Design, synthesis, and bioactivity of cyanonitrovinyl neonicotinoids as potential insecticides

Article abstract of DOI:10.1007/s00706-010-0375-4

A series of cyanonitrovinyl neonicotinoids were designed and synthesized via five steps in about 35% overall yields. All compounds were structurally characterized by ¹H nuclear magnetic resonance (NMR), ¹³C NMR, infrared (IR), and high-resolution mass spectrometry (HRMS), and single-crystal X-ray diffraction analysis of 2-[1-[(6-chloropyridin-3-yl)methyl] -2-imidazolidinylidene]-2-nitroacetonitrile revealed that the double bond is (E)-configured. The preliminary agriculture bioassay indicated that one compound exhibited moderate insecticidal activity against pea aphid. Springer-Verlag 2010.

Full text of DOI:10.1007/s00706-010-0375-4

Monatsh Chem (2010) 141:1117–1122
DOI 10.1007/s00706-010-0375-4
ORIGINAL PAPER
Design, synthesis, and bioactivity of cyanonitrovinyl
neonicotinoids as potential insecticides
•
Kewei Wang Xuhong Qian Jingnan Cui
•
Received: 3 February 2010 / Accepted: 4 August 2010 / Published online: 27 August 2010
Ó Springer-Verlag 2010
Abstract A series of cyanonitrovinyl neonicotinoids
were designed and synthesized via five steps in about 35%
overall yields. All compounds were structurally charac-
terized by 1H nuclear magnetic resonance (NMR), 13C
NMR, infrared (IR), and high-resolution mass spectrometry
(HRMS), and single-crystal X-ray diffraction analysis of
2-[1-[(6-chloropyridin-3-yl)methyl]-2-imidazolidinylidene]-
2-nitroacetonitrile revealed that the double bond is (E)-
configured. The preliminary agriculture bioassay indicated
that one compound exhibited moderate insecticidal activity
against pea aphid.
effective solution to this problem is to find novel neonicot-
inoids with higher insecticidal activity and higher nAChR
binding affinity. Compared with imidacloprid, the nitrovinyl
neonicotinoid 6-Cl-1-(pyridin-3-yl-methyl)-2-nitromethy-
leneimidazolidine (PMNI) has similar insecticidal activity
and higher binding affinity [6], but 6-Cl-PMNI has never
been commercialized because of its photolability [7].
Strong electron-withdrawing groups, such as nitro or
cyano groups, play a crucial role in binding of neonicoti-
noids to nAChR [8–10], and high affinity confers them
with high activity [11]. Kagabu et al. [12] reported that
compound 2 with two cyano groups had higher activity
than compound 1 with one cyano group. Therefore, it could
be presumed that compound 3a with nitro and cyano
groups would have higher binding affinity and activity than
6-Cl-PMNI, in which there is only one electron-with-
drawing group. Qian et al. [13, 14] reported that
photostability was improved if the hydrogen atom of
=CHNO2 in 6-Cl-PMNI was replaced by another group. It
is presumed that 3a would have higher photostability than
6-Cl-PMNI. In addition, replacement of the chloropyridine
ring by different heterocycles (Het) could adjust its lipo-
philicity (Scheme 1). Herein, we report the synthesis and
bioactivity of the cyanonitrovinyl neonicotinoids 3.
Keywords Neonicotinoids Á Insecticides Á
(E)-configuration Á Nitrovinyl compound Á X-ray analysis
Introduction
Neonicotinoids, acting on insect nicotinic acetylcholine
receptor (nAChR) [1, 2], are the major class of insecticides
used throughout the world for crop protection. The first ne-
onicotinoid, imidacloprid, was introduced to the market in
1991 (Fig. 1) [3], and in recent years monitoring results have
revealed signs of resistance to it in some regions [4, 5]. One
Results and discussion
K. Wang Á J. Cui (&)
State Key Laboratory of Fine Chemicals,
Dalian University of Technology,
PO Box 89, Zhongshan Road 158,
Dalian 116012, China
Synthesis of arylmethyl cyanonitrovinyl imidazolines 3
Starting from ethylenediamine, compounds 6 were syn-
thesized in 56% yield according to the procedure reported
previously [15]. Reaction of 6 with benzoyl isothiocyanate
proceeded readily at room temperature to give 7 in 85%
yield, and further oxidation of 7 with bromine gave 8 in
e-mail: jncui@dlut.edu.cn
X. Qian
Shanghai Key Laboratory of Chemical Biology, School of
Pharmacy, East China University of Science and Technology,
PO Box 544, 130 Meilong Road, Shanghai 200237, China
123

1118
K. Wang et al.
X = N, R1 = -, R2 = NO2
Cl
Imidacloprid:
N
NaOCH3
CH3OH
N
NH
6-Cl-PMNI: X = C, R1 = H, R2 = NO2
MeO
N
S
3b
N
NH
R2
X = C, R1 = H, R2 = CN
1:
NC
NO2
X = C, R1 = CN, R2 = CN
3a: X = C, R1 = CN, R2 = NO2
2:
X
3h
R1
Scheme 2
Fig. 1 Structure of neonicotinoids
94% yield. Compound 8 was subjected to fragmentation
reaction, initiated by base and culminating in extrusion of
sulfur with concomitant formation of 3 in 80% yield [16]
(Scheme 1). The overall yield of the five steps of 36%
based on ethylenediamine was similar to in previous
reports [15, 16].
NO2
CN
H
N
The synthesis of 3h was different from 3a–3g
(Scheme 2). When the amount of sodium methoxide was
two equivalents of 8b, the final product was 3h. When the
amount of sodium methoxide was equivalent to 8b, the
final product was 3b. This indicated that the formation of
3h by substitution of chloride with methoxy group pro-
ceeded after the formation of 3b.
N
N
Cl
Confirmation of configuration
The C=C double bond in compound 3 will lead to geo-
metrical isomerism. To confirm its configuration, single-
crystal X-ray diffraction analysis of 3a was performed,
which showed that 3a is the (E)-diastereomer (Fig. 2).
Fig. 2 X-ray single-crystal structure of 3a
Table 1 Insecticidal activity of 3a at different concentrations against
pea aphid
Biological activity
Compound
Mortality (%)
500 ppm
Insecticidal activity of compounds 3 against pea aphid was
tested. Only 3a exhibited moderate activity, with 100%
mortality at 500 ppm (Table 1), indicating that the chlo-
ropyridine is indispensable. Compared with 6-Cl-PMNI,
compound 3a had lower insecticidal activity. One possible
150 ppm
30 ppm
5 ppm
3a
100
100
89.4
100
63.4
100
0
6-Cl-PMNI
81.0
Scheme 1
O
NO2
Het
MeS
NCS
NH2
Het
H2N
N
NH
MeS
NH2
N
H
Het
Cl
N
CH3CN
CH3CN
C2H5OH
NO2
4a-4g
5a-5g
6a-6g
Het
N
N
Het
NH
S
N
Br2
CH3COOH
NH
Het
N
NaOCH3
CH3OH
H
O
N
O2N
O2N
NO2
NC
S
O
7a-7g
8a-8g
3a-3h
Cl
S
a: Het =
e: Het =
b: Het =
f: Het =
c: Het =
g: Het =
d: Het =
Cl
N
N
N
N
OCH3
S
h: Het =
N
O
S
123

Design, synthesis, and bioactivity of cyanonitrovinyl neonicotinoids
1119
(Z)-N-[2-[1-[(6-Chloropyridin-3-yl)methyl]-2-
imidazolidinylidene]-2-nitrothioacetyl]benzamide
(7a, C18H16N5O3SCl)
reason was that, in comparison with 6-Cl-PMNI, 3a had
lower lipophilicity because of the introduction of a cyano
group instead of hydrogen. The low lipophilicity of 3a
made it difficult for it to diffuse through the insect’s lipo-
philic cuticle to the site of action [17]. Additionally, in the
single-crystal structure of 3a, torsion angles of 6.5°
between amidine and nitro group and 14.8° between ami-
dine and cyano group were found. In 6-Cl-PMNI, the
torsion angle between amidine and nitro group is about
0.6°. Coplanarity between amidine and nitro group was
considered to be an essential feature for high affinity. The
lack of coplanarity in compound 3a could also be associ-
ated with the lower activity of 3a [8, 11].
Yield 85%; red powder; m.p.: 140.1–142.0 °C; IR (KBr):
m = 3,432, 1,591, 1,579, 1,141 cm-1; 1H NMR (400 MHz,
ꢀ
DMSO-d6): d = 14.02 (s, 1H), 10.35 (s, 1H), 8.42 (s, 1H),
7.91 (d, 5H, J = 7.6 Hz), 7.84 (dd, 1H, J = 8.4 Hz,
J = 2.4 Hz), 7.69–7.56 (m, 4H), 4.58 (s, 2H), 3.91–3.81
(m, 4H) ppm; HRMS (ESI): calculated for C18H16N5O3NaS-
Cl [M ? Na?] 440.0560, found 440.0580.
(Z)-N-[2-[1-[(2-Chlorothiazol-5-yl)methyl]-2-imidazolid-
inylidene]-2-nitrothioacetyl]benzamide
(7b, C16H14N5O3S2Cl)
Inconclusion, wehavedesignedand synthesized a seriesof
novel cyanonitrovinyl neonicotinoids with nitro in (E)-con-
figuration. Bioactivity results showed that 3a exhibited
moderate insecticidal activity against pea aphid. A possible
explanation for the decrease in its insecticidal activity com-
pared with 6-Cl-PMNI is the effect of its lower lipophilicity.
Further work is in progress to improve its lipophilicity to
design more active neonicotinoid insecticides.
Yield 88%; red powder; m.p.: 125.4–126.9 °C; IR (KBr):
m = 3,438, 1,586, 1,572, 1,139 cm-1; 1H NMR (400 MHz,
ꢀ
DMSO-d6): d = 14.00 (s, 1H), 10.38 (s, 1H), 7.92 (d, 2H,
J = 7.6 Hz), 7.69–7.59 (m, 4H), 4.79 (s, 2H), 3.95–3.83 (m,
4H) ppm; HRMS (ESI): calculated for C16H14N5O3NaS2Cl
[M ? Na?] 446.0124, found 446.0123.
(Z)-N-[2-Nitro-2-[1-(2-pyridinylmethyl)-2-imidazolidiny-
lidene]thioacetyl]benzamide (7c, C18H17N5O3S)
Yield 83%; red powder; m.p.: 131.8–133.1 °C; IR (KBr):
m = 3,431, 1,587, 1,567, 1,139 cm-1; 1H NMR (400 MHz,
ꢀ
Experimental
DMSO-d6): d = 14.00 (s, 1H), 10.45 (s, 1H), 8.71 (d, 1H,
J = 4.4 Hz), 8.28–8.0 (m, 3H), 7.95–7.62 (m, 5H), 4.70 (s,
2H), 3.94–3.88 (m, 4H) ppm; HRMS (ESI): calculated for
C18H17N5O3NaS [M ? Na?] 406.0950, found 406.0946.
Melting points were obtained with an X-6 micro-melting
point apparatus and are reported corrected. Infrared (IR)
spectra were recorded on a Nicolet 20DXB Fourier-trans-
form (FT)-IR spectrometer using potassium bromide
pellets or films. 1H NMR spectra were obtained on a Varian
INOVA 400-MHz NMR spectrometer with dimethyl sulf-
oxide (DMSO)-d6 as solvent and tetramethylsilane (TMS)
as internal standard. High-resolution mass spectra (HRMS)
were obtained on HPLC-Q-Tof MS (Micro) spectrometer.
X-ray single-crystal diffraction experiments were carried
out on a Bruker Smart APEXII diffractometer at 25 °C. All
solvents were of analytic grade. All chemicals and reagents
were purchased from commercial suppliers. Nitrovinyl
imidazolidines 6 were synthesized according to the pro-
cedure reported previously [15].
(Z)-N-[2-Nitro-2-[1-(3-pyridinylmethyl)-2-imidazolidiny-
lidene]thioacetyl]benzamide (7d, C18H17N5O3S)
Yield 87%; red powder; m.p.: 136.1–137.4 °C; IR (KBr):
m = 3,441, 1,584, 1,574, 1,134 cm-1; 1H NMR (400 MHz,
ꢀ
DMSO-d6): d = 14.01 (s, 1H), 10.40 (s, 1H), 8.77 (s, 2H),
8.24 (d, 1H, J = 4.0 Hz), 7.90 (d, 2H, J = 7.6 Hz), 7.83 (t,
1H, J = 7.6 Hz), 7.68 (t, 1H, J = 7.2 Hz), 7.60 (d, 2H,
J = 7.2 Hz), 4.70 (s, 2H), 3.90–3.85 (m, 4H) ppm; HRMS
(ESI): calculated for C18H17N5O3NaS [M ? Na?]
406.0950, found 406.0955.
(Z)-N-[2-Nitro-2-[1-(phenylmethyl)-2-imidazolidiny-
lidene]thioacetyl]benzamide (7e, C19H18N4O3S)
Yield 85%; red powder; m.p.: 157.1–158.8 °C; IR (KBr):
m = 3,437, 1,589, 1,570, 1,128 cm-1; 1H NMR (400 MHz,
General synthesis procedure for 7
ꢀ
DMSO-d6): d = 14.06 (s, 1H), 10.22 (s, 1H), 7.91 (d, 2H,
J = 7.2 Hz), 7.67 (t, 1H, J = 7.6 Hz), 7.59 (t, 2H,
J = 7.6 Hz), 7.39–7.32 (m, 5H), 4.49 (s, 2H), 3.92–3.74
(m, 4H) ppm; HRMS (ESI): calculated for C19H18N4O3-
NaS [M ? Na?] 405.0997, found 405.0997.
Benzoyl chloride (0.43 g, 3 mmol) in 5 cm3 acetonitrile
was added dropwise to freshly prepared solution of 0.24 g
ammonium thiocyanate (3.1 mmol) in 10 cm3 acetonitrile,
which was refluxed for 30 min and cooled to room tem-
perature, and the solid was filtered off. The filtrate was
added dropwise to solution of 0.76 g 6a (3 mmol) in
20 cm3 acetonitrile and stirred at room temperature for 4 h.
The suspension was filtered to give 1.09 g 7a (85% yield).
Compounds 7b–7g were prepared similarly.
(Z)-N-[2-[1-(2-Furanylmethyl)-2-imidazolidinylidene]-
2-nitrothioacetyl]benzamide (7f, C17H16N4O4S)
Yield 86%; red powder; m.p.: 128.3–129.9 °C; IR (KBr):
m = 3,434, 1,589, 1,577, 1,137 cm-1; 1H NMR (400 MHz,
ꢀ
123

1120
K. Wang et al.
DMSO-d6): d = 14.05 (s, 1H), 10.26 (s, 1H), 7.92 (d, 2H,
J = 7.6 Hz), 7.66 (d, 2H, J = 7.2 Hz), 7.60 (t, 2H,
J = 7.2 Hz), 6.44 (s, 2H), 4.52 (s, 2H), 3.89–3.78 (m,
4H) ppm; HRMS (ESI): calculated for C17H16N4O4NaS
[M ? Na?] 395.0790, found 395.0788.
(Z)-N-[2,3-Dihydro-7-nitro-1-(3-pyridinylmethyl)-
1H-imidazo[1,2-b]isothiazol-6-ylidene]benzamide
(8d, C18H16N5O3S)
Yield 92%; light-red powder; m.p.: 235.0–236.9 °C; IR
-1
ꢀ
(KBr): m = 1,591, 1,573 cm
;
1H NMR (400 MHz,
DMSO-d6): d = 8.95 (s, 1H), 8.84 (d, 1H, J = 4.2 Hz),
8.50 (d, 1H, J = 8.0 Hz), 8.23 (d, 2H, J = 7.2 Hz), 8.00
(d, 1H, J = 7.2 Hz), 7.65–7.54 (m, 3H), 4.99 (s, 2H), 4.14
(s, 4H) ppm; HRMS (ESI): calculated for C18H16N5O3S
[M ? H?] 382.0974, found 382.0980.
(Z)-N-[2-Nitro-2-[1-(2-thienylmethyl)-2-imidazolidiny-
lidene]thioacetyl]benzamide (7g, C17H16N4O3S2)
Yield 88%; red powder; m.p.: 168.5–169.4 °C; IR (KBr):
m = 3,442, 1,588, 1,567, 1,138 cm-1; 1H NMR (400 MHz,
ꢀ
DMSO-d6): d = 14.26 (s, 1H), 9.94 (s, 1H), 7.92 (d, 2H,
J = 7.6 Hz), 7.67 (t, 1H, J = 7.2 Hz), 7.59 (t, 2H,
J = 7.6 Hz), 7.54 (t, 1H, J = 7.6 Hz), 7.16–7.15 (m,
2H), 4.70 (s, 2H), 3.83–3.73 (m, 4H) ppm; HRMS (ESI):
calculated for C17H16N4O3NaS2 [M ? Na?] 411.0718,
found 411.0722.
(Z)-N-[2,3-Dihydro-7-nitro-1-(phenylmethyl)-1H-imidazo-
[1,2-b]isothiazol-6-ylidene]benzamide
(8e, C19H16N4O3S)
Yield 95%; light-red powder; m.p.: 204.3–205.9 °C; IR
-1
ꢀ
(KBr): m = 1,599, 1,572 cm
;
1H NMR (400 MHz,
DMSO-d6): d = 8.22 (d, 2H, J = 7.2 Hz), 7.64–7.53 (m,
3H), 7.41–7.30 (m, 5H), 4.81 (s, 2H), 4.07 (s, 4H) ppm;
HRMS (ESI): calculated for C19H16N4O3NaS [M ? Na?]
403.0841, found 403.0845.
General synthesis procedure for 8
To astirred solution of 1.00 g 7a (2.4 mmol) in 10 cm3 warm
acetic acid was added dropwise 0.43 g bromine (2.6 mmol)
in 2 cm3 acetic acid, with stirring for 10 min. The solvent
was removed by evaporation under reduced pressure, and the
residue was washed with water to afford 0.94 g 8a (94%
yield). Compounds 8b–8g were prepared similarly.
(Z)-N-[1-(2-Furanylmethyl)-2,3-dihydro-7-nitro-
1H-imidazo[1,2-b]isothiazol-6-ylidene]benzamide
(8f, C17H14N4O4S)
Yield 97%; light-red powder; m.p.: 200.6–202.4 °C; IR
-1
ꢀ
(KBr): m = 1,603, 1,575 cm
;
1H NMR (400 MHz,
(Z)-N-[1-[(6-Chloropyridin-3-yl)methyl]-2,3-dihydro-7-
nitro-1H-imidazo[1,2-b]isothiazol-6-ylidene]benzamide
(8a, C18H14N5O3SCl)
DMSO-d6): d = 7.92 (d, 1H, J = 7.6 Hz), 7.67–7.58 (m,
4H), 6.45 (s, 2H), 4.52 (s, 2H), 3.89 (s, 4H) ppm; HRMS
(ESI): calculated for C17H14N4O4NaS [M ? Na?]
393.07558, found 393.0768.
Yield 94%; light-red powder; m.p.: 229.1–231.0 °C; IR
-1
ꢀ
(KBr): m = 1,605, 1,577 cm
;
1H NMR (400 MHz,
(Z)-N-[2,3-Dihydro-7-nitro-1-(2-thienylmethyl)-
1H-imidazo[1,2-b]isothiazol-6-ylidene]benzamide
(8g, C17H14N4O3S2)
DMSO-d6): d = 8.40 (d, 1H, J = 1.6 Hz), 8.23 (d, 2H,
J = 7.2 Hz), 7.91–7.53 (m, 5H) 4.84 (s, 2H), 4.09
(s, 4H) ppm; HRMS (ESI): calculated for C18H14N5O3NaS-
Cl [M ? Na?] 438.0404, found 438.0405.
Yield 96%; light-red powder; m.p.: 198.7–200.3 °C; IR
-1
ꢀ
(KBr): m = 1,608, 1,565 cm
;
1H NMR (400 MHz,
(Z)-N-[1-[(2-Chlorothiazol-5-yl)methyl]-2,3-dihydro-7-
nitro-1H-imidazo[1,2-b]isothiazol-6-ylidene]benzamide
(8b, C16H12N5O3S2Cl)
DMSO-d6): d = 8.25 (d, 2H, J = 6.0 Hz), 7.64–7.52 (m,
4H), 7.11–7.02 (m, 2H), 5.00 (s, 2H), 4.10 (s, 4H) ppm;
HRMS (ESI): calculated for C17H14N4O3NaS2 [M ? Na?]
409.0405, found 409.0400.
Yield 96%; light-red powder; m.p.: 215.4–216.8 °C; IR
-1
ꢀ
(KBr): m = 1,602, 1,571 cm
;
1H NMR (400 MHz,
DMSO-d6): d = 8.24 (d, 2H, J = 7.6 Hz), 7.74 (s, 1H),
7.65–7.54 (m, 3H) 4.99 (s, 2H), 4.09 (s, 4H) ppm; HRMS
(ESI): calculated for C16H12N5O3NaS2Cl [M ? Na?]
443.9968, found 443.9965.
General synthesis procedure for 3
To compound 8a (0.83 g, 2 mmol) in 20 cm3 methanol
was added 0.11 g sodium methoxide (2.1 mmol), with
reflux for 10 min. The solvent was evaporated in vacuo,
and the residue was washed with water and diethyl ether to
afford 0.44 g 3a (80% yield). Compounds 3b–3g were
prepared similarly.
(Z)-N-[2,3-Dihydro-7-nitro-1-(2-pyridinylmethyl)-
1H-imidazo[1,2-b]isothiazol-6-ylidene]benzamide
(8c, C18H16N5O3S)
Yield 95%; light-red powder; m.p.: 243.7–245.5 °C; IR
-1
ꢀ
(KBr): m = 1,597, 1,572 cm
;
1H NMR (400 MHz,
(E)-2-[1-[(6-Chloropyridin-3-yl)methyl]-2-
imidazolidinylidene]-2-nitroacetonitrile
(3a, C11H10ClN5O2)
DMSO-d6): d = 8.73 (d, 1H, J = 4.2 Hz), 8.31–8.22 (m,
3H), 7.87–7.53 (m, 5H), 5.10 (s, 2H), 4.15 (s, 4H) ppm;
HRMS (ESI): calculated for C18H16N5O3S [M ? H?]
382.0974, found 382.0978.
Yield 78%; light-yellow powder; m.p.: 174.8–175.9 °C; IR
(KBr): m = 2,213, 1,544, 1,325 cm-1; 1H NMR (400 MHz,
ꢀ
123

Design, synthesis, and bioactivity of cyanonitrovinyl neonicotinoids
1121
DMSO-d6): d = 9.49 (br, 1H), 8.40 (d, 1H, J = 2.4 Hz),
7.83 (dd, 1H, J = 2.4 Hz, J = 8.0 Hz), 7.56 (d, 1H,
J = 8.0 Hz), 4.80 (s, 2H), 3.71 (s, 4H) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 158.9, 149.8, 149.0, 139.0,
131.3, 124.5, 115.2, 90.5, 50.0, 48.3, 42.6 ppm; HRMS
(ESI): calculated for C11H10ClN5NaO2 [M ? Na?]
302.0421, found 302.0410.
DMSO-d6): d = 9.44 (br, 1H), 7.69 (d, 1H, J = 0.8 Hz),
6.49–6.46 (m, 2H), 4.79 (s, 2H), 3.76–3.63 (m, 4H) ppm;
13C NMR (100 MHz, DMSO-d6): d = 158.5, 148.9, 144.1,
115.5, 111.1, 109.9, 91.0, 50.0, 43.9, 42.5 ppm; HRMS
(ESI): calculated for C10H10N4NaO3 [M ? Na?] 257.0651,
found 257.0644.
(E)-2-Nitro-2-[1-(2-thienylmethyl)-2-imidazolidiny-
lidene]acetonitrile (3g, C10H10N4O2S)
(E)-2-[1-[(2-Chlorothiazol-5-yl)methyl]-2-imidazolidiny-
lidene]-2-nitroacetonitrile (3b, C9H8ClN5O2S)
Yield 76%; light-yellow powder; m.p.: 165.5–167.1 °C; IR
(KBr): m = 2,209, 1,550, 1,332 cm-1; 1H NMR (400 MHz,
ꢀ
Yield 75%; yellow powder; m.p.: 178.9–180.3 °C; IR
(KBr): m = 2,206, 1,542, 1,343 cm-1; 1H NMR (400 MHz,
DMSO-d6): d = 9.38 (br, 1H), 7.55 (dd, 1H, J = 1.2 Hz,
J = 5.2 Hz), 7.15 (d, 1H, J = 6.4 Hz), 7.04 (t, 1H,
J = 3.2 Hz), 4.95 (s, 2H), 3.75–3.63 (m, 4H) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 163.1, 142.2, 133.4,
132.3, 132.1, 120.2, 95.6, 54.3, 50.6, 47.3 ppm; HRMS
(ESI) calculated for C10H10N4NaO2S [M ? Na?]
273.0422, found 273.0419.
ꢀ
DMSO-d6): d = 9.59 (br, 1H), 7.73 (s, 1H), 4.88 (s, 2H),
3.67 (s, 4H) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 158.4, 141.7, 135.6, 123.9, 115.6, 90.5, 59.1, 49.5,
42.6 ppm; HRMS (ESI): calculated for C9H8ClN5NaO2S
[M ? Na?] 307.9985, found 307.9996.
(E)-2-Nitro-2-[1-(2-pyridinylmethyl)-2-imidazolidiny-
lidene]acetonitrile (3c, C11H11N5O2)
(E)-2-[1-[(2-Methoxythiazol-5-yl)methyl]-2-imidazolidiny-
lidene]-2-nitroacetonitrile (3h, C10H11N5O3S)
To compound 8b (0.84 g, 2 mmol) in 20 cm3 methanol was
added 0.26 g sodium methoxide (4.8 mmol), with reflux for
10 min. The solvent was evaporated, and the residue was
washed with water and diethyl ether to afford 0.45 g 3h (79%
yield). Light-yellow powder; m.p.: 169.4–170.8 °C; IR
1H NMR
ꢀ
Yield 70%; light-yellow powder; m.p.: 174.1–175.9 °C; IR
(KBr): m = 2,210, 1,544, 1,359 cm-1; 1H NMR (400 MHz,
ꢀ
DMSO-d6): d = 9.46 (br, 1H), 8.54 (d, 1H, J = 4.4 Hz),
7.82 (t, 1H, J = 6.8 Hz), 7.37 (d, 1H, J = 8.0 Hz), 7.33
(t, 1H, J = 6.8 Hz), 4.92 (s, 2H), 3.83–3.69 (m, 4H) ppm;
13C NMR (100 MHz, DMSO-d6): d = 159.3, 155.4, 149.8,
137.6, 123.2, 122.1, 115.3, 91.1, 51.7, 50.9, 42.6 ppm;
HRMS (ESI): calculated for C11H11N5NaO2 [M ? Na?]
268.0810, found 268.0818.
(KBr): m = 2,205, 1,538, 1,341 cm-1
;
(400 MHz, DMSO-d6): d = 9.47 (br, 1H), 7.24 (s, 1H),
4.81 (s, 2H), 4.01 (s, 3H), 3.73–3.64 (m, 4H) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 175.4, 158.4, 137.7, 123.9,
115.7, 90.6, 59.0, 49.4, 44.4, 42.7 ppm; HRMS (ESI):
calculated for C10H11N5NaO3S [M ? Na?] 304.0480,
found 304.0485.
(E)-2-Nitro-2-[1-(3-pyridinylmethyl)-2-imidazolidiny-
lidene]acetonitrile (3d, C11H11N5O2)
Yield 72%; light-yellow powder; m.p.: 172.4–173.8 °C; IR
(KBr): m = 2,205, 1,548, 1,340 cm-1; 1H NMR (400 MHz,
ꢀ
DMSO-d6): d = 9.47 (br, 1H), 8.55 (s, 2H), 7.75 (d, 1H,
J = 7.2 Hz), 7.43 (t, 1H, J = 7.2 Hz), 4.82 (s, 2H), 3.71 (s,
4H) ppm; 13C NMR (100 MHz, DMSO-d6): d = 158.9,
149.4, 149.0, 135.5, 131.6, 124.1, 115.4, 90.7, 50.2, 48.9,
42.6 ppm; HRMS (ESI): calculated for C11H11N5NaO2
[M ? Na?] 268.0810, found 268.0817.
X-ray data for 3a
C11H10ClN5O2, unit cell parameters: a = 11.7507(4),
b = 9.0996(14), c = 10.9721(17), a = 90.00, b = 90.00,
c = 90.00, space group Pbca. The crystallographic data for
the structure 3a reported in this paper have been deposited
with the Cambridge Crystallographic Data Center as sup-
plementary publication No. CCDC 747419 for compound
3a. Copies of the data can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK (fax: ?44-1223-336033; email: deposit@ccdc.
cam.ac.uk).
(E)-2-Nitro-2-[1-(phenylmethyl)-2-imidazolidinylidene]-
acetonitrile (3e, C12H12N4O2)
Yield 75%; light-yellow powder; m.p.: 167.9–169.8 °C; IR
(KBr): m = 2,207, 1,542, 1,338 cm-1; 1H NMR (400 MHz,
ꢀ
DMSO-d6): d = 9.47 (br, 1H), 7.39–7.31 (m, 5H), 4.76 (s,
2H), 3.66 (s, 4H) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 158.1, 135.2, 128.7, 127.7, 127.2, 114.9, 90.3,
50.4, 49.5, 42.0 ppm; HRMS (ESI): calculated for
C12H12N4NaO2 [M ? Na?] 267.0858, found 267.0868.
Bioassay
All bioassays were performed on representative test organ-
isms reared in the laboratory. The bioassay was repeated at
25 1 °C according to statistical requirements. All com-
pounds were dissolved in N,N-dimethylformamide (AP,
Shanghai Chemical Reagent Co., Ltd., Shanghai, China) and
(E)-2-[1-(2-Furanylmethyl)-2-imidazolidinylidene]-2-
nitroacetonitrile (3f, C10H10N4O3)
Yield 74%; light-yellow powder; m.p.: 164.9–166.8 °C; IR
(KBr): m = 2,208, 1,548, 1,355 cm-1; 1H NMR (400 MHz,
ꢀ
123

1122
K. Wang et al.
2. Nishimura K, Kanda Y, Okazawa A, Ueno T (1994) Pestic
Biochem Physiol 50:51
3. Casida JE, Quistad GB (1998) Annu Rev Entomol 43:1
4. Cahill M, Gorman K, Day S, Denholm I, Elbert A, Nauen R
(1996) Bull Entomol Res 86:343
5. Elbert A, Nauen R, Cahill M, Devonshire AL, Scarr AW, Sone S,
Steffens R (1996) Pflanzenschutz-Nachrichten Bayer 49:5
6. Kagabu S, Nishiwaki H, Sato K, Hibi M, Yamaoka N, Nakagawa
Y (2002) Pest Manag Sci 58:483
diluted with distilled water containing Triton X-100
(0.1 mg dm-3) to obtain series concentrations of 500.0,
250.0, and 125.0 mg dm-3 and others for bioassays. For
comparative purposes, 6-Cl-PMNI was tested under the
same conditions.
Insecticidal test for cowpea aphid (Aphis craccivora)
7. Kagabu S, Medej S (1995) Biosci Biotech Biochem 59:980
8. Tomizawa M, Lee DL, Casida JE (2000) J Agric Food Chem
48:6016
9. Matsuda K, Shimomura M, Ihara M, Akamatsu M, Sattelle DB
(2005) Biosci Biotech Biochem 69:1442
10. Wang YL, Cheng JG, Qian XH, Li Z (2007) Bioorg Med Chem
15:2624
11. Tomizawa M, Zhang N, Kathleen A, Durkin MM, Casida JE
(2003) Biochemistry 42:7819
12. Moriya K, Shibuya K, Hattori Y, Tsuboi S, Shiokawa K, Kagabu
S (1992) Biosci Biotech Biochem 56:364
13. Shao XS, Zhang WW, Peng Y, Li Z, Tian ZZ, Qian XH (2008)
Bioorg Med Chem Lett 18:6513
14. Shao XS, Li Z, Qian XH, Xu XY (2009) J Agric Food Chem
57:951
15. Kagabu S, Moriya K, Shibuya K, Hattori Y, Tsuboi S, Shiokawa
K (1992) Biosci Biotech Biochem 56:362
Activities of insecticidal compounds against cowpea aphid
were tested by the leaf-dip method according to our previ-
ously reported procedure [14]. Horsebean plant leaves with
40–60 apterous adults were dipped into diluted solutions of
the chemicals containing Triton X-100 (0.1 mg dm-3) for
5 s, and the excess dilution was sucked out with filter paper;
the burgeons were placed in the conditioned room
[25 1 °C, 50% relative humidity (RH)]. Water containing
Triton X-100 (0.1 mg dm-3) was used as control. Mortality
rates were evaluated 24 h after treatment. Each treatment
had three repetitions, and data were adjusted and subjected to
probit analysis as before.
16. Rajappa S, Advani BG, Sreenvasan R (1977) Tetrahedron
33:1057
17. Yamamoto I, Tomizawa M, Satio T, Miyamoto T, Walcott EC,
Sumikawa W (1998) Arch Insect Biochem Physiol 37:24
Acknowledgments We are grateful to the National Natural Science
Foundation of China (90713030; 20876025) and the National Basic
Research Program of China (grant No. 2009CB724706).
References
1. Bai D, Lummis SCR, Leicht W, Breer H, Sattelle DB (1991)
Pestic Sci 33:197
123