NZ230531A - Triazole- and imidazole-containing compounds useful for preparing triazolyl- and imidazolylmethyl substituted tetrahydrofuran derivatives; preparation of such compounds - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £30531 250 NO DRAWINGS Ur.djr ih," provisions o« Regu-Iclton 23 (1) the ..CGrtJ£fcl«.....

Priority D*te(s): • •Vrt • •S r» •r<•*•«««•««»«»•»•»»*»•»•• Complete Specification Fi!ed;<££.Cv5£? ci.~ CoIlt2fc£r2*./ t>o>. .b 1.. *27 MOV *090 Publication Date: P.O. Journal. No: .. ISBlfe.; Specification hss been anto^Med to 19 NEW ZEALAND PATENTS ACT. 1953 No.: Date: COMPLETE SPECIFICATION NOVEL TRXAXOLB AMD I MX DAI OLE DERIVATIVES amd wocehm 101 irspmzn thz smib I/We, RBONB-POOLEMC JXawcniHIB, • French Body Corporate of 14-20 Rue Pierre Balxet, Lyon 9e, Prance, hereby declare the invention for which I / we pray that a patent may be granted to me/us, and the method by which it is to be performed, to be particularly described in and by the following statement: - (followed by page lA) - 1A - ^30531 The present invention relates to new compounds and to processes for their preparation. More particularly, the invention relates to compounds which ace inter alia useful as internediates in the preparation of fungicides.

Nunierous compounds, especially fungicides, containing triazole groups are already known , in particular, from New Zealand Patent Specification Wo, 210932 which describes compounds of the formula shown at the end of the description and their use as fungicides. The compounds of the present invention are novel and are not described in New Zealand Patent Specification No. 210932.

There is a continuing need for new compounds which have improved properties in the treatment of fungal diseases or which have an improved spectrum of activity, it has been found that certain new compounds represent, in some aspects of their activities, such an improvenent.

In this regard, the reader's attention is directed to New Zealand Patent Specification No. 220050 which describes and claims compounds of formula (I) depicted hereinafter, wherein: A represents a group (Y)a Ph-CCH,)^- in which Ph is a phenyl ring and o is 0 or 1, preferably 0, Y is a halogen atom or a cyano or nitro group, or an optionaly halogenated alkyl or alkoxy group, n is a positive integer 1, 2, i cr 5* c.r zero, tiv? 230531 groups Y being identical or different when n is greater than 1, Tr represents a 1,2,4-triazol-l-yl group and In a 1,3-imidazol-l-yL group, Ri' R2» Ri * R« dn<3 *» • wh*ch nay be identical or different* represent a hydrogen atom or a lower alkyl, lower cycloalkyl, a:yl (preferably phenyl), aralkyl (preferably benzyl), lower alkoxy, lower alkanoyl or aroyl (preferably benzoyl) radical, these radicals being optionally substituted (for example, with one or nore atoms or radicals such as halogen atons and lower, alkoxy radicals), Xj and Xj , which nay be identical or different, each represent a hydrogen aton; a halogen aton; a lower alkyl, lower cycloalkyl, aryl (preferably phenyl) or aralkyl (preferably benzyl) radical, these radicals being optionally substituted as hereinbefore defined for Rx to Rs; a O-Rj group in which Q represents 0 or S, and Rc represents the hydrogen aton or a lower alkyl, lower cycloalkyl, aryl (preferably phenyl), aralkyl (preferably benzyl), acyl, aroyl or thioacyl (preferably acetyl, thioacetyl, propionyl, thiopropionyl or benzoyl); alkoxythioyl, aryloxythioyl or aralkyloxythlcyl (the tern thioyl corresponds to C = S(S)] radical; these radicals being optionally substituted as hereinbefore defined for Rt to Rs and 230531 being identical or different when Xt and X, each represent OR4 cr SRs ; an -NR#R# group in which R# and R# , which nay be identical or different, represent the hydrogen aton or a lower alkyl, lower cycloalkyl, aryl (preferably phenyl) or aralkyl (preferably benzyl) radical, these radicals being optionally substituted as hereinbefore defined for Rt to Rs, or Ra and R} nay together form a divalent hydrocarbon radical, containing from 2 to 6 carbon atons, one of the carbon atons being optionally replaced by an oxygen, sulphuror nitrogen atom, the divalent hydrocarbon radical itseif being optionally substituted (for exanple with one or nore halogen atoas or optionally halogenated lower alkyl or lower alkoxy radicals or a hydroxy radical); an N, group, provided that and X, do not both represent N,; or X^ and X^ together represent a group of foraula -Q-R7-Q- wherein Q is as hereinbefore defined and in which R, is a divalent hydrocarbon radical, containing from 2 to 6 carbor. atoas, one of the carbon atoas which is not attached directly to 0 being optionally replaced by an oxygen or nitrogen atoa, the divalent hydrocarbon radical being optionally substituted (for example, with one or aore halogen atoms or lower alkyl, lower alkoxy or hydroxy radicals); or X1 and together represent an =N-R^q group in which R1Q represents a lower alkyl, lower cycloalkyl, aryl (preferably phenyl) or aralkyl (preferably benzyl) radical, or a group of formula ORxl in which Rt x is a lower alkyl, aralkyl or aryl radical, these radicals being optionally substituted as hereinbefore defined for R^ to Rs, or Rl0 represents hydroxy; or X1 and X3 together represent ■ 0 or ■ S; and with the proviso that if is chosen from the group consisting of hydrogen, a lover alkyl radical, a lower cycloalkyl radical, an aryl radical or an aralkyl radical, X2 does not represent an itoa or radical chosen fron that group; salts thereof and addition complexes thereof with aetal salts.

The salts according to the invention of ns 220050 are preferably acceptable in agriculture and include the hydrochloride, sulphate, oxalate, nitrate or arylsulphonate; the addition coaplexes of the coapounds of the invention with aetal salts are preferably with iron, chroniua, copper, aanganese, zinc# cobalt, tin, aagnesiun and aluainiua salts. The coaplexes cay be prepared by known aethods; for exaaple, sine coaplexes aay be obtained by reacting a coapound of foraula I with sine chloride.

In this specification it is to be understood that the adjective lower, when it qualifies an organic radical, aeans that the radical contains no aore than six carbon atoas. Alkyl and alkoxy 230 5 31 radicals or moieties in this specification may be straight or branched-chain.

The compounds of formula I ana cocpouics jucrc:ng to the present invention which nay, if desired, be used- as intermediates in trie - processes for their preparation, and which are described hereinafter, may exist in one or more isoneric forms depending on the number of asymmetric centres in the molecule. The invention relates to all the optical isomers as well as to their mixtures, in particular racemic mixtures, and to the corresponding diastereoisomers. The separation of the diastereoisoaers and/or the optical isomers may be earried out according to methods known per se.

Preferred fungicidal compounds of the invention of NI 220050 ^ IS are those of formula I in which Y is a halogen atoa and n is 1, 2 or 3.

Compounds of formula Z in which n it 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.

Preferred coopounds of the invention of HI 220050 include those of formula I wherein X2 represents a halogen atoa, such compounds being depicted in formula IX in which Bal 25 represents a halogen atom, and those of foraula X wherein X, represents a group -QR4, such compounds being depicted in formula III.

The triazole compounds of formula II in which Rt , Rj, Rj, R,, and S5, which may be the same or different, each represent a hydrogen atom or a lower cycloalkyl or alkyl group, Kal represents a halogen aton, preferably chlorine or bromine and X4 represents a halogen, preferably chlorine or bromine, or hydrogen atomfand advantageously a hydrogen atom, are especially preferred fungicidal coopounds of the invention.

The triazole compounds of formula III in which Rx, Rj » Rj» R4 and Rs represent a hydrogen aton or a lower cycloalkyl or alkyl group, Y, n and a are as hereinbefore defined, Xt represents a hydrogen atoa or an optionally substituted lower cycloalkyl or alkyl group, R( represents a hydrogen aton or an optionally substituted lower cycloalkyl or alkyl group and the other symbols are as hereinbefore defined, are also preferred fungicidal conpounds of the invention.

Preferred triazole compounds of foraula II are those in which Rt, , Ra , R4 and R, represent a hydrogen atoa and the halogen aton(s) within the definitions of Kal, Xa and Xa are the bromine or the chlorine atoa.

Preferred triasole conpounds of foraula III are those wherein Rj , R. , Rj, R^ and R} represent a hydrogen aton, Xt represent a hydroger. atoa or lower cycloalkyl cr alkyl, Rj represents an optionally substituted lower cycloalkyl or alkyl group end preferably Q represents C.

According to a further feature of the invention of NX 220050 conpounds of foreula I wherein X2 represents a halogen 230531 atom (ie. compounds of foraula II), are prepared by a process which comprises: (a) reacting a haloketone of formula Ila (which nay be obtained by a known process) wherein A and Rs are as hereinbefore defined and 2 represents a halogen atoa, with an organometallic compound of formula lib, wherein K represents an alkali metal or a magnesium-containing group (NgHal) or a zinc-containing group (ZnHal) in which Hal represents a halogen atom, to obtain a compound of formula lie wherein the various symbols are as hereinbefore defined; (b) reacting the compound of formula lie with an unsubstituted triazole or imidazole in the presence of an organic or inorganic base, for example pyridine, triethylamine, sodium hydroxide, potassium hydroxide, carbonates and bicarbonates of alkali or alkaline earth netals, and in a solvent such as, for example, an alcohol, ketone, amide, nitrile or optionally halogenated aromatic hydrocarbon to obtain a compound of formula lid wherein the various symbols are as hereinbefore defined; (c) reacting the compound of formula lid 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 foraula lie, wherein the various symbols are as hereinbefore defined; (d) cyclisation of the compound of formula lie in 250531 the presence of an organic or inorganic base preferably at arsbient temperature to obtain the compound of foraula II.

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

Step (b) is preferably carried out at a temperature of from 80*C to the reflux temperature of the reaction mixture and in a molar ratio of IIc:imidazole or triasole which is preferably from 1.1 to 0.2, to obtain the compound of formula I Id. The reaction generally passes through an epoxide intermediate of formula Ilh which may, if desired, be isolated or prepared separately by known methods.

In step (d) the organic or inorganic base is, for example, a base listed in step b in a molar ratio of compound Il: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 aside such as dioethylforoaaide).

A modification of the process described above for 230531 c the preparation of the compounds of formula I wherein X2 represents a halogen comprises carrying out stage (b) after stage (d), using the same reaction conditions for the different stages. Thus, the compound of formula lie 5 is reacted wich a halogen or halogen halide (mixed halogen) in an inert solvent to obtain a compound of formula Ilf, the compound of formula ZIf is then cyclized in the presence of an organic or inorganic base to obtain the compound of formula llg, and the compound of formula 10 IZg is then reacted with an unsubstituted triazole or imidazole group to obtain the compound of formula II.

According tu * further feature of the invention of NZ 2200SO compounds of formula I wherein X2 represents QRC , and is other than Hal (compounds of formula III)* are prepared 3-5 by the reaction of a compound of formula II or Xlg with a*' heteroatomic nucleophile of formula R4-Q-E, in which R4 and 0 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, 20 a phase transfer catalyst and, when a compound of formula llg is used as starting material, reaction of the compound of formula Ilia obtained with an unsubstituted triazole or imidazole. The reaction is generally carried out in a suitable solvent and at reaction temperatures which are 25 generally from -30*C to the reflux temperature of the reaction mixture and in a molar ratio III:R(QE which is preferably froa 1.2 to 0.1. -10 2305 31 According to a further feature of the invention of NZ 220050 compounds of formula III wherein R( is an optionally ecr.o-or i' >lyhalogenated lower alkyl group, are prepared by reacting a compound of foraula III or Ilia wherein Rc represents a hydrogen atom with an alkyl halide containing one or nore halogen atoms in the presence of an organic or inorganic base and, when a compound of foraula Ilia is used as starting material, by reaction of the compound obtained with an unsubstituted triasole 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 of NZ 220050 compounds of formula I wherein X} represents a hydroxy group (i.e. compounds of formula IZI in which 0 represents the oxygen atom and R( the hydrogen atoa), are prepared by * the reaction of a compound of foraula XX or XXg with a aetal (preferably an alkali aetal or alkaline earth aetal) hydroperoxide, hydroxide, oxide or superoxide. The reaction with the aetal coapound is generally carried out in the presence of an inert organic solvent, at a temperature froa -30* to the reflux temperature of the reaction nlxture, in a aolar ratio which is preferably froa 1.1 to 0.2.

According to a feature of the invention of KS 220050 compounds of-formula I wherein X, represents Nj, are prepared by the reaction of a coapound of foraula XX or llg with an alkali aetal or aaaoniua aside, preferably in a aolar ratio of 23 0 5 31 from 1.1 to 0.2, preferably in an aprotic solvent, at a temperature of froa -30° to the reflux teaperature of the reaction mixture and, when a compound of formula llg is used, reaction of the compound thus obtained with an unsubstituted imidazole or triasole. when X} in formula I represents an alkoxythioyl, aryloxythioyl or aralkyloxythioyl group, the compounds of formula llg or II are reacted with an alkali metal or ammonium xanthate and, when a compound of formula llg is used, the compound thus obtained is reacted with an unsubstituted triazole or imidazole.

According to a further feature of the invention of NZ 220050 compounds of formula I wherein X, represents a hydroxy group, are prepared by the reaction of a compound of formula lie or lid with a peroxide to obtain, respectively, an epoxide of formula Illb or IIIc, hydrating the epoxides to obtain, respectively, the triols of formula IXId or Xlle, cyclising the triols in the presence of a dehydrating agent such as hydrochloric, hydrobromic, sulphuric or sulphonic acids, to obtain, respectively, the conpounds of formula Ilia or IIX and reacting the coapound of formula Ilia 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 aay be protected in a manner known per se for compounds of formula Illd and Ille. 2305 31 Compounds of formula I wherein X2 represents a hydroxy group may be prepared by the reaction of a compound of foraula XI or llg with an alkali metal or alkaline earth metal carboxylate, especially sodium 5 bensoate, in the presence of a phase transfer catalyst and optionally in the presence of an aprotic polar inert solvent, if required in the presence of water, and at temperatures of from 0° to the reflux temperature of the reaction mixture and, when a compound of formula Xlg is 10 used, reaction of the compound thus obtained with an unsubstituted triasole or imidasole.

Compounds of formula X wherein and X, together represent -0 (conpounds of formula XV wherein Xx represents the oxygen atom), are prepared by the oxidation 15 of a compound of formula XXXa or XIX in which QRf represents hydroxy and Xt represents hydrogen, to obtain a compound of foraula XV or XVa and, when a compound of foraula Ilia is used as starting naterial, reaction of the coapound obtained with an unsubstituted triasole or 20 imidazole. The gen-halogenated coapounds (Xt-X2"Hal) of foraula I are prepared by reacting a phosphorus pentahalide with a corresponding ketone (a coapound of foraula IV or IVa in which Xt represents an oxygen atoa), optionally in the presence of an inert aprotic solvent and 25 optionally in the presence of a quaternary anaoniua halide, preferably at aabient temperature, and when the starting aaterial is a coapound of foraula IVa, reaction of the coapound obtained with an unsubstituted triazole or imidazole.

The conpounds of fornula I wherein Xt and X2 together represent -S (conpounds of fornula IV wherein X, represents the sulphur aton) are prepared by the thionation of a coapound of formula IV or IVa wherein X: and Xj together represent -0, for example, with H2S or P2S3 in a nolar ratio which is preferably from 1.1 to 0.2, in the presence of an inert organic solvent (pyridine or hydrocarbon, for example) at a tenperature of from 20° to the reflux tenperature and, when the starting naterial is a conpound of foraula IVa, reaction of the compound obtained with an unsubstituted triazole or imidazole.

The conpounds of foraula I wherein Xa and X, siaultaneously represent QR4 (ie. a coapound of foraula V) are prepared by the reaction of a coapound of fornula IV or IVa in which xt and X2 together represent -0 or -S with a coapound of foraula HQR^ wherein 0 is 0 or S in a aolar ratio which is preferably froa 1.1 to 0.2, in the presence of an acid catalyst and in a suitable solvent, which nay be the alcohol or thiol itself, or an inert solvent such as hydrocarbons or alcohols and, when the starting aaterial is a coapound of foraula IVa, reaction of the coapound obtained with an unsubstituted triazole or inidazole.

Conpounds of fornula I wherein Xx and X2 together represent -Q-R,-Q- and R? is as hereinbefore defined may 230531 be prepared by the process described for the preparation of coopounds of foraula I wherein Xt and X2 simultaneously represent QR4 by using a compound HQ-R7-QH instead of HQR, .

Compounds of formula I wherein represents NR(R,, are prepared by reacting a compound of formula II or llg with an amine of formula H-NR,Rf, generally in a molar ratio from 1.1 to 0.2, optionally in the presence of another organic or inorganic base to obtain a compound of formula VI fron the compound of formula II and a compound of formula Via from the compound of formula llg and, when ♦ a compound of formula llg is used as starting material, reacting the compound obtained with an unsubstituted triasole or imidazole.

Compounds of formula I wherein X, and X, together represent - N-Rl0 (ie. a compound of foraula VII), are prepared by reacting a compound of formula IV or IVa with an amine of formula Rt0-NB> 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 coapound of formula IVa is used as starting material, reacting the coapound (of formula Vila) thus obtained with an unsubstituted imidazole or triasole.

Compounds of formula I wherein Xj and Xa together represent -N-Rt0 in which Rl0 represents a group ORlt wherein Rtl represents an optionally substituted aralkyl or lower alkyl radical are prepared by the reaction of a 230531 compound of formula VII in which Rl0 represents a hydroxy radical with an alkylating agent of formula Ht,D in which Rx x 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 inventiuu of NZ 220050 also relates to compounds which can be used as intermediates in the preparative processes described above: the compounds of formula IX, lie, lid, Ilf, llg, Ilh, III, Ilia, Illb. IIIc, Hid, Hie, IV, IVa, V, va. vb, VI, via, VII and Vila in which R; to R# , Y, Tr, Im, m, n, xx, X2, 0, Hal and Z are as hereinbefore defined are novel and as such constitute features of the invention.

The present invention also provides coopounds which are suitable for use as intemediates in the preparation of the coopounds of fornula I. More particularly, the present invention can be said to consist in a coopound which is a trizaole or imidazole derivative of formula lie: in which A is (Y) Ph- (CH,)- wherein Ph is a phenyl nucleus, m is 0 or n * m 1 and n is 0 or an integer less than 6; each Y# which may be identical or different to each other.Y if n is greater than 1, is a halogen atoa, a cyano or nitro group or an unhalogenated or halogenated alkyl or alkoxy group; *5 R3 R4 Kal 2 He - 15A - 230531 Tr is a 1,2,4-triazol-l-yl group and In is a 1,3-imidazol-l-yl group R1 to R5' may ^e identical or different, are each a hydrogen atom or an unsubstituted or substituted alkyl, C3-c6 cycloalkyl, aryl, aralkyl, C^-Cg alkoxy, Cj-Cg alkanoyl or aroyl group; Xj is a hydrogen or halogen atorr.; an unsubstituted or substituted Cj-Cg alkyl, C3-Cfi cycloalkyl, aryl or aralkyl group; a -Q-Rg group wherein Q is 0 or S and Rg is a hydrogen atoa or an unsubstituted or substituted Cj-Cg alkyl, Cj-Cg cycloalkyl, aryl, aralkyl, acyl, thioacyl, alkyloxythioyl, aryloxythioyl or aralkyloxythioyl group or a -NRgRg group wherein R0 and Rg, which aay be identical or different, are each a hydrogen atom or an unsubstituted or substituted Cj-Cg alkyl, Cj-Cg cycloalkyl, aryl or aralkyl group or Rfl and R^ aay together Cora a single divalent hydrocarbon group containing froa 3 to 6 carbon atoas, it being possible for one of the carbon atoas in the hydrocarbon group to be replaced by an oxygen, sulphur or nitrogen atoa, it also being possible for the hydrocarbon group to be substituted; and Hal 1 and Hal 2, which aay be identical or different, art. each a halogen atoa; or an agriculturally acceotable salt thereof or coaplex thereof with a aetal salt.

Preferably, n is 0 and the coapound which is a triasole derivative. 23 0 5 3 1 - 15B - In a further preferred embodiment, at least one of to R$, which may be identical or different, is a C^-Cg alkyl, Cj-Cg cycloalkyl, aryl, aralkyl, Cj-C6 alkoxy, Ci-Cg alkanoyl or aroyl group substituted by at least one substituent chosen from halogen atoms and C^-Cg alkoxy groups; more preferably at least one of Ri to R5 is an unsubstituted or substituted phenyl, benzyl or benzoyl group.

Alternatively, Rj to r5. which may be identical or different, are each a hydrogen atoa or an unsubstituted or substituted cl-c6 •ikyi group.

In a still more preferred embodiment, X is a Cj-Cg alkyl, C3-C6 alkyl, C3-C6 cycloalkyl, aryl or — aralkyl group substituted by at least one substituent chosen from halogen atoms and Cj-Cg alkoxy groups; a -O-Rg group wherein Q is 0 or S and Pg is a Cj-Cg alkyl, Cj-Cg cycloalkyl, aryl, aralkyl, acyl, thioacyl, alkyloxythioyl, aryloxythioyl or aralkyloxythioyl group substituted by at least one substituent chosen froa halogen atoms and C^-Cg alkoxy groups; or a ~NRgR$ group wherein at least one of Rg and Rg, which may be identical or different, is a C^-Cg alkyl, C^-Cg cycloalkyl, aryl or aralkyl group substituted by at least one substituent chosen from halogen atoms and C^-Cg alkoxy groups or Rg**Rg together form a single divalent hydrocarbon group containing froa 3 to 6 carbon atoss, it being possible for one of the carbon atoms in the . hydrocarbon group to be replaced with an oxygen, sulphur or nitrogen aton:, substituted by at least one substitjent selected from halogen atoms, and unhalogenated or halogenated C^-Cg alkyl or C^-Cg alkoxy groups and a hydroxy group. ' """"^•^ ' • '" 230531 - ISC - Xt is also preferred that Hal 1 and Hal 2, which may be identical or different, are each a chlorine or bromine atom, and/or that Y is a halogen aton such as chlorine and n is 1, 2 or 3.

Examples of suitable compounds are 1-12- (2,4-dichlorophenyl)-2-hydroxy-4,5-dibroraopentylJ(1H)-1,2,4-triazole, 112-(2,4-dichlorophenyl)-2-hydroxy-4,5-dichloropentyl J (1H)],2,4-triazole, 1-12-(4-chlorophenyl)- 2-hydroxy-4,5-dichloropentyl] (1H)1,2,4-triazole, 1-12- (2,4-dichlorophenyl)-2-hydroxy-3-jaethyl-4,5-dibromo-pentyl)(1H)1,2,<-triazole or 1-12-(2,4-dichlorophenyl)- 2-hydroxy-3-*ethyl-4,5-dichloropentylJ-<1H)1,2,4-triazole.

In a further aspect, the invention consists in a process for the preparation of a compound of foraula lie as defined above which comprises reacting a compound of foraula lid: Sid in which Tr, la. A, Xj and Rj to R5 are as defined above with a aolecular halogen or aixed halogen in a solvent and, if desired, converting the coaoound obtained to an agriculturally acceptable salt or complex thereof.

As indicated above, tho compounds of the present invention are useful as intermediates in the preparation of compounds of formula I. Such compounds are themselves useful**-as fungicides.

'AUs*9O> —.—a— - 230551 o - X5D - The conpounds of foraula I aay be "O used for the preventive as well as curative control of 20 fungi, especially of the basidiomycetes, ascomycetes, adelomycetes or fungi imperfecti,,in particular rusts, mildew, cercosporella diseases, fusarium diseases, helminthosporium diseases, septoria diseases and rhizoctonia diseases of crops and of plants in general 25 and, in particular, of cereals such as wheat, barley, rye, oats and their hybrids and also rice and Baize. The compounds according to the invention are active, in particular, against fungi, especially of the basidioaycetes, ascomycetes, adelomycetes or fungi imperfecti type such as Botrytis cinerea, Erysiphe graainis, Puccinia recondita, Piricularia oryzae, Cercospora beticola, Puccinia V. i, J- J... n 230531 - ts - striiforais, Erysiohe cichoracearua, Fusariua oxysporua (aelon i s) , Py renoohora avena9, Sep tor i a tr i t ic i# Vencuria inasaualis, Whetzelinia sc lerot ioruo, .Manilla laxa# Nyco-sphaerella fijiensis, Marssonina panetcaniana, Alternaria 5 solani, Aspergillus niger, Cercospora arach»dicol a# Clado- ""v sporiua herbarua, Helainthosporiua oryzae, Penicilliua exoansun, Pestalozsia sp., Phialophora cinerescens# Phoaa betae# Phoaa foveata, Phoaa lingaa, Ustilago aaydis# Verti-ctlliua dahliae# Ascochyta pisi# Guignardia biduellii, ' 10 Corciciua rolfsii, Phoaopsis viticola# Sclerotinia sclerc-tiorua, Sclerotinia ainor, Coryneua c-ardinale and Rhisoc-tonia solani.

They also possess activity egaisst "the following fungi: Acrostalag^us koningi# the Alternaria# 15 the Colletotrichua, Corticiua rolfsii# Oiplodia natalensis# Gaeuaannoayces graainis# Gibberella fujikuroi# Horaodcndron cladosporioides# Lcntinus degener or tigrinus# Lenrites quercina# Heanoniella echinata# flyrotheciua vtrrucaria# Paecyloayces varioti# Pellicularia sasakii, Phellinus w 20 aegaloporus# Polystictus sanguineus# Poria vaporaria# Sclerotica rolfsii# Stachybotris atra# the Stereua# Stilbua sp.# Tranetes trabea# Trichoderaa pseudokoningi and Tr~ichothec iua roseua.

The conpounds of foraula I are of special in-25 terest because of their broad spectrua as regards cereal diseases (aildew, ruse# eyespoc, net blotch# leaf spot and foot rot). They are also of soecial interest because of 2305 31 their effectiveness against grey mould (Sotrycis) and cercospora diseases and, because of this, they nay be applied on crops as varied as grape vine, vegetable cross and tree crops and tropical crops such as peanut, banana, coffee, pecan nut and others.

In addition to the applications already described above, the products of formula I additionally have an excellent biocidal activity with respect to many other kinds of aicroorganisas, among which there may be 10 mentioned fungi such as those belonging to the genera: Pullularia such as the species P. pullulans, Chaetorniua such as the species C. globosum, Aspergillus such as the species Aspergillus niger, 15 Coniophora such as the species C. puteana.

Owing to their biocidal activity, the products of formula l make it possible to control effectively microorganisms whose proliferation gives rise to numerous problems in the agricultural and industrial fields. 20 To this end, they are particularly well suited for the protection of plants or of industrial products such as wood, leather, paints, paper, ropes, plasties and industrial water circuits.

They are particularly well suited for the pro-25 tection of Iignocellulose 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 230531 fencing, vine stakes or railway sleepers.

The compounds of formula I, 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, aercaptobenzothiazole, and insecticides such as pyrethroids or organochlorine compounds.

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

They are advantageously applied at doses of 0.005 to 5 kg/ha, and more specifically 0.01 to 0.5 kg/ha.

In practical use, the compounds of formula i ■ • are rarely used alone. Host often they form part of compositions. The invention of NZ 220050 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 coapound of general foraula I or a salt thereof or an addition complex thereof with a aetal salt in association with an agriculturally acceptable carrier. The coapositions generally also coaprise an agriculturally acceptable surfactant. Conventional inert carriers and conventional surfactants can be used. 250551 The ters "carrier", in the present description# denotes a natural or synthetic,organic or inorganic aaterial, with which the active substance is coabined in order to facilitate its application to the plant, to seeds or to the soil. Therefore, this carrier is generally inert anc it aust be acceptable in agriculture, especially on the treated plant. The carrier aay be sol id(e.g. clays, natural or synthetic silicates# silica, resins, waxes ana solid fertilizers,) or liquid (e.g. water, alcohols, ketones, petroleua fractions# aromatic or paraffinic hydrocarbons# chlorinated hydrocarbons and liquefied gases).

The surfactant aay be an eaulsifier# dispersant or wetting agent of ionic or non-ionic type. For exaaple# there nay be aentioned polyacrylic acid salts# Iignosulphonic acid salts# phenolsulphonic or naphthalene-sulphonic acid salts# polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty aaines# substituted phenols (especially alkylphenols or arylphenols)# sulphosuccinic acid ester salts# taurine derivatives (especially alkyltaurates)# phosphoric esters of alcohols or of polycondensates of ethylene oxide with phenols. The presence of at least one surfactant is general ly 'indispensable when the active substance and/or t.ie inert carrier are insoluble in water and the vector a g « ~ ; for the application is water.

Therefore# for their application# the coapounds of foraula (I) are generally in the fora of coopositions; 2305 31 these compositions according to the invention are thea-selves in fairly diverse solid or Liquid foras.

As solid foras of coapositiqns, there aay be aen-t ioned powders for dusting or scattering (with a content 5 of the coapound of foraula (I) up to 100%) and pellets, especially those obtained by extrusion, by coa-pacting, by iapregnation of a granulated carrier, or by granulation starting froa a powder (the content of the coapound of foraula (I) in these pellets being front 1 10 to 80! in these latter cases).

As liquid foras of coapositions, or foras intended to constitute Iiquid coapositions when applied, there aay be Mentioned solutions, especially water-soluble concentrates, eaulsifiable concentrates, eaulsions, flowables, 15 aerosols, wettable powders (or powder for spraying) and pastes.

The eaulsifiable or soluble concentrates aost frequently contain 10 to 80S of active substance, whereas the eaulsions or solutions ready for application contain, for 20 their part, 0.01 to 20X of active substance.

These coapositions aay also c on t a in other types of ingredients such as, for exaaple, protective colloids, adhesives, thickeners, thixotropie agents, penetrants, stabilizers and sequestering agents, as well as 25 other known active substances with pesticidal properties (especially insecticidal or fungicidal properties) or properties which proaote plant-growth (especially fertilizers) or plant growth regulating properties. More generally^ the coapounds according to the invention aay be contained with solid or liquid additives which correspond to the usual techniques of foraulation. for example, in addition to the solvent, the eaulsifiable concentrates may contain, when necessary, 2 to 202 of suitable additives such as the stabilizers, surfactants, penetrants, corrosion inhibitors, colouring agents or adhesives mentioned above.

In the case where the coapounds of foraula i i .. are used as fungicides, the'doses to be used aay vary within broad liaits according, in particular, to the virulence of the fungi and the cliaatic conditions.

In general, coapositions containing 0.5 to 5,000 ppa of active substance are very suitable; these values apply to the coapositions ready for application. Ppa denotes "parts per aillion". The range froa 0.5 to 5,000 ppa corresponds to a range froa 5 x 10"^ to 0.52 (percentages by weight).

As regards coapositions which are suitable for storage and transoortation, they aore advantageously contain froa 0.5 to 952 (by weight) of active substance.

Thus, the coapositions for agricultural use according to the invention o£ nx 220050 nay contain the active substances according to the invention within very broad liaits, ranging froa 5.10~^2 to 952 (by weight).

By way of exaaple, the coapositions of soae o 230531 concentrates are given below: unless otherwise specified percentages are by weight.

Example F (foraulation) 1 Active substance , 400 g/litre Alkali aetal dodecyl bensenesulphonate 24 g/litre :1 ethylene oxide/nonyIphenol condensate 16 g/litre Cyclohexanone 200 g/litre Aromatic solvent q.s. 1 litre According to another foraula for an eaulsifiable ^ concentrate/ the following are used: Exaaple F 2: * Active substance 250 g « Epoxide-treated vegetable oil 25 g Mixture of alkylarylsulphonate, poly-15 glycol ether and fatty alcoh.ols 100 g 0iaethylforoaaide 50 g Xylene 575 g Froa these concentrates/ by dilution with water, it is possible to obtain eaulsions of any desired concen-20tration, which are especially suitable for application on leaves.

Flovables/ which can also be applied by spraying/ are prepared so as to obtain a stable fluid product which does not settle; they usually contain froa 10 to 752 of 25active substance, fros 0.5 to 152 of surfactants, froa 0.1 to 102 of thixotropic agents and froa 0 to 102 of suitable additives such as antifoaas, corrosion inhibitors, stabi-lirers, penetrants and adhesives, and, as a carrier, water _ ..... ...I. - . • -.• 230531 n op an organic liquid in which the active substance is of low solubility or insoluble: solid organic substances or inorganic salts may be dissolvedin the carrier to assist in preventing sediaentation, or as anti-freeres for 5 the water.

The vettable powders (or" powder for spraying) are usually prepared so as to contain 20 to 952 of active sub-seance, and they usually contain, in addition to the solid carrier, froa 0 to 52 of a wetting agent, froa 3 to 102 of 10 a dispersant, and, when necessary, froa 0 to 102 of one or ■ore stabilizers and/or other additives such as penetrants, adhesives, anti-caking agents or colouring agents.

By way of exaaple, various coapositions of wet-trble powders are given below:.

Exaaple F 3: Active substance SOS Calciua Iignosulphonate (deflocculant) 52 Isopropyl naphthalenesulphonate (anionic wetting agent) 12 Anti-caking silica 52 Kaolin (filler) 392 Another coaposition of powder for spraying, at 702 strength, uses the following constituents: Exaaole F L: Active substance 700 g Sodiuo dibutyl naphthalenesulphonate 50 g Condensation product of naphthalenesul- . «. — ,«.-(UJ011Bmw—■'-, A ., — —— 2305 31 phonic acid, phenolsulphonic acid and formaldehyde in proportions 3:2:1 . 30 g Kaolin _ 100 g Whitener 120 g Another conposition of powder for spraying, at 40X strength, uses the following constituents: Exaaple F 5: Active substance 400 g Sodiua Iignosulphonate SO g Sodiua dibutylnaphthalenesulphonate 10 g Silica ' 540 g Another conposition of powder for spraying, at 25X strength, uses the following constituents: Exaaple F 6: Active substance 2S0 g Calciun Iignosulphonate 45 g Mixture of whieener and hydroxyethyl- cellulose -in equal parts by weight 19 g Sodiua dibutylnaphthalenesulphonate 15 g Silica 195 g Vhitener 195 g Kaolin 281 g Another coaocsition of powder for spraying, at 2S2 strength, uses the following constituents: 25 Exaaple F 7: Active substance 250 g Isooctylphenoxy-polyoxyethylene-ethanol 25 g n 230531 Mixture of whitener and hydroxyethyl-cellulose in equal parts by weight 17 g Sodiua aluainosilicate 543 g Kieselguhr 165 g Another conposition of powder for spraying, at * strength, uses the following constituents: Exaaple f 8: Active substance 100 g Mixture of sodiua salts of sulphates 10 of saturated fatty acids 30 g Condensation product of naphthalene-' sulphonic acid and forsaldehyde 50 g Kaolin 820 g To obtain these powder*, for spraying or uettable 15 powders*, the active substances are intiaately aixed in suitable nixers with the additional substances, and the aixtures are ground in aills or other suitable grinders. Powders for spraying are thereby obtained, the wettability and susoendability of which are advantageous; they aay 20 be suspended in water at any desired concentration and these suspensions aay be very advantageously used, especially for application on plant leaves.

Instead of the wettable powders, pastes can be produced. The conditions and aeans of production and use 25 of these pastes are siailar to those for wettable powders or powders for spraying.

As already stated, the dispersions and aqueous i % ■- • *—»W /—N 230531 enulsions, for exaaple the coapositions obtained by diluting with water a wettable powder or an eaulsifiable concentrate according to the invention, are included within the general scope of the present invention. The eaul-5 sions can be of the water-in-oil or oil-in-water type, and they nay have a thick consistency like that of "nayon-na ise".

Granulates intended for placing on the soil are usually prepared so as to be between 0.1 and 2 ■■ in size, 10 and they nay be aanufactured by aggloaerat ion or iapreg-nation. In general, the granulates contain 0.5 to 25% of active substance and 0 to 102 of additives such as stabilizers, slow-release aodification agents, binders and solvents.

'According to an exaaple of a. granulate conposition, the following constituents are used: Exaaple F 9: Active substance 50 g Epichlorohydrin 2.5 g Cetyl polyglycol ether 2.5 g Polyethylene glycol 3S g Kaolin (particle size: 0.3 to 0.8 an) 910 g.

In this particular case, the active substance is aixed with epichlorohydrin and dissolved in 60 g of ace-25 tone; polyethylene glycol and cetyl polyglycol ether are then added. The kaolin is wetted with the solution obtained and the acetone is then evaporated under vacuus. <5 230531 A microgranulate cf this type is advantageously used to control soil fungi.

The coapounds of foraula (I) aay also be used in the form of powders for dusting; a coaposit ion containing 5 SO g of active substance and 950 g of talc can also be used; a composition containing 20 g of active substance, 10 g of finely divided silica and 970 g of talc aay also be used; these constituents are aixed and ground, and the mixture is applied by dusting.

Examples I to VI! illustrate particular methods of preparing both the coapounds according to the present invention as well as the coapounds of NZ 220050.

• Exaaple I: Preparation of 1-C4-broao-2-(2,4-dichloro-phenyl) tet rahydrof ur an-2-y laethyl 3-1H-1,2,4-tr iarole. 15 Coapounds Nos. 1a,1b and 1a ♦ lb Stage a) Preparation of 1-chloro-2-(2,4-dichlorophenyl) 4-penten-2-ol: An organoaagnesiua derivative is prepared by add-•""■n ing a solution of allyl broaide (110 cc) in eehyl ether (7Q0 cc) and tetrahydrofuran (200 cc) with aagnesiua (110 g), between 15 and 20°C, over three hours. The aixture is refluxed for 30 ain and decanted, and the residue is washed with ether.

A solution of aloha,2,4-trtchloroacetophenone O (175 g) *n tetrahydrofuran (250 g) at -30°C is added to this organic phase and the mixture is neutralized with acetic acid. This is washed with water, dried over sodiua sulphate, concentrated and then distilled under vacuum. » colourless oil is obtained (205 g). B.p. (3.10~*mm Hg) = 140-142°C.

Stage b) Preparation of 1-C2-(2,4-dichlorophenyl)-2-hydroxypenten-4-yl3-lH-1,2,4-triazole A mixture of the product obtained in stage a) (106 g), triazole (55 g) and potassium carbonate (160 g) is heated in dimethylformamide (600 cc) .at 120° for four hours. The insoluble materials are filtered and washed with dimethylformaaide, and the reaction mixture is concentrated under vacuum. The res.idue, 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, a.p. 101°, is isolated (97 g).

Stage c) Preparation of the compounds No. 1a and No. 1b The compound obtained in stage b (35 g) in chloroform (200 cc) is treated with bromine at 0°. After decolorizing, the solvent is evaporated and the residue re-dissolved 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 n 230 5 31 of two diastereoisoaers in substantially equal propor-r""\ tions. Using silica coluan chroaatography, the least polar isoaer No. 1a: white crystals a.p. 83°, and then the nost polar isomer No. lb: white crystals a.p. 94°, 5 are isolated in sequence. After recrystalIization, la, w- a.p. 96 and lb, a.p. 104°, are obtained. The 50:50 aixture of la and lb has a Belting point of 74°.

The following coapounds were prepared in the saae way, using the appropriate raw Materials: 1-C4-broao-2-(4-10 chlorophenyl)tetrahydrofuran-2-ylaethyl)-1H-1,2,4-triazole: 1c: n.p. 74°; 1d: a.p. 78° and 1c*d: a.p. 69°.

Exaaple II - Preparation of 1-C2-(2,4-dichlorophenyl)-4-hydroxytetrahydrofuran-2-yInethy13-1H-1,2,4-tr iazole. Coapounds No. 2a and No. 2b.

The isoaer (10 g) la of ExaMPle I, which is the ""~v least polar isoaer, dissolved in chlorobensene (30 cc), is refluxed for 48 h, in the presence of sodiua benzoate (20 g) in water (30 cc), and the phase transfer catalyst "A0OGEN 464" aethyltrialkylaaaoniua chloride (1g). 20 After diluting with ether, the organic phase is washed with water and reduced under vacuua. The residue is then treated with aethanol (100 cc) in the presence of potass iua hydroxide (7 g) at reflux teaperature for 3 hours.

« The aixture is cooled, diluted with water and extracted 25 with ethyl acetate, and the product washed to neutrality and purified by chroaatography, the crude product being obtained after concentration under vacuua. The alcohol 2a is 230531 isolated in the fora of a whit? powder C2.S g), a.p. 193°.

Operating in she saae way, starting froa the most polar isoaer 1b obtained according -to Exaaple I, the optically active alcohol 2b is obtained in the fora of a 5 white powder, a.p. 162°C. The 50:50 aixture of 2a and 2b is an oil.

Exaaple III - Preparation of 1-C2-(2,4-dichlorophcnyl)-4-etho»ytetrahydrofuran-2-ylaiethyl3-1H-1#2^4-triagole. Conpounds No. 3a and No. 3b.

The alcohol 2a (2.2 g) dissolved in diaethylsul- phoxide (12 cc) is treated, in seauence, with 80S strength sodiua hydride (0.42 g) and then with ethyl iodide (1.15 cc). After 15 ainutes, the aediua is diluted with water and extracted with ethyl acetate.. After washing with 15 water, the solvent is evaporated and the residue is purified by silica coluan ehroaatography to obtain a colourless oil which is the isoaer 3a which crystallizes on trituration with pentane a.p. 90°; in the saae way, starting with 2b, the isoaer 3b, which is a white powder, a.p. 63°, 20 is obtained. The 50:50 aixture of 3a ♦ 3b is an oil. The coapounds of foraula VIII listed in the following table were obtained in the saae way, using the appropriate bili.4-? or = :: I . 230531 No. xi Melting Point <a H 0-C-* (phenyl) 0 98 4b 0C-* (phenyl) 0 H 1<0 Sa .

H OCH, oil 5b 0-CHj H oil 6a K O-n-Pr oil 6b 0-n-Pr K oil Extaolc IV - Preparation of 1-C2-(2,4-dichloroohenyl)-4-ethylthiotetrahydrofuran-2-ylaethyU-lH-1,2,4-triazole. Coapounds No. 7a and Ho. 7b The broaide la (3.8 g) dissolved in diaethyl sul-15 phoxide (38 cc) containing water (2 cc) is treated with sodiua hydrogen sulphide (2.8 g) for 2 hours. Poudered potassiua hydroxide (3.3 g) is then added, followed by ethyl iodide (4 cc). After 10 ainutes of stirring, the aediua is diluted with water and extracted with ether. 20 After drying and evaporation, the isoaer 7a, which is a yellow oil (3.9 g), a.p. 88°, is obtained.

Operating ir. the saae way, starting with 1b, 7b is obtained in the fora of a pale yellow powder, a.p. 64°. The aixture of isoaers is an oil. The coapounds of foraula 25 VIII listed in the following table were obtained in the saae way, using the appropriate thiols: 230 5 o1 No. • • *2 m Melting point ; 1 I 8a H </> 1 0 x w 96 8b S-CH3 K oil 9a H S-n-Pr 110 9b S-n-Pr H 0 il 10a H S-2-ClEt 127 ' . 10b r S-2-ClEt H 1 oil 11a H S-i-Bu 68 lib S-i-Bu H oil 12a H S-i-Pr 75 12b S-i-Pr H 65 Exaaple V - Preparation of 1-C8-<2,4-dichlorophenyl)-1 ,4,7-tr iox&SP iroC4.4 3nonan-8-y laethyl 3- 1H-1,2, 4-triazole. Coapound No. 13 Stage a) Preparation of 1-chloro-2-(2,4-dichlorophenyl>-. 3,4,5-pentanetriol.

The chlorohydrin obtained in stage a) of Exaaple 1 (91 g) is epoxidized in 1,2-dichloroethane (125 cc) in the presence of vanadyl acetylacetonate (5 g) and 702 strength tert-butyl peroxide (200* cc) by heating at the reflux tea-perature for 48 hours. The cooled aediua is diluted vith water, washed several tiaes with a sodiua bisulphite solution and then concentrated. The residue is then converted 2305 31 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 aediua is extracted with toluene (300 cc) and then concentrated.

Stage b) Preparation of 2-(2,4-diehlorophenyl)-2-chloro-ae thyIte trahydrofuran-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 g), with the 10 separation of the water foraed. After evaporating the re- m action aediua, the residue is chroaatographed on a silica coluan (40:60 ethyl acetate/heptane eluant) to obtain a colourless oil (14.5 g) corresponding to a aixture of alcohol diastereoisoaers, naaely 2.-(2,4-dichlorophenyl)-15 4-hydroxy-2-chloroaethyItetrahydrofuran. This product is directly oxidised with chrooic anhydride In acetic acid to obtain, after purification by silica coluan ehroaatography, furanone in the fora of white crystals, a.p. 99°C.

Stage c) Preparation of 7-chloroaethyl-7-(2,4-dichloro-phenyl)-1,4,6-tr ioxaspiroC4.43nonane.

The furanone obtained in stage b) (4.2 g), in toluene (50 cc), is heated at reflux teoaerature in the presence of ethylene glycol (6.5 cc) and p-toluenesulphonic 25 acid (0.1 g), with the separation of the water foraed, until the disappearance of the starting product.

The aediua -is washed with sodiua hydroxide and 'vYewiiesW^Lik. " " ■ • --— 230 5 then diluted with water, extracted with ether and concentrated. A white solid (5.1 g), b.d. 99°, is obtained.

Stage d) Preparation of coaoound 13 The halide of stage c) (5 g) in diaethyl sulphoxide 5 (20 cc) is heated to 170° in the presence of triazol/l sodiua (2.75 g) for 6 hours. The aediua is poured into water, extracted with ethyl acetate, concentrated and purified by silica coluan ehroaatography. After recrystalli-zation in an ethyl acetate/heptane aixture, pale yellow 10 crystals (3.6 g>, a.p. 123°, are isolated.

Exaaple VI - Preparation of 1-C4-chlo1ro-2-(2,4-dichloro-phenyl)-tetrahydrofuran-2-ylaethyl3-1H-1,2#4-triasole. Coapounds No. 14a and No. 14b Stage a) Preparation of 2-(2,4-dicblorophenyl)-1,4,5-15 triehloro-2-pentanol.

The chlorohydrin obtained in stage a) of Exaaple I dissolved in diehloroaethane (150 ec) is treated with gaseous chlorine (13.4 g) at -15°. The aediua is then treated with a 372 strength sodiua bisulphite solution 20 (15 cc), washed with water, dried and then evaporated. • A crude product in the fora of a colourless oil (49.7 g) containing aoproxiaately 702 of the desired product in the fora of a aixture of two diastereoisoaers is obtained.

Stage b) Preparation of 1-(2,4-dichlorophenyl )-1-(2,3-25 dichloro-1-propanyl)oxirane A first aethod consists in dissolving the crude chlorohydrin (10.3 g) obtained in stage a) above in aethanol (30 cc) and treating it with a solution of meth-anolic potassiua hydroxide (12 cc) at a concentration of 2.55 * 103 moles/litre, at aabient temperature. The ore- «* cipitate is filtered and the methanolic solution is evapor-5 ated under vacuum. The residue is purified by silica coluan ehroaatography. A colourless oil is obtained (7.4 g).

A second aethod consists in dissolving the chlorohydrin (19.9 g) obtained in stage a) of Exaaple I in aethanol (75 cc), and treating it with a potassiua hydro-10 xide (4.9 g) solution in aethanol (20 cc) at aabient tea-perature. After the filtration of the'insoluble material and evaporation, epoxide (17.1 g) is obtained in the fora of a yellow oil. This epoxide is treated with chlorine until the yellow eolour (10.1 g) persists at -15°C. The 1S aediua is then washed with a sodiua bisulphite solution followed by water, and then evaporated under vacuua. A yellow oil (20.8 g) consisting of a aixture of two diastereoisoaers in a ratio of 45:55 is obtained.

Stage c) Preparation of 1-C4-chloro-2-(2,4-dichlorophenyl) 20 tetrahydrofuran-2-ylaethyl3-!H-1,2,4-tr iazole The epoxide obtained in stage b) (61.7 g) in 1-butanol (0.5 litre) is heated at 90° for 6 hours in the presence of tria:olyl sodiua (18.6 g). The inorganic precipitate is filtered and the butanol is evaporated. The 25 residue is purified by silica coluan chromatography (482 ethyl acetate:48X heotane:4£ aethanol eluant) to obtain, in sequence, the first diastereoisoaer 14a, m.p., 113°, and then the second di-astereoisoaer Kb, m.p. 97°. The 50:50 mixture of 14a 14b has a melting point of 50°.

Exaaple VII Preparation of 1-C4-o»o-2-(2,4-dichlorophenyl)tetrahydro-furan-2-ylaethyl3-lH-1,2,4-triatole. Coapounds 15 and 20 The alcohol 2a (37.7 g) is added ac -60°C to a solution of dimethyl sulphoxide (17 cc), in dichloroaethane (120 cc), treated at -60° with a solution of trifluoro-acetic anhydride (25.4 cc) in dichloroaethane (60 cc).

After aaintaining at ->60° for half an hour, the temperature is allowed to rise to aabient temperature and triethylaaine % (48 cc). The aediua is poured into water, extracted with dichloroaethane and evaporated. A white powder (a.p. 91°) is isolated by crystallisation in ether.

A aixture of ketone 15 (3.1 g), phosphorus penta-chloride (2.3 g) and dichloroaethane (30 cc) containing triethylbenzylaaaoniua chloride (0.25 g) is stirred for 2 hours at aabient teaperature until the starting aaterial disappears. The aediua is evaporated, diluted with water (100 cc), neutralized with sodiua bicarbonate and extracted with ether. After drying and evaporation, the oily residue is recrystallized in isopropyl ether (twice). A white powder (0.6 g), a.s. 138°, is obtained. 1-C4,4-dichloro-2- (2,4-dichlorophenyl) tetrahydrofuran-2-ylnethyl3-iH-1,2,4- triazole, coapound No. 20.

Example VIII - Preparation of 1-C4-diaethylaaino-2-(2,4-dichloroohgnyl)tetrahydrofuran-2-ylaethyl3-1H-1,2,4-triazole. Compound 16 The ketone of example III and then sodiua cyano-borohydride (0.24 g) are successively added ee a solution of potassium hydroxide (0.24 g) and diaethylamine hydrochloride (1.05 g) in aethanol. After 15 hours, the aediua is diluted with water and extracted with ether. The desired product is then extracted froa the organic phase with 6N hydrochloride acid (3 x 20 al). After neutralization, extraction and silica coluan ehroaatography, coapound No. 5 (1.6 g) is isolated in the fora of a pale yellow oil (50:50 aixture of 2 isoaers).

Exaaple IX - Preparation of 1-C4-aethoxyiaino-2-(2,4-d ichloropheny I)tetrahydrofuran-2-ylaethyl3-1H-1,2,4-triazole. Coapound 17.

The ketone of exaaple III (2g) in ethanol (30 ec) is heated under reflux in the presence of aethoxylaaine hydrochloride (5.8 cc of a 255 solution in water) for 2. hours. The aediua is diluted with water, extracted with dichloroaethane and evaporated. The product is isolated by crystallization in a aixture of diisopropyl ether and heptane, in the fora of a white powder, a.p. 103° (aixture of the two geoaetric isomers).

Exaaple X The coapounds in which R^j = H (4-hydroxyiaino) a.p. » 195° 18 r\ 250531 ^11 5—^ (4-isooroooxyiaino) oil 19 were prepared in the saae Banner.

Exaaple X and those which fallow illustrate the fungicidal applications of the conpounds according to the 5 invention.

In these exanples, the sprayings 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 10 on average to the application of approxiaately 2 aicrograss * of active substance per cn^ of leaf area of the plant.

Under the conditions of Exaaple X and those which follow, the coapounds illustrated showed no phytotoxicity.

In these Exaaples, a product, is regarded as pro-15 viding coaplete protection against a fungal disease when the protection is at least 952; the protection is regarded as good when it is at least 80* (but less than 952), as fairly good when it is at least 702 (but less than 802) and as average when it is at least 502 (but less than 702). 20 Inthepresent specification, the percentages are except where otherwise indicated and except those relating to yields, percentages by weight. In the case where ths percentages are expressed relative to the s.toichioaetry, these are aolar percentages. As regards concentrations, 25 soae of these are expressed in ppa (part per aillion) which corresponds to ag/litre. 230531 Example XI - In vivo test on Sotrytis cinerea on toeats An acueous eauIsion of the active substance to be tested, having the following coaposition, is prepared by fine grinding: active substance under test: 60 ag Tween 80 (surfactant consisting of an oleate of a polycondensate of ethylene oxide with a sorbi-tan derivative) diluted to 102 strength in water: 0.3 cc the voluoe is aade up to 60 cc with water.

This aqueous eaulsion is then diluted with water to obtain the desired concentration. - to 40-day-old, greenhouse-cultivated toaatoes (variety Naraande) are treated by spcaying with diluted aqueous exulsions (called slurries) as defined above and at vzLrious concentrations of the compound to be tested. The trial is replicated twice with each concentration.

After 24 or 48 hours, the leaves are cut and placed in 2 Petri dishes (diaaeter 14 cb) the base of which has previously been provided with a disc of aoist filter paper (S leaflets per dish).

The inoculuo is then applied by aeans of a syringe by depositing droos (3 droos per leaflet) of a soore suspension. This suspension of Botrytis cinerea spores was obtained froa a 15-day-old culture, which was then suspended in a ni/trient solution (100,000 units/cc).

Verification is carried out 3 and 6 days after — ^— 23 0 5 Che inoculation by comparison with an untreated control.

Under these conditions, at a dose of 1 g/litre, a good or total protection is observed with coapounds 1a, 1b, la ♦ lb, 3b, 5b, 6b, 8b, 9b, 12b, 14a, 14b, 14a * 14b 5 and 17.

Exaaple XII - In vivo test on Erysiphe "graainis on barley (barley Mildew) Barley, in pots, sown in plain soil, is treated at the 10 ca height stage by spraying with an aqueous 10 eaulsion (called slurry) at the concentration indicated below. The trial is replicated twice. After 24 hours, the barley plants are dusted with Erysiphe graainis spores, the dusting being carried out using diseased plants.

Readings are taken 8 to 14 da.ys after inoculation. 15 Under* these conditions, the following results are observed: at a dose of 1 g/litre, good or total protection with 1a, 1b, 1a ♦ 1b, 2a, 2b, 3a, 3b, 3a ♦ 3b, 4a, 4b, 5a, Sb, 6a, 6b, 7a ♦ 7b, 8a, 8b, 13, 14a 14b, 14a ♦ 14b, 15, 17, 19.

Exanole XIII - In vivo test on "Puccinia recondita" respon-sible for wheat rust Vheat, sevn in plain soil in pots, is treated at the 10- era height stage by spraying with diluted aqueous eaulsions of the sane conposition as that described 25 in Exaaple VIII and at various concentrations of the coapound to be tested. The trial is replicated twice at each concentration. o 230531 After 24 hours, an aqueous suspension of spores C5Q,QQQ sp/cc) is sprayed onto the wheat; this suspension was obtained froa contaminated plants. The wheat is then placed for 43 hours in an incubation cell a: appro*iaately 5 18°C and at 1002 relative humidity.

After these 2 days, the relative huaidity is lowered to 602. 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 coapounds 1a, lb, 1a * 1b, 3a, 3fc, 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" responsible for rice blast Riee,*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 eaulsion defined above at the concentration indicated below. The trial is repeated ewice. After 48 hours, treatment is ^ 20 carried out by applying on the leaves a sussension of spores obeained 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 protec-25 tion with coapounds la, lb, la * lb, 3a, 3b, 6a, 8a, 8b, 9a, 9b, 10b, 11a, 11b, 12a, 12b, 14a, 14b, 14a * Kb and 15. o 230 5 o I I - 42 - Exaaple XV - In vitro test on seed fungi and soil fungi The action of the coasounds according to the invention is studied on the following fungi responsible for diseases of cereals and other plants: 1) Pyrenophorae avenae 2) Septoria nodoruo 3) Helm inthosporiua teres 4) Fusariun roseua ) Fusariun nivale 10 6) Fusariun culaorua 7) Rhizoctonia cerealis 8) Septoria tritici 9) Botrytis cinerea sensitive to carbendaziae and to cyclic iaides * 10) Botrytis cinerea resistant to carbendaziae and to cyclic iaides 11) Pseudocereosporella herpotrichoides 12) Fusariun oxysporua F. sp. aelonis 13) Rhizoctonia solani 14) Helninthosporiua graaineua The nuabers which appear before the naaes will be used to represent these fungi in Table (11).

- For each trial, the procedure is as follows: a nutrient aediua consisting of potato, glucose and agar 25 (POA aediua) is introduced susercooled into a series of Petri dishes (20 cc per dish) after sterilizing in an autoclave at 120°C. 230531 In the course of filling the dishes, an acetone solution of the active substance is injected into the supercooled aediua, to obtain the desired final concentration.

Petri dishes similar to the above, into which are poured siailar Quantities of a nutrient aediua 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 10 of the saae fungus.

The dishes are stored for 2 to 10 days (depending on the fungus being tested) at 22°C, and the growth of the fungus in the dishes containing the active substance to be tested is coapared with that of the. saae fungus in the 15 dish used as the control.

For each coapound tested, the degree of inhibition of the fungus considered, at a dose of 30 ppa, is thus deterained. The results are given in the following table.

Ci - 23 0 5 3 1 r\ Ccapcunc | No. . 1 2 3 Funs: 1 * 6 1 7 | la | 100 100 100 1 95 100 100 95 I lb ( 100 90 100 1 100 100 100 90 | la + lb! 100 95 100 1 95 100 100 90 | 2a | 50 95 80 1 50 80 100 80 | 2b I 80 110 80 I 50 90 90 80 | 3a 1 95 90 100 1 50 80 80 90 | 3b ( 95 95 100 1 80 90 100 90 | 3a 4- 3b I 80 0 80 1 o 80 80 80 | 4a I 90 0 90 1 80 80 90 90 | 4b | 95 80 95 I 80 80 100 90 | 5a I 50 90 50 1 50 50 50 50 | 5b | XOO 100 . 100 1 90 95 100 95 | 6a 1 50 90 50 1 50 50 * 50 50 | 6b | 100 95 95 I 80 90 90 90 | 7a | .95 95 95 1 o 0 0 50 | 7b I 95 90 95 1 o 0 0 50 | 7a + 7b1 50 95 50 1 o 0 0 50 | 8a 1 95 80 95 I 80 50 100 80 | 8b | 100 90 95 1 80 80 90 80 i 9a | 95 90 95 I 80 80 90 80 | 9b I 80 95 95 1 o 0 80 80 | 10a I 80 0 80 1 50 90 95 80 | 10b | 90 80 90 1 o 0 50 80 | 11a 1 90 50 95 1 o 0 0 80 | lib I 90 80 95 t o 0 0 80 | 12a I 90 80 95 I o 80 80 80 | 12b I 95 90 95 1 80 80 90 80 | 2305 31 Conoound| No. . 1 1 2 3 Fung i | 4 6 1 7 1 13a 1 — 1 90 — | — — — — | 14a 1 95 I 95 100 1 95 100 100 90 | 14b I 95 I 90 100 1 90 95~ 100 90 I 14a+14b| 100 1 95 100 1 1 0 100 100 95 1 1 0 I 95 80 i o 0 50 0 I 16 I SO 1 0 80 1 o 0 50 80 | 17 I 80 1 0 80 1 80 95 80 *0 I 18 I 1 1 I 19 I 90 1 0 80 I 80 90 50 80 I 1 90 | 80 95 | 9o 9S 90 90 | \ 230531 • n r•> Coeipouncf KO. - 8 9 F ung i 10 1 11 12 13 • I 14 1 la | 100 100 100 100 100 80 100 1 lb I - 95 95 100 100 80 1001 la + lb| 100 95 95 100 10Q 90 95 I 2a | 0 95 95 100 0 0 801 2b ( 0 80 50 100 80 0 801 3a | 95 90 90 95 0 0 901 3b | 100 95 100 95 80 80 951 3a + 3b I 0 80 95 0 0 0 801 4a | 0 95 95 0 0 0 901 4b | 0 95 95 90 95 0 951 5a 1 0 0 0 100 0 0 501 5b I 0 95 90 100 95 90 901 6a 1 0 50 50 100 0 0 501 6b | 50 95 95 100 80 80 951 7 a I 0 95 95 95 0 80 801 7b | 0 90 95 90 0 50 50| 7a + 7b I - 95 95 100 50 80 501 8a I 0 80 80 80 80 80 951 8b | 0 95 95 90 80 80 951 9a | 0 90 90 90 80 80 951 9b | 0 95 90 100 80 80 501 10a I 50 80 0 0 0 0 0| 10b | 0 90 95 80 50 50 901 11a I 0 0 80 50 50 50 951 lib I 0 80 80 80 80 80 951 12a | 0 50 80 80 0 80 901 12b | 0 95 95 90 80 80 1001 13a | mm 0 0 100 50 0 - | ^w~- ri 230531 - Lt - Coinoound Fungi r> llv « | 8 9 11 12 13 14 I 14a | - 100 100 100 100 80 1001 14h | * 0 95 95 100 80 80 1001 I4a+14b| 50 95 95 100 100 80 95| I - 0 0 95 0 0 01 16 I 0 0 0 0 0 0 80| 17 I 0 80 80 0 0 0 80| 18 I 1 19 I 0 0 0 0 0 0 90| 1 0 80 90 100 50 80 90 | OR.

Tr or Im ~T«t3 Tr or Im EP 151084 (I) o 230 5 31 Ila -f- J lib lie R, Ilf I Tr or R3 R4 Im lid llg *5 II Tr R, "4 or Im J lie or Im 2305 31 in 11 lb IIIc or la O <* „«xi Ri Hie OH X. R.

Tr R3 or la IVa *? _ IV A\ / ° fr"*i iV" •Tr » p or ia "i 3

Claims (19)

« 2305 31 - 51 - - 52 - 230 5 31 WI-VT/^vVc CLAIM IS: -£^*§ 1 A compound which is a triazole or imidazole derivative of formula He: Tr or Im Hal 2 lie in which A is (CHj)- wherein Ph is a phenyl nucleus* m is 0 or

1 and n is 0 or an integer less than 6; each Y* which may be identical or different to each other Y if n is greater than 1, is a halogen atom, a cyano or nitro group or an unhalogenated or halogenated alkyl or alkoxy group; Tr is a 1,2,4-triazol-l-yl group and la is a 1,3-imidazol-l-yl group Rj to R^* which may be identical or different* are each a hydrogen atom or an unsubstituted or substituted Cj-Cg alkyl* C3-C6 cycloalkyl* aryl, aralkyl* Cj-Cg alkoxy* Cj-Cg alkanoyl or aroyl group; Xj is a hydrogen or halogen aton:; an unsubstituted or substituted Cj-Cg alkyl* C^-Cg cycloalkyl, aryl or aralkyl group; 2305 31 - 53 - a -Q-Rg group wherein 0 is 0 or S and Rg is a hydrogen a toe or an unsubstituted or substituted Cj-Cg alkyl, C^-Cg cycloalkyl, aryl, aralkyl, acyl, thioacyl, alkyloxythioyl, aryloxythioyl or aralkyloxythioyl group or a -nr^r^ group wherein R^ and Rj, which nay be identical or different, are each a hydrogen atom or an unsubstituted or substituted C^-Cg alkyl, Cj-Cg cycloalkyl, aryl or aralkyl group or Rfl and Rg may together form a single divalent hydrocarbon group containing from 3 to 6 carbon atoms, it being possible for one of the carbon atoms in the hydrocarbon group to be replaced by an oxygen, sulphur .or nitrogen atom, it also being possible for the hydrocarbon group to be substituted; and Hal 1 and Hal 2, which may be identical or different, are each a halogen atom; or an agriculturally acceotable salt thereof or complex thereof with a metal salt.

2. h compound according to claim 1 wherein m is 0.

3. A compound according to claim 1 or 2 which is a triasole derivative.

4. A compound according to any one of claims 1 to 3 wherein at least one of Rj to Rj, which may be identical or different, is a Cj-Cg alkyl, C^-Cg cycloalkyl, aryl, aralkyl, Cj-C^ alkoxy, Cj-Cg alkanoyl or aroyl group substituted by at least one substituent chosen from halogen atoms and Cj-Cg alkoxy groups.

5. . A compound according to any one of claims 1 to 4 - - - *.«*.«».».n-«T.wiu,— ,„ »"..,J »* «•-•— 230531 - 54 - wherein at least one of Rj to Rj is an unsubstituted or substituted phenyl, benzyl or benzoyl group.

6. A compound according to any one of claims 1 to 4 wherein Rj to R^, which may be identical or different, are each a hydrogen atom or an unsubstituted or substituted cl"c6 alkyl group.

7. A compound according to claim 6 wherein Rj to Rj are each a hydrogen atom.

8. A comoound according to any one of claims 1 to 7 wherein X, is a Cj-Cg alkyl, Cj-Cg cycloalkyl, aryl or aralkyl group substituted by at least one substituent chosen from halogen atoms and C^-Cg alkoxy groups; a -O-Rg group wherein 0 is O or S and Rg is a alkyl, cycloalkyl, aryl, aralkyl, acyl, thioacyl, alkyloxythioyl, aryloxythioyl or aralkyloxythioyl group substituted by at least one substituent chosen from halogen atoms and Cj-Cg /""s alkoxy groups; or a -NRgRg group wherein at least one of Rg and Rg, which »ay be identical or different, is a Cj-Cg alkyl, Cj-Cg cycloalkyl, aryl or aralkyl group substituted by at least one substituent chosen from halogen atoms and ,~s 'w C1~C6 a*koxy groups or Rg-Rg together form a single divalent hydrocarbon group containing from 3 to 6 carbon atoms, it being possible for one of the carbon atoms in the ' hydrocarbon group to be replaced with an oxygen, sulphur or nitrogen atom, substituted by at least one substituent selected from halogen atoms, and unhalogenated or halogenated Cj-Cg alkyl or C^-Cg alkoxy groups and a hydroxy 4B> group. 230531 - 55 -

9. A compound according to claim 8 wherein X is an unsubstituted or substituted phenyl or benzyl group or a -O-Rg group wherein 0 is 0 or S and Rg is an unsubstituted or substituted phenyl, benzyl, acetyl, thioacetyl, propionyl or thiopropionyl group.

10. A compound according to any one of claims 1 to 9 wherein Hal 1 and Hal 2, which nay be identical or different, are each a chlorine or bromine atom.

11. A compound according to any one of claims 1 to 10 wherein Hal 1 and Hal 2 are identical.

12. A compound according to any one of claims 1 to 11 wherein Y is a halogen atom and n is 1, 2 or 3.

13. A compound according to claim 12 wherein * is a chlorine atom.

14. A compound according to claim 12 or 13 wherein n is 1 or 2, and Y is in either an ortho and/or in the para position with respect to the ~(CH2)- group.

15. A compound according to claim 1 which is 1- (2-(2,4-dichlorophenyl)-2-hydroxy-4,S-dibromopentyl)(1H) -1,2,4-triazole# 112-(2,4-dichlorophenyl)-2-hydroxy-4,5-dichloropentyl ](lH)l,2,4-triazole, l-|2-(4-chlorophenyl)- jt 2-hydroxy-4,S-dichloropentyl)(1H)1,2,4-triazole, 1-12-(2,4-dichlorophenyl|-2-hydroxy-3-methyl-4,S-dibromo-pentyl](1H)1,2,4-triazole or 1- 12-(2,4-dichlorophenyl)- 2-hydroxy-3-*ethyl-4,S-dichloropentylJ - (1H)1,2,4-tr iazol e.

16. A process for the preparation of a compound as defined in any one of claims 1 to 15 which rirtrrriT-ji r . . - 56 - 2305 31 reacting a compound of formula lid: *i I! O C i 22d Tr cr Xia in which Tr, Im, A, Xj and Rj to R^ are as defined in claim 1 with a molecular halogen or mixed halogen in a solvent and, if desired, converting the comoound obtained to an agriculturally acceptable salt or coaplex thereof.

17. A process according to claia 16 substantially as described in Exaaple I or II.

18. A coapound as defined in any one of claims 1 to IS whenever prepared by a process as defined in claim 16 or 17.

19. A coapound which is a triazole or imidaxole derivative of foraula lie as defined in claim 1 substantially as herein described with reference to any exaaple thereof. O cs AG3at E. SON / £» o ,c- -