CROP PROTECTION RESEARCH
698
CHIMIA 2003, 57, No.11
garding process chemistry follows. The last responding C-aryl compounds (Fig. 2).
part deals with the new mode of action of
tution patterns were screened. The 2,4,6-
Interestingly the herbicidal activity of trimethyl-phenyl (‘mesityl’) compounds 3
these compounds and their great value to the 2,4-dichloro derivative 2 switched from and their acylated derivatives 3A showed
farmers resulting from the high activity the original broad activity of compound 1 to an improved acaricidal activity against
against resistant mites and whiteflies activity against grassy weeds. Biochemical Tetranychus urticae, but were not satisfac-
worldwide.
work showed that we had a new class of tory regarding another important mite
herbicides acting on the acetyl CoA car- species, Panonychus ulmi.
boxylase (ACCase) in our hands, a target To improve this Panonychus activity a
well known from the commercial cyclo- broad screening of the substitution on the
Discovery
hexanedions (DIM) and aryloxyphe- ‘left side’ of the lead structures was per-
In the course of a synthesis program in noxypropionate (FOP) herbicides [3].
the area of bicyclic N-aryl PPO herbicides
formed. The monocyclic dimethyl-deriva-
Even more surprisingly the acylated de- tives of type 4 and 4A showed good activi-
of type 1 with activity against broad-leaved rivative 2A showed an acaricidal activity ty against both relevant mite species, but
weeds the central nitrogen atom was re- against Tetranychus urticae. To improve caused phytotoxic effects in some crops.
placed by a carbon atom leading to the cor- this activity many different aromatic substi-
To overcome this drawback the core
structures of the molecules were modified.
The synthesis of the tetronic acid analogues
5 and especially the acylated analogues like
e.g. the pivaloyl derivative 5A showed a
high acaricidal potential together with an
improved plant compatibility [4].
Cl
OR
F
O
O
Cl
N
CN
N
N
O
X
In some sensitive crops however, like
stone fruits or grapes, we still observed
phytotoxic effects under special conditions.
Therefore, in a ‘back to the roots’approach,
we changed the mesityl substitution pattern
back to the dichloro-type examined earlier
in the program. This led to the enol 6 as a
template that combined good acaricidal ac-
tivity against both mite species and a good
plant compatibility in all relevant crops.
The ‘fine tuning’ of these properties was
achieved by scanning a large set of differ-
ent acylating reagents – the optimum was
the 2,2-dimethyl-butyric acid derivative 7,
which was selected for development
under the common name spirodiclofen
(BAJ2740, trade name: Envidor®) [1].
During the acaricidal optimisation
process it was noticed that several com-
pounds, especially acylated 3-mesityl
tetronic acids with a spiro cyclopentyl ring
in position 5, showed additional excellent
activity against white flies (Bemisia
tabaci). The fine-tuning process regarding
activity, spectrum and plant compatibility
finally led to the 3,3-dimethyl-butyric acid
derivative spiromesifen (8) (BSN2060,
trade name: Oberon®) [2].
1
2
R=H
2A R=CO-CMe2-iPr
Me
Me
Me
Me
OR
OR
Me
Me
Me
Me
N
HN
O
R=H
O
3
4
R=H
3A R=CO-tBu
4A R=CO2-CH(Me)Et
Me
Me
Cl
OR
OH
Me
Cl
O
O
O
O
5
R=H
6
5A R=CO-tBu
Some physicochemical properties of the
new products are given in Fig. 2. Both have
a relatively high partition coefficient logP
(octanol/water) in the range of 4.5 to 5.8
and a low solubility in water of approxi-
mately 0.1 mg/l . Therefore after applica-
tion on plants they mainly stay on the leaf
and in the wax cuticle and are not systemic.
The X-ray structure analysis shows that
both compounds crystallise in a monoclin-
ic cell, Spirodiclofen (7) with the space
group P21/n and spiromesifen (8) P21/c
(Fig. 3). The torsion angles between the
tetronic acid ring and the 3-phenylring are
in the range of 50–60°, mainly due to steric
O
O
Cl
Me
O
O
O
O
Cl
Me
O
O
Me
7 (Spirodiclofen)
8 (Spiromesifen)
logPow
melt.point 95°C
water sol. 0.05 mg/l
5,83
logPow
melt.point 98°C
water sol. 0.13 mg/l
4.55
Fig. 2. Discovery of spirodiclofen (7) and spiromesifen (8)