CS207797B2 - Method of making the derivatives of the clorstyrylpropan carboxyl acid - Google Patents

Abstract

1. Process for the preparation of chlorostyryl-cyclopropane-carboxylic acid derivatives of the formula I see diagramm : EP0006205,P12,F1 in which R represents alkyl or halogen and n represents 0 to 5 and R**1 represents hydrogen or alkyl, by reacting alpha-chlorobenzyl-phosphonic acid esters of the formula II see diagramm : EP0006205,P12,F2 in which R and n have the meaning indicated above and R**2 represents alkyl or phenyl or the two radicals R**2 together represent straight-chain or branched alkanediyl, with formyl-cyclopropane-carboxylic acid derivatives of the formula III see diagramm : EP0006205,P12,F3 in which R**1 has the meaning indicated above, if appropriate in the presence of diluents, at temperatures between -70 degrees C and +150 degrees C, characterised in that the reaction is carried out in the presence of alkali metal alcoholates or alkali metal hydroxides.

Description

(54) A method for producing chlorstyrylcyclopropanecarboxylic acid derivatives

The present invention relates to a novel process for the preparation of partially known chlorstyrylcyclopropanecarboxylic acid derivatives. These compounds can be used as intermediates for the production of insecticides.

It is already known that chlorstyrylcyclopropanecarboxylic acid esters, for example 3- (2-chloro-2-phenylvinyl) -2,2-dimethylcyclopropane-1-carboxylic acid ethyl ester, are obtained when phenylmethyl methanephosphonic acid diethyl ester is reacted with butyllithium. and then carbon tetrachloride and 3-formyl-2,2-dimethylcyclopropane-1-carboxylic acid ethyl ester (cf. DOS No. 2,738,150) are added sequentially.

However, this process has a number of disadvantages. The reaction is carried out at -70 ° C and thus requires expensive cooling. As a base, expensive butyllithium and a solvent which is inert to butyllithium are required, which must be carefully dried. The processing is time consuming and involves multiple extractions and distillations of solvents as well as a chromatographic separation process. Finally, the products are obtained in the form of a mixture of isomers in insufficient yields.

Thus, there is considerable interest in a process that is as completely free from these drawbacks as possible and that provides the desired products in good yields and with a high degree of purity.

Further, it is known that chlorostrylderivatives are obtained by reacting a N-chlorobenzylphosphonic acid ester with aldehydes in the presence of a base. Chimia 28 (1974), 656-657, J. Am. Chem. Soc. 87 (1965), 2777-2778).

The base used for this purpose in the prior art is sodium hydride, which is an expensive and difficult to obtain agent. The use of this synthesis method has so far been limited to a few examples.

It has now been found that the chlorstyrylcyclopropanecarboxylic acid derivatives of formula I,

in which it means

R is C 1 -C 4 alkyl or halogen, n is 0 to 5,

R @ ¹ hydrogen or C1 -C4 alkyl are obtained in good yields and in a high degree of purity by reacting the .alpha.-chlorobenzylphosphonic acid esters with aldehydes in the presence of bases if the .alpha.-chlorobenzylphosphonic acid esters of the formula II are reacted according to the invention;

(ll) in which

Wounds have the meanings given above and

R ² represents a C 1 -C 2 alkyl or phenyl group or both R ² together represent a straight or branched alkanediyl radical of up to 6 carbon atoms with the formylcyclopropanecarboxylic acid derivatives of the general formula III, in which:

R ¹ has the abovementioned meaning, in the presence of bases and in the presence of diluents at temperatures from -70 to - | -150 ° C.

Surprisingly, the novel chlorstyrylcyclopropanecarboxylic acid derivatives according to the invention can be obtained in better yields according to the new process, which is considerably more cost effective and easier to carry out than the known processes.

Further advantages of the process according to the invention are, for example, the possibility of carrying out the reaction at room temperature and the use of water-containing reaction media, the possibility of using relatively cheap bases instead of butyllithium or sodium hydride, relatively simple processing and good yields.

If, for example, diethyl α-chloro-4-fluorobenzylphosphonic acid and 3-formyl-2,2-dimethylcyclopropane-1-carboxylic acid methyl ester are used as starting materials and potassium hydroxide as an auxiliary base, the reaction according to the invention can be illustrated by this reaction scheme. :

OHC co-or ¹

(II

OHC CO-OCH.

4- кон o -KO-PIOC ^

- HjO

The process according to the invention advantageously produces the γ-α1-α-γ-α-γ-γ-γ-γ-α-γ-γ-α-γ-γ-β-γ-carboxylic acid derivative of the general formula I.

R is a straight or branched alkyl group having 1 to 4 carbon atoms, in particular a methyl group, or fluorine, chlorine or bromine, n number 0 to 2,

R @ ^{1 is} hydrogen, a straight or branched alkyl group having 1 to 4, in particular 1 or 2, carbon atoms.

The α-chlorobenzylphosphonic acid esters used as starting materials are defined by formula II.

In this general formula, the symbols obtained have the following preferred meanings:

R is a straight or branched (C 1 -C 4) alkyl group, in particular a methyl group, or fluorine, chlorine or bromine, n is an integer of 0 to 2,

R ² represents methyl, ethyl, phenyl or both radicals R ² together represent a 2,2-dimethyl-1,3-propanediyl radical.

Examples of such compounds are:

α-chlorobenzylphosphonic acid dimethyl ester and diphenyl ester, α-chloro-4-methylbenzylphosphonic acid, α-chloro-4-fluorobenzylphosphonic acid, α-chloro-4-chlorobenzylphosphonic acid, α-chloro-3,4-dichlorobenzylphosphonic acid, and 1-chloro-3-bromobenzylphosphonic acid and α-chloro-4-bromobenzylphosphonic acid.

The .alpha.-chlorobenzylphosphonic acid esters of formula (II) are partially known. These compounds can be prepared by reacting the α-hydroxybenzylphosphonic acid esters of formula IV,

(IV) in which:

R 1 and R ² are as defined above, with a chlorinating agent, for example thionyl chloride or phosphorus oxychloride, at temperatures of 0 to 100 ° C, preferably at 20 to 80 ° C [cf. Chimia 28 (1974), 656-657, J. Am. Chorn. Soc. 87 (1965), 2777-2778.

The α-hydroxybenzylphosphonic acid esters used to prepare the starting materials of formula II are defined by formula IV. In this formula, the general symbols have the following preferred meanings:

R, n, R 2 are radicals which have already been mentioned as being useful in the definition of the radicals in formula II.

Examples are:

α-hydroxybenzylphosphonic acid dimethyl, diethyl and diphenyl ester, α-hydroxy-4-methylbenzylphosphonic acid, α-hydroxy-4-fluorobenzylphosphonic acid, α-hydroxy-4-chlorobenzylphosphonic acid, α-hydroxy-3,4-dichlorobenzylphosphonic acid, and- hydroxy-3-bromobenzylphosphonic acid; and α-hydroxy-4-bromobenzylphosphonic acid.

The α-hydroxybenzylphosphonic acid esters of formula IV are partially known. These compounds are obtained according to known procedures, generally by reaction of the aldehydes of formula V,

(V) in which

Ran is as defined above, with phosphorous acid esters of formula VI,

O OR2 • W / Η — P \ OR ² [VI) in which

R 2 is as defined above, optionally in the presence of a catalyst, for example triethylamine, at temperatures of 0 to 150 ° C, preferably 30 to 100 ° C [cf. Houbon-Weyl, Methoden der organischen Chemie, 4th edition (1963), vol. 12/1, pp. 475-483, Georg Thieme Verlag, Stuttgart].

Examples of aldehydes of formula V include:

benzaldehyde,

4-methylbenzaldehyde,

4-fluorobenzaldehyde,

4-chlorobenzaldehyde, d, 4-dichlorobenzaldehyde,

3-bromobenzaldehyde a

4-bromobenzaldehyde.

The aldehydes of formula V are known compounds.

Examples of phosphorous acid esters of formula VI include:

phosphorous acid dimethyl ester (dimethylphosphite), phosphorous acid diethyl ester (diethylphosphite), phosphorous acid diphenyl ester (diphonylphosphite).

The phosphorous acid esters of formula (VI) are also known compounds.

The formylcyclopropanecarboxylic acid derivatives which are further used as starting materials are defined by formula III. Preferably, the general symbols in this formula have the following meanings:

R ¹ represents a straight or branched alkyl group having 1 to 4 carbon atoms, in particular 1 or 2 carbon atoms.

Examples of compounds of formula III are: 2,2-dimethyl-3-formylcyclopropane-1-carboxylic acid methyl ester and ethyl ester.

The compounds of formula III are known or can be prepared according to known processes, generally by reacting known 1-alkenyl cyclopropanecarboxylic acid esters with ozone [cf. U.S. Patent No. 3,679,667, DOS No. 2,621,433, and French Patent No. 2,281,918).

The process for preparing the compounds of the formula I according to the invention is generally carried out using diluents. Virtually all inert organic solvents are suitable as diluents. These include, in particular, aliphatic and aromatic or chlorinated hydrocarbons, such as gasoline, benzene, toluene, xylene, methylene chloride, chloroform, carbon tetrachloride, chlorobenzene and o-dichlorobenzene, ethers such as diethyl ether and dibutyl ether, tetrahydrofuran and dioxane, alcohols such as methanol, ethanol , n-propanol and isopropyl alcohol, n-butanol, isobutanol, sec-butanol and tert-butanol, as well as dimethyl sulfoxide.

When working in a two-phase environment, in addition to a 50% aqueous solution of sodium hydroxide with water, virtually immiscible solvents such as gasoline, benzene or toluene are used.

As bases, bases customary in olefins can be used. Alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal alkoxides such as methoxide, ethoxide, n-propoxide, isopropoxide, n-butoxide, isobutoxide, sodium and potassium sec-butoxide and tert-butoxide, e.g. sodium hydride as well as lithium compounds with alkyl residues such as butyllithium.

Sodium hydroxide and potassium hydroxide as well as sodium methoxide and sodium ethoxide are preferably used as bases.

Reaction temperatures are generally in the range of -70 to +150 ° C, preferably -10 to +50 ° C. Celsius. The reaction is generally carried out at atmospheric pressure.

In order to carry out the process according to the invention, the individual components are usually used in equimolar amounts. Only bases are usually used in greater excess: when operating in a single-phase system up to 30 mol%, preferably up to 15 mol%; using a 50% sodium hydroxide solution as the second phase generally in 5- to 15-fold the stoichiometrically required amount.

The alkoxides are optionally produced in situ from alcohols and alkali metals.

Generally, the base and optionally the catalyst are present in one or more of the aforementioned diluents. The reactants, i.e., the .alpha.-chlorobenzylphosphonic acid ester and the formylcyclopropanecarboxylic acid derivative, are then added, optionally dissolved in one of the abovementioned solvents, respectively. To complete the reaction, the reaction mixture is kept under stirring at the indicated temperature range for several hours.

For working up, water is added to the reaction mixture, the reaction mixture is optionally acidified with hydrochloric acid and extracted with methylene chloride. The organic phase is dried and the solvent is distilled off in vacuo. The product obtained after distilling off the solvent is optionally purified by vacuum distillation or, if it is not distillable without decomposition, by so-called "distillation", i.e. by prolonged heating under reduced pressure to slightly elevated temperatures. Boiling point or refractive index is used for characterization.

Compounds of formula I in which R 1 and R ¹ are as defined above are known (cf. DOS No. 2,738,150).

Such compounds can be used as intermediates for the preparation of insecticidally active compounds of formula Ia,

The compounds of formula (Ia) can be prepared from the corresponding intermediates of formula (I) in a manner known per se, for example by saponifying the alkyl ester of chlorstyrylcyclopropanecarboxylic acid of formula (I) at 20 to 100 ° C followed by acidification with hydrochloric acid to the corresponding chlorstyrylcyclopropanecar

R and n are as defined above,

R ³ represents hydrogen, cyano or ethynyl,

R ⁴ and R ⁵ , which may be the same or different from each other, represent hydrogen or halogen (cf. DOS No. 2,738,150).

boxylic acids from which carboxylic acid chlorides are prepared by reaction with thionyl chloride in benzene at temperatures of 20 to 100 ° C, and these are reacted with phenoxybenzyl alcohols of the general formula VII,

in which

R ^3, R ⁴ and R ⁵ have the meaning given above, optionally in the presence of an acid binding agent, for example pyridine, and optionally in the presence of a diluent, such as benzene.

The use of products which can be produced in this way as insecticides is known (cf. DOS No. 2,738,150).

The process according to the invention is illustrated in more detail by the examples.

Example 1

=с = ся, со-ос _л н ₅

W ₅ c CH 3

2.53 g (0.11 mol) of sodium are dissolved in 50 ml of ethanol by successive addition of sodium. When all the sodium has dissolved, 150 ml of anhydrous tetrahydrofuran is added and 29.7 g (0.1 mol) of diethyl 4-chloro-chlorobenzylphosphonic acid diethyl ether dissolved in 30 ml of anhydrous tetrahydrofuran are added dropwise at 0 ° C with stirring. . The reaction mixture is stirred for a further 2 hours at 0-5 [deg.] C. and then 17 g (0.1 mol) of cis / trans-2,2-dimethyl-3-formylcyclopropanecarboxylic acid ethyl ester, which is dissolved in 30 ml of anhydrous tetrahydrofuran, is added dropwise. , with stirring at 0 ° C. The reaction mixture was then stirred at 20-25 ° C for 12 hours. The reaction mixture is exemplified by the formula

C.

500 ml of water are added thereto, and the mixture is extracted twice with 300 ml of methylene chloride each time. The organic phase is separated, dried over magnesium sulphate, the solvent is distilled off under a water pump vacuum and the residue is distilled under vacuum. 23.2 g (74.1 of theory) of 2,2-dimethyl-3- (2-chloro-2- (4-chlorophenyl) -vinyl) cyclopropanecarboxylic acid ethyl ester (mixture of cis, trans and E, Z isomers) are obtained. in the form of a yellow oil with a boiling point of 150 to 165 ° C / 133 Pa.

Example 2

H ₃ c CH,

29.7 g (0.1 mol) of 4-chloro-α-chlorobenzylfoisphonic acid diethyl ester is dissolved in 150 ml of tetrahydrofuran and a solution of 6.2 g (0.11 mol) of hydroxide is added dropwise with stirring at 0 ° C. of potassium in 60 ml of methanol. The reaction mixture is stirred for a further 2 hours at 0-5 ° C and then 17 g (0.1 mol) of cis / trans-2,2-dimethyl-3-formylcyclopropanecarboxylic acid ethyl ester is added dropwise with stirring at 0 ° C, which is dissolved in 30 ml of anhydrous tetrahydrofuran. The reaction mixture was then stirred at 20-25 ° C for 12 hours. Water (500 ml) was then added to the reaction mixture and the mixture was extracted twice with methylene chloride (300 ml). The organic phase is separated, dried over magnesium sulphate, the solvent is distilled off under a water pump vacuum and the residue is distilled under vacuum. 17 g of a mixture of 2,2-dimethyl-3- (2-chloro-2- (4-chlorophenyl) vinyl) cyclopropanecarboxylic acid ethyl ester and methyl ester (mixture of cis / trans, E and Z isomers) are obtained in the form of a yellow oil, which boils in the temperature range of 145 to 165 ° C / / 133 Pa.

The following compounds can be prepared in an analogous manner to that described in Example 1 or 2:

Yield Refractive index (% of theory) Boiling point

68.2

140-142 ° C / 267 Pa

СО'ОС _Х Н _У

Boiling point index

Example δ.

Formula

Yield (% of theory)

58.7 135-140 ° C / 267 Pa n _D ²⁵ : 1.5621

To a mixture of 100 ml of toluene, 100 ml of 50% aqueous sodium hydroxide solution and 2 g of tetrabutylammonium bromide, 17 g (0.1 mol) of cis-trans-3- ethyl ester are slowly added dropwise with stirring at 20 to 35 ° C (ice-cooling). forinyl-2,2-dimethylcyclopropanecarboxylic acid and 29.7 g (0.1 mol) of N-chloro-4-chlorobenzylphosphonic acid diethyl ester dissolved in 20 ml of toluene. The reaction mixture is then stirred for 12 hours at room temperature, then poured into 600 ml of water, the toluene phase is separated, the aqueous phase is acidified with concentrated hydrogen chloride and then extracted twice with 200 ml of methylene chloride each time.

The methylene chloride phase was separated, dried over magnesium sulfate, and then the solvent was distilled off in a water pump vacuum. The residual oily yellow residue was distilled. 15.2 g (53.3% of theory) of 3- [2-chloro-2- (4-chlorophenyl) -vinyl] -2,2-dimethylcyclopropanecarboxylic acid are obtained in the form of a viscous resin having a boiling point of 190 to 195 ° C. Celsius / 133 Pa.

Example 7

22.2 g (0.071 mol) of 2,2-dimethyl-3- [2-chloro-2- (4-chlorophenyl) vinyl] cyclopropanecarboxylic acid ethyl ester is dissolved in 100 ml of ethanol and solution 5 is then added to this solution. 7 g of sodium hydroxide in 100 ml of water and the mixture was heated under reflux for 4 hours. The ethanol is then distilled off under a water pump vacuum, the residue is taken up in 300 ml of hot water and extracted once with 300 ml of methylene chloride. The aqueous phase is separated, acidified with concentrated hydrochloric acid and then extracted twice with 300 ml of methylene chloride each time. The organic phase is separated and dried over magnesium sulphate, after which the solvent is distilled off under a water pump vacuum. The last residual solvent was removed by brief distilling at 267 Pa and a bath temperature of 60 ° C. 15.5 g (76.6% of theory) of 2,2-dimethylcyclopropanecarboxylic acid (mixture of cis and trans isomers, E and Z) are obtained first in the form of a very viscous yellow oil which solidifies after a while to form a crystalline product and then melts ranging from 94 to 114 ^Q C.

The following compounds can be prepared in an analogous manner to that described in Example 7:

· Ί

Example #

Formula

Yield (% 'of theory)

68.3

H ₃ C CH,

62.6 g (0.2 mol) of 2,2-dimethyl-3- [2-chloro-2- (4-chlorophenyl) vinyl] cyclopropanecarboxylic acid ethyl ester (mixture of isomers) is dissolved in 100 ml of ethanol, then added solution of 10 g of sodium hydroxide in 100 ml of water and the reaction mixture is heated under reflux for 6 hours. The ethanol is then distilled off under a water pump vacuum and 150 ml of water are added to the residue. The reaction mixture was then cooled to 5-10 ° C for 12 hours. The precipitate formed is filtered off and dried. The solid is then suspended in 60 ml of methylene chloride and 30 ml of concentrated hydrochloric acid is added. The organic phase is separated, dried over magnesium sulphate and the solvent is evaporated off under a water pump vacuum. 3.6 g (6.3% of theory) of cis-2,2-dimethyl-3- [2-chloro- (4-chlorophenyl) -vinyl] -cyclopropanecarboxylic acid having the cis-configuration of the phenyl and cyclopropane residues on the double bond are obtained. colorless rats

m.p. 140 DEG-142 DEG C. (from ethanol). This configuration is confirmed by the H ¹ -NMR- and C ¹³ -NMR spectra.

The α-chlorobenzylphosphonic acid esters of formula II used as starting materials can be prepared as follows:

Example 1a

CH-PIOC4Ct

A mixture of 20.2 g (0.0725 mol) of 4-chloro-α-hydroxybenzylphosphonic acid diethyl ester, 65 g of dichloromethane and 5.8 g (0.0725 mol) of pyridine is mixed at 20 to 40 ° C with slight water cooling during about 1 hour with the addition of 9.2 g (0.0768 mol) of thionyl chloride. The reaction mixture was then heated at reflux for 3 hours and stirred for 12 hours without further heating. The reaction mixture is poured onto about 100 g of ice-water, the organic phase is separated and dried. After distilling off the solvent, the residue is concentrated at 800 Pa and 45 ° C. 21 g (97.7 why theory) of 4-chloro-.alpha.-chlorbenzylfosfonové acid as a viscous yellow oil having a purity of 98.6% (gas chromatogram) and a refractive index n _D ²⁴ - 1.5250.

The following compounds are obtained in an analogous manner:

Example # Yield (% of theory) Refractive index 2a © -ch-pioc ^ Cl 93.7 n _D 23 ₌ 1.5Ц7 3a 0 F- ^ ~ -CH-lp (ОС _к Н ₅ ) ^ Cl

Example #

Yield Refractive index (° / o theory)

4a

O

5a ct

ct,

The N -hydroxybenzylphosphonic acid esters of formula IV required as intermediates for the preparation of these starting materials can be prepared as follows:

Example 1 a d lb

OC 1 CH 2 (OC ₂ H ₅ ) ₂

OH

To a mixture of 20.7 g (0.15 mol) of diethylphosphite and 1.09 g (0.0109 mol) of triethylamine was as described in Example 1.

21 g (0.150 mol) of p-chlorobenzaldehyde are introduced at 50 DEG-70 DEG C. over 1 hour under cooling with water. The reaction mixture was then further stirred at 70 ° C for 1 hour. After cooling, the mixture is taken up in 40 g of toluene and the toluene solution is washed several times with dilute hydrochloric acid and cold water. The organic layer was separated and the solvent was removed in vacuo. The solid residue melts at 70-72 ° C. Yield: 37 g (88.5% of theory) of 4-chloro-.alpha.-hydroxybenzylphosphonic acid diethyl ester.

The following compounds can be prepared in an analogous manner:

Yield (% · theory) Melting point (° C)

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of chlorstyrylcyclopropanecarboxylic acid derivatives of the general formula (I) in which: R is C 1 -C 4 alkyl or halogen, n is 0 to 5 a R @ ^{1 is} hydrogen or C1 -C4 alkyl, by reacting .alpha.-chlorobenzylphosphonic acid esters with aldehydes in the presence of a base, characterized in that it is converted to the .alpha.-chlorobenzylphosphonic acid ester of the formula II in which: R a is as defined above and, R ² represents a C 1 -C 2 alkyl or phenyl group, or both R ² together represent a straight or branched alkanediyl group of up to 6 carbon atoms, acting as formylcyclopropanecarboxylic acid derivatives of formula III, OHC COOR ¹ У in which R ¹ has the abovementioned meaning, in the presence of bases and solvents at temperatures of -70 to +150 ° C.