GB1572183A

GB1572183A - Cyclopropane carboxylic acid ester synthesis and intermediates therefor

Info

Publication number: GB1572183A
Application number: GB36688/75A
Authority: GB
Original assignee: Wellcome Foundation Ltd
Current assignee: Wellcome Foundation Ltd
Priority date: 1975-09-05
Filing date: 1975-09-05
Publication date: 1980-07-23
Also published as: IT1068211B; IL50407A; IL50407A0; SE7609748L; CH627432A5; NL7609841A; DE2639777A1; JPS60243042A; JPS6220176B2; CH636073A5; BR7605865A

Abstract

Compounds of the formula VI in which the radicals have the meanings given in Claim 1 are prepared by eliminating the acid R<1>OH from a compound of the formula V in which R<1> denotes a radical derived from a strong acid R<1>OH. The compounds of the formula V are intermediates for the preparation of insecticides. <IMAGE>

Description

(54) CYCLOPROPANE CARBOXYLIC ACID ESTER SYNTHESIS AND INTERMEDIATES THEREFOR (71) We, THE WELLCOME FOUNDATION LIMITED, of 183-193 Euston Road, London N.W.I., a company incorporated in England, do hereby declare the invention tor 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 a novel method of making known vinylcyclopropane carboxylate esters, the esters so prepared, and to certain novel intermediates useful in the method and their synthesis.

British Patent Specification No. 1 413491 discloses compounds of the general formula (A):

wherein, inter alia, R2 and R3 are each halo and R is alkyl, hydrogen (or a salt or acid halide derivative of the acid), as intermediates for the synthesis of insecticidal esters of formula (I) wherein B is a cyclic residue as further defined and illustrated hereinafter, and R2 and R3 are each halo. In this specification halo means chloro or bromo. These insecticidal esters have shown promising activity against a great variety of arthroped pests.

One method of synthesis involves the reaction of 1,1-dihalo-4-methyl-1,3- pentadiene with an alkyl diazoacetate. This synthesis is however hazardous in view of the toxicity and explosive character of the diazoacetates.

Another method of synthesis involves a Wittig synthesis according to the following equation:

2 /ph R2 2 + gC-Halogen 2 d R3 fl2 \C:P/PPhh OCll-(H-CII-CO2R + \/ ) Compound of general formula (A) C C113 C3 wherein R, R2 and R3 have the same meaning as in formula (A), but unfortunately the synthesis leads to the formation of an undesirable impurity and ring opening (J. Chem. Soc. 2470, 1974 and Supplement Publication No. SUP 2113 at page 9).

It has now been found that the esters of formula (I) can be conveniently made by the synthetic route outlined below in Scheme A.

SCHEME A

This route involves the formation of compounds of formulae (II) to (VII) wherein each of R2 and R3 is chloro or bromo and X is nitrile, carboxyl, carbonamide optionally substituted by one or two lower alkyl groups, carbonylhalide or an ester group. Suitable ester groups are of the formula COOM wherein M is C16 alkyl -such as ethyl, aralkyl such as benzyl, and cyclic groups of formula (B) defined hereinbelow.

In the method of the present invention it has been surprising found that the dihalo compounds (III) can be readily formed by halogenation of the acetyl compounds (II) without contamination with the monohalo compounds or formation of the corresponding trihalo -compounds. Moreover, it was found possible to convert the secondary alcohols (IV) to the desired vinyl compounds (Vl) by first forming an ester (V), wherein R'O is a radical derived from a strong organic acid R1OH, and eliminating in step (d) the acid R'OH which may then be reused to form further ester (V), without opening the cyclopropane ring.

Chlorination of the acetyl compounds (II) is preferably carried out using sulphuryl chloride. The reaction may be carried out at low temperatures, e.g. from O" to 500C, though reflux temperatures may be used. Desirably the sulphuryl chloride should be present in a molar excess, e.g. from 2 to 4 or even 10 times the molar equivalent of an acetyl compound (II). Preferably the reaction is carried out in the absence of a solvent, though one may be used, e.g. carbon tetrachloride, if desired.

Chlorination may also be effected by using molecular chlorine in the presence of a catalyst, such as peroxide (e.g. benzoyl peroxide) or light, particularly ultraviolet light. Alternatively a catalyst is not required if the chlorination is effected using molecular chlorine in carbontetrachloride, this reaction being conveniently carried~out at room temperature.

Bromination of the acetyl compounds (II) may be achieved using liquid bromine in the presence of an inert solvent such as ether; the reaction proceeds readily at room temperature.

The reduction (b) of the dihalo compounds (III) to the hydroxy compounds (IV) may be effected by any method known for the reduction of ketones to secondary alcohols. Such methods include the use of sodium with ethanol; sodium or aluminium amalgam and water; catalytic hydrogenation with for example a nickel catalyst such as Raney nickel; and the Ponndorf method using an alcohol and an aluminium alkoxide, such as aluminium isopropoxide and isopropanol.

Preferably reduction is achieved using a hydride, for example sodium borohydride, preferably in the presence of a solvent such as an alkanol, an ether such as dioxan, or an aqueous solution thereof.

In step (c), an alcohol (IV) may be converted to its ester (V) by reaction with the acid R1.OH or a reactive derivative thereof such as the acid chloride or bromide or anhydride. The acid R1.OH is a strong acid, preferably a strong organic acid and is preferably an alkyl-, aralkyl- or aryl- sulphonic acid for example ptoluenesulphonic acid, trifluoromethanesulphonic acid, methanesulphonic acid, pbromobenzenesulphonic acid, or a haloalkanoic acid such as trichloroacetic acid or trifluoroacetic acid. Conveniently, a solvent is used such as pyridine, and the reaction is readily effected at room temperature. The olefine (VI) may then be produced from the ester (V) by elimination of the acid R'OH in the presence of a base. In order to minimise the competitive substitution reaction, the conditions should be chosen which favour elinination by using a strong base. Examples of such reactants include an alkali metal alkoxide, such as sodium methoxide or ethoxide or potassium tertiary butoxide, in the corresponding alkanol; an alkali metal hydroxide such as sodium hydroxide in an alkanol; and potassium tertiary butoxide in a non-polar solvent such as benzene or toluene or in a halogenated aliphatic hydrocarbon solvent such as carbon tetrachloride, dichloromethane or dichloroethane; the reaction may be effected at room temperature or with heating up to the reflux temperature of the reaction mixture.

When employing the synthetic route outlined in Scheme A it is of course possible to vary, if desired, the value of the radical X from one group to another within the definition given above; for example it maybe convenient to effect step (a) using an alkyl ester, but thereafter to convert the compound of formula (III) to the desired ester of an alcohol B.OH before proceeding with the synthesis.

Similarly it is essential that for any particular step, the radical X should be compatible with the reactants which are used.

If in the compound of formula (VI) the variable X is an ester of the desired alcohol B.OH, wherein B is as defined hereinbelow, then the resulting olefin is the required insecticidal ester of formula (I). Alternatively, the olefin (VI) may be converted to the appropriate ester by conventional techniques such as transesterification or by hydrolysis (where necessary) to the acid (VII) followed by esterification.

For example, compounds of formula (VI) wherein X is other than carboxyl may be converted into the corresponding carboxylic acid of formula (VII) by standard techniques such as acid or alkaline hydrolysis. Conveniently, using suitable conditions for the elimination reaction (vide supra) and an excess of base appropriate, a compound of formula (V) may be converted directly to the carboxylic acid (VII) without isolation of the intermediate (VI).

The insecticidal esters of formula (I) may be prepared by esterification of the alcohol BQ or a reactive derivative thereof with the acid (VII) or a reactive derivative thereof of formula (VIIl):

wherein R2 and R3 are each halo, and Q and Q' are functional groups or atoms which react together to form an ester linkage and B has the value defined hereinbelow.

Conveniently the acid (VII), its acid anhydride with chloroformic acid, or acid chloride (formula (VIII): Q' is chloro) are reacted with an alcohol BOH; or a halide BHal is reacted with a salt of the acid (VII), for example the sodium, silver or triethylammonium salt; or an acid (VII) or a reactive derivative therof such as an alkali metal salt is reacted with a quaternary ammonium salt BA+Hal- wherein A is an alkyl amine and Hal is a halide. Alternatively an ester of formula (VI) (wherein X is a group COOM) is subjected to transesterification with an alcohol BOH in the presence of a basic catalyst.

The starting acetyl compounds (II) may be made by any known method, such as that described in U.S. Patent No. 3,397,223, for example by the reaction shown in Scheme (B) below wherein X has the same meaning as in formula (II).

SCHEME B

In this scheme, the compounds of formula (II) are prepared by the reaction of mesityl oxide (XIII) with a dimethylsulphuranylidene compound (XII). The latter reactant (XII) may itself be prepared from a corresponding substituted dimethyl sulphonium salt (XI) obtained from compound (X) wherein 'Hal' is a halogen such as bromo, and dimethyl sulphide.

The sulphonium compound (XI) is preferably made by reaction of dimethyl sulphide with compound (X) in a polar or non-polar solvent at room temperature.

The resulting sulphonium product (XI) may then be dehydrohalogenated by a base such as alkali metal hydroxide, alkoxide or hydride in an alkanol. Preferably an aqueous alkali metal carbonate solution and chloroform are used to minimise the ;)$:r; decomposition of the ylide (XII).

Those Those acetyl compounds (II) which are esters of an alcohol BOH are S ~ niently prepared by known techniques from other corresponding acetyl S rpounds. For example by transesterification of the alkyl ester or hydrolysis and esterification analagous to the conversion of an olefin of formula (VI) to a compound of formula (I).

In the desired insecticidal esters of formula (l) the cyclic residue B is selected from the class of the formula BOH wherein B is:

wherein Z represents 0, S, CH2 or CO, Y represents hydrogen or an alkyl, alkenyl or alkynyl group or an aryl or furyl group which is unsubstituted or substituted in the ring by one or more alkyl, alkenyl or alkoxy groups or halogen atoms; R7 and R8, which may be the same or different, each represent hydrogen or an alkyl or alkenyl group; Rg represents hydrogen or a methyl group; R'O and R11, which may be the same or different, each represent hydrogen or an alkyl group; R12 represents an organic radical having carbon-carbon unsaturation in a position a to the CH2 group to which R12 is attached;

indicates an aromatic ring or a dihydro or tetrahydro analogue thereof; X1, X2, X3 and X4, which may be the same or different, each represent hydrogen, chlorine or a methyl group; and represents -CH2 or -0- or -S- or -CO-; D represents H, CN or --CrCH; Z' and Z2, which may be the same or different, each represent chlorine or a inethyl group; and n is 0, I or 2.

Highly active examples of such insecticidal esters of formula (I) include those derived from 5-benzyl-3-furylmethyl alcohol (in formula (XIV): Z-Y is 5-benzyl, D = D = R7 = R8 is hydrogen) and m-phenoxybenzyl alcohol (in formula (XVII): Z3 is oxygen, D is hydrogen, n is 0). Other specific esters within the scope of the above classes are described in detail in British Patent No. 1 413 491.

Synthesis of the acetyl compounds (II) by the reactions outlined in Scheme B specifically provides the desired pure trans geometrical isomers, and the subsequent reaction sequence to the vinyl esters (VI) retains the trans configuration. Nevertheless, if desired, any trans compound of formula (II) to (VII) may be converted into its cis isomer or a cis/trans mixture for the purpose of producing the cis or cis/trans insecticidal compounds of formula (I).

Conveniently a cis/trans mixture may be produced by converting a compound of formulae (II), (III), (V) or (VI) to its acid chloride, and heating the acid chloride above 100 C, for example to 1 100C to 150 C. Heating the acid chloride of the acid (VII) leads to an equilibrium mixture of 2025: 8075 cis/trans ratio. Alternatively the conversion to cis/trans mixtures may effected by ultra-violet irradiation, and such mixtures may be separated 6y any known method including distillation of an ester (R is alkyl) or fractional crystallisation of the corresponding acids (R is hydrogen).

The intermediates of formulae (II) to (VII), as well as the insecticidal esters of formula (I) may exhibit optical as well as geometrical isomerism.

The formation of the cyclopropane ring at an early stage in the route to (VI) and (VII), permits resolution, if required, of the optical isomers of the racemate starting acetyl compounds (II) to obtain the more active insecticidal (+) isomers of compounds (I) via the (+) isomers of compounds (II) to (V).

The racemates of any of these compounds may be resolved into the (+) and (-) isomers to produce the corresponding (+) or (- insecticidal esters, or the racemates may themselves be used to produce the racemic insecticidal esters of formula (I).

The racemates of compounds (II) to (VI) may be resolved by known methods, preferably by optical resolution of the corresponding (+) acid with an optically active base, for example an alkaloid such as quinine, or a-phenylethylamine, or threo- 1 -p-nitrophenyl-2-(N,N-dimethylamino)propane- 1,3-diol.

The following Examples illustrate the invention.

Example 1.

A: Carboethoxymethyl dimethylsulphonium bromide A solution of ethyl bromoacetate (530g, 3.17M) and dimethyl sulphide (228g, 3.67M) in acetone (1.0 1) was stirred at room temperature for three days. Filtration of the mixture yielded the sulphonium bromide as a white crystalline solid m.p.

78--9"C.

B: Ethyl (dimethylsulphuranylidene) acetate A solution of sulphonium bromide (85.7g, 0.37M) in chloroform (280ml) was vigorously stirred at 5--10"C and treated in one portion with a mixture of saturated potassium carbonate solution (212ml) and l2.5N sodium hydroxide solution (29.5ml). The reaction mixture was warmed to 15--200CX and was held there for 15 minutes. After removal of the salt by filtration, the filtrate was separated and the upper chloroform layer dried for 2 hours over anhydrous potassium carbonate.

Removal of the solvent in vacuo at 250C and Imm mercury pressure gave the ylide as a pale yellow oil.

C: (i) Trans Ethyl 3-acetyl-2,2-dimethylcyclopropane-l-carboxylate A solution of the ylide (49.3g, 0.33M) and mesityl oxide (146g, 1.49M) in dry benzene (750ml) was refluxed for 18 hours. Removal of the solvent and excess reagent by distillation gave a residue. This liquid was fractionally distilled and the cut boiling at 450C and 0.1 mum mercury pressure collected to yield the desired cyclopropane as a colourless liquid.

Example 2.

(+) Trans Ethyl 3-dichloroacetyl-2,2-dimethylcyclopropane-1-carboxylate Sulphuryl chloride (59.4g, 0.44M) was added dropwise to ethyl3-acetyl-2,2dimethylcyclopropane- I-carboxylate (20.4g, 0.11M) with ice cooling. The solution was stirred at room temperture for 16 hours. Excess reagent was removed under vacuum and the residue dissolved in ether (50ml). The ether was washed with water, dried over anhydrous sodium sulphate and evaporated in vacuo to give a pale yellow liquid bp 85 C/0.05mm/mercury.

Example 3.

(+) Trans Ethyl 3-(,-dichloro-a-hydroxyethyl)-2,2-dimethylcyclopropane 1 carboxylate Solid sodium borohydride (2.4g, 0.063M) was added portionwise to a cooled solution of (~) Trans ethyl 3-dichloroacetyl-2,2-dimethylcyclopropane- 1 carboxylate (16.0g, 0.063M) in methanol (160ml). The reaction was stirred at room temperature for 3 hours. Most of the methanol was removed in vacuo and the residue poured into ice/water (150ml). This was extracted with ether (3 x the ether extracts combined, dried over anhydrous sodium sulphate and evaporated in vacuo to yield the hydroxy compound as a pale yellow liquid b.p.

1 lObC/0.07mm mercury.

Example 4.

(+) Trans Ethyl 3-,-dichloro-a-hydroxyethyl)-2,2-dimethylcyclopropane 1 - carboxylate Aluminium isopropoxide (0.97g, 0.005M) and (+) trans ethyl 3-dichloro acetyl-2,2-dimethylcyclopropane-l-carboxylate (1.0g, 0.004M) were refluxed in isopropanol (6.0ml) for 16 hours. On cooling, the mixture was poured into 2N hydrochloric acid (50ml) and then extracted with ether (3 x 30ml) The combined organic layers were extracted with water (2 x 50ml), dried and evaporated in vacuo to yield a colourless oil. This product was identical (n.m.r. and l.r. spectra and g.l.c.) to the title product obtained from the sodium borohydride reduction described above in Example 3.

Example 5.

Trans Ethyl 3-(A,-dichloro-a-tosyloxyethyl)-2,2-dimethylcyclopropane- I - carboxylate A solution of (+) trans ethyl - 3-(p"B-dichloro-a-hydroxyethyl)-2,2- dimethylcyclopropane-l-carboxylate (28.0g, 0.1 IM) in pyridine (168ml) was added dropwise to a solution of tosyl chloride (44.2g, 0.23M) in pyridine (224m1) maintained at 40"C. After the addition the mixture was stored for 3 days at 40C.

The majority of the pyridine was removed under vacuum at 400C and the residue was poured into ice/water (200 ml). After the acidification with concentrated hydrochloric acid, this mixture was extracted with ether (3 x 100ml), the ether layers combined, dried and evaporated to a pale yellow oil, which crystallised on standing. The tosylate was recrystallised from cyclohexane, m.p. 71 CC.

Example 6.

(+) Trans Ethyl 3-(A,-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylate (+) Trans ethyl 3-(A,-dichloro--tosyloxyethyl)-2,2-dimethylcyclopropane-1- carboxylate (0.5g, 0.0012M) and N sodium hydroxide solution (2.5ml) in ethanol (2.5ml) were refluxed for 1 hour. On cooling the mixture was poured into water (20ml), acidified with concentrated hydrochloric acid and extracted with ether (3 x 10ml). The combined organic phases were washed with water (2 x 15my), dried over anhydrous sodium sulphate and evaporated in vacuo. to yield a colourless oil.

This oil was identical (n.m.r. and i.r. spectra and g.l.c.) with an authentic sample of the title ester.

Example 7.

(+) Trans 3-(,-dichlorovinyl)-2,2-dimethylcyclopropane- -carboxylic acid (+) Trans ethyl 3-(,fi-dichlorvinyl)-2,2-dimethylcyclopropane- 1 -carboxylate (4.2g, 0.018M) and N sodium hydroxide solution (36.0ml) in ethanol (36.0ml) were refluxed for 1 hour. On cooling, the mixture was poured into water (200ml) and acidified with concentrated hydrochloric acid. This was extracted with ether (3 x lOOml), the ether layers combined, washed with water (2 x l00ml), dried over the anhydrous sodium sulphate and evaporated in vacuo. An off-white solid was produced and recrystallisation was achieved from cyclohexane to yield the title acid, m.p. 94--95QC.

Example 8.

(+) Trans 3-( , dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid A mixture of (+) trans ethyl 3 -(P,p-dichloro-a-tosyloxyethyl)-2,2- dimethylcyclopropane-l-carboxylate (lO.Og, 0.024M) in ethanol (lOOml) and N sodium hydroxide solution (lOOml) were refluxed for I hour. Excess alcohol was removed under vacuum and the residue acidified with concentrated hydrochloric acid, and extracted with ether (3 x60ml). The combined ether layers were extracted with saturated brine (2 x lOOml), dried over anhydrous sodium sulphate and evaporated in vacuo to yield the acid as a cream solid. Recrystallisation was achieved from cyclohexane m.p. 93--5"C (Lit. 95--6").

Example 9.

(I) Trans m-Phenoxybenzyl 3-(p,p-dichlorovinyl)-2,2-dimethylcyclop 1 - carboxylate (+) Trans 3-(A,-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (1.0g, 0.0048M), m-phenoxybenzyl alcohol (I.Og, 0.0050M) and para4oluene sulphonic acid (0.01g) in toluene (lOOml) were refluxed with a Dean and Stark takeoff for 36 hours. On cooling, the solution was extracted with 5% aqueous sodium bicarbonate (2 x 50ml), then water (2 x 50ml), dried over anhydrous sodium sulphate and evaporated in vacuo. The residue was passed down an acid washed alumina column using petroleum ether (b.p. 800-lOO0C) as eluant. On evaporation of the solvent, this yielded a colourless oil which crystallised on standing. The product was identical (n.m.r., i.r. and u.v. spectra, t.l.c. and g.l.c.) to an authentic sample of the title ester.

Example 10.

A: (t, Trans Ethyl 3-(A,-dichloro-a-brosyloxyethyl)-2,2-dimethylcyclopropane-1- carboxylate A solution of (+) trans ethyl 3-( , -dichloro-α-hydroxyethyl)-2,2- dimethylcyclopropane-l-carboxylate (5.0 g, 0.020 m) in pyridine (30 ml) was added dropwise to a solution of brosyl chloride (10.18 g, 0.040 m) in pyridine (30 ml) maintained at 400 C. After the addition the mixture was stirred at room temperature for 3 days and then poured into water (200 ml), acidified with concentrated hydrochloric acid, extracted with ether (3 x 80 ml), dried over anhydrous magnesium sulphate and evaporated in vacuo to give a white solid. This was recrystallised from cyclohexane m.p. 83 C.

B: By a similar reaction wherein the brosyl chloride is replaced by mesyl chloride was prepared (+) trans ethyl 3-(A,-dichloro-a-mesyloxyethyl)-2,2-dimethylcyclo- propane-l -carboxylate, which is a pale yellow liquid.

a(CDCl3) 1.12-1.39(9H,m), 1.62-2.15(2H,m), 3.18(3H,s), 4.18(2H,q,J 7Hz), 4.70(1H,d of d,J 3 & 9 Hz), 6.03(lH,d,J 3Hz).

Example 11.

(+) Trans Ethyl 3-( , -dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylate A: A mixture of the brosylate product of Example 10A(1.3 g, 0.0027 m) in ethanol (5.4 ml) and N sodium hydroxide solution (5.4 ml) was refluxed for 1 hour.

After cooling the reaction mixture was poured into water (100 ml) and acidified with concentrated hydrochloric acid. This was extracted with ether (3 x 50 ml), Example 12.

(+) Trans Ethyl 3-(,B,-dichloro-a-trifluoroacetoxyethyl)-2,2-dimethylcyclo- propane- I -carboxylate (±) Trans ethyl 3-(p,p-dichloro-cu-hydroxyethyi)-2,2-dim 1 - carboxylate (1.0 g, 0.004 m) was treated with trifluoroacetic anhydride (5.0 g, 0.024 m) and the mixture stirred at room temperature for 16 hours, in a moisture free atmosphere. Excess reagent was removed in vacuo, leaving the trifluoroacetate as a pale yellow liquid. This was stored in the absence of moisture and used without further purification.

ACDCI3) 1.081.41(9Hz,m), 1 .57-2.07(2H,m), 4.18(2H,1,J7Hz), 5.06(1H,d of d,J5 & 9 Hz). 5.92(1H,W5Hz).

Example 13.

(+) Trans Ethyl 3-(,B,-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylate The trifluoroacetate product of Example 12 (2.0 g, 0.0057 m) in dry benzene (15 ml) was treated with potassium tertiary butoxide (0.96 g, 0.0086 m) and the mixture stirred at room temperature for 20 hours. This was evaporated in vacuo and the residue extracted with 40/60 petroleum ether. After filtration the petrol was evaporated in vacuo and the residue separated by g.l.c.

Example 14.

Trans 3-Acetyl-2,2-dimethylcyelopropane- 1 -earboxylic acid Ethyl 3-acetyl-2,2-dimethylcyclopropane-l-carboxylate (36.0 g, 0.2 m) and N potassium hydroxide (391 ml) in ethanol (391 ml) was refluxed for two hours.

Excess alcohol was removed in vacuo and the resulting solution acidified with concentrated hydrochloric acid (approx. 40 ml). This precipitated a solid which was extracted with ether (3 x 200 ml), the ether dried over anhydrous MgSO4 and evaporated in vacuo to give a cream solid m.p. 111"C.

Example 15.

(+) Trans 3-Acetyl-2,2-dimethylcyelopropane-l-earboxmide Thionyl chloride (45.7 g, 0.40 m) was added dropwise to a solution of 3-acetyl 2,2-dimethylcyclopropane-1-carboxylic acid (30.0 g, 0.20 m) in benzene (300 ml) and the mixture refluxed for two hours. Excess solvent and reagent were removed in vacuo and the residue dissolved in dimethoxyethane (320 ml). This solution was added to dimethoxyethane (1600 ml) which had been saturated with ammonia gas and the mixture stood at room temperature for 16 hours. After removal of some inorganic salts by filtration, the~filtrate was evaporated in vacuo to give a white solid which was identified as the required amide.

Example 16.

+) Trans 3-Acetyl- 1 -cyano-2,2-diemthylcyclopropane Phosphorus oxychloride (202.4 g, 1.32 m) was added dropwise to a solution of 3-acetyl-2,2-dimethylcyclopropane- 1 -carboxamide. (34.6 g, 0.22 m) in benzene (140 ml) and the resultant mixture refluxed for 3 hours. Excess reagents were removed in vacuo and the residue dissolved in ether (100 ml). The ether was washed with water (3 x60 ml), dried over anhydrous magnesium sulphate and evaporated in vacuo to give a dark oil b.p. 72-50C/l.0 mm.

Example 17.

(+) Trans B enzyl 3-Acetyl-2,2-dimethylcyclopropane- 1 -carboxylate Thionyl chloride (25.5 g, 0.21 m) was added dropwise to a solution of 3-acetyl2,2-dimethylcyclopropane-1-carboxylic acid (16.7 g, 0.11 m) in dry benzene (250 ml) and then refluxed for 2 hours. This mixture was evaporated in vacuo, the residue taken up in benzene (100 ml) and re-evaporated. This residue was dissolved in benzene (150 ml) and benzyl alcohol (13.1 g, 0.12 m) added. After cooling the mixture in ice, pyridine (11.3 g, 0.12 m) was added dropwise and the mixture stirred at room temperature for 16 hours. This organic phase was extracted with 2N sodium hydroxide solution (2 x 80 ml), water (2 x 80 ml), N

Example 18.

(+) Trans B enzyl 3-Dichloroacetyl-2,2-dimethylcyclopropane- I -carboxylate Sulphuryl chloride (39.5 g, 0.29 m) was added dropwise to benzyl 3-acetyl-2,2 dimethylcyclopropane-l-carboxylate (18.0 g, 0.07 m) with ice cooling. This solution was stirred at room temperature for 16 hours. Excess reagent was removed under vacuum and the residue dissolved in ether (100 ml). The ether was washed with water (2 x 50 ml), dried over anhydrous magnesium sulphate and evaporated in vacuo to give a viscous oil.

a(CDCl3) 1.38(3H,s), 1.58(3H,s), 2.74(1H,d,J6Hz), 3.17(1H,d,J6Hz), 5.41(2H,s), 6.11(1H,s), 7.69(5H,s).

Example 19.

(+) Trans B enzyl 3-(p,-Dichloro--hydroxyethyl)-2,2-dimethylcyclopropane-1- carboxylate Solid sodium borohydride (2.56 g, 0.068 m) was added portion-wise to a cooled solution of the product of Example 18 (21.3 g, 0.068 m) in methanol (200 ml). The reaction was stirred for 3 hours at room temperature and then most of the methnaol was removed under vacuum. The residue was poured into ice/water (200 ml) and extracted with ether (3 x 100 ml). The combined organic layers were dried over anhydrous magnesium sulphate and evaporated in vacuo to yield a yellow oil.

Purification was effected by running down a grade III alumina column (100 g) using 40/60 petroleum ether as eluent to remove a fast running by-product. Then further elution with toluene gave the required dichloro alcohol.

8(CDCI3) 1.32(6H,s), 1.52-I .91 (2Hsn), 2.62(l H, broad s, exchangeable with D2O), 3.51-3.79(Iff,m) 5.79(1H,d, J4Hz), 7.44(SH,s).

v max (film 3457, 1730, 1165, 1117, 791, 733, 698 cm-l Example 20.

(+) Trans B enzyl 3-(A"B-Dichloro-cr-tosyloxyethyl)-2,2-dimethylcyclopropane-1- carboxylate A solution of the product of Example 19 (5.0 g, 0.016 m) in pyridine (30 ml) was added dropwise to a solution of tosyl chloride (6.0 g, 0.032 m) in pyridine (30 ml) and the mixture allowed to stand for 3 days at room temperature. Most of the pyridine was removed under vacuum and the residue was poured into ice/water (200 ml). This was acidified with concentrated hydrochloric acid and extracted with ether (3 x 100 ml). The combined ether layers were dried over anhydrous magnesium sulphate and evaporated in vacuo to give a thick oil. This was triturated with 40/60 petroleum ether to yield the tosylate as an off-white solid.

Recrystallisation was achieved from 60/80 petroleum ether mp. 98"C.

a(CDCl3) 1.21(3H,s), 1.24(3H,s), 1.76--2.22(2H,m), 2.52(3H,s), 4.72(1H,d of d, J 3 & 9Hz), 5.22(2H.s), 5.99(1H.dJ3Hz), 7.26-7.95(9H,m).

v max (mull) 1726, IZfl, 1117, 920, 840, cm-' Example 21.

(+) Trans B enzyl 3-(ss,-Dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylate Potassium tertiary butoxide (0.74 g, 0.0066 m) was added to the product of Example 18 (2.0 g, 0.0044 m) in dry benzene (100 ml) and the mixture refluxed for 16 hours. On cooling, the reaction was poured into ice/water (200 ml) and acidified with concentrated hydrochloric acid. The organic layer was separated and the aqueous layer extracted with ether (2 x 100 ml). The combined organic layers were dried over anhydrous magnesium sulphate and evaporated in vacuo to yield a brown oil. This was purified by running down a grade III alumina column (6 g) using 60/80 petroleum ether as eluent and this yielded the desired compound as a colourless oil.

This product was identical (n.m.r. and i.r. spectra, t.l.c. and g.l.c.) with an authentic sample.

a(DCl3) 1.18(3-H,s), 1.34(3H,s), 1.67(1H,d,J6Hz), 2.29(1H,d of d, J 6 & 9Hz), 5.18(2H,s), 5.67(1H,d,J9Hz), 7.42(5H,s).

v max (film) 1731, 1225, 1166, 1117, 882, 698 cam~' Example 22.

Meta Phenoxybenzyl (Dimethylsulphuranylidene) Acetate A solution of carbo-(meta-phenoxybenzoxy)methyl dimethylsulphonium bromide (50.0 g, 0.13 m) in chloroform (103 ml) was vigorously stirred at 5--100C and treated, in one portion, with a mixture of saturated potassium carbonate solution (78 ml) and 12.5 N sodium hydroxide solution (10.3 ml). The reaction mixture was warmed to 15--200C and was held there for 15 minutes. After removal of the salt by filtration, the filtrate was separated and the upper chloroform layer dried for 2 hours over anhydrous potassium carbonate. Removal of the solvent in vacuo at 250C and I mm pressure gave the ylide as a pale yellow oil.

Example 23.

(+) Trans meta-Phenoxybenzyl 3-Acetyl-2,2-dimethyleyclopropane- 1 -carboxylate a) A solution of the product of Example 22 (34.6 g, 0.11 m) and mesityl oxide (44.7 g, 0.46 m) in ethanol (330 ml) was refluxed for 16 hours. Removal of the solvent and excess reagent in vacuo gave a residue of 37.5 g. This was purified by running down a grade III alumina column (120 g) using 60/80 petroleum ether containing 10% toluene as eluent and this yielded the desired compound as a pale yellow oil.

b) A solution of (+) Trans 3-acetyl-2,2-dimethylcyclopropane-1-carboxylic acid (33.3 g, 0.21 m) in dry benzene (500 ml) was treated with thionyl chloride (50.8 g, 0.42 m) and refluxed for 2 hours. This was evaporated in vacuo to remove all excess reagents and the residue was dissolved in dry benzene (300 ml). Meta phenoxybenzyl alcohol (38.3 g, 0.21 m) was added followed by dropwise addition of pyridine (16.8 g, 0.21 m) to the cooled solution. The reaction was stirred at room temperature for 16 hours. After filtration, the solution was extracted with 2N sodium hydroxide solution (2 x 100 ml), water (2 x 100 ml), N hydrochloric acid (2 x 100 ml), water (2 x 100 ml) and saturated brine (I x 100 ml), then dried over anhydrous magnesium sulphate and finally evaporated in vacuo to yield the ester.

This product was identical (i.r. and n.m.r. spectra, t.l.c. and g.l.c.) to that prepared via the sulphur ylide above.

Example 24.

(j) Trans meta Phenoxybenzyl 3-Dichloroacetyl-2,2-dimethylcyclopropane- 1- carboxylate a) Chlorine gas (2.1 g, 0.03 m) was dissolved in ice cooled carbon tetrachloride (50 ml) and to this solution was added m-phenoxybenzyl 3-aeetyl-2,2-dimethylcyclo- propane-l-carboxylate (1.3 g, 0.004 m). The flask was stoppered and stood at room temperature for 16 hours. Removal of the solvent in vacuo left a pale yellow oil.

This material was purified by chromatography on a grade III alumina column (8 g) using 40/60 petroleum ether as eluent and the slowest running compound was collected. Spectroscopic identification of this compound showed it to be the desired compound.

CDCl3) 1.29(3H,s), 1.48(3II,s), 2.59(lH,d, J 5Hz), 3.02(1H,d J 5Hz), 4.73(2H,s), 5.22(1H,s), 5.22 (1 H,s) 6.96-7.61 (9H,m).

b) A solution of 3-dichloroacetyl-2,2-dimethyleyclopropane-1-carboxylic acid (1.0 g, 0.004 m) in dry benzene (25 ml) was treated with thionyl chloride (1.2 g, 0.008 m) and refluxed for 2 hours. This was evaporated in vacuo to remove allexee reagents and the residue dissolved in dry benzene (25 ml.) Meta phenoxybenzyl alcohol (0.8 g, 0.004 m) was added, the mixture cooled in ice and pyridine (0.4 g, 0.005 m) added dropwise. The reaction was stirred at room temperature for 16 hours. After filtration, the solution was extracted with 2N sodium hydroxide solution (2 x 20 ml), water (2 x 20 ml), N hydrochloric acid (2 x 20 ml), water (2 x 20 ml) and saturated brine (1 x 20 ml), then dried over anhydrous magnesium sulphate and finally evaporated in vacuo to give the ester. This product, a pale yellow oil, was identical (i.r. and n.m.r. spectra, t.l.c. and g.l.c.) to the material prepared above.

Example 25.

(+) Trans meta-Phenoxybenzyl 3-(A,-dichloro-a-hydroxy ethyl)-2,2-dimethylcyclo propane-l-carboxylate Sodium borohydride (3.17 g, 0.084 m) was added portionwise to a cooled solution of the product of Example 24 (34.0 g, 0.084 m) in methanol (300 ml). The reaction was stirred for 3 hours at room temperature and then most of the methanol was removed in vacuo, before pouring the residue into ice/water (300 ml). This was extracted with ether (3 x 150 ml), the combined ether layers dried over anhydrous magnesium sulphate and the ether finally evaporated to yield a viscous oil.

Purification was effected by running down a grade III alumina column (150 g) using 60/80 petroleum ether as eluent to remove a fast running by-product. Then further elution with 60/80 petroleum ether containing 10% toluene gave the required dichloro alcohol.

CDCl ) 1.39(6H,s), 1.69-1.94(2H,m), 2.63(1H,s exchangeable with D2O), 3.543.83(1H,m), 5.20(2H,s), 5.81(1H,d,J 5Hz), 6.99-7.56(9H,m).

Vmix (film) 3462, 1732, 1589, 1490, 1258, 1216, 1165, 692 cm~t Example 26.

(+) Trans meta-Phenoxybenzyl 3 -dichloro--tosyloxyethyl)-2,2-dimethylcyclo- propane- 1 -carboxylate A solution of the product of Example 25 (12.5 g, 0.03 m) in pyridine (50 ml) was added dropwise to solution of tosyl chloride (12.1 g, 0.063 m) in pyridine (50 ml) and the mixture allowed to stand for 3 days at room temperature. Most of the pyridine was removed in vacuo and the residue poured into ice/water (300 ml). This was acidified with concentrated hydrochloric acid and extracted with ether (3 x 150 ml). The combined ether layers were dried over anhydrous magnesium sulphate and evaporated in vacuo to give a viscous oil. This oil was purified by elution through a grade III alumina column (50 g) using 40/60 petroleum ether.

(CDC13) 0.94(3H,s), 1.08(3H,s), 1.38-I .9o(2H,m), 2.23(3H,s), 4.49(1H,d of d, J3 & 9Hz), 4.96(2H,s), 5.92(1H,d, J 3Hz), 6.75-7.81(13H,m).

vm.x (film) 1732, 1590, 1491, 1258, 1216, 1178, 692 cam~'.

Example 27.

(+) Trans meta-Phenoxybenzyl 3-(ss,-dichlorovinyl)-2,2-dimethylcyclopropane-1- carboxylate Potassium tertiary butoxide (0.45 g, 0.004 m) was added to the product of Example 26 (1.0 g, 0.002 m) in dry benzene (20 ml) and the mixture refluxed for 16 hours. On cooling the reaction was poured into ice/water (100 ml) and acidified with concentrated hydrochloric acid. The organic layer was separated and the aqueous layer extracted with ether (2 x 50 ml). The combined organic layers were dried over anhydrous magnesium sulphate and evaporated in vacuo to give a yellow oil. Purification was effected by chromatography on a grade III alumina column (3 g) eluting with 40/60 petroleum ether to produce a white solid. m.p. 45"C. This product was identical (i.r. and n.m.r. spectra and t.l.c. and g.l.c.) to authentic material.

Example 28.

(+) Trans Ethyl 3-dibromoaeetyl-2,2-dimethylcyclopropane- 1 -earboxylate Bromine (26.0 g, 0.160 m) was added dropwise to ethyl 3-acetyl-2,2 dimethylcyclopropane-l-carboxylate (12.0 g, 0.065 m) in ether (600 ml). The solution was extracted with 10% sodium bicarbonate solution (3 x 200 ml) and water (2 x 200 ml), dried over anhydrous magnesium sulphate and evaporated in vacuo to yield a pale yellow liquid. No further purification was attempted with this compound.

Example 29.

(±) Trans Ethyl 3-(p,p-dibromo-a-hydroxyethyl)-2,2-dimet 1 - carboxylate Solid sodium borohydride (2.38 g, 0.063 m) was added portionwise to a cooled solution of the dibromo ketone product of Example 28 (21.6 g, 0.063 m) in methanol (300 ml). The reaction was stirred at room temperature for 3 hours. Most of the methanol was removed in vacuo and the residue poured into ice/water (200 ml). This was extracted with ether (3 x 100 ml), the ether combined, dried over raydrous magnesium sulphate and evaporated in vacuo to yield the hydroxy compound as a pale yellow oil b.p. 1300C./0.1 mm.

Example 30.

(+) Trans Ethyl 3-(ss,-Dibromo-a-tosyloxyethyl)-2,2-dimethylcyclopropane- 1 carboxylate A solution of the product of Example 29 (I 1.0 g, 0.032 m) in pyridine (63 ml) was added dropwise to a solution of tosyl chloride 12.7 g, 0.067 m) in pyridine (92 ml) and the mixture allowed to stand for 3 days at room temperature. The majority of the pyridine was removed under vacuum and the residue poured into ice/water (100 ml). After acidification, with concentrated hydrochloric acid, the mixture was extracted with ether (3 x 50 ml), the ether layers were combined, washed with water (3 x 50 ml), then brine (1 x 100 ml), dried over anhydrous magnesium sulphate and evaporated in vacuo to yield a pale yellow oil (15.1 g). this oil was taken up in petroleum ether (600 ml) and on standing the tosylate crystallised out as white prisms. Recrystallisation was achieved from 40/60 petroleum ether m.p.

84"C.

Example 31.

(+) Trans 3-(A,-Dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid A mixture of the product of Example 30 (3.7 g, 0.0074 m) in ethanol (30 ml) and N sodium hydroxide solution (29.6 ml) were refluxed for 3 hours. Excess alcohol was removed under vacuum and the residue was acidified with concentrated hydrochloric acid. On standing a pale yellow precipitate was deposited which was filtered off, washed with water and dried. Recrystallisation was achieved from 40/60 petroleum ether m.p. 1254 C.

Example 32. RESOLUTION Trans 3-Acetyl-2,2-dimethyleyclopropane- 1 -carboxylie acid (+) Trans 3-Acetyl-2,2-dimethyleyclopropane-l-carboxylic acid (4.0 g, 0.026 m) was dissolved in a mixture of diisopropyl ether (170 ml) and methanol (30 ml).

This solution was warmed to 600C and (+) cg-methylbenzylamine (3.1 g, 0.026 m) added. The mixture was refluxed for 30 minutes and then cooled. The resulting crystals were removed by filtration and reerystallised twice from a mixture of diisopropyl ether and methanol (80:10). This gave a solid (2.3 g) with constant specific rotation of +10.12". Hydrolysis of this salt with 2 N hydrochloric acid (30 ml), extraction into ether (2 x 20 ml), drying of the ether layers over anhydrous magnesium sulphate and final evaporation in vacuo gave the (+) acid (1.1 g, 54% yield). Reerystallisation was achieved from ethanol. N.m.r. analysis of the product using Eu(hfc)3 showed the optical purity to be 62% (+) and 38% (-).

Example 33.

(+) Trans 3-Dichloroacetyl-2,2-dimethyleyelopropane- I -earboxylic acid Sulphuryl chloride (69.1 g, 0.51 m) was added dropwise to (+) Trans 3-acetyl 2,2-dimethylcyclopropane-l-carboxylic acid (10.0 g, 0.064 m) in ether (100 ml) with ice cooling. The solution was stirred at room temperature for 16 hours. Excess reagent and solvent were removed in vacuo and the residue dissolved in ether 100 ml). The ether was washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo to give a pale yellow liquid b.p. 130"C/0.7 mm.

Example 34.

Isomerisation of (+) Trans 3-Aeetyl-2,2-dimethyl-cyclopropane-1-carboxylic Acid (+) Trans 3-Acetyl-2,2-dimethylcyclopropane-l-carboxylie acid (2.0 g, 0.013 m) and thionyl chloride (3.28 g, 0.026 m) in toluene (10 ml) were refluxed for one hour. Excess reagent and solvent were removed in vacuo and the residual acid chloride heated at 1440C for seven hours. On cooling, the mixture was neutralised with 2N sodium hydroxide solution then acidified with concentrated hydrochloric acid. This was extracted with ether (3 x 30 ml), the ether dried over anhydrous magnesium sulphate and evaporated in vacuo to yield a white solid (1.9 g, yield 95%). H.P.L.C. on an o.d.s. column showed presence of cis isomer (approximate ratio 70/30 trans/cis) and n.m.r. of product was indentical to the trans isomer.

WHAT WE CLAIM IS: 1. A method for preparing a vinyl compound of formula (VI):

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

Claims

**WARNING** start of CLMS field may overlap end of DESC **. Example 30. (+) Trans Ethyl 3-(ss,-Dibromo-a-tosyloxyethyl)-2,2-dimethylcyclopropane- 1 carboxylate A solution of the product of Example 29 (I 1.0 g, 0.032 m) in pyridine (63 ml) was added dropwise to a solution of tosyl chloride 12.7 g, 0.067 m) in pyridine (92 ml) and the mixture allowed to stand for 3 days at room temperature. The majority of the pyridine was removed under vacuum and the residue poured into ice/water (100 ml). After acidification, with concentrated hydrochloric acid, the mixture was extracted with ether (3 x 50 ml), the ether layers were combined, washed with water (3 x 50 ml), then brine (1 x 100 ml), dried over anhydrous magnesium sulphate and evaporated in vacuo to yield a pale yellow oil (15.1 g). this oil was taken up in petroleum ether (600 ml) and on standing the tosylate crystallised out as white prisms. Recrystallisation was achieved from 40/60 petroleum ether m.p. 84"C. Example 31. (+) Trans 3-(A,-Dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid A mixture of the product of Example 30 (3.7 g, 0.0074 m) in ethanol (30 ml) and N sodium hydroxide solution (29.6 ml) were refluxed for 3 hours. Excess alcohol was removed under vacuum and the residue was acidified with concentrated hydrochloric acid. On standing a pale yellow precipitate was deposited which was filtered off, washed with water and dried. Recrystallisation was achieved from 40/60 petroleum ether m.p. 1254 C. Example 32. RESOLUTION Trans 3-Acetyl-2,2-dimethyleyclopropane- 1 -carboxylie acid (+) Trans 3-Acetyl-2,2-dimethyleyclopropane-l-carboxylic acid (4.0 g, 0.026 m) was dissolved in a mixture of diisopropyl ether (170 ml) and methanol (30 ml). This solution was warmed to 600C and (+) cg-methylbenzylamine (3.1 g, 0.026 m) added. The mixture was refluxed for 30 minutes and then cooled. The resulting crystals were removed by filtration and reerystallised twice from a mixture of diisopropyl ether and methanol (80:10). This gave a solid (2.3 g) with constant specific rotation of +10.12". Hydrolysis of this salt with 2 N hydrochloric acid (30 ml), extraction into ether (2 x 20 ml), drying of the ether layers over anhydrous magnesium sulphate and final evaporation in vacuo gave the (+) acid (1.1 g, 54% yield). Reerystallisation was achieved from ethanol. N.m.r. analysis of the product using Eu(hfc)3 showed the optical purity to be 62% (+) and 38% (-). Example 33. (+) Trans 3-Dichloroacetyl-2,2-dimethyleyelopropane- I -earboxylic acid Sulphuryl chloride (69.1 g, 0.51 m) was added dropwise to (+) Trans 3-acetyl 2,2-dimethylcyclopropane-l-carboxylic acid (10.0 g, 0.064 m) in ether (100 ml) with ice cooling. The solution was stirred at room temperature for 16 hours. Excess reagent and solvent were removed in vacuo and the residue dissolved in ether 100 ml). The ether was washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo to give a pale yellow liquid b.p. 130"C/0.7 mm. Example 34. Isomerisation of (+) Trans 3-Aeetyl-2,2-dimethyl-cyclopropane-1-carboxylic Acid (+) Trans 3-Acetyl-2,2-dimethylcyclopropane-l-carboxylie acid (2.0 g, 0.013 m) and thionyl chloride (3.28 g, 0.026 m) in toluene (10 ml) were refluxed for one hour. Excess reagent and solvent were removed in vacuo and the residual acid chloride heated at 1440C for seven hours. On cooling, the mixture was neutralised with 2N sodium hydroxide solution then acidified with concentrated hydrochloric acid. This was extracted with ether (3 x 30 ml), the ether dried over anhydrous magnesium sulphate and evaporated in vacuo to yield a white solid (1.9 g, yield 95%). H.P.L.C. on an o.d.s. column showed presence of cis isomer (approximate ratio 70/30 trans/cis) and n.m.r. of product was indentical to the trans isomer. WHAT WE CLAIM IS:

1. A method for preparing a vinyl compound of formula (VI):

wherein each of R2 and R3 is chloro or bromo, and X is nitrile, carboxyl, carbonamide optionally substituted by one or two C16 alkyl groups, carbonyl halide, or a group -COOM wherein M is C,, alkyl, aralkyl, aryl or a group B selected from:

wherein Z represents 0, S, CH2 or CO, Y represents hydrogen or an alkyl, alkenyl or alkynyl group or an aryl or furyl group which is unsubstituted or substituted in the ring by one or more alkyl, alkenyl or alkoxy groups or halogen atoms; R7 and R8, which may be the same or different, each represent hydrogen or an alkyl or alkenyl group; R9 represents hydrogen or a methyl group; R10 and R11, which may be the same or different, each represent hydrogen or an alkyl group; R12 represents an organic radical having carbon-carbon unsaturation in a position a to the CH2 group to which R12 is attached;

.indicates an aromatic ring or a dihydro or tetrahydro analogue thereof; X1, X2, X3 and X4, which may be the same or different, each represent hydrogen, chlorine or a methyl group; and Z3 represents -CH2 or -0- or -S- or -CO-; D represents H, CN or -C=-CH; Z1 and Z2, which may be the same or different, each represent chlorine or a methyl group; and n is 0, 1 or 2; characterised in that one eliminates an acid R1.OH from a compound of formula (V):

wherein R2, R3 and X are as defined in formula (VI), and R1 is a radical derived from the strong organic acid of formula R1.OH, by treatment with a strong base.

2. A method as claimed in claim 1 characterised in that the acid R'.OH is an alkylsulphonic acid, arylsulphonic acid, aralkylsulphonic acid or haloaikanoic acid.

3. A method as claimed in any preceding claim characterised in that the acid R'.OH is selected from p-toluenesulphonic acid, trifluoromethane sulphonic acid, methanesulphonic acid, p-bromobenzenesulphonic acid, trichloroacetic acid and trifluoroacetic acid.

4. A method as claimed in any preceding claim characterised in that the acid R1.OH is p-toluenesulphonic acid.

5. A method as claimed in any preceding claim characterised in that the base is an alkali metal alkoxide in an alkanol, or an alkali hydroxide in an alkanol.

6. A method as claimed in any preceding claim characterised in that the base is potassium tertiary butoxide in a non-polar solvent, an alkanol, or a halogenated aliphatic hydrocarbon,

7. A method as claimed in claim 6 characterised in that the solvent is selected from benzene, toluene, carbontetrachloride, dichloromethane and dichloroethane.

8. A method as claimed in any preceding claim characterised in that the reaction is effected at a temperature up to the reflux temperature of the reaction mixture.

9. A method as claimed in any preceding claim characterised in that the compound of formula (V) is prepared by reacting the acid of formula R1.OH as defined in claim 1, or a reactive derivative thereof, with an alcohol of formula (IV):

wherein R2 and R3 are as defined in formula (VI) and X is as defined in claim 1.

10. A method as claimed in claim 9 characterised in that the reactive derivative of R1.OH is selected from the acid chloride, acid bromide and acid anhydride.

11. A method as claimed in either claim 9 or 10 characterised in that the alcohol of formula (IV) is prepared by reduction with an appropriate selective reducing agent of a ketone of formula (III):

wherein R2 and R3 are as defined in formula (VI) and X is a group as defined in claim 1.

12. A method as claimed in claim 11 characterised in that the reduction is effected using sodium in ethanol, sodium or aluminium amalgam in water, catalytic hydrogenation, an alcohol and an aluminium alkoxide, or a hydride.

13. A method as claimed in either of claims 11 or 12 characterised in that the ketone of formula (III) is prepared by halogenation of a compound of formula (II):

wherein X is as defined in claim 1.

14. A method as claimed in claim 13 characterised in that the compound of formula (II) is chlorinated using sulphurylchloride or molecular chlorine.

15. A method as claimed in claim 13 characterised in that the compound of formula (II) is brominated with liquid bromine.

16. A method for preparing a compound of formula (VI) as claimed in any preceding claim characterised in that, when X is other than a group --COOB, said compound of formula (VI) is converted, if required, to an esterifiable derivative of formula (VIII):

'rh.rein R2 and R3 are as defined in formula (VI), and said compound of formula * > II) is reacted with a compound BQ wherein B is as defined in claim I, and Q and Q1 are functional groups or atoms which react together to form an ester linkage; to provide the desired insecticidal ester of formula (VI) wherein X is a group -COO B as defined in claim 1.

17. A method as claimed in any preceding claim characterised in that, when in the compound of formula (V) X is other than carboxyl or a group -COOB, said compound is reacted with base to provide an acid of formula (VII):

wherein R2 and R3 are as defined in formula (V), and, optionally via a compound of formula (VIII), said compound of formula (VII) is esterified to provide the desired insecticidal ester of formula (VI) as defined in claim 18.

18. A method as claimed in any of claims 1 to 16 characterised in that X is carboxyl, alkyloxycarbonyl or aralkyloxycarbonyl.

19. A method as claimed in any of claims 1 to 16, or 18 characterised in that X is ethoxycarbonyl or benzyloxyearbonyl.

20. A method as claimed in any of claims 1 to 15 characterised in that X is a groupCOOB as defined in claim 1.

21. A method as claimed in any of claims I to 15 or 20 eharacterised in that B is m-phenoxybenzyl.

22. A method as claimed in any preceding claim characterised in that a compound of formula (II), (III), (IV), (V), (VI), (VII) or (VIII) has the trans configuration.

23. A method as claimed in any preceding claim for preparing a compound of formula (VI), (VII) or (VIII) substantially as hereinbefore described with particular reference to the Examples.

24. A method as claimed in any of claims 1 to 17, and 20 to 23 characterised in that the compound of formula (VI) is trans (+) m-phenoxybenzyl 3-(2,2 dichlorovinyl)-2,2-dimethyleyelopropane- 1 -earboxylate.

25. A compound of formula (VI), (VII) or (VIII), as defined in claims 1, 17 and 16 respectively, when prepared by the process claimed in any preceding claim.

26. A compound of formula (VI) wherein X is a groupCOOB as defined in claim 1 when prepared by the process as claimed in claim 16.

27. A compound of formula (V):

wherein each of R2 and R3 is chloro or bromo, and X is nitrile, carboxyl, carbonamide optionally substituted by one or two C16 alkyl groups, carbonyl halide, or a groupCOOM wherein M is C16 alkyl, aralkyl, aryl or a group B selected from:

wherein Z represents 0, S, CH2 or CO, Y represents hydrogen or an alkyl, alkenyl or alkynyl group or an aryl or furyl group which is unsubstituted or substituted in the ring by one or more alkyl, alkenyl or alkoxy groups or halogen atoms; R7 and RB, which may be the same or different, each represent hydrogen or an alkyl or alkenyl group; R9 represents hydrogen or a methyl group; R10 and R1', which may be the same or different, each represent hydrogen or an alkyl group; R12 represents an organic radical having carbon-carbon unsaturation in a position cr to the CH2 group to which R12 is attached;

indicates an aromatic ring or a dihydro or tetrahydro analogue thereof; X1, X2, X3 and X4, which may be trite same or different, each represent hydrogen, chlorine or a methyl group; and Z3 represents -CH2- or -0- or -S- or -CO-; D represents H, CN or -C=-CH; Z1 and Z2, which may be the same or different, each represent chlorine or a methyl group; and n is O, 1 or 2; and R' is a radical derived from a strong organic acid of formula R'.OH.

28. A compound as claimed in claim 27 wherein Xis a group COOB as defined in claim 27.

29. A compound as claimed in claim 27 wherein X nitrile, carboxyl, carbonyl halide, carbonamide optionally substituted by one or two C1 alkyl groups, or a group COOM wherein M is C18 alkyl, aryl or aralkyl.

30. A compound as claimed in claim 27 wherein X is ethoxycarbonyl or benzyloxycarbonyl.

31. A compound as claimed in claim 28 wherein B is m-phenoxybenzyl.

32. A compound as claimed in any of claims 27 to 31 having the trans configuration.

33. A compound as claimed in any of claims 27 to 32 wherein the acid R'.OH is an alkyl sulphonic acid, arylsulphonic acid, aralkylsulphonic acid or haloalkanoic acid.

34. A compound as claimed in any of claims 27 to 33 wherein R1 is a radical derived from an acid R1.OH selected from p-toluenesulphonic acid, trifluoromethanesulphonic acid, methanesulphonic acid, p- bromobenzenesulphonic acid, trichloroacetic acid, and trifluoroacetic acid.

35. A compound selected from Trans ethyl 3-( , -dichloro-α-tosyloxyethyl)-2,2-dimethylcyclopropane-1- carboxylate; (+) Trans ethyl 3- -dichloro--brosyloxyethyl)-2,2-dimethylcyclopropane- 1 carboxylate; (+) Trans ethyl 3-(A,-dichloro-a-trifluoroacetoxyethyl)-2,2-dimethylcyclo- propane-1-carboxylate; (+) Trans benzyl 3-(,B,-dichloro--tosyloxyethyl)-2,2-dimethylcyclopropane- 1 - carboxylate ; (+) Trans m-phenoxybenzyl 3-(,B"B-dichloro--tosyloxyethyl)-2,2-dimethylcyclo- propane- 1 -carboxylate; and (+) Trans ethyl 3-(#,#-dibromo--tosyloxyethyl)-2,2-dimethylcyclopropane- 1 carboxylate