GB2177601A - Use of pyridine and pyridazine derivatives as fungacides - Google Patents

Abstract

The invention provides a method of combating fungus at a locus, characterised by treating the locus with a fungicidally effective amount of a compound of general formula <IMAGE> in which formula: X represents a nitrogen atom or a CH group; R represents a hydrogen atom or an optionally substituted alkyl group; or an aminocarbonyl group of general formula -CONR<2>R<3> where each of R<2> and R<3> independently represents a hydrogen atom or an optionally substituted alkyl group; or a sulphonyl group of general formula -SO2R<4> where R<4> represents an optionally substituted alkyl or aryl group; and R<1> represents a cyano group; or a group of general formula -COR<5> where R<5> is a hydrogen atom or an optionally substituted alkyl, aryl, heteroaryl, aralkyl or heteroalkyl group, or a group of general formula -NR<6>R<7>, where one of R<6> and R<7> represents a hydrogen atom and the other represents an optionally substituted alkyl, aryl, heteroaryl, aralkyl or heteroaralky group or group of formula -NH2, or R<6> and R<7> both represent a hydrogen atom or an optionally substituted alkyl group; or a group of general formula -CO2R<8> where R<8> represents a hydrogen atom or an optionally substituted alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group. The invention further relates to fungicidal compositions containing compound I as active ingredient, to certain novel compounds of general formula I, and to process for the preparation of novel compounds of formula U.

Description

SPECIFICATION Use of pyridine and pyridazine derivatives as fungicides This invention relates to the use of pyridine and pyridazine derivatives as fungicides, to fungicidally active compositions containing such derivatives, to certain novel pyridine and pyridazine derivatives per se, and to the preparation of the novel pyridine and pyridazine derivatives. More specifically, the invention relates to 1,4,5,6-tetra hydropyridine and 1 ,4,5,6-tetrahydropyridazine derivatives.

Japanese published patent application No. 51007127 (FUJISAWA), summarised in English in Derwent abstract no. 76-17640X/10, discloses a class of piperidine derivatives of general formula

wherein R, and R2 are H, mercapto, halogen, alkylthio, alkenylthio, arylthio, acylthio, formyl, hydroxyiminoalkyl, cyano, hydroxyalkyl, cyclic carbamoyl or esterified carboxyl, R3 is H or alkyl, R4 is alkyl, R5 is H or halogen, X is an acid residue, F is a double bond and m and n are 0 or 1; and when m is 1, the N atom in the piperidine ring is positively charged. The compounds are disclosed as insecticides. The only tetrahydropyridine compound disclosed is 3-cyano-1,4,5,6-tetrahydropyridine (Example 24).

DE-OLS-2257310 discloses a class of compounds of general formula

wherein Ar is a monocyclic aryl or heteroaryl group, n is from 2 to 7, and each of R and Ri represents hydrogen or lower alkyl, or salts, carbonyl or amino derivatives thereof (e.g. oximes or N-acyl derivatives). The compounds are disclosed for pharmacological use, and in particular as antiinflammatory agents.A number of tetrahydropyridine compounds are specifically disclosed, including N-phenylamino carbonyl-3-benzoyl-1 ,4,5,6-tetrahydropyridine, 3-pyridoyl-1 ,4,5,6-tetrahydropyridine, N-methyl-3-benzoyl 1,4,-5,6-tetrahydropyridine, and 3-benzoyl-1,4,5,6-tetrahydro-pyridine compounds in which the phenyl ring is unsubstituted or substituted by the following moieties: 2-, 3- or 4-chloro; 2-, 3- or 4-methyl; 2,5-, 2,3or 3,4- dimethyl; 3- or 4-trifluoromethyl; 2- or 4- methoxy; 3-ethyl; 2-hydroxy; 3,4-dimethoxy; 3- or 4fluoro; 2,6-dichloro; 3,5-di(trifluoromethyl; 2- or 4- methody; 3-ethyl; 2-hydroxy; 3,4-dimethoxy; 3- or 4fluoro; 2,6-dichloro; 3,5-di(trifluoromethyl); 4-dimethylamino; 3-chloro-4-fluoro; or 2 chloro-5-trifluoromethyl.

US patent No. 3493576 discloses a general method for the preparation of nitriles. One product specifically disclosed is 3-cyano-1,4,5,6-tetrahydropyridine. This compound is also disclosed in Chem. Ind.

(London), 1966, 52, 2169-70, J. Org. Chem, 32(3), 846-7, Chem. Pharm. Bull. (Tokyo), 1969, 17 (1), 98-104, Chem. Pharm. Bull, 1973, 21(9), 1914-26 and Japanese published patent application 70 25492, summarised in English as Chem. Abs. No. 109692. Each of these four references relates only to synthesis and no utility is disclosed for the compound.

Jnl. Lbld. Cmpd. Radiopharm, Vol. XVII, No. 2, 1919-202, discloses 3-ethoxycarbonyl- and 3-methoxycarbonyl-1,4,5,6-tetrahydropyridine. These compounds were prepared as part of a study of possible reaction pathways to isoguvacine and guvacine, which are used in studies of synaptic processes. They are not disclosed as having any utility other than as part of the study.

Helv. Chim. Acta, 1973, 56(1), 374-388 discloses the following compounds in a text describing substitution reactions of nicotinic acid derivatives. The disclosure of the compound is as starting materials in the production of iminium salts, and there is no suggestion of any further use of any of them: N-methyl-3-aminocarbonyl-1 ,4,5,6-tetrahydropyridi ne; N-methyl-3-cyano-1 ,4,5,6-tetra hyd ropyridine; N-methyl-3-methoxy-1 ,4,5,6-tetrahydropyridine; N-methyl-3-acetyl-1 ,4,5,6-tetrahydropyridine; N-benzyl-3-aminocarbonyl-1 ,4,5,6-tetrahydropyridine; N-methyl-3-(ethoxycarbonyl )methyl-l ,4,5,6-tetra hydropyridine.

J. Org. Chem, 1968, 33(2), 747-55, specifically discloses tetrahydropyridine compounds of the following formula

where R represents beta-[3-(2-methylindolyl)ethyl and R1 represents acetyl, formyl, methoxycarbonyl or tbutoxycarbonyl; or R represents methyl and R1 represents methoxycarbonyl, cyano, aminocarbonyl, (methoxycarbonyl)methyl, acetyl or (methoxycarbonyl)acetyl; or R represents hydrogen and R' represents acetyl, formyl, methoxycarbonyl, t-butoxycarbonyl or aminocarbonyl; or R1 represents acetyl and R represents methoxymethyl or -CH2OH/ or R represents beta-3(indolyl)ethyl and Ri represents (methoxycarbonyl)methyl. The compounds are disclosed as the products of hydrogenation reactions of corresponding pyridine compounds, and there is no reference to the use of the tetrahydropyridine compounds.

Chem. Ind (London) 1978, (12), 433-4 discloses 3-methoxycarbonyl- and 3-cyano-1,4,5,64etrahydropyri- dine, and N-tosyl-3-methoxycarbonyl-, N-tosyl-3-carboxyl- and N-tosyl-3-cyano-1 ,4,5,6-tetrahydropyridi ne.

The reactions of these compounds with guanidine and thiourea is discussed and no other use is proposed for them.

J. Chem. Res. Synop., 1983, 10, 245, discloses N-methyl-3-aminocarbonyl-, N-benzyl-3-aminocarbonyl-, N-benzyl-3-methoxycarbonyl-, N-benzyl-3-acetyl- and N-benzyl-3-cyano- 1 ,4,5,6-tetrahyd ropyridi ne. These compounds are disclosed as reaction products following the hydrogenation of appropriate dihydropyridine compounds and pyridinium salts, and again, it is not suggested that they have any use.

In Studi Sesser, Sez. 1, 1979, 451-60 and J. Chem. Res. Synop. 1981, (10), 306, there are disclosed the following tetrahydropyridine compounds: N-methyl-, N-benzyl- and N-phenyl-3-aminocarbonyl-1 ,4,5,6-te- trahydropyridine; N-methyl-3-acetyl-, N-benzyl-3-cyano- and N-benzyl-3-methoxycarbonyl-1 ,4,5,6,-tetrahy- dropyridine. The disclosure in both articles is of the tetrahydropyridine compounds as starting materials in reaction yielding azocines. The preparation of a number of these tetrahydropyridine compounds from corresponding 1,3-disubstituted pyridinium salts or 1,4-dihydropyridines is described in Studi Sesser, 1979, 57, 683-93. None of the articles mentions a use for the compounds other than to prepare azocines.

It has now been discovered that a class of tetrahydropyridine and tetrahydropyridazine compounds, some of which are novel compounds, has useful fungicidal activity.

According to the present invention there is provided a method of combating fungus at a locus, characterised by treating the locus with a fungicidally effective amount of a compound of general formula

in which formula: X represents a nitrogen atom or a CH group; R represents a hydrogen atom or an optionally substituted alkyl group; or an aminocarbonyl group of general formula -CONR2R3 where each of R2 and R3 independently represents a hydrogen atom or an optionally substituted alkyl group; or a sulphonyl group of general formula -SO2R4 where R4 represents an optionally substituted alkyl or aryl group; and R1 represents a cyano group; or a group of general formula -COR5 where R5 is a hydrogen atom or an optionally substituted alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group, or a group of general formula -NR5R7, where one of Re and R7 represents a hydrogen atom and the other represents an optionally substituted alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group or a group of formula -N H2, or R5 or R7 both represents a hydrogen atom or an optionally substituted alkyl group; or a group of general formula -CO2R6 where Re represents a hydrogen atom or an optionally substituted alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group.

In the above definitions, any alkyl group preferably has up to 6 carbon atoms, any aryl group present is preferably phenyl, and any heteroaryl group present is preferably pyridyl.

Optional substituents in an alkyl group may for example include for example halogen atoms and CIA alkoxy, CiA haloalkoxy, hydroxy, cyano, and amino groups. Optionally substituents in an aryl or heteroaryl group may for example include up to 3 substituents selected from halogen atoms, C,6 alkyl, haloalkyl, alkoxy, and haloalkoxy groups, and hydroxy, cyano, nitro or amino groups. Especially preferred substituents are halogen atoms, C,6 alkyl groups and the group trifluoromethyl.

Preferably R represents a hydrogen atom, an optionally substituted CiA alkyl group, an aminocarbonyl group of formula -CONR2R3 where each of R2 and R3 independently represents a hydrogen atom or CIA alkyl group, or a sulphonyl group of general formula -SO2R4 where R4 represents and CiA alkyl or a phenyl group optionally substituted by 1 or 2 C1 alkyl groups.

It is further preferred that R represents a hydrogen atom, a CIA alkyl group, an aminocarbonyl group of general formula CONR2R2 where each of R2 and R3 independently represents a hydrogen atom or a methyl group or a sulphonyl group of general formula -SO2R4 where R4 represents a methyl, or p-tolyl group. Most preferably, R is a hydrogen atom or a methyl group.

R1 advantageously represents a cyano group; or a group of general formula -COR5 where R5 is a hydrogen atom or an optionally substituted Ci4 alkyl, phenyl, pyridyl, phenyl Ci4 alkyl or pyridyl Ci4 alkyl group or a group of general formula -NR5R7 where one of R6 and R7 represents a hydrogen atom and the other represents or a C,4 alkyl or phenyl group, or a group of formula -N H2, or R6 and R7 both represent a hydrogen atom or a C,,4 alkyl group; or a group of formula -COORs where Re represents an optionally substituted C, 4 alkyl or phenyl group.It is further preferred that R' represents a cyano group; or a group of general formula -COR5 where R5 is a hydrogen atom or a methyl, ethyl or halomethylphenyl group, or a group of general formula -COORs where Rs is a methyl, ethyl or halophenyl group.

In the method according to the invention the locus preferably comprises plants subject to or subjected to fungal attack, seeds of such plants, or the medium in which the plants are growing or are to be grown.

The plants are preferably vines.

The locus may conveniently be treated with the compound I at an application rate in the range 0.1-1kg/ ha.

The invention also provides the use of a compound of formula I as defined above as a fungicide.

Further with accordance with the invention there is provided a fungicidal composition comprising an active ingredient in association with at least one carrier, preferably at least two carriers, at least one of which is a surface-active agent, characterised in that when R is a hydrogen atom, R is not a cyano, pyridoyl, benzoyl or substituted benzoyl group; and when R is a methyl or N-phenylaminocarbonyl group, Ri is not a benzoyl group.

A composition according to the invention preferably contains from 0.5 to 95% by weight of active in ingredient.

A carrier in a composition according to the invention is any material with which the active ingredient is formulated to facilitate application to the locus to be treated, which may for example be a plant, seed or soil, or to facilitate storage, transport or handling. A carrier may be a solid or a liquid, including a material which is normally gaseous but which has been compressed to form a liquid, and any of the carriers normally used in formulating fungicidal compositions may be used.

Suitable solid carriers include natural silicas such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminum silicates, for example attapulgites and vermiculites; aluminium silicates, for example kaolinites, montmorillonites and micas; calcium carbonate; calcium sulphate; synthetic hydrated silicon oxides and synthetic calcium or aluminium silicates; elements, for example carbon and sulphur; natural and synthetic resins, for example coumarone resins, polyvinyl chloride, and styrene polymers and copolymers; solid polychlorophenols; bitumen; waxes, for example beeswax, paraffin wax, and chlorinated mineral waxes; and solid fertilisers, for example superphosphates.

Suitable liquid carriers include water; alcohols, for example isopropanol and glycols; ketones, for example acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic or araliphatic hydrocarbons, for example benzene, toluene and xylene; petroleum fractions, for example kerosine and light mineral oils; chlorinated hydrocarbons, for example carbon tetrachloride, perchloroethylene and trichloroethane. Mixtures of different liquids are often suitable.

Fungicidal compositions are often formulated and transported in a concentrated form which is subsequently diluted by the user before application. The presence of small amounts of a carrier which is a surface-active agent facilitates this process of dilution.

Of particular interest in enhancing the duration of the protectant activity of the compounds of this invention is the use of a carrier which will provide a slow release of the fungicidal compounds into the environment of the plant which is to be protected. Such slow-release formulations could, for example, be inserted in the soil adjacent to the roots of a vine plant, or could include an adhesive component enabling them to be applied directly to the stem of, for example, a vine plant.

A surface-active agent may be an emulsifying agent, a dispersing agent or a wetting agent; it may be nonionic or ionic. Examples of suitable surface-active agents include the sodium or calcium salts of polyacrylic acids and lignin sulphonic acids; the condensation products of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylene oxide and/or propylene oxide; fatty acid esters or glycerol, sorbitan, sucrose or pentaerythritol; condensates of these with ethylene oxide and/or propylene oxide; condensation products of fatty alcohol or alkyl phenols, for example p-octylphenol or p-octylcresol, with ethylene oxide and/or propylene oxide; sulphates or sulphonates of these condensation products; alkali or alkaline earth metal salts, preferably sodium salts, of sulphuric or sulphonic acid esters containing at least 10 carbon atoms in the molecule, for example sodium lauryl sulphate, sodium secondary alkyl sulphates, sodium salts of sulphonated castor oil, and sodium alkylaryl sulphonates such as sodium copolymers of ethylene oxide and propylene oxide.

The compositions of the invention may for example be formulated as wettable powders, dusts, granules, solutions, emulsifiable concentrates, emulsions, suspension concentrates and aerosols. Wettable powders usually contain 25, 50 or 75%w of active ingredient and usually contain, in addition to solid inert carrier, 3-10%w of a dispersing agent and, where necessary, 0-10%w of stabiliser(s) and/or other additives such as penetrants or stickers. Dusts are usually formulated as a dust concentrate having a similar composition to that of a wettable powder but without a dispersant, and may be diluted in the field with further solid carrier to give a composition usually containing 2-10%w of active ingredient Granules are usually prepared to have a size between 10 and 100 BS mesh (1.676-0.152mm), and may be manufactured by agglomeration or impregnation techniques.

Generally, granules will contain -21-25%w active ingredient and 0-10%w of additives such as stabilisers, slow release modifiers and binding agents. Emulsifiable concentrates usually contain, in addition to a solvent and, when necessary, co-solvent, 1-50%w/v of active ingredient, 2-20%w/v emulsifiers and 020%w/v of other additives such as stabilisers, penetrants and corrosion inhibitors.Suspension concentrates are usually compounded so as to obtain a stable, non-sedimenting flowable product and usually contain 10-75%w of suspending agents such as protective colloids and thixotropic agents, 0-10%w of other additives such as defoamers, corrosion inhibitors, stabilisers, penetrants and stickers, and water or an organic liquid in which the active ingredient is substantially insoluble; certain organic solids or inorganic salts may be present dissolved in the formulation to assist in preventing sedimentation or as antifreeze agents for water.

The compositions may also contain other ingredients, for example other compounds possessing pesticidal, especially insecticidal, acaricidal, herbicidal or fungicidal, properties.

Aqueous dispersions and emulsions, for example compositions obtained by diluting a wettable powder or a concentrate according to the invention with water, also lie within the scope of the present invention.

The said emulsion may be of the water-in-oil or of the oil-in-water type, and may have a thick 'mayonaise'-like coilsistency.

Certain of the compounds of formula I are novel. Accordingly the invention also provides compounds of formula I as defined above, with the provisos that: when R is a hydrogen atom, Ri is not a cyano, aminocarbonyl or formyl group, or a methoxy-, ethoxyor t-butoxycarbonyl group, or an acetyl, pyridoyl, benzoyl or substituted benzoyl group; when R is an optionally substituted C,2 alkyl group R1 is not a benzoyl or optionally substituted acetyl group, or a methoxy- or t-butoxy-carbonyl group, or an aminocarbonyl, cyano or formyl group; and when R is a benzyl, phenyl, tosyl or phenylaminocarbonyl group Ri is not an aminocarbonyl, methoxycarbonyl, acetyl, carboxyl, cyano or benzoyl group.

The present invention also provides a process for the preparation of the novel compounds as defined by the preceding paragraph. The process is characterised in that a compound of general formula II,

where R1 and X are as defined above, subject to the provisos of the previous paragraph, is subjected to catalytic hydrogenation to form a compound of general formula I in which R is a hydrogen atom, followed, when R in the desired compound is other than hydrogen, by the reaction, in the presence of a base, of the resulting compound I with a compound of general formula R-L, L being a leaving group and R being as defined above, but not a hydrogen atom.The hydrogenation reaction may conveniently be effected by passing gaseous hydrogen through a solution of a compound of general formula II in a suitable solvent and in the presence of a catalyst, preferably at a pressure of up to 5 x 105 Pa. Preferred catalysts include examples being palladium, platinum and rhodium. Suitable solvents for the hydrogenation reaction include toluene, and alcohols, such as ethanol. The temperature of the reaction may be in the range of from -20 C to 100"C, and is preferably from 0 to 50"C. The reaction is conveniently effected at ambient temperature (20"C).

As mentioned above, the second step of the process is employed if it is desired to produce a compound which is substituted at the 1-position on the tetrahydropyridine ring. The leaving group L may, for example, be a halogen atom, preferably chlorine or bromine or a tosyl, mesyl or benzenesulphonyl group. Suitable solvents for the second step are polar aprotic solvents, including ethers, such as diethyl ether and 1,2-dimethoxyethane, furans such as tetrahydrofuran, and dimethylsulphoxide. Reaction may conveniently be effected at temperatures in the range from -70 C through ambient temperature to 100"C, and preferably from 0 to 50"C. The reaction is conveniently effected at ambient temperature (20"C).

The molar ratio of the reacting compounds is preferably in the range 5:1 to 1:5, and most preferably in the range 2:1 to 1:2. The base which is present is preferably a metal hydride, especially an alkali metal hydride such as sodium hydride. Other strong bases may be used, for example potassium hydroxide in dimethylsulphoxide or lithium diisopropylamide in tetrahydrofuran or diethyl ether. The reaction advantageously takes place in an inert atmosphere.

The present invention is of wide applicability in the protection of crop plants against fungal attack.

Typical crops which may be protected include vines, peanuts, broad beans, tomato and potato. The present invention is of particular value in the protection of vines against fungal disease, such as downy mildew, Plasmopara viticola.

The invention will be further understood from the following examples.

Example 1 Preparation of 3-acetyl- 1,45,6-tetrahydropyridine 3-Acetylpyridine (109) dissolved in ethanol (200ml) was hydrogenated at a pressure of 3 x 105Pa, in the presence of 10%w/w palladium on charcoal (1.8g) as catalyst, at ambient temperature (200C). When hydrogen uptake had ceased the catalyst was removed by filtration of the solution through a "Celite" pad (trade mark). The solvent was then removed under reduced pressure, and the residue vacuum distilled to yield 3-acetyl-1,4,5,6- tetrahydropyridine, (5g), b.p. 124-126"C/0.1 mm Hg.

Yield: 48% Analysis: Theory: 67.2%C 8.8%H 11.2%N C7H1,NO Found: 66.2%C 9.1%H 10.5%N Example 2 Preparation of ethyl-3-(l,4, 56, -tetrahydro)p yridazine carboxylate Ethyl-3-pyridazine carboxylate (1g) dissolved in ethanol (50ml) was hydrogenated at a pressure of 3 x 105 Pa, in the presence of 5%w/w palladium on charcoal (O.1g) as catalyst, at ambient temperature (20"C).

When hydrogen uptake had ceased, the solution was filtered through a "Celite" pad (trade mark), to remove the catalyst, and the solvent was then removed under reduced pressure. The residue was diluted with water and extracted with methylene chloride. The combined organic extracts were washed with water and dried (magnesium sulphate). The solvent was removed by evaporation under reduced pressure. Column chromatography on silica using 1% (v/v) methanol-chloroform mixture as eluant yielded ethyl-3-(1 ,4,5,6-tetrahydro)pyridazine carboxylate (1.0g) as an oil.

Yield: 99% Analysis: Theory: 53.1%C 7.8%H 17.7%N C7H12N2O2 Found: 53.3%C 7.9%H 17.6%N Example 3 Preparation of N-isopropyl-3-cyano- 1,4,5, 6-tetrahydropyridine 3-Cyano-1,4,5,6-tetrahydropyridine (1.0g) was stirred with sodium hydride (0.39) in dry tetrahydrofuran at ambient temperature (20"C) in a nitrogen atmosphere, for 1 hour. 2-Bromopropane (1.4g) dissolved in tetrahydrofuran (20ml) was added dropwise and the reaction was left for 18 hours. The solution was then diluted with water and extracted with diethyl ether. The combined organic extracts were washed with water and dried (magnesium sulphate), and the solvent was removed by evaporation under reduced pressure.Column chromatography on silica using methylene chloride as eluant yielded N-isopropyl-3cyano-1,4,5,6-tetra- hydropyridine (0.4g) as an oil.

Yield: 29.1% Analysis: Theory: 72.0%C 9.33%H 18.7%N C9H,4N2 Found: 72.1%C 9.3%H 18.7%N Example 4 Preparation of N-(p-toluenesulphonyl)-3-acetyl- l,4,5,6-tetrahydropyridine 3-Acetyl-1,4,5,6-tetrahydropyridine (1.25g) was stirred with sodium hydride, (0.24g) in dry tetrahydrofuran (20ml) at ambient temperature (20"C) in a nitrogen atmosphere, for one hour. p-Toluene-sulphonyl chloride (1.9g) in dry tetrahydrofuran (20ml) was added dropwise and the reaction left 18 hours. The solution was then diluted with water and extracted with ether. The combined organic extracts were washed with water and dried (magnesium sulphate).The solvent was evaporated under reduced pressure and the residual oil was separated by chromatography on silica using 5% (v/v) diethyl ether-methylene chloride as eluant. The process yielded N-(p-toluenesulphonyl)-3-acetyl- 1,4,5,6-tetrahydropyridine (1.2g)as a white solid, m.p. 97-100"C.

Yield: 44% Analysis Theory: 59.7%C 6.4%H 4.9%N C14H17NSO3 Found: 60.2%C 6.1%H 5.O%N Further compounds were prepared according to procedures similar to those described above. Data on these compounds are set out in Table 1 below.

The intermediate compounds used to prepare the final compounds are, in general, standard commercial products. Where the heterocyclic intermediates are not commercially available they may be readily prepared by known methods. For example, the pyridazine starting material used to prepare the compound of Example 2 was prepared as described in J.A.C.S. 1953, 75, 4086-7, whilst the pyridine starting materials used to prepare the compounds of Examples 15 and 16 below were prepared according to the method of F.B. Laforge, J.A.C.S. 1928, 50, 2484, whilst those used for Examples 17 to 20 were prepared from nicotinic acid using standard esterification techniques, for example reacting it with the appropriate alcohol in the presence of an acid chloride and a base, as halogen scavenger.The compounds of Examples 21 and 22 were prepared in analogous manner to that of Example 4, described in detail above. TABLE 1

Analysis % Ex.No. R R1 m.p.( )C C H N 5 H cyano oil (b.p. 140-142 C at 0.1 mm Hg) Calc. 66.6 7.46 25.9 Found 66.4 7.6 25.8 6 CH3- cyano oil Calc. 68.8 8.2 22.95 Found 68.2 8.2 21.2 7 H ethoxycarbonyl oil, (b.p. 98-100 C at 0.1 mm Hg) Calc. 61.93 8.39 9.03 Found 59.5 8.2 8.7 8 H methoxycarbonyl gum Calc. 59.6 7.9 9.9 Found 58.0 7.4 9.7 9 CH3- aminocarbonyl oil Calc. 60.0 8.6 20.0 Found 61.0 9.4 18.9 10 H -CONHNH2 oil Calc. 51.1 7.8 29.8 Found 50.3 8.9 27.4 11 H benzoyl oil Calc. 77.0 7.0 7.5 Found 77.0 7.3 7.5 12 H formyl 62-65 Calc. 64.8 8.2 12.6 Found 64.6 8.3 12.6 13 H propanoyl oil Calc. 69.0 9.4 10.1 Found 66.5 9.6 9.7 14 H 2-methyl-2-(2-pyridiyl)- oil Calc. 73.0 7.9 12.2 propanoyl Found 70.2 7.8 11.8 15 H 3-trifluoromethylbenzoyl 131-133 Calc. 61.2 4.7 5.5 Found 60.7 4.8 5.2 16 H 4-trifluoromethyl- 175-177 Calc. 61.2 4.7 5.5 benzoyl Found 60.9 4.6 5.7 17 H 2,6-dichlorophenoxy- 137-139 Calc. 53.0 4.1 5.1 carbonyl Found 53.2 4.0 5.2 TABLE 1 (continued) Analysis % Ex.No. R R1 m.p.( )C C H N 18 H 4-fluorophenoxycarbonyl 132-135 Calc. 65.1 5.5 6.3 Found 64.0 5.5 6.2 19 H (3-trifluoromethyl- oil Calc. 57.6 4.5 5.2 phenoxy)carbonyl Found 57.5 4.3 5.0 20 H 2,4-di-t-butylphenoxy- 95-100 Calc. 76.1 9.3 4.4 carbonyl 21 dimethyl- acetyl oil Calc. 61.3 8.2 14.3 aminocar- Found 58.2 8.6 12.6 bonyl 22 methylsul- acetyl 103-105 Calc. 47.3 6.4 6.9 phonyl Found 46.9 6.6 6.6 The fungicidal activity of compounds of the invention was investigated by means of the following tests.

a) Antisporulant activity against vine downy mildew (Plasmopara viticola; P. v.a) The test is a direct antisporulant one using a foliar spray. The lower surfaces of leaves of whole vine plants (cv Cabernet Sauvignon) are inoculated by spraying with an aqueous suspension containing 104 zoosporangia/ml 2 days prior to treatment with the test compound. The inoculated plants are kept for 24 hours in a hight humidity compartment, and then 24 hours at glasshouse ambient temperature and humidity. When the plants are dry, infected leaves are sprayed on their lower surfaces with a solution of active material in 1:1 water/acetone containing 0.04% "Triton X-155" (trade mark). The spraying is carried out with a moving track sprayer which delivers 620 1/ha, and the concentration of active material is calculated to given an application rate of 1kg/ha.After spraying, the plants are returned to normal glasshouse conditions for 96 hours and are then transferred to the high humidity compartment for 24 hours to induce sporulation, prior to assessment. Assessment is visual and is based on the percentage of the leaf area covered by sporulation compared with that on control leaves.

b) Translaminar activity against vine downy mildew (Plasmopara viticola; P. v. t) The test is a translaminar protectant one using a foliar spray. The upper surfaces of leaves of whole vine plants are sprayed at a dosage of 1 kilogram of active material per hectare using a track sprayer as described under (a). The lower surfaces of the leaves are then inoculated, up to 6 hours after treatment, with the test compound, by spraying with an aqueous suspension containing 105 zoosporangia/ml. The inoculated plants are kept for 24 hours in a high humidity compartment, 5 days at glasshouse ambient temperature and humidity and then returned for a further 24 hours to high humidity. Assessment is based on the percentage of the leaf area covered by sporulation compared with that on control leaves.

c) Direct protectant activity against vine downy mildew {Plasmopara vitocola; P. v.p) The test is a direct protectant one using a foliar spray. The lower surfaces of leaves of whole vine plants (cv Cabernet Sauvignon) are sprayed at a dosage of 1 kilogram of active material per hectare using a track sprayer as described under (a), and after a subsequent 24 hours under normal glasshouse conditions the lower surfaces of the leaves are inoculated by spraying with an aqueous solution containing 104 zoosporangia/ml. The inoculated plants are kept for 24 hours in a high humidity compartment, 5 days under normal glasshouse conditions and then returned for a further 24 hours to high humidity. Assessment is based on the percentage of leaf area covered by sporulation compared with that on control leaves.

d) Activity against broad bean rust (Uromyces fabae U.f) The test is a translaminar antisporulant one using foilar spray. Pots containing 1 plant per pot were inoculated by spraying an aqueous suspension, containing 5 x 104 spores/ml plus a little "Triton X-155" (Trade Mark), onto the undersurface of each leaf 20-24 hours before treatment with test compound. The inoculated plants were kept overnight in a high humidity compartment, dried at glass-house ambient temperature and then sprayed, on the leaf upper surface, at a dosage of 1 kg/ha of active material using a track sprayer as described under (a). After treatment the plants were kept at glass-house temperature and assessment made 11-14 days after treatment. Symptoms are assessed on the relative density of sporulating pustules per plant compared with that on control plants.

e) Activity against peanut leaf spot {Cercospora arachidicola; Ca) The test is a direct eradicant one using a foliar spray. The upper surfaces of the leaves of peanut plants (12-20cms high, monopots) are inoculated by spraying with an aqueous suspension containing 10e conidia/ml 4 hours prior to treatment with the test compound. The inoculated plants are kept at high humidity and then allowed to dry during the interval between inoculation and treatment by spraying at a dosage of 1kg of active material per hectare using a track sprayer as described under (a). After spraying the plants are moved to a humid compartment at 25-280C for a further period of up to 10 days. Assessment is based on a comparison between the levels of disease on the treated and control plants.

f) Activity against potato late blight (Phytophthora infestans P. i. p) The test measures the direct protectant activity of compounds applied as a foliar spray. Tomato plants, Cultivar Ailsa Craig, 1-15 cms high, in monopots are used. The whole plant is sprayed at a dosage of 1 kilogram of active material per hectare using a track sprayer as described under (a). The plant is then inoculated up to 6 hours after treatment with the test compound, by spraying with an aqueous suspension containing 5 x 103 zoosporangia/ml. The inoculated plants are kept in high humidity for 3 days.

Assessment is based on a comparison between the levels of disease on a comparison between the levels of disease on the treated and control plants.

The extent of disease control in all the above tests is expressed as a rating compared with a diluent sprayed control according to the criteria: 0 = less than 50% disease control 1 = about 50-80% disease control 2 = greater than 80% disease control Results of the above tests are given in Table 2 following: TABLE 2 Fungicidal activity Example Pva Pvt Pvp Uf Ca Pip 1 2 2 2 3 1 4 1 5 2 6 2 7 2 8 2 2 9 10 1 11 1 12 2 13 2 14 1 15 2 16 2 17 1 18 1 2 19 1 20 1 21 1 22 1

Claims (15)

1. A method of combating fungus at a locus, characterised by treating the locus with a fungicidally effective amount of a compound of general formula

in which formula: X represents a nitrogen atom or a CH group; R represents a hydrogen atom or an optionally substituted alkyl group; or an aminocarbonyl group of general formula -CONR2R3 where each of R2 and R3 independently represents a hydrogen atom or an optionally substituted alkyl group; or aisulphonyl group of general formula -SO2R4 where R4 represents an optionally substituted alkyl or aryl group; and Ri represents a cyano group; or a group of general formula -COR5 where R5 is a hydrogen atom or an optionally substituted alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group, or a group of general for mula -NR6R7, where one of R6 and R7 represents a hydrogen atom and the other represents an optionally substituted alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group or a group of formula -N H2, or R6 and R7 both represent a hydrogen atom or an optionally substituted alkyl group; or a group of general formula -CO2Rs where Rs represents a hydrogen atom or an optionally substituted alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group.

2. A method according to claim 1, wherein R represents a hydrogen atom, an optionally substituted C,4 alkyl group, an aminocarbonyl group of general formula -CONR2R3 where each of R2 and R3 independently represents a hydrogen atom or a C14 alkyl group, or a sulphonyl group of general formula -SO2R4 where R4 represents a C1.4 alkyl group or a phenyl group optionally substituted by 1 or 2 C14 alkyl groups.

3. A method according to claim 2, wherein R represents a hydrogen atom or a methyl group.

4. A method according to any one of claims 1 to 3, wherein R' represents a cyano group; or a group of general formula -COR5 where R5 is a hydrogen atom or an optionally substituted C14 alkyl, phenyl, pyridyl, phenyl C,4 alkyl or pyridyl C14 alkyl group or a group of general formula -NR6R7 where one of R6 and R7 represents a hydrogen atom and the other represents a C,4 alkyl or phenyl group, or a group of formula -NH2, or R6 and R7 both represent a hydrogen atom or a C14 alkyl group; or a group of formula -COOR6 where Re represents an optionally substituted C14 alkyl or phenyl group.

5. A method according to claim 4, wherein R1 represents a cyano group; or a group of general formula -COR5 where R5 is a hydrogen atom or a methyl, ethyl or halomethylphenyl group, or a group of general formula -COORs where R8 is a methyl, ethyl or halophenyl group.

6. A method according to any one of claims 1 to 5, in which the locus comprises plants subject to or subjected to fungal attack, seeds of such plants, or the medium in which the plants are growing or are to be grown.

7. A method according to claim 1, substantially as hereinbefore described.

8. The use of a compound of formula I as defined in any of claims 1 to 5, as a fungicide.

9. A fungicidal composition comprising an active ingredient and at least two carriers, at least one of which is a surface-active agent, characterised in that when R is a hydrogen atom, R' is not a cyano, pyridoyl group, benzoyl or substituted benzoyl group; and when R is a methyl or N-phenylaminocarbonyl group, R' is not a benzoyl group.

10. A composition according to claim 9, substantially as hereinbefore described.

11. A compound of formula I, as defined in any of claims 1 to 5 provided that when R is a hydrogen atom, Rl is not a cyano, aminocarbonyl or formyl group, or a methoxy, ethoxy-or t-butoxycarbonyl group, or an acetyl, pyridoyl, benzoyl or substituted benzoyl group; when R is an optionally substituted C,-2 alkyl group R1 is not a benzoyl or optionally substituted acetyl group, or a methoxy- or t-butoxycarbonyl group, or an aminocarbonyl, cyano or formyl group; and when R is a benzyl, phenyl, tosyl or phenylaminocarbonyl group R1 is not an aminocarbonyl, methoxycarbonyl, acetyl, carboxyl, cyano or benzoyl group.

12. A process for the preparation of a compound of general formula I, as defined in claim 11, characterised in that a compound of general formula II,

is hydrogenated to form a compound of general formula I, in which R is a hydrogen atom, followed, when R in the desired compound is other than hydrogen, by the reaction, in the presence of a base, of the resulting compound I with a compound of general formula R L being a leaving group, R being as defined in Claim 11, but not a hydrogen atom, X being as defined in Claim 11, and Ri and R being subject to the limitations of Claim 11.

13. A process according to claim 12, in which the base is a metal hydride.

14. A process according to claim 12 or 13, substantially as hereinbefore described, for the preparation of a compound of general formula I as defined in claim 11, and substantially as hereinbefore described.

15. A compound of general formula I, as defined in claim 11 when produced by a process as defined by either of claims 12 and 13.