Insect Control: Biological and Synthetic Agents - Index of

70 3: Neonicotinoid Insecticides
3.3.2. Neonicotinoids Having Noncyclic
Structures
From the new chemical class of ring system containing
neonicotinoids noncyclic structures having the
same mode of action can also be deduced. These
noncyclic type neonicotinoids can have as separate
substituents [R 1 ,R 2 ] (i), e.g., for R 1 hydrogen or
alkyl like methyl (acetamiprid) and ethyl (nitenpyram)
and in the case of E ¼ NH for the substituent
R 2 alkyl like methyl (clothianidin and dinotefuran),
respectively.
3.3.2.1. N-[(6-chloro-3-pyridinyl)methyl]-N-ethyl-
N 0 -methyl-2-nitro-1,1,-ethenediamine (nitenpyram,
TI-304) Starting from the cyclic nithiazine
(Soloway et al., 1978), the acyclic nitenpyram (Bestguard
TM ) was discovered during optimization of
substituents of an acyclic nitroethene (Minamida
et al., 1993). The insecticidal activity of 1-(3-pyridylamino)-2-nitroethene
compounds against the
brown planthopper and the green leafhopper were
studied. It was found that the 1-methylamino-1-
(pyrid-3-ylmethylamino)-2-nitroethene was more
active than the corresponding 1-ethyl, 1-methoxy,
or 1-thiomethoxy derivatives. Introduction of
sterically large amino groups like ethylamino,
isopropylamino, hydrazino, N-pyrrolidino, or Nmorpholino
decreased the activity against the
green rice leafhopper. Furthermore, the methylene
bridge between the pyrid-3-yl and nitrogen was
replaced with other linkages. However, all attempts
at shortening and lengthening the linkage failed
to increase the insecticidal activities against the
brown planthopper and the green rice leafhopper
(Akayama and Minamida, 1999). Heterocyclic
aromatic substituents, different from pyrid-3-yl,
were incorporated into the nitroethen structure.
The replacement of pyrid-3-yl with 6-fluoro-pyrid-
3-yl, 6-chloro-pyrid-3-yl, 6-bromo-pyrid-3-yl, and
2-chloro-1,3-thiazol-5-yl enhanced the activity
against the brown planthopper.
3.3.2.2. (E)-N-[(6-chloro-3-pyridinyl)methyl]-
N 0 -cyano-N-methyl-ethanimidamide (acetamiprid,
NI-25) Acetamiprid (Takahashi et al., 1992;
Matsuda and Takahashi, 1996) has an N-cyanoamidine
structure, which contains in analogy to imidacloprid
and thiacloprid the CPM moiety. This
neonicotinoid was invented during a search for
nitromethylene derivatives by Nippon Soda Co.
Ltd. in 1989 and was registered in 1995 in Japan.
The insecticide is marketed under the trade name
Mospilan Õ for crop protection. The noncyclic acetamiprid
was discovered by optimization studies
of special 2-N-cyanoimino compounds with an
imidazolidine 5-ring obtained from Nihon Bayer
(Yamada et al., 1999). The noncyclic 2-nitromethylene
and 2-N-nitroimine derivatives are less active
than the corresponding ring structures, but numerous
noncyclic derivatives show excellent activities
against the armyworm and aphid as well as the
cockroach. Regarding the substituent on the amino
group, the N-methyl group exhibited the highest
activity against the diamondback moth, while
derivatives with hydrogen, N-methyl, and N-ethyl
showed potent activity against the cotton aphid
(Yamada et al., 1999).
3.3.2.3. [C(E)]-N-[(2-chloro-5-thiazolyl)methyl]-N 0 -
methyl-N 00 -nitroguanidine (clothianidin, TI-435) As
a result of continuous investigations of noncyclic
neonicotinoids, researchers from Nihon Bayer Agrochem
and Takeda in Japan found that these noncyclic
neonicotinoids showed high activities against
sucking insects. In the optimization process, Takeda
researchers were able to demonstrate that compounds
containing the nitroguanidine moiety, coupled
with the thiazol-5-ylmethyl residue, have
increased activity against some lepidopteran pests
(Uneme et al., 1999). This is in accordance with the
general pharmacophore [ w N w C(E)›X w Y], where ›
X w Y is an electron-withdrawing group such as ›
N w NO2, and E represents the NH w Me unit. After
further optimization in this subclass, clothianidin
(TI-435) emerged as the most promising derivative
from this program (Ohkawara et al., 2002; Jeschke
et al., 2003). Clothianidin has already been
registered in Japan for foliar and soil applications
under the trade names Dantotsu TM and Fullswing TM
(Sumitomo Chemical Takeda Agro), and also in
Korea, Taiwan, and other countries. Registrations
have also been granted in North America and
Europe for seed treatment under the brand name
Poncho Õ (Bayer CropScience).
In the novel noncyclic structure of clothianidin
(TI-435) (i.e., R ¼ H; E ¼ NHMe), the Nnitroguanidine
pharmacophore [ w N w C(N)›N w NO2]
is similar to that of imidacloprid, but the CPM group
has been replaced by the CTM moiety (Ohkawara
et al., 2002) (Figure 2). Clothianidin crystallizes
under normal laboratory conditions using common
solvents as needlelike crystals containing no additional
solvent or water molecules. The best-quality
crystals for X-ray structure analysis were obtained
by slow evaporation of a methanol/H2O (1 : 1) solution
at room temperature. Figure 8 shows a photograph
using polarized light of the crystal needle with
the dimensions 0.90 0.30 0.07 mm 3 used for
X-ray structure analysis (Jeschke et al., 2003). Clothianidin
(TI-435) was subjected to conformational