Note: Descriptions are shown in the official language in which they were submitted.
CA 02571911 2007-O1-10
1
FUNGICIDE MIXTURES BAQSED ON PYRiDiNE CARBOXRMIDES
This application is a division of Canadian application 2,312,993 deriving from
international application n° PCT/EP98108230 filed on December 15, 1998.
The present invention relates to fungicidal mixtures for
controlling harmful fungi and also to methods for controlling
harmful fungi using such mixtures.
WO 97/08952 describes mixtures of amide compounds of the
formula I
A-CO-NR1R2 (I)
in which
A is an aryl group or an aromatic or non-aromatic, 5- or
6-membered heterocycle which has from 1 to 3 heteroatoms
selected from O, N and S;
where the aryl group or the heterocycle may or may not have
1, 2 or 3 substituents which are selected, independently of
one another, from alkyl, halogen, CHF2, CF3, alkoxy,
haloalkoxy, alkylthio, alkylsulfynyl and alkylsulfonyl;
R1 is a hydrogen atom;
R2 is a phenyl or cycloalkyl group which may or may not have 1,
2 or 3 substituents which are selected from alkyl, alkenyl,
alkynyl, alkoxy, alkenyloxy, alkynyloxy, cycloalkyl,
cycloalkenyl, cycloaikyloxy, cycioaikenyioxy, phenyl and
halogen, where the aliphatic and cycloaliphatic radicals may
be partially or fully halogenated and/or the cycloaliphatic
radicals may be substituted by from 1 to 3 alkyl groups and
where the phenyl group may have from 1 to 5 halogen atoms
and/or from 1 to 3 substituents which are selected,
independently of one another, from alkyl, haloalkyl, alkoxy,
haloalkoxy, alkylthio and haloalkylthio, and where the amidic
phenyl group may or may not be condensed with a saturated
5-membered ring which may or may not be substituted by one or
more alkyl groups and/or may have a heteroatom selected from
3o O and S, and the active ingredient fenazaquin which is known
as an acaricide.
These mixtures are described as being particularly effective
against Botrytis.
CA 02571911 2007-O1-10
2
It is an object of the present invention to provide a
particularly effective mixture for controlling harmful fungi,
in particular for certain indications.
More specifically, the present invention as broadly described hereinafter is
directed to a fungicidal mixture which comprises as active ingredients an
amide
compound of the formula I defined above and one of more further fungicidaliy
active components selected from the group consisting of
b) a carboxamide II selected from the group of the compounds IIa
and IIb
CI
/ \
O
C~ CH-C-N 0 (IIa)
U
/ \
CH30 OCH3
II
CH3
F3C ~ \ C-.-_
CHZCH3
\\ (11b)
CH30 OCH3
c) a valinamide of the formula III
H3C-CH -CH3
H3 ( III )
8130 -C- NH -CH-C- NH-CH-R14
in which
R13 is C3-C4-alkyl and
CA 02571911 2007-O1-10
3
R14 is naphthyl or phenyl, where the phenyl radical in the
4-position is substituted by a halogen atom, a
C1-C4-alkyl or a C1-C~-alkoxy group,
d) at least one active ingredient. of the formulae IV.1 to IV. S,
O CH3 O
_ ~~ ~ ~~ O
CHz- C ~ / CH C02 CH3 CICH2 - C
N N O
H3C ~ \ CH3 HsC ~ \ CHa
15 / /
(IV.1)
(IV.2.)
O CH3 0 CHa
CH3 O CH2 - C ~ / CH C02 CH3 ~ ~ C / CH CO2 CH;,
N ~ N
H3C ~ CH3 H3C \ CH3
/ ~ /
(IV.3) (IV.4}
0
~O
CH30CH2- C
35 ~ N O
H3C \ CH3
/
(IV.S)
and
45
c) the 1-(2-cyano-2-methoxyiminoacetyl)-3-ethylurea
of the formula (V)
CA 02571911 2007-O1-10
4
HgCCH2-~~l-ICO!'JH-C(CN)=~OCH3 v
in a synergistically effective amount.
The present invention as claimed is however restricted to a fungicidal mixture
comprising as active components
a) an amide compound of the formula I
A-C4-N R 1 R2 I
in which
A is pyridyl which is unsubstituted or carries 1, 2 or 3 substituents selected
from
the group consisting of alkyl, halogen, CHF2, CF3, alkoxy, haloalkoxy,
alkylthio,
alkylsulfynyl and alkylsulfonyl;
R1 is hydrogen;
R2 is phenyl which optionally carries 1, 2 or 3 substituents selected from the
group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy,
cycloalkyl, cycloalkenyl, cycloalkyloxy, cycloalkenyloxy, phenyl and halogen,
where the aliphatic and cycloaliphatic radicals are unsubstituted, partially
or fully
halogenated and the cycloaliphatic radicals optionally carry from 1 to 3 alkyl
groups, and where the phenyl group is unsubstituted or substituted by from 1
to
5 halogen atoms and/or from 1 to 3 substituents selected from the group
consisting of: alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio and
haloalkylthio, and
where the amidic phenyl group is optionally condensed with a saturated 5-
membered ring which is unsubstituted or substituted by one or more alkyl
groups, and
d) at least one compound of the formula IV.1 to IV.5 as defined hereinabove,
CA 02571911 2007-O1-10
4a
wherein the active components are present in sy'ner gistically effective
amounts.
The composition as claimed may also comprise at least one additional
ingredient selected from those identified as (c) and (e) herein above.
The mixtures according to the invention have synergistic action
and are therefore particularly suitable for controlling harmful
fungi and in particular downy mildew fungi in vegetables and
grapevines.
In the context of the present invention, halogen is fluorine,
'10 chlorine, bromine and iodine and is in particular fluorine,
chlorine and bromine.
The term "alkyl" includes straight-chain and branched alkyl
groups. These are preferably straight-chain or branched
C1-Clz-alkyl and in particular C1-C6-alkyl groups. Examples of
alkyl groups are alkyl such as, in particular, methyl, ethyl,
propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl,
1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl,
3-methylbutyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl,
2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1-methylpentyl,
2-methylpentyl, 3-methylpentyl, 4-methylpentyl,
1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl,
1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl,
20 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethylbutyl,
2-ethylbutyl, 1-ethyl-2-methylpropyl, n-heptyl, 1-methylhexyl,
1-ethylpentyl, 2-ethylpentyl, 1-propylbutyl, octyl, decyl,
dodecy 1.
Haloalkyl is an alkyl group as defined above which is partially
or fully haloger~ated by one or more halogen atoms, in particular
by fluorine and chlorine. Preferably, there are from 1 to 3
halogen atoms present, and the difluoromethane or the
trifluoromethyl group is particularly preferred.
The above statements for the alkyl group and the haloalkyl group
apply in a corresponding manner to the alkyl and haloalkyl groups
30 in alkoxy, haloalkoxy, alkylthio, haloalkylthio, alkylsulfynyl
and alkylsulfonyl.
CA 02571911 2007-O1-10
4b
The alkenyl group includes straight-chain and branched alkenyl
groups. These are preferably straight-chain or branched
C3-C1z-alkenyl groups and in particular C3-C6-alkenyl groups.
Examples of alkenyl groups are 2-propenyl, 2-butenyl, 3-butenyl,
1-methyl-2-propen;l, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl,
4-pentenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl,
CA 02571911 2007-O1-10
3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl,
3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl,
1,2-dimethyl-2-propenyl, 1-ethyl-2-propenyl, 2-hexenyl,
3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-2-pentenyl,
5 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl,
1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl,
4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl,
3-methyl-4-pentenyl, 4-methyl-4-pentenyl, '_,1-dimethyl-2-butenyl,
1,1-dimethyl-3-butenyl, 1,1-dimethyl-3-butenyl [sic],
ZO 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl,
1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl,
2,2-dimethyl-3-butenyl, 2,3-dimethyl-2-butenyl,
2,3-dimethyl-3-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl,
2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl,
1-ethyl-1-methyl-2-propenyl and 1-ethyl-2-methyl-2-propenyl, in
particular 2-propenyl, 2-butenyl, 3-methyl-2-butenyl and
3-methyl-2-pentenyl.
The alkenyl group may be partially or fully halogenated by one or
more halogen atoms, in particular by fluorine or chlorine. This
group preferably has from 1 to 3 halogen atoms.
The alkynyl group includes straight-chain and branched alkynyl
groups. These are preferably straight-chain and branched
C3-C12-alkynyl groups and in particular C3-C6-alkynyl groups.
Examples of alkynyl groups are 2-progynyl, 2-butynyl, 3-butynyl,
1-methyl-2-propynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl,
1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-methyl-2-butynyl,
I~1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 2-hexynyl,
3-hexynyl, 4-alkynyl [sic], 5-hexynyl, 1-methyl-2-pentynyl,
1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl,
2-methyl-4-pentynyl, 3-methyl-4-pentynyl, 4-methyl-2-pentynyl,
1,2-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl,
1~2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl,
1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl and
1-ethyl-1-methyl-2-propynyl.
The above statements for the alkenyl group and its halogen
substituents and for the alkynyl group apply in a corresponding
manner to alkenyloxy and alkynyloxy.
The cycloalkyl group is preferably a C3-C6-cycloalkyl group, such
as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. If th.e
cycloalkyl group is substituted, it preferably has from 1 to 3
C1-C4-alkyl radicals as substituents.
CA 02571911 2007-O1-10
6
Cycloalkenyl is preferably a Cq-C6-cycloalkenyl group, such a=
cyclobutenyl, cyclcpcntonyl cr cyclchexenyl. If the cycloalkenyl
group is substituted, it preferably has from 1 to 3 C1-CQ-alkyl
radicals as substituents.
A cycloalkoxy group is preferably a C5-C6-cycloalkoxy group, such
as cyclopentyloxy or cyclohexyloxy. If the cycloalkoxy group is
substituted, it preferably has from 1 to 3 C1-Cd-alkyl radicals as
substituents.
The cycloalkenyloxy group is preferably a C5-C6-cycloalkenyloxy
group, such as cyclopentyloxy or cyclohexyloxy. If the
cycloalkenyloxy group is substituted, it preferably has from 1 to
3 C1-C4-alkyl radicals as substituents.
Aryl is preferably phenyl.
If A is a phenyl group, this may have one, two or three of the
abovementioned substituents in any position. These substituents
are preferably selected, independently of one another, from
alkyl, difluoromethyl, trifluoromethyl and halogen, in particular
chlorine, bromine and iodine. Particularly preferably, the phenyl
group has a substituent in the 2-position.
If A is a 5-membered heterocycle, it is in particular a furyl,
thiazolyl, pyrazolyl, imidazolyl, oxazolyl, thienyl, triazolyl or
thiadiazolyl radical or the corresponding dihydro or tetrahydro
derivatives thereof. Preference is given to a thiazolyl or
pyrazolyl radical.
If A is a 6-membered heterocycle, it is in particular a pyridyl
radical or a radical of the formula:
C X~-
Y
in which one of the radicals X and Y is 0, S or NR1~, where R1~ is
H or alkyl, and the other of the radicals X and Y is CH2, S, SO,
SOZ or NR12. The dotted line means that a double bond may or may
not be present.
CA 02571911 2007-O1-10
7
The 6-membered aromatic heterocycle is particularly preferably a
pyridyl radical, in particular a 3-pyridyl radical, or a radical
of the formula
0 ~ CH3
(A3)
in which X is CH2, S, SO or S02.
The abovementioned heterocyclic radicals may or may not have I, 2
or 3 of the abovementioned substituents, where these substituents
are preferably selected, independently of one another, from
alkyl, halogen, difluoromethyl or trifluoromethyl.
A is particularly preferably a radical of the formulae:
/ 3 ~ i 4
R N R
(A1) (A2)
R8
R7 S
.N
N R6 R N
I
(A5) (A7) CH3
in which R3, R4, R6, R~, R8 and R9 independently of one another are
hydrogen, alkyl, in particular methyl, halogen, in particular.
chlorine, CHF2 or CF3.
The radical R1 in the formula I is preferably a hydrogen atom.
The radical Rz in the formula I is preferably a phenyl radical. R2
preferably has at least one substituent which is particularly
preferably in the 2-position. The substituent (or the
substituents) is (are) preferably selected from the group
consisting of alkyl, cycloalkyl, cycloalkenyl, halogen and
phenyl.
CA 02571911 2007-O1-10
8
The substituents of the radical RZ may in turn be substituted
again. The aliphatic or cycloaliphatic substituents may be
partially or fully halogenated, in particular fluorinated or
chlorinated. They preferably have 1, 2 or 3 fluorine or chlorine
atoms. If the substituent of the radical Rz is a phenyl group,
this group may preferably be substituted by from 1 to 3 halogen
atoms, in particular chlorine atoms, and/or by a radical which is
preferably selected from alkyl and alkoxy. Particularly
preferably, the phenyl group is substituted with a halogen atom
in the p-position, i.e. the particularly preferred substituent of
the radical R2 is a p-halogen-substituted phenyl radical. The
radical RZ may also be condensed with a saturated 5-membered ring,
where this ring for its part may have from 1 to 3 alkyl
substituents.
Rz is in this case, for example, indanyl, thiaindanyl and
oxaindanyl. Preference is given to indanyl and 2-oxaindanyl which
are attached to the nitrogen atom in particular via the
4-position.
According to a preferred embodiment, the composition according to
the invention comprises as amide compound a compound of the
formula I in which A is as defined below:
phenyl, pyridyl, dihydropyranyl, dihydrooxathiynyl,
dihydrooxathiynyloxide, dihydrooxathiynyldioxide, furyl,
thiazolyl, pyrazolyl or oxazolyl, where these groups may have 1,
2 or 3 substituents which are selected, independently of one
another, from alkyl, halogen, difluoromethyl and trifluoromethyl.
According to a further preferred embodiment, A is:
pyridin-3-yl, which may or may not be substituted in the
2-position by halogen, methyl, difluoromethyl, trifluoromethyl,
methoxy, methylthio, methylsulfynyl or methylsulfonyl;
phenyl, which may or may not be substituted in the 2-position by
methyl, trifluoromethyl, chlorine, bromine or iodine;
2-methyl-5,6-dihydropyran-3-yl;
2-methyl-5,6-dihydro-1,4-oxathiyn-3-yl or the 4-oxide or
4,4-dioxide thereof;
2-methylfuran-3-yl, which may or may not be substituted in the 4-
and/or 5-position by methyl;
CA 02571911 2007-O1-10
9
thiazol-5-yl, which may or may not be substituted in the 2-
and/or 4-position by methyl, chlorine, difluoromethyl or
trif luor vmetl-~y l ;
thiazol-4-yl, which may or may not be substituted in the 2-
and/or 5-position by methyl, chlorine, difluoromethyl or
trifluoromethyl;
1-methylpyrazol-4-yl, which may or may not be substituted in the
3- and/or 5-position by methyl, chlorine, difluoromethyl or
trifluoromethyl; or
oxazol-5-yl, which may or may not be substituted in the 2- and/or
4-position by methyl or chlorine.
According to a further preferred embodiment, the compositions
according to the invention comprise as amide compound a compound
of the formula I in which RZ is a phenyl group which may or may
not be substituted by 1, 2 or 3 of the abovementioned
substituents.
According to a further preferred embodiment, the compositions
according to the invention comprise as amide compound a compound
of the formula I in which RZ is a phenyl group which has one of
the following substituents in the 2-position:
C3-C6-alkyl, C5-C6-cycloalkenyl, C5-C6-cycloalkyloxy,
cycloalkenyloxy, where these groups may be substituted by 1, 2 or
3 C1-C4-alkyl groups,
phenyl, which is substituted by from 1 to 5 halogen atoms and/or
from 1 to 3 groups which are selected, independently of one
another, from C1-Cq-alkyl, C1-CQ-haloalkyl, C1-C4-alkoxy,
C1-C4-haloalkoxy, C1-C4-alkylthio and C1-C4-haloalkylthio,
indanyl or oxaindanyl which may or may not be substituted by 1, 2
or 3 C1-C4-alkyl groups.
According to a further preferred embodiment, the compositions
according to the invention comprise as amide compound a compound
of the formula Ia,
CA 02571911 2007-O1-10
1~
A-CO-NH
W
R1a
in which
A is
1 s ~ ~ I ~ ~ X~r
4
R3 N R CH3
(Al) (A2) (A3)
R5 R7 S N
R7 ~/
R5 O CH3 R5 S
(A4) (A5) (A6) Ra
R9 R5 ~ 0
N
CH3-N, ' 9
N R8 R
(A7) (A8)
X is methylene, sulfur, sulfynyl or sulfonyl (S02),
R3 is methyl, difluoromethyl, trifluoromethyl, chlorine, bromine
or iodine,
R4 is trifluoromethyl or chlorine,
R5 is hydrogen or methyl,
R6 is methyl, difluoromethyl, trifluoromethyl or chlorine,
R7 is hydrogen, methyl or chlorine,
R8 is methyl, difluoromethyl or trifluoromethyl,
R9 is hydrogen, methyl, dif luoromethyl, trifluoromethyl or
chlorine,
CA 02571911 2007-O1-10
11
R1~ is C1-CQ-alkyl, C1-CQ-alkoxy, C1-C4-alkylthio or halogen.
According to a particularly preferred embodiment, the
compositions comprise as amide compound a compound of the
formula Ib
CO-NH
I ~ I (Ib)
N R4 R11
in which
R4 is halogen and
R11 is phenyl which is substituted by halogen.
Particularly preferred mixtures according to the invention
comprise as component I compounds of the formulae
0
~i
i1 N \
H ~ I N
'N C1 ~ I ~ H
\ N C1
F
C1
0
I
N
H
'N C1
Useful amide compounds of the formula I are mentioned in EP-A-545
099 and 589 301 .
The preparation of the amide compounds of the formula I is known,
for example, from EP-A-545 099 or 589 301 or can be carried out
by similar processes.
CA 02571911 2007-O1-10
12
Also known are the carboxamides II [IIa: common name:
dimethomorph, EP-A 120 321; IIb: proposed common name:
flumetover, AGROW No. 243, 22 (.1°°S)~, their preparation and
their action against harmful fungi.
The compounds of the formula III are also known per se. A first
preferred group of valinamide derivatives are compounds of the
formula III'
15
0 \ H ~ X
/\N N I / (III')
8130 ~ U
H
O
in which R13 is as defined above and X is halogen, C1-C4-alkyl or
C1-C4-alkoxy. Compounds of this type and their preparation are
described, for example, in EP-A-0 610 764 and EP-A-0 398 072.
A further preferred group of valinamide derivatives are compounds
of the formula III "
30
J~ H , ,
N I / / (III" )
8130 N ~ \/ U
H
O
in which R13 is as defined above. Compounds of this type and their
preparation are described, for example, in DE-A-43 21 897 and
WO-A-96107638.
Preference is given to compounds of the formula III in which R13
is isopropyl, sec-butyl and tert-butyl.
Likewise, preference is given to compounds of the formula III in
which R14 is a-naphthyl, ~-naphthyl and phenyl, the phenyl radical
being substituted in the 4-position by chlorine, bromine,
C1-C4-alkyl or C1-C9-alkoxy.
Particular preference is given to compounds of the formula III in
which R14 is ~-naphthyl, 4-chlorophenyl, 4-methylphenyl and
4-methoxyphenyl.
CA 02571911 2007-O1-10
13
Preferred examples of valinamides which can be used according to
the invention are summarized in Table A below.
Table A
NO. R13 R14
III.1 isopropyl ~-naphthyl
III.2 isopropyl 4-chlorophenyl
III.3 isopropyl 4-methylphenyl
III.4 isopropyl 4-methoxyphenyl
III.S sec-butyl ~-naphthyl
III.6 sec-butyl 4-chlorophenyl
III.7 sec-butyl 4-methylphenyl
III.B sec-butyl 4-methoxyphenyl
III.9 tert-butyl ~-naphthyl
III.10 tert-butyl 4-chlorophenyl
III.11 tert-butyl 4-methylphenyl
III.12 tert-butyl 4-methoxyphenyl
Particular preference is given to the compounds III.2 and III.9.
From the structural formula for the compounds of the formula III
it is evident that these compounds have two asymmetrically
substituted carbon atoms. The compounds can therefore be used for
the mixture according to the invention either as mixtures of
different isomers or as pure isomers.
In a further preferred embodiment, compounds of the formula III
are used in which the a.~~ino acid moiety is formed by
alkoxycarbonyl-L-valine (S configuration) and the phenethylamine
moiety or the naphthylethylamine moiety has the R configuration.
Such compounds can be represented by the formula IIIa
0 H3C-CH-CH3
H H
8130 ~N~\C/N R14 (IIIa)
H H
0 CH3
(S) (R)
in which R13 and R14 are as defined for the compounds of the
formula II.
CA 02571911 2007-O1-10
14
The preparation of the preferred isomers of the formula IIIa is
carried out similarly to the methods described in the earlier
German patent application~. DE-A-195 31 814.
The isomerically pure compounds of the formula IIIa can be
prepared in a manner known per se starting from the appropriate,
L-valine-based carbamoylcarboxylic acids VI. The compounds IIIa
are obtained, for example, by the process described below in
which a carbamoylcarboxylic acid VI is reacted with an amine VII
(the literature references "Houben-Weyl" refer to: Houben-Weyl,
Methoden der Organischen Chemie, 4th edition, Thieme Verlag,
Stuttgart):
0 H3C-~ H-CH3 H
+ HzN\- / R1a ~ ( IIIa)
8130 /C\N/C\C/OH C
H H II
0 CH3
(VI) (VII)
The carbamoylcarboxylic acids VI are known or can be prepared by
known methods, in particular starting from the amino acid
L-valine (cf. "Houben-Weyl", volume 15/1, pp. 46-305, in
particular pp. 117-125).
The amines VII are also known or can be easily obtained (cf.
Organikum, VEB Deutscher Verlag der Wissenschaften, 15th edition,
Berlin, 1977, p. 610 ff.; "Houben-Weyl", volume 15/1, pp.
648-665; Indian J. Chem. 10, pp. 366 (1972); J. Am. Chem. Soc.
58, pp. 1808-1811 (1936)).
From racemates of the amines VII, the R isomer can be isolated in
a manner known per se, for example by fractional crystallization
using optically active tartaric acid or, preferably, by
enzyme-catalyzed esterification and subsequent hydrolysis (cf.,
for example, WO-A-95/08636).
This process is preferably carried out by initially converting
the carbamoylcarboxylic acids VI into carboxyl-ativaited
derivatives, in particular into acyl cyanides or anhydrides, (cf.
Tetrahedron Letters, volume 18, pp. 1595-1598 (1973), or
"Houben-weyl", volume 15/1, pp. 28-32). These derivatives are
then reacted with the amines VII in the presence of bases.
CA 02571911 2007-O1-10
Suitable for preparing the carboxyl-activaved acyl cyanides i.s,
for example, the reaction of the carbamoylcarboxylic acids v with
diethyl cyanophosphonate, in particular in an inert solvent, such
as tetrahydrofuran or toluene.
5
The preparation of the carboxyl-activiated anhydrides is
preferably carried out by reacting the carbamoylcarboxylic acid V
with chloroformates, such as isobutyl chloroformate, in the
presence of bases and, if appropriate, in an inert solvent, such
10 as toluene or tetrahydrofuran.
The reaction of the amines VII with the carboxyl-activated
carbamoylcarboxylic acids VI is preferably carried out in a
15 solvent such as dichloromethane, tetrahydrofuran or toluene.
The amines VII may also serve as bases, in which case they are
usually recovered from the crude product.
In a preferred embodiment of this process step, the
carbamoylcarboxylic acid VI, the amine VII, the reagent which is
suitable for generating the carboxyl-activated derivative of the
carbamoylcarboxylic acid VI and the base are reacted in a one-pot
process, if appropriate in an inert solvent, and the crude
product is subsequently worked-up in a manner known per se to
isolate the carbamoylcarboxamide IIIa.
The compound IV.1 is commercially available under the common name
benalaxyl or the trade name Galben~".
The compound IV.2 is commercially available under the common name
ofurace or the trade name Celtan"" P in the form of mixtures with
cymoxanil and folpet.
The compound IV.3 is commercially available under the common name
metalaxyl or the trade name Ridomil'".
The compound IV.4 is commercially available under the common name
furalaxyl or the trade name Fongaride~".
The compound of the formula IV.S is commercially available under
the common name oxadixyl and under the trade name Sandofan""C in
mixtures with copper salts.
CA 02571911 2007-O1-10
16
Processes for preparing the compounds of the formula IV are known
per se to the person skilled in the art, and there is therefore
no iie2d t0 iu2I"itlGit them here in any detail.
The compound V (US-A 3,957,847; common name: cymoxanil), its
preparation and its action against harmful fungi are also known.
To unfold the synergistic activity, even a small amount of amide
compound of the formula I is sufficient. Preference is given to
employing amide compound and compounds II and/or the compounds
III to V in a weight ratio in the range of from 20:1 to 1:20, in
particular 10:1 to 1:10.
When preparing the mixtures, it is preferred to employ the pure
active ingredients I and II and/or III to V, to which further
active ingredients against harmful fungi or other pests, such as
insects, arachnids or nematodes, or else herbicidal or growth-
regulating active ingredients or fertilizers can be admixed.
The mixtures of the compounds I and II and/or III to V, or the
compounds I and II and/or III to V used simultaneously, jointly
or separately, exhibit outstanding activity against a wide range
of phytopathogenic fungi, in particular from the classes of the
Ascomycetes, Basidiomycetes, Phycomycetes and Deuteromycetes.
Some of them act systemically and can therefore also be employed
as foliar- and soil-acting fungicides.
They are especially important for controlling a large number of
fungi in a variety of crop plants, such as cotton, vegetable
species (eg. cucumbers, beans, tomatoes, potatoes and cucurbits),
barley, grass, oats, bananas, coffee, maize, fruit species, rice,
rye, seya, grapevine, wheat, ornamentals, sugar cane, and a
variety of seeds.
They are particularly suitable for controlling the following
phytopathogenic fungi: Erysiphe graminis (powdery mildew) in
cereals, Erysiphe cichoracearum and Sphaerotheca fuliginea in
cucurbits, Podosphaera leucotricha in apples, Uncinula necator in
grapevines, Puccinia species in cereals, Rhizoctonia species in
cotton, rice and lawns, Ustilago species in cereals and sugar
cane, Venturia inaequalis (scab) in apples, Helminthosporium
species in cereals, Septoria nodorum in wheat, Botrytis cinera
(gray mold) in strawberries, vegetables, ornamentals and
grapevines, Cercospora arachidicola in groundnuts,
Pseudocercosporella herpotrichoides in wheat and barley,
Pyricularia oryzae in rice, Phytophthora infestans in potatoes
CA 02571911 2007-O1-10
17
and tomatoes, Plasmopara viticola in grapevines,
Pseudoperonospora species in hops and cucumbers, Alternaria
species in vegetables and fruit, Mycosphaerella species in
bananas and Fusarium and Verticillium species.
The mixtures according to the invention may particularly
preferably be employed for controlling powdery mildew fungi in
vegetables and grapevines.
The compounds I and II and/or III to V can be applied
simultaneously, either together or separately, or in succession,
the sequence, in the case of separate application, generally not
having any effect on the result of the control measures.
20
Depending on the kind of effect desired, the application rates of
the mixtures according to the invention are, in particular in
agricultural crop areas, from 0.01 to 8 kg/ha, preferably from
0.1 to 5 kg/ha, in particular from 0.5 to 3.0 kg/ha.
The application rates of the compounds I are from 0.01 to 2.5
kg/ha, preferably from 0.05 to 2.5 kg/ha, in particular from 0.1
to 1.0 kg/ha.
correspondingly, in the case of the compounds II and/or III to V,
the application rates are from 0.01 to 10 kg/ha, preferably from
0.05 to 5 kg/ha, in particular from 0.05 to 2.0 kg/ha.
For seed treatment, the application rates of the mixture are
generally from 0.001 to 250 g/kg of seed, preferably from 0.01 to
100 g/kg, in particular from 0.01 to 50 g/kg.
If phytopathogenic harmful fungi are to be controlled, the
separate or joint application of the compounds I and II and/or
III to V or of the mixtures of the compounds I and II and/or III
to V is effected by spraying or dusting the seeds, the plants or
the soils before or after sowing of the plants, or before or
after plant emergence.
The fungicidal synergistic mixtures according to the invention,
or the compounds I and II and/or III to V, can be formulated for
example in the form of ready-to-spray solutions, powders and
suspensions or in the form of highly concentrated aqueous, oily
or other suspensions, dispersions, emulsions, oil dispersions,
pastes, dusts, materials for broadcasting or granules, and
applied by spraying, atomizing, dusting, broadcasting or
CA 02571911 2007-O1-10
18
watering. The use form depends on the intended purpose; in any
case, it should ensure as fine and uniform as possible a
distribution of the mixture according to the invention.
The formulations are prepared in a known manner, eg. by extending
the active ingredient with solvents and/or carriers, if desired
using emulsifiers and dispersants, it being possible also to use
other organic solvents as auxiliary solvents if water is used as
the diluent. Suitable auxiliaries for this purpose are
essentially: solvents such as aromatics (eg. xylene), chlorinated
aromatics (eg. chlorobenzenes), paraffins (eg. mineral oil
fractions), alcohols (eg. methanol, butanol), ketones (eg.
cyclohexanone), amines (eg. ethanolamine, dimethylformamide) and
water; carriers such as ground natural minerals (eg. kaolins,
clays, talc, chalk) and ground synthetic minerals (eg. finely
divided silica, silicates); emulsifiers such as nonionic and
anionic emulsifiers (eg. polyoxyethylene fatty alcohol ethers,
alkylsulfonates and arylsulfonates) and dispersants such as
lignosulfite waste liquors and methylcellulose.
Suitable surfactants are the alkali metal salts, alkaline earth
metal salts and ammonium salts of aromatic sulfonic acids, eg.
ligno-, phenol-, naphthalene- and dibutylnaphthalenesulfonic
acid, and of fatty acids, alkyl- and alkylarylsulfonates, alkyl,
lauryl ether and fatty alcohol sulfates, and salts of sulfated
hexa-, hepta- and octadecanols, or of fatty alcohol glycol
ethers, condensates of sulfonated naphthalene and its derivatives
with formaldehyde, condensates of naphthalene or of the
naphthalenesulfonic acids with phenol and formaldehyde,
polyoxyethylene octylphenol ether, ethoxylated isooctyl-, octyl-
or nonylphenol, alkylphenol polyglycol ethers, tributylphenyl
polyglycol ethers, alkylaryl polyether alcohols, isotridecyl
alcohol, fatty alcohol/ethylene oxide condensates, ethoxylated
castor oil, polyoxyethylene alkyl ethers or polyoxypropylene
[sic), lauryl alcohol polyglycol ether acetate, sorbitol esters,
lignosulfite waste liquors or methylcellulose.
Powders, materials for broadcasting and dusts can be prepared by
mixing or jointly grinding the compounds I or II and/or III to V,
or the mixture of the compounds I and II and/or III to V, with a
solid carrier.
Granules (eg. coated granules, impregnated granules or
homogeneous granules) are usually prepared by binding the active
ingredient, or active ingredients, to a solid carrier.
CA 02571911 2007-O1-10
19
Fillers or solid carriers are, for example, mineral earths, such
as silica gel, silicas, silica gels, silicates, talc,
kaolin, limestone, lime, chalk, bole, loess, clay, dolomite,
diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium
oxide, ground synthetic materials, and fertilizers such as
ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas,
and products of vegetable origin, such as cereal meal, tree bark
meal, wood meal and nut-shell meal, cellulose powders or other
solid carriers.
The formulations generally comprise from 0.1 to 95~ by weight,
preferably from 0.5 to 90$ by weight, of one of the compounds I
or II or of the mixture of the compounds I and II and/or III to
V. The active ingredients are employed in a purity of from 90$ to
100, preferably from 95$ to 100$ (according to NMR or HPLC
spectrum.
The compounds I or II and/or III to V, the mixtures, or the
corresponding formulations, are applied by treating the harmful
fungi, their habitat, or the plants, seeds, soils, areas,
materials or spaces to be kept free from them with a fungicidally
effective amount of the mixture, or of the compounds I and II
and/or III to V in the case of separate application.
Application can be effected before or after infection by the
harmful fungi.
Examples of such preparations comprising the active ingredients
are:
I. A solution of 90 parts by weight of the active ingredients
and 10 parts by weight of N-methylpyrrolidone; this
solution is suitable for use in the form of microdrops;
II. A mixture of 20 parts by weight of the active ingredients,
80 parts by weight of xylene, 10 parts by weight of the
adduct of 8 to 10 mol of ethylene oxide to 1 mol of oleic
acid N-monoethanolamide, 5 parts by weight of the calcium
salt of dodecylbenzenesulfonate, 5 parts by weight of the
adduct of 40 mol of ethylene oxide to 1 mol of castor oil;
a dispersion is obtained by finely distributing the
solution in water;
III. An aqueous dispersion of 20 parts by weight of the active
ingredients, 40 parts by weight of cyclohexanone, 30 parts
by weight of isobutanol, 20 parts by weight of the adduct
of 40 mol of ethylene oxide to 1 mol of castor oil;
0050/48655 CA 02571911 2007-O1-10
IV. An aqueous dispersion of 20 parts by weight of the active
ingredients, 25 parts by weight of cyclohexanol, 65 parts
by weight of a mineral oil fraction of boiling point 210 to
280~C, and 10 parts by weight of the adduct of 40 mol of
5 ethylene oxide to 1 mol of castor oil;
V. A mixture, ground in a hammer mill, of 80 parts by weight
of the active ingredients, 3 parts by weight of the sodium
salt of diisobutylnaphthalene-1-sulfonate, 10 parts by
weight of the sodium salt of a lignosulfonic acid from a
10 sulfite waste liquor and 7 parts by weight of pulverulent
silica gel; a spray mixture is obtained by finely
distributing the mixture in water;
VI. An intimate mixture of 3 parts by weight of the active
15 ingredients and 97 parts by weight of finely divided
kaolin; this dust comprises 3% by weight of active
ingredient;
VII. An intimate mixture of 30 parts by weight of the active
ingredients, 92 parts by weight of pulverulent silica gel
20 and 8 parts by weight of paraffin oil which has been
sprayed onto the surface of this silica gel; this
formulation imparts good adhesion to the active ingredient;
VIII. A stable aqueous dispersion of 40 parts by weight of the
active ingredients, 10 parts by weight of the sodium salt
of a phenolsulfonic acid/urea/formaldehyde condensate, 2
parts by weight of silica gel and 48 parts by weight of
water; this dispersion may be diluted further;
IX. A stable oily dispersion of 20 parts by weight of the
active ingredients, 2 parts by weight of the calcium salt
of dodecylbenzenesulfonate, 8 parts by weight of fatty
alcohol polyglycol ether, 20 parts by weight of the sodium
salt of a phenolsulfonic acid/urea/formaldehyde condensate
and 88 parts by weight of a paraffinic mineral oil.
Use Example
The synergistic activity of the mixtures according to the
invention can be demonstrated by the following experiments:
The active ingredients, separately or together, are formulated as
a 10% emulsion in a mixture of 63% by weight of cyclohexanone and
27% by weight of emulsifier, and diluted with water to the
desired concentration.
0050/48655 CA 02571911 2007-O1-10
21
Evaluation is carried out by determining the infected leaf areas
in percent. These percentages are converted into efficacies. The
efficacy (w) is calculated as follows using Abbot's formula:
W = (1 - a)~100/~
a corresponds to the fungal infection of the treated plants in
$ and
~ corresponds to the fungal infection of the untreated
(control) plants in ~
An efficacy of 0 means that the infection level of the treated
plants corresponds to that of the untreated control plants; an
efficacy of 100 means that the treated plants were not infected.
The expected efficacies of the mixtures of the active ingredients
are determined using Colby's formula [R.S. Colby, Weeds 15, 20-22
(1967)] and compared with the observed efficacies.
Colby formula: E = x + y - x~y/100
E expected efficacy, expressed in ~ of the untreated control,
when using the mixture of the active ingredients A and B at
the concentrations a and b
x efficacy, expressed in % of the untreated control, when using
active ingredient A at a concentration a
y efficacy, expressed in % of the untreated control, when using
active ingredient B at a concentration b
Use Example 1 - Activity against Phytophthora infestans on
tomatoes
Leaves of potted plants of the variety "Grolie Fleischtomate" were
sprayed to runoff point with an aqueous suspension which had been
prepared from a stock solution comprising 10~ of active
ingredient, 63$ of cyclohexanone and 27~ of emulsifier. The next
day, the leaves were infected with an aqueous zoospore suspension
of Phytophthora infestans. The plants were subsequently placed in
a chamber saturated with water vapor, at temperatures between 16
and 18~C. After 6 days, the tomato blight on the untreated but
infected control plants had developed to such an extent that the
infection could be determined visually in $.
CA 02571911 2007-O1-10
22
The compounds of the formula I employed were the following
compounds:
CO NH
\ /
I.1 ~ , \
N C1 / ~ v
\
F
CO NH
\ /
I.2 ~ , \
N C1 / ~ v
The results are shown in Tables 1 and 2 below.
Table 1
Concentration of
Efficacy in %
of
Ex. Active ingredient active ingredient the untreated
in the spray control
liquor in ppm
Control
1C 0 (100% infection)0
(untreated)
2C Compound I.1 3.1 0
3C Compound I.2 3.1 0
4C Compound IV.3 3.1 0
Table 2
Mixtures according to the Observed Calculated
Ex. invention (content in ppm) efficacy efficacy
5 *)
3.1 ppm I.1
5 + 20 0
3.1 ppm IV.3
3.1 ppm I.2
6 + 30 0
3.1 ppm IV.3
The test results show that the observed efficacy in all mixing
ratios is higher than the efficacy which had been calculated
beforehand using Colby~s formula.
