Efficient synthesis and astonishing supramolecular architectures of several symmetric macrolactams

The synthesis of four C(n) symmetric macrocyclic lactams cyclo-[NH-CH(2)-CH=CH-CH(2)-CO](n) (1, n=2; 2, n=3; 3, n=4) and cyclo-[NH-CH(2)-CH(2)-CH=CH-CO](3) (4) has been achieved by two approaches. A linear route leads to precursors that are subsequently macrocyclized in a separate step. The second, convergent approach relies on the symmetry of the targets: it includes suitably activated subunits, which are subjected to macrocyclization conditions. The subunits first oligomerize, then cyclize to form either pure macrolactams or mixtures. The macrolactam units 1, 2 and 4 stack on top each other through weak interactions (hydrogen bond and van der Waals), to form endless square, rectangular and triangular prisms, respectively. These stacks are further packed side by side in crystals grown from isotropic media. The overall dipoles in the crystals from lactams 1 and 4, which result mostly from the alignment of amide groups, are zero and large, respectively. Macrolactam 2 displays an astonishing isomorphism when allowed to cool down in anisotropic liquid crystal solutions. Large hollow hexagonal tubes are then obtained through a fractal process. Contrary to the three previous rings, 3 yields crystals where prisms of any shape are absent.