Organic salts of polyoxometalates: Novel and efficient catalysts for the synthesis of pyridine n-oxide derivatives

Article abstract of DOI:10.1080/15533174.2010.522658

Catalytic N-oxidation of pyridine derivatives to related N-oxides were performed in the peresence of three organic salts of polyoxometalates including two heteropolyanion (THA)_7.7H_6.3[NaP₅W ₃₀O₁₁₀], 1, and (THPA)_7.5 H _6.5[NaP₅W₃₀O₁₁₀], 2, and one isopolyanion [TBA]₂[W₆O₁₉] (3) with W as central metal atom. Catalyst (3) showed the best catalytic activity. The highly selective oxidation gave good to excellent yields of the related N-oxides along with decarboxylation at 2-position of pyridine ring. The effect of some operative variables, such as temperature, various solvents, and the reaction time was studied. The reaction conditions were optimized. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/15533174.2010.522658

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Organic Salts of Polyoxometalates: Novel and
Efficient Catalysts for the Synthesis of Pyridine N-
oxide Derivatives
a
a
b
Niloofar Tavakoli-Hoseini , Fatemeh F. Bamoharram & Majid M. Heravi
a
Department of Chemistry, Faculty of Sciences , Islamic Azad University , Mashhad
Branch, Mashhad, I. R. Iran
b
Department of Chemistry, School of Sciences , Azzahra University , Vanak, Tehran, I. R.
Iran
Published online: 03 Dec 2010.
To cite this article: Niloofar Tavakoli-Hoseini , Fatemeh F. Bamoharram & Majid M. Heravi (2010) Organic Salts of
Polyoxometalates: Novel and Efficient Catalysts for the Synthesis of Pyridine N-oxide Derivatives, Synthesis and Reactivity
in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 40:10, 912-915
To link to this article: http://dx.doi.org/10.1080/15533174.2010.522658
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 40:912–915, 2010
Copyright © Taylor & Francis Group, LLC
ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2010.522658
Organic Salts of Polyoxometalates: Novel and Efficient
Catalysts for the Synthesis of Pyridine N-oxide Derivatives
1
1
2
Niloofar Tavakoli-Hoseini, Fatemeh F. Bamoharram, and Majid M. Heravi
1
Department of Chemistry, Faculty of Sciences, Islamic Azad University, Mashhad Branch, Mashhad,
I. R. Iran
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, I. R. Iran
2
ring transformation of isoxazoles and through cycloaddition
Catalytic N-oxidation of pyridine derivatives to related reactions.[11–17] The shortcomings of these methods are the
N-oxides were performed in the peresence of three or- requirement of high temperature or catalyst loading, longer
ganic salts of polyoxometalates including two heteropolyanion
reaction times, expensive and highly toxic catalysts, specific
conditions and tedious work up procedures. Hence, a practical
and more efficient method using inexpensive and environment
(
2
THA)7.7
H
6.3[NaP
5
W
30
O
110], 1, and (THPA)7.5
, and one isopolyanion [TBA] [W 19] (3) with W as central
metal atom. Catalyst (3) showed the best catalytic activity. The
5 30
H6.5[NaP W O110],
2
6
O
highly selective oxidation gave good to excellent yields of the re- friendly catalyst is still of interest. Recently, there has been con-
lated N-oxides along with decarboxylation at 2-position of pyridine siderable interest in the use of heteropolyacids as environmen-
ring. The effect of some operative variables, such as temperature,
various solvents, and the reaction time was studied. The reaction
thermal stability, low cost, ease of preparation, and ease of recy-
conditions were optimized.
tally benign catalysts due to their unique properties such as high
clability. Numerous chemical reactions can be carried out in the
presence of heteropolyacids. Our previous work was devoted
to study the catalytic performance of H14[NaP5W30O110], so
Keywords organic salt, polyoxometalates, pyridine N-oxide, pyri-
dine derivatives
called Preyssler acid, in order to obtain pyridine N-oxides from
pyridine derivatives.[ Therefore, it is of great interest to know
what occurs if in Preyssler acid, organic groups are replaced in-
18]
1.
INTRODUCTION
stead of some acidic protons. We also investigated the catalytic
performance of an isopolytungestate. As part of research project
and in continuation of our researches on polyoxometalates,[
the present work screens the performance of the organic salts
of polyoxometalates as: tetrahexyl ammonium (THA) and tetra-
heptyl ammonium (THPA) with Preyssler, 1 and 2, and tetra-
butylammonium (TBA) hexatungestate (3), in N-oxidation of
pyridine derivatives. To the best of our knowledge, there is not
any report concerning the catalytic behavior of the studied poly-
oxometalates in this work in the oxidation of pyridines.
Pyridine N-oxides belong to a vast class of heterocyclic N-
oxides, many of which are biologically active.[
1,2]
Recently,
19,20]
pyridine N-oxide derivatives represented a new class of anti-
HIV compounds, for which some members exclusively act
through inhibition of HIV reverse transcriptase, and thus char-
acteristically behave as non-nucleoside reverse transcriptase
inhibitors.[3] Interestingly, in the nanotechnology field, it has
been shown that nanoshampoo including carboxylic acid pyri-
dine N-oxide is a very powerful hair growth stimulator with a
[4]
high level of safety. Pyridine N-oxides are also useful as pro-
tecting groups, auxiliary agents, oxidants, ligands in metal com-
[5]
plexes, and catalysts. Many researchers have studied the N-
oxidation of pyridines using various oxidants and catalysts.[6−10]
Pyridine N-oxides are usually prepared by oxidation of pyridines
using peracids such as meta-chloroperbenzoic acid and per-
acetic acid, from the esters of N-hydroxy-2-thiopyridone, by
2. EXPERIMENTAL
2.1. Chemicals and Apparatus
All compounds were known, and their physical and spec-
troscopic data were compared with those of authentic samples
and found to be identical. Melting points were recorded on an
electrothermal type 9100 melting point apparatus. The IR spec-
tra were obtained on a 4300 Shimadzu spectrophotometer as
Received 9 January 2010; accepted 28 July 2010.
The authors are thankful to Islamic Azad University, Mashhad
Branch for financial support.
Address correspondence to Niloofar Tavakoli-Hoseini, Department
of Chemistry, Faculty of Sciences, Islamic Azad University, Mashhad
Branch, Mashhad, I. R. Iran. E-mail: niloofartavakoli@mshdiau.ac.ir
1
KBr disks. The H NMR (100 MHz) spectra were recorded on
a Bruker AC 100 spectrometer. The TG curves were recorded
using TGA-1500 instrument. GC-Mass analysis was performed
on a GC-Mass model: 5973 network mass selective dedector,
912

SYNTHESIS OF PYRIDINE N-OXIDE DERIVATIVES
913
TABLE 1
a
N-oxidation of pyridine derivatives using H2O2 and polyoxometalate catalysts with various solvents
Entry
1
Pyridine
Product
Time (h)
Solvent
% Yield with catalysts (3/2/1)
1
5
5
5
Solvent-free
PhCH3
CH3CN
THF
95/trace/trace
70/72/88
74/46/40
72/85/75
2
3
1
5
5
5
Solvent-free
PhCH3
CH3CN
THF
93/trace/trace
71/70/86
75/32/36
73/84/72
1
6
6
5
Solvent-free
PhCH3
CH3CN
THF
90/trace/trace
78/80/77
82/28/33
78/85/91
4
5
6
1
.30
6
Solvent-free
PhCH3
CH3CN
THF
88/trace/trace
75/81/87
80/25/27
5
5
73/82/74
1
4
.30
4
Solvent-free
PhCH3
CH3CN
THF
96/trace/trace
88/84/97
78/trace/trace
68/86/75
4
1
Solvent-free
PhCH3
CH3CN
THF
92/trace/trace
82/80/88
84/26/18
4
4
.30
.30
5
72/89/78
7
1
5
5
.30
Solvent-free
PhCH3
CH3CN
THF
55/trace/trace
48/trace/trace
46/15/12
5
52/27/16
a
◦
Reaction conditions: pyridine (5 mmol), hydrogen peroxide (7.5 mL), catalyst (0.05 mol), solvent (10 mL), reflux, neat (90 C).
GC 6890 egilent. Mass spectra were obtained with a Massens 2.3. Synthesis of Polyoxometalate Catalysts
POEKTRO METER CH-7A VARIAN MAT BREMEN spec- 2.3.1. Synthesis of (TBA) [W O ]
2
6
19
trometer.
This catalyst was prepared according to the literature. [21]
A
mixture of sodium tungestate dihydate (Na2WO4.2H2O,99%)
(
100 mmol, 33g), acetic anhydride (40 ml), and DMF (30 ml)
2
.2. General Procedure for the Prepration of Pyridine
◦
was heated at 100 C for 3 hours to obtain a white cream. Then
a solution of acetic anhydride (20 ml) and HCl (18 ml, 12N) in
N-oxides
A mixture of pyridine derivative (5 mmol), aqueous hydro- DMF (50 ml) was added with stirring, and the resulting mixture
gen peroxide 15% (7.5 ml), and appropriate catalyst (0.05 mmol) is filtered off to eliminate the undissolved white solid. A solution
◦
was heated under solvent free conditions at 90 C or in different of tetrabutylammonium bromide (47 mmol, 15 g) in methanol
solvents at reflux temperature.The reaction was monitored by (50 ml) was added with rapid stirring to give a white precipitate.
TLC. After completion of the reaction, the precipitate was fil- This suspension is stirred for 5 min and the product is filtered.
tered off, washed with water and diethyl ether, and air dried to Recrystalyzation from a minimum amount of hot DMSO gives
give pure pyridine N-oxides (Table 1).
colorless diamond-shaped crystals.

914
N. TAVAKOLI-HOSEINI ET AL.
2.3.2. Synthesis of H14[NaP5W30O110]
the pyridine nitrogen, causing, to some extent, a repulsion be-
H14[NaP5W30O110] was prepared by passage of a solution of tween the identical negative charges, resulting in the planar car-
the potassium salt[ in water through a column (50 cm × 1 cm) boxylate anion being in a perpendicular position with respect
22]
of Dowex 50w × 8 in the H+ form and evaporation of the elute to the pyridine ring, which is therefore subjected to a better
to dryness under vacuum.
carboxylate anion elimination. Pyridine-2- carboxylic acid af-
forded the pyridine N-oxide exclusively, with excellent yield and
100% selectivity. Also N-oxidation of pyridine-3-carboxylic
acid and pyridine-2,3-dicarboxylic acid proceeded with good
yields. An interesting observation in our system was high yield
of 2- pyridine N-oxide in oxidation of pyridine-2-carboxylic
acid. To establish the generality of method, we selected three
other pyridines with amino, methyl and bromo moities. The
catalytic oxidation of these pyridines have examined in the
presence of both Preyssler salts catalyst and tetrabutylammo-
nium hexatungestate isopolyanion. The results are presented
in Table 1. These results show good to excellent activity for
them.
2.3.3. Synthesis of catalysts 1 and 2
To a stirred aqueous solution of H14[NaP5W30O110].25.5
H2O was added a solution of THABr or THPABr dropwise
molar ratio: 1:14). The mixture was stirred for about 6h, which
(
led the formation of an viscous solid and an oil for THA and
THPA, respectively. The separated compounds were purified in
a mixture of water and acetonitrile. Recrystalization was per-
formed in water and acetonitrile. The number of THA and THPA
[23]
cations were determined via TG analysis.
3.
RESULTS AND DISCUSSION
The catalytic oxidation of tertiary amines to the correspond-
3.2. Effect of the Reaction Time
ing N-oxides by organic salts of polyoxometalate catalysts and
hydrogen peroxide as oxidant was carried out in three differ-
ent solvents at reflux and under solvent free conditions at 90 C.
For all substrates in the presence of three solvents and under
◦
solvent free conditions, the effect of reaction times on yield of
pyridine N-oxides was studied (Table 1). The results showed
that for 3, the maximum of yield can be obtained after one hour
under solvent free conditions, while for 1 and 2 the maximum
of yields can be obtained after 4–6 hours.
Acetonitrile, toluene, and tetrahydrofuran were examined as sol-
vents. Among these solvents, tetrahydrofuran was the solvent of
choice for reactions catalyzed by 1 and 2. Water miscible sol-
vents like methanol and ethanol were poor solvents at room and
reflux temperatures in the presence of organic salts of 1 and 2.
For 3, solvent free conditions were excellent toward the organic
solvents. One of the important factors affecting the behavior of
POMs is the energy gap between the highest occupied molecular
orbital (HOMO) and the lowest unoccupied molecular orbital
3.3. Effect of the Catalyst Type
All of these three catalysts are the strongly crystalline ma-
terials that are soluble in most of organic solvents, such as
acetonitrile, CH2Cl2, and THF, and all of them are stable to air
and moisture. As we can see in Table 1, tetrabutylammonium
hexatungestate 3 shows the best catalytic activity.
The good performance of catalytic activity of 3 can be
attributed to the double role of it as solvent and catalyst,
so it can affect not only the yield, but also acceleration of
reaction.
(LUMO). The POMs are easily reducible chemical species, and
thus the energy of the LUMO must be sufficiently low to ac-
cept the incoming electron in catalytic reactions. The solvent
molecules stabilize POMs and place these molecular orbitals at
the appropriate level. The effects of COOH position, catalyst
type and reaction time have been studied.
3
.1. Effect of Position of the COOH Group
The effect of the COOH position in oxidation of pyridine car-
4.
CONCLUSION
In summary, the present study demonstrates the catalytic
boxylic acids has been examined in the presence of organic salts
of polyoxometalates catalysts. Our studies showed that for prod-
uct type, the position of COOH group with respect to nitrogen
is a very important factor. In general, the observed selectivity
was 100%. Interestingly, the GC-mass results, mass and melt-
ing points of pyridine N-oxides showed, pyridine-2-carboxylic
acid, and pyridine-2,3-dicarboxylic acid can be oxidized along
with decarboxylation to give decarboxylated pyridine N-oxides,
while pyridine-3-carboxylic acid is oxidized to the related
N-oxide without any decarboxylation. The higher efficiency
for decarboxylation in 2-position with respect to nitrogen for
pyridine-2-carboxylic acid, and pyridine- 2,3-dicarboxylic acid
can, most probably, be explained in the following way: the car-
boxylate anion forming in the transition state is very close to
activity of some organic salts of polyoxometalates such as
(THA)7.7H6.3[NaP5W30O110], (THPA)7.5 H6.5[NaP5W30O110],
and (TBA)2[W6O19] in N-oxidations of pyridine derivatives.
The significance of this study with inexpensive and easily pre-
pared catalysts fundamentally lies in the fact that their use
would lead to an alternative technology for the other system
and amines, which are of interest for the pharmaceutical indus-
try and nanotechnology, with advantages from the point of view
of the environmental care.
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