NO149385B - 1-PHENYL-CYCLOBUTANE CARBOXYLATE COMPOUNDS WITH EFFECTS ON INSECTS (INSECTA) AND SPIDER ANIMALS (ARACHNIDA) - Google Patents

Description

The present invention relates to 1-phenyl-cyclobutane-carboxylate compounds with action against insects (Insecta)

and arachnids (Arachnida), and the peculiarity of connecting

one according to the invention is that they have the general formula (1)

wherein R<1> is lower alkoxy, tetrafluoroethoxy, fluorine, chlorine

2 12

or bromine, R is hydrogen or R and R together form a methylenedioxy group, R is one of the following groups (a) to

(f)

wherein <y>\ Y^, Y^, Y^, Y^ and Y^ are the same or different and each represents hydrogen or fluorine, bromine or chlorine, with the proviso that when R is fluorine, chlorine or bromine has at least one of Y 1 - Y 6 a meaning other than hydrogen.

The terms "Insecta" and "Arachnida" refer to the systematic class designations for arthropods. The terms "insecticide" and "insecticide action" used in the following refer to action against these classes of arthropods. It has been established by experiment that the compounds of formula (I) are active against mites.

Known compounds which may be considered related to the compounds of formula I are those in which the groups (a) to (f) are present as esterifying groups with chrysanthemic acid in commercial or experimental pyrethroids. DE-A-2,653,189 describes a similar class of esters.

DE-0-2,733,746 describes compounds of formula I in which

16 12

all groups Y to Y are hydrogen, R and R are each hydrogen, or fluoro, chloro, bromo or methyl and R<3> is one of groups (a), (c) and (e) above. These compounds are not covered by the present invention. 1 2 Preferably, R is ethoxy or propoxy and R is hydrogen. Compounds in which R 1 and R 2 form the methylenedioxy group are also preferred.

Also preferred is R 3 of the groups (a), (c) and (e) as defined above-.

It is also preferred that from one to all six of the groups

Y 1 to Y 6 is a fluorine group, with any remaining group being hydrogen. Tetrafluoro substitution (Y 1 , Y 2 ,

Y<3>, Y<4> = F; Y<5>, Y<6> = H) is particularly preferred.

Particularly preferred compounds in accordance with the invention are the following: 3<1->phenoxybenzyl-1-(3,4-methylenedioxyphenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylate and its O-cyan and o(-ethynyl -derivatives: 3<1->phenoxybenzyl-1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylate and its ct -cyan and 0^ -ethynyl derivatives.

3

The compounds of formula I in which R is one of the groups

(a) to (f) are extremely active as insecticides, with an insecticidal activity of an order of magnitude greater than most known insecticides. Certain compounds also have the property of contact repellency towards insects. The compounds according to the invention are generally more active against flies than the compounds according to the above-mentioned DE-A-2,653,189.

The compounds of formula I are optically active and can be resolved into their optical isomers by conventional methods. The invention thus encompasses the individual (+) and (-) optical isomers of the compounds as well as their racemics

(-) forms^

It is also noted that the insecticidal activities of optical isomers of compound I with R = (a) to (f) may differ by an order of magnitude or more.

The compounds I in which R is one of the groups (a) to (f) can be prepared by esterification of the free acid (formula I,

3 - 3 3

R' = H) with the appropriate alcohol R OH, wherein R is one of the groups (a) to (f). This esterification can be carried out by any suitable known method, e.g. by direct reaction or by previous conversion of the acid and/or alcohol into a suitable reactive derivative, or by an omestrin reaction between the alcohol R 3 OH (R 3 = (a) to (f) ) and a lower alkyl ester of the acid.

The acid (formula I, R 3 = H) is prepared by reaction between an appropriately substituted benzyl compound and an appropriately substituted 1,3-dihalopropane to form a 1-phenyl-cyclobutane compound which can be hydrolyzed to the acid. This reaction core is as follows:

Z represents a group that activates the benzyl methylene and itself can later be hydrolyzed to a carboxyl group, e.g. -C=N 12 12 or -COOEt; X stands for chlorine, bromine or iodine; R , R , Y , Y , Y<3>, Y^, Y~* and Y^ are defined as above. An alternative preparation method for the acid (formula I, R 3=H) as 12 3 4's lower alkyl ester is by adding the olefin Y Y C=CY Y to the substituted phenyl acrylic ester of formula II

wherein R is a lower alkyl group and R1, R2, Y<1>, Y<2>, Y<3>, Y4, Y<5> and Y^ have the above meaning.

Esters of formula I (R<3>= lower alkyl) in which Y<3>=Y<4>=F and

12 5 6

Y =Y =Y =Y =H can be produced by first and produce

3 4 12

the compounds in which Y =Y =F, Y =Y =C1 in accordance with the preceding method (using dichlorodifluoroethylene) and subsequent hydrogenation of the product to replace the chlorine groups with hydrogen.

The esters II in which Y^=Y^=H can be prepared by the following general methods: (1) A lower alkyl ester of the appropriately substituted phenylacetic acid (V) is condensed with a dilower alkyl oxalate in the presence of a basic catalyst to prepare the enolate salt (IV). (2) The solution of the enolate salt is acidified to give the corresponding phenyl oxaloacetate (III). (3) The compound III is reacted with formaldehyde under alkaline conditions to give the phenyl-hydroxymethyl acetate which on dehydration (sometimes spontaneously) gives the phenyl acrylic ester (II).

This reaction sequence is illustrated in the following overall reaction scheme. It will be understood that the specific acids and bases indicated may be replaced by other suitable compounds. Lower alkyl esters other than the ethyl esters as shown can also be used.

When Y 5 =Y 6 =F, the esters II can be prepared using the method described by D.G. Naae and D.J. Burton, Synthetic Communications, 3, 197-200 (1973). In this method, the appropriate phenyl j:o ester of formula VI is reacted with dibromodifluoromethane (CBr 2 F 2 ) in the presence of 2 mol of tris (dimethylamino)phosphine and a suitable solvent such as e.g. diglyme or triglyme

wherein Ph has the above meaning and R is a lower alkyl group.

The general method of forming the esters according to the invention is as follows: "where A is

Wherein R1, R<2>, Y<1>, Y<2>, Y<3>, Y<4>, Y5 and Y6 have the above meaning and R 3 is one of the groups (a) to (f) set forth above .

Alternatively, the ethyl ester can be converted directly as follows:

The novel compounds described herein can be dissolved in a suitable organic solvent, or a mixture of solvents, to form solutions or brought into aqueous suspension by dispersing organic solvent solutions of the compounds in water, to give useful liquid compositions, such as can be incorporated into dispersions of the aerosol type with the usual aerosol propellants.

The compounds may also be incorporated into solid preparations which may include inert solid diluents or carriers, to form useful solid preparations. Such mixtures can also include other substances such as e.g. wetting agents, dispersing agents or adhesives, and may be prepared in granular or other forms to provide slow release of the compounds over an extended period of time. The compounds may be used in such preparations either as the sole toxic agent or in combination with other insecticides, such as . pyrethrum, rotenone, or with fungicidal or bactericidal agents, to provide preparations useful for household and agricultural dusting preparations and pesticides, textile coating and impregnation agents, and the like..

In particular, Ae new compounds can advantageously be combined with other substances that have a synergistic or potentiating effect. In general, such substances are of the class of microsomal ox/dase inhibitors, i.e. they prevent the detoxification of the insecticides in insects produced by the action of oxida -tive enzymes.. Typical substances of this type are the pyrethrin synergists of which the following are. examples:

("Sesoxane", "Sesamex" and "Sulphoxide" are brand names)...

"Sesoxane" (manufactured by Shulton Inc., Clifton, N.J., USA) has been found to be particularly useful as a potentiator. The amount of "Sesoxane" used can vary from 1/1000 to five times the weight of compound I, the preferred range being from 1/100 to equal parts by weight. Piperpnyl butoxide is also a useful potentiator in similar amounts.

The production and properties of the compounds according to the invention are illustrated by means of the following specific examples.

EXAMPLE 1 (Comparison example)

(a) 1-(4-Chlorophenyl)cyclobutanenitrile

4-chlorobenzyl cyanide (10 g) in dry DMSO (20 ml) was added over 5 min. to a stirred suspension of sodium hydride (4.4 g) in DMSO at 25°C under argon. The mixture was stirred in-..

30 min. and then a solution of .1,3-dibromopropane (27 g) in dry DMSO (50 ml) was added over the course of 30 min. while the temperature of the reaction mixture was maintained at 25 - 30°C. After stirring

another 40 min. at this temperature the reaction mixture was added to ice-water (500 ml) and extracted with dichloromethane (3 x 75 ml). The extracts were evaporated and the residue extracted with diethyl ether (4 x 50 ml). The other extracts were washed with water, dried over anhydrous sodium sulfate and evaporated to give an oil (10.8 g) which on distillation gave the nitrile (boiling point 90°C/ 10~<6> Torr ) Yield 5.4 g (43 %).

Analysis: C 68.48%, H 5.49%, Cl 18.3%, C^H^Cl N

theoretically requires: C 68.93%, H 5.25%, Cl 18.5%.

(b) 1-(4-Chlorophenyl)cyclobutanecarboxylic acid

1-(4-Chlorophenyl)cyclobutanenitrile (5 g) was mixed with ethylene glycol (60 mL) and 40% w/w aqueous potassium hydroxide solution (80 mL) and boiled under argon for 18 h. The mixture was cooled, added to ice water and extracted with diethyl ether. The aqueous layer was acidified and the precipitate was filtered off, washed with water, dried and recrystallized from petroleum ether (boiling point 40 - 60°C) to give the acid as white needles of m.p. 88 - 89°C, yield 4.5 g (82%).

Analysis: C 62.70%, H 5.14%, Cl 16.5%. 0 15-, 2% Cj^H^CLC^

theoretically requires C 62.72%, H 5.26%, Cl 16.83%, O 15.2%.

(c) 3'-phenoxybenzyl-1-(4-chlorophenyl)cyclobutanecarboxylate

1-(4-Chlorophenyl)cyclobutanecarboxylic acid (1 g) was dissolved in thionyl chloride (1 ml) and heated under reflux for 40 min. Excess thionyl chloride was removed under vacuum and the residue was taken up in petroleum ether 40 - 60°C (40 ml) and added over the course of 15 min. to a stirred mixture of 3-phenoxybenzyl alcohol (1.1 g), pyridine (1 ml), benzene (50 ml) and petroleum ether 40 - 60°C

(50 ml) maintained at 10°C. The mixture was stirred by

20 - 25°C for 3 hours and then added to ice-mixed water,

washed with 0.5M hydrochloric acid, water, dilute sodium bicarbonate solution and dried over anhydrous. sodium sulfate. The solvent was evaporated to give an oil (2.3 g) which after chromatography on silica gel, eluting with benzene/petroleum ether, gave the ester 1.52 g (82%).

Analysis: C 72.87%, H 5.30%, Cl 9.2%, O 12.1%.

C24H21C103 theoretically requires: C 73.37%, H 5.39%, Cl 9.0%, O 12.2%.

EXAMPLE 2

(a) 1-(4- ethoxyphenyl) cyclobutane carboxylic acid

Ethyl 4-ethoxyphenyl acetate (14 g) in anhydrous diethyl ether (20 ml)

was added to a stirred suspension of sodium amide (5.3 g) in liquid ammonia (400 ml) over 3 min. and the mixture stirred for a further 20 min. 1,3-dibromopropane (14 g) in diethyl ether (10 ml) was added over 20 min. and the mixture stirred for 17 hours. 50 ml of saturated ammonium chloride solution was added and the reaction mixture was extracted with diethyl ether. Evaporation of the solvent gave a residue (17.4 g) which after chromatography on silica gel by elution with benzene/chloroform gave an oil (7.2 g). The oil was dissolved in ethanol (50 mL) and 10% sodium hydroxide solution (50 mL) was added. The mixture was refluxed for 3 hours, cooled, added to ice-water and extracted with diethyl ether. The aqueous layer was acidified and the precipitate was filtered off, washed with water, dried and recrystallized from petroleum ether 40 - 60°C to give the acid 5.2 g (35%) m.p. 90 - 91°C.

Analysis: c'"71'.04%, H 7.23%, 0 22.0%

C13H16°3 theoretically required C 70.89%, H 7 ,' 32%, O 21.8%."

(b) 3'-phenoxybenzyl-1-(4-ethoxyphenyl)cyclobutanecarboxylate

1-(4-Ethoxyphenyl)cyclobutanecarboxylic acid (1 g) was refluxed in thionyl chloride (1 ml) for 30 min. and excess thionyl chloride removed under vacuum. The residue was taken up in petroleum ether 40 - 60°C (25 ml) and added over the course of 5 min. to a stirred mixture of 3-phenoxybenzyl alcohol (1.1 g) pyridine (1 ml)

benzene (25 ml) and petroleum ether 40 - 60°C (25 ml) at 15°C.

The mixture was stirred at 15°C for 3 hours and then added

to ice-water and extracted with diethyl ether. The extract was washed with water, 0.5M hydrochloric acid, and sodium bicarbonate solution and then dried over anhydrous sodium sulfate and the solvent removed to give an oil (2.1 g). Chromatography on

silica gel, elution with benzene gave the ester (1.5 g) (82%).

Analysis: C 77.55%, H 6.65%, O 16.0%

C26H26°4 theoretically requires C 77.59%, H 6.51%, O 15.9%.

EXAMPLE 3

(a) 2- (4-ethoxy enyl) propenic acid.- ethyl ester

This part of the example shows it. general method to

prepare the 2-aryl acrylic acid esters. (Formula II).

Alcohol-free sodium ethoxide freshly prepared from sodium (13.9 g)

and excess ethanol was slurried in dry benzene (200 mL).

To this suspension, diethyl oxalate (88.5 g) was added in the batch

of 15 min.- Ethyl p-ethoxyphenyl acetate (V) (114.2 g) was added to the resulting clear yellow solution over the course of 30 min. at room temperature. After a further 1 hour, the reaction mixture solidified. The solid sodium diethyl 2-p"-ethoxyphenyl-3-ethoxy-3-oxido-oxaloacetate (IV) was triturated and washed well with ether.

The combined ether extracts were evaporated to a further small volume

to give an additional amount of salt.

The total yield was 227.4 g.

The sodium salt was acidified by adding it in portions to

a well-stirred emulsion of equal parts diethyl ether and dilute acetic acid (about 10%). After separation, the ether layer was washed with water and dilute sodium bicarbonate solution and dried with anhydrous sodium sulfate. After evaporation of the ether, the remaining oil was crystallized from petroleum ether (boiling point 60 - 80°C) to give diethyl 2-p-ethoxyphenyl oxaloacetate (III)

(143.8 g) (85%), m.p. 59 - 60°C.

The keto ester III (143.8 g) was stirred in dilute formaldehyde solution (62 ml 37% formaldehyde + water 220 ml) and to the suspension potassium carbonate solution (54.5 g in water 280 ml) was added dropwise. At the end of the addition, ether was added to it. stirred the suspension to dissolve the gummy precipitate that had formed and after a further 15 min. gas development began. When this gas evolution ceased (after about 2 hours), the reaction mixture was extracted with additional ether and the combined ether extracts were washed with water and evaporated after drying over Na 2 SO 4 . The yield of ethyl 2-(4-ethoxyphenyl)propenoate (ii) (isolated as a yellow oil) was 97.8 g (79.8%). (b) et/ 1- 1-( 4- ethoxyphenyl)- 2, 2, 3, 3- tetrafluorocyclobutanecarboxylate •

2-(4-Ethoxyphenyl)propenoic acid ethyl ester (13.2 g) was mixed with benzene (7.5 ml), α-pinene (2 drops;) N-ethyldiisopropylamine (2 drops) and tetrafluoroethylene ( 15.5 ml) and heated to 150 - 155°C for 24 hours and then at 155 - 160°C for 17 hours. After evaporation of volatile materials, the residue (16.6.g) was dissolved in dichloromethane and chromatographed on a column of ... silica gel to give the ester as a colorless oil 14.5 g (75%). Analysis: C 56.47%, H 5.24%, F 23.4%.

<C>15H16<F>4°3 theoretically requires C 56.2 5%, H.5.04%, F 2-3.7%..•

(c) i-(4-ethoxy/phenyl)-2,2,3,3-tetrafluorocyclobutane-carboxylic acid

Ethyl 1-(4-ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutane carboxylate (14.5 g) was dissolved in ethanol (100 mL) and a 10% w/w solution of sodium hydroxide in water (100 mL) was added and the mixture refluxed for 2.5 hours. The mixture was cooled, added to ice water and extracted with diethyl ether. The aqueous layer was acidified and the precipitate was filtered off, washed with water, dried and crystallized from 50-80°C petroleum ether to give the acid with m.p. 112 - 113°C. Yield 11.2 g. (85%).

Analysis: C 53.20%, H 4.22%, F 25.9%.

C13H12F4°3 theoretically requires C 53.43%, H 4.14%, F 26.0%.

(d) 3'-phenoxybenzyl-1-(4-ethoxyphen/l)-2,2,3,3- tetrafluorocyclobutanecarboxylate

1-(4-Ethoxyphenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylic acid (0.9 g) was refluxed with thionyl chloride (1 ml) for 45 min. and excess thionyl chloride was removed under vacuum. The residue was dissolved in petroleum ether 40 - 60°C (40 ml) and added over the course of 5 min. to a mixture of 3-phenoxybenzyl alcohol

(1 g) pyridine (1 ml), benzene (2 5 ml), and petroleum ether 40 - 60°C

(25 ml) kept at 20°C. The mixture was stirred for 3 hours and then added to ice-water and extracted with diethyl ether. The extract was washed with water, 0.5M hydrochloric acid and sodium bicarbonate solution, dried over anhydrous sodium sulfate and the solvent evaporated to give an oil (2 g). Chromatography on silica gel eluting with benzene gave the ester 1.2 g (82%).

Analysis: C 65.45%, H 4.84%, F 16.0%..

<C>26<H>22<F>4°4 theoretically requires C 65.82%, H 4.67%, F 16.0%..

EXAMPLE 4

(a) (-) enantiomer of 1-(4- ethoxyphenyl)- 2, 2, 3, 3- tetrafluoro-cyclobutane- carboxylic acid

α(+)-(1-Naphthyl)ethylamine was added to a solution of the racemic acid (2g) (prepared as in Example 3(c)) in ethyl acetate (75ml) and n-hexane. The salt formed was crystallized four times from ethyl acetate at room temperature. The (+) (-) salt was cleaved with hydrochloric acid (1M) and the residue recrystallized twice from ethanol. The (-) acid had cx^q = -118.2 and m.p. 194°C and was obtained in 15% yield.

(b) (-) 3'-phenoxybenzyl- 1-(4- ethoxyphenyl)- 2, 2, 3, 3- tetrafluorocyclobutane- carboxylate

The isolated (-) acid, 0.2 g, was refluxed in thionyl chloride (1 mL) for one hour. After evaporation of excess thionyl chloride, the residue was dissolved in petroleum ether (boiling point 60 - 80°C) and added to 3-phenoxybenzyl alcohol (0.139 g) and pyridine (0.238 g) in benzene (3 ml) and petroleum ether (3 ml). The reaction mixture was stirred overnight, quenched with ice water, washed with water and the solvent layer separated and dried over a molecular sieve. After evaporation of the solvent, the pure ester was obtained as a viscous liquid by chromatography on silica gel using methylene chloride as eluent. Yield 99.1%, a<®>Q = -58v2.

EKS EMPEL" 5

(a) 1-(3,4-methylenedioxyphenyl)-2,2,3,3-tetrafluorocyclobutanecarboxylic acid

A mixture of ethyl 2-(3,4-methylenedioxyphenyl)propenoate (2.2 g), tetrafluoroethylene (5 ml), -t-pinene (1 drop), N-ethyldiisopropylamine (1 drop) and benzene (10 ml) was heated at 150 - 155°C

for 24 hours and then at 160 - 165°C for 16 hours and then cooled. The solvent was evaporated leaving an oil (3.0 g).

This oil was purified by chromatography on silica gel using benzene as an eluent to give 1.4 g (44%) of ethyl 1-(3,4-methylene-dioxophenyl)-2,2,3,3-tetrafluorocyclobutane- carboxylate.

The ethyl ester was hydrolyzed by refluxing

2 hours with a mixture of potassium hydroxide (5 g), water (50 ml) and ethanol (50 ml). Ethanol was removed by evaporation and the aqueous residue extracted with diethyl ether. The aqueous layer was acidified and the precipitate filtered off, dried and recrystallized from petroleum ether' (boiling point 60 - 80°)/diethyl ether to give 0.9 g of the acid as white crystals of m.p. 168 - 169°C.

Analysis: C 49.62%, H 2.72%, F 25.8%.

C12H8F4°4 theoretically requires C 49.33%, H 2.76%, F 26.0%.

(b) 3' phenoxybenzyl-1-(3,4-methylenedioxyphene/1)-2,2,3,3-tetrafluoroc/clobutane-carboxylate

The acid prepared in Example 5(a) (0.5 g) was mixed with thionyl chloride (1 ml) and refluxed for 45 min. Excess thionyl chloride was removed under vacuum. The residue was dissolved in petroleum ether (boiling point 40 - 60°) (5 ml) and added over the course of 5 min. to a stirred mixture of 3-phenoxybenzyl alcohol (0.4 g), pyridine (0.5 ml), benzene (15 ml) and petroleum ether (boiling point 40 - 60°) (15 ml). After stirring overnight at room temperature, the mixture was added to ice-water and extracted with diethyl ether. The ether extract was washed with dilute hydrochloric acid, water, sodium bicarbonate solution and dried over anhydrous sodium sulfate. Evaporation of ether left an oily residue (0.78 g) which was purified by chromatography on silica gel eluting with benzene to give 0.7 g of the 3-phenoxy-benzyl ester as a clear yellow oil.

Analysis: C 63.54%, H 4.01%, F 15.9%.

C25<H>18<F>4°5 theoretically requires C 63.30%, H 3.82%, F 16.0%.

EXAMPLES 6 to 2 0

By applying the general method indicated in Example 3, the following compounds reproduced in Table 1 were obtained from the corresponding starting materials.

Elemental analysis, spectra and other characterizing data were consistent with the stated structures.

Table 1 includes the compounds from examples 1, 2, 3, 4 and 5 for an easier overview.

EXAMPLE 21

The biological activity of the new cyclobutane esters was investigated in a series of tests with results collected in the following table 2.

Insecticidal activity was investigated against the common housefly, Musea domestica, and the sheep fly, Lucilia cuprina. The methods used were as follows:

(i ) Houseflies

(a) The compound alone

Experiments were carried out using a standard DDT-susceptible strain (WHO/IN/1) of M. domestica. The compound was administered in acetone solution by means of a micro-needle to the dorsum of the thorax of 2 day-old female flies bred from the pupal stage with an average weight of 2.2 - 2.5 g/100 pupae. The adult flies were administered water and a diet of sugar alone and maintained at 26°C and 70% relative humidity. Mortality was determined 48 hours after treatment and compared to acetone-treated control animals. Flies unable to move or stand normally were considered dead. LD^Q- value was obtained from a calculator program based on three groups of 10 flies at each dosage level.The LD^Q value for DDT determined under the same conditions was 0.26 pg/fly.

(b) Potentiation

The compound was also tested on insects described above in connection with the potentiator "Sesoxane" by pre-treating the insect with 1 µg of the potentiator in acetone.

Mortality was determined 48 hours after treatment and compared with acetone and acetone/potentiator controls.

LD^Q value was determined as described above.

For DDT, with the same potentiator, the LD5Q value was 0.24 pg/fly.

Approximately the same levels of potentiation were obtained when "Sesoxane" was replaced with an equal amount of piperonyl butox yd.

(c) Insect repellent

Repellency tests were carried out with the same strain of houseflies as in the lethality tests. Female flies that were at least 2 days old, which had not previously been fed protein, were anesthetized with CO2 on the day of the test and counted in containers each containing 20 flies. These were supplemented with water and solid sucrose. On the test day, food and water were removed in the morning (09:00). When the tests were carried out only between 12.00 and At 17.30 the flies were therefore kept fasting for at least 3 hours for the testing.

The test involves the use of attractants to which the test compound was applied. These were exposed to the flies and the number of flies that landed on each lure was noted. The baits consisted of aluminum shells with an area of 5.94 cm 2 filled with common bridging yeast mixed with water and heated to produce a solid surface film.

Each group of 20 flies was used in an experiment where 7 dishes were treated with a graded dilution series of the test compound using acetone as solvent, along with one dish treated with acetone as a control. The concentration of the compound ranged from 0.031 pg/µl which doubled at each level up to 2.0 µg/µl. One hundred microliters of each solution was pipetted evenly over the surface of each dish and left until the acetone had evaporated.

The flies used were released into dandard

205 mm x 205 "mm x 255 mm wire mesh cages and allowed to acclimatize in the test room maintained at a temperature of 2 6°C + 1°C and humidity approximately 60%, for 10 min. for the

treated bowls were quickly inserted into each cage. For use, the bowls were marked on the back and then randomly mixed to avoid certain tendencies in the judgement. At the 30 min. test "the number of flies on the surface of each dish was noted in the first and second minutes after the introduction of the baits and then every other minute. In this way sixteen counts were made for each concentration, the sum of these being used for a regression analysis of concentration effect. A total count of the landings for each concentration was also obtained and used for the calculation of repellency index (IR). All relevant tests were carried out with fresh flies and lures, and the compounds were treated in three replicate groups.

The total number of flies recorded for each dish for those

seven concentration levels were summarized and averaged. In the following formula, this designation is indicated by (N), where

(C) indicates the number of flies noted on the control:

(ii) Sheep flies

(a) Insecticidal action

The compounds were tested for activity against a dieldrin-tolerant strain (LBB) that had been collected for dieldrin use in the field.

The test compound was applied in acetone solution, 0.5 µl distributed with a Drummond micropipette to the dorsum of the thorax of 2-3 day old female flies. Adult flies were supplied with water and sugar alone kept at 25°C and 60 - 70% RH. Mortality was determined after 24 hours. Restless flies were considered dead. The LD^ values, on a concentration basis, were interpolated from a graphical representation using a computer program. Comparative LD^ figures for DDT and dieldrin are 0.17 respectively. 0.025 ug/insect.

(b) EoteQtiering

Potentiation with "Sesoxane" was examined as described above in the housefly tests.

(c) Assistance

Repulsion was determined as described above in the housefly tests, with the exception that the baits consisted of an agar gel containing fresh bovine blood.

The test methods are described in BRD Offenlegungsschrift No. 2,653,189 published on 8 June 1977, see e.g. 38 in (c)

(house flies) and 38 iii(c) (sheep flies).

Claims (11)

1. 1-phenyl-cyclobutane-carboxylate compounds with effect against insects (insecta) and arachnids (Arachnida) characterized by the fact that they have the general formula (i) in which R is lower alkoxy, tetrafluoroethoxy, fluorine, chlorine 2 12 or bromine, R is hydrogen or R and R together form a methylenedioxy group, R 3 is one of the following groups (a) to (f) wherein y\ Y<2>, Y<3>, Y<4>, Y^ and Y 6 are the same or different and each represents hydrogen or fluorine, bromine or chlorine, with the proviso that when R -) is fluorine, chlorine or bromine, at least one of Y 1 - Y 6 has a meaning other than hydrogen. 2. Compound as stated in claim 1, characterized in that R is ethoxy or propoxy. 3. Compounds as stated in claim 1, characterized in that R<3> is one of the groups (a), (c) and (e). 4. Compounds as stated in claims 1-3, characterized in that from one to all six 1 6 of the groups Y to Y is a fluorine group, with any remaining groups being hydrogen. 5. Compounds as stated in claim 4, 12 3 4 characterized in that Y , Y , Y and Y all 5 6 is fluorine and Y and Y is hydrogen. 6. Compounds as stated in claim 1, characterized in that they consist of the (+), (-) and (-) forms of 3'-phenoxybenzyl-1-(3,4-methylenedioxy-phenyl)-2,2,3 ,3-tetrafluorocyclobutane carboxylate. 7. Compounds as stated in claim 1, characterized in that they consist of the (+), (-) and (-) forms of ©C-cyano-3'-phenoxybenzyl-1-(3,4-methylenedioxy-phenyl) -2,2,3,3-tetrafluorocyclobutane carboxylate. 8. Compounds as set forth in claim 1, characterized in that they consist of the (+), (-) and (-) forms of O^-ethynyl-31-phenoxybenzyl-1-(3,4-methylenedioxy-phenyl)- 2,2,3,3-tetrafluorocyclobutane carboxylate. 9. Compounds as stated in claim 1, characterized in that they consist of the (+), (-) and (-) forms of 3'-phenoxybenzyl-1-(4-ethoxyphenyl)-2,2,3, 3- tetrafluorocyclobutane carboxylate. 10. Connections as stated in claim .1, characterized by. that they are constituted by the ( + ), (-) and (-) forms of °^-cyano-3'-phenoxybenzyl-1-(4-ethoxy enyl)-2 , 2 , 3 , 3-tetrafluorocyclobutane- carboxylate 11. Compounds as stated in claim 1, characterized in that they consist of the (+), (-) and (-) forms of oC_ethynYl~3'-phenoxybenzyl-1-(4-ethoxyphenyl)-2,2,3, 3-tetrafluorocyclobutane carboxylate.