CA2206306A1 - Novel pyrimidinyloxy- and pyrimidinylamino-ethylphenyl-dioxolane derivatives - Google Patents

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

CA 02206306 1997-0~-28 W O 96/17843 PCTAEPg5/04795 NOVEL PYRIMIDINYLOXY- AND PyR~MTnINyLAMINo~ yLpHENyL~
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 ~r,~rin~e, fungi, and insects.

It has been found that 2-[4-(2-(2-pyriinidin-4-yloxy- and -4-ylamino)-ethyl)-phenyl]-dioxolanes of formula I

R2 Rl R3 R4 \[ ~CH2--CH2--Z~N (~

Wllclcill R, is hydrogen, Cl 4alkyl, C, 1haloalkyl or C3 6cycloalkyl, R2 is hydrogen, C, ,Oalkyl, C, 8alkoxy-C, 4alkyl, C3 8alkenyloxy-C, 4alkyl, C3 8haloalkenyloxy-C, 4alkyl, C3 8alkynyloxy-C, 4alkyl, C, 8haloalkoxy-C, 4alkyl, C, 8alkylthio-C, 4alkyl, aryl, aryloxy-C, 4alkyl, aryl-C,4alkoxy-C, 4alkyl, heteroaryloxy-C, 4alkyl, C, 4alkoxy-C, 4alkoxy-C, 4alkyl, or aryl-C~ 8alkyl, R3 and R4 independently are halogen, C, ~alkyl, C, 4alkoxy, C, 4alkoxy-C, 4alkyl, C, 4alkoxycarbonyl-C, ~alkyl, C, 4alkoxycarbonyl, cyano-C, ~alkyl, cyano, or -COOH, or R3 and R4 together forrn 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 C, 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 CA 02206306 1997-0~-28 Wo 96117843 PCTIEPg5/04795 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 p~cf~ ;d.
F.~rnrles 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 ~le~ign~te$ cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Alkoxy for example enco",p~es 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 11.q.sign~t~s fluorine, chlorine, bromine and iodine, with fluorine and chlorine being lJlt;felled. Alkenyloxy for example rieSign~tes allyloxy, methallyloxy, 2-butenyloxy, 3-butenyloxy and the isomeric forms of pentenyloxy, hexenyloxy, heptenyloxy, or octenyloxy. Alkynyloxy rlesign~te~ for example plu~ yloxy, 2-butynyloxy, 3-butynyloxy and the isomeric forms of penly~lyloxy, hexynyloxy, heptynyloxy or octynyloxy. Aryl stands for an aromatic hydrocarbon radical, for example phenyl or naphthyl, with phenyl being pl~r~ d. Aryloxy ~lesign~t~s an aryl radical being bounded through an oxygen atom. Examples are phenoxy, oc-naphthyloxy or ~-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 helelualyl 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, thi~ olyl, and the like. Cyanoalkyl ~lesign~t~s an alkyl group being substituted with one or two cyano groups, with one cyano group being plere-l~d. 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.

CA 02206306 1997-0~-28 W O96/17843 PCT~EP9S/0479S -3-Where defined substituents are combined from various definitions, each of the definitions has the mP~ning~ given thereunder. For example haloalkyl ~e~ign~tes an alkyl group being mono- to perhalogçn~te~ Examples are trifluololllGlllyL difluoromethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pe"~ olo~ .yl, chlolulllGlllyl7 fluololllGlllyl~ and the like.
Alkoxyalkyl for example design~tP,s methoxymethyl, ethoxyllltlllyl, plopo~ymethyl, ethoxyethyl, methoxyethyl, butylo~LylllGthyl, isopropo,~yllltlhyl, methoxypropyl, and the like. Alkenyloxyalkyl is for example allyloxymethyl, methallyloxymethyl, allyloxyethyl, methallyloxyethyl, 2-butenylo~ylllclhyl, and the like. Haloalkenyloxyalkyl for example encomp~ses 2-chloroallylo~LylllGIhyl and the like. Alkynyloxyalkyl for example designates propargyloxymethyl or pl~pal~yloxyethyl. Haloalkoxyalkyl for example is 2-fluoroethoxymethyl. Alkylthioalkyl enco"-l~a~es for example mt~lylll-iomethyl or ethylthiomethyl. Examples for aryloxyalkyl are 4-chloropheno~yl~,GIhyL phenoxymethyl or 2-methoxyphenoxymethyl. Examples for arylalkoxyalkyl are benzylo~lllelllyl or methylbenzyloxymethyl. Examples for hGIGloalyloxyalkyl are pyrazolyloxymethyl orpyrimidinyloxymethyl. Examples for alkoxyalkoxyalkyl are methoxyetho,~ylllctl,yl, ethoxyethoxymethyl or propoxyetho~y",clhyl. Examples for alkoxycarbonylalkyl aremethoxycarbonylmethyl or ethoxycarbonylmethyl. Examples for arylalkyl are benzyl, phenethyl, 1-phenylethyl, phenylpropyl, phenylbutyl or the like.

The compounds of formula I contain one or more a~,yll"l,elrical 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 documPnt they are mentioned specifically.
In all other cases mixtures of the isomeric forms are intPn~le-l, 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 ~iPst~ tion~ 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 ;ltt~h~cl form an optionally substituted tetrahydroquinazoline or quinazoline moiety, or Wo 96/17843 PCT/EP~5/04795 b) R, is hydrogen or methyl, or c) R2 is Cl 8alkyl, C, 8alkoxy-C, 4alkyl, C3 8alkenyloxy-C, 4alkyl, or C,.4alkoxy-C~ 4alkoxy-C, 4alkyl.

An even more ~1cf~,.cd subgroup of compounds of formula I enco",~ ses those co11~ounds wherein R~ is hydrogen or methyl, R2 is C, 8alkyl, C, 8alkoxy-C, 8alkyl, C3 8alkenyloxy-C~ 4alkyl, or C~ 4alkoxy-CI 4alkoxy-Cl 4alkyl, and R3 and R4 together form an optionally substituted 1,4-butylene or butadienylene bridge.

~cfellcd 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-tetrahydroquinazolin4-yloxy)-ethyl)-phenyl]-dioxolane, 4-butyl-2-methyl-2-[4-(2-(~1uinazolin-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
R2 R, ~ ~ CH2- CH2- OH (II) wherein R, and R2 are as defined for formula I, with a 4-halopyrimitlin~o of formula m 3 ~ 4 Hal ~N (III) wherein R3 and R4 are as defined for formula I, and Hal is halogen, preferably chlorine or bromine.

The reaction (II + m ~ I) may be carried out in a manner known per se for etherification CA 02206306 1997-0~-28 mPthof1s 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 lelllpel~LLllc is in general between 0~C and the boiling telllperalule of the reaction mixture, preferably is b~Lween room L~ cldlulc and the boiling L~lllpelalul~s of the solvents used.
~ Examples for suitable bases include ~lk~linP. metal hydrides such as sodium hydride, and ~lk~line metal hydroxides such as sodium hydroxide, potassium hydroxide. In the case of ~lk~line metal hydroxides the ether formation is advantageously carried out in the presence of a phase transfer catalyst such as triethylbenzylammonium chloride or bromide (I~EBA), 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 acetonillile; 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 cryst~lli7~tion.

The compounds of formula II may be obtained by hydrolysing a compound of forrnula IV

R2 R, X

'~ ~3CH2--CH2 0 C~y (IV) wherein R, and R2 are as defined for formula I and X is hydrogen, C, 4alkyl, C, 4alkoxy, halo, nitro or cyano, and Y is hydrogen, C, ~alkyl, C, ,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 alk~line hydrolization reactions of carboxylic acid esters. The reaction is preferably carried out in the presence of a base. Advantageousiy 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 . CA 02206306 1997-0~-28 W O96/17843 PCT~EP95/04795 transfer catalyst is being used. In general all types of inorganic bases may be used.
F.l~mples 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 acet~ ing a compound of formula V

R~ 11 ~CH2 CH2 0--C~y (V) wherein R" X and Y are as defined for formula IV with a glycol of formula VI

t ~ H
LOH (VI) wherein R2 is as defined for formula I.

The reaction (V + VI ~ IV) co~lcsponds to a standard acet~lication reaction, which may be conducted in the manner known per se for ~et~ tion reactions. For example the reaction may be catalyzed in the presence of an organic acid or a strong inorganic acid such as conc. sulfuric acid, and the water resulting as one conden~tion product may be separated continuously from the reaction mixture by azeotropic destill~tion. In a typical procedure the reactants of formula V and VI are solved in an inert solvent, suitable for azeotropic d~still~tion, e.g. benzene, toluene, xylene or chloroform, a catalytic amount of toluene sulfonic acid or conc. 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 acet~ ing a compound of formula VII

R, ~ C~--C~-- OH

wherein R" X and Y are as defined for formula IV with a glycol of formula VI

CA 02206306 1997-0~-28 WO 96/17843 PCT~P95/0479 t ~ H
LOH (VI) .

~h~ ;in R2 is as defined for formula I.

The acet~li.c~tion (V~ + VI ~ II) may be con~h~cte~ by a method similar to the described method for obtaining the compounds of formula IV from col~,l)ou,lds of formula V and VI.

The compounds of formula V may be obtained by reacting a coll,l)(Jund of formula v ~CH2--CH2--O ~ (vm) wherein X and Y are as defined for formula IV with an carboxylic acid derivative of formula X

R', I I L ( IX ) wherein R', is C1 4alkyl, Cl 4haloalkyl or C3 6cycloalkyl and L is chlorine or bromine.

The reaction (Vm + IX ~ V) co"~sl)onds 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 re~t~ntc 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 te,.,pe,dture 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

CA 02206306 1997-0~-28 wo 96/17843 PCT~P95/û4795 ~ ~ CH2--CH2- NnH2 ( X ) whrein Rl and R2 are as defined as defined for formula I, with a 4-halo~y, ;~"illine of formula m R3~R4 Hal ~N (III) wherein R3 and R4 are as defined for formula I, and Hal is halogen, preferably chlorine or bromine.

The reaction (X + m ~ I) may be carried out in a manner known per se for the reaction of amines with alkylhalides or heterocyclic h~ les, e.g. of 2-halopyridines or 2-, or 4-halopyrimitlines. 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 isol.lupanol, 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, app.ulJliate are especially sodium hydroxide, potassium hydroxide, sodium carbonate, or potassium carbonate. Reaction tell,pel~tures 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

_o)~CHzCH~ N~j3 (X1) wo 96/17843 PCT/EPgS/04795 whel~in R, 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 phth~limide derivatives. The reaction is preferably carried out in the presence of an amine or hydrazine. For inct~n~e hyd~ e, 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. PlGfe.lcd solvents are alcohols, such as methanol, ethanol or isop,upanol.
Reaction Lt;l"pc;latures are bel~ n 0~C and +100~C, preferably beL~ +20~C and +50~C.

The co,llpoLllds of formula XI may be oL,L~ined by converting a compound of formula XII

_o)43CH2--CH2--Hal ( XII ) wherein R, and R2 are as defined for formula I and Hal is halogen, preferably chlorine or bromine with phth~limide.

The reaction (XII ~ XI) may be carried out in a manner known per se for the alkylation of P.es. T~.e rea~tion is advar.tageously cal.;ed out in the preserlce of z 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
,.

_ o ~ ~ ~ 2 OH

CA 02206306 1997-0~-28 Wo 96/17843 PCTn~P95/04795 W11G1CiII R~ and R2 are as defined for formula I with phth~limi(le The reaction aI ~ XI) may be carried out in a manner known per se for the Mitsunobu reaction (O. Mitsunobu, Synthesis, 1981, p. 1 ff; and DL. ~llghçs, Org. Reaction, 1982, Vol. 42, p. 39~ ff). It is adventageously carried out in the presence of an organo-phosphGIus compound, e.g.
l~ipherlylphosphine~ tritolylphosphine or tributylphosphine and an ~o~ic~rboxylate, for in~t~nce diethyl azodicarboxylate or diisopropyl azodicarboxylate. Preferably the reaction is carried out in an inert organic solvent, e.g. diethyl ether, dioxane or tetrahydlvrulan.

The compounds of formula XII may be obtained by ~ret~ ing a coll.~oulld of formula xm Rl ~ H2 Hal ~

wherein R~ and Hal are as defined for formula XII with a glycol of formula VI

t OH
LOH (VI) wherein R2 is as defined for formula I.

The reaction (Xm + VI ~ XII) co.les~ollds to standard ~cet~ tion reaction, which may be conducied in ihe m~n~ known per se for acer~ rion reactions. ror exampie tne reaction may be cataly~d in the presence of an organic acid or a strong inorganic acid such as conc. sulfuric acid, and the water resulting as one condensation product may be separated continuously from the reaction mixture by azeotropic ~lestill~tion. In a typical procedure the reactants of formula xm and VI are solved in an inert solvent, suitable for azeotropic destillation, e.g. benzene, toluene, xylene or chloroform, a catalytic amount of toluene sulfonic acid or conc. 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.

CA 02206306 1997-0~-28 Wo 96/17843 PCT~EP95/0479~

The int~rmP~i~te compounds of formulae II, IV, V, X, XI and XII are novel, and have espeçi~lly been developed for the plcp~dtion of the active ingredients of formula I.
Thelcrolt;, these compounds belong to the same inventive concepl and thus con~lilule a part of the present invention.

The starting m~t-ori~l~ of form~ e m, VI, VII, vm, IX and X~II are known in the art, or may be ~lcpal~,d according to known methods.

The compounds of formula I are effective against plant-tl~m~ging 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 tests~cent.ration from 0.5 to son mg a.i.A against Uromyces appenr1irn!~t!!~ on pole bear.s, against Puccinia triticina on wheat, against Sphae~theca fuliginP~ on cucumher, 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 hlfe~ s 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 in~iic~tt~d for treatment of plants, seeds and soil to combat phytopathogenic fungi, e.g. Basidiomycetes of the order Ure~in~lPs (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; Deult.ul.,ycetes 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 CA 02206306 l997-0~-28 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, tom~toes or potatoes.

It has been found that the col,lpoullds of formula I are particularly useful for controlling insects, particularly black bean aphids (Aphis fabae), green rice leafhoppers (Nephotettix cinrticeps), mustard beetles (Phaedon cochleariae), and mosquitos (Aedes aegypti). This application therefore provides a method of controlling insects comrricing applying to the insects or their locus an inc~ctici~lly 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 colllpounds of formula I.

The compounds of the formula I are employed in unaltered form, i.e., as a pure sukst~n-~e 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 enc~rsnl~tions 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 circumct~nces 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 (corn), vineyards, pomes and stone fruits (e.g. apple, pears, prunes) and in cereals (e.g. wheat, oats, barley, rlce).

The invention also provides acaricidal, fungicidal and insecticidal compositions, CA 02206306 1997-0~-28 W O96/17843 PCT~EP95/04795 comprising as active ingredient a compound of formula I in association with an agriculturally acceptable diluent (helGil~Ler diluent). They are obtained in conventional llla~ er, e.g. by mixing a co~ ou-ld of the invention with a diluent and optionally additional ingredients, such as surfactants.

The formnl~tions, i.e. the compositions, p-Gpa,dlions or combinations, co~ g theactive substance of the formula I or combinations of this active substance with other fungicides, in~ecti~i~e~ or acaricides, and if desired a solid or liquid additive, are prepared in a known ~-lan-lGr, for example by i,-~ ely mixing and/or grinrling the active substances with diluents, for example with solvents, solid carriers, and, if desired, surface-active coll.poll"ds (surf~ct~nt~).

The compositions can also contain further additives, such as stabilizers, defoamers, preseNatives, viscosity regulators, binders, t~ lçr~ and also fertilizers or other active substances for achieving specific effects.

The term diluent as used herein means liquid or solid agriculturally acceptable m~tPri~l, 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 concenLIdtGs or wettable powders, may contain surfactants such as wetting and dispersing agents, e.g. the condensation product of formaldehyde with naphthalene sulphonate, an alkylaNlsuphonate, a lignin sulphonate, a fatty alkyl sulphate, and ethoxylated alkylphenol and an ethoxylated fatty alcohol.

In general, the formulations include from I 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 concenlldtGs, contain in general from about 5 to 70%, preferably from between 10 and 50% by weight of active agent. Applications forms of forrnulations, e.g. spray suspensions applied to loci of insects and Acarina, contain in CA 02206306 1997-0~-28 Wo 96117843 PCT/EP95/04795 general from 1 ppm to 5000 ppm of a coll-pou,.d 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 applupliate application rates can be determined by outline experiments by those skilled in the art, or by co-,-p~ g the activity of the co--lpou-ld of formula I with standards for which the application rate is known. In general, s~ticf~ctory control of insects is obtained when employing the co-l-pound of formula I at a rate of from abou 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. .S~ticf~ctory 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 Forrnulation 10 Parts of a co,l,poul-d 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.

CA 02206306 1997-0~-28 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 continu~ to obtain a granulate forrn~ tion 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 h~col~Glalion into the soil ~ cent to the plants to be treated.

c. Emulsion Concel.Ll~L~

10 Parts by weight of a colllpuund of formula I are mixed with 10 parts by weight of an emulsifier and 80 parts by weight of xylene. The thus obtained coneenll~te 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 te~llpelatures are in centigrade. Rf values are obtained by thin layer chromatography on silica gel, unless otherwise specified.

~xample 1: 4-Allyoxymethyl-2-methyl-2-r4-(2-(quinazolin4-yloxy)-ethyl-phenyll-dioxolane ~ ~ C H2- C H2- O ~ N

a) 4-acetylphenylethyl benzoate o H3C ~ CH2- CH2 O - C

CA 02206306 1997-0~-28 Wo 96/17843 PCT/EP95/04795 263 g (2.0 mole) of anhydrous alu~ -"~ chloride are suspended in 1800 ml dichlorometh~ne. After the ~ Lulc 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 telllpc~ ul~ and then poured into a mixture of 500 ml crushed ice and 900 ml conc. hydrochloric acid. After separation of the phases, the aqueous layer is extracted with 2 x 400 ml dichlolul"rll-~nt . The combined organic layer is washed with water and 10% aqueous potassiulll hydrocarbonate solution, dried over m~n~ium sulfate and evaporated in vacuum. The residue is lecl~ 11i7~d from an ethyl~cet~t~/hexane llli~Lule. Yield: 165 g of 4-acetylphenylethyl bel-70;~le, m.p. 90.5 - 91.5~C.

b) 2-r4-(4-allvloxyl'nethyl-2-methyl-dioxolan-2-yl)-phenyll-ethyl benzoate ~\[ o~ CH2--CH2 ~--CO~

203 g (0.75 mole) of 4-acetylphenylethyl ben70at~ 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 ~ ml ~f a 10% a~de~us p~tassiun~ c~}b~r~at~ s~ld~n, dr~ ver mCd~
sulfate and evaporated in vacuum.
Yield: 272 g of 2-[4-(4-allyloxymethyl-2-methyl-dioxolan-2-yl)-phenyl]-ethyl benzoate.

c) 2r4-(4-allyloxymethyl-2-methyl-dioxolân-2-yl)-phenyll-ethânol ~ ~ CH2 CH2 OH ''=

CA 02206306 1997-0~-28 W O96/17843 PCT/~101795 5.0 g (13 mrnole) 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 tel,lpc.dtu-c. The mixture is evapolated to the half of the volume, diluted with 100 ml water and extracted with 3 x 100 ml diethyl ether. The col,lbincd organic layer is washed with 100 ml water, dried over m~ ", sulfate and ev~po,ated in vacuum. The residue is chromatogr~rhe(l 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 telllpclalult and cooled again to 0~C. 2.3 g (14 mmole) 4-chloroquin~oline are added in portions. The reaction "~ U~c is stirred for 3 hours at room Iclllp~,lalulc, then cooled to 0~C and added dropwise. Subsequently the ll~i~lulG is extracted with ethyl acetate. The organic layer is dried over m~gn~cillm sulfate and evapo,ated 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-(quinazolin4-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 sodiumhydroxide solution, 11.4g of TEBA (triethylbenzyl ammonium chloride) and 131.6g of 4-chloroquinazoline in portions. The mixture is stirred for 5 hours at room lclllpc~atulc, then extracted with diethylether, and washed with water and brine. The organic layer is dried over m~gnPsium 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-(quina~olin-4-yloxy)-ethyl)-phenyl]-dioxolane,m.p. 62 - 64~C.

Wo 96/17843 PCTi~;l 9~/01795 ~ Example 2: 4-Formylphenylethyl benzoate H ~ CH2 CH~ O C ~

To a stirred solution of phenylethyl benzoate (45.2 g, 0.2 mole) in dichlo~ nP
(140 ml) is added at 0~C tit~nium tekachloride (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 HCI-gas takes place during warm up to room telllpelalulc. The reaction llli~lulc; is stirred over night at room tem~,ldLulc;. The brown mixture is then slowly poured into crushed ice, extracted with dichlc,l~ h~n~, and the extracts are washed with water, saturated pot~si~lm bicarbonate solution and brine. The combined organic layer is dried over m~g"~ciulll sulfate and the solvent removed in vacuum. Column elllulllalography on silica gel (eluant: hexane/ethyl acetate, 9:1) first yields some starting material; and la~ter 25.3 g Qf pu~ 4-f~l~en~lethyl b~.7O~t~ m.p. 54c56~~

Example 3 4-B utyl-2-methyl-2-r4-(2-(S-çhloro-6-ethylpyl hllidin-S -ylamino)-ethyl)-phenyll -dioxolane ~o~CH2~ NH~

a) N-r4-(4-butyl-2-methyl-dioxolan-2-yl)-phenylethyll-phthalimide --~ ~3CH2 CH2 N~3 To a solution of 9.S 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) phth~limide in 400 ml tetrahydrofuran is added dropwise 7.3 g (42 mmole) CA 02206306 1997-0~-28 Wo 96/17843 PCTll~P95/04795 diethyl ~o-lic~rboxylate. The reaction is stirred for 1 hour at room telllp.,.dLur~. The solvent is removed in vacuum and the residue is taken up in a ether/hexane lllh~Lul~. The resulting precipitate is washed with an ether/hexane l~ Ul~. 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] phth~limi(le b) 2-r4-(4-butvl-2-methyl-dioxolan-2-yl)-phenyll-ethylamine ~ >~CH2--CH2 NH2 4.0 g (10 mmol) N-[4-(4-butyl-2-methyl-dioxolan-2-yl)-phenylethyl]-phth~limide are suspended in 40 ml ethanol. 40 ml of a methylamine solution (33% in ethanol) are added slowly. The reaction mi~lul~ is stirred for 3 hours at room lellll)eldtul~. Subsequently the mixture is evapolated 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 m~gne~ium 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 de-si~n~tes phenyl.

~ ~, rA ~ ~ ~ ~ _ C_ C:
S ~_ 'v X X ~ a~ X X

~ ii 0~

~ O O O OO O

ir~ X'~

5 ,~ 5 V ~ V

-- o o o, o o. o o W O96/17843 PCT~EP95/04795 ~ ~ _ _ _ -- ~ ~ _ _ C ~ ~ ;~'~ C ~ C
X X X ~ ~ ~ X X X X ~ X

~t O
~ ~ ~ o o o ~ o o o o o o ~ o o - o & CL
E E c o o o o o o o o o o o o 5N c~ ~ 5 ~J _ 5N

X~ ~ X

~ X C~ O_ ~ ~ ~ U- ~ t-- ~
O O O

WO 96/17843 PCT/~;l 95/01795 .. .. .. .. .. .. .. ..

s s ,~ s s s s~s~ s C,~
C ~ C ~
X ~ X X X ~,, X X C~ s ~- ~ s .c ~ s s X ~ ~ ~ o ~ Cr~
o O o o 0 11 0 11 0 0 0 0 E C c oooooooo o ooo~

.~. .. . .

~ ~ ~ 5~ e 5~ ~ 5~ 5- 5o ~ ~ 5~

r5r-') r-~
5~ 5~ ~ ~ T ~'' X ~ V
~_ ~ 5. 5 ~

o~ o -- ~ ~ ~ ~ ~ 1-- oo ~ o _ -W O96/17843 PCTAEPg5/04795 c E J~ ~ ~ --c ._ s s s s '~ C ~ ~ C
~ ~ S S S S
o o ~, o ~ o ~
--oooo :C X
Z ~ o o o o L

~) X ~ ~

~ ~ . _ D J I z O O

. CA 02206306 1997-05-28 W O96/17843 PCT~EP95104795 .. .. .. .. .. .. .. .. .. .. .. .. ..

_ ~ g _, _ ~ ~ s ~
~i C r C~ c C~ - c ~ ~~
x X x x X x x X K K ~
~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ K K

0 1-- 0 0 ~ o~ ~ ~ ~ -- ~ ~o O O O O o O O o O O O O O

O O O O O O O O O O O O O

U ~ U V ~ ~ :L

~ ~' 5' 5' 5 ~ ~ 5 5' 5 ~ ~ 5 V ~ ~ ~ ~ ~ 5 t-- oo ~ O
OOoOo----______ E E ,~ ~ E ~ _ ~

~~ E~ ~ _ E ~ ~~ ~

a ~ X ~ E ~ ~ t ---- E s s E ô ~ ~~ E _ ~ ~ ~ E _ ~
Z _ ~ ~ _ Z _ u~ ~ _ Z _ x ~ ~ cr~
~ :C _ '~ X ~ ~ ~ ~ E~ ~
~ _ _ ~ _ ~ ~ ~ ~ _ ~ ~ ~ _ o o o o o Z Z

U 5~5~ 5 U U

a ~~ ~

X ~ O
C'l ~ C'~

.. .. .. .. .. ..

o c c ~ C C c ~;
~, CC~ CCCC
c XK ~ X K X X

O O O . O O O O
E

oooooooo " U U ~ _' S

~ r5 r~l r'l r') ~ r'- r' r"

- o o oo o o o o o o o ~, z ~ ~ ~ ~ ~ ~ ~ ~

.. .. .. .. ..

~ ~ K X
S ~

C C K K

O
O ~ O O 0 11 0 C

O O O O O O Z Z
.

.

O O
~ V

U C~ ~ V

X

O

,_ _ _ _ _ _ _ _ _ ,~ C C C
X K X C C C

t_ -- ~ ~ ~O X t-- ~
O O O O O O O

O O O O O O O
~ ~ X '' ~"
V ~ V
V ~ ~ V

O O O O O O

Sl - ~ o o o o o o ~ o - _ S ~ ~ _ 8 ~: ~ '' C ~:: C '~
X X X X ~ X X ~ X ~ X X X

cr oo ~o O ~ ~ ~ ~ -- r~ x oo ~ ~
O O O O O O O O O O O O O O

OOOOOOOOZZZZZZ
r~) ~ r'~ r~ r~~ r~
~,~ o o o o O o o ~,~ o ~)~ ~~
~ X ~ X ~
C~VVV~;VV VVV~, r -r ~ r~ r~ ~ r~ ~
V o o oo O ov o o V V V

~:'' ~"' . .
V .~ ~, , 5 ~ ~~ Vl ~ G

, V 3 ~ 3 ~ 2 v ~~ ~~ ~~ ~~ ~) ~~ ~~ v ~~ v v ~) v oo o~ o _ ~ ~ ~ ~ ~ t~ o o. o__________~

c '--- C
C C~ C
X XX X
,c c 't _ ~
o o o O

Z Z Z Z
5 ~ I

CL, Z --' ~, ~) V

O
X~

V

CA 02206306 1997-0~-28 W O96/17843 PCT~EP9S/04795 Table 5:

_ o) ~ CH2 CH2 OH

No. R, R2 physical data Rf system 5.01 H CH2OCH2CH=CH2 0.09he~anc/ethyl acetate, 7: 3 5.02 CH3 H 0.10hexane/ethyl acetate, 7: 3 5.03 CH3 CH3 0.06hexane/ethyl acetate, 7: 3 5.04 CH3 CH2CH3 0.17hexane/ethyl acetate, 7: 3 5.05 CH3 CH2CH2CH3 5.06 CH3 CH2CH2CH2CH3 0.25hexane/ethyl acetate, 9: 1 5.07 CH3 CH2CI 0.15hexane/ethyl acetate, 7: 3 5.08 CH3 CH2OCH3 5.09 CH3 CH2OCH2CH=CH2 0.08/hexane/ethyl acetate, 7: 3 0.15 5.10 CH3 CH2OCH2C(CH3)=CH2 007/hexane/ethyl acetate, 7: 3 0.15 5.11 CH3 CH2OCH2C(CI)=CH2 0.07/hexane/ethyl acetate, 7: 3 0.13 5.12 CH3 CH2OCH2CH=CHCH3 5.13 CH3 CH2OCH2CeCH

CA 02206306 1997-0~-28 Wo 96/17843 PCT/EPg5/04795 5.14 CH3CH2SCH3 5.15 CH3 CH2O(4-CI-)Ph 0.20hexane/ethyl acetate, 7: 3 5.16 CH3CH2O(2-CH3O-)Ph 5.17 CH3 CH2OCH2Ph 5.18CH2CI H
5.19CH2CH3 CH2OCH2CH=CH2 5.20CH2CH3 CH20CH2eCH
5.21CH2CH2CH3 H . 0.10hexane/ethyl acetate, 7: 3 5.22CH2CH2CH3 CH2CH3 0.07/hexane/ethyl acetate, 7: 3 0.13 5.23CH2CH2CH3 CH2OCH2CH=cH2 0.10/hexane/ethyl acetate, 7: 3 0.18 5.24 CH3 CH2SCH2CH3 5.25 CH3 Ph 0.30hexane/ethyl acetate, 1: 1 5.26 CH3 CH2CH2Ph 5.27 CH3 n-C6H~3 0.23hexane/ethyl acetate, 7: 3 5.28 CH3 n-C8HI7 0.22hexane/ethyl acetate, 7: 3 5.29 CH3 n-C,OH2, 0-40hexane/ethyl acetate, 1: 1 5.30 CH3 CH2OCH(CH3)2 0.10hexane/ethyl acetate, 7: 3 W O 96/17843 PC~rAEP95/0479S

Table 6: ~ :

~o)L~cH2-cH2 ~~

N o. Rl R2 X Y physical data Rf syste m 6.01 H CH2OCH2CH=cH2 H -H 0.29hexane/ethanol,9S:S
6.02 CH3 H H H m.p.69-70~C
6.03 CH3 CH3 H H 0.55hexane/ethanol,95:5 6.04 CH3 CH2CH3 H H 0.52hexane/ethyl acetate, 7:3 6.05 CH3 CH2CH2CH3 H H 0.46hexane/ethyl acetate, 6.06 CH3 CH2CH2CH2CH3 H H 0.20/hexane/ether,9:1 0.24 6.07 CH3 CH2CI H H 0.39hexane/ethyl acetate, 6.08 CH3 CH20CH3 H H 0.25/hexane/ethanol,95:5 0.30 6.09 CH3 CH2OCH2CH=CH2 H H 0.26/hexane/ethyl acetate, 0.30 7:3 6.10 CHl CH20CH2C(CH3)=CH2 H H
6.11 CH3 CH20CH2C(CI)=CH, H H
6.12 CH3 CH20CH2CH=CHCH3 H H

SlJBSTlTUTE S~EET (RULE 2~) CA 02206306 1997-0~-28 W 096/17843 PCT/~l55lo~795 6.13 CH3 CH2OCH2C_CH H H
6.14 CH3 CH2SCH3 H H
6.15 CH3 CH2O(4-C1-)Ph H H 0.47/hexane/ethyl acetate, 0.49 7:3 6.16 CH3CH2O(2-CH3O-)Ph H H
6.17 CH3 CH2OCH2Ph H H
6.18 CH2CI H H H
6.19CH2CH3 CH2OCH2CH=cH2 H H
6.20CH2CH3 CH2OCH2C_CH H H
6.21CH2CH2CH3 H H H 0.23hexane/ethyl acetate, 9:1 6.22CH2CH2CH3 CH2CH3 H H 0.24/hexane/ethyl acetate, 0.30 7:3 6.23CH2CH2CH3 CH2OCH2CH=CH2 H H 0.42/hexane/ethyl acetate, 0.48 7:3 6.24 CH3 CH2SCH2CH3 H H
6.25 CH3 CH2OCH(CH3)2 H H 0.35hexane/ethyl acetate, 7:3 W O96tl7843 PCT~EP9S/04795 Table 7:

~~

No. R, X Yphysical data m.p. (~C) 7.01 H H H 54-56~C
7.02 CH3 H H90.5-91.5~C
7.03 CH2CI H H
7.04CH2CH3 H H
7.05CH2CH2CH3 H H 56-58~C

CA 02206306 1997-0~-28 Wo 96/17843 PcTlEpsslo4795 Table 8 R2_o~

No. Rl R2 physical data Rf system 8.01 CH3CH2OCH2=CH2 0.15 hexane/ethyl acetate, 7:3 8.02 CH3CH2OCH2C(CH3)=CH2 0.15 hexane/ethyl acetate, 7:3 8.03 CH3CH20CH2C3CH 0.2 hexane/ethyl acetate, 7:3 8.04 CH3CH20(3-CF3)Ph 0.25 hexane/ethyl acetate, 7:3 8.05 CH3CH20CH2(2-CN)Ph 0.2 hexane/ethyl acetate, 7:3 8.06 CH3CH2CH2CH2CH3 0.2 hexane/ethyl acetate, 7:3 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 (black bean aphids 2 days before treatment, potted broad bean plants (Vicia faba). were infested with adults CA 02206306 1997-0~-28 wo 96/17843 PCT/EP95/04795 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 t~ t~ the efficacy was measured by co..lp;1~;ng the honeydew production with that of the u~ ;dl~d check. 8 days after treatment, a visual estim~t~ of the llulllbci, of surviving insects was used to calculate the efficacy in %, according to Abbott.
In this test colllpounds 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 mgAiter.

b) Nephtottix cincticeps (~reen rice leafhopper) Rice plants (Oryza sativa) were sprayed with 1 concentration, 500 mg a.i./liter, using a spray tunnel (1 plant per con~entr~tion). 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 tre~tm~o-nt, the llulllbel 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, 3.11, 3.12, 3.15, 4.12, 4.13, 4.16, 4.17 and 4.18 showed an efficacy of 90% or more at 500 mgAiter.

c) Tetranvchus 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 tre~tmPnt 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, 3.11, 3.12, 3.15, 3.1-6, 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 mgAiter after 8 days.

CA 02206306 1997-0~-28 wo 96/17843 PCT/~ /0 l795 Residual Contact Action Phaedon cochleariae (mustard beetle) 10 adult insects of Phaedon cochleariae (Coleoptera, Chrysom~ 7 mustard beetle) are L;ollrlned in plastic Petri dishes (9 cm/~i~m~ter) previously sprayed in a spray tunnel.
2 concentrations are applied (500 and 100 mg a.i./liter spray dilution). Mortality in %
(with Abbott correction) is detellllined 2 days after the tre~tm~-nt In this test co,llpounds 1.13, 1.20 and 3.02 showed an efficacy of 90% or more at 500 mg/liter.

Ovicidal Action Tt;~lallvcl~us urticae (two-spotted spider mite) 5 to 7 adult females of Tellallycllus urticae are conrlned in a glue ring of 2 cm ~ mPter on the upper side of bush bean leaves (Phaseolus vul~a~is) 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 unh~tl~-hed eggs, is c~lcul~t~d 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.

Fun~icidal Tests a) Activity against Powdery Mildew Sphaerotheca filligin~a Plants of Cucumi~ sativus (cucumber), 7 days old (cotyledon stage), are sprayed to near run off with a suspension cont~ining 250 mg/l of active ingredient. The deposit is then allowed to dry. One day later, the treated plants are inocul~tt-d with a spore suspension cont~ining lxlO5/ml of freshly collected conidia of Sphaerotheca filligin~a 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 CO"~p~ g the degree of fungal CA 02206306 1997-0~-28 Wo 96/17843 PCT/EPg5/0479 attack with that on u~ ,ated, ~imil~rly inocul~t~d check plants. In this test compounds 1.02, 1.03, 1.05, 1.07, 1.09, 1.11, i.12, i.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 col~lpoLlllds against the following pathogens:
Podos~a~la leucotricha on apple, Erysiphe grmini~ on wheat and barley (dry inoculation), Uncinula necator on grape.

b) Activity against Rush, Scab, Pyrenophora, L~losph~P,ria Ul~lllyces appe~lic~ tllc:
Plants of Phaseolus vulgaris (pole bean), 14 days old (2 leaves stage), are sprayed to near run off with a ~ùspension col,~ining 250 mg/l of the active ingredient. The deposit is then allowed to dry. One day later, the treated plants are inoc~ t~d with a spore suspension cont~ining lxl05/ml of freshly collected spores of Uromyces appendic-ll~hls Tnr~lb~tion is performed for 3 days in a high humidity cabinet at 23~C and >95% r.h. and thelc;aflc during 10 days at +24~C and 60% r.h.
The efficacy the colllpoullds is determined by COlllpalillg the degree of fungal attack with that on untreated, similarly inoculated check plants. In this test colllpoullds 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, 3.11, 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 CA 02206306 1997-0~-28 wo 96/17843 PCTIEP95/04795 a spray suspension contAining 250 mgA of the active ingredient. The deposit is then allowed to dry. 1 day later, the treated plants are inocul~tt~cl with a spore suspension c~ g lxlO5/ml of freshly collected sporangia of Phytophthora infestans and the incubAtt~cl for 7 days in a high humi~lity cabinet at +18~C and >95% r.h. The efficacy of the test co~ oullds is ~lele~ ci by co-~pA~ing the deg~ee of fungal attack with that on untreated, simil~rly inoculAtecl check plants. In this test collll~oLlnds 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 COIllpC unds against Plasmopara viticola on grape vine.

d) Activity after Seed T1CAIIIIt.I~l The colllpoullds of the invention may also be used for seed treAtm~ t The advantageous fungicidal activity is established by in vitro tests with the following pathogens:
Pyrenophora grAmin~A
Ustilago nuda, Gerlachia nivalis, Lepto~hpaeria nodorum.
Autoclaved wheat seeds are inoculated with spores or mycelium of the pathogens and coated with dir~c.cnt concentrations of the test compound resulting in dosages of 50g a.i./lOOOkg 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 treAtm~q-nt and untreated inocul~te~ 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 seerlling.

Claims (21)

Claims:

1. A 2-[4-(2-(pyrimidin-4-yloxy- or -4-ylamino)-ethyl)-phenyl]-dioxolane of formula I

(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-C1-4alkyl, 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.

2. A compound according to claim 1 wherein R3 and R4 together form an optionallysubstituted 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

(II) or a 2-[4-(2-aminoethyl)-phenyl]-dioxolane of formula X

(X) wherein R1 and R2 are as defined for formula I in claim 1, with a 4-halopyrimidine of formula III

(III) 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 acompound 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

(II) 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

(IV) 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

(IV) 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

(V) wherein R1, X and Y are as defined for formula IV in claim 12 with a glycol of formula VI

(VI) wherein R2 is as defined for formula I in claim 1.

14. A compound of formula V

(V) 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

(VII) wherein R1, X and Y are as defined for formula IV in claim 12 with a glycol of formula VI

(VI) wherein R2 is as defined for formula I in claim 1.

16. A compound of formula X

(X) 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

(XI) wherein R1 and R2 are as defined for formula I.

18. A compound of formula XI

(XI) 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

(II) wherein R1 and R2 are as defined for formule I in claim 1 with phthalimide.

20. A compound of formula XII

(XII) 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

(XIII) wherein R1 and Hal are as defined for formula XII in claim 20 with a glycol of formula VI

(VI)