Process for Preparing Chiral 3-Triazolyl Sulphoxide Derivatives

Abstract

The present invention relates to a catalytic process for preparing 3-triazolyl sulphoxide derivatives in enantiomerically pure or enantiomerically enriched form.

1 . Process for preparing 3-triazolyl sulphoxide derivatives of the formula (I) in an enantiomerically pure or enantiomerically enriched form 
       
         
           
           
               
               
           
         
       
       in which
 X 1  and X 2  are each independently fluorine, chlorine, bromine, hydrogen, (C 1 -C 12 )alkyl, (C 1 -C 12 )haloalkyl, 
 Y 1  and Y 2  are each independently fluorine, chlorine, bromine, hydrogen, (C 1 -C 12 )alkyl, (C 1 -C 12 )haloalkyl, 
 R 1  and R 2  are each independently hydrogen, (C 1 -C 12 )alkyl, (C 1 -C 12 )haloalkyl, cyano, halogen, nitro, 
 R 3  is hydrogen, (C 1 -C 12 )alkyl, amino, nitro, NH(CO)(C 1 -C 12 )alkyl, N═CR′R 
 where R, R′ are each independently hydrogen, (C 1 -C 12 )alkyl, aryl, 
 
       characterized in that
 (A) a sulphide of the formula (II) 
 
       
         
           
           
               
               
           
         
       
       in which X 1 , X 2 , Y 1 , Y 2 , R 1 , R 2  and R 3  are each as defined above 
       is converted in the presence of a chiral catalyst and of an oxidizing agent. 
     
     
         2 . Process according to  claim 1 , characterized in that the enantiomer ratio is 50.5:49.5 to 99.5:0.5 (+):(−) or (−):(+)-enantiomer. 
     
     
         3 . Process according to either of  claims 1  and  2 , characterized in that the enantiomer ratio is 50.5:49.5 to 99.5:0.5 (+):(−) enantiomer. 
     
     
         4 . Process according to any of  claims 1  to  3 , characterized in that
 X 1  and X 2 , Y 1  and Y 2  are each independently fluorine, chlorine, hydrogen, (C 1 -C 12 )haloalkyl, 
 R 1  and R 2  are each independently fluorine, hydrogen, (C 1 -C 6 )alkyl, 
 R 3  is hydrogen, amino. 
 
     
     
         5 . Process according to any of  claims 1  to  4 , characterized in that
 X 1  and X 2 , Y 1  and Y 2  are each independently fluorine, hydrogen, (C 1 -C 6 )haloalkyl, 
 R 1  and R 2  are each independently fluorine, methyl, 
 R 3  is hydrogen. 
 
     
     
         6 . Process according to any of  claims 1  to  5 , characterized in that the oxidizing agents used are organic or inorganic peroxides. 
     
     
         7 . Process according to any of  claims 1  to  6 , characterized in that the chiral catalyst used is a chiral metal-ligand complex, where the metal is a transition metal and the ligand is a compound of the formula (III) or (IV) 
       
         
           
           
               
               
           
         
       
       where, in formula (III),
 R 4  and R 5  are each independently hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylphenyl, phenyl, halogen, cyano, nitro, cyano(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, 
 R 6  is (C 1 -C 6 )alkyl, halogen-, cyano-, nitro-, amino-, hydroxyl- or phenyl-substituted (C 1 -C 6 )alkyl, carboxyl, carbonyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, di(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, 
 R 7  is hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylphenyl, aryl, aryl(C 1 -C 6 )alkyl, preferably tert-butyl, benzyl, phenyl, 
 and chiral carbon atoms are designated *, 
 
       where, in formula (IV),
 R 8  is hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylphenyl, phenyl, halogen, cyano, nitro, cyano(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, 
 R 9  and R 10  are each hydrogen, (C 1 -C 6 )alkyl, phenyl, where R 9  and R 10  may form a bridge, and 
 chiral carbon atoms are designated *. 
 
     
     
         8 . Process according to any of  claims 1  to  7 , characterized in that step (A) is followed by performing a crystallization from organic solvent or a mixture of organic solvent with water. 
     
     
         9 . Enantiomerically pure or enantiomerically enriched 3-triazolyl sulphoxide derivatives of the formula (I), preparable by the process according to any of  claims 1  to  8 , where the enantiomer ratio is 50.5:49.5 to 99.5:0.5 (+):(−)enantiomer.