ArH), 8.19 (s, 1 H, OH),
8.56 (s, 1 H, NH).
1
N-(3-chlorophenyl) hydroxylamine mp 49–50 °C. H NMR (400 MHz, DMSO-
d6): dH 6.75 (br d, 2 H, J = 8.0 Hz, 4-H and 6-H), 6.84 (br s, 1 H, 2-H), 7.16 (t, 1 H,
J = 8.0 Hz, 5-H), 8.51 (s, 1 H, OH), 8.53 (s, 1 H, NH).
1
N-(4-chlorophenyl) hydroxylamine mp 83–84 °C. H NMR (400 MHz, CDCl3):
0
dH 6.09 (br s, 2 H, NH and OH), 6.99 (pseudo-q, 2 H, JAX ?JAX = 8.8 Hz, A–H and
A0–H), 7.30 (pseudo-q, 2 H, JAX ?JAX = 8.8 Hz, X–H and X0–H).
0
Results and discussion
Selective reduction of nitrobenzene (NB) to N-phenylhydroxylamine (PHA) was
examined under different conditions; the results were listed in Table 1. From
Table 1 it is apparent that the reaction did not occur without bubbling CO2, even
though both mechanical stirring and ultrasound were applied (entries 1 and 2). In
contrast, 5 % conversion of nitrobenzene was achieved if CO2 was bubbled into the
reaction mixture with no other treatment (entry 3). With the combination of CO2
bubbling and mechanical stirring, conversion of nitrobenzene and yield of N-
phenylhydroxylamine were 50 % and 47 % respectively (entry 5) for a reaction
time of 60 min, and the latter was only 76 % when the reaction period was four
times longer (entry 7). Higher yield of N-phenylhydroxylamine could be achieved at
the expense of use of an excessive amount of Zn (entries 8 and 9). The results given
123

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S. Liu et al.
Table 1 Selective reduction of nitrobenzene to N-phenylhydroxylamine under different conditionsa
Entry PCO
Stirring
U.b
Zn
(mmol)
t (min) NB Conv.c PHA Yieldc Selec.c to PHA
2
(MPa)
(%)
(%)
(%)
1
0
Without Yes 22
With Yes 22
Without No 22
Without Yes 22
60
60
60
60
60
60
240
90
60
30
60
30
60
0
0
0
0
0
0
2
0
3
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
5
4
80
87
94
95
89
89
93
94
11
89
92
4
8
7
5
With
With
With
With
With
With
With
With
With
No
22
50
98
86
99
98
98
99
57
90
47
93
76
88
91
92
11
51
83
6
Yes 22
7
No
No
No
22
30
40
8
9
10
11
12
13
a
Yes 30
Yes 30
No
No
30
30
Reaction conditions: NB 10 mmol, H2O 30 mL, 25 °C
Under ultrasound
b
c
Determined by HPLC
for entries 4–6 revealed that selective reduction of nitrobenzene with the
combination of CO2 bubbling, mechanical stirring, and ultrasound irradiation was
the best. 98 % conversion of nitrobenzene and 93 % yield of N-phenylhydr-
oxylamine were obtained (entry 6). It was found that when more Zn was used
(Zn:NB = 3), a good yield of N-phenylhydroxylamine (92 %) was obtained in
shorter time (30 min) (entry 10) and a further increase in the reaction time resulted
in reduced yield of N-phenylhydroxylamine because of its further reduction to
aniline (AN) (entry 11). However, without ultrasound the reaction was less efficient,
and the yield of N-phenylhydroxylamine was 51 % and 83 % for reaction time of 30
and 60 min, respectively (entries 12 and 13).
In summary, higher yield of N-phenylhydroxylamine was obtained with smaller
Zn-to-nitrobenzene molar ratio and shorter reaction time when ultrasound was
applied.
Selective reduction of nitrobenzene to N-phenylhydroxylamine using Zn in CO2–
H2O is more efficient under the action of ultrasound. This phenomenon may be
attributed to the cavitation effect caused by ultrasound in the solid–liquid
heterogeneous reaction medium. The formation of N-phenylhydroxylamine from
nitrobenzene involves the following steps:
1
2
3
transfer of nitrobenzene to the Zn0 surface from the solution;
adsorption of nitrobenzene on the Zn0 surface;
chemical reaction on the Zn0 surface, which involves formation of
N-phenylhydroxylamine and its successive reduction to aniline;
desorption of the products from the solid surface; and
transfer of the products into the solution.
4
5
123

The selective reduction of nitroarenes to N-arylhydroxylamines
2475
Fig. 1 The effect of reaction temperature on the reaction
So desorption of N-phenylhydroxylamine from the metal surface would preclude
the further reduction. Although mechanical stirring would enhance mass transfer
between the solution and the metal surface to some extent, its main effect is to make
the whole system turbulent, a long-range effect. On the metal surface there is a near
static thin liquid layer (short range) and mass transfer through this layer is less
affected by mechanical stirring. When ultrasound is applied in a solid–liquid
heterogeneous system, ultrasonic activation occurs, i.e. as a consequence of the
mechanical effects of cavitation a liquid jet propagates toward the solid–liquid
phase boundary with high velocity, and hits the solid surface violently [27]. As a
result, the metal surface may be continuously cleaned by the shock wave and
microjets formed during cavitation bubble collapse. Thus application of ultrasound
compensated for the deficiency of mechanical stirring. In addition, the Zn0 surface
would be increased, because of rupture of particles by the highspeed microjet when
the cavity implodes asymmetrically [28, 29]. Hence, higher reaction efficiency is
achieved under the action of ultrasound, and the selectivity and the yield of N-
phenylhydroxylamine are higher under these conditions.
To optimize the yield of N-phenylhydroxylamine, the effects of different reaction
conditions were studied.
The results of the reaction with and without ultrasound at different temperature
are shown in Fig. 1. From Fig. 1, it can be seen that conversion of nitrobenzene and
yield of N-phenylhydroxylamine in the reaction under the action of ultrasound were
higher than those in the reaction without ultrasound. In the temperature range from 0
to 50 °C, conversion of nitrobenzene and yield of N-phenylhydroxylamine reached
a maximum at 25 °C. The reason is that the reaction is accelerated by both
increasing acidity of the reaction system and an increase in the reaction temperature.
But the acidity of the reaction system is reduced as the solubility of CO2 in H2O
decreases with increasing reaction temperature.
123

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S. Liu et al.
In the range of reaction temperature examined, the yield of aniline, the by-
product from further reduction of N-phenylhydroxylamine, is low (less than 5 %).
The reaction results with different reaction time and different amounts of water
used in the system under the action of ultrasound are listed in Table 2.
It is apparent the optimum yield of N-phenylhydroxylamine (95 %) was obtained
under the reaction conditions used for the entry 7 in Table 2.
Table 2 Selective reduction of nitrobenzene to N-phenylhydroxylamine using Zn in CO2–H2O under
different reaction conditionsa
Entry
t (min)
H2O (mL)
NB Conv.b (%)
PHA Yieldb (%)
Selec.b to PHA (%)
1
2
3
4
5
6
7
8
a
30
40
50
60
80
60
60
60
30
30
30
30
30
20
40
50
73
88
92
98
98
89
98
95
70
84
87
93
91
82
95
92
96
95
95
95
93
92
97
97
Reaction conditions: NB 10 mmol, Zn 22 mmol, 25 °C, PCO2 0.1 MPa, ultrasound 40 kHz
Determined by HPLC
b
Table 3 Selective reduction of different nitroarenes by use of Zn in CO2–H2Oa
Entry
R
Zn (mmol) H2O (mL) t (min) a Conv.b (%) b Yieldb (%) Selec.b
to b (%)
1
p-COCH3 11
40
40
40
40
40
40
40
40
20
20
20
20
20
40
40
40
40
40
40
40
40
60
60
60
60
60
98
99
96
97
99
98
99
99
100
98
99
99
99
92
98
95
94
94
97
98
97
94
88
99
90
95
94
99
99
97
95
99
99
98
94
90
100
91
96
2
p-CN
m-NO2
p-CH3
p-Br
11
11
11
11
11
11
11
3
4
5
6
o-Cl
7
m-Cl
p-Cl
8
9c
10c
11c
12c
13c
p-COCH3 15
p-CN
m-NO2
p-CH3
p-Cl
15
15
15
15
Bold ‘‘a’’ represents nitroarene substrate, bold ‘‘b’’represents N-arylhydroxylamine product, which are
described in Scheme1 as ‘‘a’’ and ‘‘b’’ .
a
Reaction conditions: substrate 5 mmol, PCO 0.1 MPa, 25 °C, ultrasound 40 kHz
2
b
Calculated from 1H NMR data
c
These data were taken from Ref. [20]
123

The selective reduction of nitroarenes to N-arylhydroxylamines
Scheme 1 The selective
2477
Zn, H2O
NHOH
NO2
reduction of various nitroarenes
))))
R
CO2 0.1 MPa,
R
a
b
Nitroarenes with other functional groups, for example –Cl, –Br, –COCH3, and –
CN, were also tested in the reaction under the action of ultrasound (Scheme 1); the
corresponding yields of N-arylhydroxylamines were also high (92–98 %), as shown
in Table 3.
Compared with our previous results [20], high yields of N-arylhydroxylamines
were obtained with smaller Zn-to-nitrobenzene molar ratio (from 3 to 2.2) and
shorter reaction time (from 60 to 40 min). Ultrasound substantially enhanced the
efficiency of the reaction.
Conclusion
In summary, the promoting effect of ultrasound on the selective reduction of
nitroarenes to N-arylhydroxylamines using Zn in an environmentally benign CO2–
H2O system was demonstrated. Higher yield of N-arylhydroxylamines could be
obtained with less Zn consumption and shorter reaction times under the action of
ultrasound. Use of ultrasound makes the reaction more efficient.
Acknowledgments This work was supported by the Doctoral Fund of the Ministry of Education of
China (grant no: 20070141046).
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