Mild and recyclable catalytic oxidation of pyridines to N-oxides with H2O2 in water mediated by a vanadium-substituted polyoxometalate

Article abstract of DOI:10.1039/c1gc15213k

A vanadium-substituted polyoxometalate, K₆[PW₉V ₃O₄₀]·4H₂O, was used as a recyclable and effective catalyst for the oxidation of pyridines. The reactions were successfully conducted in water under mild conditions. The catalyst could be easily recovered and reused.

Full text of DOI:10.1039/c1gc15213k

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Mild and recyclable catalytic oxidation of pyridines to N-oxides with H2O2
in water mediated by a vanadium-substituted polyoxometalate†
Yong Ding,* Wei Zhao, Wenfeng Song, Zhenxin Zhang and Baochun Ma*
Received 26th February 2011, Accepted 28th March 2011
DOI: 10.1039/c1gc15213k
A vanadium-substituted polyoxometalate, K6[PW9V3O40]·
4H2O, was used as a recyclable and effective catalyst for
the oxidation of pyridines. The reactions were successfully
conducted in water under mild conditions. The catalyst
could be easily recovered and reused.
of K6[PW9V3O40]·4H2O as an effective and recyclable catalyst
for the oxidation of pyridines in water at room temperature. The
process is outlined in Scheme 1. After reaction, the products
were separated from the aqueous phase by extraction, and the
aqueous solution containing the catalyst could be used for the
next cycle.
Heterocyclic N-oxides have important roles in the field of
chemistry because of their wide usefulness in organic synthesis.
Pyridine N-oxide derivatives are used as protecting groups,
auxiliary agents, oxidants, catalysts, surrogates for heterocyclic
boronic acids and ligands in metal complexes.1–4 They are usually
prepared by oxidation of pyridines using peracids,5,6 H2SO5,7
dioxiranes8 and magnesium monophthalate.9 Recently, aqueous
hydrogen peroxide as cheap and clean oxidant with active
catalysts has been developed to minimize waste production and
meet the requirement of green chemistry. Several homogeneous
catalytic systems showed high activity for the oxidation of
pyridines with hydrogen peroxide,10–15 but the catalysts in these
reaction systems are not recyclable. Many heterogeneous cata-
lysts were also successfully demonstrated for the oxidation.16–18
However, in these systems, the reaction conditions are not mild.
Furthermore, high reaction temperature and poisonous organic
solvents are usually required. So the design of a new recyclable,
effective and mild catalytic system for the oxidation of pyridines
is necessary.
Polyoxometalates, as the effective catalysts for oxidation
reaction with hydrogen peroxide have drawn wide atten-
tion in the past years.19–31 But only a few papers have
dealt with the oxidation of pyridines.32,33 Recently, we re-
ported a temperature-controlled phase transfer catalyst of
[(C18H37)2(CH3)2N]7[PW11O39] for pyridine oxidation.34 The cat-
alyst could be recovered by temperature controlling. However, in
this system, high reaction temperature and organic solvent were
required. Here, we find a vanadium-substituted polyoxometalate
Scheme 1
Initially, 4-picoline was used as a model substrate to check the
feasibility of oxidation using 30% hydrogen peroxide as oxidant.
As shown in Table 1, the reaction proceeded very well in water
in the presence of catalytic amount of K6[PW9V3O40]·4H2O
at room temperature. An excellent yield of 4-picoline-N-oxide
(92%) was obtained with an exclusive selectivity (Table 1, entry
9). Some control experiments were also conducted in water
with H2O2 at room temperature for the oxidation of 4-picoline.
Only 6% yield was observed in the absence of catalyst (entry
1). The oxidation proceeded sluggishly by using NaVO3·2H2O,
Table 1 Oxidation of 4-picoline in water with H2O2 mediated by
different catalystsa
Entry
Catalyst
Time (h)
Yieldb (%)
TON
1
2
3
4
5
—
24
24
24
24
24
6
—
17
14
94
81
NaVO3·2H2O
12
10
66
57
Na2HPO4·12H2O
Na2WO4·2H2O
Na2WO4·2H2O +
Na2HPO4·12H2O +
NaVO3·2H2O
6
Na2HPW12O40·xH2O
H4SiW12O40·xH2O
K6H[SiW9V3O40]·3H2O
K6[PW9V3O40]·4H2O
K6[PW9V3O40]·4H2O
24
24
24
16
16
80
77
56
92
0
115
110
80
131
0
7
8
Key Laboratory of Nonferrous Metals Chemistry and Resources
Utilization of Gansu Province, State Key Laboratory of Applied Organic
Chemistry and College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China.
E-mail: dingyong1@lzu.edu.cn, mabaochun@lzu.edu.cn;
Fax: +86-931-8912582; Tel: +86-931-8619200
† Electronic supplementary information (ESI) available: Further ex-
perimental and characterization of oxidation products. See DOI:
10.1039/c1gc15213k
9
10c
a Reaction conditions: 2 mmol substrate, 10 mmol (30% aq.) H2O2,
14 mmol catalyst, 1 ml H2O, room temperature. TON = molar of
product/molar of catalyst used. b Yields were determined by GC
analysis. Assignments of products were analyzed by H NMR and 13C
1
NMR. c Without adding H2O2.
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Table 2 Oxidation of 4-picoline with H2O2 mediated in different
Table 3 Oxidation of pyridines with H2O2 catalyzed by
solventa
K6[PW9V3O40]·4H2O in watera
Entry
Solvent
Yieldb (%)
TON
Entry Substrate
Product
Time (h)
8
Yield (%) TON
1
2
3
4
5
6
7
H2O
ethanol
acetonitrile
acetone
ethyl acetate
toluene
92
13
27
37
52
79
74
131
18
38
53
74
113
106
1
84
91
120
130
2
12
trichloromethane
a Reaction conditions: 2 mmol 4-picoline, 10 mmol (30% aq.) H2O2,
14 mmol catalyst of K6[PW9V3O40]·4H2O, 1 ml solvent, room tempera-
ture, reaction time: 16 h. b Yields were determined by GC analysis.
3
4
12
16
93
90
133
128
Na2WO4·2H2O, Na2HPO4·12H2O or the simple mixture of
them as catalyst (entries 2–5). In addition, some keggin-type
polyoxometalates (entries 6–8) were also used and it was found
that K6[PW9V3O40]·4H2O exhibited the highest activity among
all the examined catalysts, indicating the special activity of this
vanadium-substituted polyoxometalate.
5
6
16
24
92
90
131
128
The effect of the solvent on the activity of the catalyst
was investigated, and the results are listed in Table 2. It
was found that water was proven to be the best solvent for
the oxidation. The activities of the catalyst in other organic
solvents were not satisfied. The conversions of 4-picoline to 4-
picoline-N-oxide performed in ethanol, acetonitrile and acetone
were less than 37% (entries 2–4). But in ethyl acetate, toluene
and trichloromethane, the yields of the products were much
higher (entries 5–7). These results should be attributed to
the solubility of the catalyst in these solvents. The catalyst,
K6[PW9V3O40]·4H2O, is an inorganic salt that has a potassium
cation as the counter cation. It was dissoluble in the hydrogen
peroxide aqueous phase during the reaction. The organic
solvents, ethanol, acetonitrile and acetone, could be dissoluble
in aqueous solution. These hydrophilic solvents made that the
catalyst partly precipitated from the aqueous phase. So no
significant activity was observed in these solvents. In contrast,
the hydrophobic solvents, such as ethyl acetate, toluene and
trichloromethane, had no effect on the solubility of the catalyst.
Therefore, moderate yields was obtained in these cases. The
solubility of the catalyst in the system played an important role
during the oxidation. It is noteworthy that this catalytic system
based on K6[PW9V3O40]·4H2O in water is more effective than
other systems.
7
8
24
24
92
43
131
61
9
24
6
29
95
41
10b
136
11b
12b
6
6
97
97
138
138
Having obtained these results, we extended our catalytic
system to the oxidation of other pyridine derivatives. Table 3
summarizes the results of catalytic oxidation of pyridine and
pyridine derivatives based on K6[PW9V3O40]·4H2O with 30%
H2O2. Most of the substrates were successfully oxidized to the
corresponding N-oxides in high yields at room temperature. For
pyridine, a yield of 84% was obtained within 8 h catalyzed by
K6[PW9V3O40]·4H2O (Table 3, entry 1). When the reaction time
proceeded to 12 h, the yield of pyridine N-oxide reached up
to 91% (entry 2). The effect of the –CH3 position in picolines
were also examined. It was found that 2-picoline was more
reactive toward the oxidation than 3-picoline and 4-picoline.
An excellent yield (93%) of 2-picoline-N-oxide was obtained
within 12 h (entry 3). However, there was no obvious difference
a Reaction conditions: 2 mmol substrate, 10 mmol (30% aq.) H2O2,
14 mmol catalyst, 1 ml H2O. Room temperature. Yields were determined
1
by GC analysis. Assignments of products were analyzed by H NMR
and 13C NMR. b Reaction temperature: 65 ◦C.
between 3-picoline and 4-picoline. Both of them were converted
to the corresponding N-oxides in excellent yields with an
increased reaction time, 16 h (entries 4 and 5). Di-substituted
pyridine derivatives were also examined in this catalytic system.
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2,6-Lutidine and 2,3-lutidine were more difficult to be oxidized
than monosubstituted pyridines, but we are able to obtain the
corresponding N-oxides in excellent yields within 24 h by using
K6[PW9V3O40]·4H2O as catalyst (entries 6 and 7). Electron-
deficient substrate, such as 2-chloropyridine, was hardly reactive
as expected (entry 8). The oxidation of quinoline and its
derivatives were also determined in water. A low yield (29%)
of quinoline-N-oxide was obtained after 24 h of reaction at
room temperature. However, when the reaction temperature
increased to 65 ◦C, quinoline was successfully converted to the
N-oxide with an excellent conversion within 6 h (entries 9 and
10). This improvement might be particularly attributed to the
effect of the hydrophobicity of the substrate. The poor solubility
of quinoline in water at room temperature resulted in an
unsuccessful contact between the substrate and the catalyst. But
the mass transfer could be significantly improved by elevating
the reaction temperature to 65 ◦C, thus the performance of the
catalyt was improved. This phenomenon was also observed in
the oxidation of other quinoline derivatives. Isoquinoline and
4-methyl-quinoline were also oxidized to the corresponding N-
oxides with excellent yields (entries 11 and 12) at 65 ◦C during
6 h.
Fig. 1 IR spectra of the catalyst before and after oxidation reaction:
(a) the fresh catalyst; (b) the used catalyst.
The active catalyst could be easily reused in this catalytic
system. During reaction, the catalyst dissolved in aqueous
phase and catalyzed the oxidation of pyridines. After reaction,
the organic product was separated from the aqueous phase
by extraction. The catalyst was still remained in the aqueous
solution after extraction, and the aqueous phase could be
directly used for the next run. The reuse performance of
K6[PW9V3O40]·4H2O in the oxidation of pyridine are also shown
in Table S1 (see ESI†). Yield of pyridine-N-oxide obtained with
the recovered catalyst was nearly the same as that of the first
reaction (91%), indicating that K6[PW9V3O40]·4H2O is a reusable
and robust catalyst in the oxidation system.
Fig.
2
31P MAS NMR spectra of: (a) the fresh catalyst of
K6[PW9V3O40]·4H2O; (b) the used catalyst.
The fresh catalyst of K6[PW9V3O40]·4H2O and the used
catalyst were characterized with FT-IR spectra (Fig. 1). The
IR spectrum of K6[PW9V3O40]·4H2O exhibited peaks at 1085,
1055, 959, 877 and 789 cm-1, which was similar with the previous
report.35 Comparing the IR spectrum of the used catalyst with
that of the fresh catalyst, the characteristic peaks were still
existed and no fresh peak appeared. There was no discernable
difference between the IR spectra of the fresh catalyst and the
used one, indicating that the structure of the active catalyst was
stable during the reaction. 31P MAS NMR was also used to
characterize the fresh catalyst and the used one (Fig. 2). A
strong peak at -13.2 ppm is shown in Fig. 2a. It should be
attributed to the structure of [PW9V3O40]6-. The results in 31P
MAS NMR were consistent with the IR characterization. As
shown in Fig. 2b for the used catalyst, a single peak at -13.2 ppm
was observed without obvious difference with the fresh catalyst.
All these results revealed that the structure of the catalyst did
not change after the oxidation. According to some reported
mechanisms about the oxidation reaction using vanadium
substituted polyoxometalate with hydrogen peroxide,36–38 we
proposed a possible procedure for the oxidation of pyridines
catalyzed by K6[PW9V3O40]·4H2O in water with H2O2 (shown in
Fig. 3). First, the compound of trivanadium-substituted polyox-
ometalate reacts with hydrogen peroxide to form peroxotungsten
species and peroxovanadium species. These peroxo species are
Fig. 3 Proposed mechanism for the oxidation of pyridines catalyzed
by K6[PW9V3O40]·4H2O.
quite active and might play an important role in determining
the activity of the catalyst. Then, the intermediate delivers an
active oxygen to the substrates and oxidizes pyridines to the
corresponding heterocyclic N-oxides. Simultaneously, a keggin
trivanadium-substituted polyoxometalate was regenerated. So,
there was no obvious difference between the structure of the
fresh catalyst and the used one.
In summary, an effective, recyclable and mild catalytic system
has been developed for the oxidation of pyridines with hydrogen
peroxide based on a vanadium-substituted polyoxometalate.
1488 | Green Chem., 2011, 13, 1486–1489
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Pyridine and pyridine derivatives were efficiently oxidized to the
corresponding N-oxides in high yields under mild conditions.
After reaction, the products were separated from the system by
extraction. The catalyst dissolved in aqueous phase could be
used for the next run. This system is an environmentally friendly
and reusable oxidation system for pyridine oxidation.
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This work was financially supported by the National Natural
Science Foundation of China (Grant Nos. 20702021, 20803032).
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state NMR and Prof. Yanlong Gu for his valuable discussions.
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