Synthesis of 3-(3′-acetyl-5′-aroyl-1′,3′,4′ - oxadiazolyl-2′)-chromones

Article abstract of DOI:10.1023/A:1013754030975

A general method has been proposed for synthesizing 3-(3′-acetyl-5′-aroyl-1′,3′,4′ -oxadiazolyl-2′)-chromones that has been based on conversion of 3-formylchromones to acylhydrazones and of the acylhydrazones into the heterocyclic chromones.

Full text of DOI:10.1023/A:1013754030975

Chemistry of Natural Compounds, Vol. 37, No. 4, 2001
SYNTHESIS OF 3-(3 -ACETYL-5 -AROYL-1 ,3 ,4 -
-OXADIAZOLYL-2 )-CHROMONES
L. Tsao,2 L. Chzhan,1 and Ts. Lyu1
UDC 547.814.5
A general method has been proposed for synthesizing 3-(3 -acetyl-5 -aroyl-1 ,3 ,4 -oxadiazolyl-2 )-
chromones that has been based on conversion of 3-formylchromones to acylhydrazones and of the
acylhydrazones into the heterocyclic chromones.
Key words: substituted 3-formylchromones, aroylhydrazones, 3-(3 -acetyl-5 -aroyl-1 ,3 ,4 -oxadiazolyl-2 )-chromones.
3-Heterylchromones are known to possess a wide spectrum of biological activity including antiallergic, anticholesteric,
hypolipidemic, antimicrobial, fungicidal, and antiblastic activities and act as CNS stimulants [1]. Therefore, much attention
has recently been paid to the synthesis of new compounds.
Methods for synthesizing 3-heterylchromones have been reviewed [1]. Two principal approaches are known:
construction of the chromone system from substituted α-hetaryl-2-hydroxyacetophenones with the appropriate reagents and
introduction of a heterocycle into an existing chromone system.
We selected the second approach for synthesizing previously unknown (but promising for resolving scientific issues)
3-(3 -acetyl-5 -aroyl-1 ,3 ,4 -oxadiazolyl-2 )-chromones (3) that is based on the use of available 3-formylchromone (1) [2].
Reaction of 3-formylchromone and aroylhydrazines produced the corresponding aroylhydrazones 2a-l. Then, reaction
with acetic anhydride gave 3-(3 -acetyl-5 -aroyl-1 ,3 ,4 -oxadiazolyl-2 )-chromones (3a-l).
1
R
1
R
1
R
COCH
3
O
O
O
O
O
Ac O
2
EtOH
AcOH
N
N
+
ArCONHNH
2
reflux
2
R
2
R
2
R
CHO
CH=N NHCAr
Ar
O
O
O
2 a - l
3 a -l
1 a-l
2-3
R1
R2
Ar
C6H5
-ClC6H4
-CH3OC6H4
-NO2C6H4
C6H5
-ClC6H5
-CH3OC6H4
-NO2C6H4
C6H5
a
b
c
d
e
f
g
h
i
H
H
H
H
H
H
H
H
Cl
Cl
Cl
Cl
CH3
CH3
CH3
CH3
Br
Br
Br
Br
Cl
o
p
p
p
p
o
p
o
j
k
l
Cl
Cl
Cl
-ClC6H5
-CH3OC6H4
-NO2C6H4
p
1) Sin tszyan University, PRC, 830046, Urumchi, Shen lilu, 14, e-mail: clhJ@xju.edu.cn; 2) Nankai University, PRC.
Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 267-269, July-August, 2001. Original article submitted August
6, 2001.
0009-3130/01/3704-0311$25.00 ©2001 Plenum Publishing Corporation
311

TABLE 1. Properties of Compounds 2-3
Compound
Empirical formula
Yield, %
mp, oC
2a
2b
2c
2d
2e
2f
C18H14N2O3
C18H13ClN2O3
C19H16N2O4
85
75
60
57
88
72
62
70
82
60
55
51
80
52
47
43
79
51
47
42
83
52
44
54
209-210
234-235
214-216
235-236
217-218
197-198
207-208
195-196
211-213
176-177
188-190
283-284
173-174
187-188
248-249
222-224
215-216
206-207
233-234
228-229
136-137
204-205
239-241
212-214
C18H13N3O5
C17H10BrN2O3
C17H10ClBrN2O4
C18H13BrN2O4
C17H10BrN3O5
C17H10Cl2N2O3
C17H9Cl3N2O3
C18H12Cl2N2O4
C17H9Cl2N3O5
C20H16N2O4
2g
2h
2i
2j
2k
2l
3a
3b
3c
3d
3e
3f
C20H15ClN2O4
C21H18N2O5
C20H15N3O6
C19H13BrN2O4
C19H12ClBrN2O4
C20H15BrN2O5
C19H14BrN3O6
C19H12Cl2N2O4
C19H11Cl3N2O4
C20H14Cl2N2O5
C19H11Cl2N3O6
3g
3h
3i
3j
3k
3l
The structures of 2 and 3 (Table 1) were confirmed using analytical data (analytical results for the synthesized
compounds agreed with those calculated) and PMR, IR, and mass spectra. The PMR and mass spectral results for 2a-l and 3a-l
are listed in Table 2.
The IR spectra of 2a-l exhibit characteristic absorption bands (cm-1) at 3100-3200 (NH), 1660-1670 (C O), 1620-1640
(C N), and 1590-1610 (cyclochromones).
The PMR spectra of 2a-l contain signals (ppm) at 8.5-9.0 (2-H proton of the pyrone ring) and 11.8-12.2 (NH proton).
+
The peak for the molecular ion is weak owing to the instability of the aroylhydrazones. The appearance of [M - ArCO] peaks
indicates that the acidic amide bond is readily cleaved. The chromone ring undergoes a reverse Diels—Alder reaction to
produce a fragment. Then, CO groups are lost stepwise.
Absorption bands (cm-1) at 3100-3200 disappear in the IR spectra of 3a-l. Bands characteristic of the chromone moiety
(1592-1620), heterocycles (1475-1510), and acetyl groups (1750-1760) appear. The PMR spectra lack signals at 11.8-12.2 ppm.
This indicates that heterocyclic compounds containing the oxadiazolyl fragment are already prepared. The 2-H proton of the
pyrone ring appears in the spectra of 3 as a narrow signal at 8.8-8.9 ppm [3].
The study of the mass spectra of 3a-l showed that the peak for the molecular ion is also weak (usually <10%). The base
+
peak is [M - COCH ] . The chromone ring cleaves via a reverse Diels—Alder reaction, etc.
3
312

TABLE 2. PMR and Mass Spectra of Compounds 2-3
Compound
PMR, δ, ppm
Mass, m/z
2a
2b
2c
12.21 (1H, br.s, NH), 8.87 (1H, s, 2-H), 7.24-7.98 (9H, m, CH=N, 5, 7, 8-H, Ar-H), 2.31 (3H, s, CH3)
12.15 (1H, br.s , NH), 8.77 (1H, s, 2-H), 7.23-7.92 (8H, m, CH=N, 5, 7, 8-H, Ar-H), 2.31 (3H, s, CH3)
12.08 (1H, br.s , NH), 8.70 (1H, s, 2-H), 7.28-8.10 (8H, m, CH=N, 5, 7, 8-H, Ar-H), 2.31 (3H, s, CH3),
3.56 (3H, s, OCH3)
306
341
336
2d
2e
2f
11.89 (1H, br.s , NH), 8.76 (1H, s, 2-H), 7.12-8.21 (8H, m, CH=N, 5, 7, 8-H, Ar-H)
11.98 (1H, br.s , NH), 8.79 (1H, s, 2-H), 7.22-8.19 (9H, m, CH=N, 5, 7, 8-H, Ar-H)
11.89 (1H, br.s, NH), 8.76 (1H, s, 2-H), 7.12-8.21 (8H, m, CH=N, 5, 7, 8-H, Ar-H)
12.00 (1H, br.s , NH), 8.52 (1H, s, 2-H), 7.23-8.25 (8H, m, CH=N, 5, 7, 8-H, Ar-H), 3.66 (3H, s,
OCH3)
351
370
422
401
2g
2h
2i
11.95 (1H, br.s , NH), 8.92 (1H, s, 2-H), 7.23-8.25 (8H, m, CH=N, 5, 7, 8-H, Ar-H)
12.02 (1H, br.s , NH), 8.58 (1H, s, 2-H), 7.23-8.33 (8H, m, CH=N, 5, 7-H, Ar-H)
11.83 (1H, br.s , N-H), 8.97 (1H, s, 2-H), 7.21 8.17 (7H, m, CH=N, 5, 7-H, Ar-H)
11.98 (1H, br.s, N-H), 8.97 (1H, s, 2-H), 7.13 8.32 (7H, m, CH=N, 5, 7-H, Ar-H), 3.66 (3H, s,
OCH3)
416
361
396
391
2j
2k
2l
12.10 (1H, br.s , N-H), 8.95 (1H, s, 2-H), 7.22 8.38 (7H, m, CH=N, 5, 7-H, Ar-H)
8.83 (1H, s, 2-H), 8.39 7.28 (8H, m, 5, 7, 8-H, ph-H), 7.01 (1H, s, 2 -H), 2.33 (3H, s, CH3),
2.37 (3H, s, COCH3)
406
348
2a
3b
3c
8.89 (1H, s, 2-H), 8.29 7.25 (7H, m, 5, 7, 8-H, ph-H), 7.07 (1H, s, 2 -H), 2.30 (3H, s, CH3),
2.35 (3H, s, COCH3)
383
378
8.92 (1H, s, 2-H), 8.23 7.16 (7H, m, 5, 7, 8-H, ph-H), 7.09 (1H, s, 2 -H), 2.28 (3H, s, CH3),
2.37 (3H, s, COCH3), 3.59 (3H, s, OCH3)
3d
3e
3f
8.81 (1H, s, 2-H), 8.39 7.28 (7H, m, 5, 7, 8-H, ph-H), 7.12 (1H, s, 2 -H), 2.28 (3H, s, COCH3)
8.87 (1H, s, 2-H), 8.31 7.22 (7H, m, 5, 7, 8-H, ph-H), 7.07 (1H, s, 2 -H), 2.37 (3H, s, COCH3)
8.79 (1H, s, 2-H), 8.35 7.18 (7H, m, 5, 7, 8-H, ph-H), 7.12 (1H, s, 2 -H), 2.28 (3H, s, COCH3)
8.95 (1H, s, 2-H), 8.28 7.12 (7H, m, 5, 7, 8-H, ph-H), 7.09 (1H, s, 2 -H), 2.28 (3H, s, COCH3),
3.62 (3H, s, OCH3)
393(4), 350 (100)
413
448
443
3g
3h
3i
8.91 (1H, s, 2-H), 8.25 7.10 (7H, m, 5, 7, 8-H, ph-H), 7.03 (1H, s, 2 -H), 2.39 (3H, s, COCH3)
8.88 (1H, s, 2-H), 8.13 7.22 (7H, m, 5, 7-H, ph-H), 7.15 (1H, s, 2 -H), 2.37 (3H, s, COCH3)
8.91 (1H, s, 2-H), 8.28 7.23 (6H, m, 5, 7-H, ph-H), 7.09 (1H, s, 2 -H), 2.28 (3H, s, COCH3)
8.91 (1H, s, 2-H), 8.19 7.18 (6H, m, 5, 7-H, ph-H), 7.03 (1H, s, 2 -H), 2.38 (3H, s, COCH3),
3.65 (3H, s, OCH3)
460
403
438
433
3j
3k
3l
8.94 (1H, s, 2-H), 8.25 7.13 (6H, m, 5, 7-H, ph-H), 7.00 (1H, s, 2 -H), 2.31 (3H, s, COCH3)
448
EXPERIMENTAL
GF-254 plates were used for TLC. Melting points were measured on an MP-S3 (Japan) heating stage. An automated
MT-3 analyzer was used for elemental analysis. IR spectra were recorded on a Bruker FT-IR Equinox-55 (KBr) instrument;
1
PMR spectra, on a Bruker AX 80 ( H, 80 MHz) spectrometer in CDCl or DMSO-d with TMS internal standard; mass spectra,
3
6
on an HP 5988 AMS instrument.
General Method for Preparing Aroylhydrazones 2a-l. A mixture of equivalent amounts of 1 and aroylhydrazones
prepared according to the literature method [2, 4] was dissolved in ethanol (95%), treated with several drops of glacial acetic
acid, and refluxed for 5-6 h. The crystals that precipitated after cooling were filtered off and recrystallized from absolute ethanol
to give 2a-l.
General Method for Preparing Aroylhydrazones 3a-l. Aroylhydrazones 2a-l (2 mmole) were treated with acetic
anhydride and stirred and boiled for 2 h. The reaction mixture was cooled and poured into ice water. The precipitate was
filtered off, washed with water, dried, and recrystallized from DMF/EtOH/H O to give 3a-l.
2
313

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3.
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Izd. Rostov Univ., Rostov (1985), p. 129.
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