Synthesis of Acyl Fluorides Using the Tribromoisocyanuric Acid (TBCA)/Triphenylphosphine/HF.Pyridine
Year: 2026
Type: article
Abstract: This study reports an efficient Appel‐type protocol for the synthesis of acyl fluorides using tribromoisocyanuric acid (TBCA) and triphenylphosphine in the presence of Olah's reagent (Py.(HF) x ). The reaction conditions were optimized using 4‐nitrobenzoic acid as a model substrate, achieving good yields with minimal reagent quantities. The methodology tolerates a variety of carboxylic acids, including aromatic substrates with electron‐donating or electron‐withdrawing groups and aliphatic acids. The formation of acyl fluorides was confirmed by 19 F NMR spectroscopy, which revealed substituent‐dependent chemical shift variations. Computational studies using DFT and Born–Oppenheimer Molecular Dynamics elucidated a mechanistic pathway involving acylium ion formation and fluorination via a Grotthuss‐like proton hopping mechanism in the HF.pyridine medium. This protocol provides a practical and environmentally conscious approach to acyl fluoride synthesis.
Source: Israel Journal of Chemistry
DOI: 10.1002/ijch.70027
Institution: Universidade Federal do Rio de Janeiro
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,650
OpenAlex ID: W7162035301