Mechanism of Synthesis of Tröger and Spiro-Tröger Base Derivatives Starting from Naphthyl- and Anthracenylamines: A Computational Study

Tröger’s bases (TB) have enormous applicability in different areas of science and technology. The mechanisms of reaction of different aminoaromatics with formaldehyde in acid media are described in depth using DFT calculations and model synthesis from our group. When different naphthylamines and anthracenylamine were used, a mixture of products was obtained, highlighting the corresponding TB, acridine and a novel isomer of TB, called SpiroTB, depending on the amino precursor and reaction conditions. Using methyl-6-amino-naphthalene-2-carboxylate, ten possible synthesis pathways for TB, SpiroTB and acridine were explored thoroughly on their free energy surfaces. The most likely pathways were also evaluated for 2-aminonaphthalene, 2-aminoanthracene and 2-methoxy-6-amino-naphthalene. It was found that the first formaldehyde enters on a carbon ortho to the amino and the distribution of products is driven by the relative energies of the transition states required to form the methylene bridge between two aromatic carbons and/or between an ortho carbon and the nitrogen of the second aminoaromatic. The absence of spiroTB starting from 4-bromoaniline was also explained.