Kinetics of the reduction of nicotinonitrile cations by 1,4-dihydronicotinamides

Abstract

. Can. J. Chem. 63, 1245Chem. 63, (1985. The rates of reduction of a series of 1-(Z-benzyl)nicotinonitrile cations by a series of I-(X-benzyl)-l,4-dihydronicotinamides have been studied at 25°C in 20% CH3CN -80% HzO (pH 7.0 (5 mM phosphate), ionic strength 1.0 (KCI)). Spectral studies indicate the formation of 1,4-dihydronicotinonitrile products, without the formation of the isomeric 1,2-dihydro-or 1,6-dihydro-nicotinamide intermediates. Second-order rate constants (kz) for these reductions are closely correlated with the Hammett u constants for X and Z. Thus, for X = H, log kz = 0.630, -1.05, while for Z = 4-CN, log kz = -0 . 6 4~~ -0.65. The close correspondence between these p, and p, values indicates that charge neutralization on the nicotinonitrile cation exactly balances charge generation on the nicotinamide cation product in the rate-determining transition state. Thus the migrating hydrogen species is electrically neutral in the rate-determining transition state, which contrasts with the hydridic transition states previously reported in the reduction of isoquinolinium cations by 1,4-dihydronicotinamides. When 1-benzyl-4,4-dideuterio-1,4-dihydronicotinamide is used as the reductant, primary kinetic isotope effects of 3.0 and 2.7 are observed for the reduction of the I-methylnicotinonitrile and 1-(4-cyanobenzy1)-nicotinonitrile cations, respectively. These data are evaluated in terms of the various mechanistic possibilities for hydride transfer. 1245 (1985).Operant 25"C, dans des solutions a 20% CH,CN -80% HzO, a un pH de 7,O (5 mM de phosphate) et a une force ionique de I , O (KC]), on a dtterminC les vitesses de rkduction d'une skrie de cations (Z-benzyl)-l nicotinonitrile par une serie de (X-benzy1)-l dihydro-1,4 nicotinamides. Des Ctudes spectrales indiquent qu'il y a formation de produits dihydro-1,4 nicotinonitrile, sans formation des intermediaires isomkres dihydro-l,2 ou dihydro-1,6 nicotinamides. Il existe une correlation entre les constantes de vitesse du deuxikme ordre (k,) de ces reductions et les constantes u de Hammett des substituants X et Z. Ainsi, pour X = H, log kz = 0 , 6 3 1~~ -1,05, alors que pour Z = CN-4, log k2 = -0,640, -0,65. La bonne correspondance entre ces valeurs de p, et de p, indique que, dans 1'Ctat de transition determinant la vitesse de la rkaction, la neutralisation de la charge du cation nicotinonitrile contrebalance exactement la gCnCration de la charge sur le produit cationique nicotinamide. Dans 1'Ctat de transition qui determine la vitesse de la rkaction, l'hydrogene qui migre est Clectriquement neutre et ceci est en opposition avec les Ctats de transition impliquis dans les reductions par les hydrures dont il Ctait fait mention dans les rapports antCrieurs sur la rCduction de cations isoquinolinium par les dihydro-1,4 nicotinamides. Lorsqu'on utilise la benzyl-1 dideuttro-4,4 dihydro-1,4 nicotinamide comme reducteur, on observe des effets isotopiques primaires de 3,O et 2,7 respectivement pour les riductions des cations mCthyl-1 nicotinonitrile et (cyano-4 benzyl)...

Kinetics of hydride transfer between nitrogen heteroaromatic cations

“…In initial experiments, the time dependences of the electronic absorption spectra of equimolar mixtures of the reactants were obtained for each of the reactions in eqs. [2]- [8]. In all cases, as indicated below, the spectral observations were consistent with the reaction products of eqs.…”

“…[2]- [4]), and the reduction of these three cations and also the lo-methylacridinium cation (A+) by 5,6-dihydro-5-methylphenanthridine (PH) (eqs. [5]- [8]) in 20% acetonitrile in water, buffered at an appropriate pH as described in the experimental section, at ionic strength 1.0 and 25°C. In initial experiments, the time dependences of the electronic absorption spectra of equimolar mixtures of the reactants were obtained for each of the reactions in eqs.…”

“…[8]) is known to give 9,lOdihydro-10-methylacridine and the 5-methylphenanthridinium cation. The spectrum of our product mixture is consistent with this result.…”

“…Many of these investigations have utilized 1,4-dihydronicotinamides for the reduction of a variety of pyridinium (1)(2)(3)(4)(5)(6)(7)(8)(9), quinolinium (10)(11)(12)(13)(14), isoquinolinium (15,16), and acridinium (1 1, 13, 17-28) cations, since such reducing agents are most closely related to the biological NADH and NADPH species. However, a variety of 1,4-dihydroquinolines (1 1, 13, 24, 25, 29), 9,lO-dihydroacridines (1 1, 13, 24, 25, 30, 31), and 5,6-dihydrophenanthridines (1 1, 13, 30, 32) have also been used as hydride donors in the continuing investigations of "model nicotinamide-coenzyme reactions".…”

“…[8] under pseudo-first-order conditions, because of the long wavelength absorbance by the 10-methylacridinium cation and the limited solubility of the 5,6-dihydro-5-methylphenanthridine in the predominantly aqueous solvent. Consequently, we have followed the disappearance of the acridinium cation at 416 nm, at similar concentrations of the two reactant species.…”