DE3147105A1 - Process for the preparation of cyclopropane derivatives - Google Patents

Description

Process for the production of cyclopropane

Derivatives

10

15th

The invention relates to a process for the preparation of cyclopropane derivatives.

DE-OS 2,639,777 describes a multistage process for the preparation of 2- (2,2-dihalovinyl) -3,3-dimethylcyclopropane-carboxylic acid specified. This acid is a valuable intermediate product, especially in the cis form for the production of insecticidal compounds. The procedure specified there will work out of a compound of the formula

in which X has different meanings. An example of this is trans-ethyl ^ -acetyl ^^ - dimethylcyclopropane carboxylate and remains in the method described there, unless a special one Isomerization stage is introduced, the geometry

this connection. Indeed, the isomerization is either of the starting material or any intermediate in the process extremely difficult, as in the OS example-.5 isomerization indicated, in which the trans compound is only converted into a 70:30 trans: ei s-Ge-r mixed could be converted. Obviously, this is a very unsatisfactory way of making the cis link.

10

It has now been shown that starting materials of the type specified in DE-OS 2,639,777 are reacted in this way can be that either cis or trans compounds arise, as desired.

The present invention relates to a method for Preparation of a compound of the general formula

20th

1 2
in which R and R each independently represent a hydrogen atom or an alkyl group with up to

12th

10 carbon atoms, or R and R together represent an alkylene group having 2 to 5 carbon atoms, or an alkali or alkaline earth salt of that. The process is characterized in that an ester of the general formula

(II)

/ 3

1A-55 414 -y-CV "'" 3U7105

1 2

in which R and R are those for the general formula I.

have given meaning and R ^ an optionally substituted alkyl group means with a hypochlorite or hypobromite of an alkali or earth r Reacts alkali metal in the presence of water.

1 2
R and R can be the same or different

but preferably the same. Preferably R is and

R is in each case an alkyl group with 1 to 4, particularly 1 or 2 carbon atoms, are particularly preferred

1 2
R and R are each methyl groups.

The group R ^ preferably has up to 6, in particular up to 4 carbon atoms in the alkyl group and those optionally present on the alkyl group Substituents can e.g. B. be selected from halogen atoms, alkoxy groups and phenyl groups. Preferably

■ τ.

R ^ means an unsubstituted alkyl group, in particular a primary or secondary group, especially a methyl or ethyl group.

In the method according to the invention, a hypochlorite or hypobromite of an alkali or alkaline earth metal, z. B. of sodium, potassium, calcium, magnesium or barium used. Preferably a hypochlorite, especially sodium hypochlorite is used.

The hypochlorite or hypobromite can be used where appropriate is, to the reaction mixture in the form of a solid (e.g. calcium hypochlorite) or as an aqueous Solution can be added or it can be formed in situ, conveniently by adding elemental Chlorine or bromine to an aqueous solution or suspension of an alkali or alkaline earth metal hydroxide. So is the case with a preferred embodiment of the process according to the invention, the compound of general formula II with

/ 4

1A-55 414 "" - / <> / '"' ^: 3U7105

an alkali or alkaline earth metal hydroxide in the presence of water and optionally one or more additional ones Solvents or diluents are mixed and elemental chlorine or bromine is added in measured amounts to the resulting reaction mixture was added.

The inventive method is preferably carried out at a temperature in the range of -10 to +80 ⁰ C. In general, it is preferred to start the reaction at a temperature in the range of -10 to +20 ⁰ C, to the formation of undesirable halogen compounds should be avoided. In particular, when the hypochlorite or hypobromite is formed in situ, as described above, it is preferably the reaction mixture initially at low temperature, e.g. B. -10 to +20 ⁰ C, preferably -5 to 15 ⁰ C and in particular -5 to 5 ° C to keep the formation of chlorate or bromate instead of hypochlorite or hypobromite as low as possible. It can be advantageous to increase the temperature of the reaction mixture after an initial reaction time in order to accelerate the reaction to complete.

The process according to the invention is carried out in the presence of water. In general, it is preferred that an inert organic solvent is also present to dissolve the starting materials support. This additional solvent can be wholly or partially miscible with water, e.g. B. an alcohol such as ethanol or it may be immiscible with water, e.g. B. a hydrocarbon such as toluene or benzene. In the latter case it is possible that a phase transfer catalyst e.g. B. tetrabutylammonium chloride is applied.

The molar ratio of the reactants is not critical. In general, however, it is preferred

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to use an excess of hypochlorite or hypobromite compared to the compound of general formula II. Preferably the molar ratio is Hypochlorite or hypobromite to the compound of the general formula II in the range from 3: 1 to 7: 1, in particular from 3.5: 1 to 5: 1.

Depending on the exact reaction conditions, a mono- or dialkali or eealkali salt of the acid is used of the general formula I formed. If the free acid is to be produced, this can be done according to the usual Work-up process can be obtained under acidic conditions.

The starting material of the general formula II occurs in the form of isomers in which the CH ^ CO- and

χ ->

the -CO ₂ R group is cis or trans to one another

can. The relative proportion of these cis and trans isomers in the starting material depends on how the starting substance has been produced. For example, in the process of DE-OS 2,639,777 for the preparation of a compound of the formula II, in

1 2
the R and R both represent methyl groups in which

a sulfur ylide of the formula (CH _x ) _o S ⁺ - ~ CH-C0 _Q R ³ with

JC .. C-

the mesityl oxide (CH -,) pC = CH-CO-CH _{3 is} converted, almost exclusively the trans isomer is obtained. In the context of this description and the claims, the terms cis and trans relate exclusively to the relative positions of the CH ^ CO and the -CO ₉ R groups.bzw. of the groups they have been converted into. There may of course be other isomers, e.g. B.
have borrowed meanings.

1 2

Isomers occur, e.g. B. if R and R are different

The process of the invention can be carried out using a cis or trans starting material or a mixture thereof and im

/ 6

1A-55 414 -J ^ -f, "" ^: 3H7105

generally the configuration is retained in the acid obtained. The resulting acid or that Salt, whatever its configuration, can then easily be converted into the corresponding one cis-anhydride of the formula

(III)

1 2
in which R and R have the meaning given above «

Thus, a preferred embodiment of the method according to the invention also includes the additional one Step of converting the resulting acid of the formula I or its alkali or alkaline earth metal salt into the corresponding cis-anhydride of the formula III.

A cis acid of the formula I or an alkali or Alkaline earth salts thereof can easily be converted into the cis-anhydride of the formula IEE according to known methods Procedure, e.g. B. by gentle warming or by treatment with a dehydrating agent, z. B. phosphorus trichloride or acetic anhydride. 25th

The trans acid or its salt must be treated with somewhat harsher processes in order to achieve isomerization to the cis-anhydride of the formula III, e.g. B. by converting at least one • 30 of the carboxy groups in an 'acyl halide group or in an anhydride group and subsequent thermal initiation of isomerization with formation of the cis-anhydride of formula III.

Ii

An anhydride group can be one with another molecule of the cyclopropane diacid itself, arose z. B, by heating or by reaction with a dehydrating agent. However, it is preferably a mixed anhydride because the thermal Isomerization of a mixed anhydride generally takes place at a lower temperature than it is necessary for an anhydride of cyclopropanoic acid itself.

The conversion (functionalization) of the carboxy group (s) into an acyl halide group or an anhydride group can be carried out by known methods, e.g. B. by reaction with a phosphorus halide or oxyhalide or sulfur oxyhalide or the acyl halide or anhydride of an alkanoic acid, advantageously one with up to 4 carbon atoms in the or in each alkyl group. Suitable reagents include PCI, PCl ₅ , POCl ₅ , SOCl ₂ , CH ₃ COCl

and (CEUCO) pOo The use of acetic anhydride or acetyl chloride is preferred. In some cases, the functionalization can be carried out under certain conditions in which an isolation of the acyl halide or anhydride occurring as an intermediate is not required "

The temperature required to initiate the isomerization depends on which functional Derivative of the acid has been formed. In space-.

but a temperature of at least 130 ° C, preferably at least 160 ⁰ C is ordinary applied. This temperature can be reached e.g. B. by heating the functional derivative in the presence of a low-boiling solvent under pressure, by heating the functional derivative in the presence of a high-boiling solvent or by evaporating the

/8th

functional derivative. So can ζ. B. the trans-acid I or an alkali or Erdnlkalisalz thereof in one Alkanoic acid halide or enhydride are dissolved, the serves as both a reagent and a solvent, e.g. B. acetyl chloride or acetic anhydride, and that Mixture can be heated under pressure in a sealed tube or an autoclave to allow evaporation of the solvent. Optionally, the functional derivative can either be formed beforehand or formed in situ in a solvent with a boiling point at or above the desired temperature and dissolved under atmospheric pressure to the desired temperature can be heated. Any aprotic, high-boiling solvent that opposes inert to the reaction products can be used for this purpose. For example, N-methylpyrrolidone has been found proved suitable.

Another means of initiating thermal isomerization comprises introducing the functionalized trans compound, if appropriate in the presence of an inert Solvent in a hot reaction zone, which is preferably contains an inert contact material. Under these conditions, evaporation and isomerization occur.

The functional starting material, optionally in an inert solvent, e.g. B. toluene, xylene or petroleum ether can be dissolved, can be pumped into the reaction zone or with the aid of a carrier gas, which can be one of the above-mentioned solvents in gaseous form or which can be an inert gas such as nitrogen. The reaction zone, which is preferably heated to a temperature between 250 and 350 ° C., is conveniently packed with an inert contact material, which is preferably a mechanically strong material with good thermal conductivity. Glass, oC aluminum and carborundum are suitable for this.

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1A-55 414 ~ ⁹ ^ 'α 3Η7105

By suitable choice of the reaction conditions, it is possible to start the reaction from the compound of the general formula II to carry out with the formation of the cis-anhydride of the formula III, without the as Acid I or a salt thereof occurring as an intermediate product must be isolated and / or purified.

The resulting compound of general formula III can be converted in many ways into a corresponding cis 2- (2,2-dihalovinylJ-cyclopropanecarboxylic acid. In the following, a number of reactions are given by way of example. For the sake of simplicity, only the preparation of the 2- (2 , 2 _T dichlorovinyl) -3,3-dimethyl-cyclopropanecarboxylic acid, but similar processes can also be used for the preparation of other compounds.

(A) The anhydride of the formula III is reacted with sodium trichloroacetate preferably at a temperature in the range from -60 to 60 ^° C. in the presence of a solvent such as acetonitrile to form an equilibrium mixture of cis-2-trichloroacetyl-3,3-dimethylcyclopropanecarboxylic acid and its Lactol tautomer.

(b) The mixture of tautomers is made with sodium borohydride in an aprotic solvent such as Dimethylformamide reacted at elevated temperature to form a lactone of the formula:

HCl ₂ C

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1A-55 414 """ ¹ ^ Vi""" 3U7105

(c) The lactone is treated with a strong base, ζ. Β. Potassium tert-butoxide reacted in dimethyl sulfoxide with formation of the desired cis-2- (2,2-dichlorovinyl) -3,3-dimethyl-cyclopropanecarboxylic acid. 5

The trans connection can be established as follows will:

(a) The mixture of tautomers obtained in step (a) above is made with phosphorus trichloride and zinc in the presence of an inert polar solvent such as dimethylformamide converted to form a lactone of the formula:

0

Cl ₀ C = / V = 0

u ₂ v

HäC ^^^ vCH-,

(b) The lactone is in alkaline conditions in Hydrolyzed in the presence of methanol, with the formation of trans ^ -Dichloracetyl ^^ - dimethyl-cyclopropanecarboxylic acid methyl ester.

(c) This is to the corresponding alcohol trans-2- (2,2-dichloro-1-hydroxyethyl) -3,3-dimethyl-cyclo- methyl propanecarboxylate reduced.

(d) The alcohol is reacted with tris (dimethylamine) phosphine (N (CHU) ₂ ) ^ P and carbon tetrachloride

with formation of the trans-ester trans-2- (2,2-dichlorovinyl) -3,3-dimethylcyclopropanecarboxylic acid methyl ester, which can be hydrolyzed under known conditions to form the corresponding trans acid.

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1A-55 414-1-p-- ν, / '-'"■ 3H7105

The invention therefore also relates to a process for the preparation of a compound of the general formula:

Hal ₂ C = C;

(XI)

in the shark each independently a fluorine, Means chlorine or bromine atom. In these processes, a compound of the general formula II is converted into a Compound of the general formula I or a salt thereof converted with the aid of the process according to the invention. The invention also relates to the use the -Arifcgririds of the formula III as far as it is after the Process according to the invention has been prepared for the preparation of a dihalovinyl-cyclopropanecarboxylic acid, especially such an acid in cis form.

The invention is illustrated in more detail by the following examples.

example 1
25th

Preparation of trans- ^ t ^ -dimethylcyclopropane-i, 2-dicarboxylic acid

1.5 g of a mixture obtained by reacting the ylid:

C ₂ H ₅ O.CO.CH with mesity oxide:

(CH ₃ ) ₂ C = CH - CO - CH ₃

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a f

1A-55 414 - y ^ - ₄ ς, 3 H 71 O

in toluene, and which contained 65% by weight of trans-2-acetyl-3,3-dimethylcyclopropanecarboxylic acid ethyl ester (5.3 mmol), was dissolved in 3 ml of ethanol and cooled in an ice-water bath. A solution of 0.5 g (12.5 mmol) of sodium hydroxide in 7 ml of water and 21 g of a cold aqueous solution of sodium hypochlorite containing 1.55 mmol of hypochlorite per gram was then added dropwise with stirring. The mixture was stirred for a further hour and the temperature was then slowly increased to 60 ^° C. and held at this value for one hour. The mixture was then cooled _/ extracted with dichloromethane, acidified to pH 1 with concentrated hydrochloric acid, saturated with sodium chloride and extracted with diethyl ether. The combined ether extracts were washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue contained 0.60 g of trans -3 »3-dimethylcyclopropane-1,2-dicarboxylic acid, corresponding to a yield of 72%.

Example 2

The procedure described in Example 1 was repeated with the following changes: Sodium hydroxide solution was not added, but instead 7 ml of water and heated to 60 ° C for 2 hours instead of 1 hour.

0.62 g of trans-3,3-dimethylcyclopropane-1,2-dicarboxylic acid were obtained, corresponding to a yield of 74 %.

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Example 3

Preparation of the anhydride of cis ~ 3,5-dimethylcyclopropane-1,2-dicarboxylic acid

1.2 g (7.6 mmol) of trans-3 »3-dimethylcyclopropane-1,2-dicarboxylic acid, which had been obtained according to Example 1, were mixed with 3» 5 g (45 mmol) of acetyl chloride at room temperature. After the mixture obtained had boiled for 2 hours with stirring, excess acetyl chloride was distilled off under reduced pressure (26.6 mbar). 4 ml of N-methylpyrrolidone were added to the residue and the mixture obtained was heated to 200 ° C. for 30 minutes with stirring in a nitrogen atmosphere and this temperature was maintained for 1 hour. After cooling to room temperature, most of the solvent was distilled off under reduced pressure (1.33 mbar) in a spinning band column. The residue ^L - contained 0.95 g of the anhydride of cis-3,3-dimethylcyclopropane-1,2-dicarboxylic acid.

Example 4

Preparation of the anhydride of cis ^^ - dimethylcyclopropane-1,2-dicarboxylic acid

1.5 g of trans-3 '3-dimethylcyclopropane-1,2-dicarboxylic acid, which had been obtained according to Example 1 were dissolved in 4 ml of acetyl chloride at 60 ⁰ C. After heating to 60 ^° C. for a further 1 hour, the volatile constituents were evaporated off under reduced pressure. The residue was dissolved in toluene to give 10 ml of the solution. This solution was passed through a glass tube filled with small pieces of glass with a

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Temperature of 300 ° C pumped (3.2 ml / h). A nitrogen flow was maintained through the tube during the experiment. The product stream was condensed. It was found that it contained the anhydride of cis-S ^ -dimethylcyclopropane-1,2-dicarboxylic acid as the main product. Yield 25 %.

Example 5

Preparation of anhydride of cis-3t3 ~ dimethylcyclopropane-1 _t 2-dicarboxylic acid

3 glass ampoules, each containing 40 ml of trans-3,3-dimethylcyclopropane-1,2-dicarboxylic acid and 0.15 g of acetic anhydride were placed in a 220 ° C oil bath given. The ampoules were then removed from the oil bath after 1/2, 1 or 2 hours.

The NMR spectrum of the contents showed that all three Ampoules the anhydride of cis-3,3-dimethylcyclopropane-1,2-dicarboxylic acid contained as the only cyclopropane derivative and that no decomposition products were formed.

Claims (10)

Claims Λ J Process for the preparation of cyclopropane derivatives of the general formula 1 ρ
in which R and R each independently represent a hydrogen atom or an alkyl group with up to 1 2 to 1.0 carbon atoms or R and R together are an alkylene group with 2 to 5 carbon atoms mean, or an alkali or alkaline earth metal salt thereof, characterized in, that you have an ester of the general formula 20th (II) 1 2
in which R and R have the meaning given above have, and R ^ an ₍ optionally substituted ^ / 2 1Α-55 414 - 2 - Alkyl group means with the hypochlorite or hypobromite of an alkali or alkaline earth metal in the presence of water. 2. The method according to claim 1, characterized in - g e k e η η - 1 2 shows that R and R are each an alkyl mean a group with 1 to 4 carbon atoms. 3. The method according to claim 2, characterized in that g e k e η η - 1 2 indicates that R and R each represent a methyl group mean. 4. The method according to claim 1 to 3, characterized in that R is an unsubstituted Denotes an alkyl group with up to 6 carbon atoms. j 5. The method according to claim 1 to 4, characterized in that g e - indicates that the hypochlorite or • 'Hypobromite is formed in situ. \ 20 * 6. The method according to claim 1 to 5, characterized. g e - j indicates that one is sodium hypochlorite ; used. '. 25th 7. The method according to claim 1 to 6, characterized in that - , indicates that at a temperature _: temperature in the range of -10 to 80 ° C works. 8. The method according to claim 1 to 7 »characterized g e indicates that the molar ratio of Hypochlorite or hypobromite to the compound of the general formula II is in the range from 3: 1 to 7: 1. / 3 1Α-55 414 "" '- 3 - 9. The method according to claim 1 to 8, characterized in that additionally the resulting compound into an anhydride of the general formula (III) 1 p
in which R and R have the meaning given above. 10. Use of the anhydride of the formula III for the preparation of cis-dihalovinylcyclopropanecarboxylic acid the formula Hal ₂ C = C CO ₂ H 1 2
and R in which R and R have the meaning given above. 6224