Dual Mechanisms of Nucleophilic Substitution of Thiamin Analogs: Estimating the Special Kinetic Effect of Sulfite Ion

The thiamin derivative 4-amino-5-bromomethyl-l,2-dimethylpyrimidinium bromide (2a) reacts with p-nitrobenzenethiolate, thiosulfate, and azide ions and the corresponding 5-chloromethyl derivative, 2b, reacts with thiosulfate and azide ions, each substrate by an SN2 mechanism. Large kinetic leaving group effects (kBr/kCl > 30) are found with thiosulfate and aside ions but not with sulfite ion. With sulfite ion 2a reacts by two competing mechanisms, mainly nucleophilic substitution by the unique multistep SN(AE) route found for thiamin and many of its analogs and also by a competing SN2 mechanism. A linear free energy relationship comparing the reactivities of 2a and benzyl bromide toward a series of nucleophiles shows that the rate acceleration for the SN(AE) route over that for the SN2 pathway is negligible for 2a and sulfite ion.