Catalytic titanium (IV) oxide, mediated geminal symmetric dialkylation of carboxamides

Abstract

The present invention relates to a process preparing compounds of the general formula (I) wherein R 1 , R 2 , R 3 and R 4 are defined herein.

1 . A process for preparing compounds of the general formula (I)  
       
         
           
           
               
               
           
         
       
       in which 
 R 1 , R 2  and R 3  independently of one another are H, A, Ar, —Si(R 6 ) 3 , —Sn(R 6 ) 3 , —SR 7 , —OR 7 , —NR 8 R 9  or R 1  and R 2  or R 1  and R 3  or R 8  and R 9  can be attached to one another and together form a cyclic ring having 3 to 8 C atoms which optionally contains, in addition to nitrogen, at least one further heteroatom selected from the group consisting of —S—, —O— and —NR 6 —,  
 R 4  is A, Ar, —Si(R 6 ) 3 , —Sn(R 6 ) 3 , —SR 7 , —OR 7 , —NR 8 R 9  in which R 8  and R 9  are as defined above or R 8  and R 9  or two radicals R 4  can be attached to one another and together form a cyclic ring having 3 C atoms, R 6 , R 7 , R 8  and R 9  independently of one another are A or Ar,  
 A is a straight-chain or branched alkyl radical having from 1 to 10 C atoms, a straight-chain or branched alkenyl radical having 2 to 10 C atoms, or a straight-chain or branched alkynyl radical having 2-10 C atoms or a substituted or unsubstituted cycloalkyl radical having 3-8 C atoms, or a mono- or polyunsaturated cycloalkyl radical having 3-8 C atoms, and  
 Ar is a substituted or unsubstituted aryl radical having 6-20 C atoms, characterized in that a compound of the general formula (II)  
                     
 in which  
 R 1 , R 2  and R 3  have the meanings given above for the formula (I) is reacted with a reagent of the general formula (IIIa) or a nucleophilic reagent of the general formula (IIIb) 
 Z-R 4   (IIIa)Z-R 4 —R 4 -Z  (IIIb) 
 in which  
 R 4  has the meaning given for the formula (I), and  
 Z is Li or MgX where  
 X is Hal and  
 Hal is Cl, Br or I, which is/are generated in situ or added directly, and the process is carried out in the presence of catalytic amounts of a metal dioxide selected from the group consisting of titanium dioxide, zirconium dioxide and hafnium dioxide.  
 
     
     
         2 . A process according to  claim 1 , characterized in that it is carried out in the presence of a cocatalyst.  
     
     
         3 . A process according to  claim 1 , characterized in that it is carried out in the presence of a metal isopropoxide or an alkylsilyl halide cocatalyst.  
     
     
         4 . A process according to  claim 2 , characterized in that the cocatalyst used is a metal isopropoxide of the general formula (IV) or an alkylsilyl halide of the general formula (V) 
       M′ (s+)  (O-isopropyl) s   (IV)R 3 SiX  (V) 
       in which 
 M′ is Al, Ca, Na, K, Si or Mg,  
 s is an integer from 1 to 4 and is the oxidation state of the metal,  
 R is alkyl having 1 to 10 C atoms or aryl having 6 to 20 C atoms,  
 X is F, Cl, Br, or CN.  
 
     
     
         5 . A process according to  claim 1 , characterized in that the catalyst used is titanium dioxide.  
     
     
         6 . A process according to  claim 1 , characterized in that 
 a) a carboxamide of the general formula (II), 1-15 mol %, based on the carboxamide, of a metal dioxide selected from the group consisting of titanium dioxide, zirconium dioxide and hafnium dioxide and, if appropriate, the cocatalyst are initially charged at 10-30° C. under an atmosphere of inert gas in a solvent selected from the group consisting of toluene, THF, n-hexane, benzene and diethyl ether,    b) a solution comprising a nucleophilic reagent of the general formula (IIIa) or (IIIb)    in which    R 4  is A, Ar, —Si(R 6 ) 3 , —Sn(R 6 ) 3 , —SR 7 , —OR 7 , —NR 8 R 9  in which R 8  and R 9  are as defined above or R 8  and R 9  or two radicals R 4  can be attached to one another and together form a cyclic ring having 3 C atoms,    R 6 , R 7 , R 8  and R 9  independently of one another are A or Ar,    A is a straight-chain or branched alkyl radical having from 1 to 10 C atoms, a straight-chain or branched alkenyl radical having 2 to 10 C atoms, or a straight-chain or branched alkynyl radical having 2-10 C atoms or a substituted or unsubstituted cycloalkyl radical having 3-8 C atoms, or a mono- or polyunsaturated cycloalkyl radical having 3-8 C atoms, and    Ar is a substituted or unsubstituted aryl radical having 6-20 C atoms,    Z is Li or MgX where    X is Hal and    Hal is Cl, Br or I,    is added dropwise and    c) the mixture is allowed to react with stirring and, after the reaction has ended, worked up in a customary manner,    or in that, if Z=MgX,    a′) magnesium turnings, a carboxamide of the general formula (II), 1-15 mol %, based on the carboxamide, of a metal dioxide selected from the group consisting of titanium dioxide, zirconium dioxide and hafnium dioxide and, if appropriate, the cocatalyst are initially charged at 10-30° C. under an atmosphere of inert gas in a solvent selected from the group consisting of toluene, THF, n-hexane, benzene and diethyl ether,    b′) an alkyl halide, dissolved in a solvent selected from the group consisting of toluene, THF, n-hexane, benzene and diethyl ether, and of the general formula (IIIa′) of (IIIb′)   X—R 4   (IIIa′)orX—R 4 —R 4 —X  (IIIb′)   in which    R 4  is A, Ar, —Si(R 6 ) 3 , —Sn(R 6 ) 3 , —SR 7 , —OR 7 , —NR 8 R 9  in which R 8  and R 9  are as defined above or R 8  and R 9  or two radicals R 4  can be attached to one another and together form a cyclic ring having 3 C atoms,    R 6 , R 7 , R 8  and R 9  independently of one another are A or Ar,    A is a straight-chain or branched alkyl radical having from 1 to 10 C atoms, a straight-chain or branched alkenyl radical having 2 to 10 C atoms, or a straight-chain or branched alkynyl radical having 2-10 C atoms or a substituted or unsubstituted cycloalkyl radical having 3-8 C atoms, or a mono- or polyunsaturated cycloalkyl radical having 3-8 C atoms, and    Ar is a substituted or unsubstituted aryl radical having 6-20 C atoms,    X is Cl, Br, or I;    is added dropwise,    c′) the mixture is allowed to react with stirring and, after the reaction had ended, worked up in a customary manner.    
     
     
         7 . A process according to  claim 6 , characterized in that the process step a) or a′) is carried out at a temperature of 15-25° C.  
     
     
         8 . A process according to  claim 6 , characterized in that the process step a) or a′) is carried out at room temperature.  
     
     
         9 . A process according to  claim 1 , characterized in that the nucleophilic reagent used is a lithium compound of the general formula (IIIa) or (IIIb) in which R 4  is A, Ar, —Si(R 6 ) 3 , —Sn(R 6 ) 3 , —SR 7 , —OR 7 , —NR 8 R 9  in which R 8  and R 9  are as defined above or R 8  and R 9  or two radicals R 4  can be attached to one another and together form a cyclic ring having 3 C atoms, 
 R 6 , R 7 , R 8  and R 9  independently of one another are A or Ar,  
 A is a straight-chain or branched alkyl radical having from 1 to 10 C atoms, a straight-chain or branched alkenyl radical having 2 to 10 C atoms, or a straight-chain or branched alkynyl radical having 2-10 C atoms or a substituted or unsubstituted cycloalkyl radical having 3-8 C atoms, or a mono- or polyunsaturated cycloalkyl radical having 3-8 C atoms, and  
 Ar is a substituted or unsubstituted aryl radical having 6-20 C atoms.  
 
     
     
         10 . A process according  claim 1 , characterized in that the compound that the nucleophilic reagent used is a compound of the general formula (IIIa) or (IIIb) in which R 4  is methyl, ethyl, n- or isopropyl, iso-, sec- or tert-butyl, n-hexyl, cyclopentyl, cyclohexyl, allyl, vinyl, phenyl or benzyl.  
     
     
         11 . A process according to  claim 1 , characterized in that the compound that is reacted is a compound of the general formula (II) in which R 1 , R 2  and R 3  independently of one another are H, methyl, ethyl, n- or isopropyl, iso-, sec- or tert-butyl, n-hexyl, phenyl or benzyl.  
     
     
         12 . A process for preparing compounds of the general formula (I)  
       
         
           
           
               
               
           
         
       
       in which 
 R 1 , R 2  and R 3  independently of one another are H, A, Ar, —Si(R 6 ) 3 , —Sn(R 6 ) 3 , —SR 7 , —OR 7 , —NR 8 R 9  or R 1  and R 2  or R 1  and R 3  or R 8  and R 9  can be attached to one another and together form a cyclic ring having 3 to 8 C atoms which optionally contains, in addition to nitrogen, at least one further heteroatom selected from the group consisting of —S—, —O— and —NR 6 —,  
 R 4  is A, Ar, —Si(R 6 ) 3 , —Sn(R 6 ) 3 , —SR 7 , —OR 7 , —NR 8 R 9  in which R 8  and R 9  are as defined above or R 8  and R 9  or two radicals R 4  can be attached to one another and together form a cyclic ring having 3 C atoms  
 R 6 , R 7 , R 8  and R 9  independently of one another are A or Ar,  
 A is a straight-chain or branched alkyl radical having from 1 to 10 C atoms, a straight-chain or branched alkenyl radical having 2 to 10 C atoms, or a straight-chain or branched alkynyl radical having 2-10 C atoms or a substituted or unsubstituted cycloalkyl radical having 3-8 C atoms, or a mono- or polyunsaturated cycloalkyl radical having 3-8 C atoms, by carrying out the process in the presence of a catalyst system, comprising a metal dioxide selected from the group consisting of titanium dioxide, and hafnium dioxide and a cocatalyst of the general formula (IV), (V) 
 M′ (s+)  (O-isopropyl) s   (IV)R 3 SiX  (V) 
 in which  
 M′ is Al, Ca, Na, K, Si or Mg,  
 s is an integer from 1 to 4 and is the oxidation state of the metal,  
 R is alkyl having 1 to 10 C atoms or aryl having 6 to 20 C atoms,  
 X is F, Cl, Br, or CN,  
 or the general formulae  
 (CH 3 ) 2 ClSi(CH 2 ) 2 SiCl(CH 3 ) 2    
 (CH 3 ) 2 ClSi(CH 2 ) 3 CN  
 [(CH 3 ) 3 Si] 2 O  
 [(CH 3 ) 3 Si] 2 NH or  
 [(CH 3 ) 3 Si] 2 .  
 
     
     
         13 . A process according to  claim 4 , wherein M 1  is Mg or Na.  
     
     
         14 . A process according to  claim 12 , wherein M 1  is Mg or Na.