RELETIVE REACTIVITIES OF HETEROAROMATIC CATIONS TOWARDS REDUCTION BY 1,4-DIHYDRONICOTINAMIDES

Article abstract of DOI:10.1016/S0040-4020(01)87506-2

Kinetic data are reported for the equilibration of the 1-methyl-3-nitropyridinium cation with its pseudobase (hydroxide adduct) and for the reduction of this cation by 1-benzyl-1,4-dihydronicotinamide.The C-2 hydroxide adduct is kinetically controlled product (pK_R+ = 11.6) when this pyridinium cation is mixed with aqueous base, however, this species rearranges to the C-4 adduct as the thermodynamically more stable product (pK_R+ = 9.42).The pH-dependence of this equilibration may be analyzed to give k_OH = 1600 M^-1s^-1 for hydroxide ion attack at C-4 of this cation.Reduction of this pyridinium cation by 1-benzyl-1,4-dihydronicotinamide appears to occur exclusively at C-4 with second-order rate constant k₂ = 0.72 M^-1s^-1 and k₂^H/k₂^D = 2.0 in 20percent CH3CN - 80percent H2O, ionic strength 1.0, 25 deg C.The reactivities of pyridinium, quinolinium, isoquinolinium, acridinium and phenanthridinium cations of pK_R+ = 10.0 towards both hydroxyde ion and 1-benzyl-1,4-dihydronicotinamide are evaluated.Relative reactivities (k₂/k^OH) for these two processes are shown to be acridinium : quinolinium (C-4) : pyridinium (C-4) : quinolinium (C-2) : isoquinolinium : phenantridinium = 1.6x1E5 : 3400 : 80 <4 : 1.0 : O.7 for predominantly aqueous reaction media.These data support the hypothesis that formation of 1,2-dihydropyridine systems upon reduction of heteroaromatic cations by 1,4-dihydronicotinamides occurs via direct one step hydride transfer, while formation of 1,4-dihydropyridines in such processes occurs preferentially by a mechanistically more complex process involving electron transfer.