PROTON AFFINITIES AND PREFERRED PROTONATION SITES IN 3-SUBSTITUTED AND 4-SUBSTITUTED PYRIDINES - PREDICTION FROM 1S ORBITAL ENERGIES

We have carried out an ab initio study of 21 3-and 4-substituted pyridine derivatives, using a ST0-3G minimal basis set. The linear correlation found between N1s orbital energies and experimental PA for these compounds is different from the one obtained for anilines, indicating that relaxation energy is sensitive to details of local bonding at the nitrogen atom. There exists a linear correlation between the n orbital energies, if this orbital is centered on the ring nitrogen, and experimental PA. A similar correlation exists for the minimum value of the molecular electrostatic potential. No correlation was found between PA values and the net charge at the ring nitrogen. Cyanopyridines are predicted to undergo protonation on the ring nitrogen. 4-Nitropyridine can protonate either on the ring nitrogen or on the oxygen atoms. The lactam form of 4-hydroxypyridine is a much stronger base than the lactim one. © 1979, American Chemical Society. All rights reserved.