GB2187733A - Imidazole compounds useful as fungicides - Google Patents

Abstract

1. Fungicidally active imidazole compounds of general formula I:- <IMAGE> wherein X is O or S; R1 is alkenyl; R2 is alkyl, cycloalkyl, alkenyl or alkynyl; R3 is optionally substituted phenyl and A is alkylene; together with the preparation of such compounds, fungicidal compositions containing them and their use as fungicides.

Description

SPECIFICATION Fungicides This invention relates two certain imidazolyl compounds, the preparation of such compounds,fungicidal com- positions containing them, and to their use as afungicide.

UK Patent Application. No. 2129798 discloses fungicidal activity in compounds of the general formula:

wherein, inter alia, R is halophenyl; R1 is alkyl; R2 is a 5-membered heterocyclic ring containing 1 or 2 nitrogen atoms and optionally ring substituted by 1 or 2 alkyl groups; Zis oxygen, X is oxygen; and alkisan alkylene group.

It has now been formed that useful fungicidal activity is present in imidazolyl compounds bearing an N-alkenyl ring substituent. Accordingly, the present invention provides imidazole compounds of the general formula l:-

wherein X represents an oxygen orsulphur atom; R1 represents an alkenyl, preferably propenyl, group; R2 represents an optionally substituted alkyl, cycloalkyl, alkenyl, or alkynyl group; P3 represents an optionally substituted phenyl group; and A represents an alkylene group.

When any of the foregoing substituents represents or contains an alkyl, alkenyl, or alkynyl substituent group, this may be linear or branched and may contain upto 12, preferably upto 6, and especially from 1 to4, carbon atoms, suitable examples being methyl, ethyl, propyl, butyl, propenyl and propynyl. When they represent a cycloalkyl group this may contain from 3 to 10, preferably 3 to 8, carbon atoms, and is suitably cyclohexyl.When they represent an alkylene group,this may be linear or branched and may contain up to 10, preferably up to 6, carbon atoms and preferably should have a chain length of at most 5 carbon atoms.When any of the foregoing substituents are designated as being optionally substituted, the substituted groups which are optionally present may be any of those customarily employed in the development of pesticidal compounds, and/orthe modification of such compounds to influencetheirstructure/activity, persistence, penetration or other property. Specific examples of such substituents include halogen, especiallyfluorine, chlorine or bromine, atoms, and nitro, cyano, hydroxyl, alkyl, haloalkyl, and alkoxy groups; in the case of halogen substituted alkyl groups, a particular preferred example istrifluoromethyl.

Preferably X represents an oxygen atom; R1 represents an alkenyl group of up to 6 carbon atoms, especially allyl; R2 represents an alkyl group of 1 to 6 carbon atoms, especially methyl, ethyl, propyl, or butyl, an alkenyl or alkynyl group of up to 6 carbon atoms, especially propenyl or propynyl, or a cycloalkyl group of 3to 8 carbon atoms, especially cyclohexyl; R3 represents a halophenyl group, especially di- ortri-chlorophenyl, oralkylphenyl, especially mesityl; and A represents an alkylene group of unto 10, especially upto 6, carbon atoms in which the chain length is at most 5 carbon atoms, especially ethylene.

The invention also provides a process for the preparation of imidazole compounds of formula I defined abovewhich comprises reacting an amine offormula II:

with an imidazolyl acid oracyl halide oftheformula Ill:

wherein Xis a hydroxyl group or halogen, preferably chlorine, atom. The reaction is conveniently carried out in an inert organic solvent, such as pyridine, and proceeds smoothly at room temperature. When the acyl halide of the imidazolyl acid is the chosen reactant, it may conveniently be prepared from the free acid by reaction with thionyl chloride.

In another aspect, the invention provides a fungicidal composition which comprises a carrier and, as active ingredient, a imidazole compound offormula las defined above; and also a method of making such a composition which comprises bringing a compound offormula I into association with at least one carrier.

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 mayfor example be a plant, seed or soil, orto 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. Preferably compositions according to the invention contain 0.5 to 95% by weight of active ingredient.

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; caicium 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; 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 ketoneand cyclohexanone; ethers; aromaticoraraliphatic 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.

Agricultural compositions are often formulated and transported in a concentrated form which issubsequ ently diluted bythe user before application. The presence of small amounts of a carrier which is a surfaceactive 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.

Asurface-active agent may be an emulsifying agent, a dispersing agentor a wetting agent; it may be nonionic or ionic. Examples of suitable surface-active agents include the sodium our calcium salts of polyacrylic acids and lignin sulphonic acids; the condensation 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 examplep-octylphenol orp-octylcresol, with ethylene oxide and/or propylene oxide; sulphates or sulphonates of these condensation products; alkali oralkaline earth metal salts, preferably sodium salts, of sulphuric orsulphonic acid esters containing at least 10 carbon atoms in the molecule,forexample sodium lauryl sulphate, sodium secondary alkyl sulphates, sodium salts of sulphonated castor oil, and sodium alkylaryl sulphonates such as dodecylbenzene sulpho- nate; 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 or75% w of active ingredient and usually contain in addition to solid inert carrier, 3-10% w of a dispersing agent and, where necessary, 0-1 O% 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 are diluted in the field with further solid carrierto give a composition usually containing 1/2-10% 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 orimpregnation techniques. Generally, granules will contain 1/2-75% w active ingredient and 0-1 0%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 0-50%w/v active ingredient, 2-20% w/v emulsifiers and 0-20% w/v of other activeadditives such as stabilisers, penetrants and corrosion inhibitors. Suspension concentrates are usually compounded so asto obtain a stable, non sedimenting flowable product and usually contain 1 0-75%wactive ingredient, 0.5-1 w of dispersing agents, 0.1-10% w of suspending agents such as protectivecolloids and thixotropic agents, 0-1 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.

Aqueous dispersions and emulsions, for example compositions obtained by diluting a wettable powder our 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 orthe oil-in-watertype, and may have a thick 'mayonnaise'-like consist- ency.

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

Of particular interest in enhancing the duration of the protectant activity of the compounds ofthis invention is the use of a carrier which will provide a slow release ofthefungicidal 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 fungicide of an imidazole compound ofthe general formula I as defined above, and a method for combating fungus at a locus, which comprises treating the locus, which mayforexample be plants subjectto orsubjected to fungal attack, seeds of such plants orthe medium in which such plants are growing or are to be grown, with such a compound.

The present invention is of wide applicability in the protection of crop plants againstfungal attack. Typical crops which may be protected includes vines, grain crops such as wheat and barley, rice, 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 will be further understood from the following Examples.

Example I Preparation or of N-ln-prop yll, N-( 1-ally'-54mic'azolylcarhon yl)-ethanolamine, 2,4,6-trichlorophenylether 1 -Allyl-5-imidazoie carboxylic acid (19) ways refluxed in thionyl chloride (30mi) for 2 hours and the excess reagent was evaporated off under reduced pressure. The residue was dissolved in pyridine, cooled in an ice bath to which N-(n-propyl)ethanolamine, 2,4,6-trichlorophenylether (1.86g) in pyridine (1 5ml ) was added dropwise and the reaction stirred at room temperature overnight. The solvent was evaporated off and the residue diluted with water and extracted with methylene chloride.The combined organic extracts were washed with water, dried (MgSO4) and the solvent evaporated off to leave an oil. Flash chromatography on silica using 5% methanol/ether as eluantyielded the desired product as an oil.

Analysis Calc. C 51.8; H 4.8; N 10.08 Found C48.4; H4.5; N9.2 Examples 2-4 Following a proceduresimilartothatdescribed in Example 1,furtherN-allyl imidazoleethanolaminederi vatives were prepared, whose analyses are given in Table I below; all of the compounds were isolated as oils.

In this Table,the compounds are identified by referenceto the substituents in thefollowing formula:-

Table I Ex. R2 Z. Analysis No. C H N 2 CsH7(n) H Found 55.6 4.9 10.8 Cain. 56.5 5.5 11.0 3 C2H5 CI Found 48.3 4.4 10.1 Calc. 50.7 4.5 10.4 4 C4H9(iso) Cl Found 51.9 5.3 8.3 Calc. 53.0 5.1 9.2 Example 5 Fungicidal activity The fungicidal activity of compounds of the invention was investigated by means of the following tests.

(a) Activity against wheat leafspot (Leptosphaeria nodorum; Ln.) The test is a direct antisporulant one, using a foliar spray. Leaves of wheat plants (cv Mardler), at the single leaf stage, are inoculated by spraying with an aqueous suspension containing 8x 1 spores/ml. The inocula- ted plants are kept for 24 hours in a high humidity compartment prior to treatment.The plants aresprayed with a solution ofthe test compound in a mixture of acetone and water (50:50v/v) containing asurfactant ("TWEEN 20" (trademark) a polyoxyethylene sorbitan estersurfactant) at 0.04%w/v, using a moving track sprayer which delivers 620 1/ha, and the concentration of active material is calculated to give an application rate of 1 kg/ha. After drying, the plants are kept for 5 days under normal glasshouse conditions, followed by assessment. Assessment is based on the percentage of leaf area covered by sporulation compared with that on leaves of control plants.

(b) Activityagainstbarleypowderymlldew (Erysiphe graminis f.sp. hordei; Eg) The test is a direct antisporulant one, using a foliar spray. Leaves of barley seedlings, (cv. Golden Promise) are inoculated by dusting with mildewconidia one day priorto treatment with the test compound. The inoculated plants are kept overnight at glasshouse ambient temperature and humidity prior to treatment. The plants are sprayed with the test compound at a dosage of 1 kilogram of active material per hectare using a tracksprayeras described under (a). After drying, plans are returned to a compartment at ambienttemperature and humidity for up to 7 days, followed by assessment. Assessment is based on the percentage of leaf area covered by sporulation compared with that on leaves of control plants.

(c) Activityagainst tomato early blight (Alternaria solani;As) This test measures the contact prophylactic activity of test compounds applied as a foliarspray.

Tomato seedlings (cv Outdoor Girl) are grown to the stage at which the second true leaf is expanded. The plants aretreated using a tracksprayeras described under (a). Test compounds are applied as solutions or suspensions in a mixture of acetone and water (50:50v/v) containing 0.04% surfactant ("TWEEN 20" -Trademark).

One day aftertreatmentthe seedlings are inoculated by spraying the adaxial leaf surfaces with a suspension ofA. solaniconidia containing 10,000 spores/ml. For3 days after inoculation plants are kept moist in a glasshouse compartment at or near 100% RH and 21"C. Thereafter plants are kept under humid, but not saturated, conditions.

Disease is assessed 7 days after inoculation, based on the density and spread of lesions.

(d) Activity against wheat eyespot hPseudocercosporella herpotrichoides; Ph) This test measures the in vitro activity of compounds against the fungus causing wheateyespot The Test Compound is dissolved or suspended in acetone and is added to molten half strength Potato Dextrose Agarto give a final concentration of 100ppm compound and 3.5% acetone. After agar has set, plates are inoculated with 6mm diameter plugs of agar/mycelium taken from a 14 day old culture of P. herpotrichoides.

Plates are incubated at 20"C fo r 12 days and radial growth from the inoculation plug is measured. Growth is compared with that on an acetone control and the activity is converted to the 0-2 scale.

The extentof disease control in all the above tests is expressed as a rating compared with a diluentsprayed-control according to the criteria: 0 = less than 50% disease control 1 = about 50-80% disease control 2 = greaterthan 80% disease control The results of these tests are set out in Table 1 below.

Table 1 Jest Compound FungicidalRating of Ex. No. Eg Ln Ph As 1 2 2 2 2

Claims (17)

1. Imidazole compounds ofthegeneral formula I:

wherein X represents an oxygen or sulphur atom; R1 represents an alkenyl group; R2 represents an option- ally substituted alkyl, cycloalkyl, alkenyl or alkynyl group; R3 represents an optionally substituted phenyl group; and A represents an alkylene group.

2. Compounds as claimed in claim 1 wherein X represents an oxygen atom; R1 represents an alkenyl group of 2to 6carbon atoms; R2 represents an alkyl, alkenyl oralkynyl group of unto 6 carbon atoms, ora cycloalkyl group of to 8 carbon atoms; R3 represents a halophenyl or alkylphenyl group; and A represents a straight or branched chain alkylene group of 1 to 10 carbon atoms wherein the chain length is at most 5 carbon atoms.

3. Compounds as claimed in claim 2wherein R3 represents a di-ortri- halophenyl or mesityl group, andA represents an ethylene group.

4. Compounds as claimed in claim 3 wherein R1 represents an allyl group; R2 represents an ethyl, propyl or butyl group; and B3 represents a di- ortrichlorophenyl group.

5. Compounds as claimed in claim 1 and specifically named in anyone of Examples 1-4 herein.

6. Frocessforthe preparation of an imidazole ofthegeneral formula las defined in Claim 1,whichcomprises reacting an amine offormula Il

with an imidazolyl acid or acyl halide of the general formula Ill:-

wherein Xis a hydroxyl group or a halogen atom.

7. Process as claimed in claim 6 wherein Xis a chlorine atom and the reaction is carried out in an inert organic solvent.

8. Process as claimed in claim 6 carried outsu bstantially as hereinbefore described with particular referenceto Example 1.

9. An imidazole compound as claimed in claim 1, whenever prepared by a process as claimed in any one of claims 6-8.

10. Fungicidal composition which comprises a carriertogetherwith, as active ingredient, an imidazole compound as claimed in anyoneofclaims 1-5or9.

11. Compositions as claimed in claim 10 which comprise at leasttwo carriers, at ieast one of which is a surface-active agent.

12. A composition as defined in claim 10 substantially as hereinbefore defined.

13. Method for making fungicidal composition as defined in claim 10 which comprises bringing an im- idazole compound as claimed in claim 1 into association with at least one carrier.

14. Method of combating fungus at a locus, characterized by treating the locus with a fungicidally effective amount of a compound as claimed in any one of claims 1-5 or9 ora composition as claimed in any one of claims 10-12.

15. Method as claimed in claim 14, wherein the locus comprises plants subject to or subjected to fungal attack, seeds of such plants, orthe medium in which the plants are growing or are to begrown.

16. A method as claimed in claim 15, substantially as hereinbefore defined.

17. The use of a fungicide of a compound offormula las defined in any one of claims 1-5or9.