One-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones by Fe3O4@SiO2-imid-PMAn nano-catalyst under ultrasonic irradiation and reflux conditions

Article abstract of DOI:10.1007/s00706-016-1832-5

Abstract: Fe₃O₄@SiO₂-imid-PMAⁿ efficiently catalyzes the condensation reaction of isatoic anhydride, aldehydes, and primary amines or ammonium salts to afford the corresponding 2,3-dihydroquinazolin-4(1H)-one derivatives under ultrasonic irradiation or reflux conditions. This method gives notable advantages such as operational simplicity, excellent yields, short reaction times, and absence of any tedious workup or purification. In addition, the excellent catalytic performance and the easy preparation, thermal stability, and separation of the catalyst make it a good heterogeneous system and a useful alternative to other heterogeneous catalysts. Also, the aforementioned nanocatalyst can be easily recovered by a magnetic field and reused for subsequent reactions for at least six times without noticeable deterioration in catalytic activity and reaction yield. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-016-1832-5

Monatsh Chem
DOI 10.1007/s00706-016-1832-5
ORIGINAL PAPER
One-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones
by Fe3O4@SiO2-imid-PMAn nano-catalyst under ultrasonic
irradiation and reflux conditions
Mohsen Esmaeilpour1
Jaber Javidi2,3 Saeed Zahmatkesh4 Nafiseh Fahimi1
•
•
•
Received: 30 April 2016 / Accepted: 4 August 2016
Ó Springer-Verlag Wien 2016
Abstract Fe3O4@SiO2-imid-PMAn efficiently catalyzes
the condensation reaction of isatoic anhydride, aldehydes,
and primary amines or ammonium salts to afford the cor-
responding 2,3-dihydroquinazolin-4(1H)-one derivatives
under ultrasonic irradiation or reflux conditions. This
method gives notable advantages such as operational sim-
plicity, excellent yields, short reaction times, and absence
of any tedious workup or purification. In addition, the
excellent catalytic performance and the easy preparation,
thermal stability, and separation of the catalyst make it a
good heterogeneous system and a useful alternative to
other heterogeneous catalysts. Also, the aforementioned
nanocatalyst can be easily recovered by a magnetic field
and reused for subsequent reactions for at least six times
without noticeable deterioration in catalytic activity and
reaction yield.
Graphical abstract
Keywords 2,3-Dihydroquinazolin-4(1H)-ones Á
Magnetic nanocatalyst Á One-pot synthesis Á
Green synthesis Á Ultrasonic irradiation
Introduction
The development of more efficient and stable catalysts has
been an increasingly important goal for chemists and
material scientists for both economic and environmental
reasons [1]. Homogeneous catalysts show higher catalytic
activities than their heterogeneous counterparts because of
their solubility in reaction media, which increases the
catalytic site accessibility for the substrate [2]. However,
recycling homogeneous catalysts is often tedious and time
consuming and there is also the issue of product contami-
nation observed when these catalysts are used. For
overcoming these drawbacks, metal and organocatalysts
are immobilized on silica-coated Fe3O4 [2, 3]. Magnetic
nanoparticles open up new avenues to introduce an amaz-
ing and efficient system for facilitating catalyst recovery in
organic reactions for the goals of green chemistry [4].
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-016-1832-5) contains supplementary
material, which is available to authorized users.
& Mohsen Esmaeilpour
m1250m551085@yahoo.com
1
Chemistry Department, College of Science, Shiraz
University, Shiraz, Iran
2
Department of Pharmaceutics, School of Pharmacy, Shahid
Beheshti University of Medical Sciences, Tehran, Iran
3
Students Research Committee, School of Pharmacy, Shahid
Beheshti University of Medical Sciences, Tehran, Iran
4
Department of Science, Payame Noor University (PNU),
Tehran, Iran
Recently,
a
number of such functionalized Fe3O4
123

M. Esmaeilpour et al.
nanoparticles have been employed in a range of organic
transformations [5–8].
quinazolinones, Pd-catalyzed heterocyclization of nitroare-
nes, cyclization of o-acylaminobenzamides, preparation
from isatoic anhydrides and Schiff bases, amidation of
2-aminobenzonitrile followed by oxidative ring closure,
Lewis acid-surfactant combined catalysts under aqueous
micellar media and the condensation of isatoic anhydride,
aldehydes, and ammonium acetate or primary amine
[28–34]. Also, recently a number of classical methods for the
synthesis of 2,3-dihydroquinazolin-4(1H)-one have been
reported in literature involving the use of silica sulfuric acid
[33], zinc(II) perfluorooctanoate [29], silica-bonded N-
propylsulfamic acid [35], p-TsOH [36], chiral phosphoric
acid [37, 38], Al(H2PO4)3 [39], Montmorillonite K-10 [40],
gallium triflate [41], nano-Fe3O4 [42], KAl(SO4)2Á12H2O
[34], ionic liquid/water [43], [bimm]BF4 [44], etc. However,
most of the reported methods have certain limitations such as
the use of organic solvents, long reaction times, tedious
processes, harsh reaction conditions and low yields of
product. Thus, developing versatile approaches to synthesize
quinazolinone derivatives still remains a highly desired goal
in organic synthesis.
In recent years, Keggin-type heteropolyacids (HPAs)
such as H3PMo12O40 (PMA) have been used as efficient
catalysts for a variety of organic reactions because of their
superacidic and redox properties, low toxicity, ease of
handling, low cost, high thermal stability, high proton
mobility, water tolerance, recoverability, and reusability
[9]. Although HPAs are versatile compounds in their acidic
form, their main disadvantages are high solubility in polar
solvents and low surface area (\10 m2/g). Therefore, in a
homogeneous reaction, the isolation of the products and the
reuse of the catalyst after reaction become difficult [9].
Therefore, to overcome this problem, these materials dis-
perse on supports (such as silica, acidic ion-exchange
resins, and active carbon) which possess large surface area.
The use of support allows the heteropolyacids to be dis-
persed over a large surface area and increases their
catalytic activity [10].
Developing green procedures is an active area of
research in this direction that have many advantages,
such as being devoid of any carcinogenic effects, lower
cost, reduced pollution, and simplicity in processing,
which are valuable to the industry as well as to the
environment [11]. On the other hand, the use of ultra-
sound irradiation represents a very powerful green
chemical protocol from both the economic and synthetic
point of view [12]. The use of ultrasonic irradiation
accelerates an organic transformation at ambient condi-
tions, which otherwise require harsh conditions of
temperature and pressure [13]. The interaction between
molecules and ultrasound is not direct, but the energy of
these long wavelength can cause cavitation which makes
the reaction faster [14].
Therefore, as a result of our great interest in the
application of magnetic catalysts in organic reactions
[45–49], herein we describe a convenient, simple, and
practical procedure for the synthesis of mono- and dis-
ubstituted
2,3-dihydroquinazolin-4(1H)-ones
by
employing isatoic anhydride, aldehydes, and amines or
ammonium salts in the presence of Fe3O4@SiO2-Imid-
PMAn magnetic nanocatalyst in one pot under ultrasonic
irradiation or reflux conditions. Figure 1 represents the
procedure for the preparation of Fe3O4@SiO2-imid-
PMAn step by step.
One of the most frequently encountered heterocycles in
medicinal chemistry is quinazolinone derivatives with wide
applications including anticancer [15], antihypertensive
[16], antidiuretic [17], anticonvulsant [18], antibacterial
[19], antihistaminic [20], antidiabetic [21], and anti-in-
flammatory [22] activities.
Results and discussion
In continuation of our investigations on the use of super-
paramagnetic catalysts for the fine chemical preparation
[2, 50], here one-pot condensation of primary amines or
ammonium salts and aromatic aldehydes with isatoic
anhydride in the presence of Fe3O4@SiO2-imid-PMAn is
reported (Scheme 1).
2,3-Dihydroquinazoline derivatives are a class of hete-
rocycles which exhibit biological and pharmaceutical
activity and herbicidal agents, as well as plant growth
regulators [23]. Also, these compounds can be easily oxi-
dized to their quinazolin-4(3H)-one analogs [24], which are
among the most important biologically active heterocyclic
compounds and can be found in some natural products
[25–27].
In a preliminary study, the reaction of benzaldehyde and
aniline with isatoic anhydride was chosen as a model
reaction to optimize the reaction conditions. As shown in
Table 1, the model reaction was refluxed in the presence of
0.04 g of Fe3O4@SiO2-imid-PMAn and a variety of sol-
vents such as ethanol, dichloromethane, acetonitrile, ethyl
acetate, toluene, THF, water and in solvent-free conditions
(Table 1, entries 1–11). The represented data in Table 1
shows that the reaction proceeded efficiently in refluxing
H2O/EtOH [1:3(v/v)] and resulted in high yields of the
desired product (Table 1, entry 11).
In view of these useful properties, various procedures
have been reported for preparing 2,3-dihydroquinazolin-
4(1H)-ones in literature, which include reduction of the azide
functionality, the condensation reaction of anthranilamide
with aldehyde or ketone, desulfurization of 2-thioxo-4(3H)-
123

One-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones by Fe3O4@SiO2-imid-PMAn…
Fig. 1 Preparation and
characterization of
Fe3O4@SiO2-imid-PMAn
Then, we also briefly examined the effect of different
temperatures and the amount of catalyst. The effect of tem-
perature was studied by carrying out the model reaction at
different temperaturesinH2O/EtOH [1:3(v/v)]inthe presence
of Fe3O4@SiO2-imid-PMAn (room temperature, 60 °C, and
reflux; Table 1, entries 11, 17, 18) and the best result was
obtained under reflux conditions (Table 1, entry 11).
To elucidate the role of the catalyst, at first, we found
that in the absence of the catalyst, the yield was poor even
for longer time (Table 1, entry 12). Fe3O4@SiO2-imid-
PMAn proved to be a superior catalyst among all the cat-
alysts screened in this transformation. It should be noted
that 0.04 g of catalyst was efficient enough to catalyze the
reaction under reflux conditions in H2O/EtOH [1:3 (v/v)]
123

M. Esmaeilpour et al.
Scheme 1
Table 1 Optimization of different proportions of Fe3O4@SiO2-imid-PMAn and also the effect of solvents and temperature on the reaction of
isatoic anhydride, benzaldehyde, and aniline
Entry
Solvent
Catalyst amount/g
Condition
Time/h
Yield/%a
1
Solvent-free
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
0.04
None
0.01
0.02
0.03
0.05
0.04
0.04
0.03
0.03
0.03
0.03
0.03
None
0.01
0.02
0.025
0.035
90 °C
Reflux
2
77
85
51
67
57
79
43
63
78
68
89
18
38
72
83
88
41
62
89
82
74
92
73
12
55
68
90
88
2
EtOH
2
3
CH2Cl2
Reflux
2
4
CH3CN
Reflux
2
5
EtOAc
Reflux
2
6
Toluene
Reflux
2
7
THF
Reflux
2
8
H2O
Reflux
2
9
H2O/EtOH = [1:1(v/v)]
H2O/EtOH = [3:1(v/v)]
H2O/EtOH = [1:3(v/v)]
H2O/EtOH = [1:3(v/v)]
H2O/EtOH = [1:3(v/v)]
H2O/EtOH = [1:3(v/v)]
H2O/EtOH = [1:3(v/v)]
H2O/EtOH = [1:3(v/v)]
H2O/EtOH = [1:3(v/v)]
H2O/EtOH = [1:3(v/v)]
H2O/EtOH = [1:3(v/v)]
H2O/EtOH = [1:1(v/v)]
H2O/EtOH = [3:1(v/v)]
EtOH
Reflux
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Reflux
2
Reflux
2
Reflux
24
3
Reflux
Reflux
3
Reflux
2
Reflux
2
R.T
12
3
60 °C
Sonication (40 kHz)/r.t
Sonication (40 kHz)/r.t
Sonication (40 kHz)/r.t
Sonication (40 kHz)/r.t
Sonication (40 kHz)/r.t
Sonication (40 kHz)/r.t
Sonication (40 kHz)/r.t
Sonication (40 kHz)/r.t
Sonication (40 kHz)/r.t
Sonication (40 kHz)/r.t
0.42
0.50
0.50
0.17
0.50
1
H2O
EtOH
EtOH
0.50
0.33
0.33
0.17
EtOH
EtOH
EtOH
Reaction conditions: isatoic anhydride (1 mmol), benzaldehyde (1 mmol), aniline (1.2 mmol), 4 cm3 solvent
a
Isolated yield
(Table 1, entry 11), and increasing the amount of catalyst
did not improve the yield significantly (Table 1, entry 16).
On the other hand, decreasing the catalyst concentration
resulted in lower yields under the same conditions
(Table 1, entries 13–15). Also, to improve the yields, we
performed reactions using different quantities of reagents.
123

One-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones by Fe3O4@SiO2-imid-PMAn…
Table 2 Fe3O4@SiO2-imid-PMAn catalyzed the synthesis of mono- and disubstituted derivatives of 2,3-dihydroquinazolin-4(1H)-one
Entry
R1
R2NH2 or (NH4)?X-
Method Aa
Method Bb
Product
M.p./°C
Time/h
Yield/%c
Time/min
Yield/%c
1
C6H5
CH3CH2
1.5
2
88
87
91
92
81
84
89
85
86
81
80
88
90
88
91
91
89
92
87
93
90
93
95
92
93
87
85
90
88
82
84
80
78
81
86
83
79
76
80
77
85
5
10
5
94
88
89
94
86
90
92
91
87
84
82
88
93
90
89
92
93
87
91
95
88
94
93
91
94
87
83
94
91
90
84
86
83
89
92
85
78
81
87
80
92
1a
1b
1c
1d
1e
1f
135–137 (134–137 [37])
134–136 (132–135 [37])
158–160 (160–161 [37])
175–177 (176–178 [37])
178–180 (180–182 [54])
123–125 (124–126 [37])
203–205 (205–206 [29])
213–215 (214–217 [54])
184–186 (186–188 [54])
194–196 (195–196 [29])
193–195 (194–196 [29])
202–204 (204–205 [29])
163 (164–165 [37])
2
p-ClC6H4
CH3CH2
3
p-O2NC6H4
m-O2NC6H4
p-HOC6H4
p-CH3OC6H4
C6H5
CH3CH2
1
4
CH3CH2
1.5
2.5
2.5
2
8
5
CH3CH2
25
20
10
15
18
25
15
12
15
10
18
30
35
30
24
10
18
20
8
6
CH3CH2
7
C6H5
1g
1h
1i
8
p-ClC6H4
C6H5
2.5
2
9
m-O2NC6H4
p-O2NC6H4
m-CH3C6H4
p-CH3OC6H4
C6H5
C6H5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
a
C6H5
3
1j
C6H5
2.5
3
1k
1l
C6H5
CH3
1.5
1.5
1.5
2.0
2.5
3.0
4
1m
1n
1o
1p
1q
1r
1s
p-ClC6H4
CH3
187–188 (188–190 [37])
145–147 (145–146 [37])
185–187 (184–186 [55])
227–229 (225–230 [55])
226–227 (225–226 [56])
150–152 (148–151 [29])
247–249 (246–248 [56])
273–275 (275 [56])
p-CH3OC6H4
p-CH3OC6H4
o-CH3OC6H4
2,5-(CH3O)2C6H3
CH3(CH2)5
2,3-(Cl)2C6H3
o-CH3OC6H4
2,5-(CH3O)2C6H3
p-O2NC6H4
C6H5
CH3
Benzothiazolyl
Benzothiazolyl
Benzothiazolyl
Benzothiazolyl
Benzothiazolyl
Benzoimidazolyl
Benzoimidazolyl
Benzoimidazolyl
1.5
2.5
3.0
2.5
2
1t
1u
1v
1w
2a
2b
2c
2d
2e
2f
234–236 (235 [56])
[300 ([300 [56])
2-
CO3
16
12
30
40
25
16
12
10
30
30
14
26
18
10
30
25
50
28
219–221 (218–220 [57])
196–197 (198–200 [57])
232–233 (233–234 [40])
163–165 (165–167 [40])
180–181 (178–180 [57])
167–168 (165–167 [40])
218–219 (218–220 [57])
197–198 (198–200 [57])
231–233 (233–234 [40])
165–166 (165–167 [40])
179 (178–180 [58])
2-
CO3
p-ClC6H4
2
2-
CO3
p-CH3C6H4
o-CH3OC6H4
p-CH3OC6H4
2-Furanyl
3
2-
CO3
2
2-
CO3
4
2-
CO3
2.5
2
C6H5
AcO-
AcO-
AcO-
AcO-
AcO-
AcO-
Cl-
Cl-
Cl-
Cl-
Cl-
2g
2h
2i
p-ClC6H4
3
p-CH3C6H4
o-CH3OC6H4
p-CH3OC6H4
2-Furanyl
4
2.5
3.5
2.5
2
2j
2k
2l
166–167 (165–167 [40])
217–218 (218–220 [57])
198 (198–200 [57])
C6H5
2m
2n
2o
2p
2q
2r
p-ClC6H4
3
p-CH3C6H4
o-CH3OC6H4
p-CH3OC6H4
2-Furanyl
3.5
2.5
4
232–234 (233–234 [40])
164–165 (165–167 [40])
179–181 (178–180 [57])
167–169 (165–167 [40])
Cl-
2.5
Reaction conditions: isatoic anhydride (1 mmol), primary amine (1.2 mmol), or ammonium salts (ammonium acetate 1.2 mmol, ammonium
carbonate 0.6 mmol, or ammonium chloride 1.2 mmol), aldehyde (1 mmol), 0.04 g Fe3O4@SiO2-imid-PMAn, 4 cm3 H2O/EtOH [1:3 (v/v)],
reflux
b
Reaction conditions: isatoic anhydride (1 mmol), primary amine (1.2 mmol) or ammonium salts (ammonium acetate 1.2 mmol, ammonium
carbonate 0.6 mmol, or ammonium chloride 1.2 mmol), aldehyde (1 mmol), 0.03 g Fe3O4@SiO2-imid-PMAn, 4 cm3 EtOH, ultrasonic irradi-
ation, rt
c
Isolated yields
123

M. Esmaeilpour et al.
The best result was obtained with 1:1:1.2 ratios of ben-
zaldehyde, isatoic anhydride, and aniline in the presence of
0.04 g of magnetic catalyst. Therefore, we employed the
optimized conditions for the preparation of mono- and
disubstituted 2,3-dihydroquinazolin-4(1H)-ones.
H2O/EtOH [1:3 (v/v)] and ultrasonic irradiation in EtOH.
A series of aromatic aldehydes carrying either electron-
releasing or electron-withdrawing substituents afforded
high yields of products (Table 2). The substitution
groups on the aromatic ring had no obvious effect on the
yield. Several aliphatic and aromatic amines were used
for this reaction. Aliphatic amines afforded the products
in shorter time compared to aromatic analogs (Table 2,
entries 1–15).
Considering the ability of ultrasonic irradiation for the
acceleration of organic reactions, we examined the model
reaction under ultrasonic irradiation at room temperature in
the presence of various solvents and various amounts of
catalyst. As it is clear from Table 1, the best results were
obtained in the presence of 0.03 g of catalyst in EtOH
(Table 1, entry 22). Compared with conventional heating,
the reaction catalyzed by Fe3O4@SiO2-imid-PMAn under
ultrasonic irradiation showed a more effective catalytic
activity. Obviously, ultrasound irradiation could accelerate
the reaction and the chemical effects of ultrasounds resul-
ted from implosive collapse of the cavitation period of the
sound waves [51–53].
We also have introduced an efficient and environmen-
tally friendly approach for the synthesis of heterocyclic
compounds via the three-component condensation reaction
of isatoic anhydride and aromatic aldehydes with
2-aminobenzothiazole or 2-aminobenzimidazole under
optimized conditions in good yields (Table 2, entries
16–23).
To compare the efficiency of ammonium salts in the
synthesis of 2,3-dihydroquinazolin-4(1H)-ones, the reac-
tions were carried out using ammonium carbonate, acetate,
and chloride under the same reaction conditions. In all
cases, monosubstituted 2,3-dihydroquinazolin-4(1H)-ones
were produced in good yields (Table 2, entries 24–41).
Moreover, it is clear that, under the same reaction condi-
tions, reactions under ultrasonic irradiation led to shorter
reaction times.
Following the obtained results, other derivatives of
2,3-dihydroquinazolin-4(1H)-one were synthesised using
different types of amines or ammonium salts and alde-
hydes under the optimized conditions. The results are
summarized in Table 2. As expected, disubstituted
derivatives of 2,3-dihydroquinazolin-4(1H)-one were also
afforded in good to excellent yields under both refluxing
Table 3 Reaction of isatoic anhydride, aniline, and benzaldehyde using different acid catalysts
Entry
Catalyst
Conditions
Time/h
Yield/%a
References
1
2
3
4
Montmorillonite K-10
Zn(PFO)2
EtOH/reflux
6.5
6
80
82
80
78
65
79
84
80
82
85
80
79
65
83
25
36
82
89
81
92
[40]
[29]
[30]
[34]
H2O/EtOH [1/3 (v/v)]/reflux
EtOH/reflux
Silica sulfuric acid
KAl(SO4)2Á12H2O
6.5
4
EtOH/reflux
H2O/reflux
1
5
6
7
8
9
Ga(OTf)3
EtOH/reflux
1
[41]
[58]
[45]
[28]
[59]
b-Cyclodextrin
[bmim]BF4
Copolymer-PTSA
SSA
H2O/reflux
3
Solvent-free/70 °C
EtOH/reflux
1.5
6.5
4.5
5
H2O/80 °C
Solvent-free/80 °C
H2O/reflux
10
p-TsOH
2.5
6.5
1.5
2
[23]
EtOH/reflux
11
12
13
14
15
16
17
Dodecylbenzenesulfonic acid
Silicasulfuric acid
Ultrasound irradiation/H2O/rt
Ultrasound irradiation/H2O/rt
EtOH/reflux
[60]
[60]
Fe3O4@SiO2 (0.04 g)
8
This work
This work
This work
This work
This work
Fe3O4@SiO2-imid-PMAb (0.04 g)
Fe3O4@SiO2-imid-PMAn (0.04 g)
Fe3O4@SiO2-imid-PMAb (0.03 g)
Fe3O4@SiO2-imid-PMAn (0.03 g)
H2O/EtOH [1:3(v/v)]/reflux
H2O/EtOH [1:3(v/v)]/reflux
Ultrasound irradiation/EtOH/rt
Ultrasound irradiation/EtOH/rt
3
2
0.17
0.17
Reaction of isatoic anhydride, benzaldehyde, and aniline using different catalysts
b bulk, n nano
a
Yields refer to isolated pure product
123

One-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones by Fe3O4@SiO2-imid-PMAn…
Scheme 2
To compare the reactivity of the Fe3O4@SiO2-imid-
PMAn with the previously reported catalysts, a compara-
tive chart is presented in Table 3. In comparison with the
other reported catalysts in literature, we observed that the
Fe3O4@SiO2-imid-PMAn gives better yield in shorter
reaction time than another catalyst (Table 3). Also, ana-
lyzing the reactions on catalysts such as Fe3O4@SiO2 and
Fe3O4@SiO2-imid-PMAb under both refluxing H2O/EtOH
[1:3(v/v)] and ultrasonic irradiation lead to lower yields
and long times to produce the desired products (Table 3,
entries 13, 14, 16).
the aldehydes. Subsequently, the reaction of activated
aldehyde with I proceeds to afford intermediate II that is
converted to product III via an intramolecular cyclization.
A series of catalytic cycles were run to investigate the
stability of the catalyst. In each case, the catalyst was
recovered by an external magnetic field, followed by
rinsing with hot ethanol, dried at 70 °C for 2 h and reused
for subsequent reactions. In each cycle, the reaction was
performed under the optimized conditions.
The key feature of the magnetically separable catalysis
is the reusability of the catalyst. The recyclability of the
catalyst was investigated using a model reaction between
isatoic anhydride, benzaldehyde, and aniline in the pres-
ence of the Fe3O4@SiO2-imid-PMAn catalyst under
refluxing H2O/EtOH [1:3 (v/v)] and ultrasonic irradiation
in ethanol. As shown in Fig. 2a, limited decline in the
catalytic activity of the catalyst was observed after six
cycles.
The plausible general mechanistic pathway is shown in
Scheme 2. First, the isatoic anhydride is activated with
Fe3O4@SiO2-imid-PMAn by the formation of hydrogen
bonding with the carbonyl group followed by nucleophilic
attack of amine on the carbonyl group, and then
anthranilamide I could be produced with the liberation of
carbon dioxide.
Fe3O4@SiO2-Imid-PMAn act as Bronsted acid and play
The amounts of the nano heteropolyacid leaching for the
reactions under the optimized conditions were detected.
a significant role in increasing the electrophilic character of
123

M. Esmaeilpour et al.
Fig. 2 a Recyclability of Fe3O4@SiO2-imid-PMAn in the synthesis
of 1g under the optimized conditions. b PMAn leaching in each
reaction cycle. c The FT-IR spectrum of the fresh and reused catalyst.
d SEM and DLS images of Fe3O4@SiO2-imid-PMAn nanoparticles
after six reaction cycles. e Photo images of magnetic field response of
Fe3O4@SiO2-imid-PMAn nanoparticles
The molybdenum (Mo) amount in the reaction medium
after each reaction cycle was measured through ICP and
the details are shown in Table 2b. The analysis of the
reaction mixture by the ICP technique showed that the
leaching of H3PMo12O40 was negligible.
stable suspension. As shown in Fig. 2e, by applying an
external magnet to the side wall of a sealed vessel, the
catalyst was magnetically separated from the solution
(Fig. 2e).
Figure 2c shows the FT-IR spectra of the fresh and
reused catalyst. The presence of vibration bands at 556,
Conclusion
794, 864, 956, 1055, 1095, 1454, and 2790–2985 cm-1
,
which is due to the Fe–O, Mo–Oe–MO, Mo–Oc–MO, Mo–
Ot, P–O, Si–O–Si, C=N, and CH, respectively, demon-
strates the existence of Fe3O4@SiO2-imid-PMAn in the
spectrum (Fig. 2c). This clearly indicated the presence of
nano H3PMo12O40 on the silica support even after the
reaction.
In conclusion, we have reported an efficient catalyst for the
synthesis of quinazolinone derivatives by the three-com-
ponent one-pot condensation of isatoic anhydride with
amines or ammonium salt and aldehydes under ultrasonic
irradiation or reflux conditions. The present method offers
several advantages including easy recovery and reuse of
catalyst by magnetic field, short reaction time, high yields,
ease of workup, and use of cheap and commercially
available starting materials. We believe that many biolog-
ically active derivatives could be synthesised by this multi-
component reaction with high atomic economy. Moreover,
the catalyst used is easily recovered by the external mag-
netic field and reused without any noticeable loss of
activity after at least six times.
SEM and DLS images of the catalyst after the six
recycle have been represented in Fig. 2d. As shown in
Fig. 2d, Fe3O4@SiO2-imid-PMAn nanospheres had an
average diameter of 80 nm, were of uniform size, and
showed good dispersity. Additionally, the hydrodynamic
diameter of the catalyst was investigated by the DLS
technique (Fig. 2d). This size distribution is centered at a
value of 75 nm. Generally, the size of the catalysts will be
increased after each cycle and leaching of H3PMo12O40 and
increasing of catalyst size lead to decreases in the yield.
The theoretical curve of standard distribution from our
studies was calculated by means of Microsoft Excel.
Besides its high catalytic capacity and stability, a
noticeable feature of the catalyst was that it could be easily
separated from the solution with a magnet and showed no
Experimental
All chemicals were commercially available and used
without further purification. The NMR spectra were
recorded on a Bruker Avance DPX 500 MHz spectrometer
in chloroform (CDCl3) using tetramethylsilane (TMS) as
tendency to self-aggregation, thus forming
a
123

One-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones by Fe3O4@SiO2-imid-PMAn…
an internal reference. Fourier transform infrared (FT-IR)
spectra were obtained using a Shimadzu FT-IR 8300
spectrophotometer. Dynamic light scatterings (DLS) were
recorded on a HORIBA-LB550. Scanning electron micro-
scopy (SEM) image was obtained on Philips XL-30ESEM.
Melting points were obtained in open capillary tubes and
measured on an electrothermal 9200 apparatus. Mass
spectra were obtained at 70 eV. The C, H, N, and S ele-
mental analyses were carried out by using a Thermofinigan
Flash EA-1112 CHNSO rapid elemental analyzer. Soni-
cation was performed using an ultrasound cleaning bath
(KQ-250B, China) with a frequency of 40 Hz and voltage
of 220 V. All yields refer to the isolated products. There-
(PMAb) was dispersed in 50 cm3 n-octane and the
resulting dispersion was stirred vigorously for 30 min at
room temperature to form a homogeneous dispersion.
This dispersion was transferred into a Teflon-lined stain-
less autoclave filling 80 % of the total volume. The
autoclave was sealed and maintained at 150 °C for 12 h.
The autoclave was then cooled to room temperature.
Finally, the resulting powder was filtered and washed for
several times by octane and dried in a vacuum at 80 °C
for 12 h.
In the last step, 1.0 g Fe3O4@SiO2-Imid was added to a
solution of PMAn (1.0 mmol) in 20 cm3 was taken in a
round-bottom flask. The mixture was refluxed for 24 h
under a nitrogen atmosphere. After 24 h, the mixture was
filtered by an external magnet, washed with acetonitrile
and dichloromethane, and dried at 70 °C for 6 h. FT-IR
spectrum of the catalyst showed the expected bands,
including distinctive bands due to anchoring of PMAn onto
Fe3O4@SiO2-imid.
1
fore, all of the products were characterized by FT-IR, H
NMR and 13C NMR, and also by comparison with
authentic samples.
Preparation of Fe3O4@SiO2-imid-PMAn
The catalyst (Fe3O4@SiO2-Imid-PMAn) was synthesized
by the reported procedure [50]. Briefly, firstly Fe3O4@SiO2
core–shell was prepared by the coprecipitation method.
The mixture of 1.3 g FeCl3Á6H2O (4.8 mmol) in 15 cm3
water was added to the solution of polyvinyl alcohol (PVA
15000), as a surfactant, and 0.9 g FeCl2Á4H2O (4.5 mmol)
in 15 cm3 water, which was prepared by completely
dissolving PVA in water followed by the addition of
FeCl2Á4H2O. The resultant solution was left to be stirred
for 30 min at 80 °C. Then, hexamethylenetetramine
(1.0 mol/dm3) was added dropwise with vigorous stirring
to produce a black solid product when the reaction media
reached pH 10. The resultant mixture was heated on a
water bath for 2 h at 60 °C and the black magnetite solid
product was separated and washed with ethanol three times
and then dried at 80 °C for 10 h. Then, 0.50 g Fe3O4
nanoparticle (2.1 mmol) was dispersed in the mixture of
50 cm3 ethanol, 5 cm3 deionized water, and 0.20 cm3
tetraethoxysilane, followed by the addition of 5.0 cm3 of
NaOH (10 wt%). This solution was stirred mechanically
for 30 min at room temperature. Then the product,
Fe3O4@SiO2, was separated by an external magnet and
was washed with deionized water and ethanol three times
and dried at 80 °C for 10 h.
General procedure for the synthesis of mono- and
disubstituted derivatives of 2,3-dihydroquinazolin-
4(1H)-one
A mixture of isatoic anhydride (1 mmol), ammonium salt
(ammonium acetate 1.2 mmol, ammonium carbonate
0.6 mmol, or ammonium chloride 1.2 mmol) or primary
amine (1.2 mmol), aldehyde (1 mmol) and 0.04 g (reflux)
or 0.03 g (ultrasonic) Fe3O4@SiO2-imid-PMAn catalyst in
4 cm3 H2O/EtOH [1:3 (v/v)] was refluxed in an oil bath or
sonicated at room temperature in 4 cm3 ethanol for an
appropriate time as mentioned in Table 2. After the
completion of the reaction, as monitored by TLC [eluent:
petroleum ether:ethyl acetate: 4:1 (v/v)], the catalyst was
separated using a magnetic field and the residue was
concentrated to afford the crude product. Finally, the crude
product was recrystallized from ethanol.
Acknowledgments The authors are grateful to the council of the Iran
National Science Foundation and University of Shiraz for their
unending effort to provide financial support to undertake this work.
References
In the second step, Fe3O4@SiO2-imid was synthesized.
Fe3O4@SiO2 (1 g) was added to the solution of 0.241 g
3-chlorotriethoxypropylsilane (1 mmol) and 0.0680 g imi-
dazole (1 mmol) in 20 cm3 p-xylene and the resultant
mixture was under reflux for 24 h under a nitrogen atmo-
sphere. After refluxing for about 24 h, the mixture was
cooled to room temperature, filtered by an external magnet,
and the product was washed with xylene to remove any
reacted species and dried at 70 °C for 6 h.
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