DE4437930A1 - 2-chloro-N- [1- (2,6-dichloro-4-difluoromethylphenyl) -1H-pyrazol-5-yl] propanamide - Google Patents

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-pyrazo l-5-yl]-propanamide of formula (II).

Description

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

It is known that certain arylpyrazoles as herbicides or as intermediate pro products for the production of herbicides can be used (cf. EP-A 303 153). That be as an intermediate for the preparation of the herbicide particularly interesting compound 2-chloro-N- [1- (2,6-dichloro-4-difluoromethyl-phe nyl) -4-nitro-1H-pyrazol-5-yl] propanamide 2-chloro-N- [1- (2,6-di Chlor-4-difluoromethyl-phenyl) -1H-pyrazol-5-yl] propanamide has not yet been used known from the literature.

The new compound 2-chloro-N- [1- (2,6-dichloro-4-difluoromethyl phenyl) -1H-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 (1) in very good Yield and high purity are obtained if the Ver bond 3- [2- (2,6-dichloro-4-trifluoromethylphenyl) hydrazino] propane nitrile 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) -1H-pyrazol-5-amine of the formula (III)

isolated and in a second stage with 2-chloropropionyl chloride, if appropriate in the presence of an acid acceptor and optionally in the presence of a ver reacts at temperatures between -20 ° C and + 100 ° C.

Surprisingly, the new Ver Binding of the formula (I) in significantly higher yield than in analog known Methodology performed synthesis (see. EP-A 303153) can be obtained. That he The method according to the invention thus represents a valuable addition to the stand of technology.

The course of the reaction in the process of the present invention can be as follows Formula scheme are reproduced:

The Ver to be used as starting material in the process according to the invention bond 3- [2- (2,6-dichloro-4-trifluoromethylphenyl) hydrazino] propane nitrile Formula (II) is known and can be prepared by a known method (see EP-A 303153).

In the first stage, the process according to the invention is preferably carried out in counter were carried out on a suitable base. As such, all the usual ones arrive organic or organic bases in question. These include, for example, alkali metal or alkaline earth metal hydrides, hydroxides, amides, alcoholates, acetates, carbonates or bicarbonates, such as lithium, sodium, Potassium or calcium hydride, lithium, sodium or potassium amide, sodium or potassium methylate, sodium or potassium ethylate, sodium or potassium propylate, aluminum isopropoxide, 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 bicarbonate, as well as basic organic nitrogen bonds, such as trimethylamine, triethylamine, tripropylamine, tributylamine, ethyl diisopropylamine, N, N-dimethylcydohexylamine, dicyclohexylamine, ethyl dicyclo hexylamine, N, N-dimethylaniline, N, N-dimethylbenzylamine, 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-dimethyl aminopyridine, diazabicyclooctane (DABCO), diazabicyclonones (DBN) or Di azabicycloundecen (DBU).

Alkali metal hydroxides, such as. B. sodium hydroxide or potassium hydroxide, or Alkali metal alcoholates, such as. B. sodium or potassium methanolate, ethanolate, -n- or -i-propanolate, -n-, -i-, -s- or -t-butanolate, -n-, -i-, -s- or -t-pentanolate,  are to be used in the process according to the invention in the first stage Bases particularly preferred.

As a diluent for carrying out the first stage of the invention The usual organic solvents are suitable for the process. For this include in particular aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as 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, di ethylene glycol dimethyl ether or diethyl ether; Ketones; such as acetone, butanone or Methyl isobutyl ketone; Nitriles, such as acetonitrile, propionitrile, or butyronitrile Benzonitrile; Amides, such as N, N-dimethylformamide, N, N-dimethylacetamide, N- Methyl formanilide, N-methyl-pyrrolidone or hexamethylphosphoric 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 such as B. methanol, ethanol, n- or i-propanol are used as Ver thinning agent in the implementation of the first stage of the invention driving particularly preferred.

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

The reaction temperatures can be carried out when carrying out the first stage of the process according to the invention can be varied over a wide range. Generally I think you work at 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 described in Normal pressure carried out. However, it is also possible to increase or decrease reduced pressure - generally between 0.1 bar and 10 bar.

To carry out the first stage of the process according to the invention, per mole of 3- [2- (2,6-dichloro-4-trifluoromethylphenyl) hydrazino] propane nitrile Formula (II) of formula (II) generally 1.0 to 5.0 moles, preferably 1.5 to 2.5 moles of a base.

In a preferred embodiment of the first stage of the invention Process, the starting compound of formula (II) in a suitable Ver submitted fertilizer and the air present in the reaction vessel then - preferably at an elevated temperature - replaced by an inert gas. Then it will be a base - preferably in a diluent such as water or one of the Dissolved alcohols and preferably before adding with a Inert gas treated - metered in and the reaction mixture is until the end of Reaction stirred under an inert gas atmosphere at the required temperature.

Processing for isolation of the product of the first stage - the connection of formula (III) - can be carried out in the usual way. For example is diluted with water to 2 to 5 times the volume and after a long time Stirring with cooling, the crystalline product is suctioned off isolated. It can be recrystallized, for example from xylene / cyclohexane, to be cleaned further.

The second stage of the process according to the invention is preferably carried out in counter a suitable acid acceptor was carried out. As such, everyone comes over Lichen inorganic or organic bases in question. These include, for example wise alkali metal or alkaline earth metal hydrides, hydroxides, amides, alcoholates, acetates, carbonates or bicarbonates, 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 butylate, 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, as well as basic organic nitrogen compounds, such as trimethylamine, triethylamine, tripropyl amine, tributylamine, ethyl-diisopropylamine, N, N-dimethylcyclohexylamine, di cyclohexylamine, ethyl dicydohexylamine, 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), di azabicyclonones (DBN) or diazabicycloundecene (DBU).

Pyridine is particularly preferred as an acid acceptor.

As a diluent for performing the second stage of the Invention The usual organic solvents are suitable for the process. These include in particular aliphatic, alicyclic or aromatic, counter optionally halogenated hydrocarbons, such as pentane, hexane, Heptane, petroleum ether, ligroin, gasoline, benzene, toluene, xylene, chlorobenzene, dichlor benzene, cyclohexane, methylcyclohexane, dichloromethane, chloroform, tetrachlor methane; 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, or butyronitrile Benzonitrile; Amides, such as N, N-dimethylformamide, N, N-dimethylacetamide, N- Methyl formanilide, N-methyl-pyrrolidone or hexamethylphosphoric triamide; Esters such as methyl acetate, ethyl ester, n- or -i-propyl ester, -n-, -i- or -s-butyl ester, sulfoxides, such as dimethyl sulfoxide.

The reaction temperatures can be carried out when carrying out the second stage of the process according to the invention can be varied over a wide range. Generally mine work at 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 described in Normal pressure carried out. However, it is also possible to increase or decrease reduced pressure - generally between 0.1 bar and 10 bar.  

To carry out the second stage of the process according to the invention, per mole of 1- (2,6-dichloro-4-difluoromethyl-phenyl) -1H-pyrazol-5-amine of the formula (III) generally 1.0 to 1.5 moles, preferably 1.05 to 1.2 moles of 2-chlorine propionic acid chloride.

In a preferred embodiment of the second stage of the invention The method of compound of formula (III) in a suitable Ver submitted fertilizer and added an acid acceptor. Then the 2- Chlor-propionic acid chloride slowly metered in and the reaction mixture until Stirred at the end of the implementation.

Processing for isolation of the second stage product - the connection of formula (I) - can be carried out in a conventional manner. For example diluted with water to 2 to 5 times the volume and after long stirring the crystalline product is isolated by suction.

The compound of the Formula (I) can be used as a starting material for the preparation of the herbicidally active compound 2-Chloro-N- [1- (2,6-dichloro-4-difluoromethylphenyl) -4-nitro-1H-pyrazol-5-yl] - propanamide (cf. EP-A 303153) used according to the following formula will:

Manufacturing examples step 1

10.3 g (34.5 mmol) of 3- [2- (2,6-dichloro-4-trifluoromethylphenyl) hydrazino] propane nitrile is dissolved in 20 ml of ethanol and refluxed for 15 minutes Boiling heated, the air in the reaction vessel by introducing nitrogen is ousted. With further introduction of nitrogen, the solution is brought to 20 ° C cooled and then ge with nitrogen over 20 minutes saturated solution of 5.9 g of 45% aqueous sodium hydroxide solution (66 mmol NaOH) dosed. With continuous introduction of nitrogen, the reaction mixture Boil under reflux for about 60 minutes and ge for another 20 hours at about 20 ° C stirs. Then the mixture is poured onto 85 ml of water and added for 2 hours 10 ° C stirred. The product that is obtained in crystalline form is filtered off with suction isolated, dried and recrystallized from 40 ml xylene / cyclohexane (Vol.:1: 1).

7.7 g (content: 99.6%, i.e. yield: 80% of theory) of 1- (2,6-dichloro- 4-difluoromethyl-phenyl) -1H-pyrazol-5-amine, melting point: 111 ° C.  

Level 2

9.6 g (34.8 mmol) of 1- (2,6-dichloro-4-difluoromethyl-phenyl) -1H-pyrazol-5-amine are placed in 40 ml of acetonitrile and mixed with 3.44 g of pyridine at 20 ° C. Then 4.8 g (37.0 mmol) of 2-chloropropionic acid chloride at 15 ° C to 20 ° C. added dropwise with stirring, the reaction mixture at 12 hours Stirred at 20 ° C and then poured onto 100 ml of ice water. After three hours Stirring, the crystalline product is isolated by suction and ge dries.

11.3 g (content: 96.7%, i.e. yield: 88% of theory) of 2-chloro-N- [1- (2,6-dichloro-4-difluoromethyl-phenyl) -1H-pyrazol-5-yl] propanamide from the enamel point 87 ° C.  

Conversion example

11.2 g (30.6 mmol) 2-chloro-N- [1- (2,6-dichloro-4-difluoromethyl-phenyl) -1H- pyrazol-5-yl] propanamide are placed in 40 ml of acetic acid and at 10 ° C to 15 ° C with 3.75 ml (39 mmol) of acetic anhydride. Then 1.6 ml (38 mmol) nitric acid (100%) at 10 ° C to 15 ° C with stirring dropwise added, the reaction mixture stirred at about 20 ° C for 20 hours and on finally added to 100 ml of water. After stirring for two hours, it will crystalline product isolated by suction and dried.

11.3 g (content: 88%, i.e. yield: 79% of theory) of 2-chloro-N- [1- (2,6-dichloro-4-difluoromethylphenyl) -4-nitro-1H-pyrazol-5-yl] propane amide from Melting point 113 ° C.

Claims (6)

1. 2-chloro-N- [1- (2,6-dichloro-4-difluoromethylphenyl) 1H-pyrazol-5-yl] propane amide of the formula (I) 2. Process for the preparation of 2-chloro-N- [1- (2,6-dichloro-4-difluoromethylphenyl) -1H-pyrazol-5-yl] propanamide of the formula (I) characterized in that when in a first stage 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) -1H-pyrazole-5-amine 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. 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 characterized in that this is done in the first stage at temperatures between 10 ° C and 120 ° C and in their second stage at temperatures between 0 ° C and + 100 ° C. 4. 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 characterized in that the first and second stages under normal pressure carries out. 5. 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 characterized in that the first stage is carried out under inert gas. 6. A process for the preparation of 2-chloro-N- [1- (2,6-dichloro-4-difluoromethylphenyl) -1H-pyrazol-5-yl] propanamide according to claim 2, characterized in that in the first Step per mole of 3- [2- (2,6-dichloro-4-trifluoromethylphenyl) hydrazino] propane nitrile of the formula (II) 1.0 to 5.0 mol of base are used and in the second stage per mol of 1- (2,6-dichloro-4-difluoromethylphenyl) -1H-pyrazol-5-amine of the formula (III) 1.0 to 1.5 mol of 2-chloropropionic acid chloride is used.