Sulphated silica tungstic acid as a highly efficient and recyclable solid acid catalyst for the synthesis of tetrahydropyrimidines and dihydropyrimidines

Article abstract of DOI:10.1016/j.molcata.2014.02.019

For the first time sulphated silica tungstic acid (SSTA) has been synthesized and used as an acidic catalyst in organic synthesis. The catalyst was prepared by a simple method based on the reaction of silica with SOCl ₂ followed by addition of

Full text of DOI:10.1016/j.molcata.2014.02.019

Journal of Molecular Catalysis A: Chemical 387 (2014) 45–56
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Sulphated silica tungstic acid as a highly efficient and recyclable solid
acid catalyst for the synthesis of tetrahydropyrimidines and
dihydropyrimidines
Nayeem Ahmed, Zeba N. Siddiqui∗
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:
For the first time sulphated silica tungstic acid (SSTA) has been synthesized and used as an acidic catalyst
in organic synthesis. The catalyst was prepared by a simple method based on the reaction of silica with
SOCl2 followed by addition of sodium tungstate and then functionalization with chlorosulfonic acid. The
three-component Biginelli-like condensation of different heteroaldehydes, urea and ethyl cyanoacetate
or phenyl acetic acid catalyzed by SSTA under solvent-free conditions afforded novel tetrahydropyrim-
idines in high yields. The catalyst tolerated different heteroaldehydes and also catalyzed the synthesis
of Biginelli compounds efficiently giving excellent yield of products. The catalyst was characterized by
FT-IR, XRD and SEM-EDX analyses. The stability of the catalyst was evaluated by DSC and TG analyses.
The major advantages of the present method are high yields, short reaction times, and solvent-free reac-
tion conditions. The activity and simple recyclability without losing catalytic activity make this catalyst
a good replacement to literature methods.
Received 9 December 2013
Received in revised form 16 February 2014
Accepted 18 February 2014
Available online 4 March 2014
Keywords:
SSTA
Tetrahydropyrimidines
Heterogeneous
Solvent-free
Recyclability
© 2014 Elsevier B.V. All rights reserved.
1. Introduction
made for specific applications with the use of a combination of
inorganic materials and functional groups which often result in syn-
The catalysts which make the organic reactions environmen-
tally benign and economically feasible are extremely demanded by
the chemical industries. In recent years, preparation of new hetero-
geneous catalysts with improved efficiency has been the subject of
immense interest [1]. The ideal method for combining the advan-
tages of homogeneous catalysts (high activity and selectivity, etc.)
with the advantages of heterogeneous catalysts (available active
sites, easy catalyst separation, long catalytic life, thermal stabil-
ity, low hygroscopic properties, easy handling and reusability) is
by immobilization of catalysts on solid support, which leads to
clean chemical synthesis from both environmental and commercial
point of view [2–5]. In modern material science, silica is the ubiq-
uitous inorganic platform used in systems designed for catalysis,
separation, filtration, sensing, optoelectronics and environmental
technology. Due to the favourable chemical and physical proper-
ties of silica surfaces, it is possible to impart nearly any reactive
functional group that one requires on a silica surface (e.g., sulfonic,
amine, carboxyl, thiol, epoxy, and so forth) through well-known
silane chemistry [6–8]. As a result, numerous variations can be
ergetic effects that lead to increased physical stability and enhanced
chemical functionality [9,10].
The Biginelli multicomponent reaction is
a very elegant
methodology to obtain 3,4-dihydropyrimidin-2(1H)-one (DHPMs)
derivatives in a one-step procedure [11]. DHPMs usually display
various biological activities such as calcium channel modula-
tors, adrenergic receptor antagonists, mitotic kinesin inhibitors,
antivirals, antibacterials [12] and compounds such as enastron,
monastrol, piperastrol and other derivatives [13] are well known
biologically active compounds which have already been developed
into drugs.
Moreover tetrahydropyrimidine ring is found in both natural
as well as synthetic organic compounds. Many tetrahydropyrim-
idines containing an amino acid show interesting and diverse
pharmacological activities like HIV protease inhibiting activity
[14], antineoplastic activity [15], antiproliferative [16], herbicidal
activity [17], muscarinic agonist activity [18], anti-inflammatory
[19] and antiviral properties [20]. The presently known MCR
protocols for the synthesis of THPMs are via Biginelli-like trans-
formation [21] or alternatively, using the two-step operation of
Knoevenagel condensation and urea annulation [22]. To the best of
our knowledge, not a single multicomponent protocol for the syn-
thesis of THPMs tolerating heteroaldehydes under heterogeneous
∗
Corresponding author. Tel.: +91 9412653054.
E-mail address: zns.siddiqui@gmail.com (Z.N. Siddiqui).
http://dx.doi.org/10.1016/j.molcata.2014.02.019
1381-1169/© 2014 Elsevier B.V. All rights reserved.

46
N. Ahmed, Z.N. Siddiqui / Journal of Molecular Catalysis A: Chemical 387 (2014) 45–56
conditions is presently available. It is therefore highly desirable to
develop new methods for the efficient synthesis of THPMs. In the
present work, taking advantage of the above mentioned properties
of silica, we have designed and synthesized novel, sustainable
sulphated silica immobilized tungstic acid (SSTA) and as our
continuous efforts in developing novel protocols for the synthesis
of useful heterocyclic scaffolds [23], we wish to report herein, SSTA
catalyzed novel three-component synthesis of THPMs by using
different heteroaldehydes, cyanoethyl acetate/phenylacetic acid
and urea under solvent-free conditions.
2.4. Preparation of sulphated silica tungstic acid (S-STA)
A 0.5 L suction flask was equipped with a constant pressure
dropping funnel. The gas outlet was connected to a vacuum system
through an adsorbing solution of alkali trap. STA (2.5 g) was added
into the flask and stirred for 10 min in dry CH2Cl2 (0.075 L). Chloro-
sulfonic acid (1.75 g) was added drop wise over a period of 30 min
at room temperature. After completion of the addition, the mix-
ture was stirred for 90 min, while the residual HCl was eliminated
by suction. Then the sulphated-STA was separated from the reac-
tion mixture and washed several times with dried CH2Cl2. Finally
sulphated-STA was dried at 120 ◦C for 3 h.
2. Experimental
2.5. General procedure for synthesis of tetrahydropyrimidines
2.1. General
Aldehyde (3 mmol), ethyl cyanoacetate or phenyl acetic acid
(3 mmol), urea (4.5 mmol) and SSTA (200 mg) were mixed by stir-
ring in a 25 mL round bottom flask for specified time (Table 4)
at a temperature of 70 ◦C. The reaction mixture was cooled and
ethanol was added to solubilize the product. The remaining solid
catalyst was filtered, washed with ethanol (3 × 15 mL) and ethyl
acetate (2 × 10 mL) and reused for further catalytic cycles. The fil-
trate was evaporated under reduced pressure to obtain the product.
The crude product was further purified by recrystallization from
suitable solvent (ethanol or DMSO).
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-400 spec-
trometer using tetramethylsilane (TMS) as an internal standard and
DMSO-d6/CDCl3 as solvent. Mass spectra were recorded on Micro-
mass Quattro II (ESI) spectrometer. Elemental analyses (C, H and N)
were conducted using the Elemental vario EL III elemental analyzer
and their results were found to be in agreement with the calcu-
lated values. DSC, TGA and DTA data were obtained with DSC-60
Shimadzu instrument. X-ray diffractograms (XRD) of the catalyst
were recorded in the range of 0–80 with scan rate of 4◦/min on a
Rigaku Minifax X-ray diffractometer with Ni-filtered Cu K␣ radia-
2.6. General procedure for synthesis of dihydropyrimidines
Aldehyde (3 mmol), ethyl acetoacetate or acetyl acetone
(3.5 mmol), urea (4.5 mmol) and SSTA (200 mg) were mixed in a
25 mL round bottom flask for specified time (Table 4) at a tempera-
ture of 70 ◦C. The reaction mixture was cooled and added ethanol to
solubilize the product. Catalyst was recovered by above-mentioned
procedure. The filtrate was evaporated under reduced pressure
to obtain the product. The compounds were recrystallized from
ethanol.
˚
tion at a wavelength 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. DSC analysis was performed in the tempera-
ture range of 20–500 ◦C, DTA and TGA analyses were performed
in the temperature range of 0–1000 ◦C at a constant heating rate
of 20 ◦C/min in the nitrogen atmosphere. All solvents and chemi-
cals used were AR grade. The purity of 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 by iodine vapours and alcoholic ferric
chloride. All acid catalysts such as SiO2–OSO3H [24], ZrO2–OSO3H
[25], NH2SO3H–SiO2 [8], cellulose–OSO3H [26], xanthan–OSO3H
[27], PEG–OSO3H [28] used in optimization study were synthesized
by reported procedures.
3. Result and discussion
The SSTA catalyst was prepared by the concise route outlined
in Scheme 1. Sodium tungstate reacted with silica chloride to pro-
duce silica tungstic acid (STA) which on further sulfonation with
chlorosulfonic acid gave sulphated silica tungstic acid (SSTA). The
optimum concentration of H+ was determined by titration of the
aqueous suspension of the weighed amount of thoroughly washed
catalyst with standard NaOH solution. The strength of NaOH solu-
tion was kept very low (0.01 N) in order to minimize errors caused
by reaction of NaOH with Lewis acid groups and to avoid the con-
sumption of the base in the hydrolysis of the silica frameworks. The
optimum concentration of H+ was 0.40 mequiv/g of the support.
After successive experiments the concentrations of the residual
H+ on the recovered catalyst were measured (provided in recycling
study) which showed very small or marginal loss of H+. It signi-
fied that SO3H moiety was tightly anchored with STA, probably
through a covalent linkage. The reaction between 6-methyl-3-
formyl chromone, urea and ethylcyano acetate in the presence of
SSTA (preheated at 120 ◦C for 3 h) occurred with high efficiency giv-
ing 94% product yield and the reaction between 6-methyl-3-formyl
chromone, urea and ethylcyano acetate in the presence of SSTA
after keeping it at an ambient atmosphere for 5 days produced sim-
ilar observation. This showed that there was no deteriorating effect
of atmospheric oxygen or moisture towards the activity of the cat-
alyst. The catalyst thus, showed considerable stability towards heat
and moisture which provided further evidence for covalent linkage
and the potential of efficient recycling.
2.2. Preparation of silica chloride
SOCl2 (20 g) was added drop wise to the silica gel (20 g) in dry
CH2Cl2 (50 mL) at room temperature under stirring. Evolution of
copious amounts of HCl and SO2 occurred instantaneously. After
stirring for another 1 h, the solvent was removed under reduced
pressure. The silica chloride thus obtained was used in the following
experiments [29].
2.3. Preparation of silica tungstic acid
A mixture of silica chloride (6.00 g) and sodium tungstate
(7.03 g) in dry n-hexane (10 mL) was stirred under refluxing condi-
tions for 6 h. After completion of the reaction, the reaction mixture
was filtered, washed with distilled water, dried and then stirred in
the presence of 0.1 N HCl (40 mL) for an hour. Finally, the mixture
was filtered, washed thoroughly with distilled water, and dried to
afford STA [30].

N. Ahmed, Z.N. Siddiqui / Journal of Molecular Catalysis A: Chemical 387 (2014) 45–56
47
Scheme 1. Schematic representation of the synthesis of the catalyst.
3.1. FT-IR spectral analysis of the catalyst
3.2. XRD spectral analysis
In order to evaluate incorporation of sulfonic groups and tung-
sten moieties on silica surface, FT-IR spectra of the respective
sodium tungstate, STA and SSTA have been analyzed (Fig. 1). The
The XRD analysis showed that the XRD patterns of the cata-
lyst (Fig. 2b) were similar to that of the support (Fig. 2a). The WO3
group exhibits a broad peak around 2ꢀ = 22◦ which merges with the
2−
FT-IR spectrum of sodium tungstate shows the WO4 stretching
frequency at 1683 cm−1, STA showed this frequency at 1650 and
also showed peaks corresponding to SiO2 stretching. The intensity
2−
of WO4 stretching in STA decreased due to bonding with silica.
2−
The introduction of SO3 groups in STA led to further decrease in
the intensity of the WO4
2−
stretching. The SSTA also showed OH
stretching frequency at 3448 cm−1. The asymmetric and symmet-
ric stretching vibrations of SO3 group obtained around 1300 and
1200 cm−1 merged with the broad absorption peak between 1000
and 1500 cm−1, which showed some increase in intensity and little
increase in broadening compared to broad peak of STA. The SSTA
also showed the peaks corresponding to SiO2–Cl and SiO2 stretch-
ing. Thus the IR spectrum confirms the successful sulfonation of
STA.
Fig. 2. (a) Powder XRD pattern of SiO2 (b) XRD pattern of fresh SSTA (c) XRD pattern
Fig. 1. FT-IR spectra of (a) sodium tungstate (b) silica tungstic acid and (c) SSTA.
of the catalyst after six catalytic cycles.

48
N. Ahmed, Z.N. Siddiqui / Journal of Molecular Catalysis A: Chemical 387 (2014) 45–56
broad peak shown by SiO2 at around 2ꢀ = 20–25◦ [30,31]. This also
indicates that the acids are highly dispersed on the support surface.
Table 1
Effect of various reaction media for the model reaction.a
Entry
Catalyst
Condition
Timeb
Yield%c
3.3. SEM/EDX analysis of the catalyst
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
H2SO4 (10 mol%)
H2SO4 (10 mol%)
H2SO4 (10 mol%)
Ethanol/reflux
Iso-propanol/reflux
8 h
56
53
67
82
62
65
68
58
45
71
67
78
94
73
65
59
46
23
25
36
41
–
8.5 h
4.2 h
40 min
2 h
65 min
60 min
90 min
2.5 h
55 min
3.2 h
90 min
15 min
2 h
2.5 h
3.1 h
3.5 h
4.2 h
4.5 h
6 h
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
Ethanol/reflux
C
C
C
C
C
C
C
C
C
C
C
The SEM image (Fig. 3b) of the catalyst showed the surface mor-
phology of functionalized silica. The image shows the change in
the surface morphology of silica gel (Fig. 3a) upon functionaliza-
tion. Furthermore, the formation of expected sulphated catalytic
system was also confirmed by EDX analysis (Fig. 4) which showed
the presence of sulphur in addition to silicon and tungsten.
H2SO4-SiO2 (200 mg)
H2SO4–ZrO2 (200 mg)
H2SO4–cellulose (200 mg)
H2SO4–xanthan (200 mg)
H2SO4–PEG (200 mg)
CSA (200 mg)
NH2SO3H–SiO2 (200 mg)
Na2WO3 (10 mol%)
STA (200 mg)
STA–OSO3H (200 mg)
STA–OSO3H (200 mg)
STA–OSO3H (200 mg)
STA–OSO3H (200 mg)
STA–OSO3H (200 mg)
STA–OSO3H (200 mg)
STA–OSO3H (200 mg)
FeCl3 (10 mol%)
3.4. DSC/TG analysis of the catalyst
Thethermalstabilityof thecatalystwasevaluatedbyDSCandTG
analyses. The DSC graph (Fig. 5a) shows a small endothermic tran-
sition around 100 ◦C which is due to the loss of surface-physisorbed
water molecules on silica matrix. The graph further does not show
any transition up to 450 ◦C after which a peak begins to appear
which may be due to the loss of bonded sulphate groups. Thus it
can be inferred that the catalyst is stable up to 450 ◦C.
TG curve (Fig. 5b) provided further information about the ther-
mal stability of the catalyst. The TG curve showed a weight loss
of 19% around 100 ◦C which can be attributed to the loss of water
molecules present in silica gel framework. The catalyst then did not
show any further weight loss up to 550 ◦C. This confirms that the
catalyst is stable up to this temperature, shown also by DSC anal-
ysis. Further weight loss of ∼7% at 550 ◦C can be attributed to the
decomposition of sulphate groups from the surface of silica. Thus,
DSC and TG analyses showed that the catalyst can tolerate wide
range of temperature.
Iso-propanol/reflux
Methanol/reflux
CH2Cl2/reflux
Hexane/reflux
Toluene/reflux
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
Solvent-free/70 ◦
C
C
C
C
ZnCl2 (10 mol%)
ZnO (10 mol%)
MgO (10 mol%)
5.4 h
–
–
–
a
Reaction of 6-methyl-3-formylchromone (1 mmol), urea (1.5 mmol) and ethyl
cyanoacetate (1 mmol) in presence of different reaction media.
b
Reaction progress monitored by TLC.
Isolated yield.
c
we explored the behaviour of SSTA in different solvents. The use of
polar solvents like ethanol, methanol and isopropanol gave yields
better than non-polar solvents like hexane and toluene but still
were unsatisfactory than solvent-free approach.
3.5. Optimization of reaction conditions
3.5.2. Effect of catalyst loading
Taking SSTA under solvent-free condition as the right catalyst
for the experiment, we next investigated right amount of cata-
lyst for further optimization of reaction conditions. Performing the
reaction with a higher than 200 mg of catalyst had no significant
effect on yield. However, if the amount of the catalyst was reduced
to 150 and 100 mg, the product yield was reduced to 68% and 43%
respectively (Table 2). Therefore, 200 mg of SSTA at 70 ◦C under
solvent-free condition gave best results for the model reaction giv-
ing conversion of 94% in 15 min.
3.5.1. Effect of different reaction media
In order to determine the optimum conditions, the solvent
effect, the proportions of catalyst to substrate and the reaction
time were examined. At the beginning of this study, the reaction
of 6-methyl-3-formyl chromone, urea and ethylcyano acetate was
carried out in the presence of sulphuric acid in ethanol at reflux
temperature (Table 1). Use of sulphuric acid gave product 4b with
52% yield and the conversion was still low after 8 h (entry 1). Fur-
thermore, a nearly equal amount of the product 4b was observed,
using sulphuric acid under solvent-free condition at 70 ◦C, thereby
urging us to identify conditions that provide the product in good
yield in less time. As the solvent-free approach produced same yield
in less time, this approach was further explored for optimization of
reaction conditions. In the first optimization, the effect of the dif-
ferently supported sulphuric acids under solvent-free condition at
70 ◦C was examined. Organic polymers like cellulose, xanthan, PEG
and camphor supported sulphuric acid gave unsatisfactory yields.
Among silica and zirconia supported sulphuric acids the use of
silica–SO3H led to the preferential formation of 4b with good con-
version (entry 4). In order to further improve our protocol we then
turned our attention towards recently synthesized catalyst silica
tungstic acid (STA). The use of STA under solvent-free condition
showed results better than different organic polymers supported
acid but still unsatisfactory than silica–SO3H. As a facile means to
improve it, we then introduced SO3H groups in STA. This strategy
was found to be effective in decreasing not only the time period but
also increasing the product yield. The sulphated STA (SSTA) gave
94% product yield in 15 min. The efficiency of this catalytic system
was further tested by comparing it with different Lewis acids under
solvent-free condition. FeCl3 and ZnCl2 gave less product yield and
took 5–6 h to complete whereas ZnO and MgO could not show satis-
factory results. In order to further optimize the reaction conditions
3.5.3. Effect of temperature
The effect of temperature plays an important role in the catalytic
synthesis of tetrahydropyrimidines. It was examined in the tem-
perature range from room temperature to 100 ◦C in the absence of
solvent, using SSTA as catalyst. At room temperature the reaction
was not successful and with further increase in temperature the
yield of product increased with decrease in time taken for comple-
tion of the reaction. At 70 ◦C and 80 ◦C the reaction was completed
in 15 min with almost same yield. With further increase in the tem-
perature the yield of product decreased which may be due to the
Table 2
Effect of catalyst loading on the model reaction.a
Entry
Amount of catalyst (mg)
Time (min)b
Yieldc (%)
1
2
3
4
300
200
150
100
15
15
30
45
91
94
68
43
a
Reaction of 6-methyl-3-formyl chromone (1 mmol), urea (1.5 mmol) and ethyl
cyanoacetate (1 mmol) in presence of different amounts of SSTA under solvent-free
condition at 70 ◦C.
b
Reaction progress monitored by TLC.
Isolated yield.
c

N. Ahmed, Z.N. Siddiqui / Journal of Molecular Catalysis A: Chemical 387 (2014) 45–56
49
Fig. 3. SEM images (a) of SiO2 support (b) of freshly synthesized SSTA and (c) of recycled SSTA.
formation of some side product (Table 3). So 70 ◦C was chosen as
the optimum temperature for performing the reaction.
successfully. Further, on replacement of ethylcyano acetate with
phenyl acetic acid the reaction proceeded with little longer reac-
tion time, however, desired compounds were obtained in good
yields (Table 4). Thus, it was observed that the reaction tolerated
aldehydes with different heterocyclic substituents successfully to
furnish the final products in good yields.
3.6. Catalytic reaction
3.6.1. Synthesis of tetrahydropyrimidines
The structures of the final products were well characterized by
using spectral (IR, 1H, 13C NMR and ESI-MS) and elemental analy-
sis data. IR spectrum of 4b showed peaks at 3281 and 3446 cm−1
which were assigned to two secondary NH groups. The absorp-
tion band at 2924 cm−1 was assigned to CN stretching. The two
With these encouraging results in hand, we turned to explore
the scope of the reaction using different heterocyclic aldehydes,
ethylcyano acetate or phenyl acetic acid and urea as substrates
under the optimized reaction conditions (Scheme 2). The reac-
tion proceeded smoothly offering excellent yield of products
Fig. 4. EDX analysis of SSTA showing presence of S in addition to W and Si.

50
N. Ahmed, Z.N. Siddiqui / Journal of Molecular Catalysis A: Chemical 387 (2014) 45–56
Table 4
Synthesis of tetrahydropyrimidines and dihydropyrimidinones using SSTA catalyst under solvent free conditions at 70 ◦C.
Entry
1a–m
3a–d
Product (4a–w)
Time (min)a
Yield (%)b
O
O
O
NC
O
NH
CHO
O
O
N
1
16
91
N
H
O
O
O
1a
O
4a
O
O
NC
H3C
CHO
NH
O
O
N
H3C
2
O
15
94
N
H
O
1b
4b
O
O
O
NC
Cl
CHO
NH
O
O
O
Cl
N
3
15
90
N
H
O
O
1c
4c
O
CHO
NC
NH
O
N
H
N
O
N
4
20
88
H
O
O
N
H
1d
4d
O
O
HN
NH
O
CHO
O
5
6
7
21
20
20
87
90
86
O
OH
OH
OH
O
1a
4e
O
O
H3C
CHO
NH
HN
O
O
O
O
H3C
O
O
1b
4f
O
O
O
Cl
CHO
HN
NH
O
O
Cl
O
1c
4g
O
CHO
Cl
NH
O
8
25
85
N
H
O
N
OH
1e
N
Cl
4h

N. Ahmed, Z.N. Siddiqui / Journal of Molecular Catalysis A: Chemical 387 (2014) 45–56
51
Table 4 (Continued)
Entry 1a–m
3a–d
Product (4a–w)
Time (min)a
Yield (%)b
O
Cl
NH
CHO
O
Cl
O
O
9
31
82
N
H
O
O
OH
1f
O
O
4i
CHO
NH
O
N
H
N
H
O
10
22
84
OH
N
H
1d
4j
O
NH
O
O
CHO
11
23
83
N
H
O
OH
OH
1g
4k
O
NH
CH3CH2CHO
12
27
82
N
O
1h
H
4l
OEt
CH3
NH
O
O
O
O
H3C
CHO
O
O
O
O
O
O
13
O
H3C
10
94
N
O
H
1b
O
4m
CH3
CH3
CHO
O
NH
N
H
14
12
92
N
O
H
N
H
1d
4n
CHO
O
H3CH2CO
H3C
NH
15c
10
96
O
N
H
O
1i
4o

52
N. Ahmed, Z.N. Siddiqui / Journal of Molecular Catalysis A: Chemical 387 (2014) 45–56
Table 4 (Continued)
Entry
1a–m
3a–d
Product (4a–w)
Time (min)a
Yield (%)b
CHO
O
H3C
O
O
16c
12
95
NH
H3C
N
H
O
1i
4p
NO2
CHO
O
O
O
O
O
17c
08
95
H3CH2CO
H3C
NH
NO2
O
N
H
O
1j
4q
NO2
CHO
O
O
18c
10
94
H3C
NH
NO2
H3C
N
H
O
1j
4r
OH
CHO
O
O
19c
09
94
O
H3CH2CO
NH
OH
1k
H3C
N
H
4s
O
OH
CHO
O
O
O
20c
12
95
H3C
NH
OH
1k
H3C
N
H
O
4t
CHO
Cl
O
Cl
NH
O
O
21c
H3CH2CO
08
93
O
H3C
N
H
4u
O
1l

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53
Table 4 (Continued)
Entry
1a–m
CHO
3a–d
Product (4a–w)
Time (min)a
Yield (%)b
Cl
O
Cl
NH
O
O
22c
10
93
H3C
H3C
N
H
4v
O
1l
Cl
CHO
O
O
O
23c
10
94
H3CH2CO
NH
O
Cl
H3C
N
H
4w
O
1m
a
Reaction of different aldehydes (3 mmol), urea (4.5 mmol) and active methylene compounds (3/3.5 mmol) in presence of SSTA (200 mg) under solvent-free condition at
70 ◦C. Reaction progress was monitored by TLC. Compounds were purified by recrystallization from ethanol or DMSO.
b
Isolated yield.
c
Compounds characterized by their melting points, NMR spectra and comparing them with authentic samples.
C
O groups of tetrahydropyrimidine moiety merged into a broad
protons of two secondary amines. The proton of chromone moiety
showed a singlet at ı 7.37. The three protons of aromatic region
showed a multiplet in the range of ı 7.2–7.8 and the three protons
of methyl group showed a singlet at ı 3.36. 13C NMR also showed
peak at 1730 cm−1. The C O group of chromone moiety showed
absorption band at 1654 cm−1. The 1H NMR Spectrum showed two
distinctive singlets at ı 11.21 and ı 8.74 which were assigned to the
Fig. 5. (a) DSC analysis and (b) TG analysis of SSTA.
Scheme 2. Synthesis of different tetrahydropyrimidines (4a–l and dihydropyrimidinone derivatives 4m–w).

54
N. Ahmed, Z.N. Siddiqui / Journal of Molecular Catalysis A: Chemical 387 (2014) 45–56
Table 3
products (Table 4, entries 13–23). Moreover, aldehydes contained
both electron-with drawing and electron donating substituents
reacted very efficiently therefore, the effect of substituents was
not so marked. In order to show the efficiency of our catalyst it
was further compared with other reported catalysts in the lit-
erature like sulphated tungstate [32], PS–PEG–SO3H [33], silica
sulphuric acid [34], ␤-cyclodextrin [35], [Al(H2O)6](BF4)3 [36],
Fe3O4/PAA–SO3H [37], cellulose sulphuric acid [26], Cu(OTf)2 [38],
tetra-butyl ammonium bromide [39], and showed the superiority
of our catalyst in terms of reaction conditions, time and product
yield (Table 5).
Effect of different temperatures on the model reactiona.
Entry
Temp (◦C).
Timeb
Yieldc (%)
1
2
3
4
5
Room temp
–
–
45
94
92
87
40
7 h
70
80
100
15 min
15 min
15 min
a
Reaction of 6-methyl-3-formylchromone (1 mmol), urea (1.5 mmol) and ethyl
cyanoacetate (1 mmol) in presence of SSTA (200 mg) under solvent-free condition
at different temperatures.
b
Reaction progress monitored by TLC.
Isolated yield.
c
3.7. Reaction mechanism
distinctive peaks for C O group of chromone moiety at 180.22 and
A plausible mechanism for the formation of tetrahydropyrim-
idine 4a is depicted in Scheme 3. Probably, this transformation is
triggered by an initial activation of 3-formylchromone (1a) by pro-
tonation which then undergoes Knoevenagel condensation with
ethyl cyanoacetate (3a) forming alkene derivative (5a). This step is
followed by the addition of urea and elimination of ethoxy group.
Then intramolecular Michael addition followed by dehydrogena-
tion affords the product (4a). The catalyst is regenerated in the last
step and can be reused for six catalytic cycles [40].
C
O groups of tetrahydropyrimidine at 168.21 and 162.44 respec-
tively.
3.6.2. Catalytic activity of SSTA for Biginelli reaction
In order to further evaluate the catalytic activity of SSTA, we
explored this catalyst for the synthesis of dihydropyrimidinones
via Biginelli condensation of several aromatic and heterocyclic
aldehydes with 1,3-dicarbonyl compounds and urea under sim-
ilar reaction conditions. The reaction comprising benzaldehyde,
urea and ethylaceto acetate gave 96% product yield in only 10 min.
All substrates reacted efficiently and afforded high to excel-
lent yields of the corresponding dihydropyrimidinones within
short reaction times. Both ␤-ketoesters and ␤-diketones were
found to be equally active and provided excellent yields of the
4. Recyclability of the catalyst
Recyclability of the catalyst was evaluated by the reaction of
6-methyl-3-formylchromone (1b), ethylcyano acetate (3a) and
urea in the presence of SSTA under solvent-free conditions. After
Scheme 3. Plausible mechanism for the formation of tetrahydropyrimidine derivative by the reaction of 3-formylchromone, ethyl cyanoacetate and urea in presence of SSTA
under solvent-free conditions.

N. Ahmed, Z.N. Siddiqui / Journal of Molecular Catalysis A: Chemical 387 (2014) 45–56
55
Table 5
Effect of different reported catalysts for formation of dihydropyrimidines.
Entry
Catalyst
Condition
Yield (%)
Time
No. of recycles
1
2
3
4
5
6
7
8
9
SSTA
70 ◦C/solvent-free
80 ◦C/solvent free
80 ◦C/dioxane:2-propanol (4:3)
Reflux/ethanol
96
92
80
91
85
85
90
85
65
96
10 min
60 min
10 h
6 h
3 h
20 h
2 h
4.5 h
60 min
40 min
06
04
06
05
05
04
06
04
–
Sulphated tungstate
PS–PEG–SO3H
Silica sulphuric acid
␤-Cyclodextrin
[Al(H2O)6](BF4)3
Fe3O4/PAA-SO3H
Cellulose sulphuric acid
Cu(OTf)2
100 ◦C/solvent-free
Reflux/CH3CN
Room temp./solvent-free
100 ◦C/water
100 ◦C/ethanol
10
Tetra-butyl ammonium bromide
100 ◦C/KOH
–
Table 6
Appendix A. Supplementary data
Recycling data of SSTA for the model reactiona showing Concentrations of residual
H+ on the used support after successive experiments.
Supplementary material related to this article can be
found, in the online version, at http://dx.doi.org/10.1016/
j.molcata.2014.02.019.
Catalyst recycles
Timeb (min)
Yield (%)c
Conc. of residual H+ (mequiv/g)
1
2
3
4
5
6
15
15
15
15
15
15
94
94
94
92
91
89
0.40
0.40
0.35
0.35
0.30
0.25
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