Uncovering the Mechanism Leading to the Synthesis of Symmetric and Asymmetric Tröger′s Bases

Abstract

Tröger′s bases have been attracting great interest due to their potential applications in nanoelectronics, supramolecular chemistry, molecular recognition, biological activity and auxiliaries for asymmetric synthesis. However, there is still no detailed step by step proposal for the mechanism leading to the production of these compounds available. A set of five model syntheses of symmetric and asymmetric Tröger′s base derivatives starting from substituted anilines and formaldehyde was studied and envisaged as representative for understanding [a] Scheme 3. Calculated mechanistic pathways for the reaction 1 + 1 → 5z. Relative free energies (ΔG 0 ) in kcal/mol. The colours of the arrows correspond to: path I (blue), path II (green), path III (purple), path IV (yellow) and path V (red).

Experimental, Spectroscopic, and Computational Insights into the Reactivity of “Methanal” with 2-Naphthylamines

“…Another expected process for 6a/b ( Scheme 8 ) was the entrance of another methanal molecule. At this stage, a partner of this quinazoline has already been proven as a key intermediate product formed in the last steps of the formation of TBs in the case of anilines as starting amines [ 17 ]. The attachment of the methylene unit involves the formation of an unstable i3 tau intermediate that is rapidly tautomerized to i3 .…”

“…In relevant cases, an in vacuo intrinsic reaction coordinate (IRC) was determined using a mass-weighted step of 0.02 atomic units and by recalculating the Hessian every ten or 20 steps. The procedure was previously described and tested elsewhere [ 17 , 32 ]. For the relative free energies of Scheme 8 , the ΔG° = 0 was taken as the energies of aminals 8a/b plus two methanal molecules to close the mass balance.…”

“…The level of theory and general procedure were previously described for the synthesis of symmetric and asymmetric TBs from anilines as starting reagents [ 17 ]. The procedure for obtaining the VEA s and VIP s to compute the electrophilicity using CAM-B3LYP was described in detail in [ 20 ].…”

“…The calculations presented here form part of our ongoing efforts to identify the best pathways for obtaining Tröger and spiro-Tröger species. A study of the mechanisms leading to the synthesis of these compounds, starting from anilines, has recently revealed important aspects of the mechanisms taking place under strong acid catalysis conditions [ 17 ]. The calculations here focus on neutral conditions with acetone as the model solvent.…”

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

“…[15] On the other hand, it was also possible to setup an asymmetric derivative as a proof of principle pull-push dye, once again, as if it were a donor/π-linked/acceptor system. [16,42] Due to the large number and variability of applications found for these compounds and analogues, many efforts have been made to improve and optimize their synthesis. For this, different solvents were tested, [17] the sources of methylene and the nature of the acids used also were varied [18][19][20][21] and different amino-aromatic compounds (anilines, naphthylamine, aminopirazoles, among others) were used to obtain different families of TBs.…”