AU601973B2 - Compounds containing triazole or imidazole groups and tetrahydrofuran, use of these as fungicides and processes for the preparation thereof - Google Patents

Description

FORM COM1MO WEALrtH OF AUSTR IALI A PATENTS ACT 1952-1973 COMPLETE SPECFCATION6 0 97 (original) z907 33 PH 1086/1086A% FOR OFICE USE: Cl as 7//7/cP 7 Int. Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority: Related Art: is docume contains The amendmef. ef made urI' i~nt 49 td is cuarct i'.

Nhame of Applicant: Address of Applicant: Actual Inventor(s): Address for Service: RHONE-POULENC AGROCHIMIE 14-20 Rue Pierre Baizet, Lyon 9e, France.

ALFRED GREINER REGIS PEPIN Davies Collison, Patent Attorneys, 1 Little Collins Street, Melbourne, Victoria 3000, Australia ii j Complete Specification for the invention entitled: "COMPOUNDS CrONTAINING TRIAZOLE OR ITIhDAZCLE GROUPS AND TETRAHYDROFUrAN, USE OF THESE AS FUNGICIDES AND PROCESSES FOR THE PREPARATION THEREOF" The following statement is a full description of this invention, including the best method of performing it known to us:- 7- Ir ii ri -la- The present invention relates to new compounds for use in plant protection, to processes for their preparation and to intermediates useful in such processes. It also relates to the use of the new compounds as fungicides, to fungicidal compositions containing them and to use of the compounds for the control of fungal diseases of crops.

Numerous compounds, especially fungicides, 0containing triazole groups are already known, in 0 0* particular, from European Patent Application No. 151,084 oo° which describes compounds of the formula shown'at the end of the description and their use as fungicides. The 0o compounds of the present invention are novel and are not described in European Patent Application No. 151,084.

There is a continuing need for new compounds "o which have improved properties in the treatment of °o fungal diseases or which have an improved spectrum of activity and the applicants have discovered that certain Q 0o new compounds represent, in some aspects of their activities, such an improvement.

o 00 0. 0. The present invention accordingly provides S* compounds of formula depicted hereinafter, wherein: A represents a group Ph-(CH 2 in which Ph is a phenyl ring and m is 0 or 1, preferably 0, Y is a halogen atom or a cyano or nitro group, or an 6ptionaly halogenated alkyl or alkoxy group, n is a positive integer 1,2,3,4 or 5, or zero, the r

J

1 -2groups Y being identical or different when n is greater than 1, Tr represents a 1,2,4-triazol-l-yl group and Im a 1,3-imidazol-l-yl group, R R R 3 R and which may be identical or different, represent a hydrogen atom or a lower alkyl, lower cycloalkyl, aryl (preferably phenyl), aralkyl (preferably benzyl), lower alkoxy, lower alkanoyl or aroyl (preferably benzoyl) radical, these radicals 0 0 10 being optionally substituted (for example, with one or more atoms or radicals such as halogen atoms and lower

O

alkoxy radicals), X and which may be identical or different,each represent a hydrogen atom; a halogen atom; a lower 15 alkyl, lower cycloalkyl, aryl (preferably phenyl) or 00 aralkyl (preferably benzyl) radical, these radicals being optionally substituted as hereinbefore defined for R, to R a Q-R, group in which Q represents 0 or S, and R 20 represents the hydrogen atom or a lower alkyl, lower 0 0 cycloalkyl, aryl (preferably phenyl), aralkyl.

2 (preferably benzyl), lower alkyloyl, aroyl or lower alkylthioyl (preferably acetyl, thioacetyl, propionyl, thiopropionyl or benzoyl); alkoxythioyl, aryloxythioyl or aralkyloxythioyl [the term thioyl corresponds to C radical; these-radicals being optionally substituted as hereinbefore defined for R. to R 5 and R A

-J

I j L I. -3being identical or different when X, and X each represent OR 6 or SR an -NR R 9 group in which R and R which may be identical or different, represent the hydrogen atom or a lower alkyl, lower cycloalkyl, aryl (preferably phenyl) or aralkyl o o° (preferably benzyl) radical, these radicals being 0* optionally substituted as hereinbefore defined for R 0 a j to R 5 or R 8 and R, may together form a divalent hydrocarbon radical, containing from 2 to 6 carbon atoms, one of the carbon atoms being optionally S" replaced by an oxygen, sulphur or nitrogen atom, the divalent hydrocarbon radical itself being optionally substituted (for example with one or more halogen atoms or optionally halogenated lower alkyl or lower alkoxy radicals or a hydroxy radical); S° an N 3 group, provided that X, and X2 do not both o a 3 represent N or X1 and X2 together represent a group of formula wherein Q is as hereinbefore defined and in which R. is a divalent hydrocarbon radical, containing from 2 to 6 carbon atoms, one of the carbon atoms which is not attached directly to Q being optionally replaced by an oxygen or nitrogen atom, the divalent hydrocarbon radical being optionally substituted (for example, with one or more halogen atoms or lower alkyl, lower alkoxy or hydroxy radicals); I- i :-A 1 or X1 and X 2 together represent an =N-R10 group in which R 10 represents a lower alkyl, lower cycloalkyl, aryl (preferably phenyl) or aralkyl (preferably benzyl) radical, or a group of formula OR1. in which R 11 is a lower alkyl, aralkyl or aryl radical, these radicals being optionally substituted as hereinbefore defined for R 1 to R or Rio represents hydroxy; or X and X 2 together represent 0 or S; 0 0 o oo 000000 0 0 o oo 0 00 0 6 0 o 0 000 0 ut o 000 0 t 0 0 0 S00 00000 S0 0 0 0 0 0 i 00 9 9 10 and with the proviso that if X 1 is chosen from the group consisting of hydrogen, a lower alkyl radical, a lower cycloalkyl radical, an aryl radical or an aralkyl radical, X 2 does not represent an atom or radical chosen from that group; salts thereof and addition complexes 15 thereof with metal salts.

The salts according to the invention are preferably acceptable in agriculture and include the hydrochloride, sulphate, oxalate, nitrate or arylsulphonate;. the addition complexes of the compounds of the invention with metal salts are preferably with iron, chromium, copper, manganese, zinc, cobalt, tin, magnesium and aluminium salts. The complexes may be prepared by known methods; for example, zinc complexes may be obtained by reacting a compound of formula I with zinc chloride.

In this specification and the accompanying claims it is to be understood that the adjective lower, when it qualifies an organic radical, means that the radical contains no more than six carbon atoms. Alkyl and alkoxy F I radicals or moieties in this specification may be straight or branched-chain.

The compounds of formula I and compounds which may, if desired, be used as intermediates in the processes for their preparation, and which are described hereinafter, may exist in one or more isomeric forms I o depending on the number of asymmetric centres in the molecule. The invention relates to all the optical o o isomers as well as to their mixtures, in particular 10 racemic mixtures, and to the corresponding diastereoisomers. The separation of the diastereoisomers and/or the optical isomers may be carried out according to :r methods known per se.

Preferred fungicidal compounds of the invention are those of formula I in which Y is a halogen atom and n is 1, 2 or 3.

Compounds of formula I in which n is 1 or 2, and Y is a halogen atom in the ortho and/or para position are especially preferred.

More preferably still, n is 2 and Y is halogen, advantageously chlorine, in the ortho and para positions.

SPreferred compounds of the invention include those of formula I wherein X 2 represents a halogen atom, such compounds being depicted in formula II in which Hal represents a halogen atom, and those of formula I wherein X represents a group -QR 6 such compounds being depicted in formula III.

I- S -6- The triazole compounds of formula II in which Ri,

R

2

R

3

R

4 and R 5 which may be the same or different, each represent a hydrogen atom or a lower cycloalkyl or alkyl group, Hal represents a halogen atom, preferably 5 chlorine or bromine and X 1 represents a halogen, Spreferably chlorine or bromine, or hydrogen atom,and advantageously a hydrogen atom, are especially preferred fungicidal compounds of the invention.

The triazole compounds of formula III in which R R R 3

R

4 and R s represent a hydrogen atom or a lower cycloalkyl or alkyl group, Y, n and m are as hereinbefore defined, X represents a hydrogen atom or an optionally substituted lower cycloalkyl or alkyl group, R represents a hydrogen atom or an optionally substituted' lower cycloalkyl or alkyl group and the other symbols are as hereinbefcre defined, are also preferred fungicidal compounds of the invention.

Preferred triazole compounds of formula II are those in which R R2, R 3

R

4 and R represent a hydrogen 4 20 atom and the halogen atom(s) within the definitions of Hal, X, and X, are the bromine or the chlorine atom.

Preferred triazole compounds of formula III are those wherein R R R 3

R

4 and R 5 represent a hydrogen atom, X 1 represent a hydrogen atom or lower cycloalkyl or alkyl, R 6 represents an optionally substituted lower cycloalkyl or alkyl group and preferably Q represents 0.

According to a feature of the present invention, compounds of formula I wherein X 2 represents a halogen -7atom (ie. compounds of formula II), are prepared by a process which comprises: reacting a haloketone of formula IIa (which may be obtained by a known process) wherein A and R s are as hereinbefore defined and Z represents a halogen atom, with an organometallic compound of formula IIb, wherein M 9^ represents an alkali metal or a magnesium-containing group U (MgHal) or a zinc-containing group (ZnHal) in which Hal O, represents a halogen atom, to obtain a compound of formula 10 IIc wherein the various symbols are as hereinbe ore defined; reacting the compound of formula IIc with an unsubstituted triazole or imidazole in the presence of an organic or inorganic base, for example pyridine, S 15 triethylamine, sodium hydroxide, potassium hydroxide, carbonates and bicarbonates of alkali or alkaline earth metals, and in a solvent such as, for example, an alcohol, ketone, amide, nitrile or optionally halogenated aromatic hydrocarbon to obtain a compound of formula IId wherein the various symbols are as hereinbefore defined; reacting the compound of formula IId with a halogen or a mixed halogen preferably mole for mole, in an inert solvent such as a saturated hydrocarbon or an optionally halogenated aromatic hydrocarbon, to obtain a compound of formula IIe, wherein the various symbols are as hereinbefore defined; cyclization of the compound of formula IIe in -8the presence of an organic or inorganic base preferably at ambient temperature to obtain the compound of formula II.

Step is generally carried out in a solvent, preferably an ether such as diethyl ether or tetrahydrofuran, aliphatic, alicyclic or aromatic r hydrocarbon such as hexane or toluene at a temperature from -50°C to the reflux temperature of the reaction a mixture and in a molar ratio of IIa:IIb which is preferably from 1.1 to 0.2. The reaction leads to the compound of formula IIc after neutralization of the reaction medium.

Step is preferably carried out at a temperature of from 80 0 C to the reflux temperature of the reaction mixture and in a molar ratio of IIc:imidazole or triazole which is preferably from 1.1 to 0.2, to obtain the compound of formula IId. The reaction generally passes through an epoxide intermediate of formula IIh i which may, if desired, be isolated or prepared separately by known methods.

In step the organic or inorganic base is, for example, a base listed in step b in a molar ratio of 'i compound II:base which is preferably from 1.1 to 0.66: the reaction may be carried out in a protic or aprotic solvent (eg. water, alcohol, ketone, nitrile, ester, saturated or optionally halogenated aromatic hydrocarbon, dimethyl sulphoxide or amide such as dimethylformamide).

A modification of the process described above for i 1 -9the preparation of the compounds of formula I wherein X represents a halogen comprises carrying out stage (b) after stage using the same reaction conditions for the different stages. Thus, the compound of formula IIc I 5 is reacted with a halogen or halogen halide (mixed halogen) in an inert solvent to obtain a compound of formula IIf, the compound of formula IIf is then cyclized in the presence of an organic or inorganic base to obtain the compound of formula IIg, and the compound of formula 10 IIg is then reacted with an unsubstituted triazole or Simidazole group to obtain the compound of formula II.

According to a further feature of the invention compounds of formula I wherein X represents QR and X is other than Hal (compounds of formula III), are prepared 15 by the reaction of a compound of formula II or IIg with a I heteroatomic nucleophile of formula R in which R, and Q are as hereinbefore defined and E is a cation, for example an alkali or alkaline earth metal or a quaternary ammonium cation in the presence of a base and, optionally, a phase transfer catalyst and, when a compound of formula IIg is used as starting material, reaction of the compound of formula IIIa obtained with an unsubstituted triazole or imidazole. The reaction is generally carried out in a suitable solvent and at reaction temperatures which are generally from -30 0 C to the reflux temperature of the reaction mixture and in 6 molar ratio III:R 6 QE which is preferably from 1.2 to 0.1.

r I i- According to a further feature of the invention compounds of formula III wherein R is an optionally monoor polyhalogenated lower alkyl group, are prepared by reacting a compound of formula III or IIIa wherein R 6 represents a hydrogen atom with an alkyl halide containing one or more halogen atoms in the presence of an organic or inorganic base and, when a compound of formula IIIa is l used as starting material, by reaction of the compound obtained with an unsubstituted triazole or imidazole. A molar ratio of III or IIIa:halide from 1.1 to 0.2 is generally used.

According to a further feature of the invention compounds of formula I wherein X represents a hydroxy group compounds of formula III in which Q represents the oxygen atom and R 6 the hydrogen atom), are prepared by the reaction of a compound of formula II or IIg with a metal (preferably an alkali metal or alkaline earth metal) hydroperoxide, hydroxide, oxide or superoxide. The reaction with the metal compound is generally carried out 20 in the presence of an inert organic solvent, at a Stemperature from -30° to the reflux temperature of the reaction mixture, in a molar ratio which is preferably from 1.1 to 0.2.

According to a feature of the invention compounds of formula I wherein X 2 represents N 3 are prepared by the reaction of a compound of formula II or IIg with an alkali metal or ammonium azide, preferably in a molar ratio o.f i identical or different, represent the hydrogen atom or a lower cycloalkyl, aryl or aralkyl 73 -11from 1.1 to 0.2, preferably in an aprotic solvent, at a temperature of from -300 to the reflux temperature of the reaction mixture and, when a compound of formula IIg is used, reaction of the compound thus obtained with an unsubstituted imidazole or triazole. When X 2 in formula I represents an alkoxythioyl, aryloxythioyl or aralkyloxythioyl group, the compounds of formula IIg or II are reacted with an a 1 ali metal or ammonium xanthate and, when a compound of formula IIg is used, the compound thus obtained is reacted with an unsubstituted triazole or imidazole.

According to a further feature of the invention compounds of formula I wherein X represents a hydroxy group, are prepared by the reaction of a compound of formula IIc or IId with a peroxide to obtain, respectively, an epoxide of formula IIIb or IIIc, hydrating the epoxides to obtain, respectively, the triols of formula IIId or IIIe, cyclising the triols in the presence of a dehydratinc agent such as hydrochloric, hydrobromic, sulphuric or sulphonic acids, to obtain, respectively, the compounds of formula IIIa or III and reacting the compound of formula IIIa with an unsubstituted triazole or imidazole. The dehydration is carried out, if appropriate in a protic or aprotic solvent. Optionally, if necessary, the alcohol group may be protected in a manner known per se for compounds of formula IIId and IIIe.

L orX 1 orXz together represent =0 or =S; and with the proviso that if X, is chosen from the i-I-III I- r-l- -12- Compounds of formula I wherein X 2 represents a hydroxy group may be prepared by the reaction of a compound of formula II or IIg with an alkali metal or alkaline earth metal carboxylate, especially sodium benzoate, in the presence of a phase transfer catalyst and optionally in the presence of an aprotic polar inert I t< solvent, if required in the presence of water, and at temperatures of from 00 to the reflux temperature of the Sreaction mixture and, when a compound of formula IIg is used, reaction of the compound thus obtained with an unsubstituted triazole or imidazole.

Compounds of formula I wherein X and X together represent =0 (compounds of formula IV wherein X represents the oxygen atom), are prepared by the oxidation of a compound of formula IIIa or III in which QR represents hydroxy and X represents hydrogen, to obtain a compound of formula IV or IVa and, when a compound of formula IIIa is used as starting material, reaction of the compound obtained with an unsubstituted triazole or imidazole. The gem-halogenated compounds (X =X =Hal) of formula I are prepared by reacting a phosphorus pentahalide with a corresponding ketone (a compound of formula IV or IVa in which X 1 represents an oxygen atom), optionally in the presence of an inert aprotic solvent and optionally in the presence of a quaternary ammonium halide, preferably at ambient temperature, and when the starting material is a compound of formula IVa, reaction S I j -13-

I

i i St I9 St S

'S

I

Str of the compound obtained with an unsubstituted triazole or imidazole.

The compounds of formula I wherein X and X 2 together represent =S (compounds of formula IV wherein X, represents the sulphur atom) are prepared by the thionation of a compound of formula IV or IVa wherein X1 and X 2 together represent for example, with H 2 S or

P

2 S in a molar ratio which is preferably from 1.1 to 0.2, in the presence of an inert organic solvent (pyridine or 10 hydrocarbon, for example) at a temperature of from 20° to the reflux temperature and, when the starting material is a compound of formula IVa, reaction of the compound obtained with an unsubstituted triazole or imidazole.

The compounds of formula I wherein X, and X 2 simultaneously represent QR 6 (ie. a compound of formula V) are prepared by the reaction of a compound of formula IV or IVa in which X and X 2 together represent =0 or -S with a compound of formula HQR 6 wherein Q is O or S in a molar ratio which is preferably from 1.1 to 0.2, in the presence of an acid catalyst and in a suitable solvent, which may be the alcohol or thiol itself, or an inert solvent such as hydrocarbons or alcohols and, when the starting material is a compound of formula IVa, reaction of the compound obtained with an unsubstituted triazole or imidazole.

Compounds of formula I wherein X and X 2 together represent -Q-R and R 7 is as hereinbefore defined may

A:

e -14be prepared by the process described for the preparation of compounds of formula I wherein X and X 2 simultaneously represent QR 6 by using a compound HQ-R7-QH instead of

HQR

6 Compounds of formula I wherein X represents NR are prepared by reacting a compound of formula II or IIg with an amine of formula P--NR R generally in a molar ratio from 1.1 to 0.2, optionally in the presence of I: another organic or inorganic base to obtain a compound of S 10 formula VI from the compound of formula II and a compound of formula VIa from the compound of formula IIg and, when a compound of formula IIg is used as starting material, reacting the compound obtained with an unsubstituted triazole or imidazole.

Compounds of formula I wherein X and X 2 together represent N-R 0 (ie. a compound of formula VII), are prepared by reacting a compound of formula IV or IVa with an amine of formula Rio-NH 2 or a salt thereof in a molar ratio which is preferably from 1.1 to 0.2, generally in an inert organic solvent and, when a compound of formula IVa is used as starting material, reacting the compound (of formula VIIa) thus obtained with an unsubstituted imidazole or triazole.

Compounds of formula I wherein X and X 2 together represent =N-RI 0 in which Ro represents a group OR11 wherein R 1 represents an optionally substituted aralkyl or lower alkyl-radical are prepared by the reaction of a 6-! compound of formula VII in which R 10 represents a hydroxy radical with an alkylating agent of formula R,,D in which

R

1 1 is an optionally substituted aralkyl or lower alkyl radical and D represents, as a leaving group, a halogen, sulphonium, ammonium, sulphonate or sulphate group, in the presence of an organic or inorganic base, in order to obtain the oxime substituted on the oxygen.

The invention also relates to compounds which can be used as intermediates in the preparative processes described above: the compounds of formula II, IIc, IId, lie, IIf, IIg, IIh, III, IIIa, IIIb, IIIc, IIId, IIIe, IV, IVa, V, Va, Vb, VI, Via, VII and VIIa in which Ri to R Y, Tr, Im, m, n, X X2, Q, Hal and Z are as hereinbefore 0* defined are novel and as such constitute features of the S 15 invention.

The present invention also relates to the use of the compounds of formula I as fungicides.

The compounds according to the invention may be used for the preventive as well as curative control of fungi, especially of the basidiomycetes, ascomycetes, adelomycetes or fungi imperfecti, in particular rusts, mildew, cercosporella diseases, fusarium diseases, Shelminthosporium diseases, septoria diseases and rhizoctonia diseases of crops and of plants in general and, in particular, of cereals such as wheat, barley, rye, oats and their hybrids and also rice and maize. The compounds according to the invention are active, in particular, against fungi, especially of the S* basidiomycetes, ascomycetes, adelomycetes or fungi 4' 30 imperfecti type such as Botrytis cinerea, Erysiphe graminis, Puccinia recondita, Piricularia oryzae, Cercospora beticola, Puccinia -16 strilformis, Erysiphe cichoracearum, Fusarium oxysporum (meLonis), Pyrenophora avenae, Septoria tritici, Venturia inaequaLis, WhetzeLinia scLerotiorum, MoniLia Lixa, MycosphaereLLa fijiensis, Marssonina panettoniana, Alternaria soLani*, AspergiLLus niger, Cercospora arachidicola, CLadosporium herbarum, HeLminthosporium oryzae, PeniciLLium expansul, Pestalozzia sp., PhiaLophora cinerescens, Phoma betae, Phoma foveata, Phoma Lingam, Ustilago maydis, VerticiLLium dahLiae, Ascochyta pisi, Guignardia bidweLLii, Corticium roLfsii, Phomopsis viticoLa, ScLerotinia sciero- 0 tiorum, Scierotinia minor, Coryneum cardinaLe and Rhizoctonia soLani.

They also possess activity against the following fungi: AcrostiLagmfus koningi, the Alternaria, the CoELetotrichum, Corticium roLfsii, Diplodia natalensis, Gaeumannomyces graminis, GibbereLLa fujikuroi, Hormodendron cLadosporioides, Lentinus degener or tigrinus, Lenzites quercina, PemnonieLLa echinata, Myrothecium verrucaria, PaecyLomyces varioti, PeLLicuLaria sasakii, PheLLinus megaLoporus, PoLystictus sanguineus, Poria vaporaria, ScLerotium roLfsii, Stachybotris atra, the Stereu,, StiLbum sp., Trametes trabea, Trichoderma pseudokoningi and Trichothecium roseum.

The compounds of the invention are of special interest because of their broad spectrum as regards cereal diseases (mildew, rust, eyespot, net blotch, Leaf spot and foot rot). They are also of speciaL interest because of hydroxy radicals); i-- 17 their effectiveness against grey mould (Botrytis) and cercospora diseases and, because of this, they may be applied on crops as varied as grape vine, vegetable crops and tree crops and tropical crops such as peanut, banana, coffee, pecan nut and others.

In addition to the apptications already described above, the products according to the invention additionally have an excellent biocidal activity with respect to many other kinds of microorganisms, among which there may be mentioned fungi such as those belonging to the genera: PuLLularia such as the species P. pullulans, Chaetomium such as the species C. gLobosum, Aspergillus such as the species Aspergillus niger, Coniophora such as the species C. puteana.

Owing to their biocidal activity, the products of Sthe invention make it possibLe to controL effectiveLy microorganisms whose proLiferation gives rise to numer- 4 ous problems in the agricultural and industrial fields.

To this end, they are particularly weLL suited for the protection of plants or of industrial products such as wood, Leather, paints, paper, ropes, plastics and industrial water circuits.

They are particularLy well suited for the protection of Lignocellulose products and especially of wood, whether it is timber for furniture or construction, or timber which is exposed to bad weather such as timber for II 18 o c~c~0 8884fl0 8 0 o 8Q 88 8 0 80 04n888 8 888 fencing, vine stakes or railway sleepers.

The compounds according to the invention, used on their own or in the form of compositions as defined above in the treatment of wood, are generally employed with organic solvents and may, if desired, be used in combination with one or more known biocidal products such as pentachlorophenol, metal salts, especially copper, manganese, cobalt, chromium or zinc salts derived from inorganic or carboxylic acids (heptanoic, octanoic or naphthenic acids), organic complexes of tin, mercaptobenzothiazole, and insecticides such as pyrethroids or organochlorine compounds.

Finally, they have an excellent selectivity with respect to crops.

15 They are advantageously applied at doses of 0.005 to 5 kg/ha, and more specifically 0.01 to kg/ha.

In practical use, the compounds according to the invention are rarely used alone. Most often they form part of compositions. The present invention provides compositions which may be used, inter alia to protect plants against fungal diseases, or in plant growth regulating compositions, which comprise, as active ingredient a compound of general formula I or a salt thereof or an addition complex thereof with a metal salt in association with an agriculturally acceptable carrier. The compositions generally also comprise an agriculturally acceptable? surfactant. Conventional inert carriers and conventional surfactantE can be used.

84 o 8 A 880 8 00 8 8 8 9 88 88*8 8888 848814 4 48 4 8 8 19 The term "carrier", in the present description, denotes a natural or synt'hetic,organic or inorganic material, with which the active substance is combined in order to facilitate its application to the plant, to seeds or to the soiL. Therefore, this carrier is generaLLy inert and it must be acceptable in agricu'ture, especiaLLy on the treated plant. The carrier may be soLid(e.g. clays, natural or synthetic silicates, silica, resins, waxes and solid fertilizers,) or liquid water, alcohols, ketones, petroleum fractions, aromatic or paraffinic hydrocarbons, chlorinated hydrocarbons and liquefied gases).

The surfactant may be an emulsifier, dispersant or wetting agent of ionic or non-ionic type. For example, there may be mentioned poLyacrylic acid salts, lignosulphonic acid salts, phenolsulphonic or naphthalenesulphonic acid salts, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols (especially alkylphenols or arylphenoLs), sulphosuccinic acid ester salts, taurine i0 derivatives (especially alkyltaurates), phosphoric esters of alcohols or of polycondensates of ethylene oxide with phenols. The presence of at least one surfactant is generally indispensable when the active substance and/or the inert carrier are insoluble in water and the vector agent for the application is water.

Therefore, for their application, the compounds of formula are generally in the form of compositions; 20 these compositions according to the invention are themselves in fairLy diverse sbLid or Liquid forms.

As soLid forms of compositions, there may be mentioned powders for dusting or scattering (with a content of the compound of formuLa u- to 100%) and peLLets, especially those obtained by extrusion, by comipacting, by impregnation of a granulated carrier, or by granuLation starting from a powder (the content of the compound of formula in these peLLets being from 1 to 80% in these Latter cases).

As Liquid forms of compositions, or forms intended to constitute Liquid compositions when appLied, there may be mentioned soLutions, especiaLLy water-soLuble concentrates, emuLsifiable concentrates, emulsions, fLowabLes, aerosaLs, wettabLe powders (or powder for spraying) and i pastes.

The emuLsifiabLe or soLubLe concentrates most frej quentLy contain 10 to 80% of active substance, whereas the i emuLsions or soLutions ready for appLication contain, for '0i their part, 0.01 to 20% of active substance.

These compositions may aLso contain other types of ingredients such as, for exampLe, protective coLLoids, adhesives, thickeners, thixotropic agents, penetrants, stabiLizers and sequestering agents, as well as other known active substances with pesticidal properties (especiaLLy insecticidal or fungicidal properties) or properties which promote pLant growth (especiaLLy

-S*

~rrrrr~~i;e 21 fertilizers) or plant growth regulating properties. More generally, the compounds according to the invention may be combined with solid or liquid additives which correspond to the usual techniques of formulation.

For example, in addition to the solvent, the emulsifiable concentrates may contain, when necessary, 2 to 20% of suitable additives such as the stabilizers, surfactants, penetrants, corrosion inhibitors, colouring agents or adhesives mentioned above.

10 In the case where the compounds according to the 0 4 invention are used as fungicides, the doses to be used may a +4 vary within broad limits according, in particular, to the virulence of the fungi and the climatic conditions.

In general, compositions containing 0.5 to 5,000 ppm of active substance are very suitable; these values apply to the compositions ready for application.

Ppm denotes "parts per million". The range from 0.5 to 5,000 ppm corresponds to a range from 5 x 10 to (percentages by weight).

1, 0 As regards compositions which are suitable for storage and transportation, they more advantageously contain from 0.5 to 95% (by weight) of active substance.

Thus, the compositions for agricultural use according to the invention may contain the active substances according to the invention within very broad Limits, ranging from 5.10-5% to 95% (by weight).

By way of example, the compositions of some

I'~

jL t; jl i

I

r m i I-l; *-urrwlr(u~iLi

Y.

44 I, 4 4 4s 4s 0 44 4 ci4 0444* 4.

44 14l 22 concentrates are given below: unless otherwise specified percentages are by weight.

Example F (formuLation) 1 Active substance 400 g/Litre Alkali metaL dodecyL benzenesulphonate 24 g/Litre 10:1 ethylene oxide/nonylphenol condensate 16 g/litre CycLohexanone 200 g/litre Aromatic solvent q.s. 1 Litre According to another formula for an emulsifiable 10 concentrate, the following are used: Example F 2: Active substance 250 g Epoxide-treated vegetable oil 25 g Mixture of alkylarylsulphonate, polyglycol ether and fatty alcohpo s 100 g Dimethylformamide 50 g Xylene 575 g From these concentrates, by dilution with water, it is possible to obtain emulsions of any desired concenwhich are especially suitable for application on leaves.

Flowables, which can also be applied by spraying, are prepared so as to obtain a stable fluid product which does not settle; they usually contain from 10 to 75% of substance, from 0.5 to 15% of surfactants, from 0.1 to 10% of thixotropic agents and from 0 to 10% of suitable additives such as antifoams, corrosion inhibitors, stabilizers, penetrants and adhesives, and, as a carrier, water i d 23 or an organic Liquid in which the active substance is of Low solubility or insolubLe: solid organic substances or inorganic saLts may be dissolved in the carrier to assist in preventing sedimentation, or as anti-freezes for the water.

The wettable powders (or' powder for spraying) are usuaLLy prepared so as to contain 20 to 95% of active substance, and they usuaLLy contain, in addition to the soLid Scarrier, from 0 to 5% of a wetting agent, from 3 to 10% of 10 a dispersant, and, when necessary, from 0 to 10% of one or 0 S"more stabiLizers and/or other additives such as penetrants, adhesives, anti-caking agents or colouring agents.

I By way of exampLe, various compositions of wetta'bLe powders are given beLow: ExampLe F 3: Active substance CaLcium LignosuLphonate (defLoccuLant) IsopropyL naphthalenesuLphonate (anionic wetting agent) 1% 0 Anti-caking siLica KaoLin (filler) 39% Another composition of powder for spraying, at strength, uses the foLLowing constituents: Example F 4: Active substance 700 g Sodium dibutyL naphthaLenesuLphonate FO g Condensation product of naphthaLenesuLi l•IfIII

I

24 phonic acid, phenoLsuLphonic acid and formaLdehyae in proportions 3:2:1 KaoL in 100 Whitener 120 Another composition of powder for spraying, strength, uses the foLLowing'constituents: Example F Active substance 400 Sodium LignosuLphonate 1 l Sodium dibutyLnaphthaLenesuLphonate SiLica 540 Another composition of powder for spraying, strength, uses the following constituents: Example F 6: Active substance 250 CaLcium LignosuLphonate Mixture of whitener and hydroxyethyLceLLuLose in equal parts by weight 19 Sodium dibutylnaphthaLenesuLphonate SiL ica 195 Whitener 195 Kaolin 281 Another composition of powder for spraying, strength, uses the foLLowing constituents: Example F 7: Active substance 250 IsooctyLphenoxy-poLyoxyethyLene-ethanoL 25 g g 25 Mixture of whitener and hydroxyethylceLLuLose in equal parts by weight 17 Sodium aluminosilicate 543 KieseLguhr 165 Another composition of powder for spraying, strength, uses the following cons'tituents: Example F 8: Active substance 100 Mixture of sodium salts of sulphates of saturated fatty acids 30 Condensation product of naphthaleneg g suLphonic acid and formaldehyde 50 g Kaolin 820 g To obtain these powders for spraying or wettable powders, the active substances are intimately mixed in suitable -ixers with the additional substances, and the mixtures are ground in mills or other suitable grinders.

Powders for spraying are thereby obtained, the wettability and suspendabiLity of which are advantageous; they may be suspended in water at any desired concentration and these suspensions may be very advantageously used, especially for application on plant leaves.

Instead of the wettable powders, pastes can be produced. The conditions and means of production and use of these pastes are similar to those for wettable. powders or powders for spraying.

As already stated, the dispersions and aqueous 26 emulsions, for example the compositions obtained by diluting with water a wettable powder or an emuLsifiabLe concentrate according to the invention, are included within the general scope of the present invention. The emuLsions can be of the water-in-oil or oiL-in-water type, and they may have a thick consistency Like that of "mayonnaise" 0 0 0 4 00 44t Granulates intended for placing on the soil are usually prepared so as to be between 0.1 and 2 mm in size, and they may be manufactured by agglomeration or impregnation. In general, the granulates contain 0.5 to 25% of active substance and 0 to 10% of additives such as stabilizers, slow-release modification agents, binders and solvents.

i 'i s

I;

-According to an example of a.granulate composition, the following constituents are used: Example F 9: Active substance 50 g Epichlorohydrin 2.5 g Cetyt polyglycol ether 2.5 g Polyethylene glycol 35 g Kaolin (particle size: 0.3 to 0.8 mm) 910 g.

In this particular case, the active substance is mixed with epichlorohydrin and dissolved in 60 g of acetone; polyethylene glycol and cetyl polyglycol ether are then added. The kaolin is wetted with the solution obtained and the acetone is then evaporated under vacuum.

I; i r

C

W,

-27 A microgranulate of this type is advantageously used to control soil fungi.

The compounds of formula may also be used in the form of powders for dusting; a composition containing 50 g of active substance and 950 g of talc can also be used; a composition containing 20 g of active substance, g of finely divided silica and 970 g of talc may also be used; these constituents are mixed and ground, and the mixture is applied by dusting.

Examples I to VII illustrate particular methods of preparing the compounds according to the invention as well as the compounds themselves.

Example I: Preparation of 1-C4-bromo-2-(2,4-dichlorophenyl)tetrahydrofuran-2-ylmethyl]-1H-1,2,4-triazole.

Compounds Nos. la,1b and la Ib Stage a) Preparation of 1-chLoro-2-(2,4-dichlor6phenyL) 4-penten-2-ol: An organomagnesium derivative is prepared by adding a solution of allyl bromide (110 cc) in ethyl ether (70.0 cc) and tetrahydrofuran (200 cc) with magnesium S(110 between 15 and 200C, over three hours. The mixture is refluxed for 30 min and decanted, and the residue is washed with ether.

A solution of aLpha,2,4-trichLoroacetophenone i 28 (175 g) in tetrahydrofuran (250 g) at -30 0 C is added to this organic phase and the mixture is neutraLized with acetic acid. This is washed with water, dried over sodium suLph.ate, concentrated and then distilled under vacuum. A coLourLess oil is obtained (205 B.p. (3.10-2mm Hg).= 140-1420C.

Stage b) Preparation of 1-C2-(2,4-dichLorophenyL)-2hydroxypenten-4-yl]-1H-1,2,4-triazoLe A mixture of the product obtained in stage a) (106 triazoLe (55 g) and potassium carbonate (160 g) is heated in dimethyLformamide (600 cc) at 1200 for four hours. The insoLubLe materials are fiLtered and washed with dimethyLformamide, and the reaction mixture is concentrated under vacuum. The residue, dissolved in methyLene chloride, is washed with water and then concentrated. The product is obtained by crystaLLization in ethyl acetate after dilution with heptane. A paLe pink solid, m.p. 1010, is isolated (97 g).

Stage c) Preparation of the compounds No. la and No. lb The compound obtained in stage b (35 g) in chlorqform (200 cc) is treated with bromine at 00. After decoLorizing, the solvent is evaporated and the residue redissoLved in methanoL. An aqueous solution of potassium hydroxide is then added until a basic pH is obtained.

After evaporating the medium under vacuum, the residue is extracted with ethyL acetate, washed with water and concentrated. The oil obtained (40 g) consists of a mixture -i

_LI^_I_

t i i: 29 of two diastereoisomers in substantially equal proportions. Using silica column chromatography, the Least polar isomer No. la: white crystaLs m.p. 830, and then the most polar isomer No. Ib: white crystals m.p. 940, are isolated in sequence. After recrystallization, la, m.p. 960 and Ib, m.p. 1040, are obtained. The 50:50 mixture of la and lb has a melting point of 740.

The following compounds were prepared in the same way, using 'he appropriate raw materials: 1-[4-bromo-2-(4- 10 chLorophenyl)tetrahydrofuran-2-ylmethyL)-1H-1,2,4-triazoLe: 1c: m.p. 740; Id: m.p. 780 and Ic+d: m.p. 690 Example II Preparation of 1-C2-(2,4-dichlorophenyl)-4hydroxytetrahydrofuran-2-yLmethyl]-1H-1,2,4-triazoLe.

o a .c a I 0 Compounds No. 2a and No. 2b.

The isomer (10 g) la of Example I, which is the least polar isomer, dissolved in chLorobenzene (30 cc), is refluxed for 48 h, in the presence of sodium benzoate g) in water (30 cc), and the phase transfer catalyst "ADOGEN 464" methyltriaLkyLammonium chloride (1g).

After diluting with ether, the organic phase is washed with water and reduced under vacuum. The residue is then treated with methanol (100 cc) in the presence of potassium hydroxide (7 g) at reflux temperature for 3 hours.

The mixture is cooled, diluted with water and extracted with ethyl acetate, and the product washed to neutrality and purified by chromatography, the crude product being obtained after concentration under vacuum. The alcohol 2a is t~ i

I

isolated in the form of a white powder (2.8 m.p. 193° I Operating in the same way, starting from the most poLar isomer lb obtained according to ExampLe I, the opticaLLy active alcohol 2b is obtained in the form of a white powder, m.p. 162°C. The 50:50 mixture of 2a and 2b is an oil.

Example III Preparation of 1-C2-(2,4-dichlorophenyL)-4ethoxytetrahydrofuran-2-ylmethyL]-1H-1,2,4-triazole.

Compounds No. 3a and No. 3b.

S 10 The aLcohoL 2a (2.2 g) dissolved in dimethyLsulphoxide (12 cc) is treated, in sequence, with 80% strength sodium hydride (0.42 g) and then with ethyl iodide (1.15 cc). After 15 minutes, the medium is diluted with water and extracted with ethyL acetate.- After washing with water, the solvent is evaporated and the residue is purified by silica column chromatography to obtain a colourless oil which is the isomer 3a which crystallizes on trituration with pentane m.p. 900; in the same way, starting with 2b, the isomer 3b, which is a white powder, m.p. 630, is obtained. The 50:50 mixture of 3a 3b is an oil. The compounds of formula VIII listed in the following table were obtained in the same way, using the appropriate alkyl halide or acid: i i Ii ii 31 No. X X, Melting Point 4a H 0-C-4 (phenyl) 98 0 4b OC-# (phenyl) H 140 0 H OCH 3 oil 0-CH H oil 6a H O-n-Pr oil 6b 0-n-Pr H oil 0 0 0 0~ 4 c-r n Example IV Preparation of 1-[2-(2,4-dichLorophenyL)-4ethyLthiotetrahydrofuran-2-yLmethyL]-1H-1,2,4-triazoLe.

Compounds No. 7a and No. 7b The bromide la (3.8 g) dissoLved in dimethyl suLphoxide (38 cc) containing water (2 cc) is treated with sodium hydrogen sulphide (2.8 g) for 2 hours. Powdered potassium hydroxide (3.3 g) is then added, foLLowed by ethyL iodide (4 cc). After 10 minutes of stirring, the medium is diluted with water and extracted with ether.

20 After drying and evaporation, the isomer 7a, which is a yeLLow oil (3.9 m.p. 880, is obtained.

Operating in the same way, starting with Ib, 7b is obtained in the form of a paLe yeLLow powder, m.p. 640 The mixture of isomers is an oiL. The compounds of formuLa 25 VIII Listed in the foLlowing tabLe were obtained in the same way, using the appropriate thiols:

A

i 32 k( 4t t i 4110

I

44 i No. X X2 Melting point 8a H S-CH 3 96 8b S-CH 3 H oiL 9a H S-n-Pr 110 ;9b S-n-Pr H oil H S-2-CLEt 127 S-2-CLEt i H oiL 11a H S-i-Bu 68 11b S-i-Bu H oil 12a H S-i-Pr 12b S-i-Pr H Example V Preparation of 1-C8-(2,4-dichlorophenyl)- 1,4, 7-trioxaspiroC4.4]nonan-8-ylmethyl]-1H-1,2,4-triazole.

Compound No. 13 Stage a) Preparation of 1-chloro-2-(2,4-dichLorophenyL)- 3,4,5-pentanetriol.

The chlorohydrin obtained in stage a) of Example I (91 g) is epoxidized in 1,2-dichloroethane (125 cc) in the presence of vanadyl acetylacetonate (5 g) and 70% strength tert-butyl peroxide (200'cc) by heating at the reflux temperature for 48 hours. The cooled medium is diluted with water, washed several times with a sodium bisulphite solution and then concentrated. The residue is then converted 1;

A

iL~-

~I

33 Cr C Cr C cCr

'CC

A.

to triol by heating in water (200 cc) and dioxane (200 cc) in the presence' of perchLoric acid (5 cc) for 3 hours.

After dilution with water, the medium is extracted with toluene (300 cc) and then concentrated.

Stage b) Preparation of 2-(2,4-dichLorophenyl)-2-chloromethyLtetrahydrofuran-4-one' The oily residue obtained in stage a) is then heated in toluene (100 cc) and butanoL (200 cc) in the presence of paratoLuenesuLphonic acid (0.5 with the 10 separation of the water formed. After evaporating the reaction medium, the residue is chromatographed on a silica column (40:60 ethyl acetate/heptane eLuant) to obtain a colourless oil (14.5 g) corresponding to a mixture of alcohol diastereoisomers, namely 2-(2,4-dichlorophenyL)- 4-hydroxy-2-chLoromethyltetrahydrofuran. This product is directly oxidized with chromic anhydride in acetic acid to obtain, after purification by silica column S chromatography, furanone in the form of white crystals, m.p. 990C.

Stage c) Preparation of 7-chloromethyl-7-(2,4-dichlorophenyt.)-1,4,6-trioxaspiroC4.4]nonane.

The furanone obtained in stage b) (4.2 in toluene (50 cc), is heated at reflux temperature in the presence of ethylene glycol (6.5 cc.) and p-toluenesulphonic acid (0.1 with the separation of the water formed, until the disappearance of the starting product.

The medium -is washed with sodium hydroxide and

CC~

1 C t t 1) 34 then diluted with water, extracted with ether and concentrated. A white solid (5.1 m.p. 990, is obtained.

Stage d) Preparation of compound 13 The halide of stage c) (5 g) in dimethyl suLphoxide (20 cc) is heated to 1700 in the presence of triazoLyL sodium (2.75 g) for 6 hours. The medium is poured into water, extracted with ethyl acetate, concentrated and purified by silica column chromatography. After recrystallization in an ethyl acetate/heptane mixture, paLe yellow crystals (3.6 m.p. 1230, are isolated.

Example VI Preparation of 1-[4-chLoro-2-(2,4-dichLoroo phenyl)-tetrahydrofuran-2-yLmethyl]-1H-1, 2 ,4-triazoLe.

Compounds No. 14a and No. 14b Stage a) Preparation of 2-(2,4-dicblorophenyL)-1,4,5trichloro-2-pentanol.

The chlorohydrin obtained in stage a) of Example I dissolved in dichloromethane (150 cc) is treated with gaseous chlorine (13.4 g) at -150. The medium is then treated with a 37% strength sodium bisulphite soLution (15 cc), washed with water, dried and then evaporated.

A crude product in the form of a colourless oil (49.7 g) containing approximately 70% of the desired product in the form of a mixture of two diastereoisomers is obtained.

Stage b) Preparation of 1-(2,4-dichLorophenyL)-1-(2,3dichLoro-1-propanyl)oxirane A first method consists in dissolving the crude chlorohydrin (10.3 g) obtained in stage a) above in 35 methanoL (30 cc) and treating it with a solution of methanoLic potassium hydroxide (12 cc) at a concentration of -3 2.55 x 10 moLes/Litre, at ambient temperature. The precipitate is filtered and the methanolic solution is evaporated under vacuum. The residue is purified by silica column chromatography. A colourless oil is obtained (7.4 g).

A second method consists in dissolving the chlorohydrin (19.9 g) obtained in stage a) of Example I in methanol (75 cc), and treating it with a potassium hydroxide (4.9 g) solution in methanol (20 cc) at ambient temperature. After the filtration of the insoluble material and evaporation, epoxide (17.1 g) is obtained in the form of a yellow oil. This epoxide is treated with chlorine 0 a until the yellow colour (10.1 g) pe.rsists at -15°C. The medium is then washed with a sodium bisulphite solution followed by water, and then evaporated under vacuum. A yellow oil (20.8 g) consisting of a mixture of two diastereoisomers in a ratio of 45:55 is obtained.

Stage c) Preparation of 1-[4-chloro-2-(2,4-dichlorophenyl) tetrahydrofuran-2-ylmethyl]-1H-1,2,4-triazoLe The epoxide obtained in stage b) (61.7 g) in 1butanol (0.5 litre) is heated at 900 for 6 hours in the presence of triazolyl sodium (18.6 The inorganic precipitate is filtered and the butanol is evaporated. The residue is purified by silica column chromatography (48% ethyl acetate:48% heptane:4% methanol eluant) to obtain, in sequence, the first diastereoisomer 14a, 1130, and -7 'lv

I

36 then the second diastereoisomer 14b, m.p. 970. The 50:50 mixture of 14a 14b has a melting point of 900 Example VII Preparation of 1-C4-oxo-2- 2,4-dichLorophenyL)tetrahydrofuran-2-ylmethyl]-1H-1,2,4-triazoLe. Compounds 15 and 20 1 0 0 0 0 000 0oo 00 400 The alcohol 2a (37.7 g) is added at -60°C to a solution of dimethyl sulphoxide (17 cc), in dichLoromethane (120 cc), treated at -600 with a solution of trifLuoroacetic anhydride (25.4 cc) in dichLoromethane (60 cc).

10 After maintaining at -600 for half an hour, the temperature o is allowed to rise to ambient temperature and triethyLamine S (48 cc). The medium is poured into water, extracted with dichLoromethane and evaporated. A white powder 910) is isolated by crystallization in ether.

A mixture of ketone 15 (3.1 phosphorus pentachLoride (2.3 g) and dichLoromethane (30 cc) containing triethylbenzylammonium chloride (0.25 g) is stirred for 2 hours at ambient temperature until the starting material disappears. The medium is evaporated, diluted with water (100 cc), neutralized with sodium bicarbonate and extracted with ether. After drying and evaporation, the oily residue is recrystallized in isopropyL ether (twice). A white powder (0.6 m.p. 1380, is obtained. 1-C4,4-dichloro-2- (2,4-dichLorophenyl)tetrahydrofuran-2-ylmethyl-iH-1, 2 4 triazole, compound No. 37 ExampLe VIII Preparation of 1-C4-dimethyLamino-2-(2,4dichloropheny )tetrahydrofuran-2-ylmethyl]-1H-1,2,4j triazole. Compound 16 The ketone of example III and then sodium cyano- S 5 borohydride (0.24 g) are successiveLy added to a solution of potassium hydroxide (0.24 g) and dimethylamine hydrochloride (1.05 g) in methanol. After 15 hours, the medium is diluted with water and extracted with ether. The desired product is then extracted from the organic phase with 6N hydrochLoride acid (3 x 20 mL). After neutralization, ex- Straction and siLica column chromatography, compound No. (1.6 g) is isolated in the form of a pale yellow oil (50:50 mixture of 2 isomers).

Example IX Preparation of 1-C4-methoxyimino-2-(2,4dichlorophenyl)tetrahydrofuran-2-yLmethyl]-1H-1,2,4triazole. Compound 17.

The ketone of exampLe III (2g) in ethanoL (30 cc) is heated under reflux in the presence of methoxylamine hydrochLoride (5.8 cc of a 25% solution in water) for 2.

hours. The medium is diluted with water, extracted with dichloromethane and evaporated. The product is isolated by crystallization in a mixture of diisopropyL ether and heptane, in the form of a white powder, m.p. 1080 (mixture of the two geometric isomers).

Example X The compounds in which R11 H (4-hydroxyimino) m.p. 1950 18

H

i C IsooctyLphenoxy-polyoxyethylene-ethanoL 25 g 38 ti

R

11 (4-isopropoxyimino) oi 19 were prepared in the same manner.

Example X and those which follow iLLustrate the fungicidaL applications of the compounds according to the invention.

In these exampLes, the sprayin'gs of soLutions or suspensions of active substances are carried out under conditions such that the spraying of a solution or suspension of concentration equaL to 1 g/litre corresponds on average to the application of approximateLy 2 micrograms of active substance per cm of leaf area of the plant.

Under the conditions of Example X and those which follow, the compounds illustrated showed no phytotoxicity.

In these Examples, a product is regarded as providing complete protection against a fungal disease when the protection is at least 95%; the protection is regarded as good when it is at least 80% (but less than as fairly good when it is at Least 70% (but less than and as average when it is at Least 50% (but less than In the present specification, the percentages are except where otherwise indicated and except those relating to yields, percentages by weight. In the case where the percentages are expressed relative to the s.toichiometry, these are moLar percentages. As regards concentrations, some of these are expressed in ppm (part per million) which corresponds to mg/litre.

9 YC. 7-~ 39 Example XI In vivo test on Botrytis cinerea on tomato An aqueous emulsion of the active substance to be tested, having the following composition, is prepared by fine grinding: active substance under test: 60 mg Tween 80 (surfactant consisting of an oLeate of a polycondensate of ethyLene oxice with a sorbitan derivative) diluted to 10% strength in water: 0.3 cc the volume is made up to 60 cc with water.

i. This aqueous emulsion is then diluted with water to obtain the desired concentration.

to 40-day-old, greenhouse-cultivated tomatoes (variety Marmande) are treated by spcaying with diluted aqueous emulsions (called slurries) as defined above and at various concentrations of the compound to be tested.

I The trial is replicated twice with each concentration.

After 24 or 48 hours, the leaves are cut and placed in 2 Petri dishes (diameter 14 cm) the base of I 20 which has previously been provided with a disc of moist filter paper (5 leaflets per dish).

The inoculum is then applied by means of a syringe by depositing drops (3 drops per Leaflet) of a spore suspension. This suspension of 8otrytis cinerea spores was obtained from a 15-day-oLd culture, which was then suspended in a nutrient solution (100,000 units/cc).

Verification is carried out 3 and 6 days after tained and the acetone is then evaporated under vacuum. Under these conditions, at a dose of 1 g/litre, a good or total protection is observed with compounds la, Ib, la Ib, 3b, 5b, 6b, 8b, 9b, 12b, 14a, 14b, 14a 14b -and 17.

Example XII In viv test on Erysiphe 'graminis on barley (barLey mildew) BarLey, in pots, sown in plain soiL, is treated at the 10 cm height stage by spraying with an aqueous emulsion (caLLed sLurry) at the concentration indicated below. The triaL is replicated twice. After 24 hours, the barley plants are dusted with Erysiphe graminis spores, the dusting being carried out using diseased plants.

Under-these conditions, the following resuLts are observed: at a dose of 1 g/litre, good or total protection with la, lb, la Ib, 2a, 2b, 3a, 3b, 3a 3b, 4a, 4b, 6a, 6b, 7a 7b, 8a, 8b, 13, 14a 14b, 14a 14b, S17, 19.

Example XIII In vivo test on "Puccinia recondita" responsible for wheat rust Wheat, sown in plain soil in pots, is treated at the 10 cm height stage by spraying with diluted aqueous emulsions of the same composition as that described in Example VIII and at various concentrations of the compound to be tested. The trial is replicated twice at each concentration.

f 41 After 24 hours, an aqueous suspension of spores (50,000 sp/cc) is sprayed onto the wheat; this suspension was obtained from contaminated plants. The wheat is then placed for 48 hours in an incubation cell at approximately 180C and at 100% relative humidity.

After these 2 days, the relative humidity is Lowered to 60%. The condition of the plants is verified between the 11th and the 15th days, after inoculation, by comparison with the untreated control.

At a dose of 1 g/litre, good or total protection with compounds la, Ib, la Ib, 3a, 3b, 3a 3b, 5b, 6b, 7a, 7a 7b, 8b, 12b, 13, 14a, 14b, 14a 14b, 17 and 19.

Example XIV In vivo test on "Piricularia oryzae" 4 responsible for rice blast Rice, in pots, sown in a 50:50 mixture of enriched peat and pozzolana, is treated at the 10 cm height stage by spraying with an aqueous emulsion defined above at the concentration indicated below. The trial is repeated twice. After 48 hours, treatmient is carried out by applying on the leaves a suspension of spores obtained in pure culture.

Verification is carried out 8 days after inoculation. Under these conditions, the following results are observed: at a dose of 1 g/litre, good or total protection with compounds la, Ib, la 1b, 3a, 3b, 6a, 8a, 8b, 9a, 9b, 10b, 11a, 11b, 12a,,12b, 14a, 14b, 14a 14b and LX LI 3LLUU I centrated. The oiL obtained (40 g) consists of a mixture 42 ExampLe XV In vitro test on seed fungi and soil fungi The action of the compounds according to the invention is studied on the foLLowing fungi responsible for diseases of cereaLs and other pLants: 1) Pyrenophorae avenae 2) Septoria nodorum 3) HeLminthosporium teres 4) Fusarium roseum Fusari..n nivaLe 6) Fusarium cuLmorum 7) Rhizoctonia cereaLis r 8) Septoria tritici e t rtr9) Botrytis cinerea sensitive to carbendazime and to cycLic imides 10) Botrytis cinerea resistant to carbendazime and to cycLic imides 11) PseudocercosporeLLa herpotrichoides 12) Fusarium oxysporum F. sp. meLonis 13) Rhizoctonia soLani 14) HeLminthosporium gramineum The numbers which appear before the names wiLL be used to represent these fungi in Table (I) For each triaL, the procedure is as foLLows: a nutrient medium consisting of potato, gLucose and agar (PDA medium) is introduced supercooLed into a series of Petri dishes (20 cc per dish) after sterilizing in an autocLave at 1200C.

i LUL i 43 In the course of filling the dishes, an acetone solution of the active substance is injected into th'e supercooled medium, to obtain the desired final concentration.

Petri dishes similar to the above, into which are poured similar quantities of a nutrient 'medium which does not contain the active substance, are taken as control.

After 24 or 48 h each dish is seeded by depositing a fragment of mycelium originating from a previous culture of the same fungus.

The dishes are stored for 2 to 10 days (depending on the fungus being tested) at 220C, and the growth of the fungus in the dishes containing the active substance to be tested is compared with that of the_same fungus in the dish used as the control.

For each compound tested, the degree of inhibition of the fungus considered, at a dose of 30 ppm, is thus determined. The results are given in the following tabLe.

i *i 44 Compound Fungi KI

I

.4 it o 0 0006 ft ft ft ~ft 1t~5 25 lb I o l0 I10 100 I 95 lo 10 lI10 9 b 11001 90 1100 11 1100001 l o la 2-b! 100 I 95 I100 I 95 I100 lo 10 go9 2 a 15095180! 501 8011001801 2b I 80 I110 I 80 I 50 I 090 0go .3a I 95 I 90 I100 I 50 I 80 I 80 3b, 95 I 95 I100 I 80 I 90 lo 10 go9 3a 3bI 80 1 0 1 80 1 0 1 80 1 80 1 4 a I 90 I 0 I 90 I 80 I 80 I 90 41 1 951801951801 8011001901 5a I 50 I 90 I 50 I 50 I 50 I 50 Sb 100O 100I100 901 9511001951 6 a 50 I 90 I 50 I 50 I 50 I 50 6 b I1001 95 I 95 I 80 I 90 I 90 7 a I .95 I 95 I 95 I 0 I 0 I 0 I 7 b 9 95 90 I 95 I 0 I 0 I 0 7a 7bl 50 1 95 1 50 1 0 1 0 1 0 1 8 a I 95 I 80 I 95 I 80 I 50 I100 8b I100 I 90 I 95 I 80 I 80 I 90 9 a I 95 I 90 I 95 I 80 I 80 I 90 9h b 80 I 95 I 95 I 0 I 0 so0 10a 1801 01801501901 951801 I 90 I. 80 I 90 I 0 I 0 I 50 I 80 I 11a 190150195 01 0 01801 2-lb I 90 I 80 I 95 I 0 I 0 I 0 I 12a I 90 I 80 I 95 I 0 I 80 I 80 I 80 1 12b I 95 I 90 I 95 I 80 I 80 I 90 Cornpoundl Fungi No- 1 12 3~ 41516171 14a I 95 I 95 I100 I 95 I100 lo 10 go9 14b I 95 I 90 I100 I 90 I 95 I100 go9 I 14a+14b1 100 95 I100 I100 I100 100o I 0 I 95 I 80 I 0 I 0 I 50 I 0 16 I80f 01801 01 050101 17 I 80 I 0 I 80 I 80 I 95 I 80 19 I 90 I 0 I 80 I 80 I 90 I 50 I9101 901 951901901 46 Compound Fungi o 1 8 9 10122 12 13 14 la 1100 I100 I100 I100 I100 80 I1001 lb I l-a lbI 100 2a o 2b o 3a I 95 3b I100 3a +3bI 01 4a I 0 4b I 0 I 0 5b I 0 6a I 0 6b I 50 7a o 7b I 0 7a 7bl I 8a o 8b o 9a o 9b o 2Z5 10a I 50 o 12-a I 0 2-lb I 0 12a I 0 12b I 0 13a 95 95 95 80 90 95 80 95 95 0j 95 50 95I 95I 90 95I 80 95I 90 95I 80 90 0I 80 50I 95I 0I 95 100 100 95 1,00oo 100 95 I100 50 I100 90 I 95 100 I 95 95 I 0 95 0 95 I 90 0 lo10 90 I100 50 I100 95 I100 95 I 95 I 95 I 90 I 95 I100 80 I 80 95 I 90 90 go0 90 I100 01 0 95 I 80 80 I 50 80 I 80 80 I 80 95 I 90 0 I100 0j 80 01 80 01 0I 95I 0I 95 0I 80 0I 0I 50 80 80 80 80 0I 50 50 80 01 80 50 80 I1001 90 I951 0 I801 0 I801 0 I901 80 I951 0 I801 0 I901 0 I951 0 501o 90 I90 1 0 I 501 80 I 95I1 80 I80 1 50 80 80 I951 80 I951 80 I951 80 0 1 0! 50 1 901 50 I951 80 I951 80 80 I1001 01

I

I -4? Compound Fungi No. 18 19 10 11i 12 132 141 14a I 100 I100 I100 1 100 1 80 1 1001 14b I 0 I 95 I 95 100 I 80 I 80 1 1001 14a+14b1 50 1 95 1 95 1100 1 100 1 80 1 951 0 1I 0f O 95! Of 0 f Of 0 16 0 Of Of Of Of 01801 17 0 080 801 Of f0 0 1801 18 1 1 1 1 19 I01 of 0 0 Of 0 901 0 0801 90100 f 50f1 80 1 901 -48

OR

2 R EP 151084 ii0 1 II A ~Tr or Im

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1 0 X2 A3 Tr or Im

IR

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49 0

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4 4 t 11ff It ii 4 It 4 Tr or Im 0 R1 xl Hal RgR Tr R 3 or Im 11 Hal II Tr R4 or Im

L

50 0 R 2

R

1 Aq1 xl R 5 QR6 Ila

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R II lb

R

Im 4 o~ 0 1 a lao a I A OH X\1 jR

IIIC

A

R Ille Tr or Im Tr or Irn I lId IVa Z R 4 R3 R.R 3 or Im 51 A QR 6 QR 6 Tr orI Irn R 3 0 0 00 006 .0 *0 0 V0 R 00 N-R 7 T r or Im A 0R1 xl

R

5 R R VI Tr

R

4 3 or Im N-R 1 0 Vlla R5 VIa R 4 A xl NR 8

R

Z R 4R3 viii

Claims (16)

1. 2. A compound according to claim 1 wherein m is 0.
2. 3. A compound according to claim 1 or 2 wherein Y represents a halogen atom and n is 1, 2 or 3. I I ~r~ 55
3. 4. A compound according to claim 1, 2 cr 3 wherein n is 1 or 2 and Y is a halogen atom in the ortho and/or para positions. A compound according to any one of the preceding claims wherein n is 2 and Y is halogen in the ortho and para positions.
4. 6. A compound according to any one of the preceding claims and which conforms to the formula: Se R 2 Hal R 3 or Im wherein R 1 R 2 R 3 R 4 and R which may be the same or different, each represent a hydrogen atom or a lower
5. 7. A compound according to any one of the preceding claims wherein R i R 2 R 3 R 4 and R 5 each represent hydrogen and halogen atoms within the definitions of Hal and X are the bromine or the chlorine atom. ^I i -56-
6. 8. A compound according to any one of claims 1 to and which conforms to the formula: R6 R 4 wherein R 1 R 2 R R 4 and R~ which may be the same or different, each represents a hydrogen atom or a lower alkyl or cycloalkyl group, X 1 represents a hydrogen atom or a lower alkyl or cycloalkyl group, and R 6 represents a hydrogen atom or an optionally substituted lower alkyl or cycloalkyl group.
7. 9. A compound according to claim 8, whereinR1 R 2 R, R 4 and R.each represent a hydrogen atom, X 1 represents a hydrogen atom or a lower cycloalkyl or alkyl group and R 6 represents an optionally substituted lower cycloalkyl or alkyl group.
8. 10. A compound according to claim 8 or 9 wherein QI represents 0. A- -oayeeo h !ucUnn~~~ LI-I-U
9. 11. A compound according to any one of the preceding claims wherein Y is chlorine and halogen atoms represented by Hal, X 1 or X 2 are chlorine or bromine.
10. 12. A compound according to claim 1 hereinbefore identified as any one of compounds la, lb, Ic, Id, 2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a, 6b, 7a, 7b, 8a, 8b, 9a, 9b, 10a, 10b, lla, llb, 12a, 12b, 13, 14a, 14b, 15, 16, 17, 18, 19 and 0 o o 0 0 0 0 0 0 0~4
11. 13. A process for the preparation of a compound of formula I depicted in claim 1, wherein X 2 represents a halogen atom and the other symbols are as defined in claim 1, which process comprises: reacting a haloketone of the formula: i r r S° 15 0 0 0 001 o oI t* 0 A I LIIIIIWIlI~~ 58 0 A IIa R wherein A and R s are as defined in claim 1 and Z represents a halogen atom, with an organometallic compound of the formula: o a o, M R 5 IIb R 3 R 2 2 wherein M represents an alkali metal or a group MgHal or ZnHal in which Hal represents a halogen atom, and the other symbols are as defined in claim 1, to obtain a compound of the formula: OH X SR 4 M J I I ~i 59 wherein Z is as hereinbefore defined and the other symbols are as defined in claim 1; reacting the compound of formula IIc with an unsubstituted triazole or imidazole, in the presence of an organic or inorganic base, and in a solvent, to obtain a compound of the formula: 00 0 0 D 0 0 a e o 1 Q o o o lid R R Tr or R3 4 Im 1i wherein the various symbols are as defined in claim 1; reacting the compound of formula IId with a halogen or a mixed halogen in an inert solvent to obtain a compound of the formula: IIe II I urrrcs~ S- wherein Hal represents halogen and the other symbols are as defined in claim 1; cyclization of the compound of formula IIe in the presence of an organic or inorganic base to obtain the compound of formula II. th. A modification of the process according to 13 claimA=4 in which the compound of formula IIc is reacted with a halogen or mixed halogen in an inert solvent to obtain a compound of the formula: R 2 A 1 Hal xi R 3 R wherein Hal and Z are as defined in claim 4 AT and the other symbols are as defined in claim 1, cyclizing the compound of formula IIf in the presence of an organic or inorganic base to obtain a compound of the formula: 61 R 2 0J R SIIg Hal R SR 3 R 4 13 wherein Hal and Z are as defined in claim414 and the other symbols are as defined in claim 1, and reacting the compound of formula IIg with an unsubstituted imidazole or triazole in the presence of an organic or S inorganic base in a solvent to obtain the compound of formula II. y 1 A process for the preparation of a compound of the formula I depicted in claim 1 wherein X 2 represents QR and the other symbols are as defined in claim 1 which comprises the reaction of a compound of formula II depicted in claim 6 or formula IIg depicted in claim4qS with a heteroatomic nucleophile of the formula R 6 -Q-E in which R6 and Q are as defined in claim 1 and E is a cation, in the presence of a base and, optionally, a phase transfer catalyst and, when a compound of formula IIg is used as starting material, reaction of the compound obtained with an unsubstituted triazole or imidazole. A process for the preparation of a compound of formula I depicted in claim I wherein X 2 represents QR6 in which R 6 is an optionally mono- or polyhalogenated 62 lower alkyl group and Q is as defined in claim 1 which comprises the reaction of a compound of formula III depicted in claim 8 wherein R 6 represents a hydrogen atom or of the formula: R 2 R 0 1 A xl R 5 QR6 Z R3 Z R3 4 3 IIIa 44 wherein R 6 represents the hydrogen Z is as defined 13 in claimi 4 and the other symbols a.r ags defined in claim 1 with an alkyl halide containing one or more halogen atoms, in the presence of an organic or inorganic base and, when a compound of formula liIa is used as starting material, by reaction of tLe compound obtained with an unsubstituted triazole or imidazole. -17. A process for the preparation of a compound of formula I depicted in claim 1: wherein X 2 represents a hydroxy group which comprises the reaction of a compound of formula II depicted in claim 6 or II-g depicted in claim4AP with a iJ~ p t- d I 1 ~tc~~c~ L m c i, 1-i 63 metal hydroperoxide, hydroxide, oxide or superoxide or the reaction of a compound of formula II or IIg with an alkali metal or alkaline earth metal carboxylate in the presence of a phase transfer catalyst; (II) wherein X 2 represents N which comprises the reaction of a compound of formula II or IIg with an alkali metal or ammonium azide; (III) wherein X 2 represents an alkoxythioyl, o, 10 aryloxythioyl or aralkyloxythioyl group which comprises 0 0 the reaction of a compound of formula II or IIg with an ,t alkali metal or ammonium xanthate; (IV) wherein X represents NR R, wherein R and R 9 are as defined in claim 1 which comprises the reaction of a compound of formula II or IIg with an a amine of the formula H-NRR and when a compound of formula IIg is used, reaction of the compound obtained with an unsubstituted triazole or imidazole. A process for the preparation of a compound of Sformula I wherein X 2 represents a hydroxy group which comprises the reaction of a compound of formula IIc or 13 IId depicted in claim 1 4 with a peroxide to obtain, respectively, an epoxide of the formula: r o k .3 0' 1 i i- Ti' I 1 64 A OH X IlIb ii 4' gIrt it 1 4 '44 ii I S IlIc Tr or Im 13 wherein Z is as defined in claim 4 1- and the other symbols are as defined in claim 1, hydrating the epoxides to obtain, respectively, triols of formula IIId or IIle, cyclising the triols of formula: R 5 OH z 3 4 IIId 'S or OH X 1 R A OH 1 I e 5R o e2 5 OH 0 3 r\ R 3 R 4 or Im respectively, the compounds of formula IIIa depicted in 000 0 whrclaimn Z ois aII depicted in claim 8, and reacting the in the A process for the preatiarting of a compound of formula I depicted in claim 1 wherein Xlana d epicted in represent -0 which comprises the oxidation of a compound of formula III or IIIa depicted in claim 8, and reacting wherein un is as defined in claim44, QR a represents a hydroxy group, X proesens fora hydrogen atom, and the other symbols are as defined in claim 1 and when a compound represent -O which comprises the oxidation of a compound r.v t m of formula III or lIla depicted in claim 8 or4= wherein symbols are as defined in claim 1, and when a compound of formula IIIa is used as a starting material, reaction of the compound obtained with an unsubstituted triazole ffruaIIo4li eitdi lim8o^? hr (I- 1 1 Z sa eie ncanIlQgrpeet yrx 66 or imidazole. zt.. A process for the preparation of a compound of formula I depicted in claim 1 wherein X and X together represent which comprises the thionation of a compound of formula: 'R Tr R 3 or Im IVa Z R 4 R wherein X i and X 2 together represent Z is as defined 13 in claim 4 l and the other symbols are as defined in claim 1 and, when a compound of formula IVa is used as a i ;3 r~~ r. 9, t~, r ir i i 1 67 starting material, reaction of the compound obtained with an unsubstituted triazole or imidazole. A process for the preparation of a compound of formula I depicted in claim 1 wherein X and X simultaneously represent QR 6 or together represent a group of formula -Q-R wherein Q, R and R are as defined in claim 1, which comprises the reaction of a compound of formula HQR 5 or HQ-R -QH with a compound of formula IV or IVa depicted in claim/Ml wherein X and X 2 together represent =0 or in the presence of an acid catalyst and in a solvent, and when a compound of S' formula IVa is used as a starting material, reaction of the compound obtained with an unsubstituted triazole or ;imidazole. 2a- A process for the preparation of a compound according to claim 1 wherein X and X each represent a halogen atom which comprises the reaction of a compound of formula IV or Iva depicted in claim 4 2 wherein X and X 2 together represent =0 with a phosphorus pentahalide optionally in the presence of an inert aprotic solvent and optionally in the presence of quaternary ammonium halide. A process for the preparation of a compound of formula I wherein X i and X 2 together represent -N-Ri 0 wherein Ri is as defined in claim 1 which comprises the reaction of a compound of formula IV or IVa depicted in S o claim 4 2 with an amine of formula R 1 -NH 2 or a salt I r 1 L7, 1I-L L-1LliY c U 68 thereof and, when a compound of formula IVa is used as starting material reacting the compound thus obtained with an unsubstituted imidazole or triazole. A process for the preparation of a compound of formula I wherein X. and X 2 together represent -N-R 0 in which R 10 represents a group OR 11 wherein R 1 1 represents an optionally substituted aralkyl or lower alkyl radical which comprises the reaction of a compound of formula I wherein X. and X 2 together represent a group =N-OH with an alkylating agent of formula R D in which R is an optionally substituted aralkyl or lower alkyl radical and D represents, as leaving group, a halogen, sulphonium, ammonium, sulphonate or sulphate group, in the presence of an organic or inorganic base.
12. 24.1S. A process according to any one of claims 13 to -24 substantially as hereinbefore described. 2M-2 A compound of general formula I wherein the various symbols are as defined in claim 1 when prepared by a process claimed in any one of claims 13 to425. 2g A fungicidal composition which comprises, as active ingredient, a compound according to any one of claims 1 to4l=3 or an agriculturally acceptable salt thereof or an agriculturally acceptable addition complex thereof with a metal salt in association with an agriculturally acceptable carrier. jML&. A composition according to claim4d2 which Scomprises from 0.5 to 95% by weight of active 'NT C 69 ingredient.
13. 29. A composition according to claim 27 substantially as hereinbefore described. A method for the control of fungal diseases at a locus which comprises the application of an effective amount of compound according to any one of claims 1 to 12 or a salt thereof or an addition complex thereof with a metal salt. 0
14. 31. A method according to claim 30 for the control of 0e 10 fungal diseases of plants at a locus. S, 32. A method according to claim 31 which comprises the o ,application of the active ingredient at a rate of 0.005 0 •t to 5 kg/ha.
15. 33. A method according to claim 30 which comprises the 0 15 application of the active ingredient at an application rate of 0.01 to 0.5 kg/ha.
16. 34. A method according to claim 30 substantially as hereinbefore described. Dated this 2nd day of August, 1989. RHONE-POULENC AGROCHIMIE, By its Patent Attorneys, DAVIES COLLISON AI L< i