Silica-supported molybdic acid: Preparation, characterization, and its catalytic application in synthesis of pyranocoumarins

Article abstract of DOI:10.1007/s00706-015-1551-3

Silica-supported molybdic acid was employed as novel, recyclable, and safe catalyst in a one-pot threecomponent condensation of aldehydes, malononitrile, and 4-hydroxycoumarin to produce new and known pyr- ano[2,3-c]chromenes as potent biologically active

Full text of DOI:10.1007/s00706-015-1551-3

Monatsh Chem
DOI 10.1007/s00706-015-1551-3
ORIGINAL PAPER
Silica-supported molybdic acid: preparation, characterization,
and its catalytic application in synthesis of pyranocoumarins
Bahador Karami1 Mahtab Kiani1
•
Received: 2 May 2015 / Accepted: 3 August 2015
Ó Springer-Verlag Wien 2015
Abstract Silica-supported molybdic acid was employed
as novel, recyclable, and safe catalyst in a one-pot three-
component condensation of aldehydes, malononitrile, and
4-hydroxycoumarin to produce new and known pyr-
ano[2,3-c]chromenes as potent biologically active
compounds. This expedient new route has advantages, such
as the use of a safe and reusable catalyst, simple operation,
short reaction times, and good to excellent yields. The
silica-supported molybdic acid as a novel solid acid was
characterized by X-ray fluorescence, X-ray diffraction, and
Fourier transform infrared spectroscopy.
Introduction
Multicomponent reactions are one of the most interesting
concepts in modern synthetic chemistry [1]. Multicom-
ponent reactions (MCRs), defined as one-pot reactions in
which at least three different substrates join through
covalent bonds, have steadily gained importance in syn-
thetic organic chemistry. MCRs allow the creation of
several bonds in a single operation and offer remarkable
advantages like convergence, operational simplicity, facile
automation, reduction in the number of work-up, extrac-
tion, and purification processes, and hence minimize
waste generation, rendering the transformations green [2].
Development of MCRs can lead to new efficient synthetic
methodologies to afford many small organic compounds
in the field of modern organic, bioorganic, and medicinal
chemistry [3]. Hence, MCRs are considered as a pivotal
theme in the synthesis of many important heterocyclic
compounds such as chromene derivatives nowadays [4].
Pyrano[3,2-c]chromene is a class of vital heterocycles
with a wide range of biological effects such as spas-
molytic, diuretic, anticoagulant, anticancer, and anti-
anaphylactic activity [5]. Compounds having dihydropy-
ran structural motif exhibit a wide range of biological
activities, such as diuretic, analgesic, myorelaxant activity
[6], anticoagulant [7], anticancer [8], anti-tumoral [9], and
anti-HIV [10]. In addition, they are also useful for the
treatment of neurodegenerative disorders including Alz-
heimer’s disease, amyotrophic lateral sclerosis,
Huntington’s disease, and Parkinson’s disease [11].
Moreover, they are also used as cosmetics, pigments [12],
and useful as photoactive materials [13]. A considerable
effort has been made for the synthesis of pyran-annulated
heterocyclic derivatives due to their wide applications
[14].
Graphical abstract
Keywords Silica-supported molybdic acid Á
Recyclable catalyst Á Pyrano[2,3-c]chromenes Á
X-ray fluorescence Á X-ray diffraction
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-015-1551-3) contains supplementary
material, which is available to authorized users.
& Bahador Karami
karami@mail.yu.ac.ir
1
Department of Chemistry, Yasouj University, P. O. Box 353,
Yasouj 75918-74831, Iran
123

B. Karami, M. Kiani
Scheme 1
ONa
O Mo O
O
OH
OH
O Mo O
O
Si
O
O
O
SOCl2
Si
O
Si
O
O
SiO2
Reflux
48 h
-SO2
- HCl
O
O
O
HCl/ H2O, 1 h
-NaCl
Cl
SiO2
Si
O
SiO2
O
O
Na2MoO4
pH = 6.26
2
SiO2
n-Hexane
Reflux, 4 h
pH = 4.36
-NaCl
1
A literature survey shows that several modified meth-
ods have been reported using different homogeneous or
heterogeneous catalysts such as cetyltrimethylammonium
chloride/bromide [15, 16], tetrabutylammonium bromide
(TBAB) [17], triethylbenzylammonium chloride (TEBA)
[18], chitosan [19], K3PO4 [20], Na2CO3 under grinding
[21], Mg/Al hydrotalcite [22], [BMIm]BF4 [23], [2-
aemim][PF6] [24], DBU [25], and piperidine under
microwave irradiation [26]. However, many proposed
methods for the synthesis of these compounds suffer from
disadvantages including relying on multi-step conditions,
the use of toxic organic solvents or catalysts containing
transition metals, tedious work-up procedure, troublesome
waste discarding, high reaction time, and low yields [27].
Thus, obviation of these limitations is necessary to
develop a simple and green synthesis of 2-amino-4H-
chromenes.
Table 1 XRF data of SSMA 2
Compounds
Concentration/%
SiO2
MoO4
Na2O
Cl
71.14
25.62
1.90
0.460
0.355
0.289
0.046
0.045
0.027
0.023
0.022
0.022
99.95
ZnO
CaO
Fe2O3
Al2O3
CuO
GeO2
MnO
TiO2
Total
In this work, a new methodology to obtain novel and
known pyrano[2,3-c]chromenes, via a one-pot three-com-
ponent condensation, is reported. In this paper, we
introduce silica-supported molybdic acid (SSMA) as a
novel and safe catalyst for the synthesis of novel and
known pyranocoumarin derivatives.
synthetic point of view, the nucleophilic substitution at
silicon is also attractive.
SSMA was characterized by X-ray fluorescence (XRF),
X-ray diffraction (XRD), and FT-IR spectra. As can be
seen in Table 1, XRF data for the SSMA show the com-
position of the catalyst as 71.14 (%W/W) SiO2 and 25.62
(%W/W) MoO4.
Figure 1 shows the XRD patterns for the silica molybdic
acid which exhibits the presence of molybdic acid crys-
talline phase supported on amorphous silica as a broad
peak around 23° (2h). The three peaks in the 35–40° region
of the XRD spectrum could be attributed to the presence
and linking of MoO3 to the silicagel [33].
Results and discussion
In continuation of our previous studies on the development
of various catalysts in synthesis of organic compounds [29–
31], as can be seen in Scheme 1, from the reaction of
readily available materials such as silicagel and thionyl
chloride, silica chloride 1 has been prepared [32].
Accordingly, we found that anhydrous sodium molybdate
can react with 1 to give silica-supported molybdic acid
(SSMA, 2). This reaction is clean and easy. From the
The FT-IR spectra for the anhydrous sodium molybdate,
silica chloride, and silica-supported molybdic acid are
shown in Fig. 2. This spectrum shows the characteristic
bonds of anhydrous sodium molybdate and silica chloride.
123

Silica-supported molybdic acid: preparation, characterization, and its catalytic application…
Fig. 1 XRD pattern for the SSMA (2)
The adsorption in 3452, 1634, 1086, 800 cm-1 in the
catalyst spectrum reveals both bonds in SiO2–Cl and MoO4
groups.
In continuation of our efforts toward the development of
novel, efficient, and green procedures for the synthesis of
organic compounds [34–36] using safe catalysts [37–39],
we turned our attention toward the three-component con-
densation of malononitrile (3), aromatic aldehydes 4, and
4-hydroxycoumarin (5) to produce pyrano[2,3-c]coumarins
6 in the presence of SSMA (Scheme 2).
The successful incorporation of molybdate groups was
also confirmed by EDX analysis (Fig. 3), which showed
the presence of Mo in addition to Si and O elements.
We evaluated the amounts of molybdic acid supported on
SiO2 using two methods, including (a) titration with 0.1 N
NaOH (neutralization reaction) and (b) calculating the
weight difference between primary solid acid loosed chlo-
ride and new silica-supported molybdic acid. After these
experiments, we found that 1 g catalyst includes 0.04 g –
OMoO3H. Regarding to the molecular weight of MoO4H
(161 g), therefore, 1 g of catalyst is equal to 0.25 mmol.
In order to optimize the reaction conditions, we used
both protic and aprotic solvents in the presence of various
amounts of the SSMA in the reaction of benzaldehyde, 3,
and 5 as a model to investigate the effects of the solvent
and the catalyst for preparing compounds 6a. In this case,
the substrates were mixed together in 10 cm3 of the
solvent.
123

B. Karami, M. Kiani
Fig. 2 FT-IR spectra for the
comparison of SiO2Cl,
Na2MoO4, SSMA, and recycled
SSMA
Fig. 3 Energy dispersive
spectroscopy (EDAX) pattern of
SSMA
As shown in Table 2, we found that polar and protic
solvents, such as H2O and EtOH or MeOH, afford better
yields than aprotic ones and also an equal mixture of H2O
and EtOH is the most effective solvent. The effect of
temperature was also studied for this reaction and it was
found that the reaction would be completed after 360 min
at room temperature. However, the thermal-assisted model
reaction is efficiently carried out by adding catalytic
amounts of SSMA (5 mol%) in a mixture of EtOH and
H2O (50/50).
After optimization of the reaction conditions, in order to
extend the scope of this reaction, a wide range of aromatic
123

Silica-supported molybdic acid: preparation, characterization, and its catalytic application…
Scheme 2
Table 2 Effect of solvent and catalyst on the synthesis of 6a under
refluxing conditions (90 °C); reaction time 40 min
Table 3 Synthesis of pyrano[2,3-c]coumarin derivatives using
SSMA
Entry
Catalyst/mol%
Solvent
Yield/%
Entry Ar
Time/min Yielda/% M.p./°C
1
2
3
4
5
6
7
8
9
10
5
5
CH2Cl2
55
6a
6b
6c
6d
6e
6f
C6H5
40
25
35
40
80
70
55
80
25
35
94
90
80
75
70
83
89
75
87
93
88
90
94
86
260–262 [40]
232–234 [40]
260–262 [40]
263–265 [40]
232–233 [40]
254–256 [40]
263–265 [40]
263–265 [40]
274–276 [41]
287–289 [37]
275–277 [37]
266–268 [42]
243–245
CH3Cl
60
4-MeO–C6H4
2-Cl–C6H4
5
EtOH
80
5
MeOH
83
3-NO2–C6H4
4-NO2–C6H4
4-Me–C6H4
4-Cl–C6H4
5
H2O
67
–
H2O/EtOH
H2O/EtOH
H2O/EtOH
H2O/EtOH
H2O/EtOH
Trace
65
1
6g
6h
6i
3
89
2-Thienyl
5
94
3-Br–C6H4
10
90
6j
2-Cl–6-F-C6H3
6k
6l
4-Benzyloxy-C6H4 50
1-Naphthyl
90
45
25
aldehydes were used with 3 and 5 (Table 3). All the
products were characterized by comparison of their spectra
and physical data with those reported in the literature [37,
40–42].
6m
6n
a
4-Isopropyl-C6H4
Cyclohexyl
267–270
Isolated yield
Table 4 demonstrates the merit of this method for the
synthesis of pyrano[2,3-c]coumarins in comparison with
previously reported results. As it can be seen from Table 4,
piperidine was employed as a basic catalyst under refluxing
EtOH, but this method could not afford good yields (entry
1). In the case of (S)-proline (entry 4), the product was
obtained in low yield in a long time. In other variations,
such as DAHP (entry 3), KF-Al2O3 (entry 5), and TEBA
(entry 6), the methods need too long reaction times. We
believe that these reactions can be efficiently carried out
under our suggested conditions with respect to reaction
times and product yield.
arylmethylene via a Knoevenagel condensation of the
aldehyde and malononitrile catalyzed by SSMA 2. In the
next steps, a Michael-type addition to the arylmethylene
and subsequent heterocyclization promoted by SSMA give
the corresponding products 6.
The main disadvantage of many reported methods for
these reactions is that the catalysts are destroyed in the
work-up procedure and cannot be recovered or reused. In
these processes, as outlined in Fig. 4, the SSMA showed
recyclability up to six runs without any considerable loss in
the product yield and its catalytic activity. The FT-IR
spectra of the catalyst after six runs (Fig. 2) showed the
same spectral fingerprint of the freshly prepared catalyst
indicating the stability of the catalyst throughout the
recycling experiment.
A mechanistic rationale for the formation of pyra-
nocoumarins 6 is suggested in Scheme 3. It seems that the
reaction takes place in three steps. It is reasonable to
assume that the initial event involves the generation of the
123

B. Karami, M. Kiani
Table 4 Comparison of present work with other methods reported in the literature
Entry
Conditions
Time/
min
Yield/
%
1
2
3
4
5
6
7
Piperidine (0.5 cm3), EtOH, reflux
SDS (20 mol%), H2O, 60 °C
DAHP (10 mol%), H2O:EtOH (1:1), r.t.
(S)-Proline (10 mol%), H2O:EtOH (1:1), reflux
KF-Al2O3 (0.125 g), EtOH, reflux
TEBA (0.07 g), H2O, 90 °C
30
120
180
240
240
420
40
70 [43]
85 [44]
81 [45]
72 [45]
90 [46]
96 [18]
94a
SSMA (5 mol%), H2O:EtOH (1:1), reflux
Synthesis of 6a
a
Present work
Scheme 3
O
Si O Mo O
O
OH
O
+
H
H
Ar
O
Si O Mo O
O
H
NC
CN
Ar
H
3
4
N
H
O
HO
N
O Mo OH
O
Ar
NH2
CN
Ar
O
O
N
N
O
6
Ar
O H
O
NH2
HN
O
O
C
CN
Ar
CN
H
Ar
O
O
O
O
O
O
5
H
O
O
O
O
O
O
O
O
O Mo OH
O
123

Silica-supported molybdic acid: preparation, characterization, and its catalytic application…
Finally, the mixture was filtered, washed with distilled
water, and dried to afford SSMA.
Preparation of pyrano[2,3-c]coumarin derivatives 5
using SSMA
Malononitrile (3, 1.1 mmol), aromatic aldehyde
4
(1 mmol), 4-hydroxycoumarin (5, 1 mmol), and SSMA (2,
5 mol%) were added to a 10-cm3 mixture EtOH/H2O (50/
50) in a 25-cm3 Pyrex flask and refluxed for an appropriate
time (Table 3). The reaction progress was controlled by
thin layer chromatography (TLC) using hexane/EtOAc
(1:1). After completion of the reaction, the solvent was
removed under vacuum, the crude products 6 were
obtained after recrystallization from EtOH.
Fig. 4 Recyclability of SSMA for synthesis of 6a. Reaction time
40 min
2-Amino-4-(4-isopropylphenyl)-3-cyano-4H,5H-pyr-
ano[3,2-c]chromene-5-one (6m, C22H18N2O3)
IR (KBr): v = 3389, 3310, 2201, 1713, 1671, 1606, 1374,
Experimental
The chemicals were purchased from Merck and Aldrich
chemical companies. The silica chloride 1 was synthesized
according to the published procedure [28]. The reactions
were monitored by TLC (silicagel 60 F254, hexane :
EtOAc). Fourier transform infrared (FT-IR) spectroscopy
spectra were recorded on a Shimadzu-470 spectrometer,
using KBr pellets and the melting points were determined
on a KRUSS model instrument. 1H NMR spectra were
recorded on a Bruker Avance II 400 NMR spectrometer at
400 MHz, in which DMSO-d6 was used as solvent and
TMS as the internal standard. X-ray diffraction (XRD)
pattern was obtained by Philips X Pert Pro X diffrac-
tometer operated with a Ni filtered Cu Ka radiation source.
X-ray fluorescence (XRF) spectroscopy was recorded by
X-Ray Fluorescence Analyzer, Bruker, S4 Pioneer, Ger-
many. The varioEl CHNS Isfahan Industrial University
was used for elemental analysis.
1049 cm-1 1H NMR (DMSO-d6, 400 MHz): d = 7.90
;
(dd, J = 6.5, 1.3 Hz, 1H), 7.73–7.69 (m, 1H), 7.51–7.44
(m, 2H), 7.38 (s, 2H), 7.19–7.15 (m, 4H), 4.41 (s, 1H), 2.84
(m, 1H), 1.17 (d, J = 6.9 Hz, 6H) ppm; 13C NMR (DMSO-
d6, 100 MHz): d = 159.54, 158.00, 157.95, 153.28,
152.08, 147.11, 140.70, 132.88, 127.45, 126.42, 124.65,
122.41, 119.29, 116.54, 112.95, 104.18, 58.03, 38.85,
36.50, 33.23, 23.79 ppm.
2-Amino-4-cyclohexyl-3-cyano-4H,5H-pyrano[3,2-c]chro-
mene-5-one (6n, C19H18N2O3)
IR (KBr): v = 3427, 3280, 2188, 1720, 1669, 1594, 1389,
;
1048 cm-1 1H NMR (DMSO-d6, 400 MHz): d = 7.82
(dd, J = 6.4, 1.4 Hz, 1H), 7.72–7.67 (m, 1H), 7.48–7.43
(m, 2H), 7.35 (s, 2H), 4.43 (s, 1H), 1.74 (m, 1H), 1.63–1.57
(m, 4H), 1.38–1.32 (m, 2H), 1.18–0.94 (m, 4H) ppm; 13C
NMR (DMSO-d6, 100 MHz): d = 160.64, 160.06, 154.63,
152.02, 132.67, 124.56, 122.05, 116.53, 116.00, 113.00,
104.60, 52.48, 43.18, 36.66, 30.51, 27.52, 26.11, 25.85,
25.52 ppm.
Preparation of silica chloride 1
To an oven-dried (125 °C, vacuum) sample of silicagel 60
(10 g) in a round bottomed flask (250 cm3) equipped with a
condenser and a drying tube, thionyl chloride (40 cm3) was
added and the mixture in the presence of CaCl2 as a drying
agent was refluxed for 48 h. The resulting white-grayish
powder was filtered and stored in a tightly capped bottle [28].
Acknowledgments We thank the Yasouj University for their
support.
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