GB2102418A - Improvements relating to pesticidal esters - Google Patents

Abstract

New pesticidal e.g. insecticidal compounds are of formula: <IMAGE> wherein Y represents -O-, -S-, -CO-, -CH2-, -CH=CH- or @C=CHX, X represents hydrogen, halogeno or an alkyl group, Z represents a -CH=C=CHY' group where Y' represents hydrogen or an alkyl group and R represents the residue of a carboxylic acid RCOOH which is an acid forming a pesticidal compound when esterified with alpha -cyano-3-phenoxybenzyl alcohol. The compounds can be prepared by conventional methods e,g. esterification.

Description

SPECIFICATION Improvements relating to pesticides This invention relates to pesticides and is particularly concerned with new pesticidal compounds, their preparation, pesticidal compositions containing them and their pesticidal use.

Since the discovery in the 1 940's of the structure of the naturally occurring pyrethrin insecticides, much research and development work has been directed to the production of synthetic analogues thereof. The naturally occurring insecticides are esters of certain cyclopropane carboxylic acids. Initially, investigations were directed to the production of new esters of the same cyclopropane-carboxylic acids from which the naturally occurring products are derived, but subsequently, investigations have been directed to esters in which the cyclopropane-carboxylic acid part of the molecule was modified and, more recently, it has been found that valuable insecticidal compounds can be prepared which are esters not of cyclopropane-carboxylic acids but which are esters of a-substituted phenyl acetic acids.

In developing new analogues of the naturally occurring insecticides, attention has been directed to the production of compounds having improved pesticidal properties while, at the same time, having an acceptably low level of toxicity to mammals, fish etc., and a sufficient level of physical stability so that the compounds can be used agriculturally, as well as for domestic and horticultural uses, without the need for repeated applications of the compound during a growing season.

We have now found that compounds of a new structural type have a particularly valuable combination of biological and physical 'prnperties rendering them useful as pesticidal compounds.

Accordingly, the present invention provides a compound of the general formula:

wherein Y represents

X represents hydrogen, halogeno or an alkyl group, Z represents a -CH=C=CHY' group where Y' represents hydrogen or an alkyl group and R represents the residue of a carboxylic acid RCOOH which is an acid forming a pesticidal compound when esterified with ar-cyano-3-phenoxybenzyl alcohol.

The compounds of the present invention may be regarded, structurally, as esters of the new alcohol of formula V

where Y and Z are as defined above and alcohols of formula V, together with their ester-forming derivatives, form a further aspect of this invention.

In the compounds of formula I and V, it is preferred that Y is -0- and Y' is hydrogen. When Y is the group CH=CHX, it is preferred that X is hydrogen. When Y' (or X) is alkyl, it is preferred that this is an alkyl group containing 1 to 4 carbon atoms and is particularly a methyl group. When Y' (or X) is halogen, it is preferred that the halogen is chlorine or bromine.

It is also preferred that, in the compounds of formula I and V, that the Ph-Y group be substituted at the 3-position on the benzyl ring.

In the compounds of formula I, R represents the residue of a carboxylic acid RCOOH which is an acid known to be capable of forming pesticidal compounds when esterified with -cyano-3- phenoxybenzyl alcohol. There are a large number of carboxylic acids that are known to form pesticidal compounds of this type and these carboxylic acids fall, for the most part, into two clearly defined groups. The first group are the cyclopropane carboxylic acids which are the compounds where R is a group of the formula:

In formula 11, R3 and R4 will normally be an alkyl group, usually the same alkyl group, containing 1 to 4 carbon atoms and, as is well-known in the art, dimethyl substitution normally gives high activity.

R2 in formula Il will normally be hydrogen or an alkyl group containing 1 to 4 carbon atoms and here, the experience of the art indicates that R2 will usually be hydrogen for maximum activity except in those compounds where R' is also an alkyl group in which case R2 preferably is an alkyl group, R', R2, R3 and R4 all conveniently being the same alkyl group, e.g. methyl.

In formula II, R1 can be hydrogen or a substituted or unsubstituted acyclic or carbocyclic group.

When R' is an unsubstituted hydrocarbyl group, it can be a straight chain or branched saturated or unsaturated acyclic or carbocyclic group such as an alkyl group, an alkenyl or alkadienyl group or a cycloalkyl, cycloalkylalkyl or cycloalkylalkenyl group. These hydrocarbyl groups preferably contain up to 10, particularly up to 6 carbon atoms.

When group R1 is substituted, it is preferably one of the hydrocarbyl groups mentioned above which is substituted by one or more halogeno groups which may be fluorine, chlorine or bromine or by an alkoxy or oximino group. When the substituents are two or more halogeno substituents, the halogeno substituents need not necessarily be the same halogen while when alkoxy groups are present, these preferably contain up to 4 carbon atoms and will normally be methoxy groups.

One particularly valuable structure for the group R' is of formula IV

where R7 and Ra, which may be the same or different, are each alkyl group containing 1 to 4 carbon atoms, a trifluoromethyl group or a halogeno group, which may be the same or different and are preferably fluorine, chlorine or bromine. One of R7 and Ra may also represent hydrogen or a phenyl or substituted phenyl group. Alternatively, R7 and Ra may together form a straight or branched substituted or unsubstituted saturated or unsaturated divalent hydrocarbon chain which may be substituted by one or more hetero atoms e.g.O, N or S, so that R7 and R8 together with the carbon atom to which they are attached forms a carbocyclic or heterocyclic ring which will preferably contain 5 to 7 ring atoms, optionally 1 or 2 carbon-to-carbon double bonds and optionally one or more alkyl (C1-C4) or halogeno substituents on the cycloaliphatic ring. Other compounds of interest are those in which R is a group of the structure

where the dotted line represents an optical double bond and X represents H or halogen such as chlorine.

Specific cyclopropane carboxylic acids from which the compounds I of the present invention may be structurally derived include the following: Chrysanthemic acid including particularly (1 R)-trans chrysanthemic acid; Pyrethric acid; Dimethylcyclopropane carboxylic acid; Trimethylcyclopropane carboxylic acid; Tetramethylcyclopropane carboxylic acid; 2,2-Dirnethyl-3-(cyclopentylidenemethyl)cycloprnpane carboxylic acid; 2,2-Dimethyl-3-(dibromovinyl)cyclopropane carboxylic acid; particularly the (1 R)-cis isomer thereof; 2.2-Dimethyl-3-(dichlorovinyllcyclopropane carboxylic acid; particularly the (1R)-cis isomer thereof; 2,2-Dimethyl-3-(1 ,2,2,2-tetrabromoethyl)cyclopropane carboxylic acid; 2,2-Di methyl-3-( 1 ,2-dibromo-2 ,2-dich loroethyl)cyclopropane carboxylic acid; 2,2-Dimethyl-3-(2-ch loro-3,3,3-trifluoropropenyl)cyclopropane carboxylic acid; 2,2-Dimethyl-3-(tetrahydro-2-oxo-thien-3-ylidenemethyl)cyclopropane carboxylic acid.

The second major class of carboxylic acids from which the esters of formula I may be structurally derived are the n-substituted aryl acetic acid esters. In these compounds R in formula I will normally be of the structure Ill

wherein Ar represents an aryl residue, R5 represents a saturated or unsaturated straight chain or branched acyclic or cyclic hydrocarbon residue and R6 represents hydrogen or one or more alkyl, alkoxy (including substituted alkoxy such as OCF3 and 0CHEF2) or halogeno substituents.

Ar will normally be an aryl residue based on a benzene ring although other aryl residues, e.g.

polynuclear residues are also of interest. R5 will normally be a saturated straight or branched chain hydrocarbon group, particularly an alkyl group containing up to 8 carbon atoms and it is often desirable that this alkyl group should contain at least one secondary carbon atom particularly when that secondary carbon atom is directly bonded to the carbon atom directly bonded to the R5 substituted aryl group. Thus R5 is preferably an isopropyl group or a secondary butyl group. R5 can also be a cycloaliphatic residue, again preferably containing a secondary carbon atom located immediately adjacent to the carbon atom carrying the R6 substituted phenyl group, e.g. R5 may be a cyclopropyl group or an alkyl substituted cyclopropyl group. R5 can also be a cycloalkylalkyl group.

R6 is preferably one or more halogeno or halogeno-containing substituents, e.g. F, Cl, Br or OCHF2 or OCF3 and, when more than one halogeno or halogen-containing substituent is present, they will normally be but are not necessarily the same halogen. When R6 is an alkyl or alkoxy group, these preferably contain up to 4 carbon atoms and again, when more than one such group is present, they need not necessarily be the same groups. When only one substituent R6 is present, it is preferably present in the para-position. When more than one R6 substituent is present, the para-position is preferably substituted together with one or more of the ortho and meta positions.

Another class of carboxylic acids from which the esters of the present invention may be structurally derived are -substituted arylamino acetic acids of the type

where R5, R6 and aryl are as defined above.

Specific a-substituted phenyl acetic acids from which esters of the formula I may be structurally derived include: a-lsopropyl-p-ch lorophenyl acetic acid; (x-Cyclopropyl-p-chlorophenyl acetic acid; (x-Cyclopropyl-p-methylphenyl acetic acid; a-lsopropyl-p-(difluoromethoxy)-phenyl acetic acid; -lsopropyl-(2-chloro-4-trifluoromethyl anilino) acetic acid.

The compounds of the invention may exhibit geometrical and/or optical isomerism.

The compounds of the invention exhibit optical isomerism in that the carbon atom bearing the substituent Z can exist in the R or S configuration and the present invention includes compounds in which the configuration is substantially completely R or in which the configuration is substantially completely S or mixtures thereof.

Compounds of the invention in which R represents a substituted cyclopropane residue of formula II can exist in the form of both geometrical and optical isomers. This is because of the unsymrnetrical substitution at C, and C3 of the cyclopropane ring. Compounds of the present inventor I include those isomers in which the hydrogen atoms at C1 and C3 of the cyclopropane ring are substantially completely in the cis configuration or substantially completely in the trans configuration or mixtures thereof. The present invention also includes compounds in which the configuration at C1 is substantially completely R or substantially completely S and mixtures thereof.In the compounds of the invention in which R represents a group of formula II, the optical configuration at C1 and C3 cannot vary independently of the geometrical configuration of the hydrogen atoms at C1 and C3 of the cyclopropane ring. The effect of this is that the configuration of the cyclopropane ring can be defined uniquely by specifying the optical configuration at C1 and the geometrical configuration of the hydrogen atoms at C1 and C3 and, for definition purposes, we have adopted nomenclature of the form (1 R)-cis, (1 R)-trans etc. it being unnecessary to specify the optical configuration at C3 which is fixed once the other two variables are defined.Adopting this nomenclature avoids the confusion which can arise by having to designate either R or S to the same optical configuration at C3 depending upon the nature of the substituents on the cyclopropane ring and even those on the side chain.

When R is a group of formula II in which R' is a group of formula IV in which the substitution about the ethylenic bond is asymmetrical, that is to say R7 + R8 then the configuration of this part of the molecule can be substantially completely in the E form or substantially completely in the Z form or a mixture thereof.

When R is a group of formula Ill, the carbon atom to which R5 is bonded can exist substantially completely in the S configuration or substantially completely in the R configuration or can be a mixture of the two forms.

Compounds of the invention in which Y' represents alkyl or halogen can exist in the form of E or Z isomers in view of the asymmetric substitution on the carbon atoms linked by the olefinic bond and the present invention includes both the substantially pure E and substantially pure Z isomers as well as mixtures thereof.

The compounds of the present invention can be in the form of single isomers but, having regard to the fact that the compounds have at least one and frequently more than one centre of asymmetry, the compounds of the invention will normally be in the form of isomer mixtures although these isomer mixtures can be optically active and/or substantially completely in one geometric form.

The compounds of the present invention can be prepared by reaction of alcohol IV or an esterifiable derivative thereof of formula

with a carboxylic acid or esterifiable derivative thereof of formula RCOQ where R, Y and Z are as defined above and Q and Q1 are reactive groups that react together to form an ester linkage. It is usually convenient in practice either to react a salt of the carboxylic acid, e.g. a silver or triethylammonium salt with a benzylhalide derivative, that is to say a 1 -(3-phenoxyphenyl)buta-2,3-dienyl halide, but one can also react the acid or acid halide for example with the alcohol in the presence of suitable catalysts etc.

Alternatively, the esters of the invention can be prepared by transesterification by reacting a C1C6 alkyl ester of the carboxylic acid with the benzyl alcohol of formula V in the presence of a basic transesterification catalyst. This method is not usually satisfactory where the molecule contains another base-sensitive residue, e.g. where the carboxylic acid is pyrethric acid.

The esters of the present invention may also be prepared by converting the c-ethynyl group in the corresponding cr-ethynyl benzyl carboxylate of the formula

into an alkadienyl group by the synthesis described below.

The key to the synthesis of the pesticidal esters of the present invention are the new alcohols of formula V

The synthesis of the new alcohols can be achieved by reacting a 1 -(substituted phenyl)propargyl alcohol with an aldehyde in the presence of cuprous bromide and diisopropylamine in a modification of the procedure described in Tetrahedron Letters 1980, 929.

One or more of the pesticidal esters of formula I can be formulated with an inert carrier or diluent to give pesticidal compositions and such compositions form a further aspect of the present invention.

These compositions can be in the form of dusts and granular solids, wettable powders, mosquito coils and other solid preparations, or as emulsions, emulsifiable concentrates, sprays and aerosols and other liquid preparations after the addition of the appropriate solvents, diluents and surface-active agents.

The pesticidal compositions of the invention will normally contain from 0.001 to 25% by weight of the compound of formula I but the compositions can contain higher concentrations of active ingredient of formula I e.g. up to 95% for compositions to be sold as concentrates for dilution before use by the ultimate user.

The compositions of the invention can include diluents such as hydrocarbon oils, e.g. xylene or other petroleum fractions, water, anionic, cationic or nonionic surface-active agents, anti-oxidants and other stabilisers as well as perfumes and colouring matters. These inert ingredients may be of the type and in proportions such as are conventionally used in pesticidal compositions containing pyrethroid-like compounds.

In addition to these inactive ingredients, the compositions of the present invention may contain one or more further active ingredients which may be other pesticidal compounds of the pyrethroid type or of other types and the composition may also include synergists of the type known to be capable of synergising the activity of natural pyrethrin and pyrethroid-like insecticides, synergists of this type include piperonyl butoxide, tropital and sesamex.

The compounds of formula I can be used to control pest infestation in the domestic, horticultural or agricultural or medical including veterinary areas. The compounds or compositions of the invention can be used to combat pest infestation by treating pests or surfaces or environments susceptible to pest infestation with effective amounts of the active compounds of formula I or of compositions containing them.For example, they may be used in a domestic environment for spraying rooms to combat infestation with houseflies or other insects, they can be used for treatment of stored dry crops or cereals to combat infestation by insects or other pests, they can be used to spray growing crops, e.g. cotton or rice to combat infestation by common pests and finally, they can be used in a medical or veterinary field, e.g. as a cattle spray to prevent or treat infestation by insects or other pests.

The following Examples are given to illustrate the invention. Temperatures are in OC.

EXAMPLE 1 1 -(3-phenoxyphenyl)buta-2,3-dienyl (1 R,trans) ch rysanthemate (a) A mixture of 1 -(3-phenoxyphenyl)propargyl alcohol (2.24 g, 10 mmol), cuprous bromide (0.48 g), paraformaldehyde (0.3 g), di-isopropylamine (1.1 g) and dioxane (10 cm3) was refluxed for 30 minutes, cooled, poured onto 2M HCI (150 cm3) and extracted with dichloromethane (150 cm3 x 3).

The combined extracts were washed thoroughly with 2M HCI, water, saturated sodium chloride, dried and the solvent evaporated off. The residue was chromatographed on silica gel t.l.c. plates eluted with 40% diethyl ether/hexane. Yield of 1 -(3-phenoxyphenyl)buta-2,3-dienol 1 g (42.7%) n020 1.6008.

(b) To a stirred solution of the alcohol from (a) above (0.2 g, 0.84 mmol) and pyridine (0.07, 0.89 mmol) in dry benzene (5 cm3) was added 1 R, trans chrysanthemic acid chloride (0.1 5 g, 0.79 mmol).

After 4 hours, the mixture was passed through an alumina column (5 g) and eluted with benzene. The eluate was evaporated to give the title product (Compound 1). Yield 0.25 g (76%) n201.5568.

EXAMPLE 2 The procedure described in Example 1 was repeated but replacing the chrysanthemic acid chloride by (1 R,cis)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid chloride to give 1-(3 phenoxyphenyl)-buta-2,3-dienyl (1 R,cis)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylate, 20 n0 1.5912 (Compound 2).

The pesticidal activity of esters of formula I of the invention was assessed against houseflies and mustard beetles using the following techniques: Houseflies (Musca domestica) Female flies were treated on the thorax with a one microlitre drop of-insecticide dissolved in acetone. Two replicates of 1 5 flies were used at each dose rate and 6 dose rates were used per compound under test.After treatment, the flies were maintained at a temperature of 200C + 1 and kill was assessed 24 and 48 hours after treatment. LD50 values were calculated in micrograms of insecticide per fly and relative toxicities were calculated from the inverse ratios of the LD50 values (see Sawicki et al, Bulletin of the World Health Organisation, 35, 893, (1966) and Sawicki et al, Entomologia and Exp.Appl. 10, 253, (1967)).

Mustard Beetles (Phaedon cochleariae Fab) Acetone solutions of the test compound were applied ventrally to adult mustard beetles, using a microl drop applicator. The treated insects were maintained for 48 hours after which time kill is assessed. Two replicates of 40 to 50 mustard beetles were used at each dose level and 5 dose levels were used for each compound. Again, LD50values were calculated and relative toxicities were calculated for the inverse ratios of LD50 (see Elliott et al, J. Sci. Food Agric. 20, 561, (1969)).

Relative toxicities were calculated by comparison with 5-benzyl-3-furylmethyl (1 R-trans chrysanthemate (Bioresmethrin) which is one of the more toxic chrysanthemate esters known to houseflies and mustard beetles, its toxicity being about 24 times that of allethrin to houseflies and 65 times that of allethrin to mustard beetles.

The following relative toxicities were recorded.

RELATIVE TOXICITY

Compound Houseflies Mustard Beetles Bioresmethrin 100 100 1 3.8 1.2 2 43 3.6 Compounds of formula I may be formulated as the active compound or as one of the active compounds in pesticidal compositions as described in the Formulation Examples below.

Formulation 1 Oil-based liquid spray for household insects active compound 0.015% w/v 25% Pyrethrum Extract 0.25% Piperonyl butoxide 0.5% Antioxidant 0.1% Odourless light oil solvent e.g. xylene to make 100 vols.

Formulation 2 Water-based liquid spray concentrate for mosquito control active compound 0.25% w/v Piperonyl butoxide 1.0% Non-ionic emulsifier 0.25% Antioxidant 0.1% Water to make 100 vols.

This concentrate should be diluted e.g. 1:80 v/v with water, before spraying.

Formulation 3 Aerosol active compound 0.05% 25% Pyrethrum Extract 0.8% Piperonyl butoxide 1.5% Odourless petroleum distillate (b.p. 200--2650) 17.338% Propellant, e.g. a mixture of equal quantities of trichloromonofluoromethane and dichlorodifluoromethane 80.0% Perfume 0.2% Antioxidant O. 1 O/o Formulation 4 Mosquito coil active compound 0.25% Tabu powder (also known as pyrethrum marc) 30.0% Filler(s), e.g. wood flour, powdered leaves or nut shells 68.75% Brilliant Green (dyestuff) 0.5% p-Nitrophenol 0.5% Formulation 5 Emulsifiable concentrate active compound 1.5% w/w Non-ionic emulsifier 25.0% Xylene 73.4% Antioxidant 0.1% This concentrate may then be diluted at the rate of 30 mls. to 42 litres of water prior to use.

Formulation 6 General purpose powder for household, garden, livestock or grain storage use active compound 0.05% w/w Tropital (the synergist piperonyl-bis 2-[2'-n-butoxyethoxy)ethyl acetal 0.25% Antioxidant, e.g. butyl hydroxy toluene or butyl hydroxy anisole 0.03% Filler 99.67%

Claims (1)

1. A compound of formula:

wherein Y represents

X represents hydrogen, halogeno or an alkyl group, Z represents a -CH=C=CHY' group where Y' represents hydrogen or an alkyl group and R represents the residue or a carboxylic acid RCOOH which is an acid forming a pesticidal compound when esterified with sw-cyano-3-phenoxybenzyl alcohol.

2. A compound according to claim 1 wherein R is a group of the formula:

wherein R1 represents hydrogen or a substituted or unsubstituted acyclic or carbocyclic group, R2 represents hydrogen or an alkyl group and R3 and R4 each represent an alkyl group.

3. A compound according to claim 2 wherein R is the residue from chrysamthemic acid or 3-(2,2 dibromovinyll-2,2-dimethyl-cyclopropane carboxylic acid.

4. A compound according to claim 3 wherein the acid has 1 R cis configuration.

5. A compound according to claim 1 wherein R represents a group of formula:

wherein Ar represents an aryl residue, R5 represents a saturated or unsaturated straight chain or branched acyclic or cyclic hydrocarbon residue and R6 represents. hydrogen or one or more alkyl, alkoxy (including substituted alkoxy such as OCF3 and OCHF2) or halogeno substituents.

6. A compound according to claim 1 wherein R represents a group of formula:

wherein R5, R6 and Ar are as defined in claim 5.

8. A compound according to claim 1 hereinbefore specifically mentioned.

9. A process for the production of a compound of formula I as defined in claim 1 which comprises reacting a carboxylic acid or esterifiable derivative thereof of formula RCOQ with an alcohol or esterifiable derivative thereof of formula

wherein R, Y and Z are as defined in claim 1 and 0 and Q1 are reactive groups which react together to form an ester linkage.

10. A process according to claim 9 substantially as hereinbefore described with reference to any one of the Examples.

11. A pesticidal composition comprising a compound according to any one of claims 1-8 together with an inert diluent or carrier.

12. A pesticidal composition according to claim 11 substantially as hereinbefore described with reference to any one of the Examples.

1 3. A method of pest control which comprises applying to a pest or to a surface or environment susceptible to pest attack a compound according to any one of claims 1-8 or a composition according to claim 11 or 12.

14. A compound of the formula:

wherein Y and Z are as defined in claim 1.

1 5. A compound according to claim 14 wherein Y represents 0 and Y' represents H.