ZA200210070B - Fungicidal 5-phenyl substituted 2-(cyanoamino) pyrimidines. - Google Patents

Description

*

FUNGICIDAL 5-PHENYL SUBSTITUTED 2-(CYANOAMINO) PYRIMIDINES

The present invention relates to pyrimidines of formula I rt

X

2

R

4

R x oN NTRS

CN in which

R! represents hydrogen or

C1-Cio-alkyl, Ci1-Cig-haloalkyl, C;-Cg-alkenyl, Cp-Cg-alkynyl,

C4~-Cg-alkadienyl, C;-C;p-alkoxy, C3-Cg-~cycloalkyl, phenyl, or 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclyl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom, or tri-Cy~-Cg-alkyl-silyl, formyl or C;-Cjp-alkoxycarbonyl; wherein R! groups are unsubstituted or substituted by one to three groups R?2

R2 halogen, nitro, cyano, hydroxy or ’ C;-Ci9-alkyl, C3-Cg-cycloalkyl, C3-Cg~cycloalkenyl,

C1-Cjo-haloalkyl, C;-Cg¢-halocycloalkyl, C;-Cjp-alkoxy,

C1-Cig-haloalkoxy, C3~Cig-haloalkoxy, C;-Cg-alkoxycarbo- nyl, tri-C;-C4-alkylsilyl, phenyl, halo- or dihalo-phenyl or 5- or 6-membered heteroaryl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom;

R? represents phenyl, C3-Cg-cycloalkyl or 5- or é6-membered heteroaryl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom, which are 40 unsubstituted or substituted by one to three groups R®;

R3 represents hydrogen, halogen or

C1-Cy p-alkyl, C;-Cjp-alkoxy, Ci;-Cjp-alkylthio, C;-Cjp-alkylamino 45 or di-C;-Cjg—-alkylamino; which are unsubstituted or substitu- ted by one to three groups R23;

: AMENDED SHEET a WO 01/96314 PCT/EP01/06565 [5 2 ® R* represents hydrogen or

C,-C,o-alkyl, C,-C,-alkenyl or C,-C,-alkynyl; which are unsub- stituted or substituted by one to three groups R®; and

X represents 0, S, NR’ or a single bond, wherein

R® represents hydrogen or C,-C,,-alkyl; or } R' and R® together with the interjacent nitrogen atom form a heterocyclic ring.

Moreover, the invention relates to processes and intermediates for preparing these compounds, to compositions comprising them and to their use for controlling harmful fungi.

In Vestn. Slov. Kem. Drus. (1986), 33(3), 353-66 (ISSN: 0560-3110, CAN 107:39701) it is disclosed that the reaction of

N-pyrimid-2-ylformamide oximes with N,N-dimethylformamide diethyl acetal yields 2-(N-cyano-N-ethylamino)pyrimidines. In J. Org.

Chem. 39 (9) 1256-1252 (1974) N-glycosylated 2-(N-cyancamino) py- rimidines are disclosed and in US 4,711,959 a process for the preparation of 2-(N-cyanoamino) pyrimidines is described.

A need exists to provide fungicidal compounds having improved activity.

We have found that this need is fulfilled by the compounds defined at the outset. Furthermore, we have found processes for their preparation, compositions comprising them and methods for controlling harmful fungi using the compounds I.

Compounds of formula I wherein R* is an optionally substituted alkyl, alkenyl or alkynyl group as defined above may be obtained by treating a compound of the formula II ® . rR?

Bi EN IT — “ R? : 40 in which R' through R’ and X are as defined in formula I; with a strong base and an alkylation agent of formula III

Ré-Y 45 III in which R? is C;-Cg-alkyl, C;-~Cg~alkenyl or C;-Cg-alkynyl; which are unsubstituted or substituted by one to three groups R2, and Y represents a nucleophilic replaceable leaving group, preferably a halogen atom, in particular a iodine atom. . 5 . Compounds of formula II are known for example from US 5,593,996, < WO-A 98/46608, FR-A 2,765,875, WO-A 99/41255 or WO-A 99/48893.

The reaction between the triazolopyrimidines of formula II, the strong base and the alkylation agent of formula III is preferably carried out in the presence of an inert solvent. Suitable sol- vents include ethers, such as dioxane, diethyl ether and tetra- hydrofuran, halogenated hydrocarbons such as dichloromethane, amides, such as dimethylformamide or N-methylpyrrolidone and aro- matic hydrocarbons, for example toluene or mixtures of these sol- vents. The reaction is suitably carried out at a temperature in the range from -78 °C to 100 °C, the preferred reaction temperature is from 10 °C to 80 °C, particular at ambient temperature.

Suitable strong bases include metal hydrides, such as sodium hydride, potassium hydride or calcium hydride, and metal amides, such as sodium amide, potassium amide, lithium diisopropylamide or potassium hexamethyldisilazide, and metal alkanes such as methyllithium, n-butyllithium or tert-butyllithium.

Furthermore, the compounds of formula I wherein R* is an optio- nally substituted alkyl, alkenyl or alkynyl group may be prepared by reacting a N-pyrimid-2-ylformamide oxime of formula IV

X—R

RY N-— 0p / R? Iv = in which R! through R3 and X are as defined in formula I; with a

N,N-dimethyl formamide dialkyl acetate of formula V

HC OR* w—( v a,c OR* » 40

Ca in which R% is is C;-Cg-~alkyl, C;-Cg-alkenyl or C;-Cg-alkynyl; which are unsubstituted or substituted by one to three groups R2. t

The reaction between the compounds of formula IV and the 45 compounds of formula V can be carried out analogosly to the reaction described in Vestn. Slov. Kem. Drus. (1986), 33(3), 353-66. :

Compounds of formula I wherein R? is hydrogen can preferably be prepared by treating sulfones of formula VI «® . 5 er v1

Y NN R’ in which R! through R3 and X are as defined in formula I and RS is C;-Cg-alkyl or C;-Cg-haloalkyl; with cyanamide or with a metal salt of cyanamide. The use of a base and/or a solvent can be ad- vantageous.

This process is preferabfy carried out in the presence of an in- ert solvent. Suitable solvents include aromatic hydrocarbons, such as, for example toluene or xylene, chlorinated hydrocarbons, such as, for example methylene chloride, chloroform, a chloroben- zene, ketones, such as, for example acetone, methyl ethyl ketone, methyl isopropyl ketone or methyl isobutyl ketone, nitriles, such as, for example acetonitrile or propionitrile ethers, such as, for example diethyl ether, diisopropyl ether, methyl tert-butyle- ther, dimethoxyethane, tetrahydrofuran or dioxane, amides, such as, for example, dimethylacetamide or diethylacetamide, sulfoxi- des, such as, for example dimethylsulfoxide or sulfolane, or mix- tures thereof.

The use of a base can be advantageous in this reaction. Suitable bases include alkali metal hydrides and earth alkaline metal hy- drides, such as, for example, sodium, potassium or calcium hydri- des, alkali metal hydroxides and alkaline earth metal hydroxides, such as, for example, sodium, potassium or calcium hydroxides, alkali metal carbonatesand alkaline eath metal carbonates, such as, for example sodium carbonate, potassium carbonate or calcium carbonate, alkali metal bicarbonates and alkaline earth metal bi- carbonates, such as sodium bicarbonate, potassium bicarbonate or calcium bicarbonate, metal amides, such as, for example sodium amide, potassium amide, lithium diisopropylamide or potassium he- xXamethyldisilazide, metal alkanes, such as for example methyl lithium, n-butyl lithium or tert-butyl lithium or aprotic amines, " 40 such as, for example pyridine, tributylaine, N,N-dimethylbenzyl- amine or diazobicycloundecene. f Various qualities of cyanamide may be employed for the process.

The use of an aqueous solution of cyanamide may be preferred for 45 practical reasons. The use of metal salts of cyanamide, potassium cyanamide, dipotassium cyanamide or calcium cyanamide is also possible. -

Dependant an the used cyanamide or salt of, cyanamide and depen- dant on the base an appropriate solvent is employed.

The reaction is suitable carried out at a temperature in the . 5 range from -78°C to reflux temperature, the preferred reaction temperature is from 0°C to 150°C, particular at ambient q temperature.

In general 1 to 3 equivalents, preferably 1.5 to 2.5 equivalents of base are employed per equivalent of sulfone of the formula VI.

Generally 2 to 6 equivalents, preferably 3 to 5 equivalents of cyanamide or salt of cyanamide are employed per equivalent of the sulfone of the general formula VI.

Compounds of formula I wherein RY is is C;-Cg-alkyl, C;-Cgz-alkenyl or C;-Cg-alkynyl which are unsubstituted or substituted by one to three groups R2 may be prepared by alkylation of compounds of for- mula I wherein R? is hydrogen with an alkylation agent of formula

IIT.

The use of a base can be advantageous in this reaction. Suitable bases include alkali metal hydrides and earth alkaline metal hy- drides, such as, for example, sodium, potassium or caicium hydri- des, alkali metal hydroxides and alkaline earth metal hydroxides, such as, for example, sodium, potassium or calcium hydroxides, alkali metal carbonates and alkaline earth metal carbonates, such as, for example sodium carbonate, potassium carbonate or calcium carbonate, alkali metal bicarbonates and alkaline earth metal bi- carbonates, such as sodium bicarbonate, potassium bicarbonate or calcium bicarbonate, metal amides, such as, for example sodium amide, potassium amide, lithium diisopropylamide or potassium he- xamethyldisilazide, metal alkanes, such as for example methyl lithium, n-butyl lithium or tert-butyl lithium or aprotic amines, such as, for exampie pyridine, tributylaine, N,N-dimethylbenzyla- mine or diazobicycloundecene.

The alkylation is preferably carried out in the presence of an inert solvent. Suitable solvents include aromatic hydrocarbons, ™ 40 such as, for example toluene or xylene, chlorinated hydrocarbons, such as, for example methylene chloride, chloroform, a chloroben- zene, ketones, such as, for example acetone, methyl ethyl ketone, ) methyl isopropyl ketone or methyl isobutyl ketone, nitriles, such as, for example acetonitrile or propionitrile ethers, such as, 45 for example diethyl ether, diisopropyl ether, methyl tert-butyle- ther, dimethoxyethane, tetrahydrofuran or dioxane, amides, such as, for example, dimethylacetamide or diethylacetamide, sulfoxi-

des, such as, for example dimethylsulfoxide or sulfolane, or mix- tures thereof.

The reaction is suitably carried out at a temperature in the : 5 range from -78°C to reflux temperature, the preferred reaction temperature is 0°C to 150°C, particular ambient temperature. 4 in general 0.8 to 5 equivalents, preferably 0.8 to 4.5 equiva- lents of the alkylation agent of the formula III are employed per equivalent of the compound of formula I.

Usually 0.8 to 3 equivalents, preferably 0.8 to 2.5 equivalents of base are employed per equivalent of the compound of formula I. 1t is also possible to prepare compounds of formula I wherein R% is is C;-Cg-alkyl, C;-Cg-alkenyl or C;-Cg-alkynyl which are unsub- stituted or substituted by one to three groups R2 by reacting a sulfone of formula VI 1 xR 2 04 VI

NPN rR’ in which R! through R3 and X are as defined in formula I and R® is

C1~-Cg-alkyl or C;-Cg-haloalkyl; with an alkylated cyanamide of formula VII

RL___CN VII i wherein R% is is C;-Cg¢-alkyl, C;~Cg-alkenyl or C;-Cg-alkynyl which are unsubstituted or substituted by one to three groups R2®. The use of a base and/or a solvent can be advantageous.

Suitable bases and solvents are such as listed at the reaction with cyanamide.

The reaction is suitable carried out at a temperature in the = 40 range of from -78°C to reflux temperature, the preferred reaction temperature is from 0°C to 150°C, particular at ambient

B temperature.

The reaction is in general carried out under usual pressure. 45 :

In general 1 to 3 equivalents preferably 1.5 to 2.5 equivalents of base are employed per equivalent of the sulfone of formula VI.

Usually 2 to 6 equivalents, preferably 3 to 5 equivalents of’ alkylated cyanamide of formula VII are employed per equivalents of the sulfone of formula VI. , 5 Sulfones of the formula VI are obtained by reacting 2-thiopyrimi- dinederivatives of the formula VIII n LR

R’ VIII x

R®—5~ NT TR’ in which the variables are as defined in formula VI; with oxidi- zing agents, such as, for example m-chloroperbenzoic acid, per acetic acid, trifluoro per acetic acid, chlorine water, hypocho- rous acid or metal salt solutions thereof in water or hydrogen peroxide, if appropriate in presence of a catalyst, such as for example wolframate.

If appropriate solvents, such as for example, methylene chloride, chloroform, carbontetrachloride, 1,2-dichloroethane or chloroben- zene are used at temperatures of -20°C to reflux.

The 2-thiopyrimidine derivatives of the formula VIII may be ob- tained when 6-halo-2-thiopyrimidines of formula IX

Hal

Rr?

A IX rome rR? in which the substituents are as before mentioned and “Hal” deno- tes halogen; are reacted with a nucleophile of formula X

H-X-R! X wherein R! and X are as defined in formula I, if appropriate in the presence of a suitable base and if appropriate in an organic . 40 solvent. The solvents and bases employed are similar to those mentioned for the preparation of the compounds of formula I. * 6-halo~2-thiopyrimidines of formula IX are known in the art or may be prepared according following reaction sequence:

o o S 0 “R J Rr’ ° XI HN" TNH, om XII

R? ~R —_— A

S § 0] : 5

OH

% alkylation R?

XII —_ XIII 6 Js - So R*—87 SN “oH

Hal halogenation R?

XIII —_— XIV

NIN Hal

Hal

Rr?

XIV —_— Ie XI

NN

Rr — r3

S N

(R2, R3 and R® are as defined above and R is an alkyl group) The reaction conditions are in general known in the art.

Base catalyzed reaction of dialkylmalonate with thiourea affords 2-thiobarbituric acid XII which may be selectively alkylated on sulfur to yield XIII.

Halogenation, preferably chlorination or bromination, especially chlorination, with for exaple phophorous oxychloride or phospho- rous oxybromide in the presence of a tertiary amine base then af- fords the dihalo derivative XIV.

Subsequent introduction of the radical R3, if appropriate, via nucleophilic substitution affords the 6-halo-2-thiopyrimidine of formula IX.

Sulfones of formula VI and 2-thiopyrimidine derivatives of for- mula VIII are novel. 10 40 In the symbol definitions given in the formulae above, collective terms were used which generally represent the following substi- . tuents: ~ halogen: fluorine, chlorine, bromine and iodine; 45 . - C3-Cg-alkyl and the alkyl moieties of C;-Cg-—alkoxy,

C;-Cg-alkylthio, C1-Cg-alkylamino, di-C;-Cg-alkylamine or

C;-Cg-alkoxycarbonyl: saturated, straight-chain or branched hydrocarbon radicals having 1 to 6 carbon atoms, preferrably

Ci1-Cs-alkyl, such as methyl, ethyl, propyl, l-methylethyl, butyl, l-methylpropyl, 2-methylpropyl, 1,l1-dimethylethyl; or pentyl, - 5 l-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-di-methylpropyl, l-ethylpropyl, hexyl, 1,l-dimethylpropyl, 1,2-dimethylpropyl, . l-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, ) 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, l-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, l-ethyl-l-methylpropyl and l-ethyl-2-methylpropyl; preferrably ethyl or methyl; ~ C3-Cg¢-haloalkyl and the haloalkyl moieties of C;-Cg-haloalkoxy: straight-chain or branched alkyl groups having 1 to 6 carbon atoms (as mentioned above), where the hydrogen atoms in these groups may be partially or fully replaced by halogen atoms as mentioned above, for example C;-C;-haloalkyl, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, l-chloroethyl, l-bromoethyl, l-fluorocethyl, 2-fluorocethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, . 25 2,2,2-trichloroethyl and pentafluoroethyl; preferrably 2,2,2-tri- fluoroethyl or 1,1,1l-trifluoroprop-2-yl; - C3-Cg~-cycloalkyl: monocyclic, saturated hydrocarbon radicals having 3 to 6 or 8 carbon ring members, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, preferably 5 to 7 carbon atoms, in particular cyclopentyl being optionally substituted by one or more halogen atoms, nitro, cyano, Cj;-Cg—alkyl or C;-Cg-alkoxy. - Cy-Cy—alkenyl: unsaturated, straight-chain or branched hydrocarbon radicals having 2 to 4 carbon atoms and a double bond in any position, for example ethenyl, l-propenyl, 2-propenyl, l-methylethenyl, 1l-butenyl, 2-butenyl, 3-butenyl, l-methyl-l-propenyl, 2-methyl-l-propenyl, l-methyl-2-propenyl and 40 2-methyl-2-propenyl; preferrably allyl or 2-methylallyl. - Cy-C4-haloalkenyl and the haloalkenyl moieties of : C;~C4-haloalkenyloxy: unsaturated, straight-chain or branched hydrocarbon radicals having 2 to 4 carbon atoms and a double bond 45 in any position (as mentioned above), where the hydrogen atoms in these groups may be partially or fully replaced by halogen atoms as mentioned above, in particular by fluorine, chlorine and bromine; - Cy-Cy-alkynyl: straight-chain or branched hydrocarbon radicals . 5 having 3 to 4 carbon atoms and a triple bond in any position, for example ethynyl, 1l-propynyl, 2-propynyl, l-butynyl, 2-butynyl, 1 3-butynyl and l-methyl-2-propynyl; ~ C3-Cs-haloalkynyl and the haloalkynyl moieties of

C,-Cy4-haloalkynyloxy: unsaturated, straight-chain or branched . hydrocarbon radicals having 2 to 4 carbon atoms and a triple bond in any position (as mentioned above), where the hydrogen atoms in these groups may be partially or fully replaced by halogen atoms as mentioned above, in particular by fluorine, chlorine and bromine;

S-membered heteroaryl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom: 5-mem- bered heteroaryl groups which, in addition to carbon atoms, may contain one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom as ring members, for example 2-fu- ryl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, 4-iso- thiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,2,4-thiadiazol-3-y1, 1,2,4-thiadi- azol-5-yl, 1,2,4-triazol-3-yl, 1,3,4-oxadiazol-2-y1l, 1,3,4-thia- diazol-2-~yl and 1,3,4-triazol-2-yl; 6-membered heteroaryl, containing one to four nitrogen atoms: 6-membered heteroaryl groups which, in addition to carbon atoms, may contain one to three or one to four nitrogen atoms as ring members, for example 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-py- ridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimi- dinyl, 2-pyrazinyl, 1,3,5-triazin-2-yl and 1,2,4-triazin-3-yl; preferred hetaryl moieties are pyridyl, pyrimidyl, pyrazolyl or thienyl. ” 40 5- or 6-membered heterocyclyl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom, for example 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-te- h trahydrothienyl, 3-tetrahydrothienyl, 2-pyrrolidinyl, 3-pyrroli- dinyl, 3-isoxazolidinyl, 4-isoxazolidinyl, 5-isoxazolidinyl, 45 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 3-py- razolidinyl, 4-pyrazolidinyl, 5-pyrazolidinyl, 2-oxazolidinyl, 4-oxazolidinyl, 5-oxazolidinyl, 2-thiazolidinyl, 4-thiazolidinyl,

S-thiazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1,2,4-oxa- diazolidin-3-yl, 1,2,4-oxadiazolidin-5-yl, 1,2,4-thiadiazoli- din-3-yl, 1,2,4-thiadiazolidin-5-y1, 1,2,4-triazolidin-3-y1, 1,3,4-oxadiazolidin-2-yl, 1,3,4-thiadiazolidin-2-yl, 1,3,4-tria- ; 5 zolidin-2-yl, 2,3-dihydrofur-2-yl, 2,3-dihydrofur-3-yl, 2,4-dihy- drofur-2-yl, 2,4-dihydrofur-3-yl, 2,3-dihydrothien-2-yl, 2,3-di- hydrothien-3-yl, 2,4-dihydrothien-2-yl, 2,4-dihydrothien-3-yl, ’ 2-pyrrolin-2-yl, 2-pyrrolin-3-yl, 3-pyrrolin-2-yl, 3-pyrro- lin-3-yl, 2-isoxazolin-3-yl, 3-isoxazolin-3-yl, 4-isoxazo- lin-3-yl, 2-isoxazolin-4-yl, 3-isoxazolin-4-yl, 4-isoxazo- lin-4-yl, 2-isoxazolin-5-yl, 3-isoxazolin-5-yl, 4-isoxazo- lin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4-isothiazo- lin-3-yl, 2-isothiazolin-4-yl, 3-isothiazolin-4-yl, 4-isothiazo- lin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazo- lin-5-yl, 2,3-dihydropyrazol-l-yl, 2,3-dihydropyrazol-2-yl, 2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl, 2,3-dihydropy- razol-5-yl1, 3,4-dihydropyrazol-1l-yl, 3,4-dihydropyrazol-3-yl, 3,4-dihydropyrazol-4-yl, 3,4-dihydropyrazol-5-yl, 4,5-dihydropy- razol-l-yl, 4,5-dihydropyrazol-3-yl, 4,5-dihydropyrazol-4-yl, 4,5-dihydropyrazol-5-yl, 2,3-dihydrooxazol-2-yl, 2,3-dihydrooxa- zol-3-yl, 2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl, 3,4-di- hydrooxazol-2-yl, 3,4-dihydrooxazol-3-yl, 3,4-dihydrooxazol-4-yl, 3,4-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxa- zol-3-yl, 3,4-dihydrooxazol-4-yl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1,3-dioxan-5-~yl, 2-tetrahydropyranyl, 4-tetrahy- dropyranyl, 2-tetrahydrothienyl, 3-hexahydropyridazinyl, 4-hexa- hydropyridazinyl, 2-hexahydropyrimidinyl, 4-hexahydropyrimidinyl,

S5-hexahydropyrimidinyl, 2-piperazinyl, 1,3,5-hexahydro-tria- zin-2~yl and 1,2,4-hexahydrotriazin-3-yl; preferred heterocyclyl groups are pyrrolidinyl, pyrazolidinyl, piperidinyl, piperazinyl or morpholin-4-yl.

The particularly preferred embodiments of the intermediates with respect to the variables correspond to those of the radicals RI,

R2, R3 and R% of formula I.

With respect to their intended use, preference is given to pyrimidines of formula I having the following substituents, where the preference is valid in each case on its own or in combina- , 40 tion:

Compounds of formula I are preferred wherein R! denotes C3-Cjig-al- * kyl, C3-Cg-cycloalkyl, C3-Cg-cycloalkyl-C;-Cg-alkyl, C;-Cip-haloal- kyl or phenyl being optionally substiuted by one to three halogen 45 atoms or C;-Cj;g-alkyl or C;-C;p-alkoxy.

Furthermore, particular preference is given to compounds I in which R! is C;-C;g_haloalkyl, preferably polyfluorinated alkyl, in particular 2,2,2-trifluoroethyl, 2-(1,1,1-trifluocropropyl) or 2-(1,1,1-trifluorobutyl). < 5 ’

Likewise, particular preference is given to compounds I in which

Rl denotes optionally substituted C3~Cg-cycloalkyl, preferably ! cyclopentyl or cyclohexyl. - 10 Moreover, particular preference is given to compounds I in which

R?2 represents phenyl being substituted by 2 or 3 substituents.

Most preferred at least one of these substituents is attached in the 2-position with respect to the point of attachment to the pyrimidine moiety. Such substituents preferably include halogen or alkoxy.

Furthermore, particular preference is given to compounds I in which R? represents a phenyl group of formula 1.2 1 1,3 i 4 wherein Ll! through L%4 each independently represent hydrogen, fluo- rine, chlorine or methoxy, in particular L! represents fluorine or chlorine, L2 and 1% each independently represent hydrogen, fluorine or chlorine, and L3 represents hydrogen, fluorine, chlo- rine or methoxy.

Particular preference is given to compounds of formula I in which

R3 is chlorine.

Besides, particular preference is given to compounds I in which R4 represents hydrogen, C;-Cg-alkyl, Cy-Cs-alkenyl or C,-Cg-alkynyl; or phenyl-C;-Cs-alkyl, wherein the phenyl ring may be substituted by one or two halogen atoms.

Likewise, particular preference is given to compounds I in which : 40 R? is hydrogen, C;-Cg-alkyl or benzyl, especially C;-Cg¢-alkyl.

Particular preference is given to compounds I in which X is NR3 : and R> is hydrogen, C;-Cjp-alkyl or C;-Cjg-haloalkyl, in particular hydrogen. 45

Besides, particular preference is given to compounds I in which R> represents. C;-Cg¢~alkyl, especially hydrogen or methyl.

Particular preference is also given to compounds I in which X re- present NR and R! together with the interjacent nitrogen atom form an optionally substituted heterocyclic ring, preferably an optionally substituted 3- to 7-membered heterocyclic ring, in : 5 particular a pyrrolidine, piperidine, tetrahydropyridine, in par- ticular 1,2,3,6-tetrahydropyridine or azepane ring which is op- tionally substituted by one or more C;-Cip~alkyl groups.

Most preferred are the compounds of formula IA

RS }

Rr.

Noon

RY N— \ 13 IA

NWA

N

3 4 in which R! to R>® have the meaning given in formula I, L! is F or

Cl, L2 and L* each independently are H, F or Cl, and L3 is H, F,

Cl or OCH;.

Likewise, most preferred are the compounds wherein R3 is chlorine,

X is NH, R* is C;-Cg-alkyl,Cy-Cg-alkenyl or C;-Cg-alkynyl, espe- cially C;-Cg-alkyl, R2 represents phenyl optionally substituted by one or more fluorine and/or chlorine atoms and/or methoxy groups.

Particularly preferred are following compounds of formula IA:

I ES EE A EA ca(cayCcry | om Jct | cH [EF JEFF

CEA CES I a 0 cmH [| oo Jer] ca [FEF |F (OF CA (CH) (GE:

EAP TGAIGHE

Gi {cry CF

Included in the scope of the present Invention are (R) and (S) . 40 isomers of compounds of general formula I having a chiral center and the racemates thereof, and salts, N-Oxides and acid addition compounds.

The compounds according to formula I are superior through their 45 valuable fungicidal properties, in particular their enhanced sy- stemicity. For example, they can be used in agriculture or rela- ted fields for the control of phytopathogenic fungi such as

Alternaria solani, Botrytis cinerea, Cercospora beticola, Clados- porium herbarum, Corticium rolfsi, Erysiphe graminis,

Helminthosporium tritici repentis, Lepfosphaeria nodorum, Micro- nectriella nivalis, Monilinia fructigena, Mycosphaerella liguli- i S cola, Mycosphaerella pinodes, Rhizoctonia solani, Sclerotinia sclerotiorum, Uncinula necator and Venturia inaequalis, in parti- cular Pyricularia oryzae, Rhizoctonia solani and Venturia inaequalis. The compounds of formula I according to the invention possess a high fungicidal activity within a wide concentration range. -

Due to excellent activity, the cornpounds of formula I may be used in cultivation of all plants where infection by phyto- pathogenic fungi is not desired, e.g. cereals, solanaceous crops, vegetables, legumes, appies, vine.

The Invention further provides a fungicidal composition which comprises an active ingredient, which is at least one compound of formula I as defined above, and one or more carriers. A method of making such a composition is also provided which comprises brin- ging a compound of formula I as defined above into association with the carrier(s). Such a composition may contain a single ac- tive ingredient or a mixture of several active ingredients of the present Invention. lt is also envisaged that different isomers or mixtures of isomers may have different levels or spectra of acti- vity and thus compositions may comprise individual isomers or mixtures of isomers.

A composition according to the Invention preferably contains from 0.5% to 95% by weight (w/w) of active ingredient.

A carrier in a composition according to the Invention is any ma- terial with which the active ingredient is formulated to facili- tate application to the locus to be treated, which may for example be a plant, seed, soll, or watet in which a plant grows, or to facilitate storage, transport or handling. A carrier may be a solid or a liquid, including material which is normally a gas but which has been compressed to form a liquid. 40 The compositions may be manufactured into e.g. emulsion concen- ’ trates, solutions, oil in watet emulsions, wettable powders, so- luble powders, suspension concentrates, dusts, granules, watet ‘ dispersible granules, micro-capsules, gels, tablets and other formulation types by wellestablished procedures. These procedures 45 include intensive mixing and/or milling of the active ingredients with other substances, such as fillers, .solvents, solid carriers, surface active compounds (surfactants), and optionally solid and/

Claims (19)

Claims:

1. Pyrimidines of formula I RE ) X 2 R IY : : 4 R Xx on NT ORS ] 10 CN in which Rl represents hydrogen or Ci1-Cip-alkyl, C;-Cjig-haloalkyl, Cy-Cg-alkenyl, C,-Cg-alky- nyl, C4-Cg-alkadienyl, C;-Cigp-alkoxy, C3-Cg-cycloalkyl, phenyl, or 5- or 6-membered heteroaryl or 5- or 6-membered heterocy- clyl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom, or tri-C;-Cg-alkyl-silyl, formyl or C;-C;p-alkoxycarbonyl; wherein R! groups are unsubstituted or substituted by one to three groups Ra R2 halogen, nitro, cyano, hydroxy or C1-Cig-alkyl, C3-Cg-cycloalkyl, C3-Cg-cycloalkenyl, C1-Cig-haloalkyl, C3-Cg¢~halocycloalkyl, C;-Cigp-alkoxy, © C1=Cjp-haloalkoxy, C;-Cigp-haloalkoxy, C;-Cg-alkoxycar- bonyl, tri-C;-C4-alkylsilyl, phenyl, halo- or dihalo- phenyl or 5- or 6-membered heteroaryl, containing one to four nitrogen atoms or one to three nitrogen atoms and one sulfur or oxygen atom; RZ? represents phenyl, C3-Cg-cycloalkyl or 5- or 6-membered heteroaryl, containing one to four nitrogen atoms or one 40 to three nitrogen atoms and one sulfur or oxygen atom, - which are unsubstituted or substituted by one to three groups R2; R3 represents hydrogen, halogen or

AMENDED SHEET os WO 01/96314 PCT/EP01/06565 C,-C,o-alkyl, C,-C,-alkoxy, C,-Cyo-alkylthio, C;-C,,- ® alkylamino or di-C,-C,,-alkylamino; which are unsubstituted or substituted by one to three groups RZ; R* represents hydrogen or C,-Cyp-alkyl, C,-C,-alkenyl or C,-C.-alkynyl; which are unsubstituted or substituted by one to three groups R?; _ and X represents O, S, NR® or a single bond, wherein R® represents hydrogen or C,-C,,-alkyl; or R' and R® together with the interjacent nitrogen atom form a heterocyclic ring.

2. Pyrimidines of formula I according to claim 1, in which R? represents a phenyl group of formula

1.2 Li 1 # 4 wherein L' through L* each independently represent hydrogen, fluorine, chlorine or methoxy.

3. Pyrimidines of formula IA RS Rl NN I! 1.2 RY N— \ ( 13 IA aa 3 4 in which R' to R® have the meaning given in claim 1, and L! through L* are as defined in claim 2.

4. Pyrimidines according to any one of claims 1 to 3 in which R? represents chlorine. 40

5. Pyrimidines according to any one of claims 1 to 4 in which R* represents hydrogen, C,-C.-alkyl or benzyl.

6. A process for the preparation of pyrimidines of formula I ac- cording to claim 1 wherein R% is optionally substituted alkyl, alkenyl or alkynyl by treating compounds of the for- mula II > 1 » «R 2 —_ JA _ 10. . . _ . RE in which R! through R3 and X are as defined in formula I; with a base and an alkylation agent of formula III 4_ R%-Y III in which R¢ is C;-Cg-alkyl, Ci-Cg-alkenyl or C;-Cg-alkynyl; . which are unsubstituted or substituted by one to three groups Ra, and Y represents halogen atom.

7. A process for the preparation of pyrimidines of formula I ac- cording to claim 1 wherein R% is is C;-Cg-alkyl, C;-Cg-alkenyl or C1~Cg-alkynyl which are unsubstituted or substituted by one to three groups R2 by reacting sulfones of formula VI x ® 2 Qe vi FEN R? in which R! through R3 and X are as defined in formula I and ~~ R® is C;-Cg-alkyl or C;-Cg-haloalkyl; with alkylated cyanamides of formula VII 2 N Sy © VII in which R% is is C;-Cg-alkyl, C;-Cg-alkenyl or C;~Cg-alkynyl which are unsubstituted or substituted by one to three groups 40 R23; wherein sulfones of formula VI are obtained by reacting ’ 2-thiopyrimidinederivatives of formula VIII . «F R2 III 45 je v RS—5” NT OR’

AMENDED SHEET in which the variables are as defined in formula VI; with @ oxidizing agents.

8. Compounds of formulae VI and VIII as defined in claim 7.

9. A fungicidal composition which comprises a carrier and an ef- fective amount of at least one compound of formula I as def- ined in claim 1.

10. A method of combating fungus at a locus which comprises treating the locus with an effective amount of at least one compound of formula I as defined in claim 1.

11. Pyrimidines of formula I as claimed in any one of claims 1 to 5, substantially as hereinbefore described and exemplified.

12. Pyrimidines of formula I including any new and inventive integer or combination of integers, substantially as herein described.

13. A process according to the invention for preparing pyrimidines of formula I, substantially as hereinbefore described and exemplified.

14. A process for preparing pyrimidines of formula I including any new and inventive integer or combination of integers, substantially as herein described.

15. Compounds of formulae VI and VIII as claimed in claim 8, substantially as hereinbefore described and exemplified.

16. Compounds of formulae VI and VIII including any new and inventive integer or combination of integers, substantially as herein described.

17. A fungicidal composition as claimed in claim 9, substantially as hereinbefore described and exemplified. 40

18. A fungicidal composition including any new and inventive integer or combination of integers, substantially as herein described.

19. A method according to the invention for combating fungus at 45 a locus, substantially as hereinbefore described and exemplified.