Application of silica vanadic acid [SiO2-VO(OH)2] as a heterogeneous and recyclable catalyst for oxidative aromatization of Hantzsch 1,4-dihydropyridines at room temperature

Article abstract of DOI:10.1007/s13738-014-0431-9

A simple method for the oxidative aromatization of Hantzsch 1,4-dihydropyridines to the corresponding pyridines is described using hydrogen peroxide as green oxidant and silica vanadic acid as catalyst in acetonitrile at room temperature. The catalyst can

Full text of DOI:10.1007/s13738-014-0431-9

J IRAN CHEM SOC
DOI 10.1007/s13738-014-0431-9
ORIGINAL PAPER
Application of silica vanadic acid [SiO2-VO(OH)2]
as a heterogeneous and recyclable catalyst for oxidative
aromatization of Hantzsch 1,4-dihydropyridines at room
temperature
•
Maliheh Safaiee Mohammad Ali Zolfigol
•
•
Mahsa Tavasoli Mohammad Mokhlesi
Received: 30 August 2013 / Accepted: 7 February 2014
Ó Iranian Chemical Society 2014
Abstract A simple method for the oxidative aromatiza-
tion of Hantzsch 1,4-dihydropyridines to the corresponding
pyridines is described using hydrogen peroxide as green
oxidant and silica vanadic acid as catalyst in acetonitrile at
room temperature. The catalyst can be easily recovered and
reused for 15 reaction cycles without considerable loss of
activity.
useful examples of support materials is silica gel. This
inorganic supporter has some advantageous properties
such as excellent stability, good accessibility and high
surface area; this will be beneficial to the enhancement of
loading amount and dispersion of catalytic action [1].
Also, the design of silica-supported transition metal
oxides represents a rapidly growing field that has been
significantly applied in industry. Among the various
transition metals, vanadium, an early member of the 3d
transition metal series, exists on the surface of the earth
more abundantly and catalytic systems based on the
supported vanadium oxide exhibit interesting catalytic
properties for the partial oxidation of alkanes, aromatics,
alcohols, and alkenes and dehydrogenation of different
hydrocarbons [2–4].
Keywords Hantzsch 1,4-dihydropyridines Á
Aromatization Á Hydrogen peroxide Á Silica vanadic acid
Introduction
Development of heterogeneous catalysts for fine chemi-
cals synthesis has become a major area of research. One
of the major drawbacks of the homogeneous catalysts is
the difficulty in separating the relatively expensive cat-
alysts from the reaction mixture at the end of the process.
The possible contamination of catalyst in the product also
restricts their use in industry. Efficient anchoring of these
catalysts on supports may overcome these drawbacks.
Since the catalytic action occurs at specific sites on the
solid surface, often called ‘‘active sites’’, the uniform
dispersion of metal catalysts is highly desirable for sig-
nificant improvement of catalytic action. These types of
catalysts have used various support materials. One of the
Hantzsch 1,4-dihydropyridines are easily prepared from
the Hantzsch reaction or its modifications [5–8]. In recent
years, it has been found that drugs such as nifedipine and
niguldipine undergo redox processes due to the catalysis of
cytochrome P-450 in the liver during their metabolism [9].
Therefore, the oxidation of 1,4-dihydropyridines has
attracted considerable attention. Several oxidation reagents
have been reported for the oxidation of 1,4-dihydropyri-
dines, such as SeO2 [10], lead(IV) tetraacetate [11], FeCl3/
KMnO4 [12], Pd/C [13], nicotinium dichromate [14], sil-
ica-gel-supported ferric nitrate (silfen), N2O3, MClx/
NaNO2/wet SiO2 and silica chloride/NaNO2 wet SiO2 [15,
16], H2O2/Co(OAc)2 [17], NaHSO4/Na2Cr2O7/wet SiO2
[18], peroxydisulfate-cobalt(II) [19], Zr(NO3)4 [20],
Co(II)-catalyzed auto oxidation) [21], KBrO3/MCln [22,
23], (n-Bu)4IO4/[Mn(TPP)Cl] [24], Mn(III)-salophen/
NaIO4 [25], oxone [26], M(NO3)2.XH2O [27], NaClO2
[28], graphite oxide [29], and Solid acid/NaNO2 [30]. In
this paper, we want to apply silica vanadic acid in the
oxidation of dihydropyridines.
M. Safaiee (&)
Department of Aromatic and Medicinal Plants, Nahavand
University, P.O. Box 6591678546, Nahavand, Iran
e-mail: azalia_s@yahoo.com; msafaiee@basu.ac.ir
M. A. Zolfigol Á M. Tavasoli Á M. Mokhlesi
Faculty of Chemistry, Bu-Ali Sina University,
P.O. Box 6517838683, Hamedan, Iran
123

J IRAN CHEM SOC
Scheme 1 Synthesis of silica
vanadic acid (SVA)
O
V
Cl
O V O
Cl
OH
n-Hexane
air
SiO2
SiO2
OH
+
SiO2
O V O
OH
r.t
Cl
Cl
Cl
(I)
(II)
Silica Vanadic Acid (III)
Table 1 Oxidation of various dihydropyridines under mild
conditions
Experimental
Entry R1
R2
Substrate Product Time Yield
(min) (%)
Synthesis of silica vanadic acid
1
2
3
4
5
6
COMe
H
COMe Me
COMe Ph
1a
1b
1c
2a
2b
2c
2d
2e
2f
10
18
60
26
25
53
97
95
50
95
98
88
In a 100 mL round-bottomed flask, n-hexane (25 mL) and
silica gel (4.0 g) were stirred for 10 min and then vanadi-
umoxytrichloride (4.0 g) was dissolved in n-hexane
(25 mL) and added drop wise to the silica gel suspension
(15–20 min). After addition of VOCl3, the red-brown
mixture was stirred for 10 h. Then, solvent was evaporated
and the residue (the red-brown powder (II) was obtained
after the grafting process) was filtered, washed with dry n-
hexane several times to remove unreacted VOCl3, dried
under vacuum, and stirred in the air for 72 h to promote the
hydrolysis of V–O–Cl bonds. At this time the red-brown
powder changed to dark green powder (III) slowly
(Scheme 1) [31, 32]. Typical loading of vanadium was
determined using X-ray fluorescence (XRF) and showed a
loading 8 0.1 mmol g–1.
COMe 2-OMe–C6H4 1d
COMe 4-OMe–C6H4 1e
COMe 2,5-(OMe)2– 1f
C6H3
7
COMe 2-NO2–C6H4 1 g
COMe 3-NO2–C6H4 1 h
2 g
2 h
2i
55
35
26
10
13
45
16
18
90
9
65
93
93
95
90
90
90
92
90
94
93
96
8
9
COMe 2-Furyl
COOEt
1i
10
11
12
13
14
15
16
17
18
H
1j
2j
COOEt Me
COOEt Et
1 k
1 l
2 k
2 l
2 m
2n
2o
2p
2q
2r
COOEt 2-OMe–C6H4 1 m
COOEt 3-NO2–C6H4 1n
COOEt 2-Pyridyl
COOEt 3-Br–C6H4
COOEt 4-Br–C6H4
COOEt 2-Furyl
1o
1p
1q
1r
General procedure for the oxidation of 1,4-
dihydropyridines
14
20
A suspension of compound 1, silica vanadic acid, and H2O2
(5 mmol) in CH3CN (5 mL) was stirred at room temperature
for a specific time (molar ratio of reagents and reactions
times are indicated in Table 1). The progress of the reaction
was monitored by thin-layer chromatography (TLC). After
the spot of starting material 1 on TLC disappeared (Scheme
2), the reaction mixture was filtered off. The solvent was
removed, and pure product 2 was obtained.
Reaction condition: dihydropyridines (1 mmol), H2O2 (30 %)
(5 mmol), SVA (0.01 g), CH3CN (5 mL), room temperature, stir
Table 2 Oxidation of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyri-
dinedicarboxylate using in various amount of catalyst
Entry
Oxidant (mmol)
Catalyst
Time (min)
Yield (%)a
1
2
3
4
5
5
5
5
–
5
0.01
0.05
0.1
10
10
95
95
95
60b
95
10
Results and discussion
0.05
–
100
330
In continuation of our studies on the synthesis of new
inorganic silica-based resins [33], we found that silica gel
reacts with vanadiumoxytrichloride to give silica vanadic
acid.
Reaction condition: 1,4-dihydro pyridine (1 mmol), CH3CN (5 mL),
stir, room temperature
a
Isolated yield
b
Conversion
Based on our previous studies on the use of silica
vanadic acid as catalyst for carrying out organic reactions
[31, 32], and continuing our interest in aromatization of
Hantzsch 1,4-dihydropyridines [34], we examined the
possibility of using a silica vanadic acid as a oxidation
agent in the presence of H2O2 on the oxidation aromati-
zation of Hantzsch 1,4-dihydropyridines.
A good range of dihydropyridines(1) was subjected to
the oxidation reaction in the presence of silica vanadic acid
and H2O2, in acetonitrile (Scheme 2).
We preferred hydrogen peroxide as oxidant over other
available oxidizing agent since it is cheap, operationally
safe, environmentally friendly and easy to handle while it
123

J IRAN CHEM SOC
Scheme 2 Oxidation of 1,4-
DHP using SVA/H2O2 in
acetonitrile at room temperature
R2
N
R2
H
OH
O V O
OH
R1
R1
R1
R1
SiO2
CH3
H3C
N
H
CH3
CH3CN/ H2O2
H3C
1
2
R1= CO2Et , COMe
R2= Alkyl , Aryl, Phenyl, Heteroaromatic
substituents at C-4. The reaction is quite general and is
successfully applied to 1,4-DHPs having aliphatic as well
as, substituents at C-4.
Table 3 Optimization of solvent for SVA–H2O2 mediated oxidative
aromatization of 3,5-diacetyl-1,4-dihydro-2,6-dimethylpyridine
Entry
Solvent
Time
Yieldb
The reaction was mild and the workup was straightfor-
ward, requiring simple evaporation of the solvent; then,
highly pure pyridine derivatives 2 could be obtained if the
product is passed through a short pad of silica gel and
evaporation of the solvent. The results and reaction con-
ditions are given in Table 1.
1
2
3
4
5
6
7
8
CH3CH2OH
CH3OH
70
55
60
95
95
95
95
40
93
97
CHCl3
41
CH2Cl2
35
CH3COOC2H5
H2O
53
100
75
In order to recover the catalyst, CH3CN was evaporated
under reduced pressure and removing the product by
extracting with ether from the reaction mixture and
charging the reaction vessel with fresh substrate and H2O2
30 % and then repeating the experiment. The recovered
catalyst was reused fifteen times in the oxidation of 3,5-
diacetyl-1,4-dihydro-2,6-dimethylpyridine (1a) with H2O2,
and smooth loss of catalytic activity was observed from the
11th time of reuse (Table 4).
n-Hexane
CH3CN
10
Reaction condition: 1,4-dihydropyridine (1 mmol), silica vanadic acid
(0.01 g), H2O2 (5 mmol), stir, rt
b
Isolated yield
produces only water as a by-product, which reduces puri-
fication requirements.
To assess the capability and efficiency of our catalyst
with respect to the reported catalysts for oxidation of di-
hydropyridines, the results of the application of these cat-
alysts for the preparation of some pyridines are tabulated in
Table 5. The described method has many advantages over
other methods, such as, high recycling, short reaction time,
high TON and TOF of catalyst.
In order to get the best reaction condition, the effi-
ciency of a variety of silica vanadic acid (SVA) in the
oxidation of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyri-
dinedicarboxylate as a model reaction was studied. The
best catalytic activity was optimized to be 0.01 g for
1 mmol of starting material in the model reaction and
using the catalyst excess (0.05 g) does not show further
increase in the conversion and yield of the product. Also,
in the absence of catalyst or oxidant, the reaction goes
slow or is not complete (Table 2).
A plausible mechanism of these oxidizing systems is
shown in Scheme 3. The catalytic cycle involves, as fun-
damental step, the formation in the active site of a perox-
ovanadium species (III) [31, 32], which is a much stronger
oxidant than H2O2. This is followed by proton transfer
from SVA to generate peroxidic species (V) [38, 39]. The
nitrogen atom of 1,4-DHP attacked peroxidic oxygen(V) to
produce hydroxylammonium ion (VI), then proton transfer
from nitrogen to hydroxy group gives protonated N-
hydroxyl-1,4-dihydropyridine, and finally dehydration and
deprotonation of protonated N-hydroxyl-1,4-dihydropyri-
dine afford the pyridine as depicted in scheme 3 [40].
In conclusion, our goal in undertaking this line of work
was fourfold: (a) to simplify operation due to the hetero-
geneous nature of reaction; (b) to develop a high yielding
Solvent effect on oxidation reaction, in ethanol, meth-
anol, chloroform, ethylacetate, water, n-hexane, acetoni-
trile and dichloromethane was investigated. Although these
organic mediums were found unsuitable for this oxidative
aromatization, SVA/H2O2 system worked quite efficiently
in acetonitrile. The results of this study are summarized in
Table 3.
A series of 1,4-DHPs were aromatized using the opti-
mized reaction conditions (as shown in Table 1). The
reaction proceeded smoothly with various 1,4-DHPs bear-
ing electron rich as well as electron deficient aromatic
123

J IRAN CHEM SOC
Table 4 The catalytic activity of SVA in 15 cycles for the oxidation of 3,5-diacetyl-1,4-dihydro-2,6-dimethylpyridine with hydrogen peroxide
in acetonitrile
Run
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Yield (%)a
Time (min)
97
10
97
10
97
10
97
10
97
10
97
10
97
10
97
10
97
15
97
15
95
15
95
15
95
15
95
15
95
15
a
Isolated yield
Table 5 Comparison of the oxidation of diethyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate to diethyl 2,6-dimethylpyridine-3,5-
dicarboxylate, the reported catalysts versus silica vanadic acid
Entry
Catalyst
Solvent
Time (min)
Yield (%)a
TONd
TOFe (min-1
)
b
1
2
3
4
5
6
a
Silica vanadic acid
Mn(pbdo)2Cl2/MCM-41
Mn(salophenl)/TBAO
Fe(ClO4)3
CH3CN
AcOH
10
90
95 [our work]
c
97 [35]
180.62
–
18.062
–
CH2Cl2
AcOH
30
90 [36]
88 [37]
84 [13]
98 [17]
13.43
44
0.447
0.48
0.04
–
90
Pd/C
AcOH
210
15
8.4
Co(OAc)2
CH3OH
–
No recovery
b
c
d
e
Recovered fifteen times
Recovered three times
Turnover number
Turnover frequency
OH
Scheme 3 The proposed
mechanism of aromatization of
1,4-DHPs
SiO2
V
O
+
H2O2
OH
OH
O
SiO2
V
O
OH
(III)
OH
O
SiO2
V
OH+
OH
(IV)
OH
SiO2
V
O
(V)
O
HO
H
H
H
R2
R2
R2
H2O +H+
N
CH3
R1
H3C
R1
R1
CH3
R1
R1
R1
CH3
R1
R1
CH3
H3C
N
H3C
N
H3C
N
H
R2
H
HO
+
OH2
VI
123

J IRAN CHEM SOC
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