Controllable Effect of Structural Modification of Sulfonylurea Herbicides on Soil Degradation

Article abstract of DOI:10.1002/cjoc.201600438

The study of soil degradation behaviors of sulfonylurea herbicides in relation to their different structural attributes is utmost important for us to comprehend the development of new eco-friendly herbicides. It is postulated that the structural modification of the chemical structures could influence their degradation rates in soil. Nine devised structures were synthesized to study their herbicidal activity as well as their soil degradation behaviors respectively. The novel compounds I-3–I-7 were characterized by UV,¹H NMR and¹³C NMR, MS and EA. Bioassays indicated that most of target compounds displayed superior herbicidal activities in comparison with Chlorsulfuron. Soil degradation results further confirmed our previous assumption that the introduction of electron-donating substituents at 5^thposition of the benzene ring distinctly increased their degradation rates, among which dimethylamino and diethylamino groups can adjust the degradation rate to a more favorable status.

Full text of DOI:10.1002/cjoc.201600438

FULL PAPER
DOI: 10.1002/cjoc.201600438
Controllable Effect of Structural Modification of
Sulfonylurea Herbicides on Soil Degradation
Xuewen Hua, Shaa Zhou, Minggui Chen, Wei Wei, Ming Liu, Kang Lei, Sha Zhou,
Yonghong Li, Baolei Wang, and Zhengming Li*
State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science
and Engineering (Tianjin), Nankai University, Tianjin 300071, China
The study of soil degradation behaviors of sulfonylurea herbicides in relation to their different structural attrib-
utes is utmost important for us to comprehend the development of new eco-friendly herbicides. It is postulated that
the structural modification of the chemical structures could influence their degradation rates in soil. Nine devised
structures were synthesized to study their herbicidal activity as well as their soil degradation behaviors respectively.
The novel compounds I-3－I-7 were characterized by UV, 1H NMR and 13C NMR, MS and EA. Bioassays indicat-
ed that most of target compounds displayed superior herbicidal activities in comparison with Chlorsulfuron. Soil
degradation results further confirmed our previous assumption that the introduction of electron-donating substitu-
ents at 5th position of the benzene ring distinctly increased their degradation rates, among which dimethylamino and
diethylamino groups can adjust the degradation rate to a more favorable status.
Keywords sulfonylurea herbicides, synthesis, herbicidal activity, soil degradation
Introduction
prohibited in China (Figure 1), which somewhat limited
the development of some of these hyper-active herbi-
cides.
The environmental fate of agrochemicals in soil is
viewed with great concern today, due to their toxicity or
potential adverse influence on ecosystems.[1] The rate of
mobility and degradation in soil are the most important
factors that determine the fate of agrochemicals in soil.[2]
Therefore, degradation studies in soils are essential for
the evaluation of persistence of agrochemicals in eco-
logical environment. The systemic study of relationship
about soil degradation behaviors and structural modifi-
cation is considered to be utmost important which has
not been reported before. It will contribute to further
development of environment-friendly agrochemicals
and to greatly decrease the residual problems involved.
Due to their specific role in plant acetohydroxyacid
synthase (AHAS),[3,4] sulfonylurea herbicides have the
advantages of super-high herbicidal activity, ultra-low
application rate, high selectivity, low toxicity, etc.[5,6]
During the past three decades, these herbicides have
been widely used to control annual or perennial broad-
leaf and grass weeds.[7,8] Along with the large-scale ap-
plication of these herbicides, however, some of them
have exhibited some problems, such as residual phyto-
toxicity and weed resistance, which have caused serious
economic losses under the particular multi-crop rotation
planting pattern in China.[9-11] In 2013, Chlorsulfuron,
Metsulfuron-methyl and Ethametsulfuron have been
Figure 1 Structures of the prohibited sulfonylurea herbicides in
China.
In our previous work, we reported the tri-factor rela-
tionship of structural modification/herbicidal activi-
ty/soil degradation of Chlorsulfuron in a hitherto un-
precedented approach. It was concluded that the intro-
duction of various substituents at 5th position of the
benzene ring in Chlorsulfuron can remain or vary the
herbicidal activities of revised structures, on the other
*
E-mail: nkzml@vip.163.com; Tel.: 0086-022-23503732; Fax: 0086-022-23503732
Received July 18, 2016; accepted August 22, 2016; published online XXXX, 2016.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201600438 or from the author.
Chin. J. Chem. 2016, XX, 1—8
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1

Hua et al.
FULL PAPER
hand, can influence the soil degradation rates where
electron-donating groups are favorable, especially di-
methylamino group (Figure 2).[12] Based on these find-
ings, our continuing interest in controllable degradation
of sulfonylurea herbicides directed us to further intro-
duce other substituents at 5th position of the benzene
ring in order to validate the obtained degradation rules
and to explore the influence of different substituted
amino groups on soil degradation rates. Therefore,
compounds I-1－I-9 (Figure 2) were employed to as-
sess their herbicidal activity and soil degradation rates,
in which products I-1, I-2, I-8 and I-9 were obtained
within our laboratory,[12,13] while others (I-3－I-7) were
synthesized according to the methods in Scheme 1
where the corresponding intermediates II were prepared
using the procedures in Scheme 2.
using silica gel (200－300 mesh). The test soil from the
plain of Ji’an city (Jiangxi Province, China) was sam-
pled from the upper layer (0－25 cm), air-dried in the
shade and passed through a 2 mm sieve.
General synthetic procedure for intermediates III-3,
III-4 and III-7
Ethyl-(2-chloro-5-acetamidophenylsulfonyl) carba-
mate (III-3) was synthesized as follows.[14] To a solu-
tion of 2-chloro-5-acetamidophenylsulfonyl (II-3) (1.60
g, 6.4 mmol), potassium carbonate (1.78 g, 12.9 mmol)
in acetone (30 mL) was added ethyl chloroformate (0.84
g, 7.7 mmol). The mixture was refluxed for 8 h, and the
progress was monitored by TLC. After completion of
the reaction, acetone was removed by concentration in
vacuum, and the residue was dissolved in water/ethyl
acetate (V/V 20/20). The water layer was separated
through extraction and then acidified to pH 4.0 with
diluted hydrochloric acid. The resulting precipitate was
obtained by filtration, and applied directly to the next
step reaction after drying. Intermediates III-4 and III-7
were prepared similarly.
CH3
Cl
N
N
SO2NHCONH
N
OCH3
R
Ethyl-(2-chloro-5-acetamidophenylsulfonyl) car-
bamate (III-3) White granules, yield 97%, m.p. 148
－150 ℃; H NMR (DMSO-d6, 400 MHz) δ: 12.49 (s,
Previous work
1
R = H (Chlorsulfuron), CH3, C2H5, i-C3H7,
1H, SO2NH), 10.44 (s, 1H, CONH), 8.37 (d, J＝2.6 Hz,
1H, Ph-H), 7.95 (dd, J＝8.7, 2.6 Hz, 1H, Ph-H), 7.61 (d,
J ＝ 8.7 Hz, 1H, Ph-H), 4.02 (d, J ＝ 7.1 Hz, 2H,
CH2CH3), 2.09 (s, 3H, COCH3), 1.09 (t, J＝7.1 Hz, 3H,
CH2CH3).
N(CH3)2, NO2, F, Cl, Br, I, CN, CF3
Present work
R = H (Chlorsulfuron, I-1), N(CH3)2 (I-2), NHCOCH3
(I-3), OCH3 (I-4), NH2 (I-5), NHSO2CH3 (I-6), N(C2H5)2
(I-7), CH=CH2 (I-8), CH=N-OCH3 (I-9)
Ethyl-(2-chloro-5-methoxyphenylsulfonyl)
car-
bamate (III-4) White granules, yield 92%, m.p. 134
1
－136 ℃; H NMR (DMSO-d6, 400 MHz) δ: 12.51 (s,
Figure 2 Structures of Chlorsulfuron derivatives in previous
and present work.
1H, NH), 7.60 (d, J＝8.8 Hz, 1H, Ph-H), 7.53 (d, J＝3.1
Hz, 1H, Ph-H), 7.29 (dd, J＝8.8, 3.1 Hz, 1H, Ph-H),
4.02 (q, J＝7.1 Hz, 2H, CH2CH3), 3.84 (s, 3H, OCH3),
1.08 (t, J＝7.1 Hz, 3H, CH2CH3).
Experimental
Ethyl-(2-chloro-5-diethylaminophenylsulfonyl)
carbamate (III-7) Transparent granules, yield 92%,
m.p. 126－128 ℃; H NMR (d6-DMSO, 400 MHz) δ:
12.27 (s, 1H, NH), 7.36 (d, J＝8.9 Hz, 1H, Ph-H), 7.24
(d, J＝3.2 Hz, 1H, Ph-H), 6.91 (dd, J＝9.0, 3.2 Hz, 1H,
Ph-H), 4.02 (q, J＝7.1 Hz, 2H, OCH2CH3), 3.41－3.35
(m, 4H), 1.12－1.07 (m, 9H).
Materials and instruments
1
All reaction reagents were analytical grade, while all
analytical reagents for high performance liquid chro-
matograph (HPLC) were HPLC grade, including meth-
anol, acetonitrile, etc. Melting points of all compounds
were determined on an X-4 binocular microscope
(Gongyi Tech. Instrument Co., Henan, China), and the
temperatures were uncorrected. 1H and 13C nuclear
magnetic resonance (NMR) spectra were obtained on a
Bruker AV-400 spectrometer (400 MHz), and chemi-
cal-shift values (δ) were reported as parts per million
with tetramethylsilane as the internal standard. Ele-
mental analyses (EA) were measured on a vario EL
CUBE recorder. Ultraviolet (UV) spectra were per-
formed on a TU-1810 ultraviolet-visible spectropho-
tometer. Mass spectra were recorded on a Thermo-
Finnigan LCQ-Advantage LC/mass detector instrument.
HPLC data were obtained on a SHIMADZU LC-20AT.
Column chromatography purification was carried out
General synthetic procedure for target compounds
I-3, I-4 and I-7
1-(2-Chloro-5-acetamidophenylsulfonyl)-3-(4-meth-
oxy-6-methyl-1,3,5-triazin-2-yl)urea (I-3) was synthe-
sized as previously described.[14] A solution of interme-
diate III-3 (0.94 g, 2.9 mmol), 4-methoxy-6-methyl-
1,3,5-triazin-2-amine (0.41 g, 2.9 mmol) in toluene (50
mL) was refluxed for 24 h, followed by concentration in
vacuum. The residue was purified by chromatography
on silica gel using petroleum ether/ethyl acetate (V/V＝
3∶1) as eluent to give white solid I-3. Products I-4 and
I-7 were prepared in a similar manner.
2
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Chin. J. Chem. 2016, XX, 1—8

Controllable Effect of Structural Modification of Sulfonylurea Herbicides on Soil Degradation
Scheme 1 Synthesis of the target compounds I-3－I-7
Scheme 2 Synthesis of intermediates II
Cl
Cl
Cl
Cl
Cl
NaNO2/HCl/
CH3COOH
NH2
SO2Cl
SO2NH2
SO2NH2
SO2NH2
.
.
25% - 28% NH3 H2O
(CH3CO)2O
Fe/HCl
CH2Cl2
r.t.
SO2/CuCl/
CuCl2/CH3COOH
NO2
NO2
NO2
NH2
NHCOCH3
4
1
2
3
II-3
Cl
Cl
Cl
Cl
SO2Cl
NO2
SO2NH2
NH2
.
25% - 28% NH3 H2O
Na2S2O4
NaNO2/HCl/CH3COOH
THF/H2O
r.t.
SO2/CuCl/CuCl2/CH3COOH
OCH3
OCH3
OCH3
OCH3
5
6
7
II-4
Cl
Cl
O
NaBH3CN
SO2NH2
SO2N
C N
40% CH3CHO
NaBH3CN, 40% CH3CHO
CH3COOH, CH3CN, 50 °C
DMF-DMA
CH2Cl2, r.t.
H
4
O
CH3COOH
CH3CN, r.t.
NHC2H5
NHC2H5
8
9
Cl
O
O
Cl
SO2N
C N
SO2NH2
.
H
NH2NH2 H2O
C2H5OH
N(C2H5)2
10
N(C2H5)2
II-7
1-(2-Chloro-5-acetamidophenylsulfonyl)-3-(4-
methoxy-6-methyl-1,3,5-triazin-2-yl)urea (I-3)
55.7, 25.6, 24.5; UV-vis (CH2Cl2) λmax: 232 nm; m/z
(ESI) [MH] calcd for C14H14ClN6O5S: 413.0, found
413.0. Anal. calcd for C14H15ClN6O5S: C 40.54, H 3.64,
N 20.26; found C 40.83, H 3.65, N 20.12.
White granules, yield 61%, m.p. 195－197 ℃; 1H
NMR (DMSO-d6, 400 MHz) δ: 12.85 (s, 1H, SO2NH),
11.07 (s, 1H, NHCOCH3), 10.48 (s, 1H, NHCONH),
8.41 (d, J＝2.4 Hz, 1H, Ph-H), 7.98 (dd, J＝8.7, 2.4 Hz,
1H, Ph-H), 7.63 (d, J＝8.7 Hz, 1H, Ph-H), 3.98 (s, 3H,
Ar-OCH3), 2.46 (s, 3H, Ar-CH3), 2.09 (s, 3H, COCH3);
13C NMR (DMSO-d6, 101 MHz) δ: 178.8, 170.6, 169.5,
164.3, 148.6, 139.1, 136.3, 132.7, 125.2, 123.8, 122.4,
1-(2-Chloro-5-methoxyphenylsulfonyl)-3-(4-
methoxy-6-methyl-1,3,5-triazin-2-yl)urea
(I-4)
White granules, yield 68%, m.p. 165－167 ℃; 1H
NMR (acetone-d6, 400 MHz) δ: 12.98 (s, 1H, SO2NH),
9.80 (s, 1H, NHCONH), 7.74 (d, J＝3.1 Hz, 1H, Ph-H),
7.57 (d, J＝8.8 Hz, 1H, Ph-H), 7.30 (dd, J＝8.8, 3.1 Hz,
Chin. J. Chem. 2016, XX, 1—8
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Hua et al.
FULL PAPER
1H, Ph-H), 4.05 (s, 3H, Ar-OCH3), 3.94 (s, 3H,
Ph-OCH3), 2.53 (s, 3H, Ar-CH3); 13C NMR (acetone-d6,
101 MHz) δ: 178.8, 170.8, 164.2, 158.4, 148.1, 137.1,
132.7, 122.1, 120.5, 117.9, 55.7, 54.9, 24.6; UV-vis
(CH2Cl2) λmax: 234 nm; m/z (ESI) [MH] calcd for
C13H13ClN5O5S: 386.0, found 385.9. Anal. calcd for
C13H14ClN5O5S: C 40.26, H 3.64, N 18.06; found C
40.52, H 3.59, N 18.29.
1-(2-Chloro-5-methanesulfonamidophenylsulf-
onyl)-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)urea
(I-6) White granules, yield 78%, m.p. 186－188 ℃;
1H NMR (DMSO-d6, 400 MHz) δ: 12.90 (s, 1H,
Ph-SO2NH), 11.11 (s, 1H, CH3SO2NH), 10.40 (s, 1H,
NHCONH), 8.02 (d, J＝2.7 Hz, 1H, Ph-H), 7.69 (d, J＝
8.7 Hz, 1H, Ph-H), 7.53 (dd, J＝8.7, 2.7 Hz, 1H, Ph-H),
3.98 (s, 3H, Ar-OCH3), 3.10 (s, 3H, SO2CH3), 2.46 (s,
3H, Ar-CH3); 13C NMR (d6-DMSO, 101 MHz) δ: 178.3,
170.0, 163.8, 148.2, 137.9, 136.3, 132.9, 125.0, 124.4,
122.1, 55.3, 25.1; UV-vis (CH2Cl2) λmax: 235 nm. m/z
1-(2-Chloro-5-diethylaminophenylsulfonyl)-3-(4-
methoxy-6-methyl-1,3,5-triazin-2-yl)urea
(I-7)
White granules, yield 63%, m.p. 174－176 ℃; 1H
NMR (acetone-d6, 400 MHz) δ: 12.84 (s, 1H, SO2NH),
9.72 (s, 1H, NHCONH), 7.48 (d, J＝3.2 Hz, 1H, Ph-H),
7.33 (d, J＝8.9 Hz, 1H, Ph-H), 6.95 (dd, J＝8.9, 3.2 Hz,
1H, Ph-H), 4.03 (s, 3H, Ar-OCH3), 3.47 (q, J＝7.0 Hz,
4H, CH2CH3), 2.51 (s, 3H, Ar-CH3), 1.19 (t, J＝7.0 Hz,
6H, CH2CH3); 13C NMR (acetone-d6, 101 MHz) δ:
179.8, 171.7, 165.2, 149.0, 147.3, 137.4, 133.1, 117.8,
116.0, 115.7, 55.9, 45.3, 25.5, 12.5; UV-vis (CH2Cl2)
λmax: 237 nm. m/z (ESI) [MH] calcd for C16H20Cl-
N6O4S: 427.1, found 427.0. Anal. calcd for C16H21Cl-
N6O4S: C 44.81, H 4.94, N 19.59; found C 44.83, H
4.86, N 19.52.

(ESI) [MH] calcd for C13H14ClN6O6S2 : 449.0, found
448.9. Anal. calcd for C13H15ClN6O6S2: C 34.63, H 3.35,
N 18.64; found C 34.85, H 3.47, N 18.35.
Herbicidal activity screening
Herbicidal activities of target compounds with
Chlorsulfuron as a positive control against the root
growth of Brassica campestris and the seedling growth
of Echinochloa crusgalli at 100 μg/mL and 10 μg/mL
respectively were screened and evaluated referring to
the literatures.[15,16] In the meanwhile, the herbicidal
activities against the growth of weeds Brassica napus,
Amaranthus retroflexus, Echinochloa crusgalli and Dig-
itaria sanguinalis through pre-emergence and post-
emergence in the pot experiment were further tested in
our laboratory as previously reported.[17,18]
General synthetic procedure for target compound I-5
A mixture of intermediate 11 (1.20 g, 3.0 mmol),
Pd(OH)2/C (0.20 g) in tetrahydrofuran (THF, 30 mL)
was stirred for 8 h in hydrogen environment at room
temperature. The progress was monitored by TLC. After
completion of the reaction, the solution was concentrat-
ed and purified through chromatography on silica gel
using petroleum ether/ethyl acetate (V/V＝3∶1) as el-
uent to give white solid I-5. Intermediate 11 was ob-
tained according to our previous work.[12]
Soil degradation investigation
The soil degradation of Chlorsulfuron derivatives
I-1－I-9 was investigated in a red acid soil sampled
from Ji’an city (Jiangxi province, China) with the pH
value of 5.41, the initial additive concentration of 5 mg
a.i./kg under laboratory conditions at 25 ℃ and a
moisture content corresponding to 70% field capacity.
All samples were analyzed on a Shimadzu LC-20AT
HPLC equipped with a binary gradient pump (Shimadzu,
LC-20AT), an UV/VIS detector (Shimadzu, SPD-20A),
an auto sampler (Shimadzu, SIL-20A), a column oven
(Shimadzu, CTO-20AC), a Shimadzu shim-pack VP-
ODS column (5 μm, 250 mm×4.6 mm) connected to a
Shimadzu shim-pack GVP-ODS (10 mm×4.6 mm)
precolumn, and a computer (model Dell) for carrying
out the analysis. Data were collected and processed by
using an HPLC data system Shimadzu Labsolutions.
The analytical conditions for HPLC were as follows: the
mobile phases consisted of methanol (A) and phosphor-
ic acid solution in double distilled water (B) (pH 3.00)
with a flow rate of 0.8－1.0 mL/min, the temperature of
column oven was set at 25 ℃, the injection volume was
10 μL, and the detector wavelength was adjusted at 235
nm according to the UV spectra of the target compounds.
The specific HPLC analytical conditions, which could
ensure good separation between soil contaminants and
standard samples, were listed in Table 1. For the anal-
yses of soil samples, the following gradient was used for
separation: at 0－20.00 min, collecting data with the
corresponding mobile phases and flow rate; 20.10－
1-(2-Chloro-5-aminophenylsulfonyl)-3-(4-meth-
oxy-6-methyl-1,3,5-triazin-2-yl)urea (I-5)
White
granules, yield 86%, m.p. 178－180 ℃; 1H NMR (ace-
tone-d6, 400 MHz) δ: 12.69 (s, 1H, SO2NH), 9.60 (s, 1H,
NHCONH), 7.38 (d, J＝2.8 Hz, 1H, Ph-H), 7.11 (d, J＝
8.6 Hz, 1H, Ph-H), 6.80 (dd, J＝8.6, 2.8 Hz, 1H, Ph-H),
5.24 (s, 2H, NH2), 3.89 (s, 3H, Ar-OCH3), 2.37 (s, 3H,
Ar-CH3); 13C NMR (d6-acetone, 101 MHz) δ: 178.8,
170.8, 164.3, 148.1, 147.9, 136.6, 132.0, 119.6, 117.4,
116.6, 54.9, 24.6; UV-vis (CH2Cl2) λmax: 234 nm. m/z
(ESI) [MH] calcd for C12H12ClN6O4S: 371.0, found
370.9. Anal. calcd for C12H13ClN6O4S: C 38.66, H 3.51,
N 22.54; found C 38.49, H 3.21, N 22.72.
General synthetic procedure for target compound I-6
To a solution of compound I-5 (0.40 g, 1.1 mmol) in
tetrahydrofuran (THF, 20 mL) was added methanesul-
fonic anhydride (0.22 g, 1.3 mmol) at 0 ℃. The mixture
was stirred for 3 h, and turned to reddish brown solution.
The progress was monitored by TLC. After reaction
completion, the mixture was concentrated and purified
through chromatography on silica gel using petroleum
ether/ethyl acetate (V∶V＝1∶1) as eluent to give
white solid I-6.
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Controllable Effect of Structural Modification of Sulfonylurea Herbicides on Soil Degradation
50.00 min, 100% A used to flush the column; 50.10－
75.00 min, corresponding mobile phases and flow rate
used for balancing the instrument before next injection.
For quantitative analysis, stock solutions (200 μg/mL)
of each individual standard were prepared by dissolving
accurate amounts of pure compound (10.0 mg) in ace-
tonitrile (50 mL). Working standard solutions obtained
by further dilution of stock solutions with acetonitrile
were used to generate the external standard response
calibration curves for subsequent measurement of con-
centration of target compounds in soil at different
time.[19,20] Under these conditions, the appropriate ex-
traction solvents were selected according to measured
soil recovery rates and coefficients of variation (Table
1). After the analytical conditions and extraction sol-
vents were determined, the soil degradation behaviors
were investigated using the following methods.
Testing soil (20.00 g, air-dry weight) passed through
2 mm sieve was weighed into six groups of 150 mL Er-
lenmeyer flasks, three in each group respectively, and
added standard solutions at a concentration of 5 mg
a.i./kg. Following the solvent volatilizing completely
under a fume hood, the soil was thoroughly mixed, and
an appropriate volume of distilled water was added to
adjust the soil moisture content to approximately 70%
field capacity. The bottles were then stoppered with a
cotton plug and put into an ecological incubator (tem-
perature (25±1) ℃, humidity 80%) to incubate in the
Table 1 Analytical conditions for the soil degradation of target compoundsa
HPLC analysis conditions
(wavelength, flow rate,
mobile phase (V/V))
Adding mass
Average recov- Coefficient of
Comp. R
Extraction solvents (V/V)
1
ery rate/%
variation/%
fraction/(mg•kg )
5
87.96
85.69
75.46
78.78
75.28
71.72
78.61
77.17
78.24
84.66
82.74
77.56
NA
1.91
1.92
3.53
1.53
3.01
2.48
4.76
3.62
4.25
2.38
1.91
4.23
NA
235 nm, 1.0 mL/min,
acetone/DCM/phosphoric acid
H
2
I-1
I-2
I-3
I-4
I-5
I-6
I-7
I-8
I-9
CH3OH/H2O (pH 3.0)＝55/45 aqueous solution (pH 2.0)＝40/5/5
0.5
5
235 nm, 0.8 mL/min,
acetone/DCM/phosphoric acid
N(CH3)2
NHCOCH3
OCH3
2
CH3OH/H2O (pH 3.0)＝65/35 aqueous solution (pH 2.0)＝40/5/5
0.5
5
acetone/THF/DCM/methanol/
235 nm, 1.0 mL/min,
phosphoric acid aqueous solution
CH3OH/H2O (pH 3.0)＝55/45
2
(pH 2.0)＝30/10/10/5/10
0.5
5
235 nm, 0.8 mL/min,
acetone/DCM/phosphoric acid
2
CH3OH/H2O (pH 3.0)＝65/35 aqueous solution (pH 2.0)＝40/5/5
0.5
5
235 nm, 1.0 mL/min,
NA
CH3OH/H2O (pH 3.0)＝50/50
NH2
2
NA
NA
0.5
5
NA
NA
acetone/THF/DCM/methanol/
235 nm, 1.0 mL/min,
phosphoric acid aqueous solution
CH3OH/H2O (pH 3.0)＝55/45
81.35
76.32
82.31
88.77
83.85
72.60
91.15
83.53
74.81
91.49
89.77
83.63
4.00
3.14
3.47
1.24
2.67
1.56
2.13
1.87
3.67
1.32
1.31
1.85
NHSO2CH3
N(C2H5)2
2
(pH 2.0)＝30/10/10/5/10
0.5
5
235 nm, 1.0 mL/min,
acetone/DCM/phosphoric acid
2
CH3OH/H2O (pH 3.0)＝70/30 aqueous solution (pH 2.0)＝40/5/5
0.5
5
235 nm, 0.8 mL/min,
acetone/DCM/phosphoric acid
-CH＝CH2
-CH＝
2
CH3OH/H2O (pH 3.0)＝70/30 aqueous solution (pH 2.0)＝40/5/5
0.5
5
235 nm, 0.8 mL/min,
acetone/DCM/phosphoric acid
2
N-OCH3 CH3OH/H2O (pH 3.0)＝60/40 aqueous solution (pH 2.0)＝40/5/5
0.5
a I-1 represents Chlorsulfuron, and the determination of soil recovery rates was performed in quintuplet at each adding mass fraction to
calculate the average recovery rate and coefficient of variation. NA represents no suitable extraction solvents for I-5.
Chin. J. Chem. 2016, XX, 1—8
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5

Hua et al.
FULL PAPER
dark prior to treatment. In the cultivating process, the
moisture content in Erlenmeyer flask was adjusted reg-
ularly to maintain the original water-holding state. The
samples were taken periodically and added the corre-
sponding extraction solvent. The mixture was shaken
for 3 h at 200 r/min with an oscillator, and then centri-
fuged for 2 min at 6500 r/min with a Thermo Scientific
Legend Mach 1.6 R centrifuge to obtain supernatant
which was concentrated later in vacuum at room tem-
perature. After the residue was extracted by dichloro-
methane (30 mL×2), the combined organic layer was
dried by anhydrous sodium sulfate, filtered and concen-
trated up to dryness. The product was dissolved in ace-
tonitrile (10 mL), and filtered through a filter membrane
(0.22 μm) to HPLC analysis. Each sample was taken six
times for drawing first-order kinetic curves, and every
time was performed in triplet for statistical analysis.
Finally, the soil degradation results of target com-
pounds were described by first-order kinetic curves ac-
cording to the following equation:
were characterized by ultraviolet spectra (UV), 1H NMR,
13C NMR, elemental analysis (EA), and mass spectra
(MS).
Herbicidal activity
The herbicidal activities of target compounds with
Chlorsulfuron as a positive control against the root
growth of Brassica napus and the seedling growth of
Echinochloa crusgalli at 100 μg/mL and 10 μg/mL re-
spectively were shown in Table 2 and comprehensively
evaluated. From the data, it was concluded that most of
the target compounds exhibited good herbicidal activi-
ties in comparison with Chlorsulfuron except structures
I-3 (5-NHCOCH3) and I-6 (5-NHSO2CH3). In order to
further determine the herbicidal activities of target
compounds, the bioassays were tested and evaluated
against the growth of four weeds representing monocot-
yledonous and dicotyledonous plants through the pot
experiment where pre-emergence and post-emergence
were both adopted at 150 g/ha and 30 g/ha respectively,
and the bioassay results were displayed in Table 3. As
can be seen from the table, in a given category, no mat-
ter pre-emergence or post-emergence, the herbicidal
activities of target compounds against Brassica napus,
Amaranthus retroflexus, Echinochloa crusgalli were
higher than those against Digitaria sanguinalis, includ-
ing positive control Chlorsulfuron (I-1). Surprisingly,
even if the herbicidal activities against other test weeds
were superior, the structure I-7 (5-N(C2H5)2) exhibited
even better biological activity against Digitaria sangui-
nalis than Chlorsulfuron with the inhibition percent of
99.5% at 150 g/ha and 93.9% at 30 g/ha during
post-emergent experiment. In addition, the target com-
pounds adopted post-emergence treatment in general
showed more excellent herbicidal activities than those
employed pre-emergence. Overall, most compounds
displayed outstanding herbicidal activities except struc-
ture I-6 when compared with Chlorsulfuron. These re-
sults revealed that the introduction of specific substitu-
ents at 5th position in the benzene ring was favorable to
kt
e
C
C
0
＝
×
t
where C0 is the initial concentration of the test com-
pounds in soil, Ct is the concentration at time t and k is
the first-order rate constant. The first-order degradation
half-life (t1/2) was calculated from ln (2)/k.
Results and Discussion
Synthetic chemistry
Herein, the important intermediates II were designed
and synthesized according to the methods in Scheme 2.
Firstly, 2-chloro-5-acetamidophenylsulfonamide (II-3)
was prepared through the reaction of 2-chloro-5-amino-
phenylsulfonamide (4) with acetic anhydride in di-
chloromethane (DCM). Intermediate 4 was obtained
through the diazotization of material 2-chloro-5-nitro-
benzenamine (1),[21] nucleophilic substitution reaction
of 2-chloro-5-nitrophenylsulfonyl chloride (2) and 25%
－28% ammonium hydroxide,[22] and reduction of nitro
group with Fe/HCl.[23] Synthesis of 2-chloro-5-meth-
oxyphenylsulfonamide (II-4) from material 1-chloro-
4-methoxy-2-nitrobenzene (5) usually involved reduc-
tion of nitro group with sodium hyposulfite, diazotiza-
tion of amine and nucleophilic substitution reaction of
sulfonyl chloride and 25%－28% ammonium hydroxide.
2-Chloro-5-diethylaminophenylsulfonamide (II-7) was
prepared by a process starting from ethylation of amino
group in structure 4 with sodium cyanoborohydride,
40% acetaldehyde aqueous solution and acetic acid in
acetonitrile at room temperature,[24] followed by protec-
tion of sulfonamide with N,N-dimethylformamide di-
methyl acetal (DMF-DMA),[25,26] then the second ethyl-
ation at 50 ℃, and finally deprotection with 80% hy-
drazine hydrate in ethanol.[27] The synthetic routes to-
wards the target compounds I were summarized in
Scheme 1. Subsequently, five novel molecules were
synthesized in various ways and the obtained structures
Table 2 Herbicidal activities (%) of the target compounds
against the root growth of Brassica napus and the seedling
growth of Echinochloa crusgalli a
Brassica napus
Echinochloa crusgalli
Comp.
100 μg/mL 10 μg/mL
100 μg/mL 10 μg/mL
I-1
I-3
I-4
I-5
I-6
I-7
I-8
I-9
72.9
65.6
80.9
77.5
68.5
74.3
76.0
74.6
70.3
34.7
69.2
74.4
34.4
65.4
61.6
67.6
60.0
43.0
50.0
57.0
15.0
60.0
30.0
45.0
46.0
5.0
37.0
50.0
5.0
55.0
25.0
40.0
a Compound I-1 represents Chlorsulfuron.
6
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Chin. J. Chem. 2016, XX, 1—8

Controllable Effect of Structural Modification of Sulfonylurea Herbicides on Soil Degradation
remain or improve the herbicidal activities of the re-
vised structures.
the introduction of electron-donating acetamido (I-3),
methoxy (I-4), diethylamino (I-7) and vinyl (I-8) groups
at 5th position of the benzene ring accelerated the soil
degradation rates of revised structures in comparison
with Chlorsulfuron, which further confirmed our previ-
ous assumption that the introduction of various substit-
uents at 5th position of the benzene ring does influence
the soil degradation rates of target compounds where
electron-donating groups distinctly increase their deg-
radation rates. For the influence of different substituted
amino groups on soil degradation rates, we found that
the introduction of dimethylamino (I-2) and diethyla-
mino (I-7) groups at 5th position was more conducive to
accelerate the soil degradation rates than other investi-
gated substituents when compared with Chlorsulfuron
with the corresponding half-lives to 0.43 and 1.60 d re-
spectively, which could provide valuable information to
explore potential controllable degradation of other
Soil degradation
The soil degradation behaviors of target compounds
were investigated under set conditions and the specific
multivariate mixed extraction solvents (acetone/DCM/
phosphoric acid aqueous solution and acetone/THF/
DCM/methanol/phosphoric acid aqueous solution) were
firstly selected to obtain high soil recovery rates. Finally,
the corresponding first-order kinetic equations and
half-life periods of soil degradation were shown in Ta-
ble 4, where Chlorsulfuron (I-1) and compound I-2
(5-dimethyl) were both employed as positive controls.
Unfortunately, the soil degradation behavior of com-
pound I-5 (5-NH2) was not investigated with the reason
that no suitable extraction methods were found out to
get eligible recovery rate. From the table, on the whole,
Table 3 Herbicidal activities (%) of the target compounds in the pot experiment
Herbicidal activity (inhibition percent)/%
Pre-emergence
Brassica Amaranthus Echinochloa Digitaria
Post-emergence
Concentration/
(g a.i.•ha1)
Comp.
Brassica Amaranthus Echinochloa Digitaria
napus
96.5
97.2
65.7
73.4
95.1
98.6
83.2
86.7
30.1
44.1
97.9
98.6
81.8
88.1
62.2
81.8
retroflexus crusgalli
sanguinalis
napus
100
100
90.7
100
100
100
100
100
42.2
65.8
100
100
100
100
94.5
100
retroflexus
crusgalli
80.3
100
sanguinalis
43.9
73.5
10.5
30.6
14.3
51.0
50.0
60.2
0
30
79.2
91.7
56.9
97.2
73.6
86.1
68.1
76.4
0
82.4
86.4
53.4
84.1
61.9
78.4
63.1
85.8
12.5
13.6
81.8
88.6
36.9
55.1
23.9
33.5
0
100
I-1
I-3
I-4
I-5
I-6
I-7
I-8
I-9
150
30
21.4
0
100
80.0
87.2
92.3
100
100
150
30
11.4
0
100
90.2
100
150
30
10.5
0
95.0
100
100
150
30
0
100
0
38.9
59.6
93.0
100
14.8
62.7
100
150
30
13.9
63.9
76.4
54.2
70.8
58.3
63.9
0
6.1
10.5
40.8
0
93.9
99.5
0
150
30
100
100
64.6
100
150
30
5.3
0
100
0
90.0
95.0
62.0
98.7
0
150
0
0
Table 4 Kinetic parameters for the soil degradation of target compounds
Comp.
I-6
R
H
First-order kinetic equation
R2
t1/2/d
NHSO2CH3
Ct＝3.8828e0.0474t
Ct＝4.2798e0.0537t
Ct＝4.5170e0.0636t
Ct＝4.0179e-0.0644t
Ct＝4.5661e0.0742t
Ct＝4.0782e0.0917t
Ct＝4.4083e0.4323t
Ct＝4.0341e1.6117t
0.9976
0.9995
0.9990
0.9991
0.9990
0.9912
0.9938
0.9955
14.62
12.91
10.90
10.76
9.34
I-1
I-4
OCH3
I-3
NHCOCH3
-CH＝N-OCH3
-CH＝CH2
N(C2H5)2
I-9
I-8
7.56
I-7
1.60
I-2
N(CH3)2
0.43
R2: Correlation coefficient; t1/2: Half-life.
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7

Hua et al.
FULL PAPER
herbicides. In addition, the soil degradation rate of
compound I-9 was also increased with the half-life to
9.34 d, which was shorter than that of Chlorsulfuron (t1/2
＝12.91 d). This may be due to the easy decomposition
of methoxyiminomethyl group in this acid soil.
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Figure 3 The relationship of structures, herbicidal activity and
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Acknowledgement
This work was financially supported by the National
Natural Science Foundation of China (No. 21272129),
Collaborative Innovation Center of Chemical Science
and Engineering (Tianjin), and Syngenta Doctorate
Scholarship.
(Lu, Y.)
8
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