FR2514349A1 - 3-vinyl-cyclopropane-carboxylate prepn. - by alpha-cyano-3-phenoxy-benzyl 2,2-di:methyl 3-imino-methyl cyclopropane-1-carboxylate(s) hydrolysis and reaction with phosphorane - Google Patents

Abstract

Alpha-cyano-3-phenoxy-nenzyl 2,2-dimethyl-3-Z-iminomethyl cyclopropane-1-carboxylate derivs. of formula (I) and all their stereoisomeric forms (cis or trans, R, S, RS)are new. Z is the residue of a prim. amine Z-NH2 and the acid bond may have a cis or trans, racemic or optically active configuration and the alcoholic bond has R, S or RS configuration. (RS) or (S)-alpha-cyano-3-phenoxybenzyl (IR, cis) or (IR, trans)-2,2-dimethyl-3- (phenyliminomethyl)-cyclopropane-1- carboxylates are specifically claimed.

Description

 The present invention, in the production of which Messrs. MARTEL Jacques, TESSIER Jean and TECHE André, concerns new imines, their preparation process and their application to the preparation of insecticide esters.

The subject of the invention is, in all their reolsomeric forms, the compounds of general formula (I)

 cis or trans R, S or RS in which Z represents the organic residue of a primary amine Z-NH1 and in which the acid copula can be cis or trans, racemic or optically aetive and the alcoholic copula of configuration R, S or RS .

 The substituent Z of the compounds (I) can be chosen from the residues of primary aliphatic amines in particular from the residues of those which positively have at least 6 carbon atoms. The substituent Z can also be chosen from the residues of cyclo aliphatic amines having at least 4 carbon atoms. the substituent Z is chosen preferably from the residues of aromatic primary amines, the phenyl group of which may be optionally substituted in particular by one or more alkyl radicals, one or more alkoxyl radicals, one or more halogen atoms, one or more nitro group , one or more group -503H.

The substituent Z can also be chosen from the residues of aromatic polycyclic amines, optionally substituted
and among the remains of polyeyclanic amines, optionally of the endo-or spirc type.

In the compounds (I) of the invention the substituent Z
is preferably an aniline residue.

Among the compounds of general formula (i) one can ci
ter in particular - (1R, cis) 2,2-dimethyl 3- (phenyllminomethyl) cyclopropane -1- carboxylate of (RS) e cyano 3-phenoxy benzyl - (1R, cis) 2,2-dimethyl 3- (phenyliminomethyl ) cyclopropane -1- (S) cyano 3-phenoxy benzyl carboxylate - (1R, trans) 2,2-dimethyl 3- (phenyliminomethyl) cyclopropane -1- (RS) cyano 3-phenoxy benzylcarboxylate - (1R (trans) 2,2-dimethyl 3- (phenyliminomethyl) cyclo propane-1-carboxylate of (S) cyano 3-phenoxy benzyl.

 The invention also relates to a process for the preparation of the compounds of general formula (I) characterized in that lwon reacts a 2,2-dimethyl 3-formyl cyclopropane -1-carboxylic acid in trans form or in the form of cis lactone a 2,2-dimethyl 3-dihydroxymethyl cyclopropane -1-carboxylic acid (II), with a dehydration reagent chosen from the group consisting of dicyclohexyl carbodiimide and dilsopropyl carbodiimide, and in the presence of pyridine or 4-dimethyl aminopyridine, within a non-polar organic solvent, to obtain 2,2-dimethyl 3formyl cyclopropane -1- (cyclohexylamino) (cyclohexylimino) methyl carboxylate or 2,2-dimethyl 3-formyl cyclopropane -1-carboxylate d '(isopropylamino) (isopropylimino) methyl, whose acid copulas are of trans or cis structure, subjects one of these compounds to the action of alcohol (RS) -cyano 3-phenoxybenzyl (III), within d 'a non-polar solvent ,. to obtain 2,2 dimethyl 3-formyl cyclopropane -1- carboxylate of (RS) oe cyano 3-phenoxy benzyl corresponding (IV), of cis or trans structure, submits, within an organic polar solvent, this racemic ester to the action of a primary amine of formula Z-NH2 in which Z represents the organic residue of a primary amine to obtain 2,2-dimethyl 3- (Z-iminomethyl) cyclopropane -1 (RS) -cyano carboxylate 3-phenoxy benzyl (IA) corresponding, which is subjected, if desired, to the action of a basic agent in a solvent or a mixture of solvents in which the alcohol ester one of the two configurations (R) or (S) is more soluble than its diastereomer, which allows, after epimerization of the benzylic center of the alcoholic copula to obtain, in crystalline form, the only ester corresponding to the configuration favored by insolubility (IB), that is to say either 2,2-dimethyl 3- (Z-iminomethyl) cyclopropane -1- (R) o-cyano 3-phenoxy benzyl carboxylate, so lt 2,2 dimethyl 3- (z-iminomethyl) cyclopropane -1- (S) -cyano 3-phenoxy benzyl carboxylate, the acid coupler of compounds (IA) or (I3) having the same configuration as that of compound II of departure.

 In the process of the invention the non-polar organic solvent in which the aldehyde compound (II) and the dehydrating reagent or the condensation compound and the alcohol (III) are reacted is preferably chosen from the group consisting by eromatic hydrocarbons, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons and cyclohexane.

 In the process of the invention, the primary amine can be chosen from those whose residues have been listed above.

 In a preferred procedure of the process of the invention the primary amine which is reacted with the compound (1V) is aniiine.

 The apolar organic solvent in which the primary amine is reacted and the compound (IV) is chosen. preferably, from the group consisting of aromatic hydrocarbons, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons and cyclohexane.

 In the process of the invention, the basic agent to which the ester (IA) of the configuration alcohol (RS) is subjected is advantageously chosen from the group consisting of ammonia, triethylamine, diethylamine , morpholine, pyrrolidine, piperidine, dilsopropylamine, ephedrine, triethylenediamine, benzylamine, n.

butylamine, sec.butylamine, tetrabutylam monium hydroxide, ion exchange resins of strong basic character comprising quaternary ammoniums or amines, high molecular weight amines and, used in catalytic amount, soda, potash , alkaline alcoholates, alkaline amides, alkaline hydrides, potassium terbutylate and sodium isopropylate.

 The solvent or mixture of solvents in which the configuration alcohol ester 1A (RS) is reacted with the basic agent is preferably chosen from the group consisting of acetonitrile, alkanols and mixtures of alkanols and petroleum ether.

 Without limiting the field of the invention to theoretical considerations, the applicant company believes that the transformation of the ester IA of configuration alcohol (RS) into ester 1a of configuration alcohol (S) or configuration (R) takes place according to the following mechanism. All or part of the form (R) or (S) present in the alcohol ester -IA alcohol (RS) is insolubilized by the action of the solvent or the mixture of insolubilizing solvents used.

The basic agent then racemizes the alcohol ester (R) or residual alcohol (S) to re-form the alcohol ester IA (RS). The mechanism then continues by selective insolubilization of one of the forms (R) or (S), racemization etc ...

dans laquelle X1 et X2, identiques ou différents représentent un radical alcoyle comportant de Ià 4 atomes de carbone, un atome de fluor, de chlore ou de brome, ou représentent ensemble avec l'atone de carbone auquel ils sont liés un homocyle carboné comportant de 3 à 7 atomes de carbone ou un groupement

dans lequel X représente un atome d'oxygène ou de soufre, la copule acide des composés (V) pouvant être de structure cis ou trans, racémique ou opti que ment active et la copule alcoolique étant de configuration (S), ou de configuration (R) caractérisée en ce que l'on soumet un composé de formule (IB) à une hydrolyse à l'aide d'un agent acide, fait réagir au sein d'un solvant (Y), en présence d'une base forte (B) le 2,2-diméthyl 3-formyl cyclopropane -1- carboxylate de (S) -cyano 3-phénoxy benzyle (VI), ou le 2,2diméthyl 3-formyl cyclopropane -1- carboxylate de (R) -cyano 3-phénoxy benzyle tVI) formés, avec un ylure phosphore de formule (VII)

résultant soit de l'action au sein d'un solvant (Y) de la base forte (B) sur le réactif de formule

dans laquelle A - représente un anion dérivé d'un acide minéral, soit
lorsque X1 et X2 représentent un atome d'halogène, de l'action au sein d'un solvant (Y) de la base forte (B) sur la trîphényl phosphine et un haloforme convenable, pour obtenir le composé V désiré dont la copule acide a la même configuration que celle du composé I 9 de départ.A subject of the invention is also the application of the compounds (I) of which the alcoholic copula has a configuration (S) or (R), (compounds 18), in the preparation in all their stereoisomeric forms of the compounds of general formula (V )

in which X1 and X2, identical or different, represent an alkyl radical comprising from 1 to 4 carbon atoms, a fluorine, chlorine or bromine atom, or together represent with the carbon atom to which they are linked a carbon homocyle comprising 3 to 7 carbon atoms or a group

in which X represents an oxygen or sulfur atom, the acid copula of the compounds (V) possibly being of cis or trans structure, racemic or optically active and the alcoholic copula being of configuration (S), or of configuration ( R) characterized in that a compound of formula (IB) is subjected to hydrolysis using an acid agent, reacted in a solvent (Y), in the presence of a strong base ( B) (S) -cyano 3-phenoxy benzyl (VI) 2,2-dimethyl 3-formyl cyclopropane -1- carboxylate, or (R) -cyano 3 2,2-dimethyl 3-formyl cyclopropane -1- carboxylate -phenoxy benzyl tVI) formed, with a phosphorus ylide of formula (VII)

resulting either from the action in a solvent (Y) of the strong base (B) on the reagent of formula

in which A - represents an anion derived from a mineral acid, ie
when X1 and X2 represent a halogen atom, the action within a solvent (Y) of the strong base (B) on triphenyl phosphine and a suitable haloform, to obtain the desired compound V including the acid copula has the same configuration as that of the starting compound I 9.

 In the application according to the invention, the acid agent used in the hydrolysis of the compound Ig is preferably chosen from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid and paratoluene sulfonic acid and the hydrolysis of compound 18 is advantageously carried out in the presence of an organic solvent miscible with water.

 The strong base (B) used is preferably chosen from the group consisting of an alkali hydride, an alkali amide, an alkali alcoholate and butylithium.

 The solvent (Y) is advantageously chosen from the group consisting of dimethylformamide, dimethylsulfoxide, tetrahydrofuran, ethyl ether, monoethyl ether of diethylene glycol and diethyl ether of diethylene glycol.

 To carry out the Wittig reaction which allows the lateral chain to be fixed in position 3 of the ester (V), the ylide VII is prepared by the action of a base on a phosphonium salt or on a mixture of. triphenyl phosphine and haloform, within a polar solvent. Then reacted in the presence of an excess of base, the ylide formed on an aldehyde compound (VI).

 To carry out this de.Wittig reaction, the order of introduction of the reagents can be modified. It is possible, for example, to introduce the base lastly and thus to carry out, simultaneously, the formation of the ylide and its condensation with the aldehyde compound (VI).

 In summary, the process for preparing the compounds (I) of the invention and their application described above, allows a departure of 2,2-dimethyl 3-formyl cyclopropane -1-carboxylic acid in trans form or in the form of lactone cis of a 2,2-dimethyl 3-dihydroxy methyl cyclopropane -1- carboxylic acid (II) and alcohol (RS) -cyano 3-phenoxy benzylic acid (III), to obtain the esters of cyclopropane carboxylic acid (V) of alcohol configuration (R) or (S) with a great insecticidal power and having in position 3 various literal chains.

 As shown in particular in the examples of the experimental part, the synthesis of the compounds (I) according to the invention lends itself well to industrialization. It is indeed possible to carry out several of the reaction stages without intermediate purification or even without intermediate isolation. The reagents and reactions used in the synthesis according to the invention are common and harmless.

The preparation of the compounds (IV) starting from 2,2-dimethyl 3-formyl cyclopropane -1-carboxylic acid in trans form or in the form of cis lactone of a 2,2-dimethyl 3-dihydroxymethyl cyciopropane -1 acid - carboxylic III, has an original character. Indeed an esterification test of the aldehyde compound II and of the alcohol (RS) -cyano 3-phenoxy benzyl leads to a condensation of the alcohol on the aldehyde function and not on the acid function. The passage via compound of the 2,2-dimethyl 3-formyl cyclopropane -1-carboxylate type of (cyclohexylamino) (cyclohexylimino) methyl allows normal esterification for alcohol (RS)
c.cyano 3-phenoxy benzyl to obtain the desired LV-compound.

The preparation of type IV compound for classi
What requires the ozonolysis of a chrysanthemum from (RS) oe-cyano
3-phenoxy benzyl, which has a less industrial character
than the method of the present invention.

The synthesis of the compounds (I) according to the invention leads,
without any risk of failure, to the desired compound (V), whatever
the side channel in position 3 that this ester has (V). In
indeed the epimerization process takes place, in the synthesis
of the invention, on the compound comprising an iminated group
(IA YIB) and gives rise to a satisfactory yield at this stage.

The synthesis according to the invention is therefore free from all hazards
and allows, almost certainly, to obtain a compound (V)
a determined stereochemistry and a determined structure
for the side channel in position 3. This is very valuable for this category of compounds whose biological activity
varies considerably with steric structure.

The subject of the invention is, as new industrial products, useful in particular for the implementation of the process
according to the invention, the compounds whose names follow
- in all their stereoisomeric forms 2,2-dimethyl
3-formyl cyclopropane -1- (cyclohexylamino) carboxylate
(cyclohexylimino) methyl;
- in all their stereoisomeric forms 2,2-dimethyl
3-formyl cyclopropane -1-carboxylate (of isopropylamino) isopropylimino) methyl;
- in all their stereoisomeric forms 2,2-dimethyl 3
(RS) o-cyano 3-phenoxy formyl cyclopropane -1- carboxylate
benzyl;
- in all their stereoisomeric forms 2,2-dimethyl
(S) -cyano 3-phenoxy 3-formyl cyclopropane -1- carboxylate
benzyl.

Example 1: 1R, cis 2,2-dimethyl 3- (2,2-dichlorovinyl) cyclo
(S) -cyano 3-phenoxy benzyl propane -1- carboxylate.

Stage A: 1R îR, cis 2,2-dimethyl 3-formyl cyclopropane -1-
(cyclohexylamino) (cyclohexylimino) methyl carboxylate
2 cm3 are introduced into 400 cm3 of methylene chloride
pyridine, 28.2 g lactone of cis 2,2-dimethyl 3 S acid
(dihydroxy methyl) cyclopropane-1R-carboxylic, add 41.2 g of dicyclohexyl carbodjimide, stir for 1 hour at 200C and obtain a solution of 1R, cis 2,2-dimethyl 3-formyl cyclopropane -1-carboxylate of (cyclohexylamino) (cyclohexylimino) methyl.

Stage 8: 1R, cis 2,2-dimethyl 3-formyl cyclopropane -1 (RS) -cyano 3-phenoxy benzylcarboxylate.

 To the previously obtained solution is added a solution of 28 g of alcohol (RS) -cyano 3-phenoxy benzyl in 150 cm3 of methylene chloride, stirred for 16 hours at 200C, eliminates, by filtration the residual insoluble material, washing the organic phase with water, with a 2N aqueous solution of hydrochloric acid, with water, dried, concentrated to dryness by distillation over reduced pressure, adds ethyl ether to the residue, filters, concentrates to dryness and obtains 59 , 1 g of 7R, cis 2,2-dimethyl 3formyl cyclopropane -1- carb-oxylate of (RS) -cyano 3-phenoxy benzyl crude benzyl, used as it is for the following stage.

Stage C: 1R, cis 2,2-dimethyl 3- (phenylLminomethyl) cyclopropane -1- (RS) -cyano 3-phenoxy benzyl carboxylate.

 59.1 g of the product obtained in Stage 8, 12.5 cm3 of aniline are introduced into 400 cm3 of benzene, concentrated to dryness and 77 g of 1R, cis 2,2-dimethyl 3- (phenylimino methyl) cyclopropane are obtained. 1- crude (RS) -cyano 3-phenoxy benzyl carboxylate used as it is for the following stage.

Stage D: 1R, cis 2,2-dimethyl 3- (phenylimino methyl) cyclopropane -1-carboxylate of (S) O-cyano 3-phenoxy benzyl.

 In 300 cm3 of isopropanol and 5 cm3 of triethylamine are introduced the 77 g of 1R, cis 2,2-dimethyl 3- (phenylimmino methyl) cyclopropane -1- carboxylate of (RS) o-cyano 3-phenoxy benzyl obtained with stage C, primer, agitates for 60 hours at ZOOC, cools at OOC, isolates by spin the crystals formed, dries and obtains 17 g of 1R, cis 2,2-dimethyl 3 (phenylimino methyl) cyclopropane -1- carboxylate of (S ) cyano 3-phenoxy benzyl, F = 1160C.

Stage E: 1R, cis 2,2-dimethyl 3-formyl cyclopropane -i.

(S) oe.cyano 3-phenoxy benzyl carboxylate.

 5 g of 1R, cis 2,2-dimethyl 3- (phenylimino methyl) cyclopropane -1- (S) O-cyano 3-phenoxy benzylcarboxylate, stirred for 4, are introduced into 100 cm3 of 2N aqueous hydrochloric acid solution hours and 30 minutes at 20 C, extracted with methylene chloride, washed with water, concentrated to dryness by distillation under reduced pressure, chromatographs the residue on silica gel, eluting with benzene and obtains 3.8 g of 1R, cis 2,2-dimethyl 3-formyl cyclopropane -1- carboxylate of (S) cyano 3-phenoxy benzyl, F = 1040C.

NMR spectrum (deutero chloroform) - peaks at 1.25 - 1.43 ppm attributed to the hydrogens of the twin methyls - peaks at 1.8 - 2.25 ppm attributed to the hydrogens in positions 1 and 3 of the cyclopropyl - peak at 6.4 ppm attributed to hydrogen carried by the same carbon as CN - peaks at 6.91 - 7.6 ppm attributed to hydrogens in aromatic rings - peaks at 9.8 - 9.9 ppm attributed to hydrogen formyl.

Stage F: 1R, cis 2,2-dimethyl 3- (2,2-dichloro vinyl) cyclopropane -1- carboxylate of (S) o-cyano 3-phenoxy benzyl
Into 25 cm3 of heptane are introduced 3.93 g of ground triphenyl phosphine, 1.12 g of ter-butanol, 1.7 g of potassium ter-butoxide, cooled to -10 ° C., added 1.9 g of chloroform , stirred for 1 hour at + 100C, added a solution of 3.49 g of 1R, cis 2,2-dimethyl 3-formyl cyclopropane -i- carboxylate of (S) p-cyano 3-phenoxy benzyl in 20 cm3 of tetrahydrofuran , agitates for 3 hours at + 100C, eliminates by filtration the insoluble material formed, adds to the filtrate 100 cm3 of a saturated aqueous solution of sodium phosphate, leaves to stand, decant, concentrates the organic phase to dryness by distillation under reduced pressure, chromatography the residue on silica gel, eluting with a mixture of benzene and cyclohexane (4/6), and obtains 3.4 g of IR, cis 2,2-dimethyl 3- (2,2-dichlorovinyl) cyclopropane - 1- (S) e-cyano 3-phenoxy benzyl carboxylate, F = 60 C.

NMR spectrum (deutero chloroform) - peaks at 1.18 - 1.23 p.p.m. attributed to the hydrogens of twin methyls - peaks at 1.8 - 1.93 p.p.m. and at 2.0 - 2.15 - 2.30 p.p.m.

attributed to the hydrogens in positions i and 3 of cyclopropane - peaks at 6.10 - 6.20 ppm attributed to Bthylenic hydrogen - peak at 6.33 ppm attributed to hydrogen carried by the same carbon as the CH group - peaks at 6.83 - 7.50 ppm attributed to hydrogens in aromatic rings.

Example 2: 1R, trans 2,2-dimethyl 3- (2,2-dichloro vinyl) cyclopropane -1- (S) -cyano 3-phenoxy benzyl carboxylate
Stage A: 1 R, trans 2,2-dimethyl 3-formyl cyclopropane -1 (cyclohexylamino) (cyclohexylimino) methylcarboxylate
2 cm3 of pyridine, 28.4 g of 1R acid, trans 2,2-dimethyl 3-formyl cyclopropane -1-carboxylic acid, are added to 300 cm3 of methylene chloride, 41.2 g of dicyclohexyl carbodiimide are added, the mixture is stirred for 1 hour at 200C and obtain a suspension of tR, trans 2,2-dimethyl 3-formyl cyclopropane -1carboxylate of (cyclohexylamino) (cyclohexylimino) methyl.

Stage 8: 7R, trans 2,2-dimethyl 3-formyl cyclopropane -1 (RS) -cyano 3-phenoxy benzylcarboxylate
To the suspension previously obtained, 30 g of RS-cyano 3-phenoxy benzyl alcohol are added, stirred for 16 hours at 20 ° C., eliminates by filtration the insoluble material formed, concentrates the filtrate to dryness by distillation under reduced pressure, chromatographs the residue silica gel, eluting with a mixture of benzene and ethyl acetate (95/5) and obtain 35 g of 1R, trans 2,2-dimethyl 3-formyl cyclopropane -1- (RS) -cyano carboxylate 3-phenoxy benzyl.

RMH spectrum (deutero chloroform) - peaks at 1.27 - 1.25 - 1.30 - 1.36 ppm attributed to the hydrogens of the twin methyls - peaks at 2.16 - 2.50 pp. Attributed to the hydrogens in function 1 and 3 of cyclopropyl - peak at 6.30 ppm attributed to hydrogen carried by the same carbon as the group -CN - peaks at 6.83 - 7.60 ppm attributed to hydrogens in aromatic rings.

Stage C: 1R, trans 2,2-dimethyl 3- (phenyimimethyl methyl) cyclopropane -1- (RS) -cyano 3-phenoxy benzyl carboxylate
In 100 cm3 of petroleum ether (eb 35 - 70CC), 4 g of aniline, 10 q of 1R, trans 2,2-dimethyl 3-formyl cyclopropane -1-IRIS carboxylate) -cyano 3-phenoxy are introduced benzyl, obtained in step 8 above, brings the reaction mixture to reflux by removing, by azeotropy, the water formed, concentrated to dryness by distillation under reduced pressure and obtains 14.4 g of 1R, trans 2,2-dimethyl 3- (phenylimino methyl) cyclopropane -1- carboxylate of (RS) oe-cyano 3-phenoxy benzyl crude benzyl used, such as for the following stage.

Stage D: IR, trams 2,2-dimethyl 3- (phenylimino methyl) cyclopropane -1- (S) -cyano 3-phenoxy benzyl carboxylate
40 cm3 of isopropanol are introduced: 1 cm3 of triethylamine, 14.4 g of 1R, trans 2,2-dimethyl 3- (phenylimino methyl) cyclopropane -1- (RS) α -cyano 3-phenoxy benzyl carboxylate obtained in stage C above, primer, stirred at 20 C for 96 hours, cools to -10 C, isolates, by wringing out the precipitate formed, dries it and obtains 8.7 g of 1R, trans 2,2-dimethyl 3 (phenyliminomethyl ) cyclopropane -1- carboxylate of (S) () - cyano 3-phenoxy benzyl, F = 94aC.

NMR spectrum (deutero chloroform) - peak at 1.32 ppm attributed to the hydrogens of the twin methyls - peaks at 2.30 - 2.65 ppm attributed to the hydrogens in positions 1 and 3 of cyclopropane - peak at 6.40 ppm attributed to hydrogen carried by the same carbon as CN-peaks at 7.66 - 7.76 ppm attributed to ethylenic hydrogen.

IR spectrum (chloroform) -1 - absorption at 1740 cm, attributed to the carbonyl of the ester -1 - absorption at 1640 cm, attributed to the conjugated CN group - absorptions at 1497 cm-1 and 1487 cm-1 attributed to the aromatic rings - absorption at 1382 cm-1 attributed to the twin methyls - absorption at 692 cm-1 attributed to the phenyl.

Stage E: IR, trans 2,2-dimethyl 3-formyl cyclopropane -1 (S) α -cyano 3-phenoxy benzylcarboxylate
5 g of 1R, trans 2,2-dimethyl 3- (phenylimino methyl) cyclopropane -1- (S) -cyano 3-phenoxy benzoyl carboxylate, stirred for 2 hours, are introduced into 100 cm3 of 2N aqueous hydrochloric acid solution and 30 minutes, at 20 ° C., isolates by wringing, the precipitate formed, dissolves it in methylene chloride, dries the solution, concentrates it to dryness by distillation under reduced pressure and obtains 4.2 g of 1R, trans 2.2 -dimethyl 3-fcrrnyi cyclopropane -1- carboxylate of (S) α -cyano 3-phenoxy benzyl, F = 700C.

NMR spectrum (deutero chloroform) - peaks at 1.26 - 1.29 ppm attributed to hydrogens of twin methyls - peak at 2.53 ppm attributed to hydrogens in positions 1 and 3 of cyclopropane - peak at 6.4 ppm attributed to hydrogen carried by the same carbon as the CN group - peaks at 6.90 - 7.50 ppm attributed to the hydrogens in the aromatic rings - peaks at 9.76 - 9.80 ppm attributed to the hydrogen in formyl
Stage F :: IR, trans 2,2-dimethyl 3- (2,2-dichlorovimyl) cyclopropane-1-carboxylate of (S) c-cyano 3-phenoxy benzyl
Into 25 cm3 of heptane are introduced 3.93 g of triphenyl phosphine, 1.12 g of tert-butanol, 1.7 g of potassium tert-butoxide, added at -100C, 1.8 g of chloroform, stirred for 1 hour at c150C, introduced at -200C, a solution of 3.5 g of 1R, trans 2,2-dimethyl 3-formyl cyclopropane -1- (S) -cyano 3-phenoxy benzylcarboxylate in 10 cm3 of tetrahydrofuran, stirred for 2 hours and 30 minutes at -10 ° C., poured the reaction mixture onto an aqueous solution of monosodium phosphate, extracted with ethyl ether, concentrated to dryness by distillation, chromatographed the residue on silica gel, eluting with benzene.

 3.4 g of 1R, trans 2,2-dimethyl 3- (2,2-dichlorovinyl) cyclopropane -1-carboxylate of (S) o-cyano 3-phenoxy benzyl are obtained.

NMR spectrum (deutero chloroform) - peaks at 1.18 - 1.24 ppm attributed to hydrogens in twin methyls - peaks at 1.60 - 1.70 ppm attributed to hydrogen in position I of cyclopropane - peaks at 2 , 20 - 2.29 - 2.30 - 2.40 ppm attributed to hydrogen in position 3 of cyclopropane - peaks at 5.58 - 5.70 ppm attributed to ethylenic hydrogen - peak at 6.43 ppm attributed to l hydrogen carried by the same carbon as the group -CN - peaks at 6.9 - 7.60 ppm attributed to the hydrogens of the aromatic rings
Example 3: 1R, trans 2,2-dimethyl 3-J (E | Z) Z-chloro 2-bromo
(S) -'- cyano 3-phenoxy ethenyll cyclopropane -1- carboxylate
benzyl
25 g of ground triphenyl phosphine, 9 g of potassium tert-butoxide, 6 g of tert-butanol are stirred into 130 cm 3 of heptane and stirred for 30 minutes at room temperature, adding a solution of 17 g of dibromo chlorine to OOC. methane in -40 cm3 of heptane, stirred for 45 minutes at 00 + 50, introduced to OOC, a solution of 17.6 g of tR, trans 2,2-dimethyl 3-formyl cyclopropane -1- carboxylate from (S) -cyano 3-phenoxy benzyl in 80 cm3 of tetrahydrofuran, stirred for 30 minutes at + 50C, pour the reaction mixture onto an aqueous solution N of sulfuric acid, extracted with ethyl acetate, washed with water, concentrated to dryness by distillation under reduced pressure, chromatographs the residue on silica gel, eluting with a mixture of benzene and cyclohexane (7/3), and obtains 16.5 g of 1R, trans 2,2-dimethyl 3-1 < EZ) 2-chloro 2-bromo ethenyl / cyclopropane -1- (S) -cyano 3-phenoxybenzyl carboxylate / = / D a +310 (c = O, o%, benzene)
Infrared spectrum (chloroform) -1 - absorption at 1738 cm attributed to the carbonyl of the ester - absorptions at 1585, 1485 cm1 attributed to the aromatic nuclei - absorptions at 1351, 1381 cm 1 attributed to the twin methyls
NMR spectrum (deutero chloroform) - peaks at 1.16 - 1.20 ppm attributed to hydrogens in twin methyls - peaks at 1.62 - 1.70 ppm attributed to hydrogen in position 1 of cyclopropane - peaks at 5.77 - 5.90 - 5.80 - 5.95 ppm attributed to ethylenic hydrogen - peak at 6.38 ppm attributed to hydrogen carried by the same carbon as the group -CN - peaks at 6.91 - 7.50 ppm attributed to hydrogens in aromatic rings.

Claims (11)

 10) As new industrial products, in all their stereoisomeric forms, the compounds of general formula (A)

 20) As new industrial products, in all their stereoisomeric forms, the compounds of general formula A according to claim 1, in which the alcoholic copula is of configuration (R S), namely 2,2-dimethyl-3-formyl cyclopropane-1-carboxylates of (RS) a-cyano-3-phenoxy benzyl.  30) As new industrial products, in all their stereoisomeric forms, the compounds of general formula A according to claim 1, in which the alcoholic copula is of configuration (S), namely the 2,2-dimethyl 3formyl cyclopropane-1-carboxylates of (S) a-cyano-3-phenoxy benzyl.  40) As new industrial products, in all their stereoisomeric forms, the compounds of general formula A according to claim 1, in which the alcoholic copula is of configuration (R), namely the 2,2-dimethyl-5-formyl cyclopropane-1-carboxylates of (R) a-cyano-3-phenoxy benzyl.  50) Process for the preparation of the compounds of general formula (A) as defined in claim 1 characterized in that a 2,2-dimethyl-3-formyl cyclopropane-1-carboxylic acid is reacted in trans form or in form of the lactone cis of a 2,2-dimethyl-3-dihydroxymethyl cyclopropane-1-carboxylic acid (II), with a dehydration reagent chosen from the group consisting of dicyclohexyl carbodiimide and diisopropyl carbodiimide, and in the presence of pyridine or 4-dimethyl aminopyridine, in a non-polar organic solvent, to obtain the 2,2-dimethyl 3-formyl cyclopropane-1-carboxylate of (cyclohexylamino) (cyclohexylimino) methyl or 2,2-dimethyl-3 -formyl cyclo propane-1-carboxylate (dtisopropylamino) isopropylimino) methyl, the acid copules of which are of trans or cis structure subjects one of these compounds to the action of alcohol (RS) acyano 3-phenoxy benzyl (III), in a non-polar solvent, to obtain 2,2-dimethyl 3-formyl cyclopropan e -1-carboxylate of (RSj a-cyano 3-phenoxy benzyl corresponding (A), of cis or trans structure, subjects, if desired within an apolar organic solvent, this racemic ester to the action of an amine primer of formula Z-NH2 in which Z represents the organic residue of a primary amine to obtain 2,2-dimethyl 3- (Z-iminomethyl) cyclopropane-I -carboxylate from (RS) a-cyano 3-phenoxy corresponding benzyl (IA), which is subjected to the action of a basic agent in a mixture of solvents in which the alcohol ester of one of the two configurations (R) or) is more soluble than its diastereoisomer, which allows, after epimerization of the benzylic center of the alcoholic copula to obtain, in crystalline form, the only ester corresponding to the configuration favored by insolubility (13), that is to say either 2 , 2-dimethyl 3- (Ziminomethyl) cyclopropane-1-carboxylate of (R) a-cyano 3-phenoxy benzyl or 2,2-dimethyl 3- (Z-iminomethyl) cyclopropane -1-carboxylate of (s) o ' -Cyan o 3-phenoxy benzyl, the acid copula of the compounds (IA) or Ig) having the same configuration as that of the starting compounds II, then subjects the compound of formula (Ig) to hydrolysis using an acid agent , to obtain, depending on the starting material used, either the 2,2-dimethyl-3-formyl cyclopropane-1-carboxylates of (s) acyano-3-phenoxy benzyl, or the 252-dimethyl-3-formyl.cyclopropane -l-earboxylates of (R) a-cyano-3-phenoxy benzyl of formula A.  60) Method according to claim 5 characterized in that the non-polar organic solvent in which the aldehyde compound (II) and the dehydrating reagent or the condensation compound and the alcohol (III) are reacted is chosen from the group consisting by aromatic hydrocarbons, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons and cyclohexane.  70) Method according to one of claims 5 or 6 characterized in that 11 primary amine which is reacted with the compound (IV) is aniline.  80) Method according to any one of claims 5 to 7 characterized in that the non-polar organic solvent within which the primary amine is reacted and the compound (IV) is chosen from the group consisting of aromatic hydrocarbons, hydrocarbons aliphatics, halogenated aliphatic hydrocarbons and cyclohexane.  90) Method according to any one of claims 5 to 7 characterized in that the basic agent to the action of which the ester (IA) of configuration alcohol (RS) is subjected is chosen from the group consisting of l ammonia, triethylamine, diethylamine, morpholine, pyrrolidine, piperidine, diisopropylamine, ephedrine, triethylenediamine, benzylamine, n-butylamine, sec-butylamine, tetrabutylammonium hydroxide, exchange resins ions with a strong basic character comprising quaternary ammoniums or amines, high molecular weight amines and, used in catalytic amount, soda, potash, alkali alcoholates, alkali amides, alkali hydrides, potassium terbutylate and sodium isopropyate.  100) Method according to any one of claims 5 to 9 characterized in that the solvent or the mixture of solvents within which the alcohol ester IA of configuration (RS) is reacted with the basic agent is chosen from the group consisting of acetonitrile, alkanols and mixtures of alkanols and petroleum ether.  110) Method according to any one of claims 5 to 10 characterized in that the acid agent used in the hydrolysis of the compound Ig is chosen from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid and paratoluene sulfonic acid.  120) Method according to claim il characterized in that the hydrolysis of the compound IQ is carried out in the presence of an organic solvent miscible with water.  13Q) As new intermediates necessary for the implementation of the process according to claim 5, in all their stereolayerous forms, the compounds of general formula (B)

 formula in which X represents a cyclohexyl or isopropyl group.  140) As new intermediates necessary for the implementation of the process according to claim 5, in all their steroisois forms, the compounds of general formula (B) according to claim 13s in which X represents a cyclohexyl radical, namely the 2,2-dimethyl 3-formyl cyclopropane-I -carboxylates of (cyclohexylamino) (cyclohexylimino) methyl don the acid copulas are of cis or trans configuration as well as the compounds of general formula (B) in which X represents an isopropyl radical namely 2,2-dimethyl-3-formyl cyclopropane-1-carboxylates (of isopropylamino) (isopropylimino) methyl whose acid copulas are of cis or trans configuration.