NMR Studies of H2O: N-Phenyl (N-Phenyl-β-D-Glucopyranosylamine) Urokamide Interactions in Dimethyl Sulfoxide at two Fields

Abstract

During the course of NMR structural investigations of the title compound (N-phenyl uronamide) we noticed the presence of a strong H₂O activity-dependent NOE between the small amount of H₂O associated with the carbohydrate's hydroxyl protons in solutions of DMSO-d₆ . The -OH/H₂O off-diagonal t₁ slices displayed a NOESY τ_m-dependence similar to molecules (τ_c = 0.1–5 ns) experiencing slow exchange (1–10 s^?1). From T₁ data at two fields a τ_c for the title compound was calculated to be ca. 0.54 ns at 313 K. The -OH/H₂O exchange rate constant, K, increased from 0.32 to 11.14 s^?1 as the molar ratio of H₂O]:N-phenyl uronamide] increased from ca. 4.5 to 5.2. The latter finding indicated that the -OH/H₂O proton exchange process, which is strongly affected by the translational diffusion of H₂O, diminished as H₂O] approached that which was inherently a complex in the crystalline structure (e.g., C₁₈H₂₀O₅N₂·4H₂O) and was, presumably, tightly hydrogen-bound to the -OH/NH funtional groups. To test this, the title compound was recrystallized from ethanol/2, 2-dimethoxypropane whereupon the bound H₂O was eliminated; the lack of H₂O induced a significant upfield shift in the resonance frequencies of all the exchangable (-OH Δδ=86.33Hz; -NH Δδ=67.84Hz) functional groups relative to the methine protons (CH Δδ=0.25Hz).