Synthesis and Determination of the p K a Values of a Series of Bis(anilino)furazano[ 3, 4‐b ]pyrazines

Mitochondrial uncouplers such as bis(anilino)furazano[ 3,   4‐b ]pyrazines are potentially useful as metabolic probes and as pharmaceutical treatments for obesity. The ongoing development of such molecules would be facilitated by an ability to predict and control the p K a value of the dissociable proton(s). In this work, new analogues based on the aforementioned scaffold were prepared utilising a novel method for incorporating the aniline substituents. The p K a values of these species were measured using a bracketing indicator method. The p K a values correlated well with, and showed a strong dependence on, the electronic nature of the substituent (including for those at the ortho position). The second deprotonation of these species was also evaluated, with a similar trend noted.