What are the pKa values of C–H bonds in aromatic heterocyclic compounds in DMSO?

A first-principle method has been successfully developed for the prediction of pKa values of aromatic heterocyclic compounds in DMSO solution with a precision of 1.1 pKa units. Comparison of theoretical results and experimental data (where available) also shows excellent consistency. Armed with this useful approach, the pKa values for a series of aromatic heterocycles were calculated in DMSO. Moreover, a discussion of the relationships between hydrogen acidities and molecular structures is conducted for the first time (determinants of C–H acidities, substituent effects, and some practical use of dehydrometalation). These statistics could be useful for synthetic chemists to design proper routes for introduction of aromatic heterocyclic moiety, especially when dehydrometalation reactions are used.