Graduation Year
2026
Document Type
Campus Only Senior Thesis
Degree Name
Bachelor of Arts
Department
Chemistry
Second Department
Philosophy
Reader 1
Daniel O'Leary
Reader 2
Thomas Vasquez
Terms of Use & License Information
Rights Information
© 2026 Lijinghan Chen & Daniel J. O'Leary
Abstract
Hydrogen bonding is a fundamental noncovalent interaction that governs molecular stability, biological activity, and chemical reactivity. While isotope effects on hydrogen bonding in hydroxyl systems have been extensively studied using Nuclear Magnetic Resonance (NMR) methods, the analogous behavior in O–H···F systems remain largely unexplored. This thesis describes the synthesis and computational investigation of fluorinated bicyclic cage molecules designed to probe intramolecular O–H···F hydrogen bonding through isotopic substitution experiments. Monofluorination of the hydroxyl cage precursor was successfully achieved using DAST as the deoxyfluorination reagent, yielding a racemic mixture of axial and equatorial monofluorinated cage isomers in acceptable yield. Successful fluorine substitution was confirmed by ¹⁹F NMR, ¹⁹F NMR with proton decoupling, and ¹H NMR experiments. However, subsequent attempts to remove the benzyl ether protecting group to access the free hydroxyl fluoride compound for isotope-substitution studies were unsuccessful, as ¹⁹F NMR analysis of the deprotection products revealed residual and unexpected fluorine-containing species. Attempts to synthesize the corresponding difluorinated compound were also unsuccessful, narrowing the scope of the study to the monofluorinated system.
Complementary Gaussian geometry optimization and frequency calculations (B3LYP/6-31+G(d)) were performed on six structurally related molecules to evaluate the role of fluorine positioning on molecular stability and hydrogen bonding. The equatorial monofluorinated conformer was found to be the most thermodynamically stable species, with the spatial proximity of the fluorine and hydroxyl groups identified as a key determinant of hydrogen-bond strength. The energy differences between isomers suggest that separation of axial and equatorial fluorine isomers may be feasible, and the pronounced hydrogen bonding character of the fluorinated system indicates that isotopic substitution experiments employing the SIMPLE NMR method will yield observable and quantifiable isotope shifts. These findings establish a strong foundation for future experimental investigation of isotope effects in O–H···F hydrogen bonding systems.
Recommended Citation
Chen, Lijinghan and O'Leary, Daniel J., "Synthesis and Computational Investigation of Fluorinated Cage Molecules for Probing Isotope Effects on Intramolecular O–H···F Hydrogen Bonding" (2026). Pomona Senior Theses. 376.
https://scholarship.claremont.edu/pomona_theses/376
This thesis is restricted to the Claremont Colleges current faculty, students, and staff.
