Keeping Your Students Awake: Facile Microscale Synthesis of Modafinil, a Modern Anti-Narcoleptic Drug

This article describes the microscale preparation of modafinil, a pharmaceutical recently approved for the treatment of narcolepsy, by a sulfide oxidation reaction. The synthesis is straightforward and appropriate as part of a midlevel undergraduate organic laboratory. An unusual feature of modafinil is the presence of a chiral sulfoxide functionality where a sulfur atom acts as a stereocenter. This apprises students that atoms other than carbon can act as centers of chirality. The diastereotopic nature of protons adjacent to the sulfur stereocenter can be identified by 1H NMR spectroscopy, and functional group changes monitored by IR spectroscopy. The nature of modafinil and its role in society as an anti-narcoleptic is a source of attraction and fascination among undergraduates.