Applications of NMR techniques: The anomeric effect and secondary deuterium isotope effects

This dissertation is comprised of three separate projects. In each chapter, a relevant question in physical organic chemistry is studied using NMR techniques. The first two chapters involve the use of a highly accurate NMR titration method. In chapter 1, this titration method is used to probe the anomeric effect. A series substituted glucosylanilines were synthesized and subjected to NMR titration. These compounds were chosen because the localization of the positive charge in the anomeric position can be altered by changing the substituent aniline. A series of similarly substituted t-butylcyclohexylanilines were also titrated to isolate the anomeric and steric effects. This study showed that the effect of N-protonation is to increase the effective steric bulk of an anilino group, which favors the equatorial conformer, and also to enhance the anomeric effect, which favors the axial. Moreover, this increase and this enhancement both increase as the positive charge becomes more localized.; In chapter 2, the NMR titration method was used to study the secondary β deuterium isotope effect on amine basicity. Various isotopologues of methylamine, dimethylamine, pyrrolizidine, and 2-benzyl-2-azabicyclo[2.2.1]heptane were subjected to NMR titration. The titrations of these molecules allowed for the measurement of the effect of increasing deuterium substitution on the secondary β deuterium isotope effect. The titrations showed that each deuterium substitution changes the pK_a by an average of ca. 4%. In addition, these titrations elucidated the effect of changing the dihedral angle between the nitrogen lone pair and the deuterium on the secondary β deuterium isotope effect. Variable temperature NMR experiments showed that the secondary β deuterium isotope effect is temperature dependent and arises entirely from the enthalpy.; In chapter 3, the method of isotopic perturbation of equilibrium was used to answer a long standing question of the symmetry of 1,6-dioxa-6aλ 4-thiapentalene. A mixture of unlabeled and selectively deuterated 1,6-dioxa-6aλ4-thiapentalene was synthesized, and the deuterium-induced isotopic shifts were measured using 13C NMR spectroscopy. The interpretation of the observed isotopic shifts allowed for the unequivocal determination of the C_2v symmetry of this molecule.