Five-membered rings. II. Inter and intramolecular reactions of simple amines with N-substituted phthalimides. Methylamine as a reagent for removal of a phthaloyl group from nitrogen

Abstract

A reexamination of the literature on inter and intramolecular reactions of amines with N-substituted phthalimides has led to the demonstration that methylamine is a convenient reagent for removal of a phthaloyl protecting group from nitrogen at room temperature. Application of this procedure (first described in 1896) to the Gabriel synthesis of primary amines and to peptide synthesis is recommended. The simplicity of the reaction is a consequence of the consecutive occurrence of two unexpectedly rapid processes: (1) methylaminolysis of one of the imide bonds; (2) intramolecular catalysis, by an N-methylamido group, of the hydrolysis or aminolysis of an adjacent phthalamido linkage.Some unsuccessful attempts to prepare 2-aminoethylphthalimide are also described.