The heterocyclic ring of 4-substituted-1,8-naphthalimides is NOT inert to nucleophilic attack, contrary to earlier reports

Abstract

The heterocyclic ring of N-aryl-4-chloro-1,8-naphthalimides, reported to be resistant to nucleophilic attack, reacts with primary amine nucleophiles at room temperature to give 4-chloro-N-alkyl-1,8-naphthalimides. The reaction is first order in the naphthalimide. The Hammett plot is linear (R² 0.996) with a large positive slope (+3.0), consistent with substantial negative charge development at nitrogen in the activated complex.