Tetrabutylammonium Fluoride (ca. 1mol/L in Tetrahydrofuran or 70-75% in Wate)

• Catalog: OFC429414
• CAS: 429-41-4
• Category: Nucleophilic Fluorination Agents
• Synonyms: TBAF (ca.1mol/L in Tetrahydrofuran); TBAF (70-75% in Water)
• MDL Number: MFCD00011747

• IUPAC Name: tetrabutylazanium;fluoride
• InChI: InChI=1S/C16H36N.FH/c1-5-9-13-17(14-10-6-2,15-11-7-3)16-12-8-4;/h5-16H2,1-4H3;1H/q+1;/p-1
• InChI Key: FPGGTKZVZWFYPV-UHFFFAOYSA-M
• Isomeric SMILES: CCCC[N+](CCCC)(CCCC)CCCC.[F-]
• EC Number: 207-057-2
• Reaxys Registry Number: 3570522

• Molecular Formula: C16H36FN
• Molecular Weight: 261.47
• Flash Point: -17 °C
• Density: 0.903 g/mL (25 °C)
• Appearance: Colorless to red to green clear liquid
• Solubility: Soluble in water
• Storage: 0-10 °C; Store under inert gas
• Stability: Air sensitive

• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 12
• Exact Mass: 261.28317831 g/mol
• Monoisotopic Mass: 261.28317831 g/mol
• Topological Polar Surface Area: 0Ų
• Heavy Atom Count: 18
• Formal Charge: 0
• Complexity: 116

• HS Number: 2923.90.0100

Case Study

Tetrabutylammonium Fluoride for Zirconium Hydride Catalysis in Chiral Benzylamine Synthesis

Aloiau A. N., et al. The Journal of Organic Chemistry, 2024.

Tetrabutylammonium fluoride (TBAF) has been effectively utilized as a key activating agent in the catalytic reduction of chiral benzylamines, specifically in the context of zirconium hydride catalysis. This method, designed for drug discovery applications targeting oncogenic drivers of cancer, employs inexpensive and bench-stable zirconocene dichloride as the catalyst precursor. The activation of zirconocene dichloride with TBAF under ambient conditions facilitates the formation of a zirconocene fluoride complex, which is critical in generating the metal hydride necessary for the reduction reaction.
The experimental procedure involved using TBAF to initiate the formation of zirconocene fluoride, which subsequently activated the zirconium hydride for a selective reduction process. The reaction demonstrated high diastereoselectivity and chemoselectivity, crucial for synthesizing key intermediates relevant to medicinal chemistry and natural product synthesis. The method was tested on sulfinyl ketimines and carbonyl compounds, providing valuable insights into its potential application in the synthesis of complex molecular scaffolds.

Tetrabutylammonium Fluoride (TBAF) for the Sulfurization of 2,3-Diarylcyclopropenethiones and 2,3-Bis(4-chlorophenyl)cyclopropenone

Mlostoń G, et al. Journal of Fluorine Chemistry, 2023, 270, 110170.

The use of tetrabutylammonium fluoride (TBAF) in the activation of elemental sulfur has proven to be highly effective for the selective sulfurization of various thioketones and ketones. Upon treatment of elemental sulfur with TBAF in THF under an argon atmosphere at room temperature, the sulfur undergoes activation through ring opening, resulting in the formation of a highly reactive fluoropolysulfide anion (FSx‒). This intermediate, characterized by its red color, readily reacts with sterically congested 2,3-diarylcyclopropenethiones, leading to the selective formation of five-membered 3H-1,2-dithiole-3-thiones in excellent yields.
In the experimental procedure, elemental sulfur was suspended in dried THF, and TBAF (1.0 M in THF) was added dropwise. After stirring for 10-15 minutes, the resulting red solution was treated with a thioketone, and the reaction was monitored by TLC until the complete conversion of thione was achieved. The product was purified via silica gel column chromatography, resulting in high yields of the corresponding 3H-1,2-dithiole-3-thiones. Similarly, when 2,3-bis(4-chlorophenyl)cyclopropenone was subjected to the same sulfurization process, the expected 3H-1,2-dithiol-3-one derivative was isolated with an 83% yield.

Tetrabutylammonium Fluoride for Anionic Ring-Opening Polymerization of N-Sulfonyl Aziridines

Wang H, et al. European Polymer Journal, 2020, 140, 109999.

Tetrabutylammonium fluoride (TBAF) has been demonstrated to be an efficient initiator in the anionic ring-opening polymerization (AROP) of N-sulfonyl aziridines, particularly in the polymerization of 2-methyl-N-tosylaziridine (TsMAz). The general experimental procedure involved carrying out the polymerization under an inert argon atmosphere at 50°C. TBAF, initially dissolved in tetrahydrofuran (THF), was added to a flame-dried Schlenk flask, and the solvent was removed under reduced pressure. Following this, a solution of the monomer in dimethylformamide (DMF) was introduced into the reaction flask within a glovebox. The reaction mixture was then heated to 50°C and stirred, with polymerization progressing over a specific time period. The reaction was quenched by adding acetic acid and excess methanol, and the resulting precipitate was isolated and analyzed using Nuclear Magnetic Resonance (NMR) and Size Exclusion Chromatography (SEC).

Tetrabutylammonium Fluoride for Diazo-Diazo Cross-Coupling Reactions

Barik D, et al. Organic Letters, 2025.

In the study, tetrabutylammonium fluoride (Bu₄NF) was employed as a critical promoter to facilitate novel diazo-diazo cross-coupling processes. Specifically, Bu₄NF (1.5 equiv) was used to promote the coupling between thermally generated diarylketenes, formed from the rearrangement of α-aryldiazo ketones, and vinyldiazo esters acting as nucleophiles. This fluoride source effectively activated the reaction pathway leading to the formation of highly substituted pyrazole derivatives, distinct from the gold-catalyzed cyclopentenone products. The use of Bu₄NF enabled efficient nucleophilic attack by the vinyldiazo esters, thereby demonstrating its utility in promoting selective and divergent diazo-diazo cross-coupling reactions under mild conditions.

Tetrabutylammonium Fluoride for the Colorimetric Differentiation of Anions Using 1-(4-nitrophenyl)-3-((pyridin-4-yl)methyl)thiourea

Tarai A, et al. Inorganica Chimica Acta, 2017, 464, 108-113.

Tetrabutylammonium fluoride (TBAF) was utilized in a selective colorimetric detection system based on its interaction with 1-(4-nitrophenyl)-3-((pyridin-4-yl)methyl)thiourea (L). Although both TBAF and tetrabutylammonium acetate exhibited absorption maxima at 479 nm upon interaction with L, distinct differences in color intensity allowed for their discrimination in solution. To develop a practical detection platform, a solid-phase sensing system was fabricated by preparing a silica-supported form of L. Specifically, 2 g of silica (60-120 μm) was stirred in 20 mL methanol with L (10 mL, 10⁻³ M in methanol-DMF), followed by solvent removal under reduced pressure to yield a yellow, freely flowing powder. For testing, 30 mg of this L-silica composite was introduced to 10⁻³ M DMSO solutions of TBAF or tetrabutylammonium acetate. The presence of TBAF triggered a visible yellowish-brown color change, attributable to fluoride-induced anion formation with extended conjugation. Spectroscopic and ¹H NMR analyses revealed that fluoride interaction with L was irreversible beyond a 0.5:1 ratio, contrasting with reversible acetate binding forming a 1:1 hydrogen-bonded adduct. Moreover, fluoride liberated hydrofluoric acid, which reacted with the silica support to generate a hexafluorosilicate salt of L, subsequently isolated and characterized.