Metathesis Reaction of Formaldehyde Acetals. Experimental and Computational Investigation of Isomeric Families of Cyclophanes under Dynamic Conditions

The acid-catalyzed transacetalation of cyclophane formaldehyde acetals incorporating m-xylylene units (m-Ci) generates a well behaved dynamic library of oligomeric macrocycles. Effective Molarities (EM) relating to the formation of the lower cyclic oligomers (i = 2-4) were estimated from equilibrium concentrations measured under conditions closely approaching the critical monomer concentration. Comparison with available EM data relating to the formation of the isomeric paracyclophanes p-C-i shows that the metacyclophanes m-Ci are considerably more stable, the stability difference being particularly significant for i = 2. Molecular modeling indicated that incorporation of COCOC moieties in the cyclic structures enforces deviations from the most stable g(+)g(+)/g(-)g(-) conformation. Consistently with experimental results, such deviations are at a maximum for the dimeric paracyclophane p-C-2, and tend to decrease with increasing ring size in both series, Molecular modeling also showed that the stability of the heterodimer m,p-C-2 is comparable to that of m-C-2, which is again in agreement with the results of a cross-experiment in which a mixture of m-C-2 and p-C-2 was allowed to equilibrate.