Synthesis of 1,4,6,10-tetraazaadamantane quaternary derivatives

Abstract

Methods for the preparation of stable 1,4,6,10-tetraazaadamantane quaternary derivatives were developed based on quaternization of a tertiary nitrogen atom in tris(β-oximinoalkyl)amines or isomeric 4,6,10-trihydroxy-1,4,6,10-tetraazaadamantanes. This process constitutes a convenient approach to the introduction of a hydrophilic 1,4,6,10-tetraazaadamantane moiety into lipophilic molecules in order to increase their solubility in water. 4,6,10-Trihydroxy-1,4,6,10-tetraazaadamantane N-oxide was synthesized by the oxidation of the tertiary nitrogen atom in the tris-oxime and subsequent intramolecular cyclotrimerization of the oximino groups. Quantum chemical calculations showed that the quaternization of the annular nitrogen atom led to a considerable stabilization of tetraazaadamantane framework as compared to the open-chain form of tris-oxime.