1H-NMR Analysis of Intra- and Intermolecular H-Bonds of Alcohols in DMSO: Chemical Shift of Hydroxy Groups and Aspects of Conformational Analysis of Selected Monosaccharides, Inositols, and Ginkgolides

Abstract

The interpretation of 1H-NMR chemical shifts, coupling constants, and coefficients of temperature dependence (δ(OH), J(H,OH), and Δδ(OH)/ΔT values) evidences that, in (D6)DMSO solution, the signal of an OH group involved as donor in an intramolecular H-bond to a hydroxy or alkoxy group is shifted upfield, whereas the signal of an OH group acting as acceptor of an intramolecular H-bond and as donor in an intermolecular H-bond to (D6)DMSO is shifted downfield. The relative strength of the intramolecular H-bond depends on co-operativity and on the acidity of OH groups. The acidity of OH groups is enhanced when they are in an antiparallel orientation to a C−O bond. A comparison of the 1H-NMR spectra of alcohols in CDCl3 and (D6)DMSO allows discrimination between weak and strong intramolecular H-bonds. Consideration of IR spectra (CHCl3 or CH2Cl2) shows that the rule according to which the downfield shift of δ(OH) for H-bonded alcohols in CDCl3 parallels the strength of the H-bond is valid only for alcohols forming strong intramolecular H-bonds. The combined analysis of J(H,OH) and δ(OH) values is illustrated by the interpretation of the spectra of the epoxyalcohols 14 and 15 (Fig. 3). H-Bonding of hexopyranoses, hexulopyranoses, alkyl hexopyranosides, alkyl 4,6-O-benzylidenehexopyranosides, levoglucosans, and inositols in (D6)DMSO was investigated. Fully solvated non-anomeric equatorial OH groups lacking a vicinal axial OR group (R=H or alkyl, or (alkoxy)alkyl) show characteristic J(H,OH) values of 4.5 – 5.5 Hz and fully solvated non-anomeric axial OH groups lacking an axial OR group in β-position are characterized by J(H,OH) values of 4.2 – 4.4 Hz (Figs. 4 – 6). Non-anomeric equatorial OH groups vicinal to an axial OR group are involved in a partial intramolecular H-bond (J(H,OH)=5.4 – 7.4 Hz), whereas non-anomeric equatorial OH groups vicinal to two axial OR form partial bifurcated H-bonds (J(H,OH)=5.8 – 9.5 Hz). Non-anomeric axial OH groups form partial intramolecular H-bonds to a cis-1.3-diaxial alkoxy group (as in 29 and 41: J(H,OH)=4.8 – 5.0 Hz). The persistence of such a H-bond is enhanced when there is an additional H-bond acceptor, such as the ring O-atom (43 – 47: J(H,OH)=5.6 – 7.6 Hz; 32 and 33: 10.5 – 11.3 Hz). The (partial) intramolecular H-bonds lead to an upfield shift (relative to the signal of a fully solvated OH in a similar surrounding) for the signal of the H-donor. The shift may also be related to the signal of the fully solvated, equatorial HO−C(2), HO−C(3), and HO−C(4) of β-D-glucopyranose (16: 4.81 ppm) by using the following increments: −0.3 ppm for an axial OH group, 0.2 – 0.25 ppm for replacing a vicinal OH by an OR group, ca. 0.1 ppm for replacing another OH by an OR group, 0.2 ppm for an antiperiplanar C−O bond, −0.3 ppm if a vicinal OH group is (partially) H-bonded to another OR group, and −0.4 to −0.6 for both OH groups of a vicinal diol moiety involved in (partial) divergent H-bonds. Flip-flop H-bonds are observed between the diaxial HO−C(2) and HO−C(4) of the inositol 40 (J(H,OH)=6.4 Hz, δ(OH)=5.45 ppm) and levoglucosan (42; J(H,OH)=6.7 – 7.1 Hz, δ(OH)=4.76 – 4.83 ppm; bifurcated H-bond); the former is completely persistent and the latter to ca. 40%. A persistent, unidirectional H-bond C(1)−OH⋅⋅⋅O−C(10) is present in ginkgolide B and C, as evidenced by strongly different δ(OH) and Δδ(OH)/ΔT values for HO−C(1) and HO−C(10) (Fig. 9). In the absence of this H-bond, HO−C(1) of 52 resonates 1.1 – 1.2 ppm downfield, while HO−C(10) of ginkgolide A and of 48 – 50 resonates 0.5 – 0.9 ppm upfield.