327-54-8

Basic information

• Product Name: 1,2,4,5-Tetrafluorobenzene
• Synonyms: 2,3,5,6-Tetrafluorobenzene;benzene,1,2,4,5-tetrafluoro-;p-Tetrafluorobenzene;1,2,4,5-TETRAFLUOROBENZENE;1,2,4,5-TETRAFLUOROBENZENE, 99+%;1,2,4,5-Tetrafluorobenzene 99%;1,2,4,5-Tetrafluorbenzol;1,2,4,5-Tetrafluorobenzene,98%
• CAS NO: 327-54-8
• Molecular Formula: C₆H₂F₄
• Molecular Weight: 150.07
• EINECS: 206-319-3
• Product Categories: Aryl;C6;Halogenated Hydrocarbons
• Mol File: 327-54-8.mol
• Article Data: 52

Chemical Properties

• Melting Point: 4 °C(lit.)
• Boiling Point: 90 °C(lit.)
• Flash Point: 61 °F
• Appearance: Clear colourless liquid
• Density: 1.344 g/mL at 25 °C(lit.)
• Vapor Pressure: 64.2mmHg at 25°C
• Refractive Index: n20/D 1.407(lit.)
• Storage Temp.: Flammables area
• Water Solubility: Not miscible or difficult to mix in water.
• BRN: 1909052
• CAS DataBase Reference: 1,2,4,5-Tetrafluorobenzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1,2,4,5-Tetrafluorobenzene(327-54-8)
• EPA Substance Registry System: 1,2,4,5-Tetrafluorobenzene(327-54-8)

Safety Data

• Hazard Codes: F,Xi
• Statements: 11-36/37/38
• Safety Statements: 16-26-36/37/39-37/39-33-7/9
• RIDADR: UN 1993 3/PG 2
• WGK Germany: 3
• HazardClass: 3
• PackingGroup: II
• Hazardous Substances Data: 327-54-8(Hazardous Substances Data)

Usage

Description

1,2,4,5-Tetrafluorobenzene is an aromatic compound with the chemical formula C6H2F4. It is characterized by the presence of four fluorine atoms attached to a benzene ring, resulting in unique chemical and physical properties. 1,2,4,5-Tetrafluorobenzene exhibits high thermal stability, low reactivity, and strong electron-withdrawing effects, making it a versatile building block in various chemical reactions and applications.

Uses

Used in Organic Synthesis:
1,2,4,5-Tetrafluorobenzene is used as an intermediate in organic synthesis for the production of various fluorinated compounds. Its strong electron-withdrawing nature and stability make it a valuable precursor for the synthesis of pharmaceuticals, agrochemicals, and specialty chemicals.
Used in Pharmaceutical Industry:
1,2,4,5-Tetrafluorobenzene is used as a pharmaceutical intermediate for the development of new drugs and drug candidates. Its unique properties allow for the creation of novel molecular structures with potential therapeutic applications, including the treatment of various diseases and disorders.

Synthesis Reference(s)

The Journal of Organic Chemistry, 29, p. 3042, 1964 DOI: 10.1021/jo01033a061

InChI:InChI=1/C6H2F4/c7-3-1-4(8)6(10)2-5(3)9/h1-2H

Upstream product

• 367-34-0 2,4,5-trifluoroaniline 
• 95-94-3 1,2,4,5-tetrachlorobenzene 
• 363-72-4 Pentafluorobenzene 
• 75410-99-0 1,2,4,5-tetrafluorobicyclo<2.2.0>hexa-2,5-diene 
• 23657-35-4 1,2,3,4,5,6-hexafluoro-7,8-diazatricyclo<4.3.0.0^2,5>nona-3,7-diene 
• 71-43-2 benzene 
• 392-56-3 Hexafluorobenzene 
• 355-68-0 perfluorocyclohexane 
• 372-18-9 1,3-Difluorobenzene 
• 367-11-3 ortho-difluorobenzene 
• 75-77-4 chloro-trimethyl-silane 
• 1559-88-2 1-bromo-2,3,5,6-tetrafluorobenzene 
• 5243-24-3 3-iodo-1,2,4,5-tetrafluorobenzene 
• 344-03-6 1,4-dibromotetrafluorobenzene 

Downstream Products

• 344-03-6 1,4-dibromotetrafluorobenzene 
• 392-57-4 1,4-diiodo-2,3,5,6-tetrafluorobenzene 
• 327-55-9 2,5-Difluoro-1,4-benzoquinone 
• 377-69-5 1,2,3,4,5,6-hexachloro-1,2,4,5-tetrafluoro-cyclohexane 
• 16956-91-5 2,3,5,6-tetrafluorophenylene-1,4-bis(trimethylsilane) 
• 53104-19-1 N-tert-Butyl-N-(2,3,5,6-tetrafluoro-phenyl)-hydroxylamine 
• 6257-03-0 2,3,5,6-tetrafluoro-4-nitrobenzene 
• 3828-42-0 1,4-Di-H-hexafluoro-1,4-cyclohexadiene 
• 1846-35-1 1,2,4,5-Tetrakis(methylthio)benzene 
• 76980-93-3 1,2,3,4,5,7-Hexafluoro-6-methyl-8-(2,3,5,6-tetrafluoro-phenyl)-naphthalene 
• 76980-92-2 1,2,3,4,6,8-Hexafluoro-5-(2,3,5,6-tetrafluoro-phenyl)-naphthalene 
• 5006-38-2 1,2,4-trifluoro-5-methoxybenzene 
• 121088-15-1 2,4,5-trifluoro-1-t-butoxybenzene 
• 96631-24-2 1-Ethoxy-2,4,5-trifluoro-benzene 

Relevant articles and documents

Study of the decarboxylation mechanism of fluorobenzoic acids by strong N-bases

The kinetics of the decarboxylation reactions of pentafluorobenzoic and tetrafluorobenzoic acids by various N-bases were studied using 19F NMR spectroscopy. The rate constants of these reactions are dependent on the structure of the fluorinated acid and the pKa values of the N-bases. Pentafluorobenzoic acid is decarboxylated about two orders of magnitude faster than tetrafluorobenzoic acid. With increasing pKa values of the protonated N-bases these reactions became much slower. These results suggested that the rate-determining step of the studied reactions is the attack of the conjugated acid (protonated N-base) on carboxylate anion. Copyright

Competition of Nucleophilic Aromatic Substitution, σ-Bond Metathesis, and syn Hydrometalation in Titanium(III)-Catalyzed Hydrodefluorination of Arenes

Several functionalized and non-functionalized perfluoroarenes were catalytically transformed into their para-hydrodefluorinated products by using catalytic amounts of titanocene difluoride and stoichiometric amounts diphenylsilane. Turnover numbers of up to 93 were observed. Solution density functional theory calculations at the M06-2X/TZ(PCM)//M06-2X/TZ(PCM) level of theory provided insight into the mechanism of TiIII-catalyzed aromatic hydrodefluorination. Two different substrate approaches, with a Ti–F interaction (pathway A) and without a Ti–F interaction (pathway B), are possible. Pathway A leads to a σ-bond metathesis transition state, whereas pathway B proceeds by means of a two-step mechanism through a syn-hydrometalation intermediate or through a Meisenheimer intermediate. Both pathways are competitive over a broad range of substrates.

NHC·Alane Adducts as Hydride Sources in the Hydrodefluorination of Fluoroaromatics and Fluoroolefins

We present herein the utilization of NHC-stabilized alane adducts of the type (NHC)·AlH3 [NHC = Me2Im (1), Me2ImMe (2), iPr2Im (3), iPr2ImMe (4), Dipp2Im (5)] and (NHC)·AliBu2H [NHC = iPr2Im (6), Dipp2Im (7)] as novel hydride transfer reagents in the hydrodefluorination (HDF) of different fluoroaromatics and hexafluoropropene. Depending on the alane adduct used, HDF of pentafluoropyridine to 2,3,5,6-tetrafluoropyridine in yields of 15–99 % was observed. The adducts 1, 2, and 5 achieved a quantitative conversion into 2,3,5,6-tetrafluoropyridine at room temperature immediately after mixing the reactants. Studies on the HDF of fluorobenzenes with the (NHC)·AlH3 adducts 1, 3, and 5 and (Dipp2Im)·AliBu2H (7) showed the decisive influence of the reaction temperature on the H/F exchange and that 135 °C in xylene afforded the best product distribution. Although the HDF of hexafluorobenzene yielded 1,2,4,5-tetrafluorobenzene in moderate yields with traces of 1,2,3,4-tetrafluorobenzene and 1,2,4-trifluorobenzene, pentafluorobenzene was converted quantitatively into 1,2,4,5-tetrafluorobenzene, with (Dipp2Im)·AliBu2H (7) showing the highest activity and reaching complete conversion after 12 h at 135 °C in xylene. The HDF of hexafluoropropene with (Me2Im)·AlH3 (1) occurred even at low temperatures and preferably at the CF2 group with the formation of 1,2,3,3,3-pentafluoropropene (with 0.4 equiv. of 1) or 2,3,3,3-tetra-fluoropropene (with 0.9 equiv. of 1) as the main product.

Decisive steps of the hydrodefluorination of fluoroaromatics using [Ni(NHC)2]

The hydrodefluorination reaction of perfluorinated arenes using [Ni 2(iPr2Im)4(COD)] (1; iPr2Im = 1,3-bis(isopropyl)imidazolin-2-ylidene) as a catalyst as well as stoichiometric transformations to elucidate the decisive steps for this reaction are reported. The reaction of hexafluorobenzene with 5 equiv of triphenylsilane in the presence of 5 mol % of 1 affords 1,2,4,5-tetrafluorobenzene after 48 h at 60 °C and 1,4-difluorobenzene after 96 h at 80 °C; the reaction of perfluorotoluene and 5 equiv of Et 3SiH for 4 days at 80 °C results in the selective formation of 1-(CF3)-2,3,5,6-C6F4H. Stoichiometric transformations of the complexes cis-[Ni(iPr2Im) 2(H)(SiPh3)] and cis-[Ni(iPr 2Im)2(H)(SiMePh2)] with hexafluorobenzene at room temperature lead to the formation of trans-[Ni(iPr 2Im)2(F)(C6F5)] (2) and trans-[Ni(iPr2Im)2(H)(C6F 5)] (4) with elimination of the corresponding silane or fluorosilane. The reactions of the C-F activation products trans-[Ni(iPr 2Im)2(F)(C6F5)] (2) and trans-[Ni(iPr2Im)2(F)(4-(CF3)C 6F4)] (3) with PhSiH3 and Ph 2SiH2 afford the hydride complexes trans-[Ni( iPr2Im)2(H)(C6F5)] (4) and trans-[Ni(iPr2Im)2(H)(4-(CF 3)C6F4)] (5), which convert into the compounds trans-[Ni(iPr2Im)2(F)(2,3,5,6-C 6F4H)] (7), trans-[Ni(iPr2Im) 2(F)(3-(CF3)-2,4,5-C6F3H)] (9a), and trans-[Ni(iPr2Im)2(F)(2-(CF 3)-3,4,6-C6F3H)] (9b), respectively. In the case of the rearrangement of trans-[Ni(iPr2Im) 2(H)(4-(CF3)C6F4)] (5) the intermediate [Ni(iPr2Im)2(η2-C, C-(CF3)C6F4H)] (8) was detected. Reaction of 8 with perfluorotoluene gave the C-F activation product trans-[Ni( iPr2Im)2(F)(4-(CF3)C 6F4)] (3). All these experimental findings point to a mechanism for the HDF by [Ni(iPr2Im)2] via the "fluoride route" involving C-F activation of the polyfluoroarene, H/F exchange of the resulting nickel fluoride, reductive elimination of the polyfluoroaryl nickel hydride to an intermediate with a η2-C,C- coordinated arene ligand, subsequent ligand exchange with the higher fluorinated polyfluoroarene, and renewed C-F activation of the polyfluoroarene. Without additional reagents, [Ni(iPr2Im)2(η 2-C,C-(CF3)C6F4H)] (8) rearranges to the isomers trans-[Ni(iPr2Im)2(F)(3-(CF 3)-2,4,5-C6F3H)] (9a; major) and trans-[Ni(iPr2Im)2(F)(2-(CF3)-3,4,6- C6F3H)] (9b; minor) in a ratio of 80:20. DFT calculations performed on conversion of trans-[Ni(iPr2Im) 2(H)(4-(CF3)C6F4)] 5 into the two products trans-[Ni(iPr2Im)2(F)(3-(CF 3)-2,4,5-C6F3H)] 9a and trans-[Ni( iPr2Im)2(F)(2-(CF3)-3,4,6-C 6F3H)] (9b) using the commonly accepted intramolecular concerted pathway via η2-C,F-σ-bound transition states predict 9b to be the major product. We thus propose that this reaction mechanism is not valid for the [Ni(NHC)2]-mediated C-F activation of partially fluorinated arenes with special substitution patterns.

Catalytic C-F bond hydrogenolysis of fluoroaromatics by [(η5-C5Me5)RhI(2,2′-bipyridine)]

A new class of efficient catalyst, the Rh(I) complex [(η5-C5Me5)RhI(bpy)] (1; bpy = 2,2′-bipyridine), for the C-F bond hydrogenolysis of fluoroaromatics (C6F5CF3, C6F6, C6F5H, and C6F5CH3) is presented. The best turnover number of 380 for C6F6 is afforded by using 0.1 mol % of 1, 0.8 MPa of H2, and 2 equiv of Et2NH in CH3CN at 25 °C. The successful isolation of the C-F bond cleavage product [(η5-C5Me5)RhIII(bpy)(C6F5)](F) as a plausible intermediate of the catalytic hydrogenolysis of C6F6 by 1 is also described.

Catalyst-Free Hydrodefluorination of Perfluoroarenes with NaBH4

Presented is an economical means of removing fluorine from various highly fluorinated arenes using NaBH4. The procedure was adapted for different classes of perfluoroarenes. A novel isomer of an emerging class of organic dyes based on the carbazole phthalonitrile motif was succinctly synthesized in two steps from tetrafluorophthalonitrile, demonstrating the utility of the hydrodefluorination procedure. Initial exploration of the dye shows it to be photoactive and capable of facilitating contrathermodynamic styrenoid E/Z isomerization.

New catalytic systems with chemically fixed nickel complexes in the reactions of reductive activation of C-F bonds in ionic liquid media

The nickel complexes with bidentate nitrogen-containing ligands covalently bound to alkylimidazolium cations were obtained for the first time. By the example of the reaction of selective hydrodefluorination of hexafluorobenzene to pentafluorobenzene, it was shown that the catalytic systems ionic liquid - water - covalently bound nickel complex based on the obtained compounds are much more efficient with repeated use in comparison with unfixed nickel complexes. The decisive influence of the cationic fragment of the ionic liquid on the possibility of multiple use of nickel complexes has been established.