DESC:FIELD OF THE INVENTION:
The present invention relates to a process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I). More particularly, the present invention relates to a process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-amino-3-nitrobenzotrifluoride (Formula II). Further, the present invention also relates to a process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-chloro-3-nitrobenzotrifluoride (Formula III).

BACKGROUND OF THE INVENTION:
3-chloro-4-amino-5-nitrobenzotrifluoride is a key intermediate for the synthesis of 2,6-dichloro-4-(trifluoromethyl) aniline (CN107311873B). Further, 2,6-dichloro-4-trifluoromethylaniline is a key intermediate for the synthesis of several pharmaceuticals, agrochemicals, and other important fine chemical products.
Numerous studies have already been carried out with the aim of developing processes for the preparation of 2,6-dichloro-4-trifluoromethylaniline.
The Chinese patent CN107311873B discloses a process for the preparation of 2,6-dichloro-4-trifluoromethylaniline from 3,4-dichloro-5-nitrobenzotrifluoride. In this process 3-chloro-4-amino-5-nitrobenzotrifluoride is obtained as an intermediate as a result of the amination of 3,4-dichloro-5-nitrobenzotrifluoride. The amination is carried out in the presence of ammonia gas (NH3). The problem with this process is that the yield is poor and the compound 3,4-dichloro-5-nitrobenzotrifluoride is not readily available.
EP0381010A2 discloses a process for the preparation of 4-chloro-3-nitro-benzotrifluoride from 4-amino-3-nitrobenzotrifluoride using aqueous ammonia at a temperature in the range of 80 to 150 oC in the presence of a copper catalyst.
Other processes reported in the literature widely use 4-trifluoromethyl aniline as a starting material for 2,6-dichloro-4-(trifluoromethyl) aniline.
However, there are several challenges with regards to the isolation of 4-trifluoromethylaniline (TFMA) such as it resinifies between 120 to 150°C in less than 2 hours. This property impedes the purification of these compounds, for example by distillation, since the boiling points even under reduced pressure are very close to the decomposition temperature. The distillates are often more unstable than the crude products. In the case of the storage of these compounds, for example as melts, precautions must be taken against overheating, especially since resinification takes place exothermically.
Further, the processes involving 4-trifluoromethylaniline as starting material results in the formation of impurities, such as polycondensates or heavy polychlorinated compounds, which makes it difficult to use 2,6-dichloro-4-trifluoromethylaniline in phenylpyrazole type pesticides without the prior purification.
Therefore, there is a need for a simple, environment friendly and cost effective alternate process for the synthesis of 2,6-dichloro-4-trifluoromethylaniline which avoids the use of 4-trifluoromethylaniline. Accordingly, the present invention provides a simple, novel, scalable and economical process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I). Further, the process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) of the instant invention obviates/minimizes the generation of waste which makes the process environmentally friendly.

OBJECTIVE OF THE INVENTION:
It is an objective of the present invention to ameliorate at least one of the drawbacks associated with the prior art.
Another objective of the present invention is to provide a process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-amino-3-nitrobenzotrifluoride (Formula II).
Yet another objective of the present invention is to provide a novel process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-chloro-3-nitrobenzotrifluoride (Formula III).
Yet another objective of the present invention is to provide a simple and cost-effective process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-chloro-3-nitrobenzotrifluoride (Formula III) which is suitable for industrial scale up.
Yet another object of the present invention is to provide a process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-chloro-3-nitrobenzotrifluoride (Formula III) which obviates the waste generation and hence is environmentally friendly.
Other objects and advantages of the present invention will be more apparent from the following description which is not intended to limit the scope of the present invention.

SUMMARY OF THE INVENTION
Accordingly, the present invention provides a process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-amino-3-nitrobenzotrifluoride (Formula II) comprising the step of chlorinating 4-amino-3-nitrobenzotrifluoride (Formula II) in the presence of a suitable chlorinating agent and a suitable solvent to afford 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I).
The suitable chlorinating agent is selected from the group consisting of hydrogen chloride, chlorine, N-chlorosuccinimide, oxalyl chloride, N-chlorobenzotriazole, sulfur-based chlorinating agents such as sulfuryl chloride, thionyl chloride, or the like; and phosphorus-based chlorinating agents such as phosphorus trichloride, phosphorus pentachloride, phosphorous oxychloride, or the like.
In one aspect, the present invention provides a process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-chloro-3-nitrobenzotrifluoride (Formula III) comprising the steps of:
a) reacting 4-chloro-3-nitrobenzotrifluoride (Formula III) with a suitable aminating reagent in the presence of a suitable solvent to afford 4-amino-3-nitrobenzotrifluoride (Formula II);
b) chlorinating 4-amino-3-nitrobenzotrifluoride (Formula II) of step (a) in the presence of a suitable chlorinating agent and a suitable solvent to afford 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I).
The suitable aminating reagent used in step (a) is ammonia.
Typically, ammonia may be in the form of aqueous, alcoholic or gaseous.
The suitable chlorinating agent is selected from the group consisting of hydrogen chloride, chlorine, N-chlorosuccinimide, oxalyl chloride, N-chlorobenzotriazole, sulfur-based chlorinating agents such as sulfuryl chloride, thionyl chloride, or the like; and phosphorus-based chlorinating agents such as phosphorus trichloride, phosphorus pentachloride, phosphorous oxychloride, or the like.
The suitable solvent is selected from the group consisting of aliphatic, alicyclic or aromatic halogenated hydrocarbons such as monochlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane or trichloroethane; aromatic hydrocarbon like toluene; ethers such as diethyl ether, diisopropyl ether, methyl tert- butyl ether, methyl tert- amyl ether, dioxane, tetrahydrofuran, 1, 2-dimethoxy ethane, 1, 2-diethoxy ethane or anisole; nitriles such as acetonitrile, propionitrile, n- or iso-butyronitrile or benzonitrile; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl formanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; sulfoxides such as dimethyl sulfoxide or sulfones such as sulfolane; alcohols such as methanol, ethanol, isopropanol, polyethylene glycols; acetates such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl benzoate, ethyl benzoate, and butyl benzoate; ketones like acetone; water or mixtures thereof.
The suitable solvent in step (a) and step (b) is the same or different.

DESCRIPTION OF THE INVENTION:
References in the specification to "one embodiment" or "an embodiment" means that a particular feature, structure, characteristic, or function described in connection with the embodiment is included in at least one embodiment of the invention. The appearances of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment.
References in the specification to “preferred embodiment” means that a particular feature, structure, characteristic, or function described in detail thereby omitting known constructions and functions for clear description of the present invention.
The foregoing description of specific embodiments of the present invention has been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the present invention to the precise forms disclosed and obviously many modifications and variations are possible in light of the above teaching.
The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure.
The use of the expression “at least” or “at least one” suggests the use of one or more elements or ingredients or quantities, as the use may be in the embodiment of the disclosure to achieve one or more of the desired objects or results.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skilled in the art. In case of conflict, the present document, including definitions will control. Preferred methods and materials are described below, although methods and materials similar or equivalent to those described herein can be used in practice or testing of the present invention. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting.
The terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures.
The singular forms “a,” “an” and “the” include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments “comprising,” “consisting of” and “consisting essentially of,” the embodiments or elements presented herein, whether explicitly set forth or not.
In line with the above defined objectives, the present invention provides a process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-amino-3-nitrobenzotrifluoride (Formula II) comprising the step of chlorinating 4-amino-3-nitrobenzotrifluoride (Formula II) in the presence of suitable chlorinating agent and a suitable solvent to afford 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I).
The process of the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-amino-3-nitrobenzotrifluoride (Formula II) is depicted in scheme I:

The process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-amino-3-nitrobenzotrifluoride (Formula II) comprises reacting 4-amino-3-nitrobenzotrifluoride (Formula II) with a suitable chlorinating reagent in the presence of a suitable solvent at a temperature in the range 10 to 100°C.

In one embodiment, the process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-amino-3-nitrobenzotrifluoride (Formula II) comprises reacting 4-amino-3-nitrobenzotrifluoride (Formula II) with a suitable chlorinating reagent such as chlorine in the presence of a suitable solvent such as dichloromethane, wherein the reaction is carried out at a temperature in the range 20 to 50°C.
In one embodiment of the present invention, the chlorination reaction is carried out at temperature in the range of 25 to 40°C.
The molar ratio of 4-chloro-3-nitrobenzotrifluoride (Formula III) and the suitable chlorinating reagent is in the range of 1:1 to 1:4.
The compound 4-chloro-3-nitrobenzotrifluoride (Formula III) is prepared from parachlorobenzotrifluoride.
In one aspect, the present invention provides a process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-chloro-3-nitrobenzotrifluoride (Formula III) comprising the steps of:
a) reacting 4-chloro-3-nitrobenzotrifluoride (Formula III) with a suitable aminating reagent in the presence of a suitable solvent to afford 4-amino-3-nitrobenzotrifluoride (Formula II);
b) chlorinating 4-amino-3-nitrobenzotrifluoride (Formula II) of step (a) in the presence of a suitable chlorinating agent and a suitable solvent to afford 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I).
The suitable aminating reagent used in step (a) is ammonia. Typically, ammonia may be in the form of aqueous, alcoholic or gaseous.
The suitable chlorinating agent is selected from the group consisting of hydrogen chloride, chlorine, N-chlorosuccinimide, oxalyl chloride, N-chlorobenzotriazole, sulfur-based chlorinating agents such as sulfuryl chloride, thionyl chloride, or the like; and phosphorus-based chlorinating agents such as phosphorus trichloride, phosphorus pentachloride, phosphorous oxychloride, or the like.
In one embodiment of the present invention, the suitable chlorinating agent is chlorine.
The suitable solvent is selected from the group consisting of aliphatic, alicyclic or aromatic halogenated hydrocarbons such as monochlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane or trichloroethane; aromatic hydrocarbon like toluene; ethers such as diethyl ether, diisopropyl ether, methyl tert- butyl ether, methyl tert- amyl ether, dioxane, tetrahydrofuran, 1, 2-dimethoxy ethane, 1, 2-diethoxy ethane or anisole; nitriles such as acetonitrile, propionitrile, n- or iso-butyronitrile or benzonitrile; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl formanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; sulfoxides such as dimethyl sulfoxide or sulfones such as sulfolane; alcohols such as methanol, ethanol, isopropanol, polyethylene glycols; acetates such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl benzoate, ethyl benzoate, and butyl benzoate; ketones like acetone; water or mixtures thereof.
In one embodiment of the present invention, the suitable solvent in step (a) and step (b) are same or different.
The process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-chloro-3-nitrobenzotrifluoride (Formula III) is depicted in scheme II:

The process for the preparation of 4-amino-3-nitrobenzotrifluoride (Formula II) from 4-chloro-3-nitrobenzotrifluoride (Formula III) comprises reacting 4-chloro-3-nitrobenzotrifluoride (Formula III) with a suitable aminating reagent in the presence of a suitable solvent, wherein the reaction is carried out at a temperature in the range of 80 to 150°C.
In one embodiment, the process for the preparation of 4-amino-3-nitrobenzotrifluoride (Formula II) from 4-chloro-3-nitrobenzotrifluoride (Formula III) comprises reacting 4-chloro-3-nitrobenzotrifluoride (Formula III) with a suitable aminating reagent such as ammonia at a temperature in the range 80 to 150°C at a pressure in the range of 6 to 12 bar.
Typically, ammonia may be in the form of aqueous, alcoholic or gaseous.
In one embodiment of the present invention, the amination reaction is carried out at a temperature in the range of 110 to 115 °C.
The molar ratio of 4-chloro-3-nitrobenzotrifluoride (Formula III) and the suitable aminating reagent is in the range of 1:5 to 1:15.
In one embodiment of the present invention, the molar ratio of 4-chloro-3-nitrobenzotrifluoride (Formula III) and the suitable aminating reagent is in the range of 1:5 to 1:12.
The process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-amino-3-nitrobenzotrifluoride (Formula II) comprises reacting 4-amino-3-nitrobenzotrifluoride (Formula II) with a suitable chlorinating reagent in the presence of a suitable solvent at a temperature in the range 10 to 60 °C.
In one embodiment of the present invention, the compound 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) is used for the synthesis of 2,6-dichloro-4-trifluoromethylaniline (Formula A) by using the process as disclosed in CN107311873B.
The process for the synthesis of 2,6-dichloro-4-trifluoromethylaniline (Formula A) is disclosed in the below Scheme 3:

In one embodiment of the present invention, the compound 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) is used as an intermediate for the synthesis of agrochemicals and pharmaceutical compounds.
The preparation processes as disclosed in the present invention are preferably carried out batch-wise. However, semi-continuous or continuous reaction passages, for instance under flow reaction conditions, are also possible.
The processes as disclosed in the present invention can be carried out in the absence of a solvent or in the presence of one or more suitable solvents. The optional solvent should be resistant against undesired side reactions, e.g., oxidation (i.e. a solvent will be preferred whose rate of oxidation is substantially lower than that of the compounds of present invention and suitable for suspending, or preferably dissolving the reactants).
Any person skilled in the art knows the best work-up of the reaction mixtures after the end of the respective reactions. In one embodiment, the work-up is usually carried out by isolation of the product by filtration, and optionally washing with a solvent, further optionally drying of the product if required.
The isolation of the reaction product can also be carried out by a technique which includes but is not limited to decantation, centrifugation, evaporation, ultrafiltration, liquid-liquid extraction, distillation, recrystallization, chromatography, and the like.
The process steps according to the invention are generally carried out under atmospheric pressure. Alternatively, however, it is also possible to work under reduced pressure or under pressure.

EXAMPLES
The invention is further illustrated with reference to the following examples. It is apparent to those skilled in the art that many modifications, both to materials, methods and various reaction parameters, may be practiced without departing from the scope of the invention. The starting materials according to the present invention are known compounds that are commercially available or can be prepared in a known manner. Following examples are given by way of illustration and therefore should not be construed to limit the scope of the invention.

Example 1 : Preparation of 4-amino-3-nitrobenzotrifluoride (Formula II)
(242 g) 25% aqueous ammonia and (100 gm) 4-chloro-3-nitrobenzotrifluoride (Formula III) was charged into an autoclave at 25±5°C. The reaction mixture was stirred for 8 hrs at 110 to 115°C and 8 to 10 bar. After completion of the reaction, the reaction mixture was cooled to 25±5°C. The reaction mixture was filtered at 25±5 °C and the resultant filtrate was washed twice with (100 gm) water to obtain wet solid (~85-90 g). The obtained wet solid was dried at 45 to 50°C in a vacuum tray dryer to obtain 4-amino-3-nitrobenzotrifluoride (Formula II) (85 g) (Yield- 92 %).
Example 2: Preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I)
4-amino-3-nitrobenzotrifluoride (Formula II) (100 gm) and dichloromethane (400 g) were charged in the reaction kettle at 25±5°C. To this reaction mixture, chlorine was purged at 35±5°C. After completion of the reaction, the resulting mixture was cooled, washed with water (100 mL) and the dichloromethane layer was separated. The resulting filtrate was neutralized with sodium bicarbonate up to 7-8 pH of dichloromethane and again washed with water (100 mL) and the dichloromethane layer was separated. The dichloromethane layer was concentrated under vacuum to obtain crude reaction mass (116 g). Crystallization was carried out to obtain pure 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) (74 g) (Yield- ~ 64%).
Example 3: Preparation of 2,6-dichloro-4-trifluoromethylaniline (CN107311873B)
Add 1200 kg of 3-chloro-4-amino-5-nitrotrifluorotoluene to the chlorination kettle, seal the reactor, replace with nitrogen, start stirring, gradually heat up to 200 ° C, gradually introduce chlorine, control the reaction temperature at 70-80 ° C, when the introduction amount reaches 407 kg, sample and detect 0.4% of 3,4-dichloro-5-nitrotrifluorotoluene through a sampling tube, cool to below 30 ° C, vent the chlorine to the tail gas recovery device, add 200 kg of ammonia water * 4 water to the reactor for washing, dehydrate under reduced pressure, and obtain 1090 kg of material by reduced pressure distillation (the obtained 2,6-dichloro-4-trifluoromethylaniline has a content of 99.5%, a moisture content of 0.5%, and a yield of 95.3%).
The embodiments were chosen and described in order to best explain the principles of the present invention and its practical application, to thereby enable others, skilled in the art to best utilize the present invention and various embodiments with various modifications as are suited to the particular use contemplated.
It is understood that various omissions and substitutions of equivalents are contemplated as circumstance may suggest or render expedient, but such are intended to cover the application or implementation without departing from the scope of the present invention.
,CLAIMS:WE CLAIM:
1. A process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-amino-3-nitrobenzotrifluoride (Formula II) comprising the step of chlorinating 4-amino-3-nitrobenzotrifluoride (Formula II) in the presence of suitable chlorinating agent and a suitable solvent to afford 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I);
.
2. A process for the preparation of 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I) from 4-chloro-3-nitrobenzotrifluoride (Formula III) comprising the steps of:
a) reacting 4-chloro-3-nitrobenzotrifluoride (Formula III) with a suitable aminating reagent in the presence of a suitable solvent to afford 4-amino-3-nitrobenzotrifluoride (Formula II);
b) chlorinating 4-amino-3-nitrobenzotrifluoride (Formula II) of step (a) in the presence of a suitable chlorinating agent and a suitable solvent to afford 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I);
.
3. The process as claimed in claim 2, wherein said process further comprises the synthesis of 2,6-dichloro-4-trifluoromethylaniline (Formula A) from 3-chloro-4-amino-5-nitrobenzotrifluoride (Formula I).
4. The process as claimed in claim 1 and 2, wherein the molar ratio of 4-chloro-3-nitrobenzotrifluoride (Formula III) and the suitable chlorinating reagent is in the range of 1:1 to 1:4.
5. The process as claimed in claim 1 and 2, wherein said suitable chlorinating agent is selected from the group consisting of hydrogen chloride, chlorine, N-chlorosuccinimide, oxalyl chloride, N-chlorobenzotriazole, sulfur-based chlorinating agents selected from sulfuryl chloride, thionyl chloride; and phosphorus-based chlorinating agents selected from phosphorus trichloride, phosphorus pentachloride or phosphorous oxychloride,.
6. The process as claimed in claim 1 and 2, wherein said chlorination reaction is carried out at a temperature in the range 10 to 100°C.
7. The process as claimed in claim 2, wherein the molar ratio of 4-chloro-3-nitrobenzotrifluoride (Formula III) and the suitable aminating reagent is in the range of 1:5 to 1:15 and said amination reaction is carried out at a temperature in the range of 80 to 150 °C and 6 to 12 bar.
8. The process as claimed in claim 2, wherein said suitable aminating reagent used in step (a) is ammonia and is in the form of aqueous, alcoholic or gaseous.
9. The process as claimed in claim 1 and 2, wherein said suitable solvent in step (a) and step (b) is the same or different.
10. The process as claimed in claim 9, wherein said suitable solvent is selected from the group consisting of aliphatic, alicyclic or aromatic halogenated hydrocarbons selected from monochlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane or trichloroethane; aromatic hydrocarbon selected from selected from toluene; ethers selected from diethyl ether, diisopropyl ether, methyl tert- butyl ether, methyl tert- amyl ether, dioxane, tetrahydrofuran, 1, 2-dimethoxy ethane, 1, 2-diethoxy ethane or anisole; nitriles selected from acetonitrile, propionitrile, n- or iso-butyronitrile or benzonitrile; amides selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl formanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; sulfoxides selected from dimethyl sulfoxide or sulfones selected from sulfolane; alcohols selected from methanol, ethanol, isopropanol, polyethylene glycols; acetates selected from methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl benzoate, ethyl benzoate, and butyl benzoate; ketones selected from acetone; water or mixtures thereof.

Dated this 09th day of December 2023.
For AARTI INDUSTRIES LTD

MAHURKAR ANAND GOPALKRISHNA
IN/PA-1862
(Agent for Applicant)