Green and reusable synthetic procedure for pyridine N-oxides catalyzed by a lacunary polyoxometalate

Article abstract of DOI:10.1080/00397911.2013.796524

A lacunary Keggin polyoxometalate of K8[BW11O39H] · 13H2O was used as an effective and reusable catalyst for pyridine oxidation. Good yields of pyridine N-oxides were obtained in this catalytic system with hydrogen peroxide in water under mild conditions. Taylor and Francis Group, LLC.

Full text of DOI:10.1080/00397911.2013.796524

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Green and Reusable Synthetic Procedure
for Pyridine N-Oxides Catalyzed by a
Lacunary Polyoxometalate
a
b
a
Wei Zhao , Xing Wang & Chunxia Yang
a
College of Chemistry and Pharmaceutical Engineering, Nanyang
Normal University , Nanyang , China
b
School of Software, Nanyang Normal University , Nanyang , China
Accepted author version posted online: 15 Aug 2013.Published
online: 11 Oct 2013.
To cite this article: Wei Zhao , Xing Wang & Chunxia Yang (2014) Green and Reusable
Synthetic Procedure for Pyridine N-Oxides Catalyzed by a Lacunary Polyoxometalate, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
44:1, 150-160, DOI: 10.1080/00397911.2013.796524
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1
Synthetic Communications , 44: 150–160, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.796524
GREEN AND REUSABLE SYNTHETIC PROCEDURE FOR
PYRIDINE N-OXIDES CATALYZED BY A LACUNARY
POLYOXOMETALATE
1
Wei Zhao, Xing Wang, and Chunxia Yang
2
1
1
College of Chemistry and Pharmaceutical Engineering,
Nanyang Normal University, Nanyang, China
2
School of Software, Nanyang Normal University, Nanyang, China
GRAPHICAL ABSTRACT
Abstract A lacunary Keggin polyoxometalate of K
8
[BW11
O
39H] ꢀ 13H
2
O was used as an
effective and reusable catalyst for pyridine oxidation. Good yields of pyridine N-oxides were
obtained in this catalytic system with hydrogen peroxide in water under mild conditions.
[Supplementary materials are available for this article. Go to the publisher’s online
1
edition of Synthetic Communications for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Catalysis; green; polyoxometalate; pyridine-N-oxide; reusable
INTRODUCTION
Pyridine N-oxides are important and versatile synthetic intermediates, which
are used widely in fields of chemistry and biology. They can be used as protecting
groups, auxiliary agents, oxidants, catalysts, surrogates for heterocyclic boronic
[
1–5]
acids, and ligands in metal complexes.
In addition, pyridine N-oxide derivatives
6]
[
have been reported to represent a new class of anti-HIV compounds. In the past,
pyridine N-oxides were usually prepared by noncatalytic oxidation of pyridines
[7–9]
using strong oxidants.
The oxidation of pyridines was also represented high
Received February 25, 2013.
Address correspondence to Wei Zhao, College of Chemistry and Pharmaceutical Engineering,
Nanyang Normal University, Nanyang 473061, China. E-mail: zhaowei1231@163.com
1
50

GREEN SYNTHESIS OF PYRIDINE N-OXIDES
151
Scheme 1. Process of pyridine oxidation in water catalyzed by K
10,11]
8
[BW11
O
39H] ꢀ13H
2
O.
[
activity in the presence of peracetic acid or acetic acid.
However, the by-product
for pyridine oxidation in the presence of acetic acid or peracetic acid is acetic acid,
which is corrosive for the equipment and environment. Besides, peracetic acid used
as oxidant is also dangerous during the reaction because of risk of explosion. For
green chemistry, hydrogen peroxide as a mild oxidant is used widely in catalytic oxi-
dations. Catalytic oxidation using homogeneous catalysts with hydrogen peroxide of
pyridines to N-oxides has received much attention in recent years. Such catalysts
[
12]
[13]
include AcOH=H O ,
2
MeReO =H O ,
2
trifluoroacetic anhydride (TFAA)=
2
3
2
[15]
[
14]
H O , and Tf O=Na CO ꢀ 1.5H O . To overcome the difficulties of the catalyst
2
2
2
2
3
2
2
[
16]
recycling, several heterogeneous catalysts including perfluoroketone-silicate,
and V Si O
[
17]
[18]
TS-1,
were also demonstrated for the oxidation of pyridines.
x
4x 6.4x
However, in these recovered catalytic systems, 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 pyridine is necessary.
Polyoxometalates (POMs) have been used widely as effective catalysts for liquid
oxidations with hydrogen peroxide, such as olefin epoxidation, alcohol oxidation, and
[
19–30]
so on. Reports about oxidation of pyridines using POMs with hydrogen
peroxide are less,
were necessary in these procedures. Recently, a vanadium-substituted POM,
[5,31,32]
and high reaction temperatures or poisonous organic solvents
K [PW V O ] ꢀ 4H O, was used as a recyclable and effective catalyst for the oxi-
6
9
3
40
2
[
33]
dation of pyridines. The reactions were successfully conducted in water under mild
conditions. However, the substituted metal of vanadium was necessary in the POM
catalyst. To expand the applications of POMs in water for oxidation of pyridines
under mild temperature, here we report a nonsubstituted lacunary POM
(
K [BW O H] ꢀ 13H O) as an effective catalyst for the oxidation of pyridines. The
8
11 39
2
oxidation was carried out in water under room temperature, and good yields of
N-oxides were obtained. Recently, some significant progress has been achieved,
ranging from oxidation of organic compounds, which is environmentally benign,
or green catalytic oxidation using the big class of POMs as catalysts, especially for
[34]
[35]
detoxification of toxic industrial chemicals and photocatalytic water oxidation.
The system in this article is consistent with green environmental science; the solvent of
water and the mild reaction temperature (room temperature) is green and environ-
mentally benign. The process is outlined in Scheme 1. The catalyst can be reused
several cycles without obvious loss in activity.
RESULTS AND DISCUSSION
The catalytic oxidations of 4-picoline using different catalysts in water are
shown in Table 1. The reaction proceeded very well in water in the presence of a
catalytic amount of K [BW O H] ꢀ 13H O at room temperature. An excellent yield
8
11 39
2

152
W. ZHAO, X. WANG, AND C. YANG
a
Table 1. Oxidation of 4-picoline using different catalysts in water
b
Yield (%)
Entry
Catalyst
Time (h)
1
2
3
4
no
24
24
24
24
16
16
24
24
5
8
H
3
BO
3
Na
2
WO
4
ꢀ 2H
2
O
WO
68
65
0
H
3
K
8
K
8
K
7
K
8
BO
3
þ Na
2
4
ꢀ 2H
2
O
c
5
[BW11
O
39H] ꢀ 13H
2
O
6
7
8
[BW11
O39H] ꢀ 13H
2
O
92
87
82
PW11
O39 ꢀ 12H
2
O
[b-SiW11
O39] ꢀ 14H
2
O
a
Reaction conditions: 0.03 mmol catalyst; 3 ml water; 4 mmol substrate;
; reaction temperature: room temperature. Assign-
20 mmol (30% aq.) H
ments of products were analyzed by H NMR and C NMR.
2
O
2
1
13
b
Isolated yields.
c
2 2
Without H O .
of 4-picoline-N-oxide (92%) was obtained with an exclusive selectivity (Table 1,
entry 6). Some control experiments were also conducted in water with H O at
2
2
room temperature for the oxidation of 4-picoline. Only 5% yield was observed in
the absence of catalyst (entry 1), and the reaction was hardly processed without
hydrogen peroxide (entry 5). The oxidation proceeded sluggishly using H BO ,
3
3
Na WO ꢀ 2H O, or the simple mixture of H BO and Na WO ꢀ 2H O. In addition,
2
4
2
3
3
2
4
2
some keggin-type POMs (entries 7, 8) were also used, and it was found that they
exhibited less activity than K [BW O H] ꢀ 13H O, indicating the special activity
8
11 39
2
of this lacunary POM.
Having obtained these results, we extended this catalytic system to the oxidation
of other pyridine derivatives. The results are listed in Table 2. Most of the substrates
were successfully oxidized to the corresponding N-oxides in good yields at room
temperature. Selectivities to the N-oxides were ꢁ99%. For pyridine, a yield of 95%
was obtained within 16 h catalyzed by K [BW O H] ꢀ 13H O in water at room tem-
8
11 39
2
perature (Table 2, entry 1). The substrates of picolines were also examined. It was
found that 2-picoline, 3-picoline, and 4-picoline were converted to the corresponding
N-oxides in excellent yields with an appropriate reaction time (entries 2–4). Disubsti-
tuted pyridine derivatives were also examined in this catalytic system. 2,6-Lutidine
and 2,3-lutidine were more difficult to oxidize than monosubstituted pyridines, and
the results might be attributed to their comparative hydrophobicity compared with
monosubstituted pyridines. We are able to obtain the corresponding N-oxides in
excellent yields within 24 h by using K [BW O H] ꢀ 13H O as catalyst (entries 5
8
11 39
2
and 6). The electron-deficient substrate 2-chloropyridine was less reactive, as expected
ꢂ
(
entry 7). Even if the reaction temperature elevated to 65 C, 2,6-pyridinedicarboxylic
acid was hardly reactive because of its electron-deficient property and the hydro-
phobic of the substrate (entry 8). The oxidation of quinoline was also determined
in water. A poor yield of quinoline-N-oxide was obtained after 24 h of reaction at
room temperature in water (not listed here). However, when the reaction temperature
ꢂ
increased to 65 C, quinoline was successfully converted to the N-oxide with an excel-
lent conversion within 7 h (entry 9). This improvement might be partially attributed
to the effect of the hydrophobicity of the substrate. The poor solubility of quinoline in

GREEN SYNTHESIS OF PYRIDINE N-OXIDES
Table 2. Oxidation of pyridine derivatives with H catalyzed by K [BW11
Reaction
153
a
2
O
2
8
O
39H] ꢀ 13H
2
O
b
Time Yield
ꢂ
Entry
Substrate
Product
temperature ( C)
(h)
16
(%)
95
1
25
2
3
25
25
16
16
90
92
4
5
6
7
8
25
25
25
65
65
24
24
24
6
94
90
93
38
6
<5
(
Continued )

154
W. ZHAO, X. WANG, AND C. YANG
Table 2. Continued
b
Reaction
temperature ( C)
Time Yield
(h)
ꢂ
Entry
Substrate
Product
(%)
9
65
6
90
1
1
0
1
65
65
6
6
88
87
a
Reaction conditions: 0.03 mmol K
8
[BW11
O
39H] ꢀ 13H
2
O; 3 ml water; 4 mmol substrate; 20 mmol (30%
1
2 2
aq.) H O ; reaction temperature: room temperature. Assignments of products were analyzed by H NMR
1
and C NMR.
b
3
Isolated yields.
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
ꢂ
the reaction temperature to 65 C, and thus the performance of the catalyst was
improved. This phenomenon was also observed in the oxidation of other quinoline
derivatives. Isoquinoline and 4-methyl-quinoline were also oxidized to the corre-
ꢂ
sponding N-oxides with good yields (entries 10 and 11) at 65 C during 6 h.
To show the efficiency and applicability of this method, our results have been
compared with some of the recently reported methods on the oxidation of 4-picoline,
which is carried out in water catalyzed by polyoxometalates. As shown in Table 3,
some Keggin-type polyoxometalates (entries 1–3) were also used as catalysts for oxi-
dation of 4-picoline, indicating the greater catalytic activity of K [BW O H] ꢀ 13H O.
8
11 39
2
Table 3. Comparison of results for oxidation of 4-picoline catalyzed by different catalysts
Reaction Reaction Yield
ꢂ
Catalyst
temperature ( C) time (h)
(%)
Remark
Na
2
HPW12
SiW12
40 ꢀ xH
H[SiW
40] ꢀ 3H
(H O) (ZnW
40] ꢀ 4H
39H] ꢀ 13H
O
40 ꢀ xH
2
O
25
25
25
75
25
25
24
24
24
7
82
78
60
43
92
92
—
—
—
H
K
4
6
O
2
O
9
V
3
O
2
O
[
31]
Na12[WZnZn
2
2
2
O
9 34
)
2
]
Ref. , zinc-substituted
[33]
K
K
6
[PW
9
V
3
O
2
O
16
16
Ref. , vanadium-substituted
This work, nonsubstituted
lacunary
8
[BW11
O
2
O

GREEN SYNTHESIS OF PYRIDINE N-OXIDES
155
Table 4. Oxidation of 4-picoline using K
a
under different solvents
8
[BW11
2
O39H] ꢀ 13H O
b
Yield (%)
Entry
Solvent
1
2
3
4
5
Ethanol
47
40
48
82
92
Acetonitrile
Chloroform
Ethyl acetate
Water
a
Reaction conditions: 0.03 mmol
K
8
[BW11
O
39H] ꢀ 13H
; reac-
tion temperature: room temperature. Assignments of products
2
O;
3
2 2
ml solvent; 4 mmol substrate; 20 mmol (30% aq.) H O
1
13
were analyzed by H NMR and C NMR.
b
Isolated yields.
Compared with the reported water-soluble polyoxometalate catalytic systems, our
method is superior to the most of the previously reported methods (entries 4–6).
Table 4 shows the solvent effect of oxidation of 4-picoline using K [BW O H] ꢀ
8
11 39
1
3H O at room temperature. It was found that water was proven to be the best sol-
2
vent for the oxidation. A 92% yield of 4-picoline-N-oxide was obtained catalyzed by
K [BW O H] ꢀ 13H O in water. The catalytic results were not satisfied in other
8
11 39
2
organic solvents. These results should be attributed to the solubility of the catalyst
in these solvents. The catalyst was insoluble in all of the organic solvents because
of the components of the catalyst. The catalyst precipitated from water with potass-
ium cation by addition of the potassium chloride, so the catalyst was a ‘‘water-
soluble’’ catalyst: It can be dissolved in water but is insoluble in organic solvents.
It is noteworthy that this catalytic system based on K [BW O H] ꢀ 13H O in water
8
11 39
2
is more effective than other systems.
The catalyst could be reused in this catalytic system. After the reaction, the sys-
tem was concentrated by evaporation and then the catalyst was recovered from the
mixture by the addition of anhydrous ethyl alcohol. The recovered catalyst was
washed with anhydrous ethyl alcohol and Et O and then used for the next oxidation.
2
The performance of K [BW O H] ꢀ 13H O in the oxidation of pyridine is shown in
8
11 39
2
Table 5. After three consecutive reuses, the yield of pyridine-N-oxide obtained with
the recovered catalyst was nearly the same as that of the first reaction (95%), indicat-
ing that K [BW O H] ꢀ 13H O is a reusable catalyst in the oxidation system.
8
11 39
2
The fresh catalyst of K [BW O H] ꢀ 13H O, the used catalyst of cycle 1, the
8
11 39
2
used catalyst of cycle 3, and the catalyst treated with hydrogen peroxide were
a
Table 5. Recycling of the catalytic system for the oxidation of 4-picoline
Entry
Cycle
Selectivity (%)
Yield (%)
1
2
3
1
2
3
99
99
99
95
96
95
a
Reaction conditions: 0.12 mmol
6 mmol substrate; 80 mmol (30% aq.) H
K
8
[BW11
O
39H] ꢀ 13H
2
O; 8 ml water;
1
temperature; reaction time: 16 h.
2 2
O ; reaction temperature: room

156
W. ZHAO, X. WANG, AND C. YANG
characterized with Fourier transform–infrared (FT-IR) spectra (the spectrum of the
used catalyst of cycle 2 is nearly the same as that of cycle 3). As shown in Fig. 1, there
existed differences in IR spectrum between the fresh catalyst and used one, indicating
that the structure of the fresh catalyst has been changed during the oxidation. The
8
ꢃ
[36]
relative instability of polyoxotungstate anion of [BW O H] has been reported.
39
1
1
8
The conversions between the species of [BW O H] , [BW O H ] , and
[B W O132] are rapid and reversible. The formation of the other heteropolyanions
3 39
could be observed by treatment of the [BW O H] aqueous solution. The recov-
ꢃ
8ꢃ
1
1
39
13 46
3
2
1-
8
ꢃ
1
1
39
ered catalyst after first oxidation is a mixture of several heteropolyanions, so the IR
spectrum of it is different from the pure K [BW O H] ꢀ 13H O. By comparing the
8
11 39
2
spectra of the used catalyst of cycle 1 with the used catalyst of cycle 3, it can be found
that their structures were similar, indicating that there were no obvious changes from
the first cycle (the spectrum of the used catalyst of cycle 2 is nearly the same as that
ꢃ1
of cycle 3). An obvious peak at 840 cm was appeared in the spectrum of the cata-
[
19]
lyst treated with hydrogen peroxide (Fig. 1b), which was attributed to n (O-O).
The characterization of the ultraviolet–visible technique was taken for the structures
shown in the Supporting Information). The spectrum of the first recycled catalyst
(
was obviously different from that of the fresh one, and similar spectra of the used
catalyst of cycle 1 and the used catalyst of cycle 3 were obtained. The results were
consisted with FT-IR spectra.
There have been many similar cases for the structure changes of POMs during the
They all have similar procedures, which have
[32,33]
oxidation with hydrogen peroxide.
been proved by several characterization methods. According to the characterizations
and the previous report, we proposed a possible mechanism for oxidation of pyridines
catalyzed by K [BW O H]ꢀ 13H O in water with hydrogen peroxide (shown in Fig. 2).
8
11 39
2
During the reaction, the catalyst of K [BW O H] ꢀ 13H O was treated with hydrogen
8
11 39
2
peroxide in water. The heteropolyanion of K [BW O H] ꢀ 13H O became a mixture of
8
11 39
2
Figure 1. IR spectra of the catalyst before and after oxidation reaction: (a) the freshly prepared catalyst;
b) the catalyst treated with H ; (c) the catalyst of cycle 1; and (d) the catalyst of cycle 3.
(
2 2
O

GREEN SYNTHESIS OF PYRIDINE N-OXIDES
157
Figure 2. Possible mechanism for oxidation of pyridines catalyzed by K
8
2
[BW11O39H] ꢀ 13H O in water.
heteropolyanions. Then, the hydrogen peroxide promoted the mixture of heteropolya-
nions formed the tungsten-peroxo intermediate. The active intermediate is quite active
and might be responsible for the oxidation of pyridines to the corresponding N-oxides.
Then, the intermediate delivers active oxygen to the substrates and oxidizes pyridines to
the corresponding heterocyclic N-oxides. Simultaneously, the mixture of heteropolya-
nions after losing their active oxygen oxidation was regenerated.
In summary, a green catalytic system for the synthesis of pyridines N-oxides
has been developed in water with hydrogen peroxide under room temperature based
on a nonsubstituted lacunary polyoxometalate (K [BW O H] ꢀ 13H O). Pyridine
8
11 39
2
and pyridine derivatives were efficiently oxidized to the corresponding N-oxides in
good yields under mild conditions. The catalyst was reused several times without
obvious loss in activity. This system is an environmentally friendly and reusable
oxidation system for pyridine oxidation.
EXPERIMENTAL
[
36]
K [BW O H] ꢀ 13H O was synthesized by the procedure reported in Ref.
8
11 39
2
Catalyst (0.03 mmol), H O (3 ml), substrate (4 mmol), and H O (20 mmol, 30%
2
2
2
aq.) were charged in the reaction flask, which was first bathed in cold water (about
83 K). The mixture was then stirred at room temperature for 16–24 h. The reaction
2
was detected by thin-layer chromatography (TLC). After the reaction, the system
was concentrated by evaporation, and the catalyst precipitated from the mixture
after the addition of anhydrous ethyl alcohol. The recovered catalyst, obtained by
filtration, was washed with anhydrous ethyl alcohol and diethyl ether and then used
for the next oxidation after drying. The filtrate was extracted with dichloromethane.
The combined organic layers were dried over anhydrous Na SO , and the pure pro-
2
4
ducts were obtained by evaporation or column chromatography. The products were
1 13
analyzed by H NMR and C NMR.
SUPPORTING INFORMATION
1
13
Full experimental detail and H and C NMR spectra of pyridine-N-oxides
can be found via the Supplementary Content section of this article’s Web page.

158
W. ZHAO, X. WANG, AND C. YANG
ACKNOWLEDGMENT
This work is supported by the Natural Science Foundation of Nanyang
Normal University (No. ZX2012012).
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