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

Abstract

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 (Ir^^k1__k2) were determined using NMR and UV spectroscopies, and both methods gave the almost identical pseudo first-order rate constants (kobs=k1+k2) of 5.4×10-4s-1. The ratio of I to II at equilibrium, estimated by an NMR method in chloroform-d1, was 1 : 1 and 7 : 1 in methanol-d4.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-flow apparatus. The rate (IrII) in the alkaline region was faster than that (IH+ r IIH+) in the acid region, where IIH+ represents an N-protonated oxazolidine form of II.