Method For Preparing Aryl 2-Tetrazol-1-Yl Keto With Improved Selectivity

Abstract

The present disclosure relates to a method for preparing aryl 2-tetrazol-2-yl ketone of the following Formula 1a with improved selectivity: wherein R 1 and R 2 are the same as defined herein.

1 . A method for preparing a compound of Formula 1a, comprising: 
       
         
           
           
               
               
           
         
         reacting a compound of Formula 2 with a salt of a compound of Formula 3; and 
         purifying the reaction product of the salt of the compound of Formula 3 and the compound of Formula 2, wherein the purifying step comprises a crystallizing process or a heat treatment process; 
       
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 2  are each independently selected from the group consisting of hydrogen, halogen, perfluoroalkyl having 1 to 8 carbon atoms, alkyl having 1 to 8 carbon atoms, thioalkoxy having 1 to 8 carbon atoms, and alkoxy having 1 to 8 carbon atoms; and 
         X is a leaving group. 
       
     
     
         2 - 12 . (canceled) 
     
     
         13 . A method for increasing the selectivity of synthesizing a compound of Formula 1a, comprising:
 using a salt of a compound of Formula 3 in the synthesis of a compound of Formula 1a and a compound of Formula 1b, wherein the compound of Formula 1a and the compound of Formula 1b are synthesized from reacting a compound of Formula 2 with a compound of Formula 3:   
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 2  are each independently selected from the group consisting of hydrogen, halogen, perfluoroalkyl having 1 to 8 carbon atoms, alkyl having 1 to 8 carbon atoms, thioalkoxy having 1 to 8 carbon atoms, and alkoxy having 1 to 8 carbon atoms; and 
         X is a leaving group. 
       
     
     
         14 . The method according to  claim 13 , wherein the salt of the compound of Formula 3 is obtained by reacting the compound of Formula 3 with a base. 
     
     
         15 . The method according to  claim 14 , wherein the base is an inorganic base or an organic base. 
     
     
         16 . The method according to  claim 15 , wherein the inorganic base is a metal hydroxide or a metal carbonate, and the organic base is an amine compound. 
     
     
         17 . The method according to  claim 16 , wherein the metal hydroxide is selected from lithium hydroxide, sodium hydroxide and potassium hydroxide; the metal carbonate is selected from lithium carbonate, sodium carbonate, potassium carbonate and cesium carbonate; and the amine compound is selected from triethylamine and diisopropylethylamine. 
     
     
         18 . The method according to  claim 14 , wherein the compound of Formula 3 is reacted with a base in a reaction solvent, and then the salt of the compound of Formula 3 separated from the reaction product is reacted with the compound of Formula 2. 
     
     
         19 . The method according to  claim 14 , wherein after reacting the compound of Formula 3 with a base, the compound of Formula 2 is added to the reaction product to react with the salt of the compound of chemical formula 3. 
     
     
         20 . The method according to  claim 13 , which further comprises purifying the reaction product of the salt of the compound of Formula 3 and the compound of Formula 2. 
     
     
         21 . The method according to  claim 20 , wherein the purifying step comprises a crystallizing process. 
     
     
         22 . The method according to  claim 21 , wherein the crystallizing process comprises a first crystallizing process and a second crystallizing process. 
     
     
         23 . The method according to  claim 20 , wherein the purifying step comprises a heat treatment process. 
     
     
         24 . The method according to  claim 23 , which further comprises washing with an aqueous acidic solution. 
     
     
         25 . The method according to  claim 13 , wherein R 1  and R 2  are each independently selected from the group consisting of hydrogen and halogen. 
     
     
         26 . The method according to  claim 25 , wherein R 1  and R 2  are each independently selected from the group consisting of hydrogen and chloride.