Document Type

Dissertation

Date of Award

2024

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Haoran Sun, Pere Miro

Abstract

Fluorination of organic molecules can alter their stability, lipophilicity, and hydrophobicity. As a result, organofluorine compounds have gained significant attention in various fields due to their unique physical, chemical, and biological properties and diverse applications including pharmaceuticals, agrochemicals, materials, and electronics. Deoxyfluorination is commonly used to convert oxygen-containing functional groups like alcohols, phenols, aldehydes, ketones, and carboxylic acids into corresponding monofluoro alkyl and aryl fluorides, difluoromethyl, difluoromethylene, and trifluoromethyl groups with various deoxyfluorination reagents, such as diethylaminosulfur trifluoride (DASTTM), DeoxoFluor®, PhenoFluorTM, PyFluorTM, and FluoLeadTM. In the case of secondary alcohols, a major challenge with these reactions is that fluoride basicity can drive an elimination reaction to form the corresponding alkenes as unwanted products during the deoxyfluorination process. Modulating the basicity of the fluoride while increasing, or at least, maintaining the fluoride nucleophilicity to achieve the desired fluorination product is of great interest for many applications. In this study, we activated secondary alcohol with tetrafluorophthalonitrile (TFPN) through a nucleophilic aromatic substitution to form an aryl ether intermediate that could undergo either substitution or elimination reactions with fluoride to give corresponding alkyl fluorides or alkenes. We further explored the possible reaction mechanism with computational chemistry approach with a long-term goal of identifying possible ways to modulating fluoride reactivity.

Keywords

Chemistry

Number of Pages

272

Publisher

University of South Dakota

Available for download on Saturday, January 29, 2028

Share

COinS