Multiphase oxidation of aniline to nitrosobenzene with hydrogen peroxide catalyzed by heteropolyacids

Article abstract of DOI:10.1055/s-2008-1072502

Keggin-type heteropolyacids have been used as catalyst for high-yielding oxidation reactions in multiphase conditions. This simple and efficient procedure promoted the conversion of anilines to the corresponding nitroso and nitro derivatives. In comparison with homogeneous system the oxidation from anilines to nitroso compounds and nitro compounds were more effective and the solvents used were not toxic. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1072502

LETTER
967
Multiphase Oxidation of Aniline to Nitrosobenzene with Hydrogen Peroxide
Catalyzed by Heteropolyacids
do,*a,b G. P. Romanelli, P. G. Vázquez, A. Loris, F. Aricò
c
c
a
a
M
P
ultiphase
O
x
.
idation of
A
T
niline to Nitros
u
obenzene
w
i
n
O
2
2
a
Interuniversity Consortium ‘Chemistry for the Environment’, Via della Libertà 5/12, 30175 Marghera Venice, Italy
Department of Environmental Science, Cà Foscari University, Dorsoduro 2137, 30123 Venice, Italy
E-mail: tundop@unive.it
Centro de Investigación y Desarrollo en Ciencias Aplicadas ‘Dr. Jorge Ronco’ (CINDECA), Universidad Nacional de La Plata,
CONICET, Calle 47 N 257 (B1900AJK) La Plata, Argentina
b
c
Received 13 December 2007
type HPAs for the oxidation reaction of phenols and sul-
fur, predominately under homogeneous conditions.1
Abstract: Keggin-type heteropolyacids have been used as catalyst
for high-yielding oxidation reactions in multiphase conditions. This
5,16
simple and efficient procedure promoted the conversion of anilines Recently, we discovered a more convenient procedure for
to the corresponding nitroso and nitro derivatives. In comparison
the oxidation of organic compounds using aqueous hydro-
with homogeneous system the oxidation from anilines to nitroso
gen peroxide promoted by HPAs in a triphasic system;
compounds and nitro compounds were more effective and the sol-
comprising an aqueous solution of hydrogen peroxide, an
vents used were not toxic.
organic solvent and an ionic liquid. Addition of Aliquat
Key words: multiphase system, Keggin polyoxometalate, hydro-
gen peroxide, oxidation, aniline
3
36 to such a system, leads to formation of a third phase
which resides between the aqueous phase and the organic
phase. The oxidation reaction takes place in this third
phase with the presence of HPA. Under these conditions,
the observed selectivity is higher and the loss of hydrogen
Nitroso compounds are very useful in organic chemistry
as they undergo a variety of transformations such as ni-
17
peroxide is dramatically reduced. Such behavior renders
1
2
troso aldol reactions, nitroso ene reactions, [2+2] and
the system suitable for a continuous process as the reac-
tion components can be easily separated; the products re-
side in the organic phase, the oxidant in the aqueous phase
and the catalyst within the Aliquat 336 phase.
3
4
[
2+3] cycloadditions, addition of Grignard reagents, and
5
formation of azobenzenes. Additionally, these com-
pounds have been examined for their potential use as an-
tiretroviral and antitumor agents.
6
In this paper we describe the selective oxidation of aniline
to nitrosobenzene employing isooctane, aqueous hydro-
gen peroxide (35% p/V) and Aliquat 336 as an ionic liquid
Nevertheless, a simple high-yielding procedure for the
preparation of nitrosobenzenes remains unreported. Sev-
eral oxidation methods for preparation of nitrosoarenes
from anilines have been recently published, employing
various oxidizing agents such as peracetic acid, 3-chlo-
roperoxybenzoic acid, oxone and potassium permangan-
(
Scheme 1). Several HPAs were examined as catalysts at
ambient temperature, while additional control experi-
ments were conducted using homogeneous conditions
(
acetonitrile), biphasic conditions (isooctane and H O)
2
7
ate.
and a triphasic system in the absence of a HPA. Addition-
Alternatively, the use of aqueous hydrogen peroxide as an ally, the effect on selectivity by variation of the reaction
oxidant is very attractive and has previously been em- temperature was investigated.
ployed for the oxidation of anilines to nitroso compounds
8
9
10
in the presence of rhenium, tungsten and molybdenum
catalysts, giving high yields of nitroso derivatives.
NH2
NO
NO2
H2O2/HP As
Aliquat 336
2 2
H O /HP As
Aliquat 336
The demand for environmentally friendly processes has
prompted researchers to investigate the use of heteropoly-
acids (HPAs) as catalysts, since they represent a green
class of oxidation catalysts when they are used in the pres-
ence of aqueous hydrogen peroxide as an oxidizing
isooctane, 20 °C
isooctane, 60 °C
Scheme 1 Oxidation of aniline in multiphasic system
The Keggin structure for all of the prepared catalysts18
was verified by FT-IR; the spectral data were in agree-
1
1
agent.
In the literature, several examples for the use of HPAs as ment with those of the catalysts that we previously pre-
1
2–14
oxidation catalysts have been described.
In the past pared and characterized by NMR, DRX, thermal analysis,
few years, our research group has been studying the syn- TPR and voltamperometry.
thesis, characterization and application of new Keggin-
The acidic properties of heteropolyacids were measured
by potentiometric titration with n-butylamine.
SYNLETT 2008, No. 7, pp 0967–0970
Advanced online publication: 17.03.2008
DOI: 10.1055/s-2008-1072502; Art ID: D39807ST
x
x.
x
x.
2
0
0
8
A preliminary series of reactions was conducted using the
heteropolyacid catalyst H
PMo12O40 (M12P) and hydro-
3
©
Georg Thieme Verlag Stuttgart · New York
gen peroxide as the oxidizing agent. Oxidation of aniline

9
68
P. Tundo et al.
LETTER
2
0
to nitrosoaniline at ambient temperature was examined in nadium present in the structure. Even more remarkable
various reaction systems. These were: (a) a homogeneous was the effect on conversion by incorporation of alumi-
system using acetonitrile as solvent, (b) a biphasic system num into the primary structure of the HPA; inclusion of
using isooctane and water, (c) a multiphasic system with one atom of aluminum increased the extent of conversion
isooctane, water and Aliquat 336 in the absence of catalyst from 36 to 74%. However, the most active catalyst under
and, (d) a multiphasic system as described in (c) with the the examined conditions contained both aluminum and
presence of H PMo O as catalyst. The extent of conver- vanadium within the heteropolyanion; the catalyst
3
12 40
sion for the aforementioned reaction systems is depicted M PAl0.5V0.5 gave 90% conversion with 100% selectivity
11
1
9
in Figure 1.
towards nitrosobenzene formation.
Table 1 Selective Oxidation of Aniline to Nitrosobenzene at 20 °C
(7 h), Employing Different HPAs as Catalysts in the Multiphasic Sys-
tem
Entry
Catalyst
Conv.
PhNO
(%)
PhNO2
(%)
(
%)
71
98
1
2
3
4
5
6
7
8
9
H PMo O
96
97
93
94
95
90
87
82
91
4
3
3
12 40
H PBMo O
6
11 40
H PAlMo O
100
98
7
6
11 40
H PVMo O
6
4
11 40
H PAl 0.5V 0.5Mo O
98
5
6
11 40
H PV2Mo O
100
100
100
100
10
13
18
9
7
10 40
Figure 1 Selective oxidation of aniline to nitrosobenzene at 20 °C
employing M12P as catalyst. The curves show the influence of the re-
action media on conversion: (a) a homogeneous system, (b) a biphasic
system, (c) a multiphasic system without catalyst and (d) a multipha-
sic system including catalyst
H
PV Mo O
6 6 40
9
H PV Mo O
40
11
8
4
H PBiMo O
5
11 40
The reactions were carried out at 20 °C for seven hours.
The catalyst M12P was employed in a 2-mmol% amount
and hydrogen peroxide was used in a 35%-p/V solution.
Further experiments were carried out to examine the influ-
ence of iron, by substitution of hydrogen within the HPA
structure. The multiphasic reaction system (d) was em-
ployed with the following HPAs: the iron–containing cat-
alysts M11.5PV Fe and M PVFe, and for comparison,
With the exception of the reaction conducted in acetoni-
trile [system (a)], the selectivity ranged from 90–100%
using conditions (b)–(d), with nitrobenzene being the only
observable by-product. No conversion was observed in
the homogeneous acetonitrile system (a). In the biphasic
system (b) the extent of conversion was 38% and the se-
lectivity for nitrosobenzene was 90%, with the remaining
0.5
11
M11.5PV0.5 and M11PV. The results are reported in
Figure 2.
1
0% attributed to nitrobenzene. In the multiphasic system
(
c) which comprised isooctane, Aliquat 336 and water in
the absence of catalyst, the extent of conversion was
found to be 6% with no detectable by-products. In the
same triphasic system with the inclusion of catalyst M12P
[
system (d)] the extent of conversion was 76% with a se-
lectivity of 96%.
A series of experiments, performed in the multiphasic sys-
tem (d), was then conducted in order to examine the per-
formance of different heteropolyacids towards selective
oxidation of aniline to nitrosobenzene. The HPA catalysts
that were used, H PV Mo O , H PVMo O ,
3
.5
0.5
11.5 40
4
11 40
H PV Mo O , H PAlMo O and H PA V Mo O
9
6
6
40
6
11 40
5
l0.5 0.5
11 40
Figure 2 Selective oxidation of aniline to nitrosobenzene at 20 °C
after 7 h. The curves show the influence of iron within the structure
of the catalyst on extent of conversion.
differed from M12P by inclusion of vanadium and/or alu-
minum. As shown in Table 1, inclusion of vanadium into
the structure of the HPA improved the activity of the cat-
alyst, which was attributed to an increase in the reduction
potential which directly correlates with the amount of va-
As illustrated in Figure 2, substitution of hydrogen with
iron enhanced the activity of the catalyst, which resulted
Synlett 2008, No. 7, 967–970 © Thieme Stuttgart · New York

LETTER
Multiphase Oxidation of Aniline to Nitrosobenzene with H O2
969
2
in 76% conversion to nitrosobenzene in 60 minutes by use Table 2 Synthesis of Nitroso Derivatives in a Multiphase System at
2
0 °C Using as Catalyst HFePMo VO (Reaction Time: 7 h)
11 40
of M PVFe. In contrast, a lower conversion of 36% was
1
1
obtained with the use of M11PV after 60 minutes. Despite
the differences in extent of conversion, 100% selectivity
for nitrosobenzene was observed in both cases. Further-
more, the iron-substituted catalysts promoted higher con-
versions within shorter time frames also compared with
the catalysts shown in Table 1. Such improved activity
cannot be ascribed to the variation of reduction potentials,
since the presence of iron does not affect this value; it is
more likely to be due to the increased acidity of the cata-
lysts, since potentiometric titrations of iron-substituted
catalysts indicated higher electrode ionization potentials.
Entry Substrate
Conv. (%) PhNO (%) PhNO (%)
2
1
2
3
4
5
aniline
100
99
91
99
92
92
85
9
1
4-methylaniline
2-methylaniline
4-chloroaniline
4-methoxyaniline
100
98
8
8
100
15
Table 3 Synthesis of Nitro Derivatives in a Multiphase System at
6
0 °C Using as Catalyst HFePMo VO (Reaction Time: 7 h)
11 40
The results of the previous experiments conducted in the
multiphase reaction system indicated that the iron-con-
taining catalyst, M PVFe, was the most active catalyst.
Entry Substrate
Conv. (%) PhNO (%) PhNO (%)
2
1
1
1
2
3
4
5
aniline
100
100
100
100
100
–
–
1
1
1
100
100
99
Therefore, this catalyst was examined in further experi-
ments at two different temperatures to establish the effect
on selectivity. The reactions were carried out at 20 and 60
4-methylaniline
2-methylaniline
4-chloroaniline
4-methoxyaniline
°
C. As shown in Figure 3, the reaction conducted at 20 °C
showed 100% selectivity for nitrosobenzene with 76%
conversion after 60 minutes. In contrast, the reaction con-
ducted at 60 °C showed 100% selectivity for nitrobenzene
with 100% conversion after seven hours.
99
100
tween the oxidating aqueous phase and the organic phase
of the substrate. In fact both catalyst’s activity and selec-
tivities improved in the presence of a third phase.
Several catalysts containing aluminum and vanadium in
the primary structure of the heteropolyacid were studied.
Moreover the effect of the substitution of hydrogen with
iron atoms was reported. All substituted catalysts showed
better activity than the commercial (M12P) one. The im-
proved activity of the vanadium-containing HPAs is relat-
ed to the corresponding increased redox potentials. On the
other hand, the explanation for the increased activity of
aluminum and/or iron-containing structures is more com-
plicated and appears to be related to the increased acidity
Figure 3 Oxidation of aniline in the multiphasic system using of catalysts.
M PVFe as catalyst. The curves show the influence of temperature
on product selectivity.
1
1
The M PVFe catalyst was employed to study the selec-
11
tivity at two different temperatures. Keeping all the pa-
rameters same, the reactions were carried out at 20 and 60
Once the reaction conditions for the selective oxidation of
aniline to nitroso and nitro derivatives had been opti-
mized, the reaction was extended to other substrates.
Table 2 shows the results for the selective oxidation of
different anilines to nitroso compounds. In all cases the
conversion to the related nitroso compound was complet-
ed in a short reaction time and the products were obtained
in excellent yields (85–99%) and high selectivity. Table 3
reports the results for the selective oxidation of different
anilines to nitro compounds. The reaction was performed
at 60 °C and also in this case, yields were very high (99–
°C; in the former case selectivity was 100% towards ni-
trosobenzene, while in the latter case it was 100% towards
nitrobenzene, proving that selectivity is easily tunable by
changing the reaction temperature. Moreover, in the mul-
tiphase conditions, no appreciable decomposition of hy-
drogen peroxide was recorded.
One of the advantages of this methodology is that H O as
2
2
oxidant, as opposed to peracetic acid, 3-chloroperoxyben-
7
zoic acid, oxone and potassium permanganate, does not
produce any inorganic salts during the oxidation. Besides,
compared to other systems employing H O as oxidant, in
1
00%) and the reaction was extremely selective.
2
2
the multiphase system the catalyst is confined in one of
the three phases, so allowing its recovery and reuse.
Therefore a continuous flow condition can be easily ap-
plied to this procedure.
In this work it was demonstrated that the multiphasic sys-
tem gives better results in the oxidation of aniline to ni-
trosobenzene using hydrogen peroxide as oxidant in the
presence of Keggin-type HPAs as catalysts. This method
represents a solution to the problem of incompatibility be-
Synlett 2008, No. 7, 967–970 © Thieme Stuttgart · New York

9
70
P. Tundo et al.
LETTER
Acknowledgment
(18) The commercial catalyst, H PMo12O40 (M12P), was
3
obtained from Aldrich. All the others were prepared
according to conventional procedures described in ref. 16.
Catalysts were characterized with a Bruker IFS 66 FT-IR
equipment, employing KBr discs. The acidity was measured
via potentiometric titration, adding little amounts of a
solution of n-butylamine in MeCN (0.05 N) to the suspended
solid (0.05 g) in MeCN (90 mL) stirred during the whole
procedure. The difference of potential (mV) was recorded
with a digital pHmeter (Instrumentalia S.R.L.), equipped
with a combined electrode.
The authors thank the Consorzio Interuniversitario Nazionale La
Chimica per lAmbiente (INCA), the Consejo Nacional de Investig-
aciones Científicas y Técnicas (CONICET) and the University of
La Plata.
References and Notes
(1) Oppolzer, W.; Tamura, O.; Sundarabau, G.; Signer, M.
J. Am. Chem. Soc. 1992, 114, 5900.
(
19) General Procedure for Oxidation in Homogeneous
Conditions: Reactions were carried out in a 25-mL 3-
necked round-bottomed flask, equipped with a refrigerator
and thermostated at working temperature. In the reactor were
charged aniline (1 mmol), a solution of n-decane in MeCN
as internal standard (0.56 mL), MeCN to reach an overall
(
(
2) Adam, W.; Krebs, O. Chem. Rev. 2003, 103, 4131.
3) Viehe, H. G.; Merenly, R.; Francotte, E.; Van Meersche, M.;
Germani, G.; Declerq, J. P.; Bodart-Gilmont, J. J. Am. Chem.
Soc. 1977, 99, 2340.
(4) Kopp, F.; Sapountzis, I.; Knochel, P. Synlett 2003, 885.
(5) Goelitz, P.; de Meijere, A. Angew. Chem. 1977, 16, 854.
(6) Rice, W. G.; Schaeffer, C. A.; Graham, L.; Bu, M.;
McDougal, J. S.; Orloff, S. L.; Villinger, F.; Young, M.;
Oroszlan, S.; Fesen, M. R.; Pommier, Y.; Mendeleyev, J.;
Kun, E. Nature (London) 1993, 361, 473.
volume of 5 mL, a solution of H O (35% p/V, 5 mL) and
2
2
heteropolyacid (2 mmol%). The reaction mixture was stirred
with a magnetic bar at 700 rpm.
General Procedure for Oxidation in Multiphasic
Conditions: The aforementioned procedure was employed
for reactions in multiphasic conditions, with the addition of
Aliquat 336 (2.32 mL) in isooctane (10% p/V) solution and
employing isooctane instead of MeCN as organic solvent.
Samples Analysis: Samples were withdrawn from the
organic phase at 20 min time intervals during a total reaction
period of 420 min. Each sample volume was approximately
(7) (a) Gowenlock, B. G.; Richter-Addo, G. B. Chem. Rev.
2
004, 104, 3315. (b) Yu, B.-C.; Shirai, Y.; Tour, J. M.
Tetrahedron 2006, 62, 10303. (c) Priewisch, B.; Ruck-
Braun, K. J. Org. Chem. 2005, 70, 2350.
(
(
8) Zhu, Z.; Espenson, J. H. J. Org. Chem. 1995, 60, 1326.
9) Giera, H.; Lange, W.; Meiers, M.; Pires, R. Eur. Patent
Appl., EP1099683A1, 2001.
20 mL and it was diluted with 1–2 mL of isooctane or MeCN.
(
10) (a) Tollari, S.; Cuscela, M.; Porta, F. J. Chem. Soc., Chem.
Commun. 1993, 1510. (b) Defoin, A. Synthesis 2004, 706.
11) Alizadeha, M. H.; Tayebee, R. J. Braz. Chem. Soc. 2005, 16,
The solution was stirred in the presence of silica gel and
filtered to remove the Aliquat 336 before the injection in the
GC. Concentrations were calculated with the internal
standard method. Conversions were obtained with GC
analysis performed with a Varian GC 3400 instrument, in the
presence of n-decane as internal standard. The capillary
column was a 30 m Chromopack CP Sil 8 CB, whose
diameter was 0.32 mm. The identification of products was
performed with GC–MS (detector HP 5971) for comparison
with authentic samples.
(
108.
(
(
(
12) Okujara, T.; Mizuno, M. Appl. Catal. A: Gen. 2001, 222, 63.
13) Corma, A. Chem. Rev. 1995, 95, 559.
14) (a) Risono, M. Chem. Commun. 2001, 1141. (b) Simonova,
M. V.; Zhizhina, E. G.; Russkikh, V. V.; Matveev, K. I.
Russ. Chem. Bull. 2005, 54, 1532.
(
(
(
15) Villabrille, P. I.; Romanelli, G. P.; Vàzquez, P. G.; Càceres,
C. V. Appl. Catal. A: Gen. 2004, 270, 101.
16) Romanelli, G. P.; Vàzquez, P. G.; Tundo, P. Synlett 2005,
(
20) Villabrille, P. I. PhD Thesis; Universidad Nacional de La
Plata: Argentina, 2006.
75.
17) Results not yet published.
Synlett 2008, No. 7, 967–970 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.