A convenient one-pot procedure for the synthesis of 2-aryl quinazolines using active MnO2 as oxidant

Article abstract of DOI:10.1002/jhet.444

(Chemical Equation Presented) A variety of 2-aryl quinazolines were synthesized from the condensation of 2-aminobenzylamines and aryl aldehydes to form 2-aryl-1,2,3,4-tetrahydroquinazolines and subsequent oxidation of the intermediates with MnO₂

Full text of DOI:10.1002/jhet.444

1240
A Convenient One-Pot Procedure for the Synthesis of 2-Aryl
Quinazolines Using Active MnO2 as Oxidant
Vol 47
Yi-Yuan Peng,a* Yuyun Zeng,a Ganyinsheng Qiu,a Lisheng Cai,b
and Victor W. Pikeb
aKey Laboratory of Green Chemistry, Department of Chemistry, Jiangxi Normal University,
Nanchang, Jiangxi 330022, China
bPET Radiopharmaceutical Sciences Section, Molecular Imaging Branch, National Institute of
Mental Health, National Institutes of Health, Building 10, Room B3C346, 10 Center Drive,
Bethesda, Maryland 20892
*E-mail: yiyuanpeng@yahoo.com
Received December 12, 2009
DOI 10.1002/jhet.444
Published online 26 July 2010 in Wiley Online Library (wileyonlinelibrary.com).
A variety of 2-aryl quinazolines were synthesized from the condensation of 2-aminobenzylamines
and aryl aldehydes to form 2-aryl-1,2,3,4-tetrahydroquinazolines and subsequent oxidation of the inter-
mediates with MnO2.
J. Heterocyclic Chem., 47, 1240 (2010).
INTRODUCTION
tures [30,31], alkali media [32,33], H2O [34], and ionic
liquids [35]. Vandeneynde et al. reported alternative
methods where aldehydes were converted, in situ, to N-
(1-chloroalkyl)pyridinium, which reacted with 2-amino-
benzylamine to yield tetrahydroquinazoline hydrochlor-
ide salts 3ꢀHCl [36]. Two oxidation regents were used
to oxidize 2-aryl-tetrahydroquinazolines to the corre-
sponding quinazolines 4. One is 2,3-dichloro-5,6-dicya-
nobenzoquinone (DDQ) and the other tetrachloro-1,4-
benzoquinone (TCQ) [36]. More recently, Coskun
reported a reaction where the in situ formed 2-substi-
tuted-1,2,3,4-tetrahydroquinazolines were oxidized to
quinazolin-1-oxides [37].
The quinazoline ring is a frequently encountered moi-
ety in organic syntheses as well as in medicinal chemistry
[1–10]. Many alkaloids containing a quinazoline skeleton
in the molecule exhibit anticonvulsant, antibacterial, anti-
diabetic, and anticancer activities [6,11–14]. A number of
methods for the synthesis of quinazolines are known [15–
19]. We found five basic types of synthetic strategies for
the synthesis of 2-substitued quinazolines: (1) three-step
reaction from aryl azides to form 2-alkylquinazolines
[20], (2) reaction of amidines with cyano- or nitro-acti-
vated o-fluorobenzaldehydes [21], (3) condensation of o-
phenyl oxime of 2-aminoacetophenone with aldehydes or
ketones by irradiation with microwaves to form 4-methyl-
quinazolines [22], (4) reaction of 2-aminobenzaldehyde
with an acyl halide and by heating the obtained amide in
a sealed tube with saturated alcoholic ammonia [19,23–
26], and then dehydrogenation with mercuric EDTA
complex or aromatization with alkaline potassium ferri-
cyanide [27,28], (5) condensation of 1,3-diamines 1 with
aromatic aldehydes 2 to form 2-aryl-1,2,3,4-tetrahydro-
quinazolines 3, and then oxidation of 3 to form the 2-aryl
substituted quinazolines 4 (Scheme 1).
No one-pot reaction to synthesize 2-arylquinazolines
was reported. The methods described above to synthesize
the 2-arylquinazolines either require multistep prepara-
tions of special reagents/reactants, or suffer severe limita-
tions such as tedious experimental procedure and poor
yields. Here we report the first one-pot synthesis of 2-aryl
substituted quinazolines, from condensation of 1,3-dia-
mines 1 with aryl aldehydes 2 to form 2-aryl-1,2,3,4-tetra-
hydroquinazolines 3, and oxidation of 3 to form the 2-aryl
substituted quinazolines 4, using MnO2 as the oxidant.
The fifth synthetic strategy involves two steps: con-
densation and oxidation. The condensation products, 2-
aryl-1,2,3,4-tetrahydroquinazolines, have been prepared
in solvent-free [29] and a number of solvents, including
benzene or xylene, methanol or ethanol/acetic acid mix-
RESULTS AND DISCUSSION
The condensation of 2-aminobenzylamine and benzal-
dehyde was selected as the model reaction. Among the
C
V
2010 HeteroCorporation

September 2010
A Convenient One-Pot Procedure for the Synthesis of 2-Aryl
Quinazolines Using Active MnO2 as Oxidant
1241
Scheme 1
Table 1
The solvent effect on the condensation reaction.
that the synthesis of quinazolines might proceed in one
pot.
We then investigated the one-pot reactions of 2-ami-
nobenzylamines and benzaldehydes to synthesize 2-aryl-
qunazolines without isolating the tetrahydroquinazoline
intermediate. First, the reaction of 2-aminobenzylamine
with benzaldehyde gave tetrahydroquinazoline in CHCl3
at room temperature. After TLC indicated the reaction
was completed, we added 4.0 mol equivalents of MnO2.
After refluxing for 12 h, the corresponding quinazoline
was isolated in 70% yield. To explore the generality and
scope of this one-pot reaction, we synthesized 2-arylqui-
nazolines from a variety of 2-aminobenzylamines and
aryl aldehydes (Table 4).
Entry
Solvent
Time (h)
Yielda (%)
1
2
3
4
5
6
H2O
CHCl3
THF
CH3OH
CH3CN
CH2Cl2
4
10
16
17
16
18
85
84
66
73
74
63
a Isolated yield based on 2-aminobenzylamine.
solvents we screened, we found CHCl3 or H2O was the
best solvent to give the product in high yield (Table 1,
entries 1 and 2). Other solvents such as THF, CH3OH,
CH3CN, and CH2Cl2 gave lower yields (entries 3–6).
This is consistent with the findings of Gawinecki et al.
[38].
A variety of substituents are tolerated on both 2-ami-
nobenzylamines and benzaldehydes. For the 2-amino-
benzylamines, ortho F or CF3 substituents slowed the
reaction, probably due to the electronic and steric effect
in the first step (entries 15–18). For benzaldehydes, the
electron-withdrawing substituents speeded the reaction.
Overall the reaction gave 2-arylquinazolines in yields
from 26 to 75%.
Several oxidants were evaluated for the transforma-
tion of tetrahydroquinazoline 3 to quinazoline 4 in
CHCl3 (Table 2). Among the oxidants we used, only
DDQ and MnO2 were effective for the transformation
from the tetrahydroquinazoline to the quinazoline (Ta-
ble 2, entries 4–5).
CONCLUSION
We then evaluated the solvent effects on the oxidation
of the tetrahydroquinazoline to the quinazoline. The
reaction did not proceed in water or in CH3COOH (Ta-
ble 3, Entries 1 and 2). Moderate yields were obtained
in CH3OH, C2H5OH, CH2Cl2, CH3CN, Dioxane, DMF,
and THF (Entries 3–9). The best yield was obtained in
CHCl3 (Entry 10). Because both condensation and oxi-
dation reactions proceed well in CHCl3, we envisioned
In summary, We have developed an one-pot method
to synthesize a variety of 2-arylquinazoline derivatives,
from the condensation of 1,3-diamines and aryl alde-
hydes to form 2-aryl-1,2,3,4-tetrahydroquinazolines and
subsequent oxidation of tetrahydroquinazolines with
Table 3
The solvent effect on the oxidation of 2-phenyltetrahydroquinazolin.
Entry
Solvent
Time1 (h)
Time2 (h)
Yielda (%)
Table 2
1
2
H2O
CH3COOH
CH3OH
C2H5OH
CH2Cl2
CH3CN
Dioxane
DMF
5
4
24
12
12
12
12
12
12
8
–
–
The effect of oxidants on the oxidation of 2-
phenyltetrahydroquinazoline to quinazoline.
3
24
24
36
16
15
16
16
10
37
35
30
51
54
54
68
70
4
5
Entry
Oxidant
Time (h)
Yielda (%)
1
2
3
4
5
NBS
Br2
36
36
36
36
36
0
0
6
7
Pb(OAC)4
DDQ
MnO2
0
65
70
8
9
10
THF
CHCl3
12
12
a Isolated yield.
a Isolated yield.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Y.-Y. Peng, Y. Zeng, G. Qiu, L. Cai, and V. W. Pike
Vol 47
Table 4
One-pot synthesis of 2-arylquinazolines.
Entry
Product
Time1 (h)
10
Time2 (h)
Yielda (%)
1
12
70
2
6
12
72
3
4
5
5
5
5
12
12
12
62
52
66
6
7
5
7
12
12
75
50
8
8
12
66
9
10
10
12
12
56
48
10
11
12
9
12
12
40
30
10
(Continued)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2010
A Convenient One-Pot Procedure for the Synthesis of 2-Aryl
Quinazolines Using Active MnO2 as Oxidant
1243
Table 4
(Continued)
Entry
13
Product
Time1 (h)
10
Time2 (h)
12
Yielda (%)
50
14
15
4
13
14
48
42
20
16
20
14
40
17
18
20
20
12
20
48
26
a Isolated yield based on 2-aminobenzylamines.
MnO2 was added and refluxed. After the reaction was com-
pleted, the organic material was extracted with ethyl acetate.
The organic layer was dried over Na2SO4, and the solvents
were removed. The residue was purified by flash chromatogra-
phy on silica gel column, using petroleum/ethyl acetate as elu-
ate to give products.
MnO2 in moderate to high yield. This method provided
quick access to different quinazolines.
EXPERIMENTAL
Melting points were determined on an Electrothermal 9100
capillary melting point apparatus. 1H NMR spectra were
recorded on a Bruker AV400 (400 MHz) spectrometer, and
chemical shifts (d) are reported in parts per million relative to
tetramethylsilane. 13C NMR spectra were recorded on a Bruker
AV400 spectrometer, and chemical shifts are reported in parts
per million relative to solvent resonance as the internal stand-
ard (CDCl3, d 77.16). IR spectra were recorded as solid in pel-
lets on a Perkin-Elmer FTIR 683 spectrometer. Mass spectra
were obtained with a TRIO 2 (electronic ionization 70 eV)
spectrometer and a Perkin-Elmer Claruss 500 mass spectrome-
ter (electronic ionization 20 eV).
General procedure for the synthesis of 2-aryl-
tetrahydroquinazolines. A mixture of 2-aminobenzylamine
(1.1 mmol), aryl aldehyde (1.0 mmol), and 10 mL of solvent
were stirred at room temperature. The reaction was followed
by TLC. When the reaction was completed, 4 mmol of active
2-Phenylquinazoline.37 This compound was obtained as yel-
low solid, mp 91–92ꢁC; 1H NMR (dimethyl sulfoxide d6): d
7.53–7.56 (m, 3H, ArAH), 7.69–7.73 (m, 1H, ArAH), 8.00–
8.04 (m, 2H, ArAH), 8.13 (d, J ¼ 8.0 Hz, 1H), 8.54–8.56 (m,
2H, ArAH), 9.67 (s, 1H); 13C NMR (deuteriochloroform): d
123.6, 127.1, 127.3, 128.6, 128.7, 130.6, 134.1, 138.0, 150.8,
160.5, 161.1.
2-(4-Nitro-phenyl)quinazoline.33 This
compound
was
obtained as yellow solid, mp 197–198ꢁC; 1H NMR (deuterio-
chloroform): d 7.70 (t, 1H, J ¼ 7.2 Hz), 7.89–7.96 (m, 1H),
8.38 (d, 2H, J ¼ 8.8 Hz), 8.83 (d, 2H, J ¼ 8.8 Hz), 9.50 (s,
1H); 13C NMR (deuteriochloroform): d 123.8, 123.9, 127.2,
128.3, 128.9, 129.4, 134.6, 143.8, 149.2, 150.6, 158.8, 160.7.
2-(3-Nitro-phenyl)quinazoline.33 This
compound
was
obtained as yellow solid, mp 194–195ꢁC; 1H NMR (deuterio-
chloroform): d 7.68–7.73 (m, 2H), 7.98 (t, J ¼ 8.0 Hz, 2H),
8.14 (d, J ¼ 8.0 Hz, 1H), 8.34 (d, J ¼ 8.0 Hz, 1H), 8.98 (d, J
Journal of Heterocyclic Chemistry
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Y.-Y. Peng, Y. Zeng, G. Qiu, L. Cai, and V. W. Pike
Vol 47
¼ 7.6 Hz, 1H), 9.51 (s, 2H); 13C NMR (deuteriochloroform):
d 123.6, 123.9, 125.1, 127.3, 128.1, 128.8, 129.6, 134.2, 134.6,
139.9, 150.6, 158.7, 160.8.
2-(Benzo[1,3]dioxol-5-yl)quinazoline. This compound was
obtained as yellow solid, mp 123–125ꢁC; IR (potassium bro-
mide): 2921, 2850, 1618, 1584, 1568, 1502, 1460, 1256, 1099,
2-(2-Nitro-phenyl)quinazoline.37 This
compound
was
1
1039, 793 cmꢂ1. H NMR (deuteriochloroform): d 6.06 (s, 2H,
obtained as yellow solid, mp 91–92ꢁC; 1H NMR (deuterio-
chloroform): d 7.68–7.73 (m, 2H), 7.98 (t, J ¼ 8.0 Hz, 2H),
8.14 (d, J ¼ 8.0 Hz, 1H), 8.34 (d, J ¼ 8.0 Hz, 1H), 8.98 (d, J
¼ 7.6 Hz, 1H), 9.51 (s, 2H); 13C NMR (deuteriochloroform):
d 123.6, 124.0, 125.1, 127.2, 128.1, 128.8, 129.6, 134.2, 134.6,
139.8, 148.9, 150.6, 158.7, 160.8.
OCH2O), 6.97 (d, 1H, J ¼ 8.4 Hz, ArAH), 7.59 (s, 1H,
ArAH), 7.91–7.89 (m, 2H, ArAH), 8.04–8.03 (m, 1H, ArAH),
8.20 (s, 1H, ArAH), 8.23 (d, 1H, J ¼ 7.0 Hz, ArAH), 9.41 (s,
1H, ArAH); 13C NMR (deuteriochloroform): d 29.7, 46.5,
69.4, 101.2, 107.1, 108.3, 115.0, 118.2, 120.1, 121.3, 126.2,
127.3, 135.8, 143.7, 147.7. HRMS calcd. for C15H10N2O2:
250.0742, found: 250.0740.
2-(4-Hydroxyl-phenyl)quinazoline. This compound was
obtained as yellow solid, mp 210–212ꢁC; IR (potassium bro-
mide): 3168, 1670, 1606, 1555, 1457, 1405, 1385, 1240, 1165,
2-(4-Chloro-phenyl)quinazoline.33 This compound was
obtained as yellow solid, mp 116–117ꢁC; 1H NMR (deuterio-
chloroform): d 7.49 (d, J ¼ 7.6 Hz, 2H), 7.62–7.65 (m, 1H,
ArAH), 7.90–7.95 (m, 2H, ArAH), 8.07 (d, J ¼ 8.4 Hz, 1H),
8.58 (d, J ¼ 8.8 Hz, 2H, ArAH), 9.46 (s, 1H); 13C NMR (deu-
teriochloroform): d 123.6, 127.2, 127.5, 128.6, 128.9, 129.9,
134.3, 136.5, 136.9, 150.7, 160.1, 160.6.
799 cmꢂ1
.
1H NMR (deuteriochloroform): d 6.92 (d, J ¼ 8.4
Hz, 3H), 7.64–7.69 (m, 1H), 7.97 (d, J ¼ 3.2 Hz, 2H), 8.09
(d, J ¼ 8.0 Hz, 1H), 8.41 (d, J ¼ 8.8 Hz, 2H), 9.61 (s, 1H);
13C NMR (deuteriochloroform): d 115.9, 116.3, 123.4, 127.4,
128.1, 128.2, 128.9, 130.4, 135.1, 150.4, 160.5, 161.5. HRMS
calcd. for C14H10N2O: 222.0793, found: 222.0795.
2-(4-Bromo-phenyl)-quinazoline. This
obtained as yellow solid, mp 131–132ꢁC; IR (potassium bro-
mide): 2925, 1693, 1618, 1582, 1546, 1405, 1369, 1067 cmꢂ1
compound
was
.
1H NMR (deuteriochloroform): d 7.62–7.68 (m, 3H, ArAH),
7.91–7.95 (m, 2H), 8.08 (d, 1H, J ¼ 8.4 Hz), 8.51 (d, 2H, J ¼
8.4 Hz), 9.46 (s, 1H); 13C NMR (deuteriochloroform): d 123.7,
125.5, 127.2, 127.6, 128.6, 130.2, 131.8, 134.4, 136.9, 150.7,
160.1, 160.6. HRMS calcd. for C14H9BrN2: 283.9949, found:
283.9951.
2-(6-Bromo-pyridin-3-yl)-quinazoline. This compound was
obtained as black solid, mp 158–160ꢁC; IR (potassium bro-
mide): 3061, 2924, 1619, 1572, 1448, 1404, 1088, 734 cmꢂ1
.
1H NMR (deuteriochloroform): d 7.61–7.69 (m, 2H, ArAH),
7.92–7.96 (m, 2H), 8.07 (d, J ¼ 8.8 Hz, 1H), 8.73 (dd, 1H, J
¼ 1.6, 8.4Hz), 9.45 (s, 1H), 9.55 (d, J ¼ 1.6 Hz, 1H); 13C
NMR (deuteriochloroform): d 123.9, 127.2, 127.9, 128.0,
128.7, 133.0, 134.6, 138.2, 144.2, 150.6, 150.7, 158.3, 160.7.
HRMS calcd. for C13H8BrN3: 284.9902, found: 284.9905.
2-(2-Furyl)quinazoline.37 This compound was obtained as
2-(4-Trifluoromethyl-phenyl)quinazoline. This
compound
was obtained as brown-yellow solid, mp 120–122ꢁC; IR (po-
tassium bromide): 2925, 2854, 1621, 1553, 1326, 1163, 1116
cmꢂ1
.
1H NMR (deuteriochloroform): d 7.68 (t, J ¼ 7.6 Hz,
1
black solid, mp 131–132ꢁC; H NMR (deuteriochloroform): d
1H), 7.78 (d, J ¼ 8.4 Hz, 2H), 7.94–7.98 (m, 2H, ArAH),
8.12 (d, J ¼ 8.4 Hz, 1H), 8.75 (d, J ¼ 8.4 Hz, 2H), 9.51 (s,
1H); 13C NMR (deuteriochloroform): d 122.7 (q, J ¼ 262.0
Hz), 123.7, 123.9, 127.2, 128.3, 128.9, 129.4, 134.6, 143.8,
149.2, 150.6, 158.8, 160.7. HRMS calcd. for C15H9F3N2:
274.0718, found: 274.0720.
6.63 (dd, J ¼ 2.0, 3.6 Hz, 1H), 7.46 (d, J ¼ 3.2 Hz, 1H),
7.59–7.63 (m, 1H), 7.70 (d, J ¼ 0.8 Hz, 1H), 7.89–7.93 (m,
2H), 8.09 (d, J ¼ 9.2 Hz, 1H), 9.39 (s, 1H); 13C NMR (deuter-
iochloroform): d 112.4, 114.1, 123.4, 127.3, 128.4, 134.6,
145.4, 150.4, 152.5, 154.1, 160.8.
2-(4-Acetamido-phenyl)quinazoline. This compound was
obtained as brown-yellow solid, mp 136–139ꢁC; IR (potassium
bromide): 3445, 3259, 2925, 1697, 1602, 1532, 1408, 1312,
2-Phenyl-5-flouroquinazoline. This compound was obtained
as yellow solid, mp 111–113ꢁC; IR (potassium bromide):
3058, 2925, 1635, 1582, 1555, 1465, 1398, 1240, 790, 699
cmꢂ1
.
1H NMR (deuteriochloroform): d 7.22 (t, 1H, J ¼ 8.4
1
799 cmꢂ1. H NMR (deuteriochloroform): d 2.23 (s, 3H), 7.39
Hz), 7.53–7.56 (m, 3H, ArAH), 7.83–7.90 (m, 2H, ArAH),
8.62–8.63 (m, 2H, ArAH), 9.74 (s, 1H); 13C NMR (deuterio-
chloroform): d 110.9 (d, J ¼ 19.0 Hz), 114.1, 124.6 (d, J ¼
4.0 Hz), 128.7 (d, J ¼ 6.0 Hz), 131.0, 134.1 (d, J ¼ 10.0 Hz),
137.6, 152.0, 154.9 (d, J ¼ 3.0 Hz), 157.0 (d, J ¼ 257.0 Hz),
161.2. HRMS calcd. for C14H9FN2: 224.0750, found:
224.0752.
(br s, 1H), 7.60 (t, J ¼ 7.6 Hz, 1H), 7.68 (d, J ¼ 8.4 Hz, 2H),
7.88–7.93 (m, 2H), 8.06 (d, J ¼ 8.4 Hz, 1H), 8.59 (d, J ¼ 8.4
Hz, 2H), 9.44 (s, 1H); 13C NMR (deuteriochloroform): d 24.8,
119.4, 123.5, 127.1, 128.5, 129.5, 131.1, 133.9, 134.1, 140.2,
150.8, 160.5, 168.4. HRMS calcd. for C16H13N3O: 263.1059,
found: 263.1057.
2-(4-Methyl-phenyl)quinazoline.36 This compound was
obtained as yellow solid, mp 99–101ꢁC; IR (potassium bro-
mide): 3027, 2922, 2854, 1620, 1610, 1589, 1552, 1402, 1380,
2-(4-Acetamido-phenyl)-5-flouroquinazoline. This
com-
pound was obtained as yellow solid, mp 207–208ꢁC; IR (po-
tassium bromide): 3536, 3283, 3126, 2926, 1633, 1656, 1580,
1
797, 726 cmꢂ1. H NMR (deuteriochloroform): d 2.44 (s, 3H),
1
1556, 1463, 1397, 1376, 1347, 1237, 1089, 822. H NMR (di-
7.33 (d, J ¼ 7.2 Hz, 2H), 7.57–7.60 (m, 1H), 7.87–7.91 (m,
2H), 8.05 (d, J ¼ 8.8 Hz, 1H), 8.50 (d, J ¼ 7.2 Hz), 9.44 (d, J
¼ 0.8 Hz); 13C NMR (deuteriochloroform): d 21.5, 123.5,
127.1, 128.6, 129.4, 134.1, 135.3, 140.9, 150.8, 160.5.
methyl sulfoxide d6): d 2.10 (s, 3H), 7.49 (t, J ¼ 8.8 Hz, 1H),
7.77 (d, J ¼ 8.4 Hz, 2H), 7.85 (d, J ¼ 8.4 Hz, 1H), 7.97–8.03
(m, 1H), 8.48 (d, J ¼ 8.8 Hz, 2H), 9.78 (s, 1H), 10.23 (br s,
1H); 13C NMR (deuteriochloroform): d 24.5, 111.7 (d, J ¼
18.0 Hz), 113.9 (d, J ¼ 16.0 Hz), 119.1 (d, J ¼ 8.0 Hz), 124.6
(d, J ¼ 4.0 Hz), 129.6, 131.9, 135.7 (d, J ¼ 10.0Hz), 142.6,
151.2, 155.6, 156.8 (d, J ¼ 246 Hz), 160.7 169.2. HRMS
calcd. for C16H12FN3O: 281.0964, found: 281.0967.
2-(4-Methoxyl-phenyl)quinazoline.36 This compound was
obtained as yellow solid, mp 85–86ꢁC; 1H NMR (deuterio-
chloroform): d 3.89 (s, 3H), 7.03 (d, J ¼ 8.8 Hz, 2H), 7.56 (t,
J ¼ 7.6 Hz, 1H), 7.82–7.89 (m, 2H, ArAH), 8.02 (d, J ¼ 8.4
Hz, 1H), 8.56 (d, J ¼ 8.8 Hz, 2H), 9.41(s, 1H); 13C NMR
(deuteriochloroform):
d
55.4, 113.9, 123.3, 126.8, 127.1,
2-Phenyl-8-trifluoromethylquinazoline. This compound was
obtained as yellow solid, mp 94–96ꢁC; IR (potassium
128.4, 130.2, 130.7, 134.0, 150.8, 160.4, 160.8, 161.8.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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A Convenient One-Pot Procedure for the Synthesis of 2-Aryl
Quinazolines Using Active MnO2 as Oxidant
1245
[11] Michael, J. P. Nat Prod Rep 2003, 20, 476.
[12] Michael, J. P. Nat Prod Rep 2002, 19, 742.
[13] Michael, J. P. Nat Prod Rep 1999, 16, 697.
bromide): 3070, 1621, 1590, 1568, 1468, 1475, 1410, 1343,
1281, 1159, 1078, 773 cmꢂ1 1H NMR (dimethyl sulfoxide
.
d6): d 7.54 (d, J ¼ 4.0 Hz, 3H), 7.66 (t, J ¼ 7.6 Hz, 1H), 8.10
(d, J ¼ 7.6 Hz, 1H), 8.23 (d, J ¼ 7.2 Hz, 1H), 8.68 (d, J ¼
4.0 Hz, 2H), 9.52 (s, 1H); 13C NMR (dimethyl sulfoxide d6): d
123.7(q, J ¼ 242.2 Hz), 125.8, 128.7, 129.0, 131.3, 131.4,
132.1, 132.2, 137.4, 147.7, 160.7, 161.4. HRMS calcd. for
C15H9F3N2: 274.0718, found: 274.0721.
2-(4-Acetamido-phenyl)-8-trifluoromethylquinazoline. This
compound was obtained as yellow solid, mp 166–168ꢁC; IR
(potassium bromide): 3265, 3121, 2926, 2853, 1675, 1601,
1596, 1471, 1327, 1286, 1139, 833, 775 cmꢂ1 1H NMR (di-
.
methyl sulfoxide d6): d 2.23 (s, 3H), 7.56–7.72 (m, 3H), 7.84
(d, J ¼ 7.6 Hz, 1H), 8.08 (d, J ¼ 8.0 Hz, 1H), 8.22 (d, J ¼
6.8 Hz, 1H), 8.64 (d, J ¼ 8.0 Hz, 1H), 9.49 (s, 1H). 13C NMR
(dimethyl sulfoxide d6): d 24.3, 113.0, 113.2, 116.3, 121.7 (q,
J ¼ 248.3), 124.9, 127.1, 129.1, 129.8, 131.1, 131.8, 136.7,
138.5, 144.3, 169.5. HRMS calcd. for C17H12F3N3O:
331.09325, found: 331.09367.
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Acknowledgments. We are grateful to the support from the
National Science Foundation of China (No. 20462003,
20862009, and 20962010) and the National Science Foundation
of Jiangxi province (No. 2008GQH0026).
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet