A carbon material as a strong protonic acid for efficient synthesis of 4(3H)-quinazolinones

Article abstract of DOI:10.1002/cjoc.201180242

Carbon-based solid acid catalyst has been applied to catalyzing the synthesis of 4(3H)-quinazolinones from the cyclization reaction of 2-aminobenzamide with aroyl chlorides. The results showed that the catalyst was very efficient with the average yield over 85%. This carbon material with strong protonic acid sites as heterogeneous catalyst has some advantages such as high activity, strikingly simple work-up procedure, non-pollution, and reusability, which will contribute to the green process greatly.

Full text of DOI:10.1002/cjoc.201180242

FULL PAPER
A Carbon Material as a Strong Protonic Acid for Efficient
Synthesis of 4(3H)-Quinazolinones
Tavakoli-Hoseini, Niloofar*
Davoodnia, Abolghasem
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran
Carbon-based solid acid catalyst has been applied to catalyzing the synthesis of 4(3H)-quinazolinones from the
cyclization reaction of 2-aminobenzamide with aroyl chlorides. The results showed that the catalyst was very effi-
cient with the average yield over 85%. This carbon material with strong protonic acid sites as heterogeneous cata-
lyst has some advantages such as high activity, strikingly simple work-up procedure, non-pollution, and reusability,
which will contribute to the green process greatly.
Keywords carbon-based solid acid, heterogeneous catalysis, 2-aminobenzamide, aroyl chlorides, cyclization
1
6-18
Introduction
lysts such as sulfuric acid.
It is also insoluble in
common organic solvents, causes low corrosion, and
shows environmental acceptability. Furthermore, the
products could be easily separated from the reaction
mixture and the catalyst is recoverable without decreas-
ing its activity. To the best of our knowledge there are
no examples on the use of carbon-based solid acids as
catalyst for the synthesis of 4(3H)-quinazolinones.
Compounds with biological activity are often de-
rived from heterocyclic structures. 4(3H)-Quinazoli-
nones are one such class of bioactive fused heterocycles
1
2
that are widely used as antimalarial, antibacterial, and
3
anticancer drugs. In addition, quinazolinone moiety is a
building block for approximately 150 naturally occur-
4
5
ring alkaloids, such as glycosminine, deoxyvasicinone,
Due to our interest in the synthesis of heterocyclic
6
7
and drugs like methaqualone and piriqualone. There
19-23
compounds,
and in continuation of our previous
are several methods for the synthesis of 4(3H)-quina-
works on the applications of reusable acid catalysts in
8
9
10
13
zolinones using
I
2/KI,
Yb(OTf)
3
,
NaHSO
3
,
24-31
organic reactions,
herein we wish to report the new
11
12
P-toluenesulfunic acid/DDQ, TBAB, SnCl
4
•4H O,
2
efficiently synthesis of 4(3H)-quinazolinones catalyzed
by carbon-based solid acid (Scheme 1).
1
4
and SiO
2
•FeCl
3
as catalysts. However, most of these
multi-step procedures have significant drawbacks such
as long reaction times, low yields of the products, harsh
reaction conditions, difficult work-up, and the use of
expensive and environmentally toxic catalysts, reagents,
or media. Furthermore, some of the starting materials
have to be synthesized and purified first, hence these
methods are time-consuming. Therefore, the develop-
ment of simple and efficient methods for the synthesis
of 4(3H)-quinazolinones is desirable.
Scheme 1
O
O
N
O
Carbon based-solid acid
NH
Ar
NH2
+
Ar
Cl
NH2
1
2a - 2i
3a - 3i
Experimental
Replacement of conventional toxic and pollutant
Brønsted and Lewis acid catalysts with environmentally
benign and reusable solid heterogeneous catalysts is an
active area of current research. New catalysts may in-
clude acidic zeolites, sulfated zirconia and acidic groups
containing resins. Using solid acid catalyst has some
advantages such as low of equipments, ease of products
separation, recycling of the catalyst and environmental
All chemicals were available commercially and used
without additional purification. The catalyst was syn-
thesized according to the literature. Melting points were
recorded on an electrothermal type 9100 melting point
apparatus. The IR spectra were obtained using a 4300
Shimadzu spectrophotometer as KBr disks. The
1
H
NMR (100 & 500 MHz) spectra were recorded with a
Bruker DRX500 & AC100 spectrometers.
15
acceptability as compared to liquid acid catalyst.
Moreover, ideal solid acid catalysts should have high
stability and numerous strong protonic acid sites. Car-
bon-based solid acid catalyst with having such proper-
ties can be successfully used instead of liquid acid cata-
Preparation of carbon-based solid acid
The carbon-based solid acid was prepared according
to the reported procedure by Hara and co-workers.
16
*
E-mail: niloofartavakoli@mshdiau.ac.ir
Received November 5, 2010; revised April 28, 2011; accepted May 3, 2011.
Chin. J. Chem. 2011, 29, 1685— 1688
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1685

Tavakoli-Hoseini & Davoodnia
FULL PAPER
Naphthalene (20 g) was heated in concentrated sulfuric
Table 1 Results of the synthesis of 2-phenyl-4(3H)-quinazoli-
none 3a under different conditions
a
acid (＞96%, 200 mL) at 250 ℃ under a flow of N
2
.
After heating for 15 h, excess sulfuric acid was removed
from the dark brown tar by vacuum distillation at 250
Amount of carbon-
b
Entry
T/℃ Time/min Yield /%
based solid acid/g
None
0.04
℃
for 5 h, which resulted in a black solid. The solid
1
2
3
4
5
6
7
8
9
78
r.t
60
60
60
60
45
45
40
40
40
30
40
30
20
20
20
Trace
26
35
40
49
62
66
59
68
75
67
77
88
88
89
was then ground to a powder and was washed repeat-
edly in boiling water until impurities such as sulfate
ions were no longer detected in the wash water. The
0.04
55
78
r.t
density of the SO
0.01 mol/L) as titrant by acid-base potentiometric titra-
tion. The amount of SO H attached to the polycyclic
3
H group was measured using NaOH
0.04
(
0.08
3
0.08
55
78
r.t
aromatic carbon was 2.84 mmol/g.
0.08
General procedure for the synthesis of 4(3H)-quina-
zolinones catalyzed by carbon-based solid acid
0.10
0.10
55
78
r.t
A mixture of 2-aminobenzamide (2 mmol), aroyl
chloride (2 mmol) and carbon-based solid acid (0.12 g)
as catalyst in ethanol (2 mL) was heated under reflux for
the appropriate time. The reaction was monitored by
TLC. After completion of the reaction, the catalyst was
separated by filteration. The product was collected from
the filtrate after cooling to room temperature and re-
crystallized from ethanol to give compounds 3a—3i in
good to high yields.
1
0
0.10
11
0.12
1
1
2
3
0.12
55
78
78
78
0.12
14
0.14
1
5
0.16
a
b
2
mmol 2-aminobenzamide, 2 mmol benzoyl chloride in ethanol.
Isolated yields.
Recycling and reusing of the catalyst
3 2
THF, CH CN, H O and also in solvent-free conditions.
The catalyst is insoluble in hot ethanol and could
therefore be recycled by a simple fitration. The sepa-
rated catalyst was washed with ethanol, dried at 60 ℃
under vacuum for 1 h and reused in another reaction
without appreciable reduction in the catalytic activity.
In last cases, some starting materials were recycled and
increasing the time of the reaction did not increase the
yield of the product. Although there is no significant
difference between EtOH and n-PrOH as solvent in the
model reaction, howevere, EtOH was selected as sol-
vent in all subsequent reactions.
Results and discussion
At the outset, the synthesis of compound 3a was se-
lected as a model reaction to optimize the reaction con-
ditions. Therefore, 2-aminobenzamide 1 with benzoyl
chloride 2a were reacted in ethanol in the presence of
various amount of carbon based solid acid as catalyst.
The efficiency of the reaction is mainly affected by the
amount of the catalyst (Table 1). It showed that a trace
amount of product could be detected in the absence of
this catalyst in refluxing ethanol (Entry 1), which indi-
cated that the catalyst should be necessary for this
cyclocondensation reaction. When the amount of the
catalyst was increased, a ramp in the yield of the prod-
uct 3a was observed. The optimal amount of the catalyst
was 0.12 g (Entry 13); increasing the amount of the
catalyst beyond this value did not increase the yield no-
ticeably (Entries 14, 15).
Table 2 Synthesis of 2-phenyl-4(3H)-quinazolinone 3a in the
presence of carbon-based solid acid (0.12 g) in different solvents
at reflux temperature (for Entry 8 at 100 ℃)
a
Entry
Solvent
MeOH
EtOH
Time/min
Yield /%
63
1
2
3
4
5
6
7
8
30
20
20
60
45
40
30
25
88
n-PrOH
CH Cl
87
2
2
58
THF
50
CH CN
56
3
H O
2
54
Solvent-free
52
a
Isolated yields.
Furthermore, the reaction was carried out in ethanol
at different temperatures to assess the effect of tem-
perature on the reaction yield. As can be seen from Ta-
ble 1, the shortest time and best yield were achieved in
reflux conditions.
Also, the reaction was carried out in other solvents
and under solvent-free conditions. As shown in Table 2,
the compound 3a was obtained in high yield in EtOH
Encouraged by this success, we extended the reac-
tion of 2-aminobenzamide with a range of other aroyl
chlorides under the optimized reaction conditions. In all
cases the expected products were obtained in high yields
in short reaction times. The results are summarized in
Table 3. As shown, aroyl chlorides with substituents
carrying either electron-donating or electron-with-
drawing groups reacted successfully and gave the prod-
ucts in high yields.
2 2
and n-PrOH but in moderate yields in MeOH, CH Cl ,
1
686
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1685— 1688

A Carbon Material as a Strong Protonic Acid for Synthesis of 4(3H)-Quinazolinones
Table 3 Synthesis of 4(3H)-quinazolinones 3a—3i in the presence of carbon-based solid acid (0.12 g) in ethanol at reflux conditions
a
b
Entry
1
Aroyl chloride
Product
Time/min
20
Yield /%
m.p./℃
O
O
NH
8
Cl
88
93
234—236 [Lit. ]
N
3
a
O
O
NH
8
2
Cl
15
317—319 [Lit. ]
N
Br
Br
3b
O
O
NH
8
3
4
5
Cl
15
20
20
92
87
86
304—307 [Lit. ]
N
Cl
Cl
3
c
O
O
NH OMe
8
Cl
210—218 [Lit. ]
N
OMe
3
d
O
N
O
NH
Cl
OMe
8
213—215 [Lit. ]
OMe
3
e
O
O
NH
8
6
7
Cl
18
15
89
91
248—250 [Lit. ]
N
MeO
OMe
3
f
O
O
NH
8
Cl
242—243 [Lit. ]
N
Me
Me
3
g
O
O
NH
Cl
8
8
9
NO2
13
14
94
92
352—354 [Lit. ]
N
NO2
3
h
O
N
O
NH
8
Cl
362—365 [Lit. ]
O N
2
NO2
3
i
a
All the products were characterized by IR spectral data and comparision of their melting points with those of authentic samples. Also,
1
b
the structures of some products were confirmed by H NMR spectral data. Isolated yields
Chin. J. Chem. 2011, 29, 1685— 1688
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1687

Tavakoli-Hoseini & Davoodnia
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0
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6
In conclusion, although other procedures for the
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Acknowledgements
The authors are thankful to Islamic Azad University,
Mashhad Branch for financial support.
21 Bakavoli, M.; Davoodnia, A.; Rahimizadeh, M.; Heravi, M.
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1685— 1688