373-68-2

Basic information

• Product Name: Tetramethylammonium fluoride
• Synonyms: Tetramethylammonium Fluoridede;n,n,n-trimethyl-methanaminiufluoride;TETRAMETHYLAMMONIUM FLUORIDE;Tetramethylammoniumfluoride,20%AqueousSolution;Tetramethylammonium fluoride, anhydrous;Methanaminium, N,N,N-trimethyl-, fluoride;Tetramethylazanium fluoride;Tetramethylaminium·fluoride
• CAS NO: 373-68-2
• Molecular Formula: C₄H₁₂N*F
• Molecular Weight: 93.14
• EINECS: 206-769-0
• Product Categories: quarternary ammonium salts;Deprotecting Reagents;Fluoride Sources;Protection and Derivatization
• Mol File: 373-68-2.mol
• Article Data: 10

Chemical Properties

• Melting Point: 170°C (dec.)
• Appearance: /
• CAS DataBase Reference: Tetramethylammonium fluoride(CAS DataBase Reference)
• NIST Chemistry Reference: Tetramethylammonium fluoride(373-68-2)
• EPA Substance Registry System: Tetramethylammonium fluoride(373-68-2)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 26-36
• RIDADR: 2811
• WGK Germany: 3
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 373-68-2(Hazardous Substances Data)

Usage

Description

Tetramethylammonium fluoride (TMAF) is a quaternary ammonium salt with the chemical formula (CH3)4NF. This hygroscopic white solid serves as a source of "naked fluoride," which refers to fluoride ions not bound to a metal atom in a complex. TMAF is historically prepared through two main approaches: (i) neutralization of tetramethylammonium hydroxide (TMAOH) with hydrofluoric acid (HF), and (ii) metathesis reaction of different ammonium salts with inorganic fluoride sources such as potassium fluoride (KF) or cesium fluoride (CsF). Due to the high basicity of the fluoride anion, TMAF reacts slowly with acetonitrile, leading to its dimerization and co-crystallization.

Uses

1. Used in Organic Synthesis:
Tetramethylammonium fluoride is used as a reagent for the conversion of aryl phenols to aryl fluorides when combined with sulfuryl fluoride. This application is significant in the pharmaceutical and chemical industries, where aryl fluorides are valuable building blocks for various compounds.
2. Used in the Synthesis of Fluoro Aromatics:
TMAF is utilized as a reactant in the synthesis of fluoro aromatics via fluorodenitration reactions. This process is essential in creating fluorinated aromatic compounds, which have applications in various fields, including agrochemicals, pharmaceuticals, and materials science.
3. Used in the Synthesis of Sevoflurane:
Tetramethylammonium fluoride is employed in the synthesis of sevoflurane, a widely used inhalation anesthetic, through halogen-exchange fluorination in ionic liquids. This method offers a more environmentally friendly and efficient route to produce sevoflurane compared to traditional methods.
4. Used in the Synthesis of Fluorinated Poly(oxomolybdates):
TMAF is used as a reactant in the synthesis of fluorinated poly(oxomolybdates), which are important materials in the field of catalysis and energy storage.
5. Used in the Generation of Onium Amide Bases:
Tetramethylammonium fluoride can react with aminosilanes to generate onium amide bases in situ. These bases are useful for deprotonating heteroarenes, which are essential intermediates in organic synthesis and have applications in the pharmaceutical and chemical industries.
6. Used in the Halide-induced Ring Opening of 2-substituted Aziridinium Salts:
TMAF is utilized in the halide-induced ring opening of 2-substituted aziridinium salts, which is a crucial reaction in the synthesis of various organic compounds, including pharmaceuticals and agrochemicals.

InChI:InChI=1/C4H12N.FH/c1-5(2,3)4;/h1-4H3;1H/q+1;/p-1

Upstream product

• 75-57-0 tetramethlyammonium chloride 
• 75-59-2 tetramethyl ammoniumhydroxide 
• 1643-35-2 tetramethylammonium hydrogen difluoride 
• 616-38-6 carbonic acid dimethyl ester 
• 392-56-3 Hexafluorobenzene 
• 23237-02-7 tetramethylammonium cyanide 
• 1239907-95-9 [NMe₄][XeO(fluoride)3] 
• 7446-09-5 sulfur dioxide 
• 661-36-9 tetramethylammonium tetrafluoroborate 

Downstream Products

• 593-53-3 Methyl fluoride 
• 86747-85-5 Tetramethylammonium methyl 4,6-O-benzylidene-2-deoxy-2-fluoro-β-D-glucopyranoside 3-sulfate 
• 62263-15-4 Tetramethylammonium perfluoro-p-cresolat 
• 335-10-4 heptafluoro-isobutyric acid 
• 1584-03-8 perfluoro-2-methylpent-2-ene 
• 79723-02-7 monotetramethylammonium hydrogen phthalate 

Relevant articles and documents

Hydrogen bonding. Part 66. Further studies of the fluoride ion assisted dissolution of 1-methyl-4,5-dicarboxyimidazole: Absence of cation participation and stoichiometric considerations

Excess 1-methyl-4,5-dicarboxyimidazole (H2MDCI) dissolves into saturated solution in the presence of sodium fluoride, and precisely four F are required for each H2MDCI solubilized. To account for the apparent removal of two acidic hydrogens from H2MDCI in the presence of undissociated diacid we postulated strong complexation of Na+ by MDCI2-. We now find that the dissolution behavior of H2MDCI in the presence of either cesium or tetramethylammonium fluoride is identical to that with sodium fluoride. As cesium ion should bind weakly if at all to MDCI2-, and tetramethylammonium ion should not be bound, we conclude that the cation present plays no role in the fluoride ion assisted dissolution of H2MDCI. Analysis of dissolution stoichiometry and titration data suggests the possibility that two F- react with H2MDCI to form HMDCI+ and HF2/- and that two more F are required but do not act to abstract acid hydrogen.

Tetramethylammonium Fluoride Alcohol Adducts for SNAr Fluorination

Nucleophilic aromatic fluorination (SNAr) is among the most common methods for the formation of C(sp2)-F bonds. Despite many recent advances, a long-standing limitation of these transformations is the requirement for rigorously dry, aprotic conditions to maintain the nucleophilicity of fluoride and suppress the generation of side products. This report addresses this challenge by leveraging tetramethylammonium fluoride alcohol adducts (Me4NF·ROH) as fluoride sources for SNAr fluorination. Through systematic tuning of the alcohol substituent (R), tetramethylammonium fluoride tert-amyl alcohol (Me4NF·t-AmylOH) was identified as an inexpensive, practical, and bench-stable reagent for SNAr fluorination under mild and convenient conditions (80 °C in DMSO, without the requirement for drying of reagents or solvent). A substrate scope of more than 50 (hetero) aryl halides and nitroarene electrophiles is demonstrated.

A fluoride salt ion liquid synthetic method of the

The invention relates to the field of organic chemical synthesis, particularly a synthesis method of a fluoride salt ionic liquid. The method comprises the following steps: adding excessive hydrofluoric acid, ammonium fluoride or ammonium bifluoride into halogenated imidazole and other raw materials, stirring in a closed environment, heating to 50-70 DEG C, and sufficiently reacting for at least 3 hours to obtain a non-dewatered fluoride salt ionic liquid; detecting, purifying and dewatering to obtain a thick liquid; and detecting the thick liquid to obtain the qualified fluoride salt ionic liquid. The method has the advantages of simple technique, no organic solvent, no waste and high end product purity.