Artem N. Semakin

Unusual Intramolecular Cyclization of Tris(β-oximinoalkyl)amines. The First Synthesis of 1,4,6,10-Tetraazaadamantanes

An unusual intramolecular cyclization of tris(beta-oximinoalkyl)amines 1 into 4,6,10-trihydroxy-1,4,6,10-tetraazaadamantanes 2 was discovered. Compounds 2 are related to a previously unknown type of heteroadamantanes that contain the cage isomeric to urotropin. A simple three-step synthesis of tetraazaadamantanes 2 and their N-substituted derivatives 3 and 4 from ammonia and aliphatic nitro compounds via the intermediacy of available tris-oximes 1 was developed.

Syntheses based on α-azidooximes: I. Reduction of α-azidooximes

Convenient procedures were developed for selective and exhaustive reduction of α-azido-oximes that were easily prepared from aliphatic nitro compounds. Nitroalkanes were shown to be convenient precursors of β-functionalized amines (1,2-diamines, iminophosphonates, β azidohydroxyl-amines, α-aminooximes).

Syntheses based on α-azidooximes: II. Preparation of 6,7-dihydrotriazolopyrazinones from aliphatic nitro compounds

Abstractα-Azidooximes readily obtained from aliphatic nitro compounds were cleanly converted into previously unknown 6,7-dihydro[1,2,3]triazolo[1,5-a]pyrazin-4(5H)-ones via [3+2]-cycloaddition to dimethyl acetylenedicarboxylate and reduction of the oximino group in forming intermediates.

Synthesis of Tris(ɣ-oximinoalkyl)amines, New Tripodal N4 Ligands

Abstract An original approach to the synthesis of tris(γ-oximinoalkyl)amines was proposed. The suggested synthetic sequence is based on aza-Michael addition of ammonia to methyl vinyl ketone and oximation of obtained products with hydroxylamine or O-alkhylhydroxylamines. The tris(γ-oximinoalkyl)amines may be considered as prospective N4 tripodal ligands. GRAPHICAL ABSTRACT

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

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.

Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia

Exhaustive Michael-type alkylations of amines and ammonia with azoalkenes (generated from α-halohydrazones) were demonstrated as an efficient approach to poly(hydrazonomethyl)amines – a novel class of polynitrogen ligands. An intramolecular cyclotrimerization of C=N bonds in tris(hydrazonomethyl)amine to the respective 1,4,6,10-tetraazaadamantane derivative was demonstrated.