A process for the preparation of m-anisidine

Abstract

The present invention discloses an industrially feasible and environmentally friendly process for the preparation of m-anisidine (Formula I) from m-dinitrobenzene (Formula III). Further, the present invention discloses a process for the preparation of m-anisidine (Formula I) from m-nitroanisole (Formula II).

Description

[0001] “A PROCESS FOR THE PREPARATION OF M-ANISIDINE”

[0002] FIELD OF THE INVENTION:

[0003] The present invention relates to a process for the preparation of m- anisidine (Formula I). More particularly, the present invention relates to a process for the preparation of m-anisidine (Formula I) from m-dinitrobenzene (Formula III). Further, the present invention also relates to a process for the preparation of m-anisidine (Formula I) from m-nitroanisole (Formula II).

[0004] BACKGROUND OF THE INVENTION: m-Anisidine is an important organic intermediate, and widely used in the preparation of medicines such as aripiprazole, dyestuff and pigments, m-anisidine is generally prepared by the reduction of m-nitroanisole, wherein reduction is carried out by using reagents such as iron powder, disodium sulfide, sodium borohydride and hydrazine hydrate.

[0005] Tetrahedron, 1978, 34(14), 2057-2068 discloses the process for the preparation of m-nitroanisole in an organic solvent hexamethylphosphoramide (HMPA) and the target product is synthesized from m-dinitrobenzene, methanol and potassium phosphate as raw materials. The major drawback of this process is that the use of organic solvent hexamethylphosphoramide (HMPA) is expensive and thereby causes difficulties in post -treatment. HMPA has a high boiling point which causes the generation of byproducts, the post-treatment is inconvenient, and hence is not feasible to be used at industrial scale. Further, HMPA causes carcinogenesis. CN101250109 discloses a process for the synthesis of m-nitroanisole which comprises the methoxylation of m-dinitrobenzene in the presence of sodium methoxide in methanol solution in an autoclave in the presence of 18- crown-6-ether and tetrabutyl bromide catalysts. The main disadvantage is that the reaction is carried out at higher temperature (100 to 150°C) and pressure (5 to 10 bar). Further, the process employs 18-crown-6-ether as a co-catalyst which makes the process expensive.

[0006] CN108047067 discloses a method for preparing m-aminoanisole from m- nitroanisole in the presence of Pd / AhCh catalyst in a fluidized bed reactor.

[0007] The above processes as disclosed in the prior art for the preparation of m- nitroanisole from m-dinitrobenzene suffers from the drawbacks such as use of expensive reaction solvent such as HMPA, expensive reagents / co -catalysts such as 18-crown-6-ether and harsher reaction conditions which makes these processes less industrially favorable.

[0008] In industrial production, m-anisidine is mainly prepared from m- nitroanisole by using a disodium sulfide reduction method, however this process results in more environmental hazards.

[0009] Therefore, there is a need for an environmentally friendly, industrially feasible and cost effective alternate process for the synthesis of m-nitroanisole and m-anisidine which avoids the drawbacks as mentioned in the prior art.

[0010] Accordingly, the present invention provides a simple, industrially scalable and economical process for the preparation of m-anisidine through m-nitroanisole which is carried out using optimal reaction conditions, using the solvent and which obviates / minimizes the generation of waste, makes the process environmentally friendly and industrially safe.

[0011] OBJECTIVE OF THE INVENTION:

[0012] It is an objective of the present invention to ameliorate at least one of the drawbacks associated with the prior art.

[0013] The objective of the present invention is to provide a novel process for the preparation of m-anisidine (Formula I) from m-dinitrobenzene (Formula III).

[0014] Another objective of the present invention is to provide a novel process for the preparation of m-nitroanisole (Formula II) from m-dinitrobenzene (Formula III).

[0015] Yet another objective of the present invention is to provide a novel process for the preparation of m-anisidine (Formula I) from m-nitroanisole (Formula II).

[0016] Yet another objective of the present invention is to provide a process for the preparation of m-anisidine (Formula I) from m-dinitrobenzene (Formula III) which involves a process step being carried out at lower temperature and pressure reaction conditions.

[0017] Yet another objective of the present invention is to provide an environmentally friendly process for the preparation of m-anisidine (Formula I) from m-dinitrobenzene (Formula III) which involves a process step being carried out in the presence of suitable solvent. Other objects and advantages of the present invention will be more apparent from the following description which is not intended to Emit the scope of the present invention.

[0018] SUMMARY OF THE INVENTION:

[0019] The inventors of the present invention, surprisingly found that the methoxy lation reaction can be carried out at very low temperature and at ambient pressure as compared to prior arts which are carried out at high temperature and high pressure by using the appropriate solvent still results in the good yields and further does not require the co-catalyst.

[0020] Accordingly, the present invention provides a process for the preparation of m-anisidine (Formula I) from m-dinitrobenzene (Formula III) comprising the steps of: a) subjecting m-dinitrobenzene (Formula III) to a methoxylation reaction with a suitable methoxylation reagent in the presence of a suitable phase transfer catalyst and a first suitable solvent at a temperature in the range of 25 to 65°C and at ambient pressure to afford m-nitroanisole (Formula II); and b) subjecting m-nitroanisole (Formula II) of step (a) to a catalytic hydrogenation reaction in the presence of a suitable hydrogenation catalyst and a second suitable solvent under hydrogen atmosphere to afford m- anisidine (Formula I). The suitable methoxylation reagent in step (a) is selected from the group consisting of sodium methoxide, potassium methoxide, a mixture of methanol and sodium salt, a mixture of methanol and potassium salt and the like.

[0021] The suitable hydrogenation catalyst in step (b) is a noble metal-containing catalyst selected from the group consisting of palladium (Pd), platinum (Pt), Nickel (Ni). The suitable hydrogenation catalyst is optionally supported on a suitable carrier, wherein the suitable carrier is selected from the group consisting of carbon, alumina, silica, alumina-silica, carbon sulfides, and the like.

[0022] In one aspect, the present invention provides a process for the preparation of m-nitroanisole (Formula II) from m-dinitrobenzene (Formula III) comprising the step of subjecting m-dinitrobenzene (Formula III) to a methoxylation reaction with a suitable methoxylation reagent in the presence of a suitable phase transfer catalyst and a first suitable solvent to afford m-nitroanisole (Formula II).

[0023] In an exemplary embodiment of the present invention, the first suitable solvent is selected from the group consisting of ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dimethoxy ethane, 1,2-diethoxy ethane, anisole or aromatic hydrocarbon such as toluene, xylene, mixed xylenes or mixtures thereof.

[0024] In an exemplary embodiment of the present invention, the second suitable solvent is selected from the group consisting of ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dimethoxy ethane, 1,2-diethoxy ethane, anisole, methanol, ethanol, propanol, isopropanol, butanol or aromatic hydrocarbon such as toluene, xylene, mixed xylenes or mixtures thereof.

[0025] The first suitable solvent (step a) and the second suitable solvent (step b) is the same or different.

[0026] DESCRIPTION OF THE INVENTION:

[0027] References in the specification to "one embodiment" or "an embodiment" means that a particular feature, structure, characteristic, or function described in connection with the embodiment is included in at least one embodiment of the invention. The appearances of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment.

[0028] 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.

[0029] 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.

[0030] The terminology used, in the present disclosure, is only for the purpose of explaining a particular embodiment and such terminology shall not be considered to limit the scope of the present disclosure. The term “ambient pressure” as used herein refers to the pressure in the range of 0.950 bar and 1.050 bar.

[0031] 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.

[0032] 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.

[0033] 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.

[0034] The term “ambient pressure” as used herein, is the pressure in the 0.9 to 1.1 bar.

[0035] 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.

[0036] In line with the above defined objectives, the present invention provides a process for the preparation of m-anisidine (Formula I) from m-dinitrobenzene (Formula III) in two steps as depicted in the scheme I below.

[0037] The process is described in detail herein after.

[0038] In step a) m-dinitrobenzene (Formula III) is subjected to a methoxylation reaction with suitable methoxylation reagent, suitable phase transfer catalyst and the suitable solvent.

[0039] The said methoxylation reagent suitable for the said step a) is selected from the group consisting of sodium methoxide, potassium methoxide, a mixture of methanol and sodium salt, a mixture of methanol and potassium salt and the like.

[0040] Typically, the molar ratio of m-dinitrobenzene (Formula III) to a suitable methoxylation reagent is in the range of 1: 1 to 1:3. More particularly, the molar ratio of m-dinitrobenzene (Formula III) to a suitable methoxylation reagent is in the range of 1: 1 to 1:2.

[0041] The said phase transfer catalyst suitable for the said step a) is selected from the group consisting of tetraalkyl ammonium compounds, tetraphenyl ammonium compounds, tetraalkyl ammonium halides, tetraalkyl ammonium thiocyanates, tetraalkyl ammonium phosphates, tetraalkyl ammonium borates, tetraalkyl ammonium acetates, tetraalkyl ammonium sulfates, hexaalkyl ammonium halides and the like.

[0042] More particularly, the said phase transfer catalyst suitable for the said step (a) is selected from the group consisting of tetraalkyl ammonium compounds, tetraphenyl ammonium compounds or tetraalkyl ammonium halides and the like.

[0043] In one embodiment, said phase transfer catalyst suitable for the said step (a) is selected from the group consisting of tetramethylammonium chloride (TMAC), tetramethylammonium bromide (TMAB), tetramethylammonium hydroxide (TMAH), tetramethylammonium iodide (TMAI), tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride (TBAC), tetrabutylammonium hydroxide (TBAH), benzyltrimethylammonium chloride (BTMAC), dodecyltrimethylammonium bromide (DTAB) and tetraphenylphosphonium chloride (TPPC).

[0044] Typically, the loading of a phase transfer catalyst in a methoxylation reaction is in the range 1 to 20 w / w % with respect to m-dinitrobenzene (Formula

[0045] III). More particularly, the loading of a phase transfer catalyst in a methoxy lation reaction is in the range 8 to 18 w / w % with respect to m- dinitrobenzene (Formula III).

[0046] The said first suitable solvent suitable for the said step a) is selected from the group consisting of aliphatic, alicyclic or aromatic halogenated hydrocarbons such as monochlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane or trichloroethane; aromatic hydrocarbon like toluene, xylene or mixed xylenes; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2- methyltetrahydrofuran, 1,2-dimethoxy ethane, 1, 2-diethoxy ethane or anisole; nitriles such as acetonitrile, propionitrile, n- or iso-butyronitrile or benzonitrile; amides such as ^-di methyl formamide, iV-dimethylacetamide, A / - me thy I formanilide, tV-methylpyrrolidone; sulfoxides such as dimethyl sulfoxide or sulfones such as sulfolane; acetates such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl benzoate, ethyl benzoate, and butyl benzoate; ketones like acetone; water or mixtures thereof.

[0047] More particularly, the first suitable solvent is selected from the group consisting of ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2 -methyl tetrahydrofuran, 1,2-dimethoxy ethane, 1, 2-diethoxy ethane, anisole or aromatic hydrocarbon such as toluene, xylene, mixed xylenes or mixtures thereof.

[0048] Typically, the ratio of m-dinitrobenzene (Formula III) to a first suitable solvent is in the range 1: 20 w / w. More particularly, the ratio of m-dinitrobenzene (Formula III) to the first suitable solvent is in the range 1: 15 w / w.

[0049] The present method was developed to be an industrially feasible process for manufacturing m-anisidine at low pressures of ambient pressure conditions. The present method uses solvents that allows for dissolving reactants and reagents, and, thus, pressure can be reduced when compared to other prior art processes which use 5 bar or 10 bar pressure. The pressure employed is much lower as compared to the prior art. Less pressure is always beneficial for industrial amenability, as the equipment considerations for high pressure processes are significantly more complex and more expensive. The present method can be performed at lower temperatures of 25-65°C as compared to the prior art where temperatures are 100-150°C, thus making the present method even more industrially amenable. The inventors of the present invention surprisingly found that the better results and industrial amenability can be further achieved by employing the above parameters and further even without the need of co-catalyst.

[0050] In accordance with the process of the present invention, the yield of m- nitroanisole (Formula II) is in the range of 75 to 90%.

[0051] In step b) m-nitroanisole (Formula II) obtained in step (a) is subjected to a catalytic hydrogenation reaction in the presence of a suitable hydrogenation catalyst and a second suitable solvent under hydrogen atmosphere to afford m- anisidine (Formula I). The suitable hydrogenation catalyst in step (b) is a noble metal -containing catalyst selected from the group consisting of palladium (Pd), platinum (Pt), Nickel (Ni). The suitable hydrogenation catalyst is optionally supported on a suitable carrier, wherein the suitable carrier is selected from the group consisting of carbon, alumina, silica, alumina-silica, carbon sulfides, and the like.

[0052] The second suitable solvent as used in the process of present invention is selected from the group consisting of aliphatic, alicyclic or aromatic halogenated hydrocarbons such as monochlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane or trichloroethane; aromatic hydrocarbon like toluene, xylene or mixed xylenes; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dimethoxy ethane, 1, 2-diethoxy ethane or anisole; nitriles such as acetonitrile, propionitrile, n- or iso-butyronitrile or benzonitrile; amides such as A / , / V-di methyl formamide, N,N-dimethylacetamide, N-methyl formanilide, 2V-methylpyrrolidone or hexamethylphosphoric triamide; sulfoxides such as dimethyl sulfoxide or sulfones such as sulfolane; alcohols such as methanol, ethanol, propanol, isopropanol, butanol, polyethylene glycols; acetates such as methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl benzoate, ethyl benzoate, and butyl benzoate; ketones like acetone; water or mixtures thereof.

[0053] More particularly, the second suitable solvent is selected from the group consisting of ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dimethoxy ethane, 1,2-diethoxy ethane, anisole, methanol, ethanol, propanol, isopropanol, butanol or aromatic hydrocarbon such as toluene, xylene, mixed xylenes or mixtures thereof.

[0054] In an exemplary embodiment of the present invention, the process for the preparation of m-anisidine (Formula I) from m-dinitrobenzene (Formula III) comprises subjecting m-dinitrobenzene (Formula III) to a methoxylation reaction with a suitable methoxylation reagent such as sodium methoxide in the presence of a suitable phase transfer catalyst such as tetrabutylammonium bromide (TBAB) and a first suitable solvent such as 2-methyltetrahydrofuran to afford m- nitroanisole (Formula II) at a temperature in the range of 25-65°C for the period in the range of 6-18 h and at ambient pressure followed by subjecting m-nitroanisole (Formula II) to catalytic hydrogenation reaction in the presence of a suitable hydrogenation catalyst and a second suitable solvent under hydrogen atmosphere at a temperature in the range of 25-65°C and reaction pressure in the range of 2-40 bar to afford m-anisidine (Formula I).

[0055] In one embodiment, the molar ratio of m-nitroanisole (Formula II) to hydrogen is in the range of 1:2 to 1:4.

[0056] Typically, the molar ratio of m-nitroanisole (Formula II) to hydrogen is in the range of 1:3 to 1:4.

[0057] The loading of a hydrogenation catalyst in a catalytic hydrogenation reaction is in the range 1 to 10 w / w % with respect to m-nitroanisole (Formula II). The loading of a hydrogenation catalyst in a catalytic hydrogenation reaction is in the range 1 to 5 w / w % with respect to m-nitroanisole (Formula II).

[0058] In accordance with the process of the present invention, the m-anisidine of

[0059] Formula (I) is obtained in the yield ranging from 60 to 90 %.

[0060] In one embodiment, the present invention provides a process for the preparation of m-nitroanisole (Formula II) from m-dinitrobenzene (Formula III) comprises subjecting m-dinitrobenzene (Formula III) to a methoxylation reaction with a suitable methoxylation reagent in the presence of a suitable phase transfer catalyst and a first suitable solvent at a temperature in the range of 25-65°C for the period in the range of 6-18 h and at ambient pressure to afford m-nitroanisole (Formula II).

[0061] In another aspect of the present invention the process for the preparation m-nitroanisole (Formula II) from m-dinitrobenzene (Formula III) is as depicted in scheme II:

[0062] Formula IH Formula II

[0063] Scheme II In exemplary embodiment of the present invention, the present invention provides a process for the preparation of m-nitroanisole (Formula II) from m- dinitrobenzene (Formula III) comprises subjecting m-dinitrobenzene (Formula III) to a methoxylation reaction with a suitable methoxylation reagent such as sodium methoxide in the presence of a suitable phase transfer catalyst such as tetrabutylammonium bromide (TBAB) and a first suitable solvent such as 2- methyltetrahydrofuran to afford m-nitroanisole (Formula II).

[0064] In another embodiment a first suitable solvent is aromatic hydrocarbon selected from the group consisting of toluene, xylene, mix -xylene to afford m- nitroanisole (Formula II).

[0065] In one embodiment, m-nitroanisole (Formula II) is isolated or taken as such for the synthesis of m-anisidine (Formula I).

[0066] Typically, the methoxylation reaction is carried out at a temperature in the range of 25 to 65°C.

[0067] More particularly, the methoxylation reaction is carried out at ambient pressure.

[0068] Typically, the molar ratio of m-dinitrobenzene (Formula III) to a suitable methoxylation reagent is in the range of 1: 1 to 1:3.

[0069] More particularly, the molar ratio of m-dinitrobenzene (Formula III) to a suitable methoxylation reagent is in the range of 1: 1 to 1:2. Typically, the loading of a phase transfer catalyst in a methoxylation reaction is in the range 1 to 20 w / w % with respect to »r-di nitrobenzene (Formula III).

[0070] More particularly, the loading of a phase transfer catalyst in a methoxylation reaction is in the range 8 to 18 w / w % with respect to m- dinitrobenzene (Formula III).

[0071] In one aspect of the present invention, the ratio of m-dinitrobenzene (Formula III) to a first suitable solvent is in the range 1: 20 w / w.

[0072] In another aspect of the present invention, the ratio of m-dinitrobenzene (Formula III) to the first suitable solvent is in the range 1: 15 w / w.

[0073] In accordance with the process of the present invention, the yield of m- nitroanisole (Formula II) is in the range of 75 to 90%.

[0074] 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.

[0075] In one embodiment of the present invention, the m-nitroanisole (Formula II) is isolated or not isolated.

[0076] 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 workup is usually carried out by isolation of the product by filtration, quenching and optionally washing with a solvent, further optionally drying of the product if required. The isolation of the reaction product can also be carried out by a technique which includes but is not limited to decantation, centrifugation, evaporation, ultrafiltration, liquid-liquid extraction, distillation, recrystallization, chromatography, and the like.

[0077] EXAMPLES:

[0078] The invention is further illustrated with reference to the following examples. It is apparent to those skilled in the art that many modifications, both to materials, methods and various reaction parameters, may be practiced without departing from the scope of the invention. The starting materials according to the present invention are known compounds that are commercially available or can be prepared in a known manner. Following examples are given by way of illustration and therefore should not be construed to limit the scope of the invention.

[0079] Example 1: Preparation of m -nitroanisole (Formula II)

[0080] 166 gm of »z-di nitrobenzene was dissolved in 2-methyltetrahydrofuran at ambient temperature under nitrogen atmosphere. To this reaction mixture, 58.64 gm of sodium methoxide and 11.94 gm of Tetrabutylammonium bromide (TBAB) was added at ambient temperature. The temperature of the reaction mixture was raised to 45±5°C under the nitrogen atmosphere and the reaction mixture was stirred at a temperature at 45+5 °C for 6-18 h. After completion of the reaction, the reaction mass was filtered, washed with 2-methyltetrahydrofuran and the filtrate was concentrated under vacuum to afford m-nitroanisole (Yield: 85 %). The crude was purified using alcoholic solvent to afford pure m-nitroanisole.

[0081] Example 2: Preparation of m -nitroanisole (Formula II) 25 gm of m-dinitrobenzene was dissolved in toluene at ambient temperature under nitrogen atmosphere. To this reaction mixture, 10.4 gm of sodium methoxide and 2.40 gm of Tetrabutylammonium bromide (TBAB) was added at ambient temperature. The temperature of the reaction mixture was raised to 45±5°C under the nitrogen atmosphere and the reaction mixture was stirred at a temperature at 45+5 °C for 6-18 h. After completion of the reaction, the reaction mass was filtered, washed with toluene and the filtrate was concentrated under vacuum to afford m-nitroanisole (Yield: 86%). The crude was purified using alcoholic solvent to afford pure m-nitroanisole.

[0082] Similar experiments were carried out in the similar manner by using xylene as a solvent instead of toluene to obtain m-nitroanisole in the similar results.

[0083] Example 4: Preparation of m -A nisi dine (Formula I)

[0084] 100 gm of m-nitroanisole was dissolved in methanol in a 2 L autoclave at ambient temperature under nitrogen atmosphere. To this reaction mixture, 5 gm of Pt / C was added. A hydrogen pressure of 5 bar was applied and temperature was raised to 40°C. The reaction was maintained at 40-45°C and at 5-10 bar pressure till the completion of the reaction. After completion of the reaction, the reaction mass was cooled to ambient temperature. The reactor was flushed with nitrogen, the reaction mixture was unloaded and filtered through a celite bed and washed with methanol. The organic layer was concentrated and the resulting crude product was purified by distillation to afford pure m-anisidine (Formula I) (Yield:

[0085] 85 %). Example 5: Preparation of m -A nisi dine (Formula I)

[0086] 100 gm of m-nitroanisole was dissolved into methanol in a 2 L autoclave at ambient temperature under nitrogen atmosphere. To this reaction mixture, 5 gm of Raney nickel was added. A hydrogen pressure of 5 bar was applied and the temperature was raised to 40°C. The reaction was maintained at 40-45°C and at 5- 10 bar pressure till the completion of the reaction. After completion of the reaction, the reaction mass was cooled to ambient temperature. The reactor was flushed with nitrogen. Unload the reaction mixture, filtered through a celite bed and washed with methanol. The organic layer was concentrated and the resulting crude product was purified by distillation to afford pure m-anisidine (Formula I) (Yield: 90 %).

[0087] Comparative Example 1: Preparation of m -nitroanisole (Formula II) [Reference: CN101250109]

[0088] 2.5 gm of m-dinitrobenzene was dissolved in methanol at ambient temperature under the nitrogen atmosphere. To this mixture, 1.6 gm of sodium methoxide, 2.40 gm of Tetrabutylammonium bromide (TBAB) and 2.5 gm of 18 -crown-6 were added at ambient temperature. The temperature and pressure of the reaction mixture was raised to 80°C & 2.0 atm. respectively and agitated for 10 h. The progress of the reaction was monitored by GC. After completion of the reaction, the reaction mass was filtered, washed with methanol which resulted in 18% of m- nitroanisole, 49% of unknown high boiler impurity- 1 and 17% of high boiler unknown impurity-2. 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.

[0089] 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.

[0090] 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.

[0091] Various features and embodiments of the present invention are illustrated in the following representative examples, which are intended to be illustrative and non-limiting.

[0092] 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.

[0093] 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

CLAIMS:

1. A process for the preparation of m-anisidine (Formula I) from »z-di nitrobenzene(Formula III) comprising the steps of: a) subjecting »z-di nitrobenzene (Formula III) to a methoxy lation reaction with a suitable methoxylation reagent in the presence of a suitable phase transfer catalyst and a first suitable solvent at a temperature in the range of 25 to 65°C and ambient pressure to afford m-nitroanisole (Formula II); and b) subjecting m-nitroanisole (Formula II) of step (a) to a catalytic hydrogenation reaction in the presence of a suitable hydrogenation catalyst and a second suitable solvent under hydrogen atmosphere to afford m- anisidine (Formula I).

2. The process as claimed in claim 1, wherein said suitable methoxylation reagent is selected from the group consisting of sodium methoxide, potassium methoxide, a mixture of methanol and sodium salt, a mixture of methanol and potassium salt and the molar ratio of m-dinitrobenzene (Formula III) and the suitable methoxylation reagent is in the range of 1: 1 to 1:3.

3. The process as claimed in claim 1, wherein said suitable phase transfer catalyst in step (a) is selected from the group consisting of tetraalkyl ammonium compounds, tetraphenyl ammonium compounds, tetraalkyl ammonium halides, tetraalkyl ammonium thiocyanates, tetraalkyl ammonium phosphates, tetraalkyl ammonium borates, tetraalkyl ammonium acetates, tetraalkyl ammonium sulfates, hexaalkyl ammonium halides and the loading of a phase transfer catalystin the methoxylation reaction is in the range 1 to 20 w / w % with respect to m- dinitrobenzene (Formula III).

4. The process as claimed in claim 1, wherein said methoxylation reaction in step (a) is carried out at a temperature in the range of 25 to 65°C and at ambient pressure.

5. The process as claimed in claim 1, wherein said suitable hydrogenation catalyst in step (b) is a noble metal-containing catalyst selected from the group consisting of palladium (Pd), platinum (Pt), Nickel (Ni), and said hydrogenation catalyst is optionally supported on a suitable carrier selected from the group consisting of carbon, alumina, silica, alumina- silica and carbon sulfides.

6. The process as claimed in claim 1, wherein said first suitable solvent is selected from the group consisting of ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2- methyltetrahydrofuran, 1,2-dimethoxy ethane, 1,2-diethoxy ethane, anisole or aromatic hydrocarbon such as toluene, xylene, mixed xylenes and mixtures thereof.

7. The process as claimed in claim 1, wherein said second suitable solvent is selected from the group consisting of ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2- methyltetrahydrofuran, 1,2-dimethoxy ethane, 1,2-diethoxy ethane, anisole, methanol, ethanol, propanol, isopropanol, butanol or aromatic hydrocarbon such as toluene, xylene, mixed xylenes and mixtures thereof.

8. The process as claimed in claim 1, wherein the m-nitroanisole (Formula II) is not isolated.

9. The process as claimed in claim 1, wherein the yield of m-nitroanisole (FormulaII) is in the range of 75 to 90%.

10. The process as claimed in claim 1, wherein the overall yield of m-anisidine(Formula I) in two steps is in the range of 60 to 90%.

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