Synthesis of 2-dihydrooxadiazolinyl chromones

Article abstract of DOI:10.1002/jccs.200300127

Reactions of the substituted 2-formyl chromones with aroylhydrazines gave corresponding 2-(aroylhydrazonomethylidyne) chromones. Then 2-(3′-acetyl- 5′-aryl-2′,3′-dihydro-1′,3′,4′-oxadiazol- 2′-yl) chromones were prepared by these 2-(aroylhydrazonomethylidyne) chromones under refluxing with Ac₂O. All target compounds were characterized through elemental analysis and IR, ¹H NMR, MS.

Full text of DOI:10.1002/jccs.200300127

Journal of the Chinese Chemical Society, 2003, 50, 903-908
903
Synthesis of 2-Dihydrooxadiazolinyl Chromones
Ling-hua Caoa,b* (
) and Peng-yuan Cuia (
)
aDepartment of Chemistry, Xinjiang University, Urumqi Xinjiang, 830046, P. R. China
bState Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, P. R. China
Reactions of the substituted 2-formyl chromones with aroylhydrazines gave corresponding 2-(aroylhy-
drazonomethylidyne) chromones. Then 2-(3¢-acetyl-5¢-aryl-2¢,3¢-dihydro-1¢,3¢,4¢-oxadiazol-2¢-yl) chromo-
nes were prepared by these 2-(aroylhydrazonomethylidyne) chromones under refluxing with Ac2O. All target
compounds were characterized through elemental analysis and IR, 1H NMR, MS.
Keywords: Oxadiazoline; Chromone; Synthesis.
INTRODUCTION
There are a lot of compounds which include a chro-
responding 2-formyl chromones were formed.11 Reactions of
the substituted 2-formyl chromones with aroylhydrazines
gave corresponding 2-(aroylhydrazonomethylidyne) chro-
mones (2~21). Then 2-(3¢-acetyl-5¢-aryl-2¢,3¢-dihydro-1¢,3¢,4¢-
oxadiazol-2¢-yl) chromones were (22~41) prepared by these
2-(aroylhydrazonomethylidyne) chromones refluxing under
Ac2O. We synthesized the title compounds according to the
following route (Scheme I, Table 1).
mone nucleus in nature. They have been interesting because
of their special framework and wide biomedical activities,
e.g., antimicrobial, antiallergic, anti-inflammatory, anti-
tumor, anti-spastic, reducing bloodsugar and fats in blood,1-7
and so on. Heterocyclic compounds, such as 1,3,4-oxadi-
azole, also have versatile and significant biological activities
as fungicides, antimicrobes, insecticides, as well as anti-
convulsives.8,9 The derivatives of 1,3,4-oxadiazole which are
linked with quinoline10 and theophylline11 have been re-
ported. Acylhydrazines prove to be suitable trapping agents
for the isolation of oxo compounds, and acylhydrazones due
to their biological activities can be regarded as potential
pharmacons.12 A series of investigations on combining these
components often exhibited some novel biological activities
in addition to the above mentioned compounds. In view of
this, the synthesis of 2-heterocyclic linked chromones at-
tracted our interest.
RESULTS AND DISCUSSION
2-Formyl chromones were prepared from 2-methyl
Table 1. The Target Compounds
Compd.
R
Ar
2, 22
3, 23
4, 24
5, 25
6, 26
7, 27
8, 28
9, 29
10, 30
11, 31
12, 32
13, 33
14, 34
15, 35
16, 36
17, 37
18, 38
19, 39
20, 40
21, 41
H
H
H
H
H
CH3
CH3
CH3
CH3
CH3
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
C6H5
p-Cl-C6H4
o-Cl-C6H4
p-CH3O-C6H4
p-NO2-C6H4
C6H5
p-Cl-C6H4
o-Cl-C6H4
p-CH3O-C6H4
p-NO2-C6H4
C6H5
p-Cl-C6H4
o-Cl-C6H4
p-CH3O-C6H4
p-NO2-C6H4
C6H5
p-Cl-C6H4
o-Cl-C6H4
p-CH3O-C6H4
p-NO2-C6H4
In this paper we describe the synthesis and physical
characterization of new 2-heterocyclic linked chromones
22~41. And all the new compounds were characterized by el-
emental analysis and IR, 1H NMR, MS spectral data. Biologi-
cal activities are being tested.
The 2-formyl chromones were prepared from 2-acetyl
phenol. 2-acetyl phenol could condense with ethyl acetate
under sodium catalyzation, so 2-acetylacetyl phenol could be
prepared though their sodium salt. Then substituted 2-methyl
chromones were formed by 2-acetylacetyl phenol under cata-
lytic amounts of concentrated hydrochloric acid and HOAc.6
The substituted 2-methyl chromones reacted with p-nitro-
sodimethylaniline, which gave corresponding nitrones.
Nitrones were treated with dilute sulphuric acid, then the cor-
Br

904 J. Chin. Chem. Soc., Vol. 50, No. 4, 2003
Cao and Cui
Scheme I
O
O
CH
3
HOAc
reflux
R
OH
R
OH
1) Na, CH CO Et
3
2
2) dil. HOAc
COCH COCH
2
R
COCH
3
3
O
O
CHO
1) p-(CH ) NC H NO/ EtONa
ArCONHNH
3 2
6 4
2
2) dil. H SO
2
4
R
1
COCH
N N
3
O
O
CH=NNHCOAr
O
Ar
Ac O
2
O
reflux
R
R
O
22~41
2~21
chromones. In other articles the preparation of 2-formyl
chromones had two methods. One method was using sele-
nium dioxide, 2-methyl at chromone nucleus to carbonyl
could be oxidized selectively.12 The other was an indirect
conversion with two steps reaction. The first step involved
conversion of 2-methyl chromones into corresponding ni-
trones, which on treatment with dilute sulphuric acid, in the
second step gave 2-formyl chromones. Because with the first
method there must be separation by chromatography and
with a lot of by-products, this was inconvenient. We selected
the second method, but it wasn’t reported in detail. We made
certain of the minimal quantity of solvent and the reaction
time, and improved the yield.
The IR spectra of compounds 22~41 clearly differ from
the spectra of corresponding 2-(aroylhydrazomethylidyne)
chromones 2~21. The compounds 2~21 exhibited a wide
peak at 3280-3090 cm-1 (NH). But for the compounds 22~41,
the peaks in these bands were devoid. At the same time, the
IR spectra of compounds 22~41 shows strong absorption at
1640-1635 cm-1 (pyrone C=O) and 1685-1680 cm-1 (COCH3),
and exhibited strong absorption at 1600-1598 cm-1 (C=N).
The 1H NMR spectra of compounds 22~41 are in per-
fect agreement with the suggested structures of target com-
pounds. The 1H NMR spectra of 22~41, as a representative,
exhibited signals at d 2.3 (COCH3, s), d 6.8 (CH), d 7.3 (H-3,
s). Then chromone proton H-5 displayed as a double peak at d
8.1 (coupling with H-7, 4J ~ 2.4 Hz), and H-7 showed d ´ d
peaks because this proton coupled with H-5 and H-8, respec-
tively (4J ~ 2.4 Hz, 3J ~ 8 Hz).
2-Formyl chromones could react with aroylhydrazine
easily, then give corresponding aroylhydrazonomethylidyne
chromones. However, 4-carbonyl at a chromone nucleus re-
acted with aroylhydrazine, too, under certain conditions. But
2-formyl at a chromone nucleus is more active than 4-car-
bonyl at a chromone. So we controlled the condition of the re-
action so that aroylhydrazine reacted with 2-formyl at the
chromone only and didn’t react with 4-carbonyl at the chro-
mone. We adopted the room temperature and equimolecular
quantities material ratio. Under glacial acetic acid catalyza-
tion, our expected results could separate out rapidly as pre-
cipitation. And we found that the yield was higher when
aroylhydrazine linked electron-attracting radicals. This
could be the character of radical effect on the nucleophilic
character of reactant and the electron density of the product.
When the ring closure of 2-(aroylhydrazonomethyl-
idyne) chromones was taken through the reacting with acetic
anhydride, the dosage of acetic anhydride was more than oth-
ers. Because the solubility of this kind of 2-(aroylhydrazo-
methylidyne) chromones was low.
In EI-MS spectra, most of the compounds 22~41 have a
molecular ion peak, but their abundance is less. This indi-
cated compounds 22~41 were not very stable conjugate mol-
ecules. They also showed RDA fragmentation in which the
flavone compounds were common. The compounds 22~41
were shown to lose CH2=C=O at first, then formed 2-
(1¢,3¢,4¢-oxadiazole-2¢-yl) chromones. Then they cleaved
like oxadiazole type compounds. The cleaving of compounds
36 is in Scheme II. We confirmed the structure of those com-
pounds by elemental analyses.
EXPERIMENTAL
General Method
Melting points were taken on a Yanaco MP-S3 micro
melting point apparatus. The IR spectra were recorded in

Synthesis of 2-Dihydrooxadiazolinyl Chromones
J. Chin. Chem. Soc., Vol. 50, No. 4, 2003 905
Scheme II
COCH
3
H
N N
N N
- CH CO
2
O
O
O
O
NO
2
NO
Cl
Cl
2
O
O
m/z 413
m/z 371
RDA
+
O
Cl
+
O
H
N N
O
O
m/z 180
O
H
O
Cl
+
NO
2
O
m/z 192
m/z 221
Cl
CO
m/z 154
+
OC
+
O
+
NO
2
CO
Cl
Cl
m/z 150
m/z 126
m/z 152
+
+
CO
m/z 105
C H
6
5
Cl
m/z 98
m/z 77
1
KBr pellets on a Bruker FT-IR Equinox apparatus. The H
NMR spectra were recorded on an INOVA-400 (using TMS
as internal standard, d6-DMSO as solvent). MS were re-
corded on a HP 5890. Elemental analyses were performed on
a Yanaco CHN Corder MT-3 analyzer. The TLC was per-
formed by GF-254 and 0.5% CMC. Detection made use of
UV light; the mobile phase was petroleum ether and ethyl ac-
etate (1:1).
2-acetylacetyl phenol (0.01 mol) was boiled for 2 min
with acetic acid (10 mL), then a few drops of concentrated
hydrochloric acid were added and refluxed for 15 min. After
cooling, the mixture was poured into ice-water. The crude
product was filtered off as precipitate and recrystallized from
ethanol.
Preparation of 6-substituted 2-formyl chromones 111
A solution of 6-substituted 2-methyl chromones (4
mmol) and p-nitrosodimethylaniline (12 mmol) in 10 mL eth-
anol (the least quantity) was added to an ethanolic solution of
sodium ethoxide (4 mmol). After stirring, the red nitrones ap-
peared, and were filtered off and recrystallized from n-bu-
tanol.
Preparation of 6-substituted 2-methyl chromones6
Under nitrogen atmosphere, the mixture of 0.2 mol
2-acetyl phenol and 165 mL ethyl acetate (free ethanol) was
added dropwise into 8 g powdered sodium; when the vigor-
ous reaction had ceased, the mixture was heated in an oil bath
for an hour. The product was shaken with 150 g crushed ice.
And the yellow sodium salt was filtered, washed with ice-
cold water, then ether, and decomposed by treatment with
32% acetic acid. The crude product was filtered off as precip-
itate. 2-acetylacetyl phenol was recrystallized from ethanol.
A mixture of nitrones (0.5 g) and 10 M sulphuric acid (8
mL) was shaken at room temperature for 15 min, and water
(25 mL) was added to it. The crude products that were depos-
ited were filtered off, washed with water and recrystallized
from an appropriate solvent.

906 J. Chin. Chem. Soc., Vol. 50, No. 4, 2003
Cao and Cui
Preparation of 2-(Aroylhydrazonomethylidyne)
Chromones 2~21
OCH3), 2.38 (s, 3H, COCH3). IR (KBr) nmax 1678 (s, C=O),
1645 (s, pyrone C=O), 1598 (s, C=N), 1278 (m, C-O-C). m/z
(%): 364 (M+, 11), 322 (16), 188 (50), 177 (12), 146 (30), 135
(100), 117 (32), 120 (15), 105 (17), 92 (5), 77 (40).
A solution of 6-substituted 2-formyl chromones 1 (0.5
g) in ethanol (15 mL) was added to a solution of an equimolar
amount of aroylhydrazines in ethanol (5 mL) and 2 mL acetic
acid as catalyst. After stirring for 15 min, precipitation ap-
peared. Through TLC detection, the reaction was completed
in 2 hours. The crude product was filtered and was recrys-
tallized from DMF.
26: Yield: 80%, m.p. 176-177 °C, C19H13N3O6, Calcd.:
C, 60.16; H, 3.45; N, 11.08; Anal.: C, 59.60; H, 3.38; N,
11.49. d : 8.40-8.38 (m, 4H, Ar-H), 8.14-8.13 (m, 3H, Ar-H),
H
7.97 (d ´ d, 1H, H-7, 3J = 8.8 Hz, 4J = 2.6 Hz), 7.12 (s, 1H,
H-3), 6.72 (s, 1H, oxadiazole-CH), 2.39 (s, 3H, COCH3). IR
(KBr) n 1680 (s, C=O), 1640 (s, pyrone C=O), 1590 (s,
max
Preparation of 2-(3¢-acetyl-5¢-aryl-2¢,3¢-dihydro-1¢,3¢,4¢-
oxadiazol-2¢-yl) Chromones 22~41
C=N), 1521 (m, -NO2), 1347 (m, NO2), 1273 (m, C-O-C). m/z
(%): 379 (M+, 9), 337 (15), 192 (6), 150 (100), 120 (19), 105
(28), 92 (5), 77 (20).
A mixture of aroylhydrazonomethylidyne chromone
2~21 (0.2 g) and acetic anhydride (50 mL) was refluxed for 3
h. After the reaction mixture was cooled, it was poured into
ice-cold water. After excessive acetic anhydride was hydro-
lyzed, the solid was separated. It was recrystallized from eth-
anol.
27: Yield: 70%, m.p. 203-204 °C, C20H16N2O4, Calcd.:
C, 68.96; H, 4.63; N, 8.04; Anal.: C, 69.11; H, 4.59; N, 8.08.
d : 7.89-7.84 (m, 3H, 5-H, Ar-H), 7.64-7.51 (m, 5H, 7-H,
H
8-H, Ar-H), 7.14 (s, 1H, H-3), 6.73 (s, 1H, oxadiazole-CH),
2.42 (s, 3H, COCH3), 2.32 (s, 3H, CH3); IR (KBr) n
max
22: Yield: 71%, m.p. 150-151 °C, C19H14N2O4, Calcd.:
C, 68.26; H, 4.22; N, 8.38. Anal.: C, 68.41; H, 4.30; N, 8.43.
1690-1664 (s, w, C=O & pyrone C=O), 1598 (m, C=N), 1286
(m, C-O-C). m/z (%): 348 (M+, 7), 306 (7), 187 (25), 176 (2),
160 (7), 134 (28), 119 (19), 106 (5), 105 (100), 77 (19).
28: Yield: 74%, m.p. 175-176 °C, C20H15N2O4Cl,
Calcd.: C, 62.75; H, 3.95; N, 7.32; Anal.: C, 62.98; H, 4.10;
d : 8.21 (d ´ d, 1H, H-5, 3J = 8.9 Hz, 4J = 2.4 Hz), 7.78-7.52
H
(m, 3H, H-6, H-7, H-8), 7.49-7.31 (m, 3H, Ar-H), 7.30-7.28
(m, 2H, Ar-H), 7.15 (s, 1H, H-3), 6.73 (s, 1H, oxadiazole-
CH), 2.39 (s, 3H, COCH3). IR (KBr) n
1680 (s, C=O),
N, 7.28. d : 7.92 (d, 1H, 5-H, 4J = 2.4 Hz), 7.89-7.86 (m, 3H,
max
H
1640 (s, pyrone C=O), 1604 (S-C=N), 1270 (m, C-O-C). m/z
(%): 334 (M+, 10), 292 (12), 187 (50), 146 (10), 120 (20), 105
(100), 92 (5), 77 (21).
H-7 & Ar-H), 7.72 (d, 1H, H-8, 3J = 8.8 Hz), 7.64-7.55 (m,
2H, Ar-H), 7.17 (s, 1H, H-3), 6.83 (s, 1H, oxadiazole-CH),
2.39 (s, 3H, COCH3), 2.32 (s, 3H, CH3); IR (KBr) nmax 1680
(s, C=O), 1645 (s, pyrone C=O), 1598 (m, C=N), 1280 (m,
C-O-C). m/z (%): 382 (M+, 6), 340 (10), 210 (50), 201 (28),
160 (5), 139 (100), 134 (26), 119(17), 115 (20), 106 (5), 77
(22).
23: Yield: 78%, m.p. 158-159 °C, C19H13N2O4Cl,
Calcd.: C, 61.88; H, 3.55; N, 7.60. Anal.: C, 62.00; H, 3.58;
N, 7.62. d : 8.12 (m, 1H, H-5), 7.76-7.42 (m, 3H, H-6, H-7,
H
H-8), 7.41-7.31 (m, 4H, Ar-H), 7.16 (s, 1H, H-3), 6.71 (s, 1H,
oxadiazole-CH), 2.38 (s, 3H, COCH3). IR (KBr) nmax 1676 (s,
C=O), 1648 (s, pyrone C=O), 1598 (s, C=N), 1275 (m,
C-O-C). m/z (%): 368 (M+, 10), 326 (12), 188 (20), 146 (16),
139 (100), 135 (10), 120 (19), 105 (32), 92 (5), 77 (18).
24: Yield: 76%, m.p. 160-161 °C, C19H13N2O4Cl,
Calcd.: C, 61.88; H, 3.55; N, 7.60. Anal.: C, 61.89; H, 3.54;
29: Yield: 72%, m.p. 184-185 °C, C20H15N2O4Cl,
Calcd.: C, 62.75; H, 3.95; N, 7.32; Anal.: C, 63.01; H, 4.11;
N, 7.18. d : 7.91 (d, 1H, 5-H, 4J = 2.4 Hz), 7.88-7.86 (m, 3H,
H
H-7, Ar-H), 7.72 (d, 1H, H-8, 3J = 8.8 Hz), 7.63-7.55 (m, 2H,
Ar-H), 7.16 (s, 1H, H-3), 6.83 (s, 1H, oxadiazole-CH), 2.39
(s, 3H, COCH3), 2.32 (s, 3H, CH3); IR (KBr) nmax 1678-1648
(s, C=O & pyrone C=O), 1598 (m, C=N), 1282 (m, C-O-C),
1378 (m, -CH3). m/z (%): 382 (M+, 5), 340 (12), 210 (50), 201
(26), 160 (6), 139 (100), 134 (26), 119 (18), 115 (21), 106 (5),
77 (19).
N, 7.62. d : 8.12 (d ´ d, 1H, H-5, 3J = 8.8 Hz, 4J = 2.4 Hz),
H
7.78-7.41 (m, 3H, H-6, H-7, H-8), 7.41-7.32 (m, 3H, Ar-H),
7.18-7.16 (m, 2H, H-3 & Ar-H), 6.72 (s, 1H, oxadiazole-CH),
2.39 (s, 3H, COCH3). IR (KBr) nmax 1680 (s, C=O), 1642 (s,
pyrone C=O), 1596 (s, C=N), 1279 (m, C-O-C). m/z (%): 368
(M+, 5), 326 (12), 188 (56), 139 (100), 120 (17), 105 (20), 92
(6), 77 (31).
30: Yield: 64%, m.p. 150-151 °C, C21H18N2O5, Calcd.:
C, 65.57; H, 4.95; N, 7.65. Anal.: C, 65.48; H, 4.91; N, 7.69.
d : 7.99 (d, 1H, 5-H, 4J = 2.6 Hz), 7.89-7.87 (m, 3H, H-7 &
H
3
25: Yield: 69%, m.p. 155-156 °C, C20H16N2O5, Calcd.:
C, 65.93; H, 4.43; N, 7.69; Anal.: C, 66.00; H, 4.41; N, 7.67.
Ar-H), 7.72 (d, 1H, H-8, J = 9.2 Hz), 7.63-7.55 (m, 2H,
Ar-H), 7.16 (s, 1H, H-3), 6.83 (s, 1H, oxadiazole-CH), 3.57
(s, 3H, OCH3), 2.39 (s, 3H, COCH3), 2.32 (s, 3H, CH3). IR
d : 7.99 (d ´ d, 1H, H-5, 3J = 8.8 Hz, 4J = 2.4 Hz), 7.87-7.68
H
(m, 5H, H-6, H-7, H-8 & Ar-H), 7.68-7.67 (m, 2H, Ar-H),
(KBr) n 1681 (s, C=O), 1640 (s, pyrone C=O), 1590 (m,
max
7.13 (s, 1H, H-3), 6.73 (s, 1H, oxadiazole-CH), 3.84 (s, 3H,
C=N), 1280 (C-O-C). m/z (%): 378 (M+, 8), 336 (10), 201

Synthesis of 2-Dihydrooxadiazolinyl Chromones
J. Chin. Chem. Soc., Vol. 50, No. 4, 2003 907
(25), 206 (16), 135 (100), 160 (5), 134 (26), 119 (21), 106 (4),
77 (19).
Calcd.: C, 55.15; H, 2.92; N, 10.16; Anal.: C, 55.00; H, 2.90;
N, 10.19. d : 8.40-8.38 (m, 2H, Ar-H), 8.13-8.11 (m, 3H, H-5
H
31: Yield: 78%, m.p. 168-169 °C, C20H15N3O6, Calcd.:
C, 61.07; H, 3.84; N, 10.68. Anal.: C, 61.48; H, 3.76; N,
& Ar-H), 7.97 (d ´ d, 1H, H-7, 3J = 8.8 Hz, 4J = 2.4 Hz), 7.65
3
(1H, d, H-8, J = 8.8 Hz), 7.22 (s, 1H, H-3), 6.88 (s, 1H,
10.40. d : 8.40-8.37 (m, 2H, Ar-H), 8.13-8.11 (m, 3H, H-5,
oxadiazole-CH), 2.34 (s, 3H, COCH3). IR (KBr) nmax 1681 (s,
C=O), 1663 (s, pyrone C=O), 1598 (m, C=N), 1521, 1347 (m,
NO2), 1273 (C-O-C). m/z (%): 413 (M+, 3), 371 (17), 221
(53), 154 (5), 150 (100), 139 (7), 126 (11), 104 (34), 98 (8),
77 (22).
H
Ar-H), 7.98 (d×d, 1H, H-7, 3J = 8.8 Hz, 4J = 2.4 Hz), 7.82 (d,
1H, H-8, 3J = 8.8 Hz), 7.23 (s, 1H, H-3), 6.89 (s, 1H,
oxadiazole-CH), 2.39 (s, 3H, COCH3), 2.32 (s, 3H, CH3). IR
(KBr) n 1685 (s, C=O), 1640 (s, pyrone C=O), 1598 (m,
max
C=N), 1521 (m, NO2), 1347 (m, -NO2), 1280 (m, C-O-C). m/z
(%): 393 (5), 350 (7), 201 (25), 160 (5),150 (100), 134 (27),
119 (15), 106 (7), 104 (21), 77 (19).
37: Yield: 70%, m.p. 172-173 °C, C19H13N2O4Br,
Calcd.: C, 55.23; H, 3.17; N, 6.78; Anal.: C, 55.28; H, 3.19;
N, 6.81. d : 8.11 (d, 1H, H-5, 4J = 2.4 Hz), 7.96 (d ´ d, 1H,
H
32: Yield: 76%, m.p. 165-166 °C, C19H13N2O4Cl,
Calcd.: C, 61.88; H, 3.55; N, 7.60. Anal.: C, 62.10; H, 3.49;
H-7, 3J = 8.8 Hz, 4J = 2.4 Hz), 7.81 (m, 3H, Ar-H), 7.63 (d,
1H, H-8, 3J = 8.8 Hz), 7.08-7.72 (m, 3H, H-3), 6.79 (s, 1H,
oxadiazole-CH), 2.29 (s, 3H, COCH3). IR (KBr) nmax 1685 (s,
C=O), 1643 (s, pyrone C=O), 1598 (s, C=N), 1283 (m,
C-O-C). m/z (%): 412 (M+, 3), 370 (8), 307 (2), 265 (12), 225
(4), 199 (6), 196 (15), 171 (7), 143 (5), 105 (100), 77 (30).
38: Yield: 76%, m.p. 149-150 °C, C19H12N2O4BrCl,
N, 7.72. d : 8.11 (d, 1H, H-5, 4J = 2.4 Hz), 7.96 (d ´ d, 1H,
H
H-7, 3J = 8.8 Hz, 4J = 2.4 Hz), 7.82-7.82 (m, 3H, Ar-H), 7.63
3
(d, 1H, H-8, J = 8.8 Hz), 7.09-7.00 (m, 3H, H-3 & Ar-H),
6.88 (s, 1H, oxadiazole-CH), 2.39 (s, 3H, COCH3). IR (KBr)
n
max 1682 (s, C=O), 1645 (s, pyrone C=O), 1598 (m, C=N),
1210 (m, C-O-C). m/z (%): 326 (18), 221 (54), 180 (9), 154
(32), 139 (6), 126 (10), 105 (100), 98 (7), 77 (10).
Calcd.: C, 50.98; H, 2.70; N, 6.26; Anal.: C, 51.00; H, 2.72;
4
N, 6.29. d : 8.10 (d, 1H, H-5, J = 2.4 Hz), 7.96 (d×d, 1H,
H
33: Yield: 74%, m.p. 168-169 °C, C19H12N2O4Cl2,
Calcd.: C, 56.60; H, 3.00; N, 6.95; Anal.: C, 56.54; H, 3.02;
H-7, 3J = 8.8 Hz, 4J = 2.4 Hz), 7.81 (m, 3H, Ar-H), 7.62 (d,
1H, H-8, 3J = 8.8 Hz), 7.72-7.08 (m, 2H, Ar-H), 6.79 (s, 1H,
oxadiazole-CH), 2.32 (s, 1H, COCH3). IR (KBr) nmax 1690 (s,
C=O), 1660 (s, pyrone C=O), 1602 (m, C=N), 1270 (m,
C-O-C), 804 (m, C-Cl), 612 (v, C-Br). m/z (%): 446 (M+, 3),
402 (4), 265 (6), 225 (5), 210 (12), 199 (8), 171 (6), 143 (5),
139 (100), 104 (30), 77 (20).
N, 6.94. d : 7.99 (d, 1H, H-5, 4J = 2.8 Hz), 7.89-7.86 (m, 3H,
H
H-7 & Ar-H), 7.72 (d, 1H, H-8, 3J = 9.2 Hz), 7.64-7.55 (m,
2H, Ar-H), 7.17 (s, 1H, H-3), 6.87 (s, 1H, oxadiazole-CH),
2.32 (s, 3H, COCH3). IR (KBr) n 1680-1644 (s, C=O &
max
pyrone C=O), 1604 (s, C=N), 1259 (m, C-O-C), 621(v, C-Cl).
m/z (%): 361 (18), 221 (50), 180 (10), 154 (6), 139 (100), 126
(10), 115 (34), 98 (8), 77 (20).
39: Yield: 70%, m.p. 152-153 °C, C19H12N2O4BrCl,
Calcd.: C, 50.98; H, 2.70; N, 6.26; Anal.: C, 51.01; H, 2.73;
34: Yield: 70%, m.p. 166-167 °C, C19H12N2O4Cl2,
Calcd.: C, 56.60; H, 3.00; N, 6.95; Anal.: C, 56.55 ; H, 3.01;
N, 6.25. d : 7.98 (d, 1H, H-5, 4J = 2.8 Hz), 7.88-7.86 (m, 3H,
H
H-7 & Ar-H), 7.72 (d, 1H, H-8, 3J = 9.2 Hz), 7.64-7.55 (m,
2H, Ar-H), 7.16 (s, 1H, H-3), 6.82 (s, 1H, oxadiazole-CH),
2.32 (s, 3H, COCH3). IR (KBr) nmax 1690 (s, C=O), 1663 (s,
pyrone C=O), 1602 (m, C=N), 1272 (m, C-O-C), 803 (m,
C-Cl), 611 (v, C-Br). m/z (%): 446 (M+, 3), 402 (2), 265 (8),
225 (5), 210 (14), 199 (5), 184 (9), 171 (6), 143 (5), 139
(100), 104 (28), 77 (20).
N, 7.01. d : 7.99 (d, 1H, H-5, 4J = 2.8 Hz), 7.88-7.86 (m, 3H,
H
H-7 & Ar-H), 7.72 (d, 1H, H-8, 3J = 9.2 Hz), 7.63-7.55 (m,
2H, Ar-H), 7.16 (s, 1H, H-3), 6.82 (s, 1H, oxadiazole-CH),
2.32 (s, 3H, COCH3). IR (KBr) nmax 1682 (s, C=O), 1645 (s,
pyrone C=O), 1596 (s, C=N), 1268 (m, C-O-C). m/z (%): 361
(19), 221 (50), 180 (10), 154 (8), 139 (100), 126 (11), 98 (8),
77 (26).
40: Yield: 70%, m.p. 159-160 °C, C20H15N2O5Br,
Calcd.: C, 54.19; H, 3.41; N, 6.32; Anal.: C, 54.20; H, 3.43;
35: Yield: 72%, m.p. 162-163 °C, C20H15N2O5Cl,
Calcd.: C, 60.24; H, 3.79; N, 7.02; Anal.: C, 60.30; H, 3.81;
N, 6.30. d : 8.11 (d, 1H, H-5, 4J = 2.4 Hz), 7.96 (d ´ d, 1H,
H
N, 7.05. d : 7.99 (d, 1H, H-5, 4J = 2.81 Hz), 7.87-7.80 (m, 3H,
H-7, 3J = 9 Hz, 4J = 2.8 Hz), 7.88-7.86 [m, 2H, Ar-H
(o-OCH3)], 7.65-7.54 (m, 3H, H-8 & Ar-H), 7.16 (s, 1H,
H-3), 6.82 (s, 1H, oxadiazole-CH), 3.51 (s, 1H, OCH3), 2.32
H
3
H-7 & Ar-H), 7.77 (d, 1H, H-8, J = 8.8 Hz), 7.12-7.09 (m,
3H, Ar-H), 6.80 (s, 1H, oxadiazole-CH), 3.84 (s, 3H, OCH3),
2.34 (s, 3H, COCH3). IR (KBr) nmax 1680 (s, C=O), 1645 (s,
pyrone C=O), 1598 (s, C=N), 1280 (m, C-O-C). m/z (%): 356
(19), 221 (51), 154 (6), 135 (100), 139 (8), 140 (60), 126 (10),
98 (7), 77 (20).
(s, 3H, COCH3). IR (KBr) n
1690 (s, C=O), 1660 (s,
max
pyrone C=O), 1598 (m, C=N), 1280 (m, C-O-C), 612 (v,
C-Br). m/z (%): 401 (4), 265 (21), 225 (4), 204 (8), 199 (7),
184 (6), 171 (6), 143 (5), 135 (100), 104 (36), 77 (28).
41: Yield: 80%, m.p. 198-199 °C, C19H12N3O6Br,
36: Yield: 81%, m.p. 201-202 °C, C19H12N3O6Cl,

908 J. Chin. Chem. Soc., Vol. 50, No. 4, 2003
Cao and Cui
Indian J. Chem. 1979, 17B, 37.
Calcd.: C, 49.80; H, 2.64; N, 9.17; Anal.: C, 49.91; H, 2.66;
2. Surredder, P. B.; Garg, C. P.; Kapoor, R. P.; Sharma, C. S.;
Kapil, A. Indian J. Chem. 1995, 34B, 879.
3. Devi, G.; Kapil, R. S.; Pople, S. P. Indian J. Chem. 1979,
19B, 75.
4. Nohara, A.; Hisashi, K.; Taketeshi, S.; Hirosada, S.; Murio,
K.; Yasashi, S. J. Med. Chem. 1977, 20(1), 141.
5. Elderfied, R. C. Ed. Heterocyclic Compounds; John Wiley:
New York, 1951, 2, 343.
N, 9.21. d : 8.40-8.37 [m, 2H, Ar-H (o-NO2)], 8.13-8.11 [m,
H
3H, H-5 & Ar-H (m-NO2)], 7.97 (d ´ d, 1H, H-7, 3J = 8.2 Hz,
4J = 2.4 Hz), 7.65 (d, 1H, 3J = 8.8 Hz), 7.22 (s, 1H, H-3), 6.88
(s, 1H, oxadiazole-CH), 2.34 (s, 3H, COCH3). IR (KBr) n
max
1690 (s, C=O), 1663 (s, pyrone C=O), 1598 (s, C=N), 1521
(m, NO2), 1347 (s, -NO2), 1272 (s, C-O-C), 611 (v, C-Br). m/z
(%): 265 (20), 225 (4), 199 (6), 184 (9), 171 (6), 143 (5), 150
(100), 104 (28), 77 (29).
6. Baker, W. J. Chem. Soc. 1933, 1381.
7. Badcock, G. G.; Dean, F. M.; Alexander, R.; Whalley, W. B.
J. Am. Chem. Soc. 1950, 903.
8. Yang, J.; Hua, W.-T. Huaxue Tongbao 1996, 59(9), 18.
9. Rolf, H.; Rudof, G.; Hans, K.; Renate, K.; Michael, S. Ber.
1964, 97(4), 1085.
10. Khalil, M. A.; EI-Sayed, O. A.; EI-Shamy, H. A. Arch.
Pharm. ( Weinheim ) 1993, 326, 489.
11. El Ashry, E. S. H.; Rashed, N.; Awad, L. F.; Abdel-Rahman,
A. A. H.; Rasheed, H. A. J. Chem. Res. (Miniprint) 2001, 4,
440.
ACKNOWLEDGEMENT
This work was supported by the Natural Science Foun-
dation of the PRC (Grant No. 29962002) and Nankai Univer-
sity State Key Laboratory of Elemento-Organic Chemistry.
Received August 16, 2002.
12. Somogyi, L.; Czuglar, M.; Sohar, P. Tetrahedron 1992,
48(42), 9355.
13. Sami, S. M.; Ibrahim, A. M.; Abdel-Italim, L. Y. Indian. J.
Chem. 1986, 25B, 384.
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