CH629758A5 - Process for preparing cyano-substituted cyclopropane derivatives - Google Patents

Description

629758

2nd

PATENT CLAIMS 1. Process for the preparation of cyan-substituted cyclopropane derivatives of the general formula:

H CH = C (Hal),

IL

Rr

CN

'H

(II)

wherein shark is a fluorine, chlorine or bromine atom and Rj and R2 is an alkyl group having 1 to 4 carbon atoms, characterized in that a compound of the formula

R

ï

1 / CH-CH2-C (Hal) 2

R,

C.

CHCOOR,

(III)

I.

CN

The invention relates to the production of cyano-substituted cyclopropane derivatives which are suitable as intermediates for the production of insecticides, such as the 3-phenoxybenzyl ester of 2- (2,2-dichlorovinyl) -3,3-dimethylcyclo-propane carboxylic acid .

A lot of development work has gone into the synthesis of these cyclopropanecarboxylic acids (NL-OS 7 510 479 and 7 509 631). All known processes for the production of these acids are complicated and expensive and require multistage processes.

The invention now relates to the preparation of cyano-substituted cyclopropane derivatives of the general formula:

15

, CH = C (Hal) 2

(II))

wherein shark, fluorine, chlorine or bromine and R1 and R2 are alkyl groups with 1-4 C atoms, preferably 25 are the methyl group. According to the inventive method, a compound of the general formula wherein X and Y is a chlorine or bromine atom and R4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, is cyclized in the presence of a base and hydrogen halide is split off, whereupon the product is thermally decarboxylated.

2. The method according to claim 1, characterized in that one carries out the cyclization and hydrogen halide at 30-160 ° C.

3. The method according to claim 1 or 2, characterized in that one carries out the cyclization and hydrogen halide in the presence of a non-aqueous solvent.

4. The method according to claims 1 to 3, characterized in that one carries out the cyclization and hydrogen halide in the presence of a nitrogen base, an alkali metal acetate, carbonate or bicarbonate.

5. The method according to claim 4, characterized in that one uses ammonia or sodium acetate.

6. Process according to Claims 1 to 5, characterized in that the decarboxylation is carried out at 100-150 ° C.

7. The method according to claims 1 to 6, characterized in that one carries out the decarboxylation in the presence of an inert non-aqueous solvent.

8. The method according to claims 1 to 7, characterized in that one carries out both reaction stages in a reaction zone in the presence of a nitrogen base and an inert non-aqueous solvent at 70-160 ° C, preferably between 80 and 150 ° C.

9. The method according to claim 8, characterized in that ammonia is used as the nitrogen base and dimethylformamide is used as the solvent.

10. The method according to claims 1 to 9, characterized in that one works under anhydrous conditions.

11. The method according to claims 1 to 10, characterized in that one starts from compounds in which Rj and R2 are methyl groups.

2nd

R

f

35

Rr

/

/

/ ^ CHCOOR

CH ~ CH2-C (Hal) 2

3 (III)

CN

cyclized in the presence of a base and hydrogen halide 40 split off (X and Y are chlorine or bromine atoms, R3 is a hydrogen atom or an alkyl group with 1-4 C atoms), whereupon the cyclized product is thermally decarboxylated to form the compounds of the formula II which can be easily converted into the corresponding cyclopropanecarboxylic acids 45.

In the first stage of the process according to the inventive method, only mild temperature conditions, e.g. Room temperature, required. However, you can also work between 30 and 160 ° C. Higher temperatures above room temperature are generally preferred in order to carry out the reaction more quickly; 60-160 ° C is particularly suitable for this. The cyclization and elimination of hydrogen halide takes place simultaneously when mild conditions are used, e.g. in the presence of a 55% strength by weight solution of an alkali metal hydroxide in methanol at 20-30 ° C., which is mainly an intermediate of the general formula

I.

i

, CH2-C (Hal) 2

65

(IV)

COOR.

3rd

629 758

receives, wherein R4 is a hydrogen, alkali or alkaline earth atom, an ammonium group, which may optionally be alkali-substituted, or an alkyl group with 1-4 C atoms. The compounds of formula IV are new substances.

The cyclization and elimination of hydrogen halide must take place in the presence of a base, a weak base generally being sufficient, e.g. Hydroxides, acetates, carbonates and bicarbonates of alkali, alkaline earth or ammonium, and ammonia and alkyl-substituted ammonia, such as primary, secondary and tertiary amines. Good results are obtained with nitrogen bases and alkali acetates, carbonates and bicarbonates. Ammonia and sodium acetate are preferred.

The first process step is preferably carried out in the absence of water and in the presence of a non-aqueous solvent, such as an alkanol (methanol, ethanol) or dimethylformamide, the latter being particularly suitable.

The second process stage, namely decarboxylation, is preferably carried out between 100-150 ° C. It runs smoothly if one uses the free acid, its ammonium or alkali salt. A polar, aprotic solvent, such as dimethylformamide, is preferred for this process step.

It was surprisingly found that the two process steps can take place in the same reaction zone or in the same reactor and can also take place simultaneously. In other words, cyclization, hydrogen halide separation and decarboxylation appear to occur simultaneously. Such a combination of chemical reactions makes the process according to the invention particularly valuable with regard to the improved production of important pyrethroid-insecticide intermediates, such as 2- (2,2-dichlorovinyl) -3,3-dimethylcyclo-propanecarboxylic acid. As expected, the conditions for the combination of this reaction must be carefully selected in order to achieve an optimal end product.

According to the preferred embodiment of the process according to the invention, the synthesis takes place in a reaction zone or a reactor in the presence of a nitrogen base or sodium acetate and an inert, nonaqueous solvent at 70-160 ° C., preferably 80-150 ° C. The best results are obtained with ammonia or sodium acetate and dimethylformamide or N-methylpyrollidone as a non-aqueous solvent. Anhydrous conditions are preferred.

The compounds of formula IV are new, of these, 1-cyano-2- (2,2-dichlorovinyl) -3,3-dimethylcyclopropanecarboxylic acid is particularly preferred together with their alkali, alkaline earth metal and ammonium and substituted ammonium salts. These derivatives are valuable intermediates in the production of 2- (2,2-dichlorovinyl) -3,3-dimethylcyclopropanecarboxylic acid, the specific esters of which have insecticidal activity.

The invention is further illustrated by the following examples.

example 1

Preparation of 2- (2,2-dichlorovinyl) -3,3-dimethylcyclopropanenitrile (A)

1st stage (a)

Preparation of l-cyan-2- (2,2-dichlorovinyl) -3,3-dimethylcyclopropanecarboxylic acid (B)

64 g (0.166 mol) of methyl 4-bromo-2-cyan-3,3-dimethyl-6,6,6-trichlorohexanoate were added to a suspension of 120 g (1.8 mol) of potassium hydroxide in 2.11 within 25 minutes

Added methanol at 20 ° C, stirred at 35 ° C for one hour and then held at refluxing for 2.5 hours. The solvent was removed in vacuo and the residue was taken up in 1.51 water. The aqueous phase was washed once with dichloromethane and then acidified to pH ~ 1 with concentrated hydrochloric acid. The whole was then extracted three times with dichloromethane and the extracts dried. The solvent was removed under reduced pressure; white crystals were obtained in a yield of 37.6 g, 97%, mp.

128-132 ° C: l-cyan-2- (2,2-dichlorovinyl) -3,3-dimethylcyclopropane carboxylic acid. The NMR spectrum at 60 MHz in deuterochloroform solution showed the following bands compared to tetramethylsilane as standard, from which it follows that the product consisted of two geometric isomers Z and E, in a ratio Z: E = 56:44. 8 = 6.10ppm (doublet, -CH = Z-isomer)

8 = 5.78 ppm (doublet, -CH = E-isomer)

5 = 2.83 ppm (doublet, ring H E isomer)

8 = 2.65 ppm (doublet, ring H Z isomer)

8 = 1.60.1.38 ppm (singlet, 2 CH3 Z-isomer) 8 = 1.47.1.43 ppm (singlet, 2 CH3 E-isomer)

2nd stage (b)

Thermal decarboxylation of (B) 1.5 g of l-cyan-2- (2,2-dichlorovinyl) -3,3-dimethylcyclopropanecarboxylic acid was dissolved in 10 cm3 of dimethylformamide and the solution was saturated with ammonia gas at 20 ° C. for 18 h stirred at 130 ° C, diluted with 150 cm3 of water and extracted with pentane. The extracts were dried over magnesium sulfate and the solvent was removed under reduced pressure. 2- (2,2-dichlorovinyl) -3,3-dimethylcyclopropanenitrile was obtained in a yield of 82%.

Example 2

Example 1 was repeated with methyl 4-chloro-2-cyan-3,3-dimethyl-6,6,6-trichlorohexanoate as the starting material. 1-Cyan-2- (2,2-dichlorovinyl) -3,3-dimethyl-cyclopropanecarboxylic acid was obtained in a yield of 95-96%.

Example 3

First stage in a vessel with ammonia as the base 40 g of 4-chloro-2-cyan-3,3-dimethyl-6,6,6-trichlorhexyl acid were dissolved in 55 cm3 of dimethylformamide and the solution was saturated with ammonia at room temperature without cooling , 5 h at 140 ° C and then diluted with water and extracted three times with 100 cm3 ether. The ether solution was washed with saturated saline, dried over magnesium sulfate and evaporated. A yellow oil of compound A (purity 85%) was obtained, which partially crystallized on standing. Yield 79%.

Example 4

Preparation of A in a reaction vessel with sodium acetate as the base 3.07 g of 4-chloro-2-cyan-3,3-dimethyl-6,6,6-trichlorhexyl acid and 2.05 g of anhydrous sodium acetate were dissolved in 8 cm 3 of dimethylformamide and the solution was stirred at 145 ° C. for 12 h. The work-up corresponded to Example 3. Yield 185 g of compound A with a purity of 90%, this corresponds to 86%.

Example 5

Preparation of A in a reaction vessel with ammonia under pressure A solution of 6.14 g of 4-chloro-2-cyan-3,3-dimethyl-6,6,6-trichlorhexyl acid in 12 cm3 of dimethylformamide was

4 h at 145 ° C under an ammonia pressure of initially

Stirred 5 bar and then after lifting the pressure

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

629758

another 6 h, after which more than 90% solvent was stripped off after cooling (bath temperature max. 60 ° C, pressure 12 mmHg). The residue was taken up in toluene and washed successively with hydrochloric acid and sodium bicarbonate solution. After the organic phase was dried, the solvent was removed under reduced pressure. 3.3 g of 2- (2,2-dichlorovinyl) -3,3-dimethylcyclopropanenitrile were obtained; Yield 89%; Purity 97%.

Example 6

Preparation of A in a reaction vessel with N, N-diisopropyl-N-ethylamine as base A solution of 2.5 g of 4-chloro-2-cyano-3,3-dimethyl-5,6,6,6-trichlorohexyl acid in 2, 6 g of N, N-diisopropyl-N-ethylamine in 25 cm3 of dimethylformamide were heated to 145 ° C. for 5 hours and worked up as described in Example 3 after cooling to room temperature. Yield of 2- (2,2-dichlorovinyl) -3,3-dimethylcyclopropanenitrile 1.4 g; Purity 79% io corresponding to 73% yield.