Nanometasilica disulfuric acid (NMSDSA) and nanometasilica monosulfuric acid sodium salt (NMSMSA) as two novel nanostructured catalysts: applications in the synthesis of Biginelli-type, polyhydroquinoline and 2,3-dihydroquinazolin-4(1H)-one derivatives

Article abstract of DOI:10.1007/s13738-016-0964-1

Abstract: Nanometasilica disulfuric acid (NMSDSA) and nanometasilica monosulfuric acid sodium salt (NMSMSA) as two nanostructured novel, green and heterogeneous catalysts were designed, synthesized and fully characterized by FT-IR, energy-dispersive X-ray spectroscopy, X-ray diffraction patterns, scanning electron microscopy, transmission electron microscopy and thermal gravimetric analysis. Then their catalytic applications were studied in the Biginelli-type reaction for the synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives via one-pot three-component condensation reaction between several aldehydes, ethyl acetoacetate and urea or thiourea. To further study catalytic properties of NMSDSA and NMSMSA, they were used in the synthesis of polyhydroquinoline and 2,3-dihydroquinazolin-4(1H)-one derivatives under same reaction conditions. NMSDSA and NMSMSA have advantages such as cost-effectiveness, cleaner reaction profile, benign and heterogeneous characters, reusability of the catalysts and being in agreement with the green chemistry protocols. The described nanostructured catalysts have natural-based acids and potential for industrial production. Graphical Abstract: Synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives via Biginelli-type reaction, polyhydroquinolines and 2,3-dihydroquinazolin-4(1H)-ones using NMSDSA and NMSMSA as two novel nanostructured catalysts. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s13738-016-0964-1

J IRAN CHEM SOC
DOI 10.1007/s13738-016-0964-1
ORIGINAL PAPER
Nanometasilica disulfuric acid (NMSDSA) and nanometasilica
monosulfuric acid sodium salt (NMSMSA) as two
novel nanostructured catalysts: applications in the
synthesis of Biginelli‑type, polyhydroquinoline
and 2,3‑dihydroquinazolin‑4(1H)‑one derivatives
Mohammad Ali Zolfigol1 · Hossein Ghaderi1 · Saeed Baghery1 · Leila Mohammadi1
Received: 14 May 2016 / Accepted: 11 August 2016
© Iranian Chemical Society 2016
Abstract Nanometasilica disulfuric acid (NMSDSA) and
nanometasilica monosulfuric acid sodium salt (NMS-
MSA) as two nanostructured novel, green and heterogene-
ous catalysts were designed, synthesized and fully char-
acterized by FT-IR, energy-dispersive X-ray spectroscopy,
X-ray diffraction patterns, scanning electron microscopy,
transmission electron microscopy and thermal gravimetric
analysis. Then their catalytic applications were studied in
the Biginelli-type reaction for the synthesis of 3,4-dihy-
dropyrimidin-2(1H)-one derivatives via one-pot three-
component condensation reaction between several alde-
hydes, ethyl acetoacetate and urea or thiourea. To further
study catalytic properties of NMSDSA and NMSMSA,
they were used in the synthesis of polyhydroquinoline
and 2,3-dihydroquinazolin-4(1H)-one derivatives under
same reaction conditions. NMSDSA and NMSMSA have
advantages such as cost-effectiveness, cleaner reaction
profile, benign and heterogeneous characters, reusability
of the catalysts and being in agreement with the green
chemistry protocols. The described nanostructured cata-
lysts have natural-based acids and potential for industrial
production.
polyhydroquinolines and 2,3-dihydroquinazolin-4(1H)-
ones using NMSDSA and NMSMSA as two novel nano-
structured catalysts.
O
O
O
Cat (10 mol%)
Solvent-free, 80 oC
S
Si
O
Na
O
O
O
O
O
O
H
O
S
Si
S
Nanometasilica mono sulfuric
O
O
H
H
O
O
acid sodium salt
Nanometasilica disulfuric acid
(NMSDSA)
(NMSMSA)
CHO
O
O
R
or
+
O
O
R
1
2
O
NH
X
=
or
X
O
S
4
N
H
X
H2N
NH2
3
O
R
R'
R'
O
O
O
5
CHO
O
OR''
+
R'
R'
7
2
N
H
R''O
O
R
1
NH4OAc
Graphical Abstract Synthesis of 3,4-dihydropyrimi-
din-2(1H)-one derivatives via Biginelli-type reaction,
6
O
O
CHO
R
NH
9
NH2
NH2
R
+
N
H
8
1
Keywords Nanometasilica disulfuric acid
(NMSDSA) · Nanometasilica monosulfuric acid
sodium salt (NMSMSA) · Biginelli-type reaction ·
* Mohammad Ali Zolfigol
zolfi@basu.ac.ir; mzolfigol@yahoo.com
1
3,4-Dihydropyrimidin-2(1H)-one · Polyhydroquinoline ·
2,3-Dihydroquinazolin-4(1H)-one · Solvent-free
Department of Organic Chemistry, Faculty of Chemistry, Bu-
Ali Sina University, Hamedan 6517838683, Iran
1 3

J IRAN CHEM SOC
sodium metasilicate reacts with one or two equivalents of
chlorosulfonic acid to synthesize nanometasilica mono-
sulfuric acid sodium salt (NMSMSA) and nanometasilica
disulfuric acid (NMSDSA), respectively. It is fascinating to
note that the reaction is simple and safe without any work-
up process because NaCl salt is performed as a solely by-
product (Scheme 1).
Introduction
Knowledge-based developments of task-specific and nat-
ural-based catalysts are more demanded because catalytic
systems have played an excellent role in the pollution pre-
vention in our environment [1]. In this regard, a wide range
of catalysts and their supported heterogeneous forms are
reported in the last few years for various chemical and bio-
chemical processes and extensively have been reviewed.
Among the reported solid catalysts, solid inorganic and
natural-based acids have been also used widely for various
organic functional group transformations [2]. The outstand-
ing potential and environmentally benign properties of sil-
ica make it the best choice, either as major support (core)
or as coating agent for the synthesis of a wide variety of
heterogeneous catalysts [3, 4]. One of the most important
strategies to combine economic aspects with the environ-
mental concerns is the use of silica or its corresponding
derivatives as a core or coating agent in the synthesis of
porous materials and nanocatalysts [5]. Silica sulfuric acid
(SSA) as a familiar example has been prepared via reac-
tion between silica gel and chlorosulfonic acid at room
temperature [6]. SSA and its different forms as a superior
proton source of all of the reported acidic solid supports or
acidic resins have been widely used for a various functional
groups transformations [7–10] and extensively reviewed
[11].
The Biginelli-type reaction, as a significant and valuable
MCRs, offers an efficient technique to give multi-function-
alized 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) and
linked heterocyclic compounds [15]. One of the noteworthy
approaches for synthesis of this valuable type of compound
is the one-pot condensation of an aldehyde, β-ketoester
and urea under acidic conditions, first studied by Bigi-
nelli. Nonetheless, this reaction suffered from strict condi-
tion, frequent low yield and long reaction time [16]. Lately,
3,4-dihydropyrimidin-2(1H)-one (DHPM) framework has
been under lots of research [17–19] as it has a wide phar-
macological qualities, for instance anti-inflammatory [20],
antihypertensive agents [21], antitumor agents [22], antiviral
[23], antifungal [24] and calcium channel modulators [25].
Another one of the most noteworthy and conventional
MCRs is the synthesis of dihydropyridine (DHP) and its
derivatives which is attributed to Arthur Hantzsch who dis-
covered them in 1881 [26]. Recently, great attention has
been paid to the synthesis of Hantzsch polyhydroquinoline
derivatives owing to its biological and physiological prop-
erties [27]. Although dihydropyridines were mainly devel-
oped as cardiovascular agents, they are antihypertensive,
antiatherosclerotic, bronchodilator, vasodilator, geroprotec-
tive, antitumor, antimutagenic, hepatoprotective and anti-
diabetic agents [28]. Their broad pharmacological proper-
ties have interested the researchers to find novel derivatives
which are more selective, effective and maybe with several
modes of action [29].
Conversely, reduction in the amount of required sulfuric
acid and/or overview in handling processes is needed for
risk reduction, environment conservation and economic
improvement [12]. Furthermore, heterogeneous systems
attract attention and are studied owing to the significance
they have in industry and developing knowledge [13]. In
continuation of our researches on the application of solid
acids [6–11] and inorganic acidic salts [14], we found that
Scheme 1 Synthesis of nanometasilica sulfuric acids as two elegant silica-based catalysts with sulfuric acid moieties
1 3

J IRAN CHEM SOC
On the other hand, 2,3-dihydro-2-aryl-4(1H)-quina-
zolinone derivatives are a type of fused heterocycles
which have drawn much attention due to their poten-
tially biological and pharmaceutical activities as diu-
retic, antitumor and herbicidal agents, in addition to plant
growth regulators [30–34]. Three-component reaction of
aldehyde, isatoic anhydride and amine [35–39], reduc-
tion cyclization of orthoformate and o-nitrobenzamides,
aldehydes or ketones [40] and reduction of quinazolin-
4(3H)-ones [41] are also studied for the synthesis of
2,3-dihydroquinazolin-4(1H)-ones.
Consequently, the described novel catalysts were used
for the well-known Biginelli-type reaction in the synthe-
sis of 3,4-dihydropyrimidin-2(1H)-ones [42–63], Hantzsch
polyhydroquinolines synthesis [64–70] and 2,3-dihydro-
quinazolin-4(1H)-ones [71–75] via one-pot condensation
reaction under solvent-free benign conditions (Scheme 2).
400 MHz and 13C NMR 100) in pure deuterated DMSO with
tetramethylsilane (TMS) was used as the internal standard.
The synthesized catalysts were identified using IR, X-ray
diffraction patterns (XRD), scanning electron microscopy
(SEM), transmission electron microscopy (TEM), energy-
dispersive X-ray spectroscopy (EDX), thermal gravimetric
(TG) and derivative thermal gravimetric (DTG) analysis.
X-ray diffraction (XRD) patterns of two catalysts were
achieved on a APD 2000, Ital structure with Cu K_ radia-
tion (k = 0.1542 nm) operating at 50 kV and 20 mA in a 2-h
range of 10°–70° with step size 0.01° and time step 1.0 s
to assess the crystallinity of the catalysts. Fourier transform
infrared spectra of the samples were recorded on a Perki-
nElmer FT-IR spectrometer 17,259 by KBr disks. Thermal
gravimetric analyses using a PerkinElmer TGA were carried
out on catalysts. The SEM analyses were prepared with a
TESCAN/MIRA with a maximum acceleration voltage of
the primary electrons between 10 and 15 kV. Transmission
electron microscope, TEM measurements were carried out
on a Philips CM10 analyzer (operating at 120 kV). Semi-
quantitative EDX (Röntec, Quantax/QX2) analysis was
used for the characterization of element concentration.
Experimental
The materials were obtained from Merck, Fluka and Sigma-
Aldrich and were applied without any additional purifica-
tion. All reactions were observed via thin layer chromatog-
raphy (TLC) on gel F254 plates. Spectrometer (1H NMR
General procedure for the synthesis of nanometasilica
disulfuric acid (NMSDSA) as a green catalyst
To a round-bottomed flask (50 mL) including sodium meta-
silicate (5 mmol; 0.610 g) chlorosulfonic acid (10 mmol;
1.165 g; 0.665 mL) was added dropwise which in situ was
reacted (with a ratio of 1:2) and was stirred over a period of
30 min at room temperature. Then, the yellow solid prod-
uct was washed three times with diethyl ether and then dried
under vacuum conditions (Scheme 1). Nanometasilica disul-
furic acid (NMSDSA) with melting point of >380 °C (was
decomposed) was fully characterized by FT-IR, energy-
dispersive X-ray spectroscopy (EDX), X-ray diffraction
patterns (XRD), scanning electron microscopy (SEM) and
transmission electron microscopy (TEM) analysis.
O
O
O
S
Si
O
O Na
Cat
(10 mol%)
80 o
H
O
C
Nanometasilica mono sulfuric acid
Solvent-free,
sodium salt
(NMSMSA)
O
O
O
O
O
or
S
Si
S
O
O
H
H
O
O
R
Nanometasilica disulfuric acid
(NMSDSA)
X
=
or
S
X
O
O
H2N
NH2
3
HN
O
CHO
R
O
+
4
X
N
H
O
O
2
1
R
O
O
General procedure for the synthesis of nanometasilica
monosulfuric acid sodium salt (NMSMSA) as a green
catalyst
CHO
O
O
R'
R'
+
+
OR''
O
R'
R'
R''O
O
R
5
2
1
7
N
H
NH4OAc
To a round-bottomed flask (50 mL) counting sodium metasil-
icate (5 mmol; 0.610 g) chlorosulfonic acid (5 mmol; 0.583 g;
0.333 mL) was added dropwise which in situ was reacted
(with a ratio of 1:1) and was stirred over a period of 30 min at
room temperature. Then, the white solid product was washed
three times with diethyl ether and then dried under vacuum
conditions (Scheme 1). Nanometasilica monosulfuric acid
sodium salt (NMSMSA) with melting point of >394 °C (was
decomposed) was fully characterized by FT-IR, energy-dis-
persive X-ray spectroscopy (EDX), X-ray diffraction patterns
6
O
O
CHO
NH
NH2
R
+
N
H
NH2
R
8
9
1
Scheme 2 Synthesis of 3,4-dihydropyrimidin-2(1H)-one, polyhyd-
roquinoline and 2,3-dihydroquinazolin-4(1H)-one derivatives using
NMSDSA and NMSMSA as two elegant nanocatalysts with silica
sulfuric acid moieties
1 3

J IRAN CHEM SOC
(XRD), scanning electron microscopy (SEM) and transmis-
sion electron microscopy (TEM) analysis.
was added to a mixture of aromatic aldehydes (1 mmol)
and 2-aminobenzamide (1 mmol; 0.136 g) in a round-
bottomed flask, and the subsequent mixture was initially
stirred magnetically under solvent-free conditions at
80 °C. After completion of the reaction, as known by TLC
n-hexane/ethyl acetate (5:2), ethyl acetate (10 mL) was
added to a reaction mixture, stirred and refluxed for 5 min,
and then was washed with water (10 mL) and decanted to
separate catalyst from the reaction mixture (the reaction
mixture was soluble in hot ethyl acetate and NMSDSA or
NMSMSA catalyst was soluble in water). The solvent of
organic layer was evaporated, and the crude product was
purified via recrystallization from ethanol/water (10:1).
General procedure for the synthesis
of 3,4‑dihydropyrimidin‑2(1H)‑one derivatives
via Biginelli‑type reaction
Nanometasilica disulfuric acid (NMSDSA) (10 mol %;
0.024 g) or nanometasilica monosulfuric acid sodium salt
(NMSMSA) (10 mol %; 0.018 g) as a green mild catalyst
was added to a mixture of aromatic aldehydes (1 mmol), ethyl
acetoacetate (1 mmol; 0.132 g) and urea (1.5 mmol; 0.090)
or thiourea (1.5 mmol; 0.114) in a round-bottomed flask, and
the subsequent mixture was firstly stirred magnetically under
solvent-free conditions at 80 °C. After completion of the reac-
tion, as checked by TLC n-hexane/ethyl acetate (5:2), ethyl
acetate (10 mL) was added to a reaction mixture, stirred and
refluxed for 5 min, and then was washed with water (10 mL)
and decanted to separate catalyst from the reaction mixture
(the reaction mixture was soluble in hot ethyl acetate and
NMSDSA or NMSMSA catalyst was soluble in water). The
solvent of organic layer was evaporated, and the crude product
was purified via recrystallization from ethanol/water (10:1).
Ethyl 4‑(3‑ethoxy‑4‑hydroxyphenyl)‑6‑me‑
thyl‑2‑oxo‑1,2,3,4‑tetrahydropyrimidine‑5‑carboxylate
(Table 5, entry 10)
White solid; M.p: 192–194 °C; IR (KBr): υ 3427, 3188,
2991, 1667, 1585, 1476, 1333, 1284, 1194 cm−1; 1H NMR
(400 MHz, DMSO-d6): δppm 1.12 (t, 6H, J = 7.2 Hz, —
CH3), 2.25 (s, 3H, —CH3), 3.99 (q, 4H, J = 7.2 Hz,
—CH2), 5.11 (s, 1H, —CH aliphatic), 7.11 (d, 2H,
J = 7.6 Hz, ArH), 7.13 (s, 1H, ArH), 7.63 (s, 2H, —NH),
9.10 (s, 1H, —OH); 13C NMR (100 MHz, DMSO-d6): δppm
14.5, 18.1, 21.0, 54.1, 59.5, 60.3, 99.9, 100.1, 126.5, 129.3,
1368, 142.4, 148.5, 152.6, 165.8, 169.3.
General procedure for the synthesis
of polyhydroquinoline derivatives via Hantzsch
condensation reaction
Nanometasilica disulfuric acid (NMSDSA) (10 mol %;
0.024 g) or nanometasilica monosulfuric acid sodium salt
(NMSMSA) (10 mol %; 0.018 g) as a green mild catalyst was
added to a mixture of aromatic aldehydes (1 mmol), ethyl ace-
toacetate (1 mmol; 0.132 g) or methyl acetoacetate (1 mmol;
0.116 g), dimedone (1 mmol; 0.140 g) or 1,3-cyclohexan-
edione (1 mmol; 0.112 g) and ammonium acetate (1 mmol;
0.077 g) in a round-bottomed flask, and the consequent mix-
ture was first stirred magnetically under solvent-free condi-
tions at 80 °C. After completion of the reaction, as identified
by TLC n-hexane/ethyl acetate (5:2), ethyl acetate (10 mL)
was added to a reaction mixture, stirred and refluxed for 5 min,
and then was washed with water (10 mL) and decanted to sep-
arate catalyst from the reaction mixture (the reaction mixture
was soluble in hot ethyl acetate and NMSDSA or NMSMSA
catalyst was soluble in water). The solvent of organic layer
was evaporated, and the crude product was purified via recrys-
tallization from ethanol/water (10:1).
Ethyl 4‑(3‑ethoxy‑4‑hydroxyphenyl)‑6‑methyl‑2‑thi‑
oxo‑1,2,3,4‑tetrahydropyrimidine‑5‑carboxylate (Table 5,
entry 20)
White solid; M.p: 213–215 °C; IR (KBr): υ 3416, 3264,
3127, 2983, 1702, 1654, 1602, 1474, 1277, 1098 cm−1; 1H
NMR (400 MHz, DMSO-d6): δppm 1.12 (t, 3H, J = 7.6 Hz,
—CH3), 1.33 (t, 3H, J = 7.6 Hz, —CH3), 2.23 (s, 3H, —
CH3), 4.02 (q, 4H, J = 7.6 Hz, —CH2), 5.04 (s, 1H, —
CH aliphatic), 6.72 (d, 2H, J = 8.0 Hz, ArH), 6.78 (s, 1H,
ArH), 7.56 (s, 1H, —NH), 8.75 (s, 1H, —NH), 9.05 (s, 1H,
—OH); 13C NMR (100 MHz, DMSO-d6): δppm 14.5, 15.2,
18.1, 54.0, 59.5, 64.4, 100.1, 112.9, 115.8, 118.9, 136.3,
146.6, 146.7, 148.2, 152.6, 165.9.
Results and discussion
In continuation of our previous investigations linked to
the design, synthesis, applications and knowledge-based
improvement in novel solid acids [6–11] for organic func-
tional group transformations, herein, we wish to study syn-
thesis, characterization and applications of NMSMSA and
NMSDSA as two elegant and full-fledged catalysts with
silica sulfuric acid moieties.
General procedure for the synthesis
of 2,3‑dihydroquinazolin‑4(1H)‑one
Nanometasilica disulfuric acid (NMSDSA) (10 mol %;
0.024 g) or nanometasilica monosulfuric acid sodium salt
(NMSMSA) (10 mol %; 0.018 g) as a green mild catalyst
1 3

J IRAN CHEM SOC
Characterization of novel silica‑based catalyst
with silica sulfuric acid moieties: nanometasilica
disulfuric acid (NMSDSA) as a catalyst
The structure of nanometasilica disulfuric acid (NMS-
DSA) as a green mild and full-fledged catalyst with sil-
ica sulfuric acid moiety was considered and fully char-
acterized by FT-IR, EDX, XRD, SEM, TEM and TG
analysis.
The FT-IR spectrum of the nanostructured NMSDSA
displayed two abroad peaks at 3480 and 3417 cm−1 which
can be related to O–H stretching on –SO3H group. Moreo-
ver, two peaks at 1283 and 1176 cm−1 are linked to vibra-
tional modes of O–SO2 bonds. The absorption peak con-
nected to S=O bond vibration appeared at 1055 cm−1. Also,
two absorption peaks of the SiO3 at 1098 and 518 cm−1 are
related to the stretching vibration of Si–O groups (Fig. 1).
The energy-dispersive X-ray spectroscopy (EDX) of nano-
structured NMSDSA has revealed the presence of oxygen
(O), silicon (Si) and sulfur (S) composition in the pure cata-
lyst (Fig. 2). It is clearly shown that the synthesized NMSDSA
catalyst involves only O, Si and S and elements, which is pre-
sented in Fig. 2. No extra peak linked with any impurity has
been known in the SEM coupled EDX, which approves that
the NMSDSA catalyst is composed of just with O (78.59), Si
(4.21) and S (17.21) which is exposed in elemental analysis.
The structure of NMSDSA was studied via X-ray diffrac-
tion (XRD) pattern (Fig. 3). Peak width (FWHM), size and
inter-planer distance linked to XRD pattern of NMSDSA
were studied in the 19.00°–29.60°, and the achieved results
are summarized in Table 1. For instance, assignments for
the highest diffraction line 29.40° offered that an FWHM of
Fig. 2 EDX spectrum of the nanometasilica disulfuric acid (NMS-
DSA) as a novel green mild catalyst
0.58, a crystalline size of the catalyst of ca. 14.16 nm via the
Scherrer equation [D = Kλ/(βcosθ)] (where D is the mean
size of the arranged (crystalline) domains, which may be
smaller or equal to the grain size. K is a dimensionless shape
factor. The shape factor has a model value of about 0.9. λ is
the X-ray wavelength. β is the line width at half the maxi-
mum intensity (FWHM), after subtracting the instrumental
line width, in radians. θ is the Bragg diffraction angle in
degree, and an inter-planer distance of 0.303439 nm (the
similar highest diffraction line at 29.40°) was investigated
via the Bragg equation: [dhkl = λ/(2sinθ)], [(λ:Cu radiation
(0.154,178 nm)] were achieved. Achieving crystalline sizes
Fig. 1 IR spectrum of the nanometasilica disulfuric acid (NMSDSA) as a novel green mild catalyst
1 3

J IRAN CHEM SOC
thermal decomposition of the catalyst. The thermal gravi-
metric analysis of the NMSDSA catalyst offered remark-
able loss in two steps and decomposed after 400 °C.
Characterization of novel catalyst with silica sulfuric
acid moiety: nanometasilica monosulfuric acid sodium
salt (NMSMSA) as a catalyst
The structure of nanometasilica monosulfuric acid sodium
salt (NMSMSA) as an elegant and benign catalyst with
silica sulfuric acid moiety was studied and fully identified
by FT-IR, EDX, XRD, SEM, TEM and TG analysis.
The FT-IR spectrum of the nanostructured NMSMSA
shows an abroad peak at 3439 cm−1 which can be con-
nected to O–H stretching on –SO3H group. Furthermore,
two peaks at 1035 and 967 cm−1 are related to vibrational
modes of O–SO2 bonds. The absorption peak linked to
S=O bond vibration appeared at 897 cm−1. Additionally,
two absorption peaks of the SiO3 at 897 and 526 cm−1 are
correlated with the stretching vibration of Si–O groups
(the peaks of Si–O group overlaps with the peaks of S=O
bond and is shielded due to the ionic structure of catalyst)
(Fig. 6).
Fig. 3 X-ray diffraction (XRD) pattern of the nanometasilica disulfu-
ric acid (NMSDSA) as a novel green mild catalyst
Table 1 X-ray diffraction (XRD) data for the nanometa silica disul-
furic acid (NMSDSA) as a novel green mild catalyst
Entry
2θ
Peak width
Size (nm)
Inter-planer
[FWHM] (°)
distance (nm)
1
2
3
4
5
6
7
19.00
26.00
26.10
29.40
29.60
31.00
32.20
0.25
0.69
0.84
0.58
0.120
0.22
0.21
32.20
11.82
9.71
0.466531
0.342297
0.341008
0.303439
0.301434
0.288133
0.277663
Energy-dispersive X-ray spectroscopy (EDX) from the
attained nanostructured NMSMSA provided the presence
of the probable elements in the structure of the catalyst, for
instance Na, O, Si, S and Cl (Fig. 7).
14.16
68.49
37.48
39.38
Nanometasilica monosulfuric acid sodium salt (NMS-
MSA) as a nanostructured catalyst was investigated by
X-ray diffraction (XRD) pattern (Fig. 8), scanning elec-
tron microscopy (SEM) and transmission electron micros-
copy (TEM) (Fig. 9). In this investigation, to confirm the
structure of NMSMSA, firstly its XRD pattern was stud-
ied. As exposed in Fig. 8, the XRD patterns of nanostruc-
tured organocatalyst show peaks at 2θ ≈ 18.30°, 19.50°,
25.30°, 25.60°, 27.30°, 27.50°, 28.60°, 28.90°, 30.30°,
31.50°, 39.00°, 48.30° and 52.20°, respectively; this was
approved by the described value of scanning electron
microscopy (SEM) and transmission electron microscopy
(TEM) (Fig. 9). Peak width (FWHM), size and inter-planar
distance related to XRD pattern of nanostructured catalyst
were investigated in the 18.30°–52.20° and the attained
results are summarized in Table 2. The average crystallite
size D was calculated via the Scherrer formula: D = Kλ/
(βcosθ); K is the Scherrer constant, λ being the X-ray
wavelength, β is the half-maximum peak width, and θ is
the Bragg diffraction angle. Consequently, the average size
of the nanostructured catalyst achieved from this equation
was found to be about 10.31–67.26 nm, which is mainly
in good accordance with the scanning electron microscopy
and transmission electron microscopy (Fig. 9).
from several diffraction lines through the Scherrer equation
were found to be in the nanometer range (9.71–68.49 nm),
which is specially in close agreement with the scanning
electron microscopy (SEM) and transmission electron
microscopy (TEM) (Fig. 4). To determine the morphology
and the size of the nanostructured NMSDSA catalyst, SEM
and TEM were considered. This image of the nanostruc-
tured NMSDSA catalyst shows that the size of these parti-
cles is about 70 nm (Fig. 4).
The thermal gravimetric (TG) and derivative thermal
gravimetric (DTG) analysis of nanometasilica disulfuric
acid (NMSDSA) as an efficient catalyst displays the mass
loss of organic materials as they decompose upon heating
(Fig. 5). The main weight loss from the NMSDSA cata-
lyst (room temperature to 110 °C) is due to the removal
of physically adsorbed water and organic solvents, which
were used in making the catalyst. The weight loss is about
2 %. The weight loss (13 %) between 110 and 185 °C is
qualified mainly to the thermal decomposition sulfuric acid
moiety of catalyst. NMSDSA catalyst demonstrates two-
step weight loss behavior. Weight loss of catalyst seems
about 13 % at 185–400 °C, which is contributed to the
The thermal gravimetric (TG) and derivative ther-
mal gravimetric (DTG) analysis exposed that NMSMSA
1 3

J IRAN CHEM SOC
Fig. 4 Scanning electron microscopy (SEM) (a, b) and transmission electron microscopy (TEM) (c, d) of the nanometasilica disulfuric acid
(NMSDSA) as a novel green mild catalyst
Also the weight loss (14 %) happened in the range of
198–415 °C, is qualified to the loss of chief NMSMSA
catalyst. The thermal gravimetric analysis of the catalyst
presented noteworthy loss in two steps, and decomposed
above 415 °C.
Application of nanometasilica disulfuric acid
(NMSDSA) and nanometasilica monosulfuric acid
sodium salt (NMSMSA) as two elegant and full‑fledged
catalysts with silica sulfuric acid moieties
Initially, to optimize the reaction conditions, the condensa-
Fig. 5 Thermal gravimetric (TG) and derivative thermal gravimetric
tion reaction of 4-methylbenzaldehyde, ethyl acetoacetate
and urea was selected as a typical reaction and different
amounts of NMSDSA and NMSMSA as two nanostruc-
tured catalysts at the range of 25–100 °C were studied
under solvent-free conditions (Table 3). As revealed in
Table 1, the worthy results were achieved when the reaction
was attained in the presence of 10 mol % of nanostructured
catalysts at 80 °C (Table 3, entry 12). No improvement
(DTG) analysis of the nanometasilica disulfuric acid (NMSDSA) as a
novel green mild catalyst
catalyst was very stable and there was no evident mass
loss below 390 °C (see Fig. 10). The significant weight
loss (4 %) between 115 and 198 °C is qualified chiefly
to the thermal decomposition of sulfuric acid moiety.
1 3

J IRAN CHEM SOC
Fig. 6 IR spectrum of the nanometasilica monosulfuric acid sodium salt (NMSMSA) as a novel benign catalyst
Fig. 8 X-ray diffraction (XRD) pattern of the nanometasilica mono-
sulfuric acid sodium salt (NMSMSA) as a novel green mild catalyst
for instance H2O, C2H5OH, CH3CN, CH3CO2Et and
CH2Cl2 were studied at 80 °C. The results are summarized
in Table 4. The results show that solvent-free condition was
the best choice in this reaction (Table 4, entry 1).
Fig. 7 EDX spectrum of the nanometasilica monosulfuric acid
sodium salt (NMSMSA) as a novel green and benign catalyst
After detecting the optimized reaction conditions,
the study was followed through performing the reaction
between several aldehydes, ethyl acetoacetate and urea or
thiourea. To display the general applicability of this process,
various aldehydes were capably reacted with ethyl acetoac-
etate and urea or thiourea in the related conditions. These
results stimulated us to consider the scope, limitations and
the overview of this synthetic procedure for numerous alde-
hydes under optimized conditions. As exposed in Table 5, a
series of aromatic aldehydes underwent electrophilic substi-
tution reaction with ethyl acetoacetate and urea or thiourea
to afford a different range of substituted 3,4-dihydropyrimi-
din-2(1H)-ones via Biginelli-type reaction with worthy to
excellent yields. The nature and electronic properties of the
was identified in the yield of reaction by increasing the
amount of the catalysts and temperature (Table 3, entries
13 and 14). Table 1 obviously shows that in the absence of
catalysts, the product was produced in a low yield (Table 3,
entries 1 and 2). A slight increase of the urea was known to
be desirable, and therefore, the molar ratio of ethyl acetoac-
etate and 4-methylbenzaldehyde to urea was investigated
at 1:1:1.5 (the yield of the reaction 84 % using 1 mmol of
urea was increased to 90 % using 2 mmol of urea).
To compare the effect of the solution in comparison with
solvent-free conditions, a mixture of 4-methylbenzalde-
hyde, ethyl acetoacetate and urea as typical reaction, using
10 mol % of nanostructured catalysts in numerous solvents,
1 3

J IRAN CHEM SOC
Fig. 9 Scanning electron microscopy (SEM) (a, b) and transmission electron microscopy (TEM) (c, d) of the nanometasilica monosulfuric acid
sodium salt (NMSMSA) as a novel green mild catalyst
Table 2 X-ray diffraction (XRD) data for the nanometasilica mono-
sulfuric acid sodium salt (NMSMSA) as a novel green mild catalyst
substituents on the aromatic ring affect the alteration rate,
and aromatic aldehydes having electron-withdrawing groups
on the aromatic ring react similarly as electron-donating
groups do (in terms of reaction time and isolated yields). As
it is shown in Table 5, the attained results (lower reaction
time and higher isolated yields) in the presence of urea were
more successful than the results of thiourea in this reaction
conditions. Correspondingly, the attained results displayed
that the NMSDSA as a nanostructured catalyst was better
than the results of NMSMSA as a nanostructured catalyst
(owing to production of desired products with higher yields
and shorter reaction time).
Furthermore, reusability of the NMSDSA and NMS-
MSA as two worthy nanostructured catalysts was approved
in the condensation of 4-methylbenzaldehyde, ethyl ace-
toacetate and urea. At the end of the reaction, ethyl acetate
was added to the reaction mixture and heated to extract
product and remained starting materials (the product and
Entry
2θ
Peak width
Size (nm)
Inter-planer
[FWHM] (°)
distance (nm)
1
18.30
19.50
25.30
25.60
27.30
27.50
28.60
28.90
30.30
31.50
39.00
48.30
52.20
0.37
0.33
0.79
0.139
0.49
0.42
0.48
0.122
0.47
0.37
0.14
0.35
0.14
21.75
24.43
10.31
58.61
16.69
19.47
17.08
67.26
17.51
22.31
60.21
24.88
63.20
0.484219
0.386257
0.351606
0.347553
0.326285
0.323957
0.311741
0.308574
0.294627
0.283672
0.230672
0.188206
0.175024
2
3
4
5
6
7
8
9
10
11
12
13
1 3

J IRAN CHEM SOC
Table 4 Result of solvent effect on the condensation reaction of
4-methylbenzaldehyde, ethyl acetoacetate and urea under solvent-free
conditions
Entry Solvent
Reaction time (min)
Yielda (%)
NMSDSA NMSMSA NMSDSA NMSMSA
1
Solvent-
free
25
30
95
90
2
3
4
5
6
H2O
120
30
120
30
45
30
45
50
85
75
86
75
45
78
82
84
90
C2H5OH
CH3CN
45
CH3CO2Et 30
CH2Cl2 45
Fig. 10 Thermal gravimetric (TG) and derivative thermal gravimetric
(DTG) analysis of the nanometasilica monosulfuric acid sodium salt
(NMSMSA) as a novel green mild catalyst
Reaction conditions: 4-metylbenzaldehyde (1 mmol), ethyl acetoac-
etate (1 mmol), urea (1.5 mmol)
a
Isolated yield
remained starting materials are soluble in hot ethyl acetate
but catalysts is insoluble in ethyl acetate). It is known that
the catalytic activities of the catalysts were restored within
the limits of the experimental errors for eight continuous
runs (Table 6). The recycled catalyst was also character-
ized by FT-IR spectrum after its application in the reac-
tion. The deactivations of the catalysts are low. The reac-
tion was scaled up to 10 mmol of 4-methylbenzaldehyde
and ethyl acetoacetate and 15 mmol of urea in the presence
of 100 mol % of catalysts at 80 °C. The results are summa-
rized in Table 6.
were studied under the same reaction conditions. After
optimization of the reaction conditions, to study the effi-
cacy and the scope of the offered process, various poly-
hydroquinoline derivatives (via one-pot four component
condensation between 1,3-diketone, β-ketoester, aromatic
aldehydes and ammonium acetate) and 2,3-dihydroquina-
zolin-4(1H)-one derivatives (via condensation between
aromatic aldehydes and 2-aminobenzamide) were syn-
thesized using 10 mol % of NMSDSA and NMSMSA as
catalyst under solvent-free reaction conditions. The results
are shown in Tables 7 and 8. The effects of substituents on
the aromatic rings were estimated strong in terms of yields
under these reaction conditions. Both classes of aromatic
To investigate more about the scope and limitations of
catalytic activities of the described nanostructured catalysts
in the other work, the Hantzsch synthesis of polyhydroqui-
noline and 2,3-dihydroquinazolin-4(1H)-one derivatives
Table 3 Result of amount of
Entry Catalyst amount
(mol %)
Reaction temperature
(°C)
Reaction time (min)
Yielda (%)
the catalyst and temperature on
the condensation reaction of
4-methylbenzaldehyde, ethyl
acetoacetate and urea under
solvent-free conditions
NMSDSA NMSMSA NMSDSA NMSMSA
1
–
r.t.
80
80
80
80
80
80
r.t.
50
60
70
80
100
80
120
120
120
120
120
60
120
120
120
120
120
60
20
50
83
87
89
90
93
71
80
85
89
95
95
95
15
45
78
82
84
85
88
66
75
80
84
90
90
90
2
–
3
2.5
3.5
5
4
5
6
7.5
9
7
60
60
8
10
10
10
10
10
10
25
120
120
120
60
120
120
120
60
9
10
11
12
13
14
25
30
25
30
25
30
Reaction conditions: 4-metylbenzaldehyde (1 mmol), ethyl acetoacetate (1 mmol), urea (1.5 mmol)
a
Isolated yield
1 3

J IRAN CHEM SOC
Table 5 Synthesis of substituted 3,4-dihydropyrimidin-2(1H)-ones via Biginelli-type reaction using NMSDSA and NMSMSA as two worthy
nanostructured catalysts
Yielda (%)
NMSDSA
Entry
Aldehyde
Urea or Thiourea
M.p (°C)
[References]
Time (min)
NMSDSA
NMSMSA
NMSMSA
1
4-Methylbenzaldehyde
Urea
25
35
20
15
23
10
20
30
25
20
10
20
30
20
25
15
15
25
25
25
30
40
25
20
28
15
25
35
30
25
15
25
35
25
30
20
20
30
30
30
95
87
86
85
89
89
94
83
86
90
85
92
85
87
90
86
85
93
89
91
90
82
81
80
84
84
89
88
81
85
80
87
80
82
85
81
80
88
84
86
203–205 [47]
227–229 [48]
181–183 [47]
231–233 [49]
220–222 [47]
226–228 [56]
213–215 [50]
205–207 [57]
208–210 [48]
192–194 [58]
>350 [59]
2
3-Nitrobenzaldehyde
Urea
3
4-Hydroxybenzaldehyde
2-Hydroxybenzaldehyde
2-Chlorobenzaldehyde
Urea
4
Urea
5
Urea
6
3,4-Dihydroxybenzaldehyde
4-Chlorobenzaldehyde
Urea
7
Urea
8
2-Hydroxy-3-methoxybenzaldehyde
4-Nitrobenzaldehyde
Urea
9
Urea
10
11
12
13
14
15
16
17
18
19
20
3-Ethoxy-4-hydroxybenzaldehyde
2,4-Dihydroxybenzaldehyde
4-Methylbenzaldehyde
Urea
Urea
Thiourea
Thiourea
Thiourea
Thiourea
Thiourea
Thiourea
Thiourea
Thiourea
Thiourea
214–216 [47]
211–213 [50]
166–168 [60]
172–174 [51]
209–211 [47]
237–239 [61]
208–210 [52]
207–209 [62]
213–215 [63]
3-Nitrobenzaldehyde
4-Hydroxybenzaldehyde
2-Hydroxybenzaldehyde
2-Chlorobenzaldehyde
3,4-Dihydroxybenzaldehyde
4-Chlorobenzaldehyde
4-Nitrobenzaldehyde
3-Ethoxy-4-hydroxybenzaldehyde
Reaction conditions: aldehyde (1 mmol), ethyl acetoacetate (1 mmol), urea or thiourea (1.5 mmol), NMSDSA and NMSMSA as two nanostruc-
tured catalysts (10 mol %), solvent-free, 80 °C
a
Isolated yield
Table 6 Reusability
of the catalysts on the
Entry
Reaction time (min)
Product isolated yield (%)
Catalyst isolated yield (%)
condensation reaction of
4-methylbenzaldehyde, ethyl
acetoacetate and urea under
solvent-free conditions at 80 °C
NMSDSA
NMSMSA
NMSDSA
NMSMSA
NMSDSA
NMSMSA
1
2
3
4
5
6
7
8
25
25
25
30
35
40
40
45
30
30
30
35
35
40
45
50
95
94
93
90
89
87
83
80
90
89
88
86
84
81
78
74
Fresh
98
Fresh
98
97
97
96
96
94
94
90
90
88
87
85
83
aldehydes containing electron-releasing and electron-
withdrawing substituents in their aromatic rings gained
the appropriate products in high to excellent yields in short
reaction times. The reaction times of aromatic aldehydes
having electron-withdrawing groups and electron-donat-
ing groups had rather same results. Similarly, the achieved
1 3

J IRAN CHEM SOC
Table 7 Hantzsch synthesis of polyhydroquinolines using NMSDSA and NMSMSA as nanostructured catalysts
Yielda (%)
NMSDSA
Entry
Aldehyde
R′
R″
M.p (°C)
[References]
Time (min)
NMSDSA
NMSMSA
NMSMSA
1
2
3
4
5
4-Hydroxy-3-methoxybenzaldeyhe
Terephthaldehyde
H
Me
Et
20
20
15
20
20
25
25
20
25
25
94
91
94
93
93
92
90
91
90
90
223–225 [64]
343–345 [64]
228–230 [64]
233–235 [65]
242–244 [65]
Me
Me
Me
Me
4-N,N-Dimethylaminobenzaldehyde
4-Chlorobenzaldeyhe
Me
Et
4-Nitrobenzaldeyhe
Et
Reaction conditions: aldehyde (1 mmol), 1,3-diketone (1 mmol), β-ketoester (1 mmol), ammonium acetate (1 mmol), NMSDSA and NMSMSA
as two nanostructured catalysts (10 mol %), solvent-free, 80 °C
a
Isolated yield
Table 8 Synthesis of
O
O
CHO
R
2,3-dihydroquinazolin-
4(1H)-one derivatives using
NMSDSA and NMSMSA as
nanostructured catalysts
or
NMSMSA NMSDSA
NH
9
NH2
NH2
(10 mol%)
Solvent-free, 80 o
+
R
C
N
H
8
1
Yielda (%)
Entry Aldehyde
M.p (°C) [References]
Time (min)
NMSDSA NMSMSA NMSDSA NMSMSA
1
2
3
4
5
4-Methylbenzaldehyde 10
10
10
15
12
12
93
93
91
92
93
92
91
90
91
92
250–252 [71]
215–217 [71]
235–237 [71]
231–233 [71]
180–182 [71]
Benzaldehyde
10
15
4-Chlorobenzaldehyde
3-Hydroxybenzaldehyde 10
3-Nitrobenzaldehyde 12
Reaction conditions: aldehyde (1 mmol), 2-aminobenzamide (1 mmol), NMSDSA and NMSMSA as two
nanostructured catalysts (10 mol %), solvent-free, 80 °C
a
Isolated yield
results exhibited that the NMSDSA as a nanostructured
catalyst was better than the results of NMSMSA as a nano-
structured catalyst (because of synthesis of preferred prod-
ucts with higher yields and shorter reaction time).
application was studied in the synthesis of 3,4-dihydropy-
rimidin-2(1H)-one, polyhydroquinoline and 2,3-dihydro-
quinazolin-4(1H)-one derivatives under solvent-free benign
conditions. NMSDSA and NMSMSA were fully charac-
terized by FT-IR, energy-dispersive X-ray spectroscopy
(EDX), X-ray diffraction patterns (XRD), scanning elec-
tron microscopy (SEM), transmission electron microscopy
(TEM) and thermal gravimetric analysis (TGA). The sug-
gested mechanism exposed that the buffer ability of NMS-
DSA and NMSMSA probably plays a noteworthy and dual
catalytic role in the defined reaction. Finally, main advan-
tages of the offered methodology and/or investigation are
reasonably simple work-up, high yield, short reaction time,
Conclusion
In summary, two benign, efficient and full-fledged nano-
structured catalysts with silica sulfuric acid moieties,
namely nanometasilica disulfuric acid (NMSDSA) and
nanometasilica monosulfuric acid sodium salt (NMS-
MSA), were designed and synthesized, and their catalytic
1 3

J IRAN CHEM SOC
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Acknowledgments We thank Bu-Ali Sina University, Iran National
Science Foundation (INSF) (the Grant of Allameh Tabataba’i’s
Award, Grant Number BN093) and National Elites Foundation for
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