Reactivity of biologically important reduced pyridines: Part 9. Effect of substitution on rotational energetics in 1-phenyl-1,4-dihydropyridine, the 1-phenylpyridinium cation and related systems

Abstract

The effect of substitutional manipulation of 1-phenyl-1,4-dihydropyridine, 1-phenyl-1,4-dihydronicotinamide, the 1-phenylpyridinium cation and the 1-phenylnicotinamide cation on rotational tractability was examined using the AM1 molecular orbital approximation. The 1-phenyl-1,4-dihydropyridines are associated with energy barriers of almost equal magnitude at planarity and perpendicularity. Substitution at the 4-position of the phenyl moiety with electron-withdrawing functionalities acted to increase the barrier at 90° ( E 90) and decrease the energy of the planar form ( E 0) relative to the unsubstituted compounds. Electron-donating species had the opposite effect. The interannular C-N bond had decidedly more double bond characteristics than the parent system when a nitro substituent was present and decidedly less when a dimethylamino substituent was present. Changes in atomic orbital contributions to the highest occupied molecular orbital (HOMO) were fairly independent of substitution. The quaternary derivatives were characterized by a significantly higher E 0 than E 90 for all substituents examined. In addition, the pattern of atomic orbital contributions to the HOMO was highly dependent on the substituent. Finally, reactivity of the dihydropyridines towards one-electron oxidants such as potassium ferricyanide may be affected by phenyl ring rotation, as this parameter directly influences the HOMO energy and, according to Koopmans theorem, the vertical ionization potential.