Aspects of the stability of isoindoles derived from the reaction of o-phthalaldehyde-ethanethiol with primary amino compounds.

The stability of a series of fluorescent isoindoles formed under analytical conditions following the reaction of o-phthalaldehyde (OPA) and ethanethiol (ET) with a series of primary amines is reported. Increasing the bulk and degree of substitution of the isoindole N-substituent resulted in substantial increases in isoindole stability. The effects of excess reagents on isoindole stability is examined and OPA is observed to accelerate isoindole degradation whilst ET provides a stabilizing effect. Comparison with previously reported data involving the use of 2-mercaptoethanol revealed that ET clearly forms the more stable isoindole derivatives, i.e. a minimum of five-fold improved stability based on the time for 10% degradation to occur. Identification of the major degradation product together with kinetic data suggests that degradation proceeds via autoxidation.