Process for the preparation of tetrazole derivatives from organo boron and organo aluminium azides

Abstract

The present invention relates to a method for preparing substituted tetrazoles, compounds obtained according to this method, new reactants and new tetrazole derivatives.

1 . A process for the manufacture of a tetrazole of formula 
       
         
           
           
               
               
           
         
         or a tautomer or a salt thereof, wherein R represents an organic residue; 
         comprising 
         (i) reacting a compound of formula R—CN (II a) with an azide of formula, (R 1 )(R 2 )M-N 3  (IIb), wherein R has the meaning as defined above; R 1  and R 2 , independently of another, represent an organic residue such as an aliphatic residue, an alicyclic residue, a heteroalicyclic residue; an alicyclic-aliphatic residue; a heteroalicyclic-aliphatic residue; a carbocyclic or a heterocyclic aromatic residue; an araliphatic residue or an heteroaraliphatic residue, each residue, independently of another, being unsubstituted or substituted; and M is boron or aluminium; and 
         (ii) isolating the resulting compound of formula (I). 
       
     
     
         2 . A process according to  claim 1  for the manufacture of a compound of formula (IV b) comprising reacting a compound of formula (IV c) 
       
         
           
           
               
               
           
         
         or an ester thereof with an azide of formula (R 1 )(R 2 )M-N 3  (Ilb), wherein R 1  and R 2 , independently of each other, have the meanings as defined above, and isolating the compound of formula (IV b). 
       
     
     
         3 . A process according to  claim 1  for the manufacture of a compound of formula manufacture of a compound of formula 
       
         
           
           
               
               
           
         
         a tautomeric form thereof wherein Ry represents C 1 -C 8 -alkyl such as methyl; C 1 -C 8 -alkyl substituted by X′ and X′ being halogen, sulphonyloxy, hydroxyl, protected hydroxyl, such as bromomethyl, or an acetal of formyl; and X 1  being in a benzylic position, comprising reacting a compound of formula (IV a) 
       
       
         
           
           
               
               
           
         
         with a compound of formula (R 1 )(R 2 )M-N 3  (II b), wherein R 1  and R 2 , independently of one another, represent an organic residue; and isolating the resulting compound of formula (V). 
       
     
     
         4 . A process for the manufacture of the compound of formula (VI) 
       
         
           
           
               
               
           
         
         or a tautomer or salt thereof, comprising 
         (a) treating a compound of formula (VI a), 
       
       
         
           
           
               
               
           
         
         wherein X represents a leaving group, first with a nucleophilic agent and then with a “solvolytic” base resulting in a compound of formula (VI b) 
       
       
         
           
           
               
               
           
         
         (b) reacting a compound of formula (V b) with an azide of formula (R 1 )(R 2 )M-N 3  (II b), wherein the variables R 1  and R 2 , independently of one another, have the meanings as defined above: resulting in a compound of formula (VI c) 
       
       
         
           
           
               
               
           
         
       
       or a tautomer or salt thereof
 (c) oxidizing a compound of formula (VI c) or a tautomer or salt thereof resulting in a compound of formula (VI) 
 
       
         
           
           
               
               
           
         
         or a tautomer or salt thereof; and 
         (d) isolating the compound of formula (VI) or a tautomer or salt thereof. 
       
     
     
         5 . A process for the manufacture of a compound of formula (V d) 
       
         
           
           
               
               
           
         
         comprising oxidizing a compound of formula (VI c) 
       
       
         
           
           
               
               
           
         
         or a tautomer or salt thereof resulting in a compound of formula (VI) or a tautomer or salt thereof; and isolating a resulting compound of formula (VI). 
       
     
     
         6 . A process according to  claim 4 , wherein the oxidation is carried out in the presence of an oxidation agent selected from the group consisting of HNO 2 , HNO 3  or a corresponding anhydride thereof, and a peroxodisulfate, and wherein as solvent an alkylated aromatic hydrocarbon solvent such as toluene is used. 
     
     
         7 . A process according to  claim 1  for the manufacture of a compound of formula 
       
         
           
           
               
               
           
         
         a tautomeric form thereof, wherein Ry represents C 1 -C 8 -alkyl such as methyl; C 1 -C 8 -alkyl substituted by X′ and X′ being halogen, sulphonyloxy, hydroxyl, protected hydroxyl, such as bromomethyl, formyl or an acetal thereof; comprising reacting a compound of formula (VII a) 
       
       
         
           
           
               
               
           
         
         with a compound of formula (R 1 )(R 2 )M-N 3  (II b), wherein R 1  and R 2 , independently of one another, represent an organic residue; and isolating the resulting compound of formula (VI). 
       
     
     
         8 . A process according to  claim 1 , wherein a compound of formula (R 1 )(R 2 )M-N 3  (II b) is used, wherein M is aluminium or boron; and R 1  and R 2 , independently of one another, is C 1 -C 8 -alkyl such as methyl, ethyl, propyl, diisobutyl, tert-butyl or n-octyl; C 3 -C 7 alkenyl such as allyl or crotyl, C 3 -C 7 -cycloalkyl such as cyclohexyl; phenyl-C 1 -C 4 -alkyl such as benzyl or 2-phenethyl; phenyl-C 3 -C 5 alkenyl such as cinnamyl, or C 3 -C 8 -cycloalkyl-C 1 -C 8 -alkyl such as cyclopropylmethyl or cyclohexylmethyl. 
     
     
         9 . A compound of formula (R 1 )(R 2 )M-N 3  (II b), wherein M is aluminium or boron; and R 1  and R 2 , independently of one another, is C 3 -C 7 alkenyl such as allyl or crotyl, C 3 -C 7 -cycloalkyl such as cyclohexyl; phenyl-C 1 -C 4 -alkyl such as benzyl or 2-phenethyl; phenyl-C 3 -C 5 alkenyl such as cinnamyl, or C 3 -C 8 -cycloalkyl-C 1 -C 8 -alkyl such as cyclopropylmethyl or cyclohexylmethyl. 
     
     
         10 . A process according to  claim 5 , wherein the oxidation is carried out in the presence of an oxidation agent selected from ghe group consisting of HNO2, HNO2 or a corresponding anhydride thereof, and a peroxodisulfate, and wherein as solvent an alkylated aromatic hydrocarbon solvent such as toluene is used. 
     
     
         11 . A process according to  claim 1 , wherein a compound of formula (R 1 )(R 2 )M-N 3  (II b) is used, wherein M is aluminium or boron; and R 1  and R 2 , independently of one another, is C 1 -C 8 -alkyl such as methyl, ethyl, propyl, diisobutyl, tert-butyl or n-octyl; C 3 -C 7 alkenyl such as allyl or crotyl, C 3 -C 7 -cycloalkyl such as cyclohexyl; phenyl-C 1 -C 4 -alkyl such as benzyl or 2-phenethyl; phenyl-C 3 -C 5 alkenyl such as cinnamyl, or C 3 -C 8 -cycloalkyl-C 1 -C 8 -alkyl such as cyclopropylmethyl or cyclohexylmethyl. 
     
     
         12 . A process according to  claim 3 , wherein a compound of formula (R 1 )(R 2 )M-N 3 (II b) is used, wherein M is aluminium or boron; and R 1  and R 2 , independently of one another, is C 1 -C 8 -alkyl such as methyl, ethyl, propyl, diisobutyl, tert-butyl or n-octyl; C 3 -C 7 alkenyl such as allyl or crotyl, C 3 -C 7 -cycloalkyl such as cyclohexyl; phenyl-C 1 -C 4 -alkyl such as benzyl or 2-phenethyl; phenyl-C 3 -C 5 alkenyl such as cinnamyl, or C 3 -C 8 -cycloalkyl-C 1 -C 8 -alkyl such as cyclopropylmethyl or cyclohexylmethyl. 
     
     
         13 . A process according to any one of  claim 4 , wherein a compound of formula (R 1 )(R 2 )M-N 3  (II b) is used, wherein M is aluminium or boron; and R 1  and R 2 , independently of one another, is C 1 -C 8 -alkyl such as methyl, ethyl, propyl, diisobutyl, tert-butyl or n-octyl; C 3 -C 7 alkenyl such as allyl or crotyl, C 3 -C 7 cycloalkyl such as cyclohexyl; phenyl-C 1 -C 4 -alkyl such as benzyl or 2-phenethyl; phenyl-C 3 -C 5 alkenyl such as cinnamyl, or C 3 -C 8 -cycloalkyl-C 1 -C 8 -alkyl such as cyclopropylmethyl or cyclohexylmethyl. 
     
     
         14 . A process according to  claim 7 , wherein a compound of formula (R 1 )(R 2 )M-N 3  (II b) is used, wherein M is aluminium or boron; and R 1  and R 2 , independently of one another, is C 1 -C 8 -alkyl such as methyl, ethyl, propyl, diisobutyl, tert-butyl or n-octyl; C 3 -C 7 alkenyl such as allyl or crotyl, C 3 -C 7 cycloalkyl such as cyclohexyl; phenyl-C 1 -C 4 -alkyl such as benzyl or 2-phenethyl; phenyl-C 3 -C 8 alkenyl such as cinnamyl, or C 3 -C 8 -cycloalkyl-C 1 -C 8 -alkyl such as cyclopropylmethyl or cyclohexylmethyl.