GB2076817A - Dihalovinyl-substituted Cyclopropane Carboxylates - Google Patents

Abstract

Process for the preparation of a compound of the general formula <IMAGE> in which each Hal independently represents a fluorine, chlorine or bromine atom and R represents an alkyl group containing 1 to 10 carbon atoms characterised in that a trihalo- compound of formula <IMAGE> wherein R has the same meaning as given above, at least one Hal is a bromine atom and each of the other two Hal's individually represent a fluorine, chlorine or bromine atom, and Q is hydrogen or the group -COOM in which M in an alkali metal atom, is reacted with a phosphorus trihalide in which the halide is bromide or chloride. The compounds of formula I are useful intermediates in the manufacture of pyrethroid insecticide.

Description

SPECIFICATION Process for the Preparation of 2,Z-Dihalovinyl- substituted Cyclopropanecarboxylates This invention relates to a process for the preparation of 2,2-dihalovinyl-substituted cyclopropanecarboxylates. These compounds are of economic importance because they represent the acid portion of the insecticidally-active pyrethroid esters, e.g. permethrin, cypermethrin and decamethrin all of which are derived from 3phenoxybenzyl alcohol and alpha-cyano-3 phenoxybenzyl alcohol.

The general formula of the acid portion of these pyrethroid esters is as follows:-

where Hal represents a halogen atom. These acids exist in the cis and transforms and, generally speaking, esters based on the cis-acids are more insecticidally-active than esters based on the corresponding trans-acids. The high level of activity of these pyrethroid esters has provided a stimulus to the search for new and economic routes to the acid of formula (A).

U. S. Patent Specification No. 4,018,838 discloses a process for the preparation of dihalosubstituted straight or branched chain alkenes by the reductive dehydrohalogenation of alpha-haloalcohols using zinc and acetic acid.

U. S. Patent Specification No. 4166063, discloses the reaction of a cis-hydroxy acid of the general formula

in which X1, X2 and X3 when identical are selected from the group consisting of chlorine and bromine and when at least two are different are selected from the group consisting of fluorine, chlorine and bromine, with a dehydrating agent, produces a lactone of the general formula

which can be isolated and converted using a reducing agent, such as zinc and acetic acid, manganese, or a zinc-copper couple, into the corresponding cis dihalovinylcyclopropane carboxylic acid. This two step reaction can of course only be used to prepare a cis compound from a cis starting material, since the intermediate lactone cannot exist in trans configuration.

The Applicants have now found that this conversion can be carried out using a single step process without the need to use zinc and acetic acid. Moreover, this single step process is applicable to the preparation of both cis and trans compounds.

The invention provides a process for the preparation of a compound of the general formula

in which each Hal independentiy represents a fluorine, chlorine or bromine atom, and R represents an alkyl group containing 1 to 10 atoms characterised in that a trihalo-compound of formula

wherein R has the same meaning as given above, at least one Hal is a bromine atom and each of the other two Hal's individually represent a fluorine, chlorine or bromine atom, and 0 is hydrogen or the group --COOM in which M is an alkali metal atom, is reacted with a phosphorus trihalide in which the halide is bromide or chloride.

The Hal substituents are preferably all bromine atoms or a combination of bromine and chlorine atoms.

The R substituent is preferably an alkyl group containing 1 to 4 carbon atoms for example methyl, ethyl, isopropyl or tertiary butyl, alkyl groups containing 1 to 3 carbon atoms being more preferred.

When the 0 substituent is a --COOM group, the alkali metal atom is preferably sodium or potassium.

The compounds of the general formulae I and li exist in the form of optical and geometric isomers, and generally, the configuration present in the starting material II is retained in the product I after the process of the invention has been carried out.

Thus a starting material in which the halosubstituted group and the alkoxy carbonyl group are cis or trans to each other may be converted into the compound of formula I with corresponding geometry. Mixtures of isomers can of course be used. Similarly, the use of an optically-active starting material can lead to an optically-active product.

The process according to the invention is suitably carried out in the presence of an inert aprotic solvent, for example an amide such as dimethylformamide or dimethylecetamide; a hydrocarbon such as toluene, cyclohexane or pentane; a ketone such as acetone; an ether such as tetrachydrofuran; sulpholane; N,Ndimethylpyrrolidone; or dimethylsulphoxide.

Dimethyl formamide is the preferred solvent.

Mixtures of solvents are often suitable.

The process is suitably carried out at a temperature in the range of 0 to 2000 C, temperatures in the range of 400 to 1 600 being preferred.

The molar ratios of the reactants are not critical but the ratio of trihalo compound II to phosphorus trihalide is suitably in the range 1:10 to 1 :1, preferably in the range 1:2 to 1:1.1.

The starting material of the general formula Il in which Q represents a hydrogen atom may be prepared by any suitable method. Conveniently, a keto acid of general formula

in which Hal and R have the meanings given above, is reduced with a reducing agent capable of selectively reducing the keto group. This reduction may for example be carried out using sodium borohydride in an aqueous medium at room temperature or below. The cis or trans relationship of the groups on the cyclpropane ring is maintained on reduction.

The starting material of the general formula Il in which Q represents the groupCOOM can be prepared by the process disclosed in our copending application European patent application 80200240.

The following examples further illustrate the invention. The term "selectivity" used in the examples has the following meaning. The selectivity to a certain component expressed in a percentage, is defined as a/bx 100, wherein "a" is the amount of the starting compound converted into that certain compound and "b" is the amount converted starting compound.

Example I Preparation of Ethyl trans-2'-(2,2 dibromovinyl)-3',3'-dimethyl-cyclopropane- carboxylate An NMR tube was charged with a solution of 40 mg (0.095 mmol) ethyl trans-2'-(2,2,2tribromo- 1 -hydroxy-ethyl)-3',3 '-dim ethyl cyclopropane carboxylate and 14.5 mg (0.105 mmol) phosphourustrichloride in 0.5 ml N,Ndimethylformamide (DMF). After heating for 35 minutes at 500C the reaction mixture was diluted with 1 ml water and extracted with 0.5 ml CDCI3.

The CDCl3 layer was washed with three times with 1 ml water, dried over MgS04 and analysed by NMR and GLC. Conversion 100%, selectivity 93% ethyl trans-2 '-(2,2-dibromovinyl)-3',3'- dimethyl-cyclopropane-carboxylate.

Example II Preparation of Methyl cis-2'-(2,2 dibromovinyl )-3'-3'-dimethyl-cyclopropane Ca rboxyl ate The above compound was prepared in a onepot procedure in which at first sodium 2,2,2 tribromo- 1 -(3',3'-dimethyl-2'-methoxy-carbonylcyclopropyl)ethyl carbonate was prepared by adding 1.5 g cis-methylcaronaldate (9.6 mmol) during five minutes at 50C to a suspension of 4 g sodium tribromoacetate (12.5 mmol) in 1 5 ml DMF (DMF was dried over mol. sieves). And after stirring for 50 min at 50C 1.1 ml PCl3 (12.5 mmol) was added during 2 min while cooling (exothermic reaction temp. 1 50C). Subsequently the reaction mixture was heated during 30 min at 800C and quenched in 75 ml water after cooling to room temperature.Afterwards the organic phase was extracted with pentane (3x 1 5 ml) and the collected pentane extracts were combined and washed with water (2x20 ml) and a saturated NaHC03 solution (2x20 ml), dried over anhydrous MgS04, filtered and the solvent was removed under reduced pressure leaving a yellow oil (3.2 g) of which the content of methyl cis-2' (2,2-dibromovinyl)-3',3'-dimethylcyclopropane- carboxylate was more than 90%. The conversion of the starting methyl ester was more than 95% with a selectivity to the dibromovinyl compound of more than 95%.

Example Ill Preparation of Methyl cis-2'-(2-bromo-2 chloro-vinyl)-3',3'-dimethyl-cyclopropane- carboxylate 106 mg PCl3 (0.77 mmol) was added to a solution of 160 mg (0.44 mmol) methyl cis-2 (2,2-dibromo-2-chloro- 1 -hydroxyethyl)-3,3dimethyl-cyclopropane-carboxylate in 0.5 ml DMF and the mixture was heated during 30 min at 600C. Working up of the product afforded methyl cis-2'-(2-bromo-2-chlorovinyl)-3',3'-dimethyl- cyclopropane-carboxylate. Conversion and selectivity were more than 95%.

Example IV Preparation of Ethyl trans-2'-(2,2 dibromovinyl )3',3')-dimethyl-cycloprnpane- caboxylate 0.12 mmol (50 mg) ethyl trans 2'-(2,2,2 tribromo- 1 -hydroxy-ethyl)-3 ',3 '-dimethyl- cyclopropane-carboxylate and 0.13 mmol (35 mg) phosphorus tribromide were heated during 30 minutes at 500C in 0.5 ml DMF. Ethyl trans 2'-(2,2 dibromovinyl)-3',3'-dimethyl- cyclopropane-carboxylate was obtained in more than 95% yield. Conversion 100%, selectivity more than 95%.

Comparative Example A comparative experiment was carried out by the preparation of ethyl trans-2'-(2,2 dibromovinyl)-3',3'-dimethyl-cyclopropane- carboxylate by reacting the trihalo compound with zinc/acetic acid.

0.35 mmol (23 mg) Zn was added to a stirred solution of 0.24 mmol (100 mg) ethyl trans-2' (2,2,2-tribromo- 1 -hydroxyethyl)-3',3'-dimethyl- cyclopropane-carboxylate in 230 í acetic acid at 500C. After 40 minutes the clear solution was diluted with 10 ml water and extracted with pentane (3x5 ml). The collected pentane extracts were washed with water (3x5 ml), dried over Mg SO4, filtered and the solvent was removed under reduced pressure leaving 52 mg of an oil.

Conversion 85%, selectivity to dibromovinylester 21%(NMR and GLC analyses), the rest being over-reduced compounds.

Conversion and selectivity of the above reaction using zinc/acetic acid are much lower than those obtained from the reactions according to the present invention.

Claims (9)

Claims

1. Process for the preparation of a compound of the general formula:

in which each Hal independently represents a fluorine, chlorine or bromine atom and R represents an alkyl group containing 1 to 10 carbon atoms characterised in that a trihalocompound of formula

wherein R has the same meanings as given above, at least one Hal is a bromine atom and each of the other two Hal's individually represent a fluorine, chlorine or bromine atom, and Q is hydrogen or the groupCOOM in which M is an alkali metal atom, is reacted with a phosphours trihalide in which the halide is bromide or chloride.

2. A process according to claim 1 characterised in that the Hal substituents are all bromine atoms or a combination of bromine and chlorine atoms.

3. A process according to claim 1 or 2 characterised in that the alkali metal atom represented by M is sodium or potassium.

4. A process according to claim 1,2 or 3 characterised in that the R substituent is an alkyl group containing 1 to 3 carbon atoms.

5. A process as claimed in any one of the preceding claims, characterised in that it is carried out at a temperature in the range 400C to 1609C.

6. A process as claimed in any one of the preceding claims, characterised in that the reaction of the trihalo compound II with the phosphorus halide is carried out in the presence of a polar, aprotic solvent.

7. A process as claimed in any one of the preceding claims, characterised in that the molar ratio of the trihalo compound (Il) to the phosphorus trihalide is in the range 1:2 to 1:1.1.

8. A process as claimed in claim 1, substantially as hereinbefore described with reference to the Examples.

9. 2,2-Dihaiovinyl compounds of the general formula I whenever prepared by a process as claimed in any one of the preceding claims.