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 the reactions with NaN(3) of a series of 4-Y-substituted (Y = MeO, Me, H, Cl, and NO(2)) benzyl 3'-Z-substituted (Z = CN, CONH(2), H, F, Ac) pyridinium chlorides in deuterium oxide. 3'-Cyanopyridine substrates reacted much faster than nicotinamide and pyridine substrates; in the pyridine series the 4-Me, 4-H, and 4-Cl benzyl analogs did not react for up to 6 months at 96()() degrees C in 1.7 M NaN(3). The 3'-cyanopyridine substrates do not exhibit borderline kinetic behavior, but the nicotinamide substrates do. The Hammett plot is flat for the NaN(3) reaction of 3'-cyanopyridine substrates and increasingly V-shaped for the nicotinamide and pyridine substrates. The values of beta(LG) (four-point plot) for the NaN(3) reaction of the 4-MeO benzyl substrates is -1.45, which is usually interpreted as being a very "late" activated complex. Two-point Brønsted "plots" for the other benzyl derivatives and for two N-methylpyridinium ions give values of beta(LG) in the same range. The second-order rate constant and activation values for N-methyl-3'-cyanopyridinium iodide are within the same range as those for the benzyl substrates. For the hydrolysis reaction, the Hammett plot is linear for 3'-cyanopyridine substrates (rho(+) = -1.24) and flat for the nicotinamide substrates. The extent of hydrolysis of 0.005-0.05 M solutions of the 3'-cyanopyridinie substrates depended on the initial concentration of substrate, 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-NO(2) substrate reacted too slowly to discern 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 process. These results, which are rationalized in terms of the Pross-Shaik model, suggest that there are no ion-dipole complex intermediates in the benzyl series and show that borderline kinetic behavior is a function of leaving group ability and is not necessarily related to a change in mechanism. A computational approach was used to evaluate anomalous beta(LG) values for the hydrolysis and nucleophilic substitution reactions of the methypyridinium ion substrates. It was found that neither the Nu-substrate bond lengths nor the difference in charge matched the beta(LG) values. The value of DeltaDeltaS() of -15 gibbs/mol between (4-methoxybenzyl)-3'-cyanopyridinium chloride and the corresponding dimethylsulfonium chloride in the NaN(3) reaction, which is the result 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.