SAARBRUCKEN SERIES IN HOST-GUEST CHEMISTRY .27. MECHANISMS OF MACROCYCLE GENESIS - THE CONDENSATION OF RESORCINOL WITH ALDEHYDES

The title reactions proceed in high yields without high dilution techniques as long as substituents allow hydrogen bonds between the phenolic units and do not lead to steric hindrance. Isomerization rates for three epimeric cyclophanes, including a hitherto undiscovered one, are obtained by least-squares fit with integrated rate equations. The buildup sequences of oligomers, polymers, and macrocycles are analyzed by numerical stepwise integration with 50 rate constants, based on the fit of time-concentration curves of seven identified structures that were followed by proton NMR. Macrocyclization is favored by the following: (a) fast degradation of oligomers, (b) fast ring closure of tetramers, as well as (c) fast chain growth to these in comparison to ring opening. Homogeneous reaction conditions, here with methanol as solvent, are essential not only for the quantitative analyses, but also for the solubility of polymers in view of their degradation and for the observation of new stereoisomers. Molecular mechanics calculations with the CHARMm field and model considerations identify the factors responsible for the unique preference for cyclization over polymerization. Both hydrogen bonds between the phenolic units and 1.5 interactions between phenolic groups and the methyl substituent-stemming from the acetaldehyde-strongly favor folded conformers with small distances around d = 3.3-4.6 angstrom between the terminal reacting centers in comparison to stretched conformations with d = 12.2-18.3 angstrom.