When Does a Supramolecular Synthon Fail? Comparison of Bridgehead-Functionalized Adamantanes: The Tri- and Tetra-amides and Amine Hydrochlorides

1,3,5-Trisubstituted adamantane carboxamide and amine hydrochloride, Ad­(CONH2)3­·2.5H2O and [Ad­(NH3)3]­Cl3­·H2O (Ad = adamant-n-yl) respectively, crystallized from aqueous solutions, possess crystal structures with predictable H-bonded assembly, consistent with the C3v symmetry of the building blocks. The triamide structure consists of interpenetrated hexagonal networks, sustained by the well-known cyclic H-bonded bis-amide synthon, R22(8), which ensures linear connectivity. The structure of the triamine hydrochloride, assembled through the tetrahedral {RN+H3···(Cl–)3} synthon, features a remarkably symmetric assembly with narrow trigonal pore channels, hosting water molecules. The structures of the tetrahedral 1,3,5,7-tetrasubstituted Ad­(CONH2)4 and [Ad­(NH3)4]­Cl4, obtained similarly, demonstrate a formal prediction failure of synthon-based approach. Instead of the anticipated bis-amide synthon-based diamond network (1.485 g cm–3) analogous to the 5-fold interpenetrated paradigmatic structure of Ad­(COOH)4, a non-interpenetrated assembly, sustained by a dense network of H-bonds, is realized (1.433 g cm−3). Lessened geometric regularity was also found in the tetrahydrochloride salt assembled via 5-connected nodes, {RN+H3···(Cl–)4}, which involve a bifurcated H-bond. The failures of the supramolecular synthons in these simple cases could be interpreted in terms of either symmetry and/or limitations associated with the “synthon density”. A potential machine-learning approach oriented on heuristic retro-supramolecular synthesis relies on such selected high-weight conceptual cases.