Design, synthesis, structure-activity relationship and insecticidal activities of trifluoromethyl-containing sulfiliminyl and sulfoximinyl phthalic acid diamide structure

Article abstract of DOI:10.1002/cjoc.201400223

Due to a novel mode action, low toxicity to mammals and low residue characteristics, phthalic acid diamides have aroused considerable interests in agricultural chemistry. With introduction of N-cyano, N-trifluoroacetyl, N-carbamoylsulfiliminyl and sulfoximinyl substituents into phthalamides, 12 novel derivatives containing trifluoromethyl moiety were designed and synthesized. All title compounds were characterized by ¹H NMR and high-resolution mass spectrometry. The preliminary results of biological activity assessment indicated that some title compounds exhibited moderate to good insecticidal activities against oriental armyworm (Pseudaletia separata Walker). In particular, Va gave higher activity against oriental armyworm and diamondback moth. The present work reported that the new trifluoromethylated diamides incorporating N-trifluoroacetylsulfoximinyl moieties are potential lead compounds for further structure optimization, providing some insight into the relating structure-activity relationship. Copyright

Full text of DOI:10.1002/cjoc.201400223

FULL PAPER
DOI: 10.1002/cjoc.201400223
Design, Synthesis, Structure-Activity Relationship and Insecti-
cidal Activities of Trifluoromethyl-Containing Sulfiliminyl
and Sulfoximinyl Phthalic Acid Diamide Structure
Sha Zhou,a,† Tao Yan,b,† Sha Zhou,a Xuewen Hua,a Baolei Wang,a Yucheng Gu,c Lixia Xiong,a
Yongqiang Li,a and Zhengming Li*,a
a State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and
Engineering (Tianjin), Nankai University, Tianjin 300071, China
b School of Mechanical Engineering, Tianjin Polytechnic University, Tianjin 300071, China
c Syngenta Jealott’s Hill International Research Centre, Bracknell, Berkshire, RG426EY, UK
Due to a novel mode action, low toxicity to mammals and low residue characteristics, phthalic acid diamides
have aroused considerable interests in agricultural chemistry. With introduction of N-cyano, N-trifluoroacetyl,
N-carbamoylsulfiliminyl and sulfoximinyl substituents into phthalamides, 12 novel derivatives containing trifluoro-
1
methyl moiety were designed and synthesized. All title compounds were characterized by H NMR and high-reso-
lution mass spectrometry. The preliminary results of biological activity assessment indicated that some title com-
pounds exhibited moderate to good insecticidal activities against oriental armyworm (Pseudaletia separata Walker).
In particular, Va gave higher activity against oriental armyworm and diamondback moth. The present work reported
that the new trifluoromethylated diamides incorporating N-trifluoroacetylsulfoximinyl moieties are potential lead
compounds for further structure optimization, providing some insight into the relating structure-activity relation-
ship.
Keywords insecticidal activity, ryanodine receptor, sulfilimines, sulfoximines, trifluoromethylated
O
Introduction
O
S
R1
N
I
HN
O
(c)
In order to overcome resistance and eco-biological
problems associated with conventional insecticides,
there is an urgent need to discover novel potent insecti-
cides with a new mode of action.[1] The ryanodine re-
ceptor (RyR) represents a new target to study in an in-
tegrated strategies for pest management.[2-4] There are
commercial products namely: flubendiamide (Figure 1,
A),[5] chlorantraniliprole (B) and cyantraniliprole (C).[6-8]
They evoke massive calcium release and disrupt cal-
cium homeostasis in RyR channels resulting in distinct
pharmacological characteristics.[9,10]
O
R2
O
N
H
Xn
N
R3
Ar Ym
(b)
CF3
F
O
CF3
Flubendiamide
(a)
phthalic acid diamides
A
D
Br
Br
H
H
N
O
N
O
H3C
H3C
Cl
H
N
H
N
N
N
N
N
Cl
Cl
The chemical structures of reported potent phthala-
mides could be divided into three moieties (Figure 1, D):
(a) phthalic acid, (b) aromatic amine, (c) aliphatic
amine.[11] Most of the previous modifications are related
to parts a and b.[12-16] As fluorine usually plays an active
role in pharmaceutical and crop protection agents,[17,18]
the introduction of a trifluoromethyl group could bring
changes in the physical, chemical and biological proper-
ties.[19-21]
O
O
NC
CH3
N
CH3
N
Cyazypyr
Rynaxypyr
B
anthranilic diamides
C
Figure 1 Chemical structures of diamides and general structure
of flubendiamide.
In our previous work,[22] the novel phthalamides
containing sulfiliminyl and sulfoximinyl moieties as
*
E-mail: nkzml@vip.163.com; Tel.: 0086-022-23503732; Fax: 0086-022-23503732
Received April 16, 2014; accepted May 20, 2014; published online June 13, 2014.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201400223 or from the author.
† Co-first authors Zhou Sha and Yan Tao contributed equally to this work.
Chin. J. Chem. 2014, 32, 567—572
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567

Zhou et al.
FULL PAPER
potential ryanodine receptor modulators were reported.
Some sulfiliminyl and sulfoximinyl derivatives con-
taining iodine and nitro group in part a showed excellent
activities against oriental armyworm (Pseudaletia
separata Walker) and diamondback moths (Plutella
xylostella (L.)). What’s more, two other compounds
exhibited outstanding activity against diamondback
moths, which were better than flubendiamide.
Beijing, China) and were uncorrected. Yields were not
optimized. Reagents were all analytically or chemically
pure. All solvents and liquid reagents were dried by
standard methods in advance and distilled before use.
Flubendiamide was used as the control and synthesized
according to the literature.[23] Compounds 1a－1b,[24-26]
and 2-methyl-1-(methylthio) propan-2-amine[27] were
synthesized referring to the methods reported in the lit-
erature.
Encouraged by the above experimental results, a se-
ries of novel trifluoromethyl-containing sulfiliminyl and
sulfoximinyl phthalic acid diamide structures were syn-
General synthetic procedure for compounds 3a－3b
1
thesized and characterized by H NMR, HRMS (ele-
N-(2-Methyl-1-(methylthio)propan-2-yl)-N'-(substi-
tuted phenyl) phthalamide derivatives 3a－3b were
synthesized in moderate yields by the method reported
in the literature.[28] The melting point and 1H NMR data
were consistent with the literature.
mental analysis) and bioassay. The synthetic procedure
was outlined in Scheme 1. Their bioactivities against
oriental armyworm and diamondback moth were tested
accordingly.
General synthetic procedure for compounds Ia－Ib
Experimental
A mixture of 1.0 mmol of 3a－3d and 0.046 g (1.1
mmol) of cyanamide in 20 mL of acetonitrile was
cooled below 0 ℃. To this solution was added 0.322 g
(1 mmol) of iodobenzenediacetate all at once. The reac-
tion mixture was allowed to stir below 0 ℃ for 10 min
and slowly warmed to room temperature over 1.5 h, the
progress of the reaction was followed by TLC. Excess
oxidant was destroyed by adding 5 mL of 2.5% aq. so-
dium metabisulfite. The solution was washed with dilute
hydrochloric acid, water, an aqueous sodium carbonate
solution and water respectively and dried over anhy-
Instruments
1H NMR spectra were recorded at 400 MHz using a
Bruker AV 400 spectrometer (Bruker Co., Switzerland)
in CDCl3 or DMSO-d6 solution with tetramethylsilane
as the internal standard. High-resolution mass spec-
trometry (HRMS) data were obtained on a Varian
QFT-ESI instrument. Flash chromatography was per-
formed with silica gel (200－300 mesh). The melting
points were determined on an X-4 binocular microscope
melting point apparatus (Beijing Tech Instruments Co.,
Scheme 1
CF3
S
S
S
X
(1) N(Et)3, CH2Cl2,
(2) HCl
X
X
HN
O
H2N
N
H2N
(a)
O
N
H
O
O
O
S
CF3
(3) N(Et)3, CH2Cl2,
O
O
Cl
O
O
1a - 1b
2a - 2b
3a - 3b
O
O
N
S
O
CF3
CF3
N
S
CF3
X
HN
X
HN
O
(c)
O
O
(d)
N
H
N
H
CF3
CN
N
CN
N
S
(d)
O
S
X
HN
O
X
HN
IVa - IVb
Va - Vb
O
O
O
O
O
N
H
CF3
N
H
CF3
N
S
NH2
CF3
N
NH2
CF3
S
O
(b)
X
HN
O
X
HN
O
Ia - Ib
O
O
VIa - VIb
(c)
O
N
H
N
H
(c)
1a - 1b
IIa - IIb
IIIa - IIIb
a: X = I; b: X = NO2
Reagent and conditions: (a) PhI(OAc)2, NH2CN, CH3CN, 0 ℃ to r.t., (b) CF3COOH, CH2Cl2, ice bath, (c) mCPBA, K2CO3, EtOH, 0 ℃ to r.t., (d)
(CF3CO)2O, CH2Cl2, r.t.
568
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 567—572

Insecticidal Activities of Sulfiliminyl and Sulfoximinyl Phthalic Acid Diamide Structure
drous sodium sulfate. The solvent was removed under
reduced pressure, and the residue was purified by silica
gel column chromagraphy.[29-32]
8.10 Hz, 1H, Ar-H), 8.21 (s, 1H, Ar-H), 8.01 (d, J＝
7.60 Hz, 1H, Ar-H), 7.87 (d, J＝8.00 Hz, 1H, Ar-H),
7.78 (t, J＝8.00 Hz, 1H, Ar-H), 7.62 (t, J＝8.00 Hz, 1H,
Ar-H), 7.49 (d, J＝7.60 Hz, 1H, Ar-H), 5.40 (s, 2H,
CONH2), 3.40 (d, J＝13.50 Hz, 1H, SCH2), 2.76 (d, J＝
13.40 Hz, 1H, SCH2), 2.44 (s, 3H, SCH3), 1.40 [s, 3H,
SCH2C(CH3)2], 1.37 [s, 3H, SCH2C(CH3)2]. HRMS
calcd for C21H22F3N5O5SNa ([M＋Na]＋ ) 536.1186,
found 536.1182.
N2-(1-(N-Cyano-S-methylsulfinimidoyl)-2-methyl-
propan-2-yl)-3-iodo-N1-(3-(trifluoromethyl)phenyl)-
phthalamide (Ia) White solid, yield 95.1%, m.p. 90
－91 ℃. 1H NMR (400 MHz, CDCl3-d6) δ: 9.59 (s, 1H,
Ar-NH), 7.82 (s, 1H, Ar-H), 7.79 (d, J＝8.0 Hz, 1H,
Ar-H), 7.59 (s, 1H, Ar-H), 7.51 (d, J＝7.7 Hz, 1H,
Ar-H), 7.29 (d, J＝5.0 Hz, 2H, Ar-H), 7.18 (t, J＝7.8
Hz, 1H, Ar-H), 6.60 (s, 1H, CNH), 3.92 (d, J＝13.6 Hz,
1H, SCH2), 3.26 (d, J＝13.7 Hz, 1H, SCH2), 2.69 (s, 3H,
Ar-CH3), 1.60 [s, 3H, SCH2(CH3)2], 1.57 [s, 3H,
SCH2(CH3)2]. HRMS calcd for C21H20F3IN4O2SNa
([M＋Na]＋) 599.0196, found 599.0194.
General synthetic procedure for compounds IIIa－
IIIb
3-Chloroperoxybenzoic acid (mCPBA) and potas-
sium carbonate were mixed in ethanol at 0 ℃ for 20
min, a solution of IIa－IIb in ethanol was added drop-
wise over 45 min. The reaction mixture was then stirred
for 30 min and poured into water. The produced pre-
cipitate was filtered and washed with dilute hydrochlo-
ric acid, water, an aqueous sodium carbonate solution
and water successively or was further purified by silica
gel column chromagraphy to give compounds IIIa－
IIIb.[31,33]
N2-(1-(N-Cyano-S-methylsulfinimidoyl)-2-methyl-
propan-2-yl)-3-nitro-N1-(3-(trifluoromethyl)phenyl)-
phthalamide (Ib) White solid, yield 92.7%, m.p. 135
－136 ℃. 1H NMR (400 MHz, DMSO-d6) δ: 10.87 (s,
1H, Ar-NH), 8.84 (s, 1H, CNH), 8.25 (d, J＝7.4 Hz, 1H,
Ar-H), 8.15 (s, 1H, Ar-H), 8.07 (d, J＝7.5 Hz, 1H,
Ar-H), 7.91 (d, J＝8.4 Hz, 1H, Ar-H), 7.81 (t, J＝8.0
Hz, 1H, Ar-H), 7.63 (t, J＝8.2 Hz, 1H, Ar-H), 7.50 (d,
J＝8.0 Hz, 1H, Ar-H), 3.83 (d, J＝13.8 Hz, 1H, SCH2),
3.23 (d, J＝13.7 Hz, 1H, SCH2), 2.78 (s, 3H, SCH3),
1.44 [s, 3H, SCH2(CH3)2], 1.37 [s, 3H, SCH2(CH3)2].
N2-(1-(N-Carbamoyl-S-methylsulfonimidoyl)-2-
methylpropan-2-yl)-3-iodo-N1-(3-(trifluoromethyl)-
phenyl)phthalamide (IIIa) White solid, yield 86.8%,
1
m.p. 185－186 ℃. HNMR (400 MHz, DMSO-d6) δ:
HRMS calcd for C21H20F3N5O4SNa ([M ＋ Na] ＋
)
10.56 (s, 1H, Ar-NH), 8.43 (s, 1H, CNH), 8.15 (s, 1H,
Ar-H), 8.03 (d, J＝7.82 Hz, 1H, Ar-H), 7.92 (d, J＝7.90
Hz, 1H, Ar-H), 7.69 (d, J＝7.60 Hz, 1H, Ar-H), 7.61 (t,
J＝8.00 Hz, 1H, Ar-H), 7.46 (d, J＝7.72 Hz, 1H, Ar-H),
7.28 (t, J＝7.70 Hz, 1H, Ar-H), 6.23 (s, 1H, CONH2),
5.96 (s, 1H, CONH2), 3.99 (d, J＝14.40 Hz, 1H, SCH2),
3.86 (d, J＝14.40 Hz, 1H, SCH2), 3.25 (s, 3H, SCH3),
1.54 [s, 6H, SCH2(CH3)2]. HRMS calcd for C21H22F3I-
N4O4SNa ([M＋Na]＋) 633.0251, found 633.0250.
518.1080, found 518.1089.
General synthetic procedure for compounds IIa－
IIb
To a solution of Ia－Ib (1 mmol) in dichloro-
methane, trifluoroacetic acid (0.342 g, 3 mmol) was
added dropwise over 15 min at 0 ℃. The reaction mix-
ture was stirred at 0 ℃ for 0.5 h (monitored by TLC).
The resulting mixture was washed with dilute hydro-
chloric acid, water, an aqueous sodium carbonate solu-
tion and water successively. The organic layer was dried
(MgSO4) and concentrated in vacuo to furnish com-
pounds IIa－IIb.[33]
N2-(1-(N-Carbamoyl-S-methylsulfonimidoyl)-2-
methylpropan-2-yl)-3-nitro-N1-(3-(trifluoromethyl)-
phenyl)phthalamide (IIIb) White solid, yield 93.0%,
1
m.p. 151－153 ℃. H NMR (400 MHz, DMSO-d6) δ:
10.81 (s, 1H, Ar-NH), 8.66 (s, 1H, CNH), 8.23 (d, J＝
8.00 Hz, 1H, Ar-H), 8.15 (s, 1H, Ar-H), 8.04 (d, J＝
7.40 Hz, 1H, Ar-H), 7.92 (d, J＝7.90 Hz, 1H, Ar-H),
7.80 (t, J＝7.70 Hz, 1H, Ar-H), 7.62 (t, J＝6.20 Hz, 1H,
Ar-H), 7.49 (d, J＝7.40 Hz, 1H, Ar-H), 6.23 (s, 1H,
CONH2), 5.96 (s, 1H, CONH2), 3.94 (d, J＝14.30 Hz,
1H, SCH2), 3.82 (d, J＝14.30 Hz, 1H, SCH2), 3.24 (s,
3H, SCH3), 1.48 [s, 6H, SCH2C(CH3)2]. HRMS calcd
for C21H22F3N5O6SNa ([M＋Na]＋ ) 552.1141, found
552.1136.
N2-[1-(N-Carbamoyl-S-methylsulfinimidoyl)-2-
methylpropan-2-yl]-3-iodo-N1-[3-(trifluoromethyl)-
phenyl]phthalamide (IIa) White solid, yield 70.3%,
1
m.p. 173－174 ℃. H NMR (400 MHz, CDCl3-d6) δ:
10.54 (s, 1H, Ar-NH), 8.52 (s, 1H, CNH), 8.18 (s, 1H,
Ar-H), 8.02 (d, J＝7.90 Hz, 1H, Ar-H), 7.90 (d, J＝8.20
Hz, 1H, Ar-H), 7.68 (d, J＝7.60 Hz, 1H, Ar-H), 7.61 (t,
J＝8.00 Hz, 1H, Ar-H), 7.46 (d, J＝7.72 Hz, 1H, Ar-H),
7.27 (t, J＝7.70 Hz, 1H, Ar-H), 5.29 (s, 2H, CONH2),
3.56 (d, J＝13.50 Hz, 1H, SCH2), 3.22 (d, J＝13.50 Hz,
1H, SCH2), 2.54 (s, 3H, SCH3), 1.40 [d, J＝21.30 Hz,
6H, SCH2C(CH3)2]. HRMS calcd for C21H22F3IN4O3S-
Na ([M＋Na]＋) 617.0302, found 617.0299.
General synthetic procedure for compounds IVa－
IVb
To a solution of Ia－Ib (1 mmol) in dichlorometh-
ane, trifluoroacetic anhydride (0.630 g, 3 mmol) was
added dropwise over 15 min at room temperature. The
reaction mixture was stirred for 0.5 h (monitored by
TLC). The resulting mixture was washed with dilute
hydrochloric acid, water, an aqueous sodium carbonate
N2-[1-(N-Carbamoyl-S-methylsulfinimidoyl)-2-
methylpropan-2-yl]-3-nitro-N1-[3-(trifluoromethyl)-
phenyl]phthalamide (IIb) White solid, yield 66.5%,
1
m.p. 133－135 ℃. H NMR (400 MHz, DMSO-d6) δ:
10.78 (s, 1H, Ar-NH), 8.58 (s, 1H, CNH), 8.23 (d, J＝
Chin. J. Chem. 2014, 32, 567—572
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Zhou et al.
FULL PAPER
solution and water successively. The organic layer was
dried (MgSO4) and concentrated in vacuo to furnish
compounds IVa－IVb.[34]
Hz, 1H, Ar-H), 7.49 (d, J＝8.1 Hz, 1H, Ar-H), 4.20 (d,
J＝14.9 Hz, 1H, SCH2), 4.13 (d, J＝14.3 Hz, 1H,
SCH2), 3.65 (s, 3H, SCH3), 1.51 [s, 6H, SCH2C(CH3)2].
N2-{1-[S-Methyl-N-(2,2,2-trifluoroacetyl)sulfini-
midoyl]-2-methylpropan-2-yl}3-iodo-N1-[3-(trifluoro-
methyl)phenyl]phthalamide (IVa) White solid, yield
93.0%, m.p. 217 － 219 ℃ . 1H NMR (400 MHz,
DMSO-d6) δ: 10.63 (s, 1H, Ar-NH), 8.60 (s, 1H, CNH),
8.15 (s, 1H, Ar-H), 8.04 (d, J＝8.00 Hz, 1H, Ar-H),
7.93 (d, J＝8.20 Hz, 1H, Ar-H), 7.75 (d, J＝7.62 Hz,
1H, Ar-H), 7.61 (t, J＝8.10 Hz, 1H, Ar-H), 7.47 (d, J＝
7.80 Hz, 1H, Ar-H), 7.30 (t, J＝7.70 Hz, 1H, Ar-H),
3.98 (d, J＝13.60 Hz, 1H, SCH2), 3.38 (d, J＝13.60 Hz,
1H, SCH2), 2.82 (s, 3H, SCH3), 1.49 [s, 3H, SCH2C-
HRMS calcd for C22H20F6N4O6SNa ([M ＋ Na] ＋
)
605.0900, found 605.0892.
General synthetic procedure for compounds VIa－
VIb
The procedure was similar to those of the com-
pounds IIIa － IIIb. Using intermediates Ia － Ib,
3-chloroperoxybenzoic acid (mCPBA) and potassium
carbonate as materials, compounds VIa－Vib were ob-
tained.
N2-(1-(N-Cyano-S-methylsulfonimidoyl)-2-methyl-
propan-2-yl)-3-iodo-N1-(3-(trifluoromethyl)phenyl)-
phthalamide (VIa) White solid, yield 86.8%, m.p.
185－186 ℃. 1H NMR (400 MHz, DMSO-d6) δ: 10.64
(s, 1H, Ar-NH), 8.60 (s, 1H, CNH), 8.17 (s, 1H, Ar-H),
8.05 (d, J＝8.30 Hz, 1H, Ar-H), 7.93 (d, J＝8.30 Hz,
1H, Ar-H), 7.72 (d, J＝7.66 Hz, 1H, Ar-H), 7.61 (t, J＝
7.70 Hz, 1H, Ar-H), 7.49 (d, J＝7.66 Hz, 1H, Ar-H),
7.31 (s, 1H, Ar-H), 4.17 (d, J＝14.20 Hz, 1H, SCH2),
4.07 (d, J＝14.20 Hz, 1H, SCH2), 3.59 (s, 3H, SCH3),
1.56 [d, J＝5.30 Hz, 6H, SCH2C(CH3)2]. HRMS calcd
for C21H22F3IN4O4SNa ([M＋Na]＋) 633.0251, found
633.0250.
(CH3)2], 1.37 [s, 3H, SCH2C(CH3)2]. HRMS calcd for
＋
C22H20F6IN3O3SNa ([M ＋ Na] ) 670.0066, found
670.0065.
N2-{1-[S-Methyl-N-(2,2,2-trifluoroacetyl)sulfinimi-
doyl]-2-methylpropan-2-yl}-3-nitro-N1-[3-(trifluoro-
methyl)phenyl]phthalamide (IVb) White solid, yield
91.0%, m.p. 200 － 201 ℃ . 1H NMR (400 MHz,
DMSO-d6) δ: 10.89 (s, 1H, Ar-NH), 8.82 (s, 1H, CNH),
8.25 (d, J＝8.30 Hz, 1H, Ar-H), 8.16 (s, 1H, Ar-H),
8.09 (d, J＝7.60 Hz, 1H, Ar-H), 7.91 (d, J＝8.20 Hz,
1H, Ar-H), 7.82 (t, J＝8.00 Hz, 1H, Ar-H), 7.63 (t, J＝
7.60 Hz, 1H, Ar-H), 7.50 (d, J＝8.40 Hz, 1H, Ar-H), 3.94
(d, J＝13.60 Hz, 1H, SCH2), 3.39 (d, J＝13.60 Hz, 1H,
SCH2), 2.81 (s, 3H, SCH3), 1.43 [s, 3H, SCH2C(CH3)2],
1.29 [s, 3H, SCH2C(CH3)2]. HRMS calcd for C22H20F6-
N4O5SNa ([M＋Na]＋) 589.0951, found 589.0954.
N2-[1-(N-Cyano-S-methylsulfonimidoyl)-2-methyl-
propan-2-yl]-3-nitro-N1-[3-(trifluoromethyl)phenyl]-
phthalamide (VIb) White solid, yield 93.0%, m.p.
1
151－153 ℃. HNMR (400 MHz, DMSO-d6) δ: 10.87
(s, 1H, Ar-NH), 8.82 (s, 1H, CNH), 8.25 (d, J＝8.20 Hz,
1H, Ar-H), 8.17 (s, 1H, Ar-H), 8.07 (d, J＝7.60 Hz, 1H,
Ar-H), 7.93 (d, J＝8.10 Hz, 1H, Ar-H), 7.82 (t, J＝8.00
Hz, 1H, Ar-H), 7.63 (t, J＝8.00 Hz, 1H, Ar-H), 7.50 (d,
J＝7.80 Hz, 1H, Ar-H), 4.16 (d, J＝14.70 Hz, 1H,
SCH2), 4.04 (d, J＝14.70 Hz, 1H, SCH2), 3.57 (s, 3H,
SCH3), 1.50 [d, J＝4.10 Hz, 6H, SCH2C(CH3)2]. HRMS
calcd for C21H22F3N5O6SNa ([M＋Na]＋ ) 552.1135,
found 552.1136.
General synthetic procedure for compounds Va－Vb
The procedure was similar to those of the com-
pounds IIIa－IIIb. Using intermediates IVa－IVb,
3-chloroperoxybenzoic acid (mCPBA) and potassium
carbonate as materials, compounds Va－Vb were ob-
tained.
N2-(1-(S-Methyl-N-(2,2,2-trifluoroacetyl)sulfoni-
midoyl)-2-methylpropan-2-yl)-3-iodo-N1-(3-(trifluoro-
methyl)phenyl)phthalamide (Va) White solid, yield
91.4%, m.p. 77－79 ℃. 1H NMR (400 MHz, DMSO-d6)
δ: 10.64 (s, 1H, Ar-NH), 8.60 (s, 1H, CNH), 8.17 (s, 1H,
Ar-H), 8.04 (d, J＝7.12 Hz, 1H, Ar-H), 7.93 (d, J＝8.10
Hz, 1H, Ar-H), 7.73 (d, J＝7.52 Hz, 1H, Ar-H), 7.58 (t,
J＝8.10 Hz, 1H, Ar-H), 7.47 (d, J＝7.70 Hz, 1H, Ar-H),
7.29 (t, J＝7.72 Hz, 1H, Ar-H), 4.23 (d, J＝14.70 Hz,
1H, SCH2), 4.15 (d, J＝14.70 Hz, 1H, SCH2), 3.67 (s,
3H, SCH3), 1.60 [s, 6H, SCH2C(CH3)2]. HRMS calcd
for C22H20F6IN3O4SNa ([M＋Na]＋) 686.0016, found
686.0016.
Larvicidal activity against oriental armyworm
(Mythimna separate Walker)
The larvicidal activities of the title compounds and
contrast compound flubendiamide against oriental
armyworm were tested according to the leaf-dip method
using the reported procedure.[35] Leaf disks (about 5 cm)
were cut from fresh corn leaves and dipped into the test
solution for 3－5 s. After drying, the treated leaf disks
were placed individually into a glass-surface vessel (7
cm). Each dried treated leaf disk was infested with 10
third-instar oriental armyworm larvae. Percentage mor-
talities were evaluated 4 days after treatment. Leaves
treated with acetone were provided as controls. Each
treatment was performed three times. The insecticidal
activity is summarized in Table 1.
N2-{1-[S-Methyl-N-(2,2,2-trifluoroacetyl)sulfoni-
midoyl]-2-methylpropan-2-yl}-3-nitro-N1-[3-(trifluo-
romethyl)phenyl]phthalamide (Vb)
White solid,
1
yield 82.9%, m.p. 215－216 ℃. H NMR (400 MHz,
DMSO-d6) δ: 10.85 (s, 1H, Ar-NH), 8.79 (s, 1H, CNH),
8.25 (d, J＝7.8 Hz, 1H, Ar-H), 8.17 (s, 1H, Ar-H), 8.07
(d, J＝7.1 Hz, 1H, Ar-H), 7.92 (d, J＝7.4 Hz, 1H,
Ar-H), 7.81 (t, J＝8.10 Hz, 1H, Ar-H), 7.60 (t, J＝7.70
Larvicidal activity against diamondback moth
(Plutella xylostella L.)
The larvicidal activities of the title compounds and
570
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 567—572

Insecticidal Activities of Sulfiliminyl and Sulfoximinyl Phthalic Acid Diamide Structure
Table 1 Insecticidal activities of compounds Ia－Ib, IIa－IIb,
IIIa－IIIb, IVa－IVb, Va－Vb, VIa－VIb and flubendiamide
against oriental armyworm
dride (TFAA) affording N-trifluoroacetylsulfilimines
IVa－IVb. The preparations of their corresponding
N-cyanosulfoximines VIa－VIb were easily achieved
by oxidation of Ia－Ib with m-CPBA under basic con-
dition, as well as Va－Vb by IVa－IVb, IIIa－IIIb by
IIa－IIb. Meanwhile, IIIa－IIIb can also be easily
obtained by VIa－VIb in the presence of TFA. VIa－
VIb were treated with TFAA affording Va－Vb.
Larvicidal activity/% at conc./(mg•L−1)
Compd.
200 100 50
25
10
5
2.5
Ia
100 100 100 100 20
Ib
80
The novel structures of these title compounds have
been characterized by melting point, 1H NMR and
HRMS. All spectral and analytical data were consistent
IIa
60
IIb
50
IIIa
50
1
with the assigned structures. In the H NMR spectra of
IIIb
40
all the title compounds, the proton signals of NHCO on
the amide bridge were observed at δ 10.64－10.89 and
8.43－8.84 as a singlet in DMSO-d6, respectively. Due
to the different chemical environment, the methylene
protons attached to sulfur atom appeared at δ 3.40－
4.23, 3.22－4.15 as a doublet. Meanwhile, the two
methyl protons attached to quaternary carbon in ali-
phatic amide moiety were observed as two singlets as
well.
IVa
100 100 60
50
IVb
Va
100 100 100 100 100 100 40
40
Vb
VIa
100 100 100 100
10
0
VIb
Flubendiamide
100 100 100 100 100
Structure-activity relationship (SAR)
contrast compound flubendiamide against diamondback
moth were tested by the leaf-dip method using the re-
ported procedure.[36,37] Leaf disks (5 cm×3 cm) were
cut from fresh cabbage leaves and then dipped into the
test solution for 3 s. After air-drying, the treated leaf
disks were placed individually into boxes (80 cm). Each
dried treated leaf disk was infested with 30 second-
instar diamondback moths larvae. Percentage mortalities
were evaluated 3 days after treatment. Each treatment
was performed three times. The insecticidal activity is
summarized in Table 2.
Larvicidal activity against oriental armyworm
The larvicidal activities of compounds Ia−Ib, IIa－IIb,
IIIa－IIIb, IVa－IVb, VIa－VIb, VIa－VIb and
flubendiamide (as control) against oriental armyworm
were listed in Table 1. Six kinds of sulfiliminyl and
sulfoximinyl groups were introduced into the aliphatic
amide moiety. On the whole, trifluoromethyl-containing
sulfiliminyl and sulfoximinyl phthalic acid diamide
structures can retain insecticidal activity. Most of the
compounds exist in moderate to good activity against
oriental armyworm, which showed a certain death rate
at 100 mg•L−1. Particularly, three compounds (Ia, Va,
VIa) exhibited 100% larvicidal activities at 25 mg•L−1
against oriental armyworm. It was worth noting that Va
gave high insecticidal activity even at the consideration
of 2.5 mg•L−1, which could be further explored as a lead
compound.
Larvicidal activity against diamondback moth
(Plutella xylostella L.) The larvicidal activities of Ia,
IIIa, Va and flubendiamide as control against dia-
mondback moth were shown in Table 2. From it we can
see that all displayed excellent activities at 5 mg•L−1.
They all showed the same larvicidal activity level at 0.1
mg•L−1, which was lower than that of flubendiamide. To
our delight, IIIa only showed a death rate of 50% at 100
mg•L−1 against oriental armyworm, while IIIa had 14%
death rate at 0.1 mg•L−1 against diamondback moth.
With better solubility and improved hydrophobicity,
N-trifluoroacetylsulfilimine Va showed similar activity
with N-cyanosulfilimine Ia.
Table 2 Insecticidal activities of compounds Ia, IIIa, Va and
flubendiamide against diamondback moth
Larvicidal activity/% at conc./(mg•L−1)
Compd.
5
1
0.1
57
Ia
IIIa
Va
100
100
100
100
86
71
14
100
100
57
100
Flubendiamide
Results and Discussion
In this method of oxidative imination based on a sul-
fide, hypervalent iodinanes such as PhI(OAc)2 was a
mild oxidant with minor byproduct, high yield, and less
time. Cyanogen amine was used as nitrogen source,
which was 1.1 molar equivalents based on the amount
of sulfide. The reaction of the sulfide with cyanogen
amine in the presence of PhI(OAc)2 was carried out in
acetonitrile. The most preferred reaction temperature
ranged from −5 to 0 ℃.
N-Acylaminosulfilimines IIa－IIb were obtained by
N-cyanosulfilimines Ia－Ib in the presence of trifluoro-
acetic acid (TFA) in dichloromethane under ice bath.
While Ia－Ib were treated with trifluoroacetic anhy-
Conclusions
In summary, with introduction of N-cyano, N-tri-
fluoroacetyl, N-carbamoylsulfiliminyl and sulfoximinyl
Chin. J. Chem. 2014, 32, 567—572
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
571

Zhou et al.
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cated that some title compounds exhibited moderate to
good insecticidal activities against oriental armyworm
and diamondback moth. Compound Va showed the best
larvicidal activity against oriental armyworm and dia-
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The present work reported that the new trifluoromethy-
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iminyl moieties are potential lead compounds for further
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Acknowledgement
This work was supported by Syngenta Postgraduate
Fellowship, National Basic Research Program of China
(No. 2010CB126106) and the National Key Technolo-
gies R&D Program (No. 2011BAE06B05).
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 567—572