Design, synthesis, and insecticidal activities of novel analogues of neonicotinoids: Replacement of nitromethylene with nitroconjugated system

Article abstract of DOI:10.1021/jf803305f

To replace nitromethylene pharmacophore with a nitroconjugated system, a series of novel neonicotinoid analogues bearing five-membered aromatic heterocycles were designed and synthesized. Bioassays indicated that some of the synthesized compounds exhibited higher insecticidal activities than imidacloprid against cowpea aphids (Aphis craccivora), armyworm (Pseudaletia separate Walker), Nephotettix bipunctatus (Fabricius), and small brown rice planthopper (Laodelphasx striatellus). Exhilaratingly, the activity levels of derivatives 13a and 13j rivaled that of imidacloprid.

Full text of DOI:10.1021/jf803305f

J. Agric. Food Chem. 2009, 57, 951–957 951
Design, Synthesis, and Insecticidal Activities of
Novel Analogues of Neonicotinoids: Replacement of
Nitromethylene with Nitroconjugated System
XUSHENG SHAO, ZHONG LI,* XUHONG QIAN, AND XIAOYONG XU*
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of
Science and Technology, Shanghai 200237, China
To replace nitromethylene pharmacophore with a nitroconjugated system, a series of novel
neonicotinoid analogues bearing five-membered aromatic heterocycles were designed and synthe-
sized. Bioassays indicated that some of the synthesized compounds exhibited higher insecticidal
activities than imidacloprid against cowpea aphids (Aphis craccivora), armyworm (Pseudaletia separate
Walker), Nephotettix bipunctatus (Fabricius), and small brown rice planthopper (Laodelphasx
striatellus). Exhilaratingly, the activity levels of derivatives 13a and 13j rivaled that of imidacloprid.
KEYWORDS: Neonicotinoids; nitromethylene; imidacloprid; insecticide
INTRODUCTION
action; it can stabilize the planarity of the pharmacophore and
form a conjugation system that facilitates electron flow toward
the nitro group (20-22). Furthermore, all of the commercialized
neonicotinoids have a CdN or CdC double bond, so it is
believed that the double bond is indispensable to this kind of
compound. Interestingly, N-((6-chloropyridin-3-yl)methyl)-3-
(dimethylamino)-N,N′-dimethyl-2-nitroacrylamidine (5) discov-
ered by Dow Agrosciences (23), into which the conjugated
double bond was introduced, also showed high insecticidal
activities. This special structure feature revealed that replacement
of the double bond by a conjugated system might be the tactic
to obtain novel analogues with high activities.
Neonicotinoids, targeting insect nicotinic acetylcholine recep-
tors (nAChRs) (1, 2), have attracted considerable attention for
decades and represent a new generation of synthetic insecticides
as they combine unique properties allowing them to be the
fastest growing synthetic insecticides on the market (3). Some
of these unique properties are a broad-spectrum insecticidal
activity, low application rate, novel mode of action, and
favorable safety profile; as well, they lack cross-resistance to
other insecticides (4, 5). Imidacloprid (1), the first commercial-
ized neonicotinoid, has the largest sales of any insecticide
worldwide (6). Neonicotinoids are increasingly used in crop
protection and animal health care due to the decrease in
effectiveness of organophosphorus and carbamate derivatives.
However, significant increases in resistance were observed in a
range of species after frequent field applications (7-14).
Therefore, the development of neonicotinoids with new chemical
structures and high insecticidal activities is highly desirable.
According to the chemical structures of neonicotinoids
developed in the past several decades, the common molecular
structural features of neonicotinoids consist of four sections:
(1) aromatic heterocycle, (2) flexible linkage, (3) hydrohetero-
cyles or guanidine/amidine, and (4) electron-withdrawing seg-
ment (Scheme 1) (15). A major emphasis on searching for new
neonicotinoids has involved the modification of the electron-
withdrawing segment CdX. It has been proved that nitrometh-
ylene is one of the most effective electron-withdrawing seg-
ments, and neonicotinoids bearing this scaffold are called
“nitromethylene neonicotinoids”, such as 6-Cl-PMNI (2), ni-
tenpyram (3), and compound 4 (16-19). The double bond in
the nitromethylene group plays a crucial role in its modes of
In a previous study, we found that 6-Cl-PMNI could react
with R,ꢀ-unsaturated aldehydes to give nitromethylene com-
pounds 7 with high insecticidal activities (15, 24), but when
* Corresponding authors [telephone + 86 21 64253540; fax +86
21 64252603; e-mail (Z.L.) lizhong@ecust.edu.cn, (X.X.) xyxu@
ecust.edu.cn].
Figure 1. Structures of imidacloprid, nitromethylene neonicotinoids, and
neonicotinoids with nitroconjugated system.
10.1021/jf803305f CCC: $40.75  2009 American Chemical Society
Published on Web 01/12/2009

952 J. Agric. Food Chem., Vol. 57, No. 3, 2009
Scheme 1. General Structure of Neonicotinoids
Shao et al.
1H), 4.78 (d, J ) 15.6 Hz, 1H), 4.67 (d, J ) 15.6 Hz, 1H), 4.08-4.18
(m, 4H); 13C NMR (100 Mz, DMSO-d6) δ 158.7, 153.2, 150.7, 150.3,
144.9, 140.3, 131.1, 129.7, 129.5, 126.2, 124.7, 115.6, 49.7, 46.9, 44.5;
HRMS (ES+) calcd for C15H14N4O335Cl (M + H)+, 333.0754; found,
333.0761; calcd for C15H14N4O337Cl (M + H)+, 335.0725; found,
335.0766. Anal. Calcd for C15H14N4O3Cl2: C, 48.80; H, 3.82; N, 15.18.
Found: C, 48.08; H, 3.51; N, 15.47.
(Z)-2-Chloro-5-((2-(2-(5-methylfuran-2-yl)-1-nitroVinyl)-4,5-dihy-
droimidazol-1-yl)methyl)pyridine hydrochloric acid salt 13b: yield,
1
91%; mp 205.6-206.4 °C; H NMR (400 Mz, DMSO-d6) δ 11.55 (s,
1H), 8.63 (s, 1H), 8.28 (d, J ) 2.4 Hz, 1H), 7.70 (dd, J1 ) 2.4 Hz, J2
) 8.0 Hz, 1H), 7.77 (d, J ) 3.6 Hz, 1H), 7.50 (d, J ) 8.0 Hz, 1H),
6.28 (dd, J1 ) 0.8 Hz, J2 ) 3.6 Hz, 1H), 4.78 (d, J ) 15.2 Hz, 1H),
4.68 (d, J ) 15.2 Hz, 1H), 4.11-4.13 (m, 4H), 2.37 (s, 3H); 13C NMR
(100 Mz, DMSO-d6) δ 164.2, 159.0, 150.7, 150.3, 143.7, 140.4, 132.3,
130.4, 129.5, 124.7, 124.5, 113.2, 49.7, 46.8, 44.6, 14.4; HRMS (EI+)
calcd for C16H15N4O335Cl (M+), 346.0833; found, 346.0834; calcd for
C16H15N4O337Cl (M+), 348.0803; found, 348.0812.
Scheme 2. Reaction of Nitromethylene Compound 6-Cl-PMNI with R,ꢀ-
Unsaturated Aldehydes and Five-Membered Aromatic Aldehydes
(Z)-2-Chloro-5-((2-(2-(5-ethylfuran-2-yl)-1-nitroVinyl)-4,5-dihydroim-
idazol-1-yl)methyl)pyridine hydrochloric acid salt 13c: yield, 62%; mp
167.7-168.2 °C; 1H NMR (400 Mz, DMSO-d6): δ 11.50 (s, 1H), 8.65
(s, 1H), 8.25 (d, J ) 2.0 Hz, 1H), 7.67-7.70 (m, 2H), 7.49 (dd, J1 )
0.4 Hz, J2 ) 8.0 Hz, 1H), 6.65 (d, J ) 3.6 Hz, 1H), 4.76 (d, J ) 15.2
Hz, 1H), 4.70 (d, J ) 15.2 Hz, 1H), 4.04-4.19 (m, 4H), 2.60-2.76
(m, 2H), 1.13 (t, J ) 15.2, 3H); 13C NMR (100 Mz, DMSO-d6) δ 169.0,
159.0, 150.7, 150.4, 143.6, 140.4, 132.3, 130.6, 129.4, 124.7, 124.5,
111.8, 49.7, 46.8, 44.6, 21.8, 14.4; HRMS (EI+) calcd for
C17H17N4O335Cl (M+), 360.0989; found, 360.0989; calcd for
C17H17N4O337Cl (M+), 362.0960; found, 360.0974.
(Z)-2-Chloro-5-((2-(2-(4,5-dimethylfuran-2-yl)-1-nitroVinyl)-4,5-di-
hydroimidazol-1-yl)methyl)pyridine hydrochloric acid salt 13d: yield,
1
58%; mp 190.1-191.0 °C; H NMR (400 Mz, DMSO-d6) δ 11.52 (s,
1H), 8.57 (s, 1H), 8.27 (d, J ) 2.4 Hz, 1H), 7.69 (dd, J1 ) 2.4 Hz, J2
) 8.4 Hz, 1H), 7.54 (s, 1H), 7.49 (d, J ) 8.4 Hz, 1H), 4.75 (d, J )
15.2 Hz, 1H), 4.66 (d, J ) 15.2 Hz, 1H), 4.05-4.16 (m, 4H), 2.28 (s,
3H), 2.00 (s, 3H); 13C NMR (100 Mz, DMSO-d6) δ 160.8, 159.1, 150.6,
150.3, 142.5, 140.3, 130.1, 129.5, 124.7, 123.9, 122.0, 49.8, 46.8, 44.5,
12.6, 9.6; HRMS (EI+) calcd for C17H17N4O335Cl (M+), 360.0989;
found, 360.0990; calcd for C17H17N4O337Cl (M+), 362.0960; found,
360.0979.
five-membered aromatic aldehydes were used as the replacement
of R,ꢀ-unsaturated aldehydes, compounds 9 rather than 8 were
obtained (Scheme 2). Enlightened by all of the descriptions
above, we herein designed and synthesized a series of novel
neonicotinoid analogues (6) bearing nitroconjugated double bond
and five-membered heterocycles.
(Z)-(5-(2-(1-((6-Chloropyridin-3-yl)methyl)-4,5-dihydro-1H-imidazol-
2-yl)-2-nitroVinyl)furan-2-yl)methanol hydrochloric acid salt 13e: yield,
1
MATERIALS AND METHODS
72%; mp 172.0-172.5 °C; H NMR (400 Mz, DMSO-d6) δ 11.42 (s,
1H), 8.69 (s, 1H), 8.29 (d, J ) 2.4 Hz, 1H), 7.72 (dd, J1 ) 2.4 Hz, J2
) 8.0 Hz, 1H), 7.67 (d, J ) 3.6 Hz, 1H), 7.51 (d, J ) 8.0 Hz, 1H),
6.76 (d, J ) 3.6 Hz, 1H), 4.80 (d, J ) 15.2 Hz, 1H), 4.66 (d, J ) 15.2
Hz, 1H), 4.52 (d, J ) 2.8 Hz, 2H), 4.14-4.19 (m, 2H), 4.04-4.10 (m,
2H); 13C NMR (100 Mz, DMSO-d6) δ 166.5, 158.9, 150.7, 150.3, 144.1,
140.3, 131.2, 130.8, 129.5, 125.3, 124.7, 112.5, 56.4, 49.7, 46.9, 44.5;
HRMS (ES+) calcd for C16H16N4O435Cl (M + H)+, 363.0815; found,
363.0830; calcd for C16H16N4O437Cl (M + H)+, 365.0831; found,
365.0829.
Instruments. Melting points (mp) were recorded on a Bu¨chi B540
apparatus (Bu¨chi Labortechnik AG, Flawil, Switzerland) and are
uncorrected. 1H NMR, 13C NMR, and 2D NMR (HMBC and HMQC)
spectra were recorded on a Bruker WP-500SY (500 MHz) or a Bruker
AM-400 (400 MHz) spectrometer with DMSO-d6 as the solvent and
TMS as the internal standard. Chemical shifts are reported in δ (parts
per million) values. High-resolution mass spectra were recorded under
electron impact (70 eV) condition using a MicroMass GCT CA 055
instrument. Combustion analyses for elemental composition were made
with an Elementar vario EL III. Analytical thin-layer chromatography
(TLC) was carried out on precoated plates (silica gel 60 F254), and
spots were visualized with ultraviolet (UV) light.
(Z)-2-Chloro-5-((2-(2-(5-chlorofuran-2-yl)-1-nitroVinyl)-4,5-dihy-
droimidazol-1-yl)methyl)pyridine hydrochloric acid salt 13f: yield, 77%;
1
mp 189.3-190.4 °C; H NMR (400 Mz, DMSO-d6) δ 12.05 (s, 1H),
8.72 (s, 1H), 8.27 (d, J ) 2.4 Hz, 1H), 7.76 (d, J ) 4.0 Hz, 1H), 7.72
(dd, J1 ) 2.4 Hz, J2 ) 8.0 Hz, 1H), 7.50 (d, J ) 8.0 Hz, 1H), 7.01 (d,
J ) 3.6 Hz, 1H), 4.79 (d, J ) 15.2 Hz, 1H), 4.74 (d, J ) 15.2 Hz,
1H), 4.13-4.23 (m, 2H), 3.99-4.09 (m, 2H); 13C NMR (100 Mz,
DMSO-d6) δ 158.3, 150.8, 150.3, 145.2, 144.6, 140.4, 131.4, 130.2,
129.3, 126.6, 124.7, 113.2, 49.9, 46.8, 44.8; HRMS (EI+) calcd for
C15H12N4O335Cl2 (M+), 366.0286; found, 366.0286; calcd for
C15H12N4O337Cl2 (M+), 370.0227; found, 370.0227.
Synthetic Procedures. Unless otherwise noted, reagents and solvents
were used as received from commercial suppliers. Yields were not
optimized.
General Synthetic Procedure for 13a-n, 14a-e, and 18a-c.
Concentrated hydrochloric acid (0.15 mL) was added to a stirred
mixture of compound 2 (12 or 17a–c) (4 mmol), five-membered
aromatic aldehyde (6 mmol), and acetonitrile (20 mL). The reaction
was carried out at room temperature, and the progress of the reaction
was monitored by TLC. After completion, the product was precipitated.
The precipitate was filtered, washed with dichloromethane, and dried
to give the corresponding product.
(Z)-2-Chloro-5-((2-(2-(5-bromofuran-2-yl)-1-nitroVinyl)-4,5-dihy-
droimidazol-1-yl)methyl)pyridine hydrochloric acid salt 13g: yield 79%;
1
mp 205.6-207.5 °C; H NMR (400 Mz, DMSO-d6) δ 11.15 (s, 1H),
(Z)-2-Chloro-5-((2-(2-(furan-2-yl)-1-nitroVinyl)-4,5-dihydroimidazol-
1-yl)methyl)pyridine hydrochloric acid salt 13a: yield, 93%; mp
200.4-201.6 °C; 1H NMR (400 Mz, DMSO-d6) δ 11.74 (s, 1H), 8.74
(s, 1H), 8.23 (d, J ) 2.4 Hz, 1H), 8.20 (d, J ) 1.2 Hz, 1H), 7.68-7.71
(m, 2H), 7.49 (d, J ) 8.4 Hz, 1H), 6.92 (dd, J1 ) 1.6 Hz, J2 ) 3.6 Hz,
8.74 (s, 1H), 8.28 (d, J ) 2.4 Hz, 1H), 7.77 (d, J ) 4.0 Hz, 1H), 7.72
(dd, J1 ) 2.4 Hz, J2 ) 8.0 Hz, 1H), 7.51 (d, J ) 8.0 Hz, 1H), 7.02 (d,
J ) 3.6 Hz, 1H), 4.81 (d, J ) 15.2 Hz, 1H), 4.75 (d, J ) 15.2 Hz,
1H), 4.14-4.23 (m, 2H), 4.00-4.10 (m, 2H); 13C NMR (100 Mz,
DMSO-d6) δ 158.4, 150.8, 150.3, 145.3, 144.5, 140.4, 131.6, 130.2,

Insecticidal Activities of Neonicotinoids
J. Agric. Food Chem., Vol. 57, No. 3, 2009 953
129.2, 126.5, 124.7, 113.2, 50.0, 46.9, 44.9; HRMS (ES+) calcd for
C15H13N4O335Cl79Br (M + H)+, 410.9860; found, 410.9855; calcd for
C15H13N4O335Cl81Br (M + H)+, 412.9839; found, 412.9849; calcd
for C15H13N4O337Cl79Br (M + H)+, 412.9830; found, 412.9849; calcd
for C15H13N4O337Cl81Br (M + H)+, 414.9810; found, 414.9800.
(Z)-2-Chloro-5-((2-(1-nitro-2-(5-nitrofuran-2-yl)Vinyl)-4,5-dihydroim-
idazol-1-yl)methyl)pyridine hydrochloric acid salt 13h: yield, 90%; mp
162.5-162.9 °C; 1H NMR (400 Mz, DMSO-d6) δ 11.80 (s, 1H), 8.92
(s, 1H), 8.29 (d, J ) 2.4 Hz, 1H), 7.89 (d, J ) 4.0 Hz, 1H), 7.83 (d,
J ) 4.0 Hz, 1H), 7.74 (dd, J1 ) 2.4 Hz, J2 ) 8.4 Hz, 1H), 7.51 (d, J
) 8.4 Hz, 1H), 4.89 (d, J ) 15.2 Hz, 1H), 4.71 (d, J ) 15.2 Hz, 1H),
4.10-4.19 (m, 4H); 13C NMR (100 Mz, DMSO-d6) δ 157.6, 150.4,
145.4, 144.6, 140.5, 131.5, 131.1, 130.1, 129.2, 128.6, 124.8, 114.3,
50.2, 46.9, 45.2; HRMS (EI+) calcd for C15H12N5O535Cl (M+),
377.0527; found, 377.0518; calcd for C15H12N5O537Cl (M+) (M+),
379.0497; found, 379.0524.
140.6, 139.4, 130.9, 130.1, 129.1, 128.7, 127.3, 124.7 49.7, 46.9, 44.7;
HRMS (EI+) calcd for C15H13N4O2S35Cl (M+), 348.0448; found,
348.0444.
(Z)-2-Chloro-5-((2-(1-nitro-2-(1H-pyrrol-2-yl)Vinyl)-4,5-dihydroimi-
dazol-1-yl)methyl)pyridine hydrochloric acid salt 13n: yield, 51%; mp
239.0-240.1 °C; 1H NMR (400 Mz, DMSO-d6) δ 12.96 (s, 1H), 11.49
(br, s, 1H), 8.25 (d, J ) 2.0 Hz, 1H), 7.68-7.71 (m, 2H), 7.50 (d, J )
8.4 Hz, 1H), 6.87 (s, 1H), 6.54 (t, J ) 2.0 Hz, 1H), 4.70 (d, J ) 15.2
Hz, 1H), 4.62 (d, J ) 15.2 Hz, 1H), 4.01-4.23 (m, 4H); 13C NMR
(100 Mz, DMSO-d6) δ 159.2, 150.7, 150.5, 140.6, 134.4, 132.9, 129.3,
124.7, 122.8, 121.2, 116.0, 49.4, 46.9, 44.4; HRMS (EI+) calcd for
C15H14N5O235Cl (M+), 331.0836; found, 331.0825; calcd for
C15H14N5O237Cl (M+), 333.0807; found, 333.0815.
(Z)-1-((6-chloropyridin-3-yl)methyl)-2-(2-(furan-2-yl)-1-nitroVinyl)-
1,4,5,6-tetrahydropyrimidine hydrochloric acid salt 14a: yield, 24%;
1
mp 126.3-127.2 °C; H NMR (400 Mz, DMSO-d6) δ 11.31 (s,1H),
(Z)-2-Chloro-5-((2-(2-(furan-3-yl)-1-nitroVinyl)-4,5-dihydroimidazol-
1-yl)methyl)pyridine hydrochloric acid salt 13i: yield, 69%; mp
175.3-175.9 °C; 1H NMR (400 Mz, DMSO-d6) δ 11.86 (s, 1H), 8.86
(s, 1H), 8.70 (s, 1H), 8.27 (d, J ) 2.4 Hz, 1H), 8.02 (s, 1H), 7.71 (dd,
J1 ) 2.4 Hz, J2 ) 8.4 Hz, 1H), 7.52 (d, J ) 8.4 Hz, 1H), 6.61 (d, J )
0.8 Hz, 1H), 4.75 (d, J ) 15.2 Hz, 1H), 4.68 (d, J ) 15.2 Hz, 1H),
4.05-4.25 (m, 4H); 13C NMR (100 Mz, DMSO-d6) δ 157.9, 154.9,
150.8, 150.6, 148.2, 140.7, 137.8, 129.2, 128.9, 124.8, 116.8, 108.7,
49.7, 46.9, 44.6; HRMS (EI+) calcd for C15H13N4O335Cl (M+),
332.0676; found, 332.0676; calcd for C15H13N4O337Cl (M+), 334.0674;
found, 334.0651.
8.61 (s, 1H), 8.22-8.23 (m, 2H), 7.64-7.68 (m, 2H), 7.47 (d, J ) 8.2
Hz, 1H), 6.90 (dd, J1 ) 1.6 Hz, J2 ) 3.6 Hz, 1H), 4.84 (d, J ) 15.6
Hz, 1H), 4.68 (d, J ) 15.6 Hz, 1H), 3.62-3.74 (m, 2H), 3.54 (s, 2H),
2.06-2.16 (m, 2H); 13C NMR (100 Mz, DMSO-d6) δ 153.6, 152.9,
150.5, 150.1, 145.2, 140.0, 131.6, 129.8, 129.4, 129.0, 124.6, 115.4,
55.2, 52.8, 46.5, 18.1; HRMS (EI+) calcd for C16H15N4O335Cl (M+),
346.0833; found, 346.0831; calcd for C16H15N4O337Cl (M+), 348.0803;
found, 348.0818.
(Z)-1-((6-Chloropyridin-3-yl)methyl)-2-(2-(5-methylfuran-2-yl)-1-ni-
troVinyl)-1,4,5,6-tetrahydropyrimidine hydrochloric acid salt 14b: yield,
1
75%; mp 213.7-213.9 °C; H NMR (400 Mz, DMSO-d6) δ 11.31 (s,
(Z)-2-Chloro-5-((2-(1-nitro-2-(thiophen-2-yl)Vinyl)-4,5-dihydroimi-
dazol-1-yl)methyl)pyridine hydrochloric acid salt 13j: yield, 90%; mp
188.8-189.7 °C; 1H NMR (400 Mz, DMSO-d6) δ 12.11 (s, 1H), 9.18
(s, 1H), 8.37 (d, J ) 4.8 Hz, 1H), 8.27 (d, J ) 1.6 Hz, 1H), 8.14 (d,
J ) 3.6 Hz, 1H), 7.71 (dd, J1 ) 2.0 Hz, J2 ) 8.4 Hz, 1H), 7.50 (d, J
) 8.4 Hz, 1H), 7.43 (t, J ) 4.4 Hz, 1H), 4.82 (d, J ) 15.2 Hz, 1H),
4.68 (d, J ) 15.2 Hz, 1H), 4.15 (s, 4H); 13C NMR (100 Mz, DMSO-
d6) δ 157.8, 150.8, 150.6, 143.2, 140.6, 140.4, 139.3, 131.4, 130.6,
129.1, 127.2, 124.7 49.7, 46.9, 44.8; HRMS (EI+) calcd for
C15H13N4O2S35Cl (M+), 348.0448; found, 348.0446; calcd for
C15H13N4O2S37Cl (M+), 350.0418; found, 350.0431. Anal. Calcd for
C15H14N4O2SCl2: C, 46.76; H, 3.66; N, 14.54. Found: C, 46.80; H, 3.42;
N, 14.72.
1H), 8.48 (s, 1H), 8.25 (d, J ) 2.4 Hz, 1H), 7.68 (dd, J1 ) 2.4 Hz, J2
) 8.4 Hz, 1H), 7.59 (d, J ) 3.6 Hz, 1H), 7.47 (d, J ) 8.4 Hz, 1H),
6.60 (d, J ) 3.6 Hz, 1H), 4.84 (d, J ) 15.2 Hz, 1H), 4.69 (d, J ) 15.2
Hz, 1H), 3.64-3.77 (m, 2H), 3.52 (s, 2H), 2.41 (s, 3H), 2.04-2.09
(m, 2H); 13C NMR (100 Mz, DMSO-d6) δ 163.8, 153.8, 150.5, 150.2,
144.2, 140.1, 131.6, 130.1, 129.9, 128.9, 124.6, 112.9, 52.8, 46.8, 18.3,
14.2; HRMS (EI+) calcd for C17H17N4O335Cl (M+), 360.0989; found,
360.0989; calcd for C17H17N4O337Cl (M+), 362.0960; found, 362.0969.
(Z)-1-((6-Chloropyridin-3-yl)methyl)-2-(2-(5-chlorofuran-2-yl)-1-ni-
troVinyl)-1,4,5,6-tetrahydropyrimidine hydrochloric acid salt 14c: yield,
1
43%; mp 235.5-236.1 °C; H NMR (400 Mz, DMSO-d6) δ 10.88 (s,
1H), 8.59 (s, 1H), 8.26 (d, J ) 2.4 Hz, 1H), 7.69-7.72 (m, 2H), 7.48
(d, J ) 8.4 Hz, 1H), 6.99 (d, J ) 4.0 Hz, 1H), 4.89 (d, J ) 15.6 Hz,
1H), 4.73 (d, J ) 15.6 Hz, 1H), 3.72-3.74 (m, 2H), 3.53-3.54 (m,
2H), 2.04-2.18 (m, 2H); 13C NMR (100 Mz, DMSO-d6) δ 153.4, 150.7,
150.2, 145.1, 144.8, 140.1, 131.9, 130.9, 129.7, 128.4, 124.6, 113.1,
52.9, 47.0, 18.0; HRMS (ES+) calcd for C16H14N4O335Cl2 (M + H)+,
381.0521; found, 381.0503; calcd for C16H14N4O335Cl37Cl (M + H)+,
383.0492; found, 383.0480; calcd for C16H14N4O337Cl2 (M + H)+,
385.0462; found, 385.0479.
(Z)-5-((2-(2-(4-Bromothiophen-2-yl)-1-nitroVinyl)-4,5-dihydroimida-
zol-1-yl)methyl)-2-chloropyridine hydrochloric acid salt 13k: yield,
1
88%; mp 161.0-162.0 °C; H NMR (400 Mz, DMSO-d6) δ 12.19 (s,
1H), 9.13 (s, 1H), 8.46 (s, 1H), 8.29 (d, J ) 2.4 Hz, 1H), 8.12 (d, J )
1.2 Hz, 1H), 7.72 (dd, J1 ) 2.4 Hz, J2 ) 8.4 Hz, 1H), 7.51 (d, J ) 8.4
Hz, 1H), 4.83 (d, J ) 15.2 Hz, 1H), 4.69 (d, J ) 15.2 Hz, 1H), 4.15
(s, 4H); 13C NMR (100 Mz, DMSO-d6) δ 155.6, 149.2, 148.9, 141.8,
139.0, 136.3, 134.8, 130.9, 127.4, 126.8, 123.1, 110.8, 48.2, 45.3,
43.2; HRMS (ES+) calcd for C15H13N4O2S79Br35Cl (M + H+),
426.9631; found, 426.9640; calcd for C15H13N4O2S81Br35Cl (M +
H+), 428.9611; found, 428.9631; calcd for C15H13N4O2S79Br37Cl (M
+ H+), 428.9602; found, 428.9631; calcd for C15H13N4O2S81Br37Cl
(M + H+), 430.9581; found, 430.9594.
(Z)-1-((6-Chloropyridin-3-yl)methyl)-2-(1-nitro-2-(thiophen-2-yl)Vi-
nyl)-1,4,5,6-tetrahydropyrimidine hydrochloric acid salt 14d: yield,
1
69%; mp 160.5-161.3 °C; H NMR (400 Mz, DMSO-d6) δ 11.74 (s,
1H), 9.06 (s, 1H), 8.33 (dt, J1 ) 1.2 Hz, J2 ) 5.2 Hz, 1H), 8.24 (d, J
) 2.4 Hz, 1H), 8.10 (dd, J1 ) 0.8 Hz, J2 ) 3.6 Hz, 1H), 7.68 (dd, J1
) 2.4 Hz, J2 ) 8.2 Hz, 1H), 7.48 (dd, J1 ) 0.4 Hz, J2 ) 8.2 Hz, 1H),
7.42 (dd, J1 ) 4.0 Hz, J2 ) 5.0 Hz, 1H), 4.88 (d, J ) 15.2 Hz, 1H),
4.70 (d, J ) 15.2 Hz, 1H), 3.71 (t, J ) 5.6, 2H), 3.55-3.62 (m, 2H),
2.06-2.26 (m, 2H); 13C NMR (100 Mz, DMSO-d6) δ 152.7, 150.7,
150.5, 143.0, 140.4, 140.0, 137.6, 132.4, 131.7, 130.4, 129.4, 124.6,
52.9, 46.6, 17.9; HRMS (EI+) calcd for C16H15N4O2S35Cl (M+),
362.0605; found, 362.0604; calcd for C16H15N4O2S37Cl (M+), 364.0575;
found, 364.0580.
(Z)-2-Chloro-5-((2-(2-(5-methylthiophen-2-yl)-1-nitroVinyl)-4,5-di-
hydroimidazol-1-yl)methyl)pyridine hydrochloric acid salt 13l: yield,
64%; mp 170.7-171.3 °C; 1H NMR (400 Mz, DMSO-d6) δ 9.10 (d, J
) 1.2 Hz, 1H), 8.29 (d, J ) 2.4 Hz, 1H), 8.01 (d, J ) 3.6 Hz, 1H),
7.72 (d, J ) 8.0 Hz, 1H), 7.51 (d, J ) 8.0 Hz, 1H), 7.19 (d, J ) 4.0
Hz, 1H), 4.82 (d, J ) 15.2 Hz, 1H), 4.67 (d, J ) 15.2 Hz, 1H),
4.11-4.17 (m, 4H), 2.60 (s, 3H); 13C NMR (100 Mz, DMSO-d6) δ
157.9, 156.6, 150.8, 150.6, 144.7, 140.6, 139.4, 129.7, 129.6, 129.2,
125.6, 124.7, 49.6, 46.9, 44.6, 16.6; HRMS (EI+) calcd for
C16H15N4O2S35Cl (M+), 362.0604; found, 362.0604; calcd for
C16H15N4O2S37Cl (M+), 364.0575; found, 364.0564.
(Z)-1-((6-Chloropyridin-3-yl)methyl)-2-(2-(5-methylthiophen-2-yl)-
1-nitroVinyl)-1,4,5,6-tetrahydropyrimidine hydrochloric acid salt 14e:
yield, 15%; mp 208.6-209.4 °C; 1H NMR (400 Mz, DMSO-d6) δ 11.57
(s, 1H), 8.96 (s, 1H), 8.27 (d, J ) 1.6 Hz, 1H), 7.98 (d, J ) 3.6 Hz,
1H), 7.70 (dd, J1 ) 2.0 Hz, J2 ) 8.4 Hz, 1H), 7.50 (d, J ) 8.4 Hz,
1H), 7.19 (d, J ) 3.6 Hz, 1H), 4.88 (d, J ) 15.6 Hz, 1H), 4.69 (d, J
) 15.6 Hz, 1H), 3.66-3.77 (m, 2H), 3.55-3.63 (m, 2H), 2.61 (s, 3H),
2.21-2.26 (m, 1H), 2.05-2.10 (m, 1H); 13C NMR (100 Mz, DMSO-
d6) δ 156.1, 152.9, 150.7, 150.4, 144.3, 140.4, 137.7, 131.2, 129.8,
129.5, 129.5, 124.6, 52.8, 46.6, 18.0, 16.6; HRMS (EI+) calcd for
(Z)-2-Chloro-5-((2-(1-nitro-2-(thiophen-3-yl)Vinyl)-4,5-dihydroimi-
dazol-1-yl)methyl)pyridine hydrochloric acid salt 13m: yield, 35%; mp
1
95.8-96.1 °C; H NMR (400 Mz, DMSO-d6) δ 8.89 (s, 1H), 8.62 (s,
1H), 8.23 (s, 1H), 7.80 (s, 1H), 7.66 (d, J ) 7.2 Hz, 1H), 7.42 (d, J )
8.4 Hz, 1H), 7.27 (d, J ) 4.8 Hz, 1H), 4.66-4.77 (m, 2H), 4.08-4.24
(m, 4 H); 13C NMR (100 Mz, DMSO-d6) δ 158.3, 150.7, 150.5, 141.4,

954 J. Agric. Food Chem., Vol. 57, No. 3, 2009
Shao et al.
Scheme 3a
a Reagents and conditions: (a) ethane-1,2-diamine or propane-1,3-diamine, CH3CN, 0-5 °C; (b) 1,1-bis(methylthio)-2-nitroethene, CH3CH2OH, refluxing; (c)
CH3CN, various aldehyde, concentrated HCl, rt.
C17H17N4O2S35Cl (M+), 376.0761; found, 376.0762; calcd for
C17H17N4O2S37Cl (M+), 378.0731; found, 378.0728.
the burgeons were placed in the conditioned room (25 ( 1 °C, 50%
RH). Water containing Triton X-100 (0.1 mg L-1) was used as 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.
Insecticidal Test for Armyworm (Pseudaletia separate Walker). The
activities of insecticidal compounds against armyworm were tested
using previously reported procedures (26, 27). 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
dishes. The leaves were then sprayed with the compound solution and
exposed to dry. The dishes were infested with 10 second-instar larvae
and placed in the conditioned room. The mortality rates were evaluated
48 h after treatment. Each treatment had three repetitions, and the data
were adjusted and subjected to probit analysis as before.
(Z)-1-Benzyl-2-(2-(furan-2-yl)-1-nitroVinyl)-4,5-dihydro-1H-imida-
1
zole hydrochloric acid salt 18a: yield, 56%; mp 185.7-187.8 °C; H
NMR (400 Mz, DMSO-d6) δ 8.74 (s, 1H), 8.25 (s, 1H), 7.72 (d, J )
3.2 Hz, 1H), 7.31-7.32 (m, 3H), 7.17-7.19 (m, 2H), 6.93 (d, J ) 1.6
Hz, 1H), 4.67 (d, J ) 15.2 Hz, 1H), 4.56 (d, J ) 15.2 Hz, 1H),
4.00-4.15 (m, 4H); 13C NMR (100 Mz, DMSO-d6) δ 158.4, 153.2,
145.0, 133.8, 131.0, 129.6, 129.2, 128.8, 128.7, 126.4, 115.6, 50.3,
49.5, 44.4; HRMS (EI+) calcd for C16H15N3O3 (M+), 297.1113; found,
297.1113.
(Z)-1-(4-Chlorobenzyl)-2-(2-(furan-2-yl)-1-nitroVinyl)-4,5-dihydro-
1H-imidazole hydrochloric acid salt 18b: yield, 51%; mp 194.8-195.1
1
°C; H NMR (400 Mz, DMSO-d6) δ 8.74 (s, 1H), 8.22 (s, 1H), 7.76
(d, J ) 3.2 Hz, 1H), 7.39 (d, J ) 8.4 Hz, 2H), 7.22 (d, J ) 8.4 Hz,
2H), 6.93 (dd, J1 ) 1.6 Hz, J2 ) 3.2 Hz, 1H), 4.71 (d, J ) 15.2 Hz,
1H), 4.57 (d, J ) 15.2 Hz, 1H), 4.01-4.15 (m, 4H); 13C NMR (100
Mz, DMSO-d6) δ 158.6, 153.2, 145.0, 133.5, 132.9, 131.2, 130.7, 129.7,
129.2, 126.3, 115.6, 49.5, 44.4; HRMS (EI+) calcd for C16H14N3O335Cl
(M+), 331.0724; found, 331.0724; calcd for C16H14N3O337Cl (M+),
333.0694; found, 333.0716.
Insecticidal Test for Small Brown Rice Planthopper (Laodelphasx
striatellus) and Nephotettix bipunctatus (Fabricius). The activities of
insecticidal compounds against brown rice planthopper and N. bipunc-
tatus (Fabricius) were tested using the dipping method previously
reported (28). Rice plants (Shanyou 63) at tillering to booting stage
were pulled out, and the rice stems (about 10 cm lengths) with roots
were cut and air-dried to remove excess water. Three rice stems were
dipped in appropriate solutions of the tested compound for 30 s. After
the rice stems had been air-dried, the rice roots was wrapped in
moistened cotton. Then the rice stems were placed into a tumbler. Thirty
L. striatellus or N. bipunctatus were introduced into the tumbler, and
the treated insects were maintained at a temperature of 27 ( 1 °C. The
distilled water only was used as control for each chemical. Each process
was repeated three times, and the mortality rates were evaluated 48 h
after treatment. The data were adjusted and subjected to probit analysis
as before.
(Z)-1-((2-Chlorothiazol-5-yl)methyl)-2-(2-(furan-2-yl)-1-nitroVinyl)-
4,5-dihydro-1H-imidazole hydrochloric acid salt 18c: yield, 63%; mp
1
198.2-198.7 °C; H NMR (400 Mz, DMSO-d6) δ 8.75 (s, 1H), 8.19
(s, 1H), 7.71 (d, J ) 3.2 Hz, 1H), 7.61 (s, 1H), 6.92-6.93 (m, 1H),
4.97 (s, 2H), 4.13 (s, 4 H); 13C NMR (100 Mz, DMSO-d6) δ 158.4,
153.2, 152.2, 145.0, 142.9, 133.6, 131.2, 129.7, 126.0, 115.7, 49.3,
44.6, 42.3; HRMS (EI+) calcd for C13H11N4O3S35Cl (M+), 338.0240;
found, 338.0240; calcd for C13H11N4O3S37Cl (M+), 340.0211; found,
340.0213.
Biological Assay. All bioassays were performed on representative
test organisms reared in the laboratory. The bioassay was repeated at
25 ( 1 °C according to statistical requirements. All compounds were
dissolved in N,N-dimethylformamide (AP, Shanghai Chemical Reagent
Co., Ltd., Shanghai, China) and diluted with distilled water containing
Triton X-100 (0.1 mg L-1) to obtain series concentrations of 500.0,
250.0, and 125.0 mg L-1 and others for bioassays. For comparative
purposes, imidacloprid was tested under the same conditions.
Insecticidal Test for Cowpea Aphids (Aphis cracciVora). The
activities of insecticidal compounds against cowpea aphids were tested
byleaf-dipmethodaccordingtoourpreviouslyreportedprocedure(15,25).
Horsebean plant leaves 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 dilution was sucked out with filter paper;
RESULTS AND DISCUSSION
Synthesis. The synthetic procedures for the title compounds
are depicted in Schemes 3 and 4. Starting from 10 and 15a-c,
a set of diamines 11a-b and 16a-c, nitromethylene 2, 12, and
17a-c were prepared following the procedure reported previ-
ously (29). Then compounds 2, 12, and 17a-c could readily
react with various five-membered aromatic aldehydes catalyzed
by concentrated hydrochloric acid to give the title compounds
13a-n, 14a-e, and 18a-c at room temperature. The amount
of hydrochloric acid should be strictly controlled to allow the

Insecticidal Activities of Neonicotinoids
J. Agric. Food Chem., Vol. 57, No. 3, 2009 955
Scheme 4a
Table 1. NMR Data and HMBC and NOESY Correlations of Compound
13a
atom no.
δH (m, J in Hz)
δC
HMBC (δH to δC)
NOESY
6
1
2
3
4
5
6
150.7
124.7
140.3
129.5
150.3
46.9
7.49 (d, 8.4)
7.68-7.71(m)
1, 3, 4
1, 2, 6
a Reagents and conditions: (a) ethane-1,2-diamine, CH3CN, 0-5 °C; (b)
1,1-bis(methylthio)-2-nitroethene, CH3CH2OH, refluxing; (c) CH3CN, furan-2-
carbaldehyde, concentrated HCl, rt.
8.23 (d, 2.4)
1, 2, 3, 4, 6
3, 4, 5, 7, 9
6, 7
5, 7
4.78 (d, 15.6)
4.67 (d, 15.6)
4.08-4.18 (m)
4.08-4.18 (m)
7
8
9
10
11
12
13
14
15
49.7
44.5
8, 9
7, 9
5, 6
product to precipitate from the reaction mixture. When the
reaction took place at high temperature (>60 °C), a large amount
of tar was produced and the yield was rather low (<10%).
Unexpectedly, six-membered aromatic aldehydes, such as
2-pyridinaldehyde, 3-pyridinaldehyde, benzaldehyde, 4-meth-
oxybenzaldehyde, and 4-nitrobenzaldehyde, could not react with
intermediate 2 to provide the corresponding compounds, which
might be due to the low electrophilic reactivities of these
compounds. Attempts to synthesize the corresponding products
by using aliphatic aldehydes (trifluoroacetaldehyde, butyralde-
hyde, and cyclohexanecarbaldehyde) were also unsuccessful
even if the reaction mixture was heated to reflux.
158.7
126.2
131.1
144.9
129.7
115.6
153.2
8.74 (s)
9, 10, 12, 13
13
7.68-7.71(m)
6.92 (dd, 1.6, 3.6)
8.20 (d, 1.2)
11, 12, 14,15
12, 13, 15
12, 13, 14
11, 14
13, 15
14
Table 2. Insecticidal Activities of Compounds 13a-n, 14a-e, and 18a-c
and Imidacloprid against Cowpea Aphids (Aphis craccivora) and Armyworm
(Pseudaletia separate Walker)
The structures of all synthesized compounds were confirmed
by NMR and HRMS. A broad peak at δ 11-12.5 in the H
A. craccivora
mortality
(%, 500 mg L-1) (mmol L-1) (%, 500 mg L-1) (mmol L-1
P. separate Walker
1
LC50
mortality LC50
compd n Heta
13a
NMR spectra of all the compounds and elemental analyses of
13a and 13j showed that the target compounds were obtained
as hydrochloric acid salts. Moreover, heteronuclear chemical
shift correlation experiments (HMBC, HMQC, and NOESY)
were performed to assign all of the signals of the 13C NMR
spectrum and to confirm the assignments made for the 1H NMR
spectrum. A complete assignment of the proton signals and
selected HMBC and NOESY correlations of compound 13a is
shown in Table 1.
)
0 H1
0 H2
0 H3
0 H4
0 H5
0 H6
0 H7
0 H8
0 H9
0 H10
0 H11
0 H12
0 H13
0 H14
1 H1
1 H2
1 H6
1 H10
1 H12
100
100
100
100
100
100
100
100
100
100
0
0.00372
0.00634
0.00182
0.00465
0.01058
0.00754
0.00730
0.01109
0.00446
0.00423
nt
100
100
100
0
100
100
100
100
100
100
0
0.02470
0.05313
0.09790
ntb
0.03387
0.03761
0.03973
0.06954
0.05530
0.05288
nt
13b
13c
13d
13e
13f
13g
13h
13i
13j
13k
13l
Bioassay. Insecticidal ActiVities against Cowpea Aphids
(Aphis cracciVora) and Armyworm (Pseudaletia separate Walker).
Table 2 shows the insecticidal activities of the title compounds
against cowpea aphids and armyworm. Most of the title
compounds showed excellent insecticidal activities against
cowpea aphids, and some of them were as active as or more so
than imidacloprid. For example, the LC50 values of compounds
13a, 13c, 13i, 13j, 13l, and 18c were 0.00372, 0.00182, 0.00446,
0.00423, 0.00311, and 0.00350 mmol L-1, respectively, whereas
that of imidacloprid was only 0.03502 mmol L-1. Against
armyworm, the title compounds also had high insecticidal
activities, whereas the activities of imidacloprid were weak,
which implied that introduction of the five-membered aromatic
heterocycles improved the insecticidal activities against not only
homoptera insects but also lepidoptera insects. Unexpectedly,
compound 13d demonstrated high insecticidal activity against
cowpea aphids but was inactive against armyworm, whereas
13k and 13m had very low or no activity. The insecticidal
activities of the six-membered ring analogues 14a-e were
lower than those of the corresponding five-membered ring
compounds. Replacement of 2-chloro-5-pyridine in 13a with
2-chloro-5-thiazole to generate analogue 18c maintained high
insecticidal activities because the 2-chloro-5-thiazole unit has
been shown to be an effective bioisosteric replacement for
the 2-chloro-5-pyridine, whereas benzyl analogue 18a and
100
31.9
0.00311
nt
100
0
0.02965
nt
13m
13n
14a
14b
14c
14d
14e
18a
18b
18c
imidacloprid
100
100
100
100
100
100
0
98.0
100
100
0.01117
0.07642
0.6975
0.06091
0.02050
0.02464
nt
0.23440
0.00350
0.03502
100
16.7
0.03967
nt
nt
nt
nt
nt
nt
nt
33.3
96.7
73.3
63.3
46.6
67.2
100
nt
0.10727
nt
a Het, five-membered aromatic heterocycles. b nt, not tested.
4-chlorobenzyl analogue 18b showed low insecticidal activi-
ties as anticipated.
Insecticidal ActiVities against Nephotettix bipunctatus (Fab-
ricius). Considering the bioassay results described above,
compounds 13a, 13b, 13e, 13g, 13h, and 13j were selected to
further evaluate the activities against N. bipunctatus (Fabricius),
and the results are shown in Table 3. The results indicated that
all compounds except 13h possessed higher insecticidal activities
than imidacloprid against N. bipunctatus (Fabricius). Especially,
compounds 13a, 13e, and 13j exhibited 16.0-, 18.8-, and 17.1-
fold potency compared with imidacloprid, respectively.

956 J. Agric. Food Chem., Vol. 57, No. 3, 2009
Shao et al.
Table 3. Insecticidal Activities of Compounds 13a, 13b, 13e, 13g, 13h,
and 13j and Imidacloprid against Nephotettix bipunctatus (Fabricius)
(5) Kagabu, S.; Ishihara, R.; Nishimura, K.; Naruse, Y. Insecticidal
and neuroblocking potencies of variants of the imidazolidine
moiety of imidacloprid-related neonicotinoids and the relationship
to partition coefficient and charge density on the pharmacophore.
J. Agric. Food Chem. 2007, 55, 812–818.
(6) Mencke, N.; Jeschke, P. Therapy and preventions of parasitic
insects in veterinary medicine using imidacloprid. Curr. Top. Med.
Chem. 2002, 2, 701–715.
compd
13a
13b
y ) a + bx
LC50 (mmol L-1
)
toxic ratioa
y ) 5.5133 + 1.5925x
y ) 4.7336 + 1.4034x
y ) 5.5617 + 1.5613x
y ) 4.9021 + 1.7913x
y ) 2.9553 +1.1326x
y ) 5.4564 + 1.3838x
y ) 4.2828 + 0.9880x
0.00130
0.00405
0.00111
0.00254
0.15430
0.00122
0.02086
16.0
5.2
18.8
8.2
0.1
17.1
1
13e
13g
13h
13j
(7) Nauen, R.; Denholm, I. Resistance of insect pests to neonicotinoid
insecticides: current status and future prospects. Arch. Insect
Biochem. Physiol. 2005, 58, 200–215.
imidacloprid
(8) Nauen, R.; Elbert, A. Resistance of Bemisia tabaci (Homoptera:
Aleyrodidae) to insecticides in southern Spain with special
reference to neonicotinoids. Pest Manag. Sci. 2000, 56, 60–64.
(9) Reyes, M.; Franck, P.; Charmillot, P. J.; Ioriatti, C.; Olivares, J.;
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Liu, C. J. Selection for imidacloprid resistance in NilaparVata
lugens: cross-resistance patterns and possible mechanisims. Pest
Manag. Sci. 2003, 59, 1355–1359.
a Toxic ratio is defined as the ratio of imidacloprid’s LC50 value for baseline
toxicity and the compounds’ LC50 value.
Table 4. Insecticidal Activities of Compounds 13a and 13j and
Imidacloprid against Small Brown Rice Planthopper (Laodelphasx
striatellus)
compd
13a
13j
y ) a + bx
LC50 (mmol L-1
)
toxic ratioa
y ) 4.2260 + 1.8230x
y ) 3.8342 + 1.5961x
y ) 2.7972 + 1.9958x
0.00723
0.01397
0.04980
6.9
3.6
1
imidacloprid
(11) Ninsin, K. D. Acetamiprid resistance and cross-resistance in the
diamondback moth, Plutella xylostella. Pest Manag. Sci. 2004,
60, 839–841.
a Toxic ratio is defined as the ratio of imidacloprid’s LC50 value for baseline
toxicity and the compounds’ LC50 value.
(12) Sanchez, D. M.; Hollingworth, R. M.; Grafius, E. J.; Moyer, D. D.
Resistance and cross-resistance to neonicotinoid insecticides and
spinosad in the Colorado potato beetle, Leptinotarsa decemlineata
(Say) (Coleoptera: Chrysomelidae). Pest Manag. Sci. 2006, 62,
30–37.
(13) Gorman, K. G.; Devine, G.; Bennison, J.; Coussons, P.; Punchard,
N.; Denholm, I. Report of resistance to the neonicotinoid
insecticide imidacloprid in Trialeurodes Vaporariorum (Hemi-
ptera: Aleyrodidae). Pest Manag. Sci. 2007, 63, 555–558.
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of Musca domestica from Danish livestock farms. Pest Manag.
Sci. 2008, 64, 126–132.
(15) Tian, Z. Z.; Shao, X. S.; Li, Z.; Qian, X. H. Synthesis, insecticidal
activity, and QSAR of novel nitromethylene neonicotinoids with
tetrahydropyridine fixed cis configuration and exo-ring ether
modification. J. Agric. Food Chem. 2007, 55, 2288–2292.
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Yamamoto, I., Casida, J. E., Eds.; Springer-Verlag: Tokyo, Japan,
1999; pp 177-209.
(17) Shiokawa, K.; Tsuboi, S.; Kagabu, S.; Moriya, K. Nitromethylene
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Insecticidal ActiVities against Small Brown Rice Planthopper
(Laodelphasx striatellus). Table 4 shows the insecticidal activi-
ties of compounds 13a and 13j and imidacloprid against small
brown rice planthopper. The results show that the insecticidal
activities of compounds 13a and 13j against small brown rice
planthopper were 6.9- and 3.6-fold as high as that of imida-
cloprid on the basis of the LC50 value.
In conclusion, a series of a novel class of neonicotinoids,
in which the common nitromethylene pharmacophore was
replaced by a nitroconjugated system, were designed and
synthesized. Most of the compounds exhibited excellent
insecticidal activities against cowpea aphids (A. cracciVora),
armyworm (P. separate Walker), N. bipunctatus (Fabricius),
and small brown rice planthopper (L. striatellus), and some
of them showed higher activities than imidacloprid, which
implied that replacement of nitromethylene by the nitrocon-
jugated system was feasible to obtain novel neonicotinoids
analogues with high activities. In particular, derivatives 13a
and 13j, as two field-testing candidates, showed much higher
insecticidal activities than imidacloprid. Further field trial
and structural modifications of compounds 13a and 13j are
underway.
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Received for review October 22, 2008. Revised manuscript received
December 8, 2008. Accepted December 8, 2008. This work was
financially supported by the National Natural Science Foundation of
China (20502006, 2087203) and the National High Technology Research
and Development Program of China (863 Program, 2006AA10A201).
We appreciate partial support from the Shanghai Foundation of Science
and Technology (073919107, 064319022), Shanghai Leading Academic
Discipline Project, Project B507.
JF803305F