EP0788484A1

EP0788484A1 - 2-chloro-n- 1-(2,6-dichloro-4-difluoromethyl-phenyl)-1h-pyrazol-5-yl]-propanamide and a method of producing the same

Info

Publication number: EP0788484A1
Application number: EP95936468A
Authority: EP
Inventors: Hans-Joachim Knops; Bernd Gallenkamp; Lothar Rohe
Original assignee: Bayer AG
Current assignee: Bayer AG
Priority date: 1994-10-24
Filing date: 1995-10-11
Publication date: 1997-08-13
Also published as: DE4437930A1; WO1996012707A1; AU3840895A

Abstract

The invention concerns the novel compound 2-chloro-N-[1-(2,6-dichloro-4-difluoromethyl-phenyl)-1H-pyrazol-5-yl]-propanamide of formula (I), a method of producing said compound and the use thereof as starting material for the production of the herbicidal compound 2-chloro-N-[1-(2,6-dichloro-4-difluoromethyl-phenyl)-4-nitro-1H-pyrazol-5-yl]-propanamide of formula (II).

Description

2-Chloro-N- (1- (2,6-di-chloro-4-difluoroethyl-phenyl) -IH-pyrazole-5-yl) -pro _D anami d and a method to be used Manufacture

The invention relates to the new compound 2-chloro-N- [1- (2,6-dichloro-4-difluoromethylphenyl) -1H-pyrazol-5-yl] propanamide and a process for its preparation.

It is known that certain arylpyrazoles can be used as herbicides or as intermediates for the preparation of herbicides (cf. EP-A 303 153). The 2 to be used as an intermediate for the preparation of the compound — chlorine-N- [l- (2,6-dichloro-4-difluoromethylphenyl) -4-nitro-lH-pyrazol-5-yl] propanamide, which is particularly interesting as a herbicide -Chlor-N- [1- (2-6-dichloro-4-difluoromethyl-phenyl) -1H-pyrazol-5-yl] propanamide is not yet known from the literature.

The new compound 2-chloro-N- [l- (2,6-dichloro-4-difIuormethylphenyl) -lH-pyrazol-5-yl] propanamide of the formula (I)

Found. It was also found that the new compound 2-chloro-N- [1- (2,6-dichloro-4-difluoromethyl-phenyl) -1H-pyrazol-5-yl] propanamide of the formula (I) was very good The yield and high purity is obtained if, in a first step, the compound 3- [2- (2,6-dichloro-4-trifluoromethylphenyl) hydrazino] propane nitrile of the formula (II)

with a base in the presence of a diluent under an inert gas atmosphere at temperatures between 0 ° C and 150 ° C, the resulting compound 1 - (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-amine of the formula (III)

isolated and reacted in a second stage with 2-chloropropionic acid chloride, optionally in the presence of an acid acceptor and optionally in the presence of a diluent at temperatures between -20 ° C. and + 100 ° C.

Surprisingly, the novel compound of the formula (I) can be obtained in the yield according to the invention in considerably higher yield than in the case of synthesis carried out analogously (cf. EP-A 303153). The method according to the invention thus represents a valuable addition to the prior art.

The course of the reaction in the process according to the invention can be represented by the following formula:

The compound 3- [2- (2,6-dichloro-4-trifluoromethylphenyl) hydrazino] propane nitrile of the formula (II) to be used as starting material in the process according to the invention is known and can be prepared by a known process (see EP-A 303 53).

The process according to the invention is preferably carried out in the first stage in the presence of a suitable base. All customary inorganic or organic bases are suitable as such. These include, for example, alkali metal or alkaline earth metal hydrides, hydroxides, amides, alcoholates, acetates, carbonates or hydrogen carbonates, such as, for example, lithium, sodium, potassium or calcium hydride, lithium, sodium or Potassium amide, sodium or potassium methylate, sodium or potassium ethylate, sodium or potassium propylate, aluminum isopropylate, sodium or potassium tert-butoxide, sodium or potassium hydroxide, ammonium hydroxide, sodium, Potassium or calcium acetate, ammonium acetate, sodium, potassium or calcium carbonate, ammonium carbonate, sodium or potassium hydrogen carbonate, and basic organic nitrogen compounds, such as trimethylamine, triethylamine, tripropylamine, tributylamine, ethyldiisopropylamine, N, N- Dimethylcyclohexylamine, dicyclohexylamine, ethyl-dicyclohexylamine, N, N-dimethylaniline, N, N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl- and 4-methyl-pyridine, 2,4-dimethyl-, 2 , 6-dimethyl-, 3,4-dimethyl- and 3,5-dimethyl-pyridine, 5-ethyl 2-methyl-pyridine, N-methylpiperidine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclonones (DBN) or diazabicycloundecene (DBU)

Alkali metal hydroxides, e.g. Sodium hydroxide or potassium hydroxide, or alkali metal alcoholates such as e.g. Sodium or potassium methanolate, ethanolate, n or i

Propanolate, -n-, -i-, -s- or -t-butanolate, -n-, -i-, -s- or -t-pentanolate are considered as Bases to be used in the first stage in the process according to the invention are particularly preferred

Suitable diluents for carrying out the first stage of the process according to the invention are the customary organic solvents. These include, in particular, aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, pentane, hexane, heptane, petroleum ether, ligroin, gasoline, benzene, Toluene, xylene, chlorobenzene, dichlorobenzene, cyclohexane, methylcyclohexane, dichloromethane, chloroform, carbon tetrachloride, ethers, such as diethyl ether, diisopropyl ether, t-butyl methyl ether, t-pentyl methyl ether, dioxane, tetrahydrofuran, ethylene glycol dimethyl - or diethyl ether, diethylene glycol dimethyl ether or diethyl ether, ketones such as acetone, butanone or methyl isobutyl ketone; Nitriles, such as acetonitrile, propionitrile, butyronitrile or benzonitrile; Amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric acid triamide; Esters such as methyl acetate, ethyl ester, n- or i-propyl ester, n-, i- or s-butyl ester, sulfoxides such as dimethyl sulfoxide, alcohols such as methanol, ethanol, n- or i- Propanol, n-, i-, s- or t-butanol, ethylene glycol monomethyl ether or monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, their mixtures with water or pure water

Alcohols, e.g. Methanol, ethanol, n- or i-propanol are particularly preferred as diluents when carrying out the first stage of the process according to the invention.

The first stage of the process according to the invention is carried out under an inert gas atmosphere. The usual inert gases, preferably nitrogen or argon, are suitable here.

The reaction temperatures can be varied within a substantial range when carrying out the first stage of the process according to the invention. In general, temperatures between 0 ° C and 150 ° C, preferably at temperatures between 10 ° C and 120 The first stage of the process according to the invention is generally carried out under normal pressure. However, it is also possible to work under increased or reduced pressure - generally between 0.1 bar and 10 bar.

To carry out the first stage of the process according to the invention, generally from 1.0 to 5 per mole of 3- [2- (2,6-dichloro-4-trifluoromethylphenyl) hydrazino] propane nitrile of the formula (II) 0 mol, preferably 1.5 to 2.5 mol of a base.

In a preferred embodiment of the first stage of the process according to the invention, the starting compound of the formula (II) is placed in a suitable diluent and the air present in the reaction vessel is then replaced by an inert gas, preferably at elevated temperature. Then a base - preferably dissolved in a diluent such as water or one of the abovementioned alcohols and preferably treated with an inert gas before the addition - is metered in and the reaction mixture is stirred at the required temperature under an inert gas atmosphere until the reaction has ended.

Working up to isolate the product of the first stage - the compound of the formula (III) - can be carried out in the customary manner. For example, the mixture is diluted to 2 to 5 times the volume with water and, after stirring for a long time with cooling, the crystalline product is isolated by suction. It can be further purified by recrystallization, for example from xylene / cyclohexane.

The second stage of the process according to the invention is preferably carried out in the presence of a suitable acid acceptor. All customary organic or organic bases are suitable as such. These include, for example, alkali metal or alkaline earth metal hydrides, hydroxides, amides, alcoholates, acetates, carbonates or hydrogen carbonates, such as, for example, lithium, sodium, potassium or calcium hydride, lithium, sodium - or potassium amide, sodium or potassium methylate, sodium or potassium ethylate, sodium or potassium propylate, aluminum isopropylate, sodium or potassium tert-butoxide, sodium or potassium hydroxide, ammonium hydroxide, sodium -, potassium or calcium acetate, ammonium acetate, sodium, potassium or calcium carbonate, ammonium carbonate, sodium or potassium hydrogen carbonate, and also basic organic nitrogen compounds, such as trimethylamine, triethylamine, tripropylamine, tributylamine, ethyldiisopropylamine, N, N-dimethyicyclohexylamine, dicyclohexylamine, ethyl-dicyclohexylamine, N, N-dimethyl-methylanihn, N, N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl- and 4-methyl-pyπdin, 2,4- Dimethyl-, 2,6-dimethyl-, 3,4-dimethyl- and 3,5-dimethyl-pyπdin, 5-ethyl-2-methyl-pyπdιn, N-methylpipendin, N, N-dim-dimethylamιnopyπdιn, diazabicyclooctane (DABCO), Diazabicyclonones (DBN) or diazabicycloundecen (DBU)

Pyπdin is particularly preferred as an acid acceptor

The customary organic solvents are suitable as diluents for carrying out the second stage of the process according to the invention. These include in particular aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, pentane, hexane, heptane, petroleum ether, ligroin, gasoline, benzene, toluene, Xylene, chlorobenzene, dichlorobenzene, cyclohexane, methylcyclohexane, dichloromethane, chloroform, carbon tetrachloride, ethers, such as diethyl ether, diisopropyl ether, t-butyl methyl ether, t-pentyl methyl ether, dioxane, tetrahydrofuran, ethylene glycol dimethyl or diethyl glycol, diethyl ether - Dimethyl ether or diethyl ether, ketones, such as acetone, butanone or methyl isobutyl ketone, nitls, such as acetonitrile, propionitrile, butyronitol or benzonitol, amides, such as N, N-dimethylformamide, N, N-dimethyl acetamide, N-methyl formam , N-Methyl-pyrrohdon or Hexamethylphosphorsauretπamid, esters such as methyl acetate, ethyl acetate, -n- or -i-propyl ester, -n-, -I- or -s-butyl ester, sulfoxides, such as dimethyl sulfoxide

When carrying out the second stage of the process according to the invention, the reaction temperatures can be varied within a substantial range. In general, temperatures between -20 ° C. and + 100 ° C., preferably at temperatures between 0 ° C. and 100 ° C.

The second stage of the process according to the invention is generally carried out under normal pressure. However, it is also possible to work under increased or reduced pressure - generally between 0.1 bar and 10 bar

To carry out the second stage of the process according to the invention, 1 - (2,6-di-chloro-4-difluoromethyl-phenyl) -1H-pyrazole-5-amine of the formula (III) is used per mole generally 1.0 to 1.5 moles, preferably 1.05 to 1.2 moles of 2-chloropropionic acid chloride.

In a preferred embodiment of the second stage of the process according to the invention, the compound of the formula (III) is placed in a suitable diluent and an acid acceptor is added. The 2-chloropropionic acid chloride is then slowly metered in and the reaction mixture is stirred until the reaction has ended.

Working up to isolate the second stage product - the compound of formula (I) - can be carried out in a conventional manner. For example, it is diluted to 2 to 5 times the volume with water and, after stirring for a long time, the crystalline product is isolated by suction

The compound of the formula (I) to be prepared by the process according to the invention can be used as starting material for the preparation of the herbicidally active compound 2-chloro-N- [l- (2,6-dichloro-4-difluoromethyl-phenyl) -4-nitro-1H- pyrazol-5-yl] propanamide (cf. EP-A 303153) can be used according to the following formula:

CHF "

Manufacturing examples

step

10.3 g (34.5 mmol) of 3- [2- (2,6-dichloro-4-trifluoromethyl-phenyl) -hydrazino] -propane-nitπl are dissolved in 20 ml of ethanol and heated to boiling under reflux for 15 minutes , the air in the reaction vessel being displaced by introducing nitrogen. With further introduction of nitrogen, the solution is cooled to 20.degree. C. and then a solution of 5.9 g of 45% strength aqueous sodium hydroxide solution (66 mmol of NaOH) saturated with nitrogen is metered in over the course of 20 minutes The reaction mixture is refluxed for about 60 minutes and stirred for a further 20 hours at about 20 ° C. Then the mixture is poured onto 85 ml of water and stirred for 2 hours at 10 ° C. The product which crystallizes is isolated by suction, dried and extracted from 40 ml of xylene / Cyclohexane (Vol 1 1) recrystallized

7.7 g (content 99.6%, ie yield 80% of theory) are obtained 1 - (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-amine with a melting point of 1 1 1 ° C.

Level 2

9.6 g (34.8 mmol) of l- (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-amine are placed in 40 ml of acetonitrile and at 20 ° C. with 3.44 g of pyridine transferred. Then 4.8 g (37.0 mmol) of 2-chloro-propionic acid chloride are added dropwise at 15 ° C. to 20 ° C. while stirring, the reaction mixture is stirred at 20 ° C. for 12 hours and then poured onto 100 ml of ice water. After stirring for three hours, the crystalline product is isolated by suction and dried.

1 1.3 g (content 96.7%, ie yield: 88% of theory) of 2-chloro-N- [l- (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazole- 5-yl] -propanamid / on 5 melting point 87 ° C.

Conversion example:

H, 2g (30.6 mmol) 2-chloro-N- [l- (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-yl] propanamide are initially charged in 40 ml acetic acid and at 10 ° C to 15 ° C with 3.75 ml (39 mmol) of acetic anhydride. Then 1.6 ml (38 mmol) of nitric acid (100%) are added dropwise at 10 ° C. to 15 ° C. while stirring, the reaction mixture is stirred for 20 hours at approx. 20 ° C. and then to 100 ml Given water. After stirring for two hours, the crystalline product is isolated by suction and dried.

1 1.3 g (content: 88%, ie yield, 79% of theory) of 2-chloro-N- [l- (2,6-dichloro-4-difluoromethylphenyl) -4-nitro-1H- pyrazol-5-yl] -propanamide with melting point 1 13 ° C.

Claims

Claims:

2-chloro-N- [l - (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-yl] propane amide of the formula (I)

2. Process for the preparation of 2-chloro-N- [l- (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-yl] propanamide of the formula (I)

characterized in that in a first stage the compound 3- [2- (2,6-dichloro-4-trifluoromethylphenyl) hydrazino] propane nitrile of the formula (II)

CF, with a base in the presence of a diluent under an inert gas atmosphere at temperatures between 0 ° C and 150 ° C, the resulting compound l- (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-amine of the formula (III)

isolated and in a second stage with 2-chloro-propionic acid chloride, optionally in the presence of an acid acceptor and optionally in the presence of a diluent at temperatures between -20 ° C and + 100 ° C.

3 A process for the preparation of 2-chloro-N- [l- (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-yl] -propanamide according to claim 2, characterized gekenn¬ characterized in that this in the first stage at temperatures between 10 ° C and 120 ° C and in the second stage at temperatures between -20 ° C and + 100 ° C

4. A process for the preparation of 2-chloro-N- [1- (2,6-dichloro-4-difluoromethyl-phenyl) -1H-pyrazol-5-yl] propanamide according to claim 2, characterized in that: performs the first and second stages under normal pressure.

5 A process for the preparation of 2-chloro-N- [l- (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-yl] -propanamide according to claim 2, characterized in that the carries out the first stage under inert gas

6 Process for the preparation of 2-chloro-N- [1- (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-yl] -propanamide according to claim 2, characterized records that in the first stage per mole of 3- [2- (2,6-dichloro-4-trifluoromethylphenyl) hydrazino] propane nitrile of the formula (II)

1.0 to 5.0 moles of base are used and in the second stage per mole of l- (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-amine of the formula (III)

1.0 to 1.5 moles of 2-chloropropionic acid chloride are used.

Process for the preparation of 2-chloro-N- [1- (2,6-dichloro-4-difluoromethyl-phenyl) -4-nitro-1H-pyrazol-5-yl] -propanamide, characterized in that 2-chloro -N- [l- (2,6-dichloro-4-difluoromethyl-phenyl) -lH-pyrazol-5-yl] mixed with nitric acid.