Synthesis and antifungal activity of novel 1,2,4-triazole derivatives containing 1,2,3-thiadiazole moiety

Article abstract of DOI:10.1002/jhet.1656

Starting from carbonic acid diethyl ester, a series of 1,2,4-triazole derivatives containing 1,2,3-thiadiazole were synthesized. Reactions were performed by microwave irradiation or ultrasonic irradiation as well as by conventional heating. The structure of title compounds was characterized by ¹H-NMR, MS, and elemental analyses. The fungicidal activities of these compounds were tested in vivo. Most of title compounds exhibited good antifungal activity against Pseudoperonospora cubensis. Some of title compounds displayed moderate antifungal activities against Fusarium oxysporum, Pseudoperonospora cubensis, Sphaerotheca fuligenea, Corynespora cassiicola, and Xanthomonas axonopodis.

Full text of DOI:10.1002/jhet.1656

690
Synthesis and Antifungal Activity of Novel 1,2,4-Triazole Derivatives
Containing 1,2,3-Thiadiazole Moiety
Vol 51
a
a
b
c
Cheng-Xia Tan,a† Yan-Xia Shi,c† Jian-Quan Weng, Xing-Hai Liu, Wei-Guang Zhao, and Bao-Ju Li
*
*
*
aCollege of Chemical Engineering & Materials Sciences, Zhejiang University of Technology, Hangzhou, 310014, China
bState-Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, China
cInstitute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, 100014, China
*
E-mail: xhliu@zjut.edu.cn or zwg@nankai.edu.cn or libj@mail.caas.net.cn
†Cheng-Xia Tan and Yan-Xia Shi contributed equally to this work.
Received December 7, 2011
DOI 10.1002/jhet.1656
Published online 2 December 2013 in Wiley Online Library (wileyonlinelibrary.com).
Starting from carbonic acid diethyl ester, a series of 1,2,4-triazole derivatives containing 1,2,3-thiadiazole were syn-
thesized. Reactions were performed by microwave irradiation or ultrasonic irradiation as well as by conventional heating.
The structure of title compounds was characterized by 1H-NMR, MS, and elemental analyses. The fungicidal activities
of these compounds were tested in vivo. Most of title compounds exhibited good antifungal activity against Pseudoper-
onospora cubensis. Some of title compounds displayed moderate antifungal activities against Fusarium oxysporum,
Pseudoperonospora cubensis, Sphaerotheca fuligenea, Corynespora cassiicola, and Xanthomonas axonopodis.
J. Heterocyclic Chem., 51, 690 (2014).
INTRODUCTION
scaffold. Some 1,2,4-triazole derivatives were synthesized and
characterized by 1H-NMR, MS, and elemental analysis. The
biological activities of these compounds were tested in vivo.
Heterocyclic compounds have been received considerable
attentions in recent years because of their pharmacological
and pesticidal importance [1–3]. 1,2,3-Thiadiazole moiety
has been claimed to have beneficial, medicinal, and agricul-
tural applications, because of their exhibited excellent biolog-
ical activities such as fungicidal [4], anti-HBV [5], herbicidal
[6], anti-TMV [7], antihistaminic [8], antifungal [9], and
antibacterial [10]. Also, they are useful intermediates in or-
ganic synthesis, and the 1,2,3-thiadiazole chemistry has been
widely studied. For example, after the plant inducers such as
thiadinal [11] and BTH [12] were discovered (Figure 1),
1,2,3-thiadiazoles pesticide has become one of the focuses
of developing agrochemicals in academia and industries.
Furthermore, it is reported that 1,2,4-triazoles possess a
diverse range of bioactivities in medicinal and agrochemical
field, such as anticancer [13], anti-inflammatory [14], antimi-
crobial [15], herbicidal [16], and insecticidal [17] activity.
Some compounds had been developed as commercial fungi-
cides (Figure 2), such as triadimefon, triadimenol, flusilazole,
and so on. Because of their diverse properties, 1,2,4-triazole
fungicides may become one of the focuses in drug research.
In view of these facts mentioned earlier and also as a part of
our work [18] on the synthesis of bioactive lead compounds,
the title compounds were designed by introducing cyclopro-
pane and 1,2,3-thiadiazole pharmacophore into 1,2,4-triazole
RESULTS AND DISCUSSION
Synthesis and spectra. The synthesis procedures for title
compound were shown in Scheme 1. The intermediate 6
is reacted with substituted benzyl chloride to afford
intermediate 7 at RT for 24h. To optimize the reaction
condition and reaction times, microwave and ultrasonic
irradiation were employed. NaOH/DMF/H2O system was
applied under microwave irradiation at 90ꢀC for 10min.
Also, K2CO3/DMF condition was tried under ultrasound
irradiation at RT for 50min. The results are shown in
Table 1. The proton magnetic resonance spectra of the
triazoles have been recorded in CDCl3. The triazole
intermediates can exist either as a thione or the thiol
tautomeric forms or as an equilibrium mixture of both
forms, because they have a thioamide, —NH—C(═S)
function. The chemical shift at d 10.86 as a singlet may be
due to SH proton, indicating that 6 existed not as thione but
as the thiol tautomeric forms in solution [19]. The signal of
CH2 protons of thioether and sulfone neighboring to the
triazole ring was observed at d 4.73–4.53 ppm, respectively,
except compound 7j and 7k. The chemical shifts around
© 2013 HeteroCorporation

May 2014
1,2,4-Triazole with Antifungal Activities
691
N
control. Lots of the title compounds showed good control
efficacy of some of the test fungi at a concentration of
500 mg/mL. Meanwhile, all of these tested compounds
were found safe for the cucumber plants. As shown in
Table 1, compound 7c, 7d, 7f, 7j, and 7k exhibited a
significant inhibition effect against P. cubensis, and the
fungicidal activities (control efficacy of 71–83%) were
higher than those of thiophanate methyl, jinggangmeisu,
and zhongshengmycin. All these compounds did not
display obvious fungicidal activities against R. solanii.
All of them were less effective than that of the control
jinggangmeisu. Compound 7f, 7i, 7j, and 7k showed fair
fungicidal activity (control effect 69.9–86.2%) against F.
oxysporum. All of the four compounds were similar with
that of thiophanate methyl. Compound 7d, 7j, and 7k,
held about 50% control effect against S. fuligenea. For
the X. axonopodis and P. syringae pv. lachrymans, it was
found that most of the compounds had moderate
N
N
N
H
N
Cl
S
S
O
MeS
O
thiadinal
BTH
Figure 1. The commercial pesticides contain 1,2,3-thiadiazole group.
3.0 ppm are the methyl of 1,2,3-thiadiazole. All the title
compounds of mass spectra are M + H peak.
Antifungal activity and SAR. The in vivo fungicidal
results of title compounds against Fusarium oxysporum,
Pseudoperonospora cubensis, Sphaerotheca fuligenea,
Corynespora cassiicola, Xanthomonas axonopodis,
Pseudomonas syringae pv. lachrymans, and Rhizoctonia
solanii were listed in Table 2; thiophanate methyl,
jinggangmeisu, and zhongshengmycin were used as a
F
O
O
OH
O
N
N
N
Si
F
N
N
N
Cl
N
Cl
N
N
Triadimefon
Triadimenol
Flusilazole
Figure 2. The commercial pesticides contain 1,2,4-triazole group.
Scheme 1. The synthetic route of title compounds.
O
O
O
O
N
O
O
80% NH2NH2 H2O
r.t.
O
HN
NH2
O
O
N
H
O
O
EtOH, r.t.
O
1
2
N
N
80% NH2NH2 H2O
Ref.
SOCl2, CH2Cl2
r.t.
H
N
N
N
O
S
S
NH2
O
4
O
3
N
N
N
S
H
N
NCS
1. NaOH, Ref.
2. HCl
N
N
SH
N
S
N
N
H
N
S
EtOH, Ref.
H
O
5
6
N
N
R1
N
S
K2CO3, RX
DMF, r.t.
N
N
S
7a-k
R= 2-ClPh, 3-ClPh, 4-ClPh, 2,4-Cl2Ph, 3,4-Cl2Ph, 4-BuPh, 4-OMePh, Ph, 3-CNPh, propinyl, heptyl
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

692
C.-X. Tan, Y.-X. Shi, J.-Q. Weng, X.-H. Liu, W.-G. Zhao, and B.-J. Li
Vol 51
Table 1
spectra were measured on a AV 400 instrument (Bruker,
Fallanden, Switzerland) using TMS as an internal
standard and CDCl3 as the solvent. Mass spectra were
recorded on a Thermo Finnigan LCQ Advantage LC/mass
detector instrument (San Jose, CA). Elemental analyses
were performed on a Vario EL elemental analyzer (Hanau,
Germany). Microwave activation was carried out with CEM
Discover focused microwave (2450 MHz, 300 W; Matthews,
NC). Ultrasonic activation was carried out with KQ-
200KDB ultrasonic apparatus (Kunshan, Jiangsu, China).
All the reagents are of analytical grade or freshly prepared
before use.
The reaction condition of target compounds.
Compound
Condition
K2CO3/DMF
K2CO3/DMF
K2CO3/DMF/H2O
Time
Yield
7h
7h
7h
RT
24 h
50 min
10 min
83%
84%
88%
US/RT
MW/90ꢀC
US, ultrasonic; MW, microwave.
fungicidal activity, except that compound 7g (78.02%)
displayed moderate control effect against X. axonopodis,
which was similar to that of the most active fungicide
zhongshengmycin (87.86%). Compound 7c showed
moderate control effect (66.06%) against C. cassiicola,
and it was had same level with zhongshengmycin
(75.19%). In general, the in vivo fungicidal activity of
compounds 7 indicated that the change of substituent
affects the activity with the trend alkyl > aromatic. For
example, 7j and 7k exhibited higher fungicidal activity
than that of substituted benzene rings. In addition, the
substituted benzene ring compound with p-Cl or 2,4-Cl2
lead to higher fungicidal activity against P. cubensis.
General procedure. The title compounds were synthesized
according to the route shown in Scheme 1, and the yields were not
optimized.
Synthesis of intermediates.
Preparation of 4-methyl-1,2,3-thiadiazole-5-carbohydrazide.
Intermediate 4-methyl-1,2,3-thiadiazole-5-carboxylic acid hydrazide
4 was synthesized according to the literature [5]. A mixture of
carbonic acid diethyl ester (11.8 g, 0.1 mol) and hydrazine hydrate
(5.6 mL, 0.095 mol, 85%) was added into a 250 mL round-bottom
flask equipped with a condenser. The reaction mixture was heated
to 50ꢀC, stirred for 20 min, and then stirred at RT for 30 h. Water,
ethanol, and excess carbonic acid diethyl ester were distilled off
under reduced pressure. After dryness, a white crystal ethyl
hydrazinecarboxylate 1 (9.88 g) was obtained with a yield of 95%.
A solution containing the compound 1 (6.36 g, 0.06 mol) in ethanol
(16.7 mL) was added dropwise to a solution of ethyl acetoacetate
(7.8 g, 0.06 mol) in ethanol (3.7 mL) slowly. After stirring for 6 h at
RT, water and ethanol were distilled off under reduced pressure,
CONCLUSIONS
In summary, we have synthesized some novel 1,2,4-triazole
derivatives containing cyclopropane ring and 1,2,3-thiadiazole
ring under conventional, microwave, and ultrasonic condition
with good yields. The preliminary bioassays showed that
some of the compounds had good antifungal activities.
and
a white product ethyl 2-(4-ethoxy-4-oxobutan-2-ylidene)
hydrazinecarboxylate 2 (12.8 g) was obtained with a yield of 99%.
To a solution of 3-ethoxycarbonylhydrazonoacetic acid ethyl ester
(12.8 g, 0.059 mol) in dichloromethane (25 mL), thionyl chloride
(20 mL) was added dropwise in batches below 20ꢀC. After stirring
in an ice water bath for 1 h, the reaction mixture was permitted to
stand for 20 h at RT. The excess thionyl chloride and
dichloromethane were distilled off, and the remaining residue was
subject to fractional distillation under reduced pressure. A slight
EXPERIMENTAL
Instruments. Melting points were determined using an
X-4 apparatus (Beijing, China) and uncorrected. 1H-NMR
yellowish oil ethyl 4-methyl-1,2,3-thiadiazole-5-carboxylate
3
Table 2
Antifungal activity of title compounds (percent relative control efficacy) at 500 mg/mL.
No.
PC
PS
CC
FO
SF
XA
RS
7a
7b
7c
7d
7e
7f
7g
7h
45.92
68.54
79.24
83.04
64.46
78.89
45.04
54.02
69.17
71.07
81.62
38.32
35.92
8.04
36.50
20.39
48.87
57.47
54.45
54.48
43.29
43.55
24.41
6.47
25.18
27.59
66.06
55.99
14.09
53.72
39.60
48.01
28.99
21.38
54.03
27.72
45.47
65.13
53.61
53.61
59.87
58.62
53.61
72.41
53.61
66.14
86.21
69.91
71.16
78.68
59.87
28.53
27.07
17.73
32.48
47.23
10.51
29.57
29.83
50.11
44.53
58.58
42.63
30.15
19.81
65.08
52.07
34.04
44.38
59.57
26.13
49.95
78.02
14.25
8.39
43.03
45.96
47.92
ꢁ3.15
87.86
12.07
6.66
8.36
4.97
16.12
10.84
3.59
8.36
3.21
4.51
9.60
10.84
93.84
10.18
7i
7j
7k
30.17
49.85
49.20
75.19
Thiophanate methyl
Jinggangmeisu
Zhongshengmycin
PC, Pseudoperonospora cubensis; PS, Pseudomonas syringae pv. lachrymans; CC, Corynespora cassiicola; FO, Fusarium oxysporum; SF, Sphaerotheca
fuligenea; XA, Xanthomonas axonopodis; RS, Rhizoctonia solanii.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2014
1,2,4-Triazole with Antifungal Activities
693
cyclopropane-CH), 4.60 (s, 2H, CH2), 7.32 (d, J= 7.96 Hz, 2H,
Ph—H), 7.45 (d, J=7.96Hz, 2H, Ph—H); ESI–MS: 365 [M + 1]+;
Elemental analysis for C15H14ClN5S2: found C 49.87, H 3.99, N
19.34; Calcd C 49.51, H 3.88, N 19.25.
(7.95 g) was obtained with a yield of 77%. A mixture of 4-methyl-
1,2,3-thiadiazole-5-carboxylic acid ethyl ester 3 (1.72g, 10mmol)
and hydrazine hydrate (12 mmol) in 10 mL of methanol was stirred
vigorously for 0.5 h at RT, the mixture was filtered, and the solid
was washed with cold methanol. After drying, the solid was
recrystallized from methanol to give intermediate 4-methyl-1,2,3-
thiadiazole-5-carboxylic acid hydrazide 4.
5-(4-Cyclopropyl-5-((2,4-dichlorobenzyl)thio)-4H-1,2,4-triazol-
3-yl)-4-methyl-1,2,3-thiadiazole (7d).
This compound was
obtained as white solid, yield 89.3%, mp 114–115ꢀC;
1H-NMR (400 M, CDCl3) d: 0.81–0.91 (m, 2H, cycloprane-CH2),
1.21–1.26 (m, 2H, cycloprane-CH2), 3.03 (s, 3H, CH3), 3.06–3.12
(m, 1H, cyclopropane-CH), 4.73 (s, 2H, CH2), 7.22 (d, J=8.27Hz,
1H, Ph—H), 7.45 (s, 1H, Ph—H), 7.70 (d, J=8.22Hz, 1H, Ph—H);
ESI–MS: 399 [M + 1]+; Elemental analysis for C15H13Cl2N5S2:
found C 45.33, H 3.43, N 17.66; Calcd C 45.23, H 3.29, N 17.58.
5-(4-Cyclopropyl-5-((3,4-dichlorobenzyl)thio)-4H-1,2,4-triazol-
Preparation of isothiocyanatocyclopropane.
The isothi-
ocyanatocyclopropane was synthesized according to the reference [19].
N-Cyclopropyl-2-(4-methyl-1,2,3-thiadiazole-5-carbonyl)
hydrazinecarbothioamide (5).
5-carboxylic acid hydrazide
4-Methyl-1,2,3-thiadiazole-
4 mixed with 1.5g of
isothiocyanatocyclopropane for refluxing about 3 h in ethanol.
After cooling, lots of solid were obtained. The solid was filtered,
dried, and recrystallized from methanol to give intermediate
N-cyclopropyl-2-(4-methyl-1,2,3-thiadiazole-5-carbonyl)hydrazine-
carbothioamide 5: yellow crystal, yield 87.6%, mp 120–121ꢀC, 1H-
NMR (400 M, CDCl3): 0.40–0.79 (m, 4H, cyclopropane-CH2), 2.78
(m, 1H, cyclopropane-CH), 3.31 (s, 3H, Me).
3-yl)-4-methyl-1,2,3-thiadiazole (7e).
This compound was
obtained as white solid, yield 88.5%, mp 95–96ꢀC;
1H-NMR (400 M, CDCl3) d: 1.06–1.13 (m, 2H, cycloprane-CH2),
1.21–1.27 (m, 2H, cycloprane-CH2), 3.03 (s, 3H, CH3), 3.05–3.10
(m, 1H, cyclopropane-CH), 4.58 (s, 2H, CH2), 7.38 (d, J=8.35Hz,
1H, Ph—H), 7.42(d, J=8.12Hz, 1H, Ph—H), 7.61 (s, 1H, Ph—
H); ESI–MS: 399 [M + 1]+; Elemental analysis for C15H13Cl2N5S2:
found C 45.41, H 2.97, N 17.88; Calcd C 45.23, H 3.29, N 17.58.
5-(5-((4-(tert-Butyl)benzyl)thio)-4-cyclopropyl-4H-1,2,4-triazol-
4-Cyclopropyl-5-(4-methyl-1,2,3-thiadiazol-5-yl)-4H-1,2,4-triazole-
3-thiol (6). N-cyclopropyl-2-(4-methyl-1,2,3-thiadiazole-5-carbonyl)
hydrazinecarbothioamide 5 (10 mmol) mixed with 15 mL, 2N
NaOH for refluxing about 4 h. After cooling, 4N HCl was
added, and lots of solid were obtained. The solid was filtered,
dried, and recrystallized from methanol to give intermediate
4-cyclopropyl-5-(4-methyl-1,2,3-thiadiazol-5-yl)-4H-1,2,4-triazole
3-yl)-4-methyl-1,2,3-thiadiazole (7f).
This compound was
obtained as white solid, yield 39.8%, mp 113–114ꢀC; 1H-NMR
(400 M, CDCl3) d: 0.86–1.02 (m, 2H, cycloprane-CH2), 1.08–1.13
(m, 2H, cycloprane-CH2), 1.24 (s, 9H, CH3), 2.92 (s, 3H, CH3),
2.96–3.05 (m, 1H, cyclopropane-CH), 4.58 (s, 2H, CH2), 7.19 (s,
2H, Ph—H), 7.24–7.28 (m, 1H, Ph—H), 7.31–7.39 (s, 1H, Ph—H);
ESI–MS: 386 [M + 1]+; Elemental analysis for C19H23N5S2: found
C 59.05, H 6.25, N 18.43; Calcd C 59.19, H 6.01, N 18.16.
1
-3-thiol 6: yellow crystal, yield 85.6%, mp 205–209ꢀC, H-NMR
(400M, CDCl3): 1.13–1.25 (m, 4H, cyclopropane-CH2), 2.42
(s, 3H, Het—Me), 2.91–2.97 (m, 1H, cyclopropane-CH), 10.86
(br, 1H, SH).
General procedure for thioether. To a stirred solution of 4-
cyclopropyl-5-(4-methyl-1,2,3-thiadiazol-5-yl)-4H-1,2,4-triazole-
3-thiol 6 (1.5 g, 5.1 mmol) and K2CO3 (0.2 g, 5.6 mmol) in DMF
(15 mL), a mixture of a substituted benzyl chloride (5.6 mmol)
was added dropwise. The resulting mixture was stirred at RT for
overnight. The mixture was poured into water. The precipitate
formed was filtered off and recrystallized from petroleum ether/
acetone to give 7 in good yields.
5-(4-Cyclopropyl-5-((4-methoxybenzyl)thio)-4H-1,2,4-triazol-
3-yl)-4-methyl-1,2,3-thiadiazole (7g).
This compound was
obtained as white solid, yield 87.3%, mp 119–120ꢀC; 1H-NMR
(400M, CDCl3) d: 0.89–0.94 (m, 2H, cycloprane-CH2), 1.12–
1.25 (m, 2H, cycloprane-CH2), 3.02 (s, 3H, CH3), 3.09–3.15 (m,
1H, cyclopropane-CH), 3.82 (s, 3H, OCH3), 4.64 (s, 2H, CH2),
6.88 (d, J = 7.86 Hz, 2H, Ph—H), 7.41 (d, J = 7.86Hz, 2H, Ph—
H); ESI–MS: 360 [M + 1]+; Elemental analysis for C16H17N5OS2:
found C 53.33, H 4.88, N 19.79; Calcd C 53.46, H 4.77, N 19.48.
5-(5-(Benzylthio)-4-cyclopropyl-4H-1,2,4-triazol-3-yl)-4-methyl-
5-(5-((2-Chlorobenzyl)thio)-4-cyclopropyl-4H-1,2,4-triazol-3-yl)-
4-methyl-1,2,3-thiadiazole (7a). This compound was obtained as
1
white solid, yield 78.5%, mp 133–134ꢀC; H-NMR (400 M, CDCl3)
d: 0.70–0.84 (m, 2H, cycloprane-CH2), 1.09–1.15 (m, 2H, cycloprane-
CH2), 2.86–2.93 (m, 1H, cyclopropane-CH), 2.94 (s, 3H, CH3), 4.66
(s, 2H, CH2), 7.14 (s, 1H, Ph—H), 7.20–7.24 (m, 1H, Ph—H), 7.34
(d, J=7.62Hz, 1H, Ph—H), 7.58 (d, J=7.24Hz, 1H, Ph—H); ESI–
MS: 365 [M + 1]+; Elemental analysis for C15H14ClN5S2: found C
49.56, H 3.65, N 19.44; Calcd C 49.51, H 3.88, N 19.25.
5-(5-((3-Chlorobenzyl)thio)-4-cyclopropyl-4H-1,2,4-triazol-3-yl)-
4-methyl-1,2,3-thiadiazole (7b). This compound was obtained as
white solid, yield 86.7%, mp 131–132ꢀC; 1H-NMR (400 M,
CDCl3) d: 0.82–0.96 (m, 2H, cycloprane-CH2), 1.21–1.26 (m, 2H,
cycloprane-CH2), 2.99 (s, 3H, CH3), 3.03–3.18 (m, 1H,
cyclopropane-CH), 4.62 (s, 2H, CH2), 7.30–7.35 (m, 2H, Ph—H),
7.36–7.44 (m, 1H, Ph—H), 7.49 (s, 1H, Ph—H); ESI–MS: 365
[M + 1]+; Elemental analysis for C15H14ClN5S2: found C 49.56, H
3.78, N 19.13; Calcd C 49.51, H 3.88, N 19.25.
1,2,3-thiadiazole (7h).
This compound was obtained as white
1
solid, yield 77.9%, mp 122–123ꢀC; H-NMR (400 M, CDCl3) d:
0.71–0.84 (m, 2H, cycloprane-CH2), 1.08–1.14 (m, 2H, cycloprane-
CH2), 2.89–2.93 (m, 1H, cyclopropane-CH), 2.94 (s, 3H, CH3), 4.53
(s, 2H, CH2), 7.21–7.29 (m, 3H, Ph—H), 7.39 (m, 2H, Ph—H);
ESI–MS: 330 [M + 1]+; Elemental analysis for C15H15N5S2: found C
54.44, H 4.76, N 21.01; Calcd C, 54.69; H, 4.59; N, 21.26.
3-(((4-Cyclopropyl-5-(4-methyl-1,2,3-thiadiazol-5-yl)-4H-1,2,4-
triazol-3-yl)thio)methyl)benzonitrile (7i).
This compound was
obtained as white solid, yield 82.1%, mp 133–134ꢀC; 1H-NMR
(400 M, CDCl3) d: 0.79–0.83 (m, 2H, cycloprane-CH2), 1.13–1.18 (m,
2H, cycloprane-CH2), 2.95 (s, 3H, CH3), 2.97–3.02 (m, 1H,
cyclopropane-CH), 4.53 (s, 2H, CH2), 7.37 (t, J=7.22Hz, 1H, Ph—H),
7.51 (d, J=7.22Hz, 1H, Ph—H), 7.71(t, J=7.84Hz, 2H, Ph—H);
ESI–MS: 355 [M + 1]+; Elemental analysis for C16H14N6S2: found C
54.21, H 3.70, N 23.99; Calcd C, 54.22; H, 3.98; N, 23.71.
5-(5-((4-Chlorobenzyl)thio)-4-cyclopropyl-4H-1,2,4-triazol-3-yl)-
4-methyl-1,2,3-thiadiazole (7c). This compound was obtained as
white solid, yield 37.0%, mp 112–113ꢀC; 1H-NMR (400 M,
CDCl3) d: 0.85–0.94 (m, 2H, cycloprane-CH2), 1.20–1.25 (m, 2H,
cycloprane-CH2), 3.03 (s, 3H, CH3), 3.04–3.12 (m, 1H,
5-(4-Cyclopropyl-5-(prop-2-yn-1-ylthio)-4H-1,2,4-triazol-3-yl)-
4-methyl-1,2,3-thiadiazole (7j). This compound was obtained as
white solid, yield 76.8%, mp 107–108ꢀC; 1H-NMR (400 M, CDCl3)
d: 0.78–0.94 (m, 2H, cycloprane-CH2), 1.17–1.21 (m, 2H,
Journal of Heterocyclic Chemistry
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694
C.-X. Tan, Y.-X. Shi, J.-Q. Weng, X.-H. Liu, W.-G. Zhao, and B.-J. Li
Vol 51
cycloprane-CH2), 2.24 (s, 1H, CH), 2.95 (s, 3H, CH3), 2.99–3.11 (m,
1H, cyclopropane-CH), 4.09 (s, 2H, CH2); ESI–MS: 278 [M + 1]+;
Elemental analysis for C11H11N5S2: found C 47.88, H 4.23, N 25.14;
Calcd C, 47.63; H, 4.00; N, 25.25.
5-(4-Cyclopropyl-5-(octylthio)-4H-1,2,4-triazol-3-yl)-4-methyl-
1,2,3-thiadiazole (7k). This compound was obtained as white solid,
yield 80.5%, mp 67–68ꢀC; 1H-NMR (400 M, CDCl3) d: 0.79–0.86 (m,
5H, cycloprane-CH2 and CH2), 1.14–1.24 (m, 11H, cycloprane-CH2
and CH2), 1.36–1.44 (m, 2H, CH2), 1.74–1.81 (m, 2H, CH2), 2.95 (s,
3H, CH3), 2.99–3.05 (m, 1H, cyclopropane-CH), 3.33 (t, 3H, CH3);
ESI–MS: 352 [M + 1]+; Elemental analysis for C16H25N5S2: found C
54.86, H 7.24, N 20.20; Calcd C, 54.67; H, 7.17; N, 19.92.
Acknowledgments. This work was supported by National Natural
Science Foundation of China (No. 21002090, 21172124), The Key
Innovation Team of Science and Technology in Zhejiang Province
(2010R50018-06), and the National Key Technologies R&D
Program (2011BAE06B03-01).
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relative control efficacy ð%Þ ¼ ðCK ꢁ PTÞ=CK ꢂ 100%
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet