Kinetics of the Reduction of Isoquinolinium Cations by 1,4-Dihydronicotinamides

Article abstract of DOI:10.1021/jo00133a014

The kinetics of the reduction of a series of 2-methyl-4-X-isoquinolinium cations <4 (X = H, Br, CONH2, COC6H5, CN)> and 2-methyl-5-X-phthalazinium cations <6 (X = H, NO2)> by 1-benzyl-1,4-dihydronicotinamide (5) have been measured in 20percent CH3CN-80percent H2O (v/v) at pH 7, 25 deg C, and an ionic strength of 1.0.Pseudo-first-order rate constants (k_obsd) show kinetic saturation at high concentrations of 4 (X = H and Br), and association constants of 2.1 and 1.5 M^-1, respectively, have been evaluated for 1:1 complex formation.Interpretation of these data and earlier data for the reduction of the 2-methyl-5-nitroisoquinolinium cation (3) in terms of nonproductive complex formation leads to a linear free-energy relationship between the second-order rate constant (k₂) for reduction and pK_R+ for pseudobase formation by these cations: log k₂ = -0.50pK_R+ + 4.9.Substituent effects upon k₂ for the reduction of 3 and 4 (X = CONH2, CN) by 1-benzyl-3-W-1,4-dihydropyridines (W = CN, CONH2, CONHCH3, CON(CH3)2) are similar to the substituent effects for cyanide ion dissociation from the corresponding 1-benzyl-4-cyano-3-W-1,4-dihydropyridines.The current study indicates that the relatively strong 1:1 complexes observed in the reduction of 5-nitroisoquinolinium cations by 1,4-dihydronicotinamides are nonproductive and also provides further evidence in support of a one-step hydride-transfer mechanism for these reactions.