FR2662183A1 - Electrolytic process for the preparation of cyclopropane derivatives - Google Patents

Abstract

Process for the synthesis of a cyclopropane derivative, characterised in that a compound of formula I: in which R1 to R6 are hydrogen or non-electron-withdrawing organic groups is prepared by reaction of an olefin of formula II: with the product of electrolysis of a gem-dihalogenated compound of formula III: in which X1 and X2 are identical or different halogens chosen from the group consisting of chlorine, bromine and iodine, provided that, when X1 and X2 are chlorine, R5 or R6 are an aromatic organic group, the electrolysis of the compound III being performed in a noncompartmented electrolysis cell comprising a soluble zinc anode, followed by separation of the compound of formula I after reaction.

Description

 The present invention relates to an electrolytic process for the preparation of cyclopropane derivatives.

 The cyclopropane derivatives find today a more and more diversified use especially in pharmacy and in the phytosanitary field.

 Thus, many derivatives of chrysanthemic acid and analogues have long been used as insecticides including resmethrin, allethrin, permethrin and deltamethrin.

 Various volatile cyclopropanes are used as anesthetics including cyclopropane and aliflurane.

 Several morphinol derivatives have a cyclopropylmethyl substituent on nitrogen. In particular, it is buprenorphine, nalmefene and naltrexone with analgesic or narcotic antagonist properties.

 Some sedatives of the benzodiazepine family (prazepam, cyprazepam ...) carry the same type of substituent.

 Various substituted cyclopropylamines have various activities: insecticides (cyromazine), relaxants (cinflumide, lorbamate), and antibacterials (ciprofloxacin, enrofloxacin).

 Some arylcyclopropanes have antidepressant activity (rolycyprine, tranylcypromine, permethytyline).

 Finally, a large number of other active products have a cyclopropane structure, for example betaxolol (antihypertensive) or cicloprolol (antiadrenergic).

 The synthesis of these three-carbon rings is generally difficult.

 Two main methods are currently used, one based on the cyclization of difunctional molecules, cyclization of chlorobutyronitrile to cyanocyclopropane, for example, and the other on the methylenation of a double bond.

In this second method, the agent that is used for methylenation belongs to the carbene species and is most often derived from the decomposition of an azo derivative with removal of nitrogen, from the attack by a base of a polyhalogenated derivative or - the reduction of a geminated dihalide by a metal which is general
a carefully selected metal alloy.

 In some particular cases and in particular for the preparation of halogenated cyclopropanes, electrochemistry has also been used to generate the carbenic species by reduction of a gem-dihalogenated derivative.

 This electrochemical method is however limited to a few special cases. The reactions currently described mention the use of tetra or tri-halomethane for the synthesis of derivatives 1, 1-dihalocyclopropane or the use of activated olefins that is easily reducible as maleate or alkyl fumarates alkyl acrylates, alkyl cinnamates, that is to say olefins substituted with at least one electron-withdrawing group.

 As an illustration of this electrochemical method, mention may be made in particular of the following works which use tetra or trihalomethanes.

 In 1961, S. Wawzonek and R. C. Duty (J. Electroch, Soc 1961, 108, 1135) described the preparation of dichlorotetramethylcyclopropane by electroreduction of carbon tetrachloride in the presence of tetramethylethylene.

 In the same way, H.P. Fritz and W. Kornrumpf, (Liebigs Ann.

Chem. 1978, 1416-1423) added carbon tetrachloride on tri and tetra-methylethylene, on styrene and alphamethylstyrene. They further demonstrated that the same products could be obtained by replacing carbon tetrachloride with chloroform.

 T.K. Baryshnikova, M.E. Niyazymbetov, V.S. Bogdanov and V.A.

Petrosyan (Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pages 91-95, January 88, and No. 10 page 2325-7, October 1988) extended the scope of this reaction to various other olefins, but always from carbon tetrachloride.

 This dichlorocyclopropanation reaction is however not general, since T. Shono, Tet. Lett., 22, p. 871-4, 1981 showed that vinyl acetate was not converted into dichlorocyclopropane by this reaction.

 Finally, J. J. Yoshida, M. Yamamoto and N. Kawabata (Tet Lett.

26, 50, pages 6217-20, 1985) added dibromoindane dione to styrene, the gem-dihalogen derivative being activated by the presence of two ketone functions.

 With particular reference to cyclopropanation of activated olefins, MM Baizer and JL Chruma (J. Org Chem 37, 12, 1972 pages 1951-60) added carbon tetrachloride to diethyl fumarate, ethyl trichloroacetate on acrylonitrile, ethyl acrylate and diethyl maleate. These reactions were studied in aprotic solvents, in a compartmentalized electrolysis cell and equipped with a mercury cathode.

 More recently, Y.W. Lu, in his thesis, defended at the University of Paris Sud, Center d'Orsay, on May 26, 1989, showed the formation of cyclopropane derivatives, by reaction, in a cell of electrolysis, undivided and containing a soluble anode of aluminum, olefins activated with simple gem-dihalogenated derivatives.

 Thus, the processes described so far for the electrochemical synthesis of cyclopropane derivatives involve the use of either olefins activated by electron-withdrawing groups or the use of trichloromethane or carbon tetrachloride type derivatives or gem-dihalogenated derivatives comprising electron-withdrawing groups connected to the halogen-bearing atom, which activates the molecule.

 The object of the present invention is to be able to overcome the use of compounds activated by electron-withdrawing groups or halogens, and also to have easy access to cyclopropanes which do not contain halogens or directly connected electro-attractant groups. cyclopropane cycle.

dans laquelle R1 à R6 sont l'hydrogène ou des groupements organiques non électroattracteurs, par réaction d'une oléfine de formule Il

sur le produit d' électrolyse d'un composé gem-dihalogéné de formule III: :

dans laquelle X1 et X2 sont des halogènes, identiques ou différents, choisis dans le groupe constitué par le chlore, le brome et l'iode, à la condition que, lorsque X1 et X2 sont le chlore, R5 ou R6 soit un groupement organique aromatique, de préférence un groupement phényle, 1' électrolyse du composé III étant effectuée dans une cellule électrolytique non compartimentée et comportant une anode soluble de zinc, puis séparation du composé de formule I après réaction.More particularly, the present invention relates to a process for synthesizing a cyclopropane derivative, characterized in that a compound of formula I is prepared:

in which R1 to R6 are hydrogen or non-electroattractive organic groups, by reaction of an olefin of formula II

on the product of electrolysis of a gem-dihalogen compound of formula III:

wherein X1 and X2 are halogens, identical or different, selected from the group consisting of chlorine, bromine and iodine, provided that when X1 and X2 are chlorine, R5 or R6 is an aromatic organic group , preferably a phenyl group, the electrolysis of the compound III being carried out in a non-compartmentalized electrolytic cell and having a soluble anode of zinc, and then separation of the compound of formula I after reaction.

 By non-compartmentalized cell is meant a cell in which the anode and cathode compartments are not separated, and form a single compartment.

 Soluble anode means an anode which is consumed stoichiometrically during the electrochemical reaction of which it is the seat.

 It should be noted that the groups R1 to R6 can not be halogens since, by definition, an organic group comprises at least 1 carbon atom.

 Of course, it is preferable, for convenience, to provide that olefin II is present in the cell during the electrolysis of compound III but this is not essential, the olefin may be added during electrolysis or at the end of it.

 Among the non-electroattracting and electrochemically inactive organic radicals R 1 to R 6 which may be used, mention may be made of aliphatic or cyclic hydrocarbon radicals containing up to 30 carbon atoms but preferably from 1 to 10 carbon atoms, especially linear alkyl, alkenyl or alkynyl radicals. or branched, optionally having several double bonds and optionally substituted with radicals such as hydroxy, C 1 -C 7 alkoxy, phenoxy, substituted phenoxy or amino substantially substituted by one or more C 1 to C 7 hydrocarbon radicals, disubstituted alkoxy and amino radicals, aromatic C4 to C12 cyclic radicals, in particular the phenyl radical or cyclic radicals comprising one or more heteroatoms chosen from oxygen, sulfur and nitrogen.

 Among the olefins of formula II, mention will be made especially of allyl alcohol.

 For compounds of formula III, X 1 or X 2 are preferably chlorine or bromine, particularly bromine. The other substituents of this compound III have been defined previously. Among the preferred compounds, mention should be made of CH 2 Br 2.

 The operating conditions used according to the process of the present invention are soft and easily industrializable. Indeed, a moderate temperature, low cost solvents and a non-compartmentalized electrolysis cell are used.

 The cyclopropane derivatives are preferably obtained by electrolysis of a mixture of a gem-dihalogen derivative III and a non-activated olefin II in an aprotic or low-protic solvent, or a mixture of these solvents.

 Among the low protic solvents or their mixtures which can be used, mention should be made of acetonitrile and dimethylformamide. It is also possible to advantageously use methylene chloride containing about 10% of dimethylformamide. The medium can be made conductive by adding a bottom salt, preferably a tetraalkylammonium halide, especially tetraalkylammonium bromide or iodide.

 According to a preferred embodiment of the invention, a zinc salt is generated or introduced before the electrolysis of the geminated dihalogenated derivative. This speeds up the reaction. A simple technique is to electrolyse an easily reducible organic halide 2+ such as 1,2-dibromoethane, the anode then generating Zn ions, before adding the reagents into the electrolysis medium.

 In addition, when the non-activated olefin carries an acidic substituent, for example an alcohol, it is preferable to perform its pre-electrolysis in the presence of a halide.

 As regards the implementation of electrolysis, it is carried out using parameters known to those skilled in the art.

 The cathode, inert, is a conductive material whose nature does not matter. In particular, it is possible to use carbon, nickel or even stainless steel.

 The temperature is in general between 10 C and the boiling point of the solvent. It is preferably between 30 and 700C.

 We operate in general at constant intensity. In this case, the intensity of the electrolysis current generally corresponds to a cathodic current density of between 0.2 and 5 A / dm 2.

 However, it is also possible to operate at constant potential, or at variable intensity and potential.

 The reaction product I can be separated from the reaction mixture by known methods, in particular by liquid-liquid extraction, by chromatographic techniques or by exchange, as will be described in the examples.

 The examples given below will make it possible to demonstrate other advantages and characteristics of the present invention.

GENERAL PROCEDURE
In the examples below, unless otherwise indicated, the general procedure described below is used, the variations being specified in the result tables.

 A one compartment cell equipped with a zinc anode, a carbon fiber cathode, a refrigerant and kept under an argon stream is used. The solvent is a mixture of 22.5 ml of dichloromethane and 2.5 ml of dimethylformamide and the bottom salt is a mixture of 1.3 mmol (ie 5.10-2 2 M) of tetrabutyl bromide ammonium and 0.45 mmol (ie 2.10 2 M) of tetrabutyl ammonium iodide.

 The intensity of the electrolysis current is 200 mA and the temperature of the reaction medium varies from 35 to 40 ° C.

 The reagents are used in the following proportions: the ethylenic derivative 7.5 mmol at 10 mmol and the gem-dihalogen derivative of formula III 1.6 ml at 4 ml.

 An induction period of about 1 to 3 hours is observed. It takes 7 to 15 hours to observe cyclopropanation. This induction period can be suppressed by previously performing a pre-electrolysis lysis of 1,2-dibromoethane which allows the presence of Zn ions from the beginning of the electrolysis of the gem-dihalogen derivative III.

 For this purpose, 10 to 25 mmol of 1,2-dibro-ethane is electrolyzed so as to obtain 10 to 25 milliequivalents Zn 2 + after passing an amount of electricity from 2000 to 5000 C. The gem-dihalogen derivative III is then added. and the ethylenic derivative and the electrolysis is carried out.

 At the end of this electrolysis, the medium is hydrolysed with 50 ml of an aqueous ammonium chloride solution and then the cell is washed with 2 × 50 ml of diethyl ether. The mixture is stirred for half an hour and then allowed to settle.

 The aqueous phase is extracted with 3 x 50 ml of diethyl ether. The ethereal phases are then washed with 30 ml of an aqueous solution of sodium bicarbonate and 3 x 30 ml of an aqueous solution of sodium chloride.

 It is dried over MgSO4 and the solvents are distilled off.

A chromatography is then carried out on silica, eluting with either pure pentane or a diethyl ether / pentane mixture, so as to isolate the expected cyclopropane derivative, identified according to the usual methods of identification: Nuclear Magnetic Resonance,
Mass spectrometry and Infra-Red analysis.

EXAMPLE 1
Comparison of the process according to the invention with different methods of the state of the art
In order to compare the process according to the invention with the methods closest to the state of the art, cyclopropanation of cyclooctene and of CH 3 -CH = CH-CH 2 OH was carried out respectively from CH 2 Br 2.
The results obtained are presented in Table I below,
Test 1 corresponding to the aforementioned method of YW LU, (thesis of
University Paris XI, 1989), test 2 corresponding to the above methods of VA PETROSYAN and HP FRITZ (Liebigs Ann Chem 1978, 1416), and tests 3 to 6 to the process according to the invention, with anodes of various natures.

 These results confirm that only the process according to the invention, using zinc as anode, leads to the expected cyclopropane derivatives.

TABLE I

<SEP> Olefin <SEP> of <SEP> CH2Br2 <SEP> Comparti <SEP> Yield <SEP> Quantity <SEP> Duration <SEP> of
<tb> Test <SEP> formula <SEP> II <SEP> (equiv.) <SEP> Solvent <SEP> Salt <SEP> from <SEP> background <SEP> Anode <SEP> Cathode <SEP> ments <SEP > in <SEP> product <SEP> electricity <SEP> electrolysis
<tb><SEP> (mmol.) <SEP> cell <SEP> isolated <SEP> (%) <SEP> (c) <SEP> (h)
<tb> 1 <SEP> cyclooctene <SEP> 5 <SEP> NMP <SEP> NBu4BF4 / I <SEP> Al <SEP> Inox <SEP> 1 <SEP> 0 <SEP> 10 <SEP> 000 <SEP> 14
<tb><SEP> (10) <SEP> (10-2 <SEP> M / 2.10-2 <SEP> M)
<tb> 2 (*) <SEP> cycloctene <SEP> 5 <SEP> CH2Cl <SEP> NBu4BF4 / I <SEP> Pb <SEP> Pt <SEP> 2 <SEP> 0 <SEP> 5 <SEP> 000 <SEP> 9
<tb><SEP> (10) <SEP> (0.35 <SE> M)
<tb> 3 <SEP> cyclooctene <SEP> 5 <SEP> CH2Cl / DMF <SEP> NBu4BF4 / I <SEP> Zn <SEP> carbon <SEP> 1 <SEP> 64 <SEP> 10 <SEP> 000 <SEP > 14
<tb><SEP> (10)
<tb> 4 <SEP> CH3-CH-CH-CH2OH <SEP> 3,4 <SEP> CH2Cl / DMF <SEP> NBu4BF4 / I <SEP> Al <SEP> carbon <SEP> 1 <SEP> 0 <SEP > 5 <SEP> 000 <SEP> 7
<tb><SEP> (7.85)
## STR2 ## > 5 <SEP> 000 <SEP> 7
<tb><SEP> (7.5)
<tb> 6 (**) <SEP> CH3-CH-CH-CH2OH <SEP> 3,4 <SEP> CH2Cl / DMF <SEP> NBu4BF4 / I <SEP> Cu <SEP> carbon <SEP> 1 <SEP > 0 <SEP> 5 <SEP> 000 <SEP> 7
<tb><SEP> (7.5)
<tb> * I 150 mA ** CH2Br2 is not reduced; copper deposit at the cathode
EXAMPLE 2
Variation of the various parameters of the process according to the invention.

On a control reaction, the cyclopropanation of the compound CH3 CH = CH-CH2OH or CH2 = CH-CH2OH, it was observed the influence of the nature of the cathode, the solvent, the halogen atoms of the geminated dihalogen derivative and of the presence of Zn2 + ions before the electrolysis of the gem-dihalogenated derivative
The results obtained for each of these tests are shown in Tables II, III, IV and V.

1- Influence of the nature of the cathode
Each of the tests shown in Table II was performed without pre-electrolysis.

2- Influence of the nature of the solvent
Electrolysis reactions were performed without pre-electrolysis, and the results obtained are shown in Table III.

3- Influence of the nature of halogen in the gem-dihalogenated derivative
The results are shown in Table IV.

 The test carried out with the CH 2 BrCl derivative was carried out with a pre-electrolysis at 5000 C of 20 mmol. BrCH2-CH2-Br.

4- Influence of the presence of Zn2 + ions before the electrolysis of the gem-dihalogenated derivative
The results are shown in Table V.

TABLE II

Olefin <SEP> of <SEP> Derivative <SEP> gem <SEP> Time <SEP> of <SEP> Yield <SEP> in
<tb> formula <SEP> II <SEP> dihalogenous <SEP> Cathode <SEP> electrolysis <SEP> derivative <SEP> cyclopropanic
<tb> (mmol) <SEP> (equiv) <SEP> (h) <SEP> (%)
<tb> CH2 = CH-CH2OH <SEP> CH2Br2 <SEP> carbon <SEP> 18.5 <SEP> 42 <SEP> (**)
<tb><SEP> (25) <SEP> (2.5)
<tb> CH2 = CH-CH2OH <SEP> CH2Br2 <SEP> Inox <SEP> 24 <SEP> 42 <SEP> (**)
<tb><SEP> (25) <SEP> (2.4)
<tb> CH3-CH = CH-CH2OH <SEP> CH2Br2 <SEP> carbon <SEP> 7 <SEP> 56
<tb><SEP> (7.55) <SEP> (3.4)
<tb> CH3-CH = CH-CH2OH <SEP> CH2Br2 <SEP> Inox <SEP> 8.5 <SEP> 50 <SEP> (*)
<tb><SEP> (7.55) <SEP> (3.2)
<tb> * A deposition of zinc ** is observed in the form of acetate (acetoxymethyl) cyclopropane.After stopping the electrolysis, 6 ml of anhydrous
acetic acid and 4 ml of pyridine; let it shake for an hour. It is hydrolyzed and extracted with pentane.

TABLE III

Olefin <SEP> of <SEP> Derivative <SEP> gem <SEP> Time <SEP> of <SEP> Yield <SEP> in
<tb> formula <SEP> II <SEP> dihalogenous <SEP> Solvent <SEP> electrolysis <SEP> derived <SEP> cyclopropanic
<tb> (mmol) <SEP> (equiv) <SEP> (h) <SEP> (%)
<tb> CH3-CH = CH-CH2OH <SEP> CH2Br2 <SEP> CH2Cl2 / DMF <SEP> 7 <SEP> 56 <SEP> 94 <SEP> (*)
<tb><SEP> (7.55) <SEP> (3.4)
<tb> CH3-CH = CH-CH2OH <SEP> CH2Br2 <SEP> CH3CN <SEP> 7 <SEP> 40
<tb><SEP> (7.55) <SEP> (3.3)
<tb> CH3-CH = CH-CH2OH <SEP> CH2Br2 <SEP> DMF <SEP> 11 <SEP> 38 <SEP> 68 <SEP> (*)
<tb><SEP> (7.55) <SEP> (7.9)
<tb> * The second yields indicated by an asterisk are the returns determined by
chromatographic analysis (GC) prior to isolation of the cyclopropane derivative TABLE IV

Olefin <SEP> of <SEP> Derivative <SEP> gem <SEP> Time <SEP> of <SEP> Yield <SEP> in
<tb> formula <SEP> II <SEP> dihalogenous <SEP> electrolysis <SEP> derivative <SEP> cyclopropanic
<tb> (mmol) <SEP> (equiv.) <SEP> (h) <SEP> (%)
<tb> CH3-CH = CH-CH2OH <SEP> CH2BrCl <SEP> 6.5 <SEP> 54
<tb><SEP> (7.55) <SEP> (2.6)
<tb> CH3-CH = CH-CH2OH <SEP> CH2Br2 <SEP> 7 <SEP> 56
<tb><SEP> (7.55) <SEP> (3.4)
<tb> TABLE V

Olefin <SEP> of <SEP> Derivative <SEP> gem <SEP> Time <SEP> of <SEP> Yield <SEP> in
<tb> formula <SEP> II <SEP> dihalogenous <SEP> electrolysis <SEP> derivative <SEP> cyclopropane <SEP> Observations
<tb> (mmol) <SEP> (equiv.) <SEP> (h) <SEP> (%)
<tb> CH3-CH = CH-CH2OH <SEP> CH2Br2 <SEP> 7 <SEP> 56 <SEP> 94 <SEP> (*) <SEP> without <SEP> preelectrolysis
<tb><SEP> (7.55) <SEP> (3.4)
## STR5 ##
<tb><SEP> (20) <SEP> (2.5) <SEP> 20 <SEP> mmol. <SEP> BrCH2CH2Br
<tb><SEP> (I <SEP> = <SEP> 230 <SEP> mA)
<tb> CH3-CH = CH-CH2OH <SEP> CH2Br2 <SEP> 7 <SEP> 44 <SEP> 74 <SEP> (*) <SEP> without <SEP> preelectrolysis
<tb><SEP> (20) <SEP> (1.5) <SEP> 20 <SEP> mmol. <SEP> CH2 = CH-CH2Br
<tb><SEP> the olefin <SEP> being <SEP> already
<tb><SEP> present <SEP> (I <SEP> = <SEP> 250 <SEP> mA)
<tb> * The yields indicated by an asterisk correspond to the yields determined by GC chromatographic analysis before isolation of the expected cyclopropane derivative.
It is thus demonstrated, in particular, that the nature of the cathode has no influence on the cyclopropanation reaction according to the invention, as well as the nature of the halogen atoms in the geminated dihalogen derivative.

EXAMPLE 3
Preparation of various cyclopropane derivatives from CH2Br2 or CH2BrCl
The results obtained are shown in Table VI.

TABLE VI

<SEP> Returns
<tb> Olefin <SEP> of <SEP> Derivative <SEP> gem <SEP> Pre- <SEP><SEP> Duration of <SEP> Derived
<tb> formula <SEP> II <SEP> dihalogenous <SEP> electrolysis <SEP> electrolysis <SEP> cyclopropane <SEP> Analysis <SEP> Products
<tb> (mmol) <SEP> (equiv.) <SEP> (C) <SEP> (h) <SEP> obtained <SEP> CPG <SEP> (%) <SEP> isolated <SEP> (%)
<tb> Cyclooctene <SEP> CH2Br2 <SEP> - <SEP> 14 <SEP> Bicyclo [6.1.0] nonane <SEP> 65 <SEP> 64
<tb> (10) <SEP> (5)
<tb> Octene-1 <SEP> CH2Br2 <SEP> - <SEP> 14 <SEP> n-hexylcyclopropane <SEP> 69 <SEP> 66
<tb> (9) <SEP> (5)
<tb> Styrene <SEP> CH2Br2 <SEP> yes <SEP> 11 <SEP> Phenylcyclopropane <SEP> 30 <SEP> 26
<tb> (7.4) <SEP> (4,5) <SEP> (2500)
<tb> 1,3-cyclo- <SEP> CH2Br2 <SEP> yes <SEP> 14 <SEP> Trans-tricyclo- <SEP> 66 <SEP> (*)
<tb> octadiene <SEP> (6) <SEP> (7) <SEP> (4000) <SEP> [7.1.0.02.4] decane
<tb> Cyclohex-2- <SEP> CH2BrCl <SEP> yes <SEP> 4 <SEP> Cis-bicyclo [4.1.0] <SEP> 75
<tb> en-1-ol <SEP> (6.7) <SEP> (2.5) <SEP> (4000) <SEP> heptanol-2
<tb> TABLE VI (Continued)

Trans-Butene- <SEP> CH2Br2 <SEP> - <SEP> 7 <SEP> Trans (hydroxymethyl) <SEP> 94 <SEP> 56
<tb> 2-ol-1 <SEP> (3.4) <SEP> 1-methyl-2-cyclo (7.55) <SEP> propane
<tb> Propene-2-ol-1 <SEP> CH2Br2 <SEP> - <SEP> 19.7 <SEP> (Acetoxymethyl) - <SEP> 42 <SEP> (**)
<tb> (25) <SEP> (2.5) <SEP> cyclopropane
<tb> Trans-phenyl-3- <SEP> CH2BrCl <SEP> yes <SEP> 6.75 <SEP> Trans- (hydroxymethyl) <SEP> 59
<tb> propene-2-ol-1 <SEP> (4) <SEP> (4000) <SEP> 1-phenyl-2-cyclo (6) <SEP> propane
<tb> 2,3-dihydropyran <SEP> CH2Br2 <SEP> yes <SEP> 9 <SEP> oxa-2-bicyclo [4.1.0] - <SEP> 72 <SEP> 54
<tb> (7.7) <SEP> (4) <SEP> (2700) <SEP> heptane
Phenyl allyl ether <SEP> CH 2 Br 2 <SEP> yes <SEP> 10 <SEP> (Phenoxymethyl) cyclo <SEP> 50
<tb> (5.1) <SEP> (7) <SEP> (4000) <SEP> propane
<tb> TABLE VI (Continued)

Geraniol <SEP> CH2Br2 <SEP> or <SEP> 5.5 <SEP> Trans- (hydroxymethyl) <SEP> 70
<tb> (6.9) <SEP> (2.9) <SEP> (4000) <SEP> 1-methyl-2- (methyl)
<SEP> 4-pentenyl-3) 2-cyclo
<SEP> propane
<tb> (CH3) 2C = CHCl <SEP> CH2Br2 <SEP> yes <SEP> 9 <SEP> Not <SEP> from <SEP> reaction <SEP> - <SEP> (9.2) <SEP> (4 , 3) <SEP> (4000)
<tb> * Passage through a monocyclopropane intermediate ** Ispöé in the form of acetate. After stopping the electrolysis, 6 ml of acetic anhydride and 4 ml of pyridine are added; let it shake for an hour. It is hydrolyzed and extracted with pentane.

 The test carried out with the olefinic derivative (CH 3) 2 = CHCl was carried out as a comparative test. It does not meet the definition of formula II. It shows that, surprisingly, the reaction does not occur when the olefin carries a halogen directly attached to a carbon of the double bond.

EXAMPLE 4
Preparation of Cyclopropanic Derivatives Using C 2 (CH 3) 2 Br 2 as a Gemdihalogenated Derivative
The corresponding results are shown in Table VII below.

TABLE VII

Olefin <SEP> of <SEP> Time <SEP> of <SEP> Derivative <SEP> cyclopropane <SEP> Yield
<tb> formula <SEP> II <SEP> C (CH3) 2Br2 <SEP> Preelectrolysis <SEP> the electrolysis <SEP> formed <SEP> into <SEP> product
<tb> (5 <SEP> mmol.) <SEP> (equiv.) <SEP> (C) <SEP> (h) <SEP> isolated <SEP> (%)
<tb> Trans-Butene-2-ol-1 <SEP> (5) <SEP> 4000 <SEP> 6 <SEP> Trans- (hydroxymethyl) -1- <SEP> 51
<tb><SEP> trimethyl-2,2,3-cyclo
<SEP> propane
<tb> Methyl-3-butene-2-ol-1 <SEP> (3,7) <SEP> 4000 <SEP> 5 <SEP> (Hydroxymethyl) -1-tetra- <SEP> 53
<tb><SEP> methyl-2,2,3,3-cyclo
<SEP> propane
<tb> Cyclooctene <SEP> (10) <SEP> 4000 <SEP> 16 <SEP> Dimethyl-9,9-bicyclo- <SEP> 46
<tb><SEP> [6,1,0] nonane
<Tb>
EXAMPLE 5
Preparation of Cyclopropane Derivatives from Different Dihalogenated Geminate Derivatives and Cyclooctene

 The corresponding cyclopropanation reactions were carried out from 4 mmol of cyclooctene.

 Only the tests carried out with Ph-CH-C12 or Ph-CH-B r2 as a gem-dihalogenated derivative correspond to the process according to the invention. The other tests were carried out as comparative tests, the gem-dihalogen derivative not satisfying the definition of formula III.

 The results are shown in Table VIII below.

These results show that, surprisingly, cyclopropanation of cyclooctene is observed only in the case where a non-activated geminate dihalogen derivative of formula III according to the invention is used. TABLE VIII

<SEP> gem-dihalogenated derivative <SEP> Preelectrolysis <SEP><SEP><SEP><SEP> cyclopropanic <SEP><SEP><SEP>
<tb><SEP> (equiv.) <SEP> (C) <SEP> electrolysis <SEP> obtained <SEP> prodult <SEP> isolated <SEP> (%)
<tb><SEP> (h)
<tb> Ph-CH-Cl2 <SEP> (10) <SEP> yes <SEP> (3000) <SEP> 15 <SEP> (150 <SEP> mA) <SEP> Phenyl-9-bicyclo [6.1.0 ] nonane <SEP> 20
<tb> Ph-CH-Br2 <SEP> (7) <SEP> yes <SEP> (4000) <SEP> 10 <SEP> (150 <SEP> mA) <SEP> Phenyl-9-bicyclo [6.1.0 ] nonane <SEP> 27
<tb> Ph-C-Cl3 <SEP> (7) <SEP> yes <SEP> (4000) <SEP> 7 <SEP> (200 <SEP> mA) <SEP> 0 (*)
<tb> Cl2-CH-CO2-Me <SEP> (12) <SEP> yes <SEP> (4000) <SEP> 22 <SEP> (200 <SEP> mA) <SEP> 0 (*)
<tb> Br2-CH-CO2-Me <SEP> (5) <SEP> yes <SEP> (4000) <SEP> 3 <SEP> (200 <SEP> mA) <SEP> 0 (*)
<tb> Br2-CH-CO2-Me <SEP> (**) <SEP> - <SEP> 4 <SEP> (200 <SEP> mA) <SEP> 0 (*)
<tb> Cl3-C-CO2-Me <SEP> (5) <SEP> yes <SEP> (4000) <SEP> 6 <SEP> (200 <SEP> mA) <SEP> 0 (*)
<tb> * There is no disappearance of cyclooctene.

** This test was performed using a copper anode.

EXAMPLE 6
In this case, the addition of the non-activated olefin II is carried out after electrolysis of the gem-dihalogen derivative III.

The procedure is as follows:
In a mixture of 25 ml of dichloromethane and 2 ml of
DMF, made conductive by the presence of 400 mg of NBu4Br and 200 mg of NBu4I, 40 mmol of CH2Br2 is electrolyzed at 40 ° C.

Following this electrolysis, 5.9 mmol of
CH3CH = CH-CH2OH and the whole is stirred for 8.5 h.

 28% of (hydroxymethyl) -1-methyl-2-cyclopropane are then isolated from the starting olefin.

 In an identical process, cyclopropanation of styrene (6 mmol) was carried out. In this case, 14% of phenylcyclopropane is isolated from the starting styrene.

Claims (10)

 1. Process for the synthesis of a cyclopropane derivative, characterized in that a compound of formula I is prepared

 in which R1 to R6 are hydrogen or non-electroattractive organic groups, by reaction of an olefin of formula II

 on the product of electrolysis of a gem-dihalogen compound of formula III:

 wherein X1 and X2 are halogens, identical or different, selected from the group consisting of chlorine, bromine and iodine, provided that when X1 and X2 are chlorine, R5 or R6 is an aromatic organic group , preferably a phenyl group, the electrolysis of the compound III being carried out in a non-compartmentalized electrolytic cell, and comprising a soluble anode of zinc, and then separation of the compound of formula I after reaction.  2. Method according to claim 1, characterized in that the electrolysis of the compound of formula III in mixture with the olefin of formula II.  3. Method according to one of claims 1 and 2, characterized in that X1 and X2 represent chlorine or bromine.  4. Method according to one of claims 1 to 3, characterized in 2+ that the medium already contains Zn ions before the electrolysis of the compound of formula III.  5. Method according to one of claims 1 to 4, characterized in that the electrolysis is carried out in an aprotic solvent or slightly protic or a mixture of these solvents.  6. Process according to claim 5, characterized in that the solvent is chosen from acetonitrile, dimethylformamide, methylene chloride or mixtures thereof.  7. Method according to one of claims 1 to 6, characterized in that as a conductor used a bottom salt which is preferably a tetraalkyl ammonium halide.  8. Method according to one of claims 1 to 7, characterized in that one operates at constant intensity using an electrolysis intensity which corresponds to a cathodic current density of between 0.2 and 5 A / dm2.  9. Method according to one of claims 1 to 8, characterized in that the compound III is dibromomethane.  10. Process according to any one of claims 1 to 9 characterized in that the olefin of formula II is allyl alcohol.