Synthesis of 2-arylquinazolin-4(3H)-one derivatives catalyzed by iodine in [bmim+][BF-4]

Article abstract of DOI:10.1080/00397910903318609

Controlling selectivity of the reactions of aromatic aldehydes and 2-aminobenzamide in ionic liquid catalyzed by iodine at either room temperature or at 80°C under nitrogen resulted in the synthesis of (E)-Schiff bases, 2,3-dihydro-2-arylquinazolin-4(1H)-one and 2-arylquinazolin-4(3H)-one derivatives, in excellent yields. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903318609

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Synthesis of 2-Arylquinazolin-4(3H)-
one Derivatives Catalyzed by Iodine in
[bmim+][ ]
Xiang-Shan Wang a b , Ke Yang a , Mei-Mei Zhang b & Chang-Sheng Yao
a
a School of Chemistry and Chemical Engineering, Xuzhou Normal
University, Xuzhou, Jiangsu, China
b Key Laboratory of Biotechnology on Medical Plants, Xuzhou,
Jiangsu, China
Version of record first published: 05 Aug 2010.
To cite this article: Xiang-Shan Wang , Ke Yang , Mei-Mei Zhang & Chang-Sheng Yao (2010):
Synthesis of 2-Arylquinazolin-4(3H)-one Derivatives Catalyzed by Iodine in [bmim+][ ], Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
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Synthetic Communications1, 40: 2633–2646, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903318609
SYNTHESIS OF 2-ARYLQUINAZOLIN-4(3H)-ONEþ
DERIVATIVES CATALYZED BY IODINE IN [bmim ][BFꢀ4 ]
Xiang-Shan Wang,1,2 Ke Yang,1 Mei-Mei Zhang,2 and
Chang-Sheng Yao1
1School of Chemistry and Chemical Engineering, Xuzhou Normal University,
Xuzhou, Jiangsu, China
2Key Laboratory of Biotechnology on Medical Plants, Xuzhou,
Jiangsu, China
Controlling selectivity of the reactions of aromatic aldehydes and 2-aminobenzamide in
ionic liquid catalyzed by iodine at either room temperature or at 80 ꢁC under nitrogen
resulted in the synthesis of (E)-Schiff bases, 2,3-dihydro-2-arylquinazolin-4(1H)-one
and 2-arylquinazolin-4(3H)-one derivatives, in excellent yields.
Keywords: 2-Aminobenzamide; iodine; ionic liquid; quinazolin-4(1H)-one; synthesis
INTRODUCTION
Control of selectivity, for example, chemo- and regioselectivities, is among the
most important objectives in organic chemistry. Many different process parameters
such as temperature, pressure, solvent, catalyst type, and other factors can be utilized
to modulate the selectivity of synthetic transformations.[1] Quinazoline and its
derivatives have recently been evaluated as antagonists of various biological
receptors, such as treating 5-HT5A receptor–related diseases,[2] antagonists of calci-
tonin gene–related peptide receptors,[3] and vasopressin V3 receptor antagonists.[4]
2-Substituted quinazolines have also been tested for their potential activities (e.g.,
anti-inflammatory,[5] antihypertensive,[6] anticancer,[7] antitumor,[8] and antibacter-
ial[9] activities. Hence, the synthesis of quinazoline derivatives is currently of great
interest. Various methods[10] reported for the synthesis of 2-arylquinazoline were
based on 2-aminobenzamide with aromatic aldehyde or on the condensation of isa-
toic anhydride and amines with aldehydes. However, these reported methods are not
straightforward and involve various disadvantages such as poor yields, prolonged
reaction times, and the use of toxic organic reagents.
Room-temperature ionic liquids (RTILs), especially those based on the 1-N-
alkyl-3-methyl imidazolium cation, have shown great promise as attractive
alternatives to conventional solvents.[11] These materials are also widely used in
Received April 29, 2009.
Address correspondence to Xiang-Shan Wang, School of Chemistry and Chemical Engineering,
Xuzhou Normal University, Xuzhou, Jiangsu 221116, China. E-mail: xswang1974@yahoo.com
2633

2634
X.-S. WANG ET AL.
homogeneous catalysis,[12] electrochemistry,[13] photochemistry,[14] and liquid crys-
tals.[15] The distinctive property of RTILs is that they have essentially no vapor
pressure, which makes them optimal replacements for the volatile organic solvents
traditionally used as industrial solvents. Another feature of ILs is their ability to
be reused many times. Because of this advantage, ILs have made significant contri-
butions to green chemistry and have been used widely as reaction media in organic
chemistry.[16]
As a part of a program for the synthesis of new suitably functionalized hetero-
cyclic compounds of potential biological activity in green media,[17] herein we report
a green synthesis of 2-arylquinazoline derivatives by controlling the reactions of aro-
matic aldehyde and 2-aminobenzamide in an IL catalyzed by iodine at either room
temperature or 80 ꢁC.
RESULTS AND DISCUSSION
When the reþaction of aromatic aldehyde 1 and 2-aminobenzamide 2 was per-
formed in [bmim ][BFꢀ4 ] at 80 ꢁC in the presence of iodine, excellent yields of
2-arylquinazolin-4(3H)-one derivatives 3 were obtained (Scheme 1).
At completion, monitored by thin-layer chromatography (TLC), the reaction
mixture was allowed to return to room temperature. A small amount of water was
added to the mixture, and the solid was isolated by filtration. The water in the filtrate
was removed by distillation under reduced pressure, and the IL in the residue was
then recovered for reuse by evaporating at 80 ꢁC for several hours in a vacuum.
Investigations using benzaldehyde and 2-aminobenzamide as model substrates
showed the successive reuse of the recycled IL. Even in the fourth round, the yield
of the product 3a is fairly high (96%).
To demonstrate the efficiency and the applicability of the present method, we
performed reactions of a variety of aromatic aldehydes 1 with 2 at 80 ꢁC in
[bmimþ][BFꢀ4 ]. As shown in Table 1, we can see that a series of 1 [with the aromatic
ring containing either electron-withdrawing groups (such as halide, nitro) or
electron-donating groups (such as alkyl group)] reacted well with 2 to give the
corresponding products 3 in excellent yields under the same reaction conditions.
We concluded that no obvious effects of electrons and nature of substituents on
the aromatic ring were observed in the tested reactions.
Although the detailed mechanism of this reaction has not been clarified yet, the
formation of 2-arylquinazolin-4(3H)-one derivatives 3 can be explained by a possible
mechanism presented in Scheme 2. The Schiff base 4 may be formed by the reaction
of aromatic aldehyde and 2-aminobenzamide, and then the intramolecular nucleo-
=
philic addition reaction between the amino group and C N double bond takes place
Scheme 1. Iodine catalyzed the reactions of 1 and 2 in ionic liquid at 80 ꢁC.

SYNTHESIS OF 2-ARYLQUINAZOLIN-4(3H)-ONE DERIVATIVES
Table 1. Synthesis of 3 in IL at 80 ꢁC catalyzed by iodinea
2635
Entry
Ar
Products Time (min) Yields (%)b
1
2
C6H5
3a
3b
3c
3d
3e
3f
60
45
30
45
45
30
45
30
30
60
60
60
60
95
93
98
95
95
98
99
96
98
90
90
92
92
2-Thioenyl
4-FC6H4
3-ClC6H4
3
4
5
4-ClC6H4
3,4-Cl2C6H3
4-BrC6H4
6
7
3g
3h
3i
8
3-NO2C6H4
4-NO2C6H4
4-CH3C6H4
4-CH3OC6H4
3,5-(CH3O)2C6H3
2-CH3OC6H4
9
10
11
12
13
3j
3k
3l
3m
aReaction condition: 2 mL [bmimþ][BFꢀ4 ], 2 mmol 1, and
2 mmol 2 at 80 ꢁC.
bIsolated yields.
to give the 2,3-dihydro-2-arylquinazolin-4(1H)-ones 5. Compound 5 aromatizes by
air to give the final 2-arylquinazolin-4(3H)-one derivatives 3.
To gain more insight into the reaction and determine whether the nucleophilic
addition reaction takes place if the reaction is controlled at a slightly lower tempera-
ture, the reaction was carried out at 50 ꢁC, room temperature, and 0 ꢁC, respectively.
To our delight, it was found that the desired Schiff base of (E)-configuration 4 was
selectively obtained successfully in excellent yields at room temperature (Scheme 3),
Scheme 2. Possible mechanism for the formation of products 3.
Scheme 3. Iodine catalyzed the reactions of 1 and 2 in IL at room temperature.

2636
X.-S. WANG ET AL.
Figure 1. Crystal structure of 4e with (E)-configuration and dashed line indicating the intramolecular
NꢀH . . . N hydrogen bond.
with structure of 4d being confirmed by x-ray diffraction analysis (Fig. 1). The results
are summarized in Table 2.
To obtain another intermediate 5, we think the air play a key role in the final
the aromatization. So the same reaction was controlled at 80 ꢁC under dry nitrogen,
with 2,3-dihydro-2-arylquinazolin-4(1H)-ones 5 being obtained in high yields
(Scheme 4). The results are summarized in Table 3. It should be noted that only
2-substituted benzaldehydes gave a satisfied results in this iodine-catalyzed reaction.
The other benzaldehydes we tested all gave aromatized products 5, perhaps the sub-
sequent aromatization preceded unexpectedly in the separation and purification. In
order to find the reason and confirm the structure of 5, the X-ray diffraction analysis
of 5b was carried out. The structure is 2,3-dihydro-2-(2-chlorophenyl)quinazolin-4(1-
H)-one, and the X-ray diffraction analysis reveals that there is a weak non-classical
intra-molecular hydrogen bond CꢀH . . . Cl in the crystal structure (Figure 2).
Perhaps this is the best reason to explain why the subsequent aromatization does
not take place in the 2-substituted benzaldehydes.
Table 2. Synthesis of 4 in IL at room temperature catalyzed by iodinea
Entry
Ar
Products
Time (h)
Yields (%)b
1
2
3
4
5
6
7
8
9
2-ClC6H4
4-ClC6H4
3-ClC6H4
4a
4b
4c
4d
4e
4f
1.5
2
87
90
85
89
85
90
92
88
82
2
3-NO2C6H4
4-NO2C6H4
4-FC6H4
1
1.5
1
4-BrC6H4
2,3-Cl2C6H3
2,4-Cl2C6H3
4g
4h
4i
1.2
2
1
aReaction condition: 2 mL [bmimþ][BF4ꢀ], 2 mmol 1, and 2 mmol 2 at room temperature.
bIsolated yields.

SYNTHESIS OF 2-ARYLQUINAZOLIN-4(3H)-ONE DERIVATIVES
2637
Scheme 4. Iodine catalyzed the reactions of 1 and 2 in ionic liquid at 80 ꢁC under dry nitrogen.
Table 3. Synthesis of 5 catalyzed by iodine in ionic liquid at 80 ꢁC under dry
nitrogena
Entry
Ar
2-FC6H4
2-ClC6H4
Products
Time (min)
Yields (%)b
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
45
45
30
45
30
45
60
60
92
98
98
93
95
90
92
93
2,3-Cl2C6H3
2,4-Cl2C6H3
2-NO2C6H4
2-BrC6H4
2-MeOC6H4
2,3-(MeO)2C6H3
5g
5h
aReaction condition: 2 mL [bmimþ][BFꢀ4 ], 2 mmol 1, and 2 mmol 2 at 80 ꢁC
under dry nitrogen.
bIsolated yields.
Figure 2. Crystal structure of 5b with dashed line indicating the intramolecular CꢀH . . . Cl hydrogen
bond.

2638
X.-S. WANG ET AL.
CONCLUSION
In conclusion, we found
a green method for the syntheses of 2-
arylquinazolin-4(3H)-one derivatives by the reactions of aromatic aldehyde and
2-aminobenzamide in IL catalyzed by iodine. Under dry nitrogen at 80 ꢁC, the same
reaction give unaromatized products of 2,3-dihydro-2-arylquinazolin-4(1H)-ones
using 2-substituted benzaldehydes as reactants. Meanwhile, by controlling the reac-
tion at room temperature, (E)-2-(benzylideneamino)benzamides were obtained in
excellent yields in an iodine-catalyzed IL. The features of this procedure are mild
reaction conditions, excellent yields, operational simplicity, and environmentally
friendly procedure. Meanwhile, [bmimþ][BF4ꢀ] could be reused for several rounds
without significant loss of activity.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
Infrared (IR) spectra were recorded on a Tensor 27 spectrometer in KBr. 1H
NMR spectra were obtained from solution in dimethylsulfoxide (DMSO-d6) with
Me4Si as internal standard using a Bruker-400 spectrometer. High-resolution mass
spectrographic (HRMS) analyses were carried out using a Bruker Micro-TOF-Q-
MS analyzer.
General Procedure for the Synthesis of
2-Arylquinazolin-4(3H)-one
A dry 50-mL flask was charged with aromatic aldehyde (2.0 mmol), 2-amino-
benzamide, and [bmimþ][BF4ꢀ] (2 mL). The reaction mixture was stirred at 80 ꢁC
for 30–60 min and then cooled to room temperature. A small amount of water
(5 mL) was added to the mixture, and the generated yellow solid was filtered off.
The water in the filtrate was removed by distillation under reduced pressure, and
the IL in the residue was then recovered for reuse by evaporating it at 80 ꢁC for
4 h in a vacuum. The crude yellow products were washed with water, purified by
recrystallization from EtOH, and dried at 80 ꢁC for 4 h in a vacuum to give 3.
Selected Data
2-Phenylquinazolin-4(3H)-one 3a. Mp 240–241 ꢁC (lit.[10j] 237 ꢁC). 1H
NMR (DMSO-d6, 400 MHz): dH 7.53–7.40 (m, 4H, ArH), 7.75 (d, J ¼ 7.6 Hz, 1H,
ArH), 7.83–7.85 (m, 1H, ArH), 8.19–8.20 (m, 3H, ArH), 12.55 (s, 1H, NH). IR
(KBr): 3137, 6063, 1669, 1603, 1561, 1571, 1482, 1453, 1344, 1296, 1145, 1104,
943, 825, 769, 695 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H11N2O (M þ Hþ)
223.0871; found 233.0886.
2-(Thienyl)quinazolin-4(3H)-one 3b. Mp 254–255 ꢁC. 1H NMR (DMSO-d6,
400 MHz): dH 7.23–7.25 (m, 1H, ArH), 7.47–7.51 (m, 1H, ArH), 7.66 (d, J ¼ 8.0 Hz,
1H, ArH), 7.79–7.83 (m, 1H, ArH), 7.88 (dd, J ¼ 4.8 Hz, J0 ¼ 0.8 Hz, 1H, ArH), 8.13
(dd, J ¼ 8.0 Hz, J0 ¼ 1.2 Hz, 1H, ArH), 8.24 (dd, J ¼ 7.6 Hz, J0 ¼ 0.8 Hz, 1H, ArH),
12.65 (s, 1H, NH). IR (KBr): 3173, 3054, 1672, 1595, 1564, 1529, 1493, 1471,

SYNTHESIS OF 2-ARYLQUINAZOLIN-4(3H)-ONE DERIVATIVES
2639
1448, 1424, 1345, 1309, 1149, 915, 854, 771, 715 cmꢀ1. HRMS (ESI, m=z): calcd. for
C14H9N2OS (M þ Hþ) 229.0436; found 229.0434.
2-(4-Fluorophenyl)quinazolin-4(3H)-one 3c. Mp 288–289 ꢁC. 1H NMR
(DMSO-d6, 400 MHz): dH 7.37–7.42 (m, 2H, ArH), 7.51–7.55 (m, 1H, ArH), 7.74
(d, J ¼ 8.0 Hz, 1H, ArH), 7.83–7.87 (m, 1H, ArH), 8.15 (dd, J ¼ 8.0 Hz, J0 ¼ 1.2 Hz,
Hz, 1H, ArH), 8.22–8.26 (m, 2H, ArH), 12.59 (s, 1H, NH). IR (KBr): 3172, 3089,
3049, 1678, 1610, 1582, 1519, 1485, 1446, 1346, 1309, 1289, 1236, 1167, 1150, 941,
841, 766 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H9FN2NaO (M þ Naþ) 263.0597;
found 263.0588.
2-(3-Chlorophenyl)quinazolin-4(3H)-one 3d. Mp > 300 ꢁC (lit.[10j] > 300 ꢁC).
1H NMR (DMSO-d6, 400 MHz): dH 7.54–7.61 (m, 2H, ArH), 7.67 (d, J ¼ 7.6 Hz, 1H,
ArH), 7.77 (d, J ¼ 8.0 Hz, 1H, ArH), 7.84–7.88 (m, 1H, ArH), 8.14–8.18 (m, 2H,
ArH), 8.24 (s, 1H, ArH), 12.64 (s, 1H, NH). IR (KBr): 3172, 3063, 3026, 1684,
1610, 1566, 1504, 1474, 1474, 1450, 1346, 1310, 1272, 1154, 1093, 956, 876, 769,
761 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H10ClN2O (M þ Hþ) 257.0482; found
257.0479.
2-(4-Chlorophenyl)quinazolin-4(1H)-one 3e. Mp > 300 ꢁC (lit.[10j] > 300 ꢁC).
1H NMR (DMSO-d6, 400 MHz): dH 7.53–7.57 (m, 1H, ArH), 7.63 (d, J ¼ 8.8 Hz, 2H,
ArH), 7.75 (d, J ¼ 8.4 Hz, 1H, ArH), 7.84–7.88 (m, 1H, ArH), 8.15–8.20 (m, 3H,
ArH), 12.63 (s, 1H, NH). IR (KBr): 3134, 3088, 1679, 1604, 1560, 1480, 1444,
1346, 1312, 1281, 1150, 1121, 1096, 940, 841, 764, 728, 684 cmꢀ1. HRMS (ESI,
m=z): calcd. for C14H10ClN2O (M þ Hþ) 257.0482; found 257.0485.
2-(3,4-Dichlorophenyl)quinazolin-4(3H)-one 3f. Mp > 300 ꢁC. 1H NMR
(DMSO-d6, 400 MHz): dH 7.55–7.58 (m, 1H, ArH), 7.78 (d, J ¼ 8.0 Hz, 2H, ArH),
7.84–7.89 (m, 2H, ArH), 8.45 (d, J ¼ 2.0 Hz, 1H, ArH), 12.65 (s, 1H, NH). IR
(KBr): 3131, 3078, 1678, 1601, 1548, 1480, 1505, 1471, 1444, 1380, 1342, 1303,
1248, 1142, 1029, 956, 888, 833, 767, 722 cmꢀ1. HRMS (ESI, m=z): calcd. for
C14H9Cl2N2O (M þ Hþ) 291.0092; found 291.0105.
2-(4-Bromophenyl)quinazolin-4(3H)-one 3g. Mp 298–300 ꢁC (lit.[10j]
1
296–297 ꢁC). H NMR (DMSO-d6, 400 MHz): dH 7.53–7.57 (m, 1H, ArH), 7.77
(d, J ¼ 8.4 Hz, 3H, ArH), 7.84–7.88 (m, 1H, ArH), 8.12 (d, J ¼ 8.8 Hz, 2H, ArH),
8.16 (dd, J ¼ 8.0 Hz, J0 ¼ 1.2 Hz, 1H, ArH), 12.63 (s, 1H, NH). IR (KBr):
3143, 3029, 1678, 1560, 1508, 1482, 1447, 1394, 1346, 1309, 1275, 1183, 1150,
1066, 1010, 942, 859, 834, 773 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H10BrN2O
(M þ Hþ) 300.9977; found 300.9983.
2-(3-Nitrophenyl)quinazolin-4(3H)-one 3h. Mp > 300 ꢁC (lit.[10j] > 300 ꢁC).
1H NMR (DMSO-d6, 400 MHz): dH 7.53–7.61 (m, 1H, ArH), 7.81–7.89 (m, 3H,
ArH), 8.19 (dd, J ¼ 8.0 Hz, J0 ¼ 1.2 Hz, 1H, ArH), 8.43–8.46 (m, 1H, ArH),
8.61–8.64 (m, 1H, ArH), 9.03–9.04 (m, 1H, ArH), 12.89 (s, 1H, NH). IR (KBr):
3172, 3077, 3032, 1680, 1607, 1571, 1531, 1473, 1452, 1353, 1322, 1153, 963, 870,
845, 770, 704 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H10N3O3 (M þ Hþ)
268.0722; found 268.0715.

2640
X.-S. WANG ET AL.
2-(4-Nitrophenyl)quinazolin-4(3H)-one 3i. Mp > 300 ꢁC (lit.[10j] > 300 ꢁC).
1H NMR (DMSO-d6, 400 MHz): dH 7.57–7.61 (m, 1H, ArH), 7.81 (d, J ¼ 8.0 Hz,
1H, ArH), 7.87–7.91 (m, 1H, ArH), 8.19 (d, J ¼ 8.0 Hz, 1H, ArH), 8.37–8.43 (m,
4H, ArH), 12.86 (s, 1H, NH). IR (KBr): 3170, 3082, 3027, 1608, 1607, 1590, 1523,
1487, 1469, 1452, 1349, 1306, 1151, 1109, 946, 860, 772, 708 cmꢀ1. HRMS (ESI,
m=z): calcd. for C14H10N3O3 (M þ Hþ) 268.0722; found 268.0744.
2-(4-Methylphenyl)quinazolin-4(3H)-one 3j. Mp 239–240 ꢁC (lit.[10j]
240–241 ꢁC). 1H NMR (DMSO-d6, 400 MHz): dH 2.39 (s, 3H, CH3), 7.36 (d,
J ¼ 8.0 Hz, 2H, ArH), 7.49–7.53 (m, 1H, ArH), 7.73 (d, J ¼ 8.0 Hz, 1H, ArH),
7.81–7.85 (m, 1H, ArH), 8.10 (d, J ¼ 8.0 Hz, 2H, ArH), 8.15 (dd, J ¼ 8.0 Hz,
J0 ¼ 1.2 Hz, 1H, ArH), 12.48 (s, 1H, NH). IR (KBr): 3176, 3064, 2960, 1661, 1603,
1486, 1468, 1469, 1446, 1345, 1302, 1287, 1151, 1019, 941, 825, 771 cmꢀ1. HRMS
(ESI, m=z): calcd. for C15H13N2O (M þ Hþ) 237.1028; found 237.1028.
1
2-(4-Methoxyphenyl)quinazolin-4(3H)-one 3k. Mp 255–257 ꢁC. H NMR
(DMSO-d6, 400 MHz): dH 3.85 (s, 3H, CH3O), 7.10 (d, J ¼ 8.8 Hz, 2H, ArH),
7.47–7.51 (m, 1H, ArH), 7.71 (d, J ¼ 8.0 Hz, 1H, ArH), 7.80–7.84 (m, 1H, ArH),
8.14 (d, J ¼ 7.6 Hz, 1H, ArH), 8.19 (d, J ¼ 8.8 Hz, 2H, ArH), 12.42 (s, 1H, NH).
IR (KBr): 3179, 3064, 2994, 2972, 1681, 1603, 1563, 1527, 1484, 1445, 1347, 1321,
1306, 1267, 1250, 1178, 1119, 1032, 942, 836, 766 cmꢀ1. HRMS (ESI, m=z): calcd.
for C15H13N2O2 (M þ Hþ) 253.0977; found 253.0983.
2-(3,5-Dimethoxyphenyl)quinazolin-4(3H)-one 3l. Mp 220–222 ꢁC. 1H
NMR (DMSO-d6, 400 MHz): dH 3.85 (s, 6H, 2CH3O), 6.70–6.71 (m, 1H, ArH),
7.39 (d, J ¼ 2.0 Hz, 2H, ArH), 7.51–7.55 (m, 1H, ArH), 7.76 (d, J ¼ 7.6 Hz, 1H,
ArH), 7.82–7.86 (m, 1H, ArH), 8.16 (dd, J ¼ 8.0 Hz, J0 ¼ 1.2 Hz, 1H, ArH), 12.52
(s, 1H, NH). IR (KBr): 3180, 3068, 3022, 2963, 2936, 1675, 1616, 1589, 1496, 1463,
1439, 1421, 1337, 1305, 1263, 1186, 1161, 1062, 989, 889, 853, 834, 772 cmꢀ1. HRMS
(ESI, m=z): calcd. for C16H15N2O3 (M þ Hþ) 283.1083; found 283.1088.
2-(2-Methoxyphenyl)quinazolin-4(3H)-one 3m. Mp 210–211 ꢁC. 1H NMR
(DMSO-d6, 400 MHz): dH 3.87 (s, 3H, CH3O), 7.08–7.12 (m, 1H, ArH), 7.20
(d, J ¼ 7.6 Hz, 1H, ArH), 7.52–7.57 (m, 2H, ArH), 7.70–7.72 (m, 2H, ArH),
7.82–7.86 (m, 1H, ArH), 8.15–8.17 (m, 1H, ArH), 12.11 (s, 1H, NH). IR (KBr):
3319, 3065, 2955, 1679, 1608, 1592, 1562, 1479, 1461, 1319, 1302, 1235, 1186, 1138,
1016, 759, 745 cmꢀ1. HRMS (ESI, m=z): calcd. for C16H12N2O3Na (M þ Naþ)
275.0796; found 275.0790.
General Procedure for the Syntheses of (E)-2-Arylideneaminobenzamide
A dry 50-mL flask was charged with aromatic aldehyde (2.0 mmol), 2-amino-
benzamide, and [bmimþ][BF4ꢀ] (2 mL). The reaction mixture was stirred at room
temperature for 1–2 h and then cooled to room temperature. A small amount of
water (5 mL) was added to the mixture, and the generated yellow solid was filtered
off. The water in the filtrate was removed by distillation under reduced pressure,
and the IL in the residue was then recovered for reuse by evaporation at 80 ꢁC for
4 h in a vacuum. The crude yellow products were washed with water and purified
by recrystallization from EtOH to give 4.

SYNTHESIS OF 2-ARYLQUINAZOLIN-4(3H)-ONE DERIVATIVES
2641
Selected Data
(E)-2-(2-Chlorophenylideneamino)benzamide 4a. Mp 159–160 ꢁC. 1H
NMR (DMSO-d6, 400 MHz): dH 7.23 (d, J ¼ 8.0 Hz, 1H, ArH), 7.35–7.39 (m, 1H,
ArH), 7.51–7.64 (m, 5H, ArH þ NH), 7.82–7.84 (m, 1H, ArH), 7.99 (s, 1H, NH),
8.15–8.17 (m, 1H, ArH), 8.81 (s, 1H, CH). IR (KBr): 3405, 3256, 3057, 1621,
1587, 1563, 1480, 1448, 1435, 1385, 1364, 1277, 1189, 1159, 1049, 1034, 978, 888,
864, 770, 715 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H12ClN2O (M þ Hþ)
259.0638; found 259.0636.
(E)-2-(4-Chlorophenylideneamino)benzamide 4b. Mp 163–165 ꢁC. 1H
NMR (DMSO-d6, 400 MHz): dH 7.23 (d, J ¼ 8.0 Hz, 1H, ArH), 7.34–7.37 (m, 1H,
ArH), 7.53–7.57 (m, 1H, ArH), 7.64 (d, J ¼ 8.4 Hz, 3H, ArH þ NH), 7.89–7.91 (m,
1H, ArH), 7.98 (d, J ¼ 8.4 Hz, 2H, ArH), 8.12 (s, 1H, NH), 8.61 (s, 1H, CH). IR
(KBr): 3339, 3171, 1664, 1589, 1488, 1446, 1370, 1284, 1188, 1168, 1084, 1012,
893, 868, 822, 768 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H12ClN2O (M þ Hþ)
259.0638; found 259.0647.
(E)-2-(3-Chlorophenylideneamino)benzamide 4c. Mp 159–160 ꢁC. 1H
NMR (DMSO-d6, 400 MHz): dH 7.23 (d, J ¼ 8.0 Hz, 1H, ArH), 7.34–7.38 (m, 1H,
ArH), 7.52–7.60 (m, 2H, ArH), 7.72 (s, 1H, NH), 7.86–7.95 (m, 3H, ArH), 8.01 (s,
1H, ArH), 8.15 (s, 1H, NH), 8.60 (s, 1H, CH). IR (KBr): 3346, 3152, 1670, 1563,
1478, 1448, 1385, 1270, 1223, 1153, 1074, 1043, 969, 889, 847, 801, 773, 755 cmꢀ1
HRMS (ESI, m=z): calcd. for C14H12ClN2O (M þ Hþ) 259.0638; found 259.0622.
.
(E)-2-(3-Nitrophenylideneamino)benzamide 4d. Mp 180–181 ꢁC. 1H
NMR (DMSO-d6, 400 MHz): dH 7.26 (d, J ¼ 8.0 Hz, 1H, ArH), 7.35–7.39 (m, 1H,
ArH), 7.51–7.58 (m, 2H, ArH), 7.62 (s, 1H, NH), 7.82–7.90 (m, 2H, ArH), 7.97 (s,
1H, NH), 8.39–8.43 (m, 2H, ArH), 8.75 (s, 1H, ArH), 8.76 (s, 1H, CH). IR (KBr):
3336, 3145, 1669, 1589, 1525, 1447, 1387, 1353, 1270, 1188, 1155, 1086, 1074, 972,
854, 827, 813, 772, 755, 736 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H11N3NaO3
(M þ Naþ) 259.0638; found 259.0622.
(E)-2-(4-Nitrophenylideneamino)benzamide 4e. Mp 184–185 ꢁC. 1H
NMR (DMSO-d6, 400 MHz): dH 7.27 (d, J ¼ 7.6 Hz, 1H, ArH), 7.36–7.38 (m, 1H,
ArH), 7.51–7.54 (m, 1H, ArH), 7.62 (s, 1H, NH), 7.83–7.85 (m, 1H, ArH), 7.97 (s,
1H, NH), 8.21 (d, J ¼ 8.8 Hz, 2H, ArH), 8.40 (d, J ¼ 8.4 Hz, 2H, ArH), 8.75 (s,
1H, CH). IR (KBr): 3337, 3139, 1669, 1628, 1586, 1520, 1444, 1366, 1344, 1295,
1186, 1114, 1040, 976, 854, 780, 742 cmꢀ1. HRMS (ESI, m=z): calcd. for
C14H12N3O3 (M þ Hþ) 270.0879; found 270.0889.
(E)-2-(4-Fluorophenylideneamino)benzamide 4f. Mp 197–200 ꢁC. 1H
NMR (DMSO-d6, 400 MHz): dH 7.02 (d, J ¼ 8.0 Hz, 1H, ArH), 7.33–7.45 (m, 3H,
ArH), 7.53–7.57 (m, 1H, ArH), 7.63 (s, 1H, NH), 7.91 (d, J ¼ 7.2 Hz, 1H, ArH),
8.02–8.06 (m, 2H, ArH), 8.17 (s, 1H, NH), 8.61 (s, 1H, CH). IR (KBr): 3329,
3175, 3068, 1656, 1508, 1448, 1417, 1367, 1301, 1217, 1186, 1150, 1684, 1011, 985,
971, 948, 895, 870, 848, 798, 785, 766 cmꢀ1. HRMS (ESI, m=z): calcd. for
C14H12FN2O (M þ Hþ) 243.0934; found 243.0944.

2642
X.-S. WANG ET AL.
(E)-2-(4-Bromophenylideneamino)benzamide 4g. Mp 157–159 ꢁC. 1H
NMR (DMSO-d6, 400 MHz): dH 7.23 (d, J ¼ 7.6 Hz, 1H, ArH), 7.34–7.38 (m, 1H,
ArH), 7.53–7.61 (m, 1H, ArH), 7.63 (s, 1H, NH), 7.79 (d, J ¼ 8.4 Hz, 2H, ArH),
7.85–7.92 (m, 3H, ArH), 8.11 (s, 1H, NH), 8.60 (s, 1H, CH). IR (KBr): 3335,
3168, 1663, 1623, 1586, 1562, 1485, 1446, 1373, 1299, 1171, 1069, 1009, 891, 868,
819, 767 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H12BrN2O (M þ Hþ) 303.0133;
found 303.0138.
(E)-2-(2,3-Dichlorophenylideneamino)benzamide 4h. Mp 161–162 ꢁC. 1H
NMR (DMSO-d6, 400 MHz): dH 7.24 (d, J ¼ 8.0 Hz, 1H, ArH), 7.36–7.39 (m, 1H,
ArH), 7.53–7.58 (m, 3H, ArHþNH), 7.79–7.81 (m, 1H, ArH), 7.87 (d, J ¼ 8.0 Hz,
1H, ArH), 7.90 (s, 1H, NH), 8.12 (dd, J ¼ 8.0 Hz, J0 ¼ 1.2 Hz, 1H, ArH), 8.82 (s,
1H, CH). IR (KBr): 3353, 3178, 1687, 1652, 1622, 1556, 1448, 1388, 1362, 1264,
1264, 1179, 1154, 1086, 1043, 784, 770, 756, 704 cmꢀ1. HRMS (ESI, m=z):
calcd. for C14H11Cl2N2O (M þ Hþ) 293.0248; found 293.0247.
1
(E)-2-(2,4-Dichlorophenylideneamino)benzamide 4i. Mp 187–190 ꢁC. H
NMR (CDCl3, 400 MHz): dH 5.94 (s, 1H, NH) 7.07 (dd, J ¼ 7.6 Hz, J0 ¼ 0.8 Hz,
1H, ArH), 7.37–7.44 (m, 3H, ArH), 7.49 (d, J ¼ 7.6 Hz, 1H, ArH), 8.04 (d,
J ¼ 8.8 Hz, 1H, ArH), 8.32 (dd, J ¼ 8.8 Hz, J0 ¼ 1.6 Hz, 1H, ArH), 8.54 (s, 1H,
NH), 8.84 (s, 1H, CH). IR (KBr): 3334, 3138, 1671, 1580, 1481, 1470, 1448, 1388,
1293, 1262, 1189, 1138, 1098, 1048, 966, 873, 836, 788, 762 cmꢀ1. HRMS (ESI, m=
z): calcd. for C14H11Cl2N2O (M þ Hþ) 293.0248; found 293.0247.
General Procedure for the Syntheses
of 2,3-Dihydro-2-arylquinazolin-4(1H)-one
A dry 50-mL flask was charged with aromatic aldehyde (2.0 mmol), 2-
aminobenzamide, and [bmimþ][BF4ꢀ] (2 mL). The reaction mixture was stirred at
room temperature for 30–60 min and then cooled to room temperature. A small
amount of water (5 mL) was added to the mixture, and the generated yellow solid
was filtered off. The water in the filtrate was removed by distillation under reduced
pressure, and the IL in the residue was then recovered for reuse by evaporation at
80 ꢁC for 4 h in a vacuum. The crude yellow products were washed with water and
purified by recrystallization from EtOH to give 5.
Selected Data
2,3-Dihydro-2-(2-fluorophenyl)quinazolin-4(1H)-one 5a. Mp 189–193 ꢁC.
1H NMR (DMSO-d6, 400 MHz): dH 6.05 (s, 1H, CH), 6.69–6.75 (m, 2H, ArH),
7.05 (s, 1H, NH), 7.21–7.28 (m, 3H, ArH), 7.39–7.42 (m, 1H, ArH), 7.53
(t, J ¼ 7.6 Hz, 1H, ArH), 7.64 (d, J ¼ 8.0 Hz, 1H, ArH), 8.26 (s, 1H, NH). IR
(KBr):3371, 3182, 3070, 2924, 1657, 1613, 1514, 1485, 1460, 1440, 1392, 1332,
1305, 1256, 1218, 1170, 1148, 1127, 1099, 1033, 872, 837, 821, 781, 752 cmꢀ1. HRMS
(ESI, m=z): calcd. for C14H12FN2O (M þ Hþ) 243.0934; found 243.0935.
2,3-Dihydro-2-(2-chlorophenyl)quinazolin-4(1H)-one 5b. Mp 212–213 ꢁC
1
(lit.[18] 209–211 ꢁC). H NMR (DMSO-d6, 400 MHz): dH 6.14 (s, 1H, CH), 6.72 (t,

SYNTHESIS OF 2-ARYLQUINAZOLIN-4(3H)-ONE DERIVATIVES
2643
J ¼ 7.6 Hz, 1H, ArH), 6.77 (d, J ¼ 8.0 Hz, 1H, ArH), 7.03 (s, 1H, NH), 7.25–7.29 (m,
1H, ArH), 7.40–7.43 (m, 2H, ArH), 7.49–7.52 (m, 1H, ArH), 7.65–7.68 (m, 2H,
ArH), 8.23 (s, 1H, NH). IR (KBr): 3362, 3196, 3066, 3019, 2920, 1647, 1614,
1503, 1484, 1466, 1393, 1351, 1329, 1301, 1252, 1188, 1154, 1123, 1054, 1032,
823, 793, 747, 716 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H12ClN2O (M þ Hþ)
259.0638; found 259.0632.
2,3-Dihydro-2-(2,3-dichlorophenyl)quinazolin-4(1H)-one 5c. Mp > 300 ꢁC.
1H NMR (DMSO-d6, 400 MHz): dH 6.18 (s, 1H, CH), 6.71–6.77 (m, 2H, ArH), 7.10
(s, 1H, NH), 7.25–7.30 (m, 1H, ArH), 7.43 (t, J ¼ 8.0 Hz, 1H, ArH), 7.60–7.69 (m,
3H, ArH), 8.29 (s, 1H, NH). IR (KBr): 3355, 3243, 3079, 2964, 1638, 1503, 1450,
1412, 1385, 1344, 1323, 1295, 1252, 1121, 1106, 1049, 850, 821, 773, 747, 735,
710 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H10Cl2N2NaO (M þ Naþ) 315.0068;
found 315.0064.
2,3-Dihydro-2-(2,4-dichlorophenyl)quinazolin-4(1H)-one 5d. Mp > 300 ꢁC.
1H NMR (CDCl3, 400 MHz): dH 4.74 (s, 1H, NH), 6.28 (s, 1H, CH), 6.66 (d,
J ¼ 8.0 Hz, 1H, ArH), 6.72 (s, 1H, NH), 6.84–6.88 (m, 1H, ArH), 7.27–7.33 (m,
2H, ArH), 7.41 (d, J ¼ 2.0 Hz, 1H, ArH), 7.65 (d, J ¼ 8.4 Hz, 1H, ArH), 7.85 (d,
J ¼ 8.0 Hz, 1H, ArH). IR (KBr): 3339, 3187, 3063, 2906, 1670, 1611, 1592,
1565, 1485, 1451, 1376, 1345, 1298, 1237, 1150, 1102, 1052, 1009, 861, 824, 776,
757 cmꢀ1. HRMS (ESI, m=z): calcd. for C14H10Cl2N2NaO (M þ Naþ) 315.0068;
found 315.0066.
2,3-Dihydro-2-(2-nitrophenyl)quinazolin-4(1H)-one 5e. Mp 206–208 ꢁC
(lit.[18] 191–194 ꢁC). 1H NMR (DMSO-d6, 400 MHz): dH 6.35 (s, 1H, CH),
6.71–7.75 (m, 1H, ArH), 6.78 (d, J ¼ 8.0 Hz, 1H, ArH), 7.01 (s, 1H, NH),
7.25–7.29 (m, 1H, ArH), 7.61–7.68 (m, 2H, ArH), 7.78–7.82 (m, 1H, ArH),
7.86–7.88 (m, 1H, ArH), 8.07 (dd, J ¼ 8.4 Hz, J0 ¼ 1.2 Hz, 1H, ArH), 8.22 (s, 1H,
NH). IR (KBr): 3410, 3185, 3071, 2925, 1659, 1610, 1579, 1538, 1506, 1453, 1433,
1392, 1351, 1333, 1298, 1258, 1175, 1130, 890, 861, 826, 755, 741 cmꢀ1. HRMS
(ESI, m=z): calcd. for C14H12N3O3 (M þ Hþ) 270.0879; found 270.0879.
2,3-Dihydro-2-(2-bromophenyl)quinazolin-4(1H)-one 5f. Mp 193–194 ꢁC.
1H NMR (DMSO-d6, 400 MHz): dH 6.11 (s, 1H, CH), 6.71–7.75 (m, 1H, ArH),
6.78 (d, J ¼ 8.4 Hz, 1H, ArH), 7.01 (s, 1H, NH), 7.26–7.29 (m, 1H, ArH),
7.32–7.36 (m, 1H, ArH), 7.44–7.48 (m, 1H, ArH), 7.66–7.70 (m, 3H, ArH), 8.22
(s, 1H, NH). IR (KBr): 3366, 3190, 3063, 2927, 1656, 1613, 1503, 1485, 1450,
1394, 1351, 1329, 1254, 1188, 1156, 1125, 1026, 821, 792, 748, 713 cmꢀ1. HRMS
(ESI, m=z): calcd. for C14H12BrN2O (M þ Hþ) 303.0133; found 303.0136.
2,3-Dihydro-2-(2-methoxyphenyl)quinazolin-4(1H)-one 5g. Mp 174–175 ꢁC
1
(lit.[19] 163–165 ꢁC). H NMR (DMSO-d6, 400 MHz): dH 3.84 (s, 3H, CH3O), 6.03
(s, 1H, CH), 6.67 (t, J ¼ 7.6 Hz, 1H, ArH), 6.77 (d, J ¼ 8.4 Hz, 1H, ArH), 6.80 (s,
1H, NH), 6.95 (t, J ¼ 7.6 Hz, 1H, ArH), 7.05 (d, J ¼ 8.4 Hz, 1H, NH), 7.21–7.25
(m, 1H, ArH), 7.31–7.35 (m, 1H, ArH), 7.39–7.41 (m, 1H, ArH), 7.63 (d, J ¼ 7.6 Hz,
Hz, 1H, ArH), 8.02 (s, 1H, NH). IR (KBr): 3390, 3317, 3191, 3051, 2933, 1663, 1610,
1504, 1488, 1465, 1388, 1330, 1280, 1242, 1187, 1165, 1151, 1111, 1027, 857, 827, 753,

2644
X.-S. WANG ET AL.
716 cmꢀ1. HRMS (ESI, m=z): calcd. for C15H15N2O2 (M þ Hþ) 255.1143; found
255.1134.
2,3-Dihydro-2-(2,3-dimethoxyphenyl)quinazolin-4(1H)-one 5h. Mp 238–
240 ꢁC (lit.[19] 232–233 ꢁC). 1H NMR (DMSO-d6, 400 MHz): dH 3.79 (s, 3H,
CH3O), 3.82 (s, 3H, CH3O), 6.03 (s, 1H, CH), 6.66–6.70 (m, 1H, ArH), 6.74 (d,
J ¼ 8.0 Hz, 1H, ArH), 7.80 (s, 1H, NH), 7.05–7.10 (m, 3H, ArH), 7.21–7.25 (m,
1H, ArH), 7.63 (dd, J ¼ 8.0 Hz, J0 ¼ 1.6 Hz, 1H, ArH), 8.02 (s, 1H, NH). IR
(KBr): 3355, 3204, 3073, 3015, 2960, 2931, 1649, 1615, 1504, 1484, 1428, 1388,
1328, 1302, 1274, 1254, 1224, 1171, 1123, 1077, 1032, 1003, 777, 754, 715 cmꢀ1
HRMS (ESI, m=z): calcd. for C16H17N2O3 (M þ Hþ) 285.1293, found 285.1232.
.
ACKNOWLEDGMENTS
We are grateful to the National Natural Science Foundation of China
(20802061), the Natural Science Foundation (08KJD150019), and the Qing Lan
Project (08QLT001) of Jiangsu Education Committee for financial support.
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