CHAIR AND TWIST-BOAT CONFORMATIONS OF 1,3-DIOXANES - LIMITATIONS OF MOLECULAR MECHANICS FORCE-FIELDS

The chair to twist-boat equilibrium was evaluated for a variety of trans-4,6-dialkyl-2,2-dimethyl-1,3-dioxanes using C-13. NMR spectroscopy, and these equilibrium constants were used to determine DELTAG, DELTAH, and DELTAS for the reactions. These conformational equilibria were further evaluated using molecular mechanics, semiempirical, and ab initio calculations. Neither MM2 nor MM3 force fields accurately predict the conformational energies of these simple 1,3-dioxanes. The semiempirical method AM1 performs better than PM3, but reasonable agreement with experiment is only found upon going to ab initio methods using a 6-31 G* basis set. These results illustrate that caution should be used when applying current molecular mechanics force fields to carbohydrates and other compounds containing acetal carbons. The trans-4,6-dialkyl-2,2-dimethyl-1,3-dioxanes are finely balanced between chair and twist-boat conformations and provide a sensitive and challenging test of the performance of computational methods.