Process for the preparation of unsaturated carboxylic acids by carbonylation of allyl alcohols and their acylation products

Abstract

The present invention relates to a process for carbonylating allyl alcohols at low temperature, low pressure and/or low catalyst loading. In an alternative embodiment, an acylation product of the allyl alcohol is used for the carbonylation. The present invention likewise relates to the preparation of conversion products of these carbonylation products and specifically of (−)-ambrox.

1 .- 27 . (canceled) 
     
     
         28 . A process for preparing a composition comprising at least one unsaturated carboxylic acid of the general formula (I) 
       
         
           
           
               
               
           
         
         or a salt thereof, in which 
         R 1  is hydrogen, linear or branched C 1 -C 24 -alkyl, linear or branched C 2 -C 24 -alkenyl having 1, 2, 3 or more than 3 C—C double bonds, unsubstituted C 5 -C 12 -cycloalkyl or C 5 -C 12 -cycloalkyl substituted by 1, 2 or 3 C 1 -C 6 -alkyl radicals or unsubstituted aryl or aryl substituted by 1, 2 or 3 C 1 -C 6 -alkyl radicals, 
         R 2  is hydrogen, linear or branched C 1 -C 24 -alkyl or linear or branched C 2 -C 24 -alkenyl having 1, 2, 3 or more than 3 C—C double bonds, or 
         R 1  and R 2  together with the carbon atom to which they are bonded are unsubstituted C 5 -C 7 -cycloalkyl or are C 5 -C 7 -cycloalkyl bearing 1, 2 or 3 linear or branched C 1 -C 6 -alkyl radicals, 
         in which an allyl alcohol selected from compounds of the general formulae (II.1) and (II.2) 
       
       
         
           
           
               
               
           
         
         is subjected to a carbonylation by reaction with carbon monoxide in the presence of a transition metal catalyst comprising at least one metal of groups 8, 9 and 10 of the Periodic Table of the Elements, wherein the reaction is additionally effected in the presence of at least one organic phosphorus compound as ligand and in the presence of a sub stoichiometric amount, based on the allyl alcohol, of a compound A) selected from anhydrides of aliphatic C 1 -C 12 -monocarboxylic acids, anhydrides of aliphatic C 4 -C 2 O-dicarboxylic acids, anhydrides of cycloaliphatic C 7 -C 70 -dicarboxylic acids, anhydrides of aromatic C 8 -C 2 O-dicarboxylic acids and acylated allyl alcohols of the formulae (III.1) and (III.2) 
       
       
         
           
           
               
               
           
         
         in which 
         R 3  is hydrogen, linear or branched C 1 -C 24 -alkyl, linear or branched C 2 -C 24 -alkenyl having 1, 2, 3 or more than 3 C—C double bonds, unsubstituted C 5 -C 12 -cycloalkyl or C 5 -C 12 -cycloalkyl substituted by 1, 2 or 3 C 1 -C 6 -alkyl radicals or unsubstituted aryl or aryl substituted by 1, 2 or 3 C 1 -C 6 -alkyl radicals, 
         R 4  is hydrogen, linear or branched C 1 -C 24 -alkyl or linear or branched C 2 -C 24 -alkenyl having 1, 2, 3 or more than 3 C—C double bonds, or 
         R 3  and R 4  together with the carbon atom to which they are bonded are unsubstituted C 5 -C 7 -cycloalkyl or are C 5 -C 7 -cycloalkyl bearing 1, 2 or 3 linear or branched C 1 -C 6 -alkyl radicals, 
         R 5  is C 1 -C 5 -alkyl, 
         and wherein the reaction is effected at a temperature of not more than 100° C. 
       
     
     
         29 . A process for preparing a composition comprising at least one unsaturated carboxylic acid of the general formula (I) 
       
         
           
           
               
               
           
         
         or a salt thereof, in which 
         R 1  is hydrogen, linear or branched C 1 -C 24 -alkyl, linear or branched C 2 -C 24 -alkenyl having 1, 2, 3 or more than 3 C—C double bonds, unsubstituted C 5 -C 12 -cycloalkyl or C 5 -C 12 -cycloalkyl substituted by 1, 2 or 3 C 1 -C 6 -alkyl radicals or unsubstituted aryl or aryl substituted by 1, 2 or 3 C 1 -C 6 -alkyl radicals, 
         R 2  is hydrogen, linear or branched C 1 -C 24 -alkyl or linear or branched C 2 -C 24 -alkenyl having 1, 2, 3 or more than 3 C—C double bonds, or 
         R 1  and R 2  together with the carbon atom to which they are bonded are unsubstituted C 5 -C 7 -cycloalkyl or are C 5 -C 7 -cycloalkyl bearing 1, 2 or 3 linear or branched C 1 -C 6 -alkyl radicals, 
         in which an acylated allyl alcohol selected from compounds of the general formulae (IV.1) and (IV.2) 
       
       
         
           
           
               
               
           
         
         in which R 6  is C 1 -C 5 -alkyl, 
         is subjected to a carbonylation by reaction with carbon monoxide in the presence of a transition metal catalyst comprising at least one metal of groups 8, 9 and 10 of the Periodic Table of the Elements, wherein the reaction is additionally effected in the presence of at least one organic phosphorus compound as ligand and in the presence of water and wherein the reaction is effected at a temperature of not more than 100° C. 
       
     
     
         30 . A process for preparing a composition comprising at least one unsaturated carboxylic acid of the general formula (I) 
       
         
           
           
               
               
           
         
         or a salt thereof, in which 
         R 1  is hydrogen, linear or branched C 1 -C 24 -alkyl, linear or branched C 2 -C 24 -alkenyl having 1, 2, 3 or more than 3 C—C double bonds, unsubstituted C 5 -C 12 -cycloalkyl or C 5 -C 12 -cycloalkyl substituted by 1, 2 or 3 C 1 -C 6 -alkyl radicals or unsubstituted aryl or aryl substituted by 1, 2 or 3 C 1 -C 6 -alkyl radicals, 
         R 2  is hydrogen, linear or branched C 1 -C 24 -alkyl or linear or branched C 2 -C 24 -alkenyl having 1, 2, 3 or more than 3 C—C double bonds, or 
         R 1  and R 2  together with the carbon atom to which they are bonded are unsubstituted C 5 -C 7 -cycloalkyl or are C 5 -C 7 -cycloalkyl bearing 1, 2 or 3 linear or branched C 1 -C 6 -alkyl radicals, 
         in which an allyl alcohol selected from compounds of the general formulae (II.1) and (II.2) 
       
       
         
           
           
               
               
           
         
         is subjected to a carbonylation by reaction with carbon monoxide in the presence of a transition metal catalyst comprising at least one metal of groups 8, 9 and 10 of the Periodic Table of the Elements, wherein the reaction is additionally effected in the presence of at least one organic phosphorus compound as ligand and in the presence of a sub stoichiometric amount, based on the allyl alcohol, of a compound B) 
       
       
         
           
           
               
               
           
         
         in which 
         R 10  and R 11 , independently of one another, are C 1 -C 6 -alkyl, C 1 -C 6 -fluoroalkyl or phenyl which is unsubstituted or substituted by a substituent selected from bromo, nitro and C 1 -C 4 -alkyl; 
         and wherein the reaction is effected at a temperature of not more than 100° C. 
       
     
     
         31 . The process according to  claim 30 , wherein the reaction is effected at a pressure of not more than 30 bar. 
     
     
         32 . The process according to  claim 30 , wherein the carbonylation is not effected in the presence of an added hydrohalic acid and not in the presence of an added alkali metal halide, alkaline earth metal halide or ammonium halide. 
     
     
         33 . The process according to  claim 30 , wherein the halide content of the reaction mixture of the carbonylation is not more than 2 mol %, preferably not more than 1 mol %, based on the total content of allyl alcohol of the general formulae (II.1) and (II.2) or based on the total content of esters of the general formulae (IV.1) and (IV.2). 
     
     
         34 . The process according to  claim 30 , wherein the compound A) is selected from acetic anhydride and allyl acetate. 
     
     
         35 . The process according to  claim 30 , wherein the compound A) used is an ester of the formula (III.1) or (III.2) that derives from the alcohol of the formula (II.1) or (II.2) used as the reactant for carbonylation. 
     
     
         36 . The process according to  claim 30 , in which the reaction is additionally effected in the presence of a nucleophilic reagent selected from 4-(di(C 1 -C 4 -alkyl)amino)pyridine, 4-(C 1 -C 4 -alkyl)pyridine and 4-(1-pyrrolidinyl)pyridine, preferably of 4-(dimethylamino)pyridine. 
     
     
         37 . The process according to  claim 36 , in which the nucleophilic reagent selected from 4-(di(C 1 -C 4 -alkyl)amino)pyridine, 4-(C 1 -C 4 -alkyl)pyridine and 4-(1-pyrrolidinyl)pyridine, is used in an amount of 0.01 to 5 mol %, preferably of 0.05 to 2 mol %, especially of 0.1 to 1 mol %, based on the total molar amount of the compounds (II.1) and (II.2). 
     
     
         38 . The process according to  claim 30 , in which the transition metal is used for the reaction in an amount of not more than 0.5 mol %, preferably of not more than 0.3 mol %, based on the total molar amount of the compounds (II.1) and (II.2), or based on the total molar amount of the compounds (IV.1) and (IV.2). 
     
     
         39 . The process according to  claim 30 , wherein the transition metal is selected from Pd, Ru, Rh, Ir and Fe, preference being given to using Pd as the transition metal. 
     
     
         40 . The process according to  claim 30 , wherein the organic phosphorus compound is selected from monodentate and bidentate phosphines, preferably from trialkylphosphines, triarylphosphines, dialkylarylphosphines, alkyldiarylphosphines, cycloalkyldiarylphosphines, dicycloalkylarylphosphines, tricycloalkylphosphines, triheterocyclylphosphines and trihetarylphosphines, the organic phosphorus compound used especially being triphenylphosphine, di-tert-butylphenylphosphine, cyclohexyldiphenylphosphine, dicyclohexylphenylphosphine, tri(p-tolyl)phosphine or tricyclohexylphosphine. 
     
     
         41 . The process according to  claim 30 , in which the total amount of the compound A) is not more than 50 mol %, preferably not more than 30 mol %, based on the total molar amount of the compound (II.1) and (II.2). 
     
     
         42 . The process according to  claim 30 , in which the reaction is additionally effected in the presence of a base other than the nucleophilic reagent selected from 4-(dimethylamino)-pyridine, 4-(C 1 -C 4 -alkyl)pyridine and 4-(1-pyrrolidinyl)pyridine, preferably in the presence of a basic N-heteroaromatic, of a trialkylamine, alkali metal carbonate or alkaline earth metal carbonate, especially of triethylamine. 
     
     
         43 . The process according to  claim 30 , in which the reaction is effected in the presence of an added aprotic organic solvent. 
     
     
         44 . The process according to  claim 30 , wherein the reaction is effected at a temperature of not more than 80° C., preferably of not more than 75° C. 
     
     
         45 . The process according to  claim 30 , wherein the reaction is effected at a pressure of not more than 25 bar, preferably of not more than 20 bar, especially of not more than 15 bar. 
     
     
         46 . The process according to  claim 30 , wherein the compound of the general formula (II.1) which is used for the reaction is selected from nerolidol, linalool, 3-methyl-1-penten-3-ol, 1-hepten-3-ol and 1-vinylcyclohexanol. 
     
     
         47 . The process according to  claim 30 , wherein E-nerolidol is used for the reaction. 
     
     
         48 . The process according to  claim 30 , in which E-nerolidol is subjected to a carbonylation, giving a reaction mixture comprising (3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid or a salt thereof and (3Z,7E)-4,8,12-trimethyl-trideca-3,7,11-trienoic acid or a salt thereof in a weight ratio of 80:20 to 50:50, preferably of 70:30 to 55:45. 
     
     
         49 . The process according to  claim 30 , wherein the compound of the general formula (II.2) used for the reaction is farnesol. 
     
     
         50 . The process according to  claim 30 , wherein the composition comprising the at least one unsaturated carboxylic acid of the formula (I) is an E/Z isomer mixture of the formula (I) comprising a 3-(E) acid of the formula (I-E) and a 3-(Z) acid of the formula (I-Z) 
       
         
           
           
               
               
           
         
         in which 
         R1 and R2 have different definitions and R1 has a higher priority according to IUPAC; 
         and this E/Z isomer mixture of the formula (I) is subjected to an enrichment of one isomer. 
       
     
     
         51 . The process according to  claim 50 , wherein the composition comprising the at least one unsaturated carboxylic acid of the formula (I) is an E/Z isomer mixture of the formula (I) comprising a 3-(E) acid of the formula (I-E) and a 3-(Z) acid of the formula (I-Z), in which, in addition,
 (1) the composition comprising the E/Z isomer mixture of the formula (I), in the presence of an alcohol and of a lipase enzyme, is subjected to an enzyme-catalyzed esterification, wherein the 3-(E) acid of the formula (I-E) is converted at least partly to a 3-(E) ester, so as to obtain a composition comprising the 3-(E) ester, unconverted 3-(E) acid of the formula (I-E) and unconverted 3-(Z) acid of the formula (I-Z);   (2) the composition obtained in (1) is separated to obtain a composition depleted of 3-(E) acid of the formula (I-E) and enriched in 3-(Z) acid of the formula (I-Z), and to obtain a composition comprising the 3-(E) ester;   (3) the composition obtained in (2) which is depleted of 3-(E) acid of the formula (I-E) and enriched in 3-(Z) acid of the formula (I-Z) is subjected to an isomerization to increase the content of 3-(E) acid of the formula (I-E); and   (4) optionally, the 3-(E) ester obtained in (2) is cleaved to obtain the 3-(E) acid of the formula (I-E).   
     
     
         52 . The process according to  claim 50 , wherein the composition comprising the at least one unsaturated carboxylic acid of the formula (I) is an E/Z isomer mixture of the formula (I) comprising a 3-(E) acid of the formula (I-E) and a 3-(Z) acid of the formula (I-Z), in which, in addition,
 (i) the composition comprising the E/Z isomer mixture of the formula (I) is subjected to an esterification in the presence of an alcohol to obtain the 3-(E) ester and the 3-(Z) ester;   (ii) the 3-(E) ester and the 3-(Z) ester obtained in (i) are subjected to a lipase-catalyzed enzymatic hydrolysis, wherein the lipase at least partly cleaves the 3-(E) ester to give the 3-(E) acid of the formula (I-E) to obtain a composition comprising the 3-(E) acid of the compound of the formula (I-E), unconverted 3-(E) ester and unconverted 3-(Z) ester;   (iii) the composition obtained in (ii) is separated to obtain a composition comprising the 3-(E) acid of the compound of the formula (I-E) and to obtain a composition comprising unconverted 3-(E) ester and unconverted 3-(Z) ester;   (iv) the composition which is obtained in (iii) and comprises unconverted 3-(E) ester and unconverted 3-(Z) ester is subjected to an ester cleavage to obtain a composition depleted of 3-(E) acid of the formula (I-E) or salt thereof and enriched in 3-(Z) acid of the formula (I-Z) or salt thereof; and   (v) the composition which is obtained in (iv) and is depleted of 3-(E) acid of the formula (I-E) and enriched in 3-(Z) acid of the formula (I-Z) is subjected to an isomerization to increase the content of 3-(E) acid of the formula (I-E).   
     
     
         53 . The process according to  claim 51 , wherein the isomerization to increase the content of 3-(E) acid of the formula (I-E) is effected in the presence of an anhydride of an organic acid and a base. 
     
     
         54 . A process for preparing (−)-ambrox (VIII) 
       
         
           
           
               
               
           
         
         in which 
         a1) a mixture of (3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid and (3Z,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid obtainable by the process as defined in  claim 30  is provided; 
         b1) the mixture of (3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid and (3Z,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid is subjected to a separation to obtain (3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid; 
         c1) the (3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid is subjected to a reduction to obtain (3E,7E)-homofarnesol (VI); 
         d1) the (3E,7E)-homofarnesol (VI) is subjected to a cyclization to obtain (−)-ambrox (VIII); 
         or 
         a2) a mixture of (3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid and (3Z,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid obtainable by the process as defined in  claim 30  is provided; 
         b2) the mixture of (3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid and (3Z,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid is subjected to a separation to obtain (3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid; 
         c2) the (3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienoic acid is subjected to a cyclization to obtain sclareolide (VII); 
         d2) the sclareolide (VII) is subjected to a reduction to obtain (−)-ambrox (VIII).