GB2025407A - Benzyloxime ethers and their use as pesticides - Google Patents

Abstract

This invention relates to benzyloxime ether derivatives. The invention provides benzyloxime ether derivatives of formula: <IMAGE> wherein R<1> is an optionally substituted aryl or alkyl group, R<2> is an optionally substituted cycloalkyl, alkyl or alkenyl group, and X<1> and X<2> are independently selected from fluorine, chlorine and bromine; in the form of its E isomer, its Z isomer or a mixture thereof, methods for their preparation, pesticidal compositions containing them, and methods of using them to combat pests. Benzyloxime ether derivatives of formula I exhibit acaricidal activity.

Description

SPECIFICATION Benzyloxime ethers and their use as pesticides The invention relates to benzyloxime ethers, to their preparation, and to their use as pesticides.

The invention provides a compound of the general formula

wherein R' represents an optionally substituted aryl or alkyl group, R2 represents an optionallysubstituted cycloalkyl, alkyl or alkenyl group, and X1 and X2 are independently selected from fluorine, chlorine and bromine; in the form of either its E isomer or its Z isomer or a mixture thereof.

An aryl group represented by R1 is preferably a napthyl group, or a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms and alkyl or alkoxy groups preferably having from 1 to 4 carbon atoms, for example fluorine, chlorine and bromine atoms and methyl, ethyl, t-butyl and methoxy groups.

An alkyl group represented by R1 may be straight-chain or branched and may, for example, be substituted by one or more of the same or different substituents selected from halogen atoms, alkoxy groups and aryl groups, for example chlorine, fluorine and bromine atoms and methoxy and phenyl groups. The alkyl moiety preferably contains from 1 to 10 carbon atoms.

Conveniently R1 is a naphthyl group, a phenyl group optionally substituted by one or more substituents independently selected from halogen, C 1-4 alkyl and C14 alkoxy moieties, or a C110 alkyl group optionally substituted by one or more substituents independently selected from halogen, C14 alkoxy and phenyl moieties. Preferably R' is a phenyl group optionally substituted hy one or two substituents, preferably a single substituent in the 4-position, selected from fluorine, chlorine, bromine, C14 alkyl, and methoxy moieties. Advantageously R' is 4-fluorophenyl, 4-chlorophenyl, 4-t-butylphenyl or 4-methoxyphenyl.

If R2 represents an unsubstituted or substituted alkyl or alkenyl group, this group preferably has up to 6, more preferably 3 to 6, carbon atoms, and may be straight-chain or branched. It may for example be substituted by one or more fluorine, chlorine or bromine atoms, but is preferably unsubstituted. Thus R2 may for example represent a methyl, ethyl or, especially, isopropyl, group.

R2 conveniently represents a C36 branched alkyl group, or a C35 cycloalkyl group optionally substituted by one or more substituents selected from halogen, C16 alkyl, C26 alkenyl and C26 haloalkenyl. When R2 is C36 branched alkyl, it is preferably an isopropyl group.

The group R2 preferably represents a cyclopropyl group having the following general formula:

wherein Ra and Rb both represent hydrogen atoms, alkyl groups having from 1 to 6 carbon atoms, especially methyl groups, or halogen atoms, especially chlorine or bromine atoms; or Ra and R, together represent an alkylene group having from 2 to 6, especially 3, carbon atoms; or Ra represents a hydrogen atom and Rb represents an alkylene group having from 2 to 6 carbon atoms, especially an isobutenyl group, or a haloalkenyl group having from 2 to 6 carbon atoms and from 1 to 3 chlorine or bromine atoms, especially a mono- or dichloro-vinyl group;Rc and Rd both represent hydrogen atoms or alkyl groups having 1 to 6 carbon atoms, especially methyl groups, or Rc is hydrogen and Rd is an alkenyl group having from 2 to 6 carbon atoms, especially an isobutenyl group or a haloalkenyl group having from 2 to 6 carbon atoms and from 1 to 3 chlorine or bromine atoms, especially a mono- or dichlorovinyl group; or Rc and Rd together represent an alkylene group having from 2 to 6, especially 3, carbon atoms.

Most preferably, R2 represents an unsubstituted cyclopropyl group.

Especially preferred compounds of the general formula i are those in which R' represents a phenyl group, mono-substituted in the 4-position by a fluorine, chlorine or bromine atom or an alkyl or alkoxy group having up to 4 carbon atoms, and R2 represents an unsubstituted cyclopropyl group.

The compounds of the general formula I exhibit pesticidal, especially acaricidal, activity. As stated above a compound of the general formula I may exist in the form of the E- or the Z-isomer or a mixture thereof. The isomer in the form

may be referred to as the R2-cis isomer while the isomer in the form

may be referred to as the R'-cis isomer, In the preferred compounds of the general formula I wherein R2 is a cyclopropyl group and R1 is an aryl group, the R2-cis isomer is the E-isomer. Depending on the meanings of R' and R2, other possibilities for geometric and/or optical isomerism may exist, and the present invention should be understood to include all possible isomers of a compound of the general I and mixtures thereof.

The invention also provides a process for the preparation of a compound of the general formula I which comprises reacting an alkali metal salt of a compound of the general formula:

wherein R1 and R2 have the meanings given above, with a compound of the general formula

wherein X' and X2 have the meanings given above, and Hal represents a chlorine, bromine or iodine atom, especially a chlorine or bromine atom.

Preferably the reaction is carried out in a two-phase organic-inorganic system in the presence of a phase-transfer catalyst. The phase-transfer catalyst may be any compound which will accelerate interphase reactions in organic-inorganic two-phase systems. Tetrabutylammonium bromide is an example. Thus the compounds of the general formulae II and Ill may be mixed in the presence of aqueous potassium hydroxide, a suitable organic solvent for example methylene chloride, and a catalytic amount of a phase-transfer catalyst The reaction is suitably carried out under reflux.If the compound of the general formula II used as starting material is in substantially pure E-isomeric form, usually little or no isomerism takes place during the reaction and the resulting compound of the general formula I contains a high proportion of E-isomer.'Preferably a small excess of the compound of the general formula II is used, since some of this starting material may be hydrolysed under the reaction conditions.

The reaction may also be carried out by reacting the compound of the general formula II with sodium hydride in a suitable aprotic solvent, for example acetonitrile, tetrahydrofuran, or dimethylformamide in toluene, at a temperature in the range of from 60 to 1 000C. The compound of the general formula Ill, preferably in the form of a solution in the same solvent, may then be added to the resulting solution, and a reaction temperature of from 60 to 1 500 C, preferably from 100 to 1 1 OOC, is suitably maintained. The presence of the strong base sodium hydride in the resulting reaction mixture may cause some degree of isomerisation if substantially pure E-isomeric starting material is used, although the resulting compound of the general formula I usually contains a higher proportion of Eisomer than Z-isomer.

The invention also provides a pesticidal composition which comprises as active ingredient, a benzyloxime ether derivative of the general formula I, in association with an inert carrier. The invention also provides a method of combating pests at a locus, which comprises applying to that locus a benzyloxime ether derivative of the general formula I or a pesticidal composition according to the invention. The invention further provides the use of a benzyloxime ether derivative of the general formula I as a pesticide.

A carrier in a composition of the invention may be a solid or a liquid, including a material which is normally gaseous but which has been compressed to form a liquid, inorganic or organic, and of synthetic or natural origin. The active ingredient is suitably formulated with at least one carrier to facilitate its application to the locus, for example plants, seeds or soil, to be treated, or to facilitate storage, transport or handling.

Preferably a composition of the invention contains at least two carriers, at least one of which is a surface-active agent. The surface-active agent may be an emulsifier, a dispersing agent or a wetting agent; it may be non-ionic or ionic. Pesticidal compositions are generally formulated and transported in a concentrated form which is subsequently diluted by the farmer or other user before application. A surface-active agent facilitates this process of dilution.

Any of the carriers commonly used in the formulation of pesticides may be used in the compositions of the invention, and suitable examples of these are to be found, for example, in British Patent Specification No. 1,232,930.

The composition of the invention may for example be formulated as a wettable powder, microcapsules, a dust, granules, a solution, an emulsifiable concentrate, an emulsion, a suspension concentrate or an aerosol. The composition may have controlled release properties, or may be suitable for use as a bait.

Wettable powders usually contain 25, 50 or 75% w of active ingredient and may contain, in addition to inert solid material, 3-10% w of a dispersing agent and, where necessary, 0-10% w of a stabiliser, a penetrant and/or a sticker. A dust is usually formulated as a dust concentrate having a composition similar to that of a wettable powder but without a dispersant, and is diluted in the field with further solid carrier to give a composition usually containing ±1 0% w of active ingredient.

Granules usually have a size in the range of from 10 to 100 BS mesh (1.676-0.152 mm) and may be manufactured by agglomeration or impregnation techniques. Generally, granules will contain 2 25% w active ingredient and O10% w of additives, for example a stabiliser, slow release modifier and/or a binding agent.

Emulsifiable concentrates usually contain, in addition to a solvent, and, when necessary, co solvent, 10-50% w/v active ingredient, 2-20% w/v emulsifier and 0-20% w/v of other additives, for example a stabiliser, a penetrant and/or a corrosion inhibitor.A suspension concentrate is a stable nonsedimenting, flowable product and usually contains 1075% w active ingredient, 0.5-1 5% w of dispersing agent, 0.1-10% w of suspending agent, for example protective colloid and/or a thixotropic agent, and 0-10% w of other additives inciuding, for example, a defoamer, a corrosion inhibitor, a stabiliser, a penetrant and/or a sticker, and as dispersant, water or an organic liquid in which the active ingredient is substantially insoluble; certain organic additives and/or inorganic salts may be dissolved in the dispersant to assist in preventing sedimentation or as anti-freeze for water.

The aqueous dispersions and emulsions formed by diluting a wettable powder or an emulsifiable concentrate of the invention with water, also lie within the scope of the present invention. Such dispersions and emulsions may be of the water-in-oil or of the oil-in-water type, and may have a thick "mayonnaise"-like consistency.

A composition of the invention may also contain other ingredients, for example, one or more other compounds possessing pesticidal, herbicidal or fungicidal properties, or attractants, for example pheromones or food ingredients, for use in baits and trap formulations.

The following Examples illustrate the invention.

Example 1.

Preparation of cyclopropyl-4-fl uorophenyl ketoxime 2-chloro-6-fluorobenzyl ether (1) A reaction mixture consisting of 1.9 g (10.5 mmol) of the E-isomer of cyclopropyl-4-fluorophenyl ketoxime, 2.3 g (10 mmol) 2-chloro-6-fluorobenzyl bromide, 12 ml (12 mmol) aqueous potassium hydroxide (1 N), 0.05 g tetrabutylammonium bromide and 15 ml methylene chloride, was stirred under gentle reflux for five hours. The organic layer was separated, washed with 2N Na OH, dried over Mg SO4 and stripped of solvent to give 3.9 g of an orange oil. This oil was eluted from an SiO2 column with 1:1 toluene/hexane to give 2.3 g of 1, corresponding to a yield of 72%. This sample of 1 was substantially all E-isomer.

Refractive index n23 = 1.5657 Analysis: C H N Calculated for C17H14NCIF20 63.5 4.4 4.4 Found 63.9 4.4 4.3 Example 2.

Preparation of cyclopropyl-4-t-butylphenyl ketoxime 2 ,6-dichlorobenzyl ether (2) A solution of 2.17 g (10 mmol) of the E-isomerofcyclopropyl-4-t-butylphenyl ketoxime in 15 ml 20% dimethylformamide in toluene was added dropwise over 10 minutes to 1.0 g (40 mmol) of sod:um hydride in 20 ml of the same solvent. A solution of 2.1 5 g (11 mmol) of 2,6-dichlorobenzyl chloride in 1 5 ml of the same solvent was then added dropwise over 5 minutes, and the mixture was then stirred for 3 hours at 100 to 11 00C. After cooling the reaction mixture, 5 ml methanol were added thereto to inactivate untreated sodium hydride, and the mixture was poured onto a mixture of ice and 10 ml concentrated hydrochloric acid.The product was extracted with diethyl ether and washed first with saturated sodium carbonate solution and then with water until the washings were neutral. The solution was dried over magnesium sulphate and evaporated to give 2.7 g of a dark brown oil. This was eluted from an SiO2 column using toluene to give a solid product which after recrystallisation from hexane gave 1.2 g of 2, corresponding to a yield of 32%. This sample of 2 was substantially all E-isomer.

M.pt: 78-790C Analysis: C H N Calculated for C21H23NC120 67.0 6.2 3.7 Found 67.7 6.5 3.5 Example 3.

Preparation of cyclopropyl-4-fluorophenyl ketoxime 2,6-dichlorobenzyl ether (3) The procedure of Example 2 was followed using cyclopropyl-4-fluorophenyl ketoxime as starting material, with the exception that dry acetonitrile was used as solvent. 2.6 g of 3 as a white solid were obtained, corresponding to a yield of 58%. This sample of 3 contained 85% E-isomer.

M.pt:46-48 C Analysis: C H N CalculatedforC17H'4FCI2NO 60.3 4.1 4.1 Found 60.7 4.1 3.8 Examples 4-8.

The following compounds were prepared using the procedure of Example 2.

Cyclopropyl-4-methoxyphenyl ketoxime 2,6-dichlorobenzyl ether (50% E-isomer) (4).

Analysis: C H N Calculated for C18H'7NO2C12 61.7 4.9 4.0 Found 60.8 4.7 3.9 Cyclopropyl-4-chlorophenyl ketoxime 2,6-dichlorobenzyl ether (75% E-isomer) (5).

M.pt:80-81 C Analysis: C H N Calculated for C17H14NOCI3 57.6 4.0 4.0 Found 57.5 3.9 3.7 4-Fluorophenyl-isopropyl ketoxine 2-phloro-6-fluorobenzyl ether (E-isomer) (6).

n'8= 1.5473 Analysis: C H N Calculated for C17H18NOF2Cl 63.1 5.0 4.3 Found 63.6 5.3 4.3 4-Fluorobenzyl-isopropyl ketoxime 2-chloro-6-fluorobenzyl ether (50% E-isomer) (7).

n8 = 1.5442 Analysis: C H N Calculated for C17H16NOF2Ci 63.1 5.0 4.3 Found 63.5 5.3 4.5 4-Fluorobenzyl-isopropyl ketoxime 2-chloro-6-fluorobenzyl ether (Z-isomer) (8).

M.pt. 50-520C Analysis: C H N Calculated for C17H'6NOF2CI 63.1 5.0 4.3 Found 63.3 5.0 4.2 Example 9.

Pesticidal Activity of compounds of the invention.

The activities of the compounds prepared in Examples 1 to 8 were tested against the glasshouse red spider mite, tetranychus urticae, as follows: The compounds were formulated as solutions or suspensions in water containing 20% by weight of acetone and 0.05% by weight of Triton X-1 00 (Trade Mark) as wetting agent. The formulations contained 0.4% by weight of the compound to be tested. Leaf discs cut from French bean plants were held on moist filter paper placed on a lid inside a waxed carton. The discs were then sprayed using a logarithmic spraying machine, allowed to dry, and then infested with 10 adult mites. The discs were held under glasshouse conditions and, after 24 hours, the percentage of dead and moribund mites were assessed.

The concentration of material expected to kill 50% of the test species was calculated (LCso) and the toxicity of the compound was compared with that of the standard (parathion) and expressed as a Toxicity Index (T.l.).

LC50 of standard Toxicity Index = - x 100 LCso of test compound The LC50 used for the standard in this calculation was the mean value based on 20 determinations.

The results are given in the following Table.

TABLE

Structure of Compound with reference to Toxicity Index general formula I Percentage of against E-isomer in tetranychus Compound No. R R X X test compound urticae 1 4-fluorophenyl cyclopropyl F Cl > 95% 33 2 4-t-butylphenyl cyclopropyl Cl Cl > 95% 64 3 4-fluorophenyl cyclopropyl Cl Cl 85% 33 4 4-methoxyphenyl cyclopropyl Cl Cl 50% 12 5 4-chlorophenyl cyclopropyl Cl Cl 75% 12 6 4-fluorophenyl isopropyl F Cl > 95% 18 7 4-fluorophenyl isopropyl F Cl 50% 32 8 4-fluorophenyl isopropyl F Cl 5% 22

Claims (14)

1. A benzyloxime ether derivative of formula:

wherein R' is an optionally substituted aryl or alkyl group, R2 is an optionally substituted cycloalkyl, alkyl or alkenyl group, and X' and X2 are independently selected from fluorine, chlorine and bromine; in the form of its E isomer, its Z isomer or a mixture thereof.

2. A benzyloxime ether derivative according to Claim 1 wherein R1 is a naphthyl group, a phenyl group optionally substituited by one or more substituents independently selected from halogen, C1-8 alkyl and C1-4 alkoxy moieties, or a C1-10 alkyl group optionally substituited by one or more substituents independently selected from halogen, C1-4 alkoxy and phenyl moieties.

3. A benzyloxime ether derivative according to Claim 2 wherein R' is a phenyl group optionally substituted by one or two substituents selected from fluorine, chlorine, bromine, C 1-4 alkyl, and methoxy moieties.

4. A benzyloxime ether derivative according to Claim 3 wherein R1 is a phenyl group bearing a single substituent in the 4-position.

5. A benzyloxime ether derivative according to Claim 4 wherein R' is 4-fluorophenyl, 4 chlorophenyl, 44-butylphenyl or 4-methoxyphenyl.

6. A benzyloxime derivative according to any one of Claims 1 to 5 wherein R2 represents a C36 branched alkyl group, or a C6 cycloalkyl group optionally substituted by one or more substituents selected from halogen, C15 alkyl, C26 alkenyl and C26 haloalkenyl.

7. A benzyloxime ether derivative according to Claim 6 wherein R2 represents isopropyl.

8. A benzyloxime ether derivative according to Claim 6 wherein R2 represents a cyclopropyl group of formula

wherein Ra and Rb are both hydrogen atoms, C1-6 alkyl groups or halogen atoms, or Ra and Rb together represent a C2-6 alkylene group or Ra is hydrogen and Rb is C2-6 haloalkenyl having 1 to 3 chlorine or bromine atoms; Rc and Rd are both hydrogen atoms, C16 alkyl groups or halogen atoms, or Rc is hydrogen and Rd is C26 alkenyl or C26 haloalkenyl having 1 to 3 chlorine or bromine atoms, or Rc and Rd together represent a C26 alkenyl group.

9. A benzyloxime ether derivative according to Claim 8 wherein R2 is an unsubstituted cyclopropyl group.

10. A benzyloxime ether derivative according to Claim 1 as hereinbefore described in any one of Examples 1 to 8.

11. A process for preparing a benzyloxime ether derivative of formula I as defined in any one of Claims 1 to 10 which comprises reacting an alkali metal salt of a compound of formula

where R1 and R2 are as defined in Claim 1, with a compound of formula

where X' and X2 are as defined in Claim 1 and Hal represents a chlorine, bromine or iodine atom.

12. A process according to Claim 11 substantially as hereinbefore described in any one of Examples 1 to 8.

13. A benzyloxime ether prepared by a process according to Claim 11 or 12.

14. A pesticidal composition which comprises a benzyloxime ether derivative according to any one of Claims 1 to 10 and 13 in association with an inert carrier therefor.

1 5. A method of combating pests at a locus which comprises applying to the locus a benzyloxime ether derivative according to any one of Claims 1 to 10 and 13 or a composition according to Claim 14.