Insect Control: Biological and Synthetic Agents - Index of

64 3: Neonicotinoid Insecticides
Figure 4 Structural segments for neonicotinoids.
in the field to noninsecticidal compounds. In order
to avoid absorption of sunlight, a more stable functional
group was necessary. After preparation of
about 2000 compounds, imidacloprid (NTN33893)
containing a 2-(N-nitroimino) group (see Section
3.3.1.1), the first member of the second-generation
neonicotinoids, emerged from this project (Elbert
et al., 1990, 1991; Bai et al., 1991; Nauen et al.,
2001). The presence of an N-nitroimino group at
the 2-position of the imidazolidine ring makes little
difference to insecticidal activity compared with
compounds that contain a nitomethylene group
at this position, but the presence of ›N w NO2
significantly reduces affinity for the receptor (Liu
et al., 1993b; Tomizawa and Yamamoto, 1993;
Yamamoto et al., 1998). This suggests that the
reduction in binding, resulting from the presence of
the nitrogen atom at the 2-position, is compensated
by the increase in hydrophobicity, which enhances
transport to the target sites (Yamamoto et al., 1998;
Matsuda et al., 2001). Compared with nithiazine,
the biological efficacy of imidacloprid against the
green rice leafhopper could be enhanced 125-fold.
Furthermore, imidacloprid is about 10 000-fold
more insecticidal than (S)-nicotine, a natural insecticide
(Tomizawa and Yamamoto, 1993; Yamamoto
et al., 1995). This breakthrough to the novel systemic
insecticide imidacloprid was achieved by coupling
a special heterocyclic group, the 6-chloro-pyrid-3ylmethyl
(CPM) residue (Figure 4), to the 2-(Nnitroimino)-imidazolidine
building-block, new in
this class of chemistry.
With the introduction of the insecticide imidacloprid
to the market in 1991 Bayer AG began a successful
era of the so-called CNI TM s (chloronicotinyl
insecticides syn. neonicotinoids), a milestone in
insecticide research. Imidacloprid has, in the last
decade, become the most successful, highly effective,
and best selling insecticide worldwide used for
crop protection and veterinary pest control.
In connection with these excellent results, a parallel
change to other electron-withdrawing substituents
like 2-N-cyanoimino, having essentially shorter
maximum electronic absorptions than 290 nm, led to
the discovery of thiacloprid (see Section 3.3.1.2), a
second member of the CNI group. Attracted by
Bayer’s success with imidacloprid, several different
companies such as Takeda (now Sumitomo Chemical
Takeda Agro), Agro Kanesho, Nippon Soda, Mitsui
Toatsu (now Mitsui Chemicals, Inc.), Ciba Geigy
(now Syngenta), and others initiated intensive
research and developed their own neonicotinoid
insecticides. Research in these companies was
facilitated because neonicotinoid chemistry showed
a relatively broad spectrum of activity (Wollweber
and Tietjen, 1999; Roslavtseva, 2000). Since the market
introduction of imidacloprid, neonicotinoids
have become the fastest-growing class of chemical
insecticides. This tremendous success can be
explained by their unique chemical and biological
properties, such as broad-spectrum insecticidal activity,
low application rates, excellent systemic characteristics
such as uptake and translocation in plants,
new mode of action, and favorable safety profile.
3.3. Chemical Structure of
Neonicotinoids
In general, all these commercialized or developed
compounds can be divided into ring systems