Organic compounds -- part of the class 532-570 series – Organic compounds – Nitriles
Reexamination Certificate
2000-01-24
2002-10-08
Killos, Paul J. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitriles
C558S406000
Reexamination Certificate
active
06462218
ABSTRACT:
The present invention relates to a process for preparing 3-cyano-2,4-dihalogeno-5-fluoro-benzoic acids, to intermediates for carrying out the process and to processes for preparing these intermediates.
3-Cyano-2,4-dichloro-5-fluoro-benzoic acid is known from DE-A-3 702 393. It is prepared from 3-amino-2,4-dichloro-5-fluoro-benzoic acid by diazotization and reaction of the diazonium salt with cyanide salts. This process is unfavourable, in particular when it is carried out on a relatively large scale.
The present invention provides
1. Process for preparing 3-cyano-2,4-dihalogeno-5-fluorobenzoic acids of the formula (I)
in which
X and Y independently of one another each represent halogen by hydrolytic cleavage of
a) 3-cyano-2,4-dihalogeno-5-fluorobenzamides of the formula (II)
in which
X and Y independently of one another each represent halogen, or
b) 1,3-dicyano-2,4-dihalogeno-5-fluorobenzenes of the formula (III)
in which
X and Y independently of one another each represent halogen, or
c) 3-cyano-2,4-dihalogeno-5-fluorobenzoic esters of the formula (IV)
in which
X and Y independently of one another each represent halogen and
R represents C
1-4
-alkyl which may optionally be substituted.
2. The novel compounds of the formulae (II)
and (IV)
in which
X and Y independently of one another each represent halogen and
R represents C
1-4
-alkyl which may optionally be substituted,
except for methyl3-cyano-2,4,5-trifluorobenzoate.
3. Process for preparing 3-cyano-2,4-dihalogeno-5-fluoro-benzamides of the formula (II)
or esters of the formula (IV)
characterized in that 1,3-dicyano-2,4-dihalogeno-5-fluorobenzenes of the formula (III)
in which
X and Y are each as defined above,
are hydrolyzed in the presence of water or in the presence of alcohols.
4. The novel compounds of the formula (III)
in which
X and Y represent different radicals from the group consisting of fluorine and chlorine, or both radicals represent chlorine.
5. Process for preparing the compounds of the formula (III)
in which
X and Y represent different radicals from the group consisting of fluorine and chlorine,
characterized in that 1,2,4-trifluoro-3,5-dicyanobenzene(2,4,5-trifluoro-isophthalonitrile) is reacted with a metal halide.
1,2,4-Trifluoro-3,5-dicyanobenzene and its preparation are known from EP-A-307 897.
In the above formulae, X and Y each preferably represent fluorine or chlorine. In the compounds of the formulae (II) and (IV), they particularly preferably represent identical radicals fluorine or chlorine.
Among the compounds of the formula (III), particular preference is given to 2,4-dichloro-5-fluoroisophthalonitrile.
R preferably represents methyl, ethyl, propyl or benzyl.
If 3-cyano-2,4,5-trifluorobenzamide is used as starting material in the process a) for preparing 3-cyano-2,4,5-trifluorobenzoic acid, the reaction can be illustrated by the following formula scheme:
The amides of the formula (II) used as starting materials are novel. Their preparation is described further below.
The hydrolysis is carried out in the presence of acids and water. Suitable for use as acids are organic and inorganic strong acids. Examples which may be mentioned are HCl, HBr, sulphuric acid, methanesulphonic acid, trifluoromethanesulphonic acid, benzenesulphonic acid, toluenesulphonic acid and strongly acidic ion exchangers in the presence of water.
The solvent used can be an excess of the acid used as reagent, or an organic solvent. Suitable organic solvents are acids, such as formic acid, acetic acid, propionic acid, ethers, such as dimethoxyethane, dioxane, ketones, such as acetone, butanone.
The reaction components may be added in any order. The mixture is subsequently heated to the required temperature.
The reaction temperature is in the range from 0 to 200° C., preferably from 20 to 150° C.
The reaction can be carried out under atmospheric pressure or under a pressure of from 0 to 50 bar, preferably from 0 to 6 bar.
The products are filtered off from the reaction mixture, if appropriate after dilution with water. If a large excess of acid or a solvent is used, it may be advantageous to carry out a distillation and to isolate the product by extraction.
If 4-chloro-2,5-difluoro-isophthalonitrile is used as starting material for preparing 4-chloro-2,5-difluoro-3-cyanobenzoic acid according to process 1b), the reaction can be illustrated by the reaction scheme below:
2,4,5-Trifluoro-isophthalonitrile is known from the literature (EP-A-307 897). 2,4-Dichloro-5-fluoro-isophthalonitrile is novel. Its preparation is described further below.
The hydrolysis with acids is carried out in the presence of water. Suitable for use as acids are organic and inorganic strong acids. Examples which may be mentioned are HCl, HBr, sulphuric acid, methanesulphonic acid, trifluoromethanesulphonic acid, benzenesulphonic acid, toluenesulphonic acid and strongly acidic ion exchangers in the presence of water.
The solvent used can be an excess of the acid used as reagent, or an organic solvent. Suitable organic solvents are acids, such as formic acid, acetic acid, propionic acid, ethers, such as dimethoxyethane, dioxane, ketones, such as acetone, butanone.
The reaction components may be added in any order. The mixture is subsequently heated to the required temperature.
The reaction temperature is in the range from 0 to 200° C., preferably from 20 to 150° C.
The reaction can be carried out under atmospheric pressure or under a pressure of from 0 to 50 bar, preferably from 0 to 6 bar.
The products are filtered off from the reaction mixture, if appropriate after dilution with water. If a large excess of acid or a solvent is used, it may be advantageous to carry out a distillation and to isolate the product by extraction.
If methyl 3-cyano-2,4,5-trifluoro-benzoate is used as starting material in the process 1c) for preparing 3-cyano-2,4,5-trifluorobenzoic acid, the reaction can be illustrated by the formula scheme below:
The esters of the formula (IV) used as starting materials are novel. Their preparation is described further below.
The hydrolysis is carried out in the presence of acids and water. Suitable for use as acids are organic and inorganic strong acids. Examples which may be mentioned are HCl, HBr, sulphuric acid, methanesulphonic acid, trifluoromethanesulphonic acid, benzenesulphonic acid, toluenesulphonic acid and strongly acidic ion exchangers in the presence of water.
The solvent used can be an excess of the acid used as reagent, or an organic solvent. Suitable organic solvents are acids, such as formic acid, acetic acid, propionic acid, ethers, such as dimethoxyethane, dioxane, ketones, such as acetone, butanone.
The reaction components may be added in any order. The mixture is subsequently heated to the required temperature.
The reaction temperature is in the range from 0 to 200° C., preferably from 20 to 150° C.
The reaction can be carried out under atmospheric pressure or under a pressure of from 0 to 50 bar, preferably from 0 to 6 bar.
The products are extracted from the reaction mixture, if appropriate after dilution with water. If a large excess of acid or a solvent is used, it may be advantageous to carry out a distillation.
As already mentioned, the compounds of the formula (IV) are novel.
If 2,4-dichloro-5-fluoro-isophthalonitrile is used as starting material for their preparation according to process 3), the reaction can be represented by the formula scheme below:
The reaction proceeds via the iminoester intermediate and its hydrolysis with water. The formation of the corresponding amide is observed as a side reaction. If no water is added, the amide formation becomes the predominant reaction (see below).
2,4,5-Trifluoro-isophthalonitrile is known from the literature (EP-A-307 897). 2,4-Dichloro-5-fluoro-isophthalonitrile is novel, its preparation is described further below.
The compound of the formula (II) is prepared by hydrolysis of the corresponding dinitriles with acids in the presence of water and alcohols.
The reaction is carried out in the presence of from 1 to 10 equivalents of wate
Hallenbach Werner
Marhold Albrecht
Bayer Aktiengesellschaft
Killos Paul J.
LandOfFree
Method for preparing 3-cyano-2,4-dihalogeno-5-fluoro-Benzoic... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for preparing 3-cyano-2,4-dihalogeno-5-fluoro-Benzoic..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for preparing 3-cyano-2,4-dihalogeno-5-fluoro-Benzoic... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2997092