Pharmaceutical-Oriented Selective Synthesis of Mononitriles and Dinitriles Directly from Methyl(hetero)arenes: Access to Chiral Nitriles and Citalopram.

A pharmaceutical-oriented, transition-metal-free, cyanide-free one-step direct transformation of methylarenes to aryl nitriles is described. For the dimethylarenes, the selectivity can be well-controlled to form mononitriles or dinitriles. Enantioenriched nitriles can also be synthesized by this method. As a pharmaceutically practical method, the antidepressant drug citalopram was synthesized from cheap and commercially abundant m-xylene on a gram scale in high yield, avoiding transition-metal residues and toxic cyanides.