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WO1996017843A2 - Novel pyrimidinyloxy- and pyrimidinylamino-ethylphenyl-dioxolane derivatives - Google Patents

Novel pyrimidinyloxy- and pyrimidinylamino-ethylphenyl-dioxolane derivatives Download PDF

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Publication number
WO1996017843A2
WO1996017843A2 PCT/EP1995/004795 EP9504795W WO9617843A2 WO 1996017843 A2 WO1996017843 A2 WO 1996017843A2 EP 9504795 W EP9504795 W EP 9504795W WO 9617843 A2 WO9617843 A2 WO 9617843A2
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Prior art keywords
formula
alkyl
compound
alkoxy
phenyl
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PCT/EP1995/004795
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French (fr)
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WO1996017843A3 (en
Inventor
Clemens Lamberth
Fritz Schaub
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Novartis Ag
Novartis-Erfindungen Verwaltungsgesellschaft M.B.H.
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Application filed by Novartis Ag, Novartis-Erfindungen Verwaltungsgesellschaft M.B.H. filed Critical Novartis Ag
Priority to EP95941073A priority Critical patent/EP0796259A2/en
Priority to BR9509877A priority patent/BR9509877A/en
Priority to MX9703363A priority patent/MX9703363A/en
Priority to JP8517320A priority patent/JPH10512236A/en
Priority to AU42602/96A priority patent/AU4260296A/en
Publication of WO1996017843A2 publication Critical patent/WO1996017843A2/en
Publication of WO1996017843A3 publication Critical patent/WO1996017843A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/78—Benzoic acid esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
    • C07D317/20—Free hydroxyl or mercaptan
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
    • C07D317/22—Radicals substituted by singly bound oxygen or sulfur atoms etherified
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
    • C07D317/24—Radicals substituted by singly bound oxygen or sulfur atoms esterified
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/28—Radicals substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • the present invention relates to novel 2-[4-(2-(2-pyrimidin-4-yloxy-and -4-ylamino)-ethyl)-phenyl]-dioxolanes, the synthesis thereof, and the use of said compounds for controlling undesired acarinae, fungi, and insects.
  • R 1 is hydrogen, C 1-4 alkyl, C 1-4 haloalkyl or C 3-6 cycloalkyl,
  • R 2 is hydrogen, C 1-10 alkyl, C 1-8 alkoxy-C 1 _ 4 alkyl, C 3 . 8 alkenyloxy-C 1-4 alkyl,
  • R 3 and R 4 independently are halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkoxy-C 1-4 alkyl,
  • Z is NH or oxygen
  • the compounds of formula I exhibit strong pesticidal activity, especially strong acaricidal, fungicidal, and insecticidal activities.
  • the compounds of formula I are suitable for controlling plant pests of the orders of acarines and of insects. Further, the compounds of formula I provide fungicidal activity against phytopathogenic fungi.
  • alkyl is understood to encompass straight-chain and branched alkyl groups, with straight-chain and lower alkyl being preferred.
  • alkyl are methyl, ethyl, n-propyl, i-propyl, n-butyl, sec.-butyl, tert. butyl, i-butyl, and the isomeric forms of pentyl, hexyl, heptyl, octyl, nonyl or decyl.
  • Cycloalkyl designates cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • Alkoxy for example encompasses methoxy, ethoxy, n-propoxy, i-propoxy, n-butyloxy, sec. butyloxy, tert. butyloxy, i-butyloxy and the isomeric forms of pentyloxy, hexyloxy, heptyloxy, or octyloxy.
  • Halogen designates fluorine, chlorine, bromine and iodine, with fluorine and chlorine being preferred.
  • Alkenyloxy for example designates allyloxy, methallyloxy, 2-butenyloxy, 3-butenyloxy and the isomeric forms of pentenyloxy, hexenyloxy, heptenyloxy, or octenyloxy.
  • Alkynyloxy designates for example propargyloxy
  • Aryl stands for an aromatic hydrocarbon radical, for example phenyl or naphthyl, with phenyl being preferred.
  • Aryloxy designates an aryl radical being bounded through an oxygen atom. Examples are phenoxy, ⁇ -naphthyloxy or
  • Heteroaryloxy stands for an aromatic 5- to 6-membered cyclic radical comprising one, two or three atoms being selected from nitrogen, oxygen or sulfur, and being bounded through an oxygen atom.
  • the heteroaryl group of heteroaryloxy groups may also be in condensed form with another heteroaryl radical or an aryl radical.
  • Cyanoalkyl designates an alkyl group being substituted with one or two cyano groups, with one cyano group being preferred. Examples are cyanomethyl, 1-cyanoethyl, 2-cyanoethyl and the isomers of cyanopropyl or cyanobutyl.
  • Alkoxycarbonyl designates for example methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butyloxycarbonyl, sec-butyloxycarbonyl, tert. butyloxycarbonyl or i-butyloxycarbonyl.
  • R 3 and R 4 together form a bridge member the pyrimidinyl ring forms a part of a condensed bicyclic ring system.
  • Such bicyclic ring systems are for example quinazoline, tetrahydroquinazoline, thieno[2,3-d]pyrimidine or thieno[3,2-d]pyrimidine.
  • haloalkyl designates an alkyl group being mono- to perhalogenated.
  • examples are trifluoromethyl, difluoromethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, chloromethyl, fluoromethyl, and the like.
  • Alkoxyalkyl for example designates methoxy methyl, ethoxymethyl, propoxymethyl, ethoxyethyl, methoxyethyl, butyloxymethyl, isopropoxymethyl, methoxypropyl, and the like.
  • Alkenyloxyalkyl is for example allyloxymethyl, methallyloxymethyl, allyloxyethyl, methallyloxyethyl, 2-butenyloxymethyl, and the like.
  • Haloalkenyloxyalkyl for example encompasses 2-chloroallyloxymethyl and the like.
  • Alkynyloxyalkyl for example designates propargyloxymethyl or propargyloxyethyl. Haloalkoxyalkyl for example is
  • Alkylthioalkyl encompasses for example methylthiomethyl or ethylthiomethyl.
  • Examples for aryloxyalkyl are 4-chlorophenoxymethyl, phenoxymethyl or 2-methoxyphenoxymethyl.
  • Examples for arylalkoxyalkyl are benzyloxymethyl or methylbenzyloxymethyl.
  • Examples for heteroaryloxyalkyl are pyrazolyloxymethyl or pyrimidinyloxymethyl.
  • alkoxyalkoxyalkyl are methoxy ethoxymethyl, ethoxyethoxymethyl or propoxy ethoxymethyl.
  • Examples for alkoxycarbonylalkyl are methoxycarbonylmethyl or ethoxycarbonylmethyl.
  • Examples for arylalkyl are benzyl, phenethyl, 1-phenylethyl, phenylpropyl, phenylbutyl or the like.
  • the compounds of formula I contain one or more asymmetrical carbon atoms. These compounds may therefore exist in optical pure form or in mixtures of the isomeric forms. Where optically pure forms are intended in this document they are mentioned specifically. In all other cases mixtures of the isomeric forms are intended, as e.g. obtained from the applied synthesis method. Where mixtures of isomers are obtained during synthesis, the pure isomers may be obtained from the mixtures by known separation techniques, such as crystallization, chromatography or destination, or by combined derivatisation/separation methods.
  • R 3 and R 4 together form an optionally substituted 1,4-butylene or butadienylene bridge, thus together with the pyrimidine ring to which they are attached form an optionally substituted tetrahydroquinazoline or quinazoline moiety, or b) R 1 is hydrogen or methyl, or c) R 2 is C 1-8 alkyl, C 1-8 alkoxy-C 1-4 alkyl, C 3-8 alkenyloxy-C 1-4 alkyl, or C 1-4 alkoxy- C 1-4 alkoxy-C 1-4 alkyl.
  • R 1 is hydrogen or methyl
  • R 2 is C 1-8 alkyl, C 1-8 alkoxy- C 1-8 alkyl, C 3-8 alkenyloxy-C 1-4 alkyl, or C 1-4 alkoxy-C 1-4 alkoxy-C 1-4 alkyl
  • R 3 and R 4 together form an optionally substituted 1 ,4-butylene or butadienylene bridge.
  • Preferred individual compounds of formula I are:
  • the compounds of formula I wherein Z is oxygen may be obtained by reacting a 2-[4-(2- hydroxyethyl)-phenyl]-dioxolane of formula II wherein R 1 and R 2 are as defined for formula I, with a 4-halopyrimidine of formula III
  • R 3 and R 4 are as defined for formula I, and Hal is halogen, preferably chlorine or bromine.
  • the reaction (II + III ⁇ I) may be carried out in a manner known per se for etherification methods.
  • the etherification is advantageously carried out in the presence of a base.
  • the reaction is carried out in the presence of an inert solvent.
  • the reaction temperature is in general between 0°C and the boiling temperature of the reaction mixture, preferably is between room temperature and the boiling temperatures of the solvents used.
  • suitable bases include alkaline metal hydrides such as sodium hydride, and alkaline metal hydroxides such as sodium hydroxide, potassium hydroxide.
  • ether formation is advantageously carried out in the presence of a phase transfer catalyst such as triethylbenzylammonium chloride or bromide (TEBA), tetrabutyl ammonium chloride, etc. and a suitable inert solvent like aromatic hydrocarbons such as benzene and toluene.
  • a phase transfer catalyst such as triethylbenzylammonium chloride or bromide (TEBA), tetrabutyl ammonium chloride, etc.
  • TEBA triethylbenzylammonium chloride or bromide
  • suitable inert solvent like aromatic hydrocarbons such as benzene and toluene.
  • suitable inert solvents are hydrocarbons such as toluenes, ethers such as diethyl ether, tetrahydrofuran and 1,2-dimethoxyethane; polar solvents such as
  • dimethylformamide or acetonitrile dimethylformamide or acetonitrile; and mixtures comprising two or more of them.
  • the desired end-product is isolated and purified according to known techniques, for example by evaporation of solvent, chromatography or crystallization.
  • the compounds of formula II may be obtained by hydrolysing a compound of formula IV
  • R 1 and R 2 are as defined for formula I and X is hydrogen, C 1-4 alkyl, C 1-4 alkoxy, halo, nitro or cyano, and Y is hydrogen, C 1-4 alkyl, C 1-4 alkoxy, halo or cyano, in the presence of a base.
  • the hydrolization reaction (IV ⁇ II) may be carried out in a manner known per se for alkaline hydrolization reactions of carboxylic acid esters.
  • the reaction is preferably carried out in the presence of a base.
  • the reaction is carried out in an aqueous solution, or in a mixture of water and an inert organic solvent.
  • Preferred such solvents are miscible with water, such as alcohols, e.g. methanol, ethanol or isopropanol, or are aromatic hydrocarbons such as toluene and xylene in which case, preferably, a phase transfer catalyst is being used.
  • a phase transfer catalyst is being used.
  • all types of inorganic bases may be used.
  • reaction temperatures are between 0°C and +100°C, preferably between +20°C and +50°C.
  • the compounds of formula IV may be obtained by acetalising a compound of formula V
  • R 1 , X and Y are as defined for formula IV with a glycol of formula VI
  • R 2 is as defined for formula I.
  • the reaction (V + VI ⁇ FV) corresponds to a standard acetalisation reaction, which may be conducted in the manner known per se for acetalisation reactions.
  • the reaction may be catalyzed in the presence of an organic acid or a strong inorganic acid such as cone, sulfuric acid, and the water resulting as one condensation product may be separated continuously from the reaction mixture by azeotropic destination.
  • the reactants of formula V and VI are solved in an inert solvent, suitable for azeotropic destination, e.g.
  • a suitable condenser e.g. a Dean-Stark trap.
  • the compounds of formula II may also be prepared by acetalising a compound of formula VII wherein R 1 , X and Y are as defined for formula IV with a glycol of formula VI wherein R 2 is as defined for formula I.
  • the acetalisation (VII + VI ⁇ II) may be conducted by a method similar to the described method for obtaining the compounds of formula IV from compounds of formula V and VI.
  • the compounds of formula V may be obtained by reacting a compound of formula VIII
  • R' 1 is C 1-4 alkyl, C 1-4 haloalkyl or C 3-6 cycloalkyl and L is chlorine or bromine.
  • the reaction (VIII + IX ⁇ V) corresponds to a standard acid-catalyzed Friedel-Crafts acylation.
  • the reaction is preferably carried out in the presence of a Lewis acid, like aluminium chloride or in the presence of a proton acid such as sulfuric acid.
  • a Lewis acid like aluminium chloride or in the presence of a proton acid such as sulfuric acid.
  • the reactants of formula VIII + IX are added to a suspension of a stochiometric amount of anhydrous aluminium chloride in a solvent, e.g. dichloromethane chloroform, nitrobenzene or carbon disulfide.
  • the reaction temperature is preferably between 0°C and +30°C.
  • the compounds of formula I whrein Z is NH may be obtained by reacting a 2-[4-(2-aminoethyl)-phenyl]-dioxolane of formula X whrein R 1 and R 2 are as defined as defined for formula I, with a 4-halopyrimidine of formula III
  • R 3 and R 4 are as defined for formula I, and Hal is halogen, preferably chlorine or bromine.
  • the reaction (X + IIl ⁇ I) may be carried out in a manner known per se for the reaction of amines with alkylhalides or heterocyclic halides, e.g. of 2-halopyridines or 2-, or 4-halopyrimidines.
  • the reaction is advantageously carried out in the presence of a base.
  • a base Preferably the reaction is carried out in an aqueous solution, or in a mixture of water and an inert organic solvent.
  • solvents which are miscible with water such as alcohols, e.g. methanol, ethanol or isopropanol, or are aromatic hydrocarbons such as toluene and xylene in which case, preferably, a phase transfer catalyst is being used.
  • inorganic bases may be used, appropriate are especially sodium hydroxide, potassium hydroxide, sodium carbonate, or potassium carbonate.
  • Reaction temperatures are between 0°C and +100°C, preferably between +50°C and +100°C.
  • the compounds of formula X may be obtained by hydrolising a compound of formula XI
  • R 1 and R 2 are as defined for formula I.
  • the hydrolization reaction (XI ⁇ X) may be carried out in a manner known per se for the hydrolysis of phthalimide derivatives.
  • the reaction is preferably carried out in the presence of an amine or hydrazine.
  • hydrazine, methylamine, ethylamine, propylamine, 2-propylamine, butylamine or pentylamine may be applied.
  • reaction is carried out in an aqueous solution, or in an inert organic solvent.
  • solvents are alcohols, such as methanol, ethanol or isopropanol.
  • Reaction temperatures are between 0°C and +100°C, preferably between +20°C and +50°C.
  • the compounds of formula XI may be obtained by converting a compound of formula XII
  • R 1 and R 2 are as defined for formula I and Hal is halogen, preferably chlorine or bromine with phthalimide.
  • the reaction (XII ⁇ XI) may be carried out in a manner known per se for the alkylation of amines.
  • the reaction is advantageously carried out in the presence of a base.
  • Preferably the reaction is carried out in an inert organic solvent.
  • the compounds of formula XII may be obtained by reacting a compound of formula II
  • reaction (II ⁇ XI) may be carried out in a manner known per se for the Mitsunobu reaction (O. Mitsunobu, Synthesis, 1981. p. 1 ff; and D.L. Hughes, Org. Reaction, 1982, Vol. 42, p. 395 ff). It is adventageously carried out in the presence of an organo-phosphorus compound, e.g. triphenylphosphine, tritolylphosphine or tributylphosphine and an azodicarboxylate, for instance diethyl azodicarboxylate or diisopropyl azodicarboxylate.
  • an inert organic solvent e.g. diethyl ether, dioxane or tetrahydrofuran.
  • the compounds of formula XII may be obtained by acetalising a compound of formula
  • R 2 is as defined for formula I.
  • the reaction (XIII + VI ⁇ XII) corresponds to standard acetalisation reaction, which may be conducted in the manner known per se for acetalisation reactions.
  • the reaction may be catalyzed in the presence of an organic acid or a strong inorganic acid such as cone, sulfuric acid, and the water resulting as one condensation product may be separated continuously from the reaction mixture by azeotropic destination.
  • the reactants of formula Xm and VI are solved in an inert solvent, suitable for azeotropic destination, e.g.
  • the compounds of formula I are effective against plant-damaging Arthropodae belonging to the order of Acarine, as well as to the class of Insects and against phytopathogenic fungi.
  • the compounds of formula I have an excellent plant tolerance.
  • the compounds of the invention are therefore indicated for treatment of plants, seeds and soil to combat phytopathogenic fungi, e.g. Basidiomycetes of the order Uredinales (rusts) such as
  • Puccinia spp Hemileia spp, Uromyces spp; and Ascomycetes of the order Erysiphales (powdery mildew) such as Erysiphe ssp, Podosphaera spp, Uncinula spp, Sphaerotheca spp; as well as Cochliobolus; Pyrenophora spp; Venturia spp; Mycosphaerella spp;
  • Leptosphaeria Leptosphaeria
  • Deuteromycetes such as Pyricularia, Pellicularia (Corticium), Botrytis
  • Oomycetes such as Phytophthora spp, Plasmopara spp.
  • a subgroup of compounds of formula I are particularly effective against powdery mildew and rust, Pyrenophora and Leptosphaeria fungi in particular against pathogens of monocotyledonous plants such as cereals, including wheat and barley .
  • Another subgroup of compounds of formula I are particularly effective against Oomycetes on dicotyledonous plants such as grapevine, tomatoes or potatoes.
  • the compounds of formula I are particularly useful for controlling insects, particularly black bean aphids (Aphis fabae), green rice leafhoppers (Nephotettix cincticeps), mustard beetles (Phaedon cochleariae), and mosquitos (Aedes aegypti).
  • This application therefore provides a method of controlling insects comprising applying to the insects or their locus an insecticidally effective amount of the compounds of formula I.
  • the compounds of formula I are particularly useful for controlling Acarina, especially the two-spotted spider mite (Tetranychus urticae) and the European red mite (Panonychus ulmi).
  • This application therefore provides a method of controlling Acarina comprising applying to the Acarina or their locus an acaricidally effective amount of the compounds of formula I.
  • the compounds of the formula I are employed in unaltered form, i.e., as a pure substance as obtained from the synthesis, dried and ground, or preferably together with the auxiliaries conventionally used in the art of formulation, and they can therefore be processed in a known manner for example to emulsion concentrates, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granules and also encapsulations in polymeric substances.
  • the application methods such as spraying, misting, atomizing, scattering or pouring, as well as the compositions, are selected to suit the intended aims and the prevailing circumstances.
  • the compounds of the invention may be used in a great number of crops, such as soybean, coffee, ornamentals (i.a. pelargonium, roses) vegetables (e.g. peas, cucumber, celery, tomato and bean plants), sugarbeet, sugarcane, cotton flax, maize (com), vineyards, pomes and stone fruits (e.g. apple, pears, prunes) and in cereals (e.g. wheat, oats, barley, rice).
  • crops such as soybean, coffee, ornamentals (i.a. pelargonium, roses) vegetables (e.g. peas, cucumber, celery, tomato and bean plants), sugarbeet, sugarcane, cotton flax, maize (com), vineyards, pomes and stone fruits (e.g. apple, pears, prunes) and in cereals (e.g. wheat, oats, barley, rice).
  • crops such as soybean, coffee, ornamentals (i.a. pelargonium, roses) vegetables (e.g.
  • the invention also provides acaricidal, fungicidal and insecticidal compositions, comprising as active ingredient a compound of formula I in association with an agriculturally acceptable diluent (hereinafter diluent). They are obtained in conventional manner, e.g. by mixing a compound of the invention with a diluent and optionally additional ingredients, such as surfactants.
  • diluent an agriculturally acceptable diluent
  • compositions, preparations or combinations, containing the active substance of the formula I or combinations of this active substance with other fungicides, insecticides or acaricides, and if desired a solid or liquid additive are prepared in a known manner, for example by intimately mixing and/or grinding the active substances with diluents, for example with solvents, solid carriers, and, if desired, surface-active compounds (surfactants).
  • compositions can also contain further additives, such as stabilizers, defoamers, preservatives, viscosity regulators, binders, tackifiers and also fertilizers or other active substances for achieving specific effects.
  • further additives such as stabilizers, defoamers, preservatives, viscosity regulators, binders, tackifiers and also fertilizers or other active substances for achieving specific effects.
  • diluent as used herein means liquid or solid agriculturally acceptable material, which may be added to the active agent to bring it into an easier or better applicable form, resp. to dilute the active agent to a usable or desirable strength of activity.
  • diluents are talc, kaolin, diatomaceous earth, xylene or water.
  • Especially formulations used in spray form may contain surfactants such as wetting and dispersing agents, e.g. the condensation product of formaldehyde with naphthalene sulphonate, an alkylarylsuphonate, a lignin sulphonate, a fatty alkyl sulphate, and ethoxylated alkylphenol and an ethoxylated fatty alcohol.
  • surfactants such as wetting and dispersing agents, e.g. the condensation product of formaldehyde with naphthalene sulphonate, an alkylarylsuphonate, a lignin sulphonate, a fatty alkyl sulphate, and ethoxylated alkylphenol and an ethoxylated fatty alcohol.
  • the formulations include from 1 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and from 10 to 99% diluent(s).
  • Concentrated forms of compositions e.g. emulsion concentrates, contain in general from about 5 to 70%, preferably from between 10 and 50% by weight of active agent.
  • Applications forms of formulations e.g. spray suspensions applied to loci of insects and Acarina, contain in general from 1 ppm to 5000 ppm of a compound of the invention as active agent.
  • Typical spray-suspensions may, for example, contain from 10 ppm to 1000 ppm of active agent, preferably between 20 and 500 ppm.
  • the application rates per hectare are generally 10 to 1000 g of active substance per hectare, preferably 20 to 500 g/ha.
  • More appropriate application rates can be determined by outline experiments by those skilled in the art, or by comparing the activity of the compound of formula I with standards for which the application rate is known.
  • satisfactory control of insects is obtained when employing the compound of formula I at a rate of from about 20 g active ingredient (a.i.)/ha to 500 g/ha of insect-infested habitat, preferably from about 50 g/ha to 400 g/ha.
  • Satisfactory control of Acarina is obtained when employing the compound of formula I at a rate from about 20 g active ingredient (a.i.)/ha to 100 g/ha of Acarina-infested habitat.
  • Satisfactory control of plant fungi is obtained when employing the compound of formula I at a rate of from about 20 g/ha to 500 g/ha, preferably from about 100 g/ha to 400 g/ha of plant fungus infested habitat.
  • compositions of the invention may comprise further additives with special purposes, e.g. stabilizers, deactivators (for solid formulations or carriers with an active surface), agents for improving the adhesion to plants, corrosion inhibitors, anti-foaming agents and colorants.
  • stabilizers for solid formulations or carriers with an active surface
  • deactivators for solid formulations or carriers with an active surface
  • agents for improving the adhesion to plants e.g. corrosion inhibitors, anti-foaming agents and colorants.
  • Rice plants (Oryza sativa) were sprayed with 1 concentration, 500 mg a.i./liter, using a spray tunnel (1 plant per concentration). After drying of the spray deposit, each plant was infested with 10 nymphs (L2 to L3) of the green rice leafhopper, Nephotettix cincticeps.
  • Potted bushbean plants (Phaseolus vulgaris), infested 2 days before spraying with approximately 20 mites of Tetranychus urticae Tetranychidae, two-spotted spider mites, mixed population of adults, nymphs and larvae) are sprayed using a spray tunnel. 2 concentrations are applied (500 and 100 mg a.i./liter spray dilution). Surviving mites are counted 2 and 8 days after the treatment. Efficacy in % is calculated according to Abbott.
  • Phaedon cochleariae (mustard beetle)
  • Tetranvchus urticae two-spotted spider mite
  • Plants of Cucumis sativus (cucumber), 7 days old (cotyledon stage), are sprayed to near run off with a suspension containing 250 mg/1 of active ingredient. The deposit is then allowed to dry. One day later, the treated plants are inoculated with a spore suspension containing 1 ⁇ 10 5 /ml of freshly collected conidia of Sphaerotheca fuliginea and then incubated in the greenhouse for 7 days at +24°C and 60% r.h.
  • the efficacy of the test compounds is determined by comparing the degree of fungal attack with that on untreated, similarly inoculated check plants.
  • This test compounds 1.02, 1.03, 1.05, 1.07, 1.09, 1.11, 1.12, 1.13, 1.15, 1.16, 1.17, 1.18, 1.20, 1.21, 1.29, 1.31, 2.02, 2.07, 2.10, 2.13, 2.14, 2.19, 3.03, 3.04, 3.09, 3.11, 3.12, 3.15, 4.09, 4.10, 4.13, 4.15, 4.16, 4.17 and 4.18 showed an efficacy of 90% or more.
  • Plants of Phaseolus vulgaris (pole bean), 14 days old (2 leaves stage), are sprayed to near run off with a suspension containing 250 mg/1 of the active ingredient. The deposit is then allowed to dry. One day later, the treated plants are inoculated with a spore suspension containing 1 ⁇ 10 5 /ml of freshly collected spores of Uromyces appendiculatus. Incubation is performed for 3 days in a high humidity cabinet at 23°C and >95% r.h. and thereafter during 10 days at +24°C and 60% r.h.
  • the efficacy the compounds is determined by comparing the degree of fungal attack with that on untreated, similarly inoculated check plants.
  • 1.20, 1.21, 2.02, 2.07, 2.08, 2.09, 2.10, 2.13, 2.14, 2.19, 2.20, 3.03, 3.04, 3.09, 3.1 1, 3.12, 4.09, 4.10, 4.14, 4.15, 4.20, 4.22 and 4.23 showed an efficacy of 90% or more.
  • Plants of Lycopericon esculentum (tomato) with 6 leaves are sprayed to near run off with a spray suspension containing 250 mg/1 of the active ingredient. The deposit is then allowed to dry. 1 day later, the treated plants are inoculated with a spore suspension containing 1 ⁇ 10 5 /ml of freshly collected sporangia of Phytophthora infestans and the incubated for 7 days in a high humidity cabinet at +18°C and >95% r.h.
  • the efficacy of the test compounds is determined by comparing the degree of fungal attack with that on untreated, similarly inoculated check plants. In this test compounds 1.07, 1.11, 1.12, 1.18, 1.29, 1.31, 2.02, 2.07, 2.09, 2.19, 3.15, 3.16, 4.16, 4.18, 4.19, 4.20 and 4.25 showed an efficacy of 90% or more.
  • the compounds of the invention may also be used for seed treatment.
  • the advantageous fungicidal activity is established by in vitro tests with the following pathogens:
  • Autoclaved wheat seeds are inoculated with spores or mycelium of the pathogens and coated with different concentrations of the test compound resulting in dosages of 50g a.i./ 1000kg seed.
  • the treated seeds are then placed on agar plates and the pathogens allowed to grow for 3-8 days at +24°C in the dark.
  • the efficacy of the test compounds is determined by comparing the degree of fungal growth emerging from treatment and untreated inoculated seeds.

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Abstract

The invention discloses 2-[4-(2-(pyrimidin-4-yloxy- and -4-ylamino)-ethyl-phenyl]-dioxolanes of formula (I) wherein R1 is hydrogen, C1-4alkyl, C1-4haloalkyl or C3-6cycloalkyl, R2 is hydrogen, C1-10alkyl, C1-8alkoxy-C1-4alkyl, C3-8alkenyloxy-C1-4alkyl, C3-8haloalkenyloxy-C1-4alkyl, C3-8alkynyloxy-C1-4alkyl, C1-8haloalkoxy-C1-4alkyl, C1-8alkylthio-C1-4alkyl, aryl, aryloxy-C1-4alkyl, aryl-C1-4alkoxy-C1-4-alkyl, heteroaryloxy-C1-4alkyl, C1-4alkoxy-C1-4alkoxy-C1-4alkyl or aryl-C1-8alkyl, R3 and R4 independently are halogen, C1-4alkyl, C1-4alkoxy, C1-4alkoxy-C1-4alkyl, C1-4alkoxycarbonyl-C1-4alkyl, C1-4alkoxycarbonyl, cyano-C1-4alkyl, cyano, or -COOH, or R3 and R4 together form a bridge member selected from 1,4-butylene, 1,4-butadienylene, or -S-CH=CH-, each optionally substituted by one or two radicals selected from halogen or C1-4alkyl, and Z is NH or oxygen; the use of such compounds for the control of undesired acarinae, fungi, and insects, compositions for facilitating such use, and the preparation of the compounds of formula I.

Description

NOVEL PYRIMIDINYLOXY- AND PYRIMIDINYLAMINO-ETHYLPHENYL- DIOXOLANE DERIVATIVES
The present invention relates to novel 2-[4-(2-(2-pyrimidin-4-yloxy-and -4-ylamino)-ethyl)-phenyl]-dioxolanes, the synthesis thereof, and the use of said compounds for controlling undesired acarinae, fungi, and insects.
It has been found that 2-[4-(2-(2-pyrimidin-4-yloxy- and -4-ylamino)-ethyl)-phenyl]-dioxolanes of formula I
Figure imgf000003_0001
wherein
R1 is hydrogen, C1-4alkyl, C1-4haloalkyl or C3-6cycloalkyl,
R2 is hydrogen, C1-10alkyl, C1-8alkoxy-C1_4alkyl, C3.8alkenyloxy-C1-4alkyl,
C3-8haloalkenyloxy-C1-4alkyl, C3.galkynyloxy-C1-4alkyl, C,.8haloalkoxy-C1-4alkyl,
C1-8alkylthio- C1-4alkyl, atyl, aryloxy-C1-4alkyl, aryl-C1-4alkoxy-C1-4alkyl,
heteroaryloxy-C1-4alkyl, C1-4alkoxy-C1-4alkoxy-C1-4alkyl, or aryl-C,.8alkyl,
R3 and R4 independently are halogen, C1-4alkyl, C1-4alkoxy, C1-4alkoxy-C1-4alkyl,
C1-4alkoxycarbonyl-C1-4alkyl, C1-4alkoxycarbonyl, cyano-C1-4alkyl, cyano, or
-COOH, or
R3 and R4 together form a bridge member selected from 1,4-butylene, 1,4-butadienylene, or -S-CH=CH- each optionally substituted by one or two radicals selected form halogen or C1-4alkyl, and
Z is NH or oxygen,
exhibit strong pesticidal activity, especially strong acaricidal, fungicidal, and insecticidal activities. In particular the compounds of formula I are suitable for controlling plant pests of the orders of acarines and of insects. Further, the compounds of formula I provide fungicidal activity against phytopathogenic fungi.
In the definitions of the radicals of formula I alkyl is understood to encompass straight-chain and branched alkyl groups, with straight-chain and lower alkyl being preferred. Examples for alkyl are methyl, ethyl, n-propyl, i-propyl, n-butyl, sec.-butyl, tert. butyl, i-butyl, and the isomeric forms of pentyl, hexyl, heptyl, octyl, nonyl or decyl. Cycloalkyl designates cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Alkoxy for example encompasses methoxy, ethoxy, n-propoxy, i-propoxy, n-butyloxy, sec. butyloxy, tert. butyloxy, i-butyloxy and the isomeric forms of pentyloxy, hexyloxy, heptyloxy, or octyloxy. Halogen designates fluorine, chlorine, bromine and iodine, with fluorine and chlorine being preferred. Alkenyloxy for example designates allyloxy, methallyloxy, 2-butenyloxy, 3-butenyloxy and the isomeric forms of pentenyloxy, hexenyloxy, heptenyloxy, or octenyloxy. Alkynyloxy designates for example propargyloxy,
2-butynyloxy, 3-butynyloxy and the isomeric forms of pentynyloxy, hexynyloxy, heptynyloxy or octynyloxy. Aryl stands for an aromatic hydrocarbon radical, for example phenyl or naphthyl, with phenyl being preferred. Aryloxy designates an aryl radical being bounded through an oxygen atom. Examples are phenoxy, α-naphthyloxy or
β-naphthyloxy. Heteroaryloxy stands for an aromatic 5- to 6-membered cyclic radical comprising one, two or three atoms being selected from nitrogen, oxygen or sulfur, and being bounded through an oxygen atom. The heteroaryl group of heteroaryloxy groups may also be in condensed form with another heteroaryl radical or an aryl radical.
Examples are pyridyl, pyrimidinyl, triazolyl, triazinyl, thienyl, oxazolyl, oxadiazolyl, pyrazolyl, imidazolyl, pyrrolyl, furyl, thiadiazolyl, and the like. Cyanoalkyl designates an alkyl group being substituted with one or two cyano groups, with one cyano group being preferred. Examples are cyanomethyl, 1-cyanoethyl, 2-cyanoethyl and the isomers of cyanopropyl or cyanobutyl. Alkoxycarbonyl designates for example methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butyloxycarbonyl, sec-butyloxycarbonyl, tert. butyloxycarbonyl or i-butyloxycarbonyl. When R3 and R4 together form a bridge member the pyrimidinyl ring forms a part of a condensed bicyclic ring system. Such bicyclic ring systems are for example quinazoline, tetrahydroquinazoline, thieno[2,3-d]pyrimidine or thieno[3,2-d]pyrimidine. Where defined substituents are combined from various definitions, each of the definitions has the meanings given thereunder. For example haloalkyl designates an alkyl group being mono- to perhalogenated. Examples are trifluoromethyl, difluoromethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, chloromethyl, fluoromethyl, and the like.
Alkoxyalkyl for example designates methoxy methyl, ethoxymethyl, propoxymethyl, ethoxyethyl, methoxyethyl, butyloxymethyl, isopropoxymethyl, methoxypropyl, and the like. Alkenyloxyalkyl is for example allyloxymethyl, methallyloxymethyl, allyloxyethyl, methallyloxyethyl, 2-butenyloxymethyl, and the like. Haloalkenyloxyalkyl for example encompasses 2-chloroallyloxymethyl and the like. Alkynyloxyalkyl for example designates propargyloxymethyl or propargyloxyethyl. Haloalkoxyalkyl for example is
2-fluoroethoxymethyl. Alkylthioalkyl encompasses for example methylthiomethyl or ethylthiomethyl. Examples for aryloxyalkyl are 4-chlorophenoxymethyl, phenoxymethyl or 2-methoxyphenoxymethyl. Examples for arylalkoxyalkyl are benzyloxymethyl or methylbenzyloxymethyl. Examples for heteroaryloxyalkyl are pyrazolyloxymethyl or pyrimidinyloxymethyl. Examples for alkoxyalkoxyalkyl are methoxy ethoxymethyl, ethoxyethoxymethyl or propoxy ethoxymethyl. Examples for alkoxycarbonylalkyl are methoxycarbonylmethyl or ethoxycarbonylmethyl. Examples for arylalkyl are benzyl, phenethyl, 1-phenylethyl, phenylpropyl, phenylbutyl or the like.
The compounds of formula I contain one or more asymmetrical carbon atoms. These compounds may therefore exist in optical pure form or in mixtures of the isomeric forms. Where optically pure forms are intended in this document they are mentioned specifically. In all other cases mixtures of the isomeric forms are intended, as e.g. obtained from the applied synthesis method. Where mixtures of isomers are obtained during synthesis, the pure isomers may be obtained from the mixtures by known separation techniques, such as crystallization, chromatography or destination, or by combined derivatisation/separation methods.
Among the compounds of formula I those subgroups are preferred, wherein either a) R3 and R4 together form an optionally substituted 1,4-butylene or butadienylene bridge, thus together with the pyrimidine ring to which they are attached form an optionally substituted tetrahydroquinazoline or quinazoline moiety, or b) R1 is hydrogen or methyl, or c) R2 is C1-8alkyl, C1-8alkoxy-C1-4alkyl, C3-8alkenyloxy-C1-4alkyl, or C1-4alkoxy- C1-4alkoxy-C1-4alkyl.
An even more preferred subgroup of compounds of formula I encompasses those compounds wherein R1 is hydrogen or methyl, R2 is C1-8alkyl, C1-8alkoxy- C1-8alkyl, C3-8alkenyloxy-C1-4alkyl, or C1-4alkoxy-C1-4alkoxy-C1-4alkyl, and R3 and R4 together form an optionally substituted 1 ,4-butylene or butadienylene bridge.
Preferred individual compounds of formula I are:
4-allyloxymethyl-2-methyl-2[4-(2-(quinazolin-4-yloxy)-ethyl)-phenyl]-dioxolane,
4-allyloxymethyl-2-methyl-2-[4-(2-(5,6,7,8-tetrahydroquinazolin-4-yloxy)-ethyl)-phenyl]- dioxolane, 4-butyl-2-methyl-2-[4-(2-(quinazolin-4-yloxy)-ethyl)-phenyl]-dioxolane, and 4- butyl-2-methyl-2-[4-(2-(5-methyl-thieno[2,3-d]pyrimidin-4-ylamino)-ethyl)-phenyl]- dioxolane.
The compounds of formula I wherein Z is oxygen may be obtained by reacting a 2-[4-(2- hydroxyethyl)-phenyl]-dioxolane of formula II
Figure imgf000006_0001
wherein R1 and R2 are as defined for formula I, with a 4-halopyrimidine of formula III
Figure imgf000006_0002
wherein R3 and R4 are as defined for formula I, and Hal is halogen, preferably chlorine or bromine.
The reaction (II + III→ I) may be carried out in a manner known per se for etherification methods. The etherification is advantageously carried out in the presence of a base. Also, conveniently the reaction is carried out in the presence of an inert solvent. The reaction temperature is in general between 0°C and the boiling temperature of the reaction mixture, preferably is between room temperature and the boiling temperatures of the solvents used. Examples for suitable bases include alkaline metal hydrides such as sodium hydride, and alkaline metal hydroxides such as sodium hydroxide, potassium hydroxide. In the case of alkaline metal hydroxides the ether formation is advantageously carried out in the presence of a phase transfer catalyst such as triethylbenzylammonium chloride or bromide (TEBA), tetrabutyl ammonium chloride, etc. and a suitable inert solvent like aromatic hydrocarbons such as benzene and toluene. When alkaline metal hydrides, such as sodium hydride, are used, examples of suitable inert solvents are hydrocarbons such as toluenes, ethers such as diethyl ether, tetrahydrofuran and 1,2-dimethoxyethane; polar solvents such as
dimethylformamide or acetonitrile; and mixtures comprising two or more of them. The desired end-product is isolated and purified according to known techniques, for example by evaporation of solvent, chromatography or crystallization.
The compounds of formula II may be obtained by hydrolysing a compound of formula IV
Figure imgf000007_0001
wherein R1 and R2 are as defined for formula I and X is hydrogen, C1-4alkyl, C1-4alkoxy, halo, nitro or cyano, and Y is hydrogen, C1-4alkyl, C1-4alkoxy, halo or cyano, in the presence of a base.
The hydrolization reaction (IV→ II) may be carried out in a manner known per se for alkaline hydrolization reactions of carboxylic acid esters. The reaction is preferably carried out in the presence of a base. Advantageously the reaction is carried out in an aqueous solution, or in a mixture of water and an inert organic solvent. Preferred such solvents are miscible with water, such as alcohols, e.g. methanol, ethanol or isopropanol, or are aromatic hydrocarbons such as toluene and xylene in which case, preferably, a phase transfer catalyst is being used. In general all types of inorganic bases may be used.
Examples are sodium or potassium hydroxide. Reaction temperatures are between 0°C and +100°C, preferably between +20°C and +50°C.
The compounds of formula IV may be obtained by acetalising a compound of formula V
Figure imgf000008_0001
wherein R1, X and Y are as defined for formula IV with a glycol of formula VI
Figure imgf000008_0002
wherein R2 is as defined for formula I.
The reaction (V + VI→ FV) corresponds to a standard acetalisation reaction, which may be conducted in the manner known per se for acetalisation reactions. For example the reaction may be catalyzed in the presence of an organic acid or a strong inorganic acid such as cone, sulfuric acid, and the water resulting as one condensation product may be separated continuously from the reaction mixture by azeotropic destination. In a typical procedure the reactants of formula V and VI are solved in an inert solvent, suitable for azeotropic destination, e.g. benzene, toluene, xylene or chloroform, a catalytic amount of toluene sulfonic acid or cone, sulfuric acid is added, and the reaction mixture is heated to reflux while exporting the condensating water via a suitable condenser e.g. a Dean-Stark trap.
In an alternative method the compounds of formula II may also be prepared by acetalising a compound of formula VII
Figure imgf000008_0003
wherein R1, X and Y are as defined for formula IV with a glycol of formula VI
Figure imgf000009_0003
wherein R2 is as defined for formula I.
The acetalisation (VII + VI→ II) may be conducted by a method similar to the described method for obtaining the compounds of formula IV from compounds of formula V and VI.
The compounds of formula V may be obtained by reacting a compound of formula VIII
Figure imgf000009_0002
wherein X and Y are as defined for formula IV with an carboxylic acid derivative of formula X
Figure imgf000009_0001
wherein R'1 is C1-4alkyl, C1-4haloalkyl or C3-6cycloalkyl and L is chlorine or bromine.
The reaction (VIII + IX→ V) corresponds to a standard acid-catalyzed Friedel-Crafts acylation. The reaction is preferably carried out in the presence of a Lewis acid, like aluminium chloride or in the presence of a proton acid such as sulfuric acid. In a typical procedure the reactants of formula VIII + IX are added to a suspension of a stochiometric amount of anhydrous aluminium chloride in a solvent, e.g. dichloromethane chloroform, nitrobenzene or carbon disulfide. The reaction temperature is preferably between 0°C and +30°C.
The compounds of formula I whrein Z is NH may be obtained by reacting a 2-[4-(2-aminoethyl)-phenyl]-dioxolane of formula X
Figure imgf000010_0001
whrein R1 and R2 are as defined as defined for formula I, with a 4-halopyrimidine of formula III
Figure imgf000010_0002
wherein R3 and R4 are as defined for formula I, and Hal is halogen, preferably chlorine or bromine.
The reaction (X + IIl→ I) may be carried out in a manner known per se for the reaction of amines with alkylhalides or heterocyclic halides, e.g. of 2-halopyridines or 2-, or 4-halopyrimidines. The reaction is advantageously carried out in the presence of a base. Preferably the reaction is carried out in an aqueous solution, or in a mixture of water and an inert organic solvent. Preferred are such solvents which are miscible with water, such as alcohols, e.g. methanol, ethanol or isopropanol, or are aromatic hydrocarbons such as toluene and xylene in which case, preferably, a phase transfer catalyst is being used. In general all types of inorganic bases may be used, appropriate are especially sodium hydroxide, potassium hydroxide, sodium carbonate, or potassium carbonate. Reaction temperatures are between 0°C and +100°C, preferably between +50°C and +100°C.
The compounds of formula X may be obtained by hydrolising a compound of formula XI
Figure imgf000010_0003
wherein R1 and R2 are as defined for formula I.
The hydrolization reaction (XI→ X) may be carried out in a manner known per se for the hydrolysis of phthalimide derivatives. The reaction is preferably carried out in the presence of an amine or hydrazine. For instance hydrazine, methylamine, ethylamine, propylamine, 2-propylamine, butylamine or pentylamine may be applied.
Advantageously the reaction is carried out in an aqueous solution, or in an inert organic solvent. Preferred solvents are alcohols, such as methanol, ethanol or isopropanol.
Reaction temperatures are between 0°C and +100°C, preferably between +20°C and +50°C.
The compounds of formula XI may be obtained by converting a compound of formula XII
Figure imgf000011_0001
wherein R1 and R2 are as defined for formula I and Hal is halogen, preferably chlorine or bromine with phthalimide.
The reaction (XII→ XI) may be carried out in a manner known per se for the alkylation of amines. The reaction is advantageously carried out in the presence of a base. Preferably the reaction is carried out in an inert organic solvent.
In an alternative method the compounds of formula XII may be obtained by reacting a compound of formula II
Figure imgf000011_0002
wherein R1 and R2 are as defined for formula I with phthalimide. The reaction (II→ XI) may be carried out in a manner known per se for the Mitsunobu reaction (O. Mitsunobu, Synthesis, 1981. p. 1 ff; and D.L. Hughes, Org. Reaction, 1982, Vol. 42, p. 395 ff). It is adventageously carried out in the presence of an organo-phosphorus compound, e.g. triphenylphosphine, tritolylphosphine or tributylphosphine and an azodicarboxylate, for instance diethyl azodicarboxylate or diisopropyl azodicarboxylate. Preferably the reaction is carried out in an inert organic solvent, e.g. diethyl ether, dioxane or tetrahydrofuran.
The compounds of formula XII may be obtained by acetalising a compound of formula
XIII
Figure imgf000012_0001
wherein R, and Hal are as defined for formula XII with a glycol of formula VI
Figure imgf000012_0002
wherein R2 is as defined for formula I.
The reaction (XIII + VI→ XII) corresponds to standard acetalisation reaction, which may be conducted in the manner known per se for acetalisation reactions. For example the reaction may be catalyzed in the presence of an organic acid or a strong inorganic acid such as cone, sulfuric acid, and the water resulting as one condensation product may be separated continuously from the reaction mixture by azeotropic destination. In a typical procedure the reactants of formula Xm and VI are solved in an inert solvent, suitable for azeotropic destination, e.g. benzene, toluene, xylene or chloroform, a catalytic amount of toluene sulfonic acid or cone, sulfuric acid is added, and the reaction mixture is heated to reflux while exporting the condensating water via a suitable condenser e.g. a Dean-Stark trap. The intermediate compounds of formulae II, IV, V, X, XI and XII are novel, and have especially been developed for the preparation of the active ingredients of formula I.
Therefore, these compounds belong to the same inventive concept and thus constitute a part of the present invention.
The starting materials of formulae III, VI, VII, VIII, IX and XIII are known in the art, or may be prepared according to known methods.
The compounds of formula I are effective against plant-damaging Arthropodae belonging to the order of Acarine, as well as to the class of Insects and against phytopathogenic fungi.
Their advantageous fungicidal activity is established by in vivo tests with test
concentration from 0.5 to 500 mg a.i./l against Uromyces appendiculatus on pole beans, against Puccinia triticina on wheat, against Sphaerotheca fuliginea on cucumber, against Erysiphe graminis on wheat and barley, against Podosphaera leucotricha on apple, against Uncinula necator on grape vine, against Leptosphaeria nodorum on wheat, against
Cochliobolus sativus and Pyrenophora graminea on barley, against Venturia inaequalis on apple, against Phytophthora infestans on tomato and against Plasmopara viticola on grape vine.
Many of the compounds of formula I have an excellent plant tolerance. The compounds of the invention are therefore indicated for treatment of plants, seeds and soil to combat phytopathogenic fungi, e.g. Basidiomycetes of the order Uredinales (rusts) such as
Puccinia spp, Hemileia spp, Uromyces spp; and Ascomycetes of the order Erysiphales (powdery mildew) such as Erysiphe ssp, Podosphaera spp, Uncinula spp, Sphaerotheca spp; as well as Cochliobolus; Pyrenophora spp; Venturia spp; Mycosphaerella spp;
Leptosphaeria; Deuteromycetes such as Pyricularia, Pellicularia (Corticium), Botrytis; and Oomycetes such as Phytophthora spp, Plasmopara spp.
A subgroup of compounds of formula I are particularly effective against powdery mildew and rust, Pyrenophora and Leptosphaeria fungi in particular against pathogens of monocotyledonous plants such as cereals, including wheat and barley . Another subgroup of compounds of formula I are particularly effective against Oomycetes on dicotyledonous plants such as grapevine, tomatoes or potatoes.
It has been found that the compounds of formula I are particularly useful for controlling insects, particularly black bean aphids (Aphis fabae), green rice leafhoppers (Nephotettix cincticeps), mustard beetles (Phaedon cochleariae), and mosquitos (Aedes aegypti). This application therefore provides a method of controlling insects comprising applying to the insects or their locus an insecticidally effective amount of the compounds of formula I.
It has further been found that the compounds of formula I are particularly useful for controlling Acarina, especially the two-spotted spider mite (Tetranychus urticae) and the European red mite (Panonychus ulmi). This application therefore provides a method of controlling Acarina comprising applying to the Acarina or their locus an acaricidally effective amount of the compounds of formula I.
The compounds of the formula I are employed in unaltered form, i.e., as a pure substance as obtained from the synthesis, dried and ground, or preferably together with the auxiliaries conventionally used in the art of formulation, and they can therefore be processed in a known manner for example to emulsion concentrates, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granules and also encapsulations in polymeric substances. The application methods, such as spraying, misting, atomizing, scattering or pouring, as well as the compositions, are selected to suit the intended aims and the prevailing circumstances.
The compounds of the invention may be used in a great number of crops, such as soybean, coffee, ornamentals (i.a. pelargonium, roses) vegetables (e.g. peas, cucumber, celery, tomato and bean plants), sugarbeet, sugarcane, cotton flax, maize (com), vineyards, pomes and stone fruits (e.g. apple, pears, prunes) and in cereals (e.g. wheat, oats, barley, rice).
The invention also provides acaricidal, fungicidal and insecticidal compositions, comprising as active ingredient a compound of formula I in association with an agriculturally acceptable diluent (hereinafter diluent). They are obtained in conventional manner, e.g. by mixing a compound of the invention with a diluent and optionally additional ingredients, such as surfactants.
The formulations, i.e. the compositions, preparations or combinations, containing the active substance of the formula I or combinations of this active substance with other fungicides, insecticides or acaricides, and if desired a solid or liquid additive, are prepared in a known manner, for example by intimately mixing and/or grinding the active substances with diluents, for example with solvents, solid carriers, and, if desired, surface-active compounds (surfactants).
The compositions can also contain further additives, such as stabilizers, defoamers, preservatives, viscosity regulators, binders, tackifiers and also fertilizers or other active substances for achieving specific effects.
The term diluent as used herein means liquid or solid agriculturally acceptable material, which may be added to the active agent to bring it into an easier or better applicable form, resp. to dilute the active agent to a usable or desirable strength of activity. Examples of such diluents are talc, kaolin, diatomaceous earth, xylene or water.
Especially formulations used in spray form, such as water dispersible concentrates or wettable powders, may contain surfactants such as wetting and dispersing agents, e.g. the condensation product of formaldehyde with naphthalene sulphonate, an alkylarylsuphonate, a lignin sulphonate, a fatty alkyl sulphate, and ethoxylated alkylphenol and an ethoxylated fatty alcohol.
In general, the formulations include from 1 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and from 10 to 99% diluent(s). Concentrated forms of compositions, e.g. emulsion concentrates, contain in general from about 5 to 70%, preferably from between 10 and 50% by weight of active agent. Applications forms of formulations, e.g. spray suspensions applied to loci of insects and Acarina, contain in general from 1 ppm to 5000 ppm of a compound of the invention as active agent. Typical spray-suspensions may, for example, contain from 10 ppm to 1000 ppm of active agent, preferably between 20 and 500 ppm. The application rates per hectare are generally 10 to 1000 g of active substance per hectare, preferably 20 to 500 g/ha.
More appropriate application rates can be determined by outline experiments by those skilled in the art, or by comparing the activity of the compound of formula I with standards for which the application rate is known. In general, satisfactory control of insects is obtained when employing the compound of formula I at a rate of from about 20 g active ingredient (a.i.)/ha to 500 g/ha of insect-infested habitat, preferably from about 50 g/ha to 400 g/ha. Satisfactory control of Acarina is obtained when employing the compound of formula I at a rate from about 20 g active ingredient (a.i.)/ha to 100 g/ha of Acarina-infested habitat. Satisfactory control of plant fungi is obtained when employing the compound of formula I at a rate of from about 20 g/ha to 500 g/ha, preferably from about 100 g/ha to 400 g/ha of plant fungus infested habitat.
In addition to the usual diluents and surfactants, the compositions of the invention may comprise further additives with special purposes, e.g. stabilizers, deactivators (for solid formulations or carriers with an active surface), agents for improving the adhesion to plants, corrosion inhibitors, anti-foaming agents and colorants.
Examples of plant acaricide, fungicide and insecticide formulations are as follows: a. Wettable Powder Formulation
10 Parts of a compound of formula I are mixed and milled with 4 parts of synthetic fine silica, 3 parts of sodium lauryl sulphate, 7 parts of sodium lignin sulphonate and 66 parts of finely divided kaolin and 10 parts of diatomaceous earth until the mean particle size is about 5 micron. The resulting wettable powder is diluted with water before use to a spray liquor which may be applied by foliar spray as well as by root drench application. b. Granules
Onto 94.5 parts by weight of quartz sand in a tumbler mixer are sprayed 0.5 parts by weight of a binder (non-ionic tensile) and the whole thoroughly mixed. 5 parts by weight of a compound of formula I of this invention are then added and thorough mixing continued to obtain a granulate formulation with a particle size in the range of from 0.3 to 0.7 mm (where required, the granules may be dried by the addition of 1 to 5 % by weight of talcum). The granules may be applied by incorporation into the soil adjacent to the plants to be treated. c. Emulsion Concentrate
10 Parts by weight of a compound of formula I are mixed with 10 parts by weight of an emulsifier and 80 parts by weight of xylene. The thus obtained concentrate is diluted with water to form an emulsion of the desired concentration, prior to application.
The following examples further illustrate the present invention. They do not restrict the present invention. All temperatures are in centigrade. Rf values are obtained by thin layer chromatography on silica gel, unless otherwise specified.
Example 1 : 4-Allyoxymethyl-2-methyl-2-[4-(2-(quinazolin-4-yloxy)-ethyl-phenul]- dioxplane
Figure imgf000017_0001
a) 4-acetylphenylethyl benzoate
Figure imgf000017_0002
263 g (2.0 mole) of anhydrous aluminium chloride are suspended in 1800 ml
dichloromethane. After the mixture is cooled to 0°C, 81 g (1.0 mole) of acetyl chloride and 212 g (0.8 mole) of phenylethyl benzoate are added one after the other. Subsequently the reaction is stirred for 16 hours at room temperature and then poured into a mixture of 500 ml crushed ice and 900 ml cone, hydrochloric acid. After separation of the phases, the aqueous layer is extracted with 2 x 400 ml dichloromethane. The combined organic layer is washed with water and 10% aqueous potassium hydrocarbonate solution, dried over magnesium sulfate and evaporated in vacuum. The residue is recrystallized from an ethylacetate/hexane mixture. Yield: 165 g of 4-acetylphenylethyl benzoate,
m.p. 90.5 - 91.5°C.
b) 2-[4-(4-allyloxymethyl-2-methyl-dioxolan-2-yl)-phenyl]-ethyl benzoate
Figure imgf000018_0001
203 g (0.75 mole) of 4-acetylphenylethyl benzoate are dissolved in 1000 ml toluene. To this solution 150 g (1.1 mole) of glycerol-1-allylether and 2.5 g of 4-toluene sulfonic acid are added. The resulting mixture is heated at reflux for 4 hours using a Dean-Stark trap, then cooled and poured on 500 ml crushed ice. After separation of the phases, the aqueous layer is extracted with 2 x 300 ml diethyl ether. The combined organic layer is washed with 400 ml of a 10% aqueous potassium bicarbonate solution, dried over magnesium sulfate and evaporated in vacuum.
Yield: 272 g of 2-[4-(4-allyloxymethyl-2-methyl-dioxolan-2-yl)-phenyl]-ethyl benzoate. c) 2[-4-(4-allyloxymethyl-2-methyl-dioxolan-2-yl)-phenyl]-ethanol
Figure imgf000018_0002
5.0 g (13 mmole) 2-[4-(4-allyloxymethyl-2-methyl-dioxolan-2-yl)-phenyl]-ethyl benzoate are stirred in 100 ml of a 10% potassium hydroxide solution in 80% aqueous methanol for 2 hours at room temperature. The mixture is evaporated to the half of the volume, diluted with 100 ml water and extracted with 3 x 100 ml diethyl ether. The combined organic layer is washed with 100 ml water, dried over magnesium sulfate and evaporated in vacuum. The residue is chromatographed on silica gel (hexane/ethyl acetate, 7 : 3).
Yield: 2.4 g of 2-[4-(4-allyloxymethyl-2-methyl-dioxolane-2-yl)-phenyl]-ethanol. d) 0.3 g (12 mmole) of sodium hydride are suspended in 20 ml of 1,2-dimethoxyethane. After the mixture has been cooled to 0°C, a solution of 3.3 g (12 mmole) of
2-[4-(4-allyloxymethyl-2-methyl-dioxolan-2-yl)-phenyl]-ethanol in 10 ml
1 ,2-dimethoxyethane is added dropwise. The reaction is stirred for 1 hour at room temperature and cooled again to 0°C. 2.3 g (14 mmole) 4-chloroquinazoline are added in portions. The reaction mixture is stirred for 3 hours at room temperature, then cooled to 0°C and added dropwise. Subsequently the mixture is extracted with ethyl acetate. The organic layer is dried over magnesium sulfate and evaporated in vacuum. The residue is chromatographed on silica gel (hexane/ethyl acetate, 7:3).
Yield: 3.5 g of 4-allyoxymethyl-2-methyl-2-[4-(2-(quinazolin-4-yloxy)-ethyl)-phenyl]-dioxolane. or
e) To a solution of 202.5g of 2-[4-(4-allyloxymethyl-2-methyl-dioxolan-2-yl)-phenyl]-ethanol in 1200 ml toluene are added successively 600 ml of a 30% aqueous sodium hydroxide solution, 1 1.4g of TEBA (triethylbenzyl ammonium chloride) and 131.6g of 4-chloroquinazoline in portions. The mixture is stirred for 5 hours at room temperature, then extracted with diethylether, and washed with water and brine. The organic layer is dried over magnesium sulfate and evaporated in vacuum. The residue is chromatographed on silica gel with hexane/diethylether 8:2 to 1 :1. Yield: 215g of
4-allyloxymethyl-2-methyl-2-[4-(2-(quinazolin-4-yloxy)-ethyl)-phenyl]-dioxolane, m.p. 62 - 64°C. Example 2: 4-Formylphenylethyl benzoate
Figure imgf000020_0001
To a stirred solution of phenylethyl benzoate (45.2 g , 0.2 mole) in dichloromethane (140 ml) is added at 0°C titanium tetrachloride (114 g, 0.6 mole), followed by 1,1-dichlorodimethyl ether (25.3 g, 0.22 mole). After removal of the cooling bath, a strong evolution of HCl-gas takes place during warm up to room temperature. The reaction mixture is stirred over night at room temperature. The brown mixture is then slowly poured into crushed ice, extracted with dichloromethane, and the extracts are washed with water, saturated potassium bicarbonate solution and brine. The combined organic layer is dried over magnesium sulfate and the solvent removed in vacuum. Column
chromatography on silica gel (eluant: hexane/ethyl acetate, 9: 1 ) first yields some starting material, and later 25.3 g of pure 4-formylphenylethyl benzoate, m.p. 54-56°C.
Example 3 4-Butyl-2-methyl-2-[4-(2-(5-chloro-6-ethylpyrimidin-5-ylamino)-ethyl)- phenyl]-dioxolane
Figure imgf000020_0002
a) N-[4-(4-butyl-2-methyl-dioxolan-2-yl)-phenylethyl]-phthalimide
Figure imgf000020_0003
To a solution of 9.5 g (36 mmol) 2-[4-(4-butyl-2-methyl-dioxolan-2-yl)- phenyl]-ethanol, 10 g (38 mmol) triphenylphosphine and 5.8 g (40 mmol) phthalimide in 400 ml tetrahydrofuran is added dropwise 7.3 g (42 mmole) diethyl azodicarboxylate. The reaction is stirred for 1 hour at room temperature. The solvent is removed in vacuum and the residue is taken up in a ether/hexane mixture. The resulting precipitate is washed with an ether/hexane mixture. The combined filtrate is evaporated in vacuum and the residue is chromatographed on silica gel (hexane/ethyl) acetate 7:3). Yield : N-[4-(4-butyl-2-methyl-dioxolan-2-yl)-phenyl)-phenylethyl]-phthalimide. b) 2-[4-(4-butyl-2-methyl-dioxolan-2-yl)-phenyl]-ethylamine
Figure imgf000021_0001
4.0 g (10 mmol) N-[4-(4-butyl-2-methyl-dioxolan-2-yl)-phenylethyl]- phthalimide are suspended in 40 ml ethanol. 40 ml of a methylamine solution (33% in ethanol) are added slowly. The reaction mixture is stirred for 3 hours at room temperature. Subsequently the mixture is evaporated in vacuum. The residue is sufficiently pure to be used directly in the next step. Yield : 2-[4-(4- butyl-2-methyl-dioxolan-2-yl)-phenyl]-ethylamine. c) A mixture of 2.1 g (7.8 mmol) 2-[4-(4-butyl-2-methyl-dioxolan-2-yl)-phenyl]- ethylamine 1.8 g (10 mmol) 4,5-dichloro-6-ethylpyrimidine and 2.4 g
(23 mmol) sodium carbonate in 40 ml water is heated to reflux for 3 hours, then diluted with water and extracted with 3 x 60 ml ethyl acetate. The combined organic layer is washed with water, dried over magnesium sulfate and evaporated in vacuum. The residue is chromatographed on silica gel (hexane / ethyl acetate 1:1 ). Yield : 4-butyl-2-methyl-2-[4-(2-(5-chloro-6- ethylpyrimidin-4-ylamino)-ethyl-phenyl]-dioxolane.
The compounds of the following tables are obtained in analogous manner. In the tables Ph designates phenyl.
Figure imgf000022_0001
Figure imgf000023_0001
Figure imgf000024_0001
Figure imgf000025_0001
Figure imgf000025_0002
Figure imgf000026_0001
Figure imgf000027_0001
Figure imgf000028_0001
Figure imgf000029_0001
Figure imgf000030_0001
Figure imgf000031_0001
Figure imgf000032_0001
Figure imgf000033_0001
Figure imgf000034_0001
Figure imgf000035_0001
Figure imgf000036_0001
Figure imgf000037_0001
Figure imgf000038_0001
Biological Assay's
In the following tests formulations of compounds of formula I according to Examples a, b or c have been employed in diluted form.
Insecticidal and Acaricidal Tests
Contact and Stomach Action
a) Aphis fabae fhlack bean aohids
2 days before treatment, potted broad bean plants ( Vicia faba), were infested with adults and nymphs of the black bean aphid, Aphis fabae. The plants, which had approx. 30 insects each, were sprayed with 2 concentrations, 500 and 100 mg a.i./liter, using a spray tunnel (1 plant per concentration). 2 days after treatment, the efficacy was measured by comparing the honeydew production with that of the untreated check. 8 days after treatment, a visual estimate of the number of surviving insects was used to calculate the efficacy in %, according to Abbott.
In this test compounds 1.01, 1.03, 1.05, 1.06, 1.08, 1.09, 1.14, 1.22, 1.23, 1.30, 1.31, 3.15, 3.16, 3.09, 4.01, 4.12, 4.13, 4.16, 4.17, 4.18, 4.18, 4.19, 4.20 and 4.25 showed an efficacy of 90% or more at 500 mg/liter. b) Nephtottix cincticeps (green rice leafhopper)
Rice plants (Oryza sativa) were sprayed with 1 concentration, 500 mg a.i./liter, using a spray tunnel (1 plant per concentration). After drying of the spray deposit, each plant was infested with 10 nymphs (L2 to L3) of the green rice leafhopper, Nephotettix cincticeps.
2 days and 5 days after treatment, the number of dead and alive nymphs were counted.
Mortality in %, corrected according to Abbott, was calculated.
In this test compounds 1.05, 1.07, 1.13, 1.15, 1.31, 3.02, 3.03, 3.1 1, 3.12, 3.15, 4.12, 4.13,
4.16, 4.17 and 4.18 showed an efficacy of 90% or more at 500 mg/liter. c) Tetranychus urticae (two-spotted spider mite)
Potted bushbean plants (Phaseolus vulgaris), infested 2 days before spraying with approximately 20 mites of Tetranychus urticae Tetranychidae, two-spotted spider mites, mixed population of adults, nymphs and larvae) are sprayed using a spray tunnel. 2 concentrations are applied (500 and 100 mg a.i./liter spray dilution). Surviving mites are counted 2 and 8 days after the treatment. Efficacy in % is calculated according to Abbott. In this test compounds 1.01, 1.02, 1.03, 1.04, 1.05, 1.06, 1.07, 1.09, 1.10, 1.11, 1.12, 1.21, 1.23, 1.29, 1.30, 1.31, 2.01, 2.02, 2.03, 2.06, 2.10, 2.12, 2.14, 2.18, 2.19, 3.03, 3.04, 3.1 1, 3.12, 3.15, 3.16, 4.01, 4.02, 4.03, 4.05, 4.06, 4.11, 4.14, 4.16, 4.17, 4.18, 4.19, 4.20, 4.21, 4.22, 4.23, 4.24 and 4.25 showed an efficacy of 90% or more at 500 mg/liter after 8 days. Residual Contact Action
Phaedon cochleariae (mustard beetle)
10 adult insects of Phaedon cochleariae (Coleoptera, Chrysomelidae, mustard beetle) are confined in plastic Petri dishes (9 cm/diameter) previously sprayed in a spray tunnel.
2 concentrations are applied (500 and 100 mg a.iTliter spray dilution). Mortality in %
(with Abbott correction) is determined 2 days after the treatment.
In this test compounds 1.13, 1.20 and 3.02 showed an efficacy of 90% or more at
500 mg/liter.
Ovicidal Action
Tetranvchus urticae (two-spotted spider mite)
5 to 7 adult females of Tetranychus urticae are confined in a glue ring of 2 cm diameter on the upper side of bush bean leaves (Phaseolus vulgaris) and allowed to lay eggs during
24 hours. The plants with the eggs are then sprayed after removal of the females, using a spray tunnel. 1 concentration is applied (100 mg a.i./liter spray dilution). Mortality in %
(with Abbott correction), i.e. % corrected unhatched eggs, is calculated 5 days after the treatment.
In this test compounds 1.03, 1.04, 1.05, 1.06, 1.07, 1.09, 1.10, 1.11, 1.13, 1.14, 1.15, 1.17,
1.30, 1.31, 2.01, 2.02, 2.04, 2.06, 2.10, 2.14, 2.18, 3.01, 3.02, 3.03, 3.04, 3.06, 3.09, 3.11,
3.15, 4.02, 4.03, 4.04, 4.06, 4.07, 4.11, 4.13, 4.17, 4.18 and 4.19 showed an efficacy of
90% or more.
Fungjcidal Tests
a) Activity against Powdery Mildew
Sphaerotheca fuliginea:
Plants of Cucumis sativus (cucumber), 7 days old (cotyledon stage), are sprayed to near run off with a suspension containing 250 mg/1 of active ingredient. The deposit is then allowed to dry. One day later, the treated plants are inoculated with a spore suspension containing 1×105/ml of freshly collected conidia of Sphaerotheca fuliginea and then incubated in the greenhouse for 7 days at +24°C and 60% r.h.
The efficacy of the test compounds is determined by comparing the degree of fungal attack with that on untreated, similarly inoculated check plants. In this test compounds 1.02, 1.03, 1.05, 1.07, 1.09, 1.11, 1.12, 1.13, 1.15, 1.16, 1.17, 1.18, 1.20, 1.21, 1.29, 1.31, 2.02, 2.07, 2.10, 2.13, 2.14, 2.19, 3.03, 3.04, 3.09, 3.11, 3.12, 3.15, 4.09, 4.10, 4.13, 4.15, 4.16, 4.17 and 4.18 showed an efficacy of 90% or more.
Similar methods are used to test the compounds against the following pathogens:
Podospaera leucotricha on apple,
Erysiphe grminis on wheat and barley (dry inoculation),
Uncinula necator on grape.
b) Activity against Rush, Scab, Pyrenophora, Leptosphaeria
Uromyces appendiculatus:
Plants of Phaseolus vulgaris (pole bean), 14 days old (2 leaves stage), are sprayed to near run off with a suspension containing 250 mg/1 of the active ingredient. The deposit is then allowed to dry. One day later, the treated plants are inoculated with a spore suspension containing 1×105/ml of freshly collected spores of Uromyces appendiculatus. Incubation is performed for 3 days in a high humidity cabinet at 23°C and >95% r.h. and thereafter during 10 days at +24°C and 60% r.h.
The efficacy the compounds is determined by comparing the degree of fungal attack with that on untreated, similarly inoculated check plants. In this test compounds 1.20, 1.21, 2.02, 2.07, 2.08, 2.09, 2.10, 2.13, 2.14, 2.19, 2.20, 3.03, 3.04, 3.09, 3.1 1, 3.12, 4.09, 4.10, 4.14, 4.15, 4.20, 4.22 and 4.23 showed an efficacy of 90% or more.
Similar methods are used to test the compounds against the following pathogens:
Puccinia triticina on wheat (plants 10 days old),
Pyrnophora graminea on barley,
Leptosphaeria nodorum on wheat,
Venturia inaequalis on apple (plants 21 days old; the spore suspension contains 1 % malt). c) Activity against Downy Mildew
Plants of Lycopericon esculentum (tomato) with 6 leaves, are sprayed to near run off with a spray suspension containing 250 mg/1 of the active ingredient. The deposit is then allowed to dry. 1 day later, the treated plants are inoculated with a spore suspension containing 1×105/ml of freshly collected sporangia of Phytophthora infestans and the incubated for 7 days in a high humidity cabinet at +18°C and >95% r.h. The efficacy of the test compounds is determined by comparing the degree of fungal attack with that on untreated, similarly inoculated check plants. In this test compounds 1.07, 1.11, 1.12, 1.18, 1.29, 1.31, 2.02, 2.07, 2.09, 2.19, 3.15, 3.16, 4.16, 4.18, 4.19, 4.20 and 4.25 showed an efficacy of 90% or more.
A similar method is used to test the compounds against Plasmopara viticola on grape vine.
d) Activity after Seed Treatment
The compounds of the invention may also be used for seed treatment. The advantageous fungicidal activity is established by in vitro tests with the following pathogens:
Pyrenophora graminea,
Ustilago nuda,
Gerlachia nivalis,
Leptoshpaeria nodorum.
Autoclaved wheat seeds are inoculated with spores or mycelium of the pathogens and coated with different concentrations of the test compound resulting in dosages of 50g a.i./ 1000kg seed. The treated seeds are then placed on agar plates and the pathogens allowed to grow for 3-8 days at +24°C in the dark.
The efficacy of the test compounds is determined by comparing the degree of fungal growth emerging from treatment and untreated inoculated seeds.
To evaluate the crop plant tolerance of the compounds, healthy seeds of wheat and barley are coated with the dosages mentioned above. The seeds are then allowed to germinate in petri dishes on moist filter paper in high humidity at +18°C for 10 days. Plant damage is recorded, comparing the growth of treated and untreated seedling.

Claims

Claims:
1. A 2-[4-(2-(pyrimidin-4-yloxy- or -4-ylamino)-ethyl)-phenyl]-dioxolane of formula I
Figure imgf000043_0001
wherein
R1 is hydrogen, C1-4alkyl, C1-4haloalkyl or C3-6cycloalkyl,
R2 is hydrogen, C1-10alkyl, C1-8alkoxy-C1-4alkyl, C3-8alkenyloxy-C1-4alkyl,
C3-8haloalkenyloxy-C1-4alkyl, C3-8alkynyloxy-C1-4alkyl, C1-8haloalkoxy-C1-4alkyl,
C1-8alkylthio-C1-4alkyl, aryl, aryloxy-C1-4alkyl, aryl-C1-4alkoxy-C1-4alkyl, heteroaryloxy- C1-4alkyl, C1-4alkoxy-C1-4alkoxy-C1-4alkyl, or aryl-C1-8alkyl,
R3 and R4 independently are halogen, C1-4 alkyl, C1-4alkoxy, C1-4alkoxy-C1-4alkyl, C1-4alkoxycarbonyl-C1-4alkyl, C1-4alkoxycarbonyl, cyano-C1-4alkyl, cyano, or -COOH, or
R3 and R4 together form a bridge member selected from 1,4-butylene,
1,4-butadienylene, or -S-CH=CH-, each optionally substituted by one or two radicals selected from halogen or C1-4alkyl, and
Z is NH or oxygen.
A compound according to claim 1 wherein R3 and R4 together form an optionally substituted 1 ,4-butylene or butadienylene bridge, thus together with the pyrimidine ring to which they are attached form an optionally substituted tetrahydroquinazoline or quinazoline moiety.
3. A compound according to any one of claims 1 or 2 wherein R1 is hydrogen or methyl.
4. A compound according to any one of claims 1 to 3 wherein R2 is C1-8alkyl, C1-8alkoxy- C1-4alkyl, C3-8alkenyloxy-C1-4alkyl, or C1-4alkoxy-C1-4alkoxy-C1-4alkyl,
5. A compound selected from the group comprising
4-allyloxymethyl-2-methyl-2-[4-(2-(quinazolin-4-yloxy)-ethyl)-phenyl]-dioxolane, 4-allyloxymethyl-2-methyl-2-[4-(2-(5,6,7,8-tetrahydroquinazolin-4-yloxy)-ethyl)- phenyl]-dioxolane, and 4-butyl-2-methyl-2-[4-(2-(quinazolin-4-yloxy)-ethyl)-phenyl]- dioxolane, and 4-butyl-2-methyl-2-[4-(2-(5-methyl-thieno[2,3-d]pyrimidin-4-ylamino)- ethyl)-phenyl]-dioxolane.
6. Process for the preparation of a compound of formula I according to claim 1, which comprises either reacting a 2-[4-(2-hydroxyethyl)-phenyl]-dioxolane of formula II
Figure imgf000044_0001
or a 2-[4-(2-aminoethyl)-phenyl]-dioxolane of formula X
Figure imgf000044_0002
wherein R1 and R2 are as defined for formula I in claim 1, with a 4-halopyrimidine of formula III
Figure imgf000045_0001
wherein R3 and R4 are as defined for formula I in claim 1 and Hal is halogen, preferably chlorine or bromine.
7. Agricultural composition comprising a compound of formula I according to claim 1 and an agriculturally acceptable diluent.
8. Method of combatting acarinae and insects comprising applying to the acarinae and insects or their habitat an acaricidally or insecticidally effective amount of a compound of formula I according to claim 1.
9. Method of combatting phytopathogenic fungi comprising applying to the fungi or their habitat a fungicidally effective amount of a compound of formula I according to claim 1.
10. A 2-[4-(2-hydroxyethyl)-phenyl]-dioxolane of formula II
Figure imgf000045_0002
wherein R1 and R2 are as defined for formula I in claim 1.
11. A process for the preparation of a 2-[4-(2-hydroxyethyl)-phenyl]-dioxolane of formula II according to claim 10 which comprises hydrolysing a compound of formula IV
Figure imgf000046_0002
wherein R1 and R2 are as defined for formula I in claim 1 and X is hydrogen, C1-4alkyl, C1-4alkoxy, halo, nitro or cyano, and Y is hydrogen, C1-4alkyl, C1-4alkoxy, halo or cyano, in the presence of an acid or a base.
12. A compound of formula IV
Figure imgf000046_0001
wherein R1 and R2 are as defined for formula I in claim 1 and X is hydrogen, C1-4alkyl, C1-4alkoxy, halo, nitro or cyano, and Y is hydrogen, C1-4alkyl, C1-4alkoxy, halo or cyano.
13. A process for the preparation of a compound of formula IV according to claim 12 which comprises acetalising a compound of formula V
Figure imgf000047_0001
wherein R1, X and Y are as defined for formula IV in claim 12 with a glycol of formula VI
Figure imgf000047_0002
wherein R2 is as defined for formula I in claim 1.
14. A compound of formula V
Figure imgf000047_0003
wherein R1, X and Y are as defined for formula IV in claim 5.
15. A process for the preparation of a 2-[4-(2-hydroxyethyl)-phenyl]-dioxolane of formula II according to claim 10 which comprises acetalising a compound of formula VII
Figure imgf000047_0004
wherein R1, X and Y are as defined for formula IV in claim 12 with a glycol of formula VI
Figure imgf000048_0001
wherein R2 is as defined for formula I in claim 1.
16. A compound of formula X
Figure imgf000048_0002
wherein R1 and R2 are as defined for formula I in claim 1.
17. A process for the preparation of a compound of formula X according to 16, which comprises hydrolising a compound of formula XI
Figure imgf000048_0003
wherein R1 and R2 are as defined for formula I.
18. A compound of formula XI
Figure imgf000048_0004
wherein R1 and R2 are as defined for formula I in claim 1.
19. A process for the preparation of a compound of formula XI according to claim 18, which comprises reacting a compound of formula II
Figure imgf000049_0001
wherein R1 and R2 are as defined for formule I in claim 1 with phthalimide.
20. A compound of formula XII
Figure imgf000049_0002
wherein R1 and R2 are as defined for formula I in claim 1 and Hal is halogen, preferably chlorine or bromine.
21. A process for the preparation of a compound of formula XII according to claim 20, which comprises acetalising a compound of formula XIII
Figure imgf000049_0003
wherein R1 and Hal are as defined for formula XII in claim 20 with a glycol of formula VI
Figure imgf000049_0004
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US7601725B2 (en) 2004-07-16 2009-10-13 Sunesis Pharmaceuticals, Inc. Thienopyrimidines useful as Aurora kinase inhibitors
WO2006047397A1 (en) * 2004-10-21 2006-05-04 Dow Agrosciences Llc Thieno-pyrimidine compounds having fungicidal activity
WO2007046809A1 (en) * 2005-10-21 2007-04-26 Dow Agrosciences Llc Thieno-pyrimidine compounds having fungicidal activity
US9750252B2 (en) 2012-02-01 2017-09-05 Nihon Nohyaku., Ltd. Arylalkyloxy pyrimidine derivative, pesticide for agricultural and horticultural use containing arylalkyloxy pyrimidine derivative as active ingredient, and use of same

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BR9509877A (en) 1997-09-30
CN1168671A (en) 1997-12-24
CA2206306A1 (en) 1996-06-13
AU4260296A (en) 1996-06-26
WO1996017843A3 (en) 1996-08-22
GB9424676D0 (en) 1995-02-01
JPH10512236A (en) 1998-11-24
EP0796259A2 (en) 1997-09-24
MX9703363A (en) 1998-02-28

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