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1. WO2011058576 - PROCÉDÉ POUR LA PRÉPARATION DE PERHALO-ALKYLANILINE POLYHALOGÉNÉE

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

PROCESS FOR PREPARING POLYHALOGENATED

PERHALOALKYLANILINE

FIELD OF THE INVENTION

The present invention relates to a process for preparing polyhalogenated perhaloalkyl-aniline which is useful as an intermediate for the synthesis of agrochemicals.

Particularly, the present invention envisages a process for preparing 2, 6-dichloro-4-trifluoromethyl-aniline.

BACKGROUND OF THE INVENTION AND PRIOR ART

p-Chlorobenzotrifluoride is easily available in commercial quantities and can be used typically as a source for grafting monomethylamine or dialkylamine onto a deactivated aromatic ring.

p-Chlorobenzotrifluoride can be aminated in an essentially non aqueous solvent medium which is nonreactive with the reactants in the presence of a catalytically effective amount of catalyst system comprising a selected copper compound and a selected alkaline halide salt at a predetermined pressure and at a temperature in the range of 150 to 240°C to produce p-aminobenzo-trifluoride. However, the conversion is low and the yields are correspondingly very less to accept it as an industrial process. Thus, the synthesis of p-aminobenzotrifluoride from p-chlorobenzotrifluoride is hitherto uneconomical at a commercial scale.

Aryl halides, especially activated aryl halides have been ammonolyzed using aqueous ammonia in the presence of a copper salt as a catalyst to obtain corresponding aromatic amines. However, this process is not applicable for the ammonolysis of p-chlorobenzotrifluoride as p-aminobenzotrifluoride is readily hydrolyzed to p-aminobenzoic acid or aniline in an aqueous medium. Ammonolysis of p-chlorobenzotrifluoride in a non-aqueous medium using copper compounds as a sole catalyst significantly reduces the hydrolysis problems but produces only a small amount of the desired p-aminobenzotrifluoride.

U.S.Patent No. 3,484,487 granted to James S. Dix discloses the use of copper chloride and non-polar organic solvents such as N-methylpyrrolidone, dimethylacetamide and dimethylformamide for the amination of aryl halides. These solvents are not suitable for the preparation of p-aminobenzotrifluoride since transamination occurs to a significant extent to form unwanted N,N-dimethylaminobenzotrifluoride.

The synthesis of anilines has generally been performed by hydrogenation of aromatic nitro compounds. However, the technique is not appropriate in the presence of substituents on the benzene ring which are sensitive to hydrogenolysis thus leading to a number of side reactions. Moreover, 4-nitro-benzotrifluoride is very difficult to make since nitration of benzotrifluoride yields significant quantities of the meta isomer.

p-Aminobenzotrifluoride can also be obtained by ammonolysis of p-chlorobenzotrifluoride in the presence of copper (I) chloride and potassium fluoride (J., Org. Chem. 44,4731 (1970)). However, the reaction conditions are too drastic, the conversions are low and the yields are, correspondingly very low for an industrial process.

U.S.Patent No. 4,096,185 discloses synthesis of p-aminobenzotrifluoride starting from p-chlorobenzotrifluoride in the presence of a catalyst combination containing alkali metal halides and copper compounds in the presence of non- aqueous solvents like alkanols, aromatic nitriles, aliphatic dinitriles, glycol ethers and the like at a superatmospheric pressure and at a temperature range of about 150 to 240°C.

U.S.Patent Nos.2, 194,925 and 2,194,926 disclose the reaction "of certain nitro-halo-benzotrifluorides with ammonia in a solvent medium and in the presence of a copper salt to produce, nitro-amino-benzotrifluorides.

British Patent No.1,164,223 granted to Farbenfabriken Bayer A.-G. describes the preparation of trifluoromethylaniline by hydrolysis of the corresponding trifluoromethylphenyl isocyanates.

Tetrahedron Letters, 1975, 143 (T.Cohen and J.G.Tirpak) describes Ullman coupling and ammonolysis of activated aryl halides catalyzed by copper compounds. However no alkali metal or ammonium halide is used for ammonolysis. Ammonolysis of aryl iodides and bromides is described which are known to aminate more readily than aryl chlorides.

U.S. Patent Nos. 5,401 ,882 granted to Jean -Marc Ricca, Lyons, France, discloses the synthesis of deactivated anilines by reacting 3,4-dichlorobenzotrifluoride with dimethylformamide in the presence of alkali metal hydroxide at temperature ranging between 150 to 250°C. The same

patent talk about chlorination of the dialkyl derivative followed by dealkylation of the dialkylaniline by chlorination under UV light or using stoichiometric quantity of pyridine salt and at elevated temperature.

Poly halogen ated trifluoromethylanilines are also made by ammonolysis of polyhalogenated benzotrifluoride in the presence of an alkaline halide at a temperature ranging between 150 to 350°C. WO 00/35851/2000 talks about synthesis of 2,6-Dichloro-4-trifluoromethylaniline starting from 3,4,5-trichloro-benzotrifluoride in the presence of alkaline fluorides like lithium fluoride and ammonia in the presence of N-methylpyrrolidone at 250°C to give 97% conversion and 87% selectivity. The main drawback of the above process is the synthesis of 3,4,5-trichlorobenzotrifluoride in high yield and purity. Chlorination of p-chlorobenzotrifluoride gives a mixture of 3,4,5-trichlorobenzotri fluoride in 72% GLC conversions, 3,4-dichloro and tetrachlorobenzotrifluoride. The process to get pure 3,4,5-isomer from this mixture by fractionation followed by crystallization is very tedious and industrially unviable. Moreover in-spite of using very pure intermediates, substantial amount of an undesired isomer (3-amino-4,5-dichlorobenzotrifluoride) is obtained .

Another approach to generate 3,4,5-trichlorobenzotrifluoride with a high yield and purity is to perform denitrochlorination of 4-chloro-3,5-dinitrobenzotfifluoride in the presence of a catalyst as described in GB Patent 2154581 A. Even though the process produces 3,4,5-trichlorobenzotrifluoide in high yield and purity, the reaction conditions are too drastic for an industrial process.

There is therefore felt a need for preparing polychlorinated p-trifluoromethylanilines, typically 2,6-dichloro-4-trifluoromethylaniline from easily available raw materials in a simple and economical manner at an industrial level, with high yields and purity.

OBJECTS OF THE INVENTION

An object of the present invention is to provide a process for the preparation of 2,6-dihalo-4-perhaloalkylaniline using commercially available raw materials.

Another object of the present invention is to provide a simple and commercially attractive process for the preparation of 2,6-dihalo-4-trifluoromethylaniline with high yield and purity.

SUMMARY OF THE INVENTION

In accordance with the present invention there is provided a process for the preparation of polyhalogenated perhaloalkylaniline which comprises the following steps:

a) reacting, in a polar solvent, a compound of formula (I)


Formula (1)

wherein:

Ri and R2 contain elements of halogen group respectively; and

R3 is a perhaloalkyl,

with ammonia, in the presence of an alkali halide at a temperature of about 200°C to about 300°C and a pressure of about 20 to about 50 kg/cm2 to form 2-halo-perhaloalkylaniline; and

b) reacting 2-halo-perhaloalkylaniline formed in step (a) with a halogenating agent to form a polyhalogenated perhaloalkylaniline.

In the preferred embodiment of the present invention, Rl and R2 are chlorine.

In a preferred embodiment of the present invention R3 is trifluoromethyl.

In the preferred embodiment of the present invention the polyhalogenated perhaloalkylaniline is 2,6-dichloro-4-trifluoromethylaniline.

Typically, the halogenating agent is at least one selected from a group consisting of chlorine, sulfuryl chloride, thionyl chloride and phosphorus pentachloride (PC15) .

Typically, the polar solvent is selected from a group consisting of N-methylpyrrolidone, N,N-dimethylimidazolidinone and dimethylsulfone, diphenyl sulfone .

The preferred solvent is N-methyl pyrrolidone.

Typically, the temperature at which the reaction takes place is in the range of about 235°C to about 250°C.

Typically, the reaction is conducted at a pressure of about 25 kg/cm2 to about 42 kg/cm .

Typically, the alkali metal halide is potassium fluoride.

Typically, the ammonia is anhydrous ammonia.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with the present invention a polyhalogenated perhaloalkylaniline compound is obtained by

(a) reacting a compound of the formula (I) with ammonia in the presence of an alkali halide and at a temperature of about 200°C to about 300°C and a pressure of about 20 to about 50 kg/cm to form 2-halo- perhaloalkylaniline and by

b) reacting 2-halo-perhaloalkylaniline formed in step (a) with a halogenating agent to form a polyhalogenated perhaloalkylaniline.


Formula (I)

Wherein R] and R2 contain elements of halogen group and R3 is a perhaloalkyl group.

In a preferred embodiment of the present invention K\ and R2 are chlorine, and R3 is trifluoromethyl. The compound of formula I is typically 3,4-dichloro benzotrifluoride.

According to a preferred embodiment of the present invention the polyhalogenated perhaloalkylaniline is 2,6-dichloro-4-trifluoromethyl aniline.

A process for preparing 2,6-dichloro-4-trifluoromethylaniline from 3,4-Dichloro benzotrifluoride is depicted in the reaction scheme below.


2,6-Dichloro-4-trifluoromethylaniline

Commercially available chlorobenzotrifluoride is selectively chlorinated to 3,4-dichlorobenzo-trifluoride with high yields and purity. Amination of 3,4-dichlorobenzotri fluoride with ammonia proceeds more easily as compared to that of p-chlorobenzotrifluoride. The resultant 2-chloro-4-trifluoromethylaniline is then further chlorinated to get the desired molecule 2,6-dichloro-4-trifluoromethyl aniline.

In a preferred embodiment of the present invention, 3,4-dichlorobenzotrifluoride is manufactured in high yields and purity by chlorination of commercially available p-chlorobenzotrifluoride. Ammonolysis of 3,4-dichlorobenzotrifluoride is easier and facile as compared to that of p-chlorobenzotrifluoride which gives much higher conversions as compared to that of p-chlorobenzotrifluoride. 3,4-Dichlorobenzotrifluoride is ammonolyzed with anhydrous ammonia in the presence of a polar solvent which is non reactive with the reactants under the reaction conditions. Ammonolysis is conducted in the presence of alkali halides under pressure at 20 to 50 kg/cm 2 , more preferably 25 to 42 kg/cm 2

and in a temperature range of about 200°C to about 300°C, more preferably in the temperature range of 235°C to 250°C. Catalytic amounts of copper compound may be used during ammonolysis.

The alkali halide is preferably potassium fluoride.

Anhydrous ammonia is used in excess of 5-6 m/m to start with. As the reaction proceeds, more ammonia is fed to maintain the reactor pressure and to minimize side reactions, which predominate at higher temperature due to lowering of ammonia concentrations.

In a preferred embodiment of the present invention, the solvent employed in the present process can be any solvent or a mixture of solvent, which do not decompose under the reaction conditions and is inert with respect to the reactants. Preferably the solvent used is a polar solvent. The polar solvent is selected from a group consisting of N-methyl pyrrolidine, Ν,Ν'-dimethylimidazolidinone, diphenyl sulfone and dimethylsulfone. N-

methylpyrrolidone is the solvent of choice as it does not interact with the reactants and at the same time it solubilises potassium fluoride.

According to the present invention, it is possible to prepare p-trifluoromethylaniline derivatives in a single step from the corresponding p-halobenzotri fluorides. However, results obtained are generally better when the starting material is dihalogenated or trihalogenated derivatives of p-benzotrifluoride.

In another aspect of the present invention, the halogenation of the substituted p-trifluoromethylaniline is carried out using halogenating agents like chlorine, thionyl chloride, sulfuryl chloride, PC15 and the like at temperatures ranging between 0°C to 100°C, preferably 0°C to 70°C. Among various halogens, the preferred halogen is chlorine unless a specific halogen is desired. The amount of halogenating agent used is limited to 10 to 50% excess, relative to the stoichiometric amount, preferably about 10-20% excess of the stoichiometric amount. Preferably, halogenation is done in chlorinated hydrocarbon solvents. The preferred solvents are carbon tetrachloride, dichloromethane, chlorobenzene, dichloroethane and o-dichlorobenzene.

The desired 2,6-dichloro-4-trifluoromethylaniline can be obtained with high purity by fractional distillation of the product post halogenation. Distilled product can be crystallized from a suitable solvent to achieve the desired quality.

The purity of the product is determined by gas chromatography.

The invention is illustrated with respect to the following examples which do not limit the scope of the invention in any way.

In the examples m/m means one gram mole of product obtained from 1 gram mole of substrate input.

Example- 1

N-methylpyrrolidone (1050 ml) was charged in an autoclave along with 102g anhydrous activated potassium fluoride and 377g 3,4-dichlorobenzotrifluoride. Ammonia gas (158 g) was passed from a pressure pot at ambient temperature. The content of the autoclave was heated to 245-250°C over a period of 2 hours to get reactor pressure of 30-32 kg/cm . Excess NH3 was fed from the pressure pot to maintain the reactor pressure at 38-40 kg/cm2 at 245-250°C liquid temperature. Reaction mixture was maintained at 245-250°C/38-40 kg/cm2 pressure for further 8 hours. Reaction mixture was cooled to ambient temperature, NH3 was vented and recovered. The reaction mass was filtered and fractionated to give 58.3% 2-chloro-4-trifluoromethylaniline and 9.2% 2-chloro-5-trifluoromethylaniline as other isomer with relative ratio of 87: 13. 25% of the starting material was recovered. The yield of 2-chloro-4-trifluoromethylaniline was 78% based on consumed 3 ,4-dichlorobenzotrifluoride.

Example- 2

N-methylpyrrolidone (815 ml) was charged in an autoclave along with 292 g of 3,4-dichlorobenzotrifluoride and 1 18g of calcined potassium fluoride. Ammonia gas (213 g) was fed into the autoclave. Ammonia gas (158 g) was

passed into the autoclave from a pressure pot at ambient temperature to achieve 38-40 kg/cm reactor pressure initially and the mixture in the autoclave was gradually heated to 245-250°C liquid temperature and further maintained at temperature 245-250°C and pressure 38-40 kg/cm for 6 hours by feeding ammonia gas to maintain the desired reactor pressure. The isomer ratio of 2-chloro-4-trifluoromethyl aniline to 2-chloro-5-trifluoromethyl aniline was 90: 10%. After treatment of reaction medium, 0.325 m/m of 3,4-dichlorobenzotrifluoride was recovered along with 0.508 m/m of 2-chloro-4-trifluoromethylaniline. The yield of 2-chloro-4-trifluoromethylaniline was 75.2% based on 3,4-dichlorobenzotrifiuoride consumed.

Example -3

3,4-Dichlorobenzotrifluoride (75.4 g) was added to 210 ml of N-methylpyrrolidone along with 30.45 g of calcined potassium fluoride & 1.73 g cuprous chloride and 6 g ammonia in an autoclave. Reaction mixture was maintained at 235°C and pressure of 25-26 kg/cm for 6 hrs. After work up and fractionation the yield of 2-chloro-4-trifluoiOmethyl aniline was 64% based on 3,4-dichlorobenzotrifluoride consumed

Example -4

3,4-Dichlorobenzotrifluoride (75.4 g) was added to 210 g of dimethylsulfone & 30.45 g of calcined potassium fluoride in an autoclave. The ammonia gas (1 to 1.2 m/m) was passed at 30°C. The reaction mixture was maintained at 235°C and 25-26 kg/cm2 for 6 hrs. After work up and fractionation the yield of 2-chloiO-4-trifluoromethylaniline was 84% based on 3,4-dichlorobenzotrifluoride consumed.

Example -5

3,4-Dichloi benzotrifluoride (75.4 g) was added to 210 ml of Ν,Ν'-dimethylimidazolidinone along with 30.45 g of calcined potassium fluoride in an autoclave. Ammonia gas (1 m/m) was passed and the resultant reaction mixture was heated to 235°C to get a pressure of 19 kg/cm2. Ammonia gas was further fed to maintain the pressure of the resultant mixture at 25-26 kg/cm for further 6 hrs at 235°C. After fractionation the yield of 2-chloro-4-trifluoromethyl aniline was 71.8% based on 3, 4-dichlorobenzotri fluoride consumed.

Example- 6

2-Chloro-4-trifluoromethylaniline (0.88m), 2-chloro-5-trifluoromethyl aniline (0.1 1 7 m) and 102 g of N-methyl pyrrolidone (NMP) was mixed with 500 ml chlorobenzene. Sulfuryl chloride (148.4 g) was added to the mixture at 55-60°C over a period of 4 hours and the reaction mixture was maintained at 55-60°C for 2 hours. Reaction medium on treatment with water and 5N NaOH followed by fractionation gave 0.84 m of 2,6-dichloro-4-trifluoromethylaniline, 95% yield on 2-chloro-4 rifluoromethylaniline.

Example- 7

A mixture (276 g) containing 2-chloi -4-trifluoromethylaniline, 2-chloro-5-trifluoromethylaniline, 72 g of NMP was mixed with 500 ml chlorobenzene. Sulfuryl chloride (135 g) was added to the mixture at 55-60°C liquid temperature over a period of 4 hours and the reaction temperature was maintained for further 2 hours. Additional 20.2 g of sulfuryl chloride was added to take the reaction to completion. Reaction medium on treatment and fractionation gave 0.809 m of 2,6-dichloro-4-trifluoiOmethylaniline, 94% yield on 2-chloro-4-trifluoromethylaniline.

Example-8

A mixture (740 g) containing 2-chloro-4-trifluoromethyaniline, 2-chloro-5-trifluoromethylaniline and 182 g of NMP was charged with 400 ml dichloroethane in to the reactor. It was then reacted with 430 g sulfuryl chloride at 55-60 °C over a period of 4 hrs & further maintained at 65-70°C for 2 hrs. The reaction mixture was worked up by adding water & treating with alkali, the organic layer was fractionated under reduced pressure to get 504.9 g of distilled 2,6-dichloro-4-trifluoromethylaniline.

Example-9

A mixture (270 g) containing 59.42% 2-chloro-4-tri fluoromethyl aniline, 12.37% 2-chloro-5-trifluoromethylaniline and 67 g of NMP was mixed with 210 ml chlorobenzene. It was chlorinated by passing 1.22m chlorine gas at 50-55 °C over a period of 8 hrs to 99 % conversion. The reaction mixture was worked up by adding water, treating the organic layer with alkali and the organic layer was fractionated under reduced pressure to get 92.5 g distilled 2,6-dichloro-4-trifluoromethylaniline. Yield was 49 % on 2-chloro-4-trifluoromethylaniline.

The numerical values of various parameters given in the specification are but approximations and slightly higher or slightly lower values of these parameters fall within the ambit and the scope of the invention.

While considerable emphasis has been placed herein on the specific steps of the preferred process, it will be highly appreciated that many steps can be made and that many changes can be made in the preferred steps without departing from the principles of the invention. These and other changes in the preferred steps of the invention will be apparent to those skilled in the art from the disclosures herein, whereby it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation.