EXPERIMENTAL STUDIES OF THE ANOMERIC EFFECT. PART IV. CONFORMATIONAL EQUILIBRIA DUE TO RING INVERSION IN TETRAHYDROPYRANS SUBSTITUTED AT POSITION 2 BY THE GROUPS ETHOXY, 2'-FLUOROETHOXY, 2',2'-DIFLUOROETHOXY, AND 2',2',2'-TRIFLUOROETHOXY

Article abstract of DOI:10.1016/S0040-4020(01)89776-3

Equilibrium constants (K) for ring inversion equilibria in 2-(RO)-tetrahydropyrans (R = Et, CH2CH2F, CH2CHF2, CH2CF3) have been determined from 13C nmr spectra recorded at 145-160 K in CD2Cl2 and CFCl3/CDCl3 (85/15 by volume).Additional values of K were obtained at 250-270 K from the acid-catalysed equilibration of cis- and trans-2-(RO)-4-methyl-tetrahydropyran (R as above).Plots of lnK against T^-1 gave values for ΔH⁰_a->e of -0.26, -0.12, -0.05 and 0.13 kcal mol^-1 for R = Et, CH2CH2F, CH2CHF2 and CH2CF3, respectively, in CD2Cl2.The corresponding values of ΔH⁰_a->e for CFCl3/CDCl3 as solvent were -0.58, -0.15, -0.07 and 0.21 kcal mol^-1, respectively.The derived ΔS⁰_a->e values were -2.33, -2.22, -2.25 and -2.24 cal K^-1mol^-1, respectively, in CD2Cl2 and -4.65, -3.37, -3.30 and -3.03 cal K^-1mol^-1, respectively, in CFCl3/CDCl3. The trends in ΔH⁰ values are attributed to modifications of anti-periplanar n->o* stabilisation (itself partly responsible for endo- and exo-anomeric effects) which occur as the number of electronegative fluorine substituents increases.For all substituents, axial conformations are the most abundant in the temperature range 120 K to infinite.However, this finding is a consequence of the higher entropy of axial conformations; in at least two cases (R = Et and CH2CH2F) it is the equatorial conformation which has the lower enthalpy.The results confirm the importance of studying conformational equilibria over a wide range of temperature.