EFFECTS OF STRUCTURAL-CHANGES ON ACIDITIES AND HOMOLYTIC BOND-DISSOCIATION ENERGIES OF THE N-H BONDS IN PYRIDONES AND RELATED HETEROCYCLES

Equilibrium acidities in DMSO have been obtained for the H-N (or H-O) bonds in 2-, 3-, and 4-aminopyridines, 3-hydroxypyridine, 2- and 4-pyridones, 2-piperidone, and 2-quinolone, as well as thio analogues in which the C=O bond has been replaced by C=S. Homolytic bond dissociation energies (BDEs) for the acidic H-A bonds in these molecules have been estimated by combining the pK(HA) values with the oxidation potentials of their conjugate bases, E(ox)(A-). The acidity order for the aminopyridines was found to be 4 > 2 > 3 whereas the BDEs of their N-H bonds decreased in the opposite order, 3 > 2 > 4. The N-H bond of 2-pyridone was found to be 9.4 pK(HA) units (12.9 kcal/mol) more acidic than its saturated analogue, 2-piperidone, whereas its homolytic bond dissociation energy was found to be about 12 kcal/mol weaker. The 2- and 4-pyridones and 2-quinolone exhibit homo-hydrogen bonding whereas their thio analogues do not. The stabilization energy of the 2-thiopyridonyl radical was estimated to be 17 kcal/mol greater than that of the 2-pyridonyl radical, which explains the much greater ease with which esters of N-hydroxy-2-thiopyridone compared to esters of N-hydroxy-2-pyridone produce radicals in the Barton reaction.