Stability of o-phthalaldehyde-derived isoindoles.

The degradation of 1-alkylthio-2-alkylisoindoles, generated in situ by reaction of o-phthalaldehyde with primary alkylamines in the presence of selected thiols, was studied under conditions typical of those used in precolumn derivatization applications. In all cases, loss of isoindole followed pseudo first order kinetics and was strongly accelerated by excess o-phthalaldehyde in the reaction mixture. Reactivity toward o-phthalaldehyde was found to be influenced by a number of experimental parameters including thiol structure, thiol concentration, amine structure, solvent composition, and pH. In the absence of excess o-phthalaldehyde, the stability of all derivatives examined was excellent. These results provide a basis for optimization of reaction conditions for maximum derivative stability.