Broad Survey of Selectivity in the Heterogeneous Hydrogenation of Heterocycles

A broad survey of heterogeneous hydrogenation catalysts has been conducted for the reduction of heterocycles commonly found in pharmaceuticals. The comparative reactivity of these substrates is reported as a function of catalyst, temperature, and hydrogen pressure. This analysis provided several catalysts with complementary reactivity between substrates. We then explored a series of bisheterocyclic substrates that provided an intramolecular competition of heterocycle hydrogenation reactivity. In several cases, complete selectivity could be achieved for reduction of one heterocycle and isolated yields are reported. A general trend in reactivity is inferred in which quinoline is the most reactive, followed by pyrazine, then pyrrole and with pyridine being the least reactive.