GB2277089A - Fungicidal tetrahydropyrimidine derivatives - Google Patents

Abstract

Tetrahydropyrimidine derivatives of the general formula <IMAGE> or acid-addition salts thereof, in which R represents an optionally substituted phenyl group; and R<1>, R<2>, R<3> and R<4> independently represent a hydrogen atom or an optionally substituted alkyl group are useful as plant fungicides.

Description

TETRAHYDROPYRIMIDINE DERIVATIVES This invention relates to certain tetrahydropyrimidine derivatives, a process for their preparation, compositions containing such compounds and their use as fungicides.

EP-A-O 469 685 concerns fungicidal compositions which comprise a carrier and, as active ingredient, a tetrahydropyrimidine derivative of the general formula

or an acid-addition salt or metal salt complex thereof, in which n is O, 1, 2 or 3; R represents an optionally substituted alkyl1 aryl or aralkyl group; R1 represents a hydrogen atom or an optionally substituted alkyl or aralkyl group; R represents an optionally substituted aryl group; p is O or 1;X represents group -NR - or 3 3 3 -NR -NR - where each R independently represents a hydrogen atom or an optionally substituted alkyl, aryl or aralkyl group or R and (X)p-A-R together represent a group -(CR4R5) -N(A-R)- where q is p 4 5 q 2 or 3 and each of R and R is independently selected from a group consisting of hydrogen atoms and optionally substituted alkyl groups; and A represents a group -(CR6R7)m- where m is O, 1, 2, 3 6 7 or 4 and each of R and R7 is independently selected from a group consisting of hydrogen atoms and optionally substituted alkyl groups; with the provisos that (i) when p is 1, X is NH, m is O, R1 is H and n is 0 then R2 is not a naphthyl group, a phenyl group substituted at the 4-position by a cyclohexyl, C4 12 alkyl,C612 alkoxy, C4-8 alkylthio, (C6 8 alkoxy)carbonyl, 4-methylphenylthio, 4-chlorophenylthio, benzyl, phenylethyl or dibutylamino group, a phenyl group substituted at the 3-position by a hexylthio group or a phenyl group substituted at the 3- and 4-position by a -(CH2)4 group; (ii) when p is 1, Xis NH, mis O, R1is CH3 and n is 0 then R2 is not a phenyl group substituted at the 4-position by a cyclohexyl or C46 alkyl group; and (iii) when p is 1, Xis NH, mis O, R1 is H, n is 2 and R is 5,5-dimethyl then R2 is not a phenyl group substituted at the 4-position by a cyclohexyl group.

However, only three compounds (Examples 13, 16 and 33) are actually disclosed in which X represents -NR3-NR3 - and, in all three compounds, A represents -CH(CH3)-.

It has now been discovered that a specific sub-group of the compounds of formula (A) in which X represents -NR3-NR3 - and A represents -CH2- exhibit particularly good fungicidal activity, especially against the cereal disease Erysiphe graminis.

According to the present invention there is therefore provided a compound of the general formula

or an acid-addition salt thereof, in which R represents an 1 substituted phenyl group; and R 2 3 and 4 optionally substituted phenyl group; and R , R , R and R independently represent a hydrogen atom or an optionally substituted alkyl group.

When the compounds of this invention contain an alkyl substituent group, this may be linear or branched and may contain up to 12, preferably up to 6, and especially up to 4, carbon atoms.

When any of the foregoing subsituents are designated as being optionally substituted, the substituent groups which are optionally present may be any one or more of those customarily employed in the development of pesticidal compounds and/or the modification of such compounds to influence their structure/activity, persistence, penetration or other property. Specific examples of such substituents include, for example, halogen atoms, nitro, cyano, hydroxyl, cycloalkyl, alkyl-cycloalkyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxy carbonyl, carboxyl, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy and halophenoxy groups. Typically, 0-3 substituents may be present.When any of the foregoing substituents represents or contains an alkyl substituent group, this may be linear or branched and may contain up to 12, preferably up to 6, and especially up to 4, carbon atoms.

Cycloalkyl substituents may contain from 3 to 8, preferably from 3 to 6, carbon atoms.

It is preferred that R represents a phenyl group optionally substituted by one or more substituents selected from C14 alkyl, C14 haloalkyl, C1,4 alkoxyalkyl and C14 alkyl-substituted C36 cycloalkyl groups.

More preferably, R represents a phenyl group optionally substituted by one or more substituents selected from C14 alkyl and C1 4 alkyl-substituted C36 cycloalkyl groups.

R1 and R2 It is also preferred that R and R independently represent a hydrogen atom or a C14 alkyl group optionally substituted by one or more substituents selected from halogen atoms and C14 alkyl-substituted phenyl groups.

More preferably, R and R independently represent a hydrogen atom or a C14 alkyl, especially a methyl, group optionally substituted by one or more C14 alkyl-substituted phenyl groups.

Preferably, R3 and R4 independently represent a C14 alkyl, especially a methyl, group.

A particularly preferred sub-group of compounds of formula I is that in which R represents a methylphenyl, ethylphenyl, propylphenyl, butylphenyl or methylcyclohexyl-phenyl group; R1 represents a hydrogen atom, methyl or butylbenzyl group; R2 represents a hydrogen atom or a methyl group; and R and R4 both represent a methyl group.

The compounds of formula I may form acid-addition salts with a variety of acids. However, acid-addition salts with acids such as saccharin and mineral acids, particularly hydrochloric acid, are especially preferred.

It should also be appreciated that the compounds of formula I are capable of existing as different geometric isomers. The present invention thus includes both the individual isomers and mixtures of such isomers.

The present invention also provides a process for the preparation of a compound of formula I as defined above, or an acid-addition salt thereof, which comprises hydrogenating a compound of the general formula

or an acid-addition salt thereof, in which R, R,R and R4 are as defined above; R' represents a hydrogen atom; R" represents a hydrogen atom or an optionally substituted alkyl group; or R' and R" together represent a single carbon-carbon bond; and, if desired reacting the compound of formula I so obtained with an acid to form an acid-addition salt thereof.

Preferably, hydrogenation is accomplished by the use of hydrogen gas with a metal catalyst, such as palladium on charcoal.

The process is conveniently carried out in the presence of a solvent. Suitable solvents include ethers, such as dioxane, and alcohols, such as ethanol. The reaction is preferably performed in the presence of an acid. Suitable acids include dilute mineral acids such as dilute hydrochloric acid. The reaction is conveniently carried out at a temperature in the range from ambient temperature (about 15 C) to 800 C, the preferred reaction temperature being from ambient temperature to 60"C.

Compounds of formula II in which R' represents a hydrogen atom and R" represents an optionally substituted alkyl group may be conveniently prepared by reacting a compound of formula II in which R' and R" both represent a hydrogen atom with an alkylating agent, such as a dialkyl sulphate, especially dimethyl sulphate, an alkyl chloride, alkyl bromide or alkyl iodide, an alkyl methylsulphonate or an alkyl toluenesulphonate. The reaction is conveniently carried out in the presence of a solvent, such as tetrahydrofuran.

Compounds of formula II in which R' and R" both represent a hydrogen atom may be prepared by hydrogenating a compound of formula II in which R' and R" together represent a single carbon-carbon bond, for example, using hydrogen gas with a palladium on charcoal catalyst under neutral conditions.

Compounds of formula II in which R' and R" together represent a single carbon-carbon bond may be prepared by reacting a compound of the general formula

R2 R3 and R4 in which R, R and R4 are as defined above, with a compound of the general formula

in which R is as defined above.

Compounds of formula IV may be prepared by conventional techniques, for example, those described in EP 0 019 450.

Compounds of formula III and V are known compounds or can be prepared by processes analogous to known processes.

The invention further provides a fungicidal composition which comprises a carrier and, as active ingredient, a compound of formula I or an acid-addition salt thereof as defined above. A method of making such a composition is also provided which comprises bringing a compound of formula I as defined above, or an acid-addition salt thereof, into association with at least one carrier. Such a composition may contain a single compound or a mixture of several compounds of the present invention.

A composition according to the invention preferably contains from 0.5 to 95% by weight of active 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 and synthetic clays and silicates, for example natural silicas such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminium silicates, for example attapulgites and vermiculites; aluminium silicates, for example kaolinites, montmorillonites and micas; calcium carbonate; calcium sulphate; ammonium 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. Thus preferably at least one carrier in a composition according to the invention is a surface-active agent. For example the composition may contain at least two carriers, at least one of which is a surface-active agent.

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 of glycerol, sorbitol, 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 dodecylbenzene sulphonate; and polymers of ethylene oxide and 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 h-10% w of active ingredient.Granules are usually prepared to have a size between 10 and 100 BS mesh (1.676 - 0.152 mm), and may be manufactured by agglomeration or impregnation techniques.

Generally, granules will contain h-75% w active ingredient and 0-10% w of additives such as stabilisers, surfactants, slow release modifiers and binding agents. The so-called "dry flowable powders" consist of relatively small granules having a relatively high concentration of active ingredient. Emulsifiable concentrates usually contain, in addition to a solvent and, when necessary, co-solvent, 1-50% w/v active ingredient, 2-20% w/v emulsifiers and 0-208 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 active ingredient, 0.5-158 w of dispersing agents, 0.1-10% 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 anti-freeze agents for water.

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 invention. The said emulsions may be of the water-in-oil or of the oil-in-water type, and may have a thick 'mayonnaise' like consistency.

The composition of the invention may also contain other ingredients, for example other compounds possessing herbicidal, insecticidal or fungicidal properties.

Of particular interest in enhancing the duration of the protective 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 a vine plant.

The invention still further provides the use as a fungicide of a compound of the general formula I as defined above or an acid-addition salt thereof or a composition as defined above, and a method for combating fungus at a locus, which comprises treating the locus, which may be for example plants subject to or subjected to fungal attack, seeds of such plants or the medium in which such plants are growing or are to be grown, with such a compound or composition.

The present invention is of wide applicability in the protection of crop plants against fungal attack. Typical crops which may be protected include potatoes, grain crops such as wheat and barley, rice, tomatoes, broad beans and apples. The duration of protection is normally dependent on the individual compound selected, and also a variety of external factors, such as climate, whose impact is normally mitigated by the use of a suitable formulation.

The invention is further illustrated by the following examples.

Example 1 Preparation of cis-4.6-dimethyl-2- [2-(4-tert-butylbenzyl)- hydrazino]-3.4,5,6-tetrahydropyrimidine hydrochloride (R-4-tert-butylphenyl; R-R-H: R -R4-CH3) (i) Preparation of 4,6-dimethyl-2-(4-tert-butylbenzylidene- hydrazino)pyrimidine A mixture of 4,6-dimethyl-2-hydrazinopyrimidine (2.6 g, 18.8 mmol), 4-tert-butylbenzaldehyde (3.5 g, 21.6 mmol) and paratoluenesulphonic acid (20 mg) in toluene (50 ml) was refluxed under Dean and Stark conditions for 2 hours. The mixture was then concentrated in vacuo. Addition of petroleum ether (boiling range 40-60"C) caused precipitation of 4,6-dimethyl-2-(4-tert-butyl benzylidene-hydrazino)pyrimidine which was isolated by filtration (3.5 g), m.pt. 157 C.

(ii) Preparation of cis-4,6-dimethyl-2-[2-(4-tert-butylbenzol)- hydrazino 1-3.4,5, 6-tetrahydropyrimidine hydrochloride A mixture of the 4, 6-dimethyl-2 - (4-tert-butylbenzylidene hydrazino)pyrimidine (1.1 g, 3.9 mmol) obtained in (i) above, palladium on charcoal lOw/w% (0.3 g) and 1N hydrochloric acid (9 ml) in ethanol (25 ml) was hydrogenated in a Parr apparatus (50 C, 414 kPa) until hydrogen uptake ceased. Filtration and evaporation of the solvent resulted in a greenish solid (1.21 g) which was purified by flash chromatography using 5:1 dichloromethane:methanol as eluant.The product-containing fractions were evaporated in vacuo to yield cis-4,6-dimethyl-2-[2-(4-tert-butylbenzyl)- hydrazino]-3,4,5,6-tetrahydropyrimidine hydrochloride (0.75 g) as a colourless solid, m.pt. 175-177"C.

Example 2 Preparation of cis-4,6-dimethyl-2-[2-(4-tert-butYlbenzyl)-2-methyl- hydrazinol-3,4,5,6-tetrahydropyrimidine hydrochloride (R-4-tert-butylphenyl; R1-R3-R4 CH; R2=H) (i) Preparation of 4,6-dimethyl-2-(2- (4-tert-butylbenzyl) - hydrazino ) pyrimidine A mixture of the 4,6-dimethyl-2-(4-tert-butylbenzylidene hydrazino)pyrimidine (12.1 g, 42.8 mmol) obtained in Example 1 (i) above and palladium on charcoal 10% (2.5 g) in ethanol (250 ml) was hydrogenated in a Parr apparatus (500 C, 500 kPa) until hydrogen uptake ceased. The crude product, which was obtained after filtration and evaporation of the solvent, was purified by flash chromatography using 7:1 toluene: ethanol as eluant.Evaporation of the product-containing fractions gave 4,6-dimethyl-2-[2-(4-tertbutylbenzyl)hydrazino]pyrimidine (8.02 g) as a colourless solid, m.pt. 91-93"C.

(ii) Preparation of 4,6-dimethyl-2- [2-(4-tert-butylbenzyl)- 2-methylhydrazinolpyrimidine Dimethyl sulphate (0.63 g, 5.0 mmol) was added to the 4,6-dimethyl-2-[2-(4-tert-butylbenzyl)hydrazino] pyrimidine (1.4 g, 4.9 mmol) obtained in (i) above in tetrahydrofuran (20 ml) and the mixture was stirred at room temperature for 3 days. The tetrahydrofuran was then distilled off in vacuo and the residue was dissolved in dichloromethane and extracted twice with aqueous sodium carbonate. Drying and evaporation of the organic phase followed by evaporation of the solvent gave a semi-crystalline mass which was purified by flash chromatography using 7:1 toluene:ethanol as eluant.Evaporation of the product-containing fractions gave 4,6-dimethyl-2-[2-(4-tert-butylbenzyl)-2-methyl- hydrazino]pyrimidine (0.9 g) as pale yellow needles, m.pt. 68-73"C.

(iii)Preparation of 4,6-dimethyl-2-[2- (4-tert-butylbenzyl )-2- methylhydrazinol-3,4,5,6-tetrahydroPyrimidine hydrochloride A mixture of the 4,6-dimethyl-2-[2-(4-tert-butylbenzyl)-2methylhydrazinojpyrimidine (2.0 g, 6.7 mmol) obtained in (ii) above, palladium on charcoal 10w/w% (0.5 g) and 15% w/w ethanolic hydrochloric acid (2.0 g) in ethanol (30 ml) was hydrogenated in a Parr apparatus (20"C/414 kPa) until hydrogen uptake ceased. The solvent was then distilled off in vacuo and the resulting residue was purified by flash chromatography using 1:1 toluene:ethanol as eluant to give 4,6-dimethyl-2-[2-(4-tert-butylbenzyl)-2-methyl- hydrazino]-3,4,5,6-tetrahydropyrimidine hydrochloride as a colourless foam.The structure of the product was confirmed by H-NMR spectroscopy using dimethylsulphoxide as solvent.

# (ppm)= 8.70(s,lH); 7.90(br.s, 1H); 7.38(br.s,lH); 7.34(dd,4H), 3.87(d,lH); 3.60(d,lH); 3.25(m,2H); 2.60(s,3H); 1.80(m,1H); 1.18(s,9H); 1.0(d,6H); 0.35(m,lH) Examples 3 to 8 By processes similar to those described in Examples 1 and 2 above, further compounds according to the invention were prepared as detailed in Table I below. In this table, the compounds are identified by reference to formula I. Melting point and 1H-NMR spectroscopy data for the compounds of Examples 3 to 8 are given in Table IA below.

Table I Example No. R R1 R2 R3 R4 3(HC1 salt) 4-C(CH3)3 Phenyl -H -CH3 -CH3 -CH3 4(HC1 salt) 4-CH(CH3)2 Phenyl " -H " 5(HC1 salt) 4-(1-CH3 cyclo- " " " " hexyl) Phenyl 6(HC1 salt) 4-CH3 Phenyl " " " " 7(HC1 salt) 4-C2H5 Phenyl n 8(HC1 salt) 4-C(CH3)3 Phenyl 4-C(CH3)3 fl I' benzyl Table IA Example M.pt. 1H-NMR (Dimethylsulphoxide as solvent) No. ( C) & (ppm) 3 7.60(br.s,2H); 7.43(dd,4H); 4.00(s,2H); 3.50(m,2H); 3.37(s,3H); 2.16(m,1H); 1.40(s,9H); 1.24(d,6H); 1.03(dd,1H) 4 105-111 5 8.24(br.s,1H); 7.62(br.s,2H); 7.33(m,4H); 5.57(m,1H); 3.80(m,2H); 3.34(m,2H); 2.14(m,1H); 1.30-1.60(m,10H); 1.13(d,6H); 1.10(s,3H); 0.85(dd,1H) 6 128-139 7 8.63(br.s,lH); 7.78(br.s,2H), 7.32(d,2H); 7.17(d,2H); 5.64(m,1H); 3.78(d,2H); 3.35(m,2H); 2.58(m,2H); 1.90(m,1H); 1.17(t,3H); l.l0(d,6H); 0.84(dd,lH) 8 219-226 Example 9 The fungicidal activity of compounds of the invention was investigated by means of the following tests.

(a) Activity against tomato early blight (Alternaria solani; AS) The test is a direct prophylactic one using a foliar spray.

Tomato seedlings (cv Outdoor Girl), at the stage at which the second leaf is expanded, are sprayed with a solution of the test compound in 1:1 water/acetone containing 0.04% "TWEEN 20" (Trade mark: a polyoxyethylene sorbitan ester surfactant). Plants are sprayed using a track sprayer equipped with 2 air-atomising nozzles. The concentration of the compound is 600 ppm and the spray volume is 750 1/ha. After drying, the plants are kept for 24 hours in a glasshouse at 20 C and 40% relative humidity followed by inoculation of the leaf upper surfaces with an aqueous suspension of A. solani conidia containing 1 x 10 conidia/ml. After 4 days in a high humidity cabinet at 21"C, disease is assessed based on the percentage of leaf surface area covered by lesions when compared with control plants.

(b) Direct protectant activity against tomato late blight (Phvtophthora infestans; PIP) The test is a direct protectant one using a foliar spray.

Tomato plants with two expanded leaves (cv. First in the Field) are sprayed with the test compound at a dosage of 600 ppm as described under (a). After drying, the plants are kept for 24 hours in a glasshouse at 20"C and 40% relative humidity. The upper surfaces of the leaves are then inoculated with an aqueous suspension containing 2 x 10 zoosporangia/ml. The inoculated plants are kept for 24 hours at 18"C in a high humidity cabinet and then for 5 days in a growth chamber at 15"C and 80% relative humidity with 14 hours light/day. The assessment is based on the percentage of diseased leaf area compared with that on control leaves.

(c) Direct protectant activity against broad bean grey mould (Botrytis cinerea; BCB) The test is a direct protectant one using a foliar spray.

Broad bean plants (cv The Sutton) with two leaf pairs are sprayed with the test compound at a dosage of 600 ppm as described under (a). After drying, the plants are kept for 24 hours in a glasshouse at 20"C and 40% relative humidity. The upper surface of the leaves are then inoculated with an aqueous suspension containing 1 x 106 conidia/ml. Plants are kept for 4 days at 22"C in a high humidity cabinet. The assessment is based on the percentage of diseased leaf area compared with that on control leaves.

(d) Direct protectant activity against barley powdery mildew (Erysiphe graminis f.sp. hordei: EGP) The test is a direct protectant one using a foliar spray.

Leaves of barley seedlings (cv. Golden Promise) at the single leaf stage are sprayed with the test compound at a dosage of 600 ppm as described under (a). After drying, the plants are kept for 24 hours in a glasshouse at 18"C and 40% relative humidity. The plants are then inoculated by dusting with mildew conidia and kept for 7 days in the glasshouse at 18"C and 40% relative humidity.

Assessment is based on the percentage of leaf area covered by sporulation compared with that on leaves of control plants.

(e) Activity against barley powder mildew (Erysiphe graminis f.sp.

hordei: EG) The test is a direct therapeutic one using a foliar spray.

Leaves of barley seedlings (cv Golden Promise) at the single leaf stage are inoculated by dusting with mildew conidia and kept in the glasshouse at 18"C and 40 relative humidity for 24 hours. Plants are then sprayed with the test compound at a dosage of 600 ppm as described under (a). After drying, plants are returned to the glasshouse at 18"C and 40% relative humidity for up to 7 days.

Assessment is based on the percentage of leaf area covered by sporulation compared with that on leaves of control plants.

(f) Activity against wheat eyespot in-vitro (Pseudocercosporella herpotrichoides; PHI) This test measures the in vitro activity of compounds gainst the fungus causing wheat eyespot. The test compound is dissolved or suspended in acetone and is added into 4 ml aliquots of half strength Potato Dextrose Broth dispensed in 25-compartment petri dishes to give a final concentration of 10 ppm test compound and 0.8258 acetone. The fungal inoculum consists of mycelial fragments of P. herpotrichoides grown in half strength Potato Dextrose Broth in shaken flasks and added to the broth to provide 5 x 104 mycelial fragments/ml broth. Petri dishes are incubated at 20"C for 10 days until the assessment of mycelial growth.

(g) Activity against Rhizoctonia in-vitro (Rhizoctonia solani: RSI) The test measures the in-vitro activity of compounds against Rhizoctonia solani that causes stem and root rots. The test compound is dissolved or suspended in acetone and added into 4ml aliquots of half strength Potato Dextrose Broth dispensed in 25-compartment petri dishes to give a final concentration of 10 ppm compound and 0.825% acetone. The fungal inoculum consists of mycelial fragments of R. solani grown in half strength Potato Dextrose Broth in shaken culture flasks and added to the broth to 4 provide 5 x 10 fragments/ml broth. Petri dishes are incubated at 20"C for 10 days until the assessment of mycelial growth.

(h) Activity against apple scab in-vitro (Venturia inaequalis; VII) This test measures the in-vitro activity of compounds against Venturia inaequalis that causes apple scab. The test compound is dissolved or suspended in acetone and added into 4ml aliquots of half strength Potato Dextrose Broth dispensed in 25-compartment petri dishes to give a final concentration of lOppm compound and 0.825% acetone. The fungal inoculum consists of mycelial fragments and spores of V. inaequalis grown on malt agar and added to the broth to provide 5 x 104 propagules/ml broth. Petri dishes are incubated at 200C for 10 days until the assessment of mycelial growth.

The extent of disease control in all the above tests is expressed as a rating compared with either an untreated control or a diluent-sprayed-control, according to the criteria: O - less than 50% disease control 1 - 50-80% disease control 2 - greater than 80% disease control The results of these tests are set out in Table II below: Table II Example Fungicidal Activity No. AS PIP BCB EGP EGT PHI RSI VII 1 2 2 2 2* 1* 2 * 2 2 1 3 2 4 1 2 1 5 2 2 1 2 2 2 2 6 2 1 1 7 1 8 2 2 2 2 2 2 * signifies concentration of test compound - 30 ppm

Claims (14)

1. CLAIMS 1. A compound of the general formula

   or an acid-addition salt thereof, in which R represents an optionally substituted phenyl group; and R, R, R and R4 independently represent a hydrogen atom or an optionally substituted alkyl group.
2. 2. A compound according to claim 1 in which R represents a phenyl group optionally substituted by one or more substituents selected from C14 alkyl, C14 haloalkyl, C1-4 alkoxyalkyl and C14 alkyl-substituted C36 cycloalkyl groups.
3. 3. A compound according to claim 1 or claim 2 in which R1 and R2 independently represent a hydrogen atom or a C14 alkyl group optionally substituted by one or more substituents selected from halogen atoms and C14 alkyl-substituted phenyl groups.
4. 4. A compound according to any one of the preceding claims in which R3 and R4 independently represent a C14 alkyl group.
5. 5. A compound according to any one of the preceding claims in which R represents a methylphenyl, ethylphenyl, propylphenyl, butylphenyl or methylcyclohexyl-phenyl group; R represents a hydrogen atom, methyl or butylbenzyl group; R represents a hydrogen atom or a methyl group; and R and R4 both represent a methyl group.
6. 6. A compound according to claim 1 as named in any one of Examples 1 to 8.
7. 7. A process for the preparation of a compound of formula I as defined in any one of the preceding claims or an acid-addition salt thereof which comprises hydrogenating a compound of the general formula

   or an acid-addition salt thereof, in which R, R, R and R4 are as defined in any one of the preceding claims; R' represents a hydrogen atom; R" represents a hydrogen atom or an optionally substituted alkyl group; or R' and R" together represent a single carbon-carbon bond; and, if desired, reacting the compound of formula I so obtained with an acid to form an acid-addition salt thereof.
8. 8. A process according to claim 7 substantially as hereinbefore described and with reference to Example 1 or Example 2.
9. 9. A compound of formula I whenever prepared by a process according to claim 7 or claim 8.
10. 10. A fungicidal composition which comprises a carrier and, as active ingredient, a compound of formula I or an acid-addition salt thereof as defined in any one of claims 1 to 6 or 9.
11. 11. A composition according to claim 10 which comprises at least two carriers, at least one of which is a surface-active agent.
12. 12. A method of combating fungus at a locus which comprises treating the locus with a compound of formula I or an acid-addition salt thereof as defined in any one of claims 1 to 6 or 9 or with a composition as defined in claim 10 or claim 11.
13. 13. A method according to claim 12 in which the locus comprises plants subject to or subjected to fungal attack, seeds of such plants or the medium in which such plants are growing or are to be grown.
14. 14. The use as a fungicide of a compound of formula I or an acid-addition salt thereof as defined in any one of claims 1 to 6 or 9 or with a composition as defined in claim 10 or claim 11.