Reaction of Thiamin Analogues with Sulfite Ion: An Example of Zero-Order Kinetics

Article abstract of DOI:10.1021/jo00381a018

Although the cleavage of thiamin (vitamin B₁, 1) and N-methyl vitamin B₁ (1a) with sulfite ion is known to be first order in sulfite ion, two molecules of this nucleophile are involved in the complex process.By contrast, the N-methyl analogue 1e having 3-cyanopyridine as a leaving group does not show any kinetic dependence on the sulfite ion concentration.A proton NMR investigation of the reaction mixture clearly shows the formation of a sulfite adduct, reducing the concentration of the quaternized leaving group dramatically.Coupling constants are observed for the first time in a sulfite adduct of a nitrogen heterocycle.The equilibrium constant was estimated from kinetic data to be 5 * 10⁶ M^-1, the highest ever reported.The analogue having nicotinamide as a leaving group has an equilibrium constant of only 62 M^-1.A model pyrimidine having a cyano group in position 5 and a 4-nitrobenzyl group in position 1 clearly adds sulfite mainly at position 6 to form adduct 4a, revealing the likely site of attack of this nucleophile during substitution.