NMR studies of host-guest complexes between monocarboxylic acids and amide-based cyclophanes in chloroform

Formation of host-guest complexes with acetic acid and benzoic acid was studied by NMR for amide-based octaazacyclophanes having pendant methyl ester arms; the cyclophanes were tetramethyl 2,9,18,25-tetraoxo-1,4,7,10,17,20,23,26- octaaza[10.10]paracyclophane-4,7,20,23-tetraacetate, its meta-isomer and analogues. Amide NH proton and CH2 proton adjacent to amide C=O in every cyclophane host showed down-field NMR shifts in the presence of the guest acids in CHCl3-d, suggesting the formation of 1:1 complexes in which the carboxyl group of an acid molecule formed two hydrogen bonds with the amide NH and C=O moieties of a host molecule. Since the complex formation competed with the dimerization of the guest acids, the monomer-dimer equilibrium was restudied by NMR and the equilibrium constant was determined to be 330M-1 for acetic acid and 518M-1 for benzoic acid. By using these values, the formation constants of the host-guest complexes were determined to be 8-51M-1. The close contact between the host and guest molecules via hydrogen bonding was consistently confirmed by NMR shifts due to the ring current of aromatic group.