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...

Site-resolved 2H relaxation experiments in solid materials by global line-shape analysis of MAS NMR spectra

“…In many interesting systems, the available chemical shift range is much smaller; as one example, the total hydrogen chemical shift range for various carbohydrates like cellulose or starch or chitin but also simple sugars [19][20][21][22] is in the order of one ppm. In this paper we extend the 2 H MAS methodology to systems with small chemical-shift differences.…”

“…FT-IR spectroscopy provided indication that two of the possible three (on C2, C3, and C6 carbons) exchangeable hydroxyl groups [34,35] that may get exchanged. In liquid state, the chemical shift difference [19][20][21][22] between those peaks is small and its variation with, for example, solvent is comparable to its value. As concerning the magnitudes of their quadrupole coupling, there is no prior data available; the only related (though, not directly comparable) data are the C-H bond order parameters obtained from residual 13 C-1 H dipole-dipole couplings which show a rather small or negligible (depending on the source of cellulose) difference between C6 residues on one hand and C-2,3 residues on the other hand [36].…”

“…This is also verified by the obtained order of the chemical shifts of the two components, O(6)H has a lower chemical shift in dissolved b-cellobiose [20] and cyclodextrins and maltoheptoses [19] To investigate the limitations of the presented method for extracting reliably spectral parameters such as small chemical shift differences, we have performed some additional simulations. First, 2 H MAS powder spectra were generated in Matlab by integrating the suitable analytical form [41] for two sites with identical line widths (FWHH = 400 Hz), and slightly different quadrupole splittings of 60 kHz and 70 kHz.…”

Relation between the Δ2 effect and the solution conformational entropy of aldohexoses and select methyl glycosides

“…This effect could also be augmented by intramolecular H-bonding between the hydrogen of the OH on C 2 and the oxygen of the aglycon in the methyl-a-glycosides. The latter conclusion is supported by proton nuclear magnetic resonance ( 1 H NMR) studies of a-and b-methyl-gluco-and galactosides in DMSO, where it was found that the coupling constant J(H,OH) and the chemical shift d(OH) for the hydroxyl group at C 2 were larger for methyl-a-glucoside and methyl-a-galactoside than for their b counterparts (Bernet & Vasella, 2000). The same study showed that, in DMSO, the DJ(H,OH) and Dd(OH) between a-and b-methyl-galactosides (again for the OH at C 2 ) were both larger than the corresponding differences between a-and bmethyl-glucosides, and ranked these four glycosides in the order b-MeGlc > b-MeGal > a-MeGlc > a-MeGal with respect to chemical shift at the C 2 OH.…”

Achieving molecular stability of racemic 4-O-benzyl-myo-inositol-1,3,5-orthoformate through crystal formation

“…Vasella and co-workers 24,25 investigated the intramolecular hydrogen bonding in 4 by an analysis of their FT-IR spectra in CCl 4 and DMSO solutions. A strong intramolecular hydrogen bond was observed between the C6-hydroxyl group and the oxygen atom O4 (O6-H69 … O4) while the C2-OH group exhibited weaker hydrogen bonding with the orthoester oxygen atoms O1 and O3 in solution.…”