Synthesis and insecticidal evaluation of novel phthalic diamides containing 1,2,3-triazoles via click reaction

Article abstract of DOI:10.1002/cjoc.201400202

A series of novel phthalic diamide derivatives containing 1,2,3-triazole moiety were synthesized using one-pot click chemistry approach and characterized by ¹H NMR and HRMS. The insecticidal activity against armyworm (Mythimna separata), Tetranychu scinnabarinus and cowpea aphid (Aphis craccivora) was evaluated. Compounds 4II-a and 4II-i showed 50% insecticidal activity against armyworm (Mythimna separata) at the concentration of 4 mg/L and one-third of the compounds had moderate activity against Tetranychus cinnabarinus at 500 mg/L. Copyright

Full text of DOI:10.1002/cjoc.201400202

FULL PAPER
DOI: 10.1002/cjoc.201400202
Synthesis and Insecticidal Evaluation of Novel Phthalic
Diamides Containing 1,2,3-Triazoles via Click Reaction
Yinbo Chen, Youxin Xiao, Xusheng Shao, Xiaoyong Xu, and Zhong Li*
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science
and Technology, Shanghai 200237, China
A series of novel phthalic diamide derivatives containing 1,2,3-triazole moiety were synthesized using one-pot
1
click chemistry approach and characterized by H NMR and HRMS. The insecticidal activity against armyworm
(Mythimna separata), Tetranychus cinnabarinus and cowpea aphid (Aphis craccivora) was evaluated. Compounds
4II-a and 4II-i showed 50% insecticidal activity against armyworm (Mythimna separata) at the concentration of 4
mg/L and one-third of the compounds had moderate activity against Tetranychus cinnabarinus at 500 mg/L.
Keywords phthalic diamide, 1,2,3-triazole, click chemistry, synthesis, bioactivity
Introduction
1,2,3-Triazoles are considered privileged structures
in medicinal chemistry and also serve as versatile
building blocks for the construction of novel potent
compounds.[10-16] 1,2,3-Triazoles conjugated with a
wide range of heterocyclic moieties exhibited potent
biological properties including insecticidal,[17-19] anti-
fungal,[20] anti-HIV,[ 21] antimicrobial[22] and antibacte-
rial[23] activity. The promising biological diversity of
1,2,3-triazole scaffold urges us to synthesize and bio-
logically evaluate a series of novel structural variants of
phthalic diamide derivatives.
In the past decade, the diamides, as the newest major
class of insecticides, have attracted considerable atten-
tion and inaugurated the new era of synthetic insecti-
cides.[1-3] However, with the increase of the diamides
used on the crop protection, the problems of resistance
and cross-resistance have received much attention,[4]
which call for the discovery and development of newer
and more potent leading compounds in pest manage-
ment.
Developed by Bayer Crop Science and Nihon
Nohyaku in 2007, Flubendiamide became the first
commercialized phthalic diamide insecticides targeting
insect ryanodine receptors (RyRs) and was character-
ized by its extremely high intrinsic potency, remarkable
selectivity, low ecotoxicity and broad insecticidal spec-
tra.[5,6] Structurally, phthalic diamide derivatives can be
categorized into three parts as shown in Figure 1: (A)
the phthaloyl moiety, (B) the aliphatic amide moiety
and (C) the aromatic amide moiety. In previous studies,
modifications related to part (B) had a significant im-
pact on the insecticidal activity,[7-9] which encouraged
us to explore further improvement by structural modifi-
cations.
Moreover, the click chemistry based one-pot synthe-
sis of 1,2,3-triazoles starting from anilines was recently
used that avoided the isolation of the explosive aryl
azides.[24,25] This procedure offered advantages in terms
of safety, ease of execution, and efficiency. Therefore,
this synthetic methodology was selected to initiate in
this study.
Enlightened by all of intriguing reasons above, a se-
ries of novel phthalic diamide-1,2,3-triazole hybrids
were designed and synthesized by one-pot click reaction
(Figure 2). The insecticidal activity against armyworm
(Mythimna separata), Tetranychus cinnabarinus and
cowpea aphid (Aphis craccivora) was evaluated.
Results and Discussion
R1
O
Synthesis
X
N R2
B
C
The reaction sequence employed for the synthesis of
the title compounds 4I－4II was shown in Scheme 1.
The 3-iodophthalic anhydride and compounds 2I－2II
were synthesized in high yields by referring to the
known procedure.[26,27] In the presence of trifluoroacetic
N
Ar
A
O
R3
Figure 1 General formula of phthalic diamides.
*
E-mail: lizhong@ecust.edu.cn; Tel.: 0086-021-64253540; Fax: 0086-021-64252603
Received April 1, 2014; accepted May 3, 2014; published online June 13, 2014.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201400202 or from the author.
592
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Chin. J. Chem. 2014, 32, 592—598

Synthesis and Insecticidal Evaluation of Novel Phthalic Diamides Containing 1,2,3-Triazoles
directly at room temperature without any workup pro-
cedure. The target compounds 4I were obtained in
moderate to high yields due to the substituents Y.
2-Position substituents decreased the yields and the
electron-withdrawing groups increased reaction yields,
which indicated that the steric effect and electronic ef-
fect affected the yields. For example, with the OMe
group at 2-position, compound 4I-i was 30% yield.
Otherwise, compound 4I-d with NO2 group at 4-posi-
tion was 80% yield. Unexpectedly, the same procedure
to prepare the target compounds 4II failed due to in-
solubility of the intermediate 3II in CH3CN. When ethyl
acetate was added into the second reaction to help dis-
solve 3II, it reacted smoothly to afford the desired
products in high yields.
Initially, we investigated the effect of catalysts on
this click reaction. CuSO4-sodium ascorbate, which was
usually used to catalyze the click reaction, had no cata-
lytic effect on the reaction. However, the catalyst of CuI
could make it. Generally, the amount of the copper salt
played a particularly important role in the click reaction.
But, the key to synthesis of desired compounds in high
yields was the amount of Et3N. Firstly, we commenced
our study using 0.1 equiv. Et3N and got no target com-
pound except by-product. When the amount of Et3N
was decreased from 1.0 equiv. to 0.3 equiv., the mixture
of target compound and by-product was obtained. Fi-
nally, 0.2 equiv. Et3N exhibited the highest yields with-
out the by-product.
O
O
R
R
S
I
HN
HN
I
HN
N
N
N
Y
O
O
O
O
X
N
HN
N
N
CF3
F
CF3
F
CF3
CF3
Y
Flubendiamide
Figure 2 Molecular design of 1,2,3-triazole-modified phthalic
diamides.
Scheme 1 General synthetic route for title compounds
R R
HN
R R
H2N
I
I
O
O
O
TFAA
O
CH3CN
Toluene
O
OH
2I-2II
1
R R
CF3
F
CF3
I
HN
H2N
O
O
TFA, CH CN
3
HN
CF3
F
CF3
3I-3II
Insecticidal activity
The activity against armyworm was summarized in
Table 1. All of the prepared compounds were initially
tested at the concentration of 500 mg/L, and conse-
quently the compounds with high insecticidal potency
were investigated further at lower concentration. The
preliminary bioassays indicated that most compounds
had favorable insecticidal activity against armyworm at
500 mg/L. Especially, compounds 4II-a and 4II-i ex-
hibited 50% larvicidal activity at the concentration of 4
mg/L. The target compounds containing R＝H (4I)
caused a large drop in potency compared with counter-
parts containing R＝CH3 (4II), which suggested that the
introduction of dimethyl group into the aliphatic amide
moiety had a positive effect on the activity. Among
monosubstituted derivatives, compared to nonsubsti-
tuted compounds (4I-a and 4II-a), substituents did not
improve the activity except for compound 4I-c. Among
multisubstituted compounds, the compounds 4I-j, 4I-m,
4II-d and 4II-i with the existence of 2-F-3-Br and
2-Br-6-F groups showed relatively higher mortality. For
the effect of substituted position, it was observed that
the substitutions at 2-position decreased the activity
(e.g., 4I-h and 4I-i). On the whole, introducing electron-
withdrawing groups, electron-donating groups, or halo-
gen atoms at different positions did not contribute to
great improvement of the bioactivity compared with
4I-a and 4II-a.
NH2
N3
t-BuONO, TMSN3
CH3CN
3I-3II
+
Y
Y
R R
N
I
HN
N
N
Et N
CuI,
O
O
3
Y
HN
CF3
F
CF3
4I-4II
I: R = H; II: R = CH3
anhydride, compounds 2I－2II were first transformed
to corresponding N-substituted isoimides and subse-
quently reacted with 4-heptafluoroisopropyl-2-methyl-
aniline catalyzed by trifluoroacetic acid to give the key
intermediates 3I－3II.
In the final step, a wide range of anilines were dis-
solved in acetonitrile and reacted in the presence of
t-BuONO and TMSN3 at 0 ℃, with warming to room
temperature. After complete consumption of starting
material, catalytic amounts of CuI (0.4 equiv.), Et3N
(0.2 equiv.) and compound 3I (1.0 equiv.) were added
Chin. J. Chem. 2014, 32, 592—598
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Chen et al.
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Table 1 Insecticidal activity data of the title compounds 4I－4II
Mythimna separata
Tetranychus cinnabarinus
No Compound
R
Y
500 mg/L
80
100 mg/L
nt a
nt
20 mg/L
nt
4 mg/L
nt
500 mg/L
100 mg/L
1
2
3
4
5
6
7
8
9
4I-a
4I-b
4I-c
4I-d
4I-e
4I-f
4I-g
4I-h
4I-i
H
H
100
80
80
80
0
0
H
4-Me
80
nt
nt
0
H
4-Cl
100
80
30
nt
nt
0
H
4-NO2
nt
nt
nt
0
H
3-F
80
nt
nt
nt
nt
0
H
3-CF3
0
nt
nt
nt
80
80
0
H
3-Me
80
nt
nt
nt
50
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
nt
100
H
2-F
0
nt
nt
nt
H
2-OMe
2-F-3-Br
2-Br-4-CF3
3-F-4-OMe
2-Br-6-F
4-Br-2,5-2F
2,6-2F-4-I
H
0
nt
nt
nt
0
10 4I-j
H
100
0
0
nt
nt
0
11 4I-k
H
nt
nt
nt
0
12 4I-l
H
80
nt
nt
nt
0
13 4I-m
H
100
80
0
nt
nt
0
14 4I-n
H
nt
nt
nt
0
15 4I-o
H
80
70
nt
nt
0
16 4II-a
17 4II-b
18 4II-c
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
－
－
100
100
100
100
80
100
80
70
0
50
nt
50
0
3-CF3
4-CF3
100
100
80
20
70
50
0
nt
0
19 4II-d
20 4II-e
2-F-3-Br
2-Br-4-CF3
3-F-4-OMe
4-Br-2,5-2F
2,6-2F-4-I
2-Br-6-F
－
40
nt
0
0
21 4II-f
100
0
30
nt
60
0
22 4II-g
23 4II-h
24 4II-i
nt
nt
nt
100
100
100
100
100
100
100
100
80
80
100
100
0
0
50
100
100
0
25 Flubendiamide
26 Avermectin
a nt＝not tested.
nt
100
－
The activity against Tetranychu scinnabarinus was
also evaluated as shown in Table 1. The results indi-
cated that one-third of the synthesized compounds had
moderate to high activity against Tetranychus cinna-
barinus at the concentration of 500 mg/L. Moreover,
compound 4I-g showed 50% insecticidal activity at 100
mg/L. This suggested that activity varied significantly
depending on the types and patterns of the substituents.
The activity of target compounds against cowpea
aphid (Aphis craccivora) was also tested. All of the tar-
get compounds showed no activity as we had expected.
the title compounds against Tetranychus cinnabarinus
was also evaluated; activity was significantly influenced
by the substituents. The current results of the target
compounds provide useful information and further
structural optimization is in progress in our laboratory.
Experimental
Biological assay
All bioassays were performed on representative test
organisms reared in the laboratory. The bioassay was
repeated at (25±1) ℃ according to statistical re-
quirements. All of the compounds were dissolved in
N,N-dimethylformamide and diluted with distilled water
containing Triton X-100 (0.1 mg/L) to obtain four con-
centrations. For comparative purposes, Flubendiamide
and Avermectin as control were tested under the same
conditions.
Conclusions
In conclusion, a series of 1,2,3-trizole moiety modi-
fied phthalic diamide derivatives were synthesized using
one-pot click reaction and their structures were charac-
1
terized by H NMR and HRMS. The bioassays show
that most of the compounds exhibit favorable activity
against armyworm (Mythimna separata). Exhilaratingly,
compounds 4II-a and 4II-I exhibit 50% insecticidal
activity at 4 mg/L. Moreover, the insecticidal activity of
Insecticidal test for armyworm (Mythimna sepatara):
The insecticidal activity against armyworm was tested
by foliar application. Individual corn (Zea mays) leaves
were placed on moistened pieces of filter paper in Petri
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Chin. J. Chem. 2014, 32, 592—598

Synthesis and Insecticidal Evaluation of Novel Phthalic Diamides Containing 1,2,3-Triazoles
dishes. The leaves were then sprayed with the com-
pounds solution and exposed to dry. The dishes were
infested with 10 third-instar larvae and placed in the
conditioned room. The mortality rates were evaluated
48 h after treatment. Each treatment had three repeti-
tions and the data were adjusted and subjected to probit
analysis as before.
NMR (400 MHz, DMSO-d6) δ: 13.21 (s, 1H), 8.66 (t,
J＝5.2 Hz, 1H), 8.08 (d, J＝8.0 Hz, 1H), 7.91 (d, J＝
8.0 Hz, 1H), 7.25 (t, J＝8.0 Hz, 1H), 3.99 (dd, J＝5.2,
2.4 Hz, 2H), 3.12 (t, J＝2.4 Hz, 1H).
3-Iodo-2-((2-methylbut-3-yn-2-yl)carbamoyl)ben-
zoic acid 2II White solid, yield 70%; m.p. 182－185
1
℃; H NMR (400 MHz, DMSO-d6) δ: 13.13 (s, 1H),
Insecticidal test for Tetranychus cinnabarinus: Cut
round sections from chemically untreated broad bean
leaves. Leaves must be in good condition. Collect about
40 adult mites with the fine pointed brush onto each leaf
section. The leaf disc with mites was placed under the
Potter spray tower, and then sprayed with test liquids
(pressure 5 Ib/iW2). The test set with the highest con-
centrations of organic solvents Tween water was as a
blank control. The leaf discs with mite are air dried and
placed at a room with temperature of 24－26 ℃, pho-
toperiod 14 h. Using hand lens assesses mortality after
48 h by checking each mite’s ability to show movement
in response to a touch with a small brush. Express re-
sults as percentage mortality and correct for untreated
mortality using Abbott’s formula. Each process was
repeated for 3 times.
Insecticidal test for cowpea aphid (Aphis craccivora):
The activity of the compounds against cowpea aphid
was tested by leaf-dip method. The leaves of the horse-
bean plant with 40－60 apterous adults were dipped in
diluted solutions of the chemicals containing Triton
X-100 (0.1 mg•L−1) for 5 s and the excess solution was
sucked out with filter paper, and the burgeons were
placed in the conditioned room ((25±1) ℃, 50% RH).
Water containing Triton X-100 (0.1 mg•L−1) was used
as a control. The mortality rates were evaluated 24 h
after treatment. Each treatment had three repetitions and
the data were adjusted and subjected to probit analysis
as before.
8.32 (s, 1H), 8.05 (dd, J＝8.0, 0.8 Hz, 1H), 7.87 (dd,
J＝8.0, 0.8 Hz, 1H), 7.21 (t, J＝8.0 Hz, 1H), 3.10 (s,
1H), 1.60 (s, 6H).
General procedure for the synthesis of 3I－3II
Trifluoroacetic anhydride (1.575 g, 7.5 mmol) was
added to a suspension of compound 2I－2II (5.0 mmol)
in toluene (20 mL) and the reaction mixture was stirred
at room temperature for 30 min. The solvent was re-
moved under reduced pressure to obtain a product in a
crude form quantitatively, which was used in the sub-
sequent reaction without purification. 2-Methyl-4-(per-
fluoropropan-2-yl)aniline (1.375 g, 5.0 mmol) and
trifluoroacetic acid (0.05 g) were added to a solution of
above product dissolved in acetonitrile (20 mL). The
reaction mixture was stirred for an additional hour under
ice bath and then allowed to warm to room temperature.
The progress of the reaction was followed by TLC. Af-
ter the completion of reaction, the solvent was removed
under reduced pressure, and the residue was purified by
silica gel column chromatography (ethyl acetate ∶
petroleum ether＝4∶1, volume ratio) to afford the tar-
get compounds 3I－3II.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(prop-2-yn-1-yl)phthalamide 3I White
1
powder, yield 60%; m.p. 176－179 ℃; H NMR (400
MHz, DMSO-d6) δ: 9.81 (s, 1H), 8.82 (t, J＝5.2 Hz,
1H), 8.03 (d, J＝8.0 Hz, 1H), 7.77 (d, J＝8.0 Hz, 1H),
7.73 (d, J＝7.6 Hz, 1H), 7.53－7.51 (m, 2H), 7.30 (t,
J＝8.0 Hz, 1H), 3.98 (dd, J＝5.2, 2.4 Hz, 2H), 3.00 (t,
J＝2.4 Hz, 1H), 2.35 (s, 3H).
Analytical instruments
All melting points (m.p.) were observed on Büchi
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(2-methylbut-3-yn-2-yl)phthalamide 3II
White powder, yield 65%; m.p. 212－214 ℃; 1H NMR
(400 MHz, DMSO-d6) δ: 9.64 (s, 1H), 8.55 (s, 1H), 8.01
(d, J＝8.0 Hz, 1H), 7.91 (d, J＝8.0 Hz, 1H), 7.68 (d,
J＝7.6 Hz, 1H), 7.53－7.51 (m, 2H), 7.27 (t, J＝8.0 Hz,
1H), 2.93 (s, 1H), 2.37 (s, 3H), 1.52 (s, 6H).
1
Melting Point B540 and uncorrected. H NMR spectra
were recorded on a Bruker AM-400 (400 MHz) spec-
trometer with DMSO-d6 as the solvent and TMS as the
internal standard. High-resolution mass spectra were
recorded under electron impact (70 eV) condition using
a MicroMass GCT CA 055 instrument. Analytical
thin-layer chromatography (TLC) was carried out on
precoated plates (silica gel 60 F254), and spots were
visualized with ultraviolet (UV) light.
General procedure for the synthesis of 4I
Different aniline (0.5 mmol) was dissolved in
CH3CN (15 mL) in a 25 mL round-bottomed flask and
cooled to 0 ℃ in an ice bath. To this stirred mixture
was added t-BuONO (78 mg, 0.75 mmol) followed by
TMSN3 (69 mg, 0.6 mmol) dropwise. The resulting so-
lution was stirred at room temperature for 2 h. Com-
pound 3I (205 mg, 0.35 mmol), CuI (27 mg, 0.14 mmol)
and Et3N (8 mg, 0.07 mmol) were then added and the
reaction was stirred at room temperature. The progress
of the reaction was monitored by TLC. After the com-
pletion of reaction, the solvent was removed under re-
duced pressure, and the residue was purified by silica
General procedure for the synthesis of 2I－2II
A solution of aliphatic amines (11.0 mmol) in ace-
tonitrile (5 mL) was slowly added to a suspension of
3-iodophthalic anhydride (2.74 g, 10.0 mmol) in ace-
tonitrile (15 mL). The reaction mixture was stirred at
room temperature and monitored by TLC. After com-
pletion, the precipitate was collected by filtration and
washed with a small amount of cold acetonitrile.
3-Iodo-2-(prop-2-yn-1-ylcarbamoyl)benzoic acid
1
2I White solid, yield 70%; m.p. 208－211 ℃; H
Chin. J. Chem. 2014, 32, 592—598
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595

Chen et al.
FULL PAPER
gel column chromatography using petroleum ether/ethyl
acetate as the eluting solution to afford the target com-
pounds 4I.
DMSO-d6) δ: 9.97 (s, 1H), 9.12 (t, J＝5.6 Hz, 1H), 8.77
(s, 1H), 8.14 (s, 1H), 8.10－8.05 (m, 2H), 7.84 (d, J＝
8.0 Hz, 1H), 7.80－7.74 (m, 2H), 7.54 (d, J＝8.4 Hz,
1H), 7.42 (s, 1H), 7.32 (t, J＝8.0 Hz, 1H), 7.19 (d, J＝
8.4 Hz, 1H), 4.57 (d, J＝5.6 Hz, 2H), 2.30 (s, 3H).
HRMS (ES＋) calcd for C28H19N5O2F10I [M＋H]＋:
774.0424, found 774.0428.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-
phthalamide 4I-a White powder, yield 70%; m.p.
110－113 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 10.01
(s, 1H), 9.08 (t, J＝5.6 Hz, 1H), 8.63 (s, 1H), 8.06 (dd,
J＝8.0, 0.8 Hz, 1H), 7.78－7.74 (m, 3H), 7.63 (d, J＝
8.0 Hz, 1H), 7.53－7.44 (m, 4H), 7.35－7.30 (m, 2H),
4.55 (d, J＝5.6 Hz, 2H), 2.33 (s, 3H). HRMS (ES＋)
calcd for C27H19N5O2F7INa [M＋Na]＋: 728.0369, found
728.0358.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(m-tolyl)-1H-1,2,3-triazol-4-yl)meth-
yl)phthalamide 4I-g White powder, yield 45%; m.p.
116－119 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 10.00
(s, 1H), 9.07 (t, J＝5.6 Hz, 1H), 8.61 (s, 1H), 8.06 (d,
J＝8.0 Hz, 1H), 7.76 (d, J＝7.6 Hz, 1H), 7.64 (s, 1H),
7.61 (d, J＝8.8 Hz, 1H), 7.53－7.49 (m, 2H), 7.38 (t,
J＝8.0 Hz, 1H), 7.34－7.27 (m, 3H), 4.55 (d, J＝5.6 Hz,
2H), 2.36 (s, 3H), 2.33 (s, 3H); HRMS (ES＋) calcd for
C28H22N5O2F7I [M＋H]＋: 720.0706, found 720.0701.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(2-fluorophenyl)-1H-1,2,3-triazol-4-
yl)-methyl)phthalamide 4I-h White powder, yield
62%; m.p. 172 － 174 ℃ ; 1H NMR (400 MHz,
DMSO-d6) δ: 9.97 (s, 1H), 9.09 (t, J＝5.6 Hz, 1H), 8.48
(d, J＝2.0 Hz, 1H), 8.06 (d, J＝8.0 Hz, 1H), 7.81－7.76
(m, 2H), 7.64－7.57 (m, 2H), 7.53－7.49 (m, 2H), 7.40
(t, J＝8.0 Hz, 1H), 7.33－7.30 (m, 2H), 4.58 (d, J＝5.6
Hz, 2H), 2.32 (s, 3H). HRMS (ES ＋ ) calcd for
C27H19N5O2F8I [M＋H]＋: 724.0456, found 724.0461.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-
4-yl)methyl)phthalamide 4I-I White powder, yield
30%; m.p. 179 － 182 ℃ ; 1H NMR (400 MHz,
DMSO-d6) δ: 9.96 (s, 1H), 9.04 (t, J＝5.6 Hz, 1H), 8.38
(s, 1H), 8.05 (d, J＝8.0 Hz, 1H), 7.75 (d, J＝7.6 Hz,
1H), 7.63－7.58 (m, 2H), 7.53－7.49 (m, 2H), 7.33－
7.26 (m, 3H), 7.12 (t, J＝7.6 Hz, 1H), 4.56 (d, J＝5.6
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(p-tolyl)-1H-1,2,3-triazol-4-yl)meth-
yl)phthalamide 4I-b White powder, yield 40%; m.p.
152－154 ℃; 1H NMR (400 MHz, DMSO-d6) δ: 10.02
(s, 1H), 9.06 (t, J＝5.6 Hz, 1H), 8.58 (s, 1H), 8.06 (d,
J＝8.0 Hz, 1H), 7.77 (d, J＝8.0 Hz, 1H), 7.64－7.61 (m,
3H), 7.51 (s, 1H), 7.34－7.30 (m, 4H), 4.54 (d, J＝5.6
Hz, 2H), 2.36 (s, 3H), 2.33 (s, 3H). HRMS (ES＋) calcd
for C28H21N5O2F7INa [M ＋ Na] ＋ : 742.0526, found
742.0529.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-
yl)methyl)phthalamide 4I-c White powder, yield
60%; m.p. 156 － 159 ℃ ; 1H NMR (400 MHz,
DMSO-d6) δ: 10.02 (s, 1H), 9.09 (t, J＝5.6 Hz, 1H),
8.64 (s, 1H), 8.06 (d, J＝8.0 Hz, 1H),7.79－7.76 (m,
3H), 7.62－7.56 (m, 3H), 7.50 (s, 1H), 7.34－7.30 (m,
2H), 4.54 (d, J＝5.6 Hz, 2H), 2.32 (s, 3H). HRMS
(ES ＋ ) calcd for C27H19N5O2F735ClI [M ＋ H] ＋
:
740.0160, found 740.0168; calcd for C27H19N5O2F737ClI
[M＋H]＋: 742.0131, found 742.0137.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)-
methyl)phthalamide 4I-d White powder, yield 80%;
Hz, 2H), 3.76 (s, 3H), 2.32 (s, 3H). HRMS (ES＋) calcd
＋
for C28H22N5O3F7I [M ＋ H] : 736.0656, found
1
m.p. 217－220 ℃; H NMR (400 MHz, DMSO-d6) δ:
736.0657.
10.02 (s, 1H), 9.14 (t, J＝5.6 Hz, 1H), 8.82 (s, 1H), 8.38
(d, J＝9.2 Hz, 2H), 8.08－8.05 (m, 3H), 7.77 (d, J＝8.0
Hz, 1H), 7.61 (d, J＝8.0 Hz, 1H), 7.46 (s, 1H), 7.35－
7.28 (m, 2H), 4.57 (d, J＝5.6 Hz, 2H), 2.31 (s, 3H).
HRMS (ES＋) calcd for C27H18N6O4F7INa [M＋Na]＋:
773.0220, found 773.0217.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(3-bromo-2-fluorophenyl)-1H-1,2,3-
triazol-4-yl)methyl)phthalamide 4I-j White powder,
1
yield 65%; m.p. 158－160 ℃; H NMR (400 MHz,
DMSO-d6) δ: 9.96 (s, 1H), 9.09 (t, J＝5.6 Hz, 1H), 8.51
(d, J＝2.0 Hz, 1H), 8.05 (d, J＝8.0 Hz, 1H), 7.92－7.88
(m, 1H), 7.83－7.76 (m, 2H), 7.63 (d, J＝8.4 Hz, 1H),
7.49 (s, 1H), 7.39－7.30 (m, 3H), 4.58 (d, J＝5.6 Hz,
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(3-fluorophenyl)-1H-1,2,3-triazol-4-
yl)methyl)phthalamide 4I-e White powder, yield
68%; m.p. 143 － 146 ℃ ; 1H NMR (400 MHz,
DMSO-d6) δ: 10.02 (s, 1H), 9.11 (t, J＝5.6 Hz, 1H),
8.69 (s, 1H), 8.06 (d, J＝8.0 Hz, 1H), 7.76 (d, J＝7.6
Hz, 1H), 7.66－7.54 (m, 4H), 7.47 (s, 1H), 7.34－7.30
(m, 3H), 4.55 (d, J＝5.6 Hz, 2H), 2.32 (s, 3H). HRMS
(ES＋) calcd for C27H19N5O2F8I [M＋H]＋: 724.0456,
found 724.0451.
2H), 2.33 (s, 3H). HRMS (ES ＋ ) calcd for
＋
C27H18N5O2F879BrI [M ＋ H]
: 801.9561, found
801.9562; calcd for C27H18N5O2F881BrI [M ＋ H] ＋ :
803.9540, found 803.9545.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(2-bromo-4-(trifluoromethyl)phenyl)-
1H-1,2,3-triazol-4-yl)methyl)phthalamide 4I-k
White powder, yield 78%; m.p. 190－193 ℃; 1H NMR
(400 MHz, DMSO-d6) δ: 9.98 (s, 1H), 9.10 (t, J＝5.6
Hz, 1H), 8.45 (s, 1H), 8.14 (d, J＝8.4 Hz, 1H), 8.05 (d,
J＝8.0 Hz, 1H), 7.99 (s, 1H), 7.92 (d, J＝8.0 Hz, 1H),
7.76 (d, J＝7.6 Hz, 1H), 7.58 (d, J＝8.4 Hz, 1H), 7.47
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(3-(trifluoromethyl)phenyl)-1H-1,2,3-
triazol-4-yl)methyl)phthalamide 4I-f White powder,
1
yield 76%; m.p. 192－195 ℃; H NMR (400 MHz,
596
www.cjc.wiley-vch.de
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 592—598

Synthesis and Insecticidal Evaluation of Novel Phthalic Diamides Containing 1,2,3-Triazoles
(s, 1H), 7.33－7.28 (m, 2H), 4.60 (d, J＝5.6 Hz, 2H),
2.33 (s, 3H). HRMS (ES＋) calcd for C28H18N5O2-
pound 3II (215 mg, 0.35 mmol), CuI (27 mg, 0.14
mmol), Et3N (8 mg, 0.07 mmol) and 10 mL ethyl ace-
tate were then added and the reaction was stirred at
room temperature. The progress of the reaction was
monitored by TLC. After the completion of reaction, the
solvent was removed under reduced pressure, and the
residue was purified by silica gel column chromatogra-
phy using petroleum ether/ethyl acetate as the eluting
solution to afford the target compounds 4II.
F1079BrI [M＋H]＋: 851.9529, found 851.9539; calcd for
＋
C28H18N5O2F1081BrI [M ＋ H] : 853.9508, found
853.9521.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(3-fluoro-4-methoxyphenyl)-1H-1,2,3-
triazol-4-yl)methyl)phthalamide 4I-l White powder,
1
yield 70%; m.p. 196－198 ℃; H NMR (400 MHz,
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(2-(1-phenyl-1H-1,2,3-triazol-4-yl)pro-
pan-2-yl)phthalamide 4II-a White powder, yield
50%; m.p. 190－192 ℃; 1H NMR (400 MHz,
DMSO-d6) δ: 10.02 (s, 1H), 8.78 (s, 1H), 8.76 (s, 1H),
8.07 (d, J＝8.0 Hz, 1H), 7.77－7.72 (m, 3H), 7.68 (d,
J＝8.0 Hz, 1H), 7.50 (s, 1H), 7.44－7.38 (m, 3H), 7.33
－7.27 (m, 2H), 2.31 (s, 3H), 1.77 (s, 6H); HRMS (ES
＋) calcd for C29H24N5O2F7I [M＋H]＋: 734.0863, found
734.0865.
DMSO-d6) δ: 10.00 (s, 1H), 9.08 (t, J＝5.6 Hz, 1H),
8.56 (s, 1H), 8.06 (d, J＝7.6 Hz, 1H), 7.76 (d, J＝7.6
Hz, 1H), 7.67 (dd, J＝12.0, 2.4 Hz, 1H), 7.61－7.55 (m,
2H), 7.48 (s, 1H), 7.34－7.29 (m, 3H), 4.54 (d, J＝5.6
Hz, 2H), 3.91 (s, 3H), 2.32 (s, 3H). HRMS (ES＋) calcd
＋
for C28H21N5O3F8I [M ＋ H] : 754.0561, found
754.0567.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(2-bromo-6-fluorophenyl)-1H-1,2,3-
triazol-4-yl)methyl)phthalamide 4I-m White pow-
der, yield 63%; m.p. 135－138 ℃; 1H NMR (400 MHz,
DMSO-d6) δ: 10.02 (s, 1H), 9.12 (t, J＝5.6 Hz, 1H),
8.37 (s, 1H), 8.05 (d, J＝7.6 Hz, 1H), 7.78－7.74 (m,
2H), 7.67－7.55 (m, 3H), 7.51 (s, 1H), 7.38 (d, J＝8.4
Hz, 1H), 7.31 (t, J＝8.0 Hz, 1H), 4.60 (d, J＝5.6 Hz,
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(2-(1-(3-(trifluoromethyl)phenyl)-1H-1,2,
3-triazol-4-yl)propan-2-yl)phthalamide 4II-b White
1
powder, yield 86%; m.p. 198－201 ℃; H NMR (400
MHz, DMSO-d6) δ: 9.90 (s, 1H), 8.87 (s, 1H), 8.81 (s,
1H), 8.16 (s, 1H), 8.06 (d, J＝8.0 Hz, 2H), 7.79 (d, J＝
7.6 Hz, 1H), 7.75－7.68 (m, 2H), 7.63 (d, J＝8.0 Hz,
1H), 7.41 (s, 1H), 7.30 (t, J＝8.0 Hz, 1H), 7.13 (d, J＝
8.8 Hz, 1H), 2.28 (s, 3H), 1.78 (s, 6H). HRMS (ES＋)
calcd for C30H23N5O2F10I [M＋H]＋: 802.0737, found
802.0740.
2H), 2.34 (s, 3H). HRMS (ES ＋ ) calcd for
＋
C27H18N5O2F879BrI [M ＋ H]
: 801.9561, found
801.9560; calcd for C27H18N5O2F881BrI [M ＋ H] ＋ :
803.9540, found 803.9545.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(4-bromo-2,5-difluorophenyl)-1H-1,2,
3-triazol-4-yl)methyl)phthalamide 4I-n White pow-
der, yield 68%; m.p. 238－240 ℃; 1H NMR (400 MHz,
DMSO-d6) δ: 9.96 (s, 1H), 9.10 (t, J＝5.6 Hz, 1H), 8.50
(d, J＝1.2 Hz, 1H), 8.12－8.05 (m, 2H), 7.95 (dd, J＝
8.4, 6.8 Hz, 1H), 7.76 (d, J＝7.6 Hz, 1H), 7.60 (d, J＝
8.0 Hz, 1H), 7.48 (s, 1H), 7.34－7.30 (m, 2H), 4.57 (d,
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(2-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,
3-triazol-4-yl)propan-2-yl)phthalamide 4II-c White
1
powder, yield 90%, m.p. 202－204 ℃; H NMR (400
MHz, DMSO-d6) δ: 10.06 (s, 1H), 8.88 (s, 1H), 8.83 (s,
1H), 8.08 (d, J＝7.6 Hz, 1H), 7.97 (d, J＝8.4 Hz, 2H),
7.82 (d, J＝8.4 Hz, 2H), 7.78 (d, J＝7.6 Hz, 1H), 7.69
(d, J＝8.8 Hz, 1H), 7.48 (s, 1H), 7.34－7.29 (m, 2H),
2.32 (s, 3H), 1.79 (s, 6H). HRMS (ES＋) calcd for
C30H23N5O2F10I [M＋H]＋: 802.0737, found 802.0741.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(2-(1-(3-bromo-2-fluorophenyl)-1H-1,2,3-
triazol-4-yl)propan-2-yl)phthalamide 4II-d White
J＝5.6 Hz, 2H), 2.31 (s, 3H). HRMS (ES＋) calcd for
＋
C27H17N5O2F979BrI [M ＋ H]
: 819.9467, found
819.9472; calcd for C27H17N5O2F981BrI [M ＋ H] ＋ :
821.9446, found 821.9453.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-((1-(2,6-difluoro-4-iodophenyl)-1H-1,2,3-
triazol-4-yl)methyl)phthalamide 4I-o White powder,
1
1
powder, yield 78%; m.p. 125－128 ℃; H NMR (400
yield 65%; m.p. 185－187 ℃; H NMR (400 MHz,
MHz, DMSO-d6) δ: 9.91 (s, 1H), 8.79 (s, 1H), 8.65 (d,
J＝2.4 Hz, 1H), 8.05 (d, J＝7.6 Hz, 1H), 7.88 (t, J＝8.0
Hz, 1H), 7.81 (t, J＝8.0 Hz, 1H), 7.73 (d, J＝7.6 Hz,
1H), 7.66 (d, J＝8.4 Hz, 1H), 7.45 (s, 1H), 7.35 (t, J＝
8.0 Hz, 1H), 7.29 (t, J＝7.6 Hz, 1H), 7.11 (d, J＝8.8 Hz,
DMSO-d6) δ: 9.96 (s, 1H), 9.07 (t, J＝5.6 Hz, 1H), 8.40
(s, 1H), 8.05 (d, J＝8.0 Hz, 1H), 7.92 (d, J＝7.6 Hz,
2H), 7.77 (d, J＝7.6 Hz, 1H), 7.66 (d, J＝8.4 Hz, 1H),
7.51 (s, 1H), 7.39 (d, J＝8.4 Hz, 1H), 7.31 (t, J＝8.0 Hz,
1H), 4.57 (d, J＝5.6 Hz, 2H), 2.33 (s, 3H). HRMS
(ES＋) calcd for C27H17N5O2F9I2 [M＋H]＋: 867.9328,
found 867.9333.
1H), 2.31 (s, 3H), 1.78 (s, 6H). HRMS (ES＋) calcd for
＋
C29H22N5O2F879BrI [M ＋ H]
: 829.9874, found
829.9878; calcd for C29H22N5O2F881BrI [M ＋ H] ＋ :
831.9853, found 831.9863.
General procedure for the synthesis of 4II
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(2-(1-(2-bromo-4-(trifluoromethyl)phe-
nyl)-1H-1,2,3-triazol-4-yl)propan-2-yl)phthalamide
4II-e White powder, yield 81%; m.p. 232－235 ℃;
1H NMR (400 MHz, DMSO-d6) δ: 9.94 (s, 1H), 8.75 (s,
1H), 8.60 (s, 1H), 8.13 (d, J＝8.4 Hz, 1H), 8.07－8.04
Different aniline (0.5 mmol) was dissolved in
CH3CN (5 mL) in a 25 mL round-bottomed flask and
cooled to 0 ℃ in an ice bath. To this stirred mixture
was added t-BuONO (78 mg, 0.75 mmol) followed by
TMSN3 (69 mg, 0.6 mmol) dropwise. The resulting so-
lution was stirred at room temperature for 1－2 h. Com-
Chin. J. Chem. 2014, 32, 592—598
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
597

Chen et al.
FULL PAPER
(m, 2H), 7.90 (dd, J＝8.4, 1.6 Hz, 1H), 7.74 (d, J＝7.6
Hz, 1H), 7.60 (d, J＝8.4 Hz, 1H), 7.42 (s, 1H), 7.29 (t,
J＝8.0 Hz, 1H), 7.08 (d, J＝8.4 Hz, 1H), 2.31 (s, 3H),
1.80 (s, 6H). HRMS (ES＋) calcd for C30H22N5O2F10-
gram, No. 2011AA10A207), and the National Natural
Science Foundation of China (Nos. 21372079;
21272071). This work was also partly supported by the
National Key Technology R&D Program of China (No.
2011BAE06B01) and the Fundamental Research Funds
for the Central Universities.
79BrI [M＋H]＋: 879.9842, found 879.9843; calcd for
＋
C30H22N5O2F1081BrI [M ＋ H] : 881.9821, found
881.9825.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(2-(1-(3-fluoro-4-methoxyphenyl)-1H-1,2,
3-triazol-4-yl)propan-2-yl)phthalamide 4II-f White
References
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1H), 8.06 (d, J＝7.6 Hz, 1H), 7.73 (d, J＝7.6 Hz, 1H),
7.68－7.62 (m, 2H), 7.55 (d, J＝8.8 Hz, 1H), 7.46 (s,
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(s, 3H), 2.31 (s, 3H), 1.76 (s, 6H). HRMS (ES＋) calcd
for C30H25N5O3F8I [M ＋ H] : 782.0874, found
＋
782.0874.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(2-(1-(4-bromo-2,5-difluorophenyl)-1H-
1,2,3-triazol-4-yl)propan-2-yl)phthalamide
4II-g
White powder, yield 86%; m.p. 221－223 ℃; 1H NMR
(400 MHz, DMSO-d6) δ: 9.94 (s, 1H), 8.82 (s, 1H), 8.65
(d, J＝2.0 Hz, 1H), 8.08－8.04 (m, 2H), 7.99 (dd, J＝
8.0, 6.8 Hz, 1H), 7.74 (d, J＝7.6 Hz, 1H), 7.64 (d, J＝
8.8 Hz, 1H), 7.44 (s, 1H), 7.30 (t, J＝8.0 Hz, 1H), 7.17
(d, J＝8.4 Hz, 1H), 2.29 (s, 3H), 1.77 (s, 6H). HRMS
(ES ＋ ) calcd for C29H21N5O2F979BrI [M ＋ H] ＋
:
847.9780, found 847.9778; calcd for C29H21N5O2F981BrI
[M＋H]＋: 849.9759, found 847.9762.
3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(2-(1-(2,6-difluoro-4-iodophenyl)-1H-1,2,
3-triazol-4-yl)propan-2-yl)phthalamide 4II-h White
1
powder, yield 79%; m.p. 219－221 ℃; H NMR (400
MHz, DMSO-d6) δ: 9.92 (s, 1H), 8.76 (s, 1H), 8.49 (s,
1H), 8.05 (d, J＝8.0 Hz, 1H), 7.91 (d, J＝7.6 Hz, 2H),
7.74 (d, J＝7.6 Hz, 1H), 7.68 (d, J＝8.8 Hz, 1H), 7.47
(s, 1H), 7.31－7.25 (m, 2H), 2.30 (s, 3H), 1.76 (s, 6H).
HRMS (ES＋) calcd for C29H21N5O2F9I2 [M＋H]＋:
895.9641, found 895.9648.
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3-Iodo-N1-(2-methyl-4-(perfluoropropan-2-yl)-
phenyl)-N2-(2-(1-(2-bromo-6-fluorophenyl)-1H-1,2,3-
triazol-4-yl)propan-2-yl)phthalamide 4II-i
White
1
powder, yield 71%; m.p. 162－164 ℃; H NMR (400
MHz, DMSO-d6) δ: 9.98 (s, 1H), 8.74 (s, 1H), 8.45 (s,
1H), 8.05 (d, J＝8.0 Hz, 1H), 7.74－7.72 (m, 2H), 7.65
－7.55 (m, 3H), 7.47 (s, 1H), 7.29 (t, J＝8.0 Hz, 1H),
7.21 (d, J＝8.8 Hz, 1H), 2.32 (s, 3H), 1.78 (s, 6H).
HRMS (ES＋) calcd for C29H22N5O2F879BrI [M＋H]＋:
829.9874, found 829.9879; calcd for C29H22N5O2F881BrI
[M＋H]＋: 831.9853, found 831.9862.
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Acknowledgement
This work was financially supported by the National
Basic Research Program of China (973 Program, No.
2010CB126100), the National High Technology Re-
search and Development Program of China (863 Pro-
(Lu, Y.)
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