Tröger's base Its chemical formula is . Tröger's base and its analogs are soluble in various organic solvents and strong acidic aqueous solutions due to their protonation. It is named after Julius Tröger, who first synthesized it in 1887.
History
Tröger's original research in 1887
Structure and chirality
thumb|left|Enantiomers of Tröger's base: (5S,11S)-enantiomer (above) and (5R,11R)-enantiomer (below)
The nitrogen inversion normally leads to a rapid equilibrium between the enantiomers of chiral amines, that prevents them showing any optical activity. The inversion can be stopped by conformational strain as Tröger's base has demonstrated that nitrogen is capable of forming a stereogenic center in organic molecules. In Tröger's base, this inversion is not possible, and the nitrogen atoms are defined stereogenic centers. The separation of the enantiomers of Tröger's base was first accomplished by Vladimir Prelog in 1944. Prelog performed column chromatography using a chiral stationary phase as a relatively new method that later on gained popularity and became a standard procedure. Tröger's base and its analogs can be resolved by various methods including chiral HPLC or be made as a single enantiomer.
Almost 30 years after Tröger's initial report, Hünlich described another mysterious product obtained from the condensation of formaldehyde and 2,4-diaminotoluene. After almost a century the structure of Hünlich's product was elucidated by X-ray crystallography as a -symmetric amine-carrying analogue of Tröger's base. which can be prevented by the replacement of methano-bridge with an ethano-bridge.
Reactions
thumb|optically active Tröger base analog forms helical superstructures that enables the shown LCD prototype to pass specific wavelengths of light through a pair of parallel (A) and crossed (B) linear polarizers They function as [[ligand|ligands and ligand precursors in coordination chemistry. When the methyl groups are replaced by carboxylic acids or pyridine amide groups a host–guest chemistry interaction can take place between the Tröger's base and other molecules including glycosaminoglycans. It is found that the cavity dimensions are optimal for inclusion of suberic acid but that with a longer acid sebacic acid or a shorter acid adipic acid the interaction is less favorable.
[[File:Azo carrying Tröger's base.jpg|thumb|left|Bisazo Tröger's base analogs as molecular switches and can be used as molecular switches
Synthesis
thumb|upright=1.45|Mechanism of formation of Tröger's base
Tröger's base is of historic interest as was first synthesised in 1887 from p-toluidine and formaldehyde in an acidic solution by Julius Tröger. or hexamethylene tetraamine (HMTA) as formaldehyde replacement.
The reaction mechanism with DMSO as methylene donor for this reaction is similar to that of the Pummerer rearrangement. The interaction of DMSO and hydrochloric acid yields an electrophilic sulfenium ion that reacts with the aromatic amine in an electrophilic addition. Methanethiol is eliminated and the resulting imine reacts with a second amine. Sulfenium ion addition and elimination is repeated with the second amino group and the imine group reacts in an intramolecular electrophilic aromatic substitution reaction. Imine generation is repeated a third time and the reaction concludes with a second electrophilic substitution to the other aromat. Stereoselective, enantiospecific methods have also been introduced for the direct synthesis of optically active analogs of Tröger's base.