Design, synthesis, and herbicidal activities of 3-aryl-4-substituted-5-[3- (trifluoromethyl)phenoxy]-1,2,4-triazoles

Article abstract of DOI:10.1002/jhet.1920

In order to find novel bleaching herbicide lead compounds, a series of novel 3-aryl-4-substituted-5-[3-(trifluoromethyl)phenoxy]-1,2,4-triazoles were designed and synthesized by the multi-step reactions. N-(Arylformamido) phenylthioureas undergo ring clos

Full text of DOI:10.1002/jhet.1920

Month 2014
Design, Synthesis, and Herbicidal Activities of 3-Aryl-4-substituted-5-
[3-(trifluoromethyl)phenoxy]-1,2,4-triazoles
*
Man-Yun Liu and De-Qing Shi
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal
University, Wuhan 430079, Hubei, People’s Republic of China
*
E-mail: chshidq@mail.ccnu.edu.cn
Received September 26, 2012
DOI 10.1002/jhet.1920
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
N
N
N
N
S
(1) NaOH
(2) H3O
Me2SO4
KOH
Ar
Ar
ArCONHNHCNHR
SCH3
N
SH
N
R
R
2
1
CF3
N
N
N
N
HO
H2O2/Na2WO4
O
CF3
Ar
Ar
O
N
R
SCH3
O
N
R
HOAc or DMF
K2CO3/DMF
4a~4k
3
In order to find novel bleaching herbicide lead compounds, a series of novel 3-aryl-4-substituted-5-[3-
(trifluoromethyl)phenoxy]-1,2,4-triazoles were designed and synthesized by the multi-step reactions.
N-(Arylformamido)phenylthioureas undergo ring closure in the presence of sodium hydroxide to generate
3-aryl-4-substituted-4H-[1,2,4]triazol-5-thiols 1, which reacted with methyl sulfate in the presence of
K2CO3 to give 3-aryl-5-methylsulfanyl-4-substituted-4H-[1,2,4]triazoles 2. The target compounds 4 were
synthesized by the oxidation of 2 in the presence of H2O2 and Na2WO4, followed by the substitution with
3-(trifluoromethyl)phenol in moderate to good yields. Their structures were confirmed by IR, 1H NMR, EI–MS,
and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate to good
selective herbicidal activity against Brassica campestris L at the concentration of 100mg/mL. Compounds
4c and 4i possessed 75.0% and 82.6% inhibition against Brassica campestris L at the concentration of
100 mg/mL. However, the target compounds 4 showed weak herbicidal activity against Echinochloa crus-galli
at the concentration of 100 and 10mg/mL.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
order to find novel bleaching herbicide lead compounds,
according to bioisosterism, using PDS inhibitor A as the lead
compound (Fig. 2), a series of novel 3-aryl-4-substituted-5-
[3-(trifluoromethyl)phenoxy]-1,2,4-triazoles 4a–4k were
designed and synthesized by replacing 1,2,4-thiadiazole of
PDS inhibitor A with 1,2,4-triazole. Herein, we would like
to report the synthesis and herbicidal activities of the title
compounds 4 in this paper (Scheme 1).
Phytoene desaturase (PDS) is a key enzyme for photo-
synthetic apparatus of green plants. When PDS is inhibited
by its inhibitor, a lack of carotenoid synthesis may lead to
typical bleaching symptoms, tissues blight, and death in
plants. So, the PDS inhibitors are used as a kind of impor-
tant bleaching herbicides [1–4]. Among them, Norflurazon,
Fluridone Flurochloridone, Diflufenican and Picolinafen are
commercially PDS herbicides that are used widely in mod-
ern agriculture (Fig. 1), and compounds A and B showed
the strongest inhibitory activity against PDS with IC50 of
1*10À9–1*10À8 M[5]. The study of structure-activity
relationships showed that PDS inhibitors usually possess a
central five-membered or six-membered heterocycle
containing one or two substituted phenyl rings, in which a
3-trifluoromethylphenyl group is a common structure in all
inhibitors (Fig. 1). On the other hand, most of pesticide
and drug skeletons contain pyridine and 1,2,4-triazole
moiety because pyridine and 1,2,4-triazole derivatives
possessed a wide range of biological activities, such as
insecticidal, herbicidal, and fungicidal activities [6–8]. In
RESULTS AND DISCUSSION
3-Aryl-4-substituted-5-[3-(trifluoromethyl)phenoxy]-1,2,
4-triazoles were synthesized by the multi-step reactions.
N-(Arylformamido)phenylthioureas undergo ring closure in
the presence of NaOH to generate 3-aryl-4-substituted-4H-
[1,2,4]triazol-5-thiols 1, which reacted with methyl sulfate
in the presence of K2CO3 to give 3-aryl-5-methylsulfanyl-
4-substituted-4H-[1,2,4]triazoles 2. The target compounds
4 were synthesized by the oxidation of 2 in the presence
of H2O2 and Na2WO4, followed by the substitution with 3-
(trifluoromethyl)phenol in moderate to good yields.
© 2014 HeteroCorporation

M.-Y. Liu and D.-Q. Shi
Vol 000
Figure 1. Some commercial phytoene desaturase (PDS) inhibitors and high activity PDS inhibitors.
targets, oil rape and barnyard grass, at concentrations of 100
and 10 mg/mL, according to the reported method [9]. The
results showed that these compounds exhibited moderate
selective herbicidal activity against oil rape at the
concentration of 100 mg/mL. For example, compounds 4c
and 4i possessed 75.0 and 82.6% inhibition against
Brassica campestris L at the concentration of 100 mg/mL.
However, they displayed weak herbicidal activity
against Echinochloa crus-galli at the concentration of
100 and 10 mg/mL. As for the preliminary structure-
activity relationships, firstly, compound 4i showed the
best herbicidal activity against 4j and did not displayed
Figure 2. Molecular design using A as the lead compound by replacing
1,3,4-thiadiazole with 1,2,4-triazole. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com].
Their structures were deduced from their spectral
1
data (IR, H NMR, and EI–MS) and elemental analyses,
herbicidal activity against B campestris
L
at the
which were listed in the experimental section. In the IR
spectra of 4, the presence of the signals ca 3050 and
1650–1450 cmÀ1 indicated the existence of Ar group, the
signal 1325 cmÀ1 is attributed to C–F absorption, and the
peak of 1225–1260 cmÀ1 is attributed to C–O–C absorption
concentration of 100 mg/mL. Secondly, aromatic group at 3-
position has some effects on their herbicidal activities, those
compounds when Ar is 3-pyridyl displayed better activity
than those when Ar is 4-pyridyl did, and compounds when
Ar is phenyl exhibited the weakest herbicidal activity.
Further exploring of structure-activity relationships needs
more experimental results to support. Further biological
activity (in vivo) investigations are on the way.
In conclusion, a series of novel 3-aryl-4-substituted-5-[3-
(trifluoromethyl)phenoxy]-1,2,4-triazoles were designed and
synthesized by the multi-step reactions. The preliminary
bioassay indicated that some of them displayed moderate to
1
band. In the H NMR spectra of 4, the aromatic protons
appeared in the chemical shift d 7.0–8.6. The EI mass spec-
trum of 4 shows strong molecular ion peak and anticipated
fragmentation ion peaks, which were in good accordance
with the given structures of products 4.
Herbicidal activity. The preliminary herbicidal activities
of compounds 4 were evaluated, against two representative
Scheme 1. The synthetic route of the target compounds 4a–4k.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Design, Synthesis, and Herbicidal Activities of 3-Aryl-4-substituted-5-
[3-(trifluoromethyl)phenoxy]-1,2,4-triazoles
DMF (20 mL) were added to a 100 mL three-necked flask, the
mixture were stirred at 40–50ꢀC, whereas the solution of 30%
H2O2 (4.5 g, 40 mmol) in ethanol (5 mL) was added dropwise
slowly, after the addition was complete, the mixture was stirred
at 60ꢀC for 3 h (monitored by TLC). After most of solvents
were removed in vacuum, the residue was poured into water
(100 mL), the solid formed was filtered by suction, the
crude product was recrystallized by using the mixture of
DMF and H2O (1:1) to give 3h as white solid in 85% yields,
mp 207–208ꢀC.
good selective herbicidal activity against B campestris L at
the concentration of 100 mg/mL. However, the target com-
pounds 4 showed weak herbicidal activity against E crus-galli
at the concentration of 100 and 10 mg/mL.
EXPERIMENTAL
Melting points were determined with a WRS-1B digital melting
1
point apparatus (Shanghai, China) and are uncorrected. H NMR
1H NMR (600 MHz, CDCl3): d 3.55 (s, 3H), 7.28–7.30
(m, 1H), 7.41 (d, J= 7.2 Hz, 2H), 7.54 (t, J= 7.8 Hz, 2H), 7.58–7.60
(m, 1H), 7.78 (t, J = 7.8 Hz, 1H), 8.64–8.66 (m, 2H). Anal. calcd
for C14H12N4O2S: C, 55.99; H, 4.03; N, 18.65. Found: C, 55.75;
spectra were recorded with a Varian Mercury PLUS 400
(400 MHz) or Varian Mercury PLUS 600 (600MHz) spectrometer
(Palo Alto, CA, USA) with TMS as the internal reference and
CDCl3 as the solvent, chemical shift in parts per million (d ppm)
form an internal standard [tetramethylsilane (TMS) or chloroform
(CHCl3)], multiplicity (s = singlet, d =doublet, t =triplet, q =quartet,
and m = multiplet), integration, and coupling constant (Hz).
Although mass spectra were measured on a Finnigan Trace MS
2000 spectrometer (Finnigan Cooperation, CA, USA) at 70 eV using
EI method. IR spectra were measured by a Nicolet NEXUS 470
spectrometer (Thermo Nicolet Corporation, USA). Elemental
analyses were performed with an Elementar Vario ELШ CHNSO
elemental analyzer (Elementar Cooperation, Germany). N-
(Arylformamido)phenylthioureas, 3-aryl-4-substituted-1,2,4-triazol-
5-thiol 1 were prepared according to the reported methods [10–12],
respectively.
H, 3.94; N, 18.50.
Other compounds 3 can be synthesized in the similar procedure
and can be used in the next reaction directly without further
structure characterization.
General procedure for the synthesis of 3-aryl-4-substituted-
5-[3-(trifluoromethyl)phenoxy]-1,2,4-triazoles 4a–4k. 3-Aryl-
4-substituted-5-methylsulfonyl-1,2,4-triazole 3 (4.5 mmol), 3-
(trifluoromethyl)phenol (5.4mmol, 0.87g), K2CO3 (5.4mmol,
0.75g), and DMF (15mL) were added to a 50mL three-necked
flask, and the mixture was allowed to be stirred at 80–85ꢀC for
2–3 h (monitored by TLC). The reaction mixture was poured
into iced water (100 mL), the solid was filtered and washed with
water (15 mL*3), and recrystallized using the mixture of C2H5OH
and H2O (1:1) to give 4 as white solid in 74–91% yields.
Data for 4a (Ar = 4-pyridyl, R = C6H5). White solid, yield:
Synthesis of 3-(4-pyridyl)-4-phenyl-5-methylthio-1,2,4-triazole
2a[13].
3-(4-pyridyl)-4-phenyl-1,2,4-triazol-5-thiol 1 (1.91 g,
7.5 mmol), aqueous KOH (0.3 M, 60mL) were added to a 100 mL
three-necked flask, the solution of Me2SO4 (1.1mL, 11.2mmol)
in ethanol (5 mL) was added dropwise slowly at 0–5ꢀC; after the
addition was complete, the mixture was stirred at room
temperature for 0.5–1 h. The solid was filtered by suction and
washed with water (5mL*3). 2a was obtained as white solid in
81% yield, mp 138–140ꢀC.
1
86%, mp 119–120ꢀC; H NMR (CDCl3, 400 MHz) d: 7.33–7.34
(m, 4H), 7.50 (d, J = 5.2 Hz, 1H), 7.54 (t, J = 5.6 Hz, 1H), 7.57
(t, J = 5.2 Hz, 3H), 7.63 (s, 1H), 7.66 (d, J = 5.6 Hz, 1H), 8.58
(d, J = 4.0 Hz, 2H); IR (KBr) υ: 3075, 3039 (ArH), 1602,
1530, 1498, 1444 (Ar), 1326 (C–F), 1202, 1118 (C–O–C) cmÀ1
;
EI–MS (70 eV) m/z (%): 382 (M+, 27.3), 365 (25.7), 313 (13.4),
300 (17.1), 299 (15.1), 181 (10.0), 145 (17.2), 118 (17.9), 117
(100), 91 (12.6), 77 (49.8). Anal. calcd for C20H13F3N4O: C
62.83, H 3.43, N 14.65; found C 62.75, H 3.31, N 14.70.
Data for 4b (Ar = 4-pyridyl, R = 4-CH3-C6H4). White solid,
1H NMR (600 MHz, CDCl3): d 2.74 (s, 3H), 7.24–7.26 (m,
3H), 7.52–7.54 (m, 3H), 7.80 (d, J = 7.8 Hz, 1H), 8.56 (d,
J = 4.2 Hz, 1H), 8.59 (s, 1H). Anal. calcd for C14H12N4S: C,
62.66; H, 4.51; N, 20.88. Found: C, 62.82; H, 4.38; N, 20.60.
Other compounds 2 can be synthesized in the similar procedure.
2b (Ar = 4-pyridyl, R = 4-CH3-C6H4), white solid, mp 149–150ꢀC,
yield: 89%. 1H NMR (400 MHz, CDCl3): d 2.47 (s, 3H), 2.74
(s, 3H), 7.13 (d, J = 7.2 Hz, 2H), 7.31–7.35 (m, 4H), 8.54
(d, J = 4.8 Hz, 2H). Anal. calcd for C15H14N4S: C, 63.80; H, 5.00;
N, 19.84. Found: C, 63.61; H, 4.94; N, 19.69.
1
yield: 79%, mp 57–58ꢀC; H NMR (CDCl3, 600 MHz) d: 2.48
(s, 3H), 7.20 (d, J = 7.8 Hz, 2H), 7.34–7.36 (m, 4H), 7.49
(d, J = 7.2 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.61 (s, 1H), 7.65
(d, J = 7.8 Hz, 1H), 8.58 (d, J = 4.2 Hz, 2H); IR (KBr) υ:
3081, 3041 (ArH), 1576, 1535, 1497, 1450 (Ar), 1324 (C–F),
1180, 1126 (C–O–C) cmÀ1; EI–MS (70 eV) m/z (%): 397
(M + 1, 20.5), 396 (M+, 90.8), 379 (49.8), 327 (16.9), 195
(13.5), 159 (17.0), 145 (25.2), 132 (12.0), 131 (100), 129
(30.0), 104 (25.6), 91 (52.8), 77 (36.5), 65 (38.4). Anal. calcd for
C21H15F3N4O: C 63.63, H 3.81, N 14.14; found C 63.47, H 3.86,
N 14.03.
2c (Ar = 3-pyridyl, R = 4-CH3O-C6H4), white solid, mp
1
163–164ꢀC, yield: 92%. H NMR (600MHz, CDCl3): d 2.74 (s,
3H), 3.87 (s, 3H), 7.00 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 9.0 Hz,
2H), 7.25 (t, J = 9.0 Hz, 1H), 7.85 (d, J = 7.8 Hz, 1H), 8.57 (d,
J = 6.6 Hz, 1H), 8.60 (s, 1H). Anal. calcd for C15H14N4OS: C,
60.38; H, 4.73; N, 18.78. Found: C, 60.22; H, 4.86; N, 18.50.
2i (Ar = 3-pyridyl, R = 4-CH3-C6H4), white solid, mp 172–
Data for 4c (Ar = 4-pyridyl, R = 4-CH3O-C6H4).
White
solid, yield: 84%, mp 111–112ꢀC; 1H NMR (CDCl3,
600 MHz) d: 3.90 (s, 3H), 7.04 (d, J = 8.4 Hz, 2H), 7.23 (d,
J = 9.0 Hz, 2H), 7.36 (d, J = 6.0 Hz, 2H), 7.48 (d, J = 7.8 Hz,
1H), 7.52 (t, J = 8.4 Hz, 1H), 7.61 (s, 1H), 7.66 (d, J = 8.4 Hz,
1H), 8.59 (s, 2H); IR (KBr) υ: 3071, 3052 (ArH), 1565, 1531,
1492, 1456 (Ar), 1326 (C–F), 1176, 1124 (C–O–C) cmÀ1; EI–
MS (70 eV) m/z (%): 413 (M + 1, 9.4), 412 (M+, 36.3), 411
(15.3), 395 (14.2), 343 (7.5), 207 (10.0), 148 (12.7), 147
(100), 121 (10.5), 92 (21.2), 77 (18.5), 57 (10.3). Anal. calcd
for C21H15F3N4O2: C 61.17, H 3.67, N 13.59; found C 61.23,
H 3.54, N 13.71.
1
173ꢀC, yield: 95%. H NMR (400 MHz, CDCl3): d 2.44 (s, 3H),
2.74 (s, 3H), 7.12 (d, J = 8.4 Hz, 2H), 7.24–7.32 (m, 3H), 7.85 (d,
J = 5.6 Hz, 1H), 8.56–8.58 (m, 2H). Anal. calcd for C15H14N4S:
C, 63.80; H, 5.00; N, 19.84. Found: C, 63.95; H, 5.06; N, 19.71.
Other compounds 2 can be synthesized according to the similar
procedure and can be used in the next reaction directly without
further structure characterization.
Synthesis of 3-(3-pyridyl)-4-phenyl-5-methylsulfonyl-1,2,
4-triazole 3h[14].
3-(3-pyridyl)-4-phenyl-5-methylthio-1,2,4-
triazole 2h (2.68 g, 10 mmol), Na2WO4 (2 mmol, 0.66 g), and
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M.-Y. Liu and D.-Q. Shi
Vol 000
Data for 4d (Ar = 4-pyridyl, R = 2-CH3-C6H4). White solid,
1538, 1495, 1452 (Ar), 1327 (C–F), 1181, 1122 (C–O–C) cmÀ1
.
yield: 80%, mp 116–117ꢀC; 1H NMR (CDCl3, 600 MHz) d: 2.13
(s, 3H), 7.27 (d, J = 7.2 Hz, 1H), 7.32 (d, J = 6.0 Hz, 2H), 7.41
(t, J = 6.6 Hz, 1H), 7.44 (t, J = 7.8 Hz, 1H), 7.52 (t, J = 6.6 Hz,
1H), 7.54 (t, J = 7.8 Hz, 2H), 7.60 (s, 1H), 7.64 (d, J = 7.8 Hz,
1H), 8.55 (d, J = 5.4 Hz, 2H); IR (KBr) υ: 3083, 3045
(ArH), 1573, 1540, 1492, 1456 (Ar), 1321 (C–F), 1176, 1124
(C–O–C) cmÀ1; EI–MS (70 eV) m/z (%): 397 (M + 1, 11.8), 396
(M+, 51.7), 395 (13.7), 381 (13.5), 379 (14.1), 378 (11.1), 236
(13.1), 235 (100), 207 (18.6), 195 (16.4), 165 (11.8), 160
(39.6), 131 (57.0), 104 (42.8), 91 (65.2), 77 (43.5), 65 (51.5).
Anal. calcd for C21H15F3N4O: C 63.63, H 3.81, N 14.14; found
C 63.81, H 3.65, N 14.30.
Anal. calcd for C21H14F3N3O: C 66.14, H 3.70, N 11.02; found
C 66.01, H 3.59, N 11.25.
Data for 4k (Ar = C6H5, R = 4-CH3O-C6H4). White solid,
yield: 74%, mp 109–110ꢀC; 1H NMR (CDCl3, 400 MHz) d:
3.85 (s, 3H), 6.98 (t, J = 4.8 Hz, 2H), 7.19 (t, J = 4.8 Hz, 2H),
7.31–7.38 (m, 3H), 7.46–7.51 (m, 4H), 7.60 (s, 1H), 7.65
(d, J = 7.2 Hz, 1H); IR (KBr) υ: 3075, 3045 (ArH), 1566, 1535,
1492, 1454 (Ar), 1325 (C–F), 1175, 1126 (C–O–C) cmÀ1. Anal.
calcd for C22H16F3N3O2: C 64.23, H 3.92, N 10.21; found C
64.37, H 3.76, N 10.30.
Herbicidal activity (in vitro). The herbicidal evaluation of
compounds 4 was carried out in the laboratory of biological
activities test, State Key Laboratory of Elemento-organic
Chemistry, Nankai University, China. Compounds 4 were
determined with B campestris L. and E. crus-galli as samples of
annual dicotyledonous and monocotyledonous plants,
respectively, using a previously reported procedure [9]. For all
of the bioassay tests, each treatment was repeated twice.
Data for 4e (Ar = 4-pyridyl, R = benzyl). White solid, yield:
75%, mp 110–111ꢀC; 1H NMR (CDCl3, 600 MHz) d: 5.27
(s, 2H), 7.11 (d, J = 6.6 Hz, 2H), 7.35–7.38 (m, 3H), 7.50–7.54
(m, 4H), 7.62 (s, 1H), 7.66 (d, J = 7.8 Hz, 1H), 8.72 (d, J = 6.0 Hz,
2H); IR (KBr) υ: 3086, 3058 (ArH), 1567, 1535, 1494, 1452 (Ar),
1324 (C–F), 1172, 1127 (C–O–C)cmÀ1
. Anal. calcd for
C21H15F3N4O: C 63.63, H 3.81, N 14.14; found C 63.48, H 3.70,
N 14.29.
Treatment.
The emulsions of purified compounds were
prepared by dissolving them in N,N-dimethylformamide
(100 mL) with the addition of Tween 20 (2 mL). The mixture of
the same amount of water, N,N-dimethylformamide, and Tween
20 was used as control. The commercially available herbicide,
Bispyribac-sodium was used as a compared sample to evaluate
the herbicidal activity.
Inhibition of the root-growth of rape (B. campestris L.).
Rape seeds were soaked in distilled water for 4 h before being
placed on a filter paper in a 6 cm Petri plate, to which 2 mL of
inhibitor solution had been added in advance. Usually, 10 seeds
were used on each plate. The plate was placed in a dark room
and allowed to germinate for 72 h at 28 Æ 1ꢀC. The lengths of
10 rape roots selected from each plate were measured, and the
means were calculated. The percentage inhibition was used to
describe the control efficiency of the compounds. The herbicidal
activity was listed in Table 1.
Data for 4f (Ar = 4-pyridyl, R = 2,4,6-(CH3)3-C6H2). White
1
solid, yield: 82%, mp 192–194ꢀC; H NMR (CDCl3, 400 MHz)
d: 1.94 (s, 9H), 6.98–7.03 (m, 2H), 7.19 (d, J = 6.0 Hz, 2H),
7.28 (d, J = 7.2 Hz, 1H), 7.43 (d, J = 7.2 Hz, 1H), 7.48
(t, J = 7.8 Hz, 1H), 7.56–7.58 (m, 1H), 8.52 (d, J = 6.0 Hz, 2H);
IR (KBr) υ: 3076, 3051 (ArH), 1577, 1545, 1487, 1452 (Ar), 1325
(C–F), 1168, 1126 (C–O–C)cmÀ1. Anal. calcd for C23H19F3N4O:
C 65.09, H 4.51, N 13.20; found C 65.22, H 4.64, N 13.06.
Data for 4g (Ar = 4-pyridyl, R = 4-Cl-C6H4). Yellow solid,
yield: 78%, mp 160–161ꢀC; 1H NMR (CDCl3, 400 MHz) d:
7.29 (d, J = 7.6 Hz, 2H), 7.35 (d, J = 7.6 Hz, 2H), 7.53–7.56
(m, 4H), 7.64–7.68 (m, 2H), 8.62 (d, J = 5.2 Hz, 2H); IR (KBr)
υ: 3074, 3056 (ArH), 1535, 1498, 1452 (Ar), 1324 (C–F), 1178,
1126 (C–O–C) cmÀ1. Anal. calcd for C20H12ClF3N4O: C 57.64,
H 2.90, N 13.44; found C 57.82, H 2.97, N 13.65.
Data for 4h (Ar = 3-pyridyl, R = C6H5). White solid, yield:
91%, mp 100–101ꢀC; 1H NMR (CDCl3, 400 MHz) d: 7.30–7.32
(m 3H), 7.50 (d, J = 6.0 Hz, 1H), 7.53–7.56 (m, 4H), 7.63
(s, 1H), 7.67 (d, J = 4.8 Hz, 1H), 7.85 (d, J = 6.0 Hz, 1H), 8.62
(s, 2H); IR (KBr) υ: 3089, 3060 (ArH), 1498, 1451 (Ar), 1323
(C–F), 1206, 1175, 1125 (C–O–C)cmÀ1; EI–MS (70 eV) m/z
(%): 382 (M+, 86.7), 381 (100), 365 (24.7), 237 (10.9), 194
(10.3), 181 (18.8), 180 (20.6), 145 (39.2), 125 (17.4), 117 (81.5),
95 (20.5), 77 (77.2), 65 (86.5). Anal. calcd for C20H13F3N4O: C
62.83, H 3.43, N 14.65; found C 62.96, H 3.51, N 14.54.
Data for 4i (Ar = 3-pyridyl, R = 4-CH3-C6H4). White solid,
yield: 85%, mp 61–62ꢀC; 1H NMR (CDCl3, 600 MHz) d: 2.44
(s, 3H), 7.10 (d, J= 8.4 Hz, 1H), 7.19 (d, J= 8.4 Hz, 2H), 7.32 (d,
J= 7.2 Hz, 2H), 7.49 (d, J= 6.6 Hz, 1H), 7.52 (d, J= 6.6 Hz, 1H),
7.60 (t, J= 7.2 Hz, 1H), 7.66 (d, J= 7.2 Hz, 1H), 7.90 (t, J=6.6Hz,
1H), 8.60 (s, 2H); IR (KBr) υ: 3072, 3043 (ArH), 1572, 1538,
1495, 1452 (Ar), 1327 (C–F), 1181, 1122 (C–O–C) cmÀ1; EI–MS
(70 eV) m/z (%): 397 (M + 1, 16.0), 396 (M+, 100), 395 (92.8), 379
(10.8), 281 (10.2), 259 (10.1), 235 (10.9), 208 (13.0), 195 (21.8),
194 (12.8), 145 (23.9), 131 (71.8), 129 (10.5), 104 (26.0), 91
(52.2), 77 (48.5), 65 (47.3). Anal. calcd for C21H15F3N4O: C
63.63, H 3.81, N 14.14; found C 63.80, H 3.97, N 14.33.
Inhibition of the seedling growth of barnyard grass
(E. crus-galli).
Ten E. crus-galli seeds were placed into a
50mL cup covered with a layer of glass beads and a piece of filter
paper at the bottom, to which 6 mL of inhibitor solution had been
Table 1
Herbicidal activity of compounds 4a–4k (growth inhibition rate %).
Brassica campestris
Echinochloa
root test
crus-galli cup test
Compound
10 mg/mL 100 mg/mL 10 mg/mL 100 mg/mL
4a
4b
4c
4d
4e
4f
4g
4h
24.2
37.2
21.6
12.0
0
0
0
13.6
59.4
0
47.0
60.4
75.0
23.8
35.8
22.8
41.6
63.6
82.6
0
0
0
0
0
0
0
0
0
0
0
5.0
20.0
5.0
0
10.0
10.0
5.0
0
4i
4j
0
0
Data for 4j (Ar = C6H5, R = C6H5). White solid, yield: 76%,
1
4k
13.6
65.6
56.6
69.8
0
46.9
5.0
72.4
mp 112–113ꢀC; H NMR (CDCl3, 400 MHz) d: 7.27–7.32 (m,
Bispyribac-
sodium
4H), 7.38 (d, J = 7.2 Hz, 2H), 7.43–7.53 (m, 6H), 7.62 (s, 1H),
7.66 (d, J = 7.6 Hz, 1H); IR (KBr) υ: 3072, 3043 (ArH), 1572,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Design, Synthesis, and Herbicidal Activities of 3-Aryl-4-substituted-5-
[3-(trifluoromethyl)phenoxy]-1,2,4-triazoles
added in advance. The cup was placed in a bright room, and the
seeds were allowed to germinate for 72h at 28Æ 1ꢀC. The heights
of the above-ground parts of the seedlings in each cup were
measured, and the means were calculated. The percentage
inhibition was used to describe the control efficiency of the
compounds. The herbicidal activity is listed in Table 1.
Baker, D. A., Fenyes, J. G., Moberg, W. K., Cross, B., Eds.; ACS
Symposium Series, Vol. 584, American Chemical Society: Washington,
DC, 1995; pp 161–170.
[4] Sandmann, G.; Kowalczyk-Schröder, S.; Taylor, H. M.;
Böger, P. Pest Biochem Physiol 1992, 42, 1.
[5] Laber, B.; Usunow, G.; Wiecko, E.; Franke, W.; Franke, H.;
Köhn, A. Pest Biochem Physiol 1999, 63, 173.
[6] Elbert, A.; Becker, B.; Hartwig, J.; Erdelen, C. Pflanzenschutz-
Nachrichten Bayer 1991, 44, 113.
[7] Ashton, I. A.; Abulnaja, K. O.; Pallett, K. E.; Cole, D. J.;
Harwood, J. L. Phytochemistry 1994, 35, 587.
[8] Karadimos, D. A.; Karaoglanidis, G. S.; Tzavella–Klonari, K.
Crop Prot 2005, 24, 23.
Acknowledgments. This work was supported by the Natural Science
Foundation of China (No. 20872046) and the Natural Science
Foundation of Hubei Province (No. 2008CDB086).
[9] (a) Yu, Z. H.; Shi, D. Q. Phosphorus Sulfur and Silicon, 2010,
185, 1746; (b) Tang, W.; Yu, Z. H.; Shi, D. Q. Heteroatom Chem 2010,
21, 148.
REFERENCES AND NOTES
[10] Demirbas, N.; Karaoglu, S. A.; Demirbas, A.; Sancak, K. Eur J
Med Chem 2004, 39, 793.
[11] Qin, Z. H.; Li, M. L.; Wang, M. A. Chin J Pest Sci 1999,
1, 25.
[1] Sandmann, G.; Böger, P. Phytoene desaturase as a target for
bleaching herbicides. In Herbicide Activity: Toxicology, Biochemistry,
and Molecular Biology; Roe, R. M., Burton, J. D., Kuhr, R. J., Eds.;
IOS Press: Amsterdam, 1997; pp 1–10.
[2] Sandmann, G. Bleaching herbicides: action mechanism in
carotenoid biosynthesis, structural requirements, and engineering of
resistance. In Herbicidal Classes in Development: Mode of Action, Targets,
Genetic Engineering, Chemistry; Böger, P., Wakabayashi, K., Hirai, K.,
Eds.; Springer: Berlin, 2002; pp 43–55.
[12] Bayrak, H.; Demirbas, A.; Karaoglu, S. A.; Demirbas, N. Eur J
Med Chem 2009, 44, 1057.
[13] Zhang, Z.; Yang, K. Youji Huaxue 1988, 8, 131.
[14] Holsworth, D.; Waaler, J.; Machon, O.; Krauss, S. Triazole
derivatives as Wtn pathway inhibitors and their preparation and use in the
treatment of diseases affected by Wnt signaling pathway over-activation.
WO 2010139966, 2010.
[3] Mitchell, G. Phytoene desaturase. A model for the optimiza-
tion of inhibitors. In Synthesis and Chemistry of Agrochemicals IV,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet