Nano-SiO2: A green, efficient, and reusable heterogeneous catalyst for the synthesis of quinazolinone derivatives

Article abstract of DOI:10.1007/s13738-014-0533-4

A highly efficient and general method is applied for the multicomponent synthesis of quinazolinone derivatives from cyclocondensation of aromatic aldehydes and dimedone with 2-amino benzimidazole or 3-amino-1,2,4-triazole using nano-SiO₂ as a c

Full text of DOI:10.1007/s13738-014-0533-4

J IRAN CHEM SOC
DOI 10.1007/s13738-014-0533-4
ORIGINAL PAPER
Nano‑SiO2: a green, efficient, and reusable heterogeneous catalyst
for the synthesis of quinazolinone derivatives
Mir Rasul Mousavi · Malek Taher Maghsoodlou
Received: 20 May 2014 / Accepted: 26 August 2014
© Iranian Chemical Society 2014
Abstract A highly efficient and general method is applied
for the multicomponent synthesis of quinazolinone deriva-
tives from cyclocondensation of aromatic aldehydes and
dimedone with 2-amino benzimidazole or 3-amino-1,2,4-
triazole using nano-SiO2 as a catalyst in acetonitrile at
room temperature. In this method, nano-SiO2 was used as
a green and reusable catalyst. This synthetic method pro-
vides several advantages including excellent yields, short
reaction times, simple workup, mild conditions and inex-
pensiveness, green, and recyclable.
organic reactions, MCRs are profitable in being highly con-
vergent and in requiring the minimum effort to be achieved.
One of the important compounds derived from MCRs is
nitrogen-containing compounds [6, 7] because nitrogen-
containing heterocycles are abundant in nature and exhibit
diverse and important biological properties [8–11]. Among
such heterocycles, quinazoline and quinazolinone deriva-
tives exhibited interesting pharmacological activities. Dis-
eases of the arterial tree cause more premature deaths than
all the other diseases such as cancer and infections com-
bined. Among the major risk factors for arterial diseases,
high blood pressure has been identified as the most power-
ful one [12]. Quinazolines and condensed quinazolines are
reported to possess interesting pharmacological activities
such as antihypertensive [13–15], analgesic and antiinflam-
matory [16, 17], antihistaminic [18, 19], anticancer [20],
and anti-HIV [21] activities. Also, the quinazolinone deriva-
tives exhibited more potent activity in anesthetized animals
[22]. Moreover, many naturally occurring and synthetic
compounds containing the benzimidazole and triazole deriv-
ative scaffolds possess interesting pharmacological prop-
erties [23, 24]. A potent antihypertensive activity has been
observed in 1,2,4-triazoloquinazoline derivatives [25]. There
are a few methods reported in the literature [26] for the syn-
thesis of triazolo/benzimidazoloquinazolinones derivatives
which include a three-component condensation of aromatic
aldehydes and dimedone with 2-aminobenzimidazole/3-
amino-1,2,4-triazole using H6P2W18O62•18H2O [27], micro-
wave [28], molecular iodine (I2) [29], and refluxing in DMF
[30, 31]. However, some of these procedures are lengthy and
require expensive and hazardous catalysts and result in poor
yields. Synthetic alternatives are many and varied, and have
resorted to harsh conditions, for example, requiring reflux-
ing conditions. Therefore, the development of simple, effi-
cient, inexpensive, nontoxic, and readily available reagents
Keywords Triazoloquinazolinone ·
Benzimidazoquinazolinone · Nano-SiO2 · Heterogeneous
catalyst · Reusable catalyst
Introduction
The advent of combinatorial chemistry has in the recent past
emerged as a powerful tool for the rapid generation, identifi-
cation and optimization of lead compounds in the drug dis-
covery processes [1–3]. Multi-component reactions (MCRs)
[4, 5], reactions in which more than two starting materials all
present simultaneously together in one reaction vessel com-
bine to form a final product and have accordingly been used
to efficiently generate chemical diversity in the final prod-
ucts in a few reaction steps. Compared with conventional
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-014-0533-4) contains supplementary
material, which is available to authorized users.
M. R. Mousavi · M. T. Maghsoodlou (*)
Department of Chemistry, Faculty of Science, University
of Sistan and Baluchestan, PO Box 98135-674, Zahedan, Iran
e-mail: mt_maghsoodlou@chem.usb.ac.ir
1 3

J IRAN CHEM SOC
R
N
General procedure for the preparation of triazoloquina-
zolinones 4 and benzimidazoquinazolinones 6
NH2
N
O
N
N
N
N
H
3
N
To a mixture of dimedone (1 mmol), aldehyde (1 mmol),
2-aminobenzimidazole or 3-amino-1,2,4-triazole (1 mmol)
and nano-SiO2 (15 mol %) in the acetonitrile (5 mL) was
stirred for appropriate time (Table 2) at 25–30 °C. After
the completion of the reaction as indicated by TLC, dichlo-
romethane (CH2Cl2) was added to the solidified mixture
and the insoluble catalyst was separated by filtration. Evap-
oration of the solvent from the filtrate and recrystalliza-
tion of the solid residue from hot ethanol afforded the pure
products in high yields.
H
O
CHO
+
4a-4j
Nano-SiO2/ 15 mol%
CH3CN, r.t
R
O
R
N
NH2
1
2
O
N
H
N
R: Me, OMe, NO2, F, Cl, Br,...
5
N
N
H
6a-6h
Scheme1 Synthesis of triazoloquinazolinone 4 and benzimidazo-
quinazolinone 6 derivatives using nano-SiO2
providing convenient procedures with improved yields is
necessary. Herein, we report a simple, rapid and one-pot
procedure for the synthesis of triazoloquinazolinones and
benzimidazoquinazolinones using nano catalyst. Nanotech-
nology is a growing and important field in the modern sci-
ences. Nano-sized catalysts continue to attract attention for
different research areas due to their different physical and
chemical properties when compared to bulk material. The
extremely small-sized particles maximized the surface area
which was exposed to the reactant, allowing more reactions
to occur at the same time, thus speeding up the process. To
the best of our knowledge, there is no report of the use of
nano materials as catalyst for the synthesis of triazoloquina-
zolinones and benzimidazoquinazolinones. In view of the
importance of heterogeneous solid nano materials as reus-
able catalysts in organic synthesis [32–35], herein we report
the use of nano-SiO2 as a recyclable green catalyst for the
synthesis of triazoloquinazolinones and benzimidazoquina-
zolinones (Scheme 1).
6,7-Dihydro-6,6-dimethyl-9-p-tolyl-[1,2,4]triazolo[5,1-b]
quinazolin-8(4H,5H,9H)-one (4d)
White solid (93 % yield), m.p. = 263–265 °C; IR (KBr,
cm−1) 3421, 3036, 2964, 1649, 1578, 1364, 1259, 757;
1H NMR (400 MHz, DMSO) δ = 0.96 (s, 3H, CH3), 1.04
(s, 3H, CH3), 2.07 (d, 1H, J = 16.0 Hz, H-5), 2.20 (d, 1H,
J = 12.0 Hz, H′-5), 2.28 (s, 3H, CH3), 2.48–2.59 (m, 2H,
H-7), 6.16 (S, 1H, H-9), 7.07 (s, 4H, Ar–H), 7.67 (s, 1H,
H-2), 11.09 (s, 1H, NH).
6,7-Dihydro-9-(2,4-dimethoxyphenyl)-6,6-dime-
thyl-[1,2,4]triazolo[5,1-b]quinazolin-8(4H,5H,9H)-one (4f)
White solid (88 % yield); m.p. 208–210 °C; IR (KBr, cm−1):
3150, 3093, 3030, 2959, 2933, 1694, 1652, 1579, 1508,
1
1416, 1338, 1294, 1183, 1038, 826; H NMR (400 MHz,
CDCl3): δ = 1.07 (s, 3H, CH3), 1.15 (s, 3H, CH3),
2.22 (d, J = 16.0 Hz, 1H, H-5), 2.29 (d, J = 16.0 Hz, 1H,
H′-5), 2.48 (d, J = 16.0 Hz, 1H, H-7), 2.59 (d, J = 16.0 Hz,
1H, H′-7), 3.71 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 6.40
(d, J = 2.4 Hz, 1H, Ar–H), 6.47 (dd, J = 8.0, 4.0 Hz, 1H,
Ar–H), 6.56 (s, 1H, H-9), 7.38 (d, J = 8.0 Hz, 1H, Ar–H),
7.64 (s, 1H, H-2), 11.76 (s, 1H, NH).
Experimental
General
The melting point and IR spectra of all compounds were
obtained on an Electrothermal 9100 apparatus and a
JASCO FT/IR-460 plus spectrometer, respectively. 1H
and 13C NMR spectra of compounds were recorded on a
Bruker DRX-400 Avance instrument in DMSO at 400 and
100 MHz, respectively. Elemental analyses for the new
compounds for C, H, and N were performed using a Her-
aeus CHN-O-Rapid analyzer. The mass spectra for the new
compounds were recorded on an Agilent Technology (HP)
mass spectrometer, operating at an ionization potential of
70 eV. All reagents were purchased from Merck (Darm-
stadt, Germany), Acros (Geel, Belgium) and Fluka (Buchs,
Switzerland). Also, nano-SiO2 was purchased from Canada
(MKN-SiO2-015P).
6,7-Dihydro-6,6-dimethyl-9-(naphthalen-2-yl)-[1,2,4]triaz
olo[5,1-b]quinazolin-8(4H,5H,9H)-one (4i)
White solid (97 % yield); m.p. 268–270 °C; IR (KBr,
cm−1): 3416, 3246, 3091, 2963, 2927, 1652, 1574, 1469,
1410, 1364, 1335, 1251, 779; 1H NMR (400 MHz,
DMSO): δ = 0.97 (s, 3H, CH3), 1.05 (s, 3H, CH3), 2.06 (d,
J = 16.0 Hz, 1H, H-5), 2.23 (d, J = 16.0 Hz, 1H, H′-5),
2.58 (dd, J = 16.0, 24.0 Hz, 2H, H-7), 6.38 (S, 1H, H-9),
7.26 (dd, J = 4.0, 8.0 Hz, 1H, Ar–H), 7.48–7.50 (m, 2H,
Ar–H), 7.69 (s, 1H, H-2), 7.80 (d, J = 4.0 Hz, 1H, Ar–H),
7.84 (d, J = 8.0 Hz, 2H, Ar–H), 7.90 (t, J = 4.0 Hz, 1H,
Ar–H), 11.20 (s, 1H, NH).
1 3

J IRAN CHEM SOC
9-(2-Bromophenyl)-6,7-dihydro-6,6-dimethyl-[1,2,4]triazo
lo[5,1-b]quinazolin-8(4H,5H,9H)-one (4j)
1.04 (s, 3H, CH3), 1.99 (d, 1H, J = 12.0 Hz, H-4), 2.24
(d, 1H, J = 16.0 Hz, H′-4), 2.55 (d, 1H, J = 8.0 Hz, H-2),
2.66 (d, 1H, J = 8.0 Hz, H′-2), 6.71 (S, 1H, H-12), 6.83 (t,
1H, J = 8.0 Hz, Ar–H), 6.8–6.99 (m, 3H, Ar–H), 7.26 (d,
1H, J = 8.0 Hz, Ar–H), 7.25 (d, 1H, J = 8.0 Hz, Ar–H),
7.30 (d, 1H, J = 8.0 Hz, Ar–H), 7.34 (d, 1H, J = 8.0 Hz,
Ar–H), 10.03 (s, 1H, NH), 11.11 (s, 1H, NH); 13C NMR
(100 MHz, DMSO) δ = 27.0, 29.3, 32.4, 48.3, 50.5, 105.8,
110.5, 112.2, 113.2, 114.7, 117.1, 118.3, 119.2, 120.5,
121.3, 121.9,124.8, 125.6, 132.5, 136.7, 142.5, 146.0,
150.2, 193.2; MS (EI, 70 eV): m/z (%) = 382 (7) [M]+,
325 (3), 298 (9), 266 (34), 236 (6), 208 (4), 180 (14), 152
(12), 117 (100), 89 (43), 69 (9), 51 (39); Anal. Calcd for
C24H22N4O: C, 75.37; H, 5.80; N, 14.65. Found: C, 75.55;
H, 5.95; N, 14.70 %.
White solid (98 % yield), m.p. = 278–280 °C; IR (KBr,
cm−1) 3143, 3090, 2960, 1644, 1581, 1369, 1257, 753;
1H NMR (400 MHz, DMSO) δ = 1.01 (s, 3H, CH3),
1.05 (s, 3H, CH3), 2.05 (d, 1H, J = 16.0 Hz, H-5), 2.20
(d, 1H, J = 16.0 Hz, H′-5), 2.50–2.51 (m, 1H, H-7), 2.55
(d, 1H, J = 16.0 Hz, H′-7), 6.57 (S, 1H, H-9), 7.16–7.18
(m, 1H, Ar–H), 7.29 (d, 1H, J = 8.0 Hz, Ar–H), 7.54 (d,
1H, J = 8.0 Hz, Ar–H), 7.66 (s, 1H, H-2), 8.28 (s, 1H,
Ar–H), 11.22 (s, 1H, NH); 13C NMR (100 MHz, DMSO)
δ = 21.2, 27.4, 28.9, 32.6, 40.0, 50.2, 58.5, 125.9, 128.2,
128.5, 130.1, 133.3, 140.1, 147.2, 150.5, 151.5,193.3; MS
(EI, 70 eV): m/z (%) = 373 (2) [M]+, 293 (100), 266 (2),
139 (1), 217 (10), 183 (4), 161 (8), 127 (3), 105 (7), 83 (3),
55 (3); Anal. Calcd for C17H17BrN4O: C, 54.70; H, 4.59; N,
15.01. Found: C, 54.85; H, 4.50; N, 15.09 %.
Results and discussion
3,3-Dimethyl-12-phenyl-1,2,3,4,5,12-hexahydrobenzo[4,5]
imidazo[2,1-b]quinazolin-1-one (6a)
According to literature reports, utilities of the heteroge-
neous nano materials as new environmentally friendly
catalysts for the synthesis of biologically active molecules
have increased. Therefore, we describe a simple and effi-
cient method for the synthesis of triazoloquinazolinones
and benzimidazoquinazolinones using the environmen-
tally benign and reusable nano-SiO2 as a catalyst herein.
We would like to report the preparation of triazoloquina-
zolinone and benzimidazoquinazolinone derivatives
using reactions involving arylaldehydes, dimedone, and
2-aminobenzimidazole/3-amino-1,2,4-triazole (Scheme 1).
We chose the reaction of 4-methyl benzaldehyde 1, dime-
done 2 and 3-amino-1,2,4-triazole 3 in the presence of
nano-SiO2 in the acetonitrile as a model system for the
optimization study. Initially, a series of comparative
experiments were performed to compare the effective-
ness of different amounts of nano-SiO2 in the formation
of 6,7-dihydro-6,6-dimethyl-9-p-tolyl-[1,2,4]triazolo[5,1-
b]quinazolin-8(4H,5H,9H)-one 4d. The results are shown
in Table 1 and the best result was obtained in 15 mol % of
nano-SiO2. This amount of catalyst indicates a good yield
of product, while increasing the catalyst loading did not
further improve the results. The catalyst showed a very
good catalytic activity. This might be due to its small par-
ticle size, which provides a large surface area for reactant
adsorption and accordingly, a high catalytic activity. As
shown in Table 1, no product was obtained in the absence
of the catalyst (Table 1, entry 1). Also, the reaction did not
lead to the desired product under solvent-free conditions
(Table 1, entry 8). That might have been due to the lack of
effective interaction between reactants and the catalyst in
the absence of the solvent.
White solid (95 % yield), m.p. = >300 °C; IR (KBr, cm−1)
1
3430, 3093, 2956, 1643, 1615, 1569, 1376, 1257, 750; H
NMR (400 MHz, DMSO) δ = 0.92 (s, 3H, CH3), 1.05 (s,
3H, CH3), 2.05 (d, 1H, J = 16.0 Hz, H-4), 2.26 (d, 1H,
J = 16.0 Hz, H′-4), 2.45 (d, 1H, J = 16.0 Hz, H-2), 2.58
(d, 1H, J = 16.0 Hz, H′-2), 6.41 (S, 1H, H-12), 6.95 (t, 1H,
J = 8.0 Hz, Ar–H), 7.04 (t, 1H, J = 8.0 Hz, Ar–H), 7.15
(t, 1H, J = 8.0 Hz, Ar–H), 7.24 (t, 1H, J = 8.0 Hz, Ar–H),
7.33 (d, 3H, J = 8.0 Hz, Ar–H), 7.37 (q, 3H, J = 8.0 Hz,
Ar–H), 10.18 (s, 1H, NH).
3,3-Dimethyl-12-[2,4]dichlorophenyl-1,2,3,4,5,12-hexahyd
robenzo[4,5]imidazo[2,1-b]quinazolin-1-one (6b)
White solid (96 % yield); m.p. >300 °C; IR (KBr, cm−1):
3238, 3061, 2963, 2931, 1650, 1615, 1595, 1573, 1563,
1
1459, 1374, 1270, 737; H NMR (400 MHz, DMSO):
δ = 0.95 (s, 3H, CH3), 1.06 (s, 3H, CH3), 2.04 (d,
J = 16.0 Hz, 1H, H-4), 2.24 (d, J = 16.0 Hz, 1H, H′-4),
2.29 (d, J = 12.0 Hz, 1H, H-2), 2.33 (d, J = 16.0 Hz, 1H,
H′-2), 6.65 (S, 1H, H-12), 6.96 (t, J = 8.0 Hz, 1H, Ar–H),
7.03 (s, 1H, Ar–H), 7.08-7.12 (m, 1H, Ar–H), 7.38 (s, 1H,
Ar–H), 7.40 (s, 1H, Ar–H), 7.48 (d, J = 8.0 Hz, 1H, Ar–H),
11.25 (s, 1H, NH).
3,3-Dimethyl-12-(3-indolyl)-1,2,3,4,5,12-hexahydrobenzo[
4,5]imidazo[2,1-b]quinazolin-1-one (6h)
Pale yellow solid (94 % yield), m.p. = >300 °C; IR (KBr,
cm−1) 3470, 3415, 2925, 1647, 1615, 1570, 1442, 1372,
Moreover, the synthesis of 4d was separately carried
out in different solvents such as tetrahydrofuran (THF),
1
740; H NMR (400 MHz, DMSO) δ = 0.84 (s, 3H, CH3),
1 3

J IRAN CHEM SOC
ethanol, dichloromethane, and acetonitrile under the stir-
ring and at room temperature. Among the screened sol-
vent systems, acetonitrile was the solvent of choice, since
the reaction proceeded smoothly and afforded the desired
adducts in high yields. Also, the performance of bulk SiO2
was studied on model system and the product was obtained
in low yields (20–25 %) and undesired products were pro-
duced. Therefore, bulk of SiO2 cannot be suitable catalyst
for this reaction.
In continuation of our research to demonstrate the utility
and generality of this method, we used a diverse of alde-
hydes to investigate these three-component reactions under
the optimized conditions. We observed that various alde-
hydes could be introduced with high efficiency and pro-
duced products in high yields. As shown in Table 2, various
aromatic aldehydes in the presence of electron-withdraw-
ing or electron-releasing substituents, both of which gave
the desired product in excellent yields (Table 2).
We then explored the scope of this procedure in the
three-component synthesis of benzimidazoquinazolinone
derivatives 6, via the condensation of aromatic aldehydes
1, dimedone 2 and 2-aminobenzimidazole 5 under the opti-
mized conditions in Table 1. In all cases, the reaction pro-
ceeded smoothly and the desired products were obtained in
good yields. The results are summarized in Table 2.
Table 1 Condensation reaction of 3-amino-1,2,4-triazole, 4-methyl
benzaldehyde and dimedone in the presence of different loadings of
the catalyst at ambient conditions
CH3
O
NH2
N
O
CHO
N
Nano-SiO2 (mol%)
Solvent, r.t
N
N
N
+
+
N
H3C
O
H
N
H
1
2
3
4d
Entry Solvent/temp Catalyst (mol %) Time (min) Yield (%)a
1
2
3
4
5
6
7
8
CH3CN/rt
CH3CN/rt
CH3CN/rt
CH3CN/rt
CH3CN/rt
CH3CN/rt
CH3CN/rt
–/rt
–
180
30
–
5
81
86
93
90
89
91
–
All known products were identified by the comparison
of the melting points and the analytical data (IR, NMR)
with those reported for authentic samples. The structure of
new compounds 4j and 6h was deduced on the basis of IR,
1H NMR spectroscopy, 13C NMR spectroscopy, mass spec-
trometry, and elemental analysis. For example, the mass
spectrum of 4j displayed the molecular ion peak (M+) at
m/z = 373, which is consistent with the proposed struc-
10
15
20
25
30
15
20
15
30
35
20
180
All the reactions were carried out using 1 mmol of 4-methylbenzal-
dehyde, 1 mmol of dimedone and 1 mmol of 3-amino-1,2,4-triazole
with varying amounts of catalyst in CH3CN (5 mL) at room tem-
perature. Bold shows the best conditions for the reaction during the
course of the screening of different loadings of the catalyst
1
ture. The H NMR spectrum of 4j exhibited two singlet
at δ = 1.01 and 1.05 ppm for the geminal methyl protons.
Three doublets and one multiplet were observed at δ = 2.05
(J = 16.0 Hz), 2.20 (J = 16.0 Hz), 2.55 (J = 16.0 Hz) and
a
Yield refers to the pure isolated products
Table 2 Synthesis of various
Entry
R
Amine Product Time (min) Yield (%)a Mp (°C)
Lit. mp (°C) [Ref.]
triazoloquinazolinones and
benzimidazoquinazolinones in
the presence of nano-SiO2
1
H
3
3
3
3
3
3
3
3
3
3
5
5
5
5
5
5
5
5
4a
4b
4c
4d
4e
4f
30
45
10
15
20
18
20
14
20
15
25
20
30
25
15
18
20
45
96
89
94
93
97
85
90
98
93
98
95
97
98
87
95
91
95
94
248–250 248–250 [31]
2
4-OH
4-Cl
305–306 307–309 [27]
302–304 304–306 [29]
263–265 264–269 [27]
320–322 323–325 [29]
208–210 210–212 [29]
256–258 258–260 [28]
265–267 266–269 [29]
268–270 287–290 [29]
278–280 This workb
3
4
4-Me
5
2,4-(Cl)2
2,4-(OMe)2
4-F
6
7
4 g
4 h
4i
8
3-NO2
2-Naphthyl-
2-Br
9
10
11
12
13
14
15
16
17
18
4j
H
6a
6b
6c
6d
6e
6f
>300
>300
>300
>300
>300
>300
>300
>300
>300 [27]
>300 [29]
>300 [30]
>300 [28]
>300 [30]
>300 [27]
>300 [27]
This workb
2,4-Cl2
4-NO2
4-F
Column written in bold
indicates the number of product
was obtained
4-OMe
4-Cl
a
Yields refer to the pure
isolated products
4-Br
6 g
6 h
b
The new compounds
3-Indole-
synthesized in this work
1 3

J IRAN CHEM SOC
Table 3 Reusability of the nano-SiO2 in the reaction of
3-amino-1,2,4-triazole, 4-methyl benzaldehyde and dimedone for the
synthesis of 4d
at δ = 6.57 ppm. The aromatic protons resonance was
observed as multiplets at δ = 7.16–8.28 ppm. The proton of
the NH group was appeared as a singlet at δ = 11.22 ppm.
It is noteworthy that, in our procedure, products were
obtained without byproducts in good to high yields with
short reaction times and the reaction was carried out at
ambient temperature. In organic reactions, when a hetero-
geneous catalyst is used, the recyclability of the catalyst
is very important. To investigate the recyclability of nano-
SiO2, the reuse and recovery of the nano-SiO2 are highly
desirable, and five batches of the experiments were carried
out for the preparation of product 4d. The results are shown
in Table 3. The catalyst was filtered off and washed with
an excess of dichloromethane and reused in a new reaction.
Based on the obtained results and according to the pre-
vious reports on the catalytic synthesis of triazoloquina-
zolinones 4 and benzimidazoquinazolinones 6, two plausi-
ble mechanisms can be proposed for the synthesis of these
compounds in the presence of nano-SiO2. Therefore, this
reaction may occur via Knoevenagel condensation for the
formation of α, β-unsaturated carbonyl compounds 11 upon
the loss of water molecule (route A). Then, via an inter-
molecular Mannich type reaction α,β-unsaturated carbonyl
compounds, undergoing nucleophilic attack by amine, gave
CH3
O
NH2
N
O
CHO
N
Nano-SiO2
Solvent, r.t
N
N
N
+
+
N
H3C
O
H
N
H
1
2
3
4d
Run
Solvent/temp
Time (min)
Yield (%)a
1
2
3
4
5
CH3CN/rt
CH3CN/rt
CH3CN/rt
CH3CN/rt
CH3CN/rt
15
15
18
24
30
93
92
90
89
87
All the reactions were carried out using 1 mmol of 4-methylbenzal-
dehyde, 1 mmol of dimedone and 1 mmol of 3-amino-1,2,4-triazole
with varying amounts of catalyst in CH3CN (5 mL) at room tempera-
ture
a
Yield refers to the pure isolated products
2.50–2.51 for the diastereotopic methylene protons of
H-5, H′-5, H′-7 and H-7, respectively. The methine pro-
ton of the central ring (H-9) was observed as a singlet
Scheme 2 Plausible mecha-
nisms (A and B) for the synthe-
sis of quinazolinone derivatives
4a–4j and 6a–6h
SiO2
SiO2
O
O
HO
O
O
O
O
O
SiO2
SiO2
H
H
R
R
1
7
9
8
2
SiO2
R
O
O
O
O
SiO2
-H2O
HO
HO
H2N
N
NH
A
N
B
H
O
O
R
R
11
10
13
3
SiO2
-H2O
N
H2N
NH
N
3
R
R
N
R
O
O
O
HO
N
H
-H2O
H
-H2O
N
N
N
N
N
O
N
H
HN
N
N
N
2
H
4
12
14
1 3

J IRAN CHEM SOC
Table 4 Comparison
result of nano-SiO2 with
Entry
1
Compound
Catalyst/conditions
Time (min)
Yield (%)
H6P2W18O62•18H2O [27],
microwave [28], molecular
iodine (I2) [29], and refluxing in
DMF [30, 31] in the synthesis
1,2,4-triazolo/benzimidazolo
quinazolinone derivatives
4a
H6P2W18O62•18H2O/CH3CN, reflux
Silica gel/microwave
I2/CH3CN, reflux
30
4
95
90
81.2
76
96
91
–
10
–
DMF/reflux
Nano-SiO2/CH3CN, rt
H6P2W18O62.18H2O/CH3CN, reflux
Silica gel/microwave
I2/CH3CN, reflux
30
40
–
2
3
4
5
6
7
4d
4g
4h
6a
6c
6g
–
–
DMF/reflux
–
–
Nano-SiO2/CH3CN, rt
H6P2W18O62•18H2O/CH3CN, reflux
Silica gel/microwave
I2/CH3CN, reflux
15
–
95
–
5
93
82.4
–
10
–
DMF/reflux
Nano-SiO2/CH3CN, rt
H6P2W18O62•18H2O/CH3CN, reflux
Silica gel/microwave
I2/CH3CN, reflux
20
30
5
90
98
96
–
–
DMF/reflux
–
–
Nano-SiO2/CH3CN, rt
H6P2W18O62•18H2O/CH3CN, reflux
Silica gel/microwave
I2/CH3CN, reflux
14
15
3
98
96
95
84.6
65
95
99
94
97.1
53
98
94
92
84.4
–
10
–
DMF/reflux
Nano-SiO2/CH3CN, rt
H6P2W18O62•18H2O/CH3CN, reflux
Silica gel/microwave
I2/CH3CN, reflux
25
10
3
10
–
DMF/reflux
Nano-SiO2/CH3CN, rt
H6P2W18O62•18H2O/CH3CN, reflux
Silica gel/microwave
I2/CH3CN, reflux
20
15
4
10
–
DMF/reflux
Nano-SiO2/CH3CN, rt
20
95
the intermediate 12. Further intermediate 12 undergoes
intra-molecular cyclization by the loss of water molecule to
yield the observed quinazolinones 4 (Scheme 2). The dif-
ference between the routes A and B is in the initial attack
of the nitrogen atom (NH2 or N2). Similarly, the route B
was followed by intermediate 10. The next step, intermedi-
ate 10 reacts with amine sources 3 to afford 14 upon the
loss of water molecule. Further, the intermediate 14 under-
goes intra-molecular cyclization by the loss of water mol-
ecule to give the desired products 4. The mechanism of the
route B is reported by Puligoundla et al. in the presence of
molecular iodine [29]. The proposed mechanism is outlined
in Scheme 2.
This paper describes nano-SiO2 as a heterogeneous,
easy to prepare, inexpensive, and efficient catalyst for the
synthesis of triazoloquinazolinone and benzimidazoquina-
zolinones from readily available aromatic aldehydes, dime-
done, and 2-aminobenzimidazole/3-amino-1,2,4-triazole.
The distinguished advantages of this procedure are no
byproducts, operational simplicity, high yields and the ease
of isolation; hence, no need to column chromatography.
The products were obtained in excellent yields and short
reaction times. Also, ambient conditions were significantly
kinder and milder than the available methods. The present
approach demonstrates a simple and effective method using
nano-SiO2 while a wide range of functional groups can be
1 3

J IRAN CHEM SOC
15. V. Alagarsamy, V.R. Solomon, G. Vanikavitha, V. Paluchamy, M.
Ravichandran, A. Arnaldsujin, A. Thangathirupathy, S. Amuth-
alakshmi, R. Revathi, Biol. Pharm. Bull. 25, 1432 (2002)
16. V. Alagarsamy, G. Murugananthan, R. Venkateshperumal, Biol.
Pharm. Bull. 26, 1711 (2003)
17. V. Alagarsamy, R. Venkatesaperumal, S. Vijayakumar, T. Anga-
yarkanni, P. Pounammal, S. Senthilganesh, S. Kandeeban,
Pharmazie. 57, 306 (2002)
tolerated. Also, the above catalyst was recyclable, cost-
effective, and environment-friendly as well and could be
used in similar reactions.
To show the merit of the this work in comparison with
reported results in the literature, we compared results of
nano-SiO2 with H6P2W18O62•18H2O [27], microwave [28],
molecular iodine (I2) [29], and refluxing in DMF [30, 31] in
the synthesis 1,2,4-triazolo/benzimidazolo quinazolinone
derivatives. As shown in Table 4, nano-SiO2 can act as pro-
ductive and effective catalyst with respect to reaction times
and yields of products.
18. V. Alagarsamy, Pharmazie 59, 753 (2004)
19. V. Alagarsamy, V.R. Solomon, M. Murugan, Bioorg. Med. Chem.
15, 4009 (2007)
20. H. MannJen, H. Li Jiau, K. Sheng Chu, X. Yi Bastow, B. Ken-
neth, N. Y. Hamel, E. Lee, K. Hsiung, J. Med. Chem. 43, 4479
(2000)
21. V. Alagarsamy, R. Revathi, S. Meena, K.V. Ramaseshu, S.
Rajasekaran, E. De Clercq, Indian J. Pharm. Sci. 66, 459 (2004)
22. K.-C. Liu, M.-K. Hu, Arch. Pharm. 319, 188 (1986)
23. T. Eicher, S. Hauptmann, Chemie der Heterocyclen (Georg
Thieme, Stuttgart, New York, 1994), p. 398
Acknowledgments The University of Sistan and Baluchestan is
thanked for supporting this work.
24. V. Haridas, K. Lal, Y.K. Sharma, Tetrahedron Lett. 48, 4719
(2007)
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