Selective Splitting of Substituted Bisbenzylamides and Bisbenzylamines

Abstract

A process for the regioselective cleavage of secondary amines or amides is described.

1 . A process for the regioselective cleavage of secondary amines or amides, which comprises the following process steps: 
 (a′) provision of at least one secondary bisbenzylamine or bisbenzylamide having at least one benzylic hydrogen atom in a solvent;    (b′) electrochemical oxidation of the secondary amine or amide in the presence of an electrolyte salt and reaction of the electrolysis intermediate with a nucleophile, giving an electrolysis product mixture;    (c′) work-up of the electrolysis product mixture;    (d′) hydrolysis of the workup electrolysis product mixture.    
     
     
         2 . (canceled)  
     
     
         3 . The process according to  claim 1 , wherein at least one benzyl ring of the bisbenzylamines or bisbenzylamides is substituted by an electron-pushing substituent which exerts a +I effect and/or a +M effect on the benzyl ring.  
     
     
         4 . The process according to  claim 1 , wherein a nucleophilic solvent selected from the group consisting of methanol, ethanol, n-propanol, i-propanol and butanol is used in process step (a).  
     
     
         5 . The process according to  claim 1 , wherein the electrochemical oxidation is carried out under at least one of the following conditions: 
 a temperature of from −20 to 60° C.;    a current density of from 1 to 1000 mA/cm 2 ;    a concentration of the electrolyte salt of from 0.0001 to 5 mol/l.    
     
     
         6 . The process according to any of  claim 1 , wherein the electrolysis solution is worked up as follows in (c′): 
 (c′1) removal of the solvent and addition of water, an organic solvent selected from the group consisting of dichloromethane, chloroform, ethers, esters and hydrocarbons, and an acid;    (c′2) extraction of the mixture resulting from process step (c′1) with an organic solvent selected from the group consisting of dichloromethane, chloroform, ethers, esters and hydrocarbons;    (c′3) drying of the resulting organic phases; and    (c′4) removal of the organic solvent.    
     
     
         7 . The process according to  claim 1 , wherein the hydrolysis in (d′) is effected by means of a mixture of sodium hydroxide solution or potassium hydroxide solution and triethanolamine.  
     
     
         8 . The process according to  claim 1 , wherein diastereomeric secondary amines or amides are used and the stereochemical purity of the resulting products is not significantly changed by the oxidation.  
     
     
         9 . A method of regioselective oxidation comprising oxidating secondary bisbenzylamines or bisbenzylamides having at least one benzylic hydrogen atom.  
     
     
         10 . A process for the regioselective cleavage of secondary amines or amides, which comprises the following process steps: 
 (a″) provision of at least one secondary bisbenzylamine or bisbenzylamide having at least one benzylic hydrogen atom in a solvent, with the solvent optionally comprising a nucleophile;    (b″) oxidation of the secondary amine or amide by means of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), giving an oxidation product mixture;    (c″) reaction of the oxidation product mixture with a nucleophile.    
     
     
         11 . The process according to  claim 10 , wherein at least one benzyl ring of the bisbenzylamines or bisbenzylamides is substituted by an electron-pushing substituent which exerts a +I effect and/or a +M effect on the benzyl ring.  
     
     
         12 . The process according to  claim 11 , wherein a nucleophilic solvent selected from the group consisting of methanol, ethanol, n-propanol, i-propanol and butanol is used in process step (a).  
     
     
         13 . The process according to  claim 11 , wherein the electrochemical oxidation is carried out under at least one of the following conditions: 
 a temperature of from −20 to 60° C.;    a current density of from 1 to 1000 mA/cm 2 ;    a concentration of the electrolyte salt of from 0.0001 to 5 mol/l.    
     
     
         14 . The process according to  claim 12 , wherein the electrochemical oxidation is carried out under at least one of the following conditions: 
 a temperature of from −20 to 60° C.;    a current density of from 1 to 1000 mA/cm 2 ;    a concentration of the electrolyte salt of from 0.0001 to 5 mol/l.    
     
     
         15 . The process according to  claim 11 , wherein the electrolysis solution is worked up as follows in process step (c′): 
 (c′1) removal of the solvent and addition of water, an organic solvent selected from the group consisting of dichloromethane, chloroform, ethers, esters and hydrocarbons, and an acid;    (c′2) extraction of the mixture resulting from process step (c′1) with an organic solvent selected from the group consisting of dichloromethane, chloroform, ethers, esters and hydrocarbons;    (c′3) drying of the resulting organic phases;    (c′4) removal of the organic solvent.    
     
     
         16 . The process according to  claim 12 , wherein the electrolysis solution is worked up as follows in process step (c′): 
 (c′1) removal of the solvent and addition of water, an organic solvent selected from the group consisting of dichloromethane, chloroform, ethers, esters and hydrocarbons, and an acid;    (c′2) extraction of the mixture resulting from process step (c′1) with an organic solvent selected from the group consisting of dichloromethane, chloroform, ethers, esters and hydrocarbons;    (c′3) drying of the resulting organic phases;    (c′4) removal of the organic solvent.    
     
     
         17 . The process according to  claim 13 , wherein the electrolysis solution is worked up as follows in process step (c′): 
 (c′1) removal of the solvent and addition of water, an organic solvent selected from the group consisting of dichloromethane, chloroform, ethers, esters and hydrocarbons, and an acid;    (c′2) extraction of the mixture resulting from process step (c′1) with an organic solvent selected from the group consisting of dichloromethane, chloroform, ethers, esters and hydrocarbons;    (c′3) drying of the resulting organic phases;    (c′4) removal of the organic solvent.    
     
     
         18 . The process according to  claim 1   1 , wherein the hydrolysis in process step (d′) is effected by means of a mixture of sodium hydroxide solution or potassium hydroxide solution and triethanolamine.  
     
     
         19 . The process according to  claim 12 , wherein the hydrolysis in process step (d′) is effected by means of a mixture of sodium hydroxide solution or potassium hydroxide solution and triethanolamine.  
     
     
         20 . The process according to  claim 13 , wherein the hydrolysis in process step (d′) is effected by means of a mixture of sodium hydroxide solution or potassium hydroxide solution and triethanolamine.