An efficient one-pot procedure for preparation of 2,4(1H,3H)-quinazolinediones and 2-thioxoquinazolinone derivatives under microwave irradiation

Article abstract of DOI:10.1081/SCC-120015771

An efficient one-pot synthesis of 2,4(1H,3H)-quinazolinediones and 2-thioxoquinazolinone derivatives are given by the condensation of isatoic anhydride, primary amine and urea or thiourea in the absence of organic or inorganic reagents under microwave irr

Full text of DOI:10.1081/SCC-120015771

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An Efficient One-Pot Procedure for Preparation
of 2,4(1H,3H)-Quinazolinediones and 2-
Thioxoquinazolinone Derivatives Under Microwave
Irradiation
Javad Azizian a , Ali A. Mohammadi a & Ali R. Karimi a
a Department of Chemistry, Faculty of Science, Shahid Beheshti University, Tehran, Iran
Version of record first published: 17 Aug 2006
To cite this article: Javad Azizian, Ali A. Mohammadi & Ali R. Karimi (2003): An Efficient One-Pot Procedure for
Preparation of 2,4(1H,3H)-Quinazolinediones and 2-Thioxoquinazolinone Derivatives Under Microwave Irradiation, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:3, 415-420
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 3, pp. 415–420, 2003
An Efficient One-Pot Procedure for Preparation
of 2,4(1H,3H)-Quinazolinediones and
2-Thioxoquinazolinone Derivatives
Under Microwave Irradiation
*
Javad Azizian, Ali A. Mohammadi, and Ali R. Karimi
Department of Chemistry, Faculty of Science,
Shahid Beheshti University, Tehran, Iran
ABSTRACT
An efficient one-pot synthesis of 2,4(1H,3H)-quinazolinediones and
2-thioxoquinazolinone derivatives are given by the condensation of
isatoic anhydride, primary amine and urea or thiourea in the absence
of organic or inorganic reagents under microwave irradiation.
Various methods for the synthesis of 3-aryl or 3-alkyl-2,4(1H,3H)-
quinazolinediones and 2-thioxoquinazolinones have been reported in a
*Correspondence: Javad Azizian, Department of Chemistry, Faculty of Science,
Shahid Beheshti University, P.O. Box 19395-4716, Tehran, Iran; E-mail:
Javad_azizian@yahoo.com.
415
DOI: 10.1081/SCC-120015771
Copyright & 2003 by Marcel Dekker, Inc.
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416
Azizian, Mohammadi, and Karimi
number of papers, and a literature search reveals that most of these
compounds are prepared by multi-step reactions in presence of acidic,
basic and other reagents[1] or involve different rearrengment reaction with
different starting materials.[2]
The microwave assisted chemical transformations have become
important due to several advantages over the conventional thermal reac-
tions. We have recently described an efficient and rapid synthesis of a
variety of heterocyclic compounds under microwave irradiation in an
unmodified commercial microwave oven.[3] We have also reported the
preparation 2,4(1H,3H)-quinazolinediones derivatives by oxidation of
isatin-3-imines,[4] as a continuation of this work, here we wish to report
a rapid and efficient one-pot procedure microwave-assisted preparation
of 2,4(1H,3H)-quinazolinediones and 2-thioxoquinazolines derivatives.
This procedure occurs in the absence of organic or inorganic reagents
and also the reaction time is reduced from several hours to several
minutes.
We have found that the condensation of isatoicanhydride 10, with
primary amine 20 and urea or thiourea results in rapid formation of the
corresponding quinazolinediones (1–6) and 2-thioxoquinazolinones
(7–12) when the reactions were conducted in open vessels in a microwave
oven (Sch. 1).
It is known that N,N-dimethyl acetamide (DMAC) is an excellent
energy-transfer solvent with a high dielectric constant, thus, it causes to
increase the energy input in a shorter time and it provides a uniform
heating of reaction mixture, there fore a small amount of (DMAC)
was added to the mixture and we found the best reaction conditions
(Table 1).
Scheme 1.

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2,4(1H,3H)-Quinazolinediones
417
Table 1. The reaction of isatoicanhydride with primary amine and urea or
thiourea.
DMAC
(mL)
Yield
(%)a,b
Lit. M.p.
(ꢀC)c
Product
Amine
Methyl
Ph
p-ClC6H4
p-BrC6H4
p-MeC6H4
PhCH2
Methyl
Ph
p-ClC6H4
p-MeC6H4
PhCH2
X
M.p. (ꢀC)
1
2
3
4
5
6
7
8
9
O
O
O
O
O
O
S
S
S
S
S
2
1
3
3
3
2
2
1
3
3
2
2
90
93
75
78
85
78
88
72
73
78
83
80
247–248
283
248–250[5]
282[6]
270[7]
299–301[8]
267–268[9]
227–230[2c]
274–275[5]
307[7]
317[7]
303[10]
253–255[11]
244–245[12]
267–269
299–300
268–269
226–227
272–274
208–209
319–321
305–307
253–254
243–244
10
11
12
PhCH2CH2
S
aTo control the reaction, the irradiation was carried out in two stages, with a
cooling period between each irradiation (irradiation conditions were [1] P/W
210 t/min 2, [2] P/W 385 t/min 8).
bYield of pure isolated product based on isatoicanhydride.
cIn literature, depending on the kind of recrystallization solvent, a wide renge of
melting points have been reported for 3-aryl-2,4-quinazolinediones. For example,
the melting point ranges are 2: 210–306ꢀC; 3: 268–301ꢀC 4: 248–277ꢀC.[4]
EXPERIMENTAL
Melting points were measured on the Electrothermal 9100 apparatus
and are uncorrected. Infrared spectra were measured on a Shimadzu IR-
470 Spectrophotometer. Mass spectra were recorded on a Shimadzu QP
1100 EX Mass Spectrometer operating at an ionization potential of
70 eV. Microwave irradiation were carried out in a National oven,
model 5250, at 2450 MHz.
General Procedure
A mixture of isatoicanhydride (10) (2.45 mmol, 0.4 g), primary amine
(20) (3 mmol), urea or thiourea (2.45 mmol), and 1–3 mL of DMAC
(Table 1) in a tall beaker, the beaker covered with a stemless funnel,

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Azizian, Mohammadi, and Karimi
and was placed in the microwave oven, then irradiated with power and
time as indicated in Table 1. The reaction mixture was allowed to cool to
roomtemperature. Triturating of the crude product with water and
recrystallization fromethanol (96%) gave the desired products.
3-Methyl-2,4(1H,3H )-quinazolinedione (1): White powder. M.p.:
247–248ꢀC (Lit.[5] 248–250ꢀC). IR (KBr): ꢀ max/cmÀ1: 3165 (N-H),
1715, 1662 (2C¼O). M.S. (m/z, %): 176 (Mþ, 80), 146 (Mþ ÀCH3-NH,
10), 119 (Mþ ÀCH3N¼C¼O, 90), 92 (119, –HCN, 55), 64 (92, –CO, 35),
39 (64, –C2H, 20).
3-Phenyl-2,4(1H,3H )-quinazolinedione (2): White powder. M.p.:
283ꢀC (Lit.[6] 282ꢀC). IR (KBr): ꢀ max/cmÀ1: 3250 (N-H), 1740, 1665
(2C¼O). M.S. (m/z, %): 238 (Mþ, 80), 146 (Mþ ÀPh-NH, 50), 119
(Mþ ÀPhN¼C¼O, 85), 92 (119, –HCN, 50), 64 (92, –CO, 20).
3-(4-Chlorophenyl)-2,4(1H,3H )-quinazolinedione (3): White powder.
M.p.: 267–269ꢀC (Lit.[7] 270ꢀC). IR (KBr): ꢀ max/cmÀ1: 3270 (N-H),
1731, 1664 (2C¼O). M.S. (m/z, %): 274 (Mþ þ2, 20), 272 (Mþ, 50), 146
(Mþ ÀClPh-NH, 80), 119 (Mþ ÀClPhN¼C¼O, 85), 92 (119-HCN, 50), 64
(92, –CO, 30).
3-(4-Bromophenyl)-2,4(1H,3H )-quinazolinedione (4): White powder.
M.p.: 299–300ꢀC (Lit.[8] 299–301ꢀC). IR (KBr): ꢀ max/cmÀ1: 3220
(N-H), 1720, 1666 (2C¼O). M.S. (m/z, %): 318 (Mþþ2, 35), 316 (Mþ,
35), 146 (Mþ À BrPh-NH, 65), 119 (Mþ À BrPhN¼C¼O, 80), 92 (119,
–HCN, 55), 63 (119, –CO, 35).
3-(4-Methylphenyl)-2,4(1H,3H )-quinazolinedione (5): White powder.
M.p.: 268–269ꢀC (Lit.[9] 267–268ꢀC). IR (KBr): ꢀ max/cmÀ1: 3210 (N-H),
1719, 1662 (2C¼O). M.S. (m/z, %): 252 (Mþ, 85), 146 (Mþ À MePh-NH,
85), 119 (Mþ À MePhN¼C¼O, 85), 92 (119–HCN, 85), 64 (92, –CO, 40),
39 (64, –C2H, 20).
3-Benzyl-2,4(1H,3H )-quinazolinedione (6): White powder. M.p.:
226–227ꢀC (Lit.[2c] 227–230ꢀC). IR (KBr): ꢀ max/cmÀ1: 3170 (N-H),
1707, 1650 (2C¼O). M.S. (m/z, %): 252 (Mþ, 90), 146 (Mþ ÀPhCH2-
NH, 45), 119 (Mþ À PhCH2N¼C¼O, 30), 91 (119 –CO, 85), 65 (119
–CN, 50), 64 (119 –HCN, 25), 39 (64 –C2H, 30).
3-Methyl-2-thioxo-1,2-dihydro-4(3H )-quinazolinone
(7):
White
powder. M.p.: 272–274ꢀC (Lit.[5] 274–275ꢀC). IR (KBr): ꢀ max/cmÀ1
:
3155 (N-H), 1682 (C¼O), 1160 (C¼S). M.S. (m/z, %): 192 (Mþ, 90),
162 (Mþ À CH3NH, 15), 159 (Mþ À SH, 20), 119 (Mþ À CH3N¼C¼S,
50), 92 (119, –HCN, 30), 64 (92, –CO, 25), 39 (64, –C2H, 20).
3-Phenyl-2-thioxo-1,2-dihydro-4(3H )-quinazolinone
(8):
White
powder. M.p.: 308–309ꢀC (Lit.[7] 307ꢀC). IR (KBr): ꢀ max/cmÀ1: 3220
(N-H), 1661 (C¼O), 1190 (C¼S). M.S. (m/z, %): 254 (Mþ, 90), 221

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2,4(1H,3H)-Quinazolinediones
419
(Mþ À SH, 20), 162 (Mþ À PhNH, 20), 119 (Mþ À PhN¼C¼S, 30), 92
(119, –HCN, 30), 64 (92, –CO, 30), 39 (64, –C2H, 25).
3-(4-Chlorophenyl)-2-thioxo-1,2-dihydro-4(3H )-quinazolinone (9):
White podwer. M.p.: 319–321ꢀC (Lit.[7] 317ꢀC). IR (KBr): ꢀ max/cmÀ1
:
3225 (N-H), 1658 (C¼O), 1197 (C¼S). M.S. (m/z, %): 290 (Mþ þ 2, 30),
288 (Mþ, 90), 255 (Mþ ÀSH, 15), 162 (Mþ À ClPhNH, 25), 119
(Mþ À ClPhN¼C¼S, 35), 92 (119, –HCN, 35), 64 (92, –CO, 30), 39
(64, –C2H, 25).
3-(4-Methylphenyl)-2-thioxo-1,2-dihydro-4(3H )-quinazolinone (10):
White powder. M.p.: 305–307ꢀ C (Lit.[10] 303ꢀC). IR (KBr):
ꢀ max/cmÀ1: 3220 (N-H), 1663 (C¼O), 1193 (C¼S). M.S. (m/z, %):
268 (Mþ, 90), 235 (Mþ À SH, 15), 162 (Mþ À Me PhNH, 25), 119
(Mþ À MePhN¼C¼S, 35), 92 (119, –HCN, 30), 64 (92, –CO, 25), 39
(64, –C2H, 25).
3-Benzyl-2-thioxo-1,2-dihydro-4(3H )-quinazolinone
(11):
White
powder. M.p.: 253–254ꢀC (Lit.[11] 253–255ꢀC). IR (KBr): ꢀ max/cmÀ1
:
3180 (N-H), 687 (C¼O), 1199 (C¼S). M.S. (m/z, %): 270 (Mþ þ 2, 25),
268 (Mþ, 80), 35 (Mþ À SH, 80), 162 (Mþ À PhCH2NH, 30), 119
(Mþ À PhCH2N¼C¼S, 25), 91 (119, –CO, 90), 64 (91, –HCN, 30), 39
(64, –C2H, 35).
3-Phenylethyl-2-thioxo-1,2-dihydro-4(3H )-quinazolinone (12): White
powder. M.p.: 243–244ꢀC (Lit.[12] 244 –245ꢀC). IR (KBr): ꢀ max/cmÀ1
:
3170 (N-H), 1642 (C¼O), 1152 (C¼S). M.S. (m/z, %): 282 (Mþ,
85), 249 (Mþ À SH, 20), 162 (Mþ À phCH2CH2NH, 50), 119
(Mþ À PhCH2CH2N¼C¼S, 50), 91 (119, –CO, 50), 64 (91, –HCN, 25),
39 (64, –C2H, 30).
ACKNOWLEDGMENT
We thank the Vice President of research affairs at the Shahid
Beheshti Uninarsity for financial support.
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Received in the Netherlands January 21, 2002