P2O5/SiO2 as an efficient heterogeneous catalyst for the synthesis of heterocyclic alkene derivatives under thermal solvent-free conditions

Article abstract of DOI:10.1039/c3cy00095h

A highly efficient methodology is developed for the synthesis of a series of heterocyclic alkene derivatives 3a-k from 5-chloro-3-methyl-1-phenylpyrazole- 4-carboxaldehyde 1 and active methylene compounds 2a-k, in the presence of P₂O₅

Full text of DOI:10.1039/c3cy00095h

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P2O5/SiO2 as an efficient heterogeneous catalyst for
the synthesis of heterocyclic alkene derivatives under
thermal solvent-free conditions†
Cite this: DOI: 10.1039/c3cy00095h
Zeba N. Siddiqui* and Tabassum Khan
A highly efficient methodology is developed for the synthesis of a series of heterocyclic alkene derivatives
3a–k from 5-chloro-3-methyl-1-phenylpyrazole-4-carboxaldehyde 1 and active methylene compounds
2a–k, in the presence of P2O5/SiO2, under thermal solvent-free conditions, in high yields, within a short
reaction time. The catalyst is characterized for the first time by using X-ray diffraction (XRD), scanning
electron microscopy–energy dispersive X-ray (SEM-EDX) and transmission electron microscopy (TEM). The
stability of the catalyst is evaluated by thermogravimetric analysis/differential thermal analysis (TG/DTA)
and differential scanning calorimetry (DSC) techniques. The molecular structure of alkene 3a is confirmed
by single crystal X-ray diffraction. The advantages of the present methodology are excellent yields of
products, recyclability of the catalyst and an easy operational procedure.
Received 8th February 2013,
Accepted 21st March 2013
DOI: 10.1039/c3cy00095h
www.rsc.org/catalysis
larger surface area and better selectivity, they have become
popular over the last two decades. In addition, silica supported
1. Introduction
Heterogeneous catalysts have received considerable attention in
organic synthesis because of environmental, economical, and
industrial aspects. The use of solid heterogeneous catalysts for
the development of clean processes is a theme of extreme
importance in the chemical industry. These catalysts make the
synthetic process economically viable as they can be easily recov-
ered from the reaction mixture by simple filtration and can be
reused several times to achieve very high turnover numbers
compared to homogeneous catalysts.1 Due to the highly corrosive,
hazardous and polluting nature of liquid acids, the use of solid
acid catalysts because of better regio- and stereoselectivity, low
toxicity and high stability is gaining more importance in the
chemical and refinery industries.2 There are more than 100
industrial processes using over 103 solid acids as catalysts.3
As compared with their homogeneous analogues, immobi-
lization of other catalytically active species on inorganic solid
supports enables generation of recyclable catalysts which show
higher catalytic activities, which may be due to the enhance-
ment of substrate density around the active sites.4 Because of
the higher activity of the silica supported catalysts due to their
reagents are promising for both academic and industrial appli-
cations due to their high mechanical and thermal stabilities,
non-corrosivity and easy separation of the catalyst from the
reaction mixture.5,6
Pyrazole derivatives are an attractive molecular scaffold for
the search of new biologically active molecules. Studies reveal
that incorporation of a pyrazole moiety into various heterocyclic
ring systems gives worthwhile molecules from the biological point
of view.7–9 Several pharmaceutical drugs including celecoxib10 and
rimonabant11 utilize the pyrazole as their core molecular entity.12
Many pyrazole derivatives have a broad spectrum of biological
activities, in particular, 5-chloropyrazole derivatives are reported
to show potential antimicrobial,13 analgesic and anti-inflammatory
activity.14 Moreover, 5-chloro-3-methyl-1-phenylpyrazole-4-
carboxaldehyde, which is used as starting material in the
present study, possesses a halogen and aldehyde function in
an ortho relationship and is a potential candidate for various
organic transformations.15,16
A plethora of chemical methods have been reported for the
formation of CQC bonds, which include Julia olefination,17
Peterson olefination,18 Ramberg–Backlund reaction,19 Wittig
reaction,20 Wadsworth–Emmons reaction,21 Wittig–Horner
Reaction22 and Knoevenagel condensation.23 The Knoevenagel
condensation is a facile and versatile method for the formation
of carbon–carbon double bonds, with numerous applications in
the synthesis of fine chemicals,24 hetero-Diels–Alder reactions25
Department of Chemistry, Aligarh Muslim University, Aligarh, 202002, India.
E-mail: siddiqui_zeba@yahoo.co.in; Tel: + 91 9412653054
† Electronic supplementary information (ESI) available. CCDC 846722. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c3cy00095h
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and in the synthesis of carbocyclic as well as heterocyclic Thermogravimetric/differential thermal analyses (TG/DTA) were
compounds of biological significance.26 The reaction has obtained with a DTG-60H, with a heating rate of 25 1C minÀ1
been utilized in the preparation of coumarin derivatives,27 from 100 to 1000 1C under N2 atmosphere, and the differential
cosmetics,28 perfumes29 and pharmaceutical chemicals.30 The scanning calorimetry (DSC) data obtained with a DSC-60
reaction is usually catalyzed by bases,31 Lewis acids,32 surfac- (Simultaneous DTA-TG Apparatus), Shimadzu (TGA) instru-
tants,33 zeolites,34 amine functionalized MCM-41,35 amino ment with
a 0 to
heating rate of 20 1C minÀ1 from
functionalized mesoporous zirconia,36 ionic liquids37 etc. How- 500 1C under N2 atmosphere. The X-ray single crystal diffrac-
ever, keeping in mind its own intrinsic worth, we decided to tion of compound 3a was performed on a BRUKER AXS SMART
carry out further developments of this procedure in view of APEX diffractometer with a CCD area detector (MoKa = 0.71073 Å,
simplicity and environmentally benign and economic viability, monochromator: graphite).
as many of the reported methods suffer from drawbacks like
complicated preparation of the catalyst, refluxing in hazardous
2.3. Synthesis of the P2O5/SiO2 catalyst
organic solvents for prolonged time, use of expensive and toxic P2O5/SiO2 was prepared by mixing P2O5 (1 mmol, 0.142 g) and
catalysts, high temperature and low product yields, harsh 2 g of dried silica gel 60 (0.125–0.250 mm, previously heated at
conditions with non-recyclable catalysts.
120 1C for 24 h) in a mortar and grinding with a pestle to obtain
In continuation of our earlier studies on the development of a homogenous mixture as a white powder (2.142 g). This
new green protocols,38,39 herein, we report for the first time a reagent is stable and can be kept at room temperature for
P2O5/SiO2 catalyzed synthesis of heterocyclic alkene derivatives months without loss of activity.40
through Knoevenagel condensation under thermal solvent-free
2.4. General procedure for the Knoevenagel reaction
conditions (Scheme 2). In recent years, P2O5/SiO2 has emerged
as a promising heterogeneous solid acid catalyst in many A mixture of 5-chloro-3-methyl-1-phenylpyrazole-4-carboxaldehyde
organic transformations.40–45 The advantages of using this 1 (1.00 mmol), active methylene compounds 2a–k (1.00 mmol)
catalyst are that it is inexpensive, easily preparable, stable, and 2l–n (2.00 mmol), and 0.05g of P2O5/SiO2 (7% w/w)47 were
recyclable, and easily separable from the product.46,47 The mixed thoroughly using a mortar and pestle. The reaction
products are obtained in excellent yields within a short time mixture was then transferred to an open Pyrex 100 mL
period.
beaker and heated at 80 1C for the given time (Table 8). After
completion of the reaction (monitored by TLC), the reaction
mixture was cooled to room temperature and ethyl acetate was
added (5 mL). The reaction mixture was filtered to remove
the catalyst and concentrated to furnish pure products 3a–n
2. Experimental
2.1. Reagents
All starting materials of commercial grade were purchased from (Scheme 2).
Sigma–Aldrich and used without further purification. P2O5
and SiO2 were purchased from Merck. The purity of all com-
3. Results and discussions
3.1. Characterization of the P2O5/SiO2 catalyst
pounds was checked by TLC on glass plates coated with silica
gel (E-Merck G254).
The FT-IR spectrum of P2O5/SiO2 (Fig. 1) showed the stretching
band of SiO–H at 3299–3481 cmÀ1, while the stretching and
2.2. Apparatus and instruments
Melting points were determined on a Riechert Thermover bending bands of P(O)OH appear at 2350, 1634 and 1068 cmÀ1
,
instrument and are uncorrected. The 1H NMR and 13C NMR respectively. The peak at 1230 cmÀ1 was assigned to the
spectra were recorded on Bruker DRX-300 and Bruker Avance stretching of PQO and the peak at 1092 cmÀ1 attributed to
400 spectrometers. TMS was used as an internal standard and Si–O–Si asymmetric band stretching vibrations. The low fre-
chemical shift values were in d (ppm). The microanalytical data quency modes at 794 cmÀ1 were due to the symmetric Si–O–Si
were collected on an Elementar vario EL III elemental analyzer. stretching vibrations.48 The adsorption peak at around 957 cmÀ1
FT-IR spectra were obtained using a Perkin–Elmer spectrometer showed the presence of a Si–O–P bond in the catalyst indicating
and done on KBr disc. The spectra were recorded in the the loading of P2O5 on the SiO2 surface.
400–4000 cmÀ1 wave-number range. Mass spectra were obtained
Formation of the catalytic system (P2O5/SiO2) was identified by
on a Jeol-SX-120 (FAB) and Micromass Quattro II (ESI). X-ray powder XRD (Fig. 2a). The XRD diffraction band at 2y = 171–281
diffractograms (XRD) of the catalyst were recorded in the 2y was found to be broad indicating fine dispersion of P2O5 on the
range of 10–701 (scan rate of 41 minÀ1) on a Rigaku Miniflex silica material and thus confirming the formation of amorphous
X-ray diffractometer with Ni-filtered Cu Ka radiation at a P2O5–silica matrix.49
wavelength of 1.54060 Å. The SEM-EDX analysis was
To study the surface morphology of the catalyst, SEM
obtained using a JEOL JSM-6510 scanning electron microscope micrographs of the catalyst were employed. An examination
equipped with an energy dispersive X-ray spectrometer of SEM images (Fig. 3) showed that P2O5 particles were of
(acc. voltage: 20 kV) at different magnification and transmis- uneven shape and size, well distributed and no conglomeration
sion and an electron microscope (TEM) using JEM-2100 F model of P2O5 particles was found on the surface of the silica gel.
(acc. voltage: 200 kV) with magnification up to 100 000Â. The increased reactivity of P2O5 supported on silica material
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Fig. 1 FT-IR spectra of P2O5/SiO2 catalyst.
Fig. 2 (a) Powder XRD of fresh P2O5/SiO2. (b) Powder XRD of P2O5/SiO2 after five runs.
Fig. 3 SEM images of P2O5/SiO2 catalyst at different magnifications.
could be possibly due to the catalyst–support interactions,
TEM image (Fig. 4) further showed uniform distribution of
and the resultant changes in the surface properties of the P2O5 particles as black dots on the surface of silica, confirming
reactive sites.
the formation of the expected catalyst.
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3.2. Evaluation of catalytic activity of P2O5/SiO2 for the
synthesis of heterocyclic alkene derivatives
In order to optimize the reaction conditions, including tem-
perature, solvents, catalysts, loading of catalyst, and supports in
terms of yield and time, the reaction of 5-chloro-3-methyl-
1-phenylpyrazole-4-carboxaldehyde 1 with 1, 3-dimethyl barbituric
acid 2a was selected as a model reaction.
First the reaction was carried out under grinding at room
temperature without any catalyst. The reaction took longer time
for completion (6 h) with trace amounts of the product being
generated. Then the reactions were conducted at 25, 50, 80 and
100 1C in the presence of P2O5/SiO2 as catalyst (Table 1). The
yield of the product increased from 43% to 99% as the
temperature was raised from 25 to 80 1C. A further increase
in the temperature up to 100 1C did not show any effect.
Therefore, 80 1C was chosen as the optimal temperature for
all further reactions.
To evaluate the efficiency as well as capacity of the solvent-
free conditions in comparison with solvent conditions, the
model reaction was examined in the presence of P2O5/SiO2 in
different solvents such as CH3CN, CH2Cl2, CHCl3, THF, MeOH,
EtOH, H2O and dioxane. When the reaction was performed in
EtOH and MeOH, a moderate yield of the product (3a) was
obtained after a longer time period (Table 2, entry 2, 3) whereas
in the presence of CH3CN, CH2Cl2, CHCl3, H2O, THF and
dioxane, only trace amounts of the product were obtained
(Table 2, entry 4–9). The same reaction was then carried out
using P2O5/SiO2 in solvent-free conditions at room tempera-
ture. The reaction was completed within 1 h, but the yield of the
product was not satisfactory (43%). When the reaction was
performed in solvent-free conditions at 80 1C in the presence of
P2O5/SiO2, it was completed within 2 min with a considerable
increase in the yield of the product (99%) (Table 2). In a
comparative study using other green solvents, the model reac-
tion was also performed in PEG-400 and glycerol and it was
observed that the reaction was completed in relatively shorter
times but with mixture of products (entry 10, 11). Thus,
our study revealed that solvent-free conditions are best for
the P2O5/SiO2 catalyzed synthesis of heterocyclic alkene deriva-
tives in terms of reduced reaction times and excellent yields of
the products.
Fig. 4 TEM image of P2O5/SiO2 catalyst.
Further confirmation for the formation of the expected
catalytic system was done by EDX analysis (Fig. 5) which
showed the presence of Si, O and P elements.
To estimate the thermal stability of P2O5/SiO2, TG/DTA and
DSC experiments were carried out. A weight loss (about 14%)
was observed in the DTA curve (Fig 6a) between 42 1C and
133 1C with an endothermic peak at around 85.55 1C which can
be attributed to the evaporation of residual water molecules.
In the TGA graph (Fig 6a) no apparent weight loss after weight
loss of 14% was observed indicating the stability of the catalyst.
The DSC curve (Fig 6b) showed an irreversible endothermic
transition at 113 1C, which may be due to the loss of adhered
water molecules trapped in silica gel framework.
To the best of our knowledge, there is no report on the
characterization of the catalyst (P2O5/SiO2) using XRD, SEM-
EDX and TEM studies and the stability of the catalyst using
TG/DTA and DSC analysis.
To establish the superiority of P2O5/SiO2 over other hetero-
geneous catalysts, the model reaction was carried out in the
presence of different catalysts. Our investigation revealed that
the catalytic activity of various acidic/basic catalysts in solvent-
free conditions was in the order P2O5/SiO2 > NaHSO4–SiO2
>
Chitosan > NH4OAc–SiO2 > NaHSO4–alumina (acidic) > NaHSO4–
alumina (basic) > NaHSO4–alumina (neutral) in terms of time
and yield. (Table 3). It is thus clear that P2O5/SiO2 (7% w/w)
exhibited the highest catalytic activity with regard to the trans-
formation of heteroaldehyde 1 and active methylene 2a–k into
substituted electrophilic alkenes (3a–k).
In order to prove the efficiency of P2O5/SiO2 for the Knoevenagel
condensation, a comparison with other reported catalysts was
also made (Table 4). In the presence of P2O5/SiO2 the product
Fig. 5 EDX analysis of the fresh catalyst (P2O5/SiO2).
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Fig. 6 (a) TG/DTA graph of P2O5/SiO2. (b) DSC of P2O5/SiO2.
Table 1 Effect of temperature on the synthesis of 3a in thermal solvent-free
products were obtained in varying yields (88–98.2%) and times
(5 min–10 h). It is thus clear from the table that P2O5/SiO2 is
superior to other catalysts in terms of time, yield and reaction
conditions. The work-up procedure is very simple and no
further purification is required for obtaining the pure products.
The higher activity of P2O5/SiO2 as compared to other reported
catalysts may be due to the heterogeneous nature of the
catalyst and the thermal solvent-free conditions. A plausible
mechanism for the Knoevenagel condensation is depicted in
Scheme 1.
conditionsa
Entry
Temperature (1C)
Timeb (min)
Yieldc (%)
1
2
3
4
25
50
80
60
15
2
43
78
99
99
100
2
a
Reaction conditions: 5-chloro-3-methyl-1-phenylpyrazole-4-carboxalde-
hyde (1.0 mmol), 1,3-dimethyl barbituric acid (1.0 mmol), catalyst
0.05 g, T = 80 1C. The reaction work-up was carried out as detailed
b
c
under Section 2. Reaction progress monitored by TLC. All yields
refer to isolated yield.
The activity of different loadings of P2O5 on silica support
was also investigated for the synthesis of 3a by using 3.5, 7 and
10.5% w/w of P2O5 supported on SiO2 (Table 5). With 3.5% w/w
(3a) was obtained in excellent yield (99%) within short times (2 min) P2O5/SiO2 lower yields of the product were obtained in longer
whereas with other reported catalysts Knoevenagel condensation times (Table 5, entry 1) whereas with 10.5% w/w P2O5/SiO2
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Table 2 Effect of various solvents versus solvent-free on the synthesis of 3a in
again the yield was not satisfactory (Table 5, entry 3). An excellent
yield of the product was obtained with 7% w/w P2O5/SiO2
(Table 5, entry 2). The lower activity of 3.5% w/w P2O5 loaded
silica is possibly attributable to the lower ratio of P2O5 to silica
whereas the lower activity of 10.5% w/w P2O5 loaded silica could
be due to multi layer P2O5 on the support.
In evaluating the effect of catalyst concentration, the best
yield was obtained in the presence of 0.05 g P2O5/SiO2.
No significant improvement in the yield was observed on
increasing the loading to 0.075 and 0.1 g, whereas, decreasing
the amount of catalyst to 0.025 g resulted in a lowering of the
a
the presence of P2O5/SiO2
Entry
Solvent
Timeb
Yieldc (%)
1d
2
3
4
5
6
7
8
9
Solvent-free
EtOH
MeOH
CH3CN
CH2Cl2
CH3Cl
H2O
THF
Dioxane
PEG-400
Glycerol
2 min
1.30 h
1.45 h
2 h
2.15 h
4 h
5.10 h
5.18 h
5.25 h
4.16 h
3.44 h
99
60
57
Trace
Trace
Trace
Trace
Trace
Trace
49 (mixture)
10
11
52 (mixture) yield (Table 6).
To establish the use of silica as the best support for P2O5,
other supports were also investigated (Table 7). To evaluate the
role of SiO2, the model reaction was carried out in solvent-free
conditions at 80 1C in the presence of P2O5 alone. We found
that the yield using P2O5/SiO2 was greater (average, 30%) than
for P2O5 alone under the same conditions whereas with acidic,
basic and neutral alumina under similar reaction conditions
a
Reaction conditions: 5-chloro-3-methyl-1-phenylpyrazole-4-carboxalde-
hyde (1.0 mmol), 1,3-dimethyl barbituric acid (1.0 mmol), catalyst 0.05 g,
T = 80 1C. The reaction work-up was carried out as detailed under
b
c
Section 2. Reaction progress monitored by TLC. All yields refer to
isolated yield. Thermal solvent-free conditions.
d
Table 3 Effect of various heterogeneous catalysts on the synthesis of 3a in
thermal solvent-free conditionsa
Entry
Catalyst
Timeb (min)
Yieldc (%)
Table 5 Effect of P2O5 loading on the support for the synthesis of 3a in thermal
1
2
3
4
5
6
7
P2O5/SiO2
NaHSO4–SiO2
Chitosan
NH4OAc–SiO2
NaHSO4–alumina (acidic)
NaHSO4–alumina (basic)
NaHSO4–alumina (neutral)
2
25
33
40
49
65
78
99
80
71
65
54
38
32
solvent-free conditionsa
Entry
P2O5/SiO2 (% w/w)
Timeb (min)
Yieldc (%)
1
2
3
3.5
7
10.5
7
2
2
78
99
82
a
a
Reaction conditions: 5-chloro-3-methyl-1-phenylpyrazole-4-carboxalde-
hyde (1.0 mmol), 1,3-dimethyl barbituric acid (1.0 mmol), catalyst 0.05 g,
T = 80 1C. The reaction work-up was carried out as detailed under
Reaction conditions: 5-chloro-3-methyl-1-phenylpyrazole-4-carboxalde-
hyde (1.0 mmol), 1,3-dimethyl barbituric acid (1.0 mmol), catalyst 0.05 g,
T = 80 1C. The reaction work-up was carried out as detailed under
b
c
b
c
Section 2. Reaction progress monitored by TLC. All yields refer to
isolated yield.
Section 2. Reaction progress monitored by TLC. All yields refer to
isolated yield.
Table 4 Comparison of the results obtained with other reported catalysts for the Knoevenagel condensation products
Entry
Catalyst
Conditions
Time
Yield (%)
Ref.
1
2
3
4
5
6
7
8
P2O5/SiO2
NH4OAc–SiO2
Sulfuric acid–SiO2
Guanidine
L-Proline
Solvent-free/80 1C
Dichloromethane
RT
Dichloromethane
Ethanol
Water
US
Ethanol
Water
2 min
6 h
6 h
99
90
88
97.3
98
91
98.2
95
98
95
Present work
50
51
52
53
54
55
56
57
58
59
60
10 h
40 min
30 min
8 min
5 h
HClO4–SiO2
Potassium sorbate
Amino functionalized mesoporous silica
HAP-g-Fe2O3[Bmim]OH
In/AlMCM-41
NH4OAc
Zn[(L-proline)2]
9
1 h
10
11
12
Ethanol
MW
MW
25 min
5 min
6 min
94
95
Scheme 1 Plausible mechanism for the Knoevenagel condensation.
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Table 6 Effect of catalyst loading on the synthesis of 3a in thermal solvent-free
the yield was moderate to good (Table 7, entry 3–5). It is thus
clear from the table that SiO2 as a support is superior to other
supports in terms of time and yield. The effect of SiO2 may be
due to good dispersion of P2O5 on the surface of silica gel
leading to significant improvements in its reactivity.
conditionsa
Entry
P2O5/SiO2 (g)
Timeb (min)
Yieldc (%)
1
2
3
4
0.025
0.05
0.075
0.1
8
2
2
2
76
99
99
99
The scope and generality of this environmentally benign
method was further demonstrated by the reaction of hetero-
cyclic aldehyde 1 with different active methylene compounds
2a–k under solvent-free condition. All the reactions proceeded
smoothly and were completed within 2–9 min to afford the
products 3a–k in excellent yields (95–99%) (Table 8). However,
the reaction of heteroaldehyde 1 with triacetic acid lactone 2l,
6,7-dimethyl-4-hydroxycoumarin 2m and 4-hydroxycoumarin
2n did not give the expected Knoevenagel condensation pro-
ducts; instead, it afforded pyrazolo pyrones 3l, 3m and 3n in a
very short time (Table 8). The structure of newly synthesised
compound 3m was confirmed on the basis of spectral analysis
(FT-IR, 1H NMR, 13C NMR and mass spectra). The IR spectrum
of 3m showed sharp and strong absorption bands at 1726 cmÀ1
and 3377 cmÀ1 for the carbonyl and hydroxyl groups of the
coumarin moiety, respectively. Proton nuclear magnetic reso-
nance spectroscopy (1H NMR) exhibited sharp singlets at d 2.34,
d 2.39 and d 2.43 for the methyl groups of the pyrazole and
coumarin moiety, respectively. Another singlet integrating
for one proton at d 7.07 was assigned to the methine proton.
a
Reaction conditions: 5-chloro-3-methyl-1-phenylpyrazole-4-carboxalde-
hyde (1.0 mmol), 1,3-dimethyl barbituric acid (1.0 mmol), catalyst 0.05 g,
T = 80 1C. The reaction work-up was carried out as detailed under
b
c
Section 2. Reaction progress monitored by TLC. All yields refer to
isolated yield.
Table 7 Effect of different supports on the synthesis of 3a in thermal solvent-
free conditionsa
Entry
Support
Timeb (min)
Yieldc (%)
1
2
3
4
5
—
17.5
2
4
4.5
5.5
67
99
79
65
53
Silica gel
Acidic Alumina
Basic Alumina
Neutral Alumina
a
Reaction conditions: 5-chloro-3-methyl-1-phenylpyrazole-4-carboxalde-
hyde (1.0 mmol), 1,3-dimethyl barbituric acid (1.0 mmol), catalyst 0.05 g,
T = 80 1C. The reaction work-up was carried out as detailed under
b
c
Section 2. Reaction progress monitored by TLC. All yields refer to
isolated yield.
Table 8 P2O5/SiO2 catalyzed Knoevenagel condensation under thermal solvent-free conditionsa
Entry
2a–n
Product
Time (min)
Yieldd (%)
3ab
2
99
3bb
3cb
3db
3
6
4
98
97
97
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Table 8 (continued )
Entry
2a–n
Product
Time (min)
Yieldd (%)
3eb
9
95
3fb
8
96
3gb
5
98
3hc
3
98
3ib
5
96
3jb
3
98
3kb
2
98
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Table 8 (continued )
Entry
2a–n
Product
Time (min)
Yieldd (%)
3lb
4
95
3mc
3
96
3nb
4
95
a
Reaction conditions: 5-chloro-3-methyl-1-phenylpyrazole-4-carboxaldehyde (1.0 mmol), different active methylene compounds 2a–k (1.0 mmol)
b
and 2l–n (2.00 mmol), catalyst 0.05 g, T = 80 1C. The reaction work-up was carried out as detailed under Section 2. The products were confirmed
by melting points and compared with reported literature.60,61 c New compounds. All yields refer to isolated yield.
d
Nine aromatic protons appeared as a multiplet in the region
d 7.34–8.35. The 13C NMR spectrum showed signals at d 183.17
and d 166.52 for the hydroxyl and carbonyl carbons of the
coumarin moiety, respectively, and other carbon signals
appeared at their appropriate positions. Further confirmation
of the structure was provided by mass spectrometry which
showed M+ + 1 at m/z 547.
Scheme 2 Synthesis of 3(a–n) under thermal solvent-free conditions.
Fig. 7 Recyclability of the catalyst for the model reaction.
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Fig. 8 The SEM image of recovered catalyst after five runs at different magnifications.
Fig. 9 EDX analysis of the recovered catalyst after five runs (P2O5/SiO2).
Fig. 10 ORTEP structure of the Knoevenagel condensation product (3a), with 30% probability of thermal ellipsoids.
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as an efficient catalyst. The present protocol offers attractive
features such as excellent yields of the products in short
times, simple work-up procedure, environmentally benign
and economic viability and reusability of the catalyst. We
believe that this method provides a better scope for the syn-
thesis of heterocyclic alkene derivatives through Knoevenagel
condensation and will be a more practical alternative to the
other existing methods.
Acknowledgements
The authors are thankful to the SAP scheme (DRS-I) from the
University Grants Commission, New Delhi, Department of
Chemistry, IIT, Delhi for the single crystal diffractometer,
Centre of Excellence in Materials Science (Nanomaterials),
Department of Applied Physics, and University Sophisticated
Instrument Facility (USIF), AMU, Aligarh for providing powder
X-Ray diffractometer, SEM-EDX and TEM facilities. One of the
authors (T.K.) would like to acknowledge the University Grant
Commission (UGC), New Delhi, for the financial assistance in
the form of a Junior Research Fellowship [F. 17-43/08 (SA-I)].
Fig. 11 Packing diagram of the product 3a.
A recyclability test of the catalyst was performed in order to
satisfy the green chemistry criteria. The solid catalyst recovered
after the reaction by filtration was washed twice with ethyl
acetate (5 mL Â 2), and activated at 100 1C under static
conditions for 2 h. Fresh quantities of 1 and 2a were used
and the obtained catalyst was reused in the next reaction cycle.
The catalyst was successfully reused five times under similar
reaction conditions giving high conversions in the range 96–99%,
without any significant change in the catalytic activity and
morphology of the catalyst even after five reaction cycles
(Fig. 7). The recycling result suggests heterogeneity of the
catalyst. It is worth mentioning here that for every cycle the
catalyst was tested for the reaction at microscale.
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