Reaction of isatoic anhydride, amine, and N,N′-dialkyl carbodiimides under solvent-free conditions: New and efficient synthesis of 3-alkyl-2-(alkylamino) quinazolin-4(3H)-ones

Article abstract of DOI:10.1080/00397911.2012.714042

Heating a mixture of isatoic anhydride, amines, and N,N′-dialkyl carbodiimides under solvent-free conditions provided novel 3-alkyl-2- (alkylamino)quinazolin-4(3H)-one derivatives for the first time. The products were obtained in moderate to good yields without formation of any by-products. Copyright

Full text of DOI:10.1080/00397911.2012.714042

This article was downloaded by: [Pennsylvania State University]
On: 11 June 2013, At: 12:59
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Reaction of Isatoic Anhydride, Amine,
and N,N′-Dialkyl Carbodiimides Under
Solvent-Free Conditions: New and
Efficient Synthesis of 3-Alkyl-2-
(alkylamino)quinazolin-4(3H)-ones
Mehdi Asadi a , Mostafa Ebrahimi b , Mohammad Mahdavi c , Mina
Saeedi c , Parviz Rashidi Ranjbar a , Farshad Yazdani b , Abbas
Shafiee c & Alireza Foroumadi c d
a School of Chemistry, University College of Science, University of
Tehran , Tehran , Iran
b Chemistry and Chemical Engineering Research Center of Iran ,
Tehran , Iran
c Department of Medicinal Chemistry, Faculty of Pharmacy and
Pharmaceutical Sciences Research Center , Tehran University of
Medical Sciences , Tehran , Iran
d Drug Design and Development Research Center, Tehran University
of Medical Sciences , Tehran , Iran
Accepted author version posted online: 26 Mar 2013.Published
online: 03 Jun 2013.
To cite this article: Mehdi Asadi , Mostafa Ebrahimi , Mohammad Mahdavi , Mina Saeedi , Parviz
Rashidi Ranjbar , Farshad Yazdani , Abbas Shafiee & Alireza Foroumadi (2013): Reaction of Isatoic
Anhydride, Amine, and N,N′-Dialkyl Carbodiimides Under Solvent-Free Conditions: New and Efficient
Synthesis of 3-Alkyl-2-(alkylamino)quinazolin-4(3H)-ones, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 43:17, 2385-2392
To link to this article: http://dx.doi.org/10.1080/00397911.2012.714042
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions

This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 43: 2385–2392, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.714042
REACTION OF ISATOIC ANHYDRIDE, AMINE,
AND N,N ’-DIALKYL CARBODIIMIDES UNDER
SOLVENT-FREE CONDITIONS: NEW AND EFFICIENT
SYNTHESIS OF 3-ALKYL-2-(ALKYLAMINO)
QUINAZOLIN-4(3H)-ONES
Mehdi Asadi,1 Mostafa Ebrahimi,2 Mohammad Mahdavi,3
Mina Saeedi,3 Parviz Rashidi Ranjbar,1 Farshad Yazdani,2
Abbas Shafiee,3 and Alireza Foroumadi3,4
1School of Chemistry, University College of Science, University of Tehran,
Tehran, Iran
2Chemistry and Chemical Engineering Research Center of Iran,
Tehran, Iran
3Department of Medicinal Chemistry, Faculty of Pharmacy and
Pharmaceutical Sciences Research Center, Tehran University of Medical
Sciences, Tehran, Iran
4Drug Design and Development Research Center,
Tehran University of Medical Sciences, Tehran, Iran
GRAPHICAL ABSTRACT
Abstract Heating a mixture of isatoic anhydride, amines, and N,N0-dialkyl carbodiimides
under solvent-free conditions provided novel 3-alkyl-2-(alkylamino)quinazolin-4(3H)-one
derivatives for the first time. The products were obtained in moderate to good yields without
formation of any by-products.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords 3-Alkyl-2-(alkylamino)quinazolin-4(3H)-ones; isatoic anhydride; N,N0-dialkyl
carbodiimides; solvent-free
Received May 23, 2012.
Address correspondence to Alireza Foroumadi, Department of Medicinal Chemistry, Faculty of
Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences,
Tehran 14176, Iran. E-mail: aforoumadi@yahoo.com
2385

2386
M. ASADI ET AL.
INTRODUCTION
Quinazolin-4(3H)-one and their derivatives are very important heterocycles in
medicinal chemistry and have notable pharmacological and therapeutic activities
such as antiulcer,[1] anti-inflammatory,[2] anticancer,[3] hypolipidemic,[4] and anticon-
vulsant properties.[5] Also the quinazolin-4(3H)-one skeleton is found in a range of
biologically important natural products including febrifugine and isofebrifugine
(Fig. 1), which possess antimalarial activity.[6,7]
Because of the prevalent medicinal applications of quinazolin-4(3H)-ones,
attempts to design new protocols for the synthesis of them has increased. So far,
the most common synthetic methods for the preparation of quinazolin-4(3H)-ones
involve (i) reaction of nitriles with lithiated anthranilamides;[8] (ii) condensation of
aldehydes and anthranilamide or its derivatives in the presence of CuCl2;[9] (iii)
microwave-assisted condensation of anthranilic acids, carboxylic acids, and
amines;[10] (iv) condensation of imidates with anthranilic acids;[11] (v) CuI-catalyzed
coupling=condensative cyclization of ortho-haloarylcarboxamides with imida-
mides;[12] (vi) palladium-catalyzed cyclocarbonylation of ortho-iodoanilines with
imidoyl chlorides and carbon monoxide;[13] (vii) silica sulfuric acid catalyzed reaction
of isatoic anhydride, orthoesters, and primary amines;[14] and (viii) amine-induced
thermal rearrangement of iminobenzoxazines.[15]
Among the various routes for the synthesis of complex scaffolds by cascade
reactions, using green chemistry protocols has attracted synthetic organic chemists’
interest. It offers efficient use of energy, hazard reduction, waste minimization, and
the use of renewable resources.[16] Green chemistry was borne in mind and a novel
route for the preparation of quinazolin-4(3H)-ones was designed according to
Scheme 1.
Figure 1. Febrifugine (A) and isofebrifugine (B).
Scheme 1. Synthesis of 3-alkyl-2-(alkylamino)quinazolin-4(3H)-ones 4.

3-ALKYL-2-(ALKYLAMINO)QUINAZOLIN-4(3H)-ONES
2387
RESULTS AND DISCUSSION
In continuation of our ongoing efforts to develop novel routes to synthesize
new heterocycles and bioactive compounds,[17–19] herein, we have described green
synthesis of quinazolin-4(3H)-one derivatives 4 by the solvent-free reaction of
isotonic anhydride 1, amines 2, and N,N0-dialkyl carbodiimides 3 (Scheme 1).
Chemistry of isatoic anhydride and its reaction with amines has been investi-
gated in detail.[20,21] We found that isatoic anhydride undergoes ring opening upon
heating with various amines (Table 1) to produce 2-amino-N-alkylbenzamides.
Moreover, benzamides can easily react with N,N0-dialkyl carbodiimides as potential
Table 1. Synthesis of 3-alkyl-2-(alkylamino)quinazolin-4(3H)-ones 4
2
R -N
2
Entry
R1-NH2
Product
Yield (%)a
=
=
C N-R
1
85
2
82
3
4
80
78
5
6
86
74
7
8
77
84
aIsolated yields.

2388
M. ASADI ET AL.
precursors for nucleophilic attack. Hence, to obtain the best reaction conditions we
initialized with reaction of isatoic anhydride (1 mmol) and benzylamine (1 mmol) at
150 ꢀC under solvent-free conditions. After the completion of reaction (checked by
thin-layer chromatography TLC), N,N0-dicyclohexyl carbodiimide (1.3 mmol) was
added to the reaction mixture, which continued at the same temperature, and after
2 h the related product was obtained in 85% yield. It should be noted that using a
stoichiometric amount of N,N0-dicyclohexyl carbodiimide led to a lower yield, and
excess amount of it is needed.
The structure of product 4a was elucidated by usual spectroscopic analysis. In
the infrared (IR) spectrum, the amide carbonyls showed absorption at 1660 cmꢁ1
and the imine group displayed its characteristic signal at 1615 cmꢁ1. In the 1H
NMR spectrum, the cyclohexyl protons were observed as multiplets at d ¼ 1.09–
1.80 (10H) and d ¼ 1.09–1.80 (1H, NCH) ppm. Doublet signals for cyclohexyl NH
group and singlet signal associated with the two protons of CH2 were visible at
d ¼ 6.41 and 5.40 ppm, respectively. Multiplet signals related to nine aromatic pro-
tons were observed around 7.09–7.96 ppm. The 13C spectrum showed 18 distinct
resonances. The structure was also confirmed by mass spectroscopy fragmentation
pattern analysis, which displayed the molecular ion peak at 333 for C21H23N3O.
The spectrum showed a strong peak at 251, which is related to elimination of the
cyclohexyl ring. The peaks at 222 and 149 have been resulted from loss of carbonyl
and phenyl groups respectively from the latter ion. They are related to the formation
of benzylidene-2-phenylguanidine ion and benzylguanidine radical cation.
After confirmation of 4a and with the optimized conditions in hand for the
synthesis of 3-benzyl-2-(cyclohexylamino)quinazolin-4(3H)-one, we next set out to
explore the scope of our reaction. To our delight, various amines and N,N0-dialkyl
carbodiimides produced diverse quinazolin-4(3H)-one derivatives in good to
excellent yields (Table 1).
Sequences in the formation of compounds 4 are given in Scheme 2. It is
believed that the initial event is the formation of 2-amino-N-alkylbenzamides 5 from
the reaction of isatoic anhydride 1 and amines 2. Then N,N0-dialkyl carbodiimides 3
is added to 5. Cyclization of the intermediate, omission of -NHR2, and tautomeriza-
tion lead to the formation of 3-alkyl-2-(alkylamino)quinazolin-4(3H)-ones 4.
Scheme 2. Steps of the formation of 3-alkyl-2-(alkylamino)quinazolin-4(3H)-ones 4.

3-ALKYL-2-(ALKYLAMINO)QUINAZOLIN-4(3H)-ONES
2389
In conclusion, we have developed a simple and highly efficient green protocol
for the synthesis of potential pharmaceutically active quinazolin-4(3H)-one deriva-
tives by reaction of isatoic anhydride, amines, and N,N0-dialkyl carbodiimides under
solvent-free conditions. The advantages of this work are green procedure, simple
workup, good yields, and versatility, which make it one of the most convenient
methods for the synthesis of this class of heterocycles.
EXPERIMENTAL
Melting points were taken on a Kofler hot-stage apparatus and are uncor-
1
rected. H and 13C NMR spectra were recorded on Bruker FT-500, using tetra-
methylsilane (TMS) as an internal standard. The infrared (IR) spectra were
obtained on a Shimadzu 470 spectrophotometer (potassium bromide disks). Mass
spectra were documented on an Agilent Technology (HP) mass spectrometer operat-
ing at an ionization potential of 70 eV. The elemental analysis was performed with an
Elemetar Analysensystem GmbH VarioEL CHNS mode.
Synthesis of 3-Alkyl-2-(alkylamino)quinazolin-4(3H)-ones:
General Procedure
A mixture of isotonic anhydride 1 (1 mmol) and appropriate amine 2 (1 mmol)
was stirred at 150 ꢀC for 3 h. Then, N,N0-dialkyl carbodiimide 3 (1.3 mmol) was
added to the reaction mixture and stirring continued at 150 ꢀC for 2 h. After com-
pletion of the reaction, it was cooled to room temperature and the residue was pur-
ified by column chromatography using petrolume ether–ethyl acetate (2:1) as eluent.
3-Benzyl-2-(cyclohexylamino)quinazolin-4(3H)-one (4a)
White powder (0.28 g, 85%), mp 148–150 ꢀC. IR (KBr) (nmax=cmꢁ1): 3403,
3109, 2929, 2853, 1660, 1615, 1531, 1473. 1H NMR (500 MHz, DMSO-d6): d
7.96–7.10 (m, 9H, ArH), 6.40 (d, J ¼ 7.4 Hz, 1H, NH), 5.40 (s, 2H, CH2), 3.97 (m,
1H, NCH), 1.80–1.09 (m, 10H, cyclohexyl). 13C NMR (125 MHz, DMSO-d6): d
162.0, 149.3, 149.0, 136.4, 134.2, 128.4, 127.1, 126.7, 126.6, 124.5, 121.6, 116.1,
50.0, 42.8, 33.4, 31.9, 25.3, 24.7. Mass, m=z (%): 333 (Mþ, 31), 251 (100), 222 (30),
91 (50). Anal. calcd. for C21H23N3O: C, 75.65; H, 6.95; N, 12.60%. Found: C,
75.50; H, 7.10; N, 12.55.
3-(4-Chlorobenzyl)-2-(cyclohexylamino)quinazolin-4(3H)-one (4b)
White powder (0.30 g, 82%), mp 177–178 ꢀC. IR (KBr) (nmax=cmꢁ1): 3370,
3056, 2926, 2851, 1661, 1613, 1535, 1470. 1H NMR (500 MHz, DMSO-d6): d
7.94–7.10 (m, 8H, ArH), 6.44 (d, J ¼ 7.5 Hz, 1H, NH), 5.37 (s, 2H, CH2), 3.954
(m, 1H, NCH), 1.82–1.11 (m, 10H, cyclohexyl). 13C NMR (125 MHz, DMSO-d6):
d 161.9, 149.3, 148.9, 135.4, 134.2, 131.7, 128.6, 128.3, 126.5, 124.5, 121.6, 116.0,
50.0, 42.2, 33.3, 31.9, 25.3, 24.7, 24.4. Mass, m=z (%): 369 ([M þ 2]þ, 19), 367
(Mþ, 57), 285 (100), 256 (55), 224 (45), 125 (96). Anal. calcd. for C21H22ClN3O:
C, 68.56; H, 6.03; N, 11.42%. Found: C, 68.20; H, 6.15; N, 11.71.

2390
M. ASADI ET AL.
2-(Isopropylamino)-3-((pyridin-2-yl)methyl)quinazolin-4(3H)-one (4c)
White powder (0.23 g, 80%), mp 165–167 ꢀC. IR (KBr) (nmax=cmꢁ1): 3402,
3050, 2928, 2850, 1660, 1615, 1531, 1475. 1H NMR (500 MHz, DMSO-d6): d
8.51–7.10 (8H, m, ArH), 7.00 (1H, d, J ¼ 7.1 Hz, NH), 5.38 (2H, s, CH2), 4.27
(1H, q, J ¼ 6.5 Hz, CH), 1.16 (6H, d, J ¼ 6.5 Hz, CH3). 13C NMR (125 MHz,
DMSO-d6): d 161.8, 155.5, 149.8, 149.4, 148.7, 137.3, 134.2, 126.5, 124.5, 122.8,
122.4, 121.6, 116.2, 45.5, 42.9, 22.2. Mass, m=z (%): 294 (Mþ, 54), 251 (44), 235
(42), 202 (100), 93 (85). Anal. calcd. for C17H18N4O: C, 69.37; H, 6.16; N,
19.03%. Found: C, 69.50; H, 6.22; N, 19.15.
3-((Furan-2-yl)methyl)-2-(isopropylamino)quinazolin-4(3H)-one (4d)
White powder (0.22 g, 78%), mp 170–172 ꢀC. IR (KBr) (nmax=cmꢁ1): 3407,
1
2925, 3056, 1665, 1530, 1475. H NMR (500 MHz, DMSO-d6): d 7.93–6.60 (m,
7H, ArH), 6.40 (d, J ¼ 7.0 Hz, 1H, NH), 5.38 (d, J ¼ 14.5 Hz, 2H, CH2), 4.30 (q,
J ¼ 6.5 Hz, 1H, CH), 1.20 (d, J ¼ 6.5 Hz, 3H, CH3), 1.12 (d, J ¼ 6.5 Hz, 3H, CH3).
13C NMR (125 MHz, DMSO-d6): d 161.5, 149.3, 149.0, 148.8, 128.7, 128.4, 126.5,
124.5, 124.4, 121.7, 110.5, 108.4, 43.1, 42.3, 22.1, 22.0. Mass, m=z (%): 283 (Mþ,
50), 240 (40), 225 (35) 202 (100). Anal. calcd. for C16H17N3O2: C, 67.83; H, 6.05;
N, 14.83%. Found: C, 67.70; H, 6.30; N, 14.60.
2-(Cyclohexylamino)-3-((furan-2-y)methyl)quinazolin-4(3H)-one (4e)
White powder (0.28 g, 86%), mp 130–131 ꢀC. IR (KBr) (nmax=cmꢁ1): 3403,
3106, 2929, 2853, 1656, 1612, 1558, 1472. 1H NMR (500 MHz, DMSO-d6): d
7.93–7.08 (m, 5H, ArH), 6.50 (d, J ¼ 7.5 Hz, 1H, NH), 6.41–6.38 (m, 2H, furan),
5.41 (s, 2H, CH2), 3.99 (m, 1H, NCH), 1.90–1.04 (m, 10H, cyclohexyl). 13C NMR
(125 MHz, DMSO-d6): d 161.5, 149.4, 149.2, 148.7, 142.5, 134.2, 126.5, 124.4,
121.5, 116.0, 110.4, 108.4, 50.0, 36.5, 33.3, 32.0, 25.3, 24.7, 24.4. Mass, m=z (%):
323 (Mþ, 52), 241 (90), 212 (100), 143 (37). Anal. calcd. for C19H21N3O2: C,
70.57; H, 6.55; N, 12.99%. Found: C, 70.75; H, 6.73; N, 13.10.
3-(2-Chlorobenzyl)-2-(cyclohexylamino)quinazolin-4(3H)-one (4f)
White powder (0.27 g, 74%), mp 129–130 ꢀC. IR (KBr) (nmax=cmꢁ1): 3439,
3060, 2933, 2855, 1678, 1606, 1568, 1475. 1H NMR (500 MHz, DMSO-d6): d
7.89–6.73 (8H, m, ArH), 6.66 (1H, d, J ¼ 7.5 Hz, NH), 5.35 (2H, s, CH2), 4.05
(1H, m, NCH), 1.92–1.06 (10H, m, cyclohexyl). 13C NMR (125 MHz, DMSO-d6):
d 161.7, 149.4, 149.3, 134.3, 133.7, 131.9, 129.4, 128.5, 127.3, 126.4, 126.1, 125.6,
124.6, 115.9, 50.1, 41.9, 32.0, 28.1, 25.6, 25.3, 24.9. Mass, m=z (%): 369 ([M þ 2]þ,
17), 367 (Mþ, 23), 336 (92), 303 (42), 149 (34), 125 (100). Anal. calcd. for
C21H22ClN3O: C, 68.56; H, 6.03; N, 11.42%. Found: C, 68.44; H, 6.20; N, 11.33.
3-(4-Methoxybenzyl)-2-(isopropylamino)quinazolin-4(3H)-one (4g)
White powder (0.25 g, 77%), mp 169–170 ꢀC. IR (KBr) (nmax=cmꢁ1): 3440,
3050, 2925, 2855, 1670, 1612, 1560, 1475. 1H NMR (DMSO-d6): d 7.93–6.88

3-ALKYL-2-(ALKYLAMINO)QUINAZOLIN-4(3H)-ONES
2391
(m, 8H, ArH), 6.52 (d, J ¼ 6.7 Hz, 1H, NH), 5.29 (s, 2H, CH2), 4.27 (q, J ¼ 6.0 Hz,
1H, NCH), 3.70 (s, 3H, OCH3), 1.14 (d, J ¼ 6.0 Hz, 6H, CH3). 13C NMR (125 MHz,
DMSO-d6): d 161.9, 158.4, 149.2, 149.0, 134.2, 128.4, 126.5, 124.4, 121.6, 116.1,
113.8, 55.0, 43.0, 42.1, 40.6, 22.0. Mass, m=z (%): 323 (Mþ, 50), 280 (45), 265 (40),
202 (100). Anal. calcd. for C19H21N3O2: C, 70.57; H, 6.55; N, 12.99%. Found: C,
70.40; H, 6.84; N, 12.84.
3-(3,4-Dimethoxyphenylethyl)-2-(isopropylamino)quinazolin-4(3H)-
one (4h)
White powder (0.31 g, 84%), mp 178–180 ꢀC. IR (KBr) (nmax=cmꢁ1): 3435,
3055, 2920, 2850, 1668, 1610, 1565, 1470. 1H NMR (500 MHz, DMSO-d6): d
7.91–6.72 (7H, m, ArH), 6.38 (1H, d, J ¼ 7.5 Hz, NH), 4.32 (2H, t, J ¼ 7.2 Hz,
CH2), 4.26 (1H, q, J ¼ 6.5 Hz, NCH), 3.70 (3H, s, OCH3), 3.67 (3H, s, OCH3),
2.82 (2H, t, J ¼ 7.2 Hz, CH2), 1.17 (6H, d, J ¼ 6.5 Hz, CH3). 13C NMR (125 MHz,
DMSO-d6): d 161.8, 155.6, 149.8, 149.4, 148.7, 137.3, 134.2, 126.5, 124.5, 122.8,
122.4, 121.6, 116.2, 45.5, 42.9, 31.8, 22.2. Mass, m=z (%): 367 (Mþ, 50), 324 (45),
308 (45), 202 (100). Anal. calcd. for C21H25N3O3: C, 68.64; H, 6.86; N, 11.44%.
Found: C, 68.54; H, 7.05; N, 11.70.
SUPPORTING INFORMATION
1
Full experimental details and H and 13C NMR spectra are available online.
ACKNOWLEDGMENTS
This research was supported by grants from the research council of Tehran
University of Medical Sciences and Iran National Science Foundation (INSF).
REFERENCES
1. Terashima, K.; Shimamura, H.; Kawase, A.; Tanaka, Y.; Tanimura, T.; Kamisaki, T.;
Ishizuka, Y.; Sato, M. Studies on antiulcer agents, IV: Antiulcer effects of
2-benzylthio-5,6,7,8-tetrahydro-4(3H)-quinazolinones and related compounds. Chem.
Pharm. Bull. 1995, 43, 2021–2023.
2. Rather, B. A.; Raj, T.; Reddy, A.; Ishar, M. P. S.; Sivakumar, S.; Paneerselvam, P.
Synthesis and evaluation of novel 2-substituted-quinazolin-4(3H)-ones as potent analgesic
and anti-inflammatory agents. Arch. Pharm. Chem. Life Sci. 2010, 343, 108–113.
3. Cao, S. L.; Feng, Y. P.; Jiang, Y. Y.; Liu, S. Y.; Ding, G. Y.; Li, R. T. Synthesis and
in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side
chains. Bioorg. Med. Chem. Lett. 2005, 15, 1915–1917.
4. Kurogi, Y.; Inoue, Y.; Tsutsumi, K.; Nakamura, S.; Nagao, K.; Yohsitsugu, H.; Tsuda, Y.
Synthesis and hypolipidemic activities of novel 2-[4-[(diethoxyphosphoryl)methyl]phenyl]
quinazolines and 4(3H)-quinazolinones. J. Med. Chem. 1996, 39, 1433–1437.
5. Wolfe, J. F.; Rathman, T. L.; Sleevi, M. C.; Campbell, J. A.; Greenwood, T. D. Synthesis
and anticonvulsant activity of some new 2-substituted 3-aryl-4(3H)-quinazolinones.
J. Med. Chem. 1990, 33, 161–166.

2392
M. ASADI ET AL.
6. Koepfli, J. B.; Mead, J. F.; Brockman Jr., J. A. An alkaloid with high antimalarial activity
from dichroa febrifuga. J. Am. Chem. Soc. 1947, 69, 1837–1837.
7. Kobayashi, S.; Ueno, M.; Suzuki, R.; Ishitani, H. Catalytic asymmetric synthesis of
febrifugine and isofebrifugine. Tetrahedron Lett. 1999, 40, 2175–2178.
8. Couture, A.; Cornet, H.; Grandclaudon, P. An expeditious synthesis of 2-aryl- and
2-alkylquinazolin-4(3H)-ones. Synthesis 1991, 1009–1010.
9. Abdel-Jalil, R. J.; Voelter, W.; Saeed, M. A novel method for the synthesis of 4(3H)-
quinazolinones. Tetrahedron Lett. 2004, 45, 3475–3476.
10. Liu, J. F.; Lee, J.; Dalton, A. M.; Bi, G.; Yu, L.; Baldino, C. M.; McElory, E.; Brown, M.
Microwave-assisted one-pot synthesis of 2,3-disubstituted 3H-quinazolin-4-ones. Tetra-
hedron Lett. 2005, 46, 1241–1244.
11. Connolly, D. J.; Guiry, P. J. A facile and versatile route to 2-substituted-4
(3H)-quinazolinones and quinazolines. Synlett 2001, 1707–1710.
12. Zhou, J.; Fu, L.; Lv, M.; Liu, J.; Pei, D.; Ding, K. Copper(I) iodide–catalyzed domino
process to quinazolin-4(3H)-ones. Synthesis 2008, 3974–3980.
13. Zheng, Z.; Alper, H. Palladium-catalyzed cyclocarbonylation of o-iodoanilines with
imidoyl chlorides to produce quinazolin-4(3H)-ones. Org. Lett. 2008, 10, 829–832.
14. Salehi, P.; Dabiri, M.; Zolfigol, M. A.; Baghbanzadeh, M. A new approach to the facile
synthesis of mono- and disubstituted quinazolin-4(3H)-ones under solvent-free con-
ditions. Tetrahedron Lett. 2005, 46, 7051–705.
15. Snider, B. B.; Zeng, H. Amine-induced rearrangement of 4-imino-4H-3,1-benzoxazines to
4-quinazolinones via amidine carboxamides. Heterocycles 2003, 61, 173–182.
16. Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice; Oxford University
Press: New York, 1998.
17. Javidnia, A.; Akbarzadeh, T.; Firoozpour, L.; Khoobi, M.; Shafiee, A.; Foroumadi, A.
Synthesis of novel 2-(2-methylsulfonyl-1-methyl-1H-imidazol-5-yl)-5-(alkylsulfonyl)-1,3,4-
thiadiazoles. J. Heterocycl. Chem. 2011, 48, 454–457.
18. Hosseini-Zare, M. S.; Mahdavi, M.; Saeedi, M.; Asadi, M.; Javanshir, S.; Shafiee, A.;
Foroumadi, A. Synthesis of 2,3-diaryl-5H-imidazo[2,1-a]isoindolo-5-ones via the one-pot
reaction of 1,2-diketones, 2-formylbenzoic acids and ammonium acetate. Tetrahedron
Lett. 2012, 53, 3448–3451.
19. Tahghighi, A.; Razmi, S.; Mahdavi, M.; Foroumadi, P.; Ardestani, S. K.; Emami, S.;
Kobarfard, F.; Dastmalchi, S.; Shafiee, A.; Foroumadi, A. Synthesis and anti-leishmanial
activity of 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-amines containing N-[(1-benzyl-1H-
1,2,3-triazol-4-yl)methyl] moieties. Eur. J. Med. Chem. 2012, 50, 124–128.
20. Coppola, G. M. The chemistry of isatoic anhydride. Synthesis 1980, 505–536.
21. Clark, R. H.; Wagner, E. C. Isatoic anhydride, I: Reactions with primary and secondary
amines and with some amides. J. Org. Chem. 1944, 9, 55–67.