LV10556B - A method of controlling or preventing an attack on cultivated plants by harmful insects or phytopathogenic microorganisms - Google Patents

Abstract

Utilization: in agriculture as possessing fungicide and insecticide activities.The summary of the invention consists in the fact of the preparation of derivatives 2-anilinpyrinidine of general formula:in which R1 and R2 - independently each other means hydrogen, halogen, C1-C3 alkyl, C1 - C2 halogenalkyl, C1 - C3 - alkoxy or C1 - C3 -halogenalkoxy; R3 - hydrogen, C1-C4 alkyl or substituted by halogen or hydroxygroup C1-C4 alkyl, cyclopropyl or substituted, by methyl, cyclopropyl; R4 - C3-C6 cycloalkyl or substituted equal or differently by methyl and/or halogen up to triplet (C3-C6) cycloalkyl. Reagent I: salt of phenylguanidin of the formulain which A- - anion of mineral or guanidin with formulaReagentII: diketone: R3C(O)CH2C(OR); cyclization is leaded at temperature 60-160°C.

Description

LV 10556

A METHOD OF CONTROLLING OR PREVENTLNG ATs ATTACK ON

CULTIVATED PLANTS

BY HARMFUL LNSECTS OR PHVTOPATHOGENIC MICROORGANISMS

The present invention relates to novel 2-anilinopyrimidine derivatives of formula I below. It relates also to the preparation of those substances and to agrochemical compositions that contain as active ingredient at least one of those compounds. The invention relates also to the prepara-tion of the mentioned compositions and to the use of the active ingredi-ents or of the compositions for controlling pests, especially harmful insects and plant-destructive microorganisms, preferablv fungi.

The compounds according to the invention correspond to the general formula I

(I) in which:

Ri and R2 independently of one another are hydrogen, halogen, Ci-C]alkyl, Ci-Cihaloalkvl, Ci-C3alkoxy or

Ci-C3haloalkoxy; R.3 13 hydrogen; Ci-Ci,alkyl; or Cj-C^alkvl substituted by halogen, hydroxy and/or cyano; cyclopropyl; or cyclopropyl mono- to tri-substituted by methyl and/or by halogen; and Ri» is C3-C6cycloalkyl or C3~Cocycloalkyl mono-to tri-substituted by methyl and/or by halogen; including their acid addition salts and mētai salt complexes.

Depending on the number of carbon atoms indicatēd, alkyl by itself or as a component of another substituent, such as haloalkyl, alkoxy or halo-alkoxy, is to be understood as meaning, for example, methyl, ethyl, propyl, butyl and their isomers, such as, for exaraple, isopropyl, iso-butyl, tert.-butyl or sec.-butyl. Halogen, also called Hal, is fluorine, chlorine, bromine or iodine. Haloalkyl and haloalkoxy are mono- to per-halogenated radicals, such as, for example, CHCl;, CH2F, CClj, CH^Cl, 2 CHF2, CF3, CHzCHzBr, C2C15, CH2Br, CHBrCl etc., preferably CF3. Depending on the number of carbon atoms indicated, cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. N-pyrimidinylaniline compounds are already known. For example, in published European Patent Application 0 224 339 and in GDR Patent Spec-ification 151 404, compounds that have an N-2-pyrimidinyl structure are described as being effective against plant-destructive fungi. However, the known compounds have hitherto been unable fully to meet the demands made of them in practice. The characteristic difference betveen the compounds of formula I according to the invention and the known compounds is that at least one cycloalkyl radical and other substituents have been introduced into the anilinopyrimidine structure, as a result of vhich an unexpectedly high fungicidal activitv and insecticidal action is obtained with the novel compounds.

The compounds of formula I are oils, resins or solids that are stable at room temperature and that are distinguished by valuable microbicidal properties. They can be used preventively and curatively in the agricul-tural sector or related fields for controlling plant-destructive micro-organisms. The compounds of formula I according to the invention are distinguished at low application concentrations not only by excellent insecticidal and fungicidal action but also by the fact that they are especiallv veli tolerated by plants.

The invention relates both to the free compounds of formula I and to their addition salts with inorganic and organic acids and to their com-plexes with mētai salts.

Salts according to the invention are especially addition salts with acceptable inorganic or organic acids, for example hydrohalic acids, for example hydrochloric, hydrobromic or hydriodic acid, sulfuric acid, phos-phoric acid, phosphorous acid, nitric acid, or organic acids, such as acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, glycolic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid, oxalic acid, formic acid, benzenesulfonic - 3 - LV 10556 acid, p-toluenesulfonic acid, methanesulfonic acid, salicylic acid, p-aminosalicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid or 1,2-naphthalenedisulfonic acid. Mētai salt complexes of formula I consist of the organic molecule on which they are based and an inorganic or organic mētai salt, for example the halides, nitrates, sulfates, phosphates, acetates, trifluoroacetates, trichloroacetates, propionates, tartrates, sulfonates, salicylates, benzoates etc. of the elements of the second main group, such as calcium and magnesium, and of the third and fourth main groups, such as alumi-nium, tin or lead, and of the first to eighth subgroups, such as chromium, manganese, iron, cobalt, nickel, copper, zinc etc. The sub-group elements of the fourth period are preferred. The metāls can be in any of their various valencies. The mētai complexes can be raono- or poly-nuclear, that is to say they can contain one or more organic molecu-lar moieties as ligands.

An important group of phytofungicides and insecticides is formed by those of formula I in which Ri and R* are hydrogen. A special group is formed by the following compounds of formula I in which:

Ri and Rs independently of one another are hydrogen, halogen, Ci-Cjalkyl, Ci-C2haloalkyl, Cj,-Cjalkoxy or

Ci-Cjhaloalkoxy; Rj is hydrogen, Ci-Ci,alkyl or Ci-Ci»alkyl substituted by halogen or by cyano; and Ri, is C3-C6cycloalkyl or Cj-Cecycloalkyl substituted by methyl or by halogen.

The folloving groups of active ingredients are preferred becauee of their pronounced microbicidal, especially phytofungicidal, activity:

Group la: Compounds of formula I in which:

Ri and Rj independently of one another are hydrogen, fluorine, chlorine, bromine, methyl, ethyl, halomethyl, methoxy, ethoxy or halomethoxy; R3 is hydrogen, methyl, methyl substituted by fluorine, chlorine, bromine or by 4 cyano; ethyl, ethyl substituted by fluorine, chlorine, bromine or by cyano; n-propyl or sec.-butyl; and Ri, is C3-Cccycloalkyl or C3-C0cyclo-alkyl substituted by raethyl, fluorine, chlorine or by bromine.

Of the above-mentioned compounds, an especially preferred group is formed by those in which R3 = R3 hydrogen (= Group laa).

Group lb; Compounds of formula I in which:

Ri and R2 independently of one another are hydrogen, chlorine, bromine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or difluoromethoxy; R3 is hydrogen, methyl, methyl substituted by fluorine, chlorine or by cyano, ethyl or n-propyl; and Ru is C3-Cscycloalkyl or C3-Cscycloalkyl substituted by methyl or by chlorine.

Of the above-mentioned compounds, an especially preferred group is formed by those in which Ri = R: = hydrogen (= Group lbb).

Group Ic: Compounds of formula I in which:

Ri and Rj independently of one another are hydrogen, chlorine, methyl, methoxy, ethoxy or trifluoromethyl; R3 is hydrogen, methyl, ethyl or trifluoromethyl; and Ri, is cyclopropyl or cyclopropyl substituted by raethyl or by chlorine.

Of the above-mentioned compounds, an especially preferred group is formed by those in which Ri R3 = hydrogen (= Group lcc) .

Group ld: Compounds of formula I in which:

Ri is hydrogen; R2 and R3 independently of one another are hydrogen or methyl; and Ri, is cyclopropyl or cyclopropyl substituted by methyl. - 5 - LV 10556

Group 2a: Compounds of formula I in which:

Ri and R2 independently of one another are hydrogen, halogen, Ci-C2alkyl, halomethyl, Ci-C2alkoxy or Ci~C2haloalkoxy; R3 1s hydrogen; Ci-Ciialkyl; Cj-C2alkyl substituted by halogen or by hydroxy; cyclopropyl; or cyclo-propyl mono- to tri-substltuted by methyl and/or by halogen; and R<» is C3-C6cycloalkyl or C3-Ci,cycloalkyl mono- to tri-substituted by methyl and/or by halogen.

Of the above-mentioned compounds, an especially preferred group 1s formed by those in which Ri * R* “ hydrogen (« Group 2aa).

Group 2b: Compounds of formula I in which:

Ri and R» independently of one another are hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, methoxy or difluoromethoxy; R3 is hydrogen; Ci~C3alkyl; Ci-C2alkyl substituted by halogen or by hydroxy; cyclopropyl; or cyclopropyl mono- to tri-substituted by methyl and/or by halogen; and Ri* is C3-Cccycloalkyl or Cj-Ci,cycloalkyl mono- to tri-substituted by methyl and/or by halogen.

Of the above-mentioned compounds, an especially preferred group is formed by those in which Ri “ Rz *= hydrogen (= Group 2bb).

Group 2c: Compounds of formula I in which:

Rj and R2 independently of one another are hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy or difluoromethoxy; R3 is hydrogen; Ci-C3alkyl; Cx-Caalkyl substituted by halogen or by hydroxy; cyclopropyl; or cyclopropyl mono- to tri-substituted by methyl and/or by halogen; and Rh is C3-C6cycloalkyl or C3-Ci»cycloalkyl mono-to tri-substituted by methyl and/or by halogen.

Of the above-mentioned compounds, an especially preferred group is formed by those in which Rx R2 hydrogen (= Group 2cc). 6

Group 2d: Compounds of formula I in which:

Ri and R2 are hydrogen; R] is'Ci-C;jalkyl; methyl substituted by fluorine, chlorine, bromine or by hydroxy; cyclopropyl; or cyclopropyl substituted by roethyl, fluorine, chlorine or by bromine; and Ri, is Cj-Ci,cycloalkyl or Cj-Ci,cycloalkyl mono- to tri-substituted by methyl and/or by fluorine, chlorine or by bromine.

Of the individual substances that are especially preferred there may be mentioned, for example: 2-phenylamino-4-methyl-6-cyclopropylpyrimidine (comp. no. 1.1); 2-phenylamino-4-ethyl-6-cyclopropylpyrimidine (comp. no. 1.6); 2-phenylamino-4-methyl-6-(2-methylcyclopropyl)-pyrimidine (comp. no. 1.14); 2-phenylamino-4,6-bis(cyclopropyl)pyrimidine (comp. no. 1.236); 2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimidine (comp. no. 1.48); 2-phenylamino-4-fluoromethyl-6-cyclopropylpyrimidine (comp. no. 1.59); 2-phe ny 1amino-4-hydroxymethy1-6-(2-methylcyclopropyl)-pyrimidine (comp. no. 1.13); 2-phenylamino-4-methy1-6-(2-fluorocyclopropyl)-pyrimidine (comp. no. 1.66); 2-phenylamino-4-methy1-6-(2-chlorocyclopropyl)-pyrimidine (comp. no. 1.69); 2-phenylaraino-4-methyl-6-(2-difluorocyclopropyl)-pyrimidine (comp. no. 1.84); 2-phenylamino-4-fluoromethy1-6-(2-fluorocyclopropyl)-pyrimidine (comp. no. 1.87); 2-phenylamino-4-fluoromethy1-6-(2-chlorocyclopropyl)-pyrimidine (comp. no. 1.94); 2—phenylamino-4—fluoromethy1-6-(2-methylcyclopropy1)-pyrimidine (comp. no. 1.108); 2-phenylamino-4-ethy1-6-(2-raethylcyclopropyl)-pyrimidine (comp. no. 1.131); 2-(p-fluorophenylamino)-4-methyl-6-cyclopropylpyrimidine (comp. no. 1.33). - 7 -LV 10556

The compounds of formula I are prepared as follovs: 1. a phenylguanidine salt of formula Ila Ri. Θ Θ (Ha) V~\ _/Hi •f* nh2 or the free guanidine base of formula Ilb Rly-\ /« (Ilb)

X NH2 (III) is reacted with a diketone of formula III R j—2—CHj—^—R„

vithout solvents or in an aprotic solvent, preferably in a protic solvent, at temperatures of from 60°C to 160eC, preferably from 6Q°C to 110°C; or 2. In a multi-stage process: 2.1 urea of formula IV o=c

(IV)

1s reacted with a diketone of formula III R3 4

:—CHZ

(III)

in the presence of an acid in an inert solvent at temperatures of from 20°C to 140°C, preferably from 20°C to 40eC, and is cyclised to give a pyrimidine compound of formula V - 8 ΗΟ—·

V Ν= / \ / »

Rj (ν) and 2.2 the QH group in the resulting compound of formula V is exchanged for halogen by further reaction with excess P0Hal3, in the presence or in the absence of a solvent, at temperatures of from 50°C to 110°C, preferably at the reflux temperature of POHal3, to yield

Hal— (VI)

Hal in the above formulae being halogen, especially chlorine or bromine, and

2.3 the resulting compound of formula VI is reacted further with an aniline compound of formula VII

Ri H2N—

/"V (VII)

Rs depending on the reaction conditions either a) in the presence of a proton acceptor, such as an excess of the aniline compound of formula VII or an inorganic base, with or without solvents, or b) in the presence of an acid in an inert solvent, in each case at temperatures of from 60°C to 120°C, preferably from 80°C to 100°C; or 9LV 10556 3. in a two-stage process:

3.1 a guanidine salt of formula VIII

©

A Θ (VIII)

is cyclised with a diketone of formula III

Ra-

CIII) a) vithout solvents at temperatures of from 100°C to 160°C, preferably from 120eC to 150eC, or b) in an inert solvent at temperatures of from 30°C to 140°C, preferably from 60°C to 120°C,

to give a pyrimidine compound of formula IX

(ix)

and 3.2 the resulting compound of formula IX is reacted with a compound of formula X

(X) in the presence of a proton acceptor in aprotic solvents at temperatures of from 30®C to 140eC, preferably from 60°C to 120®C, to remove HY, the substituents Ri to Ri, in formulae II to X being as defined for formula I, being an acld anion and Y being halogen; or - 10 - 4. in a multi-stage process:

4.1a) thiourea of formula XI • NH2 S»(/ (XI) nh2

is reacted with a diketone of formula III (III)

Rj—č—CH2—č—Ri* in the presence of an acid in an inert solvent at temperatures of from 20°C to 140°C, preferably from 20°C to 60°C, and cyclised to give a pyrimidine compound of formula HS— N—· \

Ri (XII) R.,

and the alkali mētai or alkaline earth mētai salt thereof is reacted with a compound of formula XIII

ZRS (XIII),

wherein Rs is Ci-Coalkyl, or benzyl that is unsubstituted or substituted by halogen and/or by Ci~Cualkyl and Z is halogen, to give a pyrimidine compound of formula XIV R5S-

N=

(XIV)

Nu

or b) an isothiuronium salt of formula XV Η2ΝχHz^ C-SRs ΑΘ (XV) LV 10556 - n - is reacted vith a diketone of formula III, preferably in a protic solvent, at temperatures of from 20°C to 140°C, preferably from 20°C to 80°C, and a pyrimidine compound of-fonDuTa XIV is likevise obtained, and

4.2 the resulting compound of formula XIV is oxidised vith an oxidising aģent, for example with a peracid, to give the pyrimidine compound of formula XVI

RsS02

^R·» (XVI) and

4.3 the resulting compound of formula XVI is reacted vith a formylaniline of formula XVII

Ri V\/X-/

-NHCHO (XVII)

in an inert solvent in the presence of a base as proton acceptor, at temperatures of from -30eC to 120eC, to give a compound of formula XVIII

(XVIII) and 4.4 the resulting compound of formula XVIII is subjected to hydrolysis in the presence of a base, for example an alkali mētai hydroxide, or of an acid, for example a hydrohalic acid or sulfurlc acid, in vater or aqueous solvent mixtures, such as aqueous alcohols or dimethylformamlde, at temperatures of from 10°C to 110°C, preferably from 30°C to 60°C, the substituents Ri to Ri, in formulae XI to XVIII being as defined for 0 formula I and A being an acid anion and Y being halogen. 12

Compounds of formula I in which R3 is the CHzOH group can be prepared by special processes, as follovs: AI.1 the guanidine salt of formula Ila

—NH- m 2 Θ (Ila) or the guanidine of formula Ilb

—NH- \

NH NH (Ilb) 2

is reacted with a ketone of formula XIX (RcO)2CH-C-CH2-C-Rm (XIX)

in which R& is Ci-Citalkyl, in a protic solvent or vithout solvents, at temperatures of from 40°C to 160°C, preferably from 60°C to 110°C, to give a pyrimidine compound of formula XX

R y-\ /- /CH(OR6)2 (XX) /

and

AI.2 the resulting acetal of formula XX is hydrolysed in the presence of an acid, for example a hydrohalic acid or sulfuric acid, in water or aqueous solvent mixtures, for exaraple with solvents such as alcohols or dimethylformamide, at temperatures of from 20°C to 100°C, preferably from 30°C to 60°C, to give the pyrimidinealdehyde of formula XXI

-NH— \=· ycno (XXI) \ /

Nu and LV 10556 - 13 -

Al.3 the resulting compound of formula XXI is hydrogenated vith elemental hydrogen using a catalyst or ie reduced vith a reducing aģent, such as aodium borohydride, to give the corresponding alcohol XXII

^CHaOH ^ \ (XXII); N=· R2 Rm or

A2.1 the guanidine salt of formula Ila or the guanidine of formula Ilb is reacted vith a diketone of formula XXIII R7OCH2

(XXIII)

in vhich R7 is benzyl that is unsubstituted or substituted by halogen or by Ci-Ci,alkyl, in a protic solvent or vithout solvents, at temperatures of from 40°C to 160°C, preferably frora 60°C to 110°C, to give a pyrimidine compound of formula XXIV

-NH-· N= CH2OR7

« V (XXIV)

Rm and in that compound A2.2 the CH2OR7 radical-is converted into a CH2OH radical by hydrogena-tion in a solvent, preferably an aprotic solvent, for example dioxane or tetrahydrofuran, vith a catalyst, such as palladium-on-carbon, preferably Raney nickel, at temperatures of from 20eC to 90°C, preferably from 50eC to 90eC; or

A3.1 the guanidine salt of formula Ila or the guanidine of formula Ilb is reacted vith a diketone of formula XXV R8OCH2

(XXV) 14

in which R8 is Cl-C6alkyl, C3-CGalkenyl or benzyl that is uasub3tituted or 3ubstituted by halogen or by Ci-C<,alkyl, in a protic solvent or without solvents, at temperatures of from 40°C to 160eC, preferably from 60°C to 110°C, to give a pyrimidine compound XXVI 14

,CH2ORc (XXVI) and A3.2 with the resulting compound of formula XXVI an ether cleavage is carried out with a hydrohalic acid, preferably hydrobromic acid, or a Lewis acid, such as aluminium halide (for example AICI3) or boron halide B(Hal)3 (for example BBrj or BCI3), in aprotic solvents, for example hydrocarbons or halogenated hydrocarbons, at temperatures of from -80°C to 30°C, preferably from -70°C to 20eC.

Compounds of formula I in vhich R: is the CHjHal group can be prepared by reacting a compound of formula XXII with phosphorus halide or thionyl halide in the presence of tertiary bases, for example pyridine or triethylamine, in inert solvents, at temperatures of from 0°C to 110°C, preferably from 0°C to 80°C.

Compounds of formula I in which R3 is the CH2F group can be prepared by reacting a compound of formula XXVII

,CH2X (XXVII) in which X is chlorine or bromine, with potassium fluoride, preferably lyophilised potassium fluoride, in the presence of catalytic amounts of cesiura fluoride or a Crown ether, for example 18-Crown-6-ether, in aprotic solvents, such as acetonitrile, at temperatures of from 50eC to 160eC in a pressure autoclave. - 15 - LV 10556 A further process for the preparation of compounds of formula I in which R3 is the CH2F group consists in fluorinating a compound of formula XXII with N,N-diethylaminosulfur trifluoride ( DAST) in aprotic solvents, such as dichloromethane, chloroform, tetrahydrofuran or dioxane, at temperatures of from 0°C to 1Q0°C, preferably froro 10°C to 50eC.

In the above formulae XVIII to XXVII too, Ri, R2 and Ri» are as defined for formula I.

In the described processes, in compounds of formulae Ila and VIII the folloving salt radicals, for example, are suitable for the acid anion A^: carbonate, hydrogen carbonate, nitrate, halide, sulfate and hydrogen sulfate.

In the processes described above, in the compound of formula XV the Θ following salts, for example, are suitable for the acid anion A : halide, sulfate and hydrogen sulfate.

Halide in each case is to be understood as meaning fluoride, chloride, bromide or iodide, preferably bromide or chloride.

The acids used are especially inorganic acids, such as, for example, hydrohalic acids, for example hydrofluoric acid, hydrochloric acid or hydrobromic acid, and also sulfuric acid, phosphoric acid or nitric acid; hovever, suitable organic acids may also be used, such as, inter alia, acetic acid and toluenesulfonic acid.

As proton ačceptors there are used, for example, inorganic or organic bases, such as, for example, alkali mētai or alkaline earth mētai compounds, for example the hydroxides, oxides or carbonates of lithium, sodium, potassium, magnesium, calcium, strontium and barium, or also hydrides, such as, for example, sodium hydride. As organic bases there may be mentioned, for example, tertiary amines, such as triethylamine, triethylenediamine, pyridine.

In the processes described above, for example, the following solvents may be used, dependent on the particular reaction conditions, in addition to those already mentioned: 16

Halogenated hydrocarbons, especially chlorinated hydrocarbons, such as tetrachloroethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, chloronaphthalene, carbon tetra-chloride, trichloroethane, trichloroethylene, pentachloroethane, di-fluorobenzene, 1,2-dichloroethane, 1,1-dichloroethane, 1,2-cis-dichloro-ethylene, chlorobenzene, fluorobenzene, brotnobenzene, dichlorobenzene, dibromobenzene, chlorotoluene, trichlorotoluene; ethers, 3uch as ethyl propyl ether, methyl tert.-butyl ether, n-butyl ethyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, diisopropyl ether, anisole, cyclohexyl methyl ether, diethyl ether, ethylene glycol diraethyl ether, tetrahydrofuran, dioxane, thioanisole, dichlorodiethyl ether; nitrohydro carbons, such as nitromethane, nitroethane, nitrobenzene, chloronitro-benzene, o-nitrotoluene; nitriles, such as acetonitrile, butyronitrile, isobutvronitrile, benzonitrile, m-chlorobenzonitrile; aliphatic or cyclo aliphatic hydrocarbons, such as heptane, hexane, octane, nonane, cymol, Petroleum fractions within a boiling point range of from 70°C to 190°C, cyclohexane, methylcyclohexane, decalin, petroleum ether, ligroin, tri-methylpentane, such as 2,3,3-trimethylpentane; esters, such as ethyl acetate, ethyl acetoacetate, lsobutyl acetate; amides, for example formamide, methylformami.de, dime thyl f ortnamide ; ketones, such as acetone, methyl ethyl ketone; alcohols, especially lower aliphatic alcohols, such as, for example, methanol, ethanol, n—propanol, isopropanol and the butanol isomers; and, where appropriate, also water. Also suitable are mixtures of the mentioned solvents and diluents.

Methods of synthesis that are analogous to the above-described prepara-tion processes have been published in the literature.

As references there may be mentioned:

Process 1: A, Kreutzberger and J, Gillessen, J. Heterocyclic Chem. 22, 101 (1985).

Process 2:, Stage 2.1; 0. Stark, Ber. Dtsch. Chem. Ges. 42, 699 (1909); J. Hale, J. Am. Chem. Soc. 36, 104 (1914); G.M. Kosolapoff, J. Org.

Chem. 26, 1895 (1961). Stage 2.2: St. Angerstein, Ber. Dtsch. Chem.

Ges. 34, 3956 (1901); G.M. Kosolapoff, j. org. Chem. 26, 1895 (1961). LV 10556 - 17 -

Stage 2.3: M.P.V. Boarland and J.F.W. McOmie, J. Chem. Soc. 1951, 1218; T. Matsukava and K. Shirakuva, J. Phacra. Soc. Japan 2i» 933 (1951); Chem. Abstr. 46, 4549 (1952).

Process 3: A. Combes and C. Combes, Buli. Soc. Chem. (3), 7, 791 (1892); W.J. Hale and F.C. Vibrans, J. Am. Chem. Soc. 40, 1046 (1918).

The described preparation processes, including ali partial steps, form part of the present inventlon.

The folloving compounds, vhich are used as intermediates in the preparation of the compounds of formula I, are novel and form part of the present inventlon: 1) Compounds of formula /N- - R -o N=· in which:

Rq ie halogen or R5SO2; R3 is hydrogen; Ci~Ci,alkyl; or Cļ-Ci,alkyl substituted by halogen, hydroxy and/or cyano; cyclopropyl; or cyclopropyl mono- to tri-substituted by methyl and/or by halogen; Ri» is C3-Cocycloalkyl or C3-Cocycloalkyl mono- to tri-substituted by methyl and/or by halogen; and R5 is Ci-Caalkyl or benzyl that is unsubstituted or substituted by halogen and/or by Ci-Ct,alkyl. Chlorine and bromine are preferred as halogen substituent R .

2) Compounds of formula XXI

-NH— /

,CHO (xxi)

Rm in vhich:

Ri and R2 independently of one another are hydrogen, halogen, Ci-C3alkyl, Ci-C2haloalkyl, Ci~C3alkoxy or 18 Cχ~C3haloalkoxy; and Ri, is C3~Cccycloalkyl or Cj-Cccycloalkyl mono~ to tri-substituted by methyl and/or by halogen.

Surprisingly, it has been found that the compounds of formula I have, for practical field application purposes, a very advantageous biocidal spectrum against insects and phytopathogenic microorganisms, especially fungi. Compounds of formula I have very advantageous curative, preventive and, in particular, systemic properties, and can be used for protecting numerous cultivated plants. With the compounds of formula I it is possible to inhibit or destroy the pests which occur in plants or in parts of plants (fruit, blossoms, leaves, steros, tubers, roots) in different crops of useful plants, vhile at the same time the parts of plants vhich grow later are also protected, for example, from attack by phytopathogenic microorganisms.

The compounds of formula I are effective, for example, against the phytopathogenic fungi belonging to the folloving classes: Fungi imperfecti (especially Botrytis, and also Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria); Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia). They are also effective against the class of the Ascomycetes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and of the Oomycetes (e.g. Phytophthora, Pythium, Plasmopara). The comounds of formula I can also be used as dressing aģents for protecting seeds (fruit, tubers, grains) and plant cuttings against fungus infections as veli as against phytopathogenic fungi vhich occur in the soil. In addition, compounds of formula I are effective against insect pests, for example against pests on cereals such as rice.

The invention also relates to compositions containing as active ingredient compounds of formula I, especially plant-protecting compositions, and to their use in the agricultural sector or related fields.

The present invention further embraces the preparation of those compositions, vhich comprises homogeneously mixing the active ingredient vith one or more compounds or groups of compounds described herein. The invention furthermore relates to a method of treating plants, vhich comprises applying thereto the novel compounds of formula I or the novel compositions . - 19 - LV 10556

Target crops to be protected within the scope of the present invention comprise e.g. the folloving species of plants: cereals (wheat, barley, rye, oats, rice, maize, sorghum and related crops), beet (sugar beet and fodder beet) , pomes, drupes and soft fruit (appleš, pears, plums, peaches, almonds, cherries, stravberries, raspberries and blackberries), leguminous plants (beans, lentils, peas, soybeans), oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts), cucumber plants (cucumber, marrovs, melons), fibre plants (cotton, flax, hemp, jute), citrus fruit (oranges, lemons, grapefruit, mandarīns), vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, toroatoes, potatoes, paprika), lauraceae (avocados, cinnamon, camphor), or plants such as tobacco, nuts, coffee, sugar cane, tea, pepper, vines, hops, bananas and natūrai rubber plants, as well as ornamentals.

The compounds of formula I are normally applied in the forra of composi-tions and can be applied to the crop area or plant to be treated, simul-taneously or in succession, with further active substances. These active substances can be fertilisers or micronutrient donors or other prepara-tions that influence plant growth. They can also be selective herbicides, insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application-promoting adjuvants customarily employed in the art of formulation.

Suitable carriers and adjuvants can be solid or liquid' and correspond to the substances ordinarily employed in formulation technology, e.g. natūrai or regenerated roineral substances, solvents, dispersants, vetting aģents, tackiflers, thickeners, binders or fertilisers. A preferred method of applying a compound of formula I, or an agro-chemical composition vhich contains at least one of said compounds, is foliar application. The number of applications and the rāte of applica-tion depend on the risk of infestation by the corresponding pathogen. Hovever, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) if the ločus of the plant is impregnated with a liquid formulation, or if the compounds are applied in 20 solid form to the soil, e.g. in granular form (soil application). In paddy rice crops, such granulates may be applied in metered amounts to the flooded rice field. The compounds of formula I may, hovever, also be applied to seeds (coating) either by impregnating the seeds with a liquid formulation containing a compound of formula I, or coating them with a solid formulation.

The compounds of formula I are used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation, and are for this purpose advantageously formulated in known manner e.g. into emulsifiable concentrates, coatable pastes, directly sprayable or dilutable Solutions, dilute emulsions, vettable povders, soluble powders, dusts, granulates, and also encapsulations in e.g. polymer substances. As with the nature of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring,. are chosen in accordance with the intended objectives and the prevailing circumstances. Advantageous rātes of application are normally from 50 g to 5 kg of active ingredient (a.i.) per hectare, preferably from 100 g to 2 kg a.i./ha, most preferably from 200 g to 600 g a.i./ha.

The formulations, i.e. the compositions, preparations or mixtures containing the compound (active ingredient) of formula I and, vhere appropriate, a solid or liquid adjuvant, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredients with extenders, e.g. solvents, solid carriers and, where appropriate, surface-active compounds (surfactants).

Suitable solvents are: aromatic hydrocarbons, preferably the fractions containing 8 to 12 carbon atoms, e.g. xylene mixtures or substituted naphthalenes, phthalates such as dibutyl phthalate or dioctyl phthalate, aliphatic hydrocarbons such as cyclohexane or paraffins, alcohols and glycols and their ethers and esters, such as ethanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones such as cyclohexanone, strongly polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, a.s well as vegetable oile or epoxidised vegetable oils, such as epoxidised coconut oil or soybean oil; or water. - 21 - LV 10556

The solid carriers used e.g. for dusts and dispersible powders are normally natūrai mineral fillers, such as calcite, talcum, kaolin, raontmorillonite or attapulgite· In order to improve the physlcal properties it is also possible to add highly dispersed silicic acid or highly dispersed absorbent polymers. Suitable granulated adsorptive carriers are porous types, for example puraice, broken brick, sepiolite or bentonite; and suitable nonsorbent carriers are, for example, calcite or eand. In addition, a great number of pregranulated materiāls of inorganic nature can be used, e.g. especially dolomite or pulverised plant residues.

Particularly advantageous application-promoting adjuvants which are able to reduce substantially the rāte of application are also natūrai (animal or vegetable) or synthetic phospholipids of the series of the cephalins and lecithins, which can be obtained e.g. from soybeans.

Depending on the nature of the compound of formula I to be formulated, suitable surface-active compounds are non-ionic, cationic and/or anionic surfactants having good emulsifying, dispersing and vetting properties. The term "surfactants'* will also be understood as comprising mixtures of surfactants.

Both so-called water-soluble soaps and also vater-soluble synthetic surface-active compounds are suitable anionic surfactants.

Suitable soaps are the alkali mētai salts, alkaline earth mētai salts or unsubstituted or substituted ammonium salts of higher fatty acids (Cio—C22), e.g. the sodlura or potassium salts of olelc or stearic acid or of natūrai fatty acid mixtures which can be obtained e.g. from coconut oil or tallow oil. Hention may also be made of fatty acid methyllaurin salts.

More frequently, however, so-called synthetic surfactants are used, especially alkanesulfonates, fatty alcohol sulfates, sulfonated benzimidazole derivatives or alkylsulfonates. 22

The fatty alcohol sulfonates or sulfates are usually in the form of alkali mētai salts, alkaline earth mētai salts or unsubstituted or sub-stituted ammonium salts and contain a Ce~C22alkyl radical vhich also includes the alkyl moiety of acyl radicals, e.g. the sodium or calcium salt of lignosulfonic acid, of dodecylsulfate or of a mixture of fatty alcohol sulfates obtalned fro m natūrai fatty acids» These compounds also comprise the salts of sulfated and sulfonated fatty alcohol/ethylene oxide adducts. The sulfonated benzimidazole derivatives preferably contain 2 sulfonic acid groups and one fatty acid radical containing 8 to 22 carbon atoms. Examples of alkylarylsulfonates are the sodium, calcium or triethanolamine salts of dodecylbenzenesulfonic acid, dibutylnaphtha-lenesulfonic acid, or of a condensate of naphthalenesulfonic acid and formaldehyde.

Also suitable are corresponding phosphates, e.g. salts of the phosphoric acid ester of an adduct of p-nonylphenol with 4 to 14 moles of ethylene oxide.

Non-ionic surfactants are preferably polyglycol ether derivatives of aliphatic or cycloaliphatic alcohols, or saturated or unsaturated fatty acids and alkylphenols, said derivatives containing 3 to 30 glycol ether groups and 8 to 20 carbon atoms in the (aliphatic) hydrocarbon moiety and 6 to 18 carbon atoms in the alkyl moiety of the alkvlphenols.

Further suitable non-ionic surfactants are the water-soluble adducts of polyethylene oxide with polypropylene glycol, ethylenediaminopolypropy-lene glycol and alkylpolypropylene glycol containing 1 to 10 carbon atoms in the alkyl chain, which adducts contain 20 to 250 ethylene glycol ether groups and 10 to 100 propylene glycol ether groups. These compounds usually contain 1 to 5 ethylene glycol units per propylene glycol unit.

Representative examples of non-ionic surfactants are nonylphenolpoly-ethoxyethanols, castor oil polyglycol ethers, polypropylene/polyethylene oxide adducts, tributylphenoxypolyethyleneethanol, polyethylene glycol and octylphenoxypolyethoxyethanol.

Fatty acid esters of polyo.xyethylene sorbitan, e.g. polyoxyethylene sorbitan trioleate, are also suitable non-ionic surfactants. - 23 - LV 10556

Cationic surfactants are preferably quaternary ammonium salts vhich contain, as N-substituent, at least one Ca-C22alk'yl radlcal and, as further substituents, unsubstituted or halogenated lower alkyl, benzyl or hydroxy-lower alkyl radicals. The salta are preferably in the form of halides, methvlsulfātes or ethylsulfātes, e.g. stearyltrimethylammonium chloride or benzyldi( 2-chloroethyl)aminonium bromide.

Further surfactants customarily employed ln the art of formulation are known to the person skilled in the art or can be taken from the relevant speciālist literature.

The agrochemical compositions usually contain 0.1 to 99 %, preferably 0.1 to 95 %, of a compound of formula I, 99.9 to 1 %, preferably 99.9 to 5 %, of a solid or liquid adjuvant, and 0 to 25 %, preferably 0.1 to 25 %, of a surfactant.

Whereas coramercial products will preferably be formulated as concen-trates, the end user will normally employ dilute formulations.

The compositions may also contain further auxiliaries such as stabi-lisers, antifoams, viscosity regulators, binders, tackifiers as well as fertilisers or other active ingredients for obtaining special effects.

The folloving Examples serve to illustrate the invention in greater detail, vithout limiting it. 1. Preparation Examples

Example 1.1: Preparation of 2-phenylamino-4-methyl-6-cyclopropylpyrimi- dine CHj [Corap. no. 1.1] < )—NH~<W > ·=· ·Ν=· • — · 1/ 24 10 g (51 mmol) of phenylguanidine hvdrogen carbonate and 9.7 g (77 mmol) of l-cyclopropyl-l,3-butanedione are heated at 110°C for 6 hours with stirring, the evolution of carbon dioxide which o'ccurs subsidlng as the reaction progresses. After the dark brown emulsion has been cooled to room temperature, 50 ml of diethyl ether are added and the mixture is washed twice with 20 ml of vater each time, dried over sodium sulfate and filtered, and the eolvent is evaporated. The dark brown oil which remains ( 13.1 g) is purified by column chromatography over silica gel (diethyl ether/toluene: 5/3). After the eluant mixture has been evaporated off, the brovn oil is made to crystallise and recrystallised from diethyl ether/petroleum ether at 30-50β0. Light-brown crystals are obtained. Melting point: 67-69°C; yield: 8.55 g (38 mmol) (* 74.5 % of the theoretical yield).

Example 1.2: Preparation of 2-anilino-4-formyldiethyl-acetal-6-cyclo— propylpyrimidine . — . M— · < ;-nh-sm > ·=· N=*^ CH(OC2H5)2 1/ 11.7 g (59.2 mmol) of phenylguanidine hvdrogen carbonate and 13.3 g (62.2 mmol) of l-cyclopropyl-3-formyldiethylacetal-l,3-propanedione in 40 ml of ethanol are heated under reflux for 5 hours with stirring, the evolution of carbon dioxide subsiding as the reaction progresses. After the dark brovn emulsion has been cooled to room temperature, 80 ml of diethyl ether are added and the mixture is washed tvice vith 30 ml of vater each time, dried over sodium sulfate and filtered, and the solvent is evaporated. The dark brovn oil vhich remains (17 g) is purified by column chromatography over silica gel (toluene/ethyl acetate: 5/2). After the eluant mixture has been evaporated off, a reddish brovn oil remains vhich has a refractive index n^5: 1.5815. Yield: 15 g (48 mmol; 81.1 % of the theoretical yield). LV 10556 - 25 -

Example 1.3:

Pceparation of 2-anilino-4-fortnyl-6-cyclo-propylpyrimidine

\ v /N—·<" -NH- N=·'

CHO (Comp. no. 2.1) 1/ 12.3 g (39.3 mmol) of 2-anilino-4-formyldiethylacetal-6-cyclopropyl-pyrimidine, 4 g (39.3 mmol) of concentrated hydrochloric acid and 75 ml of water are heated at 50°C for 14 houcs with vigorous stirring and, after the addition of 2 g (19.6 mmol) of concentrated hydrochloric acid, stirring is continued for a further 24 hours at that temperature. After the beige-coloured suspension has been cooled to room temperature, 50 ml of ethyl acetate are added thereto and the mixture is rendered neutral with 7 ml of 30 % sodium hydroxide solution. The ethyl acetate solution is then separated off, dried over sodium sulfate and filtered, and the solvent is evaporated. For purification, the brovnish solid is re-crystallised from 20 ml of isopropanol in the presence of active carbon. The yellowish crystals melt at 112-114°C. Yield: 7.9 g (33 mmol; 84 % of the theoretical yield).

Example 1.4: Preparation of 2-anilino-4-hydroxymethyl-6-cyclopropyl-pyrlmidine

CH20H (Comp. no. 1.48) 1/ a) 2.3 g (60 mmol) of sodium borohydride are added in portions at room temperature, within a period of 15 minūtes, with stirring, to 14.1 g (59 mmol) of 2-anilino-4-formyl-6-cyclopropylpyrimidine in 350 ml of absolute methanol, vhereupon the reaction mixture varas up to 28°C with evolution of hydrogen. After 4 hours the mixture is acidified by the dropvise addition of 10 ml of concentrated hydrochloric acid, 120 ml of 10 % sodium hydrogen carbonate solution are added dropvtise, and the mixture is then diluted with 250 ml of vater. The resulting precipitate is filtered off, dried, largely dissolved in 600 ml of diethyl ether at elevated temperature, treated with active carbon and filtered. The clear filtrate is 26 concentrated until it becomes turbid and is then diluted with petroleura ether, and the light-yellow crystalline powder is filtered off; ra.p. 123-125°C. Yield: 10.8 g (44.8 mmol; 75.9 % of the theoretical yield). b) 5.9 g (23 mmol) of 2-anilino-4-methoxymethyl-6-cyclopropylpyrimidine, prepared from phenylguanidine and l-cyclopropyl-4-methoxy-l,3-butane-dione, are dissolved in 200 ml of dichloromethane and the solution is cooled to -68°C. 6.8 g (27 mmol) of boron tribromide are slowly added dropvise to the salmon-coloured solution within a period of half an hour, with vigorous stirring, and the cooling bath i9 then removed and stirring is continued for a further 2 hours at room temperature. After the addi-tion of 150 g of ice-water, the precipitated crude product is filtered off and recrystallised from methanol using active carbon. The light-yellow crystals melt at 124-126°C. Yield: 4.7 g (19.5 mmol; 84.7 % of the theoretical yield).

Example 1.5:

Preparation of 2-phenylamino-4-bromomethyl-6-cyclopropyl-pvrimidine •-NH—

/ \ ^CHsBr (Comp. no. 1.4) 1/ 15.6 g (75 mmol) of thionyl bromide in 50 ml of diethyl ether are added dropvise within a period of half an hour, with stirring, to 12 g (50 mmol) of 2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimidine and 0.4 g (50 mmol) of pyridine in 350 ml of diethyl ether. After stirring for 2 hours at room temperature, a further 0.4 g (50 mmol) of pyridine are added and the mixture is heated under reflux for 5 hours. After cooling to room temperature, 200 ml of water are added and the pH is adjusted to 7 by the dropvise addition of 140 ml of saturated sodium hydrogen carbonate solution. The diethyl ether phase is separated off and then vashed twice with 100 ml of water each time, dried over sodium sulfate and filtered, and the solvent is evaporated. The brown oil which remains is purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50-70°C): - 27 - LV 10556 5/3/1/1). After the eluant mixture has been evaporated off, the yellow oil is diluted with diethyl ether/petroleum ether (b.p. 50-70°C) and crystallised at reduced.temperature. The yellow crystalllne povder melts at 77.5-79.5°C. Yield: 9.7 g (32 mmol; 64 % of the theoretical yield).

Example 1.6: Preparation of 2-phenylamino-4-fluoromethyl-6-cyclopropyl-pvrimidine

-NH— N= / I » \ ,ch2f (Comp. no. 1.59) * — · \/ a) 3.9 g (12.8 mmol) of 2-phenylamino-4-bromomethyl-6-cyclopropylpyrirai-dine, 1.5 g (26 mmol) of spray-dried potassium fluoride and 0.3 g (1.13 mmol) of 18-Crown-6-ether are heated under reflux for 40 hours in 50 ml of acetonitrile. A further 0.75 g (13 mmol) of potassium fluoride is then added and the mixture is heated for 22 hours. To complete the reaction, a further 0.75 g (13 mmol) of spray-dried potassium fluoride and 0.1 g (0.38 mmol) of 18-Crown-6-ether are added and the mixture is heated under reflux for a further 24 hours. After the suspension has been cooled to room temperature, 150 ml of diethyl ether are added and the mixture is washed three times with 20 ml of vater each time, dried over sodiura sulfate and filtered, and the solvent is evaporated. The brown oil which remains is purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50-70eC): 5/3/1/1). After the eluant mixture has been evaporated off, the yellow oil is diluted with 10 ml of petroleum ether (b.p. 50-70°C) and crystallised at reduced temperature. The yellow crystals melt at 48-52°C; yield: 2.1 g (8.6 mmol); 67.5 % of the theoretical yield. b) 6.1 g (37.8 mmol) of diethylaminosulfur trifluoride in 15 ml of di-chloromethane are slowly added dropvrise vithin a period of one hour, with stirring, to a suspension of 9.1 g (37.8 mmol) of 2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimidine in 80 ml of dichloromethane. After the addition of 50 ml of ice-water, 50 ml of 10 % aqueous sodium hydrogen carbonate solution are added dropwise. When the evolution of carbon dioxide has ceased, the organic phase is separated off and the aqueous 28 phase is extracted twice with 20 ml of dichloromethane each time. The combined dichloromethane Solutions are washed with 15 ml of water, dried over sodium sulfate and filtered, and the solvent is evaporated. The black oil which remains is purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50-70°); 5/3/1/1). After the eluant mixture has been evaporated off, the yellow oil is diluted with 20 ml of petroleum ether (b.p. 50-70°C) and crystallised at reduced temperature. The yellowish crystals melt at 50-52eC. Yield: 4.9 g (20.1 mmol; 53 % of the theoretical yield).

Example 1.7: Preparation of 2-hydroxy-4-methyl-6-cyclo-propylpyrimidine

H—'' / X XK .CH3 HO- ♦ — · t/ 15 ml of concentrated hydrochloric acid are added at room temperature to 6 g (100 mmol) of urea and 12.6 g (100 mmol) of l-cyclopropyl-l,3-butane-dione in 35 ml of ethanol. After the mixture has stood for 10 days at room temperature, it is concentrated in a rotary evaporator at a bath temperature not exceeding 45°C. The residue is dissolved in 20 ml of ethanol, the hydrochloride of the reaction product precipitating after a short time. 20 ml of diethyl ether are added with stirring, and the precipitated white crystals are filtered off, vashed with an ethanol/diethyl ether mixture and dried. Concentration of the filtrate and recrystallisation from an ethanol/diethyl ether mixture: 1/2 yield a further quantity of hydrochloride. The white crystals melt > 230°C.

Yield: hydrochloride 12.6 g (67.5 mmol; 67.5 % of the theoretical yield).

Example 1.8: Preparation of 2-chloro-4-methyl-6-cyclo-propylpyrimldine

I —· 1/ (Comp. no. 3.1) - 29 - LV 10556 52.8 g (0.24 mol) of 2-hydroxy-4-methyl-6-cyclopropylpyrimidine hydroc-hloride are introduced at room temperature, with stirring, into a mixtur> of 100 ml (1.1 mol) of phosphorus oxychloride and 117 g (0.79 mol) of diethylaniline, the temperature rising to 63°C. After the mixture has been heated for 2 hours at 110°, it is cooled to room temperature and transferred onto an ice~water/methylene chloride mixture, with stirring. The organic phase is separated off and vashed with saturated aqueous sodium hydrogen carbonate solution until neutral. Removal of the solvent by evaporation yields 116.4 g of oil, which is composed of the reaction product and diethylaniline. Separation of the diethylaniline and purifi-catlon of the crude reaction product are effected by column chromato-graphy over silica gel (hexane/diethyl acetate: 3/1). The colourless oil which crystallises after several days has a refractive index : 1.5419; yield: 35.7 g (0.21 mol; 87.5 % of the theoretical yield); melting point: 33-34°C.

Example 1.9: Preparation of 2-(m-fluorophenylamino)-4-roethyl-6-cyclo-propylpyrimidine • — . M— · ^< >—·ς ) ,ch3 (Comp. no. 1.63) 1/ A solution of 5.5 g (50 mmol) of 3-fluoroaniline and 9.3 g (55 rnmol) of 2-chloro-4-methyl-6-cyclopropylpyrimidine in 100 ml of ethanol is adjusted to pH 1 with 5 ml of concentrated hydrochloric acid, with stirring, and is then heated under reflux for 18 hours. After the brown eraul-sion has been cooled to room temperature, it is rendered alkaline with 10 ml of 30 % ammonia, poured onto 100 ml of ice-water and extracted twice with 150 ml of diethyl ether each time. The combined extracts are vashed with 50 ml of water, dried over sodium sulfate and filtered, and the solvent is evaporated. The yellowish crystals vhich remain are puri-fied by recrystallisation from diisopropyl ether/petroleum ether (b.p. 50-70°C). The white crystals melt at 87-89°C; yield: 8.3 g (34 mmol; 68 % of the theoretical yield). - 30 -

The folloving compounds of formula I can be prepared in this manner or by one of the methods described hereinbefore .

01 I I LV 10556 i

T //\ • ·

I II >x ftS &

Table 1: Compounds of the formula r\ // \ / * i ·

I CO *

Continuation: Table

ILV 10556

co on I

Continuation: Table

I <r cn i

Continuation: Table

LV 10556 m m i

Continuation: Table

\ vO

Continuation: Table

I r-. cn LV 10556

Continuatlon: Table

I co co i

Continuation: Table

LV 10556

σ\ co I

Continuation: Table

o

Continuation: Table

1LV 10556 ļ

Continuation: Table

1 CN I

Continuation: Table

I cn < LV 10556

Continuation: Table

I < I

Continuation: Table

ILV 10556

Continuation: Table

I vO

Continuation: Table

I i LV 10556

I 00 <r

Continuation: Table

LV 10556

t < I

Continuation: Table

I 0 LO 1

Continuation: Table

LV 10556

Continuation: Table

I CNJ ιΛ I

Continuation: Table

ILV 10556

ΓΊ in I

Continuation: Table

I vr ιΛ I

Continuation: Table

ILV 10556

ιΛ m I

Continuation: Table

I vO VO

Continuation: Table

LV 10556

Continuation: Table

I 00 ιΛ

Continuation: Table

iLV 10556

θ' u-> I

Continuation: Table

I o VO

Continuation: Table

LV 10556 - 61 -

In Tablea 2, 3 and.4 intermediate products, according to the invention, are exemplified.

Table 2: Compounda of the formula

Ri V\ -NH- N=

^CHO \

RZ

Comp. no. Ri r2 R- Phvsical constant 2.1 H H • A \ļ m. p. 112-114UC /C1 • 2.2 H H -<! m. p. 1 2 3-12 7 °C /CHj • 2.3 H H -<l • m. p. 87-90°C 2.4 4-C1 H • -<l / • 2.5 H H -<l • tn. p. 128-132°C 2.6 3-F H -<i • 2.7 4-F H • -<l • 62 Table 3:

Hal- v< R3

Ru Comp. Hal R3 R<* Physical no. cons tant 3.1 C1 -CHj / — · \ /CHa m.p. 33-34°C 3.2 C1 -CH j / **— t \ oil; : 1.5432 3.3 C1 -CH3 1 /\ \> / 3.4 C1 -ch3 3.5 C1 -ch3 • 0 t 3.6 C1 -C3H7 -i \ / • 1 3.7 C1 • -<l • - —· · — \ —— « / 3.8 C1 ~CH2— CH3 ČH-CHj -< /CH3 3.9 C1 _A \! • / — · \ yCH3 > 3.10 Br —CH3 -< ► - 63 -LV 10556

Table 3: Continuation Comp. no. Hal R3 Rg Physical constant 3.11 C1 H • -<! 3.12 C1 —CuHg-n A \ļ 3.13 C1 -CHClz A \l 3.14 C1 -ch3 JA ”\ļ /Br 3.15 C1 -ch3 -<! /C1 3.16 C1 —CH3 A \ļ xci /0Η3 3.17 C1 -CiHs A \ļ m.p. 32-35°C 3.18 C1 -CF2CFj -<! / 3.19 C1 —CHj A \ļ xci / 3.20 Br -ch3 -<i 64

Table 3: Continuation

Comp. Hal Rz Rk Physical no. constant 3.21 C1 -c2h5 / — * \ > m.p. 28-31°C 9Hi 3.22 C1 -CHj 1 A » 3.23 C1 —C14H9—sek. > » 3.24 C1 —CHj / — · \ m. p. 42-45°C 3.25 C1 A \l • 1/ /C1 3.26 C1 -CHj -< V » ĪH- /C1 3.27 C1 —CH 3 1/ \ xci yCH} ^CHj 3.28 C1 /\ \l • _/ \ 3.29 Br -ch3 4 /C1 3.30 Br -CHj / — · \ - 65 -LV 10556

Table 3: Continuation Comp. Hal Rj R« Physical no. constant 3.31 C1 —C 3 H 7—n -< I 3.32 C1 -ch3 / — · \ — · \ • / /CH3 3.33 Br -c2h5 ~C 3.34 C1 —CF 3 / «— · 3.35 Br —CjHs -< /C1 3. 36 C1 -ch3 / * \ /F 3.37 C1 —ch3 *\ nf /CHj 3.38 C1 —ch3 -< nch3 3.39 C1 —CC1F 2 - -< 3.40 C1 • \l • -< 3.41 C1 —CHjCl -< 3.42 C1 -ch2f -< 3.43 Br • -<l • -< 3.44 Br -ch2f -< 3.45 C1 -ch2oh -<i « 66

Comp. no - Hal Rj. Rm Physical constant 3.46 Br -ch2oh « '/1 \l • i - 67 - Table 4:

,N R5S02- V. / LV 10556 N= Comp. R$ Rj R- Physical no. cons tant • /1 4.1 ch3 —€H3 -\l • 4.2 ch3 —ch3 • / \ — · · \ / • 4.3 C i* H 9 -n —ch3 • \l 4.4 ch3 —ch3 \l • 4.5 * — · CH*-< )' —CH 3 • .11.1. \ / • 1 t s · • /r • 4.6 ch3 —€H3 \l • 4.7 • —· ♦ —CHs—' /*-CH3 —€H3 • /\ *\| i S » • / • 4.8 c2hs -ch3 \l • C1 / 4.9 ch3 —CHj -<r* • /CH3 • • 4.10 ch3 \ / • 1 -<l m.p. 84-89°C • • 68

Table 4: Continuation

Comp. Rs Rj R« Physical no. constant 4.11 CH2-·^ /·-C1 —CH j -< » • “ · /CHj 4.12 CHj —CHj / · \ 4.13 CHj -CHj L· — · \ /F 4.14 CHj -CHj / \ xci /C1 4.15 C2H5 -CHj / \ 4.16 CHj -c2h5 \ / • 1 m.p. 64-68uC 4.17 CjH5 —CHj « / — · \ 1 4.18 C j H 7—n -CH j -< CHj 4.19 CHj —CH j 1 / · \ 1 /CHj 4.20 C j H 7— n -CHj -< « - 69 -LV 10556

Table 4: Continuation

70 2. Formulation Exampl.es for liguid active ingredients of formula I (throughout, percentages are by veight) 2.1. Emulsifiable concentrates a) b) c) a compound of Table 1 25 % 40 % 50 % calcium dodecylbenzenesulfonate 5 % 8 % 6 % castor oil polyethylene glycol ether (36 raoles of ethylene oxide) 5 % tributylphenol polyethylene glycol ether (30 moles of ethylene oxide) 12 % 4 % cyclohexanone - 15 % 20 % xylene mixture 65 % 25 % 20 % Emulsions of any desired concentration can be produced from such concentrates by dilution with water • 2.2. Solutions a) b) c) d) a compound of Table 1 80 % 10 % 5 % 95 % ethylene glycol monomethyl ether 20 % - - polyethylene glycol (mol. wt. 400) - 70 % - N-methyl-2-pyrrolidone - 20 % - epoxidised coconut oil - - 1 % 5 % Petroleum fraction (boiling range 160-190°C) - - 94 % - These Solutions are suitable for application in the form of micro-drops 2.3. Granulates a) b) a compound of Table 1 5 % 10 % kaolin 94 % - highly dispersed silicic acid 1 % - attapulgite - 90 % - 71 - LV 10556

The active ingredient is dissolved in methylene chloride, the solution is sprayed onto the carrier, and the solvent is subsequently evaporated off in vacuo. 2.4. Du s t s a) b) a compound of Table 1 2 % 5 % highly dispersed silicic acid 1 % 5 % talcum 97 % - kaolin - 90 % Ready-for-use dusts are obtained by intimately mixing the carriers with the active ingredient. Formulation Examples for solid active ingredients of formula I (through- out, percentages are by veight) 2.5. Wettable povders a) b) c) a compound of Table 1 25 % 50 % 75 % sodium lignosulfonate 5 % 5 % - sodium laurylsulfate 3 % - 5 % sodium diisobutylnaphthalene-sulfonate . 6 % 10 % octylphenol polyethylene glycol ether (7-8 moles of ethylene oxide) . 2 % highly dispersed silicic acid 5 % 10 % • 10 % kaolin 62 % 2 7 %

The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording vettable povders vhich can be diluted with water to give suspensions of the desired concentration. 2.6. Emulsifiable concentrate a compound of Table 1 10 % octylphenol polyethylene glycol ether (4-5 moles of ethylene oxide) 3 % ♦ - 72 - calcium dodecylbenzenesulfonate 3 % castor oil polyglycol ether (35 moles of ethylene oxide) 4 % cyclohexanone 34 % xylene mixture 50 %

Emulsions of any required concentration can be obtained from this concen-trate by dilution with water. 2.7. Dusts a) b) a compound of Table 1 5 % 8 % talcum 95 % - kaolin - 92 %

Ready-for-use dusts are obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable mill. 2.8. Extruder granulate a compound of Table 1 10 % sodium lignosulfonate 2 % carboxymethylcellulose 1 % kaolin 87 %

The active ingredient is mixed and ground with the adjuvants, and the mixture is subsequently moistened with water. The mixture is extruded and then dried in a stream of air. 2.9. Coated granulate a compound of Table 1 3 % polyethylene glycol (mol. wt. 200) 3 % kaolin 94 %

The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granu-lates are obtained in this manner. - 73 - LV 10556 2.10. Suspension concentrate a compound of Table 1 40 % ethylene glycol 10 % nonylphenol polyethylene glycol ether (15 moles of ethylene oxide) 6 % sodium lignosulfonate 10 % carboxymethylcellulose 1 % 37 % aqueous formaldehyde solution 0.2 % silicone oil in the form of a 75 % aqueous emulsion 0.8 % uater 32 %

The finely ground active ingredient is intimately mixed with the adju-vants, giving a suspension concentrate from which suspensions of any desired concentration can be obtained by dilution with water. 3. Biological Examples

Exaniple 3.1: Action against Venturia inaegualis on apple shoots Residual protective action

Apple cuttings with 10-20 cm long fresh shoots are sprayed with a spray mixture (0.006 % active ingredient) prepared from a vettable powder for-mulation of the tēst compound. The treated plants are infected 24 hours later vith a conidia suspension of the fungus. The plants are then incu-bated for 5 days at 90-100 % relative humidity and stood in a greenhouse for a further 10 days at 20-24°C. Scab infestation is evaluated 15 days after infection.

Compounds of Table 1 exhibit good activity against Venturia (less than 20 % attack). Thus e.g. compounds nos. 1.1, 1.6, 1.13, 1.14, 1.59, 1.66, 1.69, 1.84, 1.87, 1.94, 1.108, 1.126, 1.145, 1.158, 1.180, 1.200 and 1.236 reduce Venturia attack to 0 to 10 %. On the other hand, Venturia attack is 100 % in untreated and infected control plants. 74

Example 3.2: Action against Botrytis cinerea on appleš Residual protective action

Artificially damaged appleš are treated by the dropvise application to the damaged sites of a spray mixture (0.002 % active lngredient) prepared from a vettable powder formulation of the tēst compound. The treated fruits are then inoculated with a spore suspenslon of the fungus and incubated for one week at high humidity and about 20°C. Evaluation ie made by counting the rotted damaged sites and deriving the fungicidal activity of the tēst compound therefrom.

Compounds of Table 1 exhibit good activity against Botrytis (less than 20 % attack). Thus e.g. compounds nos. 1.1, 1.6, 1.13, 1.14, 1.31, 1.33, 1.35, 1.48, 1.59, 1.66, 1.69, 1.84, 1.87, 1.94, 1.108, 1.126, 1.131, 1.145, 1.158, 1.180 and 1.236 reduce Botrytis attack to 0 to 10 %. On the other hand, Botrytis attack is 100 % on untreated and infected control plants.

Example 3.3: Action against Ervsiphe graminis on barley Residual protective action

Barley plants about 8 cm in height are spraved with a spray mixture (0.006 % active ingredient) prepared from a vettable povder formulation of the tēst compound. The treated plants are dusted with conidia of the fungus after 3 to 4 hours. The infected barley plants are stood in a greenhouse at about 22°C. The fungus attack is evaluated after 10 days.

Compounds of Table 1 exhibit good activity against Ervsiphe (less than 20 % attack). Thus e.g. compounds nos. 1.1, 1.6, 1.13, 1.14, 1.35, 1.48, 1.59, 1.66, 1.69, 1.84, 1.87, 1.94, 1.108, 1.131, 1.158 and 1.236 reduce Erysiphe attack to 0 to 10 %. On the other hand, Erysiphe attack is 100 % on untreated and infected control plants.

Example 3.4: Action against Helmlnthosporium gramineum

Wheat grains are contaminated with a spore suspension of the fungus and dried. The contaminated grains are dressed with a suspension of the tēst compound prepared from a vettable povder (600 ppm of active ingredient, based on the veight of the seeds). Two days later the grains are placed - 75 - LV 10556 in suitable agar dishes and the development of fungus colonies around the grains is assessed after another 4 days. The effectiveness of the tēst compounds is evaluated on the basis of the number and size of the colonies. The compounds of the Table substantially prevent fungus attack (0 to 10 %).

Example 3.5: Action against Colletotrlchum lagenarium on cucumbers After a cultivation period of two weeks, cucumber plants are sprayed wlth a spray mixture (concentration 0.002 %) prepared from a wettable powder formulation of the tēst compound. After two days the plants are infected with a spore suspension (1.5 x 105 spores/ml) of the fungus and incubated for 36 hours at 23°C and high humidity. Incubation is then continued at nomal humidity and about 22-23°C. Evaluation of fungus attack is made 8 days after infection. Fungus attack is 100 % on untreated and infected control plants.

Compounds of Table 1 exhibit good activity and inhibit the spread of the disease. Fungus attack is reduced to 20 % or less.

Example 3.6: a) Contact action against Nephotettix cincticeps and Nila-parvata lugens (nymphs)

The tēst is carried out with grow.ing rice plants. For this purpose 4 plants (14-20 days old) about 15 cra in height are planted into each of a number of pots (diameter 5.5 cm).

The plants are sprayed on a rotary table with 100 ml of an aqueous emul-sion preparation containing 400 ppm of the tēst compound. After the spray coating has dried, each plant is populated with 20 nymphs of the tēst organisms in the third stage. To prevent the cicadas from escaping, a glass cylinder vhich is open at both ends is slipped over each of the plants and sealed with a gauze top. The nymphs are ķept on the treated plants for 6 days until they have reached the adult stage. An evaluation is made on the basis of percentage mortality 6 day3 after population of the plants. The tēst is carried out at about 27°C and 60 % relative humi— ditv. The plants are exposed to light for a period of 16 hours per day. 76 b) Systemlc action against Nilaparvata lugens (in.water)

Rice plants about 10 days old (about 10 cm high) are placed in a plastics beaker which contains 150 ml of an aqueous emulsion preparation of the tēst compound in a concentration of 100 ppm and is closed by a perforated plastics lid. The rootc of each of the rice plants are pushed through a hole in the plastics lid into the aqueoua tēst preparation. Then the rice plants are populated wiuh 20 nymphs of Nilaparvata lugens in the N2 to N3 stage and covered with a plastics cylinder. The tēst is carried out at about 26°C and 60 % relative humidity, and the plants are exposed to light for a period of 16 hours por day. After five days the number of dead tēst organisms is assessed in comparison uith untreated Controls. It is thus established vhether the tēst substance absorbed via the roots kills the tēst organisms at the upper parts of the plants.

Compounds of Table 1 exhibit a pronounced killing action on the rice pests both in tēst a) and in tēst b). The mortality rāte is 80 % or above. Alraost total mortality (98-100 %) was achieved with compounds nos. 1.1, 1.6, 1.14, 1.59, 1.66, 1.87, 1.94, 1.108 and 1.236. LV 10556

What is claimed is: A method of controlling or preventing an attack on cultivated plants by harmful insects or phytopathogenic microorganisms, which comprises applying as active ingredient to the plant, to parts of plants or to the ločus thereof, a compound of formula I according to claim I.

R·* 3 in vvhich: Rļ and R2 independentlv of one another are hydrogen, halogen, C]-C3 alkyl, C[-C2 haloalkyl, CrC3 alkoxy or C,-C3 haloalkoxy; R3 is hydrogen; C,-C4 alkyl; or CrC4 alkyl substituted by halogen, hydroxy and/or cyano; cyclopropil; or cyclopropil mono- to tri-substituted by methyl and/or by halogen; and R4 is C3-C6 cycloalkyl or C3-C6 or cyclopropil mono- to tri-substituted by methyl and/or by halogen.

Advantageous rātes of application are normally from 50 g to 5 kg of active ingredient (a.i.) per hectare, preferably from 100 g to 2 kg a. i. /ha . LV 10556

ABSTRACT A compound of the formula

RK N=\ * ^ __/ \ \.~y W (I)

X \

Ru in which: and R2 independently of one another are hydrogen, halogen, Cļ_3-alkyl-, Cļ_2-haloalkyl-, Cļ_3~alkoxy- or Cj^-haloal-koxygroup; R3 is hydrogen, C^^-alkvl- or Cļ_4-alkylgroup substituted by halogen, hydroxygroup or cyanogroup, cyclopropylgroup or cyclopro-pylgroup independently of one another mono- to trisubstituted by methylgroup and/or halogen; R. is C_ ,-cycloalkylgroup or C0 ,-cycloalkylgroup independently of one another mono- to trisubstituted by methylgroup and/or halogen, possessing valuable microbicidal and insecticidal properties.

The novel active compounds can be used in protection of culti-vated plants from attack by phytopathogenic microorganisms or by harmful insects, and for controlling these pests.

Claims (1)

LV 10556 IZGUDROJUMA FORMULA Paņēmiens kaitīgu kukaiņu un fitopatogēno mikroorganismu radītu kultūraugu bojājumu apkarošanai vai novēršanai, kurš atšķiras ar to, ka augus, augu daļas vai to augšanas vietu apstrādā ar bioloģiski aktīvu vielu-2-anilīno-pirimidīna atvasinājumiem ar formulu (I), R τ v< Kz R·* kur: R, un R2 - neatkarīgi viens no otra, ir ūdeņradis, halogēns, CrC3 alkilgrupa, (VC2 halogēnalkilgrupa, CrC3 alkoksigrupa vai CrC3 halogēnalkoksigrupa, R3 ūdeņradis, CrC4 alkilgrupa, vai CrC4 alkilgrupa, kura aizvietota ar halogēnu, hidroksigrupu vai ciānogrupu; ciklopropilgrupa vai ciklopropilgrupa, kura, vienādi vai atšķirīgi, aizvietota līdz 3 reizēm ar metilgrupu un/vai halogēnu, R4 - C3-C6cikloalkilgrupa, vai C3-C6 cikloalkilgrupa, kura, vienādi vai atšķirīgi, aizvietota līdz 3 reizēm ar metilgrupu un/vai halogēnu, kuru lietošanas deva-50 g līdz 5 kg uz hektāru, optimāli no 100 g līdz 2 kg uz hektāru.A method for controlling or preventing damage to crops caused by harmful insects and phytopathogenic microorganisms, characterized in that the plants, parts of plants or their growth site are treated with biologically active substances-2-anilino-pyrimidine derivatives of formula (I), R τ v < Kz R · * where: R and R 2 are independently of one another hydrogen, halogen, C 1 -C 3 alkyl, (C 1-6 haloalkyl, C 1 -C 3 alkoxy or C 1 -C 3 haloalkoxy, R 3 hydrogen, C 1 -C 4 alkyl, or C 1-4 alkyl substituted with halogen, hydroxy) cyclopropyl or cyclopropyl, which is identical or differently substituted by up to 3 times with methyl and / or halogen, R4 - C3-C6cycloalkyl, or C3-C6 cycloalkyl, which is identical or differently substituted by up to 3 times with methyl and / or \ t or halogen with a dose of 50 g to 5 kg per hectare, preferably from 100 g to 2 kg per hectare.