Process for the preparation of substituted phenyl hydrazines

The invention relates to a new process for the preparation of substituted phenylhydrazines which can be used as intermediates for the synthesis of herbicidal active compounds.

It is already known that substituted phenylhydrazines are obtained if substituted anilines are first diazotized with sodium nitrite in the presence of an acid and then reduced in a second stage, for example with tin (II) chloride, also in the presence of an acid (cf. e.g. Houben -Weyl, “Methods of Organic Chemistry”, Volume X, 2; page 203, Thieme Verlag Stuttgart 1967).

The disadvantage of this process is the often unsatisfactory yield and purity of the reaction products which can be obtained in this way, a fact which is based on the one hand in the general disadvantages of a multi-stage reaction procedure and on the other hand also due to special problems in both stages. For example, the diazonium salts (1. Stage), if anilines with hydrophobic substituents are used as starting compounds, often only poorly in the required aqueous medium. Another difficulty with diazotization is that side reactions such as azo coupling are possible and also occur. The reduction of the diazonium salts (2nd stage) is often not completely successful, which also contributes to contamination and reduced yield.

It has been found that substituted phenylhydrazines of the formula (I)<chemistry id="chem0001" num="0001"><img file="EP0187285B1_D0001.tif" /></chemistry>in which<ul id="ul0001" list-style="none"><li>R¹ and R² represent hydrogen or chlorine,</li><li>_R³ represents haloalkyl,</li><li>X represents oxygen, sulfur, sulfinyl or sulfonyl and</li><li>n stands for a number 0 or 1, is obtained if substituted chlorobenzenes of the formula (11)<chemistry id="chem0002" num="0002"><img file="EP0187285B1_D0002.tif" /></chemistry>in which</li><li>R¹, R², R³, X and n have the meanings given above, with hydrazine or hydrazine hydrate in the presence of a diluent and, if appropriate, at elevated pressure at temperatures between 60 ° C. and 160 ° C.</li></ul>

It is to be regarded as extremely surprising that the desired substituted phenylhydrazines are obtained in high yields and good purity with the aid of the process according to the invention, since it was not to be expected according to the prior art that the at least three chlorine atoms present in the starting product of the formula ( II) are available for the substitution reaction according to the invention, selectively only one product is formed.

The method according to the invention has a number of advantages. This includes, for example, the one-step reaction in an organic solvent, which avoids solubility problems when using hydrophobic starting materials. The costly isolation of intermediate products is also avoided. Another advantage of the process according to the invention is the easy accessibility of the substituted chlorobenzenes of the formula (11) which are suitable as starting compounds.

With the aid of the process according to the invention, preference is given to obtaining those substituted phenylhydrazines of the formula (I) in which<ul id="ul0002" list-style="none"><li>R¹ and R² represent hydrogen or chlorine,</li><li>X represents oxygen, sulfur, sulfinyl or sulfonyl,</li><li>R³ represents straight-chain or branched haloalkyl having 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms and</li><li>n stands for a number 0 or 1.</li></ul>

Compounds of the formula (I) in which<ul id="ul0003" list-style="none"><li>R¹ and R² represent hydrogen or chlorine,</li><li>R³represent difluoromethyl, trifluoromethyl, trichloromethyl, dichlorofluoromethyl, difluorochloromethyl, trifluoroethyl, tetrafluoroethyl, pentafluoroethyl, tetrafluorochloroethyl, trifluorochloroethyl, trifluorodichloroethyl, difluorotrichloroethyl, difluorotrichloroethyl, difluorachichloroethyl, difluorachichloroethyl, difluorodichloroethyl</li><li>X represents sulfur, sulfinyl or sulfonyl and</li><li>n stands for a number 0 or 1.</li></ul>

If, for example, 1,2,3-trichloro-5-trifluoromethylbenzene and hydrazine hydrate are used as starting materials, the course of the reaction of the process according to the invention can be represented by the following formula:<chemistry id="chem0003" num="0003"><img file="EP0187285B1_D0003.tif" /></chemistry>

Formula (11) provides a general definition of the substituted chlorobenzenes required as starting materials for carrying out the process according to the invention.

Compounds of the formula (II) in which R¹, R², R³, X and n represent those radicals which have already been mentioned as preferred for these substituents and indices in connection with the description of the end products of the formula (I).

The substituted chlorobenzenes of the formula (11) are known (cf., for example, DE-OS 2,644,641; DE-OS 2,333,848; JP 49/2108; J. Fluorine Chem. 9, 113-126 (1977); Ind. Eng. Chem. 39, 378-380 (1947)) or can be prepared in an analogous manner by processes known in principle. The process according to the invention can optionally be carried out in the presence of a suitable diluent. The process according to the invention is preferably carried out using diluents.

Practically all inert organic solvents can be used as diluents. These include, in particular, polar or dipolar aprotic solvents such as alcohols, for example methanol, ethanol, n- or i-propanol, ethylene glycol, or ethers, such as dioxane, dimethoxyethane, diethylene glycol dimethyl ether, or sulfoxides, such as dimethyl sulfoxide. Particularly preferred diluents are dioxane and n-propanol.

Weakly basic solvents such as pyridine are also particularly preferred as diluents.

The process according to the invention is generally carried out at temperatures between + 60 ° C and + 160 ° C. The temperature range between + 80 ° C and + 140 ° C, in particular between + 100 ° C and 120 ° C, is preferred. The reactions are generally carried out under normal pressure. Depending on the boiling point of the diluent used, however, it may also be advantageous to apply the pressure required to achieve the required reaction temperature. In these cases, the pressure range is generally from 1 to 30 bar, preferably from 1 to 20 bar.

To carry out the process according to the invention, 1.0 to 10.0 mol, preferably 2.0 to 8.0 mol, in particular 3.0 to 7.0 mol, of hydrazine or are generally employed per mol of substituted chlorobenzene of the formula (II) Hydrazine hydrate.

The reaction is carried out in such a way that the reactants, dissolved in the appropriate diluent, are heated to the required reaction temperature for 8 to 60 hours (the course of the reaction can be monitored, for example, by gas chromatography), with the use of low-boiling diluents, where appropriate, under pressure. so that the required reaction temperature is reached.

For working up, the solvent is distilled off, the residue is taken up in water, the mixture is adjusted to pH 10 with aqueous sodium hydroxide solution and the product is extracted with a water-immiscible solvent. The combined organic phases are optionally washed again with concentrated aqueous sodium chloride solution, dried and concentrated in vacuo.

The crude products of the formula (I) obtained in this way can either be purified by distillation or crystallized from a suitable solvent, such as, for example, n-hexane.

The substituted phenylhydrazines of the formula (I) are valuable intermediates and are suitable, for example, for the synthesis of herbicidally active 5-acylamino-1-phenylpyrazoles, which are described, for example, in the previously unpublished patent applications DE-P 3 337 543 dated October 15, 1983 or DE- P 3 402 308 of January 24, 1984 or DE-P 3 420 985.9 of June 6, 1984.

This gives new 5-aminopyrazoles of the formula (III)<chemistry id="chem0004" num="0004"><img file="EP0187285B1_D0004.tif" /></chemistry>in which<ul id="ul0004" list-style="none"><li>R⁴ represents cyano or alkylaminocarbonyl and</li><li>R¹, R², R³, X and n have the meaning given above if acrylonitrile derivatives of the formula (IV)<chemistry id="chem0005" num="0005"><img file="EP0187285B1_D0005.tif" /></chemistry>in which</li><li>R4 has the meaning given above, with phenylhydrazines of the formula (I)<chemistry id="chem0006" num="0006"><img file="EP0187285B1_D0006.tif" /></chemistry>in which</li><li>R¹, R², R³, X and n have the meaning given above, either first in a first stage, if appropriate in the presence of a diluent, such as, for example, glacial acetic acid or ethanol, and, if appropriate, in the presence of a reaction auxiliary, such as, for example, sodium acetate, at temperatures between -20.degree. C. and + 20.degree. C. to give the phenylhydrazine derivatives of the formula (V)</li></ul><chemistry id="chem0007" num="0007"><img file="EP0187285B1_D0007.tif" /></chemistry>in which<ul id="ul0005" list-style="none"><li>_R', _R², _R³, R⁴, X and n have the meaning given above, and this in a second stage, optionally in the presence of a diluent such as ethylene glycol monoethyl ether, cyclized at temperatures between + 50 ° C and + 150 ° C, or directly in one reaction step without isolation of the intermediate Formula (V), optionally cyclized in the presence of a diluent such as, for example, ethylene glycol monoethyl ether or ethanol at temperatures between + 50 ° C. and + 150 ° C.</li></ul>

The acrylonitrile derivatives of the formula (IV) are known (cf. EP 34 945 or DE-OS 3 129 429).

New herbicidally active substituted 5-acylamino-1-phenylpyrazoles of the formula (VI) are obtained.<chemistry id="chem0008" num="0008"><img file="EP0187285B1_D0008.tif" /></chemistry>in which<ul id="ul0006" list-style="none"><li>_R¹, _R², _R³, R⁴, X and n have the meaning given above and</li><li>R⁵ represents hydrogen, alkyl, alkenyl, alkynyl, optionally substituted cycloalkyl, alkoxyalkyl, alkylthioalkyl, haloalkyl or optionally substituted aryl when 5-aminopyrazoles of the formula (III)<chemistry id="chem0009" num="0009"><img file="EP0187285B1_D0009.tif" /></chemistry>in which</li><li>R¹, R², R³, R⁴, X and n have the meaning given above, with acylating agents of the formula (VII)<chemistry id="chem0010" num="0010"><img file="EP0187285B1_D0010.tif" /></chemistry>in which</li><li>R⁵ has the meaning given above and</li></ul>

A stands for an activating leaving group such as halogen or for a radical R.^5-Stands CO-O, where R⁵ has the meaning given above, optionally in the presence of a diluent such as. B. chloroform and optionally in the presence of an acid binder such as triethylamine at temperatures between -20 and + 150 ° C.

To carry out this process, 1 to 20 mol, preferably 1 to 15 mol, of acylating agent of the formula (VII) and generally 1 to 3 mol, preferably 1 to 2 mol, of acid binder are generally employed per mol of 5-aminopyrazole of the formula (III) a. The reaction, work-up and isolation of the end products of the formula (VI) is carried out in a customary manner. The acylating agents of the formula (VII) are generally known.

Manufacturing examples

example 1

<chemistry id="chem0011" num="0011"><img file="EP0187285B1_D0011.tif" /></chemistry>6.2 g (0.025 mol) of 3,4,5-trichlorotrifluoromethylbenzene and 6.25 g (0.125 mol) of hydrazine hydrate are refluxed in 12 ml of pyridine at 115-120 ° C. for 48 hours. For working up, the solvent is distilled off, the residue is taken up in water and extracted three times with in each case about 30 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate, concentrated in vacuo and then distilled.

5.1 g (83% of theory) of 2,6-di-chloro-4-trifluoromethylphenylhydrazine with a melting point of 56 to 57 ° C. and a content of 90% determined by gas chromatography are obtained.

Example 2

<chemistry id="chem0012" num="0012"><img file="EP0187285B1_D0012.tif" /></chemistry>200 g (0.704 mol) of 2,3,4,5-tetrachlorotrifluoromethylbenzene and 240 ml (247.2 g / 4.94 mol) of hydrazine hydrate in 500 ml of dioxane are heated under reflux at 100-105 ° C. for 14 hours. The heavy (aqueous) phase is separated from the cooled two-phase reaction mixture and the organic phase is concentrated to dryness in vacuo. The residue is suspended in 600 ml of water and 100 ml of dichloromethane, adjusted to pH 10 with 10% aqueous sodium hydroxide solution and slowly warmed to 30 ° C. to 35 ° C., two clear phases forming from the cloudy suspension. The mixture is allowed to cool to room temperature, the organic phase is separated off, washed with 200 ml of concentrated aqueous sodium chloride solution, dried over magnesium sulfate and the solvent is removed in vacuo. The crude product is stirred in 370 ml of boiling hexane for 3 to 4 hours, then cooled for 15 hours at 0 ° C. to 5 ° C., suction filtered cold and dried in vacuo at 50 ° C. for 2 to 3 hours.

146 g (71.2% of theory) of 2,3,6-trichloro-4-trifluoromethyl-phenylhydrazine with a melting point of 67 to 70 ° C. and a content of 96% determined by gas chromatography are obtained.

Example 3

<chemistry id="chem0013" num="0013"><img file="EP0187285B1_D0013.tif" /></chemistry>

85 g (0.27 mol) of 1,2,3-trichloro-5-trifluoromethylsulfonylbenzene in 68 ml are added dropwise to 41 g (0.82 mol) of hydrazine hydrate in 136 ml of dioxane at 20 ° C. to 40 ° C. with stirring Dioxane. When the addition is complete, the mixture is stirred at 100-105 ° C. under reflux for 2 hours. After cooling, the reaction mixture is mixed with water and the precipitate formed is filtered off with suction. After drying, the product is recrystallized from toluene.

68 g (81% of theory) of 2,6-dichloro-4-trifluoromethylsulfonylphenylhydrazine with a melting point of 135 to 137 ° C. are obtained.

The following substituted phenylhydrazines of the formula (I) can be obtained in a corresponding manner and in accordance with the general preparation instructions:<chemistry id="chem0014" num="0014"><img file="EP0187285B1_D0014.tif" /></chemistry><tables id="tabl0001" num="0001"><img file="EP0187285B1_D0015.tif" /></tables>Preparation of the starting compound<chemistry id="chem0015" num="0015"><img file="EP0187285B1_D0016.tif" /></chemistry>

A mixture of 1123 g (4.6 mol) of 4-trifluoromethylsulfonylchlorobenzene, 11.5 g (0.13 mol) of iron (II) sulfide and 11.5 g (0.045 mol) of iodine are added at 100 ° C. to 120 ° C. Chlorine added. The reaction is followed by gas chromatography and terminated at a 36% content of the desired product. The mixture is worked up by fractional distillation.

554 g (38.5% of theory) of 3,4,5-trichlorotrifluoromethylsulfonylbenzene are obtained from the boiling point 143 ° C. at 22 mbar and from the melting point 102 ° C. to 103 ° C.

Production example for a herbicidally active compound:<chemistry id="chem0016" num="0016"><img file="EP0187285B1_D0017.tif" /></chemistry>

A suspension of 3.5 g (0.01 mol) of 5-amino-4-cyano-1- (2,6-dichloro-4-trifluoromethylthiophenyl) pyrazole in 30 ml of chloroform are stirred with 0 ° C first mixed with 10 ml (0.11 mol) of propionyl chloride and then with 1.8 ml (0.02 mol) of pyridine in 15 ml of chloroform. A clear solution is obtained which, after the addition has ended, is stirred for a further 20 hours at room temperature. The solution thus obtained is evaporated to dryness. For working up, the mixture is taken up in 50 ml of ethanol, aqueous ammonia is added until the reaction is alkaline, the mixture is heated under reflux for 10 minutes, the volatile constituents are removed in vacuo, the residue is taken up in 100 ml of chloroform, washed with water and then with 2N aqueous hydrochloric acid and again with water, dried over sodium sulfate and removed the solvent in vacuo. 3.4 g (83% of theory) of 5-propionylamino-4-cyano-1- (2,6-dichloro-4-trifluoromethylthiophenyl) pyrazole of melting point 153 to 156 ° C. are obtained.

Preparation of the starting compounds

<chemistry id="chem0017" num="0017"><img file="EP0187285B1_D0018.tif" /></chemistry>

To a suspension of 13.9 g (0.05 mol) of (2,6-dichloro-4-trifluoromethylthio) phenylhydrazine and 2.1 g (0.025 mol) of sodium acetate in 25 ml of glacial acetic acid, 6.1 g ( 0.05 mol) ethoxymethylene malononitrile. When the addition has ended, the mixture is stirred for a further hour at room temperature and the solid obtained is filtered off, which is washed successively with water, aqueous sodium hydrogen carbonate solution and again with water and then dried. 15.8 g (89% of theory) of 1- (2,2-dicyanethen-1-yl) -2- (2,6-dichloro-4-trifluoromethylthiophenyl) hydrazine with a melting point of 160 ° C. are obtained.<chemistry id="chem0018" num="0018"><img file="EP0187285B1_D0019.tif" /></chemistry>

14.1 g (0.04 mol) of 1- (2,2-dicyanethen-1-yl) -2- (2,6-dichloro-4-trifluoromethylthio-phenyl) hydrazine in 30 ml of ethylene glycol monoethyl ether are refluxed for 2 hours heated. The hot solution is mixed with activated carbon, filtered and diluted with 60 ml of water. The precipitate is filtered off and dried. 9.8 g (70% of theory) of 5-amino-4-cyano-1- (2,6-dichloro-4-trifluoromethylthiophenyl) pyrazole of melting point 185 to 187 ° C. are obtained.

Application example

In the following application example, the compound listed below is used as a reference substance:<chemistry id="chem0019" num="0019"><img file="EP0187285B1_D0020.tif" /></chemistry>

4-cyano-5-propionylamino-1- (2,4,6-trichlorophenyl) pyrazole (known from DE-OS 3 226 513).

Example A

Pre-emergence test Solvent: 5 parts by weight of acetone emulsifier: 1 part by weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, the stated amount of emulsifier is added and the concentrate is diluted with water to the desired concentration.

Seeds of the test plants are sown in normal soil and watered with the preparation of active compound after 24 hours. The amount of water per unit area is expediently kept constant. The concentration of active substance in the preparation is irrelevant, the only decisive factor is the amount of active substance applied per unit area. After three weeks, the degree of damage to the plants is rated in% damage compared to the development of the untreated control. It means:<ul id="ul0007" list-style="none"><li>0% = no effect (like untreated control)</li><li>100% = total annihilation</li></ul>

In this example, for example, the compound according to preparation example (VI-1) shows a clear superiority in herbicidal activity as well as in crop selectivity compared to the prior art; this applies in particular to wheat.