Synthesis and antibacterial activities of 2-(1-aryl-5-methyl-1,2,3-triazol- 4-yl)-1,3,4-oxadiazole derivatives

Article abstract of DOI:10.1002/jccs.200200057

Eighteen novel 2-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-1,3,4-oxadiazole derivatives and two acylhydrazone intermediate compounds were synthesized by various pathways starting from 1-aryl-5-methyl-1,2,3-triazol-4-formhydrazide (1). All products were identified by spectroscopic analysis, and 2-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-5-benzalthio-1,3,4-oxadiazole was further validated by X-ray crystallography. Results from primary antibacterial activity tests indicated that most of the compounds were effective against E. coli, P. aeruginosa, B. subtilis and S. aureus.

Full text of DOI:10.1002/jccs.200200057

Journal of the Chinese Chemical Society, 2002, 49, 369-373
369
Synthesis and Antibacterial Activities of
2-(1-Aryl-5-methyl-1,2,3-triazol-4-yl)-1,3,4-oxadiazole Derivatives
Yan Zhanga (
), Ren-Zhong Qiaoa (
Zi-Yi Zhanga* ( ), Qin Wangb (
Li-Min Maob ( ) and Kai-Bei Yuc (
), Peng-Fei Xua* (
),
),
)
aCollege of Chemistry and Chemical Engineering, National Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou, 730000, P. R. China
bCollege of Life Science, Lanzhou University, Lanzhou, 730000, P. R. China
cAnalysis & Research Center, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences,
Chengdu, 610041, P. R. China
Eighteen novel 2-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-1,3,4-oxadiazole derivatives and two acylhy-
drazone intermediate compounds were synthesized by various pathways starting from 1-aryl-5-methyl-
1,2,3-triazol-4-formhydrazide (1). All products were identified by spectroscopic analysis, and 2-(1-aryl-5-
methyl-1,2,3-triazol-4-yl)-5-benzalthio-1,3,4-oxadiazole was further validated by X-ray crystallography. Re-
sults from primary antibacterial activity tests indicated that most of the compounds were effective against E.
coli, P. aeruginosa, B. subtilis and S. aureus.
INTRODUCTION
1,3,4-Oxadiazole derivatives are becoming an impor-
can also be obtained by reactions of RCONHNH2 with either
R2COOH or CS2 directly.8-9 We synthesized 2-(1-aryl-5-
methyl-1,2,3-triazole-4-yl)-5-mercapto-1,3,4-oxadiazole (2)
by the latter pathway in order to avoid corrosive reagents
such as POCl3, PbO2 and Pb(OAC)4. Our synthetic procedure
of compounds 3~5 and 7~9 were completed mostly in water
without PTC, which differs from previous literature re-
ports.10
tant member in the heterocyclic family not only because of
their wide usage as dyes, photosensitive and electrical mate-
rial,1 but also because of their broad spectrum in biological
activities such as HIV-activity, antibacterial and antifungal
activities.2 1,2,3-Triazole and related compounds have at-
tracted much attention in more and more reports due to their
indispensable roles in both agriculture and industry. In recent
years, incorporation of 1-substituted benzyl-1,2,3-triazole
moiety with 1,3,4-oxadiazoles in the same molecule yielded
promising results.3-4 Combining 1-aryl-5-methyl-1,2,3-tri-
azole with substituted 1,3,4-oxadiazole is expected to give
new compounds with better biological activities. In this re-
port, synthesis of 2-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-5-
mercapto-1,3,4-oxadiazole (2) was accomplished starting
from 1-aryl-5-methyl-1,2,3-triazol-4-formhydrazide (1).
Some reactions of 2 were studied, such as Mannich reaction,
methylated reaction, as well as the reactions with halide and
aldehyde for the production of new compounds 3-11.
Products 2~11 formed distinct crystals, and their struc-
tures were confirmed by elemental analysis and spectral data
(Table 1 and 2). In IR spectra, the two absorption bands at
1617~1640 cm-1 and 1255~1299 cm-1 are assigned to C=N
and N-N=C functional groups, whereas the absorption bands
at 1066~1083 cm-1 and 965~987 cm-1 are characteristic of
C-O-C and N-N=N according to the literature.11-12 The mo-
lecular ions of 6 can be detected by FAB-MS, but not by
EI-MS due to the weak N-CH2-N bond. The 1H NMR spectra
of 2 in DMSO-d6 displayed singlets at 14.51~14.80 ppm for
NH, indicating that the compounds existed mainly in thione-
form. According to previous results, protons of S-CH2- in
3~5 to 8~9 appeared at 4.23~4.51 ppm and 3.21~3.82
ppm, respectively. The difference in chemical shift is caused
by functional groups attached to the S-CH2-, which are either
strong electron withdrawing substituents (phenyl and car-
bonyl) or weak electron withdrawing (methylene).10,13
Compound 3a was dissolved in hot ethyl acetate-
petroleum and filtrated. Evaporation of the solvent after 18 h
gave colorless crystals suitable for X-ray crystallography.
RESULTS AND DISCUSSION
2,5-Substituted-1,3,4-oxadiazole derivatives can be
prepared from intermediate RCONHNHCOR2 or RCONHN=
CHR2 via dehydration or oxidantion.3-7 Alternatively, they

370 J. Chin. Chem. Soc., Vol. 49, No. 3, 2002
Zhang et al.
Scheme I
N
N
N
N
N
N H
O
N
N
SR'
NHNH
2
N
N
N
N
SH
N
N
O
S
O
O
CH
3
i
ii
CH
CH
CH
3
N
R
3
3
N
R
N
R
N
R
R' = CH2C6H5 (3),
CH2COC6H5 (4),
CH2COOH (5).
1
2
3~5
iii
iv
v
H
C
2
H
N
N
N
N
N
N
N
N
N
CH
3
N
S
(CH )
2 n
S
N
N
SCH
3
N
N
N
N
O
S
O
O
O
N
CH
CH
3
3
H C
3
CH
N
3
N
R
N
R
N
6
7
8~9 n = 2 (8), 4 (9).
R
R
O
O
N
N
CH
3
N
CH
Cl
N
N
N
H
H
N
O
vi
CH
Cl
3
vii
N
N
CH
R = H (a), CH (b)
3
3
N
R
10
11
R
i: CS2/KOH/C2H5OH/reflux; HCl; ii: H2O/NaOH ClCH2C6H5/r.t.(3) or BrCH2COC6H5/EtOH/reflux (4) or
ClCH2COOH(5)/reflux; iii: C2H5OH/HCHO/p-CH3C6H4NH2, r.t.; iv: H2O/NaOH/(CH3O)2SO2, r.t.; v: H2O/NaOH,
ClCH2CH2Cl(8) or Br(CH2)4Br(9), reflux; vi: EtOH/p-ClC6H4CHO/TsOH, reflux; vii: Ac2O, reflux.
Table 1. Physical Properties and Elemental Analysis of Compounds 2-11
Elemental anal. Found (Calcd.)/%
No.
Crystals
m.p. (ºC)
yield
Formula
N %
C %
H %
2a
2b
3a
3b
4a
4b
5a
5b
6a
6b
7a
7b
8a
8b
9a
9b
White plates
White plates
Colorless crystals
White needles
White plates
White plates
Pale brown plates
White plates
Pale yellow needles
White plates
White powder
Pale yellow needles
White granules
White needles
White plates
205-207
224-226
62-64
78
83
82
86
85
90
80
82
85
88
72
76
83
84
85
90
94
95
76
79
C11H9N5OS
26.73 (27.01)
25.48 (25.62)
19.96 (20.04)
18.97 (19.27)
18.57 (18.56)
17.47 (17.89)
21.80 (22.07)
21.24 (21.14)
22.25 (22.21)
21.11 (21.41)
25.37 (25.62)
24.48 (24.37)
25.53 (25.72)
23.99 (24.46)
23.86 (24.46)
23.17 (23.32)
20.82 (20.61)
19.62 (19.79)
18.60 (18.34)
18.02 (17.69)
50.63 (50.96)
52.55 (52.74)
61.72 (61.88)
62.61 (62.79)
60.05 (60.47)
61.32 (61.36)
49.29 (49.21)
50.71 (50.75)
60.17 (60.30)
61.17 (61.21)
52.46 (52.74)
54.42 (54.34)
52.68 (52.93)
54.32 (54.53)
54.11 (54.53)
55.76 (55.98)
60.40 (60.09)
61.29 (61.11)
59.44 (59.77)
60.33 (60.69)
3.74 (3.40)
4.31 (4.06)
4.56 (4.33)
4.31 (4.71)
4.22 (4.06)
4.69 (4.38)
3.52 (3.49)
3.96 (3.95)
4.98 (4.77)
5.28 (5.14)
4.19 (4.06)
4.66 (4.56)
3.91 (3.70)
4.35 (4.22)
4.55 (4.22)
5.04 (4.70)
4.36 (4.15)
4.63 (4.56)
4.29 (4.22)
4.82 (4.58)
C12H11N5OS
C18H15N5OS
C19H17N5OS
C19H15N5O2S
C20H17N5O2S
C13H11N5O3S
C14H13N5O3S
C19H18N5O2S
C20H20N5O2S
C12H11N5OS
C13H13N5OS
C24H20N10O2S2
C26H24N10O2S2
C26H24N10O2S2
C28H28N10O2S2
C17H14N5ClO
C18H16N5ClO
C19H16N5ClO2
C20H18N5ClO2
112-114
136-138
177-179
175-177
162-164
145-147
156-158
94-96
143-145
197-199
202-204
152-154
194-196
228-230
238-240
225-227
236-237
White powder
10a White plates
10b Long white needles
11a White plate
11b White needles

2-(1-Aryl-5-methyl-1,2,3-triazol-4-yl)-1,3,4-oxadiazole
J. Chin. Chem. Soc., Vol. 49, No. 3, 2002 371
Table 2. IR, MS and 1H NMR Data of Compounds 2-11
No.
IR max/cm-1
EI-MS (%)
1H NMR
2a
3101, 1631, 1279,
1067, 983
3101, 1633, 1278,
1067, 987
3028, 1617, 1278,
1071, 973
3062, 1617, 1270,
1068, 976
3048, 1676, 1624,
1290, 1071, 971
3063, 1686, 1626,
1296, 1070, 977
2936, 1718, 1624,
1267, 1073, 978
2937, 1720, 1624,
1261, 1075, 980
3328, 1635, 1272,
1082, 975
259 (M+, 28), 230 (25), 170 (100),
130 (32), 103 (10), 77 (69)
273 (M+, 15), 245 (19), 184 (44),
170 (78), 91 (100)
14.80 (s, 1H, NH), 7.67 (s, 5H, ArH),
2.53 (s, 3H, CH3)
14.51 (s, 1H, NH), 7.63 (broad, 4H, ArH),
2.51, 2.43 (2s, 6H, 2CH3)
7.50~7.58 (m, 10H, ArH), 4.58 (s, 2H, CH2),
2.72 (s, 3H, CH3)
7.52~7.29 (m, 9H, ArH), 4.57 (s, 2H, CH2),
2.68, 2.49 (2s, 6H, 2CH3)
8.12~7.57 (m, 10H, ArH), 5.21 (s, 2H, CH2),
2.57 (s, 3H, CH3)
8.13~7.50 (m, 9H, ArH), 5.20 (s, 2H, CH2),
2.54, 2.43 (2s, 6H, 2CH3)
13.19 (s, 1H, OH), 7.67 (s, 5H, ArH),
4.23 (s, 2H, CH2), 2.58 (s, 3H, CH3)
13.31 (s, 1H, OH), 7.53~7.50 (m, 4H, ArH),
4.23 (s, 2H, CH2), 2.56, 2.43 (2s, 6H, 2CH3)
7.65~7.68 (m, 9H, ArH), 6.10 (s, 2H, CH2),
5.54 (s, 1H, NH), 2.54, 2.31 (2s, 6H, 2CH3)
7.47~6.89 (m, 9H, ArH), 6.08 (s, 2H, CH2),
5.53 (s, 1H, NH), 2.51, 2.42, 2.22 (3s, 9H,
3CH3)
2b
3a
3b
4a
4b
5a
5b
6a
6b
----
363 (M+, 4), 262 (7), 172 (7), 132 (8),
115 (10), 91 (100), 65 (23)
377 (M+, 11), 349 (4), 179 (10), 156 (23),
118 (27), 105 (100), 77 (57)
391 (M+, 26), 363 (29), 273 (2), 170 (46),
105 (100), 91 (44), 65 (14)
317 (M+, 82), 289 (7), 158 (100),
156 (33), 130 (56), 118 (84), 77 (65)
----
273 (2), 260 (15), 259 (100), 170 (13), 155
(21), 91 (17), 77 (16), 379 (M+1, FAB)
317 (3), 273 (100), 198 (10), 184 (19), 169
(44), 91 (21), 65 (13), 393 (M+1, FAB)
3324, 1640, 1271,
1082, 976
7a
7b
8a
8b
9a
3029, 1622, 1257,
1072, 977
3043, 1620, 1255,
1072, 980
3044, 1620, 1265,
1066, 974
3044, 1623, 1271,
1070, 973
7.58 (s, 5H, ArH), 2.81 (s, 3H, SCH3), 2.70
(s, 3H, CH3)
7.60 (broad, 4H, ArH), 2.82 (s, 3H, SCH3),
2.72, 2.65 (2s, 6H, 2CH3)
7.65 (s, 10H, ArH), 3.82 (s, 4H, S-CH2-
CH2-S), 2.58 (s, 6H, 2CH3)
7.48 (br, 8H, ArH), 3.81 (s, 4H, S-CH2-
CH2-S), 2.56, 2.43 (2s, 12H, 2*2CH3)
7.67 (s, 10H, ArH), 3.40~3.31 (m, 4H,
2SCH2), 2.58 (s, 6H, 2CH3), 1.97
(m, 4H, 2SCH2CH2)
----
287 (M+, 27), 212 (22), 172 (48),
132 (48), 115 (52), 91 (100), 65 (80)
----
572 (M+, 17), 484 (3), 332 (11), 300 (36),
188 (22), 170 (100), 91 (30)
3041, 1623, 1278,
1070, 970
572 (M+, 26), 445 (37), 314 (100),
226 (30), 158 (45), 156 (76), 77 (42)
9b
3038, 1623, 1270,
1070, 973
7.51~7.49 (s, 8H, ArH), 3.39~3.31
(m, 4H, 2S CH2), 2.56, 2.43, 1.97 (m, 4H,
2SCH2CH2)
12.22 (s, 1H, NH), 8.58 (s, 1H, CH),
7.80~7.46 (m, 9H, ArH), 2.57 (s, 3H, CH3)
12.20 (s, 1H, NH), 8.57 (s, 1H, CH),
7.79~7.50 (m, 8H, ArH), 2.55, 2.43 (2s, 6H,
2CH3)
----
10a
10b
3297, 1674, 1574,
1287, 966
3317, 1680, 1595,
1277, 979
339 (M+, 82), 337 (93), 309 (100),
280 (52), 138 (77), 111 (34), 77 (55)
353 (M+, 19), 323 (100), 294 (29),
172 (29), 141 (13), 139 (29), 91 (5)
11a
11b
3297, 1674, 1575,
1282, 1069, 965
3332, 1687, 1578,
1273, 1067, 981
8.24 (s, 1H, CH), 7.84~7.36 (m, 9H, ArH),
2.67, 2.50 (2s, 6H, 2CH3)
8.24 (s, 1H, CH), 7.83~7.39 (m, 8H, ArH),
2.65, 2.55, 2.43 (3s, 9H, 3CH3)
----
395 (M+, 21), 353 (100), 268 (32),
216 (52), 172 (83), 144 (62), 91 (42)
Scheme II
The crystal 0.42*0.38*0.38 mm was mounted with graphic
monochromated MoK ( = 0.71073 Å), and data was col-
lected in the range 1.97º - 25.00º. Details of the intensity col-
lection are given in Table 3.
Compounds 2-11 were screened for their antibacterial
activities against E. coli, P. Aeruginosa, B. Subtilis and S.
aureus employing the cup-plate method at the concentration
Ortep 3 scheme of compound 3a

372 J. Chin. Chem. Soc., Vol. 49, No. 3, 2002
Table 3. X-ray Crystallography Data of 3a
Zhang et al.
pounds 2-3a, 7a-b, 8-9b and 11a-b express significant anti-
bacterial activity. The investigation on the structure-activity
relationship shows that a thiadiazole ring enhances the anti-
bacterial action of most of the title compounds.
Chemical formula
C18H15N5OS
M
349.41
Crystal system
Triclinic
Space group
P1
a (Å)
b (Å)
c (Å)
(º)
8.3530 (10)
10.331 (2)
10.843 (2)
97.99 (2)
EXPERIMENTAL
All reagents of laboratory grade were used without pu-
rification. The melting points are uncorrected and were taken
on an X-4 microscopic melting point apparatus. IR spectra
were recorded on a Nicolet AVATAR 360 FT-IR spectrometer
in KBr disc. 1H NMR was recorded on a Bruker AC-80 instru-
ment in DMSO-d6 with TMS as internal standard. Mass spec-
tra were performed on a ZAB-HS (EI) and VG ZAB-HS
(FAB) instruments. And the elemental analysis was per-
formed on an Elementar Vario EL apparatus.
(º)
101.610 (10)
111.170 (10)
831.4 (2)
364
2
(º)
V (Å3)
F (000)
Z
Dc (g. cm-3)
Reflections collected
Independent reflections
T (K)
Final R indics [I > 2ó (I)]
R indics
1.396
3221
2896 (Rint = 0.0103)
293 (2)
R1: 0.0343, wR2: 0.0842
R1: 0.0467, wR2: 0.0882
0.029 (3)
Extinction cofficient
Compound 1-aryl-5-methyl-1,2,3-triazol-4-form
hydrazide (1) was prepared from aryl amine by five
steps according to the literature15
Largest diff. Peak and hole (eÅ-3)
0.191 and -0.204
of 100 g/mL in the nutrient agar media (41 g nutrient agar/
1000 mL water).14 The investigation results are listed in Ta-
ble 4. The results showed that all compounds were active ex-
cept for 4b, 5a and 8-9a. It is worthwhile to note that com-
Preparation of 2-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-5-
mercapto-1,3,4-oxadiazoles (2)
To an ethanol (100 mL) solution of KOH (75 mmol),
hydrazide 1 (50 mmol) and carbon disulfide (100 mmol) were
added and the mixture was refluxed for 36 h. It was concen-
trated to a small volume, poured into ice water and filtered.
The filtrate on acidification gave a percipitate which was col-
lected and recrystallized from ethanol.
Table 4. Inhibition Effect of Compounds 2-11
No.
E. coli
P. aeruginosa B. subtilis
S. aureus
2a
2b
3a
3b
4a
++
+
++
++
+
+++
+
++
+++
-
++
+
+
-
+
+
++
+
+
+
General preparation of 2-(1-aryl-5-methyl-1,2,3-triazol-
4-yl)-5-alkylthio-1,3,4-oxadiazoles (3)-(5)
A mixture of thione 2 (1 mmol), sodium hydroxide (1
mmol for 3-4, 2 mmol for 5) and the appropriate halide (1
mmol) was stirred in 25 mL of water ( -bromo- -acetophe-
none was dissolved in 5 mL of ethanol and then added drop-
wise). Compound 3 was formed after stirring for 8 h at room
temperature, but 4-5 were successfully synthesized by
refluxing for only 4 h. The resulting thioether (5 appeared af-
ter being neutralized by 1N HCl) was collected by filtration,
washed with water and recrystallized from a suitable solvent.
4b
5a
5b
6a
6b
7a
7b
8a
++
+++
+++
++
++
++
+
-
++
-
++
-
++
++
+
-
-
-
-
+
+
-
-
++
+
+
++
+
++
+++
+
++
++
-
++
++
+++
+
+++
-
-
++
++
+
++
++
++
+
++
++
++
8b
9a
++
-
9b
10a
10b
11a
11b
++
++
+++
++
++
Preparation of 5-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-3-N-
p-methylphenylaminomethyl-1,3,4-oxadiazolin-5-thiones
(6)
+
+
A solution of 2 (1 mmol) in ethanol containing formal-
dehyde (0.15 mL) was stirred for 0.5 h under cooling by
ice-water bath. p-Toluidine (1 mmol) was added and the reac-
Zone diameter of growth inhibition: < 10 mm (-), 10-13 mm (+)
and 14-17 mm (++). Diameter of the cup = 8 mm.

2-(1-Aryl-5-methyl-1,2,3-triazol-4-yl)-1,3,4-oxadiazole
J. Chin. Chem. Soc., Vol. 49, No. 3, 2002 373
tion mixture was stirred for 8 h at room temperature. The ex-
cessive EtOH was removed and the resulting solid was
washed with petroleum (5 mL) and recrystallized from etha-
nol to yield 6.
Received December 3, 2001.
Key Words
1,2,3-Triazole; 1,3,4-Oxadiazole; X-ray
crystallography; Antibacterial test.
Synthesis of 2-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-5-
methylthio-1,3,4-oxadiazoles (7)
Dimethylsulfate (0.06 mmol) was added dropwise to
the mixture of 2 (1 mmol) and sodium hydraoxide (1 mmol)
and stirred overnight at room temperature to pricipate a white
solid. The crude product was collected by filtration, washed
with water and recrystallized from ethyl acetate-petroleum to
get 7.
REFERENCES
1. (a) Naito, K.; Watanabe, Y.; Egusa, S. Jpn. J. Appl. Phys.
Part 1 1999, 38(5A), 2792. (b) Xu, Z. M.; Li, G. W.; Ma, Y.
G.; Wu, F.; Tian, W. J.; Shen, J. C. J. Chin. Univ. Chem.
2000, 21(11), 1719.
2. (a) Eissa, A. A. H. Bull. Fac. Pharm. 1998, 36(3), 99. (b)
Holla, B. S.; Gonsalves, R.; Shenoy, S. Eur. J. Med. Chem.
2000, 35(2), 267. (c) Tinperciuc, B.; Parvu, A.; Palage, M.;
Oniga, O.; Ghiran, D. Farmacia (Bucharest) 1999, 47(5),
77.
General preparation of 1,2/1,4-bis[2-(1-aryl-5-methyl-
1,2,3-triazol-4-yl)-1,3,4-oxadiazolin-5-thio]ethanane/
butanane (8)-(9)
Appropriate 1,2-dichloroethanane/1,4-dibromobutane
(1/2 mmol) was added dropwise to the solution of 2 (1 mmol)
and equivalent NaOH in 30 mL of water and stirred for 0.5 h.
Then the mixture was refluxed for 2 h. The precipitation was
purified as 3-4 and 7 to get 8-9.
3. Al-Talib, M.; Orabi, S. A.; Al-Majdalawi, S.; Tashtoush, H.
India J. Heterocycl. Chem. 1999, 8(3), 183.
4. Tashtoush, H.; Abu-orabi, S.; Ta’an, E.; Al-Talib, M. Asian
J. Chem. 1999, 11(2), 444.
5. Milcent, M.; Barbier, G. J. Heterocycl. Chem. 1983, 20, 77.
6. Nassr, A. M.; Mahmoud, D. Org. Prep. Proced. Int. 1983,
15(5), 329.
Synthesis of 3-N-acetyl-5-(1-aryl-5-methyl-1,2,3-triazol-
4-yl)-2-p-chlorophenyl- 2-1,3,4-oxadiazoline (11)
7. Werber, G.; Buccheri, F.; et al. J. Heterocycl. Chem. 1978,
15(8), 1537.
A solution of 2 (2 mmol), equivalent p-chlorophenyl-
aldehyde was refluxed in 20 mL of ethanol for 4 h catalyzed
by p-toluene sulfonic acid. Intermediate p-chlorophenyl-
aldehyde-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-formhydrazo
ne 10 was precipitated in high yield. It was collected, dried
and refluxed in anhydrous acetic acid (5 mL) for 2 h. After re-
moval of excessive solvent, the residue was poured into
crushed ice to get a white powder. The crude product was
recrystallized from ethanol-ethyl acetate to afford 11.
8. Liu, F. M.; Yu, J. X.; Wang, W.; Liu, G.; Liu, Y. T.; Chen, Y.
Z. Youji Huaxue 1999, 19, 316.
9. Shama, R. S.; Bahel, S. C. Bakin Bobai 1982, 10(7), 293.
10. Chen, H. S.; Li, Z. M.; Wang, Z. W. Hecheng Huaxue 1999,
7(2), 164.
11. Dong, H. S.; Wei, K.; Wang, Q. L.; Quan, B. J. Chin. Chem.
Soc. 2000, 47, 541.
12. Liu, F. M.; Yu, J. X.; Lu, W. J.; Liu, G.; et al. Chin. J. Chem.
1999, 17(1), 62.
13. Chu, C. H.; Sun, X. W.; Sun, L.; Zhang, Z. Y.; et al. J. Chin.
Chem. Soc. 1999, 46, 229.
14. Xu, S. Y.; Bian, R. L.; Chen, X. Methodology of Pharmacol-
ogy Experiments; People’s Sanitation Publishing Company:
Beijing, 1994, 1356.
ACKNOWLEDGEMENT
We wish to thank the National Natural Science Founda-
tion (QT Program) of the PRC for its financial support.
15. El-khadem, H.; Mansour, H. A. R.; Meshreki, M. H. J.
Chem. Soc. (C) 1968, 1329.