Cyclic tetraureas with variable flexibility – synthesis, crystal structures and properties

Abstract

Macrocyclic molecules containing several amide or urea functions may serve as anion receptors. We describe the synthesis of 32-membered macrocycles, in which four rigid xanthene units (X) and/or diphenyl ether units (D) as flexible analogues are linked viaurea groups. All six possible combinations of these units (XXXX, XXXD, XXDD, XDXD, XDDD and DDDD) were synthesized and two examples were characterised by single-crystal X-ray analyses (DDDD and two structures for XXXD). Both macrocycles showed distinct differences in their overall conformation and consequently in their hydrogen-bonding pattern. Hydrogen-bonded solvent molecules are found for both compounds and intramolecular hydrogen bonds for the two structures of XXXD, but surprisingly no direct intermolecular hydrogen bonds between the macrocyclic tetraurea molecules. The interaction with various anions was studied by ¹H NMR spectroscopy. Stability constants for all tetramers were determined by UV spectroscopy for complexes with chloride, bromide, acetate and dihydrogenphosphate in acetonitrile–THF (3 : 1). The strongest binding was found for XXXD and acetate (log β = 7.4 ± 0.2), the weakest for XXXX and acetate (log β = 5.1 ± 0.5). MD simulations in chloroform and acetonitrile boxes show that all molecules except DDDD adopt very similar conformations characterized by an up–down–up–down arrangement of the spacer groups. Clustered solvation shells of acetonitrile molecules around XXXX and DDDD suggest their preorganization for spherical/planar and tetrahedral/bidentate anions, respectively, which in turn was corroborated by simulation of the corresponding complexes with chloride and dihydrogenphosphate.