Design and synthesis of diheterocyclic compounds containing tetrazolinone and 1,2,4-triazole

Article abstract of DOI:10.1002/jhet.5570440433

(Chemical Equation Presented) A novel series of 1-(4-chlorophenyl)-4-{[5- (alkylthio)-4-phenyl-4H-1,2,4-triazol-3-yl]methyl}-1,4-dihydro-5H-tetrazol-5- ones 6a-y were synthesized in good to excellent yields and their structures were identified by ¹

Full text of DOI:10.1002/jhet.5570440433

Jul-Aug 2007
937
Design and Synthesis of Diheterocyclic Compounds Containing
Tetrazolinone and 1,2,4-triazole
Yan-Ping Luo, Long Lin, Guang-Fu Yang*
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry,
Central China Normal University, Wuhan 430079, P. R. China
E-mail: gfyang@mail.ccnu.edu.cn
Received June 26, 2006
O
O
O
BrCH2CO2Et
NH2NH2.H2O
NHNH2
OEt
Cl
N
N
Cl
N
N
NH
N
N
N
Cl
N
N
N
N
O
O
2
3
1
PhNCS
O
O
O
Ph
N
Ph
N
5% Na2CO3
K2CO3,RX
DMF
NHNHCSNHPh
SR
SH
Cl
N
Cl
N
N
Cl
N
N
N
N
N
N
N
N
O
N
N
N
N
N
6
5
4
A novel series of 1-(4-chlorophenyl)-4-{[5-(alkylthio)-4-phenyl-4H-1,2,4-triazol-3-yl]methyl}-1,4-
dihydro-5H-tetrazol-5-ones 6a-y were synthesized in good to excellent yields and their structures were
1
identified by H nmr, 13C nmr, ms and elemental analysis. Determining the X-ray crystallography of
compound 6j indicated that there were strong intermolecular hydrogen bonds in the stacking interactions.
The bioassay results showed that compound 6k exhibited good insecticidal activities against T
cinnabarinus at the dosage of 250 mg.L-1. To our knowledge, this is the first report about the insecticidal
activity of tetrazolinone derivatives.
J. Heterocyclic Chem., 44, 937 (2007).
Keep in mind that 1,2,4-triazole derivatives also
exhibited various biological activities [2-8], and it is
possible to improve the herbicidal activity of tetrazol-
inones if 1,2,4-triazole moiety is introduced into the tetra-
zolinone scaffold. Therefore, a series of the title
compounds, 1-(4-chlorophenyl)-4-{[5-(alkylthio)-4-phenyl-
4H-1,2,4-triazol-3-yl]methyl}-1,4-dihydro-5H-tetrazol-5-
ones 6 were designed and synthesized (Scheme 2).
INTRODUCTION
Nitrogen-containing heterocyclic compounds have
displayed a broad spectrum of biological activities.
Within the synthesis of heterocyclic nitrogen-containing
compounds,
tetrazolinones
attracted
considerable
attention due to their excellent herbicidal activity [1]. For
example, 1-Aryl-4-substituted-1,4-dihydro-5H-tetrazol-5-
ones (Scheme 1) were reported to be a new class of
protoporphyrinogen oxidase inhibitor, whose weed
spectrum and crop selectivity could be dramatically
modified through manipulation of the substituent groups.
The compound (Y, M = H; Z = Cl; R = CH2CH=CH2)
showed 90% pre-emergence control of velvetleaf at 8000
g ai/ha. Such high application dosage motivated us to
improve the herbicidal activity by modifying the R group.
RESULTS AND DISCUSSION
Synthesis. Using an experimental procedure as
described in the literature [9], the starting material, 4-
chlorophenylisocyanate reacted with sodium azide in N,N-
dimethylformamide (DMF) to afford 1-(4-chlorophenyl)-
1,4-dihydro-5H-tetrazol-5-one (1) (75%). Treatment of
the tetrazolinone 1 with ethyl 2-bromoacetate in DMF
gave compound (2) in good yields. Refluxing compound 2
with hydrazine hydrate in ethanol for 4 hours afforded 2-
[4-(4-chlorophenyl)-5-oxo-4,5-dihydro-5H-tetrazol-1-yl]
acetohydrazide (3). According to reference [10-11], the
reaction of compound 3 with phenyl isothiocyanate in
ethanol yielded novel 2-{2-[4-(4-chlorophenyl)-5-oxo-
4,5-dihydro-5H-tetrazol-1-yl]acetyl}-N-phenylhydrazine
carbothioamide (4). Refluxing the thiosemicarbazide 4 in
5% aqueous sodium carbonate solution gave 1-(4-
Scheme 1
Y
O
z
N
N
N
N
R
M
General structure of herbicidal tetrazolinones

938
Y.-P. Luo, L. Lin, G.-F. Yang
Vol 44
Scheme 1
O
O
O
BrCH2CO2Et
NH2NH2.H2O
NHNH2
OEt
Cl
N
N
Cl
N
N
NH
N
N
N
Cl
N
N
N
N
O
O
2
3
1
PhNCS
O
O
O
Ph
N
Ph
N
5% Na2CO3
K2CO3,RX
DMF
NHNHCSNHPh
SR
SH
Cl
N
Cl
N
N
Cl
N
N
N
N
N
N
N
N
O
N
N
N
N
N
6
5
4
chlorophenyl)-4-[(5-mercapto-4-phenyl-4H- 1,2,4-triazol-
3-yl)methyl]-1,4-dihydro-5H-tetrazol-5-one (5). Compound
5 reacted with alkyl halides or substituted benzyl halides
to yield the title compounds 6.
played a fundamental role in the three-dimensional
organization of the molecules in the solid state. An
intermolecular hydrogen bond between the N atom and
aromatic hydrogen is shown in Figure 2. The distance of
C (12)…N (6) is 3.47 Å, and the angle of C (12)–H (12)–
N (6) is 165.10.
All compounds 6 gave satisfactory elemental analyses
and spectroscopic data (1H nmr, 13C nmr and ms) consistent
1
with their assigned structures. For example, in the H nmr
spectra, compounds 6 revealed a singlet at ꢀ 5.21-5.26 ppm,
which is attributed to the methylene between tetrazolinone
and 1,2,4-triazole, a multiplet in the region ꢀ 6.75–8.02
attributed to the aromatic protons; in the 13C nmr spectra,
C=O of tetrazol-5-one resonance was observed at ꢀ 147.58-
147.83 ppm, and two peaks in the region ꢀ 149.1-154.5ppm
are attributed to 1,2,4-triazole. The ms spectra revealed that
the molecular ion peaks and fragmentation peaks were in
accordance with the synthesized structures of the title
compound 6, the molecular ion peak was observed for all
the title compounds.
The single-crystal structure of 6j was determined by X-
ray crystallography as shown in Figure 1. The crystal
packing revealed intermolecular hydrogen bond, which
Figure 2. Chain of hydrogen-bonded molecules in crystal packing of
compound 6j.
Biological Activity. The biological activities of all
compounds were investigated. None of them was
proved to have significant herbicidal activities.
However, it is very fortunate for us to find some
compounds showing good insecticidal activity. For
example, as it is shown in Table 1 that compound 6k
gave a mortality-level of 80.6% against Tetranychus
cinnabarnus at the dosage of 250 mg.L-1 in vivo. To our
knowledge, this is the first report about the insecticidal
activity of tetrazolinone derivatives. It should be
mentioned that it is very difficult to control T
cinnabarinus in China. Therefore, the tetrazolinone
scaffold might be identified as novel insecticidal lead
structure for pesticide development.
Figure 1. Crystal structure of compound 6j.

Jul-Aug 2007 Design and Synthesis of Diheterocyclic Compounds Containing Tetrazolinone and 1,2,4-triazole
939
chemical reagents were commercially available and were treated
with standard methods before use. Solvents were dried in a
routine way and redistilled.
CONCLUSION
In conclusion, we developed a facile and mild method
to synthesize a new series of 1-(4-chlorophenyl)-4-{[5-
(alkylthio)-4-phenyl-4H-1,2,4-triazol-3-yl]methyl}-1,4-
dihydro-5H-tetrazol-5-ones 6 in good yields. As it comes
out from their biological activitiy study, one of them
compound 6k showed good insecticidal activity at 250
mg.L-1 against Tetranychus cinnabarnus in vivo. Further
optimization and structure activity relationships of the
title compounds are well under way.
Ethyl 2-[4-(4-chlorophenyl)-5-oxo-4,5-dihydro-5H-tetra-
zol-1-yl] acetate (2). A mixture of 1-(4-chlorophenyl)-1,4-
dihydro-5H-tetrazol-5-one 1 (0.1 mol), ethyl 2-bromoacetate
(0.11 mol) and anhydrous potassium carbonated (0.2 mol) in
DMF (25 mL) was stirred for 6 hours at room temperature,
according to thin layer chromatographic (TLC) analysis. And
then ice water was added to the reaction mixture to form
precipitate, which was collected by filtration, washed with
water, dried and recrystallized from ethanol to obtain compound
Table 1
The results of insecticidal activities of compounds 6
Com.
R
250 mg.L-1
500 mg.L-1
T. cinnabarnus
0.0
A. medicagini
7.1
N. legen
0.0
3.3
0.0
6.7
3.3
6.7
0.0
3.3
M. separata
0.0
6a
6b
6c
6d
6e
6f
6g
6h
6i
CH3
C2H5
C3C7
0.0
2.9
0.0
1.4
21.4
2.9
0.0
10.0
0.0
2.9
4.3
0.0
0.0
1.4
5.7
0.0
0.0
60.0
0.0
0.0
6.7
0.0
0.0
CH2=CHCH2
C4H9
CH2CO2C2H5
CH(CH3)CO2C2H5
C6H13
C8H17
0.0
3.3
6j
6k
6l
6m
6n
6o
6p
6q
6r
6s
6t
6u
6v
6w
C6H5CH2
1.4
80.6
2.9
2.9
0.0
1.4
8.6
2.9
0.0
1.4
5.7
0.0
0.0
0.0
1.4
1.4
1.4
2.9
0.0
0.0
0.0
0.0
4.3
5.7
0.0
1.4
2.9
6.7
3.3
0.0
3.3
0.0
0.0
0.0
3.3
3.3
0.0
20.0
13.3
6.7
20.0
37.5
0.0
0.0
64.7
6.7
15.0
0.0
0.0
0.0
40.0
0.0
3-CH3-C6H4CH2
4-CH3-C6H4CH2
3-Br-C6H4CH2
4-Br-C6H4CH2
2-Cl-C6H4CH2
3-Cl-C6H4CH2
4-Cl-C6H4CH2
3-F-C6H4CH2
3,4-F2-C6H3CH2
2,4-F2-C6H3CH2
2,6-F2-C6H3CH2
2-Br-4-F-C6H3CH2
2-NO2-5-CH3-C6H3CH2
33.3
0.0
0.0
0.0
H3CO2C
NOCH3
CH2
6x
0.0
1.4
0.0
10.0
0.0
H3CO2C
OCH3
CH2
6y
4.3
0.0
0.0
Dichlorvos
Pyridabea
-
-
-
100.0
-
100.0
-
100.0
The application concentration of Dichlorvos and Pyridaben were 500 mg.L-1 and 50 mg.L-1, respectively.
2 as colorless needles; yield: 90%, mp 115-116º; 1H nmr
(deuteriochloroform): ꢀ 1.32 (t, 3H, J = 7.2Hz, CH3), 4.30 (q,
2H, J = 7.2Hz, CH2), 4.81 (s, 2H, CH2), 7.47 (dd, 4H, J = 8.4Hz,
ArH); ms: m/z 282 (M+, 2), 155 (29), 153 (100), 125 (18). Anal.
Calcd. for C11H11ClN4O3: C, 46.74; H, 3.92; N, 19.82. Found: C,
46.72; H, 3.95; N, 19.43.
EXPERIMENTAL
Melting points were uncorrected and determined with Electro
thermal digital melting point apparatus, and ms spectra were
determined using
a Finnig an Trace MS organic mass
spectrometer, and signals were given in m/z. 1H nmr and 13C nmr
were recorded in deuteriochloroform or dimethylsulfoxide on a
Varian Mercury 400 spectrometer and resonances are given in
ppm (ꢀ) relative to TMS. Elementary analyses (EA) were
performed on a Vario EL III elementary analysis instrument. All
2-[4-(4-Chlorophenyl)-5-oxo-4,5-dihydro-5H-tetrazol-1-yl]
acetohydrazide (3). Hydrazine hydrate (0.5 mol) was added to a
solution of ethyl 2-[2-(4-chlorophenyl)-5-oxo-4,5-dihydro-5H-
tetrazol-1-yl]acetate (2) (0.1 mol) in ethanol (100 mL). The
reaction mixture was heated under reflux for
4 hours,

940
Y.-P. Luo, L. Lin, G.-F. Yang
Vol 44
concentrated in vacuum, cooled and diluted with water. The
obtained precipitate was collected by filtration, washed with ice
water, dried and recrystallized from ethanol. Yield: 88%; mp
235-237º; 1H nmr (dimethylsulfoxide-d6): ꢀ 4.39 (s, 2H, NH2),
4.69 (s, 2H, CH2), 7.66 (dd, 4H, J = 8.8Hz, ArH), 9.47 (s, 1H,
NH); ms: m/z 268 (M+, 10), 181 (10), 155 (31), 153 (100), 127
(10), 125 (27), 115 (16). Anal. Calcd. for C9H9ClN6O2: C, 40.24;
H, 3.38; N, 31.28. Found: C, 40.23; H, 3.27; N, 30.95.
1-(4-Chlorophenyl)-4-[(4-phenyl-5-propylthio-4H-1,2,4-tria-
zol-3-yl)methyl]-1,4-dihydro-5H-tetrazol-5-one (6c). Colorless
needles, yield 96%; mp 100-102º; 1H nmr (deuteriochloroform): ꢀ
1.00 (t, 3H, J = 7.2Hz, CH3), 1.75-1.80 (m, 2H, CH2), 3.23 (t, 2H,
J = 7.2Hz, SCH2), 5.24 (s, 2H, CH2), 7.25-7.77 (m, 9H, ArH); 13
C
nmr (100 MHz, deuteriochloroform): ꢀ 13.16, 22.60, 34.28, 39.33,
120.17, 126.81, 129.46, 130.09, 130.49, 132.05, 132.68, 133.39,
147.77, 148.80, 153.89; ms: m/z 428 (M+, 13), 388 (32), 385
(100), 380 (52), 231 (50), 203 (20), 153 (19), 125 (11). Anal.
Calcd. for C19H18ClN7OS: C, 53.33; H, 4.24; N, 22.91; S, 7.49.
Found: C, 53.02; H, 4.00; N, 22.65; S, 7.78.
2-{2-[4-(4-Chlorophenyl)-5-oxo-4,5-dihydro-5H-tetrazol-1-
yl]acetyl}-N-phenylhydrazinecarbothioamide (4). A solution
containing 2-[4-(4-chlorophenyl)-5-oxo-4,5-dihydro-5H-tetra-
zol-1-yl] acetohydrazide (3) (0.01 mol) and phenyl isothio-
cyanate (0.01 mol) in ethanol (20 mL) was heated under reflux
for 4 hours and then cooled at room temperature. The obtained
precipitate was collected by filtration, washed with water, dried,
yield: 99%, mp 212-214º; this compound (4) was not
recrystallized or identified, but was used directly in next step.
1-(4-Chlorophenyl)-4-(5-mercapto-4-phenyl-4H-1,2,4-tria-
zol-3-yl)methyl-1,4-dihydro-5H-tetrazol-5-one (5). A stirring
mixture of thiosemicarbazide (4) (1 mmol) and 5% aqueous
sodium carbonate solution (10 mL) was refluxed for 5 hours.
The reaction mixture was cooled, and then adjusted to pH 6 with
10% hydrochloric acid. The formed precipitate was collected by
filtration, washed with water, dried and recrystallized from a
mixture solution of DMF and water. Yield 95%; mp 248-250º;
1H nmr (dimethylsulfoxide-d6): ꢀ 5.06 (s, 2H, CH2), 7.20 (m,
9H, ArH), 14.26 (s, 1H, SH); ms: m/z 386 (M+, 22), 248 (15),
153 (20), 125 (48), 111(19), 90 (64), 63 (100). Anal. Calcd. for
C16H12ClN7OS: C, 49.81; H, 3.13; N, 25.41; S, 8.31. Found: C,
49.68; H, 2.95; N, 25.30; S, 8.12.
1-[(5-Allylthio-4-phenyl-4H-1,2,4-triazol-3-yl)methyl]-4-(4-
chlorophenyl)-1,4-dihydro-5H-tetrazol-5-one (6d). Colorless
1
needles, yield 95%; mp 138-140º; H nmr (deuteriochloroform):
ꢀ 3.86 (d, 2H, J = 7.2Hz, SCH2), 5.26 (s, 2H, CH2), 5.13-5.30
(m, 2H, CH2), 5.90-5.97 (m, 1H, CH), 7.24-7.79 (m, 9H, ArH);
13C nmr (100 MHz, deuteriochloroform): ꢀ 35.28, 39.36, 119.22,
120.20, 126.87, 129.50, 130.12, 130.57, 131.98, 132.20, 132.70,
133.45, 147.81, 149.01, 153.03; ms: m/z 425.5 (M+, 100), 427.5
(M++2, 85), 410 (74), 272 (18), 257 (24), 153 (29), 125 (22).
Anal. Calcd. for C19H16ClN7OS: C, 53.58; H, 3.79; N, 23.02; S,
7.53. Found: C, 53.39; H, 3.49; N, 22.80; S, 7.63.
1-[(5-Butylthio-4-phenyl-4H-1,2,4-triazol-3-yl)methyl]-4-
(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-5-one (6e). Colorless
needles, yield 64ꢀ; mp 104-106º; 1H nmr (deuteriochloroform): ꢀ
0.91 (t, 3H, J = 7.2Hz, CH3), 1.38-1.74 (m, 4H, CH2), 3.25 (t, 2H,
J = 7.2Hz, SCH2), 5.24 (s, 2H, CH2), 7.25-7.77 (m, 9H, ArH); 13
C
nmr (100 MHz, deuteriochloroform): ꢀ 13.47, 21.71, 31.08, 32.00,
39.28, 120.14, 126.76, 129.47, 130.11, 130.52, 131.94, 132.61,
133.37, 147.73, 148.79, 153.99; ms: m/z 443 (M++1, 47), 395
(88), 386 (19), 241 (11), 153 (100), 125 (58), 90 (46). Anal. Calcd.
for C20H20ClN7OS: C, 54.35; H, 4.56; N, 22.19; S, 7.26. Found: C,
54.07; H, 4.27; N, 21.96; S, 7.48.
General Procedure for the preparation of 1-(4-
chlorophenyl)-4-{[5-(alkylthio)-4-phenyl-4H-1,2,4-triazol-3-
yl]methyl}-1,4-dihydro-5H-tetrazol-5-one (6). To stirring
solution of the mercaptotriazole (5) (1 mmol) in DMF (5 mL),
the appropriate alkyl halide or substituted benzyl halide (1.1
mmol) and anhydrous potassium carbonate (2 mmol) were
added gradually. The reaction mixture was stirred at room
temperature for 6-8 hours, according to TLC. At the end of this
duration, the reaction mixture was poured into ice water. The
precipitate was collected by filtration, washed with water, dried
and recrystallized from ethanol.
1-(4-Chlorophenyl)-4-{[5-( ꢁ-acetate ethyl)thio-4-phenyl-
4H-1,2,4-triazol-3-yl]methyl}-1,4-dihydro-5H-tetrazol-5-one
(6f). Colorless needles, yield 79°; mp 110-112º; 1H nmr
(deuteriochloroform): ꢀ 1.27 (t, 3H, J = 7.2Hz, CH3), 4.08 (s,
2H, SCH2), 4.20 (q, 2H, J = 7.2Hz, CH2), 5.24 (s, 2H, CH2),
7.26-7.78 (m, 9H, ArH); 13C nmr (100 MHz, deuteriochloro-
form): ꢀ 14.02, 34.42, 39.25, 62.09, 120.19, 126.80, 129.49,
130.22, 130.71, 131.72, 132.69, 133.44, 147.79, 149.22, 152.34,
167.94; ms: m/z 472 (M+, 62), 426 (22), 398 (22), 153 (100),
124.9 (59), 111 (15), 90 (37). Anal. Calcd. for C20H18ClN7O3S:
C, 50.90; H, 3.84; N, 20.78; S, 6.79. Found: C, 50.96; H, 3.54;
N, 20.60; S, 6.88.
1-(4-Chlorophenyl)-4-{[5-(2-ethoxy-1-methyl-2-oxoethyl)-
thio-4-phenyl-4H-1,2,4-triazol-3-yl]methyl}-1,4-dihydro-5H-
tetrazol-5-one (6g). Colorless needles, yield 95°; mp 108-110º;
1H nmr (deuteriochloroform): ꢀ 1.24 (t, 3H, J = 7.2Hz,
CH2CH3), 1.62 (d, 3H, CHCH3), 4.16 (q, 1H, J = 7.2Hz, CH),
4.50 (q, 2H, J = 7.2Hz, SCH2), 5.24 (s, 2H, CH2), 7.26-7.78 (m,
9H, ArH); 13C nmr (100 MHz, deuteriochloroform): ꢀ 13.95,
18.17, 39.32, 44.62, 61.83, 120.17, 126.85, 129.47, 130.12,
130.61, 131.82, 132.68, 133.41, 147.77, 149.13, 151.82, 171.20;
ms: m/z 486 (M+, 60), 441 (41), 413 (70), 386 (58), 153 (100),
125 (61), 118 (20), 90 (38) Anal. Calcd. for C21H20ClN7OS: C,
51.90; H, 4.15; N, 20.18; S, 6.60. Found: C, 52.06; H, 3.87; N,
20.08; S, 6.68.
1-(4-Chlorophenyl)-4-[(5-methylthio-4-phenyl-4H-1,2,4-tria-
zol-3-yl)methyl]-1,4-dihydro-5H-tetrazol-5-one (6a). Colorless
needles, yield 96%; mp 175-177º; 1H nmr (deuteriochloroform): ꢀ
2.72 (s, 3H, SCH3), 5.25 (s, 2H, CH2), 7.26-7.76 (m, 9H, ArH);
13C nmr (100 MHz, deuteriochloroform): ꢀ 14.44, 39.27, 120.17,
126.73, 129.46, 130.15, 130.57, 131.89, 132.66, 133.40, 147.75,
149.00, 154.45; ms: m/z 400 (M+, 76), 153 (100), 125 (79). Anal.
Calcd. for C17H14ClN7OS: C, 51.06; H, 3.53; N, 24.52; S, 8.02.
Found: C, 51.12; H, 3.31; N, 24.29; S, 8.22.
1-(4-Chlorophenyl)-4-[(5-ethylthio-4-phenyl-4H-1,2,4-
triazol-3-yl)methyl]-1,4-dihydro-5H-tetrazol-5-one (6b).
1
Colorless needles, yield 98%; mp 152-153º; H nmr (deuterio-
chloroform): ꢀ 1.41 (t, 3H, J = 7.2Hz, CH3), 3.25 (q, 2H, J =
7.2Hz, SCH2), 5.24 (s, 2H, CH2), 7.25-7.77 (m, 9H, ArH); 13C
nmr (100 MHz, deuteriochloroform): ꢀ 14.61, 26.75, 39.32,
120.14, 126.80, 129.43, 130.06, 130.47, 132.01, 132.66,
133.31, 147.74, 148.84, 153.89; ms: m/z 413.4 (M+, 65),
385.3 (40.17), 279 (100), 309 (37), 260 (61), 233 (28), 231
(36), 218 (29), 153 (26), 125 (19). Anal. Calcd. for
C18H16ClN7OS: C, 52.24; H, 3.90; N, 23.69; S, 7.75. Found:
C, 52.15; H, 3.60; N, 23.50; S, 7.90.
1-(4-Chlorophenyl)-4-[(5-hexylthio-4-phenyl-4H-1,2,4-tria-
zol-3-yl)methyl]-1,4-dihydro-5H-tetrazol-5-one (6h). Colorless
1
needles, yield 67%; mp 119-121º; H nmr (deuteriochloroform):
ꢀ 0.86 (t, 3H, J = 7.2Hz, CH3), 1.25-1.75 (m, 8H, CH2), 3.23 (t,

Jul-Aug 2007 Design and Synthesis of Diheterocyclic Compounds Containing Tetrazolinone and 1,2,4-triazole
941
2H, J = 7.2Hz, SCH2), 5.23 (s, 2H, CH2), 7.24-7.77 (m, 9H,
ArH); 13C nmr (100 MHz, deuteriochloroform): ꢀ 13.95, 22.43,
28.28, 29.14, 31.16, 32.15, 39.37, 120.22, 126.85, 129.51,
130.13, 130.52, 132.11, 132.74, 133.46, 147.83, 148.81, 154.02;
ms: m/z 470 (M+, 23), 423 (98), 386 (43), 153 (100), 125 (58),
111 (18), 90 (37). Anal. Calcd. for C22H24ClN7OS: C, 56.22; H,
5.15; N, 20.86; S, 6.82. Found: C, 56.18; H, 4.81; N, 20.86; S,
6.82.
(M++2, 31), 474 (36), 385 (39), 170.9 (18). Anal. Calcd. for
C23H17BrClN7OS: C, 49.79; H, 3.09; N, 17.67; S, 5.78. Found:
C, 49.48; H, 2.77; N, 17.51; S, 5.82.
1-{[5-(4-Bromo-benzylthio)-4-phenyl-4H-1,2,4-triazol-3-
yl]methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-5-one
(6n). Colorless needles, yield 94%; mp 142-144º; 1H nmr
(deuteriochloroform): ꢀ 4.38 (s, 2H, SCH2), 5.22 (s, 2H, CH2),
7.07-7.78 (m, 13H, ArH); 13C nmr (100 MHz, deuteriochloro-
form): ꢀ 36.44, 39.36, 120.18, 121.71, 126.77, 129.51, 130.10,
130.58, 130.81, 131.71, 131.82, 132.72, 133.41, 135.52, 147.78,
149.17, 152.74; ms: m/z 555 (M+-1, 100), 558 (M++2, 31), 446
(37), 444 (28), 385 (49), 285 (15), 170 (46), 152 (23). Anal.
Calcd. For C23H17BrClN7OS: C, 49.79; H, 3.09, N, 17.67; S,
5.78. Found: C, 49.95; H, 2.82; N, 17.54; S, 5.88.
1-{[5-(2-Chloro-benzylthio)-4-phenyl-4H-1,2,4-triazol-3-yl]-
methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-5-one
(6o). Colorless needles, yield 94%; mp 135-136º; 1H nmr
(deuteriochloroform): ꢀ 4.56 (s, 2H, SCH2), 5.21 (s, 2H, CH2),
7.07-7.77 (m, 13H, ArH); 13C nmr (100 MHz, deuteriochloro-
form): ꢀ 34.86, 39.30, 120.12, 126.71, 126.92, 129.19, 129.43,
129.50, 129.99, 130.44, 131.41, 131.77, 132.65, 133.35, 134.20,
134.23, 147.72, 149.13, 152.99; ms: m/z 510 (M+, 2), 477 (51),
475 (100), 321 (64). Anal. Calcd. for C23H17Cl2N7OS: C, 54.12;
H, 3.36; N, 19.23; S, 6.28. Found: C, 54.12; H, 3.09; N, 19.30;
S, 6.39.
1-{[5-(3-Chloro-benzylthio)-4-phenyl-4H-1,2,4-triazol-3-yl]-
methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-5-one
(6p). Colorless needles, yield 99%; mp 139-140º; 1H nmr
(deuteriochloroform): ꢀ 4.40 (s, 2H, SCH2), 5.22 (s, 2H, CH2),
7.09-7.77 (m, 13H, ArH); 13C nmr (100 MHz, deuteriochloro-
form): ꢀ 36.46, 39.30, 120.17, 126.74, 127.29, 127.91, 129.09,
129.48, 129.82, 130.08, 130.58, 131.76, 132.68, 133.43, 134.31,
138.30, 147.76, 149.15, 152.71; ms: m/z 510 (M+, 55), 400 (16),
279 (100), 251 (21), 241 (20), 124.7 (22). Anal. Calcd. for
C23H17Cl2N7OS: C, 54.12; H, 3.36; N, 19.23; S, 6.28. Found: C,
54.00; H, 3.21; N, 18.94; S, 6.18.
1-{[5-(4-Chloro-benzylthio)-4-phenyl-4H-1,2,4-triazol-3-yl]-
methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-5-one
(6q). Colorless needles, yield 99%; mp 157-159º; 1H nmr
(deuteriochloroform): ꢀ 4.39 (s, 2H, SCH2), 5.22 (s, 2H, CH2),
7.08-7.78 (m, 13H, ArH); 13C nmr (100 MHz, deuteriochloro-
form): ꢀ 36.21, 39.24, 120.08, 126.64, 128.67, 129.44, 130.03,
130.43, 130.53, 131.64, 132.56, 133.33, 133.48, 134.83, 147.67,
149.12, 152.76; ms: m/z 510 (M+, 94), 400 (46), 279 (100), 355
(20), 312 (26), 247 (25), 241 (100), 153 (27), 125 (95). Anal.
Calcd. for C23H17Cl2N7OS: C, 54.12; H, 3.36; N, 19.23; S, 6.28.
Found: C, 54.40; H, 3.09; N, 18.96; S, 6.40.
1-(4-Chlorophenyl)-4-[(5-octylthio-4-phenyl-4H-1,2,4-tria-
zol-3-yl)methyl]-1,4-dihydro-5H-tetrazol-5-one (6i). Colorless
1
needles, yield 94%; mp 108-110º; H nmr (deuteriochloroform):
ꢀ 0.87 (t, 3H, J = 7.2Hz, CH3), 0.88-1.77 (m, 12H, 6 ꢁ CH2),
3.25 (t, 2H, J = 7.2Hz, SCH2), 5.24 (s, 2H, CH2), 7.25-7.77 (m,
9H, ArH); 13C nmr (100 MHz, deuteriochloroform): ꢀ 14.01,
22.54, 28.59, 28.93, 29.03, 29.15, 31.68, 32.44, 39.35, 120.18,
126.83, 129.48, 130.10, 130.50, 132.07, 132.71, 133.42, 147.79,
148.79, 153.96; ms: m/z 498 (M+, 99.6), 451 (100), 386 (78),
311 (22), 231 (88), 153 (58), 125 (32). Anal. Calcd. for
C24H28ClN7OS: C, 57.88; H, 5.67; N, 19.69; S, 6.44. Found: C,
57.74, H, 5.37; N, 19.64; S, 6.86.
1-[(5-Benzylthio-4-phenyl-4H-1,2,4-triazol-3-yl)methyl]-
4-(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-5-one (6j).
1
Colorless needles, yield 93°; mp 142-144º; H nmr (deuterio-
chloroform): ꢀ 4.44 (s, 2H, SCH2), 5.22 (s, 2H, CH2), 7.05-7.77
(m, 14H, ArH); 13C nmr (100 MHz, deuteriochloroform): ꢀ
37.11, 39.17, 120.01, 126.63, 127.60, 128.49, 128.96, 129.35,
129.89, 130.36, 131.66, 132.50, 133.21, 135.97, 147.58, 148.96,
153.00; Ms: m/z 475 (M+, 100), 477(M++2, 24), 385 (51), 366
(20), 124 (22), 89 (81), 61 (27). Anal. Calcd. for C23H18ClN7OS:
C, 58.04; H, 3.81; N, 20.60; S, 6.74. Found: C, 58.15; H, 3.51;
N, 20.80; S, 6.67.
1-(4-Chlorophenyl)-4-{[5-(3-methyl-benzylthio)-4-phenyl-
4H-1,2,4-triazol-3-yl]methyl}-1,4-dihydro-5H-tetrazol-5-one
(6k). Colorless needles, yield 93%; mp 166-168º; 1H nmr
(deuteriochloroform): ꢀ 2.28 (s, 3H, CH3), 4.45 (s, 2H, SCH2),
5.22 (s, 2H, CH2), 7.01-7.77 (m, 13H, ArH); 13C nmr (100 MHz,
deuteriochloroform): ꢀ 18.95, 35.77, 39.34, 120.17, 126.21,
126.79, 128.14, 129.49, 129.95, 130.08, 130.41, 130.50, 131.92,
132.69, 133.42, 133.69, 137.01, 147.75, 149.01, 153.22; ms: m/z
489 (M+, 100), 491 (M++1, 33), 492 (M++2, 36), 474 (25), 456
(46), 385 (15), 105 (30). Anal. Calcd. for C24H20ClN7OS: C,
58.83; H, 4.11; N, 20.01; S, 6.54. Found: C, 59.05; H, 3.92; N,
19.91; S, 6.60.
1-(4-Chlorophenyl)-4-{[5-(4-methyl-benzylthio)-4-phenyl-
4H-1,2,4-triazol-3-yl]methyl}-1,4-dihydro-5H-tetrazol-5-one
(6l). Colorless needles, yield 91%; mp 136-138º; 1H nmr
(deuteriochloroform): ꢀ 2.31 (s, 3H, CH3), 4.40 (s, 2H, CH2),
5.22 (s, 2H, CH2), 7.07-7.77 (m, 13H, ArH); 13C nmr (100 MHz,
deuteriochloroform): ꢀ 21.05, 37.04, 39.33, 120.15, 126.78,
128.97, 129.27, 129.47, 129.97, 130.42, 131.90, 132.69, 133.01,
133.40, 137.51, 147.74, 148.95, 153.29; ms: m/z 489 (M+, 100),
491 (M++1, 30), 492 (M++2, 36), 385 (34), 105 (34). Anal.
Calcd. for C24H20ClN7OS: C, 58.83; H, 4.11; N, 20.01; S, 6.54.
Found: C, 58.67; H, 3.81; N, 19.97; S, 6.75.
1-{[5-(3-Bromo-benzylthio)-4-phenyl-4H-1,2,4-triazol-3-
yl]methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-5-one
(6m). Colorless needles, yield 75%; mp 160-162º; 1H nmr
(deuteriochloroform): ꢀ 4.39 (s, 2H, SCH2), 5.23 (s, 2H, CH2),
7.09-7.77 (m, 13H, ArH); 13C nmr (100 MHz, deuteriochloro-
form): ꢀ 36.29, 39.20, 113.28, 120.09, 122.38, 126.66, 127.75,
129.43, 130.06, 130.55, 130.76, 131.61, 131.91, 132.56, 133.33,
138.49, 147.66, 149.14, 152.63; ms: m/z 555 (M+, 100), 557
1-{[5-(3-Fluoro-benzylthio)-4-phenyl-4H-1,2,4-triazol-3-yl]-
methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-5-one
(6r). Colorless needles, yield 89%; mp 158-160º; 1H nmr
(deuteriochloroform): ꢀ 4.42 (s, 2H, SCH2), 5.23 (s, 2H, CH2),
6.95-7.77 (m, 13H, ArH); 13C nmr (100 MHz, deuteriochloro-
form): ꢀ 36.46, 39.29, 114.59, 114.80, 115.86, 116.07, 120.16,
124.76, 126.73, 129.46, 130.06, 130.55, 131.78, 132.67, 133.04,
138.65, 138.72, 147.75, 149.14, 152.77, 161.47, 163.84; ms: m/z
493 (M+, 100), 495 (M++1, 25), 496 (M++2, 32), 384 (14), 108
(84). Anal. Calcd. for C23H17ClFN7OS: C, 55.93; H, 3.47; N,
19.85; S, 6.49. Found: C, 55.95; H, 3.22; N, 19.99; S, 6.23.
1-{[5-(3,4-Difluoro-benzylthio)-4-phenyl-4H-1,2,4-triazol-
3-yl]methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-5-
1
one (6s). Colorless needles, yield 67%; mp 165-167º; H nmr
(deuteriochloroform): ꢀ 4.39 (s, 2H, SCH2), 5.23 (s, 2H, CH2),

942
Y.-P. Luo, L. Lin, G.-F. Yang
Vol 44
7.05-7.78 (m, 12H, ArH); 13C nmr (100 MHz, deuteriochloro-
form): ꢀ 35.61, 39.20, 117.10, 117.27, 117.96, 118.13, 120.07,
125.24, 126.62, 129.42, 130.09, 130.62, 131.57, 132.54,
133.33, 147.68, 148.60, 148.74, 149.19, 151.08, 151.21,
152.57; ms: m/z 511 (M+, 100), 513 (M++1, 14), 514 (M++2,
42), 385 (48), 242 (25), 127 (63). Anal. Calcd. for
C23H16ClF2N7OS: C, 53.96; H, 3.15; N, 19.15; S, 6.26. Found:
C, 53.91; H, 2.85; N, 18.90; S, 6.37.
134.57, 147.71, 148.86, 149.06, 152.92, 162.99; ms: m/z 591
(M+, 31), 560 (88), 532 (67), 501 (42), 475 (69), 386 (31),
349 (29), 205 (58), 153 (80), 125 (44), 116 (100). Anal.
Calcd. for C27H23ClN8O4S: C, 54.87; H, 3.92; N, 18.96; S,
5.43. Found: C, 54.83; H, 3.75; N, 18.77; S, 5.50.
Methyl(2E)-(2-((5-((4-(4-chlorophenyl)-5-oxo-4,5-dihydro-
5H-tetrazol-1-yl)methyl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)-
methyl)phenyl)-3-methoxyacrylate (6y). Colorless needles,
1
1-{[5-(2,4-Difluoro-benzylthio)-4-phenyl-4H-1,2,4-triazol-
3-yl]methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-
yield 73%; mp 186-188º; H nmr (deuteriochloroform): ꢀ 3.59
(s, 3H, CO2CH3), 3.74 (s, 3H, OCH3), 4.38 (s, 2H, SCH2), 5.22
(s, 2H, CH2), 7.08-7.77 (m, 13H, ArH); 13C nmr (100 MHz,
deuteriochloroform): ꢀ 35.24, 39.25, 51.48, 61.64, 109.46,
120.13, 126.75, 127.66, 128.16, 129.41, 129.86, 130.01, 130.25,
131.11, 131.82, 132.57, 132.82, 133.29, 135.07, 147.67, 149.07,
153.69, 160.28, 167.59; ms: m/z 590 (M+, 7), 513 (17), 385 (14),
204 (32), 145 (100), 125 (13), 115 (19). Anal. Calcd. for
C28H24ClN7O4S: C, 56.99; H, 4.10; N,16.62; S, 5.43. Found: C,
57.00; H, 4.14; N, 16.36; S, 5.81.
1
5-one (6t). Colorless needles, yield 62%; mp 122-124º; H nmr
(deuteriochloroform): ꢀ 4.44 (s, 2H, SCH2), 5.23 (s, 2H, CH2),
6.75-7.78 (m, 12H, ArH); 13C nmr (100 MHz, deuterio-
chloroform): ꢀ 29.58, 39.34, 103.91, 104.16, 111.22, 111.43,
119.85, 120.18, 126.72, 129.51, 130.13, 130.61, 131.77, 132.21,
132.70, 133.47, 147.80, 149.22, 152.86; ms: m/z 511 (M+, 47),
514 (M++2, 13), 385 (5), 242 (8), 126 (100). Anal. Calcd. for
C23H16ClF2N7OS: C, 53.96; H, 3.15; N, 19.15; S, 6.26. Found: C,
53.86; H, 2.94; N, 19.11; S, 6.46.
Insecticidal Tests. The insecticidal activities against Aphis
medicagini, Nilaparvata legen, Mythima separata and
1-{[5-(2,6-Difluoro-benzylthio)-4-phenyl-4H-1,2,4-triazol-
3-yl]methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-tetrazol-5-
T
cinnabarinus of the title compounds were investigated using the
commercial products, Dichlorvos and Pyridabea. The insects
were reared in a room maintained at 25 (±1)º, 60 (±5)% relative
humidity, and 14 h light photoperiod. Stock solutions of each
test compound were prepared in DMF at a concentration of 1.0 g
litre-1, and then diluted to the required test concentrations with
water containing TW-80. Groups of 10 insects of each species
were transferred to glass Petri dishes and sprayed with test
solutions using a Potter sprayer. After air-drying, they were kept
in a room for normal cultivation. The mortality was determined
by the number and size of live larvae in the treated bottles
relative to that in the untreated controls in 72 h. In the case of
Nilaparvat lugen, rice seedlings (second semester) were dipped
in the test solution for 5 s, air-dried and then placed in a large
test tube. Each test rube contained 20 seedlings. Twenty insects
(fifth instar) were introduced into the tube, and the mouth of the
tube was covered with white cheesecloth. The tube was kept at
room temperature, and the number of live and dead insects
counted after 72 h. In a control experiment, carried out under the
same conditions, 1 mL of DMF was applied on each insect. All
experiments and the respective controls were carried out in three
replicates and percentage mortality was estimated with Abbott’s
formula [12]. The results of insecticidal activities were listed in
Table 1.
X-Ray Analysis of Compound 6j. The single crystal 6j was
obtained by evaporating the solvent. A crystal with dimensions
of 0.30 mm x 0.20 mm x 0.06 mm was mounted on a Bruker
SMART 1000 diffractmeter at 292(2) K with a graphite
monochromated MoKꢁ radiation (ꢂ = 0.71073 Å). The Crystal
data for 6j: C23H18ClN7OS; Triclinic, space group P-1, a =
8.6328(18), b = 10.083(2), c = 13.148(3) Å, ꢃ = 87.077(4)°, V =
1105.0(4) Å3, Z = 2, Dc = 1.431 mg/m3. A total of 5535
reflections were measured in the range of 1.56° ꢀ ꢄ ꢀ 25.00°, of
which 3832 (Rint = 0.0193) were independent and 2782 were
observed with I > 2ꢅ (I). The structure was solved by direct
methods and refined on F2 by full-matrix least-squares procedure
with Bruker SHELXTL-97 package [13].
1
one (6u). Colorless needles, yield 69%; mp 136-138º; H nmr
(deuteriochloroform): ꢀ 4.47 (s, 2H, SCH2), 5.26 (s, 2H, CH2),
6.84-7.77 (m, 12H, ArH); 13C nmr (100 MHz, deuteriochloro-
form): ꢀ 24.48, 39.38, 111.27, 111.51, 112.06, 120.22, 126.79,
129.51, 129.76, 130.10, 130.57, 131.92, 132.71, 133.47, 147.81,
149.31, 152.47, 160.08, 162.50; ms: m/z 511 (M+, 100), 514
(M++2, 41), 385 (32), 242 (23), 127 (63). Anal. Calcd. for
C23H16ClF2N7OS: C, 53.96; H, 3.15; N, 19.15; S, 6.26. Found: C,
54.07; H, 2.90; N, 19.33; S, 6.10.
1-{[5-(4-Bromo-2-fluorobenzylthio)-4-phenyl-4H-1,2,4-
triazol-3-yl]methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-
tetrazol-5-one (6v). Colorless needles, yield 64%; mp 136-137º;
1H nmr (deuteriochloroform): ꢀ 4.41 (s, 2H, SCH2), 5.23 (s, 2H,
CH2), 7.12-7.78 (m, 13H, ArH); 13C nmr (100 MHz, deuterio-
chloroform): ꢀ 29.68, 39.33, 118.95, 119.19, 120.17, 122.00,
122.10, 123.09, 123.24, 126.70, 127.49, 129.50, 130.13, 130.62,
131.72, 132.47, 132.69, 133.46, 147.79, 149.28, 152.66, 159.32,
161.84; ms: m/z 573 (M+, 10), 574 (M++1, 56), 575 (M++2, 15),
493 (2), 385 (100), 241 (4), 188.9 (26). Anal. Calcd. for
C23H16BrClFN7OS: C, 48.22; H, 2.82; N, 17.12; S, 5.60. Found:
C, 48.16; H, 2.52; N, 16.95; S, 5.74.
1-{[5-(5-Methyl-2-nitrobenzylthio)-4-phenyl-4H-1,2,4-
triazol-3-yl]methyl}-4-(4-chlorophenyl)-1,4-dihydro-5H-
tetrazol-5-one (6w). Yellow needles, yield 99%; mp 167-169º;
1H nmr (deuteriochloroform): ꢀ 2.42 (s, 3H, CH3), 4.79 (s, 2H,
SCH2), 5.21 (s, 2H, CH2), 7.11-8.02 (m, 12H, ArH); 13C nmr
(100 MHz, deuteriochloroform): ꢀ 21.37, 34.23, 39.30, 120.14,
125.54, 126.64, 129.46, 130.15, 130.61, 131.58, 132.65, 131.31,
133.41, 133.54, 145.14, 145.43, 147.76, 149.21, 153.42; ms: m/z
535 (M+, 17), 489 (100), 385 (15), 335 (68), 231 (14), 150 (3),
125 (10). Anal. Calcd. for C24H19ClN8O3S: C, 53.88; H, 3.58; N,
20.93; S, 5.99. Found: C, 53.93; H, 3.42; N, 20.79; S, 6.02.
Methyl(2E)-(2-((5-((4-(4-chlorophenyl)-5-oxo-4,5-dihydro-
5H-tetrazol-1-yl)methyl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)-
methyl)phenyl)-2-(methoxyimino) acetate (6x). Yellow
needles, yield 85%; mp 180-182º; 1H nmr (deuterio-
chloroform): ꢀ 3.79 (s, 3H, CO2CH3), 3.97 (s, 3H, OCH3),
4.32 (s, 2H, SCH2), 5.21 (s, 2H, CH2), 7.10-7.77 (m, 13H,
ArH); 13C nmr (100 MHz, deuteriochloroform): ꢀ 34.92,
39.24, 52.86, 63.64, 120.12, 126.75, 127.58, 128.32, 129.40,
129.56, 129.89, 130.19, 130.29, 131.79, 132.63, 133.31,
Acknowledgement. We should thank Dr Jie Chen for the
tests of biological assay. We also should thank the financial
support from the National Key Project for Basic Research
(2003CB114400, 2002CCA00500), National NSFC (No.
20572030, 20432010, and 20528201), Program for New Century

Jul-Aug 2007 Design and Synthesis of Diheterocyclic Compounds Containing Tetrazolinone and 1,2,4-triazole
943
[7a] Ashton, W. T.; Maccoss, M.; Chang, L. -L.; Chakravarty, P.
K.; Cantone, C. L.; Greenlee, W. J.; Patchett, A. A.; Walsh, T. F.;
European Patent 409,332, 1991; Chem. Abstr. 1991, 115, 29337u; [b]
Starck, D.; Blank, S.; Treiber, H.; Unger, L.; Neumann-Schultz, B.; Le
Bris, T.; Teschendorf, H.; Wicke, K. WO Patent 9,902,503, 1999; Chem.
Abstr. 1999, 130, 110270.
Excellent Talents in University of China and Program for
Excellent Research Group of Hubei Province (No.
2004ABC002).
REFERENCES AND NOTES
[8a] Jalilian, A. R.; Sattari, S.; Bineshmarvasti, M.; Shafiee, A.;
Daneshtalab, M. Arch. Pharm. 2000, 333, 347; [b] Miyauchi, H.;
Kozuki, K.; Tanio, T.; Ohashi, N. Bioorg. Med. Chem. 1996, 4, 263; [c]
Turan-Zitouni, G.; Kaplancikli, Z. A.; Yildiz, M. T.; Chevallet, P.; Kaya,
D. Eur. J. Med. Chem. 2005, 40, 607.
[9a] Horwitz, J. P.; Fisher, B. E.; Tomasewski, A. J. J. Am. Chem.
Soc. 1959, 81, 3076; [b] Yanagi, A. ; Watanabe, Y.; Narabu, S.
European Patent 0,638,561, 1994; Chem. Abstr. 1995, 122, 214081p.
[10] El-Khawass, S. M.; Habib, N. S. J. Heterocycl. Chem. 1989,
26, 177.
[11] Fulop, F.; Semega, E.; Dombi, G.; Bernath, G. J. Heterocycl.
Chem. 1990, 27, 951.
[12] Abbott, W. S. J. Econ. Entomol. 1925, 18, 265.
[13] Sheldrick, G. M. SHELXS-97: Program for crystal structure
refinement; Göttingen, Germany, 1997.
[1] Theodoridis, G.; Hotzman, F. W.; Scherer, L. W.; Smith, B.
A.; Tymonko, J. M.; Wyle, M. J. Pestic. Sci. 1990, 30, 259.
[2] Zou, X.-J.; Jin, G. –Y. J. Heterocycl. Chem. 2001, 38, 993.
[3] Chu, C. -H.; Hui, X. -P.; Xu, P. -F.; Zhang, Z. –Y.; Li, Z. -
C.; Liao, R.-A. Indian J. Chem. Sect. B: Org. Chem. Incl. Med. Chem.
2002, 41, 2436.
[4] Dzygiel, A.; Masiukiewicz, E.; Rzeszotarska, B. J. Agric.
Food Chem. 2002, 50, 1383.
[5] Ma, Y.–M.; Liu, R.-H.; Gong, X.-Y.; Li, Z.; Huang, Q.-C.;
Wang, H.-S.; Song, G.-H. J. Agric. Food Chem. 2006, 54, 7724.
[6] Jagerovic, N.; Hernandez-Folgado, L.; Alkorta, I.; Goya, P.
R.; Navarro, M.; Serrano, A.; Rodriguez de Fonseca, F.; Dannert, M. T.;
Alsasua, A.; Suardiaz, M.; Pascual D.; Martin, M. I. J. Med. Chem.
2004, 47, 2939.