CA1329934C - Pyrimidinealdehydes useful in the preparation of pesticides - Google Patents

Abstract

ABSTRACT
A compound of formula XXI

Description

32 9q3~ 21489-7555E

This application is a second divisional application of application No. 578,360 filed on September 26th, 1988. This application relates to compounds of formula XXI as deflned below.
A first divisional application relates to compounds of formula XXX 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 ~ormula I are defined as follows:

NH ~

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 halogen, hydroxy and/or cyano; cyclopropyl; or cyclopropyl mono- to tri-substituted by methyl and/or by'halogen; a~d ~4 is ~3-C6cycloalkyl or ~3~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 mean-ing, 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, CEIC12, CH2F, CC13, CH2Cl, CHF2, CF3, OEI2CH2Br, C2C15, CH2Br, CHBrCl etc., preferably CF3. Depending on the number of carbon atoms indicated, cyclo-alkyl 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 Specification 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 between the compounds of formula I and the known compounds is that at least one cyclo-alkyl radical and other suhstituents 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 32~9~4 The compounds of formula I are oils, resins or solids that are stable at room temperature and that are distinguished by valuabl~ microbicidal properties. They can be used preventively 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 salts 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, tri-chloroacetic acid, propionic acid, glycolic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid, oxalic acid, formic acid, benzenesulfonic 1 32993~

acid, p-toluenesulfonic acid, methanesulfonic acid, ~alicylic acid, p-aminosalicylic acid, 2-phenoxybenzoic acid, 2-aceto~ybenzoic acid or 1,2-naphthalenedisulfonic acld.

Metal ~alt complexes of formula I consist of the organic ~olecule on which they are based and an inorgsnic or organic metal salt, for example the halides, nitrates, sulfates, pho~phates, acetates, trifluoroscetat2~3, trichloroacetates, propionates, tartrates, sulfonates, salicylates, benzoates etc. of the elements of ehe 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. Tha metal~ can be in any of thelr various valencie~. Ihe metal complexes can be mono- or poly-nuclear, that is to say they can contain one or mora organic molecu-lar moieties as ligands.

An importnnt group of phytofungicides and insecticides i8 formed by those of formula I in which R1 and R2 are hydrogen.

A sp~cial group i9 for~ed by the following compound3 of formula I in which:
Rl and R2 independently of one another are hydrogen, halogen, C~-C3alkyl, C~-C2haloalkyl, C~-C3alkoxy or Cl-C3haloalkoxy; R~ is hydrogen, C~-C4alkyl or Cl-C4alkyl ~ubstituted by hslogen or by cyano; and R4 ls C3-C6cycloa1kyl or C3-C6cycloslkyl ~ub~ti-tuted by mnthyl or by halogen Thn following group~ of active ingredisnts are preferrad bacause of their pronounced ~icroblcidal, especially phytofungicidsl, activlty:

Group la: CompQunds of formula I in whlch:

Rl and R2 independently of one another are hydrogen, fluorine, chlorine, bromine, methyl, ethyl, halomethyl, methoxy, ethoxy or halomethoxy; R3 is hydrogen, methyl, methyl substituted by fluorineJ chlorine, bro~ine or by ,;
' ' ' :' : ' : ` :

'~ ~

cyano ethyl, ethyl substituted by fluorine, chlorine, bromine or by cylno; n-propyl or sec.-butyl; and R4 is C3-C6cycloalkyl or C3-C6cyclo-alkyl substituted by methyl, fluorine, chlorine or by bromine.

Of the above-mentioned compounds, an especially preferred group i9 formed by those in which Rl a R~ ~ hydrogen ~- Group laa~.

Group lb: Compound~ of formula I in which:

Rl and R2 independently of one another are hydrogen, chlorine, bromine, methyl, ethyl, trifluoromethyl9 methoxy, ethoxy or difluorome~hoxy; R3 i9 hydrogen, methyl, methyl substituted by fluorine, chlorine or by cyano, ethyl or n-propyl; and R4 i8 C3-Cscycloalkyl or C3-Cscycloslkyl sub~ti-tuted by methyl or by chlorine.

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

Group lc: Compounds of formula I in which:

R1 and Rz independently of one another ara hydrogen, chlorins, methyl, methoxy, ethoxy or trifluoromethyl; R3 i9 hydrogen, msthyl, etbyl or trifluoromethyl and R4 i5 cyclopropyl or cyclopropyl sub~titutad by methyl or by chlorine~

Of th~ above-~antioned compou~ds, an ~pscially preferrad group i8 for~ed by tho~ in which R~ ~ Rz ~ hydrogen (~ Group lcc).

Group ld: Compound~ of formula I in which:

Rl is hydrogen; Rz and R3 independantly of one anothar are hydrogen or methyl and R4 i8 cyclopropyl or cyclopropyl substituted by methyl.

1 32q93~

Group 2a: Compounds of formula I in which:

Rl and R2 independently of one another are hydrogen, halogen, Cl-C2alkyl, halomethyl, C1-C~alkoxy or Cl-C2haloalkoxy; R3 is hyclrogen; C1-COalkyl;
C1-C2alkyl substituted by halogen or by hydroxy; cyclopropyl; or cyclo-propyl mono- to trl-substituted by methyl and/or by halogen; and Ro i9 C3-C6cycloalkyl or C3-COcycloalkyl mono- to tri-substituted by methyl and/or by halogen.

Of the above-mentioned compounds, an esp2cially preferred group i9 formed by those in which Rl ~ Rz ~ hydrogen (D Group 2aa).

Group 2b: Compounds o~ formula I in wh1ch:
.

R1 and Rz intependently of one another are hydrogen, fluorlna, chlorine, bromine, methyl, trifluoromethyl, methoxy or difluoromethoxy; R3 is hydrogen; Cl-C~alkyl; C1-C2alkyl substituted by halogen or by hydroxy;
cyclopropyl; or cyclopropyl mono- to tri-substitutad by methyl andlor by hslogen; and R4 i9 C~-CGcycloalkyl or C3-Cocycloalkyl mono- to trl-sub-stituted by methyl and/or by halogen.

Of tha abo~e-mentioned compounds, an especially preferred group i9 formed by thos6 in wbich Rl ~ R2 - hydrogen ~ Group 2bb).

Group 2c: Co~pound~3 of formula I in which:

Rl ant R2 independ~ntly of one anoeher ar0 hydrogon, fluorine, chlorine, methyl, ~rifluoroMethyl, ~ethoxy or difluoro~ethoxy; R3 19 hydrogen;
Cl-C3alkyl; C~-C2alkyl substituted by halogan or by hydroxy; cyclopropyl;
or cyclopropyl mono- to trl-~ubstituted by m~thyl and/or by halogen; and R4 is C3-C6cycloalkyl or C3-Cocycloalkyl mono-to erl-substituted by methyl andlor by halogen.

Of the above-mentioned coMpounds, an especially preferrad group i~ formed by those ln which R1 - R2 ~ hydrag~n (n Group 2cc).

.:

,:

r~ .
- 6 _ 1 3~'~9~

Group 2d: Compounds of formula I in which:

R1 and R2 are hydrogen; R~ i~ C~-C3alkyl; methyl substituted by fluorine, chlorine, bromine or by hydro~y; cyclopropyl; or cyclopropyl substituted by methyl, fluorine, chlorine or by bromine; and R~ i8 C3-C4cycloalkyl or C3-C4cycloalkyl mono- to ~ri-substituted by methyl andtor by fluorina, chlorine or by bromine.

Of the individual substances that are especially preferred there may be ment~oned, for example:
2-phenylamino-4-methyl-6-cyclopropylpyrimidine ~co~p. no. 1.1);
2-phenylamino-4-ethyl-6-cyclopropylpyrimidine ~comp. no. 1.6);
2-phenylamino-4-meehyl-6-(2-methylcyclopropyl~-pyrimiùlne (comp. no. 1.14);
2-phenylamino-4,6-bi 8 ( cyclopropyl)pyrimidine (comp. no. 1.236);
2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimldine (comp. no. 1.48~;
2-phenylamlno-4-fluoromethyl-6-cyclopropylpyrlmidine (comp. no. 1.59);
2-phenylamino-4-hydroxymethyl-6-(2-methylcyclopropyl)-pyrimldine (comp. no. 1.13);
2-phenylamino-4-methyl-6-(2-fluorocyclopropyl~-pyrimidine (comp. no. 1.66~;
2-phenylsmino-4-methyl-6-(2-chlorocyclopropyl)-pyrimidlne ~comp. no. 1.69);
2-phenylsmino-4-mathyl-6-(2-di~luorocyclopropyl)-pyrimidine (comp. no. 1.84);
2-phenylamino-4-fluoromethyl-6-(2-fluorocyclopropyl)-pyrimidine (comp. no. 1.87);
2-phenylamlno-4-fluoromethyl-6-(2-chlorocyclopropyl)-pyrimidine (comp. no. 1.94~;
2-phenylamino-4-fluoromethyl-6-(2-methylcyclopropyl)-pyrimldine (comp. no. 1.108);
2-phenylamino-4-ethyl-6-(2-methylcyclopropyl~-pyrimidine (comp. no. 1.131);
2-(p-fluorophenylamlno) 4-methyl-6 cyclopropylpyrimldine (comp. no. 1.33).

r ~ 32993~

The compounds of formula I are prepared as follows:

1. a phenylguanidine ~3alt of formula IIa ~ NH -cf A (IIa) ~ NH 2 or the free guanidine base of formula IIb ~- - NH - C~ (IIb) ~2 H2 is reacted with a diketone of for~ula III
R3 - 8 - c~2 - 8 - R4 (III~

without solvents or in an aprotic solvent, preferably in a protic so}vent, ~t temperatures of from 60C to 160C, preferably from 60C to llO C; or 2. in a multi-stage proce~s:
2.1 urea of formula IV
~2 (IV) ~ ~2 i~3 reacted with a dik~tons of formula III

R3 ~ - CH2 ~ - R4 (III) in the pr~sencQ of an acld in an inert solvent at temperature~ of from 20C to 140C, preferably from 20C to 40C, and is cyclised to glve a pyrimidins compound of for~ula V

. : ~ : :

- , ; . ,.. ,:: , . , : ::

1 32993~ `

, Na .

snd 2.2 the OH group in the resulting compound of formula V i~ sxchanged for halog0n by further reaction with excess POHal3, in the pre~ance or ~n the absence of a ~olvent, at temperatures of from 50C to llO~C, preferably at the reflux temperature of PO~al3, to yield ,R3 Hal~ (VI) N=- ~

Hal in the above formulae being halogen, especially chlorine or bromine, and 2.3 the resulting compound of formula ~ reacted further wlth an aniline compound of formula VII ~.

Hz~ (VII) dependlng on ~ho reaction conditlons either a) in the pre~ence of 8 proton acceptor, such ac an exces~ of the aniline compound of for~ula VII or an inorganic ba3e, with or without solvents, or b) in the pre3ence of an ac~d in an inert solven~, in each case at temperatures of fro~ 60C to 120C, prefsrably from 80C to 100C; or . ~ - , 1 3~9934 _ 9 _ 3. in a two-stage proces~:
3.1 a guanidine salt of formula VIII

H2N ~ C~ A3 (VIII?

i9 cyclised with a diketone of formula III

R3- 8--CH2- 8 - R4 (III) a) without 301vent9 at temperatures of fro~ 100C to 160C, preferably from 120C to 150C, or b) in an inert solvent at temperature~ of from 30C to 140C, preferably from 60C to 120C, to give a pyrimidine compound of formula IX
,R3 H2N ~ b~ (IX~
~ 4 and 3.2 the rssulting compound of formula IX is reacted with a compound of formula X
~Rl (X~

in the prssence of-a proton acceptor in aprotlc solvents at temperatures of fro~ 30C to 140C, preferably from 60C to 120C, to remova HY, the ~3ubstitu~nts R~ to R4 in for~u}ae II to X being as defined for for~ula I, A being an acid anion snd Y being halogen; or ., ` , .,' '' ' ' . ~ .
: ~ ,, ;. ' ' .

~ 32qq3~

4. ln a mult1-stage process:
4.la~ thiourei of formula XI
~NH2 SsC (XI) ~ Hz is reacted with a diketone of formula III

R3 - ~ - CH2 - ~ - R4 (III~

in the presence of an aoid in an inert solvQnt at temperature~ of from 20C to 140C, preferably from 20C to 60C, and cyclised to give a pyrt~idine compound of formula ~R3 :
HS~ . (XII) ~R4 and the alkali ~etal or slkaline esrth metal 3alt ther00f i8 re3ct0d with a co~pound of formula XIII

ZRs (XIII), whorein Rs i9 C1-COalkyl, or b~nzyl that i9 unsubs~ituted or 3ubstituted by halogen and/or by Cl-C~alkyl and Z is halog~n, ~o give 8 pyrimidine co~pound of formula XIV
: Rl RsS~ (XIV) ~ R4 or b) an isothiuronium ~alt of form~la XV
H2~
H2 ~ A~ ~XV) , . .

19 reacted with 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 i~ likewisa obtained, and 4.2 the resulting compound of formula XIV is oxidisecl with an oxidising agent, for example with a peracid, to give the pyrimidine compound of formula XVI
~R3 s 2 \~ ~ (XVI~
\R4 and 4.3 the resulting compound of formula XVI is reacted with a formylaniline of formula XVII
R1 ._, ~ ~--NHCH0 ~XVII) R2 ~
in an lnert solvent in tha presence of 8 ba~e as proton Rcceptor, st temperatures of from -30C to 120C, to giv~s a compound of formula XVIII

and 4.4 the re~ulting compound of formula XVIII i8 sub~ected to hydrolysis in th~ pre~ence of a ba~e, for example an alkali metal hydroxide, or of an acld, for example 9 hydrohalic acid or ~ulfuric ~cid, in ~ater or aqueous solvant mixtur~, such as aqueous alcohols or dimethylformamide, st te~peratures of from 10C to 110C, preferably from 30C to 60C, the substltuents R1 to ~4 in formulas XI to XVIII being as dsfined for form~la I and A being an acid anion and Y being halogen.

.

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

1 32993~

Compounds of formula I in which R3 is the CH20H group can be prepared by special processes, as follows:

A1.1 the guanidine salt of formula IIa ~D - NH--C ~ A (IIa) .~ ~ H2 ~ -or the gusnidine of formula IIb N~--C ~ (IIb) .~ NH2 i9 r0acted with a ketone of formula XIX

(RGO~2CH_~CH2--l~_R4 (XIX) in which R6 1~ C1-C4alkyl, in a protic solvent or without solventD, at temperatures of from 40C to 160C, preferably from 60C to 110C, to give a pyrimidine compound of formula XX
~CH(OR6~2 NH-- ~ XX) and Al.2 tha re~ulting acetal of formula XX i~ hydrolysed in the presence of an acid, for example a hydrohalic ncld or sulfuric acid, in ~ster or aqùeous ~olvent mixtures, for oxampla ~lth solvents such a~ slcohol~ or dimethylformamide, at temperntures of fro~ 20C to 100C, preferably from 30C to 60C, to give tho pyrimidinealdehyde of formula XXI
R ~CHO
~--NH~ XXI) ~2 ~4 and .

, 1 32qq~

Al.3 the resulting compo~nd of formula XXI i9 hydrogenated with elemental hydrogen using a catslyst or is reduced with a reducing agent, such as sodium borohydride, to give the corresponding alcohol XXII
CH~OH
~ NH~ XXII);

or A~.l the guanidine sale of formula IIa or the guanidine of formula IIb i9 reacted with a d~ketone of formula XXIII

R70CH2~ -CH2-~-R4 (XXIII) in which R7 i9 benzyl that is unsubstituted or substituted by halogen or by Cl-C4alkyl, in a protlc solvent or without solvents, at temperatures of from 40C to 160C, preferably fro~ 60C to 110C, to give a pyrimidine compound of formula XXIV

~ ~--NH~ (XXIV) and in that co~pound A2.2 th~ CN20R7 radicsl-i~ converted into 8 CH20H radlcal by hydroge~a-tion in a solvent, preferably an aprot~c ~olvent, for exa~ple dioxane or tetrahydrofuran, with a catalyst, such aa palladium-on-carbon, preferably Ràney nlck~l, at temperaturas of fro~ 20~C to 90C, preferably fro~
50C to 90~C; or A3.1 the guanidins ~alt of formula IIa or the guanidine of formula IIb i9 reacted wlth a dlk~tone of formula XXV

RôO5H2l~--CH2--C--R4 (XXV~, . ~ . . . . .

. ,' ' ' :-., ,: .: ' : ~ ' ' '' ' 1 32993~

in which R8 is Cl C6alkyl, C3-C~alkenyl or benzyl that i9 un-3ubstituted or subseituted by halogen or by C~-C4alkyl, in a protic solvent or without solvents, at ~emp2ratures of from 40C to 160C, preferably from 60C to 110C, to give a pyrimidine compound XXVI
CHoOR~
NH--~ ~- (XXVI) .~. N=-~
~z R4 and A3.2 with the resulting compound of formula XXVI an ether cleavage i3 carried out with a hydrohalic acid, preferably hydrobromic acid, or a Lewis acid, such as aluminium halide (for example AlCl3) os boron halide ~(Hal)3 (for example BBr3 or BCl3), in aprotic solvents, for example hydrocarbons or halogenated hydrocarbons, at temperatures of from -80C to 30C, preferably from -70C to 20C.

Compounds of formula I in which R3 18 th~ CH2Hal group can be prepared by reacting a compound of formula XXII with phosphorus halide or thionyl halide in the presence of tertiary bases, for e~ample pyridlne or triethylamine, in inert solvents, at temperatures of from O~C to 110C, preferably iro~ 0C to 80C.

Co~pounds of formula I in which R3 i5 the CH2F group can ba prepared by reactin~ a co~pound of formula XXVII
CHzX
NH~ (XXVII) 2 ~1~ .
in whlch X i9 chlosin~ or bromlne, wlth potasaium fluorlde, preferably lyophill ed potasslum fluorid~, in the prasenc~ of ca~alytic amoun~s of ceslum ~luorlde or a Crown ether, for axample 18-Crown-6-ether, in apro-tic 301vents, such as acetonitrile! ~t temperatures of rom 50C to 160C
in a pressure autoclave.

: ~ ' . ~ .

. . , .:

1 32993~

A further process for the preparation of compounds of formula I $n which R3 1~ the CH2~ group consists in fluorinating a compound of ~or~ula XXII
with N,N-diethylaminosulfur trifluoride ~s DAST) in aprotic solvents, such as dichloromethane, chloroform, tetrahydrofuran or dioYane, at temperatures of from 0C to 100C, preferably from 10C to 50C.

In the above for~ulae XVIII to XXVII too, Rl, R2 and R4 are as defined for formula I.

In the described proces3e~, in compounds of formulae IIa and VIII the following salt radicals, for example, are suitsble for the acid anion A :
carbonate, hydrogen carbonate, nltrate, halide, sulfate and hydrogen ~ulfate.

In the processe~ described above, in the compound of formula XV the following salts, for example, are suitable for the acid anion A~: halide, 3ulfate and hydrogen sulfate.

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

The acids u~ed are especially inorganic acids, such as, for example, hydrohalic acid~, for zxample hydrofluoric acid, hydrochloric acid or hydrobromlc acid, and ~l~o sulfuric acid, pho-phoric scid or nitIic acid;
however, s~ltable organic acids may also be u~ed, such as, inter alia, acetlc acid and tolueneYulfonic acid.

As proton acceptors there are used, for exa~ple, inorganic or organic base~, ~uch as, for example, alkali m2tal or alkaline earth metal compounds, for exa~plo the hydroxides, oxides or carbonate~ of lithium, sodium, potassium, magne~ium, cslcium~ strontium and barium, or also hydride~, such as, for example, sodium hydride. A~ organic baseY there may be mentioned, for example, tertiary smines, such as triethylamine, triethylenediamlne, pyrldine.

In the proce~ses described above, for example, the follo~ing solvents may be used, dependent on the particular reactiQn condltlon3, in addition to those already mentioned:

: ~, ' .

f ' 1 3 2 9 9 3 4 Halogenated hydrocarbons, especially chlorinated hydrocarbons, s~ch as tetrachloroethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, chloronaphthalens, carbon tetra-chlaride, trlchloroethane, trichloroethylene, pentachloroethane, dl-fluorobenzene, 1,2-dichloroethana, l,l-dichloroethane, 1,2-cis-dichloro-ethylene, chlorobenzene, fluoroben2ene7 bromobenzene, dichlorobenzene, dibromobenzene, chlorotoluene, trichlorotoluene; ethers, such as ethyl propyl ether, methyl tert.-butyl ether, n-butyl ethyl ether, di-n-butyl ethar, diisobutyl ether, diisoamyl ether, diisopropyl ether, anisole, cyclohe~yl methyl ether, diethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, thioanisole, dichlorodiethyl ether; nitrohydro-carbons, such as nitromethane, nitroethane, nitrobenzene, chloronitro-benzene, o-nitrotoluens9 nitriles, such as acetonitrile, butyronitri}e, isobutyronitrile, benzonitrile, m-chlorobenzonitrile; aliphatic or cyclo-aliphatic hydrocarbons, such as heptane, hexane, octane, nonane, cymol, petroleum fractions withln a bolllng point range of from 70C to 190C, cyclohexane, msthylcyclohexane, decalin, petroleum ether, ligroin, tri-methylpentsne, such as 2,3,3-trimethylpentanei esters, such as ethyl acetate, ethyl acetoacetate, isobutyl acetate; amides, for example formamide, methylformamide, dlmethylformamide; ~etones, such as scetone, methyl ethyl ketone; slcohols, especially lower aliphatic alrohol~, such as, for example, ~ethanol, ethsnol, n-propanol, isopropanol and the butanol isomer~; and, where approprlate, a}so water. A1BO ~uitable are mixture~ of the ~entioned solv0nts and dlluents.

Methods of synthssis that are analogous to tha above-described prepara-tlon processes ha~e been published ln the literature.

As references there may be mentioned:

Process 1: A. Kreutzberger and J. Gillessen, J. Heterocycllc Chem. 22, 101 (1985). -Process 2:, Stage 2.1: O. Stark, Ber. Dt~ch. Cham. Ges. 42, 699 (1909?;
J. Hale, J. Am. Chem. Soc. 36, 104 (1914); G.M. Kosolapoff, J. Org.
Chsm. 26, 1895 (1961~. Staga 2.2: St. Angerstsin, Ber. Dtsch. Chem, Ges. 34, 3956 (1901); G.~. Ko~olapoff, J. Org. Chem. 26, 1895 (1961~.

.' ,. ..

~, i, ~ .

~ - 17 ~ 1 32q9 34 Stage 2.3: M. P. V. Boarland and J. F. W. McOmie, J. Chem. Soc.
1951, 1218; T. Matsukawa 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 intexmediates in the preparation of the compounds of formula I, are novel.
Compounds of formula XXX form the subject of the first divisional application. Compounds of formula XXI are the subject of this second divisional application.
1) Compounds of formula XXX

R

o~~ (XXX) ~N 5~\

., in which: Ro is halogen or R5SO2; R3 is hydrogen; Cl-C~alkyl; or Cl-C4alkyl substi~uted 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-C8alkyl or benzyl that is unsubstituted or substituted by halogen and/or .

.
- -.

1 3~ 9 ~ :~ 4 21489-7555E
,:
by Cl-C4alkyl. Chlorine and bromine are preferred as halogen substituent Ro.
2~ Compounds of formula XXI

CHO
Rl N - ~/

\ ~ NH .~ ~, (XXI) , ~ . N~=~\

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 adv~ntageous biocidal spectrum against insects and phytopatho-genic 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 ln 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, .

1 3 2 9 q 3 ~ 21489-7555E

against the phytopathogenic fungi belonging to the following classes: Fungi imper~ecti tespecially 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 oE 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 additionl compounds of formula I are effective against insect pestsl 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 relates to a method of treating plants, which comprises applying thereto the novel compounds of formula I
or the novel compositions.

, .

~ !

~ 1 32993~

Target crops to be protected within ehe scope of the present invention comprise 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, strawberries, raspberries and blsckberries), leguminous plants (beans, lentils, peas, soybeans), oil plants (rape, mustard~ poppy, olives, sunflowers, coconut, castor oil plants, cocoa bean3, groundnuts), cucumbex plants (cucumber, marrows, melons~, fibre plants (cotton, fl8x, hemp, Jute), citru3 fruit (orange3, lemons, grapefruit, mandarins~, vegetables ~spinach, lettuce, ssparagus, cabbages, carrots, onions, tomatoe~, potatoes, paprika), lauraceae (avocados7 cinnamon, camphor), or plants such as tobacco, nuts, coffee, sugar cane, tea, pepper, vine~, hops, bananas and natural rubber plants, as well as ornamentals.

The compound3 of formula I are normally applled ln the form of composi-tlon~ and can be spplied to the crop srea or plant to be treated, simul-t&neously or in succession, with further actlve substances. These sctive 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 mixture~ of several of these preparations, if deaired together with further carriers, surfactants or application-promoting ad~uvant3 customarily employed in the art of formulation.
... .
Suitable carriars and ad~uvants cAn be solid or liquid and corre~pond to the substances ordinarily employed in formulation techn~logy, e.g.
natural or regenersted ~ineral substances, solvents, disp0r3ants, wetting agents, tackifiers, ehickeners, binders or fertilisers.

A pre~erred method of applying a compound of for~ula I, or an agro-chemical composition which contains at least one of said compounds, i9 foliar application. The number of applications snd the rate of applica-tion depend on the risk of infestation by the corresponding psthogen.
However, the compound3 of for~ula 1 can also penetrate the plant through the roots via the soil (systemic action) if th~ locus of the plant is impregnsted wlth a liquid formulation, or if the compound~ ~re applied in . .
,: ~ ' ' 1 32~q34 solid form to the ~oil, e.g. in granular form (ssil application~. In paddy rice crops, such granulates may be applied in metered amounts to the flooded rice field. The compound3 of formula I may, however, also be applied to seeds (coating) either by impregnating the seeds with a liquid formulation containing a ~ompound 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 adjuvant3 conventionally employed in the art of formulation, and are for this purpose advantageously formulated in known ~anner e.g. into emulsifiable concentrates, coatable pastes, directly sprayable or dilutable ~olutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulatioDs in e.g.
polymer substances. As with the nature of the compo~itions, the metbods of application, such as spraying, atomising, dusting, scsttering, coating or pouring, are chosen in accortance with the intended objectives and the prevalling clrcumstances. Advant~geous rete0 of appllcation are normally from 50 g to 5 kg of active ingredent ~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.

Ths formulations, i.e. the co~positions, preparations or mixture~
containing the compound (active ingredient) of for~ula I and, where appropriate, ~ ~olid or liquid ad~uvant, are prepsret in known manner, e.g. by homogeneously mixing and/or grinding the active ingr2dients with extender3, o.gO solvent~, ~olid carrier~i and, wher~ appropriate, surface-activ~ compounds (surfactants).

Suitable solvent3 are: aromatic hydrocarbons, prefersbly the fractions containing 8 to 12 csrbon atoms, e.g. xylene mixtures or substituted naphthalenes, phthalatea ~uch as dibutyl phthalate or dioctyl phthalate, aliphatic hydrocarbons such a3 cyclohexan0 or paraffins, alcohols and glycol3 and their ~thers and es~er~, ~uch a~ sthanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones such as cyclohexanone, strongly polar ~olvents, such a0 N-~ethyl-2-pyrrolidone, di~ethyl sulfoxid~ or dimethylformamide, as w011 as vegetable 0119 or epoxidised vegetable oils, such a~ epoxidised coconut oll or ~oybean oil;
or water.

: .
' 1 32q~34 The solid carriers used e.g. for dusts and dispersible powders are normally natural mineral fillers, such as calcite, talcum, kaolin, montmorillonite or aetapulgite. In order to improve the physical properties it i9 also possible to add highly dispersed silicic acid or highly dispersed absorbent polymers. Suitable granulated adsorptive csrriers are porou3 types, for example pumice, broken brick, sepiolite or bentonite; and suitable nonsorbent carriers are, for example, calcite or sand. In addition, a great number of pregranulated materials of inorganic nature can be used, e.g. especially dolomite or pulverised plant re3idue~.

Particularly advantageous application-promoting adjuvants which are able to reducs substantially the rate of application sre al90 natural (animal or vegetable) or synthetic phosphollplds of the series of the caphalins and lecithins, which can be obtained 0.g. from soybean~.

Depending on the nature of the compound of formula I to be formul~ted, suitable surface-active compounds are non-ionic, cationic andtor anionic surfactants having good emulsifying, dispersing and wetting properties.
The term "surfactants" will also be understood ag comprising mixtures of surfactants.

Both 80 call0d water-soluble soaps and also water-301uble synthetic surface-active compounds are suitable anionic surfactants.

Suitable sosps are the alkali metsl salts, alkaline earth metal ~alts or unsubstituted or subst1tuted ~m~onium salts of hlgher fatty acid~
(C1o-C22), e.~. the sodium or pota~sium salts of oleic or stearic acid or of natural fatty acid ~lxtures which can be obtained e.g. fro~ coconut oil or tallo~ oil. Mention may also be made of fatty acid ~ethyllaurin salts.

More frequently, however, so-called synthetic surfactants are used, especislly alkanesulfonates, Xatty alcohol sulfates, sulonated benzimidazole deriYatives or slkylsulfonate3.

: .

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1 32q934 The fatty alcohol sulfonates or sulfates are usually in the form of alkali metal 3alts~ alkaline earth metal ~alts or unsubstituted or sub-stituted ammonium salt3 and contain a Cg-Cz2alkyl radical which 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 obtained from natural fatty acids. These compounds also comprise the salts of sulfated and sulfonated fatty alcohol/ethylene oxide adducts. The sulfonated benzi~idszole terivatives preferably con-tain 2 sulfonic acid groups and one fatty acid radical containing 8 to 22 carbon atoms. Exa~pleg o~ alkylsrylsulfonates are the sodiu~, calcium or triethanola~ine salts of dodecylbenzenesulfonic scid, dibutylnaphtha-lenesulfonic acid, or of a condensate of naphthalenesulfonic acid and formaldehyde.

Also suitable are corresponting phosphstes, e.g. salts of the phosphoric acid ester of an adduct of p-nonylphenol wlth 4 to 14 moles of ethylena oxide.

Non-ionic surfartsnts are preferably polyglycol ether derivative3 of allphatic or cycloaliphatlc alcohols, or ~aturatod or unsaturated fatty acidg and slkylphenols, said derivAtives containing 3 to 30 glycol ether group~ and 8 to 20 carbon stoms ln the (aliphatic) hydrocarbon moiety and 6 to 18 carbon atoms in the slkyl moiety of the alkylphenols.

Furthar suitsble non-ionic surfactants are the water-soluble adducts ofpolyethylene oxida with polypropylene glycol, ethylenedia~inopolypropy-len~ glycol and ~lkylpolypropylQne glycol coneaining 1 to 10 carbon atoms in the alkyl chain, which adducts contain 20 to 250 othylene glycol ether groups and 10 to 100 propylene glycol ether groups. TheYe compound3 usually contain 1 to 5 sthylene glycol units per propylene glycol unit.

Representative exa~ples of non-ionic surfactants are nonylphenolpoly-ethoxy~thanols, castor oil polyglycol etherY, polypropylenelpolyethylene oxide adduct~, tributylphenoxypolyethylsn~ethanol, polyethylene glycol and octylphenoxypolyethoxyethanol.

Patty acid esterR of polyoxyethylene 30rbitan, e.g. polyoxyethylenQ
sorbitan trioleate, ars also suitable non-~onic Yurfactantg.

' :

- 23 - 1 329 9 3 ~

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 ethyl-sulfates, 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 %, 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: Preparation of 2-phenylamino-4-methyl-6-cyclo-propylp~rimidine .

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10 g (51 mmol) of phenylguanidine hydrogen carbonate and 9.7 g ~77 mmol) of l-cyclopropyl-1,3-butanedione are heated at 110C for 6 hours with stirrin~, the evolution of carbon dioxide which occurs subsiding as the reaction progres~es. After the dark browl~ emulslon has been cooled to room temperature, 50 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 solvent i9 evaporated. The dark brown oil which remains (3 13.1 g) is purified by column chromatography over silica gel ~diethyl ether/toluene: 5/3). After the eluant mixture has been 2vsporated off, the brown oil i9 made to crystallise and recrystalllsed from diethyl sther/petrolaum ether at 30-50C. Light-brown crystals are obtained.
Melt~ng point: 67-69C; yield: 8.55 g (38 m~ol) (~ 74.5 % of the theoretical yield).

E~ample 1.2: Preparation of ~-anilino-4-formyldiethyl-acetal~6-cyclo-propyl~yrimidine ~CH~OC2Hs ) z NH~
.=. N=-. _ .

11.7 g (59.2 mmol) of phenylguanidine hydrogen carbonate and 13.3 g (62.2 ~mol~ of 1-cyclopropyl-3-formyldlethylacetal-1,3-propanedlone in 40 ml of ethanol are heated under reflux for 5 hours with stlrring, the evolution of carbon dioxide subsiding as the reactlon progresses. After the dark brown emulsion has been cooled to room temperature, 80 ml of dlethyl ether are added and the mixture i9 wa~hed twice with 30 ml of water ssch time, dried over sodium sulfate and filtered, and the solvent i9 evaporated. The dar~ brown oll which remsin~ (17 g) is puri~led by column chromatography over sillca gel (toluenetethyl acetate: 512). After the eluant ~i~ture has been evaporated off, a reddlsh brown oll re~ains which has a refractlve index nDS: 1.5815. Yield: 15 g (48 mmol; 81.1 %
of the theoretlcal yield).

, ` 1 32993~

E~ample 1.3: Prepar~tion of 2-anilino-4-formyl-6-cyclo-propylpyrimidine ~CEIO
NH-- ~ ~- (Comp. no. 2.1) .=. =.
I~

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 hour~ with vigorous stirring and, after the addition of 2 g (19.6 mmol) of concentratecl hydrochloric acid, stirring is continuet for a further 24 hour~ at that temperature. After the beige-coloured suspension has been cooled to room temperatural 50 ml of ethyL acetate sre added thereto and the mixture i5 rendered neutral with 7 ml of 30 % sodium hydroxide solution. The ethyl acetate solution i8 then separated off, dried over sodium ~ulfate and filtered, and the solvent i9 evaporated. For purification, the brownish solld i9 re-crystallised from 20 ml of isopropanol in the presence of active carbon.
The ysllowish crystal3 melt at 112-114C. Yield: 7.9 g (33 mmol; 84 % of the theoretical yleld).
~ample 1.4: Pre~aration of 2-anilino-4-hydroxymethyl-6-cyclopr pyrimldine ~CHzOH
NH~ (Comp. no. 1.4 !' -a~ 2.3 g (60 mmol) of aodium borohydride sra sdded in portions at room temperaturo, within a period of 15 minutes, with stirring, to 14.1 g (59 mmol? of 2-aoillno-4-formyl-6-cyclopropylpy~imidina in 350 ml of ab301ute methsnol, whereupon the reaction mixture warm3 up to 28C with evolution of hydrogen. After 4 hour3 the mixture i~ acidified by the dropwise addi-tion of 10 ml of concentrated hydrochloric acid, 120 ml of 10 % qodiu~
hydrogen carbonate solutio~ are added dropwise, and the mixture is then diluted with 250 ml of w~ter. The resulting precipitate is filtered off, dried, largely dissolved in 600 ml of diethyl ether at elevated tempera-ture, treated with ective carbon nd filtered. The clear filtrate i3 .
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1 3299~4 - ~6 -concentrated until it becomes turbid and i9 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 % o~ the theoretical yield~.

b) 5.9 g (23 mmol) of 2-anilino-4-methoxymethyl-6-cyclopropylpyrimidine, prepared from phenylguanidine and 1-cyclopropyl-4-methoxy-1,3-butane-dione, are dissolved in 200 ml of dichloromethane and the solution i~ ~ -cooled to -68C. 6.8 g ( 27 mmol? of boron tribromide are ~lowly added dropwi3e to the salmon-coloured solution within a period of half an hour, with vigorous stirring, and the cooling bath ~ 9 then removed and stirring is continued for a further 2 hours at room temperature. After the ~ddi-tion of 150 g of ice-water, the precipitated cruds produot i9 filtered off and recry~talli3ed from methanol using active carbon. The light-yellow crystals melt at 124-126C. Yield: 4.7 g ~19.5 mmol; 84.7 % of tha theoretical yield).
xample 1.5: Preparatlon of 2-phenylamino-4-bromomethyl-6-cyclopropyl-pyrimidine ~CH2Br ~ NH~ - (Comp. no. 1.4) 15.6 g ~75 m~ol) of thionyl bromide in 50 ml of diethyl ether ara added ~-dropwiso ~ithln 8 poriod of half an hour, with stirring, to 12 g (50 mmol) of 2-phonylaMino-4-hydroxymethyl-6-cyclopropylpyrimidine ant 0.4 g ~50 ~ol) of pyridine in 350 ml of diethyl ether. A~ter stlrring for 2 hours at room temperature, a further 0.4 g (50 mmol) of pyridine aro added and the mixture i9 hested unde~ reflux for 5 hour~. After cool-ing to room temper&ture, 200 ml of wster are added and the p~ i9 adjusted to 7 by the drop~ise addition o~ 140 ml of saturated ~odtum hydrogen carbonate solution. The diethyl ether phsse i~ separated off and then washed twice with 100 ml of water each time, dried over aodium ~ulfate and filtered, and the solvent is evaporQted. The brown oil which remains is purified by column chromatography over silica gel (toluene/chloroform/di0thyl ethertpetroleum ether (b.p. SQ-70C~:

: ' , ' ~ ' ;,: ,-~ 1 32q934 51311/1). After the eluant mixture has been evaporat0d off, the yellow oil is diluted with diethyl ether/petroleum ether (b.p. 50-70C~ 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?.
xample 1.6: Preparation of 2-phenylamino-4-fluoromethyl-6-~yclopropyl-pyrimidine ~CH2F
~ ~--N~ - (Comp. no. 1.59 ~- N=.

a) 3.9 g (12.8 ~mol) of 2-phenylamino-4-bromomethyl-6-cyclopropylpyrimi-dine, 1.5 g (26 mmol) of ~pray-dried potas3ium fluoride and 0.3 g (1.13 mmol~ of 18-Crown-6-ether are hested under reflux for 40 hours :Ln S0 ml of acetonitrile. A further 0.75 g (13 mmol) of potassium fluoride i~ then addad and the mixture i~ heated for 22 hours. To complete the reaction, a furthar 0.75 g (13 mmol) of spray-dried potAssium fluoride and 0.1 g (0.38 m~ol) of 18-Crown-6-ether ar0 addod and the mixture is heated under reflux for a frther 24 hQurs. After the suspension has besn cooled to room temperature, 150 ml of diethyl ether Are added and the mixture is wa~hed three tim0~ with 20 ml of water each time, drled over sodium sulfato and filtered, and the solvent is svaporated. Tha brown oil which remains iG purifiad by column chromatography over ~ilica gel (toluenelchloroform/diethyl 0thertpetroleum ether (b.p. 50-70C):
513/1/1). A~ter th~ ~luant mixture h~s been evaporat~d off, the yellow oil i8 diluted with 10 ml of petroleum ether (b.p. 50-70C~ and cry3tallised at reduced temporature. The yellow crystals melt at 48-52C;
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 arc slowly added dropwise w~thin a period of ona hour, with stirring, to a suspension of 9.1 g (37.8 mmol) of 2-phenylamino-4-hydroxymethyl-6-cyclopropyIpyrimidine in 80 ml of dichloromethane. After tha addition of 50 ml of ice-water, 50 ml o~ 10 ~ aqueous 30dium hydrogen carbonate solution are atded dropwise. Whan tha evolution of carbon dioxide has ceased, the orgsnic phase is ~eparated off and the aqueous , ~ : . . ~, ~, . .

1 329~4 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 i9 diluted with 20 ml of petroleum ether (b.p. 50-70C) and crystallised at reduced temperature. The yellowish crystals malt at 50-52C. Yield: 4.9 g (20.1 mmol; 53 % of the theoretical yield).

Exam~_e 1.7: Preparation of 2-hydroxy-4-methyl-6-cyclo-propylpyrimidine ~CN~
HO~

!

15 ml of concentrated hydrochloric aaid are ndded at room temperature to 6 g (lOQ mmol~ of urea and 12.6 g (100 mmol) of 1-cyclopropyl-1,3-butane-dione in 35 ml of ethanol. After the mlxture has stood for 10 days at room temperatura, it i9 concentrated in 8 rotary evaporstor ~t a bath temperature not exceeding 45~C. The res~due i8 dissolved in 20 ml of ethanol, th~ hydrochlorida of the r~action product pracipitatin~ after a short tima. 20 ml of diethyl ether are added with stirring, and ths precipitsted white crystals are filt~red off, washad w~th an ethanol/di0thyl ether mixture and dried. Concentration of tha filtrate and recrystRlli~stion from an ethanol/diethyl ether mixture: lt2 yield a further quantity of hydrochlorlde. The whlta cry~tals melt > 230C.
Yiald: hydrochloride 12.6 g (67.5 mmol; 67.5 % of the theoretical yield~.

Example 1.~: Preparation of 2-chloro-4-methyl-6-cyclo-propylpyrimidine ~C113 Cl~ Comp. no. 3.1) _. :

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- 29 _ 1 32993~
52.8 g (0.24 mol) of 2-hydroxy-4-methyl-6-cyclopropylpyrimidine 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 hour3 ~t 110~, it i9 coo~ed to room temperature and transferred onto an ice-waterlmethylene chloride mixture, with stirring.
The organic phase is separated off and washed with saturated aqueous sodium hydrogen carbonate solution until ne~tral. Removal of the sol~ent by ~vaporation yields 116.4 g of oil, which is composed of the reaction product and diethylaniline. Separation of the diethylaniline and purifi-cation of the crude reaction product are Qffectad by column chromato-graphy over silica gel (hexaneldiethyl acetate: 311~. The colourles~ oil which crystallises after Qeveral dsys has a refractive index nD5:
1.5419; yield: 35.7 g (0.21 mol: 87.5 % of the theoretical yield~;
melting polnt: 33-34C.

Example l.9: Preparatlon of 2-(m-fluorophenylsmino)-4-methyl-6-cyclo-propylpyrimidlne ~CH3 -NH-- ~ ~- (Comp. no. 1.63) ._. :

A solution of 5.5 g (50~mmol) of 3-fluoroaniline snd 9.3 g (55 ~mol) of 2-chloro-4~methyl-6-cyclopropylpyrimidine in 100 ml of ethanol is ad~ust0d to p~ 1 with 5 ml o~ concentrated hydrochloric acid, with stirr-ing, and is then he2ted under reflux for 18 hours. After the bro~n smul-~ion has been cooled to room temperature, lt i9 rendered alkali~e with 10 ml of 30 % ammonia, poured onto 100 ml of ice-w~t~r and extracted twice with lS0 ml of diethyl ether each time. Ths combined extract~ ar~
washed with 50 ml of water, dried over sodium sul~ate and fllter0d, and ths solvent i~ evaporated. The yellowi~h crystal~ which remain are puri-fisd by recrystallisation from diisopropyl ether/petrol~um ether (b.p. 5Q-70C). The whita crystals melt at 87-89C; yield: 8.3 g (34 mmol; 68 æ of the theoretical yield).

, - 30 ~.
The following compounds of formula I can be prepared ln 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 th~ formuls Rl ~ ~CNO

_ _ R~ R~ Phy lc 1 .

2.1 H H ~ ,cl m.p. 112-114UC

2.2 H H ~CH~ m.p. 123-127C .

2.3 H H ! m.p. 87-90C

2.4 4-Cl H ~F

2.5 ~ H --~! m.p. 128-132C

2.6 3-F H

2.74-7 ~ _,/' _ .: . ',~

' ' ' ` ~ 3299~

Tablc 3: ,R3 Hal~
~R4 . _ _ . ,, .... _.
Comp . Hal R3 R4 Physical no. ~ _ cons ant 3.1 Cl -CH3 ~CH3 P 33 34C

3. 2 Cl -CH3 _. i nDS: 1 . 5432 3.3 Cl -CH3 _,~ ~.

3. 4 Cl -CH3 _~ . ;

3.5 Cl -CH3 ~'\ ~I

~ (J_~ ~

. .

~^
1 329~34 Table 3: Continuation _ .
Comp. Hal R3 R4 Physical no. constant __ .. _ _ 3.11 Cl H ~ . ~

3.12 Cl -C4Hg-n ~ . ..

3.13 Cl -CHClz C~- .

3.14 Cl -CH3 --`!~ r ~ -3.15 Cl -CH3 ~Cl :

3.16 Cl -CH3 ~ cCl3 3.17 Cl -CzHs _.~;m.p. 32-35C :

. 3.18 C1 -CFzCF3 _.~;

3.19 Cl -C~3 -.~I~C1 . -3 20 Br -CH3 ~ ~! ~~~ - ~

!

~ 329`93~

Tablc 3: Continuation . . . .
Comp. Hal R3 R4 Physical no. constant _ - . . __ ..
3.21 Cl -c2Hs fH~ ~.p. 28-31C

3.22 Cl -CH3 --~! -3.23 Cl -C4Hg-sek. ~F

3.24 Cl -CH3 --~! m.p. 42-45C

3-25 ¦ Cl ~ l~Cl 3.26 Cl -CHJ fN!~

3.27 Cl -CH3 ~-~!\Cl ~CH3 ~CH3 3.28 Cl ~-~1 --~

3.29 ~ 3r ¦ -~N~

3 30 Br -CH3 ~I _ .

1 32q~3~

Table 3: Continuation Comp. Hal ~ -- R4 Phy~3ical no. constant _ . ._ _ . .--- - .. _ 3.31 Cl -C3H7-n -.~j 3.32 Cl -CH3 ~C3;

3.33 Br -CZHs ~!

3.34 Cl -CF3 ~

3.35 Br -C2Hs _.~j .
~Cl I.36 Cl -CH3 ~F

3.37 Cl -CH3 - ~!~F : ~ 1 ~CH3 3.38 Cl -CH3 _.~¦~CH3 : ~.

3.39 Cl ~CClF2 --~!

3 40 Cl - ~! -.~1 ` :`

3.41 Cl -CH2Cl -.~¦

3.42 Cl -CH2F --~¦

: 3.43 Br ~ ~'~;

3.44 Br -CH~F -.~¦

3 4S C 1 - CHzOH -.~¦ ~.

- 66 - 1 32~934 Co~p . Hal ~3 R4 Physical .,.
no. _ constant 3. 46 ~r --CH2OH ~ _ _ 1 32~93~
- 67 - :

Tabl~ 4: ~R3 N-~
RsS02~~
N---Comp. Rs ~ R3 R4 Physical no. . constant _ .~
4.1 CH3 -CH3 _-~; . .

4.2 CH3 -CH 3 _.

4.3 C4H9-n -CH3 _ ~¦

4.4 CH3 -CH3 _. ¦

4.5 CH2--~ ~. -CH3 --'! ~ r 4.6 CH3 -CH3 ~j 4.7 -CH~ -CH3 -CN3 ~j 4.8 CzH5 -CH3 ~ cl 4~9 I C~ -C~ r 4 10 CH~ _. I _. I ~.p. 84-a90c .

' ' " '''` ' ~

1 32qq3~
- 6~ - :

Table 4: Continuation ~ . . _ .
Co p. Rs R~ R4 Phy~ical . constant ,__ ___ - __ 4.11 CH2~ - ff l -CH~ ~CH3 4.12 CR~ -CH~ _.~j 4.13 CH3 ff HJ ~F

4,14 CHJ -CH~ ~-~1 C

4.15 C2Hs -CH3 --~!

4.16 CH3 ff 2Hs ~¦ m.p. 64-68C

4.17 C2Hs ff H3 -.~¦

4.18 CJH7-n -CH3 CN~

4.19 CH3 -CH3 --~!~CH3 4.20 C~N~-n -CH3 ~I ~ _ ~. ~

. .
' ~ ~ ' ' ;, - ' 1 ~29934 Table 4: Continuation _ .
Comp. Rs R3 R4 Physical no. constant _ . ~F :

4.21 CH3 -CH3 ~F

4.22 C~H7-n -CH3 ~F

4.23 CH3 -CH3 ~CHJ

4.24 CHJ ~CzHs ~Cl 4.2 5 CHJ - CHJ ~CH3.

4.26 CzHs -CHJ ~Cl 4.27 CHJ ~CH3 ~CH3 4.28 C~3 -CH3 --~!~CH3 4.29 CH3 -.~¦ ~Cl m.p. 54-58C .

4.30 C~H7-n -CH3 \i .

: ,~

. ~;
' ~
. .

1 32q934 2. Formulation Examples for liquid actlve ingredients of formula I
(throughout, percentage~ are by weight?

2.1. Emul~ifiable concentrate~ a) b~ c~
_ a compound of Table 1 25 %40 % 50 %
calcium dodecylbenzenesulfonate 5 %8 % 6 %
castor oil polyethylene glycol ether t36 moles of ethylene o~ide~ 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 concentratas by dilution with water.

2.2. Solutions a) b) c) d) a compound of Tsble 1 80 %10 % S % gS %
ethylene glycol mQnomethyl ether 20 % - - -polyethylene glycol (mol. wt. 400) - 70 % - -~-methyl-2-pyrrolidone - 20 % - -epoxidised coconut oil - - 1 % 5 %
petroleum fraction (boiling range 160-190C) - - 94 %

These solutions are suitable for application in the form of micro-drops.

2.3. Grsnulate~ a) b) a compound of Table 1 5 %10 %
kaolin 94 %
highly dispersed silicic acid 1 %
attapulgite - 90 %

' ~1, . ' ' ' ~' , ' ';

1 32~934 The active ingredient i9 dissolved in methylene chloride, the solution i9 sprayed oneo the carrier, and the solvent is subsequently evaporated off in vacuo.

2.4. Dusts a) b) a compound of Table 1 2 % 5 %
highly dispersed ~iliclc scid 1 % 5 %
talcum 97 %
kaolin ~ 90 %

Ready-for-use dust~ are obtained by intlmately mixing the carriers withthe active ingredient.

Formulation Example3 for solid active ingredient~ of formula I (through-out, percentages are by weight~

2.5 Wettable powders a) b) c) a compound of Table 1 25 % 50 %75 %
sodium lignosùlfonate 5 % 5 %
sodium laurylsulfate 3 % - 5 %
sodium diisobutylnaphthalene-sulfonate - 6 %lO 70 octylphenol polyethylene glycol ether (7-8 moles of athylena oxide) - ~ %
highly dispersed 9ilicic acid 5 % 10 % 10 %
kaolin 62 % 27 %

The active ingradient i9 thoroughly mixed wlth the adiuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspen3ions of the de~ired concentration.

2.6. Emulsifiable concentrate a co~pound of Tabla l lO %
octylphenol polyethylene glycol ether (4-5 moles of ethylene oxide) 3 %

' .:. . , .:

/ -1 32993~

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 dllution with water.

2.7. Du3ts a~ b) a compound of Table 1 S % 8 %
talcum 95 %
kaolin - 92 %

Ready-for-use dusts are obtained by mlxing the active ingredient with the carrier and grinding the mixture in a suitabl~ mlll.

2.3. Extruder granulate a compound of Table 1 10 %
sodium lignosulfonate ~ %
carboxymethylcellulose 1 %
kaolin 87 %

The ac~ive ingredient i9 mixed and ground ~ith the ad~uvants, and the mixture 19 subsequently moistened with water. The mixture i9 extruded and then dried in a strea~ of air.

2.9. Coa~ed granulate a compound of Table 1 3 %
polyethylene glycol (mol. wt. 200) 3 %
kaolin 94 %

The flnely ground active ingredient i9 uniformly applied, in a mi~er, to the kaolin moi~tened with polyethylene glycol. Non-dusty coated granu-lates are obtained in this manner.

1 3 2 9 q 3 ~r 2.10. Suspension concentrate a compound of Table 1 40 %
ethylene glycol 10 %
nonylphenol polyethylene glycol ether (15 moles of ethylene oxide~ 6 ~0 sodium ligno~ulfonate 10 %
csrboxymethylcellulose 1 %
37 % aqueous formaldehyde solution 0.2 %
~ilicone oil in the form of a 75 %
aqueous emulsion 0.8 %
water 32 %

The finely ground activQ ingretient i9 intimat01y mixed with the adju-vants, giving a suspension concentrate from whlch su3pensions of sny desired concentration can be obtained by dilution with water.

3. Biological Example~

Example 3.1: Action a~ain~t Venturia inaequalis on apple shoot~
Residual protective action Apple cuttings with 10-20 cm long fresh shoots are sprayed with a spray mixture (00006 % active ingredient) prepared from 8 wettable powder for-mulation of the test compound. The treated plants are infected 24 hours later with i conitia suspenslon of the fuDgu~. The plant3 are then incu-bated for 5 days at 90-100 % relative hu~idity and stood in a greenhouse for a further 10 days at 20-24C. Scab lnfestation is evaluated 15 tays sfter infection.

Compounds of Table 1 exhibit good activity against Venturia (le~s 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 O to 10 %. On the other hand, Vsnturia attack is 100 % in untreated snd infected control plsnts.

:~

1 329q~

Example 3.2: Action against ~otrytis cinerea on apples Residual protectlve action Artificially damaged apples ara treated by the dropwise appllcation to the damaged sites of a spray mi~ture (0.002 % active ingredient) prepared from a wettable powder formulation of the test compound. The treated fruits are then inoculated with a spore 3uspension of the fungus and incubated for one week at high humidity and about 20C. Evaluatlon i8 made by counting the rotted damaged sites and deriving the fungicidal activity of the test compound therefrom.

Compounds of Table 1 e~hibit good activity again~t Botrytis (less than 20 % attack). Thu~ 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, 1.1581 }.180 and 1.236 reduce Botrytis attsck to 0 to 10 %. On the other hand, Botrytis attack i9 100 % on untreated and infected control plant3.

Example 3.3: Action agalnst Ery~iphe graminis on barley Residusl protective actlo~
Barley plants about 8 cm in height are sprayed with a spray mixture (0.006 % active ingrediant) prep~red from a wettable powder formulatiGn of the test compound. The treated plants are dusted with con~dla of the fungus after 3 to 4 hours. The lnfected barley plants are stood in a greenhouse at about 22C. The fungus attack i8 evaluated after 10 days.

Co~pound3 of Table 1 exhibit good activity against Erysiphe (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.ô4, 1.87, 1094, 1.108, 1.131, 1.158 and 1.236 reduce Erysiphe attack to 0 to 10 ~Oo On the other hand, Ery~iphe attack ls 100 %
on untreated and lnfected control plants.

Example_3.4- Action a~nst Helmlnthosporium gramineum ~heat grains are contaminated wlth a spore susponsion of the fungus and dried. The contamlnatad grains are dressed wlth a suspenRion of the test compound prepared from a wettable powder (600 ppm of active ingredient, based on the welght of the seeds). Two days laeer the grains are placed 1 32~934 in suitable sgar dishes and the development of fungus colonies around the grains ls assessed after snother 4 days. The effectiveness of ths test compounds i9 evaluated on the ba3is of the number and size of the colonies. The compounds of the Table sub3tantlally prevent fungus attack (0 to lO %).

Example 3.5- Action against Colletotrichum lagenarium on cucu~bers After a cultivation period of two weaks, cuçumber plants are sprayed with a 3pray ~ixture (concentration 0.002 %~ prepared from a wettable powder formulation of the test compound. After two days the plants are infected with a spore 3uspenslon (1.5 x 105 spore3/ml) of the fungus and incubated for 36 hours at 23C and high humidity. Incubation i8 then continued at normal humidity and about 22-23C. Evaluation of fungu3 attack is made 8 days after infection. F~ngu~ attack is 100 % on utreaeed and infected control plants.

Co~pounds of Table l exhibit good activity and inhibit the spread oP the di3ease. Fungus attack i9 reduced to 20 % or less.
xample 3.6: a) Contact action against Nephotettix cinctlceps and Nila-parvata lu~ens (nymphs~
The test is carried out with growlng rice plants. For this purpose 4 plants (14-20 days old) about 15 cm in height are planted into esch of a number of pots (diameter 5.5 cm).

The plants are sprayed on a rotary table with lO0 ml of an aqueous emul-sion preparation containing 400 ppm of the test compound. After the sprly coating has drled, each plant i9 populated with 20 nymphs of the test organisms in the third ~tage. To prevent the cicadas from escaping, a glass cylinder which i9 open at both ands i3 slipped over each of the plants and sealed with a gauze top. The nymphs are kept on the treated plants for 6 day3 until they have resched the adult stage. An evsluation i9 made on the ba~is of percentage mortality 6 days after populatlon of the plants. The test is carried out at about 27C and 60 % relative humi-dity. The plants ara exposed to light for a period of 16 hours per day.

':

`

1 32993~

b) Systemic action against Nilaparvata lugens ~in water~
Rice plants about 10 day3 old (about 10 cm high) are placed in a plastlcs beaker which contains 150 ml of an aqueous emulsion preparatlon of the test compound in a concentration of 100 ppm and i9 closed by a perforated plastics lid. The roots of each of the rice plants are pushed through a hole ln the plastics lid into the aqueous te3t preparation. Then the rice plants are populated with 20 nymphs of Nilaparvata lugens in the N2 to N3 stag~ snd covered with a plastics cylinter. The test i9 carried out st about 26C and 60 % relative humidity, and the plants are e~posed ~o light for a period of 16 hours per dsy. After fi~e days the number of dead test organisms i9 assessed in comparison with untrsated controls. It i9 thus established whether the test substance absorbed via the roots kills she test orga~isms at the upper psrts of the plants.

Compounds of Table 1 exhibit a pronounced killing action on the rice pests both in te~t a) and in test b). The mortality rate i~ 80 % or above. Almost total ~ortality (98-100 %) W8~ achieved with compound~
nos. 1.1, 1.6, 1.14, 1.59, 1.66, 1.87, 1.94, 1.108 and 1.236.

Claims (7)

1. A compound of formula XXI
(XXI) in which, R1 and R2 independently of one another are hydrogen, halogen, C1-C3alkyl, C1-C2haloalkyl, C1-C3alkoxy or C1-C3-haloalkoxy; and R4 is C3-C6cycloalkyl or C3-C6cycloalkyl mono- to tri-substituted by methyl or halogen.

2. A compound according to claim 1 wherein R1 is hydrogen, fluorine or chlorine, R2 is hydrogen and R4 is cyclopropyl, methylcyclopropyl, chlorocyclopropyl or fluorocyclopropyl.

3. A compound according to claim 2 wherein R1 is hydrogen.

4. 2-Anilino-4-formyl-6-cyclopropylpyrimidine.

5. 2-Anilino-4-formyl-6-chlorocyclopropylpyrimidine.

6. 2-Anilino-4-formyl-6-methylcyclopropylpyrimidine.

7. 2-Anilino-4-formyl-6-fluorocyclopropylpyrimidine.