Synthesis and fungicidal activity of (1Z, 3Z)-4,4-dimethyl-1- substitutedphenyl-2-(1H-1,2,4-triazol-1-yl)-pent-1-en-3-one O-[2,4- dimethylthiazole(or 4-methyl-1,2,3-thiadiazole)]-5-carbonyl oximes

Article abstract of DOI:10.1002/jhet.783

A series of novel (Z)-1-tert-butyl (or phenyl)-2-(1H-1,2,4-triazol-1-yl)- ethanone O-[2,4-dimethylthiazole (or 4-methyl-1,2,3-thiadiazole) -5-carbonyl] oximes 5a-5c and (1Z, 3Z)-4,4-dimethyl-1-substitutedphenyl-2-(1H-1,2,4-triazol- 1-yl)-pent-1-en-3-one O-[2,4-dimethylthiazole (or 4-methyl-1,2,3-thiadiazole)-5- carbonyl] oximes 6a-6e were synthesized by the condensations of (Z)-1-tert-butyl (or phenyl)-2-(1H-1,2,4-triazol-1-yl)-ethanone oximes 3 or (1Z, 3Z)-4,4-dimethyl-1-substitutedphenyl-2-(1H-1,2,4-triazol-1-yl)-pent-1-en-3-one oximes 4 with 2,4-dimethylthiazole-5-carbonyl chloride or 4-methyl-1,2,3- thiadiazole-5-carbonyl chloride in the basic condition. Their structures were confirmed by IR, ¹H NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays showed the title compounds 5 and 6 exhibited moderate to good fungicidal activities. For example, compound 6c possessed 86.4% inhibition against Fusarium oxysporum, and compound 6b exhibited 86.4 and 100% inhibition against Fusarium oxysporum and Cercospora arachidicola Hori at the concentration of 50 mg/L, respectively.

Full text of DOI:10.1002/jhet.783

May 2012
Synthesis and Fungicidal Activity of (1Z, 3Z)-4,4-Dimethyl-1-substituted-
phenyl-2-(1H-1,2,4-triazol-1-yl)-pent-1-en-3-one O-[2,4-dimethylthiazole
(or 4-methyl-1,2,3-thiadiazole)]-5-carbonyl Oximes
a
511
Hui-Yu Mao,a,b Hong Song,a,b and De-Qing Shi
*
aKey Laboratory of Pesticide and Chemical Biology of Ministry of Education,
College of Chemistry, Central China Normal University, Wuhan 430079, People’s Republic of China
bWuhan Bioengineering Institute, Yangluo District, Wuhan 430415, People’s Republic of China
*
E-mail: chshidq@mail.ccnu.edu.cn
Received September 7, 2010
DOI 10.1002/jhet.783
View this article online at wileyonlinelibrary.com.
A series of novel (Z)-1-tert-butyl (or phenyl)-2-(1H-1,2,4-triazol-1-yl)-ethanone O-[2,4-dimethylthiazole
(or 4-methyl-1,2,3-thiadiazole) ꢀ5-carbonyl] oximes 5a–5c and (1Z, 3Z)-4,4-dimethyl-1-substitutedphenyl-
2-(1H-1,2,4-triazol-1-yl)-pent-1-en-3-one O-[2,4-dimethylthiazole (or 4-methyl-1,2,3-thiadiazole)-5-carbonyl]
oximes 6a–6e were synthesized by the condensations of (Z)-1-tert-butyl (or phenyl)-2-(1H-1,2,4-triazol-1-yl)-
ethanone oximes 3 or (1Z, 3Z)-4,4-dimethyl-1-substitutedphenyl-2-(1H-1,2,4-triazol-1-yl)-pent-1-en-3-one
oximes 4 with 2,4-dimethylthiazole-5-carbonyl chloride or 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride
in the basic condition. Their structures were confirmed by IR, 1H NMR, mass spectroscopy, and elemental
analyses. The results of preliminary bioassays showed the title compounds 5 and 6 exhibited moderate to
good fungicidal activities. For example, compound 6c possessed 86.4% inhibition against Fusarium
oxysporum, and compound 6b exhibited 86.4 and 100% inhibition against Fusarium oxysporum and
Cercospora arachidicola Hori at the concentration of 50 mg/L, respectively.
J. Heterocyclic Chem., 49, 511 (2012).
INTRODUCTION
developed as one of neonicotinoid insecticides, and
methidathion was used cholinesterase inhibitor, which
acts as nonsystemic insecticide and acaricide with con-
tact and stomach action, whereas flurazole has been
used as herbicides or their safeners, and ethaboxam
acted as fungicides. acibenzolar-S-methyl and tiadinil
were developed and used as plant activators, which
induces fungicide resistance in rice plants; however,
thidiazuron was used as plant growth regulator (see
Fig. 1). On the other hand, oxime ester derivatives are
very important agrochemicals and are receiving more
and more attention due to their widespread biological
activities[14], some of them can be used as insecticides
[15,16], fungicides [17,18], herbicides (such as trifop-
sime and pyribenzoxim)[19], and plant virucides (for
example, antiviral agent against tobacco mosaic virus
[20]), which are widely used in the worldwide plant pro-
tection. To find novel fungicide lead compounds with
high activity and low toxicity, we designed and synthe-
sized a series of novel target compounds 5 and 6, which
The application of agrochemicals to protect vegetable
and cereal crops is a virtual and convenient approach
for modern agriculture. This has provided healthy crops
and increased yields as well as economic benefits for
decades. The main purpose of the research for agro-
chemicals is to develop novel active compounds with
lower application doses, high selectivity, and benign
environment [1,2]. The triazole fungicides, as an impor-
tant class of agrochemicals, have played a major role in
crop protection [3–5]. The introduction of these sterol
biosynthesis inhibitors represented a significant progress
in the chemical control of fungal diseases. More than 30
triazole fungicides such as uniconazole, diniconazole,
paclobutrazol, and flusilazole, have been commercial-
ized. Recently, heterocyclic compounds containing nitro-
gen, such as thiazole and 1,2,3-thiadiazole derivatives as
two kinds of heterocyclic compounds with a wide spec-
trum of remarkable biological activities, are widely used
in agrochemicals [6–13]. For example, clothianidin was
© 2012 HeteroCorporation

512
H.-Y. Mao, H. Song, and D.-Q. Shi
Vol 49
hydroxylamine hydrochloride in the presence of potassium
carbonate and methanol afforded (Z)-1-tert-butyl (or phenyl)-
2-(1H-1,2,4-triazol-1-yl)-ethanone oximes 3 or (1Z, 3Z)-4,
4-dimethyl-1-substitutedphenyl-2-(1H-1,2,4-triazol-1-yl)-
pent-1-en-3-one oximes 4 in 75–89% yields, which
reacted with 2,4-dimethylthiazole-5-carbonyl chloride or
4-methyl-1,2,3-thiadiazole-5-carbonyl chloride in the
presence of triethylamine in chloroform at 10–15ꢁC to get
the title compounds 5 and 6 in moderate to excellent yields.
The structures of compounds 5 and 6 were deduced
1
Figure 1. Some commercialized pesticides containing thiazole and
thiadiazole moieties.
from their spectral data (IR, H NMR, and ESI-MS) and
elemental analyses, which were listed in the experimen-
tal part. Because of the C¼C or (and) C¼N bonds, it
probably existed in E- and Z-isomers in compounds 3
and 4 and target molecules 5 and 6. In the 1H NMR
spectra of 5 and 6, the t-butyl protons displayed as a
singlet with chemical shift d between 1.0 and 1.3; the
protons of two methyl linking with thiazole and 1,2,3-
thiadiazole also showed two singlet and a singlet with
chemical shifts d 2.7, 2.8, and the methyl protons link-
ing with 1,2,3-thiadiazole displayed as a singlet with
chemical shifts d between 2.9 and 3.1; the alkene proton
also exhibited as a singlet in d 7.6; whereas the 1,2,4-
triazole protons showed two singlets with chemical
shifts d 8.0 and 8.2, respectively. These data indicated
the triazole ring is bound via an oxime ester bridge to a
2,4-dimethylthiazole or 4-methyl-1,2,3-thiadiazole units.
Herein, we report the synthesis and fungicide activities
of the title compounds 5 and 6 in this article (Scheme 1).
RESULTS AND DISCUSSION
1-(t-Butyl)-2-(1H-1,2,4-triazol-1-yl)ethanone (1a) reacted
with aromatic aldehydes in the presence of piperidine to
obtain 3-(substitutedphenyl)-1-t-butyl-2-(1H-1,2,4-triazol-
1-yl)prop-2-en-1-ones (2) as Z- and E-isomer mixtures. After
purified by flash column chromatography, pure Z-isomers 2
were obtained; Treatment of 1(1a, and 1b) and 2 with
Scheme 1. Synthetic route to compounds 5 and 6.
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DOI 10.1002/jhet

May 2012
Synthesis and Fungicidal Activity of (1Z, 3Z)-4,4-Dimethyl-1-substitutedphenyl-2-(1H-1,2,
513
4-triazol-1-yl)-pent-1-en-3-one O-[2,4-dimethylthiazole(or 4-methyl-1,2,3-thiadiazole)]-5-carbonyl Oximes
compounds 5 and 6 are existed as single isomers.
According to the reported literatures [21,22], the t-butyl
protons and alkene proton of the Z-isomer of 2 are
shifted downfield with chemical shifts d 1.2–1.5 and
7.5, respectively; whereas these protons in E-isomer
are presented in 1.0 and 6.8, respectively. So, in this ar-
ticle, the C¼C bonds in both compounds 4 and 6 are
existed as Z-isomer. Moreover, according to the related
literature report [23] and our previous X-ray diffraction
data [24], the C¼N bonds of compounds 5 and 6 are all
existed as Z configurations. IR spectra of compounds 5
and 6 showed normal stretching absorption bands, indicating
the existence Ar-H (ꢂ3050 cmꢀ1), C¼O (ꢂ1750 cmꢀ1),
C¼N (ꢂ1650 cmꢀ1), and Ar (1580, 1510, and 1480 cmꢀ1).
The ESI mass spectra of compounds 5 and 6 revealed the
existence of the molecular ion peaks and strong M+K or
M+Na peaks, which were in good accordance with the
given structures of products.
against the five fungi. Second, compounds 6 containing
2,4-dimethylthiazole moiety seems to display better
activities than that of 4-methyl-1,2,3-thiadiazole moiety.
Further exploring of structure-activity relationship need
more experimental results to support. Further biological
activity (in vivo) investigations are on the way.
In conclusion, a series of novel (Z)-1-tert-butyl (or
phenyl)-2-(1H-1,2,4-triazol-1-yl)-ethanone O-[2,4-
dimethylthiazole (or 4-methyl-1,2,3-thiadiazole)-5-carbonyl]
oximes 5a–5c and (1Z, 3Z)-4,4-dimethyl-1-substituted-
phenyl-2-(1H-1,2,4-triazol-1-yl)-pent-1-en-3-one O-[2,4-
dimethylthiazole (or 4-methyl-1,2,3-thiadiazole)-5-carbonyl]
oximes 6a–6e were designed and synthesized. The results
of preliminary bioassays showed the title compounds 5
and 6 exhibited moderate to good fungicidal activities. For
example, compound 6c possessed 86.4% inhibition against
Fusarium oxysporum, and compound 6b exhibited 86.4
and 100% inhibition against Fusarium oxysporum and
Cercospora arachidicola Hori at the concentration of
50 mg/L, respectively.
Biological activity. Fungicidal activity. The preliminary
fungicidal activity of the target compounds 5 and 6
was evaluated by the classic plate method at the
concentration of 50 mg/L, which was described in the
experimental part. The five fungi used, Fusarium
oxysporium, Physalospora piricola Nose, Alternaria
solani, Cercospora arachidicola Hori, and Gibberella
sanbinetti, belong to the group of field fungi and were
isolated from corresponding crops. The activities data
were also listed in Table 1. The results indicated that
most of compounds 5 and 6 exhibit moderate to good
inhibitory activities against the above five fungi. For
example, compound 6c possessed 86.4% inhibition against
Fusarium oxysporum, and compound 6b exhibited 86.4
and 100% inhibition against Fusarium oxysporum and
Cercospora arachidicola Hori at the concentration of
50 mg/L, respectively. As for preliminary structure-activity
relationship, first, most of compounds 6 exhibited better
fungicidal activity than compounds 5, this result indicated
that C¼C moiety introduced to the target molecular
skeleton was useful for the improvement of fungicidal
activity, and compound 6b showed the best activities
EXPERIMENTAL
Melting points were determined with a WRS-1B digital
1
melting point apparatus and are uncorrected. H NMR spectra
was recorded with a Varian Mercury PLUS 400 (400 MHz)
and Varian Mercury PLUS 600 (600 MHz) spectrometer with
TMS as the internal reference and CDCl3 as the solvent,
whereas mass spectra were obtained with an Applied Biosys-
tems API 2000 LC/MS/MS (ESI-MS) spectrometer. IR spectra
were measured by
a Nicolet NEXUS470 spectrometer.
Elemental analyses were performed with an Elementar Vario
ELШ CHNSO elemental analyzer. (1Z, 3Z)-4,4-dimethyl-1-
substitutedphenyl-2-(1H-1,2,4-triazol-1-yl)-pent-1-en-3-one
was prepared by the Knoevenagel reactions of 1-tert-butyl-2-
(1H-1,2,4-triazol-1-yl)-ethanone (1a) with aromatic aldehydes
in the presence of piperidine according to the literature procedure
[25]. 2,4-Dimethylthiazole-5-carbonyl chloride and 4-methyl-
1,2,3-thiadiazole-5-carbonyl chloride were synthesized accord-
ing to the reported methods [26,27], respectively. All of the
solvents and materials were reagent grade and purified as
required.
Table 1
Fungicidal activity of compounds 5 and 6 (relative inhibitory rate %).
Fusarium
oxysporium
Physalospora
piricola Nose
Alternaria
solani
Cercospora
arachidicola Hori
Gibberella
sanbinetti
Compounds
5a
5b
5c
6a
6b
6c
6d
6e
27.3
27.3
22.7
68.2
86.4
86.4
22.7
0.0
0.0
25.0
0.0
10.7
71.4
0.0
21.4
0.0
100
3.6
14.3
3.6
39.3
60.7
25.0
21.4
10.7
100
23.1
76.9
15.4
7.7
100.0
69.2
0.0
17.2
37.9
22.4
27.6
51.7
19.0
15.5
17.2
98.3
53.8
100
Difenoconazole
100
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H.-Y. Mao, H. Song, and D.-Q. Shi
Vol 49
General procedure for the synthesis of (Z)-1-tert-butyl
(or phenyl)-2-(1H-1,2,4-triazol-1-yl)-ethanone oximes 3 or
(1Z, 3Z)-4,4-dimethyl-1-substitutedphenyl-2-(1H-1,2,4-triazol-
temperature for 10–12 h till the reaction was complete
(monitored by TLC). The workup involved washing with
water and 5% NaHCO3, respectively. After phase separation,
drying over anhydrous sodium sulphate, filtration, and
evaporation, the crude product was purified by column
chromatography on silica gel using petroleum ether and
acetone (3:1 v/v) as the eluent, giving the target compounds 5
and 6 in 65–84% yields.
1-yl)-pent-1-en-3-one oximes 4.
To the stirred mixture of
1 or 2 (12.8 mmol), K2CO3 (2.33 g, 16.9 mmol) in anhydrous
methanol (20 mL) and hydroxylamine hydrochloride (1.08 g,
15.4 mmol) in H2O (6 mL) were added slowly at 0ꢂ5ꢁC. After
the addition completed, the solution was stirring under reflux for
8–10 h. The mixture was concentrated under vacuum, the
residue was poured to water (10 mL). The solid was collected
by filtration, and recrystallized from the mixture of methanol
and petroleum ether (V/V 1:1) to get 3 and 4 as a white solid.
Data for 5a (R = t-Bu): light yellow solid, yield: 65%, m.p.
129.5–130.6ꢁC; IR: C¼O 1742, C¼N 1526, 1506, C—O 1250,
1048, N—O—C 1033; 1H NMR (600 MHz, CDCl3): d 1.32(s, 9H,
t-Bu), 2.69 (s, 3H, CH3), 2.71 (s, 3H, CH3), 5.10 (s, 2H, CH2),
7.95 (s, 1H, triazole-H), 8.15 (s, 1H, triazole-H); ESI-MS:
m/z 343.5 (M+Na, 100), 322 (M+1, 5). Anal. Calcd for
C14H19N5O2S: C, 52.32; H, 5.96; N, 21.79. Found: C, 52.37; H,
5.71; N, 21.94.
Data for 5b (R = Ph): light yellow crystals, yield: 77%, m.p.
113.5–114.8ꢁC; IR: Ph-H 3098, 2961, C¼O 1754, Ph 1660,
1449, C¼N 1519, 1314, C—O 1244, 1194, N—O—C 1019;
1H NMR (600 MHz, CDCl3): d 2.75 (s, 3H, CH3), 2.78 (s, 3H,
CH3), 5.58 (s, 2H, CH2), 7.43–7.46 (m, 2H, ArH), 7.49–7.50
(m, 1H, ArH), 7.84 (d, J = 7.2 Hz, 2H, ArH), 7.95 (s, 1H, tria-
zole-H), 8.20 (s, 1H, triazole-H); ESI-MS: m/z 364 (M+Na,
100). Anal. Calcd for C16H15N5O2S: C, 56.29; H, 4.43; N,
20.51. Found: C, 56.05; H, 4.34; N, 20.30.
3,3-Dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one oxime
1
(3a). White solid, yield: 89%, m.p. 123.4–124.7 ꢁC; H NMR
(CDCl3, 400 MHz): d 1.17 (s, 9H, t-Bu), 5.05 (s, 2H, CH2),
7.91 (s, 1H, triazole-H), 8.31 (s, 1H, triazole-H), 9.41 (s, 1H,
OH). Anal. Calcd for C8H14N4O: C, 52.73; H, 7.74; N, 30.75.
Found: C, 52.57; H, 7.61; N, 30.53.
1-(Phenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone oxime (3b).
1
White solid, yield: 82%, m.p. 153.3–155.4ꢁC; H NMR (CDCl3,
400 MHz): d 5.56 (s, 2H, CH2), 7.42–7.81 (m, 5H, ArH), 7.93
(s, 1H, triazole-H), 8.16 (s, 1H, triazole-H), 9.38 (s, 1H, OH).
Anal. Calcd for C10H10N4O: C, 59.40; H, 4.98; N, 27.71. Found:
C, 59.25; H, 5.14; N, 27.90.
(1Z, 3Z)-1-(2,4-Dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-
Data for 5c (R = t-Bu): yellow solid, yield: 82%, m.p.
70.6–72.4ꢁC; IR: C¼O 1751, C¼N 1533, 1496, C—O 1245,
1052, N—O—C 1030; 1H NMR (600 MHz, CDCl3): d 1.36
(s, 9H, t-Bu), 2.98 (s, 3H, CH3), 5.12 (s, 2H, CH2), 7.95 (s, 1H,
triazole-H), 8.15 (s, 1H, triazole-H); ESI-MS: m/z 330.6
(M+Na, 100), 328 (48), 183 (55). Anal. Calcd for C12H16N6O2S:
C, 46.74; H, 5.23; N, 27.25. Found: C, 46.96; H, 5.28; N, 27.17.
triazol-1-yl)pent-1-en-3-one oxime (4a).
White solid, yield:
1
70%, m.p. 147.6–148.7ꢁC; H NMR (CDCl3, 400 MHz): d 1.17
(s, 9H, t-Bu), 6.36 (d, J = 9.0 Hz, 1H, ArH), 7.19 (d, J = 9.0 Hz,
1H, ArH), 7.45 (s, 1H, ArH), 7.48 (s, 1H, ¼CH), 7.89 (s, 1H,
triazole-H), 8.23 (s, 1H, triazole-H), 9.42 (s, 1H, OH). Anal.
Calcd for C15H16Cl2N4O: C, 53.11; H, 4.75; N, 16.52. Found:
C, 53.27; H, 4.78; N, 16.63.
Data for 6a (Ar = 4-ClC6H4): yellow crystals, yield: 84%, m.p.
133.0–133.8ꢁC; IR: Ph-H 3095, 2938, C¼O 1754, Ph 1588,
1485, 1433, C¼N 1510, C—O 1203, 1024, N—O—C 1001;
1H NMR (600 MHz, CDCl3): d 1.62 (s, 9H, t-Bu), 2.74 (s, 3H,
CH3), 2.78 (s, 3H, CH3), 7.36 (d, J = 8.4 Hz, 2H, ArH), 7.67
(s, 1H, ¼CH), 7.73 (d, J = 8.4 Hz, 2H, ArH), 8.10 (s, 1H,
triazole-H), 8.44 (s, 1H, triazole-H); ESI-MS: m/z 443
(M+, 100). Anal. Calcd for C21H22ClN5O2S: C, 56.81; H, 4.99;
N, 15.78. Found: C, 56.64; H, 5.07; N, 16.02.
(1Z, 3Z)-4,4-Dimethyl-1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-
1-yl)pent-1-en-3-one oxime (4b).
White solid, yield: 65%,
m.p. 119.5–120.5ꢁC; 1H NMR (CDCl3, 400 MHz): d 1.18
(s, 9H, t-Bu), 7.34 (d, J = 8.0 Hz, 2H, ArH), 7.50 (d, J = 8.0 Hz,
2H, ArH), 7.61 (s, 1H, ¼CH), 7.92 (s, 1H, triazole-H), 8.33
(s, 1H, triazole-H), 10.11 (s, 1H, OH). Anal. Calcd for
C15H17ClN4O: C, 59.11; H, 5.62; N, 18.38. Found: C, 59.02;
H, 5.49; N, 18.30.
(1Z, 3Z)-1-(4-Methoxyphenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-
Data for 6b (Ar = 2,4-Cl2C6H3): yellow crystals, yield:
75%, m.p. 117.5–118.4ꢁC; IR: Ph-H 3074, 2915, C¼O
1751, Ph 1545, 1438, 1407, C¼N 1524, C—O 1235, 1026,
N—O—C 1013; 1H NMR (600 MHz, CDCl3): d 1.59
(s, 9H, t-Bu), 2.74 (s, 3H, CH3), 2.79 (s, 3H, CH3), 7.27
(s, 1H, ¼CH), 7.29 (s, 1H, triazole-H), 7.34 (d, J = 9.0 Hz,
1H, ArH), 7.48 (s, 1H, ArH), 8.10 (d, J = 9.0 Hz, 1H,
ArH), 8.83 (s, 1H, triazole-H); ESI-MS: m/z 518 (M+K+2,
100), 516 (M+K, 78), 498 (M+Naꢀ1, 63). Anal. Calcd for
C21H21Cl2N5O2S: C, 52.72; H, 4.42; N, 14.64. Found: C,
52.59; H, 4.50; N, 14.71.
Data for 6c (Ar = 4-ClC6H4): yellow solid, yield: 73%, m.p.
131.1–133.3ꢁC; IR: Ph-H 3076, 2905, C¼O 1742, Ph 1562,
1465, 1372, C¼N 1524, C—O 1218, 1026, N—O—C 1017;
1H NMR (600 MHz, CDCl3): d 1.18 (s, 9H, t-Bu), 3.07 (s, 3H,
CH3), 7.47 (d, J = 8.4 Hz, 2H, ArH), 7.74 (d, J = 9.0 Hz, 2H,
ArH), 7.88 (s, 1H, ¼CH), 8.26 (s, 1H, triazole-H), 8.49 (s, 1H,
triazole-H); ESI-MS: m/z 452 (M+Naꢀ1, 15), 430.5 (M+, 100).
Anal. Calcd for C19H19ClN6O2S: C, 52.96; H, 4.44; N, 19.50.
Found: C, 52.73; H, 4.53; N, 19.37.
1-yl)pent-1-en-3-one oxime (4c).
White solid, yield: 79%,
m.p. 121.3–122.4ꢁC; 1H NMR (CDCl3, 400 MHz): d 1.19 (s, 9H,
t-Bu), 3.86 (s, 3H, OCH3), 6.97 (d, J = 7.6 Hz, 2H, ArH), 7.75
(d, J = 7.2 Hz, 2H, ArH), 7.83 (s, 1H, ¼CH), 7.91 (s, 1H,
triazole-H), 8.38 (s, 1H, triazole-H), 10.05 (s, 1H, OH).
Anal. Calcd for C16H20N4O2: C, 63.98; H, 6.71; N, 18.65.
Found: C, 63.83; H, 6.54; N, 18.77.
General procedure for the synthesis of (Z)-1-tert-butyl (or
phenyl)-2-(1H-1,2,4-triazol-1-yl)-ethanone O-[2,4-dimethylthiazole
(or 4-methyl-1,2,3-thiadiazole)-5-carbonyl] oximes 5 and
(1Z, 3Z)-4,4-dimethyl-1-substitutedphenyl-2-(1H-1,2,4-triazol-
1-yl)-pent-1-en-3-one O-[2,4-dimethylthiazole (or 4-methyl-
1,2,3-thiadiazole)-5-carbonyl] oximes 6.
Oxime 3 or 4
(2.0 mmol), triethylamine (2.4 mmol) and anhydrous chloroform
(7.5 mL) were added to a three-necked flask, a solution of
2,4-dimethylthiazole-5-carbonyl chloride [or 4-methyl-1,2,3-
thiadiazole)-5-carbonyl chloride] (2.2 mmol) in anhydrous
chloroform (5 mL) was added dropwise slowly at 5–10ꢁC.
After the addition completed, the mixture was stirred at room
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2012
Synthesis and Fungicidal Activity of (1Z, 3Z)-4,4-Dimethyl-1-substitutedphenyl-2-(1H-1,2,
515
4-triazol-1-yl)-pent-1-en-3-one O-[2,4-dimethylthiazole(or 4-methyl-1,2,3-thiadiazole)]-5-carbonyl Oximes
[3] Sheehan, D. J.; Hitchcock, C. A.; Sibley, C. M. Clin Microbiol
Rev 1999, 12, 40.
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Series 304; American Chemical Society: Washington, DC, 1986;
pp 25.
[5] Song, Z.; Nes, W. D. Lipids 2007, 42, 15.
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[7] Zhang, S.; Phadke, A.; Liu, C.; Wang, X.; Quinn, J.; Chen,
D.; Gadhachanda, V.; Li, S.; Deshpande, M. WO 2,006,122,011
(2006).
[8] Liu, C. L.; Li, L.; Li, Z. M. Bioorg Med Chem 2004, 12, 2825.
[9] (a) Alexander, R. P.; Aujla, P.; Batchelor, M. J.; Brookings,
D. C.; Buckley, G. M.; Crepy, K. V. L.; Kulisha, C. L.; Turner, J. P.
WO 2,006,114,606 (2006).
[10] Li, G.; Qian, X.; Cui, J.; Huang, Q.; Zhang, R.; Liu, F. J
Fluorine Chem 2006, 127, 182.
[11] Bakulev, V. A.; Dehaem, W. The Chemistry of 1,2,3-Thiadiazole;
Wiley: New York, 2004; pp 229.
[12] Tomlin, C. D. S. The Pesticide Manual, A World Compen-
dium,14th ed.; British Crop Production Council: Hampshire, 2006;
pp 11, 1042.
Data for 6d (Ar = 4-CH3OC6H4): white solid, yield: 78%, m.p.
116.0–116.6ꢁC; IR: Ph-H 3044, 2913, C¼O 1757, Ph 1549,
1450, 1351, C¼N 1545, C—O 1229, 1024, N—O—C 1026;
1H NMR (600 MHz, CDCl3): d 1.65 (s, 9H, t-Bu), 3.06 (s, 3H,
CH3), 3.88 (s, 3H, OCH3), 6.98 (d, J = 7.2 Hz, 2H, ArH), 7.74
(d, J = 7.2 Hz, 2H, ArH), 7.90 (s, 1H, ¼CH), 8.25 (s, 1H,
triazole-H), 8.45 (s, 1H, triazole-H); ESI-MS: m/z 428 (7),
426 (M+, 100). Anal. Calcd for C20H22N6O3S: C, 56.32; H,
5.20; N, 19.70. Found: C, 56.41; H, 5.35; N, 19.84.
Data for 6e (Ar = 2,4-Cl2C6H3): yellow crystals, yield:
69%, m.p. 102.2–103.8ꢁC; IR: Ph-H 3042, 2915, C¼O 1760,
Ph 1536, 1440, C¼N 1526, C—O 1234, 1045, N—O—C
1
1024; H NMR (600 MHz, CDCl3): d 1.17 (s, 9H, t-Bu), 2.87
(s, 3H, CH3), 6.95 (d, J = 9.0 Hz, 1H, ArH), 7.17 (d, J = 7.2 Hz,
1H, ArH), 7.36 (s, 1H, ArH), 7.46 (s, 1H, ¼CH), 7.79 (s, 1H,
triazole-H), 8.13 (s, 1H, triazole-H); ESI-MS: m/z 505 507
(M+K+2, 65), (M+K, 100), 486 (M+Naꢀ1, 8), 384 (26).
Anal. Calcd for C19H18Cl2N6O2S: C, 49.04; H, 3.90; N, 18.06.
Found: C, 49.23; H, 3.77; N, 18.18.
Fungicidal activity testing. The fungicidal activity measurement
method was adapted from the one described by Molina Torres [28].
The synthesized target compounds were dissolved in 0.5–1.0 mL of
DMF to the concentration of 1000 mg/L. The solutions (1 mL) were
mixed rapidly with thawed potato glucose agar culture medium
(9 mL) under 50ꢁC. The mixtures were poured into Petri dishes.
After the dishes were cooled, the solidified plates were incubated
with 4-mm mycelium disk, inverted, and incubated at 28ꢁC for 48 h.
Distilled water was used as the blank control and the commercially
available fungicide difenoconazole as the control drug. Three
replicates of each test were carried out. The mycelial elongation
radius (mm) of fungi settlements was measured after 48 h of culture.
The growth inhibitory rates were calculated with the following
equation: I = [(C ꢀ T)/C] × 100%. Here, I is the growth inhibitory
rate (%), T is the treatment group fungi settlement radius (mm), and
C is the radius of the blank control. The results are listed in Table 1.
[13] Tomlin, C. D. S. The Pesticide Manual, A World Compen-
dium, 14th ed.; British Crop Production Council: Hampshire, 2006;
pp 694, 1025.
[14] Song, B. A.; Liu, X. H.; Yang, S.; Hu, D. Y.; Jin, L. H.; Zhang,
Y. T. Chin J Org Chem 2005, 25, 507.
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Takao, H.; Wakisaka, S.; Murai, K. Chem Abstr 1995, 122, 160634a.
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Pestic Sci 1997, 51, 109.
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2002, 4, 23.
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[19] Tomlin, C. D. S. The Pesticide Manual, A World Compen-
dium, 14th Ed.; British Crop Production Council: Hampshire, 2006;
pp 911–912.
[20] Huang, R.-Q.; Sun, J.-Y.; Ma, J.-A.; Li, H.-Y. Chin J Appl
Chem 1998, 15, 9.
[21] Chen, M.; Zhang, H.; Liao, L.; Guo, Q.; Wang, J. J. Xiamen
Univ (Nat Sci) 1994, 33, 499.
Acknowledgments. This work was supported by the Natural
Science Foundation of China (No. 20872046) and the Natural
Science Foundation of Hubei Province (No. 2008CDB086).
[22] Liao, L.; Zhang, H.; Chen, M.; Zhang, L.; Guo, Q. J. Xiamen
Univ (Nat Sci) 1997, 36, 575.
[23] Yang, S.; Song, B. A.; Li, Z. M.; Liao, R. A. Chin J Pestic Sci
2002, 4, 23.
[24] Meng, L.; Shi, D. Q. Chin J Struct Chem 2009, 28, 307.
[25] Xia, H. Y.; Duan, X. Z.; Tu, Y. M.; Liu, J. F. Chin Pestic Sci
2001, 40, 12.
REFERENCES AND NOTES
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[28] Molina-Torres, J.; Salazar-Cabrera, C. J.; Armenta-Salinas, C.;
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet