GB1604450A

GB1604450A - Derivatives of cyclopropanecarboxylic acids

Info

Publication number: GB1604450A
Application number: GB4845477A
Authority: GB
Original assignee: National Research Development Corp UK; National Research Development Corp of India
Current assignee: National Research Development Corp UK; National Research Development Corp of India
Priority date: 1977-11-21
Filing date: 1977-11-21
Publication date: 1981-12-09
Also published as: JPS5495560A; DE2849942A1; FR2409261A1; FR2409261B1

Description

(54) IMPROVEMENTS RELATING TO DERIVATIVES OF CYCLOPROPANECARBOXYLIC ACIDS (71) We, NATIONAL RESEARCH DEVELOPMENT CORPORATION, a British Corporation established by Statute of Kingsgate House, 66/74, Victoria Street, London SW1, 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:- This invention relates to new derivativcs of cyclopropanecarboxylic acids, particularly useful as insect knock-down agents, to processes for their preparation, to compositions containing them and to their use in controlling infestation by insects and other pests.

Our U.K. Patent No. 1,413,491 describes and claims compounds of the general formula:

in which R2 and R1 may represent, inter alia, halogen and R may represent, inter alia, a tetrahydrophthalimidomethyl group.

Compounds of formula I can exist in the form of geometrical isomers depending upon whether the hydrogen atoms carried at Cl and C3 of the cyclopropane ring are in the cis or trans relationship. Because of the unsymmetrical substitution at C1 and C, on the cyclopropane ring, each cis isomer can exist in one of two optically active forms and each trans isomer can exist in one of two optically active forms. When the absolute configuration at Cl of compounds of formula I is the same as that at C1 in (+)trans chrysanthemic acid, the absolute configuration of C1 in compound I is designated 1R.

The absolute configuration of C, in compounds of formula I cannot very independently of the C1 configuration in a compound having specified geometrical configuration and, for a compound having trans configuration and R configuration at Cl, strict application of the sequence rule (Cahn, R. S., Ingold C. and Prelog V. Angew. Chem. Int. Ed.

5,385 (1966)) requires the designation S to be applied at C3. However, application of the same sequence rule to the same C3 centre in (+)trans chrysanthemic acid requires that centre to be designated R, even though it is directly related in absolute configuration to the configuration designated S in compounds of formula I. This is because the nature of the substitution at C3 is different in ( T )-trans chrysanthemic acid from that of compounds of formula I. However, because the specification of the geometrical configuration and the absolute configuration at Cl fixes the C3 configuration absolutely, and to avoid possible confusion arising from the fact that different compounds of the same series may otherwise require sometimes R, sometimes S, designations of the configuration at C, we have proposed the nomenclature [lR,trans] for such compounds as this Drovides sufficient information to determine the absolute configuration of the whole molecule.

Similar considerations have resulted in our designating compounds having the same absolute configuration as (+ ) -cis chrysanthemic acid as [1R,cis] compounds.

In Example 18 of the Specification of our U.K. Patent No. 1,413,491, we describe a tetrahydrophthalimidomethyl ester of 3 - (2,2 - dichlorovinyl) - 2,2 - dimethylcyclopropane - carboxylic acid which is a racemic mixture of the two isomers having trans configuration of the hydrogens at C1 and C, on the cyclopropane ring.

We have now been able to prepare individual isomers of the tetrahvdronhthalimidomethyl esters which have surprisingly been found to have a particularly good knock-down effect towards houseflies as well as being lethal to the insects and other arthrapods.

The present invention provides an individual isomer of the general formula:

wherein R2 and RS, which may be the same or different, are each halogen, in which the hydrogen atoms at C1 and C3 of the cyclopropane ring are substantially completely m the cis configuration or substantially completely in the trans configuration and in which C1 of the cyclopropane ring is substantially completely in the absolute R configuration, the isomer being substantially free from isomers having other configurations.

In the isomers of the present invention, it is preferred that R2 and R3 both represent the same halogen and isomers wherein R2 and R3 both represent fluorine are preferred.

The individual isomers of the present invention may be prepared by esterifying tetrahydrophthalimidomethyl alcohol or an esterifiable derivative thereof with the selected isomer of 3 - (2,2 - dihalovinyl) - 2,2 - dimethylcyclopropane - carboxylic acid or an esterifiable derivative thereof. These esterification techniques are described more fully in the Specification of our U.K. Patent No. 1,413,491 and normally involve the esterification of the alcohol with an acid or acid chloride or reaction of a silver or triethylammonium salt of the carboxylic acid with a tetrahydrophthalimidomethyl halide, or by transesterification reacting a lower alkyl ester of the carboxylic acid with the alcohol.

The individual isomers of the cyclopropane-carboxylic acid or esterifiable derivative thereof can be prepared by the techniques described in the Specification of U.K.

Patent No. 1,413,491. Essentially, these involve converting the selected R isomer or isomer mixture of chrysanthemic acid by ozonolysis to form the corresponding isomer of caronaldehyde and reacting this aldehyde with the selected phosphorane of formula:

wherein R2 and R3 are as defined above and Ph represents phenyl.

The preparation of the [1R,cis] and [lR,trans] acid wherein R2 and R1 represent bromine, is described in Examples 27 and 28 respectively of the Specification of U.K.

Patent No. 1,413,491, while Examples 15 and 17 of the same Specification describe the preparation of the [1R,transj acid in which R2 and R3 each represent chlorine. The preparation of the [1R,cis] isomer of the acid in which R2 and R9 each represent chlorine is described in Example 3 of the Specification of U.K. Patent No. 1,448,228, while Example 2 of the same Specification describes the preparation of the [1R,cis] and [1R,trans} isomers of the acid in which R2 and R3 each represent fluorine.

One or more of the individual isomers of the present invention may be formulated with an inert carrier or diluent to give a composition which can be used to combat infestation by insects or other pests. The compositions may be prepared as dusts or granular solids, wettable powders, emulsions, emulsifiable concentrates, sprays, aerosols and other liquid preparations after the addition of appropriate solvents, diluents and surface active agents. The compositions may also contain other pesticidal compounds, for example to improve insecticidal activity.

The following Example is given to illustrate the invention. Tetrahydrophthalimidomethyl alcohol was esterified by the procedure described in Example 17 of the Specification of U.K. Patent No. 1,413,491 using the [1R,cis] or [1R,trans] isomer of 3 - (2,2 - difluorovinyl) - 2,2 - dimethylcyclopropane - carboxylic acid chloride prepared by reacting the acid (obtained as described in Example 2 of the Specification of Ú.K. Patent No. 1,448,228) with thionyl chloride. The resulting [1R,trans] and [lR,cis] were designated DP870 and DP891 respectively. DP870 has nD20 1.5015 DP891 is a colourless crystalline solid mp 97--99"C. These esters were tested for their knock-down effect upon houseflies using a modified Kearns and March technique. The basic techniuqe (c.f. Soap, 19 page 101 and 128 (1943)) was modified by using a chamber having 2 sprayers at each end, each discharging 1 ml. of test solvent every 5 seconds. 0.1 ml of a known solution of test compound was introduced into each sprayer and 200 flies were introduced. The test compound was sprayed for 5 seconds and knock down counts taken at 1 minute intervals for 10 minutes. From these results KDao values were calculated. For comparative purposes, similar tests were carried out using natural pyrethrin (25% w/w pyrethrum extract) and bioallethrin when the following results were obtained: % conc. giving KD,, of 4 mins.

DP 870 0.04 DP 891 0.014 Pyrethrins 0.032 Bioallethrin 0.054 The knock-down effect against cockroaches was shown in the following tests. The compound under test was dissolved in odourless kerosene and sprayed on male Blattella germanic at various concentrations. The KD-o at 5 minutes for the com- pounds were calculated to be as follows: DP 870 .0057% w/v Bioallethrin .064 % w/v S-Bioallethrin .033 % w/v Insecticidal properties of the compounds were shown in the following test. A mixed population of male and female M. domestica were sprayed in a Kearns and March chamber with a solution of a compound in odourless kerosene. The toxicity in terms of LD50 was calculated for the following compounds: LD.54 g/female .09 DP 870 .04 DP 870 + piperonyl butoxide .04 (1:5 w/w) .022 permethrin WHAT WE CLAIM IS: 1. An isomer of the general formula:

wherein R2 and R3, which may be the same or different, are each halogen, in which the hydrogen atoms at C1 and C, of the cyclopropane ring are substantially completely in the cis configuration or substantially completely in the trans configuration and in which

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

Claims

**WARNING** start of CLMS field may overlap end of DESC **. and other liquid preparations after the addition of appropriate solvents, diluents and surface active agents. The compositions may also contain other pesticidal compounds, for example to improve insecticidal activity. The following Example is given to illustrate the invention. Tetrahydrophthalimidomethyl alcohol was esterified by the procedure described in Example 17 of the Specification of U.K. Patent No. 1,413,491 using the [1R,cis] or [1R,trans] isomer of 3 - (2,2 - difluorovinyl) - 2,2 - dimethylcyclopropane - carboxylic acid chloride prepared by reacting the acid (obtained as described in Example 2 of the Specification of Ú.K. Patent No. 1,448,228) with thionyl chloride. The resulting [1R,trans] and [lR,cis] were designated DP870 and DP891 respectively. DP870 has nD20 1.5015 DP891 is a colourless crystalline solid mp 97--99"C. These esters were tested for their knock-down effect upon houseflies using a modified Kearns and March technique. The basic techniuqe (c.f. Soap, 19 page 101 and 128 (1943)) was modified by using a chamber having 2 sprayers at each end, each discharging 1 ml. of test solvent every 5 seconds. 0.1 ml of a known solution of test compound was introduced into each sprayer and 200 flies were introduced. The test compound was sprayed for 5 seconds and knock down counts taken at 1 minute intervals for 10 minutes. From these results KDao values were calculated. For comparative purposes, similar tests were carried out using natural pyrethrin (25% w/w pyrethrum extract) and bioallethrin when the following results were obtained: % conc. giving KD,, of 4 mins. DP 870 0.04 DP 891 0.014 Pyrethrins 0.032 Bioallethrin 0.054 The knock-down effect against cockroaches was shown in the following tests. The compound under test was dissolved in odourless kerosene and sprayed on male Blattella germanic at various concentrations. The KD-o at 5 minutes for the com- pounds were calculated to be as follows: DP 870 .0057% w/v Bioallethrin .064 % w/v S-Bioallethrin .033 % w/v Insecticidal properties of the compounds were shown in the following test. A mixed population of male and female M. domestica were sprayed in a Kearns and March chamber with a solution of a compound in odourless kerosene. The toxicity in terms of LD50 was calculated for the following compounds: LD.54 g/female .09 DP 870 .04 DP 870 + piperonyl butoxide .04 (1:5 w/w) .022 permethrin WHAT WE CLAIM IS:

1. An isomer of the general formula:

C1 of the cyclopropane ring is substantially completely in the absolute R configuration, the isomer being substantially free from isomers having other configurations.

2. An isomer according to Claim 1 wherein R2 and Rs each represent the same halogen.

3. An isomer according to Claim 1 or 2 wherein the halogen is fluorine.

4. 3,4,5,6 - Tetrahydrophthalimidomethyl [lR,cis] - 3 - (2,2 - difluorovinyl)2,2 - dimethyl cyclopropane carboxylate.

5. 3,4,5,6 - Tetrahydrophthalimidomethyl [lR,trans] - 3 - (2,2 - difluorovinyl)2,2 - dimethyl cyclopropane carboxylate.

6. A method of preparing an isomer according to any one of the preceding claims which comprises esterifying 3,4,5,6 - tetrahydrophthalimidomethyl alcohol or an esterifiable derivative thereof with the desired isomer of the 3 - (2,2 - dihalovinyl) - 2,2dimethylcyclopropane carboxylic acid or esterifiable derivative thereof.

7. A method according to Claim 6 wherein (a) the alcohol is reacted with the acid or acid chloride or (b) a 3,4,5,6 - tetrahydrophthalimidomethyl halide is reacted with a silver or trialkylammonium salt of the acid or (c) the alcohol is reacted with a C1-C4 alkyl ester of the acid.

8. A method according to claim 6 substantially as hereinbefore described with reference to the Example.

9. An isomer of formula II obtained by a method according to any one of Claims 6--8.

10. A composition for combatting pest infestation comprising an isomer as defined in any one of Claims 1-5 or 9 together with an inert diluent or carrier.

11. A composition according to Claim 10 including a further arthrapodicidal compound.

12. A composition according to Claim 10 or 11 including a compound which synergises the activity of pyrethrins or synthetic pyrethroids.

13. A composition according to any one of Claims 10--12 substantially as hereinbefore described.

14. A method of combatting pest infestation which comprises applying to the pest or to an environment susceptible to pest infestation an isomer according to any one of Claims 1-5 or 9 or a composition according to any one of Claims 10-13.