Synthesis and insecticidal evaluation of novel anthranilic diamides containing N-substitued nitrophenylpyrazole

Article abstract of DOI:10.1016/j.bmc.2013.11.038

To cope with developing pest resistance and ecological problems associated with conventional insecticides and to search for potent insecticides targeting at ryanodine receptor (RyR), a series of novel anthranilic diamides containing N-substitued nitrophenylpyrazole were designed and synthesized. The insecticidal activities of target compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) were evaluated in our greenhouse by bio-assay tests and the relative structure-activity relationships were briefly discussed. Most compounds exhibited moderate to high activities, in which G ₇ and K₅ showed high activity against oriental armyworm and K₂ and K₄ against diamondback moth even better than the control-chlorantraniliprole. The calcium imaging technique was used to investigate the effects of several typical title compounds on the [Ca ²⁺]_i, especially the effects of G₇ on the intracellular calcium ion concentration ([Ca²⁺]_i) in neurons, which indicated that some title compounds were potent activators of the RyR.

Full text of DOI:10.1016/j.bmc.2013.11.038

Bioorganic & Medicinal Chemistry 22 (2014) 186–193
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry
journal homepage: www.elsevier.com/locate/bmc
Synthesis and insecticidal evaluation of novel anthranilic diamides
containing N-substitued nitrophenylpyrazole
Xiulan Zhang, Yuxin Li, Jinlong Ma, Hongwei Zhu, Baolei Wang, Mingzhen Mao, Lixia Xiong,
⇑
Yongqiang Li, Zhengming Li
State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
To cope with developing pest resistance and ecological problems associated with conventional insecti-
cides and to search for potent insecticides targeting at ryanodine receptor (RyR), a series of novel anthra-
nilic diamides containing N-substitued nitrophenylpyrazole were designed and synthesized. The
insecticidal activities of target compounds against oriental armyworm (Mythimna separata) and dia-
mondback moth (Plutella xylostella) were evaluated in our greenhouse by bio-assay tests and the relative
structure–activity relationships were briefly discussed. Most compounds exhibited moderate to high
activities, in which G7 and K5 showed high activity against oriental armyworm and K2 and K4 against dia-
mondback moth even better than the control-chlorantraniliprole. The calcium imaging technique was
used to investigate the effects of several typical title compounds on the [Ca2+]i, especially the effects of
G7 on the intracellular calcium ion concentration ([Ca2+]i) in neurons, which indicated that some title
compounds were potent activators of the RyR.
Received 30 September 2013
Revised 18 November 2013
Accepted 19 November 2013
Available online 27 November 2013
Keywords:
N-substitued nitrophenylpyrazole
Insecticidal activity
Calcium channel
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
Based on this reasoning, a series of novel anthranilic diamides
containing N-phenylpyrazole were designed and synthesized
Highly efficient and broad-spectra insecticides have an
important role in protecting agronomic crops and preventing dis-
ease transmission. To cope with developing pest resistance, the
discovery of new agents which act on new biochemical targets is
an important task for effective pest management.1–3 Recently,
some diamides insecticides which evoke the uncontrolled release
of calcium from calcium stores4–7 of insect RyR8 have been widely
applied in Lepidoptera pests control.9 Chlorantraniliprole10 as a
representative of the anthranilic diamides attracted considerable
attention because of its unique mode of action and good environ-
mental profiles.11–14
(Fig. 1). At first, compounds G1–8 were obtained by introducing
2-chloro-6-nitrophenyl group into pyrazole. Then compounds
K1–8 containing 2-chloro-4-nitrophenyl group were synthesized
to identify the different effect of the ortho- and para-nitro group
in phenylpyrazole moiety on insecticidal activity. To study chlorine
effect on insecticidal activity, L1–8 containing 2,4-dinitrophenyl
group in absence of chlorine were synthesized. The activities
against oriental armyworms (Mythimna separata) and diamond-
back moths (Plutella xylostella) were evaluated and the relating
structure–activity relationships were briefly discussed. To further
explore the mode of action, the effects of several typical target
compounds on [Ca2+]i in the central neurons isolated from the third
instar of beet armyworm (Spodoptera exigua) was studied by
calcium imaging technique.
In reported modifications of anthranilic diamides,15–19
N-pyridylpyrazole was preserved as a key pharmacophore. Bio-
isosterism20 has been applied in the optimization of chlorantranili-
prole in our laboratory. Considering that the high electronegativity
of nitrogen atom in pyridine in chlorantraniliprole could induce the
2. Results and discussion
2.1. Chemistry
p
electron cloud moving toward nitrogen,21,22 it was postulated that
the nitrobenzene moiety, which will be simpler to deal with and will
provide more structural variation from a synthetic standpoint,
might attain the similar activity. Thus it is worthy for us to explore
the investigation.
Chlorantraniliprole was synthesized referring to literature23 and
used as control. The intermediates 1 and 2 were prepared referring
to literature24–26 with some modification as shown in Scheme 1.
Combined ethyl trifluoroacetate with 2-acetyl furan to give inter-
mediate 1 without acidification at the end of reaction in order
to facilitate the follow-up operation, otherwise a slightly yellow
⇑
Corresponding author. Tel.: +86 22 23503732.
E-mail address: nkzml@vip.163.com (Z. Li).
0968-0896/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bmc.2013.11.038

X. Zhang et al. / Bioorg. Med. Chem. 22 (2014) 186–193
187
Scheme 2. Reagents and conditions: (i) CH3CN, KOH, TBAB, 50–60 °C; (ii) NaClO2,
KH2PO4, H2O, room temperature.
Figure 1. The strategy of title compounds’ design.
transparent liquid with diketone structure could be observed, then
underwent cyclization with NH2NH2ÁHCl yielded intermediate 2.
Subsequent reaction with corresponding substituted nitrobenzene
in the presence of 1.5 equiv of potash or sodium hydroxide
(Scheme 1) in DMF at 125 °C yielded compounds 3a–b. However,
the yield of isomers would increase if sodium hydroxide was used.
It might be due to the presence of strong base is favorable for the
transfer of charge in pyrazole ring. For the stronger electron-with-
drawing property of two nitro in 1-chloro-2,4-dinitrobenzene, 3c
can be obtained through mild substitution reaction conditions in
the presence of potash and TBATB in acetonitrile at 50–60 °C. The
crude 3a–c were used directly in the next step without further puri-
fication. The acids 4a–c (Schemes 1 and 2) were prepared by oxida-
tion of crude 3a–c with sodium chlorite rather than permanganate,
because of its favourable control, simpler processing and higher
yields, etc. And, more remarkable, no less than 11 equiv of sodium
chlorite was necessary. The key intermediates 5a–H were prepared
synthesized according to Ref. 27 as shown in Scheme 3.
Scheme 3. Reagents and conditions: (i) CH2Cl2, (COCl)2, DMF; (ii) THF, K2CO3,
reflux.
activity as we had expected. The influence of R1 in benzamide on
insecticidal activity is summarized with the sequence of C2H5,
i-C3H7, cyclopropyl, t-C4H9 P CH3 > n-C4H9 P n-C3H7 > cyclohexyl.
The larvicidal activity of target compounds against diamond-
back moth was evaluated as shown in Table 2. Most of them had
excellent larvicidal activity against diamondback moth. In
particular, compounds K2 and K4 showed 71%, 29% larvicidal
activities at the concentration of 1 Â 10À6 and 5 Â 10À7 mg LÀ1
,
2.2. Structure–activity relationship (SAR)
respectively, which were higher than the commercial chlorantra-
niliprole. The rule of target compounds’ activity against diamond-
back moth was inconsistent with oriental armyworm such as
compound K3 showed 60% death rate at 10 mg LÀ1 against oriental
armyworm but 30% at 5 Â 10À5 mg LÀ1 against diamondback moth.
The larvicidal activity of target compounds against oriental
armyworms is summarized in Table 1. The bioassay results indi-
cated that most compounds have favourable larvicidal activities
against oriental armyworm. For example, the larvicidal activities
of G5, G7, K5 and K7 against oriental armyworm at 1.0 mg L–1 were
50%, 80%, 80% and 70%, respectively. From Table 1, there is no di-
rect relationship between activities of target compounds with the
position of nitro in benzene ring, but the existence of 2-chlorine
group in benzene ring is important for the maintenance of activity.
Compared with 2,4-dinitrophenyl substitute, compounds with
2-chloro-4-nitrophenyl and 2-chloro-6-nitrophenyl substituents
showed higher insecticidal activities against oriental armyworm
2.3. Electrophysiological recordings
To determine whether these novel compounds be involved in
calcium signaling transduction, we examine the effects on the cen-
tral neurons of S. exigua on the calcium homeostasis with calcium
imaging technique after the neurons loading with fluo-3 AM.
Figure 2 shows the change of [Ca2+
] versus recording time
i
except K8. It suggests that 2-chlorine group is
a
key
when the neurons were treated with G3, G7, G8, K5, K6, K8, L6, L7
and chlorantraniliprole. The peaks of calcium concentration were
elevated to 110.51 3.27% (n = 9), 113.52 2.85% (n = 9), 107.56
3.12% (n = 9), 113.34 3.46% (n = 9), 107.02 2.18% (n = 9),
102.50 1.82% (n = 9), 103.38 2.16% (n = 9), 110.46 3.08%
(n = 9) of the initial value when the cells were treated with
1000 mg/L of G3, G7, G8, K5, K6, K8, L6, L7 and chlorantraniliprole,
pharmacophore that plays an important role on the activity and
the introduction of the nitrophenyl has positive effect on the
respectively. The recorded [Ca2+
] (F/F0) had a good positive
i
correlation with bioactivities the same as previously reported
diamides.28
To elucidate the paths that induced the change of [Ca2+]i in
neuron cells, other experiments were then applied to explore the
action mechanisms in the central neurons of S. exigua. In the
presence of extracellular calcium, the elevations of calcium ion
concentration in the neurons are higher than that in the absence
of extracellular calcium. It can be concluded that G7 could activate
the calcium channel on the plasma membrane with increasing the
intracellular Ca2+ through influx from the external and also
activate the calcium channel in the ER (endoplasmic reticulumn)
as well.
Scheme 1. Reagents and conditions: (i) EtONa, Et2O, room temperature;
(ii) NH2NH2ÁHCl, 1 M HCl/EtOH, reflux; (iii) DMF, H2O, K2CO3, 125 °C (iv) NaClO2,
KH2PO4, H2O, room temperature.

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X. Zhang et al. / Bioorg. Med. Chem. 22 (2014) 186–193
Table 1
Insecticidal activities of compounds G1–8, K1–8, L1–8 and chlorantraniliprole against oriental armyworms
Compounds
Larvicidal activity (%) at a concentration of (mg LÀ1
)
200
100
10
5
2.5
1
G1
G2
G3
G4
G5
G6
G7
G8
K1
K2
K3
K4
K5
K6
K7
K8
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
20
100
100
100
100
100
100
100
80
100
100
100
100
100
100
100
100
100
100
100
100
100
100
30
100
100
60
100
100
70
100
100
40
100
100
100
100
100
100
60
30
100
100
20
40
50
100
80
55
100
100
80
100
100
100
100
100
20
80
100
100
100
70
L1
L2
26.7
30
L3
L4
33.3
20
L5
30
L6
50
L7
L8
100
26.7
100
100
100
100
100
10
Chlorantraniliprole
100
100
100
Table 2
Insecticidal activities of compounds G1–8, K1–8, L1–8 and chlorantraniliprole against diamondback moth
Compounds
Larvicidal activity (%) at a concentration of (mgÁL-1
)
10
1
0.1
0.01
0.001
0.0001
0.00005
0.00001
0.000005
0.000001
0.0000005
G1
G2
G3
G4
G5
G6
G7
G8
K1
K2
K3
K4
K5
K6
K7
K8
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
57
100
100
100
100
100
100
100
100
100
100
100
100
100
86
100
100
100
100
100
100
100
100
100
100
100
100
57
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
86
100
100
100
100
100
100
86
57
29
100
100
100
100
100
57
100
100
100
57
43
57
29
71
100
100
100
100
30
100
100
100
86
71
71
57
29
29
71
43
100
100
L1
L2
0
L3
0
L4
71
L5
43
L6
29
L7
90
L8
0
Chlorantraniliprol
CK
100
0
100
0
100
0
100
0
100
0
100
0
100
0
86
0
29
0
0
0
Figure 3 shows the change of [Ca2+
]
i
versus recording time
G7. The elevation of calcium concentrations in the central
neurons treated with the G7 is in a concentration-dependent
manner.
Thapsigargin is the most widely used inhibitor of the ubiquitous
sarco-endoplasmic reticulum Ca2+-ATPases29 in mammalian cells.
Figure 5 shows that the depletion of intracellular calcium store
by preincubation with thapsigargin causing influence on the
response to G7, meaning that G7 could affect the activity of calcium
pump. On the other hand, Figure 5 also shows that compounds G7
and K5 could activate RyRs on the ER.
when the neurons were treated with 500 ppm G7 in the presence
or absence of extracellular calcium. Application of 500 ppm G7 to
isolated S. exigua neurons caused an increase in the cytosolic
calcium concentration. The peak of [Ca2+
] were increased to
i
105.27 2.46% (n = 27) and 103.07 2.57% (n = 27) of the initial
value after the neurons treated with 500 ppm G7 shorter than
20 s, respectively.
Figure 4 exhibits change of [Ca2+
] versus recording time
i
when the neurons were treated with different concentration of

X. Zhang et al. / Bioorg. Med. Chem. 22 (2014) 186–193
189
Figure 2. The change of [Ca2+
] versus recording time when the neurons were
i
treated with G3, G7, G8, K5, K6, K8, L6, L7 and chlorantraniliprole.
Figure 5. Effects of different concentrations of G7 and K5 on [Ca2+]i in the central
neurons of S. exigua when the neurons preincubated by different concentration of
heparin, thapsigargin. The central neurons of S. exigua third larvae were dyed by
loading with fluo-3 AM.
(M. separata) and diamondback moth (P. xylostella). In particular,
compound K2 and K4 showed 29–71% larvicidal activities against
P. xylostella at the concentration of 0.5–1 Â 10À6 mg LÀ1, which
were higher than chlorantraniliprole, and G7, K5 and K7 against
M. separata at 1.0 mg LÀ1 were 70–80%, respectively. Therefore,
the hypothesis that the introduction of nitrobenzene moiety into
chlorantraniliprole could improve the insecticidal activity is partly
supported. The calcium imaging technique was used to investigate
the effects of several typical title compounds on the [Ca2+]i, which
indicated that some title compounds were potent activators of the
RyR. The results of the present study provide useful information for
further structural optimization of these compounds and a rapid
detection for the activity of the target compounds. Further research
of anthranilic diamides containing N-substitued phenylpyrazole
are currently being undertaken in our laboratory.
Figure 3. G7 (500 ppm) induced calcium elevation in isolated S. exigua in the
presence or absence of extracellular calcium. The central neurons of S. exigua third
larvae were dyed by loading with fluo-3 AM.
4. Experimental section
4.1. Instruments
Reagents were purchased from commercial sources. Reactions
were monitored by thin-layer chromatography on silica gel
GF254 with detection by ultraviolet (UV). The melting points were
determined on an X-4 binocular microscope melting point appara-
tus (Beijing Tech Instruments Co., Beijing, China). 1H nuclear mag-
netic resonance (NMR) spectra were obtained using Bruker AV 400
and Bruker AV300 instrument in CDCl3, DMSO-d6 as solvent and
tetramethylsilane as an internal standard. Chemical shifts (d) were
given in parts per million (ppm) and were measured downfield
from internal tetramethylsilane. Elemental analyses were deter-
mined on a Yanaco CHN Corder MT-3 elemental analyzer. High
resolution mass spectrometry (HRMS) data were obtained on a
Varian QFT-ESI instrument.
Figure 4. Effects of different concentrations of G7 on [Ca2+]i in the central neurons
of S. exigua when extracellular Ca2+ was in absence (EGTA replace Ca2+). The central
neurons of S. exigua third larvae were dyed by loading with fluo-3 AM.
4.1.1. The general synthetic procedure of 3a–b
To a solution of 5-(furan-2-yl)-3-(trifluoromethyl)-1H-pyrazole
(2) (30 mmol) and K2CO3 (45 mmol) in DMF, 2 mL water was
added. The resulting mixture was heated to 50–60 °C and stirred
at room temperature for 1 h. Then the 1,2-dichloro-3-nitrobenzene
or 2-chloro-1-fluoro-4-nitrobenzene (36 mmol) in DMF was added
slowly to the mixture.30–35 The solution was heated to 125 °C for
3–4 h monitored by TLC. The mixture was concentrated in vacuo.
3. Conclusion
In conclusion, a series of novel anthranilic diamides containing
N-substitued nitrophenylpyrazole were designed and synthesized.
The bioassays showed that several compounds exhibited good to
excellent insecticidal activities against oriental armyworm

190
X. Zhang et al. / Bioorg. Med. Chem. 22 (2014) 186–193
The residue was extracted with ethyl acetate and then washed
with 1 mol LÀ1 hydrochloric acid, saturated sodium bicarbonate
solution and brine successively, dried with anhydrous magnesium
sulfate. The crude 3a–b were used directly in the next step without
further purification.
Calcd for C20H14Cl2F3N5O4: C, 46.53; H, 2.73; N, 13.57. Found: C,
46.82; H, 2.91; N, 13.27.
4.1.4.2. N-(4-Chloro-2-(ethylcarbamoyl)-6-methylphenyl)-1-(2-
chloro-6-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbox-
amide (G2). Light yellow solid, yield 61.2%, mp 172–174 °C, 1H
NMR (400 MHz, CDCl3): d 10.41 (s, 1H, Ph-NH–CO–), 8.07 (dd, 1H,
J = 8.3, 1.1 Hz, Ph-H), 7.78 (dd, 1H, J = 8.3, 1.1 Hz, Ph-H), 7.70 (s, 1H,
pyrazolyl-H), 7.59 (t, 1H, J = 8.2 Hz, Ph-H), 7.12 (s, 2H, Ph-H), 6.16
(t, 1H, J = 5.4 Hz, Ph-CO–NH–), 3.47–3.33 (m, 2H, –CH2CH3), 2.08 (s,
3H, Ph-CH3), 1.15 (t, 3H, J = 7.3 Hz, 3H, –CH2CH3). Anal. Calcd for
4.1.2. The synthetic procedure of 3c
The 5-(furan-2-yl)-3-(trifluoromethyl)-1H-pyrazole (2) (30 mmol)
was dissolved in 50 mL of acetonitrile and water, followed by the
addition of potassium hydroxide (45 mmol) and catalytic amounts
of tetrabutylammonium bromide were added. The solution was
stirred at room temperature for 1 h. Then the 1-chloro-2,4-dinitro-
benzene (36 mmol) in acetonitrile (30 mL) was added slowly to the
mixture. The solution was heated to 50–60 °C for 3–4 h monitored
by TLC. The mixture was evaporated to dryness in vacuo. The
residue was extracted with ethyl acetate and then washed with
hydrochloric acid, sodium bicarbonate solution and brine succes-
sively and dried. The crude 3c was used directly in the next step
without further purification.
C21H16Cl2F3N5O4: C, 47.56; H, 3.04; N, 13.21. Found: C, 47.48; H,
3.06; N, 12.95.
4.1.4.3. N-(4-Chloro-2-methyl-6-(propylcarbamoyl)phenyl)-1-
(2-chloro-6-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-car-
boxamide (G3). Light yellow solid, yield 57.3%, mp 190–192 °C,
1H NMR (400 MHz, CDCl3): d 10.44 (s, 1H, Ph-NH–CO–), 8.07 (dd,
1H, J = 8.3, 1.2 Hz, Ph-H), 7.78 (dd, 1H, J = 8.3, 1.2 Hz, Ph-H), 7.74 (s,
1H, pyrazolyl-H), 7.59 (t, 1H, J = 8.2 Hz, Ph-H), 7.12 (s, 2H, Ph-H),
6.17 (t, 1H, J = 5.8 Hz, Ph-CO–NH–), 3.38–3.26 (m, 2H, –CH2CH2-
CH3), 2.08 (s, 3H, Ph-CH3), 1.56–1.49 (m, 2H, –CH2CH2CH3), 0.93 (t,
3H, J = 7.4 Hz, –CH2CH2CH3). Anal. Calcd for C22H18Cl2F3N5O4: C,
48.54; H, 3.33; N, 12.87. Found: C, 47.98; H, 3.96; N, 12.47.
4.1.3. The general procedure for the compounds 4a–c
To a solution of crude 3 (30 mmol) and potassium dihydrogen
phosphate (150 mmol) in 50 mL of acetonitrile and 50 mL of water,
an aqueous solution of sodium chlorite (330 mmol) was added
dropwise under freezing. The resulting mixture was allowed to stir
overnight at room temperature. The mixture was alkalized, filtered
and the filtrate was acidized after concentrated, then extracted
with ethyl acetate. The organic extract was separated, dried, fil-
tered, concentrated and purified by silica gel chromatography to
afford main product 4a–c. Compound 4a: yield 73%, mp
151–153 °C; 1H NMR (400 MHz, CDCl3): d 10.86 (s, 1H, –COOH),
8.13 (d, 1H, J = 8.2 Hz, Ph-H), 7.85 (d, 1H, J = 8.1 Hz, Ph-H), 7.69
(t, 1H, J = 8.2 Hz, Ph-H), 7.37 (s, 1H, pyrazolyl-H). Compound 4b:
yield 72%, mp 188–190 °C; 1H NMR (400 MHz, DMSO-d6): d 14.20
(s, 1H, –COOH), 8.58 (d, 1H, J = 2.4 Hz, Ph-H), 8 .38 (dd, 1H,
J = 8.7, 2.4 Hz, Ph-H), 8.04 (d, 1H, J = 8.7 Hz, Ph-H), 7.65 (s, 1H, pyr-
azolyl-H). Compound 4c: yield 68%, mp 157–159 °C; 1H NMR
(400 MHz, CDCl3): d 9.06 (d, 1H, J = 2.4 Hz, Ph-H), 8.64 (dd, 1H,
J = 8.7, 2.4 Hz, Ph-H), 7.84 (d, 1H, J = 8.7 Hz, Ph-H), 7.43 (s, 1H, pyr-
azolyl-H).
4.1.4.4. N-(4-Chloro-2-(isopropylcarbamoyl)-6-methylphenyl)-
1-(2-chloro-6-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamide (G4).
Light yellow solid, yield 52.4%, mp 194–
196 °C, 1H NMR (400 MHz, CDCl3): d 10.39 (s, 1H, Ph-NH–CO–),
8.08 (d, 1H, J = 8.2 Hz, Ph-H), 7.79 (d, 1H, J = 8.2 Hz, Ph-H), 7.60 (t,
1H, J = 8.2 Hz, Ph-H), 7.57 (s, 1H, pyrazolyl-H), 7.18 (s, 1H, Ph-H),
7.16 (s, 1H, Ph-H), 5.93 (d, 1H, J = 7.6 Hz, Ph-CO–NH–), 4.21–4.13
(m, 1H, –CH(CH3)2), 2.11 (s, 3H, Ph-CH3), 1.98 (t, 6H, –CH(CH3)2).
Anal. Calcd for C22H18Cl2F3N5O4: C, 48.54; H, 3.33; N, 12.87. Found:
C, 48.36; H, 3.73; N, 12.54.
4.1.4.5.
N-(4-Chloro-2-(cyclopropylcarbamoyl)-6-methyl-
phenyl)-1-(2-chloro-6-nitrophenyl)-3-(trifluoromethyl)-1H-pyr-
azole-5-carboxamide (G5). Light yellow solid, yield 48.5%, mp
206–208 °C, 1H NMR (400 MHz, CDCl3): d 10.35 (s, 1H, Ph-NH–CO
–), 8.08 (d, 1H, J = 8.2 Hz, Ph-H), 7.79 (d, 1H, J = 8.2 Hz, Ph-H),
7.71 (s, 1H, pyrazolyl-H), 7.60 (t, 1H, J = 8.2 Hz, Ph-H), 7.15 (s, 1H,
Ph-H), 7.10 (s, 1H, Ph-H), 6.24 (s, 1H, Ph-CO–NH–), 2.84–2.79 (m,
1H, –CH(CH2)2), 2.10 (s, 3H, Ph-CH3), 0.91–0.83 (m, 2H, –CH(CH2)2),
0.57–0.55 (m, 2H, –CH(CH2)2). HMRS calcd for C22H16Cl2F3N5O4
([M+H]+): 542.0604, found: 542.0602.
4.1.4. The general synthetic procedure of target compounds
G1–8, K1–8, L1–8
To a solution of 4 (1 mmol) in dichloromethane (20 mL) was
added oxalyl chloride (1.5 mmol) and dimethyl-formamide
(2 drops). The solution was stirred at ambient temperature for
4 h, then concentrated in vacuo to give the crude acid chloride.
The crude acid chloride in tetrahydrofuran (10 mL) was added
slowly to a stirred solution of 5 (1.0 mmol) and triethylamine
(1.5 mmol) in tetrahydrofuran (15 mL) and refluxed for 2–3 h.36–40
Then the solution was concentrated in vacuo and diluted with
CH2Cl2 (60 mL), and washed with 1 mol LÀ1 hydrochloric acid,
saturated sodium bicarbonate solution and brine successively.
The organic extract was separated, dried, filtered, concentrated
and purified by silica gel chromatography to afford the desired title
compounds G1–8, K1–8, L1–8. The yields, melting points, 1H NMR and
elemental analysis or HRMS were listed as follows.
4.1.4.6. N-(2-(Butylcarbamoyl)-4-chloro-6-methylphenyl)-1-(2-
chloro-6-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbox-
amide (G6). Light yellow solid, yield 54.6%, mp 202–204 °C, 1H
NMR (400 MHz, CDCl3): d 10.45 (s, 1H, Ph-NH–CO–), 8.07 (d, 1H,
J = 8.2 Hz, Ph-H), 7.78 (d, 1H, J = 8.2 Hz, Ph-H), 7.72 (s, 1H,
pyrazolyl-H), 7.60 (t, 1H, J = 8.2 Hz, Ph-H), 7.12 (s, 2H, Ph-H), 6.14
(t, 1H, J = 5.2 Hz, Ph-CO–NH–), 3.38–3.33 (m, 2H, –CH2CH2CH2CH3),
2.09 (s, 3H, Ph-CH3), 1.54–1.43 (m, 2H, –CH2CH2CH2CH3), 1.41–
1.28 (m, 2H, –CH2CH2CH2CH3), 0.91 (t, 3H, J = 7.2 Hz, –CH2CH2-
CH2CH3). HMRS calcd for C23H20Cl2F3N5O4 ([M+H]+): 558.0917,
found: 558.0915.
4.1.4.1. N-(4-Chloro-2-methyl-6-(methylcarbamoyl)phenyl)-1-
(2-chloro-6-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-car-
4.1.4.7. N-(2-(tert-Butylcarbamoyl)-4-chloro-6-methylphenyl)-
1-(2-chloro-6-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamide (G7). Light yellow solid, yield 47.4%, mp
209–211 °C, 1H NMR (400 MHz, CDCl3): d 10.63 (s, 1H, Ph-NH–CO
–), 8.08 (dd, 1H, J = 8.3, 1.2 Hz, Ph-H), 7.97 (s, 1H, pyrazolyl-H),
7.79 (dd, 1H, J = 8.3, 1.2 Hz, Ph-H), 7.59 (t, 1H, J = 8.2 Hz, Ph-H),
7.03 (s, 1H, Ph-H), 7.02 (s, 1H, Ph-H), 5.92 (s, 1H, Ph-CO–NH–), 2.02
boxamide (G1).
Light yellow solid, yield 62.5%, mp 197–199 °C,
1H NMR (400 MHz, CDCl3): d 10.38 (s, 1H, Ph-NH–CO–), 8.07
(dd, 1H, J = 8.2, 1.2 Hz, Ph-H), 7.79 (dd, 1H, J = 8.2, 1.2 Hz,
Ph-H), 7.71 (s, 1H, pyrazolyl-H), 7.60 (t, 1H, J = 8.2 Hz, Ph-H), 7.14
(s, 1H, Ph-H), 7.13 (s, 1H, Ph-H), 6.17 (d, 1H, J = 4.7 Hz, Ph-CO–
NH–), 2.93 (d, 3H, J = 4.9 Hz, –NH–CH3), 2.09 (s, 3H, Ph-CH3). Anal.

X. Zhang et al. / Bioorg. Med. Chem. 22 (2014) 186–193
191
(s, 3H, Ph-CH3), 1.34 (s, 9H, –(CH3)3). Anal. Calcd for C23H20Cl2F3-
N5O4: C, 49.48; H, 3.61; N, 12.54. Found: C, 49.71; H, 4.08; N, 12.19.
Ph-H), 7.71 (d, 1H, J = 8.7 Hz, Ph-H), 7.42 (s, 1H, pyrazolyl-H), 7.27
(d, 1H, J = 2.1 Hz, Ph-H), 7.19 (d, 1H, J = 2.1 Hz, Ph-H), 6.23 (d, 1H,
J = 1.8 Hz, Ph-CO–NH–), 2.86–2.79 (m, 1H, –CH(CH2)2), 2.18 (s, 3H,
Ph-CH3), 0.93–0.88 (m, 2H, –CH(CH2)2), 0.60–0.56 (m, 2H, –
CH(CH2)2). HMRS calcd for C22H16Cl2F3N5O4 ([MÀH]À): 540.0459,
found: 540.0459.
4.1.4.8. N-(4-Chloro-2-(cyclohexylcarbamoyl)-6-methylphenyl)-
1-(2-chloro-6-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamide (G8). Light yellow solid, yield 58.2%, mp
200–202 °C, 1H NMR (400 MHz, CDCl3): d 10.38 (s, 1H, Ph-NH–CO
–), 8.08 (d, 1H, J = 8.3 Hz, Ph-H), 7.78 (d, 1H, J = 8.3 Hz, Ph-H),
7.61 (t, 1H, J = 8.2 Hz, Ph-H), 7.58 (s, 1H, pyrazolyl-H), 7.17 (s, 1H,
Ph-H), 7.14 (s, 1H, Ph-H), 5.94 (d, 1H, J = 7.6 Hz, Ph-CO–NH –),
3.89–3.81 (m, 1H, –CH(CH2)5), 2.10 (s, 3H, Ph-CH3), 1.96–1.89 (m,
2H, –CH(CH2)5, 1.77–1.64 (m, 3H, –CH(CH2)5, 1.45–1.34 (m, 2H, –
CH(CH2)5, 1.21–1.09 (m, 3H, –CH(CH2)5. Anal. Calcd for C25H22Cl2
F3N5O4: C, 51.38; H, 3.79; N, 11.98. Found: C, 51.13; H, 4.22; N,
11.78.
4.1.4.14. N-(2-(Butylcarbamoyl)-4-chloro-6-methylphenyl)-1-
(2-chloro-4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-ca
rboxamide (K6). Light yellow solid, yield 50.1%, mp 195–197 °C,
1H NMR (400 MHz, CDCl3): d 10.39 (s, 1H, Ph-NH–CO–), 8.35 (d, 1H,
J = 2.3 Hz, Ph-H), 8.27 (dd, 1H, J = 8.7, 2.3 Hz, Ph-H), 7.69 (d, 1H,
J = 8.7 Hz, Ph-H), 7.44 (s, 1H, pyrazolyl-H), 7.25 (d, 1H, J = 2.1 Hz,
Ph-H), 7.21 (d, 1H, J = 2.1 Hz, Ph-H), 6.11 (t, 1H, J = 5.7 Hz, Ph-CO–
NH–), 3.40–3.35 (m, 2H, –CH2CH2CH2CH3), 2.17 (s, 3H, Ph-CH3),
1.58–1.50 (m, 2H, –CH2CH2CH2CH3), 1.40–1.33 (m, 2H, –CH2CH2-
CH2CH3), 0.94 (t, 3H, J = 7.3 Hz, –CH2CH2CH2CH3). Anal. Calcd for
4.1.4.9. N-(4-Chloro-2-methyl-6-(methylcarbamoyl)phenyl)-1-
(2-chloro-4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamide (K1). Light yellow solid, yield 57.2%, mp
230–232 °C, 1H NMR (400 MHz, CDCl3): d 10.32 (s, 1H, Ph-NH–CO
–), 8.35 (d, 1H, J = 2.3 Hz, Ph-H), 8.27 (dd, 1H, J = 8.7, 2.3 Hz, Ph-
H), 7.71 (d, 1H, J = 8.7 Hz, Ph-H), 7.34 (s, 1H, pyrazolyl-H), 7.31 (d,
1H, J = 2.1 Hz, Ph-H), 7.28 (d, 1H, J = 2.1 Hz, Ph-H), 6.14 (q, 1H,
J = 4.6 Hz, Ph-CO–NH–), 2.98 (d, 3H, J = 4.9 Hz, –NH–CH3), 2.20 (s,
3H, Ph-CH3). HMRS calcd for C20H14Cl2F3N5O4 ([M+H]+): 516.0448,
found: 516.0446.
C23H20Cl2F3N5O4: C, 49.48; H, 3.61; N, 12.54. Found: C, 49.96; H,
4.17; N, 12.25.
4.1.4.15. N-(2-(tert-Butylcarbamoyl)-4-chloro-6-methylphenyl)-
1-(2-chloro-4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamide (K7). Light yellow solid, yield 62.4%, mp
127–129 °C, 1H NMR (400 MHz, CDCl3): d 10.51 (s, 1H, Ph-NH–CO
–), 8.35 (d, 1H, J = 2.4 Hz, Ph-H), 8.26 (dd, 1H, J = 8.7, 2.4 Hz, Ph-
H), 7.74 (s, 1H, pyrazolyl-H), 7.65 (d, 1H, J = 8.7 Hz, Ph-H), 7.11 (d,
1H, J = 2.1 Hz, Ph-H), 7.09 (d, 1H, J = 2.1 Hz, Ph-H), 5.95 (s, 1H, Ph-
CO–NH–), 2.10 (s, 3H, Ph-CH3), 1.35 (s, 9H, –(CH3)3). HMRS calcd
for C23H20Cl2F3N5O4 ([MÀH]À): 556.0772, found: 556.0770.
4.1.4.10. N-(4-Chloro-2-methyl-6-(methylcarbamoyl)phenyl)-1-
(2-chloro-4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamide (K2). Light yellow solid, yield 54.3%, mp
229–231 °C, 1H NMR (400 MHz, CDCl3): d 10.38 (s, 1H, Ph-NH–CO
–), 8.35 (d, 1H, J = 2.3 Hz, Ph-H), 8.27 (dd, 1H, J = 8.7, 2.3 Hz, Ph-
H), 7.70 (d, 1H, J = 8.7 Hz, Ph-H), 7.40 (s, 1H, pyrazolyl-H), 7.27 (d,
1H, J = 2.1 Hz, Ph-H), 7.25 (d, 1H, J = 2.1 Hz, Ph-H), 6.10 (t, 1H,
J = 5.1 Hz, Ph-CO–NH–), 3.48–3.39 (m, 2H, –CH2CH3), 2.18 (s, 3H,
Ph-CH3), 1.22 (t, 3H, J = 7.3 Hz, –CH2CH3). HMRS calcd for C21H16-
Cl2F3N5O4 ([M+H]+): 530.0604, found: 530.0601.
4.1.4.16. N-(4-Chloro-2-(cyclohexylcarbamoyl)-6-methylphenyl)-
1-(2-chloro-4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamide (K8). Light yellow solid, yield 47.5%, mp 215–
217 °C, 1H NMR (400 MHz, CDCl3): d 10.43 (s, 1H, Ph-NH–CO–),
8.34 (d, 1H, J = 2.4 Hz, Ph-H), 8.27 (dd, 1H, J = 8.7, 2.4 Hz, Ph-H),
7.69 (d, 1H, J = 8.7 Hz, Ph-H), 7.43 (s, 1H, pyrazolyl-H), 7.25 (d, 1H,
J = 2.0 Hz, Ph-H), 7.20 (d, 1H, J = 2.0 Hz, Ph-H), 5.95 (d, 1H,
J = 7.9 Hz, Ph-CO–NH –), 3.89–3.81 (m, 1H, –CH(CH2)5), 2.16
(s, 3H, Ph-CH3), 1.96–1.92 (m, 2, –CH(CH2)5), 1.78–1.74 (m, 2H, –
CH(CH2)5), 1.69–1.66 (m, 1H, –CH(CH2)5), 1.46–1.35 (m, 2H, –
CH(CH2)5), 1.24–1.13 (m, 3H, –CH(CH2)5). Anal. Calcd for C25H22-
Cl2F3N5O4: C, 51.38; H, 3.79; N, 11.98. Found: C, 51.54; H, 4.17; N,
11.68.
4.1.4.11. N-(4-Chloro-2-methyl-6-(propylcarbamoyl)phenyl)-1-
(2-chloro-4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamide (K3). Light yellow solid, yield 49.7%, mp
210–212 °C, 1H NMR (400 MHz, CDCl3): d 10.39 (s, 1H, Ph-NH–CO
–), 8.34 (d, 1H, J = 2.4 Hz, Ph-H), 8.27 (dd, 1H, J = 8.7, 2.4 Hz, Ph-
H), 7.70 (d, 1H, J = 8.7 Hz, Ph-H), 7.42 (s, 1H, pyrazolyl-H), 7.26 (d,
1H, J = 2.1 Hz, Ph-H), 7.23 (d, 1H, J = 2.1 Hz, Ph-H), 6.14 (t, 1H,
J = 5.7 Hz, Ph-CO–NH–), 3.37–3.32 (m, 2H, –CH2CH2CH3), 2.17 (s,
3H, Ph-CH3), 1.64–1.54 (m, 2H, –CH2CH2CH3), 0.96 (t, 3H,
J = 7.4 Hz, –CH2CH2CH3). HMRS calcd for C22H18Cl2F3N5O4 ([MÀH
]À): 542.0615, found: 542.0614.
4.1.4.17. N-(4-Chloro-2-methyl-6-(methylcarbamoyl)phenyl)-1-
(2,4-dinitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbox-
amide (L1). Light yellow solid, yield 60.3%, mp 204–206 °C, 1H
NMR (300 MHz, CDCl3): d 10.43 (s, 1H, Ph-NH–CO–), 8.99 (d, 1H,
J = 2.4 Hz, Ph-H), 8.58 (dd, 1H, J = 8.7, 2.4 Hz, Ph-H), 7.84 (d, 1H,
J = 8.7 Hz, Ph-H), 7.57 (s, 1H, pyrazolyl-H), 7.21 (d, 1H, J = 2.1 Hz,
Ph-H), 7.19 (d, 1H, J = 2.1 Hz, Ph-H), 6.10 (q, 1H, J = 4.6 Hz, Ph-CO–
NH–), 2.99 (d, 3H, J = 4.9 Hz, –NH–CH3), 2.08 (s, 3H, Ph-CH3). HMRS
calcd for C20H14ClF3N6O6 ([M+H]+): 527.0688, found: 527.0686.
4.1.4.12. N-(4-Chloro-2-(isopropylcarbamoyl)-6-methylphenyl)-
1-(2-chloro-4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-
carboxamide (K4). Light yellow solid, yield 52.6%, mp
213–215 °C, 1H NMR (400 MHz, CDCl3): d 10.46 (s, 1H, Ph-NH–CO
–), 8.34 (d, 1H, J = 2.3 Hz, Ph-H), 8.26 (dd, 1H, J = 8.7, 2.3 Hz, Ph-
H), 7.68 (d, 1H, J = 8.7 Hz, Ph-H), 7.51 (s, 1H, pyrazolyl-H), 7.21 (d,
1H, J = 2.1 Hz, Ph-H), 7.17 (d, 1H, J = 2.1 Hz, Ph-H), 5.93 (d, 1H,
J = 7.7 Hz, Ph-CO–NH–), 4.21–4.08 (m, 1H, –CH(CH3)2), 2.14 (s, 3H,
Ph-CH3), 1.20 (d, 6H, J = 6.5 Hz, –CH(CH3)2). HMRS calcd for
C22H18Cl2F3N5O4 ([M+H]+): 544.0761, found: 544.0755.
4.1.4.18. N-(4-Chloro-2-(ethylcarbamoyl)-6-methylphenyl)-1-
(2,4-dinitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbox-
amide (L2). Light yellow solid, yield 54.6%, mp 163–165 °C, 1H
NMR (400 MHz, CDCl3): d 10.47 (s, 1H, Ph-NH–CO–), 8.99 (d, 1H,
J = 2.4 Hz, Ph-H), 8.58 (dd, 1H, J = 8.7, 2.4 Hz, Ph-H), 7.83 (d, 1H,
J = 8.7 Hz, Ph-H), 7.54 (s, 1H, pyrazolyl-H), 7.22 (d, 1H, J = 2.1 Hz,
Ph-H), 7.20 (d, 1H, J = 2.1 Hz, Ph-H), 6.07 (t, 1H, J = 5.3 Hz, Ph-
CO–NH–), 3.50–3.40 (m, 2H, –CH2CH3), 2.09 (s, 3H, Ph-CH3), 1.21
(t, 3H, J = 7.3 Hz, –CH2CH3). HMRS calcd for C21H16ClF3N6O6
([M+Na]+): 563.0664, found: 563.0660.
4.1.4.13.
N-(4-Chloro-2-(cyclopropylcarbamoyl)-6-methyl-
phenyl)-1-(2-chloro-4-nitrophenyl)-3-(trifluoromethyl)-1H-pyr
azole-5-carboxamide (K5). Light yellow solid, yield 61.2%, mp
217–219 °C, 1H NMR (400 MHz, CDCl3): d 10.35 (s, 1H, Ph-NH–CO
–), 8.35 (d, 1H, J = 2.3 Hz, Ph-H), 8.27 (dd, 1H, J = 8.7, 2.3 Hz,

192
X. Zhang et al. / Bioorg. Med. Chem. 22 (2014) 186–193
4.1.4.19. N-(4-Chloro-2-methyl-6-(propylcarbamoyl)phenyl)-1-
(2,4-dinitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbox-
amide (L3). Light yellow solid, yield 51.2%, mp 136–138 °C, 1H
NMR (400 MHz, CDCl3): d 10.49 (s, 1H, Ph-NH–CO–), 8.99 (d, 1H,
J = 2.4 Hz, Ph-H), 8.58 (dd, 1H, J = 8.7, 2.4 Hz, Ph-H), 7.83 (d, 1H,
J = 8.7 Hz, Ph-H), 7.60 (s, 1H, pyrazolyl-H), 7.20 (d, 1H, J = 2.1 Hz,
Ph-H), 7.17 (d, 1H, J = 2.1 Hz, Ph-H), 6.10 (t, 1H, J = 5.7 Hz, Ph-CO–
NH–), 3.39–3.34 (m, 2H, –CH2CH2CH3), 2.07 (s, 3H, Ph-CH3), 1.63–
1.52 (m, 2H, –CH2CH2CH3), 0.95 (t, 3H, J = 7.4 Hz, 2H, –CH2CH2-
CH3). HMRS calcd for C22H18ClF3N6O6 ([M+Na]+): 577.0821, found:
577.0825.
2H, –CH(CH2)5), 1.69–1.65 (m, 1H, –CH(CH2)5), 1.45–1.36 (m, 2H,
–CH(CH2)5), 1.24–1.17 (m, 3H, –CH(CH2)5). HMRS calcd for C25H22-
ClF3N6O6 ([M+Na]+): 617.1134, found: 617.1137.
4.2. Biological assay and calcium imaging
Insecticidal activities against oriental armyworms (M. separata)
and diamondback moths (P. xylostella) were performed in our
greenhouse. The bioassay was replicated at 25 1 °C according to
statistical requirements. Assessments were made on a dead/alive
basis, and mortality rates were corrected applying Abbott’s for-
mula.41 Evaluation was based on a percentage scale of 0–100,
where 0 equals no activity, and 100 equals total kill. Error of the
experiments was 5%. For comparative purposes, chlorantraniliprole
was treated as a control under the same conditions.
The insecticidal activities of compounds G1–8, K1–8, L1–8 and chl-
orantraniliprole against oriental armyworm (M. separata) were
evaluated by using the reported procedure.42 For the foliar tests,
individual corn leaves were placed on moistened pieces of filter pa-
per in Petri dishes. The leaves were then sprayed with the test
solution and allowed to dry. The dishes were infested with 10
fourth-instar oriental armyworm larvae. Percentage mortalities
were evaluated 2 days after treatment. Each treatment was per-
formed three times.
4.1.4.20. N-(4-Chloro-2-(isopropylcarbamoyl)-6-methylphenyl)-
1-(2,4-dinitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-car-
boxamide (L4). Light yellow solid, yield 61.4%, mp 143–145 °C,
1H NMR (400 MHz, CDCl3): d 10.49 (s, 1H, Ph-NH–CO–), 9.00 (d, 1H,
J = 2.4 Hz, Ph-H), 8.59 (dd, 1H, J = 8.7, 2.4 Hz, Ph-H), 7.83 (d,
J = 8.7 Hz), 7.47 (s, 1H, pyrazolyl-H), 7.25 (d, 1H, J = 2.1 Hz, Ph-H),
7.20 (d, 1H, J = 2.1 Hz, Ph-H), 5.90 (d, 1H, J = 7.7 Hz, Ph-CO–NH–),
4.24–4.13 (m, 1H, –CH(CH3)2), 2.11 (s, 3H, Ph-CH3), 1.22 (d, 6H,
J = 6.5 Hz, -CH(CH3)2). HMRS calcd for C22H18ClF3N6O6 ([M+Na]+):
577.0821, found: 577.0822.
4.1.4.21.
N-(4-Chloro-2-(cyclopropylcarbamoyl)-6-methyl-
The larvicidal activity of compounds G1–8, K1–8, L1–8 and chlo-
rantraniliprole against diamondback moth (P. xylostella) was tested
by the leaf disc method. At first, a solution of each test sample in
DMF (AR, purchased from Alfa Aesar) at a concentration of
200 mg/L was prepared and then diluted to the required concen-
tration with water (distilled). Leaf disks (6 cm  2 cm) were cut
from fresh cabbage leaves and then were sprayed with the test
solution for 3 s and allowed to dry. The resulting leaf disks were
placed individually into glass tubes. Each disk was infested with
thirty second-instar diamondback moth larvae. Percentage mortal-
ities were evaluated 2 days after treatment. Each treatment was
performed three times.
phenyl)-1-(2,4-dinitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-
5-carboxamide (L5). Light yellow solid, yield 49.8%, mp
191–193 °C, 1H NMR (400 MHz, CDCl3): d 10.47 (s, 1H, Ph-NH–CO
–), 9.03 (d, 1H, J = 2.3 Hz, Ph-H), 8.62 (dd, 1H, J = 8.6, 2.3 Hz, Ph-
H), 7.87 (d, 1H, J = 8.7 Hz, Ph-H), 7.63 (s, 1H, pyrazolyl-H), 7.24 (d,
1H, J = 2.1 Hz, Ph-H), 7.16 (d, 1H, J = 2.1 Hz, Ph-H), 6.26 (d, 1H, J =
1.2 Hz, Ph-CO–NH–), 2.88–2.83 (m, 1H, –CH(CH2)2), 2.11 (s, 3H, Ph-
CH3), 0.94–0.88 (m, 2H, –CH(CH2)2), 0.63–0.58 (m, 2H, –CH(CH2)2).
HMRS calcd for
575.0668.
C
22H16ClF3N6O6 ([M+Na]+): 575.0664, found:
4.1.4.22. N-(2-(Butylcarbamoyl)-4-chloro-6-methylphenyl)-1-
(2,4-dinitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbox-
The effect of some novel compounds on the calcium concentra-
tion was evaluated by using the reported methods.28
amide (L6).
Light yellow solid, yield 46.5%, mp 109–111 °C, 1H
NMR (400 MHz, CDCl3): d 10.48 (s, 1H, Ph-NH–CO–), 9.00 (d, 1H,
J = 2.4 Hz, Ph-H), 8.58 (dd, 1H, J = 8.7, 2.4 Hz, Ph-H), 7.83 (d, 1H,
J = 8.7 Hz, Ph-H), 7.57 (s, 1H, pyrazolyl-H), 7.21 (d, J = 2.1 Hz),
7.18 (d, J = 2.1 Hz), 6.06 (t, 1H, J = 5.7 Hz, Ph-CO–NH–), 3.43–3.38
(m, 2H, –CH2CH2CH2CH3), 2.09 (s, 3H, Ph-CH3), 1.59–1.49 (m, 2H,
–CH2CH2CH2CH3), 1.41–1.32 (m, 2H, –CH2CH2CH2CH3), 0.93 (t,
3H, J = 7.3 Hz, –CH2CH2CH2CH3). HMRS calcd for C23H20ClF3N6O6
([M+H]+): 569.1158, found: 569.1149.
Acknowledgments
The project was supported by the National Basic Research Pro-
gram of China (973 project 2010CB126106), Specialized Research
Fund for the Doctorial Program of Higher Education
(20110031110017), Natural Science Foundation of China (No.
31370039), the National Key Technologies R&D Program
(2011BAE06B05) and the Tianjin Natural Science Foundation, Chi-
na (No. 11JCYBJC08600).
4.1.4.23. N-(2-(tert-Butylcarbamoyl)-4-chloro-6-methylphenyl)-
1-(2,4-dinitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-car-
boxamide (L7). Light yellow solid, yield 57.3%, mp 164–166 °C,
1H NMR (400 MHz, CDCl3): d 10.55 (s, 1H, Ph-NH–CO–), 9.00 (d, 1H,
J = 2.4 Hz, Ph-H), 8.58 (dd, 1H, J = 8.7, 2.4 Hz, Ph-H), 7.81 (d, 1H,
J = 8.7 Hz, Ph-H), 7.75 (s, 1H, pyrazolyl-H), 7.12 (d, 1H, J = 2.1 Hz,
Ph-H), 7.09 (d, 1H, J = 2.1 Hz, Ph-H), 5.87 (s, 1H, Ph-CO–NH–), 2.04
(s, 3H, Ph-CH3), 1.35 (s, 9H, –(CH3)3). Anal. Calcd for C23H20ClF3-
N6O6: C, 48.56; H, 3.54; N, 14.77. Found: C, 48.64; H, 3.98; N, 14.31.
References and notes
1. Srivastava, C. N.; Mohan, L.; Sharma, P.; Maurya, P. J. Entomol. Res. 2011, 35,
255.
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