U.S. patent application number 11/340977 was filed with the patent office on 2006-06-22 for 7-(r)-aminotriazolopyrimidines, their preparation and their use for controlling phytopathogenic fungi.
Invention is credited to Eberhard Ammermann, Jordi Tormo I. Blasco, Oliver Cullmann, Klaus Ditrich, Markus Gewehr, Wassilios Grammenos, Thomas Grote, Andreas Gypser, Gisela Lorenz, Bernd Muller, Joachim Rheinheimer, Ingo Rose, Hubert Sauter, Peter Schafer, Frank Schieweck, Reinhard Stierl, Siegfried Strathmann.
Application Number | 20060135538 11/340977 |
Document ID | / |
Family ID | 7663068 |
Filed Date | 2006-06-22 |
United States Patent
Application |
20060135538 |
Kind Code |
A1 |
Blasco; Jordi Tormo I. ; et
al. |
June 22, 2006 |
7-(R)-aminotriazolopyrimidines, their preparation and their use for
controlling phytopathogenic fungi
Abstract
7-(R)-Aminotriazolopyrimidines of the formula I ##STR1## where
the substituents and the index are as defined below: R.sup.1 is
hydrogen or methyl; R.sup.2 is methyl; R.sup.3 is
C.sub.2-C.sub.1o-alkyl, C.sub.1-C.sub.4-alkoxymethyl,
C.sub.3-C.sub.1o-cycloalkyl; R.sup.4 is halogen, Cl-C.sub.4-alkyl,
C.sub.1-C.sub.4-haloalkyl or Cl-C.sub.4-alkoxy; n is a number from
1 to 5; Y is halogen, cyano, Cl-C.sub.4-alkyl or
C.sub.l-C.sub.4-alkoxy; where * is a center of chirality in the R
configuration, processes for preparing these compounds,
compositions comprising them and their use for controlling harmful
fungi are described.
Inventors: |
Blasco; Jordi Tormo I.;
(Limburgerhof, DE) ; Ditrich; Klaus; (Gonnheim,
DE) ; Sauter; Hubert; (Mannheim, DE) ;
Cullmann; Oliver; (Heppenheim, DE) ; Gewehr;
Markus; (Kastellaun, DE) ; Grammenos; Wassilios;
(Ludwigshafen, DE) ; Muller; Bernd; (Frankenthal,
DE) ; Grote; Thomas; (Wachenheim, DE) ;
Gypser; Andreas; (Mannheim, DE) ; Rheinheimer;
Joachim; (Ludwigshafen, DE) ; Rose; Ingo;
(Mannheim, DE) ; Schafer; Peter; (Ottersheim,
DE) ; Schieweck; Frank; (Hessheim, DE) ;
Ammermann; Eberhard; (Heppenheim, DE) ; Strathmann;
Siegfried; (Limburgerhof, DE) ; Lorenz; Gisela;
(Hambach, DE) ; Stierl; Reinhard; (Mutterstadt,
DE) |
Correspondence
Address: |
NOVAK DRUCE DELUCA & QUIGG, LLP
1300 EYE STREET NW
SUITE 400 EAST
WASHINGTON
DC
20005
US
|
Family ID: |
7663068 |
Appl. No.: |
11/340977 |
Filed: |
January 30, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10416467 |
May 12, 2003 |
6855718 |
|
|
PCT/EP01/12977 |
Nov 9, 2001 |
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11340977 |
Jan 30, 2006 |
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Current U.S.
Class: |
514/259.31 ;
544/280 |
Current CPC
Class: |
A01N 43/90 20130101;
C07D 487/04 20130101 |
Class at
Publication: |
514/259.31 ;
544/280 |
International
Class: |
A01N 43/90 20060101
A01N043/90; C07D 487/04 20060101 C07D487/04 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 13, 2000 |
DE |
10056101.2 |
Claims
1. A compound of formula I ##STR8## where R.sup.1 is hydrogen or
methyl; R.sup.2 is methyl; R.sup.3 is C.sub.2-C.sub.10-alkyl;
C.sub.1-C.sub.4-alkoxymethyl; C.sub.3-C.sub.10-cycloalkyl; R.sup.4
.sub.n is 2,6-dichloro. 2-chloro-6-fluoro or 2-chloro: y is
halogen, cyano, C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-alkoxy;
and where * is a center of chirality in the R configuration,
excluding the compounds
sec-butyl-[5-chloro-6-(2-chloro-6-fluoro-phenyl)-
[1,2,4]triazolo[1,5-a]pyrimidin-7-yI]-amine and
[5-chloro-6-(2-chloro-6-fluoro- phenyl)-[1 ,2,4]triazolo[1
,5-a]pyrimidin-7-yl]-( 1 ,2,2-trimethyl-propyl)-a mine.
2. A compound of the formula I as claimed in claim 1, where R.sup.1
is hydrogen; R.sup.3 is C.sub.2-C.sub.10-alkyl or
C.sub.3-C.sub.10-cycloalkyl; and Y is chlorine.
3. A compound of the formula I as claimed in claim 2, where R.sup.3
is tert-butyl or isopropyl.
4. A compound of the formula I as claimed in claim 1, where
(R.sup.4).sub.n, has the following meaning:
5. A process for preparing the compounds I as claimed in claim 1,
which comprises reacting a 7-halotriazolopyrimidine of the formula
II, ##STR9## in which the substituents R.sup.4 and Y and the index
n are as defined in claim 1, with a (R)-configured amine of the
formula III ##STR10## in which the substituents,R.sup.1,R.sup.2 and
R.sup.3 are as defined in claim 1.
6. A process as claimed in claim 5, wherein
(R)-3,3-dimethylbut-2-ylamine or (R)-3-methylbut-2-ylamine is
used.
7. A process as claimed in claim 5, wherein a (R)-configured amine
of the formula III is prepared by i) enantioselectively acylating,
in the presence of a hydrolase, a racemic amine III with an ester
whose acid component carries a fluorine, nitrogen, oxygen or sulfur
atom in the vicinity of the carbonyl carbon, ii) separating the
mixture of (S)-amine III and acylated (R)-amine III and iii)
subjecting the acylated (R)-amine III to an amide cleavage.
8. A fungicidal composition, comprising solid and/or liquid
carriers and a fungicidally effective amount of at least one
compound of the formula I as claimed in claim 1.
9. A method for controlling phytopathogenic fungi which comprises
treating the fungi or the materials, plants, seeds or the soil
threatened by fungal attack with a fungicidally effective amount of
at least one compound of the formula I ##STR11## where R.sup.1 is
hydrogen or methyl; R.sup.2 is methyl; R.sup.3 is
C.sub.2-C.sub.10-alkyl; C.sub.1-C.sub.4-alkoxymethyl;
C.sub.3-C,.sub.0-cycloalkyl; R.sup.4.sub.n is 2,6-dichloro,
2-chloro-6-fluoro or 2-chloro; y is halogen, cyano,
C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-alkoxy; where * is a
center of chirality in the R configuration.
10. The method of claim 9, where R.sup.4.sub.n is 2,6-dichloro or
2- chloro-6-fluoro.
11. The method of claim 9, where the compound of formula I has the
formula IA ##STR12## where R.sub.1 is hydrogen, R.sup.3 is
CH.sub.2CH.sub.3 and R.sup.4.sub.n is 2-chloro.
12. The method of claim 9, where the compound of formula I has the
formula IA ##STR13## where R.sup.1 is hydrogen, R.sup.3 is
CH(CH.sub.3).sub.2 and R.sup.4.sub.n is 2-chloro.
13. The method of claim 9, where the compound of formula I has the
formula IA ##STR14## where R.sup.1 is hydrogen, R.sup.3 is
C(CH.sub.3).sub.3 and R.sup.4.sub.n is 2-chloro.
14. The compound of claim 1, having the formula IA ##STR15## where
R.sup.1 is hydrogen, R.sup.3 is CH.sub.2CH.sub.3 and R.sup.4.sub.n
is 2-chloro.
15. The compound of claim 1, having the formula IA ##STR16## where
R.sup.1 is hydrogen, R.sup.3 is CH(CH.sub.3).sub.2 and
R.sup.4.sub.n is 2-chloro.
16. The compound of claim 1, having the formula IA ##STR17## where
R.sup.1 is hydrogen, R.sup.3 is C(CH.sub.3).sub.3 and R.sup.4.sub.n
is 2-chloro.
Description
[0001] The invention relates to 7-(R)-aminotriazolopyrimidines of
the formula I ##STR2##
[0002] where the substituents and the index are as defined
below:
[0003] R.sup.1 is hydrogen or methyl;
[0004] R.sup.2 is methyl;
[0005] R.sup.3 is C.sub.2-C.sub.10-alkyl, Cl-C.sub.4-alkoxymethyl,
C.sub.3-C.sub.1o-cycloalkyl;
[0006] R.sup.4 is halogen, C.sub.1-C.sub.4-alkyl,
C.sub.1-C.sub.4-haloalkyl or Cl-C.sub.4-alkoxy;
[0007] n is a number from 1 to 5;
[0008] Y is halogen, cyano, C.sub.l-C.sub.4-alkyl or
C.sub.l-C.sub.4-alkoxy;
where * is a center of chirality in the R configuration.
[0009] Furthermore, the invention relates to a process for
preparing the compounds of the formula I, to compositions for
controlling phytopathogenic fungi, which compositions comprise the
compounds I, and to the use of the compounds I for controlling
phytopathogenic fungi.
[0010] WO-A 98/46607 discloses racemic
5-chloro-7-amino-6-(2,4,6-trifluorophenyl)-1,2,4-triazolo[l1,5-a]-pyrimdi-
nes. Furthermore, on page 7, paragraphs 1 and 2, of WO-A 98/46607,
it is mentioned quite generally that, in the case of compounds
having a chiral amine moiety, the respective S-enantiomers would in
each case have particularly interesting fungicidal properties.
[0011] WO-A 98/46608 discloses racemic
5-halo-7-(fluoroalkyl)amino-6-phenyl-1,2,4-triazolo[1,5-a]pyrimidines,
where the a-C-atom of the 7-(fluoroalkyl)amino moiety is chiral and
carries a CF.sub.3 group. In this publication, it is taught that
the respective S-enantiomers would in each case have particularly
interesting fungicidal properties.
[0012] It is an object of the present invention to provide
compounds having improved activity and/or a broader activity
spectrum.
[0013] Surprisingly, we have found that this object is achieved by
compounds carrying a R-configured halogen-free amino radical in the
7-position.
[0014] The meanings listed above are collective terms for
individual enumerations of the individual group members. All carbon
chains can be straight-chain or branched. Halogenated substituents
preferably carry 1 to 5 identical or different halogen atoms.
[0015] In the definitions of the symbols given in the formulae
above, collective terms are used which, in general, represent the
following substituents:
halogen: fluorine, chlorine, bromine and iodine;
[0016] alkyl: saturated straight-chain or branched hydrocarbon
radicals having 1 to 4, 6, 8 or 10 carbon atoms, for example
C.sub.1-C.sub.6-alkyl, such as methyl, ethyl, propyl,
1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl,
1,1-dimethylethyl, 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, 1,2,2-trimethylpropyl,
1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl;
alkoxy: straight-chain or branched alkyl groups having 1 to 4
carbon atoms (as mentioned above) which are attached to the
skeleton via an oxygen atom (--0--);
[0017] alkenyl: unsaturated straight-chain or branched hydrocarbon
radicals having 2 to 4, 6, 8 or 10 carbon atoms and a double bond
in any position, for example C.sub.2-C.sub.6-alkenyl, such as
ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl,
2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl,
1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl,
3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl,
3-methyl-l-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl,
3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl,
3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl,
1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl,
1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl,
3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl,
2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl,
1-methyl-2-pentenyl, 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,
1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl,
1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl,
1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl,
1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl,
2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl,
2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl,
3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl,
1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl,
2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl,
1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and
1-ethyl-2-methyl-2-propenyl;
[0018] alkynyl: straight-chain or branched hydrocarbon groups
having 2 to 4, 6, 8 or 10 carbon atoms and a triple bond in any
position, for example C.sub.2-C.sub.6-alkynyl, such as ethynyl,
1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl,
1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl,
4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl,
2-methyl-3-butynyl, 3-methyl-1-butynyl, 1,1-dimethyl-2-propynyl,
1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl,
5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,
1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl,
3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl,
4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl,
1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl,
2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl,
1-ethyl-3-butynyl, 2-ethyl-3-butynyl and
1-ethyl-l-methyl-2-propynyl;
cycloalkyl: monocyclic saturated hydrocarbon groups having 3 to 10
carbon ring members, for example C.sub.3-C8-cycloalkyl, such as
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and
cyclooctyl.
[0019] The compounds I can preferably be prepared by reacting a
7-halotriazolopyrimidine of the formula II in which the
substituents R.sup.4 and Y and the index n are as defined in claim
1 with (R)-configured amines of the formula III. ##STR3##
[0020] The reaction of the compound II with (R)-configured amines
of the formula III is carried out, for example, in an inert solvent
or diluent, such as a chlorinated hydrocarbon (in particular
dichloromethane or trichloromethane), acetone, acetonitrile,
dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidone, an
aromatic hydrocarbon (in particular toluene or chlorobenzene) or an
ether (in particular tetrahydrofuran, dimethoxyethane or
dioxane).
[0021] In general, the reaction is carried out using a base (for
example sodium carbonate, potassium carbonate, sodium hydroxide,
potassium hydroxide, sodium hydride, potassium hydride or, in
particular, a tertiary amine). Tertiary amines such as
triethylamine, ethyldiisopropylamine or diazabicycloundecene have
been found to be particularly suitable. The bases are generally
employed in equimolar amounts or in excess. Moreover, it may be
advantageous to add a catalytic amount of a crown ether (for
example 18-crown-6 or 15-crown-5).
[0022] The reaction temperature is generally in the range from 0 to
100.degree. C., preferably from 10 to 35.degree. C. The reaction
can, for example, be carried out at room temperature.
[0023] To isolate and purify the compounds according to the
invention, it is possible to use customary methods such as
extraction, chromatography or recrystallization.
[0024] The 7-halotriazolopyrimidines II required for preparing the
compounds I are known from the literature or can be prepared by
methods known from the literature [cf. WO-A 98/46607; EP-A 550
113]. They are usually prepared by reacting 3-amino-1,2,4-triazole
with 2-phenylmalonic esters or 2-phenylacetic esters of the formula
IV ##STR4## in which R.sup.4 and the index n are as defined for
formula I and R is C.sub.1-C.sub.4-alkyl. In this manner, it is
possible, starting from 2-phenylmalonic esters (IVa) or diketones
(IVb), to obtain 5,7-dihydroxy-6-phenyltriazolopyrimidines and 5
-alkyl-7-hydroxy-6-phenyltriazolopyrimidines, respectively. If the
easily accessible 2-phenylacetoacetic esters (IVb where R=CH.sub.3)
are used, 5-methyl-7-hydroxy-6-phenyltriazolopyrimidines are
obtained [cf. Chem. Pharm. Bull. 9 (1961), 801]. The preparation of
the starting materials IV is described in EP-A 10 02 788.
[0025] The resulting 5,7-dihydroxy-6-phenyltriazolopyrimidines and
5-alkyl-7-hydroxy-6-phenyltriazolopyrimidines are reacted with
halogenating agents to give the 7-halotriazolopyrimidines of the
formula II. Preference is given to using chlorinating or
brominating agents, such as phosphorus oxybromide, phosphorus
oxychloride, thionyl chloride, thionyl bromide or sulfuryl
chloride. The reaction can be carried out in the absence or
presence of a solvent. Customary reaction temperatures are from 0
to 150.degree. C., preferably from 80 to 125.degree. C.
[0026] It is furthermore possible to prepare compounds I in which Y
is alkyl by the method described in US-A 5,994,360 - starting from
5,7-dichloro-6-phenyltriazolopyrimidines, by chlorine/amine
exchange in the 7-position and substitution of the chorine by a
malonic acid radical, followed by decarboxylation.
[0027] Compounds I in which Y is methoxy can be prepared
advantageously by the process described in WO-A 99/41255 - starting
from 5,7-dichloro-6-phenyltriazolopyrimidines, by chlorine/amine
exchange in the 7-position and substitution of the chlorine by
methoxide.
[0028] R-configured amines III can be prepared advantageously by
the route shown in scheme 1 using (R)-3,3-dimethylbut-2-amine
(R-DMBA) as an example. ##STR5##
[0029] The above synthesis uses racemic 3,3-dimethylbut-2-amine
(rac-DMBA), which is obtainable as described in J. Am. Chem. Soc.,
1939(61), p. 3500 and J. Am. Chem. Soc., 1941(63), p. 3135, as
starting material. Resolution of the racemate is carried out by the
process described in WO-A 95/08636 and wO-A 97/10201. This process
involves the following steps: [0030] 1) racemic
3,3-dimethylbut-2-ylamine is enantioselectively acylated in the
presence of a hydrolase, using an ester whose acid component
carries a fluorine, nitrogen, oxygen or sulfur atom in the vicinity
of the carbonyl carbon, [0031] 2) the mixture of
(S)-3,3-dimethylbut-2-ylamine (S-DMBA) and acylated
(R)-3,3-dimethylbut-2-ylamine (R-DMBamide) is then separated and
[0032] 3) the acylated (R)-3,3-dimethylbut-2-ylamine is subjected
to amide cleavage.
[0033] The publications WO-A 95/08636 and WO-A 97/10201 give a
specific list of the esters and hydrolases which are particularly
suitable for racemate resolution, so that an explicit illustration
can be dispensed with here.
[0034] The hydrolases used are preferably proteases and in
particular lipases. Particularly suitable are lipases from
Pseudomonas, for example Amano P, or the lipase from Pseudomonas
spec. DSM 8246. Other particularly suitable hydrolases are the
enzymes available from Novo Nordisk (Enzyme Toolbox), in particular
the lipases SP 523, SP 524, SP 525, SP 526 and Novozym.RTM.
435.
[0035] The enzyme can be used in native or immobilized form.
[0036] Amines of the formula III are either commercially available
or can be obtained by optical resolution of the racemate as
illustrated in scheme 1.
[0037] Preference is given to compounds I in which R.sup.1 is
hydrogen or methyl, in particular hydrogen.
[0038] Moreover, preference is given to compounds I in which
R.sup.2 is methyl.
[0039] In addition, preference is also given to compounds of the
formula IA: ##STR6##
[0040] In the formula IA, R.sup.1, R.sup.3 and (R.sup.4).sub.n, are
as defined for formula I.
[0041] Likewise, preference is given to compounds I and IA in which
R.sup.3 is ethyl, isopropyl or tert-butyl, in particular
tert-butyl.
[0042] Preference is given to compounds of the formula I in which n
is 2 or 3, in particular 3.
[0043] The substituents and the index n in the formula I are
preferably as defined below: [0044] R.sup.4 is fluorine, chlorine,
methyl or methoxy, in particular fluorine; [0045] n is the number 2
or 3, in particular the number 3; [0046] Y is fluorine, chlorine,
bromine, methyl or methoxy, in particular chlorine.
[0047] With respect to (R.sup.4).sub.n, particular preference is
given to the following combinations of substituents:
[0048] 2,6-difluoro;
[0049] 2-chloro, 6-fluoro;
[0050] 2,6-dichloro;
[0051] 2-methyl-4-fluoro;
[0052] 2-methyl-6-fluoro;
[0053] 2,4,6-trifluoro;
[0054] 2,6-difluoro-4-methyl; 2,6-difluoro-4-methoxy;
[0055] pentafluoro.
[0056] Particular preference is given to the compound
(R)-5-chloro-7-(3,3-dimethylbut-2-yl)amino-6-(2,4,6-trifluoro-phenyl)-1,2-
,4-triazolo[1,5-a]pyrimidine.
[0057] In particular with a view to their use, preference is given
to the compounds I compiled in the tables below. Moreover, the
groups mentioned for a substituent in the tables are on their own,
independently of the combination in which they are mentioned, a
particularly preferred embodiment of the substituent in
question.
TABLE 1
[0058] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is ethyl and the combination of the radicals (R.sup.4)n for
a compound corresponds in each case to one row of Table A
TABLE 2
[0059] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is isopropyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 3
[0060] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is tert-butyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 4
[0061] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is n-propyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 5
[0062] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is n-butyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 6
[0063] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is n-pentyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 7
[0064] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is n-hexyl and the combination of the radicals
(R.sup.4).sub.n, for a compound corresponds in each case to one row
of Table A
TABLE 8
[0065] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is n-heptyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 9
[0066] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is n-octyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 10
[0067] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is n-nonyl and the combination of the radicals (R.sup.4
).sub.n for a compound corresponds in each case to one row of Table
A
TABLE 11
[0068] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is isobutyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 12
[0069] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is cyclopropyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 13
[0070] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is cyclohexyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 14
[0071] Compounds of the formula IA in which R.sup.1 is hydrogen,
R.sup.3 is methoxymethyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 15
[0072] Compounds of the formula IA in which R.sup.1 is methyl,
R.sup.3 is ethyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A
TABLE 16
[0073] Compounds of the formula IA in which R.sup.1 is methyl,
R.sup.3 is n-hexyl and the combination of the radicals
(R.sup.4).sub.n for a compound corresponds in each case to one row
of Table A TABLE-US-00001 TABLE A No. (R.sup.4).sub.n A-1 2-Cl-6-F
A-2 2,6-F.sub.2 A-3 2,6-Cl.sub.2 A-4 2-CH.sub.3-6-F A-5
2,4,6-F.sub.3 A-6 2,6-F.sub.2-4-OCH.sub.3 A-7 F.sub.5 A-8
2-CH.sub.3-4-F A-9 2-CF.sub.3 A-10 2-OCH.sub.3-6-F A-11
2-OCH.sub.3-4,6-F.sub.2
[0074] The novel compounds I have excellent activity against a
broad spectrum of phytopathogenic fungi, especially from the
classes of Ascomycetes and Basidiomycetes, and they can be employed
as foliar- and soil-acting fungicides. Some of them have remarkably
high systemic mobility and activity after soil application and in
particular also after foliar application.
[0075] They are especially important for controlling a large number
of fungi in a variety of crop plants such as wheat, rye, barley,
oats, rice, corn, grass, bananas, cotton, soy, coffee, sugar cane,
grapevines, fruit species, ornamentals and vegetable species such
as cucumbers, beans, tomatoes, potatoes and cucurbits, and also in
the seeds of these plants.
[0076] Specifically, they are suitable for controlling the
following plant diseases: [0077] Alternaria species, Podosphaera
species, Sclerotinia species, Physalospora canker in vegetables and
fruit, [0078] Botrytis cinerea (gray mold) in strawberries,
vegetables, ornamentals and grapevines, [0079] Corynespora
cassiicola in cucumbers, [0080] Colletotrichum species in fruit and
vegetables, [0081] Diplocarpon rosae in roses, [0082] Elsinoe
fawcetti and Diaporthe citri in citrus fruits, [0083] Sphaerotheca
species in cucurbits, strawberries and roses, [0084] Cercospora
species in groundnuts, sugar beet and aubergines, [0085] Erysiphe
cichoracearum in cucurbits, [0086] Leveillula taurica in peppers,
tomatoes and aubergines, [0087] Mycosphaerella species in apples
and Japanese apricot, [0088] Phyllactinia kakicola, Gloesporium
kaki, in Japanese apricot, [0089] Gymnosporangium yamadae,
Leptothyrium pomi, Podosphaera leucotricha and Gloedes pomigena in
apples, [0090] Cladosporium carpophilum in pears and Japanese
apricot, [0091] Phomopsis species in pears, [0092] Phytophthora
species in citrus fruits, potatoes, onions, in particular
Phytophthora infestans in potatoes and tomatoes, [0093] Blumeria
graminis (powdery mildew) in cereals, [0094] Fusarium and
Verticillium species in a variety of plants, [0095] Glomerella
cingulata in tea, [0096] Drechslera and Bipolaris species in
cereals and rice, [0097] Mycosphaerella species in bananas and
groundnuts, [0098] Plasmopara viticola in grapevines, [0099]
Personospora species in onions, spinach and chrysanthemums, [0100]
Phaeoisariopsis vitis and Sphaceloma ampelina in grapefruits,
[0101] Pseudocercosporella herpotrichoides in wheat and barley,
[0102] Pseudoperonospora species in hops and cucumbers, [0103]
Puccinia species and Typhula species in cereals and lawns, [0104]
Pyricularia oryzae in rice, [0105] Rhizoctonia species in cotton,
rice and lawns, [0106] Stagonospora nodorum and Septoria tritici in
wheat, [0107] Uncinula necator in gravevines, [0108] Ustilago
species in cereals and sugar cane and [0109] Venturia species
(scab) in apples and pears.
[0110] The compounds I are also suitable for controlling harmful
fungi such as Paecilomyces variotii in the protection of materials
(for example wood, paper, paint dispersions, fibers or tissues) and
in the protection of stored products.
[0111] The compounds I are employed by treating the fungi or the
plants, seeds, materials or the soil to be protected against fungal
attack with a fungicidally effective amount of the active
compounds. The application may be carried out before or after the
infection of the materials, plants or seeds by the fungi.
[0112] The fungicidal compositions generally comprise from 0.1 to
95, preferably from 0.5 to 90, % by weight of active compound.
[0113] For use in crop protection, the application rates are,
depending on the kind of effect desired, from 0.01 to 2.0 kg of
active compound per ha.
[0114] The treatment of seeds generally requires active compound
quantities of from 0.001 to 0.1 g, preferably from 0.01 to 0.05 g,
per kilogram of seed.
[0115] For use in the protection of materials or stored products,
the active compound application rate depends on the kind of
application area and desired effect. Customary application rates in
the protection of materials are, for example, from 0.001 g to 2 kg,
preferably from 0.005 g to 1 kg, of active compound per cubic meter
of treated material.
[0116] The compounds I can be converted into the customary
formulations, e.g. solutions, emulsions, suspensions, dusts,
powders, pastes and granules. The use form depends on the specific
intended use; in any case, it should ensure fine and uniform
distribution of the compound according to the invention.
[0117] The formulations are prepared in a known manner, e.g. by.
extending the active compound with solvents and/or carriers, if
desired using emulsifiers and dispersants, it also being possible
to use other organic solvents as auxiliary solvents if the diluent
used is water. Suitable auxiliaries for this purpose are
essentially: solvents such as aromatics (e.g. xylene), chlorinated
aromatics (e.g. chlorobenzenes), paraffins (e.g. mineral oil
fractions), alcohols (e.g. methanol, butanol), ketones (e.g.
cyclohexanone), amines (e.g. ethanolamine, dimethylformamide) and
water; carriers such as ground natural minerals (e.g. kaolins,
clays, talc, chalk) and ground synthetic minerals (e.g. finely
divided silica, silicates); emulsifiers such as nonionic and
anionic emulsifiers (e.g. polyoxyethylene fatty alcohol ethers,
alkylsulfonates and arylsulfonates), and dispersants such as
lignosulfite waste liquors and methylcellulose.
[0118] Suitable surfactants are the alkali metal, alkaline earth
metal, and ammonium salts of lignosulfonic acid,
naphthalenesulfonic acid, phenolsulfonic acid,
dibutylnaphthalenesulfonic acid, alkylarylsulfonates,
alkylsulfates, alkylsulfonates, fatty alcohol sulfates and fatty
acids and alkali metal salts and alkaline earth metal salts
thereof, salts of sulfated fatty alcohol glycol ethers,
condensation products of sulfonated naphthalene and naphthalene
derivatives with formaldehyde, condensation products of naphthalene
or of naphthalene sulfonic acid with phenol and formaldehyde,
polyoxyethylene octylphenol ethers, ethoxylated isooctylphenol,
octylphenol, nonylphenol, alkylphenol polyglycol ethers,
tributylphenyl polyglycol ethers, alkylaryl polyether alcohols,
isotridecyl alcohol, fatty alcohol ethylene oxide condensates,
ethoxylated castor oil, polyoxyethylene alkyl ethers, ethoxylated
polyoxypropylene, lauryl alcohol polyglycol ether acetal, sorbitol
esters, lignosulfite waste liquors and methylcellulose.
[0119] Suitable for preparing directly sprayable solutions,
emulsions, pastes or oil dispersions are petroleum fractions having
medium to high boiling points, such as kerosene or diesel fuel,
furthermore coal-tar oils and oils of plant or animal origin,
aliphatic, cyclic and aromatic hydrocarbons, for example benzene,
toluene, xylene, paraffin, tetrahydronaphthalene, alkylated
naphthalene or derivatives thereof, methanol, ethanol, propanol,
butanol, chloroform, carbon tetrachloride, cyclohexanol,
cyclohexanone, chlorobenzene, isophorone, strongly polar solvents,
for example dimethylformamide, dimethyl sulfoxide,
N-methylpyrrolidone, and water.
[0120] Powders, compositions for broadcasting and dusts can be
prepared by mixing or joint grinding of the active substances with
a solid carrier.
[0121] Granules, for example coated granules, impregnated granules
and homogeneous granules, can be prepared by binding the active
compounds to solid carriers. Solid carriers are, for example,
mineral earths, such as silica gel, silicas, silicates, talc,
kaolin, attaclay, limestone, lime, chalk, bole, loess, clay,
dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate,
magnesium oxide, ground synthetic materials, 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 nutshell meal, cellulose powders and other solid
carriers.
[0122] The formulations generally comprise from 0.01 to 95% by
weight, preferably from 0.1 to 90% by weight, of the active
compound. The active compounds are employed in a purity of from 90%
to 100%, preferably from 95% to 100% (according to the NMR
spectrum).
Examples of formulations are:
[0123] I. 5 parts by weight of a compound according to the
invention are intimately mixed with 95 parts by weight of finely
divided kaolin. This affords a dust comprising 5% by weight of the
active compound. [0124] II. 30 parts by weight of a compound
according to the invention are intimately mixed with a mixture of
92 parts by weight of pulverulent silica gel and 8 parts by weight
of paraffin oil which have been sprayed onto the surface of this
silica gel. This affords an active compound preparation having good
adhesive properties (active compound content 23% by weight). [0125]
III. 10 parts by weight of a compound according to the invention
are dissolved in a mixture comprising 90 parts by weight.of xylene,
6 parts by weight of the addition product of 8 to 10 mol of
ethylene oxide to 1 mol of oleic acid N-monoethanolamide, 2 parts
by weight of the calcium salt of dodecylbenzenesulfonic acid and 2
parts by weight of the addition product of 40 mol of ethylene oxide
to 1 mol of castor oil (active compound content 9% by weight).
[0126] IV. 20 parts by weight of a compound according to the
invention are dissolved in a mixture comprising 60 parts by weight
of cyclohexanone, 30 parts by weight of isobutanol, 5 parts by
weight of the addition product of 7 mol of ethylene oxide to 1 mol
of isooctylphenol and 5 parts by weight of the addition product of
40 mol of ethylene oxide to 1 mol of castor oil (active compound
content 16% by weight).
[0127] V. 80 parts by weight of a compound according to the
invention are intimately mixed with 3 parts by weight of the sodium
salt of diisobutylnaphthalene-alpha-sulfonic acid, 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, well
mixed and ground in a hammer mill (active compound content 80% by
weight). [0128] VI. 90 parts by weight of a compound according to
the invention are mixed with 10 parts by weight of
N-methyl-a-pyrrolidone, affording a solution which is suitable for
use in the form of very small drops (active compound content 90% by
weight). [0129] VII. 20 parts by weight of a compound according to
the invention are dissolved in a mixture comprising 40 parts by
weight of cyclohexanone, 30 parts by weight of isobutanol, 20 parts
by weight of the addition product 6f 7 mol of ethylene oxide to 1
mol of isooctylphenol and 10 parts by weight of the addition
product of 40 mol of ethylene oxide to 1 mol of castor oil. The
solution is poured onto 100,000 parts by weight of water and finely
dispersed therein, affording an aqueous dispersion comprising 0.02%
by weight of active compound. [0130] VIII. 20 parts by weight of a
compound according to the invention are intimately mixed with 3
parts by weight of the sodium salt of
diisobutylnaphthalene-a-sulfonic acid, 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 ground in a
hammer mill. The mixture is finely dispersed in 20,000 parts by
weight of water, affording a spray liquor comprising 0.1% by weight
of active compound. [0131] IX. 10 parts by weight of the compound
according to the invention are dissolved in 63 parts by weight of
cyclohexanone, 27 parts by weight of dispersant (for example a
mixture of 50 parts by weight of the addition product of 7 mol of
ethylene oxide to 1 mol of isooctylphenol and 50 parts by weight of
the addition product of 40 mol of ethylene oxide to 1 mol of castor
oil). The stock solution is then diluted to the desired
concentration by dispersion in water, for example to a
concentration in the range from 1 to 100 ppm.
[0132] The active compounds can be applied as such, in the form of
their formulations or in the application forms prepared therefrom,
for example in the form of directly sprayable solutions, powders,
suspensions or dispersions, emulsions, oil dispersions, pastes,
dusts, compositions for broadcasting, or granules, by spraying,
atomizing, dusting, broadcasting or watering. The application forms
depend entirely on the intended uses; in any case, they should
ensure very fine dispersion of the active compounds according to
the invention.
[0133] Aqueous use forms can be prepared from emulsion
concentrates, pastes or wettable powders (spray powders, oil
dispersions) by addition of water. To prepare emulsions, pastes or
oil dispersions, the substances can be homogenized in water as such
or dissolved in an oil or solvent, by means of wetting agents,
tackifiers, dispersants or emulsifiers. However, concentrates
comprising active compound, wetting agent, tackifier, dispersant or
emulsifier and possibly solvent or oil which are suitable for
dilution with water can also be prepared.
[0134] The active compound concentrations in the ready-to-use
preparations can be varied over a relatively wide range. In
general, they are from 0.0001 to 10%. Frequently, even low amounts
of the active compound I in the ready-to-use preparation are
sufficient, for example 2 to 200 ppm. Preference is also given to
ready-to-use preparations having active compound concentrations in
the range from 0.01 to 1%.
[0135] It is also possible to use the active compounds with a high
degree of success in the ultra-low-volume method (ULV), it being
possible to apply formulations comprising more than 95% by weight
of active compound or even the active compound without
additives.
[0136] Oils of various types, herbicides, fungicides, other
pesticides and bactericides can be added to the active compounds,
if desired even immediately prior to application (tank mix). These
agents can be added to the compositions according to the invention
in a weight ratio of 1:10 to 10:1.
[0137] The compositions according to the invention in the use form
as fungicides may also be present in combination with other active
compounds, for example with herbicides, insecticides, growth
regulators, fungicides or else with fertilizers. In many cases, a
mixture of the compounds I, or of the compositions comprising them,
in the use form as fungicides with other fungicides results in a
broader fungicidal spectrum of activity.
[0138] The following list of fungicides in combination with which
the compounds according to the invention can be used is intended to
illustrate the possible combinations, but not to impose any
limitation: [0139] sulfur, dithiocarbamates and their derivatives,
such as iron(III) dimethyldithiocarbamate, zinc
dimethyldithiocarbamate, zinc ethylenebisdithiocarbamate, manganese
ethylenebisdithiocarbamate, manganese zinc
ethylenediaminebisdithiocarbamate, tetramethylthiuram disulfide,
ammonia complex of zinc (N,N-ethylenebisdithiocarbamate), ammonia
complex of zinc (N,N'-propylenebisdithiocarbamate), zinc
(N,N'-propylenebisdithiocarbamate),
N,N'-polypropylenebis(thiocarbamoyl)disulfide; [0140] nitro
derivatives, such as dinitro-(1-methylheptyl)phenyl crotonate,
2-sec-butyl-4,6-dinitrophenyl-3,3-dimethyl acrylate,
2-sec-butyl-4,6-dinitrophenylisopropyl carbonate, diisopropyl
5-nitroisophthalate; [0141] heterocyclic substances, such as
2-heptadecyl-2-imidazoline acetate,
2-chloro-N-(4'-chlorobiphenyl-2-yl)nicotinamide,
2,4-dichloro-6-(o-chloroanilino)-s-triazine, 0,0-diethyl
phthalimidophosphonothioate,
5-amino-1-[bis(dimethylamino)phosphinyl]-3-phenyl-1,2,4-triazole,
2,3-dicyano-1,4-dithioanthraquinone,
2-thio-1,3-dithiolo[4,5-b]quinoxaline, methyl
1-(butylcarbamoyl)-2-benzimidazolecarbamate,
2-methoxycarbonylaminobenzimidazole, 2-(fur-2-yl)benzimidazole,
2-(thiazol-4-yl)benzimidazole, [0142]
N-(1,1,2,2-tetrachloroethylthio)tetrahydrophthalimide,
N-trichloromethylthiotetrahydrophthalimide,
N-trichloromethylthiophthalimide, [0143]
N-dichlorofluoromethylthio-N',N'-dimethyl-N-phenylsulfuric diamide,
5-ethoxy-3-trichloromethyl-1,2,3-thiadiazole,
2-thiocyanatomethylthiobenzothiazole,
1,4-dichloro-2,5-dimethoxybenzene,
4-(2-chlorophenylhydrazono)-3-methyl-5-isoxazolone, pyridine
2-thio-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-carboxanilide, 2,5-dinethylfuran-3-carboxanilide,
2,4,5-trimethylfuran-3-carboxanilide,
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-1-(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-cyclododecylmorpholine or its salts,
N-[3-(p-tert-butylphenyl)-2-methylpropyl]-cis-2,6-dimethylmorpholine,
N-[3-(p-tert-butylphenyl)-2-methyl- propyl]piperidine,
1-[2-(2,4-dichlorophenyl)-4-ethyl-1,3-di-
oxolan-2-ylethyl]-lH-1,2,4-triazole, 1-[2-(2,4-dichloro-
phenyl)-4-n-propyl-1,3-dioxolan-2-ylethyl]-lH-1,2,4-triazole,
N-(n-propyl)-N-(2,4,6-trichlorophenoxyethyl)-N'-imidazolylurea,
1-(4-chlorophenoxy)-3,3-dimethyl-1-(lH-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-chloro-
phenyl)-2-(4-fluorophenyl)oxiran-2-ylmethyl)-lH-1,2,4- triazole,
.alpha.-(2-chlorophenyl)-.alpha.-(4-chlorophenyl)-5-pyrimidine-methanol
5-butyl-2-dimethylamino-4-hydroxy-6-methylpyrimidine, bis
(p-chlorophenyl) -3-pyridinemet-hanol,
1,2-bis(3-ethoxycarbbnyl-2-thioureido)benzene,
1,2-bis(3-methoxycarbonyl-2-thioureido)benzene, [0144]
strobilurins, such as methyl E-methoxyimino-([.alpha.-(o-tolyloxy)-
o-tolyllacetate, methyl E-2-{2-16-(2-cyanophenoxy)-
pyridimin-4-yloxy]phenyl}-3-methoxyacrylate, methyl
E-methoxyimino-[.alpha.-(2-phenoxyphenyl)]acetamide, methyl
E-methoxyimino-[.alpha.-(2,5-dimethylphenoxy)-o-tolyl]acetamide,
methyl E-2-{2-[(2-trifluoromethylpyrid-6-yl)oxymethyl]phenyl}-3-
methoxyacrylate, methyl
(E,E)-methoximino-{2-[l-(3-trifluoromethylphenyl)ethylidene-
aminooxymethyl]phenyl}acetate, methyl
N-(2-{[1-(4-chlorophenyl)-lH-pyrazol-3-yl.]oxymethyl}phenyl)-N-methoxycar-
bamate, [0145] anilinopyrimidines, such as
N-(4,6-dimethylpyrimidin-2- yl)aniline,
N-[4-methyl-6-(1-propynyl)pyrimidin-2-yl]aniline, N- (
4-methyl-6-cyclopropylpyrimidin-2-yl) aniline, [0146]
phenylpyrroles, such as 4-(2,2-difluoro-1,3-benzodioxol-4-
yl)pyrrole-3-carbonitrile, [0147] cinnamamides, such as
3-(4-chlorophenyl)-3-(3,4-dimethoxy- phenyl)acryloylmorpholide,
3-(4-fluorophenyl)-3-(3,4- dimethoxyphenyl)acryloylmorpholide,
[0148] and a variety of fungicides, such as dodecylguanidine
acetate,
1-(3-bromo-6-methoxy-2-methylphenyl)-1-(2,3,4-trimethoxy-6-
methylphenyl)methanone,
3-[3-(3,5-dimethyl-2-oxycyclohexyl)-2-hydroxyethyl]glutarimide,
hexachlorobenzene, methyl N-(2,6-dimethylphenyl)-N-
(2-furoyl)-DL-alaninate, 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-methoxy-
methyl-1,3-oxazolidine-2,4-dione, 3-(3,5-dichloro-
phenyl)-1-isopropylcarbamoylhydantoin, N-( 3,5-dichloro-
phenyl)-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-a-(lH-1,2,4-triazolyl-1-methyl)benzohydryl alcohol,
N-(3-chloro-2,6-dinitro-4-trifluoromethylphenyl)-
5-trifluoromethyl-3-chloro-2-aminopyridine, 1-((bis(4-
fluorophenyl)methylsilyl)methyl)-lH-1,2,4-triazole,
N,N-dimethyl-5-chloro-2-cyano-4-p-tolylimidazole-l-sulfonamide,
3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methyl
benzamide. Synthesis of the Precursor
Preparation of (R)-3,3-dimethylbut-2-ylamine (the synthesis was
carried out according to Scheme 1 on page 6 of the description)
[0148] a) Resolution of the Racemate
[0149] 280 g (2.75 mol) of racemic 3,3-dimethylbut-2-ylamine were
initially charged, cooled to about 15.degree. C. and mixed with 187
g (1.42 mol) of isopropyl methoxy acetate. 3 g of Novozym.RTM. 435
(=lipase from Candida antarctica) were then added, and the mixture
was stirred at 25-30.degree. C. for 2 days. The optical purity of
the (S)-3,3-dimethylbut-2-ylamine (S-DMBA) was then 97% ee and that
of the N-(3,3-dimethylbut-2-yl)-.alpha.-methoxyacetamide
(R-DMBamide) formed was 99.3% ee (conversion: 49.4 %). The catalyst
was filtered off with suction and washed twice with in each case 30
ml of isopropanol. The combined filtrates were separated
distillatively using a thin-film evaporator. At a top pressure of
50 mbar and a mantel temperature of 140.degree. C., a mixture of
isopropanol and S-DMBA having a boiling point of 45.degree. C.
distilled off via the top. The less volatile bottom consisted of
R-DMBamide and unreacted acylating agent, isopropyl methoxyacetate.
This less volatile mixture was once more charged using the
thin-film evaporator. This time, the mantel temperature was
adjusted to 140.degree. C. and the top pressure to 35 mbar. At
60.degree. C., the unreacted acylating agent, isopropyl methoxy
acetate, distilled off via the top. The less volatile bottom
consisted of pure R-DMBamide (ee: 99.3%), yield 249 g (94%).
[0150] b) Amide Cleavage and Pure Distillation: 190 g (1.1 mol) of
R-DMBamide were diluted with 100 g of triethanolamine and, with
stirring, heated at 120.degree. C. At this temperature, 150 g of
50% strength aqueous sodium hydroxide solution and then 100 g of
water were introduced over a period of 2 hours. The
(R)-3,3-dimethylbut-2-ylamine (R-DMBA) formed distilled off
azeotropically with water (top temperature: 84-86.degree. C.). The
reflux was led through a phase separator, and the aqueous amine,
which separated off as upper phase, was discharged. The lower phase
(water) was recycled into the reaction flask. The mixture was
boiled until the top temperature had remained above 95.degree. C.
for 6 hours. The aqueous amine that had been separated off (water
content: 45%) was mixed with 100 ml of n-hexane, and the mixture
was heated to reflux. At a top temperature of 61.degree. C., a
heteroazeotrope consisting of n-hexane and water distilled off. At
total reflux the azeotrope was led through a phase separator and
the aqueous lower phase was separated off. The upper phase was
returned to the distillation flask. Once all the water had been
removed azeotropically, the top temperature increased to 69.degree.
C. using a reflux/discharge ratio of 5:1, the entrainer n-hexane
was distilled off. When the temperature had reached 71.degree. C.,
the reflux/discharge ratio was increased to 10:1, and an
intermediate fraction was collected up to a top temperature of
103.degree. C. The pure product distilled at 103.degree. C. This
gave 105 g (99%) of the product as a colorless liquid.
[0151] .sup.1H-NMR (360 MHz, CDC1.sub.3): 0.85 ppm (s, 9 H), 1.00
ppm (d, J =7 Hz, 3 H), 1.25 ppm (s, wide, 2H), 2.60 ppm (q, J =7
Hz, 1 H).
Preparation of 5,7-dihydroxy-6-(2,4,6-trifluorophenyl)-l,2,4-
triazolo[1,5-a]pyrimidine
[0152] A mixture of 22 mmol of diethyl
2-(2,4,6-trifluorophenyl)malonate, 24 mmol of triethylamine and 22
mmol of 3-amino-1,2,4-triazole was heated with stirring at
180.degree. C. for 6 hours. The reaction mixture was then cooled to
50.degree. C., admixed with a solution of 2.2 g of sodium hydroxide
in 25 ml of water and stirred for 30 minutes. The aqueous phase was
washed with ether and then acidified with conc. hydrochloric acid.
The precipitated colorless solid was filtered off, washed with
water and diisopropyl ether and dried. The yield of the title
compound was 85% (m.p.: 200-201.degree. C.).
Preparation of
5,7-dichloro-6-(2,4,6-trifluorophenyl)-1,2,4-triazolo[1,5-a]-pyrimidine
[0153] 16 mmol of
5,7-dihydroxy-6-(2,4,6-trifluorophenyl)-1,2,4-triazolo[1,5-a]-
pyrimidine in 20 ml of phosphorus oxychloride were heated to the
boil for 4 hours. Excess phosphorus oxychloride was distilled off.
The distillation residue was cooled to room temperature and admixed
with 100 ml of dichloromethane. 125 ml of water were then added at
a temperature below 40.degree. C. The organic phase was dried over
sodium sulfate and the solvent was then distilled off. A colorless
solid remained in the reaction vessel, with a yield of 72% (m.p.:
125-126.degree. C.).
Synthesis of the Active Compounds
[0154] The procedures shown in the Synthesis Examples below were,
with appropriate modification of the starting materials, used to
obtain further compounds I. The resulting compounds are listed in
the tables below, together with physical data.
EXAMPLE 1
Preparation of
(R)-5-chloro-7-(3,3-dimethylbut-2-yl)amino-6-(2,4,6-trifluoro-
phenyl)-1,2,4-triazolo[1,5-a]pyrimidine
[0155] With stirring, a mixture of 1.4 mmol of
(R)-3,3-dimethylbut-2-ylamine, 1.4 mmol of triethylamine and 10 ml
of dichloromethane was introduced into a mixture of 1.4 mmol of
5,7-dichloro-6-(2,4,6-trifluorophenyl)-1,2,4-triazolo[1,5-a]-
pyrimidine in 30 ml of dichloromethane. The reaction mixture was
then stirred at room temperature for 16 hours and finally washed
with 1 N hydrochloric acid and water. The organic phase was dried
over anhydrous sodium sulfate. The solvent was distilled off under
reduced pressure. The crude product was purified by silica gel
column chromatography. This gave the title compound in the form of
colorless crystals in a yield of 76% (m.p.: 169-171.degree. C.).
TABLE-US-00002 TABLE A IA ##STR7## Phys. data No. R.sup.1 R.sup.3
(R.sup.4).sub.n (m.p. [.degree. C.]) 1-1 H CH.sub.2CH.sub.3
2-Cl-6-F 147 1-2 H CH(CH.sub.3).sub.2 2-Cl-6-F 145 1-3 H
C(CH.sub.3).sub.3 2-Cl-6-F 191 1-4 H CH.sub.2CH.sub.3 2,6-F.sub.2
176 1-5 H CH(CH.sub.3).sub.2 2,6-F.sub.2 149 1-6 H
C(CH.sub.3).sub.3 2,6-F.sub.2 175 1-7 H CH.sub.2CH.sub.3
2,6-Cl.sub.2 123 1-8 H CH(CH.sub.3).sub.2 2,6-Cl.sub.2 132 1-9 H
C(CH.sub.3).sub.3 2,6-Cl.sub.2 216 1-10 H CH.sub.2CH.sub.3
2-CH.sub.3-6-F 123 1-11 H CH(CH.sub.3).sub.2 2-CH.sub.3-6-F 116/132
1-12 H C(CH.sub.3).sub.3 2-CH.sub.3-6-F 158/203 1-13 H
CH.sub.2CH.sub.3 2,4,6-F.sub.3 87 1-14 H CH(CH.sub.3).sub.2
2,4,6-F.sub.3 87 1-15 H C(CH.sub.3).sub.3 2,4,6-F.sub.3 170 1-16 H
CH.sub.2CH.sub.3 2,6-F2-4-OCH.sub.3 129 1-17 H CH(CH.sub.3).sub.2
2,6-F2-4-OCH.sub.3 141 1-18 H C(CH.sub.3).sub.3 2,6-F2-4-OCH.sub.3
186 1-19 H CH.sub.2CH.sub.3 F5 99 1-20 H CH(CH.sub.3).sub.2 F5 152
1-21 H C(CH.sub.3).sub.3 F5 109 1-22 H CH.sub.2CH.sub.3
2-CH.sub.3-4-F 124 1-23 H CH(CH.sub.3).sub.2 2-CH.sub.3-4-F 123
1-24 H C(CH.sub.3).sub.3 2-CH.sub.3-4-F 154 1-25 H
CH(CH.sub.3).sub.2 2-CF.sub.3 154 1-26 H C(CH.sub.3).sub.3
2-CF.sub.3 142 1-27 H (CH.sub.2).sub.3CH.sub.3 2,4,6-F.sub.3 91
1-28 H (CH.sub.2).sub.4CH.sub.3 2,4,6-F.sub.3 189 1-29 H
(CH.sub.2).sub.5CH.sub.3 2,4,6-F.sub.3 169 I-JO H
(CH.sub.2).sub.6CH.sub.3 2,4,6-F.sub.3 175 1-31 H cyclohexyl
2,4,6-F.sub.3 145 1-32 H CH.sub.2OCH.sub.3 2,4,6-F.sub.3 97 1-33 H
CH.sub.2CH.sub.3 2-CH.sub.3-4-Cl 114 1-34 H CH(CH.sub.3).sub.2
2-CH.sub.3-4-Cl 130 1-35 H C(CH.sub.3).sub.3 2-CH.sub.3-4-Cl 159
1-36 H CH.sub.2CH.sub.3 2-F-4-CH.sub.3 1-37 H CH(CH.sub.3).sub.2
2-F-4-CH.sub.3 1-38 H C(CH.sub.3).sub.3 2-F-4-CH.sub.3 1-39 H
CH.sub.2CH.sub.3 2-F-6-OCH.sub.3 1-40 H CH(CH.sub.3).sub.2
2-F-6-OCH.sub.3 1-41 H C(CH.sub.3).sub.3 2-F-6-OCH.sub.3 1-42 H
CH.sub.2CH.sub.3 2-Cl 110 1-43 H CH(CH.sub.3).sub.2 2-Cl 95/112
1-44 H C(CH.sub.3).sub.3 2-Cl 152/196
[0156] Owing to the chiral 7-amino group and the hindered rotation
of the 6-phenyl group, in the case of unsymmetrical phenyl
substitution, there are in each case two diastereomers which may
differ in their physical properties.
USE EXAMPLES
Examples of the Activity Against Harmful Fungi
[0157] The fungicidal action of the compounds of the formula I was
demonstrated by the following experiments:
[0158] The active compounds were prepared separately or jointly as
a 10% strength emulsion in a mixture of 70% by weight of
cyclohexanone, 20% by weight of Nekanil.RTM. LN (Lutensol.RTM. AP6,
wetting agent having emulsifying and dispersing action based on
ethoxylated alkylphenols) and 10% by weight of Wettol.RTM. EM
(nonionic emulsifier based on ethoxylated castor oil) and diluted
with water to the desired concentration.
General Remarks for Use Examples 1 to 4
[0159] In WO-A 98/46607, some of the compounds listed below are
described as racemates. Furthermore, on page 7, paragraphs 1 and 2,
it is emphasized that, in particular with respect to compounds
having a haloalkylamine substitution in the 7-position, preference
is given to the S enantiomers. The present compounds have a
non-halogenated alkylamine moiety in the 7-position. Analogously,
here too, an increased efficacy of the S enantiomers was to be
expected. In the experiments below, the R enantiomer and the S
enantiomer are in each case compared.
USE EXAMPLE 1 :
Curative activity against brown rust of wheat caused by Puccinia
recondita
[0160] Leaves of potted wheat seedlings of the cultivar "Kanzler"
were dusted with spores of brown rust (Puccinia recondita). The
pots were then placed in a chamber with high atmospheric humidity
(90 to 95%) at 20-22.degree. C. for 24 hours. During this period,
the spores germinated and the germinal tubes penetrated into the
leaf tissue. The following day, the infected plants were sprayed to
runoff point with an aqueous preparation of active compound which
had been prepared from a stock solution made of 10% of active
compound, 85% of cyclohexanone and 5% of emulsifier. After the
spray coating had dried on, the test plants were cultivated in a
greenhouse at 20-22.degree. C. and 65-70% relative atmospheric
humidity for 7 days. The extent of the rust fungus development on
the leaves was then determined. TABLE-US-00003 % infection of the
leaves after application of an aqueous preparation comprising . . .
Active compound ppm of active compound of Table I 250 63 16 ppm No.
I.-1 (R)-amine 0 3 5 comparison (S)-amine 15 20 60 No. I.-2
(R)-amine 5 5 15 comparison (S)-amine 100 100 100 I.-3 (R)-amine 20
/ / comparison (S)-amine 100 / / No. I.-4 (R)-amine 10 20 40
comparison (S)-amine 100 100 100 No. I.-5 (R)-amine 10 10 /
comparison (S)-amine 100 100 / No. I.-7 (R)-amine / / 40 comparison
(S)-amine / / 100 No. I.-10 (R)-amine 15 40 60 comparison (S)-amine
100 100 100 No. I.-11a (R)-amine 5 5 80 comparison (S)-amine 30 60
100 No. I.-11b (R)-amine 5 20 / comparison (S)-amine 100 100 / No.
I.-13 (R)-amine / 0 3 comparison (S)-amine / 3 60 No. I.-14
(R)-amine / 0 0 comparison (S)-amine / 5 100 No. I.-15 (R)-amine 0
0 0 comparison (S)-amine 100 100 100 No. I.-16 (R)-amine / 0 7
comparison (S)-amine / 5 100 No. I.-22 (R)-amine 3 5 30 comparison
(S)-amine 100 100 100 No. I.-23 (R)-amine 0 0 3 comparison
(S)-amine 100 100 100 No. I.-27 (R)-amine 40 / / comparison
(S)-amine 100 / / No. I.-32 (R)-amine 15 70 / comparison (S)-amine
80 100 / No. I.-42 (R)-amine 5 20 30 comparison (S)-amine 15 60 100
No. I.-44a (R)-amine 60 / / comparison (S)-amine 100 / / untreated
100
USE EXAMPLE 2:
Activity against net blotch of barley caused by Pyrenophora
teres
[0161] Leaves of potted barley seedlings of the cultivar "Igri"
were sprayed to runoff point with an aqueous preparation of active
compound which had been prepared from a stock solution made of 10%
of active compound, 85% of cyclohexanone and 5% of emulsifier and
were inoculated 24 hours after the- spray coating had dried on with
an aqueous spore suspension of Pyrenophora teres, the net blotch
pathogen. The test plants were then placed in a greenhouse at
20-24.degree. C. and 95-100% relative atmospheric humidity. After 6
days, the extent of the development of the disease was determined
visually in % infection of the entire leaf area. TABLE-US-00004 %
infection of the leaves after application of an aqueous preparation
comprising . . . Active compound ppm of active compound of Table I
250 63 16 ppm No. I.-1 (R)-amine / 0 50 comparison (S)-amine / 20
100 No. I.-5 (R)-amine / / 20 comparison (S)-amine / / 80 No. I.-6
(R)-amine / 0 0 comparison (S)-amine / 5 60 No. I.-7 (R)-amine 15
30 80 comparison (S)-amine 100 100 100 No. I.-8 (R)-amine 15 15 40
comparison (S)-amine 100 100 100 No. I.-9 (R)-amine 0 0 0
comparison (S)-amine 100 100 100 No. I.-10 (R)-amine 3 3 /
comparison (S)-amine 40 100 / No. I.-11a (R)-amine 0 0 5 comparison
(S)-amine 100 100 100 No. I.-11b (R)-amine 0 15 / comparison
(S)-amine 100 100 / No. I.-12a (R)-amine 0 0 0 comparison (S)-amine
100 100 100 No. I.-12b (R)-amine 0 7 7 comparison (S)-amine 100 100
100 No. I.-13 (R)-amine / / 20 comparison (S)-amine / / 60 No.
I.-14 (R)-amine / / 3 comparison (S)-amine / / 40 No. I.-19
(R)-amine 30 / / comparison (S)-amine 80 / / No. I.-20 (R)-amine 0
10 30 comparison (S)-amine 7 40 100 No. I.-22 (R)-amine / 0 7
comparison (S)-amine / 7 80 No. I.-23 (R)-amine / / 0 comparison
(S)-amine / / 60 No. I.-27 (R)-amine 0 0 3 comparison (S)-amine 7
90 100 No. I.-28 (R)-amine 20 40 90 comparison (S)-amine 100 100
100 No. I.-31 (R)-amine 0 3 40 comparison (S)-amine 80 80 100 No.
I.-32 (R)-amine 0 0 5 comparison (S)-amine 30 80 90 No. I.-44a
(R)-amine / 7 60 comparison (S)-amine / 30 100 untreated 100
USE EXAMPLE 3:
Protective activity against Septoria foliar blotch disease of wheat
caused by Septoria tritici
[0162] Leaves of potted wheat seedlings of the cultivar "Riband"
were sprayed to runoff point with an aqueous preparation of active
compound which had been prepared from a stock solution made of 10%
of active compound, 85% of cyclohexanone and 5% of emulsifier. 24
hours after the spray coating had dried on, they were inoculated
with an aqueous spore suspension of Septoria tritici. The
suspension contained 2.0 .times.106 spores/ml. The test plants were
then placed in a greenhouse at 18-22.degree. C. and a relative
atmospheric humidity of close to 100%. After 2 weeks, the extent of
the development of the disease was determined visually in %
infection of the entire leaf area. TABLE-US-00005 % infection of
the leaves after application of an aqueous preparation comprising .
. . Active compound ppm of active compound of Table I 250 63 16 ppm
No. I.-2 (R)-amine 0 0 0 comparison (S)-amine 90 90 90 No. I.-4
(R)-amine 3 15 20 comparison (S)-amine 90 100 100 No. I.-5
(R)-amine 15 15 15 comparison (S)-amine 100 100 100 No. I.-7
(R)-amine 15 30 70 comparison (S)-amine 90 90 90 No. I.-8 (R)-amine
30 30 70 comparison (S)-amine 90 90 90 No. I.-14 (R)-amine 15 15 15
comparison (S)-amine 70 70 90 No. I.-16 (R)-amine 70 70 /
comparison (S)-amine 90 90 / No. I.-17 (R)-amine 10 10 10
comparison (S)-amine 90 90 90 No. I.-18 (R)-amine 30 / / comparison
(S)-amine 80 / / No. I.-19 (R)-amine 10 10 50 comparison (S)-amine
90 90 90 No. I.-20 (R)-amine 10 10 10 comparison (S)-amine 90 90 90
No. I.-25 (R)-amine 0 0 0 comparison (S)-amine 100 100 100 No.
I.-26 (R)-amine 0 0 3 comparison (S)-amine 100 100 100 No. I.-44a
(R)-amine 7 7 60 comparison (S)-amine 100 100 100 No. I.-44b
(R)-amine 10 10 30 comparison (S)-amine 80 80 80 untreated 100
USE EXAMPLE 4:
Activity against mildew of wheat caused by Blumeria graminis forma
specialis tritici
[0163] Leaves of potted wheat seedlings of the cultivar "Kanzler"
were sprayed to runoff point with an aqueous preparation of active
compound which had been prepared from a stock solution made of 10%
of active compound, 85% of cyclohexanone and 5% of emulsifier and
were dusted 24 hours after the spray coating had dried on with
spores of mildew of wheat (Blumeria graminis forma specialis
tritici). The test plants were then placed in a greenhouse at
20-24.degree. C. and 60-90% relative atmospheric humidity. After 7
days, the extent of the mildew development was determined visually
in % infection of the entire leaf area. TABLE-US-00006 % infection
of the leaves after application of an aqueous preparation
comprising . . . Active compound ppm of active compound of Table I
250 63 16 ppm No. I.-2 (R)-amine 40 40 / comparison (S)-amine 100
100 / No. I.-4 (R)-amine 60 60 80 comparison (S)-amine 100 100 100
No. I.-5 (R)-amine 20 40 40 comparison (S)-amine 100 100 100 No.
I.-6 (R)-amine 40 50 / comparison (S)-amine 90 90 / No. I.-7
(R)-amine 60 / / comparison (S)-amine 100 / / No. I.-10 (R)-amine
15 60 / comparison (S)-amine 100 100 / No. I.-11a (R)-amine 5 7 7
comparison (S)-amine 60 60 80 No. I.-11b (R)-amine 30 30 /
comparison (S)-amine 60 60 / No. I.-12a (R)-amine 7 7 7 comparison
(S)-amine 100 100 100 No. I.-12b (R)-amine 60 60 60 comparison
(S)-amine 100 100 100 No. I.-13 (R)-amine / 40 60 comparison
(S)-amine / 60 100 No. I.-14 (R)-amine 20 30 30 comparison
(S)-amine 80 80 100 No. I.-15 (R)-amine 3 7 7 comparison (S)-amine
40 80 90 No. I.-16 (R)-amine 20 40 40 comparison (S)-amine 100 100
100 No. I.-17 (R)-amine 60 60 60 comparison (S)-amine 100 100 100
No. I.-19 (R)-amine 7 7 / comparison (S)-amine 30 30 / No. I.-20
(R)-amine 5 20 30 comparison (S)-amine 40 40 80 No. I.-22 (R)-amine
3 3 5 comparison (S)-amine 70 70 80 No. I.-23 (R)-amine 3 5 15
comparison (S)-amine 40 60 60 No. I.-24 (R)-amine 3 5 10 comparison
(S)-amine 15 60 60 No. I.-31 (R)-amine 5 7 15 comparison (S)-amine
15 50 50 No. I.-44a (R)-amine 30 30 50 comparison (S)-amine 100 100
100 untreated 100
[0164] In the above experiments, in all cases the R enantiomer
shows considerably better activity than the S enantiomer.
* * * * *