Silica supported sodium hydrogen sulfate (NaHSO4-SiO 2): A novel, green catalyst for synthesis of pyrazole and pyranyl pyridine derivatives under solvent-free condition via heterocyclic β-enaminones

Article abstract of DOI:10.1016/j.molcata.2012.07.024

NaHSO₄-SiO₂ is used as an efficient, mild and reusable catalyst for the synthesis of novel heterocyclic pyrazole (5a-h) and pyranyl pyridine (7a-h) derivatives via heterocyclic β-enaminones (3a-d) under thermal solvent-free conditions. The remarkable features of this green, new methodology are high conversions, cleaner reaction profile, simple experimental and work-up procedures. Structures of the newly synthesized compounds have been elucidated on the basis of elemental analysis and spectral data (IR, ¹H NMR, ¹³C NMR and mass spectrometry). The catalyst is characterized for the first time by using scanning electron microscopy-energy dispersive X-ray (SEM-EDX) and powder XRD. The catalyst can be reused several times without significant loss of its catalytic activity.

Full text of DOI:10.1016/j.molcata.2012.07.024

Journal of Molecular Catalysis A: Chemical 363–364 (2012) 451–459
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Journal of Molecular Catalysis A: Chemical
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Silica supported sodium hydrogen sulfate (NaHSO4–SiO2): A novel, green catalyst
for synthesis of pyrazole and pyranyl pyridine derivatives under solvent-free
condition via heterocyclic ␤-enaminones
Zeba N. Siddiqui∗, Farheen Farooq
Department of Chemistry, Aligarh Muslim University, Aligarh, 202 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 May 2012
Received in revised form 19 July 2012
Accepted 20 July 2012
Available online 27 July 2012
NaHSO4–SiO2 is used as an efficient, mild and reusable catalyst for the synthesis of novel heterocyclic
pyrazole (5a–h) and pyranyl pyridine (7a–h) derivatives via heterocyclic ␤-enaminones (3a–d) under
thermal solvent-free conditions. The remarkable features of this green, new methodology are high con-
versions, cleaner reaction profile, simple experimental and work-up procedures. Structures of the newly
synthesized compounds have been elucidated on the basis of elemental analysis and spectral data (IR, 1
H
NMR, 13C NMR and mass spectrometry). The catalyst is characterized for the first time by using scanning
electron microscopy–energy dispersive X-ray (SEM–EDX) and powder XRD. The catalyst can be reused
several times without significant loss of its catalytic activity.
Keywords:
NaHSO4–SiO2
Heterocyclic ␤-enaminones
Pyrazoles
© 2012 Elsevier B.V. All rights reserved.
Pyranyl pyridines
Heterogeneous catalyst
1. Introduction
(NaHSO4–SiO2) has been found to be an efficient, inexpensive, non
toxic, recyclable and ecofriendly heterogeneous catalyst in various
Development of new solid-phase (solvent-free) reactions and
transferring solution phase reactions to solid-phase are subjects of
recent interest in the context of generating libraries of molecules for
the discovery of biologically active leads and also for the optimiza-
tion of drug candidates [1]. Hence, the challenges facing chemist
this century is to develop new transformations that are not only
efficient, selective and high yielding but also environmentally
benign. A solvent-free organic reaction is an important synthetic
strategy from the viewpoint of green and sustainable chemistry.
Researchers have demonstrated that the solvent-free organic syn-
theses are generally faster, selective, higher yielding with cleaner
products, environmentally benign and involve simple operational
procedure as compared to the classical reaction [2].
Heterogeneous catalysts have gained much importance in
recent years due to economic and environmental considerations.
These catalysts are advantageous over homogeneous catalysts as
they can be easily recovered from the reaction mixture by simple
filtration and can be reused after activation, thereby making the
process economically viable. A tremendous interest has sparked
in various chemical transformations promoted by catalysts under
heterogeneous conditions [3,4]. Silica supported sodium bisulfate
useful chemical transformations such as protection and deprotec-
tion [5], Knovenagel condensation [6], and Biginelli reaction [7]. It
is also used in the synthesis of dihydropyridines [8], xanthenes [9],
homoallylic amines [10], pyrazolines [11], amides [12], quinazoli-
nones [13], and imidazoles [14].
Pyrazole ring is an important structural motif present in numer-
ous pharmacological and agrochemically important compounds,
including inhibitors of HIV-I reverse transcriptase [15] and cele-
coxib derivatives as anti inflammatory agent [16]. Pyrazoles can
be synthesized by 1,3-dipolar cycloadditions of diazo compounds
[17], reaction of chalcones and hydrazines [18], a four-component
coupling of terminal alkynes, hydrazine, carbon monoxide and
aryl iodides [19] and the direct condensation of 1,3-diketones and
hydrazines in fluoroalcohol [20]. A variety of other catalysts such
as H2SO4 [21], polystyrene supported sulfonic acid [22], zirconium
sulfophenyl phosphonate [23], Sc (OTf)3 [24], Y-zeolite [25], Mg
(ClO4) [26] have been also employed to affect this transformation.
On the other hand, pyridine is one of the most prevalent het-
erocycle being the core fragment of different natural products
and pharmaceutical active agents [27]. In addition to classical
pyridine syntheses such as the Kröhnke reaction, many new
approaches have been also reported in the literature including
condensation of amines and carbonyl compounds, cycloaddition
reactions, multicomponent reaction [28–31] etc. Despite the wide
range of conceptually different syntheses of pyrazole and pyridine
∗
Corresponding author. Tel.: +91 9412653054.
E-mail address: siddiqui zeba@yahoo.co.in (Z.N. Siddiqui).
1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2012.07.024

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Z.N. Siddiqui, F. Farooq / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 451–459
Table 1
derivatives only few approaches toward these heterocyclic struc-
ture employing ␤-enaminones, active methylene compounds and
hydrazine derivative have been disclosed in the literature [32].
However, in spite of their potential utility, some of the reported
methods suffer from certain drawbacks such as long reaction time,
expensive reagents, harsh reaction conditions, low product yields
and high temperature. Therefore, improvements in these reaction
conditions required the development of efficient, cost effective,
safe, mild and environmentally benign procedures. Thus, based
on the above findings and in continuation of our interest in the
development of new methodologies [33], we report herein, the
use of silica supported sodium bisulfate (NaHSO4–SiO2) as a mild,
highly efficient, and recyclable heterogeneous catalyst for the syn-
thesis of pyrazole and pyranyl pyridine derivatives by the reaction
of ␤-enaminone with different hydrazines and active methylene
compounds respectively under thermal solvent-free condition in
excellent yields. The catalyst was recyclable up to four cycles.
The structure and morphology of the catalyst was established for
the first time with the help of powder XRD, scanning electron
microscopy (SEM) and energy dispersion analytical X-ray (EDX).
Synthesis of ␤-enaminonesa (3a–d) and their derived pyrazolesb (5a–h).
Entry
Product
R
Timec (min)
Yieldd (%)
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
5a
5b
5c
5d
5e
5f
–
–
–
–
H
Ph
H
Ph
H
Ph
H
5
5
10
10
5
5
5
5
10
10
10
10
93
92
89
92
94
90
92
92
87
85
90
89
10
11
12
5g
5h
Ph
a
Reaction conditions: heterocyclic methyl ketones (1a–d, 1.00 mmol) and DMF-
DMA (2, 1.00 mmol) heated under thermal solvent-free condition.
b
Reaction conditions: ␤-enaminones (3a–d, 1.00 mmol), hydrazines
(4a–b,1.00 mmol), and NaHSO4–SiO2 (100 mg) heated under solvent-free condition.
c
Reaction progress monitored by TLC.
Isolated yields.
d
obtained was filtered, washed with water, dried and recrystallized
from ethanol to afford pure products 3a–d.
2. Experimental
2.1. General
2.4. General procedure for the synthesis of pyrazoles under
thermal solvent-free condition
Melting points of all synthesized compounds were taken in a
Riechert Thermover instrument and are uncorrected. The IR spec-
tra (KBr) were recorded on Perkin Elmer RXI spectrometer. 1H NMR
and 13C NMR spectra were recorded on a Bruker DRX-300 and
Bruker Avance II 400 spectrometer using tetramethylsilane (TMS)
as an internal standard and DMSO-d6/CDCl3 as solvent. DART-MS
were recorded on a JEOL-Accu TOF JMS-T100LC mass spectrometer
having a DART source. Elemental analyses (C, H and N) were con-
ducted using the Elemental vario EL III elemental analyzer and their
results were found to be in agreement with the calculated values.
5-Acetyl-barbituric acid, 5-acetyl-1,3-dimethylbarbituric acid and
3-acetyl-4-hydroxycoumarin were synthesized by reported proce-
dures [34]. Other chemicals were of commercial grade and used
without further purification. The homogeneity of the compounds
was checked by thin layer chromatography (TLC) on glass plates
coated with silica gel G254 (E. Merck) using chloroform–methanol
(3:1) mixture as mobile phase and visualized using iodine vapors.
X-ray diffractograms (XRD) of the catalyst were recorded in the
2ꢀ range of 10–70◦ with scan rate of 4◦/min on a Rigaku Minifax
X-ray diffractometer with Ni-filtered Cu K␣ radiation at a wave-
length of 1.54060 ◦A. The SEM–EDX characterization of the catalyst
was performed on a JEOL JSM-6510 scanning electron microscope
equipped with energy dispersive X-ray spectrometer operating at
20 kV.
To a mixture of 3a–d (1.00 mmol) and hydrazine hydrate
(4a)/phenyl hydrazine (4b) (1.00 mmol), NaHSO4–SiO2 (100 mg)
was added. The reaction mixture was heated at 70 ◦C for speci-
fied time (Table 1). After completion of the reaction (checked by
TLC), the reaction mixture was cooled to room temperature and
mixed thoroughly with 10 mL of ethyl acetate. The solid inorganic
material was filtered off. After separation of solid, the solvent was
evaporated under reduced pressure. The white solid, thus, obtained
was washed with water and dried. Further purification was made
by recrystallization from ethanol to afford pure products 5a–h.
2.5. General procedure for the synthesis of pyranyl pyridine
derivatives under solvent-free condition
To a mixture of ␤-enaminone 3a (1.00 mmol), active methylene
compounds 6a–h (1.00 mmol), ammonium acetate (3.00 mmol),
NaHSO4–SiO2 (100 mg) was added. The reaction mixture was
heated at 70 ◦C over a heating mantle for specified time. After com-
pletion of the reaction (monitored by TLC) the contents were cooled
to room temperature and mixed thoroughly with (10 mL) of ethyl
acetate. The catalyst was removed by filtration and reused. After
separation of catalyst, the solvent was evaporated under reduced
pressure. The resulting solid residue was washed with cold water
to remove any unreacted ammonium acetate, filtered and dried
to afford the crude products. The pure product was obtained by
recrystallization from ethyl alcohol.
2.2. Preparation of catalyst
The catalyst silica-supported sodium hydrogen sulfate
(NaHSO4–SiO2) was prepared by reported procedure [35].
2.3. General procedure for the synthesis of heterocyclic
ˇ-enaminones under thermal solvent-free condition
3. Results and discussion
3.1. Characterization of the catalyst
A
mixture of dehydroacetic acid/3-acetyl-4-hydroxy-
coumarin/5- acetylbarbituric acid/5-acetyl-1,3-dimethylbarbituric
acid (1a–d) (1.00 mmol) and DMF-DMA (2) (1.00 mmol) was added
into a round bottom flask. The resulting mixture was heated at
70 ◦C in an oil bath for specified time (Table 1). The progress of
reaction was monitored by TLC. The reaction mixture (after being
cooled to room temperature) was poured into ice cold water
(20 mL) and stirred for 5–10 min. The bright yellow solid, thus,
3.1.1. Powder X-ray diffraction (XRD) analysis of the catalyst
The structure of the prepared catalyst (NaHSO4–SiO2) was
identified by powder XRD. X-ray patterns of the catalyst was
recorded at 2ꢀ = 10–70◦ range (Fig. 1). A broad peak centered at 2ꢀ
angle in the range 18–30◦ confirmed the formation of amorphous
silica–NaHSO4 matrix [36].

Z.N. Siddiqui, F. Farooq / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 451–459
453
consideration of all these limitations we have developed a sim-
pler and clean protocol for the synthesis of ␤-enaminones at lower
temperature. As a preliminary study, we first investigated the
synthesis of heterocyclic ␤-enaminones 3a–d by condensation of
heterocyclic methyl ketones 1a–d with N,N-dimethylformamide
dimethylacetal (DMF-DMA) (2) by thermal heating under solvent-
and catalyst-free condition at 70 ◦C for 5–10 min. The correspond-
ing enaminones (3a–d) were obtained in excellent yields (89–93%)
(Table 1).
The structure of isolated ␤-enaminones 3a–d (Scheme 1) was
verified by elemental analyses and spectroscopic data (IR, 1H NMR,
13C NMR and MS). The infrared (IR) spectrum of 3a exhibited the
broad band for OH group at 3429 cm−1 and a sharp strong band
at 1712 cm−1 for lactone carbonyl group. Another absorption band
at 1609 cm−1 along with a shoulder at 1649 cm−1 was due to C
C
and C O of ␣,␤-unsaturated system. The 1H NMR spectrum dis-
played two doublets at ı 6.65 and 8.05 with coupling constant
J = 12.3 Hz assignable to the two olefinic protons Ha and Hb respec-
tively. The coupling constant value indicates that the 3a existed
predominantly in the E-configuration (Scheme 1). The remaining
methyl and heterocyclic moiety protons were present at their nor-
mal values. The 13C NMR spectrum showed signal at ı 185.9 for
␣,␤-unsaturated carbonyl group whereas olefinic carbons C-2ꢀ and
C-3ꢀ were present at ı 91.5 and 156.8 respectively and other carbon
signals appeared at their appropriate positions. Further, evidence
for the formation of 3a was obtained by mass spectrum which
showed molecular ion peak at (m/z) 223.
10
20
30
40
50
60
2
θ
(degree)
Fig. 1. The powder XRD pattern of fresh catalyst.
3.1.2. SEM–EDX analysis of the catalyst
To study the surface morphology of the catalyst, SEM micro-
graphs of the catalyst was employed. The SEM images of the catalyst
(Fig. 2) showed an even distribution of NaHSO4 on the surface of the
silica gel. No conglomeration or layering of NaHSO4 was observed
on the surface of silica gel.
Further, EDX analysis (Fig. 3) of the catalyst showed the presence
of Na, S, O and Si elements suggesting the formation of expected
catalytic system.
3.3. Catalytic reaction
The increased reactivity of NaHSO4 supported on silica material
may be due to the catalyst and support interactions resulting in
the changes in surface properties of reactive sites. To the best of
our knowledge there is no report on the characterization of the
catalyst (NaHSO4–SiO2) using SEM–EDX study.
In order to study the generality of our methodology toward
heterocyclic compounds, the synthesis of pyrazole and pyridine
derivatives was explored. In our initial investigations for optimiza-
tion of appropriate reaction conditions, at first the synthesis of
compound 5a was selected as a model reaction. Thus, an equimo-
lar mixture of ␤-enaminone (3a) and hydrazine hydrate (4a) was
heated at 70 ◦C under solvent-free neat condition. The reaction pro-
ceeded very slowly and product was obtained in lower yield even
after prolong heating (Table 2, entry 1) demonstrating the need
of a catalyst. A comparative study was also carried out using dif-
ferent catalysts such as P2O5–SiO2, Zn(CH3COO)2, Zn(NO3)2, ZnCl2
AlCl3, FeCl3, Zn(l-proline)2, PTS, and l-proline and it was observed
that either reactions were not successful or products were obtained
in poor yields. When the model reaction was performed in the
presence of NaHSO4–SiO2 (100 mg) under solvent-free condition,
product 5a was obtained in excellent yield (94%) within shorter
time (5 min) (Table 2, entry 2).
3.2. Synthesis of heterocyclic ˇ-enaminones
␤-Enaminones have been used as valuable intermediates for the
synthesis of a vast variety of pharmacologically active compounds
[37]. Various method for the synthesis of ␤-enaminones have
been reported including condensation of active methyl and active
methylene compounds with N,N-dimethylformamide dimethylac-
etal under reflux condition or by using microwave irradiation [38].
These methods suffer from drawbacks such as higher temperature
and longer reaction time to achieve moderate to high yields of the
products. Martins et al. reported an efficient ionic liquid catalyzed
synthesis of ␤-enaminones using [Bmim].BF4 and [Omim].BF4 as
catalysts under solvent-free conditions [39]. However, ionic liq-
uids especially imidazolium based systems containing BF4 anions
are toxic in nature as they liberate hazardous HF and their high
cost and disposability make their utility limited [40]. Taking into
3.3.1. Effect of different supports
To establish the use of silica as the best support for NaHSO4,
other supports were also investigated (Table 2). The model
Fig. 2. SEM images of the catalyst (NaHSO4–SiO2) at different magnifications.

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Z.N. Siddiqui, F. Farooq / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 451–459
Fig. 3. EDX analysis of the catalyst (NaHSO4–SiO2).
reaction, thus, when carried out with NaHSO4–alumina (acidic,
basic, neutral), the TLC showed formation of product but the reac-
tion did not complete even after longer reaction time (Table 2,
entries 3,4,5). Further, when the silica gel alone was employed
in lieu of NaHSO4–SiO2, no measurable product was obtained
(Table 2, entry 6) while with NaHSO4 in pure form the reaction
was again not successful (Table 2, entry 7). Among the examined
supports, for NaHSO4, silica gel showed the best results. Therefore,
silica-supported NaHSO4 was used as catalyst for all reactions. The
increase in rate of reaction employing NaHSO4–SiO2 may be due
Scheme 1. Synthesis of heterocyclic ␤-enaminons (3a–d) and pyrazoles (5a–h).
Scheme 2. Proposed mechanism for the formation of 5a.

Z.N. Siddiqui, F. Farooq / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 451–459
455
Table 2
The screening of different supports on the model reaction.a
Table 4
Effect of catalyst loading on the synthesis of 5a.a
Entry
Support
Timeb
Yieldc (%)
Entry
Catalyst (mg)
Timeb (min)
Yieldc (%)
1
2
3
4
5
6
7
No catalyst
NaHSO4–SiO2
NaHSO4–alumina (acidic)
NaHSO4–alumina (basic)
NaHSO4–alumina (neutral)
SiO2
4 h
5 min
–
–
–
43
94
1
2
3
4
5
40
60
80
100
120
45
35
10
5
58
74
89
94
94
Incomplete
Incomplete
Incomplete
Trace
5
3.5 h
3 h
a
Reaction conditions: ␤-enaminone (3a, 1.00 mmol), hydrazine hydrate (4a,
NaHSO4
52
1.00 mmol), heated under thermal solvent-free condition.
a
b
Reaction conditions: ␤-enaminone (3a, 1.00 mmol), hydrazine hydrate (4a,
1.00 mmol), and NaHSO4–SiO2 (100 mg) heated under thermal solvent-free con-
dition.
Reaction progress monitored by TLC.
c
Isolated yields.
b
Reaction progress monitored by TLC.
Isolated yields.
Table 5
c
Recycling data of the catalyst for the model reaction.a
Catalyst recycles
Timeb
Yieldc (%)
Table 3
Comparative study of compound 5a using solution conditions versus the solvent-
free method.
I
II
III
IV
V
5 min
5 min
5 min
5 min
10 min
94
94
94
94
89
Entrya
Solvent
Temperature
70 ◦
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Timeb
Yieldc (%)
1
2
3
4
5
6
7
Solvent-free
Acetic acid
EtOH
MeOH
Isopropanol
CH2Cl2
C
5 min
7 h
3 h
6 h
8 h
94
76
68
64
58
35
38
a
Reaction conditions: ␤-enaminone (3a, 1.00 mmol), hydrazine hydrate (4a,
1.00 mmol), and NaHSO4–SiO2 (100 mg) heated under thermal solvent-free con-
dition.
b
Reaction progress monitored by TLC.
Isolated yields.
48 h
48 h
c
CH3CN
a
Reaction conditions: ␤-enaminone (3a, 1.00 mmol), hydrazine hydrate (4a,
1.00 mmol), and NaHSO4–SiO2 (100 mg).
dissolved in ethyl acetate (10 mL). The mixture was filtered for sep-
aration of the catalyst. The recovered catalyst was washed with
ethyl acetate (3× 10 mL), dried in oven at 100 ◦C for 3 h and used
for the subsequent catalytic runs. The results (Table 5) showed that
the catalyst was active up to four cycles.
The identity of the recovered catalyst was checked by powder
XRD and SEM analysis. It was observed that peaks remained the
same (Fig. 4), and also there was no change in the morphology of
the catalyst (Fig. 5) as compared to the fresh catalyst.
b
Reaction progress monitored by TLC.
Isolated yield.
c
to increased surface area of the catalyst. A plausible mechanism
for the formation of 5a in the presence of NaHSO4–SiO2 has been
shown in Scheme 2.
3.3.2. Effect of solvents
In order to study the solvent effect, the model reaction was car-
ried out in different solvents such as acetic acid, dichloromethane
(CH2Cl2), acetonitrile (CH3CN), methanol (MeOH), ethanol (EtOH)
and isopropanol. When the reaction was performed in EtOH, MeOH,
isopropanol lower yield of the product (5a) was obtained after
longer time period (Table 3, entries 3, 4, 5) whereas in CH2Cl2 and
CH3CN, only trace amounts of the product was obtained (Table 3,
entries 6, 7). Using acetic acid relatively high yield of the product
was obtained (Table 3, entry 2) but reaction took longer time period
for completion. When the reaction was carried out under solvent-
free condition, both the yield and reaction time were significantly
improved (Table 3, entry 1).
Under these optimized reaction conditions the scope and
generality of the present method was further demonstrated by
reaction of different heterocyclic ␤-enaminones (3a–d) with vari-
ous hydrazine derivatives (4a–b) under solvent-free condition. All
the reactions proceeded smoothly and the reaction was completed
within 5–10 min to afford the products (5a–h) in excellent yields
(85–94%) (Table 1). The structure of products 5a–h (Scheme 1) was
deduced from their elemental analysis and spectral data (IR, 1H
NMR, 13C-NMR and MS). The IR spectrum of 5a showed two broad
absorption bands at 3171 cm−1 and 3045 cm−1 due to the pres-
ence of OH group of lactone and NH group of pyrazole moieties
3.3.3. Loading of the catalyst
In order to optimize the amount of catalyst used for the catal-
ysis of the reaction to form the desired product 5a, we analyzed
the reaction by varying the loading amount to 40, 60, 80, 100 and
120 mg of NaHSO4–SiO2. Generally, the rate of reaction and yield
increases over the amount of catalyst. It was found that the opti-
mum amount of catalyst turned out to be 100 mg in order to obtain
the best result. No such significant improvement in the yield was
observed on increasing the loading to 120 mg, whereas, decreasing
the amount of catalyst to 40 mg resulted in lowering of the yield
(Table 4).
3.3.4. Recycling study of the catalyst
We also investigated the reusability of the catalyst under
solvent-free condition using model reaction of ␤-enaminone (3a)
with hydrazine hydrate (4a) in the presence of NaHSO4–SiO2
(100 mg) (Table 5). After completion of the reaction, the mix-
ture was cooled to room temperature, and the organic part was
10
20
30
40
50
60
2θ (degree)
Fig. 4. The powder XRD pattern of recovered catalyst after four runs.

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Z.N. Siddiqui, F. Farooq / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 451–459
section. The structure of compound 5a was further confirmed by
mass spectrum which showed M+ at (m/z) 192.
3.4. Synthesis of pyranyl pyridine derivatives
Efforts were made to synthesize pyranyl pyridine derivatives
(7a–h) employing (3a) (1.00 mmol), different cyclic/acyclic active
methylene compounds (6a–h) (1.00 mmol) and ammonium acetate
(3.00 mmol) as an ammonia source in the presence of NaHSO4–SiO2
under same reaction conditions (Scheme 3).
All reactions proceeded efficiently and the desired products
were obtained in excellent yields (81–93%) in short reaction times
(5–25 min) (Table 6). The structure of compounds (7a–h) was
deduced on the basis of IR, 1H NMR, 13C NMR and mass spec-
trometry. The IR spectrum of the newly synthesized compound
(7a) exhibited characteristic absorption bands at 3065, 1717 and
1697 cm−1 due to the presence of OH, ester, and lactone carbonyl
groups respectively. 1H NMR exhibited two doublets at ı 8.85 and
8.44 for H4 and H5 proton of pyridine moiety. Presence of ester
group was inferred by quartet at ı 4.44 (J = 7.2 Hz) and triplet at
ı 1.42 (J = 6.9 Hz) for OCH2 and CH3 protons respectively. The 13C
NMR spectrum showed characteristic signals at ı 142.2 and 119.7
for C4 and C5 carbons of pyridine moiety respectively. Other peaks
were at their normal values and discussed in the experimental sec-
tion. Further confirmation for the structure 7a was provided by
mass spectrometry which showed M+ at 289.15 as base peak.
Fig. 5. The SEM image of recovered catalyst after four runs.
respectively. A sharp and strong absorption band for the lactone
carbonyl group was discernible at 1696 cm−1. In the 1H NMR spec-
trum the presence of pyrazole moiety was inferred by two doublets
at ı 6.91 (J = 3 Hz) and ı 7.89 (J = 3 Hz) for C-4ꢀ, C-3ꢀ protons respec-
tively and a broad singlet for NH proton at ı 13.36. The 13C NMR
spectrum showed signal at ı 145.6, 100.6, and 130.1 for C-3ꢀ, C-4ꢀ,
and C-5ꢀ carbons of pyrazole moiety. The other peaks were present
at their normal values and are mentioned in the experimental
Scheme 3. General scheme for the products formed by the reaction of (3a) with different active methylene compounds (6a–h), ammonium acetate catalyzed by NaHSO4–SiO2
at 70 ◦C.

Z.N. Siddiqui, F. Farooq / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 451–459
457
Table 6
Synthesis of compounds 7a–h.a
Entry
Product
Timeb (min)
Yieldc (%)
M.P. (◦C)
7a
5
93
129–131
7b
5
88
201–205
7c
10
89
>300
7d
10
84
>300
7e
15
81
>300

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Z.N. Siddiqui, F. Farooq / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 451–459
Table 6 (Continued)
Entry
Product
Timeb (min)
Yieldc (%)
M.P. (◦C)
7f
25
89
>300
7g
15
93
239–241
7h
20
90
>300
a
Reaction conditions: ␤-enaminone (3a, 1.00 mmol), active methylene compounds (6a–h, 1.00 mmol), ammonium acetate (3.00 mmol), and NaHSO4–SiO2 (100 mg) heated
under solvent-free condition.
b
Reaction progress monitored by TLC.
Isolated yields.
c
4. Conclusion
Appendix A. Supplementary data
In summary, this paper describes a convenient and efficient
process for the synthesis of novel pyrazole and pyranyl pyri-
dine derivatives under thermal solvent-free conditions using
NaHSO4–SiO2 as an efficient catalyst. Present methodology offers
very attractive features as excellent yields of the product in shorter
reaction time, simple work-up procedure, economic viability and
reusability of the catalyst and first time synthesis of hitherto
unknown heterocyclic ␤-enaminones at lower temperature. We
believe that this method has provided a better scope for the synthe-
sis of pyrazole and pyridine derivatives and will be a more practical
alternative to the other existing methods.
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.molcata.
2012.07.024.
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