GB2218702A

GB2218702A - Fungicidal phenylacrylates

Info

Publication number: GB2218702A
Application number: GB8908699A
Authority: GB
Inventors: John Martin Clough; Christopher Richard Ay Godfrey; David Philip Bacon
Original assignee: Imperial Chemical Industries Ltd
Current assignee: Imperial Chemical Industries Ltd
Priority date: 1988-05-11
Filing date: 1989-04-18
Publication date: 1989-11-22
Also published as: GB8908699D0; GB8811116D0

Abstract

Novel compounds of formula: <IMAGE> and stereoisomers thereof, wherein A, B, X, Y and Z, provided that they are not all hydrogen, are independently hydrogen, halogen, hydroxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted acyloxy, optionally substituted amino, optionally substituted acylamino, nitro, cyano, -CO2R<1>, -CONR<1>R<2>, -COR<1>, -CR<1>=NR<2>, or -N=CR<1>R<2> or the groups A, B, X, Y and Z when they are in adjacent positions on a phenyl ring, join to form a fused ring, either aromatic or aliphatic, optionally containing one or more heteroatoms; and R<1> and R<2> are independently hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, optionally substituted aryl or optionally substituted aralkyl; and metal complexes thereof have fungicidal activity. Intermediates of formulae (VII) - (XI) herein used in the preparation of the compounds (I) are also novel compounds.

Description

FUNGICIDES This invention relates to derivatives of acrylic acid useful as fungicides, to processes for preparing them, to fungicidal compositions containing them, and to methods of using them to combat fungi, especially funqal infections in plants.

It is known from EP-A-0178826 that certain derivatives of acrylic acid can be used as fungicides. These include (E)-methyl 3-methoxy-2-(2 -phenylthio)phenylacrylate.

According to the present invention there is provided a compound having the general formula (I):

and stereoisomers thereof, wherein A, B, X, Y and Z, provided that they are not all hydrogen, are independently hydrogen, halogen, hydroxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted acyloxy, optionally substituted amino, optionally substituted acylamino, nitro, cyano, -CO2Rl, -CONR1R2, -COR1, -CR1=NR2, or -N=CR1R2 or the groups A, B, X, Y and Z when they are in adjacent positions on the phenyl ring, may join to form a fused ring, either aromatic or aliphatic, optionally containing one or more heteroatoms; and R1 and R2 are independently hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, optionally substituted aryl or optionally substituted aralkyl; and metal complexes thereof.

The compounds of the invention contain at least one carbon-carbon double bond, and are sometimes obtained in the form of mixtures of geometric isomers.

However, these mixtures can be separated into individual isomers, and this invention embraces such isomers and mixtures thereof in all proportions including those which consist substantially of the (Z)-isomer and those which consist substantially of the (E)-isomer.

The individual isomers which result from the unsymmetrically substituted double bond of the acrylate group are identified by the commonly used terms "E" and "Z". These terms are defined according to the Cahn-Ingold-Prelog system which is fully described in the literature (see, for example, J March, "Advanced Organic Chemistry," 3rd edition, Wiley-Interscience, page 109 et seq).

Usually one isomer is more fungicidally active than the other, the more active isomer being the one in which the groups -CO2CH3 and -OCH3 are on opposite sides of the olefinic bond of the acrylate group.

In the case of the compounds of the present invention this is the (E)-isomer. The (E)-isomers form a preferred embodiment of the invention.

The formula

used hereinafter signifies a separable mixture of both geometric isomers about the acrylate double bond, i.e.

Alkyl groups and the alkyl moiety of alkoxy groups can be in the form of straight or branched chains, and suitably contain from 1 to 6 carbon atoms; examples are methyl, ethyl, n- or iso-propyl and n-, sec-, iso- and t-butyl. Optional substituents of alkyl and alkoxy include halogen (especially fluorine and chlorine), hydroxy and alkoxy.

Alkenyl and alkynyl groups suitably contain from 2 to 6 carbon atoms in the form of straiqht or branched chains and, where appropriate, have either the (E)- or (Z)-configuration. Examples are vinyl, allyl, -C(CH3):CH2, (E)- and (Z)-crotyl and propynyl.

Optional substituents include halogen (especially fluorine and chlorine), hydroxy, alkoxy and optionally substituted aryl (especially phenyl) and heteroaryl (especially pyridyl, pyrimidinyl, pyrrolyl and thienyl).

The acyl moiety of acyloxy and acylamino groups includes C1-4alkylcarbonyl and benzoyl in which the phenyl ring is optionally substituted as hereinafter described.

Optionally substituted amino includes mono- and di-(C14 )alkylamino.

Aryl and the aryl moiety of aralkyl include naphthyl and especially phenyl. Optional substituents include one or more of the following; halogen, hydroxy, mercapto, C14 alkyl (especially methyl and ethyl), C24 alkenyl (especially allyl), C2-4 alkynyl (especially propargyl), C14 alkoxy (especially methoxy), C2-4 alkenyloxy (especially allyloxy), C24 alkynyloxy (especially propargyloxy), halo(C1-4)alkyl (especially trifluoromethyl), halo(C1~4)alkoxy (especially trifluoromethoxy), C14 alkylthio (especially methylthio), hydroxy(C14)alkyl, C14 alkoxy(C14)alkyl, C36 cycloalkyl, C3-6 cycloalkyl (C1-4)alkyl, optionally substituted aryl (especially optionally substituted phenyl), optionally substituted heteroaryl (especially optionally substituted pyridyl or pyrimidinyl), optionally substituted aryloxy (especially optionally substituted phenoxy), optionally substituted heteroaryloxy (especially optionally substituted pyridyloxy or pyrimidinyloxy), optionally substituted aryl(C1-4)- alkyl (especially optionally substituted benzyl, optionally substituted phenethyl and optionally substituted phenyl n-propyl) in which the alkyl moiety is optionally substituted with hydroxy, optionally substituted heteroaryl (C1-4)alkyl (especially optionally substituted pyridyl- or pyrimidinyl(C1~4)alkyl, optionally substituted aryl(C2~4)alkenyl (especially optionally substituted phenylethenyl), optionally substituted heteroaryl(C2~4)alkenyl (especially optionally substituted pyridylethenyl or pyrimidinylethenyl), optionally substituted aryl (C1~4)alkoxy (especially optionally substituted benzyloxy), optionally substituted heteroaryl (C1-4)- alkoxy (especially optionally substituted pyridylor pyrimidinyl(C1~4)alkoxy), optionally substituted aryloxy(C1~4)alkyl (especially phenoxymethyl), optionally substituted heteroaryloxy (C1-4) alkyl (especially optionally substituted pyridyloxy- or pyrimidinyloxy(C1~4)alkyl), acyloxy (especially acetyloxy and benzoyloxy), cyano, thiocyanato, nitro, -NR'R", -NHCOR', -NHCONR'R", -CONR'R", -COOR'.

-OSO2R', -SO2R': -COR', -CR'=NR" or -N=CR'R" in which R' and R" are independently hydrogen, C14 alkyl, C1-4 alkoxy, C14 alkylthio, C36 cycloalkyl, C36 cycloalkyl(C14)alkyl, optionally substituted aryl (especially optionally substituted phenyl) or optionally substituted aryl(C1~4)alkyl (especially optionally substituted benzyl), the phenyl and benzyl groups being optionally substituted with halogen, C1-4 alkyl or C1-4 alkoxy.

In one aspect the invention includes a compound of formula (I) wherein A, B, X, Y and Z, provided that they are not all hydrogen, are independently hydrogen, halogen, hydroxy, C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C24 alkynyl, C24 alkenyloxy, C2-4 alkynyloxy, C14 alkylcarbonyloxy, benzoyloxy, amino, mono(C1~4)alkylamino, di(C1~4)alkylamino, C14 alkylcarbonylamino, benzoylamino, nitro, cyano, -CO2R1, -CONR1R2, -COR1, -CR1=NR2 or -N=CR1R2 and R1 and R2 are independently hydrogen, C14 alkyl, cyclo (C3-6) alkyl, cyclo(C3~6)alkyl(C1~4)alkyl, phenyl, phenyl(C1~4)alkyl, phenyl(C2~4)alkenyl or phenyl(C2~4)alkynyl; the aliphatic moities of any of the foregoing being optionally substituted with halogen, hydroxy or C1-4 alkoxy and the phenyl moieties of any of the foregoing being optionally substituted with halogen, hydroxy, mercapto, C14 alkyl, C14 alkoxy, halo (C1-4) alkyl, halo (C1-4) alkoxy, C1-4 alkylthio, hydroxy (C1-4) alkyl, C1-4alkoxy (C1-4)alkyl, phenyl, phenoxy, C1-4 alkylcarbonyloxy, C1-4 alkylcarbonylamino, benzoyloxy, benzoylamino, cyano, nitro, amino, monoor di(C1-4)alkylamino, carboxy or C1-4 alkoxycarbonyl.

The invention is illustrated by the compounds listed in Table I which follows.

TABLE I

Compound Melting No. X Y Z A B point ( C) olefinic* isomer+ 1 2-F H H H H E 2 3-F H H H H E 3 4-F H H H H E 4 2-Cl H H H H E 5 3-Cl H H H H E 6 4-Cl H H H H E 7 2-Br H H H H E 8 3-Br H H H H E 9 4-Br H H H H E 10 2-I H H H H E 11 3-I H H H H E 12 4-I H H H H E 13 2-CH3 H H H H E TABLE I (Cont/d)

Compound Melting No. X Y Z A B point ( C) olefinic* isomer+ 14 3-CH3 H H H H E 15 4-CH3 H H H H E 16 2-CH3CH2 H H H H E 17 3-CH3CH2 H H H H E 18 4-CH3CH2 H H H H E 19 2-(CH3)2CH H H H H E 20 3-(CH3)2CH H H H H E 21 4-(CH3)2CH H H H H E 22 2-(CH3)3C H H H H E 23 3-(CH3)3C H H H H E 24 4-(CH3)3C H H H H E 25 2-CH3O H H H H E 26 3-CH3O H H H H Oil 7.49 E 27 4-CH3O H H H H E 28 2-CF3O H H H H E 29 3-CF3O H H H H E 30 4-CF3O H H H H E 31 2-NO2 H H H H E 32 3-NO2 H H H H E TABLE I

Compound Melting No. X Y Z Y A B point ( C) olefinic* isomer+ 33 4-NO2 H H H H E 34 2-NH2 H H H H E 35 3-NH2 H H H H E 36 4-NH2 H H H H E 37 2-HO2C H H H H E 38 3-HO2C H H H H E 39 4-HO2C H H H H E 40 2-CH3O2C H H H H E 41 3-CH3O2C H H H H E 42 4-CH3O2C H H H H E 43 2-(CN) H H H H E 44 3-(CN) H H H H E 45 4-(CN) H H H H E 46 2-HO H H H H E 47 3-HO H H H H 86-90 7.48 E 48 4-HO H H H H E 49 2-CH3C(O) H H H H E 50 3-CH3C(O) H H H H E 51 4-CH3C(O)NH H H H H E TABLE I (Cont/d)

Compund Melting No. X Y Z A B point ( C) olefinic* isomer+ 52 2-F H H H H E 53 2-F H H H H E 54 2-F H H H H E 55 2-F H H H H E 56 3-F H H H H E 57 3-F H H H H E 58 2-Cl H H H H E 59 2-Cl H H H H E 60 2-Cl H H H H E 61 3-Cl H H H H E 62 3-Cl H H H H E 63 3-Cl H H H H E 64 2-CH3 H H H H E 65 3-CH3 H H H H E 66 3-CH3O H H H H E 67 3-CH3 5-CH3 H H H E 68 3-CH3 4-CH3 H H H E 69 2-F 4-F H 4'-F H E 70 3-CH3O H H 4'-F H E TABLE I (Cont/d)

Compund Melting No. X Y Z A B point ( C) olefinic* isomer+ 71 H H H 4'-F H E 72 H H H 4'-F 6'-F E 73 2-F-C6H4 H H H H E 74 3-Cl-C6H4 H H H H E 75 4-Br-C6H4 H H H H E 76 2-I-C6H4 H H H H E 77 2-CH3-C6H4 H H H H E 78 3-(CH3)C-C6H4 H H H H E 79 4-CH3O-C6H4 H H H H E 80 2-CF30-C6H4 H H H H E 81 3-CF3-C6H4 H H H H E 82 2-C6H5O-C6H4 H H H H E 83 3-NO2-C6H4 H H H H E 84 4-NH2-C6H4 H H H H E 85 3-C6H5-C6H4 H H H H E 86 3-HO2C-C6H4 H H H H E 87 4-CH3O2C-C6H4 H H H H E 88 2-CN-C6H4 H H H H E 89 3-OH-C6H4 H H H H E TABLE I (Cont/d)

Compund Melting No. X Y Z A B point ( C) olefinic* isomer+ 90 4-CH3CONH-C6H4 H H H H E 91 2-C6H5CO2-C6H4 H H H H E 92 3-CH2:CHCH2O H H H H Gum 7.49 E 93 3-CH:CCH2O H H H H Gum 7.48&num; E * Chemical shift of singlet from olefinic proton on beta-methoxyacrylate group (ppm from tetramethylsilane).

Solvent : CDCl3 + Geometry of beta-methoxyacrylate group.

&num; lH NMR data (CDCl3) for compound 93 is as follows: 2.48 (lH,a); 3.65 (3H,s); 3.75 (3H,s); 4,60 (2H,s); 6.75-6.88 (3H,m); 7.12-7.18 (1H,t); 7.22-7.34 (3H,m); 7.40-7,44 (lH,d); 7.48 (lH,a) ppm The compounds of the invention having the general formula (I) can be prepared from substituted benzenes of general formula (IV) by the steps shown in Scheme I. Throughout Scheme I the terms A, B, X, Y and Z are as defined above, L is a halogen (iodine, bromine or chlorine) atom or a hydrogen atom, and M is a metal atom (such as a lithium atom) or a metal atom plus an associated halogen atom (such as MgI, MgBr or MgCl).

Thus compounds of general formula (I) can be prepared by treatment of ketoesters of general formula (II) with phosphoranes in a convenient solvent such as diethyl ether (see, for example, W Steglich, G Schramm, T Anke and F Oberwinkler, EP 0044448, 4.7.80).

Ketoesters of general formula (II) can be prepared by treatment of metallated species (III) with dimethyl oxalate (VI) in a suitable solvent such as diethyl ether or tetrahydrofuran. The preferred method often involves slow addition of a solution of the metallated species (III) to a stirred solution of an excess of the oxalate (VI) (see, for example, L M Weinstock, R B Currie and A V Lovell, Synthetic Communications, 1981, 11, 943, and references therein).

The metallated species (III) in which M is MgI, MgBr or MgCl (Grignard reagents) can be prepared by standard methods from the corresponding aromatic halides (IV) in which L is I, Br or C1 respectively.

With certain substituents X, Y and Z, the metallated species (III) in which M is Li can be prepared by direct lithiation of compounds (IV) in which L is H using a strong lithium base such as n-butyl-lithium or lithium di-isopropylamide (see, for example, H W Gschwend and H R Rodriguez, Orqanic Reactions, 1979, 26, 1).

Compounds of general formula (IV) can be prepared by standard methods described in the chemical literature.

Scheme I

Alternative methods for the preparation of ketoesters of general formula (II) are described in the chemical literature (see, for example, D C Atkinson, K E Godfrey, B Meek, J F Saville and M R Stillings, J. Med. Chem., 1983, 26, 1353; D Horne, J Gaudino and W J Thompson, Tetrahedron Lett., 1984, 25, 3529; and G P Axiotis, Tetrahedron Lett., 1981, 22, 1509).

Alternative approaches to the compounds of the invention of general formula (I) are outlined in Scheme II. Throughout Scheme II the terms A, B, X, Y and Z are as defined above and Q is a leaving group.

Scheme II

Compounds of general formula (I) can be prepared by treatment of phenylacetates of general formula (VII) with a base and a formic ester such as methyl formate in a suitable solvent. If the reaction is quenched with a species of general formula CH3Q wherein Q is a leaving group such as a halogen atom, compounds of general formula (I) may be obtained.

If, on the other hand, the reaction is quenched with acid, compounds of general formula (VIII) are obtained.

Compounds of general formula (VIII)

can be converted into compounds (I) by successive treatment with a base (such as potassium carbonate or sodium hydride) and a species of general formula CH3Q, wherein Q is as defined above, in a suitable solvent.

Furthermore, compounds of general formula (I) can be made from acetals of general formula (IX) under either basic or acidic conditions, in suitable solvents and at suitable temperatures. An example of a suitable base is lithium di-isopropylamide, and potassium hydrogen sulphate is an example of a suitable acidic reagent (see T Yamada, H Hagiwara and H Uda, Journal of the Chem. Soc., Chem. Commun., 1980, 838, and references therein).

Acetals of general formula (IX) may be prepared from phenylacetic esters of general formula (VII) by treatment of alkyl silyl ketene acetal derivatives of the species (VII) with trialkylorthoformates in the presence of a Lewis acid in a suitable solvent and at a suitable temperature (see, for example, K Saigo, M Osaki and T Mukaiyama, Chem. Letts., 1976, 769).

Alkyl silyl ketene acetals of derivatives of compounds of general formula (VII) can be prepared by treatment with a base and a trialkylsilyl halide of general formula R3SiCl or R3SiBr (wherein R is an alkyl group) such as trimethylsilyl chloride, or a base and a trialkylsilyl triflate of general formula R3Si-OSO2CF31 in a suitable solvent (such as dichloromethane) and at a suitable temperature (see, for example, C Ainsworth, F Chen and Y Kuo, J.

Orqanometallic Chemistry, 1972, 46, 59).

It is not always necessary to isolate the intermediates (IX); under appropriate conditions, compounds of general formula (I) may be prepared from esters of general formula (VII) in a "one pot" sequence by the successive addition of suitable reagents listed above.

Further approaches to the compounds of the invention of general formula (I) are outlined in Scheme III. Throughout Scheme III the terms A, B, X, Y, Z and Q are as defined above.

Scheme III

Thus, compounds of general formula (VIII) can be made by partial reduction of malonate derivatives (X) using a reducing agent such as lithium aluminium hydride in a suitable solvent such as diethyl ether (see, for example, M Barczai-Beke, G Dornyei, G Toth, J Tamas and Cs Szantay, Tetrahedron, 1976, 32, 1153, and references therein).

In addition, compounds of general formula (I) can be made from acrylic acid derivatives of general formula (XI) by successive treatment with bromine, a reagent of general formula CH30M, wherein M is as defined above, and sodium hydrogen sulphate or a related chemical (see, for example, G Shaw and R N Warrener, Journal of the Chemical Society, 1958, 153, and references therein).

Compounds of general formulae (VII), (X) and (XI) can be prepared by standard methods described in the chemical literature.

All the foregoing processes, either in full, or in any part (step) or parts (steps) thereof, in any combination thereof, are deemed to constitute processes according to the invention.

The compounds of the invention are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae on rice.

Puccinia recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts e.g. coffee, pears, apples, peanuts, vegetables and ornamental plants.

Erysiphe graminis (powdery mildew) on barley and wheat and other powdery mildews on various hosts such as Sphaerotheca macularis on hops,Sphaerotheca fuliqinea on cucurbits (e.g.

cucumber), Podosphaera leucotricha on apple and Uncinula necator on vines.

Helminthosporium spp., Rhynchosporium spp., Septoria spp., Pseudocercosporella herpotrichoides and Gaeumannomyces qraminis on cereals.

Cercospora arachidicola and Cercosporidium personata on peanuts and other Cercospora species on other hosts for example sugar beet, bananas, soya beans and rice.

Botrytis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts.

Alternaria species on vegetables (e.g. cucumber), oil-seed rape, apples, tomatoes and other hosts.

Venturia inaequalis (scab) on apples.

Plasmopara viticola on vines.

Other downy mildews such as Bremia lactucae on lettuce, Peronospora spp. on soya beans, tobacco, onions and other hosts and Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits.

Phytophthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts.

Thanatephorus cucumeris on rice and other Rhizoctonia species on various hosts such as wheat and barley, vegetables, cotton and turf.

Some of the compounds may show a broad range of activities against fungi in vitro. They may also have activity against various post-harvest diseases of fruit (e.g. Penicillium diqitatum and italicum and Trichoderma viride on oranges, Gloeosporium musarum on bananas and Botrytis cinerea on grapes).

Further some of the compounds may be active as seed dressings against Fusarium spp., Septoria spp., Tilletia spp., (bunt, a seed-borne disease of wheat), Ustilaqo spp. and Helminthosporium spp. on cereals, Rhizoctonia solani on cotton and Pyricularia oryzae on rice.

The compounds may move acropetally/locally in the plant tissue. Moreover, the compounds may be volatile enough to be active in the vapour phase against fungi on the plant.

The invention therefore provides a method of combating fungi, which comprises applying to a plant, to a seed of a plant, or to the locus of the plant or seed, a fungicidally effective amount of a compound as hereinbefore defined, or a composition containing the same.

The compounds may be used directly for agricultural purposes but are more conveniently formulated into compositions using a carrier or diluent. The invention thus provides a fungicidal composition comprising a compound as hereinbefore defined, and an acceptable carrier or diluent therefor.

The compounds can be applied in a number of ways. For example they can be applied, formulated or unformulated, directly to the foliage of a plant, to seeds or to other medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour or as slow release granules. Application can be to any part of the plant including the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted; or to the soil generally, to paddy water or to hydroponic culture systems. The invention compounds may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods.

The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic and eradicant treatment.

The compounds are preferably used for agricultural and horticultural purposes in the form of a composition. The type of composition used in any instance will depend upon the particular purpose envisaged.

The compositions may be in the form of dustable powders or granules comprising the active ingredient (invention compound) and a solid diluent or carrier, for example fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay. Such granules can be preformed granules suitable for application to the soil without further treatment. These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered filler.

Compositions for dressing seed may include an agent (for example a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example N-methylpyrrolidone, propylene glycol or dimethylformamide). The compositions may also be in the form of wettable powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids. The powders and granules may also contain fillers and suspending agents.

Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting or emulsifying agent and then adding the mixture to water which may also contain a wetting or emulsifying agent. Suitable organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as isophorone, cyclohexanone, and methylcyclohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.

Suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent and including a suspending agent to stop the solid settling.

Compositions to be used as sprays may be in the form of aerosols wherein the formulation is held in a container under pressure in the presence of a propellant, eg. fluorotrichloromethane or dichlorodifluoromethane.

The invention compounds can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the compounds.

Alternatively, the compounds may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.

By including suitable additives, for example additives for improving the distribution, adhesive power and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities. The invention compounds can be used as mixtures with fertilisers (eg. nitrogen-, potassium- or phosphorus-containing fertilisers).

Compositions comprising only granules of fertiliser incorporating, for example coated with, the compound are preferred. Such granules suitably contain up to 25% by weight of the compound. The invention therefore also provides a fertiliser composition comprising a fertiliser and the compound of general formula (I) or a salt or metal complex thereof.

Wettable powders, emulsifiable concentrates and suspension concentrates will normally contain surfactants eg. a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.

Suitable cat ironic agents are quaternary ammonium compounds, for example cetyltrimethylammonium bromide. Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropyl-naphthalene sulphonates).

Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonylphenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the condensation products of the said partial esters with ethylene oxide, and the lecithins. Suitable suspending agents are hydrophilic colloids (for example polyvinylpyrrolidone and sodium carboxymethylcellulose), and swelling clays such as bentonite or attapulgite.

Compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted with water before use. These concentrates should preferably be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may conveniently contain up to 95%, suitably 10-85%, for example 25-60%, by weight of the active ingredient. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0005% or 0.01% to 10% by weight of active ingredient may be used.

The compositions of this invention may contain other compounds having biological activity, eg.

compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal or insecticidal activity.

A fungicidal compound which may be present in the composition of the invention may be one which is capable of combating ear diseases of cereals (eg.

wheat) such as Septoria, Gibberella and Helminthosporium spp., seed and soil-borne diseases and downy and powdery mildews on grapes and powdery mildew and scab on apple etc. By including another funicide, the composition can have a broader spectrum of activity than the compound of general formula (I) alone. Further the other fungicide can have a synerqistic effect on the fungicidal activity of the compound of general formula (I).Examples of fungicidal compounds which may be included in the composition of the invention are carbendazim, benomyl, thiophanate-methyl, thiabendazole, fuberidazole, etridazole, dichlofluanid, cymoxanil, oxadixyl, ofurace, metalaxyl, furalaxyl, benalaxyl, fosetyl-aluminium, fenarimol, iprodione, prothiocarb, procymidone, vinclozolin, penconazole, myclobutanil, propamocarb, diniconazole, pyrazophos, ethirimol, ditalimfos, tridemorph, triforine, nuarimol, iminodi(octamethylene)diguanidine, buthiobate, propiconazole, 3-chloro-4-[4-methyl-2-(lH-1,2,4 -triazol-l-ylmethyl ) -1, 3-dioxolan-2-yl ]phenyl-4- chlorophenyl ether, prochloraz, flutriafol, hexaconazole, furconazolecis, cyproconazole, terbuconazole, pyrrolnitrin, 1-[(2RS, 4RS; 2RS, 4RS)-4-bromo-2-(2,4 -dichlorophenyl)tetrahydrofurfuryl]-1H-l,2,4-triazole 5-ethyl-5,8-dihydro-8-oxo(1,3)-dioxolo(4,5- -g)quinoline-7-carboxylic acid, (RS)-l-aminopropylphosphonic acid, 3-(2,4-dichlorophenyl)-2 (lH-1,2,4-triazol-l-yl)quinazolin-4(3H)-one, (RS)-4 (4-chlorophenyl)-2-phenyl-2-(lH-1,2,4-triazol-1-yl- methyl)butyronitrile, (+)-2-(2,4-dichlorophenyl)-3 (lH-1,2,4-triazol-1-yl)propyl 1,1,2,2, -tetrafluoroethyl ether, 4-chlorobenzyl N-(2,4 dichlorophenyl)-2-(lH-1,2,4-triazol-1- -yl)thioacetamidate, alpha-[N-(3-chloro-2,6-xylyl)-2methoxyacetamido]-qamma-butyrolactone, di-2-pyridyl disulphide l,1'-dioxide, (Z)-N-but-2-enyloxymethyl-2 -chloro-2',6'-diethylacetanilide, ethyl (Z)-N-benzyl -N-([methyl(methylthioethylideneamino -oxycarbonyl)amino]thio)-beta-alaninate, pent-4-enyl N-furfuryl-N-imidazol-l-ylcarbonyl-DL-homoalaninate, metsulfovax, fluzilazole, triadimefon, triadimenol, diclobutrazol, fenpropimorph, pyrifenox, fenpropidin, chlorozolinate, imazalil, fenfuram, carboxin, oxycarboxin, methfuroxam, dodemorph, BAS 454, blasticidin S, kasugamycin, edifenphos, iprobenfos, cycloheximide, phthalide, probenazole, isoprothiolane, tricyclazole, (RS)-4-chloro-N -(cyano(ethoxy)methyl)benzamide, pyroquilon, chlorbenzthiazone, neoasozin, polyoxin D, validamycin A, mepronil, flutolanil, pencycuron, diclomezine, phenazin oxide, nickel dimethyldithiocarbamate, techlofthalam, bitertanol, bupirimate, etaconazole, hydroxyisoxazole, streptomycin, cyprofuram, biloxazol, quinomethionate, dimethirimol, l-(2-cyano-2-methoxyiminoacetyl)-3 -ethyl urea, fenapanil, tolclofos-methyl, pyroxyfur, polyram, maneb, mancozeb, captafol, chlorothalonil, anilazine, thiram, captan, folpet, zineb, propineb, sulphur, dinocap, dichlone, chloroneb, binapacryl, nitrothal-isopropyl, dodine, dithianon, fentin hydroxide, fentin acetate, tecnazene, quintozene, dicloran, copper containing compounds such as copper oxychloride, copper sulphate and Bordeaux mixture, and organomercury compounds. The compounds of general formula (I) can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.

Suitable insecticides which may be incorporated in the composition of the invention include pirimicarb, dimethoate, demeton-s-methyl, formothion, carbaryl, isoprocarb, XMC, BPMC, carbofuran, carbosulfan, diazinon, fenthion, fenitrothion, phenthoate, chlorpyrifos, isoxathion, propaphos, monocrotophas, buprofezin, ethroproxyfen and cycloprothrin.

Plant growth regulating compounds are compounds which control weeds or seedhead formation, or selectively control the growth of less desirable plants (eg. grasses). Examples of suitable plant growth regulating compounds for use with the invention compounds are the gibberellins (eg. GA3, GA4 or GA7), the auxins (eg. indoleacetic acid, indolebutyric acid, naphthoxyacetic acid or naphthylacetic acid), the cytokinins (eg. kinetin, diphenylurea, benzimidazole, benzyladenine or benzylaminopurine), phenoxyacetic acids (eg. 2,4-D or MCPA), substituted benzoic acid (eg. triiodobenzoic acid), morphactins (eq. chlorfluoroecol), maleic hydrazide, glyphosate, glyphosine, long chain fatty alcohols and acids, dikegulac, paclobutrazol, fluoridamid, mefluidide, substituted quaternary ammonium and phosphonium compounds (eg. chloromequat chlorphonium or mepiquatchloride), ethephon, carbetamide, methyl-3,6-dichloroanisate, daminozide, asulam, abscisic acid, isopyrimol, 1-(4 -chlorophenyl)-4,6-dimethyl-2-oxo-1,2 -dihydropyridine-3-carboxylic acid, hydroxybenzonitriles (eg. bromoxynil), difenzoquat, benzoylprop-ethyl 3,6-dichloropicolinic acid, fenpentezol, inabenfide, triapenthenol and tecnazene.

The following Examples illustrate the invention.

Throughout these examples, the term "ether" refers to diethyl ether, magnesium sulphate was used to dry solutions, and reactions involving water-sensitive intermediates were performed under atmospheres of nitrogen. Unless otherwise stated, chromatography was performed using silica gel as the stationary phase. Where shown, infrared and NMR data are selective; no attempt is made to list every absorption. The following abbreviations are used throughout THF = tetrahydrofuran s = singlet DMF = N,N-dimethylformamide d = doublet GC = Gas chromatography t = triplet MS = Mass spectrum m = multiplet NMR = Nuclear Magnetic Resonance ppm = parts per mp = melting point million EXAMPLE 1 This Example illustrates the preparation of (E)methyl 2-[2-(3-methoxyphenylthio)phenyl]-3-methoxypropenoate (Compound No. 26 of Table I).

The sodium salt of 3-methoxythiophenol [prepared by treatment of 3-methoxythiophenol (2.8g) with sodium hydroxide (0.8g) in methanol (20 ml) followed by evaporation to dryness], 2-bromophenylacetic acid (4.3g) and copper(I) chloride (0.4g) in dry DMF (25 ml) were heated overnight at reflux.

The reaction mixture was cooled, poured into water and acidified with dilute hydrochloric acid.

The aqueous mixture was extracted with ether (x3) and the combined ether extracts were then extracted with dilute sodium hydroxide solution (x2). These aqueous extracts were combined and acidified with dilute hydrochloric acid and re-extracted with ether (x3). These combined ether extracts were washed with water (x 3), dried and evaporated to give an orange oil (3.5g, 96.8% by GC). The oil was treated with acidic methanol overnight at room temperature.

Normal work-up afforded methyl 2-(3-methoxyphenylthio)phenylacetate (2.9g, 91% by GC) as a yellow liquid which was used in the next stage without further purification.

1H NMR (CDC13) delta 3.64 (3H, s); 3.74 (3H, s); 3.86 (2H, s)ppm Infrared max. (film) 1739 cm 1.

To a stirred suspension of sodium hydride (0.175g, 55% dispersion in oil) in dry DMF (5 ml) at OOC was added dropwise over 5 minutes a solution of methyl 2-(3-methoxyphenylthio)phenylacetate (0.58g) and methyl formate (2.5 ml) in dry DMF (2 ml). After a further 5 minutes, the reaction mixture was allowed to warm to room temperature. After 3 hours, the reaction mixture was diluted with water, acidified with dilute hydrochloric acid and then extracted (x2) with ether. The combined ether extracts were washed with water (x3), dried and evaporated to give a yellow gum (0.65g).The gum was redissolved in dry DMF (5 ml) and potassium carbonate (0.276g) added to the solution which was cooled to OOC. A solution of dimethylsulphate (0.19 ml) in dry DMF (2 ml) was added dropwise and stirring continued at OOC for 2d hours. The reaction mixture was allowed to warm to room temperature overnight, then poured into water and extracted with ether (x3). The combined ether extracts were washed with water (x3), dried and evaporated to afford a yellow gum (0.60g).

Chromatography on silica gel (eluent ether/hexane 1:1) afforded a pure sample of the title compound (0.18g) as a colourless oil.

1H NMR (CDC13) delta 3.65 (3H, s); 3.74 (3H, s); 3.77 (3H, s); 7.49 (1H, s) ppm.

Infrared max. (film) 1711, 1634 cm 1.

EXAMPLE 2 This example illustrates the preparation of (E) -methyl 2-[2-(3-allyloxyphenylthio)phenyl]-3- -methoxypropenoate (compound No. 92 of Table I) via (E)-methyl 2-[2-(3-hydroxyphenylthio)phenyl]3-methoxypropenoate (compound No. 47 of Table I).

Methyl 2-(3-methoxyphenylthio)phenylacetate (6.08g), prepared as described in Example 1, was heated at 2000C with pyridinium hydrochloride (14.56g). After 1.75 hours, the reaction mixture was cooled to 600C and then poured into dilute hydrochloric acid. The resulting mixture was extracted with ethyl acetate (x3) and the combined organic extracts were extracted further with dilute aqueous sodium hydroxide solution (x3). These combined aqueous hydroxide extracts were acidified with dilute hydrochloric acid and re-extracted with ethyl acetate (x2). These organic extracts were combined and washed with water (x3), dried and then evaporated to give a beige solid (5.26g). The solid was redissolved in acidic methanol and allowed to stand overnight. The solvent was evaporated to give a red liquid, which was redissolved in ether and washed with aqueous sodium bicarbonate solution (xl) and water (x3). The solution was dried and evaporated to afford a red oil (5.14g) which solidified on standing. Trituration with 40-60 petroleum ether afforded methyl 2-(3 -hyroxyphenylthio)phenylacetate as a pink solid (4.6g)mp 47-50"C.

A solution of methyl 2-(3-hydroxyphenylthio)phenylacetate (4.4g) and methyl formate (19.7ml) in dry DMF (20ml) was added dropwise over 15 minutes to a stirred suspension of sodium hydride (2.lg, 55% dispersion in oil) in dry DMF (20ml) at 0-50C. After a further 15 minutes the temperature was allowed to rise to room temperature and stirred for a further 2 hours. Water and dilute hydrochloric acid were then added successively to the reaction mixture. The reaction mixture was then extracted with ether (x3) and the combined ether extracts were washed with water (x3) and dried.

Evaporation of the solvent under reduced pressure afforded a red gum (4.98g) which was redissolved in DMF (50ml) and treated with dimethylsulphate (l.llg) and potassium carbonate (1.32g). The reaction mixture was stirred at OOC for 1 hour and then left at room temperature overnight. The reaction mixture was poured into water and extracted with ether (x3).

The combined extracts were washed with water (x3) and then dried. Evaporation of the solvent under reduced pressure gave a red oil (4.20g). Trituration with dichloromethane-petroleum ether then afforded (E)methyl 2-[2-(3-hydroxyphenylthio)phenyl]-3methoxypropenoate as a solid mp 86-90"C.

Infrared max (nujol) 3325, 1697, 1618 cm 1 1H NMR (CDC13) delta 3.65 (3H,s); 3.75 (3H,s); 5.30 (lH,s); 6.65 (2H,s); 6.78-7.02 (lH,d); 7.05-7.11 (lH,t); 7.22 7.32 (3H,m); 7.40-7.45 (lH,d); 7.48 (lH,s) ppm.

Mass spectrum m/e 316 (M+) (E)-methyl 2-[2-(3-hydroxyphenylthio)phenyl]-3 -methoxypropenoate (0.474g) was treated with allyl bromide (0.242g) and potassium carbonate (0.276g) in DMF (10ml) at 21eC. After stirring for 4.75 hours and then standing at room temperature overnight, the reaction mixture was poured into water and then extracted with ether (x3). The combined organic extracts were washed with water (x3), dried and evaporated to give an orange gum (0.42g).

Chromatography on silica gel (eluent ether-hexane, 1:2) afforded the title compound (0.22g) as a pale yellow oil.

Infrared max (film) 1710, 1633 cm 1 1H NMR (CDC13) delta 3.65 (3H,s); 3.75 (3H,s); 4.44 4.46 (2H,d); 5.25-5.27 (lH,d); 5.33-5.37 (lH,d); 5.95-6.05 (lH,m); 6.71-6.74 (lH,m); 6.78 6.84 (2H,m); 7.11-7.15 (lH,t); 7.21-7.31 (3H,m); 7.38-7.40 (1H, d); 7.49 (lH,s) ppm Mass spectrum m/e 356 (M+) EXAMPLE 3 An emulsifiable concentrate is made up by mixing and stirring the ingredients until all are dissolved.

Compound No. 47 of Table I 10% Benzyl alcohol 30% Calcium dodecylbenzenesulphonate 5% Nonyl-phenolethoxylate (13 moles ethylene oxide) 10% Alkyl benzenes 45% EXAMPLE 4 The active ingredient is dissolved in methylene dichloride and the resultant liquid sprayed on to the granules of attapulgite clay. The solvent is then allowed to evaporate to produce a granular composition.

Compound No.47 of Table I 5% Attapulgite granules 95% EXAMPLE 5 A composition suitable for use as a seed dressing is prepared by grinding and mixing the three ingredients.

Compound No. 47 of Table I 50% Mineral oil 2% China clay 48% EXAMPLE 6 A dustable powder is prepared by grinding and mixing the active ingredients with talc.

Compound No. 47 of Table I 5% Talc 95% EXAMPLE 7 A suspension concentrate is prepared by ball milling the ingredients to form an aqueous suspension of the ground mixtures with water.

Compound No. 47 of Table I 40% Sodium lignosulphonate 10% Bentonite clay 1% Water 49% This formulation can be used as a spray by diluting into water or applied directly to seed.

EXAMPLE 8 A wettable powder formulation is made by mixing together and grinding the ingredients until all are thoroughly mixed.

Compound No. 47 of Table I 25% Sodium lauryl sulphate 2% Sodium lignosulphate 5% Silica 25% China clay 43% EXAMPLE 9 Compounds of the invention were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows.

The plants were grown in John Innes Potting Compost (No. 1 or 2) in 4cm diameter minipots. The test compound was formulated either by bead milling with aqueous Dispersol T or as a solution in acetone or acetone/ethanol which was diluted to the required concentration immediately before use. For the foliage diseases, the formulation (100 ppm active ingredient) was sprayed onto the foliage and applied to the roots of the plants in the soil. The sprays were applied to maximum retention and the root drenches to a final concentration equivalent to approximately 40 ppm a.i. in dry soil. Tween 20, to give a final concentration of 0.05%, was added when the sprays were applied to cereals.

The compound was applied to the soil (roots) and to the foliage (by spraying) one or two days before the plant was inoculated with the disease. An exception was the test on Erysiphe qraminis in which the plants were inoculated 24 hours before treatment.

Foliar pathogens were applied by spray as spore suspensions onto the leaves of test plants. After inoculation, the plants were put into an appropriate environment to allow infection to proceed and then incubated until the disease was ready for assessment.

The period between inoculation and assessment varied from four to fourteen days according to the disease and environment.

The disease control was recorded by the following grading 4 = no disease 3 = trace-5% of disease on untreated plants 2 = 6-25% of disease on untreated plants 1 = 26-59% of disease on untreated plants 0 = 60-100% of disease on untreated plants The results are shown in Table II.

TABLE II

COMPOUND PUCCINIA ERYSIPHE VENTURIA PYRICULARIA CERCOSPORA PLASMOPARA PHYTOPHTHORA NO. RECONDITA GRAMINIS INAEQUALIS ORYZAE ARACHIDICOLA VITICOLA INFESTANS (WHEAT) HORDEI (APPLES) (RICE) (PEANUT) (VINES) LYCOPERSICI (BARLEY) (TOMATO) 26 4 4 4 3 3 4 3 47 2 0 4 0 - - 0 92 4 2 4 2 4 4 2 93 3 2 3 3 4 4 3 - no result P34758 MJH/maa 05 April 1988 AA012

Claims

What we claim is 1. A compound of the formula (I)

and stereoisomers thereof, wherein A, B, X, Y and Z, provided that they are not all hydrogen, are independently hydrogen, halogen, hydroxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optional substituted alkynyloxy, optionally substituted acyloxy, optionally substituted amino, optionally substituted acylamino, nitro, cyano, -CO2R11 -CONR1R2, -COR1, -CR1=NR2, or -N=CR1R2 or the groups A, B, X and Z when they are in adjacent positions on the phenyl ring, may join to form a fused ring, either aromatic or aliphatic, optionally containing one or more hetereatoms;; and R1 and R2 are independently hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, optionally substituted aryl or optionally substituted aralkyl; and metal complexes thereof.
2. A compound according to claim 1 wherein A,B, X, Y and Z, provided that they are not all hydrogen, are independently hydroqen, halogen, hydroxy, C14 alkyl, C14 alkoxy, C24 alkenyl, C24 alkynyl, C24 alkenyloxy, C2-4 alkynyloxy, C1-4 alkylcarbonyloxy, benzoyloxy, amino, mono(C1-4)alkylamino, di(C1-4)alkylamino, C1-4 alkylcarbonylamino, benzoylamino, nitro, cyano, -CO2R, -CONRR, -COR, -CR=NR or -N=CRR and R1 and R2 are independently hydrogen, C1-4 alkyl, cyclo(C3-6)alkyl, cyclo(C3-6) alkyl(C1-4)alkyl, phenyl phenyl(C1-4)alkyl, phenyl(C2~4)alkenyl or phenyl(C2-4)alkynyl; the aliphatic moities of any of the foregoing being optionally substituted with halogen, hydroxy or C1-4 alkoxy and the phenyl moieties of any of the foregoing being optionally substituted with halogen, hydroxy, mercapto, C1-4 alkyl, C1-4 alkoxy, halo(C1-4)alkyl, halo(C1-4)alkoxy, C1-4 alkylthio, hydroxy(C1-4)alkyl, C1-4alkoxy(C1-4) alkyl, phenyl, phenoxy, C1-4 alkylcarbonyloxy, C1-4 alkylcarbonylamino, benzoyloxy, benzoylamino, cyano, nitro, amino, mono- or di (C1-4)alkylamino, carboxy or C14 alkoxycarbonyl.
3. Processes for preparing compounds according to claim 1 as herein described.
4. Intermediate compounds of the formulae (II) and (VII)-(XI) as herein defined.
5. A fungicidal composition comprising a fungicidally effective amount of a compound according to claim 1 and a fungicidally acceptable carrier or diluent thereof.
6. A method of combating fungi which comprises applying to plants, to the seeds of plants or to the locus of the plants or seeds, a compound according to claim 1 or a composition according to claim 5.