GB2303131A - Heterocyclic fungicidal compounds - Google Patents

Abstract

Compounds of formula (I): or stereoisomers thereof, wherein R 1 is H, halo, alkyl or alkoxy, A is -CR 2 =CR 3 - in which R 2 and R 3 are either both hydrogen or, together with the carbon atoms to which they are attached, join to form an optionally substituted fused benzene ring, or -CH(R 4 )X- in which R 4 is H or OH or a derivative thereof and X is CH 2 , O, S or NR 5 where R 5 is H or alkyl, n is 1, 2 or 3 and W is CH 3 O.CH=C.CO 2 CH 3 , CH 3 O.CH=C.CONR 6 R 7 , CH 3 O.N=C.CO 2 CH 3 , or CH 3 O.N=C.CONR 6 R 7 where R 6 and R 7 are independently H or alkyl, have fungicidal activity and may be used for treating plants.

Description

FUNGICIDES The present invention relates to novel nitrogen-containing heterocyclic compounds, to processes for preparing them, to compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants.

More particularly, the invention relates to fungicidal compounds in which a nitrogen-containing heterocycle is attached through its nitrogen atom and an oxymethylene linking group to a phenyl ring containing an ortho methyl ss-methoxyacrylate group or methyl ss-methoxyiminoacetate group or an amide derivative thereof.

Fungicidal compounds in which a nitrogen-containing heterocycle is linked through an oxymethylene group to a phenyl ring containing an ortho methyl ss-methoxyacrylate group are described in, for example, EP-A-0278595 and EP-A-0350691. In these compounds the heterocycle is a C-linked heteroaromatic group, such as pyridyl or pyrimidinyl.

According to the present invention there is provided a compound having the general formula (I) or a stereoisomer thereof, wherein R1 is H, halo, alkyl or alkoxy, A is -CR2=CR3 - in which R2 and R3 are either both hydrogen or, together with the carbon atoms to which they are attached, join to form an optionally substituted fused benzene ring, or -CH(R4)X- in which R4 is H or OH or a derivative thereof and X is CH2, O, S or NR5 where R5 is H or alkyl, n is 1, 2 or 3 and W is CH30.CH=C.C02CH3, CH30.CH=C.CONR4R5, CH30.N=C.C02CH3 or CH30.N=C.CONR6R7 where R6 and R7 are independently H or alkyl.

Because the carbon-carbon double bond of the W group is unsymmetrically substituted, the compounds of the invention may be obtained in the form of mixtures of (E)- and (Z)-geometric isomers. However, these mixtures can be separated into individual isomers, and this invention embraces such isomers and mixtures thereof in all proportions. The (i)-isomers with respect to the W group are usually the more fungicidally active and form a preferred embodiment of the invention.

Further, when R1 or R4 is other than hydrogen the compounds of the invention may exist in the form of mixtures of optical isomers. However, these mixtures can be separated into the component isomers by known methods and this invention embraces such isomers and mixtures thereof in all proportions.

Halo includes fluoro, chloro, bromo and iodo.

Alkyl and the alkyl moiety of alkoxy, can be in the form of straight or branched chains and, unless otherwise stated, suitably contain from 1 to 6, preferably from 1 to 4, carbon atoms. Examples are methyl1 ethyl, iso-propyl and tert-butyl.

When R1 is alkyl or alkoxy it may be substituted by, for example, fluorine or chlorine atoms or by an alkoxy group.

Derivatives of compounds where R4 is hydroxy include ethers and esters prepared by standard methods documented in the chemical literature. Such ethers and esters include compounds where R4 is benzyloxy or benzoyloxy in which the benzene ring is optionally substituted with one or more substituents selected from the group comprising halo (eg. chloro, fluoro or bromo), C16 alkyl (eg. methyl, ethyl, g-propyl, n- or tert-butyl, n- or iso-amyl or n-hexyl), halo(C1 4)alkyl (especially halomethyl, eg.

trifluoromethyl, difluoromethyl, fluoromethyl or trichloromethyl), C14alkoxy (eg. methoxy), halo(C1 4)alkoxy (especially halomethoxy, eg.trifluoromethoxy), cyano, nitro, amino, mono- or di-(C1~4)alkylamino (eg. methyl- or dimethylamino), C1 4alkanoylamino (eg. formamido or acetylamino), carboxy, C1 4alkoxycarbonyl or C14alkylcarbonyloxy.

Examples of substituted benzyloxy and benzyloxy groups are 2- and 4-methylbenzyl, 2,4-difluorobenzyl, 3-trifluoromethylbenzyl, 4-cyanobenzyl, 3-chlorobenzoyl, 2-methylbenzoyl and 3-trifluoromethylbenzoyl.

Where A is -CR2=CR3- and R2 and R31 together with the carbon atoms to which they are attached, join to form a fused benzene ring, the fused ring may be substituted with, for example, halo (eg. fluoro, chloro or bromo), nitro or amino.

The invention, therefore1 includes a compound having the general formula (I) or a stereoisomer thereof, wherein R1 is H, halo, C1 6alkyl or 2 3 C1 4alkoxy; A is -CR2=CR3- in which R and R are either both hydrogen or, together with the carbon atoms to which they are attached, join to form a fused benzene ring which is optionally substituted with halo, nitro or amino groups or A is -CH(R4)X- in which R4 is H, OH, benzyloxy or benzoyloxy, the benzene ring of either of which being optionally substituted with one or more substituents selected from the group comprising halo, C1 6alkyl, halo(C1 4)alkyl, C1~4alkoxy, halo(C1 4)alkoxy, cyano, nitro, amino, mono- or di-(C1 4)alkylamino, C1 4alkanoylamino, carboxy, C14alkoxycarbonyl or C1-4al kylcarbonyloxy, and X is CH2, O, S or NR5 where R is H or C1 4alkyl, n is 1, 2 or 3 as defined above, especially the (i)-isomer of a compound in which W is CH30.CH=C.C02CH3, CH3).N=C.CO2CH3 or CH30.N=C.CONR6R7 where R6 and R7 are independently H or methyl.

In one aspect, the invention provides a compound of the general formula (I) or a stereoisomer thereof, wherein n is 1 or 2, A is CH2CH2, CH=CH, CH20 or CH(OH)CH2, R1 is H or methyl and W is as defined above, and especially the (E)-isomer of a compound where W is CH30.CH=C.C02CH3.

In another aspect, the invention provides the (i)-isomer of a compound of the general formula (I) wherein n is 2, R1 is H, A is CH2CH2 or CH20 and W is CH30.CH=C.CONR6R7, CH3O.N=C.CO2CH3, CH30.N=C.CoNR6R7 or, preferably, CH30.CH=C.C02CH3, wherein R6 and R7 are as defined above.

In yet another aspect, the invention provides a compound of the general formula (I) or a stereoisomer thereof, wherein n is 1, 2 or 3, R1 is H, halo, C1 6alkyl or C1 4alkoxy, A is -CH(R4)CH2- in which R4 is benzyloxy or benzoyloxy, the benzene ring of either of which being optionally substituted with one or more substituents selected from the group comprising halo, C16alkyl, halo(C14)alkyl, C1 4alkoxy, halo(C1 4)alkoxy, cyano, nitro, amino, mono- or di-(C1 4)alkylamino, C1-4 alkanoylamino, carboxy, C14 alkoxycarbonyl or;;C1-4 or C14 alkylcarbonyloxy, and W is CH3O.CH=C.CONR6R7, CH30.N=C.COCH3, CH3O.N=C.CONR6R7 or, preferably, CH30.CH=C.C02CH3, wherein R and R7 are as defined above.

Typically, n is 1, R1 is H, W is CH3O.CH=C.CO2CH3 and A is -CH(R4)CH2in which R is benzyl or benzoyloxy, the benzene ring of either of which being optionally substituted with chloro, di-chloro, fluoro, di-fluoro, methyl, trifluoromethyl, methoxy or cyano.

When W is CH30.CH=CONR6R7 or CH3O.M=CONR6R71 it is preferred always that R6 is H and R7 is methyl.

The present invention is illustrated by compounds of the general formula (I) listed in Tables 1 to 4. Throughout the Tables the W group has the (E)-configuration.

In the compounds of Table 1, W is CH3O.CH=C.CO2CH3.

TABLE 1 Compound A R1 R4 n Isomer No.

1 CH2CH2 H 2 2 CH2O H 2 3 CH2CH2 H 1 4 CH=CH H 1 5 CH(OH)CH2 H 1 R,S 6 CH2CH2 CH3 1 R,S 7 CH(R4)CH2 H C6H5C02 1 R,S 8 CH(R4)CH2 H C6H5CH20 1 R,S 9 CH(R4)CH2 H 3-Cl-C6H4C02 1 R,S 10 CH(R4)CH2 H 2-CH3-C6H4CH2O 1 R,S 11 CH(R4)CH2 H 3-CF3-C6H4C02 1 R,S 12 CH(R4)CH2 H 2-CH3-C6H4CO2 1 R,S 13 CH(R4)CH2 H 3-CF3-C6H4CH2O 1 R,S 14 CH(R4)CH2 H 2,4-diF-C6H3CH20 1 R,S 15 CH(R4)CH2 H 4-CN-C6H4CH2O 1 R,S 16 CH(R4)CH2 H 4-CH3-C6H4CH2O 1 R,S 17 )iH i| H 1 TABLE 2 Table 2 comprises 17 compounds of general formula (I) wherein W is CH30.CH=C.CONHCH3 and A, R1, R4 n and the isomer value are as shown for the correspondingly numbered compound in Table 1.

TABLE 3 Table 3 comprises 17 compounds of general formula (I) wherein W is CH30.N=C.C02CH3 and A, R4, n and the isomer value are as shown for the correspondingly numbered compound in Table 1.

TABLE 4 Table 4 comprises 17 compounds of general formula (I) wherein W is CH30.N=C.C0NHCH3 and A, R1, R4, n and the isomer value are as shown for the correspondingly numbered compound in Table 1.

TABLE 5 Table 5 shows melting points where measurable and selected proton NMR data obtained at 270MHz for certain compounds described in Tables 1 to 4.

Chemical shifts are measured at 200C in ppm from tetramethylsilane and deuterochloroform was used as solvent, unless otherwise stated. The following abbreviations are used: s = singlet m = multiplet d = doublet br = broad t = triplet ppm = parts per million Compound Melting Point Proton NMR Data (8) No. "C ppm 1(1) 59-60 1.02-1.19(2H,br m); 1.44-1.80(4H,br m); 2.30-2.43(2H,br m); 3.25-3.35(2H,br m); 3.78(3H,s); 3.80(3H,s); 4.61(2H,s); 7.09-7.15(1H,m); 7.25-7.35(2H,m); 7.45-7.50(1H,m); 7.57(1H,s).

1(3) 76-76.5 1.02-1.19(1H,br m); 1.40-1.78(5H,br m); 2.25-2.39(2H,br m); 3.19-3.30(2H,br m); 3.86(3H,s); 4.03(3H,s); 4.58(2H,s); 7.12-7.18(1H,m); 7.31-7.48(3H,m).

1(4) 88-88.5 1.02-1.19(1H,br m); 1.37-1.77(5H,m); 2.27-2.41(2H,br m); 2.90(3H,d); 3.14-3.29(2H,br m); 3.95(3H,s); 4.58(2H,s); 6.65-6.76(1H,br m); 7.12-7.19(1H,m); 7.30-7.41(2H,m); 7.42-7.49(1H,m).

Compound Melting Point Proton NMR Data (8) No. "C ppm 2(1) 131-132 2.59-2.69(2H,br m); 3.08-3.18(2H,br m); 3.49-3.61(2H,br m); 3.69(3H,s); 3.80-3.91(2H,br m); 3.81(3H,s); 4.62(2H,s); 7.10-7.17(1H,m); 7.27-7.35(2H,m); 7.43-7.49(1H,m); 7.57(1H,s).

3(1) gum 1.70-1.80(4H,br m); 2.94-3.02(4H,br m); 3.69(3H,s); 3.81(3H,s); 4.62(2H,s); 7.09-7.14(1H,m); 7.25-7.33(2H,m); 7.41-7.47(1H,m); 7.57(1H,s).

4(1) gum 3.68(3H,s); 3.80(3H,s); 3.82(4H,s); 4.65(2H,s); 5.78(2H,s); 7.10-7.15(1H,m); 7.26-7.35(2H,m); 7.41-7.46(1H,m); 7.57(1H,s).

5(1) gum 1.90-2.00(1H,m); 2.20-2.34(1H,m); 2.76-2.92(2H,m); 2.94-3.04(1H,m); 3.41-3.54(1H,m); 3.58-3.68(1H,m); 3.70(3H,s); 3.82(3H,s); 4.38-4.48(1H,m); 4.62(2H,s); 7.10-7.16(1H,m); 7.27-7.34(2H,m); 7.38-7.43(1H,m); 7.58(1H,s).

6(1) gum 1.18(3H,d); 1.25-1.41(1H,m); 1.67-1.96(4H,m); 2.67-2.79(1H,m); 2.85-2.99(1H,m); 3.21-3.31(1H,m); 3.68(3H,s); 3.81(3H,s); 4.65(2H,s); 7.10-7.16(1H,m); 7.26-7.35(2H,m); 7.45-7.50(1H,m); 7.58(1H,s).

7(1) gum 1.91-2.07(1H,br m); 2.31-2.48(1H,m); 3.07-3.28(3H,m); 3.48-3.58(1H,m); 3.69(3H,s); 3.81(3H,s); 4.64(2H,s); 5.43-5.52(1H,m); 7.10-7.17(1H,m); 7.26-7.33(2H,m); 7.39-7.48(3H,m); 7.51-7.59(1H,m); 7.58(1H,s); 7.99-8.03(2H,m).

8(1) gum 1.78-1.90(1H,m); 2.06-2.20(1H,m); 3.00-3.19(3H,m); 3.30-3.39(1H,m); 3.68(3H,s); 3.80(3H,s); 4.16-4.25(1H,m); 4.42-4.52(2H,m); 4.61(2H,s); 7.10-7.16(1H,m); 7.23-7.36(H,m); 7.40-7.46(1H,m); 7.56(1H,s).

9(1) gum 1.91-2.05(1H,br m); 2.32-3.48(1H,m); 3.06-3.29(3H,m); 3.45-3.55(1H,m); 3.69(3H,S); 3.81(3H,s); 4.64(2H,s); 5.43-5.51(1H,m); 7.10-7.17(1H,m); 7.26-7.47(4H,m); 7.52(1H,ddd); 7.58(1H,s); 7.89(1H,dt); 7.98(1H,t).

10(1) 1.79-1.90(1H,m); 2.06-2.19(1H,m); 2.32(3H,s); 2.99-3.13(3H,m); 3.31-3.39(1H,m); 3.68(3H,s); 3.79(3H,s); 4.16-4.25(1H,m); 4.39-4.50(2H,m); 4.61(2H,s); 7.09-7.20(5H,m); 7.26-7.34(3H,m); 7.40-7.46(1H,m); 7.56(1H,s).

11(1) gum 1.94-2.08(1H,m); 2.34-2.49(1H,m); 3.06-3.30(3H,m); 3.49-3.58(1H,m); 3.70(3H,s); 3.82(3H,s); 4.65(2H,s); 5.47-5.56(1H,m); 7.11-7.18(1H,m); 7.26-7.35(2H,m); 7.41-7.48(1H,m); 7.43-7.51(1H,m); 7.59(1H,s); 7.79-7.85(1H,m); 8.17-8.22(1H,m); 8.26-8.29(1H,m).

12(1) gum 1.91-2.04(1H,m); 2.30-2.47(1H,m); 2.58(3H,s); 3.07-3.26(3H,m); 3.48-3.58(1H,m); 3.69(3H,s); 3.81(3H,s); 4.63(2H,s); 5.41-5.50(1H,m); 7.10-7.17(1H,m); 7.17-7.32(4H,m); 7.35-7.40(1H,m); 7.41-7.48(1H,m); 7.59(1H,s); 7.84-7.89(1H,M).

13(1) gum 1.80-1.90(1H,m); 2.09-2.21(1H,m); 3.01-3.19(3H,m); 3.30-3.39(1H,m); 3.68(3H,s); 3.80(3H,s); 4.17-4.27(1H,br m); 4.47-4.58(2H,m); 4.62(2H,s); 7.10-7.17(1H,m); 7.26-7.34(2H,m); 7.40-7.59(5H,m); 7.56(1H,s).

14(1) gum 1.79-1.89(1H,br m); 2.09-2.21(1H,m); 3.00-3.19(3H,m); 3.30-3.39(1H,m); 3.68(3H,s); 3.80(3H,s); 4.14-4.24(1H,m); 4.41-4.52(2H,m); 4.62(2H,s); 6.74-6.90(2H,m); 7.10-7.16(1H,m); 7.26-7.39(3H,m); 7.40-7.47(1H,m); 7.57(1H,s).

15(1) gum 1.79-1.90(1H,m); 2.09-2.20(1H,m); 3.01-3.19(3H,m); 3.29-3.38(1H,m); 3.68(3H,s); 3.80(3H,s); 4.16-4.24(1H,m); 4.46-4.57(2H,m); 4.61(2H,s); 7.10-7.17(1H,m); 7.26-7.34(2H,m); 7.39-7.45(3H,m); 7.56(1H,s); 7.59-7.65(2H,d).

16(1) gum 1.77-1.89(1H,br m); 2.03-2.18(1H,m); 2.33(3H,s); 2.99-3.17(3H,m); 3.29-3.38(1H,m); 3.68(3H,s); 3.80(3H,s); 4.15-4.23(1H,br m); 4.37-4.48(2H,m); 4.60(2H,s); 7.10-7.17(3H,m); 7.18-7.23(2H,d); 7.25-7.34(2H,m); 7.40-7.46(1H,m); 7.56(1H,s).

17(1) m.p. 79-80 3.60(3H,s); 3.72(3H,s); 4.27(4H,s); 4.70(2H,s); 7.10-7.26(5H,m); 7.26-7.35(2H,m); 7.42-7.49(1H,m); 7.55(1H,s).

Compounds of formula (I) can be prepared by reacting an amine of formula (II) with a dibromo compound of formula (III) in the presence of a base (such as a tertiary amine base, for example, triethylamine) in a convenient solvent (such as an ether solvent, for example, tetrahydrofuran). The reaction is facilitated by heating. For example, where the solvent is tetrahydrofuran, the reaction mixture is heated at 60-70"C, the reflux temperature of the solvent.

The amine of formula (II) can be prepared by the method described in EP-A-0463488 (see compound 22, Scheme 5, page 10).

The dibromo compound of formula (III) is either commercially available or can be prepared by methods well documented in the chemical literature.

The compounds of formula (I) are active fungicides and may be used to control one or more of the following pathogens: Pvricularia orvzae on rice and wheat and other Pvricularia spp. on other hosts; Puccini a recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts e.g. turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants; Ervsiphe graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts such as SDhaerotheca macularis on hops, Sphaerotheca fuliainea on cucurbits (e.g. cucumber), PodosDhaera leucotricha on apple and Uncinula necator on vines; Cochliobolus spp., Helminthosporium spp., Drechslera spp. (Pvrenophora spp.), Rhynchosoorium spp., Septoria spp. (including Mvcosphaerella graminicola and Leptosphaeria nodorum), Pseudocercosporella herpotrichoides and Gaeumannomvces araminis on cereals (e.g. wheat, barley, rye), turf and other hosts; Cercospora arachidicola and Cercosporidium personatum on peanuts and other Cercospora species on other hosts, for example, sugar beet, bananas, soya beans and rice;Botrvtis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts and other Botrvtis spp. on other hosts; Alternaria spp. on vegetables (e.g. cucumber), oil-seed rape, apples, tomatoes, cereals (e.g. wheat) and other hosts; Venturia spp. (including Venturia inaeaualis (scab)) on apples, pears, stone fruit, tree nuts and other hosts; Cladosporium spp. on a range of hosts including cereals (e.g.

wheat); Monilinia spp. on stone fruit, tree nuts and other hosts; Didvmella spp. on tomatoes, turf, wheat and other hosts; Phoma spp. on oil-seed rape, turf, rice, potatoes, wheat and other hosts; Asperaillus spp. and Aureobasidium spp. on wheat, lumber and other hosts; Ascochvta spp. on peas, wheat1 barley and other hosts; Plasmopara viticola on vines; other downy mildews such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts, Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits; Pythium spp. (including Pythium ultimum) on turf and other hosts;Phvtophthora infestans on potatoes and tomatoes and other Phvtophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts; Thanatephorus cucumeris on rice and turf and other Rhizoctonia species on various hosts such as wheat and barley, vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts, oil-seed rape and other hosts; Sclerotium spp. on turf, peanuts and other hosts; Colletotrichum spp. on a range of hosts including turf, coffee and vegetables; Laetisaria fuciformis on turf; Mvcosphaerella spp. on banana, peanut, citrus, pecan, papaya and other hosts; Diaporthe spp. on citrus, soybean, melon, pear, lupin and other hosts; Elsinoe spp. on citrus, vines, olives, pecans, roses and other hosts; Pyrenopeziza spp. on oil-seed rape and other hosts;Oncobasidium theobromae on cocoa causing vascular streak dieback; Fusarium spp., Tvphula spp., Microdochium nivale, Ustilaqo spp., Urocvstis spp., Tilletia spp., and Claviceps purpurea on a variety of hosts but particularly wheat, barley, turf and maize; Ramularia spp. on sugar beet and other hosts; post-harvest diseases particularly of fruit (e.g.Pencillium digitatum and P. italicum and Trichoderma viride on oranges, Colletotrichum musae and Gloeosporium musarum on bananas and Botrvtis cinerea on grapes); other pathogens on vines, notably EutvDa lata Guignardia bidwellii, Phellinus igniarus, Phomopsis viticola, Pseudopezicula tracheiphila and Stereum hirsutum; other pathogens on lumber, notably Cephaloascus fragrant, Ceratocvstis spp., Ophiostoma piceae, Penicillium spp., Trichoderma pseudokoningii, Trichoderma viride, Trichoderma harzianum, Aspergillus niger, Leptographium lindberai and Aureobasidium pullulans; and fungal vectors of viral diseases e.g.Polvmvxa araminis on cereals as the vector of barley yellow mosaic virus (BYMV).

Further, some of the compounds may be useful as seed dressings against pathogens including Fusarium spp., Septoria spp. Tilletia spp., (e.g.

bunt, a seed-borne disease of wheat), Ustilapo spp. and Helminthosporium spp. on cereals, Rhizoctonia solani on cotton and Pvricularia orvzae on rice. In particular, some of the compounds show good eradicant activity against Plasmopara viticola and Pvthium ultimum.

The compounds may move acropetally/locally in 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 fungicidal compositions comprising a compound as hereinbefore defined and an acceptable carrier or diluent therefor. It is preferred that all compositions, both solid and liquid formulations, comprise 0.0001 to 95%, more preferably 1 to 85%, for example 1 to 25% or 25 to 60%, of a compound as hereinbefore defined.

When applied to the foliage of plants, the compounds of the invention are applied at rates of 0.1g to 10kg, preferably 1g to 8kg, more preferably 10g to 4kg, of active ingredient (invention compound) per hectare.

When used as seed dressings, the compounds of the invention are used at rates of 0.0001g (for example 0.0019 or 0.05g) to 10g, preferably 0.005g to 89, more preferably 0.005g to 49, of active ingredient (invention compound) per kilogram of seed.

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, or applied by land or aerial irrigation systems.

The term "plant" as used herein includes seedlings, bushes and trees.

Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic, systemic and eradicant treatments.

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-methylpyrrol- idone, propylene glycol or ff,N-dimethylformamide). The compositions may also be in the form of water dispersible 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.

The compositions may also be in the form of soluble powders or granules1 or in the form of solutions in polar solvents.

Soluble powders may be prepared by mixing the active ingredient with a water-soluble salt such as sodium bicarbonate, sodium carbonate, magnesium sulphate or a polysaccharide, and a wetting or dispersing agent to improve water dispersibility/solubility. The mixture may then be ground to a fine powder. Similar compositions may also be granulated to form water-soluble granules. Solutions may be prepared by dissolving the active ingredient in polar solvents such as ketones, alcohols and glycol ethers. These solutions may contain surface active agents to improve water dilution and prevent crystallisation in a spray tank.

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 cyclohexanone and methylcyclohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.

Aqueous suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent with a suspending agent included 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 of a propellant, e.g. 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 additives1 for example additives for improving the uptake, distribution, adhesive power and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities. Other additives may be included to improve the biological efficacy of the various formulations. Such additives can be surface active materials to improve the wetting and retention on surfaces treated with the formulation and also the uptake and mobility of the active material, or additionally can include oil based spray additives1 for example, certain mineral oil and natural plant oil (such as soya bean and rape seed oil) additives, or blends of them with other adjuvants.

The invention compounds can be used as mixtures with fertilisers (e.g.

nitrogen-, potassium- or phosphorus-containing fertilisers). Compositions comprising only granules of fertiliser incorporating, for example coated with, a compound of formula (I) 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.

Water dispersible powders, emulsifiable concentrates and suspension concentrates will normally contain surfactants, e.g. a wetting agent1 dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.

Suitable cationic agents are quaternary ammonium compounds, for example1 cetyltrimethylammonium bromide. Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example1 sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example, sodium dodecylbenzenesulphonate, sodium1 calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropylnaphthalene 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, alkyl glucosides, polysaccharides and the lecithins and the condensation products of the said partial esters with ethylene oxide.

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 1-85%, for example 1-25% or 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 0.0001 to 10%, for example 0.005 to 10%, by weight of active ingredient may be used.

The compositions of this invention may contain other compounds having biological activity, e.g. compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal or insecticidal activity.

By including another fungicide, the resulting composition can have a broader spectrum of activity or a greater level of intrinsic activity than the compound of general formula (I) alone. Further the other fungicide can have a synergistic 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 (RS)-1-aminopropyl- phosphonic acid, (RS)-4-(4-chlorophenyl)-2-phenyl-2-( 1H-1, 2,4-triazol-1-yl- methyl)butyronitrile, (Z)-N-but-2-enyloxymethyl-2-chloro-2',6'-diethylacetanilide, 1-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, 4-(2,2-difluoro -1,3-benzodioxol-4-yl)pyrrole-3-carbonitrile, 4-bromo-2-cyano-N,N-dimethyl- -6-trifluoromethylbenzimidazole-1-sulphonamide, 5-ethyl-5,8-dihydro-8 -oxo(1,3)-dioxol-(4,5-g)quinoline-7-carboxylic acid, a-lll-(3-chloro-2,6- -xylyl )-2-methoxyacetamido]-g-butyrolactone, H-(2-methoxy-5-pyridyl)-cyclo- propane carboxamide, alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, BAS 490F, benalaxyl, benomyl, biloxazol, binapacryl, bitertanol, blasticidin S, bromuconazole, bupirimate, butenachlor, buthiobate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, chinomethionate, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate, and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprofuram, debacarb, di-2-pyridyl disulphide 1,1'-dioxide, dichlofluanid, dichlone, diclobutrazol, diclomezine, dicloran, didecyl dimethyl ammonium chloride, diethofencarb, difenoconazole, Q,Q-di-so-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, etaconazole, ethirimol, ethoxyquin, ethyl (Z)-N-benzyl-N-([methyl(methyl-thioethylideneamino-oxycarbonyl)amino]thio)- -9-alaninate, etridiazole, fenaminosulph, fenapanil, fenarimol, fenbuconazole, fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate1 fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl, furametpyr, furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, IC1A55O4, imazalil, imibenconazole, ipconazole, iprobenfos, iprodione, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, metconazole, methfuroxam, metiram, metiram-zinc, metsulfovax, myclobutanil, NTN0301, neoasozin, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxolinic acid, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic acid, prothiocarb, pyracarbolid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinconazole, quinomethionate, quintozene, rabenazole, sodium pentachlorophenate, streptomycin, sulphur, tebuconazole, techlofthalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thifluzamide, 2-(thiocyanomethylthio)benzothiazole, thiophanatemethyl, thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triacetate salt of 1,1'-iminodi(octamethylene)diguanidine, triadimefon, triadimenol, triazbutyl, triazoxide, tricyclazole, tridemorph, triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, XRD-563, zineb and ziram.

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.

The following Examples illustrate the invention. Throughout the Examples1 the term 'ether' refers to diethyl ether, magnesium sulphate was used to dry solutions except where otherwise indicated, and solutions were concentrated under reduced pressure. All reactions were performed under an atmosphere of nitrogen and solvents were dried before use, where appropriate. Unless otherwise stated, chromatography was performed on a column of silica gel as the stationary phase.The following abbreviations are used throughout: ppm = parts per million DMF = N,N-dimethylformamide mp = melting point THF = tetrahydrofuran EXAMPLE 1 This Example illustrates the preparation of (i)-methyl 2-[2 -(piperidinooxymethyl)phenyl]-3-methoxypropenoate (Compound No.1 of Table 1) (E)-Methyl 2-[phthal imidooxymethylphenyl]-3-methoxypropenoate (5.0g: prepared as described in Preparation 4 of EP-A-0463488) was suspended in methanol (40ml) at room temperature. Hydrazine hydrate (0.689) was added and the resulting solution was stirred for 3 hours. The white precipitate which formed was filtered off and the solvent removed to give a white semi-solid. This was diluted with ether.The white solid was then filtered off and the filtrate evaporated to give (i)-methyl 2-[2-(aminooxymethyl)phenyl]-3-methoxypropenoate (2.979, 92%) as a yellow oil which was used immediately in the next stage without further purification.

A mixture of (E)-methyl 2-[2-(aminooxymethyl)phenyl]-3 methoxypropenoate (2.979), triethylamine (2.759) and dibromopentane (20ml) in THF (40ml) was heated to 700C for 3 hours. The solution was filtered and evaporated to dryness to give a yellow gum which was purified by flash column chromatography (eluted with 0.5% THF in dichloromethane and ethyl acetate) to give the title compound as a white solid (1.219, 29%).

EXAMPLE 2 This Example illustrates the preparation of (E)-methyl 2[2-(morpho -linooxymethyl)phenyl]-3-methoxypropenoate (Compound No.2 of Table 1).

The hydrochloride salt of (E)-methyl 2-[2-(aminooxymethyl)phenyl] -3-methoxypropenoate (5.09: prepared as described below), triethylamine (7.6ml) and bromoethyl ether (15ml) in THF (35ml) was refluxed for 3 hours.

The solution was filtered and the resulting filtrate evaporated to give a yellow oil. The oil was purified by flash column chromatography (eluted with 1%, 2% and 5% THF in dichloromethane) to give the title compound as a white solid (1.92g, 30%).

Preparation of the hydrochloride salt of ()-methyl 2-[2-(aminooxy methyl) phenyl] -3-methoxypropenoate.

(E)-methyl 2-[2-(phthal imidooxymethyl)phenyl]-3-methoxypropenoate (10g: prepared as described in Preparation 4 of EP-A-0463488) was suspended in methanol (1O0ml) at room temperature and hydrazine hydrate (1.7ml) added. The solvent was evaporated and toluene added. The toluene was filtered and the solid residue washed twice with toluene. The toluene solution was treated with a solution of hydrogen chloride in ethanol and then evaporated giving a yellow solid. This solid was triturated with warm ethyl acetate to give the desired hydrochloride salt as a white solid (6.29, 83%).

EXAMPLE 3 This Example illustrates the preparation of (E)-methyl 2[2-(pyrolidinooxymethyl)phenyl]-3-methoxypropenoate (Compound No.3 of Table 1).

The hydrochloride salt of ()-methyl 2-[2-(aminooxymethyl)phenyl]- -3-methoxypropenoate (5.09), triethylamine (7.6ml) and 1,4 dibromobutane (15ml) in THF (35ml) were refluxed for 3 hours. The solution was filtered and the filtrate evaporated to give a yellow oil. The oil was purified by flash column chromatography (eluted with 2% and 5% THF in dichloromethane) to give the title compound as a clear gum (2.36g, 44%).

EXAMPLE 4 This Example illustrates the preparation of ()-methyl 2[2-(piperidinooxymethyl)phenyl]-3-oximinoacetate (Compound No. 1 of Table 3).

(E)-Methyl 2-[2-phthalimidooxymethyl)phenyl]-3-oximinoacetate (5.0g: prepared as described in EP-A-0463488) was suspended in methanol (35ml) at room temperature. Hydrazine hydrate (0.689) was added and the resulting solution was stirred for 3 hours. The white precipitate which formed was filtered off and the solvent removed to give a white semi-solid. This was diluted with ether, the white solid filtered off and the filtrate evaporated to give (E)-methyl 2-[2-(aminooxymethyl )phenyl]-3-oximinoacetate (2.919, 90%) as a yellow oil which was used immediately in the next stage without further purification.

A mixture of (E)-methyl 2-[2-(aminooxymethyl)phenyl]-3-oximinoacetate (2.919), triethylamine (3.8ml), sodium iodide (0.2g) and 1,5 dibromopentane (16ml) in THF (30ml) was refluxed for 2 hours at 700C. The solution was filtered and evaporated to dryness to give a yellow oil which was purified by flash column chromatography (eluted with 0.5%, 2% and 10% THF in dichloromethane) to give the title compound as a white solid (1.669, 44%).

EXAMPLE 5 The compounds 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 4 cm diameter minipots. The test compounds were 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. The formulations (100 ppm active ingredient) were sprayed on to the foliage or 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 was added to give a final concentration of 0.05% when the sprays were applied to cereals.

For most of the tests the compounds were applied to the soil (roots) or to the foliage (by spraying) one or two days before the plant was inoculated with the disease. Exceptions were the tests on Erysiphe oraminis and Puccini a recondita in which the plants were inoculated 24 hours and 48 hours1 respectively, before treatment. Foliar pathogens were applied by spray as zoosporangial 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 level present (i.e. leaf area covered by actively sporulating disease) on each of the treated plants was recorded using the following assessment scale: O = 0% disease present 20 = 10.1-20% disease present 1 = 0.1-1% disease present 30 = 20.1-30% disease present 3 = 1.1-3% disease present 60 = 30.1-60% disease present 5 = 3.1-5% disease present 90 = 60.1-100% disease present 10 = 5.1-10% disease present Each assessment was then expressed as a percentage of the level of disease present on the untreated control plants. This calculated value is referred to as a POCO (Percentage of Control) value.An example of a typical calculation is as follows: Disease level on untreated control = 90 Disese level on treated plant = 30 POCO = disease level on treated plant x 100 = 30 x 100 = 33.3 disease level on untreated control 90 This calculated POCO value is then rounded to the nearest of the values in the 9-point assessment scale shown above. In this particular example, the POCO value would be rounded to 30. If the calculated POCO falls exactly mid-way between two of the points, it is rounded to the lower of the two values.

The results are shown in Table 6.

TABLE 6 Compound No ERYSGT LEPTNO PUCCRT PLASVI PHYTIN VENTIN (Table No) 1(1) 0 10 0 0 0 0 1(3) 90 90 90 90 90 5 1(4) 0 90 60 60 30 0 2(1) - 90 90 - 3 0 3(1) 0 10 0 - - 0 4(1) 0 30 0 - - 0 5(1) 90 90 90 - - 0 6(1) 0 60 0 - 0 0 7(1) 90 90 90 0 60 10 8(1) 0 30 0 0 - 0 9(1) 30 90 90 0 20 0 10(1) 60 30 10 0 0 0 11(1) 90 90 90 0 60 10 12(1) 10 0 1 0 60 0 13(1) 5 10 0 0 60 0 14(1) 0 0 0 0 0 0 17(1) 0 90 90 0 90 0 - No result Unless stated otherwise, data represent activity following application as a combined foliar spray and root drench treatment at 100 ppm.

Kev to Diseases ERYSGT Ervsiohe graminis tritici PLASVI Plasmopara viticola LEPTNO Septoria nodorum PHYTIN Phvtophthora infestans PUCCRT Puccinia recondita lycopersici VENTIN Venturia inaequalis CHEMICAL FORMULAE (AS IN DESCRIPTION)

Claims (4)

1. CLAIMS 1. A compound having the general formula (I):

   or a stereoisomer thereof, wherein R1 is H, halo, alkyl or alkoxy, A is -CR2=CR3- in which R2 and R3 are either both hydrogen or, together with the carbon atoms to which they are attached, join to form an optionally substituted fused benzene ring, or -CH(R4)X- in which R4 is H or OH or a derivative thereof and X is CH2, O, S or NR5 where R5 is H or alkyl, n is 1, 2 or 3 and W is CH30.CH=C.C02CH?, CH30.CH=C.CoNR6R7, CH30.N=C.C02CH3 or CH30.N=C.CONRR7, where R6 and R are independently H or alkyl.
2. 2. A process for preparing a compound according to claim 1 as herein described.
3. 3. A fungicidal composition comprising a fungicidally effective amount of a compound according to claim 1 and a fungicidally acceptable carrier or diluent therefor.
4. 4. 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 3.