CS209817B2 - Method of making the new cyklopropancarboxyl acids,event. the reactive derivatives thereof - Google Patents

Description

The invention relates to a process for the preparation of novel cyclopropanecarboxylic acids or their reactive derivatives of the general formula II

in which

R ¹ is fluorine or trifluoromethyl,

R ³ is fluoro, chloro or bromo or is the radical R ¹ -CF 2 a

Z ¹ is halogen, preferably chloro or hydroxy.

These compounds of the formula II can be used as starting materials for the preparation of inhaled and aharicidally active esters of fluralkenyl-substituted cyclopropanecarboxylic acids of the formula I

in which

R ¹ is fluorine or trifluoromethyl,

R ³ represents fluorine, chlorine, bromine or the radical R ¹ CF2a

R ² represents a group of formula

or (V),

where

R ¹¹ is hydrogen or cyano,

R ⁹ is hydrogen or halogen, especially fluoro, and

R ¹⁰ is optionally substituted by one or more halogen, methyl, or methoxy substituted aryl, especially phenyl.

The novel cyclopropanecarboxylic acids or their reactive derivatives of the general formula (II) according to the invention are prepared by the preparation of compounds of the general formula (IV)

(IV) in which:

R represents a —COO-alkyl group wherein the alkyl contains 1 to 4 carbon atoms, a cyano group or —COCH3 group and

R ¹ and R ³ are as defined above when R is -COO-alkyl wherein the alkyl contains 1 to 4 carbon atoms or cyano, saponified, or when R is -COCH 3, oxidized and optionally an acid in which R is —COOH is reacted with a halogenating agent.

Novel compounds of formula IV

R ³ Hal CHs CH3 ₁ II

R ¹ -CF C-CH2-CH-C-CH 2 R

Hal in which

R ¹ , R ³ and R 2 are as defined above, and Hal represents chlorine or bromine, dehydrohalogenates.

New compounds of formula VR ³ Hal CH 3 ^{1 11}

R1CF2 — C — CH2 — CH — C — CH2R (V),

Hal CHs in which

R, R ¹ , R ³ and Hal have the meanings given above, obtained by halogenating derivatives of the general formula VI

R ³

AND

R ¹ —CF ² C (Hal) 2 (VI) wherein

R ¹ is fluorine or trifluoromethyl, and

Hal may be the same or different from each other and is chlorine or bromine and

R ³ , as defined above, adds to the olefins of formula VTI

in which

R is as defined above, optionally in the presence of a catalyst.

Acid chlorides are preferably used as relative derivatives of the compounds of formula II.

Examples of compounds of formula II are:

in which

R ¹ and R ³ are as defined above, and R is cyano, -COCH 3, or -COO-alkyl, wherein the alkyl contains 1 to 4 carbon atoms, is obtained by providing compounds of formula V

2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid and its chloride,

2,2-dimethyl-3- (2'-bromo-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid and its chloride,

2,2-dimethyl-3- (2'-chloro-3 ', 3', 4 ', 4', 4 ', pentafluorobutenyl) cyclopropanecarboxylic acid and its chloride,

2,2-dimethyl-3- (2'-bromo-3 ', 3', 4 ', 4'-pentafluorobutenyl) cyclopropanecarboxylic acid and its chloride,

2,2-dimethyl-3- (2'-fluoro-3 ', 3', 3'-trifluoropropenyl cyclopropanecarboxylic acid and its chloride,

2,2-Dimethyl-3- (2'-trifluoromethyl-3 ', 3', 3 ', trifluoropropenyl cyclopropanecarboxylic acid and its chloride.

The novel acids or acid halides of the formula (II) are prepared from the compounds of the formula (IV) as described above.

In variant a), when R represents a -COO-alkyl group in which the alkyl contains 1 to 4 carbon atoms, the saponification is carried out in a customary manner under acidic or alkaline conditions. The saponification under alkaline conditions is preferred.

When R is cyano, this nitrile is converted to an ester group by dissolving the nitrile in an appropriate alcohol of formula alkyl-OH wherein the alkyl contains 1 to 4 carbon atoms and the solution is saturated with hydrogen chloride, usually at about 0 to 20 ° C. After a period of standing, the imide chloride forms from which the ester is formed by the action of water.

Suitable saponification agents are all customary saponification agents, such as sulfuric acid, acetic acid or alkali metal hydroxides. Particularly preferred is potassium hydroxide in an alcoholic solution, for example methanol.

The saponification can be carried out at an elevated temperature, for example at a temperature between 20 and 100 ° C, but preferably at 20 to 40 ° C.

The acids are liberated by acidification with aqueous acid solutions and separated from the salts by extraction, and optionally purified by distillation.

The acid halides may be prepared by conventional methods using conventional halogenating agents such as SOCl 2, COCl 2, PCb, PCb, oxalyl chloride or oxalyl bromide, phosphorus tribromide.

In process variant b), R is -COCH 3. The acid is obtained by oxidation, preferably by treatment with hypochlorite or hypobromite. Examples of such agents include sodium hypochlorite, potassium hypochlorite, potassium hypochlorite, calcium hypochlorite, sodium hypochlorite, potassium hypochlorite and calcium hypochlorite. Furthermore, the reaction can also be carried out by introducing the halogen into an aqueous alkali metal hydroxide solution containing the starting material. The reaction temperature is generally -20 to 100 ° C, preferably 0 to 70 ° C. In general, water is used as the solvent, but organic solvents may also be added as co-solvents. By adding a phase transfer catalyst such as quaternary ammonium salts, the reaction can be accelerated. Suitable quaternary ammonium salts are the quaternary ammonium salts mentioned above.

Examples of novel compounds of formula (IV) are:

2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid methyl ester, 2,2-dimethyl-3- (2'-chloro-3 ', 3', ethyl ester, 3'-Trifluoropropenyl) cyclopropanecarboxylic acid, 2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid butyl ester, 2,2-dimethyl-3- (2-methyl ester) 1-cyano-2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropane, 1'-bromo-3 ', 3', 3'-trifluoropropenyl i-cyclopropanecarboxylic acid; -cyano-2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropane, 1-acetyl-2,2-dimethyl-3- (2'-chloro-3) 3 ', 3', 3'-trifluoropropenyl) cyclopropane, 2,2-dimethyl-3- (2'-trifluoromethyl-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid ethyl ester.

The novel compounds of formula (IV) may be prepared by the process described from compounds of formula (V) by dehydrohalogenation. This reaction can be illustrated by the following reaction scheme:.

1'-CF, -C (Hill-CH-CH (Hill-C-CH, -R

R ^{3 CH} 2>

H ^ C h: ', · <·

->

-2 HHaI

->r'-cf ₂ -c = ^ \

The dehydrohalogenation is carried out by treatment with bases in the presence of diluents. Suitable bases are: sodium hydroxide, potassium hydroxide, potassium carbonate, alkoxides, such as sodium methoxide, sodium isopropoxide or potassium tert-butoxide.

Suitable solvents are, in particular, alcohols, such as methanol, ethanol, n- or isopropanol, butanol, tert-butanol, glycol or glycol monomethyl ether. Further, optionally chlorinated hydrocarbons or ethers such as benzene, toluene, xylene, chlorobenzene, dichlorobenzene, methylene chloride, tetrahydrofuran, dioxane, dimethoxyethane. It is also possible, especially when using sodium hydroxide or potassium hydroxide, to work in a two-phase system, such as in a mixture of toluene and water. Optionally, a phase transfer catalyst such as a quaternary ammonium salt may be added. This measure not only makes sense when working in a two-phase system, but also when working in an anhydrous environment, for example, if potassium carbonate is used as the base.

A similar reaction is described in DOS No. 2,539,896. Although the preferred temperature range is 60-100 [deg.] C. when using sodium methoxide or sodium ethoxide, very little of the product of formula (IV) is obtained under these conditions. mol of hydrogen halide to give the product of formula VIII

+ R ¹ CF _Z C (H _and 1 ->

?

R ¹ CF _z C (HaD CH _z CH (H & O-C-CH ₂ r / \

H, C CH, wherein R and R ¹ are as defined above.

Surprisingly, it has now been found that virtually no product of formula VIII is formed when a base, preferably sodium methoxide or sodium ethoxide, is introduced in a solvent, then a compound of formula V is slowly added to be dehydrohalogenated, initially at about ΰ to 30 ° C and then to complete the reaction at 20 to 60 ° C, preferably at 35 to 50 ° C. It is particularly surprising that the dehydrohalogenation takes place even at these lower temperatures.

Examples of compounds of formula V are:

3,3-dimethyl-4,6,6-trichloro-7,7,7-trifluorenantic acid methyl ester, 3,3-dimethyl-4,6,6-trichloro-7,7,7-trifluorenantic acid ethyl ester, hutyl ester 3 3,3-dimethyl-4,6,6-trichloro-7,7,7-trifluorenantic acid, 3,3-dimethyl-4,6,6-trichloro-7,7-trifluorenantic acid nitrile, 3,3-dimethyl methyl ester -4,6,6-tribromo-7,7,7-trifluorenantic acid,

2,2-dimethyl-3,5,5-trichloro-6,6,6-trifluorohexylmethyl ketone, 3,3-dimethyl-4,6-dichloro-6-trifluoromethyl-7,7,7-trifluorenantanoic acid ethyl ester.

The novel compounds of formula (V) are obtained from compounds of formulas (VI) and (VII) as described above. Compounds of formulas VI and VII are known.

This process can be illustrated by the following reaction scheme:

For example, if 3,3-dimethyl-4-pentenoic acid-1,1,1-trifluoroethane methyl ester is used as the starting material, the reaction scheme may be illustrated as follows:

/ Í ₃ C ca ^Cf 3 ^CCl 3 ^{f Z} CKCOOCH .->

3 3> C ^ CCClICHjCHCl-C- ^CO COC ^

H ₃ C ^x CH ₃

By way of example, the following starting materials of formula VI are:

1,1.1-trichloro-2,2,2-trifluoroethane,

1,1.1-tribromo-2,2,2-trifluoroethane, 1-chloro-1,1-dibromo-2,2,2-trifluoroethane,

1,1-dichloro-1-bromo-2,2,2-trifluoroethane,

1.1.1- trichloro-2,2,3,3,3-pentafluoropropane,

1,1.1-tribromo-2,2,3,3,3-pentafluoropropane,

1.1.1-tetrafluoro-2,2-dichloroethane,

1.1.1.3.3.3- hexafluoro-2,2-dichloropropane,

1.1.1.2- tetrafluoro-2,2-dibromoethane,

1.1.1.3.3.3-hexafluoro-2,2-dibromopropane.

Examples of starting materials of formula (VII) are:

3,3-dimethyl-4-pentenoic acid methyl ester, 3,3-dimethyl-4-pentenoic acid ethyl ester, 3,3-dimethyl-4-pentenoic acid butyl ester, 3,3-dimethyl-4-pentenoic acid nitrile,

2,2-dimethyl-3-butenylmethylketone.

This process is preferably carried out under pressure, but can also be carried out using high boiling compounds of the formula VI at atmospheric pressure.

The pressure range may vary within wide limits, but is about 0.1 to 3 MPa, preferably 0.3 to 1.5 MPa. The overpressure can be achieved by forcing an inert gas such as nitrogen into the reaction vessel.

The reaction temperature may be between 50 ° C and 200 ° C, but is preferably 100 ° C to 150 ° C. Optionally both starting materials are added in a diluent.

Suitable diluents are: aliphatic or aromatic hydrocarbons, such as gasoline or toluene, alcohols, such as methanol, ethanol, propanol, or tert-butanol, nitriles, such as acetonitrile or propionitrile and dimethylsulphide, alcohols and acetonitrile are preferred.

Catalysts are required to conduct the reaction:

as well as catalysts that provide free radicals such as azobisisobutyronitrile, benzyl peroxide or di-tert-butyl peroxide.

The compounds of formula (VI) are used in equimolar amounts, but preferably in excess.

bj catalyst mixtures consisting of a metal salt, an amine and optionally a small amount of benzoin. The metal salt may be present in the form of a hydrate, the amine may also be used in the form of a salt, for example the hydrochloride.

Examples of metal salts include: cuprous chloride, cuprous chloride, ferrous chloride, ferric chloride, copper sulfate, cobalt chloride, zinc chloride, ferrous sulfate, ferric acetate, copper or iron acetylacetonate.

Examples of amines include: dimethyl amine, diethylamine, trimethylamine, triethylamine, diisopropylamine, n-butylamine, benzylamine, ethanolamine, aniline, pyridine. Preferred amines are dimethylamine, diethylamine (such as hydrochlorides), as well as n-butylamine.

Preferably, at least 1.5 mol, preferably 2 to 10 mol, of organic amine per 1 mol of metal salt are used. The metal salt is used in an amount of from 0.01 to 15 mol%, preferably 0.05 to 10 mol%, based on the compounds of the general formula VII.

Often, the addition of an equimolar amount of benzoin based on the metal salt is preferred.

The following examples illustrate the invention but are not limited thereto:

He did

Preparation of compound of formula

g of trans-2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid is dissolved in 150 ml of methylene chloride, a few drops of dimethylformamide are added to the solution, and at room temperature, introducing phosgene until the reaction is complete (infrared control), then excess phosgene and methylene chloride are distilled off, and the remainder is distilled at 40-50 ° C / 66.7 Pa. 2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid m _D 20 = 1.4554.

g of cis-2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid is dissolved in 50 ml of thionyl chloride and the solution is heated to boiling for one hour. After excess thionyl chloride was distilled off, the residue was distilled under high vacuum. There is obtained cis-2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid chloride of bp 52-54 ° C / 120 Pa and η _η 2θ = 1.4520.

Example 3

In the same manner as described in Example 1 or 2, 2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid chloride is obtained from 2,2-dimethyl-3 - (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropacarboxylic acid using a mixture of stereoisomers containing all 4 possible stereoisomers.

Example 1 a d 4

Cl

To 18 g of trans-2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid ethyl ester was added 100 ml of 3N methanolic potassium hydroxide solution and the reaction mixture was stirred for 6 hours at room temperature. 300 ml of ice-water are then added and the pH is adjusted to 1 by addition of concentrated hydrochloric acid. Extraction with petroleum ether yields 11.2 g of carboxylic acid, m.p. 110-11 ° C.

Example 5

In analogy to Example 4, 9.4 g of the cis-carboxylic acid isomer is obtained from 15 g of cis-2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid ethyl ester. 90-91 ° C.

Example 6

In an analogous manner to that of Example 4, 2,2-dimethyl-3- (2 '-' Chloro-3 ', 3', 3'-trifluoropropenyl) cyclopropanecarboxylic acid ethyl ester (mixture of isomers) yields 2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-fluoropropenyl) -cyclopropanecarboxylic acid, which remains a liquid at room temperature, boiling point 90-93 ° C / 80 Pa.

Example 7

By distillation in a ring packed column, the compound of formula is isolated in the pure state from the mixture of isomers resulting from the preparation of 2,2-dimethyl-3- (2'-chloro-3 ', 3', 3'-trifluoromethyl) cyclopropanecarboxylic acid ethyl ester. :

OF

C boiling point: 103 ° C / 2133 Pa n _D 20 = 1.4366

boiling point: 102 ° C / 2133 Pa η _η 2θ - 1,4356 as well as the third isomer, presumably

boiling point: 105 ° C / 2133 Pa n _D ²⁰ : 1.4364

Example 8

Cl

To a solution of 20.7 g of sodium in 300 ml of ethanol, 135 g of 3,3-dimethyl-4,6,6-trichloro-7,7,7-trifluorenanthonic acid methyl ester was added dropwise over 3 hours with stirring at room temperature. The reaction mixture was further stirred at room temperature for 1 hour and then heated at 45 ° C for 7 hours. After cooling, the precipitated sodium chloride is filtered off, the filtrate is concentrated somewhat in vacuo, 500 ml of water are added and the mixture is brought to neutral pH. Extraction with methylene chloride and traction distillation gave 90 g of the ethyl ester

2,2-dimethyl-3- (2'-chloro-3 ', 3', 3 ', 3'-trifluoropropenyl) cyclopropanecarboxylic acid (mixture of isomers having a boiling point of 55-57 ° C / 1/2 mm Hg).

The methyl ester is obtained by treatment with sodium methoxide in methanol.

Example 9

CH3

AND.

F3C-CCl2-CH2-CHCl-C-CH2CO2CH3

CH3

37.5 g of 3,3-dimethyl-4-pentenoic acid methyl ester, 99.4 g, 1,1-trichloro-2,2,2-trifluoroethane, 22 g of acetonitrile, 325 mg of ferric chloride hexahydrate (FeCl3, 6 H2O) , 255 mg of benzoin and 200 mg of dimethylamine hydrochloride were heated in a 250 ml autoclave at 0.6 MPa nitrogen for 7 hours at 100 to 120 ° C and then the reaction mixture was distilled through a 50 cm high Vlgreux column to give 70 g of the methyl ester. 3,3-dimethyl-4,6,6-trichloro-7,7,7-trifluorenanthonic acid, b.p. 88-92 ° C / 20 Pa.

The following compounds are obtained in an analogous manner:

example compound boiling point (° C / Pa)

CHs

AND

FsC-CCl2-CH2-CHCl-C-CH2CO2C2H5

AND

CHs

CH3

AND

FsC-CCl2-CH2-CHCl-C-CH2COCH3

AND

CH3

CHs

AND

FsC — CCl2 — CH2 — CHCl — C — CH2CN

AND

CH3

CH3

AND

F3C-CCl-CH2-CHCl-C-CH2CO2CH3

CF3 CH3 to 102 / 26.7 Pa to 88 / 26.7 Pa

104 to 110 / 33.3 Pa to 83 / 26.7 Pa

Claims (1)

A process for the preparation of novel cyclopropanecarboric acids or their reactive derivatives of the general formula II in which: R ¹ is fluorine or trifluoromethyl, R ³ is fluoro, chloro or bromo or is the radical R ¹ CF ² -a Z ¹ is halogen, preferably chloro or hydroxy, characterized in that the compounds of formula IV are: R represents a —COO-alkyl group wherein the alkyl contains 1 to 4 carbon atoms, —CN or —COCH3 and R ¹ and R ³ are as defined above when R is -COO-alkyl wherein the alkyl contains 1 to 4 carbon atoms or cyano, saponified, or when R is -COOCH 3, oxidized and optionally the acid in which R is COOH is reacted with a halogenating agent.