Synthesis and biological activity of novel phenyltriazolinone derivatives

Article abstract of DOI:10.3390/molecules15129024

Phenyltriazolinones are one of the most important classes of herbicides targeting the protoporphyrinogen oxidase enzyme. A series of triazolinone derivatives containing a strobilurin pharmacophore were designed and synthesized with the aim of discovering new phenyltriazolinone analogues with high activity. The herbicidal activity of the synthesized compounds was assayed and some of the test compounds displayed moderate herbicidal activity at 150 g ai/ha.

Full text of DOI:10.3390/molecules15129024

Molecules 2010, 13, 9024-9034; doi:10.3390/molecules15129024
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis and Biological Activity of Novel
Phenyltriazolinone Derivatives
Qiongyou Wu *, Guodong Wang, Shaowei Huang, Long Lin and Guangfu Yang
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry,
Central China Normal University, Wuhan 430079, Hubei, China
* Author to whom correspondence should be addressed; E-Mail: qywu@mail.ccnu.edu.cn;
Tel.: +86-27-67867706, Fax: +86-27-67867141.
Received: 27 October 2010; in revised form: 18 November 2010 / Accepted: 22 November 2010 /
Published: 9 December 2010
Abstract: Phenyltriazolinones are one of the most important classes of herbicides targeting
the protoporphyrinogen oxidase enzyme. A series of triazolinone derivatives containing a
strobilurin pharmacophore were designed and synthesized with the aim of discovering new
phenyltriazolinone analogues with high activity. The herbicidal activity of the synthesized
compounds was assayed and some of the test compounds displayed moderate herbicidal
activity at 150 g ai/ha.
Keywords: phenyltriazolinones; strobilurin; herbicidal activity; protoporphyrinogen oxidase
1. Introduction
Triazolinones are attractive building blocks of considerable interest because of their unique
properties and wide range of biological properties [1-6], such as human neurokinin-1 receptor
antagonist [7] and angiotensin AII receptor antagonist [8-9] activity. In the past two decades, research
on triazolinone herbicides has attracted continuous interest [10-14] since the discovery of
sulfentrazone, the first commercialized phenyltriazolinone herbicide with excellent pre-emergence
control of several broadleaf weeds as well as several selected grass weeds for the soybean market [15].
Carfentrazone-ethyl, a second commercial herbicide introduced by FMC only a few years after
sulfentrazone was marketed, showed excellent post-emergence cereal and corn herbicidal
activities [16]. Nowadays, phenyltriazolinone herbicides play an important role in the herbicide
market. The mode of action of sulfentrazone and carfentrazone-ethyl is the inhibition of

Molecules 2010, 13
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protoporphyrinogen oxidase (Protox), which causes the accumulation of protoporphyrin IX (Proto IX),
which is involved in the light-dependent formation of singlet oxygen responsible for membrane
peroxidation [17-18]. This unique mode of action, that makes phenyltriazolinones safe, high efficient
and environmentally benign herbicides, has been actively pursued and Protox inhibitors have been
used very effectively for many decades, although a biotype of Amaranthus tuberculatus has recently
evolved resistance to these herbicides via a codon deletion mutation that affects the binding of the
inhibitors to the enzyme [19-20].
Structure-activity relationship analysis indicated that the 2,4,5-trisubstituted phenyl structure plays
an important role for their herbicidal activities of phenyltriazolinones. Among the phenyl substitution
patterns investigated, F or Cl at C-2 and Cl at C-4 was identified as crucial for most the active
compounds, while a wide range of substitutions at C-5 were acceptable. Additionally, among the N-4
substituents investigated, the CHF2 group always gave the highest herbicidal activity, although the
success of azafenidin indicated that groups other than CHF2 are also acceptable at N-4 [21].
The strobilurins are a class of fungicidal compounds which have been applied as agricultural
disinfectants in many countries. Most active strobilurin compounds contain the same biologically
active moiety, that is, an acrylate, an acetate, or an acetamide chemical group with the E configuration
about the double bond in the toxophore moiety [22-24]. We envisaged that, if the strobilurin
pharmacophore was introduced into the phenyltriazolinone scaffold, the resulting product (Figure 1,
compounds 1) should be an interesting lead structure for agrochemical development. In our previous
studies [25], we have introduced the (E)-methyl 2-methoxyimino-2-o-tolylacetate toxophore into the
N-4 position of sulfentrazone and the resulting compound Y5060 showed comparable herbicidal
activity at 75-150 g of active ingredient/ha with the commercial product sulfentrazone. On the basis of
test results of herbicidal spectrum and crop selectivity, compound Y5060 was verified as a promising
candidate for further development as a postemergence herbicide. To further improve the herbicidal
activity of this class of compounds and screen for valuable lead compounds, according to the
bioisosteric principle, a series of new compounds were designed and synthesized.
Figure 1. Structures of sulfentrazone, carfentrazone-ethyl, azafenidin, Y5060 and the new
compounds synthesized in this study.
O
Cl
O
Cl
O
Cl
CHF2
CH3
CHF2
CH3
N
N
Cl
Cl
N
N
Cl
N
Cl
N
N
N
N
O
H3CO2SHN
C2H5O
Carfentrazone-ethyl
Azafenidin
Sulfentrazone
O
OCH3
O
N
H3CO
O
X
O
F
M
N
N
Cl
N
Cl
EtO2SHN
N
N
CH3
N
CH3
R1HN
1, X = F or Cl,
See Table 1 for the R1 and M substitution
Y 5060

Molecules 2010, 13
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2. Results and Discussion
The preparation of the key intermediates 4 starts with an appropriately substituted aniline which is
converted into the corresponding phenylhydrazine by diazotization with NaNO2 in concentrated HCl
solution at low temperature and subsequently reduced with SnCl2 [10]. The phenylhydrazines were
then treated with a ketocarboxylic acid without separation to afford phenylhydrazone 3, which
undergoes a Schmidt rearrangement upon reaction with diphenylphosphoryl azide and is thus
converted into the corresponding triazolinone 4. Thereafter, the benzene ring of the intermediate 4 is
nitrated with the common mixed H2SO4 and HNO3 nitration reagent and the nitro group was then
reduced with iron powder to form the aromatic amine 6, which is then treated with the corresponding
sulfonyl chloride in the presence of a weak base such as triethylamine to provide sulfonyl amide 7. It
was noticed that the hydrogen on 4-N position of the triazolinone ring is also replaced during the
treatment with the chloride.
Scheme 1. Synthetic route of the target compound 1.
X
O
X
CH3
X
i) NaNO2, HCl
ii) SnCl2, HCl
N
NH
(PhO)2PON3
NH
Cl
N
N
Cl
O
Cl
NH2
iii) CH3COCOOH
HO
CH3
4
2
3
X
O
X
O
RSO2Cl, Et3N
CH3
Fe, NH4Cl
H2SO4, HNO3
NH
NH
Cl
N
N
Cl
N
N
CH3
NH2
NO2
6
5
X
O
X
O
SO2R
CH3
M
M, K2CO3, DMF
N
N
Cl
N
Cl
RO2S NH
N
N
N
CH3
RO2S N
SO2R
1
7
Initially, we selected three typical strobilurin pharmacophores (M1-3) [26-27] as substituents to be
introduced at the 4-N position of triazolinone 7 to investigate the effect of these substitution patterns
on their herbicidal activity. The preparation of intermediate M1 was achieved in five steps with simple
2-o-tolylacetic acid as starting material (Scheme 2).
Scheme 2. Synthesis of the intermediate M1.
O
O
O
HOOC
H3C
H3CO
Br
OMe
H3CO
H3C
OMe
H3CO
H3C
OH
i) MeOH, H2SO4
ii) HCO2CH3
NBS, AIBN
MeOH, K2CO3
M1

Molecules 2010, 13
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The methyl 2-o-tolylacetate was treated with methyl formate in the presence of sodium methoxide
to afford the mixed enol (E/Z), which can be methylated with dimethyl sulfate to give the desired
E-isomer stereoselectively and successively brominated with NBS to afford the methoxymethyl
acrylate M1 in excellent yield.
For the synthesis of intermediate M2 (Scheme 3), the selected starting material was 2-bromotoluene,
which was first converted into the Grignard reagent and then underwent nuclophilic addition with
dimethyl oxalate to form methyl 2-oxo-2-o-tolylacetate, which after treatment with methoxylamine
provided a mixed oxime. The E/Z ratio in the crude mixture was determined by 1H-NMR spectroscopy
as ca. 1:1. After further column chromatography purification, the pure E-isomer was obtained in 51%
yield. Similarly, the bromination of the E-oxime with 1.2 equiv. NBS afford target intermediate
M2 smoothly.
Scheme 3. Synthesis of the intermediate M2.
O
O
O
N
O
N
Br
H3CO
Br
OCH3
H3CO
H3C
H3CO
H3C
OCH
3 NBS, AIBN
.
i) Mg, THF
MeONH2 HCl
H3C
ii) (COOCH3)2
M2
The third intermediate M3 was prepared according to the procedure shown in Scheme 4. Firstly,
2-nitrotoluene was converted into N-hydroxy-2-methylbenzenamine by reduction with zinc in aqueous
NH4Cl solution to give N-hydroxybenzenamine which undergoes nucleophilic substitution with methyl
chloroformate to afford the N-acetylated product and subsequently the free N-hydroxy group was
methylated with dimethyl sulfate to give the methoxycarbamate product, which was then transformed
into intermediate M3 with NBS.
Scheme 4. Synthesis of the intermediate M3.
O
O
O
OH
OCH3
OCH3
NO2
H3CO
H3C
N
H3CO
Br
N
H3CO
H3C
N
i) Zn, NH4Cl
Me2SO4, K2CO3
NBS, AIBN
H3C
ii) ClCO2CH3, NaHCO3
M3
With these key intermediates in hand, we then investigated the coupling reaction of these
intermediates M1-3 with the sulfonyl group protected phenyltriazolinone 7. First, we tried a two-step
synthetic procedure by treating compound 7 bearing three RSO2- groups with a base such as NaOH to
obtain the 4-N deprotected product, which subsequently underwent nucleophilic substitution with
intermediates M1-3 to give the desired products, albeit in very low yield (17 %). Meanwhile, if we
combined the two-step reaction into a one-pot version, we found that the RSO2-group can be removed
readily by treatment with a weak base such as K2CO3, after which the appropriate M substitution can
be concomitantly introduced at the 4-N position of the triazolinone ring. Thus, compounds 1a～1q
were smoothly prepared in moderate to good yield (Table 1).

Molecules 2010, 13
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Table 1. Structure of the synthesized target molecules 1.
X
O
M
N
Cl
N
N
CH3
RO2SHN
No.
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
X
F
F
R
CH3-
CH3CH2-
Ph-
Ma
m.p. (°C)
153-155
167-169
187-190
138-140
168-170
194-196
138-140
164-166
150-152
162-164
190-192
186-188
166-168
oil
Yield (%)
52
M1
M1
M1
M1
M1
M1
M2
M2
M2
M2
M2
M3
59
F
39
Cl
Cl
Cl
F
CH3-
CH3CH2-
Ph-
78
80
48
75
CH3-
F
Ph-
CH3-
CH3CH2-
Ph-
CH3-
CH3CH2-
Ph-
46
73
79
44
57
55
41
62
Cl
Cl
Cl
F
F
F
Cl
Cl
Cl
M3
M3
M3
M3
M3
CH3SO2-
189-191
174-176
oil
CH3CH2SO2-
70
46
PhSO2-
O
O
O
O
O
N
O
O
N
O
O
M3:
M2:
M1:
a:
The herbicidal activities of compounds 1a～1q against monocotyledon weeds such as Echinochloa
crusgalli (EC), Digitaria sanguinalis (DS), Poa annua (PA) and dicotyledon weeds such as Brassica
juncea (BJ), Amaranthus retroflexus (AR), and Eclipta prostrate (EP) were evaluated according to a
previously reported procedure [28]. Sulfentrazone was selected as a control. Most of the test
compounds did not show the desired herbicidal activity at 150 g of ai/ha. However, some compounds
present a certain degree of herbicidal activity. For example, compounds 1k, 1l and 1m exhibited 70%
activity against E. prostrate, compounds 1p and 1q displayed moderate herbicidal activity against E.
crusgalli, D. sanguinalis and P. annua. In comparison, their herbicidal activity is lower than that of the
lead compound Y5060.
In conclusion, several strobilurin type pharmacophores were introduced to the 4-N position of the
phenyl triazolinone scaffold with the view of preparing and screening potentially highly herbicidal
lead compounds. The herbicidal activity of these synthesized compounds against six weeds was
investigated. Unfortunately, they did not display desired weeds control potential compared to the lead
compound Y5060.

Molecules 2010, 13
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3. Experimental
3.1. General
Unless otherwise noted, all materials were commercially available and were used directly without
further purification. All solvents were redistilled before use. 1H-NMR spectra were recorded at 400 MHz
on a Mercury-Plus 400 spectrometer in CDCl3 (unless stated otherwise) with tetramethylsilane as the
internal reference. MS spectra were determined using a Trace MS 2000 organic mass spectrometry.
Elementary analyses were performed on a Vario EL III elementary analysis instrument. Melting points
were taken on a Buchi B-545 melting point apparatus and uncorrected.
3.2. General Procedure for the Preparation of Phenylhydrazines 3
To a cold solution of the appropriate 2,4-disubstituted benzenamine (0.10 mol) in concentrated
HCl (100 mL), aqueous NaNO2 (8.5 g, 0.10 mol) was added dropwise during a period of 0.5 h under Ar.
The result solution was stirred for a further 1 h at −9 °C, then a solution of SnCl2 in conc. HCl (40 mL)
was added slowly over 40 min. After stirring for an another 0.5 h at −9 °C, the ice-salt bath was
removed and the reactants were allowed to slowly warm to room temperature and then stirred at room
temperature for 2 h. Then water (80 mL) and pyruvate (8.8 g, 0.05 mol) in water (80 mL) were added.
The result reaction mixture was stirred for 30 min. The precipitate was collected and dried to give the
phenylhydrazine 3. 3a, X = F, yield, 83%, m.p., 176-178 °C (lit: 172-173 °C [29]), 3b, X = Cl, yield,
89%，m.p., 188-190 °C (lit: 193-194 °C [29]).
3.3. General Procedure for the Synthesis of Phenyltriazolinones 4
To a mixture of phenylhydrazone 3 (0.05 mol) and triethylamine (5.1 g, 0.05 mol) in toluene (30 mL)
was slowly added diphenyl phosphorous azide (13.75 g, 0.05 mol). The mixture was refluxed until the
reaction was complete according to the TLC monitoring. The reactants were cooled to room
temperature and extracted with 1 M NaOH solution (50 mL). The water layer was separated and
neutralized with concentrated HCl. The white precipitate was collected by filtration, washed with water
and dried to afford the product 4. 4a, X = F, yield, 75%，m.p. 204-206 °C (lit: 201-203 °C [29]),
1H- NMR: δ 2.29 (s, 3H, CH3), 7.24 (q, 1H, ArH), 7.27 (d, 1H, ArH), 7.47 (t, 1H, ArH), 11.64 (s, 1H,
NH); 4b, X = Cl, yield, 92%，m.p. 179-181 °C (lit: 174-175 °C [14])，1H-NMR: δ 2.18 (s, 3H, CH3),
7.35 (q, 1H, ArH), 7.47 (d, 1H, ArH), 7.27 (d, 1H, ArH), 11.49 (s, 1H, NH).
3.4. General Procedure for the Synthesis of Nitrophenyltriazolinones 5
To a stirred solution of phenyltriazolinone 4 (5.00 mol) in concentrated H2SO4 (10 mL) was added
concentrated HNO3 (0.45 g) slowly at 0 °C. After stirring for 0.5 h at this temperature, the mixture was
allowed to warm to room temperature and stirred for a further 1 h, then the reaction mixture was
poured into ice water and the precipitate was collected and dried to afford the desired product 5. 5a,
X = F, yield, 95%, 1H-NMR: δ 2.32 (s, 3H, CH3), 7.47 (d, 1H, J = 9.2 Hz, ArH), 8.30 (d, 1H, J = 6.8 Hz,
ArH), 11.40 (s, 1H, NH); 5b, X = Cl，yield, 98%，1H-NMR: δ 2.13 (s, 3H, CH3), 6.84 (s, 1H, ArH),
7.45 (s, 1H, ArH), 11.61 (s, 1H, NH).

Molecules 2010, 13
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3.5. General Procedure for the Synthesis of Aminophenyltriazolinones 6
A mixture of nitrophenyltriazolinone 5 (0.01 mol) and NH4Cl (0.55 g) in ethanol (25 mL) and
water (3 mL) was refluxed for 0.5 h. Iron powder (1.68 g, 0.03 mol) was then added to the refluxing
solution in several portions. The reaction was monitored by TLC until the starting material was
consumed. The reaction mixture was filtrated through diatomite and washed with ethanol. The
combined filtrate was concentrated to a half volume and the precipitate was collected to afford the
product. 6a, X = F, yield, 75%. 1H-NMR (DMSO): δ 2.15 (s, 3H, CH3), 5.41(s, 2H, NH2), 6.89 (d, 1H,
J = 7.2 Hz, ArH), 7.32 (d, 1H, J = 10.4 Hz, ArH), 11.68 (s, 1H, NH); 6b, X = Cl, yield, 84%, 1H-NMR
(DMSO): δ 2.12 (s, 3H, CH3), 5.77 (s, 2H, NH2), 6.86 (s, 1H, ArH), 7.44 (s, 1H, ArH), 11.73 (s, 1H, NH).
3.6. General Procedure for the Synthesis of Compound 7
To a solution of compound 6 (0.01 mol) and triethylamine (0.03 mol) in CH2Cl2 (25 mL) was
added dropwise the appropriate sulfonyl chloride (0.03 mol) at 0 °C. The reaction mixture was kept at
0 °C for a further 1.5 h and then washed with water. The combined organic phase was dried with
NaSO4 and evaporated on a rotary evaporator. The residue was chromatographed on silica gel with
ethyl acetate/petroleum ether (1:4) to give product 7 in a yield of 75%~85%.
3.7. General Procedure for the Preparation of Target Molecules 1
A mixture of the appropriate intermediate M (0.006 mol), compound 7 (0.005 mol) and anhydrous
K2CO3 (0.015 mol) in DMF (20 mL) was stirred at room temperature until the reaction was complete
according to TLC. The reaction mixture was poured into ice water (200 mL) and extracted with ethyl
acetate. The combined organic phase was dried with NaSO4 and evaporated on a rotary evaporator.
The residue was chromatographed on silica gel with ethyl acetate/petroleum ether (1:5) as eluent to
give the target product.
(E)-methyl 2-(2-((1-(4-chloro-2-fluoro-5-(methylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-
1
triazol-4(5H)-yl)methyl)phenyl)-3-methoxyacrylate (1a): H-NMR: δ 1.92 (s, 3H, CH3), 3.11 (s, 3H,
SO2CH3), 3.64 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 4.69(s, 1H, CH2), 4.98 (s, 1H, CH2), 6.80 (s, 1H, NH),
7.26 (d, 1H, J = 7.2Hz, ArH), 7.31-7.35 (m, 4H, ArH), 7.58 (d, 1H, CH=), 7.91(d, 1H, J = 6.6 Hz, ArH).
EI-MS (m/z) 524 [M]+. Anal. Calcd. for C22H22ClFN4O6S: C, 50.34, H, 4.22, N, 10.67. Found: C, 50.82,
H, 4.35, N, 10.32.
(E)-methyl 2-(2-((1-(4-chloro-5-(ethylsulfonamido)-2-fluorophenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-
1
4(5H)-yl)methyl)phenyl)-3-methoxyacrylate (1b): H-NMR: δ 1.40 (t, 3H, J = 7.2 Hz, CH3), 1.92 (s,
3H, CH3), 3.22 (q, 2H, J = 7.2 Hz, CH2), 3.64 (s, 3H, CO2CH3), 3.88 (s, 3H, OCH3), 4.77 (s, 1H, CH2),
4.98 (s, 1H, CH2), 6.84 (s, 1H, NH), 7.17 (d, 1H, J = 7.2, ArH), 7.25-7.35 (m, 4H, ArH), 7.58 (d, 1H,
CH=), 7.91 (d, 1H, J = 6.6Hz, ArH). EI-MS (m/z) 538 [M]+. Anal. Calcd. for C23H24ClFN4O6S: C,
51.25, H, 4.49, N, 10.40. Found: C, 51.27, H, 4.63, N, 10.06.
(E)-methyl
2-(2-((1-(4-chloro-2-fluoro-5-(phenylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-
1
triazol-4(5H)-yl)methyl)phenyl)-3-methoxyacrylate (1c): H-NMR: δ 1.94 (s, 3H, CH3), 3.66 (s, 3H,

Molecules 2010, 13
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CO2CH3), 3.89 (s, 3H, OCH3), 4.73 (s, 1H, CH2), 4.95 (s, 1H, CH2), 6.88 (s, 1H, NH), 7.12-8.01 (m, 12H,
ArH, CH=). EI-MS (m/z) 587 [M]+. Anal. Calcd. for C27H24ClFN4O6S: C, 55.24, H, 4.12, N, 9.54. Found:
C, 55.56, H, 4.36, N, 9.46.
(E)-methyl
2-(2-((1-(2,4-dichloro-5-(methylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-
1
4(5H)-yl)methyl)phenyl)-3-methoxyacrylate (1d): H-NMR: δ 1.92 (s, 3H, CH3), 3.17 (s, 3H, CH3),
3.66 (s, 3H, CO2CH3), 3.88 (s, 3H, OCH3), 4.72, (s, 1H, CH2), 4.98 (s, 1H, CH2), 6.95 (s, 1H, NH),
7.58 (d, 1H, CH=), 7.17-7.40 (m, 6H, ArH), 7.85 (s, 1H, Ar); EI-MS (m/z) 541 [M]+; Anal. Calcd. for
C22H22Cl2N4O6S: C, 48.81; H, 4.10; N, 10.35. Found: C, 49.12; H, 4.65; N, 9.94.
(E)-methyl 2-(2-((1-(2,4-dichloro-5-(ethylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-4(5H)-
1
yl)methyl)phenyl)-3-methoxyacrylate (1e): H-NMR: δ 1.40 (t, 3H, J = 7.2 Hz, CH3), 1.91 (s, 3H, CH3),
3.22 (q, 2H, J = 7.2 Hz, CH2), 3.64 (s, 3H, CO2CH3), 3.88 (s, 3H, OCH3), 4.64, (s, 1H, CH2), 4.97 (s, 1H,
CH2), 6.89 (s, 1H, NH), 7.17-7.59 (m, 6H, ArH), 7.87 (s, 1H, CH=); EI-MS (m/z) 555 [M]+; Anal. Calcd.
for C23H24Cl2N4O6S: C, 49.74; H, 4.36; N, 10.09. Found: C, 49.95; H, 4.76; N, 9.91.
(E)-methyl
2-(2-((1-(2,4-dichloro-5-(phenylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-
4(5H)-yl)methyl)phenyl)-3-methoxyacrylate (1f): 1H-NMR: δ 1.96 (s, 3H, CH3), 3.66 (s, 3H, CO2CH3),
3.88 (s, 3H, OCH3), 4.66, (s, 1H, CH2), 4.97 (s, 1H, CH2), 6.79 (s, 1H, NH), 7.17-8.09 (m, 12H, ArH,
CH=); EI-MS (m/z) 603 [M]+; Anal. Calcd. for C27H24Cl2N4O6S: C, 53.74; H, 4.01; N, 9.28. Found: C,
54.06; H, 4.37; N, 9.12.
(E)-methyl
2-(2-((1-(4-chloro-2-fluoro-5-(methylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-
1
triazol-4(5H)-yl)methyl)phenyl)-2-(methoxyimino)acetate (1g): H-NMR: δ 2.00 (s, 3H, CH3), 3.06 (s,
3H, CH3), 3.84 (s, 3H, CO2CH3), 4.07 (s, 3H, NOCH3), 4.77 (s, 2H, CH2), 6.74 (s, 1H, NH), 7.17-7.95
(m, 6H, ArH); EI-MS (m/z) 525 [M]+; Anal. Calcd. for C21H21ClFN5O6S: C, 47.96; H, 4.12; N, 13.32.
Found: C, 47.63; H, 4.5; N, 13.17.
(E)-methyl
2-(2-((1-(4-chloro-2-fluoro-5-(phenylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-
triazol-4(5H)-yl)methyl)phenyl)-2-(methoxyimino)acetate (1h): 1H-NMR: δ 2.16 (s, 3H, CH3), 3.87 (s,
3H, OCH3), 4.06 (s, 3H, NOCH3), 4.78 (s, 2H, CH2), 6.76 (s, 1H, NH), 7.17-8.03 (m, 11H, ArH); EI-
MS (m/z) 588 [M]+; Anal. Calcd. for C26H23ClFN5O6S: C, 53.11; H, 3.94; N, 11.91. Found: C, 53.00;
H, 4.04; N, 11.35.
(E)-methyl
2-(2-((1-(2,4-dichloro-5-(methylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-
1
4(5H)-yl)methyl)phenyl)-2-(methoxyimino)acetate (1i): H-NMR: δ 1.99 (s, 3H, CH3), 3.08 (s, 3H,
CH3), 3.84 (s, 3H, OCH3), 4.07 (s, 3H, NOCH3), 4.78 (s, 2H, CH2), 6.74 (s, 1H, NH), 7.17-7.95 (m,
6H, ArH); EI-MS (m/z) 542 [M]+; Anal. Calcd. for C21H21Cl2N5O6S: C, 46.50; H, 3.90; N, 12.91.
Found: C, 46.17; H, 4.01.; N, 12.46.
(E)-methyl
2-(2-((1-(2,4-dichloro-5-(ethylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-
4(5H)-yl)methyl)phenyl)-2-(methoxyimino)acetate (1j): 1H-NMR: δ 1.40 (t, 3H, J = 7.2 Hz, CH3), 2.01
(s, 3H, CH3), 3.22 (q, 2H, J = 7.2 Hz, CH2), 3.86 (s, 3H, OCH3), 4.08 (s, 3H, NOCH3), 4.77 (s, 2H,

Molecules 2010, 13
9032
CH2), 6.89 (s, 1H, NH), 7.17-7.87 (m, 6H, ArH); EI-MS (m/z) 556 [M]+; Anal. Calcd. for
C22H23Cl2N5O6S: C, 47.49; H, 4.17; N, 12.59. Found: C, 47.37; H, 4.47; N, 12.50.
(E)-methyl
2-(2-((1-(2,4-dichloro-5-(phenylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-
1
4(5H)-yl)methyl)phenyl)-2-(methoxyimino)acetate (1k): H-NMR: δ 2.02 (s, 3H, CH3), 3.68 (s, 3H,
OCH3), 3.98 (s, 3H, NOCH3), 4.77 (s, 2H, CH2), 6.75 (s, 1H, NH), 7.17-8.16 (m, 11H, ArH); EI-MS
(m/z) 604 [M]+; Anal. Calcd. for C26H23Cl2N5O6S: C, 51.66; H, 3.84; N, 11.59. Found: C, 51.78; H,
4.05; N, 11.15.
methyl
2-((1-(4-chloro-2-fluoro-5-(methylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-
4(5H)-yl)methyl)phenyl(methoxy)carbamate (1l): 1H-NMR: δ 2.18 (s, 3H, CH3), 3.105 (s, 1H, CH3),
3.76 (s, 3H, CO2CH3), 3.84 (s, 3H, NOCH3), 4.94 (s, 2H, CH2), 6.83 (s, 1H, NH), 7.17-7.91 (m, 6H,
ArH); EI-MS (m/z) 514 [M]+; Anal. Calcd. for C20H21ClFN5O6S: C, 46.74; H, 4.12; N, 13.63. Found: C,
47.09; H, 4.41; N, 13.36.
methyl 2-((1-(4-chloro-5-(ethylsulfonamido)-2-fluorophenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-4(5H)-
1
yl)methyl)phenyl(methoxy)carbamate (1m): H-NMR: δ 1.40 (t, 3H, J = 7.2 Hz, CH3), 2.18 (s, 3H,
CH3), 3.16 (q, 2H, J = 7.2 Hz, CH2), 3.76 (s, 3H, OCH3), 3.84 (s, 3H, NOCH3), 4.94 (s, 2H, CH2), 6.78
(s, 1H, NH), 7.17-7.95 (m, 6H, ArH); EI-MS (m/z) 528 [M]+; Anal. Calcd. for C21H23ClFN5O6S: C,
47.77; H, 4.39; N, 13.27. Found: C, 47.87; H, 4.63; N, 12.97.
methyl 2-((1-(4-chloro-2-fluoro-5-(phenylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-4(5H)-
yl)methyl)phenyl(methoxy)carbamate (1n): 1H-NMR: δ 2.18 (s, 3H, CH3), 3.68 (s, 3H, OCH3), 3.86 (s,
3H, NOCH3), 4.95 (s, 2H, CH2), 6.78 (s, 1H, NH), 7.17-7.95 (m, 11H, ArH); EI-MS (m/z) 576 [M]+;
Anal. Calcd. for C25H23ClFN5O6S: C, 52.13; H, 4.02; N, 12.16. Found: C, 52.32; H, 4.34; N, 12.01.
methyl
2-((1-(2,4-dichloro-5-(methylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-4(5H)-
yl)methyl)phenyl(methoxy)carbamate (1o): 1H-NMR: δ 2.18 (s, 3H, CH3), 3.69 (s, 3H, OCH3), 3.84 (s,
3H, NOCH3), 4.95 (s, 2H, CH2), 7.05 (s, 1H, NH), 7.17-7.84 (m, 6H, ArH); EI-MS (m/z) 530 [M]+;
Anal. Calcd. for C20H21Cl2N5O6S: C, 45.29; H, 3.99; N, 13.20. Found: C, 45.53; H, 4.25; N, 12.94.
methyl
2-((1-(2,4-dichloro-5-(ethylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-4(5H)-
1
yl)methyl)phenyl(methoxy)carbamate (1p): H-NMR: δ 1.40 (t, 3H, J = 7.2 Hz, CH3), 2.08 (s, 3H,
CH3), 3.19 (q, 2H, J = 7.2 Hz, CH2), 3.68 (s, 3H, OCH3), 3.87 (s, 3H, NOCH3), 6.74 (s, 1H, NH), 7.17-
7.95 (m, 6H, ArH); EI-MS (m/z) 544 [M]+; Anal. Calcd. for C21H23Cl2N5O6S: C, 46.33; H, 4.26; N,
12.86.Found: C, 46.59; H, 4.62; N, 12.49.
methyl
2-((1-(2,4-dichloro-5-(phenylsulfonamido)phenyl)-3-methyl-5-oxo-1H-1,2,4-triazol-4(5H)-
yl)methyl)phenyl(methoxy)carbamate (1q): 1H-NMR: δ 2.18 (s, 3H, CH3), 3.78 (s, 3H, OCH3), 3.98 (s,
3H, NOCH3), 4.97 (s, 2H, CH2), 6.84 (s, 1H, NH), 7.17-8.02 (m, 11H, ArH); EI-MS (m/z) 592 [M]+;
Anal. Calcd. for C25H23Cl2N5O6S: C, 50.68; H, 3.91; N, 11.82. Found: C, 50.91; H, 3.97; N, 11.46.

Molecules 2010, 13
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Acknowledgements
We thank the financial support from the National Nature Science Foundation of China (No.
21002038) and the self-determined research funds of CCNU from the colleges’ basic research and
operation of MOE (No. CCNU09A01014).
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