CA1331759C - Pyrimidine derivatives useful in the preparation of pesticides - Google Patents

Abstract

ABSTRACT
A compound of the formula XXX
in which: R0 is halogen or R5-SO2-; R3 is hydrogen; C1-C4alkyl;
or C1-C4alkyl substituted by halogen, hydroxy or by cyano;
cyclopropyl; or cyclopropyl mono- to tri-substituted by methyl and/or by halogen; R4 is C3-C6cycloalkyl or C3-C6cycloalkyl mono-to tri-substituted by methyl and/or by halogen; and R5 is C1-C8alkyl or benzyl that is unsubstituted or substituted by halogen and/or by C1-C4alkyl. Compounds of this type are useful as intermediates in the preparation of pesticides.

Description

~ - t 33 1 75q This application is a first divisional application of application No. 578,360 filed on September 26th, 1~88. This application relates to compounds of formula XXX as defined below.
A second divisional application relates to compounds of formula XXI as defined below.
The invention of the parent application relates to novel 2-anilinopyrimidine derivatives of formula I below. It relates also to the preparation of those substances and to agro-chemical compositions that contain as active ingredient at least one of those compounds. It relates also to the preparation of the mentioned compositions and to the use of the active ingredients or of the compositions for controlling pests, especially harmful insects and plant-destructive microorganisms, preferably fungi.
The compounds of the general formula I are defined as follows:

+ ~ - N~

in which: Rl and R2 independently of one another are hydrogen, halogen, Cl-C3alkyl, Cl-C2haloalkyl, Cl-C3alkoxy or Cl-C3halo-.~ .
alkoxy; R3 is hydrogen; Cl-C4alkyl; or Cl-C4alkyl substituted by 20- halogen, hydroxy and/or cyano; cyclopropyl; or cyclopropyl mono-to tri-substituted by methyl and/or by halogen; and R4 is C3-C6-cycloalkyl or C3-C6cycloalkyl mono- to tri-substituted by methyl .
:` ~

and/or by halogen; including their acid addition salts and metal salt complexes.
Depending on the number of carbon atoms indicated, alkyl by itself or as a component of another substituent, such as haloalkyl, alkoxy or haloalkoxy, is to be understood as meaning, for example, methyl, ethyl, propyl, butyl and their isomers, such as, for example, isopropyl, isobutyl, 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, CHC12, CH2F, CC13, 2 2 3' CH2CH2Br' 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 Appliaation 0 224 339 and in GDR Patent Specification 151 404, compoundsthat 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 between the compounds of formula I and the known compounds is that at least one cyclo-alkyl radical and other substituents have been introduced into the anilinopyrimidine structure, as a result of which an unexpectedly high fungicidal activity and insecticidal action is obtained with the novel compounds.

, - ' -. :

~: :

- 2a - I 331 759 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 prevent-ively and curatively in the agricultural sector or related fields for controlling plant-destructive microorganisms. The compounds of formula I are distinguished at low application concentrations not only by excellent insecticidal and fungicidal action but also by the fact that they are especially well tolerated by plants.
The invention relates both to the free compounds of formula I and to their addition sal~s with inorganic and organic acids and to their complexes with metal salts.
Salts are especially addition salts with acceptable inorganic or organic acids, for example hydrohalic acids, for example hydrochloric, hydrobromic or hydriodic acid, sulfuric acid, phosphoric acid, phosphorous acid, nitric acid, or organic acids, such as acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, glycolic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid, oxalic acid, formic acid, benzenesulfonic ;:

^ 1 33 1 759 acid, p-toluenesulfonic acid, methane~ulfonlc acid, salicylic acid, p-aminosallcylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid or 1,2-naphthalenedisulfonic acid.

Metal salt complexes of formula I consist of the organic molecule on which they are based and an inorganic or organic metal salt, for example the halides, nitrates, sulfates, phosphates, acetates, trifluoroacetates, trichloroacetates, propionates, tartrates, sulfonates, salicylates, benzoates etc. of the elements of the second ~ain group, such as calcium and magnesium, and of the third and fourth main groups, such as alumi-nium, tin or l~ad, and of the fir~t to eighth subgroups, such as chromium, maDganese, iron, cobalt, nickel, copper, zinc etc. The sub-group elemeDts of the fourth period are preferred. The metals can be in any of their various valencie~. The metal complexes can be mono- or poly-nuclear, that i9 to say they can contain one or more organic molecu-lar moietie~ as ligaDds.

An important group of phytofungicides and in~3ecticides is formed by those of formula I ln which Rl and R2 are hydrogen.

A special group is formed by the following compounds of formula I in which:
Rl and R2 independently of one another are hydrogen, halogen, Cl-C3alkyl, C~-C2haloalkyl, Cl-C3alkoxy or Cl-C3haloalko~y; R3 1- hydrogen, Cl-C4alkyl or Cl-C4alkyl substituted by halogen or by cyano and R4 i9 C3-c6cycloal~yl or C3-C6cycloalkyl substi-tuted by m thyl or by halogen.

The followlng group~ of active ingredients are preforred because of their pronounced microbicidal, especially phytofungicidal, activity:

Group la: Compounds of formuls I in which:
'' Rl and Rz independently of one another are hydrogen, fluorine, chlorine, bromine, methyl, ethyl, halomethyl, methoxy, ethoxy or halomethoxy; R3 i9 hydrogen, methyl, methyl substituted by fluorine, chlorine, bro~ine or by '~

.

~^~
- ~S3175q cyano; ethyl, ethyl substituted by fluorine, chlorine, bromine or by cyano; n-propyl or ~ec.-butyl; and R4 is C3-C6cycloalkyl or C3-C6cyclo-alkyl substituted by methyl, fluorine, chlorine or by bromine.

Of the above-mentioned compounds, an especislly preferred group i9 formed by those in which R~ - R2 - hydrogen (- Group laa).

Group lb: Compound~ of formula I in which: ~

Rl and R2 independently of OnQ another are hydrogen, chlorine, bromine, methyl, ethyl, trifluoromethyl, methoxy, ethoxy or difluoro~ethoxy; R3 i9 hydrogen, methyl, methyl substituted by fluorine, chlorine or by cyano, ethyl or n-propyl and R4 i9 C3-Cscycloalkyl or C3-Cscycloalkyl ~ubsti-tuted by methyl or by chlorine.

Of the above-mentioned compounds, an especially preferred group i9 formed by those in which Rl - R2 - hydrogen (- Group lbb).

Group lc: Compounds of formula I in whlch:
,.
Rl and R2 independently of one another are hydrogen, chlorine, methyl, methoxy, ethoxy or trlfluoromethyl; Rl i9 hydrogen, methyl, ethyl or trlfluoromethyl; and R4 i- cyclopropyl or cyclopropyl sub~tituted by methyl or by chlor~n-.

Of the abov--aention-d compound~, an e~peci-lly preferred group i~ formed by thoAe in which Rl - R2 - hydrogen (- Group lcc).

Group ld: Compound~ of formula I in which:

Rl i9 hydrogen; R2 and Rj independently of one another sre hydrogen or methyl; and R4 i9 cyclopropyl or cyclopropyl substituted by methyl.

~; ~

Group 2a: Compound~ of formula I in which:

Rl and R2 independently of one another are hydrogen, halogen, Cl-C2alXyl, halomethyl, Cl-C2alkoxy or C~-C2haloalkoxy; R3 i9 hydrogen; Cl-C4alkyl;
Cl-C2alkyl substituted by halogen or by hydroxy; cyclopropyl; or cyclo-propyl mono- to tri-~ubstituted by Methyl and/or by halogen; and R4 i9 C3-C6cycloalkyl or C3-C4cycloalkyl mono- to tri-sub~tituted by m2thyl and/or by halogen.

Of the above-mentioned compounds, an especially preferred group i~ formed by those in which R~ - Rz - hydrogen (- Group 2aa~.

Group 2b: Compound~ of formula I in which:

Rl and R2 independently of one another are hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, methoxy or difluorometho~y; R3 i9 hydrogen; Cl-CJalkyl; Cl-C2alkyl substitutet by halogen or by hydroxy;
cyclopropyl; or cyclopropyl mono- to tri-subetituted by methyl andtor by halogen; and R4 iJ CJ-Cccycloalkyl or C3-C4cycloalkyl mono- to tri-3ub~
Jtltuted by methyl and/or by halogen.

Of the sbove-mentioned compound-, an eJpecially preferred group iJ formed by those in which Rl - R2 - hydrogen (- Group 2bb).

Group 2c: Co pound~ of formula I in which:

Rl and R2 intependently of on- another are hydrogen, fluorine, chlorine, methyl, trifluoromethyl, methoxy or difluoromethoxy; R3 iJ hydrogen;
Cl-C3alkyl; Cl-C2alkyl ~ub~tituted by halogen or by hydroxy; cyclopropyl;
or cyclopropyl mono- to tri-subJtituted by methyl andlor by halogen; and R4 iJ C3-C6cycloalkyl or C3-C4cycloalkyl mono-to tri-JubJtituted by methyl andlor by halogen.

Of the above-mentioned compound~, an eJpecially preferred group iJ formed by tho~3e in which Rl - R2 - hydrogen (- Group 2cc).

`~,' ' - ~ , ,., :

r~
1 ~3 1 7')~

Group 2t: Compound~ of formula I in which:

Rl and R2 are hydrogen; R3 i9 C1-C3alkyl; methyl substituted by fluorine, chlorine, bromine or by hydroxy; cyclopropyl; or cyclopropyl substituted by methyl, fluorine, chlorine or by bromine; and R4 is C3-C4cycloalkyl or C3-C4cycloalkyl mono- to tri-substituted by methyl and/or by fluorine, chlorine or by bromine.

Of the individual sub~tances that are especially preferred there ~eiy be mentioned, for exa~ple:
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-cyclopropylpyrlmidine (comp. no. 1.48);
2-phenylamino-4-fluoromethyl-6-cyclopropylpyrimldine (comp. no. 1.59);
2-phenylamino-4-hydroxymethyl-6-(2-methylcyclopropyl)-pyrimitine (comp. no. 1.13);
2-phenylamino-4-methyl-6-(2-fluorocyclopropyl)-pyrimidlne (comp. no. 1.66);
2-phenylamino-4-methyl-6-(2-chlorocyclopropyl)-pyrimidine (comp. no. 1.69);
2-phenylamlno-4-methyl-6-(2-difluorocyclopropyl)-pyrimidine (comp. no- 1.84?;
2-phenyl-mino-4-fluoromethyl-6-(2-fluorocyclopropyl)-pyrimidine (comp. no. 1.87);
2-phenyla~ino-4-fluoromethyl-6-(2-chlorocyclopropyl)-pyrimidin-(comp. no. 1.94);
2-phenylamino-4-fluoromethyl-6-(2-methylcyclopropyl)-pyrimidine (comp. no. 1.108);
2-phenylamino-4-ethyl-6-(2-methylcyclopropyl)-pyrimidine (comp. no. 1.131);
2-(p-fluorophenylamino)-4-methyl-6-cyclopropylpyrimidine (comp. no. 1.33).

1 7~ 3 1 759 The compounds of formula I are prepared as follows:

1. a phenylguanidine salt of formula IIa ~ NH - C~ A (IIa) or the free guanidine base of formula IIb ~ NH ~ ~IIb) i3 reacted with a diketone of formula III
Q R
R3--~ - CH2--~ - R4 (III) without solvents or in an aprotic solvent, preferably in a protic solvent, at temperatures of from 60C to 160C, preferably fro~ 60C to 110C; or 2. in a multi-stage procesJ:
2.i urea of for~ula IV
.NH2 ~ H2 (IV) is reacted wlth a diketon- of formula III

R3 - C - CH2 ~ C - R4 (III) in the presence of an acid in an inort solvent at te~porature~ of from 20C to 140C, preferably from 20C to 40C, and is cyclised to glve a pyrimldine co~pound of formula V

4jN- ~ (V) N=. ~ 4 and 2 2 the ON group in the resulting compound of formula V $s exchaDged for halogen by further reaction with excess POHal3,-in the pre~3ence or in the absence of a solvent, at temperatures of from 50C to 110C, preferably at the reflux tempersture of POHal3, to yield Hsl ~ . (VI) ~R4 Nal in the above formulae belng halogen, especlally chlor$ne or bromlne, and 2 3 the resultlng compount of $ormula VI ls reacted further wlth an anlline compound of formula VII

H2 ~ ~ (VII) ' R
, dependlng on th- reactlon condltlons eltber a) in th- pro-enc- of 8 proton acceptor, such a- an e~ce~- of the anlline ~ ;
compound of for ul- VII or an lnorganic b-se, wlth or wlthout ~olvent~
or b) in the pre~ence of an acld ln an lnert ~olvent, ln each ca~- at temperatureJ of from 60C to 120C, preferably from -~
80C to 100C or . .,: ~

~ '' ," " "'-'~' :. . -:

~~
9 ~33~759 3. in a two-stage procoss:
3.1 a guanidine salt of formula VIII

A (vIII?
NHz is cyclised with a diketone of formula III

R3 ~ - CH2 - C - R4 a) without solvents at temperatures of from 100C to 160C, preferably from 120C to 150C, or b) in an inert solvent at temperatures of from 30C to 140C, preferably from 60C to 120C, to give a pyrimidine compound of formula IX
~R3 HzN ~ ~- (IX) .~R4 and 3.2 the resulting compound of formula IX is reacted with a compound of formula X

in the pre~ence of a proton acceptor In aprotic solvent~ at temperatures of from 30C to 140C, preferably from 60C to 120C, to remove HY, the substituents Rl to R4 in formulae II to X bein8 aO defined for formula I, Ae being an acld anion and Y being halogen; or ., ~: - :. : ~.. :.

4. in a multl-stage process:
4.la~ thiourea of formula XI

S-C (XI) ~ Hz is raacted with a dlketone of formula III

R3 ~ - CHz - ~ - R4 (III) in the presence of an acid ln an inert solvent at temperatures of from 20C to 140C, preferably from 20C to 60C. and cyclised to give a pyrimidine compount of formula ~5~ XII) and the alkall metal or alksline esrth metal salt thereof l~ reacted wlth a co~pount of for~ula XIII

ZRs (XIII), whereln Rs i9 Cl-Czalkyl~ or benzyl that ls un~ubstltuted or substitutet ~ :
by halogen ant/or by Cl-C4alkyl and Z l~ halogen, to glve a pyrimidine compound of formula XIV
~R~ :
RsS~~ XIV) R ;~
4 . ~
or, b~ an i~othloronlum salt of formula XV

~,4C--SRs Ae (XV) ''.' ~ ..

:'. .
.''~

t ~3 1 759 i9 reacted wtth a diketone of formula III, preferably in a protic solvent, at temperatures of from 20C to 140C, preferably from 20C to 80C, and a pyrimidine compound of formula XIV i9 likewise obtained, and 4 2 the resultlng compount of formula XIV is oxitised with an oxidising agent, for example with a peracid, to g~ve the pyrimidino compound of formula XVI
N ~R3 RsSO2~ ~ ~ (XVI) ant 4 3 the resulting compound of formula XVI is reacted with 8 formylaniline of formuls XVII

~ ~ -NHCH0 (XVII) in an Inert solvent ln the presence of a basQ a- proton acceptor, at tQmperatures of from -30C to 120C, to glve a compound of for~ula XVIII

. (XVIII) and 4 4 the re~ultlng compound of formula XVIII 19 ~ub~ected to hydroly-ls in the presence of a base, for example an alkall metal hydroxlde, or of an acld, for example a hydrohallc acid or sulfurlc acld, ln water or aqueou~3 solvent mlxture~, such as aqueous alcohol~ or dlmethylformamlde, at temperature~ of from 10C to 110C, preferably from 30C to 60C, the substltuents Rl to R4 ln formulse XI to XVIII belng as defined for formula I and Ae belng an acid snlon snd Y belng halogen '': " ``: , : " :
';` ' : ' ~ . , :`` :
'~ ` ' : ' .`:
':'` .''- : :
~.,, ~, ~ : ' .

- ~ :

, ~3175q Compound~ of formula I in which R3 i~ the CH20H group ean be prepared by specisl proce~se~, a~ follow~:

Al.l the guanidlne salt of formula IIa Rl ~ ._. . NH2 NH C~ A (IIa) ~ NH~

or the gusnidine of formula IIb R~ . NH
NH ~ ~ ( IIb) .~R2 NH2 ls rescted with a ketone of for~ula XIX

(RcO) 2CH ~ -CH2~ -R4 (XIX) ~ ~
in whicb R6 ig cl-c4alkyl~ in a protic solvent or without solvents, at :~:
te~peraturos of from 40C to 160C, preferably fro~ 60C to 110C, to give a pyrimidine compound of formula XX

Rl ~ _ N~

2 R4 ;~:
and Al.2 tho re~ultlng acotal of f~rmula XX i~ hydroly~ed in the pre~once of an acit, for e~-mple hydrohalic acid or sulfuric acld, in water or aqueous solvent mlxtures, for example with solvonts such as alcohols or dimothylfor~amlde, at temperature~ of from 20C to 100C, preferably fro~
30C to 60aC, to glve the pyrl~idlnealdehyde of for~ula XXI
R~ ~CH0 ~--NH-- ~ ~- (XXI) -~

and ` ~ 33 1 759 Al 3 the re~ulting compound of formula XXI i9 hydrogenated with elemental hydrogen u~ing a catalyst or i8 reduced with a reducing agent, such as sodium borohydride, to give the correspondinF alcohol XXII

~---NH--~N ~ - (XXII);
~ 2 R~, or A2 1 the guanidine salt of formula IIa or the guanidine of formula IIb i9 reacted with a diketone of formula XXIII

R70Cl~z~--CHzl~--R4 (XXIII) in which R7 i~ benzyl that i9 un~ub~tituted or substituted by halogen or by Cl-C4alkyl, in a protic solvent or without solvents, at te~perature~
of from 40C to 160C, preferably from 60C to 110C, to give a pyrimidine compound of formula XXIV
R ~CN20R7 -NH- ~ ~ (XXIV) and in that compount A2 2 the CH20R~ ratic~ converted into a CH20H radlcal by hydrogena-tlon ln a olvent, preferably an aprotlc ~olvent, for example dioxane or tetrahydrofuran, w1th a catalyst, such a~ palladiu~-on-carbon, preferably Raney nlckol, at temp-rature~ of from 20C to 90C, preferably from 50C to 90C or ~ i A3 1 the guanidlne salt of formula IIa or the guanitlne of formula IIb 18 reacted w1th a diketone of formula XXV

~~C ~ ~V), 1 ~3 1 759 in which R8 19 Cl-C6~1kyl, C3-CGalkenyl or benzyl that i~ unsubstituted or ~ubstituted by halogen or by C1-C~alkyl, in a protic solvent or wlthout ~olvents, at temperatures of from 40C to 160DC, preferably from 60C to 110C, to give a pyrimidine compound XXVI
CH20Rg NH--~ ~- (XXVI) ~2 N=.~R4 and ;~

A3.2 wlth the resulting compound of formula XXVI an ether cleavage 19 carried out with a hydrohalic acid, preferably hydrobromic acid, or a :
Lewis acid, such a~ aluminium halide (for example AlCl3) or boron halide B(Hal)3 (for example BBr3 or BCl3), in sprotic solventq, for example hydrocarbons or halogenated hydrocarbon~, at temperatures of from -80C to 30C, preferably from -70C to 20C.

Compounds of formula I in whlch R3 i8 the CH2Hal group can be prepared by reacting a compound of formula XXII with phosphorus halide or thionyl halide ln the presence of tertiary bases, for exa~ple pyridine or :~
triethylamlne, in inert solvQnts, at temperature~ o$ from 0C to 110C, preferably from 0C to 80C.

Co~pound~ of formuls I in which R3 i~ the CH2F group can be pr~pared byreactlng a compound of f-ormuls XXVII
R~

ln which X i8 chlorine or bromine, with potassium fluoride, prcferably lyophilised potassium fluoride, in the presence of catslytic amounts of cesium fluoride or a Crown ether, for example 18-Crown-6-ether, in apro-tic solvents, such a~3 acetonitrile, at temperstures of from 50C to 160C
in a pre~sure autoclave.

t~3 ~ ~5~

A further process for the preparation of compounds of formula I in which Rl is the CH2F group consi~t~ in fluorinating a coMpound of formula XXII
with N,N-diethylaminosulfur trifluoride (- DAST) in aprotic solventQ, such a~ dichloromethane, chloroform, tetrahydrofuran or dio~ane, at temperatures of from 0C to 100C, preferably from 10C to 50~C

In the above formulae XVIII to XXVII too, R1, R2 and R4 are a~ defined for formula I

In the described proces~es, in compounds of formulae IIa and VIII the following salt radical~, for example, are suitable for the acid anion A~
carbonate, hydrogen carbonate, nitrate, halide, sulfate and hydrogen ~ulfate In the processes described above, in the compound of formula XV the following ~alts, for example, are suitable for the acid anion Ae halide, sulfate and hydrogen ~ulfate Halide in each ca~e i8 to be understood as meaning fluor$de, chloride, bromide or iodide, pre$erably bromide or chloride The acits u~et are e~pecially inorganlc acids, such as, for example, hydrohalic acids, for example hydrofluoric acid, hydrochloric acid or hydrobromic acid, and al~o sulfuric acid, phosphoric acid or nitric acid;
howe~er, sultable org-nic acids m-y also be used, such as, inter alia, acetlc acld and toluene~ulfonic acid As proton acceptor- there are used, for ex-mple, inorganic or organic bases, ~uch a~, for example, alkali meeal or al~aline earth metal compounds, for example the hydroxides, oxides or carbonates of lithium, sodium, potss~ium, magnesium, calciu~, strontium and barium, or also hydrides, such as, for example, sodium hydride As organic bases there may be mentioned, for example, tertiary amine3, such a~ triethylamine, trlethylenediamine, pyridine In the processes descrlbed above, for example, the following solvents may be used, tependent on the particular reaction conditions, in atdition to those alreaty mentionet s ;~

- 16 - ~ 33 1 7~9 Halogenated hydrocarbons, especially chlorinaeed hydrocarbons, such a~
tetrachloroethylene, tetrschloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, chloronaphthalene, carbon tetra-chloride, trichloroethane, trichloroethylene, pentachloroethane, di-fluorobenzene, 1,2-dichloroethane, l,l-dichloroethane, 1,2-cis-dichloro-ethylene, chloroben7ene, fluorobenzene, bromobenzene, dichlorobenzene, dibromoben~ene, chlorotoluene, trichlorotoluene; ethers, such as ethyl propyl ether, methyl tert.-butyl ether, n-butyl ethyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, diisopropyl ether, anisole, cyclohexyl methyl ether, diethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, thioanisole, dichlorodiethyl ether; nitrohydro-carbons, such as nitromethane, nitroethane, nitrobenzene, chloronitro~
benzene, o-nitrotoluene; nitriles, ~uch a~ acetonitrile, butyronitrile, isobutyronitrile, benzonitrile, m-chlorobenzonitrile; aliphatic or cyclo-aliphatic hydrocarbons, such as heptane, hexane, octane, nonane, cymol, petroleum fractions within a boiling point range of from 70C to 190C, cyclohexane, methylcyclohexane, decalin, petroleum ether, ligroin, tri-methylpentane, such as 2,3,3-trimethylpentane; esters, such as ethyl acetate, ethyl acetoacetate, isobutyl acetate; amides, for example formnmide, methylformamide, dlmethylformamide ketones, such a~ acetone, methyl ethyl ketone; alcohol-, especially lower aliphatic alcohols, such as, for example, methanol, ethanol, n-propanol, Isopropanol and the butanol isomers; and, where appropriate, al~o ~ater. Also suitable are mlxture- of the montloned solvents and diluents. ;~
. :~ .;
Method- of ~ynthesl~ that are analogous to the above-descrlbed prepara- -~tlon proce~se~ have boen publlshed in the literature.

As references there may bs mentionet:

Process 1: A. Kreutzberger and J. Glllessen, J. Heterocyclic Chem. 22, 101 (1985).
Proce~s 2:, Stage 2.1: O. Stark, Ber. Dtsch. Chem. Ges. 42, 699 (1909);
J. Hale, J. Am. Chem. Soc. 36, 104 (1914); G.M. gosolapoff, J. Org.
Chem. 26, 1895 (1961). Stage 2.2: St. Angerstein, Ber. Dtsch. Chem. ``
Ges. 34, 3956 (1901) G.~. Ro~olapoff, J. Org. Chem. 26, 1895 (1961~.

- - 17 - ~ 331 7r)~

Stage 2.3: M. P. V. Boarland and J. F. W. McOmie, J.
Chem. Soc. 1951, 1218; T. Mataukawa and K. Shirakuwa, J. Pharm.
Soc. Japan 71, 933 (1951); Chem. Abstr. 46, 4549 (1952).
Process 3: A. Combes and C. Combes, Bull. 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 all partial steps, form part of the present invention.
The following compounds, which are used as inter-mediates in the preparation of the compounds of formula I, arenovel. Compounds of formula XXX form the subject of this first divisional application. Compounds of ~formula XXI form the subject of the second divisional application.
1) Compounds of formula N
Ro ~ . XXX
_, in which: Ro is halogen or R5SO2; R3 is hydrogen; Cl-C4alkyl; or Cl-C4alkyl substituted by halogen, hydroxy and/or cyano; cyclo-propyl; or cyclopropyl mono- to tri-substituted by methyl and/or - by halogen; R4 is C3-C6cycloalkyl or C3-C6cycloalkyl mono- to tri-substituted by methyl and/or by halogen; and R5 is Cl-C6alkyl or benzyl that is unsubstituted or substituted by halogen and/or ~: -., . . - -,, ~ S ~ ~ 4 133175~

by Cl-C4alkyl. Chlorine and bromine are preferred as halogen substituent Ro.
2) Compounds of formula XXI

CHO

- NH ~ XXI -~
\, ~ ./ \N ~

R2 4 ' in which: Rl and R2 independently of one another are hydrogen, halogen, Cl-C3alkyl, Cl-C2haloalkyl, Cl-C3alkoxy or Cl-C3halo-alkoxy; and R4 is C3-C6cycloalkyl or C3-C6cycloalkyl 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 curati~e, preventive and, in particular, ~ystemic properties, and can be used for protecting numerous cultivated plants. With the compounds of formula I it is possible to inhibit or destroy the pests which occur in plants or ' in parts of plants (fruit, blossoms, leaves, stems, tubers, roots) in different crops of useful plants, while at the same time the parts of plants which grow later are also protected, for example, from attack by phytopathogenic microorganisms.
The compounds of formula I are effective, for example, ~-~ ' r~

- 18a - 1 ~3~7~

against the phytopathogenic fungi belonging to the following 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 compounds of formula I can also be used as dressing agents for protecting seeds (fruit, tubers, grains) and plant cuttings against fungus infections as well as against phytopathogenic fungi which 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 of the parent application 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 invention of the parent application further embraces the preparation of those compositions, which comprises homogeneously mixing the active ingredient with one or more compounds or groups of compounds described herein. The invention furthermore relatès to a method of treating plants, which comprises applying thereto the novel compounds of formula I or the novel compositions.

Target crops to be protected within the ~cope of the present invention compri~e e.g. the following species of plants:
cereals (wheat, barley, rye, oats, rice, maize, sorghum and related crops), beet (sugar beet and fodder beet), pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberrie~, raspberries and blackberries), leguminous plants (beans, lentil~, peas, soybean~), oil plantQ (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts), cucumber plants (cucumber, marrows, melons?, fibre plants (cotton, flax, hemp, jute), citrus fruit (oranges, lemons, grapefruit, mandarlns~, vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika), lauraceae (avocados, cinnamon, camphor), or plants such as tobacco, nuts, coffee, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamentals.

The compounds of formula I are normally applled in the form of composl-tlons ant 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 fertllisers or m$cronutrient donors or other prepara-tions that influence plant growth. They csn also be selective herbicides, insecticides, fungicide~, bactericides, nematicides, molluscicides or mixtures of several of the~e preparations, if dosired together with further carrier-, surfactants or application-promoting ad~uvants customar11y employed ln the art of formulation.

Suitable carri-r- and ad~uvants can be solid or liquid and correspond to the Jubstance~ ordinarily employed in formulation technology, e.g.
natural or regenerat0d olneral substances, ~olvents, dispersant~, wetting agents, tackifiers, thickeners, binders or fertilisers.

A preferred method of applying a compound of formula I, or an agro-chemical composition which contains at least on0 of said compoundJ, i9 foliar application. The number of applications and the rate of applica-tion depend on the risk of infestation by the corresponding pathogen.
However, the compounds of formula I can also penetrate the plant through the roots via the soil (syi~temic act~on) if the locu~ of the plant is impregnated with a liquid formulation, or if the compounds are applied in ' :, 1 ;~3 t 759 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 formuls I may, however, 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 ~olid formulation.

The compounds of formula I are used in unmodified form or, preferably, together with the ad~uvants 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 emul~ions, wettable powders, soluble powders, dusts, granulates, and also encapsulations in e.g.
poly~er substanc~s. AB with the nature of the composltions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordsnce with the intended ob~ectives and the prevailing circumstances. Advantageous rates of application are normally from 50 g to 5 kg of active ingredient (a.i.) per hectare, preferably from 100 g to 2 kg a.i./ha, most preferably from 200 g to 600 g a.i./ha.

The formulatlons, i.e. the compositions, preparations or mixtures contsining the compound (active ingredient) of formula I and, where appropriate, a solid or liguid ad~uvant, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredients wlth extenders, e.g. solvent!, solid carriers and, where spproprlate, surface-activ compound~ (surfactants~.

Suitable Jolvent~ are: aromatic hydrocarbonD, preferably the fractions containing 8 to 12 carbon atomJ, e.g. xylene mixtures or Jubstltuted naphthaleneJ, phthalate- such as dibutyl phthalate or dioctyl phthalate, aliphatic hydrocarbons such as cyclohexane or paraffins, alcohols and glycols and their ethers and esters, ~uch as ethanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones such a~
cyclohexanons, strongly polar solvent~, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, as well as vegetable oils or epoxidised vegetable oils, such as epoxidised coconut oil or soybesn oil;
or water.

j: ~ ~:

r ~ :

.~ 133175q The solid carrier~ used e.g. for dustq and dispersible powders are normally natural mineral fillers, such a~ calcite, talc~m, kaolin, montmorillonite or attapulgite. In order to improve the physical propertie~ it i~ also possible to add highly digpersed 8ilicic acid or highly dispersed absorbent polymers. Suitable granulated adsorptive carriers are porous types, for example pumice, broken brick, sepiolite or bentonite; and suitsble nonsorbent carriers are, for example, calcite or ~and. In addition, a great number of pregranulated ~aterials of inorganic nature can be used, e.g. especially dolomite or pulverised plant residues.

Particularly advantageous application-pro~oting adjuvants which are able to reduce substantially the rate of application are also natural (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 wetting properties.
Tho term "surfactants" will also be under~tood aJ comprising mixtures of surfactants.

Both so-callod water-Joluble oap~ and al~o water-soluble synthetic surface-active compound~ re suitable anionic surfsctants.

Suitabi- o-p~ ar- th- alkali metal ~alts, alkaline earth mHtal salts or unsubstitut-d or sub~tltuted a~monium salt~ of hlgher fatty acid~
(Clo-C~2), e.g. th- sod1u or potas~lum salts of ol-lc or ~tearlc acld or of natural fatty acld ~lxture~ whlch can b- obtalned e.g. from coconut oil or tallow oll. Mentlon may al~o be made of fatty acld methyllaurin salts .

More frequently, however, so-called ~ynthetic surfactants are used, espocially alkanesulfonates, fatty alcohol sulfates, sulfonated benzimidazole derivatives or alkylsulfonate~.

- ~ :

~ 33 i 759 The fatty alcohol sulfonates or ~ulfates are usually in the form of alkali metal qalts, alkaline earth metal qalts or unsubstituted or sub-stituted ammonium salt~ and contain a Cg-Cz2alkyl radical which alqo includes the alkyl moiety of acyl radicals, e.g. the sod~um or c~lcium salt of ligno~ulfonic acid, of dodecylsulfate or of a mixture of fatty alcohol qulfates obtained from natural fatty acids. These compounds also compriqe the ~alts of sulfated and ~ulfonated fatty alcohol/ethylene oxide adduct~. The sulfonated benzimidazole derivativeq preferably con-tain 2 qulfonic acid groups and one fatty acid radical containing 8 to 22 carbon atoms. Example~ of alkylarylsulfonate~ are the ~odium, calcium or triethanolamine salts of dodecylbenzenesulfonic acid, dibutylnaphtha-lenesulfonic acid, or of a condensate of naphthalenequlfonic acid and formaldehyde.

Also ~uitable are corresponding phosphates, e.g. salts of the phosphoric acid e~ter of an adduct of p-nonylphenol wlth 4 to 14 moles of ethylene oxide.

Non-ionic ~urfactant~ are preferably polyglycol ether derivative~ of allphatic or cyclosliphatlc slcohols, or ~aturated or unsaturated fatty acld~ and alkylphenols, sald derivativeJ containing 3 to 30 glycol ether groups and 8 to 20 carbon atoms ln the (aliphatic) hydrocarbon moiety and 6 to 18 carbon atom- in the alkyl molety of tho alkylphenol~.

Further suitabl- non-ionic surfaceants ar- the water-soluble adduct~ of polyethylen- oxid- wlth polypropylene glycol, ethylenediamlnopolypropy-len- glycol and alkylpolypropylene glycol containlng 1 to 10 carbon atoms in tho alkyl ch-ln, which adduct~ contain 20 to 250 ethylen- glycol ether groupJ nd 10 to 100 propyl-ne glycol ethor groups. The~e compound usually contain 1 to 5 ethylene glycol unlts per propylene glycol unit.

Representatlve example~ of non-ionic surfactants ar- nonylphenolpoly-ethoxyethanols, castor oll polyglycol ethers, polypropylene/polyethylene oxlde adduct~, trlbutylphenoxypolyethyleneethanol, polyethylene glycol and octylphenoxypolyethoxyethsnol.

Fatty acid esterR of polyoxyethylene sorbitan, e.g. polyoxyethylene sorbitan trloleate, are al~o su1table non-lonlc ~urfactants.

';; ' ' : -~: ;:. . , : . ~ :: :: -: ::: ~, :

~ - 23 - 1 3 31 7~

Cationic surfactants are preferably quaternary ammonium salts which contain, as N-substituent, at least one C8-C22alkyl radical and, as further substituents, unsubstituted or halogenated lower alkyl, benzyl or hydroxy-lower alkyl radicals.
The salts are preferably in the form of halides, methylsulfates or ethylsulfates, e.g. stearyltrimethylammonium chloride or benzyldi(2-chloroethyl)ammonium bromide.
Further surfactants customarily employed in the art of formulation are known to the person skilled in the art or can be taken from the relevant specialist literature.
The agrochemical compositions usually contain 0.1 to 99 ~i, 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 commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations. -The compositions may also contain further auxiliaries such as stabilisers, antifoams, viscosity regulators, binders, tackifiers as well as fertilisers or other active ingredients for obtaining special effects.
The following Examples serve to illustrate the inventions of the parent and both divisional applications in greater detail, without limiting it.
1. Preparation EXamples Example 1.1: Preparatian af 2-phenylamino-4-methyl-6-cyclopropyl-- pyrimidine 1 3 3 1 7 5 q N. ,/
NH~ [Comp. No. 1.1]
,--. N=\
j~, ` ' !`, ': ~ ' ' ' , ~ 1 33 1 759 10 g t51 mmol~ of phenylguanidine hydrogen carbonate and 9 7 g (77 mmol) of l-cyclopropyl-1,3-butsnedione are heated at 110C for 6 hours with stirring, the evolutlon of csrbon tioxlde whlch occurs subsidlng a~ the reaction progresses After the dark brown emulsion has been cooled to room temperature, S0 ml of diethyl ether are added and the mixture is washed twice with 20 ml of water each time, dried over sodium sulfate and filtered, and the ~olvent i9 evaporated The dark brown oil whlch remains (~ 13 1 g) i9 purified by column chromatography over silica gel ~diethyl ether/toluene 5/3) After the eluant mixture has been evaporated off, the brown oil i9 made to crystallise and recrystallised from diethyl ether/petroleum ether at 30-50C Light-brown crystals are obtained Meltlng point 67-69C; yield 8 55 g (38 mmol) (~ 74 5 X of the theoretical yield) Example 1 2 Preparation of 2-anilino-4-formyldiethyl-acetal-6-cyclo-propylpyrimidine ~CH(Oc2Hs ) 2 ---NH--~
=- N=-~

_ ~ . J ~ i ' 11 7 g (59 2 mmol) of ph-nylguanldine hydrogen carbonate and 13 3 g (62 2 mmol) of 1-cyclopropyl-3-for yldlethylacetal-1,3-propanedlone ln 40 ml of ethanol are h sted unter reflux for 5 hour~ wlth ~tirrlng, the evolutlon of carbon dloxlde sub~ldlng as the reactlon progr-~e~ After the dark brown e ul~ion ha~ be-n cooled to room temperature, 80 ml of dlethyl th-r ar- added and the ml~ture 1- washed twlce wlth 30 1 of water each tlme, drlod over sodlum aulfQt- and flltered, and the solvent 1J vaporated Th- dark brown oll whlch r-maln~ (17 g) 1~ purlfled by column chromatography over sllica gel (toluene/ethyl acetate 5/2) After the eluant mlxture hà~ been evaporated off, a reddl3h brown oil remains ~ -~
whlch h-- a refractlve lndex nDS 1 5815 Yleld 15 8 (48 mmol; 81 1 %
of th~ theoretlcal yleld) : :

' :

~ 33 1 759 E~ample 1.3: Preparation of 2-anilino-4-formyl-6-cyclo-propylpyrimidi~e ~CH0 ._. N--- (Comp. no. 2.1?
= . _--_--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 50C for 14 hours with vigorous stirring ant, 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 % ~odium hydroxide solution. The ethyl acetate solution iJ then separated off, dried over sodlum sulfate and filtered, and the solvent 19 evaporated. For purification, the brownish solid i9 re-crystallised from 20 ml of isopropanol in the presence of active carbon.
The yellowish crystal~ melt at 112-114C. Yield: 7.9 g (33 mmol; 84 % of the theoretical yield).
xample 1.4: Preparation of 2-anilino-4-hydroxymethyl-6-cyclopropyl-pyrimidina ~CHzOH
~ ~--NN~ - (Cnmp. no. 1.48) . _ .
. . .
a~ 2.3 g (60 maol) of aodium borohydride are added in portion~ at roo~
temperature, within a period of 15 minutes, with stirring, to 14.1 g (59 amol~ of 2-anllino-4-formyl-6-cyclopropylpyrimidine in 350 ml of absolute methanol, whereupon the reaction mixture warDs up to 28C with evolution of hydrogen. After 4 hours the mixture i~ acidlfied by the dropwiAe addi-tion of 10 ml of concentrated hydrochloric acid, 120 ml of 10 % sod~um hydrogen carbonate solution are added dropwise, ant the ~ixture is then diluted with 250 ml of water. The resulting prscipitate is filtered off, dried, largely ti~solved in 600 ml of diethyl ether at elevated teapera-ture, treated with active carbon and filtered. The clear filtrate is f~
3 t 7 5 9 concentrated until it becomes turbid and i~ then diluted with petroleum ether, and the light-yellow crystalline powder is filtered off;
m p 123-125C Yield 10 8 g (44 8 mmol 75 9 % of the theoretical yield~

b) 5 9 g (23 mmol) of 2- nilino-4-methoxymethyl-6-cyclopropylpyrimidine, prepared from phenylguanidine and l-cyclopropyl-4-methoxy-1,3-butane-dione, are dissolved in 200 ml of dichloromethane snd the solution i9 cooled to -68C 6 8 g (27 mmol~ of boron tribromide are ~lowly added dropwise to the salmon-coloured ~olutlon within a period of half an hour, with vigorous stirring, and the cooling bath i9 then removed and stirring i8 continued for a further 2 hours st room temperature After the addi-tion of 150 g of ice-wster, the precipitat-d crude product i9 filtered -off and recrystalli~ed from methanol using actlve carbon The light-yellow crystal~ melt at 124-126C Yield 4 7 g (19 5 mmol; 84 7 70 of the theoretical yield) E~ample 1 5 Pre ~ -phenylamino-4-bromomethyl-6-cy-clopr ~yrimidine , ~
~CHzBr ~f ~ -NN~ (Comp no 1 4) ~ . .
!' :

15 6 g (75 m-ol) of thionyl bromide in 50 ml of di-thyl ether are add-d tropwi-- wlthin a p-riod of half an hour, wlth ~tirring, to 12 g (50 mmol) of 2-ph-nylamlno-4-hydro~ymethyl-6-cyclopropylpyrimidine and 0 4 g (50 m ol) of pyridine in 350 ml of di-thyl ether Aft-r ~tirrlng -~
for 2 hourJ at room temperature, a further 0 4 g (50 mmol) of pyridine are added and the mixture i9 heated und-r reflux for S hour~ After cool-ing to room temperature, 200 ml of wster ar- added snd th- pH i9 ad~uited to 7 by the dropwi-e addition of 140 ml of ~atur-ted sodium hydrog-n carbonate solution The diethyl ether pha~- i9 s-psrated off and th-n washed twic- with 100 ml of water ach tim-, dried over sodium aulfate and filt-red, and the solvent is evaporated The brown oil which remains i9 purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether ~b p 50-70C) 5/3/1/1). After the eluant mixture has been e~aporated off, the yellow oil i8 diluted with diethyl ether/petroleum ether (b.p. 50-70DC) and crystallised at reduced temperature. The yellow crystalline powder melts at 77.5-79.5C. Yield: 9.7 g (32 mmol; 64 % of the theoretical yield).

Example 1.6: Preparation of 2-phenylamino-4-fluoromethyl-6-cyclopropyl-pyrimidine ~CHzP
~ NH-- ~ ~ (Comp. no. 1.59~
_.

a) 3.9 g ~12.8 mmol) of 2-phenylamino-4-bromomethyl-6-cyclopropylpyrimi-dine, I.S g (26 mmol) of spray-dried potas~ium fluoride and 0.3 g (1.13 mmol) of 18-Crown-6-other are heated under reflux for 40 hours in 50 ml of acetonitrile. A further 0.75 g (13 mmol) of potassium fluoride i~ then added and the mixture i~ heated for 22 hours. To complete the reaction, a further 0.7S g (13 mmol) of ~pray-dried potassium fluoride and 0.1 g (0.38 mmol) of 18-Crown-6-ether are added and the mixture i8 heated under reflux for a further 24 hours. After the Juspension haJ been cooled to room temperature, lS0 ml of diethyl ether are added and the mixture i9 washed three tlmes with 20 ml of water each time, dried over sodium sulfate and filtered, and the Jolvent i~ evaporated. Thc brown oil which remain~ i9 purifi-d by column chrooatography over Jillca gel (toluene/chloroform/di-thyl ether/petroleum eth-r (b.p. 50-70C):
5/3/1/1). After the lu-nt mixture ha~ been evaporated off, th- yellow oil iSI dilutsad with 10 ml of petroleum ether (b.p. 50-70C~ and cryJtalli-ed t reduc-d temperature. Th- yellow cryJtalJ melt at 48-52C;
yield: 2.1 g (8.6 mmol); 67.5 % of the theoretical yleld.

b) 6.1 g (37.8 mmol) of diethylaminoJulfur trifluoride in 15 ml of di-chloromethane are 910wly added dropwise within a p-riod of on- hour, with ~tirring, to a suspenJion of 9.1 g (37.8 mmol) of 2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimidine in 80 ml of dichloromethane. After the addition of S0 ml of ice-water~ 50 ml of 10 s~ aqueous3 Jodium hydrogen carbonate solution are added dropwise. When the evolution of carbon dioxide haJ ceas3ed, the organic phase i9 ~eparated off and the aqueouJ

: ` .

t ~3 1 ~59 phaqe i8 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 Qolvent is evaporated. The black oil which remainB i9 purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50-70);
5/311/1). After the eluant mixture haQ been evaporated off, the yellow oil is diluted with 20 ml of petroleum ether (b.p. 50-70C) ant cry~tallised at reduced temperature. The yellowish crystal~ melt at 50-52C. Yield: 4.9 g (20.1 mmol; 53 % of the theoretical yielt).

Example 1.7- Preparation of 2-hydroxy-4-methyl-6-cyclo-propylpyrimidine ~CH3 H0~
=. .
._. :

15 ml of concentrated hydrochlorlc acid are added at roqm temperature to 6 g (100 m~ol) of urea and 12.6 g (100 mmol) of 1-cyclopropyl-1,3-butane-dlone in 35 ml of ethanol. Afeer the mlxture has ~tood for 10 days at roo~ temperature, it i~ concentrated in a rotary evaporator at a bath temperature not exc-eding 45C. The residue i9 dissolved in 20 ml of ethanol, the hydrochloride of the reactlon product precipitating after a -~
short time. 20 ml of diethyl ether are added with Jtirring, and the precipitated whit- cry-tal~ are filtered off, washed with an ethanol/di-thyl eth-r mixture and drled. Concentration of the flltrate and recry-talli~-tion fro~ an ethanol/diethyl ether mlxture: 1/2 yield a further quantity of hydrochloride. The whlte cryJtals melt > 230C.
Yleld: hydrochlorld- 12.6 g (67.5 mmol; 67.S % of the theoretical yield).
, Example 1.8: Preparation of 2-chloro-4-methyl-6-cyclo-propylpyrimidine ~CH3 Cl~ (Comp. no. 3.1) `I~- `
~ ~

52.8 g (0.24 mol) of 2-hydroxy-4-methyl-6-cyclopropylpyrimldine hydroc-hloride are introduced at room temperature, with stirring, into a mixture of 100 ml (1.1 mol) of phosphorus oxychloride and 117 g (0.79 mol) of diethylaniline, the temperature rising to 63C. 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 phaiqe is separated off and washed with saturated aqueous sodium hydrogen carbonate solution until neutral. Removal of the solvent by evaporation yieldq 116.4 g of oil, which i3- composed of the reaction product and diethylaniline. Separation of the diethylaniline and purifi-cation of the crude reaction product are effected by coluwn chromato-graphy over silica gel (hexane/diethyl acetate: 3/1). The colourless oil which crystallises after several days hai3 a refracti~e index nDS:
1.5419; yield: 35.7 g ~0.21 mol; 87.5 % of the theoretical yield);
melting point: 33-34C.

Example 1.9: Prepsration of 2-(m-fluorophenylamino)-4-methyl-6-cyclo-propylpyrimidine ~CH3 NH~ Comp. no. 1.63) !' A solution of 5.5 g (50 mmol) of 3-fluoroanlline and 9.3 g (55 m~ol) of2-chloro-4-oethyl-6-cyclopropylpyrlmidine in 100 ml of othanol iJ
at~u~ted to pH 1 with 5 ml of concentrated hydrochloric acid, with stirr-ing, and is th-n he-t-d under reflux for 18 hour~. After the brown emul-sion has been cooled to room temperature, lt is rendered alkaline with 10 ml of 30 % awmonia, poured onto 100 ml of ice-water and extracted twice with 150 ml of diethyl ether each time. The combined extracts ara washed with 50 ml of water, dried over sodium sulfate and filtered, and th- solvent is evaporated. The yellowish crystal~ which remain are puri-fied by recrystalli~ation from diisopropyl ether/petroleum ether (b.p. 50-70C). The white crystals melt at 87-89C; yield: ô.3 g (34 m~ol; 68 % of the theoretical yield).

~ 33 1 75~

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

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In Tables 2, 3 and 4 intermediate products, according to the inventions of the divisional applications are exemplified.

Table 2: Compounds of the for~uld R~ b ~CHO
~ NH--~ ~

Comp. 21 R2 Physical .
no. _ . Constsnt . ~.
2.1 H N -.~¦ m.p. 112-114UC
~Cl 2.2 N H --~!~CH3 m.p. 123-127C

2.3 H H -.~¦ m.p. 87-90C

2.4 4-Cl H ~ : -. ~F
2.5 H H -.~¦ m.p. 128-132C

2.6 3-F N --~

2 7 b-F H \ I .

.j ~

' .

" ~' ' " ~;, 13317~'~

Table 3: ~R3 Comp. Hal R3 R4 Phy-lcal :~o . con8tant 3.1 Cl -CH3 ~ ~cH3 m.p. 33-34C

3.2 Cl -CH3 ~ nD5. 1.5432 3.3 Cl -CH3 _ ~ ~.

3.4 Cl -CH3 --~!
. /-~
3.5 Cl -CH3 _.

3.6 Cl -C3~7-i -.~1 3. 7 Cl ~-~I-CCH3 c33 3.8 Cl -CH2 H-CH3 --~!~cH3 3.9 Cl _.~j _.~j . ~CH3 .
3 .1 0 Br -CH3 -.~¦ ... _ .' '.'"''''~'~ ',, ` ` 1 33 1 759 Table 3: Continuation Comp. Hal R3 R4Physical no _ constant 3.11 Cl H -'~! :

3.12 Cl -C4Hg-n ~-~! .

3.13 Cl -CHC12 --~!

3.14 Cl -CN3 _C~r 3.15 Cl -CH3 --~!
~Cl .
3.16 Cl -CH3 --~i~CH3 3.17 Cl -C2Hs -.~¦ m.p. 32-35C

3.18 Cl -CF2CF3 --~

:

r ~_ 1331759 Table 3: Continuation Comp. 3al R3 R4l Phy~3ical no. constant _ 3.21 Cl -C2Hs --~3! ~P 28-31C

3.22 Cl -CH3 ~-f~!

3.23 Cl -C4Hg-~3ek. --~¦

3.24 Cl -CH3 ~F m.p. 42-45C
3.25 I Cl ~ f~3~

3.26 Cl -CHJ ~ Br . fH.3 3.27 Cl -CH3 ~-~!~Cl . ~CH3 ~CH3 3.28 Cl --~! --~

3.29 Br -CH3 _.~j :
~Cl 3 30 br -CH3 ~ ~ :

'` `''~"' ' ;''-' / -1.~31759 Table 3: Continuation I Comp. Nal R3 R4 Physical no. I constant 3.31 Cl -C3H7-n --~!

3.32 Cl -CH3 ~ .
~CH3 .
3.33 Br -CZHs ~

3.34 Cl -CF3 _.~¦

3.35 Br -C2Hs ~Cl 3.36 Cl -CH3 -.~¦

¦ 3-37 ¦ l l i 3.38 Cl -CH3 --~!~CH3 3.39 Cl -CCl~z -.

3.40 Cl --~1 ~-~

3.41 Cl -CH3Cl --~

~ 3.42 Cl -CH2F --~

`~ 3.43 Br --~! -~!

3.44 Br -CH2F -.~¦

3 43 Cl -CHzOH -.~¦

1 33 1 i5~

Comp . Hal R3 R4 Physical no . const~nt 3. 46 ~r --CHzOH ~

' '; ~ ' ~`

:: :

i.:. .:: : ~:

,:::~: .::
: ~ :: ::

:. .~

1 33 ~ 759 Table 4: N--~

RsSOz~~

Co p. Rs ___ __ Physical .. _. __ _._ 4.1 CH3 -CH3 _.~¦

4.2 CH3 -CH3 .~ ~.

4.3 C4Hg-n -CH3 ~!

4.4 CH3 -CH3 --~

4.5 CH2--~ ~. -CH3 ~ r 4.6 CH3 -CH

4.7 -CH~ --CH3 -CH3 ~!

4.8 C2H5 -CH3 _.~j ~Cl 4.9 CH3 -CH3~cH3 ~ cH3 4 10 CH3 ~ -.~¦ m.p. 84-89C

: ,:

- 6~ - 133~759 Table 4: Continuation Comp. Rs R~ R4Physical no. con~tant 4.11 CH2~ --Cl -CH3 _.~j .=. ~CH3 4.12 CH3 -CH~ -.~¦

4.13 CH~ -CH~ _~j ~F
4.14 CNJ -CH3 --~; Cl 4.15 C2Hs -CH3 --~!

4.16 CN~ -C2Hs _.~; m.p. 64-68C

4.17 C~Hs -CH3 -.~¦ ~' 4.18 C~H7-n - -CH3 _.~j fH;
4.19 CH3 -CH3 -.~¦
~CH3 ~ ~
4.20 C3H7-n -CH3 ~ ~ ~ -e.. ' ::

- 69 - ~3317~'~

Table 4: Continuation Comp. Rs R3 R~ Phy3ical no. constant . ~F

4.21 CH~ -CH3 ~i ~F
4.22 CJH7-n -CH3 ~F

. -4.23 CH3 -CH3 ~i . ~CH
4.24 CHj -C2Hs -.~¦
~Cl 4.25 CH3 -CH3 ~CH3 4.26 C2Hs -CH3 --~3~CI

4.27 CH3 -CH3 -.~¦ Cl ~CH3 4.28 CR~ -CH3 --~i~CH3 4.29~ CH~ ~i --~j ~-P. 54-58C
~Cl 4.30 C3H7-n -C3~ ~

~;:

_ 70 _ 1 33 1 759 2. Formulation Example~ for liguid active ingredients of formuls I
(throughout, percentageQ are by weight) 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 moles of ethylene oxide) 5 %
tributylphenol polyethylene glycol ether (30 moles of ethylene oxide) - 12 X 4 X
cyclohexanone - 15 % 20 %
xylene mixture 65 % 25 % 20 X

Emulsions of any desired concentration can be produced from such concentrates by dilution with water.

2.2. Solutlons a) b) c) d~
a compound of Table 1 80 X 10 X 5 % 95 %
ethylene glycol monomethyl ether 20 X
polyethylene glycol (mol. wt. 400) - 70 % - -N-methyl-2-pyrrolidon- - 20 X
epo~ldised coconut oll - - 1 % 5 X
petroleum fraction (boiling range 160-190C) - - 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 acid1 %
attapulglte - 90 %

t 33 ~ 759 The active ingredient i9 dissolved in methylene chlorite, the solution i9 sprayed onto the carrier, and the solvent i~ subaequently evaporated off in vacuo.

2.4. Du~ts a) b) a compound of T~ble 1 2 % 5 %
highly dispersed ~iliclc acid 1 % 5 %
talcum 97 %
kaolin - 90 %

Ready-for-use dusts are obtained by intimately mixing the carrier~ withthe active ingredient. , Formulation Examples for solid active ingredients of formula I (through-out, percenta~es are by weight) 2.5. Wettable powders a) b) c) a compound of Table 1 25 X 50 %75 X
sodium lignosulfonate S X 5 %
sodium laurylsulfate 3 % - 5 Z
sodium dilsobutylnaphthalene-sulfonate - 6 %10 X
octylphenol polyethylene glycol ether (7-8 mole~ of thylene oxide) - 2 %
highly disp-rsed slllcic acid 5 % 10 % 10 %
kaolin 62 % 27 %

The active ingredient i9 thoroughly mixed with the ad~uvants and the mixture is thoroughly ground in 8 suitable mill, affording wettable powders which can be diluted wlth 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 - 1 3 3 ~ 7 5 ~J

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 obtalned from this concen-trate by dllution with water. --2.7. Dusts a) b) a compound of Table 1 5 % 8 %
talcum 95 %
kaolin - 92 X

Ready-for-use dusts are obtained by mix~ng the active ingredient with the carrier and grinding the mixture in a suitsble mill.
:
2.8. Extruter granulate a compound of Table 1 10 %
90tium llgnosulfonate 2 %
carboxymethylcellulose 1 %
kaolin 87 X . ~-The actlve lngredlent 1- mixed and ground with the adJuvants, and the mlxture i~ ~ubsequently molstened with water. The mixture i8 extruded and then dried ln 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 miYer, to the kaolin moistened with polyethylene glycol. Non-du ty coated grsnu-lates are obtained in this manner.

_ 73 _ 1331759 2.10. Suspension concentrate a compound of Table 1 40 %
ethylene glycol 10 %
nonylphenol polyethylene glycol ether (15 moles of ethylene oxide) 6 %
sodium llgno~ulfonate 10 %
carboxymethylcellulose 1 %
37 % aqueous formaldehyde solutlon 0.2 %
~ilicone oil in the form of a 75 X
aqueous emulsion 0.8 %
water 32 X

The finely ground active ingrodient i9 intimstely mixed with the ad~u-vants, giving a suspension concentrate from which su~pensions of any desired concentration can be obtained by dilution with water.

3. Biological Examples Example 3.1: Action against Venturia inaequalis on apple shoots Residual protectiv- action Apple cuttlngs with 10-20 cm long fresh shoots are sprayed with a spray mixture (0.006 % active ingredient~ prepared from a wettable powder for-mulation of the test compound. The treated plant~ re infected 24 hours later with a conidia ~uspension of the fungus. The plants are then incu-bated for 5 day~ at 9O-100 % relative hu~idity and stood in a greenhouse for a further 10 days at 20-24C. Scab infestation is evaluated 15 dsy~
after inf-ction.

Compounds of Table 1 exhibit good activlty 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 hsnd, Venturia attack is 100 % in untreated and infected control plants.

~ ,, ~ .. ~ .. . ....... . . . .

-- 74 _ Example 3.2: Action against Botrytis cinerea on apples Residual protective action Artificially damaged apples are treated by the dropwlse appllcatlon tD
the damaged sltes of a spray mlxture (0.002 % active ingredlent) prepared from a wettable powder formulatlon of the test compound. The treated frults are then inoculated wlth a spore suspension of the fungus and incubated for one week at hlgh humidity and about ZOC. Evaluation is made by counting the rotted damaged sites an~ deriving tho funglcidal actlvlty of the test compound therefrom.

Compounds of Table 1 exhibit good actlvlty against Botrytls (less than -20 2~ attack~. Thus e.g. coopounds no~. l.I, 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 Botrytls attack to 0 to 10 %. On the other hand, Botrytls attack 19 100 X on untreated and lnf-cted control plant3.

Exsmple 3.3: Action against Erysiphe graminis on barley Residual protective actlon Barley p1ants about ô cn in height are sprayed wlth a spray mlxture (0.006 X active lngredlent) prepared from a wettable powder formulatlon of the test compound. The treated plantJ are dusted wlth conldla of the fungu~ after 3 to 4 hour~. The lnfected barley plant~ are ~tood ln a greenhouse at about 22C. The fungu- attaclc is evaluated after 10 day-.

Compound- of Tabl~ chlblt good actlvlty agalnst Eryslphe (le~s than 20 % att-clc). Thu- e.g. compounds nos. 1.1, 1.6, 1.13, 1.14, 1.35, 1.48, l.S9, 1.66, 1.69, 1.ô4, 1.ô7, 1.94, 1.10ô, 1.131, 1.158 and 1.236 reduce Erysiphe attack to 0 to 10 %. On the other hand, Erysiphe attack ls 100 X
on untreated and lnfected control plants.
, . , Example 3.4: Actlon agalnst Helmlnthosporlum gramlneum Wheat gralns are contamlnated wlth a spore suspenslon of the fungus and drled. The contamlnated gralns are dressed with a suspenslon of the test compound prepsred from a wettable powder (600 pp- of active ingredient, based on the weight of the seeds). Two days later the grains ar~ placed 7~ l 3 3 l 7 5 9 in suitable agar dishes and the development of fungus colonies around the grains is asseqsed after another 4 days. The effectiveness of the test COmpOUlld8 i9 evaluated on the ba~is of the number and sl7e o the colonies. The compounds of the Table substantially prevent fungus attack (0 to 10 %).

Example 3.5: Action against Colletotrichum lagenarlum on cucumbers After a cultivation periot of two weeks, cuçumber plants are sprayed with a spray mixture (concentration 0.002 %) prepared from a wettable powder formulation of the test compound. After two days the plants are infected with a spore ~uspension (1.5 x 105 spores/ml) of the fungus and incubatet for 36 hours at 23C and high humitity. Incubation is then continued at normal humidity and about 22-23C. Evaluation of fungus attack 19 made 8 days after infection. Fungus attack i9 100 Z on untreated and infected control plants.

Compounds of Table 1 exhibit good activlty and inhibit the spread of the disease. Fungus attack i9 reduced to 20 % or less.
xample 3.6: a) Contact action against Nephotettix cincticeps and Nila-parvata lugens (nymphs) The test is carried out with growing rice plant-. For this purpose 4 plants (14-20 day~ old) about 15 cm in height are planted into each of a number of potJ (dlameter 5.5 cm~.

The plantJ are sprayed on a rotary table with 100 ml of an aqueous emul-sion preparation containing 400 ppm of the te3t compound. After the spray coating has dried, each plant is populated with 20 ny~phs of the test organisms in the third stage. To prevent the cicadas from escaping, a glass cylinder which i9 open at both end~ i9 slipped over each of the plants and sealed with a gauze top. The nymphs are kept on the treated plants for 6 days until they have reached the adult stage. An evaluation i9 made on the basis of percentage mortality 6 days after population of the plants. The test is carried out at about 27C and 60 % relative humi-dity. The plants are exposed to light for a perlod of 16 hours per day.

1`~31759 b) Systemlc action against Nilaparvata lugens (in water) Rlce plants about 10 days olt (about 10 cm high) are placed in a plastics beaker which contains 150 ml of an aqueous emulsion preparation of the te~t compound in a concentration of 100 ppm and is closed by a perforated plastics lid. The root~ of each of the rlce plants are pushed through a hole in the pla~tlcJ lid into the aqueous test preparation. Then the rlce plants are populated with 20 nymph~ of Nilaparvata lugenJ in tho N2 to N3 stage and covered with a plastics cylinder. The teJt 19 carried out at about 26C and 60 % relatlve humidity, and the plants are expo~ed to llght for a period of 16 hours per day. After five day~ the number of ~ -dead test organisms is asJesJed in comparison with untreated controlJ. It i8 thus eJtablished whether the test substance ab~orbed via the root~
kills the test organisms at the upper part~ of the plants.

Compound3 of Table 1 exhibit a pronouncet kllllng action on the rice pests both in test a~ and in test b~. The mortality rate is 80 % or above. Almost total mortality (98-100 %) was achi-ved with compound noJ. 1.1, 1.6, 1.14, 1.59, 1.66, 1.87, 1.94, 1.108 and 1.236.

Claims (5)

1. A compound of the formula XXX
in which: R0 is halogen or R5-SO2-; R3 is hydrogen; C1-C4alkyl;
or C1-C4alkyl substituted by halogen, hydroxy or by cyano;
cyclopropyl; or cyclopropyl mono- to tri-substituted by methyl or by halogen; R4 is C3-C6cycloalkyl or C3-C6cycloalkyl mono- to tri-substituted by methyl or by halogen; and R5 is C1-C8alkyl or benzyl that is unsubstituted or substituted by halogen or by C1-C4alkyl.

2. A compound according to claim 1 wherein R0 represents bromine or chlorine, R3 represents hydrogen, methyl, ethyl, isopropyl, cyclopropyl, isobutyl, sec-butyl, methylcyclopropyl, hydroxymethyl, chloromethyl, fluoromethyl, dichloromethyl, trifluoromethyl, chlorodifluoromethyl or pentafluoroethyl, R4 represents cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, dimethylcyclopropyl, bromocyclopropyl, chlorocyclopropyl, fluorocyclopropyl, dichlorocyclopropyl, difluoro-cyclopropyl, bromochlorocyclopropyl, chlorofluorocyclopropyl or dichloro-methylcyclopropyl.

3. A compound according to claim 1 wherein R0 represents bromine or chlorine, R3 represents methyl, ethyl or cyclopropyl, and R4 represents cyclopropyl, methylcyclopropyl or fluorocyclopropyl.

4. 2-Chloro-4-methyl-6-cyclopropylpyrimidine.

5. 2-Bromo-4-methyl-6-cyclopropylpyrimidine.