Formation and instability of o-phthalaldehyde derivatives of amino acids.

o-Phthalaldehyde reacts with amino acids in the presence of a thiol to give highly fluorescent 1-alkyl-thio-2-alkyl-substituted isoindoles. However, the instability of the derivatives limits the general utility of the reaction. Mechanistic descriptions of isoindole formation and degradation proposed in the last years, which permit a better understanding of the factors affecting isoindole stability, are presented. The use of alternative thiols and o-phthalaldehyde-like reagents is also reviewed.