An efficient synthesis of quinazoline derivatives with the aid of low-valent titanium reagent

Article abstract of DOI:10.1002/jhet.5570420201

Quinazolin-4(3H)-ones, 1,2-dihydroquinazolin-4(3H)-ones, 3,4-dihydroquinazolines, imidazo[1,2-c]-quinazolines and 5,6-dihydroimidazo[1,2- c]quinazolines were synthesized by the novel reductive reaction of nitro group, N-H bond and ortho-ester, aldehydes o

Full text of DOI:10.1002/jhet.5570420201

March 2005
173
An Efficient Synthesis of Quinazoline Derivatives With the Aid of
Low-valent Titanium Reagent
Daqing Shi,* Chunling Shi, Juxian Wang, Liangce Rong,
Qiya Zhuang, and Xiangshan Wang
Department of Chemistry, Xuzhou Normal University, Key Laboratory of Biotechnology on Medical Plant of
Jiangsu Province, Xuzhou, Jiangsu 221116, P. R. China
Fax: 86-516-3403164.
E-mail: dqshi@263.net.
Received February 13, 2004
Quinazolin-4(3H)-ones, 1,2-dihydroquinazolin-4(3H)-ones, 3,4-dihydroquinazolines, imidazo[1,2-c]-
quinazolines and 5,6-dihydroimidazo[1,2-c]quinazolines were synthesized by the novel reductive reaction of
nitro group, N-H bond and ortho-ester, aldehydes or ketones promoted by the low-valent titanium reagent
(TiCl -Zn system). The structures of these compounds were characterized by elemental analysis, IR and
4
1
HNMR spectra and further confirmed by single crystal X-ray diffraction analysis.
J. Heterocyclic Chem., 42, 173 (2005).
The pyrimidine ring constitutes a basic heteroaromatic
structure. It is a vital building block for the construction of
other heterocyclic ring compounds and alkloids. A large
number of compounds containing the pyrimidine ring pos-
sess a wide range of pharmacological activities. Quinazolin-
4(3H)-one derivatives (I) have been reported to exhibit anti-
convulsant [1], antihypertensive [2], antidiabetic [3],
antibacterial [4], antitumor [5], antihistaminic [6] and anti-
inflammatory [7] activities. Some polyheterocyclic struc-
tures such as indole[1,2-c]quinazoline (II) and benzimi-
dazo[1,2-c]quinazoline (III) skeletons have been reported to
represent potent cytotoxic agents [8] (Figure 1). Therefore,
the development of novel and convenient synthetic methods
for the preparation of quinazolin-4(3H)-ones and quinazo-
lines still remains an active research area.
[15] and 2-arylquinolines [16] with the aid of low-valent
titanium reagent. We have reported the primary results for
the synthesis of the quinazolin-4(3H)-ones and 1,2-dihy-
droquinazolin- 4(3H)-ones with the aid of a low-valent
titanium reagent [17]. Here, we wish to describe in detail
the methods induced by the TiCl -Zn system for the prepa-
4
ration of quinazolin-4(3H)-ones, quinazolines and imi-
dazo[1,2-c]quinazolines.
When N-substituted-o-nitrobenzamides 1 and triethyl
orthoformate 2 were treated with low-valent titanium pre-
pared from titanium tetrachloride and zinc powder in
anhydrous THF, the intermolecular reductive cross-cou-
pling products 3-substituted quinazolin- 4(3H)-ones 3
were obtained (Scheme 1).
Scheme 1
Figure 1
Low-valent titanium reagents have an exceeding high
ability to promote reductive coupling of carbonyl com-
pounds and are attracting increasing interest in organic
synthesis [9]. Many other functional groups can be reacted
[10]. Recently, we have reported the low-valent titanium-
induced intermolecular reductive coupling reaction of car-
boxylic derivatives with aromatic ketones [11], the
intramolecular reductive coupling reaction of 4,4-dicyano-
1,3-diaryl-1- butanone [12] and the cyclodimerization of
α,β-unsaturated ketones [13]. In the course of our work on
the application of low-valent titanium reagents in the
preparation of bioactive heterocyclic compounds, we have
reported the synthesis of indoles [14], 2-aminoquinolines
Table 1 summarized our results on the reaction of N-sub-
stituted-o-nitrobenzamides and triethyl orthoformate with
low-valent titanium reagent. The chloro and bromo groups
of the substrates could not be reduced under the reaction
conditions and no influence on the rate of reductive cou-
pling reaction was observed. On treating triethyl orthofor-
mate with N-phenyl-o-aminobenzamide under the same
reaction conditions, no reaction took place and no
3-phenylquinazolin-4(3H)-one could be detected.
Treatment of o-nitrobenzyl amines 4 and triethyl ortho-
formate 2 with TiCl /Zn in anhydrous THF under the same
4
reaction conditions afforded 3,4-dihydroquinazolines 5 in
good yields (Scheme 2). Table 2 summarized our results.

174
D. Shi, C. Shi, J. Wang, L. Rong, Q. Zhuang, and X. Wang
Vol. 42
Table 3
Table 1
Synthesis of IImidazo[1,2-c]quinazolines Induced by Low-valent
Synthesis of 3-Substituted Quinazolin-4(3H)-ones Induced
Titanium Reagent
by Low-valent Titanium Reagent
1
2
Entry
Ar
X
Y
R
Yield (%)
Entry
R
R
Yield(%)
8a
8b
8c
8d
8e
8f
8g
8h
8i
C H
H
Cl
CH O
H
CH O
Cl
H
Cl
H
Cl
H
H
CH O
H
CH O
H
H
H
H
H
H
H
H
CH
CH
CH
H
H
H
68
74
62
70
61
65
68
72
63
69
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
Cl
Cl
Cl
H
Cl
H
C H
4-CH C H
C H CH
6 5
84
84
71
79
72
46
73
81
72
86
6
5
5
5
5
5
5
6
5
C H
6
3 6 4
C H
6
3
3
2
2
C H
C H CH
6
3
3
3
6 5
C H
4-ClC H CH
6
3
3
6
4
2
C H
C H -c
6
6
11
4-CH C H
4-CH C H
4-BrC H
4-BrC H
4-IC H
4-IC H
2-ClC H
2-ClC H
3 6
4
4
6
4
3
6
6
4
6
4
4
6
4
4
8j
H
3j
Cl
6
6
Table 2
Synthesis of 3,4-Dihydroquinazolines Promoted by Low-valent
Titanium Reagent
quinazolin-4(3H)-ones 10 in good yields (Scheme 4).
Table 4 summarized our results. All reactions could be car-
ried out under mild conditions. However, N-phenyl-o-
nitrobenzamide failed to react with butanone, 3-pentanone,
cyclopentanone, cyclohexanone, benzaldehyde or ace-
tophenone under these conditions, although the reaction of
o-nitrobenzamide 1 and the cyclic ketone 11 with the same
reagent system afford 2,2-polymethylene-1,2-dihydro-
quinazolin-4(3H)-ones 12 (Scheme 5) and the results are
summarized in Table 5. However, o-nitrobenzamide failed
to react with acetophenone or 1-tetralone.
Entry
R
Ar
Yield(%)
5a
5b
5c
5d
5e
5f
H
H
Cl
Cl
Cl
Cl
4-ClC H
73
84
71
83
79
82
6
4
4-BrC H
6
4
C H
6 5
4-CH C H
6 4
3
4-ClC H
6
4
4-BrC H
6
4
Similarly, 2-(o-nitrophenyl)imidazole 6 and ortho-ester
7 were treated with low-valent titanium reagent in anhy-
drous THF under the same reaction conditions. The
desired products imidazo[1,2- c]quinazolines 8 were
obtained in moderate yields (Scheme 3). The results are
summarized in Table 3.
Scheme 4
Scheme 2
Scheme 5
Moroever, treatment of o-nitrobenzamides 1 and ketones
or aromatic aldehydes 9 with TiCl /Zn in anhydrous THF
4
under the same reaction conditions afforded 1,2-dihydro-
Scheme 3
However, treatment of 2-(o-nitrophenyl)imidazolines 6
and ketones or aromatic aldehydes 9 with TiCl /Zn system
4
in dry THF under the same reaction conditions gave the
desired cross-coupling products 5,6-dihydroimidazo[1,2-
c]quinazolines 13 were obtained in moderated yields
(Scheme 6).

March 2005
Synthesis of Quinazoline Derivatives With the Aid of Low-valent Titanium Reagent
175
Table 4
Table 6
Synthesis of 1,2-Dihydroquinazolin-4(3H)-ones Promoted by Low-
1
2
valent Titanium Reagent
Entry
Ar
4-BrC H
X
Y
R
R
Yield (%)
1
2
3
4
Entry
R
R
R
R
Yield (%)
13f
13g
H
Cl
H
Cl
H
H
H
Cl
Cl
H
H
H
H
H
H
H
H
H
CH
CH
CH
CH
CH
H
CH
CH
CH
CH
CH
80
83
69
73
75
76
81
6
4
4
3
3
3
3
3
3
3
3
3
3
4-BrC H
6
10a
10b
10c
10d
10e
10f
10g
10h
10i
10j
10k
10l
10m
10n
10o
10p
10q
H
H
H
Cl
Cl
Cl
H
Cl
H
H
H
Cl
Cl
H
H
Cl
Cl
4-CH C H
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
88
71
83
85
89
87
72
73
71
79
86
74
71
91
93
80
87
3
6
4
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
13h 4-CH OC H
13i 4-CH OC H
13j
13k
13l
3
6
4
4
4-ClC H
6 4
3
6
4-BrC H
6 4
4-FC H
6 4
C H
6 5
C H
4-CH C H
3 6 4
3,4-(CH O) C H
3 2 6 3
4-CH C H
3 6 4
4-CH OC H
3 6 4
4-CH C H
6
5
5
5
5
3
6
4
C H
H
H
H
4-BrC H
6
6
4
CH (CH )
13m
13n
C H
79
70
3
2 7
6
CH (CH )
C H
3
2 7
6
C H CH
6
5
2
H
C H
2
5
5
5
5
All the products 3, 5, 8, 10, 12 and 13 were characterized
by IR, HNMR and elemental analysis. The structures of
H
H
H
H
H
H
H
C H
C H
2
2
5
1
CH
C H
3
2
C H
C H
8f, 10a, 12b and 13c were further confirmed by single
crystal X-ray diffraction analysis. Fig.2 to Fig.5 show the
molecular structures of 8f, 10a, 12b and 13c, respectively.
The crystallographic data of these compounds are summa-
rized in Table 7
2
5
2
H
H
H
H
4-CH C H
3,4-OCH OC H
2 6 3
4-CH C H
4-CH OC H
6 4
3 6 4
3 6 4
3
Table 5
Synthesis of 2,2-Polymethylene-1,2-dihydroquinazolin-
4(3H)-ones Induced by Low-valent Titanium Reagent
Entry
R
n
Yield (%)
12a
12b
12c
12d
H
H
Cl
Cl
1
2
1
2
84
63
89
83
Scheme 6
Figure 2 X-ray structure of 8f.
Table 6 summarizes our results. All reactions could be
carried out under mild conditions. However, 2-(o-nitro-
phenyl)imidazoles failed to react with butanone, 3-pen-
tanone, cyclohexanone or acetophenone under these
conditions.
Table 6
Synthesis of 5,6-Dihydroimidazo[1,2-c]quioazolines Promoted by Low-
valent Titanium Reagent
1
2
Entry
Ar
C H
X
Y
R
R
Yield (%)
13a
13b
13c
13d
13e
H
Cl
OCH
H
H
H
O
H
H
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
71
74
62
82
84
6
5
5
5
3
3
3
3
3
3
3
3
3
3
C H
6
C H
6
2
4-CH C H
3
6
4
4
4-CH C H
Cl
Figure 3 X-ray structure of 10a.
3
6

176
D. Shi, C. Shi, J. Wang, L. Rong, Q. Zhuang, and X. Wang
Vol. 42
Table 7
Crystallographic Data for 8f, 10a, 12b and 13c
8f
10a
12b
13c
Empirical formula
Formula weight
Temperature (K)
Wave length (Å)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
α (˚)
C
H
ClN
C
H
N O
C
H
N O
C H N O
25 21 3 2
395.45
296(2)
0.71073
Monoclinic
23 16
3
17 18
2
13 16
2
369.84
291(2)
0.71073
Monoclinic
P2 /c
7.789(1)
17.777(2)
26.040(3)
90
266.33
295(2)
0.71073
Monoclinic
P2 /n
11.917(2)
6.911(1)
17.821(4)
90
216.28
296(2)
0.71073
Monoclinic
P2 /n
10.387(1)
10.954(2)
10.827(2)
90
P2 /c
1
1
1
1
9.594(2)
16.928(4)
12.865(3)
90
β (˚)
γ (˚)
V (Å )
Z
94.70(1)
90
3593.7(9)
8
1.367
0.225
98.81(1)
90
1450.4(5)
4
1.220
0.077
110.77(1)
90
1151.8(4)
4
1.247
0.080
95.73(2)
90
2079.1(8)
4
1.263
0.082
832
3
3
Dcalc. (Mg/m )
Absorption coefficient(mm )
F(000)
-1
1536
568
464
Crystal size (mm)
θ Range (˚)
Limiting indices
0.54x0.48x0.34
1.39 to 25.00
0≤h≤9
0≤k≤21
-30≤l≤30
7325
0.56x0.52x0.32
1.93 to 25.50
0≤h≤14
0≤k≤8
-21≤l≤21
3202
0.52x0.48x0.44
2.34 to 25.00
0≤h≤12
0≤k≤13
-12≤l≤12
2681
0.48x0.38x0.26
1.99 to 25.50
0≤h≤11
0≤k≤20
-15≤l≤15
4424
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F
6330
6330/0/490
0.795
2706
2706/0/189
0.921
2033
2033/0/146
1.087
3873
3873/0/278
0.817
2
Final R indices [I>2σ(I)]
R indices (all data )
R =0.0391
wR=0.0747
R =0.0433
wR=0.1076
R =0.0449
wR=0.1217
R =0.0482
wR=0.1134
1
1
1
1
R =0.0983
R =0.0770
R =0.0572
R =0.1065
1
1
1
1
w R=0.0868
0.0035(2)
0.136 and –0.225
w R=0.1194
0.0114(16)
0.136 and –0.136
w R=0.1276
0.068(6)
0.296 and –0.310
wR=0.1274
0.0096(12)
0.281 and –0.204
Extinction coefficient
Largest diff. Peak and hole (e•Å )
-3
Figure 4. X-ray structure of 12b.
In conclusion, a series of quinazolin-4(3H)-ones, 1,2-
dihydroquinazolin-4(3H)-ones, 3,4-dihydroquinazolines,
imidazo[1,2-c]quinazolines and 5,6-dihydroimidazo[1,2-
c]quinazolines were synthesized via novel reductive reac-
tion of nitro group, N-H bond and ortho-ester or carbonyl
Figure 5. X-ray structure of 13c.
EXPERIMENTAL
group induced by the TiCl /Zn system. The advantages of
our methods are the easily accessible starting materials,
convenient manipulation and moderate to high yields.
4
Melting point were determined in open capillaries and are uncor-
rected. IR spectra were recorded on a FTIR-8101 spectrometer.
HNMR spectra were measured on an Inova-400 MHz spectrometer
1

March 2005
Synthesis of Quinazoline Derivatives With the Aid of Low-valent Titanium Reagent
177
using TMS as internal standard, CDCl as solvent. Microanalysis
8.10 (s, 1H, H2), 7.70 (s, 1H, H8), 7.46 (d, J= 8.4 Hz, 1H, H6),
3
were carried out on Perkin-Elmer 2400 II instruments. X-ray diffrac-
tion was recorded on a Siemens P4 diffractometer.
7.34-7.21 (m, 4H), 5.14 (s, 2H, CH ); IR (KBr): 3050, 2946,
2
1672, 1626, 1602, 1530, 1456, 1409, 1350, 1317, 1303, 1232,
-1
1106, 1089, 1015, 910, 841, 798 cm .
General Procedure for the Synthesis of Quinazolin-4(3H)-ones.
Anal. Calcd. for C H Cl N O: C, 59.04; H, 3.30; N, 9.18.
15 10
2 2
TiCl (2.2 mL, 20 mmol) was added dropwise using a syringe to
Found: C, 58.89; H, 3.53; N, 8.96.
4
a stirred suspension of zinc dust (2.6 g, 40 mmol) in freshly dis-
tilled anhydrous THF (20 mL) at room temperature under a dry
nitrogen atmosphere. After completion of the addition, the mixture
was refluxed for 2 h. The suspension of the low-valent titanium
reagent formed was cooled to room temperature and a solution of
N-aryl-o-nitrobenzamide (5 mmol) and triethyl orthoformate (10
mmol) in THF was added dropwise. The mixture was refluxed for
7-Chloro-3-cyclohexylquinazolin-4(3H)-one (3f).
This compound was obtained as solid with mp 120-121 ºC;
1
HNMR (400 MHz, CDCl ): δ = 8.24 (d, J = 8.8 Hz, 1H, H5),
3
8.13 (s, 1H, H2), 7.70 (s, 1H, H8), 7.44 (d, J= 8.8 Hz, 1H, H6),
4.79 (m, 1H, NCH), 2.02-1.94 (m, 6H, 3xCH ), 1.65-1.51 (m, 4H,
2
2xCH ); IR (KBr): 2933, 2854, 1678, 1600, 1461, 1402, 1352,
2
-1
5 h under N (the reaction was monitored by TLC). The reaction
1318, 1270, 1162, 1130, 1068, 910, 891, 872, 827, 778 cm .
2
mixture was quenched with 10% HCl (50 mL) and extracted with
Anal. Calcd. for C H ClN O: C, 64.00; H, 5.75; N, 10.66.
14 15
2
CHCl (3x50 mL). The combined extracts were washed with water
Found: C, 64.25; H, 5.63; N, 10.58.
3
(3x50 mL) and dried over anhydrous Na SO After evaporation of
the solvent under reduced pressure, the crude products 3a-j were
2
4.
3-(4'-Iodophenyl)quinazolin-4(3H)-one (3g).
This compound was obtained as solid with mp 194-195 ºC;
purified by recrystallization from 95% ethanol.
1
HNMR (400 MHz, CDCl ): δ = 8.36 (d, J = 7.2 Hz, 1H, H5),
3
3-Phenylquinazolin-4(3H)-one (3a).
8.09 (s, 1H, H2), 7.89 (d, J = 8.4 Hz, 2H), 7.84-7.77 (m, 2H),
7.59-7.55 (m, 1H), 7.18 (d, J = 8.4 Hz, 2H);IR (KBr): 3041,
1674, 1607, 1487, 1469, 1397, 1322, 1295, 1185, 1109, 1006,
This compound was obtained as solid with mp 140-142 ºC
1
(Lit.18 138-140 ºC); HNMR (400 MHz, CDCl ): δ = 8.38 (d, J =
3
-1
8.4 Hz, 1H, H5), 8.15 (s, 1H, H2), 7.81 (dd, J = 8.4 Hz, J = 7.6
911, 849, 812, 769, 690 cm .
1
2
Hz, 1H, H7), 7.78 (d, J = 8.4 Hz, 1H, H8), 7.57 (dd, J = 8.4 Hz,
Anal. Calcd. for C H IN O: C, 48.30; H, 2.61; N, 8.05.
1
14
9
2
J = 7.6 Hz, 1H, H6), 7.54-7.51 (m, 3H), 7.46-7.43 (m, 2H); IR
Found: C, 48.47; H, 2.76; N, 7.81.
2
(KBr): 3030, 1672, 1610, 1473, 1402, 1262, 1181, 1111, 1024,
933, 913, 767, 699 cm .
7-Chloro-3-(4'-iodophenyl)quinazolin-4(3H)-one (3h).
-1
This compound was obtained as solid with mp 239-240 ºC;
3-(4'-Methylphenyl)quinazolin-4(3H)-one (3b).
1
HNMR (400 MHz, CDCl ): δ = 8.30 (d, J = 8.4 Hz, 1H, H5),
3
This compound was obtained as solid with mp 147-149 ºC
8.11 (s, 1H, H2), 7.92 (d, J = 8.4 Hz, 2H), 7.79 (s, 1H, H8), 7.55
(d, J = 8.4 Hz, 1H, H6), 7.20 (d, J = 8.4 Hz, 2H); IR (KBr): 3049,
1688, 1605, 1483, 1464, 1428, 1396, 1307, 1294, 1085, 1059,
1
(Lit.18 148-149 ºC); HNMR (400 MHz, CDCl ): δ = 8.38 ( d, J
3
= 8.4 Hz, 1H, H5), 8.13 (s, 1H, H2), 7.81 (dd, J = 8.4 Hz, J =
1
2
-1
8.4 Hz, 1H, H7), 7.77 (d, J = 8.4 Hz, H8), 7.55 (dd, J = 8.4 Hz,
1008, 915, 895, 835, 815, 784, 693 cm .
1
J = 8.4 Hz, 1H, H6), 7.36 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz,
Anal. Calcd. for C H ClIN O: C, 43.95; H, 2.11; N, 7.32.
2
14
8
2
2H), 2.44 (s, 3H, CH ); IR (KBr): 3030, 1689, 1600, 1514, 1471,
1323, 1293, 1192, 1114, 1025, 917, 836, 817, 770, 749, 694 cm .
Found: C, 44.19; H, 1.93; N, 7.58.
3
-1
3-(2'-Chlorophenyl)quinazolin-4(3H)-one (3i).
3-Benzylquinazolin-4(3H)-one (3c).
This compound was obtained as solid with mp 221-222 ºC;
1
This compound was obtained as solid with mp 114-115 ºC;
HNMR (400 MHz, CDCl ): δ = 8.38 (d, J = 8.0 Hz, 1H, H5),
3
1
HNMR (400 MHz, CDCl ): δ = 8.36 (d, J = 7.6 Hz, 1H, H5),
7.98 (s, 1H, H2), 7.86-7.79 (m, 2H), 7.64-7.43 (m, 5H); IR
(KBr): 3062, 1681, 1605, 1470, 1394, 1373, 1301, 1266, 1186,
3
8.15 (s, 1H, H2), 7.80-7.72 (m, 2H), 7.54 (dd, J = 7.2 Hz, J =
7.6 Hz, 1H), 7.37-7.29 (m, 5H), 5.21 (s, 2H, CH ); IR (KBr):
1
2
-1
1114, 1083, 1021, 917, 867, 776, 755, 726, 696 cm .
2
3036, 2945, 1677, 1604, 1473, 1440, 1411, 1365, 1320, 1289,
1161, 1149, 1076, 937, 869, 776, 706, 692 cm .
Anal. Calcd. for C H ClN O: C, 65.51; H, 3.53; N, 10.91.
Found: C, 65.72; H, 3.28; N, 11.15.
14
9
2
-1
Anal. Calcd. for C H N O: C, 76.25; H, 5.12; N, 11.86.
Found: C, 76.42; H, 4.93; N, 11.90.
15 12
2
7-Chloro-3-(2'-chlorophenyl)quinazolin-4(3H)-one (3j).
This compound was obtained as solid with mp 188-189 ºC;
7-Chloro-3-benzylquinazolin-4(3H)-one (3d).
1
HNMR (400 MHz, CDCl ): δ = 8.30 (d, J = 8.8 Hz, 1H, H5),
3
This compound was obtained as solid with mp 119-120 ºC;
7.99 (s, 1H, H2), 7.81 (s, 1H, H8), 7.63 (d, J = 8.8 Hz, 1H, H6),
7.55-7.45 (m, 4H); IR (KBr): 3032, 1682, 1646, 1604, 1528,
1466, 1440, 1390, 1302, 1266, 1087, 900, 836, 761, 692 cm .
1
HNMR (400 MHz, CDCl ): δ = 8.25 (d, J = 8.8 Hz, 1H, H5),
3
-1
8.13 (s, 1H, H2), 7.77 (s, 1H, H8), 7.47 (d, J= 8.8 Hz, 1H, H6),
7.39-7.31 (m, 5H), 5.19 (s, 2H, CH ); IR (KBr): 2947, 1690,
Anal. Calcd. for C H Cl N O: C, 57.76; H, 2.77; N, 9.62.
2
14
8
2 2
1601, 1554, 1456, 1400, 1365, 1316, 1216, 1167, 1110, 1070,
946, 894, 876, 819, 781, 756, 715, 699 cm .
Found: C, 57.94; H, 2.47; N, 9.76.
-1
General Procedure for the Synthesis of 3,4-Dihydroquinazolines.
Anal. Calcd. for C H ClN O: C, 66.55; H, 4.10; N, 10.35.
15 11
2
A solution of o-nitrobenzyl amine 4 (5 mmol) and triethyl
orthoformate (10 mmol) in anhydrous THF (10 mL) was added
carefully at room temperature to a suspension of low-valent tita-
nium reagent (20 mmol) prepared as mentioned above. When
Found: C, 66.78; H, 3.86; N, 10.51.
7-Chloro-3-(4'-chlorobenzyl)quinazolin-4(3H)-one (3e).
This compound was obtained as solid with mp 139-140 ºC;
1
HNMR (400 MHz, CDCl ): δ = 8.23 (d, J = 8.4 Hz, 1H, H5),
the reaction was completed (at refluxing under N ), most of the
3
2

178
D. Shi, C. Shi, J. Wang, L. Rong, Q. Zhuang, and X. Wang
Vol. 42
solvent was removed in vacuo. The residue was poured into 10%
IR (KBr): 3060, 1600, 1560, 1550, 1490, 1280, 1230, 1170,
1090, 925, 820 cm .
-1
HCl (100 mL), and extracted with CHCl (3x50 mL). The com-
3
bined organic layers were washed with water (3x50 mL), dried
Anal. Calcd. for C H B ClN : C, 52.29; H, 3.13; N, 8.71.
14 10
r
2
(Na SO ), and the solvent was removed in vacuo to give the
Found: C, 52.53; H, 2.94; N, 8.97.
2
4
crude product. The crude product was recrystallized from
ethanol to give the pure product.
General Procedure for the Synthesis of Imidazo[1,2-c]quinazo-
lines.
3-(4'-Chlorophenyl)-3,4-dihydroquinazoline (5a).
A solution of 2-(o-nitrophenyl)imidazole 6 (2 mmol) and
ortho-ester 7 (4 mmol) in anhydrous THF (10 mL) was added
carefully at room temperature to a suspension of low-valent tita-
nium reagent (10 mmol) prepared as mentioned above. When the
This compound was obtained as solid with mp 140-141 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.56 (s, 1H, H2), 7.40 (d, J =
3
8.8 Hz, 2H), 7.29-7.21(m, 2H, H6, H7), 7.15 (d, J = 7.6 Hz, 1H,
H8), 7.10 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 6.4 Hz, 1H, H5), 4.92
(s, 2H, H4); IR (KBr): 3067, 2810, 1600, 1565, 1550, 1470,
reaction was completed (at room temperature under N ), most of
2
the solvent was removed in vacuo. The residue was poured into
-1
1290, 1230, 1160, 920, 800, 735 cm .
10% HCl (50 mL), and extracted with CHCl (3x50 mL). The
3
Anal. Calcd. for C H ClN : C, 69.29; H, 4.57; N, 11.54.
combined organic layers were washed with water (3x50 mL),
14 11
2
Found: C, 69.53; H, 4.26; N, 11.72.
dried (Na SO ), and the solvent was removed in vacuo to give
2
4
the crude product. The crude product was purified by column
chromatography on silica gel (200-300 mesh) using petroleum
ether (b. p. 60-90 ºC) – acetone (5:1) as eluent.
3-(4'-Bromophenyl)-3,4-dihydroquinazoline (5b).
This compound was obtained as solid with mp 144-145 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.58 (s, 1H, H2), 7.55 (d, J =
3
2,3-Diphenylimidazo[1,2-c]quinazoline (8a).
8.8 Hz, 2H), 7.27-7.13 (m, 3H, H6, H7, H8), 7.05 (d, J = 8.8 Hz,
2H), 7.01 (d, J = 7.2 Hz, 1H, H5), 4.92 (s, 2H, H4); IR (KBr):
3055, 1610, 1560, 1550, 1490, 1370, 1300, 1235, 1165, 1080,
This compound was obtained as solid with mp 193-195 ºC;
1
HNMR (400 MHz, CDCl ): δ = 8.72 (s, 1H), 7.97 (d, J = 7.6 Hz,
3
-1
1000, 920, 800, 750 cm .
1H), 7.86 (d, J = 8.0 Hz, 1H), 7.74-7.70 (m, 4H), 7.59-7.50 (m,
Anal. Calcd. for C H BrN : C, 58.56; H, 3.86; N, 9.76.
Found: C, 58.75; H, 3.68; N, 9.54.
5H), 7.41-7.30 (m, 3H); IR (KBr): 3058, 1603, 1473, 1379, 1353,
1310, 1262, 1235, 894, 778, 746, 704, 693 cm .
14 11
2
-1
Anal. Calcd. for C
Found: C, 82.41; H, 4.46; N, 13.16.
H N : C, 82.22; H, 4.70; N, 13.08.
22 15 3
6-Chloro-3-phenyl-3,4-dihydroquinazoline (5c).
This compound was obtained as solid with mp 126-127 ºC;
9-Chloro-2,3-diphenylimidazo[1,2-c]quinazoline (8b).
1
HNMR (400 MHz, CDCl ): δ = 7.59 (s, 1H, H2), 7.47-7.43 (m,
3
2H), 7.24-7.14 (m, 5H), 6.99 (s, 1H, H5), 4.93 (s, 2H, H4); IR
(KBr): 3060, 1593, 1580, 1550, 1500, 1367, 1283, 1217, 810,
740 cm .
This compound was obtained as solid with mp 216-217 ºC;
1
HNMR (400 MHz, CDCl ): δ = 8.75 (s, 1H), 8.49 (s, 1H), 7.98
3
-1
(d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.67-7.61 (m, 7H),
Anal. Calcd. for C H ClN : C, 69.29; H, 4.57; N, 11.54.
Found: C, 69.45; H, 4.38; N, 11.39.
7.38-7.31 (m, 3H); IR (KBr): 3049, 1601, 1468, 1404, 1352,
1309, 1082, 1024, 901, 831, 781, 750, 700, 683 cm .
14 11
2
-1
Anal. Calcd. for C H ClN : C, 74.26; H, 3.97; N, 11.81.
Found: C, 74.42; H, 3.75; N, 11.69.
22 14
3
6-Chloro-3-(4'-methylphenyl)-3,4-dihydroquinazoline (5d).
This compound was obtained as solid with mp 181-182 ºC;
8,9-Dimethoxy-2,3-diphenylimidazo[1,2-c]quinazoline (8c).
1
HNMR (400 MHz, CDCl ): δ = 7.55 (s, 1H, H2), 7.24 (d, J =
3
8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 1H, H7), 7.13 (d, J = 8.0 Hz, 1H,
H8), 7.06 (d, J = 8.0 Hz, 2H), 6.98 (s, 1H, H5 ), 4.91 (s, 2H, H4),
This compound was obtained as solid with mp 206-207 ºC;
1
HNMR (400 MHz, CDCl ): δ = 8.63 (s, 1H), 7.82 (s, 1H), 7.68-
3
2.37 (s, 3H, CH ); IR (KBr): 3045, 1593, 1550, 1490, 1380,
1283, 1250, 1207, 907, 817, 800 cm .
7.56 (m, 7H), 7.43 (s, 1H), 7.36-7.29 (m, 3H), 4.02 (s, 3H,
3
-1
CH O), 3.94 (s, 3H, CH O); IR (KBr): 3049, 2933, 1622, 1495,
3
3
Anal. Calcd. for C H ClN : C, 70.18; H, 5.10; N, 10.91.
Found: C, 70.41; H, 4.86; N, 11.07.
1462, 1383, 1340, 1271, 1217, 1134, 1030, 984, 883, 860, 818,
787, 744, 704 cm .
15 13
2
-1
Anal. Calcd. for C H N O : C, 75.57; H, 5.02; N, 11.02.
Found: C, 75.71; H, 4.86; N, 11.23.
24 19
3 2
6-Chloro-3-(4'-chlorophenyl)-3,4-dihydroquinazoline (5e).
This compound was obtained as solid with mp 187-188 ºC;
5-Methyl-2,3-diphenylimidazo[1,2-c]quinazoline (8d).
1
HNMR (400 MHz, CDCl ): δ = 7.53 (s, 1H, H2), 7.41 (d, J =
3
8.8 Hz, 2H), 7.22 (d, J = 8.8 Hz, 1H, H7), 7.14 (d, J = 8.8 Hz, 1H,
H8), 7.10 (d, J = 8.8 Hz, 2H), 7.00 (s, 1H, H5), 4.88 (s, 2H, H4);
IR (KBr): 3060, 1600, 1565, 1550, 1480, 1380, 1280, 1230,
This compound was obtained as solid with mp 188-189 ºC;
1
HNMR (400 MHz, CDCl ): δ = 8.02-7.84 (m, 4H), 7.70-7.50
3
(m, 7H), 7.40-7.36 (m, 3H), 2.66 (s, 3H, CH ); IR (KBr): 3050,
3
-1
1160, 1100, 930, 870, 810 cm .
1697, 1623, 1575, 1537, 1358, 1333, 1280, 1242, 1174, 823, 766,
-1
Anal. Calcd. for C H Cl N : C, 60.67; H, 3.64; N, 10.11.
743, 703 cm .
14 10
2 2
Found: C, 60.83; H, 3.54; N, 10.36.
Anal. Calcd. for C H N : C, 82.36; H, 5.11; N, 12.53.
23 17 3
Found: C, 82.56; H, 4.83; N, 12.47.
6-Chloro-3-(4'-bromophenyl)-3,4-dihydroquinazoline (5f).
5-Methyl-8,9-dimethoxy-2,3-diphenylimidazo[1,2-c]quinazoline
(8e).
This compound was obtained as solid with mp 187-188 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.58 (s, 1H, H2), 7.56 (d, J =
3
8.8 Hz, 2H), 7.23 (d, J = 8.4 Hz, 1H, H7), 7.17 (d, J = 8.4 Hz, 1H,
H8), 7.05 (d, J = 8.8 Hz, 2H), 7.01 (s, 1H, H5), 4.90 (s, 2H, H4);
This compound was obtained as solid with mp 254-256 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.62-7.53 (m, 9H), 7.29-7.26
3

March 2005
Synthesis of Quinazoline Derivatives With the Aid of Low-valent Titanium Reagent
179
(m, 3H), 4.04 (s, 6H, 2xCH O), 2.64(s, 3H, CH ); IR (KBr):
reagent (10 mmol) prepared as mentioned above. When the reac-
3
3
3057, 2957, 1628, 1535, 1495, 1438, 1380, 1339, 1265, 1228,
1206, 1182, 1025, 925, 784, 768, 707 cm .
tion was completed (at room temperature under N ), most of the
solvent was removed in vacuo. The residue was poured into 10%
2
-1
HCl (50 mL), and extracted with CHCl (3x50 mL). The com-
Anal. Calcd. for C H N O : C, 75.93; H, 5.35; N, 10.63.
3
25 21
3 2
bined organic layers were washed with water (3x50 mL), dried
Found: C, 75.89; H, 5.28; N, 10.81.
(Na SO ), and the solvent was removed in vacuo to give the
crude product. The crude product was recrystallized from ethanol
to give the pure product.
2
4
5-Methyl-9-chloro-2,3-diphenylimidazo[1,2-c]quinazoline (8f).
This compound was obtained as solid with mp 179-180
1
ºC; HNMR (400 MHz, CDCl ): δ = 8.66 (s, 1H), 7.76 (d, J = 8.0
3
2,2-Dimethyl-3-(4'-methylphenyl)-1,2-dihydroquinazolin-
4(3H)-one (10a).
Hz, 1H), 7.60-7.52 (m, 8H), 7.26-7.22 (m, 3H), 2.29 (s, 3H, CH );
3
IR (KBr): 3054, 1607, 1538, 1499, 1467, 1442, 1379, 1331, 1258,
-1
This compound was obtained as solid with mp 255-256 ºC;
1186, 1071, 1019, 920, 886, 871, 820, 778, 761, 703 cm .
1
HNMR (400 MHz, CDCl ): δ = 7.95 (d, J = 8.4 Hz, 1H, H5),
Anal. Calcd. for C H ClN : C, 74.69; H, 4.36; N, 11.36.
3
23 16
3
7.32 (dd, J = 8.8 Hz, J = 7.2 Hz, 1H, H7), 7.23 (d, J = 8.4 Hz,
Found: C, 74.83; H, 4.15; N, 11.29.
1
2
2H), 7.12 (d, J = 8.4 Hz, 2H), 6.87 (dd, J = 8.4 Hz, J = 7.2 Hz,
1
2
2,3-Di(4'-methylphenyl)imidazo[1,2-c]quinazoline (8g).
1H, H6), 6.67 (d, J = 8.8 Hz, 1H, H8), 2.38 (s, 3H, CH ), 1.49 (s,
3
This compound was obtained as solid with mp 227-229 ºC;
6H, 2xCH ); IR (KBr): 3305, 2973, 1627, 1575, 1519, 1489,
3
1
HNMR (400 MHz, CDCl ): δ = 8.71 (s, 1H), 8.52 (d, J = 7.6 Hz,
1464, 1433, 1399, 1378, 1277, 1225, 1175, 1107, 1022, 947, 813,
3
-1
1H), 7.95 (d, J = 8.8 Hz, 1H), 7.79-7.75 (m, 2H), 7.55 (d, J = 8.4
Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.16
(d, J = 8.4 Hz, 2H), 2.45 (s, 3H, CH ), 2.31 (s, 3H, CH ); IR
784, 755,718, 697 cm .
Anal. Calcd. for C H N O: C, 76.66; H, 6.81; N, 10.52.
17 18
2
Found: C, 76.83; H, 6.59; N, 10.63.
3
3
(KBr): 3050, 1619, 1600, 1530, 1491, 1472, 1453, 1379, 1351,
1308, 1268, 1176, 894, 835, 822, 759, 733, 704 cm .
2,2-Dimethyl-3-(4'-chlorophenyl)-1,2-dihydroquinazolin-4(3H)-
one (10b).
-1
Anal. Calcd. for C
H N : C, 82.49; H, 5.48; N, 12.03.
24 19 3
This compound was obtained as solid with mp 255-256 ºC;
Found: C, 82.56; H, 5.34; N, 11.98.
1
HNMR (400 MHz, CDCl ): δ = 7.94 (d, J = 7.2Hz, 1H, H5),
3
9-Chloro-2,3-di(4'-methylphenyl)imidazo[1,2-c]quinazoline
(8h).
7.41 (d, J = 8.4 Hz, 2H), 7.35 (dd, J = 8.4 Hz, J = 8.0 Hz, 1H,
1
2
H7), 7.19 (d, J = 8.4 Hz, 2H), 6.89 (dd, J = 8.0 Hz, J = 7.2 Hz,
1
2
This compound was obtained as solid with mp 237-239ºC;
1H, H6), 6.69 (d, J = 8.4 Hz, 1H, H8), 1.50 (s, 6H, 2xCH ); IR
3
1
HNMR (400 MHz, CDCl ): δ = 8.74 (s, 1H), 8.46 (s, 1H), 7.97
(KBr): 3307, 2972, 1628, 1518, 1489, 1465, 1433, 1398, 1377,
3
-1
(d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.55 (d, J = 8.0 Hz,
2H), 7.51 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.17 (d, J
= 8.0 Hz, 2H), 2.46 (s, 3H, CH ), 2.31 (s, 3H, CH ); IR (KBr):
1338, 1273, 1179, 1088, 1016, 872, 818, 756, 727, 696 cm .
Anal. Calcd. for C H ClN O: C, 67.02; H, 5.27; N, 9.77.
16 15
2
Found: C, 67.18; H, 5.03; N, 9.83.
3
3
3040, 1603, 1530, 1500, 1468, 1377, 1345, 1174, 1078, 900, 821,
734 cm .
2,2-Dimethyl-3-(4'-bromophenyl)-1,2-dihydroquinazolin-4(3H)-
one (10c).
-1
Anal. Calcd. for C H ClN : C, 75.09; H, 4.73; N, 10.95.
24 18
3
This compound was obtained as solid with mp 264-265 ºC;
Found: C, 75.21; H, 4.66; N, 11.06.
1
HNMR (400 MHz, CDCl ): δ = 7.94 (d, J = 8.0 Hz, 1H, H5),
3
2,3-Di(4'-bromophenyl)imidazo[1,2-c]quinazoline (8i).
756 (d, J = 8.0 Hz, 2H), 7.34 (dd, J = 8.0 Hz, J = 7.2 Hz, 1H,
1
2
This compound was obtained as solid with mp 239-240 ºC;
H7), 7.13 (d, J = 8.0 Hz, 2H), 6.88 (dd, J = 8.0 Hz, J = 7.2 Hz,
1 2
1
HNMR (400 MHz, CDCl ): δ = 8.81 (s, 1H), 7.80 (d, J = 8.4 Hz,
1H, H6), 6.68 (d, J = 8.0 Hz, 1H, H8), 1.49 (s, 6H, 2xCH ); IR
3
3
1H), 7.97 (d, J = 8.4 Hz, 1H), 7.84-7.77 (m, 5H), 7.62-7.59 (m,
5H); IR (KBr): 3050, 1613, 1530, 1493, 1471, 1396, 1374, 1351,
1301, 1261, 1175, 1121, 1009, 959, 894, 827, 732 cm .
(KBr): 3307, 2968, 1627, 1579, 1489, 1465, 1433, 1397, 1377,
1271, 1171, 1098, 1067, 1012, 871,756,696 cm .
-1
-1
Anal. Calcd. for C H BrN O: C, 58.02; H, 4.56; N, 8.46.
16 15 2
Anal. Calcd. for C H Br N : C, 55.14; H, 2.73; N, 8.77.
Found: C, 58.18; H, 4.54; N, 8.65.
22 13
2 3
Found: C, 55.32; H, 2.64; N, 8.54.
7-Chloro-2,2-dimethyl-3-phenyl-1,2-dihydroquinazolin-4(3H)-
one (10d).
9-Chloro-2,3-di(4'-bromophenyl)imidazo[1,2-c]quinazoline (8j).
This compound was obtained as solid with mp 248-250 ºC;
This compound was obtained as solid with mp 270-272 ºC;
1
1
HNMR (400 MHz, CDCl ): δ = 7.87 (d, J = 8.4 Hz, 1H, H5),
HNMR (400 MHz, CDCl ): δ = 8.83 (s, 1H), 8.48 (s, 1H), 7.99
3
3
7.55-7.22 (m, 5H), 6.83 (d, J = 8.4 Hz, 1H H6), 6.68 (s, 1H, H8),
(d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.4 Hz, 2H), 7.65-7.54 (m, 7H);
IR (KBr): 3050, 1608, 1358, 1494, 1469, 1397, 1375, 1345,
1124, 1079, 1009, 900, 821, 734, 715 cm .
1.49 (s, 6H, 2xCH ); IR (KBr): 3286, 2968, 1628, 1606, 1516,
3
-1
1488, 1454, 1411, 1389, 1371 1279, 1224, 1178, 1077, 1032,
-1
1002, 988, 950, 931, 898, 850, 809, 758, 733, 699 cm .
Anal. Calcd. for C H Br ClN : C, 51.45; H, 2.35; N, 8.18.
22 12
2
3
Anal. Calcd. for C H ClN O: C, 67.02; H, 5.27; N, 9.77.
Found: C, 51.68; H, 2.28; N, 8.40.
16 15
2
Found: C, 67.25; H, 5.18; N, 9.69.
General Procedure for the Synthesis of 1,2-Dihydroquinazolin-
7-Chloro-2,2-dimethyl-3-(4'-methylphenyl)-1,2-dihydroquina-
4(3H)-ones.
zolin-4(3H)-one (10e).
A solution of o-nitrobenzamide 1 (3 mmol) and ketone or alde-
hyde 9 (3 mmol) in anhydrous THF (10 mL) was added carefully
at room temperature to a suspension of low-valent titanium
This compound was obtained as solid with mp 278-280 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.87 (d, J = 8.0 Hz, 1H, H5),
3

180
D. Shi, C. Shi, J. Wang, L. Rong, Q. Zhuang, and X. Wang
Vol. 42
-1
7.23 (d, J = 7.2 Hz, 2H), 7.10 (d, J = 7.2 Hz, 2H), 6.82 (d, J = 8.0
1512, 1489, 1430, 1395, 1331, 1275, 1182, 1153, 758 cm .
Hz, 1H H6), 6.67 (s, 1H, H8), 2.38 (s, 3H, CH ), 1.49 (s, 6H,
Anal. Calcd. for C H N O: C, 69.45; H, 7.42; N, 14.73.
3
11 14
2
2xCH ); IR (KBr):3300, 2971, 1633, 1510, 1484, 1457, 1413,
Found: C, 69.58; H, 7.14; N, 14.89.
3
1366, 1284, 1258, 1175, 1106, 1077, 1025, 992, 901, 849, 811,
786, 765, 709, 693 cm .
2,2-Diethyl-1,2-dihydroquinazolin-4(3H)-one (10k).
This compound was obtained as solid with mp 190-191 ºC;
-1
Anal. Calcd. for C H ClN O: C, 67.88; H, 5.70; N, 9.31.
17 17
2
1
HNMR (400 MHz, CDCl ): δ = 7.85 (d, J = 8.0 Hz, 1H, H5),
Found: C, 67.93; H, 5.54; N, 9.49.
3
7.28 (dd, J = 8.0 Hz, J = 8.0 Hz, 1H, H7), 6.78 (dd, J = 8.0 Hz,
1
2
1
7-Chloro-2,2-dimethyl-3-(4'-bromophenyl)-1,2-dihydroquina-
zolin-4(3H)-one (10f).
J = 8.0 Hz, 1H, H6), 6.60 (d, J = 8.0 Hz, 1H, H8), 5.98 (br s, 1H,
2
NH), 1.76 (q, J = 8.0 Hz, 4H, 2xCH ), 0.97 (t, J = 8.0 Hz, 6H,
2
This compound was obtained as solid with mp 270-272 ºC;
2xCH ); IR (KBr):3320, 3175, 2974, 1646, 1607, 1510, 1489,
1463, 1429, 1395, 1329, 1274, 1150, 758 cm .
3
1
-1
HNMR (400 MHz, CDCl ): δ = 7.86 (d, J = 8.0 Hz, 1H, H5),
3
7.57 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 6.84 (d, J = 8.0
Anal. Calcd. for C H N O: C, 70.56; H, 7.90; N, 13.71.
12 16 2
Hz, 1H H6), 6.69 (s, 1H, H8), 1.49 (s, 6H, 2xCH ); IR (KBr):
Found: C, 70.83; H, 7.84; N, 13.62.
3
3297, 2965, 1625, 1515, 1486, 1455, 1409, 1372, 1279, 1174,
1097, 1068, 1023, 1010, 903, 856, 814, 768, 715, 695 cm .
7-Chloro-2-methyl-2-ethyl-1,2-dihydroquinazolin-4(3H)-one
(10l).
-1
Anal. Calcd. for C H BrClN O: C, 52.56; H, 3.86; N, 7.66.
16 14
2
This compound was obtained as solid with mp 173-174 ºC;
Found: C, 52.68; H, 3.74; N, 7.54.
1
HNMR (400 MHz, CDCl ): δ = 7.78 (d, J = 8.0 Hz, 1H, H5),
3
2,2-Dimethyl-3-(n-octyl)-1,2-dihydroquinazolin-4(3H)-one (10g).
This compound was obtained as solid with mp 110-112 ºC;
6.96 (br s, 1H, NH), 6.75 (d, J = 8.0, 1H, H6), 6.63 (s, 1H, H8),
1.79 (q, J = 8.0 Hz, 2H, CH ), 1.50 (s, 3H, CH ), 0.98 (t, J = 8.0
2
3
1
HNMR (400 MHz, CDCl ): δ = 7.90 (d, J = 7.2 Hz, 1H, H5),
Hz, 3H, CH ); IR (KBr):3304, 3191, 2974, 1642, 1608, 1510,
3
3
-1
7.21 (dd, J = 7.6 Hz, J = 8.0 Hz, 1H, H7), 6.72 (dd, J = 7.2 Hz,
1480, 1454, 1419, 1320, 1276, 1156, 1079, 896, 854, 778 cm .
1
2
1
J = 7.6 Hz, 1H, H6), 6.60 (d, J = 8.0 Hz, 1H, H8), 3.48-3.38 (m,
Anal. Calcd. for C H ClN O: C, 58.80; H, 5.83; N, 12.47.
2
11 13
2
2H, CH N), 1.66-1.56 (m, 2H, CH ), 1.55 (s, 6H, 2xCH ), 1.40-
Found: C, 58.92; H, 5.71; N, 12.56.
2
2
3
1.23 (m, 10H, 5xCH ), 0.92-0.85 (m, 3H, CH ); IR (KBr):3281,
2
3
7-Chloro-2,2-diethyl-1,2-dihydroquinazolin-4(3H)-one (10m).
2925, 2851, 1621, 1517, 1487, 1465, 1434, 1401, 1367, 1352,
-1
1326, 1282, 1191, 1148, 1029, 752, 699 cm .
This compound was obtained as solid with mp 164-166 ºC;
1
Anal. Calcd. for C
H
N O: C, 74.96; H, 9.78; N, 9.71.
HNMR (400 MHz, CDCl ): δ = 7.76 (d, J = 8.0 Hz, 1H, H5),
18 28
2
3
6.71 (d, J = 8.0 Hz, 1H, H6), 6.61 (s, 1H, H8), 6.59 (br s, 1H,
Found: C, 75.03; H, 9.57; N, 9.62.
NH),1.75 (q, J = 8.0 Hz, 4H, 2xCH ), 0.96 (t, J = 8.0 Hz, 6H,
2
7-Chloro-2,2-dimethyl-3-(n-octyl)-1,2-dihydroquinazolin-
4(3H)-one (10h).
2xCH ); IR (KBr):3286, 3215, 2967, 1644, 1608, 1513, 1483,
3
1461, 1420, 1363, 1324, 1276, 1175, 1155, 1082, 986, 912, 874,
-1
This compound was obtained as solid with mp 110-111 ºC;
774 cm .
1
HNMR (400 MHz, CDCl ): δ = 7.82 (d, J = 8.4 Hz, 1H, H5),
Anal. Calcd. for C H ClN O: C, 60.38; H, 6.33; N, 11.74.
3
12 15
2
7.21 (d, J = 8.4 Hz, 1H, H6), 6.68 (s, 1H, H8), 3.45-3.35 (m, 2H,
Found: C, 60.51; H, 6.31; N, 11.59.
CH N), 1.65-1.58 (m, 2H, CH ), 1.55 (s, 6H, 2xCH ), 1.38-1.22
2
2
3
2-(4'-Methylphenyl)-1,2-dihydroquinazolin-4(3H)-one (10n).
(m, 10H, 5xCH ), 0.92-0.85 (m, 3H, CH ); IR (KBr): 3299,
2
3
2960, 2928, 2854, 1623, 1516, 1468, 1417, 1367, 1324, 1279,
1181, 1079, 987, 847, 768, 693 cm .
This compound was obtained as solid with mp 231-233 ºC;
-1
1
HNMR (400 MHz, CDCl ): δ = 7.94 (d, J = 7.2 Hz, 1H, H5),
3
Anal. Calcd. for C H ClN O: C, 66.96; H, 8.43; N, 8.68.
7.48 (d, J = 8.0 Hz, 2H), 7.34 (dd, J = 8.4 Hz, J =8.4 Hz, 1H,
18 27
2
1 2
H7), 7.25 (d, J = 8.0 Hz, 2H ), 6.90 (dd, J = 8.4 Hz, J = 7.2 Hz,
Found: C, 67.21; H, 8.27; N, 8.56.
1
2
1H, H6), 6.67 (d, J = 8.4 Hz, 1H, H8), 5.87 (s, 1H, H2), 5.78 (br
2,2-Dimethyl-3-benzyl-1,2-dihydroquinazolin-4(3H)-one (10i).
This compound was obtained as solid with mp 200-201 ºC;
s, 1H, NH), 2.40 (s, 3H, CH ); IR (KBr): 3312, 3194, 1657, 1611,
3
1509, 1486, 1438, 1385, 1328, 1297, 1151, 1133, 1022, 948, 909,
1
-1
HNMR (400 MHz, CDCl ): δ = 7.98 (d, J = 7.2 Hz, 1H, H5),
859, 800, 751 cm .
3
7.30-7.23 (m, 5H), 7.22 (dd, J = 7.6 Hz, J = 8.4 Hz, 1H, H7),
Anal. Calcd. for C H N O: C, 75.61; H, 5.92; N, 11.76.
1
2
15 14
2
6.87 (dd, J = 7.2 Hz, J = 7.6 Hz, 1H, H6), 6.64 (d, J = 8.4 Hz,
Found: C, 75.82; H, 5.74; N, 11.85.
1
2
1H, H8), 4.82 (s, 2H, CH2), 1.55 (s, 6H, 2xCH ); IR (KBr): 3321,
3
2-(3',4'-Methylenedioxylphenyl)-1,2-dihydroquinazolin-4(3H)-
one (10o).
3030, 2997, 2927, 1625, 1514, 1458, 1364, 1284, 1179, 1073,
-1
1025, 918, 858, 756, 694 cm .
This compound was obtained as solid with mp 199-201 ºC;
Anal. Calcd. for C H N O: C, 76.66; H, 6.81; N, 10.52.
Found: C, 76.59; H, 7.05; N, 10.67.
17 18
2
1
HNMR (400 MHz, CDCl ): δ = 7.94 (d, J = 7.2 Hz, 1H, H5),
3
7.34 (dd, J = 7.6 Hz, J = 8.4 Hz, 1H, H7), 7.15 (s, 1H), 6.99 (d,
1
2
2-Methyl-2-ethyl-1,2-dihydroquinazolin-4(3H)-one (10j).
This compound was obtained as solid with mp 184-186 ºC;
J = 8.0 Hz, 1H), 6.91 (dd, J = 7.2 Hz, J = 7.6 Hz, 1H, H6), 6.83
1
2
(d, J = 8.0 Hz, 1H), 6.67 (d, J = 8.0 Hz, 1H, H8), 6.02 (s, 2H,
1
OCH O), 5.82 (s, 1H, H2), 5.80 (br s, 1H, NH); IR (KBr):3282,
HNMR (400 MHz, CDCl ): δ = 7.87 (d, J = 8.0 Hz, 1H, H5),
2
3
3181, 1654, 1612, 1486, 1446, 1388, 1327, 1297, 1248, 1187,
1164, 1149, 1121, 1105, 1036, 930, 864, 786, 754 cm .
7.30 (dd, J = 8.0 Hz, J = 7.2 Hz, 1H, H7), 6.81 (dd, J = 8.0 Hz,
1
2
1
-1
J = 7.2 Hz, 1H, H6), 6.62 (d, J = 8.0 Hz, 1H, H8), 6.16 (br s, 1H,
2
Anal. Calcd. for C H N O : C, 67.16; H, 4.51; N, 10.44.
NH), 1.81 (q, J = 8.0 Hz, 2H, CH ), 1.50 (s, 3H, CH ), 0.99 (t, J
15 12
2 3
2
3
Found: C, 67.27; H, 4.38; N, 10.49.
= 8.0 Hz, 3H, CH ); IR (KBr):3279, 3178, 2974, 1643, 1609,
3

March 2005
Synthesis of Quinazoline Derivatives With the Aid of Low-valent Titanium Reagent
181
7-Chloro-2-(4'-methylphenyl)-1,2-dihydroquinazolin-4(3H)-one
(10p).
This compound was obtained as solid with mp 221-222 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.79 (d, J = 8.8 Hz, 1H, H5),
3
6.77 (d, J = 8.8 Hz, 1H, H6), 6.66 (s, 1H, H8), 6.17 (br s, 1H,
NH), 1.83-1.78 (m, 4H, 2xCH ), 1.67-1.53 (m, 4H, 2xCH ),
This compound was obtained as solid with mp 242-244 ºC;
1
2
2
HNMR (400 MHz, CDCl ): δ = 7.87 (d, J = 8.8 Hz, 1H, H5),
3
1.49-1.45 (m, 2H, CH ); IR (KBr): 3362, 3249, 1699, 1600,
2
7.45 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.8
Hz, 1H, H6), 6.67 (s, 1H, H8 ), 5.87 (s, 1H, H2), 5.78 (br s,1H,
-1
1576, 1507, 1464, 1336, 1152, 1044, 890, 751 cm .
Anal. Calcd. for C H ClN O: C, 62.28; H, 6.03; N, 11.17.
13 15
2
NH), 2.40 (s, 3H, CH ); IR (KBr): 3294, 3181, 1654, 1606, 1510,
3
Found: C, 62.43; H, 5.96; N, 11.33.
1471, 1432, 1370, 1297, 1172, 1133, 1079, 1014, 922, 858, 816,
-1
748, 721, 678 cm .
General Procedure for the Synthesis of 5,6-Dihydroimidazo[1,2-c]-
Anal. Calcd. for C H ClN O: C, 66.06; H, 4.80; N, 10.27.
quinazolines.
15 13
2
Found: C, 66.24; H, 4.76; N, 10.19.
A solution of 2-(o-nitrophenyl)imidazole 6 (3 mmol) and
ketone or aldehyde 9 (3 mmol) in anhydrous THF (10 mL) was
added carefully at room temperature to a suspension of low-
valent titanium reagent (10 mmol) prepared as mentioned above.
When the reaction was completed (at room temperature under
7-Chloro-2-(4'-methoxyphenyl)-1,2-dihydroquinazolin-4(3H)-
one (10q).
This compound was obtained as solid: with mp 215-216 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.86 (d, J = 8.8 Hz, 1H, H5),
3
N ), most of the solvent was removed in vacuo. The residue was
2
7.51 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.0
Hz, 1H, H6), 6.67 (s, 1H, H8), 5.86 (s, 1H, H2), 5.77 (br s, 1H,
poured into 10% HCl (50 mL), and extracted with CHCl (3_50
3
mL). The combined organic layers were washed with water
NH), 3.85 (s, 3H, CH O); IR (KBr): 3295, 3185, 1654, 1610,
3
(3x50 mL), dried (Na SO ), and the solvent was removed in
2
4
1510, 1480, 1427, 1369, 1294, 1254, 1171, 1135, 1110, 1079,
1038, 923, 863, 834, 782, 748, 680 cm .
vacuo to give the crude product. The crude product was purified
by column chromatography on silica gel (200-300 mesh) using
petroleum ether (b.p. 60-90 ºC) – acetone (5:1) as eluent.
-1
Anal. Calcd. for C H ClN O : C, 62.40; H, 4.54; N, 9.70.
15 13
2 2
Found: C, 62.56; H, 4.32; N, 9.81.
5,5-Dimethyl-2,3-diphenyl-5,6-dihydroimidazo[1,2-c]quinazo-
line (13a).
2,2-Tetramethylene-1,2-dihydroquinazolin-4(3H)-one (12a).
This compound was obtained as solid with mp 251-253 ºC;
This compound was obtained as solid with mp 240-241 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.88 (d, J = 7.2 Hz, 1H, H5),
3
1
HNMR (400 MHz, CDCl ): δ = 7.84 (d, J = 7.2 Hz, 1H), 7.51-7.54
3
7.31 (dd, J = 8.4 Hz, J = 7.2 Hz, 1H, H7), 6.85 (dd, J = 7.2
1
2
1
(m, 5H), 7.36 (d, J = 7.2 Hz, 2H), 7.08-7.19 (m, 4H), 6.83 (d, J = 7.2
Hz, 1H), 6.79 (d, J = 8.8 Hz, 1H), 6.52 (br s, 1H, NH), 1.36 (s, 6H,
Hz, J = 7.2 Hz, 1H, H6), 6.65 (d, J = 8.4 Hz, 1H, H8), 6.17 (br
2
s, 1H, NH), 1.97-1.88 (m, 4H, 2xCH ), 1.80-1.79 (m, 4H,
2
2xCH ); IR (KBr): 3240, 3012, 2979, 1614, 1512, 1479, 1444,
3
CH CH ); IR (KBr): 3292, 3159, 2972, 1638, 1606, 1517,
2
2
-1
1367, 1275, 1211, 1161, 1072, 964, 916, 791, 772, 752, 698 cm .
1485, 1431, 1385, 1334, 1270, 1149, 1088, 1049, 954, 849,
Anal. Calcd. for C
H N : C, 82.02; H, 6.02; N, 11.96.
-1
24 21 3
803, 781, 753 cm .
Found: C, 82.25; H, 5.89; N, 12.10.
Anal. Calcd. for C H N O: C, 71.26; H, 6.98; N, 13.85.
12 14
2
Found: C, 71.38; H, 6.71; N, 14.02.
5,5-Dimethyl-9-chloro-2,3-diphenyl-5,6-dihydroimidazo[1,2-c]-
quinazoline (13b).
2,2-Pentamethylene-1,2-dihydroquinazolin-4(3H)-one (12b).
This compound was obtained as solid with mp 228-229 ºC;
This compound was obtained as solid with mp 224-225 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.77 (s, 1H), 7.58-7.48 (m, 5H),
3
1
HNMR (400 MHz, CDCl ): δ = 7.87 (d, J = 7.6 Hz, 1H, H5),
3
7.36 (d, J = 7.6 Hz, 2H), 7.21-7.10 (m, 4H), 6.80 (d, J = 8.4 Hz,
7.30 (dd, J = 8.4Hz, J = 7.2 Hz, 1H, H7), 6.82 (dd, J = 7.6 Hz
1
2
1
1H), 6.76 (br s, 1H, NH), 1.35 (s, 6H, 2xCH ); IR (KBr): 3247,
3
J = 7.2 Hz, 1H, H6), 6.65 (d, J = 8.4 Hz, 1H, H8), 6.19 (br s, 1H,
2
3087, 2979, 1603, 1557, 1525, 1508, 1477, 1444, 1389, 1368,
NH), 1.84-1.80 (m, 4H, 2xCH ), 1.60-1.53 (m, 4H, 2xCH ),
2
2
-1
1309, 1226, 1161, 814, 774, 697 cm .
1.48-1.47 (m, 2H, CH ); IR (KBr): 3367, 3170, 2923, 1651,
2
Anal. Calcd. for C H ClN : C, 74.70; H, 5.22; N, 10.89.
24 20
3
1612, 1507, 1484, 1417, 1382, 1269, 1210, 1178, 1145, 1093,
Found: C, 74.82; H, 5.06; N, 10.96.
-1
1040, 1004, 951, 914, 855, 802, 760 cm .
Anal. Calcd. for C H N O: C, 72.19; H, 7.46; N, 12.95.
5,5-Dimethyl-8,9-methylenedioxy-2,3-diphenyl-5,6-dihydroimi-
13 16
2
Found: C, 72.32; H, 7.28; N, 13.15.
dazo[1,2-c]quinazoline (13c).
This compound was obtained as solid with mp 239-240 ºC;
7-Chloro-2,2-tetramethylene-1,2-dihydroquinazolin-4(3H)-one
(12c).
1
HNMR (400 MHz, CDCl ): δ = 7.48-7.53 (m, 5H), 7.33 (d, J =
3
7.2 Hz, 2H), 7.29 (s, 1H), 7.16-7.06 (m, 3H), 6.41 (s, 1H), 6.32
This compound was obtained as solid with mp 223-225 ºC;
(br s, 1H, NH), 5.97 (s, 2H, CH ), 1.31 (s, 6H, 2xCH ). IR (KBr):
2
3
1
HNMR (400 MHz, CDCl ): δ = 7.80 (d, J = 8.8 Hz, 1H, H5),
3
3230, 2976, 1626, 1502, 1469, 1354, 1265, 1198, 1148, 1039,
6.80 (d, J = 8.8 Hz, 1H, H6), 6.65 (s, 1H, H8), 6.23 (br s, 1H,
-1
941, 864, 831, 781, 700 cm .
NH), 1.96-1.81 (m, 4H, 2_CH ), 1.80-1.62 (m, 4H, 2xCH ); IR
2
2
Anal. Calcd. for C H N O : C, 75.93; H, 5.35; N, 10.63.
25 21
3 2
(KBr): 3260, 3189, 1650, 1608, 1519, 1480, 1421, 1361, 1318,
Found: C, 76.03; H, 5.28; N, 10.55.
-1
1277, 1154, 1078, 1044, 936, 899, 855, 768 cm .
Anal. Calcd. for C H ClN O: C, 60.98; H, 5.54; N, 11.84.
Found: C, 61.02; H, 5.36; N, 11.97.
5,5-Dimethyl-2,3-di(4'-methylphenyl)-5,6-dihydroimidazo[1,2-c]-
quinazoline (13d).
12 13
2
This compound was obtained as solid with mp 222-224 ºC;
7-Chloro-2,2-pentamethylene-1,2-dihydroquinazolin-4(3H)-one
(12d).
1
HNMR (400 MHz, CDCl ): δ = 7.81 (d, J = 7.6 Hz, 1H), 7.40-
3

182
D. Shi, C. Shi, J. Wang, L. Rong, Q. Zhuang, and X. Wang
Vol. 42
7.14 (m, 7H), 6.97 (d, J = 8.4 Hz, 2H), 6.96-6.77 (m, 2H), 6.52
(br s, 1H, NH), 2.42 (s, 3H, CH ), 2.21 (s, 3H, CH ), 1.34 (s, 6H,
2H), 7.31 (d, J = 8.8 Hz, 2H), 7.17 (d, J = 8.4 Hz, 1H), 7.07 (d, J
= 8.8 Hz, 2H), 6.80-6.75 (m, 4H), 6.74 (br s, 1H, NH), 3.84 (s,
3
3
2xCH ); IR (KBr): 3224, 3012, 1613, 1513, 1500, 1490, 1388,
3H, CH3), 3.69 (s, 3H, CH3), 1.35 (s, 6H, 2xCH ); IR (KBr):
3
3
1367, 1311, 1278, 1232, 1211, 1167, 1107, 1022, 968, 824, 754,
705 cm .
3389, 1611, 1530, 1493, 1385, 1367, 1238, 1107, 1029, 966, 879,
841, 803, 774, 745, 713, 681 cm .
-1
-1
Anal. Calcd. for C
H N : C, 82.29; H, 6.64; N, 11.07.
26 25 3
Anal. Calcd. for C H ClN O : C, 70.03; H, 5.42; N, 9.42.
26 24
3 2
Found: C, 82.17; H, 6.75; N, 11.23.
Found: C, 70.18; H, 5.27; N, 9.53.
5,5-Dimethyl-2,3-di(4'-methylphenyl)-9-chloro-5,6-dihydroimi-
5,5-Dimethyl-2,3-di(4'-fluorophenyl)-5,6-dihydroimidazo[1,2-
dazo[1,2-c]quinazoline (13e).
c]quinazoline (13j).
This compound was obtained as solid with mp 215-217 ºC;
This compound was obtained as solid with mp 261-262 ºC;
1
1
HNMR (400 MHz, CDCl ): δ = 7.73 (d, J = 8.8 Hz, 1H), 7.32-
HNMR (400 MHz, CDCl ): δ = 7.83 (d, J = 7.6 Hz, 1H), 7.57
3
3
7.24 (m, 5H), 7.19 (d, J = 7.6 Hz, 1H), 7.04 (d, J = 8.4 Hz, 1H),
6.98 (d, J = 8.0 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H), 6.79 (d, J = 8.4
(dd, J = 8.8 Hz, J = 5.6 Hz, 2H), 7.39-7.34 (m, 4H), 7.20-7.15
1
2
(m, 1H), 7.04 (dd, J = 8.8 Hz, J = 5.6 Hz, 2H), 6.83 (d, J = 7.6
1
2
Hz, 1H), 6.75 (br s, 1H, NH), 2.42 (s, 3H, CH ), 2.21(s, 3H,
Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 6.58 (br s, 1H, NH), 1.36 (s, 6H,
3
CH ), 1.35 (s, 6H, 2xCH ); IR (KBr): 3212, 1613, 1508, 1490,
2xCH ). IR (KBr): 3416, 2987, 1619, 1595, 1538, 1485, 1385,
1364, 1321, 1279, 1214, 1159, 855, 843, 818, 748, 703 cm .
3
3
3
-1
1389, 1369, 1306, 1258, 1229, 1205, 1163, 1108, 1083, 1019,
-1
971, 813, 767, 738, 678 cm .
Anal. Calcd. for C H F N : C, 74.40; H, 4.94; N, 10.85.
24 19
2 3
Anal. Calcd. for C H ClN : C, 75.44; H, 5.84; N, 10.15.
Found: C, 74.37; H, 4.89; N, 11.03.
26 24
3
Found: C, 75.59; H, 5.66; N, 10.37.
5-(4'-Methylphenyl)-2,3-diphenyl-5,6-dihydroimidazo[1,2-c]-
quinazoline (13k).
5,5-Dimethyl-2,3-di(4'-bromophenyl)-5,6-dihydroimidazo[1,2-
c]quinazoline (13f).
This compound was obtained as solid with mp 239-240 ºC;
1
This compound was obtained as solid with mp 262-264 ºC;
HNMR (400 MHz, CDCl ): δ = 7.52-7.51 (m, 5H), 7.40-7.38
3
1
HNMR (400 MHz, CDCl ): δ = 7.83 (d, J = 7.6 Hz, 1H), 7.74
(m, 2H), 7.33-7.31 (m, 5H), 7.21-7.12 (m, 4H), 6.98-6.78 (m,
3
(d, J = 8.4 Hz, 1H), 7.50-7.40 (m, 6H), 7.27 (d, J = 8.4 Hz, 1H),
7.17 (d, J = 7.2 Hz, 1H), 6.83 (d, J = 7.6 Hz, 1H), 6.79 (d, J = 7.2
1H), 6.75-6.77 (m, 1H), 4.47 (s, 1H), 2.42 (s, 3H, CH ); IR
3
(KBr): 3367, 3055, 2920, 1609, 1584, 1535, 1517, 1505, 1477,
-1
Hz, 1H), 6.61 (br s, 1H, NH), 1.39 (s, 6H, 2xCH ); IR (KBr):
1441, 1334, 1306, 1283, 1067, 817, 765, 739, 714, 695 cm .
3
3354, 3050, 1610, 1532, 1496, 1401, 1328, 1152, 1098, 1079,
1009, 969, 810, 748, 717 cm .
Anal. Calcd. for C
Found: C, 84.46; H, 5.38; N, 10.24.
H N : C, 84.23; H, 5.61; N, 10.16.
29 23 3
-1
Anal. Calcd. for C H Br N : C, 56.61; H, 3.76; N, 8.25.
Found: C, 56.83; H, 3.51; N, 8.09.
24 19
2 3
5-(3',4'-Dimethoxyphenyl)-2,3-diphenyl-5,6-dihydroimi-
dazo[1,2-c]quinazoline (13l).
5,5-Dimethyl-2,3-di(4'-bromophenyl)-9-chloro-5,6-dihydroimi-
dazo[1,2-c]quinazoline (13g).
This compound was obtained as solid with mp 237-239 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.51-7.37 (m, 11H), 7.17-7.14
3
This compound was obtained as solid with mp 286-288 ºC;
(m, 3H), 7.02 (s, 1H), 6.87 (d, J = 8.0 Hz, 1H), 6.70 (d, J = 8.0 Hz,
1
HNMR (400 MHz, CDCl ): δ = 7.74 (d, J = 8.4 H, 2H), 7.50-7.45
1H), 4.44 (s, 1H),3.91 (s, 3H, CH O), 3.80 (s, 3H, CH O); IR
3
3
3
(m, 3H), 7.42 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 8.8 Hz, 2H), 7.22 (d,
J = 8.4 Hz, 1H), 6.83 (br s, 1H, NH), 6.81 (d, J = 8.4 Hz, 1H), 1.41
(KBr): 3241, 3066, 2982, 1611, 1512, 1476, 1443, 1386, 1371,
1312, 1277, 1229, 1211, 1164, 1029, 967, 770, 752, 722, 700 cm .
-1
(s, 6H, 2xCH ); IR (KBr): 3390, 3012, 2973, 1610, 1592, 1536,
1491, 1387, 1307, 1195, 1167, 1099, 1070, 1009, 829 cm .
Anal. Calcd. for C H N O : C, 78.41; H, 5.48; N, 9.14.
Found: C, 78.57; H, 5.23; N, 9.29.
3
30 25
3 2
-1
Anal. Calcd. for C H Br ClN : C, 53.02; H, 3.34; N, 7.73.
Found: C, 53.26; H, 3.15; N, 7.96.
24 18
2
3
5-(4'-Methylphenyl)-2,3-diphenyl-9-chloro-5,6-dihydroimi-
dazo[1,2-c]quinazoline (13m).
5,5-Dimethyl-2,3-di(4'-methoxyphenyl)-5,6-dihydroimi-
dazo[1,2-c]quinazoline (13h).
This compound was obtained as solid with mp 217-218 ºC;
1
HNMR (400 MHz, CDCl ): δ = 7.55-7.42 (m, 6H), 7.25-7.00
3
This compound was obtained as solid with mp 187-189 ºC;
(m, 7H), 6.89 (d, J = 8.0 Hz, 1H), 6.81 (d, J = 8.4 Hz, 1H), 6.39
1
HNMR (400 MHz, CDCl ): δ = 7.82 (d, J = 7.2 Hz, 1H), 7.44
(d, J = 7.2 Hz, 2H), 4.29 (s, 1H), 2.18 (s, 3H, CH ); IR (KBr):
3
3
(d, J = 8.8 Hz, 2H), 7.38 (d, J = 8.4 Hz, 1H), 7.31 (d, J = 8.0 Hz,
1H), 7.14 (t, J = 7.2 Hz, 1H), 7.08-7.05 (m, 2H), 6.82 (d, J = 7.2
Hz, 1H), 6.77 (d, J = 8.4 Hz, 2H), 6.58 (t, J = 7.2 Hz, 1H), 6.53
(br s, 1H, NH), 3.84 (s, 3H, CH O), 3.69 (s, 3H, CH O), 1.35 (s,
3265, 3066, 2951, 1608, 1529, 1496, 1443, 1118, 1065, 1015,
887, 815, 775, 698 cm .
-1
Anal. Calcd. for C
H ClN : C, 77.76; H, 4.95; N, 9.38.
29 22 3
Found: C, 77.85; H, 4.81; N, 9.25.
3
3
6H, 2xCH ); IR (KBr): 3305, 1613, 1540, 1489, 1384, 1363,
1287, 1176, 1106, 1030, 966, 837, 742 cm .
3
5-(4'-Methoxylphenyl)-2,3-diphenyl-9-chloro-5,6-dihydroimi-
dazo[1,2-c]quinazoline (13n).
-1
Anal. Calcd. for C H N O : C, 75.89; H, 6.12; N, 10.21.
26 25
3 2
This compound was obtained as solid with mp 206-207 ºC;
Found: C, 75.94; H, 5.96; N, 10.37.
1
HNMR (400 MHz, CDCl ): δ = 7.58-7.49 (m, 6H), 7.41-7.32
3
5,5-Dimethyl-2,3-di(4'-methoxyphenyl)-5,6-dihydroimi-
dazo[1,2-c]quinazoline (13i).
(m, 7H), 7.08 (d, J = 8.4 Hz, 2H), 6.73 (d, J = 8.0 Hz, 2H), 4.43
(s, 1H), 3.84 (s, 3H, CH O); IR (KBr): 3455, 3057, 2925, 1612,
3
This compound was obtained as solid with mp 196-197 ºC;
1500, 1442, 1323, 1250, 1155, 1072, 1028, 971, 916, 860, 813,
769, 697 cm .
1
-1
HNMR (400 MHz, CDCl ): δ =7 .74 (s, 1H), 7.39 (d, J = 8.8 Hz,
3

March 2005
Synthesis of Quinazoline Derivatives With the Aid of Low-valent Titanium Reagent
183
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Found: C, 75.26; H, 4.59; N, 9.13.
29 22
3
Acknowledgments.
We thank the Natural Science Foundation of Jiangsu
Education Department (No. 03KJB150136) and the Foundation
of Key Laboratory of Biotechnology on Medical Plant of Jiangsu
Province (No.02AXL13) for financial support.
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