Synthesis of 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives using heteropolyacids as green, heterogeneous and recyclable catalysts

Article abstract of DOI:10.1016/j.cclet.2010.10.012

Reaction of isatoic anhydride with aniline derivatives gave 2-amino-N-(aryl)benzamides. The latters reacted with phenylisothiocyanate in the presence of heteropolyacids in various solvents which afforded 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives. The effects of various heteropolyacids including Preyssler and Keggin on the yields and reaction times have been investigated.

Full text of DOI:10.1016/j.cclet.2010.10.012

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 131–134
www.elsevier.com/locate/cclet
Synthesis of 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
derivatives using heteropolyacids as green, heterogeneous
and recyclable catalysts
a,
S. Allameh , M.M. Heravi , M.M. Hashemi , F.F. Bamoharram
b
a
c
*
a
Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
b
Department of Chemistry, School of Sciences, Alzahra University, Vanak,Tehran, Iran
c
Department of Chemistry, Faculty of Sciences, Islamic Azad University, Mashhad Branch, Mashhad, Iran
Received 31 May 2010
Abstract
Reaction of isatoic anhydride with aniline derivatives gave 2-amino-N-(aryl)benzamides. The latters reacted with phenyli-
sothiocyanate in the presence of heteropolyacids in various solvents which afforded 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-
4
(1H)-one derivatives. The effects of various heteropolyacids including Preyssler and Keggin on the yields and reaction times have
been investigated.
2010 S. Allameh. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
#
Keywords: Thioxo-quinazolinones; Recyclable catalysts; Heteropolyacids; Heterogeneous
Heteropolyacids (HPAs) are well defined molecular clusters that are remarkable for their molecular and electronic
structural diversity and their significance is quite diverse in many areas, e.g., catalysis, medicine, and materials science
[
1].
The application of heteropolyacids (HPAs) as catalyst is growing. These compounds possess unique properties such
as: Br o¨ nsted acidity, possibility to modify their acid–base and redox properties by changing their chemical
composition (substituted HPAs), ability to accept and release electrons, high proton mobility, easy work-up
procedures, easy filtration, and minimization of cost and waste generation due to reuse and recycling of these catalysts
[
2–7]. Because of their stronger acidity, they generally exhibit higher catalytic activity than conventional catalysts
such as mineral acids, ion exchange resins, mixed oxides, zeolites, etc. [8]. In view of green chemistry, the substitution
of harmful liquid acids by solid reusable HPAs as catalyst in organic synthesis is the most promising application of
these acids [8,9].
3
-(Aryl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones and their polycyclic derivatives are a very important class of
heterocycles with a wide range of pharmacological and biological activities [10–13]. In spite of their importance from
a pharmaceutical, industrial and synthetic point of view, comparatively few methods for their preparation are reported
*
Corresponding author.
E-mail address: sadegh_allameh@yahoo.com (S. Allameh).
1001-8417/$ – see front matter # 2010 S. Allameh. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.10.012

132
S. Allameh et al. / Chinese Chemical Letters 22 (2011) 131–134
in the literature [14–17,10]. Many of these processes suffer from some limitations such as drastic reaction conditions,
expensive reagents, low to moderate yields and relatively long reaction times. Hence, the development of simple,
efficient, clean, high-yielding and environmentally friendly approaches is desirable. It is therefore of interest to
examine the behavior of some heteropolyacids as catalyst in various solvents for the synthesis of 3-(aryl)-2-thioxo-2,3-
dihydroquinazolin-4(1H)-ones. To the best of our knowledge, condensation of 2-amino-N-(aryl)-benzamides with
phenyl-isothiocyanate in the presence of a catalytic amount of heteropolyacids (HPAs) in various solvents for the
synthesis of 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives has not yet been reported in literature.
Herein we report the catalytic effects of some heteropolyacids in various solvents for the synthesis of 3-(aryl)-2-
thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives.
[TD$INLINE]
R
R
O
O
PhNCS
HPAs
NH
2
O
NH
EtOH
N
H
O
NH2
R
O
N
N
H
S
R=H,Me,Cl,Br
Initially, in order to find the optimal conditions, the reaction of 2-amino-N-(4-methylphenyl)benzamide
0.010 mol) with phenylisothiocyanate (0.015 mol) in the presence of various amount of H [PW O ] in various
(
3
12 40
solvents were used as a model reaction. The best result has been obtained at 0.15 mol% of catalyst in p-xylene.
However, regarding the green chemistry, ethanol is also a good choice as a solvent. To show the generality of this
method the optimized system was used for the synthesis of the 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
derivatives by cyclization 2-amino-N-(aryl)benzamides with phenylisothiocyanate in the various of solvents, i.e., p-
xylene, n-hexane, cyclohexane, toluene, ethanol and chloroform (Table 1), and the presence of catalytic amount of
various type of HPAs including, H [PW O ], H [PMo O ], H [SiW O ], H [NaP W O110] (Table 2).
3
12 40
3
12 40
4
12 40
14
5
30
We also investigated the reusability of the catalyst. For this purpose after completion of the model reaction in
refluxing p-xylene, the mixture was filtrated and ethanol was added to the residue. The catalyst was not soluble in
ethanol and it could be separated by a simple filtration and washed with dichloromethane. The recycled catalyst was
used for three reactions with the same substrate without observation of appreciable loss in its catalytic activity. The
results of the first experiment and subsequent experiments were almost consistent in yields (79, 77 and 74%).
It should be noted that, this method is effective for the preparation of 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-
4
(1H)-one derivatives form reaction of 2-amino-N-(aryl)benzamides with phenylisothiocyanate.
Table 1
3
Synthesis of 3-(4-methylphenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one using H [PW12O40] in different solvents.
Entry
Solvent
Time (min)
Yield%
1
2
3
4
5
6
p-Xylene
n-Hexane
Cyclohexane
Toluene
36
39
40
42
43
45
84
83
83
80
80
77
Ethanol
Chloroform

S. Allameh et al. / Chinese Chemical Letters 22 (2011) 131–134
133
Table 2
Synthesis of 3-(4-methylphenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one using various heteropolyacids in p-xylene.
Entry
Catalyst
Time (min)
Yield%
1
2
3
4
H
H
H
H
14[NaP
5
W
30
40
40
40
O
110
]
35
36
37
40
85
84
84
82
3
4
3
[PW12
[SiW12
[PMo12
O
]
O
]
O
]
In summary, we wish, reporting the use of various heteropolyacids as green recyclable and heterogeneous catalysts
in different solvents for the synthesis of 3-(aryl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones via condensations of 2-
amino-N-(aryl)benzamides with phenylisothiocyanate.
1
. Experimental
All chemicals were obtained from Merck Company and used as received. H [NaP W O110] was prepared
1
4
5
30
according to earlier works [18]. Melting points were determined on an Electrothermal type 9100 melting point
apparatus and are uncorrected. The IR spectra were obtained on a 4300 Shimadzu spectrophotometer as KBr disks.
1
The H NMR (100 MHz) spectra were recorded on a Bruker AC 100 spectrometer. The Mass spectra were recorded on
a Massens Poektometer varian CH-7 at 70 ev mass spectrometer. All products gave satisfactory spectral data in accord
with the assigned structures.
A mixture of 2-amino-N-(aryl)benzamides (0.01 mol), phenylisothiocyanate (0.01 mol) and appropriate
heteropolyacid (0.15 mol %) was refluxed in various solvents for 36–45 min. After completion of reaction
(monitored by TLC, MeOH:CHCl , 1:9) the reaction mixture was cooled and precipitate was filterated and washed
3
with cold solvent to afford the product in good yields. All products gave satisfactory spectral data in accordance with
the assigned structures.
1
3
.8 (m, 9H, Ar-H), 11.8 (br, 1H, N–H exchange with D O), m/z: 252 (M -2), IR (KBr disc): y 1662 (C O), 3243 (NH),
229 cm (C S).
-Phenyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one: mp: 295 8C (Lit. [19] 302 8C), H NMR (DMSO-d ): d 6.4–
6
+
7
1
2
À1
1
3
DMSO-d ): d 2.4 (s, 3H, CH ), 7.2–8.0 (m, 8H, Ar-H), 13 (br, 1H, N–H exchange with D O), m/z: 268 (M ), IR (KBr
-(4-Methylphenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one: mp: 315 8C (Lit. [20] 305–307 8C), H NMR
+
(
6
3
2
À1
À1
disc): y 1662 (C O), 3242 cm (NH), 1229 cm (C S).
-(4-Chlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one: mp: 300 8C (Lit. [21] 317 8C), H NMR (DMSO-
1
3
d ): d 6.9–7.6 (m, 8H, Ar-H), 9.8 (br, 1H, N–H exchange with D O), m/z: 287 (M -1), IR (KBr disc): y 1661 (C O),
+
6
2
À1
À1
3
244 cm (NH), 1233 cm (C S).
-(4-Bromophenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one: mp: 335 8C (Lit. [19] 320 8C), H NMR (DMSO-
1
3
d ): d 7.1–8.0 (m, 8H, Ar-H), 13.1 (br, 1H, N–H exchange with D O), m/z: 334 (M ), IR (KBr disc): y 1662 (C O),
3
+
6
2
À1
À1
245 cm (NH), 1229 cm (C S).
References
[
[
[
[
[
[
[
[
[
1] M. Misono, L. Ono, G. Koyano, et al. Pure Appl. Chem. 72 (2000) 1305.
2] M.M. Heravi, G. Rajabzadeh, et al. J. Mol. Catal. A: Chem. 256 (2006) 238.
3] M.M. Heravi, Kh. Bakhtiari, F.F. Bamoharram, Catal. Commun. 7 (2006) 499.
4] M.M. Heravi, F.F. Bamoharram, et al. J. Mol. Catal. A: Chem. 259 (2006) 213.
5] M.T. Pope, Heteropoly and Isopoly, in: Oxometalates, Springer, Berlin, 1983.
6] M.M. Heravi, Kh. Bakhtiari, F.F. Bamoharram, Catal. Commun. 7 (2006) 373.
7] F.F. Bamoharram, M.M. Heravi, M. Roshani, et al. J. Mol. Catal. A: Chem. 252 (2006) 90.
8] M.M. Heravi, F.F. Bamoharram, et al. J. Mol. Catal. A: Chem. 249 (2006) 1.
9] F.F. Bamoharram, M.M. Heravi, M. Roshani, et al. J. Mol. Catal. A: Chem. 255 (2006) 193.
[
[
[
10] G. Vasilev, R. Vasileva, A. Dokl, Nauk Bolg. 2 (1962) 157.
11] L. Rom, S. Om Prakash, Arch. Pharm. (Weinheim Ger) 318 (3) (1985) 228.
12] T. Aono, F. Maruishogo, M. Yamakoa, Eur. Pat. Appl. EP733, 633 (1996) (Cl.CO7D 87/04).

134
S. Allameh et al. / Chinese Chemical Letters 22 (2011) 131–134
[
[
[
[
[
[
[
[
[
13] M.A. Aziza, M.K. Ibrahim, J. Pharm. Sci. 14 (1994) 290.
14] M. Abdel-Mageed, L. Aly Yossef, et al. Sulfur Lett. 19 (3) (1995) 129.
15] S. Haryit, K. Subodh, Tetrahedron 43 (9) (1987) 2177.
16] S. Palazzo, L. Gannola, J. Heterocycle 12 (5) (1975) 1077.
17] M. Seth, N.M. Kaanna, Indian J. Chem. Sect. B (1976) 335.
18] F.F. Bamoharram, M.M. Heravi, M. Roshani, et al. Appl. Catal. 302 (2006) 318.
19] R. Lakhan, M. Srivastava, J. Chem. Sci. 105 (1) (1993) 11.
20] J. Azizian, A.A. Mohamadi, A.R. Karimi, Synth. Commun. 33 (3) (2003) 415.
21] C.K. Reddy, P.S.N. Reddy, C.V. Ratnam, Indian J. Chem. Sect. B 26B (9) (1987) 882.