SYNTHESIS AND PROPERTIES OF MACROCYCLES FROM RESORCINOL, CORRESPONDING DERIVATIVES AND HOST-GUEST COMPLEXES

Structural variations of the metacyclophanes obtained from the condensation of resorcinol with aldehydes RCHO are described, mostly based on the stereoisomer with all R in cis configuration. The basic tetraphenolate (with R = CH3, 1a) shows a cone-conformation as evident e.g. from vicinal C-13-C-C-H-1 coupling constants. Substituents R' in the 2-position of the phenyl rings at the upper rim of the macrocycle are either introduced with the resorcinol derivative used (R' = CH3, COOH), or by Mannich reactions after cyclization (R' = CH(2)NR(2)''), which partially lead to intermediate oxacine formation. Acid-base properties are evaluated with potentiometric and NMR-shift titrations. Mannich products from amino acids such as proline, which are formed without racemization, show no pK differences for the groups at the four equivalent phenyl rings, but three distinct pK values for the deprotonation of OH, COOH, and (NH3)-N-+ substituents; the pK of the latter is two units lower than in proline itself as it is involved in hydrogen bridging. Complexation constants K of such derivatives with Fe3+, CU2+, and Zn2+ show the expected increase with metal ion acidity; they are increased by a power of 5 in comparison to proline. Complexation constants and complexation-induced NMR shifts (CIS values) are determined for 51 complexes, with positively charged organic guest molecules for the basic tetraphenolate skeleton as well as for the aminomethylation derivatives. A temperature dependence study shows that the corresponding equilibrium is driven by Delta H with negligible Delta S contributions. No chiral discrimation is observed upon complexation of e.g. carnitine with the optically active amino acid derivatives. This is in line with CIS and K values obtained with several complexes showing an orientation of the NR(2)'' groups away from the cavity. The COOH substituents R' form strong hydrogen bonds with the adjacent phenolic groups, leading to alternating pseudo-eq. and -ax positions of the phenyl rings. Their interconversion barrier, determined by NMR spectroscopy, is 72 kJ mol(-1); they bind mono- and bis-ammonium ions as function of distance matching. The presence of lipophilic substituents (R = phenyl, benzyl, biphenyl, n-hexyl, n-undecyl) at the bottom of the macrocycle furnishes a second binding center which allows to complex e.g. diethyl ether in water. Coordination of zinc to the proline derivative still allows co-complexation of choline acetate, the hydrolysis of which is not inhibited anymore as it is by the zinc-free macrocycle.