Formamidine Ureas as Tunable Electrophiles

Formamidine urea compounds exchange imine fragments with primary nitrogen nucleophiles, allowing the preparation of a variety of derivatives from a single precursor. The reactivities of these species are governed primarily by the electron‐donating power of the substituents and are tunable over a range of >103 in first‐order rates of hydrolysis. Formamidine ureas such as 1, available in large amounts and pictured here, undergo facile exchange reactions with primary nitrogen centers of amines, hydrazines, hydrazides, and hydroxylamines. The resulting compounds differ in their susceptibility to hydrolysis by more than three orders of magnitude in rate constant, due primarily to electronic effects of the amine substituents. These factors make formamidine ureas an accessible and attractive class of potential pharmacophores.