WO2005066109A1

WO2005066109A1 - A process for the preparation of 2-hydroxy carboxylic acids

Info

Publication number: WO2005066109A1
Application number: PCT/IB2003/006202
Authority: WO
Inventors: Raghunath Vitthal Chaudhari; Sunil Sopana Tonde
Original assignee: Council of Scientific and Industrial Research CSIR
Current assignee: Council of Scientific and Industrial Research CSIR
Priority date: 2003-12-26
Filing date: 2003-12-26
Publication date: 2005-07-21
Anticipated expiration: 2006-06-26
Also published as: AU2003298472A1; WO2005066109B1

Abstract

Two step preparation of hydroxy carboxylic acid (e.g. lactic acid) is achieved; Step 1) Carbonylating an enol ester (e.g. vinyl acetate) in presence of a hydroxyl compound (e.g. Methanol) using a palladium catalyst (e.g. PdCl2(PPh3)2), a O-, N- and/or P- containing ligand and a solvent, at 50-150°C/50-2000 psig to yield hydroxy ester (e.g. methyl lactate) and acetoxy ester (e.g. methyl-2-acetoxy propionate), separating and recycling the catalyst for carbonylation; Step 2) hydrolyzing the step 1 products to 2-hydroxy carboxylic acids (e.g. lactic acid) using acid catalysts (e.g. TsOH, aq HCl, resin) at 10-125°C, separating and recycling the catalyst for hydrolysis.

Description

A PROCESS FOR THE PREPARATION OF 2-HYDROXY CARBOXYLIC ACIDS

Field of the present invention

The present invention relates to a process for the preparation of 2-hydroxy carboxylic acids. Particularly the present invention relates to a process wherein an enol ester and a hydroxyl compound react with carbon monoxide in presence of a palladium catalyst, containing one or more ligands having one or more coordinating N, O and/ or P atoms and a solvent at a temperature and a pressure, to produce 2-acetoxy ester and/ or 2- hydroxy ester of corresponding carboxylic acid, of the corresponding carboxylic acid which on further catalytic hydrolysis produce 2-hydroxy carboxylic acid. The process has potential importance when applied to vinyl acetate. In a preferred embodiment vinyl acetate reacts with a hydroxyl compound and carbon monoxide to give 2-acetoxy propionic acid or 2-acetoxy propionate ester and/ or lactate ester, which can be converted to lactic acid on hydrolysis. Lactic acid is important commercially in baking industry, cheese industry, in dying wool, to make plasticisers for resin, etc. Background and prior art references of the present Application Lactic acid has been produced industrially by fermentation of molasses, but the process is costly and inefficient, and produces large amount of byproducts, making product separation and purification expensive. Another commercial rout for lactic acid is hydrocyanation of acetaldehyde followed by hydrolysis of cyanohydrin with H₂SO . This rout is highly corrosive, consumes stoichometric amount of toxic HCN and H SO . Further the process uses expensive HCN and produces stoichometric amount of (NH₄)₂SO₄. Alkoxycarbonylation of certain aceloxyolefmic compounds is reported in US patents 4,257,973 and 3,857,319. German patent 1,221,224 and Swiss patent 589,571 disclose carbonylation of alcohols or phenols with CO and olefins. However neither patent discloses the alkoxycarbonylation of enol acylates with CO and hydroxyl compound. US patent 4,072,709 provides a process for the production of lactic acid in which, alpha- aceloxy-propanaldehyde formed by hydroformylation of vinyl acetate is oxidized to alpha-aceloxy-propionic acid, which is further hydrolysed to lactic acid. However, the process involves three steps for the formation of lactic acid. US patent 4,377,708 provides a process for hydrocarbonylation of vinyl acetate using CO and water as reactants with vinyl acetate. In the process, special precautions are taken for the stability of the catalyst, reactants and products. The process needs to maintain the concentration of water not more than 3 weight percent of the medium, so as to avoid hydrolysis of reactant vinyl acetate to acetic acid and acetaldehyde. European patent 0144188 provides a process for alkoxycarbonylation of enol esters with hydroxyl compounds using Pd, Rh and Ni catalysts and further hydrolysis of the products to hydroxy acids. However, the process operates at low concentration of hydroxyl compound (<10 times of enol ester), further the process doesn't provide catalyst separation method and reuse, showing inefficiency of the catalyst. Palladium catalysed hydrocarbonylation of enol esters have been reported in Bull Chem. Soc. Jpn. 69, 1337-1345 (1996). However, the process needs high pressure of CO (150-250 atm.) and a base such as pyridine or its derivatives. Furthermore, loading of the catalyst is high (5 mol% of enol ester) which gives less activity in terms of turn over number. Also the process is applicable only for acetoxy esters and hydroxy esters, and not for the important product like hydroxy acids such as lactic acid.

As can be seen, the prior art processes suffer from several disadvantages such as use of costly and toxic chemicals, formation of large amount of byproducts, low catalyst activity, and catalyst and reactant stability. It is therefore necessary to develop a process for preparation of 2-hydroxy carboxylic acids, which overcomes the drawbacks enumerated above. Objects of the present invention

The main object of the present invention is to provide a process for the preparation of 2- hydroxy carboxylic acids, which overcomes the drawbacks of low activity, catalyst stability, use of toxic chemicals, and the severe operating conditions.

Another object of the invention is to provide an efficient catalytic process for the preparation of 2-hydroxy carboxylic acids via carbonylation of enol ester and subsequent hydrolysis of ester of the corresponding 2-acetoxy carboxylic acid and/ or ester of the corresponding 2-hydroxy carboxylic acid that operates at milder reaction condition. Still another object of the present invention is to provide the methods for catalyst separation and their reuse. Summary of the present invention

These and other objects of the present invention are achieved by providing a process comprising palladium in presence of one or more ligands containing coordinating nitrogen and/ or oxygen and/ or phosphorus atom/s catalysed carbonylation of enol ester in presence of a hydroxyl compound to yield 2-acetoxy ester and/or 2-hydroxy ester of the corresponding carboxylic acid at milder reaction conditions, which on further hydrolysis using acid catalysts to give 2-hydroxy carboxylic acid. In the process of the invention both carbonylation and hydrolysis catalysts are reusable. Detailed description of the present invention Accordingly the present invention provides a process for the preparation of 2-hydroxy carboxylic acids, which comprises; a) Carbonylation of an enol ester with carbon monoxide and a hydroxyl compound in presence of a palladium catalyst, an oxygen and/ or nitrogen and/ or phosphorus containing ligand(s) with molar ratio of 25:1,000 and a solvent at a temperature in the range of 50-250°C, at a pressure in the range of 50- 2000 psig, to obtain carbonylated ester; b) hydrolyzing the carbonylated ester with an acid catalyst at a temperature of 10- 125°C, to obtain 2-hydroxy carboxylic acid.

In another embodiment in the preparation of 2-hydroxy carboxylic acids the molar concentration ratio of enol ester/catalyst used is in the range of 25 to 1,000.

In yet other embodiment in the present invention the molar concentration ratio of hydroxyl compound/enol ester is not less than one.

In another embodiment the preparation of 2-hydroxy carboxylic acids the carbonylation catalyst is recycled and used for the carbonylation step. In one of the embodiment of the present invention the enol ester is an organic compound having formula R₁C=C(R₂)-O-Acyl, where R_t is H or an alkyl group containing 1-5 carbon atoms and R₂ is H or an alkyl group containing 1-5 carbon atoms.

In another embodiment, hydroxyl compound used is a compound having formula R-OH, where R is H or primary, secondary or tertiary alkyl group containing 1-7 carbon atoms selected from the group of compounds such as water, methanol, ethanol, propanol, iso- propanol, butanol, isobutanol, t-butanol, pentanol. In yet another embodiment of the present invention the catalyst used comprises palladium (II) or palladium (0) compound having formula ABxCy, where A stands for palladium, B is an organic ligand containing one or more coordinating nitrogen and/ or oxygen and/ or phosphorus atom/s and C is any halogen atom such as F, CI, Br or I and (x+y) is an integer ranging from 1 to 4, individually x and y can vary in the range of 0 to 4. Such palladium compounds can be selected from the group consisting of palladium chloride, palladium bromide, palladium iodide, and palladium acetate; or a metal complex of palladium such as bis(acetylacetonato)palladium(II), bis(triphenylphosphine)dichloropalladium(II), bis(triphenylphosphine)dibromopalladium (II), bis(triphenylphosphine)diiodopalladium (II), bis(pyridine)dichlorόpalladium(II), bis(pyridine)didromopalladium(II) , bis(pyridine)diiodopalladium(II) , bis(acetonotrile)dichloropalladium(ιι), bis(benzonitrile)dichloropalladi m(II), and tetrabis(triphenylphosphine)palladium(0). In another embodiment the ligand is a compound containing one or more coordinating O atom/s selected from the group such as acetyl acetonate, salicylaldehyde, p- toluenesulphonic acid, compounds containing one or more coordinating N atom/s such as pyridine, pipyridine, triethyl amine, tributyl amine, quinoliήe, isoquinoline, o- phenylenediamine, p-phenylenediamine, ethylenediamine, or coordinating N and O atoms such as 8-hydroxy quinoline, bis(saliylidene)ethylenediamine, salicylaldoxime, picolinic acid, nicotinic acid, anthranilic acid, one or more P containing compound such as trimethyl phosphine, triethyl phosphine, tri-n-butyl phosphine, tri-t-butyl phosphine, tricyclohexyl phosphine, triphenyl phosphine, bis(dicyclohexylphosphinoethane), bis(dicyclohexylphosphinobutane), bis(diphenylphosphinoethane), bis(diphenylphosphinopropane), bis(diphenylphosphinobutane), bis(diphenylphosphinohexane).

In yet another embodiment of the invention the solvent used is an organic solvent selected from toluene, benzene, chloroform, dichloromethane, dichloroethane, chlorobenzene, o-dichlorobenzene, p-dichlorobenzene or ketone selected from a group consisting of acetone, ethyl methyl ketone, diethyl ketone, acetophenone or a cyclic ether such as tetrahydrofuran, dioxan, or nitrile selected from acetonitrile, benzonitrile. In another embodiment the carbonylation product is separated by vacuum distillation or solvent extraction using appropriate solvent, and the carbonylation catalyst is recycled and reused for the carbonylation step.

In one of the embodiment, hydrolysis of carbonylation products is carried out with the catalyst selected from the group consisting acidic catalysts as p-toluene sulphonic acid, aq. Hydrochloric acid, or a resin like amberlite at a temperature in the range of 10-125°C; the catalyst can be separated by distillation or filtration and reused for hydrolysis. The invention will now be described with reference to the following examples, which are illustrated and should not be construed as limiting the scope of the invention in any manner. EXAMPLE 1 A 50 ml autoclave was charged with the following: Vinyl acetate: 0.025 mol Methanol: 0.060 mol PdCl₂(PPh₃)₂: 0.00005 mol Acetyl acetone: 0.001 mol Toluene: 20 ml

The contents of the autoclave were flushed thrice with carbon monoxide at room temperature. Thereafter, the contents were heated at 100°C. The autoclave was pressurized with carbon monoxide to 800 psig after the temperature was attained. The contents were stirred for 4 hours continuously. The reactor was then cooled to room temperature and the gas was vented off. The liquid contents were analysed by gas chromatography. The results of the gas chromatography showed 83.5 % conversion of vinyl acetate with 47.92 % selectivity to methyl-2-acetoxy propionate and 8.0 % selectivity to methyl lactate with turn over number of 210. (TON=Moles of the products hydrolysable to lactic acid per mole of the catalyst charged)

The product methyl-2-acetoxy propionate was characterized by 1H-NMR spectroscopy after separation by evaporating the low boilers and solvent and filtering out the precipitated catalyst. EXAMPLE 2 A 50 ml autoclave was charged with the following: Ninyl acetate: 0.025 mol Methanol: 0.060 mol PdCl₂(PPh₃)₂: 0.00005 mol Picolinic acid: 0.001 mol Toluςne: 20 ml

The contents of the autoclave were flushed thrice with carbon monoxide at room temperature. Thereafter, the contents were heated at 100°C. The autoclave was pressurized with carbon monoxide to 800 psig after the temperature was attained. The contents were stirred for 10 hours continuously. The reactor was then cooled to room temperature and the gas was vented off. The liquid contents were analysed by gas chromatography. The results of the gas chromatography showed 97.66% conversion of vinyl acetate with 61.42% selectivity to methyl-2-acetoxy propionate and 18.98%o selectivity to methyl lactate with turn over number of 399.4. EXAMPLE 3 Catalyst for recycle run was obtained by filtration after evaporating the low boilers and solvent f >m the reaction mixture of example 2 A 50 ml autoclave was charged with the following: Vinyl acetate: 0.025 mol Methanol: 0.060 mol Catalyst: recycled from example 2 Picolinic acid: 0.001 mol Toluene: 20 ml The contents of the autoclave were flushed thrice with carbon monoxide at room temperature. Thereafter, the contents were heated at 100°C. The autoclave was pressurized with carbon monoxide to 800 psig after the temperature was attained. The contents were stirred for 10 hours continuously. The reactor was then cooled to room temperature and the gas was vented off. The liquid contents were analysed by gas chromatography. The results of the gas chromatography showed 63.53% conversion of vinyl acetate with 38.08% selectivity to methyl-2-acetoxy propionate and 15.67% selectivity to methyl lactate. EXAMPLE 4 A 50 ml autoclave was charged with the following: Vinyl acetate: 0.025 mol Methanol: 0.060 mol PdCl₂(PPh₃)₂: 0.00005 mmol Nicotinic acid: 0.001 mol Toluene: 20 ml The contents of the autoclave were flushed thrice with carbon monoxide at room temperature. Thereafter, the contents were heated at 100°C. The autoclave was pressurized with carbon monoxide to 800 psig after the temperature was attained. The contents were stirred for 4 hours continuously. The reactor was then cooled to room temperature and the gas was vented off. The liquid contents were analysed by gas chromatography. The results of the gas chromatography showed 60.15% conversion of vinyl acetate with 57.57% selectivity to methyl-2 -acetoxy propionate and 16% selectivity to methyl lactate with turn over number of 227 EXAMPLE 5 A 50 ml autoclave was charged with the following: Vinyl acetate: 0.025 mol Methanol: 0.060 mol PdCl₂(PPh₃)₂ : 0.00005 mol Anthranilic acid: 0.001 mol Toluene: 20 ml The contents of the autoclave were flushed thrice with carbon monoxide at room temperature. Thereafter, the contents were heated at 100°C. The autoclave was pressurized with carbon monoxide to 800 psig after the temperature was attained. The contents were stirred for 10 hours continuously. The reactor was then cooled to room temperature and the gas was vented off. The liquid contents were analysed by gas chromatography. The results of the gas chromatography showed 98.9% conversion of vinyl acetate with 50.30% selectivity to methyl-2-acetoxy propionate and 20% selectivity to methyl lactate with turn over number of 356. EXAMPLE 6 A 50 ml autoclave was charged with the following: Vinyl acetate: 0.025 mol Methanol: 0.060 mol PdCl₂(PPh₃)₂: 0.00005 mol Pyridine: 0:001 mol /7-toluenesulphonic acid:0.0002 mol Toluene: 20 ml

The contents of the autoclave were flushed thrice with carbon monoxide at room temperature. Thereafter, the contents were heated at 100°C. The autoclave was pressurized with carbon monoxide to 800 psig after the temperature was attained. The contents were stirred for 4 hours continuously. The reactor was then cooled to room temperature and the gas was vented off. The liquid contents were analysed by gas chromatography. The results of the gas chromatography showed 99% conversion of vinyl acetate with 76.45% selectivity to methyl-2-acetoxy propionate with turn over number of 411. EXAMPLE 7 A 50 ml autoclave was charged with the following: Vinyl acetate: 0.025 mol Methanol: 0.060 mol PdCl₂(PPh₃)₂: 0.00005 mol Triphenylphosphine: 0.001 mol Toluene: 20 ml

The contents of the autoclave were flushed thrice with carbon monoxide at room temperature. Thereafter, the contents were heated at 100°C. The autoclave was pressurized with carbon monoxide to 800 psig after the temperature was attained. The contents were stirred for 8 hours continuously. The reactor was then cooled to room temperature and the gas was vented off. The liquid contents were analysed by gas chromatography. The results of the gas chromatography showed 99% conversion of vinyl acetate with 2% selectivity to methyl-2-acetoxy propionate with turn over number of 10. EXAMPLE 8 A 50 ml autoclave was charged with the following: Vinyl acetate: 0.025 mol Methanol: 0.060 mol PdCl₂(PPh₃)₂: 0.00005 mol p-toluenesulphonic acid:0.0002 mol Acetyl acetone: 0.001 mol Tetrahydrofuran: 20 ml

The contents of the autoclave were flushed thrice with carbon monoxide at room temperature. Thereafter, the contents were heated at 100°C. The autoclave was pressurized with carbon monoxide to 800 psig after the temperature was attained. The contents were stirred for 4 hours continuously. The reactor was then cooled to room temperature and the gas was vented off. The liquid contents were analysed by gas chromatography. The results of the gas chromatography showed 91.43% conversion of vinyl acetate with 35.67% selectivity to methyl-2-acetoxy propionate and 25.65% selectivity to methyl lactate with turn over number of 295. EXAMPLE 9 A 50 ml autoclave was charged with the following: Vinyl acetate: 0.025 mol Methanol: 0.060 mol ^• PdCl₂(PPh₃)₂: 0.00005 mol Acetyl acetone: 0.001 mol p-toluenesulphonic acid:0.0002 mol Acetonitrile: 20 ml

The contents of the autoclave were flushed thrice with carbon monoxide at room temperature. Thereafter, the contents were heated at 100°C. The autoclave was pressurized with carbon monoxide to 800 psig after the temperature was attained. The contents were stirred for 4 hours continuously. The reactor was then cooled to room temperature and the gas was vented off. The liquid contents were analysed by gas chromatography. The results of the gas chromatography showed 82.65%) conversion of vinyl acetate with 4%> selectivity to methyl-2-acetoxy propionate and 42.56% selectivity to methyl lactate with turn over number of 202. EXAMPLE 10 A 50 ml autoclave was charged with the following: Vinyl acetate: 0.025 mol Methanol: 23 ml PdCl₂(PPh₃)₂: 0.00005 mol Acetyl acetone: 0.001 mol The contents of the autoclave were flushed thrice with carbon monoxide at room temperature. Thereafter, the contents were heated at 100°C. The autoclave was pressurized with carbon monoxide to 800 psig after the temperature was attained. The contents were stirred for 3 hours continuously. The reactor was then cooled to room temperature and the gas was vented off. The liquid contents were analysed by gas chromatography. The results of the gas chromatography showed 91.26%> % conversion of vinyl acetate with 3% selectivity to methyl-2-acetoxy propionate with turn over number of 10.97. EXAMPLE 11 , Methyl lactate was separated by extracting with 15 ml water from the reaction mixture of example 3, to which 1 ml of cone. HCl was added. Thereafter, the reaction mixture was refluxed for 3 hours. The contents were analysed by gas chromatography after cooling the reaction mixture. The results showed 58 % conversion of methyl lactate.

EXAMPLE 12

^• 0.191 g of p-toluene sulphonic acid and 15 ml water was added to 1.46 g of methyl-2- acetoxy propionate. Thereafter, the reaction mixture was refluxed for 3 hours and the contents were analysed by gas chromatography after cooling the reaction mixture. The analysis showed 100% conversion of methyl-2-acetoxy propionate with 100% selectivity to lactic acid. EXAMPLE 13 15 ml of water and O.lg of amberlite IR 20 resin were added to the reaction mixture of example 4. Thereafter, the contents were heated to 80°C. for 3 hours. The contents were analysed by gas chromatography. The analysis showed 17.33% conversion of methyl-2- acetoxy propionate. EXAMPLE 14

The catalyst from example 13 was separated by filtration and added to 1.44 g of methyl- 2-acetoxy propionate and 15 ml water. Thereafter the contents were heated to 80°C for 3 hours. The analysis was done by gas chromatography. The results showed 41.77% conversion of methyl-2-acetoxy propionate with 100 % selectivity to lactic acid. ADVANTAGES OF THE INVENTION

1. The process of the invention provides an alternative catalytic system for the production of lactic acid, which is economic and efficient.

2. The process provides the method for catalyst separation and its reuse.

3. The process operates at milder reaction conditions.

Claims

We claim:

1. An efficient process for the preparation of 2-hydroxy carboxylic acids using reusable catalyst, said process comprises the steps of, a. Carbonylation of an enol ester with carbon monoxide and a hydroxyl compound in presence of a palladium catalyst, an oxygen and/ or nitrogen and/ or phosphorus containing ligand(s) with molar ratio of 25:1,000 and a solvent at a temperature in the range of 50-250°C, at a pressure in the range of 50- 2000 psig, to obtain carbonylated ester; b. hydrolyzing the carbonylated ester with an acid catalyst at a temperature of 10-125°C, to obtain 2-hydroxy carboxylic acid.

2. A process as claimed in claim 1, wherein the molar concentration ratio of hydroxyl compound/enol ester is not less than one.

3. A process as claimed in claim 1, wherein the carbonylation catalyst is recycled and used for the carbonylation step.

4. A process as claimed in claim 1, wherein enol ester is an organic compound having formula RjC=C(R₂)-O-Acyl, where R_\ is H or an alkyl group containing 1-5 carbon atoms and R is H or an alkyl group containing 1-5 carbon atoms.

5. A process as claimed in claim 1, wherein hydroxyl compound used is a compound having formula R-OH, where R is H or a primary, secondary or tertiary alkyl group containing 1-7 carbon atoms selected from the group of compounds such as water, methanol, ethanol, propanol, iso-propanol, butanol, iso-butanol, t-butanol and pentanol.

6. A process as claimed in claim 1, wherein the catalyst is selected from palladium (II) or palladium (0) compound having formula ABxCy, where A = palladium, B = organic ligand containing one or more coordinating nitrogen and/ or oxygen and/ or phosphorus atom/s and, C = any halogen atom such as F, CI, Br or I and (x+y) is an integer ranging from 1 to 4, individually x and y can vary in the range of 0 to 4.

7. A process as claimed in claim 1 palladium catalyst can be selected from the group consisting of palladium chloride, palladium bromide, palladium iodide, and palladium acetate; or a metal complex of palladium such as bis(acetylacetonato)palladium(II), bis(triphenylphosphine)dichloropalladium(II), bis(triphenylphosphine)dibromopalladium (II), bis(triphenylphosphine)diiodopalladium (II), bis(pyridine)dichloropalladiunι(II), bis(pyridine)didromopalladium(II), bis(pyridine)diiodopalladium(II), bis(acetonotrile)dichloropalladium(II), bis(benzonitrile)dichloropalladium(II), and tetrakis(triphenylphosphine)palladium(0).

8. A process as claimed in claim 1, wherein the ligand is a compound containing one or more coordinating O atom(s) selected from the group consisting of acetyl acetonate, salicylaldehyde, p-toluenesulphonic acid; compounds containing one or more coordinating N atom/s such as pyridine, pipyridine, triethyl amine, tributyl amine, quinoline, isoquinoline, o-phenylenediamine, p-phenylenediamine, ethylenediamine, or coordinating N and O atoms such as 8-hydroxy quinoline, bis(saliylidene)ethylenediamine, saUcylaldoxime, picolinic acid, nicotinic acid, anthranilic acid; one or more P containing compound such as trimethyl phosphine, triethyl phosphine, tri-n-butyl phosphine, tri-t-butyl phosphine, tricyclohexyl phosphine, triphenyl phosphine, bis(dicyclohexylphosphinoethane), bis(dicyclohexylphosphinobutane), bis(diphenylphosphinoethane), bis(diphenylphosphinopropane), bis(diphenylphosphinobutane), and bis(diphenylphosphinohexane).

9. A process as claimed in claim 1, wherein the solvent used is an organic solvent selected from the group of solvents containing toluene, benzene, chloroform, dichloromethane, dichloroethane, chlorobenzene, o-dichlorobenzene, p- dichlorobenzene or ketone selected from a group consisting of acetone, ethyl methyl ketone, diethyl ketone, acetophenone or a cyclic ether such as tetrahydrofuran, dioxan, or nitrile selected from acetonitrile and benzonitrile.

10. A process as claimed in claim 1 wherein the product is separated by vacuum distillation or solvent extraction.

11. A process as claimed in claim 1, wherein hydrolysis of carbonylation products is carried out with the catalyst selected from the group consisting of acidic catalysts as p-toluene sulphonic acid, aq. Hydrochloric acid, or a resin like amberlite, separated by distillation or filtration and reused for hydrolysis.

12. A process as claimed in claim 1, wherein the hydrolysis catalyst is recycled and used for the hydrolysis step.