Synthesis and bioactivity of novel bis-heterocyclic compounds containing pyrazole and oxadiazoline

Article abstract of DOI:10.1002/jccs.201190039

Nucleophilic addition of the starting material 3-aryl-1-phenyl-4- formylpyrazoles (1～3) and 4-substi-tuted aryloxyacetyl hydrazine (4a～4e) afford hydrazone compounds containg pyrazolyl (5a～5e, 6a～6e, 7a～7e) in the ethanol. These adducts were refluxed in A

Full text of DOI:10.1002/jccs.201190039

Journal of the Chinese Chemical Society, 2011, 58, 369-375
369
Synthesis and Bioactivity of Novel Bis-heterocyclic Compounds
Containing Pyrazole and Oxadiazoline
Jin-Feng Yang,a,b,* Hong Cao,a Hong Liu,a Bing-Qi Lia and Yan-Mei Maa
aCollege of Chemistry and Chemical Engineering, Shihezi University, Shihezi, Xinjiang, 832002, P. R. China
bKey Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University,
Xinjiang, 832002, P. R. China
Received October 21, 2010; Accepted February 19, 2011; Published Online March 9, 2011
Nucleophilic addition of the starting material 3-aryl-1-phenyl-4-formylpyrazoles (1~3) and 4-substi-
tuted aryloxyacetyl hydrazine (4a~4e) afford hydrazone compounds containg pyrazolyl (5a~5e, 6a~6e,
7a~7e) in the ethanol. These adducts were refluxed in Ac2O and furnished a series of novel bis-hetero-
cyclic compounds. (8a~8e, 9a~9e, 10a~10e) via cyclic reaction. The structures of all newly synthesized
compounds were established by IR, 1H NMR, MS and elemental analysis. New compounds conducted
preliminary tests of antibacterial activities about Fusarium oxyaporium, Verticillium dahliae, Rhizoctonia
solani, Pychium aphanidermatum, Alternaria solani, Sclerotinia sclerotiorum. The results showed that
the inhibiting rate of the bis-heterocyclic compounds (8a~8e, 9a~9e, 10a~10e) was higher than the
pyrazolyl hydrazones (5a~5e, 6a~6e, 7a~7e) obviously.
Keywords: Pyrazole; Oxadiazoline; Synthesis; Bioactivity.
INTRODUCTION
Heterocycles are popularly known for displaying a
wide range of biological properties.1 The structural diver-
sity and biological importance of nitrogen containing het-
erocycles have made them attractive synthetic targets over
many years.2
both chemical and biological purposes.12,13 Oxadiazoline
play a crucial role in the development of theory in hetero-
cyclic chemistry and also are extensively used as useful
synthon in organic synthesis. Also, a number of oxadiazo-
line have been reported to exhibit diverse pharmacological
properties14,15 and antimicrobial activity.16 Therefore, com-
pounds both the pyrazole and the oxadiazoline possess
worthy and imperative bioactivities, which render them
useful substances in organic synthesis. However, bis-het-
erocyclic compounds which contain pyrazole and oxadi-
azoline have rarely been reported. On this basis, our work
has focused on the synthesis of antibacterial compounds.
Therefore, due to the possible importance of these com-
pounds and our interest in the development of heterocy-
cle-based pyrazole, in this paper, we have synthesized a se-
ries of pyrazole carbohydrazide hydrazone derivatives
(5a~5e, 6a~6e, 7a~7e) by reacting appropriately 1-phen-
yl-3-aryl-4-formacyl pyrazoles (1~3) and 4-substituted
aryloxyacetyl hydrazine in ethanol, and some new bis-
heterocycle derivatives (8a~8e, 9a~9e, 10a~10e) based
pyrazole and oxadiazoline in one-step as illustrated in
Scheme I. Specially, we have focused on the preliminary
Oxadiazoline, pyrazole and pyrazoline derivatives
are in general well-known five–membered containing het-
erocyclic compounds. Compounds with pyrazole ring are
of interest due to their broad spectrum of biological activi-
ties against NOS inhibitor,3 monoamine oxidase inhibitor,4
antibacterial,5 antiamoebic.6 Moreover, N-phenylpyrazole
derivatives play an important role in antitumor screening7
as well as potent antimicrobial activity.8 Furthermore, a
number of hydrazide-hydrazone derivatives also have been
claimed to possess interesting bioactivity such as antibacte-
rial-antifungal, anticonvulsant, antiinfloammatory, antima-
larial, analgesic, anticancer acticities.9 So, a few of pyr-
azole carbohydrazide hydrazone derivatives have also been
reported, which have been synthesized in many meth-
ods.10,11
On the other hand, oxadiazoline are important for
* Corresponding author. Tel: 18999737501; E-mail: yjfmht940216@sohu.com

370 J. Chin. Chem. Soc., Vol. 58, No. 3, 2011
Yang et al.
Scheme I
tests of antibacterial activities of new compounds. Our
purpose is that it might be possible to develop new organic
antibacterial activity compounds by satisfactory combi-
nation of pyrazole and oxadiazoline groups through ap-
propriate molecular design and synthesis. The entire in-
vestigated compounds exhibited moderate antibacterial
activityies with the percentage inhibition of six strains,
while bis-heterocyclic compound showed better inhibi-
tory activity than pyrazole carbohydrazide hydrazone de-
rivatives.
NMR spectroscopy, which provided diagnostic tools for
the positional elucidation of the protons. In the 1H NMR
spectra, phenyl protons were observed at the expected
chemical shifts and integral values in all compounds. The
single signal at 8.71-8.41 ppm was assigned to N-H of com-
pounds (5a~5e, 6a~6e, 7a~7e). And, The CH=N proton of
compounds showed single signal at 4.64-4.41 ppm. In ad-
dition, 8.49-8.21 ppm was due to C-H proton of pyrazole
ring. As for the compounds (8a~8e, 9a~9e, 10a~10e), the
signals of N-H and CH=N proton were disappeared after
the ring closure, then proton belonging to the oxadiazoline
ring was observed with the expected chemical shift at
RESULTS AND DISCUSSION
1
The positions of IR band provide significant indica-
tion for the formation of (5a~5e, 6a~6e, 7a~7e) and (8a~
8e, 9a~9e, 10a~10e). The IR spectra of these compounds
exist mainly the bands due to C=N, C=O and C-O-C func-
tional groups. A strong band appeared at 1677-1645 cm-1
was assigned to C=O stretching which shifted to the low
wave number owing to conjugated system. And, the ab-
sorption bands at 1577-1504 cm-1 was attributed to the
C=N stretching vibrations. These compounds (5a~5e, 6a~
6e, 7a~7e) showed sharp bands in the region 3243-3100
cm-1 due to N-H stretching vibrations. In addition, the ab-
sorption bands at 1231-1219 cm-1 was attributed to the
C-O-C, which also confirmed the formation of desired
oxadiazoline ring in the compounds (8a~8e, 9a~9e, 10a~
10e). And the bands due to v(NH) stretch were absent. The
data of the IR spectra of all new compounds are listed in Ta-
ble 2.
8.77-8.43 ppm. The data of H NMR spectra of all new
compounds are listed in Table 2.
The MS (ESI) spectra displayed that all synthesized
compounds had quasi-molecular on peaks; most of which
were the base peaks. The characteristic peaks were ob-
served in the mass spectra of the compounds. The elemen-
tal analysis date and MS data of all new compounds are
listed in Table 1.
As shown in Table 3, all of the tested compounds
showed moderate activities against Alternaria solani,
Sclerotinia sclerotiorum. And, the entire investigated bis-
heterocyclic compounds exhibited good fungicidal activity
with the percentage inhibition of six strains ranged from
45.6 to 97.5, while the most active compounds 10d (R1=Cl,
R2=Br) and 10e (R1=Cl, R2=NO2) among the series exhib-
ited the excellent inhibitory activity (> 85.5%) against six
strains. However, pyrazole carbohydrazide hydrazone de-
rivatives were found to be less active among the tested
compounds. Table 3 perusal of data suggests that the active
Further evidence for the formation of (5a~5e, 6a~6e,
7a~7e) and (8a~8e, 9a~9e, 10a~10e) were obtained by 1H

Bis-heterocyclic Compound, Antibacterial Activity
J. Chin. Chem. Soc., Vol. 58, No. 3, 2011 371
Table 1. Physical data, the elemental analysis and MS data of new compounds
Elemental analysis (calcd.)/%
Compd.
Molecule
Yield/%
m.p./°C
MS m/z (%)
C
H
N
5a
5b
5c
C25H22O3N4
C26H24O3N4
C26H24O4N4
C25H21O3N4Br
C25H21O5N5
C24H19O2N4Br
C25H21O2N4Br
C25H21O3N4Br
C24H18O2N4Br2
C24H18O4N5Br
C24H19O2N4Cl
C25H21O2N4Cl
C25H21O3N4Cl
C24H18O2N4ClBr
C24H18O4N5Cl
C27H24O4N4
81
87
89
88
70
88
82
83
87
74
85
82
83
85
73
79
73
72
76
71
68
74
78
72
61
68
72
78
71
54
192~194
191~192
183~184
204~206
214~215
218~219
225~227
160~161
206~207
247~248
70.47(70.41) 5.22(5.20) 13.11(13.14) 449 ([M+ Na]+, 100)
70.83(70.89) 5.48(5.49) 12.74(12.72) 463 ([M+ Na]+, 100)
68.48(68.41) 5.32(5.30) 12.24(12.27) 479 ([M+Na]+, 100)
59.37(59.42) 4.21(4.19) 11.11(11.09) 528 ([M+ Na]+, 100)
63.76(63.69) 4.48(4.49) 14.83(14.85) 494 ([M+ Na]+, 100)
60.69(60.64) 4.05(4.03) 11.76(11.79) 498 ([M+Na]+, 100)
61.28(61.36) 4.34(4.33) 11.46(11.45) 512 ([M+Na]+, 100)
59.37(59.42) 4.17(4.19) 11.12(11.09) 528 ([M+Na]+, 100)
52.08(52.01) 3.25(3.27) 10.15(10.11) 577 ([M+Na]+, 100)
55.47(55.40) 3.50(3.49) 13.42(13.46) 543 ([M+Na]+, 100)
5d
5e
6a
6b
6c
6d
6e
7a
7b
7c
137~139 66.82(66.90) 4.45(4.44) 13.04(13.01), 454 ([M+Na]+, 100)
124~125
131~132
189~190
213~214
115~116
113~115
118~119
120~121
>250
125~127
136~137
225~226
>250
183~184
120~121
132~133
210~211
196~197
225~227
67.56(67.49) 4.77(4.76) 12.55(12.59) 468 ([M+Na]+, 100)
65.09(65.15) 4.62(4.59) 12.18(12.16) 484 ([M+Na]+, 100)
56.45(56.54) 3.57(3.56) 10.96(10.99) 533 ([M+Na]+, 100)
60.53(60.57) 3.79(3.81) 14.74(14.72) 499 ([M+Na]+, 100)
69.28(69.22) 5.17(5.16) 11.93(11.96) 491 ([M+Na]+, 100)
69.62(69.70) 5.41(5.43) 11.59(11.61) 505 ([M+Na]+, 100)
67.54(67.46) 5.24(5.26) 11.27(11.24) 521 ([M+Na]+, 100)
59.17(59.24) 4.24(4.23) 10.16(10.23) 570 ([M+Na]+, 100)
63.06(63.15) 4.49(4.51) 13.67(13.64) 536 ([M+Na]+, 100)
60.28(60.36) 4.10(4.09) 10.80(10.83) 540 ([M+Na]+, 100)
61.11(61.03) 4.34(4.36) 10.50(10.54) 554 ([M+Na]+, 100)
59.17(59.24) 4.24(4.23) 10.26(10.23) 570 ([M+Na]+, 100)
7d
7e
8a
8b
8c
C28H26O4N4
C28H26O5N4
C27H23O4N4Br
C27H23O6N5
8d
8e
9a
9b
9c
C26H21O3N4Br
C27H23O3N4Br
C27H23O4N4Br
C26H20O3N4Br2
C26H20O5N5Br
C26H21O3N4Cl
C27H23O3N4Cl
C27H23O4N4Cl
C26H20O3N4ClBr
C26H20O5N5Cl
9d
9e
52.30(52.37) 3.39(3.38)
9.43(9.40) 619 ([M+Na]+, 100)
55.60(55.53) 3.57(3.58) 12.49(12.45) 585 ([M+Na]+, 100)
66.14(66.03) 4.50(4.48) 11.81(11.85) 496 ([M+Na]+, 100)
66.68(66.60) 4.75(4.76) 11.48(11.51) 510 ([M+Na]+, 100)
64.40(64.48) 4.58(4.61) 11.16(11.14) 526 ([M+Na]+, 100)
65.65(56.59) 3.67(3.65) 10.22(10.15) 575 ([M+Na]+, 100)
60.23(60.30) 3.87(3.89) 13.56(13.52) 541 ([M+Na]+, 100)
10a
10b
10c
10d
10e
antibacterial compounds could be related to substituent. It
indicated that compounds which substituted electron-with-
drawing groups possess reasonable good antibacteria ac-
tivity as compared to that of electron-donating group. The
preliminary fungicidal activities of these novel compounds
evidenced that the presence of bromine and nitro groups in
the aromatic ring of 5-position and chlorine group in the ar-
omatic ring at the 3-position of the pyrazoline nucleus gave
rise to an increased antibacterial activities. All in all, we
founded that compounds carrying two heterocyclic moi-
eties are more active than those carrying single pyrazole
moiety in our work. Moreover, bis-heterocyclic compounds
containing both pyrazoline and oxadiazoline are important
compounds containing bioactivity that are worthy of doing
research.
EXPERIMENTAL
General method
Melting points were taken on a Yanaco MP-S3 micro-
scopic melting point apparatus. The IR spectra were re-
corded in KBr pellets on a Brucker Equinox-55 FT-IR ap-
paratus. The 1H NMR spectra were recorded on an INOVA-
400 (using TMS as internal standard, DMSO-d6 as sol-
vent). Mass spectra were recorded on an HP 1100 LC-MS
(ESI). Elemental analyses were performed on Perkin-
Elmer 2400 CHN analyzer. All reagents were commercial
products of analytical grade and can be used directly with-
out purification except where they especially noted.
1. Compound 1~3 were prepared according to the re-
ported method17,18
1: Yield 81%, m.p. 136~138 ºC (lit18: m.p. 141~143

372 J. Chin. Chem. Soc., Vol. 58, No. 3, 2011
Yang et al.
Table 2. IR, 1H NMR data of new compounds
Compd.
IR (KBr) n/cm-1
1H NMR (DMSO-d6, 400 MHZ) d
5a
3161 (s, -NH-), 3042 (w, Ar-H), 1666 (s, 8.43 (s, 1H, -NH-CO-), 8.41 (s, 1H, pyrazole-H), 6.94~8.42 (m,
C=O), 1540 (s, C=N)
14H, ph-H), 4.64 (s, 1H, -CH=N-), 3.34 (s, 2H, -CH2O-), 2.50
(3H, s, -OCH3)
5b
5c
5d
5e
3195 (s, -NH-), 3048 (w, Ar-H), 1671 (s, 8.43 (s, 1H, -NH-CO-), 8.29 (s, 1H, pyrazole-H), 6.71~7.52 (m,
C=O), 1503 (s, C=N)
13H, ph-H), 4.64 (s, 1H, -CH=N-), 3.31 (s, 2H, -CH2O-), 3.79
(3H, s, -OCH3), 2.48 (s, 3H, -CH3)
3174 (s, -NH-), 3054 (w, Ar-H), 1645 (s, 8.47 (s, 1H, -NH-CO-), 8.49 (s, 1H, pyrazole-H), 7.26~8.10 (m,
C=O), 1504 (s, C=N)
13H, ph-H), 4.53 (s, 1H, -CH=N-), 3.83 (s, 2H, -CH2O-), 3.56
(3H, s, -OCH3), 3.42 (3H, s, -OCH3)
3190 (s, -NH-), 3047 (w, Ar-H), 1661 (s, 8.64 (s, 1H, -NH-CO-), 8.27 (s, 1H, pyrazole-H), 6.75~7.89 (m,
C=O), 1508 (s, C=N)
13H, ph-H), 4.51 (s, 1H, -CH=N-), 3.57 (s, 2H, -CH2O-), 3.34
(3H, s, -OCH3)
3243 (s, -NH-), 3042 (w, Ar-H), 1666 (s, 8.71 (s, 1H, -NH-CO-), 8.41 (s, 1H, pyrazole-H), 6.73~7.68 (m,
C=O), 1514 (s, C=N)
13H, ph-H), 4.55 (s, 1H, -CH=N-), 3.61 (s, 2H, -CH2O-), 3.34
(3H, s, -OCH3)
6a
6b
3195 (s, -NH-), 3043 (w, Ar-H), 1648 (s, 8.57 (s, 1H, -NH-CO-), 8.21 (s, 1H, pyrazole-H), 6.79~7.32 (m,
C=O), 1577 (s, C=N) 14H, ph-H), 4.41 (s, 1H, -CH=N-), 3.20 (s, 2H, -CH2O-)
3199 (s, -NH-), 3048 (w, Ar-H), 1645 (s, 8.49 (s, 1H, -NH-CO-), 8.34 (s, 1H, pyrazole-H), 7.31~7.42 (m,
C=O), 1510 (s, C=N) 13H, ph-H), 4.52 (s, 1H, -CH=N-), 3.29 (s, 2H, -CH2O-), 2.46 (s,
3H, -CH3)
3174 (s, -NH-), 3054 (w, Ar-H), 1645 (s, 8.49 (s, 1H, -NH-CO-), 8.35 (s, 1H, pyrazole-H), 7.23~7.80 (m,
6c
C=O), 1527 (s, C=N)
13H, ph-H), 4.55 (s, 1H, -CH=N-), 3.24 (s, 2H, -CH2O-), 3.68 (s,
3H, -OCH3)
6d
6e
7a
7b
3183 (s, -NH-), 3061 (w, Ar-H), 1668 (s, 8.46 (s, 1H, -NH-CO-), 8.35 (s, 1H, pyrazole-H), 6.85~7.83 (m,
C=O), 1536 (s, C=N) 13H, ph-H), 4.62 (s, 1H, -CH=N-), 3.31 (s, 2H, -CH2O-)
3198 (s, -NH-), 3042 (w, Ar-H), 1677 (s, 8.47 (s, 1H, -NH-CO-), 8.41 (s, 1H, pyrazole-H), 6.87~7.69 (m,
C=O), 1529 (s, C=N) 13H, ph-H), 4.54 (s, 1H, -CH=N-), 3.29 (s, 2H, -CH2O-)
3174 (s, -NH-), 3059 (w, Ar-H), 1676 (s, 8.43 (s, 1H, -NH-CO-), 8.26 (s, 1H, pyrazole-H), 6.80~7.02 (m,
C=O), 1534 (s, C=N) 14H, ph-H), 4.64 (s, 1H, -CH=N-), 3.34 (s, 2H, -CH2O-)
3195 (s, -NH-), 3048 (w, Ar-H), 1645 (s, 8.49 (s, 1H, -NH-CO-), 8.34 (s, 1H, pyrazole-H), 7.31~7.42 (m,
C=O), 1504 (s, C=N)
13H, ph-H), 4.52 (s, 1H, -CH=N-), 3.29 (s, 2H, -CH2O-), 2.46 (s,
3H, -CH3)
7c
3174 (s, -NH-), 3054 (w, Ar-H), 1645 (s, 8.49 (s, 1H, -NH-CO-), 8.35 (s, 1H, pyrazole-H), 7.23~7.80 (m,
C=O), 1507 (s, C=N)
13H, ph-H), 4.55 (s, 1H, -CH=N-), 3.24 (s, 2H, -CH2O-), 3.68 (s,
3H, -OCH3)
7d
7e
8a
3183 (s, -NH-), 3061 (w, Ar-H), 1668 (s, 8.46 (s, 1H, -NH-CO-), 8.35 (s, 1H, pyrazole-H), 6.85~7.83 (m,
C=O), 1526 (s, C=N) 13H, ph-H), 4.62 (s, 1H, -CH=N-), 3.31 (s, 2H, -CH2O-)
3198 (s, -NH-), 3042 (w, Ar-H), 1677 (s, 8.53 (s, 1H, -NH-CO-), 8.33 (s, 1H, pyrazole-H), 6.87~7.69 (m,
C=O), 1539 (s, C=N) 13H, ph-H), 4.54 (s, 1H, -CH=N-), 3.29 (s, 2H, -CH2O-)
3059 (w, Ar-H), 1666 (s, C=O), 1538 (s, 8.69 (s, 1H, oxadiazole-H), 7.97 (s, 1H, pyrazole-H), 7.34~7.86
C=N), 1256 (s, C-O-C)
(m, 14H, ph-H), 3.81 (s, 2H, -CH2O-), 3.34 (3H, s, -OCH3), 2.23
(s, 3H, -COCH3)
8b
8c
8d
8e
3048 (w, Ar-H), 1671 (s, C=O), 1522 (s, 8.61 (s, 1H, oxadiazole-H), 7.99 (s, 1H, pyrazole-H), 7.48~8.09
C=N), 1220 (s, C-O-C)
(m, 13H, ph-H), 3.83 (s, 2H, -CH2O-), 3.34 (3H, s, -OCH3), 3.29
(s, 3H, -CH3), 2.26 (s, 3H, -COCH3)
3033 (w, Ar-H), 1647 (s, C=O), 1525 (s, 8.63 (s, 1H, oxadiazole-H), 7.87 (s, 1H, pyrazole-H), 7.12~7.86
C=N), 1221 (s, C-O-C)
(m, 13H, ph-H), 3.92 (s, 2H, -CH2O-), 3.75 (3H, s, -OCH3), 3.61
(3H, s, -OCH3), 2.16 (s, 3H, -COCH3)
3059 (w, Ar-H), 1675 (s, C=O), 1521 (s, 8.61 (s, 1H, oxadiazole-H), 8.24 (s, 1H, pyrazole-H), 7.27~7.83
C=N), 1225 (s, C-O-C)
(m, 13H, ph-H), 3.75 (s, 2H, -CH2O-), 3.42 (3H, s, -OCH3), 2.32
(s, 3H, -COCH3)
3071 (w, Ar-H), 1676 (s, C=O), 1513 (s, 8.77 (s, 1H, oxadiazole-H), 8.06 (s, 1H, pyrazole-H), 7.19~7.92
C=N), 1256 (s, C-O-C)
(m, 13H, ph-H), 3.95 (s, 2H, -CH2O-), 3.41 (3H, s, -OCH3), 2.26
(s, 3H, -COCH3)

Bis-heterocyclic Compound, Antibacterial Activity
J. Chin. Chem. Soc., Vol. 58, No. 3, 2011 373
9a
9b
3053 (w, Ar-H), 1659 (s, C=O), 1534 (s, 8.49 (s, 1H, oxadiazole-H), 7.86 (s, 1H, pyrazole-H), 7.19~7.76
C=N), 1220 (s, C-O-C) (m14H, ph-H), 3.31 (s, 2H, -CH2O-), 2.17 (s, 3H, -COCH3)
3069 (w, Ar-H), 1649 (s, C=O), 1513 (s, 8.47 (s, 1H, oxadiazole-H), 7.92 (s, 1H, pyrazole-H), 7.28~7.79
C=N), 1229 (s, C-O-C)
(m, 13H, ph-H), 3.35 (s, 2H, -CH2O-), 2.14 (s, 3H, -COCH3), 2.55
(s, 3H, -CH3)
9c
3042 (w, Ar-H), 1647 (s, C=O), 1546 (s, 8.52 (s, 1H, oxadiazole-H), 7.98 (s, 1H, pyrazole-H), 7.17~7.76
C=N), 1231 (s, C-O-C)
(m, 13H, ph-H), 3.32 (s, 2H, -CH2O-), 3.82 (3H, s, -OCH3), 2.18
(s, 3H, -COCH3)
9d
3068 (w, Ar-H), 1671 (s, C=O), 1529 (s, 8.49 (s, 1H, oxadiazole-H), 8.03 (s, 1H, pyrazole-H), 7.16~7.71
C=N), 1222 (s, C-O-C) (m, 13H, ph-H), 3.35 (s, 2H, -CH2O-), 2.20 (s, 3H, -COCH3)
3073 (w, Ar-H), 1676 (s, C=O), 1526 (s, 8.53 (s, 1H, oxadiazole-H), 7.97 (s, 1H, pyrazole-H), 7.21~7.73
C=N), 1219 (s, C-O-C) (m, 13H, ph-H), 3.34 (s, 2H, -CH2O-), 2.19 (s, 3H, -COCH3)
3051 (w, Ar-H), 1668 (s, C=O), 1548 (s, 8.55 (s, 1H, oxadiazole-H), 7.86 (s, 1H, pyrazole-H), 7.23~7.81
C=N), 1235 (s, C-O-C) (m, 14H, ph-H), 3.31 (s, 2H, -CH2O-), 2.19 (s, 3H, -COCH3)
3059 (w, Ar-H), 1644 (s, C=O), 1523 (s, 8.57 (s, 1H, oxadiazole-H), 7.82 (s, 1H, pyrazole-H), 7.27~7.75
9e
10a
10b
C=N), 1228 (s, C-O-C)
(m, 13H, ph-H), 3.31 (s, 2H, -CH2O-), 2.17 (s, 3H, -COCH3), 2.59
(s, 3H, -CH3)
10c
3062 (w, Ar-H), 1654 (s, C=O), 1531 (s, 8.53 (s, 1H, oxadiazole-H), 7.88 (s, 1H, pyrazole-H), 7.15~7.72
C=N), 1221 (s, C-O-C)
(m, 13H, ph-H), 3.27 (s, 2H, -CH2O-), 3.87 (3H, s, -OCH3), 2.15
(s, 3H, -COCH3)
10d
10e
3064 (w, Ar-H), 1661 (s, C=O), 1522 (s, 8.48 (s, 1H, oxadiazole-H), 7.93 (s, 1H, pyrazole-H), 7.11~7.74
C=N), 1222 (s, C-O-C) (m, 13H, ph-H), 3.25 (s, 2H, -CH2O-), 2.27 (s, 3H, -COCH3)
3078 (w, Ar-H), 1665 (s, C=O), 1524 (s, 8.43 (s, 1H, oxadiazole-H), 7.91 (s, 1H, pyrazole-H), 7.20~7.67
C=N), 1224 (s, C-O-C)
(m, 13H, ph-H), 3.24 (s, 2H, -CH2O-), 2.29 (s, 3H, -COCH3)
ºC);
ºC);
ºC);
4. General procedure for the preparation of 3-(sub-
2: Yield 88%, m.p. 140~142 ºC (lit18: m.p. 138~139
3: Yield 89%, m.p. 141~143 ºC (lit18: m.p. 139~141
stituted)aryl-4-(3-acetyl-2-aryloxylmethylene-1,3,4-
oxadiazoline-5)-1-phenyl-2-pyrazoline (8a~8e,
9a~9e, 10a~10e)
A solution of the corrsponding hydrazone (5a~5e,
6a~6e, 7a~7e) (2 mmol) in acetic anhydride was refluxed
for 1 h. the completion was monitored by (TLC, 1:1
MeOH-CCl3H). The solution was filtered and poured into
iced water to give the crude product. The solid subse-
quently was washed by water, then recrystallized from ace-
tone to give compound as colorless crystals.
2. Compounds 4a-4e were prepared according to the
reported method19
4a: Yield 71%, m.p. 112~ 113 ºC; (lit19: 111~112 ºC);
4b: Yield 73%, m.p. 137~138 ºC; (lit19: 134~136 ºC);
4c: Yield 80%, m.p. 141~142 ºC; (lit19: 135~136 ºC);
4d: Yield 74%, m.p. 172~173 ºC; (lit19: 171~172 ºC);
4e: Yield 68%, m.p. 189~191 ºC;
5. Fungicidal evaluation (5a~5e, 6a~6e, 7a~7e, 8a~8e,
9a~9e, 10a~10e)
3. General procedure for the preparation of hydra-
zone compounds containg pyrazolyl (5a~5e, 6a~6e,
7a~7e)
The antibacterial activities of the synthesized com-
pounds, which against six strains such as Fusarium
oxyaporium, Verticillium dahliae, Rhizoctonia solani,
Pychium aphanidermatum, Alternaria solani, Sclerotinia
sclerotiorum, were carried out by the reported method.11,12,20
Compounds 500 mg (anhydrous), which dissolved in 150.0
mL of sterilized DMF, were diluted with sterilized DMF to
make 500 mg/L sample solutions. 2 mL of sterilized sample
solution were mixed with 18 mL PDA to make 50 mg/L test
culture medium. The center of medium containing the test
4-Substituted aryloxyacetyl hydrazine 4a~4e (5.5
mmol) and 1-phenyl-3-aryl-4-formylpyrazoles (1~3) (5.0
mmol) in ethanol (30 mL) was refluxed (incorporating) in
the presence of a catalytic amount of glacial acetic acid.
(TLC, 1:1 EtOAc-petroleum ether) for 3~3.5 h. The solu-
tion was filtered and concentrated under reduced pressure
to afford crude produce, which was recrystallized from
DMF as colorless crystals.

374 J. Chin. Chem. Soc., Vol. 58, No. 3, 2011
Yang et al.
Table 3. Fungicidal activities of new compounds
Inhibition rate /%
Compd.
Fusarium
Verticillium Rhizoctonia Pychiumaph
Alternaria
solani
Sclerotinia
oxyaporium
dahliae
solani
anidermatum
sclerotiorum
5a
5b
5c
32.06
38.35
38.84
69.31
69.93
44.46
51.55
60.02
61.56
63.67
32.06
29.47
28.26
69.54
67.39
81.70
85.59
92.23
94.75
97.31
94.18
92.27
94.34
94.27
95.86
88.67
92.51
91.36
91.85
95.74
19.76
30.92
27.70
49.32
45.62
31.45
45.41
47.01
64.46
61.96
38.73
47.63
47.06
66.80
68.61
62.65
69.17
73.03
77.74
78.12
71.17
74.54
71.78
78.76
74.36
76.45
79.17
76.34
86.38
88.52
1.00
30.64
23.42
56.20
53.40
6.77
16.06
48.40
50.36
56.91
9.52
13.25
35.07
43.76
55.53
55.85
77.45
80.97
79.32
92.89
86.39
91.37
92.05
97.26
97.84
84.92
89.31
89.67
95.18
96.06
8.97
6.79
7.68
50.77
64.16
63.89
76.79
74.34
50.85
57.92
53.35
73.55
71.52
48.71
56.16
55.53
75.53
73.62
45.31
80.03
82.50
89.05
87.68
83.50
84.47
82.83
88.12
89.92
81.98
94.58
93.61
97.36
97.49
57.03
60.89
60.86
75.27
74.53
54.36
67.85
59.98
71.77
70.34
57.00
64.20
63.41
74.63
71.31
74.46
83.18
84.38
89.13
89.71
71.76
74.74
73.45
89.65
89.62
86.12
92.88
94.76
96.83
96.49
5d
5e
55.32
39.76
16.47
52.67
31.35
60.25
63.80
29.55
29.80
28.57
65.76
59.98
76.61
80.26
80.76
87.01
90.11
77.76
82.68
87.88
85.00
85.80
85.29
90.16
76.36
92.86
91.64
6a
6b
6c
6d
6e
7a
7b
7c
7d
7e
8a
8b
8c
8d
8e
9a
9b
9c
9d
9e
10a
10b
10c
10d
10e
compounds delivered approximately 500 mm external di-
ameter of bacilli cells in every three repetition. The sam-
ples were incubated aseptically at 26 °C for 48 ~ 72 h. By
comparison, the medium without any test compound/DMF
(sterilized) was also inoculated with the test organism to
check whether the media supports the growth of the anti-
bacterial activities or not.
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