|Title of Invention||
"PROCESS FOR THE PREPARATION OF PRODUCTS OF FORMULA 1 ( POLYHALOGENATED PARATRIFLUOROMETHYLANILINES)"
|Abstract||Process for the preparation of products of formula (I): from reactants of formula (II): in the presence of ammonia and at a temperature of between 180 and 270°C.|
|Full Text||The subject-matter of the present invention
is a novel process for the preparation of polyhalogenated para-trifluoromethylanilines, more particularly of dihalo-para-trifluoromethylanilines.
Processes making possible the preparation of anilines substituted by a halogen atom have formed the subject of many studies and of numerous patents or publications.
Thus, the subject-matter of United States Patent 4,096,185 is a process for the amination of halogenated aromatic compounds, such as para-trif luoromethylaniline, from para-chloro-trifluoromethylbenzene and with the use of a specific catalytic combination targeted at improving the yield of the reaction.
The process of United States Patent 4,197,259 discloses the preparation of monohalogenated anilines by the use of difficult reaction conditions related to the use of an alkali metal amide as aminating agent; this is because, as the use of such an alkali metal amide requires the reaction to be carried out in the absence of any trace of water in the reaction mixture, these reaction conditions render fairly problematic the
implementation of such a process on an industrial scale; in addition, such reaction conditions involve significant difficulties related to the dissipation of the heat of reaction.
East German Patent 292,238 relates to the preparation of nitrated and monohalogenated anilines.
European Patent Application 173,202 discloses the preparation of 5-chloro-2-nitroanilines.
Japanese Patent 5 255,206 and European Patent Application 543,633 have, as subject-matter, the preparation of monofluoroanilines and of monofluorinated trifluoromethylanilines respectively.
Thus, despite the large number of studies carried out to develop novel synthetic routes, in particular for the purpose of improving the known processes for the preparation of halogenated anilines, virtually all the methods known to date only relate to monohalogenated anilines alone.
In addition, and although Japanese Patent 7 025,834 has disclosed a process for the preparation of polyhalogenated nitroanilines, it is often impossible to apply these reactions to compounds substituted by a trifluoromethyl group due, inter alia, to the low reactivity conferred on the reactants by this trifluoromethyl group.
One of the aims of the present invention is to provide a method for the preparation of polyhalogenated para-trifluoromethylanilines.
Another aim of the invention is to solve the problems related to the preparation of 2,6-dihalogenated and 4-trifluoromethylated anilines while avoiding the formation of polyamination products and products from the hydrogenation of the aromatic residue.
An additional aim of the process of the invention is to promote the formation of polyhalogenated para-trifluoromethylanilines instead of meta-trifluoromethylated isomers.
It has now been found that these objectives can be achieved in all or part by virtue of the process according to the invention.
It is a process for the preparation of polyhalogenated derivatives of trifluoromethylaniline by reaction [lacuna] polyhalogenated
trifluoromethylbenzenes, particularly of 3,4,5-trihalo-trifluoromethylbenzenes, for example of 4-bromo-3,5-dichloro-trifluoromethylbenzene or of 3,4,5-trichloro-trifluoromethylbenzene, with ammonia.
The reaction of the process according to the invention is carried out at a temperature of between 150 and 350°C, more particularly between 180 and 270°C, and advantageously in a polar organic solvent.
The reaction of the invention can, in
addition to ammonia, be carried out in the presence of an alkali metal halide.
Thus, the process according to the invention makes possible the preparation of the products of formula (I):
from reactants of formula (II):
When it is present, the alkali metal halide is present in a catalytic amount, particularly in an amount of between 1 and 50% of the amount of reactant of formula (II) used, more particularly in an amount of between 5 and 20%. The alkali metal halide is advantageously an alkali metal fluoride or bromide, preferably a lithium halide.
The process according to the invention is advantageously carried out with a content of water in the reaction mixture such that the H20/NH3 ratio is less than 80/100, preferably less than 20/100, more preferably less than 2 /1OO.
The organic solvent optionally employed in the invention is preferably a polar organic solvent, more preferably a nonionic polar organic solvent, for example an N-alkylpyrrolidone, the alkyl radical of which preferably has from 1 to 12 carbon atoms. The use of N-methylpyrrolidone is preferred.
The pressure which prevails in the mixture during the reaction according to the invention is an autogenous pressure resulting from the use of a closed system, for example an autoclave, in order to exert the best control over the amount of ammonia present.
The product resulting from the reaction according to the invention is separated from the reaction mixture by any conventional means, for example by distillation, by extraction or by extraction followed by distillation, or by isolation of salts obtained by the action of hydrochloric acid.
For the purpose of isolating the aniline derivative obtained, the unreacted polyhalogenated para-trifluoromethylbenzene is separated from the reaction mixture. In the case where only a small amount of the benzene derivative used is present, this stage can be omitted.
By carrying out the reaction of the process according to the invention in a reactor equipped with a distillation apparatus, the targeted aniline derivative and the unreacted benzene derivative are directly separated from the reaction mixture by distillation.
In order to isolate the targeted reaction product by extraction, water and an organic solvent of low boiling point, for example ether, dichloromethane or hexane, are added to the reaction mixture. After separation of the aqueous phase, the organic phase is distilled in order to separate the targeted aniline derivative from the unreacted benzene derivative. The benzene derivative, thus separated, is then recycled as reactant for the process of the invention.
Another method of separation of the reaction
product of the invention is its salification by the
action of hydrochloric acid. For this, the reaction
mixture is diluted in a solvent in which the targeted
salified aniline derivative has little solubility and
hydrochloric acid is subsequently run into the reaction
mixture in order to precipitate the targeted aniline
derivative thus salified. The precipitate obtained is
subsequently filtered off.
The process of the invention makes possible the preparation of the envisaged aniline derivatives with a particularly advantageous degree of conversion of the reactants. The performance of the process of the invention varies, however, depending on the specific reaction conditions chosen; a person skilled in the art can easily find optimum reaction conditions by using the information given in the present description. Another advantage of the process of the invention is to allow the conversion of polyhalogenated
trifluoromethylbenzenes to aniline derivatives with a high yield.
This process is also particularly
advantageous in that it is highly selective, promoting the formation of polyhalogenated para-trifluoromethylanilines rather than polyhalogenated meta-trifluoromethylanilines.
An additional advantage of the process of the invention is that it makes possible reaction times which can be short; for example, reaction times of less than 10 hours, indeed even reaction times of less than 5 hours, can be employed.
The polyhalogenated trifluoromethylanilines which can be prepared by the process according to the
invention include 2,6-dichloro-4-trifluoro-
methylaniline, which is particularly advantageous as a
reaction intermediate in the preparation of compounds
used as insecticides.
The various examples which follow will make it possible to more fully illustrate the process of the invention and the advantages which are attached thereto; however, these examples do not in any way limit the scope of the invention. Example No. 1:
3,4,5-Trichloro-trifluoromethylbenzene (0.681 g, 2.73 mmol), lithium fluoride (7.1 mg, 0.273 mmol) and N-methylpyrrolidone (1.8 ml) are mixed in an autoclave. The autoclave is cooled to -95°C and
then ammonia (1.3 g, 76.4 mmol) is added. The autoclave is then heated at 250°C and with stirring for 4 h and is subsequently allowed to return to room temperature. The reaction product is extracted by washing with water and with dichloromethane and then the organic phase is evaporated, after having been dried. 0.453 g (1.97 mmol) of 2,6-dichloro-4-trifluoromethylaniline is obtained with a degree of conversion of the 3,4,5-trichloro-trifluoromethylbenzene of 97%, a ratio equal to 83/17 for the selectivity for 2,6-dichloro-para-
trifluoromethylaniline with respect to 2,6-dichloro-meta-trifluoromethylaniline and an 87% yield of 2,6-dichloro-para-trifluoromethylaniline. Example No. 2:
4-Bromo-3,5-dichloro-trifluoromethylbenzene (0.802 g, 2.73 mmol) and N-methylpyrrolidone (1.8 ml) are mixed in an autoclave. The autoclave is cooled to -95°C and then ammonia (1.3 g, 76.4 mmol) is added. The autoclave is then heated at 200°C and with stirring for 4 h and is subsequently allowed to return to room temperature.
The reaction product is extracted by washing with water and with dichloromethane and then the organic phase is evaporated, after having been dried.
0.428 g (1.86 mmol) of 2,6-dichloro-4-trifluoromethylaniline is obtained with a degree of conversion of the 4-bromo-3,5-dichloro-
trifluoromethylbenzene of 91%, complete selectivity for 2,6-dichloro-para-trifluoromethylaniline and a 68% yield of 2,6-dichloro-para-trifluoromethylaniline.
1. Process for the preparation of products of formula (I):
from reactants of formula (II):
in the presence of ammonia and optionally alkali metal halide at a
temperature of between 180 and 270°C and recovering the product by conventional manner.
2. Process as claimed in claim 1 for the preparation of products of
from reactants of formula (II):
in the presence of ammonia and of an alkali metal halide and at a temperature of between 180 and 270°C.
3. Process as claimed in claim 2, wherein the alkali metal halide is
present in a catalytic amount of between 1 to 50%, preferably between 5 to
20%, of the molar amount of reactant of formula (II).
4. Process as claimed in any one of claims 1 to 3, wherein the content of
water in the reaction mixture is such that the H2O/NH3 ratio is less than
80/100, preferably less than 20/100, more preferably less than 2/100.
5. Process as claimed in any one of claims 1 to 4, wherein a polar
organic solvent, preferably a monionic polar organic solvent, is used.
6. Process as claimed in any one of claims 1 to 5, wherein the solvent
employed is an N-alkylpyrrolidone, the alkyl radical of which preferably has
from 1 to 12 carbon atoms, more preferably N-methylpyrrolidone.
|Indian Patent Application Number||IN/PCT/2001/00525/DEL|
|PG Journal Number||07/2009|
|Date of Filing||18-Jun-2001|
|Name of Patentee||AVENTIS CROPSCIENCE SA|
|Applicant Address||55 AVENUE RENE CASSIN,F-69009 LYON,FRANCE|
|PCT International Classification Number||H01M 2/16|
|PCT International Application Number||PCT/FR99/03090|
|PCT International Filing date||1999-12-10|