Enantiomers of 1-[(4-chlorophenyl) phenylmethyl]-4-[(4-methylphenyl) sulfonyl] piperazine

Abstract

Levorotatory and dextrorotatory enantiomers of 1-[(4-chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl]piperazine of the formula their preparation and use for the preparation of substantially optically pure enantiomers of 1-[(4-chlorophenyl)phenylmethyl]piperazine, which are themselves valuable intermediate products for the preparation of optically active therapeutic compounds having a very high degree of optical purity.

We claim:  
     
         1 . The levorotatory and dextrorotatory enantiomers of 1-[(4-chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl]piperazine of the formula  
       
         
           
           
               
               
           
         
       
     
     
         2 . A process for the preparation of the levorotatory and dextrorotatory enantiomers of 1-[(4-chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl]piperazine of formula I according to  claim 1 , which comprises reacting an enantiomer of (4-chlorophenyl)phenylmethylamine of the formula  
       
         
           
           
               
               
           
         
       
       with an N,N-diethyl-4-methylbenzenesulfonamide of the formula  
       
         
           
           
               
               
           
         
       
       wherein X is a chlorine, bromine or iodine atom, or the (4-methylphenyl)sulfonyloxy or methylsulfonyloxy group, in the presence 2.2 to 4.4 equivalents of an organic or inorganic base per equivalent of the enantiomer of (4-chlorophenyl)phenylmethylamine and at the boiling point of the reaction mixture.  
     
     
         3 . A process as claimed in  claim 2 , wherein the base is selected from the group consisting of ethyldiisopropylamine, N-ethylmorpholine, 2,4,6-trimethylpyridine, triethylamine and an alkali metal carbonate.  
     
     
         4 . A process as claimed in  claim 2 , wherein the base is ethyldiisopropylamine.  
     
     
         5 . A process for the preparation of the levorotatory and dextrorotatory enantiomers of 1-[(4-chlorophenyl)phenylmethyl]piperazine of the formula  
       
         
           
           
               
               
           
         
       
       which comprises subjecting an enantiomer of 1-[(4-chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl]piperazine of the formula  
       
         
           
           
               
               
           
         
       
       to hydrolysis with hydrobromic acid, in acetic acid medium, in the presence of a phenolic compound, and at a temperature of between 18 and 100° C.  
     
     
         6 . A process as claimed in  claim 5 , wherein the phenolic compound is 4-hydroxybenzoic acid.  
     
     
         7 . A process for the preparation of the levorotatory and dextrorotatory enantiomers of a 1-1(4-chlorophenyl)phenylmethyl]piperazine of the formula  
       
         
           
           
               
               
           
         
       
       wherein R is a methyl, (3-methylphenyl)methyl, (4-tert-butylphenyl)methyl, 2-(2-hydroxyethoxy)ethyl, 2-[2-[2-hydroxyethoxy)ethoxy]ethyl, 2-(carboxymethoxy)ethyl, 2-(methoxycarbonylmethoxy)ethyl or 2-(carboxymethoxy)ethyl radical, which comprises reacting an enantiomer of 1-[(4-chlorophenyl)phenylmethyl]piperazine of the formula  
       
         
           
           
               
               
           
         
       
       while hot, with a halide of the formula RX  
       wherein R has the meaning given above and X represents a halogen atom.  
     
     
         8 . A compound selected from the group consisting of 
 the levorotatory dihydrochloride of 1-[(4-chlorophenyl)phenylmethyl]-4-[(3-methylphenyl)methyl]piperazine;    the dextrorotatory dihydrochloride of 1-[(4-chlorophenyl)phenylmethyl]-4-[(3-methylphenyl)methyl]piperazine;    the levorotatory dihydrochloride of 1-[(4-tert-butylphenyl)methyl]-4-[(4 chlorophenyl)phenylmethyl]piperazine;    the dextrorotatory dihydrochloride of 1-[(4-tert-butylphenyl)methyl]-4-[(4-chlorophenyl)phenylmethyl]piperazine;    the levorotatory dihydrochloride of 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]ethanol;    the dextrorotatory dihydrochloride of 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]ethanol;    the levorotatory dibydrochloride of 2-[2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]ethoxy]ethanol;    the dextrorotatory dihydrochloride of 2-[2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]ethoxy]ethanol;    the levorotatory 2-[2-[(4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetamide and its dextrorotatory dihydrochloride;    the dextrorotatory 2-[2-[4-[(4-chlorophenyl)phenylmethyl)-1-piperazinyl]ethoxy]acetamide and its levorotatory dihydrochloride;    the levorotatory dimaleate of methyl 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetate and    the dextrorotatory dimaleate of methyl 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetate.