A Metal- and Ligand-Free Synthesis of Quinazolin-4(3H)-ones via a Bu4NI/TBHP-Mediated Oxidative Cleavage of the Olefinic C=C Bond

Article abstract of DOI:10.1134/S1070428020080163

Abstract: A metal and ligand-free protocol has been developed for the synthesis of quinazolin-4(3H)-ones in moderate to good yields from o-aminobenzamide and alkenes via a Bu₄NI/TBHP-mediated oxidative cleavage of the C=C bond in alkenes.

Full text of DOI:10.1134/S1070428020080163

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 8, pp. 1446–1454. © Pleiades Publishing, Ltd., 2020.
A Metal- and Ligand-Free Synthesis of Quinazolin-4(3H)-ones
via a Bu4NI/TBHP-Mediated Oxidative Cleavage
of the Olefinic C=C Bond
B. K. Karasalaa, P. Gollamudia, B. Inkollua, and S. Vidavalura,*
a Department of Organic Chemistry and FDW, Andhra University, Visakhapatnam, 530003 India
*e-mail: sidduchem@gmail.com
Received February 25, 2020; revised March 01, 2020; accepted March 15, 2020
Abstract—A metal and ligand-free protocol has been developed for the synthesis of quinazolin-4(3H)-ones in
moderate to good yields from o-aminobenzamide and alkenes via a Bu4NI/TBHP-mediated oxidative cleavage of
the C=C bond in alkenes.
Keywords: 2-substituted quinazolin-4(3H)-ones, o-aminobenzamide, alkene, tetrabutylammonium iodide, tetra-
butyl hydroperoxide
DOI: 10.1134/S1070428020080163
INTRODUCTION
Due to their valuable biological and pharmacological
properties, myriad strategies have been developed for
the synthesis of quinazolinones [22–26]. Among the
reported strategies, condensation of 2-aminobenzamide
with aldehydes followed by oxidation of an aminal
intermediate is the most explored strategy [24,
27–29]. However, most known synthetic approaches
are associated with high consumption of oxidants,
ligands, and expensive catalysts.
Quinazolinone is a privileged structural motif in
many natural products and approximately 200 naturally
occurring quinazolinone alkaloids [1–5]. Natural and
unnatural derivatives of quinazolinones exhibit a wide
range of biological activities, including hypnotic,
sedative, analgesic, anticonvulsant, antitussive, anti-
bacterial, antidiabetic, anti-inflammatory, and antitumor
[4, 6–18]. Furthermore, quinazolinones have played
a pivotal role in drug discovery, and a number of
quinazolinone-based drugs, for example, Ispinesib,
Afloqualone, Diproqualone, Methaqualone, etc. [4,
19–21], are in the market (Scheme 1).
On the other hand, transition metal or metal-free
oxidative cleavage of the C=C bond has received
significant attention in organic synthesis, because it
provides in situ oxygen-containing functional groups,
such as ketone and aldehyde carbonyls, for constructing
Scheme 1.
O
N
NH2
O
N
O
N
O
N
H2N
N
N
OH
N
N
CH3
OH
N
F
O
Ispinesib
(kinase inhibitor)
Afloqualone
(muscle-relaxant)
Methaqualone
(anticancer)
Diproqualone
(sedative-hypnotic)
1446

A METAL- AND LIGAND-FREE SYNTHESIS OF QUINAZOLIN-4(3H)-ONES
1447
Scheme 2.
O
O
Bu4NI/TBHP
80°C, 8 h
NH2
NH2
+
NH
R
N
R
1a
2a–2o
3a–3o
complex molecules from inexpensive olefinic feedstock
[30]. There are only a few examples in the literature
of the synthesis of quinazolinones from alkenes. For
example, Wei Liu et al. [31] prepared quinazolinones
via palladium-catalyzed oxidative cleavage of alkenes.
Very recently Pan and co-workers [32] have reported the
electrochemical synthesis of quinazolinone derivatives
from o-aminobenzamides and alkenes with an RVC
(reticulated vitreous carbon) anode and a platinum plate
cathode. Bharate and co-workers [33] have synthesized
quinazolinone and their derivatives via the condensation
of o-aminobenzamide with arylalkynes (or styrenes) in
presenceofmolecularoxygenasanoxidant.However,the
above-mentioned methods suffered of such drawbacks
as the use of expensive catalysts and ligands and toxic
solvents, as well as low yields. Therefore, to develop
metal- and ligand-free strategies for the synthesis of
quinazolinones from alkenes remains quite a relevant
task. Recently, a Bu4NI/TBHP oxidation system has
emerged as a powerful tool in organic synthesis [34].
In continuation our work [35–36] on the development
of new methods of synthesis of heterocyclic compounds
with the use of the Bu4NI/TBHP-oxidation system,
we report here a metal- and ligand-free synthesis of
quinazolinones from alkenes via the TBHP/Bu4NI-
mediated oxidative cleavage of the olefinic C=C bond
(Scheme 2).
(Table 1, entries 5–8). Various solvents, such as PhCN,
CH3CN, EtOAc, DMSO, and THF, were also tested,
but no improvement in yields was obtained (Table 1,
entries 9–13). Then we focused on the quantity of the
catalyst and oxidant: when the quantities of catalyst
and oxidant were increased to 8 equiv and 15 mol % or
decreased to 4 equiv and 5 mol %, respectively, lower
yields of 2-phenylquinazolinone 3a were obtained
(Table 1, entries 14–17). Moreover, the reaction did
not occur in the absence of either catalyst or oxidant
(Table 1, entries 18 and 19).
With the optimized conditions in hand, we
investigated the scope of the oxidative cleavage of the
C=C bond in arylalkenes for the synthesis of quinazolin-
4(3H)-ones, and the results are shown in Table 2. The
electrically neutral styrene (2a) reacted very smoothly
and gave the corresponding product 3a in 89% yield
(Table 2, entry 1). Styrenes with both electron-donor
and electron- acceptor groups readily reacted with
o-aminobenzamide and provided desired quinazolinones
3b–3m in moderate to good yields. With styrenes
2b–2f, which have electron-donor groups on the aryl
ring, specifically p-methyl, p-methoxy, m-methyl,
m-methoxy, and o-methyl, gave corresponding
quinazolinones 3b–3f in good yields. Similarly, styrenes
2g–2m with electron-acceptor groups, specifically F, Cl,
Br, and NO2, reacted smoothly with 1 and generated
desired quinazolinones 3g–3m in moderate yields. At
the same time, o-substituted styrenes gave lower yields
compared to p-substituted styrenes (cf. yields 66 and
67% for 3j–3k vs 78 and 76% for 3g–3h, respectively),
implying some steric effect on this transformation.
Heteroaryl-substituted alkenes 2n and 2o, too, reacted
efficiently, and corresponding products 3n and 3o
were obtained in satisfactory yields (64 and 70%,
respectively).
RESULTS AND DISCUSSION
Our investigation started with the reaction between
o-aminobenzamide (1) and alkene 2a in the presence of
10 mol % of KI and 6 equiv of TBHP (70% in water)
at 80°C to obtain 2-phenylquinazolinone 3a in 61%
yield (Table 1, entry 1). Other catalysts, including
Bu4NCl, Bu4NBr, and Bu4NI, were also tested (Table 1,
entries 2–4). The results demonstrated that Bu4NI
was the best choice: the yield of compound 3a with
this catalyst was 89% (Table 1, entry 4). Further we
screened a number of oxidants instead of TBHP with
the aim to improve the reaction performance; however,
the other oxidants were inferior for this transformation
To gain insight into the reaction mechanism,
a series of control experiments were carried out.
Benzaldehyde (A) could be generated from styrene
(2a) via oxidation under the optimized conditions
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1448
KARASALA et al.
Table 1. Optimization of the reaction conditionsa
Entry no.
Catalyst, mol %
Oxidant, equiv
Solvent
Yield of 3a, %
1
2
KI (10)
TBHP (6)
TBHP (6)
TBHP (6)
TBHP (6)
K2S2O8 (6)
DTBP (6)
H2O2 (6)
–
61
Bu4NCl (10)
Bu4NBr (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (10)
Bu4NI (15)
Bu4NI (5)
–
Not detected
3
–
Not detected
4
–
89
5
–
0
6
–
0
7
–
31
8
m-CBPA (6)
TBHP (6)
TBHP (6)
TBHP (6)
TBHP (6)
TBHP (6)
TBHP (8)
TBHP (4)
TBHP (6)
TBHP (6)
–
PhCN
CH3CN
EtOAc
DMSO
THF
–
0
9
16
10
11
12b
13
14
15
16
17
48
12
76
Not detected
78
60
75
70
–
–
–
18
19
–
TBHP
–
–
–
Not detected
Not detected
Bu4NI (10)
a Reaction conditions: o-aminobenzamide (1) (1.5 mmol, 0.20 g), styrene (2a) (1.91 mmol, 0.19 g), 80°C, 8 h.
b Reaction temperature 110°C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 8 2020

A METAL- AND LIGAND-FREE SYNTHESIS OF QUINAZOLIN-4(3H)-ONES
Table 2. Synthesis of 2-substitited-quinazolin-4(3H)-ones 3a–3oa
1449
Entry no.
R
Alkene
Product
Yield, %
1
2
Ph
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
89
86
85
82
83
80
78
76
73
66
67
68
70
64
70
p-MeC6H4
p-OMeC6H4
m-MeC6H4
m-OMeC6H4
o-MeC6H4
p-FC6H4
3
4
5
6
7
2g
2h
2i
3g
3h
3i
8
p-ClC6H4
9
p-BrC6H4
o-FC6H4
10
11
12
13
14
15
2j
3j
o-ClC6H4
2k
2l
3k
3l
m-BrC6H4
p-NO2C6H4
Pyridin-4-yl
Furan-2-yl
2m
2n
2o
3m
3n
3o
a Reaction conditions: o-aminobenzamide (1) (1.5 mmol, 0.20 g ), alkene 2 (1.91 mmol, 0.19 g), Bu4NI (10 mol %), TBHP (6 equiv).
[Scheme 3, reaction (1)]. The reaction of aldehyde A
with o-aminobenzamide (1) gave product 3a in a yield
of 89% [Scheme 3, reaction (2)]. Whenever a radical
quencher, like 2,2,6,6-tetramethylpyridine N-oxide
(TEMPO) or butylated hydroxyl toulene (BHT), was
added to the reaction mixture, the formation of product
3a was completely suppressed [Scheme 3, reaction (3)].
This result showed that the studied transformation may
involve a radical mechanism.
Based on these above experimental results and earlier
reports [37], we can propose a plausible mechanism of
the transformation (Scheme 4). Presumably, the reaction
starts with the formation of aldehyde A via the oxidative
cleavage of the C=C bond in the alkene in the presence
of Bu4NI/TBHP. Then aldehyde A condenses with
o-aminobenzamide (1) to form an imine intermediate
B. Finally, the latter undergo cyclization followed by
oxidative elimination of HI to form quinazolin-4(3H)-
one 3a.
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KARASALA et al.
Scheme 3.
H
O
Bu4NI/TBHP
80°C, 8 h
(1)
(2)
2a
A, 91%
O
N
O
O
NH
Bu4NI/TBHP
80°C, 8 h
NH2
NH2
+
H
1
3a, 89%
A
O
O
NH
Bu4NI/TBHP
(3)
NH2
+
80°C, 8 h
N
TEMPO
or
NH2
BHT
1
2a
3a, trace
In conclusion, we have developed a simple and
efficient method for the synthesis of quinazolin-4(3H)-
ones via Bu4NI/TBHP-mediated oxidative cleavage of
the C=C bond in alkenes under metal- and ligand-free
conditions. Alkenes with various substitutions smoothly
reacted with o-aminobenzamide to afford the target
products in moderate-to-good yields. The developed
protocol provides a simple and green synthetic approach
to quinazolin-4(3H)-ones, which avoids usage of toxic
and expensive catalysts and ligands.
EXPERIMENTAL
All chemicals were purchased from Sigma Aldrich
andAVRASynthesis Private Limited Company and used
as received without special purification unless stated
otherwise. Reactions were monitored by TLC on Silica
Scheme 4.
1/2 I2
t-BuOOH
t-BuO
OH
I
O
H
O
Bu4NI
TBHP
NH2
1
N
2a
A
B
Bu4NI/TBHP cyclization
HI
O
O
NH
N
NH
Oxidation
H
N
HI
I
3a
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A METAL- AND LIGAND-FREE SYNTHESIS OF QUINAZOLIN-4(3H)-ONES
1451
gel 60 F254 in ethyl acetate–hexane (3 : 7 v/v), the spots
were visualized under UV light (254 nm). The products
were purified by column chromatography on silica gel
(100–200 mesh). The melting points were determined
in an open capillary tube and are not corrected. The 1H
and 13C NMR spectra were recorded on a 400 MHz
spectrometer using TMS as internal standard; the
chemical shifts are reported in δ (ppm) relative to
internal TMS. The mass spectra were recorded on an
Agilent 1100 LC/MSD instrument.
NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 3.88 s
(3H, OCH3), 7.07 d (2Harom, J 6.4 Hz), 7.47 t (1Harom
,
J 8.0 Hz), 7.65 d (1Harom, J 9.6 Hz), 7.80 t (1Harom, J
8.8 Hz), 8.12 d (1Harom, J 9.6 Hz), 8.17 d (2Harom, J
7.6 Hz), 12.34 br.s (1H, NH). 13C NMR spectrum
(100 MHz, DMSO-d6), δ, ppm: 56.3, 115.6, 121.4, 124.8,
125.7, 126.0, 127.1, 129.6, 136.0, 149.3, 153.2, 162.5,
163.4. Mass spectrum (LC-HRMS), m/z: 253.0941
[M + H]+. C15H12N2O2. M 253.0932.
2-(m-Tolyl)quinazolin-4(3H)-one (3d). White solid,
mp 221–222°C (221–223°C [22]).1H NMR spectrum
(400 MHz, DMSO-d6), δ, ppm: 2.41 s (3H, CH3), 7.36–
7.48 m (2Harom), 7.48–7.57 m (1Harom), 7.71 d (1Harom, J
7.6 Hz), 7.76–7.85 m (1Harom), 7.98 d (1Harom, J 8.0 Hz),
8.17 d (1Harom, J 8.0, 1.0 Hz), 8.06 s (1Harom), 12.53 br.s
(1H, NH). 13C NMR spectrum (100 MHz, DMSO-d6),
δ, ppm: 20.6, 120.4, 124.8, 125.6, 126.7, 127.2, 128.2,
129.0, 131.8, 132.7, 135.0, 137.7, 149.3, 152.4, 162.6.
Mass spectrum (LC-HRMS), m/z: 237.0995 [M + H]+.
C15H12N2O. M 237.0983.
Synthesis of quinazolin-4(3H)-ones 3a–3o (general
procedure). o-Aminobenzamide (1) (1.5 mmol), styrene
2a–2o (1.91 mmol), Bu4NI (10 mol %), and TBHP
(6 equiv) were loaded into an oven dried RB flask with
a stir bar, and the mixture was stirred on an oil both
at 80°C for 8 h. After completion of the reaction (by
TLC), the reaction mixture was extracted with water
and ethyl acetate. The organic phase was dried over
anhydrous Na2SO4, and the solvent was removed under
a vacuum. The crude product was purified by column
chromatography (ethyl acetate: hexane) to obtain
corresponding pure product 3a–3o in 64–89% yield.
2-(m-Methoxyphenyl)quinazolin-4(3H)-one (3e).
1
White solid, mp 180–182°C (181–183°C [22]). H
The physicochemical and spectral characteristics
of the synthesized compounds are consistent with
published data.
NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 3.86 s
(3H, OCH3), 7.15–7.18 d.d (1Harom, J 7.2 Hz), 7.47 t
(1Harom, J 7.2 Hz), 7.54 t (1Harom, J 8.0 Hz), 7.75 d
(2Harom, J 8.0 Hz), 7.81 d (1Harom, J 7.6 Hz), 7.81–7.85 m
(1Harom), 8.18 d (1Harom, J 7.2 Hz), 12.55 br.s (1H, NH).
13C NMR spectrum (100 MHz, DMSO-d6), δ, ppm:
20.1, 121.9, 126.0, 126.6, 127.2, 127.7, 129.4, 130.1,
130.6, 134.3, 134.7, 136.2, 149.5, 154.4, 163.1. Mass
spectrum (LC-HRMS), m/z: 253.0942 [M + H]+.
C15H12N2O2. M 253.0932.
2-Phenylquinazolin-4(3H)-one (3a). White solid,
1
mp 234–236°C (232–235°C [22]). H NMR spectrum
(400 MHz, DMSO-d6), δ, ppm: 7.45 t (1Harom, J
8.4 Hz), 7.52–7.56 m (3Harom), 7.77–7.86 m (2Harom),
8.14 d (2Harom, J 8.0 Hz), 8.37 d (1Harom, J 8.0 Hz),
12.16 br.s (1H, NH). 13C NMR spectrum (100 MHz,
DMSO-d6), δ, ppm: 120.0, 126.3, 126.8, 127.5, 128.5,
130.0, 131.7, 132.8, 136.7, 149.3, 152.5, 163.0. Mass
spectrum (LC-HRMS), m/z: 223.0835 [M + H]+.
C14H10N2O. M 223.0827.
2-(o-Tolyl)quinazolin-4(3H)-one (3f). White solid,
mp 216–219°C (216–218°C [26]).1H NMR spectrum
(400 MHz, DMSO-d6), δ, ppm: 2.36 s (3H, CH3), 7.16–
7.19 m (2Harom), 7.27–7.31 m (1Harom), 7.6 d.d (2Harom
,
2-(p-Tolyl)quinazolin-4(3H)-one (3b). White solid,
mp 240–242°C (239–242°C [24]). H NMR spectrum
(400 MHz, CDCl3), δ, ppm: 2.44 s (3H, CH3), 7.33 d
(2Harom, J 8.0 Hz),7.46 t (1Harom, J 8.0 Hz), 7.77–
1
J 2.4, 8.8 Hz), 7.82 d (1Harom, J 9.2 Hz), 7.93–7.99 m
(1Harom), 8.24 d (1Harom, J 8.0 Hz), 12.43 br.s (1H, NH).
13C NMR spectrum (100 MHz, DMSO-d6), δ, ppm: 20.0,
121.3, 124.5, 126.0, 126.5, 127.4, 129.4, 130.2, 131.3,
134.9, 135.3, 136.2, 148.3, 153.7, 161.4. Mass spectrum
(LC-HRMS), m/z: 237.0988 [M + H]+. C15H12N2O.
M 237.0983.
7.81 m (2Harom), 8.04 d (2Harom, J 8.4 Hz), 8.29 d (1Harom
,
J 8.0 Hz), 12.53 br.s (1H, NH). 13C NMR spectrum
(100 MHz, CDCl3), δ, ppm: 22.6, 121.7, 126.5, 126.9,
127.8, 128.0, 129.8, 130.0, 136.2, 141.9, 149.9, 152.8,
162.7. Mass spectrum (LC-HRMS), m/z: 237.0997
[M + H]+. C15H12N2O. M 237.0983.
2-(p-Fluorophenyl)quinazolin-4(3H)-one
White solid, mp 284–286°C (284–287°C [26]). 1H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 7.40 t (2Harom
J 7.6 Hz), 7.55–7.57 m (1Harom), 7.75 d (1Harom, J
(3g).
,
2-(p-Methoxyphenyl)quinazolin-4(3H)-one (3c).
1
White solid, mp 246–247°C (247–249°C [24]). H
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 8 2020

1452
KARASALA et al.
8.0 Hz),7.85–7.88 m (1H, NH), 8.16 d.d (1Harom, J 2.4,
7.2 Hz), 8.24–8.28 m (2Harom), 12.51 br.s (1H, NH). 13C
NMR spectrum (100 MHz, DMSO-d6), δ, ppm: 115.6 d
(JCF 21.9 Hz), 121.2, 125.8, 127.3, 127.7, 129.2 d (JCF
2.9 Hz), 130.3 d (JCF 9.0 Hz), 134.7, 148.3, 150.8, 162.6,
164.1 d (JCF 249.5 Hz). Mass spectrum (LC-HRMS),
m/z: 241.0726 [M + H]+. C14H9FN2O. M 241.0732.
127.4, 127.7, 129.3, 130.7, 131.1, 131.4, 133.9, 134.7,
148.6, 152.6, 161.7. Mass spectrum (LC-HRMS), m/z:
258.0427 [M + H]+. C14H9ClN2O. M 258.0374.
2-(m-Bromophenyl)quinazolin-4(3H)-one
(3l).
1
White solid, mp 293–295°C (294–296°C [33]). H
NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 7.54 d.d
(2Harom, J 2.4, 8.0 Hz), 7.76 t (2Harom, J 8.0 Hz),
7.84 t (1Harom, J 8.0 Hz), 8.16 t (2Harom, J 12.0 Hz),
8.36 br.s (1Harom), 12.62 s (1H, NH). 13C NMR spec-
trum (100 MHz, DMSO-d6), δ, ppm: 121.3, 123.5,
125.7, 126.9, 127.2, 128.6, 130.5, 132.4, 134.3,
135.0, 135.8, 149.2, 151.7, 162.2. Mass spectrum
(LC-HRMS), m/z: 301.9880 [M + 2]+. C14H9BrN2O. M
301.9878.
2-(p-Chlorophenyl)quinazolin-4(3H)-one
(3h).
1
White solid, mp 298–299°C (298–300°C [24]). H
NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 7.53 t
(1Harom, J 7.6 Hz), 7.65 d (2Harom, J 8.0 Hz), 7.77 t
(1Harom, J 8.0 Hz), 7.85 t (1Harom, J 7.6 Hz), 8.16 d
(1Harom, J 8.8 Hz), 8.23 d (2Harom, J 8.8 Hz), 12.51 br.s
(1H, NH). 13C NMR spectrum (100 MHz, DMSO-d6),
δ, ppm: 122.5, 125.5, 126.1, 127.8, 128.4, 131.1, 132.4,
134.2, 136.4, 149.2, 153.6, 161.8. Mass spectrum
(LC-HRMS), m/z: 258.0458 [M + H]+. C14H9ClN2O. M
258.0374.
2-(p-Nitrophenyl)quinazolin-4(3H)-one
Yellow solid, mp > 300°C (> 300°C [33]). H NMR
(3m).
1
spectrum (400 MHz, DMSO-d6), δ, ppm: 7.62 t (1Harom
J 7.6 Hz), 7.82 d (1Harom, J 7.6 Hz), 7.91 t (1Harom
,
,
2-(p-Bromophenyl)quinazolin-4(3H)-one
(3i).
J 7.6 Hz), 8.20 d (1Harom, J 8.0 Hz), 8.38–8.44 m
(4Harom), 12.84 s (1H, NH). 13C NMR spectrum
(100 MHz, DMSO-d6), δ, ppm: 162.6, 151.1, 149.5,
148.8, 139.1, 136.3, 135.3, 129.8, 129.2, 127.9, 126.4,
124.1. Mass spectrum (LC-HRMS), m/z: 268.0681
[M + H]+. C14H9N3O3. M 2684.0677.
1
White solid, mp 293–295°C (292–295°C [24]). H
NMR spectrum (400 MHz, DMSO-d6), δ, ppm:
7.33 t (1Harom, J 5.6 Hz), 7.62–7.66 m (3Harom), 7.86 t
(1Harom, J 8.4 Hz), 8.18–8.24 m (3Harom), 12.36 br.s
(1H, NH). 13C NMR spectrum (100 MHz, DMSO-d6),
δ, ppm: 122.3, 125.5, 126.6, 127.2, 128.8, 131.3, 132.4,
132.9, 136.3, 149.6, 152.8, 162.4. Mass spectrum
(LC-HRMS), m/z: 301.9925 [M + 2]+. C14H9BrN2O. M
301.9878.
2-(Pyridin-4-yl)quinazolin-4(3H)-one (3n). White
solid, mp 281–284°C (282–284°C [33]). 1H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 7.52–7.61 m
(2Harom), 7.76 d (1Harom, J 8.0 Hz), 7.88 t (1Harom, J
7.6 Hz), 8.23 d (1Harom, J 8.0 Hz), 8.54 d (1H, Py-H, J
8.0 Hz), 8.78 d (1H, Py-H, J 8.0 Hz), 9.32 s (1H, Py-H),
12.76 br.s (1H, NH). 13C NMR spectrum (100 MHz,
DMSO-d6), δ, ppm: 121.6, 124.0, 126.4, 127.1, 128.5,
130.0, 135.2, 135.7, 148.8, 149.3, 151.4, 152.3, 162.5.
Mass spectrum (LC-HRMS), m/z: 224.0789 [M + H]+.
C13H9N3O. M 224.0779.
2-(o-Fluorophenyl)quinazolin-4(3H)-one
White solid, mp 162–164°C (163–165°C [24]). 1H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 7.33 d (2Harom
(3j).
,
J 8.0 Hz),7.49 t (1Harom, J 8.0 Hz), 7.57 d (1Harom, J
8.0 Hz), 7.70 d (1Harom, J 7.6 Hz), 7.83 t (1Harom, J
8.0 Hz), 7.94 t (1Harom, J 7.6 Hz), 8.25 d (1Harom, J
8.0 Hz), 12.56 br.s (1H, NH). 13C NMR spectrum
(100 MHz, DMSO-d6), δ, ppm: 116.1 d (JCF 21.0 Hz),
121.1, 122.5 d (JCF 12.7 Hz), 123.8, 126.0, 127.7,
131.1, 132.8 d (JCF 8.3 Hz), 134.7, 148.8, 150.0,
159.5 d (JCF 249.1 Hz), 162.3. Mass spectrum (LC-
HRMS), m/z: 241.0742 [M + H]+. C14H9FN2O. M
241.0732.
2-(Furan-2-yl)quinazolin-4(3H)-one (3o). White
solid, mp 275–277°C (274–276°C [24]). 1H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 6.76 t (1H,
Fu-H, J 8.0 Hz), 7.45 t (1Harom, J 8.0 Hz), 7.63 d (1H,
Fu-H, J 8.0 Hz), 7.76 d (1Harom, J 8.0 Hz), 7.84 t (1Harom
,
J 7.6 Hz), 7.97 s (1H, Fu-H), 8.15 d (1Harom, J 7.6 Hz),
12.47 br.s (1H, NH). 13C NMR spectrum (100 MHz,
DMSO-d6), δ, ppm: 113.5, 115.0, 122.3, 127.1, 128.4,
135.7, 145.3, 146.1, 147.6, 149.8, 162.4. Mass spectrum
(LC-HRMS), m/z: 213.0623 [M + H]+. C12H8N2O2. M
213.0619.
2-(o-Chlorophenyl)quinazolin-4(3H)-one
(3k).
White solid, mp 188–190°C (187–189°C [25]). 1H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm: 7.41–7.59 m
(4Harom), 7.87 d (3Harom, J 7.2 Hz), 8.36 d (1Harom, J
6.4 Hz), 12.35 br.s (1H, NH). 13C NMR spectrum
(100 MHz, DMSO-d6), δ, ppm: 121.1, 125.5, 127.1,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 8 2020

A METAL- AND LIGAND-FREE SYNTHESIS OF QUINAZOLIN-4(3H)-ONES
1453
13. Malamas, M.S. and Millen, J., J. Med. Chem., 1991,
vol. 34, p. 1492.
ACKNOWLEDGMENTS
The authors are grateful to DAE-BRNS, Mumbai for
financial assistance [project no. 37(2)/14/02/2014-BRNS].
Mr Bharat Kumar acknowledges the University Grants
Commission for financial support through the Rajiv Gandhi
National Fellowship (project no. RGNF-2015-17-SC-
AND-14252).
https://doi.org/10.1021/jm00108a038
14. De Laszlo, S.E., Quagliato, C.S., Greenlee, W.J.,
Patchett, A.A., Lotti, V.J., Chen, T.B., Scheck, S.A.,
and Faust, A., J. Med. Chem., 1993, vol. 36, p. 3207.
https://doi.org/10.1021/jm00073a024
15. Kikuchi, H., Yamamoto, K., Horoiwa, S., Hirai, S., Kasa-
hara, R., Hariguchi, N., Matsumoto, M., and Oshi-
ma, Y., J. Med. Chem., 2006, vol. 49, p. 4698.
https://doi.org/10.1021/jm0601809
CONFLICT OF INTERESTS
The authors declare no conflict of interest.
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