GB2100263A - Cyclopropane carboxylate esters and their use as pesticides - Google Patents

Abstract

There are provided cyclopropanecarboxylate esters of formula <IMAGE> wherein R<1> and R<2> are independently selected from hydrogen, fluorine, chlorine and bromine atoms, Y is hydrogen, cyano or ethynyl, and Z<1> and Z<2> are independently selected from hydrogen, fluorine, chlorine and bromine atoms; methods for their manufacture; pesticidal compositions containing them and their use as pesticides.

Description

SPECIFICATION Cyclopropanecarboxylate esters and their use as pesticides This invention relates to cyclopropanecarboxylate esters, to their preparation and to compositions containing them for use as pesticides, especially as insecticides.

According to the present invention there are provided cyclopropanecarboxylate esters of formula

wherein R' and R2 are independently selected from hydrogen, fluorine, chlorine and bromine atoms, Y is hydrogen, cyano or ethynyl, and Z1 and Z2 are independently selected from hydrogen, fluorine, chlorine and bromine atoms.

It should be noted that the compounds of formula I possess three, four or five centres of asymmetry, depending on the nature of the substituent Y, and on whether R1 and R2 represent the same or different moieties. Accordingly, as will be appreciated by those skilled in the art, the compounds of formula I may exist as individual geometrical and optical isomers, mixtures of isomers and racemates. In general mixtures of isomers wherein the 2-R1-2-R2-cyclopropyl group and the carboxylate group are in cis-configuration relative to one another ("cis isomers") are preferred over mixtures of isomers wherein those groups are in trans-configuration relative to one another ("trans-isomers").

Preferred esters of formula I have one or more of the following features:- (i) Y is hydrogen or cyano, (ii) Y is cyano, (iii) Z1 is a hydrogen or bromine atom and Z2 iS a hydrogen or fluorine atom, provided that at least one of Z1 and Z2 is a hydrogen atom, (iv) R1 is the same as R2, (v) Z1 and Z2 are both hydrogen atoms, and (vi) R1 and R2 are both hydrogen, fluorine or chlorine atoms.

The cyclopropanecarboxylate esters may be prepared by methods analogous to those use for known compounds. A convenient process comprises reacting a compound of formula

with a compound of formula

wherein R1, R2, Y, Z1 and Z2 are as defined above, one of P and W represents a halogen atom, preferably a chlorine or bromine atom, and the other represents a hydroxy group. Conveniently P is a hydroxy group and W is a halogen atom. The reaction is preferably carried out in the presence of a suitable base, for example a tertiary amine such as triethylamine or an alkali metal carbonate such as sodium or potassium carbonate.

Compounds of formula III are either known compounds or may be prepared from known materials in known manner. (See e.g. UK Patent Specification No. 1,413,491).

Compounds of formula II may be prepared from the appropriate isomer or isomers of an alkyl 2,2- dimethyl-3-vinylcyclopropane carboxylate of formula

wherein R is an alcohol residue, e.g. an alkyl group of 1 to 6 carbon atoms, preferably an alkyl group of 1 to 4 carbon atoms such as methyl or tertiary butyl, by reaction with a carbene of formula CR1R2 to produce a compound of formula

The carbene of formula CR1R2 may be generated in known manner.

The compound of formula V may be hydrolysed under acid or alkaline conditions, conveniently using hydrobromic acid and acetic acid, or aqueous alcoholic sodium or potassium hydroxide, to give a compound of formula II wherein P represents a hydroxy group, which may if desired be converted to a compound of formula Il wherein P represents a halogen atom in known manner, e.g. by reaction with thionyl chloride, conveniently in an inert solvent such as benzene, to give the acid chloride of formula II.

The cyclopropanecarboxylate esters according to the invention are of interest as pesticides, especially as insecticides for domestic and agricultural outlets. The invention therefore also provides a pesticidal composition which comprises an ester of formula I as defined above in association with an inert carrier. The invention further provides a method of combating pests, e.g. insect pests, at a locus which comprises applying to the locus an ester of formula I or a composition in accordance with the invention.

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, 310% w of a dispersing agent and, where necessary, 0-10% w of a stabiliser, a pentrant 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% 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 cqntain 225% w active ingredient and 0-10% 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, cosolvent, 1050% w/v active ingredient, 220% w/v emulsifier and 020% 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 0.515% w of dispersing agent, 0.110% of suspending agent, for example protective colloid and/or 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 a 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 invention will be further understood from the following Examples.

EXAMPLE 1 Preparation of trans-3-phenoxybenzyl 3-cyclopropyl-2,2-dimethylcyclopropanecarboxylate (1) Copper powder (5.08 g, 80 mM), iodine (0.11 g, 0.9 mM) and benzene (20 ml) were stirred together at ambient temperature until the iodine colour disappeared (15 minutes). Trans-methyl 2,2 dimethyl-3-vinylcyclopropanecarboxylate (3.0 g, 19.5 mM) (prepared by the method described in Ag.Biol.Chem., 38, pages 827 to 830) and diiodomethane (10.2 g, 38 mM) were added and resulting reaction mixture was refluxed for 1 84 hours, when analysis of a small sample indicated 65% conversion of the methyl trans-2,2-dimethyl-3-vinylcyclopropanecarboxylate. The reaction mixture was diluted with diethyl ether (50 ml) and filtered.The filtrate was evaporated and the resulting trans-methyl 3cyclopropyl-2,2-dimethylcyclopropanecarboxylate was hydrolysed without further purification by adding ethanol (25 ml) and 2N aqueous sodium hydroxide solution (25 ml) and allowing to stand overnight at ambient temperature. The reaction mixture was diluted with water and extracted with diethyl ether. The aqueous phase was separated off, acidified with dilute hydrochloric acid and extracted twice with 20 mi portions of diethyl ether. The combined ether extracts were washed with water, dried over magnesium suphate and evaporated to give trans-3-cyclopropyl-2,2-dimethylcyclopropanecarboxylic acid as a yellow oil (1.4 g, 42%).

Trans-3-cyclopropyl-2,2-dimethylcyclopropanecarboxylic acid (0.7 g, 4.55 mM), 3- phenoxybenzylbromide (1.1 g, 4.2 mM) and potassium carbonate (0.6 g, 4.6 mM) in acetone (25 ml) were stirred together for 1 6 hours at ambient temperature and the reaction mixture was then refluxed for 1 hour, diluted with water and extracted twice with 20 ml portions of diethyl ether. The combined ether extracts were washed with saturated aqueous solutions of sodium bicarbonate and of sodium chloride, dried over magnesium sulphate and evaporated to yield a yellowish oil (1.3 g), which was purified on a silica column using toluene as eluant to give trans-3-phenoxybenzyl 3-cyclopropyl-2,2dimethylcyclopropanecarboxylate (1) (0.8 g, 57%) as an oil, 22 1.551.

Analysis: C22H24O3: C H Calculated: 78.5 7.2 Found: 78.3 7.2 EXAMPLE 2 Preparation of trans-a-cyano-3-phenoxybenzyl 3-cyclopropyl-2,2-dimethylcyclopropanecarboxylate (2) Trans-3-cyclopropyl-2,2-dimethylcyclopropanecarboxylic acid (0.7 g, 4.55 mM), a-cyano-3phenoxybenzyl bromide (1.15 g, 4.0 mM) and potassium carbonate (0.6 g, 4.6 mM) in acetone (25 ml) were stirred together for 4 hours at ambient temperature. The reaction mixture was then diluted with water and extracted twice with 20 ml portions of diethyl ether.The combined ether extracts were washed with saturated aqueous solutions of sodium bicarbonate and of sodium chloride, dried over magnesium sulphate and evaporated to yield a yellow oil (1.4 g), which was purified on a silica column using toluene as eluant to give trans-a-cyano-3-phenoxybenzyl 3-cyclopropyl-2,2dimethylcyclopropane carboxylate (2) (0.8 g, 56%) as an oil nod21.551.

Analysis: C23H23NO3: C H N Calculated: 76.4 6.4 3.9 Found: 76.6 6.5 5.0 EXAMPLE 3 By a method similar to that of Example 2 there was prepared: 3 cis-a-cyano-3-phenoxybenzyl 3-cyclopropyl-2,2-dimethylcyclopropanecarboxylate (yield 47%) oil nD2 1.552.

Analysis: C23H23NO3: C H N Calculated: 76.4 6.4 3.9 Found: 76.1 6.4 3.8 EXAMPLE 4 Preparation of trans-3-phenoxybenzyl 3-(2,2-difluorocyclopropyl)-2,2-dimethylcyclopropa ne carboxylate (4) Trans-methyl 2,2-dimethyl-3-vinylcyclopropanecarboxylate (3.0 g, 19.5 mM) and dry sulpholane (15 ml) were heated together at about 1 600C. Sodium difluorochloroacetate (9 g) was added portionwise (effervescence occurred) and the temperature of the reaction mixture was maintained at about 1 6O0C for 1 6 hours. The reaction mixture was allowed to cool, was diluted with water and was extracted twice with 20 ml portions of diethyl ether.The combined ether extracts were washed with water, dried over magnesium sulphate and evaporated to yield trans-methyl 3-(2,2 difluorocyclopropyl)-2,2-dimethylcyclopropanecarboxylate as a dark oil (1.6 g, 40%), which was hydrolysed without further purification to give trans-3-(2,2-difluorocyclopropyl)-2,2- dimethylcyclopropanecarboxylic acid which was in turn esterified to give trans-3-phenoxybenzyl 3-(2,2 difluorocyclopropyl)-2,2-dimethylcyclopropanecarboxylate (4), by methods similar to those of Example 1 ,as an oil (yield 34%) nDl 1.533.

Analysis: C22H22O3F2: C H Calculated: 71.0 6.0 Found: 72.4 6.3 EXAMPLES 5 AND 6 By methods similar to that of Example 2 there were prepared: 5 trans--cyano-3-phenoxybenzyl 3-(2,2-difl uorocyclopropyl)-2,2-dimethylcyclopropanecarboxylate (yield 37%) oil nD' 1.533.

Analysis: C23H2rNO3F2: C H N Calculated: 69.6 5.3 3.6 Found: 69.9 5.6 3.6 6 cis-a:-cyano-3-phenoxybenzyl 3-(2,2-difluorocyclopropyl)-2,2-dimethylcyclopropanecarboxylate (yield 18%) oil no31.534.

Analysis: C23Hz1NO3F2: C H N Calculated: 69.6 5.3 3.6 Found: 69.6 5.5 3.6 EXAMPLE 7 Preparation of trans-3-phenoxybenzyl 3-(2 ,2-dichlorocyclopropyl)-2 ,2-di methylcyclop ropaneca r- boxylate (7) Trans-methyl 2 .2-dimethyl-3-vinylcyclopropanecarboxylate (3.0 g, 19.5 mM), dimethyldigol (5 ml) and tetrachloroethylene (20 ml) were heated together under reflux. Seven portions of sodium trichloracetate (each of 3.7 g, 20 mM) were added over 11 days. The reaction mixture was then allowed to cool, was diluted with water and extracted twice with 20 ml portions of dichloromethane.The combined dichloromethane extracts were washed with water, dried over magnesium sulphate and evaporated to yield a dark-brown residue (4.6 g) which was purified on a silica column, using toluene as eluant, to yield trans-methyl 3-(2,2-dichlorocyclopropyl)-2,2-dimethylcyclopropane carboxylate as a white oil (f 36-60) (2.8 g, 61%). This white oil (2.8 g, 11.8 mM), 2N aqueous sodium hydroxide solution (30 ml) and ethanol (30 ml) were stirred together at ambient temperature for 1 hour. The reaction mixture was then diluted with water and extracted with diethyl ether. The aqueous phase was separated off, acidified with dilute hydrochloric acid and extracted twice with 20 ml portions of diethyl ether. The combined ether extracts were washed with water, dried over magnesium sulphate and evaporated to give trans-3-(2,2-dichlorocyclopropyl)-2,2-dimethylcyclopropa necarboxylic acid as a white solid (1.8 g, 68%) mp 114-11 70C.

Trans-3-(2,2-dichlorocyclopropyl)-2,2-dimethylcyclopropanecarboxylic acid was esterified by a method similar to that of Example 1 to give trans-3-phenoxybenzyl 3-(2,2-dichlorocyclopropyl)-2,2- dimethylcyclopropane carboxylate (7) as an oil (yield 75%) nod21.558.

Analysis: C22H22O3Cl2: C H Cl calculated: 65.2 5.5 17.5 Found: 65.8 5.7 17.2 EXAMPLES 8 AND 9 By methods similar to that of Example 2 there were prepared: 8 trans-a-cyano-3-phenoxybenzyl 3-(2,2-dichlorocyclopropyl)-2,2-di methylcyclopropa necarboxylate (yield 77 /0) oil nod31.544.

Analysis: C23H2,N 3Ct2: C H N Calculated: 64.2 4.9 3.3 Found: 63.9 5.1 4.1 9 cis-a-cyano-3-phenoxybenzyl 3-(2,2-dich lorocyclopropyl)-2,2-dimethyí cyclopropanecarboxylate (yield 70%) oil nD2' 1.554.

Analysis: C23H21NO3CI2: C H N Calculated: 64.2 4.9 3.3 Found: 64.0 5.1 3.3 EXAMPLES 10 AND 11 Preparation of 1 ScisS-/1 RcisR-a-cyano-3-phenoxybenzyl 3-(2,2-di bromocyclopropyl)-2,2dimethylcyclopropanecarboxylate (10) and 1 RcisS-ll ScisR-a-cyano-3-phenoxybenzyl 3-(2,2 dibromocyclopropyl)-2,2-dimethylcyclopropanecarboxylate (1 1) Cis-methyl 2,2-dimethyl-3-vinylcyclopropane carboxylate (1.4 g, 10 mM), phenyltribromomethyl mercury (5.3 g, 10 mM) (prepared by the method of J. Organometallic Chem. (1969) pages 21-26) and dry benzene (50 ml) were refluxed together under nitrogen for 6.5 hours.More phenyltribromomethyl mercury (1 g, 2 mM) was added and the reaction mixture was refluxed for a further 24 hours. The reaction mixture was allowed to cool, was filtered to remove solid phenylmagnesium bromide, was evaporated and the resulting brown oil was purified on a silica column using toluene as eluant to yield cis-methyl 3-(2,2-dibromocyclopropyl)-2,2- dimethylcyclopropanecarboxylate as an oil (2.0 g, 61%). This oil (2 g, 6.4 mM), 2N aqueous sodium hydroxide solution (20 ml) and ethanol (20 ml) were stirred together at ambient temperature for 1 7 hours. The reaction mixture was then diluted with water and extracted with diethyl ether. The aqueous phase was separated off, acidified with dilute hydrochloric acid and extracted twice with 20 ml portions of diethyl ether.The combined ether extracts were washed with water, dried over magnesium sulphate and evaporated to yield cis-3-(2,2-dibromocyclopropyl)-2,2-dimethylcyclopropanecarboxylic acid as a yellow solid (1.1 g, 55%) mp 108-1 100C.

Cis-3-(2,2-dibromocyclopropyl)-2,2-dimethylcyclopropanecarboxylic acid was esterified by a method similar to that of Example 2. Overall yield of cis-a-cyano-3-phenoxybe nzyl 3-(2,2 dibromocyclopropyl)-2,2-dimethylcyclopropanecarboxylate was 69% but the product was obtained from the silica column in two fractions:- 10 1 ScisS-/1 RcisR-a-cyano-3-phenoxybenzyl 3-(2,2-dibromocyclopropyí)-2,2-dimethylcyclopropane carboxylate n21 1.573.

Analysis: C23H2tNO3Br2: C H N Calculated: 53.2 4.1 2.7 Found: 53.7 4.2 3.0 11 1 RcisS-/1 ScisR--cyano-3-phenoxybenzyl 3-(2,2-dibromocyclopropyl)-2,2- dimethylcyclopropanecarboxylate nDX 1.571.

Analysis: C23H2,NO3Br2: C H N Calculated: 53.2 4.1 2.7 Found: 53.8 4.2 3.0 Pesticidal Tests The insecticidal activity of the compounds under consideration was assessed using the following pests.

Insects: Spodoptera littoralis (S.l.) Aedes aegypti (A.a.) Musca domestica (M.d.) Aphisfabae (A.f.) (i) Spodoptera littoralis (S.l.) Aqueous test formulations were made up containing 0.2% by weight of the compound to be tested, 0.05% by weight of TRITON X-1 00 (Trade Mark) wetting agent and 10% by weight of acetone.

Varying concentrations were obtained by diluting the formulations. An artificial diet mixture was prepared by dissolving, with heat, 9.6 g agar ("Oxoid No. 1" -Trade Mark) in 540 ml water, blending the resulting solution with a mixture of 1 50 g finely ground French bean seed, 24 g dried brewers yeast, 24 g ascorbic acid, 0.75 g sorbic acid, 1.5 g methyl p-hydroxybenzoate and 2.6 ml of a 10% aqueous solution of formalin, in 340 ml water, and finally mixing in 8 ml linseed oil and 7 ml of a 1% by weight aqueous solution of a mixture of vitamins consisting of by weight 5 parts nicotinic acid, 5 parts calcium pantothenate, 2.5 parts riboflavin, 1.25 parts aneurine hydrochloride, 1.25 parts pyridoxine hydrochloride, 1.25 parts folic acid, 0.1 parts D-biotin and 0.01 parts cyanocobalamine. Whilst still warm the artificial diet mixture was poured into petri dishes to give an even, thin layer just covering the base of the dish, the dishes were left to enable the diet to cool and set, and the surface of the diet was then sprayed with test formulation and allowed to dry. Each dish was then infested with ten Eyptian cotton leafworm larvae (Spodoptera littoralis). After 24 hours and again after 7 days the percentages of dead and moribund larvae were recorded.

(ii) Aedes aegypti (A.a.) The compounds to be tested were dissolved in acetone and with each solution a series of half dilutions were prepared, also using acetone. 100 microlitre samples were taken by micropipette and added to separate 100 ml volumes of water in beakers to give the required concentrations, expressed in ppm, the most concentrated solution being 3 ppm. These solutions were left for 10 minutes to allow the acetone to evaporate and then 10 early fourth instar yellow fever mosquito larvae (Aedes aegypti) were introduced into each beaker. Transparent petri dishes were placed over the beakers to prevent escape of emerging adult mosquitos. After 48 hours the mortality of the larvae was assessed and small amounts of ground Short and Gannidge No. 1 vitamin enriched animal feed pellets were added to the solutions.

Mortality was again assessed after 7 days.

(iii) Musca domestica (M.d.) Batches often 2 to 3 day old milk-fed adult female houseflies (Musca domestica) anaesthetised using carbon dioxide were placed on petri dishes lined with filter paper. The dishes were sprayed with aqueous test formulations similar to those used in (i) above using a spray machine operating on a logarithmic dilution principle. The flies were subsequently 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 onto the filter paper. Mortality was assessed after 24 hours.

(iv) Aphis fabae (A.f.) Tests were carried out on adult black bean aphids (Aphis fabae). Pairs of broad bean leaves on filter paper in petri dishes were sprayed side by side with uncounted quantities of aphids in small gauzecovered containers. After passing through the spray the aphids were tipped onto the leaves and lids were placed on the petri dishes. Mortality was assessed after 24 hours.

The results are shown in Table I in which the test species are identified by the initials noted above the the activity of the compound is expressed in the form of its Toxicity Index (to.) which is calculated from the following equation:- LC50 of ethyl parathion (standard) Toxicity Index (T.l.) = LC50 of test compound TABLE I

Toxicity Index S.l. A.a.

Test Compound 1 day 7 days 2 days 7 days M.d. A.f.

1 34 39 6 6 4 3 2 210 220- 90 100 14 42 3 270 310 50 5 42 10 4 27 36 5 3 3 B 5 170 190 54 3 44 B 6 700 750 100 4 144 18 7 54 56 8 3 21 B 8 310 390 32 5 170 7 9 336 430 41 5 800 33 10 6 9 C B 1 22 11 130 170 22 32 2 280

Claims (10)

1. A cyclopropanecarboxylate ester of formula

wherein R' and R2 are independently selected from hydrogen, fluorine, chlorine and bromine atoms, Y is hydrogen, cyano or ethynyl, and Z1 and Z2 are independently selected from hydrogen, fluorine, chlorine and bromine atoms.

2. An ester according to Claim 1 wherein Y is hydrogen or cyano, Z' is a hydrogen or bromine atom and Z2 is a hydrogen or fluorine atom provided that at least one of Z' and Z2 is a hydrogen atom.

3. An ester according to Claim 1 or 2 wherein Za and Z2 are both hydrogen atoms.

4. An ester according to Claim 1,2 or 3 wherein R1 and R2 are both hydrogen, fluorine or chlorine atoms and Y is cyano.

5. A process for preparing an ester of formula i as defined in any one of Claims 1 to 4, which process comprises reacting a compound of formula

with a compound of formula

wherein R', R2, Y, Z1 and Z2 are as defined in Claim 1, one of P and W represents a halogen atom and the other represents a hydroxy group.

6. A process according to Claim 5 wherein P is a hydroxy group and W is a halogen atom.

7. An ester according to Claim 1 substantially as hereinbefore described in any one of Examples 1 to 11.

8. A process according to Claim 5 of preparing an ester according to Claim 7 substantially as hereinbefore described in Example 1 or 2.

9. A pesticidal composition which comprises an ester of formula I as claimed in any one of Claims 1 to 4 and 7 in association with an inert carrier.

10. A method of combating pests at a locus which comprises applying to the locus an ester of formula I as claimed in any one of Claims 1 to 4 and 7 or a composition according to Claim 9.