New efficient synthesis of 1,2,4-trisubstituted imidazoles and imidazo[1,2-c]quinazolines by a tandem aza-Wittig/electrocyclic ring-closure process

Article abstract of DOI:10.1016/j.tet.2011.12.005

A series of 1,2,4-trisubstituted imidazoles 5 were synthesized efficiently by a tandem aza-Wittig/1,5-electrocyclic ring-closure reaction of vinyliminophosphoranes 3 with aldehydes. Reactions of 5s,t with triphenylphosphine produced iminophosphoranes 7. A tandem aza-Wittig reaction of iminophosphorane 7 with isocyanate generated imidazo[1,2-c]quinazolines 9 in high yields.

Full text of DOI:10.1016/j.tet.2011.12.005

Tetrahedron 68 (2012) 965e971
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New efficient synthesis of 1,2,4-trisubstituted imidazoles and imidazo[1,2-c]
quinazolines by a tandem aza-Wittig/electrocyclic ring-closure process
*
Yi-Bo Nie, Zhuan Duan, Ming-Wu Ding
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Central China Normal University, LuoYu Road 100, Wuhan 430079, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 October 2011
Received in revised form 20 November 2011
Accepted 2 December 2011
Available online 8 December 2011
A series of 1,2,4-trisubstituted imidazoles 5 were synthesized efficiently by a tandem aza-Wittig/1,5-
electrocyclic ring-closure reaction of vinyliminophosphoranes 3 with aldehydes. Reactions of 5s,t with
triphenylphosphine produced iminophosphoranes 7. A tandem aza-Wittig reaction of iminophosphorane
7 with isocyanate generated imidazo[1,2-c]quinazolines 9 in high yields.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
have recently been interested in the synthesis of various het-
erocycles through aza-Wittig reactions.20 Here we wish to report
Imidazoles are important heterocycles bearing good biological
and pharmaceutical activities and have attracted the attention of
synthetic chemists for many years.1 A wide variety of imidazole
derivatives have been used as antitumor agents,2 heme oxygenase
inhibitors,3 B-Raf kinase inhibitors,4 plant growth regulators,5 and
pesticides.6 The imidazole ring system is also a component of some
natural products, such as isonaamine A, dorimidazole A, and pre-
clathridine A.7 The structural diversity and complexity of naturally
occurring imidazoles have generated much interest in the de-
velopment of efficient methods for their synthesis. There are many
methods reported for the synthesis of imidazoles,8 however, only
a few were known for the synthesis of 1,2,4-trisubstituted imid-
azoles. For example, some 1,2,4-trisubstituted imidazoles were
a new efficient synthesis of 1,2,4-trisubstituted imidazoles and
imidazo[1,2-c]quinazolines via the tandem aza-Wittig/
electrocyclic ring-closure process, from easily accessible starting
materials.
2. Results and discussion
The
a,b
a-azidocinnamaldehyde 1, obtained from the reaction
of
-dibromocinnamaldehyde with sodium azide,21 reacted
with amine in the presence of acetic acid to give the azide 2 in
79e92% yields. Further Staudinger reaction of azides 2 with tri-
phenylphosphine (R¼Ph) or methyldiphenylphosphine (R¼Me) at
room temperature produced iminophosphorane 3 in high yields
(Scheme 1).
recently prepared from the reaction of N-alkyl-N-(b-keto)amide
with NH4OAc,9 the cyclization of some thioamides obtained from
amino acid esters,10 and the palladium-catalyzed cyclization of the
O-pentafluorobenzoylamidoximes.11
R1
CHO
R1NH2
HOAc
Ph
Ph
Ph
N
The aza-Wittig reactions of iminophosphoranes have received
increasing attention in view of their utility in the synthesis of
nitrogen-containing heterocyclic compounds.12 The carbodii-
mides or aldimines, obtained efficiently by aza-Wittig reaction of
iminophosphoranes with isocyanates or aldehydes under mild
neutral condition, can be used as synthetic intermediates of
heterocycles by tandem processes involving aza-Wittig/
intramolecular electrocyclic ring closure. This tandem process
has been utilized previously in synthesis of many heterocycles,
such as pyridines,13 isoquinolines,14 benzo[b]thieno[2,3-b]pyri-
dines,15 pyrido[30,20:4,5]thieno[3,2-d]pyrimidine,16 pyrido[1,2-c]
pyrimidine,17 quinazolines,18 and imidazo[1,5-a]pyridines.19 We
N3
N3
2
1
R1
Ph2PR
N
N=PPh2R
3
Scheme 1. Preparation of vinyliminophosphoranes 3.
Initially, we selected the triphenyliminophosphorane 3a and
benzaldehyde as the reactants (Scheme 2, Table 1). When the tri-
phenyliminophosphorane 3a and benzaldehyde was stirred in
ethanol at room temperature for 24 h, no product was detected by
TLC detection (Table 1, entry 1). However, imidazole derivative 5a
* Corresponding author. Tel.: þ86 27 63158845; fax: þ86 27 67862041; e-mail
address: ding5229@yahoo.com.cn (M.-W. Ding).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.12.005

966
Y.-B. Nie et al. / Tetrahedron 68 (2012) 965e971
was directly obtained as the reaction was carried out at 50 ꢀC or
80 ꢀC for 24 h with 29% or 62% yields (Table 1, entries 2 and 3). The
expected aza-Wittig product 4a might produced but cyclized
quickly to give imidazole 5a under the reaction condition. When
more reactive methyldiphenyl iminophosphorane 3b was used as
the reactant, the reaction took place even at room temperature for
24 h and the imidazole 5a was obtained in 72% yield (Table 1, entry
4). At higher temperature (80 ꢀC), the same reaction occurred
smoothly to give 5a in 85% yield with only 3 h (Table 1, entry 5).
Table 2
Preparation of imidazoles 5 from methyldiphenyl iminophosphorane 3 (R¼Me)
R1
R2
Condition
Yielda (%)
5a
5b
5c
5d
5e
5f
5g
5h
5i
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-Cl-C6H4
4-F-C6H4
Furan-2-yl
n-C3H7
3-NO2eC6H4
4-CH3OeC6H4
Ph
2-CH3OeC6H4
4-CleC6H4
4-CleC6H4
2,4-2ClePh
O
80 ꢀC/3 h
80 ꢀC/3 h
80 ꢀC/4 h
80 ꢀC/5 h
80 ꢀC/3 h
80 ꢀC/4 h
80 ꢀC/3 h
80 ꢀC/4 h
80 ꢀC/3 h
80 ꢀC/3 h
80 ꢀC/3 h
85
82
72
63
58
81
83
80
84
91
87
Benzyl
4-CleC6H4
4-CleC6H4
5j
5k
Ph
Ph
N
Ph
PhCHO
Ph
N
N
5l
4-CleC6H4
80 ꢀC/4 h
75
N=PPh2R
O
Ph
4a
3a,b
5m
5n
5o
5p
5q
5r
4-CleC6H4
4-CleC6H4
4-CleC6H4
4-CleC6H4
4-CleC6H4
2-CH3eC6H4
4-CleC6H4
Ph
4-NO2eC6H4
Ph
80 ꢀC/3 h
80 ꢀC/3 h
80 ꢀC/4 h
80 ꢀC/3 h
80 ꢀC/3 h
80 ꢀC/3 h
rt/24 h
69
82
81
83
82
76
65
60
Ph
4-CH3OeC6H4
4-BreC6H4
4-FeC6H4
4-CleC6H4
2-N3eC6H4
2-N3eC6H4
N
Ph
N
Ph
5s
5t
5a
rt/24 h
Scheme 2. Preparation of compounds 5a.
a
Isolated yields based on iminophosphorane 3 (R¼Me).
Table 1
Optimization of the reaction conditions
were further treated with aromatic isocyanate at room tempera-
ture, the color of the reaction mixture quickly turned red, and
imidazo[1,2-c]quinazolines 9 were isolated as orange to red crys-
talline solids in good yields (Table 3, Scheme 4). Presumably, the
conversion of 7 into 9 involves initial aza-Wittig reaction between
the iminophosphorane 7 and the isocyanate to give a carbodiimide
8 as highly reactive intermediate, which easily undergoes 1,6-
electrocyclic ring closure to give the imidazo[1,2-c]quinazolines 9.
It is noteworthy that the reaction can be easily carried out at room
temperature under mild neutral condition.
Entry
R
Condition
Yielda (%)
1
2
3
4
5
Ph
Ph
Ph
Me
Me
rt/24 h
0
29
62
72
85
50 ꢀC/24 h
80 ꢀC/24 h
rt/24 h
80 ꢀC/3 h
a
Isolated yields of 5a based on iminophosphorane 3.
With the optimized condition, various methyldiphenyl imino-
phosphorane 3 and aldehydes were employed for the reaction
(Scheme 3). All reactions proceeded smoothly to give the corre-
sponding imidazoles 5 (Table 2) in 58e91% yields. When various
aromatic or aliphatic aldehydes were used, the reaction produced
imidazoles 5 in moderate to good yields at 80 ꢀC for 3e5 h. How-
ever, as the thermal labile 2-azidobenzaldehyde was utilized, the
best yields of the products 5s,t were obtained when the reaction
was carried out at room temperature (Table 2). The formation of the
imidazoles 5 can be rationalized in terms of an initial aza-Wittig
reaction to give the imine 4, which undergoes 1,5-electrocyclic
ring-closure to give 5 through intermediate 6.19,22
Ph
Ph
PPh3
N
N
N3
N
R3NCO
Ph3P
N
N
R1
R1
7
5s,t
NR3
N
NR3
Ph
Ph
C
N
N
N
N
N
R1
R1
R1
R1
R2CHO
Ph
N
Ph
N
N
9
N=PPh2Me
8
R2
Scheme 4. Preparation of imidazo[1,2-c]quinazolines 9.
3
4
Table 3
Ph
Preparation of imidazo[1,2-c]quinazolines 9
Ph
N
N+ R1
R2
N-
R1
R3
Yielda (%)
R2
N
9a
9b
9c
9d
9e
9f
9g
9h
9i
4-CleC6H4
4-CleC6H4
Ph
Ph
Ph
4-CleC6H4
4-CleC6H4
4-CleC6H4
Ph
4-CleC6H4
4-CH3eC6H4
4-CleC6H4
4-CH3eC6H4
3-CH3eC6H4
3-CH3eC6H4
Ph
i-Pr
4-FeC6H4
Ph
93
84
84
83
90
92
85
91
81
82
R1
H
5
6
Scheme 3. Preparation of imidazoles 5.
The obtained 2-(2-azidophenyl)imidazoles 5s,t were further
treated with triphenylphosphine, and the iminophosphorane 7 was
obtained in high yield via Staudinger reaction (Scheme 4). When
solutions of iminophosphoranes 7 in dry methylene dichloride
9j
Ph
a
Isolated yields of 9 based on iminophosphorane 7.

Y.-B. Nie et al. / Tetrahedron 68 (2012) 965e971
967
3. Conclusion
694; 1H NMR (CDCl3, 600 MHz):
d
8.09 (s, 1H, N]CH), 7.85 (d,
J¼6.6 Hz, 2H, AreH), 7.41e6.96 (m, 7H, AreH), 6.18 (s, 1H, ]CH),
We have developed a new and efficient synthesis of unreported
1,2,4-substituted imidazoles and imidazo[1,2-c]quinazolines via
aza-Wittig/electrocyclic ring-closure reaction from vinyl-
iminophosphorane. This method utilizes easily accessible starting
material and allows mild reaction conditions, straightforward
product isolation and good yields. It has the potential in synthesis
of various 1,2,4-trisubstituted or fused imidazoles, which are of
considerable interest as potential biological active compounds or
pharmaceuticals.
2.38 (s, 3H, CH3). 13C NMR (CDCl3, 150 MHz):
d
155.8, 148.8, 134.1,
133.5, 133.4, 130.5, 130.0, 129.8, 128.8, 128.4, 127.9, 126.6, 116.9, 18.3.
Anal. Calcd for C16H14N4: C, 73.26; H, 5.38; N, 21.36. Found: C, 72.98;
H, 5.51; N, 21.62.
4.3. Synthesis of iminophosphoranes 3
4.3.1. N-(3-Phenyl-2-((triphenylphosphoranylidene)amino)
allyli-
4. Experimental
4.1. General
dene)aniline (3a). A solution of triphenylphosphine (0.52 g,
2 mmol) in dry methylene dichloride (10 mL) was added dropwise
at room temperature to a well-stirred solution of azide 2a (0.50 g,
2 mmol) in dry methylene dichloride (10 mL). The reaction mixture
was stirred at room temperature for 4 h; then the solvent was re-
moved under reduced pressure. The residue was recrystallized
from ethanol/petroleum ether (1:2) to give iminophosphoranes 3a
(0.88 g, 91%) as yellow solid. Mp: 151e153 ꢀC, 1H NMR (CDCl3,
Melting points were determined using an X-4 model apparatus
and were uncorrected. MS were measured on a Finnigan Trace MS
spectrometer. IR was recorded on a PE-983 infrared spectrometer
as KBr pellets with absorption in cmꢁ1. NMR was recorded in CDCl3
or DMSO-d6 on a Varian Mercury 400 or 600 spectrometer and
resonances relative to TMS. Elementary analyses were taken on
a Vario EL III elementary analysis instrument.
600 MHz):
and N]CH), 6.19 (d, J¼7.8 Hz, 2H, AreH), 6.02 (d, J¼7.2 Hz, 1H, ]
CH). 13C NMR (CDCl3, 150 MHz):
161.0, 150.4, 145.6, 138.8, 135.2,
d
8.25 (d, J¼7.2 Hz, 2H, AreH), 7.76e6.98 (m, 22H, AreH
d
134.5, 132.6, 132.1, 131.9, 130.3, 128.9, 128.5, 127.8, 125.5, 124.6,
123.2, 120.0. Anal. Calcd for C33H27N2P: C, 82.14; H, 5.64; N, 5.81.
Found: C, 82.38; H, 5.79; N, 5.62.
4.2. Synthesis of azides 2
4.2.1. (2-Azido-3-phenylallylidene)benzenamine
(2a). a-Azido-
cinnamaldehyde 1 (0.35 g, 2 mmol) was added to a solution of
aniline (0.19 g, 2 mmol) in methanol (15 mL) with two drops of
acetic acid. The reaction mixture was stirred at ambient tempera-
ture for 3e4 h until a solid precipitated. The solid formed was fil-
tered off and recrystallized from ethanol/petroleum ether (1:1) to
give 0.44 g (89%) of azide 2a as light yellow solid. Mp: 85e87 ꢀC, IR
(KBr, cmꢁ1): 2140, 1637, 1592, 1497, 1458, 1421, 1368, 1332, 1309,
4.3.2. N-(2-((Methyldiphenylphosphoranylidene)amino)-3-
phenylallylidene)aniline
(3b). A
solution
of
methyl-
diphenylphosphine (0.40 g, 2 mmol) in dry methylene dichloride
(10 mL) was added dropwise at room temperature to a well-stirred
solution of azide 2a (0.50 g, 2 mmol) in dry methylene dichloride
(10 mL). The reaction mixture was stirred at room temperature for
4 h, then the solvent was removed under reduced pressure. The
residue was purified by column chromatography on silica gel with
petroleum ether/diethyl ether (6:1, v/v) as eluent to give 3b (0.72 g,
86%) as yellow solid. Mp: 144e145 ꢀC, 1H NMR (CDCl3, 600 MHz):
1276, 1187, 1086, 976, 784, 713. 1H NMR (CDCl3, 600 MHz):
1H, N]CH), 7.84 (d, J¼6.6 Hz, 2H, AreH), 7.40e7.20 (m, 8H, AreH),
6.17 (s, 1H, ]CH). 13C NMR (CDCl3, 150 MHz):
156.4, 149.7, 134.1,
d 8.13 (s,
d
132.9, 130.0, 129.8, 129.1, 128.8, 128.4, 128.2, 126.5, 120.9. Anal.
Calcd for C15H12N4: C, 72.56; H, 4.87; N, 22.57. Found: C, 72.36; H,
4.98; N, 22.71.
d
8.25 (d, J¼7.8 Hz, 2H, AreH), 7.80e7.05 (m, 17H, AreH and N]CH),
6.48 (d, J¼7.8 Hz, 2H, AreH), 6.01 (d, J¼7.8 Hz, 1H, ]CH), 2.30 (d,
2JPeH¼13.2 Hz, 3H, CH3). 13C NMR (CDCl3, 150 MHz):
d 162.1, 150.8,
145.9, 138.8, 136.5, 135.8, 130.4, 130.3, 129.2, 128.9, 128.7, 128.2, 127.8,
125.5, 124.8, 123.2, 123.1, 120.2, 19.5, 19.1. Anal. Calcd for C28H25N2P:
C, 79.98; H, 5.99; N, 6.66. Found: C, 79.89; H, 6.07; N, 6.96.
4.2.2. (2-Azido-3-phenylallylidene)-1-phenylmethanamine
(2b). Operation as above with phenylmethanamine (0.21 g,
2 mmol), compound 2b (0.41 g, 79%) was also isolated as light
yellow solid. Mp: 158e160 ꢀC, IR (KBr, cmꢁ1): 3063, 3028, 2110,
1681, 1636, 1494, 1450, 1394, 1340, 1300, 1262, 1048, 1028, 877, 731.
4.3.3. 4-Chloro-N-(2-((methyldiphenylphosphoranylidene) amino)-
3-phenylallylidene)aniline (3c). Operation as above with azide 2c
(0.56 g, 2 mmol), compound 3c (0.84 g, 92%) was also isolated as light
1H NMR (CDCl3, 600 MHz):
d
7.77 (d, J¼7.2 Hz, 2H, AreH), 7.37e7.20
(m, 8H, AreH), 6.74 (s, 1H, ]CH), 3.99 (s, 2H, CH2). 13C NMR (CDCl3,
150 MHz): 158.8, 138.9, 134.2, 132.7, 129.8, 129.7, 128.5, 128.4,
yellow solid. Mp: 54e56 ꢀC, 1H NMR (CDCl3, 600 MHz):
d 8.24 (d,
d
J¼7.8 Hz, 2H, AreH), 7.78e7.13 (m, 16H, AreH and N]CH), 6.39 (d,
127.7, 127.0, 126.2, 64.0. Anal. Calcd for C16H14N4: C, 73.26; H, 5.38;
N, 21.36. Found: C, 72.98; H, 5.51; N, 21.12.
J¼8.4 Hz, 2H, AreH), 6.01 (d, J¼7.2 Hz, 1H, ]CH), 2.28 (d,
2JPeH¼12.6 Hz, 3H, CH3). 13C NMR (CDCl3, 150 MHz):
d 162.5, 149.3,
145.8, 138.7, 136.4, 135.7, 130.4, 130.3, 130.2, 129.0, 128.9, 128.8, 128.3,
128.2, 127.9, 125.8, 124.0, 123.8, 121.5, 19.5, 19.0. Anal. Calcd for
C28H24ClN2P: C, 73.92; H, 5.32;N, 6.16. Found: C, 73.79;H, 5.41;N, 6.07.
4.2.3. (2-Azido-3-phenylallylidene)-4-chloroaniline (2c). Operation
as above with 4-chloroaniline (0.26 g, 2 mmol), compound 2c (0.52 g,
92%) was also isolated as light yellow solid. Mp: 111e113 ꢀC, IR (KBr,
cmꢁ1): 2161, 2112,1611,1483,1446,1392,1354,1260,1165,1090,1009,
4.3.4. 2-Methyl-N-(2-((methyldiphenylphosphoranylidene) amino)-
3-phenylallylidene)aniline (3d). Operation as above with azide 2d
(0.52 g, 2 mmol), compound 3d (0.78 g, 90%) was also isolated as
829, 760, 693. 1H NMR (CDCl3, 600 MHz):
d 8.09 (s, 1H, N]CH), 7.83
(d, J¼7.8Hz, 2H, AreH), 7.41e7.13 (m, 7H, AreH), 6.18 (s,1H, ]CH).13C
NMR (CDCl3,150 MHz):
d
156.7, 148.1, 134.0, 132.8, 132.2, 130.0, 129.3,
light yellow solid. Mp: 38e40 ꢀC, 1H NMR (CDCl3, 600 MHz):
d 8.23
129.0,128.8,128.5,122.3. Anal. Calcd for C15H11ClN4: C, 63.72; H, 3.92;
N, 19.82. Found: C, 63.57; H, 3.78; N, 20.02.
(d, J¼7.8 Hz, 2H, AreH), 7.76e6.93 (m, 16H, AreH and N]CH), 6.17
(d, J¼7.8 Hz, 1H, AreH), 5.98 (d, J¼7.2 Hz, 1H, ]CH), 2.31 (d,
2JPeH¼13.2 Hz, 3H, CH3), 1.64 (s, 3H, CH3). 13C NMR (CDCl3,
4.2.4. (2-Azido-3-phenylallylidene)-2-methylaniline (2d). Operation
as above with o-toluidine (0.21 g, 2 mmol), compound 2d (0.43 g,
83%) was also isolated as light yellow solid. Mp: 141e143 ꢀC, IR (KBr,
cmꢁ1): 2157, 2109, 1612, 1588, 1447, 1386, 1353, 1261, 1100, 758,
150 MHz): d 163.7, 151.4, 145.7, 138.7, 136.0, 135.4, 130.6, 130.4,
129.9, 129.2, 128.9, 128.3, 128.2, 127.8, 126.2, 125.6, 124.1, 123.6,
123.4, 119.0, 19.5, 19.0, 17.3. Anal. Calcd for C29H27N2P: C, 80.16; H,
6.26; N, 6.45. Found: C, 80.31; H, 6.15; N, 6.72.

968
Y.-B. Nie et al. / Tetrahedron 68 (2012) 965e971
4.4. Synthesis of imidazoles 5
12H, AreH), 6.77 (d, J¼9.0 Hz, 2H, AreH), 6.64 (s, 1H, imidazole-5-
H), 4.05 (s, 2H, CH2), 3.77 (s, 3H, OCH3). 13C NMR (CDCl3, 150 MHz):
159.4, 145.9, 141.9, 139.7, 138.5, 129.9, 129.2, 129.0, 128.3, 127.6,
126.0, 125.6, 122.8, 119.3, 113.4, 55.0, 35.0. MS (EI, 70 eV) m/z: 340
(Mþ, 69), 249 (38), 210 (100), 146 (17), 130 (16), 103 (16), 91 (15), 77
(60). Anal. Calcd for C23H20N2O: C, 81.15; H, 5.92; N, 8.23. Found: C,
81.37; H, 6.08; N, 8.41.
4.4.1. 4-Benzyl-2-(4-chlorophenyl)-1-phenyl-1H-imidazole (5a). 4-
Chlorobenzaldehyde (0.28 g, 2 mmol) was added to a solution of
iminophosphorane 3b (0.69 g, 2 mmol) in ethanol (15 mL). The
solution was then heated at reflux for 3 h. After the reaction was
completed, the solvent was evaporated and the residue was puri-
fied by column chromatography to give 5a (0.59 g, 85%) as white
d
solid. Mp: 171e173 ꢀC, 1H NMR (CDCl3, 600 MHz):
14H, AreH), 6.69 (s, 1H, imidazole-5-H), 4.04 (s, 2H, CH2). 13C NMR
(CDCl3, 150 MHz): 144.8, 142.4, 139.5, 138.1, 134.1, 129.7, 129.4,
d
7.39e7.14 (m,
4.4.7. 4-Benzyl-1,2-diphenyl-1H-imidazole (5g). Operation as above
with benzaldehyde (0.21 g, 2 mmol), compound 5g (0.51 g, 83%)
was also isolated as white solid. Mp: 120e122 ꢀC, 1H NMR (CDCl3,
d
128.9, 128.6, 128.3, 128.2, 128.0, 126.1, 125.6, 120.0, 34.9. MS (EI,
70 eV) m/z: 344 (Mþ, 46), 214 (100), 206 (14), 103 (14), 94 (10), 77
(45). Anal. Calcd for C22H17ClN2: C, 76.63; H, 4.97; N, 8.12. Found: C,
76.48; H, 5.17; N, 8.40.
600 MHz):
d
7.40e7.16 (m, 15H, AreH), 6.69 (s, 1H, imidazole-5-H),
146.0, 142.3, 139.7,
4.06 (s, 2H, CH2). 13C NMR (CDCl3, 150 MHz):
d
138.4, 130.2, 129.2, 129.0, 128.6, 128.3, 128.1, 128.0, 125.7, 125.5,
119.8, 119.7, 35.0. MS (EI, 70 eV) m/z: 310 (Mþ, 47), 206 (12), 180
(100), 103 (12), 77 (38). Anal. Calcd for C22H18N2: C, 85.13; H, 5.85;
N, 9.03. Found: C, 85.34; H, 5.65; N, 9.32.
4.4.2. 4-Benzyl-2-(4-fluorophenyl)-1-phenyl-1H-imidazole
(5b). Operation as above with 4-fluorobenzaldehyde (0.25 g,
2 mmol), compound 5b (0.54 g, 82%) was also isolated as white
4.4.8. 4-Benzyl-2-(2-methoxyphenyl)-1-phenyl-1H-imidazole
(5h). Operation as above with 2-methoxybenzaldehyde (0.27 g,
2 mmol), compound 5h (0.54 g, 80%) was also isolated as light
solid. Mp: 83e85 ꢀC, 1H NMR (CDCl3, 600 MHz):
d
7.38e6.93 (m,
14H, AreH), 6.68 (s, 1H, imidazole-5-H), 4.04 (s, 2H, CH2). 13C NMR
(CDCl3, 150 MHz): 163.2, 161.6, 145.0, 142.2, 139.6, 138.2, 130.4,
d
yellow oil. 1H NMR (CDCl3, 600 MHz):
d
7.60e6.99 (m, 13H, AreH),
6.74 (s, 1H, imidazole-5-H), 6.69 (d, J¼8.4 Hz, 1H, AreH), 4.06 (s, 2H,
CH2), 3.24 (s, 3H, OCH3). 13C NMR (CDCl3, 150 MHz):
156.5, 144.1,
129.2, 128.9, 128.3, 127.8, 126.4, 126.0, 125.5, 119.7, 115.1, 115.0, 34.9.
MS (EI, 70 eV) m/z: 328 (Mþ, 50), 208 (14), 198 (100), 180 (10), 104
(10), 94 (23), 77 (46). Anal. Calcd for C22H17FN2: C, 80.47; H, 5.22; N,
8.53. Found: C, 80.64; H, 5.07; N, 8.82.
d
142.3, 140.0, 139.2, 131.9, 130.5, 129.1, 128.7, 128.4, 126.8, 126.1,
123.7, 120.7, 120.4, 118.2, 110.8, 54.5, 35.2. MS (EI, 70 eV) m/z: 340
(Mþ, 100), 309 (27), 248 (12), 210 (44), 206 (16), 130 (16), 104 (16),
91 (35), 77 (60). Anal. Calcd for C23H20N2O: C, 81.15; H, 5.92; N, 8.23.
Found: C, 81.36; H, 6.13; N, 8.57.
4.4.3. 4-Benzyl-2-(furan-2-yl)-1-phenyl-1H-imidazole
(5c). Operation as above with furan-2-carbaldehyde (0.19 g,
2 mmol), compound 5c (0.43 g, 72%) was also isolated as white
solid. Mp: 82e84 ꢀC, 1H NMR (CDCl3, 600 MHz):
d
7.42e7.21 (m,
11H, AreH), 6.60 (s, 1H, imidazole-5-H), 6.28e5.99 (m, 2H, AreH),
4.05 (s, 2H, CH2). 13C NMR (CDCl3, 150 MHz):
144.6, 142.6, 142.5,
4.4.9. 1,4-Dibenzyl-2-(4-chlorophenyl)-1H-imidazole (5i). A solu-
tion of methyldiphenylphosphine (0.40 g, 2 mmol) in dry methy-
lene dichloride (10 mL) was added dropwise at room temperature
to a well-stirred solution of azide 2b (0.52 g, 2 mmol) in dry
methylene dichloride (10 mL). After stirring for 4 h, the solvent was
removed under reduced pressure. Then 4-chlorobenzaldehyde
(0.28 g, 2 mmol) and 15 mL ethanol was added to the mixture.
The solution was then heated at reflux for 3 h. The solvent was
evaporated and the residue was purified by column chromatogra-
phy to give compound 5i (0.60 g, 84%) as white solid. Mp:
d
139.6, 138.6, 137.9, 129.2, 128.9, 128.6, 128.3, 126.3, 126.1, 119.5,
110.9, 108.9, 34.9. MS (EI, 70 eV) m/z: 300 (Mþ, 60), 208 (16), 170
(100), 102 (8) 94 (19), 77 (46). Anal. Calcd for C20H16N2O: C, 79.98;
H, 5.37; N, 9.33. Found: C, 80.25; H, 5.63; N, 9.42.
4.4.4. 4-Benzyl-1-phenyl-2-propyl-1H-imidazole (5d). Operation as
above with butyraldehyde (0.15 g, 2 mmol), compound 5d (0.35 g,
63%) was also isolated as light yellow oil. 1H NMR (CDCl3, 600 MHz):
115e117 ꢀC, 1H NMR (CDCl3, 600 MHz):
6.56 (s, 1H, imidazole-5-H), 5.10 (s, 2H, CH2), 3.99 (s, 2H, CH2). 13
NMR (CDCl3, 150 MHz): 146.4, 142.1, 139.8, 136.7, 134.6, 129.8,
128.8, 128.7, 128.6, 128.2, 127.7, 126.1, 125.9, 118.6, 50.0, 35.0. MS (EI,
70 eV) m/z: 358 (Mþ, 23), 248 (7), 208 (8), 103 (12), 91 (100). Anal.
Calcd for C23H19ClN2: C, 76.98; H, 5.34; N, 7.81. Found: C, 76.86; H,
5.52; N, 8.09.
d 7.47e7.03 (m, 14H, AreH),
d
7.43e7.20 (m, 10H, AreH), 6.49 (s, 1H, imidazole-5-H), 3.97 (s, 2H,
C
CH2), 2.60 (t, J¼7.8 Hz, 2H, CH2), 1.68e1.62 (m, 2H, CH2), 0.87 (t,
d
J¼7.2 Hz, 3H, CH3). 13C NMR (CDCl3, 150 MHz):
d
148.0, 140.7, 139.9,
137.9, 129.3, 128.9, 128.3, 128.0, 126.0, 125.8, 117.5, 34.9, 29.0, 21.8,
13.8. MS (EI, 70 eV) m/z: 276 (Mþ, 44), 248 (100), 206 (12), 172 (20),
146 (52), 103 (22), 91 (27), 77 (53). Anal. Calcd for C19H20N2: C,
82.57; H, 7.29; N, 10.14. Found: C, 82.86; H, 7.35; N, 10.02.
4.4.10. 4-Benzyl-1,2-bis(4-chlorophenyl)-1H-imidazole
(5j). Operation as above with iminophosphorane 3c (0.90 g,
2 mmol) and 4-chlorobenzaldehyde (0.28 g, 2 mmol), compound 5j
(0.69 g, 91%) was also isolated as white solid. Mp: 106e108 ꢀC, 1H
4.4.5. 4-Benzyl-2-(3-nitrophenyl)-1-phenyl-1H-imidazole
(5e). Operation as above with 3-nitrobenzaldehyde (0.30 g,
2 mmol), compound 5e (0.41 g, 58%) was also isolated as light
yellow solid. Mp: 104e105 ꢀC, 1H NMR (CDCl3, 600 MHz):
d
8.22 (s,
NMR (CDCl3, 600 MHz):
J¼8.4 Hz, 2H, AreH), 6.66 (s, 1H, imidazole-5-H), 4.03 (s, 2H, CH2).
13C NMR (CDCl3, 150 MHz):
144.8, 142.7, 139.4, 136.6, 134.3, 133.7,
d 7.37e7.23 (m, 11H, AreH), 7.08 (d,
1H, AreH), 8.11 (d, J¼6.6 Hz,1H, AreH), 7.75 (d, J¼6.6 Hz,1H, AreH),
7.41e7.19 (m, 11H, AreH), 6.77 (s, 1H, imidazole-5-H), 4.06 (s, 2H,
d
CH2). 13C NMR (CDCl3, 150 MHz):
d
147.9, 143.4, 142.9, 139.4, 137.7,
129.7, 129.5, 128.8, 128.4, 128.3, 126.7, 126.1, 119.7, 34.9. MS (EI,
70 eV) m/z: 380 (Mþ, 28), 250 (53), 248 (100), 111 (15), 77 (12),
40(27). Anal. Calcd for C22H16Cl2N2: C, 69.67; H, 4.25; N, 7.39.
Found: C, 69.57; H, 4.59; N, 7.22.
134.0, 131.8, 129.7, 129.1, 128.9, 128.6, 128.4, 126.2, 125.7, 123.1,
122.7, 120.9, 34.9. MS (EI, 70 eV) m/z: 355 (Mþ, 43), 309 (6), 225
(100), 206 (10), 179 (17), 103 (13), 91 (8), 77 (35). Anal. Calcd for
C22H17N3O: C, 74.35; H, 4.82; N, 11.82. Found: C, 74.13; H, 5.04; N,
12.05.
4.4.11. 4-Benzyl-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-im-
idazole (5k). Operation as above with iminophosphorane 3c
(0.90 g, 2 mmol) and 2,4-dichlorobenzaldehyde (0.35 g, 2 mmol),
compound 5k (0.72 g, 87%) was also isolated as white solid. Mp:
4.4.6. 4-Benzyl-2-(4-methoxyphenyl)-1-phenyl-1H-imidazole
(5f). Operation as above with 4-methoxybenzaldehyde (0.27 g,
2 mmol), compound 5f (0.55 g, 81%) was also isolated as white
124e126 ꢀC, 1H NMR (CDCl3, 600 MHz):
d
7.43e7.24 (m,10H, AreH),
solid. Mp: 112e114 ꢀC, 1H NMR (CDCl3, 600 MHz):
d 7.39e7.15 (m,
6.98 (d, J¼7.8 Hz, 2H, AreH), 6.77 (s,1H, imidazole-5-H), 4.04 (s, 2H,

Y.-B. Nie et al. / Tetrahedron 68 (2012) 965e971
969
CH2). 13C NMR (CDCl3, 150 MHz):
d
142.8, 142.6, 139.5, 136.2, 135.9,
103 (13), 77 (9). Anal. Calcd for C22H16BrClN2: C, 62.36; H, 3.81; N,
6.61. Found: C, 62.56; H, 4.03; N, 6.85.
134.8, 133.2, 129.6, 129.3, 128.9, 128.8, 128.4, 127.2, 126.2, 125.5,
118.3, 34.9. MS (EI, 70 eV) m/z: 414 (Mþ,10), 284 (100), 240 (16), 204
(11),138 (13),111 (32),103 (19), 77 (15). Anal. Calcd for C22H15Cl3N2:
C, 63.87; H, 3.65; N, 6.77. Found: C, 64.06; H, 3.73; N, 6.92.
4.4.17. 4-Benzyl-1-(4-chlorophenyl)-2-(4-fluorophenyl)-1H-imidaz-
ole (5q). Operation as above with iminophosphorane 3c (0.90 g,
2 mmol) and 4-fluorobenzaldehyde (0.37 g, 2 mmol), compound 5q
(0.59 g, 82%) was also isolated as white solid. Mp: 79e81 ꢀC, 1H
4.4.12. 2-(Benzo[d][1,3]dioxol-5-yl)-4-benzyl-1-(4-chlorophenyl)-
1H-imidazole (5l). Operation as above with iminophosphorane 3c
(0.90 g, 2 mmol) and benzo[d][1,3]dioxole-5-carbaldehyde (0.30 g,
2 mmol), compound 5l (0.58 g, 75%) was also isolated as white
NMR (CDCl3, 600 MHz):
J¼8.4 Hz, 2H, AreH), 6.98e6.95 (m, 2H, AreH), 6.66 (s, 1H, imid-
azole-5-H), 4.03 (s, 2H, CH2); 13C NMR (CDCl3, 100 MHz):
163.5,
d 7.38e7.23 (m, 9H, AreH), 7.08 (d,
d
solid. Mp: 137e139 ꢀC, 1H NMR (CDCl3, 600 MHz):
d
7.38e6.69 (m,
12H, AreH), 6.61 (s, 1H, imidazole-5-H), 5.94 (s, 2H, OCH2), 4.02 (s,
2H, CH2). 13C NMR (CDCl3, 150 MHz):
147.8, 147.4, 145.8, 142.4,
161.8, 145.2, 142.6, 139.5, 136.8, 133.7, 130.4, 129.5, 128.9, 128.4,
126.8, 126.2, 119.5, 115.4, 115.2, 34.9. MS (EI, 70 eV) m/z: 362 (Mþ,
43), 240 (9), 232 (100), 128 (7), 111 (18), 103 (12), 77 (9). Anal. Calcd
for C22H16ClFN2: C, 72.83; H, 4.44; N, 7.72. Found: C, 72.64; H, 4.33;
N, 7.93.
d
139.6, 136.9, 133.5, 129.5, 129.0, 128.4, 126.8, 126.1, 123.9, 122.9,
119.2, 109.0, 108.1, 101.1, 35.0. MS (EI, 70 eV) m/z: 389 (Mþ, 28), 258
(100), 240 (10), 204 (8), 147 (22), 111 (20), 103 (13), 91 (11), 77 (13).
Anal. Calcd for C23H17ClN2O2: C, 71.04; H, 4.41; N, 7.20. Found: C,
71.32; H, 4.29; N, 7.45.
4.4.18. 4-Benzyl-2-(4-chlorophenyl)-1-(2-methylphenyl)-1H-imidaz-
ole (5r). Operation as above with iminophosphorane 3d (0.87 g,
2 mmol) and 4-chlorobenzaldehyde (0.28 g, 2 mmol), compound 5r
(0.54 g, 76%) was also isolated as light yellow solid. Mp:
4.4.13. 4-Benzyl-1-(4-chlorophenyl)-2-(4-nitrophenyl)-1H-imidazole
(5m). Operation as above with iminophosphorane 3c (0.90 g,
2 mmol) and 4-nitrobenzaldehyde (0.30 g, 2 mmol), compound 5m
(0.54 g, 69%) was also isolated as orange solid. Mp: 164e166 ꢀC, 1H
144e146 ꢀC, 1H NMR (CDCl3, 600 MHz):
d
7.37e7.16 (m, 13H, AreH),
6.55 (s, 1H, imidazole-5-H), 4.06 (s, 2H, CH2), 1.91 (s, 3H, CH3). 13
NMR (CDCl3, 150 MHz): 145.0, 142.3, 139.6, 137.5, 134.6, 133.9,
C
d
NMR (CDCl3, 600 MHz):
d
8.12 (d, J¼9.0 Hz, 2H, AreH), 7.55 (d,
131.1, 128.9, 128.8, 128.5, 128.2, 127.2, 126.8, 125.9, 119.9, 34.9, 17.2.
MS (EI, 70 eV) m/z: 358 (Mþ, 62), 240 (9), 228 (100), 193 (12), 103
(15), 91 (44). Anal. Calcd for C23H19ClN2: C, 76.98; H, 5.34; N, 7.81.
Found: C, 77.21; H, 5.15; N, 7.98.
J¼9.0 Hz, 2H, AreH), 7.39e7.23 (m, 7H, AreH), 7.13 (d, J¼9.0 Hz, 2H,
AreH), 6.76 (s, 1H, imidazole-5-H), 4.04 (s, 2H, CH2); 13C NMR
(CDCl3, 150 MHz):
d 147.0, 143.6, 143.5, 139.1, 136.3, 135.9, 134.4,
129.8, 128.8, 128.7, 128.4, 126.9, 126.2, 123.4, 121.2, 34.8. MS (EI,
70 eV) m/z: 389 (Mþ, 49), 342 (8), 259 (100), 240 (10), 204 (10), 128
(9), 111 (18), 103 (17), 91 (9), 77 (11). Anal. Calcd for C22H16ClN3O2:
C, 67.78; H, 4.14; N, 10.78. Found: C, 68.03; H, 4.32; N, 10.65.
4.4.19. 2-(2-Azidophenyl)-4-benzyl-1-(4-chlorophenyl)-1H-imidaz-
ole (5s). Operation as above with iminophosphorane 3c (0.90 g,
2 mmol) and 2-azidobenzaldehyde (0.29 g, 2 mmol) at room tem-
perature for 24 h, compound 5s (0.50 g, 65%) was also isolated as
white solid. Mp: 109e111 ꢀC, IR (KBr, cmꢁ1): 2132, 2103, 1578, 1462,
1399, 1299, 1189, 1095, 1012, 976, 838, 764, 705. 1H NMR (CDCl3,
4.4.14. 4-Benzyl-1-(4-chlorophenyl)-2-phenyl-1H-imidazole
(5n). Operation as above with iminophosphorane 3c (0.90 g,
2 mmol) and benzaldehyde (0.21 g, 2 mmol), compound 5m (0.56 g,
82%) was also isolated as white solid. Mp: 104e106 ꢀC, 1H NMR
600 MHz):
d
7.47e7.00 (m, 13H, AreH), 6.74 (s, 1H, imidazole-5-H),
143.0, 142.8, 139.6,
4.05 (s, 2H, CH2). 13C NMR (CDCl3, 150 MHz):
d
(CDCl3, 600 MHz):
AreH), 6.66 (s, 1H, imidazole-5-H), 4.04 (s, 2H, CH2). 13C NMR
(CDCl3, 150 MHz): 146.1, 142.6, 139.6, 136.9, 133.5, 130.0, 129.4,
129.0, 128.6, 128.4, 128.2, 126.8, 126.1, 119.5, 35.0. MS (EI, 70 eV) m/
z: 344 (Mþ, 43), 340 (9), 214 (100), 111 (18), 103 (16), 91 (6), 77 (12).
Anal. Calcd for C22H17ClN2: C, 76.63; H, 4.97; N, 8.12. Found: C,
76.48; H, 5.19; N, 8.33.
d
7.39e7.22 (m,12H, AreH), 7.09 (d, J¼9.0 Hz, 2H,
138.7, 136.7, 133.1, 132.3, 130.7, 129.2, 129.0, 128.4, 126.2, 125.6,
124.8, 122.5, 118.6, 118.3, 35.0. MS (EI, 70 eV) m/z: 385 (Mþ, 6), 357
(100), 231 (4), 178(9), 129 (11), 111 (14), 91 (28). Anal. Calcd for
C22H16ClN5: C, 68.48; H, 4.18; N, 18.15. Found: C, 68.64; H, 4.36; N,
18.43.
d
4.4.20. 2-(2-Azidophenyl)-4-benzyl-1-phenyl-1H-imidazole
(5t). Operation as above with 2-azidobenzaldehyde (0.29 g,
2 mmol) at room temperature for 24 h, compound 5t (0.42 g, 60%)
was also isolated as light yellow oil. IR (KBr, cmꢁ1): 2127, 2097,
1600, 1497, 1452, 1298, 1027, 756, 694. 1H NMR (CDCl3, 600 MHz):
4.4.15. 4-Benzyl-1-(4-chlorophenyl)-2-(4-methoxyphenyl)-1H-imid-
azole (5o). Operation as above with iminophosphorane 3c (0.90 g,
2 mmol) and 4-methoxybenzaldehyde (0.27 g, 2 mmol), compound
5o (0.60 g, 81%) was also isolated as white solid. Mp: 85e87 ꢀC. 1H
d
7.47e7.02 (m, 14H, AreH), 6.78 (s, 1H, imidazole-5-H), 4.07 (s, 2H,
NMR (CDCl3, 600 MHz):
d
7.38e7.23 (m, 9H, AreH), 7.09 (d,
CH2). 13C NMR (CDCl3, 150 MHz):
d
143.1, 142.6, 139.8, 138.8, 138.2,
J¼7.2 Hz, 2H, AreH), 6.80 (d, J¼6.6 Hz, 2H, AreH), 6.61 (s, 1H, im-
132.4, 130.4, 129.1, 129.0, 128.4, 127.4, 126.1, 124.7, 124.4, 123.0,
118.6, 118.5, 35.1. MS (EI, 70 eV) m/z: 351 (Mþ, 2), 323 (100), 246 (6),
204 (6), 103 (7), 91 (20), 77 (54). Anal. Calcd for C22H17N5: C, 75.19;
H, 4.88; N, 19.93. Found: C, 75.42; H, 4.72; N, 20.17.
idazole-5-H), 4.03 (s, 2H, CH2), 3.79 (s, 3H, CH3). 13C NMR (CDCl3,
150 MHz): d 159.6,146.1,142.4,139.7,137.1,133.4,130.0,129.4,129.0,
128.3, 126.8, 126.1, 122.5, 119.0, 113.6, 55.1, 35.0. MS (EI, 70 eV) m/z:
374 (Mþ, 59), 244 (100), 187 (7), 111 (13), 103 (10), 91 (10), 77 (10).
Anal. Calcd for C23H19ClN2O: C, 73.69; H, 5.11; N, 7.47. Found: C,
73.87; H, 5.35; N, 7.61.
4.5. Synthesis of iminophosphoranes 7
4.5.1. 2-(4-Benzyl-1-(4-chlorophenyl)-1H-imidazol-2-yl)-N-(triphe-
nylphosphoranylidene)aniline (7a). A solution of triphenylphos-
phine (1.05 g, 4 mmol) in dry methylene dichloride (15 mL) was
added dropwise at room temperature to a well-stirred solution of
imidazole 5s (1.54 g, 4 mmol) in dry methylene dichloride (15 mL).
The reaction mixture was stirred at room temperature for 4 h; then
the solvent was removed under reduced pressure. The crude
product was recrystallized from ethanol/petroleum ether (1:2.5) to
give 7a (2.28 g, 92%) as yellow solid. Mp: 191e193 ꢀC, 1H NMR
4.4.16. 4-Benzyl-2-(4-bromophenyl)-1-(4-chlorophenyl)-1H-imidaz-
ole (5p). Operation as above with iminophosphorane 3c (0.90 g,
2 mmol) and 4-bromobenzaldehyde (0.37 g, 2 mmol), compound
5p (0.70 g, 83%) was also isolated as white solid. Mp: 99e101 ꢀC, 1H
NMR (CDCl3, 600 MHz):
J¼8.4 Hz, 2H, AreH), 6.60 (s, 1H, imidazole-5-H), 4.02 (s, 2H, CH2).
13C NMR (CDCl3, 150 MHz):
144.9, 142.8, 139.4, 136.6, 133.8, 131.4,
d 7.40e7.21 (m, 11H, AreH), 7.08 (d,
d
130.0, 129.6, 128.8, 128.3, 126.8, 126.1, 122.7, 119.9, 119.8, 34.9. MS
(EI, 70 eV) m/z: 424 (Mþ, 47), 294 (100), 240 (13), 128 (13), 111 (40),
(CDCl3, 600 MHz):
d
7.50e6.68 (m, 28H, AreH), 6.19 (d, J¼9.0 Hz,

970
Y.-B. Nie et al. / Tetrahedron 68 (2012) 965e971
1H, AreH), 4.13 (s, 2H, CH2). 13C NMR (CDCl3, 150 MHz):
d
149.7,
181 (25), 104 (15), 91 (20), 77 (36). Anal. Calcd for C30H24N4: C,
81.79; H, 5.49; N, 12.72. Found: C, 81.62; H, 5.64; N, 12.95.
148.1,141.8,140.6,137.7,132.2,131.3,130.9,130.2,129.5,128.9,128.2,
127.2, 126.1, 125.8, 124.6, 120.6, 116.6, 116.4, 116.3, 35.2. Anal. Calcd
for C40H31ClN3P: C, 77.47; H, 5.04; N, 6.78. Found: C, 77.68; H, 5.02;
N, 6.63.
4.6.5. N-(3-Benzyl-1-phenylimidazo[1,2-c]quinazolin-5(1H)-yli-
dene)-3-methylaniline (9e). Operation as above with iminophos-
phorane 7b (0.59 g, 1 mmol) and 3-methylphenylisocyanate (0.13 g,
1 mmol), compound 9e (0.40 g, 90%) was also isolated as red solid.
4.5.2. 2-(4-Benzyl-1-phenyl-1H-imidazol-2-yl)-N-(triphenylphos-
phoranylidene)aniline (7b). Operation as above with 5t (1.40 g,
4 mmol), compound 7b (2.08 g, 89%) was also isolated as yellow
Mp: 232e234 ꢀC, 1H NMR (CDCl3, 600 MHz):
d 7.64e7.17 (m, 15H,
AreH), 6.74 (d, J¼7.2 Hz, 1H, AreH), 6.53 (d, J¼8.4 Hz, 1H, AreH),
solid. Mp: 74e76 ꢀC, 1H NMR (CDCl3, 600 MHz):
d 7.48e6.66 (m,
6.39e6.36 (m, 2H, AreH), 5.07 (s, 2H, CH2), 2.34 (s, 3H, CH3). 13C
29H, AreH), 6.17 (d, J¼7.8 Hz, 1H, AreH), 4.14 (s, 2H, CH2). 13C NMR
NMR (CDCl3, 150 MHz): d 152.2, 146.6, 142.6, 137.7, 136.6, 133.0,
(CDCl3, 150 MHz):
d
150.0, 148.1, 141.5, 140.8, 139.3, 132.4, 131.3,
132.8, 130.9, 130.5, 129.6, 128.8, 128.2, 126.9, 125.1, 124.2, 122.1,
121.5, 120.5, 117.4, 104.9, 35.2, 21.7. MS (EI, 70 eV) m/z: 440 (Mþ,
100), 220 (5), 181 (13), 104 (12), 77 (40). Anal. Calcd for C30H24N4: C,
81.79; H, 5.49; N, 12.72. Found: C, 81.89; H, 5.32; N, 12.61.
131.1, 130.5, 129.2, 129.1, 128.3, 125.8, 125.7, 123.6, 120.7, 116.8, 116.5,
35.3. Anal. Calcd for C40H32N3P: C, 82.03; H, 5.51; N, 7.17. Found: C,
81.74; H, 5.68; N, 7.35.
4.6. Synthesis of imidazo[1,2-c]quinazolines 9
4.6.6. N-(3-Benzyl-1-(4-chlorophenyl)imidazo[1,2-c]quinazolin-
5(1H)-ylidene)-3-methylaniline (9f). Operation as above with 3-
methylphenylisocyanate (0.13 g, 1 mmol), compound 9f (0.44 g, 92%)
was also isolated as orange solid. Mp: 249e251 ꢀC, 1H NMR (CDCl3,
4.6.1. N-(3-Benzyl-1-(4-chlorophenyl)imidazo[1,2-c]quinazolin-
5(1H)-ylidene)-4-chloroaniline
(9a). 4-Chlorophenylisocyanate
(0.15 g, 1 mmol) was added dropwise to a solution of iminophos-
phorane 7a (0.62 g, 1 mmol) in dry methylene dichloride (10 mL).
The reaction mixture was stirred at room temperature for 0.5e1 h
until a solid precipitated. The solid formed was filtered off and
recrystallized from ethanol/petroleum ether (2:1) to give 9a (0.46 g,
93%) as orange solid. Mp: 267e269 ꢀC. 1H NMR (CDCl3, 600 MHz):
600 MHz):
d
7.49e7.16 (m, 14H, AreH), 6.76 (d, J¼7.2 Hz, 1H, AreH),
6.57 (d, J¼7.8 Hz, 1H, AreH), 6.45e6.42 (m, 1H, AreH), 6.28 (s, 1H,
imidazole-5-H), 5.02 (s, 2H, CH2), 2.34 (s, 3H, CH3). 13C NMR (CDCl3,
150 MHz):
d 149.5, 137.8, 137.6, 137.1, 134.9, 133.3, 133.0, 130.7, 129.5,
128.8, 128.3, 128.1, 126.9, 125.0, 124.3, 122.0, 121.6, 121.4, 120.5, 117.6,
35.2, 21.7. MS (EI, 70 eV) m/z:474(Mþ,100), 249 (23), 211 (17), 207 (38),
198 (18), 180 (16), 116 (17), 106 (34), 96 (12). Anal. Calcd for C30H23ClN4:
C, 75.86; H, 4.88; N, 11.80. Found: C, 76.12; H, 5.07; N, 11.64.
d
7.60e7.58 (m, 4H, AreH), 7.40e7.22 (m,11H, AreH), 6.61e6.48 (m,
2H, AreH), 6.35 (s, 1H, imidazole-5-H), 5.04 (s, 2H, CH2). MS (EI,
70 eV) m/z: 494 (Mþ, 1), 480 (3), 207 (100), 142 (28), 132 (9), 112 (9),
103 (7), 94 (23), 77 (13). Anal. Calcd for C29H20Cl2N4: C, 70.31; H,
4.07; N, 11.31. Found: C, 70.12; H, 4.32; N, 11.53.
4.6.7. N-(3-Benzyl-1-(4-chlorophenyl)imidazo[1,2-c]quinazolin-
5(1H)-ylidene)aniline (9g). Operation as above with phenyl-
isocyanate (0.12 g, 1 mmol), compound 9g (0.39 g, 85%) was also
isolated as orange solid. Mp: 264e265 ꢀC, 1H NMR (CDCl3,
4.6.2. N-(3-Benzyl-1-(4-chlorophenyl)imidazo[1,2-c]quinazolin-
5(1H)-ylidene)-4-methylaniline (9b). Operation as above with 4-
methylphenylisocyanate (0.13 g, 1 mmol), compound 9b (0.40 g,
84%) was also isolated as orange solid. Mp: 256e258 ꢀC, 1H NMR
600 MHz):
d 7.60e7.24 (m, 15H, AreH), 6.95e6.45 (m, 3H, AreH),
6.32 (s, 1H, imidazole-5-H), 5.06 (s, 2H, CH2). MS (EI, 70 eV) m/z:
460 (Mþ, 100), 383 (9), 191 (24), 111 (25), 103 (11), 91 (16), 77 (36).
Anal. Calcd for C29H21ClN4: C, 75.56; H, 4.59; N, 12.15. Found: C,
75.46; H, 4.87; N, 12.43.
(CDCl3, 600 MHz):
AreH), 6.28 (s,1H, imidazole-5-H), 5.01 (s, 2H, CH2),1.78 (s, 3H, CH3).
13C NMR (CDCl3, 150 MHz):
152.1, 146.3, 142.4, 137.5, 137.0, 134.8,
d 7.49e7.11 (m, 15H, AreH), 6.56e6.42 (m, 2H,
d
133.2, 133.0, 130.7, 129.8, 129.5, 128.9, 128.8, 128.3, 126.9, 124.8, 123.3,
122.1, 121.3, 117.5, 104.6, 35.2, 21.0. MS (EI, 70 eV) m/z: 474 (Mþ, 100),
204 (5), 198 (13), 180 (7), 77 (8). Anal. Calcd for C30H23ClN4: C, 75.86;
H, 4.88; N, 11.80. Found: C, 76.08; H, 5.12; N, 12.09.
4.6.8. N-(3-Benzyl-1-(4-chlorophenyl)imidazo[1,2-c]quinazolin-
5(1H)-ylidene)propan-2-amine (9h). Operation as above with 2-
propylisocyanate (0.09 g, 1 mmol), compound 9h (0.39 g, 91%)
was also isolated as orange solid. Mp: 208e210 ꢀC, 1H NMR (CDCl3,
600 MHz):
d
7.54e7.07 (m, 11H, AreH), 6.45 (d, J¼7.8 Hz, 1H, AreH),
4.6.3. N-(3-Benzyl-1-phenylimidazo[1,2-c]quinazolin-5(1H)-yli-
dene)-4-chloroaniline (9c). Operation as above with iminophos-
phorane 7b (0.59 g, 1 mmol) and 4-chlorophenylisocyanate (0.15 g,
1 mmol), compound 9c (0.39 g, 84%) was also isolated as orange
6.28 (s, 1H, imidazole-5-H), 6.25e6.23 (m, 1H, AreH), 4.91 (s, 2H,
CH2), 4.24e4.22 (m, 1H, CH), 1.19 (d, J¼6.0 Hz, 6H, 2CH3). 13C NMR
(CDCl3, 150 MHz):
d 153.5, 147.0, 138.0, 136.9, 135.2, 133.2, 132.6,
130.7, 129.4, 128.7, 128.2, 126.7, 124.2, 122.2, 120.9, 115.5, 103.1, 46.2,
34.6, 24.4. MS (EI, 70 eV) m/z: 426 (Mþ, 47), 411 (100), 384 (14), 370
(49), 368 (89), 343 (17). Anal. Calcd for C26H23ClN4: C, 73.14; H,
5.43; N, 13.12. Found: C, 73.41; H, 5.36; N, 13.35.
solid. Mp: 251e253 ꢀC, 1H NMR (CDCl3, 600 MHz):
d
7.65e7.20 (m,
16H, AreH), 6.56e6.42 (m, 2H, AreH), 6.39 (s, 1H, imidazole-5-H),
5.03 (s, 2H, CH2). 13C NMR (CDCl3, 150 MHz):
151.5, 148.2, 146.5,
d
142.3, 137.6, 136.4, 133.2, 132.6, 130.5, 129.4, 128.8, 128.6, 128.1,
127.8, 126.8, 126.5, 124.8, 124.7, 122.2, 121.8, 118.0, 105.2, 35.1. MS
(EI, 70 eV) m/z: 460 (Mþ, 100), 281 (6), 206 (18), 191 (12), 77 (63).
Anal. Calcd for C29H21ClN4: C, 75.56; H, 4.59; N, 12.15. Found: C,
75.79; H, 4.33; N, 12.05.
4.6.9. N-(3-Benzyl-1-phenylimidazo[1,2-c]quinazolin-5(1H)-yli-
dene)-4-fluoroaniline (9i). Operation as above with iminophosphor-
ane 7b (0.59 g,1 mmol) and 4-fluorophenylisocyanate(0.14g,1mmol),
compound 9i (0.36 g, 81%) was also isolated as orange solid. Mp:
224e226 ꢀC, 1H NMR (CDCl3, 600 MHz):
d
7.64e6.94 (m, 16H, AreH),
6.55e5.55 (m, 3H, AreH), 5.06 (s, 2H, CH2). 13C NMR (CDCl3,150 MHz):
146.5, 142.5,136.5,133.2, 132.7, 131.0, 130.6,129.5,128.8, 126.8, 125.0,
4.6.4. N-(3-Benzyl-1-phenylimidazo[1,2-c]quinazolin-5(1H)-yli-
dene)-4-methylaniline (9d). Operation as above with iminophos-
phorane 7b (0.59 g, 1 mmol) and 4-methylphenylisocyanate (0.13 g,
1 mmol), compound 9d (0.67 g, 83%) was also isolated as orange
d
124.5,122.2,121.7,117.7,114.7,114.5,105.0, 35.2. MS (EI, 70 eV) m/z: 444
(Mþ,100), 368 (7),183 (20), 77 (34). Anal. Calcd for C29H21FN4: C, 78.36;
H, 4.76; N, 12.60. Found: C, 78.27; H, 4.92; N, 12.58.
solid. Mp: 225e227 ꢀC, 1H NMR (CDCl3, 600 MHz):
d
7.63e7.10 (m,
16H, AreH), 6.52e6.36 (m, 3H, AreH), 5.07 (s, 2H, CH2), 2.32 (s, 3H,
CH3). 13C NMR (CDCl3, 150 MHz):
146.5, 137.8, 136.6, 133.0, 132.7,
d
4.6.10. N-(3-Benzyl-1-phenylimidazo[1,2-c]quinazolin-5(1H)-yli-
dene)aniline (9j). Operation as above with iminophosphorane 7b
(0.59 g, 1 mmol) and phenylisocyanato (0.12 g, 1 mmol), compound
130.9, 130.5, 129.6, 128.9, 128.8, 126.9, 125.1, 123.4, 122.1, 121.7,
121.5, 117.3, 35.1, 21.0. MS (EI, 70 eV) m/z: 440 (Mþ, 100), 222 (13),

Y.-B. Nie et al. / Tetrahedron 68 (2012) 965e971
971
9j (0.35 g, 82%) was also isolated as orange solid. Mp: 262e264 ꢀC,
1H NMR (CDCl3, 600 MHz):
7.69e7.25 (m, 16H, AreH), 6.94e6.41
(m, 3H, AreH), 6.37 (s, 1H, imidazole-5-H), 5.08 (s, 2H, CH2). MS (EI,
70 eV) m/z: 426 (Mþ, 100), 349 (16), 282 (9), 206 (16), 174 (17), 104
(10), 77 (60). Anal. Calcd for C29H22N4: C, 81.66; H, 5.20; N, 13.14.
Found: C, 81.85; H, 5.42; N, 13.07.
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We gratefully acknowledge financial support of this work by the
National Natural Science Foundation of China (Nos. 21032001,
21172085) and the self-determined research funds of CCNU from
the colleges’ basic research and operation of MOE (No. 10020176).
Supplementary data
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Supplementary data related to this article can be found online at
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