Synthesis procedure for biphenylimidazolyl-(1)-phenylmethane and related compounds

Abstract

Synthesis of Bifonazole by reducing 4-phenylbenzophenone to the alcohol and reacting the alcohol in solid phase under microwave irradiation with imidazole.

1. A synthesis procedure for the manufacture of biphenylimidazolyl-(1)-phenylmethane, comprising the reduction of 4-phenyl-benzophenone and subsequent reaction of biphenyl-phenyl-carbinol with imidazole. 
     
     
       2. A synthesis procedure according to  claim 1 , where the reduction of 4-phenyl-benzophenone is carried out with sodium borohydride in the presence of alumina. 
     
     
       3. A synthesis procedure according to  claim 1    claim 2 , where the molar ratio between 4-phenyl-benzophenone and sodium borohydride is  1 : 0 . 5    1 - 0 . 05  moles of the  4 -phenyl-benzophenone to 1.0 mole sodium borohydride ( 1 : 0 . 5 - 1 ) . 
     
     
       4. A synthesis procedure according to  claim 1    claim 2 , where the ratio in mass between alumina and 4-phenyl-benzophenone is  0 . 01 : 25 - 1    0 . 01 - 25 : 1 . 
     
     
       5. A synthesis procedure according to  claim 1 , where a protic solvent is used, for example ethanol . 
     
     
       6. A synthesis procedure according to  claim 1    claim 5 , where the protic solvent used is in a mass ratio with 4-phenyl-benzophenone of  1 : 2 - 1    1 - 2 : 1 . 
     
     
       7. A synthesis procedure according to  claim 1    claim 2 , wherein ethanol is used as a protic solvent in the synthesis procedure and where the time of reaction between sodium borohydride and 4-phenyl-benzophenone in the presence of alumina and ethanol is from 10 to 60 minutes. 
     
     
       8. A synthesis procedure according to  claim 7 , where no heating is necessary besides the exothermal effect produced by the reaction itself. 
     
     
       9. A synthesis procedure according to  claim 8 , where the conversion of 4-phenyl-benzophenone into biphenyl-phenyl-carbinol is 90-99%. 
     
     
       10. The synthesis procedure according to  claim 1 , where the biphenyl-phenyl-carbinol reacts in a further step of synthesis with imidazole, in a molar ratio of biphenyl-phenyl-carbinol to imidazole of  1 - 1 : 8    1 : 1 - 8 . 
     
     
       11. A synthesis procedure according to  claim 10 , where the reaction between biphenyl-phenyl-carbinol and imidazole is carried out in the absence of any organic or inorganic solvent. 
     
     
       12. A synthesis procedure according to  claim 11 , where the reaction between biphenyl-phenyl-carbinol and imidazole is carried out by subjecting the system to microwave irradiation. 
     
     
       13. A synthesis procedure according to  claim 12 , where the reaction time is from 3 to 40 minutes. 
     
     
       14. A synthesis procedure according to  claim 13 , where biphenylimidazolyl-(1)-phenylmethane is obtained as a reaction product in a yield of 70 to 74% of pure product. 
     
     
       15. A synthesis procedure for the manufacture of biphenylimidazolyl-(1)phenylmethane starting from 4-phenyl-benzophenone, which consists of two synthesis steps, being the first one the reduction of 4-phenyl-benzophenone to biphenyl-phenyl-carbinol with sodium borohydride in the presence of alumina, and the second step consists of the reaction between biphenyl-phenyl-carbinol and imidazole assisted by microwaves, and in the absence of every kind of organic and inorganic solvents, obtaining a yield between 70 to 74% of pure product in a total reaction time of no more than three hours, starting from 4-phenyl-benzophone. 
     
     
       16. The synthesis procedure according to  claim 5 , wherein the protic solvent is ethanol.