Ultrasonic assisted synthesis of 2, 3-dihydroquinazolin-4(1H)-ones involving three-component reaction of isatoic anhydride, amines and pyrazole carbaldehydes catalyzed by [?-fe2o3?hap-So3H]

Article abstract of DOI:10.2174/1570178616666190401183953

The combination of [?-Fe₂O₃?HAp-SO₃H] as a catalyst and ultrasonic effect catalyzed the synthesis of diverse derivatives of 2, 3-dihydroquinazolin-4(1H)-ones which is reported in this study. The products were synthesized via the one-pot three-component reaction of isatoic anhydride, amines and pyrazole carbaldehydes in water: EtOH catalyzed by recoverable [?-Fe₂O₃?HAp-SO₃H]. This paper conducted an investigation of the effect of various solvents, temperatures and catalysts on the reactions. Short reaction times, mild reaction conditions, simple work-up, the desired yields and the use of an appropriate catalyst are the advantages of this novel method. The new derivatives were validated by using FT-IR,¹HNMR, and¹³CNMR. Moreover, the synthesized compounds were screened for their an-timicrobial activity against bacterial strains.

Full text of DOI:10.2174/1570178616666190401183953

24
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Letters in Organic Chemistry, 2020, 17, 24-30
LETTER ARTICLE
ISSN: 1570-1786
eISSN: 1875-6255
Ultrasonic Assisted Synthesis of 2, 3-Dihydroquinazolin-4(1H)-ones Involv-
ing Three-Component Reaction of Isatoic Anhydride, Amines and Pyra-
zole Carbaldehydes Catalyzed by [Ɣ-Fe2O3@HAp-SO3H]
Impact
Factor:
0.723
BENTHAM
S
CIENCE
Kiana F. Sina1, Asieh Yahyazadeh1,*, Nosrat O. Mahmoodi1, Kurosh R. Moghadam1,
Mohammad Nikpassand2 and Mahdi Rasa1
2
1Department of Chemistry, Faculty of Sciences, University of Guilan, PO Box 41335-1914, Rasht, Iran; Department of
Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
Abstract: The combination of [Ɣ-Fe2O3@HAp-SO3H] as a catalyst and ultrasonic effect catalyzed the
synthesis of diverse derivatives of 2, 3-dihydroquinazolin-4(1H)-ones which is reported in this study.
The products were synthesized via the one-pot three-component reaction of isatoic anhydride, amines
A R T I C L E H I S T O R Y
and pyrazole carbaldehydes in water: EtOH catalyzed by recoverable [Ɣ-Fe2O3@HAp-SO3H]. This pa-
per conducted an investigation of the effect of various solvents, temperatures and catalysts on the reac-
tions. Short reaction times, mild reaction conditions, simple work-up, the desired yields and the use of
Received: October 08, 2018
Revised: March 10, 2019
Accepted: March 12, 2019
DOI:
an appropriate catalyst are the advantages of this novel method. The new derivatives were validated by
10.2174/1570178616666190401183953
using FT-IR, 1HNMR, and 13CNMR. Moreover, the synthesized compounds were screened for their an-
timicrobial activity against bacterial strains.
Keywords: 2, 3-Dihydroquinazolinone, pyrazole carbaldehydes, ultrasonic, [Ɣ-Fe2O3@HAp-SO3H], catalyst, one-pot three-
component reaction.
1. INTRODUCTION
large amount of hazardous organic and natural solvents
makes it a proper replacement for previously applied proce-
dures [5]. We would like to report a one-pot reaction for
2, 3-dihydroquinazoline-4(1H)-ones from isatoic anhydride,
pyrazole carbaldehydes (Table 4) and amine (such as ammo-
nium acetate, ammonium carbonate, aniline, 4-methyl aniline,
4-ethoxy aniline, 4-chloro aniline) using [Ɣ-Fe2O3@HAp-
SO3H] as a nanocatalyst under ultrasonic Scheme 1.
Heterocycles has acquired a central position in organic
and natural chemistry [1]. Nitrogen-containing heterocycles
are a basic part of many drug compounds, physiologically
active natural products and synthetic molecules [2]. Quina-
zolin-4-ones are essential fused heterocycles which were
found to have useful biological and pharmacological activi-
ties involving antifungal, analgesic, antidiabetic, antitumor,
antibacterial, anticonvulsant and antihypertensive [3].
Among quinazolinones, 2, 3-dihydroquinazoline-4(1H) ones
are attractive forms. In 2015, we examined a one-pot three
components reaction between isatoic anhydride, ammonium
acetate and pyrazole carbaldehydes in the presence of
[BDBIm]Br under microwave irradiation [4]. We were inter-
ested in developing these reactions by using the ultrasound
method with various amines in the presence of an acid nano-
catalyst. [Ɣ-Fe2O3@HAp]-supported dual acidic nanocatalyst
is known as a novel, heterogeneous and reusable catalyst.
This catalyst was used in the reaction to be performed in
mild conditions, with good yields, low cost and short reaction
times. An environmentally friendly and inexpensive catalyst
that requires a fairly easy work-up procedure without using a
2. RESULTS AND DISCUSSION
Firstly, as a model reaction, the one-step reaction of (1
mmol) isatoic anhydride, (0.6 mmol) ammonium carbonate
and (1 mmol) pyrazole carbaldehyde in water: ethanol under
ultrasound irradiation using [Ɣ-Fe2O3@HAp-SO3H] was
investigated under diverse conditions. The reactions were
performed in pure water, EtOH, H2O: EtOH (1:1), H2O:
EtOH (3:1) and H2O: EtOH (1:3) (Table 1). We were ob-
served using H2O: EtOH (3:1) as a solvent which obtained
the best yield [6, 7]. Also, the reactions were carried out in
different temperatures such as at 40°C, 50°C, and 60°C)
under sonication. It was found that increasing the reaction
temperature improved the vapor pressure of the solvent and
built up cavitation which further accelerated the reaction [8].
Thus, we preferred to use (1 mmol) isatoic anhydride,
(1mmol) pyrazole carbaldehyde, (0.6 mmol) ammonium
*Address correspondence to this author at the Department of Chemistry,
Faculty of Sciences, Guilan University, P.O. Box: 41335-1914, Rasht, Iran;
Tel/Fax: +98-013-33343630; E-mail: yahyazadeh@guilan.ac.ir
1875-6255/20 $65.00+.00
© 2020 Bentham Science Publishers

Ultrasonic Assisted Synthesis of 2, 3-Dihydroquinazolin-4(1H)-ones
Letters in Organic Chemistry, 2020, Vol. 17, No. 1 25
R2
N
O
H
N
N
(NH4)nX
N
N
O
[γ-Fe2O3@HAp-SO3H]
or
+
+
N
)))). 60°C
H2O: EtOH (3:1)
N
H
O
NH2R1
R1 Or H
CHO
O
R2
R1 = C6H5 , 4-Me C6H4, 4-OEt C6H4, 4-Cl C6H4
R2 = H, OH, Cl, OMe
X = OAc-, CO3
2-
n = 1, 2
Scheme (1). Synthesis of 2, 3-dihydroquinazolin-4(1H)-ones catalyzed by [Ɣ-Fe2O3@HAp-SO3H].
Table 1. Optimization of the solvent for the synthesis of 2, 3-dihydroquinazolin-4(1H)-ones.
Entry
Solvent
Time (h)
Yield (%)
1
2
3
4
5
EtOH
2
1
1
2
1
60
62
84
72
90
Pure water
H2O: EtOH 1:1
H2O: EtOH 1:3
H2O: EtOH 3:1
carbonate1 and 10 mg catalyst in water: ethanol (3:1) at
60°C as the best choice for synthesizing 2, 3-
dihydroquinazoline-4(1H)-ones [9]. To show the advan-
tages of [Ɣ-Fe2O3@HAp-SO3H], compared to K10, nano-
Fe3O4, Cu(OAc)2, p-TsOH, and iodine (Table 2). The re-
sulting product was obtained in the yield of 82%, 87%,
79%, 71%, 85%, and 92%. Also, some reactions were exam-
ined in the absence of a catalyst (Table 3). It was proven that
[Ɣ-Fe2O3@HAp-SO3H] is a powerful catalyst for the activa-
tion of the substrates and intermediates in the direction of the
reaction [10].
vacuum and reused in the next run. The results showed that
the activity of the nanocatalyst remained unchanged for four
consecutive runs [5, 13].
The application of ultrasound is popular as a profitable
tool in synthesis, also improving the green methods and or-
ganic reactions. Sonication speeds up the reaction by produc-
ing a driving energy by cavitation, and by the creation and
collapse of bubbles, thereby, increasing the rate and selectiv-
ity [12]. Ultrasound can have special physical and chemical
effects on the reaction. Similar experiments were carried out
with stirring under refluxing conditions. It was found that the
reactions under refluxing demanded longer reaction times
and resulted in lower yields (Table 3) [8].
To expand the efficiency of the process, this catalyzed
reaction was combined with ultrasound [11]. The prepared
pyrazole carbaldehydes and also amine derivatives or am-
monium salts were used to synthesize the related products in
good yields.
Based on our test results and also other reported mecha-
nisms in the literature, the suggested mechanism of the reac-
tion is recommended in Scheme 2. The interaction of the
nanocatalyst and isatoic anhydride forms a reactive interme-
diate (I), then, the N- nucleophilic primary amine attacks on
the carbonyl unit of I to form an intermediate (II). Decar-
boxylation reaction and proton transfer produce an interme-
diate (III). Subsequently, the reaction of an activated alde-
hyde with III gives H2O to form an imine intermediate (IV).
In the presence of the nanocatalyst, the amide functional
group in intermediate (IV) could be formed by the tautomer-
ism phenomenon (V). Thus, the intermolecular nucleophilic
attack of the amide nitrogen on the activated imine carbon
provides an intermediate (VI). Finally, 1,5-proton transfer
produces the desired product [10, 16].
The results demonstrate the high potential of this novel
strategy such as low cost, good yields, short reaction times,
the use of a simple recoverable catalyst and easy work-up for
the synthesis of substituted 2, 3-dihydroquinazoline-4(1H)-
ones. The structures of the products were confirmed by FT-
IR, 1HNMR and 13CNMR spectroscopy [12].
To examine the recyclability of the catalyst, the nano-
catalyst was separated from the product by attaching an ex-
ternal magnetic field, washed with diethyl ether, dried under
1Ammonium carbonate (0.6 mmol) contains 1.2 mmol ammonium ion.

26 Letters in Organic Chemistry, 2020, Vol. 17, No. 1
Sina et al.
Table 2. Effect of the catalysts in the reaction of isatoic anhydride, ammonium carbonate and 1, 3-diphenyl-1H-pyrazole-4-
carbaldehyde.
Entry
Catalysta
Time (h)
Yield (%)b
1
2
3
4
5
6
K10
Nano-Fe3O4
Cu(OAc)2
2
1.5
3
82
87
79
71
85
92
p-TsOH
5
Iodine
2.5
[Ɣ-Fe2O3@HAp-SO3H]
1
aAmount of catalyst used for entries: 1 (5% w/w) [11], 2 (15 mol%) [14], 3 (0.05 g), 4 (10 mol%) [5], 5 (5 mol%) [15], 6 (10 mg = 0.9 mol %) [13].
bIsolated yield.
[Ɣ-Fe2O3@HAp-SO3H]
SO3H
O
H
N
O
R
N
O
O
+
+
-
OH
O3S
N
H
Ar
O
OH
N
product
N
H
I
O
N
-
VI
Ar
SO3H
RNH2
OH
Fe2O3
HAp
O
NR
Ar
SO3H
H
N
R
H
N
V
+
H
Ar
N
O
-
O
O3S
H
NH
H
NHR
Ar
RHN
H
O
O
O
II
SO3H
H N
2 ..
III
-CO2
-H2O
IV
Scheme (2). Proposed mechanism.
2.1. Microbial Test
apparatus. The NMR spectra were measured on an Ul-
1
trashield 400 Bruker (400 MHz for H and 100 MHz for
All products were screened for their in vitro antibacterial
activity against two Gram-negative bacterial strains: Es-
cherichia coli (E. coli) and Pseudomonas aeruginosa (P.
aeruginosa) and two Gram-positive bacterial strains: Staphy-
lococcus aureus (S. aureus) and Micrococcus luteus (M. lu-
teus) by paper diffusion method. Moderate to significant
antibacterial activities were for the prepared quinazolinones
(Table 5). Tetracyclin and ciprofloxacin were used as refer-
ence drugs (ref). All the synthesized products, in the concen-
tration of 20 µg/ml, were tested [2, 17, 18, 21].
13C) spectrometer using TMS as an internal standard and
DMSO-d6 as the solvent. Sonication was performed using a
Sono Swiss ultrasonic with a frequency of 50 or 60 Hz and a
nominal power 280 W. FT-IR spectra were determined on an
Alpha Bruker spectrophotometer using the pressed KBr [8,
19].
3.2. Synthesis of [Ɣ-Fe2O3@HAp], [Ɣ-Fe2O3@HAp-
SO3H]
FeCl2.4H2O (1.85 mmol) and FeCl3.6H2O (3.7 mmol)
were dissolved in (30 ml) water and then were added to
(10 ml) NH4OH solution (25%), until a black precipitate of
Fe3O4 was obtained. After 15 min, the milky solution was
obtained by adding 100 ml of Ca(NO3)2.4H2O (33.7 mmol,
0.05 M) and (NH4)2HPO4 (20 mmol, 3.0 M) solutions were
3. EXPERIMENTAL
3.1. Apparatus, Materials
All the materials were purchased from Merck and Ald-
rich. The melting points were recorded on a Thermo 9100

Ultrasonic Assisted Synthesis of 2, 3-Dihydroquinazolin-4(1H)-ones
Letters in Organic Chemistry, 2020, Vol. 17, No. 1 27
Table 3. The one-pot reactiona of isatoic anhydride, pyrazole carbaldehydes and ammonium salts or primary amines in diverse
conditions.
Aldehyde
(R2)
Time
(min)
Yield
(%)c
Entry
Amine
Product
Conditions
Catalystb
M.p. (°C)
[Ɣ-Fe2O3@HAp-SO3H]
1
60°C/ultrasound
4-OMe
2-OH
4-OH
4-Cl
NH4OAc
NH4OAc
NH4OAc
NH4OAc
NH4OAc
a
b
c
d
e
60
60
50
70
45
92
89
93
85
93
223-225
236-238
235-237
190-192
238-240
[4]
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
2
[4]
60°C/ultrasound
60°C/ultrasound
60°C/ultrasound
60°C/ultrasound
3
[4]
4
[4]
5
[4]
H
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
None
6
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
(NH4)2CO3
C6H5NH2
f
g
h
i
60°C/ultrasound
60°C/ultrasound
60°C/ultrasound
60°C/ultrasound
60°C/ultrasound
Reflux/Stirring
Reflux/Stirring
Reflux/Stirring
Reflux/Stirring
Reflux/Stirring
Reflux/Stirring
Reflux/Stirring
Reflux/Stirring
Reflux/Stirring
Reflux/Stirring
45
55
92
91
93
94
88
70
70
72
74
65
75
73
70
78
66
284-286
193-195
205-207
219-221
215-217
285-287
192-194
204-206
218-220
216-218
285-287
194-196
204-206
220-222
216-218
7
8
4-MeC6H4NH2
4-OEtC6H4NH2
4-ClC6H4NH2
(NH4)2CO3
60
9
55
10
11
12
13
14
15
16
17
18
19
20
j
80
f
360
370
370
365
390
180
190
200
190
210
C6H5NH2
g
h
i
None
4-MeC6H4NH2
4-OEtC6H4NH2
4-ClC6H4NH2
(NH4)2CO3
None
None
j
None
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
[Ɣ-Fe2O3@HAp-SO3H]
f
C6H5NH2
g
h
i
4-MeC6H4NH2
4-OEtC6H4NH2
4-ClC6H4NH2
j
aReaction conditions: isatoic anhydride (1 mmol), pyrazole carbaldehydes (1 mmol) (Table 4) and ammonium salts (ammonium acetate: 1.2 mmol, ammonium carbonate: 0.6 mmol)
or primary amines (1.2 mmol) in H2O: EtOH (3:1).
bAmount of catalyst used for reactions: 10 mg.
cIsolated yield.
Table 4. Physical data for the derivatives of pyrazole-4-carbaldehydes.
Entry
R2
Molecular Formula
Molecular Weight
M.p. (°C)
Yield (%)
1
2
3
4
5
4-OMe
2-OH
4-OH
4-Cl
C17H14O2
C16H12O2
C16H12O2
C16H11ClO
C16H12O
278
264
123-125
115-117
233-235
148-150
156-158
90
80
83
88
93
264
282.5
248
H
adjusted to pH=11, added drop-wise to the black precipitate
over 30 min, and then heated to 90°C for 2h. The solutions
were cooled down and aged overnight at room temperature.
Following this, the dark brown precipitate was obtained,
filtered, washed with water and air-dried under vacuum. The
reddish-brown powder of [Ɣ-Fe2O3@HAp] was formed by
heating to 300°C for 3h.
1g ClSO3H was added to 1g [Ɣ-Fe2O3@HAp]. The mix-
ture was stirred until the HCl gas evolution stopped for 6h.
Then the nanocatalyst was separated by an external magnet,
washed with water and with (100 ml) diethyl ether twice
and dried under vacuum at room temperature (Scheme 3)
[5, 13].

28 Letters in Organic Chemistry, 2020, Vol. 17, No. 1
Sina et al.
Table 5. Antibacterial activity of the derivatives of 2, 3-dihydroquinazolin-4(1H)-one.
Zone of Growth Inhibition in (mm)
Compounds
S. aureus
P. aeruginosa
E. coli
M. luteus
a
7
8
16
20
10
10
24
18
11
13
17
12
-
18
14
16
12
15
12
15
7
25
7
b
c
21
13
25
20
6
12
14
13
22
20
16
8
d
e
f
g
h
15
-
i
j
10
7
5
10
-
DMSO
-
-
Tetracyclin (ref)
Ciprofloxacin (ref)
16
20
20
22
18
20
20
18
HAp
HAp
Fe2O3
OSO3H
OSO3H
OSO3H
1. Ca2+, PO43-, NH4OH
2. Calcination
ClSO3H
Fe2O3
Fe (II) + Fe (III)
Scheme (3). Synthesis of [Ɣ-Fe2O3@HAp-SO3H].
3.3. General Procedure for the Synthesis of Pyrazole
Carbaldehydes
(ammonium acetate: 1.2 mmol, ammonium carbonate: 0.6
mmol), pyrazole carbaldehyde (1 mmol) and nanocatalyst
(10 mg) in H2O: EtOH (3:1) was poured into a 25 ml round-
bottomed flask and positioned in the ultrasonic and irradiated
at 60°C. The progress of the reaction was checked by TLC.
The solid catalyst was separated by an external magnet. The
precipitation of the reaction was filtered off, washed with
water and ethanol and recrystallized from ethanol to give
pure products (Scheme 1) (Table 3) [8, 12, 19].
A mixture of acetophenone (43 mmol), phenylhydrazine
(6 ml) and 30 ml water was stirred for 30 min. The resulted
mixture was filtered, washed with water to remove the ex-
cess chemicals and then dried. Then, 15 mmol of hydrazone
was dissolved in Vilsmeir-Hack reagent (DMF: POCl3) (25:5
ml), stirred at 50-60°C for 5-6 h, poured onto crushed ice
and neutralized with sodium bicarbonate. Following this, the
resulting solid was filtered, washed with water and dried to
obtain pyrazole carbaldehyde (Scheme 4) [20-22].
3.4.1. 2-(1, 3-diphenyl-1H-pyrazole-4-yl)-2, 3-dihydroquin-
azolin-4(1H)-one (f)
3.3.1. 1,3-Diphenyl-1H-pyrazole-4-carbaldehyde
Brown solid mp : 284-286°C. FT-IR (KBr): 3260 (N-H),
3061, 1663 (C=O), 1499-1550 (C=Carom), 1379 cm-1.
1HNMR (400 MHZ, DMSO-d6): δH = 8.92 (s, NHCO), 8.33
(NCH=, s, 1H), 7.98 (d, 1H, J=8.1 Hz), 7.81 (d, 1H, J=7.4
Hz), 7.68 (d, 1H, J=7.6 Hz), 7.55 (t, 1H, J=7.8 Hz), 7.49 (t,
1H, J=7.4 Hz), 7.36 ( t, 1H, J=7.3 Hz), 7.30 (t, 1H, J=7.5
Hz), 7.09 (s, NH), 6.78 (t, 1H, J=8.3 Hz) 5.91 (2NCH-, s,
1H). 13CNMR (100 MHZ, DMSO-d6): δC = 60.2 (2NCH-),
114.6, 117.7, 118.2, 118.6, 120.3, 126.5,127.1, 127.5, 128,
128.3, 128.4, 128.5, 129.4, 129.6, 129.7, 132.3, 133.2, 139.3,
148.6, 150.8, 164.1 (C=O); Anal. Calcd for C23H18N4O:
C,75.39; H, 4.95; N, 15.29%; Found: C, 75.48; H, 5.01; N,
15.21%.
Creamy solid mp: 156-158°C. FT-IR (KBr): 3060 (Ar-
CH), 2786-2837 (CH=O), 1672 (C=O), 1451-1525-1226
1
(-C=C), (-C=N), (-N-N) cm-1. HNMR (400 MHZ, DMSO-
d6): δH = 9.88 (s, 1H, -CH=O), 8.53 (s, 1H, -NCH=), 7.75-
7.37 (m, 10H, Ar-H). 13CNMR (100 MHZ, DMSO-d6): δC =
189.7 (CH=O), 154.3 (C=N pyrazole), 133.4 (CH-N pyra-
zole), 119.1 (C=C pyrazole), 145.6, 142.5, 130.9, 130.2,
128.7, 126.6, 122.4, 118.8, 116.9.
3.4. General Procedure for the Synthesis of Products (a-j)
The mixture of one-pot three component of isatoic
anhydride (1 mmol), amines (1.2 mmol) or ammonium salts

Ultrasonic Assisted Synthesis of 2, 3-Dihydroquinazolin-4(1H)-ones
Letters in Organic Chemistry, 2020, Vol. 17, No. 1 29
O
CH3
NH
CH3
N
PhNHNH2
CH3
N
NH
N
N
DMF
POCl3
CHO
Scheme (4). Synthesis of pyrazole carbaldehyde.
3.4.2. 2-(1, 3-diphenyl-1H-pyrazole-4-yl)-3-phenyl-2, 3-
dihydroquinazolin-4(1H)-one (g)
6.71 (d, 1H, J=8.3 Hz), 6.45 (2NCH-, s, 1H), 3.91 (q, 2H,
J=6.8 Hz), 1.26 (t, 3H, J=6.6 Hz). 13CNMR (100 MHZ,
DMSO-d6): δC = 14.5 (CH3), 63 (CH2), 66.5 (2NCH-), 113.9,
114.1, 114.2, 114.7, 114.8, 115.4, 117.9, 118.2, 118.3, 120.3,
122.1, 126.5, 128.1, 128.1, 128.2, 128.3, 128.4, 128.8, 129.5,
129.7, 132.3, 132.3, 133.5, 139, 147, 150.6, 156.8, 163
(C=O); Anal. Calcd for C31H26N4O2: C, 76.52; H, 5.39; N,
11.51%; Found: C, 76.60; H, 5.45; N, 11.46%.
Brown solid mp : 193-195°C. FT-IR (KBr): 3266 (N-H),
3063, 1625 (C=O), 1494-1545 (C=Carom), 1397 cm-1.
1HNMR (400 MHZ, DMSO-d6): δH = 8.72 (NCH=, s, 1H),
7.89 (m, 1H), 7.74 (d, 1H, J=7.6 Hz), 7.52 (d, 1H, J=7.3 Hz),
7.29 (t, 1H, J=7.7 Hz), 7.28 (d, 1H, J=7.6 Hz), 7.23 (d, 1H,
J=7.0 Hz), 7.17 (d, 1H, J=8.0 Hz), 6.92 (t, 1H, J=7.9 Hz),
6.90 (NH, s, 1H), 6.61 (2NCH-, s, 1H). 13CNMR (100 MHZ,
DMSO-d6): δC = 66.3 (2NCH-), 114.9, 115.5, 118.3, 118.3,
118.4, 120.1, 126.6, 126.9, 127.9, 128.1, 128.2, 128.3, 128.4,
128.5, 128.6, 128.6, 128.7, 129, 129.6, 129.7, 132.3, 133.6,
139, 139.9, 147, 147.1, 150.6, 162.9 (C=O); Anal. Calcd for
C29H22N4O: C, 78.71; H, 5.01; N, 12.66%; Found: C, 78.76;
H, 5.10; N, 12.74%.
3.4.5. 3-(4-chlorophenyl)-2-(1, 3-diphenyl-1H-pyrazole-4-
yl)-2, 3-dihydroquinazolin-4(1H)-one (j)
Brown solid mp : 215-217°C. FT-IR (KBr): 3275 (N-H),
3120, 1631 (C=O), 1493-1551 (C=Carom), 1380 cm-1.
1HNMR (400 MHZ, DMSO-d6): δH = 8.22 (NCH=, s,1H),
7.92 (d, 1H, J=8.1 Hz), 7.77 (d, 1H, J=7.4 Hz), 7.70 (d, 1H,
J=7.6 Hz), 7.63 (t, 1H, J=7.8 Hz), 7.52 (t, 1H, J=7.4 Hz),
7.45 (m, 1H), 7.05 (NH, s, 1H), 6.01 (2NCH-, s, 1H).
13CNMR (100 MHZ, DMSO-d6): δC = 66.2 (2NCH-), 114.9,
115, 115.2, 118, 118.3, 119.2, 119.8, 126.6, 127.7, 128.2,
128.2, 128.3, 128.4, 128.6, 128.7, 129.2, 129.3, 129.6, 129.7,
129.8, 130.9, 132.3, 133.8, 138.6, 139, 147.2, 150.6, 163
(C=O); Anal. Calcd for C29H21ClN4O: C, 73.03; H, 4.44; N,
11.75%; Found: C, 73.11; H, 4.50; N, 11.69%.
3.4.3. 2-(1, 3-diphenyl-1H-pyrazole-4-yl)-3-(p-tolyl)-2, 3-
dihydroquinazolin-4(1H)-one (h)
Brown solid mp : 205-207°C. FT-IR (KBr): 3277 (N-H),
3120, 1634 (C=O), 1503-1551 (C=Carom), 1381 cm-1.
1HNMR (400 MHZ, DMSO-d6): δH = 8.62 (NCH=, s, 1H),
7.82 (d, 1H, J=7.8 Hz), 7.77 (d, 1H, J=7.6 Hz), 7.65 (d, 1H,
J=6.7 Hz), 7.49 (t, 1H, J=7.6 Hz), 7.42 (d, 1H, J=7.3 Hz),
7.41 (t, 1H), 7.38 (NH, s, 1H), 7.33 (d, 1H, J=8.2 Hz), 6.97
(t, 1H, J=8.0 Hz), 6.81 (t, 1H, J=7.9 Hz), 6.48 (2NCH-, s,
1H), 2.19 (s, 3H). 13CNMR (100 MHZ, DMSO-d6): δC = 20.5
(CH3), 66.3 (2NCH-), 114.9, 114.9, 115.5, 117.9, 118.2,
120.3, 120.3, 120.5, 127.7, 128.1, 128.2, 128.2,128.3, 128.5,
128.9, 128.9, 129, 129.6, 129.7, 132.3, 133.6, 135.8, 137.3,
139, 147, 150.6, 162.9 (C=O); Anal. Calcd for C30H24N4O:
C, 78.92; H, 5.30; N, 12.27%; Found: C, 78.84; H, 5.35; N,
12.33%.
CONCLUSION
In summary, we have successfully developed a conven-
ient and facile synthetic protocol to produce 2, 3-
dihydroquinazolin-4(1H)-ones via the selectivity reactions
involving isatoic anhydride, pyrazole carbaldehydes and
amines or ammonium salts using [Ɣ-Fe2O3@HAp-SO3H] as
a reusable catalyst under sonication. The synthesized prod-
ucts have shown moderate to significant antibacterial activi-
ties against the examined microbial strains.
3.4.4. 2-(1, 3- diphenyl-1H-pyrazole-4-yl)-3-(4-ethoxy-
phenyl)-2, 3-dihydroquinazolin-4(1H)-one (i)
CONSENT FOR PUBLICATION
Brown solid mp : 219-221°C. FT-IR (KBr): 3303 (N-H),
3060, 2978, 1632 (C=O), 1508-1551 (C=Carom), 1388 cm-1.
1HNMR (400 MHZ, DMSO-d6): δH = 8.61 (NCH=, s, 1H),
7.81 (d, 1H, J=7.7 Hz), 7.77 (d, 1H, J=7.5 Hz), 7.64 (d, 1H,
J=6.5 Hz), 7.50 (t, 1H, J=7.4 Hz), 7.41 (d, 1H, J=7.0 Hz),
7.34 (m, 1H), 6.96 (d, 1H, J=8.1 Hz), 6.81 (t, 1H, J=8.3 Hz),
Not applicable.
FUNDING
We are grateful to the Research Council of the University
of Guilan for financial support.

30 Letters in Organic Chemistry, 2020, Vol. 17, No. 1
Sina et al.
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Yang, L.J.; Luo, J.G.; Wang, X.C. Heterocycles, 2017, 94, 1027-
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CONFLICT OF INTEREST
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Ghashang, M.; Azizi, K.; Moulavi Pordanjani, H. Chines. J. Chem.,
2011, 29, 1617-1623.
The authors confirm that this article content has no con-
flict of interest.
Sharmila Rani, C.; Suresh, N.; Basaveswara Rao, M.V.; Pal, M.
Arab. J. Chem., 2016, 26, 355-364.
ACKNOWLEDGEMENTS
Safari, J.; Gandomi Ravandi, S. J. Mol. Struct., 2014, 1072, 173-
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Declared none.
Mamani, L.; Sheykhan, M.; Heydari, A.; Faraji, M.; Yamini, Y.
Appl. Catal. A Gen., 2010, 377, 64-69.
Zhang, Z.H.; Lu, H.Y.; Yang, S.H.; Gao, J.W. J. Comb. Chem.,
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