One-pot synthesis of 2,3-disubstituted-2,3-dihydroquinazolin-4(1H)-ones using [Hmim][NO3]: An eco-friendly protocol

Article abstract of DOI:10.1002/jhet.721

An efficient method for the synthesis of a series of 2,3-disubstituted-2,3- dihydroquinazolin-4(1H)-ones is described via one-pot condensation reaction of isatoic anhydride, aryl aldehydes, and primary amines using a Bronsted acidic ionic liquid, [Hmim][N

Full text of DOI:10.1002/jhet.721

November 2011
One-Pot Synthesis of 2,3-Disubstituted-2,3-dihydroquinazolin-
4(1H)-ones Using [Hmim][NO3]: An Eco-Friendly Protocol
1419
Iraj Mohammadpoor-Baltork,* Ahmad Reza Khosropour,* Majid Moghadam,
Shahram Tangestaninejad, Valiollah Mirkhani,
Mohammad Soltani, and Arsalan Mirjafari
Catalysis Division, Department of Chemistry, University of Isfahan, Isfahan 81746-7344, Iran
*E-mail: imbaltork@sci.ui.ac.ir or khosropour@sci.ui.ac.ir
Received July 16, 2010
DOI 10.1002/jhet.721
Published online 19 August 2011 in Wiley Online Library (wileyonlinelibrary.com).
An efficient method for the synthesis of a series of 2,3-disubstituted-2,3-dihydroquinazolin-4(1H)-
ones is described via one-pot condensation reaction of isatoic anhydride, aryl aldehydes, and primary
amines using a Brønsted acidic ionic liquid, [Hmim][NO3], as a catalyst and medium. The present pro-
tocol enjoys convenient reaction and simple work-up, greenness, short reaction times, and reusable cata-
lyst as well as mild reaction conditions.
J. Heterocyclic Chem., 48, 1419 (2011).
INTRODUCTION
[12], and methaqualone II which has antimalarial effect
and currently being used for the assessment of the abuse
liability of sedative hypnotic drugs [13] (Scheme 1).
Although there are several reports on the synthesis 2,3-
disubstuted-2,3-dihydroquinazoline-4(1H)-one derivatives,
[14,15] yet the investigations for a convenient and green
synthesis is on due to different drawbacks in the existing
methods, e.g., harsh reaction conditions, using toxic sol-
vents and metal-based catalysts, low yield, time consum-
ing, and no easy available precursors. Chen et al. [16] has
reported a new method for the preparation of 2,3-dihydro-
quinazoline-4(1H)-ones using classic ionic liquids such as
[Cnmim][PF6] or [Cnmim][BF4] (n ¼ 2 and 4). The main
disadvantage of this method is instability of [PF6]ꢀ and
[BF4]ꢀ anions toward hydrolysis in contact with moisture,
forming HF and POF3, which can dissolve glassware and
damage steel autoclaves and reactors [17].
The recent interest surrounding ionic liquids in
regards to green chemistry and the associated develop-
ment in their versatile applications has largely been a
result of their unique physicochemical properties [1].
Significant research efforts ensued when ILs emerged as
a possible ‘‘green’’ alternative to common organic sol-
vents. In this decade, investigations have commenced to
finding specialized technological applications for ILs
such as catalysis and biocatalysis [2], energetic materials
[3], polymer plasticizers [4], lubricants [5], cellulose
dissolution [6], and active pharmaceutical ingredients
(APIs) [7]. Recently, ILs continuing to shift from the
research laboratory to industries [8].
Quinazolinones are commonly used substructure
within the pharmaceutical industry, as these fused hetero-
cycles impart unique physical and biological compounds
of interest. It occurs in different natural products and in a
variety of synthetic compounds [9]. 2,3-Disubstuted-2,3-
dihydroquinazoline-4(1H)-one alkaloids are a class of nat-
ural products which exhibit a variety of pharmaceutical
activity [10] include anti-inflammatory, antibacterial, anti-
microbial, antidepressant, and anticancer [11]. Known
2,3-disubstuted-2,3-dihydroquinazoline-4(1H)-one drugs
are diproqualone I which is used primarily for the treat-
ment of inflammatory pain associated with osteoarthritis
Our recent interest has been in the development of green
synthetic methods on using ILs for the preparation of qui-
nazolin-4(3H)-ones [18]. Herein, we report a highly effi-
cient, one-pot, three-component, and eco-friendly protocol
for the synthesis of 2,3-disubstuted-2,3-dihydroquinazoline-
4(1H)-one derivatives 4 by the condensation reaction of
isatoic anhydride 1, aryl aldehydes 2, and primary amines
3 using 1-methylimidazolium nitrate, [Hmim][NO3], as a
catalyst and medium at thermal conditions (Scheme 2).
To the best of our knowledge in the open literature, this
C
V
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I. Mohammadpoor-Baltork, A. R. Khosropour, M. Moghadam, S. Tangestaninejad,
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Vol 48
Scheme 1. Structure of 2,3-disubstuted-2,3-dihydroquinazoline-4(1H)-
one drugs, diproqualone (I) and methaqualone (II).
derivatives in excellent yields (Table 3). On the other
hand, aliphatic aldehydes as well as unsaturated ones,
showed very poor yields. Another important aspect is that
various functionalities such as methoxy, nitrile, halides,
nitro, etc., were survived under the present reaction condi-
tions (Table 3). The reaction conditions are mild enough
not to damage to moieties such as methoxy which often
undergoes cleavage in the strong acidic media (Table 3,
entries 8, 9, 17, and 21). To evaluate the generality of this
method, we also concentrated our study on the different
primary amines (Table 3). The results illustrate the high
ability of this method for synthesis of 2,3-disubstuted-2,3-
dihydroquinazoline-4(1H)-ones with varied structures.
Chaiappe et al. reported [Hmim][NO3] used as a pro-
moter-solvent in the oxidative aromatic chlorination
[19]. During our own investigation, no evidence was
obtained to show the oxidation reaction for all of the
2,3-disubstuted-2,3-dihydroquinazoline-4(1H)-one prod-
ucts was occurred under this reaction conditions.
reaction involving a hydrophilic task-specific ionic liq-
uid (TSIL) is unprecedented.
RESULTS AND DISCUSSION
The experimental procedure for this reaction is
remarkably simple and requires no toxic organic sol-
vents or inert atmosphere. The best results for this con-
densation reaction were obtained by taking a 1.1:1:1
mol ratio mixture of isatoic anhydride, aromatic alde-
hyde, and primary amine using 1 mmol [Hmim][NO3]
(Table 1) at thermal conditions (80ꢁC) for 1–2 h. The
reaction proceeded fast with high yield of the desired
products using a Brønsted acidic ionic liquid (BAIL)
with dual roles of catalyst and medium.
Because of the need to explore the role of water in
this process, a study was performed which focused on
the effect of water content of ionic liquid on its catalytic
activity. The data listed in Table 4 were illustrated that
catalytic activity of [Hmim][NO3] heavily dependent of
the amount of water content. That is, the ratio of water
to ionic liquid must ranging between 0% and 15% (w/
w) to obtain optimum yield (Table 4, entries 1 and 2).
Furthermore, the ionic liquid [Hmim][NO3] was misci-
ble with water, whereas the products were immiscible
with the ionic liquid; therefore, the water produced in
the condensation reactions did not need to be removed.
The reusability of catalyst is important from an envi-
ronmental point of view and economic consideration.
Therefore, reusability of this ionic liquid was also exam-
ined using sequential reactions. The obtained results
indicated that the catalyst could be recovered and reused
successfully for four times without remarkable decrease
in the product yield (82–94%).
In an initial study, to examine the catalytic activity of dif-
ferent Brønsted acidic ionic liquids such as [Hmim][Cl],
[Hmim][HSO4], and [Hmim][NO3] in this condensation
reaction, 4-chlorobenzyladehede was first reacted with isa-
toic anhydride and ethylamine using each ionic liquids sepa-
rately, at thermal conditions. These Brønsted acidic ionic
liquids can be prepared simply by neutralization. In the
course of this study, we found that [Hmim][NO3] was
the most effective catalyst in the term of yield of corre-
sponding 2-ethyl-3-aryl-2,3-dihydroquinazoline-4(1H)-one
(94%); whereas other ionic liquids formed the product with
the yield of 63–86% (Table 2). In the absence of IL, the yield
of product was found to be extremely low (Table 2, entry 4).
The generality of this process was demonstrated by the
wide range of substituted and structurally diverse aryl alde-
hydes carrying either electron-withdrawing or electron-
donating groups, which were used to synthesize the corre-
sponding 2,3-disubstuted-2,3-dihydroquinazoline-4(1H)-one
CONCLUSIONS
In conclusion, [Hmim][NO3] can be considered as a
promising alternative medium and catalyst for the
Scheme 2. Synthesis of 2,3-disubstituted-2,3-dihydroquinazolin-4(1H)-ones using [Hmim][NO3] as a catalyst and medium.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2011
One-Pot Synthesis of 2,3-Disubstituted-2,3-dihydroquinazolin-4(1H)-ones
Using [Hmim][NO3]: An Eco-Friendly Protocol
1421
Table 1
gresses of reactions were monitored by TLC (ethyl acetate: n-
hexane, 1:3). After completion of reaction, 10-mL ethyl acetate
(EtOAc) was added to the flask and completely was stirred.
Then the solution was transferred to the funnel. The 2,3-disub-
Reaction of isatoic anhydride, 4-chlorobenzaldehyde, and ethylamine
using different amounts of [Hmim][NO3].a
stituted-2,3-dihydroquinazolin-4(1H)-one
products
were
extracted by EtOAc, the organic layer was separated, and the
solvent was evaporated under vacuum. The product was puri-
fied by recrystallization of residue from n-hexane.
[Hmim][NO3] recovery and reuse. The reusability of
[Hmim][NO3] was investigated in the multiple sequential reac-
tion of isatoic anhydride, 4-chlorobenzaldehyde, and ethyla-
mine. At the end of the reaction, IL was separated from the
reaction mixture by extraction of the organics by ethyl acetate
(2 ꢂ 10 mL). The aqueous phase containing IL was dried in
vacuo for further use. Recycling was done until minimum
yields up to 80% are obtained.
Entry
Ionic liquid (mmol)
Yield (%)b
1
2
3
4
0.8
0.9
1
75
86
94
94
1.1
a Reaction conditions: isatoic anhydride (1.1 mmol), ethylamine (1
mmol), 4-chlorobenzaldehyde (1 mmol), IL (1 mmol).
b Isolated yield.
Spectral data.
2-(4-Chlorophenyl)-3-ethyl-2,3-dihydro-
quinazolin-4(1H)-one (4a). (94%), mp 132–135ꢁC; IR (KBr)
tmax ¼ 3227, 3028, 2030, 1630, 1576, 1524, 1472, 1319,
1219, 1088, 1014, 844, 744 cmꢀ1 1H-NMR (500 MHz,
;
synthesis of 2,3-disubstuted-2,3-dihydroquinazoline-4(1H)-
ones, starting from isatoic anhydride, aryl aldehydes, and
primary amines. This IL is non-volatile, air stable, easy to
prepare and handle, and reusable. It also can act as an
environmentally friendly catalytic system for this transfor-
mation showed that rate of reactions were enhanced and
products were obtained in excellent yield. Moreover, this
research not only affords the products in high yields but
also avoids the problems associated with catalyst cost,
non-green reaction conditions, safety, and pollution.
CDCl3): dH 1.60 (t, J ¼ 7.2 Hz, 3H, CH3), 2.93–2.97 (m, 1H,
NCH2CH3), 3.93–3.97 (m, 1H, NCH2CH3), 4.55 (br, s, 1H,
NH), 5.78 (s, 1H, CH), 6.56 (d, J ¼ 7.9 Hz, 1H, ArH), 6.89
(td, J1 ¼ 7.6 Hz, J2 ¼ 0.9 Hz, 1H, ArH), 7.26–7.30 (m, 1H,
ArH), 7.34–7.38 (m, 4H, ArH), 7.99 (dd, J1 ¼ 7.8 Hz, J2
¼
1.5 Hz, 1H, ArH).
2-(2,4-Dichlorophenyl)-3-ethyl-2,3-dihydroquinazolin-4(1H)-
one (4b). (97%), mp 158–161ꢁC; IR (KBr): 3248, 2990, 1628,
1512, 1475, 1421, 1321, 1254, 1217, 1155, 1103, 1043, 847,
;
754, 698, 613, 527 cmꢀ1 1H-NMR (500 MHz, CDCl3): dH
1.25 (t, J ¼ 7.2 Hz, 3H, CH3), 2.85–2.92 (m, 1H, NCH2CH3),
4.08–4.14 (m, 1H, NCH2CH3), 5.09 (br, s, 1H, NH), 6.10 (d, J
¼ 2.4 Hz, 1H, CH), 6.53 (d, J ¼ 8.0 Hz, 1H, ArH), 6.84 (t, J
¼ 7.7 Hz, 1H, ArH), 7.16–7.18 (m, 1H, ArH), 7.21–7.25 (m,
2H, ArH), 7.43 (d, J ¼ 2.0 Hz, 1H, ArH), 7.96 (dd, J1 ¼ 7.4
Hz, J2 ¼ 0.8 Hz, 1H, ArH); 13C-NMR (125 MHz, CDCl3): d
13.6, 40.6, 67.9, 115.0, 116.4, 120.0, 128.0, 128.7, 128.8,
130.5, 133.0, 134.0, 135.7, 135.9, 144.6, 163.5 ppm; MS (EI,
70 eV): m/z ¼ 321 (Mþ, 5), 320 (M ꢀ 1, 3), 175 (86), 147
(76), 75 (100); Anal. Calcd. for C16H14Cl2N2O: C, 59.83; H,
4.39; N, 8.72; Found: C, 59.97; H, 4.34; N, 8.56.
EXPERIMENTAL
Melting points were obtained by Stuart Scientific SMP2 ap-
paratus and are uncorrected. Yields refer to isolated products
and all products were characterized by their physical and spec-
tral data. IR spectra were recorded on FTIR NICO let 400D.
1H- and 13C-NMR (500 and 125 MHz) spectra were recorded
on a Bruker-Avance AQS 500 spectrometer in CDCl3. Mass
spectra were obtained on platform II spectrometer from Micro
mass; EI mode at 70 eV. Elemental analysis was done on
LECO, CHNS-932.
Table 2
Synthesis of 1-methylimidazolium nitrate, [Hmim]
[NO3]. A dilute nitric acid solution [5.059 g of nitric acid (65
wt %) in 20-mL water] was added to an aqueous solution of
1.05 equiv of N-methylimidazol (4.089 g, 49.79 mmol) at 0ꢁC.
The reaction mixture was allowed to warm to room tempera-
ture. Water was removed by sweeping compressed air above
the solution at 80ꢁC. Upon cooling the liquid down to room
temperature, a white solid formed. This was powdered, washed
with diethyl ether, and dried in vacuo at 40ꢁC. IL was decolor-
ized by refluxing the aqueous solution in the presence of char-
coal for 24 h. Then, mixture was filtrate and water of filtrate
was removed in vacuo for 12 h.
General procedure for the synthesis of 2,3-dihydroquina-
zolin-4(1H)-ones. Isatoic anhydride (1.1 mmol), aryl aldehyde
(1 mmol), and primary amine (1 mmol) were successively
added to [Hmim][NO3] as a catalyst-medium (1 mmol) in a
25-mL flask. The mixture was heated under vigorously stirring
at 80ꢁC for appropriate times according to Table 3. The pro-
Reaction of isatoic anhydride, 4-chlorobenzaldehyde, and ethylamine
using catalytic activity of different brønsted acidic ionic liquids.a
Entry
BAILs
Yield (%)b
1
2
3
4
[Hmim][NO3]
[Hmim][HSO4]
[Hmim][Cl]
–
94
86
63
Trace
a Reaction conditions: isatoic anhydride (1.1 mmol), ethylamine
(1 mmol), 4-chlorobenzaldehyde (1 mmol), BAIL (1 mmol).
b Isolated yield.
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Vol 48
Table 3
Synthesis of 2,3-disubstituted-2,3-dihydroquinazolin-4(1H)-ones by condensation reaction of isatoic anhydride, aryl aldehydes, and primary amines
using [Hmim][NO3] as a catalyst-medium.a
Entry
1
Aldehyde
Amine
EtNH2
Product
Time (min)
60
Yield (%)b
94
Mp (ꢁC)
4a
132–135 [20]
2
EtNH2
EtNH2
EtNH2
EtNH2
EtNH2
EtNH2
EtNH2
EtNH2
EtNH2
4b
4c
4d
4e
4f
60
80
97
96
93
95
91
92
90
94
87
158–161
129–131
3
4
90
160–161 [20]
176–178 [20]
155–158
5
90
6
120
100
90
7
4g
4h
4i
170–172
8
112–116
9
60
146–149
10
4j
90
140–143
(Continued)
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One-Pot Synthesis of 2,3-Disubstituted-2,3-dihydroquinazolin-4(1H)-ones
Using [Hmim][NO3]: An Eco-Friendly Protocol
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Table 3
(Continued)
Entry
11
Aldehyde
Amine
EtNH2
Product
Time (min)
Yield (%)b
Mp (ꢁC)
126–128
4k
4l
60
91
12
13
14
15
16
17
18
19
20
EtNH2
n-BuNH2
n-BuNH2
n-BuNH2
n-BuNH2
n-BuNH2
n-BuNH2
n-BuNH2
PhCH2NH2
60
60
60
60
60
60
60
60
60
95
93
97
90
94
90
87
90
85
132–134
146–149
4m
4n
4o
4p
4q
4r
4s
150–151 [21]
135–138
137–139
102–105
144–146
99–101
4t
157–159
(Continued)
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Vol 48
Table 3
(Continued)
Entry
Aldehyde
Amine
Product
Time (min)
90
Yield (%)b
91
Mp (ꢁC)
21
PhCH2NH2
4u
169–171
22
23
PhCH2NH2
4v
100
100
87
88
190–193
175–177
PhCH2NH2
4w
a Reaction conditions: isatoic anhydride (1.1 mmol), aldehyde (1 mmol), amine (1 mmol), [Hmim][NO3] (1 mmol).
b Isolated yield.
1H, ArH), 8.01 (dt, J ¼ 8.2, 1.2 Hz, 1H, ArH), 8.19 (d, J ¼
2-(4-Bromophenyl)-3-ethyl-2,3-dihydroquinazolin-4(1H)-one
(4c). (96%), mp 129–131ꢁC; IR (KBr) tmax ¼ 3231, 3026,
2928, 1624, 1522, 1470, 1402, 1317, 1219, 1151, 1072, 1011,
1.6 Hz, 1H, ArH) ppm.
3-Ethyl-2-(2-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4f). (91%), mp 155–158ꢁC; IR (KBr) tmax ¼ 3308, 1626,
1
843, 743, 698 cmꢀ1; H-NMR (500 MHz, CDCl3): dH 1.16 (t,
1
1506, 1422, 1348, 1171, 754, 704 cmꢀ1; H-NMR (500 MHz,
J ¼ 7.2 Hz, 3H, CH3), 2.92–2.99 (m, 1H, NCH2CH3), 3.92–
3.99 (m, 1H, NCH2CH3), 4.60 (br, s, 1H, NH), 5.76 (s, 1H,
CH), 6.56 (d, J ¼ 7.9 Hz, 1H, ArH), 6.89 (td, J1 ¼ 7.6 Hz,
J2 ¼ 0.9 Hz, 1H, ArH), 7.26–7.34 (m, 3H, ArH), 7.50–7.52
(m, 2H, ArH), 7.98 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.5 Hz, 1H, ArH)
ppm; 13C-NMR (125 MHz, CDCl3): d 13.3, 40.0, 71.8, 114.8,
116.7, 120.0, 123.8, 128.7, 128.9, 132.6, 133.9, 139.5, 145.1,
163.2 ppm; MS (EI, 70 eV): m/z ¼ 331 (Mþ, 2), 301 (M ꢀ 1,
3), 169 (12), 61 (100); Anal. Calcd. for C16H15BrN2O: C,
58.02; H, 4.56; N, 8.46; Found: C, 57.98; H, 4.61; N, 8.42.
CDCl3): d 1.24 (t, J ¼ 7.2 Hz, 3H, CH3), 2.76–2.83 (m, 1H,
NCH2CH3), 4.12–4.19 (m, 1H, NCH2CH3), 5.42 (br, s, 1H,
NH), 6.36 (s, 1H, CH), 6.52 (d, J ¼ 7.9 Hz, 1H, ArH), 6.84
(td, J1 ¼ 7.6 Hz, J2 ¼ 0.9 Hz, 1H, ArH), 7.22–7.26 (m, 1H,
ArH), 7.47–7.53 (m, 2H, ArH), 7.57–7.60 (m, 1H, ArH), 7.98
(dd, J1 ¼ 7.8 Hz, J2 ¼ 1.4 Hz, 1H, ArH), 8.13 (dd, J1
¼
8.0 Hz, J2 ¼ 1.2 Hz, 1H, ArH) ppm; 13C-NMR (125 MHz,
CDCl3): d 13.5, 41.0, 67.3, 115.1, 115.9, 119.7, 126.4, 128.4,
128.8, 130.2, 134.1, 134.8, 136.0, 144.3, 148.0, 163.7 ppm;
MS (EI, 70 eV): m/z ¼ 297 (Mþ, 5), 250 (5), 175 (84), 147
(32), 91 (82), 77 (74), 76 (100).
3-Ethyl-2-(4-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4d). (93%), mp 160–161ꢁC; IR (KBr) tmax ¼ 3240, 2350,
1626, 1580, 1526, 1470, 1348, 1259, 1111, 858, 748 cmꢀ1
;
2-(4-Cyanophenyl)-3-ethyl-2,3-dihydroquinazolin4(1H)-one
(4g). (92%), mp 170–172ꢁC; IR (KBr) tmax ¼ 3235, 3053,
2928, 2254, 1624, 1520, 1472, 1408, 1317, 1258, 1221, 1167,
;
1111, 1061, 1016, 922, 862, 824, 752, 721 cmꢀ1 1H-NMR
1H-NMR (500 MHz, CDCl3): dH 1.20 (t, J ¼ 7.5 Hz, 3H,
CH3), 2.96–3.00 (m, 1H, NCH2CH3), 4.04–4.08 (m, 1H,
NCH2CH3), 4.66 (br, s, 1H, NH), 5.88 (s, 1H, CH), 6.59 (d,
J ¼ 8.0 Hz, 1H, ArH), 6.92 (td, J1 ¼ 7.4 Hz, J2 ¼ 0.7 Hz,
1H, ArH), 7.30 (td, J1 ¼ 7.3 Hz, J2 ¼ 1.5 Hz,1H, ArH), 7.58
(d, J ¼ 8.7 Hz, 2H, ArH), 8.00 (dd, J1 ¼ 3.9 Hz, J2 ¼ 1.2 Hz,
1H, ArH), 8.22 (d, J ¼ 8.7 Hz, 2H, ArH) ppm.
Table 4
Dependence of water on the activity of [Hmim][NO3] in the reaction
of isatoic anhydride, 4-chlorobenzaldehyde, and ethylamine.a
3-Ethyl-2-(3-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4e). (95%), mp 176–178ꢁC; IR (KBr) tmax ¼ 3275, 2972,
1625, 1580, 1525, 1475, 1424, 1350, 1300, 1281, 1219, 1103,
Entry
Water content % (w/w)
Yield (%)b
1
2
3
4
0
15
30
60
94
94
86
73
925, 758, 700 cmꢀ1 1H-NMR (500 MHz, CDCl3): dH 1.07
;
(t, J ¼ 7.1 Hz, 3H, CH3), 2.78–2.85 (m, 1H, NCH2CH3),
3.92–3.99 (m, 1H, NCH2CH3), 5.74 (d, J ¼ 2.7 Hz, 1H, NH),
6.33 (d, J ¼ 1.8 Hz, 1H, CH), 6.47 (d, J ¼ 8.0 Hz, 1H, ArH),
6.64 (td, J1 ¼ 7.5 Hz, J2 ¼ 0.7 Hz, 1H, ArH), 7.08 (td, J1 ¼
7.7 Hz, J2 ¼ 1.5 Hz, 1H, ArH), 7.37 (t, J ¼ 8.0 Hz, 1H,
ArH), 7.57 (d, J ¼ 7.7 Hz, 1H, ArH), 7.74 (d, J ¼ 7.8 Hz,
a Reaction conditions: isatoic anhydride (1.1 mmol), ethylamine
(1 mmol), 4-chlorobenzaldehyde (1 mmol), IL (1 mmol).
b Isolated yield.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2011
One-Pot Synthesis of 2,3-Disubstituted-2,3-dihydroquinazolin-4(1H)-ones
Using [Hmim][NO3]: An Eco-Friendly Protocol
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(500 MHz, CDCl3): d 1.19 (t, J ¼ 7.2 Hz, 3H, CH3), 2.91–
2.98 (m, 1H, NCH2CH3), 3.99–4.06 (m, 1H, NCH2CH3), 4.76
(br, s, 1H, NH), 5.82 (s, 1H, CH), 6.58 (d, J ¼ 8.1 Hz, 1H,
ArH), 6.90 (td, J1 ¼ 7.8 Hz, J2 ¼ 0.9 Hz, 1H, ArH), 7.27–
7.30 (m, 1H, ArH), 7.51 (d, J ¼ 8.3 Hz, 2H, ArH), 7.65 (d,
J ¼ 8.4 Hz, 2H, ArH), 7.97 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.3 Hz,
1H, ArH) ppm; 13C-NMR (125 MHz, CDCl3): d 13.4, 40.4,
71.5, 113.5, 115.1, 116.8, 118.6, 120.3, 127.5, 128.9, 133.2,
134.1, 144.6, 154.7, 163.0 ppm; MS (EI, 70 eV): m/z ¼ 277
(Mþ, 2), 175 (50), 147 (62), 102 (100).
(t, J ¼ 7.2 Hz, 3H, CH3), 3.04–3.11 (m, 1H, NCH2CH3) 4.00–
4.07 (m, 1H, NCH2CH3), 4.79 (br, s, 1H, NH), 6.64 (d, J ¼
8.0 Hz, 1H, CH), 6.89–6.94 (m, 2H, ArH), 7.06 (dd, J1 ¼ 3.4
Hz, J2 ¼ 0.7 Hz, 1H, ArH), 7.22 (dd, J1 ¼ 5.0 Hz, J2 ¼ 1.1
Hz, 1H, ArH), 7.29–7.32 (m, 1H, ArH), 7.98 (dd, J1 ¼ 7.8 Hz,
J2 ¼ 1.5 Hz, 1H, ArH) ppm; 13C-NMR (125 MHz, CDCl3): d
13.6, 40.1, 68.1, 115.2, 117.1, 120.2, 126.4, 126.8, 128.9,
133.8, 144.2, 145.2, 162.7 ppm; MS (EI, 70 eV): m/z ¼ 260
(M þ 2, 21), 259 (M þ 1, 56), 258 (Mþ, 87), 257 (M ꢀ 1,
77), 229 (77), 175 (99), 147 (95), 92 (100); Anal. Calcd. for
C14H14N2OS: C, 65.09; H, 5.46; N, 10.84; S, 12.41; Found: C,
65.10; H, 5.55; N, 10.84; S, 11.94.
3-Ethyl-2-(3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-
one (4h). (90%), mp 11–116ꢁC; IR (KBr) tmax ¼ 3296, 2965,
1632, 1508, 1414, 1306, 1252, 1178, 1028, 746 cmꢀ1
;
1H-
3-Ethyl-2-styryl-2,3-dihydroquinazolin-4(1H)-one (4l). (95%),
mp 132–134ꢁC; IR (KBr) tmax ¼ 3306, 2936, 1622, 1510,
1475, 1427, 1369, 1290, 1207, 1153, 1090, 1028, 987, 878,
NMR (500 MHz, CDCl3): d 1.18 (t, J ¼ 7.1 Hz, 3H, CH3),
2.95–3.02 (m, 1H, NCH2CH3), 3.81 (s, 3H, OCH3), 3.92–3.99
(m, 1H, NCH2CH3), 4.46 (br, s, 1H, NH), 5.78 (s, 1H, CH),
6.55 (d, J ¼ 8.0 Hz, 1H, ArH), 6.88–7.02 (m, 4H, ArH), 7.28–
7.32 (m, 2H, ArH), 8.00 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.4 Hz, 1H,
ArH) ppm; 13C-NMR (125 MHz, CDCl3): d 13.3, 39.9, 55.7,
72.5, 112.7, 114.6, 115.1, 116.7, 119.4, 119.7, 128.9, 130.5,
133.7, 141.9, 154.5, 160.5, 163.3 ppm; MS (EI, 70 eV): m/z ¼
282 (Mþ, 3), 253 (17), 175 (100), 147 (31), 119 (35), 92 (84).
785, 750 cmꢀ1
;
1H-NMR (500 MHz, CDCl3): d 1.29 (t, J ¼
7.1 Hz, 3H, CH3), 3.13–3.21 (m, 1H, NCH2CH3), 4.01–4.08
(m, 1H, NCH2CH3), 4.44 (br, s, 1H, NH), 5.23 (d, J ¼ 8.2 Hz,
1H, CH), 6.41–6.46 (m, 1H, ArH), 6.61–6.66 (m, 2H, ArH),
6.99 (td, J1 ¼ 7.5 Hz, J2 ¼ 0.7 Hz, 1H, ArH), 7.29–7.41 (m,
6H, ArH), 7.98 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.3 Hz, 1H, ArH) ppm;
13C-NMR (125 MHz, CDCl3): d 13.7, 39.7, 71.8, 114.9, 116.8,
119.8, 126.5, 127.2, 129.0, 129.1, 133.5, 133.7, 135.8, 145.5,
162.7 ppm; MS (EI, 70 eV): m/z ¼ 280 (M þ 2, 8), 279 (M þ
1, 47), 278 (Mþ, 79), 277 (M ꢀ 1, 70), 249 (69), 175 (100),
147 (95), 146 (76); Anal. Calcd. for C18H18N2O: C, 77.67; H,
6.52; N, 10.06; Found: C, 77.15; H, 6.30; N, 9.93.
2-(3,4-Dimethoxyphenyl)-3-ethyl-2,3-dihydroquinazolin-4(1H)-
one (4i). (94%), mp 146–149ꢁC; IR (KBr) tmax ¼ 3346, 2974,
2835, 1651, 1610, 1510, 1450, 1315, 1236, 1134, 1024, 889,
1
856, 806, 762, 696 cmꢀ1; H-NMR (500 MHz, CDCl3): d 1.11
(t, J ¼ 7.1 Hz, 3H, CH3), 2.93–3.00 (m, 1H, NCH2CH3),
3.81–3.90 (m, 1H, NCH2CH3), 3.82 (s, 3H, OCH3), 3.88
(s, 3H, OCH3), 4.68 (br, s, 1H, NH), 5.75 (s, 1H, CH), 6.57
(d, J ¼ 8.0 Hz, 1H, ArH), 6.81–6.85 (m, 2H, ArH), 6.94 (dd,
J1 ¼ 8.1 Hz, J2 ¼ 1.97 Hz, 1H, ArH), 7.00 (d, J ¼ 1.97 Hz,
1H, ArH), 7.25 (td, J1 ¼ 7.7 Hz, J2 ¼ 1.5 Hz, 1H, ArH), 7.94
(dd, J1 ¼ 7.8 Hz, J2 ¼ 1.3 Hz, 1H, ArH) ppm; 13C-NMR (125
MHz, CDCl3): d 13.3, 39.6, 56.3, 56.3, 72.6, 110.0, 111.3,
114.5, 116.6, 119.5, 120.0, 128.8, 132.6, 133.7, 145.9, 149.8,
150.3, 163.6 ppm; MS (EI, 70 eV): m/z ¼ 314 (M þ 2, 8),
313 (M þ 1, 43), 312 (Mþ, 74), 311 (M ꢀ 1, 59), 283 (56),
175 (100), 147 (99); Anal. Calcd. for C18H20N2O3: C, 69.21;
H, 6.45; N, 8.97; Found: C, 69.10; H, 6.45; N, 8.24.
3-Ethyl-2-(2-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4m). (93%), mp 146–149ꢁC; IR (KBr) tmax ¼ 3287, 2990,
2934, 1622, 1421, 1325, 1167, 1045, 1028, 878, 827, 756, 696
cmꢀ1
;
1H-NMR (500 MHz, CDCl3): d 1.26 (t, J ¼ 7.1 Hz,
3H, CH3), 2.85–2.92 (m, 1H, NCH2CH3), 4.12–4.19 (m, 1H,
NCH2CH3), 5.09 (br, s, 1H, NH), 6.15 (s, 1H, CH), 6.52 (d,
J ¼ 8.0 Hz, 1H, ArH), 6.83 (td, J1 ¼ 7.8 Hz, J2 ¼ 0.8 Hz,
1H, ArH), 7.18–7.30 (m, 4H, ArH), 7.42 (dd, J1 ¼ 7.9 Hz, J2
¼ 1.0 Hz, 1H, ArH), 7.97 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.3 Hz, 1H,
ArH) ppm; 13C-NMR (125 MHz, CDCl3): d 13.6, 40.6, 68.2,
114.9, 116.5, 119.7, 127.8, 127.9, 128.8, 130.5, 130.6, 132.3,
133.9, 137.2, 144.9, 163.6 ppm; MS (EI, 70 eV): m/z ¼ 288
(M þ 2, 8), 286 (Mþ, 24), 257 (12), 175 (100), 147 (94);
Anal. Calcd. for C16H15ClN2O: C, 67.02; H, 5.27; N, 9.77;
Found: C, 67.10; H, 5.44; N, 9.67.
3-Ethyl-2-(naphthalen-2-yl)-2,3-dihydroquinazolin-4(1H)-
one (4j). (87%), mp 140–143ꢁC; IR (KBr) tmax ¼ 3300,
2974, 2934, 1624, 1514, 1416, 1323, 1169, 1063, 953, 862,
750, 693 cmꢀ1
;
1H-NMR (500 MHz, CDCl3): d 1.15 (t, J ¼
3-Butyl-2-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4n). (97%), mp 150–151ꢁC; IR (KBr) tmax ¼ 3300, 2938,
7.1 Hz, 3H, CH3), 2.95–3.02 (m, 1H, NCH2CH3), 3.94–4.01
(m, 1H, NCH2CH3), 4.84 (br, s, 1H, NH), 5.95 (s, 1H, CH),
1628, 1515, 1487, 1418, 1323, 1090, 1016, 852, 748 cmꢀ1
;
6.56 (d, J ¼ 8.0 Hz, 1H, ArH), 6.85 (td, J1 ¼ 7.6 Hz, J2
¼
1H-NMR (500 MHz, CDCl3): d 0.92 (t, J ¼ 7.4 Hz, 3H, CH3),
1.32–1.39 (m, 2H, CH2), 1.55–1.63 (m, 2H, CH2), 2.75–2.81
(m, 1H, NCH2CH2), 3.98–4.05 (m, 1H, NCH2CH2), 4.54 (br,
s, 1H, NH), 5.75 (s, 1H, CH), 6.56 (d, J ¼ 7.8 Hz, 1H, ArH),
6.89 (td, J1 ¼ 6.9 Hz, J2 ¼ 0.9 Hz, 1H, ArH), 7.26–7.30 (m,
1H, ArH), 7.32–7.36 (m, 4H, ArH), 7.98 (dd, J1 ¼ 7.8 Hz,
J2 ¼ 1.4 Hz, 1H, ArH).
0.8 Hz, 1H, ArH), 7.25 (td, J1 ¼ 7.8 Hz, J2 ¼ 1.5 Hz, 1H,
ArH), 7.52–7.56 (m, 2H, ArH), 7.59 (dd, J1 ¼ 8.6 Hz, J2
¼
1.8 Hz, 1H, ArH), 7.79 (s, 1H, ArH), 7.84–7.86 (m, 3H, ArH),
8.01 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.4 Hz, 1H, ArH) ppm; 13C-NMR
(125 MHz, CDCl3): d 13.3, 40.0, 72.7, 114.7, 116.5, 119.6,
124.5, 126.4, 127.1, 127.2, 128.2, 128.6, 128.9, 129.6, 133.4,
133.8, 134.1, 137.6, 145.7, 163.5 ppm; MS (EI, 70 eV): m/z ¼
304 (M þ 2, 3), 303 (M þ 1, 14), 302 (Mþ, 54), 301 (M ꢀ 1,
17), 273 (23), 175 (100), 147 (90); Anal. Calcd. for
C20H18N2O: C, 79.44; H, 6.00; N, 9.26; Found: C, 79.62; H,
6.17; N, 9.17.
3-Butyl-2-(2,4-dichlorophenyl)-2,3-dihydroquinazolin-4(1H)-
one (4o). (90%), mp 135–138ꢁC; IR (KBr) tmax ¼ 3265,
3030, 2949, 2868, 1628, 1524, 1470, 1383, 1323, 1240, 1198,
1171, 1153, 1099, 1042, 930, 839, 818, 741, 692, 615, 569,
532, 461 cmꢀ1
;
1H-NMR (500 MHz, CDCl3): d 0.97 (t, J ¼
3-Ethyl-2-(thiophen-2-yl)-2,3-dihydroquinazolin-4(1H)-one
(4k). (91%), mp 126–128ꢁC; IR (KBr) tmax ¼ 3277, 3084,
2976, 2936, 1620, 1508, 1373, 1321, 1252, 1209, 1151, 1057,
7.4 Hz, 3H, CH3), 1.41–1.47 (m, 2H, CH2), 1.63–1.69 (m, 2H,
CH2), 2.66–2.72 (m, 1H, NCH2CH2), 4.16–4.22 (m, 1H,
NCH2CH2), 5.03 (br, s, 1H, NH), 6.05 (s, 1H, CH), 6.53 (d, J
¼ 8.0 Hz, 1H, ArH), 6.86 (td, J1 ¼ 7.6 Hz, J2 ¼ 0.9 Hz, 1H,
1
955, 851, 775, 698 cmꢀ1; H-NMR (500 MHz, CDCl3): d 1.22
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1426
I. Mohammadpoor-Baltork, A. R. Khosropour, M. Moghadam, S. Tangestaninejad,
V. Mirkhani, M. Soltani, and A. Mirjafari
Vol 48
1
ArH), 7.17–7.26 (m, 3H, ArH), 7.45 (d, J ¼ 1.7 Hz, 1H,
ArH), 7.97 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.3 Hz, 1H, ArH) ppm;
13C-NMR (125 MHz, CDCl3): d 14.2, 20.5, 30.5, 45.5, 68.2,
115.0, 116.5, 120.0, 128.0, 128.7, 128.9, 130.5, 133.0, 134.0,
135.7, 144.5, 163.8 ppm; MS (EI, 70 eV): m/z ¼ 350 (M þ 2,
5), 349 (M þ 1, 2), 348 (Mþ, 8), 291 (12), 203 (100), 147
(91); Anal. Calcd. for C18H18Cl2N2O: C, 61.90; H, 5.19; N,
8.02; Found: C, 61.93; H, 5.19; N, 8.19.
704 cmꢀ1; H-NMR (500 MHz, CDCl3): d 0.95 (t, J ¼ 7.5 Hz,
3H, CH3), 1.36–1.43 (m, 2H, CH2), 1.58–1.71 (m, 2H, CH2),
2.91–2.96 (m, 1H, NCH2CH2), 4.06–4.12 (m, 1H, NCH2CH2),
4.66 (br, s, 1H, NH), 6.00 (s, 1H, CH), 6.64 (d, J ¼ 8.0 Hz, 1H,
ArH), 6.91–6.94 (m, 2H, ArH), 7.04 (d, J ¼ 3.4 Hz, 1H, ArH),
7.22 (dd, J1 ¼ 5.0 Hz, J2 ¼ 1.0 Hz, 1H, ArH), 7.26–7.33 (m, 1H,
ArH), 7.99 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.3 Hz, 1H, ArH) ppm; 13C-
NMR (125 MHz, CDCl3): d 14.2, 20.6, 30.4, 45.0, 68.3, 115.3,
117.3, 120.3, 126.3, 126.9, 128.9, 133.8, 144.2, 145.0, 162.9
ppm; MS (EI, 70 eV): m/z ¼ 287 (M þ 1, 5), 286 (Mþ, 18), 285
(M ꢀ 1, 11), 229 (27), 203 (67), 147 (100), 146 (12); Anal.
Calcd. for C16H18N2OS: C, 67.10; H, 6.33; N, 9.78, S, 11.20;
Found: C, 66.52; H, 6.26; N, 9.42, S, 10.76.
3-Butyl-2-(4-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4p). (94%), mp 137–139ꢁC; IR (KBr) tmax ¼ 3300, 3078,
2938, 2872, 1632, 1525, 1485, 1408, 1350, 1319, 1234, 1153,
;
1070, 1016, 930, 874, 825, 743 cmꢀ1 1H-NMR (500 MHz,
CDCl3): d 0.91 (t, J ¼ 7.4 Hz, 3H, CH3), 1.34–1.40 (m, 2H,
CH2), 1.56–1.64 (m, 2H, CH2), 2.76–2.82 (m, 1H, NCH2CH2),
4.08–4.13 (m, 1H, NCH2CH2), 5.16 (br, s, 1H, NH), 5.85 (s, 1H,
CH), 6.61 (d, J ¼ 8.0 Hz, 1H, ArH), 6.87 (td, J1 ¼7.3 Hz, J2 ¼
0.9 Hz, 1H, ArH), 7.27 (td, J1 ¼ 7.2 Hz, J2 ¼ 1.4 Hz, 1H, ArH),
7.54 (d, J ¼ 8.7 Hz, 2H, ArH), 7.94 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.2
Hz, 1H, ArH), 8.17 (dd, J1 ¼ 6.9 Hz, J2 ¼ 1.8 Hz, 2H, ArH)
ppm; 13C-NMR (125 MHz, CDCl3): d 14.2, 20.5, 30.4, 45.5,
71.2, 115.3, 116.8, 120.2, 124.6, 127.6, 128.8, 134.2, 144.6,
147.6, 148.6, 163.3 ppm; MS (EI, 70 eV): m/z ¼ 325 (Mþ, 2),
203 (87), 147 (100), 119 (37); Anal. Calcd. for C18H19N3O3: C,
66.45; H, 5.89; N, 12.91; Found: C, 66.37; H, 5.95; N, 12.70.
3-Benzyl-2-(naphthalen-2-yl)-2,3-dihydroquinazolin-4(1H)-
one (4t). (85%), mp 157–159ꢁC; IR (KBr) tmax ¼ 3296, 3028,
2927, 1629, 1487, 1425, 1354, 1313, 752, 692 cmꢀ1; H-NMR
1
(500 MHz, CDCl3) d 3.75 (d, J ¼ 15.3, 1H, CH), 4.64 (br, s,
1H, NH), 5.70 (d, J ¼ 15.3, 1H, CH), 5.83 (s, 1H, CH), 6.50
(d, J ¼ 7.8, 1H, ArH), 6.90 (td, J1 ¼ 7.5 Hz, J2 ¼ 0.94, 1H,
ArH), 7.26–7.33 (m, 6H, ArH), 7.5 (dd, J1 ¼ 7.8 Hz, J2
¼
1.8, 1H, ArH), 7.53–7.55 (m, 2H, ArH), 7.7 (d, J ¼ 1.2, 1H,
ArH), 7.81–7.87 (m, 3H, ArH), 8.1 (dd, J1 ¼ 7.8 Hz, J2
¼
1.5, 2H, ArH) ppm; 13C-NMR (500 MHz, CDCl3) d 47.4,
71.6, 114.8, 116, 119.7, 124.3, 126.4, 127.1, 127.2, 128.1,
128.5, 128.6, 129, 129.3, 129.7, 133.3, 134, 134.1, 137, 137.2,
145.5, 163.7 ppm; MS (EI) m/z ¼ 364.16 (Mþ), 273.12 (2.76),
237.17 (4.54), 91.13 (100), 65.14 (25.58).
3-Butyl-2-(3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-
one (4q). (90%), mp 102–105ꢁC; IR (KBr) tmax ¼ 3304, 2957,
2833, 1630, 1508, 1500, 1412, 1323, 1250, 1148, 941, 856, 791,
1
760 cmꢀ1; H-NMR (500 MHz, CDCl3): d 0.91 (t, J ¼ 7.3 Hz,
3-Benzyl-2-(3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-
one (4u). (91%), mp 169–171ꢁC; IR (KBr) tmax ¼ 3268,
2929, 2835, 1622, 1483,1402, 1352, 1253, 1174, 1029, 829,
;
758, 723, 694 cmꢀ1 1H-NMR (500 MHz, CDCl3) d 3.73 (d,
3H, CH3), 1.31–1.38 (m, 2H, CH2), 1.55–1.63 (m, 2H, CH2),
2.78–2.84 (m, 1H, NCH2CH2), 3.79 (s, 3H, OCH3), 3.97–4.03
(m, 1H, NCH2CH2), 4.54 (br, s, 1H, NH), 5.74 (s, 1H, CH), 6.55
(d, J ¼ 7.8 Hz, 1H, ArH), 6.87 (td, J1 ¼ 7.5 Hz, J2 ¼ 0.9 Hz,
1H, ArH), 6.89–6.92 (m, 1H, ArH), 6.94 (t, J ¼ 2.3 Hz, 1H,
ArH), 6.97 (d, J ¼ 7.7 Hz, 1H, ArH), 7.24–7.30 (m, 2H, ArH),
7.99 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.5 Hz, 1H, ArH) ppm; 13C-NMR
(125 MHz, CDCl3): d 14.2, 20.6, 30.2, 44.9, 55.7, 72.5, 112.6,
114.6, 115.0, 116.8, 119.2, 119.7, 128.9, 130.4, 133.7, 142.0,
145.4, 160.5, 163.4 ppm; MS (EI, 70 eV): m/z ¼ 312 (M þ 2,
3), 311 (M þ 1, 12), 310 (Mþ, 52), 309 (M ꢀ 1, 12), 253 (42),
203 (100), 147 (99); Anal. Calcd. for C19H22N2O2: C, 73.52; H,
7.14; N, 9.03; Found: C, 72.98; H, 7.01; N, 8.93.
J ¼ 15.3, 1H, CH), 3.82 (s, 3H, CH3) 4.55 (br, s, 1H, NH),
5.57 (d, J ¼ 15.3, 1H, CH), 5.63 (s, 1H, CH), 6.55 (d, J ¼
7.95, 1H, ArH), 6.8–6.9 (m, 3H, ArH), 7.23 (d, J ¼ 2.8, 4H,
ArH) 7.27–7.34 (m, 4H, ArH), 8.00 (dd, J1 ¼ 7.8 Hz, J2
¼
1.5, 1H, ArH); 13C-NMR (500 MHz, CDCl3) d 47.2, 55.8,
71.3, 114.6, 114.7, 116.1, 119.6, 127.8, 128.4, 128.5, 128.9,
129.2, 131.8, 134, 137.3, 145.7, 160.7, 163.7 ppm; MS (EI) m/
z ¼ 344.41 (Mþ), 253.18 (20.73), 237.17 (20.43), 91.00 (100),
65.00 (26.83).
3-Benzyl-2-(4-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one
(4v). (87%), mp 190–193ꢁC; IR (KBr) tmax ¼ 3294, 2941,
3-Butyl-2-(naphthalen-2-yl)-2,3-dihydroquinazolin-4(1H)-
one (4r). (87%), mp 144–146ꢁC; IR (KBr) tmax ¼ 3300,
2953, 2870, 1624, 1510, 1440, 1383, 1304, 1232, 1171, 1076,
;
904, 827, 752, 696, 550, 780 cmꢀ1 1H-NMR (500 MHz,
2810, 1631,1487, 1413, 1348, 763, 698 cmꢀ1 1H-NMR (500
;
MHz, CDCl3) d 3.78 (d, J ¼ 15.3, 1H, CH), 4.55 (br, s, 1H,
NH), 5.68 (d, J ¼ 15.3, 1H, CH), 5.71 (s, 1H, CH), 6.59 (d,
J ¼ 7.95, 1H, ArH), 6.95 (td, J1 ¼ 15.1 Hz, J2 ¼ 0.6, 1H,
ArH), 7.27 (dd, J1 ¼ 7 Hz, J2 ¼ 1.6, 2H, ArH), 7.29–7.36 (m,
4H, ArH), 8 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.4, 1H, ArH), 8.18–8.19
(m, 2H, ArH) ppm; 13C-NMR (500 MHz, CDCl3) d 47.8, 70.3,
115.2, 120.5, 124.6, 127.7, 128.2, 128.4, 129.2, 129.4, 134.4,
136.5, 144.5, 146.8, 163.3 ppm; MS (EI) m/z ¼ 359.13 (Mþ),
268.13 (2.52), 237.16 (6.28), 91.04 (100), 65.03 (29.44).
CDCl3): d 0.90 (t, J ¼ 7.4 Hz, 3H, CH3), 1.32–1.37 (m, 2H,
CH2), 1.59–1.65 (m, 2H, CH2), 2.81–2.87 (m, 1H, NCH2CH2),
4.05–4.11 (m, 1H, NCH2CH2), 4.60 (br, s, 1H, NH), 5.95 (s,
1H, CH), 6.54 (d, J ¼ 8.0 Hz, 1H, ArH), 6.88 (t, J ¼ 7.4 Hz,
1H, ArH), 7.26 (td, J1 ¼ 7.6 Hz, J2 ¼ 1.4 Hz, 1H, ArH),
7.53–7.57 (m, 3H, ArH), 7.78 (s, 1H, ArH), 7.85–7.87 (m, 3H,
ArH), 8.03 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.3 Hz, 1H, ArH); 13C-
NMR (125 MHz, CDCl3): d 14.2, 20.6, 30.2, 45.0, 72.7,
114.7, 119.8, 124.3, 126.2, 127.1, 128.2, 128.6, 128.9, 129.7,
133.4, 133.8, 134.0, 137.5, 145.3, 163.5; MS (EI, 70 eV): m/z
¼ 330 (Mþ, 3), 203 (20), 147 (23), 127 (100), 119 (48); Anal.
Calcd. for C22H22N2O: C, 79.97; H, 6.71; N, 8.48; Found: C,
79.49; H, 6.68; N, 8.43.
3-Benzyl-2-(thiophen-2-yl)-2,3-dihydroquinazolin-4(1H)-one
(4w). (88%), mp 175–177ꢁC; IR (KBr) tmax ¼ 3288, 2943,
2810, 1625, 1516, 1411, 1305, 786, 698 cmꢀ1; H-NMR (500
1
MHz, CDCl3) d 3.78 (d, J ¼ 15.4, 1H, CH), 5.44 (br, s, 1H,
NH), 5.55 (d, J ¼ 15.4, 1H, CH), 5.80 (s, 1H, CH), 6.60 (d,
J ¼ 8.0, 1H, ArH), 6.81–6.85 (m, 2H, ArH), 6.89 (d, J ¼ 2.7,
1H, ArH), 7.13 (dd, J1 ¼ 5.0 Hz, J2 ¼ 1.0, 1H, ArH), 7.20–
7.36 (m, 3H, ArH), 7.94 (dd, J1 ¼ 7.8 Hz, J2 ¼ 1.4, 1H, ArH)
ppm; 13C-NMR (500 MHz, CDCl3) d 47.2, 66.9, 115.3, 116.2,
3-Butyl-2-(thiophen-2-yl)-2,3-dihydroquinazolin-4(1H)-one
(4s). (90%), 99–101ꢁC; IR (KBr) tmax ¼ 3292, 2949, 2868,
1632, 1502, 1412, 1315, 1242, 1153, 1113, 1030, 912, 860, 762,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2011
One-Pot Synthesis of 2,3-Disubstituted-2,3-dihydroquinazolin-4(1H)-ones
Using [Hmim][NO3]: An Eco-Friendly Protocol
1427
Bernard, H. Pharmazie 1992, 47, 91; (e) Baker, B. R.; Schaub, R. E.;
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119.6, 126.2, 126.5, 126.7, 127.9, 128.4, 128.9, 129.0, 134.0,
137.2, 143.7, 145.6, 163.1 ppm; MS (EI) m/z ¼ 320.18 (2.84)
(Mþ), 69.16 (52.48), 61.07 (59.57), 57.19 (100).
Acknowledgments. The authors thank the ‘‘Center of Excellence
of Chemistry of the University of Isfahan’’ and the Research Coun-
cil of the University of Isfahan for financial support of this work.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet