The proton affinities of saturated and unsaturated heterocyclic molecules

The proton affinities derived from G3-calculations of 23 five-membered ring heteroaromatic molecules agree well with the experimentally determined values available in the literature. The calculated local proton affinities show that the principal site of protonation of the heteroaromatic compounds examined is an atom of the ring, carbon when there is only one heteroatom in the ring, and nitrogen where there are two or more heteroatoms. The experimental proton affinities of non-aromatic cyclic ethers, amines and thioethers are also in excellent agreement with the calculated values, with two exceptions (oxetane, N-methylazetidine). The literature proton affinities of the four simple cyclic ethers, oxetane, tetrahydrofuran, tetrahydropyran and oxepane were confirmed by Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry, in order to examine the disagreement between the values predicted by extrapolation or additivity for tetrahydrofuran and tetrahydropyran and those determined by experiment and by calculation. The proton affinity differences between the pairs tetrahydropyran/1,4-dioxane, piperidine/morpholine and related compounds show that introduction of an additional oxygen atom in the ring considerably lowers the basicity.