Tungsten-substituted molybdophosphoric acid impregnated with kaolin: effective catalysts for the synthesis of 3,4-dihydropyrimidin-2(1: H)-ones v i a biginelli reaction

Article abstract of DOI:10.1039/d0ra09811f

A series of highly reusable heterogeneous catalysts (10-25 wt% PMo7W5/kaolin), consisting of tungsten-substituted molybdophosphoric acid, H3PMo7W5O40·24H2O (PMo7W5) impregnated with acid treated kaolin clay was synthesized by the wetness impregnation meth

Full text of DOI:10.1039/d0ra09811f

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Tungsten-substituted molybdophosphoric acid
impregnated with kaolin: effective catalysts for the
synthesis of 3,4-dihydropyrimidin-2(1H)-ones via
biginelli reaction†
Cite this: RSC Adv., 2021, 11, 2783
a
Dipak S. Aher,
Kiran R. Khillare,a Laxmikant D. Chavanb
a
*
and Sunil G. Shankarwar
A series of highly reusable heterogeneous catalysts (10–25 wt% PMo7W5/kaolin), consisting of tungsten-
substituted molybdophosphoric acid, H3PMo7W5O40$24H2O (PMo7W5) impregnated with acid treated
kaolin clay was synthesized by the wetness impregnation method. The newly synthesized catalyst was
fully characterized using inductively coupled plasma-atomic emission spectroscopy (ICP-AES), Fourier
transform infrared (FT-IR), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), energy
dispersive X-ray analysis (EDX), transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET)
analysis and thermal analysis (TG-DTA). The synthesized materials were shown to be efficient in the
synthesis of 3,4-dihydropyrimidin-2(1H)-ones via Biginelli reaction under solvent-free conditions. The
obtained results indicate that 20% PMo7W5/kaolin catalyst showed remarkably enhanced catalytic activity
compared to the bulk PMo7W5 catalyst, and also the (10 and 15%) PMo7W5 catalyst supported on kaolin clay.
Received 19th November 2020
Accepted 4th January 2021
DOI: 10.1039/d0ra09811f
rsc.li/rsc-advances
greater than that of molybdophosphoric acid (H3PMo12O40
-
1. Introduction
$nH2O). Therefore, it can be projected that replacement of
molybdenum (Mo) by tungsten (W) in the peripheral metal
atom positions of the anions can increase the acid strength of
the heteropoly acids, giving high catalytic activity for acid-
catalyzed reactions.18,19 Extremely low surface area, poor
stability and rapid deactivation are the major problems asso-
ciated with heteropoly acids.20 Hence, it is imperative to employ
an appropriate support to distribute the heteropoly acid.21–25
Kaolin, a clay mineral which is abundant on the earth, it is
composed of abundantly 1 : 1 clay mineral Al2Si2O5(OH)4
structure per alumina-silicate producing bulky congested
particles of SiO4 tetrahedral sheets and AlO2(OH)4 octahedral
sheets.26,27 Kaolin clay are promising supports due to their
common fascinating features, such as their inherent acidity,
excellent thermal stability and easily controlled structural
morphology.28 Therefore, the acidied-kaolin with larger
specic surface area is widely used as a very good catalyst
carrier.29 Actually, heteropoly acid-impregnated solid acids have
caused great interests in many elds.30,31
3,4-Dihydropyrimidin-2-(1H)-ones (DHPM) are of signicant
interest in industry as well as in academia because of their
promising biological and pharmacological activities such as
antitumor, antibacterial, antiviral and anti-inammatory activ-
ities.32,33 DHPM also have some other interesting pharmaco-
logical properties of being calcium channel modulators, anti-
HIV in some natural products containing the DHPM skeleton
and anti-cancer by inhibiting kinesin motor protein.34,35
Heteropoly acids (HPA) are well known as environmentally
benign and economically feasible alternatives to traditional
¨
acid catalysts due to their Bronsted acidity, high proton
mobility and relatively better stability.1–4 One of the important
structural subclass of HPAs is the Keggin anion, which is typi-
cally represented by the general formula XM12O40,xꢀ8 where X is
the central atom (Si, P, B, Zr etc.), x is its oxidation state, and M
is the metal ion (Mo6+or W6+).5–7 The M6+ ions can be replaced
by many other metal ions, e.g., V5+, Co2+, Zn2+, Ni2+ etc.8–12 The
Keggin anion is composed of a central tetrahedral XO4 sur-
rounded by 12 edge and corner sharing metal-oxygen octahedra
MO6. The octahedra are arranged in four M3O13 groups. Each
group is formed by three octahedra sharing edges and having
a mutual oxygen atom which is also shared with the central
tetrahedral XO4.13,14 The catalytic properties of Keggin type
heteropoly acids can be tuned by changing their central
heteroatoms, framework poly-atoms, and charge-compensating
cations because the substitution of these atoms changes their
acid and redox properties.15–17 It is well known that the acid
strength of tungstophosphoric acid (H3PW12O40$nH2O) is
aDepartment of Chemistry, Dr Babasaheb Ambedkar Marathwada University,
Aurangabad, 431 004, M.S., India. E-mail: shankarwar_chem@yahoo.com
bJawaharlal Nehru Engineering College, Aurangabad, 431003, M.S., India. E-mail:
chavan@rediffmail.com
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0ra09811f
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Scheme 1 Synthesis of tungsten-substituted molybdophosphoric acid, H3[PMo7W5O40]$24H2O.
Scheme 2 Preparation of the series of catalysts having 10–25% loading of H3[PMo7W5O40]$24H2O on kaolin clay support.
Therefore, development of new, efficient and convenient
protocols that lead to substituted DHPMs is of considerable
attention. This has led to the recent disclosure of several one-
2. Experimental section
2.1 Materials and general characterization
pot methodologies for the synthesis of DHPM derivatives such
as [bmim] [FeCl4],36 [bmim]BF4-immobilized Cu(II) acetylaceto-
nate,37 piperidinium triate38 and ammonium carbonate.39
However, some of existing methods associated with certain
limitations such as environmental pollution caused by utiliza-
tion of organic solvents, long reaction time, exotic reaction
conditions and expensive catalysts. Therefore, it is crucial to
further develop an efficient and convenient method to construct
such signicant scaffold (Scheme 1).
Encouraged by the intense ongoing research activity in the
eld of heterogeneous acid catalysis and in pursuit of our
continuous interest in the area of catalysis by supported het-
eropoly acids.40 Herein, we wish to report a simple, green and
efficient protocol for the synthesis of 3,4-dihydropyrimidin-
2(1H)-ones using series of tungsten-substituted molybdophos-
phoric acid (H3PMo7W5O40$24H2O) impregnated with kaolin
clay catalysts through Biginelli reaction (Scheme 2).
Disodium phosphate (Na2HPO4), Sodium molybdate (Na2-
MoO4$2H2O) sodium tungstate (Na2WO4$2H2O) and kaolin clay
(kaolin-product code: 15160) were purchased from MOLYCHEM
in India and used without further purication. All the chemicals
and solvents involved in the organic synthesis were purchased
from Merck, Sigma Aldrich and Alfa Aesar.
Element content was measured on an ARCOS, Simultaneous
ICP Spectrometer inductively coupled plasma atomic emission
spectroscopy (ICP-AES). The Fourier-transform infrared spec-
troscopy (FTIR) spectrum was performed on a Bruker ALPHA
(Eco-ATR) spectrophotometer. The materials were characterized
by X-ray powder diffraction (XRD) using a Bruker AXS Company,
D8 ADVANCE diffractometer (Germany). Scanning electron
microscopy (SEM) images were obtained using a FEI Nova
NanoSEM 450 combined with a Bruker XFlash 6I30 instrument
for energy-dispersive X-ray spectroscopy (EDX), with a scanning
electron electrode at 15 kV. Transmission electron microscopy
(TEM) images were collected using a (HR-TEM: Jeol/JEM 2100)
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operated at an accelerating voltage of 200 kV. Nitrogen ethanol (10 mL) and dried overnight for further reuse. The
adsorption–desorption isotherms were measured with a NOVA physical data (Melting point, IR and H1 & C13NMR) of known
Station A instrument at 77 K. The surface area calculated by the compounds (see S5†) were found to be identical with those re-
Brunauer–Emmett–Teller (BET) method and pore size distri- ported in the various literature.
bution derived from adsorption branches of the isotherms
using the distribution Barrett–Joyner–Halenda (BJH) method.
The thermal stability of the sample was carried out using
3. Result and discussion
simultaneous thermogravimetry (TG) and differential thermal
analysis (DTA) technique, measurements were performed using
a SHIMADZU, DTG-60H simultaneous DTA-TG apparatus. The
progress of the reaction monitored by thin-layer chromatog-
raphy on Merck's silica plates and imagining accomplished by
iodine/ultraviolet light. Melting points of all the synthesized
analogues were resolute in open capillary tube and are uncor-
rected. 1H and 13C NMR spectra were recorded on a Bruker
Avance 400 Spectrometer in DMSO and CDCl3. Chemical shis
are expressed in d parts per million relative to tetramethylsilane
(TMS) as the internal standard. All yields refer to the isolated
products.
3.1 Catalyst characterization
3.1.1 ICP-AES analysis. The results of ICP-AES elemental
analysis revealed that the atomic ratio of P/Mo/W is nearly
maintained 1.05 : 6.68 : 5.18 which corresponds to the formula
H3[PMo7W5O40]$24H2O (PMo7W5).18,40
3.1.2 FT-IR spectroscopy. Primarily, FT-IR spectroscopy
was used to conrm the successful functionalization of the
PMo7W5/kaolin catalyst (Fig. 1). For bulk PMo7W5, character-
istic bands exhibiting at 1061 (P–Oa in central tetrahedral), 960
(terminal M]Od), 873 (M–Ob–M), and 757 cmꢀ1 (M–Oc–M) are
accorded with asymmetric vibrations in Keggin unit.17 In the FT-
IR spectrum of kaolin, absorptions at 748 cmꢀ1 and 789 cmꢀ1
are attributed to Si–O–Al vibrations and the band at 915 cmꢀ1 is
assigned to Al-OH bending vibrations. The peak at 1007 cmꢀ1 is
assigned to Si–O–Si in-plane vibrations and at 1113 cmꢀ1 is
assigned to asymmetric Si–O–Si stretching vibrations.26 The
spectrum of PMo7W5/kaolin with different percentages of
PMo7W5 showed two bands at 938 and 910 cmꢀ1, which might
be attributed to the (terminal M]Od) and (M–Ob–M), respec-
tively. However, the bands at 1061 and 757 cmꢀ1 were not
prominent due to overlapping with the strong bands of silica in
the kaolin support.21
2.2 Catalyst preparation
2.2.1 Preparation of H3[PMo7W5O40]$24H2O (PMo7W5).
HPA with general formula H3[PMo7W5O40]$24H2O, was
synthesized using the procedure reported by Huixiong.18 Briey,
Disodium phosphate (0.63 g, Na2HPO4) and desired amount of
Sodium molybdate (7.48 g, Na2MoO4$2H2O) were dissolved in
distilled water. The obtained solution was stirred at 90 ꢁC. Aer
being stirred for 30 min, aqueous solution of sodium tungstate
(7.28 g, Na2WO4$2H2O) was added to the above heated solution.
Subsequently, sulfuric acid (H2SO4) solution was added drop
wise until the solution pH value reached about 1.5–2. The
resulting mixture was heated at 90 ꢁC for 6 h. Finally, the
solution was cooled and extracted with diethyl ether in sulfuric
acid environment. The powder H3[PMo7W5O40]$24H2O was
obtained aer concentrated etherate solution was dried in
vacuum.
3.1.3 XRD analysis. Fine dispersion of PMo7W5 on the
kaolin support was conrmed by XRD analysis. Fig. 2 shows the
2.2.2 Preparation
of
PMo7W5/kaolin.
PMo7W5
impregnated-kaolin catalysts were prepared according to liter-
ature procedures with small modications.21 In a typical
synthesis of 10% PMo7W5/kaolin, 0.5 g of PMo7W5 dissolved in
0.1 mol Lꢀ1 HCl solution was added into the ask containing
4.5 g of kaolin and stirred for 4 hours at room temperature. The
ꢁ
resulting mixture was heated to 80 C until complete evapora-
tion of the liquid part. Then solid residue calcined in an oven at
200 K for 5 h. A series of PMo7W5/kaolin (10, 15, 20, 25 wt%)
were prepared using the same method.
2.2.3 General procedure of the synthesis of 3,4-dihy-
dropyrimidin-2(1H)-ones. In a typical experiment, a mixture of
aromatic aldehyde (3 mmol), ethyl acetoacetate (3 mmol), urea
(3.2 mmol) and 20% PMo7W5/kaolin (0.1 g) was stirred at 80 ꢁC
under solvent-free conditions for suitable time as indicated by
thin-layer chromatography. Aer completion of reaction, the
reaction mixture was diluted using hot ethanol (10.0 mL) and
ltered for catalyst separation. The crude product was obtained
by solvent evaporation under reduced pressure and recrystal-
Fig. 1 FT-IR analysis of bulk PMo7W5, kaolin and PMo7W5/kaolin
lized from ethanol. The recovered catalyst was washed with composites.
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Table 1 Textural properties of the prepared catalyst
Entry Samples
SBET (m2 gꢀ1 Dpore (nm) Vpore (cm3 gꢀ1
) )
1
2
3
PMo7W5
Kaolin clay
20% PMo7W5/kaolin 6.199
5.3801
16.093
10.409
15.850
3.882
0.014
0.070
0.036
pattern as kaolin, indicating the retention of the original
characteristics of kaolin clay.42 The above results strongly
supports that PMo7W5 was nely and molecularly dispersed on
the kaolin support in the PMo7W5/kaolin catalyst.28,43
3.1.4 SEM and TEM analysis. The surface morphology and
texture of produced samples was investigated using SEM and
TEM analysis (Fig. 3a–d). As seen in Fig. 3a, the irregularly
shaped particles with rough, aky edges were observed for bulk
PMo7W5 sample. The SEM images of kaolin and 20% PMo7W5/
kaolin are shown in Fig. 3b and c respectively. These images
clearly show that the surface morphology of supported catalyst
is almost identical to that of pure kaolin. No change in surface
morphology of the catalyst demonstrate that PMo7W5 species
are well dispersed inside the hexagonal pores.41 Further, no
separate crystallites of bulk phase of PMo7W5 were found in
20% PMo7W5/Kaolin.
Fig. 2 XRD patterns of bulk PMo7W5, kaolin and PMo7W5/kaolin
composites.
The TEM images of 20% PMo7W5/kaolin (Fig. 3d) shows that
most of the hexagonal pores covered with dark colored ne
particles. This indicates uniform dispersion of PMo7W5 inside
the hexagonal pores of kaolin clay support.
3.1.5 EDX analysis and mapping images. The chemical
constitution of bulk PMo7W5 and 20% PMo7W5/kaolin were
evidenced by EDX analysis as depicted in Fig. S2.† The results of
newly prepared PMo7W5 conrms the presence of P, Mo and W
(Fig. S1-a†). Moreover, the EDX results of 20% PMo7W5/kaolin
(Fig. S2-b†) showed the presence of P, Mo and W elements of
PMo7 W5 and Si, Al and O of kaolin clay. Which strongly indi-
cates the successfully formation of 20% PMo7W5/kaolin.42
Additionally, EDS mapping images proved a uniform distri-
bution of W, Mo and P in the desired PMo7W5 catalyst system
(Fig. 4a). The elemental mapping of Fig. 4b depicted the
construction of a well-dispersed composite material of P,
Mo, W, Si, Al and O in the synthesized 20% PMo7W5/kaolin
catalyst, which is in moral contract with FT-IR, XRD and SEM
results.
Fig. 3 FE-SEM images of bulk PMo7W5 (a), kaolin (b), 20% PMo7W5/
kaolin (c) and TEM images of 20% PMo7W5/kaolin (d).
3.1.6 BET analysis. The specic surface area is an impor-
tant representative of a catalyst. The specic surface area, pore
diameter, and pore volume of the catalysts were determined by
BET and BJH methods. The specic surface area of the PMo7W5,
kaolin support and 20% PMo7W5/kaolin catalysts were 5.3801,
16.093 and 6.199 m2 gꢀ1, respectively (Table 1). The porosities of
these catalysts was investigated by N2 adsorption/desorption
measurement. N2 adsorption/desorption isotherm are the type
IV in nature according to the IUPAC classication. The bulk
PMo7W5 exhibit a well expressed H4 hysteresis loop (Fig. 5a),
whereas, parent kaolin clay and 20% PMo7W5/kaolin catalyst
exhibit H3 hysteresis loop (Fig. 5b and c) in the range of 0.4–1.0
P/P0 at high relative pressure, which is typical for mesoporous
XRD patterns of PMo7W5, kaolin support and PMo7W5/kaolin
composites (with PMo7W5 loading from 10, 15, 20 and 25%).
Unsupported PMo7W5 showed the characteristic XRD peaks of
the Keggin structure mainly exist in four ranges of 2q ¼ 7–10ꢁ,
18–23ꢁ, 25–30ꢁ and 31–37ꢁ (ref. 17) On the other hand, several
prominent peaks of kaolin detected at about 2q ¼ 12.36ꢁ,
20.44ꢁ, 21.42ꢁ, 25.10ꢁ, 35.03ꢁ, 38.48ꢁ and 62.38ꢁ. The peak at 2q
¼ 12.36ꢁ is the distinctive XRD form of kaolin.41 Interestingly,
10, 15, 20 and 25% PMo7W5/kaolin catalyst exhibited no char-
acteristic peaks of PMo7W5 but showed almost the same XRD
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Fig. 4 Elemental mapping images of (a) bulk PMo7W5 (b) 20% PMo7W5/kaolin catalyst.
The study proven that the surface area of 20% PMo7W5/
kaolin catalyst slightly increased but not more than that of
kaolin support.46 This could primarily due to deposition and
incorporation of PMo7W5 catalyst into the pores of kaolin
support.47
3.1.7 TG-DT analysis. The thermal stability of bulk PMo7W5
and 20% PMo7W5/kaolin examined by the thermogravimetric
(TG) and differential thermal analysis (DTA). The hydrated
solids usually obtained with a large amount of water of crys-
tallization. Generally, three types of crystallographic water
molecule could be distinguishes in the hydrated solid
(Fig. 6a).48,49 The TG curve for bulk PMo7W5 shows the total
weight loss of 16.01% below 460 ꢁC indicating that 24 water
molecules calculated were lost. The rst mass loss stage, free
Fig. 5 N2 adsorption–desorption isotherms of (a) PMo7W5 (b) kaolin
support (c) 20% PMo7W5/kaolin.
materials. As demonstrated in Table 1, the pore diameter of the
PMo7W5, kaolin support and 20% PMo7W5/kaolin catalyst were
10.409, 15.850, and 3.882 nm respectively. Also pore volume
(0.014–0.070 cm3 gꢀ1) of the catalysts were calculated using the
BJH method (see Fig. S3-a–c†).26,44,45
Scheme 3 Synthesis of ethyl 6-methyl-2-oxo-4-aryl-1,2,3,4-tetra-
hydropyrimidine-5-carboxylate (4a–n) by using 20% PMo7W5/kaolin
catalyst.
Fig. 6 TG-DT analysis of (a) PMo7W5 and (b) 20% PMo7W5/kaolin catalyst.
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Table 2 Effect of H3PMo7W5O40$24H2O loading on support kaolin for Table 4 Effect of different solvents on the ethyl 6-methyl-2-oxo-4-
the synthesis of ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahy- phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4a)a
dropyrimidine-5-carboxylate (4a)a
Entry Catalyst (mg) Temp. ꢁC Solvent
Timeb
Yieldc (%)
Entry
Catalyst
Timeb (min)
Yieldc (%)
1
2
3
4
5
6
7
100
100
100
100
100
100
100
Reux
Reux
Reux
Reux
80
EtOH
H2O
MeOH
CH3CN
DMF
15 min 72
10 min 68
25 min 62
45 min 45
65 min 55
30 min 59
1
2
Pure kaolin
Bulk
120
55
45
60
H3PMo7W5O40$24H2O
10% PMo7W5/kaolin
15% PMo7W5/kaolin
20% PMo7W5/kaolin
25% PMo7W5/kaolin
3
4
5
6
35
20
08
08
68
85
95
95
Reux
80
CH2Cl2
Solvent-free 8 min
95
a
Reaction conditions: benzaldehyde (3 mmol), ethyl acetoacetate (3
b
a
mmol), urea (3.2 mmol) and 20% PMo7W5/kaolin catalyst. Reaction
Reaction conditions: benzaldehyde (3 mmol), ethyl acetoacetate (3
progress monitored by TLC. c Isolated yields.
b
mmol), urea (3.2 mmol) and PMo7W5/kaolin catalyst. Reaction
progress monitored by TLC. c Isolated yields.
aryl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
derivatives.
Benzaldehyde (3 mmol), ethyl acetoacetate (3 mmol) and urea
(3.2 mmol) were chosen as substrates for model reaction
(Scheme 3).
Table 3 Effect of temperature and amount of catalyst on ethyl 6-
methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4a)a
Entry
Catalyst (mg)
Temp. ꢁ
C
Timeb
Yieldc (%)
Table 5 Synthesis of ethyl 6-methyl-2-oxo-4-aryl-1,2,3,4-tetrahy-
dropyrimidine-5-carboxylate (4a–n) by using 20% PMo7W5/kaolin
catalysta,b
1
2
3
4
5
6
7
8
0
25
50
80
80
80
80
80
80
70
60
24 h
Trace
65
70
82
95
95
65
45
8 min
8 min
8 min
8 min
8 min
8 min
8 min
70
100
125
100
100
a
Reaction conditions: benzaldehyde (3 mmol), ethyl acetoacetate (3
b
mmol), urea (3.2 mmol) and 20% PMo7W5/kaolin catalyst. Reaction
progress monitored by TLC. c Isolated yields.
crystalized water, 10.20% of the total sample mass was lost and
ꢁ
an endothermic peak appeared at 95 C for 15-water molecule.
The second mass lost for H+ -combined water, about 3.27% of
the total sample mass was loss and endothermic peak appeared
ꢁ
at 147 C for 4.9 water molecule. The structure water, 2.5% of
the total sample mass loss and DTA curve shows the exothermic
peak at 467 ꢁC, which demonstrate stability of Keggin unit and
these third mass losses for oxide mixture.
The TG-DTA of supported PMo7W5 on kaolin showed the
mass loss of about 3.51% up to 430 ꢁC temperature corresponds
to dehydration of surface and interlayer water molecules
(Fig. 6b). The gradual mass loss about 7.19% within the
temperature range 430 ꢁC to 750 ꢁC, which indicates an increase
in the thermal stability of bulk PMo7W5 on kaolin clay
support.40 This might be due to formation of intermolecular
bonding interaction between kaolin and bulk PMo7W5. The
above result reveals that strong chemical interaction between
kaolin and PMo7W5 catalyst.
3.2 Catalytic activity
a
Reaction conditions: aldehydes (4a–n) (3 mmol), ethyl acetoacetate (3
Our initial studies were focused on the optimization of the
reaction conditions for the synthesis of ethyl 6-methyl-2-oxo-4-
mmol), and urea (3.2 mmol) in 20% PMo7W5/kaolin (0.1 g) stirred at
80 ꢁC. b Isolated yields.
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Table 6 Biginelli reaction of benzaldehyde, ethyl acetoacetate and urea with different catalystsa
Entry
Catalyst
Condition
Time
Yieldb (%) Ref
1
2
3
4
5
6
7
8
p-Sulfonic acid calixarenes
NH4H2PO4/MCM-41
[Et3NH] [HSO4]
12-Tungstophosphoric acid
[Btto][p-TSA]
Fe3O4/PAA-SO3H
SnCl2/nano SiO2
Bentonite/PS-SO3H
Fe3O4@SBA-15
PS-PEG-SO3H
EtOH, reux
8 h
6 h
1 h
6 h
30 min
2 h
40 min
30 min
6 h
69 (ref. 50
72 (ref. 51
75 (ref. 52
98 (ref. 53
96 (ref. 54
90 (ref. 55
94 (ref. 56
89 (ref. 57
85 (ref. 58
80 (ref. 59
)
)
)
)
)
)
)
)
)
)
Solvent-free, 100 ꢁ
Solvent-free, 100 ꢁ
Reux, acetic acid
C
C
Solvent-free, 90 ꢁC
Solvent-free, rt
EtOH, reux
Solvent-free, 120 ꢁ
C
9
10
11
EtOH, 90 ꢁ
Dioxane & 2-propanol, 80 ꢁC
Solvent-free, 80 ꢁ
C
10 h
8 min
20% PMo7W5/kaolin
C
95 (this work)
a
Reaction conditions: benzaldehydes (3 mmol), ethyl acetoacetate (3 mmol), and urea (3.2 mmol) in 20% PMo7W5/kaolin (0.1 g) stirred at 80 ꢁC.
Isolated yields.
b
Table 7 Recycling and reuse of the catalysta
3, 4, and 5). Further, an increase in PMo7W5 catalyst loading
above 20% w/w on kaolin support have no effect on yield of
product and reaction time due to leaching of catalyst from the
support (Table 2, entry 6). The increase in activity of the 20%
PMo7W5/kaolin catalyst was due to high dispersion of PMo7W5
catalyst on kaolin support. This would lead to an increase in its
surface area and the number of active sites compared with the
bulk PMo7W5 catalyst. Hence, 20% PMo7W5/kaolin catalyst was
found to be optimal amount and adequate to push the reaction
forward.
Entry
Number of recycle
Yield (%)b
1
2
3
4
5
6
1
2
3
4
5
6
95
95
94
90
90
88
a
Reaction conditions: benzaldehyde (3 mmol), ethyl acetoacetate (3
mmol), urea (3.2 mmol) and 20% PMo7W5/kaolin catalyst, time 8 min.
Isolated yields.
b
The determination of appropriate amount of the catalyst for
catalyzing the reaction is another critical parameter in terms of
reaction efficiency. To nd appropriate amount of catalyst, the
model reaction was carried out in the presence of different
amounts (25, 50, 70, 100 and 125 mg) of 20% PMo7W5/kaolin
and obtained results are summarized in Table 3. When the
amount of 20% PMo7W5/kaolin increases gradually, product
yield also increases (Table 3, entries 1–5). The obtained results
demonstrates that 100 mg amount of 20% PMo7W5/kaolin
Various amounts of PMo7W5/kaolin were used to study the
effect of the composition of the catalyst on the conversion and
obtained results are summarized in Table 2. Pure kaolin showed
extremely low catalytic activity in terms of the reaction time and
the yield of the desired product (Table 2, entry 1). Bulk PMo7W5
gave a moderate yield of the product but only aer an extended
reaction time (Table 2, entry 2). It was observed that both yield
of the product and reaction time were improved upon
increasing the catalyst loading up to 20% w/w (Table 2, entries
ꢁ
catalyst gave 95% yield of product at 80 C (Table 3, entry 5).
Additional increase in the amount (125 mg) of 20% PMo7W5/
kaolin does not increase in the yield of the product (Table 3,
entry 5). This may be due to overtiredness of the catalytic site or
Fig. 7 FT-IR (a) and XRD (b) analysis of recovered 20% PMo7W5/kaolin catalyst.
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organic solvents (Table 4). Initially, the model reaction was
carried out in ethanol and water at reux temperature the
moderate yield were obtained (Table 4, entries 1, 2). When the
methanol, acetonitrile, dichloromethane were used as solvent
ꢁ
at reux temperature and DMF at 80 C, it gave lower yields of
product (Table 4, entries 3–6). None of the above solvents
demonstrates the advantage of time and yield instead of
solvent-free condition (Table 4, entry 7). Therefore, solvent-free
condition was superior in terms of cost and it is environmen-
tally benign to promote further derivatives (Table 5).
A comparative study was performed for the use of 20%
PMo7W5/kaolin with some of the reported catalysts for the
synthesis of 6-methyl-2-oxo-4-aryl-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (Table 6). Reaction with different catalysts
required a higher amount of catalyst and longer reaction times
compared with 20% PMo7W5/kaolin in solvent-free systems. In
most methods, the reaction was achieved in solvent such as
ethanol, acetic acid and dioxane. Thus, 20% PMo7W5/kaolin
encouraged the reactions more effectively than the other cata-
lysts and should be considered as one of the top choices for
selecting an economically convenient, user-friendly catalyst.
Fig. 8 Recyclability test of 20% PMo7W5/kaolin catalyst on model
reaction.
accomplishment of the maximum conversion efficiency of the
catalyst. It is also important to note that at 60 and 70 ꢁC low to
moderate conversion observed, whereas at 80 ꢁC excellent
conversion of starting material were seen (Table 3, entry 5 versus
entries 7 and 8). The effectiveness of model reaction also
studied without using any catalyst. Where, trace amount of the
product obtained aer a long period (Table 3, entry 1).
3.3 Recycling of the catalyst
Further, the efficiency of 20% PMo7W5/kaolin was investi-
gated by using 100 mg of 20% PMo7W5/kaolin in various
One of the most important features of the present methodology
is the recyclability of the catalyst. It was observed that the 20%
Scheme 4 Proposed mechanism for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones.
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PMo7W5/kaolin catalyst could be reused multiple times. For this
purpose, the same model reaction was performed again studied
under the optimized conditions (Table 7). Aer reaction
completion, the reaction mixture was diluted using hot ethanol
and ltered for catalyst separation, the solid catalyst was
washed with ethanol several times, dried and calcined at 200 ꢁC
for 5 h and reused for subsequent reaction. The results (Fig. 8)
revealed that the catalyst exhibited good catalytic activity up to
six consecutive cycles.
The FT-IR and XRD spectra of the recovered 20% PMo7W5/
kaolin (aer six cycles) were matched with those of the fresh
sample. As documented in Fig. 7, the FT-IR showed two bands
at 938 and 910 cmꢀ1 were found to similar of fresh 20%
PMo7W5/kaolin (Fig. 7a verses Fig. 1). XRD spectra displayed by
the recovered 20% PMo7W5/kaolin catalyst at 2q ¼ 20.12ꢁ,
21.97ꢁ, 23.65, 25.63ꢁ, 35.53ꢁ and 59.32ꢁ were found to be almost
similar to the fresh one (Fig. 7b verses Fig. 2).
Acknowledgements
The author DSA is gratefully acknowledges the University Grant
Commission (UGC), New Delhi (India) for senior research
fellowship (SRF). SGS is thankful to Dr Babasaheb Ambedkar
Marathwada University, Aurangabad (MS), India (STAT/VI/RG/
DEPT/2019-20/337-38) and UGC-DST SAP for nancial assis-
tance. We are also thankful to Department of Chemistry, Dr
Babasaheb Ambedkar Marathwada University, Aurangabad
(MS), India for providing laboratory facility.
Notes and references
1 H. R. Gurav, K. Y. Nandiwale and V. V. Bokade, J. Phys. Org.
Chem., 2014, 27, 121–127.
2 R. Chen, J. Xin, D. Yan, H. Dong, X. Lu and S. Zhang,
ChemSusChem, 2019, 12, 2715–2724.
3 J. L. Horan, A. Genupur, H. Ren, B. J. Sikora, M.-C. Kuo,
F. Meng, S. F. Dec, G. M. Haugen, M. A. Yandrasits,
S. J. Hamrock, M. H. Frey and A. M. Herring,
ChemSusChem, 2009, 2, 226–229.
4 J. Li, X. Wang, W. Zhu and F. Cao, ChemSusChem, 2009, 2,
177–183.
5 N. L. Mulik, P. S. Niphadkar, K. V. Pandhare and
V. V. Bokade, ChemistrySelect, 2018, 3, 832–836.
6 R. Chaudhary and M. Datta, J. Anal. Sci., Methods Instrum.,
2013, 03, 193–201.
7 M. M. Heravi, M. Mirzaei, S. Y. S. Beheshtiha, V. Zadsirjan,
F. Mashayekh Ameli and M. Bazargan, Appl. Organomet.
Chem., 2018, 32, 1–10.
3.4 Plausible reaction mechanism
The possible reaction pathway for the Biginelli three-
component condensation mediated by 20%PMo7W5/kaolin
was depicted in Scheme 4. The rst step involves nucleophilic
attack of urea (3) on the electron decient carbon of aldehyde
(1). Here, electrophilicity of carbonyl group of aldehyde
¨
increased due to Bronsted and Lewis acidic nature of 20%
PMo7W5/kaolin, which leads to formation of N-acyliminium ion
intermediate (a). Interception of this iminium ion intermediate
by activated 1,3-dicarbonyl compound (2) produces an open-
chain ureide (b) which subsequently undergoes cyclization
and
dehydration
to
afford
the
corresponding
dihydropyrimidinones.
8 E. G. Zhizhina, Y. A. Rodikova, O. Y. Podyacheva and
Z. P. Pai, Z. Anorg. Allg. Chem., 2018, 644, 869–876.
9 N. C. Coronel, M. J. da Silva, S. O. Ferreira, R. C. da Silva and
R. Natalino, ChemistrySelect, 2019, 4, 302–310.
10 W.-S. Che, H.-H. Gai, W.-B. Hao and R.-H. Ma, Synth. React.
Inorg., Met.-Org., Synth. React. Inorg., Met.-Org., Nano-Met.
Chem., 2014, 44, 649–655.
4. Conclusion
In conclusion, we have successfully synthesis a series of
tungsten-substituted molybdophosphoric acid (H3PMo7W5O40
-
$24H2O) catalyst impregnated with acidied kaolin clay. The
catalytic activity of PMo7W5/kaolin was probed through one-pot
synthesis of 3,4-dihydropyrimidin-2(1H)-ones via Biginelli
reaction. The 20% PMo7W5/kaolin showed higher catalytic
activity than the bulk PMo7W5 catalyst, as well as the 10% and
15% PMo7W5/kaolin. The effects of various parameters such as
catalyst loading, amount of catalyst, effect of solvents, inuence
of temperature on the rate of reaction, comparison of different
catalyst was discussed in detail. The 20% PMo7W5/kaolin cata-
lyst shows very high conversion rates in short reaction times.
This catalyst was recovered easily from reaction mixture and
reused at least six times without signicant loss of its catalytic
activity. Therefore, the newly synthesised 20% PMo7W5/kaolin
could be used as a promising heterogeneous catalyst for a wide
range of multifunctional applications.
11 S. Bencedira, O. Bechiri, M. Djenouhat and M. Boulkra,
Arabian J. Sci. Eng., 2020, 45, 4669–4681.
12 S. Tang, W. Wu, Z. Fu, S. Zou, Y. Liu, H. Zhao, S. R. Kirk and
D. Yin, ChemCatChem, 2015, 7, 2637–2645.
13 C. L. Hill and C. M. Prosser-McCartha, Coord. Chem. Rev.,
1995, 143, 407–455.
14 J. Xu, R. W. Gable and C. Ritchie, Acta Crystallogr., 2018, 74,
1384–1389.
15 M. Chamack, A. R. Mahjoub and H. Aghayan, Chem. Eng. J.,
2014, 255, 686–694.
16 H. Fakhri, A. R. Mahjoub and H. Aghayan, J. Radioanal. Nucl.
Chem., 2019, 321, 449–461.
17 H. Aghayan, A. R. Khanchi, T. Youse and H. Ghasemi, J.
Nucl. Mater., 2017, 496, 207–214.
18 H. Wu, M. Zhou, Y. Qu, H. Li and H. Yin, Chin. J. Chem. Eng.,
2009, 17, 200–206.
19 I. V. Kozhevnikov, Chem. Rev., 1998, 98, 171–198.
20 A. D. Newman, D. R. Brown, P. Siril, A. F. Lee and K. Wilson,
Phys. Chem. Chem. Phys., 2006, 8, 2893.
Conflicts of interest
There are no conicts to declare.
© 2021 The Author(s). Published by the Royal Society of Chemistry
RSC Adv., 2021, 11, 2783–2792 | 2791

View Article Online
RSC Advances
Paper
21 L. H. O. Pires, A. N. de Oliveira, N. Alex Jr, R. S. Angelica, 40 D. S. Aher, K. R. Khillare, L. D. Chavan and S. G. Shankarwar,
C. E. F. da Costa, J. R. Zamian, L. A. S. do Nascimento and
G. N. R. Filho, Appl. Catal., B, 2014, 160–161, 122–128.
22 T. Suppan, M. K. Kunjunni, A. Barik and R. R. Bhattacharjee,
ChemistrySelect, 2018, 3, 1275–1281.
ChemistrySelect, 2020, 5, 7320–7331.
41 O. D. S. Lacerda, R. M. Cavalcanti, T. M. de Matos,
´
R. S. Angelica, G. N. da Rocha Filho and I. D. C. L. Barros,
Fuel, 2013, 108, 604–611.
23 L. Muraleedharan, Bellundagere, M. Chandrashekara, 42 L. V. Chopda and P. N. Dave, ChemistrySelect, 2020, 5, 2395–
Bangalore, S. J. Prakash, Yajnavalkya and S. Bhat,
ChemistrySelect, 2018, 3, 801–808.
24 A. E. R. S. Khder, H. M. A. Hassan and M. S. El-Shall, Appl.
Catal., A, 2012, 411–412, 77–86.
25 D. S. Park, B. K. Kwak, N. D. Kim, J. R. Park, J. H. Cho, S. Oh
and J. Yi, ChemCatChem, 2012, 4, 836–843.
26 A. G. Olaremu, J. Miner. Mater. Charact. Eng., 2015, 03, 353–
361.
27 S. Yahaya, S. S. Jikan, N. A. Badarulzaman and A. D. Adamu,
Path Sci., 2017, 3, 1001–1004.
2400.
43 D. S. Aher, K. R. Khillare, L. D. Chavan and S. G. Shankarwar,
ChemistrySelect, 2020, 5, 7320–7331.
44 L. Rozic, B. Grbic, S. Petrovic, N. Radic, L. Damjanovic and
Z. Vukovic, Mater. Chem. Phys., 2015, 167, 42–48.
45 A. B. Gawade, M. S. Tiwari and G. D. Yadav, ACS Sustainable
Chem. Eng., 2016, 4, 4113–4123.
46 V. V. Bokade and G. D. Yadav, Appl. Clay Sci., 2011, 53, 263–
271.
47 G. Yadav, J. Catal., 2003, 217, 88–99.
28 S. Attique, M. Batool, M. I. Jalees, K. Shehzad, U. Farooq, 48 Z. Xie, H. Wu, Q. Wu and L. Ai, RSC Adv., 2018, 8, 13984–
Z. Khan, F. Ashraf and A. T. Shah, Turk. J. Chem., 2018, 42,
684–693.
13988.
49 H. Cai, X. Wu, Q. Wu and W. Yan, Dalton Trans., 2016, 45,
14238–14242.
´
29 J. P. Nguetnkam, R. Kamga, F. Villieras, G. E. Ekodeck,
A. Razatianamaharavo and J. Yvon, J. Colloid Interface 50 D. L. Da Silva, S. A. Fernandes, A. A. Sabino and A. De Fa,
Sci., 2005, 289, 104–115. Tetrahedron Lett., 2011, 52, 6328–6330.
30 S. K. Kundu, J. Mondal and A. Bhaumik, Dalton Trans., 2013, 51 R. Tayebee and M. Ghadamgahi, Arabian J. Chem., 2017, 10,
42, 10515–10524. S757–S764.
31 L. Chen, B. Nohair, D. Zhao and S. Kaliaguine, 52 H. Khabazzadeh, E. T. Kermani and T. Jazinizadeh, Arabian
ChemCatChem, 2018, 10, 1918–1925. J. Chem., 2012, 5, 485–488.
32 K. S. Atwal, B. N. Swanson, S. E. Unger, D. M. Floyd, 53 M. M. Heravi, F. Derikvand and F. F. Bamoharram, J. Mol.
S. Moreland, A. Hedberg and B. C. O'Reilly, J. Med. Chem.,
1991, 34, 806–811.
33 J. Azizian, M. K. Mohammadi, O. Firuzi, B. Mirza and R. Miri,
Chem. Biol. Drug Des., 2010, 75, 375–380.
Catal. A: Chem., 2005, 242, 173–175.
54 Y. Zhang, B. Wang, X. Zhang, J. Huang and C. Liu, Molecules,
2015, 20, 3811–3820.
55 F. Zamani and E. Izadi, Catal. Commun., 2013, 42, 104–108.
34 A. T. Khan, M. Lal, S. Ali and M. M. Khan, Tetrahedron Lett., 56 J. Safaei Ghomi, R. Teymuri and A. Ziarati, Monatsh. Chem.,
2011, 52, 5327–5332.
2013, 144, 1865–1870.
35 C. O. Kappe, Eur. J. Med. Chem., 2000, 35, 1043–1052.
36 X. Chen and Y. Peng, Catal. Lett., 2008, 122, 310–313.
57 R. J. Kalbasi, A. R. Massah and B. Daneshvarnejad, Appl. Clay
Sci., 2012, 55, 1–9.
37 S. L. Jain, J. K. Joseph and B. Sain, Catal. Lett., 2007, 115, 52– 58 J. Mondal, T. Sen and A. Bhaumik, Dalton Trans., 2012, 41,
55. 6173.
38 C. Ramalingan, S. J. Park, I. S. Lee and Y. W. Kwak, 59 Z.-J. Quan, Y.-X. Da, Z. Zhang and X.-C. Wang, Catal.
Tetrahedron, 2010, 66, 2987–2994.
39 F. Tamaddon, Z. Razmi and A. A. Jafari, Tetrahedron Lett.,
2010, 51, 1187–1189.
Commun., 2009, 10, 1146–1148.
2792 | RSC Adv., 2021, 11, 2783–2792
© 2021 The Author(s). Published by the Royal Society of Chemistry