Synthesis and herbicidal activity of novel N -(2,2,2)- trifluoroethylpyrazole derivatives

Article abstract of DOI:10.1021/jf9042166

A series of novel N-(2,2,2)-trifluoroethylpyrazole derivatives were synthesized, and their structures were characterized by IR, mass spectroscopy, ¹H NMR, and elementary analysis. The herbicidal activities of target compounds 10a?c and 11a?c we

Full text of DOI:10.1021/jf9042166

4356 J. Agric. Food Chem. 2010, 58, 4356–4360
DOI:10.1021/jf9042166
Synthesis and Herbicidal Activity of Novel
N-(2,2,2)-Trifluoroethylpyrazole Derivatives
HONG-J
U
MA
, YONG-HONG
L
I, QIAN-FEI
Z
HAO, TAO
Z
HANG, R
U
-LIANG
XIE,
X
IANG-DONG
MEI
,
AND UN ING
J
N
*
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese
Academy of Agricultural Sciences, Beijing 100193, China
A series of novel N-(2,2,2)-trifluoroethylpyrazole derivatives were synthesized, and their structures
were characterized by IR, mass spectroscopy, 1H NMR, and elementary analysis. The herbicidal
activities of target compounds 10a-c and 11a-c were assessed. The bioassay results showed that
these pyrazole derivatives exhibited good herbicidal activity. Compound 11a showed the best pre-
emergence herbicidal effects against both dicotyledonous and monocotyledonous weeds with good
safety to maize and rape at the dosage of 150 g a.i. ha-1 in greenhouse. Field trials indicated that
compound 11a exhibited better herbicidal activity by soil application than the commercial herbicide,
metolachlor. Moreover, compound 11a showed the same level of safety to maize as metolachlor.
KEYWORDS: N-(2,2,2)-Trifluoroethylpyrazole; herbicidal activity; synthesis; safety
Scheme 1. Design Strategy for the Target Compounds
INTRODUCTION
Much interest in pyrazole derivatives has been drawn in
agrochemicals because of their excellent bioactivity (1-8). Nume-
rous herbicides such as pyrazolate, pyrazoxyfen, benzofenap,
pyraflufen-ethyl, fluazolate, and pyrazosulfuron-ethyl with pyra-
zole moieties have been commercialized (9). Recently, a series of
new pyrazole derivatives with potential herbicidal activity have
been synthesized by Nakatani et al. (10, 11). The key feature of
these compounds is a five- or six-membered heterocycle attached
to the 4-position of the pyrazole ring by a thiomethylene or
sulfonylmethylene bridge. In the structure-activity relationship
(SAR) development around these compounds, the optimal struc-
ture with high herbicidal efficacy and selectivity against target
species contains a substituted pyrazole, which is attached to a
dihydroisoxazole bridged by thiomethylene or sulfonylmethylene.
Among them, 3-[[[5-(difluoromethoxy)-1-methyl-3-(trifluoro-
methyl)-1H-pyrazol-4-yl]methyl]sulfonyl]-4,5-dihydro-5,5-dimethyl-
isoxazole (code name KIH-485) is currently under commercial
development by Kumiai Chemical Industry Co., Ltd., as a pre-
emergence weed control for maize and soybean. The spectrum of
weeds controlled by KIH-485 is similar to the acetanilide herbi-
cides such as metolachlor and dimethenamid (12-15). KIH-485
is a potent inhibitor of very long-chain fatty acids (VLCFAs)
biosynthesis, similar to the K3 group of herbicides (16). Very
long-chain fatty acid elongase (VLCFAE)-inhibiting herbicides
have been categorized into the K3 group by the Herbicide
Resistance Action Committee, including metolachlor, naproani-
lide, flufenacet, etc.
thiomethylene or sulfonylmethylene (Scheme 1). Moreover, the
introduction of trifluoromethyl into N-methyl group of pyrazole
ring would be expected to improve herbicidal activity due to the
intrinsic properties of trifluoromethyl, such as high thermal
stability, increased lipophilicity, electronegativity, and relatively
small size (17). The synthesis and herbicidal activities of these
novel pyrazole derivatives are described in this paper.
MATERIALS AND METHODS
1H NMR spectra were recorded in CDCl3 with a Bruker
DPX300 spectrometer, using tetramethylsilane as an internal
standard (performed at China Agricultural University). Elemen-
tal analysis (C, H, and N) and electrospray ionization-mass
spectrometry (ESI-MS) were performed at the Institute of Chem-
istry, Chinese Academy of Sciences. IR (KBr) (vmax, cm-1
)
spectra were recorded on a Nicolet IR200 FT-IR spectrophoto-
meter. Melting points were measured ona WRS-2A melting point
apparatus and are uncorrected. The solvents and reagents were
used as received or were dried prior to use as needed.
Synthesis. Dihydroisoxazole was synthesized as described in the
patent (18) (Scheme 2). The synthetic route from acetylacetone (4) to
4-halo-5-((5,5-dimethyl-4,5-dihydroisoxazol-3-yl)sulfonylmethyl)-3-methyl-
1-(2,2,2-trifluoroethyl)-1H-pyrazole (11) is shown in Scheme 3.
To further explore the potential of this class of compounds as
herbicide candidates, we developed an idea that dihydroisoxazole
is attached to the 5-position of the pyrazole ring linked by
Hydroxyiminoacetic Acid (2). A mixture of aqueous glyoxylic acid
(213 g, 1.44 mol, 50%) and hydroxylamine hydrochloride (100 g, 1.44 mol)
was stirred at room temperature overnight. The reaction mixture was
*To whom correspondence should be addressed. Tel: þ86-10-
62899142. E-mail: jning502@yahoo.com.cn.
pubs.acs.org/JAFC
Published on Web 03/23/2010
© 2010 American Chemical Society

Article
J. Agric. Food Chem., Vol. 58, No. 7, 2010 4357
Scheme 2. Synthetic Route of Intermediate Compound 3
Scheme 3. Synthetic Route of Target Compounds
extracted with diethyl ether, and after it was dried over anhydrous
sodium sulfate, the solvent was removed in vacuo. The crude product
was recrystallized from acetonitrile to give 2 as colorless crystals (115 g,
89.7% yield).
Compounds 7b,c were synthesized using similar procedure by treating
compound 6 with N-bromosuccinimide (NBS) or N-iodosuccinimide
(NIS), respectively.
5-(Bromomethyl)-4-chloro-3-methyl-1-(2,2,2-trifluoroethyl)-
1H-pyrazole (8a). To a solution of compound 7a (16.85 g, 0.08 mol) in
carbon tetrachloride (300 mL) were added NBS (15.57 g, 0.087 mol) and a
catalytic amount of benzoyl peroxide (0.1 g). After it was refluxed for 0.5 h,
the reaction mixture was cooled to room temperature and filtered. The
filtrate was concentrated, and the resulting mixture was poured into water,
followed by extraction with dichloromethane. The combined organic
extracts were washed with brine, dried over anhydrous sodium sulfate,
and concentrated in vacuo. The residue was purified by column chroma-
tography on silica gel (ethyl acetate/hexane=1/20) to give compound 8a
(21.4 g) as a yellow liquid. Compounds 8b,c were synthesized via the
same procedures accordingly. Compound 8a, 62.5% yield. 1H NMR
(CDCl3, 300 MHz): δ 2.28 (s, 3H, CH3), 4.43 (s, 2H, CH2Br), 4.60 (dd, 2H,
CH2CF3, J=8.2, 8.3 Hz). Compound 8b, 59.5% yield. 1H NMR (CDCl3,
300 MHz): δ 2.26 (s, 3H, CH3), 4.44 (s, 2H, CH2Br), 4.62 (dd, 2H,
CH2CF3, J=8.2, 8.3 Hz). Compound 8c, 60.3% yield. 1H NMR (CDCl3,
300 MHz): δ 2.25 (s, 3H, CH3), 4.47 (s, 2H, CH2Br), 4.78 (dd, 2H,
CH2CF3, J=8.3, 8.3 Hz).
3-Chloro-5,5-dimethyl-4,5-dihydroisoxazole (3). A mixture of
compound 2 (36 g, 0.4 mol) and N-chlorosuccinimide (NCS) (108 g,
0.8 mol) in 1,2-dimethoxyethane (500 mL) was refluxed for 1 h. After
the mixture was cooled to 5 °C, potassium hydrogen carbonate (148 g,
1.48 mol) and water (18 mL) were added. 2-Methylpropene (45.3 g,
0.8 mol) was then introduced into the suspension over 20 min at 5 °C and
sealed. After it was stirred at room temperature for 24 h, the reaction
mixture was poured into water (500 mL) and then extracted with hexane
(2 ꢀ 100 mL). The combined organic extracts were washed with brine and
dried over anhydrous sodium sulfate. The solvent was removed in vacuo to
give 3 (19.82 g, 37% yield) as a yellow liquid without further purification.
1H NMR (CDCl3, 300 Hz): δ 1.46 (s, 6H), 2.93 (s, 2H).
3,5-Dimethyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole (6). To a solu-
tion of acetylacetone (16 mL) in water (100 mL), 2,2,2-trifluoroethylhy-
drazine (25 g, 70% in water) was added. After it was stirred for 5 min at
room temperature, 5 mL of concentrated hydrochloric acid was added and
stirred at 60 °C for 1.5 h. The reaction mixture was then treated with 1 N
sodium hydroxide solution to slightly basic (pH around 9). After this
mixture was extracted with dichloromethane (2 ꢀ 100 mL), the combined
dichloromethane solution was washed with saturated sodium hydrogen
carbonate solution and brine and dried over anhydrous sodium sulfate.
The solvent was removed in vacuo, and the resulting residue was passed
through a short silica gel column, eluting with dichloromethane. After
concentration, 36 g of crude desired product was obtained as a light yellow
liquid.
s-{4-Chloro-3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-5-yl}-
methyl Ethanethioate (9a). To a solution of compound 8a (21.4 g, 0.083
mol) in anhydrous ethanol (300 mL), potassium thioacetate (14.2 g, 0.124
mol) was added. After it was stirred at room temperature for 4 h, the
solvent was removed in vacuo, and the residue was poured into water,
followed by extraction with dichloromethane. The organic layer was
washed with brine and dried over anhydrous sodium sulfate. The solvent
was removed in vacuo, and the residue was purified by column chromato-
graphy on silica gel (ethyl acetate/hexane=1/18) to give compound 9a
(11.4 g) as a yellow liquid. Compounds 9b,c were synthesized via the same
4-Chloro-3,5-dimethyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole (7a).
A mixture of compound 6 (15.6 g, 0.088 mol) and NCS (17.6 g, 0.132 mol)
in acetone (500 mL) was irradiated under an ultrasonic wave in a 25-30 °C
bath for 8 h. The solution was concentrated, and the resulting residue was
passed through a short silica gel column, eluting with dichloromethane, to
give the crude product of compound 7a as an orange liquid (16.85 g).
1
procedures accordingly. Compound 9a, 54.3% yield. H NMR (CDCl3,
300 MHz): δ 2.21 (s, 3H, COCH3), 2.37 (s, 3H, CH3), 4.13 (s, 2H), 4.82 (dd,
2H, CH2CF3, J=9.0, 8.3 Hz). Compound 9b, 55.8% yield. 1H NMR
(CDCl3, 300 MHz): δ 2.21 (s, 3H, COCH3), 2.37 (s, 3H, CH3), 4.13 (s, 2H),

4358 J. Agric. Food Chem., Vol. 58, No. 7, 2010
Ma et al.
4.83 (dd, 2H, CH2CF3, J=8.5, 8.4 Hz). Compound 9c, 50.7% yield. 1H
NMR (CDCl3, 300 MHz): δ 2.22 (s, 3H, COCH3), 2.37 (s, 3H, CH3), 4.15
(s, 2H), 4.87 (dd, 2H, CH2CF3, J=8.4, 8.3 Hz).
[M þ Na]þ 396. Anal. calcd for C12H15ClF3N3O3S: C, 38.56; H, 4.04;
N, 11.24. Found: C, 38.60; H, 4.06; N, 11.20. Compound 11b, 69.5% yield;
mp, 158-160 °C. 1H NMR (CDCl3, 300 MHz): δ 1.51 [s, 6H, C(CH3)2],
2.28 (s, 3H, CH3), 2.99 (s, 2H, CCH2C), 4.76 (s, 2H, SCH2), 4.97 (dd, 2H,
CH2CF3, J=8.4, 8.4 Hz). IR (KBr, cm-1): 640.0, 1137.4, 1341.5, 2973.5.
ESI-MS [M þ Na]þ 440. Anal. calcd for C12H15BrF3N3O3S: C, 34.46; H,
3.62; N, 10.05. Found: C, 34.50; H, 3.51; N, 9.99. Compound 11c, 76.5%
yield; mp, 156-159 °C. 1H NMR (CDCl3, 300 MHz): δ 1.50 [s, 6H,
C(CH3)2], 2.27 (s, 3H, CH3), 2.99 (s, 2H, CCH2C), 4.76 (s, 2H, SCH2), 4.97
(dd, 2H, CH2CF3, J=8.4, 8.4 Hz). IR (KBr, cm-1): 644.7, 1125.3, 1340.1,
2974.4. ESI-MS [M þ Na]þ 487. Anal. calcd for C12H15IF3N3O3S: C,
30.98; H, 3.25; N, 9.03. Found: C, 30.88; H, 3.21; N, 9.11.
Inhibitory Effect of Compounds 10a-c and 11a-c on the Growth
of Weed Roots and Shoots. A mixture of agar powder (8 g) and distilled
water (1 L) was heated to melt and then cooled down to 40-50 °C. The
solution (0.2 mL) containing 10 g/L (acetone as solvent) testing compound
and melting agar (19.8 mL) was mixed, and this mixture was added into
plastic cups (Ø10 cm). The agar plate without test compound was used as
an untreated control. The seeds of Echinochloa crusgalli L., Digitaria
sanguinalis L., and Portulaca oleracea L. were put on the surface of the
agar plate. The cups were covered with glass lids, and the cultivations were
kept at 25 ( 1 °C, 50-55% relative humidity, and 12 h in the light and 12 h
in the dark alternatively for 7 days. The experiments were conducted in
three replicates. The lengths of root and shoot were measured after 7 days
of treatment, and the growth inhibitory rate related to untreated control
was determined. The commercial herbicide metolachlor was used as the
positive control.
4-Chloro-5-((5,5-dimethyl-4,5-dihydroisoxazol-3-yl)thiomethyl)-
3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole (10a). A mixture of
compound 9a (11.4 g, 0.04 mol), compound 3 (5.34 g, 0.04 mol), and
potassium carbonate (8.28 g, 0.06 mol) in anhydrous ethanol (250 mL) was
refluxed for 8 h. The reaction mixture was cooled and then poured into
water. The product was extracted with ethyl acetate, and the organic layer
was washed with brine and dried over anhydrous sodium sulfate. The
solvent was removed in vacuo, and the residue was purified by column
chromatography on silica gel (ethyl acetate/hexane=1/10) to give com-
pound 10a (7.98 g) as colorless crystals. Compounds 10b,c were synthe-
sized via the same procedures accordingly. Compound 10a, 58.0% yield;
mp, 77-78 °C. 1H NMR (CDCl3, 300 MHz): δ 1.40 [s, 6H, C(CH3)2], 2.23
(s, 3H, CH3), 2.77 (s, 2H, CCH2C), 4.26 (s, 2H, SCH2), 4.92 (dd, 2H,
CH2CF3, J=8.4, 8.3 Hz). IR (KBr, cm-1): 673.0, 1263.4, 2972.0. Anal.
calcd for C12H15ClF3N3OS: C, 42.17; H, 4.42; N, 12.29. Found: C, 42.18;
H, 4.48; N, 12.22. Compound 10b, 55.4% yield; mp, 75-77 °C. 1H NMR
(CDCl3, 300 MHz): δ 1.41 [s, 6H, C(CH3)2], 2.24 (s, 3H, CH3), 2.78 (s, 2H,
CCH2C), 4.26 (s, 2H, SCH2), 4.96 (dd, 2H, CH2CF3, J=9.0, 8.5 Hz). IR
(KBr, cm-1): 669.6, 1271.1, 2996.3. Anal. calcd for C12H15BrF3N3OS: C,
37.32; H, 3.91; N, 10.88. Found: C, 37.29; H, 3.82; N, 10.91. Compound
10c, 59.6% yield; mp, 77-78 °C. 1H NMR (CDCl3, 300 MHz): δ 1.41 [s,
6H, C(CH3)2], 2.24 (s, 3H, CH3), 2.77 (s, 2H, CCH2C), 4.26 (s, 2H, SCH2),
4.96 (dd, 2H, CH2CF3, J=8.4, 8.5 Hz). IR (KBr, cm-1): 669.6, 1271.0,
2992.1. Anal. calcd for C12H15IF3N3OS: C, 33.27; H, 3.49; N, 9.70. Found:
C, 33.29; H, 3.50; N, 9.66.
4-Chloro-5-((5,5-dimethyl-4,5-dihydroisoxazol-3-yl)sulfonylmethyl)-
3-methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole (11a). A mixture of
compound 10a (7.98 g, 0.023 mol) and m-chloroperbenzoic acid (12.4 g,
0.057 mol, 80%) in dichloromethane (250 mL) was stirred at room
temperature for 24 h. The reaction mixture was poured into water and
extracted with dichloromethane. The organic layer was washed with an
aqueous sodium hydrogen sulfite, sodium hydrogen carbonate, and brine
and dried over anhydrous sodium sulfate. The solution was concentrated,
and the solid residue was washed with hexane to afford compound 11a as a
colorless solid (6.86 g). Compounds 11b,c were synthesized via the same
procedures accordingly. Compound 11a, 79.3% yield; mp, 167-169 °C.
1H NMR (CDCl3, 300 MHz): δ 1.50 [s, 6H, C(CH3)2], 2.28 (s, 3H, CH3),
3.00 (s, 2H, CCH2C), 4.76 (s, 2H, SCH2), 4.96 (dd, 2H, CH2CF3, J=8.4,
8.3 Hz). IR (KBr, cm-1): 640.5, 1143.5, 1341.3, 2976.6. ESI-MS
Screening in Greenhouse Conditions. The seeds of test plants were
planted (0.6 cm depth) in plastic pots (200 cm2) containing clay loam soil.
Each test compound was dissolved in dimethylsulfoxide to give a 10 g/L
solution. Aqueous suspensions, prepared by diluting an emulsifiable
concentrate with water (containing 0.1% Tween 80) to a specified
concentration, were sprayed onto the surface of the soil using a micro-
sprayer at 1 day after planting. The plastic pots were placed at 22-25 °C in
a greenhouse. The fresh weights of aerial plant parts were measured 20
days later, and the percentage of inhibition relative to water-sprayed
controls was calculated. Commercial herbicide metolachlor was used as
the positive control. Three replicates were performed for each concentra-
tion. Monocotyledonous weeds such as E. crusgalli L. and D. sanguinalis
L. were used for the preliminary herbicidal screening test of compounds
10a-c and 11a-c at the dosage of 600 g a.i. ha-1. Four different kinds of
weeds such as D. sanguinalis L., Eleusine indica L., E. crusgalli L., and
P. oleracea L. were used for the advanced herbicidal screening test of
compound 11a, and the treatment dosages were 600, 300, and 150 g a.i. ha-1
.
Maize (Zea mays L. var. SHEN DAN 17) and rape (Brassica campestris
L. var. JING GUAN 1) were used for evaluating the crop selectivity of
compound 11a.
Field Trial. Field experiments were conducted in the experimental field
at Nankai University in July, 2009. The soil was a loam soil with a
composition of 1.1-1.3% organic matter, and the pH of the soil was
7.8-8.3. The experimental design area of plot was 20 m2, and four
replicates were performed for each concentration. The maize variety
SHEN DAN 17 was planted on July 9. The compound 11a was formulated
as a 20% suspension concentrate. Pre-emergence herbicide applications
were made to the soil surface within 24 h after maize planting at the dosages
of 300, 400, 600, and 800 g a.i. ha-1. The fresh weights of aerial plant parts
were measured 30 days later, and the percentage of inhibition relative to
water-sprayed control was calculated. Commercial herbicide 72% metola-
chlor EC (1404 g a. i. ha-1) was used as the positive control to compound
11a. Visual evaluations of crop injury were assessed on a scale of 0-100%,
with 0 representing no crop injury and 100 representing complete maize
death.
Figure 1. Crystal structure of compound 11a.
Scheme 4. Selective Bromination toward Intermediate 8

Article
J. Agric. Food Chem., Vol. 58, No. 7, 2010 4359
RESULTS AND DISCUSSION
pyrazole ring could be possibly substituted by bromine to gene-
rate monosubstituted products 8, 12, and the bis-substituted
product 13 (Scheme 4). To our delight, the bromination of
compounds 7a-c provided the desirable regioisomers 8a-c as
the major products in excellent isolated yields. Although it was
Synthesis. A series of N-(2,2,2)-trifluoroethylpyrazole deriva-
tives were synthesized including eight intermediates, 7a-c, 8a-c,
and 9b,c, and six target compounds, 10a-c and 11a-c. The
structures of these compounds were confirmed by 1H NMR. The
target compounds were further confirmed by IR, MS, and
elementary analysis. Compounds 11a,b were recrystallized by
slow evaporation from the acetone as solvent, and to confirm the
structures of these kinds of compounds, their single crystals were
analyzed by X-ray diffraction crystallography (19, 20). The
corresponding structure of compound 11a was shown in Figure 1.
In the synthesis of dihydroisoxazole, the intermediate dichloro-
oxime was not isolated. The crude compound was used directly
for the next step due to its unstability. During the preparation of
the target compounds 11a-c, the synthesis of the intermediates
8a-c was the key reaction, which is a free radical substitution
reaction. Both methyl groups at the 3-position and 5-position on
1
difficult to assign the structure of compound 8 by simple H
NMR analysis, the structure of compound 8 was inferred from
the final targets, while the final target 11a was confirmed by
single-crystal X-ray diffraction analysis.
Growth Inhibition of Weed Roots and Shoots. As shown in
Table 1, compounds 10a-c and 11a-c inhibited root and shoot
elongation of the germinated seed of weeds. Germination itself
was not strongly inhibited by these compounds. At 3 days after
treatment, the shoots and roots of the monocotyledonous weeds
were etiolated, followed by withering. The inhibitory activity
against P. oleracea L. showed no significant difference between
the metolachlor and the compounds synthesized.
Herbicidal Activity in Greenhouse Conditions. It can be seen
from Table 2 that all of the compounds showed better herbicidal
activities against monocotyledonous weeds in pre-emergence
treatment at the dosage of 600 g a.i. ha-1 than metolachlor.
When the linker was sulfonylmethylene, the corresponding
molecules (11a-c) had a higher inhibition rate for E. crusgalli
L. and D. sanguinalis L. It was also found that when the
substituent was chlorine at the 4-position of the pyrazole ring,
the corresponding compound 11a exhibited the best herbicidal
activity. The herbicidal activity of compound 11a was further
evaluated in a greenhouse (Table 3). Compound 11a showed
excellent inhibitory activity against both dicotyledonous and
monocotyledonous weeds, especially for monocotyledonous
Table 1. Inhibition of Compound 10a-c and 11a-c on the Growth of Weed
Roots and Shoots at 100 mg/L
relative inhibition (%)
E. crusgallia
D. sanguinalis
P. oleracea
compd
shoot
root
shoot
root
shoot
root
metolachlor
10a
10b
88 abb
88 ab
88 ab
89 b
80 bc
89 d
88 bc
93 d
92 b
98 c
62 a
54 a
54 a
62 a
54 a
62 a
62 a
74 b
75 b
80 b
81 b
63 a
80 b
75 b
86 cd
86 cd
62 a
93 d
97 c
98 c
10c
11a
91 cd
82 a
84 ab
81 a
89 a
88 a
90 ab
weeds even at a reduced rate of 150 g a.i. ha-1
.
11b
11c
74 b
63 a
85 ab
84 a
84 ab
Field Trial. Compound 11a held excellent herbicidal activity
against monocotyledonous and dicotyledonous weeds in field
trials. At 15 days after soil treatment, the injury symptoms against
monocotyledonous weeds included leaf browning and necrosis.
Dicotyledonous weeds exhibited severe symptoms of leaf crink-
ling and etiolating. As shown in Table 4, experimental data
showed that compound 11a achieved more than 95% of an
inhibition rate against monocotyledonous weeds at 30 days after
soil treatment, and there was no significant difference between the
different dosages of compound 11a and metolachlor. The inhibi-
tion rates of the fresh weights against P. oleracea L. reached 80,
85, 95, and 100% at the different dosages of 300, 400, 600, and 800
g a.i. ha-1, respectively. However, compound 11a showed a weak
effect to perennial weeds Convolvulus arvensis L.
Crop Safety. It was reported that KIH-485 provided good
efficacy on both grass and broadleaf weed species with excellent
selectivity in maize, wheat, and soybean (12-16). Compound 11a
showed comparable herbicidal activity in greenhouse conditions
and field trials. As shown in Table 3, compound 11a demon-
strated good safety to maize and rape, showing less than 2%
growth inhibition to maize and 12% growth inhibition to rape in
aE. crusgalli, Echinochloa crusgalli L.; D. sanguinalis, Digitaria sanguinalis L.;
P. oleracea, Portulaca oleracea L. b The treatments were grouped into statistically
distinct classes by applying analysis of variance (ANOVA) at P = 0.05 based on
Fisher’s LSD.
Table 2. Herbicidal Effect of Compounds 10a-c and 11a-c on Fresh
Weights against Monocotyledonous Weeds at 600 g a.i. ha-1 in Greenhouse
Conditions
relative inhibition (%)
compd
E. crusgallia
D. sanguinalis
metolachlor
10a
10b
66 ab
81 ab
82 bc
100 c
100 c
100 c
100 c
38 a
54 a
74 bc
54 ab
100 d
79 c
10c
11a
11b
11c
90 cd
aE. crusgalli, Echinochloa crusgalli L.; D. sanguinalis, Digitaria sanguinalis L.
b The treatments were grouped into statistically distinct classes by applying ANOVA
at P = 0.05 based on Fisher’s LSD.
Table 3. Herbicidal Activity and Selectivity of Compound 11a in Greenhouse Conditions
relative inhibition (%)
compd
metolachlor
11a
dosage (g a.i. ha-1
)
D. sanguinalisa
E. indica
E. crusgalli
P. oleracea
Z. mays
B. campestris
150
300
600
150
300
600
43 ( 6.3
76 ( 2.0
90 ( 0.8
86 ( 2.2
97 ( 2.3
100
84 ( 0.4
98 ( 3.8
97 ( 0.4
97 ( 2.7
99 ( 0.6
100
25 ( 1.1
39 ( 1.6
50 ( 1.6
100
36 ( 0.4
57 ( 1.3
60 ( 0.8
70 ( 1.5
97 ( 0.3
99 ( 1.4
1 ( 2.0
2 ( 1.7
2 ( 2.8
0
0
9 ( 1.9
11 ( 1.8
7 ( 1.6
12 ( 0.9
11 ( 2.4
100
100
0
1 ( 1.6
aD. sanguinalis, Digitaria sanguinalis L.; E. indica, Eleusine indica L.; E. crusgalli, Echinochloa crusgalli L.; P. oleracea, Portulaca oleracea L.; Z. mays, Zea mays L.;
B. campestris, Brassica campestris L.

4360 J. Agric. Food Chem., Vol. 58, No. 7, 2010
Ma et al.
Table 4. Herbicidal Activity and Safety of Compound 11a in a Maize Field at 30 Days after Soil Treatment
relative inhibition (%)
crop injuryc
compd
dosage (g a.i. ha-1
)
D. sanguinalisa
E. crusgalli
E. indica
monocotyledonous
P. oleracea
C. arvensis
Z. mays
300
400
95
98
100
100
100
100
100
97
98
98
99
99
97 ab
98 a
80
85
14
16
27
40
47
0
0
0
0
0
11a
metolachlor
600
800
100
100
95
99 a
95
100 a
98 a
100
100
1404
aD. sanguinalis, Digitaria sanguinalis L.; E. crusgalli, Echinochloa crusgalli L.; E. indica, Eleusine indica L.; P. oleracea, Portulaca oleracea L.; C. arvensis, Convolvulus
arvensis L.; Z. mays, Zea mays L. b The treatments were grouped into statistically distinct classes by applying ANOVA at P = 0.05 based on Fisher’s LSD. c Crop Injury, where 0
indicates no visible effect and 100 indicates complete death of maize.
greenhouse conditions. In field trials, compound 11a also showed
the same level of safety to maize as the commercial herbicide
metolachlor, and no visible injury was observed to the aerial parts
of maize (Table 4). A moderate selectivity was detected between
the inhibition of VLCFAEs from maize and the KIH-485-
sensitive plants. However, this weak selectivity could not explain
the selectivity in growth inhibition between maize and KIH-485-
sensitive plants. Other factors, such as detoxification of KIH-485
by glutathione S-transferase, might be involved in the observed
selectivity as referred according to the report of document (16).
The inhibition of VLCFAEs and the detoxification of glutathione
S-transferase might also be factors to the selectivity of compound
11a between crop and weed.
In summary, a series of N-(2,2,2)-trifluoroethylpyrazole deri-
vatives were synthesized, and their herbicidal activities were
evaluated. The herbicidal tests showed that when the dihydroi-
soxazole was attached to the 5-position of the N-(2,2,2)-trifluoro-
ethylpyrazole ring linked by thiomethylene or sulfonylmethylene,
the corresponding compounds presented good herbicidal activ-
ities. Especially compound 11a possessed excellent herbicidal
activity and selectivity to maize and rape and deserved further
studies on its biological efficacy, crop safety, and toxicity as the
herbicide candidate in a maize field.
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