An efficient synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives under catalyst-free and solvent-free conditions

Article abstract of DOI:10.1002/jhet.592

Figure represented. A simple, efficient and convenient one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives under solvent-free and catalyst-free conditions by the reaction of aromatic aldehydes, isatoic anhydride, and ammonium acetate was repo

Full text of DOI:10.1002/jhet.592

July 2011
An Efficient Synthesis of 2,3-Dihydroquinazolin-4(1H)-one
Derivatives under Catalyst-Free and Solvent-Free Conditions
957
Lijiu Gao,a Honglou Ji,a Liangce Rong,a,b* Dan Tang,a Yunyun Zha,a
Yanhui Shi,a,b and Shujiang Tua,b
aCollege of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou, Jiangsu
221116, P.R. China
bKey Laboratory of Biotechnology for Medicinal Plant, Xuzhou Normal University, Xuzhou,
Jiangsu 221116, P.R. China
*E-mail: lcrong2005@yahoo.com
Received February 5, 2010
DOI 10.1002/jhet.592
Published online 11 April 2011 in Wiley Online Library (wileyonlinelibrary.com).
A simple, efficient and convenient one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives
under solvent-free and catalyst-free conditions by the reaction of aromatic aldehydes, isatoic anhydride,
and ammonium acetate was reported. The advantages of this protocol include short reaction time, mild
reaction conditions, easy work-up, high yields, and environmental friendliness.
J. Heterocyclic Chem., 48, 957 (2011).
INTRODUCTION
new 2-aryl-substituted 2,3-dihydroquinazolin-4(1H)-ones
under solvent-free conditions, using molecular iodine as
a catalyst at 110ꢀC within 4–25 min [7]. Several years
ago, we reported one-pot synthesis of quinazolin-4(3H)-
ones and 1,2-dihydroquinazolin-4(3H)-ones using TiCl4-
Zn in anhydrous THF [8]. Some other methods for the
synthesis of 2,3-dihydroquinazolin-4(1H)-ones involved
the condensation of 2-aminobenzamide with aldehydes
or ketones in the presence of various catalysts such as
CuCl2 [9], NH4Cl [10], Sc(OTf)3 [11], and SmI2 [12].
However, many of these methods mentioned above suf-
fer from drawbacks, such as high reaction temperatures,
low yields, or toxic solvents. For example, when NH4Cl
[10] was used as catalyst, the starting material 2-amino-
benzamide was not easy to get, which must be synthe-
sized with several steps. If the reaction was promoted
by TiCl4-Zn [8], it must be proceeded under oxygen-
free and anhydrous conditions. Even little amount of ox-
ygen could stop the reaction from happening. When it
comes to SmI2 [12], the raw material was not easily
obtained, the reaction must be performed under the pro-
tection of dry nitrogen, and the after-treatment of the
reaction was complex. It was time consuming and low
efficiency to adopt such measures as a result of these
severe requirements. Moreover, some catalysts are ex-
pensive and not easily available. And above all, the pri-
mary disadvantages about the reported methods were
that the organic solvent was required, which would pol-
lute our living surroundings.
Compounds with biological activity are often derived
from heterocyclic structures. Heterocycles are an impor-
tant class of substrates that are found in natural products
such as vitamins, hormones, antibiotics, as well as phar-
maceuticals, herbicides, dyes, and many other com-
pounds [1].
2,3-Dihydroquinazolin-4(1H)-one derivatives are an
important class of heterocycles for pharmaceutical
chemistry. They have been reported to exhibit diverse
pharmacological activities and biological activities such
as antitumor activity, diuretic properties, herbicide activ-
ity, and plant growth regulation ability [2].
A number of methods have been reported to prepare
2,3-dihydroquinazolin-4(1H)-one derivatives in the past
few years. The typical procedure for the synthesis of
2,3-dihydroquinazolin-4(1H)-ones involves the conden-
sation reaction of anthranilamide with aldehyde or ke-
tone using p-toluenesulfonic acids as a catalyst under
vigorous conditions [3]. In 2005, Kurth and coworkers
reported a one-pot conversion of 2-nitro-N-arylbenza-
mides to 2,3-dihydroquinazolin-4(1H)-ones using 10
equiv SnCl2 in RCH2OH for 2-day-long refluxing [4]. A
recent report described the preparation of 2,3-dihydro-
quinazolin-4(1H)-ones by one-pot synthesis catalyzed by
Ga(OTf)3 in ethanol [5]. Salehi and coworkers reported
some new one-pot synthesis of these compounds using
different catalysts, such as p-toluenesulfonic acids [6a],
silica sulfuric acid [6b], alum [6c], and Montmorillonite
K-10 [6d]. Rostamizadeh et al. reported the synthesis of
Because of the growing concern for the influence of
the organic solvent on the environment as well as on
C
V
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958
L. Gao, H. Ji, L. Rong, D. Tang, Y. Zha, Y. Shi, and S. Tu
Vol 48
Table 1
The results of synthesis of 2,3-dihydroquinazolin-4(1H)-one.
human body, organic reactions without using conven-
tional organic solvents are of great significance for syn-
thetic organic chemists today. There has been an
upsurge of interest in synthesizing compounds in sol-
vent-free environment during recent years. Compared
with the ways used in the solvent, the solvent-free
approach proceeded more cleanly and provided higher
yields. One-pot transformations, particularly multicom-
ponent reactions (MCRs), are attracting much attention
in modern synthetic organic chemistry [13]. It must be
an ideal process for MCRs, which can be carried out
under solvent-free conditions. Herein, we have designed
a three-component one-step synthesis of 2,3-dihydroqui-
nazolin-4(1H)-ones under catalyst- and solvent-free
conditions.
Entry
Ar
4-BrC6H4
4-FC6H4
Product
Yields (%)
1
2
4a
4b
4c
4d
4e
4f
90
95
96
98
89
87
94
90
96
91
94
92
89
95
88
3
4
4-CH3C6H4
4-CH3OC6H4
3-ClC6H4
5
6
3-BrC6H4
7
3,4-(CH3)2C6H3
2-ClC6H4
4-ClC6H4
4g
4h
4i
8
9
10
11
12
13
14
15
C6H5
4j
4k
4l
4m
5a
5b
2,5-(CH3O)2C6H3
3,4-(CH3O)2C6H3
4-pyridyl
2-CH3OC6H4
3,4,5-(CH3O)3C6H2
RESULTS AND DISCUSSION
ity, mild reaction conditions, and improved yields are
the advantages of this new method. Moreover, the prod-
ucts were performed in excellent yields within short
reaction times. It is worth noting that the primary high-
light of this method lies in that it did not use any toxic
solvent and any catalyst in the reaction. Starting materi-
als are also inexpensive and commercially available.
We carried out the reaction of aromatic aldehyde 1,
isatoic anhydride 2, and ammonium acetate 3 in a mor-
tar (Scheme 1). The mixture was ground and then heated
at 70ꢀC under solvent-free and catalyst-free conditions
for about 10 min and the reactions could be completed,
and the corresponding 2,3-dihydroquinazolin-4(1H)-ones
were obtained in excellent yields (Table 1).
Encouraged by this success, we examined the scope
and limitations of this approach by applying the optimal
reaction conditions to a number of aromatic aldehydes
bearing electron-withdrawing and electron-donating sub-
stituents. We found that the property of substituent
groups of the aromatic aldehydes did not affect these
reactions. The results of the reaction are listed in Table 1.
In the course of our study, we found a amusing phe-
nomena: when we use 2-methoxybenzaldehyde and
3,4,5-trimethoxybenzaldehyde, we obtained the products
2-arylquin-azolin-4(3H)-one 5; however, we did not
gain corresponding products 2-aryl-2,3-dihydroquinazo-
lin-4(1H)-one 4. Although we tried many times using
the same reagents, the results were the same. The struc-
tures of all the products were confirmed on the basis of
spectroscopic data, particularly 1H-NMR analysis and
HRMS spectra.
EXPERIMENTAL
Melting points were determined on XT-5 microscopic melt-
ing point apparatus and were uncorrected. IR spectra were
1
recorded on a FTIR-8101 spectrometer. H-NMR spectra were
obtained from solution in DMSO-d6 with Me4Si as an internal
standard using a Bruker-400 spectrometer. Microanalyses were
carried out using a Perkin-Elmer 2400 II analyzer. HRMS
spectra were obtained with
instrument.
a Bruker micrOTOF-Q 134
General procedure for the synthesis of 2,3-dihydroquina-
zolin-4(1H)-one derivatives. A round-bottom flask was
charged with aromatic aldehydes 1 (2 mmol), isatoic anhydride
2 (2 mmol), and ammonium acetate 3 (3 mmol). The mixture
was heated at ꢁ70ꢀC over the course of 10 min. After the
reaction was completed, the reaction mixture was poured into
water and then washed with water thoroughly. The product
was filtered, dried, and recrystallized from 95% ethanol.
2-(4-Bromophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4a). m.p. 202–204ꢀC; IR (KBr, m, cmꢂ1): 3309, 3190, 3065,
1655, 1609, 1509, 1485, 1433, 1385, 1293, 1153, 1014, 753,
679, 668 cmꢂ1 1H-NMR (400 MHz, DMSO-d6) (d, ppm):
;
In conclusion, in this article, we have developed a
successful protocol for the efficient and facile synthesis
of 2,3-dihydroquinazolin-4(1H)-one derivatives via the
one-pot reaction under solvent-free conditions. High ef-
ficiency, easy availability, low cost, operational simplic-
5.76 (1H, s, CH), 6.69 (1H, t, J ¼ 7.2 Hz, J ¼ 7.6 Hz, ArH),
6.75 (1H, d, J ¼ 8.0 Hz, ArH), 7.16 (1H, s, NH), 7.26 (1H, t,
J ¼ 8.4 Hz, ArH), 7.44 (2H, d, J ¼ 8.4 Hz, ArH), 7.60 (3H,
d, J ¼ 8.4 Hz, ArH), 8.35 (1H, s, NH); Anal. Calcd. for
C14H11BrN2O: C, 55.47; H, 3.66; N, 9.24. Found: C, 55.40; H,
3.68; N, 9.30. HRMS m/z calculated for C14H11BrN2O
[MþNa]: 324.9952, found: 324.9947.
Scheme 1
2-(4-Fluorophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4b). m.p. 197–199ꢀC; IR (KBr, m, cmꢂ1): 3302, 3184, 3068,
1653, 1613, 1509, 1487, 1439, 1389, 1300, 1234, 1157, 842,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2011
An Efficient Synthesis of 2,3-Dihydroquinazolin-4(1H)-one Derivatives
under Catalyst-Free and Solvent-Free Conditions
959
811, 747, 670 cmꢂ1
;
1H-NMR (400 MHz, DMSO-d6) (d,
(1H, t, J ¼ 7.6 Hz, J ¼ 7.2 Hz, ArH), 7.74 (1H, d, J ¼ 8.0
Hz, ArH), 7.84 (1H, t, J ¼ 8.0 Hz, J ¼ 8.4 Hz, ArH), 7.92
(1H, d, J ¼ 7.6 Hz, ArH), 8.01 (1H, s, ArH), 8.15 (1H, d, J ¼
0.8 Hz, ArH), 8.53 (1H, s, NH); 13C-NMR (400 MHz, DMSO-
d6) (d, ppm): 163.6, 147.9, 138.9, 136.4, 135.9, 133.2, 129.3,
128.0, 127.3, 124.2, 117.0, 115.0, 114.4, 66.5, 19.4, 19.0;
Anal. Calcd. for C16H16N2O: C, 76.16; H, 6.39; N, 11.10.
Found: C, 76.32; H, 6.35; N, 11.14. HRMS m/z calculated for
C16H16N2O [MþNa]: 275.1160, found: 275.1188.
ppm): 5.78 (1H, s, CH), 6.69 (1H, t, J ¼ 7.6 Hz, J ¼ 7.2 Hz,
ArH), 6.75 (1H, d, J ¼ 8.4 Hz, ArH), 7.10 (1H, s, NH), 7.23
(3H, t, J ¼ 8.8 Hz, ArH), 7.54 (2H, dd, J ¼ 5.6 Hz, J ¼ 5.6
Hz, ArH), 7.62 (1H, d, J ¼ 7.6 Hz, ArH), 8.30 (1H, s, NH);
Anal. Calcd. for C14H11FN2O: C, 69.41; H, 4.58; N, 11.56.
Found: C, 69.50; H, 4.54; N, 11.51. HRMS m/z calculated for
C14H11FN2O [MþNa]: 265.0753, found: 265.0768.
2-p-Tolyl-2,3-dihydroquinazolin-4(1H)-one (4c). m.p. 221–
223ꢀC; IR (KBr, m, cmꢂ1): 3312, 3195, 3065, 1656, 1611,
2-(2-Chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4h). m.p. 204–206ꢀC; IR (KBr, m, cmꢂ1): 3362, 3196, 3066,
1648, 1615, 1505, 1395, 1352, 1330, 1353, 1189, 1155, 1123,
1542, 1509, 1487, 1437, 1297, 1151, 752, 669, 657 cmꢂ1; H-
1
NMR (400 MHz, DMSO-d6) (d, ppm): 2.30 (3H, s, CH3), 5.71
(1H, s, CH), 6.67 (1H, t, J ¼ 7.6 Hz, J ¼ 7.6 Hz, ArH), 6.74
(1H, d, J ¼ 8.0 Hz, ArH), 7.07 (1H, s, NH), 7.19 (2H, d, J ¼
8.0 Hz, ArH), 7.24 (1H, t, J ¼ 8.4 Hz, ArH), 7.37 (2H, d, J ¼
8.0 Hz, ArH), 7.60 (1H, d, J ¼ 7.6 Hz, ArH), 8.25 (1H, s,
NH); Anal. Calcd. for C15H14N2O: C, 75.61; H, 5.92; N,
11.76. Found: C, 75.73; H, 5.96; N, 11.70. HRMS m/z calcu-
lated for C15H14N2O [MþNa]: 261.1004, found: 261.1002.
2-(4-Methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
(4d). m.p. 189–191ꢀC; IR (KBr, m, cmꢂ1): 3300, 3185, 3053,
1654, 1613, 1509, 1488, 1438, 1390, 1305, 1255, 1033, 836,
746, 669, 618 cmꢂ1 1H-NMR (400 MHz, DMSO-d6) (d,
;
ppm): 6.14 (1H, s, CH), 6.72 (1H, t, J ¼ 7.2 Hz, J ¼ 7.6 Hz,
ArH), 6.76 (1H, d, J ¼ 8.0 Hz, ArH), 7.03 (1H, s, NH), 7.27
(1H, t, J ¼ 8.4 Hz, ArH), 7.39–7.43 (2H, m, ArH), 7.48–7.52
(1H, m, ArH), 7.66 (2H, d, J ¼ 6.0 Hz, ArH), 8.23 (1H, s,
NH); 13C-NMR (400 MHz, DMSO-d6) (d, ppm): 163.6, 147.6,
137.9,133.4, 131.8, 130.2, 129.6, 128.7, 127.4, 127.3, 117.4,
114.7, 114.5, 63.7; Anal. Calcd. for C14H11ClN2O: C, 65.00;
H, 4.29; N, 10.83. Found: C, 65.30; H, 4.32; N, 10.77. HRMS
m/z calculated for C14H11ClN2O [MþNa]: 281.0458, found:
281.0476.
2-(4-Chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4i). m.p. 197–199ꢀC; IR (KBr, m, cmꢂ1): 3309, 3188, 3066,
1655, 1611, 1509, 1486, 1386, 1293, 1153, 1093, 1017, 837,
801, 753, 669 cmꢂ1 1H-NMR (400 MHz, DMSO-d6) (d,
;
ppm): 5.77 (1H, s, CH), 6.69 (1H, t, J ¼ 7.2 Hz, J ¼ 7.6 Hz,
ArH), 6.75 (1H, d, J ¼ 8.0 Hz, ArH), 7.15 (1H, s, NH), 7.26
(1H, t, J ¼ 7.6 Hz, J ¼ 8.8 Hz, ArH), 7.49 (3H, dd, J ¼ 8.8
Hz, J ¼ 8.8 Hz, ArH), 7.62 (2H, d, J ¼ 8.8 Hz, ArH), 8.35
(1H, s, NH); Anal. Calcd. for C14H11ClN2O: C, 65.00; H,
4.29; N, 10.83. Found: C, 65.35; H, 4.25; N, 10.78. HRMS m/
z calculated for C14H11ClN2O [MþNa]: 281.0458, found:
281.0460.
806, 758, 669 cmꢂ1 1H-NMR (400 MHz, DMSO-d6) (d,
;
ppm): 3.75 (3H, s, OCH3), 5.71 (1H, s, CH), 6.68 (1H, t, J ¼
7.6 Hz, J ¼ 7.2 Hz, ArH), 6.74 (1H, d, J ¼ 8.4 Hz, ArH),
6.95 (2H, d, J ¼ 8.8 Hz, ArH), 7.01 (1H, s, NH), 7.24 (1H, t,
J ¼ 8.4 Hz, ArH), 7.42 (2H, d, J ¼ 8.8 Hz, ArH), 7.61 (1H,
dd, J ¼ 1.2 Hz, J ¼ 1.2 Hz, ArH), 8.19 (1H, s, NH); Anal.
Calcd. for C15H14N2O2: C, 70.85; H, 5.55; N, 11.02. Found:
C, 70.67; H, 5.57; N, 11.05. HRMS m/z calculated for
C15H14N2O2 [MþNa]: 277.0953, found: 277.0969.
2-(3-Chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4e). m.p. 185–186ꢀC; IR (KBr, m, cmꢂ1): 3291, 3198, 3067,
1650, 1614, 1514, 1487, 1436, 1387, 1340, 1299, 1201, 1157,
871, 818, 793, 756, 699, 667 cmꢂ1 1H-NMR (400 MHz,
;
2-Phenyl-2,3-dihydroquinazolin-4(1H)-one (4j). m.p. 223–
224ꢀC; IR (KBr, m, cmꢂ1): 3304, 3188, 1668, 1652, 1615,
DMSO-d6) (d, ppm): 5.78 (1H, s, CH), 6.69 (1H, t, J ¼ 7.6
Hz, J ¼ 7.2 Hz, ArH), 6.76 (1H, d, J ¼ 8.0 Hz, ArH), 7.22
(1H, s, ArH), 7.26 (1H, t, J ¼ 8.4 Hz, ArH), 7.42 (3H, m,
ArH), 7.53 (1H, s, NH), 7.61 (1H, dd, J ¼ 1.2 Hz, J ¼ 1.2
Hz, ArH), 8.40 (1H, s, NH); Anal. Calcd. for C14H11ClN2O:
C, 65.00; H, 4.29; N, 10.83. Found: C, 65.35; H, 4.33; N,
10.79. HRMS m/z calculated for C14H11ClN2O [MþNa]:
281.0458, found: 281.0482.
2-(3-Bromophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4f). m.p. 179–181ꢀC; IR (KBr, m, cmꢂ1): 3271, 3182, 3057,
1650, 1615, 1509, 1433, 1389, 1298, 1264, 1150, 888, 752,
698, 613 cmꢂ1 1H-NMR (400 MHz, DMSO-d6) (d, ppm):
;
1507, 1487, 1455, 1393, 1300, 1149, 748, 699, 667, 643 cmꢂ1
;
1H-NMR (400 MHz, DMSO-d6) (d, ppm): 5.76 (1H, s, CH),
6.68 (1H, t, J ¼ 7.2 Hz, ArH), 6.75 (1H, d, J ¼ 8.0 Hz, ArH),
7.14 (1H, s, NH), 7.25 (1H, t, J ¼ 8.4 Hz, ArH), 7.35–7.42
(3H, m, ArH), 7.50 (2H, d, J ¼ 6.8 Hz, ArH), 7.62 (1H, dd, J
¼ 1.2 Hz, J ¼ 1.2 Hz, ArH), 8.32 (1H, s, NH); Anal. Calcd.
for C14H12N2O: C, 74.98; H, 5.39; N, 12.49. Found: C, 74.70;
H, 5.41; N, 12.43. HRMS m/z calculated for C14H12N2O
[MþNa]: 247.0847, found: 247.0843.
2-(2,5-Dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
(4k). m.p. 164–165ꢀC; IR (KBr, m, cmꢂ1): 3198, 3102, 1651,
1610, 1577, 1498, 1457, 1357, 1310, 1282, 1250, 1220, 1122,
5.67 (1H, s, CH), 6.69 (1H, t, J ¼ 7.6 Hz, J ¼ 7.2 Hz, ArH),
6.76 (1H, d, J ¼ 8.0 Hz, ArH), 7.23 (1H, s, ArH), 7.26 (1H, t,
J ¼ 8.4 Hz, ArH), 7.36 (1H, t, J ¼ 7.6 Hz, J ¼ 8.0 Hz, ArH),
7.49 (1H, d, J ¼ 7.6 Hz, ArH), 7.54 (1H, d, J ¼ 9.2 Hz, ArH),
7.61 (1H, d, J ¼ 1.2 Hz, ArH), 7.67 (1H, s, NH), 8.52 (1H, s,
NH); Anal. Calcd. for C14H11BrN2O: C, 55.47; H, 3.66; N,
9.24. Found: C, 55.53; H, 3.63; N, 9.19. HRMS m/z calculated
for C14H11BrN2O [MþNa]: 324.9952, found: 324.9945.
1051, 759, 702 cmꢂ1 1H-NMR (400 MHz, DMSO-d6) (d,
;
ppm): 3.67 (3H, s, OCH3), 3.79 (3H, s, OCH3), 5.99 (1H, s,
CH), 6.68 (1H, t, J ¼ 7.2 Hz, J ¼ 7.6 Hz, ArH), 6.78 (1H, d,
J ¼ 8.0 Hz, ArH), 6.82 (1H, s, NH), 6.89 (1H, dd, J ¼ 3.2
Hz, J ¼ 3.2 Hz, ArH), 6.95–7.00 (2H, m, ArH), 7.24 (1H, t, J
¼ 7.2 Hz, J ¼ 7.6 Hz, ArH), 7.63 (1H, d, J ¼ 7.6 Hz, ArH),
8.06 (1H, s, NH); 13C-NMR (400 MHz, DMSO-d6) (d, ppm):
163.8, 152.9, 150.5, 147.9, 133.2, 129.9, 127.3, 117.1, 114.8,
114.5, 113.5, 113.4, 112.2, 61.0, 56.0, 55.4; Anal. Calcd. for
C16H16N2O3: C, 67.59; H, 5.67; N, 9.85. Found: C, 67.50; H,
5.62; N, 9.89. HRMS m/z calculated for C16H16N2O3 [MþNa]:
307.1059, found: 307.1061.
2-(3,4-Dimethylphenyl)-2,3-dihydroquinazolin-4(1H)-one
(4g). m.p. 186–188ꢀC; IR (KBr, m, cmꢂ1): 3294, 3193, 3068,
1651, 1615, 1516, 1488, 1447, 1386, 1334, 1299, 1152, 1132,
829, 808, 755, 657, 624 cmꢂ1 1H-NMR (400 MHz, DMSO-
;
d6) (d, ppm): 2.30 (3H, s, CH3), 2.32 (3H, s, CH3), 5.67 (1H,
s, CH), 7.11 (1H, s, NH), 7.31 (1H, d, J ¼ 8.0 Hz, ArH), 7.51
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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L. Gao, H. Ji, L. Rong, D. Tang, Y. Zha, Y. Shi, and S. Tu
Vol 48
calculated for C17H16N2O4 [MþNa]: 335.1008, found:
2-(3,4-Dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
(4l). m.p. 208–210ꢀC; IR (KBr, m, cmꢂ1): 3354, 3333, 1671,
1609, 1557, 1539, 1516, 1496, 1480, 1456, 1415, 1363, 1318,
335.1005.
1269, 1227, 1144, 1015, 854, 769, 702 cmꢂ1 1H-NMR (400
;
Acknowledgments. The authors are grateful to the Natural Sci-
ence Foundation of Jiangsu Education Department (No.
08KJB150017), the Pei Yu Foundation (No. 07PYL06) of Xuz-
hou Normal University, and the Qing Lan Project
(NO.08QLT001) for financial support.
MHz, DMSO-d6) (d, ppm): 3.58 (3H, s, OCH3), 3.60 (3H, s,
OCH3), 5.54 (1H, s, CH), 6.52 (1H, t, J ¼ 7.2 Hz, J ¼ 7.6
Hz, ArH), 6.60 (1H, d, J ¼ 8.0 Hz, ArH), 6.79 (1H, d, J ¼
8.4 Hz, ArH), 6.85 (1H, d, J ¼ 8.0 Hz, ArH), 6.88 (1H, s,
NH), 6.97 (1H, s, ArH), 7.09 (1H, t, J ¼ 8.4 Hz, J ¼ 8.4 Hz,
ArH), 7.46 (1H, dd, J ¼ 1.2 Hz, J ¼ 1.2 Hz, ArH), 8.05 (1H,
s, NH); Anal. Calcd. for C16H16N2O3: C, 67.59; H, 5.67; N,
9.85. Found: C, 67.61; H, 5.70; N, 9.91. HRMS m/z calculated
for C16H16N2O3 [MþNa]: 307.1059, found: 307.1059.
REFERENCES AND NOTES
[1] Dou, G. L.; Shi, D. Q.; Li, Y. H. J Comb Chem 2010, 12, 195.
[2] (a) Hamel, E.; Lin, C. M.; Plowman, J.; Wang, H.; Lee, K.;
Paull, K. D. Biochem Pharmacol 1996, 51, 53; (b) Biressi, M. G.;
Cantarelli, G.; Carissimi, M.; Cattaneo, A.; Ravenna, F. Farmaco Ed
Sci 1969, 24, 199; (c) Bhalla, P. R.; Walworth, B. L. American Cyana-
mid Co. Eur. Pat. Appl. EP58.822 (1982); (c) Bhalla, P. R.; Walworth,
B. L. Chem. Abstr. 1983, 98, 1669; (d) Bhalla, P. R.; Walworth, B. L.
American Cyanamid Co. U.S. Pat. 4,431,440 (1984); (d) Bhalla, P. R.;
Walworth, B. L. Chem. Abstr. 1984, 100, 174857; (e) Hour, M.;
Huang, L.; Kuo, S.; Xia, Y.; Bastow, K.; Nakanishi, Y.; Hamel, E.;
Lee, K. J Med Chem 2000, 43, 4479.
2-(Pyridin-4-yl)-2,3-dihydroquinazolin-4(1H)-one (4m). m.p.
264–265ꢀC; IR (KBr, m, cmꢂ1): 3207, 2957, 1678, 1648, 1599,
1570, 1559, 1489, 1468, 1449, 1304, 1189, 772, 699 cmꢂ1
;
1H-NMR (400 MHz, DMSO-d6) (d, ppm): 7.53–7.63 (2H, m,
ArH, CH), 7.80 (1H, d, J ¼ 8.0 Hz, ArH), 7.89 (1H, t, J ¼
7.2 Hz, J ¼ 7.6 Hz, CH), 8.12 (2H, d, J ¼ 6.0 Hz, ArH), 8.19
(1H, d, J ¼ 7.6 Hz, NH), 8.72 (1H, s, NH), 8.80 (2H, d, J ¼
5.6 Hz, ArH), 12.81 (1H, s, NH); Anal. Calcd. for C13H11N3O:
C, 69.32; H, 4.92; N, 18.66; O, 7.10. Found: C, 69.46; H,
4.89; N, 18.69. HRMS m/z calculated for C13H11N3O
[MþNa]: 248.0800, found: 248.0802.
[3] (a) Moore, J. A.; Sutherland, G. J.; Sowerby, R.; Kelly, E.
G.; Palermo, S.; Webdter, W. J Org Chem 1969, 34, 887; (b) Sharma,
S. D.; Kaur, V. Synthesis 1989, 677.
2-(2-Methoxyphenyl)quinazolin-4(3H)-one (5a). m.p. 202–
203ꢀC; IR (KBr, m, cmꢂ1): 3321, 3095, 1681, 1592, 1558,
[4] Yoo, C. L.; Fettinger, J. C.; Kurth, M. J. J Org Chem 2005,
70, 6941.
1478, 1456, 1302, 1235, 1186, 1138, 1016, 759, 744 cmꢂ1
;
1H-NMR (400 MHz, DMSO-d6) (d, ppm): 3.86 (3H, s, OCH3),
7.10 (1H, t, J ¼ 7.6 Hz, ArH), 7.20 (1H, d, J ¼ 8.4 Hz, ArH),
7.54 (2H, t, J ¼ 6.8 Hz, ArH), 7.71 (2H, d, J ¼ 8.0 Hz, ArH),
7.84 (1H, t, J ¼ 7.6 Hz, ArH), 8.16 (1H, d, J ¼ 7.6 Hz, ArH),
12.14 (1H, s, NH); 13C-NMR (400 MHz, DMSO-d6) (d, ppm):
163.8, 156.4, 147.9, 133.2, 129.6, 129.0, 127.3, 126.8, 120.1,
116.9, 114.7, 114.5, 111.1, 61.0, 55.5; Anal. Calcd. for
C15H12N2O2: C, 71.42; H, 4.79; N, 11.10. Found: C, 71.51; H,
4.73; N, 11.14. HRMS m/z calculated for C15H12N2O2
[MþNa]: 275.0796, found: 275.0798.
[5] Chen, J. X.; Wu, D. Z.; He, F.; Liu, M. C.; Wu, H. Y.;
Ding, J. C.; Su, W. K. Tetrahedron Lett 2008, 49, 3817.
[6] (a) Baghbanzadeh, M.; Salehi, P.; Dabiri, M.; Kozehgarya,
G. Synthesis 2006, 344; (b) Salehi, P.; Dabiri, M.; Zolfigol, M. A.;
Baghbanzadeh, M. Synlett 2005, 1155; (c) Dabiri, M.; Salehi, P.; Oto-
kesh, S.; Baghbanzadeh, M.; Kozehgarya, G.; Mohammadi, A. A. Tet-
rahedron Lett 2005, 46, 6123; (d) Salehi, P.; Dabiri, M.;
Baghbanzadeh, M.; Bahramnejad, M. Synth Commun 2006, 36, 2287.
[7] Rostamizadeh, S.; Amani, A. M.; Aryan, R.; Ghaieni, H.
R.; Shadjou, N. Synth Commun 2008, 38, 3569.
[8] Shi, D. Q.; Rong, L. C.; Wang, J. X.; Zhuang, Q. Y.;
Wang, X. S.; Hu, H. W. Tetrahedron Lett 2003, 44, 3199.
[9] Abdel-Jalil, R. J.; Voelter, W.; Saeed, M. Tetrahedron Lett
2004, 45, 3475.
2-(3,4,5-Trimethoxyphenyl)quinazolin-4(3H)-one (5b). m.p.
254–256ꢀC; IR (KBr, m, cmꢂ1): 3202, 2936, 1669, 1605, 1574,
1521, 1482, 1457, 1342, 1284, 1235, 1140, 999, 857, 840,
774, 722 cmꢂ1 1H-NMR (400 MHz, DMSO-d6) (d, ppm):
;
[10] Shaabani, A.; Maleki, A.; Mofakham, H. Synth Commun
2008, 38, 3752.
3.75 (3H, s, OCH3), 3.91 (6H, s, 2ꢃOCH3), 7.53 (1H, t, J ¼
7.6 Hz, J ¼ 7.2 Hz, ArH), 7.57 (2H, s, ArH), 7.76 (1H, d, J ¼
8.0 Hz, ArH), 7.85 (1H, t, J ¼ 7.6 Hz, J ¼ 8.4 Hz, ArH), 8.16
(1H, d, J ¼ 7.6 Hz, ArH), 12.56 (1H, s, NH); 13C-NMR (400
MHz, DMSO-d6) (d, ppm): 162.2, 158.5, 158.1, 152.9, 152.0,
148.1, 140.4, 134.7, 127.3, 127.0, 126.5, 125.9, 120.7, 113.7,
105.4, 60.2, 56.2; Anal. Calcd. for C17H16N2O4: C, 65.38; H,
5.16; N, 8.97. Found: C, 65.55; H, 5.20; N, 8.92. HRMS m/z
[11] Chen, J. X.; Wu, H. Y.; Su, W. K. Chin Chem Lett 2007,
18, 537.
[12] Su, W. K.; Yang, B. B. Aust J Chem 2002, 55, 695.
[13] (a) Pandey, G.; Singh, R. P.; Gary, A.; Singh, V. K. Tetra-
hedron Lett 2005, 46, 2137; (b) Werner, B.; Domling, A. Molecules
2003, 8, 53; (c) Domling, A.; Ugi, I. Angew Chem Int Ed 2000, 39,
3169; (d) Kappe, C. O. Acc Chem Res 2000, 33, 879.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet