Convenient and sequential one-pot route for synthesis of 2-thioxoquinazolinone and quinazolinobenzothiazinedione derivatives

Article abstract of DOI:10.1007/s00706-013-1110-8

A new and efficient synthetic process has been developed for preparation of 2-thioxoquinazolinone and quinazolinobenzothiazinedione derivatives. The related products were synthesized through reaction of isatoic anhydride, amines/anthranilic acids, and carbon disulfide (CS₂) in the presence of potassium hydroxide in ethanol at reflux. Graphical abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-013-1110-8

Monatsh Chem (2014) 145:497–504
DOI 10.1007/s00706-013-1110-8
ORIGINAL PAPER
Convenient and sequential one-pot route for synthesis
of 2-thioxoquinazolinone and quinazolinobenzothiazinedione
derivatives
•
Mehdi Asadi Shiva Masoomi Seyed Mostafa Ebrahimi
•
•
•
•
•
Mohammad Mahdavi Mina Saeedi Abbas Shafiee
Alireza Foroumadi
Received: 20 May 2013 / Accepted: 21 October 2013 / Published online: 26 November 2013
Ó Springer-Verlag Wien 2013
Abstract A new and efficient synthetic process has been
developed for preparation of 2-thioxoquinazolinone and
quinazolinobenzothiazinedione derivatives. The related
products were synthesized through reaction of isatoic
anhydride, amines/anthranilic acids, and carbon disulfide
(CS2) in the presence of potassium hydroxide in ethanol at
reflux.
fungicides [6–9]. Altanserin and nitroaltanserin (Fig. 1)
belong to this class of heterocycles and are utilized as
5-HT2A receptor antagonist drugs [10].
While literature survey reports various procedures for the
synthesis of 2-thioxoquinazolinones [1, 5, 11–18], synthesis
of quinazolinobenzothiazinedione and their properties have
been discussed rarely [19]. In view of the fact that 2-thi-
oxoquinazolinones and quinazolinobenzothiazinediones
can possess important biological activities, their signifi-
cance attracted our attention. In continuation of our efforts
towards synthesis of heterocycles [20–22] and especially
promising biologically active compounds [23, 24], we
present herein a new, efficient, and easy work-up procedure
for synthesis of 2-thioxoquinazolinones 4 and quinazoli-
nobenzothiazinedione 6 via sequential one-pot three-
component reaction of isatoic anhydride 1, amines 2 or
anthranilic acids 5, and carbon disulfide (3) in the pre-
sence of potassium hydroxide in ethanol at reflux
(Schemes 1, 2).
Keywords 2-Thioxoquinazolinones ꢀ
Quinazolinobenzothiazinedione ꢀ Isatoic anhydride ꢀ
Anthranilic acids
Introduction
Quinazolinone derivatives have attracted extensive interest
owing to their biological activities [1–4]. Fused quinaz-
olinone derivatives such as 2-thioxoquinazolinones
comprise a large group of biologically active and medici-
nally important compounds. They have displayed
remarkable antiinflammatory and analgesic activity [5] and
have also been used as plant growth regulators and
Results and discussion
Focusing on designing a new one-pot multicomponent
reaction in the absence of expensive catalysts and microwave
irradiation for synthesis of 2-thioxoquinazolinones, isatoic
anhydride attracted our attention as an available starting
material [25–28]. In this research, not only an efficient and
facile protocol for the synthesis of 2-thioxoquinazolinone
explained, but synthesis of quinazolinobenzothiazinediones
is disclosed (Schemes 1, 2).
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-013-1110-8) contains supplementary
material, which is available to authorized users.
M. Asadi
School of Chemistry, University College of Science, University
of Tehran, PO Box 14155-6455, Tehran, Iran
S. Masoomi ꢀ S. M. Ebrahimi ꢀ M. Mahdavi ꢀ M. Saeedi ꢀ
A. Shafiee ꢀ A. Foroumadi (&)
Our synthetic process started with investigation of
reaction between isatoic anhydride 1 (1 mmol), benzyl-
amine (2a, 1 mmol), and carbon disulfide (1 mmol) in a
variety of different solvents, e.g., EtOH, MeOH, CH2Cl2,
Department of Medicinal Chemistry, Faculty of Pharmacy and
Pharmaceutical Sciences Research Center, Tehran University of
Medicinal Sciences, Tehran, Iran
e-mail: aforoumadi@yahoo.com
123

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M. Asadi et al.
Fig. 1 Altanserin and
nitroaltanserin
Scheme 1
Scheme 2
should be added after complete reaction of isatoic anhy-
dride and amine. Using the optimized condition, a series of
reactions using different kinds of amines were performed
Table 1 Investigation of various conditions for synthesis of 4a
Entry
Solvent
Base
Yield/%a
1
2
3
4
5
6
7
8
EtOH
KOH
KOH
KOH
KOH
NaOH
NaOH
NEt3
85
40
5
to synthesize 2-thioxoquinazolinone derivatives
(Table 1).
4
MeOH
CH2Cl2
PhCH3
EtOH
During our investigation, we took anthranilic acid
derivatives 5 in the above three-component reaction and
directly accessed quinazolinobenzothiazinedione deriva-
tives 6 (Scheme 2). It was found that they could be
synthesized under the same optimized conditions in good
yield. The results are summarized in Table 3.
10
25
10
20
0
MeOH
EtOH
EtOH
K2CO3
Although we have not established the mechanism of
reactions in an experimental manner, a possible explanation
is proposed in Scheme 3. On the basis of the established
chemistry of isatoic anhydride [29–31], it involves the
addition of primary amine 2 to isatoic anhydride 1, resulting
in the formation of anthranilamide 7. Then, in the presence of
base, the intermediate 8 is easily obtained by nucleophilic
attack of nitrogen to CS2. Cyclization reaction (formation of
9) followed by elimination of H2S affords the corresponding
compounds 4. In the case of preparation of quinazolino-
benzothiazinedione 6, the same mechanism is assumed, and
in the last step, nucleophilic attack of S (C=S, thiocarbonyl
group) at carbonyl group of carboxylic acid leads to the
formation of products 6 (Scheme 4).
The reaction times were the same as the optimized conditions
a
Isolated yield
and toluene, under various conditions. Some results are
presented in Table 1. Our results revealed that use of a
strong base is essential to obtain the corresponding product
4a (Table 2, entry 1). It was found that carrying out the
reaction in ethanol at reflux offers the best conditions.
Also, the influence of different bases was studied, and the
results showed that the best performance was obtained with
potassium hydroxide (KOH). Hence, KOH was selected as
an optimum, available, and inexpensive base. To prevent
complications due to possible reaction of amine and CS2, it
123

2-Thioxoquinazolinone and quinazolinobenzothiazinedione derivatives
499
Table 2 Synthesis of 2-thioxoquinazolinone derivatives 4 (Scheme 1)
Entry
R1
R2-NH2
Product 4
M.p./°C
Yield/%a
Observed
Reported
248 [13]
1
H
4a
247–248
85
NH2
NH2
NH2
2
3
H
H
4b
4c
233–234
265–268
–
–
90
85
O
N
4
5
H
H
4d
4e
233–235
202–205
–
–
79
75
NH2
MeO
OMe
NH2
6
7
8
Cl
H
4f
245–248
230–232
234–235
–
75
85
75
MeO
MeO
NH2
4g
4h
–
MeO
MeO
NH2
H
[260 [13]
NH2
9
H
4i
245–247
–
77
NH2
OMe
OMe
10
11
H
H
4j
237–239
231–233
–
80
80
NH2
4k
262 [17]
Cl
NH2
13
H
4l
227–229
230 [17]
85
NH2
Cl
123

500
M. Asadi et al.
Yield/%a
Table 2 continued
Entry
R1
R2-NH2
Product 4
M.p./°C
Observed
Reported
191 [32]
14
15
H
H
4m
4n
175–178
202–204
80
80
NH2
177.5–178.5 [33]
175–176 [34]
NH2
16
H
4o
183–185
78
NH2
a
Isolated yield
derivatives via sequential one-pot reaction of isatoic
anhydride, amines/anthranilic acids, and carbon disulfide.
Short reaction time, good product yield, use of simple
starting materials, and absence of complex and expensive
catalysis and microwave irradiation are the key advantages
of this method. The simplicity of the present procedure
makes it an interesting alternative to complex, multistep
approaches. This protocol does not need tedious workup to
isolate the products and can emerge as a novel replacement
for previous procedures for the synthesis of the mentioned
compounds.
Table 3 Synthesis of quinazolinobenzothiazinedione derivatives 6
(Scheme 2)
Entry R1 Anthranilic acid Product M.p./°C
Yield/
a
%
5
6
Observed Reported
1
2
3
4
5
a
H
H
H
H
Cl
6a
299–300 300 [19] 85
CO2H
NH2
6b
6c
6d
6e
[300
306 [19] 85
Cl
CO2H
NH2
298–300 296 [19] 80
Experimental
Me
CO2H
NH2
All chemicals were purchased from Merck and Sigma-
Aldrich and used without further purification. Melting
1
[300
[300
–
–
80
75
MeO
MeO
CO2H
NH2
points were taken on a Kofler hot-stage apparatus. H and
13C NMR spectra were recorded on a Bruker FT-500, using
tetramethylsilane (TMS) as internal standard. Infrared (IR)
spectra were obtained on a Nicolet Magna FTIR 550
spectrophotometer (in KBr). Mass spectra were determined
on an Agilent Technology (HP) mass spectrometer oper-
ating at ionization potential of 70 eV. Elemental analysis
was performed with an Elementar Analysensystem GmbH
VarioEL CHNS mode.
CO2H
NH2
Isolated yield
General procedure for synthesis of 2-thioxoquinazolinones
All products were characterized by their spectra and phys-
ical data. 1H nuclear magnetic resonance (NMR) and 13CNMR
spectra of all synthesized compounds associated with this
article can be found in the Electronic Supplementary Material.
4 and quinazolinobenzothiazinediones 6
A solution of isatoic anhydride 1 (1 mmol) and appro-
priate amine 2 or 5 (1 mmol) in 10 cm3 EtOH was stirred
at reflux for 3 h. Then, a mixture of carbon disulfide
(2 mmol) and KOH (1 mmol) was added to the reaction
mixture and stirring continued under the same conditions
for 3 h. The reaction mixture was cooled to room tem-
perature and poured into 20 cm3 water. The precipitate
Conclusions
We have developed a novel protocol for the synthesis of
2-thioxoquinazolinone and quinazolinobenzothiazinedione
123

2-Thioxoquinazolinone and quinazolinobenzothiazinedione derivatives
501
Scheme 3
Scheme 4
2,3-Dihydro-3-[(pyridin-2-yl)methyl]-2-thioxoquinazolin-
was collected by filtration, washed with water, and re-
crystallized using EtOH to give 4 or 6 as colorless
crystals.
4(1H)-one (4c, C14H11N3OS)
White crystals; m.p.: 265–268 °C; 1H NMR (500 MHz,
DMSO-d6): d = 5.77 (s, 2H, NCH2), 7.22 (t, J = 7.5 Hz,
0
1H, H6), 7.27 (d, J = 7.2 Hz, 1H, H3 ), 7.36 (t, J = 7.2 Hz,
3-Benzyl-2,3-dihydro-2-thioxoquinazolin-4(1H)-one
(4a, C15H12N2OS)
0
1H, H5 ), 7.45 (d, J = 7.2 Hz, 1H, H8), 7.71 (t, J = 7.2 Hz,
0
1H, H4 ), 7.78 (t, J = 7.5 Hz, 1H, H7), 7.96 (d, J = 7.5 Hz,
White crystals; m.p.: 247–248 °C ([13] 248 °C).
0
1H, H5), 8.41 (t, J = 7.2 Hz, 1H, H3 ), 13.04 (s, 1H,
NH) ppm; 13C NMR (125 MHz, DMSO-d6): d = 50.0,
115.4, 115.7, 120.7, 121.9, 124.5, 127.4, 135.6, 136.5, 139.2,
3-[(Furan-2-yl)methyl]-2,3-dihydro-2-thioxoquinazolin-
4(1H)-one (4b, C13H10N2O2S)
ꢀ
148.8, 155.4, 159.4, 175.6 ppm; IR (KBr): m = 3,268, 3,071,
White crystals; m.p.: 233–234 °C; 1H NMR (500 MHz,
DMSO-d6): d = 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, H6), 7.39 (d, J = 7.5 Hz, 1H,
H8), 7.53–7.54 (m, 1H, furan), 7.73 (td, J = 7.5, 1.3 Hz,
1H, H7), 7.97 (dd, J = 7.5, 1.3 Hz, 1H, H5), 13.03 (s,
1H, NH) ppm; 13C NMR (125 MHz, DMSO-d6):
d = 42.2, 108.3, 110.5, 115.3, 115.7, 124.6, 127.3,
135.7, 136.0, 139.0, 142.0, 159.0, 175.0 ppm; IR
1,664, 1,623, 1,596, 1,532, 1,481 cm-1; MS (70 eV):
m/z (%) = 269.06 (7, M?), 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).
2,3-Dihydro-3-(4-methoxybenzyl)-2-thioxoquinazolin-
4(1H)-one (4d, C16H14N2O2S)
White crystals; m.p.: 233–235 °C; 1H NMR (500 MHz,
DMSO-d6): d = 3.71 (s, 3H, OCH3), 5.77 (s, 2H, NCH2),
0 0
6.85 (d, J = 6.7 Hz, 2H, H3 , H5 ), 7.33–7.36 (m, 3H, H6,
ꢀ
(KBr): m = 3,246, 3,044, 1,658, 1,621, 1,533,
1,488 cm-1; MS (70 eV): m/z (%) = 257.05 (2, [M-
1]?), 167 (41), 149 (53), 113 (21), 104 (14), 91 (19), 83
(27), 69 (94), 43 (100).
H2 , H6 ), 7.42 (d, J = 8.0 Hz, 1H, H8), 7.76 (t,
J = 8.0 Hz, 1H, H7), 7.96 (d, J = 8.0 Hz, 1H, H5), 13.05
(s, 1H, NH) ppm; 13C NMR (125 MHz, DMSO-d6):
0
0
123

502
M. Asadi et al.
d = 48.0, 55.0, 113.5, 115.4, 115.7, 124.6, 127.3, 128.6,
129.0, 135.6, 139.1, 158.3, 159.3, 175.4 ppm; IR (KBr):
2,3-Dihydro-3-phenyl-2-thioxoquinazolin-4(1H)-one
(4h, C14H10N2OS)
m = 3,250, 3,070, 1,665, 1,625, 1,590, 1,535, 1,480 cm
.
White crystals; m.p.: 234–235 °C ([13] [260 °C); 1H
NMR (500 MHz, DMSO-d6): d = 7.27–7.28 (m, 2H,
ArH), 7.35 (t, J = 7.7 Hz, 1H, H6), 7.40–7.49 (m, 4H,
H8, 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) ppm; 13C
NMR (125 MHz, DMSO-d6): d = 115.6, 116.1, 124.3,
127.4, 128.0, 128.8, 128.9, 135.5, 139.3, 139.6, 159.7,
-1
ꢀ
2,3-Dihydro-3-(2-methoxyphenethyl)-2-thioxoquinazolin-
4(1H)-one (4e, C17H16N2O2S)
White crystals; m.p.: 202–205 °C; 1H NMR (500 MHz,
DMSO-d6): d = 2.98 (t, J = 7.8 Hz, 2H, NCH2CH2), 3.73
(s, 3H, OCH3), 4.63 (t, J = 7.8 Hz, 2H, NCH2CH2), 6.87
ꢀ
176.0 ppm; IR (KBr): m = 3,247, 3,031, 1,664, 1,622,
0
(t, J = 7.5 Hz, 1H, H3 ), 6.93 (d, J = 7.5 Hz, 1H, H6 ),
0
1,530, 1,488 cm-1; 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).
0
0
7.17–7.22 (m, 2H, H4 , H5 ), 7.33 (td, J = 7.8, 1.2 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) ppm; 13C NMR (125 MHz, DMSO-d6):
d = 26.8, 45.4, 55.2, 110.7, 115.5, 120.3, 124.4, 126.5,
127.2, 127.8, 129.8, 135.4, 136.2, 139.0, 157.4, 159.1,
3-(3,4-Dimethoxyphenyl)-2,3-dihydro-2-thioxoquinazolin-
4(1H)-one (4i, C16H14N2O3S)
White crystals; m.p.: 245–248 °C; 1H NMR (500 MHz,
DMSO-d6): d = 3.71 (s, 3H, OCH3), 3.82 (s, 3H, OCH3),
ꢀ
175.0 ppm; IR (KBr): m = 3,265, 3,080, 1,667, 1,629,
1,593, 1,530, 1,481 cm-1; MS (70 eV): m/z (%) = 312.09
(45, M?), 257 (11), 229 (20), 178 (24), 134 (100), 111 (25),
91 (40), 69 (98).
0
6.80 (dd, J = 8.5, 2.3 Hz, 1H, H6 ), 6.93 (d, J = 2.3 Hz,
0
0
1H, H2 ), 7.02 (d, J = 8.5 Hz, 1H, H5 ), 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) ppm; 13C NMR (125 MHz,
DMSO-d6): d = 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,
6-Chloro-3-(3,4-dimethoxyphenethyl)-2,3-dihydro-2-thioxo-
quinazolin-4(1H)-one (4f, C18H17ClN2O3S)
White crystals; m.p.: 245–248 °C; 1H NMR (500 MHz,
DMSO-d6): d = 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,
ꢀ
159.8, 176.4 ppm; IR (KBr): m = 3,180, 3,030, 1,696,
1,648, 1,623, 1,537, 1,488 cm-1
;
MS (70 eV):
m/z (%) = 314.07 (100, M?), 297 (27), 268 (16), 240 (14),
0
2H, NCH2CH2), 6.80 (dd, J = 8.1, 1.9 Hz, 1H, H6 ), 6.86
180 (10), 162 (74), 145 (43), 111 (23), 83 (41), 57 (41).
0
0
(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)
ppm; 13C NMR (125 MHz, DMSO-d6): d = 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, 174.8 ppm; IR
2,3-Dihydro-3-(1-phenylethyl)-2-thioxoquinazolin-4(1H)-
one (4j, C16H14N2OS)
White crystals; m.p.: 237–239 °C; 1H NMR (500 MHz,
DMSO-d6): d = 1.86 (d, J = 6.5 Hz, 3H, CH3), 7.20 (q,
J = 6.5 Hz, 1H, CH), 7.28–7.34 (m, 6H, H6, 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) ppm; 13C NMR
(125 MHz, DMSO-d6): d = 14.9, 56.6, 115.6, 116.4,
124.5, 125.6, 126.4, 127.0, 128.0, 135.4, 138.9, 140.3,
ꢀ
(KBr): m = 3,260, 3,081, 1,669, 1,625, 1,591, 1,528,
1,479 cm-1
.
3-(3,4-Dimethoxyphenethyl)-2,3-dihydro-2-
thioxoquinazolin-4(1H)-one (4g, C18H18N2O3S)
ꢀ
158.3, 176.5 ppm; IR (KBr): m = 3,310, 3,025, 1,666,
White crystals; m.p.: 230–232 °C; 1H NMR (500 MHz,
DMSO-d6): d = 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,
1,623, 1,526, 1,492 cm-1; MS (70 eV): m/z (%) = 282.08
(56, M?), 178 (100), 149 (55), 134 (11), 120 (34), 104 (57),
77 (45), 57 (27).
0
2H, NCH2CH2), 6.80 (d, J = 8.5 Hz, 1H, H5 ), 6.87–6.90
0
0
(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) ppm; 13C NMR
(125 MHz, DMSO-d6): d = 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 ppm; IR (KBr):
3-(2-Chlorobenzyl)-2,3-dihydro-2-thioxoquinazolin-4(1H)-
one (4k, C15H11ClN2OS)
1
White crystals; m.p.: 231–233 °C ([17] 262 °C); H NMR
(500 MHz, CDCl3): d = 5.88 (s, 2H, NCH2), 6.97 (d,
0
J = 7.5 Hz, 1H, H6 ), 7.13–7.17 (m, 2H, H3 , H4 ), 7.20 (t,
0
0
0
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) ppm; 13C NMR
(125 MHz, CDCl3): d = 48.0, 114.4, 125.2, 125.9, 126.8,
128.2, 128.9, 129.7, 131.1, 132.9, 135.0, 135.8, 138.3,
m = 3,180, 3,040, 1,686, 1,622, 1,589, 1,541,
1,484 cm-1; MS (70 eV): m/z (%) = 342.10 (3, M?),
282 (67), 167 (82), 149 (100), 120 (25), 104 (41), 71 (31),
57 (41).
123

2-Thioxoquinazolinone and quinazolinobenzothiazinedione derivatives
503
159.5, 176.2 ppm; IR (KBr): mꢀ = 3,182, 3,033, 1,690,
3-Methyl-5H,12H-quinazolino[3,2-a][3,1]benzothiazine-
1,620, 1,540, 1,488 cm-1
.
5,12-dione (6c, C16H10N2O2S)
White crystals; m.p.: 298–300 °C ([19] 296 °C).
3-(4-Chlorobenzyl)-2,3-dihydro-2-thioxoquinazolin-4(1H)-
one (4l, C15H11ClN2OS)
2,3-Dimethoxy-5H,12H-quinazolino[3,2-a][3,1]benzothi-
azine-5,12-dione (6d, C17H12N2O4S)
White crystals; m.p.: [300 °C; 1H NMR (500 MHz,
DMSO-d6): d = 3.73 (s, 3H, OCH3), 3.82 (s, 3H, OCH3),
6.74 (s, 1H, H1), 7.27 (t, J = 7.5 Hz, 1H, H9), 7.41 (d,
J = 7.5 Hz, 1H, H8), 7.64 (s, 1H, H4), 7.71 (t, J = 7.5 Hz,
1H, H10), 7.90 (d, J = 7.5 Hz, 1H, H11) ppm; 13C NMR
(125 MHz, DMSO-d6): d = 55.4, 55.7, 112.9, 114.2,
114.9, 115.5, 116.5, 121.7, 123.6, 127.3, 132.4, 134.9,
White crystals; m.p.: 227–229 °C ([17] 230 °C).
2,3-Dihydro-3-propyl-2-thioxoquinazolin-4(1H)-one
(4m, C11H12N2OS)
1
White crystals; m.p.: 175–178 °C ([28] 191 °C); H NMR
(500 MHz, CDCl3): d = 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) ppm; 13C NMR
(125 MHz, CDCl3): d = 11.2, 20.1, 48.4, 114.6, 116.2,
147.2, 149.7, 160.0, 167.6, 176.4 ppm; IR (KBr):
-1
ꢀ
m = 3,040, 2,928, 2,830, 1,680, 1,670, 1,640, 1,560 cm
.
10-Chloro-5H,12H-quinazolino[3,2-a][3,1]benzothiazine-
5,12-dione (6e, C15H7ClN2O2S)
White crystals; m.p.: [300 °C; 1H NMR (500 MHz,
CDCl3): d = 6.89–7.31 (m, 5H, ArH), 7.77–7.84 (m, 2H,
ArH) ppm; 13C NMR (125 MHz, CDCl3): d = 116.0,
118.8, 119.2, 123.6, 127.3, 128.7, 129.5, 130.2, 131.2,
133.0, 134.3, 135.3, 136.5, 160.4, 175.9 ppm.
125.0, 128.5, 135.3, 138.4, 159.6, 175.7 ppm; IR (KBr):
-1
ꢀ
m = 3,190, 3,052, 1,699, 1,648, 1,626, 1,535, 1,481 cm
.
2,3-Dihydro-3-isopropyl-2-thioxoquinazolin-4(1H)-one
(4n, C11H12N2OS)
White crystals; m.p.: 202–204 °C ([29] 177.5–178.5 °C);
1H NMR (500 MHz, DMSO-d6): d = 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 (td, J = 8.0, 1.3 Hz, 1H, H7), 8.15 (dd, J = 8.0,
1.3 Hz, 1H, H5), 12.87 (s, 1H, NH) ppm; 13C NMR
(125 MHz, DMSO-d6): d = 18.5, 52.5, 115.3, 116.7,
Acknowledgments We gratefully acknowledge the partial financial
support from Tehran University of Medicinal Sciences Research
Council and Iran National Science Foundation (INSF).
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124.4, 126.9, 135.2, 138.8, 159.4, 175.2 ppm; IR (KBr):
-1
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