Kinetic evidence for the coexistence of zwitterionic (T+/-), neutral (T0) and anionic (T-) intermediates during rearrangement of S-(2-oxotetrahydrofuran-3-yl)-N-(4-methoxyphenyl)isothiuronium bromide to 5-(2-hydroxyethyl)-2-(4-methoxyphenylimino)-1,3-thiazolidin-4-one.

ABSTRACT

The kinetics and mechanism of rearrangement of S-(2-oxotetrahydrofuran-3-yl)-N-(4-methoxyphenyl)isothiuronium bromide (1) into 5-(2-hydroxyethyl)-2-[(4-methoxyphenyl)imino]-1,3-thiazolidin-4-one have been studied under pseudo-first-order reaction conditions in aqueous buffer solutions and in diluted HCl at 25 degrees C. Multiple breaks in the pH profile establish the formation of three different kinetically detectable intermediates T(+/-), T(0), and T(-). Treatment of 1 (pK(a) = 6.7) with base produces reactive isothiourea, which undergoes cyclization to give T(+/-) (rate limiting step at pH < 0.5). Intermediate T(+/-) then undergoes either general acid-catalyzed, concerted (alpha = -0.47) breakdown to 2 (rls at pH 2-3) or a water-mediated proton switch to T(0) which is followed by its general acid-catalyzed breakdown (pH 3-6). The last reaction pathway involves the formation of T(-) either from T(+/-) or from T(0) (pH > 6). The first possibility seems to be more likely because it is in accordance with kinetics observed in basic amine buffers, where the nonlinear increase of the k(obs) with the c(Buffer) changes to a linear increase as a general base-catalyzed pathway is introduced. Coexistence of all three kinetically detectable intermediates is very rare and is possibly due to relatively enhanced stability of these intermediates necessitating participation of an acid for progression to products.