Amine Bases and Their Complexes in Hydrogen Fluoride

Abstract

Fluorination has had a significant impact on science and technology, particularly in the fields of pharmaceuticals and materials science. Chapter 1 examines the physicochemical properties of fluorine in organic molecules in the context of drug design. It reviews methods to incorporate fluorine, focusing on strategies that boost the nucleophilicity of fluoride by tuning non-covalent interactions and minimise elimination side reactions. Electrophilic fluorination methods are also briefly covered.
Chapter 2 focuses on hydrogen fluoride (HF) as a fluorination reagent, particularly within binary systems such as Olah’s reagent (9HF·py) and Franz’s reagent (3HF·TEA), and their combination to form ternary HF·amine mixtures, where “amine” refers to a combination of pyridine (py) and triethylamine (TEA). The structural and dynamic properties of these systems were investigated using nuclear magnetic resonance spectroscopy and computational modelling, revealing that the solvation environment of the fluoride anion depends strongly on both the identity of the amine base(s) and the HF concentration. Analysis of the resulting fluoride-HF cluster distributions enabled rational predictions of fluoride nucleophilicity and basicity, which were subsequently validated experimentally.
Building on these insights, Chapter 3 introduces a new class of HF reagents based on triarylamines. The chapter outlines the existing roles of triarylamines in chemistry, the rationale for their use with HF, and the experimental determination of both acidity and fluoride nucleophilicity. Para-substituted triarylamines displayed clear correlations between reactivity trends and apparent pKaH values, which are challenging to measure directly in non-aqueous media. A relationship between the apparent pKaH in acetic acid and the oxidation potential in acetonitrile was established, enabling the discovery of an empirical correction that allows for the prediction of the apparent pKaH in HF. Comparative reactivity studies demonstrated that selected nHF·triarylamine mixtures exhibit enhanced performance over aHF gas, highlighting the beneficial role of the triarylamine base.

Date of Award	20 Jan 2026
Original language	English
Awarding Institution	University of Bristol
Supervisor	Alastair J J Lennox (Supervisor)