REACTIONS OF CHARGED SUBSTRATES .5. THE SOLVOLYSIS AND SODIUM-AZIDE SUBSTITUTION-REACTIONS OF BENZYLPYRIDINIUM IONS IN DEUTERIUM-OXIDE

Second-order rate constants and activation values were measured for th e reactions with NaN3 of a series of 4-Y-substituted (Y=MeO, Me, H, Cl , and NO2) benzyl 3'-Z-substituted (Z=CN, CONH2, H, F, Ac) pyridinium chlorides in deuterium oxide. 3'-Cyanopyridine substrates reacted much faster than nicotinamide and pyridine substrates; in the pyridine ser ies the 4-Me, 4-H, and 4-Cl benzyl analogs did not react for up to 6 m onths at 96 degrees C in 1.7 M NaN3. The 3'-cyanopyridine substrates d o not exhibit borderline kinetic behavior, but the nicotinamide substr ates do. The Hammett plot is flat for the NaN3 reaction of 3'-cyanopyr idine substrates and increasingly V-shaped for the nicotinamide and py ridine substrates. The values of beta(LG) (four-point plot) for the Na N3 reaction of the 4-MeO benzyl substrates is -1.45, which is usually interpreted as being a very ''late'' activated complex. Two-point Bron sted ''plots'' for the other benzyl derivatives and for two N-methylpy ridinium ions give values of beta(LG) in the same range. The second-or der rate constant and activation values for N-methyl-3'-cyanopyridiniu m iodide are within the same range as those for the benzyl substrates. For the hydrolysis reaction, the Hammett plot is linear for 3'-cyanop yridine substrates (rho(+)=-1.24) and flat for the nicotinamide substr ates. The extent of hydrolysis of 0.005-0.05 M solutions of the 3'-cya nopyridinie substrates depended on the initial concentration of substr ate, and hydrolysis was slowed significantly or stopped completely in the presence of exogenous 3-cyanopyridine. These results show that an equilibrium is established among the products for the 4-MeO, 4-Me, 4-H , and 4-Cl substrates; the 4-NO2 substrate reacted too slowly to disce rn any difference. Data for the extent of hydrolysis were fitted by an equation derived assuming the equilibrium. Despite this limitation on a classic test of mechanism, the rates and rho values are consistent with direct displacement by solvent and not with a unimolecular proces s, These results, which are rationalized in terms of the Pross-Shaik m odel, suggest that there are no ion-dipole complex intermediates in th e benzyl series and show that borderline kinetic behavior is a functio n of leaving group ability and is not necessarily related to a change in mechanism, A computational approach was used to evaluate anomalous PLG values for the hydrolysis and nucleophilic substitution reactions of the methypyridinium ion substrates. It was found that neither the N u-substrate bond lengths nor the difference in charge matched the beta (LG) values, The value of Delta Delta S-double dagger of -15 gibbs/mol between (4-methoxybenzyl)-3'-cyanopyridinium chloride and the corresp onding dimethylsulfonium chloride in the NaN3 reaction, which is the r esult of the solvation of the pyridine at the transition state and the lack of solvation of SMe(2), is used to argue that the source of NAD( +) glycohydrolase ''catalysis'' of NAD(+) bond cleavage is the result of desolvation of the leaving group upon binding.