RU2236399C2 - Methods for preparing compounds of ortho-nitrobenzonitrile (variants) - Google Patents

Abstract

FIELD: organic chemistry, chemical technology, pesticides.

SUBSTANCE: invention relates to new methods (variants) for preparing intermediate compounds, in particular, 4-cyano-3-nitrobenzofluoride, that can be used in preparing pesticides. Invention relates also to methods for preparing compound of the formula (I):

wherein R¹ means (C₁-C₄)-halogenalkyl; R² means hydrogen atom, (C₁-C₄)-alkoxy-group. Methods involve interaction of the corresponding ortho-nitrohalogenbenzene of the formula (II):

wherein R¹ and R² have values indicated above; X represents fluorine or bromine atom: with (a) alkaline metal cyanide in anhydrous solvent being optionally in the presence of a catalyst in the case when X means fluorine atom; or (b) with alkaline metal cyanide in the presence of catalytic amount of copper (I) cyanide and interphase catalyst in the case when X means bromine atom, or interaction of the corresponding ortho-nitrohalogenbenzene of the formula (II) with copper (I) cyanide being optionally in the presence of catalyst taken among alkaline or alkaline-earth metal bromide. Method provides preparing compound of ortho-nitrobenzonitrile with high yield and/or high selectivity.

EFFECT: improved preparing methods.

19 cl, 14 tbl, 12 ex

Description

This invention relates to new methods for producing intermediate compounds (in particular, 4-cyano-3-nitrobenzotrifluoride), which can be used to obtain pesticides.

Pesticidal 4-benzoylisoxazoles, in particular 5-cyclopropylisoxazole herbicides and intermediates in their synthesis, are described in the literature, for example, in European Patent Publications Nos. 0418175, 0487353, 0527036, 0560482, 0609798 and 0682659.

Various methods are known for preparing these compounds. This invention is directed to the development of improved methods for producing pesticides and intermediates that can be used in their preparation.

Therefore, the aim of this invention is to develop new and more economical methods for producing compounds of ortho-nitrobenzonitrile.

The next objective of this invention is to develop methods for producing ortho-nitrobenzonitrile compounds with high yield and / or high selectivity.

A further object of the present invention is to provide a process for preparing ortho-nitrobenzonitrile compounds requiring the use of a small amount of copper compound as a catalyst.

Another objective of this invention is to develop a method for producing compounds of ortho-nitrobenzonitrile, including the use of copper cyanide (I) without the need for a catalyst.

The next objective of this invention is to develop a method for producing compounds of ortho-nitrobenzonitrile, carried out at a lower temperature than the known methods, and therefore easier to implement.

The present invention allows to achieve these goals in whole or in part.

SUMMARY OF THE INVENTION

The present invention accordingly provides a method for producing an ortho-nitrobenzonitrile compound of the formula (I):

where R ¹ is C _1-4 haloalkyl (preferably trifluoromethyl), fluoro, chloro or bromo;

R ² is hydrogen or C _1-4 alkoxy;

comprising the reaction of the corresponding ortho-nitrogalobenzene formula (II):

where R ¹ and R ² have the above meanings, and X is a fluorine, chlorine or bromine atom, s, when X is a fluorine atom:

(a) an alkali metal cyanide in an anhydrous solvent, optionally in the presence of a catalyst; or

when X is a chlorine atom:

(b) copper cyanide (I) and a source of bromide selected from hydrogen bromide, bromide and tetraalkylammonium bromide; optionally in the presence of an alkali or alkaline earth metal bromide; or

(c) an alkali metal or tetraalkylammonium cyanide in the presence of copper (I) bromide and an interphase catalyst; or

(d) copper cyanide (I) and lithium iodide; or

when X is a bromine atom:

(e) copper cyanide (I) optionally in the presence of a catalyst selected from alkali metal or alkaline earth metal bromide;

or

(f) an alkali metal cyanide in the presence of a catalytic amount of copper (I) cyanide and an interfacial catalyst.

Some compounds of formula (I) are known, and many methods for their preparation and conversion to herbicidal derivatives of 4-benzoylisoxazole are described in the above European patent applications.

The compounds of formula (II) are known or can be obtained by known methods.

In formulas (I) and (II), as well as in the formulas below, the symbols preferably have the following meanings:

R ^{1 is} preferably trifluoromethyl, fluoro or bromo; a R ² is hydrogen or methoxy.

In a particularly preferred embodiment of the invention, R ¹ is trifluoromethyl and R ² is hydrogen.

In accordance with this invention, the term "alkyl", which is part of the tetraalkylammonium salts, is intended to mean a straight or branched chain alkyl group containing from 1 to 6 carbon atoms.

DETAILED DESCRIPTION OF THE INVENTION

The above preparation (a) of compounds of formula (I) from compounds of formula (II), where X is a fluorine atom, is carried out using alkali metal cyanide (for example, sodium or potassium cyanide). Sodium cyanide is preferred. The amount of cyanide used is usually 1-2 molar equivalents, preferably 1-1.1 molar equivalents.

Many anhydrous solvents are suitable, for example nitriles, such as acetonitrile or benzonitrile; ethers such as tetrahydrofuran or diglyme (diethylene glycol dimethyl ether); amides, such as N, N-dimethylformamide or N-methylpyrrolidone; ketones such as methyl isobutyl ketone; esters such as methyl benzoate or n-butyl acetate; dimethyl sulfoxide or sulfolane. The solvent is preferably selected from benzonitrile, acetonitrile, tetrahydrofuran or N, N-dimethylformamide.

The reaction is usually carried out in a solvent containing less than about 1 vol.% Water, preferably less than about 0.5%, even more preferably less than about 0.1%, usually from about 0.005 to 0.05%. However, it should be borne in mind that in some cases a slightly higher or lower water content is allowed depending on the nature of the solvent used and the reaction temperature, the resulting compound of formula (I) and other reaction conditions.

Preferably, a catalyst is used which can be selected from ammonium salts (such as chlorides, bromides or tetraalkylammonium or trialkylbenzylammonium hydrosulphates, in which the alkyl groups have straight or branched chains containing from 1 to 6 carbon atoms, such as tetramethylammonium bromide); or preferably guanidinium salts (such as hexabutylguanidinium chloride or hexamethylguanidinium chloride). When using a catalyst, its amount is usually from 0.01 to 0.3 molar equivalents, preferably from 0.05 to 0.25 molar equivalents.

The reaction temperature is usually from 20 ° C to the boiling point of the solvent, preferably from 30 to 180 ° C, more preferably from 60 to 100 ° C.

The above preparation (b) of compounds of formula (I) from compounds of formula (II), where X is a chlorine atom, is carried out using copper (I) cyanide and a bromide source selected from hydrogen bromide, bromide and tetraalkylammonium bromide, optionally in the presence of alkaline bromide or an alkaline earth metal, preferably lithium bromide. According to this method, the amount of copper cyanide used is usually 0.5-2 molar equivalents, preferably 0.8-1.2 molar equivalents.

The amount of bromide source is usually 0.05-1 molar equivalent.

If alkali metal or alkaline earth metal bromide is also present in the reaction mixture, its amount is catalytic and is usually 0.01-0.5 molar equivalents, usually 0.02-0.05 molar equivalents.

The solvent may be selected from nitriles, such as acetonitrile or benzonitrile; ketones such as methyl isobutyl ketone; ethers such as tetrahydrofuran or diglyme (diethylene glycol dimethyl ether); esters such as methyl benzoate or n-butyl acetate; dimethyl sulfoxide or sulfolane. Preferred solvents are acetonitrile, benzonitrile or diglyme.

The concentration of the compound of formula (II) used in the reaction solvent is usually from 0.1 to 2 ml / mmol, preferably from 0.2 to 1 ml / mmol.

The reaction temperature is usually from 100 to 200 ° C., Preferably from 130 to 180 ° C.

The above preparation (c) of compounds of formula (I) from compounds of formula (II), where X is a chlorine atom, is carried out using alkali metal cyanide (e.g. sodium or potassium cyanide) or tetraalkylammonium cyanide in the presence of copper (I) bromide and an interphase catalyst .

The alkali metal cyanide is preferably potassium cyanide. The amount of alkali metal cyanide or tetraalkylammonium used is usually 1-1.5 molar equivalents (preferably 1-1.1 molar equivalents). The amount of copper (I) bromide used is usually from 0.01 to 2 molar equivalents (preferably 1 molar equivalent). The reaction is carried out using a solid or liquid interfacial catalyst. The interfacial catalyst may be selected from tetraalkylammonium or trialkylbenzylammonium salts (such as tetramethylammonium bromide or benzyltrimethylammonium bromide); phosphonium salts (such as tributylhexadecylphosphonium bromide); guanidinium salts (such as hexabutylguanidinium bromide or hexamethylguanidinium bromide); and crown ethers (such as 18-crown-6). The amount of phase transfer catalyst used is typically 0.05-0.3 molar equivalents. Suitable reaction solvents include nitriles, such as acetonitrile or benzonitrile; ethers such as tetrahydrofuran or diglyme (diethylene glycol dimethyl ether); ketones such as methyl isobutyl ketone; or esters, such as methyl benzoate. A preferred solvent is acetonitrile.

The concentration of the compound of formula (II) used in the reaction solvent is usually from 0.1 to 2 ml / mmol, preferably from 0.2 to 1 ml / mmol.

The reaction temperature is usually from 100 to 200 ° C., Preferably from 130 to 180 ° C.

The above preparation (d) of compounds of formula (I) from compounds of formula (II), where X is a chlorine atom, is carried out using copper (I) cyanide and lithium iodide. Typically, 0.5-2 molar equivalents (preferably 0.8-1.2 molar equivalents) of copper (I) cyanide are used in the reaction. The amount of lithium iodide used is usually from 0.05 to 2 molar equivalents, preferably from 0.2 to 0.5 molar equivalents.

Suitable solvents for the reaction include nitriles, such as benzonitrile or acetonitrile; ethers such as diglyme (diethylene glycol dimethyl ether); ketones such as methyl isobutyl ketone; or esters, such as methyl benzoate.

The reaction temperature is usually from 100 to 200 ° C., Preferably from 130 to 180 ° C.

The above preparation (e) of compounds of formula (I) from compounds of formula (II), where X is a bromine atom, is carried out using copper (I) cyanide, optionally in the presence of a catalyst selected from alkali metal or alkaline earth metal bromide, preferably lithium bromide. Typically, 0.5-2 molar equivalents (preferably 1-1.1 molar equivalents) of copper (I) cyanide are used in the reaction. When using a catalyst, its amount is usually from 0.05 to 2 molar equivalents.

Suitable reaction solvents include nitriles, such as acetonitrile or benzonitrile; ethers such as tetrahydrofuran or diglyme (diethylene glycol dimethyl ether); ketones such as methyl isobutyl ketone; esters such as methyl benzoate or n-butyl acetate; amides, such as N, N-dimethylformamide or N-methylpyrrolidone; dimethyl sulfoxide or sulfolane. Preferred solvents are acetonitrile, benzonitrile or tetrahydrofuran.

The reaction temperature is usually from 100 to 200 ° C, preferably from 110 to 160 ° C (more preferably from 120 to 140 ° C).

The compound of formula (II) used in the reaction may contain a portion (usually up to 20%) of the corresponding compound in which the bromine atom is replaced by a chlorine atom. It was found that this does not harm the reaction. Therefore, it may be more convenient and simple to purify and isolate the nitrile compound of the formula (I) than to use the pure compound of the formula (II). Such isolation can be carried out using standard procedures known in the art, for example by distillation.

The above preparation (f) of compounds of formula (I) from compounds of formula (II), where X is a bromine atom, is carried out using an alkali metal cyanide in the presence of a catalytic amount of copper (I) cyanide and an interphase catalyst. A preferred alkali metal cyanide is potassium cyanide. The amount of copper (I) cyanide used is usually from 0.05 to 0.2 molar equivalents. The amount of alkali metal cyanide used is usually 0.5-2 molar equivalents, preferably 0.6-1.3 molar equivalents (more preferably 0.7-1 molar equivalents). The interfacial catalyst may be selected from alkali metal or alkaline earth metal bromides, preferably lithium bromide; tetraalkylammonium bromides or trialkylbenzylammonium bromides in which the alkyl groups have straight or branched chains containing from 1 to 6 carbon atoms (such as tetramethylammonium bromide or benzyltrimethylammonium bromide); phosphonium salts (such as tributylhexadecylphosphonium bromide); guanidinium salts (such as hexabutylguanidinium bromide or hexamethylguanidinium bromide); and crown ethers (such as 18-crown-6). The amount of interfacial catalyst used is usually 0.05-0.5 molar equivalents (preferably 0.05-0.3 molar equivalents).

Suitable reaction solvents include nitriles, such as acetonitrile or benzonitrile; alcohols such as n-butanol; amides, such as N, N-dimethylformamide or N-methylpyrrolidone; ketones such as methyl isobutyl ketone; esters such as methyl benzoate; ethers such as tetrahydrofuran or diglyme (diethylene glycol dimethyl ether); dimethyl sulfoxide or sulfolane.

The concentration of the compound of formula (II) used in the reaction solvent is usually from 0.1 to 2 ml / mmol, preferably from 0.2 to 1 ml / mmol, more preferably from 0.2 to 0.4 ml / mmol.

The reaction temperature is usually from 100 to 200 ° C., Preferably from 110 to 160 ° C.

In accordance with a further object of the present invention, a process (g) is provided for preparing a compound of formula (II), wherein R ¹ and R ² are as defined above and X is a bromine atom comprising the reaction of a corresponding compound of formula (II), where X is a chlorine atom, with a source of bromide.

Examples of suitable bromide sources include alkali metal bromides (such as potassium bromide or lithium); alkaline earth metal bromides (such as magnesium bromide); copper bromide (I); copper bromide (II); zinc bromide; hydrogen bromide; or bromine; or a mixture of lithium bromide and copper bromide (I). A preferred source of bromide is a mixture of lithium bromide and copper bromide (I); or magnesium bromide, or copper bromide (II). The amount of bromide source used is usually from 1 to 5 molar equivalents. When using a mixture of lithium bromide and copper bromide (I), 0.1-1 molar equivalents of copper bromide (I) are usually used together with one or two molar equivalents of lithium bromide.

A solvent is usually needed to get good results. Suitable reaction solvents include nitriles, such as acetonitrile or benzonitrile; ethers such as tetrahydrofuran or diglyme (diethylene glycol dimethyl ether); ketones such as methyl isobutyl ketone; esters such as methyl benzoate or n-butyl acetate; N-methylpyrrolidone; alkanoic acids such as acetic acid; dimethyl sulfoxide and sulfolane.

The reaction temperature is usually from 100 to 200 ° C., Preferably from 130 to 180 ° C. Good results can be obtained by implementing this method in a concentrated medium.

In accordance with another feature of the present invention, method (e) or (f) can be combined with method (g) to obtain a compound of formula (I) starting from a compound of formula (II), where X is a chlorine atom.

The compounds of formula (I) obtained by the methods in accordance with this invention can be used to obtain herbicidal active derivatives of 4-benzoylisoxazole, for example, according to the following reaction scheme:

4-Benzoylisoxazoles of the formula (III) are described, for example, in European Patent Publications Nos. 0418175, 0527036 and 0560482.

The invention is illustrated by the following non-limiting examples. The indicated concentrations of the ingredients in the solvent are intended to mean the concentration of the compound of formula (II) in the solvent (i.e., ml of solvent / mmol of the compound of formula (II)).

Example 1

Preparation of 4-cyano-3-nitrobenzotrifluoride from 4-fluoro-3-nitrobenzotrifluoride using alkali metal cyanide

(method (a)):

A mixture of 4-fluoro-3-nitrobenzotrifluoride (1 mmol) and sodium or potassium cyanide (1 mmol), as well as acetonitrile or benzonitrile (1 ml / mmol) is mixed at 20 ° C and heated for 6 hours at 80 ° C. getting the target product. The results are presented in table 1, from which it follows that the use of sodium cyanide provides good selectivity.

Example 2

Preparation of 4-cyano-3-nitrobenzotrifluoride from 4-fluoro-3-nitrobenzotrifluoride using sodium cyanide: action of temperature, solvent and catalyst (method (a)):

A mixture of 4-fluoro-3-nitrobenzotrifluoride (1 mmol) and sodium cyanide (1 mmol), as well as N, N-dimethylformamide, acetonitrile, tetrahydrofuran or benzonitrile (1 ml / mmol) is stirred at 20 ° C and heated for 6 hours, getting the target product. The results are presented in table 2, from which it follows that benzonitrile (PhCN) provides the highest selectivity.

The above experimental procedure is repeated at 80 ° C, but in the presence of a catalyst (0.2 equivalent) and acetonitrile, tetrahydrofuran or benzonitrile (1 ml / mmol). Hexabutylguanidinium chloride or tetrabutylammonium bromide are used as catalysts. The results presented in table 3 show that the use of hexabutylguanidinium chloride as a catalyst provides very good selectivity, especially with respect to tetrahydrofuran or benzonitrile.

(a) = hexabutylguanidinium chloride

(b) = tetrabutylammonium bromide

Example 3

Preparation of 4-cyano-3-nitrobenzotrifluoride from 4-chloro-3-nitrobenzotrifluoride using copper cyanide (I) and a bromide source (method (b)):

A mixture of 4-chloro-3-nitrobenzotrifluoride (1 or 1.3 equivalents), copper (I) cyanide (1 equivalent) and bromine (optionally in the presence of a catalytic amount of lithium bromide) or hydrogen bromide (47% aq.) Is stirred in benzonitrile ( 2 equivalents) at 20 ° C and subjected to heating at 170 ° C to obtain the desired product. The results are presented in table 4. The selectivity in these reactions is at least 90%

.

.

ClTNB = 4-chloro-3-nitrobenzotrifluoride.

The above procedure is repeated using 4-chloro-3-nitrobenzotrifluoride (1 equivalent), copper cyanide (I) (1 equivalent) and benzyltrimethylammonium bromide (1 equivalent) in acetonitrile (1 ml / mmol) with heating at 160 ° C for 6 hours and obtaining the target compound. The conversion of 4-chloro-3-nitrobenzotrifluoride is 94%, the product yield is 62%, and the selectivity is 66%.

The above experiment is repeated, but with the following changes: copper (I) cyanide (1 equivalent) and tert-butylamine hydrobromide (1 equivalent) in benzonitrile (2 equivalents) are mixed at 20 ° C and then heated to 150 ° C. After that, 4-chloro-3-nitrobenzotrifluoride (1.2 equivalents) was added over an hour and the mixture was kept at this temperature for 7 hours. It is obvious (table 5) that when using these conditions, the reaction proceeds with good selectivity.

Example 4

Preparation of 4-cyano-3-nitrobenzotrifluoride from 4-chloro-3-nitrobenzotrifluoride using alkali metal cyanide, copper bromide (I) and phase transfer catalyst (method (c)):

A mixture of 4-chloro-3-nitrobenzotrifluoride (1 equivalent), potassium cyanide (1 equivalent), copper bromide (I) (1 equivalent) and quaternary ammonium salt (0.2 equivalent) is mixed at 20 ° C, and then subjected to heating with acetonitrile (1 ml / mmol) at 160 ° C for 6 hours, obtaining the target product. Table 6 shows the results, from which it follows that such conditions provide good selectivity.

Example 5

Preparation of 4-cyano-3-nitrobenzotrifluoride from 4-chloro-3-nitrobenzotrifluoride using copper cyanide (I) and lithium iodide (process (d)):

A mixture of 4-chloro-3-nitrobenzotrifluoride (1 equivalent), copper cyanide (1 equivalent) and lithium iodide (0.2 or 0.5 equivalent) is heated with benzonitrile or diglyme (diethylene glycol dimethyl ether) (1 ml / mmol) for 6 hours at 160 ° C, obtaining the target product. Lithium iodide is selected because of its solubility in organic solvents. Table 7 shows the results, from which it follows that the use of 0.5 equivalent of lithium iodide is particularly good.

Example 6

Obtaining 4-cyano-3-nitrobenzotrifluoride from 4-bromo-3-nitrobenzotrifluoride using copper cyanide (I) optionally in the presence of lithium bromide (method (e)):

A mixture of 4-bromo-3-nitrobenzotrifluoride (1 equivalent) and copper cyanide (I) (1 equivalent), optionally in the presence of lithium bromide (1 equivalent) and benzonitrile or tetrahydrofuran (1 ml / mmol), is heated at 130 ° C for 6 hours, getting the target product. The results (table 8) show that such conditions, with or without a catalyst, provide excellent yield and selectivity.

The above experiment is repeated using benzonitrile or acetonitrile (1 ml / mmol) at 110 ° C. Lithium bromide improves the solubility of copper (I) cyanide in an organic solvent, however, excellent results are obtained (table 9) with and without lithium bromide.

Example 7

Large-scale production of 4-cyano-3-nitrobenzotrifluoride from a mixture of 4-bromo-3-nitrobenzotrifluoride and 4-chloro-3-nitrobenzotrifluoride using copper cyanide (I) (method (e)):

A mixture of 4-bromo-3-nitrobenzotrifluoride (0.2 equivalent, 1.7 mol containing 12% 4-chloro-3-nitrobenzotrifluoride) and copper (I) cyanide (1 equivalent) is heated to 130 ° C, and then 4 hours at 130 ° C., the remaining 4-bromo-3-nitrobenzotrifluoride (0.8 equivalents) was added. After heating for another 2 hours at 130 ° C., the cooled mixture was extracted (toluene), washed (aqueous sodium bromide and then sodium bisulfite) and evaporated to give the desired product. The conversion and yield of the target product (calculated on the content of 4-bromo-3-nitrobenzotrifluoride) is 100%. 4-chloro-3-nitrobenzotrifluoride remains unchanged.

Example 8

Preparation of 4-cyano-3-nitrobenzotrifluoride from 4-bromo-3-nitrobenzotrifluoride using alkali metal cyanide and a catalytic amount of copper cyanide (I) in the presence of an interphase catalyst (method (f)):

A mixture of 4-bromo-3-nitrobenzotrifluoride (1 equivalent), potassium cyanide (0.9 equivalent), copper (I) cyanide (0.1 equivalent) and interfacial catalyst (tetraethylammonium bromide or tetrabutylammonium) is heated with benzonitrile, acetonitrile, n -butanol or dimethyl sulfoxide at 110 ° C for 6 hours. The results (table 10) show that excellent selectivity can be obtained by using benzonitrile, acetonitrile or n-butanol at a concentration of 0.2 ml / mmol or 0.4 ml / mmol. If, in addition to acetonitrile (0.4 ml / mmol), a small amount of water (6 μl / mmol), the yield of the target product increases to 44%, while the selectivity remains at a high level.

Example 9

Preparation of 4-cyano-3-nitrobenzotrifluoride from 4-bromo-3-nitrobenzotrifluoride using alkali metal cyanide and a catalytic amount of copper cyanide (I) in the presence of lithium bromide as an interphase catalyst (method (f)):

A mixture of 4-bromo-3-nitrobenzotrifluoride (1 equivalent, 0.02 mol), potassium cyanide (1.2 equivalent, 0.024 mol), copper (I) cyanide (0.1 equivalent, 0.002 mol) and lithium bromide (0, 25 equivalents, 0.005 mol) are heated in 6 ml of acetonitrile at 110 ° C for 18 hours, after which the starting 4-bromo-3-nitrobenzotrifluoride is used up. The cooled mixture was extracted (methyl tert-butyl ether), washed (water), dried (magnesium sulfate) and evaporated to give the desired product.

The conversion is 99%, and the product yield is 89.7% with a purity of 93.8%.

Example 10

Obtaining 4-bromo-3-nitrobenzotrifluoride from 4-chloro-3-nitrobenzotrifluoride using various sources of bromide (method (g)):

A mixture of 4-chloro-3-nitrobenzotrifluoride (1 equivalent) and a bromide source (copper bromide (I), copper bromide (II), lithium or magnesium bromide) (1 equivalent) or a mixture of copper (I) bromide (1 equivalent) and bromide lithium (1 equivalent) is heated for 6 hours at 160 ° C with benzonitrile, diglyme (diethylene glycol dimethyl ether), acetic acid or N-methylpyrrolidone (1 ml / mmol) to obtain the desired product. Table 11 shows that good selectivity can be obtained under various conditions and that a mixture of copper bromide and lithium bromide provides particularly good results. For comparison, in the absence of solvent, poor results were obtained.

.

.

Example 11

Obtaining 4-bromo-3-nitrobenzotrifluoride from 4-chloro-3-nitrobenzotrifluoride using a mixture of copper bromide and lithium bromide (method (g)):

The procedure described in Example 10 above is repeated using a mixture of copper bromide (I) (1 equivalent) and lithium bromide (1 equivalent) with various concentrations of benzonitrile (0.02, 0.04, 0.1, 0.5, 1 or 2 ml / mmol). Table 12 shows that good selectivity is obtained using all of the above conditions, but when benzonitrile is present in an amount of 0.04 ml / mmol, the yield and selectivity are especially high.

The above reaction is repeated, but diglyme (diethylene glycol dimethyl ether) having various concentrations (0.01, 0.02, 0.04, 0.08, 0.1, 0.5, 1 or 2 ml / mmol) is used instead of benzonitrile . Table 13 shows that the optimal conversion, yield and selectivity provides a concentration of 0.02-0.04 ml / mmol.

The above reaction is repeated, but acetic acid, acetonitrile or tetrahydrofuran in various concentrations (0.02, 0.04, 0.1 and 1 ml / mmol) are used instead of benzonitrile. Table 14 shows the results, from which it follows that the optimal concentration depends on the solvent and that the best results are obtained at high concentrations.

Example 12

Obtaining 4-bromo-3-nitrobenzotrifluoride from 4-chloro-3-nitrobenzotrifluoride using various ratios of a mixture of copper bromide (I) and lithium bromide (method (g)):

A mixture of 4-chloro-3-nitrobenzotrifluoride (1 equivalent), copper bromide (I) (1 equivalent) and lithium bromide (2 equivalents) in benzonitrile (4 equivalents) was heated at 180 ° C. for 5 hours. The cooled mixture was extracted with toluene, washed with an aqueous solution of sodium bromide and a solution of sodium bisulfite, and then evaporated to obtain the desired product. The conversion (calculated as 4-chloro-3-nitrobenzotrifluoride) is 84%, the yield is 78%, and the selectivity is 93%.

The above reaction is repeated using copper bromide (I) (0.1 equivalents) and lithium bromide (2 equivalents), with a conversion of 83% and a selectivity of 90%.

Claims (19)

1. The method of obtaining the compounds of formula (I)

where R ¹ means C _1-4 halogenoalkyl; R ² means hydrogen or C _1-4 alkoxy, comprising the interaction of the corresponding orthonitrohalogenbenzene of the formula (II)

where R ¹ and R ² have the above meanings; X represents a fluorine or bromine atom, (a) with an alkali metal cyanide in an anhydrous solvent, optionally in the presence of a catalyst, in the case where X is a Fluorine atom; or (b) with an alkali metal cyanide in the presence of a catalytic amount of copper (I) cyanide and an interfacial catalyst in the case where X is a bromine atom. 2. The method according to claim 1 (a), in which the catalyst is selected from ammonium salts and guanidinium. 3. The method according to claim 1 (a) or 2, in which the alkali metal cyanide is sodium cyanide. 4. The method according to claims 1 (a), 2 or 3, in which 1-2 molar equivalents of cyanide are used. 5. The method according to claim 1 (a) or any one of claims 2 to 4, wherein the solvent is benzonitrile, acetonitrile, tetrahydrofuran or N, N-dimethylformamide. 6. The method according to claim 1 (a) or any one of claims 2-5, wherein the solvent contains less than 1 vol.% Water. 7. The method according to claim 1 (b), in which 0.05-0.2 molar equivalents of copper cyanide (I) are used. 8. The method according to claim 1 (b) or 7, in which potassium cyanide is used. 9. The method according to claims 1 (b), 7 or 8, in which apply 0.5-2 molar equivalents of alkali metal cyanide. 10. The method according to claims 1 (b), 7, 8 or 9, in which the interfacial catalyst is selected from alkali metal or alkaline earth metal bromide, tetraalkylammonium and trialkylbenzylammonium bromides, phosphonium and guanidinium salts, as well as crown ethers. 11. The method according to claim 1 (b) or any one of claims 7 to 10, in which the interfacial catalyst is lithium bromide. 12. The method according to claim 1 (b) or any one of claims 7-11, wherein the concentration of the compound of formula (II) used in the reaction solvent is 0.1 to 2 ml / mmol. 13. The method of obtaining the compounds of formula (I)

where R ¹ means C _1-4 halogenoalkyl; R ² means hydrogen or C _1-4 alkoxy, comprising the interaction of the corresponding ortho-nitrohalogenbenzene formula (II)

where R ¹ and R ² have the above meanings; X represents a bromine atom, with copper cyanide (I) optionally in the presence of a catalyst selected from alkali metal or alkaline earth metal bromide. 14. The method according to item 13, in which the catalyst is lithium bromide. 15. The method according to item 13 or 14, in which apply 0.5-2 molar equivalents of copper cyanide (I). 16. The method according to claims 13, 14 or 15, wherein the amount of catalyst is 0.05-2 molar equivalents. 17. The method according to any one of claims 13-16, wherein the concentration of the compound of formula (II) used in the reaction solvent is 0.1 to 2 ml / mmol. 18. The method according to any one of the preceding paragraphs, in which R ¹ means trifluoromethyl, and R ² is hydrogen or methoxy. 19. The method of claim 18, wherein R ¹ is trifluoromethyl and R ² is hydrogen.