Kinetics and Mechanism of Tautomerism of a Hydroxy Schiff Base, N-[2-{2-Hydroxyethylimino(methyl)methyl}phenyl]-2-chlorpropamide, in Solution.

The tautomerism between a hydroxy Schiff base (I), the titled compound, and the corresponding ring-closed oxazolidine (II) was kinetically studied in solution. In chloroform, the rates of tautomerism (I reversible arrow(k2)(k1)II) were determined, ed using NMR and UV spectroscopies, and both methods gave the almost identical pseudo first-order rate constants chloroform-d(1), was 1:1 and 7:1 in methanol-d(4). The molecular species of compound I in various pH buffers were deduced by NMR, UV and other spectroscopies. In an acid solution (e.g., pH 3.0) compound I existed as the protonated Schiff base (IH+) at the imine nitrogen atom, and in the alkaline region (e.g., pH 9.0) as the oxazolidine form II. The tautomerism rates in the aqueous solutions were measured by a pH-jump method using a stopped-how apparatus. The rate (I reversible arrow II) in the alkaline region was faster than that (IH(+)reversible arrow IIH+) in the acid region, where IIH+ represents an N-protonated oxazolidine form of II.