"a process for the preparation of ARYL halides"

Abstract

The present invention provides the process for the preparation of substituted aryl halide compound of Formula (I) from substituted aryl amine compound of Formula (II) in the absence of catalyst wherein, X, n and R1 are as defined herein.

Description

[0001] “A PROCESS FOR THE PREPARATION OF ARYL HALIDES”

[0002] FIELD OF THE INVENTION:

[0003] The present invention relates to a process for the preparation of substituted aryl halide compound of Formula (I). More particularly, the present invention relates to a process for the preparation of substituted aryl halide compound of Formula (I) from substituted aryl amine compound of Formula (II).

[0004] BACKGROUND OF THE INVENTION:

[0005] Aryl halides are widely found in natural products, used to prepare pharmaceutical compounds, and have wide application in biological activity modulation and material chemistry. They have played a critical role in organic synthesis, especially in transition metal catalyzed coupling reactions such as Suzuki cross-coupling and Heck-type reactions and also in the preparation of organometallic reagents. Further, aryl halides are not only important structural units of chemical products such as medicines, pigments, liquid crystal materials and the like, but also important structural units of many natural compounds.

[0006] Therefore, the development of the aryl halide synthetic route has important research significance and practical value. Traditionally, aryl halide synthesis method mainly depends on halogen as a reagent, these reactions generate hydrogen halide gas as byproducts, therefore the complexity of the reaction process and posttreatment is further increased.

[0007] The synthesis of aryl halides by in situ oxidation using inorganic halides as halogen sources is an important new approach to aryl halogenation, which requires oxidants, however the reactions are carried out at harsh reaction conditions and results in poor reaction selectivity, although the application of halogens is avoided.

[0008] One of the most popular methods for the synthesis of aryl halides from aromatic amines is the Sandmeyer reaction. In addition, a successful method has been reported for the halogenation of aromatic amines with alkyl nitrites in the presence of anhydrous copper salts (II) via substituted deamination reactions.

[0009] The Korean Patent Application KR20120010353A discloses a method of synthesis for aromatic halides from aromatic amines through the diazotizationhalogenation reaction to form arenediazonium tosylate salts in the presence of copper salt as a catalyst. The drawback of this method is handling the arenediazonium tosylate salts and also the use of copper salt as a catalyst. However, this process provides a low yield of 88% using catalyst.

[0010] Similarly, the Chinese Patent Application CN106905104A discloses the process for the preparation of 2-bromo-5-fluorobenzotrifluoride from o- trifluoromethylaniline through the similar diazotization-halogenation route using the cuprous bromide as catalyst with low yield of 91%.

[0011] However, the problem associated with this process is the handling of copper containing waste.

[0012] Also, other conventional processes use metal catalysts such as copper bromide, which is responsible for generating huge quantities of effluent containing metallic impurities and other process impurities. These metallic impurities in the product are creating problems in the final product of aromatic halides which go into electronic applications.

[0013] The conventionally developed techniques cause environmental problems using a large amount of catalysts such as copper salts as reaction reagents. Therefore, there is a need to develop a process for the preparation of aromatic halides which at least partially obviates one problem of prior art processes, such as requirement of use of catalyst, large waste or residue formation, and costeffectiveness.

[0014] The inventors of the represent invention surprisingly and unexpectedly found that the process of preparing aromatic halide can be carried out without using copper based catalyst. Accordingly, the present inventors developed a process for simple and effective diazotization of aromatic amines by using the properties of such diazonium salts. The diazotization is carried out using a diazotizing agent, optionally in the presence of acid and the subsequent reaction of halogenation reagents in the absence of copper based catalyst.

[0015] OBJECTIVE OF THE INVENTION:

[0016] It is an objective of the present invention to ameliorate at least one of the drawbacks associated with the prior art.

[0017] The objectives of the present invention are described herein below:

[0018] An objective of the present invention is to provide a process for the preparation of substituted aryl halide compound of Formula (I) from substituted aryl amine compound of Formula (II).

[0019] Another objective of the present invention is to provide a cost-effective process for the preparation of substituted aryl halide compound of Formula (I) having improved yield and purity.

[0020] Another objective of the present invention is to provide a cost-effective process for the preparation of substituted aryl halide compound of Formula (I) which is devoid of using copper based catalyst.

[0021] Yet another objective of the present invention is to provide a process for the preparation of substituted aryl halide compound of Formula (I) which obviates the use of copper based catalyst and provides improved yield of more than 95%.

[0022] Yet another objective of the present invention is to provide a process for the preparation of the substituted aryl halide compound of Formula (I) in absence of copper based catalyst which gives improved yield of the substituted aryl halide compound of Formula (I) with yield more than 95% and purity more than 99% reducing the des-halo and di-halo impurities formation. One specific objective of the present invention is to provide a process for the preparation of 2-bromo-benzo trifluoride (i) from 2-amino benzotrifluoride (ii).

[0023] Other objects and advantages of the present invention will be a more apparent description which is not intended to limit the scope of the present invention.

[0024] SUMMARY OF THE INVENTION:

[0025] First aspect of the present invention is to provide a process for the preparation of substituted aryl halide compound of Formula (I) comprising the step of: a) reacting substituted aryl amine compound of Formula (II) with a suitable diazotizing reagent optionally in the presence of suitable acid at a temperature in the range of 5 to 50 °C to obtain aryl diazonium salt of substituted aryl amine compound of Formula (II); b) reacting the aryl diazonium salt of substituted aryl amine compound of Formula (II) of step (a) with a suitable halogenating reagent at a temperature in the range of 20 to 120°C, optionally in presence of suitable solvent to obtain substituted aryl halide compound of Formula (I).

[0026] As depicted in scheme 1 below:

[0027] Formula (IS) Formula rt)

[0028] Scheme: 1 wherein,

[0029] X is fluorine, chlorine or bromine;

[0030] R1is selected from the group consisting of halogen, amino, hydroxy, alkyl, alkenyl, alkoxy, haloalkyl, haloalkoxy, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted cycloalkyl and substituted or unsubstituted cycloalkyloxy; n is 1 to 5.

[0031] Another aspect of the present invention is to provide a process for the preparation of substituted aryl halide compound of Formula (I) comprising the step of: a) reacting substituted aryl amine compound of Formula (II) with a suitable diazotizing reagent optionally in the presence of suitable acid at a temperature in the range of 5 to 50 °C to obtain aryl diazonium salt of substituted aryl amine compound of Formula (II); b) reacting the aryl diazonium salt of substituted aryl amine compound of Formula (II) of step (a) with a suitable halogenating reagent at a temperature in the range of 20 to 120°C, optionally in presence of suitable solvent to obtain substituted aryl halide compound of Formula (I).

[0032] As depicted in scheme 1 below:

[0033] Formula (10 Formula (Q

[0034] Scheme: 1 wherein,

[0035] X is fluorine, chlorine or bromine;

[0036] R1is selected from the group consisting of halogen or amino; n is 1 to 5.

[0037] Yet another aspect of the present invention is to provide a process for the preparation of substituted aryl halide compounds of Formula (I) which is carried out without the use of catalysts, particularly copper based catalysts. Yet another aspect of the present invention is to provide a process for the preparation of the substituted aryl halide compound of Formula (I) in absence of copper based catalyst which gives improved yield of the substituted aryl halide compound of Formula (I) with yield more than 95% and purity more than 99%.

[0038] Yet another aspect of the present invention is to provide a process for the preparation of the substituted aryl halide compound of Formula (I) in absence of copper based catalyst which gives improved yield of the substituted aryl halide compound of Formula (I) with yield more than 95% and purity more than 99% with des-halo impurity less than 0.02% and di-halo impurity less than 0.2%.

[0039] DETAILED DESCRIPTION OF THE INVENTION

[0040] References in the specification to “preferred embodiment” means that a particular feature, structure, characteristic, or function is described in detail thereby omitting known constructions and functions for clear description of the present invention.

[0041] 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.

[0042] 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.

[0043] When a group is described as being “unsubstituted or substituted” if substituted, the substituent(s) may be selected from one or more of the indicated substituents. If no substituents are indicated, it is meant that the indicated “optionally substituted” or “substituted” group may be substituted with one or more group(s) (such as 1, 2 or 3) individually and independently selected from hydrogen, halogen, cyano, hydroxy, alkyl, alkoxy, haloalkyl, haloalkoxy, aryl, aryloxy, cycloalkyl and cycloalkyloxy. The meaning of various terms used in the description shall now be illustrated.

[0044] The term substituted or unsubstituted “aryl” is understood as meaning aromatic hydrocarbon radicals containing from 6 to 14 carbon atoms depending on the number of carbon atoms in one, two or three rings.

[0045] The term “alkyl”, used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched Ci to Cio alkyl, most preferably Ci to Cf> alkyl. Non- limiting examples of alkyl include methyl, ethyl, propyl, 1 -methylethyl, butyl, 1 -methylpropyl, 2-methylpropyl, 1,1 -dimethylethyl, pentyl, 1 -methylbutyl, 2-methylbutyl, 3 -methylbutyl, 2,2-dimethylpropyl, 1- ethylpropyl, hexyl, 1,1 -dimethylpropyl, 1,2-dimethylpropyl, 1 -methylpentyl, 2- methylpentyl, 3 -methylpentyl, 4-methylpentyl, 1,1 -dimethylbutyl, 1,2- dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3- dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2- trimethylpropyl, 1 -ethyl- 1 -methylpropyl and l-ethyl-2-methylpropyl or the different isomers. If the alkyl is at the end of a composite substituent, as, for example, in alkylcycloalkyl, the part of the composite substituent at the start, for example the cycloalkyl, may be mono- or poly substituted identically or differently and independently by alkyl. The same also applies to composite substituents in which other radicals, for example alkenyl, alkynyl, hydroxy, halogen, carbonyl, carbonyloxy and the like, are at the end.

[0046] The term “alkenyl”, used either alone or in compound words includes straight-chain or branched C2 to Cio alkenes, most preferably C2 to Cf> alkenes. Nonlimiting examples of alkenyl include ethenyl, 1 -propenyl, 2-propenyl, 1- methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1 -methyl- 1 -propenyl, 2-methyl-l- propenyl, l-methyl-2 -propenyl, 2-methyl-2-propenyl, 1 -pentenyl, 2-pentenyl, 3- pentenyl, 4-pentenyl, 1 -methyl- 1-butenyl, 2-methyl- 1-butenyl, 3 -methyl- 1-butenyl, l-methyl-2-butenyl, 2-methyl-2-butenyl and the different isomers. “Alkenyl” also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl. This definition also applies to alkenyl as a part of a composite substituent, for example haloalkenyl and the like, unless defined specifically elsewhere. Non-limiting examples of alkynes include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, l-methyl-2-propynyl, 1 -pentynyl, 2-pentynyl, 3- pentynyl, 4-pentynyl, l-methyl-2-butynyl, l-methyl-3-butynyl, 2-methyl-3- butynyl, 3 -methyl- 1-butynyl, l,l-dimethyl-2-propynyl, l-ethyl-2-propynyl, 1- hexynyl, 2-hexynyl and the different isomers. This definition also applies to alkynyl as a part of a composite substituent, for example haloalkynyl etc., unless specifically defined elsewhere.

[0047] The term “alkynyl” can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.

[0048] The term “cycloalkyl” means alkyl closed to form a ring. Non-limiting examples include cyclopropyl, cyclopentyl and cyclohexyl. This definition also applies to cycloalkyl as a part of a composite substituent, for example cycloalkylalkyl etc., unless specifically defined elsewhere.

[0049] The term “cycloalkoxy”, “cycloalkenyloxy” and the like are defined analogously. Non-limiting examples of cycloalkoxy include cyclopropyloxy, cyclopentyloxy and cyclohexyloxy. This definition also applies to cycloalkoxy as a part of a composite substituent, for example, cycloalkoxy alkyl etc., unless specifically defined elsewhere.

[0050] The term “cycloalkyloxy” as used herein, means cycloalkyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. Representative examples of cycloalkyloxy include, but are not limited to, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, and the like.

[0051] The term “aryloxy,” as used herein, represents an aryl group attached to the parent molecular moiety through an oxygen atom such as phenyloxy, 4- methylphenoxy, naphthyloxy, and the like.

[0052] The term “halogen”, either alone or in compound words such as “haloalkyl”, includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Non- limiting examples of “haloalkyl” include chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1 -chloroethyl, 1 -bromoethyl, 1- fluoroethyl, 2- fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2- fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2- trichloroethyl, pentafluoroethyl, l,l-dichloro-2,2,2-trifluoroethyl, and 1,1,1- trifluoroprop-2-yl. This definition also applies to haloalkyl as a part of a composite substituent, for example, haloalkylaminoalkyl, etc., unless specifically defined elsewhere. The terms “haloalkenyl”, “haloalkynyl” are defined analogously except that, instead of alkyl groups, alkenyl and alkynyl groups are present as a part of the substituent. The term “haloalkoxy” means straight-chain or branched alkoxy groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above. Non-limiting examples of haloalkoxy include chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1 -chloroethoxy, 1 -bromoethoxy, 1 -fluoroethoxy, 2-fluoroethoxy, 2, 2 -difluoroethoxy, 2,2,2-trifluoroethoxy, 2- chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and l,l,l-trifluoroprop-2-oxy. This definition also applies to haloalkoxy as a part of a composite substituent, for example, haloalkoxyalkyl etc., unless specifically defined elsewhere

[0053] The term “alkoxy” used either alone or in compound words included Ci to Cio alkoxy, most preferably Ci to Cf> alkoxy. Examples of alkoxy include methoxy, ethoxy, propoxy, 1 -methylethoxy, butoxy, 1 -methylpropoxy, 2-methylpropoxy,

[0054] 1.1- dimethylethoxy, pentoxy, 1 -methylbutoxy, 2-methylbutoxy, 3-methylbutoxy,

[0055] 2.2-dimethylpropoxy, 1 -ethylpropoxy, and the different isomers. This definition also applies to alkoxy as a part of a composite substituent, for example, haloalkoxy, alkynylalkoxy and the like, unless specifically defined elsewhere. 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.

[0056] 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.

[0057] 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.

[0058] The numerical values mentioned for the various physical parameters, dimensions or quantities are only approximations and it is envisaged that the values higher / lower than the numerical values assigned to the parameters, dimensions or quantities fall within the scope of the disclosure, unless there is a statement in the specification specific to the contrary.

[0059] 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.

[0060] One embodiment of the present invention is to provide a process for the preparation of substituted aryl halide compound of Formula (I);

[0061]

[0062] Formula di wherein,

[0063] X is fluorine, chlorine or bromine;

[0064] R1is selected from the group consisting of halogen, amino, hydroxy, alkyl, alkenyl, alkoxy, haloalkyl, haloalkoxy, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted cycloalkyl and substituted or unsubstituted cycloalkyloxy; n is 1 to 5 comprising the step of: a) reacting substituted aryl amine compound of Formula (II);

[0065] Formula dh wherein, n and R1are as defined above; with a suitable diazotizing reagent optionally in the presence of suitable acid at a temperature in the range of 5 to 50°C to obtain aryl diazonium salt of substituted aryl amine compound of Formula (II); b) reacting the aryl diazonium salt of substituted aryl amine compound of Formula (II) of step (a) with a suitable halogenating reagent at a temperature in the range of 20 to 120°C, optionally in presence of suitable solvent to obtain substituted aryl halide compound of Formula (I).

[0066] Non-limiting examples of the suitable diazotizing reagent used in step (a) in accordance with the present invention include sodium nitrite, calcium nitrite, potassium nitrite, alkyl nitrite, nitrosyl sulfuric acid, or combination thereof.

[0067] Non-limiting examples of the suitable halogenating reagent used in step (b) are selected from suitable brominating reagents, suitable chlorinating reagents, or suitable fluorinating reagents.

[0068] Non-limiting examples of the suitable halogenating reagents in accordance with the present invention include bromine, hydrogen bromide, -bromo- succinimide (NBS), cupric bromide, sodium bromide, potassium bromide, bromine monochloride, hydrogen chloride, N-chlorosuccini mide, sodium hypochlorite, tertbutyl hypochlorite, hydrofluoric acid, tetrafluoroboric acid (HBF4), hydrogen fluoride, cesium fluoride, potassium fluoride, ammonium fluoride, sodium fluoride, or combination thereof.

[0069] Typically, the suitable acid in accordance with the present invention is selected from mineral acid or organic acid.

[0070] Non-limiting examples of the suitable mineral acid in accordance with the present invention include hydrochloric acid, sulfuric acid, oleum, or combination thereof.

[0071] Non-limiting examples of the suitable organic acid in accordance with the present invention include formic acid, acetic acid, trifluoroacetic acid, chlorosulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, or combination thereof.

[0072] In one embodiment of the present invention, the suitable acid is added in a continuous or lotwise manner.

[0073] The process for the preparation of substituted aryl halide compound of Formula (I) wherein the diazotization reaction in step (a) is carried out at a reaction temperature in the range of 5 to 50°C, preferably at a temperature ranging from 10 to 35 °C; with reaction time in the range of 0.5 hour to 5 hours, preferably for 1 hour to 4 hours.

[0074] The process for the preparation of substituted aryl halide compound of Formula (I) wherein the halogenation reaction in step (b) is carried out at a reaction temperature in the range of 20 to 120°C, preferably at a temperature ranging from 30 to 70°C; with reaction time in the range of 0.5 hour to 6 hours, preferably for 1 hour to 4 hours.

[0075] The halogenation reaction is carried out in the presence or absence of a solvent. When halogenation is carried out in the presence of solvent, the nonlimiting examples of solvents suitable for the halogenation reaction include aliphatic, alicyclic or aromatic halogenated hydrocarbons such as monochlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane, trichloroethane, toluene, diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 1, 2-dimethoxy ethane, 1, 2-diethoxy ethane, anisole, acetonitrile, propionitrile, n- or iso-butyronitrile or benzonitrile, AW-di methyl formamide, N,N- dimethylacetamide, Wmethyl formanilide, Wmethylpyrrolidone, hexamethylphosphoric triamide, dimethyl sulfoxide, sulfolane, methanol, ethanol, isopropanol, polyethylene glycols, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl benzoate, ethyl benzoate, butyl benzoate, acetone, acetic acid, water, or mixtures thereof.

[0076] In one embodiment, the process for the preparation of substituted aryl halide compound of Formula (I) from substituted aryl amine compound of Formula (II) is depicted in scheme 1 below:

[0077]

[0078] Formula H Fo-rnwla (I)

[0079] Scheme: 1

[0080] The definition of X, n and R1are as defined before.

[0081] In one embodiment, the molar ratio of substituted aryl amine compound of Formula (II) and a suitable diazotizing reagent is in the range of 1:0.5 to 1: 1.5.

[0082] In one embodiment, the molar ratio of substituted aryl amine compound of Formula (II) and a suitable halogenating reagent is in the range of 1: 1 to 1:2.

[0083] In accordance with the process of the present invention, the substituted aryl halide compound of Formula (I) is obtained in the yield more than 95%.

[0084] In accordance with the process of the present invention, the substituted aryl halide compound of Formula (I) is having the purity of more than 99%.

[0085] In another embodiment, the present invention provides a process for the preparation of 2-bromo-benzotrifluoride compound of Formula (i) from 2-amino benzotrifluoride compound of Formula (ii) comprising the step of: a) reacting 2-amino benzotrifluoride compound of Formula (ii) with a suitable diazotizing reagent optionally in the presence of suitable acid at a temperature in the range of 5 to 50°C to obtain diazonium salt of 2-amino benzotrifluoride compound of Formula (ii); b) reacting the diazonium salt of 2-amino benzotrifluoride compound of Formula (ii) of step (a) with a suitable brominating reagent at a temperature in the range of 20 to 120°C, optionally in presence of suitable solvent to obtain 2-bromo-benzotrifluoride compound of Formula (i) as depicted in scheme 2 below.

[0086]

[0087] Formula lit) 1 ormula (f)

[0088] Scheme: 2

[0089] In yet another embodiment, the present invention provides a process for the preparation of 2-chloro-benzotrifluoride compound of Formula (iii) from 2-amino benzotrifluoride compound of Formula (iv) comprising the step of: a) reacting 2-amino benzotrifluoride compound of Formula (iv) with a suitable diazotizing reagent optionally in the presence of suitable acid at a temperature in the range of 5 to 50°C to obtain diazonium salt of 2-amino benzotrifluoride compound of Formula (iv); b) reacting the diazonium salt of 2-amino benzotrifluoride compound of Formula (iv) of step (a) with a suitable chlorinating reagent at a temperature in the range of 20 to 120°C, optionally in presence of suitable solvent to obtain 2-chloro-benzotrifluoride compound of Formula (iii) as depicted in scheme 3 below.

[0090] Scheme: 3 In yet another embodiment, the present invention provides a process for the preparation of 2-fluoro-benzotrifluoride compound of Formula (v) from 2-amino benzotrifluoride compound of Formula (vi) comprising the step of: a) reacting 2-amino benzotrifluoride compound of Formula (vi) with a suitable diazotizing reagent optionally in the presence of suitable acid at a temperature in the range of 5 to 50°C to obtain diazonium salt of 2-amino benzotrifluoride compound of Formula (vi); b) reacting the diazonium salt of 2-amino benzotrifluoride compound of Formula (vi) of step (a) with a suitable fluorinating reagent at a temperature in the range of 20 to 120°C, optionally in presence of suitable solvent to obtain 2-fluoro-benzotrifluoride compound of Formula (v) as depicted in scheme 4 below.

[0091] Scheme: 4

[0092] The inventors of the present invention surprisingly found a process which obviates the use of copper based catalyst and surprisingly gives improved yield of more than 95% with purity more than 99% reducing the des-halo and di-halo impurities formation and improves the yield of the substituted aryl halide compound of Formula (I) as depicted in the scheme 1, 2, 3, and 4.

[0093] In one embodiment of the present invention is to provide a process for the preparation of the substituted aryl halide compound of Formula (I) in absence of copper based catalyst which gives improved yield of the substituted aryl halide compound of Formula (I) with yield more than 95% and purity more than 99%. In one embodiment of the present invention is to provide a process for the preparation of the substituted aryl halide compound of Formula (I) in absence of copper based catalyst which gives improved yield of the substituted aryl halide compound of Formula (I) with yield more than 95% and purity more than 99% with des-halo impurity less than 0.02% and di-halo impurity less than 0.2%.

[0094] Non-limiting examples of the suitable diazotizing agent used in step (a) in accordance with the present invention include sodium nitrite, calcium nitrite, potassium nitrite, alkyl nitrite, nitrosyl sulfuric acid or combination thereof.

[0095] Non-limiting examples of the suitable halogenating reagents used in step (b) are selected from suitable brominating reagents, suitable chlorinating reagents, or suitable fluorinating reagents.

[0096] Non-limiting examples of the suitable halogenating reagents in accordance with the present invention include bromine, hydrogen bromide, -bromo- succinimide (NBS), cupric bromide, sodium bromide, potassium bromide, bromine monochloride, hydrogen chloride, N-chlorosuccini mide, sodium hypochlorite, tertbutyl hypochlorite, hydrofluoric acid, tetrafluoroboric acid (HBF4), hydrogen fluoride, cesium fluoride, potassium fluoride, ammonium fluoride, sodium fluoride, or combination thereof.

[0097] Typically, the suitable acid in accordance with the present invention is selected from mineral acid or organic acid.

[0098] Non-limiting examples of the suitable mineral acid in accordance with the present invention include hydrochloric acid, sulfuric acid, oleum, or combination thereof.

[0099] Non-limiting examples of the suitable organic acid in accordance with the present invention include formic acid, acetic acid, trifluoroacetic acid, chlorosulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, or combination thereof.

[0100] In one embodiment of the present invention, the suitable acid is added in a continuous or lotwise manner. The process for the preparation of substituted aryl halide compound of Formula (I) wherein the diazotization reaction in step (a) is carried out at a reaction temperature in the range of 5 to 50°C, preferably at a temperature ranging from 10 to 35 °C; with reaction time in the range of 0.5 hour to 5 hours, preferably for 1 hour to 4 hours.

[0101] The process for the preparation of substituted aryl halide compound of Formula (I) wherein the halogenation reaction in step (b) is carried out at a reaction temperature in the range of 20 to 120°C, preferably at a temperature ranging from 30 to 70°C; with reaction time in the range of 0.5 hour to 6 hours, preferably for 1 hour to 4 hours.

[0102] In one embodiment, the molar ratio of substituted aryl amine compound of Formula (II) and a suitable diazotizing reagent is in the range of 1:0.5 to 1: 1.5.

[0103] In one embodiment, the molar ratio of substituted aryl amine compound of Formula (II) and a suitable halogenating reagent is in the range of 1: 1 to 1:2.

[0104] In one embodiment, the present invention is to provide a process for the preparation of substituted aryl halide compound of Formula (I) which obviates the use of copper based catalyst and provides improved yield of more than 95% with purity more than 99% as depicted in the scheme 1, 2, 3, and 4.

[0105] 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.

[0106] 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.

[0107] Various features and embodiments of the present invention are illustrated in the following representative examples, which are intended to be illustrative and non-limiting. EXAMPLES:

[0108] Example 1: Process for the preparation of 2-bromo-benzo trifluoride with nitrosyl sulfuric acid (NS A) without catalyst

[0109] Charge nitrosyl sulfuric acid (NSA) (293 gm) into round bottom flask at 25-30°C, cool the reaction to 15-25°C, add 2-amino benzotrifluoride (OABTF) (100 gm) slowly and stirred mass for 2-3 hour at 15-25°C. To another round bottom flask charge aqueous hydrogen bromide (157 g) and slowly add water (134 g) under stirring, heat reaction mixture to 50-55°C and add above diazonium salt dropwise at 50-55°C by using a dropping funnel. Maintain the reaction mass at 50-55°C for 1 hour. Monitor reaction progress by gas chromatography (GC), after completion cool reaction mixture to room temperature, add water, stir, separate organic and aqueous layer. Again, extract aqueous layer with methylene dichloride, combine organic layers, wash with sodium hydroxide solution and again wash organic layers with hydrochloric acid (HC1) solution. Concentrate organic layer on rotavapor to get crude product, which was purified by column distillation. Crude weight= 131 g, Yield= 97%, Purity= 98%.

[0110] Impurities: Impurity- l(Des-Bromo): Nil; Impurity-2(Dibromo): 0.17% (by GC).

[0111] Example 2: Process for the preparation of 2,4,5-trifluoro-bromo benzene with nitrosyl sulfuric acid (NSA) without catalyst

[0112] Charge nitrosyl sulfuric acid (NSA) (320 gm) into round bottom flask at 25-30°C, cool the reaction to 15-25°C, add 2,4,5-trifluoroaniline (100 gm) slowly and stirred mass for 2-3 hour at 15-25°C. To another round bottom flask charge aqueous hydrogen bromide (172 gm) and slowly add water (146.38 gm) under stirring, heat reaction mass to 50-55°C and add above diazonium salt dropwise at 50-55°C by using a dropping funnel. Maintain reaction mass at 50-55°C for 1 hour. Monitor reaction progress by gas chromatography (GC), after completion cool reaction mass to room temperature, add water, stir, separate organic and aqueous layers. Extract again aqueous layer with methylene dichloride, combine organic layers, wash with sodium hydroxide solution and again wash organic layer wash with hydrochloric acid (HC1) solution. Concentrate organic layer on rotavapor to get crude product, which was purified by column distillation. Yield= 97%, Crude Purity= 98%.

[0113] Impurities: Impurity- l(Des-Bromo): 0.01%, Impurity-2(Dibromo): 0.15% (by GC).

[0114] Example 3: Process for the preparation of 2,4,5-trifluoro-chloro benzene with nitrosyl sulfuric acid (NS A) without catalyst

[0115] Charge nitrosyl sulfuric acid (NSA) (320 gm) into round bottom flask at 25-30°C, cool the reaction to 15-25°C, add 2,4,5-Trifluoroaniline (100 gm) slowly and stirred mass for 2-3 hours at 15-25°C. To another round bottom flask charge aqueous hydrogen chloride (80.75 g) and slowly add water (146.38 gm) under stirring, heat reaction mass to 50-55°C and add above diazonium salt dropwise at 50-55°C by using dropping funnel. Maintain reaction mass at 50-55°C for 1 hour. Monitor reaction progress by gas chromatography (GC), after completion cool reaction mass to room temperature, add water, stir, separate organic and aqueous layer. Extract again aqueous layer with methylene dichloride, combine organic layers, wash with sodium hydroxide solution and again wash organic layer with hydrochloric acid (HC1) solution. Concentrate organic layer on rotavapor to get crude product, which was purified by column distillation. Yield= 95%, Crude Purity=97%.

[0116] Impurities: Impurity- l(Des-Chloro): 0.02%, Impurity-2(Dichloro): 0.11% (by GC).

[0117] Example 4: Process for the preparation of 1,2, 4, 5 -tetrafluorobenzene with nitrosyl sulfuric acid (NSA) without catalyst

[0118] Charge nitrosyl sulfuric acid (NSA) (320 gm) into round bottom flask at 25-30°C, cool the reaction to 15-25°C, add 2,4,5-trifluoroaniline (100 gm) slowly and stirred mass for 2-3 hours at 15-25°C. To another round bottom flask charge aqueous fluoroboric acid (71.63 g) and slowly add water (146.38 gm) under stirring, heat reaction mass to 50-55°C and add above diazonium salt dropwise at 50-55°C by using dropping funnel. Maintain reaction mass at 50-55°C for 1 hour. Monitor reaction progress by gas chromatography (GC), after completion cool reaction mass to room temperature, add water, stir, separate organic and aqueous layer. Extract again aqueous layer with methylene dichloride, combine organic layers, wash with sodium hydroxide solution and again wash organic layer wash with hydrochloric acid (HC1) solution. Concentrate organic layer on rotavapor to get crude product, which was purified by column distillation. Yield= 95%, Crude Purity= 96%.

[0119] Impurity: Impurity-1(2, 4, 5-Trifluoro benzene): Nil. (by GC).

[0120] Example 5: Process for the preparation of 2-bromo-benzo trifluoride with sodium nitrite (NaNO2) without catalyst (Comparative example having low yield as compare to using NS A)

[0121] 2-aminobenzotrifluoride (100.0 g) is added to the aqueous hydrogen bromide (420.0 g) at room temperature, then cool reaction mixture to -5 to 0°C and dropwise add sodium nitrite solution (129 g) at -5 to 0°C. To another round bottom flask charge hydrogen bromide (166.64 g), heat reaction mixture to 95-100°C (reflux) and add above diazonium salt dropwise at 95-100°C by using a dropping funnel. Maintain reaction mass at 95-100°C for 3 to 4 hours. Reaction progress monitor by gas chromatography (GC), after completion cool reaction mixture to room temperature and extract with methylene dichloride, wash with sodium hydroxide solution and wash with water. Concentrate organic layer on rotavapor to get crude product, which was purified by column distillation. Crude Yield= 66%, Purity=97%.

[0122] Impurities: Impurity- l(Des-Bromo): 0.11%, Impurity-2(Dibromo): 0.45% (by GC).

[0123] Comparative Example 1: Process for the preparation of 2-bromo-benzo trifluoride with nitrosyl sulfuric acid (NSA) with catalyst Charge nitrosyl sulfuric acid (NSA) (293 gm,) into round bottom flask at 25-30°C, cool the reaction to 15-25°C, add copper(I) bromide and 2-amino benzotrifluoride (OABTF) (100 gm) slowly and stir mass for 2-3 hours at 15-25°C. To another round bottom flask charge aqueous hydrogen bromide (157 g) and slowly add water (134 g) under stirring, heat reaction mass to 50-55°C and add above diazonium salt dropwise at 50-55°C by using dropping funnel. Maintain the reaction mass at 50- 55°C for 1 hour. Monitor reaction progress by gas chromatography (GC), after completion cool reaction mass to room temperature, add water, stir, separate organic and aqueous layer. Again, extract aqueous layer with methylene dichloride, combine organic layers, wash with sodium hydroxide solution and wash again organic layer wash with hydrochloric acid (HC1) solution. Concentrate organic layer on rotavapor to get crude product, which was purified by column distillation. Crude Weight= 131 gram, Yield= 97%, Purity =98%.

[0124] Impurities: Impurity-1 (Des-Bromo): 0.24%; Impurity-2(Dibromo): 0.72%.

[0125] Comparative Example 2: Process for the preparation of 2,4,5 -trifluoro bromo benzene with nitrosyl sulfuric acid (NSA) with catalyst

[0126] Charge nitrosyl sulfuric acid (NSA) (320 gm,) and copper(I) bromide (17.8 g) into round bottom flask at 25-30°C, cool the reaction to 15-25°C, add 2,4,5- trifluoroaniline (100 gm) slowly and stir mass for 2-3 hour at 15-25°C. To another round bottom flask charge aqueous hydrogen bromide (172 gm) and slowly add water (146.38 gm) under stirring, heat reaction mass to 50-55°C and add above diazonium salt dropwise at 50-55°C by using a dropping funnel. Maintain reaction mass at 50-55°C for 1 hour. Monitor reaction progress by gas chromatography (GC), after completion cool reaction mass to room temperature, add water, stir, separate organic and aqueous layers. Extract again aqueous layer with methylene dichloride, combine organic layers, wash with sodium hydroxide solution and again organic layer wash with hydrochloric acid (HC1) solution. Concentrate organic layer on rotavapor to get crude product, which was purified by column distillation. Yield= 93%, Crude Purity=98%. Impurities: Impurity- l(Des-Bromo): 0.21%, Impurity-2(Dibromo): 0.65% (by GC).

[0127] Comparative Example 3: Process for the preparation of 2,4,5 -trifluoro chloro benzene with nitrosyl sulfuric acid (NSA) with catalyst

[0128] Charge nitrosyl sulfuric acid (NSA) (320 gm) and copper(I) bromide (17.8 g,) into round bottom flask at 25-30°C, cool the reaction to 15-25°C, add 2,4,5- trifluoroaniline (100 gm) slowly and stir mass for 2-3 hours at 15-25°C. To another round bottom flask charge aqueous hydrogen chloride (80.75 g) and slowly add water (146.38 gm) under stirring, heat reaction mass to 50-55°C and add above diazonium salt dropwise at 50-55°C by using dropping funnel. Maintain reaction mass at 50-55°C for 1 hour. Monitor reaction progress by gas chromatography (GC), after completion cool reaction mass to room temperature, add water, stir, separate organic and aqueous layer. Extract again aqueous layer with methylene dichloride, combine organic layers, wash with sodium hydroxide solution and again wash organic layer with hydrochloric acid (HC1) solution. Concentrate organic layer on rotavapor to get crude product, which was purified by column distillation. Yield= 91%, Crude Purity=97%.

[0129] Impurities: Impurity- l(Des-Chloro): 0.19%, Impurity-2(Dichloro): 0.69% (by GC).

[0130] Comparative Example 4: Process for the preparation of 1, 2,4,5 - tetrafluorobenzene with nitrosyl sulfuric acid (NSA) with catalyst

[0131] Charge nitrosyl sulfuric acid (NSA) (320 gm,) and copper(I) bromide (17.8 g,) into round bottom flask at 25-30°C, cool the reaction to 15-25°C, add 2,4,5- trifluoroaniline (100 gm) slowly and stirred mass for 2-3 hours at 15-25°C. To another round bottom flask charge aqueous fluoroboric acid (71.63 g) and slowly add water (146.38 gm) under stirring, heat reaction mass to 50-55°C and add above diazonium salt dropwise at 50-55°C by using dropping funnel. Maintain reaction mass at 50-55°C for 1 hour. Monitor reaction progress by gas chromatography (GC), after completion cool reaction mass to room temperature, add water, stir, separate organic and aqueous layer. Extract again aqueous layer with methylene dichloride, combine organic layers, wash with sodium hydroxide solution and again organic layer wash with hydrochloric acid (HC1) solution. Concentrate organic layer on rotavapor to get crude product, which was purified by column distillation. Yield= 91%, Crude Purity= 96%.

[0132] Impurity: Impurity-1 (2,4,5-Trifluoro benzene): 0.39% (by GC).

[0133] Comparative Example 5: Process for the preparation of 2-bromo-benzo trifluoride with sodium nitrite (NaNCh) with catalyst (Comparative example having low yield as compare to using NS A)

[0134] 2-aminobenzotrifluoride (100.0 g) is added to the aqueous hydrogen bromide (420.0 g) at room temperature, then cool reaction mixture to -5 to 0°C and added dropwise sodium nitrite solution (129 g) at -5 to 0°C. To another round bottom flask charge hydrogen bromide (166.64 g) and copper (I) bromide (17.8 g), heat reaction mixture to 95-100°C (reflux) and add above diazonium salt dropwise at 95-100°C by using dropping funnel. Maintain reaction mass at 95-100°C for 3 to 4 hours. Reaction progress was monitored by gas chromatography (GC), after completion, cool the reaction mixture to room temperature and extract with methylene dichloride, wash with sodium hydroxide solution and water. Concentrate organic layer on rotavapor to get crude product, which was purified by column distillation. Crude Yield= 56%, Purity=97%.

[0135] Impurities: Impurity- l(Des-Bromo): 0.55%, Impurity-2(Dibromo): 1.5% (by GC).

[0136] General procedure for the examples which follow:

[0137] Preparation of substituted aryl halide compound of Formula (I) without using catalyst.

[0138] Charge nitrosyl sulfuric acid (NSA) (293 gm) into round bottom flask at 25-30°C, cool the reaction to 15-25°C, add substituted aryl amine compound of Formula (II) (100 gm) slowly and stir mass for 2-3 hour at 15-25°C. To another round bottom flask charge aqueous halogenation reagent (157 g) and slowly add water (134 g) under stirring, heat reaction mixture to 50-55°C and add above diazonium salt dropwise at 50-55°C by using a dropping funnel. Maintain the reaction mass at 50-

[0139] 5 55 °C for 1 hour. Monitor reaction progress by gas chromatography (GC), after completion cool reaction mixture to room temperature, add water, stir, separate organic and aqueous layer. Again, extract aqueous layer with methylene dichloride, combine organic layers, wash with sodium hydroxide solution and again wash organic layers with hydrochloric acid (HC1) solution. Concentrate organic layer on 10 rotavapor to get crude product, which was purified by column distillation. The crude substituted aryl halide compound of Formula (I) thus obtained was purified by distillation.

[0140] The following table 1 depicts the further examples for the preparation of substituted aryl halide compound of Formula (I) from substituted aryl amine compound of 15 Formula (II) with different halogenation reagents with and without the use of catalyst, which are prepared by using the process of the present invention.

[0141] Table: 1

[0142]

[0143] The embodiments herein and the various features and advantageous details thereof are explained with reference to the non-limiting embodiments in the description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein. The description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and / or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.

[0144] While considerable emphasis has been placed herein on the particular features of this invention, it will be appreciated that various modifications can be made, and that many changes can be made in the preferred embodiments without departing from the principles of the invention. These and other modifications in the nature of the invention or the preferred embodiments will be apparent to those skilled in the art from the invention 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.

[0145] Various features and embodiments of the present invention are illustrated in the following representative examples, which are intended to be illustrative and non-limiting.

[0146] 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.

[0147] 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

CLAIMS1. A process for the preparation of substituted aryl halide compound of Formula (I) from substituted aryl amine compound of Formula (II),X is fluorine, chlorine or bromine;R1is selected from the group consisting of halogen, amino, hydroxy, alkyl, alkenyl, alkoxy, haloalkyl, haloalkoxy, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted cycloalkyl and substituted or unsubstituted cycloalkyloxy; n is 1 to 5; comprising the step of: a. reacting substituted aryl amine compound of Formula (II) with a suitable diazotizing reagent optionally in the presence of suitable acid at a temperature in the range of 5 to 50°C to obtain aryl diazonium salt of substituted aryl amine compound of Formula (II); b. reacting the aryl diazonium salt of substituted aryl amine compound of Formula (II) of step (a) with a suitable halogenating reagent at a temperature in the range of 20 to 120°C, optionally in presence of suitable solvent to obtain substituted aryl halide compound of Formula (I).

2. The process as claimed in claim 1, wherein suitable alkyl, alkenyl, alkoxy, haloalkyl, haloalkoxy, substituted or unsubstituted aryloxy, substituted orunsubstituted cycloalkyl, substituted or unsubstituted cycloalkyloxy are selected from the group consisting of methyl, ethyl, propyl, 1 -methylethyl, butyl, 1 -methylpropyl, 2-methylpropyl, 1,1 -dimethylethyl, pentyl, 1- methylbutyl, 2-methylbutyl, 3 -methylbutyl, 2,2-dimethylpropyl, 1- ethylpropyl, hexyl, 1,1 -dimethylpropyl, 1,2-dimethylpropyl, 1- methylpentyl, 2- methylpentyl, 3 -methylpentyl, 4-methylpentyl, 1,1- dimethylbutyl, 1,2-dimethylbutyl, 1,3- dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3, 3 -dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2- trimethylpropyl, 1,2,2-trimethylpropyl, 1 -ethyl- 1 -methylpropyl and 1- ethyl-2-methylpropyl; ethenyl, 1 -propenyl, 2-propenyl, 1 -methylethenyl, 1- butenyl, 2-butenyl, 3-butenyl, 1 -methyl- 1 -propenyl, 2-methyl-l -propenyl, l-methyl-2 -propenyl, 2- methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3- pentenyl, 4-pentenyl, 1 -methyl- 1-butenyl, 2-methyl-l- butenyl, 3-methyl-l- butenyl, l-methyl-2-butenyl, 2-methyl-2-butenyl, 1,2-propadienyl, 2,4- hexadienyl; methoxy, ethoxy, propoxy, 1 -methylethoxy, butoxy, 1- methylpropoxy, 2 -methylpropoxy, 1,1- dimethylethoxy, pentoxy, 1- methylbutoxy, 2 -methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1- ethylpropoxy; chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1- chloroethyl, 1 -bromoethyl, 1-fluoroethyl, 2- fluoroethyl, 2,2-difluoroethyl,2.2.2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl,2.2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 1,1- dichloro-2,2,2-trifluoroethyl, and l,l,l-trifluoroprop-2-yl; phenyloxy, 4- methylphenoxy, naphthyloxy; cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, and the like.

3. The process as claimed in claim 1 step (a), wherein suitable diazotizing reagents in accordance with the present invention include sodium nitrite,calcium nitrite, potassium nitrite, alkyl nitrite, nitrosyl sulfuric acid or mixture thereof.

4. The process as claimed in claim 1 step (a), wherein suitable acid in accordance with the present invention is selected from mineral acid or organic acid or mixture thereof.

5. The process as claimed in claim 4 wherein suitable mineral acid is selected from the group consisting of hydrochloric acid, sulfuric acid, oleum, or mixture thereof.

6. The process as claimed in claim 4, wherein suitable organic acid is selected from the group consisting of formic acid, acetic acid, trifluoroacetic acid, chlorosulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, or mixture thereof.

7. The process as claimed in claim 1 step (b), wherein suitable halogenating reagent is selected from the group consisting of bromine, hydrogen bromide, iV-bromo- succinimide (NBS), cupric bromide, sodium bromide, potassium bromide, bromine monochloride, hydrogen chloride, iV-chlorosuccinimide, sodium hypochlorite, tert-butyl hypochlorite, hydrofluoric acid, tetrafluoroboric acid (HBF4), hydrogen fluoride, cesium fluoride, potassium fluoride, ammonium fluoride, sodium fluoride, or mixture thereof.

8. The process as claimed in claim 1, wherein suitable solvent in step (b) is selected from the group consisting of monochlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane,dichloroethane, trichloroethane, toluene, diethyl ether, diisopropyl ether, methyl tert- butyl ether, methyl tert- amyl ether, dioxane, tetrahydrofuran, 1, 2-dimethoxy ethane, 1, 2-diethoxy ethane, anisole, acetonitrile, propionitrile, n- or iso-butyronitrile or benzonitrile, N,N- dimethylformamide, A,A-dimethylacetamide, A-methyl formanilide, N- methylpyrrolidone, hexamethylphosphoric triamide, dimethyl sulfoxide, sulfolane, methanol, ethanol, isopropanol, polyethylene glycols, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl benzoate, ethyl benzoate, butyl benzoate, acetone, acetic acid, water, or mixtures thereof.

9. The process as claimed in claim 1 step (a), wherein the molar ratio of substituted aryl amine compound of Formula (II) and a suitable diazotizing reagent is in the range of 1:0.5 to 1:1.5.

10. The process as claimed in claim 1 step (b), wherein the molar ratio of substituted aryl amine compound of Formula (II) and a suitable halogenating reagent is in the range of 1: 1 to 1:2.

11. The process as claimed in claim 1, wherein the yield of the substituted aryl halide compound of Formula (I) is more than 95%.

12. The process as claimed in claim 1, wherein, the des-halo impurity is less than 0.02% and di-halo impurity is less than 0.2% in the substituted aryl halide compound of Formula (I).

13. A process for the preparation of substituted aryl halide compound of Formula (I) from substituted aryl amine compound of Formula (II)Formula (II) Formula (I) wherein,X is fluorine, chlorine or bromine;R1is selected from the group consisting of halogen or amino n is 1 to 5; comprising the step of: a. reacting substituted aryl amine compound of Formula (II) with a suitable diazotizing reagent optionally in the presence of suitable acid at a temperature in the range of 5 to 50°C to obtain aryl diazonium salt of substituted aryl amine compound of Formula (ID; b. reacting the aryl diazonium salt of substituted aryl amine compound of Formula (II) of step (a) with a suitable halogenating reagent at a temperature in the range of 20 to 120°C, optionally in presence of suitable solvent to obtain substituted aryl halide compound of Formula (I).

14. The process as claimed in claim 13 step (a), wherein said suitable diazotizing reagents in accordance with the present invention include sodium nitrite, calcium nitrite, potassium nitrite, alkyl nitrite, nitrosyl sulfuric acid or mixture thereof.

15. The process as claimed in claim 13 step (a), wherein said suitable acid in accordance with the present invention is selected from mineral acid or organic acid or mixture thereof.

16. The suitable mineral acid as claimed in claim 15 is selected from the group consisting of hydrochloric acid, sulfuric acid, oleum, or mixture thereof.

17. The suitable organic acid as claimed in claim 15, is selected from the group consisting of formic acid, acetic acid, trifluoroacetic acid, chlorosulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, or mixture thereof.

18. The process as claimed in claim 13 step (b), wherein said suitable halogenating reagent is selected from the group consisting of bromine, hydrogen bromide, iV-bromo- succinimide (NBS), cupric bromide, sodium bromide, potassium bromide, bromine monochloride, hydrogen chloride, A-chlorosuccinimide, sodium hypochlorite, tert-butyl hypochlorite, hydrofluoric acid, tetrafluoroboric acid (HBF4), hydrogen fluoride, cesium fluoride, potassium fluoride, ammonium fluoride, sodium fluoride, or mixture thereof.

19. The process as claimed in claim 13, wherein suitable solvent in step (b) is selected from the group consisting of monochlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane, trichloroethane, toluene, diethyl ether, diisopropyl ether, methyl tert- butyl ether, methyl tert- amyl ether, dioxane, tetrahydrofuran, 1, 2-dimethoxy ethane, 1, 2-diethoxy ethane, anisole, acetonitrile, propionitrile, n- or iso-butyronitrile or benzonitrile, N,N- dimethylformamide, iV-dimethylacetamide, iV-methyl formanilide, N- methylpyrrolidone, hexamethylphosphoric triamide, dimethyl sulfoxide, sulfolane, methanol, ethanol, isopropanol, polyethylene glycols, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl benzoate, ethyl benzoate, butyl benzoate, acetone, acetic acid, water, or mixtures thereof.

20. The process as claimed in claim 13 step (a), wherein the molar ratio of substituted aryl amine compound of Formula (II) and a suitable diazotizing reagent is in the range of 1:0.5 to 1:1.

5.

21. The process as claimed in claim 13 step (b), wherein the molar ratio of substituted aryl amine compound of Formula (II) and a suitable halogenating reagent is in the range of 1: 1 to 1:2.

22. The process as claimed in claim 13, wherein the yield of the substituted aryl halide compound of Formula (I) is more than 95%.

23. The process as claimed in claim 13, wherein, the des-halo impurity is less than 0.02% and di-halo impurity is less than 0.2% in the substituted aryl halide compound of Formula (I).

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