Premium
Relative reactivity of 1,4‐ and 1,6‐dihydronicotinic acid derivatives to radically mediated oxidation—a theoretical and experimental evaluation
Author(s) -
Brewster Marcus E.,
Browne Clinton,
Bodor Nicholas,
Pop Emil,
Huang MingJu,
Balaban Alexandru T.
Publication year - 1995
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560560717
Subject(s) - chemistry , reactivity (psychology) , computational chemistry , reaction rate constant , ferricyanide , homo/lumo , ring (chemistry) , medicinal chemistry , dihydropyridine , standard enthalpy of formation , organic chemistry , molecule , kinetics , medicine , physics , alternative medicine , pathology , quantum mechanics , calcium
Theoretical and experimental studies were performed on a series of 1,4‐ and 1,6‐dihydronicotinic acid derivatives to investigate their relative stabilities and factors contributing thereto. Ferricyanide‐mediated oxidation studies indicated that not only did the 1,4‐dihydropyridine derivatives oxidize more slowly than the 1,6‐isomers, a finding consistent with previously published literature, but also that the ratio of the rates of reaction was constant. Thus, the 1,4‐dihydropyridines oxidized 23‐fold more slowly than did the 1,6‐derivatives. Theoretical studies also indicated that the 1,4‐dihydropyridines were more stable than the 1,6‐isomers, as illustrated by lower calculated heats of formation, and were also more resistant to oxidation, as demonstrated by larger HOMO‐LUMO energy gaps. An examination of the HOMO for the dihydropyridines showed that the 1,4‐isomers were associated with a greater degree of homoaromatic and hyperconjugative stabilization as compared to the 1,6‐dihydropyridines and that these factors did not appear to be significantly affected by substitution. These data suggest that the stabilizing properties associated with the 1,4‐dihydropyridine system (i.e., greater contributions from the sp 3 ring carbon and attached hydrogens) are systematically expressed providing an explanation for the constant difference in experimental reaction rates. © 1995 John Wiley & Sons, Inc.