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.