Protection of primary amines as N-substituted 2,5-dimethylpyrroles

Abstract

Protection of a primary amine group is achieved by incorporating it into an N-substituted 2,5-dimethylpyrrole system. The method affords protection against strong bases and nucleophiles, heating with concentrated alkali, standard mineral acid work-up conditions, and various other reagents.

Phenyl-, pyridyl-, thiazolyl-, and alkyl-amines have been studied. All give trisubstituted pyrroles in high yield (>80%) by reaction with hexane-2,5-dione. The pyrroles from the first three types are stable to storage; even the N-alkyl compounds can be used without difficulty. Regeneration of the amine group, by treatment with hydroxylamine hydrochloride, is efficient (ca. 80% yield) with the phenyl, pyridyl, and alkyl compounds but less satisfactory (60–65% generally but down to 25% in two cases) with the thiazolyl derivatives.