WO1995011899A1 - Pyrimidine derivatives - Google Patents

Abstract

The invention relates to certain pyrimidine derivatives of general formula (I), in which R?1, R2 and R3¿ independently represent a hydrogen or halogen atom, nitro, cyano, hydroxyl, carboxyl or optionally substituted alkyl, alkenyl, alkynyl, alkoxy, amino, alkoxycarbonyl, alkanoyl, cycloalkyl, alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, alkylamido or phenyl group; n represents an integer from 1 to 3; R?4, R5, R6, R7, R8 and R9¿ independently represent a hydrogen atom or an optionally substituted alkyl group; and R?10 and R11¿ independently represent a hydrogen atom or an optionally substituted alkyl or aryl group; or R?10 and R11¿ together represent an optionally substituted alkylene or alkenylene chain; with the proviso that R?7, R8, R9, R10 and R11¿ do not simultaneously represent a hydrogen atom; processes for their preparation, compositions containing such compounds and their use as biocides.

Description

PYRIMIDINE DERIVATIVES

This invention relates to certain pyrimidine derivatives, processes for their preparation, compositions containing such compounds and their use as biocides.

EP-A-O 519 211 generically discloses 4-aminopyrimidine derivatives of the general formula

in which R¹ represents hydrogen, halogen, C_1-4 alkyl or C_3-6 cycloalkyl; R² represents hydrogen, C_1-4 alkyl, halogen, trifluoromethyl, C_1-4 alkoxy, C_1-4 haloalkoxy, C_1-4 alkoxy-C_1-4 alkyl, C_1-4 alkylthio, C_1-4 alkylthio-C_1-4 alkyl, C_1-4 alkylamino, C_1-4 dialkylamino or C_3-6 cycloalkylamino; R³ represents, inter alia, hydrogen, C_1-4 alkyl, C_1-4 alkoxy, C_1-4 haloalkoxy, C_1-4 alkylthio, halogen, nitro or C_1-4 dialkylamino;

R⁴ represents hydrogen or optionally substituted carbamoyl; R⁵ represents hydrogen, C_1-8 alkyl or C_3-6 cycloalkyl; and Q represents, inter alia, an unsubstituted dioxolanyl group.

These compounds are said to be useful as pesticides, especially as insecticides, acaricides, nematocides and fungicides.

However, no specific examples are given in which Q represents a dioxolanyl group, or even a remotely similar group, despite the disclosure of more than 200 specific examples.

It has now been discovered that certain pyrimidine derivatives which are substituted by a substituted

dioxolanylalkylamino group possess biocidal activity. In particular, these pyrimidine derivatives exhibit good activity against certain phytopathogenic fungi, especially those causing diseases in cereal crops such as Erysiphe graminis, as well as insecticidal, acaricidal and nematocidal activity.

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

in which

R ¹, R² and R³ independently represent a hydrogen or halogen atom, nitro, cyano, hydroxyl, carboxyl or optionally substituted alkyl, alkenyl, alkynyl, alkoxy, amino, alkoxycarbonyl,

alkanoyl, cycloalkyl, alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, alkylamido or phenyl group;

n represents an integer from 1 to 3;

R⁴, R⁵, R⁶, R⁷, R⁸ and R⁹ independently represent a hydrogen atom or an optionally substituted alkyl group; and

R¹⁰ and R¹¹ independently represent a hydrogen atom or an optionally substituted alkyl or aryl group; or

R¹⁰ and R¹¹ together represent an optionally substituted alkylene or alkenylene chain;

with the proviso that R⁷, R⁸, R⁹, R¹⁰ and R¹¹ do not

simultaneously represent a hydrogen atom.

When the compounds of this invention contain an alkyl, alkenyl or alkynyl group, this may be linear or branched and may contain up to 12, preferably up to 6 and especially up to 4, carbon atoms. An alkylene or alkenylene chain may contain 4 to 8, preferably 5 to 7, carbon atoms. A cycloalkyl group may contain from 3 to 8, preferably 3 to 6, carbon atoms. An aryl group may be any aromatic hydrocarbon group, especially a phenyl or naphthyl group. When any of the foregoing substituents 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, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl,

alkoxycarbonyl, carboxyl, alkanoyl, cycloalkyl, alkylcycloalkyl, cycloalkylalkyl, alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, alkylamido and phenyl groups. Additionally, when R¹⁰ and R¹¹ together represent an alkylene or alkenylene chain, this may be optionally substituted by a further alkylene, alkenylene or alkadienylene chain preferably containing from 3 to 5 carbon atoms. 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. When any of the foregoing substituents represents or contains a cycloalkyl substituent group, this may contain from 3 to 8, preferably 3 to 6, carbon atoms. Typically, 0-3 substituents may be present, most commonly 0 or 1.

Preferably, R¹, R² and R³ independently represent a hydrogen or halogen atom or an amino, C_1-6alkyl, C_2-6alkenyl or C_1-6alkoxy group, each group being optionally substituted by one or more substituents selected from halogen atoms, nitro, cyano, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, C_1-6haloalkoxy, C_1-6alkylamino, di-C_1-6 alkylamino, C_1-6alkoxycarbonyl, carboxyl, C_1-6alkanoyl, C_1-6cycloalkyl and phenyl groups. More preferably, R¹, R² and R³ independently represent a hydrogen or halogen atom or an amino, C_1-4alkyl, C_2-4alkenyl or C_1-4alkoxy group, each group being optionally substituted by one or more substituents selected from halogen atoms, nitro, cyano, C_1-6 alkyl and phenyl groups. Preferably, R⁴ represents a hydrogen atom or a C_1-6alkyl group optionally substituted by one or more halogen atoms.

More preferably, R⁴ represents a hydrogen atom or a C_1-4alkyl (especially methyl) group optionally substituted (but preferably unsubstituted) by one or more halogen atoms.

It is also preferred that each R⁵ and R⁶ independently represents a hydrogen atom or a C_1-6alkyl group optionally substituted by one or more halogen atoms.

More preferably, each R⁵ and R⁶ independently represents a hydrogen atom or a C_1-6 alkyl (especially methyl) group.

Preferably, n is 1 or 2.

It is further preferred that R⁷, R⁸ and R⁹ independently represent a hydrogen atom or a C_1-6 alkyl group optionally substituted by one or more halogen atoms.

More preferably, R⁷, R⁸ and R⁹ independently represent a hydrogen atom or a C_1-4 alkyl (especially methyl) group

optionally substituted (but preferably unsubstituted) by one or more halogen atoms.

Preferably, R¹⁰ and R¹¹ independently represent a hydrogen atom or a C_1-8alkyl or phenyl group or R¹⁰ and R¹¹ together represent a C_4-8alkylene chain; each group or chain being optionally substituted by one or more substituents selected from halogen atoms, nitro, cyano, hydroxyl, C_1-6 alkyl, C_1-6

haloalkyl, C_1-6alkoxy, C_1-6haloalkoxy, amino, C_1-6alkylamino, di-C_1-6alkylamino, C_1-6 alkoxycarbonyl, carboxyl, C_1-6

alkanoyl, C_3-8 cycloalkyl, C_1-6alkyl-substituted C_3-8

cycloalkyl, C_3-8cycloalkyl-C_1-6alkyl and phenyl groups, or, in the case where R¹⁰ and R¹¹ together represent a C_4-8alkylene chain, optionally substituted by a C_3-5alkylene chain.

More preferably, R¹⁰ and R¹⁰ independently represent a hydrogen atom or a C_1-6 alkyl or phenyl group, each group being optionally substituted by one or more substituents selected from halogen atoms, nitro, cyano, hydroxyl, C_1-4alkyl, C_1-4haloalkyl, C_1-4alkoxy, C_1-4haloalkoxy, amino and C_1-4alkyl- substituted C_3-6 cycloalkyl groups; or R¹⁰ and R¹¹ together represent a C_5-7 alkylene chain optionally substituted by one or more substituents selected from C_1-6alkyl, C_1-6haloalkyl, C_1-6alkoxy, C_1-6haloalkoxy, C_3-6 cycloalkyl, C_3-6cycloalkyl-C_1-4 alkyl and phenyl groups or optionally substituted by a C_1-6 alkylene chain.

A particularly preferred sub-group of compounds of formula I is that in which R¹ represents a hydrogen atom or a methyl, propyl or styryl group; R² represents a chlorine atom or a methyl, ethyl, methoxy, ethoxy, propoxy, butoxy, methylamino, dimethylamino, phenylamino or methyl-hexylamino group; R³ represents a hydrogen or chlorine atom or a methyl group; R⁴,

R⁵, R⁷, R⁸ and R⁹ independently represent a hydrogen atom or a methyl group; n is 1 or 2; R⁶ represents a hydrogen atom; R¹⁰ and R¹¹ independently represent a hydrogen atom or a methyl, ethyl, propyl, butyl, pentyl, trimethylcyclohexylethyl, phenyl, butylphenyl, benzyl or phenethyl group; or R¹⁰ and R¹¹ together represent a pentamethylene, propylpentamethylene, butylpentamethylene, pentylpentamethylene, cyclohexylpropylpentamethylene, phenylpentamethylene, tetramethylene-pentamethylene or

heptamethylene chain.

It should also be appreciated that compounds of formula I have chiral centres and are therefore capable of existing as different isomers, that is, enantiomers and diastereomers. 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 which comprises reacting a compound of the general formula

in which n, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸ and R⁹ are as defined above, with a compound of the general formula <

in which R¹⁰ and R¹¹ are as defined above, in the presence of an acid.

The acid may be any substance which provides an acidic medium for the reaction. However, the acid is preferably an inorganic or organic acid. Suitable inorganic acids include mineral acids such as hydrochloric and sulphuric acids.

Suitable organic acids include ethanoic acid and sulphonic acids, especially para-toluene- sulphonic acid.

Suitably, the reaction takes place in the presence of an organic solvent, such as trichloromethane, benzene or toluene.

The reaction is preferably carried out at a temperature in the range from ambient temperature (about 15°C) to the reflux temperature of the reaction mixture, the preferred temperature being reflux temperature.

Compounds of formula II, which also form part of the invention, may be prepared by reacting a compound of the general formula

in which n, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸ and R⁹ are as defined above, with an oxidising agent. Suitable oxidising agents include potassium permanganate or, especially, osmium tetroxide, especially a catalytic amount thereof together with a

regeneration reagent, such as N-methylmorpholine-N-oxide. The reaction is suitably carried out in a polar solvent, for instance, an alcohol such as tert-butanol, or acetone in the presence of water. Preferably, the reaction is carried out at a temperature in the range from 30°C to 70°C, the preferred reaction temperature being in the range from 40°C to 60°C.

Compounds of formula IV may be prepared by reacting a compound of the general formula

m which R¹, R² and R³ are as defined above and Hal represents a chlorine or bromine atom with a compound of the general formula

in which n, R⁴, R⁵, R⁶, R⁷, R⁸ and R⁹ are as defined above.

Preferably, the reaction is carried out at the reflux

temperature of the reaction mixture in the presence of a base, for instance, an amine such as triethylamine, and a solvent, for instance an alcohol such as ethanol. In some cases, an excess of the compound of formula VI may serve as solvent and base. Compounds of formula V may be prepared by reacting a compound of the general formula

in which R¹, R² and R³ are as defined above, with a halogenating agent, such as phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride and phosphorus tribromide. Preferably, the reaction is carried out at the reflux temperature of the reaction mixture.

Compounds of formulae III, VI and VII are known compounds or can be prepared by processes analogous to known processes.

Compounds of general formula I exhibit biocidal, that is, fungicidal and/or pesticidal, particularly insecticidal, acaricidal and/or nematocidal, activity. Accordingly, the invention further provides a biocidal 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.

Biocidal 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 ½-10% 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 ½-75% 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 0-20% 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, 0.5-15% 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 biocidal 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 biocide 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 and/or pests at a locus, which comprises treating the locus, which may be for example plants subject to or subjected to fungal attack or attack by pests, 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 vines, 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 8-(1,1-dimethylpropyl)-2-[(2,6-dimethylpyrimidin-4-ylamino)methyl]-1,4-dioxaspiro [4.5] decane

(n=1; R¹=R²=CH₃; R³=R⁴=R⁵=R⁶=R⁷=R⁸=R⁹=H; R¹⁰/ R¹¹=3-C(CH_H)₂CH₂CH₃ pentamethylene)

(i) Preparation of 4-chloro-2,6-dimethylpyrimidine

A mixture of 2,6-dimethyl-4-hydroxypyrimidine (6.2 g, 50 mmol) and phosphorus oxychloride (46 g, 0.3 mol) was heated at reflux for 3 hours. The resulting coloured solution was cooled and then poured onto a mixture of crushed ice and sodium hydrogen carbonate (170 g) and allowed to warm to room

temperature with stirring. Extraction with trichloromethane (three times) followed by drying of the extracts and evaporation in vacuo gave 7.2 g crude 4-chloro-2,6-dimethylpyrimidine as a yellow oil which was used in the next step without further purification.

(ii) Preparation of 2,6-dimethyl-4-(prop-2-enyl)- aminopyrimidine

The 4-chloro-2,6-dimethylpyrimidine (5.6 g, 39 mmol) obtained in (i) above was heated at reflux for 5 hours in prop-2-enylamine (40 ml). Excess amine was then evaporated and the residue partitioned between trichloromethane and water. Drying (MgSO ) and evaporation in vacuo gave 5.3 g 2,6-dimethyl-4- (prop-2-enyl)amino- pyrimidine as a yellow oil.

(iii) Preparation of 2,6-dimethyl-4-(2,3-dihydroxypropyl)- aminopyrimidine

A mixture of the 2,6-dimethyl-4-(prop-2-enyl)aminopyrimidine (5.2 g, 31.9 mmol) obtained in (ii) above, N-methylmorpholine N-oxide (4.52 g, 33.5 mmol) and a catalytic amount of osmium tetroxide in acetone (25 ml) and water (25 ml) was stirred for 4 hours at 50°C. The reaction was then quenched with saturated aqueous sodium hydrogen sulphite solution (3 ml) and evaporated in vacuo. The residue was taken up in ethanol and "HYFLO" (Trade Mark: diatomaceous earth) and potassium carbonate were added and the mixture well stirred. Filtration and evaporation yielded a yellow oil which was purified by filtering through silica gel using 4:1 toluene: ethanol as eluant. This yielded a faintly yellow oil which crystallised upon standing to give 3.7 g 2,6-dimethyl-4-(2,3-dihydroxypropyl)aminopyrimidine, m.pt. 144-146°C.

(iv) Preparation of 8-(1,1-dimethyIpropyl)-2-[(2,6-dimethyl- pyrimidin-4-ylamino)methyl]-1,4-dioxaspiro [4.5] decane

A suspension of the 2,6-dimethyl-4-(2,3-dihydroxypropyl)-aminopyrimidine (1.08 g, 5.5 mmol) obtained in (iii) above, 4- (1, 1-dimethypropyl) cyclohexanone (0.84 g, 5.0 mmol) and paratoluenesulphonic acid (1.15 g, 6.0 mmol) in trichloromethane (50 ml) was heated at reflux with the condensate being passed through 4 x 10 m molecular sieves. After 5 hours, the reacton mixture was washed with aqueous sodium carbonate solution and dried (MgSO₄). Evaporation in vacuo yielded 1.5 g 8-(1,1-dimethyIpropyl)-2-[(2,6-dimethylpyrimidin-4-ylamino)methyl]-1,4-dioxaspiro-[4.5]decane as a colourless oil, m/e (M ): 347.

Analysis

Calc. C: 69.1; H : 9 . 6; N : 12 . 1%

Found C: 68.4; H : 9 . 9; N: 12 .4%

Examples 2 to 80

By processes similar to those described in Example 1 above, further compounds according to the invention were prepared as detailed in Tables I, II and III below. In these tables the compounds are identified by reference to formula I. Melting point, mass spectroscopy (m/e) and C,H,N analysis data for the compounds of Examples 2 to 80 are given in Tables IA,

IIA and IIIA below. TABLE I

(N.B. In all the following examples n-1 and R⁵ - R⁶- R⁹- H) Ex. R¹ R² R³ R⁴ R⁷ R⁸ R¹¹ R¹¹

No.

2 -CH₃ -CH₃ -H -H -H -H 3-C(CH₃)₃ pentamethylene

3 -CH₃ -CH₃ -H -H -H -H 3-C(CH₃)₂cyclohexyl pentamethylene

4 -CH₃ -CH₃ -H -H -H -H pentamethylene

5 -CH₃ -CH₃ -H -H -H -H heptamethylene

6 -CH(CH₃)₂ -CH₃ -H -H -H -H 3-C(CH₃)₃ pentamethylene

7 -CH(CH₃)₂ -CH₃ -H -H -H -H 3-C(CH₃)₂CH₂CH₃ pentamethylene 8 -CH(CH₃)₂ -CH₃ -H -H -H -H 3-C(CH₃)₂cyclohexyl pentamethylene 9 -H -CH₃ -CH₃ -H -H -H 3-C(CH₃)₃ pentamethylene

10 -CH₃ -CH₃ -H -H -H -H -ⁿC₃H₁₁ -H

11 -CH₃ -CH₃ -H -H -H -H -ⁿC₃ H₉ -CH₃

12 -CH₃ -CH₃ -H -H -H -H -ⁿC₃H₃ -C₂H₅

13 -CH₃ -CH₃ -H -H -H -H 3-phenylpentamethylene

14 -CH₃ -CH₃ -H -H -H -H phenyl -CH₃

15 -CH-CH-C₆H₅ -CH₃ -H -H -H -H -H phenyl

TABLE I (continued)

Ex. R¹ R² R³ R⁴ R⁷ R⁸ R¹⁰ R¹¹

No.

16 -H -C₂H₅ Cl -H -H -H pentamethylene

17 -H -C₂H₅ Cl - H -H -H 3-C(CH₃)₃ pentamethylene

18 -H -C₂H₅ Cl -H -H -H 3-C(CH₃)₂CH₂CH₃ pentamethylene 19 -H -C₂H₅ Cl - H -H -H -CH₃ -ⁿC₃H₉

20 -H -C₂H₅ Cl -H -H -H -C₂H₅ -ⁿC₃H₇

21 -H -C₂H₅ Cl -H -H -H phenyl -H

22 -CH ₃ -CH ₃ H -H -H -H -H phenyl

23 -H -C₂H₅ Cl - H -H -H -H -ⁿC₃H₁₁

24 -H -C₂H₅ Cl - H -H -H -CH ₃ phenyl

25 -H -C₂H₅ Cl - H -H -H 3-phenylpentamethylene

26 -H -C₂H₅ H - H -H -H phenyl -H

27 -H -C₂H₅ H - H -H -H 4-C(CH₃)₃ phenyl -H

28 -H -C₂H₅ H - H -H -H -CH ₃ 4-C(CH₃)₃ phenyl 29 -H -C₂H₅ H -H -H -H phenyl -CH₃

30 -H -C₂H₅ H -H -H -H 3-phenylpentamethylene

TABLE I (continued)

Ex. R¹ R² R³ R⁴ R⁷ R⁸ R¹⁰ R¹¹

No.

31 -H -C₂H₅ -H -H -H -H 3-C(CH₃)₃ pentamethylene

32 -H -C₂H₅ -H -H -H -H 3-C(CH₃)₂CH₂CH ₃ pentamethylene 33 -CH -C₂H₅ -H -H -H -H 3-C(CH₃)₃ pentamethylene

34 -CH -C₂H₅ -H -H -H -H 3-C(CH₃)₂CH₂CH ₃ pentamethylene 35 -CH -C₂H₅ -H -H -H -H 3-phenylρentamethylene

36 -CH -C₂H₅ -H -H -H -H phenyl -H

37 -CH ₃ -C₂H₅ -H -H -H -H phenyl -CH₃

38 -CH -C₂H₅ -H -H -H -H 4-C(CH₃)₃ phenyl -CH₃

39 -CH ₃ -C₂H₅ -H -H -H -H 4-C(CH₃)₃ phenyl -H

40 -CH -CH₃ -H -H -H -H -CH ₃ 4-C(CH₃)₃ phenyl 41 -CH -CH₃ -H -H -H -H -H 4-C(CH₃)₃ phenyl 42 -H -CH₃ -H -H -H -H 3-C(CH₃)₃ pentamethylene

43 -H -CH₃ -CH ₃ -H -H -H 4-C(CH₃)₃ phenyl -H

44 -H -CH ₃ -CH ₃ -H -H -H 3-C(CH₃) CH CH ₃ pentamethylene 45 -H -CH ₃ -CH ₃ -H -H -H 4-C(CH₃)₃ phenyl -CH₃

TABLE I (continued)

Ex. R¹ R² R³ R⁴ R⁷ R⁸ R¹⁰ R¹¹ No.

46 -CH₃ -CH₃ -H -CH₃ -H -H 4-C(CH₃)₃ phenyl -H 47 -CH₃ -CH₃ -H -CH₃ -H -H 4-C(CH₃)₃ phenyl -CH₃ 48 -CH₃ -CH₃ -H -CH₃ -H -H 3-C(CH₃)₃ pentamethylene

49 -CH₃ -CH₃ -H -CH₃ -H -H 3-C(CH₃)₂CH₂CH₃ pentamethylene 50 -CH₃ -CH₃ -H -H -CH₃ -H 3-C(CH₃)₃ pentamethylene

51 -CH₃ -CH -H -H -CH₃ -H 3-C(CH₃)₂CH₂CH₃ pentamethylene 52 -CH₃ -CH₃ -H -H -CH₃ -H 4-C(CH₃)₃ phenyl -CH₃ 53 -CH₃ -CH₃ -H -H -H -CH 4-C(CH₃)₃ phenyl -H 56 -CH₃ -CH₃ -H -H -H -CH 4-C(CH₃)₃ phenyl -CH₃ 55 -CH₃ -CH₃ -H -H -H -CH 3-C(CH₃)₃ pentamethylene

56 -CH₃ -CH₃ -H -H -H -CH 3-C(CH₃)₂CH₂CH₃ pentamethylene 57 -CH₃ -Cl -H -H -H -H 3-C(CH₃)₃ pentamethylene

58 -CH₃ -OCH -H -H -H -H 3-C(CH₃)₃ pentamethylene

59 -H -C₂H₅ -Cl -H -H -H 4-C(CH₃)₃ phenyl H 60 -CH -CH₃ -H -H -H -H 2,2,6-(CH₃)₃ cyclohexylethyl CH₃ 61 -CH₃ -OC₂H₅ -H -H -H -H 3-C(CH₃)₃ pentamethylene

TABLE I (continued)

Ex. R¹ R² R³ R⁴ R⁷ R⁸ R¹⁰ R¹¹

No.

62 -CH₃ O C₃H₇ -H -H -H -H 3-C(CH₃)₃ pentamethylene

63 -CH₃ OCH(CH₃)C₂H₅ -H -H -H -H 3-C(CH₃)₃ pentamethylene

64 -CH₃ 0CH(CH₃)₂ -H -H -H -H 3-C(CH₃)₃ pentamethylene

65 -CH₃ NHCH₃ -H -H -H -H 3-C(CH₃)₃ pentamethylene

66 -CH₃ N(CH₃)₂ -H -H -H -H 3-C(CH₃)₃ pentamethylene

67 -CH NHC₆H₅ -H -H -H -H 3-C(CH₃)₃ pentamethylene

68 -CH N(CH₃)ⁿC₆H₁₃ -H -H -H -H 3-C(CH₃)₃ pentamethylene

69 -CH CH₃ -H -H -H -H benzyl -CH₃

70 -CH CH₃ -H -H -H -H phenethyl -CH₃

71 -CH CH₃ -H -H -H -H 2-CH(CH₃)₂ pentamethylene

72 -CH CH₃ -H -H -H -H 2,3-tetramethylene-peetamethylene 73 -CH₃ CH₃ -H -H -H -H 3-CH(CH₃)₂ pentamethylene

TABLE I ( continued)

Ex . R¹ R² R³ R⁴ R⁷ R⁸ R¹⁰ R¹¹

No .

81 Cl CH₃ 3-C(CH₃)₃pentamethylene 82 0CH₃ CH3 3-C(CH₃)₃pentamethylene 83 OC₂H₅ CH₃ H H H H 3-C(CH₃)₃pentamethylene 84 OC₃H₇ CH₃ H H H H 3-C(CH₃)₃pentamethylene 85 OCH(CH₃)₂ CH₃ H H H H 3-C(CH₃)₃pentamethylene 86 OCH(CH₃)CH₂CH₃ CH₃ H H H H 3-C(CH₃)₃pentamethylene 87 OCH₂CH(CH₃)₂ CH₃ H H H H 3-C(CH₃)₃pentamethylene 88 CH₃ OCH₂CH(CH₃)₂ H H H H 3-C(CH₃)₃pentamethylene 89 CH₃ OCH₂CH(CH₃)₂ H H H H 3-C(CH₃)₃pentamethylene 90 NHC₆H₅ CH₃ H H H H 3-C(CH₃)₃pentamethylene 91 N(CH₃)₂ CH₃ H H H H 3-C(CH₃)₃pentamethylene 92 NHCH₃ CH₃ H H H H 3-C(CH₃)₃pentamethylene 93 NCH₃(C₆H₁₃) CH₃ H H H H 3-C (CH₃)₃pentamethylene 94 H C₂H₅ Cl H H H 4-Cl-C₆H₅ H

95 H C₂H₅ Cl H H H 4-CH₃-C₆H₅ H

96 H C₂H₅ Cl H H H 4-F- C₆H₅ H

97 H C₂H₅ Cl H H H 3-Cl-C₆H₅ H

TABLE IA m/e Analysis (%)

Ex. M.pt. M+ C H C

No. (°C) (Diastereomer ratio) Calc. Found Calc. Found Calc. Found

2 333 (1:1)

3 401 (1:1)

4 76-79 277 (1:1)

5 80-83 305 (1:1)

6 361 (1:1.5)

7 375 (1:1.5)

8 429 (1:1)

9 333 (1:1)

10 279 (1:1) 64.49 64.08 9.02 9.26 15.04 14.51 11 279 (1:1) 64.49 63.71 9.02 8.98 15.04 14.54 12 279 (1:1) 64.49 63.74 9.02 8.59 15.04 14.58 13 353 (1:1) 71.36 69.93 7.70 7.78 11.82 10.58 14 299 (1:1.4)

15

16 311 (1 isomer) 57.78 54.77 7.11 6.63 13.48 12.13 17 367 (1:1) 62.03 61.24 8.22 8.28 11.42 11.09

TABLE IA (continued) m/e Analysis (%)

Ex. M.pt. M+ C H N

No. (°C) (Diastereomer ratio) Calc. Found Calc. Found Calc. Found

18 381 (1:1) 62.89 61.56 8.44 9.66 11.00 10.07

19 313 (1:1.7) 57.41 57.16 7.71 7.44 13.39 13.12

20 313 (1:1) 57.41 57.42 7.71 7.86 13.39 13.46

21 60.10 57.58 5.67 6.25 13.14 12.09

22 285 (not determined) 67.35 63.99 6.71 7.72 14.73 13.24

23 313 (1:1) 57.41 57.52 7.71 7.84 13.39 13.35

24 333 (1:2) 61.17 61.39 6.04 6.33 12.59 12.48

25 387 (1:1) 65.02 61.63 6.76 6.70 10.83 9.91

26 285 (1:1.7) 67.35 63.49 6.71 6.31 14.73 13.44

27 341 (1 isomer) 70.35 66.85 7.97 6.28 12.31 10.66

28 355 (1:2)

29 299 (1:2) 68.20 66.45 7.07 6.66 14.04 12.77 30 353 (1:1)

31 333 (1:1.6)

32 347 (1:1.7) 69.13 67.37 9.57 9.64 12.09 10.73

33 347 (1:1)

34 361 (1:1)

TABLE IA (continued) m/e Analysis (%)

Ex. M.pt. M+ C H N

No. (°C) (Diastereomer ratio) Calc. Found Calc. Found Calc. Found

35 367 (1:1)

36 299 (1:1) 68.20 66.79 7.07 6.85 14.04 13.30 37 313 (1:1.5)

38 369 (1:2)

39 355 (1:3) 70.96 67.98 8.22 7.93 11.82 11.00 40 355 (1:2)

41 70.35 67.19 7.97 7.53 12.31 12.09 42 319 (3:2)

43 361 (1 isomer)

44 74-84 347 (1:1)

45 355 (2:1)

46 355 (1:1) 70.96 70,28 8.22 7.58 11.82 11.16 47 369 (1 isomer) 71.51 70.86 8.46 8.30 11.37 10,70 48 347 (1:1) 69.13 65.11 9.57 8.73 12.09 11.17 49 361 (1:1) 69.77 68.55 9.76 9.15 11.62 11.15 50 347 (1:2) 69.13 66.39 9.57 8.75 12.09 10.79 51 361 (1:1.6) 69.77 68.96 9.76 8.12 11.62 11.51

TABLE IA (continued) m/e Analysis (%)

Ex. M.pt. M+ C H N

No. (°C) (Diastereomer ratio) Calc. Found Calc. Found Calc. Found

52 369 (1:3) 71.53 69.38 8.46 9.21 11.37 10.34 53 355 (1:1) 70.96 69.00 8.22 8.84 11.82 11.34 54 369 (1:1. 6)

55 347 (1:1) 69.13 65.44 9.57 8.72 12.0? 10.96 56 361 (1:1) 69.77 66.68 9.76 7.55 11.62 10.89 57 353 (1:1) 61.09 60.96 7.97 8.01 11.87 11.38 58 349 (1:1) 65.30 62.14 8.94 8.00 12.02 10.56 59 375 (1:2. 5) 63.91 63.55 6.97 6.94 11.18 11.42 60 375 (1:1) 70.35 69.81 9.93 9.35 11.19 10.46 61 363 (1:1) 66.09 66.15 9.15 8.79 11.56 10.08 62 377 (1:1) 66.81 66.51 9.34 9.22 11.13 10.07 63 391 (1:1) 67.49 67.25 9.52 9.66 10.73 9.99 64 377 (1:1) 66.82 66.66 9.35 9.28 11.13 10.28 65 125-127 348 (1:1) 65.48 65.13 9.26 8.97 16.08 15.29 66 362 (1:1) 66.26 64.48 9.45 9.16 15.45 14.46 67 410 (not determined) 70.21 68.20 8.35 8.12 13.65 12.79 68 432 (1:1) 69.40 66.08 10.25 9.38 12.95 12.11

TABLE IA ( continued) m/e Analysis (%)

Ex. M.pt. M+ C H N

No. (°C) (Diastereomer ratio) Calc. Found Calc. Found Calc. Found

69 313 (1:1) 68.99 67.93 7.40 7.11 13.41 12.84

70 327 (1::1) 69.70 68.71 7.70 7.59 12.83 12.48

71 319 (1: : 1:2:2) 67.68 65.75 9.15 8.80 13.15 12.08

72 331 (1 .1:1.5:9:4:4) 68.85 64.71 8.82 8,24 12.68 11.09

73 319 (1 :1) 67.68 66.56 9.15 8.55 13.15 12.15

TABLE IA (continued) m/e Analysis (%)

Ex. M.pt. M+ C H C No. (°C) (Diastereomer ratio) Calc. Found Calc. Found Calc. Found 81 353 (1:1.4) 61.09 61.11 7.97 7.81 11.87 10.7

82 128-130 349 (1:1.6) 65.3 65.05 8.94 8.75 12.02 11.77

83 363 (1:1.5) 66.09 63.97 9.15 9.09 11.56 10.57

84 377 (1:1.6) 66.83 63.77 9.35 9.1 11.13 9.57

85 377 (1:1.6)

86 391 (1:1.4)

87 391 (1:1.6) 67.48 64.39 9.52 9.3 10.73 8.5

88 391 (1:14.0)

89 391 (10:0.1)

90 410 (not determined) 70.21 69.98 8.35 7.8 13.65 13.09

91 362 (not determined) 66.27 64.07 9.45 9.05 15.46 12.93

92 348 (1:1)

93 333 (not determined)

94 354 (1:1) 54.26 55.77 4.84 5.47 11.86 10.31

95 333 (1:1) 61.17 61.49 6.04 6.27 12.59 11.36

96 337 (1:1) 54.26 57.2 4.84 5.81 11.86 10.82

97 354 (1:1) 54.26 55.36 4.84 5.4 11.86 10.67

TABLE II

(N.B. In all the following examples n-1, R⁵-CH₃ and R⁶-R⁹-H) Ex. R¹ R² R³ R⁴ R⁷ R⁸ R¹⁰ R¹¹

No.

74 -CH₃ -CH₃ -H -H -H -H 4-C(CH₃)₃phenyl -H

75 -CH₃ -CH₃ -H -H -H -H 4-C(CH₃)₃phenyl -CH₃

76 -CH₃ -CH₃ -H -H -H -H 3-C(CH₃)₃ pentamethylene 77 -CH₃ -CH₃ -H -H -H -H 3-C(CH₃)₃CH₂CH₃ pentamethylene

TABLE III

(N.B. In all the following examples n-2, R⁵-R⁶-R⁹-H) Ex. R¹ R² R³ R⁴ R⁷ R⁸ R¹⁰ R¹¹

No.

78 -CH₃ -CH₃ -H -H -H -H 3-C(CH₃)₃ pentamethylene 79 -CH₃ -CH₃ -H -H -H -H 3-C(CH₃)₃CH CH pentamethylene 80 -CH₃ -CH₃ -H -H -H -H 4-C(CH₃)₃phenyl -H

TABLE IIA

Analysis (%)

Ex. m/e C H N

No. M+ (Diastereomer ratio) Calc. Found Calc. Found Calc. Found

74 355 (2.5:1.8:2:1) 70.96 68.58 8.22 7.61 11.82 11.17 75 369 (1.5:1:3.5:2.3) 71.51 68.22 8.46 7.66 11.37 10.39 76 367 (1.5:1:2.6:1) 69.13 66.90 9.57 9.06 12.09 11.52 77 361 (1.5:1:2.5:1) 69.77 67.86 9.76 9.38 11.62 10.20

TABLE IIIA

Analysis (%)

Ex. m/e C H N

No. MH (Diastereomer ratio) Calc. Found Calc. Found Calc. Found

78 367 (1:1) 69.13 65.84 9.57 9.09 12.09 11.04 79 361 (1:1) 69.77 67.36 9.76 8.99 11.62 10.81 80 355 (1:1.5) 70.96 65.10 8.22 7.52 11.82 10.64

Example 98

The fungicidal activity of compounds of the invention was investigated by means of the following tests and those of

Example 101.

(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 × 10⁴ 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 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 × 10⁴ 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.

(c) Activity against wheat leafspot (Leptosphaeria nodorum;

LN.)

The test is a direct therapeutic one using a foliar spray. Wheat seedlings (cv Norman), at the single leaf stage, are inoculated with an aqueous suspension containing 1.5 × 10⁶ conidia/ml. The inoculated plants are kept for 24 hours at 20 °C in a high humidity cabinet followed by spraying with the test compound at a dosage of 600 ppm as described under (a). After drying, the plants are kept for 6-8 days in a glasshouse at 22 ºC and 70% relative humidity. Assessment is based on the density of lesions per leaf compared with that on leaves of control plants.

(d) Activity against barley powder mildew (Erysiphe graminis f.sp. hordei: EGT)

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.

(e) 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.

(f) Direct protectant activity against tomato late blight

( Phytophthora 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 10⁵ 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.

(g) Activity against wheat eyespot in-vitro

(Pseudocercosporella herpotrichoides; PHI)

This test measures the in vitro activity of compounds against 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 0.825% 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 × 10⁴ mycelial fragments/ml broth. Petri dishes are incubated at 20°C for 10 days until the assessment of mycelial growth.

(h) 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 provide 5 × 10⁴ fragments/ml broth. Petri dishes are incubated at 20°C for 10 days until the assessment of mycelial growth. (i) 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 10ppm 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 × 10⁴ propagules/ml broth. Petri dishes are incubated at 20°C for 10 days until the assessment of mycelial growth.

(j) Activity against rice leaf blast (Pyricularia oryzae; PO)

The test is a direct therapeutic one using a foliar spray. The leaves of rice seedlings (cv Aichiaishi - about 30

seedlings per pot) are sprayed with an aqueous suspension containing 10⁵ spores/ml 20-24 hours prior to treatment with the test compound. The inoculated plants are kept overnight in high humidity and then allowed to dry before spraying with the test compound at a dosage of 1000 ppm using an automated sprayline as described under (a). After treatment the plants are kept in a rice compartment at 25-30°C and high humidity. Assessments are made 4-5 days after treatment and are based on the density of necrotic lesions per leaf when compared with control plants.

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:-

0 = 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 IV below:- TABLE IV

Example Fungicidal Activity

No. AS BCB LN EGT EGP PIP PHI RSI VII PO

1 2 2 2 2 1 2

2 2 2 1 2 2 2

3 2 2 2 2 2 2 1

4 1

5 2 1 2

6 2 2 1 2 2 2 1 1

7 2 2 1 2 2 2 1

8 1 2 2 2 2 2 2 2

9 1 2 2 2 2 1

10 2 1

11 2 2 2

12 2 2

13 2 2 2

14 1 2

15 1

16 2 2

17 2 2 1

18 2 1 1

19 2 2 2

20 2 2 2 1

21 2 2 2

22 2

23 2 1

24 1 2 2 2 1

25 1 2 2 2 1 1 1

26 1 1 1

27 2 2

28 1 2

29 2 TABLE IV (continued)

Example Fungicidal Activity

No. AS BCB LN EGT EGP PIP PHI RSI VII PO

30 2 2 1

31 1 2 2 1 1

32 1 2 2 2

33 2 2 2 2

34 2 2 1 2 2 2

35 2 2 1

36 1 1 1

37 1 1

38 2 2 2 1

39 2 2 1

40 1 1 2 1

41 1 1 2 1

42 2 2 2 1 1

43 1 1 2 2

44 2 1 2 2 2

45 2 2 2

46 1 1 2

47 1 2 2

48 1 2 2 2 2 2

49 2 2 2 2 2

50 1 1 2 2 2

51 1 2 1 2 2 2

52 2 2

53 2

54 2

55 1 1 1 1

56 1 2 1

57 2 2 1

58 2 2 1

59 2 2 TABLE IV (continued)

Example Fungicidal Activity

No. AS BCB LN EGT EGP PIP PHI RSI VII PO

60 1

61 1 2 1

62 1 2 1 1

63 1 1 1 1 1 64 1 2 1 1

65 1 1 2 2

66 1 1 2 1 2

67 1 1 2

68 1 1 2 2 69 1 1 1

70 1

71 2 1 2 1

72 1

73 1 2 2

74 1

75 1

76 2 2 1 2

77 1 2 2 1 1 2

78 1 2 2 1 79 2 2 2 1

80 2

Example 99

The insecticidal activity of compounds of the invention was assessed against the following pests:-

Musca domestica (housefly)

Acyrthosiphon pisum (pea aphid)

Plutella xylostella (diamond-back moth)

The test methods employed for each species appear below. In each test, unless otherwise stated, solutions or suspensions of test compound were made up over a range of concentrations in water (initially 0.1%w) containing 10%w acetone and 0.025%w "TRITON X-100" (trade mark) surface active agent (the condensation product of ethylene oxide with an alkyl phenol). These solutions were sprayed at a rate equivalent to

340 litres per hectare (3.4 × 10^-5m³/m²) onto Petri dishes containing either test species per se or diet onto which test species were subsequently introduced, as indicated. In some assays leaf discs infested with test species were sprayed whilst other assays involved the spraying of plants which were infested subsequently with test species after the spray solution had dried. The tests were all conducted under normal insectary conditions (23°C + 2°C, fluctuating humidity and light).

Mortality assessments were made as indicated below, in terms of percentage mortality figures. In each test a LC₅₀ (the dosage of active material required to kill half of the test species) for the compound was calculated from the mortality figures and compared with the corresponding LC₅₀ for a standard insecticide, ethyl parathion, in the same test. The results are expressed as toxicity indices thus:

(i) Musca domestica (Md)

Batches of ten 2 to 3 day old milk-fed adult female houseflies, anaesthetised using carbon dioxide, were placed on filter papers inside Petri dishes. The dishes were sprayed with the test solutions as described above. The flies were retained in the Petri dishes and were fed with a dilute milk solution which was dripped down the side of the Petri dish and absorbed by the filter paper. Mortality was assessed after 24 hours. (ii) Acyrthosiphon pisum (Ap)

Tests were carried out on young adult pea aphids.

Whole pea plants 6 days after germination were placed on filter papers in Petri dishes. Ten aphids were transferred to each pea plant and left for 30 minutes to allow the aphids to settle and start to feed. The dishes were then sprayed with the test solutions as described above and lids were placed on the Petri dishes. Mortality was assessed after 24 hours,

(iii) Plutella xylostella (Px)

Test solutions were sprayed as described above onto Petri dishes containing 5 cm discs of Chinese cabbage leaves on filter papers. After drying, each dish was infested with ten 3rd instar diamond-back moth larvae. Mortality assessments were made 48 hours after infestation. TABLE V

Example No. Toxicity index

M.d. A.p. P.x. 16 2 19

17 2 <11

18 4 39

19 7 <14

20 5

21 7 28

23 1 13 16

24 13

25 9 38 Example 100

The acaricidal activity of the compounds of the invention was determined in the following tests employing the glasshouse red spider mite, Tetranychus urticae (T.u.).

In each test solutions or suspensions of test compound were made up over a range of concentrations in water (initially

0.1%w) containing 10%w acetone and 0.025%w "TRITON X-100" (trade mark) surface active agent (the condensation product of ethylene oxide with an alkyl phenol). These solutions were sprayed at a rate equivalent to 340 litres per hectare (3.4 × 10 -5m3/m2) onto petri dishes containing either test species per se or diet onto which test species were subsequently introduced, as indicated.

The tests were all conducted under normal insectary conditions (23°C ± 2°C, fluctuating humidity and 16 hours day length light).

Mortality assessments were made as indicated below, in terms of percentage mortality figures. In each test a LC₅₀ (the dosage of active material required to kill half of the test species) for the compound was calculated from the mortality figures and compared with the corresponding LC₅₀ for a standard insecticide (either ethyl parathion or chlorfenson, as

indicated) in the same test. The results are expressed as toxicity indices thus:

(i) Acaricidal activity - mite adults Tu

Acaricidal activity was assessed using adult glasshouse red spider mites, Tetranychus urticae (T.u.), 7-10 days after hatching, by the following procedure:

2 cm diameter discs cut from the leaves of French bean plants were placed on filter paper kept moist by a cotton wool wick dipped into water. Prior to testing, each leaf disc was infested with 10 adult mites. The mites and discs were then sprayed with solutions of the test compound made up as above, at a rate equivalent to 340 litres per hectare (3.4 × 10 5 m³/m²).

The mites were held under the normal insectary conditions. The numbers of dead and moribund adults were assessed after 48 hours and the percentage mortality calculated.

(ii) Acaricidal activity - ovicide TuOA

Acaricidal activity was assessed employing eggs of the glasshouse red spider mite, Tetranychus urticae (T.u.), less than 24 hours old, by the following procedure.

2 cm diameter leaf discs cut from the leaves of French bean plants were placed on filter paper, kept moist by a cotton wool wick dipped into water.

On the day before spraying, each leaf disc was infested with 10 female adult mites. On the day of the test, the adults were removed, leaving the eggs laid overnight on the discs. The leaf discs were then sprayed with solutions of test compound made up as above, at a rate equivalent to 340 litres per hectare (3.4 × 10^-5 m³ /m²).

Throughout the test, the eggs were held under the normal insectary conditions. After 7-10 days, the numbers of hatched nymphs and unhatched eggs were assessed and the percentage mortality calculated.

The LC₅₀ (the dosage of active material required to kill half of the test species) for each test compound was calculated from the mortality figure and compared with the corresponding LC₅₀ for a standard insecticide in the same test.

For Tu ethyl parathion was used as the standard compound; for TuOA chlorfenson was used as the standard.

The results are given in Table VI below.

TABLE VI

Example No. Toxicity Index

Tu Tu OA

16 4 47

17 10 34

18 7

19 3 74

20 5 < 16

21 11 71

23 7 130

24 11 160 25 24 210

27 < 16

30 <1 15

The compound of Example 17 also demonstrated nematocidal activity in a soil drench test. Example 101

The fungicidal activity of compounds of the invention was investigated by means of the following tests and those of Ex. 98.

(a) Evaluation of in vivo fungicidal activity of test compounds

Test compounds were dissolved or suspended in acetone and diluted with deionized water containing about 0.05% TWEEN^®20, a polyoxyethylene sorbitan monolaurate surfactant manufactured by Atlas Chemical Industries, to give a concentration of 200 ppm.

Host plants were sprayed with the test solution, dried and inoculated with fungi. When disease symptom development was optimal, the plants were rated for disease control according to the rating scale shown below. Each test contained inoculated treated plants, inoculated untreated plants and a reference standard. When more than one test was run, the data were averaged. The data obtained are shown in Table VII.

RATING SCALE

Rating Range % Disease Control

0 0

1 1-14

2 15-29

3 30-44

4 45-59

5 60-74

6 75-89

7 90-95

8 96-99

9 100 PHYTOPATHOGENIC FUNGI

Symbol Disease Pathogen

VII Apple Scab Venturia inaequalis

GDM Grape Downy Mildew Plasmopara viticola

PB Pepper Botrytis Botrytis cinerea

RB Rice Blast Pyricularia grisea

SBC Sugar Beet Cercospora Cercospora beticola

TEB Tomato Early Blight Alternaria solani

WPM Wheat Powdery Mildew Erysiphe graminis

f . sp. tritici

WSN Wheat Septoria Nodorum Septoria nodorum

Table VII

Ex. Rate In Vivo Fungicidal Activity

No. (ppm VII GDM PB RB SBC TEB WPM WSN

81 200 0.0 0.0 0.0 0.0 3.0 2.0 0.0 0.0

82 200 0.0 0.0 8.5 0.0 0.0 6.5 4.0 0.0

83 200 0.0 5.0 5.0 0.0 4.0 6.0 7.0 0.0

84 200 0.0 0.0 0.0 0.0 0.0 2.0 3.0 0.0

85 200 3.0 3.0 3.0 0.0 5.0 5.0 4.0 0.0

86 200 0.0 0.0 0.0 0.0 0.0 3.0 0.0 0.0

87 200 0.0 0.0 0.0 0.0 0.0 0.0 3.0 0.0

88 200 0.0 0.0 0.0 0.0 0.0 0.0 8.0 0.0

89 200 3.0 0.0 0.0 0.0 0.0 0.0 3.0 0.0

90 200 5.0 5.0 8.5 0.0 3.0 0.0 0.0 0.0

91 200 0.0 0.0 5.0 0.0 0.0 7.0 7.0 5.0

92 200 4.0 5.0 0.0 0.0 5.0 5.0 6.0 7.0

93 200 3.0 0.0 8.5 0.0 0.0 0.0 3.0 0.0

94 200 8.5 6.0 0.0 0.0 0.0 0.0 7.0 0.0

95 200 7.0 0.0 0.0 0.0 0.0 0.0 7.0 0.0

96 200 7.5 4.0 0.0 0.0 0.0 0.0 7.0 0.0

97 200 7.5 8.0 0.0 3.0 4.0 0.0 5.0 0.0 (b) Evaluation of the in vitro fungicidal activity of compounds of the invention

Test compounds were dissolved or suspended in acetone and dispersed into cell well plates containing a suspension of ground fungal mycelia/spores in a nutrient broth. Assay plates were incubated for 3-7 days at 21°C. Growth inhibition was measured visually and was rated using the following scale:

Rating % Growth Inhibition

0 0

1 1-29

3 30-59

5 60-89

7 90-99

9 100

PLANT PATHOGENS

Abbreviation Scientific Name

PYTHUL Pythium ultimum

RHIZSO Rhizoctonia solani

FUSOXC Fusarium oxysporum f.sp. cucumerinum PSDCHE Pseudocercosporella herpotrichoides

When more than one test was run the data were averaged. The data obtained are shown in Table VIII.

Table VIII

In Vitro Fungicidal Activity

Ex. Rate

No. (ppm) FUSOXC PYTHUL RHIZSO PSDCHE

81 25 0.0 0.0 3.0 3.0

82 25 0.0 0.0 8.0 6.0

83 25 0.0 0.0 8.0 6.0

84 25 0.0 0.0 8.0 2.5

85 25 0.0 3.5 8.0 6.0

86 25 0.0 0.0 8.0 0.5

87 25 0.0 0.0 8.0 3.0

88 25 0.0 0.0 1.0 5.0

89 25 0.0 0.0 1.0 5.0

90 25 0.0 2.0 8.0 7.0

91 25 0.0 7.0 8.0 7.0

92 25 0.0 0.0 8.0 6.0

93 25 5.0 7.0 8.0 7.0

94 25 0.0 0.0 7.0 4.0

95 25 0.0 0.0 3.0 0.0

96 25 0.0 0.0 3.0 0.0

97 25 0.0 0.0 6.0 5.0

Claims

C L A I M S

1. A compound of the general formula

in which

R¹, R² and R³ independently represent a hydrogen or halogen atom, nitro, cyano, hydroxyl, carboxyl or optionally substituted alkyl, alkenyl, alkynyl, alkoxy, amino, alkoxycarbonyl, alkanoyl, cycloalkyl, alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, alkylamido or phenyl group;

n represents an integer from 1 to 3;

R⁴ R⁵, R⁶, R⁷, R⁸ and R⁹ independently represent a hydrogen atom or an optionally substituted alkyl group; and

R¹⁰ and R¹¹ independently represent a hydrogen atom or an optionally substituted alkyl or aryl group; or

R¹⁰ and R¹¹ together represent an optionally substituted alkylene or alkenylene chain;

with the proviso that R⁷, R⁸, R⁹, R¹⁰ and R¹¹ do not

simultaneously represent a hydrogen atom.

2. A compound according to claim 1 in which R ¹, R² and R³ independently represent a hydrogen or halogen atom or an amino, C_1-6 alkyl, C_2-6 alkenyl or C_1-6 alkoxy group, each group being optionally substituted by one or more substituents selected from halogen atoms, nitro, cyano, C_1-6 alkyl, C_1-6 haloalkyl, C_1-6 alkoxy, C_1-6 haloalkoxy, C_1-6 alkylamino, di-C_1-6 alkylamino, C _1-6 alkoxycarbonyl, carboxyl, C_1-6 alkanoyl, C_3-6 cycloalkyl and phenyl groups.

3. A compound according to claim 1 or claim 2 in which R⁴ represents a hydrogen atom or a C_1-6 alkyl group optionally substituted by one or more halogen atoms.

4. A compound according to any one of the preceding claims in which R⁵ and R⁶ independently represent a hydrogen atom or a C_1-4 alkyl group.

5. A compound according to any one of the preceding claims in which n is 1 or 2.

6. A compound according to any one of the preceding claims in which R⁷, R⁸ and R⁹ independently represent a hydrogen atom or a C_1-6 alkyl group optionally substituted by one or more halogen atoms.

7. A compound according to any one of the preceding claims in which R¹⁰ and R¹¹ independently represent a hydrogen atom or a C_1-8 alkyl or phenyl group or R¹⁰ and R¹¹ together represent a C_4-8 alkylene chain; each group or chain being optionally substituted by one or more substituents selected from halogen atoms, nitro, cyano, hydroxyl, C_1-6 alkyl, C_1-6

haloalkyl, C_1-6 alkoxy, C_1-6 haloalkoxy, amino, C_1-6 alkylamino, di-C_1-6 alkylamino, C_1-6 alkoxycarbonyl, carboxyl, C_1-6

alkanoyl, C_1-6 cycloalkyl, C_1-6 alkyl-substituted C_1-6

cycloalkyl, C_1-6 cycloalkyl-C_1-6 alkyl and phenyl groups, or, in the case where R¹⁰ and R¹¹ together represent a C_4-8 alkylene chain, optionally substituted by a C_3-5 alkylene chain.

8. A compound according to any one of the preceding claims in which R¹ represents a hydrogen atom or a methyl, propyl or styryl group; R² represents a chlorine atom or a methyl, ethyl, methoxy, ethoxy, propoxy, butoxy, methylamino, dimethylammo, phenylamino or methyl-hexylamino group; R³ represents a hydrogen or chlorine atom or a methyl group; R⁴, R⁵, R⁷, R⁸ and R⁹ independently represent a hydrogen atom or a methyl group; n is 1 or 2; R⁶ represents a hydrogen atom; R¹⁰ and R¹¹ independently represent a hydrogen atom or a methyl, ethyl, propyl, butyl, pentyl, trimethylcyclohexyl- ethyl, phenyl, butylphenyl, benzyl or phenethyl group or R¹⁰ and R¹¹ together represent a pentamethylene, propylpentamethylene, butylpentamethylene, pentylpentamethylene,

cyclohexylpropylpentamethylene, phenylpentamethylene,

tetramethylene-pentamethylene or heptamethylene chain.

9. A compound according to claim 1 as named in any one of Examples 1 to 80.

10. A process for the preparation of a compound of general formula I according to any one of the preceding claims which comprises reacting a compound of the general formula

in which n, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸ and R⁸ are as defined in any one of the preceding claims, with a compound of the general formula

11. A process according to claim 10 substantially as hereinbefore described and with reference to Example 1.

12. A compound of formula I whenever prepared by a process according to claim 10 or claim 11.

13. A biocidal composition which comprises a carrier and, as active ingredient, a compound of general formula I as defined in any one of claims 1 to 9 and 12.

14. A composition according to claim 13 which comprises at least two carriers, at least one of which is a surface-active agent.

15. A method of combating fungus and/or pests at a locus which comprises treating the locus with a compound of general formula I as defined in any one of claims 1 to 9 and 12 or with a composition as defined in claim 13 or claim 14.

16. Use as a biocide of a compound of general formula I as defined in any one of claims 1 to 9 and 12 or of a composition as defined in claim 13 or claim 14.