CA1118796A - Intermediates in the preparation of cyclopropane- carboxylate esters and process for their manufacture - Google Patents

Abstract

ABSTRACT
Compounds of the general formula:-

Description

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"~ovel intermediates in the preparation of oyclopropane-carboxylate esters and process for their manufacture"

~he invention relates to compounds which are u~eful intermediates in the preparation of cyclopropanecarboxylate ester3. ~he invention also relates to a proces~ for the preparation of these intermediate~.
~he cyclopropanecarboxylate estsrs are insecticidally-active compounds ~nown as "pyrethroids~ and as they combine exceptionally good insecticidal properties with a very low mammalian toxicity, they are of considerabl~ interest to the agrochemical industry and much effort has been expended in finding economic routes to them and to their principal intermediates.
The general formula of one class of the~e pyrethroid compounds may be represented as follows:-C~=CX

CH~ ~ COOR (I) where each a~terisk denotes an asymmetric carbon atom; eachX is 8 halogen atom~ and R is a member of a group of radicals known to impart insecticidal activity to the molecule, e.g. 3-phenoxybenzyl or alPha-cyano-3-phenoxy-bsnzyl. It i3 ~nown that the stereoisomeric form of the acid portion of the es~er of formula I should be in the (lR,cis) form for maximu~ insecticidal activity, i.e. the absolute configuration at carbon atom 1 is R and the two hydrogen atom~ on carbon atoms 1 and 3 are in a cis relationship. ~his nomenclature i9 known as the Elliott nomenclature and i8 defined in M. Elliott, A.W. Farnham, N.F. James, P.~. ~eedham and D.~. Pullman, ~ature, 1974, ~879~;

It follows, therefore, that if these stereoisomeric esters of for-mula I are to be prepared, either a stereospecific chemical route is required or the desired stereoisomer must be obtained from a racemic form by physical sepa-ration techniques. The latter are expensive and laborious and not readily em-ployed on an industrial scale. The Applicant has found a stereospecific route which uses as starting material the naturally-occurring substance (+)-3-carene ~hose formula is as follows:- CH3 ,, / ~II) CH3 `H

This compound is an inexpensive readily-available natural terpene and the present application relates to intermediates in a route to the (lR,cis~-acid portion of the pyrethroid ester of formula I starting from (-~)-3-carene.

The present invention provides compounds of the general formula:-H ~CH=CHal2 / \ ~ O-C113 (III) CH / \ CH -CH

wherein each Hal represents a chlorine or bromine atom.
Preferably the compounds of formula III are in the same stereoiso-meric form as that of the cyclopropane ring of (+)-3-carene.
A preferred compound of the general formula III is 2-[2-(2,2-dichloro-vinyl)-3,3-dimethylcyclopropyl]ethanal dimethyl acetal.

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Particularly preferred are those compounds having the same stereoisomeric form aa that of the cyclopropa~e ring of (~)-3-carena, e.g. the compound prepare~ in the Example~.
The compounds and their preferred stereoisomeric form according to the invention may be prepared by proce~ses known per se, for example, according to the method~
disclosed in ~ Patent Specification 1,413,491 which discloses the preparation of dihalovinylcyclopropyl compounds by reacting 3-formyl-2,2-dimethylcyclopropane-carboxylate with a dihalomethylenephosphorane (which can beprepared by reaction of a trior~anophosphine, normally triphenylphosphine, with a carbon tetrahalide).
~ he compounds and their isomers according to the invention ar~ preferably prepared by a process charscterised in that (a) a tri(dialkylamino)phosphine or an alkyl ester of an orthophosphorous acid bi3(dialkylamide) i~ raacted with a tetrahalomethane or a trihalomethane and (b) the product resulting from the first step i8 reacted with an aldehyde of the general formula:-~ CH0 X (I~) _0-C~3 H~ 3 both 6teps bsing carried out in the presence of a substan-tially inert solvent. Preferably step (a) is allowed to proceed to sub3tantial completion.
The slkyl groups present in the tri(dialkylamino) phosphine or the alkyl ester of an ortho-phosphorous acid bis(dialkylamide) may be the same or different and linear or branched. The alkyl groups are suitably the 9ame, have preferably less than si~ carbon atoms and more preferably less than three. ~he use of tri(dialkylamino)phosphines i8 L87~

preferred, because they usually affora the compounds of formula III in a higher yield than the alkyl e~ters of ortho-phosphorous scid bis(dialkylamines) (the lattar compounds are obtained by replacin~ one of the dialkyl-amino groups in a tri~dialkylamino)pho3phine by an alkoxygroup). Tri(diethylamino)phosphine and tri(dimethylamino) phosphine are most preferred.
Tri(dialkylamino)phosphines may be prepared by reaction of a dialkylamine ~ith a pho3phorous trihalide, a3 described in "Organic Synthesi3", Coll.Yol. V (1973) 602-603. ~hi3 reaction results in the formation of a solution of the tri(dialkylamino)-phosphine which also contains precipitated dialkylammonium halide. According to a feature of the pre3ent in~ention a tri(dialkylamino)-phosphine may be preparad by reacting a dialkylamine with a pho3phorous trihalide in ~he presence of a substantially-inert sol~ent. The resultin~ reaction mixture can then be washed with water to remoYe unwanted by-products (whether or not after prior separation of the precipitated dialkyl-ammonium halide) and the tri(dialkylamino)phosphine dissol-~ed in the ~ashed solution reacted with the halomethane.
It is not necessary to separate the precipitated di~lkyl-ammonium halide prior to washing, because this salt is water-soluble. The yield of the compound of formula III can be further enhanced by drying the washed liquid, for eYample, over a solid drying agent such as anhydrous 30dium sulphate or snhydrous magnesium sulphate.
Another attractive feature of the process according to the pres~ t invention is that it may be carried out in the pre~ence of an alkane solvent, for example, alkane solvents with a boiling point or boiling range up to 200C.
This also applies to the said reaction batween a dialkyl-amine and a pho~phorous trihalide. Examples of alkane solYents are pentane, hexane, heptane, octane and nonane.
Mixtures of alkanes are ~ery suitable, for example, gasoli-7~

nes having a boiling range from 62C to 82C or from 80C
to 110C. If desired, the proces~ may be carried out in 3ubstantially-inert 301vents other than alkanes, for example, in tetrahydrofuran.
Examples of tetrahalomethanes or trihalomethane3 which are compound3 capable o~ generating a dihalocarbene under the conditions of the proce~s according to ths present invention are carbon tetrahalides, chloroform, bromoform and iodoform. Very good results have been ohtained with carbon tetrahalides. Examples of carbon tetrahalides are carbon tetrachloride, carbon tatrabromide) carbon tetra-iodide,bromotrichloromethane (forming dichlorocarbene) and dibromodifluoromethane (forming difluorocarbene). Very good results haYe been obtained ~ith carbon tetrachloride. These t5 halomethane3 may also act as solvent or co-sol~ent for the process accordin~ to the inYention.
~ oth step~ of the process according to the present invention are preferably carried out at a temperatur~ in the range of from -50C to ~50C, particularly at tempera-tures of fro~ -20C to +35C.
~ ha compounds and proces3 according to the invention are of intersst as part of a multi-step process to pyre-throid insecticides~ e.g. esters based on (lR,cis)-3-(2,2-dichloroYinyl)-2,2-dimethylcyclopropanc carbo~ylic acid.
The following Examples further illustrate the invention. Yields and purities were determined by means of g3s-liquid chromatography and nuclear magnetic resonance (~) spectroscopy. ~he ~ data quoted were recorded at 90 ~z using solution3 of the compound3 in deuterochloro-form; the àbsorptions giYen are relative to a tetramethyl-3ilane standard.

Example I - Pre~aration in two ste~s of C~R~ci~-2-~2 -(2t2-dichlorovin~l)-3,3-dim3thylc~cloprop~1~ethanal dimeth~l acetal Tri(dimethylamino)phosphine (168.3 m~ol) was added over a period of 12 minutes to a stirred solution of CarDon tetrachloride tl67.4 mmol) in pentane (369 ml) kept at 0C under nitrogen in a 1-1 fla3k. Then, the mi~ture in the flask was stirrea for ~0 minutes at 0C.
Thi3 finished the first step.
10At 0C (lR,c-3)-2-(2,2-dimethoxyethyl ~,3-dimethyl-cyclopropanecarbaldehyde (66.4 mmol~ was added dropwi3e to the 3uspension in the flask over a period of nine minutes.
The temperature ~a3 increased to 12C over a period of 15 minutas and stirring was continued at the temperature 15for a further 15 minute3. Thi3 finished the 3econd step.
Then, water (75 ml) was added at 12C and - after removal of the aqueou3 pha3e - the organic phase wa9 wa~hed with two 35-ml portions of wa'sr. Ths washed organic phase was dried over anhydrou3 magns3ium sulphate and the solvent was evaporated from the dried solution to give a residue (17.4 g) containing the title compound (100~6 (lR,cis), purity 88~, yield 91.1~o).
The ~R 3psctrum of the title compound showed the following absorptions:
25~= 1.00 ppm singlet ~ C-C-C~3 c= 1.13 ppm singlet 3 ~ H3C-C-~H~
= 3-33 ppm 3inglet C-(0-CH3)2 ~= 4.33 ppm triplet ~= 5.59 ppm doublet C=CH
multiplets for the two H atoms bound to the ring and for HC-CH2-CH .
ExamPle II - Pre~aration in one ste~ of (lR~cis)-2-[2-(2~2 dichlorov~yl)-~3-dimethylcyclopropyllethanal dimethyl acetal -35~ri(dimethylamino)pho~phine (163.8 mmol) wa~ added with ~tirring at 0C to a solution of (lR,cis)-2-(2,2-dimethoxyethyl)-3,3-dimethylcyclopropanecarbaldehyde (65.5 mmol) and carbon tetrachloride (163.2 mmol) in n-pentane (350 ml) kept under nitrogen in a 1-1 flask. After 15 minutes stirring the mixture wa8 warmed up to 14C and kept at this temperature for 15 minutes. ~hen, water (75 ml) was added at 14C and - after removal of the aqueous pha~e -the organic phsse was washed with two ~5 ml portions of water. ~he washed organic pha3e was dried over anhydrous ma~nesium ~ulphate and the solvent was evaporated from the 10 dried solution to give a residue (15.7 g) containing 32.1 mmol of the title compound (100~,h tlR,cis), purity 51.7%, yield 49%). Comparison with the yield of the title compound obtained in Example I ~hows that the two-step process for the preparation of the title compound ~ives considerably t5 hi~her yields.

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Claims (8)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. Compounds of the general formula:- (III) wherein each Hal is chlorine or bromine atom.

2. Compounds according to claim 1 wherein the compounds are in the same stereoisomeric form as that of the cyclopropane ring of (+)-3-carene.

3. A process for the preparation of compounds of formula III as defined in claim 1 wherein (a) a tri(dialkylamino)phosphine or an alkyl ester of an ortho-phosphorous acid bis(dialkylamide) is reacted with a tetrahalomethane or a trihalomethane and (b) the product resulting from the first step is reacted with an aldehyde of the general formula:

(IV) both steps being carried out in the presence of a substantially inert solvent.

4. A process according to claim 3 wherein the aldehyde of general for-mula IV is in the same stereoisomeric form as the cyclopropane ring of (+)-3--carene.

5. A process according to claim 4 wherein the tri(dialkylamino)phosphine is tri(diethylamino)phosphine or tri(dimethylamino)phosphine.

6. A process according to claim 5 wherein the process is carried out at a temperature in the range -50°C to +50°C.

7. A process according to claim 4, 5 or 6 wherein the sllbstantially-inert solvent is an alkane or tetrahydrfuran

8. A process according to claim 4, 5 or 6 wherein the tetrahalomethane is employed as the substantially-inert solvent.