Process for producing substituted amino alcohols

Abstract

A process for producing a compound of the formula (I) involves at least reacting a compound of the formula (II) with hydrogen and water in the presence of at least one homogeneous transition metal catalyst TMC 1.

1 : A process for producing a compound of the formula (I) 
       
         
           
           
               
               
           
         
         wherein in the formula (I)
 R 1  is hydrogen or an organic radical having from 1 to 40 carbon atoms, 
 R 2  is an organic radical having from 1 to 40 carbon atoms, 
 or R 1  and R 2  together with the atoms connecting them, form a divalent organic group having from 1 to 40 carbon atoms, 
 
         the process comprising: 
         reacting a compound of the formula (II) 
       
       
         
           
           
               
               
           
         
         wherein in the formula (II)
 R 1  and R 2  have the same meaning as in formula (I), and 
 R 3  is hydrogen or an organic radical having from 1 to 40 carbon atoms, 
 
         with hydrogen and water in the presence of at least one homogeneous transition metal catalyst (TMC 1) comprising a transition metal selected from the group consisting of Ru and Rh. 
       
     
     
         2 : The process according to  claim 1 , wherein a ligand of the at least one homogeneous TMC 1 is selected from the group consisting of CO, H, Cl, and mono-, bi-, tri-, and tetra-dentate phosphines of the formulae (IV) and (V) 
       
         
           
           
               
               
           
         
         wherein 
         n is 0 or 1; 
         R 4  to R 12  are, independently of one another, unsubstituted or at least monosubstituted C 1 -C 10 -alkyl, C 1 -C 4 -alkyldiphenylphosphine (—C 1 -C 4 -alkyl-P(phenyl) 2 ), C 3 -C 10 -cycloalkyl, C 3 -C 10 -heterocyclyl comprising at least one heteroatom selected from the group consisting of N, O, and S, C 5 -C 14 -aryl, or C 5 -C 10 -heteroaryl comprising at least one heteroatom selected from the group consisting of N, O, and S, 
         wherein a substituent of R 4  to R 12  is selected from the group consisting of F, Cl, Br, OH, CN, NH 2 , and C 1 -C 10 -alkyl; 
         A is
 i) a bridging group selected from the group consisting of unsubstituted or at least monosubstituted N, O, P, C 1 -C 6 -alkane, C 3 -C 10 -cycloalkane, C 3 -C 10 -heterocycloalkane comprising at least one heteroatom selected from the group consisting of N, O, and S, C 5 -C 14 -aromatic, and C 5 -C 6 -heteroaromatic comprising at least one heteroatom selected from the group consisting of N, O, and S,
 wherein a substituent of the bridging group is selected from the group consisting of C 1 -C 4 -alkyl, phenyl, F, Cl, Br, OH, OR 16 , NH 2 , NHR 16 , and N(R 16 ) 2 , 
 wherein R 16  is selected from the group consisting of C 1 -C 10 -alkyl and C 5 -C 10 -aryl; or 
 
 ii) a bridging group of the formula (VI) or (VII): 
 
       
       
         
           
           
               
               
           
         
         
           
             wherein 
             m, q are, independently of one another, 0, 1, 2, 3, or 4; 
             R 13 , R 14  are, independently of one another, selected from the group consisting of C 1 -C 10 -alkyl, F, Cl, Br, OH, OR 15 , NH 2 , NHR 15 , and N(R 15 ) 2 , wherein R 15  is selected from the group consisting of C 1 -C 10 -alkyl and C 5 -C 10 -aryl; 
             X 1 , X 2  are, independently of one another, NH, O, or S; 
             X 3  is a bond, NH, NR 16 , O, S, or CR 17 R 18 ; 
             R 16  is unsubstituted or at least monosubstituted C 1 -C 10 -alkyl, C 3 -C 10 -cycloalkyl, C 3 -C 10 -heterocyclyl comprising at least one heteroatom selected from N, O and S, C 5 -C 14 -aryl, or C 5 -C 10 -heteroaryl comprising at least one heteroatom selected from the group consisting of N, O, and S, 
             wherein a substituent of R 16  is selected from the group consisting of F, Cl, Br, OH, CN, NH 2 , and C 1 -C 10 -alkyl; 
             R 17 , R 18  are, independently of one another, unsubstituted or at least monosubstituted C 1 -C 10 -alkyl, C 1 -C 10 -alkoxy, C 3 -C 10 -cycloalkyl, C 3 -C 10 -cycloalkoxy, C 3 -C 10 -heterocyclyl comprising at least one heteroatom selected from N, O, and S, C 5 -C 14 -aryl, C 5 -C 14 -aryloxy, or C 5 -C 10 -heteroaryl comprising at least one heteroatom selected from the group consisting of N, O, and S, 
             wherein a substituent of R 17  or R 18  is selected from the group consisting of F, Cl, Br, OH, CN, NH 2 , and C 1 -C 10 -alkyl; and 
           
         
         wherein in the formulae (IV) and (V) 
         Y 1 , Y 2 , Y 3  are, independently of one another, a bond, unsubstituted or at least monosubstituted methylene, ethylene, trimethylene, tetramethylene, pentamethylene, or hexamethylene, 
         wherein a substituent of Y 1 , Y 2 , or Y 3  is selected from the group consisting of F, Cl, Br, OH, OR 15 , CN, NH 2 , NHR 15 , N(R 15 ) 2 , and C 1 -C 10 -alkyl, 
         wherein R 15  is selected from the group consisting of C 1 -C 10 -alkyl and C 5 -C 10 -aryl. 
       
     
     
         3 : The process according to  claim 1 , wherein a ligand of the at least one homogeneous TMC 1 is selected from the group consisting of CO, H, Cl, PPh 3 , binap, PMe 3 , PEt 3 , Pn-Pr 3 , Pn-Bu 3 , Pn-Octyl 3 , 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), 1,1,1-tris(diphenylphosphinomethyl)ethane (Triphos), 1,2-bis(diphenylphosphino)ethane (dppe), P(Ph 2 )-Et-N-Et-P(Ph 2 ), P(Cy-)-Me-acridine-Me-(Cy 2 )P, and P(tBu 2 )-Me-pyridine-Me-P(tBu 2 ). 
     
     
         4 : The process according to  claim 1 , wherein R 3  is hydrogen. 
     
     
         5 : The process according to  claim 1 , wherein the at least one homogeneous TMC 1 is selected from the group consisting of [Ru(PPh 3 ) 3 (CO)(H)Cl], [Ru(PPh 3 ) 3 (CO)Cl 2 ], [Ru(PPh 3 ) 3 (CO)(H) 2 ], [Ru(binap)(Cl) 2 ], [Ru(PMe 3 ) 4 (H) 2 ], [Ru(PEt 3 ) 4 (H) 2 ], [Ru(Pn-Pr 3 ) 4 (H) 2 ], [Ru(Pn-Bu 3 ) 4 (H) 2 ], [Ru(Pn-Octyl 3 ) 4 (H) 2 ], [Ru(Pn-Bu 3 ) 4 (H) 2 ], [Ru(PnOctyl 3 ) 4 (H) 2 ], [Ru(PPh 3 ) 3 (CO)(H)Cl], [Ru(PPh 3 ) 3 (CO)(H) 2 ], Ru-MACHO, Ru-milst-acridine, Ru-milst-pyridine, and [Ru(PPh 3 ) 3 (CO)(H)Cl], in combination with 1,1,1-tris(diphenylphosphinomethyl)ethane (Triphos) or bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos). 
     
     
         6 : The process according to  claim 1 , wherein the at least one homogeneous TMC 1 is used in an amount of 0.001 mol % to 20 mol %, calculated as transition metal and based on the amount of the compound of the formula (II) used in the process. 
     
     
         7 : The process according to  claim 1 , wherein the reaction between the compound of the formula (II), water, and hydrogen is performed at a pressure in the range from 10 to 180 bar. 
     
     
         8 : The process according to  claim 1 , wherein the reaction between the compound of the formula (II), water, and hydrogen is performed at a temperature in the range from 50° C. to 180° C. 
     
     
         9 : The process according to  claim 1 , wherein the reaction between the compound of the formula (II), water, and hydrogen is performed in the presence of a solvent selected from the group consisting of an ether and an alcohol. 
     
     
         10 : The process according to  claim 1 , wherein the at least one homogeneous TMC 1 is recycled by removing the compound of the formula (II) and other volatile compounds of a reaction mixture obtained after the reaction between the compound of the formula (II), water, and hydrogen, via distillation. 
     
     
         11 : The process according to  claim 1 , wherein the reaction between the compound of the formula (II), water, and hydrogen is carried out at different H 2  pressures,
 wherein a lower H 2  pressure in the range from 1 to 80 bar is used at first to reduce the nitrile group of the compound of the formula (II), and afterwards H 2  pressure is increased to a pressure in the range from 90 to 200 bar to reduce the amide group of the compound of the formula (II).   
     
     
         12 : The process according to  claim 1 ,
 wherein the nitrogen-carbon bond of the amide group —N(H)—C(═O)— of a compound of the formula (III), which is formed as an intermediate product in the reaction between the compound of the formula (II), water, and hydrogen,   
       
         
           
           
               
               
           
         
         is cleaved by converting the amide group —NH—C(═O)—R 3  into an amino group —NH 2  or its corresponding ammonium group —NH 3   +  by hydrolysis or by hydrogenation of the amide group —NH—C(═O)—R 3  to form an amino group —NH 2  and a primary alcohol HO—CH 2 —R 3 . 
       
     
     
         13 : The process according to  claim 9 , wherein the solvent is selected from the group consisting of dioxane, tetrahydrofuran, glyme, methanol, and ethanol.