Supported ceric ammonium nitrate: A highly efficient catalytic system for the synthesis of diversified 2,3-substituted 2,3-dihydroquinazolin-4(1 H)-ones

Article abstract of DOI:10.1016/j.crci.2013.11.008

A practically expeditious protocol has been developed for the cascade synthesis of 2,3 dihydroquinazolin-4(1H)-ones via the condensation of 2-aminobenzamide/2-aminoben-zanilide and aromatic aldehydes using a catalytic amount of silica-supported ceric ammonium nitrate. This method affords rapid transformation at room temperature with good to excellent yields.

Full text of DOI:10.1016/j.crci.2013.11.008

C. R. Chimie 17 (2014) 971–979
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Preliminary communication/Communication
Supported ceric ammonium nitrate: A highly efficient
catalytic system for the synthesis of diversified 2,
3-substituted 2,3-dihydroquinazolin-4(1H)-ones
Someshwar D. Dindulkar a,b, Jeongsu Oh a, Veenita M. Arole b, Yeon Tae Jeong a,
*
a Department of Image Science and Engineering, Pukyong National University, Busan 608-737, Republic of Korea
b Jawaharlal Nehru Engineering College, Aurangabad 431 003, Maharashtra, India
A R T I C L E I N F O
A B S T R A C T
Article history:
A practically expeditious protocol has been developed for the cascade synthesis of 2,3-
dihydroquinazolin-4(1H)-ones via the condensation of 2-aminobenzamide/2-aminoben-
zanilide and aromatic aldehydes using a catalytic amount of silica-supported ceric
ammonium nitrate. This method affords rapid transformation at room temperature with
good to excellent yields.
Received 12 September 2013
Accepted after revision 12 November 2013
Available online 16 July 2014
Keywords:
ß 2013 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
2,3-Dihydroquinazolin-4(1H)-ones
Heterocycles
Heterogeneous catalyst
Ceric ammonium nitrate
Cascade reaction
1. Introduction
Several methods have been reported for the synthesis of
2,3-dihydroquinazolin-4(1H)-one. Among them, the gen-
Quinazoline heterocycles are very well-known six-
membered heterocyclic ring molecules that possess wide
biological properties, such as antitumor, antidefibrillatory,
analgesic, diuretic, antihistaminic, vasodilating, tranquiliz-
ing and antianxiety ones (Fig. 1) [1–9]. Also quinazolines are
oxidized into quinazolin-4(3H)-ones moieties that are, as
growth inhibitors, of great importance in the treatment of
leukemia cells, and are also used as poly(ADP-ribose)poly-
merase-1 inhibitors [10,11].Also quinazoline derivatives were
found to be useful as fungicides, bactericides, insecticides, and
plant-growth regulators [12]. Some of them display good
pharmacological properties, such as sedative, anticholinester-
ase, hypotensive, soporific, antispasmodic, tranquilizing,
muscle relaxing, antirheumatic, diuretic, antimalarial ones,
as well as other activities [13,14].
eral method includes the reductive cyclization of alde-
hydes or ketones with 2-aminobenzamide in the presence
of acid catalysts, such as cyanuric chloride, ZrCl4, cerium
ammonium nitrate, PPA–SiO2, and gallium triflate [15–19].
Very recently, Ramesh et al. reported efficient methodol-
ogies for the synthesis of 2,3-dihydroquinazolin-4(1H)-
ones using the three-component aniline/isatoic anhydride/
aldehyde system and also the two-component aldehyde/
anthranilamide system catalyzed by
b-cyclodextrin as a
reusable catalyst [20,21]. Also there are some methodol-
ogies that were reported recently using two-component or
three-component systems in aqueous solutions, ionic
liquids, and organic media at high temperature [22–26].
Also Wang et al. reported a manual grinding technique
using CAN catalyst, which has some limitations, such as
long reaction times, high temperatures, and, practically,
the fact that the yield and time needed for manual grinding
is variable because of grinding inconsistency [17].
Despite most of the reported protocols give good yields,
there are some limitations associated with the reaction
*
Corresponding author.
E-mail address: ytjeong@pknu.ac.kr (Y.T. Jeong).
1631-0748/$ – see front matter ß 2013 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2013.11.008

972
S.D. Dindulkar et al. / C. R. Chimie 17 (2014) 971–979
O
O
NH
NH
O
OCH3
N
H
N
H
S
Antibacterial
Antimitotic
NO2
O
O
NH
N
N
H
N
R
COCH2Cl
Antimitotic
Antifibrillatory
Fig. 1. Reported biologically active quinazolinone and quinazolinone-based molecules.
system, such as prolonged reaction times, high tempera-
tures and the need for high catalyst loading. Therefore, the
development of an efficient, cost effective and high-yield
protocol for the synthesis of 2,3-dihydroquinazolin-4(1H)-
ones is of great interest, with significant demand from the
medicinal industries.
We decided to investigate the efficiency of the
supported metal Lewis acid catalyst for the synthesis of
2,3-dihydroquinazolin-4(1H)-ones. With this aim, we
synthesized a variety of silica-supported heterogeneous
catalysts for this one-pot synthesis, and we established an
efficient methodology for the cascade synthesis of
2,3-dihydroquinazolin-4(1H)-ones from aldehydes and
2-aminobenamide/2-aminobenzanilide using CANÁSiO2
as an expeditious catalyst at ambient temperature, with
good yields (Scheme 1).
formation has been described [27–29]. However, the
application of CAN (ceric ammonium nitrate) is limited
due to its poor solubility in common organic solvents.
Therefore, adopting silica as the supporting material has
been reported as a good alternative [30–33]. Silica gel-
supported ceric ammonium nitrate (CANÁSiO2) proximates
the reactant, which fastens electron-transfer processes
between reactants, and further enhances the rate of
reaction with higher efficiency and thus with shorter
reaction times. Moreover, the use of a heterogeneous metal
Lewis catalyst instead of traditional homogeneous metal
Lewis and Brønsted acid catalysts could be a more
environmental friendly alternative.
In connection with our ongoing research on cost
effective methodologies, we discovered a new reaction
system for the synthesis of a variety of organic compounds
of therapeutic and industrial significance, which are key
intermediates for multistep synthesis. In addition, we have
implemented a number of green strategies in organic
transformations using environmental friendly catalytic
reaction conditions [34–38]. Herein, we carried out the
development of an efficient practical methodology for the
Cerium (IV) ammonium nitrate (CAN) is a versatile
catalyst, which has been widely used in organic transfor-
mations due to its many advantages, such as high
reactivity, ease of storage, low cost and commercial
availability. The use of this reagent for numerous
transformations involving C–C, C–O, C–N, and C–S bond
O
CHO
O
R1
R1
CAN.SiO2
ACN, rt
N
H
N
+
NH2
N
H
R
R
R = H, Cl, Br, OEt, OMe, NO2, i-Pr, OH, F,
R1= H, Ph
Scheme 1. (Color online.) Synthesis of 2,3-dihydroquinazolin-4(1H)-ones.

S.D. Dindulkar et al. / C. R. Chimie 17 (2014) 971–979
973
one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-ones by
the reductive condensation of 2-aminobenzamide/2-ami-
nobenzanilide and benzaldehyde using various supported
catalysts. The best results were obtained when using
CANÁSiO2 (containing 5 mol% CAN) at room temperature.
Once we had found CANÁSiO2 as the best catalyst for this
reaction in toluene as a solvent, the solvent optimization
was carried out by screening various solvents, such as
EtOH, CH3CN, DCM, chloroform, and water at room
temperature. Among all the screened solvents, it was
found that acetonitrile is the most suitable one for this
reaction: it gives a maximum yield in short times with an
easy work-up procedure. It is worthy to note that when we
performed the reaction in aqueous media (warm condi-
tions), the reaction was completed with a moderate yield,
but took a long time as compared to acetonitrile media.
After optimization of the solvent system, the optimization
of the appropriate catalyst loading was carried out.
2. Results and discussion
The optimization of the reaction conditions begins with
the investigation of the effect of various prepared
heterogeneous catalysts and solvents (Table 1). We first
carried out a model reaction between 2-aminobenzamide
(5 mmol) and benzaldehyde (5 mmol) in the presence of
In an attempt to optimize the catalyst, a model reaction
was carried out in the absence of catalyst and with 10 mol%
of ceric ammonium nitrate supported on silica at room
temperature in acetonitrile (Table 1, entries 12, 13). It was
found that in the absence of catalyst, less than 40% of yield
was observed even after 12 h of stirring of the reaction
medium at room temperature. A larger amount of
catalyst loading (10 mol%) neither increases the yield
nor shortens the conversion time (Table 1, entry 13). So,
an amount of 5 mol% of CAN loaded on silica was found to
be the optimal quantity sufficient to convert the reactant
into the product. Furthermore, CANÁSiO2 was recovered
simply by dissolving the reaction mixture in acetone and
filtering it to get a solid heterogeneous catalyst with
excellent yields (about ꢀ 92%). The crude product was
obtained by evaporating acetone, and was further
purified by recrystallization from ethanol.
5
mol% of catalyst using various solvents at room
temperature in the air. Also a test reaction was performed
without catalyst to find out the actual role of the catalyst in
this cascade synthesis. We observed that less than 40% of
the product was obtained in the absence of catalyst, even
after 2 h (Table 1, entry 12). In search of an effective,
catalytic system for the synthesis of quinazolin-4(1H)-
ones, the test reaction was performed using benzaldehyde
(0.5 mmol), 2-aminobenzamide (0.5 mmol) with different
supported metal acid catalysts, such as Cu(OTf)2ÁSiO2,
Zn(OTf)2ÁSiO2, TiO2ÁSiO2, CANÁSiO2 and ZnCl2ÁSiO2 (Table
1). Among all screened catalysts, CANÁSiO2 (containing
5 mol% CAN) at room temperature gave the best yield in
short reaction time (Table 1, entry 3). In contrast, TiO2ÁSiO2,
Zn(OTf)2ÁSiO2, and ZnCl2ÁSiO2 did not afford the desired
product in good yields. The careful analysis of the screened
supported Lewis acid catalysts shows that silica-supported
metal catalysts such as CANÁSiO2 and Cu(OTf)2ÁSiO2 were
more effective than other silica-supported metal Lewis
acid catalysts, but promising results were obtained with
the silica-supported ceric ammonium nitrate catalyst with
shorter times and better yields.
The reusability of the catalyst was tested for two more
reaction cycles. The recovered catalyst was reused as in
other two consecutive reaction cycles accordingly. After
the first fresh run with 88% yield, the recovered catalyst
was washed, dried, and used for a second and a third times.
Table 1
Optimization of reaction condition using various solvent and catalyst.
O
CHO
O
NH2
NH2
NH
+
N
H
1
2
3
Entry
Catalysta (5 mol%)
Solvent
Time
Yieldc
1
Cu(OTf)2ÁSiO2
Zn(OTf)2ÁSiO2
CANÁSiO2
ZnCl2ÁSiO2
TiO2ÁSiO2
CANÁSiO2
CANÁSiO2
CANÁSiO2
CANÁSiO2
CANÁSiO2
CANÁSiO2
–
Toluene
Toluene
Toluene
Toluene
Toluene
DCM
60 min
120 min
60 min
120 min
120 min
60 min
20 min
180 min
60 min
60 min
60 min
12 h
82
2
68
3
84
4
67
5
58
6
65
7
ACN
88
8
Water
Ethanol
CHCl3
Neat
85
9
68
10
11
12
13b
61
No reaction
< 40
ACN
CANÁSiO2
ACN
60 min
ꢁ 90
a
Reaction conditions: all reactions were carried out at room temperature using benzaldehyde (0.5 mmol), 2-aminobenzamide (0.5 mmol) and 5 mol% of
catalyst.
b
CANÁSiO2 containing 10 mol% CAN.
c
Isolated yield.

974
S.D. Dindulkar et al. / C. R. Chimie 17 (2014) 971–979
Table 2
the synthesis of a variety of 2-aryl-2,3-dihydroquinazolin-
4(1H)-ones/2,3-diaryl-2,3-dihydroquinazolin-4(1H)-ones
derivatives using 2-aminobenzamide/2-aminobenzanilide
and various electron-donating moieties, such as methoxy,
ethoxy, and isopropyl, as well as electron-withdrawing
compounds, such as nitro-, bromo- and chloro-substituted
aromatic aldehydes (Table 3). Various aromatic aldehydes
with different substituent at ortho, meta or para-positions
show equal ease towards the product formation in high
yields (78–94% yields, Table 3). In contrast, aromatic
aldehydes having groups like Cl, F, Br, MeO, EtO, and nitro
showed better reactivity, and the reactions were com-
pleted in shorter times. Particularly, the reaction with 2-
aminobenzanilide afforded the desired product in moder-
ate yields. The overall study made us conclude that
CANÁSiO2 is the best catalytic system for this cascade
Reuse of CANÁSiO2 in the synthesis of 2,3-dihydro-2-phenylquinazolin-
4(1H)-one.
Entry
Reaction cycle
Yield (%)a
1
2
3
Ist (‘‘fresh’’ run)
IInd cycle
88
86
78
IIIrd cycle
a
Isolated yield.
Yields of 86 and 78% were obtained respectively, thus
proving the lesser leaching of the catalyst in the solvent
and the catalyst’s reusability (Table 2).
Once the effective catalytic amount of the CANÁSiO2
catalyst (containing 0.05 equiv. of CAN) was proven, we
extended, to further generalize this, this methodology to
Table 3
Synthesis of diversified quinazolin-4(1H)-one via Scheme 1a.
Entry
1
Aldehyde
C6H5
Product
Time (min)
20
Yield (%)b
88
Reportedc
21
O
NH
NH
N
H
2
3
4
4-Cl–C6H4
4-Br–C6H4
4-OEt–C6H4
10
20
40
86
84
94
23
21
–
O
N
H
Cl
O
NH
NH
N
H
Br
O
N
H
OEt
5
6
2-OMe–C6H4
20
15
89
92
21
22
O
NH OMe
N
H
4-OMe–C6H4
O
NH
N
H
OMe
OMe
7
3-OMe–C6H4
40
86
3
O
NH
N
H

S.D. Dindulkar et al. / C. R. Chimie 17 (2014) 971–979
975
Table 3 (Continued )
Entry
8
Aldehyde
Product
Time (min)
10
Yield (%)b
92
Reportedc
4-NO2–C6H4
21
O
NH
NH
N
H
NO2
9
4-iPr–C6H4
10
90
15
O
N
H
10
4-OH–C6H4
25
83
21
O
NH
N
H
OH
11
12
2-F–C6H4
30
20
90
88
15
23
O
NH F
NH
N
H
3-F–C6H4
O
F
N
H
13
14
C6H5
40
30
84
87
24
25
O
N
N
N
H
4-Br–C6H4
O
N
H
Br
Cl
15
4-Cl–C6H4
30
92
24
O
N
N
H
16
2-F–C6H4
50
78
26
O
N
F
N
H
a
All reactions were carried out at room temperature using benzaldehyde (0.5 mmol), 2-aminobenzamide (0.5 mmol) and CANÁSiO2 (containing 5 mol%
CAN) in acetonitrile at room temperature.
b
Isolated yield.
c
Compound reported in the literature.

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S.D. Dindulkar et al. / C. R. Chimie 17 (2014) 971–979
SiO2
CeIV
SiO2
CeIV
O
O
O
SiO2
CeIV
HO
NH2
NH2
H
NH
+
-H2O
N
NH2
N
1
2
CeIV
SiO2
O
OH
SiO2
CeIV
NH
NH
1,5-H+ transfer
N
H
N
Final product
3
Scheme 2. (Color online). A possible mechanism for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones.
synthesis, as it gives excellent yields in very short
durations in the milder conditions.
4. Experimental
A possible mechanism for this one-pot reaction has
been postulated on the basis of the reported literature
[15,39]. The reaction proceeds with the formation of imine
with the amine of 2-aminobenzamide/2-aminobenzani-
lide and benzaldehydes promoted by CANÁSiO2. Inter-
mediate 1 could be tautomerized in the presence of
CANÁSiO2 to give intermediate 2. The formed intermediate
2 could be activated by CANÁSiO2, which will be further
converted into intermediate 3 by intramolecular nucleo-
phile attack of the nitrogen on the imine carbon. Finally,
we obtained the desired product 2,3-dihydroquinazolin-
4(1H)-ones by a simple 1,5-proton transfer (Scheme 2).
All new compounds were completely characterized by
their spectral properties, as 1H-, 13C-NMR and mass
analysis were carried out.
4.1. General
All chemicals were purchased from Aldrich and Alfa
Aesar Chemicals. NMR spectra were recorded in ppm in
DMSO-d6 on a Jeol JNM ECP 400 NMR instrument using
TMS as an internal standard. EI/MS were recorded on a Jeol
JMS-700 mass spectrometer. The melting points were
taken in open capillaries and are uncorrected; an Electro-
thermal-9100 (Japan) instrument was used to determine
the melting point of the compounds.
4.2. General procedure for the synthesis of the silica-
supported ceric ammonium nitrate catalyst
A supported ceric ammonium nitrate catalyst was
prepared by adopting the procedure in the literature [30].
Neutral silica gel (9.01 g, Merck Kieselgel 60, particle size
0.063–0.200 mm, 70–230 mesh) was mixed with
a
3. Conclusion
solution of CAN (1.02 g) in water (2.0 mL). Evaporation
of water under reduced pressure gave a dry yellowish
powder, which contained 10% (by weight) of CAN.
According to Hwu et al., this reagent was found active
for at least six months of storage in a well-capped bottle.
In conclusion, we have successfully developed an
efficient protocol for the synthesis of 2,3-dihydroquina-
zolin-4(1H)-ones using CANÁSiO2 as an expeditious reu-
sable catalyst at room temperature. Compared to the
previously known methodologies, silica-supported CAN
was conveniently prepared without any special precau-
tion. A wide range of products bearing different functio-
nalized groups is conveniently accessible in reasonable to
excellent isolated yields. The method offers several
advantages, including room-temperature conditions, high
yield of products, short reaction times, recyclability of the
catalyst, and the fact that the residue is crystallized from
ethanol to give the pure product without further column
purification.
4.3. General experimental procedure for the synthesis of 2,3-
dihydroquinazolin-4(1H)-ones using CANÁSiO2
The standard procedure was followed by the use of 1
(3.6 mol), 2 (3.6 mol), CANÁSiO2 0.401 g (containing 0.100 g
of CAN, 0.18 mol, 0.05 equiv.), and acetonitrile (5.0 mL).
After the reaction mixture had been stirred for certain
period as indicated in Table 3, and completion of the
reaction as indicated by TLC, the reaction mixture was

S.D. Dindulkar et al. / C. R. Chimie 17 (2014) 971–979
977
dissolved in acetone and the catalyst was recovered by
filtration. The solvent was then evaporated under vacuum
to afford the crude product. The obtained crude product
was further recrystallized from ethanol to get the pure
final product. All new compounds were completely
characterized by 1H/13C NMR and EI/MS data of few
selected new compounds are given below. The scanned
spectra of all compounds are provided as supporting
information (Appendix B).
DMSO-d6) dC: 163.8, 156.3, 147.9, 133.2, 129.6, 128.9,
126.8, 120.1, 117.0, 114.5, 111.0, 61.0, 55.51 ppm.
4.3.6. 2,3-Dihydro-2-(4-methoxyphenyl)quinazolin-4(1H)-
one (6, C15H14N2O2)
Rf = 0.38 (hexane/ethyl acetate 70:30%), pale yellow
solid; Mp178–180 8C; yield 92%. 1H NMR (400 MHz,
DMSO-d6) d: 8.19 (s, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.42 (d,
J = 8.8 Hz, 2H), 7.24 (br s, 1H), 6.94 (d, J = 8.8 Hz, 3H), 6.75
(d, J = 8.01 Hz, 1H), 6.67 (t, J = 7.5 Hz, 1H), 5.71 (s, 1H), 3.74
(s, 3H) ppm; 13C NMR (100.5 MHz, DMSO-d6)
dC: 163.7,
4.3.1. 2,3-Dihydro-2-phenylquinazolin-4(1H)-one (1,
C
14H12N2O)
159.4, 148.0, 133.2, 128.2, 127.3, 117.0, 114.9, 114.4, 113.6,
66.3, 55.1 ppm.
Rf = 0.29 (hexane/ethyl acetate 70:30%), Pale yellow
solid; Mp. 220–222 8C; yield 88%. 1H NMR (400 MHz,
DMSO-d6)
d
: 8.32 (br s, 1H), 7.65 (d, J = 7.6 Hz, 1H), 7.52 (d,
4.3.7. 2,3-Dihydro-2-(3-methoxyphenyl)quinazolin-4(1H)-
one (7, C15H14N2O2)
Rf = 0.28 (hexane/ethyl acetate 70:30%), yellow solid;
Mp. 142–144 8C; yield 86%. 1H NMR (400 MHz, DMSO-d6)
J = 7.3 Hz, 2H), 7.41–7.33 (m, 3H), 7.26 (t, J = 7.5 Hz, 1H),
7.14 (br s, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.69 (t, J = 7.5 Hz, 1H),
5.79 (s, 1H) ppm; 13C NMR (100.5 MHz, DMSO-d6) dC
:
163.6, 147.8, 141.6, 133.3, 128.4, 128.3, 127.3, 126.8, 117.1,
114.9, 114.4, 66.6 ppm.
d: 8.30 (s, 1H), 7.62 (unresolved dd, 1H), 7.30–7.22 (m, 2H),
7.12 (br s, 1H), 7.07–7.06 (m, 2H), 6.90 (unresolved dd, 1H),
6.76 (d, J = 8.0 Hz, 1H), 6.67 (t, J = 7.5 Hz, 1H), 5.73 (d,
J = 1.8 Hz, 1H), 3.74 (s, 3H) ppm; 13C NMR (100.5 MHz,
4.3.2. 2-(4-Chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one
(2, C14H11ClN2O)
DMSO-d6)
dC: 163.5, 159.2, 147.7, 143.3, 133.2, 129.4,
Rf = 0.38 (hexane/ethyl acetate 70:30%), pale yellow
solid; Mp. 203–205 8C; yield 86%. 1H NMR (400 MHz,
127.3, 118.9, 117.0, 114.3, 113.6, 112.5, 66.2, 55.0 ppm.
DMSO-d6)
d
: 8.35 (br s, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.49 (dd,
4.3.8. 2,3-Dihydro-2-(4-nitrophenyl)quinazolin-4(1H)-one
(8, C14H11N3O3)
Rf = 0.27 (hexane/ethyl acetate 70:30%), yellow solid;
Mp. 183–185 8C; yield 92%. 1H NMR (400 MHz, DMSO-d6)
J = 8.4, 26 Hz, 4H), 7.25 (t, J = 7.6 Hz, 1H), 7.15 (br s, 1H),
6.76 (d, J = 8.4 Hz, 1H), 6.69 (t, J = 7.5 Hz, 1H), 5.79 (s, 1H)
ppm; 13C NMR (100.5 MHz, DMSO-d6)
dC: 163.5, 147.6,
140.6, 133.3, 132.9, 128.7, 128.3, 127.3, 117.2, 114.9, 114.4,
65.7 ppm.
d: 8.53 (br s, 1H), 8.24 (d, J = 9.6 Hz, 2H), 7.75 (d, J = 8.8 Hz,
2H), 7.62 (dd, J = 1.4, 8.0 Hz, 1H), 7.33 (br s, 1H), 7.28–7.24
(m, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.70–6.66 (m, 1H), 5.92 (s,
1H) ppm; 13C NMR (100.5 MHz, DMSO-d6)
dC: 163.3, 149.3,
147.2, 133.5, 128.0, 127.4, 123.5, 117.4, 114.9, 114.5,
65.3 ppm.
4.3.3. 2-(4-Bromophenyl)-2,3-dihydroquinazolin-4(1H)-one
(3, C14H11BrN2O)
Rf = 0.36 (hexane/ethyl acetate 70:30%), pale green
solid; Mp. 193–195 8C; yield 84%. 1H NMR (400 MHz,
DMSO-d6)
J = 8.4 Hz, 2H), 7.25 (t, J = 7.7 Hz, 1H), 7.16 (br s, 1H), 6.76 (d,
J = 8.0 Hz, 1H), 6.69 (t, J = 7.5 Hz, 1H), 5.77 (s, 1H) ppm; 13
NMR (100.5 MHz, DMSO-d6) C: 163.4, 147.6, 141.1, 133.4,
d
: 8.35 (br s, 1H), 7.63–7.58 (m, 3H), 7.45 (d,
4.3.9. 2,3-Dihydro-2-(4-isopropylphenyl)quinazolin-4(1H)-
one (9, C17H18N2O)
Rf = 0.29 (hexane/ethyl acetate 70:30%), pale yellow
solid; Mp. 159–161 8C; yield 90%. 1H NMR (400 MHz,
C
d
131.2, 129.0, 127.3, 121.5, 117.2, 114.9, 114.4, 65.7 ppm.
DMSO-d6) d: 8.21 (br s, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.42 (d,
J = 8.4 Hz, 2H), 7.27-7.21 (m, 3H), 7.02 (br s, 1H), 6.73 (d,
J = 8.0 Hz, 1H), 6.67 (t, J = 7.7 Hz, 1H), 5.71 (s, 1H), 2.93–2.83
(m, 1H), 1.18 (d, J = 6.9 Hz, 6H) ppm; 13C NMR (100.5 MHz,
4.3.4. 2-(4-Ethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
(4, C16H16N2O2)
Rf = 0.38 (hexane/ethyl acetate 70:30%), yellow solid;
Mp. 122–124 8C; yield 94%; EIMS m/z 268 [M]+. 1H NMR
DMSO-d6) dC: 163.6, 148.8, 147.9, 138.9, 133.2, 127.3,
126.9, 126.2, 117.0, 114.9, 114.3, 66.5, 33.2, 23.8 ppm.
(400 MHz, DMSO-d6) d: 8.17 (br s, 1H), 7.93 (br s, 1H), 7.39
(d, J = 8.4 Hz, 1H), 7.25–7.21 (m, 3H), 6.91 (d, J = 11.6 Hz,
1H), 6.74 (d, J = 8.0 Hz, 1H), 6.68–6.60 (m, 2H), 5.70 (s, 1H),
4.03–3.79 (q, 2H), 1.30 (t, J = 6.9, 3H) ppm; 13C NMR
4.3.10. 2,3-Dihydro-2-(4-hydroxyphenyl)quinazolin-4(1H)-
one (10, C14H12N2O2)
Rf = 0.28 (hexane/ethyl acetate 70:30%), yellow solid;
Mp. 192–194 8C; yield 83%. 1H NMR (400 MHz, DMSO-d6)
(100.5 MHz, DMSO-d6) dC: 163.0, 147.0, 133.1, 128.1, 127.3,
127.1, 116.4, 114.4, 114.2, 114.0, 66.8, 63.0, 14.6 ppm.
d: 9.54 (br s, 1H), 8.12 (s, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.32
(d, J = 8.0 Hz, 2H), 7.24 (t, J = 7.5 Hz, 1H), 6.94 (br s, 1H),
6.79–6.74 (m, 3H), 6.58 (t, J = 7.5 Hz, 1H), 5.67 (s, 1H) ppm;
13C NMR (100.5 MHz, DMSO-d6)
dC: 163.8, 157.7, 148.1,
4.3.5. 2,3-Dihydro-2-(2-methoxyphenyl)quinazolin-4(1H)-
one (5, C15H14N2O2)
Rf = 0.35 (hexane/ethyl acetate 70:30%), yellow solid;
Mp. 123–125 8C; yield 89%. 1H NMR (400 MHz, DMSO-d6)
133.2, 131.6, 128.3, 127.3, 117.0, 114.9, 114.4, 66.7 ppm.
d
: 8.04 (br s, 1H), 7.65 (d, J = 7.3 Hz, 1H), 7.42 (d, J = 7.3 Hz,
4.3.11. 2-(2-Fluorophenyl)-2,3-dihydroquinazolin-4(1H)-
one (11, C14H11FN2O)
Rf = 0.28 (hexane/ethyl acetate 70:30%), pale yellow
solid; Mp. 185–187 8C; yield 90%. 1H NMR (400 MHz,
1H), 7.33–7.19 (m, 3H), 7.03 (t, J = 8.0 Hz, 1H), 6.94 (t,
J = 7.5, 1H), 6.79 (d, J = 8.0 Hz, 1H), 6.67 (t, J = 7.5 Hz, 1H),
6.05 (s, 1H), 3.82 (s, 3H) ppm; 13C NMR (100.5 MHz,

978
S.D. Dindulkar et al. / C. R. Chimie 17 (2014) 971–979
DMSO-d6)
d
: 8.26 (s, 1H), 7.62 (unresolved dd, 1H), 7.57–
126.1, 122.6, 117.7, 115.3, 115.0, 114.8, 113.6, 114.4,
71.8 ppm.
7.53 (m, 1H), 7.43–7.38 (m, 1H), 7.27–7.20 (m, 3H), 7.64 (s,
1H), 6.76 (d, J = 8.0 Hz, 1H), 6.72–6.68 (m, 1H), 6.06 (s, 1H)
ppm; 13C NMR (100.5 MHz, DMSO-d6)
dC: 163.5, 147.6,
Acknowledgements
133.4, 130.6, 128.3, 127.3, 124.3, 117.3, 115.7, 115.4, 114.6,
114.4, 60.8 ppm.
This research work was supported by the Industrial
Technology Development Program, which was conducted
by the Ministry of Knowledge Economy of the Korean
Government.
4.3.12. 2-(3-Fluorophenyl)-2,3-dihydroquinazolin-4(1H)-
one (12, C14H11FN2O)
Rf = 0.27 (hexane/ethyl acetate 70:30%), pale yellow
solid; Mp. 258–260 8C; yield 88%. 1H NMR (400 MHz,
Appendix A. Supplementary data
DMSO-d6)
7.16 (m, 6H), 6.78 (d, J = 8.0 Hz, 1H), 6.68 (t, J = 7.8 Hz, 1H),
5.80 (s, 1H) ppm; 13C NMR (100.5 MHz, DMSO-d6) dC
163.4, 147.5, 144.6, 133.4, 130.3, 127.3, 122.7, 117.3, 115.2,
114.9, 114.4, 113.6,113.4, 65.6 ppm.
d: 8.41 (s, 1H), 7.60 (unresolved dd, 1H), 7.43–
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/
j.crci.2013.11.008.
:
References
4.3.13. 2,3-Dihydro-2,3-diphenylquinazolin-4(1H)-one (13,
C
20H16N2O)
[1] R.J. Alaimo, H.E. Russell, J. Med. Chem. 15 (1972) 335.
[2] H.A. Parish, R.D. Gilliom, W.P. Purcell, R.K. Browne, R.F. Spirk, H.D.
White, J. Med. Chem. 25 (1982) 98.
[3] M.J. Hour, L.J. Huang, S.C. Kuo, Y. Xia, K. Bastow, Y. Nakanishi, E. Hamel,
K.H. Lee, J. Med. Chem. 43 (2000) 4479.
Rf = 0.28 (hexane/ethyl acetate 70:30%), blackish
green solid; Mp. 215–217 8C; yield 84%. 1H NMR
(400 MHz, DMSO-d6)
d: 7.75 (dd, J = 1.4, 7.7 Hz, 1H),
[4] L.B. Helen, M.B. George, D. Natasha, J.D. Hazel, J.F. Elizabeth, J.G. Philip,
R.H. Duncan, F.H. Alan, J.M. Michael, M. Trevor, R.P. William, J.R.
Andrew, C.R. Nicholas, D.R. Marianna, S. Andrew, J.T. Alicia, M.W.
Justine, C.W. Sophie, Bioorg. Med. Chem. Lett. 15 (2005) 5335.
[5] G. Bonola, R.P. Da, M.J. Magistretti, E. Massarani, I. Setnikar, J. Med.
Chem. 11 (1968) 1136.
7.66 (d, J = 2.5 Hz, 1H), 7.40–7.16 (m, 11H), 6.78 (d,
J = 8.0 Hz, 1H), 6.74–6.70 (m, 1H), 6.29 (d, J = 2.6 Hz, 1H)
ppm; 13C NMR (100.5 MHz, DMSO-d6)
dC: 162.2, 146.5,
140.6, 133.7, 128.5, 128.3, 128.2, 127.9, 126.5, 126.2,
125.9, 117.4, 114.7, 72.5 ppm.
[6] K. Okumura, T. Oine, Y. Yamada, G. Hayashi, M. Nakama, J. Med. Chem.
11 (1968) 348.
[7] E. Cohen, B. Klarberg, J.R. Vaughan, J. Am. Chem. Soc. 81 (1959) 5508.
[8] V. Alagarsamy, V.R. Solomon, M. Murugan, Bioorg. Med. Chem. 15
(2007) 4009.
[9] J.I. Levin, P.I. Chan, T. Bailey, A.S. Katocs, A.M. Venkatesan, Bioorg. Med.
Chem. Lett. 4 (1994) 1141.
4.3.14. 2-(4-Bromophenyl)-2,3-dihydro-3-
phenylquinazolin-4(1H)-one (14, C20H15BrN2O)
Rf = 0.27 (hexane/ethyl acetate 70:30%), pale yellow
solid; Mp. 221–223 8C; yield 87%. 1H NMR (400 MHz,
[10] J.B. Jiang, D.P. Hesson, B.A. Dusak, D.L. Dexter, G.J. Kang, E. Hamel, J.
Med. Chem. 33 (1990) 1721.
DMSO-d6)
7.51 (d, J = 8.4 Hz, 2H), 7.35–7.17 (m, 8H), 6.78–6.71 (m,
2H), 6.31 (s, 1H) ppm; 13C NMR (100.5 MHz, DMSO-d6) dC
d: 7.74 (dd, J = 1.0, 7.7 Hz, 1H), 7.65 (br s, 1H),
[11] H. Kouji, K. Yoshiyuki, Y. Hirofumi, I. Junya, K. Kazunori, M. Kenji, O.
Mitsuru, K. Takayoshi, I. Akinori, M. Kayoko, Y. Syunji, M. Nobuya, T.
Yoshinori, M. Hiroshi, J. Med. Chem. 47 (2004) 4151.
[12] G. Ouyang, P. Zhang, G. Xu, B. Song, S. Yang, L. Jin, W. Xue, D. Hu, P. Lu, Z.
Chen, Molecules 11 (2006) 383.
:
162.1, 146.3, 140.5, 140.0, 133.8, 131.2, 128.8, 128.6, 127.9,
126.1, 126.0, 121.5, 117.6, 114.8, 71.9 ppm.
[13] T. Hisano, K. Shoji, M. Ichikawa, Org. Prep. Proc. Int. 4 (1975) 271.
[14] R.S.H. Kuryazov, N.S. Mukhamedov, K.M. Shakhidoyatov, Chem. Het-
erocycl. Compd. 44 (2008) 324.
4.3.15. 2-(4-Chlorophenyl)-2,3-dihydro-3-
phenylquinazolin-4(1H)-one (15, C20H15ClN2O)
Rf = 0.28 (hexane/ethyl acetate 70:30%), pale pink solid;
Mp. 219–221 8C; yield 92%. 1H NMR (400 MHz, DMSO-d6)
[15] M. Sharma, S. Pandey, K. Chauhan, D. Sharma, B. Kumar, P.M.S. Chau-
han, J. Org. Chem. 77 (2012) 929.
[16] A.A. Mohammad, S. Elahe, Chin. Chem. Lett. 22 (2011) 1163.
[17] M. Wang, J.J. Gao, Z.G. Song, L. Wang, Chem. Heterocycl. Compd. 47
(2011) 851.
d: 7.75 (d, J = 7.7 Hz, 1H), 7.66 (d, J = 2.5 Hz, 1H), 7.41–7.25
[18] H.R. Shaterian, A.R. Oveisi, Chin. J. Chem. 27 (2009) 2418.
[19] C. Jiuxi, W. Dengze, H. Fei, L. Miaochang, W. Huayue, D. Jinchang, S.
Weike, Tetrahedron Lett. 49 (2008) 3814.
[20] K. Ramesh, K. Karnakar, G. Satish, K.V.R. Harsha, Y.V.D. Nageswar,
Tetrahedron Lett. 53 (2012) 6095.
(m, 9H), 7.19 (t, J = 7.1 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.73
(t, J = 7.7 Hz, 1H), 6.32 (d, J = 2.5 Hz, 1H) ppm; 13C NMR
(100.5 MHz, DMSO-d6)
dC: 162.1, 146.4, 140.6, 139.6,
133.8, 132.9, 128.6, 128.5, 128.3, 127.9, 126.2, 126.0, 117.6,
114.8, 71.9 ppm.
[21] K. Ramesh, K. Karnakar, G. Satish, B.S.P. Anil Kumar, Y.V.D. Nageswar,
Tetrahedron Lett. 53 (2012) 6936.
[22] C. Yijia, S. Weiguang, L. Min, H. Lihong, Tetrahedron. Lett. 53 (2012)
5923.
4.3.16. 2-(2-Fluorophenyl)-2,3-dihydro-3-phenylquinazolin-
4(1H)-one (16, C20H15FN2O)
Rf = 0.30 (hexane/ethyl acetate 70:30%), blackish green
solid; Mp. 195–197 8C; yield 78%. 1H NMR (400 MHz,
[23] M. Prakash, V. Kesavan, Org. Lett. 14 (2012) 1896.
[24] M. Wang, T.T. Zhang, Y. Liang, J.J. Gao, Monatsh. Chem. 143 (2012) 835.
[25] S.T. Ali, B. Shiva, Monatsh. Chem. 141 (2010) 1113.
[26] S.Y. Wang, K. Wang Xiangshan, Chin. J. Org. Chem. 31 (2011) 1235.
[27] X. Xiaoping, J. Ran, Z. Xiaoguang, Y. Liu, J. Shunjun, Z. Yong, Tetrahedron
665 (2009) 877.
DMSO-d6) d: 7.74 (unresolved dd 1H), 7.70 (d, J = 2.56 Hz,
[28] J.T. Wang, X.D. Jia, L.J. Peng, L.M. Wu, Chin. Chem. Lett. 22 (2011) 655.
[29] R. Jiang, Y. Zhang, Y.C. Shen, X. Zhu, X.P. Xu, S.J. Ji, Tetrahedron 66 (2010)
4073.
[30] H.A. Mohammed, N. Melinda, B. Gary Daniel, Synth. Commun. 36
(2006) 1751.
1H) 7.37–7.18 (m, 9H), 7.12–7.07 (m, 1H), 6.79 (d,
J = 8.0 Hz, 1H), 6.74 (t, J = 7.8 Hz, 1H), 6.35 (d, J = 2.9 Hz,
1H) ppm; 13C NMR (100.5 MHz, DMSO-d6)
d
C: 162.1,
146.4, 143.3, 140.6, 133.8, 130.3, 128.6, 128.5, 127.9,

S.D. Dindulkar et al. / C. R. Chimie 17 (2014) 971–979
979
[31] R.H. Jih, L.J. Moti, T. Fu-Yuan, T. Shwu-Chen, B. Arumugham, H.H.
Gholam, J. Org. Chem. 65 (2006) 5077.
[36] S.D. Dindulkar, V.G. Puranik, Y.T. Jeong, Tetrahedron. Lett. 53 (2012)
4376.
[32] C. Philippe, C. Jean-Pierre, Tetrahedron Lett. 33 (1992) 3855.
[33] H.M. Chawla, R.S. Mittal, Synthesis 1 (1985) 70.
[34] V.R. Mudumala, K. Jongsik, Y.T. Jeong, J. Fluorine Chem. 135 (2012) 155.
[35] S.D. Dindulkar, V.R. Mudumala, Y.T. Jeong, Catal. Commun. 17 (2012)
114.
[37] R.M. Veeranarayana, S.R.G. Chandra, Y.T. Jeong, Tetrahedron 68 (2012)
6820.
[38] V.R. Mudumala, S.D. Dindulkar, Y.T. Jeong, Tetrahedron. Lett. 52 (2011) 4764.
[39] C. Jiuxi, W. Dengze, H. Fei, L. Miaochang, W. Huayue, D. Jinchang, S.
Weike, Tetrahedron. Lett. 49 (2008) 3814.