U.S. patent application number 09/867524 was filed with the patent office on 2002-02-14 for cycloalkylalkanecarboxamides and their preparation and use.
Invention is credited to Ammermann, Eberhard, Eicken, Karl, Lorenz, Gisela, Rose, Ingo, Strathmann, Siegfried, Wetterich, Frank.
Application Number | 20020019422 09/867524 |
Document ID | / |
Family ID | 7823391 |
Filed Date | 2002-02-14 |
United States Patent
Application |
20020019422 |
Kind Code |
A1 |
Wetterich, Frank ; et
al. |
February 14, 2002 |
Cycloalkylalkanecarboxamides and their preparation and use
Abstract
The present invention relates to novel
cycloalkylalkanecarboxamides of the formula I 1 where the
substituents have the following meanings: A is
C.sub.3-C.sub.6-cycloalkyl; R.sup.1 is C.sub.1-C.sub.6-alkyl or
C.sub.2-C.sub.6-alkenyl; R.sup.2, R.sup.3 and R.sup.4 are hydrogen
or, independently of this meaning, have one of the meanings of the
radical R.sup.1; n is 0 or 1; Y is cyano or halogen; W is phenyl,
naphthyl or heteroaryl.
Inventors: |
Wetterich, Frank;
(Mutterstadt, DE) ; Eicken, Karl; (Wachenheim,
DE) ; Lorenz, Gisela; (Neustadt, DE) ;
Ammermann, Eberhard; (Heppenheim, DE) ; Strathmann,
Siegfried; (Limburgerhof, DE) ; Rose, Ingo;
(Mannheim, DE) |
Correspondence
Address: |
HERBERT B. KEIL
KEIL & WEINKAUF
1101 Connecticut Avenue, N.W.
Washington
DC
20036
US
|
Family ID: |
7823391 |
Appl. No.: |
09/867524 |
Filed: |
May 31, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09867524 |
May 31, 2001 |
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09381050 |
Sep 14, 1999 |
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6265447 |
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Current U.S.
Class: |
514/357 ;
514/428; 514/520; 514/613; 546/329; 546/330; 548/561; 558/392;
564/189; 564/190 |
Current CPC
Class: |
C07C 2601/02 20170501;
A01N 37/34 20130101; C07C 255/31 20130101; C07C 255/58 20130101;
C07C 2601/08 20170501 |
Class at
Publication: |
514/357 ;
546/329; 546/330; 514/428; 514/520; 514/613; 548/561; 558/392;
564/189; 564/190 |
International
Class: |
A61K 031/44; A61K
031/40; A61K 031/277; A61K 031/165 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 14, 1997 |
DE |
19710618.8 |
Claims
We claim:
1. A cycloalkylalkanecarboxamide of the formula I 109where the
substituents have the following meanings: A is
C.sub.3-C.sub.6-cycloalkyl which can have attached to it one to
three substituents selected from the group consisting of halogen
and C.sub.1-C.sub.3-alkyl; R.sup.1 is C.sub.1-C.sub.6-alkyl or
C.sub.2-C.sub.6-alkenyl, it being possible for these radicals to be
partially or fully halogenated and/or to have attached to them one
or two of the following groups: C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio,
C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.3-C.sub.6-cycloalkyl and
phenyl, it being possible for the phenyl to be partially or fully
halogenated and/or have attached to it one to three of the
following radicals: nitro, cyano, C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio,
C.sub.3-C.sub.6-cycloalkyl or heterocyclyl; R.sup.2, R.sup.3 and
R.sup.4 are hydrogen or, independently of this meaning, have one of
the meanings of the radical R.sup.1; n is 0 or 1; Y is cyano or
halogen; W is phenyl, naphthyl or heteroaryl, it being possible for
these radicals to have attached to them one to three of the
following groups: nitro, halogen, cyano, C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio,
C.sub.3-C.sub.6-cycloalkyl and C.sub.1-C.sub.4-alkoxycarbonyl, with
the exception of the compounds of the formula I where n is 0 and A
is cyclopentyl.
2. A cycloalkylalkanecarboxamide of the formula I as claimed in
claim 1 where A is cyclopropyl which can have attached to it one to
three substituents selected from the group consisting of halogen
and C.sub.1-C.sub.3-alkyl.
3. A cycloalkylalkanecarboxamide of the formula I as claimed in
claim 1 where R.sup.1 is methyl and R.sup.2, R.sup.3 and R.sup.4
are hydrogen or methyl.
4. A cycloalkylalkanecarboxamide of the formula I as claimed in
claim 1 where n is 1.
5. A process for the preparation of a cycloalkylalkanecarboxamide
of the formula I as claimed in claim 1, 110which comprises reacting
a carboxylic acid derivative of the formula II 111where the
radicals A, Y, R.sup.3 and R.sup.4 and also n have the meanings
given in claim 1 and X is a nucleophilically exchangeable radical
with an amine of the formula III 112where the radicals Z, R.sup.1
and R.sup.2 have the meanings given in claim 1.
6. A carboxylic acid derivative of the formula IIA 113where X is a
nucleophilically exchangeable radical; A is cyclopropyl which can
have attached to it one to three substituents selected from the
group consisting of halogen and C.sub.1-C.sub.3-alkyl and Y has the
meaning given in claim 1, with the exception of
.alpha.-cyanocyclopropaneacetic acid.
7. A carboxylic acid derivative of the formula IIB 114where X is a
nucleophilically exchangeable radical and the radicals A, R.sup.3,
R.sup.4 and Y have the meanings given in claim 1.
8. A composition comprising such an amount of at least one
cycloalkylalkanecarboxamide of the formula I as claimed in claim 1
that it is effective for controlling harmful fungi and at least one
inert liquid and/or solid carrier and, if appropriate, at least one
surfactant.
9. A method of controlling harmful fungi, which comprises treating
the harmful fungi, their environment or the plants, areas,
materials or spaces to be kept free from them with an effective
amount of a cycloalkylalkanecarboxamide of the formula I as claimed
in claim 1.
10. The use of a cycloalkylalkanecarboxamide of the formula I as
claimed in claim 1 for controlling harmful fungi.
Description
[0001] The present invention relates to novel
cycloalkylalkanecarboxamides of the formula I 2
[0002] where the substituents have the following meanings:
[0003] A is C.sub.3-C.sub.6-cycloalkyl which can have attached to
it one to three substituents selected from the group consisting of
halogen and C.sub.1-C.sub.3-alkyl;
[0004] R.sup.1 is C.sub.1-C.sub.6-alkyl or C.sub.2-C.sub.6-alkenyl,
it being possible for these radicals to be partially or fully
halogenated and/or to have attached to them one or two of the
following groups: C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio,
C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.3-C.sub.6-cycloalkyl and
phenyl, it being possible for the phenyl to be partially or fully
halogenated and/or have attached to it one to three of the
following radicals: nitro, cyano, C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio,
C.sub.3-C.sub.6-cycloalkyl or heterocyclyl;
[0005] R.sup.2, R.sup.3, R.sup.4 are hydrogen or, independently of
this meaning, have one of the meanings of the radical R.sup.1;
[0006] n is 0 or 1;
[0007] Y is cyano or halogen;
[0008] W is phenyl, naphthyl or heteroaryl, it being possible for
these radicals to have attached to them one to three of the
following groups: nitro, halogen, cyano, C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy,
C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.4-alkylthio,
C.sub.3-C.sub.6-cycloalkyl and C.sub.1-C.sub.4-alkoxycarbonyl,
[0009] with the exception of the compounds of the formula I
where
[0010] n is 0 and
[0011] A is cyclopentyl.
[0012] .alpha.-Halo- and .alpha.-cyano-substituted carboxamides
have already been disclosed in the literature for controlling
harmful fungi, in particular for controlling Pyricularia oryzae
(JP-A 57 185202, JP-A 57 188552, JP-A 57 188551, JP-A 58 029751,
JP-A 58 029752, WO 95/31432, JP-A 07 206608, JP-A 07 330511, JP-A
08 012508 and U.S. Pat. No. 4,946,867). J. Pestic. Sci. 12 (1987),
79-84, compiles work relating to the .alpha.-halo-substituted
carboxamides published to date. This publication also attempts to
establish quantitative relationships between structure and effect
for this class of fungicides.
[0013] U.S. Pat. No. 4,946,867 mentions a cyanoacetamide derivative
with a cyclopentyl group in the .alpha.-position,
-N-[1-(4-chlorophenyl)ethyl]-2- -cyano-2-cyclopentylethanamide.
[0014] Since the fungicidal properties of the known compounds are
not always fully satisfactory regarding their activity against
harmful fungi, eg. Pyricularia oryzae, it is an object of the
present invention to find novel carboxamides which are more active
against harmful fungi, eg. Pyricularia oryzae.
[0015] We have found that this object is achieved by the novel
cycloalkylalkanecarboxamides I defined at the outset. Moreover, we
have found processes for the preparation of the compounds I and the
intermediates of the formula II required for their preparation. We
have found compositions which comprise the compounds I, methods of
controlling harmful fungi using the compounds I and finally, the
use of the compounds I for controlling harmful fungi.
[0016] Depending on the substitution pattern, the compounds of the
formula I may contain one or more chiral centers. In this case,
they exist as enantiomer and diastereomer mixtures. The invention
relates to the pure enantiomers and diastereomers and also to
mixtures of these.
[0017] In the definition of the compounds I given at the outset,
collective terms which represent individual enumerations of each of
the group members were used for the radicals R.sup.1 to R.sup.4, A
and Z. The radicals alkyl, alkylthio, alkoxy, alkoxycarbonyl and
alkenyl can be straight-chain or branched.
[0018] The radical cycloalkyl represents the unsubstituted skeleton
if no specific substitution of a hydrogen by halogen or
C.sub.1-C.sub.3-alkyl is mentioned. The radical definition
cyclopentyl, for example, corresponds to the empirical formula
C.sub.5H.sub.10.
[0019] The term "partially or fully halogenated" is intended to
express that in groups characterized thus some or all of the
hydrogen atoms may be replaced by identical or different halogen
atoms. The meaning halogen represents in each case fluorine,
chlorine, bromine or iodine.
[0020] Examples of other meanings are:
[0021] C.sub.1-C.sub.4-alkyl and the alkyl moieties of
C.sub.1-C.sub.4-alkylthio:
[0022] methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl,
2-methylpropyl and 1,1-dimethylethyl;
[0023] C.sub.1-C.sub.6-alkyl:
[0024] C.sub.1-C.sub.4-alkyl as mentioned above, and also pentyl,
1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl,
1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl,
1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl,
1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,
2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl,
1-ethylbutyl, -2-ethylbutyl, 1,1,2-trimethylpropyl,
1-ethyl-1-methylpropyl and 1-ethyl-3-methylpropyl;
[0025] C.sub.1-C.sub.4-haloalkyl:
[0026] a C.sub.1-C.sub.4-alkyl radical as mentioned above which is
partially or fully substituted by fluorine, chlorine, bromine
and/or iodine, eg. chloromethyl, dichloromethyl, trichloromethyl,
fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl,
dichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl,
2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl,
2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl,
2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl,
2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl,
3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl,
2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl,
3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl,
2,2,3,3,3-pentafluoropropyl, heptafluoropropyl,
1-(fluoromethyl)-2-fluoro- ethyl, 1-(chloromethyl)-2-chloroethyl,
1-(bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl,
4-bromobutyl and nonafluorobutyl;
[0027] C.sub.1-C.sub.4-alkoxy and the alkoxy moieties of
C.sub.1-C.sub.4-alkoxycarbonyl:
[0028] methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy,
1-methylpropoxy, 2-methylpropoxy and 1,1-dimethylethoxy;
[0029] C.sub.1-C.sub.4-haloalkoxy: a C.sub.1-C.sub.4-alkoxy radical
as mentioned above which is partially or fully substituted by
fluorine, chlorine, bromine and/or iodine, eg. fluoromethoxy,
difluoromethoxy, trifluoromethoxy, chlorodifluoromethoxy,
bromodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy,
2-bromomethoxy, 2-iodoethoxy, 2,2-difluoroethoxy,
2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy,
2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy,
2,2,2-trichloroethoxy, pentafluoroethoxy, 2-fluoropropoxy,
3-fluoropropoxy, 2-chloropropoxy, 3-chloropropoxy, 2-bromopropoxy,
3-bromopropoxy, 2,2-difluoropropoxy, 2,3-difluoropropoxy,
2,3-dichloropropoxy, 3,3,3-trifluoropropoxy,
3,3,3-trichloropropoxy, 2,2,3,3,3-pentafluoropropoxy,
heptafluoropropoxy, 1-(fluoromethyl)-2-fluo- roethoxy,
1-(chloromethyl)-2-chloroethoxy, 1-(bromomethyl)-2-bromoethoxy,
4-fluorobutoxy, 4-chlorobutoxy, 4-bromobutoxy and
nonafluorobutoxy;
[0030] C.sub.2-C.sub.6-alkenyl: ethylene, prop-1-en-1-yl,
prop-2-en-1-yl, 1-methylethenyl, buten-1-yl, buten-2-yl,
buten-3-yl, 1-methylprop-1-en-1-yl, 2-methylprop-1-en-1-yl,
1-methylprop-2-en-1-yl and 2-methylprop-2-en-1-yl, penten-1-yl,
penten-2-yl, penten-3-yl, penten-4-yl, 1-methylbut-1-en-1-yl,
2-methylbut-1-en-1-yl, 3-methylbut-1-en-1-yl,
1-methylbut-2-en-1-yl, 2-methylbut-2-en-1-yl,
3-methylbut-2-en-1-yl, 1-methylbut-3-en-1-yl,
2-methylbut-3-en-1-yl, 3-methylbut-3-en-1-yl,
1,1-dimethylprop-2-en-1-yl, 1,2-dimethylprop-1-en-1-yl,
1,2-dimethylprop-2-en-1-yl, 1-ethylprop-1-en-2-yl,
1-ethylprop-2-en-1-yl, hex-1-en-1-yl, hex-2-en-1-yl, hex-3-en-1-yl,
hex-4-en-1-yl, hex-5-en-1-yl, 1-methylpent-1-en-1-yl,
2-methylpent-1-en-1-yl, 3-methylpent-1-en-1-yl,
4-methylpent-1-en-1-yl, 1-methylpent-2-en-1-yl,
2-methylpent-2-en-1-yl, 3-methylpent-2-en-1-yl,
4-methylpent-2-en-1-yl, 1-methylpent-3-en-1-yl,
2-methylpent-3-en-1-yl, 3-methylpent-3-en-1-yl,
4-methylpent-3-en-1-yl, 1-methylpent-4-en-1-yl,
2-methylpent-4-en-1-yl, 3-methylpent-4-en-1-yl,
4-methylpent-4-en-1-yl, 1,1-dimethylbut-2-en-1-yl,
1,1-dimethylbut-3-en-1-yl, 1,2-dimethylbut-1-en-1-yl,
1,2-dimethylbut-2-en-1-yl, 1,2-dimethylbut-3-en-1-yl,
1,3-dimethylbut-1-en-1-yl, 1,3-dimethylbut-2-en-1-yl,
1,3-dimethylbut-3-en-1-yl, 2,2-dimethylbut-3-en-1-yl,
2,3-dimethylbut-1-en-1-yl, 2,3-dimethylbut-2-en-1-yl,
2,3-dimethylbut-3-en-1-yl, 3,3-dimethylbut-1-en-1-yl,
3,3-dimethylbut-2-en-1-yl, 1-ethylbut-1-en-1-yl,
1-ethylbut-2-en-1-yl, 1-ethylbut-3-en-1-yl, 2-ethylbut-1-en-1-yl,
2-ethylbut-2-en-1-yl, 2-ethylbut-3-en-1-yl,
1,1,2-trimethylprop-2-en-1-yl, 1-ethyl-1-methyl-prop-2-en-1-yl,
1-ethyl-2-methyl-prop-1-en-1-yl and
1-ethyl-2-methyl-prop-2-en-1-yl;
[0031] C.sub.3-C.sub.6-cycloalkyl: cyclopropyl, cyclobutyl,
cyclopentyl, cyclohexyl;
[0032] heteroaryl: aromatic mono- or polycyclic radicals which,
besides carbon ring members, can additionally contain 1 to 4
nitrogen atoms or 1 to 3 nitrogen atoms and one oxygen or one
sulfur atom or one oxygen or one sulfur atom, eg.:
[0033] 5-membered heteroaryl containing 1 to 3 nitrogen atoms:
[0034] 5-membered heteroaryl ring groups which, in addition to
carbon atoms, may contain 1 to 3 nitrogen atoms as ring members,
eg. 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl,
2-imidazolyl, 4-imidazolyl, 1,2,4-triazol-3-yl and
1,3,4-triazol-2-yl;
[0035] 5-membered heteroaryl containing 1 to 4 nitrogen atoms or 1
to 3 nitrogen atoms and 1 sulfur atom or oxygen atom or 1 oxygen or
1 sulfur atom: 5-membered heteroaryl ring groups which, in addition
to carbon atoms, may contain 1 to 4 nitrogen atoms or 1 to 3
nitrogen atoms and 1 sulfur or oxygen atom or 1 oxygen or sulfur
atom as ring members, eg. 2-furyl, 3-furyl, 2-thienyl, 3-thienyl,
2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl,
3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-pyrazolyl,
4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl,
2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl,
1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,2,4-thiadiazol-3-yl,
1,2,4-thiadiazol-5-yl, 1,2,4-triazol-3-yl, 1,3,4-oxadiazol-2-yl,
1,3,4-thiadiazol-2-yl, 1,3,4-triazol-2-yl;
[0036] benzo-fused 5-membered heteroaryl containing 1 to 3 nitrogen
atoms or 1 nitrogen atom and/or one oxygen or sulfur atom:
5-membered heteroaryl ring groups which, in addition to carbon
atoms, may contain 1 to 4 nitrogen atoms or 1 to 3 nitrogen atoms
and 1 sulfur or oxygen atom or 1 oxygen or one sulfur atom as ring
members and in which 2 adjacent carbon ring members or 1 nitrogen
and 1 adjacent carbon ring member may be bridged by a
buta-1,3-diene-1,4-diyl group;
[0037] 5-membered heteroaryl bonded via nitrogen and containing 1
to 4 nitrogen atoms, or benzo-fused 5-membered heteroaryl bonded
via nitrogen and containing 1 to 3 nitrogen atoms: 5-membered
heteroaryl ring groups which, in addition to carbon atoms, may
contain 1 to 4 nitrogen atoms or 1 to 3 nitrogen atoms,
respectively, as ring members and in which 2 adjacent carbon ring
members or one nitrogen and one adjacent carbon ring member may be
bridged by a buta-1,3-diene-1,4-diyl group, these rings being
bonded to the skeleton via one of the nitrogen ring members;
[0038] 6-membered heteroaryl containing 1 to 3, or 1 to 4, nitrogen
atoms: 6-membered heteroaryl ring groups which, in addition to
carbon atoms, may contain 1 to 3, or 1 to 4, respectively, nitrogen
atoms as ring members, eg. 2-pyridinyl, 3-pyridinyl, 4-pyridinyl,
3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl,
5-pyrimidinyl, 2-pyrazinyl, 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl
and 1,2,4,5-tetrazin-3-yl;
[0039] benzo-fused 6-membered heteroaryl containing 1 to 4 nitrogen
atoms: 6-membered heteroaryl ring groups in which 2 adjacent carbon
ring members may be bridged by a buta-1,3-diene-1,4-diyl group, eg.
quinoline, isoquinoline, quinazoline and quinoxaline.
[0040] Preferred with a view to the fungicidal action against
harmful fungi, eg. Pyricularia oryzae, are
cycloalkylalkanecarboxamides I with the following substituents, the
preference existing in each case alone or in combination:
[0041] The carbon atom which has attached to it the groups R.sup.1
and R.sup.2 is preferably in the R configuration.
[0042] Preferred cycloalkylalkanecarboxamides I are those where
R.sup.1 is methyl and R.sup.2 is either methyl or hydrogen;
especially preferred are compounds I where R.sup.1 is methyl and
R.sup.2 is hydrogen.
[0043] Further preferred cycloalkanecarboxamides [sic] of the
formula I are those where W is unsubstituted or substituted phenyl
which is substituted in particular in the 2-position or in the
positions 2 and 4. Very specially preferred is substitution in the
4-position on the phenyl ring and preferably here substitution by
cyano or methoxy, by preference substitution by methyl and, in
particular, by halogen, chlorine again being preferred here.
[0044] Additionally, preference is given to cycloalkanecarboxamides
of the formula I where W is 1- or 2-naphthyl which is in each case
unsubstituted or substituted by one to three of the following
groups: halogen, cyano, C.sub.1-C.sub.4-alkyl or
C.sub.1-C.sub.4-alkoxy. Particular preference is given to
unsubstituted 1- or 2-naphthyl or 2-naphthyl which carries one of
the following groups: chlorine, cyano, methyl or methoxy.
Unsubstituted 2-naphthyl is particularly preferred.
[0045] Moreover, preferred cycloalkylalkanecarboxamides I are those
where n=1. The substituents R.sup.3 and R.sup.4 are by preference
C.sub.1-C.sub.4-alkyl and in particular methyl or ethyl. Also
preferred is the combination in which one of the two substituents
is hydrogen and the other one is C.sub.1-C.sub.4-alkyl, in
particular methyl or ethyl.
[0046] Furthermore preferred are .alpha.-chloro or
.alpha.-bromocycloalkyl- alkanecarboxamides I (Y=bromine or
chlorine). Especially preferred are
.alpha.-cyanocycloalkylalkanecarboxamides I (Y=cyano).
[0047] Furthermore, preference is given to
cycloalkylalkanecarboxamides of the formula I where A is a
substituted C.sub.3-C.sub.6-cycloalkyl. Particular preference is
given to a methylated C.sub.3-C.sub.6-cycloalkyl radical which
preferably carries the methyl substituent at the carbon linking the
cycloalkane ring with the rest of the molecule.
[0048] Finally, preferred cycloalkylalkanecarboxamides of the
general formula I are those where A is unsubstituted or substituted
cyclopropyl. In particular, cyclopropyl which has attached to it
one to three substituents selected from the group consisting of
chlorine and C.sub.1-C.sub.3-alkyl, in particular methyl, is
preferred. By preference, chlorinated cyclopropyl has attached to
the cyclopropane ring two chlorine atoms in geminal position. By
preference, alkylated or, preferably, methylated, cyclopropyl has
one of the alkyl (methyl) substituents attached to the carbon atom
at the site where the cyclopropane ring is linked to the remaining
moiety.
[0049] Especially preferred with a view to their use are the
compounds compiled in the tables below.
1TABLE 1 Carboxamides Ia.001 to Ia.108 of the formula Ia (* =
configuration of atom designated "*"; R = R configuration; S = S
configuration; rac. = racemic) 3 No. Z.sup.1 Z.sup.2 * Ia.001 H H R
Ia.002 H H S Ia.003 H H rac. Ia.004 H Cl R Ia.005 H Cl S Ia.006 H
Cl rac. Ia.007 H CH.sub.3 R Ia.008 H CH.sub.3 S Ia.009 H CH.sub.3
rac. Ia.010 H OCH.sub.3 R Ia.011 H OCH.sub.3 S Ia.012 H OCH.sub.3
rac. Ia.013 H F R Ia.014 H F S Ia.015 H F rac. Ia.016 H CN R Ia.017
H CN S Ia.018 H CN rac. Ia.019 Cl H R Ia.020 Cl H S Ia.021 Cl H
rac. Ia.022 Cl Cl R Ia.023 Cl Cl S Ia.024 Cl Cl rac. Ia.025 Cl
CH.sub.3 R Ia.026 Cl CH.sub.3 S Ia.027 Cl CH.sub.3 rac. Ia.028 Cl
OCH.sub.3 R Ia.029 Cl OCH.sub.3 S Ia.030 Cl OCH.sub.3 rac. Ia.031
Cl F R Ia.032 Cl F S Ia.033 Cl F rac. Ia.034 Cl CN R Ia.035 Cl CN S
Ia.036 Cl CN rac. Ia.037 CH.sub.3 H R Ia.038 CH.sub.3 H S Ia.039
CH.sub.3 H rac. Ia.040 CH.sub.3 Cl R Ia.041 CH.sub.3 Cl S Ia.042
CH.sub.3 Cl rac. Ia.043 CH.sub.3 CH.sub.3 R Ia.044 CH.sub.3
CH.sub.3 S Ia.045 CH.sub.3 CH.sub.3 rac. Ia.046 CH.sub.3 OCH.sub.3
R Ia.047 CH.sub.3 OCH.sub.3 S Ia.048 CH.sub.3 OCH.sub.3 rac. Ia.049
CH.sub.3 F R Ia.050 CH.sub.3 F S Ia.051 CH.sub.3 F rac. Ia.052
CH.sub.3 CN R Ia.053 CH.sub.3 CN S Ia.054 CH.sub.3 CN rac. Ia.055
OCH.sub.3 H R Ia.056 OCH.sub.3 H S Ia.057 OCH.sub.3 H rac. Ia.058
OCH.sub.3 Cl R Ia.059 OCH.sub.3 Cl S Ia.060 OCH.sub.3 Cl rac.
Ia.061 OCH.sub.3 CH.sub.3 R Ia.062 OCH.sub.3 CH.sub.3 S Ia.063
OCH.sub.3 CH.sub.3 rac. Ia.064 OCH.sub.3 OCH.sub.3 R Ia.065
OCH.sub.3 OCH.sub.3 S Ia.066 OCH.sub.3 OCH.sub.3 rac. Ia.067
OCH.sub.3 F R Ia.068 OCH.sub.3 F S Ia.069 OCH.sub.3 F rac. Ia.070
OCH.sub.3 CN R Ia.071 OCH.sub.3 CN S Ia.072 OCH.sub.3 CN rac.
Ia.073 F H R Ia.074 F H S Ia.075 F H rac. Ia.076 F Cl R Ia.077 F Cl
S Ia.078 F Cl rac. Ia.079 F CH.sub.3 R Ia.080 F CH.sub.3 S Ia.081 F
CH.sub.3 rac. Ia.082 F OCH.sub.3 R Ia.083 F OCH.sub.3 S Ia.084 F
OCH.sub.3 rac. Ia.085 F F R Ia.086 F F S Ia.087 F F rac. Ia.088 F
CN R Ia.089 F CN S Ia.090 F CN rac. Ia.091 CN H R Ia.092 CN H S
Ia.093 CN H rac. Ia.094 CN Cl R Ia.095 CN Cl S Ia.096 CN Cl rac.
Ia.097 CN CH.sub.3 R Ia.098 CN CH.sub.3 S Ia.099 CN CH.sub.3 rac.
Ia.100 CN OCH.sub.3 R Ia.101 CN OCH.sub.3 S Ia.102 CN OCH.sub.3
rac. Ia.103 CN F R Ia.104 CN F S Ia.105 CN F rac. Ia.106 CN CN R
Ia.107 CN CN S Ia.108 CN CN rac.
[0050]
2TABLE 2 Carboxamides Ib.001 to Ib.108 of the formula Ib in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 4
[0051]
3TABLE 3 Carboxamides Ic.001 to Ic.108 of the formula Ic in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 5
[0052]
4TABLE 4 Carboxamides Id.001 to Id.108 of the formula Id in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 6
[0053]
5TABLE 5 Carboxamides Ie.001 to Ie.108 of the formula Ie in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 7
[0054]
6TABLE 6 Carboxamides If.001 to If.108 of the formula If in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 8
[0055]
7TABLE 7 Carboxamides Ig.001 to Ig.108 of the formula Ig in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 9
[0056]
8TABLE 8 Carboxamides Ih.001 to Ih.108 of the formula Ih in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 10
[0057]
9TABLE 9 Carboxamides Ii.001 to Ii.108 of the formula Ii in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 11
[0058]
10TABLE 10 Carboxamides Ik.001 to Ik.108 of the formula Ik in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 12
[0059]
11TABLE 11 Carboxamides Im.001 to Im.108 of the formula Im in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 13
[0060]
12TABLE 12 Carboxamides In.001 to In.108 of the formula In in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 14
[0061]
13TABLE 13 Carboxamides Io.001 to Io.108 of the formula In [sic] in
which the meanings of the combinations of Z.sup.1, Z.sup.2 and "*"
are indicated by the lines of Table 1. 15
[0062]
14TABLE 14 Carboxamides Ip.001 to Ip.108 of the formula Ip in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 16
[0063]
15TABLE 15 Carboxamides Iq.001 to Iq.108 of the formula Iq in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 17
[0064] Moreover, processes have been found with which the
carboxamides I can be prepared in good yields.
16TABLE 16 Carboxamides Ir.001 to Ir.108 of the formula Ir in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 18
[0065]
17TABLE 17 Carboxamides Is.001 to Is.108 of the formula Is in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 19
[0066]
18TABLE 18 Carboxamides It.001 to It.108 of the formula It in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 20
[0067]
19TABLE 19 Carboxamides Iu.001 to Iu.108 of the formula Iu in which
the meanings of the combinations of Z.sup.1, Z.sup.2 and "*" are
indicated by the lines of Table 1. 21
[0068]
20TABLE 20 Carboxamides Iv.1 to Iv.24 of the formula Iv (the
configuration of the atom labeled "*" is racemic) 22 No. A n
R.sup.3 R.sup.4 Y Iv. 1 23 0 -- -- CN Iv. 2 24 0 -- -- CN Iv. 3 25
0 -- -- CN Iv. 4 26 0 -- -- Cl Iv. 5 27 0 -- -- Br Iv. 6 28 0 -- --
CN Iv. 7 29 0 -- -- CN Iv. 8 30 1 H H CN Iv. 9 31 1 CH.sub.3 H CN
Iv. 10 32 1 CH.sub.3 H Br Iv. 11 33 1 CH.sub.3 CH.sub.3 CN Iv. 12
34 1 C.sub.5H.sub.5 H CN Iv. 13 35 1 C.sub.5H.sub.5 CH.sub.3 CN Iv.
14 36 1 C.sub.5H.sub.5 C.sub.5H.sub.5 CN Iv. 15 37 1 H H CN Iv. 16
38 1 CH.sub.3 H CN Iv. 17 39 1 CH.sub.3 CH.sub.3 CN Iv. 18 40 1
C.sub.5H.sub.5 H CN Iv. 19 41 1 CH.sub.3 H CN Iv. 20 42 1 CH.sub.3
CH.sub.3 CN Iv. 21 43 1 C.sub.5H.sub.5 H CN Iv. 22 44 1
C.sub.5H.sub.5 CH.sub.3 CN Iv. 23 45 1 CH.sub.3 H CN Iv. 24 46 1
CH.sub.3 H CN
[0069]
21TABLE 21 Carboxamides Iw.1 to Iw.24 of the formula Iw in which
the meanings of the combinations of A, n, R.sup.3, R.sup.4 and Y
are indicated by the lines of Table 20. (the configuration of the
atom labeled "*" is R) 47
[0070]
22TABLE 22 Carboxamides Iz.1 to Iz.24 of the formula Iz in which
the meanings of the combinations of A, n, R.sup.3, R.sup.4 and Y
are indicated by the lines of Table 20. (the configuration of the
atom labeled "*" is racemic) 48
[0071] According to a process which is preferred in accordance with
the invention, the carboxamides I 49
[0072] are obtained by reacting the carboxylic acid derivatives II
50
[0073] with amines of the formula III 51
[0074] Amide formation is effected by the processes known from the
literature. In the processes, the free carboxylic acid of the
formula II' where X is hydroxyl are, as a rule, previously
converted into an activated carboxylic acid derivative II where X
is, for example, chlorine.
[0075] Activation of the carboxylic acid II' can preferably also be
effected in situ by the direct use of the carboxylic acid II' with
addition of, for example, dicyclohexylcarbodimide, ethyl
chloroformate, diethyl cyanophosphonate,
triphenylphosphine/azodicarboxylic ester, 2-pyridine
disulfide/triphenylphosphine, carbonyldiimidazole, thionyl
chloride, phosphorus trichloride, phosphorus pentachloride, and the
like. In general, the, for example, carbodiimides are added in
equimolar amounts based on the carboxylic acids II'.
[0076] Activation of the carboxylic acids via acyl cyanides is
effected for example for reacting the carboxylic acids II, with
diethyl cyanophosphonate, preferably in an inert solvent such as
tetrahydrofuran, toluene or dichloromethane (cf. Tetrahedron Lett.
18 (1973) 1595-8).
[0077] Activation via anhydrides is effected for example by
reacting the carboxylic acids II' with carbonic acid chlorides,
such as ethyl chloroformate, in general in the presence of bases
and, if appropriate, in an inert solvent such as toluene or
tetrahydrofuran (cf. "Houben-Weyl", 4th ed. (1974), 15/1, page
28-32).
[0078] Amide formation is preferably carried out in the presence of
bases such as tertiary amines, eg. triethylamine or
dimethylcyclohexylamine, alkali metal carbonates, alkali metal
hydroxides, pyridine and the like. The reactants and the auxiliary
base are expediently employed in equimolar amounts. A small excess
of the auxiliary base of from 0.1-0.5 equivalents may be beneficial
under certain circumstances.
[0079] Suitable solvents are aliphatic hydrocarbons such as hexane
and ligroin, aromatic hydrocarbons such as toluene and xylene,
chlorinated hydrocarbons such as methylene chloride and
1,2-dichloroethane, ethers such as methyl tert-butyl ether and
tetrahydrofuran, polar aprotic solvents such as acetonitrile and
dimethylformamide, or esters such as ethyl acetate, or mixtures of
these.
[0080] The molar ratio of carboxylic acid derivatives II to amine
III is generally from 0.8 to 1.5, preferably from 0.9 to 1.1.
[0081] After the reaction is complete, the mixture is worked up as
usual, for example by introducing the reaction mixture into water
followed by extraction of the amide.
[0082] Those amines of the formula III which are not already known
can be obtained readily (cf. Organikum (1993) Barth
Verlagsgesellschaft mbH Leipzig, p. 509 et seq.; "Houben-Weyl",
volume 15/1, pages 648-665; J. Am. Chem. Soc. 58, (1936),
1808-1811, Indian J. Chem. 10 (1972), 366).
[0083] The R isomer can be separated from the racemates of the
amines III 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).
[0084] The preparation of .alpha.-cyanocyclopropylacetic acid is
described in Org. Prep. Proced. Int. 5 (1973), 25-29. Diagram 1
shows a general route for synthesizing carboxylic acids of the
formula II' (cf. Collect. Czech. Chem. Commun. 48 (1983) 1597-1601
and J. Polym. Sci., Polym. Chem. Ed. 14 (1976) 2357-9). 52
[0085] Furthermore, carboxylic acid derivatives of the formula IIA
can be prepared in accordance with Diagram 2. 53
[0086] The cycloalkylacetic acids of the formula IV where A has the
meaning in claim 1 are known (J. Chem. Technol. Biotechnol., Chem.
Technol., 33A (1983) 109-15; NL 65 06 881; Chem. Ber. 41 (1908)
2627; Chem. Ber. 35 (1902) 2688).
[0087] The cycloalkylacetic acids IV can be brominated in the
.alpha. position following the protocol described in J. Am. Chem.
Soc. 70 (1948) 3626-7. Working-up in the presence of a
C.sub.1-C.sub.6-alcohol leads directly to the corresponding ester.
The subsequent bromine/cyano exchange is carried out as described
in Synth. Commun. 23 (1993) 2323-9. Hydrolysis of the esters to the
carboxylic acids IIAA' is carried out by standard methods
(Organikum 1993 Barth Verlagsgesellschaft mbH, Leipzig, p.
431ff.).
[0088] The carboxylic acid derivatives of the formula IIB are
accessible for example via the route shown in Diagram 3. 54
[0089] The starting materials, acyl- or formylcycloalkanes of the
formula V, are generally accessible (cf., inter alia, J. Chem.
Soc., Perkin Trans. I, 6 (1994) 739-52; EP-A 725 066). They are
reacted with C.sub.1-C.sub.6-alkyl .alpha.-halo- or
.alpha.-cyanoacetates in a Knoevenagel reaction to give the Michael
systems VI (cf. Chem. Heterocycl. Compd. 24 (1988) 860-4).
[0090] Condensation is normally effected with a solvent which is
not miscible with water, such as hexane, toluene or xylene, while
removing the water formed during the reaction. To this end, the
reaction mixture is boiled under reflux for several hours.
[0091] The catalysts used are bases, eg. piperidine, pyridine,
ammonia or .beta.-alanine, in the presence of an acid, for example
glacial acetic acid.
[0092] An alkyl Grignard compound of the formula VII where R.sup.3
has the meaning given in claim 1 and Hal is chlorine, bromine or
iodine is subsequently subjected to an addition reaction with a
Michael systems [sic] of the formula VI to obtain saturated systems
of the type IIB.
[0093] The reaction is carried out under solvents which are inert
under reaction conditions. Particularly preferred are ethers such
as tetrahydrofuran, diethyl ether, dimethoxyethane or methyl
tert-butyl ether. As a rule, the reaction temperature is set at
from -10 to 80.degree. C. and preferably from 10 to 60.degree.
C.
[0094] As a rule, the Grignard compound VII is employed in an
equimolar amount based on the Michael system VI. In some cases it
proves advantageous to employ the Grignard compound in an excess of
from 0.2 to 0.5 mol equivalents.
[0095] As a rule, the addition reaction is carried out with copper
catalysts by adding 1-10 mol % of, for example, copper(I) iodide.
This results in a higher selectivity regarding the 1,2-addition
versus the 1,4-addition.
[0096] Finally, the free carboxylic acids IIB' are prepared by
subjecting the corresponding esters to alkaline hydrolysis
(Organikum 1993 Barth Verlagsgesellschaft mbH, Leipzig, p. 431 et
seq.).
[0097] A sophisticated route to obtain
2-cyano-3-(2,2-dichlorocyclopropyl)- -3-methylbutanoic acid is
proposed in Diagram 4. 55
[0098] The preparation of 2-cyano-3,3-dimethylpent-4-enoic acid
from 3-methylbut-2-enyl cyanoacetate is described in DE-A 26 49 711
and Res. Discl. (1985) 249,55.
2-Cyano-3-(2,2-dichlorocyclopropyl)-3-methylbutanoi- c acid can be
obtained directly by an addition reaction with dichlorocarbene,
which is accessible from chloroform and alkali metal hydroxides by
means of standard processes. To improve the yield, it is expedient
to protect the carboxylic acid function before the cyclopropanation
step (for example by converting it into the tert-butyl ester).
[0099] The abovementioned processes allow access to carboxylic acid
derivatives II which are suitable for example for preparing the
carboxamides I according to the invention.
[0100] The specially preferred embodiments of the carboxylic acid
derivatives II with respect to the substituents R.sup.3, R.sup.4, A
and Y correspond to those of the carboxamides I.
[0101] X represents a nucleophilically exchangeable radical such as
hydroxyl, C.sub.1-C.sub.4-alkoxy, halogen eg. bromine or chlorine,
hetaryl, eg. imidazolyl or pyridyl, carboxylate, eg. acetate or
trifluoroacetate, and the like.
[0102] Particularly preferred are carboxylic acid derivatives of
the formula II where n is 1 and/or is unsubstituted or substituted
cyclopropyl. In the event that n is 0, preferred carboxylic acid
derivatives of the formula IIA are those where A is cyclopropyl
which may have attached to it from 1 to 3 substituents, eg.
chlorine and/or C.sub.1-C.sub.3-alkyl. Chlorinated cyclopropyl
preferably has attached to it two chlorine atoms, and these in the
geminal position on the cyclopropane ring.
[0103] The compounds I are distinguished by an outstanding activity
against a broad spectrum of phytopathogenic fungi, in particular
from the classes of the Ascomycetes, Basidiomycetes, Deuteromycetes
and Phycomycetes. Some of them act systemically and they can be
employed in crop protection as foliar- and soil-acting
fungicides.
[0104] They are especially important for controlling a large number
of fungi on a variety of crop plants such as wheat, rye, barley,
oats, rice, maize, grass, bananas, cotton, soybeans, coffee, sugar
cane, grapevines, fruit species, ornamentals and vegetables such as
cucumbers, beans, tomatoes, potatoes and cucurbits, and on the
seeds of these plants.
[0105] Specifically, they are suitable for controlling the
following plant diseases: Erysiphe graminis (powdery mildew) in
cereals, Erysiphe cichoracearum and Sphaerotheca fuliginea on
cucurbits, Podosphaera leucotricha on apples, Uncinula necator on
grapevines, Puccinia species on cereals, Rhizoctonia species on
cotton, rice and lawns, Ustilago species on cereals and sugar cane,
Venturia inaequalis (scab) on apples, Helminthosporium species on
cereals, Septoria nodorum on wheat, Botrytis cinerea (gray mold) on
strawberries, ornamentals, vegetables and grapevines, Cercospora
arachidicola on groundnuts, Pseudocercosporella herpotrichoides on
wheat, barley, Pyricularia oryzae on rice, Phytophthora infestans
on potatoes and tomatoes, Fusarium and Verticillium species on a
variety of plants, Plasmopara viticola on grapevines,
Pseudoperonospera [sic] species in hops and cucumbers, Alternaria
species on vegetables and fruit, and Mycosphaerella species in
bananas.
[0106] Moreover, the compounds I are suitable for controlling
harmful fungi in the protection of materials (eg. wood, paper,
dispersions for paint, fibers or fabrics) and in the protection of
stored products.
[0107] The compounds I are applied by treating the fungi or the
plants, seeds, materials or the soil to be protected against fungal
infection with a fungicidally reactive amount of the active
ingredients. Application is effected before or after infection of
the materials, plants or seeds by the fungi.
[0108] They can be converted into customary formulations, such as
solutions, emulsions, suspensions, dusts, powders, pastes and
granules. The use form depends on the intended purpose; in any
case, it should guarantee fine and uniform distribution of the
compound 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 also being possible to use other organic solvents
as auxiliary solvents if water is used as the diluent. Auxiliaries
are essentially: solvents such as aromatics (eg. xylene),
chlorinated aromatics (eg. chlorobenzenes), paraffins (eg.
petroleum 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. highly
disperse silica, silicates); emulsifiers, such as non-ionic and
anionic emulsifiers (eg. polyoxyethylene fatty alcohol ethers,
alkylsulfonates and arylsulfonates) and dispersants such as
lignin-sulfite waste liquors and methylcellulose.
[0109] In general, the fungicidal compositions comprise from 0.1 to
95% by weight, preferably from 0.5 to 90% by weight of active
ingredient.
[0110] Depending on the nature of the desired effect, the
application rates are from 0.01 to 2.0 kg of active ingredient per
ha when used in crop protection.
[0111] In the treatment of seeds, amounts of from 0.001 to 0.1 g,
preferably from 0.01 to 0.05 g, of active ingredient are generally
required per kilogram of seed.
[0112] When used in the protection of materials or stored products,
the rate of application of the active ingredient depends on the
nature of the field of application and of the desired effect. For
example, normal rates of application in the protection of materials
are from 0.001 g to 2 kg, preferably 0.005 g to 1 kg, of active
ingredient per cubic meter of treated material.
[0113] In their use form as fungicides, the compositions according
to the invention can also be present together with other active
ingredients, eg. with herbicides, insecticides, growth regulators,
fungicides or else with fertilizers.
[0114] A mixture with fungicides frequently results in a widened
fungicidal spectrum of action.
[0115] The following list of fungicides together with which the
compounds according to the invention can be used is intended to
illustrate the possible combinations, but not to impose any
limitation:
[0116] sulfur, dithiocarbamates and their derivatives, such as
iron(III) dimethyldithiocarbamate, zinc dimethyldithiocarbamate,
zinc ethylenebisdithiocarbamate, manganese
ethylenebisdithiocarbamate, manganese zinc
ethylenediaminebisdithiocarbamate, tetramethylthiuram disulfides
[sic], ammonia complex of zinc [N,N-ethylenebisdithiocarbamate- ],
ammonia complex of zinc [N,N'-propylenebisdithiocarbamate], zinc
[N,N'-propylenebisdithiocarbamate],
N,N'-polypropylenebis(thiocarbamoyl) disulfide;
[0117] nitro derivatives, such as dinitro(1-methylheptyl)phenyl
crotonate, 2-sec-butyl-4,6-dinitrophenyl 3,3-dimethylacrylate,
2-sec-butyl-4,6-dinitrophenyl isopropyl carbonate, diisopropyl
5-nitroisophthalate;
[0118] heterocyclic substances, such as 2-heptadecyl-2-imidazoline
acetate, 2,4-dichloro-6-(o-chloroanilino)-s-triazine, O,O-diethyl
phthalimidophosphonothioate,
5-amino-1-[bis(dimethylamino)phosphinyl]-3-p- henyl-1,2,4-triazole,
2,3-dicyano-1,4-dithioanthraquinone,
2-thio-1,3-dithiolo[4,5-b]quinoxaline, methyl
1-(butylcarbamoyl)-2-benzim- idazolecarbamate,
2-methoxycarbonylaminobenzimidazole, 2-(2-furyl)benzimidazole,
2-(4-thiazolyl)benzimidazole,
N-(1,1,2,2-tetrachloroethylthio)tetrahydrophthalimide,
N-trichloromethylthiotetrahydrophthalimide,
N-trichloromethylthiophthalim- ide,
[0119] N-dichlorofluoromethylthio-N',N'-dimethyl-N-phenylsulfamide,
5-ethoxy-3-trichloromethyl-1,2,3-thiadiazole,
2-thiocyanatomethylthiobenz- othiazole,
1,4-dichloro-2,5-dimethoxybenzene, 4-(2-chlorophenylhydrazono)--
3-methyl-5-isoxazolone, pyridine-2-thiol 1-oxide,
8-hydroxyquinoline or its copper salt,
2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiine,
2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiine 4,4-dioxide,
2-methyl-5,6-dihydro-4H-pyran-3-carboxanilide,
2-methylfuran-3-carboxanil- ide, 2,5-dimethylfuran-3-carboxanilide,
2,4,5-trimethylfuran-3-carboxanili- de,
N-cyclohexyl-2,5-dimethylfuran-3-carboxamide,
N-cyclohexyl-N-methoxy-2- ,5-dimethylfuran-3-carboxamide,
2-methylbenzanilide, 2-iodobenzanilide, N-formyl-N-morpholine
2,2,2-trichloroethyl acetal,
piperazine-1,4-diylbis(2,2,2-trichloroethyl)formamide,
1-(3,4-dichloroanilino)-1-formylamino-2,2,2-trichloroethane,
2,6-dimethyl-N-tridecylmorpholine or its salts,
2,6-dimethyl-N-cyclododec- ylmorpholine or its salts,
N-[3-(p-tert-butylphenyl)-2-methylpropyl]-cis-2-
,6-dimethylmorpholine,
N-[3-(p-tert-butylphenyl)-2-methylpropyl]piperidine- ,
1-[2-(2,4-dichlorophenyl)-4-ethyl-1,3-dioxolan-2-ylethyl]-1H-1,2,4-triaz-
ole,
1-[2-(2,4-dichlorophenyl)-4-n-propyl-1,3-dioxolan-2-ylethyl]-1H-1,2,4-
-triazole,
N-(n-propyl)-N-(2,4,6-trichlorophenoxyethyl)-N'-imidazolylurea,
1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone,
1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-2-butanol,
(2RS,3RS)-1-[3-(2-chlorophenyl)-2-(4-fluorophenyl)oxiran-2-ylmethyl]-1H-1-
,2,4-triazole,
.alpha.-(2-chlorophenyl)-.alpha.-(4-chlorophenyl)-5-pyrimid-
inemethanol, 5-butyl-2-dimethylamino-4-hydroxy-6-methylpyrimidine,
bis(p-chlorophenyl)-3-pyridinemethanol,
1,2-bis(3-ethoxycarbonyl-2-thiour- eido)benzene,
1,2-bis(3-methoxycarbonyl-2-thioureido)benzene,
[0120] strobilurins such as methyl
E-methoximino-[.alpha.-(o-tolyloxy)-o-t- olyl]acetate, methyl
E-2-{2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-
-methoxyacrylate,
N-methyl-E-methoximino-[.alpha.-(2-phenoxyphenyl)]acetam- ide,
N-methyl-E-methoximino-[.alpha.-(2,5-dimethylphenoxy)-o-tolyl]acetami-
de,
[0121] anilinopyrimidines such as
N-(4,6-dimethylpyrimidin-2-yl)aniline,
N-(4-methyl-6-(1-propynyl)pyrimidin-2-yl]aniline,
N-(4-methyl-6-cycloprop- ylpyrimidin-2-yl)aniline,
[0122] phenylpyrroles such as
4-(2,2-difluoro-1,3-benzodioxol-4-yl)-pyrrol- e-3-carbonitrile,
[0123] cinnamamides such as
3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)acry- loylmorpholine,
[0124] and a variety of fungicides, such as dodecylguanidine
acetate,
3-[3-(3,5-dimethyl-2-oxycyclohexyl)-2-hydroxyethyl]glutarimide,
hexachlorobenzene, methyl
N-(2,6-dimethylphenyl)-N-(2-furoyl)-DL-alaninat- e,
DL-N-(2,6-dimethylphenyl)-N-(2'-methoxyacetyl)alanine methyl ester,
N-(2,6-dimethylphenyl)-N-chloroacetyl-D,L-2-aminobutyrolactone,
DL-N-(2,6-dimethylphenyl)-N-(phenylacetyl)alanine methyl ester,
5-methyl-5-vinyl-3-(3,5-dichlorophenyl)-2,4-dioxo-1,3-oxazolidine,
3-[3,5-dichlorophenyl(-5-methyl-5-methoxymethyl]-1,3-oxazolidine-2,4-dion-
e, 3-(3,5-dichlorophenyl)-1-isopropylcarbamoylhydantoin,
N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximide,
2-cyano-[N-(ethylaminocarbonyl)-2-methoximino]acetamide,
1-[2-(2,4-dichlorophenyl)pentyl]-1H-1,2,4-triazole,
2,4-difluoro-.alpha.-(1H-1,2,4-triazolyl-1-methyl)benzhydryl
alcohol,
N-(3-chloro-2,6-dinitro-4-trifluoromethylphenyl)-5-trifluoromethyl-3-chlo-
ro-2-aminopyridine,
1-((bis(4-fluorophenyl)methylsilyl)methyl)-1H-1,2,4-tr- iazole.
[0125] The active ingredients can be applied as such in the form of
their formulations or in the form of the use forms prepared
therefrom, eg. in the form of directly sprayable solutions,
powders, suspensions or dispersions, emulsions, oil dispersions,
pastes, dusts, materials for spreading, or granules, by means of
spraying, atomizing, dusting, spreading or pouring. The use forms
depend entirely on the intended purposes; in any case, they should
guarantee the finest possible distribution of the active
ingredients according to the invention.
[0126] The active ingredient concentrations in the ready-to-use
preparations can be varied within substantial ranges.
[0127] They are in general from 0.0001 to 10%, preferably from 0.01
to 1%.
[0128] The active ingredients can also be used successfully in the
ultra-low-volume method (ULV), it being possible to apply
formulations with over 95% by weight of active ingredient, or even
the active ingredient without additives.
[0129] The rate of application of active ingredient for controlling
pests is from 0.1 to 2.0, preferably from 0.2 to 1.0, kg/ha under
field conditions.
[0130] Substances which are suitable for the preparation of
directly sprayable solutions, emulsions, pastes or oil dispersions
are mineral oil fractions of medium to high boiling point, such as
kerosene or diesel oil, furthermore coal tar oils and oils of
vegetable and animal origin, aliphatic, cycloaliphatic and aromatic
hydrocarbons, eg. benzene, toluene, xylene, paraffin,
tetrahydronaphthalene, alkylated naphthalenes or their derivatives,
methanol, ethanol, propanol, butanol, chloroform, carbon
tetrachloride, cyclohexanol, cyclohexanone, chlorobenzene,
isophorone, strongly polar solvents, eg. dimethylformamide,
dimethyl sulfoxide, N-methylpyrrolidone or water.
[0131] Aqueous use forms can be prepared from emulsion
concentrates, pastes or wettable powders (sprayable powders, oil
dispersions) by adding water. To prepare emulsions, pastes or oil
dispersions, the substances, as such or dissolved in an oil or
solvent, can be homogenized in water by means of wetting agent,
tackifier, dispersant or emulsifier. However, it is also possible
to prepare concentrates composed of active ingredient, wetting
agent, tackifier, dispersant or emulsifier and, if desired, solvent
or oil, and these concentrates are suitable for dilution with
water. Suitable surfactants are alkali metal salts, alkaline earth
metal salts and ammonium salts of lignosulfonic acid,
naphthalenesulfonic acid, phenolsulfonic acid,
dibutylnaphthalenesulfonic acid; alkylarylsulfonates, alkyl
sulfates, alkylsulfonates, fatty alcohol sulfates and fatty acids
and their alkali metal and alkaline earth metal salts, salts of
sulfated fatty alcohol glycol ether, condensates of sulfonated
naphthalene and naphthalene derivatives with formaldehyde,
condensates of naphthalene or of naphthalenesulfonic acid with
phenol and formaldehyde, polyoxyethylene octylphenyl ether,
ethoxylated isooctylphenol, octylphenol, nonylphenol, alkylphenyl
polyglycol ethers, tributylphenyl polyglycol ether, alkylaryl
polyether alcohols, isotridecyl alcohol, fatty alcohol/ethylene
oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl
ether, ethoxylated polyoxypropylene, lauryl alcohol polyglycol
ether acetal, sorbitol esters, lignin-sulfite waste liquors and
methylcellulose.
[0132] Powders, materials for spreading and dusts can be prepared
by mixing or concomitantly grinding the active ingredients with a
solid carrier.
[0133] In general, the formulations comprise from 0.01 to 95% by
weight, preferably from 0.1 to 90% by weight, of the active
ingredients. The active ingredients are employed in a purity of
from 90% to 100%, preferably 95% to 100% (according to NMR
spectrum).
[0134] Examples of formulations are:
[0135] I. 5 parts by weight of a compound according to the
invention mixed intimately with 95 parts by weight of finely
divided kaolin. This gives a dust which comprises 5% by weight of
the active ingredient.
[0136] II. 30 parts by weight of a compound according to the
invention are mixed intimately with a mixture of 92 parts by weight
of pulverulent silica gel and 8 parts by weight of paraffin oil
which had been sprayed onto the surface of this silica gel. This
gives a formulation of the active ingredient with good adhesive
properties (active ingredient content 23% by weight).
[0137] III. 10 parts by weight of a compound according to the
invention are dissolved in a mixture which is composed of 90 parts
by weight of xylene, 6 parts by weight of the adduct of 8 to 10 mol
of ethylene oxide and 1 mol of oleic acid N-monoethanolamide, 2
parts by weight of calcium dodecylbenzene sulfonate and 2 parts by
weight of the adduct of 40 mol of ethylene oxide and 1 mol of
castor oil (active ingredient content 9% by weight).
[0138] IV. 20 parts by weight of a compound according to the
invention are dissolved in a mixture composed of 60 parts by weight
of cyclohexanone, 30 parts by weight of isobutanol, 5 parts by
weight of the adduct of 7 mol of ethylene oxide and 1 mol of
isooctylphenol and 5 parts by weight of the adduct of 40 mol of
ethylene oxide and 1 mol of castor oil (active ingredient content
16% by weight).
[0139] V. 80 parts by weight of a compound according to the
invention are mixed thoroughly with 3 parts by weight of sodium
diisobutylnaphthalene-a- lpha-sulfonamide, 10 parts by weight of
the sodium salt of a lignosulfonic acid from a sulfite waste liquor
and 7 parts by weight of pulverulent silica gel, and the mixture is
ground in a hammer mill (active ingredient content 80% by
weight).
[0140] VI. 90 parts by weight of a compound according to the
invention are mixed with 10 parts by weight of
N-methyl-.alpha.-pyrrolidone; this gives a solution which is
suitable for use in the form of microdrops (active ingredient
content 90% by weight).
[0141] VII. 20 parts by weight of a compound according to the
invention are dissolved in a mixture composed of 40 parts by weight
of cyclohexanone, 30 parts by weight of isobutanol, 20 parts by
weight of the adduct of 7 mol of ethylene oxide and 1 mol of
isooctylphenol and 10 parts by weight of the adduct of 40 mol of
ethylene oxide and 1 mol of castor oil. Pouring the solution into
100,000 parts by weight of water and distributing it therein gives
an aqueous dispersion which comprises 0.02% by weight of the active
ingredient.
[0142] VIII. 20 parts by weight of a compound according to the
invention are mixed thoroughly with 3 parts by weight of sodium
diisobutylnaphthalene-.alpha.-sulfonate, 17 parts by weight of the
sodium salt of a lignosulfonic acid from a sulfite waste liquor and
60 parts by weight of pulverulent silica gel, and the mixture is
ground in a hammer mill. Finely distributing the mixture in 20,000
parts by weight of water gives a spray mixture which comprises 0.1%
by weight of the active ingredient.
[0143] Granules, eg. coated granules, impregnated granules and
homogeneous granules, can be prepared by binding the active
ingredient to solid carriers. Examples of solid carriers are
mineral earths, such as silica gel [sic], silicas, silica gels,
silicates, talc, kaolin, attaclay, limestone, lime, chalk, bole,
loess, clay, dolomite, diatomaceous earth, calcium sulfate,
magnesium sulfate, magnesium oxide, ground synthetic materials,
fertilizers, eg. ammonium sulfate, ammonium phosphate, ammonium
nitrate, ureas and products of vegetable origin such as cereal
meal, tree bark meal, wood meal and nutshell meal, cellulose
,powders and other solid carriers.
[0144] Various types of oils, or herbicides, fungicides, other
pesticides, or bactericides may be added to the active ingredients,
if appropriate also only just prior to use (tank mix). These agents
can be admixed with compositions according to the invention in a
weight ratio of 1:10 to 10:1.
SYNTHESIS EXAMPLES
[0145] Preparation of the Carboxylic Acid Derivatives II
Example 1
[0146] 1-Cyano-1-(2,2-dichloro-1-methylcyclopropyl)acetic Acid
(comp. II.1 in Table A)
[0147] a) Ethyl
1-bromo-1-(2,2-dichloro-1-methylcyclopropyl)acetate
[0148] 1-(2,2-Dichloro-1-methylcyclopropyl)acetic acid (cf. in this
context J. Chem. Technol. Biotechnol. Chem. Technol. Vol. 33A,
(1983), 109-15) was reacted in a accordance with the protocol in J.
Am. Chem. Soc. 70, (1948), pages 3626-7, to give ethyl
1-bromo-1-(2,2-dichloro-1-me- thylcyclopropyl)acetate.
[0149] b) Ethyl
1-cyano-1-(2,2-dichloro-1-methylcyclopropyl)acetate
[0150] Bromine was exchanged for cyano by a protocol similar to
Synth. Commun. 23, (1993), pages 2323-9.
[0151] c) 1-Cyano-1-(2,2-dichloro-1-methylcyclopropyl)acetic
Acid
[0152] The ester was hydrolyzed by refluxing ethyl
1-cyano-1-(2,2-dichloro- -1-methylcyclopropyl)acetate for 4 hours
in a mixture of equal parts of methanol, tetrahydrofuran and 2 N
sodium hydroxide solution. For working-up, the same volume of 2 N
sodium hydroxide solution was added, and the mixture was repeatedly
extracted with diethyl ether. The aqueous phase was subsequently
acidified by adding hydrochloric acid and also extracted with
ether. Drying and concentrating this organic phase gave the title
compound.
Example 2
[0153] 1-Cyano-1-(2,2-dichlorocyclopropyl)acetic Acid (Comp. II.2
in Table A)
[0154] a) Ethyl 1-bromo-1-(2,2-dichlorocyclopropyl)acetate
[0155] 1-(2,2-Dichlorocyclopropyl)acetic acid (cf., in this
context, NL 6506881) was reacted in accordance with the protocol in
J. Am. Chem. Soc. Vol. 70, (1948), pages 3626-7 to give ethyl
1-bromo-1-(2,2-dichlorocyclop- ropyl)acetate.
[0156] b) Ethyl 1-cyano-1-(2,2-dichlorocyclopropyl)acetate
[0157] Bromine was exchanged for cyano by a protocol similar to
Synth. Commun. 23, (1993), pages 2323-9.
[0158] c) 1-Cyano-1-(2,2-dichlorocyclopropyl)acetic Acid
[0159] The ester was hydrolyzed by a method similar to Example
1c).
Example 3
[0160] 2-Cyano-3-cyclopropylbutanoic Acid (comp. II.3 in Table
A)
[0161] a) Ethyl 2-cyano-3-cyclopropyl-2-propenoate
[0162] A solution of 14 g (0.2 mol) of cyclopropylcarbaldehyde,
22.6 g (0.2 mol) of ethyl cyanoacetate, 1.4 ml of glacial acetic
acid and 0.4 ml of piperidine in 200 ml of toluene was refluxed for
6 hours. After cooling, the mixture was washed with in each case
300 ml of 10% strength hydrochloric acid and water. The organic
phase was dried and concentrated and the residue was subjected to
distillation in vacuo. This gave 14.2 g (yield 43%) of ethyl
2-cyano-3-cyclopropyl-2-propenoate (b.p. 95.degree. C./0.3
mbar).
[0163] b) Ethyl 2-cyano-3-cyclopropylbutanoate
[0164] 7.3 g (44 mmol) of ethyl 2-cyano-3-cyclopropyl-2-propenoate
and 0.15 g of copper (I) iodide were introduced into 100 ml of dry
diethyl ether. 16.9 ml of etheric 3 M methylmagnesium bromide
solution (51 mmol) was then added dropwise at reflux temperature,
and the mixture was subsequently stirred for 14 hours at room
temperature. For working-up, the mixture was poured into 300 ml of
ice-water and stirred for 10 minutes. The aqueous phase was
separated off and washed with ether. The combined organic phase
[sic] were washed with saturated sodium chloride solution, dried
with sodium sulfate and concentrated. The residue was subjected to
fractional distillation in vacuo. This gave 4.9 g (yield 61%) of
ethyl 2-cyano-3-cyclopropylbutanoate (b.p. 90.degree. C./2
mbar).
[0165] c) 2-Cyano-3-cyclopropyl-butanoic Acid
[0166] 39.8 g (0.22 mol) of ethyl 2-cyano-3-cyclopropylbutanoic
acid were refluxed for 4 hours in a mixture of in each case 150 ml
of methanol, tetrahydrofuran and 2 N sodium hydroxide solution. For
working-up, 200 ml of 2 N sodium hydroxide solution were added and
the mixture was extracted repeatedly with diethyl ether. The
aqueous phase was subsequently acidified by adding hydrochloric
acid and also extracted with ether. After this organic phase had
been dried and concentrated, 29 g (yield 86%) of
2-cyano-3-cyclopropylbutanoic acid were obtained.
Example 4
[0167] 2-Cyano-3-cyclopropyl-3-methylbutanoic Acid (Comp. II.4 in
Table A)
[0168] a) Ethyl 2-cyano-3-cyclopropylbut-2-enoate
[0169] A solution of 118 g (1.4 mol) of cyclopropyl methyl ketone
and 113 g (1 mol) of ethyl cyanoacetate was reacted by a method
similar to Example 3a) to give 50 g (yield 29%) of ethyl
2-cyano-3-cyclopropylbut-2-- enoate (b.p. 105.degree. C./6
mbar).
[0170] b) Ethyl 2-Cyano-3-cyclopropyl-3-methylbutanoate
[0171] 50 g (0.28 mol) of ethyl
2-cyano-3-cyclopropyl-3-methylprop-2-enoat- e and 1.7 g of copper
(I) iodide were reacted by a method similar to Example 3b) to give
20 g (yield 37%) of ethyl 2-cyano-3-cyclopropyl-3-met- hylbutanoate
(b.p. 120.degree. C./6 mbar).
[0172] c) 2-Cyano-3-cyclopropyl-3-methylbutanoic Acid
[0173] 20 g (0.1 mol) of ethyl
2-cyano-3-cyclopropyl-3-methylbutanoate were hydrolyzed by a method
similar to Example 3c). This gave 13 g (yield 76%) of
2-cyano-3-cyclopropyl-3-methylbutanoic acid.
Example 5
[0174] 2-Cyano-3-(2,2-dichloro-1-methylcyclopropyl)butanoic Acid
(Comp. II.5 in Table A)
[0175] a) Ethyl
2-cyano-3-(2,2-dichloro-1-methylcyclopropyl)prop-2-enoate
[0176] 65.8 g (0.43 mol) of
(2,2-dichloro-1-methylcylopropyl)carbaldehyde (cf., in this
context, J. Chem. Soc., Perkin Trans. I, (1994), Vol. 6, pages
739-52) and 48.6 g (0.43 mol) of ethyl cyanoacetate were reacted by
a method similar to Example 3a) and gave, after distillation, 63 g
(yield 60%) of a pale yellow oil.
[0177] B.p. 95.degree. C./0.8 mbar, .sup.1H NMR (in CDCl.sub.3):
1.4 (t, 3H); 1.64 (s, 3H); 1.8 (d, 1H); 2.04 (d, 1H); 4.3 (q, 2H);
7.8 (s, 1H)).
[0178] b) Ethyl
2-cyano-3-(2,2-dichloro-1-methylcyclopropyl)butanoate
[0179] 5 g (20 mmol) of the ester obtained in Example 5a) were
reacted by a method similar to Example 3b) to give 5 g (yield 95%)
of ethyl 2-cyano-3-(2,2-dichloro-1-methylcyclopropyl)butanoate.
[0180] B.p. 110.degree. C./0.5 mbar.
[0181] c) 2-Cyano-3-(2,2-dichloro-1-methylcyclopropyl)butanoic
Acid
[0182] 2 g (7.6 mmol) of the ester obtained in Example 5b) were
hydrolyzed by a method similar to Example 3c) to give 1.7 g (yield
95%) of the acid as a brown oil.
Example 6
[0183] 2-Cyano-3-(2,2-dichloroyclopropyl)-3-methyl-butanoic Acid
(Comp. II.6 in Table A)
[0184] 2-Cyano-3,3-dimethylpent-4-enoic acid (cf., in this context,
DE 2649711 and Res. Discl. (1985), 249, 55.) was cyclopropanized in
accordance with the protocol in J. Chem. Technol. Biotechnol.,
Chem. Technol. (1983), Vol. 33A, 109-15.
Example 7
[0185] 2-Cyano-3-(2,2-dichlorocyclopropyl)propionic Acid (comp.
II.7 in Table A)
[0186] a) Ethyl 2-cyano-3-(2,2-dichlorocyclopropyl)propionate
[0187] 4.5 g (39 mmol) of ethyl cyanoacetate and 9.6 g (47 mmol) of
1-bromo-1-(2,2-dichlorocyclopropyl)methane were initially charged
under nitrogen in 26 ml of absolute ethanol. With stirring, 7.0 g
of a 30% strength methanolic sodium methoxide solution were then
added dropwise. The mixture was heated under reflux for 2 hours.
After cooling to room temperature, the mixture was stirred
overnight. The methanol was evaporated and the precipitated NaBr
was completely dissolved by addition of water, with cooling to
10.degree. C. The aqueous phase was extracted three times using
methyl tert-butyl ether and the combined organic phases were then
washed twice with water. The organic phase was dried using sodium
sulfate, the solvent was removed and the crude product obtained as
a residue was subjected to fractional distillation. This gave 2.4 g
(26% yield) of ethyl
2-cyano-3-(2,2-dichlorocyclopropyl)propionate.
[0188] b) 2-Cyano-3-(2,2-dichlorocyclopropyl)propionic Acid
[0189] The hydrolysis of the ester was carried out similarly to
Example 1c).
Example 8
[0190] (1-Methylcyclopentyl)cyanoacetic Acid (Compound II.8 in
Table A)
[0191] a) Methyl cyanocyclopentylidineacetate
[0192] Similarly to Example 3a), a solution of 235 g (2.8 mol) of
cyclopentanone and 198 g (2 mol) of methyl cyanoacetate was reacted
to give 297 g (90% yield) of methyl cyanocyclopentylidine acetate.
bp. 92.degree. C./0.8 mbar.
[0193] b) Methyl (1-methylcyclopentyl)cyanoacetate
[0194] Similarly to Example 3b), 100 g (0.61 mol) of methyl
cyanocyclopentylidineacetate and 0.7 g of. copper (I) iodide were
reacted to give 48 g (44% yield) of methyl
(1-methylcyclopentyl)cyanoacetate. bp. 85.degree. C./1.1 mbar.
[0195] c) (1-Methylcyclopentyl)cyanoacetic Acid
[0196] Similarly to Example 3c), 48 g (0.26 mol) of methyl
(1-methylcyclopentyl)cyanoacetate were hydrolyzed. This gave 44 g
(100% yield) of (1-methylcyclopentyl)cyanoacetic acid.
Example 9
[0197] 2-Cyano-3-cyclopropylpentanoic Acid (comp. II.9 in Table
A)
[0198] a) Methyl 2-cyano-3-cyclopropylpent-2-enoate
[0199] Similarly to Example 3a), a solution of 4 g (40.8 mmol) of
cyclopropyl ethyl ketone and 2.4 g (24 mmol) of methyl cyanoacetate
was reacted to give 0.9 g (21% yield) of methyl
2-cyano-3-cyclopropylpent-2-e- noate.
[0200] b) 2-Cyano-3-cyclopropylpentanoate
[0201] Under an atmosphere of nitrogen, 1 g (5.6 mmol) of the ester
9a) was initially charged in 10 ml of tetrahydrofuran and 5 ml of
abs. methanol. After the addition of 0.3 g (5.6 mmol) of potassium
borohydride, the mixture was stirred at room temperature overnight.
For work-up, the mixture was hydrolyzed with water and acidified
with 2N hydrochloric acid, and the aqueous phase was extracted with
methyl tert-butyl ether. The combined organic phases were washed
with water and saturated sodium chloride solution. The organic
phases were dried using sodium sulfate and the solvent was removed,
giving 0.6 g (60% yield) of methyl
2-cyano-3-cyclopropylpentanoate.
[0202] c) 2-Cyano-3-cyclopropylpentanoic Acid
[0203] Similarly to Example 1c), 0.6 g of the ester 9b) was
hydrolyzed. This gave 0.54 g (98% yield) of the title is
compound.
Example 10
[0204] 2-Cyano-3-cyclopropyl-3-methylpentanoic Acid (comp. II.10 in
Table A)
[0205] a) Methyl 2-cyano-3-cyclopropyl-3-methylpentanoate
[0206] Similarly to Example 3b), 1 g (5.6 mmol) of the ester 9a)
was reacted. This gave 1.1 g of crude product which was used
without any further purification.
[0207] b) 2-Cyano-3-cyclopropyl-3-methylpentanoic Acid
[0208] Similarly to Example 1c), 0.5 g (2.56 mmol) of the ester
10a) was hydrolyzed. This gave 0.44 g (96% yield) of the title
compound.
23TABLE A 56 Physical data (NMR in CDCl.sub.3, No. A n R.sup.3
R.sup.4 Y data in ppm; m.p. in .degree. C.) II. 1 57 0 -- -- CN II.
2 58 0 -- -- CN II. 3 59 1 CH.sub.3 H CN .sup.13C NMR: 5; 14.6; 16;
40; 44; 67; 115; 170 II. 4 60 1 CH.sub.3 CH.sub.3 CN .sup.1H NMR:
0.3-0.6; 1.0; 3.4; 8.7 II. 5 61 1 CH.sub.3 H CN .sup.13C NMR: 15;
33; 41; 67; 115; 170 II. 6 62 1 CH.sub.3 CH.sub.3 CN II. 7 63 1 H H
CN .sup.1H NMR: 1.3; 1.8; 2.1-2.5; 3.8; 7.8 II. 8 64 0 -- -- CN
.sup.1H NMR: 1.2; 1.5-1.9; 3.5; 9.2 II. 9 65 1 C.sub.2H.sub.5 H CN
.sup.1H NMR: 0.3; 0.5-1.0; 1.3; 1.5-1.8; 1.9; 3.7; 7.5; II. 10 66 1
C.sub.2H.sub.5 CH.sub.3 CN IR: 1056; 1203; 1386; 1463; 1721; 2884;
2928; 2967; 3087; 3174
[0209] Preparation of the Carboxamides I
Example 11
[0210] N-(4'-Chlorophenyl)ethyl-1-cyclopropyl-1-cyanoacetamide
(Comp. I.1 in Table B)
[0211] The solution of 0.62 g (5 mmol) of
1-cyano-1-cyclopropylacetic acid (cf., in this context, Org. Prep.
Proced. Int. (1973), Vol. 5, pp. 25-29) and 0.78 g (5 mmol) of
racemic 1-(4-chlorophenyl)ethylamine in 50 ml of dichloromethane
was treated with 0.5 g (5 mmol) of triethylamine. Then, 0.84 g of
93% strength (4.9 mmol) diethyl cyanophosphonate was added dropwise
at 100.degree. C. and the mixture was stirred for 12 hours at room
temperature. After 50 ml of dichloromethane were added, the mixture
was washed with in each case 100 ml of 2 N sodium hydroxide
solution, 5% strength hydrochloric acid and water. The organic
phase was subsequently dried and concentrated. The residue which
remained was purified by chromatography on silica gel (eluent:
cyclohexane:tert-butyl methyl ether=7:3). 0.4 g (yield 32%) of the
diastereomer mixture of the title compound remained as a solid
residue of m.p. 117-20.degree. C.
Example 12
[0212] N-(4'-chlorophenyl)ethyl
1-cyano-1-(2,2-dichloro-1-methylcyclopropy- l)acetamide (Comp. I.4
in Table B)
[0213] The reaction of
1-cyano-1-(2,2-dichloro-1-methylcylopropyl)acetic acid with
rac-1-(4-chlorophenyl)ethylamine analogously to Example 11 gave the
title compound as a diastereomer mixture.
Example 13
[0214]
N-(4'-Chlorophenyl)ethyl-1-cyano-1-(2,2-dichlorocyclopropyl)-acetam-
ide (Comp. I.5 in Table B)
[0215] The reaction of 1-cyano-1-(2,2-dichlorocylopropyl)acetic
acid with racemic 1-(4-chlorophenyl)ethylamine analogously to
Example 11 gave the title compound as a diastereomer mixture.
Example 14
[0216]
N-(4'-Chlorophenyl)-(R)-ethyl-2-cyano-3-cyclopropylbutanamide
(Comp. I.8 in Table B)
[0217] The reaction of 0.46 g (3 mmol) of
2-cyano-3-cyclopropylbutanoic acid and 0.47 g (3 mmol) of
R-1-(4-chlorophenyl)ethylamine by a method similar to Example 11
gave 0.65 g (yield 75%) of the title compound as a colorless
resin.
Example 15
[0218]
N-(4'-Chlorophenyl)-(R)-ethyl-2-cyano-3-cyclopropyl-3-methylbutanam-
ide (Comp. I.10 in Table B)
[0219] The reaction of 0.5 g (3 mmol) of
2-cyano-3-cyclopropyl-3-methylbut- anoic acid with 0.47 g (3 mmol)
of R-1-(4-chlorophenyl)ethylamine by a method similar to Example 11
gave, after chromatographic purification, 0.7 g (yield 80%) of the
title compound (m.p. 103-6.degree. C.).
Example 16
[0220]
N-(4'-chlorophenyl)-(R)-ethyl-2-cyano-3-(2,2-dichloro-1-methylcyclo-
propyl)butanamide (Comp. I.12 in Table B)
[0221] The reaction of 2 g (8.5 mmol) of
2-cyano-3-(2,2-dichloro-1-methylc- yclopropyl)butanoic acid with
1.3 g (8.5 mmol) of (R)-1-(4-chlorophenyl)et- hylamine by a method
similar to Example 11 gave the [sic] 3.1 g of the title compound
(colorless resin) as a diastereomer mixture.
Example 17
[0222]
N-(4'-Chlorophenyl)-(R)-ethyl-2-cyano-3-(2,2-dichlorocyclopropyl)-3-
-methylbutanamide (Comp. I.15 in Table B)
[0223] The reaction of the acid obtained in Example 6 with
(R)-1-(4-chlorophenyl)ethylamine by a method similar to Example 11
gave the title compound as a diastereomer mixture.
[0224] Other cycloalkylalkanecarboxamides I which were, or can be,
prepared in the same manner are listed in Table B:
24TABLE B 67 Phys. data (NMR in CDCl.sub.3, data in ppm; m.p. in
No. A n R.sup.3 R.sup.4 Z Y * .degree. C.) I. 1 68 0 -- -- 4-Cl CN
rac m.p. 117-120 I. 2 69 0 -- -- 4-Cl CN R m.p. 87-90 I. 3 70 0 --
-- 2,4-Cl.sub.2 CN rac m.p. 138-144 I. 4 71 0 -- -- 4-Cl CN rac I.
5 72 0 -- -- 4-Cl CN rac I. 6 73 1 CH.sub.3 H 4-CH.sub.3CN CN rac
.sup.1H NMR: 0.2-0.9; 1.0; 1.2; 1.5; 2.3; 3.3; 3.5; 5.0; 6.4
(N--H); 7.2 I. 7 74 1 CH.sub.3 H 4-Cl CN rac .sup.1H NMR: 0.3-0.6;
1.0; 3.4; 8.7 I. 8 75 1 CH.sub.3 H 4-Cl CN R .sup.1HNMR: 0.2-0.9;
1.0; 1.2; 1.5; 3.3; 3.5; 5.0; 7.2 I. 9c [sic] 76 1 CH.sub.3 H
2,4-Cl.sub.2 CN rac Oil I. 10 77 1 CH.sub.3 CH.sub.3 4-Cl CN R
.sup.13C NMR: 20-25; 36; 48; 117; 128; 131; 142; 163 I. 11 78 1
CH.sub.3 CH.sub.3 2,4-Cl.sub.2 CN rac m.p. 110-113 I. 12 79 1
CH.sub.3 H 4-Cl CN R .sup.1H NMR: 1.0-1.5; 2.3; 3.3; 3.7; 5.0; 6.5;
7.2 I. 13 80 1 CH.sub.3 H 4-Cl CN rac .sup.1H NMR: 1.0-1.5; 2.3;
3.3; 3.7; 5.0; 6.5; 7.2 I. 14 81 1 CH.sub.3 H 2,4-Cl.sub.2 CN rac
.sup.1H NMR: 1.0-1.5; 2.3; 3.3; 3.7; 5.0; 6.5; 7.2 I. 15 82 1
CH.sub.3 CH.sub.3 4-Cl CN rac I. 16 83 1 CH.sub.3 H 4-CH.sub.3 CN
rac MS: M.sup.+ = 352 I. 17 84 1 CH.sub.3 H 4-OCH.sub.3 CN rac
.sup.1H NMR: 1.2; 1.3; 1.5; 2.3; 3.8; 4.1; 5.0; 6.3; 7.0 I. 18 85 1
CH.sub.3 H 4-Cl CN rac MS: M.sup.+ = 372 I. 19 86 1 CH.sub.3 H 4-Cl
CN R .sup.1H NMR: 1.2; 1.4; 1.5; 2.3; 3.7; 5.1; 6.5; 7.2 I. 20 87 1
CH.sub.3 CH.sub.3 4-Cl CN rac MS: M.sup.+ = 306 I. 21 88 1 H H 4-Cl
CN rac MS: M.sup.+ = 344 I. 22 89 1 H H 4-Cl CN R MS: M.sup.+ = 344
I. 23 90 0 -- -- 2,4-Cl.sub.2 CN R m.p. 140-145 I. 24 91 1 CH.sub.3
CH.sub.3 2,4-Cl.sub.2 CN R m.p. 75-80 I. 25 92 0 -- -- 4-Cl CN rac
m.p. 95-100 I. 26 93 0 -- -- 4-Cl CN R m.p. 130-132 I. 27 94 0 --
-- 2,4-Cl.sub.2 CN rac m.p. 110-115 I. 28 95 0 -- -- 2,4-Cl.sub.2
CN R m.p. 120-123 I. 29 96 1 C.sub.2H.sub.5 H 4-Cl CN R .sup.1H
NMR: 0.2-0.5; 0.7; 0.9-1.1; 1.4; 1.6; 3.5; 5.1; 6.5; 7.3 I. 30 97 1
C.sub.2H.sub.5 H 2,4-Cl.sub.2 CN R .sup.1H NMR: 0.5; 0.7; 0.9-1.1;
1.4; 1.5; 3.5; 5.3; 6.7; 7.2; 7.4 I. 31 98 1 C.sub.2H.sub.5
CH.sub.3 4-Cl CN R .sup.1H NMR: 0.2-0.5; 0.7-1.0; 1.2; 1.5; 3.3;
5.1; 6.2; 7.3; I. 32 99 1 C.sub.2H.sub.5 CH.sub.3 2,4-Cl.sub.2 CN R
.sup.1H NMR: 0.3-0.5; 0.7-1.0; 1.4; 1.6; 3.4; 5.4; 6.5; 7.2;
1.4
[0225]
25TABLE C (* = configuration at the atom labeled "*" ; rac =
racemic; R = R configuration) 100 Phys. data (NMR in CDCl.sub.3,
No. A n R.sup.3 R.sup.4 Y * data in ppm; m.p. in .degree. C.) I. 33
101 0 -- -- CN rac .sup.1H NMR: 0.8-1.3; 1.7; 3.6; 5.3; 6.5; 7.4;
7.8 I. 34 102 1 CH.sub.3 H CN rac m.p. 90-95 I. 35 103 1 CH.sub.3 H
CN R m.p. 95-98 I. 36 104 1 CH.sub.3 CH.sub.3 CN rac m.p. 145-148
I. 37 105 1 CH.sub.3 CH.sub.3 CN R m.p. 105-108 I. 38 106 1
C.sub.2H.sub.5 H CN R .sup.1H NMR: 0.4; 0.9-1.1; 1.4; 1.6; 3.5;
5.3; 6.6; 7.5; 7.8 I. 39 107 1 C.sub.2H.sub.5 CH.sub.3 CN R .sup.1H
NMR: 0.4; 0.7-1.0; 1.4; 1.6; 3.4; 5.3; 6.4; 7.5; 7.8
Use Examples
[0226] The fungicidal action of the compounds of the formula I
against harmful fungi was demonstrated by the following greenhouse
experiments:
[0227] The active ingredients were formulated as a 20% emulsion in
a mixture of 70% by weight of cyclohexanone, 20% by weight of
Nekanil.RTM. LN (Lutensol.RTM. AP6, wetter with emulsifying and
dispersant action based on ethoxylated alkylphenols) and 10% by
weight of Emulphor.RTM. EL (Emulan.RTM. EL, emulsifier based on
ethoxylated fatty alcohols) and diluted with water to give the
desired concentration.
[0228] 1. Activity Against Pyricularia oryzae (Protective)
[0229] Leaves of rice seedlings (cultivar "Tai-Nong 67") in pots
were treated with the aqueous preparation of the active ingredients
(comprising 250 ppm). After approximately 24 hours, the plants were
inoculated with an aqueous spore suspension of Pyricularia oryzae.
The plants which had been treated in this manner were placed for 6
days into controlled-environment cabinets at 22-24.degree. C. and a
relative atmospheric humidity of 95 to 99%. The extent of the
disease which had developed on the leaves was subsequently
determined visually.
[0230] In this test, the plants which had been treated with the
compounds I.7, I.8 and I.10 according to the invention showed a
disease level of 10% or less, while the disease level of the
untreated plants was 80%.
[0231] 2. Systemic Activity Against Pyricularia oryzae
[0232] Pregerminated rice (cultivar "Tai-Nong 67") was grown in a
hydroponic system with Hoagland solution until it had reached the
two-leaf stage. Then, the aqueous preparation of the active
ingredient (comprising 50 ppm) was poured next to the roots. After
the plants had grown on in the greenhouse for five days, they were
inoculated with an aqueous spore suspension of Pyricularia oryzae.
The plants which had been treated in this manner were placed for 6
days into controlled-environment cabinets at 22-24.degree. C. and a
relative atmospheric humidity of 95 to 99%. The extent of the
disease which had developed on the leaves was subsequently
determined visually.
[0233] In this test, the plants which had been treated with the
compounds I.1, I.2, I.3, I.7, I.8 and I.10 according to the
invention showed a disease level of 15% or less, while the disease
level of the untreated plants was 80%.
[0234] 3. Comparison Against U.S. Pat. No. 4,946,867--Systemic
Activity Against Pyricularia oryzae
[0235] The improved fungicidal activity of the compounds of the
formula I according to the invention as compared to the
structurally most similar compound of the prior art (U.S. Pat. No.
4,946,867) was demonstrated by the following experiment. The
compound A (compound 9 from Table 1), known from U.S. Pat. No.
4,946,867, served as comparative compound 108
[0236] The experiment was carried out similarly to Use Example 2
using an aqueous active compound preparation containing 50 or 10
ppm.
26 % infestation of leaves after application of an aqueous active
compound preparation containing . . . ppm Active compound 50 10
(according to the 5 20 invention) I.1 (comparative example) 40 65
A
[0237] Untreated (control) plants showed an infestation of 80%.
* * * * *