Synthesis of pyrazol-quinazolinones and 2,3-dihydroquinazolin-4(1H)-ones using CoAl2O4 nanoparticles as heterogeneous catalyst

Article abstract of DOI:10.1007/s13738-019-01729-9

Abstract: The preparation and characterization of cobalt aluminate (CoAl₂O₄) magnetic nanoparticles and its application as a catalyst for the synthesis of a novel class of pyrazol-quinazolinones and 2,3-dihydroquinazolin-4(1H)-ones is described. The structure of the catalyst was studied by Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, and vibrating sample magnetometer analysis. The resulting cobalt aluminate (CoAl₂O₄) was an efficient catalyst and affords the desired products in good to excellent yields. Moreover, the catalyst could be easily recovered by magnetic separation and recycled for four times without significant loss of its catalytic activity. Graphic abstract: 2,3-Dihydroquinazolin-4(1H)-ones and a novel class of pyrazol-quinazolinones were synthesized through one-pot condensation reaction of isatoic anhydride, aromatic aldehydes, and amines using CoAl₂O₄ as nanoparticle heterogeneous catalyst in refluxing ethanol.[Figure not available: see fulltext.].

Full text of DOI:10.1007/s13738-019-01729-9

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-019-01729-9
ORIGINAL PAPER
Synthesis of pyrazol‑quinazolinones
and 2,3‑dihydroquinazolin‑4(1H)‑ones using CoAl2O4 nanoparticles
as heterogeneous catalyst
Fatemeh Ahmadian1 · Alireza Barmak1 · Esmali Ghaderi2 · Masoumeh Bavadi1 · Hossein Raanaei3 ·
Khodabakhsh Niknam1
Received: 12 January 2019 / Accepted: 28 June 2019
© Iranian Chemical Society 2019
Abstract
The preparation and characterization of cobalt aluminate (CoAl2O4) magnetic nanoparticles and its application as a catalyst
for the synthesis of a novel class of pyrazol-quinazolinones and 2,3-dihydroquinazolin-4(1H)-ones is described. The structure
of the catalyst was studied by Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray difraction,
and vibrating sample magnetometer analysis. The resulting cobalt aluminate (CoAl2O4) was an efcient catalyst and afords
the desired products in good to excellent yields. Moreover, the catalyst could be easily recovered by magnetic separation
and recycled for four times without signifcant loss of its catalytic activity.
Graphic abstract
2,3-Dihydroquinazolin-4(1H)-ones and a novel class of pyrazol-quinazolinones were synthesized through one-pot conden-
sation reaction of isatoic anhydride, aromatic aldehydes, and amines using CoAl2O4 as nanoparticle heterogeneous catalyst
in refuxing ethanol.
Keywords CoAl2O4 nanoparticles · Pyrazol-quinazolinones · Heterogeneous catalyst · Isatoic anhydride ·
2,3-Dihydroquinazolinones
Introduction
Electronic supplementary material The online version of this
Catalytic process is the key of many chemical industries.
Within this subject, design of novel, highly active, and reus-
able catalysts has become a major area of research. Hetero-
geneous catalysts are favored, because of easy separation,
recycling, and the use of small amount in the production
article (https://doi.org/10.1007/s13738-019-01729-9) contains
supplementary material, which is available to authorized users.
* Khodabakhsh Niknam
niknam@pgu.ac.ir
Extended author information available on the last page of the article
Vol.:(0123456789)
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Journal of the Iranian Chemical Society
Scheme 1 Synthesis of
pyrazol-quinazolinone and
2,3-dihydroquinazolin-4(1H)-
one derivatives
[1–8]. As a matter of fact, the search for new efcient and
recyclable heterogeneous catalysts has received more atten-
tion. Among them, nanoparticles (NPs) have been more
desirable due to their remarkable advantages such as small
size, large specifc surface area, high dispersion property,
good catalytic activity and selectivity, and easily modifable
surface by chemical methods [9]. In this sense, magnetic
nanoparticles (MNPs) are arguably the most extensively
investigated and emerged as appealing catalyst supports
[8–17]. Their magnetic character makes them efective and
easily separable from the reaction system by applying an
external magnetic feld, which eliminates the necessity of
tedious fltration, centrifugation, or membrane separation
steps.
Recently, cobalt aluminate spinels (CoAl2O4) were pre-
pared and have attracted much attention due to their opti-
cal, catalytic, pigments, electrical and magnetic properties
[18–28]. Also, the other applications in ceramics, color
tubes, plastics, paint, rubber, and glass were reported [29,
30].
Fig. 1 FT-IR spectra of CoAl2O4 nanoparticles
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Journal of the Iranian Chemical Society
Fig. 2 XRD of nano-CoAl2O4. Left side is fresh, and right side is after recovery
2,3-Dihydroquinazolinone derivatives are important
compounds for pharmaceutical chemistry. They have shown
some pharmaceutical activities such as antifertility, antibac-
terial, antitumor, antifungal, and monoamine oxidase inhi-
bition [31–34]. In recent years, the synthesis of 2,3-dihy-
droquinazolinones was reported via a three-component
condensation reaction between isatoic anhydride, and
aldehydes with ammonium acetate or primary amine in
the presence of diferent reagents or catalysts. Some of
these reagents or catalysts are alum (KAl(SO4)2·12H2O)
[35], p-toluenesulfonic acid [36], amberlyst-15 microwave-
assisted [37], montmorillonite K-10 [38], ionic liquid [39],
Fig. 3 Adsorbtion–desorption of CoAl2O4 nanoparticles
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Journal of the Iranian Chemical Society
nanotubes [55], TiO2 nanoparticles [56], glycerosulfonic
acid [57], and carbon-SO3H [58].
The synthesis of new and important types of heterocyclic
compounds in green and eco-friendly conditions continues
to attract wide attention among synthetic chemists. Herein,
we describe a facile three-component condensation reac-
tion consisting of isatoic anhydride, aromatic aldehyde, and
amine in refuxing ethanol to synthesize the 2,3-dihydro-
quinazolin-4(1H)-ones and also a novel class of pyrazol-
quinazolinones derivatives (Scheme 1).
Experimental
Chemicals and reagents
Chemicals were purchased from Merck and Aldrich Chemical
Companies. The products were characterized by comparison of
their spectral and physical data with those reported in the litera-
ture. For recording 1H NMR spectra we use Bruker (500, 400,
or 300 MHz) Avance Ultrashield in pure deuterated DMSO-d6
and CDCl3 solvents with tetramethylsilane (TMS) as internal
standard. Mass spectra were recorded on a FINNIGAN-MAT
8430 mass spectrometer operating at 70 eV. FT-IR spectros-
copy (Shimadzu FT-IR 8300 spectrophotometer) was employed
for characterization of the products. Melting points determined
in open capillary tubes in a Barnstead Electrothermal 9100 BZ
circulating oil melting point apparatus. The reaction monitor-
ing was accomplished by TLC on silica gel PolyGram SILG/
UV254 plates. Column chromatography was carried out on
columns of silica gel 60 (70–230 mesh).
Fig. 4 Transmission electron microscopic (TEM) image of CoAl2O4
nanoparticles
silica sulfuric acid [40], Ga(OTf)3 [41], Zn(PFO)2 [42],
MCM-41-SO3H [43], Al(H2PO4)3 [44], Al/Al2O3 [45],
Fe3O4 nanoparticles [46], SiO2-FeCl3 [47], silica-bonded
S-sulfonic acid [48], silica-bonded N-propylsulfamic acid
[49], ethylenediamine diacetate [50], deep eutectic solvent
[51], SiO2-ZnCl2 [52], nano-copper [53], Cu-CNTs nano-
composite [54], metal complexes with multi-walled carbon
Fig. 5 SEM image of CoAl2O4 nanoparticles. Left side is fresh, and right side is after recovery
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Journal of the Iranian Chemical Society
Fig. 6 EDX of CoAl2O4 nanoparticles. Left side is fresh, and right side is after recovery
Fig. 7 TGA of CoAl2O4 nano-
particles
nitrate solution was then added slowly and kept at a tem-
Procedure for preparation of CoAl2O4 catalyst
perature close to 0 ºC in a bath room. Then, aqueous solution
of potassium hydroxide (5 eq) was added dropwise under
vigorous stirring. Meanwhile, a transparent green color to
dark blue colloidal solution was produced. The resulting col-
loidal solution was fltered and calcined at 700 °C for 2 h and
then kept in an autoclave for 24 h.
Stoichiometric amounts of cobalt nitrate hexahydrate (1 eq,
1.45 g) and aluminum nitrate nonahydrate (1 eq, 3.75 g)
were separately dissolved in deionized water (5 mL). Then,
polyethylene glycol 4000 (0.2 g) was added to the cobalt
nitrate solution under vigorous stirring. The aluminum
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Journal of the Iranian Chemical Society
9.0
7.5
12
10
8
a
b
6.0
4.5
6
3.0
4
1.5
2
0.0
0
-1.5
-3.0
-4.5
-6.0
-7.5
-9.0
-2
-4
-6
-8
-10
-12
-10000 -8000 -6000 -4000 -2000
0
2000 4000 6000 8000 10000
-10000 -8000 -6000 -4000 -2000
0
2000 4000 6000 8000 10000
Fig. 8 Vibrating sample magnetometer curve of synthesized CoAl2O4 nanoparticles. a Fresh CoAl2O4 and b after recovery
Table 1 Reaction of isatoic
anhydride and benzaldehyde
with aniline in the presence of
diferent amounts of catalysts
Entry
Catalyst (g)
Solvent
Conditions
Time (min)
Yield (%)a
1
2
3
4
5
6
7
8
–
Ethanol
Ethanol
Ethanol
Ethanol
Dichloromethane
Acetonitrile
Methanol
Toluene
Tetrahydrofuran
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Refux
Refux
Refux
Refux
Refux
Refux
Refux
80 °C
Refux
R.T.
50 °C
65 °C
Refux
Refux
Refux
600
120
120
120
120
120
120
120
120
480
120
120
240
240
240
–
45
89
89
20
70
85
<20
<20
Trace
30
50
50
CoAl2O4 (0.01)
CoAl2O4 (0.02)
CoAl2O4 (0.03)
CoAl2O4 (0.02)
CoAl2O4 (0.02)
CoAl2O4 (0.02)
CoAl2O4 (0.02)
CoAl2O4 (0.02)
CoAl2O4 (0.02)
CoAl2O4 (0.02)
CoAl2O4 (0.02)
Co(NO3)2·6H2O (0.02)
CoCl2·6H2O (0.02)
Acidic Al2O3 (0.02)
9
10
11
12
13
14
15
55
60
Ethanol
The molar ratio of isatoic anhydride:benzaldehyde:aniline was 1:1:1 mmol, respectively, in solvent (5 mL)
at refux conditions
bIsolated yield
chromatography on silica gel. The recovered catalyst was
reused for subsequent runs.
General procedure for the synthesis
of pyrazol‑quinazolinones (4)
To a mixture of isatoic anhydride (1 mmol), 5-chloro-3-me-
thyl-1-phenyl-1H-pyrazole-4-carbaldehyde (3) (1 mmol),
and aniline derivatives (1 mmol) in 5 mL ethanol was added
0.02 g nano-CoAl2O4, and the resulting mixture was heated
under refux conditions. After completion of the reaction,
as indicated by TLC, the nano-CoAl2O4 was removed by an
external magnet while the mixture was hot and the remain-
ing was washed with warm ethanol (2×3 mL). The mixture
was cooled to precipitate the corresponding pyrazol-quina-
zolinone products which were fnally purifed by column
2‑(5‑chloro‑3‑methyl‑1‑phenyl‑1H‑pyra‑
zol‑4‑yl)‑3‑phenyl‑2,3‑dihydroquinazolin‑4(1H)‑one
(4a)
m.p. 216-218 °C. IR (KBr): 1684 (N–C=O) cm−1. 1H NMR
(500 MHz, DMSO-d6) δ (ppm): 2.23 (s,1H), 6.47 (s, 1H),
6.75–6.81 (m, 2H), 7.19–7.22 (m, 3H), 7.28–7.35 (m, 6H),
7.45 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H), 7.72 (d,
J=7.8 Hz, 1H); 13C NMR (125 MHz, DMSO-d6) δ (ppm):
13.8, 66.6, 114.8, 115.2, 115.6, 118.1, 125.2, 126.8, 127.5,
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Journal of the Iranian Chemical Society
Scheme 2 Synthesis of pyrazol-
quinazolinone derivatives
128.3, 128.5, 128.9, 129.0, 129.8, 134.2, 137.8, 140.3,
148.4, 149.0, 163.9. Anal. Calcd. for C24H19ClN4O; C,
69.48; H, 4.62; Cl, 8.54; N, 13.50%. Found C, 69.17; H,
4.73; N, 13.21%. MS (m/z): 414 (M+), 323 (base peak).
J=7.4 Hz, 1H), 7.08–7.14 (m, 4H), 7.30–7.50 (m, 7H), 8.05
(d, J=7.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ (ppm):
13.9, 21.1, 67.0, 114.4, 114.7, 116.6, 119.7, 124.9, 127.1,
128.5, 129.1, 129.3, 129.5, 129.6, 133.8, 136.7, 137.2,
137.7, 146.7, 149.0, 164.3. Anal. Calcd. for C25H21ClN4O;
C, 70.01; H, 4.94; Cl, 8.26; N, 13.06%. Found C, 69.68; H,
4.90; N, 12.72%. MS (m/z): 428 (M+), 429 (M++1, base
peak).
2‑(5‑chloro‑3‑methyl‑1‑phenyl‑1H‑pyra‑
zol‑4‑yl)‑3‑(4‑chlorophenyl)‑2,3‑dihydroquinazo‑
lin‑4(1H)‑one (4b)
m.p. 219–221 °C. IR (KBr): 3270 (N–H), 1613 (N–C=O)
cm−1. 1H NMR (300 MHz, CDCl3) δ (ppm): 2.38 (s, 3H),
6.43 (s, 1H), 6.76 (d, J = 8.1 Hz, 1H), 6.98 (t, J = 7.5 Hz,
1H), 7.12–7.16 (m, 1H), 7.22–7.29 (m, 4H), 7.36–7.52
(m, 6H), 8.05 (dd, J1 =7.0 Hz, J2 =1.2 Hz, 1H),; 13C NMR
(125 MHz, DMSO-d6) δ (ppm): 13.3, 66.1, 114.4, 114.7,
115.1, 117.7, 124.7, 126.4, 127.0, 127.8, 128.1, 128.4,
128.5, 129.3, 133.8, 137.3, 139.8, 147.9, 148.5, 163.4. Anal.
Calcd. for C24H18Cl2N4O; C, 64.15; H, 4.04; Cl, 15.78 N,
12.47%. Found C, 63.79; H, 4.13; N, 12.11%. MS (m/z): 449
(M+, base peak), 450 (M++1), 451 (M+ +2).
2‑(5‑chloro‑3‑methyl‑1‑phenyl‑1H‑pyra‑
zol‑4‑yl)‑3‑(4‑hydroxyphenyl)‑2,3‑dihydroquinazo‑
lin‑4(1H)‑one (4d)
m.p. 236–238 °C. IR (KBr): 3300–3000 (OH & N–H),
1
1615 (N–C = O) cm−1. H NMR (300 MHz, DMSO-d6) δ
(ppm): 2.24 (s, 3H), 6.73 (s, 1H), 6.65–6.82 (m, 4H), 7.00
(d, J=8.4 Hz, 2H), 7.30–7.37 (m, 4H), 7.44–7.56 (m, 3H),
7.74 (d, J=6.9 Hz, 1H), 9.50 (brs, 1H); 13C NMR (75 MHz,
DMSO-d6) δ (ppm): 13.8, 66.8, 114.7, 115.2, 115.5, 115.8,
117.9, 125.1, 126.8, 128.5, 128.9, 129.3, 129.8, 131.4,
134.0, 137.8, 148.4, 149.0, 156.6, 164.0. Anal. Calcd. for
C24H19ClN4O2; C, 66.90; H, 4.44; Cl, 8.23; N, 13.00%.
Found C, 66.56; H, 4.49; N, 12.74%. MS (m/z): 430 (M+),
431 (M++1, base peak).
2‑(5‑chloro‑3‑methyl‑1‑phenyl‑1H‑pyra‑
zol‑4‑yl)‑3‑(p‑tolyl)‑2,3‑dihydroquinazo‑
lin‑4(1H)‑one (4c)
m.p. 190–192 °C. IR (KBr): 3289 (N–H), 1630 (N–C =O)
cm−1. 1H NMR (300 MHz, CDCl3) δ (ppm): 2.32 (s, 3H),
2.39 (s, 3H), 6.40 (s, 1H), 6.73 (d, J=7.8 Hz, 1H), 6.92 (t,
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Journal of the Iranian Chemical Society
Table 2 Preparation of
2,3-dihydroquinazolinones
catalyzed by CoAl2O4 in
refuxing ethanol
Entry R1
R2
Product Time (min) Yield (%)a M. P. °C M. P. °C (Lit.)
1
2
3
4
5
6
7
8
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–
6a
6b
6c
6d
6e
6f
120
130
130
130
150
130
200
130
80
89
83
80
82
80
82
78
92
80
90
92
87
89
75
70
88
87
82
85
80
75
75
–
207–209 205–206 [46]
235–237 235–237 [55]
221–223 223–225 [46]
216–218 219–220 [41]
205–207 204–205 [42]
223–225 215–216 [46]
197–199 197–200 [48]
198–200 197–198 [46]
243–247 244–246 [55]
246–248 241–243 [54]
225–227 227–228 [50]
151–153 151–154 [48]
156–158 156–158 [48]
249–251 248–250 [55]
235–237 235–236 [55]
227–228 223–225 [53]
179–180 178–180 [35]
203–205 198–200 [35]
201–203 195–197 [45]
195–197 194–196 [57]
216–218 216–219 [48]
250–252 252–254 [43]
4-F–C6H4–
4-Br–C6H4–
4-Cl–C6H4–
4-MeO–C6H4– C6H5–
4-Me–C6H4–
2-Thionyl-
C6H5-
4-Me–C6H4–
4-MeO–C6H4– 4-Me–C6H4–
4-MeO–C6H4– 4-MeO–C6H4–
4-Me–C6H4–
4-Cl–C6H4–
4-Me–C6H4–
4-Cl–C6H4–
4-Me–C6H4–
4-MeO–C6H4–
4-Cl–C6H4–
4-Br–C6H4–
4-F–C6H4–
C6H5–
C6H5–
4-Me–C6H4–
4-Me–C6H4–
6 g
6 h
6i
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
6j
130
130
90
6 k
6 l
6 m
6n
C6H5–CH2CH2–
C6H5–CH2CH2–
4-HO–C6H4–
90
200
120
120
100
130
120
120
160
130
360
2-HO–5–ClC6H3– 6o
H
H
H
H
H
H
H
6p
6q
6r
6 s
6t
6u
6v
–
2-Thionyl–
2-HO–C6H4-
Me–CH2CH2– C6H5-
–
–
aIsolated yield
General procedure for the synthesis of 2,3‑dihy‑
dro‑dihydroquinazolinone derivatives (6)
Results and discussion
Initially, cobalt aluminate with a spinel-type structure was
synthesized using a colloidal method, with slight diferences
from the method reported by Blanco et al. [26], and Ragu-
pathi and co-workers [27]. The preparation of CoAl2O4 was
carried out by adding the polyethylene glycol 4000 (0.2 g)
to the aqueous solutions of cobalt nitrate hexahydrate and
aluminum nitrate nonahydrate with stirring. Then, the potas-
sium hydroxide solution was added at temperature close to
0 °C. The resulting dark blue colloidal solution was fltered
and calcined at 700 °C for 2 h. Then, it was kept in an auto-
clave for 24 h (see supplementary information Figure S1).
The FT-IR spectrum of cobalt aluminate is shown in
Fig. 1. The absorption band at 480–590 cm−1 indicates the
presence of Co–O stretching frequencies, and the band at
640–760 cm−1 range belongs to Al–O vibrations. Also,
To a mixture of isatoic anhydride (1 mmol), aromatic alde-
hyde (1 mmol), and ammonium acetate or primary amine
(1 mmol) in 5 mL ethanol was added 0.02 g nano-CoAl2O4,
and the resulting mixture was heated under refux condi-
tions. After completion of the reaction, as indicated by TLC,
the nano-CoAl2O4 was removed by an external magnet.
The mixture was cooled to precipitate the corresponding
2,3-dihydroquinazolinone products which were fnally puri-
fed by recrystallization using hot ethanol. The recovered
catalyst was reused for subsequent runs.
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Journal of the Iranian Chemical Society
64.4% present for CoO and 29.3% present for Al2O3 (see
supplementary information). The increased active site of
CoAl2O4 nanoparticles was studied by the nitrogen adsorp-
tion–desorption isotherms from the BET analysis (Fig. 3).
The specifc surface area and pore volume of cobalt alu-
minate spinel catalyst were obtained as 38.569 m2 g−1 and
0.177 cm3 g−1, respectively (see supporting information).
Figure 4 shows TEM images of nano-CoAl2O4. The par-
ticle sizes were in the range of 10–80 nm. The TEM images
and XRD revealed the nanosized particles.
The morphology of nano-CoAl2O4 was investigated
by SEM methods. The SEM images demonstrate that the
obtained cobalt aluminate has a uniform structure and aggre-
gate sheets are detected (Fig. 5).
The EDX pattern of CoAl2O4 is shown in Fig. 6. This
analysis indicated the presence of constituent elements Al,
O, and Co in the cobalt aluminate.
TGA curve for the catalyst (CoAl2O4) is shown in Fig. 7.
The decrease in gravity began at about 170 °C, which indi-
cated the decomposition of the catalyst. The mass changes
were scanned for the ranges between −5 and +5 mg which
it has shown 2.89 mg and approximately 28.9% weight loss
mass.
Fig. 9 Separation of the catalyst with external magnet
The magnetization curve for CoAl2O4 nanoparticles was
run. It is of great importance that a catalyst should possess
sufcient magnetic and super-paramagnetic properties for
its practical application (Fig. 8).
The catalytic activity of CoAl2O4 nanoparticles was
investigated in the synthesis of 2,3-dihydroquinazolinones
via a one-pot three-component condensation reaction
between isatoic anhydride and aromatic aldehydes with
aniline derivatives. In a preliminary study, the reaction of
isatoic anhydride and benzaldehyde with aniline was chosen
as a model reaction in refuxing ethanol (Table 1). To illus-
trate the need of CoAl2O4 for this condensation we examined
the model reaction in the absence of CoAl2O4 in refuxing
ethanol (Table 1, entry 1). The results show clearly that
CoAl2O4 is an efective catalyst for this transformation and
in the absence of CoAl2O4 the reaction did not take place,
even after 10 h. As indicated in Table 1, the best results have
been obtained with 0.02 g of CoAl2O4 in refuxing ethanol.
By increasing the amount of CoAl2O4 to 0.03 g the yield of
corresponding product was not changed.
Fig. 10 Recyclability of nano-CoAl2O4 in the reaction of isatoic
anhydride and benzaldehyde with aniline. Reaction time=120 min
the Al–O–Co interactions have frequencies in the range of
450–800 cm−1 [25, 28].
The XRD. X-ray powder difraction for nano-CoAl2O4 is
shown in Fig. 2. The fgure indicates peaks at 31, 36, 55, 59,
65, and 77° 2θ that the spinel phase was obtained with high
crystallinity. However, small peaks at 44, 51, and 75° 2θ that
belong to CoO impurities were also detected, indicating the
precursor solution was slightly of-stoichiometry, which is in
agreement with the result previously reported by Granados
et al. [25]. The average crystal sizes, which were calculated
using Scherrer’s formula, were~26 and 28 nm for CoAl2O4
and CoO, respectively.
The model reaction was also examined in various sol-
vents in the presence of 0.02 g of CoAl2O4 (Table 1). As
shown in Table 1, condensation reaction in ethanol and
methanol gave the best results in the case of yield, and we
chose ethanol for environmental sustainability. Also, the
model reaction was converted into corresponding product
in ethanol at lower temperature in longer reaction times and
lower yields (Table 1, entries 10–12). In order to show the
efciency of the catalyst in comparison with its components
the model reaction was examined in the presence of cobalt
Also, the cobalt and aluminum contents in CoAl2O4 were
measured by XRF instrument. The XRF results showed
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Journal of the Iranian Chemical Society
Scheme 3 Plausible mechanism
for the synthesis of 2,3-dihydro-
quinazolin-4(1H)-ones
Table 3 Reaction of isatoic
anhydride and benzaldehyde
with aniline in the presence of
diferent amounts of catalysts
Catalyst
Catalyst load (g)
Time (min)
Yield (%)a
Refs.
p-Ts-OH
0.5 mol
0.3
0.11
2.5 h (3.5 h)
6.5 h (5 h)
6.5 h (3.5 h)
(50)
6 h
(15)
(15)
120 (120)
(10)
(90)
(150)
79 (60)
80 (73)
80 (90)
(86)
82
(90)
(92)
80 (85)
(87)
(87)
(86)
[35]
[37]
[39]
[40]
[41]
[43]
[45]
[46]
Montmorillonite K-10
Silica sulfuric acid
Ga(OTf)3
Zn(PFO)2
MCM-41-SO3H
Al/Al2O3
Fe3O4 nanoparticles
SiO2-FeCl3
SBSSA
0.05 mmol
0.027
0.005
0.036
0.15
0.005
0.005
0.1
[47]
[48]
[49]
SBNPSA
SiO2-ZnCl2
0.025
0.1 mmol
0.04
(14)
30
5
(89)
85
99
89 (88)
[51]
[52]
[53]
present work
Nano-copper
Cu-CNTs nanocomposite
CoAl2O4
0.005
120 (120)
aIsolated yield
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Journal of the Iranian Chemical Society
nitrate, cobalt chloride, and acidic alumina. The model
reaction was converted in the presence of cobalt nitrate and
cobalt chloride as catalysts into the corresponding product
after 240 min in 50% and 55% yields, respectively (Table 1,
entries 13 and 14). Also, acidic alumina converted the model
reaction after 240 min in 60% yield (Table 1, entry 15).
In order to synthesize the novel class of pyrazol-quina-
zolinones the reaction between 5-chloro-3-methyl-1-phe-
nyl-1H-pyrazole-4-carbaldehyde (3) and isatoic anhydride
with aniline derivatives was investigated under optimized
conditions. As shown in Scheme 2, the aniline derivatives
such as 3-chloro-aniline, 4-methyl-aniline, and 4-hydroxy-
aniline treated with isatoic anhydride and aldehyde 3 and
corresponding products 4a–d were obtained in good to high
yields.
C–O bond breaking in carbonyl group and forming of the
intermediate (1). Subsequently, a CO2 molecule left the
compound and intermediate (2) was attained. Then, the
catalytic-activated aldehyde group was attacked by an
ammonium nitrogen lone pair and intermediate (3) was
obtained. Finally, the product (6) was obtained by ring
formation and hydrogen displacement.
Finally, a comparative study of CoAl2O4 with other
recently reported catalysts for the synthesis of 2,3-diphe-
nyl-2,3-dihydroquinazolin-1H-4-one (6a) as a model
compound was made, which revealed that CoAl2O4 is an
equally efcient and reusable catalyst (Table 3).
Conclusions
The generality of this process was applied for the
synthesis of 2,3-dihydroquinazolinones via the reaction
between isatoic anhydride and the wide range of substi-
tuted and structurally diverse aromatic aldehydes with
anilines or ammonium salt under optimized conditions
(Table 2).
In conclusion, CoAl2O4 nanoparticles were prepared in the
presence of polyethylene glycol 4000 as a green and eco-
friendly medium. Introducing a novel class of pyrazol-quina-
zolinones and also, using magnetic heterogeneous catalyst
which easily removable by external magnet, easy and clean
work-up, high yields and recovery of the catalyst makes this
method practical for multi-component condensation reaction
of quinazolinone synthesis.
Aniline bearing electron-donating groups such as
methyl or methoxy, and electron-withdrawing groups such
as halogen substituted (F, Cl, and Br) was employed, and
all 2,3-dihydroquinazolinones were obtained in high to
excellent yields. Also, 2-phenylethyl amine as an aliphatic
amine gave corresponding product in high yield (Table 2,
entries 12 and 13). 2-Hydroxybenzaldehyde reacted with
isatoic anhydride and ammonium acetate gave correspond-
ing product after 130 min in 75% yield (Table 2, entry 22).
Heterocyclic aldehydes such as 2-thionyl were converted
into corresponding products in high yield (Table 2, entries
7 and 21). Moreover, the reaction between isatoic anhy-
dride and other aromatic aldehydes with ammonium ace-
tate gave corresponding products in high yields (Table 2).
Aliphatic aldehydes such as butanal failed to give the cor-
responding product under optimized reaction conditions
(Table 2, entry 23).
Acknowledgements We are thankful to Persian Gulf University
Research Council for partial support of this work.
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Afliations
Fatemeh Ahmadian1 · Alireza Barmak1 · Esmali Ghaderi2 · Masoumeh Bavadi1 · Hossein Raanaei3 ·
Khodabakhsh Niknam1
1
3
Department of Chemistry, Faculty of Sciences, Persian Gulf
University, Bushehr 75169, Iran
Department of Physics, Faculty of Sciences, Persian Gulf
University, Bushehr 75169, Iran
2
Faculty of Chemistry, Bu-Ali Sina University, PO
Box 6517838683, Hamedan, Iran
1 3