Catalytic system for pyridine oxidation to N-oxides under mild conditions based on polyoxomolybdate

Article abstract of DOI:10.1039/c5ra05196g

A reusable and effective catalytic system has been developed for oxidation of pyridines catalyzed by Keplerate polyoxomolybdate ({Mo₁₃₂}) at room temperature. Pyridine compounds could be oxidized in high yields under mild conditions.

Full text of DOI:10.1039/c5ra05196g

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Catalytic system for pyridine oxidation to N-oxides
under mild conditions based on
polyoxomolybdate†
Cite this: RSC Adv., 2015, 5, 36809
Received 24th March 2015
Accepted 14th April 2015
Chunxia Yang, Wei Zhao,* Zhiguo Cheng, Baomin Luo and Dongqin Bi
DOI: 10.1039/c5ra05196g
www.rsc.org/advances
A reusable and effective catalytic system has been developed for effective catalyst with hydrogen peroxide have received much
7
oxidation of pyridines catalyzed by Keplerate polyoxomolybdate attention in recent years. Some reusable and mild catalytic
(
{Mo132}) at room temperature. Pyridine compounds could be oxidized systems for pyridine oxidation based on polyoxometalates with
8
in high yields under mild conditions.
hydrogen peroxide have been developed. In these systems,
several pyridines were oxidized to corresponding N-oxides with
high yields, and the catalyst could be reused aer rst reaction.
However, there were some disadvantages for the procedures,
such as long reaction time during oxidation of pyridine deriv-
atives and high reaction temperature during oxidation of
quinoline derivatives.
As a class of well-dened inorganic transition-metal oxide
clusters, polyoxometalates (POMs) have been studied for many
years. Due to their functional properties with abundant
compositions, POMs are commonly used in catalysis, medicine,
1
imaging, sensing, and multifunctional materials. Among them,
To expand applications of Keplerate polyoxomolybdate
catalysis is particularly one of important research eld based on
polyoxometalates. Because of green chemistry, hydrogen peroxide
as a mild oxidant was used widely in catalytic oxidations. POMs,
as effective catalysts for oxidation reaction with hydrogen
peroxide have drawn wide attention in the past years, such as
(
{Mo132}) in catalytic reactions and avoid the shortcomings in
previous catalytic systems for pyridine oxidation, herein we
develop an effective and reusable catalytic system for pyridine
oxidation to N-oxides catalyzed by {Mo132}. In this system,
heterocyclic N-oxides were obtained in high yields by oxidation
of pyridines in mixed solvent of water and ethanol at room
temperature catalyzed by {Mo132} with aqueous hydrogen
peroxide (see Scheme 1). Pyridine and its derivatives could be
oxidized in high yields during short time at room temperature.
Interestingly, quinoline and its derivatives also could be
oxidized in high yields at room temperature, which could not be
achieved in previous reported similar systems. In addition, the
catalyst aer reaction could be recovered and reused for several
times without obvious loss in activity.
Table 1 summarizes the results of catalytic oxidation of
different pyridine and its derivatives based on {Mo132} with
hydrogen peroxide in the mixed solvent (water and ethyl
alcohol). To obtain high yields of products, 5 equivalents of
hydrogen peroxide were used in the system. Pyridine was
successfully oxidized to pyridine N-oxide with 93% yield during
six hours at room temperature (Table 1, entry 2). The control
2
3
alcohol oxidation, sulfur compound oxidation and olen epox-
4
idation. In above catalytic systems, Keggin polyoxometalates
with saturated, lacunary or transition-metal-substituted struc-
tures were mostly used as effective catalysts. Other structures of
polyoxometalates have been reported less used for catalytic
reactions. Recently, giant polyoxomolybdate with Keplerate
VI
72
V
structure [(NH ) [Mo Mo60 O372(CH COO) (H O) ]({Mo132})
4
42
3
30
2
72
was reported as effective catalyst for oxidation of olens and
5
suldes. The study explored the application of Keplerate-
polyoxometalates and made title methodologies suitable for
industrial goals.
On the other hand, as important and versatile synthetic
intermediates, heterocyclic N-oxides of pyridines are used
widely in elds of chemistry and biology. They can be used as
protecting groups, auxiliary agents, oxidants, catalysts, surro-
gates for heterocyclic boronic acids and ligands in metal
6
complexes. Catalytic oxidations of pyridines to N-oxides using
College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University,
Nanyang 473061, China. E-mail: zhaowei1231@163.com; Fax: +86-377-63525055;
Tel: +86-377-63525056
†
Electronic supplementary information (ESI) available: Further experimental and
characterization of oxidation products. See DOI: 10.1039/c5ra05196g
Scheme 1
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Table 1 Oxidation of pyridines to N-oxides with hydrogen peroxide to mono-substituted pyridines, longer reaction time was
a
catalyzed by {Mo132
}
necessary during oxidation of di-substituted pyridines (entries 6
and 7).
b
Entry Substrate
Product
Reaction time (h) Yield (%)
Interestingly, high to excellent yields of corresponding N-
oxides were obtained in this catalytic system at room tempera-
ture during oxidation of quinoline and its derivatives, contain-
ing quinoline, isoquinoline and 8-hydroxy-quinoline (Table 1,
entries 8–10). The mixture solvent of water and ethyl alcohol
c
1
6
6
<2
93
played an important role in these reactions. Catalyst of {Mo132
}
was dissolved in aqueous phase containing water and hydrogen
peroxide. However, substrates of quinoline and its derivatives
were hydrophobic which resulted in an unsuccessful contact
between the substrate and the catalyst. The addition of ethyl
alcohol could be signicantly improved the mass transfer in the
medium. So, the oxidation of quinoline and its derivatives were
successfully carried out in the mixed solvent at room
temperature.
To manifest the superiority of this catalytic system, some
similar previous systems catalyzed by polyoxometalates with
hydrogen peroxide were listed with the described system in
Table 2. As shown in the table, for oxidation of pyridine, the
shortest reaction time (6 h) and mild reaction temperature (298
K) were required in our system. For oxidation of quinoline,
higher reaction temperature was always necessary in previous
systems to improve the catalytic activity. Only in our catalytic
system, quinoline was oxidized to quinoline-N-oxide with high
yield at room temperature. The catalytic activity of Keggin
polyoxomolybdate of phosphomolybdic acid hydrate (H3-
2
3
4
6
6
94
92
5
6
90
6
7
10
10
86
85
2
PMo12O40$xH O) has also been checked for oxidation of pyri-
dine and quinoline (listed in Table 2). Under same reaction
conditions, only 42% and 39% yields of corresponding N-oxides
were obtained when oxidation of pyridine and quinoline cata-
lyzed by phosphomolybdic acid. Based on the above descrip-
tions, we can see that our method is superior to the most of the
previously reported methods.
The catalyst could be reused in this catalytic system. During
reaction, the catalyst dissolved in aqueous phase and catalyzed
the oxidation of pyridines. Aer reaction, the organic product
was separated from the aqueous phase by extraction. The
catalyst was still remained in the aqueous solution aer
extraction, and the aqueous phase could be directly used for the
next run. For oxidation of quinolines, part of catalyst could be
precipitated from medium because of property of substrates
and products. Aer reaction, ltration was carried out before
extraction. The obtained catalyst could be added into the
aqueous phase aer washed and dried when used for next
oxidation. The reuse performances of {Mo132} in the oxidation of
8
9
24
24
84
90
1
0
24
89
a
Reaction conditions: 1 mmol substrate, 5 mmol (30% aq.) H
mmol catalyst, H
temperature (298 K). Isolated yields; assignments of products were
2 2
O , 0.01
2
O (3 ml), absolute ethyl alcohol (2 ml); room
b
1
13
c
analyzed by H NMR and C NMR. Without catalyst.
2-picoline are shown in Fig. 1. Aer ve consecutive reused, there
experiment was also carried out to reveal that the oxidation of was no signicant loss of initial catalytic activity. The yield of N-
pyridine was hardly processed without catalyst (<2%, entry 1). oxide obtained with the recovered catalyst was nearly the same as
Most of the substrates were successfully oxidized to the corre- that of the rst reaction, indicating that catalyst {Mo132} is a
sponding N-oxides in high yields. Selectivities to the products of reusable and robust catalyst in the oxidation system.
N-oxides were $99%. It was found that 2-picoline, 3-picoline
The IR spectra of the catalyst before and aer oxidation have
and 4-picoline were converted to the corresponding N-oxides in been listed in ESI.† As shown in Fig. S1,† there were obvious
excellent yields without obvious differences during 6 h (entries differences in the IR spectra between the fresh catalyst and the
3–5). Di-substituted pyridine derivatives of 2,6-lutidine and 2,3- used catalyst, indicating that the structure of the catalyst aer
lutidine were also examined in this catalytic system. Compared reaction has been changed. Several reports have proved that
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Table 2 Catalytic activity in oxidation of pyridine and quinoline in different systems
Reaction
Reaction temperature (K)
Reaction time (h)
Yield (%)
System
3
2
2
2
2
3
3
2
2
2
48
98
98
98
98
48
38
98
98
98
7
12
16
6
6
7
96
91
96
93
42
82
95
29
84
39
Ref. 8a
Ref. 8b
Ref. 8c
This work
This work
Ref. 8a
Ref. 8b
Ref. 8b
This work
a
6
24
24
24
a
This work
a
Phosphomolybdic acid hydrate used as catalyst.
substrates catalyzed by peroxo species nished, the catalyst
would change back to the polyoxomolybdate species, which
could be used for the next oxidation.
Conclusions
In conclusion, an effective, reusable and mild catalytic system
for pyridine oxidation has been developed based on a Keplerate
polyoxomolybdate. Pyridine and pyridine derivatives were effi-
ciently oxidized to the corresponding N-oxides in high yields at
room temperature during short time. Even some hydrophobic
substrates were successfully oxidized to N-oxides with high
yields at room temperature which required high reaction
temperature in other reported catalytic systems. In addition,
productions could be obtained simply, and the catalyst reused
aer reaction was retentive of catalytic performance.
Fig. 1 Recycling of the catalytic system for oxidation of 2-picoline.
polyoxometalates are not stable in the presence of hydrogen
peroxide. The spectrum of {Mo132} treated with H
been listed in Fig. S2,† indicating that the structure of catalyst
2 2
used in the system would change when reacted with H O .
2 2
O has also
Polyoxometalate catalysts would be transformed into peroxo
species during reaction by hydrogen peroxide have been
1,4,10
reported in the past years.
In addition, the spectrum of Experimental
precipitated solid during oxidation of quinoline was also listed
in ESI (Fig. S3†). The used catalyst and precipitated compound
aer oxidation of quinoline may all belongs to poly-
oxomolybdate species, which were produced aer decomposi-
tion of {Mo132} by hydrogen peroxide. However, both of them
Preparation of catalyst
VI
V
9
[
(NH
Firstly, 5.6 g (4.5 mmol) of (NH
mmol) of CH COONH were dissolved in 250 ml of water with
stirring. 0.8 g (6.1 mmol) of N $H SO was then added to the
4
)
42[Mo72 Mo60
O
372(CH
3
COO)30(H
2
O)72]({Mo132})
4
)
6
Mo 24$4H
7
O
2
O and 12.5 g (162
3
4
1
2
H
4
2
4
have catalytic activity for oxidation. The H NMR spectrum of
solution. The solution was then stirred for 10 min and the color
changed to blue green. 83 ml of CH COOH (50%) was subse-
fresh catalyst has been detected (shown in ESI†). The signals
11
3
were consistent with the previous report. The large signal at
.79 ppm is due to solvent of water; the signal at 7.26 ppm is due
quently added. The deep green solution was kept at 293–298 K
without further stirring for four days (color change to dark
brown). The precipitated red-brown crystals were ltered
through a glass frit (G2). The sample was washed with 90%
ethanol, then with a 1 : 1 mixture of ethanol/diethyl ether and
4
+
to NH ; the signal at 1.99 ppm is due to free ligand of acetate;
4
the signals at 1.03 and 0.84 ppm are due to coordinated species
of acetate. There were no obvious signals of acetate have been
detected in the NMR of recovered catalyst. The results also
indicate that the structure of recovered catalyst aer reaction
has been changed, which is consistent with IR spectra.

nally dried in air. The yield is about 3.2 g (about 50% yield
À1
based on molybdate). IR spectrum (KBr, cm ): 1624, 1540.9,
1
4
401.8, 968.6, 937.0, 856.6, 794.8, 727.1, 631.6, 567.8, 512.8,
64.2, 438.5, 409.5.
According to the experimental data and referencing the
10
reported systems, we presumed a possible mechanism for
pyridine oxidation in this system. When treated with hydrogen
peroxide, {Mo132} will change to several polyoxomolybdate
Catalytic reaction
species. The species could become active peroxo molybdate Catalyst (0.01 mmol), H O (3 ml), absolute ethyl alcohol (2 ml),
2
species during reaction, which is active and responsible for the substrate (1 mmol), and H O (5 mmol, 30% aq.) were charged
2
2
oxidation of pyridines. Exactly, the Keplerate polyoxomolybdate in the reaction ask. The mixture was then stirred at room
used in the system is a precatalyst. When the oxidation of temperature (298 K) for 6–24 h. The reaction was detected by
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TLC. Aer reaction, the organic products were separated from
the aqueous phase by extraction with dichloromethane. The
combined organic layers were dried over anhydrous Na SO ,
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2
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and the pure products were obtained by evaporation or column
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This work was nancially supported by the National Natural
Science Foundation of China (Grant no. 21443007) and the
Natural Science Foundation of Nanyang Normal University (no.
QN2014015).
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