One-pot, three-component synthesis of 2,3-dihydroquinazolin-4(1H)-ones using p-Toluenesulfonic acid-paraformaldehyde copolymer as an efficient and reusable catalyst

Article abstract of DOI:10.1007/s00706-010-0376-3

p-Toluenesulfonic acid-paraformaldehyde copolymer (copolymer-PTSA) catalyzes the three-component, one-pot condensation reaction of isatoic anhydride, ammonium salts or aromaticand aliphatic amines, and aldehydes in refluxing ethanol. The catalyst is reusable and could be recycled for several runs without any decrease in its efficiency. Springer-Verlag 2010.

Full text of DOI:10.1007/s00706-010-0376-3

Monatsh Chem (2010) 141:1113–1115
DOI 10.1007/s00706-010-0376-3
ORIGINAL PAPER
One-pot, three-component synthesis of 2,3-dihydroquinazolin-
4(1H)-ones using p-toluenesulfonic acid–paraformaldehyde
copolymer as an efficient and reusable catalyst
Ali Saffar-Teluri Shiva Bolouk
•
Received: 19 July 2009 / Accepted: 5 August 2010 / Published online: 26 August 2010
Ó Springer-Verlag 2010
Abstract p-Toluenesulfonic acid–paraformaldehyde co-
polymer (copolymer-PTSA) catalyzes the three-component,
one-pot condensation reaction of isatoic anhydride, ammo-
nium salts or aromatic and aliphatic amines, and aldehydes in
refluxing ethanol. The catalyst is reusable and could be
recycled for several runs without any decrease in its
efficiency.
nitroarenes [12]. All these procedures have certain limita-
tions such as tedious processes, long reaction times, harsh
reaction conditions, and low yields.
There has been growing interest in the catalytic appli-
cation of functional polymers in organic synthesis. Several
polymers having acidic or basis properties like polyanilines
[13], polyvinyl pyridine [14], polyvinyl pyrrolidone [15],
and cation and anion exchange resins [16–18] have been
studied for use in a variety of chemical transformations.
These solid catalysts have high acidity and alkalinity and
often require a high degree of agitation, which causes
rupture of the polymeric matrix. Hence, the development of
a heterogeneous, active, and selective polymeric acid cat-
alyst seems to be a challenging task.
Keywords 2,3-Dihydroquinazolin-4(1H)-ones Á
Heterogeneous catalyst Á Copolymer-PTSA
Introduction
Quinazolinones are a class of N-heterocycles that has
attracted much attention because of their broad range of
pharmacological activities such as anticancer [1], anti-
inflammatory [2], antidiuretic [3], and anticonvulsant [4]
activities. 2,3-Dihydroquinazolin-4(1H)-ones in particular
have various biological activities, and are also key inter-
mediates for the synthesis of quinazolin-4(3H)-ones [5, 6].
Several methods have been reported for synthesis of qui-
nazolinone and aryl-substituted quinazolinone compounds
including cyclization of o-acylaminobenzamides [7], ami-
dation of 2-aminobenzonitrile followed by oxidative ring
closure [8], reduction of the azide functionality [9], prep-
aration from isatoic anhydrides and Schiff bases [10],
Lewis acid–surfactant combined catalysts under aqueous
micellar media [11], and Pd-catalyzed heterocyclization of
In connection with our previous work on the synthesis of
pharmaceutically important heterocyclic compounds [19],
herein we report the one-pot condensation of isatoic
anhydride, ammonium salts or aromatic and aliphatic
amines, and aldehydes in the presence of p-toluenesulfonic
acid–paraformaldehyde copolymer (copolymer-PTSA) in
refluxing ethanol.
Results and discussion
To optimize the reaction conditions, we conducted the
reaction of isatoic anhydride and benzaldehyde with
ammonium carbonate or aniline in various solvents such as
CH OH, CH CH OH, H O, CH CN, CH Cl , CHCl , and
3
3
2
2
3
2
2
3
CCl . The results showed that the highest product yield was
4
obtained in methanol and ethanol. However, because of the
toxicity of methanol, all reactions were carried out in
ethanol. Then the effect of amount of catalyst on the
conversion rate of the reaction was studied by varying the
amount of copolymer-PTSA under reflux (Table 1). It was
A. Saffar-Teluri (&) Á S. Bolouk
Department of Chemistry, Faculty of Material Science
and Engineering, Islamic Azad University-Najafabad Branch,
Najafabad, Iran
e-mail: a.saffar.t@iaun.ac.ir
123

1
114
A. Saffar-Teluri, S. Bolouk
Table 2 Copolymer-PTSA-catalyzed synthesis of monosubstituted
derivatives of 2,3-dihydroquinazolin-4(1H)-one
Table 1 Optimization of the catalyst amounts for the synthesis of
,3-dihydro-2-phenylquinazolin-4(1H)-one
2
1
Product
R
X
Time Yield
a
M.p.
(°C)
Ref.
Entry
Amount of
copolymer-PTSA (g)
Time
(h)
Yield
a,b
(%)
(h)
(%)
2
3
-
1
a
Ph
CO
5
87, 85, 86, 219–221 [24]
b
84, 83
1
2
3
4
5
6
a
0
24
15
9
15
58
64
87
86
88
2
2
2
2
-
-
-
-
0.1
0.2
0.3
0.4
0.5
1b
4-ClC
6
H
4
CO
CO
CO
CO
CO
CH
CH
3
3
3
3
3
3
3
6
94
81
89
82
83
77
82
70
78
71
80
79
71
72
75
74
77
198–200 [24]
166–168 [25]
178–180 [24]
234–236 [23]
209–211 [25]
219–221 [24]
198–200 [24]
166–168 [25]
178–180 [24]
234–236 [23]
209–211 [25]
219–221 [24]
198–200 [24]
166–168 [25]
178–180 [24]
234–236 [23]
209–211 [25]
1
1
1
1
1
c
d
e
f
2-CH
4-CH
4-CH
3
OC
6
H
H
4
4
5.5
6.5
6
3
3
OC
6
5
C
6
H
4
5
2-
3,4-(CH
Ph
3
O)
2
C
H
6 3
H
6 3
H
6 3
5.5
5
5
-
-
-
-
-
-
a
COO
COO
1b
1c
4-ClC
6
H
4
6.1
5.7
6.7
6.5
6
Reaction conditions: isatoic anhydride (1 mmol), ammonium car-
3
bonate (0.6 mmol), benzaldehyde (1 mmol), and ethanol (5 cm ),
2-CH OC H
3
3
3
6
4
4
3
CH COO
1
d
4-CH
4-CH
OC
6
H
CH
CH
CH
3
COO
3
COO
3
COO
reflux
b
1e
C
6
H
4
Isolated yields
1
1
f
3,4-(CH
Ph
3
O)
2
C
-
a
Cl
Cl
Cl
Cl
Cl
Cl
5
-
found that 0.3 g of copolymer-PTSA was sufficient to carry
out this reaction smoothly. An increase in the amount of
copolymer-PTSA to more than 0.3 g showed no substantial
improvement in the yield, whereas the yield was reduced by
decreasing the amount of copolymer-PTSA to 0.2 and 0.1 g.
The use of ammonium salts as ammonia source in syn-
thetic reactions has been well known for a long time [20–23].
In order 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 (Scheme 1).
In all cases, monosubstituted 2,3-dihydroquinazolin-4(1H)-
ones were produced in good yields. All of the products are
known compounds and were identified by comparison of
their physical and spectral data with those of authentic
samples [24–27]. The results are summarized in Table 2.
Disubstituted derivatives of 2,3-dihydroquinazolin-
1b
1c
4-ClC
6
H
4
6.2
5.3
7
-
-
-
-
2-CH
4-CH
4-CH
3
OC
6
H
H
4
4
1
1
1
d
e
f
3
3
OC
6
C
6
H
4
6.1
6.2
3 2
3,4-(CH O) C
a
Isolated yields
b
The catalyst was reused for five runs
In conclusion, we have successfully developed an effi-
cient heterogeneous catalyzed (copolymer-PTSA)
synthesis of quinazoline derivatives by the three-compo-
nent, one-pot condensation of commercially available
starting materials. The method offers several advantages
including high yield of products, recyclability of the cata-
lyst, and easy experimental work-up procedure.
4
(1H)-one were also afforded in good yields by treatment
Experimental
of isatoic anhydride and aryl aldehydes with primary aro-
matic and aliphatic amines in the presence of copolymer-
PTSA in refluxing ethanol (Scheme 2). The results are
presented in Table 3.
All materials were of commercial reagent grade. Isatoic
anhydride, aldehydes, ammonium salts, and primary
amines were obtained from Merck. FT-IR spectra were
-
1
The recyclability of the catalyst was investigated by using
a model reaction between isatoic anhydride and benzalde-
hyde with ammonium carbonate or aniline in the presence of
copolymer-PTSA. After completion of the reaction, the
catalyst was filtered. The recycled catalyst was used for
further runs and its activity did not show any significant
decrease even after five runs (Table 2, 1a; Table 3, 2i).
obtained in the range 400–4,000 cm
with a Nicolet
Impact 400D spectrometer using potassium bromide pel-
1
lets. H NMR spectra were measured with a Bruker DRX-
500 (500 MHz) using TMS (tetramethylsilane) as internal
standard. Melting points were measured on a Mettler FPS.
The catalyst (copolymer-PTSA) was synthesized by the
reported procedure [28] (Scheme 3).
Scheme 1
1
23

One-pot, three-component synthesis of 2,3-dihydroquinazolin-4(1H)-ones
1115
Scheme 2
residue was concentrated. The crude products were recrys-
tallized from ethanol.
Table 3 Copolymer-PTSA-catalyzed synthesis of disubstituted deriv-
atives of 2,3-dihydroquinazolin-4(1H)-one
2
3
R
Product
R
Time Yield
a
M.p.
(°C)
Ref.
Acknowledgments We gratefully acknowledge the financial sup-
port from the Research Council of Islamic Azad University,
Najafabad Branch.
(
h)
(%)
2
2
2
2
2
2
2
2
2
a
b
c
d
e
f
Me Ph
3.4
3.6
3.2
3.7
4
84
164–166 [10]
190–192 [10]
145–147 [10]
134–137 [10]
132–135 [10]
159–161 [10]
176–178 [10]
124–126 [10]
205–207 [26]
Me 4-ClC
6
H
4
82
Me 4-CH OC
3
6
H
4
85
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Et
Et
Et
Et
Et
Ph
83
4-ClC
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Scheme 3
General procedure for the synthesis of mono-
and disubstituted derivatives
of 2,3-dihydroquinazolin-4(1H)-one
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amine (1.2 mmol), and aldehyde (1 mmol) in 5 cm ethanol
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at reflux for the appropriate time (Table 2; Table 3). After
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123