AU647416B2

AU647416B2 - Guanidines as fungicides

Info

Publication number: AU647416B2
Application number: AU65075/90A
Authority: AU
Inventors: Michel Jean Jung; John Walter Liebeshuetz; Thomas Alexander Kendrick Smith
Original assignee: Dow Chemical Co Ltd; Dow Chemical Co
Current assignee: Dow Chemical Co Ltd
Priority date: 1989-10-10
Filing date: 1990-10-09
Publication date: 1994-03-24
Anticipated expiration: 2010-10-09
Also published as: WO1991005473A1; AU6507590A; NZ235608A; BR9007740A; JPH05504946A; GB8922750D0; CA2066164A1; EP0593438A1

Description

WO 91/05473 PCT/GB90/01555 -1- FUNGICIDAL COMPOSITIONS, FUNGICIDAL COMPOUNDS, THEIR PRODUCTION AND USE This invention relates to novel chemical compounds having fungicidal activity, and in particular to such compounds containing a guanidine group and to the use of these and other compounds as fungicides.

Certain substituted guanidines are disclosed without reference to antifungal activity in an article by Glushkov and Nikolaeva (Chem Abst. Vol 110, No. 212684r) and in Dutch Patent No. 6510117.

Many substituted guanidines are known to have antifungal and antibacterial activity. A detailed review of the antifungal activity of such compounds is to be found in International Pest Control, November/December 1986, p.p.148-155 Hudson, I.A.O. Ojo, and M. Pianka).

Fungicidally active compounds containing a guanidinetype grouping compounds are also disclosed, for example in U.S. Patent No. 2988478.

The present invntion provides the use as a fungicide of compounds of the formula

R

1

I

/N C R3R(CRR 5 pR 6

R

7

R

1

\I-C

N NCR3R CR5R5)p-R6

N

R

OR

R

1 \2

I-C

N

SUBSTITUTE

SHEET

WO 91/05473 PC'f/GB90/01555 2 wherein R 1 and R 7 are each independently hydrogen or C 1

-C

3 alkyl,

R

2 is hydrogen or C1-C 6 alkyl, R 3 and R 4 independently and each R 5 independently are hydrogen or C 1

-C

4 alkyl,

R

6 is a cyclohexyl group or a monocyclic or bicyclic aromatic group (for example phenyl or naphthalenyl) substituted with from 1 to 5 groups of the formula R 8 wherein R 8 is halogen, a C 1

-C

1 0 alkyl group, preferably C 3

-C

4 alkyl, more preferably t-butyl, a C 1

-C

10 alkoxy group, a trialkylsilyl group, or a phenyl, phenoxy, phenyl C1-C 2 alkylene, or phenyl alkenylene group, optionally substituted on the phenyl or phenoxy group with from 1 to 5 halogen atoms, C 1

-C

6 alkyl or C 1

-C

6 alkoxy groups, trihalomethyl groups, phenyl groups or phenoxy groups, p is 0, 1 or 2 Y is a group of the formula -(CR 9

R

9 wherein n is 27=- 3, 4.

each R 9 independently is hydrogen or C 1

-C

4 alkyl, and X~ is a suitable counter-ion. The invention also provides fungicidal compositions which contain such compounds, part 1iily1 together with an agriculturally acceptable carrier or diluent.

A number of compounds of formula I-A, I-B and I-C are novel, particularly those wherein p is 1 or 2 and n is 3 or 4. Accordingly, the invention also provides such novel compounds.

It will of course be appreciated that although the compounds of formulae I-A, I-B and I-C are illustrated as containing simple double bonds, in practice considerable delocalisation of the double bond WO 91/05473 PCT/GB90/01 555 structure will take place over the three nitrogen atoms of the compound. The compounds of the invention contain three basic nitrogen atoms, and thus can exist either in the form of the free base (formulae I-B and or a salt (formula for example a quaternary salt or an acid addition salt. The compound can thus exist in tautomeric forms, all of which are within the scope of the present invention.

R

1 and R 7 are preferably each hydrogen, methyl or ethyl more preferably hydrogen, and R 2 is preferably hydrogen or methyl, more preferably hydrogen.

Y is preferably a group of the formula

-(CR

9

R

9 3 wherein R 9 is as defined above (preferably hydrogen or methyl), more preferably a group of the formula -(CH 2 3 or -CHMeCH 2 CHMe-.

Each of groups R 4 and R5 are preferably hydrogen, group R 3 is preferably methyl, and p is preferably 1.

The group R 6 is preferably a substituted phenyl group, more preferably a 4-t- butylphenyl group or 4-trimethylsilylphenyl.

The ring containing the guanidine preferably six membe n in the definition of Y ia-e aly 3.

The terms alkyl, alkoxy, alkylene, alkenylene and the like, as used herein, are intended to include within their scope both straight and branched groups, and the terms alkenyl, alkenylene and the like are intended to include groups containing one or more than one double bonds. The term halogen and halo as used herein include chlorine, bromine, fluorine and iodine.

It will be appreciated that certain combinations of substituent groups for compounds which fall within the WO 91/05473 P~/GB90/01 555 4 definition of formula I-A, I-B and I-C given above will be impossible to prepare for steric and other chemical reasons. Such compounds are not included within the scope of the invention.

The anion X- in formula I-A may be any anion addition salt capable of forming an acid, for example chloride, bromide, acetate, stearate, benzoate or dodecylbenzenesulphonate, the chloride being preferred.

The compounds of formula I-A, I-B and I-C may be prepared by reacting a compound of the formula

R

2

II

R

6

-(CR

5

R

5 pCR 3

R

4

-NH

with a salt of the formula

R

1 N+ X~ Y

III

N

R7 wherein R 1 to R 7 Y, X and p are as defined above, and L is a suitable leaving group, for example an alkylthio group, preferably at a temperature of from to 200 0 C. The reaction may be carried out in a suitable organic solvent for example an alkanol such as n-pentanol, or in the absence of solvent.

L is preferably an alkylthio group.

The compounds of formula I-A, I-B and I-C may also be prepared by reducing a compound of formula PCr/GB90/01555 /rLC-^TI WU UYI/57.3 5

R

9 N R2

R

9

N-CR

3

R

4

(CR

5

R

5 p

R

6

N

R

9 preferably utilising hydrogen and a metallic catalyst.

The reaction may be carried out at atmospheric temperature and pressure in a polar solvent, in the presence of an acid. The compound of formula V may be prepared by reacting a compound of the formula

"R

2

II

R

6

-(CR

5

R

5 pCR3-NH with a compound of the formula

R

9 k N

R

9 L IV

R

9 wherein R 2 to R 6 and each R 9 independently, is as defined above, and L is a suitable leaving group The reaction between compound II and compound III is preferably carried out in a polar solvent at a temperature of from 50 to 200'C, in the presence of a base. Compounds of the formula II may generally be prepared by the reaction of a compound of the formula Na R 3

R

4 CNO2 with a compound of the formula: Ph 5 )p-N Ph BF4 Ph followed by reduction of the nitro group, preferably k~e 0L, WO 91/05473 6 PCT/GB90/01555 employing a metal hydride such as LiAlH 4 and when

R

2 is alkyl, alkylation with an alkylating agent, for example a haloalkane. Compound VI may be prepared according to Katrizky, de Ville and Patel Chem.

Comm. 1979, 602) from a compound of formula

R

6

-(CR

5

R

5 )p-NH 2 and 2,4,6,-triphenylpyrilium tetrafluoroborate.

Alternatively and preferably, compounds of formula I-B, wherein certain of the R 5 groups are restricted to hydrogen, may be prepared by the reaction of a compound of the formula

R

3

CH

2 NG2 with a compound of the formula

R

6

-(CR

5

R

5 p_CR 5 0 preferably in the presence of a mild base at a temperature of from 25 to 150°C, followed by reduction of the nitro group and the double bond. The reduction may be carried out, for example using a metal hydride such as LiA1H 4 at a temperature of from -80 to 100*C.

The compounds of formula I-A, I-B and I-C may be used as fungicides in particular for agricultural use, against a wide range of pathogens, for example Ascomycetes, Eumycetes and Fungi Imperfecti, in a protectant or eradicant fashion, and exhibit low phytotoxcicity to crops, in particular cereal and broadleaf crops. In particular, the compounds in accordance with the invention may be applied to the roots, seeds, or foliage of barley and other plants, for the control of various fungi, without damaging their commercial value. In particular the compounds of the present invention effectively control a variety of undesirable fungi which infest useful plant crops.

Many of the compounds are particularly effective against members of the i) Deuteromycotina such as WO 91/05473 7 PCFr/G B90/01555 Septoria nodorum (glume blotch of cereals), Pyricularia oryzae (rice-blast), Botrytis cinerea (grey mould of grapes and Fusarium Oxysporum (various wilt diseases), ii) Ascomycotina such as Pyrenophora teres (net-blotch) and Erysiphe graminis (powdery mildew), and iii) Basidiomycotina such as Puccinia recondita (leaf rust).

The compounds can be applied to the seeds, roots or foliage of cereals or other plants and will kill or control the growth of various fungi without damaging the commercial value of the said plants.

Where the acid addition salt is employed, the improved water solubility (especially of the chloride) also allows the preparation of solutions (in water or organic solvents) in which, at use rate, the addition salt is completely soluble in the spray dilution.

At least utilising the preferred embodiments of the invention a single application of the compounds can provide a residual control of powdery mildew diseases over an extended period. Also, the compounds can be effective in eliminating established barley powdery mildew infestation. Furthermore, many compounds have been found to be translocated in plants and, thus, can provide a systemic protection against powdery mildew.

The compounds of the invention may also find application as non-agricultural fu.igicides for example in medicine as antimycotics against organisms such as Candida albicans, Candida spp, Trichophyton spp, Aspergillus spp, Microsporum spp and Sporothrix spp, and also as agents against parasites such as Leishmania.

As indicated above, the invention includes within its scope fungicidal compositions- oompr ga fungicidally effective amount of a compound of formula I-A, I-B or I-C together with an inert carrier or 91/05473 PCT/GB90/01555 WO 91/05473 diluent. Such compositions may be in the form of a liquid, powder, dust or granular composition containing one or more of the active compounds in and one or more 0 inert, non-phytotoxic materials, known in the art as agricultural adjuvants and/or carriers, in solid or liquid form. Thus, for example, the active compound(s) can be admixed with one or more additives including water or other liquid carriers such as organic solvents, and petroleum distillates, surface active dispersing agents, and finely divided inert solids.

In such compositions, the active ingredients are generally present in a concentration of from 2 per cent to about 95 per cent by weight preferably from 10 per 1 cent to 95 per cent by weight and most advantageously per cent to 75 per cent by weight. The compound can be employed in the form of a solution, a diluted flowable compositions or a wettable powder composition containing 2 to 10,000 ppm of active ingredient.

2 Preferably 10 to 600 ppm are employed.

When the carrier contains a surface active agent, from about 0.1 to about 20 per cent by weight of the active ingredient is advantageously employed.

Depending upon the concentration in the composition, 2 such augmented compositions are adapted to be employed for the control of the undesirable fungi or employed as concentrates and subsequently diluted with additional inert carrier, e.g. water, to produce the ultimate treating compositions.

In general, good results can be obtained with liquid compositions containing from about 0.0001 to about 2.0 per cent by weight of the active compound in the final diluted form. With dusts, good results can usually be obtained with compositions containing from about 0.1 to about 2.j per cent or more by weight of active compound. Where e compositions are to be active compound. Where "-ie compositions are to be WO 91/05473 PCT/GB90/01555 9 applied to foliage of plants, it is preferred that the toxicant be present in an amount not to exceed about 0.8 per cent in liquid compositions and about 1.0 per cent in dusts.

In terms of hectarage application, good controls of powdery mildews can be obtained when the active ingredients are applied to growing plants at a dosage of from about 0.004 to about 4 kg/hectare. When 1 employed as fungicides for the treatment of seeds or non-living substrates, from about 0.1 to about 100 gram of active ingredient per kilogram of substrate is an effective dose.

In the preparation of dust, or wettable powder Scompositions, the toxicant products can be compounded with any of the finely divided solids, such as prophyllite, talc, chalk, gypsum, fuller's earth, bentonite, attapulgite, starch, casein, gluten, or the like. In such operations, the finely divided carrier is ground or mixed with the toxicant or wet with a solution of the toxicant in a volatile organic solvent.

Also, such compositions when employed as concentrates can be dispersed inr water, with or without the aid of dispersing agents to form spray mixtures. Dust 2 compositions are advantageously employed when treating seeds.

Granular formulations are usually prepared by impregnating a solution of the toxicant, in a volatile organic solvent onto a bed of coarsely divided attapulgite, bentonite, diatomite, or the like.

Similarly, the toxicant products can be compounded with a suitable water-immiscible inert organic liquid and a surface active dispersing agent to produce an emulsifiable concentrate which can be further diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions which may optionally contain WO91/05473 PCT/GB90/01555 10 water miscible organic co-solvents to improve the physical properties of the formulation. In such compositions, the carrier comprises an aqueous emulsion, a mixture of inert water-immiscible solvent and optional water miscible organic co-solvent, emulsifying agent, and water.

Emulsifierr which can be advantageously employed herein can be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxide or mixtures of ethylene and propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene.

Cationic emulsifiers include quaternary ammonium compounds and fatty amines. Anionic emulsifiers include the oil-soluble salts calcium) of alkylaryl sulphonic acids, oil soluble salts or sulphated polyglycol ethers and appropriate salts of phosphated polyglycol ether.

Representative organic liquids which can be employed in preparing the emulsifiable concentrates the present invention are the aromatic liquids such as xylene; propyl benzene fractions; or mixed naphthalene fractions; mineral oils substituted aromatic organic liquids such as dioctyl phthalate; kerosene; butene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, and the methyl ether of triethylene glycol. Mixtures of two or more organic WO 91/05473 PCT/GB90/01555 11 liquids are also often suitably employed in the preparation of the emulsifiable concentrate. The preferred organic liquids are xyl. and propyl benzene fractions, with xylene being most preferred.

The surface active dispersing agents are usually employed in liquid compositions and in the amount of from 0.1 to 20 per cent by weight of the combined weight of the dispersing agent and active compound. The active compositions can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.

In particular, the active compositions may contain adjuvant surfactants to enhance the deposition, wetting and penetration of the composition onto the target crop and organism. These adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will vary from 0.01 per cent to 1.0 per cent v/v based on a spray-volume of water, preferably 0.05 to 0.5 per cent. Suitable adjuvant surfactants include ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines and blends of surfactants with mineral or vegetable oils.

In such embodiments, the compounds of the present invention or compositions cc. ining the same, can be advantageously employed in combination with one or more additional pesticidal compounds. Such additional pesticidal compounds may be insecticides, nematocides, miticides, arthropodicides, or bactericides that are compatible with the compounds of the present invention in the medium selected for application and not the activity of the present compounds.

antagonistic to the activity of the present compounds.

PCT/GB90/01555 WO 91/05473 PC/GB90/01555 12 Accordingly, in such embodiments, the pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use or as an 0 additive. The compounds in combination can generally be present in a ratio of from 1:100 to 100:1.

The exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular 1 action desired, the fungal species to be controlled and the stage of growth thereof as well as the part of the plant to be contacted with the toxic active ingredient.

Thus, all of the active ingredients of the present invention and compositions containing the same may not 1 be equally effective at similar concentrations or against the same fungal species.

The compounds in accordance with the invention may be applied in the form of any of the generally used formulation types, for example as solutions, dusts, 2 wettable powders, flowable concentrates, or emulsifiable concentrates.

The invention includes within its scope a method for the control or prevention of fungal attack, which method cp. sapplying to the locus of the fungus, 2 or to a locus in which the infestation is to prevented, (for example applying to cereal grain plants), a fungicidal amount of one or more of the compounds.

A number of preferred embodii,.ants of the invention are illustrated in the following Examples.

Example 1 Preoaration of butvlphenvl)Droo-2-yl)-N'N"trimethvleneauanidinium chloride a) Preparation of 1-(4-t-butylphenyl) -2-nitroprop-1-ene 1 2 .4g of 4-t butylbenzaldehyde, 30 ml of nitroetbane and 2.9g of ammonium acetate were refluxed WO 91/05473 PCT/GB90/01555 13 together under nitrogen for 4 hours. The nitroethane was distilled off and the residue taken up in ethylacetate. This was washed twice with water, dried, filtered and the solvent evaporated off. The residue was distilled at 90'C (0.5 torr) Hg to afford a lemon yellow oil. Elemental analysis indicated the following:- C 71.3%; H 7.85%; N (calculated, C 71.2%; H 7.80%; N 1 b) Preoaration of 1-(4-t butvlohenvl)Drooan-2-amine 7 .6g of the nitroolefin prepared in above was dissolved in 150 ml dry diethylether and added dropwise to 10g of lithium aluminium hydride in 300 ml diethylether under nitrogen with stirring. On 1 completion of addition the mixture was r Ixed for 24 hours. 35 ml of triethanolamine was added over 2 hrs with cooling and then 9 ml water added dropwise. The mixture was stirred for 2 hrs and the resulting suspension of sandy consistency filtered. The solids 2 collected were washed with diethylether and the washings combined with the organic solution. This was washed, dried with MgSO4 filtered, the solvent evaporated under reduced pressure and esidue distilled at 65°C, (0.44 torr) to afford 5.4 g of an oil. NMR and IR spectra were consistent with the title compound c) Preoaration of butylphenyl) oropan-2-amino)vprimidine of l-(4-t-butylphenyl)-propan-2-amine, 2.68g of 2-chloropyrimidine and 3.05g of ethyldiisopropylamine, all in 40 ml pentanol, were refluxed under nitrogen for 24 hours. The solvent was distilled off at reduced pressure and the residue taken up in dichloromethane and washed three times with water. The organic layer was dried with MgS0 4 filtered and the solvent removed under reduced pressure. The residue was removed under reduced pressure. The residue was PCT/GB90/01555 WO 91/05473 14 chromatographed on silica gel, EtOAc/hexane to yield 3.4g of a yellowish solid. Elemental analysis indicated the following; C 75.5%; H N 14.2% (calculated, C 75.8%; H N 15.6%).

d) Ig of 2-(1-(4-t-butylphenyl)propan-2-amino) pyrimidine was dissolved in 25 cc absolute ethanol, and 150 mg of 10% palladium on charcoal and 1 ml of 2N hydrochloric acid were added. The mixture was agitated and hydrogenated at atmospheric pressure until hydrogen uptake ceased. The mixture was filtered and the solvent removed under reduced pressure to afford lg of a gum. NMR and IR spectrocopy of the product were 1 consistent with the expected structure for the title compound of Example 1.

ExamDle 2 PreDaration of N-(2-(4-t-butvlohenvl))ethvl-N',N"trimethvlene auanidinium bromide 4-t butylphenethylamine was prepared in a manner analogous to that used in steps and in Example 1, except that nitromethane was used in place of nitroethane in step 1.2g of 4-t-butylphenethylamine and 1.6g 2 S-ethyl-N,N'-trimethylenethiuronium bromide were dissolved in 9 ml ethanol and refluxed for 24 hours.

The solvent was evaporated off and the residue chromatographed on silica (CHC13/EtOH/AcOH) to afford lg of a gum. Elemental analysis indicated the 3 following C 55.2%; H 7.75%; N 11.6% (calculated, C 56.5%; H 7.70; N 12.3). NMR and IR spectra were consistent with the expected structure.

Examples 3 and 4 N-(l-(4-t-butylphenyl)prop-2-yl)-N',N"-pent-2, 4 3 diyl guanidinium acetate (Example 3) and chloride (Example 4) were prepared by methods analogous with WO 91/05473 PCT/GB90/01555 15 those used in Example 1, except that 2-chloro, 4,6 dimethyl pyrimidine was used in place of 2-chloro pyrimidine in step and in Example 5, acetic acid was used in place of hydrochloric acid. NMR and IR spectra were consistent with the expected structure.

Example Preoaration of N-(l-(4-hexvlohenvl)Droo-2-vl)-N', trimethvleneguanidinium chloride The preparation was carried out in a manner analogous to that used in Example 1, except that 4-hexylbenzaldehyde was used instead of 4-t-butyl benzaldehyde. NMR and IR spectra were consistent with the expected structure.

ExamDle 6 Preparation of N-(l-(4-(2-ohenvl)ethvl proo-2-vl)-N',N"-trimethvleneuanidinium chloride The preparation was carried out in a manner analogous to that used in Example 1, except that 4-styrylbenzaldehyde was used instead of 4-t-butylbenzaldehyde. The double bond of the styryl group was reduced in step NMR and IR spectra were consistent with the expected structure.

Example 7 PreDaration of N-(1-(4-Dhenvl)DroD-2-vl)-N', N"-trimethvlenequanidinium chloride The preparation was carried out in a manner analogous to that used in Example 1, except that 4-phenylbenzaldehyde was used instead of 4-t-butyl benzaldehyde. NMR and IR spectra were consistent with the expected structure.

Example 8 Preparation of N-(l-(3-Dhenoxv)proo-2-vl)-N', N"-trimethylenequanidinium chloride The preparation was carried out in a manner analogous to that used in Example 1, except that PCT/GB90/01555 WO 01 /lf47 yS[ 16 3-phenoxybenzaldehyde was used instead of 4-t-butyl benzaldehy.de. Elemental analysis indicated the following C 65.2%; H 6.95%; N 11.7% (calculated, C 65.9%; H 7.00%; N NMR and IR spectra were consistent with the expected structure.

Test Procedures The compounds of Examples 1 to 8 were tested in accordance with the following in vitro and in vivo test methods.

In Vitro Screen Method Test compounds are generally dissolved in acetone and made up with distilled water to give a solution with a final concentration of compound of 400 ppm and 10 per cent acetone. 2 ml aliquots of the latter solutions are pipetted into sterile petri dishes, and 18 ml of agar is then added to each dish using an automatic agar plate pourer to give a final concentration of compound of 40 ppm.

Once the aqar is set, discs of pathogens are cut from stock agar plates using a cork borer, and placed (pathogen face down) onto the test agar surface.

Pathogens used in the primary screen include:- 1. Alternaria brassicola 2. Fusarium oxysporum phaseolicola 3. Pvrenoohora teres 4. Botrvtis cinerea Pyricularia oryzae 6. Pseudocercosoorella herootrichoides.

Three pathogens are placed on each plate. Two replicates of each plate are set up and kept in an incubator at The pathogens.on plate 1 are assessed after 5 days and those on plate 2 after 8 days. The diameters of 3 the fungal colonies are measured after the incubation period and compared to the control measurements.

WO 91/05473 PCT/GB90/01555 17 Allowing for the diameter of the original disc, percentage inhibition values are then calculated.

In Vivo Screen Method Compounds are dissolved in acetone or water (as required) and made up with distilled water to give a final concentration of compound of 400 ppm (and acetone where acetone is used).

For each compound 3 replicate plants per pathogen (at the 1 leaf stage for cereals and at least the 2 leaf stage for vines) are sprayed to run off. The plants are allowed to dry at room temperature for 24 hours prior to inoculation.

Untreated control plants and plants sprayed with acetone water or water (as required) are included for each pathogen.

Method for Erysiphe graminis Hordei Barley cv. Golden Promise is used as the host plant. Seeds are sown 8 per 3" pot (plants approximately 2 weeks old). Spores are blown onto the test plants from the stock plants, which are then incubated at 20 0 C, relative humidity 70% for 7 days.

After a week symptoms are recorded. infection is scored from 3 replicate plants and expressed as a of acetone/water control plants. control is then recorded.

Method for Puccinia recondita Wheat cv. Tonic. Seeds are sown 1 cm deep in 4 rows per plastic tray 60 cm x 30 cm. Seedlings are inoculated at 1-2 leaf stage. 0.05 g of uredospores are put into 100 ml distilled water with a melting agent. This solution is sprayed onto seedlings leaving a fine coverage on the leaves. The plants are then incubated with 100% relative humidity at 15-20*C for 4 days.

infection is scored from 3 replicate plants and WO 91/05473 18 PCT/GB90/01555 expressed as a of acetone/water control plants. control is then recorded.

The results are shown in Table 1 and 2 respectively.

TABLE 1 Example Number 1 2 3 4 6 7 8 Alternaria brassicola 91 97

NT

In vitro Biological Evaluation, Per cent Efficacy of Compounds of Examples I to 8 Fusarium Pyrenophora Pseudocercosporella Botrytis oxysporum teres herpotrichoides cinerea 64 86 82 100 40 80 NT 78 70 79 64 NT 72 77 45 NT 78 78 67 NT 88 83 67 NT 67 14 50 NT 75 38 100 NT Pyricullaria oryzae.

33

NT

63 59 58 74 NT Not Tested 37, 105/37,119 WO 91/05473 PTG9/15 PCT/GB90/01555 TABLE 2 In vitro Biological Evaluation Per cent Efficacy Of Comoounds of Examoles 1 to Example Number Erys iphe gram in is 100 Puccini a recondita

NT

0 82 Phytotoxicity M% 100 100 100 100 NT Not Tested 37,105

Claims

1. An agricultural fungicidal compositionfij\&r~lia a compound of the formula: CR 5 R 5 P-R 6 R/ Y N N CR 3 R 4 (CR 5 R 5 P-R 6 I-B ,cR3R4CR5R5)P-R I-c wherein RI and R7are each independantly hydrogen or iC alkyl, R 2 is hydrogen or C 1 -C 6 alkyl, Rand R 4 independently, and each R 5 independently are hydrogen or C 1 -C 4 alkyl, R 6 is a cyclohexyl group or a monocyclic or bicyclic aromatic group, substituted with from 1 to 5 groups of the f ormulaR wherein R 8 is halogen, a C 1 -C 10 alkyl group, a C-I alkoxy group, a tri-C 1 -C 4 -alkylsilyl group, or a phenoxy, WO 91/05473 PCT/GB90/01555 -22- phenyl, phenyl-C 1 -C 2 -alkylene, or phenyl-C 2 -alkenylene group, each optionally substituted on the phenyl or phenoxy group with one or more of halogen atoms, C 1 -Cg alkyl or C 1 -C 6 alkyl or CI-C 6 alkoxy groups, trihalomethyl groups, phenyl groups or phenoxy groups. p is 0, 1 or 2, Y is a group of the formula -(CR 9 R 9 wherein n is r- 3, ov F each R 9 independently is hydrogen or C 1 -C 4 alkyl and X is a suitable counter-ion, together with an agriculturally acceptable carrier or diluent.

2. A composition as claimed in Claim 1, wherein R 1 and R 7 are each independently hydrogen, methyl or ethyl.

3. A composition as claimed in Claim 2, wherein R 1 and R 7 are each hydrogen.

4. A composition as claimed in any one of the preceding Claims, wherein Y is a group of the formula -(CR9Rg)3-, wherein R 9 is as defined in Claim 1. A composition as claimed in Claim 2, wherein Y is a group of the formula or -CHMeCH 2 CHMe-.

6. A composition as claimed in any one of the preceding Claims, wherein R 2 is hydrogen.

7. A composition as claimed in any one of the preceding Claims, wherein R 3 is methyl.

8. A composition as claimed in any one of the preceding Claims, wherein R 4 and R5 are each hydrogen. WO 91/05473 PC/G B90/01555 -23-

9. A composition as claimed in any one of the preceding Claims, wherein p is 1. A composition as claimed in any one of the preceding Claims, wherein R 6 is substituted phenyl.

11. A composition as claimed in Claim 10, wherein R 6 is 4-t-butylphenyl or 4-trimethylsilylphenyl.

12. A method of preparing a composition as claimed in any one of the preceding Claims, which method dss- combining the said compound of formula I-A, I-B, I-C with an agriculturally acceptable currier or diluent.

13. A compound of the formula I-A, I-B or I-C as defined in Claim 1, wherein p is 1 or 2.-rd n is 4

14. A method of preparing a compound of formula I-A, I-B, or I-C as defined in Claim 1, which method) MiMpi- reacting a compound of the formula R 2 R 6 (CR 5 R 5 pCR 3 R 4 NH I I With a salt of the formula N Y\ III N wherein R 1 to R 7 Y, and p and X are as defined in Claim.'i, 6 5 5 3 4 R 6 (CR R )p CR R NH With a salt of the formula 01 wherein R to RY, and p and X are as defined in claim 1, -23 a- WO 91/05473 PPe/GB90/01 555 -24- and L is a suitable leaving group. A method as claimed in Claim 14, wherein L is an alkylthio group.

16. A method of preparing a compound of formula A, I-B, or I-C as defined in Claim 1, which method emnpricSz reducing a compound of the formula. R 9 N R 2 R9- NR-CR3R(CR5R5) pR 6 U R

17. A method as claimed in l1aimLIs, wherein the reduction is carried out using hyd-ogen and a metallic catalyst in the presence of an acid.

18. A method as claimed in Claim 16 or Claim 17 for the preparation of a compound of the formula I-A I-B or I-C as defined in Claim 1, wherein the said compound of formula V is prepared by reacting a compound of the formula R 2 R 6 (CR 5 R 5 CR 3 R 4 -NH II R 6 (CF~R) CR R -NH -24 a- WO 91/0547.3 PCT/GB90/01555 with a compound of the formula wherein R 2 to R 6 and each R 9 independently, is as defined in Claim 1, and L is a leaving group.

19. A method as claimed in Claim 18, wherein the leaving group is a halogen, and the reaction is carried out in the presence of a base. A method for the control or prevention of fungal infestation, which method mprs~tapplying to the locus of the fungus, or in which the infestation is to be prevented, a composition as claimed in any one of Claims 1 to 11, or a compound as claimed in Claim 13.

21. A composition according to claim 1 substantially as hereinbefore described with reference to the examples.

22. A method according to claim 14 substantially as hereinbefore described with reference to the examples. DATED 17 JANUARY 1994 PHILLIPS ORMONDE FITZPATRICK Attorneys For: DOW CHEMICAL COMPANY LIMITED -26- INTERNATIONAL SEARCH REPORT International Application No PCT/GB 90/01555 I. CLASSIFICATION OF SUBJECT MATTER (if several classification symbols apply, indicate all)o According to International Patent Classification (IPC) or to both National Classification and IPC A 01 N 43/48, C 07 D 239/14, 243/04//(A 01 N 43/48, 43:62, 43:54. 43:50) II. FIELDS SEARCHED Minimum Documentation Searched 7 Classification System Classification Symbols A 01 N; C 07 D Documentation Searched other than Minimum Documentation to the Extent that such Documents are Included in Fields Searched 8 III. DOCUMENTS CONSIDERED TO BE RELEVANT 9 Category Citation of Document," with indication, where appropriate, of the relevant passagesl 2 Relevant to Claim No. 13 Y Chemical Abstracts, volume 110, no. 23, 5 June 1-20 1989, (Columbus, Ohio, US), Glushkov, R.G. et al.: "Synthesis and pharmacologic study of novel substituted guanidines and 2-amino-2-imidazolines see page 740, abstract 212684r, Khim.-Farm. Zh. 1988, 22(

951- 955 Y US, A, 2988478 GORDON) 13 June 1961, 1-20 see the claims Y EP, Al, 0001663 PHILIPS' 1-20 GLOEILAMPENFABRIEKEN) 2 May 1979, see the claims Special categories of cited documents:10 later document published after the international filing date docu>ent defining the 1 r ich is not or priority date and not in conflict w th the application but "A dc n d d efinin th eneral state of the art which is not cited to understand the prncple or theory underlying the considered to be of pa ricular relevance invention E" earlier document but published on or after the international X' document of particular relevance the claimed invention Sd cannot be considered novel or cannot be considered to document which may throw doubts on priority claim(s) or involve an inventive step which s cited to establish the pubication date of anotherimed I citation or other special reason (as specified) document of particular relevance, the claimed invention cannot be considered to involve an inventive step when the d me ferring to an oral disclosure, use, exhibition or document is combined with one or more other such docu- oth dO-ment referring to a oral discsosre, use exhibition or ments, such combination being obvious to a person skilled othr means in the art. docuhnent published prior to the international filing date but document member of ihe same patent family later han the priority date claimed patent family IV, CERTIFICATION Dal:e of the Actual Completion of the International Search Date of Mailing of this International Search Report 19th Deceiber 1990 4. 01. 91 International Searching Authority Signature of Authorized Officer EUROPEAN PATENT OFFICE i. P L 7 Form PCTIISA/210 (s cond sheet) (January 1985) International Application No. PCT/GB 90/01555 111. DOCUMENTS CONSIDERED TO BE RELEVANT (CONTINUED PROM THE SEC~ND SHEETI Categoryj Citation of Document, with indication, where appropriate, of the relevant passages JRelevant to Claim No DE, Al, 2941658 (IJUPHAR INTERNATIONAL RESEARCH 24 April 1980, see the claims CH, A5, 630507 (CIBA-GEIGY AG) 30 June 1982, see the claims EP, A2, 0323757 (UBE INDUSTRIES LTD.) 12 July 1989, see the claims; page 24, compound 106 1-20 1-20 1-20 Form PCT/ISA/210 (extra sheot) (January 1985) ANNEX TO THE INTERNATIONAL SEARCH REPORT ON INTERNATIONAL PATENT APPLICATION NO.PCT/GB 90/01555 SA 40771 This annex lists the patent family members relating to the patent documents cited in the above-mentioned international search report. The members are as contained in the European Patent Office EDP file on 28/11/90 The European Patent office is in no way liable for theseparticulars which are merely given for the purpose of information. Patent document Publication Patent family Publication cited in search report date member(s) date US-A- 2988478 13/06/61 NONE EP-Al- 0001663 02/05/79 AU-B- 521181 18/03/82 AU-D- 4075478 24/04/80 CA-A- 1105845 11/08/81 JP-C- 1375925 22/04/87 JP-A- 54063080 21/05/79 JP-B- 61041353 13/09/86 NL-A- 7711390 20/04/79 US-A- 4374143 15/02/83 US-A- 4396617 02/08/83 DE-A1- 2941658 24/04/80 AU-D- 5175279 24/04/80 BE-A- 879425 15/04/80 FR-A- 2438424 09/05/80 GB-A- 2038305 23/07/80 JP-A- 55113705 02/09/80 NL-A- 7810350 18/04/80 630507 30/06/82 AU-D- 3065477 24/05/79 CA-A- 1104143 30/06/81 CA-A- 1109787 29/09/81 DE-A- 2750902 24/05/78 FR-A-B- 2380733 15/09/78 FR-A-B- 2381030 15/09/78 GB-A- 1592699 08/07/81 JP-A- 53063378 06/06/78 NL-A- 7712401 18/05/78 OA-A- 5802 31/05/81 US-A- 4254133 03/03/81 EP-A2- 0323757 12/07/89 JP-A- 2085263 26/03/90 US-A- 4931455 05/06/90 For more details about this annex: see Official Journal of the European patent Office, No. 12/82 EPO FORM P0479