DESC:
Field of the invention
The present invention relates to a process for preparation of aminobiphenyl compounds and intermediates thereof. More particularly, the present invention relates to a process for preparation of aminobiphenyl compounds and use of said aminobiphenyl compounds in preparation of agrochemical or pharmaceutically active ingredients.
Background of invention
For many decades, biphenyl compounds have been considered as fundamental backbone in synthetic organic chemistry and natural products due to their presence in agrochemical active ingredients, pharmaceutical active ingredients and natural products.
Agrochemically active fungicides such Bixafen, Fluxapyroxad and Pyraziflumid having aminobiphenyl backbone are highly efficacious and are in high demand. All these fungicides listed above are succinate dehydrogenase inhibitors (SDHI) which have exhibited a prominent role in controlling turfgrass diseases and provides an alternative to fungicides in other mode-of-action groups for resistance management.
Bixafen, having chemical name N-(3',4'-Dichloro-5-fluorobiphenyl-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide was first disclosed in US7329633. Fluxapyroxad, having chemical name 3-(Difluoromethyl)-1-methyl-N-(3',4',5'-trifluorobiphenyl-2-yl)-1H-pyrazole-4-carboxamide was first disclosed in US8008232.
A continuous effort is being made to develop economical as well as greener processes for preparation of these fungicides. Most of the processes for preparation of active ingredients such Bixafen, Fluxapyroxad and Pyraziflumid proceeds through aminobiphenyl compounds of formula (I)

wherein, X1 and X2 are independently selected from hydrogen, bromine, chlorine, iodine or fluorine; Y is selected from hydrogen or a protecting group; n is 0, 1, 2 or 3; and m is 0, 1 or 2.
Aminobiphenyl compounds are important intermediate which are widely used in a plurality of fields such as medicine, agricultural chemicals and chemical industry. Generally, aminobiphenyl compounds are prepared by reacting phenylboronic acids with phenyl halides through a Suzuki-Miyaura coupling wherein palladium-based catalyst are used. Most of the methods known in prior art involves use of a homogeneous catalyst system, in general composed of the noble metal such as palladium and ligands which are in a particular stoichiometric ratio with respect to one another. These noble metals in the catalysts are precious metal and expensive, hence their recovery is important after completion of reaction. However, the recovery/separation of these noble catalyst is very difficult and cumbersome. Furthermore, the ligands used in the process are discarded in the environment to some extent which makes such processes environmentally unfriendly.
It is known that Suzuki-Miyaura coupling can also be carried out by using heterogeneous catalysts. Chemistry - An Asian Journal (2010), 5(11), 2336-2340 discloses a process for preparation of an aminobiphenyl compound by reacting 2-bromoaniline with 4-chlorophenylboronic acid in presence of Pd/C and potassium carbonate at 95°C in mixture of water and dioxane. However, the yield of the aminobiphenyl compound obtained is as low as 68%, which makes process uneconomical for large scale production.

The inventors of present invention have developed an alternative process for preparation of aminobiphenyl compounds using palladium catalysts wherein the catalyst is efficiently recovered without adversely affecting its activity and the process also provides aminobiphenyl compounds in high yield and purity.

Objective of the invention
It is an objective of the present invention to provide aminobiphenyl compounds of formula (I) in high yield and purity.
It is an objective of the present invention to provide a process for the preparation of aminobiphenyl compounds of formula (I).
It is another objective of the present invention to provide a process for the preparation of aminobiphenyl compounds of formula (I) using palladium catalyst, wherein the catalyst used is easily recoverable, substantially non-contaminated after the reaction and can be reused.
It is an objective of the present invention to provide an economic and eco-friendly process for the preparation of aminobiphenyl compounds of formula (I).
Summary of the invention
In an aspect of the present invention, there is provided a process for preparation of aminobiphenyl of formula (I) or salts thereof,

wherein, X1 and X2 are independently selected from hydrogen, bromine, chlorine, iodine or fluorine; Y is a selected from hydrogen, a protecting group or a substituted pyrazole carbonyl group; n is 0, 1, 2 or 3; and m is 0, 1 or 2; provided when X1 is chlorine, n is 2 or 3;
comprising a step of reacting an organoboron compound of formula (II)

selected from the group comprising of
a) organoboron compound of formula (II) wherein p is 2; q is 1; each Z is hydroxy group; X1 and n are same as defined above; or anhydride, dimer or trimer thereof
b) organoboron compound of formula (II) wherein p is 2; q is 1; each Z is independently selected from the group consisting of bromine, chlorine, iodine, fluorine, C1-C4 alkyl-, C6-C10 aryl, C1-C4 alkoxy and C6-C10 aryloxy-residues; X1 and n are same as defined above;
c) organoboron compound of formula (II) wherein p is 1; q is 2; Z is selected from the group consisting of hydroxy, bromine, chlorine, iodine, fluorine, C1-C4 alkyl-, C6-C10 aryl, C1-C4 alkoxy and C6-C10 aryloxy-residues; X1 and n are same as defined above;
d) an organoboron compound of formula (II) wherein p is 2; q is 1; Z is selected from C1-C4-alkoxy residues which together with the boron atom they are attached form a 5- or 6-membered ring which may be substituted by C1-C4-alkyl-residues; X1 and n are same as defined above;
e) an organoboron compound of formula (II) wherein p is 3; q is 1; Z is selected from the group consisting of hydroxy group, bromine, chlorine, iodine, fluorine, C1-C4 alkyl-, C6-C10 aryl, C1-C4 alkoxy and C6-C10 aryloxy-residues,
and wherein the negative charge of the boronate anion is compensated by a cation; X1 and n are same as defined above;
f) an organoboron compound of formula (II) wherein p is 0; q is 3; X1 and n are same as defined above
g) an organoboron compound of formula (II) wherein p is 0; q is 4; X1 and n are same as defined above
h) an organoboron compound of formula (II) wherein p is 0; q is 4; X1 and n are same as defined above and wherein the negative charge of the boronate anion is compensated by a cation;
with a compound of formula (III)

wherein Y, X2 and m are same as defined above;
in presence of a supported palladium catalyst to obtain a compound of formula (I).
In another aspect of the present invention, the compound of formula (I) prepared according to above process is used as an intermediate for preparation of Bixafen.
In another aspect of the present invention, the compound of formula (I) prepared according to above process is used as an intermediate for preparation of Fluxapyroxad.
Detailed Description of the invention
The following description is provided to assist in a comprehensive understanding of exemplary embodiments of the disclosure. It includes various specific details to assist in that understanding but these are to be regarded as merely exemplary. Accordingly, those of ordinary skill in the art will recognize that various changes and modifications of the embodiments described herein can be made without departing from the scope of the disclosure. In addition, descriptions of well-known functions and constructions are omitted for clarity and conciseness. The terms used in the following description are not limited to the bibliographical meanings but are merely used by the inventor to enable a clear and consistent understanding of the disclosure. Accordingly, it should be apparent to those skilled in the art that the following description of exemplary embodiments of the present disclosure are provided for illustration purpose only and not for limiting the scope of the disclosure as defined by the appended claims and their equivalents.

For the purposes of the present disclosure, it is to be understood that the disclosure may assume various alternative variations and step sequences, except where expressly specified to the contrary. Moreover, other than in any operating examples, or where otherwise indicated, all numbers expressing, for example, quantities of materials/ingredients used in the specification are to be understood as being modified in all instances by the term “about”. Thus, before describing the present disclosure in detail, it is to be understood that this disclosure is not limited to particularly exemplified systems or process parameters that may of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the disclosure only and is not intended to limit the scope of the disclosure in any manner. The use of examples anywhere in this specification including examples of any terms discussed herein is illustrative only, and in no way limits the scope and meaning of the disclosure or of any exemplified term. Prior to setting forth the present subject matter in detail, it may be helpful to provide definitions of certain terms used herein.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the disclosure, suitable methods and materials are described herein.

As used herein, the terms “comprising”, “including”, “having”, “containing”, “involving” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. The terms “preferred” and “preferably” refer to embodiments of the disclosure that may afford certain benefits, under certain circumstances. The aspects and embodiments described herein shall also be interpreted to replace the clause “comprising” with either “consisting of” or with “consisting essentially of” or with “consisting substantially of”.

“About” or “approximately” as used herein is inclusive of the stated value and means within an acceptable range of deviation for the particular value as determined by one of ordinary skill in the art, considering the measurement in question and the error associated with measurement of the particular quantity (i.e., the limitations of the measurement system). For example, “about” can mean within one or more standard deviations, or within ±10% or ±5% of the stated value.

The use of the terms “a”, “an” and “the” and similar referents (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms first, second etc., as used herein are not meant to denote any particular ordering, but simply for convenience to denote a plurality of, for example, layers.

All methods described herein can be performed in a suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”), is intended merely to better illustrate the disclosure and does not pose a limitation on the scope of the disclosure unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the disclosure as used herein.

While the disclosure has been described with reference to an exemplary embodiment, it will be understood by those skilled in the art that various changes may be made, and equivalents may be substituted for elements thereof without departing from the scope of the disclosure. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the disclosure without departing from the essential scope thereof. Therefore, it is intended that the disclosure is not limited to the particular embodiment disclosed as the best mode contemplated for carrying out this disclosure, but that the disclosure will include all embodiments falling within the scope of the appended claims.
As used herein, the term “acyl” refers to the group RaC(O)-, where Ra is C1 to C6 alkyl group.
As used herein the (C1-C6) alkyl means a linear or branched chain alkyl having 1 to 6 carbon atoms. Examples of (C1-C6) alkyls include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl and the like.
The term “aminobiphenyl of formula (I)” is used interchangeably with the term “aminobiphenyl of formula (I) or salts thereof”
The term “compound of formula (Ia)” is used interchangeably with the term “compound of formula (Ia) or salts thereof”
The term “compound of formula (Ib)” is used interchangeably with the term “compound l of formula (Ib) or salts thereof”
A salt can form from a compound in any manner familiar to the skilled artisan. Accordingly, the recitation "to form a compound or salt thereof includes embodiments where a compound is formed and the salt is subsequently formed from the compound in a manner familiar to the skilled artisan.
In an aspect of the present invention, there is provided a process for preparation of aminobiphenyl of formula (I) or salts thereof,

wherein, X1 and X2 are independently selected from hydrogen, bromine, chlorine, iodine or fluorine; Y is a selected from hydrogen, a protecting group or a substituted pyrazole carbonyl group; n is 0, 1, 2 or 3; and m is 0, 1 or 2; provided that when X1 is chlorine, n is 2 or 3;
comprising step of reacting an organoboron compound of formula (II)

selected from the group comprising of
a) organoboron compound of formula (II) wherein p is 2; q is 1; each Z is hydroxy group; X1 and n are same as defined above; or anhydride, dimer or trimer thereof
b) organoboron compound of formula (II) wherein p is 2; q is 1; each Z is independently selected from the group consisting of F, Cl, Br, I, C1-C4 alkyl-, C6-C10 aryl, C1-C4 alkoxy and C6-C10 aryloxy-residues; X1 and n are same as defined above;
c) organoboron compound of formula (II) wherein p is 1; q is 2; Z is selected from the group consisting of hydroxy, bromine, chlorine, iodine or fluorine, C1-C4 alkyl-, C6-C10 aryl, C1-C4 alkoxy and C6-C10 aryloxy-residues; X1 and n are same as defined above;
d) an organoboron compound of formula (II) wherein p is 2; q is 1; Z is selected from C1-C4-alkoxy residues which together with the boron atom they are attached form a 5- or 6-membered ring which may be substituted by C1-C4-alkyl-residues; X1 and n are same as defined above;
e) an organoboron compound of formula (II) wherein p is 3; q is 1; Z is selected from the group consisting of hydroxy group, bromine, chlorine, iodine or fluorine C1-C4 alkyl-, C6-C10 aryl, C1-C4 alkoxy and C6-C10 aryloxy-residues,
and wherein the negative charge of the boronate anion is compensated by a cation; X1 and n are same as defined above;
f) an organoboron compound of formula (II) wherein p is 0; q is 3; X1 and n are same as defined above
g) an organoboron compound of formula (II) wherein p is 0; q is 4; X1 and n are same as defined above
h) an organoboron compound of formula (II) wherein p is 0; q is 4; X1 and n are same as defined above and wherein the negative charge of the boronate anion is compensated by a cation;
with a compound of formula (III)

wherein Y, X2 and m are same as defined above;
in presence of a supported palladium catalyst to obtain a compound of formula (I).
In an embodiment, there is provided a process for preparation of aminobiphenyl of formula (I) or salts thereof,

wherein, X1 and X2 are independently selected from hydrogen, bromine, chlorine, iodine or fluorine; Y is a selected from hydrogen, a protecting group or a substituted pyrazole carbonyl group; n is 0, 1, 2 or 3; and m is 0, 1 or 2; provided that when X1 is chlorine, n is 2 or 3;
comprising step of reacting an organoboron compound of formula (II)

wherein p is 2; q is 1; each Z is hydroxy group; X1 and n are same as defined above; or anhydride, dimer or trimer thereof;
with a compound of formula (III)

wherein Y, X2 and m are same as defined above;
in presence of a supported palladium catalyst to obtain a compound of formula (I).

In an embodiment, the organoboron compound of formula (II) wherein p is 2; q is 1; each Z is hydroxy group; X1 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; n is 0, 1, 2 or 3; provided that when X1 is chlorine, n is 2 or 3; or anhydride, dimer or trimer thereof.
In an embodiment, the organoboron compound of formula (II) wherein p is 2; q is 1; each Z is hydroxy group; X1 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; n is 0, 1, 2 or 3; provided that when X1 is chlorine, n is 2 or 3.
In an embodiment, the boronic acid compound of formula (II) is selected from compound of formula (IIa) or (IIb).

In an embodiment the compound of formula (IIa) is 3,4-dichlorophenylboronic acid.
In an embodiment the compound of formula (IIb) is (3,4,5-trifluorophenyl)boronic acid.
The compound of formula (II) used as starting materials in said process of present invention are prepared by methods known in the art.
In an embodiment, the organoboron compound of formula (II) is wherein p is 2; q is 1; each Z is independently selected from the group consisting of bromine, chlorine, iodine or fluorine, C1-C4 alkyl-, C6-C10 aryl, C1-C4 alkoxy and C6-C10 aryloxy-residues.
X1 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; n is 0, 1, 2 or 3; provided that when X1 is chlorine, n is 2 or 3.
In an embodiment, the organoboron compound of formula (II) is wherein p is 1; q is 2; Z is selected from the group consisting of hydroxy, F, Cl, Br, I, C1-C4 alkyl-, C6-C10 aryl, C1-C4 alkoxy and C6-C10 aryloxy-residues; X1 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; n is 0, 1, 2 or 3; provided that when X1 is chlorine, n is 2 or 3.
In an embodiment, the organoboron compound of formula (II) is wherein p is 2; q is 1; Z is selected from C1-C4-alkoxy residues which together with the boron atom they are attached form a 5- or 6-membered ring which may be substituted by C1-C4-alkyl-residues; X1 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; n is 0, 1, 2 or 3; provided that when X1 is chlorine, n is 2 or 3.
In an embodiment, the organoboron compound of formula (II) is wherein p is 3; q is 1; Z is selected from the group consisting of hydroxy group, F, Cl, Br, I, C1-C4 alkyl-, C6-C10 aryl, C1-C4 alkoxy and C6-C10 aryloxy-residues,
and wherein the negative charge of the boronate anion is compensated by a cation; X1 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; n is 0, 1, 2 or 3; provided that when X1 is chlorine, n is 2 or 3.
In an embodiment, the organoboron compound of formula (II) is wherein p is 0; q is 3; X1 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; n is 0, 1, 2 or 3; provided that when X1 is chlorine, n is 2 or 3;
In an embodiment, the organoboron compound of formula (II) is wherein p is 0; q is 4; X1 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; n is 0, 1, 2 or 3; provided that when X1 is chlorine, n is 2 or 3;
In an embodiment, the organoboron compound of formula (II) is wherein p is 0; q is 4; X1 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; n is 0, 1, 2 or 3; provided that when X1 is chlorine, n is 2 or 3; and wherein the negative charge of the boronate anion is compensated by a cation.
In an embodiment, in the compound of formula (III), X2 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; m is 0, 1, 2, 3 or 4 and Y is a selected from hydrogen, a protecting group, or a substituted pyrazole carbonyl group.
In an embodiment, in the compound of formula (III), Y is protecting group selected from group comprising of acyl, tosyl, mesyl, carbamate protecting group such as tert-butyloxycarbonyl, ethylcarbamate, benzyloxycarbonyl, benzene sulfonyl, p-nitrobenzene sulfonyl, trifluoro acetyl, tert-butyl sulfonyl, optionally substituted pyrazole acid, optionally substituted nicotinyl acid and the like.
In an embodiment, in the compound of formula (III), Y is a substituted pyrazole carbonyl group, preferably 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl- group.
In an embodiment, in the compound of formula (III), m is 2, X2 is independently hydrogen, bromine, chlorine, iodine or fluorine; and Y is protecting group or substituted pyrazole carbonyl group. In an embodiment, the compound of formula (III) is compound of formula (IIIa); wherein m is 2, X2 is independently bromine and fluorine; Y is protecting group or substituted pyrazole carbonyl group.

In an embodiment, in the compound of formula (IIIa), X2 is independently selected from hydrogen, bromine, or fluorine; m is 0, 1 or 2; and Y is acetyl group.
In an embodiment, in the compound of formula (IIIa) is 2-bromo, 4-fluoro acetanilide.
In an embodiment, in the compound of formula (IIIa), X2 is independently selected from hydrogen, bromine, or fluorine; m is 0, 1 or 2; and Y is 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl group.
In an embodiment, in the compound of formula (IIIa) is N-(2-bromo-4-fluorophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide.
In an embodiment, in the compound of formula (III), wherein m is 1; X2 is bromine; and Y is protecting group or a substituted pyrazole carbonyl group.
In an embodiment, in the compound of formula (III), wherein m is 1; X2 is hydrogen, bromine, chlorine, iodine or fluorine; and Y is protecting group or a substituted pyrazole carbonyl group.
In an embodiment, the compound of formula (III) is compound of formula (IIIb); wherein m is 1; X2 is bromine; and Y is protecting group or a substituted pyrazole carbonyl group.

In an embodiment, in the compound of formula (IIIb), X2 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; m is 0, 1 or 2; and Y is acetyl group.
In an embodiment, in the compound of formula (IIIb) is 2-bromo acetanilide.
In an embodiment, in the compound of formula (IIIb), X2 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; m is 0, 1 or 2; and Y is 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl group.
In an embodiment, in the compound of formula (IIIb) is N-(2-bromophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide.
In an embodiment, the compound of formula (III) is selected from 2-bromo, 4-fluoro acetanilide, 2-bromo acetanilide, N-(2-bromo-4-fluorophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide or N-(2-bromophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide.
The compound of formula (III) used as starting materials in said process of present invention are prepared by methods known in the art.
In an embodiment, the amount compound of formula (III) used may vary from 0.5 to 1.5 moles with respect to compound of formula (II).
In an embodiment, the amount compound of formula (III) used may vary from 0.8 to 1.2 moles with respect to compound of formula (II).
In an embodiment, supported palladium catalyst used is selected from metallic palladium, organic or inorganic palladium compounds.
Suitable organic or inorganic palladium compounds are preferably compounds such as palladium acetate, palladium hydroxide, palladium propionate, or palladium salts such as palladium chloride, palladium hydroxide, palladium bromide, palladium iodide, palladium nitrate or palladium sulfate.
In an embodiment, the palladium catalyst used is supported on inert material such as activated carbon, aluminum oxide, barium sulfate, calcium carbonate, pumice, alumina, kieselguhr or silica gel.
In an embodiment, the palladium catalyst is selected from, but not limited to palladium black or palladium on supports, such as palladium on carbon, palladium hydroxide on carbon, palladium on barium sulfate, palladium on calcium carbonate.
In an embodiment, the palladium catalyst is selected from palladium on carbon, palladium hydroxide on carbon, palladium on barium sulfate or palladium on calcium carbonate.
In an embodiment, the supported palladium catalyst is palladium on carbon.
In an embodiment, the supported palladium catalyst contains from about 1% to about 30% by weight of palladium, based on the support material.
In an embodiment, the supported palladium catalyst contains from about 2% to about 20% by weight of palladium, based on the support material.
In an embodiment, the supported palladium catalyst contains from about 2% to about 15% by weight of palladium, based on the support material.
In an embodiment, the heterogenous palladium catalyst is used in an amount ranging from about 0.01 mol% to about 10 mol%.
In an embodiment, said reaction of the organoboron compound of formula (II) with a compound of formula (III) is carried out in presence of a solvent selected from, but not limited to, water, ether, hydrocarbon, alcohol, ketone, amide or mixture thereof.
In an embodiment, the solvent used is selected from, but not limited to, water, ethers such as dimethoxyethane, diethylene glycol dimethyl ether, tetrahydrofuran, dioxane and tert-butyl methyl ether; hydrocarbons such as n-hexane, n-heptane, cyclohexane, benzene, toluene and xylene; alcohols such as methanol, ethanol, 1-propanol, 2-propanol, ethylene glycol, n-butanol, iso-butanol and tert.-butanol; ketones such as acetone, ethyl methyl ketone and isobutyl methyl ketone; amides such as dimethylformamide, dimethylacetamide and N-methylpyrrolidone; or mixtures thereof.
In an embodiment, the solvent used is an alcohol.
In an embodiment, the alcohol used is selected from alcohols like methanol, ethanol, n-propanol, isopropanol, n-butanol, iso-butanol or mixture thereof.
In an embodiment, the alcohol used is n-butanol.
In an embodiment, the process is carried out in presence of a base.
In an embodiment, the base used is selected from group comprising of alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal carbonates, alkali metal bicarbonates, alkali metal and alkaline earth metal acetates, alkali metal and alkaline earth metal formates, alkali metal and alkaline earth metal alkoxides primary, secondary and tertiary amines or mixtures thereof.
In an embodiment, the base used is alkali metal carbonates such as potassium carbonate, sodium carbonate and the likes.
In an embodiment, the amount of base used may vary from about 0.5 to 2 moles with respect to compound of formula (II).
In an embodiment, the amount of base used may vary from about 1 to 1.5 moles with respect to compound of formula (II).
In an embodiment, the process is carried out in presence of a phase transfer catalyst.
In an embodiment, the phase transfer catalyst used is selected from, but not limited to, a quaternary ammonium salt, an amine N-oxide compound, a quaternary phosphonium salt, a crown ether compound and a polyethylene glycol compound. The quaternary ammonium salt is preferable.
In an embodiment, the phase transfer catalyst used is the quaternary ammonium salt such as tetraallyl ammonium hydroxide, tetraallyl ammonium halide.
In an embodiment, the phase transfer catalyst used is the quaternary ammonium salt such as benzyltrialkylmmonium hydroxide, tetrabutylammonium hydroxide, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium chloride, cetyl trimethyl ammonium chloride, dodecyltrimethylammonium chloride, tetrabutyl ammonium bisulfate, tricaprylylmethylammonium chloride (Aliquat 336), and the like.

In an embodiment, the process is carried out at temperature ranging from 0 to 180°C.

In an embodiment, the process is carried out at temperature ranging from 30°C to 150°C.

In an embodiment, the process is carried out at temperature ranging from 80°C to 120°C.

In an embodiment, the process is carried out for 1 to 10 hours.

In an embodiment, the process is carried out for 4 to 8 hours.

In an embodiment, the process further comprises a step of recovering the catalyst used in the process.
In an embodiment, the catalyst, the catalyst recovered in the process can be recycled and used for more than 3 cycles.
In an embodiment, the catalyst, the catalyst recovered in the process can be recycled and used for more than 5 cycles.
In an embodiment, the catalyst, the catalyst recovered in the process can be recycled and used for more than 10 cycles.
In an embodiment, the catalyst, the catalyst recovered in the process can be recycled and used for more than 20 cycles.
In an embodiment, the catalyst, the catalyst recovered in the process can be recycled and used for more than 25 cycles. According to an embodiment of the present invention, in the aminobiphenyl of formula (I), X1 and X2 are independently selected from hydrogen, bromine, chlorine, iodine or fluorine; Y is a protecting group; n is 0, 1, 2 or 3; and m is 0, 1 or 2.
According to an embodiment of the present invention, the aminobiphenyl of formula (I) is selected from compound of formula (Ia), (Ib) or salts thereof

wherein Y is a selected from hydrogen, a protecting group or a substituted pyrazole carbonyl group.
In an embodiment, Y is protecting group selected from group comprising of acyl, tosyl, mesyl, carbamate protecting group such as tert-butyloxycarbonyl, ethylcarbamate, benzyloxycarbonyl, benzene sulfonyl, p-nitrobenzene sulfonyl, trifluoro acetyl, tert-butyl sulfonyl, optionally substituted pyrazole acid, optionally substituted nicotinyl acid and the like.
In an embodiment, Y is acetyl group.
In an embodiment, compound of formula (Ia) is N-(3',4'-dichloro-5-fluorobiphenyl-2-yl) acetamide.
In an embodiment, compound of formula (Ib) is N-(3',4',5'-trifluoro[1,1'-biphenyl]-2-yl)acetamide.
In an embodiment, Y is hydrogen.
In an embodiment, the compound of formula (Ia) is 3',4'-dichloro-2-amino-5-fluorobiphenyl.
In an embodiment, the compound of formula (Ib) is 3,4,5-trifluoro-2'-aminobiphenyl.In an embodiment, Y is a substituted pyrazole carbonyl group.
In an embodiment, the compound of formula (Ia) is Bixafen.
In an embodiment, the compound of formula (Ib) is fluxapyroxad.
In an embodiment,
a) the boronic acid compound of formula (II) is selected from 3,4-dichlorophenylboronic acid or (3,4,5-trifluorophenyl)boronic acid;
b) the compound of formula (III) is selected from 2-bromo, 4-fluoro acetanilide, 2-bromo acetanilide, N-(2-bromo-4-fluorophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide or N-(2-bromophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide; and
c) aminobiphenyl of formula (I) is selected from N-(3',4'-dichloro-5-fluorobiphenyl-2-yl) acetamide, 3',4'-dichloro-2-amino-5-fluorobiphenyl, Bixafen, N-(3',4',5'-trifluoro[1,1'-biphenyl]-2-yl)acetamide, 3,4,5-trifluoro-2'-aminobiphenyl or fluxapyroxad.
In an embodiment, the salt of the compound of formula (I) is organic or inorganic salt.
In an embodiment, the salt of the compound of formula (I) is inorganic salt selected from hydrochloride, hydrobromide, hydroiodide, sulfate and the likes.
In an embodiment, the salt of the compound of formula (I) is hydrochloride salt.
In another embodiment, the compound of formula (I) wherein Y is protecting group is subjected to deprotection, to obtain compound of formula (I) wherein Y is hydrogen.
In another embodiment, N-(3',4'-Dichloro-5-fluorobiphenyl-2-yl) acetamide is subjected to deprotection to obtain 3',4'-Dichloro-2-amino-5-fluorobiphenyl.
In another embodiment, N-(3',4',5'-Trifluoro[1,1'-biphenyl]-2-yl)acetamide is subjected to deprotection to obtain 3,4,5-Trifluoro-2'-aminobiphenyl.
In another embodiment, the step of deprotection of the compound of formula (I) is optional.
In another embodiment, the step of deprotection of the compound of formula (I) is carried out by the processes known in prior art.In an embodiment, the step of deprotection of the compound of formula (I) wherein Y is protecting group, is carried out by treating the compound of formula (I) wherein Y is protecting group, with an acid and an alcohol.
In an embodiment, the acid used is mineral acid such as hydrochloric acid.
In an embodiment, the alcohol like methanol, ethanol, n-propanol, isopropanol, n-butanol, iso-butanol or mixtures thereof, are used.
In an embodiment, the alcohol used is methanol.
In an embodiment, the step of deprotection of the compound of formula (I) wherein Y is protecting group, is carried out by treating the compound of formula (I) wherein Y is protecting group, with a base.
The base used is selected from alkali or alkaline metal hydroxides, carbonates, bicarbonates or alkoxides.
The base used is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide sodium carbonate, potassium carbonate, lithium carbonate, calcium carbonate, sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, calcium bicarbonate, sodium alkoxide like sodium methoxide, sodium ethoxide, potassium alkoxide like potassium methoxide, potassium ethoxide and the like.
According to an embodiment of the present invention, there is provided a process for preparation of compound of formula (Ia) or salt thereof;

wherein Y is protecting group or hydrogen;
comprising steps of
i) reacting a boronic acid compound of formula (IIa) with a compound of formula (IIIa)

wherein Y is protecting group;
in presence of supported palladium catalyst obtain a compound of formula (Ia);
ii) optionally, deprotecting the compound of formula (Ia) wherein Y is protecting group; to obtain a compound of formula (Ia) wherein Y is hydrogen.
In an embodiment, in compound of formula (IIIa), Y is acetyl group.
In an embodiment, the compound of formula (Ia) or salt thereof, wherein Y is hydrogen or protecting group prepared according to the present invention, is used for preparation of Bixafen.
In an embodiment, the compound of formula (Ia) or salt thereof, wherein Y is hydrogen or protecting group prepared according to the present, is reacted with pyrazole acid chloride of formula (IV) to obtain Bixafen of formula (V).

In an embodiment, said reaction of compound of formula (Ia) or salt thereof wherein Y is hydrogen or protecting group, and pyrazole acid chloride of formula (IV) is carried out in presence of a base and an organic solvent.
The base used is selected from, but not limited to, base selected from alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates, bicarbonates or tertiary amines.
The base used is selected from, but not limited to, alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates or bicarbonates, such as, for example, sodium hydride, sodium amide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or caesium carbonate, and also tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, ?,?-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, ?,?-dimethylaminopyridine, diazabicyclooctane(DABCO), diazabicyclononene 25 (DBN) or diazabicycloundecene (DBU).
Preferably, N,N-dimethylaniline or triethylamine is used.
The amount of base used with respect to compound of formula (Ia) is in the range of 1 to 4 moles, preferably in the range of 2 to 3 moles.
In an embodiment, the organic solvent is selected from aliphatic, alicyclic or aromatic hydrocarbons; halogenated hydrocarbons; ethers; or amides.
The organic solvent used is selected from, but not limited to, aliphatic, alicyclic or aromatic hydrocarbons such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons such as, for example, chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1.2-dimethoxyethane, 1,2- diethoxyethane or anisole; alcohols such as methanol, ethanol, propanol, isopropanol, n-butanol, iso-butanol, tert-butanol; or amides, such as ?,?-dimethylformamide, N,N- dimethylacetamide, N-methylformanilide, N-methyl pyrrolidone or hexamethylphosphoric triamide.
In an embodiment, the organic solvent preferably is selected from aromatic hydrocarbons such as toluene or halogenated hydrocarbons such as dichloromethane.
In an embodiment, said reaction of compound of formula (Ia) or salt thereof, and pyrazole acid chloride of formula (IV) is carried out at temperature ranging from 0°C to 50°C.
Preferably, said reaction is carried out at room temperature.
More preferably said reaction is carried out at temperature ranging from 20 to 35°C.
In an embodiment, Bixafen is isolated by addition of water.
In another embodiment, Bixafen is isolated by addition of aqueous acid.
The acid used is selected from mineral acid, preferably hydrochloric acid is used.
According to an embodiment of the present invention, there is provided a process for preparation of compound of formula (Ib) or salt thereof,

wherein Y is protecting group;
comprising steps of
a) reacting a boronic acid compound of formula (IIb) with a compound of formula (IIIb)

wherein Y is protecting group;
in presence of supported palladium catalyst obtain a compound of formula (Ib);
ii) optionally, deprotecting the compound of formula (Ib) wherein Y is protecting group to obtain a compound of formula (Ib) wherein Y is hydrogen.
In an embodiment, in compound of formula (IIIb), Y is acetyl group.
In an embodiment, the compound of formula (Ib) or salt thereof prepared according to the present invention, is used for preparation of Fluxapyroxad.
In an embodiment, the compound of formula (Ib) or salt thereof, wherein Y is protecting group or hydrogen; is reacted with pyrazole acid chloride of formula (IV) to obtain Fluxapyroxad of formula (VI).

In an embodiment, said reaction of compound of formula (Ib) or salt thereof; and pyrazole acid chloride of formula (IV) is carried out in presence of a base and an organic solvent.
The base used is selected from, but not limited to, base selected from alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates, bicarbonates or tertiary amines.
The base used is selected from, but not limited to, alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates or bicarbonates, such as, for example, sodium hydride, sodium amide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or caesium carbonate, and also tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, ?,?-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, ?,?-dimethylaminopyridine, diazabicyclooctane(DABCO), diazabicyclononene 25 (DBN) or diazabicycloundecene (DBU).
Preferably, the base used in N,N-dimethylaniline.
In an embodiment, the amount of base used with respect to compound of formula (Ia) is in the range of 1 to 4 moles, preferably in the range of 2 to 3 moles.
In an embodiment, the organic solvent is selected from aliphatic, alicyclic or aromatic hydrocarbons; halogenated hydrocarbons; ethers; or amides.
The organic solvent used is selected from, but not limited to, aliphatic, alicyclic or aromatic hydrocarbons such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons such as, for example, chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1.2-dimethoxyethane, 1,2- diethoxyethane or anisole; alcohols such as methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, tert-butanol; or amides, such as ?,?-dimethylformamide, N,N- dimethylacetamide, N-methylformanilide, N-methyl pyrrolidone or hexamethylphosphoric triamide.
In an embodiment, the organic solvent preferably is selected from halogenated hydrocarbons such as dichloromethane.
In an embodiment, said reaction of compound of formula (Ib) and pyrazole acid chloride of formula (IV) is carried out at temperature ranging from 0°C to 50°C.
Preferably, said reaction is carried out at room temperature.
More preferably said reaction is carried out at temperature ranging from 20 to 35°C.
In an embodiment, Fluxapyroxad is isolated by addition of water.
In an embodiment, Fluxapyroxad is isolated by addition of an aqueous acid.
The acid used is selected from mineral acid, preferably hydrochloric acid is used.In an embodiment, Fluxapyroxad is recrystallized with an alcohol.
The alcohol used is selected from C1 to C5 alcohols, preferably methanol is used.In an embodiment, there is provided a process for preparation of a process for preparation of aminobiphenyl of formula (I) or salts thereof,

wherein, X1 and X2 are independently selected from hydrogen, chlorine, or fluorine; Y is a substituted pyrazole carboxamide group; n is 2 or 3; and m is 0 or 1; provided when X1 is chlorine, n is 2 or 3;
comprising steps of
i) reacting an organoboron compound of formula (II) with a compound of formula (III) in presence of a supported palladium catalyst to obtain a compound of formula (I) wherein Y is wherein Y is acetyl group; X1, X2, n and m are same as defined above;
ii) deprotecting the compound of formula (I) wherein Y is acetyl group; to obtain a compound of formula (I) wherein Y is hydrogen;
iii) reacting compound of formula (I) obtained in step ii) with pyrazole acid chloride of formula (IV) to obtain aminobiphenyl of formula (I) or salts thereof.
In an embodiment, the step i) is carried out in accordance with preferred embodiments as stated above.
In an embodiment, the step ii) of deprotection of the compound of formula (I) is carried out by the processes known in prior art.
In an embodiment, the step ii) is carried out by treating the compound of formula (I) wherein Y is acetyl group, with either an acid or a base.
In an embodiment, the acid is selected from a mineral acid; and the base is selected from alkali or alkaline metal hydroxides, carbonates, bicarbonates or alkoxides.
In an embodiment, the step iii) is carried out in presence of a base and an organic solvent.
The base used is selected from, but not limited to, base selected from alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates, bicarbonates or tertiary amines.
The base used is selected from, but not limited to, alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates or bicarbonates, such as, for example, sodium hydride, sodium amide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or caesium carbonate, and also tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, ?,?-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, ?,?-dimethylaminopyridine, diazabicyclooctane(DABCO), diazabicyclononene 25 (DBN) or diazabicycloundecene (DBU). Preferably, N,N-dimethylaniline or triethylamine is used.
The amount of base used with respect to compound of formula (I) is in the range of 1 to 4 moles, preferably in the range of 2 to 3 moles.
In an embodiment, the organic solvent is selected from aliphatic, alicyclic or aromatic hydrocarbons; halogenated hydrocarbons; ethers; or amides.
The organic solvent used is selected from, but not limited to, aliphatic, alicyclic or aromatic hydrocarbons such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons such as, for example, chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1.2-dimethoxyethane, 1,2- diethoxyethane or anisole; alcohols such as methanol, ethanol, propanol, isopropanol, n-butanol, iso-butanol, tert-butanol; or amides, such as ?,?-dimethylformamide, N,N- dimethylacetamide, N-methylformanilide, N-methyl pyrrolidone or hexamethylphosphoric triamide.
In an embodiment, the organic solvent preferably is selected from aromatic hydrocarbons such as toluene or halogenated hydrocarbons such as dichloromethane.
In an embodiment, step iii) is carried out at temperature ranging from 0°C to 50°C. Preferably, said reaction is carried out at room temperature. More preferably said reaction is carried out at temperature ranging from 20 to 35°C.
In one embodiment, the process for process for preparation of aminobiphenyl of formula (I) or salts thereof is carried out in one pot.
In an embodiment aminobiphenyl of formula (I) or salts thereof is Bixafen of formula (V) or Fluxapyroxad of formula (VI).
In an embodiment, there is provided a process for preparation of a process for preparation of Bixafen of formula (V) or salts thereof,

comprising steps of
i) reacting a boronic acid compound of formula (IIa) with a compound of formula (IIIa)

wherein Y is acetyl group
in presence of supported palladium catalyst obtain a compound of formula (Ia) or salt thereof;

ii) deprotecting the compound of formula (Ia) wherein Y is acetyl group; to obtain a compound of formula (Ia) wherein Y is hydrogen;
iii) reacting compound of formula (Ia) obtained in step ii) with pyrazole acid chloride of formula (IV) to obtain Bixafen of formula (V).

In an embodiment, said process for preparation of Bixafen of formula (V) is carried out in one pot.
According to an embodiment of the present invention, there is provided a process for preparation of Fluxapyroxad of formula (VI)

comprising steps of
i) reacting a boronic acid compound of formula (IIb) with a compound of formula (IIIb)

wherein Y is acetyl group;
in presence of supported palladium catalyst obtain a compound of formula (Ib) or salt thereof;

ii) deprotecting the compound of formula (Ib) wherein Y is protecting group to obtain a compound of formula (Ib) wherein Y is hydrogen;
iii) reacting compound of formula (Ib) obtained in step ii) with pyrazole acid chloride of formula (IV) to obtain Fluxapyroxad of formula (VI).

In an embodiment, said process for preparation of Fluxapyroxad of formula (VI) is carried out in one pot.
According to an embodiment of the present invention, the aminobiphenyl of formula (I) is selected from compound of formula (Ia), (Ib) or salts thereof, wherein Y is a substituted pyrazole carbonyl group.
In an embodiment, the compound of formula (Ia) is Bixafen of formula (V).
In an embodiment, the compound of formula (Ib) is Fluxapyroxad of formula (VI).
In an embodiment, there is provided a process for preparation of aminobiphenyl of formula (I) or salts thereof,

wherein, X1 and X2 are independently selected from hydrogen, chlorine, or fluorine; Y is a substituted pyrazole carbonyl group; n is 2 or 3; and m is 0 or 1; provided when X1 is chlorine, n is 2 or 3;
comprising steps of reacting an organoboron compound of formula (II)

wherein p is 2; q is 1; each Z is hydroxy group; X1 and n are same as defined above; or anhydride, dimer or trimer thereof;
with the compound of formula (III),

wherein X2 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; m is 0, 1 or 2; and Y is 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl group in presence of a supported palladium catalyst to obtain a compound of formula (I).
The base selected from alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates, bicarbonates or tertiary amines.
The base used is selected from, but not limited to, alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates or bicarbonates, such as, for example, sodium hydride, sodium amide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or caesium carbonate, and also tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, ?,?-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, ?,?-dimethylaminopyridine, diazabicyclooctane(DABCO), diazabicyclononene 25 (DBN) or diazabicycloundecene (DBU).
Preferably, N,N-dimethylaniline or triethylamine is used.
The organic solvent selected from aliphatic, alicyclic or aromatic hydrocarbons; halogenated hydrocarbons; ethers; or amides.
In an embodiment the organic solvent is selected from hydrocarbons such as aliphatic hydrocarbons, aromatic hydrocarbons or halogenated hydrocarbons.
The reaction of the organoboron compound of formula (II) with the compound of formula (III) is in accordance with the preferred embodiments stated above.
In an embodiment, the compound of formula (I) is Bixafen of formula (V) or Fluxapyroxad of formula (VI).
In an embodiment, there is provided a process for preparation of Bixafen of formula (V) or salts thereof,

comprising steps of reacting an organoboron compound of formula (IIa) with the compound of formula (IIIa),

wherein Y is 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl group in presence of a supported palladium catalyst to obtain Bixafen of formula (V).
In an embodiment, compound of formula (IIIa) wherein Y is 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl group can be represented as (IIIc) as below

In an embodiment, there is provided a process for preparation of Fluxapyroxad of formula (VI) or salts thereof,

comprising steps of reacting an organoboron compound of formula (IIb) with the compound of formula (IIIb),

wherein Y is 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl group in presence of a supported palladium catalyst to obtain Fluxapyroxad of formula (VI).
In an embodiment, compound of formula (IIIb) wherein Y is 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl group can be represented as (IIId) as below

All combinations of the present embodiments pertaining to the aspects described herein are specifically embraced by the present invention just as if each and every combination was individually explicitly recited, to the extent that such combinations embrace possible aspects. In addition, all sub-combinations of the embodiments contained within the aspects described herein.
EXAMPLES
The following examples are presented to provide what is believed to be the most useful and readily understood description of procedures and conceptual aspects of this invention. The examples provided below are merely illustrative of the invention and are not intended to limit the same to disclosed embodiments. Variations and changes obvious to one skilled in the art are intended to be within the scope and nature of the invention.

Example 1: Process for preparation of 3',4'-Dichloro-2-amino-5-fluorobiphenyl hydrochloride
To a mixture of 300ml of n-butanol, 42.15g of potassium carbonate, 16.37g of tetrabutylammonium bromide was added 48.5g of 3,4 – dichloro phenyl boronic acid and 56.03g of 2-bromo, 4-fluoro acetanilide. Then the reaction mass heated to 105-110°C followed by addition of 0.270g of 10% palladium on carbon. The reaction mass was then stirred for 5-6 hours at 105-110°C and then filtered to remove inorganic salt and catalyst. The filtrate obtained was concentrated then subjected to acetyl deprotection by treating with 64ml of concentrated hydrochloric acid in 126ml of methanol at 65-70°C for 3 to 4 hours. The mixture was then cooled to 0-5°C, the solid obtained was filtered and dried to get 62.5g of 3',4'-dichloro-2-amino-5-fluorobiphenyl hydrochloride with HPLC purity of 94.3%.
Example 2, 3 and 4: Process for preparation of 3',4'-dichloro-2-amino-5-fluorobiphenyl hydrochloride
The procedure of Example 1 was repeated using different catalysts. The results are given in the table below in which the catalysts are identified by example numbers as follows:
Example No. Catalyst used Mol % 3',4'-Dichloro-2-amino-5-fluorobiphenyl hydrochloride
(%)
2 Palladium hydroxide on carbon 1 79.86
3 Palladium on Barium sulfate 2 87.38
4 Palladium on calcium carbonate 2 83.12

Example 5: Process for preparation of Bixafen
To a mixture of 75g of 3',4'-Dichloro-2-amino-5-fluorobiphenyl hydrochloride as prepared in example 2, 375 ml of toluene 80.5 ml of N,N-dimethylaniline, was added 55.09g of pyrazole carboxylic acid chloride at 25-30°C. The reaction mixture formed was then maintained for 4-5 hours. After completion of the reaction, 91.2 ml of 6% hydrochloride solution was added and the mixture was stirred for 0.5 to 1 hour at 25 to 30°C. The mixture was then filtered, the wet cake obtained was washed sequentially with water and toluene, and dried to obtain 90g of Bixafen of formula (V) with HPLC purity of 98.74%
Example 6: Process for preparation of Bixafen
To a mixture of 650ml of n-butanol, 86.9g of potassium carbonate, 33.8g of tetrabutylammonium bromide was added 100g of 3,4 – dichloro phenyl boronic acid and 115.5g of 2-bromo, 4-fluoro acetanilide. Then the reaction mass heated to 100-110°C followed by addition of 0.55g of 10% palladium on carbon. The reaction mass was then stirred for 5-6 hours at 105-110°C. The mixture was then cooled to 60-65°C and filtered to remove inorganic salt and catalyst. The filtrate obtained was subjected to acetyl deprotection by treating with 120g of 48% sodium hydroxide solution at 110-115°C for 4 hours. To the mixture was then added 300ml water , the mixture was stirred for 0.5-1 hour and the layers were separated. To the organic layer was added 70.30g of N,N-dimethylaniline and 104.76g of pyrazole carboxylic acid, and the reaction mixture was maintained for 4-5 hours at 25-30°C. After completion of the reaction, of the reaction mixture was quenched with 30% hydrochloric acid and then stirred . The solid obtained was filtered, washed with water and butanol sequentially and dried to obtain 162g of Bixafen having HPLC purity of 97%.
Example 7: Process for preparation of 3,4,5-trifluoro-2'-aminobiphenyl hydrochloride
To a mixture of 545ml of n-butanol, 99.39g of 3,4,5-Trifluorophenyl boronic acid, 102.86g of 2-bromo acetanilide and 36.4g of tetrabutylammonium bromide, was added 93.7g of potassium carbonate. Then the reaction mass heated to 105-110°C followed by addition of 0.598g of 10% palladium on carbon. The reaction mass was then stirred for 5-6 hours at 105-110°C and then filtered to remove inorganic salt and catalyst. The filtrate obtained was concentrated then subjected to acetyl deprotection by treating with 129 ml of concentrated hydrochloric acid in 252 ml of methanol at 65-70°C for 3 to 4 hour. The mixture was then, filtered and dried to get 112g of 3,4,5-Trifluoro-2'-aminobiphenyl hydrochloride having 97% HPLC purity.

Example 8: Process for preparation of Fluxapyroxad
To 150ml of dichloromethane was added 50g of 3,4,5-trifluoro-2'-aminobiphenyl hydrochloride as prepared in example 7, 60.8 ml of N, N-dimethylaniline and 43.5g of pyrazole carboxylic acid chloride. The reaction mixture formed was then maintained at room temperature for 4-5 hours. After completion of reaction, reaction mixture was quenched with 30% hydrochloric acid and stirred at room temperature. The organic layer thus obtained was separated and concentrated to obtain crude product. The crude product obtained was recrystallized with methanol and dried to obtain 66g of Fluxapyroxad of formula (VI) with HPLC purity of 98.01%.

Example 9: Process for preparation of Fluxapyroxad
Step i) Preparation of N-(2-bromophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide:
To a mixture of 100 g of 2-bromo aniline and 692ml of toluene was slowly added 90ml of N,N dimethyl aniline followed by addition of 120.5g of 3-(di fluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl chloride. The mixture was then stirred for 2-3 hours at 25-30°C. After completion of reaction, the reaction mixture was quenched with 30% hydrochloric acid, filtered and washed with water. The isolated product dried to get 184 g N-(2-bromophenyl)-3-(difluoro methyl)-1-methyl-1H- pyrazole-4-carboxamide with HPLC purity more than 99%.

Step ii) Preparation of Fluxapyroxad:
To a mixture of 396ml of n-butanol, 55.3g of potassium carbonate, 21.5g of tetrabutylammonium bromide was added 100g of N-(2-bromophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide and 66.6g of 3,4,5-Trifluro phenyl boronic acid. Then the reaction mass heated to 105-110°C followed by addition of 0.35g of 10% palladium on carbon. The reaction mass was then stirred for 5-6 hours at 105-110°C, to the mixture was then added 200ml of water and then mixture was filtered to recover catalyst. The filtrate obtained was concentrated to get crude product. The crude mass was then recrystallized with methanol and dried to get 110g of Fluxapyroxad of formula (VI) with HPLC purity of more than 98%.

Example 10: Process for preparation of Bixafen
Step i) Preparation of N-(2-bromo-4-fluorophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide:
To a mixture of 31.68ml of 2-bromo aniline and 113ml of dichloromethane was slowly added 44ml of triethylamine followed by addition of 56.30g of 3-(di fluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl chloride. The mixture was then stirred for 2-3 hours at 25-30°C. After completion of reaction, the reaction mixture was quenched with 30% hydrochloric acid, filtered and washed with water. The isolated product was dried to get 80g N-(2-bromophenyl)-3-(difluoro methyl)-1-methyl-1H- pyrazole-4-carboxamide with HPLC purity more than 98%.
Step ii) Preparation of Bixafen:
To a mixture of 80ml of n-butanol, 9.61g of potassium carbonate, 3.69g of tetrabutylammonium bromide was added 20g of N-(2-bromo-4-fluorophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide and 11.1g of 3,4- dichloro phenyl boronic. Then the reaction mass heated to 105-110°C followed by addition of 0.061g of 10% palladium on carbon. The reaction mass was then stirred for 5-6 hours at 105-110°C, and then filtered to remove inorganic salt and catalyst. The filtrate obtained was concentrated to 20.9g of Bixafen having HPLC purity of more than 98%.
,CLAIMS:
1. A process for preparation of aminobiphenyl of formula (I) or salts thereof,

wherein, X1 and X2 are independently selected from hydrogen, bromine, chlorine, iodine or fluorine; Y is a selected from hydrogen, a protecting group or a substituted pyrazole carbonyl group; n is 0, 1, 2 or 3; and m is 0, 1 or 2; provided that when X1 is chlorine, n is 2 or 3;
comprising step of reacting an organoboron compound of formula (II)

wherein p is 2; q is 1; each Z is hydroxy group; X1 and n are same as defined above; or anhydride, dimer or trimer thereof
with a compound of formula (III)

wherein Y, X2 and m are same as defined above;
in presence of a supported palladium catalyst to obtain a compound of formula (I).

2. The process as claimed in claim 1, wherein
a) the boronic acid compound of formula (II) is selected from 3,4-dichlorophenylboronic acid or (3,4,5-trifluorophenyl)boronic acid;
b) the compound of formula (III) is selected from 2-bromo, 4-fluoro acetanilide, 2-bromo acetanilide, N-(2-bromo-4-fluorophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide or N-(2-bromophenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide; and
c) aminobiphenyl of formula (I) is selected from N-(3',4'-dichloro-5-fluorobiphenyl-2-yl) acetamide, 3',4'-dichloro-2-amino-5-fluorobiphenyl, Bixafen, N-(3',4',5'-trifluoro[1,1'-biphenyl]-2-yl)acetamide, 3,4,5-trifluoro-2'-aminobiphenyl or fluxapyroxad.

3. The process as claimed in claim 1, wherein the supported palladium catalyst is selected from metallic palladium, organic or inorganic palladium compounds.

4. The process as claimed in claim 1, wherein the supported palladium catalyst is selected from palladium on carbon, palladium hydroxide on carbon, palladium on barium sulfate or palladium on calcium carbonate.

5. The process as claimed in claim 1, wherein said reaction of the organoboron compound of formula (II) with a compound of formula (III) is carried out in presence of a solvent selected from water, ether, hydrocarbon, alcohol, ketone, amide or mixture thereof.

6. The process as claimed in claim 5, wherein said solvent is alcohol selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, iso-butanol or mixture thereof.

7. The process as claimed in claim 1, wherein said reaction of the organoboron compound of formula (II) with a compound of formula (III) is carried out in presence of a base selected from alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal carbonates, alkali metal bicarbonates, alkali metal and alkaline earth metal acetates, alkali metal and alkaline earth metal formates, alkali metal and alkaline earth metal alkoxides primary, secondary and tertiary amines, or mixtures thereof.

8. The process as claimed in claim 1, wherein said reaction of the organoboron compound of formula (II) with a compound of formula (III) is carried out in presence of a phase transfer catalyst selected from benzyltrialkylmmonium hydroxide, tetrabutylammonium hydroxide, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium chloride, cetyl trimethyl ammonium chloride, dodecyltrimethylammonium chloride, tetrabutyl ammonium bisulfate, tricaprylylmethylammonium chloride

9. A process for preparation of aminobiphenyl of formula (I) or salts thereof,

wherein, X1 and X2 are independently selected from hydrogen, chlorine, or fluorine; Y is a substituted pyrazole carbonyl group; n is 2 or 3; and m is 0 or 1; provided when X1 is chlorine, n is 2 or 3;
comprising steps of
i) reacting an organoboron compound of formula (II) with a compound of formula (III) in presence of a supported palladium catalyst to obtain a compound of formula (I) wherein Y is wherein Y is acetyl group; X1, X2, n and m are same as defined above;
ii) deprotecting the compound of formula (I) wherein Y is acetyl group; to obtain a compound of formula (I) wherein Y is hydrogen;
iii) reacting compound of formula (I) obtained in step ii) with pyrazole acid chloride of formula (IV) to obtain aminobiphenyl of formula (I) or salts thereof.

10. The process as claimed in claim 9, wherein the step ii) is carried out by treating the compound of formula (I) wherein Y is acetyl group, with either an acid or a base.

11. The process as claimed in claim 9, wherein the step iii) is carried out in presence of a base and an organic solvent.

12. The process as claimed in claim 11, wherein the base is selected from alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates, bicarbonates or tertiary amines.

13. The process as claimed in claim 11, wherein the organic solvent is selected from aliphatic, alicyclic or aromatic hydrocarbons; halogenated hydrocarbons; ethers; or amides.

14. The process as claimed in claim 9, wherein the process is carried out in one pot.

15. A process for preparation of aminobiphenyl of formula (I) or salts thereof,

wherein, X1 and X2 are independently selected from hydrogen, chlorine, or fluorine; Y is a substituted pyrazole carbonyl group; n is 2 or 3; and m is 0 or 1; provided when X1 is chlorine, n is 2 or 3;
comprising steps of reacting an organoboron compound of formula (II)

wherein p is 2; q is 1; each Z is hydroxy group; X1 and n are same as defined above; or anhydride, dimer or trimer thereof;
with the compound of formula (III),

wherein X2 is independently selected from hydrogen, bromine, chlorine, iodine or fluorine; m is 0, 1 or 2; and Y is 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl group in presence of a supported palladium catalyst to obtain a compound of formula (I).

16. The process as claimed in claim 9 or 15, wherein the compound of formula (I) is Bixafen of formula (V) or Fluxapyroxad of formula (VI).