WO1995034548A2

WO1995034548A2 - Process for preparing benzothiophene derivatives

Info

Publication number: WO1995034548A2
Application number: PCT/EP1995/002136
Authority: WO
Inventors: Hermann Uhr
Original assignee: Bayer Aktiengesellschaft
Priority date: 1994-06-16
Filing date: 1995-06-06
Publication date: 1995-12-21
Also published as: DE4420922A1; AU2737395A; WO1995034548A3

Abstract

Benzothiophene-2-carboxylic acid esters and amides having the formula (I), in which R?1, R2, R3, R4 and R5¿ have the meanings given in the description, are produced by a new process in which 3-amino-benzothiophene-2-carboxylic acid esters or amides having the formula (II), in which R?1, R2, R3, R4 and R5¿ have the meanings given in the description are first reacted with diazotising reagents then with substances capable of substituting hydrogen for a diazonium group.

Description

Process for the preparation of benzothiophene derivatives

The application relates to a new process for the preparation of benzothiophene-2-carboxylic acid esters and amides.

Processes are already known for producing benzothiophene-2-carboxylic acid esters and amides. However, the processes described hitherto have the disadvantage that they either start from expensive or poorly accessible starting materials, are multi-stage or require reaction conditions which are difficult to implement technically.

It is described, for example, that methyl benzothiophene-2-carboxylate can be prepared by reacting o-nitrobenzaldehyde and methyl mercaptoacetate in the presence of a base. (see also J.R Beck, J. Org. Chem. 37; 3224 (1972)).

o-Nitrobenzaldehyde is a relatively expensive educt, which is only accessible through complex syntheses, and the space-time yields are extremely unfavorable.

The conversion of o-bromobenzaldehyde with mercaptoacetic acid esters in liquid ammonia and in the presence of large amounts of base gives ethyl benzothiophene-2-carboxylate (see also R. Bengelmaus, Tetrahedron 39, 4153 (1993).

In addition to the poorly available o-bromobenzaldehyde and the immense base excess, reactions in liquid ammonia are technically difficult to achieve.

Starting from o-mercaptobenzoic acid, ethyl benzothiophene-2-carboxylate is obtained in a multistage synthesis (see also C.N. Hsiac, Synth. Comm. 20, 1687 (1990).

BrCH ₂ C0 ₂ Et

By forming the Li salt of fluorobenzene, moving with dimethylformamide and reacting the resulting o-fluorobenzaldehyde with methyl mercaptoacetate in the presence of base, methyl benzothiophene-2-carboxylate is obtained (see also EP 0 568 289). Lithium alkyls require very low temperatures during implementation and, because of their flammability, require expensive safety technology.

It has now been found that benzothiophene-2-carboxylic acid esters and amides of the general formula I

in which

R '

R ^{1 represents} -OR ^ö or N ,.

R ^c

where R ⁶ , R ⁷ and R ⁸ independently of one another represent hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl or aralkyl,

and R ² , R ³ , R ⁴ and R ⁵ each independently represent hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, dialkylamino, nitro or cyano,

obtained by 3-amino-benzothiophene-2-carboxylic acid esters or amides of the formula

in which

R, R, R, R and R have the meaning given above, first reacted with diazotization reagents and then reacted with substances which are suitable for exchanging a diazonium group for hydrogen.

The compounds of formula (I) thus obtained can then, optionally without intermediate isolation, i.e. in the form of a one-pot reaction to the known sulfones of the formula (Ia)

be oxidized.

It can be described as extremely surprising that benzothiophene-2-carboxylic acid esters and amides can be prepared in a smooth reaction by the process according to the invention, since it was not previously known from the prior art that benzothiophene derivatives which have an amino group in the thiophene part included, can be implemented by diazotization.

The method according to the invention is characterized by a number of advantages. The required starting substances and also the reaction components are thus accessible in a simple manner and also in large quantities. In addition, the implementation of the implementation and the isolation of the desired substances pose no problems. In addition, the process according to the invention enables the production of benzothiophene-2-carboxylic acid esters and amides in high yield and good purity.

Formula (II) provides a general definition of the 3-amino-benzothiophene-2-carboxylic acid esters and amides required as starting materials when carrying out the process according to the invention.

R preferably represents -OR or _

R R ⁶ , R ⁷ and R ⁸ independently of one another preferably represent hydrogen, straight-chain or branched alkyl having 1 to 18 carbon atoms, straight-chain or branched alkenyl having 2 to 18 carbon atoms or straight-chain or branched alkynyl having 2 to 18 carbon atoms, which may be one to is substituted several times the same or different by halogen, alkoxy having 1 to 6 carbon atoms, haloalkoxy having 1 to 6 carbon atoms and 1 to 9 identical or different halogen atoms, alkylthio having 1 to 6 carbon atoms, haloalkylthio having 1 to 6 carbon atoms and 1 to 9 identical or different halogen atoms, acyl with 1 to 6 carbon atoms, acyloxy with 1 to 6 carbon atoms, (alkoxy) carbonyl with 1 to 6 carbon atoms in the alkoxy part, amino, which is optionally substituted identically or differently by alkyl or aryl, optionally substituted phenoxy or pyridyloxy, nitro or cyano, further for Cyc loalkyl, consisting of 1 to 4 ring systems, with 3 to 18

Carbon atoms which are optionally substituted one or more times, identically or differently, by halogen, alkyl having 1 to 4 carbon atoms, haloalkyl having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, alkoxy having 1 to 4 carbon atoms, haloalkoxy having 1 to 4 coblene atoms and 1 to

5 identical or different halogen atoms, alkylthio with 1 to 4 carbon atoms, haloalkylthio with 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, nitro or cyano, furthermore for aryl, which is optionally substituted one to five times by halogen, alkyl with 1 to 10 carbon atoms, haloalkyl with 1 to 8 carbon atoms and 1 to 8 identical or different halogen atoms, alkoxy with 1 to 10 carbon atoms, haloalkoxy with 1 to 8 carbon atoms and 1 to 8 identical or different halogen atoms, alkylthio with 1 to 10 carbon atoms , Haloalkylthio with 1 to 10 carbon atoms, haloalkylthio with 1 to 8

Carbon atoms and 1 to 8 identical or different halogen atoms, amino, monoalkylamino with straight-chain or branched alkyl radicals with 1 to 6 carbon atoms, dialkylamino with identical or different, straight-chain or branched alkyl radicals with 1 to 6 carbon atoms each, cycloalkyl with 1 to 6 carbon atoms, methyl lendioxy, di-fluoromethylene-dioxy, chlorofluoromethylene-dioxy, dichloromethylene-dioxy, nitro or cyano, further for aralkyl, where the alkyl radical is straight or branched and consists of 1 to 8 carbon atoms and aryl is preferably phenyl, which may be one to four times, identical or different is substituted by halogen, alkyl having 1 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, alkoxy having 1 to 6 carbon atoms, haloalkoxy having 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, alkylthio with 1 to 6 carbon atoms, haloalkylthio with 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, amino, monoalkylamino with straight-chain and branched alkyl radicals with 1 to 6 carbon atoms, dialkylarnino with identical or different, straight-chain or branched alkyl radicals with 1 to 6 each Carbon atoms, cycloalkyl with 1 to 6 carbon atoms,

Methyl endioxy, Difiuormethylenendioxy, Chlorfluormethylenendioxy, Dichlormethylenendioxy, Nitro or Cyano.

R ² , R ³ , R ⁴ and R ⁵ each independently of one another preferably represent hydrogen, halogen, alkyl having 1 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms,

Alkoxy with 1 to 6 carbon atoms, haloalkoxy with 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, alkylthio with 1 to 6 carbon atoms, haloalkylthio with 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, Dialkylamino with the same or different, straight-chain or branched alkyl radicals each having 1 to 6 carbon atoms, nitro or cyano.

R ¹ particularly preferably represents -OR ⁶ or

R ⁶ , R ⁷ and R ⁸ independently of one another are particularly preferably

Hydrogen, straight-chain or branched alkyl having 1 to 14 carbon atoms, straight-chain or branched alkenyl having 2 to 14 Carbon atoms or straight-chain or branched alkynyl having 2 to 14 carbon atoms, which is optionally substituted one to four times in the same or different way by fluorine, chlorine, alkoxy having 1 to 5 carbon atoms, haloalkoxy having 1 to 5 carbon atoms and 1 to 5 fluorine and / or Chlorine atoms, alkylthio with 1 to 5 carbon atoms,

Haloalkylthio with 1 to 5 carbon atoms and 1 to 5 fluorine and / or chlorine atoms, acyl with 1 to 5 carbon atoms, acyloxy with 1 to 5 carbon atoms, in the alkoxy part, alkoxy carbonyl with 1 to 5 carbon atoms, amino, which may be substituted identically or differently is by alkyl with 1 to 4 carbon atoms and / or phenyl,

Phenoxy, pyridyloxy, nitro or cyano, furthermore for cycloalkyl, consisting of 1 to 3 ring systems, with 3 to 14 carbon atoms, which is optionally substituted one to four times by fluorine / chlorine, alkyl having 1 to 4 carbon atoms, Alkoxy with 1 to 4 carbon atoms, alkylthio with 1 to 4

Carbon atoms, nitro or cyano, further for aryl, which is optionally mono- to tetrasubstituted by fluorine, chlorine, alkyl having 1 to 8 carbon atoms, haloalkyl having 1 to 6 carbon atoms and 1 to 6 fluorine and / or chlorine atoms, alkoxy with 1 up to 8 carbon atoms, haloalkoxy with 1 to 6 carbon atoms and 1 to 6 fluorine and / or chlorine atoms, alkylthio with 1 to 8 carbon atoms, haloalkylthio with 1 to 6 carbon atoms and 1 to 6 fluorine and / or chlorine atoms, amino, monoalkylamino with alkyl radicals of 1 to 4 carbon atoms, dialkylamino with the same or different alkyl radicals each with 1 to 4 carbon atoms, cycloalkyl with

1 to 6 carbon atoms, methylenedioxy, difluoromethylenedioxy, chlorofluoromethylenedioxy, dichloromethylenedioxy, nitro or cyano, furthermore for aralkyl, the alkyl radical being straight or branched and consisting of 1 to 8 carbon atoms and aryl for phenyl, which is optionally substituted one to four times is with fluorine, chlorine, alkyl

1 to 4 carbon atoms, haloalkyl with 1 to 4 carbon atoms and 1 to 4 fluorine and / or chlorine atoms, alkoxy with 1 to 4 carbon atoms, haloalkoxy with 1 to 4 carbon atoms and 1 to 4 fluorine and / or chlorine atoms, alkylthio with 1 to 4 carbon atoms, haloalkylthio with 1 to 4 carbon atoms and 1 to 4 fluorine and / or chlorine atoms, amino, Monoalkylamino with alkyl radicals of 1 to 4 carbon atoms, dialkylamino with the same or different alkyl radicals each with 1 to 4 carbon atoms, cycloalkyl with 1 to 6 carbon atoms, methylenedioxy, difluoromethylenedioxy, chlorofluoromethylenedioxy, dichloromethylenedioxy, nitro or cyano.

R ² , R ³ , R ⁴ and R ⁵ each independently of one another particularly preferably represent hydrogen, chlorine, fluorine, alkyl having 1 to 4 carbon atoms, haloalkyl having 1 to 4 carbon atoms and 1 to 6 fluorine and / or chlorine atoms, alkoxy 1 to 4 carbon atoms, haloalkoxy with 1 to 4 carbon atoms and 1 to 6 fluorine and / or chlorine atoms, alkylthio with

1 to 4 carbon atoms, haloalkylthio with 1 to 4 carbon atoms and 1 to 6 fluorine and / or chlorine atoms, dialkylamino with the same or different, straight-chain or branched alkyl radicals each with 1 to 6 carbon atoms, nitro or cyano.

If, for example, 3-amino-benzothiophenecarboxylic acid methyl ester is reacted in succession with sodium nitrite and hypophosphorous acid to give methyl benzothiophene carbonate, the reaction can be described by the following formula.

The process according to the invention can be divided into two steps:

1. Diazotization

2. Exchange of the diazonium salt residue for hydrogen.

The diazonium salt is generally not isolated, but is immediately reacted further. However, isolation of the diazonium salt, for example in the case of the diazonium fluoroborates, is also possible.

The diazotization of 3-aminobenzothiophene-carboxylic acid esters and amides of the general formula (II) is generally carried out in acidic, aqueous solution which optionally cosolvents are added, carried out by reaction with sodium nitrite. For this purpose, the sodium nitrite is generally added dropwise as an aqueous solution to an acidic solution, suspension or emulsion of 3-aminobenzothiophene-carboxylic acid esters or amides of the general formula (II). However, the nitrite solution can also be introduced and the solution of the 3-aminobenzothiophene carboxylic acid ester or amide (II) can be added dropwise.

Mineral acids, as well as organic acids, and mixtures of one or more acids can be used to prepare the acidic solutions. Hydrochloric acid, sulfuric acid, phosphoric acid are preferably suitable as mineral acids; formic acid, acetic acid, trifluoroacetic acid are preferably used as organic acids. The concentration of the acids can be varied within a very wide range, in general they are 5 to 95%.

In general, work is carried out in aqueous solutions, but cosolvents can also be added if appropriate. Alcohols such as methanol, ethanol, propanol, isopropanol, butanol, ethylene glycol or polyethylene glycols are preferred here.

The reaction temperature for diazonium salt formation can be varied within a wide range. In general, temperatures between -20 ° C and 50 ° C, preferably at -10 ° C to 25 ° C.

However, it is also possible to prepare the diazonium salt by converting the 3-aminobenzothiophenecarboxylic acid esters and amides (II) with organic nitrites. In general, aliphatic nitrites, preferably nitrites such as methyl nitrite, ethyl nitrite, propyl nitrite, iso-propyl nitrite, butyl nitrite, sec-butyl nitrite, iso-butyl nitrite, tert-butyl nitrite, or benzyl nitrite, or isopentyl nitrite are used.

The process is carried out in aqueous or organic solutions, which may be acidified by adding mineral acids or organic acids. All customary solvents can be used as organic solvents in this process. Hydrocarbons such as benzene, toluene or hexane, halogenated hydrocarbons such as carbon tetrachloride, chloroform, methylene chloride, ethers such as diethyl ether, dipropylene ether, dibutyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, 1,3-dioxlan, glycol dimethyl ether are preferably usable. Alcohols such as methanol, ethanol, propanol, iso-propanol, butanol, tert-butanol, also dimethylformamide, acetonitrile, hexamethylphosphoric acid amide, nitromethane, dimethyl sulfoxide.

The acids that can optionally be added are either mineral acids or organic acids or mixtures of different acids. Hydrochloric acid, sulfuric acid, phosphoric acid, borofluorohydric acid are preferably used as mineral acids; formic acid, acetic acid, trifluoroacetic acid are preferably used as organic acids. The reaction temperatures can be varied within a very wide range and are between -20 ° C and + 100 ° C depending on the solvent.

In the case of the conversion of the 3-aminobenzothiophenecarboxylic acid esters and amides (II) with organic nitrites, the second sub-step (replacement of the diazonium salt residue for hydrogen) can be dispensed with in many cases because the solvents required for this reaction already serve as a hydrogen source.

The solutions as described above or the isolated diazonium salt are then reacted with reagents which can exchange the diazonium salt group for hydrogen. For this purpose, preference is given to using H ₃ PO ₂ solutions, metals, triethylsilane or metal salts, preferably iron, zinc, tin, copper, Cu (I) salts such as Cu ₂ O, CuCl, Cu ₂ SO ₄ or complex hydrides, preferably Sodium or potassium borohydride, LiAlH ₄ , tributyltin hydride, or reaction is carried out directly with hydrogen gas, if appropriate in the presence of catalysts, preferably Raney nickel, Raney cobalt, palladium or platinum on various supports, such as, for example, carbon, barium sulfate. This can be done under pressure or without pressure. Organic aldehydes in alkaline solution can also serve as reducing agents.

Depending on the solvent and the reducing agent, the reaction temperature for this substep can be varied over a wide range. Generally one works between -20 ° C and 100 ° C, preferably between -10 ° C and 50 ° C.

The solvents used for this step correspond to those used in the preparation of the diazonium salts (if the diazonium salts are not be isolated). If the diazonium salt has been isolated, it is also possible to work in aqueous solution and / or organic solvents which may have been acidified by organic acids or mineral acids. In some cases it is also necessary to work in alkaline solutions.

All customary solvents can be used as organic solvents in this process. Hydrocarbons such as benzene, toluene or hexane, halogenated hydrocarbons such as carbon tetrachloride, chloroform, methylene chloride, ethers such as diethyl ether, dipropylene ether, di-butyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, 1,3-dioxolane, are preferably usable. Glycol dimethyl ether, alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, and also dimethylformamide, acetonitrile, hexamethylphosphoric acid amide, nitromethane, dimethyl sulfoxide.

The reaction products are isolated in the usual way, either by filtering off or by extraction with organic solvents. If necessary, they can be purified in the usual way by crystallization, distillation, sublimation or chromatography.

The benzothiophene-2-carboxylic acid esters and amides obtained serve as starting materials in the production of urokinase inhibitors (EP 0 568 289) and fungicides (EP 0 512 349).

If 3-amino-benzothiophene-2-carboxylic acid ester of the general formula II is used in the process according to the invention, where R ^{1 is} -OR ⁶ and R ² , R ³ , R ⁴ and R ⁵ and R ^{6 have} the meaning described above, so can the benzothiophene-2-carboxamides of the general formula (I), wherein R ¹ for

_M stands

and R ² , R ³ , R ⁴ , R ⁵ , R ⁷ and R ^{8 have} the meanings described above alternatively also obtained if one has in this case arisen during the reaction Benzothiopen-2-carboxylic acid esters of the general formula (I), where R ^{1 is} -OR ⁶ and R ² , R ³ , R ⁴ , R ⁵ and R ^{6 have} the meaning described above with amines of the general formula (III)

where R ⁷ and R ^{8 have} the meaning described above,

implements.

The following scheme should serve as an explanation:

This reaction step can be carried out either with or without a solvent. However, it is also possible to first saponify the benzothiophene-2-carboxylic acid esters to give the acid and then react them with the amine (HI) either via the acid chloride stage or directly in the presence of a dehydrating agent.

The 3-amino-benzothiophene-2-carboxylic acid esters or amides of the general formula (II) which can be used as starting materials are known or can be prepared by known processes (see: JR Beck, J. Org. Chem. 37, 3224 (1972 ); Coppola, Gary M .; J. Heterocycl. Chem., 19, 717 (1982); U.S. Patent 3,755,583; DE-OS 2,165,962).

The implementation of the method according to the invention is illustrated by the following examples. Production Example 1

30 ml of 95% H ₂ SO _{4 are} initially introduced and 6.8 g (33 mmol) of 3-amino-benzothiophene-2-carboxylic acid methyl ester are added. The clear, yellow-green solution is cooled to 0 ° C. and 50 ml of water are carefully added. The mixture is cooled to -8 ° C., a solution of 2.3 g of NaNO ₂ in 15 ml of H ₂ O is added dropwise and the mixture is stirred for 30 minutes. 100 ml of H ₂ O and then 120 ml of a 50% H ₃ PO ₂ solution are then added at ~ 0 ° C. The mixture is stirred at room temperature for 6 h, filtered off, washed with water and dried in vacuo.

Yields g (Δ 79% of theory) F _p = 65 ° C

Benzothiophene-2-carboxylic acid methyl ester.

Production Example 2

1.8 g (15 mmol) of isoamyl nitrite are placed in 30 ml of dry dimethylformamide, brought to 65 ° C. and within 10 minutes with a solution of 2.07 g (10 mmol) of 3-amino-benzothiophene-2-carboxylic acid methyl ester in dry Dimethylformamide added. The mixture is stirred for 15 minutes at this temperature, allowed to cool and poured into 100 ml of 20% hydrochloric acid. It is extracted twice with dichloromethane, the combined organic phases are washed with water, dried over magnesium sulfate and evaporated.

Yield: 1.18 g (Δ 61% of theory) F _D = 65 ^c

Claims

1. Process for the preparation of benzothiophene-2-carboxylic acid esters and amides of the formula

in which

R ⁷ R ^{1 stands} for -OR ⁶ or - f ^stands ..

R ⁸

characterized in that 3-amino-benzothiophene-2-carboxylic acid esters or amides of the formula

in which

R ¹ , R ² , R ³ , R ⁴ and R ^{5 have} the meaning given above,

first reacted with diazotization reagents and then reacted with substances that are suitable for exchanging a diazonium group for hydrogen.

2. The method according to claim 1, characterized in that one uses compounds of formula (H) in which

R ⁷ R ¹ preferably represents -OR ⁶ or _M ^/ ,

^" % ⁸

wherein

R ⁶ , R ⁷ and R ⁸ independently of one another preferably represent hydrogen, straight-chain or branched alkyl having 1 to 18 carbon atoms, straight-chain or branched alkenyl having 2 to 18 carbon atoms or straight-chain or branched alkynyl having 2 to 18 carbon atoms, which may be one to is substituted several times the same or different by halogen, alkoxy having 1 to 6 carbon atoms, haloalkoxy having 1 to 6 carbon atoms and 1 to 9 identical or different halogen atoms, alkylthio having 1 to 6 carbon atoms, haloalkylthio having 1 to 6 carbon atoms and 1 to 9 identical or different halogen atoms, acyl with 1 to 6 carbon atoms,

Acyloxy having 1 to 6 carbon atoms, (alkoxy) carbonyl having 1 to 6 carbon atoms in the alkoxy part, amino, which is optionally substituted identically or differently by alkyl or aryl, optionally substituted phenoxy or pyridyloxy, nitro or cyano, furthermore represents cycloalkyl from 1 to 4 ring systems, with 3 to 18 carbon atoms, which may be one or more times, is identical or differently substituted by halogen, alkyl having 1 to 4 carbon atoms, haloalkyl having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, alkoxy having 1 to 4 carbon atoms, haloalkoxy having 1 to 4

5 carbon atoms and 1 to 5 identical or different

Halogen atoms, alkylthio with 1 to 4 carbon atoms, haloalkylthio with 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, nitro or cyano, furthermore for aryl, which may be one to five times

10 is substituted by halogen, alkyl having 1 to 10 carbon atoms,

Haloalkyl with 1 to 8 carbon atoms and 1 to 8 identical or different halogen atoms, alkoxy with 1 to 10 carbon atoms, haloalkoxy with 1 to 8 carbon atoms and 1 to 8 identical or different halogen atoms, alkylthio

15 with 1 to 10 carbon atoms, haloalkylthio with 1 to 10

Carbon atoms, haloalkylthio with 1 to 8 carbon atoms and 1 to 8 identical or different halogen atoms, amino, monoalkylamino with straight-chain or branched alkyl radicals with 1 to 6 carbon atoms, dialkylamino with identical or different

20 different, straight-chain or branched alkyl radicals, each with 1 to

6 carbon atoms, cycloalkyl having 1 to 6 carbon atoms, methylenedioxy, difluoromethylenedioxy, chlorofluoromethylenedioxy, dichloromethylenedioxy, nitro or cyano, furthermore for aralkyl, the alkyl radical being straight or branched

25 and consists of 1 to 8 carbon atoms and aryl preferably for

Phenyl which is optionally mono- to tetrasubstituted, identically or differently, by halogen, alkyl having 1 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, alkoxy having 1 to

30 6 carbon atoms, haloalkoxy with 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, alkylthio with 1 to 6 carbon atoms, haloalkylthio with 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, amino, monoalkylamino with straight-chain and

35 branched alkyl radicals with 1 to 6 carbon atoms, dialkylamino with the same or different, straight-chain or branched alkyl radicals each having 1 to 6 carbon atoms, cycloalkyl having 1 to 6 carbon atoms, methylenedioxy, difluoromethylenedioxy, chlorofluoromethylenedioxy, dichloromethylenedioxy, nitro or cyano, and

R ² , R ³ , R ⁴ and R ⁵ each independently represent preferably

Hydrogen, halogen, alkyl with 1 to 6 carbon atoms, haloalkyl with 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, alkoxy with 1 to 6 carbon atoms, haloalkoxy with 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, alkylthio with 1 to 6 carbon atoms, haloalkylthio having 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, dialkylamino having the same or different, straight-chain or branched alkyl radicals each having 1 to 6 carbon atoms, nitro or cyano.

3. The method according to claim 1, characterized in that one uses compounds of formula (II) in which

R ¹ preferably represents -OR ⁶ or represents.

woπn

R ⁶ , R ⁷ and R ⁸ independently of one another preferably represent hydrogen, straight-chain or branched alkyl having 1 to 18 carbon atoms, straight-chain or branched alkenyl having 2 to 1 8 carbon atoms or straight-chain or branched alkynyl having 2 to 18 carbon atoms, which may be a is substituted several times, identically or differently, by halogen, alkoxy having 1 to 6 carbon atoms, haloalkoxy having 1 to 6 carbon atoms and 1 to 9 identical or different halogen atoms, alkylthio having 1 to 6 carbon atoms, haloalkylthio with 1 to 6 carbon atoms and 1 to 9 identical or different halogen atoms, acyl with 1 to 6 carbon atoms, acyloxy with 1 to 6 carbon atoms, (alkoxy) carbonyl with 1 to 6 carbon atoms in the alkoxy part, amino, which may optionally substitute 5 identical or different is alkyl or aryl, optionally substituted phenoxy or pyridyloxy, nitro or cyano, furthermore cycloalkyl, consisting of 1 to 4 ring systems with 3 to 18 carbon atoms, which may be one or more times,

10 is identical or differently substituted by halogen, alkyl with 1 to

4 carbon atoms, haloalkyl with 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, alkoxy with 1 to 4 carbon atoms, haloalkoxy with 1 to 4 carbon atoms and 1 to 5 identical or different

15 halogen atoms, alkylthio with 1 to 4 carbon atoms,

Haloalkylthio with 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, nitro or cyano, furthermore represent aryl, which is optionally mono- to pentasubstituted by halogen, alkyl having 1 to 10 carbon atoms,

20 haloalkyl with 1 to 8 carbon atoms and 1 to 8 identical or different halogen atoms, alkoxy with 1 to 10 carbon atoms, haloalkoxy with 1 to 8 carbon atoms and 1 to 8 identical or different halogen atoms, alkylthio with 1 to 10 carbon atoms, haloalkylthio with 1 to 10th

25 carbon atoms, haloalkylthio with 1 to 8 carbon atoms and 1 to 8 identical or different halogen atoms, amino, monoalkylamino with straight-chain or branched alkyl radicals with 1 to 6 carbon atoms, dialkylamino with the same or different, straight-chain or branched alkyl radicals each with 1 to

30 6 carbon atoms, cycloalkyl with 1 to 6 carbon atoms,

Methylenedioxy, difluoromethylenedioxy, chlorofluoromethylenedioxy, dichloromethylenedioxy, nitro or cyano also stand for aralkyl, the alkyl radical being straight or branched and consisting of 1 to 8 carbon atoms and preferably aryl for

35 is phenyl, which may be one to four times the same or is differently substituted by halogen, alkyl having 1 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, alkoxy having 1 to 6 carbon atoms, haloalkoxy having 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms , Alkylthio with 1 to 6 carbon atoms, haloalkylthio with 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, amino, monoalkylamino with straight-chain and branched alkyl radicals with 1 to 6 carbon atoms, dialkylamino with identical or different, straight-chain or branched

Alkyl radicals each having 1 to 6 carbon atoms, cycloalkyl having 1 to 6 carbon atoms, methylenedioxy, difluoromethylenedioxy, chlorofluoromethylenedioxy, dichloromethylenedioxy, nitro or cyano, and

R ² , R ³ , R ⁴ and R ⁵ each independently of one another preferably represent hydrogen, halogen, alkyl having 1 to 6 carbon atoms,

Haloalkyl with 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, alkoxy with 1 to 6 carbon atoms, haloalkoxy with 1 to 6 carbon atoms and 1 to 6 identical or different halogen atoms, alkylthio with 1 to 6 carbon atoms, haloalkylthio with 1 to 6 carbons ¬ atoms and 1 to 6 identical or different halogen atoms, dialkylamino with the same or different, straight-chain or branched alkyl radicals each having 1 to 6 carbon atoms, nitro or cyano.

4. The method according to claim 1, characterized in that sodium nitrite, methyl nitrite, ethyl nitrite, propyl nitrite, isopropyl nitrite, butyl nitrite, sec-butyl nitrite, iso-butyl nitrite, tert. -Butyl nitrite, isopentyl nitrite or benzyl nitrite are used as diazotization reagents.

5. The method according to claim 1, characterized in that solutions of hypophosphorous acid, metals, metal salts, triethylsilane, complex

Hydrides, hydrogen in the presence of a catalyst or organic Aldeyhde used in alkaline solution as substances for the exchange of the diazonium group for hydrogen.

6. The method according to claim 1, characterized in that one works in the implementation of the diazotization at temperatures between -20 ° C and + 50 ° C.

7. The method according to claim 1, characterized in that one works when replacing the diazonium group for hydrogen at temperatures between -20 ° C and + 100 ° C.