Note: Descriptions are shown in the official language in which they were submitted.
CA 02569657 2006-12-19
30604-12D
- 1 -
FUNGICIDAL COMPOSITION BASED ON METALAXYL AND FAMOXADONE
This is a divisional application of Canadian
Patent Application 2,280,809, filed on March 3, 1998.
The present invention relates to fungicidal two-
s component mixtures having an unexpectedly enhanced activity
that are based on metalaxyl having an R-enantiomer content
of more than 70 % by weight, and to the use of those
mixtures in the control and prevention of infestation by
Oomycetes. The metalaxyl component is referred to as active
ingredient I.
The mixing partner II is one of the following
fungicides:
IIA) 4- [3- (4-chlorophenyl) -3- (3, 4-
dimethoxyphenyl)acryloyl]morpholine ("dimethomorph") (The
Pesticide Manual, 10th Ed., pages 351-2, 1994), or
IIB) 3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-
oxazolidine-2,4-dione ("famoxadone") (Brighton Crop
Protection Conference, Pests & Diseases 1996, Vol. I,
pages 21-26). It is also possible to use salts or metal
complexes of compounds IIA or IIB, for example copper or
manganese salts.
The subject matter of this divisional application
is directed to the mixture, and to use of the mixture,
wherein the mixing partner is famoxadone (IIB). The subject
matter of the parent application was restricted to the
mixture, and to use of the mixture, wherein the mixing
partner is dimethomorph (IIA). However, it should be
understood that the expression "the invention" and the like
when used herein encompass the subject matter of both the
parent and this divisional application.
CA 02569657 2006-12-19
30604-12D
- 1a -
In the narrower sense, the invention relates to
mixtures of pure metalaxyl having an R-enantiomer content of
more than 85 o by weight, especially more than 92 % by
weight, or more especially more than 95 o by weight. The
best results are achieved with pure R-enantiomer that is
substantially free of S-enantiomer.
Metalaxyl is methyl N-(2,6-dimethylphenyl)-N-
(methoxyacetyl)-DL-alaninate and has the structure
CH3 CH3
/ \ NCH-COOCH3
N
~C=O
CHZ
CH3 ~OCH3
It has an asymmetrical *C atom and can be
separated into the enantiomers in conventional manner
(GB-1 500 581). Since 1975 it has been known by experts in
the field that the
CA 02569657 2006-12-19
-2-
fungicidal action of the R-enantiomer far exceeds that of the S-enantiomer,
and the
R-enantiomer is in practice considered to form the true active principle.
Commercial
metalaxyl is available in the form of a racemate. A need to resolve the
racemate, half of
which consists of the desired R-enantiomer, has never arisen in the past for
practical
reasons.
Completely surprisingly, it has now been found that R-metalaxyl in pure form,
or in a form
concentrated to more than 70 % in the racemate, in co-operation with one of
the fungicidal
partners IIA or IIB, achieves unexpectedly high enhanced effects, some of
which exceed
the effects of the racemate-based mixtures (for example mentioned in EP-280
348 or
EP-393 911 ) by factors of up to 10. Factors that might have been expected,
based on the
R-enantiomer content of th a racemate being approximately 50 %, would be 2 at
most.
With this completely unexpected result, the present invention represents a
very substantial
enrichment of the art and a possibility of reducing the total rates of
application of fungicides
used in the control of Oomycetes on plants, thereby safeguarding the environ
ment. The
dramatically improved degradability of metalaxyl in the soil as soon as the R -
enantiomer
content exceeds 70 % by weight is known from WO-96/01559.
In addition to the two-component mixture I:II, the present invention relates
also to a method
of controlling fungi which comprises treating a site, for example a plant,
infested by or at
risk of infestation by fungi with a) component I and b) the compound II in any
order or
simultaneously.
Favourable I:II mixing ratios of the two compounds are from 30:1 to 1:30,
especially from
10:1 to 1:10, more especially from 10:1 to 1:5. In many cases, mixtures in
which the mixing
ratio of compound I to compound If is from 1:1 to 1:5 are advantageous.
The compound mixtures I+II according to the invention have very advantageous
curative,
preventive and systemic fungicidal properties for the protection of cultivated
plants. With the
compound mixtures of the invention it is possible to inhibit or destroy the
microorganisms
that occur on plants or parts of plants (the fruit, blossom, leaves, stems,
tubers or roots) of
various crops of useful plants, while the parts of plants that grow later are
also protected
CA 02569657 2006-12-19
-3-
from such microorganisms. This applies especially also to microorganisms that
have
developed reduced sensitivity to metalaxyl,
The mixtures of compounds I and II are usually used in the form of composi
tions.
R-metalaxyl (I) and the compound II may be applied simul taneously or directly
one after the
other to the area or plant to be treated, if desired together with further
carriers, surfactants
or other application-promoting additives that are customary in formulation
technology.
Suitable carriers and additives may be solid or liquid and are substances that
are expedient
in formulation technology, for example natural or regenerated mineral
substances, solvents,
dispersing agents, wetting agents, tackifiers, thickening agents, binders or
fertilisers.
A preferred method of applying a compound mixture that comprises at least one
each of the
compounds I and II is application to the parts of the plant above the soil,
especially the
leaves (foliar application). The frequency and rate of application depend on
the biological
and climatic living conditions for the pathogen in question. The compounds may
also
penetrate the plant through the root system via the soil (systemic action) as
a result of
impregnation of the locus of the plant with a liquid preparation or by means
of introduction
of the compounds into the soil in solid form, for example in the form of
granules (soil
application).
The compounds of the combination are used in unmodified form or preferably
together with
the adjuvants conventionally employed in formulation technology and are
accordingly
formulated in known manner, for example, into emulsifiable concentrates,
coatable pastes,
directly sprayable or dilutable solutions, dilute emulsions, wettable powders,
soluble
powders, dusts or granules, or by encapsulation in substances, for example
polymeric
substances. As with the nature of the compositions, the methods of
application, such as
spraying, atomising, dusting, scattering, coating or pouring, are chosen in
accordance with
the intended objectives and the prevailing circumstances. Favourable rates of
application of
the compound mixture are generally from 50 g to 1800 g of active ingredient
(a.i.) per
hectare (ha), especially from 100 g to 1000 g a.i./ha.
CA 02569657 2006-12-19
-4-
The formulations are prepared in known manner, e.g. by intimately mixing
and/or grinding
the active ingredients with extenders, such as solvents, solid carriers and,
where
appropriate, surface-active compounds (surfactants).
The agrochemical compositions usually contain 0.1 to 99 % by weight,
especially 0.1 to
95 % by weight of compounds of formulae ( and 11, 99.9 to 1 % by weight,
especially 99.9 to
% by weight of a solid or liquid adjuvant, and 0 to 25 % by weight, especially
0.1 to 25
by weight of a surfactant.
Whereas commercial products are preferably formulated as concentrates, the end
user will
normally employ dilute formulations.
Suitable target crops are especially potatoes, vines, hops, maize, sugar beet,
tobacco,
vegetables (tomatoes, paprika, lettuce etc.), and also bananas, rubber, lawn
grasses and
ornamental plants. Other plants endangered by downy mildew are known, inter
alia, from
the literature on metalaxyl.
The following Examples serve to illustrate the invention, "active ingredient"
denoting a
mixture of metaiaxyl (having an R-metalaxyl content of more than 95 % by
weight) and
compound II in a particular mixing ratio.
Wettable powders ~ a) b) c)
active ingredient [I:IIA
= 1:1 (a),
1:10(b); I:IIB = 1:5(c)] 26 44 % 72
%
sodium lignosulfonate 5 % 5 % -
sodium lauryl sulfate 3 % - 5
sodium diisobutylnaphthalene- 6 % 10
sulfonate
octylphenol polyethylene - 2 % -
glycol ether
(7-8 mol of ethylene oxide)
highly dispersed silicic 6 % 13 % 13
acid
kaolin 60 30 % -
%
CA 02569657 2006-12-19
-5-
The active ingredient is mixed thoroughly with the adjuvants and the mixture
is thoroughly
ground in a suitable mill, affording wettable powders which can be diluted
with water to give
suspensions of any desired concentration.
Emulsifiable concentrate
active ingredient (I:IIA 12
or IIB = 2:1 )
octylphenol polyethylene 3
glycol ether
(4-5 mol of ethylene oxide)
calcium dodecylbenzenesulfonate3
castor oil polyglycol ether 4
(35 mol of ethylene oxide)
cyclohexanone 30
xylene mixture 48
Emulsions of any desired dilution that can be used in plant protection can be
obtained from
this concentrate by dilution with water.
Extruder Granules
active ingredient (I:IIA =1:1 ) 16
sodium lignosulfonate 2
carboxymethylcellulose 1
kaolin 81
The active ingredient is mixed and ground with the adjuvants, and the mixture
is moistened
with water. The mixture is extruded and then dried in a stream of air.
Coated cLranules
active ingredient (I:IIB = 10:1 ) 11
polyethylene glycol (mol. wt. 200) 3
kaolin 86
The finely ground active ingredient is uniformly applied, in a mixer, to the
kaolin moistened
with polyethylene glycol. Non-dusty coated granules are obtained in this
manner.
CA 02569657 2006-12-19
-6-
Suspension concentrate
active ingredient (I:IIA or IIB = 1:10) 44
propylene glycol 10
nonylphenol polyethylene glycol ether 6
(15 mol of ethylene oxide)
sodium lignosulfonate 10
carboxymethylcellulose 1
silicone oil (in the form of a 75
aqueous emulsion) 1
water 28
The finely ground active ingredient is intimately mixed with the adjuvants,
giving a
suspension concentrate from which suspensions of any desired dilution can be
obtained by
dilution with water. Using such dilutions, living plants can be treated and
protected from
infestation by microorganisms by spraying, watering or immersion.
Biological Examples
Example 1) Action against Plasmopara viticola on vines
Vine seedlings of the Gutedel variety are grown under greenhouse conditions
(20-24 °C) to
the 4- to 5-leaf stage (3 weeks). Disks 10 mm in diameter are then cut from
the leaves. The
leaf segments are placed on Petri dishes with their upper side facing
downwards. The
dishes contain 1.8 ml water/0.16 % agar. The fungicides are added to
demineralised water
and diluted appropriately. The fungicidal treatment is carried out one day
before the inocula-
tion. The entire leaf surface disk is then uniformly sprayed to drip point
with a freshly
prepared sporangia suspension (50 000-60 000/m1) of Plasmopara viticola. The
plants are
subsequently kept in a controlled environment chamber for 7 days at 18
°C and approx-
imately 100% relative humidity with artificial daylight of 12 hours' duration
(3000 lux).
Evaluation of the infestation is then carried out.
The percentage leaf infestation is assessed and the percentage action relative
to the control
is calculated. The comparison between the percentage action of the mixture R-
metalaxyl
CA 02569657 2006-12-19
(>95 % by weight)/famoxadone and the mixture metalaxyl(rac.)/famoxadone gives
the
comparison factor.
R-metalaxyl Famoxadone Mixing Activity of Activity of Comparison
>95 % by wt. ratio R-metalaxyl metalaxyl factor
or I:II (95%) plus (rac.) plus
metalaxyl famoxadone famoxadone
(racemate)
mg a.!./1 mg a.!./1
0.1 0.1 1:1 29.1 3.1 9.5
0.1 0.5 1:5 52.7 14.9 3.5
0.1 1 1:10 52.7 22.0 2.4
Example 2) Action against Phyto~hthora infestans on tomatoes
Tomato plants of the variety cv.Baby are grown individually in flower pots
(diameter = 8 cm)
under greenhouse conditions for 4 weeks. The plants are then sprayed with
active
ingredient formulation prepared from an emulsifiable concentrate. 3 plants are
used in each
case. The entire leaf surface of the lower leaves of the plant are then
uniformly sprayed with
a freshly prepared sporangia suspension (80 000/m1) of Phytophthora infestans
. The plants
are subsequently kept for 2 days at 15 °C and approximately 100 %
relative humidity with
artificial daylight of 16 hours' duration and then for a further 5 days at 15
°C and 60
relative humidity. Evaluation of the infestation is then carried out.
The percentage leaf infestation is assessed and the percentage action relative
to the control
is calculated. The comparison between the percentage action of the mixture R-
metalaxyl
(>95% by weight)/dimethomorph and the mixture metalaxyl (rac.)/dimethomorph
gives the
comparison factor.
CA 02569657 2006-12-19
_8-
R-metalaxylDimethomorph Mixing Activity Activity Comparison
of of
>95 % by mg a.i./I ratio R-metalaxyl metalaxyl factor
wt.
or I:II (95%) plus (rac.)
plus
metalaxyl dimetho- dimetho-
racemate morph morph
mg a.i./I
0.25 0.25 1:1 86.0 16.0 5.3
0.25 0.5 1:2 87.0 39.0 2.2
