Title of Invention

AN IMPROVED PROCESS FOR THE PREPARATION OF 2-ARYL PROPIONIC ACIDS

Abstract

An improved process for the preparation of 2-aryl propionic acids by carbonylating an aryl alkyl halide by containing palladium compound in an organic solvent selected from ketones, cyclic ethers in the carbon monoxide atmosphere under homogeneous conditions, at a temperature ranging between 30 to 130°C, for a period ranging between 0.3 to 4 hours, at pressures ranging between 50 to 1500 psig, cooling the reaction mixture to ambient temperature, flushing the reaction vessel with inert gas, removing the solvent by conventional methods, separating the catalyst and isolating 2-aryl propionic acid.

Full Text

This invention relates to an improved process for the preparation of 2-aryl propionic acids. Particularly, this invention relates to the improved process for conversion of arylalkyl halides having the general formula I wherein, RI may be aryl, substituted aryl, naphthyl or substituted naphthyl, R2, RS, R4 and R5 may independently be hydrogen, alkyl, aryl, arylalkyl, cycloaliphatic with or without substituents and X may be any of the halogen atoms such as chlorine, bromine, iodine, to the corresponding 2-aryl propionic acids using a homogeneous palladium catalyst system. A majority of the 2-aryl propionic acids are well-known non-steroidal anti-inflammatory drugs, Ibuprofen and Naproxen being two important examples. The conventional synthesis of ibuprofen involves six steps which use hazardous chemicals like cyanides and the waste materials produced require lot of down stream treatments for disposal. Recently, Hoechst Celanese Corporation has developed a novel environmentally benign three step catalytic process for the synthesis of ibuprofen, in which carbonylation of para isobutylphenyl ethanol (p-IBPE) is the key step. In the processes described in patented literature (EP 0,400,892A3, EP 0,284,310A1), the catalysts used were mainly Pd(PPh3)2Cl2 or PdCli or Pd (OAc)2 along with excess phosphine ligands in a biphasic system consisting of 10% aqueous HC1 as the promoter and p-IBPE dissolved in a solvent as the organic phase. The main drawback of this process is the lower reaction rates (TOP = 25-35 h-1) and lower selectivity to ibuprofen (56-69%) under mild conditions (130°C, lOOOpsig). Higher selectivity (>95 %) was obtained only at very high pressures of 2000 to 4500 psig of carbon monoxide and the rates still remained low. US patent 5,536,874 and the publication J. Chem. Tech. Biotecnol, 1997, 70, 83-91, describes the carbonylation of p-lBPE in a two-phase system wherein one phase is an aqueous medium which contains a water soluble palladium complex and an acid promoter. These processes also have disadvantages such as low reaction rates (TOF= 0.1 to 0.4 h-1) and lower ibuprofen selectivity (59-74%) under mild reaction conditions (90°C, 450 to 900 psig). The patents EP 0 338 852 and US 5 055 611, describes preparation of 2-arylpropionic acids by the carbonylation of aryl alkyl halides using PdCl2(PPh3)2 as the catalyst precursor along with 5% aq. HC1 as the promoter. In these cases also lower reaction rate and lower ibuprofen selectivity were achieved. The inventors of the present invention have observed that the use of a new homogeneous catalyst system comprising of a palladium compound, an organic acid and a halide promoters provide an improved catalyst system for the carbonylation of arylalkyl halides of general formula I to the corresponding 2-arylpropionic acids. The use of such a catalyst system gives high reaction rates and high selectivity to 2-arylpropionic acids under mild reaction conditions. The object of the present invention therefore is to provide an improved process for the preparation of 2-aryl propionic acids by the carbonylation of corresponding arylalkyl halides. Accordingly, the present invention provides an improved process for the preparation of 2-aryl propionic acids which comprises carbonylating an arylalkyl halide having the general formula I of the drawing accompanying the specification , wherein R1 is aryl, substituted aryl, naphthyl or substituted naphthyl, R2, R3, R4 and R5 are independently hydrogen, alkyl, aryl, arylalkyl or cycloaliphatic with or without substituents and X is any of the halogen atoms such as chlorine, bromine, iodine, a halide salts of the alkali metals an organic sulfonic acid, water and the catalyst, containing palladium compound in an organic solvent selected from ketones, cyclic ethers in the carbon monoxide atmosphere under homogeneous conditions, at a temperature ranging between 30 to 130°C, for a period ranging between 0.3 to 4 hours, at pressures ranging between 50 to 1500 psig, cooling the reaction mixture to ambient temperature, flushing the reaction vessel with inert gas, removing the solvent by conventional methods, separating the catalyst and isolating 2-aryl propionic acid of formula II of the drawing accompanying the specification wherein, RI is aryl, substituted aryl, naphthyl or substituted naphthyl, R2, R3, R4 and R5 are independently hydrogen, alkyl, aryl, arylalkyl, cycloaliphatic with or without substituents. In one of the embodiments of the present invention, the catalyst used may be any of the palladium (0) or palladium (II) compounds, such as palladium chloride, palladium bromide, palladium iodide, bis(triphenylphosphino) dichloro palladium (II), bis(triphenylphosphino) dibromo palladium(ll), bis(triparatolyphosphino) dichloro palladium(ll), bis(tricyclohexylphosphino) dichloro palladium(ll), bis(triethylphosphino) dichloro palladium(ll), bis(triisopropylphosphino) dichloro palladium(II), tetrakis(triphenylphosphino) palladium(O), dibenzylidieneacetonatopalladmm(O), cyclooctadiene dichloro palladium(II), bisbenzonitriledichoro palladium(II), acetylacetonato palladium(II) and bisacetonitrile dichloro palladium(II). In another embodiment the halide promoter may be any of the halide salts of alkali metals such as lithium chloride, sodium chloride, potassium chloride, lithium iodide, lithium bromide, sodium bromide, sodium iodide, potassium bromide, and potassium iodide or any of the quarternary ammonium or phosphonim halides such as tetrabutyl ammonium chloride, tetrabutyl ammonium bromide, tetrabutyl ammonium iodide, tetrabutyl phosphonium chloride, tetrabutyl phosphonium bromide or tetrabutyl phosphonium iodide. In yet another embodiment the organic acid used may be any of the organic sulphonic acids such as para toluene sulphonic acid, methane sulphonic acid or triflouromethane sulphonic acid. In yet another embodiment the organic solvent may be ketones like acetone, methyl ethyl ketone, methyl isobutyl ketone, diethyl ketone, methyl n-propyl ketone, acetophenone or cyclic ethers such as tetrahydrofuran, dioxan. In another embodiment the concentration of the catalyst may be one mole of catalyst for every 50 to 50000 moles of the compound having formula I, preferably 1 mole of catalyst for every 100 to 6000 moles of the compound having formula I and more preferably one mole of catalyst for every 150 to 2000 moles of compound having formula I. In still another embodiment the amount of halide per gram mole of the catalyst may be in the range of 5 to 500 moles, preferably 10 to 300 moles, and more preferably 25 to 150 moles. In another embodiment the amount of organic acid per gram mole of catalyst may be in the range of 5 to 500 moles, preferably 10 to 300 moles, and more preferably 25 to 150 moles. In yet another embodiment the amount of water may be in the range of 1 to 6 % (v/v) of the total reaction mixture, preferably 3 to 5 % (v/v). In a feature of the invention, the reaction can be conveniently carried out in a stirred reactor with the improved catalyst system employed with a suitable solvent in presence of carbon monoxide. In another feature of the invention the reaction can be carried out even at low pressures of carbon monoxide (upto 50 psig). In yet another feature of this invention, considerable enhancement in reaction rate and high selectivity towards 2-aryl propionic acids are obtained even under comparatively mild conditions. The improved process of the present invention is described herein below with examples, which are illustrative only and should not be construed to limit the scope of the present invention in any manner. EXAMPLE 1 A 50 ml stirred autoclave was charged with the following reactants l-(4'-isobutylphenyl) ethyl chloride: 0.02808mol PdCl2(PPh3)2: 5.6 x 10 -5mol p-toluene sulphonic acid : 0.0056 mol LiCl: 0.0056 mol H2O: 1.25mL Methyl ethyl ketone: 19mL The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115°C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of ibuprofen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the liquid phase analysed by gas chromatography. The GC analysis showed a turn over frequency (TOF) of 1120 h-1 and 99% conversion of l-(4'-isobutylphenyl) ethyl chloride with an ibuprofen selectivity of 95.2% and n/iso ratio of 0.05 . The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate was treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane, evaporation of the solvent and vacuum distillation gives the pure ibuprofen product. EXAMPLE 2 A 50 ml stirred autoclave was charged with the following reactants l-(4'-isobutylphenyl)ethyl chloride : 0.056179 mol PdCl2(PPh3)2:5.6x10-5mol p-toluene sulphonic acid : 0.0056 mol LiCl: 0.0056 mol H2O: 1.5mL Methyl ethyl ketone: 15 ml The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115°C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of ibuprofen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analysed by gas chromatography. The GC analysis showed TOF of 1350 h-1 and 99 % conversion of l-(4'-isobutylphenyl) ethyl chloride with an ibuprofen selectivity of 97% and n/iso ratio of 0.021. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate was treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase was separated which on hydrolysis with acid and extraction with ethyl acetate, evaporation and vacuum distillation gives the pure ibuprofen product. EXAMPLE 3 A 50 ml stirred autoclave was charged with the following reactants l-(4'-isobutylphenyl) ethyl bromide: 0.02808 mol PdBr2(PPh3)2: 5.6 x 10-5mol p-toluene sulphonic acid : 0.0056 mol LiBr: 0.0056 mol H2O: 1.25mL Methyl ethyl ketone: 19 ml The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115°C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of ibuprofen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analysed by gas chromatography. The GC analysis showed TOF of 940 h-1 and 99 % conversion of l-(4'-isobutylphenyl)ethyl bromide with ibuprofen selectivity of 95% and n/iso ratio of 0.052. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane, evaporation and vacuum distillation gives the pure ibuprofen product. EXAMPLE 4 A 50 ml stirred autoclave was charged with the following reactants l-(4'-isobutylphenyl) ethyl chloride: 0.02808 mol PdCl2(P-tolyl)3)2: 5.6 x 10 -5mol p-toluene sulphonic acid : 0.0056 mol LiCl: 0.0056 mol H2O: 1.25mL Methyl ethyl ketone: 19 mL The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115°C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of ibuprofen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analysed by gas chromatography. The GC analysis showed TOF of 1425 h-1 and 99% conversion of l-(4'-isobutylphenyl)ethyl chloride with ibuprofen selectivity of 95% and n/iso ratio of 0.052. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane, evaporation and vacuum distillation gives the pure ibuprofen product. EXAMPLE 5 A 50 ml stirred autoclave was charged with the following reactants sec-Phenethyl chloride : 0.05618 mol PdCl2(PPh3)2:5.6xl0-5mol p-toluene sulphonic acid : 0.0056 mol LiCl: 0.0056 mol H2O: 1.2mL Methyl ethyl ketone: 16 ml The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115°C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of 2-phenyl propionic acid, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analysed by gas chromatography. The GC analysis showed TOF of 1450 h-1 and 99% conversion of sec-phenethyl chloride with 2-phenyl propionic acid selectivity of 96.5% and n/iso ratio of 0.048. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane, evaporation and vacuum distillation gives the pure 2-phenyl propionic acid product. EXAMPLE 6 A 50 ml stirred autoclave was charged with the following reactants l-(6'-methoxy-2-naphthyl) ethyl chloride: 0.02808 mol PdCl2(PPh3)2:5.6x 10-5mol p-toluene sulphonic acid : 0.0056 LiCl: 0.0056 mol H2O: 1.25mL Methyl ethyl ketone: 19 mL The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115°C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of naproxen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analysed by gas chromatography. The GC analysis showed TOF of 425 h-1 and 99% conversion of l-(6'-methoxynaphthyl)chloride with naproxen selectivity of 97.5% and n/iso ratio of 0.025. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane and evaporation gives the pure naproxen product. EXAMPLE 7 A 50 ml stirred autoclave was charged with the following reactants l-(4'-isobutylphenyl) ethyl chloride : 0.0288 mol PdCl2(PPh3)2:5.6xl0-5mol p-toluene sulphonic acid : 0.0056 mol LiCl: 0.0056 mol H2O: 1.25 mL Methyl ethyl ketone: 19 mL The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115°C. After the temperature is attained, the autoclave was pressurised to 1200 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of ibuprofen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analysed by gas chromatography. The GC analysis showed TOF of 1600 h-1 and 99% conversion of l-(4'-isobutylphenyl) chloride with ibuprofen selectivity of 99 % and n/iso ratio of 0.01. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane, evaporation and vacuum distillation gives the pure ibuprofen product. EXAMPLE 8 A 50 ml stirred autoclave was charged with the following reactants l-(4'-isobutylphenyl) ethyl chloride: 0.0288 mol PdCl2(PPh3)2:5.6xl0-5acid : 0.0056mol LiCl: 0.0056 mol H2O: 1.25mL Methyl ethyl ketone: 16 mL The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115°C. After the temperature is attained, the autoclave was pressurised to 200 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of ibuprofen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analysed by gas chromatography. The GC analysis showed TOF of 220 h-1 and 99% conversion of l-(4'- isobutylphenyl) chloride with ibuprofen selectivity of 90% and n/iso ratio of 0.11. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane and column chromatography gives the pure ibuprofen product. EXAMPLE 9 A 50 ml stirred autoclave was charged with the following reactants l-(4'-isobutylphenyl) ethyl chloride : 0.0288 mol PdCl2(PPh3)2:5.6xl0-5mol p-toluene sulphonic acid : 0.0112mol LiCl: 0.0112 mol H2O: 1.25 mL Methyl ethyl ketone: 19 mL The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115°C. After the temperature is attained, the autoclave was pressurised to 1000 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of ibuprofen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the final reaction mixture analysed by gas chromatography. The GC analysis showed TOPF of 1450 h-1 and 99% conversion of l-(4'-isobutylphenyl) chloride with an ibuprofen selectivity of 97 % and n/iso ratio of 0.03. The solvent was evaporated and the reaction mixture was re-dissolved in toluene. The solid portion, which is a mixture of LiCl and lithium salt of p-toluene sulphonic acid was filtered out. The filtrate is treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane, evaporation and vacuum distillation gives the pure ibuprofen product. EXAMPLE 10 A 50 ml stirred autoclave was charged with the following reactants l-(4'-isobutylphenyl) ethyl chloride: 0.00562mol PdCl2(PPh3)2:5.6xl0-5mol p-toluene sulphonic acid : 2.8 x 10-4 mol H2O: 0.75 mL Methyl ethyl ketone: 23mL The contents of the autoclave were flushed with nitrogen and then many times with carbon monoxide. Thereafter, the contents were heated to 115°C. After the temperature is attained, the autoclave was pressurised to 800 psig with carbon monoxide, stirring started and it was observed that gas absorption commenced immediately. For synthesis of ibuprofen, the pressure in the autoclave was maintained constant using carbon monoxide and the progress of the reaction was monitored by observing the pressure drop and by liquid sampling. The reaction was continued until the pressure drop was too low. The reactor was then cooled and the liquid phase analysed by gas chromatography. The GC analysis showed a turn over frequency (TOF) of 125 h-1 and 99% conversion of l-(4'-isobutylphenyl) ethyl chloride with an ibuprofen selectivity of 96.8 % and n/iso ratio of 0.03. The solvent was evaporated and the reaction mixture was re-dissolved in toluene and the solid portion was filtered out. The filtrate was treated with saturated solution of sodium bicarbonate two-three times and the aqueous phase was separated which on hydrolysis with acid and extraction with dichloromethane, evaporation of the solvent and vacuum distillation gives the pure ibuprofen product. Advantages of the invention 1. Employment of a novel catalyst system under mild reaction conditions in a homogeneous medium 2. Provides high reaction rates and high productivity of 2-aryl propionic acids (2.5Kg/L/h) 3. Provides very high selectivity to 2-aryl propionic acids (90 to 99%)even under lower pressures of carbon monoxide (100 to 1200psig) We claim : 1. An improved process for the preparation of 2-aryl propionic acids which comprises carbonylating an arylalkyl halide having the general formula I of the drawing accompanying the specification , wherein R1 is aryl, substituted aryl, naphthyl or substituted naphthyl, R2, R3, R4 and R5 are independently hydrogen, alkyl, aryl, arylalkyl or cycloaliphatic with or without substituents and X is any of the halogen atoms such as chlorine, bromine, iodine, a halide salts of the alkali metals an organic sulfonic acid, water and the catalyst, containing palladium compound in an organic solvent selected from ketones, cyclic ethers in the carbon monoxide atmosphere under homogeneous conditions, at a temperature ranging between 30 to 130°C, for a period ranging between 0.3 to 4 hours, at pressures ranging between 50 to 1500 psig, cooling the reaction mixture to ambient temperature, flushing the reaction vessel with inert gas, removing the solvent by conventional methods, separating the catalyst and isolating 2-aryl propionic acid of formula II of the drawing accompanying the specification wherein, R-i is aryl, substituted aryl, naphthyl or substituted naphthyl, R2, Ra, RA and R5 are independently hydrogen, alkyl, aryl, arylalkyl, cycloaliphatic with or without substituents. 2. An improved process as claimed in claim 1 wherein the catalyst used is any of the palladium(O) or palladium(ll) compounds, such as palladium chloride, palladium bromide, palladium iodide, bis(triphenylphosphino) dichloro palladium(ll), bis(triphenylphosphino) dibromo palladium(ll), bis(tricyclohexylphosphino) dichloro palladium(ll), bis(triethylphosphino) dichloro palladium(ll), bis(triisopropylphosphino) dichloro palladium(ll), tetrakis(triphenylphosphino) palladium(O), dibenzylidieneacetonato palladium(O), cyclooctadiene dichloro palladium(ll), bis benzonitrile dichloro palladium (II), acetylacetonato palladium(ll) and bis acetonitrile dichloro palladium(ll). An improved process as claimed in claims 1 and 2 wherein halide salts of alkali metals are selected from lithium chloride, sodium chloride, potassium chloride, lithium iodide, lithium bromide, sodium bromide, sodium iodide, potassium bromide and potassium iodide or any of te quarternary ammonium or phosphonium halides such as tetrabutyl ammonium chloride, tetrabutyl ammonium bromide, tetrabutyl ammonium iodide, tetrabutyl phosphonium chloride, tetrabutyl phosphonium bromide or tetrabutyl phosphonium iodide. 3. An improved process as claimed in claims 1 to 3 wherein the organic acid used is any of the organic sulphonic acids are selected from para toluene sulphonic acid, methane sulphonic acid or triflouromethane sulphonic acid. 4. An improved process as claimed in claims 1 to 4 wherein the organic solvent is ketones selected from acetone, methyl ethyl ketone, methyl isobutyl ketone, diethyl ketone, methyl n-propyl ketone, acetophenone, N- methyl pyrrolidinone or cyclic ethers such as tetrahydrofuran, dioxin. 5. An improved process as claimed in claims 1 to 5 wherein the concentration of catalyst is one mole of catalyst for every 50 to 50000 moles of the compound having formula 1, preferably 1 mole of catalyst for every 100 to 6000 moles of the compound having formula 1 and more preferably one mole of catalyst for every 150 to 2000 moles of compound having formula 1. 7. An improved process as claimed in claims 1 to 6 wherein the amount of halide per gram mole of catalyst is in the range of 5 to 500 moles, preferably 20 to 300 moles and more preferably 50 to 150 moles. 8. An improved process as claimed in claims 1 to 7 wheein the amount of organic acid per gram mole of catalyst is in the range of 5 to 500 moles, preferably 20 to 300 moles, and more preferably 50 to 150 moles. 9. An improved process as claimed in claims 1 to 8 wherein the concentration of water is in the range of 1 to 6% (v/v) of the total reaction mixture, preferably 3 to 5% (v/v). 10. An improved process as claimed in claims 1 to 9 wherein the reaction can be carried out even at low pressures of carbon monoxide (upto 50 psig). 11. An improved process for the preparation of 2-aryl propionic acids as herein described with reference to the examples.

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571-del-1999-abstract.pdf

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571-del-1999-correspondence-others.pdf

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