CH644846A5 - ESTERS AND THIOESTERS OF AMINO ACIDS, THEIR USE FOR THE CONTROL OF PESTS AND THEIR PREPARATION. - Google Patents

Description

The present invention relates to new compounds according to claim 15 of their preparation according to claim 13 and according to claim 1, their use according to claim 12 and claims 15.

The compounds according to the invention corresponding to formula A,

CH. CH_

\! / 3

CH 0

R "

- CH - C - W - CH

(AT),

wherein each of the symbols R ', R2, R5, W, Y, Z and t have the meaning given in claim 1, are useful agents for the control of parasites such as insects and mites.

The compounds of formula A are prepared according to the following scheme:

YJ

CH CH_

3

CH 0

N - CH -

ï-o,

R "

OH + HO - CH

CH „CH ~

^ / 3

CH 0

- N - CH - C

N R2

R ~

0 - CH -

■ N.

0

(AT')

In carrying out the above synthesis, an acid, one of its salts or the acid chloride is reacted with an alcohol of formula II to form the carboxylic ester A '. For example, the acid chloride of the acid of formula I is reacted with an alcohol of formula II in an organic solvent such as diethyl ether in the presence of triethylamine. In another suitable embodiment, an acid of formula I and an alcohol of formula II are reacted in an organic solvent such as methylene chloride in the presence of 4-dimethylaminopyridine and cyclohexylcarbodiimide to form an ester of formula A '. The alcohol of formula II can be α-methyl- (6-phenoxypyridyl-2) -methanol, which can be obtained in a Grignard reaction between 6-phenoxypyridyl-2-carboxaldehyde and methylmagnesium bromide. In another suitable embodiment, the esters of formula A ′ are prepared by reacting an acid of formula I with phosgene in the presence of an ether such as 1,4-dioxane to form the oxazolidinedione (2, 5) corresponding which is then reacted with an alcohol of formula II to form the corresponding ester of formula A '. In another suitable synthesis, the acid of formula I or one of its salts is reacted with the bromide, chloride or mesylate of alcohol of formula II to form an ester of formula A '. The raw materials of formula I are described in application DE-OS No. 2812169. It is possible to prepare

644,846

4

rer alcohols of formula as described in the application DE-OS N ° 2810881 and in Maeda and Hirose, "CA", 81,13596k and 80, 58873s, as well as in the references which are cited there.

In another embodiment, the compounds of formula A are prepared by reacting an amine (III) with an a-halo-ester of formula IV (X being a bromine or chlorine atom).

(III)

CH1

\ / 3 5

CH O R I II 1

X-CH-C-O-CH

The reaction of the amine (III) and the haloester (IV) is generally carried out without solvent or in an organic solvent such as phosphoric hexamethyltriamide, tetrahydrofuran, dimethylformamide, dimethylsulfoxide, etc. The haloesters of formula IV can be prepared by reacting a corresponding acid halide with an alcohol of formula II.

The thioesters of formula A can be prepared, for example, by reacting the sodium salt of a thioacid of formula I with the bromide or alcohol mesylate of formula II.

The compounds of formula A according to the invention contain one or more asymmetric carbon atoms. The invention encompasses each of the optical isomers and their racemic mixtures. In the examples below, unless otherwise indicated, the compound prepared is a racemic mixture.

The invention encompasses the salts of the compounds of formula A. The salts are formed with strong mineral or organic acids, such as hydrochloric, sulfuric, phosphoric, p-toluenesulfonic, benzenesulfonic, methanesulfonic, Lewis acids, etc. Many of the compounds of formula A are oils which are advantageously converted into salt to provide more convenient handling and dosage and greater stability. The salts are useful for controlling parasites in the same way as the compounds of formula A.

The compounds of formula A according to the invention are useful pesticides, particularly for the fight against insects and mites. When using the compounds of formula A for the control of insects and mites and the protection of crops, for example soybeans, cotton, alfalfa, etc., it is applied to the plot, in an effective amount in as a pesticide, a compound of formula A or a mixture of these compounds with a carrier or vehicle. The support can be liquid or solid and include adjuvants such as wetting agents, dispersing agents and other surfactants. The compounds of formula A can be used in compositions such as wettable powders, solutions, dusting powders, granules, emulsifiable concentrates, etc. Suitable solid supports include natural and synthetic silicates and clays, carbon or charcoal granules, natural and synthetic resins, waxes, etc. Suitable liquid carriers include water, aromatic hydrocarbons, alcohols, vegetable and mineral oils, ketones, etc. The amount of compounds of formula A in the composition can vary widely, generally from about 0.01 to 90.0% by weight.

As indicated below, the compounds of the invention are effective on many different insects and on mites. The compounds are effective in controlling insects such as mosquitoes, flies, aphids and weevils and against mites such as red spiders and ticks. Depending on the particular combination of the substituents of formula A, the compounds have a broad or relatively narrow spectrum of pesticidal activity, exceptionally high on insects and mites. Among the parasites against which the compounds of the invention have a pesticidal effectiveness include insects of the orders Lepidoptera, Orthoptera, Heteroptera, Homoptera, Diptera, Beetles io and Hymenoptera, as well as mites of the families of tetany -chids and tarsonemids and ticks such as ornithodoros.

The compounds of the invention can be used in combination with other pesticides such as carbamates, phosphates and insect growth regulators such as propoxur, carba-15 ryl, naled, dichlorvos, methoprene, kinoprene, hydro-prene, cyhexatin, resmethrin, fenvalerate, permethrin and fluvalivate.

The following examples are given by way of nonlimiting examples to illustrate the implementation of the invention.

20

Example 1:

To a stirred solution of 0.2 g (0.99 mmol) of (6-phenoxypyridyl-2) -methanol and 0.14 g (1.38 mmol) of triethylamine in approximately 15 ml of ether, under nitrogen, add a solution of 1.5 mmol of the acid chloride of N (2-chloro-4-tri-fluoromethylphenyl) valine in ether using a syringe. The mixture is stirred for 30 min, then the reaction is stopped with a saturated aqueous solution of sodium bicarbonate. The ethereal phase is washed with gaseous sodium bicarbonate, water and brine and filtered through silica. The solvent is evaporated, then a thin layer chromatography is carried out using a circular chromatograph, eluting with 20% ether in hexane and the (6-phenoxypyridyl-2) -methyl ester is obtained. N- (2-chloro-4-tri-fluoromethylphenyl) valine, a practically colorless viscous oil.

35

Example 2:

A. To a solution of 0.37 g (1.8 mmol) of 6-phenoxypyridyl-2-carboxaldehyde in 25 ml of ether, 25 ml of water is added, then 0.149 g (3.05 mmol) of cyanide sodium. The mixture is vigorously stirred while adding, over a period of about 5 min, a solution of 0.257 g (2.47 mmol) of sodium bisulfite in 15 ml of water. The mixture is stirred for 2 h. The organic phase is separated, washed with water, dried over calcium sulfate and the solvent is evaporated to obtain cyano- (6-phenoxypyridyl-2) -methanol. 45 B. To 2.5 mmol of the acid chloride of N- (2-fluoro-4-trifluoro-methylphenyl) valine in ether, 1.3 ml of triethylamine are added, then the cyano- (6 -phenoxypyridyl-2) -methanol in 5 ml of ether, coming from part A above, in about 2 min. The mixture is stirred for about 18 h, then the reaction is stopped using saturated aqueous sodium bicarbonate. The organic phase is washed with aqueous sodium bicarbonate, water and brine, dried over calcium sulfate and the solvent is evaporated. The crude product is chromatographed on a circular chromatograph, eluted with 20% ether in hexane and the N- (2-fluoro) cyano- (6-phenoxypyridyl-2) -methyl ester is obtained. -4-trifluoromethylphenyl) valine, which is a pale yellow viscous liquid.

Example 3:

fio To a stirred solution of 410 mg (1.8 mmol) of cyano- (6-phenoxypyridyl-2) -methanol, 590 mg (2.0 mmol) of N- (2-chloro-4-trifluoromethylphenyl) valine and 0.665 mmol of dimethylamino-pyridine in 20 ml of methylene chloride and 2 ml of dimethylformamide, 2.0 mmol of N, N'-dicyclohexylcarbodiimide is added. The mixture is stirred under nitrogen for 2 h, then filtered and extracted with water. The aqueous phase is extracted with ether. The organic phases are combined, washed with saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride,

5

644,846

dried over calcium sulfate and the solvent is evaporated. The crude product is chromatographed on a rotary chromatograph eluting with 25% ether in hexane to obtain the cyano- (6-phenoxypyridyl-2-methyl ester of N- (2-chloro-4-trifluoromethyl). -phenyl) valine, which is a viscous, colorless liquid.

The cyano- (6-phenoxy-pyridyl-2) -methyl ester of N- (2-chloro-4-difluoromethoxyphenyl) -valine, MS m / e 500 (M +) is prepared in a similar manner.

Example 4:

To a solution of 336 mg (1.32 mmol) of 3- (4-chlorophenyl) -4-isopropyloxazolidinedione (2.5) and dimethylamino-pyridine in 5 ml of dry tetrahydrofuran, a solution of 254 mg is added. (1.26 mmol) of (6-phenoxypyridyl-2) -methanol in 3 ml of dry tetrahydrofuran. The mixture is stirred for about 20 h in dry air, then diluted with ether and then washed with saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride. After drying over calcium sulfate, the solvent is evaporated. The crude product, which is a yellow liquid, is chromatographed on a rotary chromatograph eluting with 15% ether in hexane to obtain the (6-phenoxy-pyridyl-2-methyl ester of N- ( 4-chlorophenyl) valine, which is a colorless oil.

By the same process as above, 3- (4-methyl-phenyl) -4-isopropyloxazolidinedione (2,5) is reacted with (6-phenoxy-pyridyl-2) -methanol to obtain the ester of (6-phenoxy-pyridyl-2) -methyl of N- (4-methylphenyl) valine.

Similarly, 3- (4-trifluoromethyl-phenyl) -4-isopropyloxazolidinedione (2,5) is reacted with (6-phenoxy-pyridyl-2) -methanol to obtain the (6-phenoxy) ester. -pyridyl-2) -methyl of N- (4-trifluoromethylphenyl) valine.

Example 5:

Using the method of Example 3, each of the acids is reacted on cyano- (6-phenoxypyridyl-2) -methanol: N- (4-chloro-2-fluorophenyl) valine, N- (2-fluoro- 4-methylphenyl) valine, N- (2,4-dichlorophenyl) valine, N- (4-trifluoromethylphenyl) valine, N- (2-chloro-4-methylphenyl) valine and N- (4-difluoromethoxyphenyl) valine to obtain l '' respective ester, namely:

the cyano- (6-phenoxypyridyl-2) -methyl ester of N- (4-chloro-2-fluorophenyl) valine,

the cyano- (6-phenoxypyridyl-2) -methyl ester of N- (2-fluoro-4-methylphenyl) valine,

the cyano- (6-phenoxypyridyl-2) -methyl ester of N- (2,4-dichlorophenyl) valine,

the cyano- (6-phenoxypyridyl-2) -methyl ester of N- (4-tri-fluoromethylphenyl) valine,

the cyano- (6-phenoxypyridyl-2) -methyl ester of N- (2-chloro-4-methylphenyl) valine,

the cyano- (6-phenoxypyridyl-2) -methyl ester of N- (4-difluoromethoxyphenyl) valine.

Example 6:

The N- (4-fluorophenyl) valine or 2- (4-fluoro-phenylamino) -3-methylbutanoic acid is reacted with cyano- (6-phenoxy-pyridyl-2) -methanol according to the method of Example 3 to obtain the cyano (6-phenoxypyridyl-2) -methyl ester of N- (4-fluorophenyl) valine or 2- (4-fluorophenylamino) -3-cyano- (6-phenoxypyridyl-2) methylbutanoate -methyl.

Likewise, according to the method of Example 3, each of the acids indicated below in I is reacted on cyano- (6-phenoxypyridyl-2) -methanol to obtain the esters illustrated in II:

I

2- (4-methylphenylamino) -3-methylbutanoic acid 2- (4-chlorophenylamino) -3-methylbutanoic acid 2- (4-methoxyphenylamino) -3-methylbutanoic acid 2- (4-ethylphenylamino) -3-methylbutanoic acid

II

Cyano- (6-phenoxypyridyl-2) -methyl 2- (4-methylphenylamino) -3-methylbutanoate acid,

Cyano- (6-phenoxypyridyl-2) -methyl 2- (4-chlorophenylamino) -3-methylbutanoate acid,

Cyano- (6-phenoxypyridyl-2) -methyl 2- (4-methoxyphenylamino) -3-methylbutanoate acid,

Cyano- (6-phenoxypyridyl-2) -methyl 2- (4-ethylphenylamino) -3-methylbutanoate acid.

Example 7:

The 2- (2-chloro-4-trifluoromethylphenyl-amino) -3-methylbutanoyl chloride is reacted with the [6- (4-fluorophenoxy) -pyridyl-2] -methanol according to the method of Example 1 to obtain 2- (2-chloro-4-trifluoromethylphenylamino) -3-methylbutanoate of [6- (4-fluorophenoxy) -pyridyl-2] -methyl, MS m / e 496 (M +).

Example 8:

To a mixture of 2.63 mmol of 2- (2-chloro-4-trifluoro-methylphenylamino) -3-methylbutanoic acid, 5 ml of cold methylene chloride and 0.21 mmol of dimethylaminopyridine, at 0 ° C., add 2.79 mmol of a-methyl- (6-phenoxypyridyl-2) -methanol in 2 ml of methylene chloride, then 2.61 mmol of dicyclohexyl-carbodiimide. The mixture is stirred at ambient temperature for approximately 47 h, then it is treated as in Example 3. The crude product is chromatographed in a thin layer, eluting with 30% ether in hexane to obtain 2- (2-chloro-4-trifluoro-methylphenylamino) -3-methyl-a-methyl- (6-phenoxy-pyridyl-2) -methylbutanoate, MS m / e 492 (M +).

To prepare the alcohol which is α-methyl- (6-phenoxy-pyridyl-2) -methanol, a Grignard reaction is carried out between 6-phenoxypyridyl-2-carboxaldehyde and methyl magnesium bromide in tetrahydrofuran . 6-phenoxy-pyridyl-2-carboxaldehyde is obtained by oxidizing 6-phenoxy-pyridyl-2-methanol using chromium trioxide and pyridine in methylene chloride.

Using the method of this example, reacting 2- (2-chloro-4-trifluoromethylphenylamino) -3-methylbutanoic acid with a-methyl- [6- (4-fluorophenoxy) pyridyl-2] -methanol to obtain 2- (2-chloro-4-trifluoromethylphenylamino) -3-methylbutanoate a-methyl- [6- (4-fluorophenoxy) pyridyl-2] -methyl. Similarly, 2- (2-fluoro-4-trifluoromethylphenyl-amino) -3-methylbutanoic acid is reacted with a-methyl- (6-phenoxy-pyridyl-2) -methanol to obtain 2- (2-fluoro-4-trifluoromethyl-phenylamino) -3-methylbutanoate a-methyl- (6-phenoxy-pyridyl-2) -methyl, MS m / e 476 (M +).

Example P. Following the procedure of Example 8, the 2- (2-chloro-4-trifluoromethylphenylamino) -3-methylbutanoic acid is reacted with α-ethynyl- (6-phenoxypyridyl-2) -methanol to obtain 2- (2-chloro-4-trifluoromethylphenylamino) -3-methyl-abutynate- (6-phenoxypyridyl-2) -methylbutanoate, MS m / e 502 (M +).

The above alcohol is prepared by a Grignard reaction between 6-phenoxypyridyl-2-carboxaldehyde and ethynylma-gnesium bromide in tetrahydrofuran.

Example 10:

To 0.29 g of 2- (2-chloro-4-trifluoromethylphenyl-amino) -3-methylbutanoic acid in 10 ml of benzene, 0.21 g of oxalyl chloride and dimethylformamide is added at room temperature. After approximately 5 min, the solution is heated to approximately 40 ° C., the solvent and the excess oxalyl chloride are removed. Then added to the acid chloride in tetrahydrofuran 0.2 g of (6-phenoxypyridyl-2) -methylthiol and 0.22 g of dimethylaminopyridine with stirring. The mixture is stirred for approximately 18 h, then it is treated with ether, washed with water and brine and dried over sodium sulfate. The reaction product is chromatographed on plates

5

10

15

20

25

30

35

40

45

50

55

60

65

644,846

6

using 20% ethyl acetate in hexane to obtain the S- (6-phenoxypyridyl-2) -methyl 2- (2-chloro-4-trifluoromethylphenylamino) -3-methylbutanoic acid thioester , MS m / e 494 (M +) (formula A in which W is a sulfur atom, Y is a chlorine atom, t = 1, Z is a trifluoromethyl group. And R ', R2 and 5 R5 are d atoms 'hydrogen).

Similarly, the thioester of S- (6-phenoxy-pyridyl-2) -methyl of 2- (2-fluoro-4-trifluoromethylphenyl-amino) -3-methylbutanoic acid, MS m / e 478 is prepared. M +).

io

Example 11:

A. To a solution, cooled to approximately 5 ° C., of 3.38 mmol of 2- (2-chloro-4-trifiuoromethylphenylamino) -3-methyl-butanoic acid in 25 ml of dimethylformamide, 3.38 mmol is added of triethylamine and 3.38 mmol of ethyl chloroformate. The mixture is stirred for approximately 15 min, then 6.76 mmol of sodium hydrosulfide and 10 ml of dimethylformamide are added. The mixture is stirred at

5 ° C for approximately A h. Ether is added to the mixture, then acidified with 5% H 2 SO 4. The ethereal layer is washed with water and brine, dried over sodium sulfate and the solvent is evaporated to give the 2- (2-chloro-4-trifluoromethylphenylamino) -3- acid thioacid methylbutanoic.

B. To 15 ml of dimethylformamide and 10 ml of tetrahydrofuran, 1.60 mmol of α-cyano- (6-phenoxy-) mesylate are added.

pyridyl-2) -methanol. The mixture is stirred at room temperature for about 18 h. The mixture is taken up in ether, washed with water and brine, dried over sodium sulfate and the solvent is removed to obtain the thioester of Sa-cyano- (6-phenoxy-pyridyl-2) -methyl of 2- (2-chloro-4-trifluoromethylphenyl-amino) -3-methylbutanoic acid.

Similarly, the thioester of Sa-methyl- (6-phenoxypyridyl-2) -methyl of 2- (2-chloro-4-trifluoromethyl-phenylamino) -3-methylbutanoic acid MS m / e 508 (M +) is prepared. ) and the thioester of 5-a-methyl- (6-phenoxypyridyl-2) -methyl of 2- (2-fluoro-4-trifluoromethylphenylamino) -3-methylbutanoic acid MS m / e 492 (M +).

Two groups are taken, each comprising 10 larvae of Heliothis virescens of third stage from 0 to 24 h, and they are treated with 1 μl of 2- (2-chloro-4-trifluoromethylphenylamino) -3-methylbutanoate (6-phenoxypyridyl- 2) -methyl in acetone at five different concentrations by application to the back of the thorax. Two groups of 10 larvae each are treated identically with 1 μl of acetone only, as a control. The larvae are kept individually in 30 ml plastic cups containing an artificial medium for 72 h at 25 ° C. with a 16 h photoperiod. After 72 h, the number of deaths is calculated as a percentage of the total number initially treated, then it is corrected for any mortality in the control groups using the Abbot formula. The LD50 of the compound is less than 0.05%.

R

Claims (5)

644,846 1. Compounds corresponding to formula A acetyl or formyl; and Rs is a hydrogen atom or a cyano, ethynyl or methyl group; as well as the salts formed by these compounds with a strong mineral or organic acid. 2. Compounds according to claim 1, characterized in that R2 is a hydrogen atom or a methyl group and t is 0 or 1. 2 3 644,846 N - H on an a-haloester of formula IV CH CH, \ / 5 , »L) ÇH 0 R 3. Compounds according to claim 1, characterized in that they correspond to the formula in which: R 'is a hydrogen or fluorine atom; 15 W is an oxygen or sulfur atom; t is 0.1 or 2; Y is a hydrogen, chlorine or fluorine atom; Z is a chlorine or fluorine atom or a trifluoromethyl, methoxy, methyl, ethyl, difluoromethoxy or trifluoromethoxy group; R2 is a hydrogen atom or a methyl, ethyl group, R ' in which t is 0 or 1 and R2 is a hydrogen atom or a methyl group. 4. Compounds according to claim 3, characterized in that t = 0. 5. Compounds according to claim 3, characterized in that t = l. 6. Compounds according to claim 3, characterized in that t = 1, W is an oxygen atom, Y is a chlorine or fluorine atom and Z is a trifluoromethyl group. 7. Compounds according to claim 6, characterized in that R2 is a hydrogen atom and Rs is a hydrogen atom or a cyano or methyl group. 8. Compounds according to claim 6, characterized in that R2 is a hydrogen atom and Rs is a cyano group. 9. Compounds according to claim 6, characterized in that R2 and R5 are hydrogen atoms. 10. Compounds according to claim 3, characterized in that W is a sulfur atom, R2 is a hydrogen atom, t = 0 and R5 is a cyano group. 11. Compounds according to claim 3, characterized in that W is a sulfur atom, R2 is a hydrogen atom, t = 1, Y is a chlorine or fluorine atom, Z is a trifluoromethyl group and R5 is a hydrogen atom or a cyano group. 12. Composition for the fight against parasites or their habitat, comprising an effective amount of the compounds according to one of claims 1 to 11, associated with suitable inert supports. 13. Process for the preparation of compounds of formula A, in which W is an oxygen atom, according to claim 1, characterized in that an acid of formula I is reacted 40 CH CH_ S3 / 3 CH 0 (I) / iV-n-JH -! - OH 45 Z Ä2 or a salt thereof or the acid chloride with an alcohol of formula II in an organic solvent. 14. Method according to claim 13, characterized in that, for the preparation of a compound of formula A, in which W is 60 an oxygen atom, R 'is a hydrogen atom and R2 is a methyl group, 6-phenoxypyridyl-2-carboxaldehyde is reacted in a Grignard reaction with methyl magnesium bromide in tetrahydrofuran and reacts the α-methyl- (6-phenoxypyridyl-2) -methanol thus obtained with an acid of formula I 65 according to the process according to claim 14. 15. Process for the preparation of compounds of formula A, in which W is an oxygen atom, according to claim 1, characterized in that an amine of formula III is reacted 5 X-CH-C-O-CH in which X is a bromine or chlorine atom.