Complex Isomerization of Ketoses: A (13)C NMR Study of the Base-Catalyzed Ring-Opening and Ring-Closing Rates of D-Fructose Isomers in Aqueous Solution

Article abstract of DOI:10.1021/ja00300a041

In the present study, the isomerization of D-<2-(13)C>fructose has been characterized under alkaline conditions with (13)C NMR spectroscopy.No detectible resonances arising from the open-chain hydrate or α-D-fructopyranose could be observed in (13)C NMR spectra acquired above pH 7 and between 17 and 50 deg C.Resonances in spectra arising from the (13)C-enriched carbon of the α-furanose and β-furanose and the acyclic keto form of D-fructose were observed to broaden drastically with increasing pH or temperature while, in the same spectra, the line width of the anomeric carbon resonance of the β-pyranose form remained less than 2 Hz. Apparent first-order rate constants for ring opening of the α- and β-furanose forms of the sugar (k_αf,a.c,k_βf,a.c) were determined by fitting measured line widths to a model for three-site exchange.At all pH values and temperatures studied, it was found that k_βf,a.c was nearly twice as large as k_αf,a.c.Second-order rate constants for furanose ring opening were determined from the pH dependence of the apparent first-order rate constants and were found to be (2.88 +/-0.5)E6 and (3.6+/-0.6)E6 M^-1 s^-1 for ring opening of the α-furanose and β-furanose forms, respectively.Thermodynamic activation parameters, ΔH^<*>, ΔG^<*>₂₉₈, and ΔS^<*>₂₉₈, were determined from the temperature dependence of k_αf,a.c and k_βf,a.c at pH 8.4.Under these conditions, ΔS^<*>₂₉₈ was found to be positive for both furanose ring-opening reactions, in marked contrast to the large negative ΔS^<*>₂₉₈ determined from furanose ring-opening rates of D-galactose, D-threose, D-erythrose, and 2-deoxy-D-ribose under acidic conditions.The positive ΔS^<*>₂₉₈ values have been rationalized in terms of a model involving the organization of polar solvent around the stabilized D-fructofuranose anions. Values of ΔH^<*>, ΔG^<*>₂₉₈, and ΔS^<*>₂₉₈ characterizing interconversions between cyclic structures and between cyclic and acyclic forms were determined from the temperature dependence of equilibrium constants at pH 8.4.In all cases, ΔG^<*>₂₉₈ is determined both in sign and magnitude by ΔH^<*>.Apparent first-order ring-closing rates to D-fructofuranoses were determined from ring-opening rate constants, k_αf,a.c and k_βf,a.c, and corresponding equilibrium constants, K^eq_αf,a.c and K^eq_βf,a.c.At all temperatures studied, the ring-closing rate to β-fructofuranose was found to be roughly five times that of the corresponding rate to the α-furanose form.Inversion-transfer (13)C NMR experiments were carried out on D-<2-(13)C>fructose at pH 8.4 and 27 deg C in order to further characterize the relatively slow β-pyranose ring-opening and ring-closing rates (k_βp,a.c and k_a.c,βp).From inversion-transfer data and equilibrium intensities, an upper limit of 0.1 s^-1 was determined for k_βp,a.c and 20 s^-1 for k_a.c,βp.Under identical conditions, ring-closing rate constants to the α- and β-furanose forms were found to be about 80 and 500 s^-1.