Water‐soluble tetraoxa[n.1.n.1]paracyclophanes: Synthesis and host‐guest interactions in aqueous solution

The synthesis of water‐soluble tetraoxa[n.1.n.1]paracyclophanes 1c – 8c and open‐chained model compounds 14c and 15c is described. 1c – 8c possess differently sized cavities of pronounced hydrophobic character as binding site for apolar guests in aqueous solution. In 1c – 8c , spiropiperidinium rings locate the water‐solubility providing quaternary ammonium nitrogens remote from the cavity. The synthesis of water‐insoluble tetraoxa[n.1.n.1]paracyclophanes 18 – 22 is described. The geometry of host compounds 1c – 8c is discussed in terms of CPK molecular models. The comparison of the 1 H NMR spectra in CDCl 3 and [D 6 ]benzene of the macrocycles 19 – 22 with the spectra of the open‐chained analogues 26a – c and 28 did not indicate a specific cavity effect on „aromatic solvent‐induced shift” (ASIS). – The aggregation behaviour of 1c – 3c, 8c and 14c in aqueous solution was studied by 1 H NMR spectroscopy and the critical micelle concentration (CMC) of these compounds was determined. – Below the CMC of host and guest, complexation in aqueous solution between hosts 1c – 8c and apolar guests was investigated by fluorescence and 1 H NMR spectroscopy. Host‐guest association constants K a (1 · mol −1 ) for 1:1 complexes were determined from fluorescence titrations. 1 H NMR investigations with hosts 1c – 3c and differently sized guests demonstrated that geometrical host‐guest complementarity is a prerequisite for complexation. Remarkable differences of the changes of the chemical shifts upon complexation (Δδ) were observed for the protons of the guest in aqueous solutions of host 2c and a series of para ‐substituted toluenes 33a – 1 . The different Δδ‐values indicate different degree and strength of complexation and are best explained in terms of a considerable contribution of van der Waals interactions to the free energy of complexation.