Asymmetric synthesis of modafinil via induction of chirality with cyclohexane-1,2-bis(arylmethyleneamine) ligands

Diphenyl methyl sulfinyl acetamid (Modafinil) is used clinically in the treatment of narcolepsy and sleeping disorders. The synthesis of R-modafinil, begins with the reaction of benzhydrol and thioglycolic acid in trifluoroacetic acid to afford benzhydrylsulfanylacetic acid. The reaction of acid with thionyl chloride in benzene followed by treatment with ammonium hydroxide gave acetamide. Synthesis of novel chiral catalyst by a simple and efficient method has been reported. The process occurs at room temperature in toluene as a solvent and in the presence of a bidendate bis(imine)–titanium isopropoxide complex as catalyst. The obtained catalysts were characterized with FT-IR, 1H NMR, 13C NMR, and mass spectral and used for the first time in oxidation of 2-(benzhydrylthio)acetamid. The reaction using this catalysts exhibits very good yield and appropriate enantioselectivity.

Keywords:

diphenyl methyl sulfinyl acetamid , modafinil , cyclohexane-1 , 2-bis(arylmethyleneamine) ligands