A convenient synthesis of substituted quinazolin-4(3H)-ones under microwave and solvent-free conditions

Article abstract of DOI:10.1080/10426500490485606

A clean and facile synthesis of the title compounds is achieved from cyclocondensation of 2-aminobenzamides with orthoesters catalyzed by SiO ₂/H₂SO₄ in dry and microwave conditions.

Full text of DOI:10.1080/10426500490485606

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A CONVENIENT SYNTHESIS
OF SUBSTITUTED
QUINAZOLIN-4(3H)-ONES
UNDER MICROWAVE AND
SOLVENT-FREE CONDITIONS
Nasser Montazeri a & Kurosh Rad-Moghadam b
a Chemistry Department, Islamic Azad University of
Tonekabon, Tonekabon, Iran
b Chemistry Department, Guilan University, Rasht,
Iran
Version of record first published: 16 Aug 2010.
To cite this article: Nasser Montazeri & Kurosh Rad-Moghadam (2004): A CONVENIENT
SYNTHESIS OF SUBSTITUTED QUINAZOLIN-4(3H)-ONES UNDER MICROWAVE AND
SOLVENT-FREE CONDITIONS, Phosphorus, Sulfur, and Silicon and the Related Elements,
179:12, 2533-2536
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Phosphorus, Sulfur, and Silicon, 179:2533–2536, 2004
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490485606
A CONVENIENT SYNTHESIS OF SUBSTITUTED
QUINAZOLIN-4(3H)-ONES UNDER MICROWAVE
AND SOLVENT-FREE CONDITIONS
Nasser Montazeria and Kurosh Rad-Moghadamb
Chemistry Department, Islamic Azad University of Tonekabon,
Tonekabon, Iran;a and Chemistry Department,
Guilan University, Rasht, Iranb
(Received April 13, 2004; accepted May 11, 2004)
A clean and facile synthesis of the title compounds is achieved from
cyclocondensation of 2-aminobenzamides with orthoesters catalyzed by
SiO2/H2SO4 in dry and microwave conditions.
Keywords: Microwave; quinazolin-4(3H)-ones; solvent-free; sulfuric
acid on silica
Natural and synthetic compounds with quinazoline structural mo-
tif have been identified to display a wide range of biological activi-
ties. The prominent potencies associated with quinazoline containing
compounds are their anti-inflamatory,1 anthelmintic,2 analgesic,3 CNS
depressant,4 anticancer,5 and anticonvulsive6 activities. Because of
these widespread activities, their synthesis was continually the subject
of much research7 and is still pursued due to new emerging methods,
such as microwave heating.8 Performing reactions under microwave
irradiation frequently gives rise to some rate enhancement and im-
provement of yields. Microwave condition is best suited to the so-called
solvent-free reactions. These reactions are eco-friendly and, in view of
green chemistry’s desire to avoid solvent hazards, are in demand.
As a finding of our ongoing research projects on the synthesis of
quinazoline derivatives,9 we now report that microwave-assisted cy-
clocondensation of 2-aminobenzamides 1 with orthoesters 2 on silica-
supported sulfuric acid quickly provides the substituted quinazolin-
4(3H)-ones 3 in fairly high yields. To our knowledge, there has been no
Address correspondence to Nasser Montazeri, Chemistry Department, Islamic Azad
University of Tonekabon, Tonekabon, Iran. E-mail: montazer50@yahoo.com
2533

2534
N. Montazeri and K. Rad-Moghadam
report on the use of sulfuric acid adsorbed on silica gel (SiO2/H2SO4) as
a solid catalyst in the synthesis of quinazolines (Scheme 1).
SCHEME 1
The early method, based on the reaction of 2-aminobenzamide with
orthoester, was performed in the presence of H2SO4, and as a require-
ment of its refluxing condition much excess of orthoester was used.10
Although an excess of orthoester is necessary to diminish the inter-
molecular side reactions, the conventional heating method needs addi-
tional orthoester both to act in place of solvent and to improve the yield.
In contrast to the liquid H2SO4, which is difficult to recover and takes
some effort in workup, the silica-supported H2SO4 can be easily sepa-
rated and recycled without the loss of activity for several times. Thus,
2-aminobenzamides 1 reacted with nearly 2 equivalents of orthoesters
2 with the aide of SiO2/H2SO4and submission to microwave irradiation
to provide fairly high yields of substituted quinazolin-4(3H)-ones 3a–i
in a few minutes (Table I). At the same time, in the absence of catalyst
TABLE I Physical Data of the Compounds 3a–3i
Product
R2
R1
Yield (%) f
m.p. (◦C ) Lit. m.p. (◦C)
3a
3b
3c
3d
3e
3f
3g
3h
3i
Ph
Ph
Ph
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
H
CH3
Ph
H
CH3
Ph
H
CH3
Ph
84
85
92
88
90
95
87
92
97
137–138
146–147
158–159
144–145
151–152
180–181
180–181
155–156
190–191
137–138a
147–148b
158c
143–144a
151–152b
180–181c
180–181a
157–158d
189–190e
aRunti et al.11
bErrede et al.12
cLevy and Stephen.13
dGrimmel et al.14
ePetyunin et al.15
f Yields of separated products, based on 2-aminobenzamides, 2.

Quinazolin-4-Ones
2535
or by mixing the catalyst with reactants without exposure to microwave
irradiation, no reaction took place.
In conclusion, in comparison with the previous related methods10,16
which show drawbacks from the standpoints of prolonged refluxing in
solvent, need for inert gas, and consuming more orthoester, the notable
advantages of this methodology are: mild conditions in a solvent-free
system, fairly high yields, fast reaction, no aqueous workup, and safe
and environmental friendly conditions.
EXPERIMENTAL
All products were known compounds and identified by compari-
son with authentic samples. The catalyst is prepared by mixing
chromatographic-grade silica (Merck, Darmstadt, Germany, Kiesel gel,
60, 70–230 mesh) with 3% of its weight of sulfuric acid dissolved in ace-
tone following a reported method.17 2-Aminobenzamides 1 were pre-
pared according to a reported procedure from the readily available
isatoic anhydride and the proper primary amine.18 Melting points were
measured on a Mettler FP5 electrothermal apparatus and are uncor-
rected. Microwave irradiations were carried out in a 700 W domestic
microwave oven at 2450 MHz. In order to control the reaction violence,
irradiations were performed in two stages with a cooling time between
them.
General Procedure
A mixture of 1 (0.005 mole), orthoester 2 (2 ml in each case), and 0.2 g
of finely ground silica-supported sulfuric acid was placed in a 100 ml
beaker. The beaker was covered with a stemless funnel and then irradi-
ated in the microwave oven for 2 min with power of 120 W. After a cool-
ing time of about 3 min to room temperature, the beaker was irradiated
again for 3 min at 120 W. After completion of the reaction (monitored by
thin layer chromatography (TLC) using ethyl acetate: hexane 1:1) the
hot residue was dissolved in 8 ml of ethanol 95%. The solid catalyst was
filtered off, and the fairly pure crystals of products that separated on
cooling from the filtrate solution were further recrystallized in ethanol
95%.
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