Preparation of fluorinated 1,3-benzodiozanes

Abstract

The invention relates to novel fluorinated achiral 1,3-benzodioxanes of the general formula (I-a) and (I-b) and to the preparation thereof.

1 . Compound of the general formula (I-a) or (I-b),  
     
       
         
         
             
             
         
       
     
     where 
 R 1 , R 2 , R 3 , R 4  are each independently H, CN, NO 2 , NH 2 , OH, halogen, linear or branched, optionally partly fluorinated or perfluorinated C 1 -C 4 -alkyl radicals, linear or branched, optionally partly fluorinated or perfluorinated C 1 -C 4 -alkoxy radicals, CHO, COOH, COOR, SO 2 CH 3 , SO 2 Hal, optionally substituted phenyl or pyridyl radicals, fluorocarbonyl, benzoyl, trifluoroacetyl, phenoxy, isocyanato, SO 2 F and difluorochloromethyl radicals, where R is a C 1 -C 4 -alkyl radical and Hal is a halogen radical,  
 x is H, Cl or F.  
 
   
   
       2 . Compound according to  claim 1 , characterized in that X is F.  
   
   
       3 . Compound according to  claim 1 , characterized in that R 1 , R 2 , R 3  and R 4  are each independently H, CN, NO 2 , NH 2 , Br, CH 3 , CF 3 , OCH 3 , OCF 3 , CHO, COOH, COOR or SO 2 CH 3 , where R is a C 1 -C 4 -alkyl radical.  
   
   
       4 . Compound according to  claim 1 , characterized in that at least one of the R 1 , R 2 , R 3  and R 4  radicals is different to H.  
   
   
       5 . Compound according to  claim 1 , characterized in that at least one of the R 1 , R 2 , R 3  and R 4  radicals is independently CN, NO 2 , NH 2 , Br, CHO, COOH, COOR or SO 2 CH 3 , where R is a C 1 -C 4 -alkyl radical, and all further R 1 , R 2 , R 3  and R 4  radicals are each independently H, CH 3 , OCH 3 , OCF 3  or CF 3 .  
   
   
       6 . Process for preparing a compound according to  claim 1 , characterized in that 
 d) a dihydroxy compound of the general formula (II-a)                        where    R 5 , R 6 , R 7 , R 8  are each as defined for R 1 , R 2 , R 3  and R 4  in  claim 1     is reacted with an optionally substituted dihalomethane, formaldehyde or another C 1  unit,      e) is optionally chlorinated subsequently on the methylene group, and    f) is subsequently fluorinated on the methylene group.    
   
   
       7 . Process according to  claim 6 , characterized in that the chlorination is effected under irradiation with chlorine in at least one solvent at at least one temperature of ±30° C. above and below the boiling point of this/these solvent(s).  
   
   
       8 . Process according to claims  6 , characterized in that the fluorination is effected using anhydrous HF.  
   
   
       9 . Process according to  claim 6 , characterized in that the fluorination is effected with an excess of anhydrous HF at at least one temperature of −10° C. to 20° C.  
   
   
       10 . Process according to  claim 6 , characterized in that R 5 , R 6 , R 7  and R 8  are each H.  
   
   
       11 . Process according to  claim 6 , characterized in that a substitution is subsequently carried out on the aromatic ring and/or a reaction on at least one of any substituents present on the aromatic ring.  
   
   
       12 . Process for preparing a compound according to  claim 1 , characterized in that another compound according to  claim 1  is substituted on the aromatic ring and/or a reaction is carried out on at least one of any substituents present on the aromatic ring.  
   
   
       13 . Process for preparing active pharmaceutical ingredients or medicaments comprising using a compound according to  claim 1  as intermediate or building block.