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Stability of the 1,3‐substituted 1,4‐dihydropyridines: Substituent effects on the acid catalyzed hydration and oxidation reactions
Author(s) -
Pop Emil,
Huang MingJu,
Brewster Marcus E.,
Bodor Nicholas
Publication year - 1994
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.560520713
Subject(s) - chemistry , substituent , catalysis , reactivity (psychology) , proton , substrate (aquarium) , computational chemistry , proton affinity , molecule , molecular orbital , ionization , polar effect , electron affinity (data page) , medicinal chemistry , organic chemistry , protonation , ion , medicine , physics , alternative medicine , oceanography , pathology , quantum mechanics , geology
1,3‐Substituted‐1,4‐dihydropyridines easily add water to the 5,6‐double bond in acid catalysis resulting in 6‐hydroxy‐1,4,5,6‐tetrahydropyridines. The influence of various substituents in position C‐5 and C‐6 over the hydration of 1‐methyl‐1,4‐dihydromethylnicotinate, used as a model compound, was investigated in the framework of the AM 1 molecular orbital approximation. Since the rate‐limiting step of the reaction is a proton transfer from the acidic species to the C‐5 position of the substrate, calculated proton affinities ( PA ) were used as reactivity indexes. The results, in agreement with experimental evidences, indicated that electron‐donating (+I) substituents increase the PA and destabilize 1,4‐dihydropyridines towards hydration, while electron‐withdrawing (−I) groups have the opposite effect. Calculated vertical ionization potentials (Ip) indicate that similary +I groups facilitate the one‐electron oxidation, while −I groups stabilize the molecules toward this reaction. Several molecular properties derived from the principle of maximum hardness were also used for the investigation of the stability of the dihydropyridines. © 1994 John Wiley & Sons, Inc.