CA2032682A1 - Pesticidal compositions - Google Patents
Pesticidal compositionsInfo
- Publication number
- CA2032682A1 CA2032682A1 CA002032682A CA2032682A CA2032682A1 CA 2032682 A1 CA2032682 A1 CA 2032682A1 CA 002032682 A CA002032682 A CA 002032682A CA 2032682 A CA2032682 A CA 2032682A CA 2032682 A1 CA2032682 A1 CA 2032682A1
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- compounds
- c4alkyl
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- unsubstituted
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
PS/5- 17887/1+2/=
Pesticidal compositions Abstract Thiazolyl-5-carbonamide derivatives of formula I
Pesticidal compositions Abstract Thiazolyl-5-carbonamide derivatives of formula I
Description
20326~3~
, PS/s-l7887/l+2!=
Pesticidal compositions The present invention relates to novel thiazolyl-S-carbonamide derivatives of forrnula I
below. The invention relates also to the preparation of those compounds and to agro-chemical compositions that contain at least one of those compounds as active ingredient.
The invention relates also to the preparation of the said compositions and to the use of the compounds or the compositions for controlling microorganisms, especially plant-destructive microorganisms, particularly fungi.
The compounds according to the invention correspond to the general formula I and include the acid addition salts and metal salt complexes thereof.
R~ ,¢ CO--NH--CH--R3 (I) In this formula:
R3 is 2-furanyl, 2-thienyl, 3-furanyl or 3-thienyl;
R1 and R2 are each independently of the other a) C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio,b) the group -CH2-X-R4, and c) one of the two substituents Rl and R2 may also be hydrogen or Cl-C4alkyl, wherein X is oxygen or sulfur, and R4 is Cl-C4alkyl that may be unsubstituted or substituted by halogen or, in the case of C2-C4alkyl, also by Cl-C3alkoxy, or wherein R4 is C3-C4alkenyl, C3-C4alkynyl or a phenyl group or benzyl group of which the aromatic ring is unsubstituted or may be substituted by halogen, Cl-C2alkyl, Cl-C2alkoxy, CF3 or by NO2.
Depending upon the number of carbon atoms indicated, alkyl by itself or as a constituent of another substituent, such as haloalkyl or alkoxy, is to be understood as being, for example, methyl, ethyl, propyl, butyl, and the isomers isopropyl, isobutyl, tert.-butyl or ~ ' :
. .
203~;8~
, PS/s-l7887/l+2!=
Pesticidal compositions The present invention relates to novel thiazolyl-S-carbonamide derivatives of forrnula I
below. The invention relates also to the preparation of those compounds and to agro-chemical compositions that contain at least one of those compounds as active ingredient.
The invention relates also to the preparation of the said compositions and to the use of the compounds or the compositions for controlling microorganisms, especially plant-destructive microorganisms, particularly fungi.
The compounds according to the invention correspond to the general formula I and include the acid addition salts and metal salt complexes thereof.
R~ ,¢ CO--NH--CH--R3 (I) In this formula:
R3 is 2-furanyl, 2-thienyl, 3-furanyl or 3-thienyl;
R1 and R2 are each independently of the other a) C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio,b) the group -CH2-X-R4, and c) one of the two substituents Rl and R2 may also be hydrogen or Cl-C4alkyl, wherein X is oxygen or sulfur, and R4 is Cl-C4alkyl that may be unsubstituted or substituted by halogen or, in the case of C2-C4alkyl, also by Cl-C3alkoxy, or wherein R4 is C3-C4alkenyl, C3-C4alkynyl or a phenyl group or benzyl group of which the aromatic ring is unsubstituted or may be substituted by halogen, Cl-C2alkyl, Cl-C2alkoxy, CF3 or by NO2.
Depending upon the number of carbon atoms indicated, alkyl by itself or as a constituent of another substituent, such as haloalkyl or alkoxy, is to be understood as being, for example, methyl, ethyl, propyl, butyl, and the isomers isopropyl, isobutyl, tert.-butyl or ~ ' :
. .
203~;8~
sec.-butyl. Halogen, also referred to as Hal, is fluorine, chlorine, bromine or iodine.
Haloalkyl indicates mono- to per-halogenated radicals, for example CHCl2, CH2F, CCI3, CH2CI, CHF2, CF3, CH2C~2Br, C2CI5, C~12Br, CHBrCI etc.. Depending upon the number of carbon atoms indicated, cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
The compounds of formula I are oils or solids that are stable at room temperature and are distinguished by valuable microbicidal properlies. They can be used preventively and curatively in the agricultural sector or related fields for controlling plant-destructive microorganisms. The compounds of formula I according to the invention are, when used in low concentrations, distinguished not only by excellent microbicidal, especially fungi-cidal, activity but also by especially good plant tolerability.
The compounds of formula 1 have an asymmetric carbon atom adjacent to the nitrile group. They can therefore be cleaved into optical antipodes in customary manner. These antipodes have different microbicidal actions.
The invention relates both to the free compounds of formula I and to the addition salts thereof with inorganic and organic acids and the complexes thereof with metal salts.
Salts according to the invention are especially addition salts with acceptable inorganic or organic acids, for example hydrohalic acids, for example hydrochloric, hydrobromic or hydriodic acid, sulfuric acid, phosphoric acid, phosphorous acid, nitric acid, or organic acids such as acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, glycolic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid, oxalic acid, formic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, salicylic acid, p-aminosalicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid or 1,2-naphthalenedisulfonic acid.
Metal salt complexes of forrnula I consist of the underlying organic molecule and an inorganic or organic metal salt, for example the halides, nitrates, sulfates, phosphates, acetates, trifluoroacetates, trichloroacetates, propionates, tartrates, sulfonates, salicylates, benzoates etc. of the elements of main group II, such as calcium and magnesium, and main groups III and IV, such as aluminium, tin or lead, and of subgroups I to Vlll, such as chromium, manganese, iron, cobalt, nickel, copper, zinc, etc.. Subgroup elements of the 4th period are preferred. The metals can be present in any of the various valencies 3 203268~
attributed to them. The metal complexes may be mono- or poly-nuclear, that is to say they may contain one or more organic molecule components as ligands.
An important group of phytofungicides and insecticides comprises those of formula I
wherein one of the two subsdtuents Rl and R2 is C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio, and the other substituent is d) cyclobutyl, cyclopropyl, methylcyclopropyl or methylthiocyclopropyl, e) the group -CH2-X-R4 or f) hydrogen or Cl-C4alkyl, while R3, X and R4 are as defined above.
Here and hereinbelow this group is referred to as compound group IA.
Among the compounds of group IA, special mention should be made of those wherein one of the two substituents Rl and R2 is C3-C6cycloalkyl and the other is cyclobutyl or cyclo-propyl, while R3 is as defined above (group IAA), and of those, in turn, those compounds wherein Rl and R2 are cyclopropyl.
Important compounds are also those of group IA wherein Rl is C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio, R2 is hydrogen, Cl-C4alkyl or the group -CH2-X-R4, X is oxygen or sulfur, and R4 is Cl-C4alkyl that is unsubstituted or substituted by fluorine or, in the case of C2-C4alkyl, may also be substituted by Cl-C3alkoxy; or wherein R4 is allyl, propargyl, phenyl or benzyl, the aromatic rings of the latter radicals being unsubstituted or substituted by one or two of the substituents fluorine, chlorine, methyl, ethyl, methoxy and CF3, while R3 is as defined above (group IB).
Those compounds of group IB wherein X is oxygen are preferred (group IBB).
Important compounds within group IBB are those wherein Rl is cyclobutyl, cyclopropyl, methylcyclopropyl or methylthiocyclopropyl, R2 is hydrogen, Cl-C4alkyl or -CH2-O-R4, wherein R4 is C1-C4alkyl that is unsubstituted or substituted by fluorine, methoxy or by ethoxy, or - : ~ . ..
:: .
.. . - ~.
:
Z0326?3 wherein R4 is allyl, propargyl, phenyl, chlorophenyl, fluorophenyl, benzyl, chloro-benzyl or fluorobenzyl (= subgroup Ib).
Preferred compounds within group Ib are those wherein Rl is cyclopropyl, R2 is hydrogen, Cl-C4alkyl or -CH2-O-R4, wherein R4 is methyl, ethyl, fluoromethyl, difluoromethyl, trifluoroethyl, allyl, propargyl, phenyl or benzyl, while R3 is as defined above (= subgroup Ibb).
Especially preferred compounds within group Ibb are those wherein R2 is hydrogen, C~-C3alkyl, methoxymethyl or ethoxymethyl.
Important compounds are also those of group la wherein Rl is hydrogen, Cl-C4alkyl or the group -CH2-X-R4, X is oxygen or sulfur, and R4 is Cl-C4alkyl that is unsubstituted or substituted by fluorine or, in the case of C2-C4alkyl, may also be substituted by Cl-C3alkoxy; or wherein R4 is a!lyl, propargyl, phenyl or benzyl, the aromatic rings of the latter radicals being unsubstituted or substituted by one or two of the substituents fluorine, chlorine, methyl, ethyl, methoxy and CF3, while R2 is C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio, while R3 is as defined above (= group IC), especially those wherein X is oxygen (= group ICC).
Within that group ICC, preferred compounds are those wherein Rl is hydrogen, Cl-C4alkyl r-CH2-O-R4-R2 is cyclobutyl, cyclopropyl, methylcyclopropyl or methylthiocyclopropyl, and R4 is Cl-C4alkyl that is unsubstituted or fluoro-substituted or, in the case of C2-C4alkyl, may also be substituted by methoxy or ethoxy; or wherein R4 is allyl, propargyl, phenyl, chlorophenyl, fluorophenyl, benzyl, chlorobenzyl or fluorobenzyl, while R3 is as defined above (= subgroup Ic).
Especially preferred compounds within subgroup Ic are those wherein Z0326~
R2 is cyclopropyl, and R4 is methyl, ethyl, fluoromethy1, difluoromethyl, trifluoroethyl, allyl, propargyl, phenyl or benzyl (= subgroup Icc).
Of those compounds, special mention should be made of those wherein Rl is hydrogen, Cl-C3alkyl, methoxymethyl or ethoxymethyl.
Important compounds are also those thiazolyl-S-carbonamide derivatives of formula I
wherein one of the two substituents Rl and R2 is the group -CH2-X-R4 and the other substituent is hydrogen, Cl-C4alkyl or -CH2-X-R4, X is oxygen or sulfur, R3 is as deflned above, and R4 is Cl-C4alkyl that is unsubstituted or substituted by fluorine or, in the case of C2-C4alkyl, may also be substituted by Cl-C3alkoxy; or wherein R4 is allyl, propargyl, phenyl or benzyl, the aromatic rings of the latter radicals being unsubstituted or substituted by one or two of the substituents fluorine, chlorine, methyl, ethyl, methoxy and CF3 (= subgroup ID).
Of the compounds of group ID, special mention should be made of those wherein Rl is the group -CH2-O-R4, R2 is hydrogen, Cl-C4alkyl or -CH2-O-R4, R3 is as defined above, and R4 is Cl-C4alkyl that is unsubstituted or substituted by fluorine, methoxy or by ethoxy, or wherein R4 is allyl, propargyl, pheny1, chlorophenyl, fluorophenyl, benzyl, chloro-benzyl or fluorobenzyl (subgroup IDD).
Preferred compounds of forrnula I in subgroup IDD are those wherein R4 is methyl, ethyl, fluoromethyl, difluoromethyl, trifluoroethyl, allyl, propargyl, phenyl or benzyl ~= subgroup Id).
Especially preferred compounds in the last-mentioned subgroup Id are those wherein R2 is hydrogen or Cl-C3alkyl.
Especially preferred compounds in subgroup Id are also compounds wherein Rl and R2 are each independently of the other methoxymethyl or ethoxymethyl.
- - . , ~ ,: - .
.
- 6- 203268~
Among the compounds of group ID, special mention should be made of those compounds wherein R, is hydrogen, Cl-C4alkyl or the group -CH2-O-R4, R2 is-CH2-O-R4, R3 is as defined above and R4 is cl-c4alkyl that is unsubstituted or substituted by fluorine, methoxy or by ethoxy, or wherein R4 is allyl, propargyl, phenyl, chlorophenyl, fluorophenyl, benzyl, chloro-benzyl or fluorobenzyl (= subgroup IE).
.
Preferred compounds of group IE are those wherein R4 is methyl, ethyl, fluoromethyl, difluoromethyl, trifluoroethyl, allyl, propargyl, phenyl or benzyl (= subgroup IEE).
Especially preferred compounds of group IEE are those wherein Rl is hydrogen or Cl-C3alkyl.
Furthermore, an important group of phytofungicides comprises those compounds of formula I wherein either a) R, is cH3~c2H5~n-c3H7~ isoC3H7, CH2-O-CH3, CH2-O-C2H5 or CH2-O-CHF2 or cyclopropyl, and R2 is cyclopropyl, or wherein b) Rl is CH2-O-CH3, CH2-O-C2H5, CH2-O-CHF2 or cyclopropyl, and R2 is Cl-C3alkyl, and R3 is as defined above (subgroup Alpha).
Among the compounds of the group Alpha, mention should be made of a preferred subgroup wherein Rl is cH3~c2H5~n-c3H7 or iso-C3H7, and R2 is cyclopropyl (subgroup Beta).
Furthermore, among the compounds of the group Alpha, mention should be made of afurther preferred subgroup wherein R,= CH2-O-CH3, CH2-O-C2H5 or cyclopropyl and R2= CH3, C2H5. n-C3H7, iso-C3H7 or cyclopropyl (subgroup Gamma).
Compounds of formula I are obtained by reaction of the thiazolyl-S-carboxylic acid of 203Z~8~?d formula V
, I--~ COOH (V) S
or an acid halide, an ester or an acid anhydride thereof, with an aminoacetonitri1e of formula II
CN
,.:' H2N CH R3 (II) in the presence or absence of a condensation agent or an acid acceptor, the substituents Rl, R2 and R3 bemg as defined under formula 1.
It is advantageous to use the amine component Il in slight excess with respect to component V (for example up to 2 molar equivalents).
An acid halide is to be understood as being especially a chloride, bromide or iodide, and acid esters are to be understood as being the readily reactive derivatives of Cl-C6alcohols, for example inter alia methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl and amyl esters.
The reaction of V with II is effected in the absence or preferably in the presence of a condensation agent or an acid acceptor (proton acceptor).
An acid halide of formula V can also be obtained in situ from the thiazolyl-5-carboxylic acid by reaction thereof with reactant II in the presence of a thionyl halide, for example SOCl2, and imidazole. This process variant is included in the above-mentioned process.
The temperature range for the reaction is from -20C to 150C, preferably from -5C to +80C.
The proton acceptors used may be, for example, inorganic or organic bases, for example alkali metal or aL~aline earth metal compounds, for example the hydroxides, oxides or - carbonates of lithium, sodium, potassium, magnesium, calcium, strontium and barium, or , . ' . ': . - - ~
: , - :
- 8- 203~6a~
alternatively hydrides, for example sodium hydride. Organic bases that may be mentioned are, for example, tertiary amines, such as triethylamine, triethylenediamine, pyridine and 4-dimethylaminopyridine.
Although not absolutely necessary, solvents or diluents may advantageously be used for the reaction. Examples that may be mentioned are: halogenated hydrocarbons, especially chlorinated hydrocarbons, such as tetrachloroethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichloroethylene, pentachloroethane, 1,2-dichloroethane, l,l-dichloroethane, 1,2-cis-dichloroethylene, chlorobenzene, fluorobenzene, bromobenzene, dichlorobenzene, dibromobenzene, chlorotoluene, trichlorotoluene; ethers, such as ethyl propyl ether, methyl tert.-butyl ether, n-butyl ethyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, diisopropyl ether, anisole, cyclohexyl methyl ether, diethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, thioanisole, dichlorodiethyl ether, nitrohydrocarbons, such as nitromethane, nitroethane, nitrobenzene, chloronitrobenzene, o-nitrotoluene; nitriles such as acetonitrile, butyronitrile, isobutyronitrile, benzonitrile, m-chlorobenzonitrile; aliphatic or cycloaliphatic hydrocarbons, such as heptane, hexane, octane, nonane, cymene, petroleum fractions within a boiling point range of from 70C to 190C, cyclohexane, methylcyclohexane, decalin, petroleum ether, ligroin, trimethyl-pentane, such as 2,3,3-trimethylpentane; esters, such as ethyl acetate, acetoacetic acid esters, isobutyl acetate; amides, for example formamide, methylformamide, dimethyl-forrnamide; ketones, such as acetone, methyl ethyl ketone; optionally also water.
Mixtures of said solvents and diluents also come into consideration.
The starting materials of formula II can be obtained in accordance with the Strecker synthesis by reaction of the aldehyde III with hydrocyanic acid or an alkali cyanide (for example NaCN) in the presence of ammonia or an ammonium salt:
R3 - CHO + HCN/alkali cyanide II
(III) It is advantageous to use a binary solvent system consisting of, on the one hand, an ether (diethyl ether, dioxane, THF etc.) or an aromatic hydrocarbon ~benzene, toluene, xylene) and, on the other hand, water and the operation is performed at from 0 to 100C.
203~26 The starting materials of formula V are obtained by reaction of a thioamide of formula VI
with an o~-halo-~-keto ester of formula VII to form the thiazolyl-5-carboxylic acid ester Va:
NH2 + = C R2 ~ / -HHal R~--~COOR
VI VII Va wherein R' is a Cl-C6hydrocarbon, and then, if desired, conversion into the carboxylic acid V by hydrolysis. The reaction can be carried out in a protic solvent, such as an alcohol, or in an aprotic solvent, sueh as benzene, toll~ene, cyclohexane etc.. In some cases it is advisable to add a proton acceptor, such as sodium acetate/acetic acid or a tertiary base (for example pyridine, triethylamine etc.). The reaction is initially carried out at temperatures of -60C to +40C, preferably -20C to +20C. The temperature is then increased to +30C to +140C, preferably to +50C to +110C. If, for exarnple, the operation is carried out in benzene, toluene or cyclohexane, the water that forms can be removed using a water separator.
In accordance with another process variant, the intermediate of formula V can also be obtained by first acylating the thioamide of formula VI with an acid halide of formula VIII
to form an N-acylthioamide of formula IX:
NH2 NH--C~ R2 +
RlC~ Hal-CO-R2 R1 C~
S S
VI VIII IX
The operation is advantageously carried out in an inert solvent, such as acetonitrile or tetrahydrofuran. The proton acceptor used is preferably a tertiary base, such as pyridine, 203~6~3~
triethylarnine, 4-dimethylaminopyridine etc.. The reaction should take place in a temperature range of from -40C to +80C, preferably from -20C to +20C. Compound IX is then condensed with a haloester X to form the thiazolyl-5-carboxylic acid ester Va which, if desired, is then converted into V in customary manner:
NH--C~ R2 I
Rl C~ + Hal-CH2-COOR' ~ Va IX X
For the cyclisation the N-acylthioamide IX in a protic solvent (for example a lower alcohol) or aprotic solvent is treated with an alcoholate (for example CH3-O-Na) or with NaH at temperatures of from -40C to +20C, preferably from -30C to 0C, and then the halo ester X is added at from -20C to +30C, preferably from -10C to +10C. The reaction mixture is subsequently heated for several hours at from +40 to +l 20C, preferably from +60C to +100C, in order to remove the water of reaction.
In the above-mentioned forrnulae Va to X, Rl and R2 are as defined under formula 1.
The present invention relates to the described preparation processes, including all subsidiary steps.
The present invention relates also to the novel intermediates of formula V and their esters with Cl-C6alcohols, especially those wherein Rl and R2 are as defined for subgroup Alpha.
Surprisingly, it has now been found that compounds of formula I have, for practical purposes, a very advantageous biocidal spectrum against phytopathogenic micro-organisms, especially against fungi. They have very advantageous curative, preventive and, in particular, systemic properties, and can be used for protecting numerous cultivated plants. With the compounds of formula I it is possible to inhibit or destroy the pests which occur in plants or in parts of plants (fruit, blossoms, leaves, stems, tubers, roots) in different crops of useful plants, while at the same time the parts of plants which grow later 20~68%
are also protected, for example, from attack by phytopathogenic microorganisms.
Compounds of formula I are effective, for example, against the phytopathogenic fungi belonging to the following classes: Fungi imperfecti (especially Botrytis, also Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria); Basidiomycetes (e.g.
Rhizoctonia, Hemileia, Puccinia). Furtherrnore, they are effective against the class of the Ascomycetes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula), but especially against the Oomycetes (e.g. Phytophthora, Peronospora, Bremia, Pythium, Plasmopara). The compounds of formula I can also be used as dressing agents for protecting seeds (fruit, tubers, grains) and plant cuttings against fungus infections and against phytopathogenic fungi which occur in the soil.
The invention relates also to the compositions that contain compounds of formula I as active ingredient, especially plant-protective compositions, and to their use in the agricultural sector or related fields.
The present invention relates also to the preparation of those compositions, which comprises homogeneously mixing the active ingredient with one or more of the compounds or groups of compounds described herein. The invention furthermore relates to a method of treating plants, which comprises applying thereto the novel compounds of formula I or the novel compositions.
Target crops to be protected within the scope of this invention comprise e.g. the following species of plants: cereals (wheat, barley, rye, oats, rice, maize, sorghum and related crops), beet (sugar beet and fodder beet), pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, gooseberries, raspberries and blackberries), leguminous plants (beans, lentils, peas, soybeans), oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa, groundnuts), cucumber plants (cucumber, marrows, melons), fibre plants (cotton, flax, hemp, jute), citrus fruit (oranges, lemons, grapefruit, mandarins), vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika), lauraceae (avocados, cinnamon, camphor), or plants such as tobacco, nuts, coffee, sugar cane, tea, pepper, vines, hops, aubergines, bananas and natural rubber plants, as well as ornamentals.
The compounds of formula I are normally applied in the form of compositions and can be applied to the area or plant to be treated, simultaneously or in succession, with further - 12- ~203~fi8~, compounds. These further compounds can be fertilisers, micronutrient donors or other preparations that influence plant growth. They can also be selective herbicides,insecticides, fungicides9 bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or other application-promodng adjuvants customarily employed in the art of formulation.
Suitable carriers and adjuvants can be solid or liquid and correspond to the substances expediently employed in the art of formulation, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilisers.
A preferred method of applying a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application. The number of applications and the rate of application depend on the risk of infestation by the corresponding pathogen; However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by impregnating the locus of the plant with a liquid composition or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In paddy rice crops, such granulates can be applied in metered arnounts to the flooded rice field. The compounds of formula I may, however, also be applied to seeds (coating) either by impregnating the seeds with a liquid formulation of the active ingredient or by coating them with a solid formulation. In general, any kind of propagation material of a plant may be protected by a compound of formula 1, for example the seeds.
The compounds of formula I are used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation, and are for that purpose advantageously formulated in known manner, e.g. into emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations in e.g. polymer substances. As with the nature of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. Advantageous rates of application are normally from 50 g to 5 kg of active ingredient (a.i.) per hectare, preferably from 25 g to 2 kg a.i./ha, most preferably from 30 g to 300 g a.i./ha.
The formulations, i.e. the compositions, preparations or mixtures containing the compound , ~-- 13- Z03;~68~
of formula I and, where appropriate, a solid or liquid adjuvant, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredients withextenders, e.g. solvents, solid carriers and, where appropriate, surface-active compounds (surfactants).
Suitable solvents are: aromatic hydrocarbons, preferably the fractions containing 8 to 12 carbon atoms, e.g. xylene mixtures or substituted naphthalenes, phthalates such as dibutyl phthalate or dioctyl phthalate, aliphatic hydrocarbons such as cyclohexane or paraffins, alcohols and glycols and their ethers and esters, such as ethanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones such as cyclohexanone, strongly polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, as well as vegetable oils or epoxidised vegetable oils, such as epoxidised coconut oil or soybean oil, or water.
The solid carriers used, e.g. for dusts and dispersible powders, are normally natural mineral fillers such as calcite, talcum, kaolin, montmorillonite or attapulgite.
Especially advantageous application-promoting adjuvants, which can result in a considerable reduction in the application rate, are natural (animal or vegetable) or synthetic phospholipids of the series of the cephalins and lecithins, which can be obtained, for example, from soybeans.
Depending on the nature of the compound of formula I to be formulated, suitable surface-active compounds are non-ionic, cationic and/or anionic surfactants having good emulsifying, dispersing and wetting properties. The term "surfactants" will also be understood as comprising mixtures of surfactants.
Both so-called water-soluble soaps and water-soluble synthetic surface-active compounds are suitable anionic surfactants.
Suitable soaps are the alkali metal salts, alkaline earth metal salts or unsubstituted or substituted ammonium salts of higher fatty acids (C10-C22), e.g. the sodium or potassium salts of oleic or stearic acid or of natural fatty acid mixtures which can be obtained e.g.
from coconut oil or tallow oil. Mention may also be made of fatty acid methyllaurin salts.
Suitable non-ionic surfactants are polyglycol ether derivatives of aliphatic or - ~ --2032~8 cycloaliphatic alcohols, saturated or unsaturated fatty acids and alkylphenols, said derivatives containing 3 to 30 glycol ether groups and 8 to 20 carbon atoms in the (aliphatic) hydrocarbon moiety and 6 to 18 carbon atoms in the alkyl moiety of the alkylphenols.
Representative examples of non-ionic surfactants are nonylphenol polyethoxyethanols, castor oil polyglycol ethers, polypropylene/polyethylene oxide adducts, tributylphenoxy-polyethoxyethanol, polyethylene glycol and octylphenoxypolyethoxyethanol.
Fatty acid esters of polyoxyethylene sorbitan, e.g. polyoxyethylene sorbitan trioleate, are also suitable non-ionic surfactants.
Cationic surfactants are preferably quaternary ammonium salts which contain, as N-substituent, at least one Cg-C22alkyl radical and, as further substituents, unsubstituted or halogenated lower alkyl, or benzyl or hydroxy-lower alkyl radicals.
Further surfactants customarily employed in the art of formulation are known to the person skilled in the art or can be taken from the relevant specialist literature.
The anionic, non-ionic or cationic surfactants customarily employed in the art of formu-lation are known to the person skilled in the art or can be taken from the relevant specialist literature:
"McCutcheon's Detergents & Emulsifiers Annual", Mc Publishing Corp., Glen Rock, New Jersey, 1988;
M. and J. Ash, "Encyclopedia of Surfactants", Vol. I-III, Chemical Publishing Co., New York, 1980-1981;
Dr. Helmut Stache, "Tensid-Taschenbuch", Carl Hanser Verlag, Munich/Vienna, 1981.
The agrochemical compositions usually contain 0.1 to 99 %, preferably 0.1 to 95 %, of an active ingredient of formula I, 99.9 to 1 %, preferably 99.9 to 5 %, of a solid or liquid adjuvant, and 0 to 25 %, preferably 0.1 to 25 %, of a surfactant.
Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.
.
: :
The compositions may also contain further auxiliaries such as stabilisers, antifoams, viscosity regulators, binderst tackifiers and fertilisers or other active ingredients for obtaining special effects.
The following Examples serve to illustrate the invention but do not limit the scope thereof.
reparation Example 1 a) Preparation of 2-methoxymethvl-4-methvlthiazole-5-carboxylic acid ethvl ester N ~ CH3 C113H2~ Jl--COOC2H5 20 g of methoxythioacetamide are added, with vigorous stirring, to 31.3 g of 2-chloroacetoacetic acid ethyl ester in 400 ml of benzene at room temperature and then, using a water separator, heated under reflux for 41/2 hours. After cooling to room temperature, the benzenic reaction solution is diluted with 500 ml of ethyl acetate, washed twice using 80 ml of 10 % sodium carbonate solution each time and twice using 50 ml of water each time, dried over sodium sulfate and filtered. The solvent mixture is evaporated off. The yellow oil that remains is crystallised by trituration with diisopropyl ether. The beige-coloured crystals melt at 36-37C.
b) Preparation of 2-methoxymethyl-4-methvlthiazole-5-carboxylic acid N ~CH3 CH3CH2~ S Jl_ COOH
6.7 g of 85 % potassium hydroxide in 100 ml of ethanol are added at room temperature to 22.1 g of 2-methoxymethyl-4-methylthiazole-5-carboxylic acid ethyl ester and thereaction mixture is then heated under reflux for 18 hours. After cooling, the ethanol is evaporated off and the residue is dissolved in 200 ml of water. After stirring with acdve carbon, the mixture is filtered over Hyflo and the filtrate is acidified with concentrated hydrochloric acid with vigorous stirring. The resulting yellowish crystals are filtered off, . ' - - ' .
- . .
.
, washed with water and dried~ After recrystallisation from tetrahydrofuran/petroleum ether (30-45C) (=10:1) the yellowish crystals melt at 168-169.5C.
c) Preparation of 2-(2-methoxymethyl-3-methylthiazo!yl-5-carbonylamino)-2-(3-thienyl)-acetonitrile N ~ CN
l~s~ 3 Comp. No. 68 2.38 g of thionyl chloride are added dropwise at 0C within a period of l/4 hour, with stirring, to 3.5 g of methoxymethyl-4-methylthiazole-5-carboxylic acid in 40 ml of pyri-dine. After stirring for one hour at 0C, 3.5 g of 2-(3-thienyl)-aminoacetonitrile hydrochloride are added and stirring is continued for 18 hours while passing nitrogen through the mixture. After the addition, with stirring, of 200 ml of ice-water and 100 ml of ethyl acetate, the mixture is acidified with 50 ml of concentrated hydrochloric acid; the organic phase is separated off and extraction is carried out again with 70 ml of ethyl acetate. The combined extracts are washed twice using 100 ml of lN hydrochloric acid each time and once with 100 ml of saturated sodium bicarbonate solution, dried over sodium sulfate and filtered, and the solvent is evaporated off. The yellowish oil that remains is crystallised by trituration with diisopropyl ether. The pale yellow crystals melt at 111-113C.
PreDaration Example 2 Preparation of 2-(2-methvl-4-cYclopropvlthiazolYI-5-carbonvlamino)-2-(3-thienYl)-acetonitrile N~ CN
CH3 1~ ~ C - NH- CH~3 Comp. No. 2 203268~:
8.75 g of 2-(3-thienyl)^aminoacetonitrile hydrochloride are suspended in 200 m1 of ethyl acetate and, after cooling to +5C, 12 g of triethylamine are added, with stirring, within a period of 5 minutes. With vigorous stirring, 10 g of 2-methyl-4-cyclopropylthiazole-5-carboxylic acid chloride in 100 ml of ethyl acetate are added dropwise at -5C within a period of I hour and the reaction mixture is then stirred for 2 hours at room temperature; 100 ml of water are added and the aqueous phase is separated of The ethyl acetate solution is washed twice using 50 ml of water each time, dried over sodium sulfate and filtered, and the solvent is evaporated off. The oil that remains is purified by column chromatography over silica gel (tetrahydrofuran:hexane = 1:1). After the eluant mixture has been evaporated off, the initially brown oil is crystallised by trituration with petroleum ether (50-70C) and recrystallised from hexane/-dichloromethane. The beige-coloured crystals melt at 108-110C.
The following compounds can be prepared in an analogous manner:
-~
20326~3~
Table 1: Compounds of formula Ql = 2-furan R2 Q2 = 3-furany _~ CN Q3 = 2-thienyl Rl S C--NH- CH R3 Q4 = 3-thienyl O CP.= cyclopropyl Comp Rl ~~- R2 R3 Physical F~ ~ I I I const3nt 2 -CH3 CP. Q4 m.p. 108-110C
3 -C2Hs CP. Q3 m.p. 116-117C
4 H . -CH20CH3 Q4 56 HP. CP Q4 m.p. 93-95C
7 CP . -CH2OCH3 Ql 8 -CH3 CP. Ql m.p. 67-68C
9 -CH20CH3 CP. Q4 m.p. 135-136.5C
-C2Hs -CH20CH3 Q4 .
11 CP. H Q4 12 -C ~3 CP. Q2 m.p. 91-93~C
CP. -CH3 Ql 16 CP. -CH2OCH3 Q4 18 -CH3 CP. Q3 m.p. 135-136C
''' ~ , ' ~
203268%
Com~ l~ Rl R2 R3 Physical No constant 19 -C2Hs -CH2Oc2Hs Ql cyclobutyl -CH3 Q4 22 -CH3 cyclobutyl Q4 23 -CH2OC2Hs CP. Q4 24 CP. -CH3 Q4 m.p. 132-134C
-C2Hs -CH2Oc2Hs Q4 26 CP. -CH20C~F2 Q3 27 -CH3 -CH2OCH3 Ql 29 cyclohexyl -CH3 Q4 -CH2Oc2Hs -CH2OCH3 Ql 31 CP. -CH3 Q2 32 -CH3 -CH2OCH3 Q3 m.p. 77-81C
33 CP. -CH2OC2Hs Ql 34 -C3H7-n CP. Q4 m.p. 114-115C
-CH2OCH3 ~ -CH3 Ql m.p. 80-81 C
36 -CH2Oc2Hs H Q4 39 CP. -CH3 Q3 m.p. 127-130C
41 -CH2OC2Hs -CH2OCH3 Q4 42 CP. -CH2OC2Hs Q4 43 -CH2OCHF2 . _ .. . .
' : -203~68~:
_ Comp Rl R2 R3 Physical No. constant _ 44 -C3H7-n -CH2OCH3 Q4 c~ -CH2OCH3 Q4 47 -CH2OCH2CH2OCH3 CP. Q4 48 -CH2OCH3 -CH3 Q2 m.p. 79-80C
49 -CH3 . -CH2OCH3 Q4 -CH2OCH2CH-C~2 -CH3 Q4 c~3 51 ~ -CH2OCH3 Q4 52 :-CH2OCH2CF3 H Q4 53 -CH3 -CH2Oc2Hs : Ql 54 -CH2OCH3 -CH3 ~ Q3 m.p. 96-98C
-C3H7-iso CP. Q4 m.p. 132-133C
56 ~ -CH3 Q4 57 ~3 CP. Q4 59 -CH3 -CHzOC2H5 Q4 , . :. :, . .. - ~ ., ~ . . .:
:, ~ . , , . -: : ' .:
::
.,: .: , -203~6 Comp Rl R2 R3 Physical No. constant .
61 ~CH2 ~ -CH3 Q4 63 -cH2occH3F2 CP. Q4 64 --b -CH20CH3 Q
CP ~C2Hs Ql 66 SCH3 -CH20C3H7-iso Q4 67 ~ -CH3 Ql 68 -CH20CH3 -CH3 Q4 m.p. 111-113C
69 ~U20~F -CH3 ~ ~ Q4 -CH20 H5 -CH3 Ql 71 ~ -CH20CH3 Q4 73 -CH3 -CH20CHF2 Ql 74 ~ -CH3 Q3 -C3H7-iso -CH20C2Hs Q4 . . , ~ . .
- ' . ' .
Z0~26~3 Comp. Rl R2 R3 Physical No. constant 76 _CH20CH2 ~3 -CH3 Q4 77 CP. -C2Hs Q4 m.p. 116-117.~C
78 -C2H5 CP. Q2 m.p. 84-86C
79 -CH20C2Hs -CH3 Q2 ~ -CH3 Q2 81 -c4H9-n CP. Ql 82 ~ -CH2OC2Hs Ql 1 85 I H~ l ~ I Q4 86 CP. CP. Ql m.p. 86-88C
87 ~ H3 -CH3 Q4 89 -CH2OCH2CF3 CP. Q4 90 -C2Hs CP. Q4 m.p. 81-83C
:`
. ~` .
Z03~682 Comp Rl R2 ~ R3 - Physical No. constant -- SCH3 ,.
91 ~ -CH2Oc2Hs Q4 92 -C4Hg-n CP. Q4 93 -CH2Oc2Hs -CH3 Q3 n25 1.5723 94 -C2Hs CP. Ql m.p. 73-75C
-CH2OCH3 CP. Ql m.p. 81-83C
96 -CH2OC2Hs -CH3 Q4 97 -C2Hs -CH2O
98 -CH2OCHF2 -CH3 Ql 100 ~ -C2Hs Q4 101 -CH2OCHF2 ~C2Hs Q4 io2 ~ -CH3: Q4 103 CH2OcH2cH2OcH3 -CH3 Ql 104 -CH2OCH3 -C2Hs Q4 m.p. 111-112C
106 -CH2OCH2CF3 -C2Hs Q4 107 CP. -C3H7-iso Q4 m.p. 108-111C
108 -CH2OCHF2 -C3H7-iso 109 -CH20C2Hs -C2Hs .. ' ', ~'` ,' ' ', ' .
2032G~3 Comp Rl - -~ R3 PhYsStiCnt 110 -CH20CHF2 -CH3 Q2 oil 111 -CH20C2Hs -C2Hs Q4 m.p. 126-129C
112 --b -C3H7-n Q4 113 -CH20CH3 -C3H7-iso Q 4 114 -CH20CHF2 -C3H7-iso Q4 115 cH2oCH2cH2cH3 -C2Hs Q4 116 -CH20C2Hs -C3H7-iso Q4 . , ., -;~ . . ... .
', ' 203~
Comp Rl R2 R3 Physical No. constant _ 118 -CH2Oc2Hs -C2Hs . Q3 m.p. 96-97C
119 -CH2OCH3 -C2Hs Q3 m.p. 78-83C
120 CP. -C2Hs Q3 m.p. 106-109C
121 -CH2OCH3 CP. Q3 m.p. 104-106C
122 -CH2OCH3 ~C2Hs Q2 m.p. 81-83C
123 -CH2OCH3 CP. Q2 m.p. 105-106C
124 -CH2OCH3 -C2Hs Ql m.p. 104-105C
125 -C3H7iso CP. Ql m.p. 89-92C
126 -C3H7iso . CP. Q3 m.p. 12g-131C
127 -C3H7iso CP. Q2 m.p. 109-110C
128 -c3H7n CP. Ql m.p. 86-87C
129 -c3H7n CP. Q3 m.p. 74-76C
130 -C3H7n CP. Q2 m.p. 81-83C
132 -CH2OCHF2 C2Hs Ql 133 -CH2OCHF2 C2Hs Q2 134 -CH2OCHF2 C2Hs Q3 135 -CH2OCHF2 CP. Ql 136 -CH2OCHF2 CP. Q2 137 -CH2OCHF2 CP. __ 203~G~
_ . . __ Comp Rl R2 R3 Physical No. constant _ _ ._ ..
138 CP~ CP. . Q2 m.p. 103-105C
13g CP. CP. Q3 m.p. 123-126C
140 CP. -C3H7-n Ql m.p. 106-108C
141 CP. -C3H7iso Q2 m.p. 108-110C
142 CP. -C3H7iso Ql m.p. 97-100C
143 -CH2OCH3 -C3H7iso Q3 m.p. 89-91C
144 CP. -C3H7-n Q2 m.p. 111-114C
145 CP. . -C3H7iso Q3 m.p. 101-103C
146 -CH2Oc2Hs ~ CP. Ql m.p. 116-118C
147 -CH2OCH3 -C3H7-n Q3 m.p. 98-101C
148 -cH2oc2Hs CP. Q3 m.p. 123-125C
149 -CH2OCH3 -C3H7iso Ql m.p. 87-90C
150 -CH2OCH3 -C3H7-n Ql m.p. 91-94C
151 CP. -C3H7-n Q3 m.p. 103-106C
152 -CH2OCH3 -C3H7-n Q2 m.p. 85-87C
153 -CH2OCH3 -C3H7iso Q2 m.p. 93-95C
154 CP. -C3H7-n Q4 m.p. 114-120C
155 -CH2OCH3 -C3H7-rl Q4 m.p. 124-126C
156 -CH2OC2Hs CP. Q2 m.p. 109-111C
203;~
Table 2: Intermediates of fo~nula V
_ ~ CP.= cyclopropyl R~ S COOH
Comp Rl R2 ~---~ Physical No. constant 2.1 CP. CH3 m.p. 198-200C
2~2 CP. C2Hs m.p. 96-97C
2.3 CP. C3H7-n m.p. 104-106C
2.4 CP. . C3H7-iso m.p. 84-87C
2.5 CH3 CP. m.p. 190-191C
2.6 C2Hs CP. m.p. 158-159C
2.7 C3H7-iso CP. m.p. 122-123C
2.8 C3H7-n CP. m.p. 161-162C
2.9 -CH2OCH3 CH3 m.p. 168-169.5C
2.10 -CH2OCH3 C2Hs m.p. 146-147C
2.11 -CH2OCH3 CP. m.p. 159-161C
2.12 -CH2OC2Hs CH3 m.p. 185-186C
2.13 -CH2OC2Hs C2Hs m.p. 114-115C
2.14 -CH2OC2Hs CP. m.p. 132-134C
2.15 CP. CP. m.p. 102-104C
2.16 -CH2OCHF2 CH3 2.17 -CH2OCHF2 C2Hs 2.18 -CH2OCHF2 CP.
2.19 -CH2OCH3 C3H7-n m.p. 137-139C
2.20 -CH2OCH3 C3H7-iso m.p. 148 151C
20326?~3~
In the presence of an acid catalyst, such as HCl, it is readily possible to obtain the corresponding carboxylic acid Cl-C6alkyl esters from the acids of Table 2 by esterification with methanol, ethanol or one of the isomeric alcohols propanol, pentanol and hexanol.
2.Formulation Examples for active ingredients of formula I (throu~ehout percenta~es are bv wei~ht) 2.1. Wettable powder a) b) c) acompoundofTable 1 25 % 50% 75 %
sodium lignosulfonate 5 % 5 %
sodiumlaurylsulfate 3 % - 5 %
sodium diisobutylnaphthalenesulfonate - 6 % 10 %
octylphenol polyethylene glycol ether - 2 %
(7-8 moles of ethylene oxide) highly dispersed silicic acid 5 % 10 % 10 %
kaolin 62 % 27 %
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspensions of the desired concentration.
2.2. Emulsifiable concentrate a compound of Table 1 10 %
octylphenol polyethylene glycol ether 3 %
(4-5 moles of ethylene oxide) calcium dodecylbenzenesulfonate 3 %
cyclohexanone 34 %
xylene mixture 50 %
Emulsions of any required concentration can be produced from this concentrate bydilution with water.
2.3. Dusts a) b) a compound of Table 1 5 % 8 %
talcum 95 %
kaolin - 92 %
.
, . , , , ,,: -~ . .
': , ' . ': ! ~ ~
` ~ .
- 29 - Z03Z68~:
Ready-for-use dusts are obtained by mixing the active ingredient with the carrier, and grinding the mixture in a suitable mill.
2.4. Extruder granulate a compound of Table 1 10 %
sodium lignosulfonate 2 %
carboxymethylcellulose 1 %
kaolin 87 %
The active ingredient is mixed and ground with the adjuvants, and the mixture ismoistened with water. The mixture is extruded and subsequently dried in a stream of air.
2.5 Coa~ranu!ate a compound of Table 1 3 %
polyethylene glycol (mol. wt. 200) 3 %
kaolin 94 %
The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granulates are obtained in this manner.
2.6. Suspension concentrate a compound of Table 1 40 %
ethylene glycol 10 %
nonylphenol polyethylene glycol ether 6 %
(15 moles of ethylene oxide) sodium lignosulfonate 10 %
carboxymethylcellulose 1 %
37% aqueous formaldehyde solution 0.2 %
silicone oil in the form of a 75%
aqueous emulsion 0.8 %
water 32 %
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired concentration can be .
203~6?3~:
obtained by dilution with water.
3~ Biolo~ical Examples I. Action against Phvtophthora infestans on tomato plants a) Curative action After a cultivation period of 3 weeks, tomato plants of the "Roter Gnom" varietyare sprayed with a zoospore suspension of the fungus and incubated in a cabinet at 18 to 20 and saturated humidity. The humidification is discontinued after 24 hours. When the plants have dried, they are sprayed with a mixture containing a wettable powder formulation of the test compound in a concentration of 600, 200 or 60 ppm. When the spray-coating has dried, the plants are returned to the humidity cabinet for four days. The effectiveness of the test compounds is evaluated on the basis of the number and size of the typical leaf specks occurring after that time.
b) Preventive svstemic action A wettable powder forrnulation of the test compound is applied in a concentration of 60 ppm (based on the volume of the soil) to the surface of the soil of three-week-old tomato plants of the "Roter Gnom" variety in pots. After three days theunderside of the leaves of the plants are sprayed with a zoospore suspension of Phytophthora infestans. The plants are then kept in a spraying cabinet at 18 to 20C and saturated humidity for 5 days. The effectiveness of the test compounds is evaluated on the basis of the number and size of the typical leaf specks that form after that tirne.
.
The following compounds of Table 1 inhibit disease attack to less than 10 %: Nos. 2,3,5, 8,9,12,18,24,32,34,35,39,48,54,55,63,68,77,78,90,93,95,98,104,107,110, 111, 113, 116, 118 to 130 and 138 to 156.
II. Action a~ainst Plasmopara viticola (Bert.et Curt.) (Berl. et DeToni) on vines a) Residual preventive action Vine cuttings of the "Chasselas" variety are raised in a greenhouse. In the 10-leaf stage, 3 plants are sprayed with a mixture prepared from a wettable powder ,. - :; ,:
'~ ' ' ' , 203Z6?3~, formulation of the test compound (200 ppm of active ingredient). After the spMy-coating has dried, the undersides of the leaves of the plants are uniforrnly infected with a spore suspension of the fungus. The plants are then kept in a humidity chamber for 8 days. After this time the control plants exhibit clear symptoms of disease. The effectiveness of the test compounds is evaluated on thebasis of the number and size of the infection sites on the treated plants.
b) Curative action Vine cuttings of the "Chasselas" variety are raised in a greenhouse and in the 10-leaf stage the undersides of the leaves are infected with a spore suspension of Plasmopara viticola. After 24 hours in a humidity chamber the plants are sprayedwith an active ingredient mixture prepared from a wettable powder formulation ofthe test compound (500 ppm of active ingredient). The plants are then kept in the humidity cabinet for a further 7 days. After this time the control plants exhibit clear symptoms of disease. The effectiveness of the test compounds is evaluated on the basis of the number and size of the infection sites on the treated plants.
In this test too, all the compounds mentioned in Example 1 inhibit disease attack to less than 10 %.
m. Action against Pvthium debaryanum on su~ar beet (Beta vul~aris) a) Action after soil apRlication The fungus is cultured on sterile oat grains and added to a soiVsand mixture. The infected soil is introduced into pots and sown with sugar beet seeds. Immediately after sowing, wettable powder formulations of the test compounds in the form of aqueous suspensions are poured onto the soil (20 ppm of active ingredient, basedon the volume of the soil). The pots are then placed in a greenhouse at 20-24C for 2-3 weeks. The soil is kept constantly uniformly wet by lightly spraying with water. The test is evaluated by determining the emergence rate of the sugar beetplants and the proportion of healthy and diseased plants.
b) Action after dressin~
The fungus is cultured on sterile oat grains and added to a soiVsand mixture. The infected soil is introduced into pots and sown with sugar beet seeds that have been dressed with a dressing powder formulation of the test compounds (1000 ppm of Z03~fi?3~
active ingredient, based on the weight of the seeds). The pots are placed in a greenhouse at 20-24C for 2-3 weeks. The soil is kept uniformly wet by lightly spraying with water. The test is evaluated by determining the emergence rate of the sugar béet plants and the proportion of healthy and diseased plants.
An emergence rate of more than 80 % is obtained with compounds of Table 1. The corresponding control plants exhibit an emergence rate of less than 30 % and have an unhealthy appearance.
Haloalkyl indicates mono- to per-halogenated radicals, for example CHCl2, CH2F, CCI3, CH2CI, CHF2, CF3, CH2C~2Br, C2CI5, C~12Br, CHBrCI etc.. Depending upon the number of carbon atoms indicated, cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
The compounds of formula I are oils or solids that are stable at room temperature and are distinguished by valuable microbicidal properlies. They can be used preventively and curatively in the agricultural sector or related fields for controlling plant-destructive microorganisms. The compounds of formula I according to the invention are, when used in low concentrations, distinguished not only by excellent microbicidal, especially fungi-cidal, activity but also by especially good plant tolerability.
The compounds of formula 1 have an asymmetric carbon atom adjacent to the nitrile group. They can therefore be cleaved into optical antipodes in customary manner. These antipodes have different microbicidal actions.
The invention relates both to the free compounds of formula I and to the addition salts thereof with inorganic and organic acids and the complexes thereof with metal salts.
Salts according to the invention are especially addition salts with acceptable inorganic or organic acids, for example hydrohalic acids, for example hydrochloric, hydrobromic or hydriodic acid, sulfuric acid, phosphoric acid, phosphorous acid, nitric acid, or organic acids such as acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, glycolic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid, oxalic acid, formic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, salicylic acid, p-aminosalicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid or 1,2-naphthalenedisulfonic acid.
Metal salt complexes of forrnula I consist of the underlying organic molecule and an inorganic or organic metal salt, for example the halides, nitrates, sulfates, phosphates, acetates, trifluoroacetates, trichloroacetates, propionates, tartrates, sulfonates, salicylates, benzoates etc. of the elements of main group II, such as calcium and magnesium, and main groups III and IV, such as aluminium, tin or lead, and of subgroups I to Vlll, such as chromium, manganese, iron, cobalt, nickel, copper, zinc, etc.. Subgroup elements of the 4th period are preferred. The metals can be present in any of the various valencies 3 203268~
attributed to them. The metal complexes may be mono- or poly-nuclear, that is to say they may contain one or more organic molecule components as ligands.
An important group of phytofungicides and insecticides comprises those of formula I
wherein one of the two subsdtuents Rl and R2 is C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio, and the other substituent is d) cyclobutyl, cyclopropyl, methylcyclopropyl or methylthiocyclopropyl, e) the group -CH2-X-R4 or f) hydrogen or Cl-C4alkyl, while R3, X and R4 are as defined above.
Here and hereinbelow this group is referred to as compound group IA.
Among the compounds of group IA, special mention should be made of those wherein one of the two substituents Rl and R2 is C3-C6cycloalkyl and the other is cyclobutyl or cyclo-propyl, while R3 is as defined above (group IAA), and of those, in turn, those compounds wherein Rl and R2 are cyclopropyl.
Important compounds are also those of group IA wherein Rl is C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio, R2 is hydrogen, Cl-C4alkyl or the group -CH2-X-R4, X is oxygen or sulfur, and R4 is Cl-C4alkyl that is unsubstituted or substituted by fluorine or, in the case of C2-C4alkyl, may also be substituted by Cl-C3alkoxy; or wherein R4 is allyl, propargyl, phenyl or benzyl, the aromatic rings of the latter radicals being unsubstituted or substituted by one or two of the substituents fluorine, chlorine, methyl, ethyl, methoxy and CF3, while R3 is as defined above (group IB).
Those compounds of group IB wherein X is oxygen are preferred (group IBB).
Important compounds within group IBB are those wherein Rl is cyclobutyl, cyclopropyl, methylcyclopropyl or methylthiocyclopropyl, R2 is hydrogen, Cl-C4alkyl or -CH2-O-R4, wherein R4 is C1-C4alkyl that is unsubstituted or substituted by fluorine, methoxy or by ethoxy, or - : ~ . ..
:: .
.. . - ~.
:
Z0326?3 wherein R4 is allyl, propargyl, phenyl, chlorophenyl, fluorophenyl, benzyl, chloro-benzyl or fluorobenzyl (= subgroup Ib).
Preferred compounds within group Ib are those wherein Rl is cyclopropyl, R2 is hydrogen, Cl-C4alkyl or -CH2-O-R4, wherein R4 is methyl, ethyl, fluoromethyl, difluoromethyl, trifluoroethyl, allyl, propargyl, phenyl or benzyl, while R3 is as defined above (= subgroup Ibb).
Especially preferred compounds within group Ibb are those wherein R2 is hydrogen, C~-C3alkyl, methoxymethyl or ethoxymethyl.
Important compounds are also those of group la wherein Rl is hydrogen, Cl-C4alkyl or the group -CH2-X-R4, X is oxygen or sulfur, and R4 is Cl-C4alkyl that is unsubstituted or substituted by fluorine or, in the case of C2-C4alkyl, may also be substituted by Cl-C3alkoxy; or wherein R4 is a!lyl, propargyl, phenyl or benzyl, the aromatic rings of the latter radicals being unsubstituted or substituted by one or two of the substituents fluorine, chlorine, methyl, ethyl, methoxy and CF3, while R2 is C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio, while R3 is as defined above (= group IC), especially those wherein X is oxygen (= group ICC).
Within that group ICC, preferred compounds are those wherein Rl is hydrogen, Cl-C4alkyl r-CH2-O-R4-R2 is cyclobutyl, cyclopropyl, methylcyclopropyl or methylthiocyclopropyl, and R4 is Cl-C4alkyl that is unsubstituted or fluoro-substituted or, in the case of C2-C4alkyl, may also be substituted by methoxy or ethoxy; or wherein R4 is allyl, propargyl, phenyl, chlorophenyl, fluorophenyl, benzyl, chlorobenzyl or fluorobenzyl, while R3 is as defined above (= subgroup Ic).
Especially preferred compounds within subgroup Ic are those wherein Z0326~
R2 is cyclopropyl, and R4 is methyl, ethyl, fluoromethy1, difluoromethyl, trifluoroethyl, allyl, propargyl, phenyl or benzyl (= subgroup Icc).
Of those compounds, special mention should be made of those wherein Rl is hydrogen, Cl-C3alkyl, methoxymethyl or ethoxymethyl.
Important compounds are also those thiazolyl-S-carbonamide derivatives of formula I
wherein one of the two substituents Rl and R2 is the group -CH2-X-R4 and the other substituent is hydrogen, Cl-C4alkyl or -CH2-X-R4, X is oxygen or sulfur, R3 is as deflned above, and R4 is Cl-C4alkyl that is unsubstituted or substituted by fluorine or, in the case of C2-C4alkyl, may also be substituted by Cl-C3alkoxy; or wherein R4 is allyl, propargyl, phenyl or benzyl, the aromatic rings of the latter radicals being unsubstituted or substituted by one or two of the substituents fluorine, chlorine, methyl, ethyl, methoxy and CF3 (= subgroup ID).
Of the compounds of group ID, special mention should be made of those wherein Rl is the group -CH2-O-R4, R2 is hydrogen, Cl-C4alkyl or -CH2-O-R4, R3 is as defined above, and R4 is Cl-C4alkyl that is unsubstituted or substituted by fluorine, methoxy or by ethoxy, or wherein R4 is allyl, propargyl, pheny1, chlorophenyl, fluorophenyl, benzyl, chloro-benzyl or fluorobenzyl (subgroup IDD).
Preferred compounds of forrnula I in subgroup IDD are those wherein R4 is methyl, ethyl, fluoromethyl, difluoromethyl, trifluoroethyl, allyl, propargyl, phenyl or benzyl ~= subgroup Id).
Especially preferred compounds in the last-mentioned subgroup Id are those wherein R2 is hydrogen or Cl-C3alkyl.
Especially preferred compounds in subgroup Id are also compounds wherein Rl and R2 are each independently of the other methoxymethyl or ethoxymethyl.
- - . , ~ ,: - .
.
- 6- 203268~
Among the compounds of group ID, special mention should be made of those compounds wherein R, is hydrogen, Cl-C4alkyl or the group -CH2-O-R4, R2 is-CH2-O-R4, R3 is as defined above and R4 is cl-c4alkyl that is unsubstituted or substituted by fluorine, methoxy or by ethoxy, or wherein R4 is allyl, propargyl, phenyl, chlorophenyl, fluorophenyl, benzyl, chloro-benzyl or fluorobenzyl (= subgroup IE).
.
Preferred compounds of group IE are those wherein R4 is methyl, ethyl, fluoromethyl, difluoromethyl, trifluoroethyl, allyl, propargyl, phenyl or benzyl (= subgroup IEE).
Especially preferred compounds of group IEE are those wherein Rl is hydrogen or Cl-C3alkyl.
Furthermore, an important group of phytofungicides comprises those compounds of formula I wherein either a) R, is cH3~c2H5~n-c3H7~ isoC3H7, CH2-O-CH3, CH2-O-C2H5 or CH2-O-CHF2 or cyclopropyl, and R2 is cyclopropyl, or wherein b) Rl is CH2-O-CH3, CH2-O-C2H5, CH2-O-CHF2 or cyclopropyl, and R2 is Cl-C3alkyl, and R3 is as defined above (subgroup Alpha).
Among the compounds of the group Alpha, mention should be made of a preferred subgroup wherein Rl is cH3~c2H5~n-c3H7 or iso-C3H7, and R2 is cyclopropyl (subgroup Beta).
Furthermore, among the compounds of the group Alpha, mention should be made of afurther preferred subgroup wherein R,= CH2-O-CH3, CH2-O-C2H5 or cyclopropyl and R2= CH3, C2H5. n-C3H7, iso-C3H7 or cyclopropyl (subgroup Gamma).
Compounds of formula I are obtained by reaction of the thiazolyl-S-carboxylic acid of 203Z~8~?d formula V
, I--~ COOH (V) S
or an acid halide, an ester or an acid anhydride thereof, with an aminoacetonitri1e of formula II
CN
,.:' H2N CH R3 (II) in the presence or absence of a condensation agent or an acid acceptor, the substituents Rl, R2 and R3 bemg as defined under formula 1.
It is advantageous to use the amine component Il in slight excess with respect to component V (for example up to 2 molar equivalents).
An acid halide is to be understood as being especially a chloride, bromide or iodide, and acid esters are to be understood as being the readily reactive derivatives of Cl-C6alcohols, for example inter alia methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl and amyl esters.
The reaction of V with II is effected in the absence or preferably in the presence of a condensation agent or an acid acceptor (proton acceptor).
An acid halide of formula V can also be obtained in situ from the thiazolyl-5-carboxylic acid by reaction thereof with reactant II in the presence of a thionyl halide, for example SOCl2, and imidazole. This process variant is included in the above-mentioned process.
The temperature range for the reaction is from -20C to 150C, preferably from -5C to +80C.
The proton acceptors used may be, for example, inorganic or organic bases, for example alkali metal or aL~aline earth metal compounds, for example the hydroxides, oxides or - carbonates of lithium, sodium, potassium, magnesium, calcium, strontium and barium, or , . ' . ': . - - ~
: , - :
- 8- 203~6a~
alternatively hydrides, for example sodium hydride. Organic bases that may be mentioned are, for example, tertiary amines, such as triethylamine, triethylenediamine, pyridine and 4-dimethylaminopyridine.
Although not absolutely necessary, solvents or diluents may advantageously be used for the reaction. Examples that may be mentioned are: halogenated hydrocarbons, especially chlorinated hydrocarbons, such as tetrachloroethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichloroethylene, pentachloroethane, 1,2-dichloroethane, l,l-dichloroethane, 1,2-cis-dichloroethylene, chlorobenzene, fluorobenzene, bromobenzene, dichlorobenzene, dibromobenzene, chlorotoluene, trichlorotoluene; ethers, such as ethyl propyl ether, methyl tert.-butyl ether, n-butyl ethyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, diisopropyl ether, anisole, cyclohexyl methyl ether, diethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, thioanisole, dichlorodiethyl ether, nitrohydrocarbons, such as nitromethane, nitroethane, nitrobenzene, chloronitrobenzene, o-nitrotoluene; nitriles such as acetonitrile, butyronitrile, isobutyronitrile, benzonitrile, m-chlorobenzonitrile; aliphatic or cycloaliphatic hydrocarbons, such as heptane, hexane, octane, nonane, cymene, petroleum fractions within a boiling point range of from 70C to 190C, cyclohexane, methylcyclohexane, decalin, petroleum ether, ligroin, trimethyl-pentane, such as 2,3,3-trimethylpentane; esters, such as ethyl acetate, acetoacetic acid esters, isobutyl acetate; amides, for example formamide, methylformamide, dimethyl-forrnamide; ketones, such as acetone, methyl ethyl ketone; optionally also water.
Mixtures of said solvents and diluents also come into consideration.
The starting materials of formula II can be obtained in accordance with the Strecker synthesis by reaction of the aldehyde III with hydrocyanic acid or an alkali cyanide (for example NaCN) in the presence of ammonia or an ammonium salt:
R3 - CHO + HCN/alkali cyanide II
(III) It is advantageous to use a binary solvent system consisting of, on the one hand, an ether (diethyl ether, dioxane, THF etc.) or an aromatic hydrocarbon ~benzene, toluene, xylene) and, on the other hand, water and the operation is performed at from 0 to 100C.
203~26 The starting materials of formula V are obtained by reaction of a thioamide of formula VI
with an o~-halo-~-keto ester of formula VII to form the thiazolyl-5-carboxylic acid ester Va:
NH2 + = C R2 ~ / -HHal R~--~COOR
VI VII Va wherein R' is a Cl-C6hydrocarbon, and then, if desired, conversion into the carboxylic acid V by hydrolysis. The reaction can be carried out in a protic solvent, such as an alcohol, or in an aprotic solvent, sueh as benzene, toll~ene, cyclohexane etc.. In some cases it is advisable to add a proton acceptor, such as sodium acetate/acetic acid or a tertiary base (for example pyridine, triethylamine etc.). The reaction is initially carried out at temperatures of -60C to +40C, preferably -20C to +20C. The temperature is then increased to +30C to +140C, preferably to +50C to +110C. If, for exarnple, the operation is carried out in benzene, toluene or cyclohexane, the water that forms can be removed using a water separator.
In accordance with another process variant, the intermediate of formula V can also be obtained by first acylating the thioamide of formula VI with an acid halide of formula VIII
to form an N-acylthioamide of formula IX:
NH2 NH--C~ R2 +
RlC~ Hal-CO-R2 R1 C~
S S
VI VIII IX
The operation is advantageously carried out in an inert solvent, such as acetonitrile or tetrahydrofuran. The proton acceptor used is preferably a tertiary base, such as pyridine, 203~6~3~
triethylarnine, 4-dimethylaminopyridine etc.. The reaction should take place in a temperature range of from -40C to +80C, preferably from -20C to +20C. Compound IX is then condensed with a haloester X to form the thiazolyl-5-carboxylic acid ester Va which, if desired, is then converted into V in customary manner:
NH--C~ R2 I
Rl C~ + Hal-CH2-COOR' ~ Va IX X
For the cyclisation the N-acylthioamide IX in a protic solvent (for example a lower alcohol) or aprotic solvent is treated with an alcoholate (for example CH3-O-Na) or with NaH at temperatures of from -40C to +20C, preferably from -30C to 0C, and then the halo ester X is added at from -20C to +30C, preferably from -10C to +10C. The reaction mixture is subsequently heated for several hours at from +40 to +l 20C, preferably from +60C to +100C, in order to remove the water of reaction.
In the above-mentioned forrnulae Va to X, Rl and R2 are as defined under formula 1.
The present invention relates to the described preparation processes, including all subsidiary steps.
The present invention relates also to the novel intermediates of formula V and their esters with Cl-C6alcohols, especially those wherein Rl and R2 are as defined for subgroup Alpha.
Surprisingly, it has now been found that compounds of formula I have, for practical purposes, a very advantageous biocidal spectrum against phytopathogenic micro-organisms, especially against fungi. They have very advantageous curative, preventive and, in particular, systemic properties, and can be used for protecting numerous cultivated plants. With the compounds of formula I it is possible to inhibit or destroy the pests which occur in plants or in parts of plants (fruit, blossoms, leaves, stems, tubers, roots) in different crops of useful plants, while at the same time the parts of plants which grow later 20~68%
are also protected, for example, from attack by phytopathogenic microorganisms.
Compounds of formula I are effective, for example, against the phytopathogenic fungi belonging to the following classes: Fungi imperfecti (especially Botrytis, also Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria); Basidiomycetes (e.g.
Rhizoctonia, Hemileia, Puccinia). Furtherrnore, they are effective against the class of the Ascomycetes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula), but especially against the Oomycetes (e.g. Phytophthora, Peronospora, Bremia, Pythium, Plasmopara). The compounds of formula I can also be used as dressing agents for protecting seeds (fruit, tubers, grains) and plant cuttings against fungus infections and against phytopathogenic fungi which occur in the soil.
The invention relates also to the compositions that contain compounds of formula I as active ingredient, especially plant-protective compositions, and to their use in the agricultural sector or related fields.
The present invention relates also to the preparation of those compositions, which comprises homogeneously mixing the active ingredient with one or more of the compounds or groups of compounds described herein. The invention furthermore relates to a method of treating plants, which comprises applying thereto the novel compounds of formula I or the novel compositions.
Target crops to be protected within the scope of this invention comprise e.g. the following species of plants: cereals (wheat, barley, rye, oats, rice, maize, sorghum and related crops), beet (sugar beet and fodder beet), pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, gooseberries, raspberries and blackberries), leguminous plants (beans, lentils, peas, soybeans), oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa, groundnuts), cucumber plants (cucumber, marrows, melons), fibre plants (cotton, flax, hemp, jute), citrus fruit (oranges, lemons, grapefruit, mandarins), vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika), lauraceae (avocados, cinnamon, camphor), or plants such as tobacco, nuts, coffee, sugar cane, tea, pepper, vines, hops, aubergines, bananas and natural rubber plants, as well as ornamentals.
The compounds of formula I are normally applied in the form of compositions and can be applied to the area or plant to be treated, simultaneously or in succession, with further - 12- ~203~fi8~, compounds. These further compounds can be fertilisers, micronutrient donors or other preparations that influence plant growth. They can also be selective herbicides,insecticides, fungicides9 bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or other application-promodng adjuvants customarily employed in the art of formulation.
Suitable carriers and adjuvants can be solid or liquid and correspond to the substances expediently employed in the art of formulation, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilisers.
A preferred method of applying a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application. The number of applications and the rate of application depend on the risk of infestation by the corresponding pathogen; However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by impregnating the locus of the plant with a liquid composition or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In paddy rice crops, such granulates can be applied in metered arnounts to the flooded rice field. The compounds of formula I may, however, also be applied to seeds (coating) either by impregnating the seeds with a liquid formulation of the active ingredient or by coating them with a solid formulation. In general, any kind of propagation material of a plant may be protected by a compound of formula 1, for example the seeds.
The compounds of formula I are used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation, and are for that purpose advantageously formulated in known manner, e.g. into emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations in e.g. polymer substances. As with the nature of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. Advantageous rates of application are normally from 50 g to 5 kg of active ingredient (a.i.) per hectare, preferably from 25 g to 2 kg a.i./ha, most preferably from 30 g to 300 g a.i./ha.
The formulations, i.e. the compositions, preparations or mixtures containing the compound , ~-- 13- Z03;~68~
of formula I and, where appropriate, a solid or liquid adjuvant, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredients withextenders, e.g. solvents, solid carriers and, where appropriate, surface-active compounds (surfactants).
Suitable solvents are: aromatic hydrocarbons, preferably the fractions containing 8 to 12 carbon atoms, e.g. xylene mixtures or substituted naphthalenes, phthalates such as dibutyl phthalate or dioctyl phthalate, aliphatic hydrocarbons such as cyclohexane or paraffins, alcohols and glycols and their ethers and esters, such as ethanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones such as cyclohexanone, strongly polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, as well as vegetable oils or epoxidised vegetable oils, such as epoxidised coconut oil or soybean oil, or water.
The solid carriers used, e.g. for dusts and dispersible powders, are normally natural mineral fillers such as calcite, talcum, kaolin, montmorillonite or attapulgite.
Especially advantageous application-promoting adjuvants, which can result in a considerable reduction in the application rate, are natural (animal or vegetable) or synthetic phospholipids of the series of the cephalins and lecithins, which can be obtained, for example, from soybeans.
Depending on the nature of the compound of formula I to be formulated, suitable surface-active compounds are non-ionic, cationic and/or anionic surfactants having good emulsifying, dispersing and wetting properties. The term "surfactants" will also be understood as comprising mixtures of surfactants.
Both so-called water-soluble soaps and water-soluble synthetic surface-active compounds are suitable anionic surfactants.
Suitable soaps are the alkali metal salts, alkaline earth metal salts or unsubstituted or substituted ammonium salts of higher fatty acids (C10-C22), e.g. the sodium or potassium salts of oleic or stearic acid or of natural fatty acid mixtures which can be obtained e.g.
from coconut oil or tallow oil. Mention may also be made of fatty acid methyllaurin salts.
Suitable non-ionic surfactants are polyglycol ether derivatives of aliphatic or - ~ --2032~8 cycloaliphatic alcohols, saturated or unsaturated fatty acids and alkylphenols, said derivatives containing 3 to 30 glycol ether groups and 8 to 20 carbon atoms in the (aliphatic) hydrocarbon moiety and 6 to 18 carbon atoms in the alkyl moiety of the alkylphenols.
Representative examples of non-ionic surfactants are nonylphenol polyethoxyethanols, castor oil polyglycol ethers, polypropylene/polyethylene oxide adducts, tributylphenoxy-polyethoxyethanol, polyethylene glycol and octylphenoxypolyethoxyethanol.
Fatty acid esters of polyoxyethylene sorbitan, e.g. polyoxyethylene sorbitan trioleate, are also suitable non-ionic surfactants.
Cationic surfactants are preferably quaternary ammonium salts which contain, as N-substituent, at least one Cg-C22alkyl radical and, as further substituents, unsubstituted or halogenated lower alkyl, or benzyl or hydroxy-lower alkyl radicals.
Further surfactants customarily employed in the art of formulation are known to the person skilled in the art or can be taken from the relevant specialist literature.
The anionic, non-ionic or cationic surfactants customarily employed in the art of formu-lation are known to the person skilled in the art or can be taken from the relevant specialist literature:
"McCutcheon's Detergents & Emulsifiers Annual", Mc Publishing Corp., Glen Rock, New Jersey, 1988;
M. and J. Ash, "Encyclopedia of Surfactants", Vol. I-III, Chemical Publishing Co., New York, 1980-1981;
Dr. Helmut Stache, "Tensid-Taschenbuch", Carl Hanser Verlag, Munich/Vienna, 1981.
The agrochemical compositions usually contain 0.1 to 99 %, preferably 0.1 to 95 %, of an active ingredient of formula I, 99.9 to 1 %, preferably 99.9 to 5 %, of a solid or liquid adjuvant, and 0 to 25 %, preferably 0.1 to 25 %, of a surfactant.
Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.
.
: :
The compositions may also contain further auxiliaries such as stabilisers, antifoams, viscosity regulators, binderst tackifiers and fertilisers or other active ingredients for obtaining special effects.
The following Examples serve to illustrate the invention but do not limit the scope thereof.
reparation Example 1 a) Preparation of 2-methoxymethvl-4-methvlthiazole-5-carboxylic acid ethvl ester N ~ CH3 C113H2~ Jl--COOC2H5 20 g of methoxythioacetamide are added, with vigorous stirring, to 31.3 g of 2-chloroacetoacetic acid ethyl ester in 400 ml of benzene at room temperature and then, using a water separator, heated under reflux for 41/2 hours. After cooling to room temperature, the benzenic reaction solution is diluted with 500 ml of ethyl acetate, washed twice using 80 ml of 10 % sodium carbonate solution each time and twice using 50 ml of water each time, dried over sodium sulfate and filtered. The solvent mixture is evaporated off. The yellow oil that remains is crystallised by trituration with diisopropyl ether. The beige-coloured crystals melt at 36-37C.
b) Preparation of 2-methoxymethyl-4-methvlthiazole-5-carboxylic acid N ~CH3 CH3CH2~ S Jl_ COOH
6.7 g of 85 % potassium hydroxide in 100 ml of ethanol are added at room temperature to 22.1 g of 2-methoxymethyl-4-methylthiazole-5-carboxylic acid ethyl ester and thereaction mixture is then heated under reflux for 18 hours. After cooling, the ethanol is evaporated off and the residue is dissolved in 200 ml of water. After stirring with acdve carbon, the mixture is filtered over Hyflo and the filtrate is acidified with concentrated hydrochloric acid with vigorous stirring. The resulting yellowish crystals are filtered off, . ' - - ' .
- . .
.
, washed with water and dried~ After recrystallisation from tetrahydrofuran/petroleum ether (30-45C) (=10:1) the yellowish crystals melt at 168-169.5C.
c) Preparation of 2-(2-methoxymethyl-3-methylthiazo!yl-5-carbonylamino)-2-(3-thienyl)-acetonitrile N ~ CN
l~s~ 3 Comp. No. 68 2.38 g of thionyl chloride are added dropwise at 0C within a period of l/4 hour, with stirring, to 3.5 g of methoxymethyl-4-methylthiazole-5-carboxylic acid in 40 ml of pyri-dine. After stirring for one hour at 0C, 3.5 g of 2-(3-thienyl)-aminoacetonitrile hydrochloride are added and stirring is continued for 18 hours while passing nitrogen through the mixture. After the addition, with stirring, of 200 ml of ice-water and 100 ml of ethyl acetate, the mixture is acidified with 50 ml of concentrated hydrochloric acid; the organic phase is separated off and extraction is carried out again with 70 ml of ethyl acetate. The combined extracts are washed twice using 100 ml of lN hydrochloric acid each time and once with 100 ml of saturated sodium bicarbonate solution, dried over sodium sulfate and filtered, and the solvent is evaporated off. The yellowish oil that remains is crystallised by trituration with diisopropyl ether. The pale yellow crystals melt at 111-113C.
PreDaration Example 2 Preparation of 2-(2-methvl-4-cYclopropvlthiazolYI-5-carbonvlamino)-2-(3-thienYl)-acetonitrile N~ CN
CH3 1~ ~ C - NH- CH~3 Comp. No. 2 203268~:
8.75 g of 2-(3-thienyl)^aminoacetonitrile hydrochloride are suspended in 200 m1 of ethyl acetate and, after cooling to +5C, 12 g of triethylamine are added, with stirring, within a period of 5 minutes. With vigorous stirring, 10 g of 2-methyl-4-cyclopropylthiazole-5-carboxylic acid chloride in 100 ml of ethyl acetate are added dropwise at -5C within a period of I hour and the reaction mixture is then stirred for 2 hours at room temperature; 100 ml of water are added and the aqueous phase is separated of The ethyl acetate solution is washed twice using 50 ml of water each time, dried over sodium sulfate and filtered, and the solvent is evaporated off. The oil that remains is purified by column chromatography over silica gel (tetrahydrofuran:hexane = 1:1). After the eluant mixture has been evaporated off, the initially brown oil is crystallised by trituration with petroleum ether (50-70C) and recrystallised from hexane/-dichloromethane. The beige-coloured crystals melt at 108-110C.
The following compounds can be prepared in an analogous manner:
-~
20326~3~
Table 1: Compounds of formula Ql = 2-furan R2 Q2 = 3-furany _~ CN Q3 = 2-thienyl Rl S C--NH- CH R3 Q4 = 3-thienyl O CP.= cyclopropyl Comp Rl ~~- R2 R3 Physical F~ ~ I I I const3nt 2 -CH3 CP. Q4 m.p. 108-110C
3 -C2Hs CP. Q3 m.p. 116-117C
4 H . -CH20CH3 Q4 56 HP. CP Q4 m.p. 93-95C
7 CP . -CH2OCH3 Ql 8 -CH3 CP. Ql m.p. 67-68C
9 -CH20CH3 CP. Q4 m.p. 135-136.5C
-C2Hs -CH20CH3 Q4 .
11 CP. H Q4 12 -C ~3 CP. Q2 m.p. 91-93~C
CP. -CH3 Ql 16 CP. -CH2OCH3 Q4 18 -CH3 CP. Q3 m.p. 135-136C
''' ~ , ' ~
203268%
Com~ l~ Rl R2 R3 Physical No constant 19 -C2Hs -CH2Oc2Hs Ql cyclobutyl -CH3 Q4 22 -CH3 cyclobutyl Q4 23 -CH2OC2Hs CP. Q4 24 CP. -CH3 Q4 m.p. 132-134C
-C2Hs -CH2Oc2Hs Q4 26 CP. -CH20C~F2 Q3 27 -CH3 -CH2OCH3 Ql 29 cyclohexyl -CH3 Q4 -CH2Oc2Hs -CH2OCH3 Ql 31 CP. -CH3 Q2 32 -CH3 -CH2OCH3 Q3 m.p. 77-81C
33 CP. -CH2OC2Hs Ql 34 -C3H7-n CP. Q4 m.p. 114-115C
-CH2OCH3 ~ -CH3 Ql m.p. 80-81 C
36 -CH2Oc2Hs H Q4 39 CP. -CH3 Q3 m.p. 127-130C
41 -CH2OC2Hs -CH2OCH3 Q4 42 CP. -CH2OC2Hs Q4 43 -CH2OCHF2 . _ .. . .
' : -203~68~:
_ Comp Rl R2 R3 Physical No. constant _ 44 -C3H7-n -CH2OCH3 Q4 c~ -CH2OCH3 Q4 47 -CH2OCH2CH2OCH3 CP. Q4 48 -CH2OCH3 -CH3 Q2 m.p. 79-80C
49 -CH3 . -CH2OCH3 Q4 -CH2OCH2CH-C~2 -CH3 Q4 c~3 51 ~ -CH2OCH3 Q4 52 :-CH2OCH2CF3 H Q4 53 -CH3 -CH2Oc2Hs : Ql 54 -CH2OCH3 -CH3 ~ Q3 m.p. 96-98C
-C3H7-iso CP. Q4 m.p. 132-133C
56 ~ -CH3 Q4 57 ~3 CP. Q4 59 -CH3 -CHzOC2H5 Q4 , . :. :, . .. - ~ ., ~ . . .:
:, ~ . , , . -: : ' .:
::
.,: .: , -203~6 Comp Rl R2 R3 Physical No. constant .
61 ~CH2 ~ -CH3 Q4 63 -cH2occH3F2 CP. Q4 64 --b -CH20CH3 Q
CP ~C2Hs Ql 66 SCH3 -CH20C3H7-iso Q4 67 ~ -CH3 Ql 68 -CH20CH3 -CH3 Q4 m.p. 111-113C
69 ~U20~F -CH3 ~ ~ Q4 -CH20 H5 -CH3 Ql 71 ~ -CH20CH3 Q4 73 -CH3 -CH20CHF2 Ql 74 ~ -CH3 Q3 -C3H7-iso -CH20C2Hs Q4 . . , ~ . .
- ' . ' .
Z0~26~3 Comp. Rl R2 R3 Physical No. constant 76 _CH20CH2 ~3 -CH3 Q4 77 CP. -C2Hs Q4 m.p. 116-117.~C
78 -C2H5 CP. Q2 m.p. 84-86C
79 -CH20C2Hs -CH3 Q2 ~ -CH3 Q2 81 -c4H9-n CP. Ql 82 ~ -CH2OC2Hs Ql 1 85 I H~ l ~ I Q4 86 CP. CP. Ql m.p. 86-88C
87 ~ H3 -CH3 Q4 89 -CH2OCH2CF3 CP. Q4 90 -C2Hs CP. Q4 m.p. 81-83C
:`
. ~` .
Z03~682 Comp Rl R2 ~ R3 - Physical No. constant -- SCH3 ,.
91 ~ -CH2Oc2Hs Q4 92 -C4Hg-n CP. Q4 93 -CH2Oc2Hs -CH3 Q3 n25 1.5723 94 -C2Hs CP. Ql m.p. 73-75C
-CH2OCH3 CP. Ql m.p. 81-83C
96 -CH2OC2Hs -CH3 Q4 97 -C2Hs -CH2O
98 -CH2OCHF2 -CH3 Ql 100 ~ -C2Hs Q4 101 -CH2OCHF2 ~C2Hs Q4 io2 ~ -CH3: Q4 103 CH2OcH2cH2OcH3 -CH3 Ql 104 -CH2OCH3 -C2Hs Q4 m.p. 111-112C
106 -CH2OCH2CF3 -C2Hs Q4 107 CP. -C3H7-iso Q4 m.p. 108-111C
108 -CH2OCHF2 -C3H7-iso 109 -CH20C2Hs -C2Hs .. ' ', ~'` ,' ' ', ' .
2032G~3 Comp Rl - -~ R3 PhYsStiCnt 110 -CH20CHF2 -CH3 Q2 oil 111 -CH20C2Hs -C2Hs Q4 m.p. 126-129C
112 --b -C3H7-n Q4 113 -CH20CH3 -C3H7-iso Q 4 114 -CH20CHF2 -C3H7-iso Q4 115 cH2oCH2cH2cH3 -C2Hs Q4 116 -CH20C2Hs -C3H7-iso Q4 . , ., -;~ . . ... .
', ' 203~
Comp Rl R2 R3 Physical No. constant _ 118 -CH2Oc2Hs -C2Hs . Q3 m.p. 96-97C
119 -CH2OCH3 -C2Hs Q3 m.p. 78-83C
120 CP. -C2Hs Q3 m.p. 106-109C
121 -CH2OCH3 CP. Q3 m.p. 104-106C
122 -CH2OCH3 ~C2Hs Q2 m.p. 81-83C
123 -CH2OCH3 CP. Q2 m.p. 105-106C
124 -CH2OCH3 -C2Hs Ql m.p. 104-105C
125 -C3H7iso CP. Ql m.p. 89-92C
126 -C3H7iso . CP. Q3 m.p. 12g-131C
127 -C3H7iso CP. Q2 m.p. 109-110C
128 -c3H7n CP. Ql m.p. 86-87C
129 -c3H7n CP. Q3 m.p. 74-76C
130 -C3H7n CP. Q2 m.p. 81-83C
132 -CH2OCHF2 C2Hs Ql 133 -CH2OCHF2 C2Hs Q2 134 -CH2OCHF2 C2Hs Q3 135 -CH2OCHF2 CP. Ql 136 -CH2OCHF2 CP. Q2 137 -CH2OCHF2 CP. __ 203~G~
_ . . __ Comp Rl R2 R3 Physical No. constant _ _ ._ ..
138 CP~ CP. . Q2 m.p. 103-105C
13g CP. CP. Q3 m.p. 123-126C
140 CP. -C3H7-n Ql m.p. 106-108C
141 CP. -C3H7iso Q2 m.p. 108-110C
142 CP. -C3H7iso Ql m.p. 97-100C
143 -CH2OCH3 -C3H7iso Q3 m.p. 89-91C
144 CP. -C3H7-n Q2 m.p. 111-114C
145 CP. . -C3H7iso Q3 m.p. 101-103C
146 -CH2Oc2Hs ~ CP. Ql m.p. 116-118C
147 -CH2OCH3 -C3H7-n Q3 m.p. 98-101C
148 -cH2oc2Hs CP. Q3 m.p. 123-125C
149 -CH2OCH3 -C3H7iso Ql m.p. 87-90C
150 -CH2OCH3 -C3H7-n Ql m.p. 91-94C
151 CP. -C3H7-n Q3 m.p. 103-106C
152 -CH2OCH3 -C3H7-n Q2 m.p. 85-87C
153 -CH2OCH3 -C3H7iso Q2 m.p. 93-95C
154 CP. -C3H7-n Q4 m.p. 114-120C
155 -CH2OCH3 -C3H7-rl Q4 m.p. 124-126C
156 -CH2OC2Hs CP. Q2 m.p. 109-111C
203;~
Table 2: Intermediates of fo~nula V
_ ~ CP.= cyclopropyl R~ S COOH
Comp Rl R2 ~---~ Physical No. constant 2.1 CP. CH3 m.p. 198-200C
2~2 CP. C2Hs m.p. 96-97C
2.3 CP. C3H7-n m.p. 104-106C
2.4 CP. . C3H7-iso m.p. 84-87C
2.5 CH3 CP. m.p. 190-191C
2.6 C2Hs CP. m.p. 158-159C
2.7 C3H7-iso CP. m.p. 122-123C
2.8 C3H7-n CP. m.p. 161-162C
2.9 -CH2OCH3 CH3 m.p. 168-169.5C
2.10 -CH2OCH3 C2Hs m.p. 146-147C
2.11 -CH2OCH3 CP. m.p. 159-161C
2.12 -CH2OC2Hs CH3 m.p. 185-186C
2.13 -CH2OC2Hs C2Hs m.p. 114-115C
2.14 -CH2OC2Hs CP. m.p. 132-134C
2.15 CP. CP. m.p. 102-104C
2.16 -CH2OCHF2 CH3 2.17 -CH2OCHF2 C2Hs 2.18 -CH2OCHF2 CP.
2.19 -CH2OCH3 C3H7-n m.p. 137-139C
2.20 -CH2OCH3 C3H7-iso m.p. 148 151C
20326?~3~
In the presence of an acid catalyst, such as HCl, it is readily possible to obtain the corresponding carboxylic acid Cl-C6alkyl esters from the acids of Table 2 by esterification with methanol, ethanol or one of the isomeric alcohols propanol, pentanol and hexanol.
2.Formulation Examples for active ingredients of formula I (throu~ehout percenta~es are bv wei~ht) 2.1. Wettable powder a) b) c) acompoundofTable 1 25 % 50% 75 %
sodium lignosulfonate 5 % 5 %
sodiumlaurylsulfate 3 % - 5 %
sodium diisobutylnaphthalenesulfonate - 6 % 10 %
octylphenol polyethylene glycol ether - 2 %
(7-8 moles of ethylene oxide) highly dispersed silicic acid 5 % 10 % 10 %
kaolin 62 % 27 %
The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspensions of the desired concentration.
2.2. Emulsifiable concentrate a compound of Table 1 10 %
octylphenol polyethylene glycol ether 3 %
(4-5 moles of ethylene oxide) calcium dodecylbenzenesulfonate 3 %
cyclohexanone 34 %
xylene mixture 50 %
Emulsions of any required concentration can be produced from this concentrate bydilution with water.
2.3. Dusts a) b) a compound of Table 1 5 % 8 %
talcum 95 %
kaolin - 92 %
.
, . , , , ,,: -~ . .
': , ' . ': ! ~ ~
` ~ .
- 29 - Z03Z68~:
Ready-for-use dusts are obtained by mixing the active ingredient with the carrier, and grinding the mixture in a suitable mill.
2.4. Extruder granulate a compound of Table 1 10 %
sodium lignosulfonate 2 %
carboxymethylcellulose 1 %
kaolin 87 %
The active ingredient is mixed and ground with the adjuvants, and the mixture ismoistened with water. The mixture is extruded and subsequently dried in a stream of air.
2.5 Coa~ranu!ate a compound of Table 1 3 %
polyethylene glycol (mol. wt. 200) 3 %
kaolin 94 %
The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granulates are obtained in this manner.
2.6. Suspension concentrate a compound of Table 1 40 %
ethylene glycol 10 %
nonylphenol polyethylene glycol ether 6 %
(15 moles of ethylene oxide) sodium lignosulfonate 10 %
carboxymethylcellulose 1 %
37% aqueous formaldehyde solution 0.2 %
silicone oil in the form of a 75%
aqueous emulsion 0.8 %
water 32 %
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired concentration can be .
203~6?3~:
obtained by dilution with water.
3~ Biolo~ical Examples I. Action against Phvtophthora infestans on tomato plants a) Curative action After a cultivation period of 3 weeks, tomato plants of the "Roter Gnom" varietyare sprayed with a zoospore suspension of the fungus and incubated in a cabinet at 18 to 20 and saturated humidity. The humidification is discontinued after 24 hours. When the plants have dried, they are sprayed with a mixture containing a wettable powder formulation of the test compound in a concentration of 600, 200 or 60 ppm. When the spray-coating has dried, the plants are returned to the humidity cabinet for four days. The effectiveness of the test compounds is evaluated on the basis of the number and size of the typical leaf specks occurring after that time.
b) Preventive svstemic action A wettable powder forrnulation of the test compound is applied in a concentration of 60 ppm (based on the volume of the soil) to the surface of the soil of three-week-old tomato plants of the "Roter Gnom" variety in pots. After three days theunderside of the leaves of the plants are sprayed with a zoospore suspension of Phytophthora infestans. The plants are then kept in a spraying cabinet at 18 to 20C and saturated humidity for 5 days. The effectiveness of the test compounds is evaluated on the basis of the number and size of the typical leaf specks that form after that tirne.
.
The following compounds of Table 1 inhibit disease attack to less than 10 %: Nos. 2,3,5, 8,9,12,18,24,32,34,35,39,48,54,55,63,68,77,78,90,93,95,98,104,107,110, 111, 113, 116, 118 to 130 and 138 to 156.
II. Action a~ainst Plasmopara viticola (Bert.et Curt.) (Berl. et DeToni) on vines a) Residual preventive action Vine cuttings of the "Chasselas" variety are raised in a greenhouse. In the 10-leaf stage, 3 plants are sprayed with a mixture prepared from a wettable powder ,. - :; ,:
'~ ' ' ' , 203Z6?3~, formulation of the test compound (200 ppm of active ingredient). After the spMy-coating has dried, the undersides of the leaves of the plants are uniforrnly infected with a spore suspension of the fungus. The plants are then kept in a humidity chamber for 8 days. After this time the control plants exhibit clear symptoms of disease. The effectiveness of the test compounds is evaluated on thebasis of the number and size of the infection sites on the treated plants.
b) Curative action Vine cuttings of the "Chasselas" variety are raised in a greenhouse and in the 10-leaf stage the undersides of the leaves are infected with a spore suspension of Plasmopara viticola. After 24 hours in a humidity chamber the plants are sprayedwith an active ingredient mixture prepared from a wettable powder formulation ofthe test compound (500 ppm of active ingredient). The plants are then kept in the humidity cabinet for a further 7 days. After this time the control plants exhibit clear symptoms of disease. The effectiveness of the test compounds is evaluated on the basis of the number and size of the infection sites on the treated plants.
In this test too, all the compounds mentioned in Example 1 inhibit disease attack to less than 10 %.
m. Action against Pvthium debaryanum on su~ar beet (Beta vul~aris) a) Action after soil apRlication The fungus is cultured on sterile oat grains and added to a soiVsand mixture. The infected soil is introduced into pots and sown with sugar beet seeds. Immediately after sowing, wettable powder formulations of the test compounds in the form of aqueous suspensions are poured onto the soil (20 ppm of active ingredient, basedon the volume of the soil). The pots are then placed in a greenhouse at 20-24C for 2-3 weeks. The soil is kept constantly uniformly wet by lightly spraying with water. The test is evaluated by determining the emergence rate of the sugar beetplants and the proportion of healthy and diseased plants.
b) Action after dressin~
The fungus is cultured on sterile oat grains and added to a soiVsand mixture. The infected soil is introduced into pots and sown with sugar beet seeds that have been dressed with a dressing powder formulation of the test compounds (1000 ppm of Z03~fi?3~
active ingredient, based on the weight of the seeds). The pots are placed in a greenhouse at 20-24C for 2-3 weeks. The soil is kept uniformly wet by lightly spraying with water. The test is evaluated by determining the emergence rate of the sugar béet plants and the proportion of healthy and diseased plants.
An emergence rate of more than 80 % is obtained with compounds of Table 1. The corresponding control plants exhibit an emergence rate of less than 30 % and have an unhealthy appearance.
Claims (23)
1. Thiazolyl-5-carbonamide derivatives of formula I and acid addition salts and metal salt complexes thereof (I) wherein R3 is 2-furanyl, 2-thienyl, 3-furanyl or 3-thienyl; and wherein R1 and R2 each independently of the other have the following meanings:
a) C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio,b) the group -CH2-X-R4, and c) one of the two substituents R1 and R2 may also be hydrogen or C1-C4alkyl, wherein X is oxygen or sulfur, and R4 is C1-C4alkyl that may be unsubstituted or substituted by halogen or, in the case of C2-C4alkyl, also by C1-C3alkoxy, or wherein R4 is C3-C4alkenyl, C3-C4alkynyl or a phenyl group or benzyl group of which the aromatic ring is unsubstituted or may be substituted by halogen, C1-C2alkyl, C1-C2alkoxy, CF3 or by NO2.
a) C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio,b) the group -CH2-X-R4, and c) one of the two substituents R1 and R2 may also be hydrogen or C1-C4alkyl, wherein X is oxygen or sulfur, and R4 is C1-C4alkyl that may be unsubstituted or substituted by halogen or, in the case of C2-C4alkyl, also by C1-C3alkoxy, or wherein R4 is C3-C4alkenyl, C3-C4alkynyl or a phenyl group or benzyl group of which the aromatic ring is unsubstituted or may be substituted by halogen, C1-C2alkyl, C1-C2alkoxy, CF3 or by NO2.
2. Compounds of formula I according to claim 1, wherein one of the two substituents R1 and R2 is C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio, and the other substituent is d) cyclobutyl, cyclopropyl, methylcyclopropyl or methylthiocyclopropyl, e) the group -CH2-X-R4 or f) hydrogen or C1-C4alkyl, while R3, X and R4 are as defined above.
3. Compounds of formula I according to claim 2, wherein one of the two substituents R
and R2 is C3-C6cycloalkyl and the other is cyclobutyl or cyclopropyl, while R3 is as defined above.
and R2 is C3-C6cycloalkyl and the other is cyclobutyl or cyclopropyl, while R3 is as defined above.
4. Compounds of formula I according to claim 3, wherein R1 and R2 are cyclopropyl.
5. Compounds of formula I according to claim 2, wherein R1 is hydrogen, C1-C4alkyl or the group -CH2-X-R4, X is oxygen or sulfur, and R4 is C1-C4alkyl that is unsubstituted or substituted by fluorine or, in the case of C2-C4alkyl, may also be substituted by C1-C3alkoxy; or wherein R4 is allyl, propargyl, phenyl or benzyl, the aromatic rings of the latter radicals being unsubstituted or substituted by one or two of the substituents fluorine, chlorine, methyl, ethyl, methoxy and CF3, while R2 is C3-C6cycloalkyl that is unsubstituted or substituted by methyl or methylthio, while R3 is as defined above.
6. Compounds according to claim 5, wherein X is oxygen.
7. Compounds according to claim 6, wherein R1 is hydrogen, C1-C4alkyl or -CH2-O-R4, R2 is cyclobutyl, cyclopropyl, methylcyclopropyl or methylthiocyclopropyl, and R4 is C1-C4alkyl that is unsubstituted or fluoro-substituted or, in the case of C2-C4alkyl, may also be substituted by methoxy or ethoxy; or wherein R4 is allyl, propargyl, phenyl, chlorophenyl, fluorophenyl, benzyl, chlorobenzyl or fluorobenzyl, while R3 is as defined above.
8. Compounds according to claim 7, wherein R2 is cyclopropyl, and R4 is methyl, ethyl, fluoromethyl, difluoromethyl, trifluoroethyl, allyl, propargyl, phenyl or benzyl.
9. Compounds according to claim 8, wherein R1 is hydrogen, C1-C3alkyl, methoxymethyl or ethoxymethyl.
10. Compounds of formula I according to claim 1, wherein one of the two substituents R
and R2 is the group -CH2-X-R4 and the other substituent is hydrogen, C1-C4alkyl or -CH2-X-R4, X is oxygen or sulfur, R3 is as defined above, and R4 is C1-C4alkyl that is unsubstituted or substituted by fluorine or, in the case of C2-C4alkyl, may also be substituted by C1-C3alkoxy; or wherein R4 is allyl, propargyl, phenyl or benzyl, the aromatic rings of the latter radicals being unsubstituted or substituted by one or two of the substituents fluorine, chlorine, methyl, ethyl, methoxy and CF3.
and R2 is the group -CH2-X-R4 and the other substituent is hydrogen, C1-C4alkyl or -CH2-X-R4, X is oxygen or sulfur, R3 is as defined above, and R4 is C1-C4alkyl that is unsubstituted or substituted by fluorine or, in the case of C2-C4alkyl, may also be substituted by C1-C3alkoxy; or wherein R4 is allyl, propargyl, phenyl or benzyl, the aromatic rings of the latter radicals being unsubstituted or substituted by one or two of the substituents fluorine, chlorine, methyl, ethyl, methoxy and CF3.
11. Compounds according to claim 10, wherein R1 is the group -CH2-O-R4, R2 is hydrogen, C1-C4alkyl or -CH2-O-R4, R3 is as defined above, and R4 is C1-C4alkyl that is unsubstituted or substituted by fluorine, methoxy or by ethoxy, or wherein R4 is allyl, propargyl, phenyl, chlorophenyl, fluorophenyl, benzyl, chloro-benzyl or fluorobenzyl.
12. Compounds according to claim 11, wherein R2 is hydrogen or C1-C3alkyl.
13. Compounds of formula I according to claim 1, wherein either a) R1 is CH3, C2H5, n-propyl, isoC3H7, CH2-O-CH3, Ch2-O-C2H5, CH2-O-CHF2 or cyclopropyl, and R2 is cyclopropyl, or wherein b) R1 is CH2-O-CH3, CH2-O-C2H5, CH2-O-CHF2 or cyclopropyl and R2 is C1-C3-alkyl, and R3 is as defined above.
14. Compounds of formula I according to claim 13, wherein R1 is methyl, ethyl, n-propyl or isopropyl and R2 is cyclopropyl.
15. Compounds of formula I according to claim 13, wherein R1 is CH2-O-CH3, CH2-O-C2H5 or cyclopropyl and R2 is methyl, ethyl, n-propyl, isopropyl or cyclopropyl.
16. A process for the preparation of thiazolyl-5-carbonamide derivatives of formula I
according to claim 1, which comprises reacting the thiazolyl-5-carboxylic acid of formula V
(V) or an acid halide, an ester or an acid anhydride thereof, with an aminoacetonitrile of formula II
(II) in the presence or absence of a condensation agent or an acid acceptor, the substituents R1, R2 and R3 being as defined under formula I.
according to claim 1, which comprises reacting the thiazolyl-5-carboxylic acid of formula V
(V) or an acid halide, an ester or an acid anhydride thereof, with an aminoacetonitrile of formula II
(II) in the presence or absence of a condensation agent or an acid acceptor, the substituents R1, R2 and R3 being as defined under formula I.
17. A microbicidal composition for the control of plant diseases containing as active ingredient a compound of formula I according to claim 1 together with a suitable carrier.
18. A composition according to claim 17 containing as active ingredient a compound according to any one of claims 2 to 15.
19. The use of a compound of formula I for controlling microorganisms and for preventing attack by microorganisms.
20. A method of controlling plant diseases or preventing attack by disease, which comprises the application of a compound of formula I to the plants, to their growing site, to parts of the plants or to plant propagation material.
21. A method according to claim 20, wherein the propagation material is seed.
22. Compounds of formula V
(V) and C1-C6carboxylic acid esters thereof, wherein R1 and R2 are as defined under formula I
according to claim 1.
(V) and C1-C6carboxylic acid esters thereof, wherein R1 and R2 are as defined under formula I
according to claim 1.
23. Compounds of formula V and C1-C6carboxylic acid esters thereof according to claim 22, wherein R1 and R2 are as defined under formula I according to claim 13.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH458089 | 1989-12-21 | ||
| CH4580/89-0 | 1989-12-21 | ||
| CH342590 | 1990-10-26 | ||
| CH3425/90-0 | 1990-10-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2032682A1 true CA2032682A1 (en) | 1991-06-22 |
Family
ID=25692971
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002032682A Abandoned CA2032682A1 (en) | 1989-12-21 | 1990-12-19 | Pesticidal compositions |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0434620A3 (en) |
| JP (1) | JPH04117380A (en) |
| KR (1) | KR910011815A (en) |
| CN (1) | CN1028477C (en) |
| AU (1) | AU638082B2 (en) |
| BG (1) | BG61035B1 (en) |
| BR (1) | BR9006522A (en) |
| CA (1) | CA2032682A1 (en) |
| EG (1) | EG19091A (en) |
| HU (1) | HUT55961A (en) |
| IE (1) | IE904629A1 (en) |
| IL (1) | IL96721A (en) |
| MA (1) | MA22022A1 (en) |
| NZ (1) | NZ236532A (en) |
| PT (1) | PT96249B (en) |
| YU (1) | YU239790A (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5514643A (en) * | 1993-08-16 | 1996-05-07 | Lucky Ltd. | 2-aminothiazolecarboxamide derivatives, processes for preparing the same and use thereof for controlling phytopathogenic organisms |
| JP4521617B2 (en) * | 1995-03-31 | 2010-08-11 | 日本農薬株式会社 | Agricultural and horticultural disease control agent and method of use thereof |
| KR20000021443A (en) * | 1998-09-29 | 2000-04-25 | 성재갑 | Method for preparing 2-aminothiazole carboxamide derivatives |
| KR100426179B1 (en) * | 2000-05-10 | 2004-04-03 | 주식회사 엘지생명과학 | Novel fungicidal compositions containing N-(α-cyano-2-thenyl)-4-ethyl-2-(ethylamino)-5-thiazolecarboxamide |
| KR100420758B1 (en) * | 2000-11-23 | 2004-03-02 | 주식회사 엘지생명과학 | Photostabilized Fungicide That Contains Ethaboxam and its Photostabilizer, Method for Fungicidal Use and Method for Increasing Photostability of Ethaboxam |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3851004T2 (en) * | 1987-05-26 | 1995-01-26 | Sumitomo Chemical Co | Amide derivatives, their manufacture and agricultural fungicides containing them. |
| US4980363A (en) * | 1987-10-23 | 1990-12-25 | Mitsui Toatsu Chemicals, Inc. | Novel amide derivatives, processes for production thereof, and agricultural-horticultural fungicide containing them |
| AU3800689A (en) * | 1988-07-15 | 1990-01-18 | Sumitomo Chemical Company, Limited | Amide derivatives, and their production and agricultural and horticultural fungicides containing them |
-
1990
- 1990-12-12 EP EP19900810979 patent/EP0434620A3/en not_active Ceased
- 1990-12-19 NZ NZ236532A patent/NZ236532A/en unknown
- 1990-12-19 IL IL9672190A patent/IL96721A/en not_active IP Right Cessation
- 1990-12-19 YU YU239790A patent/YU239790A/en unknown
- 1990-12-19 CA CA002032682A patent/CA2032682A1/en not_active Abandoned
- 1990-12-19 PT PT96249A patent/PT96249B/en not_active IP Right Cessation
- 1990-12-20 MA MA22297A patent/MA22022A1/en unknown
- 1990-12-20 EG EG75190A patent/EG19091A/en active
- 1990-12-20 AU AU68347/90A patent/AU638082B2/en not_active Ceased
- 1990-12-20 HU HU908363A patent/HUT55961A/en unknown
- 1990-12-20 BR BR909006522A patent/BR9006522A/en not_active Application Discontinuation
- 1990-12-20 IE IE462990A patent/IE904629A1/en unknown
- 1990-12-21 KR KR1019900021692A patent/KR910011815A/en not_active Application Discontinuation
- 1990-12-21 JP JP2413411A patent/JPH04117380A/en active Pending
- 1990-12-21 BG BG93515A patent/BG61035B1/en unknown
- 1990-12-21 CN CN90106047A patent/CN1028477C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| IL96721A0 (en) | 1991-09-16 |
| MA22022A1 (en) | 1991-07-01 |
| IE904629A1 (en) | 1991-07-17 |
| IL96721A (en) | 1995-06-29 |
| BR9006522A (en) | 1991-10-01 |
| PT96249B (en) | 1998-06-30 |
| AU6834790A (en) | 1991-06-27 |
| BG61035B1 (en) | 1996-09-30 |
| YU239790A (en) | 1993-05-28 |
| EP0434620A3 (en) | 1992-01-08 |
| NZ236532A (en) | 1993-03-26 |
| JPH04117380A (en) | 1992-04-17 |
| HUT55961A (en) | 1991-07-29 |
| PT96249A (en) | 1991-09-30 |
| EG19091A (en) | 1994-04-30 |
| CN1028477C (en) | 1995-05-24 |
| KR910011815A (en) | 1991-08-07 |
| CN1052675A (en) | 1991-07-03 |
| AU638082B2 (en) | 1993-06-17 |
| BG93515A (en) | 1993-12-24 |
| EP0434620A2 (en) | 1991-06-26 |
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