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

Abstract

Equilibrium constants (K) for ring inversion equilibria in 2-(RO)-tetrahydropyrans (R=Et, CH 2CH 2,F, CH 2CHF 2 CH 2CF 3) have been determined from 13C nmr spectra recorded at 145–160K in CD 2Cl 2 and CFCl 3/CDCl 3 (85/15 by volume). Additional values of K were obtained at 250–270K from the acid-catalysed equilibration of is - and trans -2- (RO) -4-methyl tetrahydropyran (R as above). Plots of inK against T -1 gave values for ΔH° a→e of -0.26, -0.12, -0.05 and 0.13 kcal mol -1 for R=Et, CH 2CH 2F, CH 2CHF 2, and CH 2CF 3, respectively, in CD 2Cl 2. The corresponding values of ΔH° a→e for CFCl3/CDCl3, as solvent were -0.58, -0.15, -0.07 and 0.21 kcal mol -1, respectively. The derived ΔS° values were -2.33 , -2.22, -2.25 and -2.24 cal K -1 mol -1 , respectively, in CD 2Cl 2, and -4.65, -3.37, -3.30 and -3.03 cal K -1 mol -1 , respectively, in CFCl 3/CDCl 3. The trends in ΔH° values are attributed to modifications of anti-periplanar n-o* stabilization (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 120k–168. However, this finding is a consequence of the higher entropy of axial equatorial conformations; in at least two cases (R=Et and CH 2CH 2F) 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.