P. Cieplak et al., ELUCIDATING THE ORIGIN OF CONFORMATIONAL ENERGY DIFFERENCES IN SUBSTITUTED 1,3-DIOXANES - A COMBINED THEORETICAL AND EXPERIMENTAL-STUDY, Journal of organic chemistry, 61(11), 1996, pp. 3662-3668
C-13 NMR spectroscopy, ab initio quantum mechanics, and molecular mech
anics have been used to investigate the trans-4-(trifluoromethyl)-2, 2
, 6-trimethyl-1, 3-dioxane chair/twist-boat equilibrium. The molecular
mechanics calculations were based upon the MM3 and AMBER force fields
. A 61-31G basis was used for the ab initio calculations, and MP2 cor
relation corrections were applied. Both the ab initio and AMBER molecu
lar mechanics calculations are consistent with the C-13 NMR chemical s
hift differences for the trans-4-(trifluoromethyl)-2, 2, 6-trimethyl-1
, 3-dioxane conformers. The predicted chair to twist-boat equilibrium
suggested by the MM3 calculations is not consistent with the experimen
tal data. These results support the suggestion by Howard et al. (Howar
d, A. E; Cieplak, P.; Kollman, P. A. J. Comput Chem. 1995, 16, 243-261
) on the critical role of electrostatic interactions in determining th
e chair/twist-boat equilibrium.