Structure-activity relationship development of dihaloaryl triazole compounds as insecticides and acaricides. 1. Phenyl thiophen-2-yl triazoles

Article abstract of DOI:10.1021/jf071498s

An extended lipophilic system that incorporated some key elements of first-generation 2,6-dihaloaryl actives, such as 1, demonstrated desirable efficacy against chewing insects as well as sap-feeding insects. These four-ring systems, based on 2, were acce

Full text of DOI:10.1021/jf071498s

J. Agric. Food Chem. 2007, 55, 7517−7526 7517
Structure−Activity Relationship Development of Dihaloaryl
Triazole Compounds as Insecticides and Acaricides. 1. Phenyl
Thiophen-2-yl Triazoles
DENISE P. CUDWORTH,*,† VIDYADHAR B. HEGDE,*,† MAURICE C. H. YAP,†
KATHERINE A. GUENTHENSPBERGER,† CHRISTOPHER T. HAMILTON,§
JAMES T. PECHACEK,† PETER L. JOHNSON,† SCOTT J. BIS,§ F. EUGENE TISDELL,†
JAMES E. DRIPPS,† TIMOTHY J. BRUCE,† LEONARD P. DINTENFASS,†
JAMES M. GIFFORD,† LAURA L. KARR,† MARGARET K. KEMPE,†
D’LEE C. MCCORMICK,† AND JOSEPH R. SCHOONOVER, JR.†
Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, Indiana 46268, and The Dow Chemical
Company, Midland, Michigan 48674
An extended lipophilic system that incorporated some key elements of first-generation 2,6-dihaloaryl
actives, such as 1, demonstrated desirable efficacy against chewing insects as well as sap-feeding
insects. These four-ring systems, based on 2, were accessed primarily via Suzuki couplings of
halothiophene derivatives with appropriately substituted boronic acids. In particular, phenylthiophene
systems that incorporated haloxyether groups, such as those in 3, 4, and 5, had the broadest spectrum
of activity across chewing and sap-feeding insect pests. Expansion of this structure-activity
relationship to include compounds with differing substitution patterns on the thiophene-C-ring and
aryl-D-rings was undertaken. The synthesis and insecticidal activity of 3-aryl-5-(thiophen-2-yl)-1-methyl-
1H-[1,2,4]triazoles will be described.
KEYWORDS: Insecticides; 2,6-dihaloaryl triazoles; C-ring thiophenes; 2-substitution
INTRODUCTION
In recent years, there have been a number of patent applica-
tions related to 2,6-dihaloarylheterocycles (1-9). The key
feature of these molecules is a 2,6-dihalogenated aryl A-ring
attached to a central nitrogen-containing B-ring heterocycle
(Figure 1). Early work at Dow AgroSciences (DAS) was
initiated because of the interesting growth regulatory activity
exhibited by an Ihara/Kumiai material, 6 (7, 8). The unknown
mode of action (MOA) and clean toxicity profile made this class
of compounds worthy of pursual for potential leads. Progress
toward this goal resulted in the discovery of 7, a highly
efficacious compound with activity against aphids (10), contain-
ing a C-ring thiophene rather than a C-ring pyridine. Subsequent
work provided a number of proprietary leads (11, 12), the best
of which was 1 (13-15). Compound 1 has aphid and mite
control comparable to that of 7 with commercial levels of
whitefly control.
Work since then has focused on developing a lead that has a
spectrum complementary to that of compound 1. To find a
* Authors to whom correspondence should be addressed [(D.P.C.)
telephone (317) 337-3134, fax (317) 337-3215, e-mail dpcudworth@
dow.com; (V.B.H.) telephone (317) 337-3032, fax (317) 337-3215, e-mail
vbhegde@dow.com].
† Dow AgroSciences LLC.
§ The Dow Chemical Co.
Figure 1. Series of 2,6-dihaloaryl heterocycles.
10.1021/jf071498s CCC: $37.00
© 2007 American Chemical Society
Published on Web 08/14/2007

7518 J. Agric. Food Chem., Vol. 55, No. 18, 2007
Cudworth et al.
added via syringe to a solution of 3-chlorothiophene-2-carboxylic acid
(2-chloro-6-fluorophenyl)methylsulfanylmethyleneamide (9.36 g, 27.5
mmol) in toluene (250 mL). The reaction mixture was stirred at 25 °C
for 60 h. The reaction mixture was concentrated under reduced pressure,
and then CH2Cl2 was added until most of the material was dissolved.
The remaining solid was collected via suction filtration. The filtrate
was concentrated and triturated with an ether/hexanes mixture to give
second-generation 2,6-dihalo active, compounds exhibiting
lepidopteran-aphid (chewing and sap-feeding insect pests,
respectively) coactivity were sought. In the structure-activity
relationship (SAR) development around 1, compounds with
extended lipophilicity (16), such as alkyne 2, were synthesized,
and it was discovered that these compounds retained sap-feeding
insect pest activity while also exhibiting lepidopteran activity.
Thus, it was determined that the extended lipophilicity provided
the lepidopteran activity in the thiophene series. Removal of
the photolytically unstable alkynyl moiety and direct attachment
of the phenyl D-ring to the thiophene C-ring at either the 4- or
5-position of the thiophene resulted in compounds that retained
both chewing and sap-feeding insect pest activity. SAR devel-
opment demonstrated that ring systems with similar lipophilicity,
such as 3, an early testing candidate, 4, and a field testing
candidate, 5, had broad-spectrum chewing and sap-feeding insect
pest activity (17).
1
a burnt orange-brown solid (5.23 g, 57% yield): mp 82-87 °C; H
NMR (CDCl3), δ 7.56 (d, J ) 5.4 Hz, 1H), 7.47-7.29 (m, 2H), 7.13-
7.05 (m, 2H), 4.03 (s, 3H); EIMS, m/z 327 ([M - H]+). Anal. Calcd
for C13H8Cl2FN3S: C, 47.58; H, 2.46; N, 12.80; S, 9.77. Found: C,
47.29; H, 2.38; N, 12.63; S, 9.95.
The following compounds were prepared according to the procedure
below:
5-(5-Bromo-3-chlorothiophen-2-yl)-3-(2-chloro-6-fluorophenyl)-
1-methyl-1H-[1,2,4]triazole (10a). 3-(2-Chloro-6-fluorophenyl)-5-(3-
chlorothiophen-2-yl)-1-methyl-1H-[1,2,4]triazole (9, Y, R1 ) Cl; 5.75
g, 17.5 mmol) was taken up in glacial HOAc (70 mL). To this were
added NaOAc (5.40 g, 65.8 mmol) and bromine (1.4 mL, 27.1 mmol).
The reaction mixture was stirred at 75 °C for 16 h. TLC (30% EtOAc/
hexanes) showed incomplete reaction. Thus, more NaOAc (10.7 g, 130
mmol) and bromine (2.8 mL, 54.3 mmol) were added. The mixture
was stirred at 75 °C for 21 h and then was cooled to 25 °C. The reaction
mixture was quenched with cold (0 °C) saturated aqueous NaHCO3
(500 mL). The aqueous layer was extracted with Et2O (3 × 150 mL).
The combined organic extracts were washed with H2O (200 mL) and
saturated aqueous NaCl (200 mL), dried (MgSO4), filtered, and
concentrated. The quench and extraction procedures were repeated due
to the presence of acetic acid. The extractions were done until the
organic layer was pH >7. Column chromatography (20-30% Et2O/
hexanes) gave three compounds, the second of which was the desired
Expansion of this area to include compounds with various
substitutions on the C-ring thiophene, as well as on the D-ring
(alkyl, alkenyl, aryl), was undertaken. The synthesis and
insecticidal activity of these phenylthiophenes will be described.
MATERIALS AND METHODS
Synthesis. All nonaqueous reactions were carried out under a
nitrogen atmosphere. Reaction solvents were purchased from Aldrich
(Sure/Seal) and used as is. Unless otherwise noted, all reagents and
solvents were used as received. Melting points were recorded on a
Thomas Hoover Melting Point apparatus using the appropriate partial
immersion thermometer. Elemental analyses were conducted by
Midwest Microlab, Indianapolis, IN. Reactions were monitored by thin-
layer chromatography (TLC) on 250 µm precoated Analtech Uniplate
plates, with visualization by ultraviolet light. Flash or gravity column
chromatography was performed on 230-400 mesh silica gel 60 from
EM Science, Darmstadt, Germany, using ACS grade solvents. Reversed-
phase high-performance liquid chromatography (RP-HPLC) was con-
ducted on a Gilson Liquid Handler 215 with HPLC grade acetonitrile
and water (both with 0.1% acetic acid). Mass spectral data were obtained
by electron ionization on a Hewlett-Packard Series 1100 mass selective
detector, a Hewlett-Packard 5890 series II with a Hewlett-Packard
5890A mass spectrometer, or a Hewlett-Packard 6890 series GC system
with a 5973 mass selective detector. High-resolution mass spectral
(HRMS) data were acquired on a Thermo Finnigan LTQ-FT mass
spectrometer (S/N 06120F). NMR spectra were obtained in CDCl3 and
DMSO-d6, used as purchased, and were recorded on a Varian Gemini
(300 MHz) spectrometer (unless otherwise stated), referenced to an
internal standard of tetramethylsilane (TMS 1H: δ 0.00). 1H-1H
couplings are assumed to be first order, and peak multiplicity is reported
as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), or b
(broad).
3-(2-Chloro-6-fluorophenyl)-5-(3-chlorothiophen-2-yl)-1-methyl-
1H-[1,2,4]triazole (9a). To a suspension of 3-chlorothiophene-2-
carboxylic acid (8, R1 ) Cl; 5.02 g, 30.8 mmol) in 1,2-dichloroethane
(DCE, 250 mL) were added thionyl chloride (2.5 mL, 34.1 mmol) and
N,N-dimethylformamide (DMF, 5 drops from a Pasteur pipet). After
refluxing under N2 for 5 h, the reaction mixture was cooled to 25 °C
and concentrated under reduced pressure. The residue was dissolved
in DCE (250 mL) and added to 2-chloro-6-fluorothiobenzimidic acid
methyl ester hydrogen bromide (8.80 g, 30.9 mmol) at 25 °C. To the
suspension was added dry pyridine (5.5 mL, 68 mmol). The reaction
mixture was stirred for 16 h and then was washed with H2O (250 mL),
saturated aqueous NaHCO3 (250 mL), and saturated aqueous NaCl
(250 mL). The organic layer was dried (Na2SO4), filtered, and
concentrated under reduced pressure to give an orange-brown solid (9.36
g, 87% yield): mp 118-121 °C; 1H NMR (CDCl3), δ 7.50 (d, J ) 5.1
Hz, 1H), 7.34-7.28 (m, 1H), 7.18 (d, J ) 8.0 Hz, 1H), 7.04-6.98 (m,
2H), 2.65 (s, 3H); EIMS, m/z 312 ([M - Cl]+). Anal. Calcd for C13H8-
Cl2FNOS2: C, 44.84; H, 2.32; N, 4.02; S, 18.41. Found: C, 44.83; H,
2.34; N, 3.92; S, 18.39. Methylhydrazine (6.0 mL, 112 mmol) was
1
product, an off-white solid (3.67 g, 51% yield): mp 125-128 °C; H
NMR (CDCl3), δ 7.39-7.30 (m, 2H), 7.15-7.09 (m, 2H), 4.05 (s, 3H);
EIMS, m/z 407 ([M + H]+). Anal. Calcd for C13H7BrCl2FN3S: C,
38.36; H, 1.73; N, 10.32; S, 7.88. Found: C, 38.13; H, 1.83; N, 10.36;
S, 8.07.
5-(5-Bromo-3-chlorothiophen-2-yl)-3-(2,6-difluorophenyl)-1-methyl-
1H-[1,2,4]triazole (10b). The product was isolated as a white solid
1
(51% yield): mp 134-137 °C; H NMR (CDCl3), δ 7.43-7.33 (m,
1H), 7.08 (s, 1H), 7.06-6.98 (m, 2H), 4.02 (s, 3H); EIMS, m/z 391
([M + H]+). Anal. Calcd for C13H7BrClF2N3S: C, 39.97; H, 1.81; N,
10.76; S, 8.21. Found: C, 39.74; H, 1.82; N, 10.54; S, 8.27.
The following is an example of lithium-halogen exchange, followed
by treatment with an electrophile (iodomethane):
5-(4-Bromo-3,5-dimethylthiophen-2-yl)-3-(2-chloro-6-fluorophe-
nyl)-1-methyl-1H-[1,2,4]triazole (11a). n-Butyllithium (0.7 g, 10.8
mmol) was added dropwise to a solution of 3-(2-chloro-6-fluorophenyl)-
5-(4,5-dibromo-3-methylthiophen-2-yl)-1-methyl-1H-[1,2,4]triazole (11,
Y ) Cl, R4 ) Br; 5 g, 10.8 mmol) in THF (70 mL) at -70 °C and
stirred for 1 h. Iodomethane (1.6 g, 11.29 mmol) was added to the
reaction mixture, and the reaction mixture was allowed to warm to
25 °C. After the addition of saturated aqueous NH4Cl (10 mL), the
organic layer was separated, washed with H2O and saturated aqueous
NaCl (20 mL), dried (Na2SO4), filtered, and concentrated. Column
chromatography (10% EtOAc/hexanes) afforded the product as a yellow
oil (2.0 g, 47% yield): 1H NMR (CDCl3), δ 7.38-7.28 (m, 2H), 7.13-
7.07 (m, 1H), 3.99 (s, 3H), 2.48 (s, 3H), 2.32 (s, 3H); EIMS, m/z 400
([M]+). Anal. Calcd for C15H12ClBrFN3S: C, 44.96; H, 3.02; N, 10.49.
Found: C, 44.94; H, 3.01; N, 10.29.
General Procedure for the Preparation of 3, 4, 12, and 13. Pd-
(PPh3)2Cl2 (10 mol %) was added to a suspension of the 1,2,4-triazole
(0.49 mmol), the boronic acid (1.01 equiv), Na2CO3 (1.5 equiv), and
(o-tolyl)3P (0.10 equiv) in CH3CN/H2O (10:1, 4 mL). The mixture was
stirred at reflux under N2 for 20 h and at 25 °C for 24 h. The reaction
mixture was quenched with 1 N HCl (50 mL) and extracted with Et2O
(3 × 50 mL). The combined organic extracts were washed with
saturated aqueous NaCl (50 mL), dried (MgSO4), filtered, and
concentrated. Column chromatography, eluting with acetone/, ether/,
or ethyl acetate/hexane mixtures, provided the product. Preparative
information and mass spectral and proton NMR, as well as microana-

Dihalophenyl Triazoles as Insecticides and Acaricides
J. Agric. Food Chem., Vol. 55, No. 18, 2007 7519
Table 1. Preparative Information and Mass Spectral and Proton NMR Data for Compounds 3, 4, 12a−o, and 13a−
ha
yield
(%)
compd
Y
R1
R2
R3
R4
mp (
108
96
°
C)
109
97
MSb (m/z)
1H NMR data (CDCl3)
7.11 (m, 7H), 6.96 (m, 1H), 3.92 (s, 3H), 2.16 (s, 3H)
7.62 (d, 2H), 7.38 7.21 (m, 5H), 7.07 (m, 1H), 4.05 (s, 3H), 2.41 (s, 3H)
2.1, 2.9, 8.7 Hz, 2H), 7.40 7.26 (m, 5H), 7.15 7.08 (m, 1H),
+
3
4
12a
Cl
Cl
Cl
CH3
CH3
Cl
4-OCF3
4-OCF3
4-OCF3
H
H
H
H
H
H
69
72
62
−
467 ([M] )
7.29−
+
−
467 ([M] )
−
+
120−
123
487 ([M] )
7.62 (ddd, J
4.08 (s, 3H)
)
−
−
+
12b
12c
12d
Cl
Cl
Cl
Cl
Cl
Cl
4-CF3
4-CH3
4-OEt
H
H
H
H
H
H
60
69
66
133
111
126
−
−
−
136
115
128
471 ([M] )
7.70 (s, 4H), 7.38
7.49 (d, J 8.0 Hz, 2H), 7.46
7.50 (dd, J 8.7, 2.0 Hz, 2H), 7.39
6.96 6.92 (m, 1H), 4.11 (m, 5H), 1.44 (t, J
7.57 (d, J 8.4 Hz, 2H), 7.46 (d, J 8.4 Hz, 2H), 7.37
7.26 (s, 1H and CDCl3), 7.14 7.08 (m, 1H), 4.08 (s, 3H)
7.23 (m, 5H), 7.14 7.08 (m, 1H), 4.08 (s, 3H),
−
7.30 (m, 3H), 7.15
7.23 (m, 5H), 7.14
7.29 (m, 2H), 7.15 (s, 1H), 7.14
7.1 Hz, 3H)
7.29 (m, 2H),
−
7.09 (m, 1H), 4.09 (s, 3H)
7.08 (m, 1H), 4.09 (s, 3H)
7.08 (m, 1H),
+
417 ([M] )
)
)
−
−
+
419 ([M
−
Et] )
−
−
−
)
+
12e
12f
Cl
Cl
Cl
Cl
4-Br
H
H
H
H
44
66
126
−
128
126
483 ([M] )
)
)
−
−
+
4-SCH3
125−
449 ([M] )
7.50 (d, J
2.52 (s, 3H)
7.72 (q, J
)
8.7 Hz, 2H), 7.40
−
−
+
12g
12h
12i
Cl
Cl
Cl
CH3
CH3
CH3
4-CF3
3-Cl
3-OEt
H
4-F
H
H
H
H
70
58
73
85
121
−
−
86
122
87
451 ([M] )
)
8.3 Hz, 4H), 7.41
−
7.25 (m, 3H), 7.10 (m, 1H), 4.12 (s, 3H), 2.43 (s, 3H)
−6.95 (m, 5H), 3.95 (s, 3H), 2.25 (s, 3H)
+
436 ([M] )
7.55 (d, 2H), 7.31 (m, 1H), 7.22
7.20 7.18 (m, 2H), 7.15 7.07 (m, 2H), 6.89
2.42 (s, 3H), 1.44 (t, J 6.96 Hz, 3H)
7.40 7.34 (m, 2H), 7.33 7.28 (m, 2H), 7.13
4.12
7.51 7.47 (m, 2H), 7.39
2.32 (s, 3H), 2.24 (s, 3H)
+
84−
428 ([M] )
−
−
−
6.85 (m, 1H), 4.12
−
4.05 (m, 5H),
)
+
12j
Cl
Cl
F
CH3
CH3
Cl
4-OEt
H
H
H
H
H
CH3
CH3
H
31
47
65
69
64
147
109
105
139
120
−
−
−
−
−
148
441 ([M] )
−
−
−
6.99 (m, 1H), 6.95
−6.78 (m, 2H),
−4.05 (m, 5H), 2.31 (s, 3H), 2.20 (s, 3H), 1.45 (t, J
)
7.0 Hz, 3H)
+
12k
12l
4-OCF3
4-OCF3
4-CH3
4-OEt
112
107
141
123
481 ([M] )
−
−7.28 (m, 4H), 7.14
−
7.08 (m, 1H), 4.05 (s, 3H),
+
471 ([M] )
7.63−7.59 (m, 2H), 7.41−7.36 (m, 1H), 7.30−7.25 (m, 3H), 7.06−7.00 (m, 2H),
4.07 (s, 3H)
+
12m
12n
F
Cl
H
401 ([M] )
7.47 (m, 2H), 7.41−7.35 (m, 1H), 7.26−7.22 (m, 3H), 7.05−7.02 (m, 2H),
4.07 (s, 3H), 2.39 (s, 3H)
7.50 (d, J 8.7 Hz, 2H), 7.38 (m, 1H), 7.15 (s, 1H), 7.05
6.94 (d, J 8.7 Hz, 2H), 4.06 (m, 5H), 1.44 (t, J 6.9 Hz, 3H)
7.70 (s, 4H), 7.42 7.35 (m, 2H), 7.03 (t, J 8.05 Hz, 2H), 4.08 (s, 3H)
7.39 7.30 (m, 5H), 7.13 6.98 (m, 1H), 6.96 (d, J 8.4 Hz, 2H), 4.06 (s, 3H),
2.31 (s, 3H), 1.45 (t, J 7.0 Hz, 3H)
7.71 (d, J 8.0 Hz, 2H), 7.53 (d, J 8.0 Hz, 2H), 7.49 (s, 1H), 7.38
7.10 (dd, J 7.3 Hz, 1H), 4.08 (s, 3H), 2.34 (s, 3H)
7.38 7.28 (m, 7H), 7.14 7.08 (m, 1H), 4.06 (s, 3H), 2.96 (m, 1H), 2.33 (s, 3H)
1.30 (d, J 6.6 Hz, 6H)
7.38 7.28 (m, 2H), 7.13 7.07 (m, 2H), 4.00 (s, 3H), 2.27 (s, 3H), 2.22 (s, 3H)
7.70 (d, J 8.1 Hz, 2H), 7.38 7.24 (m, 6H), 7.13 7.07 (m, 1H), 4.06 (s, 3H),
2.36 (s, 3H), 2.14 (s, 3H)
7.38 7.24 (m, 6H), 7.13 7.07 (m, 1H), 4.06 (s, 3H), 2.36 (s, 3H), 2.14 (s, 3H)
7.43 (d, J 8.4 Hz, 2H), 7.41 7.28 (m, 2H), 7.17 (d, J 8.0 Hz, 2H),
7.13 7.06 (m, 1H), 4.05 (s, 3H), 2.35 (s, 3H), 2.13 (s, 3H)
7.37 7.28 (m, 4H) 7.18 7.13 (m, 2H), 7.13 7.06 (m, 1H), 4.05 (s, 3H),
3.01 2.92 (m, 1H), 2.36 (s, 3H), 2.15 (s, 3H), 2.13 (d, J 7.0 Hz, 7H)
+
F
Cl
H
432 ([M
+
H] )
)
−6.99 (m, 2H),
)
)
+
12o
13a
F
Cl
Cl
CH3
4-CF3
4-OEt
H
H
H
H
63
80
156−
162
127
455 ([M] )
−
)
+
124−
427 ([M
+
H] )
−
−
)
)
+
13b
13c
Cl
Cl
CH3
CH3
4-CF3
4-i-Pr
H
H
H
H
66
53
102
−
−
−
103
111
143
467 ([M] )
)
)
−7.31 (m, 2H),
)
+
109
425 ([M
+
H] )
−
−
)
+
13d
13e
Cl
Cl
CH3
CH3
4-OEt
4-CF3
H
H
CH3
CH3
35
27
140
oil
322 ([M] )
−
−
+
466 ([M] )
)
−
−
+
13f
13g
Cl
Cl
CH3
CH3
4-OCF3
4-i-Pr
H
H
CH3
CH3
26
19
93−95
482 ([M] )
−
−
+
154−
155
432 ([M] )
)
−
)
−
+
13h
Cl
CH3
4-Cl
H
CH3
25
85−89
440 ([M] )
−
−
−
−
)
a See Figure 4 for structures. b Electron-impact ionization.
lytical and HRMS, data for compounds 3, 4, 12a-o, and 13a-h can
be found in Tables 1 and 2, respectively.
J ) 7.1 Hz, 3H); EIMS, m/z 347 ([M]+). Ethyl 4,5-dibromo-3-
chlorothiophene-2-carboxylate (5.52 g, 15.8 mmol) and lithium hy-
droxide (0.716 g, 31.7 mmol) were taken up in mixture of THF (30
mL) and water (30 mL). The reaction mixture was stirred at 25 °C for
32 h. The aqueous layer was made acidic by the dropwise addition of
concentrated HCl and extracted with Et2O (3 × 50 mL). The combined
organic extracts were dried (Na2SO4), filtered, and concentrated to give
the product as a white solid (4.38 g, 86% yield) that was used without
purification: 1H NMR (CDCl3 and DMSO-d6), δ 4.15 (bs, 1H); MS,
m/z 320 ([M]+).
3-(2-Chloro-6-fluorophenyl)-5-(4,5-dibromo-3-chlorothiophen-2-
yl)-1-methyl-1H-[1,2,4]triazole (15). 4,5-Dibromo-3-chlorothiophene-
2-carboxylic acid (14, 2.05 g, 6.42 mmol) was taken up in DCE (60
mL) to which were added thionyl chloride (0.49 mL, 6.71 mmol) and
catalytic DMF (5 drops). The mixture was stirred at reflux under N2
for 6 h. More thionyl chloride (0.49 mL) was added, and the mixture
was stirred at 25 °C for 16 h. The mixture was concentrated to a tan
solid that was dissolved in DCE (60 mL), to which were added 2-chloro-
6-fluoro-thiobenzimidic acid methyl ester methyl sulfate (2.02 g, 6.42
mmol) and pyridine (1.2 mL, 14.8 mmol). The reaction mixture was
stirred at 25 °C for 48 h. The organic layer was washed with H2O
(75 mL), 1 N HCl (75 mL), saturated aqueous NaHCO3 (75 mL), and
saturated aqueous NaCl (75 mL), dried (MgSO4), filtered, and
concentrated to give the product (2.40 g, 73% yield) as a burnt orange
solid: mp 111-118 °C; 1H NMR (CDCl3), δ 7.32 (ddd, J ) 5.8, 8.0,
4,5-Dibromo-3-chlorothiophene-2-carboxylic Acid (14). Catalytic
DMF (5 drops) was added to a mixture of 3-chlorothiophene-2-
carboxylic acid (8, R1 ) Cl; 5.0 g, 30.8 mmol) and thionyl chloride
(2.4 mL, 32.9 mmol) in DCE (250 mL). The reaction mixture was
stirred at reflux under N2 for 4.5 h and then was cooled to 25 °C.
Absolute EtOH (25 mL, 430 mmol) was added, and the reaction mixture
was stirred at 25 °C for 16 h. The mixture was washed with saturated
aqueous NaHCO3 (200 mL), H2O (200 mL), and saturated aqueous
NaCl (200 mL), dried (MgSO4), filtered, and concentrated. Column
chromatography (5% Et2O/hexanes) provided the product (3.99 g, 68%
yield) as a light yellow oil: 1H NMR (CDCl3), δ 7.46 (d, J ) 5.1 Hz,
1H), 7.01 (d, J ) 5.1 Hz, 1H), 4.36 (q, J ) 7.2 Hz, 2H), 1.38 (t, J )
7.1 Hz, 3H); EIMS, m/z 190 ([M]+). Ethyl 3-chlorothiophene-2-
carboxylate (3.96 g, 20.7 mmol) in a suspension of NaOAc (12.7 g,
154 mmol) and glacial HOAc (35 mL) was treated with bromine (9.6
mL, 186 mmol). The reaction mixture was stirred at 75 °C under N2
for 136 h and then at 25 °C for 144 h. The reaction mixture was poured
onto ice-cold saturated aqueous NaHCO3 and aqueous NaHSO3. The
mixture was stirred with Et2O (100 mL) for 30 min. Extraction with
Et2O (3 × 150 mL) gave an organic layer that was washed with H2O
(150 mL) and saturated aqueous NaCl (150 mL), dried (MgSO4), and
concentrated to give the product as a white solid (5.83 g, 80% yield):
mp 58-63 °C; 1H NMR (CDCl3), δ 4.37 (q, J ) 7.1 Hz, 2H), 1.38 (t,

7520 J. Agric. Food Chem., Vol. 55, No. 18, 2007
Cudworth et al.
HRMS (theory)
Table 2. Microanalytical and High-Resolution Mass Spectral (HRMS) Data for Compounds in Table 1
compd
molecular formula
% C (theory)
% H (theory)
% N (theory)
% S (theory)
3
4
C
C
C
C
C
C
C
C
C
C
C
C
C
21H14ClF4N3OS
21H14ClF4N3OS
20H11Cl2F4N3OS
20H11Cl2F4N3S
20H14Cl2FN3S
21H16Cl2FN3OS
19H11BrCl2FN3S
20H14Cl2FN3S2
21H14ClF4N3S
20H13Cl2F2N3S
22H19ClFN3OS
23H21ClFN3OS
22H16ClF4N3OS
467.0475 (467.0482)
467.0476 (467.0482)
12a
12b
12c
12d
12e
12f
12g
12h
12i
49.42 (49.20)
51.01 (50.86)
57.19 (57.43)
56.33 (56.26)
47.32 (47.23)
53.17 (53.34)
2.38 (2.27)
2.36 (2.35)
3.46 (3.37)
3.62 (3.60)
2.34 (2.29)
3.19 (3.13)
8.37 (8.61)
8.67 (8.90)
9.64 (10.04)
9.31 (9.37)
8.46 (8.70)
9.19 (9.33)
6.61 (6.57)
6.48 (6.79)
7.16 (7.66)
7.13 (7.15)
6.68 (6.64)
14.28 (14.24)
451.0531 (451.0533)
435.0173 (435.0175)
427.0920 (427.9021)
12j
12k
12l
62.36 (62.51)
54.68 (54.83)
50.90 (50.91)
59.83 (59.78)
58.44 (58.40)
52.81 (52.70)
61.74 (61.75)
4.67 (4.79)
3.39 (3.35)
2.44 (2.35)
3.61 (3.51)
3.88 (3.73)
2.50 (2.43)
4.53 (4.48)
9.45 (9.51)
8.65 (8.72)
8.64 (8.91)
10.22 (10.46)
9.48 (9.73)
9.13 (9.22)
9.63 (9.82)
C20H11ClF5N3OS
6.93 (6.80)
8.16 (7.98)
7.23 (7.42)
7.11 (7.03)
12m
12n
12o
13a
13b
13c
13d
13e
13f
13g
13h
C
C
C
C
C
C
C
C
C
C
C
20H14ClF2N3S
21H16ClF2N3OS
20H11ClF5N3S
22H19ClFN3OS
21H14ClF4N3S
23H23ClFN3S
23H21ClFN3OS
22H16ClF4N3S
22H16ClF4N3OS
24H23ClFN3S
21H16Cl2FN3S
451.0531 (451.0533)
64.51 (64.86)
5.02 (4.97)
9.78 (9.86)
441.1074 (441.1078)
465.0687 (465.0690)
481.0641 (481.0639)
439.1281 (439.1284)
431.0427 (431.0426)
8.4 Hz, 1H), 7.19 (d, J ) 8.0 Hz, 1H), 7.03 (ddd, J ) 0.85, 8.0, 8.4
Hz, 1H), 2.65 (s, 3H); EIMS, m/z 470 ([M - Cl]+). 4,5-Dibromo-3-
chlorothiophene-2-carboxylic acid (2-chloro-6-fluorophenyl)methyl-
sulfanyl methyleneamide (2.14 g, 4.22 mmol) was dissolved in toluene
(42 mL) under N2. To this solution was added methylhydrazine (0.90
mL, 16.9 mmol), and the mixture was stirred at 25 °C for 40 h. The
mixture was concentrated and triturated with hexanes to give the crude
product. The crude product was dissolved in a minimum of CH2Cl2,
and a few drops of hexanes were added. The solution was allowed to
crystallize over 48 h, providing the product as a tan solid (499 mg,
General Procedure for the Preparation of 5, 18, and 19. The
triazole (12 or 13, 1.20 mmol) was dissolved in CH2Cl2 (12 mL) under
N2 and was cooled to 0 °C. To this was added BBr3 (1.0 M solution in
CH2Cl2; 2.0 mL, 2.0 mmol) dropwise via syringe. The cooling bath
was removed immediately, and the reaction mixture was allowed to
warm to 25 °C and stirred for 20 h. The mixture was poured onto H2O
(100 mL) and stirred at 25 °C for 30 min. The layers were partitioned,
and the aqueous layer was extracted with CH2Cl2 (2 × 50 mL). The
combined organic extracts were washed with H2O (50 mL) and saturated
aqueous NaCl (50 mL), dried (Na2SO4), filtered, and concentrated.
Column chromatography gave the corresponding phenol. The phenol
(0.438 mmol) was taken up in DMF (1.6 mL) to which was added
25% NaOH (a few drops). The mixture became a bright yellow color
and was stirred at 25 °C for 10 min. Bromotrifluoroethylene, chlorot-
rifluoroethylene, or hexafluoropropene (g, excess) was then bubbled
through the mixture for 10-15 min. TLC showed little reaction, so
more 25% NaOH (a few drops) was added, followed by the bubbling
of more gas for 10 min. TLC (30% Et2O/hexanes) at this time showed
no starting material, only a less polar spot. The mixture was stirred at
25 °C for 1 h. The mixture was poured onto H2O (50 mL) and was
extracted with Et2O (3 × 50 mL). The combined organic extracts were
washed with H2O (50 mL) and saturated aqueous NaCl (50 mL), dried
(Na2SO4), filtered, and concentrated to a tan solid. Column chroma-
tography, eluting with an acetone/, ether/, or ethyl acetate/hexane
mixture, gave the product. Preparative information and mass spectral
and proton NMR, as well as microanalytical and HRMS, data for
compounds 5, 18a-h, and 19a-h can be found in Tables 3 and 4,
respectively.
1
24% yield): mp 180-182 °C; H NMR (CDCl3), δ 7.40-7.27 (m,
2H), 7.14-7.08 (m, 1H), 4.03 (s, 3H); EIMS, m/z 485 ([M]+).
The following compounds were prepared according to the procedure
below:
5-[4-Bromo-3-chloro-5-(4-trifluoromethoxyphenyl)thiophen-2-yl]-
3-(2-chloro-6-fluorophenyl)-1-methyl-1H-[1,2,4]triazole (16a). 3-(2-
Chloro-6-fluorophenyl)-5-(4,5-dibromo-3-chlorothiophen-2-yl)-1-methyl-
1H-[1,2,4]triazole (15, 203 mg, 0.418 mmol), 4-trifluoromethoxyphenyl
boronic acid (87.2 mg, 0.423 mmol), and K2CO3 (85.8 mg, 0.620 mmol)
were taken up in PhCH3 (4 mL). The mixture was degassed with N2
for 15 min, and then Pd(PPh3)4 (cat.) was added. The reaction mixture
was stirred at 90-95 °C under N2 for 7.5 h. TLC (20% Et2O/hexanes)
showed the presence of 15. More Pd(PPh3)4 was added, and the mixture
was stirred at 90-95 °C for 16 h. Reaction was still incomplete. The
reaction mixture was quenched with 1 N HCl (50 mL) and was extracted
with Et2O (3 × 50 mL). The combined organic extracts were washed
with saturated aqueous NaCl (50 mL), dried (Na2SO4), filtered, and
concentrated. Column chromatography (20% Et2O/hexanes) provided
the product as a white solid (44 mg, 18% yield): mp 170-172 °C; 1H
NMR (CDCl3), δ 7.69 (d, J ) 8.7 Hz, 2H), 7.38-7.29 (m, 4H), 7.23-
7.09 (m, 1H), 4.09 (s, 3H); EIMS, m/z 567 ([M]+).
5-[4-Bromo-3-chloro-5-(4-trifluoromethylphenyl)thiophen-2-yl]-
3-(2-chloro-6-fluorophenyl)-1-methyl-1H-[1,2,4]triazole (16b). The
product was isolated as a white solid (28% yield): mp 167-170 °C;
1H NMR (CDCl3), δ 7.50 (dd, J ) 8.7, 2.0 Hz, 2H), 7.39-7.29 (m,
2H), 7.15 (s, 1H), 7.14-7.08 (m, 1H), 6.96-6.92 (m, 1H), 4.11 (m,
5H), 1.44 (t, J ) 7.1 Hz, 3H); EIMS, m/z 551 ([M]+).
5-[4-Bromo-3-chloro-5-(4-ethoxyphenyl)thiophen-2-yl]-3-(2-chloro-
6-fluorophenyl)-1-methyl-1H-[1,2,4]triazole (16c). The product was
isolated as a white solid (41% yield): mp 145-150 °C; 1H NMR
(CDCl3), δ 7.58 (d, J ) 8.7 Hz, 2H), 7.40-7.30 (m, 2H), 7.14-7.08
(m, 1H), 6.99 (d, J ) 8.7 Hz, 2H), 4.13-4.03 (m, 5H), 1.45 (t, J ) 6.9
Hz, 3H); EIMS, m/z 527 ([M]+).
5-{5-Bromo-4-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-3-meth-
ylthiophen-2-yl}-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-[1,2,4]-
triazole (20). Bromine (0.03 g, 0.2 mmol) in HOAc (0.5 mL) was added
dropwise to a solution of 5-{4-[4-(2-bromo-1,1,2-trifluoroethoxy)-
phenyl]-3-methylthien-2-yl}-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-
[1,2,4]triazole (19, X ) Br, Y ) Cl, R1 ) CH3, R4 ) H; 0.1 g, 0.2
mmol) in HOAc (1 mL) at 0 °C. The reaction was allowed to warm to
25 °C and stirred for 50 h. The reaction mixture was made basic with
saturated aqueous NaHCO3 (30 mL) and was extracted with Et2O (3
× 30 mL). The combined extracts were washed with saturated aqueous
NaCl, dried (Na2SO4), filtered, and concentrated. Column chromatog-
raphy (20% Et2O/hexanes) gave the product (88 mg, 77% yield) as a
clear oil: 1H NMR (CDCl3), δ 7.40-7.29 (m, 6H), 7.14-7.08 (m, 1H),
6.58 (dt, J ) 47.6, 5.1, 4.0, 4.4 Hz, 1H), 4.06 (s, 3H), 2.19 (s, 3H);
EIMS, m/z 636 ([M + H]+).

Dihalophenyl Triazoles as Insecticides and Acaricides
J. Agric. Food Chem., Vol. 55, No. 18, 2007 7521
h, and 19a
ga
Table 3. Preparative Information and Mass Spectral and Proton NMR Data for Compounds 5, 18a
−
−
yield
(%)
compd
Y
R1
R2
R3
H
R4
mp (
°
C)
MSb (m/z)
1H NMR data (CDCl3)
7.11 (m, 5H), 7.02 (t, 1H), 6.30 and 6.13 (t, 1H),
3.99 (s, 3H), 2.34 (s, 3H)
7.60 (m, 2H), 7.40 7.25 (m, 5H), 7.14
JH,F(gem) 47.6 Hz, JH,F(vic) 4.67 Hz, 1H), 4.08 (s, 3H)
H] ) 7.55 (d, 2H), 7.31 7.21 (m, 3H), 7.15 (s, 1H), 7.02 (t, 1H), 5.85 (t, 1H),
3.99 (s, 3H), 2.34 (s, 3H)
H] ) 7.48 (d, 2H), 7.22 7.15 (m, 3H), 7.11 (s, 1H), 6.99 (t, 1H),
4.95 4.79 (m, 1H), 3.93 (s, 3H), 2.27 (s, 3H)
7.60 (m, 2H), 7.40 7.28 (m, 5H), 7.14 7.08 (m, 1H), 6.29 (dt,
JH,F(gem) 47.9 Hz, JH,F(vic) 3.93 Hz, 1H), 4.08 (s, 3H)
H] ) 7.53 7.50 (m, 1H) 7.46 7.44 (m, 1H), 7.41 (d, J 0.73 Hz, 1H),
7.38 (s, 1H), 7.37 7.29 (m, 2H), 7.21 7.18 (m, 1H),
7.13 7.07 (m, 1H), 6.57 (dt, J 47.6, 4.76 Hz, 1H),
4.08 (s, 3H), 2.43 (s, 3H)
7.54 7.51 (m, 1H), 7.42 (s, 1H), 7.45 (s, 1H), 7.40 (s, 1H), 7.38
7.25 (s, 1H), 7.21 7.18 (m, 1H), 7.14 7.08 (m, 1H),
6.30 (dt, J 48.3, 4.0 Hz, 1H), 4.08 (s, 3H), 2.43 (s, 3H)
7.46 (m, 2H) 7.39 7.29 (m, 4H), 7.14 7.08 (m, 1H), 6.30 (dt,
48.3, 4.0 Hz, 1H), 4.05 (s, 3H), 2.32 (s, 3H), 2.24 (s, 3H)
8.4 Hz, 2H), 7.39 7.29 (m, 4H), 7.19 7.08 (m, 1H), 6.56 (dt,
48.0, 4.4, 5.1, 4.8 Hz, 1H), 4.05 (s, 3H), 2.32 (s, 3H), 2.24 (s, 3H)
H] ) 7.41 (d, J 7.3 Hz, 3H), 7.37 7.28 (m, 4H), 7.14 7.08 (m, 1H), 6.57 (dt,
47.9, 5.1, 4.4 Hz, 1H), 4.07 (s, 3H), 2.32 (s, 3H)
7.27 (m, 7H), 7.14 7.08 (m, 1H), 6.30 (dt, J 48.1, 4.1 Hz, 1H),
4.07 (s, 3H), 2.32 (s, 3H)
H] ) 7.44 7.39 (m, 3H), 7.37 7.29 (m, 4H), 7.14
4.06 (s, 3H), 2.32 (s, 3H)
7.39 (m, 3H), 7.38 7.28 (m, 4H), 7.14
+
5
Cl CH3 4-OCF2CHFCl
H
65
115
137
119
oil
−
−
−
116 515 ([M
−
H] ) 7.55 (d, 2H), 7.31−
+
18a
18b
18c
18d
18e
Cl Cl
4-OCF2CHFBr
H
H
H
H
H
H
H
H
H
H
68
72
58
72
82
140 581 ([M] )
−
−7.08 (m, 1H), 6.56 (dt,
)
)
+
Cl CH3 4-OCF2CHCl2
Cl CH3 4-OCF2CHFCF3
120 534 ([M
550 ([M
+
−
+
+
−
−
+
Cl Cl
4-OCF2CHFCl
135−
138 535 ([M] )
−
−
)
)
+
Cl CH3 4-OCF2CHFBr
Cl CH3 3-OCF2CHFCl
oil
562 ([M
+
−
−
)
−
−
−
)
+
18f
H
H
78
oil
516 ([M] )
−
−7.29 (m, 1H),
−
−
)
+
18g
18h
19a
19b
19c
19d
19e
19f
Cl CH3 4-OCF2CHFCl
Cl CH3 4-OCF2CHFBr
Cl CH3 4-OCF2CHFBr
Cl CH3 4-OCF2CHFCl
Cl CH3 4-OCF2CHFCF3
Cl CH3 4-OCF2CHCl2
Cl CH3 4-OCFCCl2
H
H
H
H
H
H
H
H
H
CH3
CH3
H
90
80
70
71
44
53
10
65
74
140−
142 530 ([M] )
7.50−
−
−
J
)
+
121−
124 576 ([M
560 ([M
+
+
+
+
+
+
+
+
H] ) 7.48 (d, J
)
−
−
J
)
+
foam
oil
)
−
−
J
−
)
+
H
516 ([M
H] ) 7.43
−
)
+
H
oil
549 ([M
−
−
−
7.08 (m, 1H), 5.03 (m, 1H),
7.08 (m, 1H), 5.95 (t,
+
H
114−
116 532 ([M
H] ) 7.42
−
−
−
J
−
)
4.8, 4.4 Hz, 1H), 4.07 (s, 3H), 2.32 (s, 3H)
7.38 (m, 3H), 7.37 7.29 (m, 2H), 7.17 7.08 (m, 3H), 4.06 (s, 3H),
+
H
oil
512 ([M
H] ) 7.42
−
−
2.31 (s, 3H)
+
Cl CH3 4-OCF2CHFCl
Cl CH3 4-OCF2CHFBr
CH3
CH3
123−
124 530 ([M
127 576 ([M
H] ) 7.38
−
7.27 (m, 4H), 7.24 (d, J
48.3, 4.0, 4.4, 3.7 Hz, 1H), 4.06 (s, 3H), 2.36 (s, 3H), 2.14 (s, 3H)
7.26 (m, 4H), 7.24 7.23 (m, 2H), 7.13 7.07 (m, 1H), 6.57 (dt,
) 48.0, 4.0, 5.1, 4.4 Hz, 1H), 4.06 (s, 3H), 2.36 (s, 3H), 2.14 (s, 3H)
) 2.2 Hz, 2H), 7.13−7.07 (m, 1H), 6.30 (dt,
J
−
)
+
19g
123−
H] ) 7.38
−
−
J
a See Figure 4 for structures. b Electron-impact ionization.
Table 4. Microanalytical and High-Resolution Mass Spectral (HRMS) Data for Compounds in Table 3
compd
molecular formula
% C (theory)
43.51 (43.40)
% H (theory)
2.10 (2.08)
% N (theory)
7.11 (7.23)
HRMS (theory)
5
C
22H15Cl2F4N3OS
21H12BrCl2F4N3OS
22H15Cl3F3N3OS
23H15ClF7N3OS
21H12Cl3F4N3OS
22H15BrClF4N3OS
22H15Cl2F4N3OS
23H17Cl2F4N3OS
23H17BrClF4N3OS
22H15BrClF4N3OS
22H15Cl2F4N3OS
23H15ClF7N3OS
22H15Cl3F3N3OS
22H14Cl3F2N3OS
23H17Cl2F4N3OS
23H17BrClF4N3OS
515.0250 (515.0249)
18a
18b
18c
18d
18e
18f
18g
18h
19a
19b
19c
19d
19e
19f
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
530.9950 (530.9954)
549.0504 (549.0513)
46.99 (46.99)
47.19 (47.12)
2.25 (2.31)
2.80 (2.70)
7.83 (7.69)
7.32 (7.49)
515.0246 (515.0249)
51.79 (52.09)
48.04 (48.06)
47.35 (47.12)
50.45 (51.18)
50.36 (50.24)
49.29 (49.60)
51.22 (51.53)
51.92 (52.09)
47.86 (48.06)
3.26 (3.23)
2.98 (2.98)
2.78 (2.70)
3.01 (2.93)
3.01 (2.75)
2.84 (2.84)
3.13 (2.75)
3.31 (3.23)
2.91 (2.98)
7.73 (7.29)
7.26 (7.31)
7.36 (7.49)
7.86 (8.14)
7.39 (7.64)
7.70 (7.89)
8.01 (8.19)
7.70 (7.92)
7.07 (7.31)
19g
Insecticidal Test for Tobacco Budworm (Heliothis Wirescens), Beet
Armyworm (Spodoptera exigua), and Cabbage Looper (Trichoplusia
ni). To prepare the test solution, the test compound was formulated at
400 ppm in 7.5 mL of 2:1 acetone/distilled water. Two hundred and
fifty microliters of the test solution was pipetted upon the surface of 8
mL of lepidopteran diet (Multispecies diet, Southland Products, Lake
Village, AR) contained in each of five 1 oz plastic cups (one cup ) 1
replication). A second-instar beet armyworm was placed upon the
treated diet in each cup once the solvent had air-dried. The solutions
remaining after completing applications to the 1 oz cups were then
used as leaf-dip solutions for 3.5 cm leaf disks cut from cabbage leaves
and cotton cotyledons. Five disks of each type of plant were dipped
until thoroughly coated into each rate of each compound ()5 replica-
tions of each treatment). After air-drying, the treated leaf disks were
placed individually into 1 oz plastic cups. Each dried, treated cotton
cotyledon disk was infested with a second-instar tobacco budworm
larva, and each cabbage leaf disk was infested with a second-instar
cabbage looper larva. Cups containing the treated substrates and larvae
were capped and then held in a growth chamber at 25 °C, 50-55%
relative humidity (RH), and 14 h light/10 h dark for 5 days. The number
of dead insects of five per species per treatment was then determined,

7522 J. Agric. Food Chem., Vol. 55, No. 18, 2007
Cudworth et al.
cabbage
Table 5. Greenhouse Laboratory Data To Demonstrate SAR Trends
cotton
aphida
green
peach aphidb
two-spotted
spider mitec
tobacco
budwormd
beet
armywormd
entry
ID
Y
R1
R2
R3
R4
looperd
3-Position Thiophene Substitution
1
2
3
4
12a
12p
Cl
Cl
Cl
CH3
Cl
H
4-OCF3
4-OCF3
4-OCF3
H
H
H
H
H
H
0.5 (12.8)e
78/80
72/47
13.7
65
9.6
<0.04 (0.151)
225
62
122
<1.6
(<1.6)
49.9 (59.9)
<1.6
4.02 (69.2)
20.6 (27.7)
100
0
C-to-D-Ring Connection (4- versus 5-Position)
4
5
4
3
Cl
Cl
CH3
CH3
4-OCF3
4-OCF3
H
H
H
H
0.5 (12.8)
0.07 (22.2)
13.7
23.3
<0.04 (0.151)
<0.293
225
>400
<1.6
21.9 (243)
<1.6
15.8
D-Ring Mono- versus Disubstitution
6
7
8
9
4
Cl
Cl
Cl
Cl
Cl
CH3
CH3
CH3
CH3
CH3
4-OCF3
3-Cl
3-F
2-F
3-F
H
H
H
H
H
H
0.5 (12.8)
9.28
4.41 (22.3)
4.93
13.7
55
88
91
89
<0.04 (0.151)
225
0/0
20/20
20/20
19.4
<1.6
60/0
60/0
100/0
65 (323)
<1.6
100/60
100/40
100/40
30.2 (40.3)
12h
12q
12r
12s
4-F
4-F
4-Cl
4-Cl
100
100
100
100
10
0.923 (933)
Fluoroalkyl Ethers
11
12
13
14
15
16
4
5
18a
18d
18e
18f
Cl
Cl
Cl
Cl
Cl
Cl
CH3
CH3
Cl
Cl
CH3
CH3
4-OCF3
H
H
H
H
H
H
H
H
H
H
H
H
0.5 (12.8)
<5.0
51/54
69/72
92/89
89/91
13.7
<3.1
70
78
62
<0.04 (0.151)
<0.1 (2.07)
225
<1.6
53.7
<1.6
3.93
<1.6
<1.79
<1.6
<1.6
2.17
23.1
<1.6
<1.6
<1.6
<1.6
<1.6
<1.6
4-OCF2CFCl
4-OCF2CFBr
4-OCF2CFCl
4-OCF2CFBr
3-OCF2CFCl
75
0
0
75
75
4.38 (151)
a Percent mortality of CA at 50/5 ppm. b Percent mortality of GPA at 50 ppm. c Percent mortality of TSSM at 2.5 ppm. d Percent mortality of BAW, CL, and TBW at
400/25 ppm. e LC50 or (LC90) in ppm.
Table 6. Laboratory Dataa for Phenyl Thiophen-2-yl Triazoles and
Commercial Standards
were placed on eight 2.2 cm leaf disks of cotton leaf, allowed to oviposit
over 24 h, and thereafter removed. The leaf disks were sprayed with a
100 ppm test solution using a hand syringe and then were allowed to
dry with 16 disks left untreated as a negative control. Disks were placed
on an agar substrate and held at 24 °C and 90% RH for 6 days. Percent
control based on the number of hatched larvae on treated disks and the
number on untreated disks is reported in Tables 5 and 6 and Supporting
Information Tables 1 and 2.
two-
spotted
spider
mite
green
peach
aphid
beet
army-
worm
cotton
aphid
tobacco
budworm
cabbage
looper
compd
3 (4-phenyl)
4 (5-phenyl)
5 (5-phenyl)
19b (4-phenyl)
cypermethrin
1
0.0656
0.5
<5.0
<5
23.3
13.7
<3.1
<5
<0.293
<0.04
<0.1
>400
225
<1.6
4.38
1.3
21.9
<1.6
<1.6
1.56
1.6
15.8
<1.6
<1.6
<1.56
0.6
Insecticidal Test for Sweetpotato Whitefly (Bemisia tabaci). Four
milligrams of each test compound was dissolved by adding 4 mL of
90:10 acetone/ethanol to the vial containing the sample compound. This
solution was added to 16 mL of water containing 0.05% Tween 20
surfactant to produce 20 mL of a 200 ppm spray solution. Five-week-
old cotton plants reared in a greenhouse were stripped of all foliage
except for the two uppermost true leaves that were >5 cm in diameter.
These plants were then placed into a laboratory colony of whiteflies
for 2 days for oviposition by the colony females. All whiteflies were
then removed from the test plants with pressurized air. The spray
solution was then applied to the test plants with a hand-held syringe
fitted with a hollow cone nozzle. One milliliter of spray solution was
applied to each leaf top and bottom for a total of 4 mL per plant. Four
replications of each test compound utilized a total of 16 mL of spray
solution. Plants were air-dried and then placed in a holding chamber
(28 °C and 60% RH) for 13 days. Compound efficacy was evaluated
by counting, under an illuminated magnifying glass, the number of
large nymphs (third/fourth instar) per leaf. Percent control based on
reduction of large nymphs of a test compound compared to solution-
only (no test compound) sprayed plants is reported in Supporting
Information Tables 1 and 2.
<2.5
0.7
65
0.05
0.8
1.7
0.29
14
spinosad
imidacloprid
0.8
1.3
0.1
a LC50 in ppm.
and the results are given in Tables 5 and 6 and Supporting Information
Tables 1 and 2.
Insecticidal Test for Cotton Aphid (Aphis gossypii). To prepare
spray solutions, 1 mg of each test compound was dissolved into 1 mL
of 90:10 acetone/ethanol. One milliliter of this chemical solution was
added to 19 mL of water containing 0.05% Tween 20 surfactant to
produce a 50 ppm spray solution.
One-week-old Crookneck squash plants, trimmed to one cotyledon
per plant, were infested with cotton aphid (all life stages). Prior to
spraying (16-20 h), sections of heavily infested colony squash leaves
were placed on the untreated squash cotyledons. As the infested sections
dried out, the aphids moved to the succulent plant material. Plants were
examined for good infestation prior to application. A hand-held
Devilbiss, air-brush sprayer was used to apply compound spray solution
to the squash plants. The plants were sprayed individually until runoff
on all sides. Then, all four plants of that treatment were sprayed with
a sweeping action with the remaining solution until completely used.
Each rate was applied to four plants (1 plant ) 1 replication). The
plants were allowed to air-dry and held for 3 days in a controlled room
at 26 °C and 40% RH prior to grading. Evaluation was by actual live
count using a dissecting microscope. Percent control was calculated
by comparison of test counts to solution-only (no test compound)
sprayed plants. Results are given in Tables 5 and 6 and Supporting
Information Tables 1 and 2.
RESULTS AND DISCUSSION
SAR Development Rationale for Phenylthiophenes. To find
the best chewing and sap-feeding insect pest coactive, different
areas of the phenylthiophenes were varied (Figure 2). Previous
work in the 2,6-dihalo area has demonstrated that, in general,
2,6-dihaloaryl A-rings (typically, difluorophenyl or chlorofluo-
rophenyl) are the most active. An N-methyl 1,2,4-triazole is the
B-ring of choice, as demonstrated in earlier work in the dihalo
area. The greatest points of diversity were incorporated on the
C-ring thiophene and the D-ring. The only constant was the
connection between the B- and C-rings: the 2-position of the
thiophene. Substitutions on the 3-position of the thiophene
Insecticidal Test for Two-Spotted Spider Mite (Tetranychus
urticae). Ovicide Method. Ten adult female two-spotted spider mites

Dihalophenyl Triazoles as Insecticides and Acaricides
J. Agric. Food Chem., Vol. 55, No. 18, 2007 7523
Scheme 2.
General Synthetic Routes to the Four-Ring Phenyl
Thiophen-2-yl Triazolesa
Figure 2. Determining structural requirements to maximize spectrum of
activity and efficacy.
Scheme 1.
General Synthetic Route to the ABC-Rings of
Thiophen-2-yl Triazolesa
included methyl, as on 1, chloro, as on 7, and a proton. The
D-ring was positioned at either the 4- or 5-position of the
thiophene ring, providing the extended lipophilicity needed for
lepidopteran activity. Heteroaryl and substituted aryl groups
were incorporated into the molecules, generally by Suzuki cross-
coupling methods. Variations in substitution pattern were
examined (ortho, meta, and para substituents), as well as number
of substituents (mono- and disubstitution), to evaluate steric
requirements for activity. Electronic requirements for activity
were evaluated by varying the substituents from electron-
withdrawing to electron-donating (for example, OCF3, CF3, CH3,
and OEt). Finally, substituted cycloalkyl and cycloalkenyl
groups were installed as D-rings to determine if the extended
lipophilicity demanded aromatic functionality. In this way, the
molecules were systematically varied to maximize efficacy and
spectrum of activity against both chewing and sap-feeding insect
pests.
Synthetic Strategy and Execution. The substituted thiophen-
2-yl triazoles were synthesized by the general routes shown in
Schemes 1 and 2. The acid chloride of a 2-thiophenecarboxylic
acid 8 was formed by reaction of the acid with thionyl chloride
and catalytic DMF in refluxing DCE. This intermediate was
then allowed to react with either N′-[(2,6-difluorophenyl)-
iminomethyl]-N-methylhydrazine carboxylic acid tert-butyl ester
in refluxing toluene or 2-chloro-6-fluorothiobenzimidic acid
methyl ester hydrogen bromide or methyl sulfate in DCE at
ambient temperature to generate the intermediate amide. Cy-
clization with methylhydrazine provided the three-ring system
9, containing a dihalogenated A-ring, N-methyl triazole B-ring,
and thiophene C-ring (Scheme 1). Bromination of the C-ring
thiophene could be effected in either the 4-position or the 4-
and 5-positions (in the case of methyl only), depending upon
the temperature of the reaction, to afford the corresponding
mono- (10) and dibrominated thiophenes (not shown, Scheme
2). The monobrominated thiophenes 10 could then be converted
to the four-ring compounds 12 via classical Suzuki cross-
coupling conditions, to furnish compounds such as 4 (R1 )
CH3, R2 ) 4-OCF3, R3, R4 ) H, Scheme 2), with or without
further functionalization. Alternatively, the dibrominated thiophene
could be subjected to metal-halogen exchange followed by
reaction with an electrophile (water, iodomethane, etc.) to give
1 (R4 ) H) or 11 (R4 ) CH3). Compound 1 or 11 could be
further elaborated via a variety of chemical conditions (Suzuki
cross-coupling, bromination, alkylation, reduction, or substitu-
tion conditions) to provide the 4-phenyl compounds 13, includ-
ing 3 (R1 ) CH3, R2 ) 4-OCF3, R3, R4 ) H, Figure 1).
Most of the compounds in Supporting Information Tables 1
and 2 were synthesized by the routes shown in Schemes 1 and
2. Representative examples of the synthetic steps within the
sequences can be found under Materials and Methods.
Some thiophene substitution patterns were difficult to achieve
by the routes given in Schemes 1 and 2. As a result, less
convergent synthetic sequences were needed. In the case of the
electron-deficient 3-chlorothiophene-2-carboxylic acid (8, R1
) Cl, Scheme 1), it was necessary to functionalize the thiophene
prior to completing the synthesis. Attempts to dibrominate the
three-ring system 9 (R1 ) Cl, Scheme 2) were unsuccessful,
yielding only the monobrominated product 10 (R1 ) Cl, R4 )
H) under a variety of stringent bromination conditions. Com-
mercially available 3-chlorothiophene-2-carboxylic acid (8) was
esterified via the acid chloride, and was brominated and
saponified, yielding the fully functionalized 4,5-dibromo-3-
chlorothiophene-2-carboxylic acid (14) in reasonable yield after
four steps (Scheme 3). Formation of the corresponding acid
chloride and reaction of it with 2-chloro-6-fluorothiobenzimidic
acid methyl ester methyl sulfate yielded the amide, which was
cyclized to the N-methyl triazole with methylhydrazine in
modest yield. A competing reaction of the methylhydrazine with
the 5-position bromine accounted for the less than optimal
cyclization yield. Suzuki coupling of bromide 15 under standard
conditions, although different from those in Scheme 2, provided
the four-ring compounds 16 (R ) OCF3, CF3, OEt) in reasonable
yields.
Given that the most active compounds tended to contain the
electron-withdrawing trifluoromethoxy group, the SAR around

7524 J. Agric. Food Chem., Vol. 55, No. 18, 2007
Cudworth et al.
mark of Dow AgraSciences LLC) Termite Colony Elimination
System, Figure 3). Thus, the ethyl group was removed from
the ethyl phenyl ether 12 or 13 with boron tribromide in
dichloromethane to provide the phenol, which was subsequently
alkylated with base and gaseous bromo- or chlorotrifluoroeth-
ylene or hexafluoropropene, to afford the desired perhaloalky-
lether 18 or 19 (Scheme 4). These compounds proved to be
even more active than their predecessors in this series (for
example, 4). Included in this latter group is 5 (Figure 5), a
field testing candidate in the northern hemisphere in the summer
of 2001. Further elaboration, like bromination, could be ac-
complished under standard conditions to yield 20.
Biological Activity, SAR Trends, and Field Results. Tables
1 and 2 in the Supporting Information provide greenhouse
laboratory data against tobacco budworm (TBW), beet army-
worm (BAW), cabbage looper (CL), cotton aphid (CA), two-
spotted spider mite (TSSM), and whitefly (WF). Table 5 was
created to compare and contrast major points of the SAR of
the phenyl thiophen-2-yl triazoles, including substitution on the
C-ring thiophene (3-position R group), C-to-D-ring connectivity
(4- vs 5-position aryl), and D-ring substitution (mono- vs
disubstitution, electron-withdrawing vs electron-donating sub-
stituents). Figure 4 provides the general structures for the
following tables.
Figure 3. Structurally relevant perhaloalkyl ether compounds.
Figure 4. General structures for compounds from Tables 5 and 6.
By comparison of the efficacy and spectrum of activity of
the compounds, the following SAR trends were established. The
3-position C-ring thiophene substitution adheres to the follow-
ing: CH3 > Cl > H . Ph (entries 1-3; some data not shown).
5-Position C-to-D-ring connectivity was preferred over the
4-position D-rings (entries 4 and 5). Monosubstituted D-rings
were preferred over disubstituted D-rings, with the para position
being favored over the ortho and meta positions (entries 6-10).
Electron-withdrawing groups generally had the best activity
(e.g., 4); however, increasing the number of halogens, as in 5,
increased the lepidopteran activity over that of the testing
candidate 4 (entries 11-16). These SAR trends are shown
pictorially in Figure 5.
Table 6 provides laboratory data (LC50 in ppm) for the
leading phenyl thiophen-2-yl triazoles in comparison to other
testing candidates, field testing candidates, and commercial
standards. In the laboratory, compound 5 has activity comparable
to that of other field testing molecules. All three boldfaced
compounds show activity comparable to those of commercial
standards with superior activity against mites.
Figure 5. Pictorial summary of SAR trends.
Scheme 3. Synthetic Route to Phenyl Thiophen-2-yl Triazolesa
Extending the lipophilicity of the first-generation dihalo
actives provided the desired lepidopteran activity in the phe-
nylthiophene series while retaining the sap-feeding insect pest
activity. SAR development afforded the first lead compound,
4, which was selected for field testing. It was also observed
that attachment of the D-ring phenyl systems was preferred at
the 5- as compared to the 4-position. Subsequent exploration
revealed that perhaloalkyl ethers in the para position of the
D-ring gave optimal efficacy and, in particular, chlorotrifluo-
roethyl ether derivative 5 stood out as the best and was sent for
advanced field testing. Although these compounds were highly
active in laboratory tests, their activity in the field was not
sufficient to warrant any further advancement. Although the
phenyl thiophen-2-yl triazole series afforded exciting activity,
the corresponding phenyl thiophen-3-yl triazoles, as well as other
nitrogen heterocycles/bioisosteres for triazoles, were also in-
vestigated and will be the subject of subsequent publications.
the D-ring was expanded by generating perhaloalkyl ethers
similar to that found in hexaflumuron (17, {N-[[[3,5-dichloro-
4-(1,1,2,2-tetrafluoroethoxy)phenyl]amino]carbonyl]-2,6-difluo-
robenzamide}, the active ingredient in Recruit II (trademark of
Dow AgraSciences LLC) termite bait in the Sentricon (trade-
ABBREVIATIONS USED
1, 5-(4-bromo-3-methylthiophen-2-yl)-3-(2-chloro-6-fluo-
rophenyl)-1-methyl-1H-[1,2,4]triazole; 2, 3-(2-chloro-6-fluo-

Dihalophenyl Triazoles as Insecticides and Acaricides
J. Agric. Food Chem., Vol. 55, No. 18, 2007 7525
Scheme 4. Synthetic Sequence for Generating Perhaloalkylethersa
rophenyl)-5-[3,4-dichloro-5-(4-ethoxyphenylethynyl)thiophen-
2-yl]-1-methyl-1H-[1,2,4]triazole; 3, 3-(2-chloro-6-fluorophenyl)-
1-methyl-5-[3-methyl-4-(4-trifluoromethoxyphenyl)thiophen-2-
yl]-1H-[1,2,4]triazole; 4, 3-(2-chloro-6-fluorophenyl)-1-methyl-
5-[3-methyl-5-(4-trifluoromethoxyphenyl)thiophen-2-yl]-1H-
[1,2,4]triazole; 5, 3-(2-chloro-6-fluorophenyl)-5-{5-[4-(2-chloro-
1,1,2-trifluoroethoxy)phenyl]-3-methylthiophen-2-yl}-1-methyl-
1H-[1,2,4]triazole; 6, 2-chloro-5-[5-(2-chloro-6-fluorophenyl)-
2-methyl-2H-[1,2,4]triazol-3-yl]pyridine; 7, 3-(2-chloro-6-
fluorophenyl)-1-methyl-5-(3,4,5-trichlorothiophen-2-yl)-1H-
[1,2,4]triazole;9a,3-(2-chloro-6-fluorophenyl)-5-(3-chlorothiophen-
2-yl)-1-methyl-1H-[1,2,4]triazole;10a,5-(5-bromo-3-chlorothiophen-
2-yl)-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-
[1,2,4]triazole; 10b, 5-(5-bromo-3-chlorothiophen-2-yl)-3-(2,6-
difluorophenyl)-1-methyl-1H-[1,2,4]triazole; 11a, 5-(4-bromo-
3,5-dimethylthiophen-2-yl)-3-(2-chloro-6-fluorophenyl)-1-methyl-
1H-[1,2,4]triazole; 12a, 3-(2-chloro-6-fluorophenyl)-5-[3-chloro-
5-(4-trifluoromethoxyphenyl)thiophen-2-yl]-1-methyl-1H-
[1,2,4]triazole; 12b, 3-(2-chloro-6-fluorophenyl)-5-[3-chloro-5-
(4-trifluoromethylphenyl)-thiophen-2-yl}-1-methyl-1H-
[1,2,4]triazole; 12c, 3-(2-chloro-6-fluorophenyl)-5-(3-chloro-
5-p-tolylthiophen-2-yl)-1-methyl-1H-[1,2,4]triazole; 12d, 5-
[3-chloro-5-(4-ethoxyphenyl)thiophen-2-yl]-3-(2-chloro-6-fluo-
rophenyl)-1-methyl-1H-[1,2,4]triazole; 12e, 5-[5-(4-bromophe-
nyl)-3-chlorothiophen-2-yl]-3-(2-chloro-6-fluorophenyl)-1-methyl-
1H-[1,2,4]triazole; 12f, 3-(2-chloro-6-fluorophenyl)-5-[3-chloro-
5-(4-methylsulfanylphenyl)thiophen-2-yl}-1-methyl-1H-
[1,2,4]triazole; 12g, 3-(2-chloro-6-fluorophenyl)-1-methyl-
5-[3-methyl-5-(4-trifluoromethylphenyl)thiophen-2-yl]-1H-
[1,2,4]triazole; 12h, 3-(2-chloro-6-fluorophenyl)-5-[5-(3-
chloro-4-fluorophenyl)-3-methylthiophen-2-yl]-1-methyl-1H-
[1,2,4]triazole; 12i, 3-(2-chloro-6-fluorophenyl)-5-[5-(3-ethox-
yphenyl)-3-methylthiophen-2-yl]-1-methyl-1H-[1,2,4]triazole; 12j,
3-(2-chloro-6-fluorophenyl)-5-[5-(4-ethoxyphenyl)-3,4-dimeth-
ylthiophen-2-yl]-1-methyl-1H-[1,2,4]triazole; 12k, 3-(2-chloro-
6-fluorophenyl)-5-[3,4-dimethyl-5-(4-trifluoromethoxyphenyl)-
thiophen-2-yl]-1-methyl-1H-[1,2,4]triazole; 12l, 5-[3-chloro-5-
(4-trifluoromethoxyphenyl)thiophen-2-yl]-3-(2,6-difluorophenyl)-
1-methyl-1H-[1,2,4]triazole; 12m, 5-(3-chloro-5-p-tolylthiophen-
2-yl)-3-(2,6-difluorophenyl)-1-methyl-1H-[1,2,4]triazole; 12n,
5-[3-chloro-5-(4-ethoxyphenyl)thiophen-2-yl]-3-(2,6-difluorophe-
nyl)-1-methyl-1H-[1,2,4]triazole; 12o, 5-[3-chloro-5-(4-trifluo-
romethylphenyl)thiophen-2-yl}-3-(2,6-difluorophenyl)-1-methyl-
1H-[1,2,4]triazole; 13a, 3-(2-chloro-6-fluorophenyl)-5-[4-(4-
ethoxyphenyl)-3-methylthiophen-2-yl]-1-methyl-1H-
[1,2,4]triazole; 13b, 3-(2-chloro-6-fluorophenyl)-1-methyl-5-[3-
methyl-4-(4-trifluoromethylphenyl)thiophen-2-yl]-1H-
[1,2,4]triazole; 13c, 3-(2-chloro-6-fluorophenyl)-5-[4-(4-
isopropylphenyl)-3-methylthiophen-2-yl]-1-methyl-1H-[1,2,4]-
triazole; 13d, 3-(2-chloro-6-fluorophenyl)-5-[4-(4-ethoxyphe-
nyl)-3,5-dimethylthiophen-2-yl]-1-methyl-1H-[1,2,4]triazole; 13e,
3-(2-chloro-6-fluorophenyl)-5-[3,5-dimethyl-4-(4-trifluorometh-
ylphenyl)thiophen-2-yl]-1-methyl-1H-[1,2,4]triazole; 13f, 3-(2-
chloro-6-fluorophenyl)-5-[3,5-dimethyl-4-(4-trifluoromethox-
yphenyl)thiophen-2-yl]-1-methyl-1H-[1,2,4]triazole; 13g, 3-(2-
chloro-6-fluorophenyl)-5-[4-(4-isopropylphenyl)-3,5-
dimethylthiophen-2-yl]-1-methyl-1H-[1,2,4]triazole; 13h, 3-(2-
chloro-6-fluorophenyl)-5-[4-(4-chlorophenyl)-3,5-
dimethylthiophen-2-yl]-1-methyl-1H-[1,2,4]triazole; 14, 4,5-
dibromo-3-chlorothiophene-2-carboxylic acid; 15, 3-(2-chloro-
6-fluorophenyl)-5-(4,5-dibromo-3-chlorothiophen-2-yl)-1-methyl-
1H-[1,2,4]triazole;
16a,
5-[4-bromo-3-chloro-5-(4-
trifluoromethoxyphenyl)thiophen-2-yl]-3-(2-chloro-6-
fluorophenyl)-1-methyl-1H-[1,2,4]triazole; 16b, 5-[4-bromo-3-
chloro-5-(4-trifluoromethylphenyl)thiophen-2-yl]-3-(2-chloro-6-
fluorophenyl)-1-methyl-1H-[1,2,4]triazole; 16c, 5-[4-bromo-3-
chloro-5-(4-ethoxyphenyl)thiophen-2-yl]-3-(2-chloro-6-
fluorophenyl)-1-methyl-1H-[1,2,4]triazole; 17, N-{[[3,5-dichloro-
4-(1,1,2,2-tetrafluoroethoxy)phenyl]amino]carbonyl}-2,6-
diflubenzamide;18a,5-{5-[4-(2-bromo-1,1,2-trifluoroethoxy)phenyl]-
3-chlorothiophen-2-yl}-3-(2-chloro-6-fluorophenyl)-1-methyl-
1H-[1,2,4]triazole; 18b, 3-(2-chloro-6-fluorophenyl)-5-{5-[4-
(2,2-dichloro-1,1-difluoroethoxy)phenyl]-3-methylthiophen-2-
yl}-1-methyl-1H-[1,2,4]triazole; 18c, 3-(2-chloro-6-fluorophenyl)-
5-{5-[4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-methylthiophen-
2-yl}-1-methyl-1H-[1,2,4]triazole; 18d, 5-{3-chloro-5-[4-(2-
chloro-1,1,2-trifluoroethoxy)phenyl]thiophen-2-yl}-3-(2-chloro-
6-fluorophenyl)-1-methyl-1H-[1,2,4]triazole; 18e, 5-{5-[3-(2-
bromo-1,1,2-trifluoroethoxy)phenyl]-3-methylthiophen-2-yl}-3-
(2-chloro-6-fluorophenyl)-1-methyl-1H-[1,2,4]triazole; 18f, 3-(2-
chloro-6-fluorophenyl)-5-{5-[3-(2-chloro-1,1,2-
trifluoroethoxy)phenyl]-3-methylthiophen-2-yl}-1-methyl-1H-
[1,2,4]triazole; 18g, 3-(2-chloro-6-fluorophenyl)-5-{5-[4-(2-
chloro-1,1,2-trifluoroethoxy)phenyl]-3,4-dimethylthiophen-2-
yl}-1-methyl-1H-[1,2,4]triazole; 18h, 5-{5-[4-(2-bromo-1,1,2-
trifluoroethoxy)phenyl]-3,4-dimethylthiophen-2-yl}-3-(2-chloro-
6-fluorophenyl)-1-methyl-1H-[1,2,4]triazole; 19a, 5-{4-[4-(2-
bromo-1,1,2-trifluoroethoxy)phenyl]-3-methylthiophen-2-yl}-3-
(2-chloro-6-fluorophenyl)-1-methyl-1H-[1,2,4]triazole; 19b, 3-(2-
chloro-6-fluorophenyl)-5-{4-[4-(2-chloro-1,1,2-
trifluoroethoxy)phenyl]-3-methylthiophen-2-yl}-1-methyl-1H-
[1,2,4]triazole; 19c, 3-(2-chloro-6-fluorophenyl)-5-{4-[4-
(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-3-methylthiophen-2-yl}-
1-methyl-1H-[1,2,4]triazole; 19d, 3-(2-chloro-6-fluorophenyl)-
5-{4-[4-(2,2-dichloro-1,1-difluoroethoxy)phenyl]-3-
methylthiophen-2-yl}-1-methyl-1H-[1,2,4]triazole; 19e, 3-(2-

7526 J. Agric. Food Chem., Vol. 55, No. 18, 2007
Cudworth et al.
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Devries, D. H.; Denny, C. P.; Ash, M. L. (Dow AgroSciences
LLC). Preparation of 3-aryl-5-heterocyclyl-1,2,4-triazoles as
insecticides and acaricides. WO 200024739, 2000.
chloro-6-fluorophenyl)-5-{4-[4-(2,2-dichloro-1-
fluorovinyloxy)phenyl]-3-methylthiophen-2-yl}-1-methyl-1H-
[1,2,4]triazole; 19f, 3-(2-chloro-6-fluorophenyl)-5-{4-[4-(2-
chloro-1,1,2-trifluoroethoxy)phenyl]-3,5-dimethylthiophen-2-
yl}-1-methyl-1H-[1,2,4]triazole; 19g, 5-{4-[4-(2-bromo-1,1,2-
trifluoroethoxy)phenyl]-3,5-dimethylthiophen-2-yl}-3-(2-chloro-
6-fluorophenyl)-1-methyl-1H-[1,2,4]triazole; 20, 5-{5-bromo-
4-[4-(2-bromo-1,1,2-trifluoroethoxyphenyl]-3-methylthiophen-
2-yl}-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-
[1,2,4]triazole.
ACKNOWLEDGMENT
(11) Tisdell, F. E.; Pechacek, J. T.; Schoonover, J. R., Jr. Ripa, P.
V.; Dintenfass, L. P.; Gifford, J. M.; Martin, T. P.; Yap, M.;
Devries, D. H.; Ash, M. L. (Dow AgroSciences LLC). Prepara-
tion of 3-phenyl-5-cyclopropyl-1,2,4-triazoles as insecticides and
acaricides. WO 200024720 A1, 2000.
(12) Tisdell, F. E.; Johnson, P. L.; Pechacek, J. T.; Bis, S. J.; Hegde,
V. B.; Schoonover, J. R., Jr.; Ripa, P. V.; Dintenfass, L. P.;
Gifford, J. M.; Thibault, T. D.; Ash, M. L.; Devries, D. H.;
Martin, T. P. (Dow AgroSciences LLC). Preparation of pyridyl-
1,2,4-triazoles as acaricides and insecticides. WO 200024735
A1, 2000.
We thank Jeff Gilbert and Jeff Godbey for conducting HRMS
analyses.
Supporting Information Available: Greenhouse laboratory
data are provided for the phenyl 4- and 5-substituted thiophenes.
This material is available free of charge via the Internet at http://
pubs.acs.org.
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Received for review May 22, 2007. Revised manuscript received July
2, 2007. Accepted July 2, 2007.
JF071498S