Synthesis and evaluation of substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives as potent herbicidal agents

Article abstract of DOI:10.1016/j.bmc.2015.08.037

In an attempt to obtain novel candidate compound for weed control, a series of newly substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives 2 were designed and synthesized using compound II7 as a lead compound by Intermediate Derivatization Methods an

Full text of DOI:10.1016/j.bmc.2015.08.037

Bioorganic & Medicinal Chemistry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry
journal homepage: www.elsevier.com/locate/bmc
Synthesis and evaluation of substituted 3-(pyridin-2-yl)
benzenesulfonamide derivatives as potent herbicidal agents
⇑
Yong Xie, Hui-wei Chi, Ai-ying Guan, Chang-ling Liu , Hong-Juan Ma, Dong-liang Cui
State Key Laboratory of the Discovery and Development of Novel Pesticide, Shenyang Research Institute of Chemical Industry Co. Ltd, Shenyang 110021, China
a r t i c l e i n f o
a b s t r a c t
Article history:
In an attempt to obtain novel candidate compound for weed control, a series of newly substituted 3-(pyr-
idin-2-yl)benzenesulfonamide derivatives 2 were designed and synthesized using compound II7 as a lead
compound by Intermediate Derivatization Methods and their herbicidal activities were evaluated. The
herbicidal activity assay in greenhouse tests showed several compounds (2g, 2i, 2j, 2k, 2l, 2m, 2n and
Received 26 June 2015
Revised 17 August 2015
Accepted 26 August 2015
Available online xxxx
2o) exhibited significant herbicidal activity for controlling velvet leaf (Abutilon theophrasti medic.) and
youth-and-old age (Zinnia elegans jacq.) at 37.5 g a.i./ha. In particular, 2h was found to be the most poten-
tial candidate herbicide and was proved higher activity than the lead compound II7. The result of the
weed controlling spectrum test showed that 2h could effectively control dayflower (Commelina tuberosa),
bur beggarticks (Bidens tripartita linn.), youth-and-old age, cassia tora (Cassiaobtusifolia L.), velvet leaf,
purslane (Portulaca oleracea) and false daisy (Eclipta prostrata L.). In addition, the mixture of compound
Keywords:
Substituted 3-(pyridin-2-yl)
benzenesulfonamide compounds
Intermediate derivatization methods
Potent herbicidal agents
2h and propanil could produce a synergistic effect and enhance herbicidal activity. The result of the her-
bicidal activity assay in field test demonstrated that 2h could effectively control dayflower and night-
shade (Disambiguation) with long-lasting persistence. The present work indicates that 2h may be a
novel compound candidate as a potential herbicide.
Ó 2015 Published by Elsevier Ltd.
1
. Introduction
Herbicides are very effective in eliminating weed and are
2,6-diarylpyridine derivatives could be used as herbicide and defo-
liating agents. In previous works, we have reported the syntheses
of substituted 2-phenylpyridines derivatives using Intermediate
1
2–16
principally used in rice paddy, corn and wheat fields around the
world, playing a fundamental role in maximizing yield. However,
weeds continue to evolve resistance to all the known modes of her-
bicidal action, and no herbicide with a new target site has been
commercialized in nearly 20 years. Therefore, the number of tools
Derivatization Methods
in an attempt to obtain novel com-
1
pounds candidates for weed control, of which compound II7 gave
excellent herbicidal activities against velvet leaf, youth-and-old
age, barnyard grass and foxtail using herbicidal activity assay in
2
17
greenhouse tests, and showed better activity than oxyfluorfen
to manage weeds, and in particular those that can control
herbicide-resistant weeds, is diminishing rapidly.2 Much research
has focused on discovering novel compounds with structures
different from those of commercial herbicides.
and security to rice using herbicidal activity assay in field tests.18
In this paper, we designed and evaluated novel substituted
3-(pyridin-2-yl)benzenesulfonamide derivatives (Fig. 1 and Table 1)
using compound II7 as the leading compound in the search for new
herbicides with improved biological properties. As shown in
Figure 1, according to the terminal group replacement method
(TRM) which is a pronged approach of intermediate derivatization
Substituted 2-phenylpyridines which were firstly reported by
3
,4
Schaefer et al.
showed good herbicidal activity; several com-
pounds could efficiently control velvet leaf (Abutilon theophrasti),
redroot pigweed (Amaranthus retroflexus) and morningglory
1
2
methods, modification of the ethyl carbamate group of com-
(
Ipomoea subspecies) by the post-emergence method. Subse-
pound II7 by introducing ethyl glycinate and ethyl methylglycinate
which is the important group of the herbicide fluthiacet-methyl
5–10
19
quently, some patents and a literature
described fluorinated
2
-phenylpyridines that have been used as intermediates for drugs
and agrochemicals, such as substituted thiobarbituric acids and
-[(trifluoromethyl)pyridyl]phenols. Narabu et al.11 showed that
gave 2a and 2h. Then, 2b–2g and 2i–2u were further derived to
probe the structure–activity relationships. Furthermore, the herbi-
cidal effects of the substituted 3-(pyridin-2-yl)benzenesulfon-
amide derivatives were investigated in the greenhouse and the
field, and the weed controlling spectrum test and mixture of 2h
were evaluated.
4
⇑
Corresponding author. Tel.: +86 24 85869078; fax +86 24 85869137.
E-mail address: liuchangling@vip.163.com (C.-l. Liu).
http://dx.doi.org/10.1016/j.bmc.2015.08.037
968-0896/Ó 2015 Published by Elsevier Ltd.
0
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2
Y. Xie et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
F
Cl
N
N
N
S
O
S
O
Cl
S
Cl
S
Cl
R1
N
O
Cl
O
H
N
O
fluthiacet-methyl
R
O
O
O
O
N
N
O
3
F C
3
F C
"TRM"
II7
2
Figure 1. Design of the substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives 2. ‘TRM’ means ‘terminal group replacement method’.
Table 1
Chemical structures and herbicidal activity of 2a–2u by post-emergence treatment in greenhouse tests
Compd
R
1
R
YOApost- (g a.i./ha)
VELpost- (g a.i./ha)
FOXpost- (g a.i./ha)
BYGpost- (g a.i./ha)
6
00
150
37.5
600
150
37.5
600
150
37.5
600
150
75
37.5
2
2
2
2
2
a
b
c
d
e
H
H
H
H
H
OCH
NHCH
NHCH
N(CH
N(CH
2
CH
3
100
100
50
90
90
85
100
/
65
50
50
90
/
25
30
100
100
40
90
90
90
50
/
50
30
40
50
/
25
20
95
100
10
25
20
75
30
/
/
/
30
20
/
/
/
95
50
0
10
5
10
/
/
/
/
a
3
/
2
CH
3
/
/
/
3
)
2
2
CH
3
)
2
2
f
H
N
O
90
20
/
90
30
/
20
/
/
5
/
/
2
2
2
2
2
2
2
2
g
h
i
j
k
l
Me
Me
Me
Me
Me
Me
Me
Me
OH
OCH
OCH
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
95
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
95
100
100
90
80
95
95
90
95
60
95
70
40
95
80
60
70
30
90
30
/
95
30
30
15
95
98
80
85
80
75
75
70
20
98
30
40
60
35
30
35
10
95
10
/
40
/
2
CH
CF
3
100
100
90
100
95
2
3
OCH(CH
3
)
CH
OCH
OCH
C„CH
2
OCH
OCH
OCH
OCH
2
2
2
2
CH
2
2
2
2
2
CH
3
CH
CH
CH
3
m
n
2
CH
3
100
100
100
95
/
/
OCH
2
2
o
Me
100
100
100
100
100
85
95
70
30
60
50
/
O
2
2
p
q
Me
Me
NHCH
N(CH CH )
2 3 2
3
95
98
90
95
75
75
100
100
100
100
100
95
85
50
45
45
45
40
40
50
35
45
20
40
2
2
r
s
Me
Me
HN
NHC H
6 5
70
50
70
45
70
20
98
60
98
30
95
10
60
10
50
5
40
0
50
0
45
0
40
0
2
t
Me
HN
Cl
60
40
20
60
50
40
10
5
0
5
0
0
HN
2
u
Me
80
50
/
75
30
20
20
/
/
5
/
/
N
Cl
II7
100
100
100
100
100
100
100
100
80
100
100
85
YOApost-, VELpost-, FOXpost- and BYGpost- mean youth-and-old age (Zinnia elegans jacq.), velvet leaf (Abutilon theophrasti medic.), foxtail (Setaria glauca (L.) beauv), barnyard
grass (Echinochloa crus-galli (L.) beauv), respectively.
a
Stands for no data.
Cl
Cl
S
Cl
R1
N
O
Cl
Cl
SO
Cl
R1
N
O
Cl
Cl
(iii)
S
(
i)
(ii)
R
O
CH
3
2
Cl
O
2
O
2
N
N
N
F
3
C
N
3
F C
F3C
3
F C
2
b-2g, 2i-2u
1
2a R = H
1
2
h R = Me
1
Scheme 1. Overview of synthetic methods for 2a–2u. Reagents and conditions: (i) (a) 4-chlorophenylboronic, K
°C, 8 h; (ii) ethyl glycinate or ethyl methylglycinate, triethylamine, toluene 0 °C, 6 h; (iii) (a) NaOH, water/THF, 50 °C, 6 h; (b) corresponding alcohols or amine,
triethylamine, toluene, rt, 4 h.
2 3
CO , dimethoxyethane, reflux, 4 h; (b) chlorosulfonic acid,
0
2
. Chemistry
ethane with potassium carbonate as base, and chlorosulfonic acid
was added dropwise to the crude intermediate. Then, ethyl glyci-
nate and ethyl methylglycinate were used to synthesize 2a and
2h. 2a and 2h were treated with sodium hydroxide aqueous solu-
tion, and then the acidylated crude intermediates were treated
with the corresponding alcohols or amines in anhydrous
The preparation of substituted 3-(pyridin-2-yl)benzenesulfon-
amide derivatives 2a–2u is shown in Scheme 1. Intermediate 1
was synthesized from 2,3-dichloro-5-(trifluoromethyl)pyridine
with corresponding 4-chlorobezeneboronic in refluxing dimethoxy-
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Y. Xie et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
Table 2
3
tetrahydrofuran to give the other 19 terminal 2b–2g and 2i–2u.The
structures of compounds 2a–2u were confirmed by 1H NMR and
The weed controlling spectrum test of 2h by post-emergence treatment in
greenhouse tests
HRMS spectral data and element analyses.
Weeds
Control effect (%) (g a.i./ha)
3
.75
7.5
15
30
3
3
. Results and discussion
Barnyard grass
Foxtail
Crabgrass
20
40
10
50
70
70
80
90
80
80
30
40
20
55
80
80
85
95
90
85
30
50
40
60
80
85
85
98
95
95
40
50
50
75
80
90
95
98
98
98
.1. Herbicidal activity in greenhouse test
Dayflower
All the synthesized 2a–2u, including the previously reported
Bur beggarticks
Youth-and-old age
Cassia tora
Velvet leaf
Purslane
compound II7, were evaluated for their herbicidal ability to control
unwanted plants using post-emergence treatment in the green-
house. As shown in Table 1, the key compounds 2a and 2h which
were produced by introducing glycinate and ethyl methylglycinate
group to replace the ethyl carbamate group of the lead compound
II7 could efficiently control unwanted plants at the treatment con-
centration. In fact, 2h which showed 100%, 100%, 90%, 95% inhibi-
tion against velvet leaf, youth-and-old age, barnyard grass and
foxtail at 37.5 g a.i./ha, respectively, showed higher activity than
compound II7 which it mimicked, with 100%, 100%, 80%, 85% inhi-
bition against velvet leaf, youth-and-old age, barnyard grass and
foxtail at 37.5 g a.i./ha, respectively. For 2b–2f which were synthe-
sized through 2a, could not effectively control target plants at
False daisy
respectively,18 2h was less active but still demonstrated activity
with 30% and 50% inhibition against foxtail and barnyard grass at
15 g a.i./ha, respectively. Nonetheless, 2h could actually be an
important candidate compound because it can control cassia tora,
velvet leaf, purslane and false daisy efficiently and showed more
herbicidal activity than compound II7 for these four target plants
(unpublished work).
1
50 g a.i./ha except for compound 2b which showed 100% inhibi-
For the purpose of improving the lack of weed controlling spec-
trum and expanding the application range, the herbicidal activity
assay of 2h combined with propanil was completed. As shown in
Table 3, herbicidal activity can be improved because of the syner-
gistic effect between 2h and propanil. The mixed herbicide could
efficiently control the target weed and improved the lack of 2h.
For example, the mixture of 2h (24 g a.i./ha) and propanil
(1200 g a.i./ha) demonstrated significant activity with 100%, 70%,
95%, 100% and 80% inhibition against barnyard grass, foxtail, crab-
grass, velvet leaf and dayflower, whereas 2h (24 g a.i./ha) main-
tained 3%, 8%, 50%, 90% and 55% inhibition against barnyard
grass, foxtail, crabgrass, velvet leaf and dayflower, respectively,
and propanil (1200 g a.i./ha) exhibited 80%, 70%, 75%, 80% and 0
inhibition against barnyard grass, foxtail, crabgrass, velvet leaf
and dayflower, respectively.
tion against velvet leaf at 150 g a.i./ha and 90% inhibition against
velvet leaf at 37.5 g a.i./ha. Most compounds (2g and 2i–2u) which
were synthesized through 2h exhibited excellent herbicidal activ-
ity. In particular, compounds 2g, 2i, 2j, 2k, 2l, 2m, 2n and 2o, which
could efficiently control velvet leaf and youth-and-old age at
3
7.5 g a.i./ha and were roughly equivalent to compound II7 under
the same condition.
By comparison of herbicidal activity of 2a and 2h, 2e and 2q,
substitution with methyl as R
It seems that the substituent R
ever, the herbicidal activities of 2b and 2p could not give the same
prediction. Therefore, more compounds should be synthesized to
1
study substituent R . Hydroxy, alkoxy, alkylamino and arylamino
1
showed good herbicidal activity.
is a critical group for activity. How-
1
group were designed to infer the preliminary structure–activity
relationships of substituent R. Compounds 2h–2o with corre-
sponding alcohols as R showed excellent herbicidal activity against
velvet leaf and youth-and-old age, while 2s–2u with corresponding
amines as R almost lose the ability to control velvet leaf and youth-
and-old age. It seems to indicate that the corresponding alcohols as
R may play a pivotal role in herbicidal activity. However, the activ-
ities of 2p, 2q and 2r in which methylamino, diethylamino and
cyclopropylamino groups were introduced as R, respectively, differ
significantly. These three compounds could retain the ability to
control youth-and-old age and velvet leaf. It indicated that the sub-
stituent R containing an aromatic ring could result in the loss of
herbicidal ability (contrast 2p–2r and 2s–2u). The substituent R
could also influence the herbicidal activity for controlling barnyard
grass and foxtail. For example, 2h with ethoxyl as R could effi-
ciently control barnyard grass and foxtail, and 2i with a 2,2,2-tri-
fluoroethoxyl group lost the ability to control barnyard grass and
foxtail. Therefore, more compounds should be synthesized to doc-
ument the structure–activity relationships of substituent site R.
In order to understand the herbicidal ability of 2h, the weed con-
trolling spectrum test was performed in greenhouse. As shown in
Table 2, 2h could efficiently control dayflower, bur beggarticks,
youth-and-old age, cassia tora, velvet leaf, purslane and false daisy
with 75%, 80%, 90%, 95%, 98%, 98% and 98% inhibition at 30 g a.i./
ha, respectively. In particular, the herbicidal activity of 2h against
cassia tora, velvet leaf, purslane and false daisy could be satisfactory
and maintained 80% or better inhibition at 3.75 g a.i./ha. Compar-
ison with compound II7 which could effectively control foxtail and
barnyard grass with 100% and 100% inhibition at 18.5 g a.i./ha,
3.2. Herbicidal activity in field tests
Herbicidal activity results in field tests (Table 4) showed that 2h
at 30 g a.i./ha showed higher activity than bentazon (48%, water
dispersible granule) at 1440 g a.i./ha. The control effect of 2h at
30 g a.i./ha is 80% after 7 days of treatment and 85% after 15 days
of treatment, whereas the control effect of bentazon at 1440 g a.
i./ha is 70% after 7 days of treatment and 70% after 15 days of treat-
ment. This result also suggested that 2h could be an effective her-
bicide with long-lasting persistence. As well, 2h showed better
Table 3
Herbicidal activity of 2h combined with propanil by post-emergence treatment in
greenhouse tests
Concn
Control effect (%)
(g a.i./ha)
2h
Propanil Barnyard
Foxtail Crabgrass Velvet
leaf
Dayflower
grass
1
2
48
—
—
—
2
4
—
—
—
600
1200
2400
600
0
3
5
70
80
95
95
100
100
5
8
30
50
65
40
75
75
85
95
98
85
90
98
60
80
80
98
100
100
50
55
60
0
0
5
60
80
90
10
40
70
75
65
70
80
1
2
24 1200
48 2400
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4
Y. Xie et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
Table 4
combined methylene chloride phase was washed with water,
dried over sodium sulfate and evaporated. Yield: 70% of colorless
crystals of melting point 72–74 °C. H NMR (300 MHz, CDCl ) d
3 H
Herbicidal activity of 2h in field tests (Liaoning, China)
1
Compd
Concn (g a.i./ha)
Control effect to dayflower
and nightshade (%)
(ppm) = 7.47 (d, J = 8.3 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 8.04 (d,
7
days
15 days
J = 8.5 Hz, 1H), 8.05 (d, J = 8.3 Hz, 1H), 8.83 (s, 1H).
2
h
30
80
95
70
85
95
70
60
5.1.1.2. Synthesis of compound 1.
fonic acid was added dropwise to 3-chloro-2-(4-chlorophenyl)-5-
trifluoromethyl)pyridine (0.033 mol) at 0–5 °C, and the mixture
was heated at 130 °C for eight hours. The reaction mixture was
then cooled to room temperature and poured into crushed ice with
ethyl acetate (3 Â 60 mL), the combined extract was washed with
water, saturated brine, and dried over anhydrous magnesium sul-
The excessive chlorosul-
Bentazon
1440
(
3
activity than compound II7 to control dayflower and nightshade,
and by contrast, the control effect of compound II7 at 30 g a.i./ha
is 40% after 7 days of treatment and 40% after 15 days of
1
8
treatment.
fate, then filtered and concentrated under reduced pressure to give
1
a pale yellow liquid. Yield: 90%. H NMR (300 MHz, CDCl
3
) d
H
(
ppm) = 7.73 (d, J = 8.3 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 8.05 (d,
4
. Conclusion
J = 8.3 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.80 (s, 1H), 8.99 (s, 1H).
HRMS: m/z 411.8955 [M+Na] (calcd [M+Na] : 411.8957).
+
+
In summary, a series of newly substituted 3-(pyridin-2-yl)ben-
zenesulfonamide derivatives 2 were designed and prepared by
Intermediate Derivatization Methods and their herbicidal activities
were evaluated. 2g, 2i, 2j, 2k, 2l, 2m, 2n and 2o exhibited signifi-
cant herbicidal activity in controlling velvet leaf and youth-and-
old age at 37.5 g a.i./ha, using herbicidal activity assays in the
greenhouses. 2h in particular was found to be the best potential
candidate herbicide and showed higher activity than the lead com-
pound II7. The results of the weed controlling spectrum tests
showed that 2h could effectively control dayflower, bur beg-
garticks, youth-and-old age, cassia tora, velvet leaf, purslane and
false daisy. In addition, the mixture of 2h and propanil shows a
synergistic effect and enhanced the herbicidal activity. The results
of the herbicidal activity assays in field tests in Liaoning demon-
strated that 2h could effectively control dayflower and nightshade
with long-lasting persistence. The activity of 2h at 30 g a.i./ha
showed higher activity than bentazon at 1440 g a.i./ha and com-
pound II7 at 30 g a.i./ha. Our results suggested that 2h could be a
novel candidate for a herbicide. This study will be useful for the
design of new herbicides for weed control.
5
.1.2. Synthesis of compounds 2a and 2h
The intermediate 1 (3 mmol) in 20 mL THF was added dropwise
to ethyl glycinate (3.6 mmol) and triethylamine (6 mmol) in 0–
°C, and then the mixture was stirred at room temperature. The
mixture was concentrated under reduced pressure to obtain Ethyl
(2-chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)phenyl)-
5
(
1
sulfonyl)glycinate (2a). Yield: 45%. Melting point: 93–95 °C.
NMR (300 MHz, CDCl ) d (ppm) = 8.86 (s, 1H), 8.51 (d, J = 2.2 Hz,
H), 8.07 (d, J = 1.9 Hz, 1H), 7.96 (dd, J = 8.3, 2.2 Hz, 1H), 7.65 (d,
J = 8.3 Hz, 1H), 5.76(s, 1H), 4.17 (s, 2H), 4.16–4.14 (m, 2H), 1.28–
.23 (m, 3H). Anal. Calcd for C16 S: C, 42.03; H, 2.87;
N, 6.13. Found: C, 40.03; H, 2.88; N, 6.14. HRMS: m/z 478.9923
H
3
H
1
1
2 3 2 4
H13Cl F N O
+
+
[
M+Na] (calcd [M+Na] : 478.9925).
The intermediate 1 (3 mmol) in 20 mL THF was added dropwise
to ethyl methylglycinate (3.6 mmol) and triethylamine (6 mmol) in
–5 °C, and then the mixture was stirred at room temperature. The
0
mixture was concentrated under reduced pressure to obtain Ethyl
N-((2-chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)phenyl)-
sulfonyl)-N-methylglycinate (2h). Yield: 50%. Melting point: 76–
1
7
8 °C. H NMR (300 MHz, CDCl
) d
3 H
(ppm) = 8.86 (s, 1H), 8.57 (d,
5
5
. Experiments
J = 2.2 Hz, 1H), 8.07 (d, J = 1.9 Hz, 1H), 7.92 (dd, J = 8.3, 2.2 Hz,
H), 7.65 (d, J = 8.3 Hz, 1H), 4.17 (s, 2H), 4.16–4.14 (m, 2H), 3.03
s, 3H), 1.28–1.23 (m, 3H). Anal. Calcd for C17 S: C,
3.33; H, 3.21; N, 5.94. Found: C, 43.34; H, 3.22; N, 5.95. HRMS:
1
(
4
.1. Chemistry
2 3 2 4
H15Cl F N O
All starting materials and reagents were commercially available
+
+
m/z 492.9982 [M+Na] (calcd [M+Na] : 492.9980).
and used without further purification except as indicated. Melting
points were determined on a Büchi melting point apparatus and
1
5.1.3. General procedure for preparation of compounds 2b–2g
and 2i–2u
are uncorrected. H NMR spectra were recorded with a Mercury
3
00 (Varian, 300 MHz) spectrometer with deuterochloroform as
To a solution of compounds 2a or 2h (10 mmol) in THF (30 mL)
were added NaOH (20 mmol) aqueous solution (30 mL). The reac-
tion mixture was stirred at room temperature for 6 h, then pH
value of the mixture was adjusted to 2 using hydrochloric acid
and the mixture was concentrated under reduced pressure to
obtain a crude solid. The crude solid and sulfoxide chloride
the solvent and tetramethylsilane (TMS) as the internal standard.
Elemental analyses were determined on a Yanaco MT-3CHN
elemental analyzer. Mass spectra were obtained on Agilent
Technologies 6230 TOF LC/MS.
An overview synthesis of substituted 3-(pyridin-2-yl)benzene-
sulfonamide derivatives 2 is shown in Scheme 1.
(
20 mmol) in toluene (50 mL) was refluxed for 4 h, after which
time the transparent solution has formed. The mixture was con-
centrated under reduced pressure to yield a yellow liquid. Lastly,
the yellow liquid, the corresponding alcohols or amines (10 mmol)
and triethylamine (20 mmol) in anhydrous THF (25 mL) were stir-
red at the room temperature for 2 h. The mixture was concentrated
under reduced pressure. Then the crude product was purified by
column chromatography with a mixture of ethyl acetate and petro-
leum ether (1:3) to yield target compounds 2b–2g and 2i–2u.
5
.1.1. Synthesis of 2-Chloro-5-(3-chloro-5-(trifluoromethyl)
pyridin-2-yl)benzenesulfonyl chloride (1)
.1.1.1. Synthesis of 3-chloro-2-(4-chlorophenyl)-5-(trifluo-
romethyl)pyridine. 2,3-dichloro-5-(trifluoromethyl)pyridine
0.18 mol), 4-chlorobezeneboronic (0.18 mol), tetrakis(triph-
enylphosphine)palladium(0) (0.61 mmol) and sodium bicarbonate
0.539 mol) in a mixture of 550 mL of dimethoxyethane and
50 mL of water were refluxed for four hours. The mixture was then
5
(
(
5
acidified to pH value 4–5 with dilute hydrochloric acid and
dimethoxyethane was removed by distillation. The remaining
5
.1.3.1. 2-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-
yl)phenyl)sulfonamido)-N-methylacetamide (2b). Yellow
(ppm) = 8.88 (s, 1H), 8.59 (s,
20,21
aqueous phase was extracted with methylene chloride.
The
1
3 H
liquid. H NMR (300 MHz, CDCl ) d
Please cite this article in press as: Xie, Y.; et al. Bioorg. Med. Chem. (2015), http://dx.doi.org/10.1016/j.bmc.2015.08.037

Y. Xie et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
5
1
5
O
H), 8.10 (s, 1H), 7.98 (d, J = 8.3 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H),
.19 (s, 2H), 3.61 (s, 2H), 2.81(s, 3H). Anal. Calcd for C15 F3N
S: C, 40.74; H, 2.74; N, 9.50. Found: C, 40.75; H, 2.74; N, 9.51.
1H), 4.13 (s, 2H), 3.02 (s, 3H), 2.03 (s, 1H), 1.21 (d, J = 6.3 Hz, 6H).
Anal. Calcd for C18 O4S: C, 44.55; H, 3.53; N, 5.77. Found:
H12Cl
2
3
-
2 3 2
H17Cl F N
+
3
C, 44.56; H, 3.54; N, 5.78. HRMS: m/z 507.0137 [M+Na] (calcd [M
+
+
+
HRMS: m/z 463.9826 [M+Na] (calcd [M+Na] : 4463.9827).
+Na] : 507.0136).
5
.1.3.2. 2-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-
yl)phenyl)sulfonamido)-N-ethylacetamide (2c). Yellow liq-
uid. 1H NMR (300 MHz, CDCl
) d (ppm) = 8.87 (s, 1H), 8.53 (d,
5.1.3.9. Butyl N-((2-chloro-5-(3-chloro-5-(trifluoromethyl)pyri-
din-2-yl)phenyl)sulfonyl)-N-methylglycinate (2k).
Yellow
1
3
H
liquid. H NMR (300 MHz, CDCl ) d (ppm) = 8.86 (s, 1H), 8.57
3 H
J = 2.1 Hz, 1H), 8.08 (s, 1H), 8.00 (dd, J = 8.3, 2.2 Hz, 1H), 7.69 (d,
J = 8.3 Hz, 1H), 6.15 (s, 1H), 5.80 (s, 1H), 3.61 (d, J = 6.1 Hz, 2H),
(d, J = 2.0 Hz, 1H), 8.08 (s, 1H), 7.92 (dd, J = 8.3, 2.1 Hz, 1H),
7.65 (d, J = 8.3 Hz, 1H), 4.18 (s, 2H), 4.11 (t, J = 6.6 Hz, 2H), 3.03
(s, 3H), 1.39–1.33 (m, 4H), 0.91 (t, J = 7.3 Hz, 3H). Anal. Calcd
3
.32 (d, J = 7.3 Hz, 2H), 1.12 (t, J = 7.3 Hz, 3H). Anal. Calcd for C16
-
H
14Cl
2
F
3
N
3
O
3
S: C, 42.12; H, 3.09; N, 9.21. Found: C, 42.13; H,
2 3 2 4
for C19H19Cl F N O S: C, 45.70; H, 3.84; N, 5.61 Found: C,
+
+
+
3
.09; N, 9.23. HRMS: m/z 477.9883 [M+Na] (calcd [M+Na] :
45.71; H, 3.85; N, 5.63. HRMS: m/z 521.0292 [M+Na] (calcd [M
+
4
77.9883).
+Na] : 521.0293).
5
.1.3.3. 2-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-
5.1.3.10. 2-Methoxyethyl N-((2-chloro-5-(3-chloro-5-(trifluo-
yl)phenyl)sulfonamido)-N,N-dimethylacetamide (2d).
Yel-
low solid. Melting point: 170–172 °C. H NMR (300 MHz, CDCl
(ppm) = 8.88 (s, 1H), 8.59 (s, 1H), 8.10 (s, 1H), 7.98 (d,
J = 8.3 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 5.19 (s, 2H), 3.61 (s, 2H),
.57 (s, 6H). Anal. Calcd for C16 S: C, 42.12; H, 3.09;
N, 9.21. Found: C, 42.12; H, 3.08; N, 9.20. HRMS: m/z 477.9982
romethyl)pyridin-2-yl)phenyl)sulfonyl)-N-methylglycinate
1
1
3
)
(2l).
Yellow liquid. H NMR (300 MHz, CDCl
) d
3 H
(ppm)
d
H
= 8.87 (s, 1H), 8.58 (d, J = 2.2 Hz, 1H), 8.08 (s, 1H), 7.93 (dd,
J = 8.3, 2.2 Hz, 1H), 7.66 (d, J = 8.3 Hz, 1H), 4.31–4.21 (m, 4H),
3.59 (dd, J = 5.4, 3.9 Hz, 2H), 3.38 (s, 3H), 3.03 (s, 3H). Anal. Calcd
1
2 3 3 3
H14Cl F N O
for C18
H, 3.41; N, 5.58. HRMS: m/z 523.0085 [M+Na] (calcd [M+Na] :
23.0085).
2 3 2 5
H17Cl F N O S: C, 43.13; H, 3.42; N, 5.59. Found: C, 43.12;
+
+
+
+
[
M+Na] (calcd [M+Na] : 477.9983).
5
5
.1.3.4. 2-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-
yl)phenyl)sulfonamido)-N,N-diethylacetamide (2e). Yellow
(ppm) = 8.88 (s, 1H), 8.59 (s,
H), 8.10 (s, 1H), 7.98 (d, J = 8.3 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H),
.34 (s, 1H), 5.33 (s, 2H), 3.86 (d, J = 4.3 Hz, 2H), 3.43–3.31 (m,
H), 1.24–0.82 (m, 6H). Anal. Calcd for C18 S: C,
4.64; H, 3.75; N, 8.68. Found: C, 44.64; H, 3.76; N, 8.68. HRMS:
5.1.3.11. 2-Ethoxyethyl N-((2-chloro-5-(3-chloro-5-(trifluo-
1
liquid. H NMR (300 MHz, CDCl
) d
3 H
romethyl)pyridin-2-yl)phenyl)sulfonyl)-N-methylglycinate
1
1
6
2
4
(2m).
(300 MHz, CDCl
Yellow solid. Melting point: 78–80 °C.
) d
H NMR
3
H
(ppm) = 8.86 (s, 1H), 8.57 (d, J = 2.2 Hz,
H18Cl
2
F
3
3
N O
3
1H), 8.08 (s, 1H), 7.93 (dd, J = 8.3, 2.2 Hz, 1H), 7.65 (d,
J = 8.3 Hz, 1H), 4.38–4.11 (m, 4H), 3.72–3.58 (m, 2H), 3.52 (q,
J = 7.0 Hz, 2H), 3.02 (s, 3H), 1.21 (t, J = 7.0 Hz, 3H). Anal. Calcd
+
+
m/z 506.0298 [M+Na] (calcd [M+Na] : 506.0296).
2 3 2 5
for C19H19Cl F N O S: C, 44.28; H, 3.72; N, 5.44. Found: C,
+
5
.1.3.5. 2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-
44.29; H, 3.73; N, 5.46. HRMS: m/z 537.0241 [M+Na] (calcd [M
+Na] : 537.0242).
+
N-(2-morpholino-2-oxoethyl)benzenesulfonamide
1
(
2f).
s, 1H), 8.53 (d, J = 2.1 Hz, 1H), 8.10 (s, 1H), 7.98 (dd, J = 8.3, 2.2 Hz,
H), 7.70 (d, J = 8.3 Hz, 1H), 5.32 (s, 1H), 3.82–3.67 (m, 4H), 3.61 (d,
J = 6.1 Hz, 2H), 3.42–3.27 (m, 4H). Anal. Calcd for C18
S: C, 43.39; H, 3.24; N, 8.43. Found: C, 43.40; H, 3.25; N, 8.42.
3 H
Yellow liquid. H NMR (300 MHz, CDCl ) d (ppm) = 8.89
(
1
5.1.3.12.
But-3-yn-1-yl
N-((2-chloro-5-(3-chloro-5-(trifluo-
romethyl)pyridin-2-yl)phenyl)sulfonyl)-N-methylglycinate
1
H16Cl
2
F
3
N
O
3 4
-
(2n).
(300 MHz, CDCl
8.08 (s, 1H), 7.93 (dd, J = 8.3, 2.2 Hz, 1H), 7.66 (d, J = 8.3 Hz, 1H),
.30 (s, 1H), 4.71 (d, J = 2.4 Hz, 2H), 4.25 (s, 2H), 3.04 (s, 3H), 2.49
Yellow solid. Melting point: 76–78 °C.
H NMR
3
) d (ppm) = 8.86 (s, 1H), 8.56 (d, J = 2.2 Hz, 1H),
H
+
+
HRMS: m/z 520.0089 [M+Na] (calcd [M+Na] : 520.0089).
5
5
.1.3.6. N-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-
yl)phenyl)sulfonyl)-N-methylglycine (2g). Yellow solid.
Melting point: 176–178 °C. H NMR (300 MHz, CDCl ) d (ppm)
8.87 (s, 1H), 8.58 (d, J = 2.1 Hz, 1H), 8.09 (s, 1H), 7.95 (dd,
J = 8.3, 2.2 Hz, 1H), 7.67 (d, J = 8.3 Hz, 1H), 4.34 (s, 2H), 3.03 (s,
H). Anal. Calcd for C15 S: C, 40.65; H, 2.50; N, 6.32.
Found: C, 40.65; H, 2.48; N, 6.33. HRMS: m/z 464.9666 [M+Na]
(t, J = 2.4 Hz, 2H). Anal. Calcd for C19H15Cl2F3N2O4S: C, 46.08;
H, 3.05; N, 5.66. Found: C, 46.09; H, 3.06; N, 5.68. 516.9977 [M
1
+
+
3
H
+Na] (calcd [M+Na] : 516.9980).
=
5.1.3.13.
(Tetrahydrofuran-2-yl)methyl
N-((2-chloro-5-
3
2 3 2 4
H11Cl F N O
(3-chloro-5-(trifluoromethyl)pyridin-2-yl)phenyl)sulfonyl)-N-
+
1
methylglycinate (2o).
CDCl ) d (ppm) = 8.86 (d, J = 1.0 Hz, 1H), 8.56 (d, J = 2.1 Hz, 1H),
.07 (d, J = 1.3 Hz, 1H), 7.92 (dd, J = 8.3, 2.2 Hz, 1H), 7.65 (d,
Yellow liquid. H NMR (300 MHz,
+
(
calcd [M+Na] : 464.9667).
3
H
8
5
.1.3.7. 2,2,2-Trifluoroethyl N-((2-chloro-5-(3-chloro-5-(trifluo-
J = 8.3 Hz, 1H), 5.30 (s, 1H), 4.22 (d, J = 9.0 Hz, 2H), 4.13–3.98 (m,
romethyl)pyridin-2-yl)phenyl)sulfonyl)-N-methylglycinate
2H), 3.92–3.71 (m, 2H), 3.02 (s, 3H), 1.99–1.81 (m, 4H). Anal. Calcd
1
(
(
1
2i).
300 MHz, CDCl
H), 8.09 (s, 1H), 7.95 (dd, J = 8.3, 2.2 Hz, 1H), 7.67 (d,
J = 8.3 Hz, 1H), 4.52 (q, J = 8.3 H, 2H), 4.33 (s, 2H), 3.03 (s, 3H).
Anal. Calcd for C17 S: C, 38.87; H, 2.30; N, 5.33.
Found: C, 38.88; H, 2.30; N, 5.33. HRMS: m/z 546.9695 [M+Na]
Yellow solid. Melting point: 78–80 °C.
H
NMR
19 l2 3 2 5
for C20H C F N O S: C, 45.55; H, 3.63; N, 5.31. Found: C, 45.56; H,
+
+
3
) d (ppm) = 8.87 (s, 1H), 8.58 (d, J = 2.1 Hz,
H
3.63; N, 5.31. HRMS: m/z 549.0245 [M+Na] (calcd [M+Na] :
549.0242).
H12Cl
F
2 6
N
2
O
4
5.1.3.14. 2-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-
+
yl)-N-methylphenyl)sulfonamido)-N-methylacetamide
+
Yellow solid. Melting point: 116–118 °C. 1H NMR
(
calcd [M+Na] : 546.9697).
(2p).
3 H
300 MHz, CDCl ) d (ppm) = 8.86 (s, 1H), 8.53 (d, J = 2.0 Hz, 1H),
(
5
.1.3.8. Isopropyl N-((2-chloro-5-(3-chloro-5-(trifluoromethyl)
8.08 (s, 1H), 7.98 (dd, J = 8.3, 2.0 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H),
6.55 (s, 1H), 3.93 (s, 2H), 2.97 (s, 3H), 2.86 (t, J = 6.0 Hz, 3H). Anal.
pyridin-2-yl)phenyl)sulfonyl)-N-methylglycinate (2j).
low solid. Melting point: 66–68 °C. H NMR (300 MHz, CDCl
Yel-
) d
1
3
H
1 2 3 3 3
Calcd for C16H 4Cl F N O S: C, 42.12; H, 3.09; N, 9.21. Found: C,
+
(
ppm) = 8.91–8.78 (m, 1H), 8.56 (d, J = 2.2 Hz, 1H), 8.06 (d,
42.13; H, 3.08; N, 9.23. HRMS: m/z 477.9981 [M+Na] (calcd [M
+
J = 2.0 Hz, 1H), 7.91 (dd, J = 8.3, 2.2 Hz, 1H), 7.64 (d, J = 8.3 Hz,
+Na] : 477.9983).
Please cite this article in press as: Xie, Y.; et al. Bioorg. Med. Chem. (2015), http://dx.doi.org/10.1016/j.bmc.2015.08.037

6
Y. Xie et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
5
.1.3.15. 2-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-
The plants were kept at 10–25 °C, or 20–35 °C depending on the
species. The test lasted 2 to 4 weeks during which time the plants
were tended and their reaction to the individual treatments was
evaluated.
Evaluation was on a scale from 0 to 100, where 100 means no
emergence of the plants or complete destruction of at least the
above-ground parts and 0 means no damage or normal growth.
The plants used in the greenhouse tests comprised the follow-
ing species: velvet leaf (Abutilon theophrasti medic.), youth-and-
old age (Zinnia elegans jacq.), barnyard grass (Echinochloa crus-galli
(L.) beauv.) and foxtail (Setaria glauca (L.) beauv.).
yl)-N-methylphenyl)sulfonamido)-N,N-diethylacetamide
1
(
(
8
4
2q).
300 MHz, CDCl
Yellow solid. Melting point: 80–82 °C.
) d (ppm) = 8.85 (s, 1H), 8.56 (d, J = 2.2 Hz, 1H),
.06 (s, 1H), 7.91 (dd, J = 8.3, 2.2 Hz, 1H), 7.64 (d, J = 8.3 Hz, 1H),
.22 (s, 2H), 3.33 (q, J = 7.2 Hz, 4H), 3.03 (s, 3H), 1.23 (dd,
H
NMR
3
H
J = 12.8, 5.7 Hz, 3H), 1.08 (t, J = 7.1 Hz, 3H). Anal. Calcd for C19
Cl S: C, 45.79; H, 4.05; N, 8.43. Found: C, 45.79; H, 4.06; N,
20
H -
2 3 3 3
F N O
+
+
8
.44. HRMS: m/z 520.0453 [M+Na] (calcd [M+Na] : 520.0453).
5
.1.3.16. 2-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-
yl)-N-methylphenyl)sulfonamido)-N-cyclopropylacetamide
1
(
(
8
6
(
2r).
Yellow solid. Melting point: 91–93 °C.
) d (ppm) = 8.87 (s, 1H), 8.53 (d, J = 2.2 Hz, 1H),
.09 (s, 1H), 7.99 (dd, J = 8.3, 2.2 Hz, 1H), 7.69 (d, J = 8.3 Hz, 1H),
.56 (s, 1H), 3.89 (s, 2H), 2.97 (s, 3H), 2.33–2.10 (m, 1H), 0.82
S: C,
4.83; H, 3.34; N, 8.71. Found: C, 44.82; H, 3.34; N, 8.70. HRMS:
H
NMR
5.2.2. The weed controlling spectrum test of 2h
300 MHz, CDCl
3
H
The weed controlling spectrum test was performed using the
same method as for herbicidal activity assay in greenhouse tests.
The plants used in the weed controlling spectrum tests comprised
the following species: barnyard grass (Echinochloa crus-galli (L.)
beauv.), foxtail (Setaria glauca (L.) beauv.), velvet leaf (Abutilon theo-
phrasti medic.), youth-and-old age (Zinnia elegans jacq.), crabgrass
2 3 3 3
dd, J = 12.7, 7.1 Hz, 4H). Anal. Calcd for C18H16Cl F N O
4
+
+
m/z 504.0140 [M+Na] (calcd [M+Na] : 504.0140).
(Digitaria sanguinalis), dayflower (Commelina tuberosa), bur beg-
5
.1.3.17. 2-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-
garticks (Bidens tripartita linn.), cassia tora (Cassiaobtusifolia L.),
purslane (Portulaca oleracea) and false daisy (Eclipta prostrate L.).
yl)-N-methylphenyl)sulfonamido)-N-phenylacetamide
(
(
8
2s).
300 MHz, CDCl
.30 (s, 1H), 8.11 (s, 1H), 8.03 (dd, J = 8.3, 2.2 Hz, 1H), 7.74 (d,
J = 8.3 Hz, 1H), 7.58 (d, J = 7.6 Hz, 2H), 7.37 (t, J = 7.9 Hz, 2H), 7.17
t, J = 7.4 Hz, 1H), 4.05 (s, 2H), 3.10 (s, 3H). Anal. Calcd for C21
Cl S: C, 48.66; H, 3.11; N, 8.11. Found: C, 48.66; H, 3.12; N,
Yellow solid. Melting point: 176–178 °C. 1H NMR
) d (ppm) = 8.89 (s, 1H), 8.61 (d, J = 2.1 Hz, 1H),
3
H
5.2.3. Herbicidal activity of 2h combined with propanil
The experiment was performed using the same method as for
herbicidal activity assays in greenhouse tests. The plants used in
the weed controlling spectrum tests comprised the following spe-
cies: barnyard grass (Echinochloa crus-galli (L.) beauv.), foxtail
(Setaria glauca (L.) beauv.), crabgrass (Digitaria sanguinalis), velvet
leaf (Abutilon theophrasti medic.), dayflower (Commelina tuberosa),
false daisy (Eclipta prostrate L.) and rice.
(
16
H -
2 3 3 3
F N O
+
+
8
.12. HRMS: m/z 540.0139 [M+Na] (calcd [M+Na] : 540.0140).
5
.1.3.18. 2-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-2-
yl)-N-methylphenyl)sulfonamido)-N-(4-chlorophenyl)acetamide
1
(
(
1
7
2t).
Yellow solid. Melting point: 180–182 °C.
) d (ppm) = 8.87 (s, 1H), 8.58 (s, 1H), 8.33 (s,
H), 8.09 (s, 1H), 8.02 (d, J = 8.3 Hz, 1H), 7.72 (d, J = 8.3 Hz, 1H),
.52 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.7 Hz, 2H), 4.02 (s, 2H), 3.08
F3N S: C, 45.63; H, 2.74; N,
.60. Found: C, 45.63; H, 2.75; N, 7.61. HRMS: m/z 573.9750 [M
H
NMR
5.2.4. Herbicidal activity assay of 2h in field tests
300 MHz, CDCl
3
H
The experiment of the field tests was performed on the basis of
field efficacy trials of Chinese pesticide standards (a) GB/
T17980.40-2000. The test weeds in rice field were at the 2–4 leaf
stage. The spray volume was 450 L/ha by foliar application, then
after 24–48 h treated, the water depth should be kept at 3–5 cm
for 5–7 days, but do not make the water flooded rice leaves. Ran-
domised completed block with 2 replicates. Every treated area
(
s, 3H). Anal. Calcd for C21
H15Cl
3
3 3
O
7
+
+
+
Na] (calcd [M+Na] : 573.9750).
2
5
2
.1.3.19. 2-((2-Chloro-5-(3-chloro-5-(trifluoromethyl)pyridin-
-yl)-N-methylphenyl)sulfonamido)-N-(2-chloropyridin-3-yl)-
and untreated area was 20 m . Density of unwanted weeds is
2
80–150 plants/m in the untreated area. The controlled weeds
1
acetamide (2u).
NMR (300 MHz, CDCl
(
1
Yellow solid. Melting point: 152–154 °C.
) d
H
comprised the following species: dayflower (Commelina tuberosa)
and nightshade (disambiguation) in Liaoning. The application rate
for treatment was 30 and 60 g a.i./ha. The application rate for treat-
ment of Bentazon (48%, water dispersible granule) which was used
as the control in Liaoning was 1440 g a.i./ha.
Formulas used in this tests as follows: Control effect (%) = (the
number of live weeds in the control area À the number of live
weeds in the treated area)/the number of live weeds in the control
area  100%.
3
H
(ppm) = 8.87 (s, 1H), 8.80 (s, 1H), 8.69
dd, J = 8.2, 1.7 Hz, 1H), 8.61 (d, J = 2.1 Hz, 1H), 8.16 (dd, J = 4.7,
.7 Hz, 1H), 8.09 (s, 1H), 8.02 (dd, J = 8.3, 2.2 Hz, 1H), 7.72 (d,
J = 8.3 Hz, 1H), 7.32–7.27 (m, 1H), 4.17 (s, 2H), 3.09 (s, 3H). Anal.
Calcd for C20 S: C, 43.38; H, 2.55; N, 10.12. Found: C,
3.39; H, 2.56; N, 10.12. HRMS: m/z 574.9702 [M+Na] (calcd [M
H
14Cl
3
F
3
N
4
O
3
+
4
+
+
Na] : 574.9702).
5
5
.2. Herbicidal activity assay
Acknowledgment
.2.1. Herbicidal activity assay in greenhouse tests
All plant materials were obtained from the Agrochemical Dis-
We thank prof. Stephen S. Tobe for assistance with manuscript
preparation.
covery Department in Shenyang Research Institute of Chemical
Industry. Plants were grown in plastic flowerpots containing loamy
sand with about 3.0% humus as substrate. The seeds of the test
plants were sown separately according to species.
References and notes
The test plants were grown to a height of 3–15 cm, depending
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were germinated separately and transplanted into the test vessels
a few days before the treatment. The application rate for post-
emergence treatment were 600, 150 and 37.5 g a.i./ha.
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