GB1600804A - Benzyloxime ethers having pesticidal properties their preparation their use as pesticides and pesticidal compositions containing them - Google Patents

Description

(54) BENZYLOXIME ETHERS HAVING PESTICIDAL PROPERTIES, THEIR PREPARATION, THEIR USE AS PESTICIDES AND PESTICIDAL COMPOSITIONS CONTAINING THEM (71) We, SHELL INTERNATIONALE RESEARCH MAATSCHAPPIJ B.V., a company organised under the laws of The Netherlands, of 30 Carel van Bylandtlaan, The Hague, The Netherlands do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The present invention relates to benzyloxime ethers having pesticidal properties, to their preparation, to their use as pesticides and to pesticidal compositions containing them.

The present invention is a modification of the invention claimed in our Application No. 7012/77, and provides a compound of the general formula

wherein R1 represents an unsubstituted or substituted aryl or alkyl group; R2 represents an unsubstituted or substituted cycloalkyl group; X represents an oxygen atom or a methylene group; and A represents a phenyl group which may be unsubstituted or substituted by one or more of the same or different substitutents selected from halogen atoms, alkyl groups and alkoxy groups. Those skilled in the art will appreciate that a compound of formula I may exist in the form of either its E-isomer or its Z-isomer or a mixture thereof.

An aryl group represented by R1 is preferably naphthyl 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 and 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. Preferably a phenyl group R' is mono- or dis-substituted, preferably having a substituent in the 4position.

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.

The group RZ preferably represents a substituted or unsubstituted cyclo-alkyl group of 3 to 6 ring carbon atoms, e.g. a cyclopropyl or cyclobutyl group, for example 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 R8 and Rb together represent an alkylene group having from 2 to 6, especially 3, carbon atoms; or Ra represents a hydrogen atom and Rb represents 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 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. Preferably R2 in the general formula I represents an unsubstituted cyclopropyl group.

Especially preferred compounds of the general formula I are those in which R1 represents a phenyl group, monosubstituted 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.

Preferably A represents an unsubstituted phenyl group. If the group A is substituted, it is preferably mono-substituted by a fluorine, chlorine or bromine atom or an alkyl or alkoxy group having from 1 to 4 carbon atoms; preferably the substituent is in the 4-position.

Preferably X is an oxygen atom.

Examples of specific compounds of the invention include those wherein, in general formula I, X represents oxygen, A represents unsubstituted phenyl, R2 represents unsubstituted cyclopropyl and R1 represents 4-methoxyphenyl 4chlorophenyl, 4-fluorophenyl and 4-t-butylphenyl.

The compounds according to the invention exhibit geometric isomerism about the oximic double bond, and the present invention extends to the individual E- and Z-isomers and to mixtures thereof. Substituents in R1 and R2 may lead to further isomerism, and in such a case the invention extends to all geometric and/or optical isomers and mixtures thereof.

The invention also provides a process for the preparation of a compound of the general formula I, which comprises dehydrating a compound of the general formula

wherein R1, R2, X and A have the meanings given above, using a suitable dehydrating agent. Any suitable mild dehydrating agent may be used, for example trifluoracetic anhydride.

The reaction is suitably carried out in an aprotic solvent, for example dioxan, at a temperature in the range 0 to 200 C.

The compound of the general formula II may be prepared by 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 Hal represents a chlorine, bromine or iodine atom, especially a chlorine or bromine atom, and X and A have the meanings given above. The reaction is suitably carried out in a two-phase organic/inorganic system in the presence of a phase transfer catalyst. The phase transfer catalyst may be any reagent which will accelerate interphase reactions in organic/inorganic two-phase systems.

Tetrabutylammonium chloride is an example. The organic phase is suitably methylene chloride, and the reaction is suitably carried out under reflux.

The alkali metal salt of the ketoxime of formula III may be prepared by the reaction of an alkali metal hydride, for example sodium hydride, with the ketoxime, or by reaction of aqueous potassium or sodium hydroxide with the ketoxime. The alkali metal salt of the ketoxime is preferably prepared in situ.

The compound of the general formula IV may be prepared by halogenation of a compound of the general formula

wherein X and A have the meanings given above, using a suitable halogenatingagent, for example N-bromosuccinimide, and subsequently reacting the resultant product with ammonia. The halogenation reaction is suitably performed in an inert solvent, for example carbon tetrachloride, under reflux. The amidation reaction is suitably performed in an inert solvent, for example toluene, at a temperature in the range -40 to OOC. The compound of the general formula V may be produced by reaction of the corresponding acid with a suitable chlorinating agent, for example, thionyl chloride, in an inert solvent, for example toluene.

The compounds of the invention have exhibited pesticidal, especially insecticidal, activity. The invention therefore provides a pesticidal composition which comprises as active ingredient a compound of the general formula I, together with a suitable carrier. The invention also provides a method of combating pests at a locus, which comprises applying to that locus a compound of the general formula I or a pesticidal composition according to the invention, the invention further provides the use of a compound 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, 010% w of a stabiliser, a penetrant and/or a sticker. A dust is usually formulated as a dust concentrate having an composition similar to that of a wettable powder but without a dispersant, and is diluted in the field with a further solid carrier to give a composition usually containing 2 10% 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 2125% w active ingredient and (#10% w of additives, for example a stabiliser, slow release modifier and/or binding agent.

Emulsifiable concentrates usually contain, in addition to a solvent, and, when necessary, co-solvent, 1050, w/v active ingredient, 2-20% w/v emulsifier and 020% w/v of other additives, for example a stabiliser, a penetrant and/or a corrosion inhibitor. A suspension cooncentrate is a stable, non-sedimenting, flowable product and usually contains 1075% w active ingredient, 0.515% w of dispersing agent, 0.110% w of suspending agent, for example protective colloid and for a thixotropic agent, and 010% w of other additives including, for example, a defoamer, a corrosion inhibitor, a stabiliser, a penetrant and/or a sticker, and as dispersent, 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-inoil 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 methoxyphenyl ketoxime a-cyano - 3 phenoxybenzyl ether 3-phenoxyphenylacetic acid (31.3 g, 137 mmol) was dissolved in toluene (150 ml) and thionychloride (18 g, 150 mmol) was added at room temperature. The reaction mixture was then warmed to gentle reflux over 1 hour, and then refluxed for 1 + hours. The solvent was then stripped from the solution in a rotary evaporator to give 3 - phenoxyphenylacetyl chloride as an orange oil.

The acid chloride was then dissolved in 100 ml anhydrous carbon tetrachloride.

N-bromosuccinimide (25.6 g, 144 mmol) and azo - bis - isobutyronitrile (approx.

0.1 g) were added, and the mixture was refluxed overnight. The mixture was then cooled in ice and filtered, and the solvent was stripped to give 47.3 g of an orange oil. .NMR analysis showed that the oil contained 80,' a - bromo - 3 phenoxyphenylacetyl chloride.

The crude product was dissolved in toluene, cooled in an ice/acetone bath, and excess ammonia gas (approx 10 g) was condensed into the mixture using a CO2/isopropyl alcohol condenser. The mixture was allowed to warm up to room temperature while stirring for 3 hours, and was then degassed using nitrogen. 100 ml water were added to dissolve ammonium chloride. The organic layer was separated, washed with sodium bicarbonate solution and dried over MgSO4. The solvent was stripped to give 42 g of an orange viscous oil which was chromatographed over silica gel using 3% acetone/toluene and recrystallised from cyclohexane to give a - bromo - 3 - phenoxyphenylacetamide.

The acetamide (3.3 g, 11 mmol) and cyclopropyl - 4 - methoxyphenyl ketoxime (1.9 g, 10 mmol) were mixed with 12 ml 1N KOH and 15 ml CH2Cl2. A few crystals of Bu4NCI were added and the mixture was stirred under gentle reflux for 6 hours, and then stirred at room temperature for 60 hours. The organic layer was separated, dried over MgSO4 and stripped of solvent to give 4.3 g of a yellow oil which partially solidified on standing. Toluene was added, and the remaining solid was filtered off and identified by NMR as cyclopropyl - 4 - methoxyphenyl ketoxime a - acetamido - 3 - phenoxybenzyl ether.

0.5 g (1.2 mmol) of this amide were dissolved in 10 ml dioxan and 0.2 ml (2.4 mmdl) of pyridine. The resulting suspension was cooled to 80C (it solidified if cooled further) and trifluoroacetic anhydride (0.3 g, 1.4 mmol) was added over 15 minutes. The reaction mixture was allowed to warm up to room temperature and was stirred for 3 hours. It was then difuted with CHCl3, washed with water and then saturated NaCI solution, and evaporated to yield 0.6 g of a yellowish oil. The oil was chromatographed over silica gel using CHCI3 as eluent to yield 0.2 g of the desired cyano compound as a white solid, m.pt. 83--84"C.

Analysis C H N Calculated for C25H22N2O3 75.4 5.6 7.0 Found 75.0 5.2 6.7 Example 2 Preparation of Cyclopropyl - 4 - chlorophenyl Ketoxime a - cyano - 3 phenoxybenzyl Ether This compound was prepared by the method described in Example 1. It had a m.pt. of 74--75"C and the following analysis.

C H N Calculated for C24H19N2O2C1 71.6 4.8 7.0 Found 72.5 4.5 6.7 Example 3 The insecticidal activity of the compounds according to the present invention was assessed employing the following pests: Musca domestica (M.d.) Spodoptera littoralis (S. 1.) The test methods employed for each species appear below: (i) Musca domestica (m.d.) A 0.4 / by weight solution in acetone of the compound to be tested was prepared and taken up in a micrometer syringe. Two to three day old adult female houseflies (Musca domestica) were anaesthetized with carbon dioxide, and 1 pl of the test solution was applied to the ventral side of the abdomen of each fly, 20 flies being tested. The treated flies were held in glass jars covered with paper tissue held by an elastic band. Cotton-wool pads soaked in dilute sugar solution were placed on top of the tissue as food. After 24 hours the percentage of dead and moribund flies was recorded.

(ii) Spodoptera littoralis (S. 1.) Pairs of leaves were removed from broad bean plants and placed on filter paper inside plastic petri dishes. The leaves were sprayed on the undersurface with a formulation containing 20% by weight of acetone, 0.05% by weight of Triton X-100 (Trade Mark) as wetting agent and 0.4% by weight of the compound to be tested. Varying concentrations were obtained by diluting the formulation. After spraying the leaves were left for oil hour drying period and then each leaf pair was infested with ten larvae of the Egyptian cotton leafworm (Spodoptera littoralis).

After 24 hours the percentage of dead and moribund larvae were recorded.

The results are shown in the following table in which the test species are identified by the initials noted above and the activity of each compound is expressed in the form of a Toxicity Index (T.I.) which is calculated from the following equation:- LC50 of ethyl parathion Toxicity Index (T.I.)= LC50 of test compound wherein LC50 is the lethal concentration required to kill 50% of the test species.

TABLE Compound prepared in Toxicity Index Example No. M.d. S.1.

1 36 6 2 64 70 WHAT WE CLAIM IS: 1. A compound of the general formula

wherein R' represents an unsubstituted or substituted aryl or alkyl group; R2 represents an unsubstituted or substituted cycloalkyl group; X - represents an oxygen atom or a methylene group; and A represents a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, alkyl groups and alkoxy groups.

2. A compound as claimed in claim 1, wherein R' represents a naphthyl 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 and alkoxy groups having from I to 4 carbon atoms.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (22)

**WARNING** start of CLMS field may overlap end of DESC **. C H N Calculated for C24H19N2O2C1 71.6 4.8 7.0 Found 72.5 4.5 6.7 Example 3 The insecticidal activity of the compounds according to the present invention was assessed employing the following pests: Musca domestica (M.d.) Spodoptera littoralis (S. 1.) The test methods employed for each species appear below: (i) Musca domestica (m.d.) A 0.4 /ó by weight solution in acetone of the compound to be tested was prepared and taken up in a micrometer syringe. Two to three day old adult female houseflies (Musca domestica) were anaesthetized with carbon dioxide, and 1 pl of the test solution was applied to the ventral side of the abdomen of each fly, 20 flies being tested. The treated flies were held in glass jars covered with paper tissue held by an elastic band. Cotton-wool pads soaked in dilute sugar solution were placed on top of the tissue as food. After 24 hours the percentage of dead and moribund flies was recorded. (ii) Spodoptera littoralis (S. 1.) Pairs of leaves were removed from broad bean plants and placed on filter paper inside plastic petri dishes. The leaves were sprayed on the undersurface with a formulation containing 20% by weight of acetone, 0.05% by weight of Triton X-100 (Trade Mark) as wetting agent and 0.4% by weight of the compound to be tested. Varying concentrations were obtained by diluting the formulation. After spraying the leaves were left for oil hour drying period and then each leaf pair was infested with ten larvae of the Egyptian cotton leafworm (Spodoptera littoralis). After 24 hours the percentage of dead and moribund larvae were recorded. The results are shown in the following table in which the test species are identified by the initials noted above and the activity of each compound is expressed in the form of a Toxicity Index (T.I.) which is calculated from the following equation:- LC50 of ethyl parathion Toxicity Index (T.I.)= LC50 of test compound wherein LC50 is the lethal concentration required to kill 50% of the test species. TABLE Compound prepared in Toxicity Index Example No. M.d. S.1.

1 36 6

2 64 70 WHAT WE CLAIM IS: 1. A compound of the general formula

wherein R' represents an unsubstituted or substituted aryl or alkyl group; R2 represents an unsubstituted or substituted cycloalkyl group; X - represents an oxygen atom or a methylene group; and A represents a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, alkyl groups and alkoxy groups.

2. A compound as claimed in claim 1, wherein R' represents a naphthyl 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 and alkoxy groups having from I to 4 carbon atoms.

3. A compound as claimed in either claim I or claim 2, wherein R' represents a

mono- or di-substituted phenyl group having a substituent in the 4-position.

4. A compound as claimed in claim 1, wherein R' represents an alkyl group having from I to 10 carbon atoms which may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, alkoxy groups and aryl groups.

5. A compound as claimed in claim 4, wherein R' represents an alkyl group having from I to 10 carbon atoms which may be unsubstituted or substituted by one or more of the same or different substituents selected from chlorine, fluorine and bromine atoms and methoxy and phenyl groups.

6. A compound as claimed in any one of claims 1 to 5, wherein R2 represents an unsubstituted or substituted cycloalkyl group having from 3 to 6 ring carbon atoms.

7. A compound as claimed in claim 6, wherein R2 represents a group of the general formula

wherein Ra and Rb both represent hydrogen atoms, alkyl groups having from 1 to 6 carbon atoms or halogen atoms, or Ra and Rb together represent an alkylene group having from 2 to 6 carbon atoms or Ra represents a hydrogen atom and Rb represents an alkenyl group having from 2 to 6 carbon atoms or a haloalkenyl group having from 2 to 6 carbon atoms and from 1 to 3 chlorine or bromine atoms; Rc and Rd both represent hydrogen atoms or alkyl groups having from 1 to 6 carbon atoms, or Rc represents a hydrogen atom and Rd represents an alkenyl group having from 2 to 6 carbon atoms or a haloalkenyl group having from 2 to 6 carbon atoms and from 1 to 3 chlorine or bromine atoms, or Rc and Rd together represent an alkylene group having from 2 to 6 carbon atoms.

8. A compound as claimed in claim 7, wherein R2 represents an unsubstituted cyclopropyl group.

9. A compound as claimed in claim 1, wherein R' represents a phenyl group which is 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.

10. A compound as claimed in any one of claims 1 to 9 wherein A represents a phenyl group which is mono-substituted by a fluorine, chlorine or bromine atom or an alkyl or alkoxy group having from 1 to 4 carbon atoms.

11. A compound as claimed in any one of claims 1 to 9, wherein A represents an unsubstituted phenyl group.

12. A compound as claimed in any one of claims 1 to Il, wherein X represents an oxygen atom.

13. A compound as claimed in claim 1, wherein X represents oxygen, A represents unsubstituted phenyl, R2 represents unsubstituted cyclopropyl and R' represents 4-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl or 4-t-butylphenyl.

14. A process for the preparation of a compound as claimed in claim I, which comprises dehydrating a compound of the general formula

wherein R1, R2, X and A have the meanings given in claim 1, using a suitable dehydrating agent.

15. A process as claimed in claim 14, wherein the compound of the general formula II is prepared by reacting an alkali metal salt of a compound of the general formula

wherein R' and R2 have the meanings given in claim 1, with a compound of the general formula

wherein Hal represents a chlorine, bromine or iodine atom, and X and A have the meanings given in claim 1.

16. A process as claimed in claim 15, wherein the compound of the general formula IV is prepared by halogenation of a compound of the general formula

wherein X and A have the meanings given in claim 1, using a suitable halogenating agent, and subsequently reacting the resultant product with ammonia.

17. A process as claimed in claim 14, carried out substantially as described in Example I herein.

18. A compound as claimed in claim 1, whenever perpared by a process as claimed in any one of claims 14 to 17.

19. The use of a compound as claimed in any one of claims 1 to 13 and 18, as a pesticide.

20. A pesticidal composition which comprises a compound as claimed in any one of claims 1 to 13 and 18, together with a suitable carrier.

21. A pesticidal composition as claimed in claim 20 which comprises at least two carriers, at least one of which is a surface-active agent.

22. A method of combating pests at a locus which comprises applying to that locus a compound as claimed in any one of claims 1 to 13 and 18 or a pesticidal composition as claimed in either claim 20 or claim 21.