Synthesis of Cyanamides via a One-Pot Oxidation–Cyanation of Primary and Secondary Amines

An operationally simple oxidation–cyanation method for the synthesis of cyanamides is described. The procedure utilizes inexpensive and commercially available N-chlorosuccinimide and Zn­(CN)₂ as reagents to avoid direct handling of toxic cyanogen halides. It is demonstrated to be amenable for the cyanation of a variety of primary and secondary amines and aniline derivatives as well as a complex synthetic intermediate en route to verubecestat (MK-8931). Additionally, kinetic measurements and other control experiments are reported to shed light onto the mechanism of this cyanation reaction.