A green and efficient synthesis of 2-thioxoquinazolinone derivatives in water using potassium thiocyanate

Article abstract of DOI:10.1080/17415993.2017.1325891

Green chemistry is one of the most important routes for the synthesis of heterocyclic compounds. In this regard, the synthesis of 2-thioxoquinazolinone derivatives was achieved by condensation of versatile materials including isatoic anhydride, amine and potassium thiocyanate in the green medium of water. This convenient and ef?cient method affords the desired products with good to excellent yields.

Full text of DOI:10.1080/17415993.2017.1325891

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
A green and efficient synthesis of 2-
thioxoquinazolinone derivatives in water using
potassium thiocyanate
Ghasem Rezanejade Bardajee, Aseyeh Ghaedi, Shohreh Hekmat, Ghazale
Abarashi, Mohammad Mahdavi & Tahmineh Akbarzadeh
To cite this article: Ghasem Rezanejade Bardajee, Aseyeh Ghaedi, Shohreh Hekmat, Ghazale
Abarashi, Mohammad Mahdavi & Tahmineh Akbarzadeh (2017): A green and efficient synthesis
of 2-thioxoquinazolinone derivatives in water using potassium thiocyanate, Journal of Sulfur
Chemistry, DOI: 10.1080/17415993.2017.1325891
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Date: 18 May 2017, At: 01:38

JOURNAL OF SULFUR CHEMISTRY, 2017
https://doi.org/10.1080/17415993.2017.1325891
A green and efficient synthesis of 2-thioxoquinazolinone
derivatives in water using potassium thiocyanate
Ghasem Rezanejade Bardajeea, Aseyeh Ghaedia, Shohreh Hekmata, Ghazale
Abarashia, Mohammad Mahdavib and Tahmineh Akbarzadehc,d
aDepartment of Chemistry, Payame Noor University (PNU), Tehran, Iran; bEndocrinology and Metabolism
Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical
Sciences, Tehran, Iran; cDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of
Medical Sciences, Tehran, Iran; dDrug Design & Development Research Center, Tehran University of Medical
Sciences, Tehran, Iran
ABSTRACT
ARTICLE HISTORY
Received 15 January 2017
Accepted 27 April 2017
Green chemistry is one of the most important routes for the syn-
thesis of heterocyclic compounds. In this regard, the synthesis of
2-thioxoquinazolinone derivatives was achieved by condensation of
versatile materials including isatoic anhydride, amine and potassium
thiocyanate in the green medium of water. This convenient and effi-
cient method affords the desired products with good to excellent
yields.
KEYWORDS
Thioxoquinazolinone; green
chemistry; water; isatoic
anhydride; potassium
thiocyanate
O
O
R1
R1
1) H2O,rt
R2NH2
O
NR2
S
2) KSCN, trace AcOH
N
H
O
N
H
1
2
3
4
H2O, 100 °C
1. Introduction
Providing greener chemical processes and synthetic approaches has become one of the aims
of research during the past decade in efforts designed to produce chemical compounds
[1–3]. In this regard, new procedures were designed by chemists to reduce environmental
pollution and to save energy [4]. Optimizing the reaction conditions in the presence of
environmental friendly solvents (e.g. water and ethanol) instead of toxic solvents is desir-
able for green synthesis of organic compounds especially heterocycles [5]. Quinazolinone
derivatives are classified as N-rich fused heterocycles which have widespread biological
activities [6], including anti-inflammatory [7], anti-parkinsonism [8], anticonvulsant [9],
CONTACT Ghasem Rezanejade Bardajee
rezanejad@pnu.ac.ir, ghrezanejad@yahoo.com
Department of
Chemistry, Payame Noor University (PNU), PO BOX 19395-3697, Tehran, Iran; Tahmineh Akbarzadeh
akbarzad@tums.ac.ir
Sciences, Tehran, Iran
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical
© 2017 Informa UK Limited, trading as Taylor & Francis Group

2
G. REZANEJADE BARDAJEE ET AL.
O
O
O
O
N
N
O2N
N
F
N
S
N
H
S
N
H
Altanserin
Nitroaltanserin
Figure 1. Chemical structures of altanserin and nitroaltanserin.
antimicrobial [10], anticancer and analgesic properties [11]. The 2-thioxoquinazolinone
framework is also a favorable unit in drug design since many commercial pharmaceuticals
contain this structure [12] such as Altanserin and Nitroaltanserin (Figure 1) as 5-HT2A
receptor antagonist drugs [13].
2-Thioxoquinazolinone derivatives have been produced using different methodolo-
gies; however low yields, hazardous chemicals and harsh reaction conditions are some
of their drawbacks. For example, CS2 or isothiocyanates were used in these reactions
and are flammable, high toxic, stinky and noxious. Despite the mentioned disadvan-
tages, some reported procedures have opened new prospects for the synthesis of 2-
thioxoquinazolinones [14–23]. For instance, one-pot three-component reactions of isatoic
anhydride, amines and carbon disulfide were accomplished in ethanol with potassium
hydroxide under reflux and microwave irradiation conditions [24]. Additionally, 2-
thioxoquinazolinones were obtained by the use of isothiocyanates in DMSO/H2O in the
absence of any catalyst under microwave irradiation [24, 25]. Hence, in this article, a more
efficient, greener and rapid way for the synthesis of 2-thioxoquinazolinone derivatives is
described. According to our previous syntheses based on isatoic anhydride and amines
[25–31], we have designed the current synthesis using isatoic anhydrides, amines and
potassium thiocyanate in acetic acid and water to give 2-thioxoquinazolinones in high
yields within shorter reaction times.
2. Results and discussion
Primarily, we designed a new one-pot process for the synthesis of 2-thioxoquinazolinone
derivatives under mild and green conditions. The synthetic procedure was performed
through the reaction of isatoic anhydride 1 (1 mmol), potassium thiocyanate (1 mmol) and
amine 2a (1 mmol) in various solvents including EtOH, MeOH, CH2Cl2 and H2O under
Table 1. Investigation on various conditions for synthesis of 4a–4o.
Entry
Solvent
Acid
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
9
EtOH
MeOH
H2O
AcOH
AcOH
AcOH
–
HCl
HCl
HCl
HCl
HCl
12
10
3
15
10
10
12
13
10
30
25
85
trace
15
15
10
20
trace
H2O
CH2Cl2
EtOH
MeOH
H2O
CH2Cl2
aIsolated yield.

JOURNAL OF SULFUR CHEMISTRY
3
Table 2. Synthesis of 2-thioxoquinazolinone derivatives 4 (Scheme 1).
O
O
R1
R1
1) H2O, rt
R2NH2
O
NR2
2) KSCN, trace AcOH
3
N
H
O
N
H
S
2
4
1
H2O, 100 ºC
Entry
1
R1
R2 NH2
Product 4
Yield (%)a
80
H
4a
NH2
NH2
2a
2
3
H
H
4b
4c
85
58
O
2b
NH2
NH2
N
2c
MeO
4
5
H
H
4d
4e
75
75
2d
OMe
NH2
2e
MeO
6
Cl
4f
78
MeO
NH2
2f
MeO
MeO
7
8
H
H
4g
4h
83
85
NH2
2g
NH2
2h
MeO
MeO
9
H
H
4i
4j
77
78
NH2
2i
10
NH2
NH2
2j
Cl
11
H
4k
85
2k
(continued)

4
G. REZANEJADE BARDAJEE ET AL.
Table 2. Continued.
Entry
12
R1
R2 NH2
Product 4
Yield (%)a
84
H
H
4l
Cl
NH2
2l
13
14
4m
74
NH2
2m
NH2
H
H
4n
4o
70
68
2n
15
NH2
2o
aIsolated yield.
O
O
N
R1
R1
1) H2O,rt
NR2
S
R2NH2
O
2) KSCN, trace AcOH
3
N
H
O
2
4
H
1
H2O, 100 ºC
R1: H, Cl
R2:
ArCH2_ , Ph_ , Furan CH2_
CH3(CH2)2_ , PyridineCH2_
CHv(CH2)3_ , (CH3)2CH_
Yield:68-85%
Scheme 1. General outline for the synthesis of 2-thioxoquinazolinones (4a–4o).
different conditions. Also, the impact of different acidic catalysts was studied on this reac-
tion and the best results were obtained in acetic acid (AcOH), which is a safe, green and
available organic acid. To prevent side reactions of amine with KSCN 3, it should be added
to the mixture after completion of the reaction between isatoic anhydride and the amine.
However, the results showed that the use of acid catalyst is important to successfully obtain
the product 4a (Table 1, Entries 3 and 4). In addition, water was selected as the best solvent
for this reaction (Table 1, Entry 3). By applying the optimized conditions (Table 1, Entry
3), a series of 2-thioxoquinazolinone derivatives 4 were obtained using different kinds of
amines (Table 2). Initially, a mixture of isatoic anhydride 1 and amine 2 was stirred in
H2O at room temperature. Then potassium thiocyanate was added to the mixture and the
reaction was continued in H2O at 80°C in the presence of acetic acid (Scheme 1).
To investigate generality of this procedure, various primary aliphatic and aromatic
amines were applied in this reaction and a range of 2-thioxoquinazolinone derivatives
(4a–4o) were obtained in 68–85% yields (Table 2). Generally, benzylamine derivatives
bearing both electron-donating and electron-withdrawing groups on the aromatic ring
gave the corresponding products in high yields (Table 2, Entries 4–12). Furthermore, ani-
line, primary and secondary alkyl amines produced the desired products in good yields
(Table 2, Entries 13–15). A plausible reaction mechanism for the formation of product
4 is proposed in Scheme 2. According to the chemistry of isatoic anhydride [32–36],

JOURNAL OF SULFUR CHEMISTRY
5
O
O
O
3
R1
R1
R1
KSC
NHR2
NH2
N
O
NHR2
S
- CO2
R2NH2
+
AcOH
N
H
O
NH
H
1
2
5
6
N
O
O
H
R1
H+
R1
NR2
NR2
-NH3
NH
NH2
N
H
S
7
4
S
Scheme 2. The proposed mechanism for the formation of 2-thioxoquinazolinone 4.
nucleophilic addition of amine 2 to the carbonyl group of isatoic anhydride 1, resulted
in the removal of a carbon dioxide molecule and formation of anthranilamide 5. Then,
nucleophilic attack of amino group of intermediate 5 on KSCN achieved intermediate
6. In the final step, intermediate 7 is obtained and after elimination of NH3 following
an intramolecular cyclization, the corresponding compound 4 is obtained. Characteri-
zation of the products was achieved by their physical and spectral data. Although there
are several methods for the synthesis of the entitled heterocycles, due to the importance
of introducing green methods for the preparation of heterocycles in organic synthesis,
the present methodology can be regarded as a versatile strategy for the synthesis of 2-
thioxoquinazolinone derivatives. The advantages of using water as the solvent in organic
reactions include simplifying of the work-up procedure, the improvement of selectivity
and reactivity, and moderate reaction conditions. Moreover, unusual reactivity and reverse
selectivity can happen in the presence of water in comparison with organic solvents during
synthesis of organic compounds. In the present study, acetic acid and potassium thio-
cyanate are highly soluble in water while they have low solubility in methanol or ethanol
solvents. Moreover, the ring opening reaction of isatoic anhydride in aqueous medium is
a highly desirable reaction. For these reasons, applying water as the reaction medium is
the best condition for this methodology. Herein, we report an efficient and environmen-
tally benign method for the preparation of 2-thioxoquinazolinone derivatives 4 in high
yields. This method can be considered as an interesting alternative to other complex and
multi-step procedures reported in the literature. The present method is simple with no need
of tedious work-up procedures. It is an appropriate replacement for previous approaches
reported for the synthesis of the mentioned products. Considering the fact that most 2-
thioxoquinazolinone derivatives show interesting biological activities, the new compounds
synthesized in this paper are valuable for further pharmaceutical research.
3. Conclusion
In conclusion, we have reported a rapid, efficient and environmentally benign method
for the preparation of 2-thioxoquinazolinones via the ring opening reaction of isatoic
anhydrides, amines and potassium thiocyanate using acetic acid in aqueous medium.

6
G. REZANEJADE BARDAJEE ET AL.
The advantages of the present method are the eco-friendly approach and simple work-
up procedure that make this method applicable for medical researchers to make progress
during their drug discovery investigations based on thioxoquinazolinones.
4. Experimental
Merck and Sigma Aldrich chemicals were used in this protocol with no further purification.
1
Melting points were measured on a Kofler hot-stage device. H and 13C NMR spectra
were taken on a Bruker FT-500 instrument, using tetramethylsilane as an internal stan-
dard. Infrared (IR) spectra were recorded on a Nicolet Magna FTIR550 spectrophotometer
using KBr plate. Mass spectra were obtained on an Agilent Technology (HP) mass spec-
trometer with an ionization potential of 70 eV. Elemental analysis was accomplished with
an Elementar Analysen system GmbH VarioEL CHNS.
5. General procedure for the preparation of 2-thioxoquinazolinone
derivatives 4a–4o
A mixture of isatoic anhydride 1 (1 mmol) and the corresponding amine 2 (1 mmol)
in H2O (5 mL) was stirred for 1 h at ambient temperature. Then, KSCN (1 mmol) in
acetic acid (1 mL) and H2O (5 mL) was added to the mixture and the reaction was
continued for 3 h at 80°C. After completion of the reaction, the crude product was fil-
tered, washed well with water and recrystallized in hot water to gain the pure colorless
product 4.
5.1. 3-benzyl-2,3-dihydro-2-thioxoquinazolin-4(1H)-one (4a).
White crystals; yield: 214 mg (80%), mp 247–249°C ([18] lit. 248°C).
5.2. 3-((furan-2-yl) methyl)-2,3-dihydro-2-thioxoquinazolin-4(1H)-one (4b).
White crystals; yield: 219 mg (85%), mp 233–234°C; IR (KBr): 3346, 3034, 1658, 1625,
1
1523, 1498 cm−1; HNMR (500 MHz, DMSO-d6): 5.65(s, 2H, NCH2), 6.34(dd, J = 3.2,
0.7 Hz, 1H, furan), 6.37 (dd, J = 3.2, 1.8 Hz, 1H, furan), 7.34 (t, J = 7.5 Hz, 1H, Ar, 7.39
(d, J = 7.5 Hz, 1H, Ar), 7.53–7.54 (m, 1H, furan), 7.73 (td, J = 7.5, 1.3 Hz, 1H, Ar), 7.97
(dd, J = 7.5, 1.3 Hz, 1H, Ar), 13.03 (s, 1H, NH);13C NMR (125 MHz, DMSO-d6): 42.2,
108.3, 110.5, 115.3, 115.7, 124.6, 127.3, 135.7, 136, 139.0, 142.0, 159.0, 175.0. Mass m/z
(%): 258 [M+] (2), 167 (41), 149 (53), 113 (21), 104 (14), 91 (19), 83 (27), 69 (94), 43 (100).
Anal. Calcd for C13H10N2O2S: C, 60.45; H, 3.90; N, 10.85%. Found: C, 60.65; H, 4.15; N,
10.66.
5.3. 2,3-Dihydro-3- (pyridin-2-yl)methyl-2-thioxoquinazolin-4(1H)-one (4c).
White crystals; yield: 156 mg (58%), mp 265–268°C; IR (KBr): 3278, 3071, 1684, 1613, 1596
1532, 1481 cm−1, 1HNMR (500 MHz, DMSO-d6): 5.70 (s, 2H, NCH2), 7.22 (t, J = 7.5 Hz,
ꢀ
ꢀ
1H, H6), 7.27 (d, J = 7.2 Hz, 1H, H2 ), 7.36 (t, J = 7.2 Hz, 1H,H5 ), 7.45 (d, J = 7.2 Hz,
ꢀ
1H, H8), 7.70 (t, J = 7.2 Hz, 1H, H4 ), 7.75 (t, J = 7.5 Hz, 1H, H7), 7.96 (d, J = 7.5 Hz,

JOURNAL OF SULFUR CHEMISTRY
7
13
ꢀ
1H, H5), 8.40 (t, J = 7.2 Hz, 1H, H3 ), 13.04 (s, 1H, NH); C NMR (125 MHz, DMSO-d6):
50.0, 115.4, 115.7, 120.7, 121.9, 124.5, 127.4, 135.6, 136.5, 139.2, 148.8, 155.0, 159.0, 175.6.
Mass m/z (%): 269 [M+] (7), 263 (11), 236 (100), 225 (23), 189 (15), 183 (25), 170 (16), 162
(54), 149 (98), 118 (32), 109 (61), 97 (15), 71 (46), 57 (92); Anal. Calcd for C14H11N3OS:
C, 62.43; H, 4.12; N, 15.60%. Found: C, 62.70; H, 4.25; N, 15.75.
5.4. 2,3-Dihydro-3-(4-methoxybenzyl)-2-thioxoquinazolin-4(1H)-one (4d).
White crystals; yield: 223 mg (75%), mp 233–235°C; IR (KBr): 3260, 3080, 1655, 1615, 1590,
1525, 1470 cm−1, 1HNMR (500 MHz, DMSO-d6): 3.71 (s, 3H, OCH3), 5.77 (s, 2H, NCH2),
ꢀ
ꢀ
ꢀ
ꢀ
6.8 (d, J = 6.7 Hz, 2H, H3 , H5 ), 7.3–7.3 (m, 3H, H6, H2 , H6 ), 7.4 (d, J = 8.0 Hz, 1H, H8),
7.70 (t, J = 8.0 Hz, 1H, H7), 7.94 (d, J = 8.0 Hz, 1H, H5), 13.05 (s, 1H, NH); 13CNMR
(125 MHz, DMSO-d6): 48.0, 55. 1, 113.5, 115.4, 115.7, 124.8, 127.3, 128.9, 129.0, 135.6,
139.0, 158.3, 159.3, 175.3. Anal. Calcd for C16H14N2O2S: C, 64.41; H, 4.73; N, 9.39. Found:
C, 64.01; H, 4.33; N, 8.99.
5.5. 2,3-Dihydro-3-(2-methoxyphenethyl)-2-thioxoquinazolin 4(1H)-one (4e).
White crystals; yield: 234 mg(75%), mp 202–205°C, IR (KBr): 3265, 3081, 1669, 1620, 1580,
1550, 1491 cm−1, 1HNMR (500 MHz, DMSO-d6): 2.9 (t, J = 7.8 Hz, 2H, NCH2CH2), 3.63
ꢀ
(s, 3H, OCH3), 4.63 (t, J = 7.8 Hz, 2H, NCH2CH2), 6.87 (t, J = 7.5 Hz, 1H, H3 ), 6.93 (d,
ꢀ
ꢀ
ꢀ
J = 7.5 Hz, 1H, H6 ), 7.17–7.22 (m, 2H, H4 , H5 ), 7.33 (dt, J = 7.8 Hz, 1H, H6), 7.39 (d,
J = 7.8 Hz, 1H, H8), 7.78 (td, J = 7.8, 1.2 Hz, 1H, H7), 7.95 (dd, J = 7.8, 1.2 Hz, 1H, H5),
12.92 (s, 1H, NH); 13CNMR (125 MHz, DMSO-d6): 26.8, 45.4, 55.2, 110.0, 115.5, 120.3,
124.4, 126.5, 127.2, 127.8, 129.8, 135.4, 136.2, 139.0, 157.4, 159.1. m/z (%) = 312.09 (45,
M+), 257 (11), 229 (20), 178 (24), 134 (100), 111 (25), 91 (40), 69 (98). Anal. Calcd for
C17H16N2O2S: C, 65.36; H, 5.16; N, 8.97. Found: C, 64.96; H, 4.96; N, 8.57.
5.6. 6-Chloro-3-(3,4-dimethoxyphenethyl)-2,3-dihydro-2-thioxoquinazolin-4(1H)-
one(4f).
White crystals; yield: 293 mg (78%), mp 245–248°C; IR (KBr): 3280, 3091, 1669, 1645, 1580,
1
1528, 1470 cm−1. HNMR (500 MHz, DMSO-d6): 2.90 (t, J = 8.1 Hz, 2H, NCH2CH2),
3.73 (s, 3H, OCH3), 3.75 (s, 3H, OCH3), 4.50 (t, J = 8.1 Hz, 2H, NCH2CH2), 6.80 (dd,
ꢀ
ꢀ
ꢀ
J = 8.1, 1.9 Hz, 1H, H6 ), 6.86 (d, J = 1.9 Hz, 1H, H2 ), 6.89 (d, J = 8.1 Hz, 1H, H5 ), 7.40
(d, J = 8.8 Hz, 1H, H8), 7.80(dd, J = 8.8, 2.4 Hz, 1H, H7), 7.89 (d, J = 2.4 Hz, 1H, H5),
13.15 (s, 1H, NH). 13CNMR (125 MHz, DMSO-d6): 31.7, 47.2, 55.3, 55.5, 112.0, 112.3,
116.9, 117.9, 120.4, 126.1, 128.3, 130.8, 135.4, 137.9, 147.5, 148.7, 158.2, 174. Anal. Calcd
for C18H17ClN2O3S: C, 57.37; H, 4.55; N, 7.43. Found: C, 56.97; H, 4.15; N, 7.03.
5.7. 3-(3,4-Dimethoxyphenethyl)-2,3-dihydro-2-thioxoquinazolin-4(1H)-one (4 g)
[26].
White crystals; yield: 283 mg (83%), mp 230–232°C; IR (KBr): 3180, 3040, 1686, 1622, 1589,
1541 cm−1. 1HNMR (500 MHz, DMSO-d6): 2.91 (t, J = 8.0 Hz, 2H, NCH2CH2), 3.73 (s,
3H, OCH3), 3.74 (s, 3H, OCH3), 4.58 (t, J = 8.0 Hz, 2H, NCH2CH2), 6.80 (d, J = 8.5 Hz,

8
G. REZANEJADE BARDAJEE ET AL.
ꢀ
ꢀ
ꢀ
1H, H5 ), 6.87–6.90 (m, 2H, H2 , H6 ), 7.34 (t, J = 8.0 Hz, 1H, H6), 7.40 (d, J = 8.0 Hz, 1H,
H8), 7.74 (t, J = 8.0 Hz, 1H, H7), 7.96 (d, J = 8.0 Hz, 1H, H5), 12.96 (s, 1H, NH). 13CNMR
(125 MHz, DMSO-d6): 31.8, 47.1, 55.3, 55.5, 112.0, 112.3, 115.5, 115.6, 120.5, 124.5, 127.2,
130.9, 135.4, 139.0, 147.5, 148.7, 159.1, 174.9. Anal. Calcd for C18H18N2O3S: C, 63.14; H,
5.30; N, 8.18. Found: C, 62.74; H, 4.90; N, 7.78.
5.8. 2,3-Dihydro-3-phenyl-2-thioxoquinazolin-4(1H)-one (4 h)
White crystals; yield: 156 mg (58%), mp 234–235°C ([18] > 260°C); IR (KBr): 3247, 3031,
1664, 1622, 1530, 1488 cm−1. 1HNMR (500 MHz, DMSO-d6|): 7.27–7.28 (m, 2H, ArH),
7.35 (t, J = 7.7 Hz, 1H, H6), 7.40–7.49 (m, 4H, ArH), 7.79 (td, J = 7.7, 1.0 Hz, 1H, H7),
7.96 (dd, J = 8.0, 1.0 Hz, 1H, H5), 13.03 (s, 1H, NH). 13CNMR (125 MHz, DMSO-d6):
115.6, 116.1, 124.3, 127.4, 128.0, 128.8, 128.9, 135.5, 139.3, 139.6, 159.7.176.0. MS (70 eV):
m/z (%) = 254.05 (5, M+), 167 (53), 149 (84), 113 (17), 104 (16), 91 (10), 83 (38), 69 (70),
57 (100), 43 (98). Anal. Calcd for C14H10N2OS: C, 66.12; H, 3.96; N, 11.02. Found: C, 65.72;
H, 3.56; N, 10.62.
5.9. 3-(3,4-Dimethoxyphenyl)-2,3-dihydro-2-thioquinazolin-4(1H)-one (4i) [19].
White crystals; yield: 241 mg (77%), mp 245–248°C; IR (KBr): 3180, 3030, 1696, 1648, 1623,
1537, 1488 cm−1. 1HNMR (500 MHz, DMSO-d6): 3.71 (s, 3H, OCH3), 3.82 (s, 3H, OCH3),
ꢀ
ꢀ
6.80 (dd, J = 8.5, 2.3 Hz, 1H, H6 ), 6.93 (d, J = 2.3 Hz, 1H, H2 ), 7.02 (d, J = 8.5 Hz,
1H, H5ꢀ), 7.34 (t, J = 7.8 Hz, 1H, H6), 7.44 (d, J = 7.8 Hz, 1H, H8), 7.78 (td, J = 7.8,
1.2 Hz, 1H, H7), 7.95 (dd, J = 7.8, 1.2 Hz, 1H, H5), 13.00 (s, 1H, NH). 13CNMR (125 MHz,
DMSO-d6): 55.5, 55.6, 111.4, 112.7, 115.6, 116.1, 121.0, 124.2, 127.4, 132.0, 135.5, 139.5,
148.4, 148.9, 159.8, 176.4. MS (70 eV): m/z (%) = 314.07 (100, M+), 297 (27), 268 (16), 240
(14), 180(10), 162(74), 145(43), 111(23), 83(41), 57(41). Anal. Calcd for C16H14N2O3S: C,
61.99; H, 5.20; N, 8.50. Found: C, 61.59; H, 4.60; N, 8.40.
5.10. 2,3-(Dihydro-3-(1-phenylethyl)-2-thioxoquinozolin-4(1H)-one (4j) [19].
White crystals; yield: 219 mg (78%), mp 237–239°C; IR (KBr): 3310, 3045, 1656, 1633,
1
1526, 1499 cm−1. HNMR (500 MHz, DMSO-d6): 1.86 (d, J = 6.5 Hz, 3H, CH3), 7.20
(q, J = 6.5 Hz, 1H, CH), 7.28–7.34 (m, 6H, ArH), 7.42 (d, J = 7.5 Hz, 1H, H8), 7.72 (t,
J = 7.5 Hz, 1H, H7), 7.99 (d, J = 7.5 Hz, 1H, H5), 13.06 (s, 1H, NH). 13CNMR (125 MHz,
DMSO-d6): 14.9, 56.6, 115.6, 116.4, 124.5, 125.6, 126.4, 127.0, 128.0, 135.4, 138.9, 140.3,
158.3, 176.5. Anal. Calcd for C16H14N2OS: C, 68.06; H, 5.00; N, 9.92. Found: C, 67.66; H,
4.60; N, 9.32.
5.11. 3-(2-Chlorobenzyl)-2,3-dihydro-2-thioxoquinazolin-4(1H)-one (4k).
White crystals; yield: 256 mg (85%), mp 231–233°C ([18] 262°C); IR (KBr): 3182, 3043,
1
1680, 1630, 1560, 1498 cm−1. HNMR (500 MHz, DMSO-d6): 5.88 (s, 2H, NCH2), 6.97
ꢀ
ꢀ
ꢀ
(d, J = 7.5 Hz, 1H, H6 ), 7.13–7.17 (m, 2H, H3 , H4 ), 7.20 (t, J = 7.7 Hz, 1H, H6), 7.36
ꢀ
(t, J = 7.5 Hz, 1H, H5 ), 7.43 (d, J = 7.7 Hz, 1H, H8), 7.70 (t, J = 7.7 Hz, 1H, H7), 8.17
(d, J = 7.7 Hz, 1H, H5), 10.12 (s, 1H, NH). 13CNMR (125 MHz, DMSO-d6): 48.0, 114.4,

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125.2, 125.9, 126.7, 128.2, 128.9, 129.7, 131.1, 132.9, 135.0, 135.8, 138.3, 159.5, 176.2. Anal.
Calcd for C15H11ClN2OS: C, 59.50; H, 3.66; N, 9.25. Found: C, 59.10; H, 3.26; N, 8.85.
5.12. 3-(4-Chlorobenzyl)-2,3-dihydro-2-thioxoquinazolin-4(1H)-one (4 l).
White crystals; yield: 253 mg (84%), mp 227–229°C ([18] 230°C).
5.13. 2,3-Dihydro-3-propyl-2-thioxoquinazolin-4(1H)-one (4 m).
White crystals; yield: 162 mg (74%), mp 175–178°C ([35] 191°C); IR (KBr): 3190, 3052,
1699, 1648, 1596, 1435, 1501 cm−1. 1HNMR (500 MHz, DMSO-d6): 1.04 (t, J = 7.5 Hz,
3H, CH3CH2CH2N), 1.86 (sextet, J = 7.5 Hz, 2H, CH3CH2CH2N), 4.50 (t, J = 7.5 Hz,
2H, CH3CH2CH2N), 7.23 (d, J = 7.7 Hz, 1H, H8), 7.34 (t, J = 7.5 Hz, 1H, H6), 7.67 (td,
J = 7.7, 1.3 Hz, 1H, H7), 8.15 (dd, J = 7.7, 1.3 Hz, 1H, H5), 10.90 (s, 1H, NH). 13CNMR
(125 MHz, DMSO-d6): 11.2, 20.1, 48.4, 114.5, 116.2, 125.0, 128.5, 135.3, 138.4, 159.6, 175.7.
Anal. Calcd for C11H12N2OS: C, 59.97; H, 5.49; N, 12.72. Found: C, 59.57; H, 5.09; N, 12.32.
5.14. 2,3-Dihydro-3-isopropyl-2-thioxoquinazolin-4(1H)-one (4n).
White crystals; yield: 154 mg (70%), mp 202–204°C ([37,38]177–179°C); IR (KBr): 3191,
3055, 1690, 1628, 1625, 1535, 1480 cm−1 1HNMR (500 MHz, DMSO-d6): 1.04 (d,
.
J = 7.0 Hz, 6H, (CH3)2CHN), 6.06 (q, J = 7.0 Hz, 1H, (CH3)2CHN), 7.32 (t, J = 8.0 Hz,
1H, H6), 7.34 (d, J = 8.0 Hz, 1H, H8), 7.67 (t, d, J = 8.0, 1.3 Hz, 1H, H7), 8.15 (dd, J = 8.0,
1.3 Hz, 1H, H5), 12.87 (s, 1H, NH). 13CNMR (125 MHz, DMSO-d6): 18.5, 52.5, 115.3,
116.7, 124.4, 126.9, 135.2, 138.8, 159.4, 175.2. Anal. Calcd for C11H12N2OS: C, 59.97; H,
5.49; N, 12.72. Found: C, 59.57; H, 5.09; N, 12.32.
5.15. 3-Butyl-2,3-dihydro-2-thioxoquinazolin-4(1H)-one (4o).
1
White crystals; yield: 159 mg (68%), mp 183–185°C ([34,35,39]175–176°C). [40] H
NMR (500 MHz, DMSO-d6): d 0.94 (t, 3H, J = 6.8 Hz), 1.31–1.42(m, 2H), 1.63–1.72 (m,
2H), 4.40 (t, 2H, J = 6.8 Hz), 7.18–7.20 (m, 2H) 7.74 (t, 1H, J = 6.8 Hz), 7.96 (d, 1H,
J = 6.8 Hz), 12.90 (brs, 1H,NH). MS (70 eV): m/z (%) = 234 [M+] (12), 177 (41), 77 (53),
43 (100). Anal. Calcd for C12H14N2OS: C, 61.51; H, 6.02; N, 11.96. Found: C, 61.11; H,
4.62; N, 11.56.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by grants from PNU, INSF and Tehran University of Medical Sciences as
research project [Grant No: 33150-33-03-95].
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